BCRF Announces Two New Board Members

 

BCRF is proud to announce the addition of two new members to its Board of Directors. Jerome Bettis and William S. Karol recently joined the Foundation’s esteemed board, which is co-chaired by Kinga Lampert and William P. Lauder.

Jerome Bettis is a Super Bowl Champion and Pro Football Hall of Fame running back who serves as an ESPN NFL analyst. Affectionately nicknamed “The Bus,” Jerome was the sixth all-time leading rusher during his 13-year career.

While philanthropic work has always been a priority for Jerome, his appointment to the BCRF Board of Directors stems from his personal connection to the cause. His mother Gladys was diagnosed with breast cancer in 2014.

Her treatment course coincided with his Super Bowl debut. Her last round of chemotherapy took place the week before the big game.

“She was so strong, such a trooper. I was so proud of how she handled the whole thing. That’s where my strength comes from – my mom,” Jerome said.

Today Gladys is in remission. Since her treatment ended, Jerome and Gladys have hosted events to raise funds and awareness about breast cancer treatment and research. As one of the newest members of the Board of Directors, he’s proud to support game-changing research to help more families like his.

“One in eight women will be diagnosed with breast cancer in her lifetime, and if we can prevent that –help save a life – then it’s all worth it. More knowledge means more hope, a better chance of defeating breast cancer once and for all. We can beat this thing, but not without medical research,” he said.

William (Bill) S. Karol founded the investment firm KODA in 1989, where he still serves as President and Chief Executive Officer. Bill serves on several corporate boards, and was active in the Young Presidents’ Orgnaization Inc., holding several positions, including Chairman of the New England Chapter and chairman of multiple international events.

Bill and his wife, Sinesia, are Boston-based philanthropists who have been actively involved with BCRF for almost a decade. They have Co-Chaired the BCRF Boston Hot Pink Party since 2016 and Sinesia joined BCRF’s Advisory Board in July 2018. As a family, they are engaged with several charitable organizations and fundraising events, but breast cancer research remains a cause close to their hearts since Bill lost his first wife, Darcie, to the disease.

“Breast cancer interrupts and destroys so many women’s lives and has been devastating to my family and me. I can't think of a better way to solve this problem than to be involved with the Breast Cancer Research Foundation,” Bill said.

Bill previously served on the Board of Dana-Farber Cancer Institute (DFCI) for over 14 years. During that time, he created a research fund in honor of his late wife. He continues to serve as the DFCI Co-Chair of the Men’s Collaborative to Cure Women’s Cancer and was Co-Chair of the Basic Science Visiting Committee.

“The way breast cancer is treated today is so different than it was even 10 years ago. That's due to research that has uncovered so many breakthroughs,” Bill said. “BCRF has provided funds to some of the most important advances being used today. I look forward to helping BCRF in any way I can to achieve its mission.”

ASCO Annual Meeting 2019: Metastatic Breast Cancer Updates

 

The 55th annual meeting of the American Society of Clinical Oncology was held from May 31 through June 4 in Chicago. This year’s meeting included several updates in metastatic breast cancer research. Below are key highlights in this important field.

ER-positive/ HER2-negative breast cancer.  CDK4/6 inhibitors plus anti-estrogen therapy continue to demonstrate significant survival benefit in patients with hormone receptor-positive, HER2-negative advanced breast cancer.

Three CDK4/6 inhibitors, palbociclib (Ibrance®), ribociclib (Kiqali®), and  abemaciclib (Verzenio®) have been FDA-approved for treatment in combination with anti-estrogen (endocrine therapy) in post-menopausal women.

Two trials testing anti-CDK 4/6 drugs, ribociclib and palbociclib, respectively in patients with pre-menopausal advanced breast cancer showed that younger women received similar benefit from the anti-estrogen CDK4/6 combination as was reported for post-menopausal patients. Both drugs are approved for treatment in pre-menopausal women.

In discussing the presentations, BCRF investigator, Dr. Angelo De Leo, drew from previous studies to highlight that sensitivity to endocrine therapy may be driving the benefit of CDK4/6 inhibition. In previous studies of CDK4/6 inhibition, the greatest benefit was seen in patients whose tumors were sensitive to endocrine therapy.  In the current studies, women had not been previously treated with endocrine therapy, so their tumors would not have yet built up resistance. Ongoing studies are testing a biomarker that may be able to select patients most likely to benefit from this combination approach.

Triple negative breast cancer.  The Impassion 130 study was the first to show a significant benefit of the addition of immune-targeted therapy (atezolizumab) to chemotherapy in patients with advanced triple negative breast cancer (TNBC). At this year’s meetings, researchers reported updates from the study confirming earlier findings of extended benefit of immune therapy plus chemotherapy in this patient population.

In previous reports, BCRF investigator, Dr. Leisha Emens, explained the greatest benefit was seen in patients with PD-L1-positive tumors, specifically tumor infiltrating immune cells with high PD-L1, the molecular target of atezolizumab. An updated overall survival analysis reported at ASCO had a median of 18 months of follow up. Results from the second analysis were consistent with earlier findings.

Patients with PD-L1 positivity had median overall survival of 25 months with atezolizumab versus 18 months in similar patients who did not receive atezolizumab. The authors reported that the atezolizumab plus chemotherapy regime was generally well tolerated and side effects were well controlled. Patient surveys were similar between the two groups.

ASCO Annual Meeting 2019: Updates on Early Stage Breast Cancer

 

The ASCO Annual Meeting, held  from May 31- June 4 in Chicago, included more than 30,000 attendees which included specialists, patient advocates and industry representatives from the U.S. and around the world.

As more breakthroughs continue to be unveiled, researchers aim to refine their findings to help physicians and patients make decisions tailored to their type of breast cancer.  At this year’s meeting, updates from groundbreaking studies on early stage breast cancer were presented.

ER-positive/ HER2-negative breast cancer.

At last year’s ASCO Annual Meeting, the TAILORx clinical trial made headlines. The trial, supported in part by BCRF, revealed that 70 percent of women diagnosed with early-stage breast cancer could forego chemotherapy (opting for anti-estrogen therapy alone).

These finding were based on recurrence score results from the Oncotype DX® test, a blood test for early stage breast cancer patients may undergo. If a patient received a score that was low (0-10) or intermediate (11-25), the study found no added benefit of chemotherapy. However, the results were less clear for women under 50 with an intermediate Oncotype Dx® recurrence score of 16-25, for whom chemotherapy reduced the risk of recurrence.

This year researchers shared updates from the TAILORx trial bringing clarity to predicting risk of breast cancer recurrence in women under 50. In a secondary analysis, the investigative team sought to determine whether integration of recurrence score and clinical risk stratification – where the patient’s tumor size and histologic grade were taken into consideration – could help identify premenopausal women who might stand to benefit from more aggressive anti-estrogen therapy, such as ovarian suppression.

The analysis showed that for women under 50 with a recurrence score of 16-15, the addition of clinical risk stratification improved risk prediction. The clinical assessment did not improve risk prediction in low or high recurrence risk categories or in post-menopausal women. You can watch this short video with TAILORx lead investigator and BCRF researcher, Dr. Joseph Sparano discussing the results.

HER2-positive breast cancer. With the success of targeted therapies, HER2-positive breast cancer is now a treatable disease with several options. The standard approach includes neoadjuvant (pre-surgical) chemotherapy with one or more HER2-targeted therapies. Additional therapy after surgery includes chemotherapy plus HER2-directed therapy to reduce the risk of recurrence. For patients who show a pathological complete response (PCR) after neoadjuvant therapy, less therapy may be warranted.

In clinical trials, PCR  after neoadjuvant therapy (no residual tumor at time of surgery) is often used as a prognostic marker and predictor of outcome. Questions remain however, on how residual disease after neoadjuvant therapy should guide subsequent adjuvant therapy.

This was illustrated by results presented from the  KRISTINE trial, a phase III, randomized trial, which compared T-DM1 (trastuzumab emtansine) plus pertuzumab —a HER2-targeted regimen that omits standard chemotherapy—with the standard regimen of docetaxel, carboplatin, trastuzumab, and pertuzumab. Presenting the final analysis from the trial Dr. Sarah Hurvitz, University of California, Los Angeles, noted that patients with residual tumor cells after neoadjuvant therapy  were equally like to experience disease progression regardless of the type of subsequent adjuvant therapy. She summarized that while no benefit was seen with TDM-1 without chemotherapy, patients reported less toxicity  when compared with standard treatment.

In discussing results from KRISTINE and other ongoing clinical trials in early stage, HER2-positive breast cancer, BCRF investigator, Dr. Mark Pegram stressed the challenges and opportunities in understanding the biology of the residual tumor to guiding subsequent adjuvant therapy, which may or may not include chemotherapy. Some large tumors may be good responders, he noted,  but because of their initial mass, may not be completely eliminated by neoadjuvant therapy. These patients may do well to continue of HER2-directed therapy alone.

In other cases, the cells left behind after neoadjuvant therapy may be resistant  to continued HER2 treatment.  Understanding how to tell which the case is, is important to the patient and doctor in treatment decisions.  “The burden is on us,” Dr. Pegram noted, “to identify molecular, genetic, imaging markers to identify patients who are most suitable for consideration of de-escalation strategies with T-DM1 or newer HER2 antibody-drug conjugates.”

ASCO Annual Meeting 2019: Focus on Data Sharing

 

When ASCO president and BCRF investigator, Dr. Monica Bertagnolli delivered her presidential address to the 32,000 plus attendees at the 55th annual ASCO meeting, she challenged the audience of oncologists and oncologists in training to imagine a world where every patient’s treatment informed a future patient’s care. 

“What if the next time you and your patient had a challenging treatment decision to make,” she said, “you could draw on the experiences of everyone in the room?”

Choosing the theme of  “Caring for Every Patient, Learning from Every Patient” for this year’s meeting, Dr. Bertagnolli stressed that the key to learning from every patient is having patient data accessible to other doctors who can use it to inform their treatment discussion with their patients.

Data sharing was a major pillar of the National Cancer Moonshot to accelerate discoveries to improve outcomes for cancer patients. The adoption of the electronic health records (EHR), now utilized by 90 percent of US physicians, was a key component of that vision. Dr. Bertagnolli pointed to significant challenges that impede progress, including  the lack of standardization in terms and quality of data across EHR that make data sharing complex and interpretation uncertain. Efforts by ASCO include CancerLinQ and mCODE.

Assuring patient privacy and security and obtaining appropriate patient consent for access to information in electronic medical records is a critical component in the success of learning from one patient to benefit another patient.

Want to learn more about this year’s ASCO Annual Meeting? Below are other blogs covering the conference.

BCRF Researchers Honored at ASCO Annual Meeting

Updates on Early Stage Breast Cancer

Metastatic Breast Cancer Updates

Investigating Breast Cancer: Dr. Luca Gianni

 

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In this important and engaging conversation, Dr. Luca Gianni remains grateful to his mentor – Dr. Gianni Bonadonna – who brought him into the National Institute for the Study and Treatment of Cancer in Milan, Italy some 40 years ago. Based on what he learned there, Dr. Gianni has since delivered numerous breakthroughs in cancer research.

One involved finding ways to introduce therapies – to treat tumors before a main treatment – particularly in women with locally advanced or inflammatory HER2-positive breast cancer.

Now he is taking that same mindset – focus on early treatment – to drive his research in an important different direction: To help identify triple negative breast cancer patients most likely to benefit from checkpoint inhibitor therapy before beginning the treatment and those who will do well with chemotherapy alone. Not only would this help find patients with greater likelihood for an improved outcome, of course, but it also could help reduce the extreme costs and toxicity side effects for patients unlikely to benefit.

Dr. Gianni is Director of the Department of Medical Oncology and the head of the Project of Development of New Drugs and Innovative Therapies in Solid Tumors at the San Raffaele Scientific Institute in Milan. He is also Cofounder and President of the Michelangelo Foundation, a non-profit organization designed to advance research in oncology, and chairman of the Michelangelo Breast Cancer Study Group. Dr. Gianni has received several grants and research support, and was awarded the “Gianni Bonadonna Award and Fellowship” by the American Society of Clinical Oncology in 2011 – an award named after his mentor. He also has been a BCRF Investigator since 2018.


Read the transcript below:

Chris Riback: I’m Chris Riback. This is Investigating Breast Cancer, the podcast of the Breast Cancer Research Foundation and conversations with the world’s leading scientists studying breast cancer prevention, diagnosis, treatment, survivorship and metastasis.

You likely know the expression, Pay It Forward. It’s an important concept for any kind of social awareness, but it can carry special meaning as well in the breast cancer world, particularly in research.

That’s because so much of today’s important breakthroughs are built not only on yesterday’s participation of other patients, but, of course, the work of other researchers. 

It’s a sentiment Dr. Luca Gianni not only knows well, but also puts into practice every day.

As you’ll hear, in this important and engaging conversation, Dr. Gianni remains grateful to his mentor – Dr. Gianni Bonadonna – who brought him into the National Institute for the Study and Treatment of Cancer in Milan, Italy some 40 years ago. Based on what he learned there, Dr. Gianni has since delivered numerous breakthroughs in cancer research.

One involved finding ways to introduce therapies – to treat tumors before a main treatment – particularly in women with locally advanced or inflammatory HER2-positive breast cancer.

Now he is taking that same mindset – focus on early treatment – to drive his research in an important different direction: To help identify triple negative breast cancer patients most likely to benefit from checkpoint inhibitor therapy before beginning the treatment and those who will do well with chemotherapy alone. Not only would this help find patients with greater likelihood for an improved outcome, of course, but it also could help reduce the extreme costs and toxicity side effects for patients unlikely to benefit.

More about Dr. Gianni: He is Director of the Department of Medical Oncology and the head of the Project of Development of New Drugs and Innovative Therapies in Solid Tumors at the San Raffaele Scientific Institute in Milan. He is also Cofounder and President of the Michelangelo Foundation, a non-profit organization designed to advance research in oncology, and chairman of the Michelangelo Breast Cancer Study Group. Dr. Gianni has received several grants and research support, and was awarded the “Gianni Bonadonna Award and Fellowship” by the American Society of Clinical Oncology in 2011 – yes, an award named after his mentor. He also has been a BCRF Investigator since 2018.

I connected with Dr. Gianni in his lab in Italy, which left me envious of course that the conversation occurred, as you’ll hear, via computer, rather than in person – say, in a local Milan cafe… Well, we can’t have everything

Chris Riback:    Dr. Gianni, thanks for joining me. I appreciate your time. I'd like to start this conversation with history. After all, you're in Italy, a country rich with incredible his story. You're also cofounder and president, among other things of the Michelangelo Foundation. That certainly feels to me like a nod towards history, so I assume you have no problem with history, correct?

Dr. Luca Gianni: Well, I have little problems with history, but the name of the Michelangelo Foundation was not because of Michelangelo. It was a much less emphatic reason for that. The first meeting of the foundation was in a hotel that was the Michelangelo Hotel, so we picked that up.

Chris Riback: Okay, well but I would think perhaps the Michelangelo Hotel was named with the historical nod.

Dr. Luca Gianni: Absolutely.

Chris Riback:    Somewhere.

Dr. Luca Gianni: Absolutely.

Chris Riback: It's a good thing, I guess, that you did not have that meeting in a hotel with a silly name, and then ended up with a foundation with a silly name. At least you were in a hotel with a very-

Dr. Luca Gianni: Maybe we would have reverted it to the Michelangelo for some odd reason.

Chris Riback:    I'm sure that you would have. The history though that I really want to ask you about, of course, is your own. Specifically, much of your early career work helped identify neoadjuvant therapies, particularly in women with locally advanced or inflammatory HER2-positive breast cancer. I want to really understand that, because what I'm believing, and we'll get into this, and you'll correct me if I'm wrong, is that so much of your early work helped inform the work that you subsequently did and that you are doing now. So just to begin, what are neoadjuvant therapies, and why were those discoveries so significant?

Dr. Luca Gianni: Well, it is a very difficult question, especially to explain. A neoadjuvant in simple words is applying drugs before the application of surgery, rather than as an adjuvant after the surgery. In principle, it's a simple swap of timelines, so you start with one of the ingredients of the ideal type of therapeutic approach instead of the combination or one which has seen for many years as the surgical approach.

Dr. Luca Gianni: The history goes that a time ago, it was very frequent to observe women with very advanced breast cancer at first diagnosis, and so advanced that the surgeon couldn't apply a clean type of surgery. By clean surgery, you mean a surgery where the margins were free of tumor cells. So those were the years when the first effect chemotherapeutic combinations were made available. The idea was, "Okay, let's try with effective drugs first and see if we can shrink the tumor to a size where the surgeon can kick in and do his job at his best. So that the origin of the neoadjuvant approach.

Chris Riback: Is there something about your mindset, your thinking, your scientific approach that had you focus on the period before the surgery? As we get into the work that you are doing, in terms of the scoring and your immune-based gene score work, and we'll talk about that in a moment, but it was feeling to me, in looking at your history and looking at the work that you do, that a lot of your focus is on, "How do we address things early, or as early as possible? How do we work in advance of some other event?" Am I interpreting your approach correctly?

Dr. Luca Gianni: You have a correct interpretation. What is my real drive is to try and apply what we have, at this best, in controlled conditions. If I apply the drugs before surgery, I can investigate and see what happens with drugs, and eventually change the drugs if the results are not as satisfactory as I want them to be for the benefit like the patient. While if I apply the drugs after the surgery, I basically am treating a condition where I am considering risk. The risk is not certainty. It is not something that they can measure. I can approach an estimate of risk, and if I apply the wrong type of drugs, I will know it only when there will be a relapse, and I don't want a relapse. If I apply them early, when I can measure "What did they do?" I can optimize the type of approach and the treatment.

Chris Riback: So let's talk about one of those conditions. It's one of the most challenging conditions, obviously, within the breast cancer world, and that's triple negative breast cancer. Not all triple negative breast cancer cases are responsive to immunotherapy, are they? The belief is that one factor impacting the ability to generate responsiveness is a lack of a biomarker to predict response to those therapies. Is that right? Talk to me about the challenges around potentially the lack of responsiveness to immunotherapy among some if not many triple negative breast cancer cases.

Dr. Luca Gianni: Okay. The topic is extremely complex, because immunotherapy has different possibilities of being the right answer according to many different thing, many variables, as we call them. First of all, we shouldn't be distracted by the relatively minor type of results with immunotherapy in metastatic breast cancer. We are now having a good feeling that, indeed, in metastatic disease, there are a number of down-regulation of immune systems that are not present at first diagnosis. If you speak about immunotherapy of triple negative breast cancer, recently there was a clear cut demonstration that in the neoadjuvant setting, the application of immunotherapy with chemotherapy affords potentially an outstanding rate of responses that have never been witnessed before.

Dr. Luca Gianni: So that tells us two things. Number one is that we should apply these drugs as early as possible. Number two, that maybe neoadjuvant, that is application before surgery, is better than adjuvant treatment. Why is that so? We think, and there are experiments going this direction, that if you apply immunotherapy as we have it with chemotherapy, in the presence of large burden of tumor, you have a higher chance of achieving kind of a vaccination against the tumor, and so the results tended to be much longer lasting than if you apply the same drugs after surgery when the tumor is almost nil or actually nil.

Chris Riback: What is the process? And I think this starts to get among the work that you're doing. What is our process for identifying which cases, which individuals are receptive to that vaccine, that prework that you've just described versus the ones that aren't, so that it's not being done ... randomly is not the right word, but so that it's being done with as much science and predictability as possible?

Dr. Luca Gianni: Okay. We have approached the problem in different ways. One way is that of designing specific particles so we use immunotherapy with chemotherapy prospectively as neoadjuvant and test for immune particles. That is one aspect. The other one is a different type of approach. In the past, when there was only chemotherapy around, we were already focusing our attention on immunology and in the value of the immune system in modulating the response of chemotherapy. We define and derived it from data available in literature that the expression of six genes associated with immune response was strongly associated with the probability of long-term survival without progression or relapse. We applied that to our patients, both in the adjuvant and in the neoadjuvant studies, and we observed that it worked. So our first approach is, okay, if it works, we needed to validate this finding, and if we validated this finding, we already have one major tool in our hands, because we will be able to identify those patients who are at very good chance of being cured by chemotherapy only.

Chris Riback: Is this the immune-based gene score, or is that-

Dr. Luca Gianni: Exactly.

Chris Riback: Yes.

Dr. Luca Gianni: This is an immune-based gene score. That will allow us to focus our attention on the remaining cases that they're not the type of probability, and try to modulate the immune response into these patients.

Chris Riback: My understanding is the benefits of this opportunity of the work that you're doing could be considered actually in two directions. One is positive direction, identifying the cases that perhaps have a higher probability of success, but then also in terms of managing the down-side risk, managing wasted cost, but even more significantly probably, saving people from having to deal with the toxicity when the process likely won't work for them anyhow. Is that right? Is it right to look at this bi-directionally?

Dr. Luca Gianni: You got it perfectly right. The point is that any additional drug is an addition of a potential source of toxicity. Drugs are very good, but drugs can be very toxic, so if I can avoid drugs, because they are not needed, that is a very important type of information. The other thing is that there are cases where I do need those drugs, and I want to know that positively, rather than giving the drug to 100% of the cases who come to my office, and causing many of them just the toxicity, and a lot of patients have no effect whatsoever, because they progress. I wanted to discriminate the effect of the drugs that they get. This is even more important in current oncology where many new drugs are so expensive that really challenge the financial possibilities of individuals.

Chris Riback: Yes, doing that prework, it could be very, very helpful on a number of fronts as you're identifying. How would you characterize where you are on this work? Are you where you thought you would be, where you would hope to be? Is there any aspect of it that you're finding particularly challenging, and you wish maybe you had Michelangelo around to help you think through the problem? How would you characterize where you are on your work?

Dr. Luca Gianni: Well, we are at mid-way, as it often happens. We have very good initial findings, and what we have done is to use a very good sample collections that we have done during the years in a couple of our trials. We have conducted in the past years, as the Michelangelo Group, two large trials of neoadjuvant approach, and we have now selected more than 350 patients with triple negative breast cancer, in whom we have available the tissue of the original diagnosis of the tissue, during the treatment, and whatever it was left at surgery. In addition to that, we have blood from them, so we started recently to perform a series of assays and tests to explore several aspects of the tumor and interpret the results, and apply our immune score in these patients. This is not immediate, but we now have the possibility of using this tool, which is very important.

Dr. Luca Gianni: To give you an example, since the collection of samples and the analysis of the trial have already been completed, we basically have the possibility of linking the immunoscore or the findings already to the results, to the intermediate results measured at surgery, and to the longer-term results, measured with continuous follow up. So although we have just started with these assays, we have the privilege of counting on the completed clinical trial done, and so we interpreted the results in a faster way than if we started today the collection of tumor.

Chris Riback: Earlier in this conversation, you indicated that one thing that you don't like, and nobody likes of course, is recurrence. Am I understanding you correctly that part of this work, or maybe it's adjacent work that you're doing, also can help identify various factors linked to the risk of recurrence?

Dr. Luca Gianni: Yes. Yes, this is exactly the point, because you know, we have a positive part, as you already said, which is identifying those who do not need anything more, because they already have a very high probability of being cured. On the other hand, we have the possibility of identifying those cases who unfortunately didn't reach that level, and do need more, and so apply to them more therapeutic opportunities that currently we have available, and do something that is more focused and more optimized for their needs.

Chris Riback: Dr. Gianni, what is it like doing this work in Italy? What is the culture there around breast cancer? Here in the United States, of course, it's obviously a very big deal, a very high level of awareness, maybe not about every medical detail, but certainly about the disease generally, the seriousness of it. Because it's affected so many people, there's a certain openness about discussion. Is that the case in Italy? What's the public consciousness like there around breast cancer?

Dr. Luca Gianni: Well, the consciousness is very deep. I would say that especially in the northern part of Italy, the approach is not very far and very different that in the United States. Also, in terms of awareness of the problem and adherence to the criteria for screening and so on and so forth. As it happens also in the United States where you have less privileged subgroups of population, also in Italy, we have groups of people who do not fully understand the relevance of screening and the importance of early diagnosis of breast cancer. But in general, the type of approach is not very far.

Dr. Luca Gianni: You have also to consider that we were very lucky. In Italy, we grew in terms of oncology under the guidance of giants of oncology such as Gianni Bonadonna, and for the surgical part, such as Umberto Veronesi. They were able to reach not only the doctors, but also the lay people, and make them understand how important it is to have an early diagnosis. So I think that Italy is, in this respect, a country where it's easy to work with the type of objectives that we have within Michelangelo and within my group.

Chris Riback: You just mentioned him. It's impossible to have a conversation with you without asking about the influence of Gianni Bonadonna on you. Now you come from a family of doctors. Your parents, I understand, were both doctors. So was it always going to be medicine of some sort for you, and then the work that you did with Bonadonna moved you towards research? Or were your parent pushing you towards the arts and literature and you rebelled against them and went into science instead?

Dr. Luca Gianni: No, my father was a prominent doctor in Italy, but he didn't want me to be a doctor. I decided to be a doctor, and my interest has always been in internal medicine and actually liver diseases. When I met Gianni Bonadonna, I met him by chance. Gianni Bonadonna had been working with my father when my father was senior staff at the University of Milan. So when he came back, Gianni Bonadonna came back from the United States, called up my father and said, "Well, I need young people to work in my new division, and would like to know, do you know anybody?" So my father said, "My son is here and he's an internist," and he asked me to go and speak with Gianni Bonadonna.

Dr. Luca Gianni: I went to Gianni and I said, "I'm not interested in oncology." Those were times when oncology patient had very terrible prognosis in front of them. They were late in making diagnosis, had no drugs and so on. "The only interest," I said to Gianni Bonadonna, "to come and work in oncology is if I had a chance to go in the United States and do research." So he said, "Well, I'd like people that do not sit on their back to make a career, so come on and I will send you to United States and do research." So that was my entrance door into the oncology field and into my acquaintance with Gianni Bonadonna.

Chris Riback: And then I read where, in 2011, the American Society of Clinical Oncology awarded you the Gianni Bonadonna Award and Fellowship. Given your relationship, and you know, I don't if he is still alive. I don't know, and if he did pass away, I don't know when that was, but that must have been extremely meaningful to you to win the award in his name.

Dr. Luca Gianni: Absolutely. It was absolutely incredible for me, and you know, Gianni had been really hit hard by a vascular hemorrhage, a cerebral hemorrhage, and so I took over all of his work and went on. Until then, I was working in oncology and new drug development, not in the breast field. So when they awarded me the Gianni Bonadonna prize, it was very emotional for me. Gianni Bonadonna was still alive then. He was as moved as I was when it was given to me. Gianni passed away in 2015, and we decided in Michelangelo to create a new nonprofit foundation dedicated to him. So now we have a Gianni Bonadonna Foundation just for innovating new drugs, doing something different from the Michelangelo, but it is something that we really care a lot about.

Chris Riback: That's a tremendous legacy. That's wonderful. To close out, BCRF, what role has BCRF played in your research?

Dr. Luca Gianni: BCRF is playing a key role. You know, we have been very good in making clinical trials and running clinical trials in a very resolute, innovative, and very reliable way, but we were missing the opportunity to run translation research. We had collected plenty of samples, but we had no possibility to go on with that beyond any given point. Breast Cancer Research Foundation is just looking to our deficit and saying, "We like it, and we support you," and does so in such a simplified way that our life is much easier than with any grant application that I ever had. So I am particularly grateful to Breast Cancer Research Foundation for this straight forward approach and support of all our science.

Chris Riback: Finally, a look to the future. I read a piece on you that starts, "According to Luca Gianni, everyone has a wish list of career milestones that feeds their dreams and ambitions." You have accomplished so much. What is the next career milestone that would feed your dreams and ambitions?

Dr. Luca Gianni: Well. Frankly, I would love to leave this intent and intenseness into people that they know that they can do something and accomplish something. Young people must be supported. You know, the future is with them, so my next goal is to maintain a tradition. I was supported by Gianni Bonadonna and others like him. I could name Larry Norton. I could name Gabriel Hortobagyi and plenty of friends that I met during my career. I think that I was an extremely lucky man, very fortunate to make these meetings and encounters. I would like to create the opportunities for other young and talented people to get the same good luck and support in their career. So that's my real goal for the future.

Chris Riback: Dr. Gianni, thank you. Thank you for your time, and thank you, of course, for the work that you have done and are doing.

Dr. Luca Gianni: Thank you very much for this chat. It was very pleasant.

Chris Riback: That was my conversation with Dr. Gianni. My thanks to Dr. Gianni for joining and you for listening. To learn more about breast cancer research or to subscribe to our podcast, go to bcrf.org/podcast.

BCRF Researchers Honored at ASCO Annual Meeting

 

The annual meeting of the American Society of Clinical Oncology is the largest clinical oncology meeting in the world. This year’s meeting, held from May 31-June 4 in Chicago, had more than 30,000 attendees which included clinical and laboratory scientists, professionals from every oncology specialty, trainees, patient advocates and representatives from the pharmaceutical industry. For five days, they listened to the latest reports on advances in clinical and laboratory research across the spectrum of cancer diseases.

In addition to research updates, each year ASCO’s committee members select awardees in a variety of categories of distinction. BCRF is proud to acknowledge members of its scientific leadership and researchers who were recognized at this year’s meeting.

Joan S. Brugge, PhD, BCRF Scientific Advisory Board Member

Dr. Brugge received the Science of Oncology Award and Lecture acknowledging her contributions to the understanding of tumorigenesis, including her seminal work in characterizing the development of normal breast and breast cancer cells.

Her recent research focuses on the development of treatment resistance and methods to overcome resistance. In her award presentation, Dr. Brugge explained how tumor cells adapt to the stresses of their cellular environment which influences drug resistance and tumor growth. This knowledge may fuel the discovery of potential therapeutic targets.  BCRF spoke to Dr. Brugge at the meeting. You can watch the Facebook live interview here.

Lisa A. Carey, MD was elected to the Fellows of ASCO. The Fellow of the American Society of Clinical Oncology (FASCO) distinction recognizes ASCO members for their extraordinary volunteer service, dedication, and commitment to ASCO. BCRF congratulates Dr. Carey for being elected to the FASCO and spoke with her during the meeting.  You can view the interview where she discusses the role of clinical trials in advancing care for patients here.

Judy E. Garber, MD, MPH, FASCO, Co-Scientific Director, BCRF.

Dr. Garber was honored with the ASCO-American Cancer Society Award and Lecture acknowledging her contributions toward cancer control and prevention, including her work in clinical cancer genetics, triple negative breast cancer, and the use of agents that target DNA repair defect. In her award talk, Dr. Garber spoke about the efforts made by her team and others to understand why some individuals are more likely to develop breast cancer, which individuals should be tested and how they should be counseled on test results, who is more likely to benefit from certain treatment strategies and how we’re starting to address the challenges of cancer prevention.  

Gabriel N. Hortobagyi, MD, MACP, FASCO, Chair of the BCRF Scientific Advisory Board.

Dr. Hortobagyi received the David A. Karnofsky Memorial Award and Lecture where he was honored as one of the world’s leading authorities on the management of breast cancer. In his award lecture, he highlighted key achievements over his illustrious career spanning nearly 50 years. Many of those achievements mark milestones in advances in the care and quality of life of breast cancer patients, beginning with the evolution of clinical trials, the discovery of new drug targets, and advent of neoadjuvant therapy, through the completion of the human genome project, which led to the molecular profiling of tumors and laid the foundation of precision medicine. “Research success, by definition is incremental,” he said. “You have to build on what you learn and take the information two steps further.”

Ann H. Partridge, MD, MPH, FASCO

Dr. Partridge was honored with the Ellen L. Stovall Award and Lecture for Advancement of Cancer Survivorship Care for her work on characterizing the unique issues that face younger women with breast cancer, including the impact of treatment on fertility, adherence with hormonal therapy, psychological impact, effects of treatment on sexual functioning, and the factors that play an important role in patient decision-making.

In her awards lecture titled, “The Art and Science of Cancer Survivorship” she acknowledged both the progress and challenges that remain in improving the care and quality of life for the growing number of cancer survivors. You can read more about Dr. Partridge’s BCRF work here and watch an interview with her recorded at the San Antonio Breast Cancer Symposium.

Lawrence N. Shulman, MD, FACP, FASCO

Dr. Shulman received the Humanitarian Award recognizing his work in the development and his leadership role in the establishment of national cancer treatment programs with the Ministries of Health in Rwanda and Haiti. BCRF had a chance to speak with Dr. Shulman about his work in Rwanda and the impact BCRF funding has had on its success. You can view the interview here.

Norman Wolmark, MD, FACS

Dr. Wolmark received the Gianni Bonadonna Breast Cancer Award and Lecture for his leadership of National Surgical Adjuvant Breast and Bowel Project (NSABP) Foundation, in advancing the field of breast cancer. In his award presentation, Dr. Wolmark presented 60 years of NSABP clinical trials that have led to changes in standards of care in the management of early breast cancer. This included early trials the showed no added benefit of radical mastectomy over breast conserving surgery with radiation. Later trials led to the retreat from chemotherapy in patients with a low risk of occurrence. Many ongoing trials are leading the way in precision medicine. 

The late Dr. Arti Hurria, MD, FASCO was honored at the ASCO Annual Meeting for her contributions in geriatric oncology. Dr Hurria, who tragically lost her life last fall in a car accident last year, was remembered throughout the ASCO meeting. BCRF acknowledged her commitment to mentoring the next generation with a merit award in her honor that provides travel costs for a young investigator in geriatric oncology to attend the meeting and present their research. In addition, the Conquer Cancer Foundation endowed a young investigator award in geriatric oncology that will bear her name.

Men’s Health Week: Male Breast Cancer Research Updates

 

Breast cancer is the most commonly diagnosed cancer in women and the second most common cause of cancer death in women. However, each year, more than 2,500 new cases of breast cancer are diagnosed in men, with 500 men dying from their disease each year.

Because male breast cancer is so rare, most men and their physicians do not consider breast cancer when they see or feel something unusual in the chest. This can result in a later diagnosis and higher risk of death.

The rare occurrence of breast cancer in men also makes it difficult to study as few men are available or even recruited to participate in clinical trials. That is beginning to change, as more trials are including men and there is an increased effort to understand the molecular and genomic landscape of male breast cancer.

BCRF was at the vanguard of this trend with its support of the International Male Breast Cancer Program, the largest study in the world on male breast cancer that was launched in 2006 and led by BCRF researchers Drs. Fatima Cardoso and Sharon Giordano. Because of this support we are learning more about this rare and understudied disease.

What we've learned

Male breast cancer is different from female breast cancer. In a retrospective analysis of 1,822 men with breast cancer, Dr. Cardoso and her colleagues reported that male and female breast cancers are different in terms of histology and grading. The study also showed that while over 90 percent of male patients had estrogen receptor (ER)-positive breast cancer, only 77 percent of them received endocrine therapy after surgery, which is the standard of care of ER-positive breast cancer

Male breast cancers are molecularly different from female breast cancer.  Breast cancer is classified into different subtypes based on molecular profiles of the tumors. A molecular profile is a snapshot of the genes or molecular programs that are promoting the tumor growth and can help to guide the appropriate treatment for each patient.

A molecular profiling analysis of 152 breast tumor samples from men identified five intrinsic subtypes of male breast cancer with various gene expression profiles. One of these subtypes has not been seen in women. Other research by BCRF investigators has also shown male breast cancers harbor different gene mutations than those found in female breast cancer.

Treatment of breast cancer in men. Most breast cancers in men are driven by estrogen, as are breast cancers in women. Treatment for men typically includes the antiestrogen drug tamoxifen along with surgery and radiation therapy. The recent approval of the CDK 4/6 inhibitors drug, Ibrance® (palbociclib) for men with advanced or metastatic breast cancer provides a new option for men with late-stage disease. Ongoing studies are uncovering potentially new targets for breast cancers in men, including unique mutations in the estrogen receptor gene not seen in female breast cancer.

What's next?

Since few men are enrolled in clinical trials, treatment recommendations are frequently based on the subtype of breast cancer alone. In the final phase of the International Breast Cancer Program, Dr. Cardoso’s team will initiate a clinical trial to test a combination hormone therapy in men with breast cancer. They will continue to conduct molecular profiling on the more than 500 tumor samples from the retrospective component of the study.

Because of increased awareness and the activity of male breast cancer advocates, the study of male breast cancer has increased, and research will continue to fuel discoveries that will lead to better outcomes in men with breast cancer.

Additional resources

American Cancer Society: Breast Cancer in Men

Male Breast Cancer Coalition: Patient support and resources

ASCO interview  with Dr. Giordano

BCRF Facebook Live interview with Dr. Cardoso

Investigating Breast Cancer: Dr. Susan Horwitz

 

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Can life change with a single letter in the mail? For my guest today, it did, and subsequently, so did the lives of millions of people with various forms of cancer, including breast cancer.

The letter in question came from the National Cancer Institute in 1977. The recipient was Dr. Susan Horwitz. The result: the creation of one of the most important cancer drugs that come from a natural product: Taxol, which is isolated from the yew plant. Today it is given to over a million patients.

As you’ll hear, Dr. Horwitz work – indeed, her incredible curiosity – didn’t end there. She has continued to investigate new cancer treatments that leverage natural products. Why?

Take triple negative breast cancer. By definition, it’s among the most challenging cancers to treat, comprising some 15-20 percent of all breast cancers. These aggressive tumors are treated with a cocktail of chemotherapy drugs. And although many patients have excellent survival following treatment, some patients with specific types of triple negative breast cancer have an incomplete response or even a relapse after a period of remission.

Making them even more difficult: Triple negative breast cancer tumors are frequently resistant – or become resistant – to a variety of drugs, increasing their potential to spread to other tissues – a process called metastasis.

To address these challenges, some scientists have screened novel chemotherapy drugs against triple negative cells to identify those with superior activity and less toxicity than conventional therapy. The goal: Find new therapeutic options -- new drug candidates – that they hope may lead to targeted therapies and new combination approaches to counter drug resistance and improve outcomes for patients with aggressive breast cancer.

How does this process work? What progress has been made? How hopeful do the outcomes seem? Dr. Horwitz is the one to ask.

Dr. Horwitz is a Distinguished University Professor and the Rose C. Falkenstein Chair in Cancer Research at the Albert Einstein College of Medicine in New York.

Among her many honors: The Warren Alpert Foundation Prize from Harvard Medical School; American Cancer Society's Medal of Honor; the American Association for Cancer Research Award for Lifetime Achievement in Cancer Research. Most recently, Dr. Horwitz earned the 2019 Canada Gairdner Award, the country’s highest scientific prize. She has served as president of the American Association of Cancer Research, and has been a member of The National Academy of Sciences, the Institute of Medicine of the National Academies, [the American Academy of Arts and Sciences, and the American Philosophical Society,] and others. She also has been a BCRF Investigator since 2007.


Read transcription below:

Chris Riback: I’m Chris Riback. This is Investigating Breast Cancer, the Podcast of the Breast Cancer Research Foundation and conversations with the world’s leading scientists studying breast cancer prevention, diagnosis, treatment, survivorship and metastasis.

Can life change with a single letter in the mail? For my guest today, it did, and subsequently, so did the lives of millions of people with various forms of cancer, including breast cancer.

The letter in question came from the National Cancer Institute in 1977. The recipient was Dr. Susan Horwitz. The result: The creation of one of the most important cancer drugs that come from a natural product: Taxol, which is isolated from the yew plant. Today it is given to over a million patients.

As you’ll hear, Dr. Horwitz work – indeed, her incredible curiosity – didn’t end there. She has continued to investigate new cancer treatments that leverage natural products. Why?

Take triple negative breast cancer. By definition, it’s among the most challenging cancers to treat, comprising some 15-20 percent of all breast cancers. These aggressive tumors are treated with a cocktail of chemotherapy drugs. And although many patients have excellent survival following treatment, some patients with specific types of triple negative breast cancer have an incomplete response or even a relapse after a period of remission.

Making them even more difficult: Triple negative breast cancer tumors are frequently resistant – or become resistant – to a variety of drugs, increasing their potential to spread to other tissues – a process called metastasis.

To address these challenges, some scientists have screened novel chemotherapy drugs against triple negative cells to identify those with superior activity and less toxicity than conventional therapy. The goal: Find new therapeutic options -- new drug candidates – that they hope may lead to targeted therapies and new combination approaches to counter drug resistance and improve outcomes for patients with aggressive breast cancer.

How does this process work? What progress has been made? How hopeful do the outcomes seem? Dr. Horwitz is the one to ask.

Dr. Horwitz is a Distinguished University Professor and the Rose C. Falkenstein Chair in Cancer Research at the Albert Einstein College of Medicine in New York.

Among her many honors: The Warren Alpert Foundation Prize from Harvard Medical School; American Cancer Society's Medal of Honor; the American Association for Cancer Research Award for Lifetime Achievement in Cancer Research. Most recently, Dr. Horwitz earned the 2019 Canada Gairdner Award, the country’s highest scientific prize. She has served as president of the American Association of Cancer Research, and has been a member of The National Academy of Sciences, the Institute of Medicine of the National Academies, [the American Academy of Arts and Sciences, and the American Philosophical Society,] and others. She also has been a BCRF Investigator since 2007.

This was a remarkable conversation, not only for the science discussed, but also the role Dr. Horwitz has played in its history.

Chris Riback: Dr. Horwitz, thanks for joining me, I appreciate your time.

Dr. Susan Horwitz:  It's my pleasure.

Chris Riback: To begin, congratulations. You were recently named one of seven winners of Canada's Gairdner Award. And by my reckoning, you're not even Canadian. That's quite an honor.

Dr. Susan Horwitz: I am not Canadian and it is quite an honor. I'm deeply honored.

Chris Riback: The president of the organization that nominated you, said, and I'm quoting, "Susan meticulously unraveled the mysteries of one of the world's most important cancer therapeutics." Do you think of yourself that way? As a sleuth? Do you feel like a medical detective, a scientific Miss Marple perhaps?

Dr. Susan Horwitz: Well that's exaggerating a little bit. But I do, in a way, think of these as puzzles. Trying to understand, as deeply as we can, how a drug acts to interact with a cancerous cell.

Chris Riback: So, let's talk about those drugs and that interaction and, you know, of course, having that conversation with you, it's impossible not to start that conversation with your Taxol work, which involves using natural products to develop treatments. Why natural products? How did get there? I know a little bit about it. I've read about this story but I'd love to hear it from you directly, because it sounds remarkable.

Chris Riback: Apparently one day in 1977, you got a letter, I believe it was, or perhaps a call but I think it was a letter, from the National Cancer Institute.

Dr. Susan Horwitz: That's correct. I received a letter from the National Cancer Institute requesting that I look at the mechanism of action of Taxol. I had never heard of Taxol, to be very honest, and there was only paper in the literature. So you certainly wonder why did the National Cancer Institute call and interact with me. Well, I've had a long-standing interest in natural products as a source of new drugs for the treatment of cancer. And when they had written to me, I had published on a number of natural products. And by natural products I mean compounds which are isolated from living organisms. That can be a tree, that can be a bush, that can be a sponge from the ocean, it can be from a bacteria. But those were the kinds of compounds I was interested in.

So, I think that's the reason that the National Cancer Institute wrote to me and as I say, there was only one paper in the literature and that was written by the two medicinal chemists, Drs. [Monroe] Wall and Mansukh Wani who had actually isolated this molecule from the bark of the tree Taxus brevifolia, which is the western yew. Many of us have this tree or bush, actually, in our gardens and that is where this drug originally came from. It was from large trees which grow on the west coast in Washington, Oregon, Northern California.

So when I got this drug, the first thing I, of course, looked at, was the structure. One thing about natural products is that they introduce structures that no chemist would sit down and synthesize. They're quite unusual. Taxol is what I call architecturally complex. It has many [boots] in it that aren't seen in other places, in other drugs.

So it was intriguing. And I had a new graduate student at the time, Peter Schiff, and I said, "Well, let's look at it. We'll look at it for a month and if it's interesting, you can use it as your thesis project. If nothing happens, we'll look for another thesis project." So that's how, really, I got into the drug. But after that one month, we knew we had something interesting.

Chris Riback: It was a heck of a month, wasn't it?

Dr. Susan Horwitz: It was!

Chris Riback: Why natural products? So it's interesting to me that you already had an interest in that aspect of research and of science and that that was kind of why the National Cancer Institute sent you a letter. I'm curious, do you happen to know? Did they send any other letters out and perhaps you were the first to respond? Or were you the only person they sent the letter to, to your knowledge?

Dr. Susan Horwitz: To my knowledge I was the only person they sent the letter to, but I really don't know, to be honest. Many people don't realize how important natural products are, in determining drugs.

Chris Riback: Explain that to me, please.

Dr. Susan Horwitz: Okay, so about 50% of the drugs that Americans take today, are either natural products, a derivative of natural products. Did you know Aspirin for example, which everyone takes some time in their life, for a variety of reasons, originally was from the Willow tree.

Chris Riback: No, did not know that.

Dr. Susan Horwitz: Penicillin, which really was so important, the Second World War and treating diseases, comes from a fungi. The pill which has changed our world, originated from yams in South America. So about 50% of the drugs we take, come from natural products. And I've always found that very fascinating and very interesting because it allows you to study not only the chemistry and the biology, but the botany and trying to understand why and how these natural products are produced. And of course, as we reduce our forests, the Amazon, we're probably getting rid of a lot of drugs which could be important.

Chris Riback: Do you think, was it your background in biology that potentially led you to have that interest in natural products, or was it something else about you or the way your mind words that drew you in that direction?

Dr. Susan Horwitz: Well, a lot of different things of course have come together. I was, when I was a graduate student, I was studying enzyme kinetics, and I thought I would go on and study enzyme kinetics. But, for a number of reasons, I was then looking for a part-time work. So when I got my PhD, so I was able to get a job in a department of pharmacology at Tufts Medical School. I didn't know anything about pharmacology at that time, really. Pharmacology has changed dramatically in the last 40 years. But I was sort of thrown into it. And I just liked it. I just liked the idea that a small molecule like Aspirin, can take your headache away. So I stuck with it. And rated my personal niche and I thoroughly enjoy it.

Chris Riback: Can I ask you a side question? You've said two things on the same, in the same vein that raised just a totally separate conversation or question for me, which is, twice you've said that you went through with something or went forward on something that you knew nothing about. Pharmacology, you just mentioned and then previously Taxol, you indicated you hadn't heard about it. For so many of us, that's an impossible task. So many of us feel, "Well, unless I'm an expert in something, I can't go forward with it." What made you go forward on two, you know, in so many areas that you didn't perhaps have the exact background on, according to you, but that didn't stand in your way?

Dr. Susan Horwitz: Well, that's the kind of person I am. I think that it's important to explore new things all the time. And when you have an interest in something, and I didn't have an interest in Taxol, because I didn't know anything about it, but I was curious. And, you know, it came at the right moment, when I had a new student looking for a thesis. But I do think it's important for scientists to explore new areas and especially to explore new ways of looking at the same problem. Too many scientists sort of do their PhD thesis over and over again. And you don't want to be that kind of a scientist. You want to be open to new technologies that are arising every day and you want to take your problem and use it in that technology. So I think that's important for a good scientist.

Chris Riback: So how does Taxol work? I realize its molecules bind to the microtubules in tumor cells, stabilizing them and ultimately, I believe, killing them. But describe, if you would for me, what is that process like in lay-person's terms. How does it work?

Dr. Susan Horwitz: Well just like we have a cytoskeleton, our bones, every cell in our body has a cytoskeleton. And a component of that cytoskeleton, a very important component, is the microtubule, because when a cell is going to divide, it's actually the microtubules that pull apart the DNA, that's in our nucleus, in our cells, so that each daughter cell, gets an equal amount of DNA.

So the microtubules have to perform exactly perfectly to get two normal cells. And if you take Taxol, which has a very specific binding site on the microtubule, those microtubules are like paralyzed and they cannot pull the DNA apart and you do not get two normal daughter cells. Daughter cells meaning the next generation of cells. And you have a serious problem. And eventually that cell will die. That is what Taxol does. When it binds to that site, it's a very specific site, and then the cell cannot divide properly.

Chris Riback: And Taxol of course, helps with multiple forms of cancer, ovarian cancer, breast cancer, lung cancer. Were you focused on any particular type of cancer? And you then discovered that Taxol worked across multiple forms? Or you were more looking at cures for, or ways to address cancer at large and these were the-

Dr. Susan Horwitz: I was looking for a way to treat cancer at large. I mean, when you start out with a new drug, you never know what's going to happen when you put it into a human. So that is the ultimate test, will a drug be useful in a patient that has a malignancy?

Chris Riback: And some of your current work, I understand, focuses on dormancy, the state when cancer cells don't divide. However, we shouldn't be fooled, even in dormancy. These cells are doing dangerous stuff, like producing inflammatory proteins, they can make the tumor cells migratory, which of course that's what is part of what leads to metastatic cancer. Describe for me, what's the work that you're doing there?

Dr. Susan Horwitz: Well, we doing two things, we have two projects in the lab, really, that I think are of interest, and which are being supported by the BCRF. One of them has to do with drug development. I mean, I've had a lot of experience with Taxol and I'd like to use that experience to try to develop better drugs and we need new drugs, particularly for triple negative breast cancer.

Chris Riback: Yes, why do we need new drugs?

Dr. Susan Horwitz: We need new drugs because, particularly triple negative breast cancer, there are no ways of treating this, except with chemotherapeutic agents and you know, cells become resistant to drugs. This is a very serious problem, one which I'm very interested in. And so we need new drugs to overcome some resistance. We need new drugs to make combinations of drugs and combinations of drugs with immunotherapy and it's targeted drugs. Many of which also use some of the agents such as Taxol, to deliver these together. So we do need new drugs, with new mechanisms and since I've had a lot of experience with Taxol, I'm looking for new drugs that might have similar activities with Taxol, but which would not show cross-resistance. And this is a project that I'm working on with Dr. Hayley McDaid. And also with Amos Smith, who is a colleague from the University of Pennsylvania, who is a synthetic chemist, because he's working with us and developing new molecules that may be useful for triple negative breast cancer.

We have some metastatic models in cell culture. We look at the ability of our cells to migrate through a Jello, a gelatinous matrix, to see if they have metastases. As I said, you really have to move on from cell culture, but it's a very good way of screening, looking for drugs that may be metastatic to inhibit metastases. So this is a whole area of drug development which I'm working and trying to use my knowledge that I've acquired over many years to help me in developing new agents.

Chris Riback: And, is that one area of work and then was there a second area that you were going to talk about or did that encompass both areas?

Dr. Susan Horwitz: No, I can certainly talk about the second area. It's something I'm very interested in.

Chris Riback: Yes, please.

Dr. Susan Horwitz: As I told you, Taxol binds, has a binding site on microtubules. Now, we know that microtubules are far more complex than we ever dreamt. And one of the things that makes them very complex, is that there are many different forms of microtubules. We call them isotypes. So there are many different tubular isotypes that make up the microtubule. So we know that a tumor, different tumors, have different isotypes in them. And the question that I'm so anxious to answer, is does Taxol or other molecules that interact with microtubules, doesn't have preference for some of the isotypes and then not interact with other isotypes? This has been a burning question for me and has been very difficult to answer. But now, we're able to clone and express the individual isotypes so that my goal is to have recombinant tubular isotypes in the laboratory so that we can study the interaction of Taxol with these different isotypes and this is very exciting. We're really making progress on this. And I'm able to do this because of the funding that I've received from the BCRF.

This is difficult research. It takes time, it takes tenacity. I work with Dr. Chia-Ping Yang on this problem who can look at a very challenging problem and not get discouraged and continue to work on it. And we're making progress.

So this would really be a wonderful thing. So not just me, but for many scientists who are interested in tubule and the interaction of drugs with different compounds.

So we have to look at tumors and we have to determine which isotypes are in that tumor. And then ask will Taxol interact well with those isotypes? These drugs, Taxol particularly, I'm sure anyone who's taken the drug can tell you this, has side-effects which are unpleasant. If you use a drug in an instance when you know it is not going to be successful, all the patient gets from this, is the side-effects. So we want to be more specific in who we give the drug to by understanding the different isotypes in the tumor.

So this is a big project. We are making progress, slowly but surely. And I hope to have these different recombinant tubular isotypes to study. Not just for me, but for, you know, the scientific community.

Chris Riback: Yes, you just hit on two points that I hear so frequently in these conversations. One is, the ability not to get discouraged, seems to be a genetic consistency among the top scientists. Because there is, there's so much room for, and I've had some of my guests describe it, it's not failure. They don't consider when experiments or research doesn't work the way they might have hypothesized, they don't even think of it, necessarily as failure, it's stepping stones and learning towards the next stage.

Dr. Susan Horwitz: That's right. But it can be discouraging.

Chris Riback: Well, Yes, I can imagine. But it seems that many of you lack that gene or it's a recessive gene maybe, at best.

Dr. Susan Horwitz: We try to keep it recessive and we try to keep it recessive for people with whom we work, because that's really very important to keep up everybody's spirits in the lab and really believe that progress can be made.

Chris Riback: And so, tying that in, you were discussing how important this research could be, for you of course, but also for other scientists. Translate that then for me down to the patient level. Is this where you are talking about the discovery of new treatments, of different types of treatments and by doing your work, you have the potential to almost feed a family or a big gathering of scientists who then can go and take some of your work and expand on it. Is that how you see it?

Dr. Susan Horwitz: Well I see it in different ways. For an example, we know that 50% of the patients, let's say with ovarian cancer who get Taxol, respond to it. And 50% do not. And we don't have any idea why 50% do and 50% don't. So one thought that I had was the possibility that the isotypes are different in these different patient populations and could that be partially responsible for why some patients don't respond to the drug? So we already have evidence that one of isotypes, doesn't interact well with Taxol. We've done that in the laboratory. And this could possibly give us, and this is not going to be we cure a 100% by any means, but it gives us an in of more understanding of how to treat patients. And, of course, the development of new drugs, with natural product origin, really can help patients who are resistant to the drugs that are available, or you hope that a new drug that you find, is going to be better than Taxol, with less side-effects. All of these things have to come together.

Chris Riback: Understood and when you say something like, you may not get, you certainly won't get or might not get to a 100%, one can still imagine if you're at 50% right now, what does a 10% improvement look like? You know, and when you're talking about 10% of a big number, even that's a lot of people. Or 20%, so any, I assume from your point of view, any improvement is improvement and unfortunately, because the denominator is such a big number, the improvement even by small percent, can mean impacting a large number of people.

Dr. Susan Horwitz: Yes, and a decrease in side-effects can really affect a lot of people. So these are the things that we're working on in the lab and trying to make progress with.

Chris Riback: So if that is a look forward, I'd like to close the conversation, and I don't usually close by taking a look backward or usually I try to, you know, close by looking forward, that's generally where these things go, but there's one more aspect about your personal story that just made me so curious and interested and I'd love to close there. We've been discussing, you were a pioneer and that's my word, not yours, in the use of natural products in fighting cancer. But by my math, you were a pioneer even before that.

Chris Riback: You graduated with a degree in biology in 1958 and then a PhD in biochemistry. I can't imagine that your field was overflowing with women at that time. What inspired you and what was it like to be a woman biologist then?

Dr. Susan Horwitz: You were right, it was not overflowing with women at that time and I can tell you many stories. When I actually went to Bryn Mawr with the idea that I would major in history, I didn't come from a family of scientists at all and when I arrived I had to take a science course. That was a requirement. And I thought, "Well I'll take it the first year and get it out of the way, and then I can study what I like." But actually, it turned out to be quite different. I took biology, I loved it. I changed my major and that's, I really enjoyed it tremendously. I majored in biology and minored in chemistry. And as I say, it's what I wanted to do and then I started looking for jobs actually, after my junior year thinking I would [fly] to Boston, my family was from Boston, I would come back and really there was nothing interesting at all.

I was offered a job at a company to take the dyes from the lipstick and put them in the eyes of rabbits to see if they were allergic to them. And that's certainly not what I wanted to do.

So I started looking into graduate schools. And, you know, some of the graduate schools that I talked to, I would talk to a professor and after that I'd say, "Thank you so much. Could you tell me where the ladies room is?" And they'd look at me and say, "The ladies room? There may be one down in the basement." This happened all the time. So the chemistry department just didn't think about women at that time. And then other places said to me, "Are you sure you want to get a degree in biochemistry? Or maybe you should get a degree in biology and then you could work at a museum."

So at that time, Brandeis University was starting its biochemistry department. It was brand new. I went there to look at the department, and I was delighted. There were two women on the faculty. This was the very beginning. I was in the first class. Mary Ellen Jones was an assistant professor. She was married, she had children. [inaudible] was also an assistant professor, married and had children. And I don't mean to say that you can't be a good scientist if you're not married or if you don't have children, but that's what I was looking for, and I was interested in my own personal life.

And so I was attracted to that. And so I went. And it was one of the best things I ever did.

Chris Riback: And I assume they had a women's room already built, since they had two faculty.

Dr. Susan Horwitz: That's right.

Chris Riback: Well, history's loss and the loss of one more historian was certainly science's gain. Thank you. Thank you for this conversation and obviously thank you for all the work that you have done.

Dr. Susan Horwitz: Thank you very much. Pleasure to talk to you.

Chris Riback: That was my conversation with Dr. Horwitz. My thanks for Dr. Horwitz for joining in and you for listening. To learn more about breast cancer research, or to subscribe to our podcast, go to bcrf.org/podcasts.

Breast Cancer Survivor Sonia Kashuk To Be Honored with Unsung Hero Award

 

Jenny B. Fine, Sonia Kashuk

Sonia Kashuk was in a London hotel room when her phone buzzed. It was a text message from Jenny Fine at WWD. As a maven of the makeup industry, Sonia had developed a professional relationship with Jenny over the years. But this message wasn’t about business.

“Jenny asked if I had time to talk,” remembers Sonia. “I said, “Absolutely, call me.”

Jenny’s doctor had felt a suspicious lump on her breast and was recommending additional screening. While nothing had been confirmed, Jenny immediately thought of Sonia. Just a month earlier, Jenny was struck by a speech Sonia gave recounting her own experience as a breast cancer survivor. Whatever the next step was, Jenny felt Sonia was the right person to help lead her through it.

“I needed a spirit guide,” Jenny said. “I decided Sonia was going to be that person. My gut told me she wouldn’t hesitate to assume that role – and she didn’t.”

Soon after, Jenny was diagnosed with triple positive breast cancer. Next came chemotherapy, surgery and then radiation. Sonia, who had been down this road a decade earlier, became a crucial member of Jenny’s support team.

“I tried my best to be there for her every step of the way,” Sonia said.

And she was. At the upcoming New York Hot Pink Party on May 15, Jenny will present Sonia with The Roslyn and Leslie Goldstein Unsung Hero Award to recognize Sonia’s unflagging support during her challenging course of cancer treatment.

Sonia modeled her caregiving approach after her mother, who was a 25-year breast cancer survivor when Sonia was diagnosed in 2006. Sonia’s mother not only supported her during treatment, but she also gave her hope for a future beyond her disease. 

“I had such a great role model in my mother. I wanted to be that person for Jenny,” Sonia said.

Throughout Jenny’s treatment, no topic was off limits. Over phone calls, lunch dates and text messages, they discussed everything from clothing suggestions for Jenny’s double mastectomy recovery (“tops with buttons on the front”) to explaining what surgical drains were. 

“Nothing was off the table. Sonia shared all of the nitty gritty,” said Jenny.

As mothers to young daughters, the women also shared how to handle the diagnosis with their families.

“How do you deal with it at school? Do you tell the other moms?” said Jenny, recalling the questions she asked Sonia.

Most importantly, “What’s the ongoing conversation you have with your daughter about breast cancer?”

Sonia was well-suited to answer that question.

For Sonia, developing breast cancer was not a matter of an “if” but a “when.” Her grandmother passed away from breast cancer, and her mother is a breast cancer survivor. To mitigate her risk, Sonia received regular screenings, waiting for the moment when disease would strike. When an MRI detected early stage breast cancer, Sonia opted for a double mastectomy.

As Sonia looks to her daughter, Sadye, she relies on research to unlock clues to help families like hers manage their breast cancer risk.

“Everyone impacted by breast cancer is in search of answers for themselves or a loved one,” Sonia said. “Research discoveries pave the path forward.”

Jenny feels the same way.

“Breast cancer research saved my life,” Jenny said. “Not only does it aim to eradicate this disease, it has far-reaching implications for other kinds of cancer too.” 

Jenny has been a fervent supporter of research, yet her breast cancer diagnosis has remained relatively private. One hint of her experience lies in her current hairstyle – something that Sonia endorsed after Jenny went wigless for the first time.

“She said, ‘You have to keep it,’” Jenny said recalling the moment. “Just when I was feeling self-conscious, Sonia gave me that boost.”

Jenny hopes by sharing her story publicly, she will inspire other young mothers to monitor their breast health and support research.

“Despite everything, there have been some silver linings to this breast cancer experience,” Jenny said. “Being able to share with others the profound impact Sonia had on my life is one of them.”

PRESS RELEASE: Breast Cancer Research Foundation Announces New Chief Scientific Officer, Dorraya El-Ashry, to Lead Research Mission

 

Dorraya El-Ashry

May 6, 2019, New York, NY—Today, the Breast Cancer Research Foundation (BCRF) announced that breast cancer researcher Dorraya El-Ashry, PhD, joined its executive leadership team as Chief Scientific Officer. Dr. El-Ashry will work with the Foundation’s Scientific Advisory Board (SAB) to set the science vision each year, selecting the world’s best investigators to work on the most promising and urgent research needs, and managing all scientific aspects of the BCRF portfolio of grants.

As Chief Scientific Officer, El-Ashry will directly influence the course of breast cancer research around the world, leading BCRF’s multi-million-dollar grant program and serving as a breast cancer expert and spokesperson. In 2018-19, BCRF invested $63 million in breast cancer research, supporting 300 researchers at leading academic and medical institutions across 14 countries.

“We welcome Dr. El-Ashry to the leadership of BCRF’s large, vibrant and highly productive research endeavor,” said Dr. Larry Norton, BCRF Co-Scientific Director. “Furthering the work of 300 dedicated investigators around the world is an enormous challenge. Dr. El-Ashry’s personal involvement in cutting-edge breast cancer research for over two decades as well as her extensive knowledge of science and scientists give her a special perspective on the task. We look forward to her successful stewardship of our great mission.”

El-Ashry’s entire career has been in breast cancer research—initially compelled to study the disease in college after witnessing two of her best friends cope with their mothers being treated for or lost to metastatic breast cancer. Two of her aunts, one of them being just 39 years old with two young daughters, her grandmother, and several friends and colleagues have either been treated for breast cancer or died from breast cancer.  Her personal experience fortified her determination to eradicate the disease through research.

El-Ashry’s research focus was on mechanisms of estrogen receptor (ER)-negative breast cancer. Her lab identified factors that drive the reversible loss of ER, such that inhibitors of these factors could restore both ER expression and responses to anti-estrogen therapies. Her lab also identified a microRNA signature that could predict poor outcome and resistance to anti-estrogen therapies.

More recently, her focus turned to those cells that surround, support, and drive many of the aggressive behaviors of the cancer cells, and in particular, a cell type known as cancer associated fibroblasts (CAFs). She and her colleagues discovered that these CAFs move along with circulating tumor cells (CTCs) in patient blood and play important roles in breast cancer metastasis.   

El-Ashry was most recently Associate Professor of Laboratory Medicine and Pathology at the University of Minnesota/Masonic Cancer Center, and prior to that, Associate Professor of Medicine at the University of Miami/Sylvester Comprehensive Cancer Center, Assistant Professor of Internal Medicine at the University of Michigan, and Assistant Professor of Oncology at Georgetown University/Lombardi Cancer Center.

She graduated from Vanderbilt University and then went on to receive her PhD in Experimental Pathology from the University of Colorado Health Sciences Center, performing her post-doctoral training at the Lombardi Cancer Center.

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How Video Game Technology May Help Cancer Researchers Improve Treatment Outcomes

 

At the 2019 AACR Annual Meeting, BCRF researcher Dr. Peter Kuhn and his fellow collaborator Dr. Jorge Nieva shared how they are collaborating to improve patient care using an unorthodox method: video game technology reimagined by the physicist and validated by the physician.

The genesis of this project stemmed from a common challenge in patient care: helping clinicians make informed decisions for their patients using unbiased data. This difficulty is commonly found when doctors try to asses a patient’s performance status – that is, their ability to perform daily activities.

A common approach doctors undertake is by observing a patient moving from a chair to the exam table. However, reading the results of this exercise are prone to bias and are not always straightforward. 

To resolve this, Dr. Kuhn, a trained physicist, rewired a Microsoft® Xbox Kinect motion sensing device (similar to the motion detecting technology popularized with the Nintendo Wii) to get an unbiased measurement of movement and patient performance status. 

“Digitizing cancer and digitizing health can in fact really help us to deconvolute health care disparities,” Dr. Kuhn said.

Indeed, not only could this approach lead to an objective measurement, but it has the potential to be used as a biomarker to predict poor outcomes.

While this sounds promising, the device must be proven in a clinical trial setting in order for physicians like Dr. Nieva to adopt it. 

“Whenever a physicist shows me a cool technology, the first thing I want to do is to prove it in a clinical trial that it actually works,” Dr. Nieva said.

The pair are ready to embark on the next step of their work together. While it remains in its preliminary stages, they plan to use the devices to analyze patients’ performance status between doctors’ visits. Since the devices are small and easy to transport, patients will be able to use them at home regardless of where they live. The hope is this technology may increase patient participate in clinical trials and improve treatment outcomes.  

Investigating Breast Cancer: Dr. Gabriel Hortobagyi

 

BCRF podcast art

Subscribe to the podcast here:

At first glance, it would seem that any of us who follow the breast cancer experience would look to the investigators – the scientists, researchers and their teams – for inspiration. They are, after all, dedicating their lives to fighting cancer.

In this conversation, you’ll hear the opposite. To listen to Dr. Gabriel Hortobagyi, you hear the inspiration and insight that he and his teams gain from the grace of breast cancer patients – in particular, people who have triple negative breast cancer and their families.

You’ll also hear about the unique, novel research that Dr. Hortobagyi and his colleagues are doing to investigate resistance to various therapies and ways to develop combination therapy to overcome the resistance. This was a powerful, thoughtful, hopeful conversation with a scientist who knows, as he says, that the patient is the most important player on the team.

Dr. Hortobagyi is a Professor in the Department of Breast Medical Oncology at the University of Texas MD Anderson Cancer Center. He is also the Chair of the BCRF Scientific Advisory Board.


Read the transcript of the conversation below:

Chris Riback: I’m Chris Riback. This is Investigating Breast Cancer, the podcast of the Breast Cancer Research Foundation and conversations with the world’s leading scientists studying breast cancer prevention, diagnosis, treatment, survivorship and metastasis.

At first glance, it would seem that any of us who follow the breast cancer experience would look to the investigators – the scientists, researchers and their teams – for inspiration. They are, after all, dedicating their lives to fighting cancer.

In this conversation, you’ll hear the opposite. To listen to Dr. Gabriel Hortobagyi, you hear the inspiration and insight that he and his teams gain from the grace of breast cancer patients – in particular, people who have triple negative breast cancer and their families.

You’ll also hear about the unique, novel research that Dr. Hortobagyi and his colleagues are doing to investigate resistance to various therapies and ways to develop combination therapy to overcome the resistance. This was a powerful, thoughtful, hopeful conversation with a scientist who knows, as he says, that the patient is the most important player on the team.

More about Dr. Hortobagyi – he is a Professor in the Department of Breast Medical Oncology at the University of Texas MD Anderson Cancer Center. He is also, not insignificantly, the Chair of the BCRF Scientific Advisory Board.

Among his many honors and positions: He has served as Past President of the American Society of Clinical Oncology, as a member of the U.S. National Committee for the International Union Against Cancer, on the National Cancer Institute’s Breast Cancer Progress Review Group, chaired the Steering Committee of the Breast Health Global Initiative, and well, the list could go on.

Dr. Hortobagyi, thank you for joining me, I appreciate your time.

Dr. Hortobagyi:  Thank you for having me in this program.

Chris Riback: Again, congratulations. You are now about six or eight months into your run as chair of BCRF's Scientific Advisory Board. Is that what you thought it would be?

Dr. Hortobagyi: Well, I have been involved with this organization since inception, so I've seen from inside the evolution of the SAB, and it's clearly an honor to take the next step and be in charge for a while.

Chris Riback: What's your mission for the board? I'm not sure how long your term is for, but what are your goals? How might you hope that your time is remembered?

Dr. Hortobagyi:  BCRF is a somewhat different organization, and it is run less formally than many other granting agencies, and by that I mean that while most other agencies just publicize a granting mechanism and let investigators stake the initiative for supplying and proposing projects. We invite people who have already demonstrated success in breast cancer research and on the basis of their track record, we ask them to apply, that is quite different. It's a totally unique model in America or around the world for that matter. The scientific advisory board evolved from a small nucleus of people, who were involved with Claire, Norton, and Evelyn Lauder in the development of this organization.

And therefore, the activities of the scientific advisory board are less formal, than other organizations where people might to go through an entirely different process to join. Having said that all members of the scientific advisory board are fairly senior, and fairly well-known on the basis of their scientific contributions to the field. So the state's original objective of the Breast Cancer Research Foundation and therefore of the scientific advisory report, is to eliminate the suffering caused by the diagnosis and development of breast cancer, in the universal population. And in order to accomplish that, our purpose in the scientific advisory board is to recruit the top investigators not only within the United States, and elsewhere in North America, but the rest of the world.

Because cancer doesn't have borders and of course, science does not have borders. So our function is to identify those people who should be supported by BCRF. And with that support move the needle towards prevention and cure of breast cancer. And when cure is not possible, then amelioration of quality of life and a better control of symptoms, whether physical or psychological or otherwise.

Chris Riback: What an incredible opportunity and responsibility obviously, but it feels from your description that it allows somebody like you to go beyond the work that you're already doing. I mean you've already obviously dedicated your life to the mission that you just described. Helping reduce or eradicate the suffering that occurs from breast cancer. And it's almost a way to go beyond yourself and identify the other researchers, scientists who are doing extraordinary work, maybe work in other forms of cancer, and find ways beyond your own research to help fight the disease and help address the problem. At least that's how I'm interpreting part of what you're saying. I don't know if that's how you view it.

Dr. Hortobagyi:  Absolutely, so all of the senior members of the Scientific Advisory Board have had decades of experience, and dedication to this particular project and to breast cancer research at large. So throughout those decades, all of us have come in contact with the great majority, if not all of the most recognizable and most accomplished investigators in the field. And we view our function as not only identifying those that we know about, but also those who are emerging and who are the next generation of investigators. Because eventually we will have to pass the baton on to the next group of people who will continue after we are history. And that of course means continuously interacting with other investigators in the field, and identifying people through our own collaborations, through attendance of meetings, through reading journals, through round tables discussions, conferences, congresses and whatnot.

And in the process, we also try to balance the BCRF portfolio. By that I mean that there's no organization that has infinite resources. So we need to manage the resources that BCRF is able to raise in the most efficient way. And if we have let's say 200 funded investigators, we do not want to spend the resources on 175 of them doing the same thing. So we try to balance the portfolio so that there is substantial attention being paid to all of the emerging opportunities, for prevention, early diagnosis, monitoring, surgical and radiation therapy, systemic treatments, targeted therapies, and of course the management of survivorship, which in itself is an emerging field of science.

So all of that requires continued discussion and of course we are unable to fund all the people we would like to fund, or all the projects we would like to fund. But we do our very best to balance the portfolio so that we have a prominent investigators, and leading projects in all areas that we consider important to improve our ability to treat, and manage and cure breast cancer.

Chris Riback: Yes. Well it certainly is an extraordinarily balanced portfolio and the range of projects, and power of projects is really something. I also appreciate the analogy that you mentioned earlier, in that last response about party responsibility at some point will be to pass the baton. Unfortunately for you, fortunately for you I should say that that time is not yet, so let's talk about you and let's talk about your research, and the work that you do. In reading about you, I came across a very intriguing statement that you made a couple of years ago. You said breast cancer is the prototype for cancer prevention. What did you mean by that?

Dr. Hortobagyi: What I meant by that is the observations that we have made in the course of managing breast cancer over the past 40, 50 years, have led to new directions in treatment that not only satisfied the need for improving treatment, curative treatment of primary breast cancer, but also opened doors to preventing additional breast cancers. So let me expand a little bit on that.

Chris Riback: Yes.

Dr. Hortobagyi: Once you have one breast cancer, you have a certain finite risk of developing another breast cancer, a second or in sometimes a third breast cancer. And that varies depending on certain risk factors, so for instance if you have totally average risk, you're an American born and raised a woman, then you would have about a one in 10 chance of developing breast cancer, if you survive and are cured from your first breast answer, when that second breast cancer will occur. And where in the remaining breast, if you had breast conserving surgery or the contralateral breast if you did not, is not quite predictable, but the risk is estimable, now if you have a strong family history of breast cancer. You are a carrier of one of the gene mutations, or you have such a strong family history that you have multiple siblings, first cousins, first degree relatives in general.

 Then you risk is substantially higher. And we have observed during the development of what we call adjuvant systemic therapy, but especially adjuvant hormonal treatment or endocrine treatment, that when you administer a drug such as Tamoxifen, or such as Anastrozole, to patients with hormone receptor positive primary breast cancer, not only do you decrease the risk of a reoccurrence of that breast cancer or metastasis from that breast cancer by about 50%, but you also reduce the risk of developing a second or contralateral breast cancer by about the same proportion.

So it was that first observation, which was actually made in the 1980s that we stopped and thought, "Gee, this sounds very much like a prevention intervention." And on the basis of that we developed an entire program. We ... I'm using the royal we, but I'm talking about the breast cancer community, and that led to six or seven very large prospective randomized trials that the in fact demonstrated, that if you take individuals at risk for developing in this case not the second, but the first breast cancer, based on a variety of risk factors, then you can reduce that occurrence by about 50%.

It's a little bit lower than 50%, let's say 4 or 5% or so. If you use either five years of Tamoxifen, or a similar duration of drugs such as Anastrozole or Letrozole or Exemestane, which are the aromatase inhibitors we use to treat advanced breast cancer, but in this case they would be used as a primary prevention for breast cancer. And so that has been amply documented, and because of that, because this was actually the first observation, but was not only determined that anecdotally, but confirmed prospectively in multiple trials, and the large meta analysis that was performed after all the trials were completed, that we made the statement, that breast cancer is the prototype for a cancer prevention.

And that similar observations can be made certainly in other hormone dependent cancers, and perhaps under different circumstances using different interventions in other malignancies of man and woman.

Chris Riback: It's been one of the consistent themes of this conversations, and part of the discovery that's been really amazing for me in particular, it is just what you described, the way that lessons, insights, successes, failures in one area of cancer get translated if you will, into other areas. And so many of the scientists that I've gotten to talk with have taken findings or insights from prostate cancer, or some other area and apply it to breast cancer and in reverse as well, which I take as a little bit of what you're saying. Maybe not everything that you're saying, but a little bit of what you're saying. An area of your research, triple negative breast cancer. That is a tough area to work in obviously, probably you'll tell me if you disagree, it might not get tougher than that. Why do you focus there?

Dr. Hortobagyi:  If you ... Forgive me, I would like to step back one second just to make a comment about what you just said, prior to asking me this question about triple negative breast cancer, because I think it is an enormously important observation you made.

Chris Riback: Yes please.

Dr. Hortobagyi:  And that is the major reason why the overwhelming majority of scientists support research for the sake of research, as opposed to purely applied research. Let me explain. When you work for the pharmaceutical industry and you're a scientist, your task is to develop eventually a commercially viable product that your company can sell, while at the same time of course doing some good by serving as treatment for a condition of one sort or another. In pure science you ask fundamental questions without necessarily knowing where you're heading with that. And this sometimes frustrates lay folks and politicians at large, who have to divvy up limited resources. But the fundamental research supported for instance by the National Institutes of Health, or in the case of this conversation by BCRF, is incredibly important. Because the reality is that most applied research fails at the moment, not necessarily forever, but it fails when you do not have answers to other related questions.

And it is because of the uncertainty of where the next step forward is going to come from. That it is so important that we support all research related to in this case cancer, because it is not only what applies to breast cancer that will work for breast cancer, but the next observation as you mentioned in prostate cancer or perhaps in melanoma, or perhaps in leukemia and sometimes in I don't know, multiple sclerosis or cardiovascular disease, will be the piece of the puzzle that is missing in order to take the next giant step forward in controlling, curing or preventing breast cancer. That is a concept that is so important and so fundamental in the field of research, that we can not for a second for get it. All right now let me get back to your question about triple negative breast cancer.

Chris Riback: Of course, but thank you obviously for making that point and putting a punctuation mark on it, because yes it certainly seems that way. And it really has come across from these conversations and in particular, and this is maybe something for a separate conversation at a time when so many science budgets are maybe getting cut in various areas. Yes the point that you just made is just so incredibly important so thank you for that. And so to talk to me ... Triple negative breast cancer, devastating obviously.

Dr. Hortobagyi: So triple negative breast cancer is defined as a lack of expression of three gene products, estrogen receptor, progesterone receptor and the human epidermal growth factor receptor 2, HER2 and therefore being negatively defined as opposed to being defined by a positive attribute. It is a wastebasket diagnosis as we call informally, because it is not a single condition, but it is a group of diseases that just happen to share those characteristics. The lack of expression of ERPR and HER2, that group represents about 15% of primary breast cancers. Somewhat higher proportion of metastatic breast cancers, because it prognosis of primary triple negative breast cancer is less favorable than that of the rest of breast cancer.

Therefore, it is disproportionately over represented in the metastatic setting, stage by stage it is associated with a less favorable prognosis after optimal therapy. Then either the luminal types of breast cancer or the HER2 enriched breast cancers. And to a large extent that is related to the fact that we do not have a single effective targeted therapy to use, as opposed to the luminal cancers where we have multiple targeted therapies, including all the endocrine agent and CDK 4/6 inhibitors and [inaudible] and the tire seen kinase inhibitors etcetera, and in the HER2 enriched population where anti HER2 therapies such as monoclonal antibodies and tire seen kinase inhibitors and antibody drug conjugates have made an enormous difference.

So if we go back about 20 years when HER2 was first identified, and the diagnostic was discovered that time ... And if you were able to classify your breast cancers into hormone receptor positive, and hormone receptor negative, and the third group as being HER2 enriched, well the worst prognostic group was HER2+ or HER2 enriched group. The second worst prognostic group was the cripple negative group, and the best prognostic group was the hormonal sensitive, or the hormone receptor positive group. Since the development of all these targeted therapies for HER2+ disease, that has become arguably the most favorable group, because treatment make such an enormous difference, that this poorly prognostic group has become a favorable prognostic group.

Something similar has happened, although it's less dramatically in the hormone receptor positive groups, and the orphan in this remain the triple negative group of breast cancers. Now to the best of our understanding triple negative breast cancer is a conglomerate of probably five or six or maybe seven molecularly distinct subgroups. And because they are different, the likely emergence of an effective targeted therapy will be different for each of the subgroups. And that's what has complicated the matter here. So some of those triple negative subgroups are apparently androgen receptor positive.

Others express a molecular profile that suggests that they are manipulated by immunological reactions, and therefore might be candidates for modern immunotherapy, some others are very basal like tumors that lack just about all of the other characteristics from the other groups, but they may have mutations or over express genes that accelerate their growth and division, and the dissemination throughout the body. And those might require yet a different group of targeted therapies. So my team has focused on this triple negative breast cancer, and continues to focus on that, both in the lab and clinical trials, in the lab we have worked in the development of PARP inhibitors and more recently in the development of checkpoint inhibitors, immunological checkpoint inhibitors, PD-1 and PD-L1 inhibitors.

And in the combination of these two groups of agents, so PARP inhibitors with PD-L1 inhibitors and PD-1 inhibitors, in the clinical arena we have developed what we call a bucket clinical trial schema in which we take all patients with triple negative breast cancer, and sequence their genome, well not their entire genome, but let's say several hundred of the genes that are commonly associated with the development of breast cancer in general, in triple negative breast cancer in particular. And through that sequencing, we identify those molecular abnormalities that could serve as therapeutic targets, and we focus especially on those therapeutic targets against which there are either approved, or investigational drugs in development.

Because when you do that, you divide a really small population into even smaller subgroups, we can't possibly hope for running large randomized trials in each of those subgroups. So instead ones we identify a molecular abnormality. If we have a targeted treatment that might be useful to test against that molecular abnormality, then we place that patient and that treatment into one bucket and treat them, and we hope to accumulate enough numbers in each of those buckets of which there are a pretty good number by now. So at the end of the day we can come up with some practical conclusions of, this drug is likely to work in this particular setting, in the face of this particular molecular abnormality, or this combination of drugs might do that.

So that has been the focus of the MD Anderson Moon Shots Program, which is focused entirely on triple negative breast cancer. In the meantime as I mentioned earlier, we are working on specific areas of interest, immuno-oncology and the contribution of PARP inhibitors and checkpoint inhibitors should be controlled, and eradication of triple negative breast cancers.

Chris Riback: How do you or how would you explain to me the Moon Shot Project obviously ... It's a Moon Shot project and by its nature ... And it kind of relates perhaps a bit to what you said earlier, that so much of researches needs to be done for research sake and it may or may not deliver immediately, but you learn different things, and it may deliver in other areas. And at the same time just maybe a moon shot lands. What do you communicate or how do you communicate where you're at, to people who suffer from triple negative breast cancer or family members, I guess in terms of your hypothesis. And then I know you're just gathering data, so it's likely too early to start discussing what you might be seeing.

But anything that you can say about your hypothesis and the testing of your hypothesis, vis a vis the trials that you're doing?

Dr. Hortobagyi: Well so clearly this is teamwork. And when I say teamwork, it's not only a team of scientists and clinicians, but it's a team composed of patients, their families, funding agencies, pharmaceutical companies and all of the scientists and physicians involved in this. So we considered that we are the patients partners in this enterprise, because the patient is the single most interested party in this team, and we are their agents so once you understand that position in the team, then you realize that you have to be very transparent about what you do. So whenever we see a patient with triple negative breast cancer for the first time, we spend a fair amount of time, we meaning the physicians and also our clinical team, the nurses, nurse practitioners, clinical pharmacists, etcetera, to make sure that we impart as detailed in education about what triple negative breast cancer is all about.

The limitations of our current treatments, what is realistically achievable with the state of the art acknowledgement today, and what we're hoping to get to in the process of developing novel treatments. And in that process then we explain why we need to do certain things. So for instance we tell them about what we understand about the molecular biology of triple negative breast cancer, what we already know are the major molecular abnormalities, the p53 mutations, the EGFR over expression, the Pf3 kinase mutations, certain pathways that are disregulated and so on. Without trying to drown the main in scientific gobbledygook but, so as to tell them that we already have made a certain amount of progress in understanding in greater detail, in greater depth what we think makes a triple negative breast cancer or such an aggressive disease.

And then we take the next step by saying, "But we hope that in the process of attacking those molecular abnormalities we already know about, we can take steps to understand what else treatment accomplishes. And for that we need to do a second biopsy so that after we start your treatment with let's say an anti EGFR antibody that we know what happens to two weeks or two months later. And we can correlate that to the clinical response as well as to the molecular changes that take place. And only by doing this systematically will we learn why certain treatments based on a solid scientific hypotheses work, and why are other treatments based on equally solid scientific hypotheses do not work, and we will understand mechanisms of resistance, we will understand why certain molecular abnormalities are passenger abnormalities, and not drivers off of the behavior of triple negative breast cancer."

So in that sense, then we developed this partnership with patients and I can tell you that our experience has been that patients are rather excited about being part of this team. And, and they are very willing to push forward with not only our recommendations, but they're making suggestions about why didn't you do this too? So that we can contribute to knowledge in addition to benefiting from the evolving treatment that you are developing. So it's been quite exciting to see this because I remember recently I said 10, 12 years ago when the conversations in our major oncology meetings were along the lines of physicians discussing among themselves that, “Oh, patients would never go for having to biopsy them again, because biopsies are such a horrible things to do.”

And it turns out that when you ask patients and you explain to them why you want to do a first, and then the second biopsy, and they understand what you are trying to accomplish, they are much more aggressive than most physicians would be. So it's been an interesting evolution. Now over the past 10 years I would say that a distinct majority of oncologists both in community practice, and in the research community have come around and are much more accepting of what we need to do, in order to understand what our treatments do and how cancers evolve throughout treatment.

Chris Riback: Well, it's so interesting to hear about, and it's got to be very inspiring for somebody like you and for the other researchers, and all the medical practitioners. I mean you describe these patients as the primary player, and surely they are part of a club, part of a team that they never wanted to be on. But I would imagine that what I'm hearing from you is they see a ... Not all of them but the ones that you're talking about and the ones who are able, see a cause that is perhaps bigger than themselves, and the opportunity to almost literally give something of themselves for other people, and for the research. And that's gotta be incredibly humbling and inspiring for somebody like you.

Dr. Hortobagyi: One of the interesting things that I've learned throughout my career, and I must just mention here that I learn something from every patient I see. It is truly an amazing process, one of the things I learned, and it took me years and years to understand it, is that I always thought that cancer was and is a horrible disease. It can be disfiguring, it can cause an incredible amount of suffering and symptoms and pain and of course expenses and it leads people into bankruptcy. And many still die of it. So I always thought of it as this horrible, absolutely horrible thing that had incomprehensible raise on debt. And yet I saw time and time again and heard from many of my patients that cancer has made them better people, and it was hard for me to understand that, I tried to put myself in their shoes and I would imagine that if I develop breast cancer, I would be angry.

I would be frustrated, I would be really crying out for why me and how could this happen to me, and just lash out at everything and everybody around me. And very few of my patients do that if any, because being faced ... And this I'm just synthesizing to you many years of trying to understand this, I tried to face a potentially lethal diagnosis. It refocuses their mind the and so many of the peripheral and superficial things that we worry about as human beings in our usual [inaudible] life, just fall by the wayside. And they stop being important and they start focusing what they eventually define as the most important things in their life. And those become to a large extent relationships.

So family, friends, children, grand children, and so many of the other annoyances just stop being important, and they just sort of disappear. And by making that transition, that transformation into focusing on what is really important in life, they become better people. And in that sense they are better people than those of us who treat them because we still carry that baggage of focusing on minor things, and minor irritants in life. And this has been an incredible phenomenon, and understanding that is totally humbling.

Chris Riback: That is such an extraordinary insight and I can only imagine to see, to experience that level of grace and see it in action, and perhaps regularly as you do. Yes, that really must change one's view and open some eyes. Thank you. Thank you so much for the conversation. Thank you for the work that you do and your team does every day.

Dr. Hortobagyi: It's an honor and a pleasure to be involved in something that is more like a hobby for me. In retrospect I would have done it even if I didn't get paid for the work I do, and it has been incredibly rewarding.

Chris Riback: That's terrific. We'll make sure that the powers at the Anderson Cancer Center don't know that you would actually work for free. We'll try to make sure ... But your point is understood. Thank you. Thank you for your time.

Dr. Hortobagyi: My pleasure.

Chris Riback: That was my conversation with Dr. Hortobagyi. My thanks to Dr. Hortobagyi for joining and you for listening. To learn more about breast cancer research or to subscribe to our podcast go to bcrf.org/podcasts.

 

BCRF Featured in Amazon Mother’s Day Gift Guide

 

Spring is in the air – and so is Mother’s Day. Ahead of the holiday that celebrates the incredible women in our lives, our friends at Amazon have created an easy way to find the perfect gift for mom while supporting lifesaving research.

BCRF is one of the hallmark partners for Amazon’s first-ever Mother’s Day gift guide with all products supporting worthy causes. The guide features over ten BCRF corporate partner brands and dozens of products that give back to BCRF. From household items to jewelry, fitness apparel and accessories, you’ll find fabulous gifts that give twice for every woman in your life.

Check out the full gift guide here and see the list of BCRF-supporting brands below:

  • Apollo Tools
  • Alex Woo
  • Conair
  • Cuisinart
  • Everlast
  • Glyder
  • Lokai
  • Spring Meadow
  • Streamlight
  • S’well
  • Rabbit Air
  • Vivora

10-Year-Old Wants Kids Everywhere to Take the Pink Lemonade Stand Challenge This Summer For Breast Cancer Research

 

Pink Lemonade Stand Challenge

For the fourth summer in a row, 10-year-old Brynne Rhodes will break out her pitcher and pink lemonade to raise funds for BCRF – and this year, she’s challenging kids in every state across the country to do the same.

Brynne, who is now a veteran fundraiser, donated $100 to BCRF in 2016. Last year, kids from Maine to Alaska were inspired to join her. Together they organized more than 50 stands across 15 states and several were featured on local media. Collectively, they donated more than $10,000 for lifesaving research.  

For Brynne, the cause is personal. She started her pink lemonade stand after her mom, Kim, was diagnosed with breast cancer in 2015. Unfortunately, this was not the first time her family was impacted by the disease. Brynne’s great-grandmother, grandmother and aunt had all previously been diagnosed with breast cancer and she fundraises to honor their memory. 

Kim is grateful for the treatments and research that saved her life.

“This is our way of paying it forward," she says. "We need to stop breast cancer before the next generation has to face this terrifying illness." 

Inspired by their connection to the cause, Brynne and Kim are encouraging others to take on the Pink Lemonade Stand Challenge. The mother-daughter team recently appeared on the Today Show asking for the nation to help them reach their goal of having pink lemonade stands in each of the 50 states.

 “We’re excited to get more kids involved this year and help make a difference,” Brynne says.

Interested in taking on Brynne’s Pink Lemonade Stand Challenge? 

Here’s how you can get involved:  

1) Regardless of where you live, organize your own pink lemonade stand this summer and pledge to donate the money you raise to BCRF. 

2) Count the money with the kids and make a donation to BCRF using this link. You can use your credit card to make a donation in an amount equal to the amount raised at the pink lemonade stand.

3) Stand with us - together, we will be the end of breast cancer!

Interested in creating your own fundraising page for your pink lemonade stand? Go to https://give.bcrf.org/PinkLemonadeStandChallenge and click the orange “Join Team” button on the left hand side!

What is a Liquid Biopsy?

 

A liquid biopsy is commonly used in clinical and laboratory research to identify and measure biomarkers. Several sessions at the 2019 AACR Annual Meeting in Atlanta were dedicated to this topic. These blood-based tests give researchers the ability to look at the unique characteristics of a cancer cell, without performing an invasive procedure.

What is a biomarker?

To understand the promise of liquid biopsy, we must first understand biomarkers and how they are used.

A biomarker can be thought of as a molecular flag that helps doctors decide on a course of action for each patient. A biomarker can be a gene, protein, or other measurable marker and should consistently mean the same thing.

For instance, a mutation in the BRCA1 gene is a biomarker for a high risk of breast, ovarian and other cancers. When detected before cancer, surgical removal of the breast and/or ovaries can prevent a future breast or ovarian cancer. When detected after a cancer diagnosis, a germline (inherited from a parent) or somatic (occurring only in the tumor cells) provides clues to what kinds of treatment is most likely to kill the tumor cells.

Advances in liquid biology technology and the remarkable pace of discovery of potential new biomarkers makes liquid biopsies a valuable research tool. Liquid biopsies allow clinical researchers to get non-invasive serial samples of blood, urine or other bodily fluid as the patient progresses through treatment. The goal is to move liquid biopsy from the research arena into the clinical arena where it can improve the care of patients and we’re making progress in that direction.

Circulating tumor cells (CTCs) are another example of a biomarker that can be measured in the blood of cancer patients. The presence of CTCs has been shown to predict recurrence after treatment of early-stage breast cancer. Changes in the number of CTCs during treatment can indicate that a tumor is not responding to treatment or has spread to other tissues.

Coupled to single-cell analysis where changes in tumor markers can be measured in individual tumor cells, liquid biopsies are helping researchers to understand the process of tumor evolution – progression from a primary cancer to metastasis – and help identify new targets for prevention or treatment of metastasis.

The promise of liquid biopsy

As the underlying technology of liquid biopsy continues to evolve, researchers are discovering circulating factors beyond genes and proteins that can provide clues to tumor response, progression and cancer risk.

Liquid biopsies hold tremendous promise for patient care: they can reduce the need for tissue biopsies – an invasive and sometimes painful procedure – as well as the number of imaging appointments to determine the tumor’s response to therapy, or to augment screening mammography.

The hope is that liquid biopsies will routinely be used for these purposes, but also to detect early-stage breast cancer or identify biomarkers of risk before cancer occurs. This continues to be a major focus in the liquid biopsy field.

One of the prevailing challenges is that rapid pace of biomarker discovery with liquid biopsy is outpacing our capacity to verify that the biomarkers that are found are clinically meaningful.  This takes carefully designed clinical trials and patient volunteers.

As with many discoveries that have improved breast cancer, BCRF has supported the development and application of liquid biopsy by funding innovators who have moved the field forward, such as Daniel Haber, James Hicks, Michael Wigler and many others who are now applying the technology to their research studies to accelerate biomarker discovery.

Breast Cancer Treatments: Current, New and Emerging Therapies

 

Breast cancer deaths have declined dramatically in recent decades and are nearly 40 percent below their peak in the late 1980s. While this trend may be partially attributed to improvements in screening and early detection, treatment advances play an even larger role.

At the 2019 AACR Annual Meeting, BCRF investigator and outgoing president of AACR Dr. Elizabeth Jaffee chaired a session where breast cancer experts discussed the landscape of treatments for breast cancer subtypes and emerging therapies in clinical trials or in development.  

Estrogen receptor-positive (ER) breast cancer. ER-positive breast cancers are the most common and the most treatable form of breast cancer. ER-targeting therapies have played a major role in reducing deaths from this disease with with 95 percent of women with early stage ER-positive surviving more than five years since their diagnosis.

The challenge with ER-positive breast cancer, however, is that these breast cancers can come back years after ostensibly curative treatment. Recurrent ER-positive breast cancers are less likely to respond to the same therapy that was used to treat the primary breast cancer.

In recent years, we’ve seen the emergence of the CDK 4/6 inhibitors (palbociclib, ribociclib and abemaciclib) for metastatic ER-positive breast cancers. While these targeted therapies have dramatically improved survival for many patients, they don’t work for everyone and may stop working for those who received an initial benefit.  Efforts are ongoing to identify new combination approaches to improve response to CDK 4/6 inhibitors including new estrogen receptor - and androgen receptor-targeted therapies, novel drug designs, and new CDK-directed therapies.

HER2-positive breast cancer. For many years, breast cancers that were driven by the HER2 oncogene were considered lethal. The discovery of trastuzumab (Herceptin®) revolutionized treatment for HER2-positive breast cancers but not every patient receives the same benefit.

Since the discovery of trastuzumab, other HER2-targeting agents have emerged and now combination approaches using dual HER2 agents and chemotherapy are common. One of the challenges in the clinical management of HER2-positive breast cancer is knowing which patients diagnosed with early-stage disease need aggressive, i.e. dual targeted therapy or added chemotherapy, and which do not. Both of these scenarios come with added toxicity and significant cost (in the case of adding a second HER2 agent).

Unlike ER-positive disease in which doctors can utilize results from the genomic test: Oncotype DX™ to determine the efficacy of chemotherapy for a particular patient, HER2-positive disease doesn’t have a similar test to guide treatment decisions.

Neoadjuvant therapy (therapy delivered before surgery) has emerged as a way to gauge the aggressiveness of a HER2-positive breast cancer. For patients whose tumor responds well to neoadjuvant therapy, a less aggressive treatment regimen may be all that is needed. While those whose tumors do not respond, may require more aggressive treatment.

In addition to personalizing the approach to treatment in HER2-positive breast cancer, new drug designs including drug-antibody conjugates, such as ado-trastuzumab emtansine (T-DM1) are improving the precision and effectiveness of HER2-targeted therapy.

Triple negative breast cancer (TNBC). Triple negative breast cancers are so named because they lack estrogen, progesterone and HER2 receptors.  Combination chemotherapy is still the standard treatment for early-stage TNBC, and many patients respond well to this approach. As in HER2-positive breast cancer, the tumor’s response to neoadjuvant therapy can inform subsequent adjuvant therapy.

Recent results from tumor profiling studies have shown that TNBC is a family of breast cancers and this is opening the doors to new targeted approaches to benefit patients with certain types of TNBC:

- Immunotherapy: Early this year, the FDA approved the first immunotherapy in breast cancer, specifically for patients with advanced triple negative breast cancer. Results from the IMpassion 130 trial demonstrated a significant benefit of atezolizumab, a drug that targets a protein called PD-L1. Again, not all patients benefit from this therapy and efforts continue to improve immunotherapy for TNBC, including vaccine development, combination immune- and immune enhancing therapies. Read more about the IMpassion130 trial in our earlier blog featuring an interview with Dr. Leisha Emens.

- PARP inhibitors: Last year, the FDA approved the first PARP inhibitor, olaparib, for TNBC that are driven by mutations in the BRCA1 or BRCA2 genes. Most breast cancers caused by inherited BRCA mutations are the triple negative subtype. Mutations in these genes cause a defect in a type of DNA repair called homologous recombination (HR). This defect makes the cell dependent on a backup DNA repair process that is regulated by a protein called PARP (Poly (ADP-ribose) polymerase). Combining a PARP inhibitor with DNA damaging chemotherapy kills cells that harbor mutations in the BRCA genes. Efforts are ongoing to understand why some tumors respond to this approach and others don’t, or why tumors become resistant. This is opening the door to new strategies including immunotherapy combinations with PARP inhibitor therapy.

- Selected Androgen Receptor modulators (SARMs):  While the androgen receptor (AR) emerged as a target in prostate cancer, it is not uncommon to find AR on TNBC tumors. Clinical and laboratory studies are ongoing to test the efficacy of AR inhibitors for some patient with TNBC.

BCRF Co-Scientific Director Comments on New Genetic Testing Recommendations for Newly Diagnosed Breast Cancer Patients

 

Below is a statement from BCRF Co-Scientific Director Dr. Judy Garber

The American Society of Breast Surgeons has called for genetic testing to be offered to all women diagnosed with breast cancer.  Their action stems from a concern that many criteria set by insurers or other guidelines will miss some women who either have little family history or are not aware of an accurate family history that would identify their risk, or have a less typical history that would call attention to their risk of carrying genetic risk.  They recommend that all women have “panel testing” so that all breast cancer-related genes will be examined.

Genetic testing has changed in major ways from the early days. It is much less expensive, technically much more comprehensive and accurate, and much more widely available.  The results of a genetic test can have important impact on the care of women at their cancer diagnosis, by informing surgical decisions, and on their overall care by identifying women who should have their ovaries removed at some point, so that they do not survive their breast cancer only to die from avoidable ovarian cancer. 

There are also important implications for their family members, who can learn that they either do, or importantly, do not share a cancer gene mutation that places them at increased risk of breast and certain other cancers, so that they can obtain proper surveillance and preventive care.  One could argue that better genetic information could help reduce the rate of bilateral mastectomies among women who do not have as much risk of a second breast cancer as they fear.

Nonetheless, the recommendation is controversial at this moment. Their data that supports their concern about missing mutation carriers is real, and that people do not recognize their possible genetic risk, especially when the history is on the father’s side, or there are few female relatives who could have had cancer, or ovarian cancer or pancreatic cancer is mistaken for stomach cancer, for example. 

Individuals of Ashkenazi Jewish descent are often unaware that their risk of carrying the specific “founder” mutations in the BRCA1 and BRCA2 genes is tenfold higher than the general population. However, there is concern that most surgeons are not equipped to provide genetic evaluation for their patients with sufficient back up to make sure that the testing is provided with care, and that the chance of incomplete counseling in any but the most straightforward cases is concerning.

The testing laboratories do often have genetic counselors to help address the general shortage of genetic counselors who might be available to surgeons outside of academic practice, but and even there, the availability of counselors is variable.  Also, not all genetic test results are straightforward, so that it will be necessary for there to be resources after testing to help explain the results to the patients, but also to their providers. If they are to provide genetic testing, surgeons will have to take responsibility for understanding the differences among genes so that they provide appropriate and nuanced care. If they order the test, they must be prepared to understand the important implications as well as limitations of the technology, as they do for all other tests and decisions they make for their patients. 

Genetic information is powerful, and all women with ovarian cancer are already encouraged by guidelines to undergo testing for treatment implications.  We are moving to that space in breast cancer, and the ASBS would like to hurry us along.  We agree that increased awareness of genetic risk that could affect the care of a woman with breast cancer, and ultimately also the management of her family members, is a good thing. 

We would support more women being offered the opportunity for genetic evaluation, including women with breast cancer, but also endorse the provision of that information with adequate supportive care throughout the process.  We want to make sure that women understand still that genetic testing is an option, not a requirement, and that there are ways for them to have questions answered before they decide that they must be tested at the time of diagnosis, If for no reason other than that insurers are not paying for all women at this time.  We do believe that knowledge is power, but also that women should have some control over how and when they obtain genetic knowledge, even if they can’t control the result of the genetic test.

Why Patient Engagement is Critical to Breast Cancer Research

 

Researchers and patients share a common goal: to accelerate breakthroughs to save lives. Clinical trials are where these two groups can work together towards this collective objective. At the AACR Annual Meeting held March 29 through April 3 in Atlanta, BCRF researchers discussed how scientists can better engage patients throughout their projects. The conference, attended by thousands of scientists from around the world, covers the latest discoveries across the spectrum of cancer research.

BCRF investigators Dr. Elizabeth Jaffee and Dr. Nikhil Wagle participated in a panel titled Engaging Cancer Patients as Partners in Research with Drs. Gregory Simon, Paul Kluetz and Louis Staudt alongside patient advocates Danielle Leach and Vernal Branch. They discussed the importance of including cancer patients’ data and input in the research process.

Patient engagement is the “blockbuster drug of the twenty-first century,” Dr. Elizabeth Jaffee said pointing to how it can reduce disparities and inform survivorship science.

Involving patients from the start

However, while researchers see the value in empowering patients throughout the research process, there are major challenges that lie ahead. Currently, less than three percent of cancer patients participate in clinical trials.

In order to increase accrual, researchers agree putting the patient at the center of clinical trial design can lead to trials that will both engage patients and benefit them the most. This can be seen in not only improving a patient’s longevity but also giving them the opportunity to live the best life while living longer. This is where patients can truly impact the research process.

Breaking down barriers

Even if trials are well designed, not all patients may be able to participate, because of eligibility criteria or distance from the clinical trial site, Dr. Nikhil Wagle pointed out. That’s why he founded Count Me In, a nonprofit designed for patients in the U.S. and Canada to share their information with the research community.

Supported in part by BCRF, Count Me In was created to encourage patients to share their data in an easy and accessible way. The initiative curates data from surveys, medical records, genetics, and more into a database that is deidentified and made available to the broader research community. Dr. Wagle now has over 6,000 patients across the U.S. and Canada enrolled.

During the question and answer portion of the panel, a current patient stated how important it was for her to participate. It gave her a sense of accomplishment and that she could make an impact in cancer research.

By involving patients in the research process, investigators hope to help create a more integrated cancer care and research system that can impact patients from diagnosis through treatment, remission and even prevention. BCRF is proud to support this collaborative effort that will lead us one step closer to the end of breast cancer.

BCRF and The Estée Lauder Companies’ Artifacts Accepted into the Smithsonian’s National Museum of American History

 

BCRF proudly joined The Estée Lauder Companies’ (ELC) Breast Cancer Campaign to donate several artifacts representing breast cancer awareness and philanthropy to the Smithsonian’s permanent collection at the National Museum of American History (NMAH).

“We hope these artifacts will long serve as a testament to visionaries like our founder Evelyn H. Lauder who worked tirelessly to end breast cancer,” said Myra Biblowit, President and CEO of the Breast Cancer Research Foundation at the ceremony.

The additions to the museum’s collection are particularly meaningful this Women’s History Month as Evelyn H. Lauder’s indelible mark on the trajectory of breast cancer research to save lives and improve women’s health around the world, officially joins American history. Items will also be included in the NMAH long-term exhibit, “Giving in America.”

Myra Biblowit and Bari Seiden-Young, ELC Vice President of Global Corporate Communications, Citizenship & Sustainability, joined David J. Skorton, Secretary of the Smithsonian Institution, Anthea Hartig, NMAH Director, and Abbe Raven, BCRF Board member and NMAH Board Chair, for a poignant ceremony signing the artifacts over to the Smithsonian’s permanent collection.

“Health and medicine have long been central to philanthropy and its expansive reach,” said Amanda B. Moniz, the museum’s David M. Rubenstein Curator of Philanthropy.

“Diseases cross borders and so do the means to tackle them, and, as a result, medical philanthropy has connected Americans to a global effort. Many Americans are inspired to give to medical causes because they hope to find a cure for a loved one or honor someone who has passed. Whatever the reason, these gifts contribute to medical ecosystems around the world.”

The philanthropy initiative also hosted its annual symposium, “Power of Giving: Philanthropy’s Impact on American Life.” BCRF Honorary Chairman and ELC Chairman Emeritus Leonard A. Lauder joined Co-Scientific Director Dr. Larry Norton and BCRF Ambassador Amy Robach to discuss “25 Years of Breakthroughs” and the progress made possible by philanthropy on breast cancer research over the last 25 years.

Currently on display in the “Giving in America” exhibit

A 2018 U.S. Mint Breast Cancer Awareness commemorative coin and Estée Lauder Companies’ “Count Me In” petition with a pink ribbon and the 2012 entry into the Guinness Book of World Records for the Estée Lauder Companies’ Global Landmark Illuminations Initiative, lighting landmarks around the world pink to raise breast cancer awareness, joined other objects that highlight the myriad ways Americans contribute to humanitarian aid and medical research in the NMAH “Giving in America” exhibit. “Giving in America” is a long-term exhibit that looks at philanthropy’s role in shaping the United States.

Donated to the Smithsonian’s Permanent Collection

An Estée Lauder Companies’ “Count Me In” petition with a pink ribbon from that first year will be added to the national collections along with a Breast Cancer Awareness donation card with enamel pink ribbon from October 1993; a Breast Cancer Research Foundation press kit, also from 1993; and, an Estée Lauder pink ribbon makeup compact from 1997. The Breast Cancer Research Foundation donated three proof coins from the commemorative coin program: a $5 pink gold coin, a $1 silver coin and the half-dollar coin made of copper-nickel. Authorized by law, the coin prices include surcharges on each coin that raised more than $1.1 million to benefit BCRF, furthering breast cancer research.

For more on the Philanthropy Initiative, visit http://americanhistory.si.edu/philanthropy and the Giving and Health Webpage at https://s.si.edu/GivingHealth.

Longtime BCRF Volunteer Shares Her Connection to the Cause

 

When Cathy Kerrigan woke up from her mastectomy surgery, her older sister Peg was the first person she saw.

“You look beautiful. You don’t even look like you had surgery,” Peg said.

Seven years later, Cathy still remembers this moment clearly. She credits Peg’s support for giving her a sense of peace every step of the way. 

“I remember thinking, ‘It’s because of you, Peg, I’m okay,’” she says. “She was really a rock.”

Months before her surgery, Cathy learned she was a BRCA2 carrier. She immediately turned to her older sister for guidance. At the time, Peg was BCRF’s Deputy Director and Chief Program Officer where she managed the organization’s multi-million dollar grant program.

“Peg made me feel like I didn’t have to panic.” Cathy says. “We were doing this together.” 

The sisters met with BCRF researcher Dr. Elisa Port who helped explain Cathy’s breast cancer risk. While Cathy didn’t have detectable disease at the time, she decided to undergo preventative surgery to reduce her risk of developing breast cancer in the future.

“I had an 84 percent chance of developing breast cancer by the time I was 70 years old,” she said. “I couldn’t live with those odds.”

Breast cancer had already impacted their family. Years earlier, one of Cathy and Peg’s younger sisters had been diagnosed with breast cancer. Later, the disease metastasized. However, her current treatment has kept the cancer at bay. She currently has no evidence of disease.

“We’re forever grateful,” Cathy said.

Cathy and Peg grew up surrounded by science. Their father was a cardiologist who became the town doctor in their hometown of Mechanicville, New York. While Peg’s career took her to BCRF, Cathy became a NICU nurse.

“I always looked up to Peg,” Cathy says remembering their childhood. “She’s always been a leader.”

The sisters are six years apart – which felt like an eternity during childhood – but today they share strong bond.

After Cathy learned her BRCA2 carrier status, BCRF researcher and renowned geneticist Dr. Mary-Claire King and her colleague Jessica Mandell, a genetic counselor, approached her family to see if they would be interested in participating in a study about inherited breast cancer risk. Cathy jumped at the opportunity to participate. Many of their relatives have followed suit.  

For Cathy, scientific studies like this one will help other families manage their risk.

“If there’s anything I can do to further research so future generations don’t have to deal with breast cancer, then I will,” she says.

Outside of her scientific contributions, Cathy gives back every year by lending her calligraphy talents to write escort cards for BCRF’s fundraising events. It’s a hobby she developed in ninth grade after her teacher fostered her aptitude for the art.

“I’ve always enjoyed it,” she says describing how she writes up to 1,100 escort cards ahead of the Foundation’s major fundraising events. For Cathy, it’s an easy way to contribute to the BCRF community.

“As a former nurse, I strongly believe research will make the difference in understanding and effectively treating breast cancer,” Cathy says. “For me, supporting BCRF is a no-brainer. It’s where our future lies.”

How Math is Unraveling Mysteries Behind Breast Cancer

 

Throughout human history, mathematical approaches have consistently driven the discoveries that advanced civilization. In an effort to better understand breast cancer from all angles, BCRF launched the Mathematical Oncology Initiative in 2017 which brings together mathematicians and computer scientists with biologists and oncologists.

“Mathematics has been fundamental to medicine and oncology for decades,” said BCRF researcher Dr. Allen Tannenbaum whose project belongs to the initiative. He cites the Norton-Simon Hypothesis as a modern example which impacted many lives through a model supporting different chemotherapy schedules.

“New mathematical models, however, are more comprehensive and can be used to study the underlying biology of cancer,” added Dr. Joseph Deasy.

Drs. Deasy and Tannenbaum joined forces five years ago with the goal of applying new mathematical tools to better understand the evolution of cancer – the changes that occur during its progression – as well as what makes one cancer different from another.

“While other methods [such as DNA sequencing and protein analysis] are helpful in pinpointing molecular changes in a cancer from one point to another, mathematics can create a continuum of points and keep track of them through time,” Dr. Deasy explained.

They call their method “high dimension systems analysis” (HDSA). This is where they compare the entirety of a complex system – for instance two tumors – and identify what is different about them. This is often the level of genes or proteins, which may drive or suppress tumor growth

Their expectation is that HDSA can identify patients more or less likely to respond to specific drugs. More importantly, it allows the scientists to identify changes that occur when new things are introduced into the system, such as chemo, radiation therapy or targeted therapies. This in turn can inform the causes of drug resistance and provide insights into more effective treatment approaches.

Computational methods like HDSA accelerate discoveries that can then be tested in biological systems and in clinical trials. Drs. Deasy and Tannebaum have confirmed that their methods work using existing cancer datasets and will soon publish results describing a new subtype of breast cancer identified using their HDSA methodology.

In their next phase of research, the team will work on integrating results from HDSA, i.e. changes that occur during the evolution of the tumor, to information obtained from tumor images through machine learning technologies.

“With BCRF support, we hope our method will evolve, merge with other technologies and provide more precise and predictive information in a clinical setting,” Dr. Deasy said. 

International Women’s Day: A Conversation with BCRF Researcher Dr. Julie Gralow

 

Dr. Julie Gralow is an international researcher who has focused on issues of global health for much of her career. A BCRF and Play for P.I.N.K researcher since 2002, we turned to her this International Women’s Day for her perspective on the successes and continued challenges in women’s health worldwide.

Among her leadership roles in the oncology community, Dr. Gralow participates in the Fred Hutch-Uganda Cancer Institute collaboration training Ugandan oncology fellows. She has led efforts globally in breast cancer advocacy, including founding a global women’s cancer advocacy network, the Women’s Empowerment Cancer Advocacy Network (WE CAN), to support cancer survivors and advocates around the world. She is co-chair of a global campaign called the Breast Cancer Initiative 2.5 (BCI2.5) Secretariat, aimed at reducing disparities in breast cancer outcomes.

Last year she was the recipient of the Humanitarian Award from The American Society of Clinical Oncology for her ongoing global work.

BCRF: What do you think is the greatest global achievement in women’s health in the last decade?

Dr. Gralow: Far fewer women are dying in childbirth. World Health Organization estimates show a more than 40 percent decline in deaths related to childbirth between 1990 and 2015. This is a significant accomplishment, but with that success comes new challenges. These women are now living longer to get chronic diseases, including breast cancer.

As developing countries are becoming more modernized, we are seeing an increase in the lifestyle-related risk factors associated with breast cancer. A more sedentary lifestyle, lack of exercise, poor diet, and access to fast food are contributing to an increase in global obesity. New opportunities for women such as education and employment have resulted in women delaying first pregnancy and choosing to have fewer children, but both of which can contribute to an increased risk of breast cancer. So, while we’ve seen great success in empowering women, it comes at a cost in westernized lifestyles and breast cancer risk, which many developing countries are ill-equipped to deal with.

BCRF: Breast cancer is the leading cancer diagnosed in women worldwide. Can we change that?

Dr. Gralow: In many of the low- and middle-income parts of the world, we’ve seen an increase in breast cancer awareness and, in some settings, access to breast cancer screening, mostly through clinical exam and in some cases mammography. That is an improvement and a success, but the more access to screening there is the more breast cancer diagnoses we’ll see. Perhaps the more important question is can we reduce deaths from breast cancer.

Early detection, with access to a diagnostic workup when a breast abnormality is first identified followed by prompt treatment, is more important than population-based screening, particularly in countries with fewer resources. We’ve seen a tremendous reduction in breast cancer deaths in the U.S. but that is attributably to not only early detection, but also access to treatment. If a woman doesn’t have access to affordable treatment, early detection is not going to reduce deaths.

BCRF: What are some of the challenges in improving breast cancer outcomes globally?

Dr. Gralow: Poverty, awareness and fear. If we can reduce poverty, we can have a huge impact on breast cancer outcomes. Costs and access to health care are huge barriers to adequate care in rural and low-income areas. A woman may have to decide whether she is going to feed her family or go to the doctor, and she may have to travel long distances.

She may fear the stigma or fate of her family if it became known she has breast cancer. In some remote villages in Africa for instance, there are prevailing myths that cancer is a family curse or that the disease could spread to others in the village, causing a family to be evicted from their community. In many remote parts of the world, women don’t survive breast cancer, so a woman may see no benefit to seeing a doctor until she is in pain.

BCRF: What are some success stories in addressing these challenges?

Dr. Gralow: On my first trip to Uganda in 2010, I met a group of women who had formed a women’s cancer support group called Uganda Women’s Cancer Support Organization (UWOCASO). These were women who had survived breast cancer and were speaking with newly diagnosed women to help dispel some of the myths about breast cancer. Over the years, I’ve seen the group evolve. The have earned the respect of physicians and have become an integral part of the continuum of cancer care. We held our first WE CAN Africa (Women's Empowerment Cancer Advocacy Network) conference in Uganda in collaboration with UWOCASO in 2013. They are making a major impact providing support, overcoming stigma, creating awareness, and improving care for women cancer patients in their country.

BCRF: Is there anyone who epitomizes International Women’s Day for you?

Dr. Gralow: Gertrude Nakigudde, UWOCASO Chief Executive Officer. Gertrude is a 16-year cancer survivor and a founding member of UWOCASO. She left her job as an accountant to do breast cancer advocacy full time. Gertrude and all the women of UWOCASO and similar support groups in Eastern Africa and throughout the world are heroes.  They are making a major impact providing support, overcoming stigma, creating awareness, and improving care for women cancer patients in their country. Recognition of the important contributions of cancer patient advocates in Uganda has led to Gertrude recently being elected to the Board of the Uganda Cancer Institute. 

Triple Negative Breast Cancer: New Study Highlights the Promise and Challenges of Immunotherapy

 

To understand triple negative breast cancer, we first have to understand how breast cancer is classified. Breast tumors are broadly classified into three major subtypes: estrogen receptor (ER)- and/or progesterone receptor (PR)-positive, HER2 receptor positive or triple negative.

Triple negative breast cancer (TNBC) is defined by what it’s not. The tumor cells do not express either of the hormone receptors, or the HER2 receptor. About 10-15 percent of breast cancers are triple negative, including many hereditary breast cancers that are driven by mutations in the BRCA1 or BCRA2 genes.

TNBC is a devastating disease, and this is compounded by a lack of targeted therapies. Triple negative breast cancer research is a major focus for BCRF. This past year, BCRF is supporting more than $15 million research in triple negative breast cancer.

This research has led scientists to discover that TNBC is more likely to respond to immunotherapy than other types of breast cancer, but response rates are still low. Being able to predict which patients are likely to respond is key to the success of immunotherapy.

On Triple Negative Breast Cancer Day, we highlight promising results from a recent study and how it may impact those with metastatic triple negative breast cancer. 

Immunotherapy shows promise for patients with triple negative breast cancer.

The study, led by BCRF investigator, Dr. Leisha Emens, may change the standard of care for some patients with metastatic triple negative breast cancer.

As reported in the New England Journal of Medicine, adding the immunotherapy drug, atezolizumab, to chemotherapy improved survival of patients with advanced triple negative breast cancer compared to chemotherapy alone, specifically in patients whose tumors had high amounts of the immune checkpoint protein PD-L1.

“Immunotherapy is revolutionizing cancer therapy across multiple tumor types,” Dr. Emens said at the 2018 San Antonio Breast Cancer Symposium where she presented new data from the IMpassion 130 trial.

“The breakthrough came with the discovery of the PD1 pathway.”

What is PD-1?

The PD1 receptor forms a bond with a partner protein called PD-L1, thereby shutting down the immune response. Tumors may hijack this system by increasing PD-L1 production in the tumor microenvironment, effectively shutting down the immune response.

Anti-PD-L1 therapy, like that used in the IMpassion130 study, prevents PD-L1 and PD1 from forming a bond and allows the T-cells, the smart bombs of the immune system, to seek out tumor cells and kill them.

The Study

IMpassion130 was the first international, randomized, placebo-controlled, double-blind Phase III trial that demonstrated clear benefit of immunotherapy in selected patients with metastatic triple negative breast cancer.  In addition, it identified a marker to identify those patients most likely to benefit.

The trial, which included BCRF researchers Dr. Hope Rugo, Dr. Eric Winer and Dr. Sherene Loi in addition to Dr. Emens, enrolled 902 patients with advanced triple negative breast cancer who had not received prior treatment for their metastatic disease. All patients received Abraxane® (nab-paclitaxel) as standard chemotherapy; half received the PD-L1 drug atezolizumab in addition to chemotherapy while the other received chemotherapy plus a placebo.

The trial investigators compared progression-free survival–PFS (the time between start of therapy and when the tumor growth increases or spreads) –between the group that received atezolizumab plus chemotherapy and the group that received chemotherapy plus placebo. In both the overall population and in patients with high PD-L1 tumors, adding anti-PD-L1 therapy to chemotherapy had a significant improvement in PFS. In patients with high levels of PD-L1 in the immune cells around the tumor, PFS was increased from 5.0 months to 7.5 months.

In the first interim analysis of overall survival (OS), the trial investigators found that the addition of anti-PD-L1 therapy to chemotherapy increased OS from 15.5 months to 25 months, also specifically in those patients with high PD-L1 levels.  Together, these findings identify PD-L1 as a predictive biomarker that should be used to select patients most likely to benefit from this combination therapy, as the PD-L1 negative subgroup did not benefit from the addition of immunotherapy to chemotherapy.

“This is a significant improvement in this subgroup of patients,” noted Dr. Emens. “We believe this trial has identified a new standard of care for first-line therapy for metastatic triple negative breast cancer patients with PD-L1+ disease,” she said.

Challenges ahead

While there is much excitement about the results of IMpassion130, there are still many challenges to making immunotherapy effective in a wider range of breast cancer patients.

Dr. Emens explained that IMpassion 130 involved patients who had not received prior therapy for metastatic or locally advanced TNBC. Efforts are ongoing to develop approaches for effective immunotherapy later in the course of therapy as well as in the neoadjuvant (pre-surgical) setting for early-stage breast cancer.

Efforts are also ongoing by Dr. Emens and others to develop alternative strategies for PD-L1-negative breast cancer patients that may include vaccine or other approaches in addition to anti-PD-L1 therapy.

Watch the full interview with Dr. Emens below.

BCRF Supporter Turns New Year’s Eve Celebration into Meaningful Fundraiser

 

Holden Rosen Grupp has always enjoyed being a host. From sleepovers to team meals and holiday dinners – he grew up as an amateur event planner. So, when his favorite holiday, New Year’s Eve, was approaching he decided to turn the annual celebration into a fundraiser for breast cancer research.

“I wanted to take advantage of the organic hype that comes with New Year’s Eve, and put that excitement towards raising money for a great cause,” Holden said. Now in its second year, the event raised $25,000 for BCRF.

Holden found BCRF through his friend, Stephanie Ginsberg, a dedicated BCRF supporter and Advisory Board Member.

“I needed to find an organization that I trusted. Once you learn about what BCRF is doing, there are few organizations held to such a high standard,” Holden said.

Holden knows the power of research firsthand. Mothers of several of his close friends and most recently, his cousin, have been diagnosed.  

“I’m inspired by the people I know who have fought this disease with a smile on their face,” Holden said. “When you have a personal stake in this game, your passion and support is accelerated.”

Holden’s idea for the New Year’s Eve party blossomed from an event he organized in high school for 250 people. This year, Holden adapted the event to take place at the Sound Lounge in the Flatiron district, which the location provided pro bono. United with the help of friends, they cleared out the space, decorated it and Holden even tapped an old resource to help with the entertainment: the band who played at his bar mitzvah.

“It’s really gratifying to see a bunch of young adults who don’t really know what to expect, step out of their comfort zone in support of BCRF,” Holden said “There were a ton of people who helped make this happen.”

With the success of his fundraiser, and more like them, he strongly believes these efforts will advance critical research. 

“I think that breast cancer will be the first form of cancer cured,” Holden said. “More so, I am hoping that it will be a stepping stone to finding more cures, for other diseases, sooner rather than later.”

 

BCRF Partners with Springer Nature to Improve Data Sharing

 

A key tenet of BCRF’s mission is to connect investigators around the world while giving them the freedom to pursue their most innovative ideas. Today, we’re proud to announce a new pilot program, in partnership with Springer Nature, to encourage and facilitate data sharing among researchers.

Submitting research results in scientific journals and presenting at major conferences allows the investigators from all over the world to review and comment on the work of others. It is a major form of communication within the research community.  What is missing from the results presented in publication and meetings, however, are the raw data– individual measures collected throughout the study and used to prepare the final reports. Sharing these data points with other scientists not only validates published research, but also allows scientists to ask new questions from the same data.

The new pilot project will help authors share their data in such a way that research can be made accessible, reusable and reapplied to fuel new innovation that can put an end to breast cancer. Dedicated editors from Springer Nature’s Research Data Support will help investigators that publish in npj Breast Cancer to catalogue, describe and share data that accompanies the research paper.

Sharing raw data allows scientists to access information that would otherwise be unavailable to them—inspiring new questions and spurring new findings. The Human Genome Atlas is an example of how data sharing can create new breakthroughs. The raw data from this years-long effort involving more than 11,000 patients and 33 types of cancer was made publicly accessible and has been crucial to a vast array of scientific breakthroughs, like discovering subtype-specific mutational burden of CDK4 (a target of a, now, FDA-approved drug).

Today, the amount of freely accessible data from published studies is limited, partly due to the resources and expertise that are required from the investigators to enable data sharing. In a unique partnership that started four years ago with the creation of the first online scientific journal dedicated to breast cancer research, BCRF and Springer Nature now take aim at breaking barriers that limit data sharing.

Through the support of BCRF, npj Breast Cancer is now setting the standard for the broader cancer research community and both partners are excited to learn more from this pilot.

Larry Norton, BCRF’s Co-Scientific Director and npj Breast Cancer’s Editor-in-Chief, said: “The provision of this service for all of our authors is in part a response to the calls for broader data sharing that have been gathering pace in the cancer research community.“

Good Things Come In Pairs: BCRF and Rothy’s Team Up to Celebrate Galentine’s Day

 

Valentine’s Day is just around the corner, but we’re also celebrating an equally important holiday dedicated to female friendship: Galentine’s Day. At BCRF, improving breast cancer outcomes by advancing the world’s most promising research lies at the core of our mission. That’s why we’ve teamed up with our corporate partner Rothy’s to commemorate this special day and highlight the power of a great gal pal. Rothy’s dedication to women’s health has fueled over 400 hours of research.

“Joining BCRF as a partner felt like the perfect fit – we are honored to support a cause that aligns with our commitment to helping women feel strong, comfortable and beautiful," said Kerry Cooper, President & COO of Rothy’s.

Last October, Rothy’s gave customers the opportunity to gift a pair of pink flats to a woman in their lives who had been impacted by breast cancer. The response was overwhelming: 2,200 stories were submitted, and 2,200 women received a pair of the signature flats. To pay tribute to the women who shared their experiences, Rothy’s also chose to support lifesaving research and made a $22,000 donation to BCRF.

"The thousands of stories shared by the loved ones of breast cancer survivors during our Breast Cancer Awareness Month gifting event inspired us to take action in their honor,” said Cooper.

That’s why we’re celebrating the power of female friendship with Rothy’s this Galentine’s Day. 

During BCAM, one of these powerful stories Rothy’s received came from two best friends living in Boston. Katie nominated her friend, Meena, who had been in remission from breast cancer for four years. An ICU nurse at Children’s Hospital Boston, Meena remains grateful for the medical team who helped her during treatment.

“From volunteering at her kids’ school to serving on the board of a foundation that provides heart patients and their families with tremendous resources, Meena is always giving back,” said Katie.

“She has a knack for making everyone around her feel special. Gifting a pair of shoes to her is the least I can do!”

In the spirit of Galentine’s Day, we’re proud to join forces with Rothy’s. By celebrating these strong women, we’re shining a light on the powerful role friendship plays for all of those impacted by breast cancer.

To learn more about Rothy’s and to read the stories shared by loved ones of breast cancer survivors, click here.

Run with Team BCRF in the 2019 TCS New York City Marathon

 

Team BCRF TCS New York City Marathon

For the eighth year in a row, BCRF has 10 spots in this year’s TCS New York City Marathon on November 3rd. Each season, we are honored to have Team BCRF runners take on the challenge of participating in this monumental race to support breast cancer research.

For those interested in applying to be on Team BCRF in the 2019 TCS New York City Marathon, please fill out the application form and take note of the conditions below.

Each participant is required to raise a minimum of $3,000 for BCRF. In return, the race entry fee will be waived and each runner will be provided with a Team BCRF shirt, as well as pink ribbons and bracelets to advance their fundraising efforts.

All applications must be received by April 1, 2019 and will be reviewed on a first come first serve basis. The names of selected runners will be announced no later than April 12, 2019.

For any additional questions, please email Christine Ward at cward@bcrf.org.

Investigating Breast Cancer: Dr. Sofia Merajver

 

Subscribe to BCRF Conversations here:

As you’ll hear, Dr. Merajver – who has been a BCRF Investigator since 2004 – discusses her unique, collaborative and extraordinarily human approach to one of the most significant science questions of our time: How to find new strategies for the prevention and treatment of metastatic breast cancer.

Why “unique approach?” Well, it’s not just her science and the way she connects seemingly disparate disciplines to all focus on a single goal. It’s also about the way she views her life’s calling – and applies that view to medicine. As she says in the conversation: “A tumor doesn’t walk into my office; a whole person walks into my office.”


Read the transcript below:

Chris Riback:  I’m Chris Riback. This is Investigating Breast Cancer, the podcast of the Breast Cancer Research Foundation and conversations with the world’s leading scientists studying breast cancer prevention, diagnosis, treatment, survivorship and metastasis.

And that’s what we’re discussing today – in a way and tone that, frankly, I didn’t fully see coming.

Dr. Sofia Merajver is a professor of Internal Medicine and Epidemiology at the University of Michigan, where she is also Scientific Director of the Merajver Breast Cancer Research Program and Director of the Breast and Ovarian Cancer Risk Evaluation Program.

As you’ll hear, Dr. Merajver – who has been a BCRF Investigator since 2004 – discusses her unique, collaborative and extraordinarily human approach to one of the most significant science questions of our time: How to find new strategies for the prevention and treatment of metastatic breast cancer.

Why “unique approach?” Well, it’s not just her science and the way she connects seemingly disparate disciplines to all focus on a single goal. It’s also about the way she views her life’s calling – and applies that view to medicine. As she says in the conversation: “A tumor doesn’t walk into my office; a whole person walks into my office.”

This is a view Dr. Merajver clearly held even before going through breast cancer treatment and care herself, an experience, she explains, helped change the vocabulary she uses – the way she talks – with her own patients.

And a heads up: You’ll want to hear the very, very end of this podcast and the inspirational way Dr. Merajver ends every conversation with her patients. It’s exactly what breast cancer research – and medical care generally – is about.

Dr. Merajver, thank you for your time.

Dr. Merajver:  You're welcome. It's a pleasure to be here.

Chris Riback:  I didn't have to spend very much time researching about you to get what I think must be a clear sense about the type of scientist and physician you are. In fact, there's one line on your research program webpage that I believe, gives it away, where you write and I'm quoting "We do not turn anyone away, nor do we think any case is hopeless before we start." Does that sum up your core philosophy?

Dr. Merajver:  Yes, this is definitely operationally how we run it ... how I run it and that is I like to think of a patient as a whole person. A tumor doesn't walk into my office, a whole person walks into my office with everything she or he has experienced in his or her whole life.

And they have specific concerns. They have specific goals. They have dreams and aspirations. They've had tragedies. Everything bears into what's going to happen, and we know very little about how to tailor therapies from a biological perspective, to how stressed or how happy or how relaxed somebody is.

We don't know how to do that, but we can understand a person. And discuss things with that person about what is likely to happen with different therapies. And how they are likely to cope with it, and who is home with them and bring them to the treatments. And, what are their goals?

Is there a special trip they want to take for six months or is there a wedding coming up. These little things are very important to us in our lives and I think to be a good doctor, or at least to try to be as good a doctor as one can be. You need to really give everyone a chance.

First of all you can't give up on anybody without knowing about their tumor more or about their biology and also about what's happened to them before. Yes, it has served me well for quite a few years, so I continue to do that.

Chris Riback:  It certainly has for a number of years and the impact that you've been making. How do patients react to that approach and your level of humanity? Does it surprise them? I'm sure they appreciate it but from what we all have positively and negatively experienced in life. That might not be what they expect immediately from somebody who specializes in internal medicine and epidemiology.

Dr. Merajver:  Well, I think I try to give the care that I would like for my family members, for myself. When you do it that way, it becomes ... When your job is so close to life or death, then you have a responsibility to give it everything you've got.

And not just that part of your brain that remembers facts and figures and names of drugs, and lists of side effects and the shape of cancer cells. But the other part of the brain that puts it all together and tries to predict what's likely to happen to this person, given his or her circumstances today.

And that requires knowing the person. Practicing medicine has been nothing but an incredible privilege and pleasure for me and I'm very lucky to have been able to have a career I have and combining a passion for science and to bring it to the patients.

It's just an unbelievable privilege and sure, it took some sacrifices, but I don't see them as sacrifices. I see them as just basically what it takes.

Chris Riback:  That's a wonderful characterization, and I'm sure that your patients feel like ... people who benefit from your research, feel like they are the ones who have gotten the benefit and for whom the privilege is.

Let me ask you, if I could about the science because that's the areas in where you are clearly just, and listening to you where you are putting both your heart and your mind ... the science is ... those are the discoveries that you're making. And to understand your work, it's first imperative I believe, to understand metastasis.

Before we get into a little bit of the nitty gritty around your studies and the research. How do you explain to people, not only what metastasis is, but why it happens? And why that, in some cases, cancer cells in one part of the body travel to other parts, yet in many other cases this never happens at all?

Dr. Merajver: Indeed. Cancer, basically all cancers have with possibly just one exception, a savvy capability of eventually going to distant organs. Some cancers do that more easily than others, and some cancers prefer distant organs over others.

The science of metastasis has exploded over the last 40 - 50 years. And we know an awful lot about the individual steps that a cancer cell has to cope with. And it isn't an easy trip. Let me assure you.

The amazing thing about cancer is how hard it is for the cell to really make it. And how powerful the adaptions ... how the cancer cell has to constantly change or recruit other cells to help it, cope with a different parts of the body, has to travel through.

A tiny cell that is lodged in the breast tissue and it wakes up, saying it was left behind, or it evolved in the breast tissue, because we focus a lot on breast cancer. Not exclusively, but certainly most of our work is on breast cancer, a huge public health problem around the world. We figure we want to tackle, and we want to tackle the most aggressive cancers.

The ones that kill proportionately the most women. And a tiny cell is in the breast minding its own business and then there is a constellation of things that need to happen, for it to even begin to move in that little place that it is logged. And then to find the blood vessel ... to get inside the blood vessel.

The blood is not good for cancer cells unless this is a leukemia that is a blood cancer. Cancer that arise in organs like prostate and breast and pancreas ... Once they're in the blood, it's a very hostile environment. It's not easy for them to survive.

Most of them die there. Lucky for all of us and then our immune system also is able to recognize them more easily once they're in the blood, because a lot of immune cells also circulates through the blood. There is a real war that is being waged every single day in everyone of us.

Most of us feel that we have the potential to be developing little tiny cancers throughout our lives pretty much. Most of which don't seem to come and cause us any trouble. Now once the cancer is diagnosed in some organ ... even if it removed and then sometimes chemotherapy or hormonal therapies are given, there may be, even from the beginning, just a small ... we call them clones because they are all very similar to each other.

Clone of cells, group of cells that already have the potential to spread. And why do they in some cases and why don't they in some other cases? That is the really holy grail of oncology, in a sense that we all have theories, and we all have very detailed experimental models like I have in my lab and many other scientists ... the BCRF scientists have in their labs.

But we don't what I would call from the physics world a unified theory of a cancer cell. We don't have that. We are working towards that to really understand at a very broad ... what we call systemic level. If you take everything into account.

The cancer cell then the normal tissue where the cancer cell is right now, and then what else is happening in the body. Is this a patient who also has diabetes? Is this a patient who is also obese? Is this a patient who is eating vegetables? Is this a patient who is smoking?

Is he or she drinking too much? Are they seventy? Are they exercising? Are they stressed? Are they poor? Are they constantly concerned about where the next meal comes from? I think if the government shut down goes on for any longer, I think we should take ... we should do. We are missing on opportunity to do a research study on government workers because they are under tremendous stress right now.

The prediction would be that they would be some consequences. They may be related to cancer or to other diseases. People under stress don't do well in multiple chronic diseases and cancer is a chronic disease.

Chris Riback:  It's so interesting to hear you talk about this holistic approach and all the different angles and aspects in which you need to look at it. First of all, it for me, goes back to the beginning of this conversation and how you even just described in your role ... you need to think about all aspects of what's going on with a patient. It also, from what I've read, seems to be how you run your research lab. When your process ... One of the things that you're doing is, you're using devices to study which breast cancer cells can migrate to different tissues.

Dr. Merajver:  Yes indeed.

Chris Riback:  Your process ... you combine this theoretical view what do the models predict will happen with the actual experiments themselves. And to do this, you bring together Physicists, Electrical Engineers, Biological Chemists, Cell Biologists, Oncologists, more. How do you conduct that kind of orchestra?

Dr. Merajver:  That's what I love the most. I just have to tell you one minute why, and that is, I decided to be a scientist when I was five years old. This is what I announced to my parents. That's what I was going to be.

And, when you're five, what do you know what science is and what do you know about this specialty or that specialty? But I understood that what I was happiest at, is and asking questions and find answers. And if I didn't know the answers to ... research the answers.

And that time, of course, you couldn't Google everything. You actually had to go to the library and read something and think about that and then go again the next day, and so on. Anyway-

Chris Riback:  ... I remember reading-

Dr. Merajver:  ... Exactly. Holding something in your hand [inaudible 00:15:20]. It is through that process of wanting to be a scientist from such an early age, where the disciplines mattered very little to me.

I was just as interested as knowing what happened to Neanderthals, as I was interested in how to cure cancer. Although I had a very significance with cancer when I was 15 and my father came down with just about the worst kind of lung cancer a person can have.

I felt obliged to study a lot about that to see how I could contribute to his treatment. It's crazy for a 15 year old to have those aspirations. But I had already been thinking about science for 10 years by then, so was considering myself as semi expert, which of course pretty ridiculous.

But non the less, that is something that has carried me and even though I'm no longer 15, fortunately, I am able to talk to a large number of types of scientists. And just respecting their skills and getting them excited about cancer. Cancer needs all these scientists.

And BCRF is basically the only research organization that respects that importance of bringing engineers and quantitative scientists in really multi-disciplinary, constantly experiencing the cancer phenomenon. Take example artificial intelligence. For example, we are using artificial intelligence in our lab and to figure out which cancer cells are going to go into the brain.

That's a question that's never been tackled. If you had a small tumor. Nobody thinks of brain metastasis, but I do because I know a certain number of those little tumors will show up in the brain and they will carry the day for that patient.

The brain metastasis is a very serious metastatic event and people can survive it. A certain number of weeks to months, even sometimes years. But it is rare. The years is very rare, whereas metastasis is other sites, people can survive many years, especially from breast or prostate cancer and so on. But brain metastasis have a certain way of attacking who we are because obviously our personality and our feelings and our identity resides in our brain.

Brain metastasis are especially something I really have a specific penchant for trying to beat and this is something that worried me before I was a hysician. And once I was able to invent a way to take a small tumor and then see if there is some physical phenomenon about the cells because the blood brain barrier is a true barrier.

The whole country now is involved in a barrier question, right? And we have barrier. Until I started studying biology, we know a lot about barriers. And there are leaky barriers, there are semi leaky barriers and there are real impossible barriers.

The blood brain barrier can become a leaky barrier especially for certain cancer cells. But the question was never asked. And I just can't stand questions that are never asked, and I built this whole system, funded by VCRF to try to see how the cells go through, but then once I had the system going, which of course the Engineers building it with me ... They will realize that "Hey, in order to understand this, the cells are so different one from the other, even though they come from the same person ... we need artificial intelligence to try to figure out that they are too big."

If we look at 200,000 cells and each one is a separate experiment, then you need different methodologies in mathematics to really try to predict how do you really separate the ones that will go through from the ones that won't.

We had to use machine learning like the same thing that's used to predict the weather and so on, which are incredibly large data set and the motion of stars and planets in the distant galaxies. That's the kind of mathematics we're using to predict what's going to go in the brain.

But I'm not scared by any of this. I know math is good, and I have a PHD in Physics, but I am not the one doing all the machine learning. I couldn't do it either ... I'm not trained in that, but I can talk to other scientists and so we do have now, the capability for the first time in being able to predict by the shape and the behaviors of certain cells, whether they are likely to go into the brain.

And that's ... starting with a paper that's being reviewed right now, and it took about four years. You have to be willing to have a bit of a dry spell for that question so other things in your laboratory have to be producing papers and results because in most scientific laboratories you can't four years without a publication, or they'll think you are a complete failure.

Of course in the olden days, very famous scientists sometimes did go several years but that's not the pace of biology research today. When you talk about managing the orchestra, a lot of what I do is to steer the projects and manage the funding so that we don't run out of money for any of the projects, and that they are all producing results are a fast clip to keep up with the pace of science today.

Chris Riback:  That makes a ton of sense, and it also makes me think "Well in the old days we all used to read documents longer than a 140 characters in length." Whatever you can bring back from the past would be terrific.

I keep listening to you and the journey and the difficulty, and to use your word, the barriers around the movement of cancer cells from one location to another. You talked about the trouble of traveling through the blood except leukemia, cancer, and the challenges of metastasis in a cancer cell moving into the brain and yet we know it happens.

The predictive nature and that's at the heart of so much of what you do. Where would you say you are ... where would you say we are ... what do you day to patients around "Here is what I'm looking at as I think about predicting." I'm not in the predicting business." You might also say, but when I think about what might happen around metastasis. What do you know about predicting when and how metastasis can occur?

Dr. Merajver:  For an individual patient who doesn't have metastasis yet, the tools we use in the clinic are not quite obviously as complete and extensive as the tools we use in the laboratory. That's going to take a while to have a trajectory from the lab to the clinic, in a formal way.

We have a trajectory from the clinic to the lab in that we collect tissues from patients, and we do all this research, and then we refine these predictors and then we test them in the real world.

We're in the process of doing that next step, which is to test them in the real world in terms of over a broad range of patients, can we predict what their likely metastatic trajectory is going to be.

But I tell you something ... we are really exciting, which is really getting very close to the clinic. A few years ago I decided that I was very satisfied with the idea, that when we take a biopsy from a patient ... if the biopsy is sequenced that means the DNA is studied, and we find out the gene changes that that tumor has undergone. A large number of labs including a very well known lab here at the University of Michigan has been doing that, and they recommend then drugs for patients.

That was very unsatisfying to me in the sense that I thought this is a great first step, but in my mind I predicted that there would often be lists of drugs and how would the patient underactive, would choose what drug to actually give the patient.

We set out, also with help from BCRF ... we set out to build a whole platform, where we can take biopsies from the patients and test them for drugs in the laboratory in a manner that is consistent, rigorous reproducible.

All these important things that need to happen in a scientifically rigorous laboratory because this hasn't been attempted before, and the oncology has a very bad taste about drug testing of tumors because there were many companies that were reporting to be doing that.

They were not doing it correctly partly because they didn't know but then they shouldn't have been going commercial with that, but non the less that happened and some of my teachers in oncology would tell me it would never be possible.

But I never believed that because we are very advanced ways to culture cells directly from the patient. We are very excited that now we can actually test 20, 30, 40 drugs in a matter of days after a patient has a biopsy.

Then in addition to the drugs suggested by those studies that sequenced the DNA, which are incredibly useful, we are then able to perhaps in the near future be able to produce priorities. Patient is now going to take 20 drugs in succession and the question is "What about combining two drugs?" Which two should you combine and why?

We have the capability of testing combinations, testing single drugs and I believe that what I'm going to put the most effort in my lab in the next five years, to get to the point that we can work alongside those tests that are called genomic tests and be able to really help Doctors and patients.

Say "OK, your tumor can be killed by these five different drugs and these are the spectrum of side effects of these five drugs." And then they have something to discuss in the examining room. They have something to discuss about choices, because right now we are pretty much guessing or they are opportunistic matches.

If somebody has a mutation in a given gene and there happens to be a clinical trial open to a drug that may be related to that gene, then the patient gets put on that trial. There's nothing wrong with that because that's the best we can do now. But think we can do better.

We need to do better because we are only benefiting about two to five percent of the patients who are sequenced right now. And that's too low. We need to get to 80%. I want to get to 80, 90% in the next five to 10 years. I think we can be there.

Then in that landscape, working with many other Centers, I think we are looking at a horizon where in about 10 years, I think 80% of patients with metastasis can look forward to living years. I think that's the goal that is achievable. If we put funding into this and if we work together. It's a combination of things. It's not going to be just one lab doing everything.

Chris Riback:  Well, that certainly would be remarkable and no surprise that your mind is working in ways to bring together an orchestra of research labs, as opposed to just thinking that one instrument could do it all.

Dr. Merajver:  No.

Chris Riback:  I want to ask about you a little more as well. You spoke about this publicly. You are not just a breast cancer scientist and physician. You're also a patient.

Dr. Merajver:  Yes.

Chris Riback:  Does clinical and scientific experience and how does clinical and scientific experience apply to one's personal life when the one of the diseases that you've studied your whole life, you end up getting as well?

Dr. Merajver:  Yes, that's a bit of a detour on the road isn't it? I'm shopping for shoes on Michigan Avenue, Chicago visiting one of my daughters and from the time I chose the shoes until the time I paid for the shoes, I had cancer in both breasts.

That was just really not right. Anyway, that was a very unusual day and I'm incredibly fortunate. I have an incredibly supportive family and the hardest thing for me, was to tell my daughter who was right there. There was no way to fake it and then tell it under other circumstances. It was right there at their store on Michigan Avenue.

I'll never forget it but so she started crying, and it was very sad for me to see her so sad but it's an early stage and like all early stages, some have better biology than others. This is what I've done all my life. I know my biology, and it is what it is, and I have the best care here are the University of Michigan. Just unbelievable care.

For me, the experience as a patient has been extraordinary, and I hope every single patient we see here, has exactly the same experience. I also need to point out that I absolutely forbid my friends for doing anything out of the ordinary for me.

They were offering this and that and I said "No, I want to see you when you have clinic." "Oh, I'll see you on Saturday." "No, no, I want to come on the regular clinic day." I don't want to tall through the cracks because you are doing things out of the ordinary. Even though I'm a Doctor here and I've been here for many decades, I've got the same care anyone gets because I like that idea. I like the system. I like to get the care that every patient gets.

That's just a bit of advice to any listeners out there who are thinking "Well I can't get good care because I'm not a VIP." Don't try to be a VIP. Just make sure your Doctor cares about you and that you're connected to the clinic. You know the office number. You have a nurse or a scheduler at the clinic who's navigating your case and you keep all your appointments.

And bring a family member of a friend to take notes with you and so on. Just do ... just take care of yourself and the systems in America are good to cure patients who are aware more or less of the steps.

I went through all the steps for treatment and I really missed a week of work because I just tele-conferenced from my lazy-boy and I won't let cancer define my life. It's something that happened to me, but on everyday I am happening to cancer. I'm beating back cancer in all of my patients and I'm helping my colleagues do the same. I figure cancer got a week out of my life so far and made a bunch of the people I love the most very unhappy and I don't get that a lot, but other that I recovered that week.

Chris Riback:  That's terrific and yes, you've recovered that week. You've given it on to others. Interesting to hear. Anything about your experience of going through that care as a patient? Did you change or alter anything about the care that you give or did it instead maybe validate to yourself "Okay, you know what I'm doing this okay. I'm giving exactly the type of care that I would expect to have gotten myself." Was there anything that you learned by going through it, that altered the way you approach patients?

Dr. Merajver:  Yes. All of medicine in a way are conversations that we have with our patients and their family. Right? We practice medicine through conversations. People think that we practice medicine with the electronic medical records. Forget that. That's just an accent of history.

What we do is, use our brain to help people. It's what medicine is all about. And to conversations ... to pro's and con's and to reasoning things and to helping people find their path.

What my experience gave me and I've always taken pride as a physician in thinking when I'm not in front of a patient. When I'm by myself thinking of a life and what I do, I like to think of ways to say things to people.

What words should I use, and I have trained myself to use certain words or certain comparisons to explain cancer and cancer therapy to people. In general, in the community and when I teach to my students ... when I teach at the website and then to my patients when I treat them.

What it did for me, is it added to my vocabulary. When I experienced bilateral mastectomies as a patient, it incredibly added to my vocabulary. When I describe bilateral mastectomies to my patients and I do that very often.

A lot of my patients undergo bilateral mastectomies. Now that I have been a patient in that situation, I do have different words, different things I say. When I treat them with a drugs I'm taking, then I'm able to say other things.

Some patients, they're close enough and I've known them long enough. But they know that I don't necessarily bring up. They don't know why I'm describing things in great detail. Some of them know but most of them don't.

But I feel that it does help me get closer in those parts of the treatment that I have experienced.

Chris Riback:  Dr. Merajver just to close out and what an interesting point about vocabulary and conversation and change-

Dr. Merajver:  ... It's so important-

Chris Riback:  Yes -

Dr. Merajver:  ... So important.

Chris Riback:  Yes -

Dr. Merajver:  ... What you say can not be unsaid. To think about the words is super important I think.

Chris Riback:  To close out this conversation and words that I could keep listening to from you for a very long time. It's a terrific and the way that you approach everything, just all comes together. You can really feel it. You've touched on this already. The BCRF and the role that they've played in your research. How would you characterize that?

Dr. Merajver:  Well, life's changing. I would still be doing research if I didn't have a BCRF funding but all of the great breakthroughs that I've hoped for in my career, were accelerated and in some cases, completely made possible. It sounds so tremendously.

My contributions to humanity which is the whole point of the work I do. I don't know what else to say, but to say it's transformational. A transformation I respect because not just the dollars. The dollars are certainly an important part of it. For the listeners out there, the funding is unbelievably important.

But the other part is the collaborations. It's the whole group of scientists from around the world thinking in different ways and comparing ideas. It's just an amazing community and I have learned so much from them.

Chris Riback:  Around the world really matters to you doesn't it.

Dr. Merajver:  Oh for sure.

Chris Riback:  Very quickly, you're doing remarkable work not just in the United States, but truly all over the world including Africa.

Yes, we are definitely very interested in continuing our work in Africa and we are studying African samples in our lab, and we have trained African Researchers in our lab, who are practicing in different countries. I am very committed to global cancer cells and I will continue to do the best I can.

I think we need to enhance, take care of women around the world and there are not a lot of us in the United States working on this and if we continue, it's difficult with the funding. It's expensive. Things cost a lot more if you have to spend twenty thousand dollars traveling back and forth, and sending samples and buying equipment in another country and things like that.

But we manage to make at least some progress. So, yes we are here to create cures for everyone.

Chris Riback:  Dr. Merajver, thank you. Thank you for your time and of course, most importantly for the work and care that you've given to people all over the world.

Dr. Merajver:  My pleasure. I always end my conversations with my patients: “To life!”

Chris Riback:  “To life!” Thank you.

Chris Riback:  That was my conversation with Dr. Merajver. My thanks to Dr. Merajver for joining and you for listening. To learn more about breast cancer research or to subscribe to our podcast, to bcrf.org/podcasts.

Investigating Breast Cancer: Dr. Joseph Sparano

 

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It was among the biggest cancer news stories of the year: A new study – the largest breast cancer treatment trial ever conducted – showed no benefit from chemotherapy for 70 percent of women with the most common type of breast cancer. As the Washington Post described, that means: “most patients who have an intermediate risk of a cancer recurrence — a group that numbers 65,000 women a year in the United States — can avoid chemotherapy and its often debilitating side effects.”

The TAILORx trial, as it is known, is helping change everyday procedures in the everyday lives of patients around the world. And the lead author is our guest today.

Dr. Joseph Sparano is Professor at Albert Einstein College of Medicine. He is Vice-Chair, ECOG-ACRIN Cancer Research Group and has been a BCRF Investigator since 2012.


Read the transcript of the conversation below:

Chris Riback: I’m Chris Riback. This is Investigating Breast Cancer, the podcast of the Breast Cancer Research Foundation and conversations with the world’s leading scientists studying breast cancer prevention, diagnosis, treatment, survivorship and metastasis.

It was among the biggest cancer news stories of the year: a new study – the largest breast cancer treatment trial ever conducted – showed no benefit from chemotherapy for 70 percent of women with the most common type of breast cancer. As the Washington Post described, that means: “most patients who have an intermediate risk of a cancer recurrence — a group that numbers 65,000 women a year in the United States — can avoid chemotherapy and its often debilitating side effects.”

The TAILORx trial, as it is known, is helping change everyday procedures in the everyday lives of patients around the world. And the lead author is our guest today.

Dr. Joseph Sparano is Professor at Albert Einstein College of Medicine. He is Vice-Chair, ECOG-ACRIN Cancer Research Group and has been a BCRF Investigator since 2012.

I asked Dr. Sparano about the TAILORx study and how it feels to have been part of such landmark work. But I also asked Dr. Sparano about what’s next – about new work he’s doing around breast cancer recurrence – specifically relapses that occur many years after original diagnosis. 

Chris Riback: Dr. Sparano, thanks for joining me, I appreciate your time.

Dr. Joseph Sparano:  My pleasure. Thank you for the invitation.

Chris Riback: So you've had quite a last six months, to say the least. Any big news or studies that maybe you've been associated with that you'd like to discuss? Anything in the New York Times for example?

Dr. Joseph Sparano: Sure. I guess my mention in the Times has been for good reasons and that surrounded the release of the results of the long awaited TAILORx Trial and this was really the first precision medicine trial and the largest precision medicine trial that's ever been coordinated and supported by the National Cancer Institute, probably will be the largest one ever conducted. Where we screened about 10,000 women who had estrogen receptor-positive, HER-2 negative lymph node-negative breast cancer which accounts for about half of all breast cancers in the US and about 9% of all cancers in the US.

Dr. Joseph Sparano: A cancer where we typically recommend chemotherapy, adjuvant chemotherapy after potentially curative surgery to help reduce the risk of recurrence. But on average only about 3% to 5% of patients treated actually derived benefit. And our approach for the last probably 20 or so years has been to treat patients as a precaution in order to prevent the possibility of recurrence even though we really couldn't identify who was more or less likely to have benefit from therapy.

So what we did was we took a new diagnostic test that became available around 2004, 2005 called the Oncotype DX 21-gene recurrent score. It's a test that could be done on routinely processed and collected tumor tissue that's typically stored in the pathology lab after it's removed and where it's sent to a lab and the RNA is extracted from the tumor in a panel of 21 genes evaluated. It's computed into what's called a recurrence score that provides prognostic information, it provides information that identifies who's at greater or lesser risk of occurrence if treated with endocrine therapy alone.

But also more importantly, it identifies about 15% to 20% of patients who are the ones who are deriving the benefit from chemotherapy and it sort of takes the guesswork out of identifying and selecting the patients who are most likely to benefit. So what we did in TAILORx was we took patients who had, as I said, ER positive, HER-2 negative breast cancer who met standard clinical criteria for recommending or at least considering chemotherapy and then we assigned their chemotherapy treatment based on the score so that the score was low, very low.

Dr. Joseph Sparano: We advised only endocrine therapy alone because we knew those patients had a very good prognosis for the endocrine therapy alone they were unlikely to benefit from chemo. And for the patients who score was very high we recommended chemotherapy and endocrine therapy for those patients because we know those patients had a 3% to 4% benefit, more like a 25% benefit from chemo. And for the remaining two thirds of patients who score was in the mid range, we randomize those patients by chance to receive chemo endocrine therapy which we consider the standard arm versus endocrine therapy alone.

Dr. Joseph Sparano: And what we found is that the two-thirds of patients who fell into this group who had a mid range score, who had a risk of recurrence that was high enough to consider chemotherapy that we found that they actually were not benefiting from chemotherapy and that was a major finding that we reported at the 2018 ESCO meeting and published in the New England Journal of Medicine. So the bottom line is that it's turned this test which previously provided a clear direction to only about a third of patients who had a very high or very low score into a binary test. The test I can tell you, yes, you benefit from chemotherapy, you're in the 15%, maybe 20% who benefit from chemotherapy or know you're in the 80% to 85% of patients who definitely don't benefit from chemotherapy.

Chris Riback: It's just remarkable. I mean, it's difficult to overstate, I would think, how massive of a change that is and kind of more specifically how big of a change that is not just, of course in the approach and the care for patients, of course, we can talk about that, but also the very practical and immediate effect that that has on people's lives on not other the folks who otherwise would have been undergoing chemotherapy. And now because of this, because I guess previously everyone, as you said, as a preventative measure, everyone was kind of assigned chemotherapy and now that's no longer the case and just to be part of something that's just such a massive change in immediate life enjoyment, life style, that's just got to feel remarkable.

Dr. Joseph Sparano: It does, and it's a very gratifying experience. I'm particularly thankful to the 10,273 woman who volunteered for the study because none of this would have been possible without them. And I think many of them actually who participated who were in the mid range group, at least half of those women benefited because they would have otherwise received chemotherapy and they didn't. We found out now that they did just as well. So there are actually a large number of those patients directly benefited from participating the trial number one.

Number two, they move the field forward and of now by virtue of the trial we now have a higher level of evidence to make treatment recommendations with a greater degree of precision than we've ever had. And thirdly, they've pushed the field even forward beyond the clinical scenario that the trial was designed for that is no negative disease because now people have a much higher comfort level with the using this test and maybe even other tests to spare the use of chemotherapy and women who were at higher risk of recurrence because of positive axillary lymph nodes.

And in fact, at the recent San Antonio breast cancer symposium there was an entire session that was devoted to this, there was a counterpoint type of debate between two prominent breast medical oncologists about what they would do in patients with no positive disease on the basis of information regarding not only the clinical pathologic features but also the information provided by the recurrent score test to 21-gene. So it's moved the field I think forward and it's happening at a good time because we actually now have other treatments available that may help prevent recurrence that are not chemotherapy.

Dr. Joseph Sparano: We've completed very large trials testing those agents, at least one very large trial called the Palace Trial, which is testing one of those agents called Power The Cycle of an early stage breast cancer and we have other new drugs that we're now able to move into this space and test determine whether or not they can help reduce the risk of recurrence in a way that chemotherapy has not been able to do.

Chris Riback: Silly question. You said it was common practice commonly understood and I believe, please correct me if I'm wrong, it was around 2000 that the guidance came out for preventative measure to use chemotherapy. Do I have that date right? Around 2000?

Dr. Joseph Sparano: Yes, there was an expert panel convened by the National Institute of Health that recommended that all women, regardless of lymph nodes status, hormonal status or age be considered for adjuvant chemotherapy.

Chris Riback: So you've got an NIH sponsored group and that comes out with that type of finding, very very strong finding. What made you or others and the folks that you work with think, wait a second, maybe we ought to do a study and not just to study but you know, the biggest of all time and really look at that and question whether that recommendation is what we actually should be recommending? What was your hypothesis? What kind of drove you towards this?

Dr. Joseph Sparano: Well, first of all, we knew at the time that probably 60% or more of patients who fell into this category were receiving adjuvant chemotherapy. Why wasn't a larger proportion of patients receiving? Well, probably because women who were older than 70 or who had significant medical problems or patients who just declining therapy because of the uncertainty of its potential benefit. So even with those patients who were not receiving therapy for whatever reason there was still a very large portion of patients who fell in this group of receiving chemotherapy, possibly up to 80,000 women a year.

So that was point number one. Point number two was we never really had the tools to be able to evaluate gene expression profiling or other types of molecular profiling and breast cancer and those tools allowed us to develop assays that could do that. And then thirdly, we actually had the results of studies that showed that this assay, this test was not only prognostic but it was predictive of benefit from chemotherapy if the score was above a certain level. And we haven't information based not on the results of prospective clinical trials that were designed to test that, because those trials take years to do.

What we had was we had tumor tissue stored from trials that had been completed years ago where we have long term follow up in which patients are randomized to chemotherapy or not and we were able to go back and study those samples and prospectively apply this new test. And when we did that, we were able to determine in a relatively short period of time that the test provided not only prognostic information but also predictive information for chemotherapy benefit. But then we were stuck with the fact that yes, the test provided useful information for maybe up to 30 patients who had a very high or very low score.

But we really weren't sure about the majority of patients who had a score that was in the mid range. That was a key. And I guess the other important point is, when these tests are developed they're sort of developed in a way that we study the entire study population, the entire cohort of patients who were on that clinical trial, but that's not how clinicians use the test in practice. So they will selectively use the test. So for example, for patient who has a larger tumor maybe more than a three centimeter tumor and someone who's younger maybe under the age of 50 was a high grade despite being estrogen and progesterone receptor positive that clinician may not order that test.

Or if someone is older and has a tumor that's less than a centimeter low grade, that clinician may not order the test. They make a clinical decision without that. The test is ordered mainly in situations where the clinician is uncertain where they have a woman who is in maybe the early 50s, who has a tumor between one and two centimeters and intermediate grade. And this was the most common scenario, this was the most common clinical scenario in TAILORx and is one of the most common clinical scenarios in clinical practice. And this is the population of patients from whom we have a very clear and convincing answer that the trial addressed.

Chris Riback: Did you work in translational medicine you're talking about a little bit I guess in terms of the actual tests that are being ordered for patients. But that aspect of connecting research and actual medical practice with patients. First of all, I just want to confirm that I have that right that you do both and then if so what role did that play and if you don't practice translational medicine, what role did feedback from the field, from patients play in how you approached the research?

Dr. Joseph Sparano: Yes translational medicine is defined as translating information, techniques, technology from the laboratory to the clinic and certainly the development of the 21-gene recurrence score leveraged technological advances that allowed one to extract RNA from routinely processed formal and fixed paraffin embedded tumor tissue. So that was really a huge technological advancement. The other advancement was the discovery based research that identified the genes that were associated with recurrence through what's called supervised analyses.

Meaning that the researchers tested the association of specific patterns of gene expression with a recurrence versus no recurrence and looked at the differences in gene expression between the two and then developed an algorithm that integrated the information from these multiple genes. So yes, that's an example of the translational research. In terms of the input of patients and advocates that was very important. In the design of the trial there were patient advocates involved in the ECOG-ACRIN research group and other groups. One in particular Mary Lou Smith lead an effort to solicit feedback from patient advocates regarding the trial, it's design, the question it was addressing.

The methods by which it was trying to address it. And in addition she organized and solicited feedback from patients, ordinary patients who are not professional advocates. And that feedback was really very important in not only helping to design the trial and affirming what our design was, but it also helps in terms of developing patient education materials that can help explain to patients why we were doing the trial and why it was important to them to volunteer for it.

Chris Riback: Yeah, the feedback and the communication back and forth between research and actual work with actual patients that occurs in a clinic is always interesting to me and I can't tell you the number of researchers that I've spoken with who just highlight that component as important in terms of their understanding what they learn along the way, seeing it and getting that immediate human patient level feedback. It never ceases to amaze are impressed me how important that is. I want to ask you about another objective to the study which was to create a bio repository of tissue and blood, and you've mentioned this a bit, so that researchers can learn more about the patients in the low risk groups who had a recurrence and in the high risk groups who recurred despite added chemotherapy. And in fact, you've ended up with quite a repository, haven't you?

Dr. Joseph Sparano: Yes, we have and actually this is where the funding from the BCRF was critical in terms of providing additional resources that needed to establish this bio repository. And it's been money well spent because of the fact that we have a really long term follow up on a very large number of patients who are uniformly treated and we have plans to do more advanced molecular sequencing on selected tumor specimens from patients, including patients who relapsed and those who didn't relapse so that we can get to another level of information that may not be provided by the recurrence score that may provide further insights with regard to prognosis, prediction and also identifying potential therapeutic targets. In other words, identifying non chemotherapy approaches that might help reduce the risk of recurrence or even treat patients with more advanced disease. So that that work is currently in process.

Chris Riback: Question about you. How did you kind of get started in all of this in the first place? I mean, going way back and growing up, was it always science and math for you? Did you think about ever becoming a playwright or poet or anything like that, or were you always math and science?

Dr. Joseph Sparano: I was pretty much math and science with sort of a touch of humanity and in terms of the fact that I was influenced very early on by a family member, my maternal grandmother who lived with us in a typical first second generation Italian-American home who developed breast cancer when I was very young and died of the disease. My recollection of the events although I was very young is that she had neglected breast cancer and presented with a very locally advanced stage of disease. And I do have the vivid memories of the priests coming into our home and giving last rites in a couple of occasions and her dealing with her illness.

So that sort of sparked my interest in medicine and in general and in breast cancer in particular. And what also interested me in oncology was a second aspect of it was kind of the mystery behind it. That at the time that I got into the field or certainly when I was growing up and learning about science and medicine, a lot of it was very very mysterious. We had very little insight into what caused cancer, what drove cancer or even how to treat cancer. So that was the second critical point that that drew me to this field. And the third critical point was that for many types of human illnesses you can treat it, you can manage it, but you can't necessarily cure it, such as hypertension or diabetes or heart disease.

But cancer is actually a disease that in many forms of cancer you can cure with either a combination of local therapy like surgery, radiation, and sometimes with systemic therapies added or entirely with systemic therapy with certain blood disorders, blood cancers, for example. So those are the three things that kind of drew me to it. The stakes associated with a diagnosis and the human toll it can take the mystery that surrounded a lot of it and the challenge in sort of uncovering those mysteries and deciphering how to better treat cancer and then the opportunity to actually cure people of an illness that's potentially life threatening.

Chris Riback: How old were you when you were experiencing that with your grandmother?

Dr. Joseph Sparano: I was about the age of five but it left a very big impression on me, let's say. But I also was sort of gravitated and inclined and interested in science. Again, what intrigued me about science was the mystery of a lot of science back then, especially the life sciences.

Chris Riback: That's a remarkable mix of the personal but also I guess it just sounds like part of your DNA where you were just talking about the curiosity, about the life sciences and the mystery, very interesting and always interesting how different aspects of one's own personality and external events frequently can come together to set a live course. So the last item that I kind of have for you and what I think most of us, many of us, maybe all of us could really learn from you is time management. So I did a quick review of your work and you're involved and have been involved in so many different types of major research and major efforts.

I mean biomarkers of recurrence in early stage breast cancer, improving treatment outcomes in breast cancer, developing invalidating gene expression signatures in breast cancer, evaluating interaction between breast cancer and the micro environment. There are others including developing more effective therapies for HIV associated cancers. So first, how do you find all the time, and secondly, do these all connect in some way that is easily understood by the rest of us?

Dr. Joseph Sparano: Well, I guess the point of connection is the fact that at the end of the day or the beginning of the day, or between the beginning of the end of the day, for the most part I'm a clinician who tweets patients and most of the work that I do or really all of the work that I do I'm motivated and become interested involved with because it directly impacts the care of the patients that I care for. And so that really sort of guides me or directs me to become interested in certain areas. The second important point is that I certainly don't do this work alone, I surround myself with and interact with many, many, many talented people and I try and learn as much as I can from them and also look for opportunities to apply what I think is the best work to the care of my patients.

And then thirdly, some of the eclectic nature of the work that I'm involved with such as the HIV associated cancers dates back to things that I was interested in because I commonly saw them in practice in the 1990s in the institution that I practice in and in the area of New York City that I practice in, HIV associated cancers were very common and rapidly lethal. And the prognosis associated with them has improved very much in part because of improved therapies directed against HIV but also improved anti cancer therapies. So that's sort of I think may explain some of the eclectic nature of some of the stuff that I've been involved with.

Chris Riback: And Dr. Sparano there's work that you are currently doing funded by BCRF, tell me about that.

Dr. Joseph Sparano: Yeah this is really important work that I'm really excited about. It actually started about five years ago when it became more and more recognized that half of all recurrences have estrogen receptor positive HER-2 negative breast cancer, the most common breast cancer subtype occurs not within the first five years of diagnosis but after five years. And this is a major problem and I became more aware of it as I became a more experienced clinician and had patients in my practice for long periods of time. And seeing women have a recurrence of their disease, 5, 10, 15, 20 and even 30 years after their diagnosis.

And we really had no clue as to why these women were relapsing this late and what we can do to prevent these relapses. So I saw an opportunity to study this by evaluating women and offering women the opportunity to donate blood specimens who a woman who had already participated in other clinical trials were different treatments were tested and asked them would they participate another clinical trial because we were following them anyway, we knew what treatment they had, we already had their tumor specimens and their blood specimens at the time of their diagnosis and we asked them to provide additional blood specimens.

And we created what we call the lake relapse bio specimen bank. So right now we have over, it may be close to 20,000 blood specimens in that bank so that we can study and apply some of the newest technologies like the ability to detect to our DNA in the blood. The ability to detect circulating tumor cells in the blood so we can evaluate tumor associated factors associated with recurrence and also host associated factors because we do know that there are factors in the patient that may be assisting and driving the risk of recurrence.

So one of the first results that we had from that effort was a study where we looked for the presence of circulating tumor cells in women who were between four and a half and seven and a half years after diagnosis, clinically cancer free no evidence of recurrence by history and physical. And we found that about 5% of those women who had estrogen receptor positive, HER-2 negative disease actually had tumor cells circulating in their blood and we found that those women who had detectable, what we call seats and fees had about a 13 fold higher risk of occurrence.

And that for the 5% of those who are CTC positive they had about a 30% risk of having a recurrence by two years whereas they were CTC negative they had a 97% chance of being cancer free at two years. So what we're doing now is we're in the process of designing a very large trial, a TAILORx like trial really where we will evaluate women who are five or more years after diagnosis, perform a CTC type test on them and then to select those women and then test a newer treatment like a CDK 4/6 inhibitor to see if we can prevent a recurrence from ever happening. The timing is actually right for this because the FDA has recently now recognized what's called metastasis free survival as an end point that can support the approval of drugs for the syndication.

And the FDA just approved two drugs in men with prostate cancer in a very similar situation. Men who had local treatment for prostate cancer, local treatment meaning either surgery and or radiation who have a rising PSA but who have no evidence of cancer recurrence by standard imaging, CAT scans or bone scans. There have been two randomized trial showing that men who were treated with anti angiogenic therapy that can prevent the development of recurrence. So we think we can apply the same model in breast cancer and the NCI will be hosting a meeting in the Spring of 2019 to discuss and plan a trial that will have this as the foundation, that will have this as a framework for trying to prevent late recurrence.

So I think this is the next frontier of trying to prevent recurrence of breast cancer. And the future that I see is that we'll be able to use these more sophisticated markers to detect what's called minimal residual disease, MRD, and identify who's really at risk of recurrence and then tailor treatments to prevent that risk. Because right now there's really no surveillance that's recommended in this setting. Conventional blood tests or tumor markers are not recommended scans, they're not recommended and we need better ways to monitor people who are at the highest risk of recurrence and intervene before that recurrence actually occurs.

Chris Riback: And I assume this will help identify which patients are most likely to benefit then from specific therapies, is that right?

Dr. Joseph Sparano: That's the hope. For example, there are tests for circulating tumor DNA that can detect mutations and what's called the ESR-1 or the estrogen receptor gene and those mutations identify tumors that are more sensitive to specific drugs. So yes, some of the technology that's evolving will allow us to identify not only who's at high risk but what drugs they may be more or less likely to respond to.

Chris Riback: Dr. Sparano, thank you. Thank you for the conversation and thank you for work that you do.

Dr. Joseph Sparano: Thank you. It's been my pleasure speaking with you.

Chris Riback: That was my conversation with Dr. Joseph Sparano. My thanks to Dr. Sparano for joining and you for listening. To learn more about breast cancer research or to subscribe to our podcast, go to bcrf.org/podcasts.

BCRF Announces New Board Member

 

The Breast Cancer Research Foundation (BCRF) is proud to announce the appointment of Karen Hale to the Foundation’s esteemed Board of Directors, which is co-chaired by William P. Lauder and Kinga Lampert.

“It’s an honor to join BCRF’s Board of Directors. I love what BCRF stands for: research. Collaborative research will be the answer to our many questions about breast cancer and all cancers,” said Karen Hale.

Karen and her husband, Rob, are Boston-based philanthropists who have been passionate supporters of BCRF for seven years. Their commitment to funding transformative cancer research stems from personal experiences with the disease. Karen’s mother is a breast cancer survivor, and Rob lost his father to pancreatic cancer.

In 2016, the Hales were honored with the Inaugural Carolyn Lynch Humanitarian Award at BCRF’s Boston Hot Pink Party, celebrating their dedication to impact-driven philanthropy, especially in furthering medical research.

Karen has a keen interest in advancing cancer research, and her recent appointment to BCRF’s Board of Directors is a natural fit. Together with Rob, Karen is deeply involved in numerous Boston-based institutions including Boston Children’s Hospital, Brigham and Women’s Hospital, and the Dana-Farber Cancer Institute.

New England-based investigators make up the second highest concentration of BCRF funding. In 2018, more than $8 million in grants was awarded to 40 investigators in the region, bringing BCRF’s cumulative investment in New England to over $81 million. As an active member of the Boston community, this holds special meaning for Karen.   

“I continue to be impressed by the scope of BCRF, a small but mighty organization,” said Hale. “The research we fund year after year touches the lives of so many. I look forward to being a part of the continued progress, lives saved, and good work we will do together.”

BCRF Investigators Honored at the 2018 San Antonio Breast Cancer Symposium

 

The San Antonio Breast Cancer Symposium is the largest annual meeting dedicated to breast cancer research. Each year SABCS attracts thousands of experts from around in the world in clinical oncology, basic, and translational research, as well as representatives from industry, government and patient advocacy.

It is a unique opportunity for members of the clinical and research community to hear the latest in the field and to acknowledge the accomplishments and contributions of colleagues. This year, three BCRF researchers were honored with landmark awards.

Dr. Ian Smith: 2018 recipient of the William L. McGuire Memorial Lecture.

Named in honor of one of the co-founders of the San Antonio conference, this award lecture recognizes an investigator whose career achievements have made an impact on our understanding of the pathogenesis and/or outcome of patients with breast cancer.

Dr. Smith was selected as the 2018 recipient for his lifetime achievements that changed the management of breast cancer, including his pioneering work in developing and testing aromatase inhibitors and in advancing the use neoadjuvant (pre-surgical) therapy.

In his award lecture, Dr. Smith discussed how biomarkers in the primary tumor can be used to inform appropriate therapy for patients, including reducing the need for surgery. Using a marker called Ki67, Dr. Smith and his BCRF colleague Dr. Mitch Dowsett have shown that reduction in Ki67 after neoadjuvant therapy may be a sign of better prognosis for some patients.

Dr. Smith joins twelve BCRF investigators as past recipients of this prestigious award. You can read more about the BCRF research of Drs. Smith and Dowsett here.  

Dr. Eric Winer: 2018 Recipient of the Brinker Award for Scientific Distinction in Clinical Research.

Dr. Winer was selected for this award in recognition of his devotion to applying advanced from clinical trials into daily practice to improve patient care and quality of life. His award lecture focused on the subject of treatment de-escalation. He touched on how over-diagnosis leads to over treatment of some women whose screen-detected cancer did not pose a threat, and the need to identify individuals who need more treatment versus those who need less. He ended his talk emphasizing the potential of pre-surgical (neoadjuvant) therapy in identifying patients who will benefit from less–rather than more– therapy.

Dr. Winer acknowledged that de-escalation of therapy comes with challenges for both patients, who fear a recurrence and for doctors, who want to give their patients the best care. Dr. Winer joins 25 BCRF investigators to receive a Brinker Award since the award was established in 1992.

You can read more about Dr. Winer’s BCRF research here.

Dr. Ann Partridge: 2018 Recipient of the AACR Outstanding Investigator Award in Breast Cancer Research.

This award recognizes an investigator of no more than 50 years of age whose novel and significant work has had or may have a far-reaching impact on the etiology, detection, diagnosis, treatment, or prevention of breast cancer. Dr. Ann Partridge was selected for the 2018 award for the significant impact her work has had on the clinical epidemiology of breast cancer in young women, and her seminal work focused on understanding and improving their care and outcomes.

During her talk, Dr. Partridge emphasized some of the disparities in diagnosis and outcomes in young women (under 40 year of age), including the greater incidence of triple negative breast cancer and HER2-positive breast cancers in younger women compared to older women. Even when younger women are diagnosed with low risk breast cancer, they tend to have a worse outcome than older women. Listen to BCRF’s Facebook Live interview with Dr. Partridge below.

Past recipients of the AACR Outstanding Investigator Award in Breast Cancer Research include the following BCRF investigators: Dr. Fergus Couch, 2016; Dr. Yibin Kang, 2014; Dr. Kornelia Polyak, 2012; Dr. Charles Perou, 2009.

Play for P.I.N.K. Donates $4.75 Million to BCRF

 

Play for P.I.N.K. (PFP) is the single largest independent donor to BCRF. The organization empowers 30,000 volunteers from across the country to host hundreds of lifestyle and sporting events to advance breast cancer research.

This past year, PFP donated $4.75 million to BCRF bringing their cumulative total to $57.5 million since the organization was founded over 20 years ago. 

“We continue to be amazed by the outstanding dedication of our community,” said Play for P.I.N.K. President and Founder Laura Lassman. “Raising significant funds for research is critical to ensure more breakthroughs are made.”

Laura Lassman started Play for P.I.N.K. as a one-time golf tournament in New Jersey to fund breast cancer research. The idea was inspired by her close friend who was diagnosed with breast cancer. Laura rallied her local country club to raise funds – and her community was tremendously supportive.

When Laura was introduced to BCRF Founder Evelyn H. Lauder, the organization named BCRF as their sole beneficiary.  Thanks to its Title Sponsor, The Estée Lauder Companies’ Breast Cancer Campaign, Play for P.I.N.K. donates 100% of its proceeds directly to the Foundation.

“We’re astounded by Play for P.I.N.K.’s continued support which is critical to BCRF’s grant-making capability,” said BCRF President Myra Biblowit. “We’re extremely proud of our partnership and indebted to everyone involved for their incredible work.”

Thanks to this devoted community comprised of best friends, country clubs and school groups, progress has been made in breast cancer research.

The organization currently supports 26 researchers, which will grow in the coming year thanks to their recent donation. Scientific advances made possible in part by PFP brings us closer to a world filled with improved outcomes and saved lives.

“If not for BCRF/PFP support, we would not have been able to obtain NCI-funding for the WHI Cancer Survivor Cohort, a unique resource for studying recurrence and late effects of treatment,” said PFP-supported researcher Dr. Electra Paskett. “This is a benefit for all breast cancer survivors.”

To learn how you can start a Play for P.I.N.K., visit  www.playforpink.org

5 Key Highlights from the 2018 San Antonio Breast Cancer Symposium

 

Last month BCRF attended the 41st Annual San Antonio Breast Cancer Symposium (SABCS), the largest annual breast cancer meeting in the world. This year’s meeting hosted more than 7,500 attendees from 90 countries. The event presented a balance of clinical, basic and translational research in breast cancer and was the first national meeting to include programs for patient advocates.

Each year, BCRF staff attends SABCS to catch on the latest breast cancer research, connect with BCRF researchers and to represent BCRF at nightly advocacy events.

Below are highlights from the meeting.

T-DM 1 improves disease-free survival compared to trastuzumab in patients with early-stage HER2-positive breast cancer.

In a report from the Katherine study, researchers demonstrated that the antibody-drug conjugate, T-DM 1 (Kadcyla®) was better than trastuzumab (Herceptin®) in reducing the risk of recurrence of invasive breast cancer in patients with early-stage HER2-positive breast cancer.

HER2-positive breast cancer accounts for approximately 20 percent of breast cancers. Neoadjuvant (pre-surgical) therapy of trastuzumab plus chemotherapy is typically prescribed for patients with operable (non-metastatic) disease. Not all patients, however, respond to the neoadjuvant therapy indicating a greater risk of recurrence after surgery. The Katherine study enrolled patients who fell into this category. After surgery patients were randomized to continue trastuzumab or T-DM 1.

While it is too early to determine the more effective therapy in improving overall survival, the primary analysis of breast cancer recurrence showed that patients receiving T-DM 1 were 50 percent less likely to have a recurrence than those receiving trastuzumab.

Using neoadjuvant therapy to inform prognosis and treatment options.

Pre-surgical therapy – called neoadjuvant therapy–was initially used to reduce tumor burden in patients with locally advanced breast cancer. The goal was to reduce the amount of surgery required, in many cases downgrading surgery from mastectomy to breast conserving surgery or lumpectomy. Years of clinical studies, however, have suggested that the level of response to neoadjuvant therapy may also predict risk of recurrence in patients with early-stage breast cancer. 

Pathological complete response (pCR) – a condition that refers to there being no detectable invasive tumor in the breast or lymph nodes – is the measure used to predict recurrence after neoadjuvant therapy. In a multi-study analysis reported at SABCS, pCR was associated with a significant decrease in risk of recurrence, particularly among patients with early-stage triple negative breast cancer. The study authors noted that pCR may inform subsequent treatment, resulting in de-escalation of therapy for those with low risk of recurrence and likewise, the use of more aggressive therapy in those who do not achieve pCR following neoadjuvant therapy.

Low-dose tamoxifen in pre-invasive breast cancer reduces the risk of invasive breast cancer. 

Pre-invasive breast lesions including atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS) and lobular carcinoma in situ (LCIS) make up about 20 percent of all breast neoplasms (abnormal growths). In cases where these neoplasms are dependent on the hormone estrogen (ER-positive), therapy often includes surgery followed by anti-estrogen therapy such as tamoxifen. The side effects of anti-estrogen therapy can make it difficult for patients to complete the therapy and potentially increase their risk of invasive breast cancer.

A study conducted across 14 sites in Italy randomized 500 women with ADH, DCIS or LCIS to receive a low dose of tamoxifen (5-mg dose vs. 20-mg dose) or placebo for three years. After five years of follow up, the investigators reported that the low-dose tamoxifen reduced the risk of recurrence by 50 percent compared to placebo.  The authors noted that while there were considerably fewer adverse effects with the lower dose of tamoxifen compared to the usual dose, less than 65 percent of patients completed the full regimen.

Follow up from TAILORx reveals racial disparity in breast cancer outcomes.

A sub analysis of the TAILORx study of women with early-stage, estrogen receptor- positive, HER2-negative breast cancer showed that black women had a worse breast cancer outcome than white women despite similar Oncotype DX scores and similar therapies.

The study, presented by BCRF investigator Kathy Albain, included 9,719 patients (8,189 white, 693 black, 405 Asian, and 432 of unknown race) The researchers found that black women were 39 percent more likely to have a recurrence and 52 percent more likely to die from their disease than white women. These differences could not be accounted for in different recurrence scores, treatments or tumor pathology.

“Our results suggest that biologic differences may contribute to the significantly different outcomes of black women compared to others with breast cancer,” Dr. Albain said.

For more information on the groundbreaking TAILORx trial see our previous blog.

Biomarker predicts response to immunotherapy in patients with advance triple negative breast cancer.

The IMpassion 130 trial, published in October 2018, was the first trial to show benefits of immunotherapy for triple negative breast cancer (TNBC). In a follow up analysis, study author and BCRF investigator Leisha Emens reported that the immune marker, PD-L1, was effective at identifying those patients most likely to respond the PD-L1 targeted therapy, atezolizumab.

Newly diagnosed patients with metastatic TNBC received chemotherapy plus atezolizumab or plus a placebo. In the interim analysis reported at SABCS, patients with PD-L1-positive tumors who receive the atezolizumab/chemotherapy regimen had an overall survival of 25 months vs. 15.5 months in those with receiving chemotherapy/placebo. There was little difference in survival benefit of the two therapies in patients whose tumors did not have the PD-L1 marker.

To learn more about this new finding, tune in to our Facebook Live interview with Dr. Emens.

Tackle Your New Year’s Resolutions while Supporting Research

 

From office supplies to products that encourage a healthy lifestyle, BCRF’s Corporate Partners make it easy to achieve your 2019 goals while advancing lifesaving research. By shopping with our partners, you are helping BCRF researchers find the next breakthrough.

 

Vivora

A revolutionary appropriation of exercise equipment that supplements the use of a traditional office chair, the Vivora Luno Sitting Ball helps makes a difference too. For every purchase, $10 is donated to BCRF.

 

TYR 

A new twist on an old classic, the backpack is packed with state-of-the-art features engineered for athletes on the go. $5 of every purchase supports critical breast cancer research. TYR makes it easy to dive into healthy habits this year!

 

Everlast 

Knockout your 2019 resolutions with Everlast. Everlast donates $75,000 annually to support lifesaving breast cancer research.

 

Day-Timer 

Jot down your to-do list, make note of plans and keep yourself organized each day. Our friends at Day-Timer create a Pink Ribbon collection of planning and organizing products that support BCRF each year, including day-planners, weekly planners, calendars and more. Day-Timer funds 500 hours of research annually!

 

Officemate 

Organize your workspace with Officemate’s complete line of BCRF office supplies including clipboards, staplers, various clips and magnets, scissors, sign holders, and desk accessories. With each purchase of Officemate’s Pink Themed Office Supplies, $0.10-$0.50 per purchase will benefit BCRF.

 

Pentel 

Pentel’s Pink by Pentel line includes quality products that create a fabulous writing experience while supporting breast cancer research. This gel pen is designed with an aluminum alloy barrel for those who want to make a permanent statement and a difference. Pentel will donate $0.05 per purchase, up to $15,000 to BCRF.

 

D’Arrigo 

D’Arrigo CA’s Andy Boy Broccoli Rabe is a powerful superfood that supports critical research. Check out healthy recipes from the D’Arrigo family kitchen that will help you eat well and make an impact this year. Proud partner since 1999, D’Arrigo donates $100,000 annually to support BCRF funded research!

 

K2 

Hitting the slopes this winter? K2 Sports crafts skis, boots, snowboards and ice skates built to create the best experiences. With over $1 million donated to BCRF to-date, K2 Sports makes it easy for winter sports enthusiasts of all abilities to give back while gearing up.

 

ELC Calendar 

Estée Lauder has partnered with fashion and style icon Carine Roitfeld on an exclusive edition of her annual calendar project. This glossy, collectible, limited edition calendar is a tribute to women’s strength and beauty - a gorgeous way to begin 2019. 100% of the purchase price will be donated to fund BCRF research.

Investigating Breast Cancer: Dr. Ben Park

 

Investigating Breast Cancer 1

Subscribe to BCRF Conversations here:

How does cancer grow? Why do some cancers react positively to treatment while others seem to resist? Understanding these relationships, the genetic events and cell-to-cell interactions that lead to cancer, not only can provide better understanding of how cancer develops, but also drive potential new targets for drug development. Understanding these relationships also essential to the incredible work being done by Dr. Ben Ho Park.

Dr. Park was recently appointed as co-leader of the Breast Cancer Research Program, Associate Director for Translational Research, and Director of Precision Oncology at the Vanderbilt-Ingram Cancer Center in Nashville. He's been a BCRF investigator since 2008, and as you'll hear at the top, he also has a unique creative talent that surely won't directly lead to solving breast cancer, but it does to seem to make his lab an engaging and fun place to work. And who knows, perhaps in some way that creative culture is part of what inspires Dr. Park's creative research approaches.


Read the transcript of the conversation below:

Chris Riback: I'm Chris Riback. This is Investigating Breast Cancer, the podcast of the Breast Cancer Research Foundation in conversations with the world's leading scientists studying breast cancer prevention, diagnosis, treatment, survivorship, and metastasis.

How does cancer grow? Why do some cancers react positively to treatment while others seem to resist? Understanding these relationships, the genetic events and cell-to-cell interactions that lead to cancer, not only can provide better understanding of how cancer develops, but also drive potential new targets for drug development. Understanding these relationships also essential to the incredible work being done by Dr. Ben Ho Park.

Dr. Park was recently appointed as co-leader of the Breast Cancer Research Program, Associate Director for Translational Research, and Director of Precision Oncology at the Vanderbilt-Ingram Cancer Center in Nashville. He's been a BCRF investigator since 2008, and as you'll hear at the top, he also has a unique creative talent that surely won't directly lead to solving breast cancer, but it does to seem to make his lab an engaging and fun place to work. And who knows, perhaps in some way that creative culture is part of what inspires Dr. Park's creative research approaches.

Dr. Park, thanks for joining me. I appreciate your time.

Dr. Park: Thank you very much.

Chris Riback: I get to do a lot of these conversations and they're all fascinating, but yours is the first one where I really have to start not with the groundbreaking life-changing research, your life's work, and all of that, but instead, with nicknames. You have some interesting people working in your lab. Apparently I am talking to Dr. Ben "Tally" Ho Park, and among the folks you work with include Sarah "bellum" Croessmann, Mark "of the Covenant" Rosen, and Jenna "if you can, I" Canzoniero. I mean, these are top-notch nicknames, Dr.

Dr. Park: Yeah. I'm quite a fan of puns, and some of those come very easily. Some of them I've actually worked at. Some of them, between you and me, are just really horrible.

Chris Riback: We didn't mention those. They were pretty good.

Dr. Park: I have been known to revise some of them. My favorite one though was I had a graduate student, an MBP student a number of years ago, and her name was Grace Kim. And I called her Grace "for the Cure" Kim. I thought that was perfect.

Chris Riback: Oh, that is really good.

Dr. Park: But I unsuspectingly demand some sort of silly picture. If they don't take it I will just snap one with my iPhone and put it up there and threaten them with that. Most of my trainees are well aware of this.

Chris Riback: Silly photos are quite the threat. But it was fun to read, and I was trying to think through, about the personalities behind it. It gives off a real sense ... I'm sure exactly what the type of place that you run, which is working hard but a bunch of people who have some personality and fun behind them. So, good for you. It must make every day that much more enjoyable.

Dr. Park: I think you know the work hard, play hard philosophy is really strong within our group and our lab. I've always felt like we have to take the mission seriously and the job seriously but we don't have to take ourselves that seriously. And I think that served us well.

Chris Riback: That's well put. Yeah. Anyhow, the serious work is evident, and it's evident in the results. Let's talk about that for a second. Let's turn to the research.

Dr. Park: Sure.

Chris Riback: How does cancer grow?

Dr. Park: Well, you know, it's more of a complicated question than one might actually think. Superficially, we know that cells divide, and cells are the building blocks of our bodies. Each of our bodies have trillions of cells and they're all very tightly controlled, in terms of how they grow and how they don't grow. Those are two equally important parts of the equation.

And so cancer cells can grow because one of those two areas becomes faulty, meaning that cells abnormally can proliferate and/or cells can abnormally not proliferate, meaning that they should stop growing but they don't in cancer, when they really should. And so we think of that in terms of both accelerators and brakes. So you could either press the accelerator and the cells start dividing, or you can disable or have faulty brakes, and in that case the cells will continue to grow when they shouldn't.

But there's even more components to that. Cancer cells not only grow, they spread. That's what we call metastasize. And really, that's what kills patients, is when cancer spreads to distant organs and starts taking over, if you will.

So those fundamental ideas and concepts of how cancer grows, spreads, and kills patients really has dictated our thinking for the better part of 40 years or more. And dictates our thinking in how we're going to attack cancer.

Now we know even more, because what causes the abnormal growth or the abnormal faulty brakes is really a series of genetic events. Each one of our cells has DNA, and DNA is a blueprint of our cells. And what cancer really is are mistakes of DNA. It's almost like our bodies are trying to evolve to be immortal and live forever, but unfortunately they do so at the cost of the host. And so, that kind of process where you have, some folks in our business call it clonal evolution, where you get one mistake that gives it a slight growth advantage and then you get a lot of cells that grow a little bit. You might think of that in terms of like a polyp for colon cancer, but that's not cancer yet. But then any one of those cells can get another genetic hit or mutation as we say. And that gives it another growth advantage, so that now it can become a cancer. And so on and so forth.

So it takes about, people estimate, five to eight of these DNA mistakes or mutations before you can go from a normal cell to a cancer cell.

Chris Riback:  What if one catches such a cell in the first or third mutation? I fully assume that's exactly what one tries to do. We try to catch it before it gets to that five to eight zone?

Dr. Park: Yes, exactly. That's really where the focus is, on earlier prevention and screening. Using again the example of colon cancer, where we have a polyp; a polyp is a growth and it's technically a tumor. A tumor really is just a growth, but it's not necessarily a cancer. And so, if we can screen via colonoscopy and identify a polyp and remove it, then we've really reduced the chance of that polyp ever becoming a cancer.

Similarly, in breast cancer we have the equivalents of things that we call in situ carcinoma, and even earlier, some things that we call ductal hyperplasia. There's also other variants called lobular hyperplasia. But the spectrum of normal to cancer falls along the same paradigm, and many patients in this country will get diagnosed with what we call ductal carcinoma in situ.

Under the microscope, the cells look cancerous, but they haven't actually invaded beyond their normal ductal architecture. The breast tissue is made up largely of ducts and glands, and the cells that form the ducts are the ones that usually become breast cancer in most patients.

So, many patients in this country are diagnosed with stage zero breast cancer. That's a real kind of misnomer and head-scratcher, because how can you have stage zero breast cancer? But that is ductal carcinoma in situ, and it's treated locally as if it were a cancer, because we want to catch it and cure it before it actually does become a cancer.

Chris Riback: Let's focus on what's going on inside and among the cancer cells, because there are some things that you've written that just sound fascinating and confusing for somebody like me, but important no doubt.

So there are these cell-to-cell interactions and you've shown that ... and I'm quoting here ... "cancer cells with single mutations interact with neighboring cells, with other discrete mutations, to increase cancerous growth and drug resistance." But here's the key. These cell-to-cell interactions require physical cell-to-cell contact.

A moment ago you were talking to me about genetic changes, about DNA changes, and about those mutations and then ultimately and potentially, and one hopes not, metastasis. Here, the ways the cells, it sounds like, interact with each other and that the physical cell-to-cell contact is what matters?

Dr. Park: Well, this is a brand new area, and we haven't published this yet, but we are getting ready to submit it for publication. But it is potentially a different way of thinking about how cancer evolves. And this is based upon on observations made by others as well as models that several groups have now shown.

Nobody has really taken human breast cells and demonstrated that there are specific mutations that are distinct in each of those cells but that the cells are otherwise identical, that grown separately have one type of behavior but when you mix them together have another. And that really kind of blows away our concepts of how cancers evolve, as the classic paradigm has always been what I just told you, how you get one genetic hit and then that grows. You get another genetic hit in the same cell ... and we've modeled that as well. You definitely do see changes when you add on mutations within the same cell.

What was recently appreciated was that it looks like in some cancer patients, but not all ... this is again, breast cancer ... that we see different populations of cells or even what we call, sometimes sub-clonal populations of cells, where not all the cells share the same mutations, and some of the cells even have distinct mutations.

And so, it occurred to me that we have really good model systems to try to study this. But it also occurred to me that this is the type of stuff that if you were to try to put this through for traditional funding mechanisms, it would get killed and blown out of the water, because we don't have, at least at the time, we didn't have enough preliminary data to demonstrate that this was something that we could really, at the end of five years, show that we had something. And so, I think the nature of foundations like BCRF that grant these types of programs to investigators, not necessarily to the project, per se, but more about investigators, and we described what we were working on at the time. That really has been essential to our ability to move this project forward.

And so, this is exactly what you were saying. We were very, very surprised to discover this, that if we mix up cells that one of the cells confers a growth advantage to the other cell. And again, that's mind-blowing that you could actually think about that there could be two populations of cells and it's actually the physical touching of those two cells at their outer surface or the membrane, as we call it, that confers this advantage.

We're working on exactly how this happens, and we've got some clues. But this is also an opportunity for thinking about how you would drug these cells. As an example, you might have a drug against one of the mutations, in this particular case, something called PIK3CA versus another drug that hits the HER-2 population. Historically, when we've looked at patients' tumors that have ... let's say 10 percent of the population has the PIK3CA mutation and 90 percent has the HER-2 mutation, we might not think about targeting the PIK3CA, because that's the minority subpopulation. What we're discovering and kind of working out in these models is that thinking may not actually be correct, meaning that you could attack the HER-2 population but that would get rid of everything, but that's the dependent population on the PIK3CA population. So in fact, even though it's 90 percent, it's getting its growth properties from that minor population. And so, it now makes more sense, having that knowledge, we should be attacking that minor subpopulation of cells. And that's again, very, very different than what we would normally do.

Chris Riback: It would be a massive rethinking. It would be a massive rethinking.

Dr. Park: Exactly. And so that's kind of why we were very excited about this, because maybe it affords us an opportunity to think about how cells are dependent upon one another, but you could kind of hit it at the roots, if you will, the thing that's really causing the growth, the population of cells, that is. And that may also be one of the reasons why there's resistance to therapies. It's not really resistance, you're just not getting the right clone or population.

Chris Riback: That's what I was going to ask you was what got your brain thinking in this way? It forces you, or I guess you were forced, to think in a differentiated way, in a way, as you kind of described, that runs counter to decades of thought. Was it something that you saw or was it something that you didn't see, because you just raised drug resistance, which was something I wanted to ask you about. I know that's an area that you-

Dr. Park:  Yep.

Chris Riback:  -have studied. And so, was it more that you saw something or was it that you've looked at drug resistance and thought about drug resistance and you're just like, Man, this doesn't make sense. Why do some therapies work in some cases but not in other cases?

Dr. Park: You know, it's a little of both. It's a combination of having patient data, seeing patients, getting their tumors sequenced, understanding that there are all these subpopulations that sometimes it looks like there's two totally independent tumors, and that's also different in our thinking from traditional standard approaches, or the paradigms that we've been used to working with.

But it's also seeing patients develop drug resistance, and then seeing what's left behind afterwards. So it's really combinations of both that kind of forged our thinking into hypothesizing that maybe there's more to this than what we have really thought, that our models and ideas have been a bit simplistic. In fact, we know that cancer is a very complex disease, that there are many different types and there's many different ways to get to becoming a cancer and becoming metastatic disease.

That's really where I think there's the advantage of having opportunities like BCRF to say, You know what? We know that this could be construed as a crazy idea, that this is not conventional thinking, but you know, this is how discoveries are made.

And you have to do some high-risk high-reward research in one's portfolio if we're really going to dramatically move the needle forward. So I'll be the first to tell you; I don't know whether this is really going to pan out to be a hugely paradigm-shifting way of thinking of all cancers. I actually don't think it's going be for all cancers. But I can tell you, based upon sequencing efforts from breast cancer patients and their individual metastases, we do see this sometimes, and that did inform these experiments.

Chris Riback: Where are you on that? Where are you on that experimentation?

Dr. Park: Well, this is being led by several students in the lab right now. Our hope would be that we can wrap this up in the next few months and submit it for publication somewhere.

But the cool thing about this is that one of the things that my students have done, they've now labeled cells with, we call them fluorescent proteins, so you can actually label the one cell with the one mutation green and the other cell with the other mutation red. We've made these really awesome movies, and I hope that once this is published, I can put them up on the webpage for BCRF, because you can see how the one population, the red cells in this case, if they're not touching any of the green cells, in the middle of the movie, on the screen, they just stay dormant. And then as soon as the green cells are growing and they touch the red cells, the red cells start taking off.

Chris Riback: That would be-

Dr. Park: Yes, pretty cool.

Chris Riback:  -really cool. And also really helpful to communicate the point, because what you just described in a movie in red and green cells and watching them interact or not ... I mean, we can all get that.

So I saw a quote of yours at one point, where you worried potentially that perhaps we are overtreating breast cancer. What did you mean by that and do you have that concern? Was that the right word?

Dr. Park: You got it; you nailed it. But it's not just me. All medical oncologists who treat breast cancer and other types of cancers are worried about this. Not worried in the sense that are we overtreating? Undoubtedly and unequivocally we are overtreating. We worry about the side effects and toxicities.

The paradigm of how we treat early stage breast cancer patients, early stage colorectal cancers, some lung cancers, is that we do surgery ... I mean, for early stage solid tumors, the intent is usually cure. And so, we always say that there's one shot at cure, meaning that first solid tumors, like breast cancer, it's a local problem, meaning that the tumor is in the breast. We need to get rid of that, so we can do that with surgery, and then sometimes surgery with radiation. That can take care of the local component.

But then there's also the systemic component. That is what if cancer cells have now gone into the circulation and what will happen is, with time, if they're left untreated, they will become distant metastatic disease, which is not curable.

And the reason for that is, because as I was telling you before, cancer is really the accumulation of multiple mistakes in the DNA, but it's not a static process. All cancers to some degree have what we call genetic instability, and that's what drives all these mistakes, but it also drives all these subpopulations and what we call tumor heterogeneity. The soonest that we can detect cancer when it's metastasized is about a cubic centimeter, and that's already a billion cancer cells.

Chris Riback:  Wow.

Dr. Park: And each one of those cells is different from each other. We don't have currently drugs that we can throw at patients and cure metastatic disease to get rid of every single cancer cell, because there's so many. There's already drug-resistant clones, if you will, or cells that will grow out to become the new dominant population.

But, if you rewound the clock, before you got to a billion cells, before you can see the cancer metastasized ... let's say it's 10,000 cells ... therein lies the opportunity to try to eradicate microscopic systemic disease that would otherwise come back if left untreated. And that's why we use multiple drugs after surgery, to treat and eradicate patients of microscopic metastatic disease.

So, that all sounds well and good, but here are the real numbers and facts. After surgery or local therapy, so surgery and radiation, the majority of early stage breast cancer patients in this country will be cured. Maybe 60 to 70 percent. And the rest, meaning 30 percent, let's say, are going to have micrometastatic disease. If we treat with chemotherapy, hormone therapy, HER-2 directed therapy, depending upon the type of breast cancer, we can reduce that 30 percent, maybe by half, maybe more, depending upon the subtype. So now, rather than 30 percent of patients recurring with metastatic disease, we've chopped that down to maybe 10 to 15 percent.

Chris Riback: Wow.

Dr. Park: Again, depending on stage and the type of cancer. So there's still a lot of patients that we're not going to get, because 10 percent of breast cancer patients in this country alone annually, that's going to be about 20 plus thousand cases of breast cancer that is going to come back as metastatic incurable disease.

We know that we're curing this, because of these large clinical trials are recruiting additional patients with systemic therapies because of the large clinical trials that have randomized patients after local therapy, patients get randomized to placebo or chemotherapy. These studies take years to decades to complete. If you have enough patients, and enough follow-up time, you can show that chemotherapy, as an example, cuts the rate of recurrence, distant metastatic recurrence, by about 10 to 15 percent.

Now, that all sounds well and good. The problem is, when I see a patient in clinic for the first time, with newly diagnosed breast cancer and she's just had her local therapy, I don't know if she's cured or not.

The majority of them are. But I don't have a microscopic view or lens to let me know whether this patient actually has microscopic disease. So we tend to treat almost everyone. We treat 100 patients, let's say, to save 15, knowing fully that 70 don't need it.

Chris Riback: Because you can't necessarily get that microscopic view at this point.

Dr. Park: You don't know.

Chris Riback: You don't know.

Dr. Park: And you get one shot at cure. So that's why we overtreat.

Chris Riback: Yes.

Dr. Park: Now we've made some progress. There's the oncotype test and others that can help us decide whether this is really a type of breast cancer that is going to recur in 10 years, and, I should, is it even sensitive to chemotherapy? But in my view, it would be great to augment such tests with real-time evidence that a patient does or does not have microscopic disease. And therein lies the first kind of utility that I see for so-called liquid biopsies, which also has been funded by BCRF in the past.

Chris Riback: Yes.

Dr. Park: Looking at what we call self-reDNA ... it's long been known that all of our cells, whether they're normal or cancerous, shed or secrete small DNA molecules into the bloodstream. Nobody knows exactly what this is for. Some people have ascribed some function. Many people just think it's a waste product, including myself. I like to call this “cellular poop.” I've said that in some lectures.

Chris Riback:  That's the technical, medical term. We all know.

Dr. Park: Exactly. It's one of my favorites. The knowledge of this has actually been around for decades, but we didn't have technologies that allowed us to really assay for this. And so, finally, over the past couple decades now, we've gotten better in terms of DNA sequencing and looking for small amounts of DNA in whatever source that we can throw at the machines. In this case it's plasma, from the blood.

In fact, fetal maternal medicine, that whole field is about a decade ahead of us. There are now tests, believe it or not, where a pregnant mom can go to a doctor, get blood drawn, and have the fetal DNA sequenced from her blood. And so, we don't have to necessarily do amniocentesis and other more invasive procedures to look for genetic anomalies of the unborn child. That has really revolutionized the field in terms of screening for genetic disorders.

We're doing pretty much the same thing in our field, where we can now draw tubes of blood and find cancer DNA. The challenge though, for our field, has been making sure that these tests are going to deliver in terms of how they can guide our thinking and therapies for cancer patients. And that's really where the idea of clinical utility comes in.

Dan Hayes, who's also a BCRF funded investigator and former ASCO president ... I always quote him, because he says a bad test can be just as dangerous as a bad drug. I think that's really, really important and a powerful statement to remember, because we have to put tests or biomarkers as we call them, through the same rigor as we do for any drug, because you really want to make sure your test is going to be accurate in terms of who not to treat, versus who to treat.

And so we've, after years in the making, have really been the first to launch a prospective national multi-center trial, just like a Phase III drug trial, really to see whether we can use circulating cell free tumor DNA as a marker of residual disease for breast cancer patients. That study recently recruited patients. We're following them up ... this is again in early stage breast cancer and we, just like a drug trial, have to wait for follow-up data to really see whether this is going to work.

Chris Riback: You certainly don't suffer from a lack of activity or a lack of things going on.

Dr. Park: No.

Chris Riback: And on top of all of that, maybe we can talk about you for a second.

Dr. Park: Sure.

Chris Riback: You throw on top of all of that, a terrific new role and a move into Vanderbilt. Congratulations on that, by the way.

Dr. Park: Yeah. Thank you very much. I appreciate it.

Chris Riback: I shouldn't even say role, because you know, as one can judge by all the different things that you're doing, you've got multiple roles. You don't fill just one role. I bet you wish your life were that simple, just one role. But there is one role, or one aspect of what you do, that I want to ask you about.

Dr. Park: Sure.

Chris Riback: That's the Associate Director for Translational Research. I have loved, in these conversations, learning about translational research, because it's terrific to hear how folks like you take knowledge from one research area and translate it into clinical care, and get to see what's going on and the back and forth. I assume that has to be extremely rewarding to see how research translates. What does translational research mean to you, and why are you drawn to it?

Dr. Park: You know, I think that is such a great question. It's probably something we don't ask ourselves enough of. Translational research can mean so many things to so many people.

My own view of this, or how I've structured my career, is really taking what I've learned, both in my training as a PhD scientist as well as an MD medical doctor, and figuring out, How do we take observations from the lab and address important clinical problems that our patients would benefit from? And then vice versa, when we see patients suffering from cancer and certain aspects of it, whether it's disease-resistance or side effects from therapy, How do we tackle that problem from a laboratory perspective, to really have an impact? And so, those two are a back and forth, it's not a one-way street.

But it really is hugely exciting to think about how we could affect and develop new standards of care, new discoveries that are going to help cancer patients, both in the short term and in the long term. And you know, my example of the liquid biopsies for self-reDNA really speaks to that. You know, this is something where we've been working on that for about 10 years now and I was fortunate in that Hopkins, my former mentor, Bert Vogelstein, really kind of defined and created that field.

I kind of just took off from it, because it was so new and it was right upstairs from my own lab. I remember the first time we did some patient samples, I was just amazed that we could actually detect microscopic amounts of cancer in the blood. I went up to Bert's lab, I said, "You know, where we really need to focus, at least for breast cancer, is in the early stage for this over-treatment problem," because I see so many patients struggling with this ... are they cured? Are they not cured? You know, is the chemotherapy working? Do I even need it? These are fundamental questions that patients bring to us and really speaks to the unmet need that we tried to address with liquid biopsies in this trial.

It's a long process to get there. I'm the first to admit it, but it is incredibly gratifying thinking about how discoveries in the lab have made impacts into patient's lives with breast cancer. That's how I view translational research.

I think my role here really also speaks to that, because I'm involved with various aspects of not only what we call wet lab research, where you know, we look at the bench and we pipette little amounts of liquids and enzymes into tubes and try to answer questions that way. But also the bioinformatics group here, the people who actually can take computer data and big data and make sense of it, is really just incredibly strong at Vanderbilt. It's one of the best departments in the country, if not the world. And so, having that opportunity to interface with them and to also get to the clinical space has been hugely fun, in the very short time that I've been here. I view this as an opportunity, where I get to help direct and lead multiple different groups with incredibly world-renowned leaders into the problem of cancer. How do we use all the expertise and direct that into a focus that's going to lead for benefit for our patients? That to me is hugely fun and exciting to be here.

Chris Riback: It's got to be. And yes, there is so much going on. You touched on it. I mean, is there a more human question in the human anxiety and anxiousness that you, obviously, clearly, and people like you deal with every day, and want to try to relieve. But that question, Am I cured? Do I still have the disease?

That just goes to the heart of what you and people like you are trying to resolve. We think about it scientifically and medically and research-wise, but you really hit it, in my mind. At the core, there's just a human question, Doctor am I okay? And that's what-

Dr. Park: And it's incredibly frustrating from a physician perspective not to be able to tell patients whether they're cured or not.

That, I will tell you, is just as debilitating for many patients as having a diagnosis of metastatic disease, not being able to overcome the fear of recurrence. I've always been an advocate and proponent for patients to seek out professional help in that regard, because it is so difficult to live with that. You know, it's like the Sword of Damocles, you're just never sure when it's going to fall.

The truth is, in the majority of patients, it won't. It won't come back, as I was saying earlier. It is still something that anyone could understand how horribly difficult that is to live with. And so, I'm hopeful that with better technologies, that our clinical trial and others moving forward in this space, will really be able to address that as well.

Chris Riback: Yes.

Dr. Park: I think again, that's an important area where seeing patients has informed my direction in the lab.

Chris Riback:  That's wonderful. And you write about the psychological, if you will, but emotional and mental aspect of it, and I had a conversation on that with another BCRF investigator recently. Incredibly important work, as you identify.

To close out, how did you get into this in the first place? And I mean, going way back. I believe I read that you grew up in Michigan, which makes you another great Midwestern guy. But for you, was it always science? Was it puns? Was it potentially sitcom writing? Maybe a nickname writer.

Dr. Park: Maybe all of the above.

Chris Riback: Maybe all of the above. Well you did it.

Dr. Park: No, it was interesting. I grew up in this little town in Michigan called Saginaw, and I went to a public school system, that at the time wasn't really the strongest academically and I ended up almost on a whim, applying for and getting accepted to U of Chicago, which is the complete polar opposite. I was not prepared for this. My first quarter I was pretty overwhelmed, But thankfully, I quickly caught up.

Part of my decision to go to medical school was based on the fact that my father was a surgeon before he retired, and it was kind of funny because he kind of discouraged us from going to medicine. He said this is a really hard life and you've got to be passionate about it and love what you do if you're really going to do something like this. You can't do it because you think it's a safe secure job.

And I took that to heart, but I ended up making the decision on my own to become a pre-med. Part of becoming a pre-med, in most academic places at least, is that there's what I like to call check boxes. You have to shadow physicians, you have to do some volunteer community work. And even back in the 1980s, you should work in a lab, at least for a summer, if not a year or more, kind of to show that you have some interest in academic research and biomedical research.

I started in a lab in sophomore year at the U of Chicago. Hans Schreiber, who still has a lab there. And I was fascinated. It was a tumor immunology lab and I just thought, Wow, this is incredible. And I met MD-PhD students. I met people who were actually physician-scientists, including Hans, who's an MD-PhD himself. I heard about these programs that you could get into, to become MD-PhD physician-scientists. That really was my turning point. I really decided that if I was going to be a physician, I wanted to not just ... I wrote this in my medical school essay, I'll never forget it. I didn't want to just treat patients, I wanted to treat the disease.

Chris Riback: Wow.

Dr. Park: Meaning that I wanted to figure out how to solve the puzzle of the disease, including cancer. So at a very early age in this stage of my career, I was exposed to cancer tumor immunology. My PhD is actually in immunology. I like to tell the story that at some point, I just thought, Wow. Tumor immunology is just too hard. This cancer immunotherapy is never going to work, so I left the field. And as many know, I was far from right in my prediction.

Chris Riback: Yes.

Dr. Park: In fact, tumor immunology has become one of the hottest areas. It's taken several decades, but yeah.

I was fascinated by genetics, and so in graduate school, I was working on a retroviral project, where I was mutating genes in retroviruses. HIV was a very, very big area of research at the time and still is. And I got down to this point where I could define a pathogenic behavior of a retrovirus by mutating a single base pair or a letter of DNA, as we call it.

Chris Riback: Wow.

Dr. Park: That's when all of a sudden my light bulb moment came on. I was like, Genetics is incredible. One change in the DNA alphabet leads to a black and white difference. And at the time, Bert Vogelstein was tearing up the field in cancer genetics, publishing high-profile papers, one after the next, defining really the genetic, genomic landscape of cancers, particularly colon cancer at the time.

I applied in the lab and I got lucky enough to get accepted. The rest is history.

I mean, it was such an elegant idea that not only could we understand cancer at the DNA level, but because it was a disease of DNA, that afforded us the ability to target, because those DNA changes are unique to the cancer cells, compared to the normal cells surrounding them. So, if you have an abnormal DNA gene or mutated gene, you, by definition, or usually, will have an abnormal protein, since DNA just really encodes for proteins. Therein lies the ability to target those proteins that are causing cancer.

Now we have numerous examples of that. I think that's an area where I'm also trying to bring to bear here at Vanderbilt, in what we call precision oncology. This is also something I also started at Hopkins with our molecular tumor board, but I have the kind of capacity or ability here to really grow this to hopefully a world-wide level, where we're going to have the ability to really affect patients who have these mistakes in their DNA, that we have drugs.

I think that's one of the, again, hugely gratifying points of my job here, that we're going to be able to reach out to more patients, get them in here, understand what makes their tumors tick, and then hopefully find drugs that will help them.

Chris Riback: Well, it's very clear that sitcom writing's loss was medicine's gain. We're glad to have you on this side of the screen. And thank you. Thank you for your work, and thank you for your time with me today, Dr. Park.

Dr. Park: Oh, thank you. It's been a pleasure.

Chris Riback: That was my conversation with Dr. Park. My thanks to Dr. Park for joining, and you for listening. To learn more about breast cancer research or to subscribe to our podcast, go to BCRF.org/podcasts.

BCRF Announces Launch of New Precision Prevention Initiative

 

BCRF is dedicated to creating a future where women can benefit from the wide range of innovative strategies to reduce their breast cancer risk, but also to personalize risk assessment, screening and intervention. The newly launched BCRF Precision Prevention Initiative (PPI) was conceived out of this vision.

“There is an enormous opportunity for multidisciplinary research in breast cancer prevention,” said Dr. Judy Garber, BCRF Co-scientific Director. “Just as emerging technologies are transforming precision medicine, this new initiative seeks to capitalize on these new techniques and discoveries to reduce the incidence of breast cancer with all possible speed.”

Breast cancer mortality is at its lowest level in 30 years. This success has largely been fueled by advances in early detection and treatment. In contrast, our approach to cancer prevention has not progressed at nearly the same rate, as illustrated by the steady rates of breast cancer incidence over the same period.

“The overarching goal of this multiyear program is to fuel innovation and accelerate breast cancer prevention research by challenging the research community to think boldly and beyond their own fields to find new ways to get the answers faster,” Garber says.

For the 2019 funding period, BCRF is requesting applications that focus on prevention of the most aggressive breast cancers – those with the greatest likelihood of causing death. Applicants are encouraged to utilize the tools of precision medicine, artificial intelligence, epidemiology and immunology in addressing this challenge.

BCRF has long been at the vanguard of breast cancer research playing a role in every major advance in clinical care. We now aim to take the lead in precision prevention. The inaugural request for applications was made possible by a generous gift from Blizzard Entertainment. A copy of the full RFA can be found here.

Run with Team BCRF in the 2019 United Airlines New York City Half Marathon

 

For the very first year, BCRF has spots in the 2019 United Airlines New York City Half Marathon on March 17th. A long time charity partner of the TCS New York City Marathon, we are honored to expand Team BCRF and have runners take on the challenge of participating in this monumental race to support breast cancer research.

For those interested in applying to be on Team BCRF in the 2019 United Airlines New York City Half Marathon, please fill out the application form and take note of the conditions below.

Each participant is required to raise a minimum of $1,500 for BCRF. In return, the race entry fee will be waived and each runner will be provided with a Team BCRF shirt, as well as pink ribbons and bracelets to advance their fundraising efforts.

All applications must be received by December 17, 2018 and will be reviewed on a first come first serve basis. The names of selected runners will be announced no later than December 31, 2018.

For any additional questions, please email Christine Ward at cward@bcrf.org

Three Inspiring New Leaders Join BCRF’s Advisory Board

 

BCRF‘s Advisory Board—a cohort of female ambassadors whose dedication to research has changed the very face of breast cancer—is proud to welcome three new additions. Lisa Harbert, Sinesia Karol and Pheodora Shin join this dynamic, powerful board, strengthening BCRF’s ability to propel research forward, faster.


Sinesia Karol is Founder and Creative Director of her namesake international luxury swimwear line. Sinesia Karol has been a devoted friend and supporter of BCRF for over a decade. Having lost a loved one to breast cancer, Sinesia and her husband Bill are personally dedicated to ending breast cancer. They have served as Co-chairs of the Boston Hot Pink Party for the past three years, playing a pivotal role in the fundraising success of this event, and supporting BCRF’s continued growth in New England.

 

Pheodora Shin, MD is a physician who lives in New Jersey with her husband Myung, and their three children, Grace, Ryan and Matthew. She was diagnosed with breast cancer at age 45, after both her mother and aunt had been previously diagnosed. Dr. Shin and her family began supporting BCRF in 2015, when they attended the NYC Hot Pink Party to celebrate Pheo’s five years of survivorship. Since then, she has been a dedicated supporter and ambassador for BCRF, sharing her story publicly to help inspire and encourage generosity from others.

 

Lisa Harbert is an entrepreneur and former HR executive with a passion for supporting BCRF’s mission to end breast cancer. Lisa and her husband, Ted, have served on the Host Committee for the Hamptons Paddle & Party for Pink for several years; they are also Agenda Advisors for BCRF's young professionals organization, The Pink Agenda, inspiring philanthropy in the next generation. Lisa has generously contributed her time and talents to ensure the sustained success of several BCRF fundraising events and looks forward to participating as a member of the Advisory Board to help advance the world’s most promising breast cancer research.

BCRF moves forward everyday in its work thanks to the cumulative efforts of its leadership, researchers, supporters, and staff. Learn more about them at bcrf.org/about.

Investigating Breast Cancer: Dr. Hedvig Hricak

 

Subscribe to BCRF Conversations here:

Dr. Hedvig Hricak, recipient of the Delta Air Lines Award, has been a BCRF investigator since 2004. Dr. Hricak is, among many other roles, Chairman, Department of Radiology at Memorial Sloan Kettering Cancer Center. She was honored by BCRF with the 2018 Jill Rose Award for outstanding research excellence. As you will hear, Dr. Hricak is extraordinary – not just in her work helping merge imaging technology with molecular medicine, but also in her teaching across borders. Among her wonderful lines in this conversation: “The best thing in life is to give,” and “The richness of life is in diversity.” Another one: “You are only as good as your tomorrow. So you have to continuously reinvest yourself. You have to learn and believe that with your experience, you’ll make a difference in patients’ lives.” Listen to this podcast, and you’ll know exactly what she means and the difference she makes in patients’ lives. 


Read the transcript of the conversation below:

Chris Riback: I'm Chris Riback. This is Investigating Breast Cancer, the podcast for the Breast Cancer Research Foundation and conversations with the world's leading scientists studying breast cancer prevention, diagnosis, treatment, survivorship and metastasis.

Chris Riback: Dr. Hedvig Hricak: is, among many other roles, Chairman, Department of Radiology at Memorial Sloan Kettering Cancer Center. She also recently was honored by BCRF with the 2018 Jill Rose Award for outstanding research excellence. As you will hear, Dr. Hricak is extraordinary – not just in her work helping merge imaging technology with molecular medicine, but also in her teaching across borders. Among her wonderful lines in this conversation: “The best thing in life is to give,” and “The richness of life is in diversity.” Another one: “You are only as good as your tomorrow. So you have to continuously reinvest yourself. You have to learn and believe that with your experience, you’ll make a difference in patients’ lives.” Listen to this podcast, and you’ll know exactly what she means and the difference she makes in patients’ lives.

Chris Riback: Dr. Hricak, thanks for joining me. I appreciate your time.

Dr. Hedvig Hricak: Thank you for having me.

Chris Riback: We should start, of course, with congratulations. You recently were honored with the 2018 Jill Rose Award for outstanding research excellence for your seminal contributions towards merging imaging technology with molecular medicine from BCRF. What was the event like? How did that feel?

Dr. Hedvig Hricak: The event was much more than wonderful. The event was very, very emotional as well. The reason is we all, all the 300 researchers that BCRF has so ably led by Larry Norton and by Judy, but all the attendants in that room, we are all committed to one and only cause. That is really to help women with breast cancer, to make sure that the breast cancer is, I don't like to say will ever be totally cured, but can be a chronic disease that we can all learn how to live with.

Chris Riback: What drove the emotions? Looking back on the career being surrounded by so many other people dedicated completely to the cause, the women in the audience, the women you were thinking about, what drove the emotion?

Dr. Hedvig Hricak: Personally, the emotion, my personal beginning in the truly attachment, respect, and tremendous love for the mission and scope of the BCRF. As well as my respect for the fellow BCRF researchers, but also because BCRF always in my heart and my soul reminds me of Evelyn Lauder, its founder. You know Evelyn, I have tremendous admiration for, Evelyn. I remember her enthusiasm, her warmth, her friendship, her dedication to the cause of BCRF. She was a wonderful, wonderful woman and truly a mentor. And she embraced me from the day I came to New York, and it was very very special. So yes, for me in at one moment even brought tears to my eyes was just remembering how I would not stand there if it wasn't for Evelyn. If it wasn't for support of Larry Norton and also if it wasn't for wonderful, wonderful department that I have at MSK, and our breast imaging that was always supportive of the initiatives of the grants, of the new ideas.

Dr. Hedvig Hricak: You never ever achieve anything by yourself. You always, I feel I was really lucky to be at the right place at the right time, and met such wonderful, wonderful people. Yeah, so it is, it was very emotional.

Chris Riback: Well, you sound wonderful about it right now, and it must've been just a powerful and just memorable and terrific event. So congratulations to you and to them and you know when you talk about, the benefits that you got from the help of others, that helps move us very smoothly to the benefits that you have created for others as well. Particularly, in the areas of imaging and cancer. So let's talk about that.

Chris Riback: Why is imaging for cancer, but in particular breast cancer, and this is you know some of the core of the work that you have dedicated your career to, why is that so hard?

Dr. Hedvig Hricak: First of all my expertise and my longtime passion is women's imaging, but in women's imaging it is much more in the field of gynecology. Both uterine as well as ovarian cancer. And my other expertise is in prostate cancer and for both of that my work started way, way back with the beginning of magnetic resonance. However, I deeply care for improvement in cancer imaging and of course being involved with women's imaging from the very beginning of 90's when the entire movement started. Breast cancer imaging was always very important to me.

Dr. Hedvig Hricak: Regarding your question, why is imaging for cancer, for breast cancer so hard? It's actually not hard if you have proper training and expertise. And we need to understand that that expertise in oncologic imaging and imaging breast cancer has to include knowledge about imaging technology. So for example in breast cancer, you have to know how to perform and interpret ultrasound MRI, or Magnetic Resonance Imaging, and mammography. And then that is not enough, that expertise has to include knowledge of the disease. As radiologists we need that knowledge to understand which imaging to use when. And the second critical, is that the clinical questions that needs to be answered so we can make our report clinically relevant. There are many studies in the literature that show that when the same exam of breast imaging, is re read by a specialist that has training and expertise and the clinical knowledge, they make a difference in patient management in 20 percent, and as high as 35 percent.

Chris Riback: Wow.

Dr. Hedvig Hricak: That is huge, and it shows you how important that training and expertise are. And in radiology, there is a tremendous convergence of technology, you have to know disease and interpretation, how to report requires special education as well. And that is probably a problem nationwide, that we just need more well-trained breast imagers.

Chris Riback: That's incredible, and an incredible statistic. Is the focus, do you feel like the focus is there in terms of the training? Because what a difference it makes, you know what I'm hearing you say is absolutely, getting the imaging is imperative, but it's only half the story. You then have to have the right reading and the right clinical interpretation. Is, have you sensed...

Dr. Hedvig Hricak: And the knowledge of the disease. You know everything in life is evolution and dynamic. So the way we, the questions that were asked from radiologists in breast imaging ten years ago are different than today. They're much more granular and detail today because therapy has changed. Options have changed. We are now entering the era of reproductive screening, and to be able to contribute to that reproductive screening, you as the radiologist have to evolve as well. So those are elements that are critical, it is not you can learn fifteen years ago, and you are done. Absolutely, not. Everyday you are better and better, and you evolve with the science that's coming up.

Chris Riback: So a question on that evolution and tying it back to something you were saying earlier how your personal history might've been a little bit stronger or at least originated in it sounded like gynecology and prostate cancer, but you have been able to apply your skills and learn. And I know that you are a continual learner, learn in different areas. One of the most interesting things that I've learned in these conversations with scientists and researchers like you, is how you connect, people like you connect your work across cancers. For me, you really feel like the ultimate investigators, finding clues in one part of the body and divining how they may or may not apply to other parts. That seems to be consistent with your approach. Is it? Can you talk about how your work in one are of cancer may have helped you think creatively, or act directly in other cancer areas such as breast cancer?

Dr. Hedvig Hricak: Sure, for example I already said that I started with MRI of prostate cancer, and there are great similarities in the biology between prostate cancer and breast cancer.

Dr. Hedvig Hricak: So, in both it is a challenge. One of the very acute challenges is to determine tumor aggressiveness. And whether in fact the cancer may be non-aggressive for example in prostate cancer, as you know many patients are now considered for active surveillance. Which mean, instead of being treated immediately either by surgery or radiation therapy, the tumor is monitored to determine if it is progressing. Because many more men die with cancer, than of prostate cancer. So that decision to choose active surveillance is based on a combination of laboratory tests, pathology, and MR imaging. And now today sometimes we add information from genetic testing. A very similar challenge is now evolving, emerging in breast cancer. Not all cancers, even if they are genetically very similar are going to be aggressive. So one of the tasks for the next few years is how to identify a [inaudible 00:13:28] group of breast cancer patients that perhaps does not need aggressive treatment. And it has already changed, already not everybody with breast cancer needs chemotherapy, but moving forward we may be even less aggressive.

Dr. Hedvig Hricak: Another part is, that androgen receptor imaging and androgen receptor plays a big role in prostate cancer. And We have developed androgen receptor imaging to really search and evaluate metastatic prostate cancer in prostate cancer. But we know through evolution, especially with late state metastasis in breast cancer that many of those cancer, androgen receptor, they all were expressed, androgen, or AR receptors. So now the next movement, is to apply that androgen receptor molecular imaging that was developed for prostate cancer in patients with breast cancer, because up to 70 percent of patients express androgen receptors. You can actually treat them with androgen therapy, but you have to identify which sub-population will really benefit.

Chris Riback: See, this is just another example of what is so fascinating for me about these conversations. I would never have suspected that there were ways to translate learnings from prostate cancer to breast cancer. That just wouldn't seem, to a lay person that doesn't seem intuitive and yet that's central to some of the work that you've done.

Dr. Hedvig Hricak: And some of the advances, yes.

Chris Riback: Can we talk about another area of advances that you've made, in another kind of it connects with your theme of bringing knowledge from one place, maybe you know from one part of the body to another, but also from one location to another. And that's a cross border collaboration. This is a another just wonderful aspect of your impact and it's incredible work. Tell me how does it work, how have you connected a global network of breast imaging radiologists who are working together, and I'm quoting here 'with a single goal of improving breast cancer patient outcomes worldwide. How have you created that cross border collocation?

Dr. Hedvig Hricak: Evelyn Lauder and Larry Norton were absolutely crucial in the sense of, to make this a reality. Very often in life we have a wish list, we have a hypothesis or an idea, but unless you have a resource to make that happen, it always stays a dream. So Evelyn and Larry while they very much believed in research, development, and innovations how to change the cancer care of tomorrow, they understood that we are one global world, and medicine has no wells. So, therefore, all the way back in 2004, I was awarded an educational grant for really working worldwide and making sure that women around the world have access.

Dr. Hedvig Hricak: So the effort of global education is [incredibly] important. Just like Evelyn and Larry, I deeply believe it is our social responsibility in the ethics of our profession that every patient, no matter where they are should be helped and taken care of. And we understand that resource that we have in the western world is not the same as those available in a low middle income country. However, through education and training, you can make sure that those low and middle income countries have essential access to expertise and that expertise means training radiologists, so they know how to image, when to image, and how to interpret. And everything is global, so outreach and sharing our knowledge and that's really what academia can give and I think it is our responsibility as well.

Chris Riback: It's got to be an incredibly rewarding component of what you do.

Dr. Hedvig Hricak: Yes, it is. It is, if you the letters sometimes that you receive. People you help that you'll never know their faces, it is very very rewarding.

Chris Riback: What got you into this whole thing? How did you become a scientist? Was it always science for you growing up? Did you have other aspirations at some point? Tell me more about your background.

Dr. Hedvig Hricak: So, I love science, but when I was in high school and early on, I really liked mathematics and physics, and science and any analytics. And then I thought how to apply that love for science into medicine, because medicine actually it's an ultimate science. Because you combine everything from human factors, to mathematics, to physics, to biology, and it's just. It's so diverse, and combining then that love of biology and combining that with love of physics and mathematics, I went into diagnostic radiology.

Chris Riback: Did you start your career oversees and then came here? Or was it always here in the U.S.?

Dr. Hedvig Hricak: I started my residency in my home country, Croatia, but then I repeated everything in the United States.

Chris Riback: There's another effort that you are a part of that I want to ask about quickly before, before I let you go and that's the CCNY Memorial Sloan-Kettering Partnership for Research, Training, and Outreach. The goal of this training program is focused on minority students and it just feels like a way, and you'll correct me because maybe I'm interpreting it wrong. But on the one hand you have this cross border educational effort, you know reaching out to all corners of the globe, and then similarly in I guess, based in New York City, but you'll explain to me if it goes beyond that. You're focused on bringing in minority students as well, and crossing borders and expanding reach locally as well. Am I interpreting that correctly?

Dr. Hedvig Hricak: Yes. So it is the same passion, I believe that it's really important to make special effort to reach out and provide opportunities to those who may not otherwise have them. And it is important to make that special effort to reach out and diminish disparities in our own country, not just abroad. So, majority of the students at the City College of New York, especially those from under represented minority communities, they really came from socio economically disadvantaged, often disadvantaged family. Many are first generation college students, or they are from immigrant families.

Dr. Hedvig Hricak: Now this partnership is able to done, through the NIH funded partnership, with the City College. And the main goal is to mentor and support students offering them resources, MSK for stem and that is science, technology, engineering, and math program, as well as behavior science. So they can successfully just giving opportunity, so they can successfully conduct biomedical and behavior research. And then we also mentor them, we provide them guidance with regard to their career decision. An overarching goal is to increase the number of competitively trained underrepresented minority who enroll and complete, either in the PHD or combined MD/PHD program. The richness of life is in diversity, and you have to help them get there.

Dr. Hedvig Hricak: We do a very similar program with the New York City Department of Education, and this program is now going on for 15 years. Where, it's also an outreach that helps underrepresented minority students in New York City high schools. Now, in order to be enrolled in our program they have to write an essay, and then we grade the essays together with the teachers. So it's a program that really gives back to the teachers, to city of New York, and those high schools are such a pleasure to work with. It's program in science of course, and it's going on for 15 years, and it's getting bigger and bigger every year. And more and more popular, so as a person, as you and I, the best thing in life is to give. When you give, you receive much more than you ever thought it's possible.

Chris Riback: That's terrific. It's got to be an incredible amount of fun and so that of course makes me think as I you know prepare to let you go, so you do that incredible work with those students. You have created and have helped create this cross border effort. You are a pioneer, and a leader around imaging and then the interpretation of imaging across multiple cancer forms. You've won, you know, earned I should say, enumerable awards, including the most recent one from BCRF. I certainly hope you don't think me ungrateful Dr. Hricak, but what's next?

Dr. Hedvig Hricak: Well, there's always next. One of my guiding lights, that my faculty sometimes jokes about. I always say you are only as good as your tomorrow. So you have to continuously reinvent yourself. You have to learn and believe that with your work and experience, you'll make a difference in patients' lives. Not using tools of the yesterday, but using tools of today and tomorrow. So one of our big nexts, is supporting the development of theranostics. That's a new field which is beyond molecular imaging, because it actually combines molecular imaging and therapy.

Dr. Hedvig Hricak: One big part of precision medicine in order to choose a proper treatment you really have to have all the precision details about the disease. But theranostics approach where we develop targeted molecular imaging agents, so we can image and understand cancer biology. And then we develop drugs that are directed to the same target. So and very often they're attached to the same main molecule, or the agent that will act. So this provides the ability to see not only whether the drug has bonded or reached the target, but immediately shows you the effect within a few days that that drug is having. So the theranostics, is the next big step in allowing targeted treatment to be based on evidence, and the specific features of individual patients.

Dr. Hedvig Hricak: It's a dream, it's starting with an idea and a hypothesis, but we already have theranostics on the neuro endocrine tumor, which is superb. We in Europe, they're widely using theranostics for prostate cancer treatment, it's called the PSMA theranostics, hopefully we'll have that soon in this country. And one of the big dream is now, having a theranostics for breast cancer as well. And this is where that cross fertilization across different cancer, you learn you know, you learn a little bit how to do it and then you move forwards, to another horizon.

Chris Riback: That's a wonderful way of putting it, and it sounds like, you say that it is a dream but a wise and terrific scientist recently told me that, if you have a dream with the proper support those dreams can become reality.

Dr. Hedvig Hricak: And this is exactly how the educational grants started and all the others. You have a dream, you believe in it, and you persevere, and it does become a reality.

Chris Riback: Thank you. Thank you for this work, for the conversation and everything that you have done. I really enjoyed the conversation. Thank you.

Dr. Hedvig Hricak: Thank you.

Chris Riback: To learn more about breast cancer research, or to subscribe to our podcast, go to BCRF.org/podcasts.

 

Research is the Reason I Have My Miracle Baby

 

When Kelley Tuthill learned she was pregnant with her third child, the news came to her as a two-fold surprise.

“Life takes you on a lot of unexpected twists and turns. Breast cancer was definitely one of them,” she says recalling her diagnosis 12 years ago. “Then to have a beautiful baby arrive unexpectedly was both the shock and gift of a lifetime.”

In 2006, Kelley was diagnosed with breast cancer. She had given birth to her second child six months earlier. It was the Friday before Christmas. She was 36 years old.

“When I say I wasn't expecting the diagnosis, I was blindsided,” she says.

After undergoing surgery, chemotherapy and radiation, Kelley successfully completed her treatment in 2007 and has remained in remission ever since.

Her tumor, which was HER2-positive, was aggressive. It was successfully treated with traztuzumab, a targeted therapy known as Herceptin – a medicine developed thanks to early clinical trials supported by BCRF funding. The drug has been proven to decrease the risk of recurrence in HER2-positive cancers by 50 percent.

“When you look at the importance of research, the targeted treatment was there when I needed it desperately. And it's the only reason why I'm alive,” she says.

Not only did the targeted therapy put Kelley’s cancer in remission, but it gave her a chance to be a mom for a third time. However, this was not a path she could have predicted.

For five years post-treatment, Kelley took tamoxifen, an estrogen-blocker, to prevent the cancer from reoccurring. Given her course of treatment as well as her age, she did not expect nor plan for a third child.

“I had a baby nine years after I was diagnosed with breast cancer. At the time of my diagnosis, I thought I was going to lose my life. Never did I in a million years think that I would be able to give birth again and have another child,” Kelley says.

Since then, Kelley has become a strong advocate for breast cancer research.

“I always say BCRF not only saved my life, but they made it possible for me to have another life,” she reflects. “So I truly owe this organization a huge debt of gratitude.”

While research advancements helped Kelley move past her disease, more breakthroughs need to be made to help everyone impacted by breast cancer.

“I want there to be a world ahead for everyone's daughters where they don't ever have to worry about this disease,” she says. “Research is how we're going to get there.”

 



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