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Investigating Breast Cancer: Dr. Eric Winer

The "de-escalation" of therapy
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How should we – patients, family, doctors – consider the careful balance in identifying patients who might benefit from less rigorous course of treatment?

Dr. Eric Winer, a BCRF investigator since 2003, studies this concept. Known as “de-escalation of therapy,” this form of personalized medicine challenges the “one-size-fits-all” approach to breast cancer treatment. His current BCRF-supported study aims to improve quality of life by reducing post-surgery chemotherapy in carefully selected patients with early-stage HER2 positive breast cancer and an excellent prognosis.

Dr. Winer is Professor of Medicine at Harvard Medical School and Chief, Division of Women's Cancers and the Thompson Senior Investigator in Breast Cancer Research at Dana-Farber Cancer Institute. He is also the recipient of BCRF’s 2019 Jill Rose Award for scientific excellence and the Westchester Women’s Award in honor of Marla Mehlman.

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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.

How should we – patients, family, doctors – consider the careful balance in identifying patients who might benefit from less–rather than more– therapy?

It’s a tricky thing. After all, this so-called “de-escalation of therapy” comes with challenges for both patients, who may fear a recurrence and for doctors, who want to give their patients the best care. 

But this is exactly challenge that Dr. Eric P. Winer currently studies, researches and acts on.

Dr. Winer has devoted his professional career to the treatment of individuals with breast cancer and breast cancer research. He has designed and led phase I, II, and III clinical trials. His current clinical trial investigates reducing post-surgery chemotherapy use in patients with excellent prognosis. This study will lay the groundwork for a large international trial aimed at reducing chemotherapy use in patients with good prognosis.

And as compelling and significant as the work he does is, as you’ll hear, Dr. Winer’s personal story is also compelling – and provides some context for how he thinks and who he is.

Some background: Dr. Winer is a Professor of Medicine at Harvard Medical School and, among other roles, Chief Clinical Strategy Officer; Chief of the Division of Women's Cancers; Chief of the Division of Breast Oncology Center at Susan F. Smith Center for Women's Cancers; and the Thompson Senior Investigator in Breast Cancer Research at Dana-Farber Cancer Institute. He is also a Member of the BCRF Scientific Advisory Board and has been a BCRF Investigator since 2003. Beyond these roles, Dr. Winer earned the 2019 Jill Rose Award for scientific excellence, as well as the 2019-2020 Westchester Women’s Award in honor of Marla Mehlman – about whom I’d like to add a personal note:

I know that most of the incredible listeners of this podcast have a personal connection to breast cancer. Many may have lost someone they loved. Among my connections was with Marla – a wonderful friend and better wife and mother to Jon and their three girls. I’m honored to present this conversation in her memory.

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

Dr. Eric Winer: Thanks for having me.

Chris Riback: I have to begin with congratulations. You recently were inducted into the 2019 class of Giants of Cancer Care. Now you're the doctor, but I'm the communications guy. Have you thought about changing your business card and making it just Dr. Eric P. Winer, Giant?

Dr. Eric Winer: I think I'll hold off for a little while on that one.

Chris Riback: A little bit? Okay. Just keep it in the back-

Dr. Eric Winer: Just a little bit. I don't know that I think of myself as any kind of giant. You know, there are a lot of people who spend a lot of time devoted to cancer and taking care of patients with cancer. Again, I'm just one of many.

Chris Riback: I know, there sure are, and I'm sure you don't. Let the record show, I was the one who put the idea out there. It had nothing to do... That was me, that was not you. But it looked like, you know, a terrific award.

We're not here, of course, just to talk about your awards, but I want to talk about another one, not because of the award but because of your lecture. The lecture there that you did, I think in getting to read about you and learn about the work that you've done and, frankly, who you are, I think that lecture gets to the heart of your work and your approach. You were the 2018 recipient of the Brinker Award for Scientific Distinction in Clinical Research.

Very often, researchers earn this, it's a prestigious award and they discuss breakthroughs in new aggressive treatments: New drugs, new ways to actively attack cancer. However, you took, my understanding is, the opportunity instead to explain your views 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. Explain that to me.

Dr. Eric Winer: When I think about the challenges in breast cancer in 2019 in big terms, I think of three major challenges. First is the challenge that there are still breast cancers that become resistant to all of the treatments we have. There are 40,000 women in the United States, and about 10 times that many worldwide who lose their lives from breast cancer each year. For many of those women, the problem is that we don't have the right drugs. Either we should be giving more or, perhaps a better way to think of it is we need different drugs. So those aren't people where we need to back off. They're people for whose cancer we need to come up with better therapies.

Then there's the second big challenge, which is that not everybody around the world or in the United States or even in the cities of Boston and New York where you and I are at the moment have equal access to care. Healthcare disparities are a huge problem. I often tell people that anything that makes someone a little bit different from the norm puts them at risk for a healthcare disparity. So if you're white and middle aged and have a reasonable education and health insurance and good social support, you are so much more likely to do well with your cancer than if you're un or underinsured, lack education, are a person of color. And so these social factors are absolutely critical, and one can only begin to guess at the number of lives that are lost each year because not everyone has the same care that you might want for your loved one.

Chris Riback: Yes.

Dr. Eric Winer: But then finally, and it's easy to get focused on the first two, but finally there's a very large group of women with breast cancer who are being substantially over treated. By that, I mean we're giving more than they need. Because our treatments oftentimes have side effects and toxicities, that means creating a whole burden for these patients that they don't need. And so, while we're looking for new and better treatments and we're trying to solve societal problems, we also need to be looking at ways in which safely and carefully we can begin to back off in some areas.

Chris Riback: On that last point, a couple months ago I had the privilege to talk with Dr. Joseph Sparano. I know that you know his TAILORx study, the largest breast cancer treatment trial ever conducted, showed no benefit from chemotherapy for 70% of women with the most common type of breast cancer. On that last point, are you referring necessarily specifically to TAILORx, or that study, or that plus other studies that have been done?

Dr. Eric Winer: I gave a lecture yesterday morning about this same subject, and TAILORx was one of the two examples I used. So just to be clear, this was 70% of patients who had no negative estrogen receptor positive breast cancer, because there still are many women with estrogen receptor positive breast cancer who, either because they have multiple positive lymph nodes or because they have a slightly different subtype of their cancer may need chemotherapy, but the study did definitively identify a very large group of women for whom we just don't need to give chemotherapy, because not only do they have a very favorable prognosis without it, but we can't even make that favorable prognosis any better by giving it.

Chris Riback: This is about the point in the conversation where I would normally dive right into your current research. But I don't think it's possible to understand what do... It's my speculation just in terms of reading and learning about you, I don't think it's possible to understand what you do and why you do it without understanding who you are. So can we dial back the clock just a little bit? You've spent a lifetime, starting when you were just four or five years old, with doctors and in hospitals. What did it mean to have hemophilia as a young boy?

Dr. Eric Winer: I was born with hemophilia. My grandfather had hemophilia and lived to be 45, he died a few years before I was born. As a kid, it meant that I had very frequent bleeding problems. Now this isn't bleeding the way people think of bleeding. It's not cutting yourself and having a large amount of blood that's seen. It's mostly bleeding into joints. I had that very, very frequently.

We had very limited treatments when I was a small child, and I used to miss school about a third to a half of every year because I was either having or recovering from some bleed in some joint. In truth, I couldn't do very much physically. I couldn't participate in sports, and I had a relatively limited early childhood until I was about 11 or 12, when some new treatments came out that involved taking an intravenous injection every other day, and these were factor VIII concentrates that essentially made me into a much more normal kid.

These factor VIII concentrates were made from human plasma, but what was somewhat unique to this product was that they would be made in huge vats, and in any bottle that I received that then had to be reconstituted, there was blood from about 10,000 different people.

Chris Riback: Then to become a doctor, apparently you thought the best path was to double major in history and Russian East European studies. I'm not going to lie, Dr. Winer. Yale has an awfully strange pre-med program.

Dr. Eric Winer: Yes, well, I didn't take any pre-med courses as an undergraduate. My experience having hemophilia and spending much of my childhood at Children's Hospital in Boston made me intrigued by the idea of being a doctor and I always thought I would, but then I got to college and I said, "Well, science may not be my strongest area. Maybe I should do something that I actually like a little bit more." So I studied history, and then I studied Russian history, and much of my interest in Russian history also came from the fact that the son of the last Czar of Russia actually had hemophilia I sort of had a personal interest there, too.

Dr. Eric Winer: But I ultimately decided I still wanted to be a doctor, and I went back and I took pre medical courses and went on to medical school and did my training.

Chris Riback: The understanding that you had, I think, as a child and the positive impact that factor VIII made, you also know what it's like to live with a life threatening disease, as well as the power of scientific research, discovery, and medication, don't you?

Dr. Eric Winer: I do, although I'll tell you that when I was in medical school, I was driving in a car with a friend. She said, "Well, your hemophilia isn't really an issue anymore. You seem totally normal." I said, "Yes, you know, I'm pretty lucky. But you never know what it's going to mean to inject this stuff into your body every other day for years and years." What ultimately happened, as happened to virtually everybody with severe hemophilia in the late '70s and '80s is that, again like everyone else, I contracted HIV.

Chris Riback: As you think about your approach to medicine and other of your colleagues' approach to medicine, do you feel like because of your history you come at it differently? Do you have... I mean, you've got to have a different set of eyes. You've been on both sides of it since you were four or five years old.

Dr. Eric Winer: Yes. Well, I do. You know, my medical history, which don't need to go into all the details, but became even more complicated over the next 20 years. I often say I'm the poster child for scientific advances and what they can bring, and complications of therapy and what our treatments can cause, because over the course of the past 20 or 30 years, have benefited from the dramatic advances in treatment for HIV, which are really sort of incredible, but also some complications from the therapy that lead to additional problems and some surgeries and all sorts of things.

Dr. Eric Winer: But I think that, and as I've told people, I think at age... I'm old... at age 62, I think I have a better chance of being alive 10 years from now or 20 years from now than I did when I was 52, 42, or 32. I mean, I'm just a really lucky guy. But I also don't want people to misunderstand, because I don't think I'm particularly special. I think most people have something in their past or have experienced something that has been very much a life altering experience, and when you scratch below the surface, most people have something. So sure, my experiences have influenced to some extent my interest in certain aspects of medicine and my practice of medicine, but I don't think that that's necessarily so distinct from a lot of other people.

Chris Riback: I understand that, and I agree with that. Everyone has a story. Everyone is... It never ceases to amaze me when, you know, talk to just about anybody. Once you, in your words, scratch past the surface, there's something in their life that has impacted them. I guess that's part of life for all of us. I'm sorry, go ahead.

Dr. Eric Winer: No, no, no. I was just going to say, the hard thing that was a little bit unique with having HIV in the late '80s and '90s, and this has of course I think allowed me in some ways to understand a little bit what some of my patients experience, is that it felt pretty hopeless at that time. It felt like there was a very high likelihood this was going to take my life in a way that wouldn't be very pleasant.

Dr. Eric Winer: And then there was the added piece, which was just, you know, really challenging for me and for my family, which I think people with cancer used to feel more than they do now, thankfully, which is I and we really felt stigmatized. And so, I didn't feel like I could talk about my health with really anybody, because I was afraid that if the parents of children's friends knew that their father had HIV that they wouldn't be invited over to play anymore, because there was just such craziness around all of this. That was certainly very challenging.

Chris Riback: Yes, and that has been, as I've read about the history of cancer, that has been clearly one of the most significant transformations of the view of cancer in the public, and that changed as well, obviously, with HIV, and it changed through-

Dr. Eric Winer: Totally. I mean, I never would have talked about this. I mean, I don't talk about my health with patients, because I think they're there for me to help them, not for them to listen to my stories. But at this point, you know, I'm out there enough and have talked about this enough that I'd say at least half the patients who come in to see me have Googled me and have found the stories. You know, maybe there are some people who have chosen not to come see me because of it, but I don't think there are many. Whereas in the 1990s, I'll bet that if it were out there at the time that I had HIV that, you know, three quarters of the people who came to see me probably would have found a different doctor.

Chris Riback: So let's talk about the work that you're doing for your patients, and let's talk about your current study. What is the current one size fits all treatment for HER-2 positive breast cancer and what's the goal of your study?

Dr. Eric Winer: Yes. The one size fits all treatment is a moderate amount of chemotherapy in combination with one or, more often, two antibody therapies directed specifically to the HER-2 protein which is present on HER-2 positive breast cancers. What our study does is it takes advantage of work that's been done over a number of years that suggests very strongly that if you give a patient treatment before surgery either with treatment for HER-2 positive breast cancer or treatment for triple-negative breast cancer, whatever the treatment is, if a patient's cancer goes away entirely with that course of treatment, and when you do surgery you find no cancer whatsoever, that patient turns out to have a very, very favorable prognosis.

So knowing that, what we're doing is giving a more limited amount of chemotherapy in combination with antibody therapy for 12 weeks, and then doing surgery. If at the time of surgery there is no additional cancer, then the plan is for those women not to receive any further chemotherapy and simply to be followed.

Now to be clear, this is a pilot study to see if we can do this and if people will accept it. And it's a study that's being done in preparation for a much larger national study that will address the same question, and we're just making sure that it's going to be feasible doing it before that larger national study is done. That study will be done under the auspices of the National Cancer Institute and will be conducted around the country.

Chris Riback: And that's what I was going to ask, is how far are you into this and do you have any initial data? Is anything aligning with your hypothesis or raising questions for you around your hypothesis?

Dr. Eric Winer: Our primary hypothesis is that this would be feasible. I mean, this is asking is it possible to do this. My preliminary answer would be yes. The study that we're doing very much with support from the BCRF, thankfully with support from the BCRF, is a study that will involve 117 women. To date, in the past six months we've enrolled 47 women, so we're almost halfway in a very short period of time. In fact, I got a message from our IRB, which stands for our institutional review board, telling me that we had a study that was enrolling more quickly than most studies, usually the problem is they enroll too slowly, and just wanting to check with me to make sure that it was okay. I said, "Yes, it's great."

Chris Riback: Those are the problems you want.

Dr. Eric Winer: Right. You know, it appears that about as many women are having all the cancer go away as we would expect. People who have all the cancer go away are then, as we predicted, with their doctors choosing not to get additional chemotherapy. I think it says that we're going to be successful, at least in a very preliminary way, because we have to finish the study if we're going to successful in terms of the national study, in terms of accrual, and in terms of being able to test where those women in fact do as well as we think they're going to do.

Chris Riback: I'm interested, for so many people with breast cancer, for their families as well, the quality of life is such a question, important question, and balance, balancing aggressive care and quality of life. I'm wondering about your conversations with the patients. I mean, after all a de-escalation of therapy comes with challenges for both patients who fear recurrence and for doctors who want to give their patients the best care. How do you explain to the patient, "You have breast cancer and despite everything you might have read or heard about you need to be aggressive, I think that for you, you should do less right now, not more." How do patients react to that?

Dr. Eric Winer: To begin with, for patients who don't have all the cancer go away, we do give more therapy. And for the patients where all the cancer does go away, we explain that additional therapy has side effects, that the preliminary evidence is that the outcome will be very favorable... Sorry, I've got to just start that again, because I got distracted by my page. The preliminary evidence is that without additional chemotherapy, the prognosis will be very favorable, and that while we can't say with absolute certainty that they may not be giving up a very small benefit, that we don't think that it's going to be substantial. But ultimately, it's up an individual patient making a decision with her doctor, or in the case of one person, his doctor, since we have a man in the study.

And I think these studies of de-escalation are complicated. They're complicated because people don't want to leave treatment behind that could be helpful. I think that's true of doctors who, I think, if anything tend to be even a little more reluctant than patients. Doctors tend to underestimate the side effects the patients experience, and of course doctors want to do best by their patients in terms of preventing the cancer from coming back.

We recently did a very small survey, this was done in preparation for a working meeting we had where we brought 10 breast cancer advocates together, and we asked them about what amount of benefit they would be willing to give up in order not to receive certain treatments. Pretty much as we expected, depending on the treatment it was anywhere from the range of a few percent benefit to a little more that they'd be willing to give up. But people aren't willing to give up big benefits. If we think that the benefit is substantial, people very much want to take the treatments.

Chris Riback: Yes, I would think so. I can kind of think about that balance. In thinking about this work, I also found myself thinking about our discussion as a society on healthcare generally and the American approach to healthcare. So maybe if I'm extrapolating too much from your work then you'll reel me back, but I feel like this type of work has the potential to have an impact on the overall healthcare discussion in our country on how we should think about it, how we should approach it, on how we should think about that balance of too much treatment versus quality of life, but wanting to do everything because who wouldn't want to do everything possible for their loved one or for themselves. Do you see that? Or am I going too far?

Dr. Eric Winer: No, I see it. I think the one thing we have to be careful about is that we have to decouple this from any issues related to economics.

Chris Riback: Yes.

Dr. Eric Winer: So the reason we're trying to back off is not to save money. That is something that has to be decided at a societal level. You know, in some countries, for example the UK, there have been decisions made about treatments because they just don't feel that on a societal level it's worth spending this amount of money for cancer compared to spending the money for vaccination or other such things. I don't think we should be talking about the economics at all.

But I do think we should be talking about quality of life issues, and I think that, again, when we do these de-escalation trials, the places we usually start are in people who have a very favorable prognosis, so there's not a lot of benefit to be given up, or in people who for one reason or another can't tolerate a standard treatment, so we're taking advantage of the fact that they can't tolerate a standard treatment anyway to see how a less intensive treatment might fare.

But you know, there are complex psychological issues, as we've touched on, for both patients and doctors. There are funding issues in terms of these trials. Then the other issue that people may not appreciate is that there are very complex statistical issues around some of these de-escalation trials that make some of them, like the TAILORx study, absolutely huge studies, and there are only so many of them that we can do.

Chris Riback: Understood. Well, we will stand by and see how the rest of this, I guess pretrial works and what ends up being next on the broader research. To close out, you've been a BCRF researcher since 2003, you're on the Scientific Advisory Board of it. As the saying goes, you are all in. Why? What attracted you to BCRF, and what has inspired you to get even more engaged over the years?

Dr. Eric Winer: Well, the BCRF has been extraordinarily generous in funding both to us and to researchers around the world. The BCRF is all about breast cancer research. They don't try to be about anything other than breast cancer research, and they understand that progress in breast cancer is absolutely dependent upon research. If we didn't have all the research that's been done over the past 30 and 40 and 50 years, we'd be in the same place we were then. You can't make advances by trail and error. You have to conduct rigorous research.

The BCRF has been amazing in terms of its ability to raise funds and then distribute them nationally, internationally, and across an incredibly broad array of researchers, recognizing that it's truly going to take a village, a village of very different types of scientists and clinicians, to solve the problem. So I mean, you know, it's often said, "Has someone drunk the Kool-Aid?" In this case, I've drunk the Kool-Aid in terms of the BCRF, but it's not very hard to drink it. The BCRF is just phenomenal, and I can't say enough.

Chris Riback: It appears to me that you not only drink the Kool-Aid but at this point you also are mixing it, you are handing it out to others, and you're really showing the way. Thank you. Thank you for your time and, more importantly of course, thank you for the work that you have done and continue to do.

Dr. Eric Winer: Thanks for talking, and thanks all who will listen to this for having heard a little bit about our research and a little bit about me and have a good afternoon.

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

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