Hereditary predisposition to breast cancer – a person’s own genes, passed down from parent to child – remains one of the biggest challenges – and opportunities – in the drive to prevent the disease. Of course, women with mutations in the hereditary breast cancer genes, BRCA1 and BRCA2, have much higher risks of breast and ovarian cancers that often develop early in life. That’s why fully understanding the process that a normal cell must take to transform into a tumor cell in BRCA mutation carriers is – among the wide range of important and potentially life saving scientific research – central not only to new insights and approaches to cancer prevention but also, quite simply, how many families may think about their futures. One of the leaders of that research: Dr. Judy Garber. Dr. Garber is Chairman of the BCRF Scientific Advisory Board. She is also Director of the Center for Cancer Genetics and Prevention at the Susan Smith Center for Women's Cancers at the Dana-Farber Cancer Institute, as well as Director of the Cancer Risk and Prevention Clinic at the Brigham and Women’s Hospital. A professor of Medicine at Harvard Medical School, among her many honors, in 2013 Dr. Garber was elected to the prestigious Institute of Medicine, now known as the Health and Medicine Division of the National Academies of Sciences.
Chris: I’m Chris Riback. This is BCRF conversations, our series focusing on scientists, thinkers and leaders who drive the insights and breakthroughs of breast cancer research.
Hereditary predisposition to breast cancer, a person's own genes passed down from parent to child remains one of the biggest challenges and opportunities in the drive to prevent the disease.
Of course women with mutations in the hereditary breast cancer genes, BRCA1 and BRCA2 have much higher risks of breast and ovarian cancers that often develop early in life. That's why fully understanding the process that a normal cell must take to transform into a tumor cell in BRCA mutation carriers is among the wide range of important and potentially lifesaving scientific research. Central not only to new insights and approaches to cancer prevention, but also quite simply how many families may think about their futures.
One of the leaders of that research, Dr. Judy Garber. Dr. Garber is Chairman of the BCRF Scientific Advisory Board. She is also Director of the Center for Cancer Genetics and Prevention at the Susan Smith Center for Women's Cancers at the Dana-Farber Cancer Institute as well as Director of the Cancer Risk and Prevention Clinic at the Brigham and Women's Hospital. A professor of medicine at Harvard Medical School among her many honors in 2013, Dr. Garber was elected to the prestigious Institute of Medicine, now known as the Health and Medicine Division of the National Academies of Sciences.
Dr. Garber thanks for joining me. This concept that someone might have inherited a predisposition to any disease, and not just breast cancer, it surely brings up all sorts of conflicting feelings on all sides of that human relationship. I assume that that central role must play a big part in why you've made hereditary predisposition such an important and driving part of your life's work.
Dr. Garber: I think so. It's a lot of syllables. People are observant and they recognize that some diseases, and certainly breast cancer is something that seems to cluster in families. That’s really all inherited predisposition symbolizes because you wonder why should a cancer cluster among family members, and you wonder if there's not some inherited reason for it. That’s really all that inherited susceptibility is.
Chris: You are in the process of conducting major research on both sides, let's say, if the cancer problem, the prevention and treatment. You've done and are doing important work as noted in the BRCA genes but you're also doing work on the treatment side and looking at the relative effectiveness of cisplatin and standard chemotherapy in women with early stage breast cancer who've inherited BRCA mutations.
I want to ask you of course about the research itself, but first working on those two sides, both the prevention and the treatment side, how do they connect for you and how do they connect in your research? Or do you somehow ... Are they separate entities or is there a continuum as you think about this overall issue that you've dedicated your life to?
Dr. Garber: Well certainly they are connected. I think when this all began 20 years ago, we had this same observation that in some families there was more breast cancer than one would expect and certainly that younger women were affected. Then Steve Narod and others began to report about families where both breast and ovarian cancer occurred.
When the genes came with the work of Mary-Claire King and others, then suddenly you could within a family distinguish those women who had real risk of breast and ovarian cancers and those who had the family history but did not share the risk. Once you could identify those people whose risk was so much more elevated than the general population, of course you want to try and prevent cancer. That's really the main goal to make it so that having these genes tells you what you have to do, but still that not getting cancer is where you want to be.
Unfortunately, it doesn't always work that way. Often women that we're in the process of helping through figuring out their risk or figuring out what to do or women who didn't realize that they had perhaps features that might have made them likely to have an altered gene that gave them more risk developing cancer. Then the question is should they be treated like everyone else?
The more we learned about what BRCA1 and BRCA2 and increasingly other genes did and that their role was really important in making sure that cells could repair errors in their DNA when they occurred in their genes that happen all the time. We're always making errors and we have complicated systems to fix them and BRCA1 and BRCA2 are very important in those systems.
Once you knew that, then you could start to think well is there a way to exploit that vulnerability that having a mutation in these genes would give you in a tumor that developed in that setting? Now that was an incredibly long sentence, and I really apologize. If you understand what genes do, and of course only research can tell you that, then you can think about exploiting that for treatment, and that's what we did.
Chris: That's all. It was that simple. That evaluation of risk, that's got to be such a challenging part of any person's journey. How do you think about that evaluation of risk and as you talk with women who may have various predispositions, but that doesn't necessarily mean that they're going in any particular direction? How do you guide people in terms of considering those risks? Is it just learn as much as you can? Talk to ... How do you help people think about that spectrum of risk?
Dr. Garber: I think that's a very good way to put it, the spectrum of risk. Risk is a ... Really it’s all probability and of course most of us are not that mathematical. We're used to thinking of probability maybe as high medium and low risk. In the setting of the genes, it’s possible to think about risk in short intervals a year or two or in long intervals like a decade or a lifetime.
Many people funded by the Breast Cancer Research Foundation work on these issues of trying to more precisely estimate the risk of cancers associated with these mutations so that whenever in your life you find that you have one, your decisions about how to manage that risk, how to reduce it, how to deal with it are going to be affected by everything else that's going on.
We hope that younger women will be able to still have their babies and use their ovaries for that and nurse their babies. Use their breast for that and all of the normal things that you do and then take on the issue of managing risk. We also need to identify those women whose risk might be higher even before we would like it to be so we can intervene at the right moment.
I don't know if that's really what you were asking, but I think we try to help women find a context for their risk in their own lives so they can manage that risk as part of their lives; not as the focus of their life.
Chris: That’s such a clear a way to consider it. Really I guess it really is all about context and context in itself is such a complicated idea. There’s so many different layers to it, the context of one's family, the context of one's history. Current family, future family, hopes, where you are in life. Everything context is so highly personal.
You’re right, it doesn't seem to me that we all approach every choice and every risk in our lives in a purely mathematical way. There's a lot going on and that's the spectrum I would agree.
You mentioned a moment ago the Breast Cancer Research Foundation that the scientists and the researchers and obviously in your perch as scientific director you have incredible ... You get to see a lot. You really ...
Dr. Garber: I do.
Chris: Yeah, you get to. You love all of your children equally I know. I don't even need to ask you that, but anything that you are seeing or are there trends ... Again, I don't want to ... If there's something in particular that's exciting you that you want to talk about, that's terrific. If you also equally don't want to single any particular piece of research out of there. Are there trends around breast cancer research that are particularly exciting you or interesting you? Then afterwards you can get into the research that you're doing as well of course.
Dr. Garber: Well it's an amazing question. There's so much going on in science these days and Breast Cancer Research Foundation investigators are right in the thick of it leading the charge. I think you have to give credit to the basic scientists. They toil away, and every so often they come up with some insights that just is that aha experience and explain something that goes on. Suddenly you can make a leap forward in treatment. Maybe HER2 was one of those things now more than a decade ago.
Maybe immunology is that now where we can try to exploit the immune system itself to try to help remove tumor that began as self, but the immune system ... We’re all excited about finally figuring out how to harness it and direct it toward the tumor instead of the patient.
We have so many more tools. We have amazing what we call bioinformatics. Really people who sit at the edge of mathematics and computer science and can take large datasets of genetic information or other molecular information about tumors and find completely new ways to look at tumors and tumor behavior that give you possibilities for treatment that you would not have thought about just a year before. It moves so fast today.
It requires generally collaboration because you find something you're not sure what it might mean. You have to ask someone who might have seen it before, and the next thing you know, you're collaborating. It's a different time.
Chris: Is that part of your role when you think about acting as scientific director and the connecting of ... You see so much from where you sit. I imagine, I've got this this vision of that papers and emails and research and ideas. Just there’s constant almost Twitter feed, if you will, of information that you must be privy to. Is connecting and helping folks connect those dots, is that part of what you do or what you enjoy doing? Or is it more people ...
Dr. Garber: That would be a very interesting way to spend your time I think, but probably I’m not smart enough for that. I think people find their way together, and the nice thing about the BCRF is that it does bring scientists together once a year in October at a meeting where you get to hear some highlights of what's going on. You can find people that you've only read about who might be working on something you know.
All of us have access to the grants and the publications of the other more than 200 scientists all focused on breast cancer. Most of them eating, sleeping, talking breast cancer all the time. We're not that exciting to anybody else, but to each other, we are an amazing group. I wish I could be a matchmaker, but I would have to say that that is where you provide the fertile soil and people find a way to plant the seeds together, to take the metaphor to the end.
Chris: Got it. Let's talk about some of the seeds that you’re planting and your work on the BRCA genes may be helping discover information about the early steps that a normal cell must take to transform into the tumor cell in the BRCA mutation carriers. What are you finding? Where are you in that research? What are your next steps?
Dr. Garber: Well I'm not a basic scientist, but I have had the privilege of collaborating with David Livingston, Alan D'Andrea both scientists here at Dana-Farber, both funded by the BCRF where sometimes I can provide clinical samples from patients who are willing. They can perform analyses that help work out either very basic mechanisms that BRCA1 or 2 used to do their job or ways that they don't work in tumors that can be targeted by different therapies.
I wish I could say I figured them out, but I'm part of those teams that figure them out. Then my job is to take those observations from the laboratory back to the patients and see in clinical trials whether these things that we predict would make a difference or that seem to work in the mice actually work in humans.
Chris: Understood there's the team and different folks who help drive different areas of the overall research. What's the next stage? Where are you on this and what's the next stage for you guys?
Dr. Garber: Well I’d say we have two different areas of work. One is in the treatment arena for our patients with breast cancers in the context of their genetic alterations. The question is now there's platinum. There are these new PARP inhibitors. There are combinations of drug. Questions are whether you can combine them with strategies like immunotherapy and really find the best way to treat tumors.
Now much of this work at this time is still going on in women whose disease has recurred. It’s come back and is now metastatic or has spread. Also, we're part of a trial that is for women who have been diagnosed when you have the best chance of cure and adding these drugs as part of treatment at that time. We do cure breast cancer patients. We want to cure more of them, and we need to see whether we can do that by giving some of these drugs earlier. Of course they have side effects. We do have to monitor that.
Then on the other end, we are working to try to find the very earliest transformed cells or the earliest evidence that cells show that something has happened related to their BRCA gene or put them on the earliest steps toward cancer to see if we can intervene and stop that process and get rid of those abnormal cells however few they are, and nip that cancer in the bud so that it never really never becomes a cancer.
Chris: Why research for you, and in reading about you and preparing for the conversation that it seems it was during medical school, and in particular in an early research role that you had at the National Cancer Institute that got you interested in family cancer patterns. We discussed those earlier in this conversation.
Was there an aha? You talked to earlier as well about potential aha moments. Was that an aha moment for you that research was a way if all of us are perhaps looking for our own ways to contribute and make a difference and leave the campsite better than it was when we arrived? Was that the period for you? Why research for you?
Dr. Garber: Why genetics? Probably because my own family was affected by breast cancer, and I always expected that we must have a gene, which I guess we haven't found. I began ... In medical training, you're exposed to researchers all the time. At some point you recognize that you can have a bigger impact with research than by patient care alone. I haven't wanted to give up patient care. I haven't had to do that, and I've learned that you can partner with patients to bring research into their lives too and make them part of those victories.
When did that really happen? I guess in medical school you began to see this. For me, it was really in residency training and just afterwards when I came to work with my mentor Frederick Li who just passed away last year. Fred was a real innovator. He looked at families and pattern. He could see the patterns. He knew the genes would be there and he was in research to find the genes.
When I came along, suddenly we realized if there were genes for these rare childhood syndromes, there might be genes as well for breast cancer, for ovarian cancer, the more common cancers. We set out to work with groups to find them. Seeing that you could suddenly help a family make sense of their history because of research made research something that you wanted to do.
Chris: It makes it real and tangible and humanly ... Yes I can understand that how you ... In fact I’m also struck just listening to that. How much of science ... It appeared to a lay person like myself, it would seem as such a straightforward way of thinking. Yet it seems to apply to so much when I talk to scientists and researchers that you saw something or thought of something in one area how there may be genes for certain childhood diseases. You think, well, gosh if it's happening over here, maybe it's happening over here as well, around breast cancer. Is that what [inaudible 00:19:16]?
Dr. Garber: Yes I think science is not linear. Yes you may have an idea and follow it all the way forward. Suddenly you have to veer to the left or veer to the right or jump over something. These are terrible analogies, but the exciting things about science are when you make an insight because you connected two things that you didn't think were connected before, and suddenly a whole new path opens up.
Science is it’s discovery. That's exciting. It’s interpretation of the world around you. That's exciting, and it's making progress. I think all of us who do research, we want to change the world in a different way, and research allows you to do that.
I'm an oncologist just and I've been taking care of patients now for a long time. I think everything I do is for patients today, everything I can do is because of research. That's amazing. It's not like the old days when you gave him whatever you had and hoped for the best. It's not like that anymore. It's completely different and research has transformed oncology. Not only oncology, but that's what I know best.
Chris: Of course it is, and just to close out and to move from what you were just saying on looking back and the changes that have occurred and then looking forward for you. I was struck again by something else that you had said as I was reading and in preparing for this conversation. You said a lot of things that are striking. You were asked, and it was a pretty simple question, how close are we to preventing and curing all forms of breast cancer?
I guess I was expecting almost a clinical or a tie ... Something that this time horizon or something. Your response was although we have succeeded in often making breast cancer a disease that can be cured or managed over a very long time, for every woman who gets breast cancer and isn't cured, that's just not enough. I thought about motivation and inspiration for and just in the most basic way what keeps you going.
Is that it that it's just not enough that what we have done, what folks have done, are doing is incredible? Just of course, but for every woman who isn't cured or person who isn't cured, that's just not enough. Is that the motivation?
Dr. Garber: Yes I think that's exactly the motivation. We've made great progress in breast cancer. We have people today who would never have been alive 15 years ago with the treatments that we had. We can do much more and we can keep people alive longer. I lose patients to breast cancer every day. For those patients, we must do more and for their children since some of those children will get breast cancer too from their genes, some for other reasons we haven't figured out.
We must do better and that is really what the Breast Cancer Research Foundation is dedicated to eliminating breast cancer. Which I totally appreciate because it's not just curing it; it’s also preventing it.
Chris: Dr. Judy Garber, chair of the BCRF Scientific Advisory Board, also Director of the Center for Cancer Genetics and Prevention at the Susan Smith Center for Women's Cancers at the Dana-Farber Cancer Institute and Director of Cancer Risk and Prevention Clinic at the Brigham and Women's Hospital and so much more I guess I could, but should not keep on going. There are a lot of honors and roles. Dr. Garber, thank you so much for your time. I'm Chris Riback. This is BCRF conversations.