Since the BRCA1/2 gene mutations were first discovered in the 1990s, research has made it possible to screen for those mutations and empower high-risk individuals to take steps to reduce their risk of breast and other BRCA1/2-associated cancers—transforming prevention. Today, this genetic information is even being used in the clinic: Drugs called PARP inhibitors are approved to treat cancers that are associated with BRCA1/2.

Despite these incredible advances, BCRF investigator Dr. Susan Domchek says there are still tremendous barriers to lifesaving genetic testing and many patients who slip through cracks in the system. To ensure that everyone who should be screened is, we’ll need a multi-pronged approach. And that’s where Dr. Domchek’s research comes in.

A member of BCRF’s Scientific Advisory Board and an investigator since 2007, Dr. Domchek is the Basser Professor in Oncology at the Perelman School of Medicine of the University of Pennsylvania and serves as executive director of the Basser Center for BRCA at the Abramson Cancer Center. She has authored or co-authored more than 350 articles appearing in scholarly journals, and she serves on a number of editorial review boards.

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Chris Riback: Dr. Domchek, thank you for joining me. I appreciate your time.

Dr. Susan Domchek: Thank you so much for having me.

Chris Riback: So, if you forgive me, I have a bit of a buildup to the core aspect of your work and the solutions you are driving toward. So to begin, it is correct that men and women with a BRCA gene mutation have an increased risk of developing cancers, including ovarian, breast, prostate, and pancreatic, correct?

Dr. Susan Domchek: That’s correct. BRCA1 and BRCA2 mutations affect both men and women. And if you lined up all the individuals with BRCA1 and 2 mutations in the world, half would be men. So oftentimes, we forget about men in this equation, but there are increased cancer risks to them as well.

Chris Riback: Great. And the testing and genetic testing not only exists, but that testing has served as a model for how to use inherited generic information to guide clinical care, correct?

Dr. Susan Domchek: Absolutely. When we first learned about BRCA1 and BRCA2, which was back in the 1990s, we knew that these genes were associated with cancer risk, but we didn’t really know what to do with that information. And over the past now almost 30 years, we’ve figured out what those risks are, how to screen for those cancers, and [how to] reduce the risk of those cancers developing. And most importantly, in the last 10 years or so, how to use drugs to specifically target cancers that develop in the setting of a BRCA1 or BRCA2 mutation. And that latter part is incredibly exciting, and, I would argue, somewhat unanticipated and demonstrates the value of basic science and how to translate that into clinical practice.

Chris Riback: And so then, getting to the core or one of the cores of your work, the challenge, why have so many individuals who carry BRCA mutations not undergone genetic testing? Talk to me about those barriers.

Dr. Susan Domchek: It’s a really great point, and I think it’s multifactorial. The first is that people aren’t necessarily aware of this issue and the fact that cancers can be genetic, but I’m not putting this all on individuals and patients. Providers, physicians, nurse practitioners, nurses need to be aware of this and identify those individuals who are good candidates for genetic testing and then, get it done. So the first barrier is just identifying people who are good candidates for genetic testing. The second barrier is the genetic testing itself.

So when we first started all this a number of years ago, there was a very kind of protracted model, where individuals would come in, meet with a genetic counselor, they might come in a second time before their blood drawn, and then, they’d come in a third time to get their results. So this was putting a lot of barriers on patients, just in terms of getting into clinic multiple times, the time that it took to do so. And we’ve been streamlining over the years, making that a simpler process, but it just needs to be simpler even than it is already. So we need new models for genetic testing that can incorporate different needs of different patients. And what do I mean by that?

Chris Riback: Yes.

Dr. Susan Domchek: Well, if you’re an individual who has advanced pancreatic cancer and you’re trying to get this information to know whether or not you are eligible for a specific drug, we need to get that information quickly, and we don’t want to have sort of unnecessary barriers. And so, one of the things that we developed is just a simple video intervention, where people watch a seven-minute video and then, we test that individual right there and right then. And that has massively increased our ability to get individuals with pancreatic cancer and metastatic prostate cancer to get genetic testing, so that they can get the drugs that they need. And this is work that’s been funded by BCRF, and we have made this information sort of available on websites, the videos, and sort of the process by which you can sort of streamline that testing. So that’s just one example of how to decrease barriers, but there are many others that we are working on.

Chris Riback: And to make sure I’m understanding your point, I think of genetic testing as a preventative measure. Understand, “Do I have genetic markers? Does someone have a genetic marker for a particular form of cancer?” What you just indicated though is that the genetic testing also can be used to help identify the appropriate drugs that an individual might need.

Dr. Susan Domchek: Absolutely. And this is a really important point, and one that’s really taken hold over the past five or so years is that we have drugs called PARP inhibitors, that are FDA approved to treat cancers that are associated with BRCA1 and 2 for breast cancer, ovarian cancer, pancreatic cancer, and metastatic prostate cancer. So these drugs are really, really important. They are pills, they are not chemotherapy, and they can really lead to an improvement in quality of life in early-stage breast cancer that’s high risk. We’ve shown that PARP inhibitors given for a year, a specific drug called olaparib [Lynparza®], can decrease the chances that the cancer will return outside the breast, so decrease the chances of developing metastatic breast cancer. And also, improve survival for a woman.

So this is really, really important information. These drugs can improve survival in breast cancer and, likely, ovarian cancer. The data there are very significant, in terms of decreasing the risk of cancer coming back, so we need to quickly get this information into the hands of patients with active cancer. And at the same time, your point is well-taken. In individuals who’ve never had cancer, this information can be lifesaving, in terms of knowing that you’re at risk for cancer and taking the appropriate measures to either detect it early or to reduce the risk of developing it all together.

Chris Riback: And showing the video, informing the patient, or helping inform, or helping educate the patient at that location, is that your point of care study, the POC study?

Dr. Susan Domchek: Yes. Yes. Sorry to interrupt. That’s exactly right. And there are many ways to do this, but I think that the important thing is that we’ve shown and sort of published that this is an efficient potential option. And I want to be clear that I think that there’s many different ways that genetic testing could be done and what we call pretest education could be done. And I don’t think there’s a one-size-fits-all approach here. Some people have called this eating the elephant. You can eat different parts of the elephant in different ways, as long as you try to eat the whole elephant. We need to be nimble, we need to realize that different patients need different things at different times, but we really need to keep at it.

And we need to say to ourselves the question you started with: “Why aren’t people who should be getting tested getting tested? What are those barriers?” And one thing that we haven’t discussed yet is that there are significant disparities in genetic testing. Individuals who are Black or of lower socioeconomic status are much less likely to get genetic testing, as are individuals of Latino ancestry. And so, it’s really important that we recognize that these disparities exist and that everything that we do tries to decrease those disparities.

Chris Riback: Well, that segues to an article that I found on you, a conversation, an interview that you did a couple years ago that I wanted to ask you about, but you’ve led into it very well right now. This was an interview that you did with your colleague, Dr. [Carmen] Guerra. This may be 6, 7, 8 years ago. And Dr. Guerra was asked, “Are you seeing change now, in terms of more Latinx women getting tested?” This was a piece that you were talking about a number of challenges around genetic testing, but among them, ethnic background, socioeconomic class, issues like race, issues like that. And when Dr. Guerra was asked, “Are you seeing change now, in terms of more Latinx women getting tested? How can we achieve progress faster?” I don’t know, do you happen to remember her answer in that article?

Dr. Susan Domchek: Yes. I don’t remember precisely, but I know we were closely together. And this is, I think we’ve made progress in some areas. So just to give you some examples, at least at Penn, our success rate in testing, for instance, ovarian cancer patients, we now test more than 90 percent of all of our ovarian cancer patients. That number should be a hundred. Right now, it’s 94 percent. So we’ve definitely gotten much better. Pancreatic, we’re doing very well. Metastatic prostate cancer, we’re doing a little less well. So we have to iterate over and over again and look at the data and say, “Are we closing that gap?” And the area that we’re really working at on right now is those individuals who don’t have a personal history of cancer, but have a family history of cancer. And so, we’ve been initiating some strategies in different clinics at Penn that have different patient populations.

One is suburban, one is inner city, and really trying to say, “Okay, these are different strategies that we can take. We can do nudges through the portals. We can do text messages. We can do physician nudges.” So my point is that we have to continue to iterate. We can’t just let it go. At the same time, we do outreach and education to community health organizations, at community fairs. No, this is a multifactorial approach, but physician education is really important. It shouldn’t be up to a patient to recognize that they’re at risk.

Chris Riback: I’ve got to say, Dr. Domchek, that response certainly verifies Dr. Guerra’s answer to that question. So the question was, “Do we want to achieve progress faster?” And Dr. Guerra’s response was [that] we are seeing change, but probably not fast enough for Dr. Domchek. How important is, I think I know the why, but impatience is important for somebody in your role, isn’t it?

Dr. Susan Domchek: Yes. I’m actually getting a little bit teared up right now, because even just this week, and I saw two patients who didn’t know about their genetic testing, and therefore, were diagnosed with advanced cancers. And every single time that happens, it feels we’ve lost an opportunity and we’ve let that person down. So it’s always a challenge, because right now, we are not testing the people at the highest risk. There are certainly arguments out there, that you should just test everyone in the country. But from an implementation standpoint about how you get that done, right now, we’re not even picking the lowest-hanging fruit. We are not testing the people that have significant family histories. So we’ve just got to keep working at it. And we’ve got to keep trying everything that we can do from all angles to get more of this done. And again, there’s lots of people working on this throughout the country, and there is a sense of this virtuous impatience, if you will, to really try to make a difference.

Chris Riback: You were talking about the two patients. What a statement that you feel that “we let them down,” that it becomes that personal, huh?

Dr. Susan Domchek: Yes, in the end of the day, I’m a practicing medical oncologist, and it never gets any easier, when we significantly disrupt people’s lives. Even if we are able to successfully treat their cancers, it is not a fun process to undergo treatment for cancer. And so, all of these things play a huge role. And obviously, we don’t always successfully treat people’s cancers. That isn’t to say that we can prevent all cancers or any of that stuff, but we definitely can do a better job than we are currently doing. And we are also very hopeful that we can use genetic information in different ways and that we can develop better risk reducing strategies beyond surgery. So at the same time as we’re trying to just like, let’s get the right people tested, so that we can give them options to reduce their risks, we are, at the same time, trying to come up with better options, so that we have non-surgical prevention options for patients. We’re not there yet, but we are really working on it.

Chris Riback: What is the role of commercial genetic testing? I read, and I don’t know enough, so you’ll kindly explain it to the extent that it’s important for us to understand, but there’s the genetic testing core within the electronic medical record system, and I guess that that’s called the precision medicine tab, but it connects, I believe, with commercial genetic testing. What role or potential role does that have in all of this?

Dr. Susan Domchek: So most germline genetic testing, so testing for things that you are born with, inherited genetic mutations, is done through commercial third party labs, if you will. Most individual hospitals, that are academic sites, do not do their own genetic testing. There are exceptions, but the vast majority of genetic testing in this country happen through commercial laboratories. But what we did at Penn, and this was a huge effort, at Penn, my colleague, [BCRF investigator] Dr. Katherine Nathanson, was integral in all of this, is make it easier to do ordering.

Because I know this sounds ridiculously old school, but in the past, you would have to go to an individual’s lab’s portal, you would have to enter the information into that portal, and then, the information would come back as a PDF document, which would then be scanned into the medical record as something helpful, like lab test, which nobody could ever find again. Because it was just lost in the medical record. So these strategies that we’ve taken, which might seem so obvious, have been really critically important for us to be able to measure and monitor what we’re doing. So we are now able to order directly through the medical record to this lab, and then the information comes back as a discreet field into the medical record, which means that people can find it and also that you can develop what we call clinical decision support tools, which are launched by Epic is the electronic health record that we use.

And it’s used by a large number of sites in the US. I think it’s about 50 percent. And that enables us to trigger things like, “Oh, somebody’s overdue for a breast MRI.” So all of these pieces, you can see how all these pieces would be important, but for the purposes of what we’ve been working on with BCRF, it also allows us to pull out from the electronic medical record, “Oh, this person should get genetic testing. Did they?” And I know that sounds silly, but in the past, we couldn’t really tell, unless you went into the chart and clicked open all these individual PDF documents. So you can’t monitor what you can’t measure. So now we can measure, so we can monitor.

Chris Riback: Listening to you, it’s reminding me of something a friend of mine told me about, in terms of a totally different circumstance, a kid getting into school. And I asked, “What do you think did it? What do you think got your child in?” And his answer was, “Everything.” Meaning, there wasn’t any single thing. There’s no way one could ever identify would it be one single thing. It’s that, if you want to get to a goal, you have to do everything. And in listening to you, that’s the relentlessness, I called it, impatience, Dr. Guerra did. But that sense within you that it’s everything.

It’s education at the point of service, when the patient is at your office. It’s other types of education. It’s getting involved and helping educate and energize, as it were, the primary care physicians. It’s even down to the detail of, “How do we integrate with electronic records with third party companies?” Something that one would think, “Oh, how could an oncologist, somebody in your role, how could you be worrying about integrating with third party electronic records? That’s got to be somebody else’s problem.” And no, your mind is on everything. Am I interpreting you correctly?

Dr. Susan Domchek: Yes. And it establishes the role of collaborative efforts. Because in order to do all this, you need things like an information technology department that is willing to take this on, which they were, and they did. But it really is, as you said, it’s all the pieces. And if you had asked me, 10 years ago, that I would be sort of sitting here concerned about how things integrate in the electronic health record, I’d be like, “Oh, that’s not my job.” But it is your job when it becomes a valuable tool to achieve the goal. We have a new president at Penn, and she calls this “virtuous impatience,” which I think is a very interesting phrase.

But it is sort of, as you said, you have to educate patients, you have to educate providers, you have to make it easier for people. You have to be able to find the results. You have to be able to act on the results. If you want to make a difference, all those things have to be true. You have to get people genetic testing, and then, you have to act on that information. And you have to take them all the way through the process. It doesn’t help to just sort of know that this information could be useful. You actually have to do all those pieces of it.

Chris Riback: Tell me about you. How did you get to this type of role? And going way back and growing up, was it always science for you? Were there other plans, but science derailed them? How did you get to here?

Dr. Susan Domchek: Well, my father is an engineer, and my mother is a nurse. And so, I started off as an engineer in college, but then did research and realized that I didn’t want to be in the basement of the hospital, I wanted to be upstairs. So that’s how I got to medical school. And I graduated from medical school in 1995. BRCA1 was cloned in 1994. BRCA2 was cloned in 1995. So I sort of grew up with this as this incredible breakthrough. And did my internship at residency at Mass General, and then, my fellowship at Dana-Farber Cancer Institute, where I trained under Dr. Judy Garber, our scientific director at BCRF. And it was at that time where we were really starting to understand how to use this information about BRCA1 and BRCA2.

And then, my husband and I moved to Penn in 2001, and I was fortunate to then take over the program, the genetics program there. So I have been incredibly fortunate to have opportunities in my career and excellent training. But I also feel like I was at this incredible time in science where we were just figuring out these genes. And then the idea that these could be targeted therapeutically is, and I’ll explain why that’s so kind of hard for scientists, I think, at least me, to get my mind around, which is it’s much more straightforward to target things that are turned on. So the estrogen receptor, HER2/neu, these things are on, and we turn them off when we target them therapeutically. But BRCA1 related cancers, the protein is lost. There’s no expression of the protein.

So how do you target something that’s turned off? And this is where brilliant scientists, basic scientists, [BCRF investigator] Dr. Alan Ashworth and others, figured out how to do that by targeting it in a way that’s called synthetic lethality, which is, if one pathway is turned off, the cell can survive. If a different pathway is turned off, the cell can survive. But if you target both pathways at the same time, the cell dies. Sometimes people have used the analogy of, if you have a chair, you can balance on three legs, but you can’t balance on two. It’s kind of a simplistic way to think about it. But nonetheless, this led to the development of drugs, which, of course, so many people were involved in this, it was such an exciting time. And the idea that we got, from this time in 1995, of just not even really knowing what these genes did in the cell to, by 2014, an approval for PARP inhibitors and now, data that we can improve survival using olaparib in early-stage breast cancer. Well, just that story, that narrative, scientific narrative, involving thousands of scientists is really an exceptional story.

Chris Riback: Yes, the fact that you came in at the first chapter, or maybe even the prologue, what an incredible time to have entered the field. And yes, it’s understandable why that would help inspire you to exit the basement of the hospital and spend your time on the front lines. On that point, and to close out, BCRF, you’ve been an investigator, BCRF investigator, since 2007, you’re a member of the Scientific Advisory Board. What is the role that they’ve been able to play, not only, I guess, in your work, but in your life?

Dr. Susan Domchek: BCRF is an incredible organization. It provides funding for an investigator, with flexibility, with the ability of that investigator to pivot when they recognize an opportunity to use those funds in a more strategic and, if you will, impatient manner. Science sometimes you work on a project and you get a little stuck, it’s not going in the direction that you want it to. Some traditional grant funding opportunities, you have to work your way through aim one, aim two, aim three. BCRF, you might finish the work that you’re doing more quickly, and then, you can pivot, you can go to the next exciting chapter. That flexibility is just really unprecedented and remarkable. And if you talk to BRCF investigators, you’ll hear this over and over again. It allowed them to tackle exciting new projects quickly.

And I think that that’s a really important component. I collaborate with so many investigators throughout BCRF, and sometimes science, people say, “Oh, you all don’t talk to each other. You don’t collaborate.” Well, they don’t see how we work within the context of BCRF. A little healthy competition is always a good thing, by the way. And that is always a good thing. But, so BCRF has meant that my career was successful. If I hadn’t had that early BCRF funding, I really don’t think that I would be where I am today.

Chris Riback: It’s wonderful to hear, and you’ve verified my three conceptions, because I was really looking forward to the conversation. The last thing I’ll say is, another article that I found and read about you a little bit was a piece, this was more recent, it was just last October, and it was about the possibility of cancer vaccines. It was the New York Times piece. After giving up hope on cancer vaccines, doctors start to find hope. And you were quoted very near the top of the piece, and your quote was, or one of your quotes was, “‘It’s super aspirational, but you’ve got to think big, ‘ Dr. Domchek said.” And that’s the sense that I’ve gotten in this conversation with you. You’re not afraid to think big. Thank you for that. And thank you for the work that you do by thinking the way that you’ve described, by thinking big. Thank you.

Dr. Susan Domchek: Well, thank you, Chris. And again, it’s always a pleasure. And BCRF will always be close to my heart. So I’ve been honored to be part of this organization.

Despite their tremendous potential, advancements in medicine don’t reach all communities equally. This reality is complicated by social, personal, and informational barriers. Why are Black women 40 percent more likely to die from breast cancer than white women? And why is it such a challenge to make clinical trials reflect everyone who faces breast cancer?

That’s where Dr. Sonya Reid comes in. Dr. Reid and her team are working to address these disparities in breast cancer diagnosis and treatment through research.

Dr. Reid is an assistant professor of hematology/oncology at Vanderbilt University Medical Center. Her three-year Conquer Cancer–BCRF grant was made possible by The Estée Lauder Companies’ Charitable Foundation Awards. Dr. Reid is also focused on improving healthcare delivery to underserved communities and increasing the representation of minority patients in clinical trials. She is actively involved in breast cancer research in Jamaica.

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Chris Riback: Dr. Reid, thank you for joining. I appreciate your time.

Dr. Sonya Reid: Thank you for having me.

Chris Riback: I read a powerful quote where you said, “I’ve always been intrigued and appalled by the significant racial disparities among patients with breast cancer. Black women are more likely to be diagnosed at a younger age with breast cancer. Black women also have more aggressive disease and have worse mortality.” To understand the importance of your Conquer Cancer study, which I really look forward to getting to talk with you about, I think it’s important to first establish the context and the fact that Black women are 40 percent more likely—you correct me if I have that stat wrong—to die from breast cancer, compared to white women. It’s a remarkable starting point. How do you reconcile that statistic?

Dr. Sonya Reid: Yes, it’s disheartening when you think that overall the mortality rate from breast cancer is actually reducing. But then when you look at a certain population of patients, that is Black patients, we see that there is a significantly higher burden of death among that population. And I think that’s just appalling. We know, however, it’s not one thing that’s causing that statistic. It’s definitely complex. We know it ranges from differences in social determinants of health, for example, where people live, how people live, the access to healthcare that patients are able to receive. Where they get their healthcare, we know matter, right, and whether or not they have insurance. We know all that plays into it as well. We also know that tumor biology as well as genomics could potentially have an impact or play a part in what we see as this overall disparate outcomes when it comes to survival among females with breast cancer.

Chris Riback: It’s such a potential mix. I mean, you’re talking about nature versus nurture, genetics versus social inputs. How does that end up getting unwound?

Dr. Sonya Reid: I don’t think we can say it’s one or another, right? I don’t think it’s only nature or it’s only nurture, as you said, right? But what I will say, race is a social construct. Most of the racial disparities that we are seeing in breast cancer and in other types of cancer and in health overall is really based on a lot of societal discrimination that we see when it comes to access to care as well as comorbidities that start from prevention, screening, and all the continuum of care that we see. So that’s the first thing. I always like to frame that: Race is a social construct. And it’s something that I have to even remind myself as a researcher when we start thinking about questions and how we approach a research question from the beginning.

However, we do know that there are certain aspects of breast cancer, for example, even incidence. We know that Black females are more likely to be diagnosed at younger ages. They’re more likely to get triple-negative breast cancer. So we know that there’s some differences inherent in the type of breast cancer that certain patients get versus others. Does that mean that they will have a worse outcome because they’re more likely to have triple-negative breast cancer? I don’t know if we know that answer at this point.

There’s a lot more research that needs to be looked at to say to ourselves, for example, “Triple-negative patient that’s Black, triple-negative patient that’s white, if they receive the same level of care, the same quality care, will these patients have the same outcome?” And I think that’s a lot of what fuels me and a lot of the questions that I’m interested in—really trying to make sure that we don’t blame one or another, but really then drill down to say, yes, there may be differences in biology, but once we appreciate those differences and once we know and understand what’s driving some of those differences, if we understand how to address those differences, can we then level the playing ground to allow those patients to have the same level of care?

Chris Riback: It’s such a fascinating approach for someone like me to hear about from someone like you. You’re a researcher, you’re a scientist. I would think about the genetics. I would think about hearing, how can we get at the heart of the genetic makeup and how could potentially CRISPR be a tool so that we could start to affect the genetic approach going forward? But it’s both, is what I’m hearing from you. It’s, yes, let’s get at that genetic answer, but you’re a scientist, you’re a researcher, you’re not about to ignore the potential social inputs as well.

Dr. Sonya Reid: Absolutely. And I think, as I mentioned the fact that we know race is a social construct and a lot of the data that we have today always does Black versus white, and look at it across Black, white, Asian, other, Hispanic, non-Hispanic, white, et cetera. But what I think we have missed is the opportunity to look at ancestry in a lot of our studies. And I think it has been done now more recently, where we’re really trying to understand, being Black, looking at it from a race standpoint, we know it’s different if you’re from West African ancestry versus East African ancestry, for example. We know that there are differences in incidence and even mortality rates depending on where your ancestry originates. I actually think that’s something that we maybe need to layer on, not just looking at race, but also trying to understand, are there underpinning from an ancestry standpoint that could be contributing to some of these differences we see in incidence as well as mortality rates?

Chris Riback: So you need to be an oncologist, a sociologist, a genealogist, and with some of the locations perhaps that you get to go, a bit of an outdoor explorer as well. I don’t know how –

Dr. Sonya Reid: Yes, a little bit. A little bit.

Chris Riback: Terrific.

Dr. Sonya Reid: It’s complicated, right?

Chris Riback: It’s complicated. But I would assume also that that really keeps it even more interesting and must fuel the curiosity that must drive somebody like you.

Dr. Sonya Reid: Absolutely.

Chris Riback: That’s what I expect. So let’s get, if we can, to the main event. What is your Conquer Cancer study? What questions does it seek to answer? What is your hypothesis? How is the study structured?

Dr. Sonya Reid: Great question. So my Conquer Cancer study, which is funded by BCRF, is essentially trying to understand differences among patients with hereditary breast cancer. So essentially, we’re recruiting patients that have breast cancer and a germline mutation in either BRCA2, BRCA2, PALB2, CHEK2, or ATM. And we are creating this very diverse cohort, which essentially we’re leveraging our partner groups that have more diverse representation of patients to make sure that we have approximately a 20 percent or higher minority enrollment rate was one of our targets that we set out to achieve.

But we’re trying not to only understand the differences across these different mutation carriers, but really trying to understand how that may differ across different race and ethnic groups. So once these patients are enrolled, we will then do tumor profiling. So patients will have DNA and RNA sequencing done on their tumors for us to truly understand even tumor development and how we can perhaps refine treatment in the future for patients with hereditary breast cancer.

Chris Riback: Where are you in the study?

Dr. Sonya Reid: I think we’re more than halfway with enrollment. And I will say we have met our accrual goal when it comes to diversity. So that’s something that we’re super proud about, but of course, still more work to be done. So we continue to partner with our different research collaborators and patient advocacy groups, because we truly want to ensure that we don’t only understand how these differences may be accounting to maybe some of the disparities that we’re seeing in outcome, but truly do a deeper dive as it relates to how does this differ across different ancestry, because that’s another future goal of this endeavor, for us to then look at not just race, but how does that intersect as it relates to ancestry of these patients that are diagnosed with hereditary breast cancer?

Chris Riback: So Dr. Reid, the obvious question that anyone would want to know, what’s next?

Dr. Sonya Reid: So that’s a big question. And I think I alluded to some of that as it relates to the ancestry studies that we will be performing. But another passion of mine is really increasing the diversity in clinical trials. And for example, I’m a part of a pilot study that we’re doing here at Vanderbilt in breast center, where we’re truly trying to engage the community to increase the patients, the diversity of patients that actually come through our doors at Vanderbilt, right? Because we do know that in order to increase diversity in clinical trials, it really matters when we think about the patients that you’re seeing. We know that most patients that get treated for breast cancer actually get treated in the community. About 80 percent are treated in the community, yet most of our clinical trials are in academic centers.

So I think that’s one lens that we need to make sure that more clinical trials are actually in the community where patients are being treated. But as an academic center, which is where I practice, one of my endeavors that I’m working alongside some of my colleagues here to focus on is how can we be patient-facing, have those inputs in the community to increase minority patients that come through our door, and then increase minority patients that get onto clinical trials? Hopefully then this concept would be something that we could roll out across different disease types here.

Chris Riback: Why is it such a challenge to increase the representation of minority patients in clinical trials? Is this a challenge of supply or demand? It would seem to me, sadly, that there’s no shortage of supply.

Dr. Sonya Reid: Right. No, great question. And even with my Conquer Cancer award, it’s embedded in the fact that we’re leveraging different organizations, different patient advocate organizations, as well as different research organizations that we know have more diverse representation, because again, my intentional focus with this study is to make sure we actually over-represent Black patients in this study. And so far, I would say that we’re meeting that target where we have more than the 13 percent Black patients in this study, which is something that we’re super proud of. But again, that takes intentionality. From the get-go, we decided to align ourselves with different groups that we know we could leverage because we truly want to understand, how do these different clinical pathological differences that we’re trying to unravel, how does that look across different racial ethnic groups? Unless we are intentional when we’re starting out different projects, I think we will continue along that cycle where we exclude these groups, if we’re not intentional about included them in our research projects.

Chris Riback: Earlier in the conversation you were discussing that the ways to get at the heart of the role or not role, or the amount of factor or not amount of factor, of race in breast cancer instances and outcomes was you described wanting to understand the genetics and the biology, but then off of that establishment or some level of establishment, then also move into the social components. Does this study help advance you in that first part in terms of the biology of the understanding? And then the other part, how do you connect what we’re talking about right now to the first part of the conversation? Did I interpret that correctly?

Dr. Sonya Reid: Absolutely. So because now we will have this cohort essentially that we expect by the end to be over 200 patients with breast cancer and a germline mutation, we will then be able to sequence their tumors to try to understand from an actual tumor standpoint, looking at the somatic mutation, again, now we’re looking at even tumor development. Does that differ across different racial ethnic groups? And of course, we’re able to understand these things better when we have a representative sample. So we will be able to look at patients’ tumors, of course, we’ll have treatment information, we’ll have clinical information from beginning to survivorship essentially. But one of our future goals is also to be able to look at ancestry, because we would then be able to look at RNA  sequencing data and then leverage that to then look even within this cohort to understand how ancestry impacts some of the differences or similarities that we may see across patients with hereditary breast cancer.

Chris Riback: And I know that maybe it’s a related priority of yours, is improving healthcare delivery to underserved communities. Is that where this leads? Is this a baseline for affecting-

Dr. Sonya Reid: Yes, yes.

Chris Riback: Tell me about that, please.

Dr. Sonya Reid: Yes, because a lot of times we think about hereditary breast cancer, how does one know that they have hereditary breast cancer? If you are not tested, if you are not offered genetic testing, you would not even be a part of this study. And we know that minority patients are not offered genetic testing as they should, for whatever reason. I think that’s a whole other conversation. And we know that once they’re offered and it’s explained that they’re just as willing to want to understand whether or not they have a gene that could change their treatment course.

The bottom line is not only for this study, but to answer your question as to access to care, et cetera, I think we need to really try to make sure that we’re making information available to the community, so community awareness and patient education as it relates to: What is genetic testing? What is hereditary breast cancer? What does that mean? Can that help me? Can that improve my outcome? Answer is yes. But why didn’t I receive testing? And how can I now get it?

So part of our study, and a lot of the groups that I partner with, that’s actually a part of our initiative, to make sure that we are not just educating patients, but once a patient is interested, they actually offer testing for free. We know that we have a group of patients that not only have they not been offered genomic testing from germline to even tumor sequencing, that really changes one’s treatment path, but they’re also not offered clinical trial as equal as their white counterparts.

So I think we need to make sure when we’re tackling that whole thing, when we think about access to quality care, we need to make sure that we understand the reason why this is so critical. Because we now have over the years, have kind of, I would say, maybe even keep widening these disparities. We now have PARP inhibitors, where PARP inhibitors are a treatment for patients that have a germline mutation in BRCA1 or BRCA2 as it relates to breast cancer. So we know that treatment with a PARP inhibitor will improve outcomes, improve survival. These patients will live longer, is what this means, if they know that they have that mutation.

But if a patient doesn’t know that that treatment even exists, because guess what, they were not tested, that patient then don’t get offered it. Now we have an advancement, and the disparity continues to widen. So I always say whenever there’s a treatment advancement and we don’t ensure that all patients, whether rural, urban, Black, white, can get access to that advancement, in this example, a PARP inhibitor, when you have a BRCA1 or 2 mutation, if we’re not able to make sure that that advancement reaches all our patients, we will continue to see widening disparities in breast cancer, unfortunately.

Chris Riback: Well, and that’s just a terrible gap, because now you’re talking about something where there actually is something that could be done where the positive impact on the patient is not being made, not because the cure or the help hasn’t been found. It’s because they don’t know about it, the communication isn’t there, the testing. It also makes me think, you mentioned it very, very quickly, but I know from other conversations how important and deep of a role these partnerships play, because getting to those communities … I assume that you’re in Nashville right now as we’re talking.

Dr. Sonya Reid: Yes.

Chris Riback: But obviously you work at Vanderbilt. You’re not on the ground. You might be on the ground at certain periods, but you’re not on the ground at these locations 24/7. Those partnership relationships are everything, aren’t they?

Dr. Sonya Reid: They are. And these patient advocate groups are our champions. They are the true heroes, because the groups not only allow us to partner, but they also inform how we carry out our research. They’re the ones that a lot of time allow us to say, “Maybe we didn’t think of this right. Maybe this is the true question.” And a lot of times, I think what we have realized as a research group these days is that engaging them earlier in the conversation to actually help us as we develop a lot of our research questions and strategy, it’s critical for us to really move the field forward.

Chris Riback: Well, that is spoken like a true researcher who knows that great questions can come from anywhere.

Dr. Sonya Reid: Absolutely.

Chris Riback: I’m sure you’re keeping your ears open for them all the time. So let me ask you then another question, which is about you. Let’s talk about you. How did you get into this? And I mean, going back. I know that you grew up in Jamaica, but maybe you can talk about that. And was it always science and math for you, or did you have other interests that were going to take you in a different direction until the science community grabbed you and didn’t let go?

Dr. Sonya Reid: Wow, that’s an interesting one. It has always been science. I think that I knew. I actually always knew I wanted to be a doctor from very early. I don’t think I had honed in on what type of doctor. But yes, so science was always there, and going into medicine was always there. What I will tell you, I never thought I would fall into this passion, I always call it, because I never really thought about it initially, that there was a career maybe looking at disparities and breast cancer and all that. That’s really, I guess, something that more evolved over time. But I really think it started with my upbringing in Jamaica, if I’m being honest. Because growing up in an island where a lot of times opportunities for quality care is not afforded to our patients because of lack of resources, to put it very plainly, a lot of times patients just cannot afford different treatment, maybe it’s not even available in the country, then they just can’t afford it.

So I was faced with that growing up, and understood it very clearly. I went to medical school in Jamaica, so I saw that firsthand, spoke to patients in hospice settings, where sometimes patients in hospice, in my mind, I’m like, “Did they need to not get treatment?” In my mind, when you read the textbook, you would think, “Oh, but there is a treatment for this.” But they couldn’t get in to get treatment, or they got diagnosed at late stages because they didn’t get access.

So just different issues that really weighed on me, I believe as early as medical school, where I saw that just lack of resources essentially caused patients to die. And then I came to the United States for my residency training, and I saw a lot of the same issues.

Chris Riback: Interesting.

Dr. Sonya Reid: And I think that’s when a bell went off in my head, to be honest, because I thought to myself, “In this country where it’s a developing country you see some of these disparities.” But when I came to the US and you think, “Oh my gosh, there’s so many resources here,” but then I saw patients that had no insurance or under insurance, or Black patients in the county hospital here in Tennessee, that it’s almost as if I was right back in Jamaica. And I think it was appalling. I think at that point I was like, “How could this be, in this day and age, patients are not able to access a healthcare system because of just who you are?” So I guess that is full circle, really finding something that fueled me. And I really thought if I could be one person to try to be a part of the change, and that’s how I decided to go into breast cancer and breast cancer disparities.

Chris Riback: You’re taking your ideas, which are at the center of your work, but you have a team. You have partnerships in various countries, in various communities. You’re reaching out to various groups. So you are a person in the ecosystem, let’s say. But what I’ve learned among the things that I’ve learned from these conversations is I know you all feel the same way, that you’re one person, but you have such a powerful network. And that just grows everything exponentially.

Dr. Sonya Reid: Absolutely.

Chris Riback: Speaking of networks, how would you characterize, what role has BCRF played in your research and this Conquer Cancer grant supported by The Estée Lauder Companies’ Charitable Foundation Awards?

Dr. Sonya Reid: The Breast Cancer Research Foundation has been amazing. So this project would not have been funded without the Breast Cancer Research Foundation. So that’s for starters, that it has funded this idea that really started out as a junior faculty, just someone supporting your idea and funding that idea to allow me to have protected time to do this research is huge. I am very honored to be able to partner with such an organization. In addition, being able to collaborate with other BCRF awardees had been great because you can hear everybody else’s idea that practices across the different states and really pull from that energy and those collaborations. And I think that has been truly impactful as well.

Chris Riback: Yes, it’s a very, very powerful, fascinating, and energized network for sure. To close, and it’s funny because nearly all the comments I read about you and from you in preparing for this conversation mentioned this, and then you just used the word a moment ago, and that’s passion. It totally came across how passionate you are about your research. It came across in what I was reading. And it now has come across, of course, in this conversation. Why does passion matter? I mean, Dr. Reid, this is science. Many of us are led to believe that science is meant to be a dispassionate study of reality. Why does passion matter?

Dr. Sonya Reid: I think science is fun. I truly think that. I think it’s something that fuels discovery. It fuels the reason why I keep doing what I keep doing, keep fueling when I’m in that clinic with that patient and we’re running out of options. It actually fuels me to do more research to try to figure out how could we better treat these patients? That way I’m not here 10 years from now trying to tell someone that I don’t have any better option for you. So I think that passion truly keeps science alive. It keeps hope alive, because when you’re dealing with a disease like breast cancer that we have seen it, right? Mortality rates have continued to decline, albeit because of better screening, better treatment.

But I think when we’re not able to give those treatment advances or those better strategies to all of our patients, I think that’s something that without passion and with us just keep allowing it to just pass us by and we hear it, it’s almost like it reels off your tongue nowadays. I told someone recently, if I hear that 40 percent higher mortality rate one more time, I may scream, because you hear it over and over again. And I think we have been hearing it for a while now. And it feels like it’s not going anywhere. Unless we have enough people that are passionate enough about that to make a difference, then we’ll be here in years to come as well.

Chris Riback: Well, I hope that we are here in years to come, but talking about new topics and new advancements, many of which will have been constructed and advanced by you and your team. Dr. Reid, thank you. Thank you for your work. Thank you for your time. Thank you for your passion.

Dr. Sonya Reid: Thank you for having me.

Like so many medical challenges, breast cancer research reveals a long list of questions. What elements of our environment are carcinogenic? What role do factors like age, diet, and genetics play? And because cancer is biological in nature, many of us tend to think about the individual and their body as an obvious point of focus. What about, though, the larger, societal picture?

That’s what Dr. Scarlett Gomez and the field of social epidemiology are working to uncover. Dr. Gomez and her team have taken data showing that breast cancer risk in Asian Americans in the San Francisco Bay Area is rapidly rising to uncover structural and social determinants that influence that risk. And while Dr. Gomez’s work focuses on Asian American and Pacific Islander populations, that group includes people from 30 to 40 countries—each with different variables and risk factors to consider.

Dr. Gomez is professor and vice chair for faculty development in the Department of Epidemiology and Biostatistics and co-leader of the Cancer Control Program of the Helen Diller Family Comprehensive Cancer Center at the University of California, San Francisco. A BCRF investigator since 2022, Dr. Gomez’s grant is supported by The Estée Lauder Companies’ Travel Retail Award.

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Read the transcript below: 

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

Dr. Scarlett Gomez: Hi Chris. Thanks for the opportunity.

Chris Riback: So I think to understand this conversation and your, we should start at the core, or at least what I believe is the core of what you do for a living. What is epidemiology?

Dr. Scarlett Gomez: The million-dollar question. I would say if you had asked me that maybe 20 years ago or even 10 years ago, most people probably wouldn’t know. But I think with the very obvious global health issue we’ve been dealing with over the past three or so years, I think the field of epidemiology has become much more apparent to the general public. So broadly speaking, epidemiology refers to the study of disease, causes of disease, and its distribution within the population. I am classically trained as an epidemiologist, specifically cancer and other chronic diseases. And I’d love to talk to you in more detail about why cancer surveillance is actually such a unique activity. It’s the only chronic disease for which we collect population level information from everybody who’s been diagnosed with cancer. So we conduct studies to [look at] how cancer occurs within population groups with a strong focus on disparities within particular groups. And we also conduct studies to try to identify risk factors for higher rates in certain groups as well as factors that contribute to worse prognosis.

Chris Riback: So I was going to ask you about that. If your focus always was cancer, and I guess it sounds like it was, and so that makes me wonder why, what attracted you to that area of the discipline?

Dr. Scarlett Gomez: Lots of reasons really. I think like many of us who have been focused on this, on cancer and trying to address this problem of cancer in our society, we come from a place with having had personal experience with cancer. So I think, again, like many, it is a fairly common problem. So I have seen family members, friends who have been diagnosed with the disease, who have struggled with the disease. So from that, a personal interest in trying to understand the structural and social drivers of why cancer may occur more in some populations than others. I have always been drawn to the field of what’s called social epidemiology. Despite that I didn’t know that there was such a field of social epidemiology when I first learned about the idea that societal factors can impact upon disease, and understanding what those associations and patterns may be can help us to design potentially more effective interventions that alleviate disparities in cancer in different populations.

I started out my research career working in a very different field within a pharmaceutical company doing bioanalysis and metabolism research. How drugs are metabolized as [they] move through the body, and it just didn’t feel particularly rewarding because I felt that there was something bigger at the population level that I could be doing. And this was actually before I even knew about the term epidemiology, and that it was actually a field of study. So I took a break and I studied, I embarked on a master’s program in public health where I focused on epidemiology.

And there was at the opportunity to train under Dr. David Schottenfeld, who literally wrote the book on cancer epidemiology. He and Dr. Joe Fraumeni authored. I think they’re now on the sixth edition of the book called Cancer Epidemiology. And that really started cementing my interests and bringing together my personal interest and personal desires to want to understand in particular what we can really do in a meaningful way to address the disparate burden of disease in different populations.

Following that exposure, I had the opportunity to do an internship at a nonprofit organization called at the time Northern California Cancer Center, which then changed its name to Cancer Prevention Institute of California. And I ended up working there for the next 25 years until I moved to my current role here at UCSF about six years ago.

Chris Riback: What an incredible and fortunate thing to have an interest and skills combined and then to be able to make a transition like that. So many of us end up in one role and sometimes feel, and I’m not just talking medicine here, obviously any role, any profession, and one can start to feel like, “Well, I chose the wrong path finding a way out becomes difficult.” I strongly believe one makes one’s own luck, so I don’t characterize it as lucky. I’m sure it was your own initiative, but what a fortunate and excellent thing to get to make a shift like that.

Dr. Scarlett Gomez: It absolutely was luck and in fact, it was really one individual at this pharmaceutical company that I had worked at. He was my informal mentor. We would be pipetting side by side along our lab bench and he would just tell me stories about the six years that he worked in the Peace Corps in rural mountainous Nepal and all the public health and hygiene issues that the populations there had to deal with. And that was when I thought, “Maybe there is a field of study that deals with these issues and its impact on health.” And I think the other way that I was able to marry those interests was in my undergraduate training, even though I was on this straight and narrow path.

Chris Riback: Molecular and cell biology, if I recall, is that right?

Dr. Scarlett Gomez: Molecular and cell biology, because I thought that’s what you needed to major in if you wanted to eventually go to medical school. But I also took a lot of classes in anthropology and social sciences and behavioral health, and I think that actually has been a really good critical foundation for the work that I do today.

Chris Riback: Well, shout out to your former lab partner or pipetting partner.

Dr. Scarlett Gomez: Larry Bowen was his name, I still remember.

Chris Riback: Shout out to Larry. Dr. Gomez, let’s talk about your current research. How and when did you learn that breast cancer risk in Asian Americans in the San Francisco Bay area is rapidly increasing?

Dr. Scarlett Gomez: Yes. So it’s essentially something that our group has been keeping an eye on for quite some time. So, this internship that I had the opportunity to do when I was working on my master’s degree in public health was at this organization that actually ran the cancer registry for the San Francisco Bay Area. Cancer, as many people may know, is a state-mandated activity. Every state, in addition to every Canadian province, has some law that mandates its collection. So if you’re a healthcare clinician provider who’s recently diagnosed or treated somebody with cancer, you are required by your state’s law to report that to your cancer registry. So I was involved and gained exposure to the cancer registry in the Greater Bay area. Much of the funding for our registry actually comes from the NCI (National Cancer Institute) as well as the State Department of Public Health.

So you can imagine what a rich resource of data that is because it is effectively every single person diagnosed with cancer in a defined attachment area. And that is what allows us to track what’s going on in cancer occurrence by different population groups. It’s also the data we use for what we call cancer cluster investigations. So the CDC also invests money into these states and regional cancer registries. So every year we undertake a thorough investigation, a deep dive into the data in our registry to look and see for whom is what’s going on with cancer in our different regions, in our different geographies and our different population groups defined by sex, race, ethnicity, age, et cetera.

And it’s through these kinds of routine surveillance activities that we started to see an interesting shift in breast cancer patterns by race and ethnicity groups in our area such that despite that breast cancer rates have been generally going down over the past about 10 or so years across almost all of our racial ethnic groups. An exception to this would be among African American women where we have been seeing a slight increase. Among Asian American women that’s actually has been rapidly increasing. So, we’re seeing something closer to at least a 10 percent increase in the incidence of breast cancer per year.

Chris Riback: Per year?

Dr. Scarlett Gomez: Yes, per year, about 10 percent increase in breast cancer.

Chris Riback: When did the curve start to shift?

Dr. Scarlett Gomez: I would say it probably started in the 2000s.

Chris Riback: 10 percent a year for a good 15-ish, 20-ish years?

Dr. Scarlett Gomez: Yes.

Chris Riback: That’s a big deal.

Dr. Scarlett Gomez: It is a big deal. I feel that this trend does not tend to get as much attention in large part because we don’t commonly report on cancer rates among Asian American populations are often combined collectively as a group, Asian American, Native Hawaiian, Pacific Islander populations, or AAPIs. When in fact these, if you consider the AAPI or API population, that represents people from 30 to 40 different countries, over 100 different languages. [It’s] highly, highly diverse. And when we start to disaggregate the data, we actually see very divergent patterns. So we’ve done a lot of work just looking within our cancer registry data to see which Asian American, Native Hawaiian, Pacific Islander groups are seeing increasing rates of breast cancer. We actually noted that it’s rapidly increasing nearly all with the interesting exception of Japanese Americans who have been here much longer than other Asian American groups.

And the other interesting finding that has been starting to emerge is that when we look at international data, so breast cancer rates in Asian countries, we’re seeing similar increases. So, it’s really not unique to Asian Americans here in the US—it’s really happening worldwide. The other interesting pattern that we’ve noted is that whereas we are used to the traditional what’s called the migrant paradigm of Asians who come from Asia, their risk is low because risk tends to be lower in Asian countries. And as they start to adopt more westernized health behaviors that are now correlated with increased breast cancer risk, their risk start starts to go up. So we see increasing risk with subsequent generations of Asian Americans.

One recent study that we did showed that, that was reverse in the Bay Area. So in fact in this particular study, we saw higher risk of breast cancer among foreign-born Asian Americans relative to their US-born counterparts. And this was not explained by the known risk factors for breast cancer. When we thought about that pattern, firstly we thought there must be something wrong with our study. We did it wrong. But when you consider the international data, the fact that breast cancer rates have been increasing really rapidly in certain Asian countries to the point that it’s projected that breast cancer in Asia will likely surpass become among the highest in the world.

So the studies in Asia have actually documented and shown that given the rapidly increasing rates of breast cancer that they’ve been seeing, these are studies that have been done with data from Taiwan, Hong Kong, Korea, Singapore, parts of China, that soon we will actually see the highest breast cancer rates among Asian women in Asia. So when we consider that vis-a-vis what we saw with this flip of breast cancer risk comparing foreign-born to U.S. foreign women in the San Francisco Bay Area, it made sense because when we consider who’s been immigrating to the Bay Area over the past 10, 20 years, they have tended to be professionals, particularly those in the tech sector, those in the health sector.

And also when you think about the high costs of living in the San Francisco Bay area, who can really afford to live here and settle here, and in fact some demographic data have documented that when you look at the most recent waves of immigrants, they have tended to have much higher levels of education than prior waves of immigrants. So that all plays into what we’re seeing in terms of rates of breast cancer and these highly dynamic populations like migrant populations in the U.S. So, we think that to the extent that we still have much to learn about what causes breast cancer, both genetically and from a risk factor standpoint, focusing studies on these highly dynamic heterogeneous populations could potentially teach us something about what some of these risk factors might be.

Chris Riback: So you might have just answered what I was going to ask, which is what are you proposing to study? What’s your hypothesis and how will you proceed?

Dr. Scarlett Gomez: Yes. We’re super excited because I think this support from the Breast Cancer Research Foundation, it really gives us the opportunity to do something to focus on this area that we, I think, may not have been able to focus on with more traditional streams of funding. So we are proposing and we are conducting what’s called a case-control study of breast cancer. This means that we are collecting information from women recently diagnosed with breast cancer, specifically Asian American women from a defined catchment area. Here, we’re starting with the Bay Area in addition to we’re expanding to LA, Southern California, and we will also recruit and collect information from matched controls—that is, Asian American women from the same regions, but without prior diagnosis of breast cancer. And by collecting information regarding their past exposures in addition to samples that will allow us to look at some genetic and molecular factors, then we can compare and see which factors are we seeing higher levels of among the cases compared to the controls.

Importantly, the way that we’re doing this study is that we’re recruiting through these cancer registries. So our sampling base is then everybody who’s been diagnosed with breast cancer within a particular defined geographic area. So that from an epidemiologic study design standpoint minimizes bias where asked if you were to recruit, for example, from one healthcare institution, patients from that given healthcare institution may be different and not represent the overall population. We hope that this will be, once women are recruited into this study, they will remain engaged and hopefully provide an opportunity for us to go back to them over time to collect additional information as the study involves and as perhaps emerging hypotheses might come out. But initially, we’re really interested in exploring hypotheses related to stress. Even just this morning, I was talking to a colleague again who had a personal struggle with breast cancer and she herself is a cancer epidemiologist, and she said, “I’m convinced that stress cause my breast cancer.”

And that’s probably the most common thing we hear from patients when we have an opportunity to talk with patients, but we don’t have good evidence. I mean, it’s been scattered and mixed in terms of what we know about stress and its impact on breast cancer risk. And to the extent that some of our Asian American communities have faced historically tremendous trauma relating to their migration experience, relating to the reasons for immigration, relating to settling into a completely new life in a different country for which they don’t speak the language, and acclimating, in addition to recent experiences with discrimination and structural racism as a result of the COVID pandemic. I think that has been understudied area, but potentially could give us some insights into the role of stress and stressors, coping resiliency as it potentially relates to breast cancer risk.

Chris Riback: And this obviously is, well, and I would assume this is out of scope, but a question that comes to my mind would be comparison to other immigrant groups, but maybe you answered that in the first place by saying, well, it’s the Asian American data that has grown so rapidly, 10 percent a year for the last 15, 20 years that’s why that’s a group of interest. We’re not seeing that with other groups. Am I both asking and answering my own question?

Dr. Scarlett Gomez: Well, I think the increase is a motivation for us to be focusing on this particular population because it’s something that’s happening, has been happening, is continuing to happen, and we need to understand why. At the same time, from a data standpoint, when you see such dynamic changes like that, it provides statistical variability for you to be able to be more likely to find patterns and associations. So it’s really a unique window of opportunity for us to potentially discover something new about breast cancer and its causes. But I think that some of the exposures that we’re focusing on are really quite unique to the Asian American diaspora.

And in fact, the challenge we’re having is how do we come up with a way to ask a certain question about a life experience that really is applicable across the diverse Asian American population. But I think the approach we need to be taking is recognizing the unique life experiences in our diverse communities and to design studies that tap into and capture those unique experiences.

Chris Riback: So what’s next? Is it literally having those conversations, starting that research and gathering the additional information?

Dr. Scarlett Gomez: Absolutely. Yes. We are starting recruitment. We have a survey that’s been finalized. We’re in the process of engaging, we have a vast network of community organizations and collaborators, and we’re really interested in hearing from women in the communities about what they think about breast cancer. We also, through some of our experiences with, we have a whole other portfolio on lung cancer among Asian American women who’ve never smoked and have learned that through the community engagement process, just getting the word out there has really allowed us to increase awareness about the issue among this community. So we’re hoping that this will provide an opportunity to do that as well.

Breast cancer remains really a stigma in our communities, and it’s not something that the community members talk about and because of that, so they’re not often aware of their risk of breast cancer. And that plays into some of our groups actually being diagnosed at later stages of disease because they are not up to date with regular screenings, do not follow up on concerning symptoms. So we hope to at least get the word out and to increase awareness about breast cancer among Asian American communities.

Chris Riback: Yes. I have heard about that problem with other groups and in other countries, not just in the U.S. but in different areas of the U.S. and in other countries. And what a wonderful initial benefit that you’re generating just by taking on the work, if you are almost as an externality, creating some initial awareness and getting people because, yes, the delayed diagnosis that can occur for a range of reasons, lack of access, cultural reasons, there are all sorts of reasons. Just to close out, I know you mentioned very briefly, but your BCRF grant is currently supported by The Estée Lauder Companies’ Travel Retail Award. What role would you characterize that BCRF has played in your research?

Dr. Scarlett Gomez: Yes. I think just to expand a bit about the comment I made earlier about this funding just being so unusual because I think this study that we’ve designed is not really something that could traditionally be funded through a grant, that one might write to, for example, the National Institutes of Health, for it to be funded. So I think just in itself, the fact that BCRF is willing to fund this, we think important work that I’ve been wanting to do for a long time and that many in our communities have been wanting to do for a long time is the major contribution.

I also had the opportunity back in October this past year at the BCRF Symposium and Luncheon to sit down and talk with some of the members from The Estée Lauder Companies’ [Travel Retail channel], which is supporting funding this research in addition to other [BCRF research projects], and hearing from them that they raised funds among their employees within [Travel Retail] and [elected to support] research on Asian American populations. So that actually was very meaningful and meant a lot to me. So, I feel especially grateful, but also responsible for the stewardship of these funds and making sure that we generate findings and data that are meaningful and impactful.

Chris Riback: I was going to say, I’m sure grateful, but also motivated. There’s another level of motivation. Dr. Gomez, thank you. Thank you for your time and thank you for the work that you do.

Dr. Scarlett Gomez: Thank you, Chris.

While academic and medical research has led to incredible breakthroughs in breast cancer care—including new treatments and screening methods—these advances have not reached every patient in every corner of the globe. With breast cancer now the most commonly diagnosed cancer in the world, it’s critical that lifesaving advances are deployed more equitably and universally—especially to women and men in lower-income and -resource countries.

How can the gap between high- and low-resource countries be bridged? How can you translate valuable medical knowledge to countries with different healthcare infrastructures?  

Each year, BCRF underwrites several grants to breast cancer researchers in partnership with Conquer Cancer, the ASCO Foundation. Dr. Temidayo Fadelu recently received the Career Development Award for Diversity, Inclusion, and Breast Cancer Disparities. Dr. Fadelu was a prior recipient of a previous Conquer Cancer–BCRF Young Investigator Award.

Dr. Fadelu is a medical oncologist and instructor of medicine at the Dana-Farber Cancer Institute whose work focuses on global equity in breast cancer. His BCRF-supported project aims to improve adherence to endocrine therapies among patients in Rwanda and Haiti. 

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Chris Riback: Dr. Fadelu, thank you for joining. I appreciate your time.

Dr. Temidayo Fadelu: Thank you, thanks for having me.

Chris Riback: So this is not scientific, but I often feel that if you want to know what a person really cares about, you’ll look at their Twitter bio. And on your Twitter bio, you list all the important elements, oncologist, hospital, and university affiliations, the fact that you’re an impromptu cook, which I think will make for an excellent follow-up podcast conversation with you, but also the words in your bio, cancer equity. What does cancer equity mean to you?

Dr. Temidayo Fadelu: Thanks for that question. I did not expect people to refer to my Twitter bio. And so, I think to me, cancer equity is patients from anywhere in the world having access to the appropriate type of cancer care that that patient needs. So there is a lot in that, in the sense that the type of care a patient needs to sort of customize to their own specific needs. And when I say access, access is a relatively complicated word, because access can mean geographical access, economic access, and a variety of other elements of access as well. So to me, it’s folks really having the care that they need in a way that is accessible to them.

Chris Riback: Yes, and obviously that’s where you have dedicated so much of your energy and efforts over the years, and I look forward to asking you about some of the specific current efforts that you have to kind of close that gap. But the research of yours that focuses on the disconnect between evidence-based knowledge and integration into real world clinical practice, describe that disconnect for me, because I think that for us to understand that disconnect gets to the heart of so much of what you do.

Dr. Temidayo Fadelu: So, in the academic world, and in the research world, there are lots of studies that get done and studies are usually done in an idealized setting, so be it testing of a new medication or investigating the reasons for why something is a particular way, and a lot of knowledge gets generated. And the question is, what happens after that knowledge gets generated in the context of a research study?

So one element of the disconnect when it comes to lower resource settings, for example, settings like Rwanda, or in Haiti where I work, is that many of the studies that generate the knowledge are not done in those settings, the studies might be done in higher resource settings, and there’s always the question of how translatable the findings are from the higher resource settings to the lower resource settings.

Another element of this, as well as even studies that are done in lower resource settings are usually done in a way that requires a lot of support to carry on the study. And after the study ends, many times there is a gap between translating what is found in that setting to actually impacting patients locally as well.

So an emerging field called implementation science, and the goal of implementation science is to try to bridge that gap, so not just finding out whether or not something is efficacious or generating knowledge, but figuring out the most appropriate way of implementing the findings from the knowledge that is generated to impacting people in a local way. So, as you can imagine, implementation science really needs to take into account the context in which you’re working because the context is really important. So even if you find something somewhere, really recognizing the context in which you want to implement it is quite important.

Chris Riback: One size does not fit all.

Dr. Temidayo Fadelu: Correct, one size definitely does not fit all. And a lot of my work currently has been in utilizing some implementation science principles to improve the type of care patients are getting, specifically breast cancer patients in Rwanda and Haiti.

Chris Riback: Is the challenge in the first instance to simply understand the facts on the ground. It’s hard to even get a lay of the land because there’s not even enough primary or adequate primary research going on in those locations, am I understanding that part of the problem correctly?

Dr. Temidayo Fadelu: Yes, that is most certainly a huge part of the problem in many low income countries. Traditionally many of those countries had focused the healthcare systems on other types of diseases, specifically communicable diseases and infectious diseases. So there traditionally has not been a strong background of primary data and primary research in oncology in these settings. So some of the initial work that we’ve done in Rwanda has really been, let’s just get the lay of the land of what’s the current state and what’s the current status of things and understanding that helps you also understand gaps, and then you can employ strategies that have been used in other places, but in a way that is contextually appropriate to fill those gaps.

Chris Riback: What struck me as well was some of your data around breast cancer does not discriminate, I assume, between high income, middle income and low income countries in the initial instance, correct? I can assume in kind of an even distribution regardless of the economic status of the country itself?

Dr. Temidayo Fadelu: It is a little bit more complicated than that, but you are absolutely right that breast cancer does not discriminate. And in the past there was the thought that low-income countries would not suffer from oncologic problems, but that’s certainly not the case. So breast cancer occurs everywhere around the world, however, there are some social and other factors that increase the risk of having breast cancer in some places. But you’re right that breast cancer occurs around the world.

Chris Riback: If I’m understanding correctly, the most heart-wrenching problem is that early recognition really matters. Once it’s recognized early, continual regularized treatment really matters. And that’s where the data show just the cliff drop that while maybe the initial instances are basically averaging out about equal-ish across the globe a real disparity in how many of those cases result in a patient’s death, I guess, in a sense dependent on where they live. Is that accurate?

Dr. Temidayo Fadelu: Yes. And there’s certainly huge disparities in this. So if you lived in the US or in Northern Europe, first, your breast cancer will be diagnosed at an earlier stage, and when you actually look stage for stage, you certainly will have a much higher survival rate. And so the patient having breast cancer in the US and Northern Europe has an over 80 to 90 percent chance of survival over five years, depending on what the stage is. However, if you’re a breast cancer patient in a lower resource setting in Sub-Saharan Africa, you might only have a 50 to 60 percent chance of survival. And there’s a lot that comes in there, and so part of it is the stage of diagnosis, part of it is really the inaccessibility of curative treatment. So even patients with curative disease are still doing poorly in Sub-Saharan Africa.

Chris Riback: So this segues, I believe to some of your current research, and that’s your effort in improving adherence to adjuvant endocrine therapy among patients with breast cancer in Rwanda, the randomized intervention of symptom, self-monitoring, and motivational mobile text message reminders. So describe that effort for me, what is your strategy? When did you start? Where are you in the process? How will it work?

Dr. Temidayo Fadelu: Okay, thank you for that question. So this is a study that was recently funded by the Breast Cancer Research Foundation, as well as the ASCO Conquer Cancer Foundation, so we’re just in the early stages. So the overarching concept here, as I mentioned, is trying to improve the care that patients get. In this particular case these are patients who have estrogen receptor-positive breast cancer, and in this particular population, adjuvant endocrine therapy, that’s endocrine therapy that patients get after they’ve had surgery, and folks who need chemotherapy after they’ve done some chemotherapy. And this is oral medications that patients will take for at least five years, and adjuvant endocrine therapy is almost as important, or just as important as chemotherapy in this population.

These are medications that are old and have been available for a long time, and they’re also medications that you take by mouth. So in a setting like Rwanda and in other low resource settings, these are therapies that are already available. So the main question is how do you improve patients adherence to these medications? So there really has not been much in the literature, really assessing how well patients are doing with adherence to these medications.

Chris Riback: So if I can just clarify and make sure I’m understanding your point there: We can get the medication there. It’s not a question of whether the medication exists or if it can get kind of physically to the country, it’s at that point, that there’s the gap in the understanding and then I think your conclusion is challenges in terms of maintaining the treatment, is that right?

Dr. Temidayo Fadelu: Correct. So, the concept of adherence sort of goes to the multiple elements of adherence. One is starting the treatment, the other part is actually taking the treatment the way it’s prescribed, so taking it on a daily basis in this case, and then the other challenge is taking it for the duration for which it’s prescribed, so taking it for, in this case, at least five years. So there are challenges at each of these steps. So right now we actually don’t know what the magnitude of the problem is. From some of our studies we’ve been able to understand the problem a little bit, but we actually did not know it completely. So, we know that only about 85 percent of eligible patients initiate the treatment, and we also know that about 40 percent of patients for whatever reason end up being lost to follow-up within the first two years.

So part of this study, the first part of the study is really trying to understand the different elements of adherence within this population. So the first part is a mixed-methods study which involves interviewing patients, but also there’ll be a survey of patients sort of understanding what are the things that contributes to whether or not patients are adherent.

Chris Riback: And what’s your hypothesis going in and based on the work that you’ve done over so many years, is it not enough facilities within the facilities? Is there more of a focus on the initial diagnosis and the surgical treatment, but maybe not as much focused on the continuing care? Do people live too far away? Is it something cultural? Is it A, B, C, D, are you going to choose E, all of the above? What’s the answer here, doctor?

Dr. Temidayo Fadelu: It’s probably a little bit of everything, and so that’s the main reason we’re doing this first part of the study, is many times people jump into the intervention without necessarily really understanding the problem. And in this case, it’s really important to try to assess what the problem is. Even if we know that patients are not “adherent”, what are the reasons why they’re not at adherent?

Chris Riback: What’s the root cause?

Dr. Temidayo Fadelu: Exactly, that would really impact what you do. So certainly based on some of the previous studies that we’ve done, there are some things that we certainly know are problems. So patients have to travel from far away to get the medication. There are certainly side effects from the medication, so how much are those side effects impacting in what patients do? How much does education of patients on those side effects actually impact what they do with regards to allowing them to know, and empowering them to know the importance of the medication and the purposes of the medication, and how does that impact what they do? And empowering patients to also manage those symptoms so that, or simply asking them about those symptoms so that they let the clinician know what’s going on.

Dr. Temidayo Fadelu: And in the case of Rwanda, these medications are available to patients at no cost, so the cost of the medication itself should not be a problem. Nonetheless, there are a variety of other costs that come into play for patients, specifically travel costs. And that’s one of the things we showed in a previous study that travel costs can be quite significant.

Chris Riback: So much of your research in your studies, it has seemed to me focused not just on the medical science, but also the costs around it. To what extent do you feel that you’re a part-time oncologist, but a full-time economist?

Dr. Temidayo Fadelu: I most certainly would not call myself an economist.

Chris Riback: But the cost component, it’s not just a science problem, it’s not just a medical science problem that you’re dealing with. I know you’ve also recently published research looking at breast cancer outcomes in Haiti, and you did this with, among others, Dr. Lawrence Shulman, an incredibly inspiring doctor who also was a previous guest on this podcast. Did your findings in that research, particularly recognizing that most Haitian patients are diagnosed at later stages, did that research inspire the Rwanda efforts? Or do I have the timeline wrong and you already were in Rwanda?

Dr. Temidayo Fadelu: So, I started working in Rwanda first, actually. So after I completed my internal medicine residency in 2013, I moved to Rwanda and I was working at the cancer program at Butaro Cancer Center of Excellence, and I lived and worked there for two years. And then moved back to the US, and I’ve been living in the US since then. And I started working in Haiti in 2016, so I’ve kept long-time collaborations with both countries, so I’ve continued working in Rwanda, but also worked in Haiti. And so the work in both countries have inspired one another. Even though the countries are quite different, there are some themes that cut across the different places.

Dr. Temidayo Fadelu: So, patients have limited resources in both places. The health care system is different in the sense that Rwanda has a national insurance scheme, which does have an influence in what type of access patients might have, and that is not the case in Haiti. And both the geographic nature and the location of facilities also sort of has an impact of patient’s accessibility to those places as well.

Chris Riback: Going back then to your study in Rwanda, you know there’s a problem, but you’re trying to diagnose, you need to diagnose the root causes of the problem. But my understanding is that some of the tactics, and I imagine you’re not going to implement tactics until you understand the root causes, but some of the tactics that you are thinking about include the motivational mobile text message reminders and other capabilities for self-monitoring. Do I have that right? And are these tactics, have you used these elsewhere? What’s making you think that these are the types of tactics that might make sense?

Dr. Temidayo Fadelu: Yes. Yes, so the choice of those two as part of a potential slew of interventions was based on review of the literature, specifically review of the HIV and TB literature in Sub-Saharan Africa, because HIV medications and TB medications are also oral medication and there’s actually been a variety of studies that have been done in the Sub-Saharan African context. So even though it’s not necessarily [the same] as a cancer, there’s certainly some literature from that, as well as looking at the broader literature on adherence to adjuvant endocrine therapy. So based on those, and also based on some studies and evaluation we did specifically in Rwanda.

So, we did a survey asking patients about their use of technology, specifically, what type of technology they had access to, how were they using mobile phones, if they had access to mobile phones, as well as what the patient’s preferences are with either text messaging or calls or other types of functionalities with the phones. And we’re also currently finishing up a prior study which is a pilot study where we’re piloting text messaging in a few number of patients, and we will do some qualitative interviews with those patients at the end. So those are the things that influenced our decision for suggesting that these might be interventions that might potentially work.

I should also mention there have also been some studies that indicate that text messaging has not been as effective in Western population, specifically in the US. So our goal was not necessarily to replicate exactly what was done in the US, and given some indication that text messaging alone wasn’t going to be effective, we wanted a multifaceted intervention. So the content of the text messaging, in this case, motivational messages, and also empowerment of the patients, in this case, we wanted them to record their symptoms, but also they’ll get suggestions on how to manage your symptoms, and doing those remotely as a way of bridging the patients in between appointments so that they could take their medications.

Certainly, part of this project after the completion of the survey is really asking patients what intervention, not just, but also there’s a process called implementation mapping where you get experts, local experts, so local clinicians, patient advocates, patients, content experts in breast cancer –

Chris Riback: A whole ecosystem, it sounds like.

Dr. Temidayo Fadelu: Exactly, get everyone on the table saying, here’s a certain intervention we’re thinking about implementing, let’s sort of work together to figure out if those interventions actually make sense and selecting a package that makes sense, and then figuring out exactly how to implement them. So there are going to be multiple steps prior to getting to the randomization. So the project is a three-year project, and we’re really at the beginning, so the randomization comes later on.

Chris Riback: So, as you are kind of launching into this journey on this research, what is the role for you of BCRF, and what would you ask of the rest of us? What should the rest of us think about, or even, God forbid, do that you would ask?

Dr. Temidayo Fadelu: Well, the second question is the harder question, so let’s talk about the first one. So BCRF is supporting this work through the work that they do with the Conquer Cancer Foundation. And BCRF also supported a young investigator award that I got, which helped create some of the preliminary data, and that feeds into this work. And BCRF is also supporting some other work in cancer screening and early detection in Rwanda as well. So, I’ll say, BCRF has really been quite instrumental in helping to really understand some of these contextual factors and hopefully in the implementing and testing of a variety of interventions as we go forward.

And specifically, for me, I think, these grants or fundamental grants are really early career development grants for me, and they’ve helped with helping me generate this data that can then be used for much more substantial, larger grants in the future from BCRF and from other foundations as well. And also, national funding from the National Cancer Institute.

What can other folks do? I’ll say, everyone, can try to learn about what’s going on out there. So I think first each person thinking for themselves, what do they want to learn about, and in what way do they think they can contribute? So some of the work that I’m doing currently, as you sort of indicated, does not necessarily require a medical degree.

Chris Riback: Good, then I’m qualified.

Dr. Temidayo Fadelu: Yes, you are in fact qualified because potential interventions might be patient education materials. So creating the content of the patient education materials would require some knowledge, but formatting the patient education materials, putting it in a way that is in fact accessible to patients, it’s something that is beyond what I can do, so getting collaborators to do that. Many of the patient education materials are in paper, and we in fact know there is a low literacy level amongst our patients, so we try to have pictorial representations.

But one of the visions I have in the future is having questionnaires and patient materials in an audio version or a video version in a way that is in fact much more accessible to the patients, where they can have access to it remotely. We found out that the vast majority of our patients have phones, the vast majority have smartphones, so there are ways of doing things in a way that is more accessible to patients, which certainly requires a variety of expertise beyond what I have.

So, I do work with collaborators with patient advocacy groups, and specifically cancer survivors as well. And another project that we’re currently working on is understanding breast cancer stigma, and how to work with family members in understanding the state of what patients undergo with their family members.

Chris Riback: Specifically in Rwanda or in multiple locations?

Dr. Temidayo Fadelu: Specifically in Rwanda. And as a part of that project, we are going to be trying to develop interventions as well. And some of the potential interventions is utilizing breast cancer survivors as partners with patients, but doing it in a way that is proactive, such that patients and their families have access to a variety of resources that can potentially help them.

Chris Riback: So that would seem to be incredibly powerful, not only the one-on-one capability of yes, to whatever extent there is stigma, but to be able to talk to someone who has gone through it and survived. But also potentially, if you are distributing audio or video materials to mobile phones as a way for future encouragement, boy, those survivors would make remarkable spokespeople, wouldn’t they?

Dr. Temidayo Fadelu: Yes, absolutely. So those are potential ways in the future that I think people can help.

Chris Riback: There are so many challenges that many of us don’t even know in the first instance that they exist. To close out the conversation, let’s talk about maybe the one thing that, I’m just guessing, judging by your personality, you would hate to have to talk about. Let’s talk about you. How did you get into this? And I mean, going way back I know that you did not grow up here in the US, but for you, was it always science?

I did read that your medical school thesis evaluated brain drain and migration patterns of physicians from Sub-Saharan Africa to higher-income countries. I can only assume that that was your autobiography that you wrote, and I’m glad to know of course, that you all are going back and spending time back in Africa as well. But tell me, how was it for you growing up, and was it always science, was it always research?

Dr. Temidayo Fadelu: Yes, well, so I’m originally Nigerian, I grew up in Nigeria. And I moved to the US for college, so I was in Nigeria up until high school. And it is sort of a complicated question. So let’s put it this way, so I was always interested in science and math. So going back to elementary school, I was always sort of interested in math, I don’t know why I didn’t become a mathematician with my interest in science and math. Actually, I do remember why I did not become a mathematician, calculus in college was hard so that changed the course.

Chris Riback: Yes, that derailed many of us, for sure.

Dr. Temidayo Fadelu: Yes, but in Nigeria, in high school, you also decide on a general path. And so you have to sort of decide if you’re on a science path or an arts path or a business path, and so I’d sort of gotten into the science path based on my interest in elementary school. And at the end of high school, you take exams that are specific to the path you were on. So in a way, my career in science was sort of defined from high school. And I had also started university in Nigeria before I moved to the US, and in Nigeria, medical school is an undergraduate degree, and so I was in medical school at the University of Lagos.

So, when I came to the US a year after high school graduation, I sort of was anchored on the idea of medicine because I was already in medical school, so I did struggle a little bit decided on what majors to do in college. Another thing I enjoyed at the time was environmental studies, because I had asthma growing up as a kid, and I was sort of interested in the idea of pollution and how pollution impacts breathing and waste management, and things of that nature.

So, a long story, in college I was a biology and environmental studies major, as I was pre-med, and decided on the medical school route. I think part of it was based on my experiences growing up, so my experiences with asthma and illness. And part of it was also based on my family’s experience because my dad passed away at the end of high school and he had hepatitis as well as hepatocellular carcinoma. And at the time I did not recognize that he had cancer, and it’s something I later discovered after having a little bit more knowledge, and so I think that certainly had an impact on my wanting to do something within medicine.

I should also mention that my mom also had breast cancer when I was living in Rwanda, thankfully she is doing okay. And so the experience of cancer is a personal one to me and my family. And the narrative of cancer not being a problem in many low-resource settings, to me seemed clearly wrong. So that motivated what I did in medical school as well as going on to internal medicine and oncology.

Chris Riback: Well, certainly that would be clearly very, very powerful motivation. And I guess our hope then is, once you solve this cancer thing, then you can return to environmental science and solve the climate change thing. You could deal with both of them for us, couldn’t you?

Dr. Temidayo Fadelu: Unfortunately, the environmental ship has sailed.

Chris Riback: Oh, okay, okay. Then we’ll only hold you to solving cancer.

Dr. Temidayo Fadelu: Yes, yes. Well, we jointly as a world we can make a dent in cancer.

Chris Riback: Certainly. Well through efforts like yours and the other folks who I’m fortunate enough to get to speak with, every effort is obviously being made. Dr. Fadelu thank you. Thank you for your time, thank you for the work that you do every day.

Dr. Temidayo Fadelu: Thank you. Thanks for having me, and thanks for this opportunity to share with all of your listeners.

While breast cancer is not typically caused by inherited factors, as many as 10-15 percent of people diagnosed with breast cancer carry a known genetic mutation. The most well-known mutations are in the BRCA1 and BRCA2 genes. But these only account for 5-10 percent of inherited breast cancers, so what about the many other gene mutations that increase a person’s risk of breast cancer?

One major BCRF-supported cross-institution study, CARRIERS, found—among other results—that some mutations that had previously been linked to breast cancer were found not to increase the risk of disease.

What does this mean not only for genetic testing—but also how we should consider results? More significantly, what effect might this have on the personalization of risk?

BCRF investigator and cancer geneticist Dr. Katherine Nathanson was one of the study’s principal researchers. She is deputy director of the Abramson Cancer Center and the Pearl Basser Professor for BRCA-Related Research in the Perelman School of Medicine at the University of Pennsylvania. She not only runs a prominent research laboratory but also maintains a clinical practice. 

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

Dr. Katherine Nathanson: Glad to be here.

Chris Riback: Let’s start by understanding some of the background of hereditary breast cancer and the mutations. Most of us have heard of mutations in the BRCA1 and BRCA2 genes. But those aren’t the only mutations, obviously, associated with breast cancer, are they?

Dr. Katherine Nathanson: No. So we think about breast cancer susceptibility as a spectrum of susceptibility. So, you have your high penetrance genes, in which mutations are associated with a relatively high risk. So usually BRCA1 and 2, for example, that’s associated with a high lifetime risk. Then you have your genes in which mutations are associated with what we call a moderate lifetime risk, usually in the range of twofold. There is a gene that’s sort of in between, which is called PALB2. But there is a gene that’s associated with a moderate lifetime risk, which is CHEK2, ATM, and things like that. And there are a set of what we call normal variation. Sometimes those variants are associated with minimally increased risk, but when we put all those variants together, we get what’s called a polygenic risk score, or lots of variants together to try to think about risk.

So the way that I talk about it, which hopefully is helpful, is everyone gets dealt a hand of cards. And sometimes when you get dealt a hand of cards, you get the ace of spades. You know what the ace of spades is. It’s a really high card. It means something really important. That’s your BRCA1 or 2. You have a moderate penetrance gene. You get dealt a hand of cards. Queen of clubs, it’s helpful card if you’re playing Bridge. But it’s not the best card. It’s not the greatest card, but it’s there. And then you get everything else. Your six of diamonds, your eight of spades. And those are your normal variation. But when you put all those together, sometimes they can make a very powerful hand of cards.

And so if you think about the different genes in which there are mutations, you can think that everybody gets dealt a mixture. Sometimes you get different hands than others. Everybody gets dealt a mixture of those sort of hands. And some of them are high, some of them are moderate, and some of them are low combinations. This is the way I sort of think about an analogy to help people out.

Chris Riback: It’s really helpful, and it makes me wonder. Which hand is the most common, and which hand is the most worrisome?

Dr. Katherine Nathanson: So the hand that’s most common is probably the hand, I don’t know if anyone plays Bridge. Right. The hand that you get the bunch of dreck [trash]. And it’s like, you’re just playing it defensive. That, in fact, in this sense is probably the better hand. Right? And the more unusual hand is when you get the high cards. And it’s much more unusual to carry a BRCA1 and 2 mutation than it is to get the sort of regular hand of assorted not-so-great cards.

Chris Riback: And so, how would you characterize the extent to which those mutations, the extent to which they increase breast cancer risk or are associated with breast cancer risk, compared to the BRCA1 and BRCA2?

Dr. Katherine Nathanson: So like the queen of clubs in the analogy that we were just using.

Chris Riback: Yes.

Dr. Katherine Nathanson: So those increase your risk modestly. So, it depends on the gene, but instead of for example, you have to remember that any woman in the US has a 12 percent lifetime risk of breast cancer. So just to point that out, right? So, these increase your risk potentially to 20 to 25 percent. That’s higher, and we can show in large studies significantly higher. But it’s not nearly as high as a BRCA1 or 2 mutation. And in that context, actually, the other cards are much more important.

Chris Riback: Why is that?

Dr. Katherine Nathanson: It’s because we talk about modifiers. So we know that in addition, it’s a hand of cards. Right? So in addition to having that ace of spades, your other cards matter. But when you have something like a queen of clubs, the other cards matter more. Because it’s really, there’s not such a dominant, we say, mutation in a gene. The other things matter and affect how that works. The moderate penetrance genes more.

Chris Riback: The interplay among them.

Dr. Katherine Nathanson: Yes. Exactly.

Chris Riback: So earlier this year, you and others published a population study of more than 64,000 women in the New England Journal of Medicine. You analyzed the data from the CARRIERS study, cancer risk estimates related to susceptibility. What did you find, and why was it so groundbreaking?

Dr. Katherine Nathanson: So the reason it was groundbreaking was because it actually was a population-based study. So much of our estimates of risk actually don’t come from people in the general population. They come from women who have a family history, who are collected on the basis of family history, or some of the recent studies from women who have had genetic testing. And usually you don’t, maybe not these days, but [it] used to be you didn’t just walk in and get genetic testing. Right? Anybody. And so they were biased estimates. Biased in terms of who was high-risk. So-

Chris Riback: And self-selection of who was going and getting the testing.

Dr. Katherine Nathanson: Exactly. Exactly. And so these were a number of, and I just want to emphasize, huge team of people worked on this project. Really would not have been possible without collaboration. The senior author was [BCRF investigator] Dr. Fergus Couch from Mayo Clinic. I’m on the executive committee after meeting every week for five years, but we got somewhere. But the people who ran the studies and the most important people who collected samples from patients, and the patients who contributed to those studies. So hugely important. You can’t do it with any aspect of that.

So the point was that these were very large, mostly older women, who had breast cancer, who either actually were followed prospectively and then got breast cancer. So there is some cohorts of studies, something called the Nurses’ Health Study, where they look at all the nurses and they follow them prospectively over a number of years. And then some of them get breast cancer, for example. And those studies are very helpful to understand, if you’re in the general population, what’s the risk of these mutations in someone who doesn’t have a family history or doesn’t present to a high-risk clinic. And so that’s actually why it was particularly important. And not surprisingly, it showed that people with a family history have a higher risk of having mutation.

So, the idea was that we found that women with breast cancer from the population, about 5 percent of women overall, and mostly these were older women, had mutations. Whereas about 1.5 percent of women without breast cancer had these mutations. So it was significantly more frequent, but not high numbers, right, of women. And then we were able to identify what the risk associated with each of these mutations is, or mutations in each of these genes, I should say, more accurately is. And I think, actually, I’m going to tell you what I think is really important about this study, which I think is very hard to get from the news coverage.

Chris Riback: Yes please.

Dr. Katherine Nathanson: So I think that there are two parts that are very important. One is, this is 3,200 cases and 3,200 controls. Despite only five genes overall were significantly associated with breast cancer risk. So the number, actually, of genes wasn’t all that high. Now there are some additional genes, if you looked at ER-negative and triple-negative disease, that were associated [with] disease. But the other part is that we routinely have women who are getting these huge gene panels for breast cancer susceptibility. And many of the genes on the panels were not associated with breast cancer susceptibility in this study. And I think the negative aspect of this is actually really, really important. We really-

Chris Riback: What do you mean by the negative aspect?

Dr. Katherine Nathanson: So for example, I’ll give you a good example. So there’s been a lot of discussion. Are mutations in a gene called MBN associated with breast cancer risk? And there’s back, forth, is it associated with disease? Our study and the accompanying study BRIDGES, which was done in a European group, definitively showed no association with disease. So one of the things that is really important is that especially when you’re looking at these women who are getting, because it’s easy to do the testing, these big gene panels. Some of the genes who are basically ruled out as being associated with risk.

And that, actually, honestly, to me is the most important part of this. Because most of the ones that we associate with risk, we knew were associated with risk. But some of the other ones where some people said yes, some people said no, were more borderline. And we were able to really definitively say these are not associated with risk.

Chris Riback: And I would have to assume that in terms of levels of anxiety, intrusion of hair that may or may not have been needed, I would think. You correct me, please, if I have it wrong. That for years, probably, you had women who would get those results and there was uncertainty and stress, anxiety, and perhaps even more.

Dr. Katherine Nathanson: Right.

Chris Riback: And you were now kind of able to say, “We don’t need to worry about that.”

Dr. Katherine Nathanson: Exactly. And to me, that’s actually in part the most important part of this. That we were able to really definitively show that they are not associated. I think it helps us tell us a little bit about who, although it doesn’t really change the guidelines substantially about who should be tested. That’s important too, like who should be tested. Women with ER-positive breast cancer over the age of 65 should not be tested. And those kinds of things, that’s important too. I think there are another series, I’ll say, of follow-up studies, some of which are out, some of which are not out.

So there was also a study that looked at the rate of mutations in Black women. And one that looked at the rates of compared within the CARRIERS [study] group, the rates of mutations in Black and white women. There were no differences, which is also very important to say. No, the rates, there was some variation within the genes. But overall, there was no significant difference between Black and white women. Very important to say. And we have some studies that are accepted, which are coming out soon, actually looking at the non-, what I call the lower cards, but the polygenic risk scores. And how the polygenic risk score looks in this dataset, how does it influence risk.

It’s clearly much more important in, as I said, if you have a lower or a moderate penetrance gene than it is if you have a high penetrance gene. So those things are important. And looking at the rates of mutations in women over 65, very important mostly if you have triple-negative disease. Not so much if you don’t. But to my mind, I think that part of the thing that people, for me, as someone who clinically sees patients who get huge panels, having really good negative data is really, really important. Because it helps tell people, we don’t think this is causing your disease. And you don’t need to have surgery, you don’t need to have other kinds of interventions, because we think this is good.

Chris Riback: This has to significantly alter the way one thinks about the personalization of risk.

Dr. Katherine Nathanson: Right. And the personalization of risk, I think, is really, really interesting. I mean, lots of people are very interested in personalization of risk. And there’s lots of ways to approach personalization of risk. So first of all, do you carry a high, moderate penetrance gene? What is your polygenic risk score? So we know that in women with a high polygenic risk score, their risk of breast cancer is as high as someone who has a moderate penetrance gene. If you have a low polygenic risk score, one of the things that they’ve thought about is decreasing mammographic screening in women who have low polygenic risk scores. Very hard in the US, particularly, to de-escalate things like that.

But it is definitely something that I think, in other countries, may happen. That if you have a low polygenic risk score, a low score, low risk of breast cancer, you may de-escalate or decrease screening. So you think, now we have genes. The genes and the variants sort of affect each other. So they’re not independent. Mammographic density is a known risk factor. Obviously things that we also think about, smoking, alcohol, physical, all those kinds of things are risk factors. And even within genes, the different mutations don’t all have the same risk. And so there’s lots of ways that people are thinking about how can we better personalize risk. But I think the thing that we have to think about along with personalizing risk, is what are we going to do with that personalized risk? Do we feel comfortable, if we say someone’s at a really low risk, saying, “Well, you need less mammography.” I think that’s something, as a…

Chris Riback: Yes. Very hard to do.

Dr. Katherine Nathanson: Very hard to do. These are complicated questions I don’t have the answers for.

Chris Riback: Yes. Well the complicated questions, you understand, doctor, are your fault.

Dr. Katherine Nathanson: Right, exactly.

Chris Riback: If you had to participate in these studies, we have simple questions and very unclear answers. Instead, we’ve got a couple.

Dr. Katherine Nathanson: Well, yes. I mean, it’s complicated questions.

Chris Riback: The complicated questions. You mentioned a moment ago some of the either currently ongoing or potentially beginning studies. And I believe, and you correct me, please, if I have this wrong. That one of them is one that you and your team are launching around a study of very high-risk women with early-onset breast cancer, to identify more about what drives the risks of breast cancer in these women. Do I have that right?

Dr. Katherine Nathanson: Yes. So we know that, even though we’ve done this large study, we know there are several things that are probably some rare, identified variants that are associated with disease. Now those could come in several flavors. So is it possible that there are additional breast cancer susceptibility genes that are rare and unidentified? Definitely possible. But you need to really look at very high-risk women who have been screened negative, and that’s something that we’re interested in, or doing, I should say. And I think that the other thing that we’ve also thought about is, there are some limitations to the way we currently look at the known genes.

Technological limitations. They’re not state-of-the-art changes over time. I think that’s really important. And so, are there variants in those genes or associated with those genes that might be associated with risk that we’re missing? Which is definitely possible in women with breast cancer. And so, that’s something that we’re also interested in looking at. And we were starting to do something called whole genome sequencing. So not just looking at the genes, but looking at the sequences between the genes to see if there is variation that might potentially be associated with risk. There are also what we call rearrangements.

So we know, for example, in BRCA1, that if you think about it like a sentence, you can have misspellings in the sentence. But you can also have missing words or missing phrases. And so, we’re very good at getting the misspellings. We’re pretty good at getting some of the missing words. But sometimes we’re not so good at getting the large phrases or rearrangements. Or if they’re, for example, between the words or something like a comma. How far can I take this analogy, right? That we don’t pick those up so well. So we’re looking to see if some of the families have variants that are associated with that. Those are harder to prove as being functional, so that’s one of the things that we think about.

Chris Riback: How did you come to focus your work so significantly on high-risk women? And I know you deal, as well, in other types of cancer. But in high-risk areas, is what I have taken.

Dr. Katherine Nathanson:  Oh sure. So I’m a geneticist. So I decided very early in my career, actually when I was in medical school, that I wanted to go into genetics. I was always fascinated by genetics growing up, and I thought it was really interesting. And I decided in medical school to go into genetics. So I’m actually double-trained in internal medicine and clinical genetics, which is wild, still. Pretty unusual. There’s probably less than 50, maybe less than 100 people in the country.

Chris Riback: Wow.

Dr. Katherine Nathanson: And so, then when I decided to, I trained in genetics. I did research training. And so, I ended up doing cancer genetics for a variety of different reasons. And that’s where I’ve sat ever since. But I really approach it or come to it from someone who’s really trained as a geneticist, rather than an oncologist kind of perspective. So I’ve been doing it a long time. And my clinical practice actually deals with a lot of other hereditary cancers, as well. So that’s-

Chris Riback: And there are two. So first, fascinating to me that even as a kid, genetics was what interested you, drove you. So, it was never going to be opera singing or—

Dr. Katherine Nathanson: Oh God, no. You wouldn’t want that.

Chris Riback: So as well, there’s an intersectionality as I’m learning about you and reading about you, that you do. One is, you just talked about it. The translational medicine. You run a lab, but you also see patients. In addition, you don’t focus, it seems, on just one type of hereditary cancer. You focus on several. Are there learnings? Is that just because you get bored easily? Or are there learnings and insights that you gain from?

Dr. Katherine Nathanson: So I would say, it isn’t because I get. I think it’s more historical. I sort of ended up doing lots of different things for various historical reasons. And I’m actually doing things that are a little different now, because I’m very interested in really trying to improve genetics generally. I think we really have to be prepared for genetics for everyone, and that’s something that’s really important to me. I have found in my science, however, that you never know what you’re working on comes back to what you were working on before.

I think the biggest analogy, I worked on, actually, a study that actually has led to a drug, down the road, but for renal cancer. But part of the study, all of a sudden we found BRCA1 in this study of renal cancer. And it has to do with DNA damage, and it happened to be important there. And I thought, my God, I try to do whatever I do, and it sort of all comes back together. But it is important. I see neuroendocrine tumors, and one of the things that’s really happening clinically to me is that people are getting these big panels. They get mutations in a gene called SDHA. SDHA is associated with pheochromocytomas and paragangliomas, but all the women that I see have breast cancer, and they got this big panel.

So we’re now trying to figure out and make sure. They don’t think it’s associated with breast cancer, but we’re doing some large-scale studies to make sure that I can confidently tell a woman who comes in with SDHA that that’s not associated with the breast cancer risk. So I feel like it all links back together, because I can do that, because of all the work that I’ve done on breast cancer already. And I want to make sure that I’m counseling my patients appropriately. So I feel like it all seems to intersect and come back together on some level.

Chris Riback: Yes. It seems like it. And I would be remiss if I didn’t ask you. What role has BCRF played in your research?

Dr. Katherine Nathanson: As I say, I will tell this to anybody. BCRF has been the most important thing to my research. I had a difficult early career for lots of reasons, but BCRF provided funding for me at a critical juncture in my career. I would not still be sitting here doing what I do if it wasn’t for BCRF. I absolutely feel that that’s true. I feel like they have been incredibly important over my career in terms of the support that they have provided. Like when I was an assistant professor, sort of struggling, and now, I mean, I don’t think of myself as that much. But now I have a deputy director of a cancer center.

Chris Riback: Now you’re a big poo-bah, yes.

Dr. Katherine Nathanson: And I wouldn’t be there if I wasn’t for BCRF.

Chris Riback: Well, we all benefit from the work that you do. Thank you for that. Thank you for taking the time today with me.

Dr. Katherine Nathanson: More than happy. It was great.

Because certain genetic mutations are linked to a significantly higher risk of breast cancer, developments in screening have both highlighted high-risk groups and added to the broader medical understanding of inherited risk factors.

How can testing data encourage prevention and agency without amplifying personal fear? What can research reveal about genetic markers of risk and predisposition? Or, put differently, how can understanding one’s inherited risk improve approaches to precision prevention?

Dr. Ephrat Levy-Lahad is on the forefront of this research, focusing on breast cancer–associated genetic mutations among various populations, including Arab and Ashkenazi Jewish women. She is a professor of internal medicine and medical genetics at Hebrew University and director of the Medical Genetics Institute at Shaare Zedek Medical Center in Jerusalem.

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Read the transcript below:       

Chris Riback: Dr. Levy-Lahad, thank you for joining. I appreciate your time.

Dr. Ephrat Levy-Lahad: Thank you for having me.

Chris Riback: Before we get into the specifics and the various studies that you’ve released, particularly one last year , I’ve read a line of yours that I really think sets the stage for this conversation. Actually, two lines. One I read where you said, “Knowing your inherited risk is about precision prevention.” You’ve also said you meant it in the context of breast cancer and breast cancer prevention, “Knowledge is power.” What did you mean by those two statements?

Dr. Ephrat Levy-Lahad: So the first statement about precision prevention is really a spinoff I would say, or a take-off from precision medicine. We hear a lot about precision medicine, and mostly in the realm of oncology in general and breast cancer in particular, where you’re looking for a therapy that’s tailored to the patient and to the patient’s tumor. And that’s usually done using genetic and genomic tools by looking at the genetics and genomics of the tumor. What’s really powerful about genetics, and that’s where the knowledge is power, is if you know about the genetic risk before you ever get cancer, what you can really do is precision prevention. So prevention that’s tailored to the fact that you’re at high risk because of a genetic inherited mutation.

And by knowledge is power, what I mean is that there are now very effective means of prevention. So if you have a woman who’s at very high risk of getting breast cancer, there are things she can do to substantially reduce her risk. But if she only finds out about it after she has cancer, it’s not too late, but it’s one cancer too late. And so that’s what these two statements are about.

Chris Riback: Yes. And in terms of that precision, really customizing some of that prevention per the individual. I know that various types of prevention can be that specific down to the actual person. And yes, in terms of some of that data on what that prevention can do, or what that knowledge can do in terms of creating outcomes, I know that some of that was part of what you reported in your study last year. But maybe we could start with genetic testing. How do people react when you talk with them about the importance of genetic testing? Who should be thinking about doing it, everyone, or select groups, or individuals? How do you kind of give broad guidance around the thinking about genetic testing?

Dr. Ephrat Levy-Lahad: I think it’s a moving target. When genetics of cancer started out in the realm of breast cancer—we’re really talking about the mid-90s when BRCA1 and BRCA2 were identified—people were thinking about those tests, mostly in the context of women who have had both breast cancer or ovarian cancer themselves, and had a strong history of these cancers, or people with a very strong family history. Over the years, what we’ve seen happening is that it’s really moved into the realm of the patients. So once a person has cancer or genomic testing of the person and of the tumor, becomes part of their care and management. But where I’m really at in terms of the precision prevention is really trying to get people who are at high genetic risk to be tested before they ever have cancer.

Now, that is also I would say complex. So there are populations where we know that there are very high rates of mutations. So a population I’ve worked on a lot is the Ashkenazi Jewish mutation, these are Jews of European ancestry, and we know that among Ashkenazi Jews, about one in 40 is a carrier of a mutation either in BRCA1 or in BRCA2. And we’ve also shown—[and] all of this work has been supported by BCRF—that approximately half of carriers don’t have any significant family history for various reasons I can explain later. But the bottom line is that if you only went by family history, you would identify only about half of carriers, even though they’re at high risk.

So there are populations, like the Ashkenazi Jewish populations, where I think our studies have shown that it actually makes sense to test everybody. I don’t think we’re quite there yet for populations where the background risk is lower, but I would hazard a guess that five years from now, I think this is going to become universal. One of the reasons it might become universal also has nothing necessarily to do with breast cancer, it’s just that as we understand more and more about our genomes and genetics, I think it’s going to become part of routine medical care in general, is to know what diseases you are at risk for and what you can do about preventing them.

Chris Riback: Yes. I hope to get to ask you just a little bit about biogenetic ethics as well, which I know is an area of interest of yours. And yes, I am curious, the ubiquity of genetic testing today surely is changing some of those dynamics, not only the ethical dynamics, but also in the knowledge. Right now, I would believe very initial knowledge that laypeople like myself might be gaining around genetic testing, but as it becomes more part of the dialogue and the conversation, it would make sense to me as an outsider why your view of five years, as opposed to 10, might be possible. How do you help individuals balance the fear of results versus that power of knowledge, and the power of knowing genetic testing results early?

Dr. Ephrat Levy-Lahad: I think the balance is obviously difficult sometimes, but the balance I usually talk to my patients about is what, in a way, how you would weigh the so-called bad outcomes, and what weight would you give to them. So one bad outcome is you’re going to know that you have a mutation, and that is definitely going to cause some anxiety. And there is quite a bit of data that once a woman finds out she’s a carrier, there’s an uptick in anxiety, that actually usually goes down over time. The other bad outcome is finding a cancer late, that you may have prevented. I’ll give the example of ovarian cancer, which is very easily preventable because you did not want to know that you were at risk. And if you look at these two outcomes and you weigh them, you have to decide what works better for you.

One of the big issues we have is that often men and women will find out they’re carriers, will tell only very few of their relatives. So maybe a brother and a sister, sometimes not their mother and not their children. And many times, not their cousins, for example. And I’ve had patients who are carriers tell me, once I told them, “Listen, you need to call your cousin Ruth and tell her that there’s a mutation in the family.” I say, “You don’t have to say you’re a carrier, but somebody, we can do it, or you can do it, needs to tell her.” And she says, “Well, what do you expect me to do? Call her on Jewish New Year’s or Passover? And say, ‘I forgot to tell you that we have this mutation in the family.'”

And when I started out over 20 years ago doing this, I would sympathize with that conflict. But over the years, because I practice in Israel, which is a small place, and I often see those cousins in the end in my clinic, I said, “If next time you call her for Jewish New Year’s and she tells you that she has a cancer that you could have prevented, how are you going to feel about that?” Once you sort of put it in that light, people realize how important it is.

It’s like going for a mammogram. When you go for a mammogram, you’re afraid to go for the mammogram because you don’t want them to find anything and you’re afraid, but on the other hand, what will you do? Not get a mammogram? So I think it’s a battle between your assertive rational self and your fears. And that’s something we confront all the time.

Chris Riback: And maybe some of the data help as well. You published a study last year in JAMA Oncology. Tell me about the differences in life expectancy and the need for chemotherapy for women who found out they were genetic carriers.

Dr. Ephrat Levy-Lahad: So what we did in the JAMA Oncology paper was really ask ourselves that knowledge is power question. Meaning what happens if you know that you’re a carrier before you developed breast cancer, and then you have the opportunity to take whatever preventative measures you want to take, versus if you find out you’re a carrier only once you’ve developed breast cancer. And we even narrowed it down to women who knew they were carriers, but chose not to have a risk-reduction surgery. So as I’m sure many of you know, one of the possibilities for prevention of breast cancer for women who are carriers is to have a [preventative] double mastectomy. And this is something that seems to have great variability worldwide. And in Israel only a minority, maybe about 15 percent of carriers, choose to have bilateral mastectomy. So we wondered whether if they just have surveillance, what is that going to look like, compared to women who find out they’re carriers only after they were diagnosed with breast cancer. And we found that overall mortality was significantly lower in those who had just surveillance.

Chris Riback: Even with just surveillance. So you don’t even have to do the bilateral.

Dr. Ephrat Levy-Lahad: Even with just surveillance, right. So, there was 94 percent survival over five years compared to 78 percent survival. That means 22 percent of deaths for women who found out they were carriers only after they had breast cancer. And the early detection in carriers, who knew they were carriers and were being followed, led to the fact that if they did develop cancer, it was very early stage. And so, most of them, 55 percent, did not need any chemotherapy compared to 80 percent who needed the chemotherapy in the group that found out they were carriers only after they were diagnosed with cancer. So even women who elect not to have double mastectomy really gain by knowing that they’re carriers ahead of time.

Chris Riback: And what has this done in Israel in terms of genetic testing? And maybe you can talk about what is known as the Israeli Health Basket, and the type of testing that’s available just as part of the healthcare system there.

Dr. Ephrat Levy-Lahad: So I would say over the years, I’ve asked myself the question of whether we should really be testing all Ashkenazi Jews. And we sort of took this step-by-step. The original study that we did, which was published in 2014, was we actually try to find carriers who were identified at random, not because they had cancer or because they had a family history of cancer. And the way we did that was by testing over 8,000 Ashkenazi men. So basically, these were unaffected men that some of them, about 10 percent did have a family history of cancer, which is what you would expect in a general population, but they themselves were healthy.

We found the expected rate of carriers, which is about two and a half percent. And then we looked at the women in the families of these carriers, and we found out that they were still at very high risk for breast and ovarian cancer, because at least theoretically, you could think that maybe there are carriers out there who are actually at low risk, but they have other protective factors that we still haven’t identified. But we found that even if you just test everybody, those who are carriers are still going to be at very high risk for breast and ovarian cancer.

Once we found that out, we started doing studies to show if it’s feasible from, I would say, a psychosocial view, whether women will actually want to get tested, how we can provide such testing, because you really need a different kind of model. If you’re testing people who come in because they have a personal or a family history of cancer, you’re doing a 45-minute session of genetic counseling, you’re explaining all the pros and cons, the types of tests they can do, what the results are going to be. That’s something that’s not really feasible on a large scale. And there was a question actually of whether it’s necessary or not. So we’ve done studies to show that in the context of a general screen, you can really shorten the pre-test process even to just written information, without compromising psychological outcomes in the end.

And once we did that, we approached what’s called the Israeli Health Basket committee. So in Israel, we have universal health insurance. It’s provided through four large HMOs, but the government decides what is the minimalist of services, that’s called the Health Basket, what’s the minimalist of services that these HMOs must provide to every Israeli. And they have a committee that sits every year to decide on new technologies, new drugs that are part of this mandatory list of services. And the first time we applied was in 2018, it was rejected in 2018, rejected in 2019. And in January of 2020, it was approved for the Israeli Health Basket for every Ashkenazi woman to be tested for the common mutations in BRCA1 and BRCA2.

As we all know, there were some other health issues in 2020, namely [COVID-19]. So really it’s just getting off the ground now in the middle of 2021. And I hope that in a year or two, we’ll have some more information on how that’s actually playing out. It’s not considered a national screening program. There is no, I would say, active encouragement yet of women to come and be tested, but all Ashkenazi women are offered this test.

I will say what makes this population different is one aspect that I’ve already mentioned, is that very high background rate, one in 40, that has a mutation. The second difference is that we’re not doing full testing of the BRCA1 and BRCA2 genes. We’re not testing other genes. We are really testing just specific mutations that are known to cause a high risk for breast and ovarian cancer. And if you look at the genetic tests that are normally done, you’re looking at tests that sequence the entire sequence of BRCA1 or BRCA2, or do an entire gene panel. And there are all kinds of issues there about the different types of mutations and the different types of variation that may actually not be disease-causing.

So doing a more expansive genetic test also creates new conundrums in terms of understanding what the variants do. And Ashkenazi Jews were really keeping it simple. We’re just testing for those specific mutations. But still, I think it’s extremely valuable because it’s really a paradigm for the way forward, because ultimately we’re going to know a lot more about variants and we’re going to know which ones are disease causing and which are not. And this will give us a lot of information about how we can actually take the genetics and bring it to the population level.

Chris Riback: Yes. It’s occurring to me as you’re talking, what an incredible, and first of all, what an advancement, but additionally, what incredible data you’re going to get. I mean, it’s just an incredible amount of information that surely will be helpful in all sorts of new ways. Speaking of which, my understanding of some of your current work involves, maybe not exclusively, but two related projects: the Israel Breast Cancer Study and the Middle East Breast Cancer Study, which you’re doing with two other BCRF colleagues. Tell me about each of those.

Dr. Ephrat Levy-Lahad: So the Israel Breast Cancer Study started out with Ashkenazi Jews, because that’s [who] was possible to test when we started out, and we’ve now segued into non-Ashkenazi Jews. And the idea there is actually to look at this population, which is really under-studied. A lot of the information we have in genetics is about Europeans and whites, and Ashkenazi Jews, which are very, I would say, well-studied group in general in genetics. But we know that if we want to really understand the genetic underpinnings of disease, we really have to look for much more diverse sources of genetic information. So if you look at, I would say, almost any field in genetics and genomics today, there is a big push to study populations that haven’t been studied yet, because they harbor a lot of genetic variation on which we don’t have sufficient information and knowledge.

So I would say in that sense, both the Israel Breast Cancer Study and the sister project, the Middle East Breast Cancer Study, are doing that. The Middle East Breast Cancer Study is in collaboration with Dr. Moien Kanaan from Bethlehem University and the Palestinian Authority, and with Dr. Mary-Claire King, the mother-god of all breast cancer genetics from the University of Washington. And we’re really looking at Palestinian women with breast cancer, again, with the aim of capturing that genetic diversity.

An interesting thing is that in that process, in the Middle East, both in Jewish families and in Palestinian families, we often have relatively large families that are in a small geographical area that we can reach. And so we have many families that are so-called “unsolved families” in the sense that there are families with multiple cases of breast cancer, but the genetic cause is not yet known. So part of our efforts are trying to figure out what is the genetic cause in these families. I know it, and it still amazes me every time, is how you can study a specific or a smaller population, and you can still gain insights into questions that are much larger and that affect women worldwide. So, I’ll just give an example from the Palestinian Breast Cancer Study.

Chris Riback: Please.

Dr. Ephrat Levy-Lahad: We found out that about 1 percent of all breast cancer families in the Palestinian population have a mutation in a different gene, it’s called TP53, and generally mutations in this gene cause a very severe cancer predisposition syndrome that’s called Li-Fraumeni syndrome. And that is actually associated with severe tumors in children, often hematological sarcomas. And when we looked at these families in the Palestinian population that have a bonafide mutation in TP53, we really aren’t seeing any childhood cancers, but we’re seeing breast cancers.

What should we be doing with Palestinian women with these mutations? Do they really need the onerous follow-up and surveillance that Li-Fraumeni children have and adults? And we’re talking about having a total body MRI every year and other tests. And it turns out to be a much more general question today. So, when you’re doing a gene panel testing, you’re not just testing for BRCA1 or BRCA2. You’re testing for often dozens of different genes that are associated with cancer. And certainly TP53 is associated with young onset breast cancer.

But now you have these women who are 50, 60, 70 with breast cancer, no family history, and they turn out to have TP53 mutations. So there’s actually now a whole need for information on what subset of TP53 mutations actually behave differently, do not cause Li-Fraumeni syndrome. And we’ve started doing that just in a specific population, but then you can see how it impacts a much more general question in genetic testing today.

Chris Riback: It’s the nature of science. Questions generate new answers, which in turn so frequently generate new questions, which is what would keep folks like you going, and going, and going. Do I have this right, is it, the work that you’re doing, the largest cohort of Arab women in the world to undergo such testing?

Dr. Ephrat Levy-Lahad: So really the credit for that goes to Moien Kanaan’s team in the Palestinian Authority. And really this is the largest Arab cohort. And it’s been done under very often difficult circumstances. Both geographically, the Palestinian Authority, the West Bank, Gaza, movement is often difficult. Also, cultural difficulties. Genetic testing really wasn’t available before the Middle East Breast Cancer Study started. There was a lot of suspicion and worry about genetic testing in adults in the Palestinian population. So, I think Dr. Kanaan and his team have really made a huge difference there. And the BCRF by supporting this study has actually created a service that wasn’t there at all to begin with. And that’s been one of the really gratifying aspects of this project.

Chris Riback: Yes, I would assume so. Now, you also are active in bioethical aspects of genetic research, we touched on it earlier, and I realized that you could do an entire lecture series on this topic. But I’m curious what you might see as the primary bioethical aspects today. I mean, we have a ubiquity of home gene testing, as we discussed. We have massive advances in gene editing. We have privacy and knowledge gaps. What areas around this gained your greatest focus?

Dr. Ephrat Levy-Lahad: I’m going to actually start with the privacy end. I think there are some differences between genetic privacies and other types of medical privacies, but I don’t think the differences are as big as originally imagined. Personally, I think that the emphasis should be on best efforts to keep information private, and I would say this about a lot of medical information, and also nonmedical information. But I think actually a lot of the weight should actually be moved to the downstream, meaning to abuse, or we’re trying to breach that privacy. I think a lot of the effort is made in the safeguards and consent and whatever, and I think a lot more effort should be put into enforcement of any breaches of privacy. I think that’s one way to solve this issue.

And I think the reason for the conflict is because it’s clear that for biomedical research to fulfill its promise, we need a lot of data from individual people. So individuals have to be willing to give their information for this greater good. And if that doesn’t happen, none of us are going to reap the maximum benefits. But it also has to be safeguarded.

If I think about the other aspects, I think gene editing is really a big game-changer in that respect. And I had the privilege of being a member of a National Academy of Sciences committee on gene editing a couple of years ago. And the questions, especially around changing our inherited genetics, what’s called germline gene editing, I think those are going to be very big questions. The situation right now is that I would say on the technical level, it’s not yet safe enough for clinical use. So that gives us time and space to think about what will happen when it actually does become technically safe, because I assume that it will become technically safe. And those are going to be very big questions.

One thing I think in the committee we grappled with a lot and in general I think about, is how do you involve the public in this discussion? And it’s not simple. So the whole idea of I would say scientific advances that have big social impacts, and the political impacts, is you don’t want only scientists making these decisions, or thinking about these problems. But it’s not easy to engage the general public in such questions. And I think things like this podcast, or other discussions, are really important if we want to get to end points that are really maximally beneficial to all of humans.

I think input from the public is extremely important, because the concerns that I might see are going to be very different from concerns that another person is going to have, even in the committee, which was all people who understand gene editing, there were many different viewpoints. That sort of crosstalk is extremely important.

Chris Riback: I’m sure that it would be. Quickly as we start to close the conversation. I’m curious about you. How did you get into this growing up? For you, was it always science? How did you end up in this?

Dr. Ephrat Levy-Lahad: I was always interested in science. In high school, I became really interested in genetics, because I had an amazing biology teacher. Her name was Hannah, and she was just really, really smart. And a lot of my high school classes were really boring, and biology in general and genetics in particular were really interesting. So that was one thing. The other thing I think of all the fields of medicine, genetics relatively has a stronger mathematical component, and I’m a daughter of a mathematician. I could never be a mathematician, but I think that also had some influence.

Chris Riback: Being the daughter of a mathematician might be harder than actually being a mathematician, but that’s a whole other conversation.

Dr. Ephrat Levy-Lahad: And the other thing is actually I would say generational. I’m a woman, and I was really worried about ultimately not having a job or a career that could fulfill what I thought was my potential. And my mother, who is in her late 80s, is from a different generation. And she actually started out in science, and for various reasons, she ended up doing other things. And among that, it’s because I think if you do a straight science career, at the time was more difficult. And my thinking about this was, “I like people. And if I go into medicine, I can still do science, but if the science part doesn’t work out, I will still have a profession that I can work in.” I did not honestly see myself as not having a profession.

That wasn’t my plan for myself. So, I would say in medical school, I was still interested in genetics. I think Israel is really a genetics laboratory. We have so many different populations with so many different diseases and conditions. And when I went to do my fellowship at the University of Washington, what I was really looking towards was to learn basically research tools that would help me understand disease genetics, and bring those tools back to Israel. And I originally did my residency in internal medicine, and my focus was actually adult disease. And my fellowship actually was more on Alzheimer’s disease and I discovered an Alzheimer’s disease gene, but I think that’s one of the reasons I also went into cancer genetics, is even though at the time genetics was largely a pediatric endeavor, I was an internist and I was interested in adult medicine and these are sort of the major adult diseases.

Like anything else in life, there are many instances of chance along the way. And one of them was that towards the end of my fellowship, Dr. Mary-Claire King, of breast cancer genetics fame, moved from Berkeley, California to the University of Washington. And so here was this world-famous researcher in breast cancer genetics, and I started speaking to her and the rest is history.

Chris Riback: Yes. I would imagine conversations, for those who have the privilege to have those conversations, that’s the way it goes with her. And lastly, I know you’ve mentioned it a couple of times, but what role would you say BCRF has played in your research?

Dr. Ephrat Levy-Lahad: If not for BCRF, none of my breast cancer research would have happened. In Israel, I would say the opportunities for translational research funding are very slim, and that is really what BCRF has provided, I think in general, but also specifically for me. All the studies I have described have all been funded by the BCRF, and would not have been otherwise possible. So it’s all BCRF. That’s all I can say. And it’s an amazing organization.

Chris Riback: Well, and it’s just a little bit the researchers like you as well. Dr. Levy-Lahad-

Dr. Ephrat Levy-Lahad: It’s all nature and nurture.

Chris Riback: It’s all nature and nurture, it sure is.

Dr. Ephrat Levy-Lahad: Well, BCRF is all nurture.

Chris Riback: Good. Well, then great for you to bring I’m sure nurture as well, but bring a good helping of nature along with it. Thank you. Thank you for your time. Thank you for the work that you do.

Dr. Ephrat Levy-Lahad: Thank you.

Women of African descent are more likely to be diagnosed with aggressive breast cancers than white women and are more likely to die from their disease regardless of its type or stage. For those living in remote or low-resource areas, limited access to screening and genetic testing make improving outcomes even more challenging.

Dr. Funmi Olopade is renowned for her expertise in breast cancer, as well as her research that has advanced early detection, treatment, and prevention of breast cancer in high-risk women. Her work has focused on many areas, including the role of the BRCA1 and BRCA2 gene mutations in women of African descent.

Dr. Olopade, a BCRF investigator since 2001, serves as the founding director of the Cancer Risk and Prevention Clinic and associate dean for global health, both at the University of Chicago. Dr. Olopade has received honorary degrees from six universities, a MacArthur Foundation “Genius” Fellowship, an Officer of the Order of the Niger Award, among many other honors.

In this episode of our podcast, she talks about her work in Africa and Chicago, the critical importance of precision medicine, and why she’s “impatient” about eliminating barriers to breast cancer care around the world.

Subscribe to Investigating Breast Cancer here:

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Read the transcript below:

Chris Riback: Dr. Olopade, thank you for joining me. I appreciate your time.

Dr. Funmi Olopade: Thank you for having me.

Chris Riback: So in reading about you, it seems obvious to me that we really ought to start with your personal story. Not everyone is the Nigerian-born daughter of an Anglican pastor, MacArthur fellow, tumor-suppressing, gene-finding scientist, associate dean of global health, medical entrepreneur, and by my count, that’s only about 10 percent of what you’ve done in your life? So would you mind starting at the beginning? Where did you grow up in Nigeria, and when did you decide you were going to become a globally renowned oncologist and scientist?

Dr. Funmi Olopade: Wow, that’s a loaded question.

Chris Riback: I know. Those are the only kind I ask, you know?

Dr. Funmi Olopade: Well, this audience is a really important one, because I do care about breast cancer, and I care about all of the work that the Breast Cancer Research Foundation has supported. I didn’t start out wanting to become a famous oncologist. I grew up in Nigeria, went to boarding school when I was 12 years old, and so I considered myself really one of those privileged Nigerians who had the best education that Nigeria could provide. I went to an all-girls school, and then went to the University of Ibadan, where I went for my medical studies.

Now, [the] Nigerian education system was really structured toward the British system. So we had the O levels, A levels, and then you went straight to the university. And I think it was about from three that when you’re 15, 16 years old, that you sort of get tracked into whether you were going to do sciences or you were going to the arts. And I remember toying briefly with the idea of maybe becoming a lawyer. But my parents really wanted a doctor in the family, and growing up as a pastor’s daughter, and on many occasions, I saw my father pray for people to get well, and they didn’t get well. And so I think he really wanted one of his children to be a medical doctor.

So, I happened to be [child] number five of six, and so I would say I went to medical school screaming and kicking because I would have rather done physics or something more mathematical. But here we are.

Chris Riback: Here we are. Is your father still alive, or did he remain alive long enough to see you become a doctor? I’m curious, how did a man of faith feel about his daughter going into the sciences?

Dr. Funmi Olopade: Well, I think in those good old days, history would have it that good people either went into medicine, law, or they became pastors. And so I think they took advantage of the opportunity you had, and was educated by missionaries, of course. And so he went to divinity school, and it was in theology, and he became a pastor. But I think he really was very intellectually curious and always wondered about science. And so I have my siblings before me who went into economics and engineering. And one of my siblings is a veterinary doctor and a nurse. But that was sort of his last hope to become a doctor.

And so that’s why I did go to medical school. And I really appreciated the fact that growing up in Nigeria, where the resources were scarce to actually impact people who got sick, that there was still a lot that was unknown about the human condition. And so, I went to University of Ibadan Medical School, which I still believe remains the best medical school in Nigeria, they really had outstanding faculty who were outstanding clinicians. And we knew the diagnosis for any disease, or at least we thought we knew it, by talking to patients, touching patients, and then really having very broad differentials.

However, when I got to the United States, and I had followed my brother who is a PhD student at Stanford, my option was to start at Cook County Hospital, and that was really when I saw the need for more research to understand cancer, and I became fascinated by cancer research. And so coming to the University of Chicago for my research training and post-doctoral training, I was fortunate to have been in post-doc with one of the best cancer geneticists of our time, Janet Rowley, who was studying chromosomes and leukemia. And at that time, we had the level of resolution of being able to do chromosome preps, caught chromosomes, and looked for changes in chromosomes. And I remember when I went to talk to her in the laboratory, she said, “Oh, no, no, no, this technology is not going to be here for the future. You should study molecular genetics; you should study molecular biology. And then apply that to problems in solid tumor.” Because at that time it was really very hard for us to culture cells from solid tumors.

And so that’s really how I began working in the lab with one of the best human beings who was also a great scientist, generally.

Chris Riback: Yes, and I want to ask you about that in a moment. But before we get there, you passed over how in the world did you end up at Cook County? You talk about challenging resources in Nigeria having grown up and what you saw in med school there. Cook County Hospital, particularly in the ’80s, that was a pretty tough place. You surely saw? everything there?

Dr. Funmi Olopade: Oh, absolutely. And actually, it was really just one of those things that happens to you when you’re young and fully idealistic, and not really thinking much about the world, because I came to visit my brother at Stanford, and then I, of course, wanted to see when I could train at Stanford or [the University of California, San Francisco (UCSF)]. And going for the interview at UCSF, I was told, “Well, they didn’t really take international graduates,” and since, of course, my background from Nigeria wouldn’t have been up to standards for people who are trained here, they gave me the advice of to look for county hospitals, and that maybe if I started at a county hospital, I may be able to work my way up.

I thought that was the best advice anyone gave me. I happened to have had a friend who was in the university with us, but now was going to school in Chicago. So, I came to Chicago I think it was the day after Labor Day that I had my interview at the county hospital. It was a beautiful day, and I got a job right there and then, because of course they were short-staffed, and they needed doctors. Any warm body that was available was hired to come and work at county.

But because I was married and I hadn’t planned to leave Nigeria, I [initially] told them I couldn’t take the job, but that I would go home, get the blessings of my parents, and then consider coming back. But I say that because I really had no idea how cold Chicago was.

Chris Riback: Yes, so I was going to say, I’m very glad, it’s good for the rest of us, that your interview was the day after Labor Day, and not three months later.

Dr. Funmi Olopade: Right, right. And so, as soon as I got back to Nigeria, and I had had a wonderful summer in America. In fact, President Carter had really encouraged Nigerians to travel and discover America. So that was how right after graduating medical school, during my rotating internship, which was what you did before you actually got your license to practice, I then just took off to spend some time traveling across America. And I loved it. It was just totally beautiful. I thought everything was big in America, and while many Nigerians would have opted to go for post-graduate studies in the UK, I just couldn’t wait to get back here.

So once they offered me the job, I thought, “How about starting right after Christmas?” And so that’s how I ended in Chicago in January. I had never seen snow before, and it was kind of really interesting. You read about it, you thought about it, but as the plane landed, I saw the snow on the ground, and I didn’t even know how I was going to walk on it. But here I am.

Chris Riback: Here you are, yes, and it’s funny you mentioned it. Yes, you’re right. It does snow every once in a while in Chicago. And I’m really wondering, should one of us give UCSF a call and let them know what they missed out on, or just should we forget that whole part?

Dr. Funmi Olopade: Well, one of my best collaborators and best friends is Laura Esserman. So, we talk about UCSF all the time. I collaborate with them. I work with them. And it’s just one of those things. It’s really the case that we have different ways of training in medicine, and biomedical research enterprise depends on what you have available in your country. So, I don’t fault them.

Chris Riback: No, of course, I’m just teasing. How significant was it, and how rare was it, that you trained with a female scientist as you did at the University of Chicago?

Dr. Funmi Olopade: Yes, well, it’s really one of those things that I really appreciate about the University of Chicago. At the time that I was looking to join a lab, we had some powerful women who were absolutely fantastic scientists, of course, Dr. Rowley being one of them, Elaine Fuchs, and [the late] Susan Lindquist. And these women were top-notch doing cancer research at the University of Chicago. And Janet said, “Before you settle on a lab, just go and interview a lot of people.” And I can tell you, I interviewed four or five wonderful female scientists who could have been good mentors for me. And it boiled down to choosing whether I would work with Dr. Rowley or with Elaine Fuchs. And Elaine Fuchs, of course, is a famous scientist who is at the Rockefeller. And we see each other now and sort of joke about that moment in time.

And it came down to Elaine saying, “Well, you’re a doctor. I’m just not sure about doctors in my laboratory because I don’t know. It may be just so basic. And I don’t know if that would be a good match for you.” And then Dr. Rowley saying, “Well, I just was having a lot of fun collecting stamps, and my children thought I was doing stamp collection when I was cutting chromosomes and trying to understand chromosomes and cancer.” And I thought, “I am a doctor. I really love being a doctor.” And it probably would be a lot easier for me to begin to think about translational medicine as bringing questions from the clinic to the laboratory, instead of the reverse, where you spend time understanding mechanisms in the lab, and then you said, “Oh, by the way, does it work in the clinic?”

And so that was really what Dr. Rowley [imparted] on us, was that if you really want to solve the problem of cancer, bring a problem from the clinic, get samples from the patient, and then let’s study it in the laboratory, and that really was just an amazing period where we had giants like Dr. Rowley had described chromosome rearrangements in leukemia and in cancer, and now, the next generation of postdocs in their laboratory now needed to find out what were the genes that are in this chromosome rearrangement? What are the genes that are in the deletions? And that’s really how I started looking for tumor suppressor genes because there was a really good model that you will find deletions and then if you mapped the area of deletion, you might be able to come in and find tumor suppressor genes.

So the ’80s really gave us a good foundation in terms of the link between chromosomal abnormalities and cancer, and then the ’90s really we were equipped to be able to clone one gene at a time, figure out one translocation at a time, then go back to the lab, try to find out what these genes did, and then of course, once you identify genes, then you have to look at the function, and then of course figure out whether you can target them for treatment.

Chris Riback: Why do African American women and women of African descent often develop breast cancer at younger ages than Caucasian women?

Dr. Funmi Olopade: So the question about genes and cancer really became “Okay, so what causes all these deletions and chromosomal breaks in cancer cells?” And people are predisposed to getting cancer, and if they are, how do you find them? So that was sort of the other thing that happened in the ’90s, was that as we started looking at tumor suppressor genes, we also had a parallel process where a human geneticist had actually mapped diseased genes to different chromosomes. And I remember a really wonderful collaboration that I had with Mark Skolnick at the University of Utah. He was mapping families at risk for melanoma, and it so happened that it was the same region that I was mapping on Chromosome 9, and that’s why I got really interested in whether they are inherited alleles, inherited mutations that could point us to sort of ways to prevent cancer.

And so while I was mapping Chromosome 9, of course, other investigators were mapping the region for breast and ovarian cancer on Chromosome 17. And the same Chromosome 17 also harbored the HER2 gene that is frequently amplified in HER2-positive breast cancer. And so I became really good friends with Mary-Claire King, who wanted to collaborate to find families with breast and ovarian cancer, and also very good friends with Dennis Slamon, who had actually defined HER2 gene amplification and HER2 gene really becoming very important in breast cancer.

Dennis Slamon did his training at the University of Chicago, and he also had been inspired by Dr. Rowley. So early on in my career, I really ran into him, we did a study together looking at treating women with HER2-positive breast cancer and finding that just by developing Herceptin that could target the genetic abnormality in these tumors that you really had a dramatic response in women who ordinarily would have died within two years of having metastasis. And as you know, the University of Chicago is on the south side of Chicago. I was beginning to see if women come to me because they had a family history. They tended to be young when they develop their breast cancer. And then I also saw African American women, many of them very young, who also came with aggressive breast cancer.

And so that’s how we began to really look at who has HER2 amplification in their tumor that could get testing and then be able to get on a clinical trial to be able to be treated with Herceptin, and then who had BRCA1 mutation because in 1994, BRCA1 was identified, and Myriad Genetics, by that time, Mark Skolnick had started Myriad Genetics. And so they approached me [asking] if I had families that they could test as part of their beta test, and lo and behold, we found some of these young African Americans that we had recruited to our study had mutations and BRCA1, and then shortly after that, BRCA2 was identified.

So that really got me very interested in what’s driving young-onset breast cancer, because the face of breast cancer in Nigeria was that of a young woman. Of course, the population, we didn’t have too many old women in Nigeria, given that the average lifespan was 52. So I really got very interested in trying to understand why young women develop breast cancer, and whether there’s a commonality, whether you were Black or white, and then if there was a commonality, what was that? And that’s what got us really collaborating.

Another collaborator that I still enjoy collaborating with is Chuck Perou. Chuck Perou, too, had come through Chicago. He was, actually before going to grad school, was a technician here. So, I ran into him at a Gordon Research Conference, and we got talking. His sister was one of my colleagues and friends at the University of Chicago, and I was like, “Oh, I know you. You look like your sister.” And then we really started chatting about what he had discovered at the time, which is the gene expression patterns in different tumor types. And so this basal-like breast cancer happened to be really common and very significant for women with inherited BRCA1 mutations.

And so we started really, then, thinking about how we could use gene expression signatures to understand heritable factors for breast cancer. And so, I really began looking for additional genes that were not BRCA1 and BRCA2. So, we did genome-wide association studies, and we were fortunate to get an idea grant funded by the Department of Defense, this was in 1998, because I had this idea that: Is it possible that there’s a link between young women getting breast cancer in Nigeria and African Americans? How much of the African ancestry made you get aggressive young-onset breast cancer?

And so the story evolved, because for a very long time, the conventional wisdom was that these women denied that they had a problem, so it took them a while to get to the doctors. But what we found was that contrary to previous opinion that breast cancer grew very slowly, so you could go in, maybe in Europe, you could go in every two years to have your mammogram, I started saying, “Look, these women, when I talk to them, they will tell you they had a mammogram that was normal last year,” or some at the time, we diagnosed the breast cancer, the mammogram was normal, because there’s some breast cancers that just don’t show up on your mammogram.

And so, I became really concerned that if our recommendation is that when you turn to 50, or if you get to 40, go ahead and get your mammogram, and here we have all these young women getting breast cancer before they were 40, how were they going to get diagnosed early? And so that’s why I really was pushing that we should have more broader access to genetic testing. And I wrote an editorial in the New England Journal [of Medicine] in 1996 saying the only people who aren’t getting tested for BRCA1 are people who don’t understand the biology, because I assumed once we found the gene, and we know what the gene does, that the gene will increase your risk for cancer. To me, it was a no-brainer. Why wouldn’t everybody want to know whether they have that mutation?

But it turned out that the medical community was not ready, and the genetics community certainly had not really dealt with an idea that you should be testing people for adult-onset cancer, right? They’re born with a genetic mutation, but they are not getting cancer until their 30s or 40s. So what do you do? How do you tell them? What are the interventions?

So, I was appointed chair of the ASCO Cancer Genetics Task Force, and I think it was really my background from Nigeria and my training that prevention is better than cure, and we were told that preventive and social medicine was really key. As a doctor, you couldn’t wait to treat cancer. You couldn’t put the patient outside of the context of a social environment. So my medical training really emphasized preventive and social medicine. And so I became a real fanatic in terms of really making sure that we could get other oncologies to adopt the ASCO Cancer Genetics Task Force to make it a business of oncologies to find high-risk families, and to develop interventions to help them so that they don’t have to wake up one day and find that they have advanced triple-negative breast cancer.

And that’s really why and how I got into looking at African American patients and trying to figure out what is genetics, what is poverty, and certainly, Chicago is full of rich Black women, middle class Black women who are police officers, teachers, who are not only living in poverty. And so, the more I see the variety of Black women who are coming in with triple-negative breast cancer, the more I refuse to accept the fact that it was all poverty and their social determinants. And I really wanted to study the biology determinants of aggressive breast cancer.

Chris Riback: It’s so interesting because you started to address what was going through my mind, which is, what was it about you that was driving questions that others weren’t asking? Was it because of coming from Nigeria, your education there? Or was it because you started out as a medical doctor, or is there just a curiosity within you that’s just part of who you are? What do you think encouraged you, inspired you to ask questions that so many others weren’t asking?

Dr. Funmi Olopade: Well, I know certainly, it’s because of my training as a physician. But I also know that if you, as a daughter of a pastor, there are many more questions than answers. And so I think growing up, my father actually really encouraged us to ask questions, because I think he himself must have been baffled about this God that would be afflicting so many misery over human beings, and so I think it started off with really having been brought up to ask questions. And the conventional wisdom was also always the case in our medical school that the British will ask you at your oral exam to give 10 courses of an ailment, and the thing is, you have to think about all the possible 10 reasons why somebody has a symptom. And so by having to think about broad differential diagnosis, my brain, I guess, was trained to always ask, “Okay, what else can it be? Why else should we be looking at this?”

And so I think it was partly my upbringing at home to ask questions, to question God in a way. And then the other part of it is that there’s so many things that were unknown, and I think the scientific method is the only way where you always have to keep asking questions. And so I think that got me to really not always accept that, “Okay, this is the answer,” when we, unfortunately, hadn’t even asked the questions.

And so when I was at Cook County Hospital, there was always the case, when people died, of wanting to know why did they die. And so in my medical school, we always wanted to get an autopsy, because of course, we didn’t have CT scans, and we didn’t have all of those things. And so when I was a chief resident at County, one of my duties was to make sure I met with families, and I asked them if it would allow us to do an autopsy. And that year that I was chief resident, I think our autopsy rate was probably about 70 percent, because when you explain to anyone, even when they’re grieving, that, “Look, you’re going to help us learn about your family member that just died,” most people would say, “I give consent.”

And so, at the University of Chicago, and when I also talked with my colleagues who think that black patients or African Americans don’t want to participate, that was never my experience. My experience was that they wanted to be part of the solution. They wanted to be part of studies. There was never a patient of mine that I asked to consider a clinical trial who didn’t say, “Okay, sign me up for it.” And so I felt like there’s a trust that the community had in me to ask questions and to help them find solutions. And so that was really my motivating factor was that I’m from this community, this community has a lot of questions, and how come no one is studying them?

And so it became a personal passion of mine to actually do cross-continental research, because I also went to school completely free of debt in Nigeria. In fact, Nigeria, I’m given a scholarship, a bursary, to just enjoy my time in medical school. So I feel like I had to help contribute to scientific advances in Nigeria. So as soon as I was able to do that, I started collaborating with former colleagues and collaborators in Nigeria. They taught me a lot, and I taught them too, and it became a really mutually beneficial partnership to do this cross-continent collaboration.

Chris Riback: And are those the clinics that you have opened and started? And maybe you can tell me about that. My understanding is the first one was in Nigeria? And there’s progress from there. So tell me about the clinics that you’re offering in Africa?

Dr. Funmi Olopade: Yes, so the good thing about what has happened is that we now live in a global village. There’s direct flight from Atlanta to Lagos. And so in 2004, we had a meeting of professional women in Lagos, and we wanted to ask their opinion about, “What should we be doing, how should we be advancing some of this work that I am now able to do by collaborating with investigators in Nigeria?” And they had a communiqué at the end of our workshop. It was a 10-point communiqué, where they encouraged us not to just take samples out of Nigeria, but to actually build capacity.

So we, of course, realized the majority of women that were developing breast cancer in Nigeria had estrogen receptor-negative breast cancer. This is the most aggressive type of breast cancer. And it was 70 percent of them that had that. And that had never been reported in any medical journal. So when we tried to publish it in the Journal of Clinical Oncology, [their] thought it was, “Oh, it was just bad fixation. We just didn’t do the correct experiment.”

Chris Riback: Because why, because they couldn’t imagine the numbers could be that high?

Dr. Funmi Olopade: They didn’t imagine the numbers could be that and so after we studied the first 300, it was just not acceptable. So then I went to Senegal to collaborate with pathologies there, and we went to Cameroon, and then we went to Uganda, and what we really wanted to do was, “Okay, what’s going on? Why are these young women across these sub-Saharan countries getting breast cancer, and when they get it, they get it at a very young age, and they get estrogen receptor-negative breast cancer.” So that just turned everything on its head.

And then because many of these patients, when we then ask them, after they’ve given us their samples, and we’ve studied them, and then we wanted to ask about the follow-up, and we will be told, “Well, they came in, and because they couldn’t afford treatment, they went back home, and they were dead. And we couldn’t get follow-up because they were dead.” And the soldiers who were working with us were frustrated, because most of the women presented in advanced stages. Then we started sending out students, we got a grant to bring doctors here, and we realized that in fact, these women were showing up, they were so young, some of the time, they had just had a baby, so even when they showed up in the doctor’s office, or in a community health center, they were told they had a boil, they were told they had an infection. They were given antibiotics, and they had no idea they were dealing with breast cancer.

And so we then thought that the onus was on us to now raise awareness about the fact that there’s a change in demographics. Women are no longer dying in childbirth. Women are no longer dying from infectious complications. In fact, women are now getting breast cancer. And that demographic change is happening all over the global south, all over Africa, all over Latin America.

And so because we have been so successful in helping women survive, now we have this burden of chronic, non-communicable conditions. And so, in a country where people were not even thinking that breast cancer was a problem, doctors were not even trained. There was no word for breast cancer in Nigeria when we started our work. And so we then felt that it was really important, getting these women professionals who were on top of their game, who were now part of the health systems, who that were now part of the government, who were now in industry, and they all gathered together with market women, and they said, “Yes, we’re not dying. We want you to think about how to diagnose cervical cancer, how to diagnose breast cancer. And yes, we also want to participate in BRCA research,” right? Maybe women also have BRCA1 and BRCA2 mutation, we want access to that as well, because we want to use it for prevention.

So that’s how we started now training doctors to now be able to start our cancer risk clinic so they can also offer these women genetic testing, and then of course, we kept pushing and asking, and we were so fortunate to have funding from the Breast Cancer Research Foundation who then said, “Oh, we’re going to fund your work in Nigeria. And not only are we going to fund your work in Nigeria, we’re going to help you access drugs to treat these women in Nigeria because we’re going to help you develop a clinical trials platform.” There’s one thing is to do genetics research, to do epidemiology research, to know so many things that were going on, but a different thing to actually say, “We’re going to put money to treat you so you have a chance to survive.”

And so, we’re on our second clinical trial now, partly aided by money that we were able to raise in the US to buy drugs, to rush pharmaceutical company to give us drugs so we can treat women and have the opportunity to cure many women. The first clinical trial we did was for Xeloda®. It’s an oral medication. And when we started, we thought, “This will be really great. These women come in with triple-negative breast cancer. We give them a pill, and the pill melts their cancer away.” How remarkable would that be? And that study, we couldn’t finish it because we were looking for women who did not have metastasis. And for 25 years, we could not find enough women who were not showing up with metastasis.

So we closed that study, and then we went back to the drawing board, just trying to understand why is this cancer so aggressive in these women? Why couldn’t we find women that were picked up at an early stage? We did the same in Chicago. We started saying “Why these cancers are presenting so aggressively?” And that’s why we started using MRI to screen these women. And instead of asking women with BRCA1 to get MRI once a year, we started saying, “Maybe we should be doing it twice a year,” because these cancers are presenting as interval cancer, and we learned a lot, because some of these women came in and they didn’t want to have bilateral mastectomy. They wanted another option. They wanted us to push prevention instead of just offering bilateral mastectomy to them. And I certainly learned a lot from these women. And you know Chicago, it’s Polish women, it’s women from Ukraine, it’s African American women. It’s everything.

Chris Riback: Yes, it’s an incredible melting pot.

Dr. Funmi Olopade: Right, it’s a melting pot. It’s everybody. And then as our clinic got more famous, we had people fly to us from all over. And some of them, because they were so used to plastic surgery, no matter what I told them, they were going to have both breasts removed and have plastic surgery. And then on the other hand, I went back to Cook County Hospital, and I would tell them, “We should do prevention,” and my African American patient had said, “Oh, you know what, we’re not into that yet. We have so many other things to worry about, don’t put this additional burden on us again, because we’re healthy now, so why would we be taking our body parts?”

And so that’s why I really felt like we can learn from our patients, and patients come in diverse shapes and forms, and my job as a doctor is to be able to meet patients wherever they are, whatever they need to do, and then what we don’t know to study it.

Chris Riback: Indeed. In preparing for this conversation, I watched a 2009 video that you did, and in it, you said virtually the same thing, and it was remarkable when I listened to it, but now I’m hearing your philosophy and more of your approach, and really you redefined what it means translational. Translational for you is not just you connecting the lab and the medical office, it’s connecting continents, and I hear the lessons and the through line of your story and what you’ve learned. But in that 2009 video, you said, “My patients are my best teachers.”

Dr. Funmi Olopade: Absolutely.

Chris Riback: And you still feel that way?

Dr. Funmi Olopade: Absolutely, absolutely.

Chris Riback: Yes. The work now, extending your research, the genomic biomarker-based oncology clinical trials, what’s next on that work?

Dr. Funmi Olopade: Oh, we’re really very excited. Of course, now, we have a pandemic, and we’re all sort of shut down. And now we’re thinking about what does this mean for health equity, and of course, we also have the Black Lives Matter [movement] and sort of the social unrest around social injustices. And so, one of the ethical frameworks that I’ve always used as a geneticist is that you really have to think about social justice. If you’re born and you have a genetic mutation, the onus is on us to help you live the best life possible. And so when I am offering genetic testing, and when we first started, the first women who came to me wrote a check for $2,500 and said, “I’m just curious, I want to know,” and by knowing that she had a BRCA1 mutation, she saved the life of every woman and man in her family, because she was proactive. And she wrote that check even at the time when our medical community said it couldn’t be done, and it shouldn’t be done.

And I learned a lot from that woman. And I was thinking, “How about that woman who has the same risk, but is totally unaware of it, is not educated enough to know about this,” or, doesn’t have the resources.

Chris Riback: Doesn’t have the $2,500 to write the check.

Dr. Funmi Olopade: Right, doesn’t have the $2,500 to write the check. What is my role, as a healer, to reach out to that person? How do I use my voice as an advocate to make sure everybody has a chance?

And so that’s why I tend to work with a lot of advocacy groups. And my patients, I remember the first time that a patient of mine went to Springfield to lobby the Illinois state…

Chris Riback: Yes, the state capitol in Illinois. Yep.

Dr. Funmi Olopade: … the state capitol in Illinois to say, “We have to cover genetic testing.” And it was compelling. My former governor was the first to approve genetic testing for patients on Medicaid because it just doesn’t make any sense that because you don’t have insurance, you cannot have the same access to genetic testing that somebody with a third-party payer or with money has. And whether it’s passing privacy laws, or I also remember going to then Senator Obama at the time when he was first appointed to the Senate going to work with his staffers, that we have to have precision medicine. And a lot of people would say, “Oh, precision medicine is going to take money away from what we should be doing about social determinants.” But I knew how patients who came to me from northern Indiana, at the time when we had clinical trials for Herceptin, lived because they were able to get the test to find out that they had HER2 gene amplification.

And that was a game-changer for me, was that these patients in northern Indiana, they just happened to think about coming to the University of Chicago, they were Black patients, and they got into the clinical trial, and now, what would have been a sure death for them, came out of there alive, because they came to the University of Chicago. And so not everybody in Chicago can come to the University of Chicago. But our best practices can be disseminated into the community, and we can partner with community doctors. We can accelerate the time it takes to get us to get these advances to everyone.

So, if there’s a cure for breast cancer, our goal is to make sure that everyone in a global village knows about it and can be part of new treatments, a movement to get women to live longer. I go back to when I first came to this country, it was [during] the AIDS epidemic. I was at Cook County Hospital, and our patients were dying. They were dying by the numbers. We didn’t even know what was going on. But then, there was a whole idea around solidarity. And now we know that HIV/AIDS, we can eradicate it with developing vaccines. We have a cocktail of drugs.

The same thing, we should be thinking about cancer research as research that we all have to participate in—it doesn’t matter where we live, whether we’re in Nigeria, in Bolivia, anywhere we are in the world, there’s knowledge that can be created. And so my goal is that precision medicine means precision medicine. We need to study every patient, everywhere, so that we can find the right drug for the right patient at the right time, and that’s why I’m in a hurry. I’m impatient about how we have really been negligent as a scientific community in terms of helping to eliminate the barriers. The inequities are just unacceptable to me.

And so this moment, we have a pandemic, and we know without testing, people are getting infected. So how about testing, testing, testing, to personalize cancer care?

Chris Riback: Well, it’s clear that this is a moment that you have come to naturally, and the totality of your experiences, and you’re the daughter of a pastor, and the Nigerian education, and starting professional life as a medical doctor, but then your research and the experience, and the clear love that you have for Chicago and the U.S. and the people and the world, and the fact that you took a chance on this guy, Obama, I’m not really sure he’s going to become anything. I kind might be wasting your time there, but okay, you make your own decisions. If anyone is going to be able to push testing, testing, testing and cancer and push us towards a cure, I think I might have put my $2,500 check, and maybe even a little bit more on you.

So thank you, thank you so much for the work that you do, and for taking the time to tell me about it.

Dr. Funmi Olopade: Thank you very much it’s been a really wonderful interview, and I’ve enjoyed talking to you. Thank you for what you do.

While genetic testing and counseling for breast cancer has been available in the U.S. for many years, accessing these services in Mexico and the rest of Latin America is more challenging due to limited resources. This disparity is particularly concerning because hereditary breast cancer has been found to be a serious problem in this population of women.

Leading genetics researcher and oncologist, Dr. Jeffrey Weitzel, has devoted his career to decreasing these barriers. He led a groundbreaking study that revealed BRCA mutations may be present in 25 percent of U.S. Hispanic women, leading to calls for increased genetic testing and counseling.

Dr. Weitzel, a BCRF investigator since 2013, is director of the Clinical Cancer Genetics Program and professor of oncology and population sciences at the Beckman Research Institute at City of Hope. Dr. Weitzel is pioneering low-cost genetic screening materials and training doctors and nurses working with underserved populations in Peru, Colombia, and Mexico.

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Read the transcript below:

Chris Riback: Dr. Weitzel, thank you for joining me I appreciate your time.

Dr. Jeffrey Weitzel: My great pleasure.

Chris Riback: There are so many places a conversation with you could go and I certainly hope that we get to go to all of those places or at least most of them. I’d like to start with your work that centers on improving access to genetic screening and breast cancer prevention in Latin America and Mexico. Let’s start perhaps with a laying of the geographical land. How big is the screening and prevention problem in Latin America and Mexico?

Dr. Jeffrey Weitzel: I don’t think we have to go beyond our own borders to get some sense of that as well. Really, our project is about, started at its heart, to address disparities. I’m an oncologist and a geneticist so this onco-genetics realm. Certainly there are many BCRF projects that relate to the causes of breast cancer. People come to mind like Dr. Mary-Claire King and others who are just absolutely stellar leaders in identifying hereditary forms of breast cancer.

While it’s not the most common cause of breast cancer it is perhaps the most impactful. The risks are so extraordinary that people really deserve to be identified and given guidance as to how to take care of their risks. So, over 20 years, it’s been over 20 years that we’ve been able to do commercial gene testing for breast cancer pre-disposition that there are still groups that are left out in the United States.

This really goes to my own back yard. I’m living in Los Angeles and we have a very rich Hispanic fabric. A lot of people with ancestry that might originate in Latin America. This goes back to the year 2000 and to one of my dear colleagues. If you don’t mind, I’ll tell you a story.

Chris Riback: Please.

Dr. Jeffrey Weitzel: Dr. Feldman was the chair of oncology at one of our safety-net hospitals. This is one of the LA County hospitals. 89 percent of their indigent service population is Hispanic and or has Spanish language as even their first language. She came to me when we were at a breast cancer retreat talking about science and she said, “We’re dying out here. I have 32-year-old women coming in with easily palpable stage-three breast cancers, and they have a family history of breast cancer. Why weren’t they identified, given access to genetics and the opportunity for prevention.”

This is something that’s so obvious. We know the story. We know what hereditary breast cancer looks like but these people weren’t getting access. So, I said well, let’s look at that. We literally created an infrastructure right off the bat. We’re going to open a free clinic, we’re going to provide the care but we still have to figure out how to get the testing done because in those days the test cost 4,000 dollars for two genes. Medicaid did not provide coverage for testing.

First, we had to say okay, what do we need to do special for these individuals so that we can make them feel comfortable. If you build it, will they come? If they come, will they learn? If they learn, will they do the right thing? If they do the right thing will they be free of cancer and live longer.

Chris Riback: Was that conversation the inspiration for you for your groundbreaking study that revealed the BRCA mutations may be present in 25 percent of US Hispanic women? Is that what drove you to do that research?

Dr. Jeffrey Weitzel: This is the thing, when you go to do the right thing, sometimes you learn other stuff. So, again from a friendship level we started this program to address a disparity. I’m honored that I also have Conquer Cancer professorship in breast cancer disparities in part because of this legacy. But we first published on the beliefs and interest in risk-assessment in Latino cohorts we said, if you build it will they come? We literally put that in the title. We started the clinic and said, are people coming in? Are they learning? And they were.

By hook or by crook we got funding and created our own funding to try and get testing done and in the process we discovered that, wow, these people had a high prevalence of mutations, this is in our study, just at the county hospital, which we published on in 2005. Further, we saw the same mutation repeatedly, which suggested a population level impact of history, anthropology, and epidemiology.

I’ll tell you more about that story in a moment, but we, kind of, through the backdoor, learned the epidemiology and that’s because nobody else was taking care of these patients. So what happened in the intervals, I have a large research network. This is something I’ve built over 25 years. I have 39 sites in the US and now we have 7 in Latin America. We’re all running the same protocol, which is everybody we see for risk assessment we enroll and we study.

The 2013 paper that you’re talking about, which at that point was published in the Journal of Clinical Oncology which is a high-level journal because it was a novel observation of 746 individuals, all of whom had breast cancer, presumably at a young age they met the criteria for testing and we got testing and it represented mostly Mexicans and Latin Americans and Central Americans based on our service area.

Chris Riback: Was it that 52 percent of them had the same mutation? I might be getting the fact wrong. What was the data there?

Dr. Jeffrey Weitzel: Of all the women with breast cancer 25 percent had a mutation. Of those mutations we found that there were two specific mutations in BRCA1 that had counted for a large proportion of cases and then multiple other mutations were seen. One of the things we discovered, because this was work I did again, on this initial cohort from the county hospital. First we found a bunch of mutations, then were new technologies coming along which was to look for specific mutations that couldn’t be detected by just sequencing.

They’re called large genomic rearrangements. So, big dilutions. Ironically, you can find a misspelling in the gene very easily with sequencing but if a whole chapter is missing, you don’t see that, because everybody’s got two copies. One copy is normal. One copy is not. You’re just reading through and you think they’re all normal but they’re actually just completely missing that stuff.

It turns out that we were one of the first observations of a large genomic rearrangement, so a very specific type of mutation that was repeating in this population, had never been reported in Spain or any other country. So, we surmised that this was what we call a founder mutation. Any geographically or culturally isolated population can have this.

We further went and found out that not only was this frequent in the population, it looked like it was in Mexico. We found it once in Venezuela but it turns out that individual was Mexican. It turned out to be exclusive from people who originated in Mexico, and it was frequent. We did what we call haplotyping to determine how old the mutation was, kind of like carbon dating, and we found out it was 1,500 years old.

This long predated the colonial Hispanic influences. So the colonial influence of the Spaniards, et cetera, and really reflected origin in an indigenous population, indigenous American population likely in central Mexico.

Chris Riback: Not brought from Europe.

Dr. Jeffrey Weitzel: That’s right. Now we found a lot of other mutations that were frequent. So the other one that was a very interesting observation we first published in 2005, one of the first times it was documented, was multi-generational Catholics, we found the 185delAG mutation of BRCA1 which is a known Jewish founder mutation. What we published on then, in 2005, was that they shared the same chromosome as my Jewish patients from West LA.

This shows an ancestral origin and that links it immediately to history and to anthropology. This is where I get just completely excited because we start talking about the impact of history and humankind and the consequences of diasporas. Think the Spanish Inquisition, 500 years ago, It’s about 500 years ago this year. They basically caused a mass disposition of Sephardic Jews, so Spanish Jews, who moved to Portugal and then to the new world.

We’re able to establish that there was a much larger diaspora that was of conversos, people that converted to Catholicism to survive than had been anticipated. That mutation and this founder mutation that we found in the indigenous population were the two most common mutations in the whole cohort. So, that was really illuminating and it helped me understand the impact of world history, and not surprisingly we saw a bunch of Spanish mutations too. There are other mutations that are common in Spaniards that are seen in this population.

One last population this represented, and again bringing together our world history view is, there was an African founder, and that reflects the impact of the slave trade. Especially in Central America and in Mexico on the gulf coast, because remember that was where a lot of the slave trade entered. We saw exactly what you’d expect for the admixture, the type of blend of cultures and ancestries that you see in Mexico. Again, I learned a lot about ancestry, anthropology, and epidemiology by trying to do the right thing. That is, take care of people who have no access to care.

Chris Riback: I was just going to say, you’re raising one of the most fascinating parts of these conversations for me is the intersections. So often the intersections I come across are from oncologists who are studying or have worked in one type of cancer and from working in one type of cancer, lung cancer, stomach cancer, and other areas they take those findings and apply them in other areas of study and that mix has not stopped fascinating me.

What I’m hearing from you is, you’re not a historian by study, and you’re not an anthropologist by study, but is the fact that you are an oncologist and a geneticist, was that mix of your background part of what enabled you to really go forward on the type of investigation that you did there?

Dr. Jeffrey Weitzel: Yes, absolutely. I think that geneticists follow lineages and sometimes those lineages go way back. That’s a natural interest on that side. The oncology side of me is all about, what’s the problem? What do we need to help with? Where are we having a problem that we need to take care of people?

So, you’re right. I’m sort of a junior anthropologist as a result of this. Really, I’ve read the books. I’m starting to read the books and the things that relate to these historical angles and then it actually provokes new scientific questions. You look at these ancestries but what was important at the time, let me just add one other thing, is remember we were talking about disparities in the access to care and the absolute limitation because of the economics.

The other thing we tried to do is we said, okay 75 percent of the patients who have a mutation have one of them that we’ve determined were on our shortlist. They were recurrent. They’re historical, ancestral. We already knew these genes didn’t mutate frequently, meaning new mutations aren’t quite found that open. We said, can we do a cheaper test.

I actually turned around and created in my laboratory, I like to call it the pragmatic research, which is can I get testing done cheaper for my patients without having to spend $4,000 a test? And we did. We created then a platform that uses mass-spectroscopy, a $20 test that picked off 75 percent of the true mutations. That allowed me, even in my county hospital population in the US, before Medicaid started paying, we were able to figure out the 10 or 15 percent who are carriers based on this very cheap test. Turned around and converted it with a commercial test at a cheap cost to now have a tool for the whole family.

We were leveraging science to be pragmatic and literally translate directly into access to care based on knowledge of epidemiology. What’s happened since then is that we started to raise that flag and really push that theme, that don’t leave anybody out, any population that looks like it has hereditary breast cancer probably does. How do you take care of these people? We need people who are trained in genetics and oncology, so we married this to what I will call our, we have an award-winning doctor training program. So doctor, nurse, and genetic counselor training program.

Chris Riback: Is this the cancer genomics education program with Dr. Blazer?

Dr. Jeffrey Weitzel: You’ve got it. Dr. Blazer.

Chris Riback: So please go ahead.

Dr. Jeffrey Weitzel: So Dr. Kathy Blazer was a genetic counselor. She was one of the first genetic counselors that I hired when I got my first education grant back in 1997. She was obviously quite young when I hired her. She’s Dr. Blazer because along the way we had gotten really involved in, really brought our education program because we realized post-medical school training, and even fellowship training of oncologists was completely deficient in understanding how to apply genomics and cancer.

That’s become even more so the case. I’m sure you’ve had other podcasts where you’ve talked about precision medicine, so this whole intersection of genomics and oncology is just so stimulating and so fascinating. People need that training that they didn’t get. Not only that, but she championed what we call situated learning. We’ve taken practitioners who are in practice and use their own cases to help them learn and it turns out that it’s the most profoundly effective way to train practitioners is to make it situated, it’s relevant to their practice today, and use their own cases in that learning.

Suffice it to say we developed a program that’s over 100 continuing medical education hours and involves a lot of immersed learning. She’s Dr. Blazer because she went and got her educational doctorate at UCLA, while she continued to work at City of Hope and has raised the bar even further on our program. I’m very honored that last year the American Society of Human Genetics recognized us as a team to award their education award.

Suffice it to say, we’ve taken this award-winning program and said, okay, how can we increase access to care, and how can we leverage this epidemiology. Because even though we continue to expand access to this care in the US. I will say there are still deficits in the underrepresented minority populations, and disparities there. Also, among Hispanics in the US. We have made a lot of progress there. We now have trainees in every state of the union and 26 countries.

How do we then take what we learned and maybe take it to Mexico? This is where, really BCRF, has been so instrumental. These things take a while to develop. We have to be patient. Even though we’ve been doing testing for 20 years in the US they still don’t have a fundamental access to genetic cancer risk assessment in Mexico, Central America, and most of South America. This can be said also for, probably, Africa and a few other places.

We said, hey we’re training people, but it doesn’t do them any good to get trained if they don’t have tools. So, I have a registry protocol, that allows return of results that are clinically actionable to the patients and the clinicians who are participating in this research. So, what we’ve done is created an implementation intervention so, there’s a whole science of dissemination and implementation, I’ve had to learn multiple sciences beyond oncology and genetics to do research.

Behavioral research, will they show up? What are the social-cognitive aspects of Latinas preparing to undergo risk-assessment. I’ve learned so much from my colleagues and embraced my colleagues who are multi-disciplinary, it’s so important. Again, genetic counselors are so key to that process.

In any event, we, embracing all these various specialties and things, and learning how to do dissemination and implementation which is really, how do you take this practice that you feel is medically important and will help to save lives, how do you get other people to adopt it and what are the barriers?

It’s a whole study. They’re the PIs of their own registry but they send the biopsy specimens to my laboratory at City of Hope where Joseph Hertzog and Danielle Castillo both work in my lab and they’re just awesome. They do all this work.

They receive all the samples, we extract the DNA. Even though I didn’t want to be a service lab. I have no intention of being one of the major commercial genetic testing laboratories. I realized, if we did it cheaply using a number of different tools, what we can now do, BRCA testing plus another 30 genes all for under $100 per case. That puts it into the realm of research funding, and into the realm of plausibility for these other countries if they can pick up the technology.

It’s partly tech-transfer too. In the meantime we said, well you don’t want to just give them the tool and tell them to go, test people, you want them to take care of them appropriately. So, we trained them in the course. They get the high-level training in cancer genomics and how to apply it in the clinic and they go back to their own setting, they create their own clinic and we help coach them on creating clinics, which is part of what dissemination and implementation is about.

By putting them in our registry we accomplish two things. We now, continue to grow the body of knowledge about epidemiology. So, what are the country-specific patterns that will help to convince their own health care administrators that it’s important. And second, they’re really giving that care to their patients and helping to find ways to take care of that risk when they find it.

I’ll give you an example that is so pragmatic. Unfortunately, most of these people still have cancer when they’re identified, we’re not quite at the identifying the at-risk relatives, but if a woman at 35 years old or 40 years old comes in with breast cancer, at whatever stage… I will tell you the stage distribution in countries without good screening is dismal. It’s like stage three. But, they have big families. And so, if we can identify the risk in that woman, she gets good care and survives, and we find out that because she is a BRCA carrier she has an extraordinary risk for ovarian cancer that could take her life. With almost no chance of early detection there.

That’s an intervention, remove her ovaries and tubes out after the completion of childbearing that could save her life. Then, on top of that, we now have the anchor for that family, we do what’s called cascade testing. Now we can go to her sisters. Even if we can’t provide comprehensive care for everybody in that family, at least half of the individuals won’t carry the mutation so we can give them reassurance that they’re average risk. The other half we can focus what limited resources we have.

This is about allocation of limited resources in low and middle-income countries. If I looked at it, at a population level, how do we help in a bigger way? Our goals are nothing short of changing entire counties’ plans for the care of high risk individuals at risk for breast and ovarian cancer. At the immediate level, I believe we are saving lives now by not waiting until genetic testing is somehow implemented by commercial firms at an adequately low price that the countries with such limited resources are willing to pick them up and integrate them.

We’re really creating the infrastructure to implement these cares and getting immense experience for the people locally and for our general knowledge of epidemiology to help guide these directions. Again, the BCRF funds have been so important to be able to have the patients. We literally develop these programs one city at a time. We’re in Mexico City, Guadalajara, Monterrey. We just opened up a clinic in Tuxtla which is in Chiapas.

Even in a poor country or a low and middle-income country, this is like the poorest.

Chris Riback: And historically there’s been real danger there.

Dr. Jeffrey Weitzel: That’s right. Real danger, and historically disparities even within that setting. The more indigenous people, and there’s a lot of disparities. We’re partnered there with Francisco Gutierrez and his clinics. He trained with us. We went and did a site visit back in January before COVID-19. He was a most gracious host but we got to see where they’re going to do their work, we got them logistical support and we’ve already tested over 50 patients for his clinic.

That will serve people in Chiapas all the way down to Guatemala and into Oaxaca, so a very large area that they’ll help to serve. We’re also in Bogota, Columbia, Medellín, Columbia, and Lima, Peru. This is the nucleus of the network. I will tell you that overall supported by Breast Cancer Research Foundation. We’ve helped to test more than 4,000 women over the last five or six years. That means 4,000 families with access to care. At least 15 percent are carriers of a significant mutation that influences their care.

We’re starting to create a legacy in terms of publications as well. We have one publication from 2014 on triple-negative breast cancer, and out of 190 women with triple-negative breast cancer we found that 27 percent had a mutation on our quick screen. We screened 190 women in two weeks for $5,000 and came up with 45 carriers that quickly.

You just can’t do it on a scale when we’re being nimble, we’re doing what we can. We found out just recently, we got some really exciting data coming out that we’re writing right now, so it’s unpublished suggesting that there may be a difference between the mutations. That the mutation that’s that founder mutation while it confers great risk, also may confer some survivor benefit if given chemotherapies. We’re actually starting to get into the patho-biology of breast cancer, not just who’s at risk but what are the outcomes? We’re also studying what’s the uptake of risk reduction surgery.

Do the women who we identify get access to the care? Remember this is all on the backs of those saints, those clinicians, at each of these sites. We said, we’ll help you define the risk, but you’ve got to figure out how to take care of those patients. Rather than saying it all had to be lined up before we started we said, let’s get this going and the natural experiment, which has been just amazing, is that when given the opportunity, we give the patient the information, let them be empowered. Give the doctors the information, let them be empowered. They find ways to work the system and get the care.

This has been really remarkable that they’re going to figure out how to provide the care where they are and it’s respect for cultural and situational circumstance. We aren’t promoting US guidelines, we’re promoting locally relevant guidelines in terms of the care that they provide.

I’m becoming more adept and understanding of all of these very important, I’ll call them, cultural humility is I think the new word. Understanding how…

Chris Riback: Yes, it’s a terrific phrase. In listening to you so many key ideas and such important concepts jump to me. When you say you’ve tested 4,000 folks. It goes beyond that. The cascade effect of what you’re learning is all of a sudden, the folks within that testing environment who do discover that they have a genetic mutation, I know you already know this, you’ve just now positively affected at least with arming them with information about themselves, their whole families. Every member, sisters, granddaughters, nieces. The list goes on.

Dr. Jeffrey Weitzel: Absolutely.

Chris Riback: That’s number one. Number two the thing that occurs to me, so tragic, I’m certain you feel the same way. You mention that so often in some of these locations in the US, in other places where there is disparity of care and disparity of access that the person who comes in, comes in because the risk identifier that has come up in her life is the actual cancer. You described it as so often they come in and it’s stage-three cancer, they haven’t been identified before that. Obviously that’s tragic and sad and you wish to goodness that somehow you’d been able to identify them earlier.

That said, same thing, then they go through the process and all of a sudden you’re now able to arm the rest of their families, yes maybe, you phrased it, maybe you’ll be able to find some other type of cancer that they might have been, might have come across, or had ultimately. By doing this care you will have identified that. You mentioned ovarian cancer as an example.

Lastly, and this is kind of my question, one question is, please correct me if I’m not interpreting the lessons that you’ve been describing because I’m just trying to communicate back to you what I’m hearing in getting to hear the work and the study and impact that you’ve made. Going into this conversation, one of my main questions was, okay Doc you’re worried about disparities, where do you begin. Is that a money question? Is that an access question? Is it a social question? Is it a health care professional question? Is it an education question? Is it a science question? When you talk about disparity what exactly does that mean, and what I’m hearing from you is, yes. It means all of that and that probably, is what defines one of your current research programs, the multi-modal approach to address these disparities. It really is multi-modal isn’t it?

Dr. Jeffrey Weitzel: Absolutely. It’s creating infrastructure, generating knowledge, being able to help influence health policy decisions, so a truly global profile. Right?

Chris Riback: Yes, yes, it’s a public policy.

Dr. Jeffrey Weitzel: It’s a public policy. Again, by demonstrating the impact. By going and not waiting for little pieces to come together, but to put it all together and allow my colleagues to take the lead. They really do take the lead. They’re extraordinary in their efforts. We’re publishing locally. We’re publishing globally. The idea is that they will establish that the problem exists and that there’s a pathway to some solutions.

We’re laying the groundwork. One of our colleagues we were working with Alejandro Moja, he was the former director of the National Cancer Institute in Mexico City, and he was at one point or another also working as an agent of the Ministry of Health. One of his charges was to create a national cancer plan. We were able to at least, get his ear because he was one of our earliest collaborators, probably our biggest critic, but once convinced [he was] our staunchest ally.

I appreciate my friendship and my collegial relationship with him to date, but he had written in, to this national cancer plan, allowed us and my partners in Mexico, to help write a component of the plan that started to integrate the concept of genetic risk assessment and the need for scale-up. To be able to take the lessons that we’re learning from the BCRF project, expand them, and now apply them to other parts of the country beyond the major population centers.

I think we’re already seeing the path we need to take. It’s also sobering, I’ll tell you. We went there in January, had a physician round table and all the same things were still there. What’s even worse was at the time, because of political changes, and we know that well in the US as well, that things change. Support for different programs change. They were in the process dismantling their safety net program called Seguro Popular which threatens our program so we actually talked about starting a social movement.

I’ve got to tell you it’s so inspiring to see them standing staunchly to support their patients and those families and realizing that they’ve got tools that can make a difference and finding a way. Just finding a way. As they say, nature will find a way. Humankind will find a way. If you are respectful and understand that.

Chris Riback: If humankind will find a way, and you may have just answered the question that was going through my mind, which is, listening to you, it is beyond obvious that you are inspired. It’s beyond obvious that you are enthusiastic. Are you optimistic?

Dr. Jeffrey Weitzel: I am passionate and I believe, yes, you can’t do this kind of work without being an optimist. If I had been a fatalist we never would have started. We would have said there’s too many barriers. In fact, we did some focus groups and things and things. There was a fairly, concern about, there’s so many elements working against the integration of this care but we put a wedge in there.

You put the wedge in, which is knowledge, the teaching, the training, and then you let them be inspired and find a way. Again, we just started building tool and putting them together and hence the multi-modal intervention. The recognition that it’s the registry because I have to do the testing in my lab now. Eventually that’s not going to be the case, it’ll be available commercially but cheaply and good quality. They’ll already have in place the structures for the follow-up care. Again, it’s not just getting the risk assessment done it’s what do you do with them once you know they have risk. It’s so inspiring to just follow my colleagues.

I give them the tools they’re the ones who are really doing the hard work. It’s easy enough for me, well it’s not easy to write grants. We write grants, we sit back, it’s not an ivory tower. I get out into the field. I do travel. We do site visits at these sites because we want to see what they’re up against. We want to see what they’ve done. We come in, not like an audit. It’s a friendly audit. Here’s what you’ve done. Boy, these other sites in Peru they got over this barrier by adopting this. So, we help them adopt those practices and share it among this group and we have a cohesive group of people who recognize common goal. They’re in multiple different countries and we’re innovating together.

We publish together. We innovate together. I try to never stop learning and listening. I tend to talk too much. I get that all the time. But I do listen. My absolutely spectacular colleagues in Mexico, Dr. Yanin Chavarri Guerra in Mexico City Dr. Cynthia Villarreal Garza in Monterrey, they’re some of my longest-standing colleagues and partners and I think they are brilliant. They are the future of oncology and prevention in Mexico––absolutely so. Julio Abogadas who’s in Peru at the National Cancer Institute in Peru, a breast surgeon. Again, the future of prevention there along with Pamela Amorra.

That’s where I get my inspiration and I think it helps me understand our impact well beyond the walls of the City of Hope. I mentioned also, here’s something interesting. We’re trying to help them through strategic allocation of limited resources. So at the end of the day if you’re just a healthcare policy wonk, we have a limited amount of money and so many needs, how do you do this? I would tell you that there’s a big drumbeat for can we get breast cancer screening for all women?

I don’t want to offend anybody, but for many women they might be a 1 in 10 chance at most, maybe less, we’re being able to stratify that more, but the BRCA carrier’s an 8 out of 10. If I have only a certain amount of money to apply for screening and people are not getting regular screening, only 19 percent of women are getting breast cancer screening in Mexico despite the fact that it’s technically a covered benefit. As a basic limitation there, if I could only screen one set of people. It’s when Willy Sutton was asked, why do you rob banks in the 1940s.

Chris Riback: I know why. That’s where the money is.

Dr. Jeffrey Weitzel: That’s where the money is. Okay. The same applies here. If you apply the strategic allocation of limited resources. If you can cheaply identify those at highest risk you’ll make the biggest impact with the least amount of money quickest there. I’m certain when I look at the uptick of the risk reduction removal of the tubes and ovaries, and the other side, mastectomies that are being done as prevention for some of these BRCA carriers with breast cancer, I’m confident that we’ve already prevented a bunch of ovarian cancers and probably quite a number of breast cancers.

This is prevention in the moment while we’re still working on the implementation, and that’s exciting. Think about this, is that they’re teaching us how to get limited resources to work for a population, we can take that home and start to address disparities in the US and in low resource settings. It’s reverse-engineering. It isn’t that it’s just a one-way street where we’re just bringing stuff to them. We’re learning from them and I hope to bring that to disparities in the US.

Chris Riback: I am certain that you are. I knew coming into this conversation that you are recognized as a world-class oncologist and geneticist what I didn’t know and what I’ve learned is you’ve got a bunch of other titles, historian, anthropologist, sociologist and I would dare say a potential for a novelist because not only do you tell a great story but there’s a remarkable story that you’ve uncovered. There’s something multi-cultural and extraordinary there. Thank you. Thank you for the work that you do and thank you for taking the time to tell me about it.

Dr. Jeffrey Weitzel: Well, thank you for your interest. I’m so pleased that you would take an interest and willing to help to share this. I’m always in great debt to the Breast Cancer Research Foundation. I’ve been a long-standing scholar with them. I’m so grateful that they’ve had the patience and understand the mission. They’re one of the few organizations in the world that’s truly global. They have global impact. I just can’t say enough positive about that and how important their funding is.

I think they are the largest public or private funders of breast cancer research in the world and I truly see a global understanding on their part. Everything from absolute basic biology to what I would call pragmatic translation. I’m probably from the middle of that curve on over to pragmatic translation. Really honored to be one of their scholars, so I can’t say enough for my gratitude for their support.

Chris Riback: That’s wonderful. Thank you.

Most breast cancers are not the result of inherited mutation in cancer causing genes. For families with a high incidence of breast cancer, however, a genetic component may underlie an inherited risk. We know the BRCA genes are the most common of these inherited mutations, but scientists have uncovered many more genes implicated in a risk of breast cancer.

How can researchers provide more precise risk estimates so that individuals with inherited risks can make informed decisions about their health, so that the right women are getting the right tests at the right age?

Dr. Robson is conducting studies that employ advanced technologies that incorporate information from genetic tests to enhance the precision of genetic risk assessment in women with mutations in the BRCA gene.

Dr. Robson has been a BCRF investigator since 2006 and is an associate attending physician of Clinical Genetics and Breast Medicine Service in the Department of Medicine at Memorial Sloan Kettering Cancer Center.

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Read the transcript below:

Intro: Most breast cancers are not the result of inherited mutation in cancer causing genes. For families with a high incidence of breast cancer, however, a genetic component may underlie an inherited risk. We know the BRCA genes are the most common of these inherited mutations, but scientists have uncovered many more genes implicated in a risk of breast cancer.

So how do genes influence breast cancer risk? And can we develop strategies to precisely predict risk on an individual level? In other words, how can researchers provide more precise risk estimates so that individuals with inherited risks can make informed decisions about their health, determining the level of risk for enhanced screening so that the right women are getting the risk tests at the right age?

Dr. Mark Robson is one to ask. With Dr. Kenneth Offit, Dr. Robson – among other activities – is conducting studies that employ advanced technologies that incorporate information from genetic tests to enhance the precision of genetic risk assessment in women with mutations in the BRCA gene.

Why does he do it? What motivates him? You’ll want to hear Dr. Robson’s thoughtful response about the breast cancer community that included references to James Madison, Virgil, and the that that, as Dr. Robson says: “Life is full of nuances,” and that “everyone experiences” the disease “in a different way.”

Some background: Dr. Robson is an Associate Attending Physician of the Clinical Genetics and Breast Medicine Service in the Department of Medicine at Memorial Sloan Kettering Cancer Center. He is currently the Clinic Director of the Clinical Genetics Service and the chair of the Cancer Genetics Subcommittee of the American Society of Clinical Oncology. He has been a BCRF Investigator since 2006.

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

Dr. Mark Robson: Thank you for having me. Glad to be here.

Chris Riback: I’d like to start with your helping differentiate between two paths to breast cancer, those that result from inherited mutation and cancer causing genes and those that don’t. Do the types of breast cancers that result from these paths differ and which path is more common?

Dr. Mark Robson: Yes. So, the vast majority of breast cancer is not due to mutations or the term now is pathogenic variants, which is a little bit more fancy but precise. The vast majority of breast cancer is not caused by those genetic changes. They arise because of alterations that occur in the DNA and it’s just acquired through life. But there are a fraction of women who develop breast cancer because of a specific inherited mutation.

And they’re in general have the same outcomes as women who don’t have mutations. And with one exception, the breast cancer is generally seem to resemble those of women who don’t have mutations. The one exception is for women who have mutations in BRCA 1, which is linked to an increased risk of a triple negative breast cancer, which is a particular subtype.

The reasons for looking for these mutations are that … There’s a couple of different ones. One is that women who have mutations, for instance in BRCA 1 or BRCA 2 may be an increased risk for other types of cancer, either second breast cancers in the other breast or ovarian cancer. And that risk means that we should do different things to follow them up.

Also, their family members may be at increased risk if they share the mutation and benefit from specific surveillance approaches and potentially even preventive surgeries. And lastly, women who have metastatic breast cancer with mutations in some genes, although not all genes may benefit from treatment with a specific class of drugs called PARP inhibitors.

Chris Riback: And that’s what I just wanted to ask you about. When we talk about inherited risk or pathogenic variants perhaps and genes and breast cancer, most often we hear about what you just raised, BRCA 1 and 2. But those aren’t the only genes implicated in a risk of breast cancer, are they?

Dr. Mark Robson: No. Indeed not. When a new type of technology called next generation sequencing became available a number of years ago, it became possible to test individuals for many different genes at the same time. And once that became possible, so-called panel testing came into the clinic.

And we discovered that a significant number of women have pathogenic variants or mutations in genes other than BRCA 1 and BRCA 2. And while BRCA 1 and BRCA 2 are still the most common identified inherited risk factors, there are a range of others that in aggregate are equally calm.

Chris Riback: There was a quote I saw recently from Larry Norton of Memorial Sloan Kettering, but also obviously BCRF, where he said, “We know from our data at Memorial Sloan Kettering that if you only test people with strong family histories, you miss half the cases.” And I know this is a key question. If we know inherited risk is a thing but we don’t necessarily know which genes drive the risk, how can individuals with inherited risks make informed decisions about their health?

Dr. Mark Robson: Well, I think that that’s a topic that we’re having a lot of discussions about right now. So, I think what Larry was referring to was that even among women who have BRCA 1 and BRCA 2 mutations… Sorry about the phone. Even among women who have BRCA 1 and BRCA 2 mutations, half of the women with mutations aren’t found until they themselves develop a cancer and would not have been tested based upon what their family history is until they themselves develop a cancer.

That’s one component of the unidentified risk. The other component is that the genes other than BRCA 1 and BRCA 2 are actually much less strongly predisposing than BRCA 1 and BRCA 2. So, they may move through families without actually causing cancer. And so, can be hidden, if you will, until perhaps someone is unlucky enough to develop the disease and get tested.

Chris Riback: Let’s talk about your work and some of your goals. Because among your goals, as I understand it, is to determine not only how we can make more precise risk estimates but how we can precisely predict risk on an individual level. Take me through that process. How are you trying to do that? And perhaps relatedly, what are single-nucleotide polymorphisms?

Dr. Mark Robson: Right. Should we call SNPs because there’s so much easier to say?

Chris Riback: Thank you. We will call them SNPs.

Dr. Mark Robson: Yes. SNPs. So, what we’ve been talking about so far are so-called rare variants. In other words, everybody has the BRCA 1 or BRCA 2 gene but very… Because they perform normal functions in our bodies. But very, very few people actually have mutations or pathogenic variants in those genes. In the general population, it’s probably only around one in 400, maybe one in 500 people have a mutation. Although in certain populations that we’ll talk about later, it may be more common.

These rare variants are predisposed to cancer but not everybody who has a mutation in one of these genes gets cancer. So, for instance, for BRCA 1, it’s probably about 65 to 75% of women get breast cancer and 40 to 60% get ovarian cancer depending on the study. For BRCA 2, the numbers are perhaps a little bit lower. It’s maybe two thirds get cancer and 15% or so get ovarian cancer.

And for genes like those other so-called moderate penetrance genes, those other genes that we talked about a little bit earlier, one such gene is called CHEK2. And for those women, the lifetime risk of breast cancer is maybe about 25%. So, the question becomes what’s different about the women who do get breast cancer and don’t get breast cancer when they have a mutation in one of those genes? And there’s a number of things that play into that.

But one thing is genetic background. And we have millions and millions of places throughout our DNA where we’re subtly different from other people. These are so called common variants or SNPs. And it turns out that some of those SNPs are associated with greater or lesser risks of disease. And this isn’t just breast cancer, this is all kinds of diseases, diabetes, cardiovascular disease, et cetera, et cetera.

And they’re not mutations in the sense that they don’t cause problems with genes but they’re just part of us, part of our background. And we can now through genetic testing in research settings, identify the pattern of common variation that a person has. And what we found is that certain patterns of common variation, so-called polygenic risk scores are associated with greater or lesser risks of disease both in the general population and in people who have mutations in genes like BRCA 1, BRCA 2 or CHEK2.

So, one of the things that we’re trying to do is measure this background variation in individuals, predict how that might affect the risk that’s associated with say a mutation in BRCA 1 or BRCA 2 and see whether if we give that information to women, the differences are sufficient to influence their decision making about things like preventative surgery.

Chris Riback: Almost focusing the light on the amount of risk based much more on an individual reading it seems than on the readings that we have had to date.

Dr. Mark Robson: Correct. Because right now when a woman goes in for a genetic counseling, for a BRCA mutation, she is often given a fairly wide range of potential risks. Say, “Your risk may be anywhere from 65 to 95%.” And what we’re exploring is whether it is helpful to those individuals to become a little bit more precise. There’s still going to be some range but the question is can we narrow that range in a way that it’s helpful?

And it may be that for the very strongly predisposing genes, the precision may be helpful. We may narrow the range but the range may still be so high that it doesn’t change decision making. But for this other group of genes that we have been talking about, the moderate penetrance genes, it may matter.

Because if your average risk is 25 to 30% but there’s some group of women that are in the 15% range and some group of women that are in the 40% range, that may well have an influence on what they decide to do. So, we’re also as a next step looking at polygenic modification of moderate penetrance.

Chris Riback: And is this the Prospective Registry Of Multiplex Testing, PROMPT? So, we had SNP earlier and now we have PROMPT. First, is this the group that you are doing this work with? And then two, how would you characterize where you are on the work? How far along would you say you are?

Dr. Mark Robson: So, PROMPT is actually a little different. PROMPT is when multigene panel testing became available, it is the thing about which we have very little evidence to understand how people are receiving the information, how the information is being communicated to them and what they are choosing to do with the information.

This was something that multigene panel testing was rolled out commercially, not as a research test, with very broad adoption very quickly but with still a lot of questions about how best to use the information. So, we created PROMPT as a voluntary internet based registry for people who had been found to have mutations on multigene panel testing to share their experiences, to tell us what they had because that in and of itself was something that was interesting. What were the diseases that they had, et cetera.

But also, what were they doing subsequently in terms of screening or surgery? And what was their understanding of these alterations? What had they been told? What had they received? And now, we’re following these… Largely women, not exclusively but largely women serially over time to try to understand longitudinally what they’re doing.

So, that’s an observational project that I think is very important because it’s giving us a view of what’s happening in the real world with multigene panel testing. With regard to the risk modifier work, we were facing some challenges getting a clear based… Which is a laboratory approved assay done that we could share with people that we had enough confidence would be accurate.

We’ve now circumvented that hurdle through a relationship with a vendor, have achieved the appropriate regulatory approvals and are now moving it into the clinic to start offering the testing to women who have had newly identified BRCA mutations so that we can give them this information and essentially measure what it is that they choose to do with it.

Chris Riback: And the point that you were just making, I’m sure it’s a question that any person would have first of all around genetic testing and understanding one’s own risk and modifying one’s own risk as much as possible. But in particular, individuals at risk of carrying BRCA 1 or 2 mutation, this becomes even more powerful for them.

You wrote in a recent editorial in the journal of the American Medical Association with a colleague, you wrote a little bit about this. And one of your lines was, “Identification of individuals at risk of carrying a BRCA 1 or 2 mutation can be lifesaving and should be a part of routine medical care.”

Now, that may have been geared towards a particular population but I thought that might be something to get some guidance on or some insight on from you because it’s an area obviously that so many people would be curious about.

Dr. Mark Robson: Right. So, we have reasonably strong observational evidence. That if you identify a woman who’s having a BRCA mutation and then prevent her from getting ovarian cancer by doing a preventive surgery to remove her fallopian tubes and ovaries, that that will improve the survival of the population because screening for ovarian cancer is inadequate and it’s a tough disease that frequently presents an advanced stage.

There is also some potential benefit from women who choose to undergo preventive mastectomy, although whether that has much of a survival advantage is not clear. But prophylactic oophorectomy is something that we believe does save lives. So, finding women who have BRCA mutations, that’s not something that you want to do lightly, certainly not in younger women because premature menopause is quite a significant impairment to quality of life and potentially to longterm health.

Dr. Mark Robson: So, finding the women who’ve got mutations is important. The way that we have done that to this point has been by using things like family history to try to predict who is more likely to have a mutation. Remember as I said earlier, it’s only about one in 400 to one in 500 in the general population. So, creating a system of testing, everybody becomes challenging.

The thought is perhaps to start this process by concentrating on groups who have higher risks of carrying a mutation. So, for instance, the population of the Ashkenazi Jewish individuals. So, individuals of Eastern or Central European Jewish descent have about a one in 40 chance of carrying one of three specific BRCA 1 or BRCA 2 mutations.

So, nearly 10 times higher. And there has been thought now that perhaps everyone who is of Ashkenazi Jewish descent… And defining that becomes a little bit of an issue. But everybody who’s of Ashkenazi Jewish descent should at least be offered or have a discussion about the possibility of undergoing BRCA testing, at least for those three common mutations.

Chris Riback: So, it’s a bit of a shifting of the thinking around who might want to do it. And I’m sure that there’s still much discussion and increasing the number of the amount of testing carries… “controversy” is the wrong word, but one wants to manage – and you were saying this – and handle testing appropriately.

As I’m talking to you, so much of it seems what you think about, what you have worked on in your career, what you’ve dedicated yourself to is around the genetic component and about the considering and the managing of risk. I found myself thinking about you almost as a medical actuary doing, thinking… So, why? What interests you about that? And have you ever thought of yourself as a bit of a medical actuary?

Dr. Mark Robson: No. I never thought of myself as a medical actuary. Because why am I interested in it? That’s a fascinating question that I’ve really never deeply thought about. My perception is that life is full of nuance. And what I enjoy about this area is trying to communicate with people about uncertainty and help them navigate that in a way that is concordant with their values and how they want to approach managing potential threats to their health.

I mean, not everybody who has a BRCA mutation gets cancer. And certainly, not everybody with a moderate penetrance mutation gets cancer. And yet when they have a test result, many people seem to internalize that as a diagnosis, essentially pre-cancer. And the question is how can we help them navigate that and just recognize that this is something that is a risk that you know about. Perhaps there are others that you don’t. And that’s what I enjoy about it.

Chris Riback: And does that lead in some way to your clinical work? I mean, it wasn’t lost on me that my understanding of the clinical side for you, you’ll correct me if I have this wrong, is that your practices weighted toward the management of young women with breast cancer, especially hereditary breast cancer. I recently had a discussion with Doctor Ann Partridge, who runs the young and strong program for young women with breast cancer. The disease is different for young women, isn’t it?

Dr. Mark Robson: I think that the disease is different for everybody, right?

Chris Riback: Yes.

Dr. Mark Robson: I mean, everybody experiences it in a different way and it has a different impact. I do work a lot with younger women just because I work a lot with inherited risk and that overlaps. But also take care of people who are older as well. And it’s the same concept. I mean, if you think about after a diagnosis and treatment of breast cancer, once again, people are living with a pretty fair degree of uncertainty.

About at least for a while, “Is this going to come back? How am I going to integrate this into my life? ” And again, it becomes a conversation about moving forward in the face of uncertainty. And uncertainty with a possibility of something not good happening, right? And I think that from the humanist perspective of Madison that being a little bit of a Virgil in that setting, is a privilege. And I enjoy doing that.

Chris Riback: Was it always medicine for you? Was science always the direction that you were going to go? You mentioned Virgil. Were there other areas of interest for you growing up?

Dr. Mark Robson: I’ve always been interested in the arts and humanities. But mainly as a way of, again, informing perspectives on life. Gosh, I’m getting all philosophical here on a Thursday afternoon. But no. I mean, I’ve been joking with my daughter who’s now in 10th grade and I remember actually starting thinking about doing medicine when I was in 10th grade biology class.

So, yes. I mean, it pretty much has always been medicine for me but for different reasons. When I was younger, it was because it was tough and it was hard and I felt like it was intellectually challenging, which has a certain arrogance to it. And then, as I got older, it became much more because it was a life of connection. And connection not only to your patients but connection to your colleagues and connection to the broader world. And I think that’s a very nourishing thing.

Chris Riback: Yes. It’s not a bad way to go through. And to close out, I’d be remiss if I didn’t ask you, doing the amounts of research that you do and that other researchers, scientists, doctors do can be challenging at times, what role has BCRF played in your research?

Dr. Mark Robson: Well, BCRF has been an incredible financial supporter. The model is very unique. And the idea that you have funding to explore ideas that would be difficult to get funded through other mechanisms because of the novelty, because of the newness of what you’re trying to do. So, there’s that component to it.

The other component goes back to what we were just talking about is that it’s a phenomenal community of both researchers but also… And perhaps more importantly, patients, family members, supporters, who are energizing through their dedication to the course and their energy for the course.

And so, I think we all talk about the research support that’s critically important. But the community writ large is in my mind equally important and perhaps even more so.

Chris Riback: Well, thank you. I’m certain that they’re grateful to have you part of that community. And yes, it’s a remarkable community to say the least. Dr Robson, thank you for taking the time. And of course, thank you for the work that you do.

Dr. Mark Robson: Thanks very much. Appreciate it.

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 and has been a BCRF investigator since 2001. 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.

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Read the transcript of the conversation below: 

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 “a-ha” 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 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 “a-ha”? You talked to earlier as well about potential a-ha moments. Was that an a-ha 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 layperson 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 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.

To learn more about breast cancer research or to subscribe to our podcast go to BCRFCure.org/podcasts.