Clear Search

Lowering Barriers to Genetic Testing with Dr. Susan Domchek

By BCRF | June 28, 2023

Dr. Domchek talks about her “virtuous impatience” to bring genetic testing to all who need it and to use it to inform treatment after a diagnosis

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.

Read the transcript below: 

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.