What’s Your Family History? with Susan M. Domchek, MD

 Even though you cannot change your genetic makeup, knowing your family health history can help you reduce your risk of developing any kind of health concerns. Today, we’ll learn about how to better understand your risk of breast cancer, how to talk with your doctor and how to make better informed choices.  We’re going to help empower you to take an active role in decision-making about your health.

About Dr. Domchek

Susan M. Domchek, MD is the Basser Professor in Oncology at the Perelman School of Medicine of the University of Pennsylvania. She serves as Executive Director of the Basser Center for BRCA at the Abramson Cancer Center and Director of the Mariann and Robert MacDonald Cancer Risk Evaluation Center. Her work focuses on the genetic evaluation and medical management of individuals with inherited risk factors for cancer. Dr. Domchek is particularly interested in developing new cancer therapies, such as PARP inhibitors, for breast cancer patients due to genetic risk factors. An elected member of the National Academy of Medicine, American Association of Physicians, and American Society of Clinical Investigation, Dr. Domchek is also a member of the American Society of Clinical Oncology for which she had served on a number of committees. A significant contributor to the oncology literature, she has authored/co-authored more than 250 articles appearing in scholarly journals including the New England Journal of Medicine, the Journal of the American Medical Association and the Journal of Clinical Oncology. Dr. Domchek also serves on a number of editorial review boards, as well as on the Scientific Advisory Board for the Breast Cancer Research Foundation.


Adam: [00:02] Even though you cannot change your genetic makeup, knowing your family health history can help you reduce your risk of developing any kind of health concerns. Today we’ll learn about how to better understand your risk of breast cancer. How to talk with your doctor, and how to make better-informed choices. We’re going to help empower you to take an active role in decision making about your health. To help us learn how to better understand our family health history, which helps us better understand our health risks, let me introduce Dr. Susan M. Domchek. Dr. Domchek is the Director of The Basser Center for BRCA at the University of Pennsylvania. Dr. Domchek, it is an honor and privilege to have you on the show today.

Dr. Domchek: [00:42] Really excited to be here.

Adam: [00:43] Yeah, well is there anything else you want to add in from my short version of your bio?

Dr. Domchek: [00:47] Sure. Well, relevant to what we’re talking about today I am a medical oncologist. I was trained to take care of cancer patients, but at the same time, I was trained in genetics. Part of genetics is learning how a family history could impact your risk and how genetic testing can also give you further information about your risk for certain diseases, so that’s what we’re going to talk about today.

Adam: [01:09] All right, I’ll look forward to hearing about this. This is going to be great. Let’s just dive right on in, so first, give me a little background on your relationship with Susan G Komen and the research project you’re currently working on.

Dr. Domchek: [01:21] Well, since 2010 I’ve been funded by Susan G Komen as part of their Komen scholars program and this has been a terrific benefit for me in terms of research that I’ve been able to do with these resources. The specific project that I’ve been working on with Komen relates to a certain type of genetic testing that becomes very common in the past six or seven years and that’s something called multigene panel testing. And all that means is that when you go in with a family history or personal history of say breast and ovarian cancer, you might end up getting genetic testing and back just seven or eight years ago you would have been tested for maybe two specific genes. But nowadays because of the changes in technology and the fact that things have gotten really cheap, we can test you for like twenty-five genes at once.

Adam: [02:11] Wow.

Dr. Domchek: [02:11] But at the same time we really don’t understand what all of those changes really mean. So my project, which is called The Prompts or the prospective registry of multiplex testing is a large registry. It currently has more than sixty-five hundred participants throughout the country and they enroll on a website, give us information, give us follow up information and for a subset, we also do additional testing on their blood and in their tumor to better understand what these findings on the [Jag? 02:42] testing mean for themselves and for their family members.

Adam: [02:46] Wow, that’s fantastic. I love that. You’re really moving the ball forward in this new area. That’s fantastic.

Dr. Domchek: [02:52] What’s particularly interesting about genetic testing, and we’re going to get the family history in a minute, no matter what your genetic testing is family history always matters and is quite important, but genetic testing what we’ve really come to understand, and if you take as an example, genes called BRCA1 and BRCA2 and these are genes that are associated with the very high risk of breast and other cancers such as prostate cancer, male breast cancer, and pancreatic cancer. But if you know that you have a mutation in one of these genes it can help you understand what your risk of cancer is. It can help you make decisions about how to decrease the risk of cancer and even increasingly, which is very cool and important, is that it can mean that your doctor, your oncologist chooses particular drugs to treat your cancer because of that genetic testing results. So it’s become really, really important to have this information available.

Adam: [03:47] Wow, so I mean what I’m hearing you say is that to some degree they understand that based on your genetic makeup, certain drugs are going to be more effective for you than others, and I mean that’s kind of amazing.

Dr. Domchek: [03:59] Right, and this is one of the first drugs, drugs called PARP inhibitors. This was first approved at the end of 2014 for BRCA1 and two related ovarian cancer and since that time there have been a number of different PARP inhibitors approved for BRCA1 and two related ovarian cancer, breast cancer, and soon I’m sure that there’ll be approval for BRCA1 and two related pancreatic cancer. So the same drug, different tumors, but if the reason you develop that tumor is similar then these drugs can be effective in all these different circumstances, which is extremely cool scientifically and obviously a benefit for our patients.

Adam: [04:43] I love the fact that they said it’s extremely cool scientifically, that makes me excited about the work that you’re doing. That’s amazing.

Dr. Domchek: [04:50] I want to tell you why it’s cool.

Adam: [04:51] Yeah, yeah tell me, tell me.

Dr. Domchek: [04:51] So this is maybe a little far afield, but when we target things in cancer when we’re targeting drugs, it’s easy to figure out how to target something that’s turned on. You can imagine that, right? If something’s turned on, we’re pretty good at turning things off. It’s actually harder to figure out how to target something that’s turned off and these drugs, these PARP inhibitors were really the first drug to figure that out, and so it’s a combination of basic scientists of which I am not one. I know people in the lab figuring this out and then clinical trialists, which you know, that is somebody like me figuring out how to give it to people so it really takes really a scientific village to get these things from basic science understanding into improvement inpatient care.

Adam: [05:38] Wow. It’s a team effort. That’s fantastic. So let’s talk for just a minute also about family history. I don’t want to miss that. Can you walk me through just understanding family history and why that’s important?

Dr. Domchek: [05:50] No, it wasn’t that long ago that people really didn’t talk about their family history very much and cancer was sort of a word that people didn’t say and that was an incredible missed opportunity. So family history, knowing your family history helps in so many different ways. One is that in certain situations, family history can point you to a specific genetic susceptibility that you can get tested for and figure that out, so if you have a family history of colon and uterine cancer, that gives you a clue. Breast and ovarian cancer, that gives you a different clue so it’s really important to know the details of your family history so we know which genes were most suspicious for.

[06:29] But even in the event that you get genetic testing and your testing is negative, if there is a ton of breast cancer in your family, you are still at risk for developing breast cancer, even if there is no specific genetic susceptibility that’s been discovered because that’s another really important thing is that it’s not just genetics. The genetics has to be taken in consideration with your family history and it’s really, really important for people to know what their family history is and talk to their doctors. Some people don’t know their family history if they’re adopted or if they have very small families and that’s important for people to take into consideration as well.

Adam: [07:06] Right, and you mentioned that genetic testing that’s been discovered, I think is what you said there and I think the other point there is that just because you don’t have the markers that we’ve found so far doesn’t mean there won’t be others found later that someone might have, correct?

Dr. Domchek: [07:23] That’s exactly right. So that’s why if you have a very strong family history of cancer and so to say I’ve had breast cancer and many of my family members have, and I get genetic testing and that testing is negative. We actually have a phrase for that, we call it uninformative negative. Do you see what I mean by that?

Adam: [07:41] Yeah.

Dr. Domchek: [07:41] It’s like, okay, it was negative, but that didn’t help us any because it didn’t explain why that cancer runs in the family and that still happens quite a bit. We still have our work to do to figure out the missing heritability as we call it. What is it about those families that’s leading to cancer that we don’t yet understand?

Adam: [07:59] Wow, and are there any additional tools because I mean you also mentioned for people that have small families or may not know their families, are there any additional tools that are available that might help with that?

Dr. Domchek: [08:08] Sure, well the TDC has a tool that’s available online which just allows you to collect your family history in a way we call it a pedigree where we can kind of keep track of the relationship. You know-how is that cousin related to you through your aunt or through your uncle are on which side of the family and these things matter because when you come into your doctor or genetic counselor, we do look at these family relationships to try to determine what your risk. So that’s a really, really good way of keeping track of it and you know before Thanksgiving we like to sort of have this push to say, “Hey, while you’re meeting with your family over Thanksgiving, make sure you know if there’s any updates to the family history.” Today we’re focusing on cancer and based on Komen we are focusing obviously on breast cancer, but remember that your family history matters for all sorts of things, including things like heart disease and diabetes and other things like that.

Adam: [08:59] Right and if somebody is having that conversation they realize that breast cancer does exist in their family, what exactly does that mean regarding their own risk?

Dr. Domchek: [09:10] Right. Well, they’re the devil’s in the details and this is why genetic testing can be so helpful. There are a number of genes that if you have a mutation in one of those genes there is an increased risk of cancer, but it depends on the gene, how high that risk is. So BRCA1 and BRCA2 those lead to the highest risk for development of breast cancer, but there are other genes like mutations in [Check2? 09:34] and ATM where those risks are lower. And then finally if there’s no gene detected then we actually use a bunch of different models to get a sense of how high the risk is to the individual, and that will depend in part on how old people were when they developed their breast cancer. How many relatives had developed breast cancer, things like that?

[09:56] It’s also important to know that there are aspects of your personal history which increase your risk and those are things like if your breast tissue is dense on your mammogram. How much alcohol you drink? Whether or not you’ve taken hormone replacement therapy. How old you were when you had your children. So there are models that factor together all these different features including your family history to give us an estimate of breast cancer risk.

Adam: [10:22] Wow, that’s fantastic. Where would somebody go to see those models and be able to figure out what their own risk is?

Dr. Domchek: [10:29] So usually those models there is something called the breast cancer risk assessment tool, which is available to the National Cancer Institute and that has something called the Gail model. There are some limitations, these models, so it’s really best done in conjunction with your physician, healthcare provider, a genetic counselor that you can really understand what all this is.

Adam: [10:50] So then understanding your family history at the deepest level that you possibly can and then being able to take that and take those notes and those findings and share them with your healthcare provider to then really genuinely understand the holistic risk that you have. Is that correct?

Dr. Domchek:: [11:06] Exactly, exactly. On my mammogram did my breasts look very dense? Is it going to be hard for the mammogram to detect the cancer? And by the way, you having very dense breasts also is an independent risk factor of cancer. It’s a small risk factor relative to some others, but still, it adds in. There’s this constellation of factors and a holistic approach of your risk.

Adam: [11:29] Right, right. So last question, this has been an amazing conversation. I’ve learned a lot. I really appreciate it. My last question is if someone is at higher risk, what can they do right now?

Dr. Domchek: [11:42] So there’s a few different things. If you have a very elevated risk of cancer-based on a specific genetic susceptibility like BRCA1 or two, we definitely add breast MRI to mammogram in order to find cancers at an earlier stage. Women with BRCA1 and two mutations are also at increased risk for ovarian cancer so we actually do recommend that women have their ovaries removed by ages sort of forty approximately. There are also lifestyle factors so that everybody can do to reduce their risk of breast cancer and those include minimizing alcohol, having a healthy weight, getting regular exercise. And there’s been recent data that sort of a low-fat Mediterranean type diet with lots of fruits and vegetables and minimally processed foods and whole grains is also good. So everyone can do these factors that are related to lifestyle. If you’re at high enough risk, you can add breast MRI and then some women do consider preventative removal of the breast, but that’s in certain very high-risk situations.

Adam: [12:42] Right, right. Wow, that’s really, really great advice. Susan, it’s been great having you on the show. I really appreciate your time and thanks for joining us today.

Dr. Domchek: [12:51] Thank you so much.


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