Genetic Testing and Hereditary Breast Cancer, with Allison Kurian, MD, MSc, FASCO, and Kristen Mahoney Shannon, MS, LCGC

Cancer.Net Podcast

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In this podcast, Dr. Allison Kurian and genetic counselor Kristen Mahoney Shannon talk about what people should know about genetic testing and hereditary breast cancer, including what to expect when meeting with a genetic counselor, ways to reduce your risk of developing cancer, and talking about genetic test results with family.

Dr. Kurian is a Professor of Medicine and of Epidemiology and Population Health at Stanford University School of Medicine, and Director of the Stanford Women’s Clinical Cancer Genetics Program. She is also the 2023 Cancer.Net Specialty Editor for Breast Cancer.

Ms. Shannon is a senior genetic counselor and Director of the Cancer Center Genetics Program and Director of Genetic Counseling for the Massachusetts General Hospital Department of Medicine. She is also a 2023 Cancer.Net Advisory Panelist.

View disclosures for Dr. Kurian and Ms. Shannon at Cancer.Net.

Dr. Allison Kurian: I'm Allison Kurian. I am a professor of medicine, oncology, and epidemiology and population health at Stanford University. And I am speaking today with my colleague, Kristen Shannon, who will introduce herself.

Kristen Shannon: Hi, it's great to be here. My name is Kristen Shannon. I am a genetic counselor and the director of cancer genetics at Massachusetts General Hospital in Boston. And I have no financial relevant disclosures to report.

Dr. Allison Kurian: Thank you, and I have no relevant financial disclosures either. Very good. So today we will be talking about breast cancer and inherited risk and genetic testing. And let me start by providing a definition of a genetic or hereditary condition. So the way we think about this is something that has a high risk for developing a disease, not a certainty, but a high risk, and runs in families, generally because of a genetic finding that we can identify. And that typically is identified through sequencing, testing of blood or saliva samples, and typically allows us to find a change that we know is clearly associated with disease. A good example for breast cancer are the genes BRCA1 and BRCA2, which some may have heard of, and we will talk about further. So that is just an example, and we will get into more of the details of this as we go on. But I think the point is something that runs in families often is seen with the trait, so for BRCA1 or BRCA2, that would be breast cancer or ovarian cancer, affecting people in every generation. And having what we call for these kinds of genes an autosomal dominant inheritance pattern, so inherited from either parent. And taking only 1 copy that is not functioning to give a person higher risk of the condition. So that's sort of a bit of the basics here on genetic or hereditary risk.

And just to give a sense of how common hereditary breast cancer is, we think that in general this may account for, I would say, somewhere between 5% to perhaps 10% of cases of breast cancer. And Kristen, please jump in and tell me if you think differently. But that would be my ballpark. And I think probably the majority of those are the BRCA1 and BRCA2 genes that I mentioned, although there are others that we are recognizing are playing more of a role than we thought, and we'll discuss those, too. So let me give you a chance to continue and respond, Kristen.

Kristen Shannon: Yeah, no, I totally agree. And I was thinking that maybe I could talk a little bit about some of the features that are suggestive that there could be one of these inherited breast cancers in the family, because recognizing these signs of hereditary breast cancer can be super important for early detection and prevention of breast cancer. So first, multiple cases of breast cancer within the family, especially among close relatives like parents, siblings, children, those can be a sign that the cancer is inherited. Another important sign is early age of onset of disease. So breast cancer diagnosed at a young age, typically before the age of 50, might point towards hereditary risk. And it's not always the case, but it's something to be aware of. Also, if there is a history of ovarian cancer in the family, especially if you see it in conjunction with breast cancer cases, that's a significant sign that there could be something inherited in the family. And while it's rarer, male breast cancer can also be associated with hereditary gene mutations. So if there's a history of male breast cancer in the family, it's definitely something to think about in terms of hereditary risk.

Multiple cancer types in the family can also be another clue. It's not always just breast and ovarian cancer. If you see a family history of both breast and ovarian cancer or pancreatic cancer or prostate cancer within the same family, that also might be a sign of an inherited cancer syndrome. For individuals of Ashkenazi Jewish descent, it's worth noting that they have a higher prevalence of certain gene mutations in specific genes, specifically BRCA1 and BRCA2, which Dr. Kurian has mentioned before. So a family of history of breast or ovarian cancer in an Ashkenazi Jewish individual should be noted as a higher sign that this cancer could be due to an inherited gene. And lastly, if someone has had breast cancer in both breasts, that's called bilateral breast cancer, and that might indicate hereditary risk.

It's important, though, to remember that it's not just about any single sign in isolation. You really need to take a look at the bigger picture and the bigger context of the family. So if you notice any of these signs in your family, it's a good idea to seek guidance from a health care professional, like a genetic counselor or a medical oncologist, and they can help assess the family's risk and recommend genetic testing if needed. Dr. Kurian, did I forget anything or leave anything off?

Dr. Allison Kurian: Perfect as always. I will just add a little bit here in terms of the specific gene names that we think about, because sometimes it helps people to have sort of a list in their minds, not that we expect you to remember the whole alphabet soup of these different genes. And let me just say that I think it's always a bit of a hodgepodge, some of these names. I used to wonder how people come up with these names, and often there's a bit of a history there. But I will just go through a few of them. We now have some practice guidelines, and they are basically put together by a group of experts who review all the evidence frequently and come up with recommendations. And so there is a list in these guidelines of basically which genes we think are appropriate to test for breast cancer in families, because there's enough evidence to suggest that.

And so in addition to BRCA1 and BRCA2, the ones that I think of as the most important, and I'll want to hear Kristen's thoughts about this, too, but the ones that we see most often are called ATM. Sounds like a cash machine, unfortunately not, but ATM. CHEK2, C-H-E-K-2, and then one called PALB2, which stands for Partner and Localizer of BRCA2, and is a lot like BRCA2 in its risks.

There are some other genes that give breast cancer risks that are less common. One of them, CDH1, is a gene that also causes an increased risk of stomach cancer. There are a few others that we always keep in mind. There's one called PTEN that's very rare that causes a syndrome called Cowden syndrome that I certainly haven't seen much of. Kristen may have seen more, but it's not something we see often and goes with a lot of other features in families. There are 2 genes that I think we recognize more in recent years and like to be sure we test, called RAD51C and RAD51D, and those both give increased risks. And then another one that I always think of as important here is TP53, and that is a gene that causes something called Li-Fraumeni syndrome, which has probably the highest cancer risks of which we know. There's another one, STK11, that gives some risk, NF1. We see these as being less frequent contributors. Those are the ones that I kind of keep in mind. And again, there will not be a quiz on the alphabet soup, but just so you're aware of what kinds of names you might hear. Kristen, please jump in if I've forgotten any or anything else you want to say.

Kristen Shannon: No, I think that that's important. I think the only thing that I would add is that some people think when they go in for breast cancer genetic testing, they only are getting the BRCA1 and BRCA2 gene. And it's just important for people to realize that that's not really a complete test at this point, as you mentioned, Dr. Kurian.

Dr. Allison Kurian: Totally agree, and thank you.

Kristen Shannon: Should we move into how to prepare for a genetic counseling appointment?

Dr. Allison Kurian: Please, yes.

Kristen Shannon: Sure, okay. So preparing for a genetic counseling appointment for breast cancer risk can be helpful. First and foremost, we suggest that you gather your family health history. So reach out to your relatives and compile as much information as possible about your family's health background. Pay special attention to any instances of breast cancer and ovarian cancer, prostate cancer, pancreatic cancer in the family. And if any family members have had genetic testing, it's really helpful to jot down those test results as well and bring them with you to the appointment. The other thing is to think about your own personal medical history. You know, think about if you've had any past diagnosis, any treatments, surgeries, or medical conditions, especially those related to breast cancer, your genetic counseling appointment will include a discussion of those. The other thing is, you know, if you've had any medical tests related to cancer, it's important to gather those records if they're not already in your hospital's medical record system that you are going to.

Another good idea is to just prepare a list of questions that you might want to have answered. So what do you want to know? Are there specific concerns or specific things you're curious about? It's also important to understand what you want to get out of this genetic counseling encounter. Do you want to just clarify your risk of having a gene? Do you want to consider genetic testing? Or do you want to talk about just managing your risk for breast cancer? That's super important to have that in mind before you actually go into your appointment. Lastly, I would consider bringing along a person, a supportive person with you to the appointment. Having someone with you can help provide emotional support because sometimes these visits can get emotionally charged, but it also can help to have someone remember important details that you will discuss with your health care provider. So it's really important to just arm yourself with information, questions, and support so that the appointment is as productive and informative as it can be. Do you have anything else you'd like to add, Dr. Kurian?

Dr. Allison Kurian: It's wonderful to have your expert perspective on this. And I guess any thoughts about really what's inside the box? I think sometimes people just sort of wonder what's going to happen when I go in that room. Sometimes we have patients come in and say, “What are you guys going to do to me? Will there be surgery done?” And we reassure them that we are not doing anything that wild. And so maybe just a sense of kind of walking people through what will happen when they go to meet with genetic counselors.

Kristen Shannon: Absolutely, thanks for bringing that up. So during the initial meeting, first you'll probably discuss your personal health history, again, any past diagnoses, surgeries, medical conditions. And then typically a genetic counselor or a medical professional will dive right into your family health history. So they'll ask a whole bunch of questions about your close and extended family members to build a really comprehensive picture of your family and the cancer diagnosis in it. They'll want to know if anyone in your family has had cancer, and they'll also want to know what type of cancer that person has had and also the age at which that person was diagnosed. So those are the 3 pieces of information that your health care provider will want to get from you.

The genetic counselor will also probably ask you about what you want to get out of this encounter to make sure that you're both on the same page. Again, do you want genetic testing? You know that already. Or do you want to just talk through the process?

So the big part of the initial meeting is really education. The genetic counselor will explain what Dr. Kurian described at the very outset of this discussion, what's the genetic basis of hereditary breast cancer, including all the specific genes that Dr. Kurian—the alphabet soup that we talked about. Talk about inheritance patterns and the implications of having a genetic mutation. The genetic counselor will probably also first assess your risk of having a mutation in one of the genes, and then they'll also talk to you often about genetic testing. So if genetic testing is on the table and you and the genetic counselor both agree that it's a good step, they'll walk you through the process of informed consent. And so this ensures that you understand what the testing entails, the potential outcomes, the implications of the test results.

And then if you decide to go through with genetic testing, you will provide a blood or a saliva sample. And then it's a waiting game because these test results can take several weeks, usually about 3 to 4 weeks to get the test results back. When the test results come back, you'll typically have a follow-up appointment, either in-person or on the phone with your genetic counselor. And that's when they spend a lot of time interpreting the test results, explain what they mean for you and your health, as well as discussing the appropriate risk management strategies, if necessary. And if a gene mutation is identified, a genetic counselor will guide you on how to manage these risks. But it will depend on the specific mutation that is identified. And then the other thing that the genetic counselor can help with is just the emotional support. Some people have a harder time than others hearing this information. And also to talk about how to tell your family members about this. So in a nutshell, the initial meeting with the genetic counselor is about gathering information, assessing risk, and potentially deciding on whether or not you're going to have genetic testing. And then after that step, it's about interpreting the test results, talking about next steps, and providing emotional support.

Dr. Allison Kurian: Thank you, Kristen. That was wonderful and very complete. And as I was listening to you, first of all, I was thinking about my general admiration for genetic counselors, which is huge. They taught me everything I know about this field. But so also kind of highlighting the key things that a meeting with a genetic counselor will do for you, as you so nicely did. And I think it's getting the right test ordered, making sure that the results make sense to you, and going beyond the patient. But I think those are sort of the key aspects that you communicated really well of the things that we want to get done there.

Kristen Shannon: Well said, well said. And I couldn't agree more.

Dr. Allison Kurian: And what do you think about the family part in terms of how that gets done?

Kristen Shannon: Right, so discussing your genetic test results with family members can be hard and challenging, but it's really, really important. In terms of talking to your family members, I think first, determine the way you're going to notify your family members. So are you going to talk to them? Are you going to send them a letter or an email? And how you share the information may be different based on your relationship with that person. So for example, you may sit down over coffee with a close family member to talk about your test results, but you may choose to write a letter to someone that you don't have that much contact with.

The next thing that I think is really important is to be prepared. So before you even start to have this conversation, make sure that you have a clear understanding of your genetic test results, the implications to you and to the family member. That's super important before you even start to have the conversation so that you can explain things to people in simple terms without too much medical jargon and make sure you keep it straightforward. It's really helpful to have a copy of your genetic test results and to provide that to your relatives if you're comfortable doing so, because then they can take that information with them to their genetic counseling or genetic testing appointment, which can be incredibly essential in terms of making sure that they get the correct test at the right time and the test results are interpreted correctly.

The only other suggestion I have is just to keep in mind that family members are going to react very differently to this information. And some people will be very matter of fact about it. Some people might get a little distracted by this whole thing. So just to be patient with people and keep the conversation open. Allow them to call you if you're willing to do that so that the conversation can develop over time because, you know, really, in the end, the goal is to make sure that everyone in the family is well informed and makes decisions based on their own health and their well-being.

Dr. Allison Kurian: Thank you. I couldn't agree more. And we sometimes, as people may have heard, call this “cascade genetic testing.” So a patient is tested. Somebody who's already had cancer maybe is tested. But then we have the opportunity to have this cascade of beneficial genetic testing, where we can get to people before they have cancer and work on prevention and screening, which I'll talk about in a minute. And I will say that, in general, we here in the United States, and certainly other places as well, don't do as well as we would like with cascade testing despite all best efforts of everyone. And so just to emphasize that family notification is super important, genetic counselors are wonderful at helping people to do that. And I think also additional strategies and interventions are underway to try to help make that easier.

So if I may, I'll talk just a little bit about kind of what we do when we find something. Is that okay to do?

Kristen Shannon: That sounds great. Talk about people, you know, what they can do about their test results.

Dr. Allison Kurian: Good. Yeah, so I always think that's important. I'm an oncologist by training. I'm not a geneticist. And again, it's only thanks to the brilliance of genetic counselors like Kristen that I have learned what I have for the last 2 decades working in the field. But so I tend to think in terms of what can we do to treat this person differently if they have cancer to prevent or reduce the risk of a future cancer. And so what I would say is increasingly over the last few years for a person with breast cancer, as well as some additional cancers, it started to matter what these results are in terms of how we treat the person, whether we might give different medications. And that's really exciting because for years in this field, we didn't have that, and now we do.

And so the drugs that are increasingly important are called PARP, P-A-R-P, inhibitors. And sometimes, if a person has a BRCA1 or BRCA2 gene mutation, we might even offer those drugs to treat a breast cancer or, in other cases, ovarian, prostate, or pancreatic cancer. So I think the testing can matter like never before in terms of what we might do to take care of people's cancer. Sometimes we might also choose a different surgery. So sometimes a woman who has a diagnosis of breast cancer might choose to do a more extensive breast surgery, she might choose a double mastectomy to reduce her risk of getting a second breast cancer. That's never required. She certainly doesn't have to do so extensive a surgery if she doesn't choose, but it is an option that some people might choose. And there might also be other cancer risks to manage in somebody who had breast cancer. BRCA1 and BRCA2, for example, give a high risk of ovarian cancer. And so we might talk with someone about the possibility of removing ovaries to prevent an ovarian cancer, which often is recommended with BRCA1, BRCA2, and other such gene mutations.

I will say that I think for somebody who hasn't had cancer yet, or hopefully ever, particularly as we think about breast cancer, we're often thinking about intensive screening. So starting often earlier than a person would if she didn't have high risk and generally adding magnetic resonance imaging, MRI, to screening with mammogram alone. And that really is, I think, the cornerstone for women at high risk is adding that breast MRI screening. For pretty much all of the genes I mentioned, that would be clinically indicated and covered by insurance and important to do. MRI has no radiation, very effective at finding breast cancer early.

So I think to summarize, it's really all about understanding risk based on a particular gene mutation, understanding if a different kind of treatment is needed for the cancer that a person has, understanding if any sort of preventive measure is needed for future cancer risk, and making sure that the screening we have for breast and for other cancers is appropriate to the level of risk. Anything to add there, Kristen?

Kristen Shannon: No. No, I think that that's great.

Dr. Allison Kurian: Absolutely. Yeah, so I think it's wonderful to have this opportunity to speak about the importance of genetic testing, which is I think more important than it ever has been at this time for the care of patients with breast cancer and their families. And so as we move into breast cancer awareness month, it's great to be able to talk about this. Thanks so much.

Kristen Shannon: Thank you so much. I agree. And if you have any questions, I would suggest you reach out to your doctor or look up on the ASCO website for a referral to a genetic counselor.

ASCO: Thank you, Dr. Kurian and Ms. Shannon. Learn more about hereditary breast cancer and genetic testing at www.cancer.net/hboc.

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