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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</