What to Know Down Below™
Welcome to What to Know Down Below™ by Tina’s Wish! We’re here to empower you with the knowledge and tools you need to advocate for your own gynecologic health.
Knowledge is power, and we encourage everyone to join us in learning more about what you need to know, down below!
What to Know Down Below™
The Role Genetics Plays in Gynecologic Cancers
The Role Genetics Plays in Gynecologic Cancers
Featuring:
Susan Domchek, MD; Medical Oncologist, Executive Director of the Basser Center for BRCA, Penn Medicine
Amanda Ganzak, MS, CGS; Lead Genetic Counselor at Yale School of Medicine
Moderated by Leslie Zmugg, General Counsel at Gordon Brothers and a member of the Tina's Wish Boston Gathering Committee.
To learn more about gynecologic health, visit tinaswish.org/whattoknow.
Welcome to What To Know Down Below by Tina's Wish. We're here to empower you with the knowledge and tools you need to advocate for your own gynecologic health. Knowledge is power, and we encourage everyone to join us in learning more about what you need to know down below.
Speaker 2:Hi everyone. My name is Leslie's mug . I'm general counsel at Gordon Brothers, and I'm also a member of the Tina's Wish Boston Gathering Committee. Three years ago, I attended a Tina's Wish event in Boston. It was my first and what I learned that evening changed my life as well as those closest to me. I'd recently received a report through the Ancestral Connection Service 23 and me that I had the BRCA two gene mutation, and then my sister received the same news with one of our two brothers having had prostate cancer. We all of a sudden realized that we had this secret family history that was unknown to us. And from that Tina's wish panel, I was given a roadmap for what to do with that startling new information, which was priceless to me and to my family. So I'm so excited to moderate today's panel because it is personal to me. I'm grateful to Tina's Wish, whose mission it is to find an early detection mechanism for ovarian cancer, for creating this series so that one day all women will have the opportunity to have a fighting chance against this disease. And now let's welcome our panelists. First we have Dr. Susan Domek, medical oncologist and executive director for the Vassar Center for BRCA or BRCA at Penn Medicine.
Speaker 3:Thanks so much for having me.
Speaker 2:Welcome and genetic counselor, Amanda Ganza from Yale School of Medicine.
Speaker 3:Thank you so much for having me here today.
Speaker 2:Thanks to you both, Susan and Amanda. I'm really excited to be here with both of you, and I'm thrilled that I have the opportunity to be in this conversation with you for the next 30 minutes. So, without further ado, let's, let's dig in. Um , we'll start with probably the most burning question for the attendees. Um , and we'll go first to , um, Dr. Domek , what is a genetic mutation Exactly. And if I have one, will I develop cancer?
Speaker 3:Yes. A genetic mutation or if you've seen a recent path , uh, report, it will be called a pathogenic variant. Periodically, we like to change the words just to confuse everyone. Uh, no , that was, that was just a joke. Uh, but , uh, those are synonymous terms, mutation or pathogenic variant. And the different test reports will say things differently, but both of them mean the same thing, which is, as a reminder, the DNA is the, the blueprint, the instruction manual for a cell. And based on what the DNA says, proteins are made. And if there is a mutation or an abnormal variant, pathogenic variant , um, in the DNA , then the protein that is made is not functional. And either it can't bind to things or it isn't expressed at all. And because that protein is not functional, that is what increases cancer risk. So even if you have a mutation , uh, that you're born with, this increases your risk of cancer. But it does not mean that you will get cancer, or as we tend to say, genetics is not destiny. But some of these genetic mutations increase your risk by quite a , quite a great deal. And so it really depends on the specific gene and the specific mutation, what your cancer risks may be. And it's very important to be informed and to talk to people who know the details to get the best information.
Speaker 2:So, so what are the different mutations that one can have ?
Speaker 3:Right. So there are genes that everybody has. So for instance, all of us have BRC one and B RCA A two genes. The normal function of these genes and these proteins in the cell is to help repair your DNA . So actually BRC one and BRC two are good for the cell. But if you have a mutation in one of these genes that leads to the protein not working, that's what causes problems. So mutations in BRA one and BCA two increase your risk of breast cancer with lifetime risks of up to 70%. They increase your risk of ovarian cancer. Those risks are higher for BA one mutations than for BA two mutations. But for BA one, those risks are as high as 45%. These, the mutations in these genes also increase the risk of male breast cancer, prostate cancer, and pancreatic cancer, particularly for BRC two. But those aren't the only genes. Those are the ones that people tend to know the most about because of Angelina Jolie and just a lot of discussion in the media. But there are others. And so there's a syndrome called Lynch syndrome. And Lynch syndrome is associated with mutations in, in , in multiple genes. And this is associated with a high risk of colon cancer, but also endometrial cancer or uterine cancer, which is relevant for our discussion today. And other cancers. Um, there are mutations in genes such as RAD 51 C , RAD 50 1D and B brip . And these , um, increase your risk of ovarian cancer, but more like in the 10% range, which is still significantly higher , uh, given the difficulty with ovarian cancer. And there are other , uh, uh, mutations in , in rare genes that probably we won't get into today. Uh, but there's a range of genes and a range of risk . And that's why it's important , uh, to know exactly what you're being tested for and exactly what the implications are when these mutations are found.
Speaker 2:So , um, let's unpack. There's so much to unpack in, in all of that information. I think I found in my journey, one of the , um, points of misunderstanding is that men cannot inherit those genes. Um, can you, can you tell us what the truth is behind that statement?
Speaker 3:Absolutely. And I'm sure Amanda's gonna touch on this , uh, uh, additionally , um, when she's talking about the role of counselors, for whatever reason , um, women, men and their physicians often really look to the mother side of the family when we're talking about, if you will, female cancers. Um, but when you take a step back, if you line up all the BRA one mutation carriers in the world, half of them will be men. Okay ? And half of the time when we find an individual who has a BRC one or two mutation, she has inherited that mutation from her father. In addition, there are risks to men. Um , those, these risks are different and they're not as significant , uh, meaning in terms of an absolute number, but they matter quite a bit. And particularly for BRC too , there's a significantly increased risk for male breast cancer with a lifetime risk of up to 10%. That might not sound like very much, but the baseline risk in the population is 0.1%. So you get the idea, this is a massive elevation of risk. There is an increased risk of prostate cancer, and this is the type of prostate cancer that's aggressive. Or as we say, it's the type of cancer that you die of, not that you die with. It's not benign prostate cancer. And again, this increased risk of , uh, pancreatic cancer, which we've talked about, which affects , uh, both men and women. Uh , so these risks are significant. And in addition, if one has a BRC one or two mutation, there's a 50% chance that that could be passed along to each individual child. Uh, so this is really important, not only for the man, but also for their family.
Speaker 2:Well , thank you for that. And you touched on the role of a genetic counselor. For me in my journey that was so important. Um, I , I don't think that I was fully aware that that function existed, that that source of help existed. So, Amanda, tell us what , um, is the role of a genetic counselor?
Speaker 4:Absolutely. And that's probably the the first question I always ask patients when they walk through the door, you know, this is probably the first time you ever heard of a genetic counselor, and you have no idea what you're about to experience. So let me just give you a quick recap. But basically how I start every time I meet with a new patient. So I see my role and my function in patient care is really , um, helping patients to provide 'em with education, to guide and support them. Through this journey of learning about inherited cancer risks and pursuing genetic testing, I'm really there to help translate those technical genetic terms in a friendly and understandable way so that patients walk away understanding this is my risk, and this is what it's gonna mean for me, for my children, for my family. And that they can then communicate that easily because they understand it , um, from our conversations , um, so that their family members can and themselves use that information as an opportunity to , um, go after. And , uh, you know, future screening and cancer prevention strategies and planning, all of that information can really be , um, obtained once , uh, really once that , uh, patient has a true understanding of what genetics mean and whether , uh, mutation and how does this impact myself and my family. And I'm really there to help alongside the patient, walk them through that process. Um, I also see myself as , uh, there to help identify resources. So patient advocacy groups and other families that I can get them in touch with, that they can talk to and, you know, can be there for them as, you know, going through with them or having gone through it before to give them some advice or to go through some research opportunities that they might be eligible for, that they might not have been aware of otherwise. So I sort of see myself in that way too, to open other doors that they might not have realized were even there.
Speaker 2:Um , and that was my experience too. Um, so how do people determine if they and their family are at high risk for cancer? And if they would benefit from , uh, a specific assessment, a genetics evaluation, and then a risk assessment?
Speaker 4:Yeah, so I, I always tell patients , uh, ask your family first. The, the really important step in the beginning is gathering as much details as possible. And in some families, that's not possible. People are adopted or they've lost touch with family. Um , but , uh, you know, I try to get some people to do some homework before they come into their first visit because as much detailed information that we have about the types of cancers in the family who was affected, how old were they when they were diagnosed, are all important information that we use to provide an accurate risk assessment for an individual. Um, so kind of doing that homework in advance really helps us understand who's gonna be best suited for a genetics evaluation. Um, and for most people, I would say, if you are concerned about your risk for cancer, meeting with a cancer genetic specialist is a really the best first step. Have us look at someone's personal and family history in detail, really give them a good idea. Is this something we need to be worried about or not? Um, and in general, the families that are kind of higher risk for us for a hereditary cancer risk are those where we're starting to see the same or related types of cancers on the same side of the family, like breast and ovarian cancer clustering together. Um, young onset cancers like breast cancer before the age of 50. Um, more rare cancers like ovarian cancer or pancreatic cancer, regardless of kind of what a , what are the family history or the age in which they were diagnosed. And even in some individuals with certain ancestral backgrounds such as Ashkenazi, Jewish ancestry, also have a higher risk. So when we start to see some of those patterns in someone's family history, those are the people who we really say would benefit the most. And even people who might not hit all those highlights, they still might be , uh, you know, kind of worth meeting with a counselor and a genetics professional to really have a better understanding of what their risk might look like.
Speaker 2:Dr. Domek, what percentage of gynecologic cancer patients have a genetic mutation?
Speaker 3:Yeah , it , it, a little bit depends on how you count , uh, to, to, to be honest. And , uh, we always have these conversations that if you test for more genes, you find more stuff, whether or not it's related to the cancer at hand. But to give some sort of rough estimates , uh, for ovarian cancer, it's in the range of about 15%. Uh, when we're talking about , uh, uterine cancer, it's probably more in the 3% range. Uh , cervical cancer is not , uh, closely is not known to be associated with inherited cancer susceptibility. Uh, it is more strongly linked to , to HBV and environmental , uh, causes. Um, and , uh, and so it is really important, as you know, Amanda has, has , uh, outlined to know the details of a person's family and personal history, because ovarian cancer, when I'm talking about ovarian cancer here, I'm, I'm talking really about epithelial ovarian cancer, sort of, if you will, the , uh, the , the more common cancer. But there are some rare ovarian cancer types that are associated with other gene mutations. And so that's why as part of this , um, uh, assessment , um, that a lot of information will be obtained, I'm sure we're gonna talk about later, you know, about the fact that, you know, in the Ashkenazi Jewish community, one in 40 individuals of Ashkenazi Jewish descent does have a mutation in VRC one or two . And so that is one of the situations where , um, we remain , uh, that family history may not be the most important thing as ethnicity. Um, it's all , it's still important. It's still more likely that if you have a family history and you're Ashkenazi Jewish , uh, that , uh, you have a mutation. Well,
Speaker 2:Let's talk about insurance , um, and how that plays into it because it is very relevant. Mm-hmm <affirmative> . Um, when we're talking about, you know, putting the word out and encouraging people to go get tested, particularly when you, like I have had a diagnosis , um, should people be concerned if they , um, you know, for example, are young, don't yet have their own personal insurance, they'll then have a preexisting condition. Um, what do you think about that and what can you advise people to do?
Speaker 4:Yeah, so there are , um, discrimination laws that are in place both federally and Statewise, that provide some level of protection from discrimination based on results of genetic testing. One of the larger federal laws is called the Genetic Information Non-Discrimination Act, or GINA for short. Um, there's a wonderful website , um, that you can go to as well to learn more information , um, about Gina and what it protections it provides, but also protections that it doesn't provide. It's not a perfect law. Um, I think where it falls short is really when it comes to , um, life insurance, long-term care or disability insurance. That's really where Gina does not provide protection a , against results of genetic testing. Um , as well as those individuals who might be looking to serve in the active military results of genetic testing can be used to decide about fitness or eligibility for the military. So though that's really where Gina , um, I think doesn't always provide the best protection. And so for patients who might be worried about that or concerned about that prior to genetic testing, it might be worth them kind of learning a little bit more about those laws, maybe obtaining some of those policies beforehand. So they feel like they've done at least as much as they can do to control that part of it. Um, but Gina does provide protection for employment and , um, health insurance discrimination. So under that part of it , um, it would not be deemed a preexisting condition for people who have , um, no personal diagnosis, but just have a, a genetic test result that shows a mutation putting them at increased risk for cancer.
Speaker 2:Can you explain if insurance covers genetic testing and then in the cases where it doesn't, what are the other options available to get tested?
Speaker 4:Yeah, so most insurance companies do cover the cost of genetic testing, particularly when people are meeting their insurance criteria for genetic testing. So some of those risk factors we talked about earlier, like family history of ovarian cancer or young onset cancers, or all factors that are looked at in terms of deciding about coverage. Now for those individuals who might not meet those criteria , um, or are just interested in pursuing genetic testing to understand their risks , and they might have no information about their family history, there are more affordable ways nowadays to pay for the test out of pocket , some of which costing around $250. And so healthcare providers can help navigate those decisions and help determine if insurance coverage would be , um, available or whether those out-of-pocket options might be ones that a patient might want to pursue. But it's a lot less than the thousands of dollars for testing that we used to hear about many years ago.
Speaker 2:What do you think about , um, the age, you know, is there sort of a , a point in time before which you wouldn't encourage someone to get tested?
Speaker 3:Yes . So , uh, our general philosophy for, for instance, BRCA one and BRC two is that particularly if there's a known mutation in the family , uh, we suggest that women be tested at 25 because that's when we start breast MRI screening. But we do not test children , um, for BRA one and two mutations. And the reason for that is because at this time that's, there's no actionable utility for it. Meaning we don't do anything different in children who would have BRA one or two mutations, and therefore there's no reason to know, and this is an adult onset condition. So there is a concept of autonomy that individual gets to make the decision about when they want to know that information. We definitely have young women, you know, 18, 20 21, come in to talk to us, and sometimes when we review that, we're not going to do anything till 25. They say, thank you very much, I'll see you in a few years. And sometimes they do really want to know this information because they feel like they, they feel like they already have the mutation, there was a 50% chance they don't. But we are very careful to review sort of the pros and cons. It depends on the gene. So for instance, RAD 51 C and D , the risks are later. So we don't necessarily test , uh, as early and for Lynch syndrome. There, there are are different approaches there because of the colon cancer screening. And so there's not sort of a one size fits all approach. It depends on the gene. What I can tell you though, that if, if it's a breast ovarian type of situation , um, and no one's in the family been tested, you know, 25 is usually , uh, when we, we talk about it. And Amanda, I don't know if you wanna say specific comments on Lynch syndrome since you know, I'm outta my, over my skis . <laugh> .
Speaker 4:Yeah. So I, I think for , uh, you know , a syndrome like Lynch syndrome or other colon cancer type related conditions where we see increased risk, also linked with gynecologic risk , um, we look at the family history in combination with the gene in particular. So there are some genes for Lynch syndrome where you can see people much younger with colon cancer, where we would start screening with colonoscopy maybe as early as 20 or 25, depending, especially if we see someone in the family who might have been diagnosed in their late twenties or early thirties with colon cancer. So , um, we really, as part of that big risk assessment and, you know, really wanna hit home, why knowing your family history can be so important is , um, while the general guidelines might say 20 to 25, we might alter that depending on family history, if we really saw as a much younger case of colon cancer and would need to start even earlier than that to , to be on the cautious side. So , um, you know, it really can, can depend, but really in generally try, you know, I I really have not tested many kids, if at all , um, for any of this, unless there was, you know, a sort of an outlier in a family history.
Speaker 3:And, and I wanted to make, you know, one other important, important or two, two points that are quite important. One is that, you know, we mentioned individuals of Ashkenazi Jewish ancestry, but we wanna be clear that , uh, uh, these gene mutations can be seen in individuals of any race and any ethnicity. And we're very conscious of the fact that there's under testing in , um, in minority populations. Uh, so we're really conscious about equity and fairness and making sure that individuals know of all races and ethnicity know that if you have a family history, you should, you should get tested. And the second issue is that if you have a strong family history and testing is negative, that doesn't mean you're off the hook. Uh, we still that your family history drives things. Um, the , with the , the one exception is if there's a known mutation in the family and you don't have it, that's the one time where we're really reassuring. But if there's a very strong family history and there's negative genetic testing, we still change management and we increase surveillance based on the family history alone.
Speaker 2:Um, we're talking about testing then. Um, are all tests created equal? I guess my first encounter with a a test was 23 in May . Um, I thought I was seeing things when I got the report back , um, but then I followed up with my gynecologist and retested. Um, what do you think about the commercially available , um, consumer self-administered tests?
Speaker 4:Um, you know, I think you said it , they're not all genetic tests are , are created equal. And I think we advise and really caution the use of commercially available tests that you might find at your local pharmacy or on Amazon , um, in terms of guiding medical decisions and, and learning about risk for different diseases such as cancer. Um, you know, they, they, they do a certain thing , um, but it's not maybe as, you know, as comprehensive as the type of testing that you , um, might receive when you see a genetic counselor or a genetic provider who's ordering a clinically available genetic test. And I think where I caution most is there are so many risk factors that go into understanding someone's personalized risk. Part of that is family history. Part of that is results of genetic testing. And so we have to look at all of that together. And those direct to consumer type tests don't really give us that full comprehensive view from the genetic test standpoint. And so what I fear is that patients might utilize the results that were negative through this commercially available to and feel reassured when it might not have been the best or most accurate test that they should have received. And so they might not be then getting the screening that they need. They might not even tell their doctor about their family history 'cause they feel like I got a negative genetic test and I'm fine. Um, and so I think I caution a little bit the use of that. Um, and, you know, your , your doctor did the , the right thing and what definitely what I would have recommended too . Okay, let's, let's confirm that through a clinical test. Let's see if there's any additional testing that might be indicated based on personal or family history factors. Use all of that together to make a plan as to what we need to do , um, in terms of screening, understanding your risk and how to communicate that to the family, whether the results were positive or negative.
Speaker 3:And, and , and as Amanda pointed out, but this is one that we really like to drive home , uh, 23 and me, for instance, only test is test for the three common found , what we call founder mutations in the Ashkenazi Jewish population. So I literally have had my own family members say I had 23 and me test , and it was negative for B say one and two mutations. And I'm like, that's great. You're Italian. Uh , that didn't help you. Uh, you're not of Ashkenazi Jewish descent. So, you know, I've had extremely smart people not understand what the test was. So, so that's the key. I think no matter what, you have to understand what test is being sent and what information you're getting at it. There are these other tests that, that Amanda will, I'm sure it'll come up later, but there are these things that we kind of call , uh, a company facilitated test , consumer facilitated test , where you can actually reach out to a company, say you want to be tested, and they will find a doctor for you. And they are more comprehensive tests, but the downside of them then is that it's completely taken out of your medical plan. Um, and so, you know, the best way to use genetic testing information is to embed it , uh, with the rest of your medical information and your medical records. Um, you know, it's a piece of information that's really valuable. So if you put it outside of the medical system, then we're not optimizing the information.
Speaker 2:So we have a couple questions that have come in from the audience. Um, one is, what does the physical testing process look like? For example, is it a cheek swab, a blood sample, or something else?
Speaker 4:Yeah, so we , um, can, can do the testing through blood is probably the more traditional way that we've done them. Saliva is just the same, just as accurate. Um, some labs will offer a cheek swab, but it's not as common as the saliva based test where you're spitting into a tube. I always tell patients it's not glamorous, but it'll get the job done. Um, and so we can use either type of an approach to do genetic testing.
Speaker 2:Okay . Um, and one other really good question that I think we should ask now is , um, are there any lifestyle habits or medications that increase an individual's risk for developing gynecologic cancers?
Speaker 3:So we know that in general, things that can decrease your risk of cancer overall are a healthy lifestyle, including maintaining a healthy weight, regular exercise , um, uh, uh, maintain a healthy weight , uh, regular exercise, and , uh, minimizing your alcohol consumption as well as not smoking. So these are things that we say over and over again , uh, but are really important. And , uh, particularly exercise is important and none of us get enough of it, and we all have to keep at it. Um, for ovarian cancer in particular, birth control pills , uh, oral contraceptive pills have been shown to decrease the risk of ovarian cancer. Um, and so this is an important thing. Having children , um, can , uh, definitely impact certain cancer types. Uh , but it's a little bit complicated and also it's not something that I would ever prescribe to anyone. You know, please have this many children by this age. Um, so it's an association without necessarily being , um, particularly helpful to us. You know, what's interesting is that there are things that are great about developed countries like the United States that are just terrific from the , the , the standpoint of , uh, uh, empowering women that can be negative in terms of cancer risk. So for instance, you know, getting your period earlier and having your period late and having your kids late, that all increases your risk of breast cancer. But those are all things that happen in the developed countries because we're well nourished, so we get our periods earlier, we're educated, so we have our children later. And so, you know, these are things that we just have to balance out and and realize. But again, the things that people have most control over are those , uh, you know , um, uh, healthy weight, regular exercise, minimize alcohol, don't smoke, and birth control pills can be , uh, effective.
Speaker 2:How about sugar? I've heard , um, eliminate sugar. Cancer loves sugar,
Speaker 3:It's been shown in mice. Um, I like chocolate.
Speaker 2:So I, I think with all of that we're just about past our time. Um, I would put it back to the both of you. I, I've so enjoyed speaking to you and hearing , um, uh, all of this information and I'm, I'm sure that our attendees have done so as well. Is there anything else that, that we didn't cover that you think is really important for everybody to understand?
Speaker 3:Uh , well, I'll , I'll have , uh, one comment, which is , uh, I don't know if we hit it hard enough, but I'm gonna say it very precisely. If you are diagnosed with ovarian cancer, you should have had genetic testing for inherited susceptibility. And if you have not, you should get it and you can ask your doctor. But there's lots of different ways to do this. And so sort of don't relent it is an absolute guideline , uh, that all people with ovarian cancer should have had this testing. Um, and , uh, and I'll , I'll let , uh, again, Amanda talk about there are specific things for uterine cancer as well.
Speaker 4:Yeah, I mean, if it's a young onset uterine cancer before age 50, even with no family history would be indicated to do the test. Um, but I also would , uh, empower the women who might have a family history. So maybe if that member of your family with ovarian or uterine cancer is deceased or unwilling to do testing, it doesn't exclude that individual from going forward with the test themselves.
Speaker 2:Well, thank you both so much for being here. Um, on behalf of Tina's Wish , um, and myself, thank you so much for being here. Um, Amanda Ganek and Dr. Susan Domek . Um, and , uh, thank you so much.
Speaker 1:For more information about gynecologic health, visit tina's wish.org/what to know . That's tina's wish.org/w O-K-N-O-W. And like, follow or subscribe wherever you listen to your favorite podcasts.