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Speaker 1: Pushkin.
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Speaker 2: This show is not a substitute for professional medical advice, diagnosis, or treatment. It is for informational purposes. Please consult your healthcare professional with any medical questions.
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Speaker 1: My mom was diagnosed with breast cancer in her fifties. Luckily, it wasn't complicated and she quickly went into remission. But this April, she was diagnosed with pancreatic cancer, one of the most lethal and hardest cancers to treat. It was devastating news. I assumed it wasn't a hereditary cancer. Most aren't, but some cancers can be caused by genetic mutations like the Brca one and Brca two genes, sometimes referred to as the Braca genes. These are genes that normally protect cells from damage, but when they don't work, cancerous skyrockets. Years ago, I was actually testing myself for Brocca mutations. I sent off blood work for genetic testing with a private company. I never got the results back, and I sort of forgot about it. That is until my mom's doctors tested her blood and found out that she carried a Broco one mutation. Her cancer had a genetic heritable element. I contacted the testing company that I had sent my blood work to years earlier, and I finally got those results. I was positive for a BRCA one mutation. Myself, I would have been livid. If I wasn't so scared. I'd already had my own battle with HPV related cancer in twenty twenty one, and as a pelvic surgeon, I know too well the realities of ovarian cancer. Within weeks, I had my ovaries and fallopian tubes removed. The wildest part. I have a PhD in genetics. I worked with some of the best vision icians and scientists in the world. I am an expert in ovarian cancer, yet this potentially fatal mutation when undetected in me for nearly sixty three years. I'm doctor Elizabeth Pointer. And this is Decoding Women's Health, a show from Pushkin Industries and the Atria Health Institute. This elevating the conversation about women's health in midlife and frankly challenging some of the status quote information out there.
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Speaker 3: As a medical and cologist, I was really interested in breast cancer and I was seeing so many young women with breast cancer and a family history, so trying to help people not have to face these terrible situations that they found themselves in was really compelling to me. So it was really being able to see how devastating this can be in families and at the same time, how he doesn't have to be.
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Speaker 1: That's doctor Susan Domchuk. She's the executive director of the Bachsor Center for Braka at the Universe Pennsylvania. She's an oncologist who specializes in research, treatment, and prevention of BRCA related cancers. I wanted to have her on the show to talk about the importance of knowing your family history, when you should get tested, who should get tested, and what to do if you, like me, discover you carry a BRACA mutation. I realize that this can be a really scary topic for people, but I hope you leave this conversation like I did, feeling empowered. There are so many ways we can be proactive about our health, and simply having more information can make a big impact. So what do women need to know about their family history? Is that three generations back? You know? Sometimes when I take a family history, people will say, Oh, my immediate family doesn't have any cancer, but I have some aunts and uncles that may have had cancer. So what do women need to know about their family history.
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Speaker 3: So this is such an important point, is knowing your family history and knowing this in more detail than previously has been understood. It's important to know who had cancer at what ages, going back three generations, as we say, so looking at cousins and grandparents and more distant relatives is extremely important. The second thing is that it's not just breast cancer. For br SA one and ber C two, those stand for breast cancer one and breast cancer two because we're just not creative, so BRCA one and BRSA two. But when we speak about those two specific genes, which are the most common cause of reditary breast and ovarian cancer, the cancers that are seen are breast cancer, ovarian cancer, pancreatic cancer, and prostate cancer. So really having a complete understanding. In addition, as you're alluding to, people in past generations didn't necessarily talk about cancer, so finding out why Aunt Martha died at forty is really important even if the family didn't talk about it. So having an open conversation with your relatives about the family history. And by the way, genetics isn't just about BERC one and two. People die of colon cancer and they're in colon cancer susceptibility genes, there's early onset cardiovasclar issues. And finally, individuals who are Ashkenazi Jewish descent have a much higher chance of having a BRC one or two mutation. That risk is one in forty as opposed to one in two hundred in the general population. So knowing your ethnicity, knowing your family history are all really important.
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Speaker 1: Let's tat a little bit about if a Broka wan or brock A two gene mutation is being passed down the father side of the family, it can be a little bit more challenging to look at, right because your father is not going to get ovarian cancer. He may get breast cancer, but it can make it a little bit more challenging to look at these family histories and interpret them. Can you just talk about that a little bit.
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Speaker 3: In the past, people felt that it was only the mother's side that mattered, that it was only breast cancer that mattered when you were thinking about family history and the risk of having a genetic susceptibility. But none of that is true. You're really looking at both sides of the family. Fifty percent of all cancer genetic susceptibility genes. They will come from the dad, not the mom. If you line up every r C mutation carry in the world, half our men. And we can't emphasize this point enough since it's so often missed. So we can see families which are really male dominated in which there's a ton of early on set prostate cancer, and that is justice concerning. It's also important to recognize that family size matters. So if it's just your dad and he was an only child and his father was an only child, cancer susceptibility genes can be hidden in those types of families. I want to also emphasize, and this may be a different point, that we have lower and lower thresholds to do genetic testing all the time, so sometimes we get a little caught up in these issues of the exact family history that we meet for genetic testing. But really it's just a matter of knowing anything about your family history, including well, I have a tiny family on my dad's side and I am concerned about having a genetic susceptibility for whatever reason. We also recognize that not everybody knows their family history if they're adopted, or for instance, the Holocaust may have taken out an entire generation, so we have a much lower threshold for testing in those situations.
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Speaker 1: When we talk about this generic genetic testing for cancer, what are we talking about in.
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Speaker 3: The old days, if you will, you know, fifteen years ago, we would be testing for two genes, generally BARC one and br C two. But what we've learned since the nineties is that there are other genes that are also associated with breast cancer. One of those is pretty like beer, say one and two. It's called PALBI two. But there are some other genes, notably genes called CHECK two and ATM, which increase your risk of breast cancer only modestly. So with beer, say one and two, that lifetime risk is seventy percent, with check two it's about twenty to twenty five percent. So now when people get genetic testing, they are almost never tested for just two genes. They're tested for a panel of genes that will include not only beer say one and two, but other genes associated with breast cancer risk. There's colon cancer susceptibility genes as well. There's kidney cancer susceptibility genes. So in general, we send sort of a panel of genes that hits the most common cancers. The specific genes on those panels are looking for what we call a pathogenic variant otherwise and as a mutation in a gene that basically makes the protein not function and that's what increases the risk of cancer.
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Speaker 1: And these genes that we're testing for are pretty much all what we call tumor suppressor genes.
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Speaker 3: Correct. That's correct. So what we mean by that is that all of us are born with two copies of each gene and in general cancer sceptibility genes. Say, beer SA one is good. Beer C one actually helps ourselves repair a specific type of DNA damage called bubble strand and break. So BERSA one and ber C two are good for us. They help us. It's only when we lose them where you are at increased risk or cancer.
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Speaker 1: I just want to pause for a moment here and walk you through this. These concepts can feel so overwhelming and frankly terrifying for women who are trying to better understand their family history and their own risk. So you might have been surprised to hear doctor Domchek say Brako one and Broko two are good for us. But she's right, Broca genes aren't cancer causing genes. They're cancer preventing genes. They're actually helpful. They protect us by fixing damaged DNA. Like doctor John Chuck said, we're all born with two copies of those genes. People with Brocca mutations have a broken copy of the gene. Most of the time, that one working copy is enough to keep you safe, but if something happens to damage or turn off that second working copy, then you don't have any protection. When working properly, these genes literally suppress tumors. You can imagine. It's almost like having security guards that keep cancer from getting in. Only when you lose both guards can cancer develop. Briefly, what can you tell us about the biology of inherited cancers. They're a little different. They present a little bit earlier, so people a little bit younger when they're diagnosed, and they may have a little bit of a better outcome to treatment. Correct.
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Speaker 3: Yeah, it's a great point, and this is where not all genetic susceptibility is equal. BRSA one is different than Chuck two. And the reason I emphasize this is because when we lump it all together, patients can make decisions that may not make sense for them. So it's really important to get gene specific information. BRSA one and two related cancers generally do occur earlier. The median onset of the cancers is in the early forties. But you're right that these tumors for BARSA one and two do seem to be more sensitive to chemotherapy, and so specifically, an ovarian cancer outcome is better with ovarian cancer if you have a br SA one art mutation. In breast cancer, it's kind of complicated because of the different types of breast cancer, but in ovarian cancer that prognosis is clearly better if you have a BRSA one on mutation. So the reason people with cancer should be tested is because we have drugs available that we can give them that will make their cancer do better. Every single person with ovarian cancer needs to have testing. Every single person with pancreatic cancer, with metastatic prostate cancer. That's enough. We don't have to think for a minute about family history. Those are sufficient for people to get genetic testing for breast cancer. Absolutely, anyone under fifty and more recently sort of anyone under sixty five is a candidate for genetic testing, and anyone with a certain type of breast cancer called triple negative breast cancer should get genetic testing. We should not leave a single person in those categories behind. They should all get genetic testing. At big academic medical centers. We're doing better and better. We keep track of our metrics, and we're at over eighty percent in any of those, but across the country those numbers are terrible. For ovarian cancer, it's under fifty percent, and it's hard to imagine why that is, because it actually helps us make decisions about therapy. So if anyone out there that's listening, if you fall into any of those groups, or any of your family members DOE, you absolutely should get genic testing.
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Speaker 1: Let's face it, getting a cancer diagnosis is devastating, but a better understanding of any underlying genetic cause can significantly improve treatment outcomes coming up. If genetic testing can save lives, why are we all getting it done? Decoding women's health will be right back. Welcome back to Decoding women's health. You might be surprised to learn, as I was, that even when genetic testing is offered, many people are slow to take it up. Doctor Susan Donchek has been engaged in some really important work around this.
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Speaker 3: Increasingly, there's discussion about what we call population screening, which is offering everybody if you will be or s one and two testing. The complications with that is that it's not entirely clear how many people really want to do that right now, and also how we actually will get it done. We've done some studies to offer genetic testing to if you will, anyone who's of Ashkenazi Jewish descent. The uptake wasn't as much as we thought. We did a study a few years ago testing about four thousand individuals in that situation, and they didn't have to have any family history. We thought it would take about three months to test four thousand people in for cities, and it took us three years. And other data have really suggested that it matters if your doctor recommends this to you. And this is why this is so important to get out. We need to educate patients people out there in the community about the potential risk, and we also need to educate for to have a really low threshold to do genetic testing if there's a family history or again if people are of Ashkenazi Jewish to sent we're just going to the electronic health record and pulling out individuals who've told their providers that they have a family history and sending them messages saying you should consider getting genetic testing. And just in our preliminary data, just that simple effort, twenty five percent of people schedule appointments to get genetic testing. So people are interested, they just don't know about it. I think that we can use simple solutions of asking people at the right time and then immediately referring them to genetics. Our primary care doctors have a lot to do, so this idea that we can expect them to also do a great screening for these things and get people tested. It might happen, but it's a lot we need to help our primary care doctors.
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Speaker 1: About what age did you start to consider genetic testing? Twenty two to twenty five.
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Speaker 3: There's really two reasons to test. The first reason is because you're going to change your medical decision making, and for most cancer susceptibility genes, you know, we don't start doing anything different medically until age twenty five. That's when we start. For instance, restmeris for BERC one mutation cares. Now, there are sometimes where there's a particularly early onset in the family where we would potentially do it earlier, but in general, we have twenty five in our heads. There's another reason to get genetic testing for BRSA one two and other cancer sceptibility genes, and that's for reproductive decision making, and that takes on two different pieces. One pre implantation genetic testing, So this is when individuals go through in vitro fertilization, screen the embryos and only reimplant the embryos that don't have the BRC one or BRC two mutation. Well, some people are not interested in this, but this technology is available. So there are times that you know, women are interested in starting their families before their twenty five So that's another reason to consider screening. In addition, several of the genes that we're talking about, and I'll give br C two as an example. In rare situations, a baby can inherit two bad copies of ber C two, one from each parent, and when that occurs, there's a twenty five percent chance that the baby will have a condition called fincnianemia, which is a serious medical condition. So these are all reasons to consider genetic testing sort of at the time you're starting to think about your family or medical decision making, and so that matters for the men too, because in general, we don't really start much for men in terms of their personal screening until closer to forty, but when they're ready to start having their children. If one of their parents has a BERC mutation, then we certainly talk about screening before they start having their kids. So I think it's really important that people know that even if their doctor doesn't bring it up, that it still may be real to them, and that they can either talk to their doctors about it they're gynecologists, a primary care doctor, or see a genetic counselor for testing. There are also direct to consumer approaches to genetic testing, where people can just go online and order the tests themselves. There are pros and cons to those approaches, but right now you know it's all hands on deck. There are multiple ways to get this testing done, and we should make sure that people know about all of them.
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Speaker 1: I took the direct to consumer route myself. There are plenty of companies that offer easy to use at home testing kits that you can just mail in and get the results online. The benefit is that it's quick, easy, and relatively inexpensive. The problem is is that you don't have guidance and support necessarily that comes with getting tested with a personal physician. So if you go this route, I strongly advise connecting with the genetic counselor beforehand. Even if you think that you're prepared to learn that you carry a genetic mutation, actually getting that result can still pack a huge emotional punch. Having an expert in your corner helps you understand what the result means and what steps to take next. The National Society of Genetic Counselors has a registry where you can find professionals to guide you. Having said that, in an ideal world, everyone would be guided through genetic testing in person by a physician they trust, but one of the barriers to this sort of testing for many patients is cost. In some cases, patients can get the testing paid for by their insurance. The National Comprehensive Cancer Network provides guidelines for testing that include the big factors that we've discussed today, If you're of Ashkenizi Jewish descent, if you've had blood relatives with a confirmed cancer causing gene variant, or if you or a family member has a personal history of a rare or multiple cancers. I asked doctor Domchek, what about patients are women who don't fall into these categories.
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Speaker 3: If people don't meet those guidelines at most labs, there are still self pay options that cost about three hundred dollars. But I will say that navigating this can sometimes be frustrating and complex for patients. So I think that when people meet clear criteria for JANK testing, everything goes through very well. If people are more on the bubble, self pay options are actually going to be cheaper than if you will going through insurance where it may not be covered at.
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Speaker 1: All, for people who may not be able to afford the three hundred dollars. Are you aware of any support services for these individuals?
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Speaker 3: Yes, there are, and oftentimes the labs have held there are various programs that exist. It does get a little bit complicated if people do not have insurance at all. It can be tricky because even if we could get someone free testing, we're not able to then get them the medical care that they need. So that is a big gap right now. Is people who are completely uninsured. We really do struggle because even if we could test them, we would not really be able to care for them, and that doesn't feel great. So hopefully all insurance problems in the United States will be fixed and we won't have to worry about it. But I'm not going to hold my breath right now for that.
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Speaker 1: So a lot of upside to genetic testing allowing you to do some planning, and we'll move into that in just a moment.
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Speaker 3: Any downsides, Sure, this is information that can be extremely difficult to learn. I had a physician once tell me she felt that the genetic testing both saved your life had ruined it. And she didn't really mean ruin it, but she just at dealing with this information making the decisions she had to make well really difficult. And so, first of all, we always like to emphasize that when you get your genetic test result back, if it's positive, that was always there. You were positive from the time you were born. You know, you didn't change on a dime day to day. We also like to talk about lifetime risks. So when we talk about lifetime risk of cancer as highly seventy percent, that's not your risk tomorrow, that's your risk over your whole life. But you can imagine that feeling getting that information is really overwhelming, and so our job is to try to counsel people through it. To focus on the immediate next steps of what needs to happen. Currently, the only effective strategy for a varying cancer risk reduction is early surgery, so premenopausal to me removable of your ovaries before you or otherwise we go into menopause, and that has significant issues for women. We try to get people through it as best we can, but it's still fun to have to consider these things and then deciding whether to continue to screen or do astectomy. That can be challenging for parents to get tested. We see a lot that when individuals get tested that have children, they can feel very sad and sometimes guilty about the potential that they've passed this belong to their children. Of course, we all pass along good and bad genes to our kids. In this case, you just kind of know what it is. But these are real issues that we know that people struggle with, and our job is to try to help people through this time and really focus on the fact that this information can be life saving, but at the same time acknowledge the grief that's involved in having to make these decisions.
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Speaker 1: So I'm diagnosed with the bracket one mutation in twenty twenty five, what does taking action look like as a younger woman, as a primin apausal woman.
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Speaker 3: Yes, and so in twenty twenty five, there are clear things that women can do, but we are actively hoping for better options. So right now, at twenty five, all someone needs to do is get a breast MRI once a year. The risk of developing breast cancer prior to age thirty when you're a twenty five year old beer C one mutation carries less than five percent, but that's still much higher than an average woman. So brust emri once a year. At thirty, we have to mammogram, so that every six months you're getting an MRI or a mammogram. Unfortunately, between age thirty five and forty women should undergo remove all the pilopian tubes and ovaries. So this is for bars one now. Risk reducing mass tec to me or prophylactic masks tec to me can be done at any time with an individual with a br c in one or two or other gene mutations. Some women are not interested in mask tec tomy at all and will continue screening, so we like to have an honest conversation about their goals about body image, about sexuality, and other quality of life issues as people make their decisions.
00:24:50
Speaker 1: What about just removal of the pelopian tubes alone, without removing the ovaries. Is that data mature enough for us to make that recommendation now?
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Speaker 3: Not? Yeah, but boy, I want it to be.
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Speaker 1: So.
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Speaker 3: The theory behind this, as you're alluding to, is that there's data that many ovarian cancers arise in the philopian tube and that potentially if we just remove the philippian tubes, we can decrease the risk of ovarian cancer. And there's some interesting sort of data out there, including a study that's being done in British Columbia where every woman who's coming in to have her tubes tied just has their tubes removed, and again the very early data suggests that there's a decrease in ovarian cancer risk. We call that an opportunistic salve in theectimy. So that I think nobody should have their tubes tied anymore, you know, in the general population or beer sacres, they should have their tubes removed if they're using that for their family planning and first control. The question becomes in beer sacres, how certain are we about this? Because again, ovarian cancer has no effective screening and Most women who are diagnosed with ovarian cancer are diagnosed at elite stage, and most women with a late stage ovarian cancer die of their disease. So this is where the challenge is. The studies are ongoing, but when will we feel strong enough to recommend that as a routine care when we know how bad ovarian cancer is. Right now, again, we don't have data sufficient to tell people that they can avoid having their ovaries removed. So what we're seeing more and more of is that a b r C one Karen might have her twos removed at thirty five and then her ovaries removed at forty. For a br C two care, that's more like forty and forty five.
00:26:28
Speaker 1: When do you think that data is going to be mature five years, ten years, twenty years.
00:26:32
Speaker 3: Here's my worry that if people are getting their twos removed at thirty five and then they still get their ovaries removed at forty one, we won't have the data. People have to keep their ovaries in long enough for us to prove it works right sort of past forty five or even un till each fifty. And I think this is the tension I always have in the clinic I'm really a clinician. First, I'm taking care of my patients. I'm a bit of a researcher. Second, for my patients, I don't want her to keep her overrays in. But from a research perspective, and less enough people continue to keep their ovaries, we're not going to have the data. So I think it's going to be a little bit tricky, and it might be a little bit entirely.
00:27:15
Speaker 1: Once I found out that I was a Brocco one carrier, the decision to remove my uterus, ovaries and fallopian tubes for me was straightforward. I was older, I'd already had children and experienced menopause. For younger women, making the same choice means two things. First, no further chance to conceive, and second, entering menopause overnight. These are big decisions and surgery might not be the best course of action for everyone. When we come back from the break, we'll discuss other preventive strategies for women to lower their risk, and we'll talk about some groundbreaking new treatments on the horizon. More from my conversation with Darja Susan Domchek in just a moment. Welcome back to the show. I'm speaking with doctor Susan damchek All about genetic testing. Her work is at the forefront of cancer prevention, cutting edge strategies that seek to stop cancer in its earliest stages. But before we get to that, I wanted to ask doctor Domck about some newer methods for identifying genetic risk. Let's move into just the different types of genetic testing that are out there now in terms of polygenic risk scores and whole genome sequencing. Can you speak to these newer forms of genetic testing a little bit?
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Speaker 3: Sure, So let's start with polygenic risk scores. And but that is a single alteration in FUERCA one increases your risk of breast cancer by up to seventy percent. It increases your risk google veering cancer up to forty five percent. Polygenic risk scores look at small, little changes throughout your DNA. The challenges of polygenic risk scores are that they're very dependent on ethnicity, and so in the United States when people are often sort of ethnically diverse, we haven't really figured it all out yet. Okay, So moving on a whole genome. So what is that? So, just as a reminder, we have a certain number of genes over twenty thousand. But when we test for genetics astibility, what we usually do is focus on genes known to be associated with cancer. So that can be a twenty five gene panel or an eighty gene panel or something like that. There is an approach that you can take called whole xome sequencing, which just sequences the known genes, but it sequences all the nome genes. And then there's whole genome sequencing, which sequences the whole genome. If you do a whole xome sequencing, you will find stuff. Most of us have stuff. The question then becomes does that stuff matter? And it might seem obvious that that stuff should matter, right that if you find something that it obviously should matter. But it turns out that genetics is not that simple as we sometimes say. Genetics is not destiny. Just because you have an alteration in some finding doesn't mean that you're going to get that condition. And there are a lot of genes where the risks associated with those genetic mutations aren't very high. An example I'll give is something called SDHA alterations in that gene predispose you to certain types of rare tumors, but the risk of that happening if you have an SDHA mutation is less than five percent. So if we identify someone with that, generally speaking, we don't do anything about it unless there's a family history consistent with it. I'm only using that as an example to show how you can get into trouble with things like collexm and whole genome sequencing, which is we're going to find a lot of stuff, but we won't necessarily know exactly how to use it for that individual patient.
00:31:03
Speaker 1: Let's move into prevention strategies, right for the woman who's not ready for prophylactic surgery, undergoing some screening, birth control pills, even life style. What are the impact of these strategies for women who carry brocka wan and Brocketo mutation.
00:31:15
Speaker 3: I think lifestyle is you know, the effects in berca in one and two mutation carriers may be modest, just because the genetics stuff is driving a lot of the risk. Having said that, healthy weight, minimizing alcohol, regular exercise, not smoking, these are all excellent things to do for women. There's a lot of debate about what safe level of alcohol is, but there has been some suggestion that you know, up to three drinks a week. The risk is very very low, so that's lifestyle always a good thing to do. The data for medications such as tamoxifin, loxifen, and another drug called exemesting in terms of decreasing the risk of breast cancer is limited in beer CA carriers, although it does seem like there is an impact in terms of ovarian cancer risk reduction. Oral contraceptive pills do seem to decrease the risk of a virile cancer. They also do slightly increase the risk of breast cancer, so it's a risk benefit decision. People have endometriosis or terrible heavy bleeding or just really terrible cycles in general, and birth control pills are really helpful or they need birth control, and particularly in this day and age in the United States, it's really important that people have access to affective birth control. So the birth control discussion with the risk benefit profile just needs to be individualized, so no easy answers there. We're obviously really interested in other approaches, so this new era of getting people better options is super important.
00:32:42
Speaker 1: Screening strategies, so breast screening is pretty well established with MRI mammogram ultrasound ovarian cancer screening a mind filled anything that you're excited about.
00:32:53
Speaker 3: Oh, varian cancer screening, it's just so difficult. As you know, we've been through other blood tests in the distant past, overshore, overseek over one, and I don't even remember all the OVAs that came and went over the years that weren't good tests. You know, I think that these new multi cancer early detection tests are interesting but as yet unproven and ovarying cancer early detection. This is why, unfortunately everyone feels so strongly still about removal of the oversease. It's because we don't have this well established the issue of transnagal ultrasend. They really just don't work very well at all, and there's a lot of false positives associated with them because pre menopausal women have all sorts of cysts depending on the timing of their cycle. So you know, the guidelines have sort of been all over the map given the absence of data. But a common strategy is to start ovarian cancer screening sort of at the time you would start considering removal of the ovarias, so like thirty five for BARC one or forty for br C two, in which case a false positive that led you down to removal of the ovarias. I'm not saying is not so bad because it's we're still taling with the impact, but it's in the range that we would consider that. So I'm curious about your approach to it, but that's often the approach that we take in the absence of better data.
00:34:11
Speaker 1: I'm looking forward to research and development of new screening tools. I think that you know twenty five ultracent. We use them, employ them, but realize that they're limited. But as the best we can do. Have to be super careful though in terms of caution, interpretation of results, really really really careful. But I want to get into your really exciting work with cancer interception and cancer vaccines. You know, our family history is pancreas cancer. You can't take out you're pancreas, and screening for pancreas cancer is limited and not well proven. So talk to me about cancer interception and cancer prevention vaccines.
00:34:47
Speaker 3: Yeah. Sure, So this phrase cancer interception, what does it even mean anyway, It's a way to try to differentiate from prevention. You know, when we talk about prevention, if it's a little bit like you don't smoke because smoking causes those changes that lead to cancer. Right, So prevention is you don't smoke, so you don't even start those changes. Cancer interception, which was going by Loose Blackburn and no prize winning scientists. It's trying to target the earliest stages of cancer development. The cancer has just started, but you can't detect it yet, and so that's cancer interception. So the idea here is that we try to target those first cells that are turning into cancer in a beer C carrier, so maybe I've lost the second copy of beer C for instance. So when you think about potential strategies, one of those strategies could be immune interception. So we really have a better understanding over the last you know, fifteen plus years that the immune system is incredibly important in cancer in a way that would have been you know, laughed at twenty five years ago. But we know that we can use immune therapies to help treat cancer. So one of the strategies that we're trying is to develop a vaccine that might develop immune cells that find those earliest cancer cells. You know, they're surveying your body and then as soon as that cell develops, they they target it and kill it. So we recently completed a study where we did vaccinate healthy BRC carriers using something called the DNA plasmid vaccine. What we were vaccine two isn't specific to BRC carriers, but it's the idea that you could identify a group that's at a high enough risk to try this. So the vaccine was safe, and now we're waiting to get the imminology results and then figure out our next phase. So that's sort of one approach. Let's use the immune system, let's target different types of immune strategies. We are also looking at mRNA types of approaches to vaccines. I mean, I do not view vaccines as a dirty word here, but if you want to call it immune interception as opposed to vaccines, I'll take that as well. But there's other ways to think about interceptions. So let's talk about pancreatic cancer. Pancreatic cancer. The risk of pancreatic cancer's highest in br C two rather than BRC one mutation carres, although the risk is elevated in both, and as you said, pancreatic cancer is a tough cancer. We do offer screening with either a endoscopic ulture sound or abdominal MRI, but as you mentioned, you know, it is limited, but almost all pancreatic cancers develop something called k Wrass mutations. So we actually also have work being done in the pass Or center looking at whether or not k wrass inhibitors in mice can decrease the risk of developing pancreatic cancer. So those are some some of the ideas that we have. There's other work going on. Could we use short doses of apartment hit er, these drugs that we use in the advanced cancer setting and in high risk breast cancer setting, could we use those intermittently to if you will, weed the garden and take out all those weeds before they develop into something, right, intermittently getting rid of all of those pre cancerous cells. So more to come, but it's a really exciting area that we're working on.
00:38:03
Speaker 1: If listeners could take away one point from this conversation, what would you like it to be to.
00:38:09
Speaker 3: Be proactive about getting your family history taken seriously? I think that patients can be, if you will, a little put off and be like, oh, don't worry about that. That's not enough to get genetic testing. And the fact is is that most doctors out there learned about genetic testing in medical school, you know, fifteen or twenty years ago, and they're not entirely up to date. It's not their fault. There's too much to do. But there's a lot of resources out there, and you can self refer to a genetic counselor to get more information if you're not getting the answers that you want.
00:38:43
Speaker 1: Are there resources for our listeners actually in terms of where they can go to learn more about this.
00:38:49
Speaker 3: Yeah, we do at faster dot org so BA s ser dot org. We have a lot about why genetic testing can be helpful and have provided some resources, including any large comprehensive cancer center will have genetic counselors available. There are plenty of physicians, gecologists, and primary care directors who comfortable with this and do you do it? So asking your primary care doctor first can always make sense, But if your primary care doctor doesn't know a lot about it or it's not really offering it to you, don't stop there. There are lots of different ways to get this done.
00:39:29
Speaker 1: I had cancer and I had seen some of the best physicians in the country for treatment. None of them ever mentioned to me genetic testing. I am literally a geneticist, and I didn't think that this applied to me. If you have family members with breast ovarian, pancreatic, or prostate cancer, it's worth it to consider genetic testing, even if your doctor hasn't suggested it, Even if you've been tested in the past a ten years or so, I'd recommend thinking about testing again. Technology is getting better and better each day. We're aware of more cancer causing genes than we were a decade ago, and we have more tools to treat those specific diseases. Your health insurance may cover genetic testing if you fall into a high risk group, but if not, there are lots of alternative ways that you can get genetic information you need. Direct to consumer options like I did are quick and easy, but I would always recommend connecting with a genetic counselor to help interpret your results. If you are positive for genetic mutation, there are a multitude of preventative measures that you can take, from prophylactic surgeries to risk reducing drugs like tomoxifen or reluxaphene. Ultimately, you are responsible for your own health. You have to advocate for yourself, but you don't have to do it alone. There are amazing places like the beast Or Center that can help you navigate this, Organizations that have testing, genetic counseling, treatment options, and positive communities all in one place. Taking that first step could save your life or the life of someone you love. Coming up on the next episode of Decoding Women's Health, I speak with a world renowned expert in medical cannabis. You are not going to want to miss this one.
00:41:21
Speaker 4: The top three indications for medical cannabis use across the country are chronic pain, mood or anxiety, and sleep disruption. Not surprisingly, these are the three top conditions we hear about in individuals who are either perimenopausal or postmenopausal.
00:41:35
Speaker 1: Decoding Women's Health is a production of Pushkin Industries and the Atria Health and Research Institute. This episode was produced by Rebecca Lee Douglas. It was edited by Amy Gaines McQuaid, mastering by Sarah Buguer. Our associate producer is Sonia Gerwit, backchecking by doctor David Dodick. Our executive producer is Alexandra Garreton. Our theme song was composed by HANNS. Brown. Concept and creative development by Shavn O'Connor. A special thanks to Alan Tish David Saltzman, Sarah Nix, Eric Sandler, More Ratner, Amy Hagdorn, Owen Miller, Jordan McMillan, and Greta Cohne. If you have questions about women's health and midlife and want expert advice, leave us a voicemail at four FI five two oh one, three three eight five, or send us a message at Decoding Women's Health at pushkin dot FM. I'm doctor Elizabeth Pointer, and thanks for listening. Until next time,
Speaker 1: Pushkin.
00:00:24
Speaker 2: This show is not a substitute for professional medical advice, diagnosis, or treatment. It is for informational purposes. Please consult your healthcare professional with any medical questions.
00:00:37
Speaker 1: My mom was diagnosed with breast cancer in her fifties. Luckily, it wasn't complicated and she quickly went into remission. But this April, she was diagnosed with pancreatic cancer, one of the most lethal and hardest cancers to treat. It was devastating news. I assumed it wasn't a hereditary cancer. Most aren't, but some cancers can be caused by genetic mutations like the Brca one and Brca two genes, sometimes referred to as the Braca genes. These are genes that normally protect cells from damage, but when they don't work, cancerous skyrockets. Years ago, I was actually testing myself for Brocca mutations. I sent off blood work for genetic testing with a private company. I never got the results back, and I sort of forgot about it. That is until my mom's doctors tested her blood and found out that she carried a Broco one mutation. Her cancer had a genetic heritable element. I contacted the testing company that I had sent my blood work to years earlier, and I finally got those results. I was positive for a BRCA one mutation. Myself, I would have been livid. If I wasn't so scared. I'd already had my own battle with HPV related cancer in twenty twenty one, and as a pelvic surgeon, I know too well the realities of ovarian cancer. Within weeks, I had my ovaries and fallopian tubes removed. The wildest part. I have a PhD in genetics. I worked with some of the best vision icians and scientists in the world. I am an expert in ovarian cancer, yet this potentially fatal mutation when undetected in me for nearly sixty three years. I'm doctor Elizabeth Pointer. And this is Decoding Women's Health, a show from Pushkin Industries and the Atria Health Institute. This elevating the conversation about women's health in midlife and frankly challenging some of the status quote information out there.
00:02:40
Speaker 3: As a medical and cologist, I was really interested in breast cancer and I was seeing so many young women with breast cancer and a family history, so trying to help people not have to face these terrible situations that they found themselves in was really compelling to me. So it was really being able to see how devastating this can be in families and at the same time, how he doesn't have to be.
00:03:04
Speaker 1: That's doctor Susan Domchuk. She's the executive director of the Bachsor Center for Braka at the Universe Pennsylvania. She's an oncologist who specializes in research, treatment, and prevention of BRCA related cancers. I wanted to have her on the show to talk about the importance of knowing your family history, when you should get tested, who should get tested, and what to do if you, like me, discover you carry a BRACA mutation. I realize that this can be a really scary topic for people, but I hope you leave this conversation like I did, feeling empowered. There are so many ways we can be proactive about our health, and simply having more information can make a big impact. So what do women need to know about their family history? Is that three generations back? You know? Sometimes when I take a family history, people will say, Oh, my immediate family doesn't have any cancer, but I have some aunts and uncles that may have had cancer. So what do women need to know about their family history.
00:04:18
Speaker 3: So this is such an important point, is knowing your family history and knowing this in more detail than previously has been understood. It's important to know who had cancer at what ages, going back three generations, as we say, so looking at cousins and grandparents and more distant relatives is extremely important. The second thing is that it's not just breast cancer. For br SA one and ber C two, those stand for breast cancer one and breast cancer two because we're just not creative, so BRCA one and BRSA two. But when we speak about those two specific genes, which are the most common cause of reditary breast and ovarian cancer, the cancers that are seen are breast cancer, ovarian cancer, pancreatic cancer, and prostate cancer. So really having a complete understanding. In addition, as you're alluding to, people in past generations didn't necessarily talk about cancer, so finding out why Aunt Martha died at forty is really important even if the family didn't talk about it. So having an open conversation with your relatives about the family history. And by the way, genetics isn't just about BERC one and two. People die of colon cancer and they're in colon cancer susceptibility genes, there's early onset cardiovasclar issues. And finally, individuals who are Ashkenazi Jewish descent have a much higher chance of having a BRC one or two mutation. That risk is one in forty as opposed to one in two hundred in the general population. So knowing your ethnicity, knowing your family history are all really important.
00:06:00
Speaker 1: Let's tat a little bit about if a Broka wan or brock A two gene mutation is being passed down the father side of the family, it can be a little bit more challenging to look at, right because your father is not going to get ovarian cancer. He may get breast cancer, but it can make it a little bit more challenging to look at these family histories and interpret them. Can you just talk about that a little bit.
00:06:21
Speaker 3: In the past, people felt that it was only the mother's side that mattered, that it was only breast cancer that mattered when you were thinking about family history and the risk of having a genetic susceptibility. But none of that is true. You're really looking at both sides of the family. Fifty percent of all cancer genetic susceptibility genes. They will come from the dad, not the mom. If you line up every r C mutation carry in the world, half our men. And we can't emphasize this point enough since it's so often missed. So we can see families which are really male dominated in which there's a ton of early on set prostate cancer, and that is justice concerning. It's also important to recognize that family size matters. So if it's just your dad and he was an only child and his father was an only child, cancer susceptibility genes can be hidden in those types of families. I want to also emphasize, and this may be a different point, that we have lower and lower thresholds to do genetic testing all the time, so sometimes we get a little caught up in these issues of the exact family history that we meet for genetic testing. But really it's just a matter of knowing anything about your family history, including well, I have a tiny family on my dad's side and I am concerned about having a genetic susceptibility for whatever reason. We also recognize that not everybody knows their family history if they're adopted, or for instance, the Holocaust may have taken out an entire generation, so we have a much lower threshold for testing in those situations.
00:07:56
Speaker 1: When we talk about this generic genetic testing for cancer, what are we talking about in.
00:08:01
Speaker 3: The old days, if you will, you know, fifteen years ago, we would be testing for two genes, generally BARC one and br C two. But what we've learned since the nineties is that there are other genes that are also associated with breast cancer. One of those is pretty like beer, say one and two. It's called PALBI two. But there are some other genes, notably genes called CHECK two and ATM, which increase your risk of breast cancer only modestly. So with beer, say one and two, that lifetime risk is seventy percent, with check two it's about twenty to twenty five percent. So now when people get genetic testing, they are almost never tested for just two genes. They're tested for a panel of genes that will include not only beer say one and two, but other genes associated with breast cancer risk. There's colon cancer susceptibility genes as well. There's kidney cancer susceptibility genes. So in general, we send sort of a panel of genes that hits the most common cancers. The specific genes on those panels are looking for what we call a pathogenic variant otherwise and as a mutation in a gene that basically makes the protein not function and that's what increases the risk of cancer.
00:09:19
Speaker 1: And these genes that we're testing for are pretty much all what we call tumor suppressor genes.
00:09:22
Speaker 3: Correct. That's correct. So what we mean by that is that all of us are born with two copies of each gene and in general cancer sceptibility genes. Say, beer SA one is good. Beer C one actually helps ourselves repair a specific type of DNA damage called bubble strand and break. So BERSA one and ber C two are good for us. They help us. It's only when we lose them where you are at increased risk or cancer.
00:09:55
Speaker 1: I just want to pause for a moment here and walk you through this. These concepts can feel so overwhelming and frankly terrifying for women who are trying to better understand their family history and their own risk. So you might have been surprised to hear doctor Domchek say Brako one and Broko two are good for us. But she's right, Broca genes aren't cancer causing genes. They're cancer preventing genes. They're actually helpful. They protect us by fixing damaged DNA. Like doctor John Chuck said, we're all born with two copies of those genes. People with Brocca mutations have a broken copy of the gene. Most of the time, that one working copy is enough to keep you safe, but if something happens to damage or turn off that second working copy, then you don't have any protection. When working properly, these genes literally suppress tumors. You can imagine. It's almost like having security guards that keep cancer from getting in. Only when you lose both guards can cancer develop. Briefly, what can you tell us about the biology of inherited cancers. They're a little different. They present a little bit earlier, so people a little bit younger when they're diagnosed, and they may have a little bit of a better outcome to treatment. Correct.
00:11:11
Speaker 3: Yeah, it's a great point, and this is where not all genetic susceptibility is equal. BRSA one is different than Chuck two. And the reason I emphasize this is because when we lump it all together, patients can make decisions that may not make sense for them. So it's really important to get gene specific information. BRSA one and two related cancers generally do occur earlier. The median onset of the cancers is in the early forties. But you're right that these tumors for BARSA one and two do seem to be more sensitive to chemotherapy, and so specifically, an ovarian cancer outcome is better with ovarian cancer if you have a br SA one art mutation. In breast cancer, it's kind of complicated because of the different types of breast cancer, but in ovarian cancer that prognosis is clearly better if you have a BRSA one on mutation. So the reason people with cancer should be tested is because we have drugs available that we can give them that will make their cancer do better. Every single person with ovarian cancer needs to have testing. Every single person with pancreatic cancer, with metastatic prostate cancer. That's enough. We don't have to think for a minute about family history. Those are sufficient for people to get genetic testing for breast cancer. Absolutely, anyone under fifty and more recently sort of anyone under sixty five is a candidate for genetic testing, and anyone with a certain type of breast cancer called triple negative breast cancer should get genetic testing. We should not leave a single person in those categories behind. They should all get genetic testing. At big academic medical centers. We're doing better and better. We keep track of our metrics, and we're at over eighty percent in any of those, but across the country those numbers are terrible. For ovarian cancer, it's under fifty percent, and it's hard to imagine why that is, because it actually helps us make decisions about therapy. So if anyone out there that's listening, if you fall into any of those groups, or any of your family members DOE, you absolutely should get genic testing.
00:13:23
Speaker 1: Let's face it, getting a cancer diagnosis is devastating, but a better understanding of any underlying genetic cause can significantly improve treatment outcomes coming up. If genetic testing can save lives, why are we all getting it done? Decoding women's health will be right back. Welcome back to Decoding women's health. You might be surprised to learn, as I was, that even when genetic testing is offered, many people are slow to take it up. Doctor Susan Donchek has been engaged in some really important work around this.
00:14:11
Speaker 3: Increasingly, there's discussion about what we call population screening, which is offering everybody if you will be or s one and two testing. The complications with that is that it's not entirely clear how many people really want to do that right now, and also how we actually will get it done. We've done some studies to offer genetic testing to if you will, anyone who's of Ashkenazi Jewish descent. The uptake wasn't as much as we thought. We did a study a few years ago testing about four thousand individuals in that situation, and they didn't have to have any family history. We thought it would take about three months to test four thousand people in for cities, and it took us three years. And other data have really suggested that it matters if your doctor recommends this to you. And this is why this is so important to get out. We need to educate patients people out there in the community about the potential risk, and we also need to educate for to have a really low threshold to do genetic testing if there's a family history or again if people are of Ashkenazi Jewish to sent we're just going to the electronic health record and pulling out individuals who've told their providers that they have a family history and sending them messages saying you should consider getting genetic testing. And just in our preliminary data, just that simple effort, twenty five percent of people schedule appointments to get genetic testing. So people are interested, they just don't know about it. I think that we can use simple solutions of asking people at the right time and then immediately referring them to genetics. Our primary care doctors have a lot to do, so this idea that we can expect them to also do a great screening for these things and get people tested. It might happen, but it's a lot we need to help our primary care doctors.
00:16:05
Speaker 1: About what age did you start to consider genetic testing? Twenty two to twenty five.
00:16:10
Speaker 3: There's really two reasons to test. The first reason is because you're going to change your medical decision making, and for most cancer susceptibility genes, you know, we don't start doing anything different medically until age twenty five. That's when we start. For instance, restmeris for BERC one mutation cares. Now, there are sometimes where there's a particularly early onset in the family where we would potentially do it earlier, but in general, we have twenty five in our heads. There's another reason to get genetic testing for BRSA one two and other cancer sceptibility genes, and that's for reproductive decision making, and that takes on two different pieces. One pre implantation genetic testing, So this is when individuals go through in vitro fertilization, screen the embryos and only reimplant the embryos that don't have the BRC one or BRC two mutation. Well, some people are not interested in this, but this technology is available. So there are times that you know, women are interested in starting their families before their twenty five So that's another reason to consider screening. In addition, several of the genes that we're talking about, and I'll give br C two as an example. In rare situations, a baby can inherit two bad copies of ber C two, one from each parent, and when that occurs, there's a twenty five percent chance that the baby will have a condition called fincnianemia, which is a serious medical condition. So these are all reasons to consider genetic testing sort of at the time you're starting to think about your family or medical decision making, and so that matters for the men too, because in general, we don't really start much for men in terms of their personal screening until closer to forty, but when they're ready to start having their children. If one of their parents has a BERC mutation, then we certainly talk about screening before they start having their kids. So I think it's really important that people know that even if their doctor doesn't bring it up, that it still may be real to them, and that they can either talk to their doctors about it they're gynecologists, a primary care doctor, or see a genetic counselor for testing. There are also direct to consumer approaches to genetic testing, where people can just go online and order the tests themselves. There are pros and cons to those approaches, but right now you know it's all hands on deck. There are multiple ways to get this testing done, and we should make sure that people know about all of them.
00:18:41
Speaker 1: I took the direct to consumer route myself. There are plenty of companies that offer easy to use at home testing kits that you can just mail in and get the results online. The benefit is that it's quick, easy, and relatively inexpensive. The problem is is that you don't have guidance and support necessarily that comes with getting tested with a personal physician. So if you go this route, I strongly advise connecting with the genetic counselor beforehand. Even if you think that you're prepared to learn that you carry a genetic mutation, actually getting that result can still pack a huge emotional punch. Having an expert in your corner helps you understand what the result means and what steps to take next. The National Society of Genetic Counselors has a registry where you can find professionals to guide you. Having said that, in an ideal world, everyone would be guided through genetic testing in person by a physician they trust, but one of the barriers to this sort of testing for many patients is cost. In some cases, patients can get the testing paid for by their insurance. The National Comprehensive Cancer Network provides guidelines for testing that include the big factors that we've discussed today, If you're of Ashkenizi Jewish descent, if you've had blood relatives with a confirmed cancer causing gene variant, or if you or a family member has a personal history of a rare or multiple cancers. I asked doctor Domchek, what about patients are women who don't fall into these categories.
00:20:13
Speaker 3: If people don't meet those guidelines at most labs, there are still self pay options that cost about three hundred dollars. But I will say that navigating this can sometimes be frustrating and complex for patients. So I think that when people meet clear criteria for JANK testing, everything goes through very well. If people are more on the bubble, self pay options are actually going to be cheaper than if you will going through insurance where it may not be covered at.
00:20:42
Speaker 1: All, for people who may not be able to afford the three hundred dollars. Are you aware of any support services for these individuals?
00:20:49
Speaker 3: Yes, there are, and oftentimes the labs have held there are various programs that exist. It does get a little bit complicated if people do not have insurance at all. It can be tricky because even if we could get someone free testing, we're not able to then get them the medical care that they need. So that is a big gap right now. Is people who are completely uninsured. We really do struggle because even if we could test them, we would not really be able to care for them, and that doesn't feel great. So hopefully all insurance problems in the United States will be fixed and we won't have to worry about it. But I'm not going to hold my breath right now for that.
00:21:30
Speaker 1: So a lot of upside to genetic testing allowing you to do some planning, and we'll move into that in just a moment.
00:21:36
Speaker 3: Any downsides, Sure, this is information that can be extremely difficult to learn. I had a physician once tell me she felt that the genetic testing both saved your life had ruined it. And she didn't really mean ruin it, but she just at dealing with this information making the decisions she had to make well really difficult. And so, first of all, we always like to emphasize that when you get your genetic test result back, if it's positive, that was always there. You were positive from the time you were born. You know, you didn't change on a dime day to day. We also like to talk about lifetime risks. So when we talk about lifetime risk of cancer as highly seventy percent, that's not your risk tomorrow, that's your risk over your whole life. But you can imagine that feeling getting that information is really overwhelming, and so our job is to try to counsel people through it. To focus on the immediate next steps of what needs to happen. Currently, the only effective strategy for a varying cancer risk reduction is early surgery, so premenopausal to me removable of your ovaries before you or otherwise we go into menopause, and that has significant issues for women. We try to get people through it as best we can, but it's still fun to have to consider these things and then deciding whether to continue to screen or do astectomy. That can be challenging for parents to get tested. We see a lot that when individuals get tested that have children, they can feel very sad and sometimes guilty about the potential that they've passed this belong to their children. Of course, we all pass along good and bad genes to our kids. In this case, you just kind of know what it is. But these are real issues that we know that people struggle with, and our job is to try to help people through this time and really focus on the fact that this information can be life saving, but at the same time acknowledge the grief that's involved in having to make these decisions.
00:23:33
Speaker 1: So I'm diagnosed with the bracket one mutation in twenty twenty five, what does taking action look like as a younger woman, as a primin apausal woman.
00:23:42
Speaker 3: Yes, and so in twenty twenty five, there are clear things that women can do, but we are actively hoping for better options. So right now, at twenty five, all someone needs to do is get a breast MRI once a year. The risk of developing breast cancer prior to age thirty when you're a twenty five year old beer C one mutation carries less than five percent, but that's still much higher than an average woman. So brust emri once a year. At thirty, we have to mammogram, so that every six months you're getting an MRI or a mammogram. Unfortunately, between age thirty five and forty women should undergo remove all the pilopian tubes and ovaries. So this is for bars one now. Risk reducing mass tec to me or prophylactic masks tec to me can be done at any time with an individual with a br c in one or two or other gene mutations. Some women are not interested in mask tec tomy at all and will continue screening, so we like to have an honest conversation about their goals about body image, about sexuality, and other quality of life issues as people make their decisions.
00:24:50
Speaker 1: What about just removal of the pelopian tubes alone, without removing the ovaries. Is that data mature enough for us to make that recommendation now?
00:24:57
Speaker 3: Not? Yeah, but boy, I want it to be.
00:24:59
Speaker 1: So.
00:25:00
Speaker 3: The theory behind this, as you're alluding to, is that there's data that many ovarian cancers arise in the philopian tube and that potentially if we just remove the philippian tubes, we can decrease the risk of ovarian cancer. And there's some interesting sort of data out there, including a study that's being done in British Columbia where every woman who's coming in to have her tubes tied just has their tubes removed, and again the very early data suggests that there's a decrease in ovarian cancer risk. We call that an opportunistic salve in theectimy. So that I think nobody should have their tubes tied anymore, you know, in the general population or beer sacres, they should have their tubes removed if they're using that for their family planning and first control. The question becomes in beer sacres, how certain are we about this? Because again, ovarian cancer has no effective screening and Most women who are diagnosed with ovarian cancer are diagnosed at elite stage, and most women with a late stage ovarian cancer die of their disease. So this is where the challenge is. The studies are ongoing, but when will we feel strong enough to recommend that as a routine care when we know how bad ovarian cancer is. Right now, again, we don't have data sufficient to tell people that they can avoid having their ovaries removed. So what we're seeing more and more of is that a b r C one Karen might have her twos removed at thirty five and then her ovaries removed at forty. For a br C two care, that's more like forty and forty five.
00:26:28
Speaker 1: When do you think that data is going to be mature five years, ten years, twenty years.
00:26:32
Speaker 3: Here's my worry that if people are getting their twos removed at thirty five and then they still get their ovaries removed at forty one, we won't have the data. People have to keep their ovaries in long enough for us to prove it works right sort of past forty five or even un till each fifty. And I think this is the tension I always have in the clinic I'm really a clinician. First, I'm taking care of my patients. I'm a bit of a researcher. Second, for my patients, I don't want her to keep her overrays in. But from a research perspective, and less enough people continue to keep their ovaries, we're not going to have the data. So I think it's going to be a little bit tricky, and it might be a little bit entirely.
00:27:15
Speaker 1: Once I found out that I was a Brocco one carrier, the decision to remove my uterus, ovaries and fallopian tubes for me was straightforward. I was older, I'd already had children and experienced menopause. For younger women, making the same choice means two things. First, no further chance to conceive, and second, entering menopause overnight. These are big decisions and surgery might not be the best course of action for everyone. When we come back from the break, we'll discuss other preventive strategies for women to lower their risk, and we'll talk about some groundbreaking new treatments on the horizon. More from my conversation with Darja Susan Domchek in just a moment. Welcome back to the show. I'm speaking with doctor Susan damchek All about genetic testing. Her work is at the forefront of cancer prevention, cutting edge strategies that seek to stop cancer in its earliest stages. But before we get to that, I wanted to ask doctor Domck about some newer methods for identifying genetic risk. Let's move into just the different types of genetic testing that are out there now in terms of polygenic risk scores and whole genome sequencing. Can you speak to these newer forms of genetic testing a little bit?
00:28:42
Speaker 3: Sure, So let's start with polygenic risk scores. And but that is a single alteration in FUERCA one increases your risk of breast cancer by up to seventy percent. It increases your risk google veering cancer up to forty five percent. Polygenic risk scores look at small, little changes throughout your DNA. The challenges of polygenic risk scores are that they're very dependent on ethnicity, and so in the United States when people are often sort of ethnically diverse, we haven't really figured it all out yet. Okay, So moving on a whole genome. So what is that? So, just as a reminder, we have a certain number of genes over twenty thousand. But when we test for genetics astibility, what we usually do is focus on genes known to be associated with cancer. So that can be a twenty five gene panel or an eighty gene panel or something like that. There is an approach that you can take called whole xome sequencing, which just sequences the known genes, but it sequences all the nome genes. And then there's whole genome sequencing, which sequences the whole genome. If you do a whole xome sequencing, you will find stuff. Most of us have stuff. The question then becomes does that stuff matter? And it might seem obvious that that stuff should matter, right that if you find something that it obviously should matter. But it turns out that genetics is not that simple as we sometimes say. Genetics is not destiny. Just because you have an alteration in some finding doesn't mean that you're going to get that condition. And there are a lot of genes where the risks associated with those genetic mutations aren't very high. An example I'll give is something called SDHA alterations in that gene predispose you to certain types of rare tumors, but the risk of that happening if you have an SDHA mutation is less than five percent. So if we identify someone with that, generally speaking, we don't do anything about it unless there's a family history consistent with it. I'm only using that as an example to show how you can get into trouble with things like collexm and whole genome sequencing, which is we're going to find a lot of stuff, but we won't necessarily know exactly how to use it for that individual patient.
00:31:03
Speaker 1: Let's move into prevention strategies, right for the woman who's not ready for prophylactic surgery, undergoing some screening, birth control pills, even life style. What are the impact of these strategies for women who carry brocka wan and Brocketo mutation.
00:31:15
Speaker 3: I think lifestyle is you know, the effects in berca in one and two mutation carriers may be modest, just because the genetics stuff is driving a lot of the risk. Having said that, healthy weight, minimizing alcohol, regular exercise, not smoking, these are all excellent things to do for women. There's a lot of debate about what safe level of alcohol is, but there has been some suggestion that you know, up to three drinks a week. The risk is very very low, so that's lifestyle always a good thing to do. The data for medications such as tamoxifin, loxifen, and another drug called exemesting in terms of decreasing the risk of breast cancer is limited in beer CA carriers, although it does seem like there is an impact in terms of ovarian cancer risk reduction. Oral contraceptive pills do seem to decrease the risk of a virile cancer. They also do slightly increase the risk of breast cancer, so it's a risk benefit decision. People have endometriosis or terrible heavy bleeding or just really terrible cycles in general, and birth control pills are really helpful or they need birth control, and particularly in this day and age in the United States, it's really important that people have access to affective birth control. So the birth control discussion with the risk benefit profile just needs to be individualized, so no easy answers there. We're obviously really interested in other approaches, so this new era of getting people better options is super important.
00:32:42
Speaker 1: Screening strategies, so breast screening is pretty well established with MRI mammogram ultrasound ovarian cancer screening a mind filled anything that you're excited about.
00:32:53
Speaker 3: Oh, varian cancer screening, it's just so difficult. As you know, we've been through other blood tests in the distant past, overshore, overseek over one, and I don't even remember all the OVAs that came and went over the years that weren't good tests. You know, I think that these new multi cancer early detection tests are interesting but as yet unproven and ovarying cancer early detection. This is why, unfortunately everyone feels so strongly still about removal of the oversease. It's because we don't have this well established the issue of transnagal ultrasend. They really just don't work very well at all, and there's a lot of false positives associated with them because pre menopausal women have all sorts of cysts depending on the timing of their cycle. So you know, the guidelines have sort of been all over the map given the absence of data. But a common strategy is to start ovarian cancer screening sort of at the time you would start considering removal of the ovarias, so like thirty five for BARC one or forty for br C two, in which case a false positive that led you down to removal of the ovarias. I'm not saying is not so bad because it's we're still taling with the impact, but it's in the range that we would consider that. So I'm curious about your approach to it, but that's often the approach that we take in the absence of better data.
00:34:11
Speaker 1: I'm looking forward to research and development of new screening tools. I think that you know twenty five ultracent. We use them, employ them, but realize that they're limited. But as the best we can do. Have to be super careful though in terms of caution, interpretation of results, really really really careful. But I want to get into your really exciting work with cancer interception and cancer vaccines. You know, our family history is pancreas cancer. You can't take out you're pancreas, and screening for pancreas cancer is limited and not well proven. So talk to me about cancer interception and cancer prevention vaccines.
00:34:47
Speaker 3: Yeah. Sure, So this phrase cancer interception, what does it even mean anyway, It's a way to try to differentiate from prevention. You know, when we talk about prevention, if it's a little bit like you don't smoke because smoking causes those changes that lead to cancer. Right, So prevention is you don't smoke, so you don't even start those changes. Cancer interception, which was going by Loose Blackburn and no prize winning scientists. It's trying to target the earliest stages of cancer development. The cancer has just started, but you can't detect it yet, and so that's cancer interception. So the idea here is that we try to target those first cells that are turning into cancer in a beer C carrier, so maybe I've lost the second copy of beer C for instance. So when you think about potential strategies, one of those strategies could be immune interception. So we really have a better understanding over the last you know, fifteen plus years that the immune system is incredibly important in cancer in a way that would have been you know, laughed at twenty five years ago. But we know that we can use immune therapies to help treat cancer. So one of the strategies that we're trying is to develop a vaccine that might develop immune cells that find those earliest cancer cells. You know, they're surveying your body and then as soon as that cell develops, they they target it and kill it. So we recently completed a study where we did vaccinate healthy BRC carriers using something called the DNA plasmid vaccine. What we were vaccine two isn't specific to BRC carriers, but it's the idea that you could identify a group that's at a high enough risk to try this. So the vaccine was safe, and now we're waiting to get the imminology results and then figure out our next phase. So that's sort of one approach. Let's use the immune system, let's target different types of immune strategies. We are also looking at mRNA types of approaches to vaccines. I mean, I do not view vaccines as a dirty word here, but if you want to call it immune interception as opposed to vaccines, I'll take that as well. But there's other ways to think about interceptions. So let's talk about pancreatic cancer. Pancreatic cancer. The risk of pancreatic cancer's highest in br C two rather than BRC one mutation carres, although the risk is elevated in both, and as you said, pancreatic cancer is a tough cancer. We do offer screening with either a endoscopic ulture sound or abdominal MRI, but as you mentioned, you know, it is limited, but almost all pancreatic cancers develop something called k Wrass mutations. So we actually also have work being done in the pass Or center looking at whether or not k wrass inhibitors in mice can decrease the risk of developing pancreatic cancer. So those are some some of the ideas that we have. There's other work going on. Could we use short doses of apartment hit er, these drugs that we use in the advanced cancer setting and in high risk breast cancer setting, could we use those intermittently to if you will, weed the garden and take out all those weeds before they develop into something, right, intermittently getting rid of all of those pre cancerous cells. So more to come, but it's a really exciting area that we're working on.
00:38:03
Speaker 1: If listeners could take away one point from this conversation, what would you like it to be to.
00:38:09
Speaker 3: Be proactive about getting your family history taken seriously? I think that patients can be, if you will, a little put off and be like, oh, don't worry about that. That's not enough to get genetic testing. And the fact is is that most doctors out there learned about genetic testing in medical school, you know, fifteen or twenty years ago, and they're not entirely up to date. It's not their fault. There's too much to do. But there's a lot of resources out there, and you can self refer to a genetic counselor to get more information if you're not getting the answers that you want.
00:38:43
Speaker 1: Are there resources for our listeners actually in terms of where they can go to learn more about this.
00:38:49
Speaker 3: Yeah, we do at faster dot org so BA s ser dot org. We have a lot about why genetic testing can be helpful and have provided some resources, including any large comprehensive cancer center will have genetic counselors available. There are plenty of physicians, gecologists, and primary care directors who comfortable with this and do you do it? So asking your primary care doctor first can always make sense, But if your primary care doctor doesn't know a lot about it or it's not really offering it to you, don't stop there. There are lots of different ways to get this done.
00:39:29
Speaker 1: I had cancer and I had seen some of the best physicians in the country for treatment. None of them ever mentioned to me genetic testing. I am literally a geneticist, and I didn't think that this applied to me. If you have family members with breast ovarian, pancreatic, or prostate cancer, it's worth it to consider genetic testing, even if your doctor hasn't suggested it, Even if you've been tested in the past a ten years or so, I'd recommend thinking about testing again. Technology is getting better and better each day. We're aware of more cancer causing genes than we were a decade ago, and we have more tools to treat those specific diseases. Your health insurance may cover genetic testing if you fall into a high risk group, but if not, there are lots of alternative ways that you can get genetic information you need. Direct to consumer options like I did are quick and easy, but I would always recommend connecting with a genetic counselor to help interpret your results. If you are positive for genetic mutation, there are a multitude of preventative measures that you can take, from prophylactic surgeries to risk reducing drugs like tomoxifen or reluxaphene. Ultimately, you are responsible for your own health. You have to advocate for yourself, but you don't have to do it alone. There are amazing places like the beast Or Center that can help you navigate this, Organizations that have testing, genetic counseling, treatment options, and positive communities all in one place. Taking that first step could save your life or the life of someone you love. Coming up on the next episode of Decoding Women's Health, I speak with a world renowned expert in medical cannabis. You are not going to want to miss this one.
00:41:21
Speaker 4: The top three indications for medical cannabis use across the country are chronic pain, mood or anxiety, and sleep disruption. Not surprisingly, these are the three top conditions we hear about in individuals who are either perimenopausal or postmenopausal.
00:41:35
Speaker 1: Decoding Women's Health is a production of Pushkin Industries and the Atria Health and Research Institute. This episode was produced by Rebecca Lee Douglas. It was edited by Amy Gaines McQuaid, mastering by Sarah Buguer. Our associate producer is Sonia Gerwit, backchecking by doctor David Dodick. Our executive producer is Alexandra Garreton. Our theme song was composed by HANNS. Brown. Concept and creative development by Shavn O'Connor. A special thanks to Alan Tish David Saltzman, Sarah Nix, Eric Sandler, More Ratner, Amy Hagdorn, Owen Miller, Jordan McMillan, and Greta Cohne. If you have questions about women's health and midlife and want expert advice, leave us a voicemail at four FI five two oh one, three three eight five, or send us a message at Decoding Women's Health at pushkin dot FM. I'm doctor Elizabeth Pointer, and thanks for listening. Until next time,
