How family history affects cancer genetics innovation [Music playing] [Text on screen: The James The Ohio State University Comprehensive Cancer Center Cancer-Free World Podcast cancer.osu.edu] Leigha Senter, MS, CGC: Somebody is always the first one to test positive. Steve Wartenberg: Right. [Text on screen: Leigha Senter, MS, CGC Licensed Genetic Counselor OSUCCC - James] Leigha Senter, MS, CGC: And then our next step is to tell that person that they need to share all of this information that we just gave them with as many family members as possible. Because it's that cascade of events. Actually, we call it cascade testing then, is where our real potential is to keep people from getting cancer. Steve Wartenberg: This is The James Cancer-Free World Podcast. I'm Steve Wartenberg, and my guest is Leigha Senter. [Text on screen: Steve Wartenberg Host The James Cancer-Free World Podcast] [Music fades] Steve Wartenberg: Leigha is a James licensed genetic counselor who specializes in hereditary gynecological cancers and something that's called cascade testing in families with hereditary cancer syndromes. Genetic testing and counseling saves lives, and The James has one of the largest and best programs anywhere. Welcome to the podcast, Leigha. Leigha Senter, MS, CGC: Thanks for having me. I'm happy to be here. Steve Wartenberg: This is a really interesting and important topic, so I'm ready to get going. And I thought we would start with something kind of basic, but not quite as simple as it sounds, and that's kind of what are genetic mutations and how do they cause cancer? [Text on screen: Leigha Senter, MS, CGC Licensed Genetic Counselor OSUCCC - James] Leigha Senter, MS, CGC: Yeah, that's a great question. There are thousands and thousands of genes inside every single cell of your body, and we know that a certain class of them actually are working all of the time to help protect us against cancer. So that's their job. And you can imagine if you had some of those genes or one of those genes not working properly, that means the protection isn't happening at the level that you would want it to. Steve Wartenberg: Are you talking about the immune system? Leigha Senter, MS, CGC: Not necessarily, no. Steve Wartenberg: Oh, okay. Leigha Senter, MS, CGC: Not the immune system. So these genes generally are involved in telling your cells when it's time to stop growing, and we all acquire mutations over the course of our lifetime, just the natural process of aging really. But in cancer genetics, we're focused on those rare instances where a person can be born with a mutation. It's kind of like a glitch in one of these cancer protector genes that's increasing that person's chance of developing cancer over their lifetime. Steve Wartenberg: Now, if a person is born with a mutation, is that always, or sometimes from an inherited genetic mutation? [Text on screen: Leigha Senter, MS, CGC Licensed Genetic Counselor OSUCCC - James] Leigha Senter, MS, CGC: Generally, yes. So these kinds of mutations that are inherited are usually passed through families, from parents to children. And those mutations don't guarantee that a person is absolutely going to get cancer in their lifetime, but compared to the average person, it makes the chance much greater. Steve Wartenberg: Okay. So there's inherited genetic mutations, but there's also ones that are acquired through smoking, too much exposure to the sun, right? Leigha Senter, MS, CGC: Yes. Steve Wartenberg: Those are not inherited. So there's no way to know if a person has that cancer until they have that cancer. Leigha Senter, MS, CGC: That's right. And the other distinction is that those kinds of mutations that we acquire over our lifetime aren't passed on to our children. Steve Wartenberg: Right. Yeah. That's important. So when you say passed on, how does that work? Just to make it easier, a husband and wife, the mother has an inherited genetic mutation. What happens when she has children? [Text on screen: Leigha Senter, MS, CGC Licensed Genetic Counselor OSUCCC - James] Leigha Senter, MS, CGC: Yeah, so each of these mutations, for the most part in cancer genetics, there are some exceptions, but most of them are what we call dominant, meaning that you can have one mutation in one gene, and that gives you the increased risk. And so in your example, any child of that pair would have a 50-50 chance of also having that same genetic mutation and as a result, those same increased cancer risks. Steve Wartenberg: Each child would have a 50-50 risk. Leigha Senter, MS, CGC: Each child. Steve Wartenberg: And is it the same if it's the father? Leigha Senter, MS, CGC: That's correct. Yep. You can inherit these from either parent. Steve Wartenberg: And then each child, if the first child does not have the inherited genetic mutation, are their children safe? [Text on screen: Leigha Senter, MS, CGC Licensed Genetic Counselor OSUCCC - James] Leigha Senter, MS, CGC: If you don't have it, you can't have passed it on. So it does stop when there's something truly inherited in the family. Some people take the 50-50 risk of inheriting one of these mutations to assume that that means if they have two children, one will have it and one won't, the one in two. But it really is an independent 50% chance for every single child. Steve Wartenberg: So that's when we get into the importance of genetic testing and family history. So let's talk about that family history, because every time you go to the doctor, they always ask for your family history, and it's actually very, very important to know and give your family history to your primary care physician. Leigha Senter, MS, CGC: It is. And family histories are dynamic. They change over time. So if you feel like you're answering the same questions every time you go to the doctor, that's a good thing because at some point the answers to those questions are going to change. Steve Wartenberg: Not sure if your parent has an incident the next time you see the doctor, you might want to put that in there. [Text on screen: Leigha Senter, MS, CGC Licensed Genetic Counselor OSUCCC - James] Leigha Senter, MS, CGC: That's right. That's right. And when we think about family history and cancer genetics, sometimes we're thinking about a broader spectrum of relatives though. Sometimes people may ask about your siblings and parents, and those are very important obviously. But it matters if your grandparents or your aunts or uncles, even your cousins have been diagnosed with cancer. And all of that information really can inform how likely it is that your family has a hereditary predisposition to cancer. Steve Wartenberg: So give us sort of an example of a patient or two you've seen that had the type of family history that would make their primary care physician say, "Hey, you need to go see Leigha and get a genetic screening and counseling." [Text on screen: Leigha Senter, MS, CGC Licensed Genetic Counselor OSUCCC - James] Leigha Senter, MS, CGC: Yeah. I think the primary care community relies a lot on the published criteria that tell them, if you see a patient and they see this in their family history, they should be referred. But some of the common reasons that might raise a red flag are having a person in your family who was diagnosed with a cancer at a younger than expected age. That can raise a red flag from a hereditary standpoint. Or you're seeing a pattern of cancers in the family that we know can be linked together in a hereditary way. So sometimes we know breast and ovarian cancers are inherited in a similar fashion. And so whenever your provider notices that in your family history, or if you're a patient and you notice that in your own family history, you should probably ask about seeing someone in cancer genetics. But the tricky part of all of this is we have all of these red flags to pay attention for, but sometimes we don't see the red flags and a person ends up with a hereditary predisposition. So if you have anyone in your family, just a single person with ovarian cancer or a single person in your family with pancreatic cancer, we know that those are sometimes associated with hereditary syndromes more commonly than some other cancer types. And that's all it would take. So we're not seeing 30 people in the same family with the same kind of cancer. It doesn't need to be that extreme, but knowing your family history definitely makes a difference. Steve Wartenberg: But it also can be fairly extreme. Maybe not 30 people, but it could be a mother, daughter, grandmother, could all have had breast cancer at an earlier than expected age, and that's really a red flag, right? Or colorectal cancer the same way. Leigha Senter, MS, CGC: Yes. That's right. Steve Wartenberg: So actually, that at least to me brings up a question is what are some of the most common inherited genetic mutations and what do they cause? [Text on screen: Leigha Senter, MS, CGC Licensed Genetic Counselor OSUCCC - James] Leigha Senter, MS, CGC: One of the most common hereditary cancer syndromes is associated with mutations that you can inherit in one of two genes, BRCA1 or BRCA2. And sometimes people pronounce those BRCA. Steve Wartenberg: Right. But I've learned that geneticists don't like that. Leigha Senter, MS, CGC: That's true. Steve Wartenberg: You like to say the whole. Leigha Senter, MS, CGC: We do. Yeah. Steve Wartenberg: What does it stand for? Leigha Senter, MS, CGC: Yeah. BR stands for breast and CA is cancer. Steve Wartenberg: So it's an inherited breast cancer genetic mutation. Leigha Senter, MS, CGC: It is. Steve Wartenberg: And there's two types. Leigha Senter, MS, CGC: Right. So there are two separate genes. And a single mutation in either of those genes does in fact increase the risk for breast cancer in females and potentially males. But what we've grown to learn over the years are those same two genes are also the most common cause of hereditary ovarian cancer, hereditary pancreatic cancer, and hereditary prostate cancer. And so when we think about it now, if we had known all of this many, many years ago, those genes may have a different name because they're not just associated with breast cancer risk. Steve Wartenberg: Oh, I hadn't thought of that. Initially they detected it in breast cancer patients, but if they had detected it in prostate cancer, it could have a whole different name. And that name probably prevented some people from being as aware of it as they should have been. [Text on screen: Leigha Senter, MS, CGC Licensed Genetic Counselor OSUCCC - James] Leigha Senter, MS, CGC: Right. And I feel like if anybody's talking about these genes, it's a good thing. But we really do have to keep reminding people, these are not exclusively breast cancer genes. They are very important for families and patients with lots of different kinds of cancer. Steve Wartenberg: So if, and this might get a little complicated, but if a woman has one of the two BRCA genes, how much does that increase her risk of breast cancer or other types of cancer? Leigha Senter, MS, CGC: It does increase it significantly. So most females have about a 12% chance or so over the course of their lifetime to develop breast cancer, give or take. With one of these mutations, depending on the study that you read, that risk can be anywhere from 50 to 80%. Steve Wartenberg: Wow. More than half. Leigha Senter, MS, CGC: Yeah. Yeah. So obviously when we identify that in a person, if they've not had cancer, we need to make their screening plan match that higher level of risk and not just subscribe to the average risk recommendations. Steve Wartenberg: And now obviously you would want to do more mammograms or other kind of breast imaging more frequently, but because it causes other types of cancer, how do you screen for that as well? [Text on screen: Leigha Senter, MS, CGC Licensed Genetic Counselor OSUCCC - James] Leigha Senter, MS, CGC: Right. So this is partly where the family history is so important. But when a person has a BRCA mutation, we absolutely start breast imaging younger and do it more intensely with breast MRI in addition to mammogram. But ovarian cancer is very difficult to screen for. And in that situation, we actually do recommend removal of the ovaries and fallopian tubes. The timing is different for every person who tests positive. But with pancreatic cancer screening, it's not something that's available just everywhere. But if you have a BRCA mutation and a family history of pancreatic cancer, we do actually recommend meeting with a specialist for consideration of pancreatic surveillance. We are very lucky to have someone who offers that here at The James. And so we refer a lot of our patients for that discussion. Steve Wartenberg: And men can get the BRCA as well. Leigha Senter, MS, CGC: That's right. Steve Wartenberg: And pass it on. So that's important to know. I don't want to put words in your mouth, but is that the most common genetic mutation you see, or just one of them? Leigha Senter, MS, CGC: It's one of the most common, I think. Steve Wartenberg: So what would be another one? [Text on screen: Leigha Senter, MS, CGC Licensed Genetic Counselor OSUCCC - James] Leigha Senter, MS, CGC: Lynch syndrome is another one that's probably similarly as prevalent in people. And Lynch syndrome is caused by mutations in a different set of genes. So not the BRCA genes, but there are a handful of other genes that can cause Lynch syndrome. And when you have inherited a mutation in one of those genes, it increases risk primarily for colon cancer and endometrial or uterine cancer. But then there are other cancers that we can see at an increased frequency too. Steve Wartenberg: Now, I've learned from you and others that the amazing thing about detecting someone with Lynch syndrome is you can find pre-cancerous polyps and prevent the person from ever getting cancer. So how do you make that happen when you figure out a family has Lynch syndrome and begin your testing? Leigha Senter, MS, CGC: That's exactly right. It's one of the very few screening tools that we have at our disposal that can keep a cancer from happening rather than detect it at an early stage, which is also important. But a lot of people don't love us telling them that they need to have colonoscopies starting at a younger age and doing it more frequently. But it's so important when a family has Lynch syndrome and really is life-changing for the family if they're able to get their colonoscopies. Steve Wartenberg: Well, I would add life-saving. Leigha Senter, MS, CGC: Yeah, you're right. Steve Wartenberg: And that means that someone now, you're supposed to start at 45, but if you have Lynch syndrome, you would start your testing at... Leigha Senter, MS, CGC: Potentially as early as age 25. Or if you happen to have a family history where people were getting cancer even younger than that, we would start younger based on your family history. Some forms of Lynch syndrome don't usually present as young. And so in those families, we'll adjust the age to 30. But the idea is we're using the genetic test results to make a personalized plan for the family. Steve Wartenberg: Making a personalized plan through genetic testing is key. Is there another inherited genetic mutation or two do you want to just briefly mention? We don't have to get into as much detail because I know that there's a lot. [Text on screen: Leigha Senter, MS, CGC Licensed Genetic Counselor OSUCCC - James] Leigha Senter, MS, CGC: There are a lot. We used to just test for one or two of these things at a time. We would see a family and just test them for the BRCA mutations. But we know that those genes are not the only ones that are playing a role in our cancer risk. And so over the last 10 years or so, the discoveries have really come rapidly. And it's pretty typical when we see a patient in cancer genetics now that we're ordering a test that includes 30 genes, sometimes 70 or 80 genes, where having a mutation in any of them is going to increase your risk. There are genes that work alongside the BRCA genes, for example, and all of those genes increase risk for a similar constellation of cancers too. And so the whole idea is getting that information and putting the plan in place, but we're learning more and more about these newer cancer genes. And so as a result, our understanding of what it means to have them has changed over time too. Steve Wartenberg: So it sounds like it's impossible for anyone or even any primary care physician to know every single genetic mutation, but talk to your family doctor, get a thorough family history, and if there's any red flags, come to see you. Leigha Senter, MS, CGC: Yeah. Yeah, that sounds like a good plan. Steve Wartenberg: Okay, we're going to take a quick break and when we get back, we'll dive into the actual process of a genetic screening test, what it discovers, and then how Leigha uses that information to help people. [Text on screen: #ChooseTheJames Dr. David Cohn Interim CEO & Chief Medical Officer] David Cohn, MD: You didn't choose cancer, but you can choose where to treat it. [Text on screen: #ChooseTheJames Dr. Uma Borate Hematology] Uma Borate, MBBS: And when you choose The James at Ohio State... [Text on screen: #ChooseTheJames Shavonda Neal Nursing] Shavonda Neal, MS, RN, OCN: You're picking a team of experts who understand there is no routine cancer. [Text on screen: #ChooseTheJames Dr. Carolyn Presley Medical Oncology] Carolyn Presley, MD: You're opting for care from a highly specialized team dedicated to treating one type of cancer, yours. 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[Text on screen: #ChooseTheJames Annie Trance JamesCare for Life] Annie Trance: And you're choosing access to The James world class clinical trials, dedicated support services, and an unmatched survivorship program to support your life after cancer treatment. David Cohn, MD: You didn't choose cancer, but the choice of where to treat it is clear. [Text on screen: The James The Ohio State University Comprehensive Cancer Center cancer.osu.edu/ChooseTheJames] [Text on screen: Steve Wartenberg Host The James Cancer-Free World Podcast] Steve Wartenberg: We're back with Leigha, and we're going to talk about the actual genetic test and how is it done. I don't even know, do they take blood, saliva? Do they use magic? How do you do it? [Text on screen: Leigha Senter, MS, CGC Licensed Genetic Counselor OSUCCC - James] Leigha Senter, MS, CGC: Always a little bit of magic. No, we have lots of options now, but generally speaking, once we have determined what a person's options are for genetic testing based on their family history, their personal kind of goals for what they want to get out of the genetic testing, most of the testing for the inherited things is done using a blood sample or a saliva test even. So a lot of our appointments, sometimes we're sitting together in the same room, but we often do them via video or telehealth. And in that situation, we can handle things remotely. So we can ask the genetic testing lab to send materials to a patient at home where they can spit into a tube and send it back. Steve Wartenberg: Oh, this concept of doing it remotely makes it so much easier for patients, particularly since The James is so good. And you get patients from so far away, they don't have to drive 200 miles here three times. They just can meet with you remotely over video. And that makes it so much easier. Leigha Senter, MS, CGC: Yeah, it really has increased access. And even just for people who don't live far away, but they have transportation issues or their job isn't very flexible and they can carve out a shorter amount of time because they don't have to drive here, it's really allowed patients to access us easier. Steve Wartenberg: So I do know that some of your research centers on, once you've determined that a person that you've done this genetic screening on, has we'll just say Lynch or BRCA, you've become an expert. And how do you then communicate with not just that person, but help that person communicate with their family to, I'm not exactly sure, spread the news and help them to figure out if they need to be tested? [Text on screen: Leigha Senter, MS, CGC Licensed Genetic Counselor OSUCCC - James] Leigha Senter, MS, CGC: Yeah, it's a really interesting situation. We spend a lot of our time identifying these mutations in a family, and somebody is always the first one to test positive. And then our next step is to tell that person that they need to share all of this information that we just gave them with as many family members as possible. Because it's that cascade of events, actually, we call it cascade testing then is where our real potential is to keep people from getting cancer because we need to identify that they have a high risk and then put that screening and risk reduction plan in place. And that step of telling all of your family members this new information is not easy for most people. And it's impacted by so many different things. Your family dynamics. And if you happen to have cancer, you've also got a million other things on your plate. And so some of our work has been in finding ways to make that process easier for people. So we have video messages that patients can forward along with a text message that give a lot of good information in two minutes time to at least get the conversation started. And a lot of the genetic counselors will write letters to family members that the patient can literally just copy or email on. But that piece of telling family members is really at the crux of cancer genetics. That's why we do what we do. Steve Wartenberg: So again, we'll just use a woman who has the BRCA, how far out does she have to cascade? Her parents and children I'm guessing pretty certainly, because that's a direct line. But who else? [Text on screen: Leigha Senter, MS, CGC Licensed Genetic Counselor OSUCCC - James] Leigha Senter, MS, CGC: We really recommend that you go as far as you can go. If you're doing it in an exact stepwise fashion, which doesn't always happen. But of course you would start with your closest relatives and then sort of branch out as you determine who in the family also has the mutation and who doesn't. Because then of course, anybody, any of their offspring don't need to be informed. But I find that most families don't fit a nice symmetric picture. And so if you are only in touch with one of your 20 cousins, tell that person and then hope that they share with the people that they are linked to. Because the information can impact generations in very distant branches of the family. Steve Wartenberg: Now people are spread out all over the country, and some could even live abroad. So say we're here in Columbus, you have a relative, well, I have a relative in England, so where would my sister go if there was some indication she should get a test? And how would that... Would you be connected to that test? Leigha Senter, MS, CGC: Yeah, so what we would do is give you the pieces of information that are most critical to share with your relative in England. We also would identify places in England that would offer the equivalent test to what we would do here. There are some areas of the world where that's really hard, where they don't have cancer genetics readily available. But we're lucky enough to have a very broad network of research colleagues and even clinical colleagues that we can reach out to to try to get patients connected. Steve Wartenberg: So you'll find somewhere for someone to go. And what I think I've learned is here in Ohio, there are places down in Appalachia that may not have genetic testing facilities, but you can figure out a way to get those people here. Leigha Senter, MS, CGC: That's right. Steve Wartenberg: Connect with their physician to get their blood or saliva here. [Text on screen: Leigha Senter, MS, CGC Licensed Genetic Counselor OSUCCC - James] Leigha Senter, MS, CGC: Yes. And now that we rely on telehealth so much, sometimes, I'll be seeing family members via video. They live two hours away. They're not close to a medical facility, but we can handle things through the mail. And then when it comes time to doing their screening, they don't mind coming here for their once a year appointment or something. But we can make it those critical appointments they need to travel for and the rest we can handle at home. Steve Wartenberg: Wow. So in an extended family with like three generations in a row have like six, seven, or eight kids, that cascade could be a hundred or more people. Leigha Senter, MS, CGC: It can. Yeah. And it's fun to get to meet all the different family members if we're lucky enough to do that. But yeah. Steve Wartenberg: Maybe they could just all have a big reunion and can test everyone in the same day. Leigha Senter, MS, CGC: I have been to a couple of reunions before. Yeah. Steve Wartenberg: And you get to eat some good food as well. Leigha Senter, MS, CGC: I do, yeah. Bonus. Steve Wartenberg: One of the perks of the job. So we've talked a lot about having the right facilities to do this, and we're lucky here in Columbus, we have The James and you are part of one of the biggest, best genetic counseling programs in anywhere. So what does it include, like how big of a program and what are some of the specialties and options and things that people can get here? [Text on screen: Leigha Senter, MS, CGC Licensed Genetic Counselor OSUCCC - James] Leigha Senter, MS, CGC: Yeah, we're really lucky that we have about 12 genetic counselors on faculty supporting just the cancer program. And over the years, genetic counselors have kind of spread out within The James. So almost every specialty that you might be seen in, you'll have a genetic counselor available to you who primarily specializes in GI cancers, or primarily specializes in gynecologic cancers. And so you get a really deep knowledge in doing that. But the downstream step of all of this, which is so important, is that all of the screening that we're recommending we have access to here. Steve Wartenberg: Yes. Right. Leigha Senter, MS, CGC: So it would be pretty unsatisfying to identify a family with a hereditary predisposition, know that they needed specific cancer screenings and then not be able to offer it to them. But we don't have that problem. So it's great. Steve Wartenberg: But someone who lives in rural Alaska, who's a family member of someone you diagnosed here may have that problem. Leigha Senter, MS, CGC: They might, although this is where we rely on our network too. Genetic counselors are pretty connected. It's not a huge profession. And so I might call my colleague in Alaska and say, "Where can this person get a breast MRI?" Steve Wartenberg: You'll never leave someone hanging. You'll always find them somewhere to go. Leigha Senter, MS, CGC: Yeah, we're pretty diligent about that. Steve Wartenberg: So the way you say that and you're kind of your passion toward it, that must be kind of the reward. What is that like when you've helped identify a family with BRCA or Lynch and you've screened lots of relatives and you actually are saving lives? What is that like? [Text on screen: Leigha Senter, MS, CGC Licensed Genetic Counselor OSUCCC - James] Leigha Senter, MS, CGC: It's why I do this work. I think it's why most of my colleagues would say that they do this work. The potential to intervene in a family's cancer history is really unique. And I don't take for granted the possibility of meeting lots of members of the same family. You sort of get to know a lot of them from a bunch of different angles. But sometimes people will think that telling a person that they tested positive is really difficult. How do you do that all the time? But I sort of think of it as a gift to the family. This is information they didn't have before and we can do something about it that may really impact them and their family members. It is very great to be able to tell a person in a hereditary family that they didn't inherit what we know is there. There's no getting around that. That's really great. But it's meaningful work and we learn a lot from the families. Steve Wartenberg: I would think you get mixed reactions from people that you tell that they're positive. Some are relieved, some are a little stressed out, and some are both. But like you said, that knowledge is powerful and can help them to either prevent cancer in some cases or catch it in the very, very earliest stages. Breast cancer in the earliest stages is more than 95% curable. So you can use that information for good. [Text on screen: Leigha Senter, MS, CGC Licensed Genetic Counselor OSUCCC - James] Leigha Senter, MS, CGC: Right. And these days, sometimes a cancer patient's genetic test results also impact their treatment course and what medicines they may take. And that's another big part of this too. So in addition to having a legacy for your family, really, it's also something that may be beneficial for the patient right now. Steve Wartenberg: Wow. That's a whole nother topic for a podcast. How identifying the specific mutation leads to the precision cancer medicine that gets better results in cancer. Leigha Senter, MS, CGC: That's right. Steve Wartenberg: So that's a whole another way that geneticists are part of the cancer process and treatment. Leigha Senter, MS, CGC: That's right. Steve Wartenberg: Wow. So you do a lot. Leigha Senter, MS, CGC: Yeah. It's exciting. Yeah. Steve Wartenberg: Well, thank you for sharing all that. And this is just great, useful information that people should know. And so the takeaway is to know your family history, talk to your family physician about it, and if there's any issues, you know where to go. Leigha Senter, MS, CGC: That's right. Steve Wartenberg: Okay. Well, thanks for joining us and filling us in. Leigha Senter, MS, CGC: Thanks for having me. [Music playing] Steve Wartenberg: This podcast is brought to you by The Ohio State University Comprehensive Cancer Center, Arthur G. James Cancer Hospital, and Richard J. Solove Research Institute. For more information, check out our website, cancer.osu.edu. [Text on screen: The James The Ohio State University Comprehensive Cancer Center Cancer-Free World Podcast cancer.osu.edu]