Myriad Oncology Live episodes are recordings of an open-forum webinar hosted by Dr. Thomas Slavin. The opinions and views expressed in this recording do not necessarily represent those of Myriad Genetics or its affiliates. To participate in a future recording, visit myriad-oncology.com/myriad-oncology-live for a list of dates, times, and subjects.
Myriad Oncology Live episodes are recordings of an open-forum webinar hosted by Dr. Thomas Slavin. The opinions and views expressed in this recording do not necessarily represent those of Myriad Genetics or its affiliates. To participate in a future recording, visit myriad-oncology.com/myriad-oncology-live for a list of dates, times, and subjects.
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0:00:13.3 Speaker 1: Welcome. This episode of Inside the GENOME is a recent recording on Myriad Oncology Live, a webinar hosted by me, Dr. Thomas Slavin, chief medical officer from Myriad Genetics. The opinions and views expressed in this recording do not necessarily represent those of Myriad Genetics or its affiliates. To participate in a future recording, please visit Myriad Live for a list of dates, times, and subjects. I look forward to exploring the world of genetics with you all. Hello, everyone, welcome to Myriad Oncology Live. Was a little housekeeping to start. If this is your first time on, yeah, we do theme-based discussions, today is on, let's talk male breast cancer. We had a good one about two weeks ago or so with Dr. Todd Cohen on prostate cancer genomics. Next week we have Dr. Holly Peterson from the Cleveland Clinic will be on talking about translation of polygenic risk scores into clinical care, we'll also have her own ED on and she will help with some of that conversation. And we have more topics already set up. I know the times have been set up, we'll have to get them posted. Natalie, I see you on, thank you, I know you were looking into maybe one more, if you could touch base with Morgan, if you have some time for that, we can get these all posted, and I'll reach out to Morgan after this as well. And yeah, hopefully, people can see the new topics. So we have November and December.
0:01:52.1 Speaker 1: And we'll take some time off over the holidays, obviously, and have a little bit of break. But we do have it built out through at least the end of the year. So thanks for coming on today. We have male breast cancer as the focus and we have two external special guests. I very much appreciate them coming on, and they are also coordinated care of Natalie, so thank you. And we have Bret Miller and Michael Singer. And so Bret is the founder of the Male Breast Cancer Coalition, and Michael is a member. And in addition, so we'll take a second and have them talk about their stories. We also have Shelly Cummings who's on. And not only is she running the chat today, as always, so if you have chat questions... If you have questions, feel free to, A, unmute yourself, B, you can... If you don't wanna unmute yourself, send them to Shelly. But she also has a little bit of an update on male breast cancer, what's been going on on the clinical and research side in terms of genomics and genetic testing. I should also mention before I forget that we do record these now. And that's just been on request of a lot of people that wanna listen to them after, they couldn't make the times, and we are posting them up on the podcast Inside the GENOME, so yeah, Bret and Michael at some point this will be up there as well, so you can feel free to use it however you want.
0:03:32.6 S1: And we are also... So anything that says Myriad Live in front of it, is from one of these webinars, and if it doesn't say Myriad Live, we just have it as a regular podcast. And so like this was the emerging role of genetic counselors in tumor testing with Leigha Senter from Ohio State, and so that's a good one. These tend to be about 15 to 20 minutes, and then the Myriad Oncology Lives are usually an hour. So thanks all, and without further ado, let me have Bret and Michael introduce themselves. So I don't know if anyone's wanting to go first. But maybe whoever's at the top of my screen, Michael, I see you're at the top. If you wanna give a little backstory of yourself and then Bret.
0:04:22.9 Speaker 2: Okay, sure. Well, my name is Michael Singer. I was diagnosed at age 50 with stage two male breast cancer. At the time of the diagnosis, back in 2010, I'd never heard of a man getting breast cancer. My only familiarity with breast cancer is I had an older sister who died of metastatic breast cancer two years prior. So when they told me that I had breast cancer, I thought I had a year to live 'cause that's all my sister survived. And going back to the beginning, I didn't tell anybody I had breast cancer, I kept it a secret. If anybody heard that I had cancer, I told them it was chest cancer 'cause I couldn't say the word breast 'cause I was embarrassed and stigmatized because I felt I had what I was brought up to believe was a woman's disease. So I lived in the closet, so to speak, for two years. And then one day, I was seeing a teaser on TV from the Katie Couric show, which was a New York City based TV show. And on that show they had two gentlemen, one being Bret Miller, who's here with us today and the other being Richard Roundtree. Who if, I don't know if any of you here are old enough, but when I grew up, Richard Roundtree was this cool action hero, African American, and the dude was cool.
0:05:48.4 Speaker 2: And here are these two guys on national TV talking about male breast cancer, and along with them, they had an oncologist from Sloan Kettering, Dr. Clifford Hudis. And I was like, "Oh my God, they're talking about me. Why am I so embarrassed? I'm not alone." And right after the show was over, I reached out to the Male Breast Cancer Coalition which Bret co-founded. And they invited me to a conference in New York City. And I went there and I met my first 10 men with male breast cancer and they were all different stages, early-stage, metastatic, some had mastectomies, some didn't have mastectomies. And it was life-changing because at that point I went from embarrassed to empowered. And along with Bret and the Coalition, I just started going all around the country basically doing health fairs, conventions, conferences, high school, senior centers, national TV ads, magazine ads.
0:07:03.2 S2: And I've been advocating for the Male Breast Cancer Coalition for coming on close to eight years now, seven years, and it's been an amazing journey. I've met so many interesting people. Myriad was one of the big factors in my life early on, because after I got diagnosed and had my mastectomy, they sent me for genetic testing here in New York, and Montefiore was using Myriad at the time and had the genetic test, and believe it or not, I came back negative for BRCA. And back then 2010, there weren't too many panels they were testing, I thought there was a connection between my sister and myself and there wasn't, so I'll talk more about it, but I'll let Bret introduce himself.
0:07:53.2 S1: Yeah, thank you.
0:07:54.1 Speaker 3: Hello, Bret Miller, yes, co-founder of the Male Breast Cancer Coalition. It's been an honor to have Michael with us, like I always joke with him that he didn't talk about it for almost three years, and now I can't get the guy to shut up. [laughter] But he's one of... He's our best advocate out there. He's willing to help everybody, so we love you, Michael. A little bit about me. I was 17 when I first found my lump. Doctors at the time, told me that it was calcium buildup, I was going through puberty, it would dissipate and go away. It's nothing to worry about at the time. Fast forward seven years later, when I was 24, my parents forced me/encouraged me to go get a physical since it had been almost seven years. Throughout college not having insurance as a broke college student and my parents being self-employed insurance is kinda... In the United States, it's not the cheapest thing to try to keep, but luckily, with my job that I've been at for close to 20 years now, having insurance out of college, I've had good health insurance through them.
0:09:06.9 Speaker 3: So they encouraged me to go get a physical. Upon doing so, the doctor at the time was pretty much telling me that everything looked great. "Don't worry about anything, we'll get the blood work back to you. And we'll talk in about a week once we get those labs back." I had to stop him before he was pretty much out the door to ask him to come back and check this lump that I've had under my nipple for almost seven years, because in a physical for a male, the doctors do not check the breast. So it was something that I had to bring up to the doctor, something that we are currently still working with a lot of doctors to change to try to do a quick little feel during a physical for a male to just add it into an exam.
0:09:49.2 S3: He immediately sent me... Came over checked it out, sent me to go get some scans. Unbeknownst to myself, I walk into the women's clinic, I was not told where I was going, I was just told to go to this address, greeted by name, asked to fill up their questionnaire of name, address, insurance, when was your last menstrual cycle, and are you pregnant? And then given the pink gown, which I know Michael went through the whole process as well, had an ultrasound, then was ushered down the hallway to get a mammogram even though it wasn't part of the, on the docket for the scans. The female doctor was there to encourage and said that it would be better for me to go do that, so I didn't have to waste time, take off work and come back. So I had an ultrasound and a mammogram.
0:10:39.1 S3: Met with a surgeon. They just said, "You know what? Let's just take the lump out based on what I can see on these scans and the time that you've had it, it looks like calcium, but we're just gonna take it out." And so they did a lumpectomy on it and next day I got the call that it was breast cancer. Met with that surgeon again, finally, and just didn't like the feel of bedside manner stuff. The next surgeon we met with, Dr. Lon McCroskey, he was the one that really encouraged me to start speaking out. He said that he had performed the surgery on a dozen men before but most of them took time off work, healed up from the surgery, went back to work and don't talk about it. If I was willing to share my story at my age, that he thought that I could be a face of male breast cancer and help encourage others.
0:11:31.4 S3: So I had a... In talks with him and a plastic surgeon about reconstructive just 'cause I didn't know what to... What was I going to go through? I'm 24 years old, I work around a pool, I'm gonna be losing a nipple, breast so on, to the tissues and stuff. What's it gonna be? And just in talking with those two doctors, I just realized that I'm not gonna change anything. I'm gonna go through the surgery, no reconstructive, this is what I... This is who I am now, this is what I'm gonna... This is how I can have an impact. If I tell somebody I have breast cancer, and they go, "Men don't get breast cancer," I'm comfortable with lifting up my shirt and just showing them and be like, "Then what's this? Yes, we can."
0:12:10.7 S3: And so we started originally with the Bret Miller 1T Foundation, which has now evolved into the Male Breast Cancer Coalition, which we are a global organization. We have men from all over the world sharing their story. And as you can see with Michael and stuff, I helped encourage... He was one of the few that I've helped encourage, and it just feels great to do that, to be able to give men a voice. So thank you for having us on. I know that we've done... My mom was able to do the Myriad at the time I had the genetic testing, I do not have the BRCA1 or 2 as well, mutation. And then a few years later, my mom... They tested my mom because health insurance wouldn't cover another genetics test. So they tested my mom and she didn't have any of the genes either. There was an outlier that they think, but we do have the 13 female cousins on my mom's side that have had breast cancer but they still haven't pinpointed anything yet, but. Yeah, I think, touched everything.
0:13:12.6 S1: Yeah, yeah, no, that's amazing. And so, what... The Male Breast Cancer Coalition, what would you say the main purpose is, what are some of the bigger goals at the moment?
0:13:26.0 S3: We're an advocacy group for men and a big support system for men, 'cause I've made it my mission that I didn't want any other men to feel alone when you hear the words you have breast cancer, as I did when I got that phone call. I was literally by myself, and the doctor just calls me and tells me the preliminary pathology reports are breast cancer, and he'll read the reports in three or five days and get back to me. And that was pretty much it. It's just kinda, it's the... Some of the actions of some of the doctors towards men, it just, it catches you off-guard and you don't know how to react to it. A lot of men don't know that they're having to go to the women's clinic, so it's just so we can build the awareness of what's gonna come your way. It would make men feel more comfortable about their future path that they have to go down and just be more aware of your body, be your own best advocate.
0:14:21.7 S3: If you feel a lump, go say something and quit being as a male, seven years, I had the lump for a year and a half, almost two years, I had a discharge from my nipple, I didn't talk to too many people and say anything about it just because I thought that it was the calcium buildup that I was told about for so long, and it just dissipating and going away, but we need to understand and know the symptoms, we need to be aware that men can get breast cancer too. So if you feel a lump, say something, go do something and quit being so stubborn about your health as a male and get to a doctor to make sure and checked out. Michael, do you have anything that you wanna add about?
0:15:00.8 S2: Yeah, sure, so the Coalition has done an amazing job of making male breast cancer start to become mainstream. Like I said in the beginning, I was embarrassed, but the Male Breast Cancer Coalition, the webpage, shares hundreds of stories of men with breast cancer and how their journey began and how they are now. And if you are someone who's been diagnosed, we run a monthly group for men, support group, and just last week we had two guys just Google male breast cancer, came to the Coalition, were able to dial into our support group, and it gives them a feeling of you're not alone. It's not just a woman's disease, it's a people's disease. And again, in the beginning, I thought I was a freak. I was like, "Breast cancer, how can I have breast cancer? I'm a man." And then until you get into hearing the stories and talking to the doctors and finding out that, "Yeah, it's a people's disease, men and women, both get diagnosed."
0:16:05.2 S2: Over 2650 men are diagnosed every year in this country alone, that's based on statistics from the American Cancer Society, but unfortunately, 530 of those guys are gonna die due to the latter stages of their diagnosis because as Bret mentioned, they don't know the early warning signs, they don't know to look for nipple discharge or an inverted nipple or redness, scaling, swelling, inflamed lymph nodes, they have no clue, and by the time they do tell somebody or go to the doctor, in some cases, these guys are already stage three or stage four fighting for their life. Another thing that the Coalition provides is resources for men and their families. I know Bret doesn't want to say it, but Bret does a fantastic video on how to do a self-breast exam for a man, so if you go to the website and you don't know, he walks you step through step, how to do the breast exam. And if you haven't been there, and you wanna see Bret's six pack, go to the thing and see how he does it. The Coalition also has handouts, and we've been to, like I said, many health organizations and San Antonio conference and ASCO, and we have cards on how to do a male self-breast exam as well as for a woman to do a self-breast exam. And if you go to the website and look at it, it's in close to 20 different languages so far with new languages being added all the time.
0:17:37.7 S2: So for the people around the country, we have a large foot in India with the doctor who's over there and she's been distributing these cards to everybody, and in India, there are many languages and she's interpreted them all, and it's just... It's growing. In the beginning, it was small, and now as Bret said, we are international, we've got men in so many different countries, and besides the support group we do here in the US monthly, there's an international support group that's held monthly, and we'll get guys from all over the world depending on the time zone, sometimes we move it to where it's better for Australia, sometimes we move it to where it's better for Japan, and just really getting the word out there, that men have breast too.
0:18:26.2 S2: And I lived through everything Bret talked about, going for the mammogram or as I like to call it a manogram where I was segregated from the women, we're all wearing the pink gowns, my breastfeeding, menstrual cycle, pink forms, all of those questions, and that's a lot to do what causes the stigma for men. And let me tell you, I'm in the Bronx, and I do a lot of health fairs in the inner city and the African-American, Latino community, this is like taboo, they don't wanna talk about their breasts. We do health fairs, the guys look at us like we are freaks, and they're like, men have breast too, and they stand in front of me touching their breast like, "What are they talking about?" And I find most of the spouses and significant others come up to us and ask us for the information. The guys stand away from the table because they don't wanna be associated with something called breast cancer.
0:19:28.0 S1: Yeah. What kind of news spots have you been doing? Have you been getting some national media and international media to raise awareness as well? It sounds like you're working a lot with local doctors, going to conferences. I was just curious what else.
0:19:41.1 S2: Well, right now, this meeting we're having on Zoom actually is what we call the third week of October as Male Breast Cancer Awareness Week in the United States. So men in all 50 states have met with with their politicians and got proclamations, and it gives us an opportunity to get the news coverage, to do the newspaper interviews and get faces on TV. I mean, we have a private website just for the men, and it's amazing, all of the different news clips and interviews that come in, especially this week. But you know what surprises me, Tom, is that breast cancer is all year long. It's not just October or Pinktober, it's all year long, especially for the men we have... Or the women we know who have metastatic breast cancer. These people are dealing with it every day of their life, whether it's different drugs they are taking or the side effects they're taking. I'm early stage. I did eight years of a drug called Tamoxifen, which was an estrogen blocker, and the side effects were brutal for me. I know Bret had to switch to a different drug, and he can talk about that, but we're getting...
0:20:56.7 S2: Especially when we go to San Antonio Breast Cancer Conference, we have people from all around the world stopping by our booth, in ASCO, Brett and I were there. We met with so many different people and I think we're making a difference. I really do. We're here having a Zoom with you today, and to me, that's another step. That's another difference. We have at least 22 people here today that they're gonna hear about male breast cancer and maybe talk to their father, their uncle, their brother, their son. If you have cancer or especially breast cancer in your family, whether it's on your mom's side of the family or you dad's side of the family, that's the conversation that's gotta be held, whether it's Thanksgiving, Christmas or party, because most people who are talking about breast cancer are the women at parties and they can talk to it comfortably with other women. It's very difficult for me and Bret to go into a party and grab a group of guys and say, "Hey, you guys, have you done the self breast exam? Is your nipple inverted? Do you have discharge?" It just doesn't happen. The guys are gonna walk away from us, guaranteed, so it's... This is a difference. We're making a difference for sure.
0:22:10.7 S1: Yeah, that's great.
0:22:12.4 Speaker 4: I have a question.
0:22:15.2 S1: Yeah.
0:22:15.5 Speaker 4: So Bret and Michael, in your experience with different medical professionals, what would be your advice to those that are on this call in having this conversation and things they could have done differently or a different approach with having the conversation or how you were treated?
0:22:35.1 S3: Well, I mean, my... Like I said, my primary care, when I first got the diagnosis and stuff, I went back to him afterwards, and I asked him about adding a breast exam for a male in a physical, and he basically was telling me that statistically it's not worth his time to add a breast exam in there for a male that doesn't have a hereditary pass. I got tested. He knew that I had got the genetics test and I don't have a hereditary pass, I don't have the gene. There are female cousins, but they're distant. They're second, first, second, third cousins or so on, they're... So it wasn't like a direct line, and it was very disturbing to hear that even though I'm already paying to see him, that it wasn't worth his time. So it's just one of our biggest things is even if they don't do an exam, at least bringing it up in an exam, just being like, okay, it's something you can do on your own time, is check for lumps in your breast. And it's just like Michael had said, and he said it a few years ago, and it's really stuck with me ever since that it's not a women's disease, it's not a men's disease, it's a people's disease.
0:23:46.2 S3: And until we can get all of the big, I've gotta say, conglomerates or so but until we can get it from them, everybody from... Stop saying women, women, women and changing just the verbiage, either adding men to the conversation or changing it to, are you a person diagnosed with breast cancer or something along those lines, is when we'll get the impact. I just keep thinking what type of impact there could be if you have a breast cancer commercial during a football game, and you include men in the commercial, however, and say in the conversation, men with breast cancer and men can get breast cancer, something like that, just the impact that could have is how many men are watching football games, and just... And if you could get that, then just the impact that we can change the stigma behind it and just be more welcoming and understanding that it can be... It can happen and just not make the men feel embarrassed about being diagnosed with breast cancer.
0:24:50.9 S2: And Shelly, to further answer that question, I think doctors, medical professionals, the family history intake is so important when you're meeting a doctor. If you're going through your first time and the doctor doesn't know your family, knowing that you had a sibling who had breast cancer or prostate cancer or heart disease, I think these should all be red flags or just a signal for a doctor to look into it further. "Oh, you had a sister with breast cancer, your mom had breast cancer. Did you know a man can get breast cancer?" And look, they do the exam, look in your ears, look in your eyes. If you're a man, you get prostate check. It's another minute or two to check out breast. If it's an inverted nipple, as soon as the guy opens his shirt, you're gonna see it. If there's a lump, like I had, just ask, doing... Palpating the breast or something, they're gonna find that or somebody's gonna say something about it.
0:25:56.0 S2: But in addition to that, the medical field, in 2019, the FDA did a draft guidance for the industry developing clinical trials and drugs that they have to include men in their clinical trials. And if they don't, they have to come up with a darn good reason as to why men aren't being included. So this is also forcing the medical industry, so to speak, to recognize male breast cancer.
0:26:30.0 S1: I'm very interested in the treatment, because it's actually something I haven't really thought about a lot. We think about in genetics, a lot of times we'll find genes in somebody's family, and we'll recommend guidelines for men. But then going through the actual treatment and going through the anti-hormonal therapies on the back end, what were your experiences there? Because yeah, that is very hard, for sure on women, and I really don't know. I don't know if anyone's an expert on the call, but feel free to chime in, the effects of these kind of treatments on men.
0:27:07.8 Speaker 5: I can tell you something about my experience. I'm from the Netherlands, from Europe, also with male breast cancer.
0:27:16.0 S1: Thank you. You can introduce yourself. Yeah, thank you.
0:27:17.0 Speaker 5: I'm...
0:27:19.0 S1: How do you say your name?
0:27:20.0 S5: [0:27:20.1] ____.
0:27:22.0 S1: Thank you.
0:27:25.4 S5: And even in the Netherlands, in the GP guidelines it's written, when there's something wrong, you feel something below the nipple of a man, immediately prescribe to the hospital, immediately. That's the good story. The bad story is they don't do it. My GP didn't do it. She said okay, she said there's nothing happening. But I didn't rely on it, so I went... I insisted on getting an echo, an ultrasound in the hospital. The first was wrong and then at another hospital, in two weeks time, I had the diagnose. So it was very fast. So it's like you said, Michael and Bret, that people don't think about it, even if it's in the guidelines. The second thing is the hormone therapy. I took tamoxifen for 11 years. And I have to say that because with men, male, the level of estrogen naturally is low, so if you're lower, a low concentration of estrogens, the chances you get much side effects on men are much lower than with women. I took it for 11 years and didn't have any problem with it.
0:28:42.0 S5: But I've also got a question to you, Thomas. I've been a 6 1/2 year consultant for Oncotype and do work for EndoPredict now at this very moment. When I had this, I was discussing with my oncologist, with who I have a meeting by the way next Thursday about EndoPredict, and I was discussing with him, "What should I do? It's 12 years ago. I know there are some genomic tests, they're on the market. What should I do before I decide for chemotherapy?" And then he said "Well, based on the publications, there are advance genomic testing in males. If it would be low risk, are you gonna do it? Are you gonna decide for no chemo?" And then I looked at the publications, I said, "12 years ago" and then I said, "No, no, no, I don't wanna take the risk." So I would like to be updated what's at the moment, what kind of investigation are there concerning genomic testing and male because there are some...
0:29:52.0 S1: That's a great question. And we are privileged to have Dr. Conway.
0:30:00.8 S5: Oh, it's Ralph, okay.
0:30:00.9 S1: Ralph, yeah, I don't know if you wanna unmute yourself. He's one of the founders of EndoPredict here. So if there's anyone that knows, it's Ralph. [chuckle]
0:30:11.0 Speaker 6: Thanks for the introduction and...
0:30:12.4 S5: Hey, Ralph, long time no see. [chuckle]
0:30:13.3 Speaker 6: Yeah, nice to see you. [laughter] Because we know each other yeah. I worked these years on gene expression testing, and I'm very much close to EndoPredict, as you said I'm one of the inventors of the test. And I think it's very interesting what you said, Michael, with regards to clinical studies, because this was a challenge for us because we were already a couple of years ago interested in validating our test, our gene expression test, in male breast cancer. But the challenge was the standard trials were always with women. Men were excluded, so there was no option. And doing a specific analysis in male breast cancer, it's very rare, the disease, and it was a challenge to identify suitable cohorts to validate. So that's why I really appreciate your comment saying that at the very beginning of clinical trials, this male breast cancer should be included, and there's no reason for me to exclude such patients from the trials.
0:31:50.9 S1: Yeah, agreed. And I haven't seen data for or against... Others, again, feel free to chime in if they have... Showing major differences between male versus female standard types of invasive breast cancer, which are usually still the more common types, like invasive ductal cancer. But I don't know if anyone on the line has any further comments there, but yeah, if there's not in my mind proven major underlying molecular differences, you'd think that a lot of these gene expression assays that really are looking at how revved up cancers are in the cells that you're testing are should work pretty similarly, I would think.
0:32:37.0 S2: Thomas, Dr. Sharon Giordano and Dr. Fatima Cardoso have done the largest study on male breast cancer, but they have found many differences. The first obvious difference is that close to 90% of the male breast cancer is ER positive as opposed to women's breast cancer. The other thing which is glaring is that the study halted because funding stopped because, I don't wanna be a wet blanket, but maybe there's not the big money in male breast cancer as there is in female breast cancer because they treat me and Bret the same way they treat women, mastectomies, hormone therapy. They're not doing anything different for us. When I was put on Tamoxifen, it was a 20 mg pill no matter what my weight was, no matter what my stage was, and that's across the board, and Ralph said, he didn't have any side effects. God bless him, because we participated in a clinical trial with Dr. Deanna Attai on collateral damage for men, and this is men who've had breast cancer whether the collateral damage was physical, psychological.
0:34:03.4 S2: It was an amazing study, and she presented these findings at the last Male Breast Cancer Coalition meeting, which had to be virtual this year due to COVID. But they're starting to include us in studies, but the last time I went on to clinicaltrials.gov here in the US for stuff and look, when you start at the phase one trials, they include a couple of men. When you go to phase two, that number gets lower. You get to phase three, even lower. When you get down to phase four, you're talking single digits like one or two. So the new draft guidance, we're hoping to see a big change in this because although... Look, Bret's a young dude. He's a new father. He's got a long life hopefully to live. I'm in my 60s, and the thing is like, "Oh, men don't get breast cancer until they're 70s and 80s." That's a lie. Bret was one of the youngest guys I've met, and most of the guys I meet are in their 40s and 50s, and we do have guys in their 30s and 20s. So until the medical field starts to include us more now that they have to say why they're not including us, hopefully, we'll get some answers to these questions because I've heard other people say, "We're dying for a cure."
0:35:30.1 S2: When I see these guys, I went to a funeral just this past week for a gentleman named Michael Kovarik. He was an advocate for the Male Breast Cancer Coalition. He was an advocate for METAvivor, which is another not-for-profit that just focuses on funding the research for metastatic breast cancer. There has to be a change. We wanna see not just men. We wanna see men and women go on to either live great lives or treat metastatic breast cancer as a chronic disease where people can function and still raise a family and have a life, because we're seeing too many men and women at young ages just not surviving this disease.
0:36:13.8 S1: Yeah, well said. No, we certainly need more research and yeah, inclusion is key to all that. I wanna turn over to Shelly for a few minutes just for a brief update 'cause she has a nice slide deck for the audience. But yeah, I don't know, Shelly, if you could do a quick update, maybe five minutes or something, just to give us more time. Eight minutes. I think you're on mute.
0:36:45.8 S4: What area of my slides do you want me to cover?
0:36:48.8 S1: Probably the... Maybe the... What's going on with the polygenic risk score. I think that's pretty interesting. That's kind of new to the audience.
0:36:56.8 S4: Okay. Can you tell me what you can see?
0:37:01.3 S1: There's nothing really... Yeah, it looks like your computer.
0:37:05.8 S4: Just my computer. Okay.
0:37:11.2 S1: Yeah, we can see it now.
0:37:12.5 S4: Right here?
0:37:13.4 S1: There's nothing really... Yeah, the National Comprehensive Cancer Network, they haven't made any major changes off the top of my head over the last few years to male breast cancer screening.
0:37:26.8 S4: No, they have not. And as a matter of fact, the recent revision to the gene table doesn't even list the cancer risk associated with male breast cancer for BRCA1 and 2. And BRCA2 is the primary culprit for male breast cancer, so I was a bit disappointed when I saw that update because they list pancreatic and they list melanoma, but they don't put anything for male breast cancer. And I think that's a big omission on their part. There's some language in the discussion section back of NCCN, but I don't really think the doctors look at that discussion section as much as they look at the algorithm.
0:38:11.0 S1: And as Bret and Michael pointed out, a lot of men don't have gene mutations obviously that... And then there's really no... Pretty limited guidelines. I mean, there's really no guidelines, if you have a strong family history of breast cancer or even if you had a brother and a dad with breast cancer, I mean, it's hard to... If you're... Don't test positive, there's really not a lot to lock into on how to manage that person.
0:38:36.7 S4: Yeah, and when I was thinking about Bret's situation, even for known males that have an altered gene, clinical breast exams are to start at age 35. So, it seems like that would definitely not have been helpful for some of these males that might get it at at younger ages. And I know that these experts are using the numbers when is the majority of male breast cancer going to occur, which is in the 60s and 70s for men, but there certainly are distinct exceptions to that. So, this slide that I have up in front of you now is just to highlight a few activities that are happening in the research area for male breast cancer. And this was a study that came out of the Simba group with consortium of investigators of modifiers of BRCA1 and 2, and honestly, this group has been the largest to look at BRCA1 and 2, and it was published in JCO in 2017. And what they did is they genotyped male carriers of either BRCA1 and 2 who were part of that Simba consortium trying to look at the combined effects of established breast and prostate cancer associated with BRCA1 and 2. And they also were looking at a weighted polygenic risk scores or SNPs to see if the SNPs influenced the level of cancer risk for either male breast cancer or prostate cancer.
0:40:27.4 S1: Yeah, and these SNPs, these are just background genetic factors that, some live in genes, many do not, they're just... Like BRCA1 and 2, for those on the line that aren't clinicians, including Bret and Michael, but BRCA1 and 2 give you a big risk and are largely the reason why someone might develop breast cancer. But there's all these other little genetic factors that float around in the background, literally hundreds, if not thousands of them across all of our chromosomes and everything, well beyond BRCA1 and 2, that can give you a little bit increased risk by themselves. And then you can actually add them together into these polygenic, meaning like added together kind of models to figure out someone's risk for breast cancer and other cancers and diseases.
0:41:19.9 S4: Yeah, and I think... Thanks for adding to that TJ, I'm sorry, I glossed over that. I think the way that I like to think of it is the key distinction is the accumulation of these kind of significant single changes in your genome, add them together to get this score and that can contribute to risk. But BRCA1 and 2 that you inherited are the ones that are causing the majority of these cancers that we know about in a hereditary fashion. But the SNP and the polygenic risk score is really a strong area of research that's happening not only in cancer, but in a variety of different diseases and situations like diabetes and others, heart cardiology, for example. So what they did in this study, just to quickly recap it, because it's a pretty beefy paper is in the males, what they found is that the carriers for BRCA1 and 2, they looked at a polygenic risk score that was from 88 for a female breast cancer susceptibility variant. And again, that's what they have to work with, these female breast cancer SNPs, they haven't done research in males to look at those SNPs in males. But they found that it was associated with a higher odds ratio, so a higher probability of getting breast cancer. And then similarly, they looked at about 103 prostate cancer SNPs.
0:42:58.6 S4: What they did is they created different curves to look at the polygenic risk scores that were most informative to stratify the risk for the male carriers for BRCA1 and 2 that could aid in helping make management specific strategies for them. And including timing, when should we screen these individuals younger or later based on their SNP profiling. And this is just a picture of a couple of the curves from the paper. And so I'll just walk you through one, so you can just get a gist. So in figure one, what they did is they broke down the highest and the lowest percentile in the SNPs. And so this is for a BRCA2 carrier. So the risk of breast cancer by age 80, let's just use that as an example, is about 5% for those individuals that have the fifth percentile of the PRS SNPs, so those lower risk SNPs, so it's roughly about 5%, this is in a BRCA2 carrier, so much lower than what we traditionally think. And then in those males that had the higher risk, the 95th percentile, it was the cumulative risk of about 14%. So you can see that's a pretty wide difference in risk, which might result in different medical management, depending on the accumulation of the different SNPs that that individual might have.
0:44:37.2 S4: So, this is just a... I'm not gonna go into the others but it's the same kind of pattern. The point being that if we can look at this population of males that we feel are higher risks because they are carriers, but look at other genomic factors, we might be able to tailor their risk and personalize it, stratify it, so that we can personalize the medical management differently.
0:45:05.3 S1: Yeah. And we're looking at these background factors in the absence of people with BRCA1 and 2 mutations as well, so... Yeah, I think there will be more...
0:45:13.9 S4: Right.
0:45:14.5 S1: More to learn.
0:45:16.0 S4: Yeah and I think that's the... The biggest advantage of this is because when you have somebody like all of you on this call who were tested and did not find an altered gene, what else is contributing to that cancer development? Could it be the SNPs? Accumulation of SNPs, and so for those vast majority of people that test negative from a genetic test, they still might be at higher risk because this accumulation of SNPs and their management might be different than somebody that is... Has a lower risk SNPs than someone that has higher risk SNPs.
0:45:54.5 S1: Yeah and any significant updates to the other genes beyond BRCA1 and 2 like ATM or CHEK2? I know you looked into that as well, PALB2.
0:46:08.4 S4: Yeah. I'm gonna back up here. There's not a lot, basically, in a nutshell, there's been a little bit of work, NCCN when you dig into the back, has some risk figures Yang and all in 2019 for PALB2, they described a risk of male breast cancer 0.9 to 4.9%. Early on in about 2009, this group described with this specific CHEK2 mutation about a 1% risk. This is a figure from Yang and all that looked at the male breast cancer, absolute risk up to age 80, and this Yang and all is from Marc Tischkowitz group. And so... This is a really nice paper because it gives these nice tables and curves for males and females for ovarian, male breast cancer and pancreatic cancer. But the other thing that happened in 2018 was a collaboration with [0:47:12.5] ____ they used cases and controls with the exact study, and they looked at male breast cancer across several genes, more than just what's listed on this table. And you can see the odds ratios for some of these are very significant, and as a result of that, they concluded that males with breast cancer should have a multi-gene panel that includes multiple genes and not just BRCA1 and 2. And that's regardless of age of diagnosis, history, family history or multiple primary cancers.
0:47:53.1 S1: Yeah, thank you.
0:47:54.4 S4: You're welcome.
0:47:55.0 S1: So, questions. Let's see if we can open it back up. I mean, questions for Shelly, or Michael or Bret? And good chat discussion, especially regarding the oncotype paper on male breast cancer patients. I remember seeing that when it came out, and so that's a good reference, if anyone's looking for the use of these kind of gene expression tests in males.
0:48:35.7 S5: You mentioned about a publication, I think Michael you mentioned it. About Cardoso who did something on genomic testing.
0:48:46.5 S2: Dr. Fatima Cardoso?
0:48:49.6 S5: Yeah.
0:48:50.5 S2: I don't have the paper information in front of me, but herself and Dr. Sharon Giordano were doing the largest study up until funding ran dry, and they were making some great headway. Dr. Fatima, she runs an annual meeting in Lisbon. I know someone from the coalition went last year to see what she was presenting, but I don't have that information, unfortunately, you'd have to look that up.
0:49:25.3 S5: It's not published.
0:49:26.4 S2: Yeah. Fatima Cardoso.
0:49:27.8 S5: No, I know her. It's not published yet.
0:49:31.0 S2: Yeah.
0:49:31.6 S5: Okay, thank you, Michael.
0:49:34.1 S2: Yeah, but Bret and I both participated in the CDMRP as peer reviewers in the past, and a lot of people don't realize how much money the Army puts into breast cancer research, but for Bret and I, it was amazing to sit... We were in separate groups, of course, but to sit with the doctors and researchers and to see how passionate they were in looking for a cure or just looking for the next gene in breast cancer research. And it made me feel good to know that there are people out there who have dedicated their lives and are so passionate about this disease. I just wanted to thank you for anybody on this panel who's been submitting stuff for grants through CDMRP. We really appreciate it.
0:50:29.5 S5: Okay. Thank you, Michael.
0:50:37.9 S1: That's great. Any other questions for Bret? Michael? Shelly? Thanks, Elena for posting that other genetic landscape of male breast cancer in the chat, I'll have to look through that. But yeah, I think it's very clear that we have a lot to learn here, and clearly a lot of advocacy as well, so... Will you Bret and Michael, will you both be at San Antonio this year, or?
0:51:12.4 S3: Not in person. I think we were doing everything virtual, if it is, it's always in December. I manage an ice rink at a country club here in Kansas City, so it's very difficult to get away for that. We did go... Mike when was that, 2017 or 2018?
0:51:31.4 S2: Yeah, we've gone... Many of the years unfortunately were virtual.
0:51:35.9 S3: Yeah, I've been able to go. I've been able to go one year, it was definitely a good experience.
0:51:41.4 S1: Yeah, that's great.
0:51:43.3 S2: And I'll be... I'm signed up virtually, but I'm also a member of the Dr. Susan Love research army and there's a possibility that there might be a panel that I can get on, but I think they might be doing that virtually also right now.
0:52:00.6 S1: Yeah, that's great. Well, no, it's much appreciated. It's people like you that really are getting the word out, and I know you were thrusted in it from your own personal experiences, but this is huge. And I'm sure you've helped countless men get through these struggles and help themselves and their family, so hats off. This is a great work. Keep up all the good work here.
0:52:23.0 S5: I would like to make one remark. Often, you have this cancer, you're very concerned, of course "What's gonna happen? Am I gonna get a recurrence metastasis?" Whatever. And then too many times people say, "Well, with the male it's... The chance that you get a recurrence, in long-term, it's much worse, than with a woman" and you don't wanna hear it because it's concerning you very much. But I had recently contact with Professor [0:52:55.2] ____, you know him Ralph? We have... By the way, I've spoken to his secretary today to get an appointment, we saw one in November, you can get an appointment there, and from this professor, he did a lot of research on male, and he said, "Well, if you look in general, the chance of recurrence is a little bit bigger than male, but if you look really at what stages male are, and then you compare the T1s or the T2s or the T3s to woman, then the risk is the same." Only if you talk the total, there are a little bit more male which have these largest tumors. But if you compare the tumor by tumor and the grade by grade, the risk is about the same. And this I thought was very good news to hear from this professor. And he did a lot of research on male breast cancers, but we... I hope we can meet him in November, Ralph.
0:54:03.2 S6: Good-news, thanks.
0:54:04.9 S5: He's changing the laboratory system at the moment so he's very occupied now.
0:54:12.4 S2: And thank you to whoever's posting the PubMeds and this stuff on efficacies of endocrine therapy and Dr. Cardoso's gene expression, you guys are fast on the computer. [chuckle]
0:54:24.0 S1: Yeah, no, that's the benefit of these kind of topics. Lots to unpack in the chat here. The one thing that stands out is just how new a lot of these research studies are, some are just coming out, so clearly there's some focus now turning into male breast cancer when it comes to the background genetics, what Shelly presented, the hereditary risk, thinking about these other oncotype, EndoPredict type gene expression tests that help you figure out if you need chemotherapy. Yes, no, and how aggressive the tumor is so lot to learn, I appreciate though, everyone coming on and thank you so much, Bret, this was great and definitely setting up the foundation, and thank you, Michael, for coming on, this was huge. You guys are both great speakers and Shelly, thank you for showing the slides, even though they are in notes mode, it was okay, just kidding. [laughter] She sent me a side chat that she was embarrassed it was in notes mode. It's alright, notes mode is fine. Thanks everyone. And definitely tune in next week. We will be talking more about the polygenic risk scores, and we'll have Holly Peterson on and ED, and thinking about ways we can really apply these in clinic in 2021 because it is a complicated topic. And Bret, I put also the foundation's website in there, so feel free to...
0:56:03.4 S3: Yes, I saw it. I threw up our breast self exams website as well. So because... All the cards that we have on there, the videos... Anything... If anybody has any questions, feel to reach out. It'll probably get to my mother first, Peggy, who's our director, helps with the communications, but then can just reach out to... She keeps me in check. She's put all these on my calendar, so I don't miss anything, so... Help me out. Help keep me in line.
0:56:29.6 S1: Yeah, no, we will. So yeah, thanks and if anybody listening has... And also this will be on podcast, so if anybody has any opportunities, it sounds like Bret and team have many men that can get on different platforms and help out the cause. Alright, well, thanks everyone.
0:56:49.9 S5: Thank you very much, Thomas for arranging everything.
0:56:51.6 S4: Thank you.
0:56:52.8 S1: And have a good rest of your day.
0:56:52.9 S6: Thank you.
0:56:53.0 S2: Thank you.
0:56:53.2 S3: Thank you, appreciate it.
0:56:53.4 S5: Goodbye.
0:56:55.8 S1: Bye-bye.
0:56:55.9 S2: Bye.
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