Preventing Cancer by Understanding Inherited Risks

Dr. Charles Ryan: This is The Good News About Cancer. I'm Dr. Chuck Ryan. 

Dr. Alicia Morgans: And I'm Dr. Alicia Morgans. 

Chuck: We're oncologists and we've spent our careers working to understand cancer. We believe that there's more progress now in research and treatment than there has ever been. And we're here to share that with you.

Alicia: In each episode of this show, we talk with one of our colleagues about a new development in cancer treatment or diagnosis. We'll break down what's new, why it matters, and how it points the way forward.

Dr. Pamela Munster:  I’ve seen many women walk into my clinic with a big breast cancer that now requires a lot of chemotherapy, a lot of tenure therapy with hormonal interventions, surgeries, and the constant fear of dying of this cancer.  We can prevent this. 

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Alicia: You know, Chuck, when I think about cancer, one of the things that has been a major advance – and one of the things that actually makes me feel a little more informed – is understanding that there are genes that actually are associated with someone inheriting a risk to develop a cancer. And it can be scary to think that there are these genes out there that could put someone at risk. 

But at the same time, if we recognize that fact, and then we investigate, we might be able to understand even when a person is younger, before they ever develop a cancer, that they are at risk and that we need to take steps to screen them and understand how to ensure that we know if they develop cancer or prevent the cancer in the first place. And there are actually a fair number of these genes that we know about and it was really something that's been, I think, an incredible development over the last number of years.

Chuck: Oh yes, there are dozens if not hundreds of genes that are associated with a higher risk of cancer. And we are now, because of the Fruits of the Human Genome Project – which, you know, has been completed now for a couple of decades – we're now getting more and more granular information about what genes are associated with cancer and the risk that they bring.

You know, everybody should know a little bit about their family medical history. When the family gathers at Thanksgiving, or the 4th of July or whenever that is, it's good to understand what it was that Uncle Joe had and what it was that Grandma had because when you go to the doctor and the doctor asks you about your family history, that really matters. Because when patterns come up in our minds as doctors, or we see patterns, we might be able to identify a syndrome, a gene, or something that's associated with some cancers. And that's relevant because now we can test for those, and we can prevent the very cancers that those gene aberrations– that those gene changes can cause.

Alicia: Yeah, I mean, definitely sounds like a great Thanksgiving to talk about all these things. But to your point, this is a way that we can keep the rest of our family safe and well. And you're right that when we're in clinic, if I hear that somebody's grandmother had breast cancer and maybe, their uncle on the same side of the family had prostate cancer and someone else may have had pancreatic cancer, to me, this screams BRCA family. Which is just a specific mutation that's actually relatively common here in the U. S. and around the world that might put somebody at risk, and importantly might change the way we screen young people with those mutations for future cancers and definitely even now already gives people access to medications that target these mutations.

Chuck: But it goes even further than that. Let me tell you a story that I think is just fascinating. So I met a young woman, she's about 30, and her mother had breast cancer when she was in her late 20s, early 30s. So very early onset breast cancer. The mother's doing fine, she's had treatment, but that prompted a discussion of the genes in the family, and testing, and this family was found to have a mutation in the BRCA1 gene, or we call it BRCA.

And because of that finding, the woman I talked to, who's 30 years old, went and had herself tested when she was in college, I think it was, and she's a carrier. So, she has to watch, you know, mammograms and, and there's, there's treatments she may undergo to prevent cancer of the breasts and of the ovary and other things. And those are now preventable because she has that knowledge. 

But: taking it one step further, she's now about to have children. In fact, she already has had her first child. And what they were able to do is, they were able to do in vitro fertilization, and they were able to select the embryo that did not carry the mutation. Half the embryos carry it, half the embryos don't. And so by doing that, she removes that mutated gene from her gene pool. She removes it from the family bloodline forever. 

And there is epidemiological research now that can trace a particular mutation in BRCA1 or BRCA2, any of these genes. And they can literally go back in time by looking at human migration patterns and identify how long ago this mutation occurred. 

At some point in history, there was a person who developed this mutation. This gene just spontaneously mutated. And that person went on to have children, and they went on to have children, and generations and generations. So this young woman I was speaking to, she's of Polish descent, and the gene that she carries was first identified in Poland, they think, around the year 990.

So that is over a thousand years of a family having cancer over and over and over again. And when you think about our ancestors in the last 1,000 years, if you carry that gene where over 50% of the people who carry the gene will get a cancer, think of all of the young deaths that have occurred throughout all of the centuries in that family. And now, in 2025, she puts an end to that. Forever. 

And that, honestly, that story was one of the things that prompted me to start this podcast. Which is, that is an incredible story that is ending a thousand years of cancer. If that's not good news, I don't know what is.

Alicia: Ending a thousand years of cancer is an incredible feat. That is definitely something that I would agree is amazing news. It goes beyond good news and really gives hope to everybody out there to think about further understanding what is driving an individual's cancer so that we can take that risk away in the future hopefully for everyone else in their family and eventually maybe take it away entirely at least the things that we inherit.

Chuck: Part of the advantage of identifying these genes that can cause various cancers is that it has enabled the development of specialty clinics that are focused solely on the various manifestations of cancer that arise from these mutations.

One of the first such clinics opened up at the University of California, San Francisco, where I used to work. And was started by Dr. Pamela Munster, who's a longtime colleague and friend of mine. Dr. Munster is interesting because she started this clinic, she's a breast cancer specialist herself, and she's a BRCA carrier and a breast cancer survivor herself.

So there's really a very unique set of circumstances in her life that has led her to be a real spokesperson for this challenge. So here's our conversation with Dr. Pamela Munster of UCSF's Helen Diller Family Comprehensive Cancer Center. 

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Chuck: Dr. Pamela Munster, welcome. You have a good news story, I think, and you're part of a good news story that I'm excited to talk about today. We're going to talk about BRCA, and there's BRCA1 and there's BRCA2. But for those who don't know what that means, tell us what that is.

Dr. Pamela Munster: If someone is born with a BRCA mutation, and more recently, the term mutation was changed to variant. So when you hear me talk about mutation or variant, they're both interchangeable, but the newer term is variant. 

What happens is these individuals, both men and women, are then at high risk of developing cancer. And not just developing cancer, but really developing cancer at the lower end age of their lives. 

So a BRCA1 or a BRCA2 variant in a woman can put this woman at risk for almost 60 to 80% of lifetime risk of breast cancer. Another very high risk cancer is ovarian cancer. A patient with a BRCA1 mutation has a 20 to 40% lifetime risk of developing ovarian cancer. 

For BRCA2, there's a little bit lower risk of ovarian cancer. Other risk factors are pancreatic cancer. The risk for pancreatic cancer happens in both men and women. BRCA stands for breast cancer gene, but it has huge implications for men and the implications are for prostate cancer. The newer data suggests that a man with a BRCA2 mutation can have up to 60% risk of having prostate cancer. 

Chuck: How common are these? You know, are these rare mutations that only occur in a select number of people or, you know, if we go to a party and there's a hundred people there, how many of them are carrying a BRCA gene, mutation, variant?

Pamela: So depending on what population we're talking about, it's like we think the BRCA gene can be as high as 1 in 50 the Ashkenazi Jewish population. It's probably closer to 1 in 100, 1 in 200 in the general population. 

But it's not just BRCA1 and BRCA2, there’s ATM and CHEK2, there's PALB2, there's BRCA1 or 2. That pathway has a lot of, uh, mutations around it, that pathway that can be also mutated. So taking all together, we are almost looking at two to three percent of the population. 

So in your party of a hundred, a good two to three percent of the people there could be born with a mutation that puts them at high risk for a cancer that we completely prevent and they don't know about it.

Chuck: Right, right. So there's two elements there. The prevention, which can take place, but you can't prevent something if you, really, if you don't, you don't know about it.

Pamela: You know, Chuck, I have seen many women walk into my clinic with a big breast cancer that now requires a lot of chemotherapy, a lot of tenure therapy with hormonal interventions, surgeries, and the constant fear of dying of this cancer. 

Similarly, patients present in their late, late thirties, early forties with ovarian cancer, and they spend the rest of their lives on chemotherapy. We can prevent this. 

I'm really hoping – and that was really main focus on why I created the hereditary cancer clinic, that's multidisciplinary and comprehensive – if someone knows that they have a risk of ovarian cancer and once they're done with childbearing and take the ovaries out, we can pretty much replace all hormones that the ovaries functions. We can store fertilized eggs. So we can take the ovaries out and reduce the risk for fatal cancer in a young woman

Chuck: And that's been proven.

Pamela: Yeah, I mean, without massively compromising her quality of life. And, you know, as an oncologist, every life you save is an important part of what you do.

Chuck: Absolutely. And this is something that women should do after they've done their childbearing. It's not something where they should say, “Oh, I have a BRCA mutation. I should– I should not have children. And I should get my ovaries taken out while I'm still in my 20s.”

Pamela: Let's say you're 31 and you recently found out that you have a BRCA2 variant. What are the next steps, right? So in a typical consultation, we would ask, what's your plan for child rearing? Do you want to have another child? And that 32 year old says, like, “Yeah, I really want to have another child. I'm not quite ready. I'd like to push it back to 35. Can I wait that long?”

And, and we go like, “Yes, we, we just have to be, we, we follow people along very carefully.”  Right. And then, so we let the woman have her child. And then if she's 36 and says like, you know, “I'm really done now, my family has ovarian cancer. So my grandmother died of ovarian cancer at 45.” Then we probably feel more compelled to take the ovaries out then. If someone is really, really worried about going into menopause, there's no family history of ovarian cancer, we wait a little longer.

I, you know, having a BRCA2 mutation myself, what I really realized when I was diagnosed with a BRCA variant, is that it was really difficult to find the physician who could address a lot of my questions. So when do I take my ovaries out? What is my pancreatic cancer screening? And when I was diagnosed, 13 years ago, pancreatic screening was not an issue.

So I think over that time, like from year to year, we have new guidelines. We have new data on hormone replacement therapy. So I think it's, it's both an incredibly rich opportunity for us to do research, but also have updated recommendations.

Chuck: But this isn't, just making the point, this isn't, we think it will prevent cancer and prevent you from dying of cancer. We know this. There have been studies that have shown, right, that if you do these things, take out your ovaries, prophylactic mastectomy, correct? I think your likelihood of dying goes down. It's a proven intervention. 

And clinics like yours, as far as I know, one of the first ever in the country completely devoted to this population. There are others out there now doing it, for, you know, many parts of the world. But, it creates a space where one can go and get all those questions answered. 

And, to some degree, it takes the burden off of, the primary care physician, the family doctor, of having to understand, this and it helps them, I think, know what to do if they confront a patient with a significant family history of cancer who wants to do something preventative or who wants to do something proactive about reducing the risk.

Pamela: And I think an important part is to really go back. If you’re born with the BRCA1 or BRCA2 variant, you're not born with a cancer, you are born with the risk of a cancer. The likelihood that the mutation is passed on is 50 percent in your offsprings and it's very important to mention this can be towards a boy and towards a girl. This is not a female mutation. The cancers are not specific for females. The mutations are not specific for females. It is not a mutation that's only obtained from the mother. Like I got mine from the father.And if I may add something, it's like what I have learned as a clinician is like, you know, the healthcare system is overwhelming on a good day.

I guess it's really overwhelming to deal as a patient with the healthcare system. And it is not trivial to schedule a pancreatic MRI or a colonoscopy. And if you're just told that you're at risk for pancreatic cancer, like you should get pancreatic cancer screening, where do you even start? But I think the important part of the clinic is like, when we help people schedule their tests, their imaging, their tests, their follow up, we found in an early study that we did is we found that 85% of people complied with their recommended screening within a month of planned screening tests. And I think this is quite amazing

Chuck: So, I have to acknowledge, you and this work, and this clinic, and these drugs, and this testing, all sort of happened about a decade ago. And it was around this time that you yourself found out that you are a carrier. And you went through your own series of treatments and you and your family–  tell us a little bit about that and and it was it your personal journey that inspired you to start all of this? Or were you already kind of going down this path before you had your own personal issues?

Pamela: I've always dabbled with BRCA. I've seen a lot of patients with BRCA mutations and seen a lot of young cancer, we have been testing patients. So, BRCA has always been part of my research and it's always been part of my practice. 

And never ever would have thought I would be a BRCA1 carrier. In fact, when I had breast cancer and I said, I want to have a BRCA testing, it was very clear I wasn't even meeting criteria. That was in 2012. I wasn't quite meeting criteria because there was nothing in my family history or in my makeup that would suggest that I have a BRCA mutation.

I think that's what really drove it home is like, my husband thought I was so unlikely that I should not be tested. My genetic counselor thought it was very unlikely and then everyone goes like, “Oh darn, you have a BRCA2 mutation.” 

I had to go through breast surgery. Then I had to find myself someone who takes care of my ovaries, and then I had to figure out what to do with my kids, and when do I test my kids. And I just felt like it's really difficult to get those answers. And then I thought like I'm an oncologist, and have all these incredible friends they're all also oncologists and they're surgeons, and I have so many people and it was very easy for me to knock on my friends’ and colleagues, doors and get answers. But I thought like, how hard must this be for someone else?

Chuck: You have all that expertise, all that knowledge, you’re literally one of the most intelligent oncologists on the planet, and you have to navigate all of this yourself, and you’re saying: we should have a one-stop shop for this. So you built it.

Pamela: I think one of the most important parts of having such a clinic. And I think this what, what really differentiates, you know, healthcare is like, if you find a lump on your neck in the middle of the night, you need to have that one number that you can call and find out, is that real or not real?

I think in medicine, it's like– the one thing that I remember from having a breast cancer is how lonely I felt. How just completely lonely I felt with like, who do I talk to? And I think, what we're really hoping is to create this: you're never out there alone. There's always someone there who can answer a phone call and can answer a question.

Chuck: So that’s great if you live in the Bay Area and you can come in to see you and go to your clinic, but what if you don't? What about people who don't have that kind of access close by?

Pamela:  Chuck, you're asking me what am I doing in my next 10 years? And I think I'm really hoping that we can build this out, that this becomes available, in more areas. So right now a big part of what I'm trying to do over the next few years is really creating a wider network of having such clinics that are dedicated for patients without cancer, but carrying a risk for cancers or hereditary cancer clinics that are specifically dedicated for this.

Chuck: Well, Pamela Munster, a longtime friend and colleague, and I've admired your work, and you personally, for a long time. And it's really great to chat with you about all the wonderful things that you're doing.

We actually could talk about many of the other wonderful things you do, like starting a company and, all these other, great things. But, thank you so much for joining us today and to talk about your own personal journey and how you're making that personal work apply to people who will benefit from your work, and from your knowledge, for years to come. So thank you.

Pamela: Thank you. It's always a pleasure talking to you. And as you know, like, you've been very instrumental in some of the work I do, so 

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Alicia: Well, that was great. And I have to say, I am still thinking about your comments about really ending a thousand years of heritable cancers in a family. It's just an incredible concept and really such a wonderful conversation with Dr. Munster.

You know, one thing I, I do want to make listeners aware of, you know, Dr. Munster has a book. It came out a few years ago. It's called Twisting Fate, My Journey with BRCA: From Breast CancerDoctor to Patient and Back. And it's a really powerful story and includes some of the things that she touched on today in her conversation with you.

Chuck: Yeah, it's a great read, and I really enjoyed the conversation I was able to have with Pam, a long time friend, and, and she's always been an inspiration to me. 

So thanks for listening to The Good News About Cancer. I'm Dr. Chuck Ryan at Memorial Sloan Kettering Cancer Center in New York.

Alicia: And I’m Dr. Alicia Morgans at Dana Farber Cancer Institute in Boston.

Chuck: Thanks to Lilly for support of the show. Our production partner for this series is CitizenRacecar. This episode was produced by Anna Van Dine with post production by Alex Brouwer. 

Alicia: And there's a whole lot more good news to talk about. So make sure you subscribe to this wherever you listen to podcasts. 

And if you like the show, share it with someone you think might find it interesting.

Chuck: We'll be back again soon with more good news about cancer.