Understanding the Genetics of Breast Cancer

On this week’s episode of Cancer Care Connections, Cheryl Tan discusses with Dr. Sonia Hepburn, hematologist oncologist for Virginia Oncology Associates, the pros and cons of genetic testing, specifically as it relates to breast cancer and other associated cancers.  

 Dr. Sonia Hepburn received her Bachelor of Science in Molecular Biology from Princeton University. She received her medical degree from the University of Southern California where she also did her internship/residency in Internal Medicine. She completed her Hematology/Oncology fellowship at the University of North Carolina - Chapel Hill.  

She is an active member of the American Society of Clinical Oncology and the American Society of Hematology. She is trained in treating all cancer types with a special interest in breast, lung, and gastrointestinal cancers. 

Topics
What is a genetic mutation? [2:22]
Recommendations for a breast cancer patient to undergo genetic testing [3:41]
What is the genetic testing process? [6:49]
What the test results mean for patients with breast cancer [ 7:25]
Family history and the Tyrer-Cuzick model score [9:39]
Variations in cancer risk based on mutations [10:58]
What does it mean if the test comes back negative [13:17]
Patient Story – predisposition to cancer [16:20]
How to get referred [18:24]


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Cancer Care Connections is the official podcast of Virginia Oncology Associates. For more information, visit us at VirginiaCancer.com. or find us on Facebook or Instagram at Virginia Oncology Associates.

Transcript

00;00;00;00 - 00;00;30;02
[Introduction with Music Overlay]
Welcome to Cancer Care Connections. On this episode, Cheryl Tan spoke with Dr. Sonia Hepburn, hematologist oncologist for Virginia Oncology Associates. Cheryl and Dr. Hepburn dove into the pros and cons of genetic testing, specifically as it relates to breast cancer and other associated cancers.

00;00;30;05 - 00;01;01;07
Cheryl
We're diving into a subject that gets quite a bit of interest from patients and their families. Genetic testing. Today we're specifically talking about genetic testing and breast cancer. We are happy to have Dr. Sonia Hepburn here with us. She joined Virginia Oncology Associates in 2020. She's trained in treating all cancer types with a special interest in breast, lung, and gastrointestinal cancers.

She's a physician champion for genetics on the peninsula. Dr. Hepburn, thanks so much for joining us today.

00;01;01;07 - 00;01;02;10
Dr. Hepburn
Thank you for having me.

00;01;02;11 - 00;01;18;03
Cheryl
Thrilled to talk with you about this topic that I know gets a lot of interest, and a lot of questions here at Virginia Oncology Associates. I want to start, though, by asking how you ended up here in Virginia, your path to here, and how you like it.

00;01;18;05 - 00;01;36;21
Dr. Hepburn
Sure. So I think I've been kind of going back and forth between different coasts. But most recently I was at UNC and doing my fellowship there and my husband's family is from Virginia, so when we were looking at places to potentially start a family and locate, we were very much looking into VOA.

00;01;36;24 - 00;01;39;04
Cheryl
Congratulations, by the way, on your little girl.

00;01;39;05 - 00;01;40;16
Dr. Hepburn
Yes, Thank you very much.

00;01;40;22 - 00;01;45;27
Cheryl
And as far as genetic testing, that topic, that is close to your heart.

00;01;45;29 - 00;02;04;06
Dr. Hepburn
Yes, absolutely. I see many, many cancer patients. And I think that's one of the things that not only do we want to treat them, but they always come in and say, okay, I have cancer, but what impact does this have on my family? What can I do to protect them best? And so I think it's a very important topic to talk to the patients and their families about.

00;02;04;13 - 00;02;07;17
Cheryl
It's a holistic way to treat your patients.

00;02;07;19 - 00;02;08;08
Dr. Hepburn
That's exactly right.

00;02;08;08 - 00;02;22;21
Cheryl
Let's let's kind of get some definitions out there. What exactly is genetic testing and what should that mean for someone who's been diagnosed or someone who has a family member who has been diagnosed with, in this case, breast cancer?

00;02;22;23 - 00;02;51;29
Dr. Hepburn
Sure. So genetic testing means that someone was born with a specific change or a mutation that then predisposes them to have breast cancer or colon cancer or any type of cancer risk. It tells us that they have a high likelihood and that we should be doing screening. But in particular, for those breast cancer patients that already have a diagnosis, it has implications on how we treat them.

So we do talk about it in depth when they get diagnosed to then determine how are we going to treat them going forward.

00;02;52;04 - 00;03;01;08
Cheryl
And then, of course, it means something for their children, maybe their sisters, other relatives, blood relatives. 

00;03;01;08 - 00;03;20;24
Dr. Hepburn
Right. So if they test positive, oftentimes these mutations or changes are carried on. There's a there they're called autosomal dominant, meaning that there is a 50% chance that they could then pass that on to their children. And so for that reason is why this has high-impact and we want to know about it up front.

00;03;21;00 - 00;03;41;22
Cheryl
Okay. Let's talk about sort of the recommendations that you have. What is the recommendation for a breast cancer patient to undergo genetic testing? At what point do they say, well, my mom, my sister, my grandmother...At what point should they be thinking that this is something that they should be thinking about for themselves?

00;03;41;27 - 00;06;34;20
Dr. Hepburn
So when someone gets initially diagnosed, they usually get to see different doctors that are going to take part in their care: the surgical oncologist, the medical oncologist, radiation oncologist. It's our very first meeting with the medical oncologist that we start talking about their family history. So that's when we start gauging...I think just having a specific type of breast cancer qualifies them for testing and then also family history.

So I'd like to get into that a little bit. So we follow something called NCCN guidelines. It stands for National Comprehensive Cancer Network guidelines, and those are the guidelines that have been set forth for all of us to follow to see whether someone qualifies for genetic testing. And I'll talk specifically for breast cancer. So with breast cancer, any person that's been diagnosed with breast cancer before the age of 50 automatically qualifies because the earlier they get diagnosed, the more likely they are to have a breast cancer mutation that we talk about.

Strictly speaking, it's about 10 to 15% of people that get diagnosed with breast cancer that do have a mutation. So it's not high, but it's a very good sizable amount. And especially if they get diagnosed before the age of 50, it makes us think that there might be something there that predisposes them to have such early-stage breast cancer.

Other breast cancers that we automatically test; anyone with triple-negative breast cancer, regardless of their age gets tested, any male with breast cancer automatically gets tested, and anyone who has Ashkenazi Jewish descent gets tested. Outside of that, if their age is over 50, they don't meet the criteria that I just mentioned, other things that usually also get involved are like family history of cancers.

And so that's where it's going to be very important to know a little bit about that information at our first visit. So for family history, some of the basic broad overview would be anybody that had a first-degree family member that had these cancers. And so by first-degree, I mean parents, siblings, children, those are all first-degree family members.

Second-degree also counts. Those tend to be aunts, uncles, grandparents. And so it would be someone who had early cancers before the age of 50 or if they have other cancers that tend to correlate with breast cancers such as ovarian, colon, prostate, pancreas, and melanoma, also kind of go hand in hand. And so it seems like a lot of criteria, but that's why we usually start talking about it at the beginning and it's something that we addressed over time.

But I think it's important enough to try to understand it, especially because some of those genetic test results can have implications for surgical outcomes afterward.

00;06;34;23 - 00;06;48;25
Cheryl
Can you discuss what the testing is like, what that process is like? Because I'm having trouble sort of figuring out in my head what that means. And I can only imagine when someone gets the news what is going through their head.

00;06;49;03 - 00;07;15;09
Dr. Hepburn
Right. So it's actually a pretty simple test to do. So it's either a blood test that they just automatically give that same day or it's a saliva test kit that they get mailed out that they could just swab their cheek and then mail that. And generally takes longer to do the swab. It's faster to do the blood just because of logistical purposes, but both of them give us the same information that we want the DNA to be able to check for those mutations.

00;07;15;17 - 00;07;17;14
Cheryl
And then that can be done here, for example.

00;07;17;14 - 00;07;19;16
Dr. Hepburn
Yes, it can be done in the clinic, the same day.

00;07;19;19 - 00;07;25;17
Cheryl
All right. And then this sample is sent out, evaluated, and then what happens next?

00;07;25;18 - 00;08;31;16
Dr. Hepburn
So depending on how quickly we need to know...so for some people, we know that they have very early-stage breast cancers, and they want to move on to something like a lumpectomy. But if they were to have a BRCA mutation, the BRCA gene, specifically one and two; that increases their risk for breast cancer. And it's with those genes specifically that we then recommend a bilateral mastectomy.

So for those people that have; they're young at age when they're diagnosed, and we know that it could potentially mean having bilateral mastectomy if they were to have a BRCA mutation, we try to send it as STAT testing. That turnaround time can come back within seven business days, so we can have that information before they make their decision on the type of surgery that they're going to have.

But in general, for standard population, for most people, it takes about 4 to 6 weeks to get a long, big, comprehensive test. With that STAT testing, it just gives us BRCA one and two, which is the main one we want to know about. But then if we want the broader panel, it does take some time so that they do thorough testing.

00;08;31;19 - 00;08;45;29
Cheryl
So in some cases, the results of this test really determine the kind of care, the kind of treatment a patient gets. But in general, what does this information do for a patient? How does it help you, help them?

00;08;46;03 - 00;09;16;22
Dr. Hepburn
Well, so as I mentioned before, with the surgery part, it helps. But it also helps, for instance, triple-negative breast cancer patients who have a higher likelihood of having that BRCA mutation. And down the line, it means that if they're more high risk of this coming out; of their cancer coming back or they're more advanced stage, a PARP inhibitor is a specific drug that works in patients that have that BRCA mutation, so it means we have alternative options for treatment for those patients as well.

00;09;16;24 - 00;09;39;06
Cheryl
You've just shared so much information and it's helpful, I think, to sort of break that down. So I really, I appreciate you doing that. Do you often have or do you ever have people come to you who don't have cancer but may have a significant family history of cancer and they say, please test me? Does that ever happen?

00;09;39;07 - 00;10;41;06
Dr. Hepburn
Yes, it happens all the time. And so that's because everyone has...it seems like I think in general, more and more people are having family members or friends or something that they're just concerned about having the mutation and they really want to know. And oftentimes..so now the recommendation for breast cancer patients is to start screening at age 40.

And for most centers, actually, now, they start asking about family history to calculate something called a Tyrer-Cuzick model score. So it takes into account that family history. So it says, what's the likelihood of you having a lifetime risk of breast cancer? And if it's greater than 20%, then they get referred to me just because they have a strong family history. So even if they don't have the genetic change, it still means we need to do increased screening for them. And so that's often how I end up seeing patients; is that they are considered high-risk. And then we talk about their family history and then we do the genetic testing to see do they actually carry the mutation and talk about their risk overall.

00;10;41;08 - 00;10;47;09
Cheryl
And then there's counseling that goes in that especially since they have not been diagnosed yet.

00;10;47;12 - 00;10;58;11
Dr. Hepburn
Right. So we need to talk about the implications of the genetic testing, what it means for them, the possible limitation, and if there's any drawbacks to doing the genetic testing as well.

00;10;58;14 - 00;11;04;18
Cheryl
I want to ask about variations in cancer risk based on the mutations.

00;11;04;20 - 00;13;01;05
Dr. Hepburn
Yes. So I think I alluded to it a little bit early on where the BRCA mutation has the highest risk. So standard risk for breast cancer in the population is about 10 to 12%. With BRCA mutations, it increases by up to 60 to 80%. So oftentimes we think it's not a matter of if they're going to get breast cancer, it's when they're going to get breast cancer. And unfortunately for that reason is why with people with those mutations, we often recommend bilateral mastectomy. And sometimes it's individualized, too, because sometimes people find out that they have this early on, but they still want to have children, for instance, they want to breastfeed and all of that. And so we do counsel them as to when the best time is to go ahead and do that.

00;11;47;01 - 00;12;15;06
Dr. Hepburn
But then we also talk about other things they could do for screening, like alternating between MRI and mammogram every six months. Luckily, we have good screening methods for breast cancer where we could do that and feel comfortable being able to catch something early if we need to. Other mutations that we often test for that also have implications for breast cancer are something like CHEK2, PALB2, those carry more of a 30 to 40% risk of breast cancer.

And although it's higher than the 12% that's in the population, it's not the 60 to 80 that BRCA has. And so for those patients, we say, yes, you have a higher risk, but we generally recommend screening imaging as opposed to bilateral mastectomy in those cases. And the important part about knowing these mutations is that, yes, I think we focus on it for the breast cancer diagnosis when someone's diagnosed initially, but as I mentioned, some of these mutations carry implications for other cancers as well. And so it's important to know that we need to screen for those other cancers as well at an appropriate rate once they've kind of gone through all of their breast cancer treatment, then we step back and say, okay, so how do we prevent from having ovarian cancer or colon cancer or other things that they might be at risk for as well?

00;13;01;08 - 00;13;07;03
Cheryl
So these test results could mean many things that you're not necessarily prepared for.

00;13;07;05 - 00;13;17;14
Dr. Hepburn
Right. Right. So that's the importance of talking to somebody who understands the implications of these genetic results and talk about them ahead of time before going forward with the testing.

00;13;17;16 - 00;13;23;18
Cheryl
What is a test comes back negative? Is that a clear sign that there is no cancer present?

00;13;23;20 - 00;15;27;17
Dr. Hepburn
So it's a great question. So I think that the more we're doing with genetics, the more people we're testing, the more information we have. And so we know that it's not perfect. As I mentioned before, we rely heavily on someone's ability to tell us their family history. Sometimes that exists, sometimes it doesn't. And so I think that it's still right now we put 10 to 15% of people have some sort of a genetic risk, But it's possible that we're underestimating it because we just don't know, we're not testing everybody. And so one of the things that is, so if it's negative, it may be that we potentially just don't have a gene that we know of that is going to actually be present, but we just can't tell the risk. For instance, some lung cancer patients that are non-smokers, sometimes it does run in families and we know that happens, but for some reason we don't have a specific gene that correlates that yet. And so we know that some of these things exist. And even with breast cancer before 2013, they weren't checking the CHEK2, PALB2 mutations that we know of now. So anyone that had genetic testing back before 2013 we're retesting, because now we have more genes that we're adding to it.

And even within the BRCA genes there are so many mutations within the BRCA gene pool that we're testing more and more and we're finding more. Oftentimes, one of the things that comes up a lot is that patients get tested and they get this variant of undetermined significance. But what do I do with that? 

Cheryl
Right. 

Dr. Hepburn
So they have this mutation. We don't know what it means. As of now, we generally say we treat it as if it's benign. We know that this is in the background. But the nice thing about doing genetic testing with big companies that have these large databases is that they'll keep the names in the file. And so if by chance, after certain years, they start to see a pattern where these people have this change and they actually do go on to develop different cancers, they can then change that to a pathogenic risk and that'll alert everybody as well.

00;15;27;21 - 00;15;51;08
Cheryl
What is your message to patients as they're listening to this? I'm sure with interest and maybe there's a personal reason that this genetic testing is so close to their heart, as with you. What is your message to them as they're listening to all of this, all the changes, all the positive changes in research and technology? But I mean, what do you say to them?

00;15;51;11 - 00;16;08;21
Dr. Hepburn
Sure. I feel like it could be a bit overwhelming. But so much information, so much to keep track of. But it's an exciting time. I really do think that there are so many different ways to get tested, and I really think that being proactive is going to be the best way to keep themselves and their family as healthy as can be.

00;16;08;26 - 00;16;20;14
Cheryl
I know that you took a special interest in genetic testing because of the work you do with breast cancer patients. How have you seen that come full circle for you as you treat patients?

00;16;20;17 - 00;17;40;17
Dr. Hepburn
I think that it has allowed us to, as I mentioned before, I mean, we have these patients that have these breast cancers and then in checking for them to see whether they are predisposed to their cancers, we do the screening and have found early cancers that we're able to intervene on. So there is a patient of mine who had a BRCA mutation. We were very focused on the breast cancer, of course, at first. And then as time went on, a couple of months in, we said, okay, let's start to focus on screening for other things. She didn't have a full family history, so we said, okay, you are predisposed to pancreatic cancer. Let's go ahead and do one of the ERCPs.

So it's a specialized test to check for that. And they found a small cyst that actually was cancerous. And so it was found at a very, very early stage where all she needed was surgery. It got taken care of and that was the best things because we were able to help her because, otherwise, as you know, pancreatic cancer carries a very poor prognosis.

So it's something that we were able to help her and then she was able to then tell other family members, hey, get checked out. It's an easy test. We're able to do it. And the nice thing is a lot of these companies want family members to get tested as well. It helps their databases. And so for the most part, in most places, if a family member tests positive, other first-degree family members can test for free within the first 90 days.

And because it's something that as long as they're in the U.S., as long as they're above the age of 18, they're able to do it. And they can do that because they could do that saliva test kit. They mail it out and they mail it back. And it's easy to do. So it's a great way to be informed, be proactive, and really try to keep people healthy.

00;17;57;23 - 00;18;24;02
Cheryl
You're telling me that story and I'm getting chills. And you really understand that knowledge is power in this case and that you having that knowledge really help this patient when maybe years down the road it may not have been possible. 

Dr. Hepburn
Maybe. That's right. 

Cheryl
Wow. Thank you so much. Anything you'd like to say, I guess, as we wrap up this episode. And yes, there's a lot that happened here. 

Dr. Hepburn
Yes

Cheryl
Maybe you need to rewind this. Go from the beginning.

00;18;24;02 - 00;18;55;19
Dr. Hepburn
I guess. But how do we even get to this point? How do you get referred? How is it that you get in touch with us? So I think that generally, oftentimes the way that it's done, if someone doesn't have a cancer mutation or a cancer diagnosis, it's usually something that they go to their PCP. They say, "I have this in my history. I'm interested in talking to a genetic counselor" and being referred, and that's how that starts. So I think go to the PCP saying, you know, I have a family history that's concerning me. I'd like to get tested. And then they get referred and we'd be happy to see them at VOA.

00;18;55;24 - 00;19;07;11
Cheryl
And, what I'm hearing, too, is it really is up to the patient to take control. Something in their family makes them realize, oh, I need to do something. And then this really starts with them.

00;19;07;13 - 00;19;16;14
Dr. Hepburn
Right? Right. Being proactive goes a long way. And yes, absolutely. I think it starts with them going to their PCP, having that referral, and then we'd be happy to take over from there.

00;19;16;15 - 00;19;20;05
Cheryl
Dr. Hepburn, thank you so much. Thanks for sharing your wisdom with us today.

00;19;20;08 - 00;19;25;04
Dr. Hepburn
Sure. Thank you for having me.

00;19;25;07 - 00;20;24;13
[Exit with music overlay]
That's all for this episode of Cancer Care Connections. Stay tuned for our next episode, where Cheryl will speak with Dr. Mark Fleming about the importance of prostate cancer screening, especially for those with an increased risk. He also discusses the advancement of treatment options available at VOA through participation in clinical trials and continued research. 

Don't forget to subscribe to our podcast via Apple Podcasts, Spotify or anywhere podcasts are available, or listen online at cancercareconnection.buzzsprout.com. Cancer Care Connections is the official podcast of Virginia Oncology Associates. For more information, visit us at VirginiaCancer.com or find us on Facebook or Instagram at Virginia Oncology Associates.