Genetic Testing for Breast Cancer

John Horton:

Hello, and welcome to another Health Essentials Podcast. I'm John Horton, your host.

When it comes to breast cancer, most of us are familiar with the basics about screenings and warning signs, but genetic testing can add another layer to that conversation. It's a tool that can offer important information about your cancer risk so that you can chart a path to better protect your health.

But what exactly do these tests look for, and what does it mean if a genetic mutation is found? I'm going to talk through that today with Dr. Lakshmi Khatri, Director of Cleveland Clinic's Medical Breast Center. She is one of the many experts at Cleveland Clinic who join us weekly to answer important health questions.

So with that, let's find out what we can learn from genetic testing for breast cancer, and more importantly, how we can put that knowledge to use.

Welcome to the podcast, Dr. Khatri. We appreciate you stopping by to chat about genetic testing for breast cancer. It is such an important topic, and one that's, I know, often misunderstood. I'm hoping our conversation answers a lot of questions for folks.

Dr. Lakshmi Khatri:

John, thanks for having me.

John Horton:

Well, let's start with the very basics because that always seems like a good place to start. So what does genetic testing for breast cancer actually look for? I know a lot of people may have heard about the BRCA gene, but it's much more than that, correct?

Dr. Lakshmi Khatri:

That's right. So when we are looking for a genetic reason for breast cancer, what we're looking for are a number of different variations in a gene that could lead to the development or predisposition to breast cancer, but also other cancers as well. So often, when people are getting this type of testing done, we're actually testing for many different genes, not just associated with breast cancer.

John Horton:

Well, and I think you told us it was like 12 or 13 gene variants that you look for.

Dr. Lakshmi Khatri:

Yeah. So specifically, gene variations that can increase your risk for breast cancer, there's 13 of them, although some of them are quite rare. And there are some, as you mentioned, the BRCA gene, that a lot of people describe as the BRCA gene, there's actually two of those genes that we have and they're much more commonly seen and we just have a lot more information about those.

John Horton:

Yeah. And these are all genes that we all have, right? But it's just you're looking for, I guess, there's a variation or a mutation with them that somehow means they don't quite cooperate the way you want them to.

Dr. Lakshmi Khatri:

Yeah. So what these genes really are, are instructions. So they're sets of DNA in our body. They are instructions that tell our body how to function, and particularly, the ones that are associated with cancer risk are ones that are helping our cells repair on a daily basis.

So there is damage that is happening to our cells in our body all the time. And we have these built-in genes that are, again, instructions that tell our cells how to repair themselves, how to not overgrow. And if cells are growing out of control, instructions to stop those cells from growing.

So if you have a mutation or a variant, we call it a pathogenic variant, because variants in genes are common, right? Our bodies are all very different and having variations in genes doesn't mean there's a problem, but there are pathogenic or disease-causing variants that would basically lead us to have a broken repair mechanism in our body and that could predispose us to certain diseases. And in our case, it's breast cancer or other tumors.

John Horton:

Yeah. It sounds like we basically have this repair process that's kind of built into us, but when you have this mutation, you sort of have a gap in that system.

Dr. Lakshmi Khatri:

Yeah, exactly. So you're just not always able to repair cells when they're being damaged. Now, this isn't all or nothing. It's some of the time. So if you have a variation in one of these genes that we consider pathogenic, it doesn't mean you're going to get cancer. It just may mean that you are more likely to get cancer. And depending on the gene, we're able to understand what that level of risk looks like.

John Horton:

Now, you mentioned that there were 13 gene mutations that these genetic tests will look for. Why is it then that BRCA1 and BRCA2 seem to get so much attention?

Dr. Lakshmi Khatri:

Yeah, so they are more commonly seen in certain populations, specifically, about, in the general population, it's something to the order of 1:400 people will carry one of these mutations. And actually, in people with Ashkenazi ancestry, it's about 1:40, so the risk is much higher there. And I think the other reason we think about it a lot is because Angelina Jolie, who's a famous actress, had come out about her BRCA gene mutation, and forgive me, I'm not sure which one she carries, but there was a big article that came out in Time magazine many years ago about her genetic variant and how she managed that risk. And so I think it became much more common in the general public to understand what these are.

John Horton:

Yeah. It's amazing what a little social attention does for some of these sorts of health conditions. People do start paying a little more attention.

All right, so you do one of these tests and you get these results back and it shows that you have a mutation or a variation. What does that mean to you? Is that something then you should look at it, that cancer is kind of inevitable in your future?

Dr. Lakshmi Khatri:

Yeah. You know, John, it really depends. It's a great question because it really depends on which pathogenic variant or which gene mutation you find. We have a lot of information, a lot of studies that are done on populations of people who carry these genes, and so we kind of understand what the level of risk can be. But these are sort of averages, and when I'm talking to somebody in front of me about one of these gene mutations, I want to make sure that when I'm giving them numbers for level of risk, that they understand that that level of risk applies to a population of people that were studied and they're an individual, and sometimes it's hard to completely individualize those conversations. So it's important to know that these numbers are general risks and they're not always the exact risk that you might have.

John Horton:

What is that risk number? I know we talked ... it can be extremely high for some of these variants.

Dr. Lakshmi Khatri:

Yeah. So I think a nice way to talk about that risk is to compare it to the average woman. So the average woman in the U.S. has a lifetime risk of about 12 to 13% chance that she's going to get breast cancer. So unfortunately, it's very, very common.

John Horton:

That's 1 in 8. I mean, that just shows you how huge of an issue this is.

Dr. Lakshmi Khatri:

Exactly, 1 in 8. So most people, I think, listening in, know somebody or have somebody very close to them who's been diagnosed with breast cancer. So when we compare that sort of 12 to 13% average risk to some of these genes, so that — we'll talk about the BRCA gene, because that was the one we talked about the most — those women have up to a 70% lifetime risk of getting breast cancer, and that is a high number. That's what we call a highly penetrant gene.

And “penetrance” means if you carry that mutation or that variant, how likely are you going to be to get that particular cancer? And there are some genes, the risk that they confer is about 20% or 25%. So there's a big variety of different genetic changes that can contribute to our risk for breast cancer.

John Horton:

Yeah. It sounds like it's all over the board, but the important thing is that it gives you some knowledge and some information so that you can make decisions moving ahead.

Dr. Lakshmi Khatri:

And I think one thing that's really important to think about for people who are listening is that only about 5 to 10% of breast cancer is directly related to one of these pathogenic variants or mutations in these genes. A lot of breast cancer is related to family risk, but many of these families don't carry these genes. But more than half of women who get breast cancer, they don't have an identifiable risk factor, so it's really important that we're all getting screened.

John Horton:

Well, and I think that was such an important point that you brought up, and I'm glad you did. I know I had that in my notes to make sure that we got to it. Because you want to make sure people understand that this genetic mutation isn't the only thing. I mean, there's so many factors that go into whether or not you may get diagnosed with breast cancer, and it's kind of one piece of a very large puzzle.

Dr. Lakshmi Khatri:

Yeah, that's exactly right. It is one piece, but it's an important piece. So I think knowing your family history is really important. And actually, very early on, talking to your primary care doctor or your Ob/Gyn about your family history is important. It's actually recommended nationally that women have a risk assessment done at age 25. And the reason it's so young is because if there is a concerning family history, it's important to identify that risk early on. Because some women, for example, with a BRCA gene mutation, start their breast cancer screening at the age of 25 because we see breast cancer occur earlier in many of these scenarios.

John Horton:

Well, and that kind of leads into what I want to talk about next, which is once you get this information, once you learn you have one of these mutations and that your risk is much higher, like you said, 70% with the BRCA gene, what do you do with that information? What happens next? How does that change your approach moving forward?

Dr. Lakshmi Khatri:

I think a lot of people are afraid to get this information. They don't know that they'll be able to do anything about it. But actually, it's a really empowering thing to have this information because we can be very proactive. I mean, at the bare minimum, everybody should be thinking about what kind of lifestyle changes that they can make to reduce their risk for getting cancer, breast cancer specifically, but any cancer. And that's eating a healthy diet, maintaining a healthy weight, exercise… We know exercise and maintaining muscle mass can reduce our risk of many cancers, but also things like alcohol and smoking — and in particular with breast cancer, alcohol is a big risk factor for getting breast cancer.

But then, for these women who are identified with a genetic variant or gene mutation, there are varying recommendations for something called “enhanced screening.” So the average woman would start their breast cancer screening with a mammogram at age 40, but for these women, they may start earlier. In particular, BRCA, we said was 25 years old. Some people start a little earlier than that. Some people start at the age of 30.

And these women often undergo MRI surveillance along with their mammogram. It's a slightly different way to look at the breast tissue, and it's an ultra-sensitive way to find changes in the breast that could indicate a cancer. So by doing that, you can find something really early because breast cancer is very curable, and this enhanced screening technique is actually really effective in these high-risk women to help find cancer early when we can actually take care of it.

We also have medications at our disposal. So some of the medications that are not chemotherapy, but they block estrogen or other hormones, we can use them to treat breast cancer, but actually, they can be used to prevent breast cancer, too. And they've been studied pretty extensively and can reduce the risk of getting breast cancer by somewhere between 50 to 60%, which is huge.

John Horton:

That's huge. Yeah, that is enormous. Yeah, big difference.

Dr. Lakshmi Khatri:

And you don't take them forever. I mean, you would take these medications between three and five years, and I know people are not necessarily excited about taking medication, but to know that something could be that effective in reducing your risk, like preventing cancer, is pretty real.

John Horton:

Right. Yeah. Cancer-blocking medication seems like, I mean, something you'd be interested in if you knew you had a high risk.

Dr. Lakshmi Khatri:

John, I love that, “cancer-blocking,” I've never used that before, but that might be a term that I use in the future because that's really great. I mean, it's a really good way to think about it. It's a shield, it protects you, and they are really effective.

And then for women at very high risk, so those women who have a risk that's 50% or greater, or they have a very high family history or just a really, what we call “compelling family history,” more than one first-degree relative, somebody at a very young age, they can actually opt for a prophylactic or preventive mastectomy. And so that's actually electively removing your breast tissue before you develop a breast cancer to reduce your risk of getting breast cancer.

And I think it's important to know this is a choice for all women because we can so effectively screen and have these preventive options that surgery isn't a must. It's never something I'm going to recommend, but it's always something I would support in certain scenarios. It's a very personal choice, and it doesn't eliminate your risk for cancer, but it does reduce it quite a bit by 90 to 95%.

John Horton:

Yeah. Hearing all of this, what you just went over, the steps that you can take once you have this information, it makes you realize how important it is maybe to get this, you know, to know. Go looking ahead that, hey, you are more at risk for this because there are things you can do to really lower your risk of having a positive diagnosis.

Dr. Lakshmi Khatri:

Yeah, definitely. And I think for those who are listening, some of the red flags that would prompt you to talk to your doctor about doing genetic testing would be a family history of breast cancer in somebody who was 50 or younger. Any man in your family, a male relative with breast cancer, which is rare, it does happen, but it could mean that there's a genetic mutation. Ovarian cancer in the family, pancreatic cancer. So any significant cancer risk, don't hesitate to talk to your regular doctor about that.

John Horton:

And all we've been talking about is genetics here, and obviously, genetics extends to your family, especially your close relatives. If you get genetic testing, it sounds like it is very important to share that information with your closest relatives because what you found out about you may affect them also.

Dr. Lakshmi Khatri:

Yeah, definitely. So the way that these genes are inherited is, whether they work or not, is you typically get one copy from your mom and you get one copy from your dad. And if you inherit one of those broken copies, that's when we're in a scenario where you have a sort of broken cellular repair mechanism; these are the women or the people who are at high risk for certain cancers. So it means that you could pass it along to your children. So you've got one good working copy and one broken copy, so you could pass either one to your child. And so each of your children would have about a 50% chance of carrying that gene, as would each of your siblings. And so it's then important to make sure that your relatives are aware of this so that they can go and do testing to determine if they're at risk as well.

John Horton:

Yeah. And it sounds like that is an important step. Once you learn this, you got to tell it to the people ahead of you, I guess, on the family tree and kind of beneath you. Because you are passing, or there's a risk that you're passing, that along to them, and then they can start that process a little bit earlier to possibly get early detection and things like that to really protect their health.

Dr. Lakshmi Khatri:

Exactly, exactly.

John Horton:

Is this sort of testing available for everyone? I mean, can someone just walk into the doctor's office and say, "Hey, I'd like to know this. I want to get this genetic testing. When can I start?"

Dr. Lakshmi Khatri:

Yeah, you know what, it's definitely something that is much more readily available and a lot more financially reasonable. It used to cost thousands of dollars to do this, but the technology is such that some companies are offering it for $250. Most of the time when we do genetic testing, we're doing it for people who meet specific criteria to do the testing, and most of the cost is covered.

Now, the question of should everybody be screened for genetic mutations or variants is one that some people are in favor of and some people are not. Remember, we talked about how many variations can exist in a gene. They're not all problematic. And about 25% of the time when we do these panels of genetic testing … so typically, what we'll send people for is a “hereditary cancer panel,” and it's about somewhere between 60 to 80 different genes, so it's not just breast cancer genes.

So when we do those, about 25% of the time, people will have a result that shows a variant of uncertain significance or just a change in the spelling of one of the genes that's never been shown to cause any type of cancer. But that can be troubling for people to get that information. Typically, those variants, eventually, we learn more about them as more people have genetic testing done, and a majority of the time, they're reclassified as completely benign, but not always.

And there are other implications of genetic testing. Interestingly, there are laws, thank goodness, that protect us from being discriminated against in the workplace or with health insurance, trying to get health insurance if you do carry a genetic variant. But there are no laws that protect us from being discriminated against if we're trying to get long-term care insurance or life insurance, and that's really tricky.

And we counsel all of our patients on that before they do their testing, because many of our patients are young. And I mean, I know I didn't have life insurance at 25 years old, so it can be kind of tricky to navigate that.

John Horton:

Yeah, I was going to say, is there an age where if you know you have this higher risk or it runs in your family, where you need to start testing, or you should … is there such a thing as testing too early?

Dr. Lakshmi Khatri:

Yeah. Testing in children is really tricky, philosophically, to have information that you may or may not share with them, especially if it's not going to change anything that you do. Most of these genes don't affect children, at least the ones that I'm kind of managing; they usually cause adult cancer.

So for the breast cancer genes, most of them, not all, but most of them, we'd want to know by age 25. And so that's sort of the kind of age cutoff that we use, which is why I think national recommendations are that women should have a breast cancer risk assessment by 25 years old.

It is heavy information, as you can imagine, even though I've talked to you about all these amazing things that we're able to do to help prevent cancer, and also find that really early, early detection is the key, it can produce a lot of anxiety. And even though we have these numbers that say if there's 100 people with this gene, 30 of them will get cancer, but 70 won't, is often how I might explain a 30% risk for people. But still, in your mind, you feel like you're waiting for something to happen.

And so thankfully, here in our clinic, in our high-risk clinic, we actually have a wonderful team of breast psychologists who help women who are navigating this.

John Horton:

Yeah. It does sound like a very heavy emotional weight to carry. If you learn that you have this, it's got to be tough. And that's wonderful to hear that you have a system in place to help people process what that means and what they can do moving ahead.

Dr. Lakshmi Khatri:

Yeah, it's definitely, it's a lot of information to process. And really, the screening, although it's super effective, the reality is that now this is something you're doing every six months for a long time.

John Horton:

Yeah. It seems like the sort of thing that you want to know, but then once you know, it's tough to have that.

Dr. Lakshmi Khatri:

Right. Yeah.

John Horton:

So if somebody is interested in pursuing genetic testing for breast cancer, what's the first step they should take? And what advice would you give them as they move ahead in that process?

Dr. Lakshmi Khatri:

Yeah, I think making sure that you chat with your family members about their diagnoses and how old they were when they had their cancer. And then, talking about it with either your primary care doctor or your Ob/Gyn, who, if you're already at the Cleveland Clinic, if you're clearly appearing to be high risk for breast cancer, they'll typically send you to our team in the high-risk clinic. But they can also refer you straight to medical genetics, and a geneticist can go through your family history and determine what testing is right for you.

John Horton:

Well, I have to tell you, going to see you and your team, it sounds like it would be a great first step because you have so much information. And I love the way you explained everything, and it seems like this is one of those things that it's important to learn, but then there's a lot you need to do once you get that information.

Dr. Lakshmi Khatri:

Yeah, definitely. I really appreciate you highlighting this topic because I think it's important for people to understand what it really means.

John Horton:

Yeah. Well, thank you so much for explaining it so well, and I'm hoping that we get you in here again to really get into this topic a little bit more.

Dr. Lakshmi Khatri:

It'd be my pleasure.

John Horton:

When it comes to genetic testing for breast cancer, the goal isn't to predict the future. It's to better understand your risk and give you more power to act on it. Start the conversation with your doctor if you think this sort of information might be beneficial to you or your family.

If you liked what you heard today, please hit the subscribe button and leave a comment to share your thoughts. Until next time, be well.

Speaker 3:

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