Genetics, Genetic Testing, and Breast Cancer: Part 2

Jamie DePolo: Hello, everyone. Welcome to this edition of the Breastcancer.org podcast. This is part two of a three-part podcast we are doing with Cristina Nixon, and Cristina is a licensed, certified genetic counselor with the Cancer Risk Assessment and Genetics Program at Main Line Health in Pennsylvania. In addition to counseling patients, she also assists with research, including most recently a study looking at multi-gene panels in BRCA1- and BRCA2-positive families. Cristina has also completed the Cities of Hope intensive course in cancer risk assessment.

Today we’re going to talk about genetic testing, how it might happen, who maybe should be tested or who should consider testing, and how it all works. Cristina, welcome back to our podcast. This has been so helpful. The first time we talked a lot about genes and mutations and abnormal genes, and now we’re actually going to focus on the testing. So, as I understand it, the only way to know for sure if somebody has a genetic mutation is to have genetic testing done. So how does a woman know if genetic testing is right for her? Are there certain aspects of family history that you look at? Are there people who might need genetic testing even if they don’t have a strong family history of breast cancer?

Cristina Nixon: So, I’m going to start to talk about just some general guidelines of when women can start to think about doing genetic testing. There are actually a lot of criteria for when we consider genetic testing, but these are just some general rules of thumb to think about when thinking about whether you need genetic testing or considering genetic testing. So, first of all, we consider a person’s personal history of cancer, so before we even look at the family, if a woman herself has had breast cancer, we look at women who are diagnosed under the age of 50. We also look at women who have a history of breast cancer in addition to any other type of cancer, so if they have had two primary breast cancers or breast cancer and a different type of cancer. We look at women who have triple-negative breast cancer. Women who have a personal history of ovarian cancer as well, even if there is no family history, and also women with a history of pancreatic cancer, that would depend additionally on additional family history as well. And then for men as well, of course if they’ve had pancreatic cancer… For any man who’s had male breast cancer. Then looking at family history, so if a woman herself does not have a personal history of cancer, but is looking at her family, it’s important for her to look at both sides of her family history. A lot of times women will talk to me about their mother’s side of the family but really, they want to also consider dad’s side.

You know, even though we’re thinking about breast cancer, sometimes people believe that they can’t inherit genes from their father related to breast cancer, but, in fact, you can. You’re inheriting genes from both of you parents. And then looking at both sides of the family, if there’s a history of breast cancer in three or more women in the family, no matter how old they were when they were diagnosed with these cancers, that’s reason to consider it. Also, if there are two or more women with breast cancer, if one of them was diagnosed under the age of 50, that’s a reason to consider it. And then also if ovarian cancer is in a close relative in the family, and by close relative I mean a mother, a daughter, a sister, an aunt, and even in some families we look at first cousins as well and great-aunts. Okay?

Jamie DePolo: Okay.

Cristina Nixon: Additionally, we look at ancestry in a family, so for women who have Ashkenazi Jewish ancestry, we can consider genetic testing specifically for the BRCA1 and BRCA2 genes. And that can be, even in some cases if there isn’t any family history of breast or ovarian cancer, if there are limitations to the size of the family or there are a lot of men in the family, we might still consider doing BRCA1 and 2 testing in these women, just based on their ancestry.

Jamie DePolo: Okay. So, that would be an example of somebody, as you said, that didn’t have strong family history but might want to consider testing.

Cristina Nixon: Exactly. And that’s just because the chances of having a mutation in BRCA1 or BRCA2 are higher in individuals who do have Ashkenazi Jewish ancestry.

Jamie DePolo: Okay. Are there any other groups like that, that you can think of, that somebody might want to consider testing even if she didn’t have a strong family history?

Cristina Nixon: No. No, I think that would be the only one.

Jamie DePolo: Okay. That’s good to know. Now, I’m curious, too, about DCIS, which is non-invasive. Do you and anybody that you’re counseling, do you think about testing in the same way, say if the woman has a strong family history of DCIS -- so it’s cancer but not invasive cancer?

Cristina Nixon: Yes. We look at DCIS the same way we would look at an invasive breast cancer. So the criteria that I have just talked about earlier would apply to women who have DCIS or invasive breast cancer.

Jamie DePolo: Okay. So, it’s really not any different.

Cristina Nixon: No.

Jamie DePolo: Okay. Okay. That’s good to know it’s all the same. Now, I know a lot of people are curious about this. What exactly is the process for having genetic testing? Does it have to be recommended to you by your doctor? Is it always preferred to meet with a counselor first? Can you have testing and then meet with a counselor? How does that all work?

Cristina Nixon: Well, I think it can be helpful to start the conversation with your doctor, to review your family history with your doctor, and then sometimes doctors will then refer you to a genetic counselor. It also depends on the genetic counselor that you see. I know with our program, we don’t require a referral from a physician. A patient could just call our number and schedule an appointment or talk to a genetic counselor and get information before scheduling the appointment. But there are some programs that may require that referral from a doctor.

Jamie DePolo: Okay. Oh, go ahead. Sorry.

Cristina Nixon: No. That’s okay. You go ahead.

Jamie DePolo: Well, I was just going to say, could somebody have testing done without meeting with a counselor first? I know it’s preferred to meet with a counselor but…

Cristina Nixon: It also depends on where you live. Sometimes it’s difficult to have access to a genetic counselor, although there is a company called Informed DNA, which does offer genetic counseling over the phone if you aren't in a place where there’s a genetic counselor available to meet with in person. I do highly recommend meeting with a genetic counselor first, just because there are many tests, first of all, that you could consider ordering, and there’s just a lot of information that comes along with genetic testing. And I really feel strongly that it’s important for women and men to understand what results can come out of genetic testing and how that information will impact not only that person but also that person’s family members.

And it also can help just to have the conversation, “Is genetic testing even appropriate for me?” You know, there may still just be confusion there as to, “Is this really necessary?” So, that would be the first step. And then the second step, if it is appropriate, is to determine again, is this information that you really want to have at this point in time? Is it a good time for you to learn this information? Is it information that you want?

Jamie DePolo: Okay.

Cristina Nixon: So, I realize that it’s not always possible to speak with a genetic counselor prior to genetic testing. And there are some physicians that will go ahead and order it for individuals, and then in that case it might be helpful to speak with a genetic counselor after you’ve gotten your test results back to help interpret those test results.

Jamie DePolo: Okay. Yeah, I can’t imagine getting a report like that back and then not having a counselor sit down with me and go through it. Because besides the mutations from talking with you and other counselors, I know there’s often a result called ‘a variant of unknown significance,’ which can be very confusing. And can you talk a little bit about those and what they are?

Cristina Nixon: Sure. So, it is possible with any genetic test to get an inconclusive test result, otherwise known as a variant of uncertain significance. And when that happens, it means that the laboratory sees a change in the DNA of a gene, but the laboratory isn’t quite sure: Is this a change that is a mutation that does increase cancer risk, or is it just a normal variation that does not increase cancer risk? So, we’re not able to make any type of medical recommendations based off of this inconclusive result.

Jamie DePolo: Okay. Which can be kind of… I don’t know… Scary, frightening, anxiety-producing? It’s like, “I’ve got this thing but nobody knows what it means,” basically.

Cristina Nixon: Right. It’s very frustrating, because then not only the healthcare provider but the patient knows then that, “Okay, there’s something in this gene but we don’t know what to do with it. We don’t know what it means.” And so, that’s also part of the counseling up front before you have testing, is to also be aware that an inconclusive result is a possibility.

Jamie DePolo: Okay. And I’m curious, too, these results are kept, and -- so say I had a genetic test, and I got a variant of unknown significance. And then 10 years later, somebody starts doing research on that gene and then they kind of figure out more about what that mutation might mean. Do you ever see women coming back to get retested as more information is coming out?

Cristina Nixon: Well, there’s kind of two different answers to that question. So, if a person has one of these variants of uncertain significance, it’s not that they necessarily have to be retested in the future because, as you said, these results are kept in a database with the laboratory and then of course they’re kept in your chart at your genetic counselor’s office or the doctor’s office. And what happens is eventually the laboratory, through research, will figure out if this variant is a mutation or not, and a lot of the laboratories -- I can’t guarantee that all of them, but a lot of the laboratories -- when these variants get reclassified to either a mutation or to a normal variation, they will re-contact the ordering provider to update that person, and then that provider will reach back out to the patient to update the patient on what their result really is now.

Jamie DePolo: Okay. Okay. I see. So there’s really no need to get retested, in that case.

Cristina Nixon: In that case. Right. Now, retesting can be considered, though, if there are improvements to the technology of the testing. For example, BRCA1 and 2 testing has improved greatly over the years, since the late 1990s when it really became clinically available to have BRCA testing, the testing has improved in the quality of the test since then. So we have had women coming back in to be retested for the BRCA1 and 2 genes. And then, additionally, if there are other genes that have been discovered along the way, women come back in to be tested for those additional breast cancer genes as well.

Jamie DePolo: Okay. Okay. Now, we talked about family history at the beginning. A woman’s family history is likely going to change over time, especially, you know, if she’s a younger woman, as she ages, different people in her family might be diagnosed with different cancers. Is there a good way that you would recommend for somebody to sort of keep track of these and make sure that her doctor is aware of all these things?

Cristina Nixon: I think making it part of a discussion during a yearly physical would be helpful, with your physician, or with your annual gynecologic check with the gynecologist, it might be helpful to just again revisit the family history. I know a lot of doctors’ offices will ask about family history when you’re coming in as a new patient to the practice, but not all physicians will necessarily take the time to update your family history. So it may fall more on the patient herself to try to remember to bring up any changes in the family history, to try to think of it as part of just your physical exam. Your family history is just as important as your own medical history.

Jamie DePolo: Okay. Okay. Yeah, that’s a tough one, too, especially if someone is not in touch with all of her family, to keep track of all of those things.

Cristina Nixon: Right. It’s harder if you have a really large family, it can be hard to track down all of those relatives.

Jamie DePolo: Okay. Now when isn’t genetic testing recommended for a woman with breast cancer? Because I know it’s not recommended for every single person who’s diagnosed. Is it simply a family history and, as you said, an ethnicity? Or are there other things that go into that?

Cristina Nixon: So, when a woman would not be recommended to have genetic testing?

Jamie DePolo: Right.

Cristina Nixon: Okay. I would say a woman who is over the age of 50 or postmenopausal, a woman who’s already been through menopause, and does not have a family history of breast cancer or other cancers in the family, and does not have Ashkenazi Jewish ancestry, then that’s an example of where testing may not be appropriate.

Jamie DePolo: Okay. And that’s just because it seems like as you age, it seems like your risk of breast cancer goes up, and it’s probably not a genetic --

Cristina Nixon: Correct. It’s less likely to be hereditary in that case.

Jamie DePolo: Okay. And I know that genetic testing isn’t always recommended for younger women who are diagnosed. And could you talk a little bit about that, like how that decision might be made?

Cristina Nixon: So, even despite your age of when you’re diagnosed or family history, genetic testing… It is a very personal decision. Even though you may meet medical criteria, you know, based on these factors, it also has to be something that a person is psychologically ready to receive the information. So, sometimes… I do ask every patient that comes in, “If you have genetic testing and the results are positive, would you use the information to make decisions about your treatment or to consider preventive things for the future, like increasing your cancer screening or preventive surgery or preventive medication? How would this impact you going forward?” And if a person tells me that it’s really not going to change what they want to do, that they wouldn’t consider these options, they wouldn’t change their treatment, then I don’t see it as being as helpful of a test to that person.

Jamie DePolo: Okay. Does it make a difference if somebody has children or not? Or no?

Cristina Nixon: Well, it can. Sometimes people will have genetic testing just for the family’s information as well, even if they don’t feel they will use it personally, then they look at it as, “This will help my children, my brothers and sisters, nieces and nephews.” Absolutely.

Jamie DePolo: Okay. Now, if someone decides to have genetic testing, how long does it take to get the results?

Cristina Nixon: It depends on the genetic testing that’s being ordered. Some of our tests take as little as a week to come back, like if we are just looking at BRCA1 and 2, there are some labs that will return results within 7 days. But if we’re doing a bigger panel of genes, then the turnaround time might be longer. It might be 2 or 3 weeks. In some cases it might take a month. It just depends on the laboratory doing the testing as well as how much is actually being tested.

Jamie DePolo: Okay. Now, do you ever recommend genetic testing for a woman who has gone through treatment and, say, maybe she was diagnosed 5 or 7 years ago, so the testing really wouldn’t influence treatment decisions, per se. I suppose it could influence how long somebody might take hormonal therapy. But is that ever recommended? And if it is, is it hard for a woman to sort of go back and revisit that whole diagnosis?

Cristina Nixon: So, it definitely is recommended, so, for example, sometimes we’ll see women who may be 70 years old and their breast cancer happened when they were 45. Genetic testing would still be recommended for her because, as we talked about, it would impact her directly, possibly, especially if she still has her ovaries or you know, if there’s a higher risk of developing a second breast cancer, then that’s information that she could potentially use to her benefit. And then additionally, her children, her grandchildren, again, it can really help the family as well. Even though it’s not going to influence, as you said, a treatment decision, it can still help to be preventive and proactive going forward.

Jamie DePolo: Okay. And I guess this would be for all women, not necessarily for just somebody like that, when you’re counseling them, do you talk to people about how to talk to their family about this? And is it ever recommended that maybe others in the family be tested?

Cristina Nixon: We do. Well, I do encourage individuals to talk with their families, I try to encourage them to talk with them before their test results come back so that family members are aware that genetic testing is happening, so that it’s not as much of a shock if the results come back positive -- at least there’s some time to kind of digest that genetic testing is going on. And then especially if testing should come back positive, if there’s a mutation that is detected through the testing, we are available to help individuals share this information with family members.

It can be difficult, especially if they have to reach out, maybe, to siblings or children that they haven’t been speaking to.That can be especially hard. So sometimes we’ll help individuals draft written letters that can be sent to family members, not necessarily with a specific test result, but just general information to tell them that they had genetic testing and that there was something found through the testing and that if they want more information, that they can reach back out to them. And then there are other scenarios, too, where it can be difficult, especially if there is a known mutation in a family and a family member may test negative for that mutation, there can be something called survivor guilt, where a person may feel very badly that their family has this gene mutation and they’ve been going through cancer and watching their family members go through treatment, and they themselves have not inherited this risk. There can be a lot of guilt associated with that.

Jamie DePolo: Okay, I’m sure. And I’m sure you also run into the situation, too, where one person wants to be tested and then… I’ll just pull out an example… Perhaps she has children and two of the three children are for it and one is not and doesn’t want to know, and then that becomes a very difficult situation within the family.

Cristina Nixon: Yes. Yes. As we all know, there are many different personalities within families, and just with genetic testing as well, you know, you’re going to have some family members that are very pro-testing and kind of take charge and take the lead on it, and then you’re going to have other family members that really don’t want the information. And I think it’s important for people to realize that they have to respect each individual’s decision as to whether they test or not and whether they want to learn this information or not.

Jamie DePolo: Okay. And one last question before I let you go, is genetic testing usually covered by insurance? Does it depend on the situation? Do you have a sense of how many people pay out of pocket or how many people get coverage?

Cristina Nixon: Sure. So, most insurances do cover genetic testing, but a lot of insurances also have their own criteria that’s based on family history and personal history of cancer. So some of the general guidelines that I mentioned at the beginning, those are a lot of the guidelines that insurance companies will use. It’s not to say that they will follow all of those rules of thumb, but again, that’s where a genetic counselor can help. If you have a family history and you’re not sure, are you meeting your insurance’s criteria? Does your insurance even have criteria? There are some insurances that do not. We can help sort that out.