Breast Cancer Risks: Guidelines for Genetic Testing

Transcript:Adam M. Brufsky, MD, PhD: The National Comprehensive Cancer Network (NCCN) Guidelines for hereditary breast cancer testing are evolving. The latest ones came out a couple of months ago in early 2016. These guidelines are actually very good. They’re very precise as to what the criteria are for genetic testing. And, in fact, the way the guidelines work is that they have a series of guidelines that are suggestive of a familial risk, and they would like the first step to be some sort of genetic evaluation before sequencing. And I think that’s very, very important. I think that having professionals that are involved who are very experienced in hereditary breast cancer testing and screening is very important. The reason for that is that a lot of the genes, especially in these multigene panels, may have variants that we don’t know actually cause a risk mutation or not, what we call a deleterious mutation or a pathogenic mutation. A lot of these genes have mutations in them that may be part of the normal human variation. We just don’t have enough data to determine what those mutations may do.

And so what the guidelines do, which I think is really nice and really important, is recognize the uncertainty associated with some of the genes that are found to be mutated, especially when someone does undergo a multi-gene panel. They do recommend counseling by someone who’s experienced in this testing and in genetic counseling to help interpret the testing.

Harold J. Burstein, MD, PhD: Many groups are trying to articulate guidelines for which patients get tested and what kinds of tests should be ordered for situations of hereditary breast and ovarian cancer. Historically, it’s been BRCA1 and BRCA2 testing, and now as these larger panels are becoming available, other groups are weighing in on making sure that testing information is available. I think there are a couple of things to watch as these guidelines evolve. The first is that, in general, the guidelines support broad accessibility of testing to patients. And so there shouldn’t be a situation where you have to piecemeal ask for one gene, and then another gene, and then another gene unless the clinical situation really suggests that’s the best approach. Overall, you’re going to move to more multi-panel testing. The cost of these things are coming down, the information is going up, And the chance that you want to get a test—and then wait 6 weeks, and get a negative result, and then do another test—is going down. So, most of the time we’re talking about panel testing as the future for a lot of women where there isn’t a known specific syndrome.

And what a lot of the groups, NCCN and ASCO, have been advocating for is two things. One is to make sure that insurance coverage exists for patients who need the panel testing, so that patients who have what looks like hereditary but not BRCA1 and BRCA2 testing can get full panel testing. And the second is to try and educate clinicians, and genetics counselors, and primary care providers about which women really need testing and which do not. At the moment, it’s still premature to just recommend blanket testing of huge populations of people who aren’t at greater than average risk. That just generates a lot of genetic noise and information that isn’t helpful. So, they really want to help people understand where the tests fit and who should get testing.

Claudine Isaacs, MD: When we think about the best practices for how we should be thinking about genetic testing for somebody who we suspect might have a hereditary predisposition to breast cancer, I really feel—even more so today—that it’s really important to get genetic professionals in this. The whole concept of genetic counseling as part of the process is critically important. It’s important because genetic testing is a little different than most of the tests that we do in medicine. That test not only has profound implications for the individual that you’re sitting across from but also for their whole family. It’s not just that their family hopefully cares about what happens to that person, it’s that it has direct medical implications for the other family members. And part of the genetic counseling process is to really describe that and to go through that. And, as we’ve already alluded to, the whole idea of what we choose to test for these days is increasing and complicated. This landscape has changed tremendously.

So, we now can think about single gene testing. We can think about multi-gene panel testing, which panel is the most appropriate panel? And the genetic counselors or genetic specialists are the ones who have the greatest expertise in this, and they also have the greatest expertise with the different panels and understand which one may make more sense for a particular patient. It’s not only helping in terms of all the issues that go around genetic counseling and testing, it’s how you communicate those results to other family members, it’s how to actually interpret a true positive result. Or how about a negative result? Well, that depends on the context of the family history. It depends on how much testing is done, if there’s a variant found, and the critical importance of continued relationship with that individual because those variants should be reclassified. And that means the provider who delivered the testing needs to contact the patient down the line, and that may be 2, 3, 4, 5 years down the line if that variant gets reclassified.

In my mind, the best way to provide genetic testing is within the context of genetic counseling prior to the testing so somebody understands it. That genetic counseling session involves a discussion of the potential implications, choices for the patient about what testing he/she would want to pursue, and then how to share that information with family members, and then also the interpretation of the test result at the time that the test result comes back.

Transcript Edited for Clarity