Breast Cancer and Genetic Counseling

Transcript:Claudine Isaacs, MD: When we’re thinking about offering genetic testing to an individual, I think it’s very important that they have genetic counseling as part of that process. And the reason for the genetic counseling is we’re supposed to get three-generation pedigrees. That’s often difficult for us to do in clinic, but it’s really important to get a broad family history. Patients often don’t know that much about their cousins, and their aunts, and their uncles.

Typically, before a genetic counseling session, they are sent materials so that they can try and gather that information from family members, and genetic counselors will also try and get a verified family history. Often, my favorite is when people say, “Oh, my great aunt had stomach cancer, and I wonder, is that really stomach cancer or is that ovarian cancer, and do we really know?” That’s part of the genetic counseling process, to really get a good family history, because that will form the basis of determining which test is most reasonable. First of all, should the individual be tested or not? Some lower-risk patients show up for genetic testing, and it’s really not indicated or appropriate for them to get testing. So, to help determine whether they should get tested and if they should get tested, to then think about what the most appropriate testing options are. And the genetic counselor will spend a fair amount of time with a patient discussing the different options—single gene testing or limited testing versus broader testing—and possible implications of those different tests. And then also discussing how information could impact other family members and the implications of a positive test result for the individual. If they test positive, what does that mean in terms of their cancer risk? What does that mean or what could that mean in terms of their screening or prevention options? So, the patient can be fully informed prior to deciding whether to proceed with testing or not.

And then once they actually undergo testing, there is usually a posttest counseling session that can either happen in person or by phone, where the counselor would describe the test results and discuss the implications in terms of management, and in terms of other family members, what the impact could be. One of the important things that we need to think of, as well, is what are the possible outcomes when we actually send a test, a genetic test, in? I’d like to think of it as clear answers. What can we really understand? So, a clear answer is that there is a deleterious mutation. That means that somebody has, for instance, a BRCA1 or a BRCA2 mutation, or a mutation in PTEN, or a mutation in another gene. And we know that that carries with it certain risks, and we have clear guidelines for management for those individuals so you could have a deleterious mutation identified.

Another clear result is that you test an unaffected family member in a family where you know there’s a mutation present. Most of these genes are inherited in an autosomal dominant fashion, which means that somebody has a 50% chance of getting it, but they have a 50% chance of not getting it. And so they could have a true negative. There is a mutation in their family; there’s no other significant family history of anything. They get tested for that mutation, and they don’t have it; so, they have a true negative. They now are told that that black cloud they were walking around with, and thinking that they were going to get cancer, “Well, you know what, you didn’t get the gene and you have the population risks for cancer.” Those are two very clearly interpretable results.

And then you have the much grayer ones. What if you test somebody and there’s no mutation found? Well, that result could be more informative or less informative, depending on the family history. If you have a family, and that individual that you’re sitting across from had early onset ovarian cancer, and they have a tremendously significant family history, you test them and you even do a panel and nothing comes up. Does that mean they don’t have anything genetic? No, but it depends on the family history that you’re looking at. So, it could mean that we just have other genes out there that we haven’t identified or appropriately tested for. A negative result always has to be interpreted in the context of the family history and in the context of the extent of testing that’s done.

And then the final thing that could happen is you could find one of these variants of uncertain significance, and those are things where we don’t understand whether they’re deleterious or it’s just a benign polymorphism. Those are results that we need increasing knowledge about, and that’s where some of these registries that are out there, like the Prompt and other registries, will help us reclassify some of these variants of uncertain significance.

As we’ve mentioned, it’s not uncommon when you do multi-gene panel testing that you find variants of uncertain significance or you find a mutation in a gene where we don’t fully understand the cancer risks yet. And so there are a number of registries that are available to our patients, and these include some national registries, some international registries. One of the ones that I find easiest, and we often tell our patients about, is a registry known as Prompt, and the patients actually self-enter their data into it. And it’s a way of accumulating across the country. You don’t have to be part of an institution that has this IRB (institutional review board) approved. Any patient, anywhere, can go online and can enter their information. As we gather more and more information with more and more patients, and more and more family histories about a certain variant or a mutation in a lower-risk gene, I think we’ll be a lot smarter in a few years as we do that. So, I tend to encourage every patient, where we get one of those results, that they go and they enter their information in Prompt so that we can have more data as we go on.

In terms of clinical trials that are out there, there are a lot of questions around what’s the best method of delivery of genetic counseling, for instance. I’ve already alluded to the fact that I think it’s an important component of genetic testing. I live in Washington, DC. I live in an institution that has readily available genetic counselors, but that’s not true everywhere, and that’s complex. If you’re out in the middle of the country or you’re in private practice, you probably don’t have a genetic counselor in your group. One of the things that studies have shown, and our institution published a study not too long ago in JCO (Journal of Clinical Oncology), is that telephone counseling was as effective as in-person counseling. So, there are ways to get genetic counseling done by phone. Many companies actually offer genetic counseling that way, and it’s an important thing for people to be aware of.

Following that, the question that comes up—when we give a genetic result—what does the person actually do with that? Let’s say you know the sister of one of your patients who was unaffected and who’s found to then carry the same mutation as her sister who had breast cancer. What is that unaffected woman doing with those results? Is she availing herself of screening and prevention strategies? There are a number of federally funded studies ongoing that are trying to look at whether there are alternate modes of delivery of that information. The educational material is given in different ways than just that standalone genetic counseling session after somebody gets a test result, where all this information is disseminated; a letter is given. Maybe we should be doing other things to reinforce that.

So, there are a number of studies out there that are addressing those issues, as well, and then addressing some of the behavioral issues that surround genetic testing for multi-gene panel testing. It’s complex. How do patients interpret those results? Do they understand what’s going on when you’re thinking about doing multi-gene panel versus single-panel, single-gene testing? How do they interpret the result that they’re given? There is a lot of active research going on in a number of different areas.

Transcript Edited for Clarity