Hi, welcome back to An Introduction to Breast Cancer. I'm so glad you chose to join me today for my guest interview with Dr. Erin Hoftstatter. Erin is a breast medical oncologist and the co-director of cancer genetics, here at Yale Cancer Center. We're going to talk about genetics with her. Thank you so much for joining me. >> Thank you for having me. >> So, Erin, we've been talking a lot about breast cancer genetics, and I think a lot has come to light with celebrities coming out notifying the public that they've had genetic mutations. How has that affected people's perception about genetics in your practice? >> Well, it's been a welcome addition to the conversation. In fact, I think it's initiated the conversation for a lot of patients and really, the public. Before, I think there's for many, many years, been a stigma associated with these genetic mutations. Many people don't want to talk about it, they're afraid of talking about it. That's really evolved over the past 10 to 15 years but folks like Angelina Jolie making it part of dinner table conversation for example, I think, has been the really beneficial in terms of making it part of the conversation really embracing the opportunity to prevent breast cancer and ovarian cancer when we can. From a practical standpoint it has increased referrals to genetic counseling programs quite substantially across the country. Again, which I perceive as a beneficial thing, it may translate to longer wait times for patients, but I'd say that most programs have caught up by now. But overall I think it's been very very positive. >> But I would think that there's still some stigma or at least some fear about what those results mean. I mean, can it impact their ability to get life insurance? Or does it impact their employ-ability? Have patients come to you with those concerns? >> Yes. >> And what do you tell them? >> Yeah, that's a very common question. And one that is commonly addressed and really is meant to be addressed with genetic counseling. And that's one of the reasons why we recommend that many people, if not all people, undergoing genetic counseling and testing get the counseling before the test is sent. There is federal legislation in place in terms of the GINA Act, which does protect against health insurance discrimination. It protects against employment discrimination so that people don't have to fear that they might lose their job or that they might not be able to get health insurance because of testing positive or even testing at all for these genetic mutations such as BRCA1 and 2. It does not protect against life insurance. And so commonly we do recommend that patients who are considering undergoing genetic testing perhaps get life insurance if that's important to them before they test. There hasn't been widespread discrimination for life insurance, or denial of life insurance that's been documented to date, yet there's no federal legislation to protect against that. So in general, a recommendation is to obtain life insurance before the testing gets sent. >> So it's interesting that you bring up legislation. One of the big pieces of legislation that came out just a few years ago, was the Supreme Court who overturned Myriad's kind of hold on the patent for BRCA one and two. What impact has that had in terms of genetic testing? >> The impact of that Supreme Court decision to overturn the patent that Myriad had held to date on BRCA one and two testing has been really revolutionary. Within hours of that patent being overturned, several other companies who perform genetic testing entered the field. Literally within hours, emails were being sent to many of us providers saying, we have this test for lower cost, we have this test for a lower cost. So I think it has made obtaining genetic testing more widespread. It has introduced competition into the market, so as a result prices have come down. It also was, I would say, a landmark in the developing of panel testing. Because now that BRCA1 and 2 could be included in a panel of genes, and this gene test sent from other companies, it provide a lot more options for providers and for patients to choose which test and at what time. >> So, that brings up panel testing so, should most patients undergo panel testing now that this is available or do you still pick and choose? >> We still pick and choose and right now, based on the information that we have about various genes on the panels. I think it's still appropriate to pick and choose as opposed to blindly sending a panel. We are still learning so much about different genes. Everybody talks in terms of breast cancer about the BRCA1 and BRCA2 genes. Those have been well studied for 15 to 20 years, and we're still learning about what we should do with these mutations. There are many other genes included on these panels and some of these panels might test for five or six genes, some panels test for over 40 genes. Many of the times if you send a panel the results may not match the pattern of cancer in a family. So what do you do for example with a patient who might be found to have a CDH1 mutation, which is strongly predictive of hereditary gastric cancer. There's also an association with lobular breast cancer. But if you send that in a patient, who has no family history of gastric cancer, how are we to council that patient? Should they get a prophylactic gastrectomy, for example. Those are the kinds of decisions that, in the right family history, you might recommend that. But if you're finding these things blindly, we just don't have the experience or the factual data yet to have firm Consultations and firm recommendation for these patients. Some people are comfortable with those unknowns and other patients might suddenly be very fearful of, what the heck do I do with this mutation when you can't give me strict guidelines on what I'm supposed to do? So that's why at this point we're still very careful about who we send. If there's any suggestion of multiple cancer syndromes in the family for example when you see breast and ovarian and colon cancer clustered in the family you could see a link with breast and ovarian cancer with BRCA1 and two, or perhaps that breast cancer's a red herring, and the family really more speaks to something like Lynch syndrome, with the colon and the ovarian cancer. A panel in that situation might be appropriate, because it's just more cost effective to send a panel looking at multiple syndromes at once. Young breast cancer patients, those diagnosed at the age of 35 or younger, you might think again about BRCA1 and 2. It's very common, but there's a rare syndrome, Li–Fraumeni syndrome, with a P53 notation, it is exceedingly rare, but is something that we might think about in a patient. Sometimes these panels are set up so that you can reflex and so you might start with BRCA 1 and 2 and if that's negative then go on to test other highly penetrant or moderate penetrant genes. I think the other difficult thing about the panel is that different genes have different levels of penetrants, as I just mentioned there are very, very strong genes that are strongly predictive of developing a cancer. There are others that are more moderate penetrants, such as CHEK2, PALB2, where it raises the risk of breast cancer somewhat, but certainly not to the level of BRCA 1 and 2. So then the question is what do you do when you get, let's say, a PALB2 variant, or a PALB2 mutation back? Are you recommending mastectomy? Are you recommending breast MRI? Again, those guidelines are not entirely clear, and sometimes that can be stressful for a patient and a provider, quite frankly, to try to come up with what do we do, what is actionable with this panel? And some providers choose not to send the panel unless there's something medically actionable that they're going to find. >> So, how are patients really using all of this new information? Do you find that they're finding it empowering or do you find that they're really kind of getting more scared about their genetic risks? >> I think they're, I think it's a spectrum of patients. I think some patients are very comfortable with the idea of, let's just send for everything. I'm not afraid of what we find. And I think there are others who may be so fearful of the implications for themselves or for their family members that it does take extensive counseling to convince them that perhaps sending BRC one and two alone is a good idea. I think the other issue with a panel testing is not just the possibility of finding deleterious mutations in genes we weren't expecting, but the very very common phenomenon of finding a variant of uncertain significance. There is recent data that just suggested that on these very large panels the variant rate can be as high as 40%. So it's almost a 50/50 chance you send it off, you're going to get back a variant, which means it's not quite a mutation, but it's not normal. Does it convey cancer risk, does it not, what do you do with that as a provider, what are the medical guidelines, it's very, very unclear. And so, you know, I think there's two schools of thought one is, don't send it until we know what we're doing with it but, the other school of thought is what we don't know, we won't know unless we look so, this feel is revolving rapidly. There are movements across the country, both provider, I should say institution and patient driven, to try and collect large databases of patients who are getting these panels done. It's called the PROMPT study where patients sign on to PROMPT, they are able to input their particular mutation, their particular variant, and their particular family history and the hope is, by compiling this data, it's very much a grass roots effort. By compiling this data that with time we will be able to sort out what we should be doing with these panels. >> Fantastic. So, last question, where is the future of breast cancer genetics? >> That is a very great question. My hope is that where breast cancer genetics really takes off is in the field of prevention. In my mind, to find a mutation once a diagnosis of breast cancer has been made, in a way, it's almost too late. It's beneficial for the rest of the family, but it would be wonderful if we could really find these mutations in families where you know, you are expecting to see a mutation and then you can act on it for the patient, and for their family members. Are we at a point where every single breast cancer should get a panel done? I'm not sure we're there yet, and i'm not sure if and when that would ever be appropriate. But I do hope that with broader insurance coverage, with clear guidelines, and what the implications of gene testing and panel testing might be, that we will find more of these mutations. We'll be able to prevent more cancers and that it will become commonplace and will no longer hold a stigma. >> Excellent, well thank you so much for joining me. >> Thank you very much.
