Expert Views on Therapy for Ovarian, Fallopian, and Peritoneal Cancers - Episode 3
Transcript:Bradley J. Monk, MD: I think we understand what we can test, germline or tumor. We understand why to test, whether it be germline or tumor. When do we test, Katie?
Kathleen N. Moore, MD: Well, as you alluded to, we’re catching folks up right now. So, all of these patients that have been in survivorship or all of these multiply treated recurrent patients, as they come into our clinics, we’re testing them now. But really, I think that we’re moving toward that diagnosis. Once you know that someone has a confirmed diagnosis of an epithelial ovarian cancer, we’re offering the opportunity to undergo genetic testing, and hopefully genetic counseling as well, so you know at the beginning.
As we said, from a prognostic standpoint, we have frontline clinical trials that would be informed potentially by knowing whether or not they have a germline BRCA mutation or not. And also, you feel bad for these patients who have been out there for 8 years or 10 years and you’re finally testing them and their families are sitting around, at risk, for years. And I certainly have seen a family member come down with a preventable ovarian cancer who, if we had tested her, if we had known 5 years ago or 10 years ago, we could have prevented that. So, it’s really critically important.
Bradley J. Monk, MD: Do you guys use genetic counselors? Everybody needs to be counseled, but in my practice, the nurse practitioner can counsel, I can counsel, and I also have genetic counselors. Who’s the best person to counsel a patient before testing?
Angeles Alvarez Secord, MD: I think it goes beyond who’s the best person. I think the critical issue is how many patients were missing or missed opportunities to get the test. So, even if you refer to a genetic counselor, about 30% of patients don’t undergo testing and that’s where the point of care testing at initial diagnosis is so appealing. And also, going back to the tumor testing, my one concern I didn’t mention earlier about the tumor testing is, do we know for sure that there’s not tumor heterogeneity that can affect a somatic mutation? It’s not necessarily the germline—you’d expect all the cells to have that—but perhaps a somatic mutation. But I still find that idea very appealing, and we would be able to catch a far greater number of patients who have these mutations rather than waiting for the genetic counselor’s appointment and for them to keep that appointment.
Robert L. Coleman, MD: Before we go on, we focused a lot on BRCA1 and BRCA2 testing. We haven’t talked about panel testing, and I wonder how many of you all do that and why are we doing it reflexively?
Bradley J. Monk, MD: What do you mean reflexively?
Robert L. Coleman, MD: Meaning we said that we test all nonmucinous or, as you said, all epithelial ovarian cancers. Why are we doing that instead of family history and all of the risk algorithms that we’ve done before?
Bradley J. Monk, MD: Because family history and age of onset don’t predict the chance of being positive. It’s not global.
Thomas Herzog, MD: They’re predictive.
Robert L. Coleman, MD: Well, the problem is they don’t predict.
Kathleen N. Moore, MD: But they miss.
Thomas Herzog, MD: They miss such a high percentage.
Kathleen N. Moore, MD: Right. We have the data from Washington, Pennington’s paper, that I think was eye-opening to a lot of people. If you rely on family history alone, you miss 30%. If you base it on age, this is all young ovarian cancer. But you have patients in their 70s who are diagnosed, and there’s histology even, which some people really, really believe that it’s only a high-grade serous issue. We’ve seen these mutations rarely in mucinous, but it’s not 0.
Thomas Herzog, MD: But it’s not 0 even in low-grade.
Robert L. Coleman, MD: In low-grade, and in endometrioids, absolutely.
Bradley J. Monk, MD: So, it may not be related to the cancer pathway. I use panels.
Robert L. Coleman, MD: We do, too.
Angeles Alvarez Secord, MD: We do.
Bradley J. Monk, MD: So, that’s an interesting point. Test early, use panels, and get good counseling. But beware that if you refer to the genetic counselor, it still may not get done. Test the tumor, test the patient for germline.
Kathleen N. Moore, MD: Panels are critically important. As we now know, there are 3 other high-penetrance genes and maybe 4, if PALB2 actually comes in there. They’re low-frequency, but you’re not going to find them if you don’t do panel testing.
Robert L. Coleman, MD: Right, if you don’t do them.
Kathleen N. Moore, MD: And those are patients whose families we counsel in the same way that we counsel our BRCA patients. So, you want to catch those 1% to 2%.
Angeles Alvarez Secord, MD: You can do customized panels now, so you don’t have to do the full panel if you want to avoid detecting a gene of uncertain significance. And what are you going to do with that gene? The term that they use is “actionable,” and while it may not be the best term, it does apply to the situation where patients get told they had a variant or they have a gene of uncertain significance. But we don’t know what to do with that. That causes a lot of distress.
Bradley J. Monk, MD: Well, I think that’s very helpful. Thank you for discussing genetic testing and the molecular biology involved in ovarian cancer.
Transcript Edited for Clarity