Recommendations for Molecular Testing in Advanced OC



Bradley J. Monk, MD, FACS, FACOG: So, Michael, you’ve been one of our leaders in translational science; what’s the molecular testing now that we do once we’ve operated on a patient or begun chemotherapy? Is it just a germline test? And if so, which one? Or do we also do germline and then test the tissue, which is called somatic testing?

Michael J. Birrer, MD, PhD: Brad, that’s a great question and, again, another area that has undergone huge evolution in the last 5 to 10 years. So, we’ve always known that 8% of ovarian cancer patients have a strong family history and these are likely to be BRCA1 or BRCA2 carriers, and that’s been around for a while. But what’s changed is that we now know there’s probably another at least 8%, maybe as high as 15% of patients, who have a germline mutation without a family history in BRCA1 and BRCA2. And in addition, may have a germline mutation in some of the other genes in the family going way back.

So, this has huge implications because these ladies come in, they have a diagnosis of ovarian cancer and they don’t realize that they have a germline mutation in one of these genes.

Bradley J. Monk, MD, FACS, FACOG: In the family.

Michael J. Birrer, MD, PhD: In the family. And so, I think that’s been the huge step forward and it’s a huge service to our patients to recognize that, and insist that they get testing. Now that’s been universally agreed upon by all the professional organizations.

Bradley J. Monk, MD, FACS, FACOG: NCCN [National Comprehensive Cancer Network], ASCO [American Society of Clinical Oncology], Society of Gynecologic Oncology—they test everyone for germline, and they say test for BRCA, but you tell me [to do a panel test] and I agree.

Michael J. Birrer, MD, PhD: And I would say that despite the data we don’t do a great job in this country yet in testing everybody. The numbers I saw are between 20% and 30% of ovarian cancer patients are being tested. So, we need to do a better job at working at that and these kinds of discussions will hopefully help. Panel testing is what I do. I think it’s here to stay. And then the only debate is what you alluded to—I think some individuals in the community are going to first test the tumor rather than germline. And then if the tumor is positive, go back to the patient to test for germline.

Bradley J. Monk, MD, FACS, FACOG: So, if the tumor is negative, the germline’s always negative?

Michael J. Birrer, MD, PhD: Correct, that’s right.

Ursula A. Matulonis, MD: Do you think that’s 100%?

Michael J. Birrer, MD, PhD: Well, this is the issue isn’t it? I actually think that is the case. I think that’s the case biologically; it’s a technical issue.

Ursula A. Matulonis, MD: Correct, yes.

Michael J. Birrer, MD, PhD: So, if you get a piece of tumor that has a lot of nontumor stuff in it, you may miss it. So that’s a concern. I don’t know; the numbers I’ve seen on the frequency of that is pretty low.

Ursula A. Matulonis, MD: Two percent or so.

Michael J. Birrer, MD, PhD: Yes. But I think what’s happening is, it’s a practical issue. So, you’re in the community, you’re busy, you’re working hard, if you refer a patient upfront to a genetic counselor and to get germline testing, it might take several months. So, the reflex is okay, I’ll send this off and I’ll go from there. But yes, it does have some challenges.

Bradley J. Monk, MD, FACS, FACOG: You know you say that, interestingly, because we’re going to talk about decisions that need to be made early in the treatment of that patient. And quite frankly, I don’t have time to get authorization for genetic counseling and send it off to some [laboratory] and wait for 2 months.

So, counseling is important, but we have enabled and empowered our nurse practitioners to counsel, and so we have a whole process and an SOP [standard operating procedure] in place. You know all you have to do is swab the cheek. So, we think the testing for the tumor, although biologically important, is too much work. I can have a newly diagnosed patient and I can activate that clinical pathway, and that patient will be tested. Then as she starts her first cycle of chemotherapy, I can begin to know whether, quite frankly, we’ll get to it, whether I should start bevacizumab [Avastin], or withhold and treat her with a PARP [poly ADB ribose polymerase] inhibitor and maintenance. The PARP inhibitor maintenance opportunity is only for the BRCA patients. But you may start a patient on bevacizumab without having the BRCA information, and then when you know, you’re going to stop it, and then it becomes all confusing. So, tell us what you’re doing in Boston.

Ursula A. Matulonis, MD: I think these are all really important points, and especially what we’re going to talk about in SOLO-1 [trial], where it’s really imperative not just to have this information for the patient’s family, but for her treatment.

Bradley J. Monk, MD, FACS, FACOG: Right now.

Ursula A. Matulonis, MD: I think for us right now in Boston what we’re doing is germline testing. We’re doing panel testing, really based upon the fact that it’s the high-risk mutations—not just BRCA1 and [BRCA2]. But there are at least 9 others that are reported through Mike’s paper that collaborated with the University of Washington showing other genes involved in the high-risk genetics of ovarian cancer.

So, the patient’s diagnosed; first discussion is around treatment, and then the second point is about [the] need to get germline testing now. We try to get the germline testing done. We’d start it within the first 3 weeks after I see that patient initially.

Bradley J. Monk, MD, FACS, FACOG: Timing is important. So we’re getting somewhere in testing.

Michael J. Birrer, MD, PhD: Brad, can I just interrupt you, and emphasize again, based on that paper, it’s independent of histology and age.

: Family history.

Michael J. Birrer, MD, PhD: Everybody should get tested.

Ursula A. Matulonis, MD: Everybody, regardless.

Bradley J. Monk, MD, FACS, FACOG: NCCN and ASCO recommend it. So, we’re getting somewhere. Every patient needs an operation in the beginning or between the third and the fourth cycle. Every patient needs BRCA testing early, probably a panel, and maybe even the tumor, and then chemotherapy.

Transcript Edited for Clarity

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