BRCA Mutations Inform Survival In Ovarian Cancer

Robert Coleman, MD

BRCA mutation testing in patients with ovarian cancer could mean a world of difference in treatment, says Robert Coleman, MD.

In an interview withTargeted Oncology, Coleman, professor, department of Gynecologic Oncology and Reproductive Medicine, University of Texas MD Anderson Cancer Center, discusses the survival rates of patients with and without BRCA mutations, as well as the development of the field of genetic study and how it applies to assessing a patient’s risk.

TARGETED ONCOLOGY:Why should oncologists test for BRCA early?Coleman:In the past, it was all about trying to figure out whether or not the patient was a germline carrier, and if they were what that implication would be for their offspring. So with that knowledge, it's much easier to test the family because we know what the mutation is, so the testing is cheaper and more directed. Even if they chose not to get tested, there is still some counseling that can be done in terms of how to lower their individual risk.

In the recent years, with the development of PARP inhibitors I think there is a much better understanding about how DNA repair happens. There is this whole homologous recombination deficiency area that's really exploded. That allows us to use these novel drugs, like olaparib(Lynparza), which has already been approved in the BRCA mutation population. Upcoming very soon are going to be multiple different drugs that'll have multiple indications and this will be really relevant.

The way we did it before was to essentially look at family histories, and with very large families, we can get a very good idea about what the individual risk is. The point was that if we felt that there was at least a 10% chance of finding the mutation for germline sequencing, then we would do it. If it was less than that, we would just offer general counseling.

Now we understand that if the families are not that large, we don't have good detailed history, and we have lots of missing information. We found that actually in the lower risk, predicted risk, we missed the majority of patients that would be BRCA positive. Because of those factors, we now recommend to get it done at diagnosis.

TARGETED ONCOLOGY:Are there guidelines that support BRCA testing?Coleman:The guidelines say that patients should get it at the diagnosis. What we've learned now is that some of the other histology types have enough of a frequency that it's worth testing as well. Outside mucinous tumors, we've seen germline testing across the board. We believe the high-grade serous guidelines should be expanded.

TARGETED ONCOLOGY:What would you say the prevalence of BRCA is in patients with ovarian cancer?

Coleman:

It's hard to answer. Prevalence means that if I were to sample the population today, how many of the 200,000 women that are alive actually have BRCA mutation? From an incidence standpoint, we know if you combine somatic and the germline, you get around 20% to 25%, but those patients are more likely to be alive at a longer duration of time. While the prevalence of ovarian cancer is around 190,000 cases, the proportion of those patients that are BRCA is probably higher than the 20% to 25% that we quote.

I don't know that we know exactly what that proportion is, but the 5-year survivors are much more likely to have the BRCA mutation or at least an HRD state than the earlier survivors.

TARGETED ONCOLOGY:What is the difference in terms of germline versus somatic BRCA alterations?

Coleman:

For BRCA, at least the data that we have, looks very much the same. We don't have as much data on the other non-BRCA germ-line that might be associated with familial or genetic risk, and what their likelihood is, but that field is expanding and we should have some better clarity as time goes on.