Robert Coleman, MD
Early identification of BRCA
mutations can significantly help inform future treatment choices for patients with ovarian cancer, with the availability of an ever-growing arsenal of therapies for patients with these alterations, according to interviews with two experts that were conducted at the 2016 ASCO Annual Meeting.
The importance of BRCA
testing for treatment selection continues to be enhanced, with the availability of the PARP inhibitor olaparib (Lynparza), which has shown an improvement in overall survival as a maintenance therapy for patients with ovarian cancer. Moreover, in December 2014, olaparib was approved for the treatment of women with BRCA
-positive advanced ovarian cancer following treatment with three or more prior lines of chemotherapy.
Outside of treatment selection, the identification of germline BRCA
mutations could have broader implications. Identifying this alteration could lead to the prevention of cancer for family members, through screening, testing, and prophylactic measures.
For further insight into the importance of BRCA
interviewed Robert Coleman, MD, and Leslie Randall, MD. Coleman is a professor in the department of Gynecologic Oncology and Reproductive Medicine, University of Texas MD Anderson Cancer Center, and Randall is associate professor, gynecology/ oncology, University of California Irvine.
OncLive: What is the importance of early BRCA testing?
: 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.
Leslie Randall, MD
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, 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 were 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.Randall
: Early BRCA
testing is very important for several reasons, the most of which is identifying patients who have specific tumor biology. Patients with BRCA
mutations tend to be more platinum-sensitive than patients who don't have those mutations. They're also eligible for different clinical trials than patients who don't have those mutations.
In addition to that, identifying these patients will identify them for later on in their treatment line for things like PARP inhibitor therapy, as well as identify those whose family members should maybe be tested for genetic mutations.
What are the current recommendations for BRCA testing?
: 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.