Does BRCA2+ Confer a Survival Advantage in Ovarian Cancer?

Maurie Markman, MD


September 13, 2012

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Hello. I am Dr. Maurie Markman from Cancer Treatment Centers of America in Philadelphia, Pennsylvania. I want to briefly discuss a very interesting paper that appeared in the August 1, 2012, issue of Cancer: "Improved Survival for BRCA2 Associated Serous Ovarian Cancer Compared with Both BRCA-Negative and BRCA1-Associated Serous Ovarian Cancer."[1]

We have recognized for quite a while that patients who have the genetic abnormality in BRCA1 have an overall improved survival with ovarian cancer. [This improved survival] presumably is related to the fact that DNA repair, which is defective in this patient population in terms of their normal tissue and is hypothesized to be the reason for their higher incidence of ovarian cancer, is also associated with an inability to repair DNA damage from platinum [chemotherapy] agents, resulting in improved outcome. However, BRCA1 and BRCA2 have been lumped together from the perspective of the favorable prognosis in this setting.

This retrospective analysis involved 190 patients who had a genetic analysis performed, and it included 30 patients with BRCA1-positive disease, 17 patients with BRCA2-positive disease, and the remainder, who were BRCA negative. This analysis demonstrated that the patients with BRCA2 abnormalities had a strikingly favorable survival, with a hazard ratio of 0.2 and a P value of .007. Patients with BRCA1 did not appear to have improved survival associated with that genetic defect, compared with the wild-type population.

Certainly this was a limited number of total patients and the outcome must not be considered definitive, but I believe that it does suggest that we need to look again at the question of whether BRCA1 and BRCA2 are the same in terms of the impact on outcome in ovarian cancer. This study needs to be followed up with data from other investigators to see if it can be confirmed in a larger patient population.

I encourage you to look at this very interesting paper from the August 1 issue of Cancer, which demonstrates the significance of these genetic abnormalities and the fact that we obviously have much more to learn as we move along in this very interesting era of molecular analysis of tumors, to see how such information can affect outcome.

I thank you for your attention.