BRCA2 mutation associated with improved survival, chemotherapy response in ovarian cancer

Yang D. JAMA. 2011;306:1557-1565.

Issue: November 10, 2011

Results from an observational study showed that carriers of the BRCA2 mutation had improved overall survival and response to chemotherapy compared with women with the BRCA wild-type mutation.

BRCA1 was not associated with improved survival or response.

Researchers evaluated multidimensional genomics and clinical data on 316 women diagnosed with high-grade serous ovarian cancer collected by the Cancer Genome Atlas research network for the association between BRCA1/2 deficiencies in ovarian cancer, patient OS and PFS rates and chemotherapy response.

Five-year OS was 61% for BRCA2 mutation carriers (HR=95% CI, 43%-87%) compared with 25% for carriers of wild-type BRCA. There was no significant OS difference between carriers of BRCA1 and wild-type BRCA.

Similarly, BRCA2 mutation carriers had superior PFS compared with wild-type BRCA (HR=0.40; 95% CI, 0.22-0.74). Three years after surgical resection, PFS was 44% for women carrying the BRCA2 mutation compared with just 22% for BRCA1 carriers.

The BRCA2 mutation was also associated with a significantly higher primary chemotherapy sensitivity rate: 100% for BRCA2-mutation vs. 82 for BRCA wild-type and 80% for and BRCA1 carriers. Only 80% of women with the BRCA1 mutation were primary sensitive to platinum-based therapy (P=.02) when compared with BRCA2 mutation carriers.

The BRCA2 mutation was also associated with a median platinum free duration of 18.0 months compared with 11.7 for BRCA wild-type and 12.5 months BRCA1 carriers.

In an accompanying editorial, Victor R. Grann, MD, MPH, and Ramon E. Parsons, MD, PhD, of the Columbia University Medical Center, said the results provide "a major advance in the understanding of the use of new treatments for ovarian cancer among patients with BRCA mutations" and should be evaluated in a randomized clinical trial.

"The discrepancy between response and survival among BRCA1 and BRCA2 mutation carriers should encourage attention to the differences in treatment between the 2 groups, particularly among women with ovarian cancer," Grann and Parsons wrote. "Moreover, these findings should raise the issue that the nature of the deficit in DNA repair detected due to BRCA2 mutation is not equivalent to the deficit due to BRCA1 mutation or hypermethylation. Further refinement in the understanding of the differences in the DNA repair deficits due to BRCA1 vs. BRCA2 mutations could lead to therapy that is better targeted."

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