Presence of BRCA1/2 Mutation Improves Ovarian Cancer Survival

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(ChemotherapyAdvisor) – Women with invasive epithelial ovarian cancer (EOC) and a germline BRCA1 or BRCA2 mutation had improved 5-year overall survival compared with those without the mutation, results of a study in the January 25 issue of JAMA has found. BRCA2 carriers had the best prognosis. The 5-year overall survival was 36% for noncarriers, 44% for BRCA1 carriers and 52% for BRCA2 carriers.

These mutations, which represent “the strongest known genetic risk factors for both breast and EOC,” are found in 6% to 15% of women with EOC, according to Kelly L. Bolton, PhD, of the National Cancer Institute, Bethesda, MD, and colleagues for the EMBRACE, kConFab Investigators, and The Cancer Genome Atlas Research Network.

The investigators pooled data from 26 observational studies on survival of 3,879 women with ovarian cancer followed for variable times between 1987 and 2010. These data included 1,213 EOC cases with BRCA1 (n=909) or BRCA2 (n=304) mutations and 2,666 noncarriers; 1,766 deaths occurred during the 5 years following a diagnosis of EOC.

After adjusting for study and year of diagnosis, women with the BRCA1 and BRCA2 mutations had a more favorable survival than noncarriers that remained after adjustments for stage, grade, histology, and age at diagnosis. These findings confirm a recent Cancer Genome Atlas Project analysis, which reported BRCA2 carriers had improved prognosis. Women who were BRCA1 carriers presented with EOC at an earlier age than those who were BRCA2 carriers.

The study results have important implications for clinical management of patients with EOC, the investigators noted, noting that “given the important prognostic information provided by BRCA1 and BRCA2 status and the potential for personalized treatment in carriers, routine testing of women presenting with high-grade serous EOC may now be warranted.”

“Most immediately, our findings can be used by healthcare professionals for patient counseling regarding expected survival,” they wrote. Women with EOC who are BRCA1 and BRCA2 carriers have been found to respond better than noncarriers to platinum-based chemotherapies. In addition, despite the disease generally being diagnosed at a later stage and higher grade, women with these mutations have improved survival. “If patients could be stratified based on their BRCA status, their treatment could be tailored to reflect this, with noncarriers targeted for more aggressive treatments.”

In an accompanying editorial, David M. Hyman, MD, and David R. Spriggs, MD, of Memorial Sloan-Kettering Cancer Center and Weill Cornell Medical College, New York, wrote that “germline BRCA testing needs to be consistently incorporated into both routine management and future phase 3 trials of ovarian cancer,” the latter to avoid possible confounding of preplanned statistical analysis.

Abstract

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