BRCA1 and BRCA2 Mutations Yield Better Prognosis in Ovarian Cancer Patients

The strongest known genetic risk factors for developing ovarian cancer led to better overall survival after 5 years, according to a study published on Wednesday in the Journal of the American Medical Association.

Germline mutations in the BRCA1 and BRCA2 tumor suppressor genes are found in 6% to 15% of patients with epithelial ovarian cancer (EOC). In general, patients who express these mutations are more likely to be diagnosed with a higher grade and advanced stage of the disease. However, this latest study suggests that those same patients have a better overall prognosis.

The authors performed a pooled analysis of 26 observational studies on the survival of women with ovarian cancer and compared the survival of 909 EOC patients with a BRCA1 mutation and 304 patients with a BRCA2 mutation to 2666 noncarriers who were observed between 1987 and 2010.

In patients who carried the BRCA1 mutation, the 5-year overall survival (OS) rate was 44% (95% CI, 40%-48%); in patients with BRCA2, 5-year OS was 52% (95% CI, 46%-58%). Compared with noncarriers, these rates were statistically significantly (P < .001 for both). Overall survival in noncarriers was 36% (95% CI, 34%-38%). After adjustment for study site and year of diagnosis, both BRCA1 and BRCA2 carriers demonstrated more favorable survival than noncarriers: for BRCA1, 0.78 hazard ratio (HR), (95% CI, 0.68-0.89, P < .001); for BRCA2, HR 0.61 (95% CI, 0.50-0.76, P < .001).

However, when the results were stratified based on the grade and adjusted for other prognostic factors, a survival advantage was not found for patients with low-grade disease in both BRCA1 (HR 2.66; 95% CI, 0.86-8.17, P = .9) and BRCA2 (HR 3.86; 95% CI, 0.59-25.15, P = .16) versus noncarriers. The researchers note that these results were based on small numbers and that larger studies are needed to confirm them, but they suggest that “disruptions of the BRCA1/2 pathways may not be as important in the etiology of these tumors, supporting evidence of etiologic heterogeneity between high- and low-grade serous carcinomas from other studies.”

For the overall study results, the authors suggest that improved survival for BRCA1 and BRCA2 carriers versus noncarriers could be due to biological differences, their response to therapeutic agents, or a combination of the two. In addition, BRCA1/2 carriers could also have differences in aspects of tumor biology not measured in this study.

The analysis is based on a heterogenous study population, which is both a strength and a weakness, according to the authors, since the pooled trials included women of different ethnic groups and used different methods of mutation screening and case ascertainment. Although the large sample size from the pooled trials allowed for an analysis of survival rates, the differences in study designs and populations “may limit the specificity of the conclusions.”

Bolton KL, Chenevix- Trench G, Goh C, et al. Association between BRCA1 and BRCA2 mutations and survival in women with invasive endothelial ovarian cancer. JAMA. 2012;307(4):382-389. doi:10.1001/jama.2012.20