Short-term Survival Advantage of Carrying BRCA Mutation Does Not Extend to Long Term

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While carrying a BRCA 1 or BRCA 2 mutation was associated with a better prognosis in the 3-year period after diagnosis of invasive ovarian cancer, this short-term survival advantage did not lead to long-term survival benefit, according to a study published in the Journal of the National Cancer Institute. The study followed 1,626 unselected women diagnosed with invasive ovarian cancer in Ontario, Canada, and Tampa, Florida, for a mean of 6.9 years (range, 0.3–15.7 years). Among these women, “129 were identified as carriers of BRCA1 mutations, 89 were identified as carriers of BRCA2 mutations, and 1,408 were classified as noncarriers,” the researchers reported. Overall, the mutation carriers made up 13.4% of the study population.

“The mutation carriers had an unfavorable distribution of stage, grade, and histology, compared with noncarriers and therefore an adjusted analysis was conducted,” the researchers reported. “In multivariable survival analysis, adjusted for histologic subtype, age at diagnosis, disease stage, and grade, the presence of a BRCA1 or BRCA2 mutation was associated with a better prognosis at 3 years after diagnosis (hazard ratio [HR] = 0.68, 95% confidence interval [CI] = 0.48–0.98; P = .03). The advantage waned over time; at 5 years after diagnosis, the hazard ratio was 0.79 (95% CI = 0.63–1.01; P = .06), and at 10 years after diagnosis, the hazard ratio was 1.00 (95% CI = 0.83–1.22; P = .90).

Women with serous cancers (73% of the BRCA mutation carriers and 53% of the nonhereditary cases) had worse survival than women with other histologic subtypes. Among women with serous cancers, 12-year survival (which the investigators deemed “a reasonable surrogate for cure”) was similar for BRCA1 mutation carriers (27.4%), BRCA2 mutation carriers (27.7%), and noncarriers (27.1%).

“We believe that there is insufficient evidence to conclude that survival from ovarian cancer differs between carriers and noncarriers, and we disagree with the recommendation that health-care providers should counsel women with ovarian cancer and carrying BRCA mutations that they should expect their survival to be better than that of noncarriers or that treatment could be tailored to reflect the differences in survival,” the authors concluded. ■

McLaughlin JR, et al: J Natl Cancer Instit 105:141-148, 2013.