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Editor's Note
June 2015

Adjuvant Oophorectomy in the Treatment of Early-Stage BRCA Mutation–Positive Breast Cancer

JAMA Oncol. 2015;1(3):313. doi:10.1001/jamaoncol.2015.0708

The US Preventive Services Task Force recently released a systematic review focused on the risk of breast and ovarian cancer in BRCA1 and BRCA2 mutation carriers and the impact of genetic testing and counseling on the patient.1 A meta-analysis of 70 studies demonstrated that breast cancer prevalence was 46% to 71% by 70 years of age for those with BRCA1 or BRCA2 mutations and ovarian cancer prevalence was 41% to 46% for BRCA1 and 17% to 23% for BRCA2 mutation carriers. Patients with germline mutations in the BRCA gene family often choose prophylactic surgery, mastectomy and/or oophorectomy, to reduce their risk of developing breast or ovarian cancer. In this issue of JAMA Oncology, Metcalfe et al2 evaluated the impact of oophorectomy on overall survival of patients who have already received a diagnosis of breast cancer. The participants were 676 patients with stage I or II breast cancer and BRCA1 or BRCA2 mutations. Smaller studies have suggested that oophorectomy after a breast cancer diagnosis results in reduced mortality in these individuals at extreme genetic risk. The cohort reported by Metcalfe et al2 did or did not have their ovaries removed and were observed for 20 years to monitor for recurrence. The results provide a validation of the role of oophorectomy in conveying both a disease-free and overall survival benefit for BRCA1 mutation carriers. Oophorectomy after the primary diagnosis of breast cancer significantly reduced breast cancer–specific mortality in women with BRCA1 mutations (HR, 0.38 [95% CI, 0.19-0.77]; P = .007) but not in BRCA2 mutation carriers (HR, 0.57 [95% CI, 0.23-1.43]; P = .23). In the entire group, oophorectomy was particularly effective for survival benefit in women with estrogen receptor–negative breast cancer (HR, 0.07 [95% CI, 0.01-0.51]; P = .009). Of note, the mean time elapsed before oophorectomy after the diagnosis of breast cancer was 6.1 years. The hazard ratio was further reduced, however, if the surgery was performed within 2 years of the breast cancer diagnosis. The data reported here are compelling and suggest that the potential of oophorectomy should become part of the treatment discussion at the time of diagnosis for BRCA mutation carriers with early-stage breast cancers.

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Conflict of Interest Disclosures: Dr Disis reports receiving research grant funding from Seattle Genetics, EMD Serono, and VentiRx and holding stock options in VentiRx and EpiThany. No other disclosures are reported.

References
1.
Nelson  HD, Fu  R, Goddard  K,  et al.  Risk Assessment, Genetic Counseling, and Genetic Testing for BRCA-Related Cancer: Systematic Review to Update the US Preventive Services Task Force Recommendation. Rockville, MD: Agency for Healthcare Research and Quality; 2013.
2.
Metcalfe  K, Lynch  HT, Foulkes  WD,  et al.  Effect of oophorectomy on survival after breast cancer in BRCA1 and BRCA2 mutation carriers [published online April 23, 2015].  JAMA Oncol. doi:10.1001/jamaoncol.2015.0658.
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