Adjuvant Olaparib for Patients with BRCA1- or BRCA2-Mutated Breast Cancer

New therapies are needed to reduce recurrence in patients with BRCA1 or BRCA2 germline mutation-associated early breast cancer. We conducted a phase 3, double-blind, randomized trial involving patients with human epidermal growth factor receptor 2 (HER2)-negative early breast cancer with BRCA1 or BRCA2germline pathogenic or likely pathogenic variants and high-risk clinicopathological factors who had received local treatment and neoadjuvant or adjuvant chemotherapy.  A total of 1836 patients underwent randomization. The 3-year invasive disease-free survival was 85.9% in the olaparib group and 77.1% in the placebo group (hazard ratio for invasive disease or death, 0.58; P<0.001). The 3-year distant disease-free survival was 87.5% in the olaparib group and 80.4% in the placebo group; hazard ratio for distant disease or death, 0.57; 99.5%). Olaparib was associated with fewer deaths than placebo (59 and 86, respectively) (hazard ratio, 0.68; P = 0.02); however, the between-group difference was not significant at an interim-analysis boundary of a P value of less than 0.01. Among patients with high-risk, HER2-negative early breast cancer and germline BRCA1 or BRCA2 pathogenic or likely pathogenic variants, adjuvant olaparib after completion of local treatment and neoadjuvant or adjuvant chemotherapy was associated with significantly longer survival free of invasive or distant disease than was placebo.