Olaparib, a poly (ADP-ribose) polymerase (PARP) inhibitor (PARPi), is approved for the treatment of human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC) in germline (g) / mutation carriers. Olaparib Expanded, an investigator-initiated, phase II study, assessed olaparib response in patients with MBC with somatic (s) / mutations or g/s mutations in homologous recombination (HR)-related genes other than 2. Eligible patients had MBC with measurable disease and germline mutations in non- / HR-related genes (cohort 1) or somatic mutations in these genes or / (cohort 2). Prior PARPi, platinum-refractory disease, or progression on more than two chemotherapy regimens (metastatic setting) was not allowed. Patients received olaparib 300 mg orally twice a day until progression. A single-arm, two-stage design was used. The primary endpoint was objective response rate (ORR); the null hypothesis (≤ 5% ORR) would be rejected within each cohort if there were four or more responses in 27 patients. Secondary endpoints included clinical benefit rate and progression-free survival (PFS). Fifty-four patients enrolled. Seventy-six percent had estrogen receptor-positive HER2-negative disease. Eighty-seven percent had mutations in s / , or . In cohort 1, ORR was 33% (90% CI, 19% to 51%) and in cohort 2, 31% (90% CI, 15% to 49%). Confirmed responses were seen only with g (ORR, 82%) and s / (ORR, 50%) mutations. Median PFS was 13.3 months (90% CI, 12 months to not available/computable NA) for g and 6.3 months (90% CI, 4.4 months to NA) for s / mutation carriers. No responses were observed with or mutations alone. PARP inhibition is an effective treatment for patients with MBC and g or s / mutations, significantly expanding the population of patients with breast cancer likely to benefit from PARPi beyond g / mutation carriers. These results emphasize the value of molecular characterization for treatment decisions in MBC.