Presence of a germline BRCA1 and/or BRCA2 mutation (gBRCAm) may sensitize tumors to poly(ADP-ribose) polymerase (PARP) inhibition via inactivation of the second allele, resulting in gene-specific loss of heterozygosity (gsLOH) and homologous recombination deficiency (HRD). Here we explore whether tissue sample testing provides an additional route to germline testing to inform treatment selection for PARP inhibition. In this prespecified exploratory analysis, BRCA1 and/or BRCA2 mutations in blood samples (gBRCAm) and tumor tissue (tBRCAm) were analyzed from patients with human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer and known gBRCAm, enrolled in the phase III OlympiAD trial. The frequency and nature of tBRCAm, HRD score status HRD-positive (score ≥42) versus HRD-negative (score <42) using the Myriad myChoice® CDx test and rates of gsLOH were determined, and their impact on clinical efficacy (objective response rate and progression-free survival) was explored. Tissue samples from 161/302 patients yielded tBRCAm, HRD and gsLOH data for 143 (47%), 129 (43%) and 125 (41%) patients, respectively. Concordance between gBRCAm and tBRCAm was 99%. gsLOH was observed in 118/125 (94%) patients BRCA1m, 73/76 (96%); BRCA2m, 45/49 (92%). A second mutation event was recorded for two of the three BRCA1m patients without gsLOH. The incidence of HRD-negative was 16% (21/129) and was more common for BRCA2m (versus BRCA1m) and/or for hormone receptor-positive (versus triple-negative) disease. Olaparib antitumor activity was observed irrespective of HRD score. gBRCAm identified in patients with HER2-negative metastatic breast cancer by germline testing in blood was also identified by tumor tissue testing. gsLOH was common, indicating a high rate of biallelic inactivation in metastatic breast cancer. Olaparib activity was seen regardless of gsLOH status or HRD score. Thus, additional tumor testing to inform PARP inhibitor treatment selection may not be supported for these patients. •We investigated if there is a role for tumor testing in HER2-negative metastatic breast cancer with germline BRCA mutations.•Tumor testing was able to detect known germline BRCA mutations, with 99% concordance for tumor tissue and blood.•HRD scores were mostly high and gsLOH was >90%.•Olaparib activity was seen in the few tumors with low HRD scores or lacking LOH.•Additional measurement of genome instability and gene-specific LOH may not inform PARP inhibitor treatment selection.