Cisplatin and paclitaxel are active in triple-negative breast cancer (TNBC). Despite different mechanisms of action, effective predictive biomarkers to preferentially inform drug selection have not been identified. The homologous recombination deficiency (HRD) assay (Myriad Genetics, Inc.) detects impaired double-strand DNA break repair and may identify patients with BRCA1/2-proficient tumors that are sensitive to DNA-targeting therapy. The primary objective of TBCRC 030 was to detect an association of HRD with pathologic response (RCB-0/1) to single-agent cisplatin or paclitaxel.This prospective phase II study randomized patients with germline BRCA1/2 wild-type/unknown stage I-III TNBC to 12 weeks of preoperative cisplatin or paclitaxel. The HRD assay was performed on baseline tissue; positive HRD was defined as a score >33. Crossover to an alternative chemotherapy was offered if there was inadequate response.139 patients were evaluable for response, including 88 (63.3%) who had surgery at 12 weeks and 51 (36.7%) who crossed over due to inadequate clinical response. HRD results were available for 104 tumors (74.8%); 74 (71.1%) were HRD positive. RCB-0/1 rate was 26.4% with cisplatin and 22.3% with paclitaxel. No significant association was observed between HRD score and RCB response to either cisplatin (odds ratio [OR] for RCB 0/1 if HRD positive 2.22 [95% CI: 0.39-23.68]), or paclitaxel (OR for RCB 0/1 if HRD positive 0.90 [95% CI: 0.19-4.95]). There was no evidence of an interaction between HRD and pathologic response to chemotherapy.In this prospective preoperative trial in TNBC, HRD was not predictive of pathologic response. Tumors were similarly responsive to preoperative paclitaxel or cisplatin chemotherapy.