Background: We previously showed that adding carboplatin to paclitaxel/liposomal doxorubicin (PM) can improve pCR rates in patients with TNBC at the cost of added toxicity (von Minckwitz, Lancet Oncology 2014). In this study we examine whether HRD, together with BRCA mutation in the primary tumor (tmBRCA), can predict pCR (ypT0/is ypN0). Methods: In GeparSixto, patients were randomized to receive PM or PM plus carboplatin stratified by subtype (TNBC, HER2+/HR-, HER2+/HR+) and Ki67 level. FFPE tumor samples with sufficient DNA were available in 193 (61.3%) out of 315 participants of GeparSixto with TNBC. TmBRCA and HRD scores (defined as the unweighted sum of LOH (Abkevich, 2012), TAI (Birkbak, 2012), and LST (Popova, 2012) scores) were determined. HR deficiency was defined as either a high HRD score (predefined with ≥ 42) or tmBRCA (HRD Positive). Results: Patients included in this analysis did not differ clinically from all study patients with TNBC in GeparSixto, except for Ki67 levels which were higher for patients included in the current analysis. HR deficiency was found in 136 (70.5%) tumors; 82 (60.3%) of them showed high HRD score without tmBRCA. HR deficient tumors were more likely to respond with a pCR (55.9%) than HR non-deficient tumors (29.8%; p = 0.001). Adding carboplatin to PM increased the pCR rate from 45.2% to 64.9% in HR deficient tumors (p = 0.025). The response rate in HR non-deficient patients was 20% and 40.7% in the PM vs PM plus carboplatin respectively and was not significant (p = 0.146). In patients with non-tmBRCA a high HRD score was associated with a higher pCR rate (49.4%) than a low HRD score (30.9%; p = 0.050) irrespective of the use of carboplatin. Conclusions: HR deficiency in TNBC as well as HRD score in non-tmBRCA TNBC are predictors of response to neoadjuvant anthracycline and taxane containing chemotherapy irrespective of the use of carboplatin with the highest response rate being in the HR-deficient group treated with carboplatin (pCR rate of 64.9%). HR deficiency may be used to identify patients likely to have a high response to DNA-damaging agents. Clinical trial information: NCT01426880.