Background: DNA copy number profiles identify patients with a defect in BRCA1 associated with a homologous recombination DNA repair defect. We previously showed that patients with a BRCA1-like profile benefit from high-dose (HD) and tandem HD chemotherapy (CT) (carboplatin/thiotepa/cyclophosphamide; ifosfamide/epirubicin/carboplatin). WSG AM-01 trial reported superiority of tandem HD vs. dose-dense CT in high-risk BC patients. Subgroup analysis attributed this effect to triple-negative BC. Methods: Phase III WSG AM-01 trial randomized 403 patients with >9 positive lymph nodes to 2xEC q2w followed by tandem HD (epirubicin/cyclophosphamide, thiotepa) or DD 4xEC --> 3xCMF q2w CT. Tumor CN profiles from 98 patients were generated with high-throughput sequencing and classified as BRCA1-like or non-BRCA1-like. Correlations with prognostic factors were assessed and Cox regression was done to investigate predictive/prognostic impact of BRCA1-like status on event free survival (EFS). Results: 17 of 94 (18%; HD/DD: 10 (19%)/7 (17%)) patients had BRCA1-like profiles. BRCA1-like status associated with high tumor grade (p=0.005) and triple-negative status (p<0.001). In multivariate Cox analysis for EFS, only age <50 years entered (HR=1.9, p=0.02) as a main effect. In subgroup analysis, only BRCA1-like status predicted for efficacy of HD. HR=0.26 (95% CI: 0.07-0.94, p=0.04) for BRCA1-like vs. 0.76 (95% CI: 0.43-1.34; p: 0.35) for non-BRCA1 like. In exploratory Cox interaction analysis (backward elimination) with BRCA1-like status, therapy and their interaction, the model retained BRCA1 status (HR=2.25; 95% CI: 1.07-5.94) and the predictive interaction BRCA1*therapy (HR=0.22; 95% CI: 0.06-0.79). Conclusions: Retrospective analysis suggests that superiority of rapidly cycled tandem HD alkylating over standard dose-dense CT in high-risk BC is substantially attributable to BRCA1-like (rather than TN) status. Comparing with other studies, this effect seems less drug-specific and indicates rather higher sensitivity of BRCA1-like tumors to any HD alkylating CT. The results will be validated in the prospective WSG ADAPT TN trial.