Abstract Background BRCA1/2-associated triple-negative breast cancer (TNBC) is an aggressive BC subtype, yet it exhibits high chemosensitivity. Emerging evidence suggest that mitomycin C, either as a monotherapy or combined with platinum agents, demonstrates efficacy in BRCA1/2-driven carcinomas. This clinical trial aimed at comparison of mitomycin C-based versus standard neoadjuvant chemotherapy (NACT) in BRCA1/2-associated TNBC. Method The study included 52 BRCA1/2 pathogenic allele carriers diagnosed with T1-3N0-3M0 TNBC. Patients were divided into two groups: an experimental group (n = 26) that received four cycles of mitomycin C 10 mg/m2 plus carboplatin (AUC 5) followed by 12 cycles of weekly paclitaxel 80 mg/m2 (MCbP-T) and a control group (n = 26) that received four cycles of doxorubicin 60 mg/m2 plus cyclophosphamide 600 mg/m2 followed by 12 cycles of weekly paclitaxel 80 mg/m2 plus carboplatin (AUC 2) (AC-TCbP). Therapy efficacy was evaluated based on RECIST criteria and the rate of complete pathological response (pCR) upon surgery. Results Objective responses were recorded in all patients involved in the study. Clinical complete response was achieved in 18/26 (69%) and 15/26 (58%) patients in the MCbP-T and AC-TCbP arms, respectively (p = 0.57, Fisher’s exact test). In the MCbP-T arm, the frequency of pCR was 21/26 (81%). This was numerically but statistically non-significantly higher than that in the AC-TCbP group (16/26; 62%; p = 0.2, Fisher’s exact test). In the AC-TCbP arm, grade III leukopenia and neutropenia occurred in 11/26 (42%) and 12/26 (46%) patients, respectively. In MCbP-T arm, grade III leukopenia and neutropenia were documented in 1/26 (4%; p = 0.002, Fisher’s exact test) and 2/26 (8%; p = 0.003, Fisher’s exact test) patients, respectively. The frequency of thrombocytopenia of all grades was non-significantly higher in MCbP-T group. All patients in the control group had alopecia grade II, whereas patients in the MCbP-T group didn’t report this side effect. Conclusion In BRCA1/2-associated TNBC, the efficacy of MCbP-T regimen is comparable with standard anthracycline-based platinum-containing chemotherapy but demonstrates a significantly lower rate of adverse effects. Citation Format: D. ?. Enaldieva, P. V. Krivorotko. Mitomycin C plus carboplatin followed by paclitaxel vs. standard doxorubicin-cyclophosphamide followed by paclitaxel-carboplatin neoadjuvant therapy in BRCA1/2-associated breast cancer abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS4-07-20.
Enaldieva et al. (Tue,) studied this question.