Neoadjuvant mitomycin C plus carboplatin followed by paclitaxel vs. standard doxorubicin–cyclophosphamide followed by paclitaxel–carboplatin in BRCA1/2-associated breast cancer.

Abstract

620 Background: Triple-negative breast cancer (TNBC) associated with BRCA1/2 mutations is an aggressive disease subtype characterized by high sensitivity to chemotherapy. Accumulating evidence suggests the efficacy of mitomycin C, both as monotherapy and in combination with platinum agents, in BRCA1/2-driven tumors. This clinical study aimed to compare mitomycin C–based chemotherapy regimens with standard neoadjuvant chemotherapy in patients with BRCA1/2-associated TNBC. Methods: A total of 52 patients with BRCA1/2 pathogenic variants and TNBC stage T1-3N0-3M0 were enrolled. Patients were randomized to an experimental arm (n=26) receiving mitomycin C (10 mg/m²) plus carboplatin (AUC 5) (MCbP) for four cycles followed by weekly paclitaxel (80 mg/m²) for 12 cycles (MCbP-T), or to a control arm (n=26) receiving doxorubicin (60 mg/m²) and cyclophosphamide (600 mg/m²) (AC) for four cycles followed by weekly paclitaxel (80 mg/m²) plus carboplatin (AUC2) for 12 cycles (AC-TCbP). Treatment efficacy was assessed according to RECIST criteria and the rate of pathological complete response (pCR) after surgery. Results: After four cycles of MCbP/AC, clinical complete response (cCR) was observed more frequently in the MCbP group compared with the AC group (58% vs 7.7%; p = 0.0002). Upon completion of neoadjuvant chemotherapy, cCR remained significantly higher in the experimental arm (65.4% vs 42%; p = 0.037). The pCR rate was 81% versus 62% (p = 0.12), while Miller–Payne grade V pathological response was achieved in 77% and 65% of patients, respectively (p = 0.084). During a 26-month follow-up, adverse events occurred in 3.8% of patients in the experimental group and 12% in the control group; one death was reported only in the AC-TCbP arm (p = 0.6). Grade III leukopenia and neutropenia were more frequent in the AC-TCbP group (42% and 46%) compared with MCbP-T (4% and 8%; p = 0.002 and p = 0.003, respectively). Thrombocytopenia of any grade occurred more frequently in the MCbP-T group (36% vs 0%; p < 0.001). Grade II alopecia was observed in all patients in the control group and in none of the MCbP-T patients (p < 0.001). Conclusions: In BRCA1/2-associated TNBC, the MCbP-T regimen demonstrates efficacy comparable to standard anthracycline-based chemotherapy with platinum agents, while providing a more favorable safety profile and a lower incidence of adverse events.