The study includes two groups: one is an experimental group receiving chemotherapy according to the MCarb-T regimen, which is compared to a control group treated with the standard AC-TCarb regimen. To participate in this study, patients must have histologically confirmed triple-negative breast cancer (TNBC) in a locally advanced stage and a germline BRCA1 or BRCA2 mutation. All patients with TNBC undergo BRCA1/BRCA2 mutation testing before starting treatment, using either polymerase chain reaction (PCR) or next-generation sequencing (NGS).
Patients in the experimental group receive 4 cycles of neoadjuvant chemotherapy with the MCarb regimen (mitomycin + carboplatin AUC5), followed by 12 weekly doses of paclitaxel. Patients in the control group receive 4 cycles of neoadjuvant chemotherapy with the AC regimen (doxorubicin + cyclophosphamide), followed by 12 weekly administrations of the TCarb regimen (paclitaxel + carboplatin AUC2).
Clinical assessment is performed after cycles 2 and 4 of MCarb/AC, as well as after completion of the 12 weekly doses of T/ TCarb, with response evaluation according to RECIST 1.1 criteria.
Upon completion of cytotoxic chemotherapy, patients undergo surgical treatment. Resected specimens are evaluated using the Miller-Payne grading system and the Residual Cancer Burden (RCB) classification to determine the efficacy of systemic therapy.
To assess the safety of neoadjuvant systemic therapy, the frequency and nature of adverse events are recorded during treatment using the NCI CTCAE version 5.0 criteria. As part of the study protocol, complete blood counts with differential and platelet counts (Fonio method) were performed every 7 days, while blood biochemistry, urinalysis, and coagulation tests were carried out every 14 days.
After completion of protocol therapy, patients were followed to assess disease status every 3 months during the first year and every 6 months thereafter. Monitoring included physical examination, ultrasound of the breasts and regional lymph nodes, mammography, contrast-enhanced computed tomography of the chest and abdomen, ultrasound or contrast-enhanced magnetic resonance imaging of the pelvis, and bone scintigraphy.
