Efficacy of dose-dense platinum-based neoadjuvant chemotherapy in patients with BRCA1/2-associated operable and locally advanced triple-negative breast cancer

Introduction . BRCA status is of interest as a predictive marker in the context of neoadjuvant chemotherapy (NACT). The goal of NACT in triple-negative breast cancer (TNBC) is to achieve a pathologic complete response (pCR), which is associated with a significant improvement in event-free and overall survival, and it influences further treatment strategy. The absence of a pronounced pathological response after NACT requires the administration of post-neoadjuvant therapy. Despite numerous studies, the optimal NACT regimen for this group of patients has not yet been determined. Objective . To evaluate the efficacy and tolerability of dose-dense platinum-based NACT (4 ddAC followed by 12 PCb) in patients with BRCA1/2- mutated TNBC in terms of pCR rate and Residual Cancer Burden (RCB) score, and to identify predictive factors of treatment efficacy. Materials and Methods . This prospective study included 103 patients with gBRCA1/2-associated stage II–III TNBC who received dose-dense platinum-based NACT between January 2018 and December 2024. Among them, 41.7 % had stage III disease and 26.2 % had lymph node involvement at levels N 2–3. Results . The overall pCR rate was 63.1 % (n=65), while disease progression was observed in 7.8 % (n=8). In operable cases, the pCR rate was 63.5 %, and in locally advanced inoperable cases, it was 62.5 %. The most common germline mutation in BRCA1/2 genes was BRCA1 c.5266dup, found in 53.4 % (n=55) of cases. Rare mutations detected by NGS accounted for 30 % (n=31), while common mutations identified by PCR comprised 70 %. Among patients with common mutations, the pCR rate was 70.8 %, compared to 45.2 % in those with rare mutations. The most frequent type of toxicity was hematologic: grade III–IV neutropenia occurred in 33 % (n=34). Dose reduction was performed only in cases of grade II–III adverse events. The only factor significantly associated with higher pCR rate was the presence of common germline BRCA1/2 mutations (p=0.027). Conclusions . Dose-dense NACT including anthracyclines, taxanes, and platinum agents achieves a high rate of pCR in patients with gBRCA1/2- associated stage II–III TNBC, particularly in those with common mutations. The presence of residual tumor after the full course of NACT indicates the need for personalized adjuvant targeted therapy with olaparib.

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