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Abstract
Introduction. Breast cancers associated with germline BRCA1/2 mutations exhibit homologous recombination deficiency, resulting in increased sensitivity to DNA-damaging agents, including platinum compounds. However, the role of platinum-based neoadjuvant chemotherapy (NACT) in this specific patient population remains debated.
Aim. To evaluate the impact of incorporating platinum agents into NACT regimens on the rate of pathologic complete response (pCR) in patients with germline BRCA1/2-associated triple-negative breast cancer (TNBC).
Materials and Methods. This single-center study analyzed a prospectively maintained database with a retrospective control cohort. 232 patients with stage II–III BRCA1/2-associated TNBC who received NACT followed by surgery were included. Patients were stratified into two groups based on treatment regimen: platinum-containing anthracycline–taxane NACT (n=169) and platinum-free anthracycline–taxane NACT (n=63). The primary endpoint was pCR (RCB 0). Univariate logistic regression analysis was performed to estimate odds ratios (ORs) with 95% confidence intervals (CIs).
Results. The pCR rate was significantly higher in the platinum group compared to the non-platinum group (63.3% vs. 41.3%; OR 2.46, 95% CI 1.36–4.43; p=0.03). The benefit of platinum addition was most pronounced in patients with stage II disease (OR 2.63; p=0.008), those harboring common BRCA1/2 mutations (OR 2.67; p=0.013), and those receiving standard (non-dose-dense) AC regimens (OR 2.72; p=0.022). No statistically significant benefit was observed in patients with rare mutations or in those treated with dose-dense chemotherapy. In the subgroup with the most prevalent BRCA1 mutation (5382insC), the advantage of platinum did not reach statistical significance. In the weekly paclitaxel subgroup, a trend toward increased pCR was observed without reaching statistical significance (OR 2.04; p=0.051).
Conclusion. The incorporation of platinum agents into NACT regimens for patients with BRCA1/2-associated TNBC is associated with a significantly higher pCR rate. The magnitude of benefit varies across clinical and molecular subgroups, underscoring the need for further treatment individualization. These findings require validation in larger prospective studies.
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