Pathologic complete response after neoadjuvant chemotherapy for HER-2 negative breast cancer with HRR mutation.

Aims: This study compared pathologic complete response (pCR) rates to neoadjuvant chemotherapy (NAC) in HER2-negative early breast cancer patients with versus without homologous recombination repair (HRR) mutation, focusing on BRCA1/2.

Methods: This retrospective cohort study included HER-2-negative breast cancer patients who completed HRR genetic testing and received NAC. The primary endpoint was the pCR rate among HRR mutation carriers and noncarriers.

Result: Among 211 HER2-negative breast cancer patients analyzed, 64 (30.3%) harbored pathogenic/likely pathogenic HRR mutations, predominantly in BRCA1 (42.2%), BRCA2 (31.3%), and other HRR genes (26.6%). Hormone receptor positive patients accounted for 55.9% (118/211). Half of the patients (51.2%) treated with platinum-containing regimens. pCR rates were comparable between HRR mutation carriers and noncarriers (26.6% vs. 24.5%, p = 0.750), regardless of hormone receptor status. However, BRCA1 carriers achieved significantly higher pCR rates than BRCA2 carriers (40.7% vs. 10.0%, p = 0.001). Platinum-containing regimens (51.2% of patients) yielded greater benefit in BRCA1 carriers (pCR 61.1% vs. 12.5% in BRCA2; p = 0.022).

Conclusion: These data indicated that HRR mutations had no effect on pCR in HER-2 negative patients receiving NAC regardless of hormone receptor status. BRCA1 mutation carriers have a higher rate of pCR and are more benefit from platinum-containing regimen than BRCA2 mutation carriers.