BRCAness-Driven Prognostic Model and Regimen-Specific Therapeutic Implications in Triple-Negative Breast Cancer With Residual Disease After Neoadjuvant Chemotherapy.

Abstract

BRCAness, a phenotype associated with homologous recombination deficiency, has not been fully characterized in triple-negative breast cancer (TNBC) with residual disease after neoadjuvant chemotherapy (NAC), especially regarding prognosis and regimen-specific postoperative management. We analyzed 137 patients with TNBC who had residual invasive disease after NAC. BRCAness status was assessed in surgical specimens using multiplex ligation-dependent probe amplification (MLPA). Its associations with clinicopathological features and survival were evaluated according to NAC regimen, and prognostic models for disease-free survival (DFS) and overall survival (OS) were developed by combining BRCAness with clinicopathological variables. BRCAness was identified in 42.3% of tumors and was associated with high histological grade, high Ki-67, and perineural invasion. Patients with BRCAness-positive tumors had worse survival than those with BRCAness-negative tumors (5-year DFS, 50.0% vs. 68.2%, p = 0.020; 5-year OS, 58.6% vs. 78.1%, p = 0.014). This prognostic effect was evident in patients treated with anthracycline-based NAC, but not in those treated with platinum-based regimens. Models incorporating BRCAness showed good discrimination (DFS C-index, 0.70; 95% CI, 0.62-0.78; OS C-index, 0.75; 95% CI, 0.69-0.81). Among BRCAness-positive patients who had received anthracycline-based NAC, adjuvant chemotherapy was associated with better survival (5-year DFS, 55.6% vs. 27.3%, p = 0.035; 5-year OS, 66.7% vs. 36.4%, p = 0.023). BRCAness was associated with poorer outcome in residual TNBC after NAC and may help identify patients with different prognoses and postoperative treatment patterns.