Objective: This study aimed to evaluate the pathological complete response (pCR) rates and predictors of pCR in human epidermal growth factor receptor-2 (HER2)-positive, high-risk locally advanced breast cancer (BC) patients treated with neoadjuvant pertuzumab and trastuzumab combined with chemotherapy in a real-world setting.
Materials and
Methods: A retrospective cohort analysis was conducted on 116 patients diagnosed between April 2015 and April 2021. Pathological response was assessed using the Miller-Payne grading system, with pCR defined as the absence of invasive tumor cells in the breast and axillary lymph nodes. Univariate and multivariate analyses were performed to identify predictors of pCR.

Results: The pCR rate was 71.6%, significantly higher than rates reported in pivotal trials. Patients achieving pCR had superior 3-year event-free survival (85% vs. 58%, hazard ratio [HR]: 0.42; *p*=0.002). Younger age (HR: 0.93, *p*=0.03), higher tumor grade (HR: 0.31, *p*=0.016), androgen receptor positivity (HR: 0.41, *p*<0.001), and right-sided tumors (HR: 0.23, *p*=0.026) were independently associated with pCR.

Conclusion: Dual HER2 blockade with pertuzumab and trastuzumab in neoadjuvant therapy yields high pCR rates and improved survival outcomes in HER2-positive BC. Tumor biology and location may influence treatment response, supporting personalized therapeutic strategies.