Clinicopathological Predictors of Pathological Complete Response in HER2-Positive Breast Cancer Treated with Pertuzumab-Based Neoadjuvant Therapy: A Multicenter Real-World Study

Background and Objectives: Neoadjuvant systemic therapy incorporating dual HER2 blockade has significantly improved outcomes in patients with HER2-positive breast cancer. Pathological complete response (pCR) is an important surrogate endpoint associated with improved long-term survival. However, substantial heterogeneity in treatment response persists, and identifying factors associated with pCR remains clinically relevant. In addition to established clinicopathological variables, systemic inflammation-based biomarkers have recently been investigated as potential predictors of treatment response. Materials and Methods: In this multicenter retrospective study, we evaluated patients with stage II–III HER2-positive breast cancer who received pertuzumab-based neoadjuvant therapy followed by surgery between January 2023 and June 2025 across six oncology centers in Türkiye. Clinicopathological characteristics, treatment-related variables, and baseline systemic inflammation-based biomarkers were analyzed. Logistic regression analyses were performed to identify factors associated with pCR. Results: A total of 372 patients were included, and the overall pCR rate was 61%. Higher pCR rates were observed in patients with hormone receptor-negative tumors (71.4% vs. 54.3%, p = 0.001) and in premenopausal patients (68.7% vs. 53.4%, p = 0.003). In multivariate analysis, hormone receptor status (OR 2.25, 95% CI 1.41–3.60, p < 0.001), menopausal status (OR 1.90, 95% CI 1.22–2.94, p = 0.005), neoadjuvant treatment regimen (OR 2.15, 95% CI 1.05–4.41, p = 0.037), and perineural invasion (OR 2.61, 95% CI 1.10–6.22, p = 0.030) were independently associated with pCR. In contrast, systemic inflammation-based biomarkers did not demonstrate significant associations with pCR, and ROC analyses showed limited discriminatory ability (AUC values approximately 0.5). Conclusions: In patients with HER2-positive breast cancer treated with pertuzumab-based neoadjuvant therapy, treatment response appears to be primarily influenced by clinicopathological and treatment-related factors rather than systemic inflammatory status. Peripheral blood inflammatory biomarkers derived from routine laboratory parameters showed limited value in predicting pCR in this setting.