Background: Neoadjuvant therapy with dual human epidermal growth factor receptor 2 (HER2) blockade using trastuzumab and pertuzumab combined with chemotherapy is the standard of care for patients with locally advanced HER2-positive breast cancer. However, responses vary among patients, particularly based on hormone receptor (HR) status. This study aimed to evaluate the predictive value of HR status for achieving pathological complete response (pCR) in this patient population. Methods: We conducted a multicenter, retrospective cohort study of patients with stage II-III HER2-positive breast cancer who received neoadjuvant trastuzumab and pertuzumab plus chemotherapy between January 2018 and December 2022. The primary endpoint was the pCR rate (ypT0/is ypN0). Secondary endpoints included breast conservation surgery (BCS) rate, objective response rate (ORR), and safety. Multivariate logistic regression analyses were performed to identify independent predictors of pCR, adjusting for potential confounders including chemotherapy regimen type. Event-free survival (EFS) was analyzed using the Kaplan-Meier method. Results: A total of 293 patients were included in the final analysis, with 170 (58.0%) being HR-positive (HR+) and 123 (42.0%) being HR-negative (HR-). The overall pCR rate was 48.1%. Patients in the HR- group achieved a significantly higher pCR rate than those in the HR+ group (65.0% vs. 35.9%; P 20% (OR = 2.01, 95% CI: 1.15-3.48; P = 0.012), and negative nodal status (OR = 1.85, 95% CI: 1.07-3.20; P = 0.026) were independent predictors of pCR. Chemotherapy regimen type was not a significant predictor. At a median follow-up of 36 months, the HR- group showed a trend towards better EFS (P = 0.043). Conclusion: HR status is a strong and independent predictor of pCR in HER2-positive breast cancer patients receiving neoadjuvant dual blockade. Patients with HR-negative disease derive the most benefit from this regimen, highlighting the need for tailored therapeutic strategies to improve outcomes for the HR-positive subgroup.
Liu et al. (2026) studied this question.