Neoadjuvant response stratification based on complete, partial, and no response in HR-positive/HER2-positive breast cancer

Background: This study aimed to evaluate the prognostic relevance of stratified pathological response -complete response (CR), partial response (PR), and no response (NR)- to neoadjuvant chemotherapy (NAC) in patients with hormone receptor-positive and HER2-positive (HR + /HER2 +) breast cancer. Methods: A total of 8277 HR + /HER2 + breast cancer patients treated with NAC between 2010 and 2021 were retrospectively identified from the SEER database. Patients were categorized into CR, PR, and NR groups. Overall survival (OS) and disease-specific survival (DSS) were analyzed using Kaplan–Meier and Cox regression models. Results: CR, PR, and NR rates were 52.3%, 41.4%, and 6.2%, respectively. Five-year OS rates were 96.3% (CR), 91.1% (PR), and 79.3% (NR), while 10-year DSS rates were 94.0% (CR), 83.4% (PR), and 76.2% (NR) (p < 0.001). In multivariate analysis, PR and NR were associated with significantly increased mortality risk compared to CR (OS HR: 2.16 and 4.20; DSS HR: 2.95 and 5.46; all p < 0.001). Progesterone receptor (PrgR) negativity independently predicted worse OS and DSS, whereas ER status had no significant impact. Additional adverse prognostic factors included advanced age, nodal metastasis, rural residence, and mastectomy. Radiotherapy did not retain significance in multivariate models. Conclusion: Pathological response to NAC is a strong independent prognostic marker in HR + /HER2 + breast cancer. Partial responders represent a clinically distinct group with intermediate outcomes, highlighting the need for response-adapted therapeutic strategies beyond conventional staging systems.