Reassessing Treatment Response Stratification in HER2-Positive Breast Cancer

Background In HER2-positive breast cancer, response to neoadjuvant chemotherapy (NAC) is a key prognostic factor. While complete response (CR) is associated with improved survival, non-complete responses are typically treated as a homogeneous group in prognostic models. However, this binary classification may obscure clinically relevant differences, particularly for patients achieving partial response (PR). Methods We conducted a retrospective cohort study using a large national cancer registry to evaluate outcomes of HER2-positive female patients treated with NAC. Patients were classified into three groups based on treatment response: CR, PR, and no response (NR). Overall survival (OS) and disease-specific survival (DSS) were assessed using Kaplan–Meier analysis and multivariable Cox regression models adjusted for demographic, clinical, and treatment-related variables. Results Among 4711 patients, 72.4% achieved CR, 24.9% PR, and 2.8% NR. Both OS and DSS were significantly higher in the PR group compared to the NR group (10-year OS: 74.7% vs 35.5%, P < .001). In multivariate analysis, PR was independently associated with better survival than NR (HR for OS: 2.51; HR for DSS: 2.75; both P < .001). Other independent predictors of poor survival included older age, higher T/N stage, unmarried status, and absence of surgery. Conclusion A tripartite classification of treatment response—CR, PR, and NR—provides improved prognostic discrimination in HER2-positive breast cancer compared to the conventional binary model. Recognizing partial responders as a distinct clinical group may improve risk stratification and guide individualized treatment planning in the post-neoadjuvant setting.