Prognostic impact of real-world immunohistochemical changes in breast cancer treated with neoadjuvant chemotherapy

Abstract

Purpose To evaluate the rate and types of immunohistochemical (IHC) changes after neoadjuvant chemotherapy (NAC) and their influence on disease-free survival (DFS) and overall survival (OS) in breast cancer patients, with a focus on conversions such as HR+/HER-2+ to HR-/HER-2- and their implications for treatment adjustments. Methods This retrospective cohort study included 369 female patients aged 18 years or older with nonmetastatic breast cancer treated with NAC between January 2011 and January 2023. Patients who did not achieve complete pathological response were evaluated for changes in IHC profiles, including hormone receptor (HR) status, HER-2 expression, and Ki-67 index. Prognostic outcomes were assessed using Kaplan-Meier survival analysis and multivariate Cox regression models. Results IHC changes were observed in 41.7% of patients. Among those initially classified as HR-/HER-2-, 50.9% gained HR expression, and 14.1% acquired HER-2 expression. In HR+/HER-2+ cases, 70.8% experienced a loss of HER-2 expression. Patients with HER-2+ tumors exhibited more frequent IHC changes compared to HER-2- cases (P < .0001). After a median follow-up of 47.7 months, local recurrences occurred in 10.3% of patients, distant metastases in 29.5%, and 25.5% had died. Patients with IHC changes demonstrated significantly worse DFS and OS (P = .002), with the poorest outcomes associated with conversion to HR-/HER-2- (P < .001). Conclusion Post-NAC IHC changes are common and associated with poor prognosis, especially in patients losing HR and HER-2 expression. Monitoring IHC shifts is critical for guiding personalized treatment and improving prognostic evaluation.