Related Experiment Video
Updated: Sep 10, 2025
Author Spotlight: Investigating Immune Cell Dynamics in the Tumor Microenvironment — Challenges and Innovations in Cancer Prognosis
Published on: April 12, 2024
Prognostic Impact of Real-World Immunohistochemical Changes in Breast Cancer Treated with Neoadjuvant Chemotherapy
Marcelo Antonini1, André Mattar2, Marcelo Madeira3
1Hospital do Servidor Público Estadual Francisco Morato de Oliveira, São Paulo, São Paulo, Brazil; BBREAST Group - Brazilian Breast Association Team, São Paulo, São Paulo, Brazil.
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.
