Immunohistochemical changes after neoadjuvant chemotherapy and their impact on breast cancer survival: a systematic review and meta-analysis

Abstract

Changes in immunohistochemical (IHC) profiles following neoadjuvant chemotherapy (NAC) may impact therapeutic decisions and prognosis in breast cancer patients. However, the clinical significance of these biomarker conversions remains uncertain. To evaluate the frequency of IHC marker conversion (estrogen receptor [ER], progesterone receptor [PR], and HER2) after NAC and its association with pathological complete response (pCR), overall survival (OS), and disease-free survival (DFS). We conducted a systematic review and meta-analysis of cohort studies reporting pre- and post-NAC IHC profiles in breast cancer. A comprehensive search was performed in PubMed, Embase, Scopus, and Web of Science. The ROBINS-I tool was used to assess risk of bias. Random-effects models were applied to calculate pooled conversion rates and assess the prognostic impact of IHC changes. Twenty-four studies (n = 5891 patients) were included. The pooled conversion rates were 9.2% for ER, 15.1% for PR, 8.6% for HER2. Loss of hormone receptor positivity was associated with a lower pCR rate and worse DFS (HR 1.42; 95% CI, 1.11-1.81). HER2 gain correlated with improved pCR. High heterogeneity was observed, and sensitivity analyses confirmed the robustness of the results. IHC profile changes after NAC are frequent and clinically relevant. Loss of hormone receptor expression may indicate poorer prognosis, while HER2 gain suggests improved treatment sensitivity. Reassessment of IHC markers post-NAC should be considered to optimize adjuvant therapy decisions.