Publication

Abstract : This study aims to evaluate HER2 expression and hormonal receptor (ER/PR) concordance between primary breast tumors and matched brain metastases. Breast cancer patients with brain metastases recruited in a prospective study underwent surgery at both primary and metastatic sites were considered for analysis [CTRI/2022/01/039599]. The present analysis is an extension of the protocol with retrospective analysis from a prospective clinical trial dataset. Demographic, clinicopathologic, treatment, and immunohistochemistry (IHC) data were collected from the hospital information system. IHC concordance, molecular subtype classification, and survival functions were analyzed. Subgroup analyses were performed using overall survival and pairwise log-rank tests based on ER/PR and HER2 concordance status. Fifteen patients were analyzed (mean age, 50 years; left breast, n = 7). In the primary tumor, ER, PR, and HER2 were positive in 33.3%, 33.3%, and 40% respectively. IHC discordance between primary and brain metastases was observed in six patients (40%), and concordance in nine (60%). Molecular subtype discordance between the primary and metastatic sites was 100% for luminal A, 66% for luminal B, and 40% for TNBC. Although not statistically significant (p > 0.05), mean overall survival was higher in concordant cases (40.2 vs. 34.27 months; p = 0.72). PR and ER negativity in primary tumors converted to positivity in brain metastases in 50% and 10% of cases respectively. Additionally, 34% of HER2-negative primaries became HER2-positive in metastases. A 40% discordance rate was observed in ER/PR/HER2 status between primary and brain metastatic sites. Molecular subtype reclassification occurred in a significant proportion, underscoring the importance of reassessing receptor status in metastases for better therapeutic decision-making. Present findings are from a small sample cohort and need further validation from a larger cohort.