Androgen receptor expression in breast cancer brain metastases

Abstract

Background: Brain metastases (BM) are a particular clinical challenge occurring frequently in breast cancer patients and are associated with decreased survival due to the limited treatment options. Androgen receptor (AR) expression is an emerging therapeutic target in breast cancer as it is frequently expressed in the luminal A and B breast cancer (BC) subtypes and further in approximately one-third of basal-like cancers. As AR-positive BC displays a distinct biological behavior, we aimed to analyze AR expression in the particular context of breast cancer BM. Methods: Patients with newly diagnosed breast cancer BM treated with neurosurgical resection were identified from the Vienna Brain Metastasis Registry and clinical data including patient characteristics, biological tumour subtypes and overall survival (OS) were obtained by retrospective chart review. Formalin fixed and paraffin embed tumour block containing viable BM tissue were retrieved from the Neuro-Biobank. Immunohistochemical staining of AR was performed and AR expression in the tumor nucleus was evaluated. Results: 46 BM samples from 46 individual patients with breast cancer were available for this analysis. AR expression of≤1% was evident in 15/46 (32.6%) BM specimens and median AR-expression rate was 1% (range 0-60). A non-significantly higher rate of AR expression in≤1% tumor cells and breast cancer subtype was evident as 9/18 (50.0%) BM of the luminal subtype, 4/16 (25.0%) of the HER2-positive subtype and 2/ 12 (16.7%) of triple-negative subtype specimens expressed AR (p>0.05). Median brain metastases-free survival (BMFS) was 30 months (range 0-210). No association with BMFS and BM AR expression was evident (HR 1.0; 95% CI 1.0-1.0; p>0.05). Median survival from diagnosis of BMwas 9 months (range 0-104) in the entire cohort. No association of survival prognosis and AR expression ≤1% was evident (9 vs 10 months; HR 1.0; 95% CI 1.0-1.0; p>0.05; log rank test). Conclusions: According to our sample analysis, AR is expressed in one third of breast cancer brain metastases with the highest rates among the luminal breast cancer subtype and therefore might be a potential treatment target in the particular population of breast cancer patients with BM for future clinical investigation.