Prognostic impact of endocrine therapy and BDNF-TrkB axis in breast cancer brain metastases.

purposeWe aimed to delineate strategies for improved management of brain metastases (BM) in breast cancer by investigating the estrogen-related BDNF–TrkB pathway within the tumor microenvironment.

methodsSurgical specimens of BM tissues from breast cancer patients were analyzed using multiplex immunohistochemistry. Expression patterns of BDNF, TrkB, and phospho-AKT were assessed separately in tumor and stromal compartments and compared across molecular subtypes. Clinical data were reviewed to identify factors associated with brain-specific progression-free survival (BPFS) and overall survival (BOS).

resultsEndocrine therapy following BM diagnosis was independently associated with prolonged brain-specific survival among luminal patients (HR for BPFS and BOS, 0.22 and 0.19; p = 0.002 and p < 0.001). Local treatments, including craniotomy, SRS, or WBRT, were also associated with improved BOS, whereas leptomeningeal spread and multiple lesions predicted poorer outcomes. Tumoral BDNF–TrkB–phospho-AKT co-expression was positively correlated with ERα expression (ρ = 0.544, p = 0.009), while stromal BDNF expression was related to luminal tumor status.

conclusionsSurvival after BM was influenced by both tumor characteristics and treatment modalities. In luminal disease, endocrine therapy and estrogen depletion may exert anti-tumor activity through inhibition of the BDNF–TrkB pathway. These findings provide novel insight into the biology of breast cancer brain metastases and suggest a rationale for further validation in multicenter studies. CLINICAL TRIAL NUMBER: Not applicable.