Prognostic impact of endocrine therapy and BDNF-TrkB axis in breast cancer brain metastases.
📄 Abstract
We 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. Surgical 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). Endocrine 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; Survival 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. Not applicable. The online version contains supplementary material available at 10.1007/s11060-025-05393-3.