The Promise of Immunotherapy for Breast Cancer Brain Metastases

Purpose of Review The goal of our review is to describe the rationale for immunotherapy in the treatment of breast cancer brain metastases (BCBM), the current landscape of clinical trials for this disease process, and possible future directions based on anticipated results. Recent Findings Immune checkpoint inhibition has shown efficacy in the treatment of several solid tumor brain metastases (i.e., melanoma and non-small cell lung cancer), but data specific to BCBM is relatively sparse. Preclinical studies in BCBM have illustrated a lower immune content in the brain microenvironment measured by tumor-infiltrating lymphocytes (TILs) in brain metastases compared to primary tumors. Yet, improved outcomes are associated with higher TIL content in the BCBM, and strategies to understand and alter the complex brain immune microenvironment are needed. Summary of Findings Based on observations in the non-breast cancer setting and early results in advanced breast cancer, it is likely that novel, strategic combination immunotherapy strategies will be needed to yield meaningful outcomes for BCBM patients. Some exciting concepts underway include novel immunotherapy combinations, concurrent stereotactic radiosurgery, bi-specific antibody armed activated T cells, and HER2-chimeric antigen receptor T cells for leptomeningeal disease.