Breast-to-Brain Metastasis: from Microenvironment to Plasticity

Abstract

Abstract: Purpose of Review: Brain metastasis is a significant cause of mortality in breast cancer patients and treatment options are limited. This article will focus on the dynamic intercellular communication between metastatic cancer cells, the tumor microenvironment, and neighboring brain cells to breach the brain’s defenses and promote tumor progression. Recent Findings: Recent advances have further elucidated how tumor cells traverse through the blood–brain barrier and implicated the blood–cerebrospinal fluid barrier as a potential entry point. Tumor cells once within the brain milieu utilize factors secreted by and dynamically reprogram neurons, glial cells, and infiltrating leukocytes for their own colonization and survival. Summary: Current research has illuminated key mechanisms metastatic breast cancer cells utilize to infiltrate the brain and assimilate in their new environment. New multimodal treatments are investigating not only chemotherapy and radiation that can target metastatic tumor cells, but also immune checkpoint inhibitor–based therapies to sensitize the immune microenvironment.