Breast cancer brain metastasis (BCBM) is driven by microenvironmental remodeling across three interconnected phases: the primary tumor microenvironment (TME) licenses dissemination, the pre-metastatic niche (PMN) primes the brain, and the established metastatic niche sustains outgrowth through central nervous system (CNS)-resident cell interactions. These phases are individually established; we integrate them through cross-phase signaling axes, exemplified by the proposed IL-6$\rightarrow$extracellular vesicle (EV)$\rightarrow$blood-brain barrier (BBB) disruption cascade, that link tumor-associated macrophage-driven epithelial-mesenchymal transition to PMN conditioning and niche maintenance.... More >