Bone marrow adipose tissue: fueling breast cancer bone metastasis via pro-tumor mechanisms and novel therapeutic targets.

Bone metastasis remains a major source of morbidity and mortality in breast cancer. Bone marrow adipose tissue (BMAT) is an active but incompletely defined component of the metastatic niche. This review uses an evidence-tiered framework to integrate four questions: how bone marrow adipocytes exchange lipids and signals with tumor cells; which observations are specific to breast cancer in bone; how broader bone-microenvironment and cross-cancer findings inform biological plausibility; and whether anticancer therapy reshapes BMAT in ways that could influence residual disease. Direct breast cancer evidence supports colonization of adipocyte-rich human bone explants and links adipocyte-derived signals with tumor migration, whereas several metabolic, dormancy, immune, and senescence pathways remain supported mainly by animal, in vitro, or other-cancer studies. Tumor cells, rather than bone marrow adipocytes, can increase fatty-acid transport, activation, and oxidation in response to adipocyte-derived lipids. Chemotherapy and aromatase inhibition can increase marrow adiposity, alter stromal lineage commitment, and promote bone loss; however, a direct causal pathway from treatment-induced BMAT expansion to breast cancer persistence, resistance, or relapse has not been established clinically. Accordingly, we distinguish documented treatment effects from proposed tumor consequences and separate established bone-directed therapy from experimental BMAT-targeted approaches. This framework positions BMAT as a testable and potentially modifiable niche component while avoiding the assumption that all adipocyte-rich marrow states are uniformly pro-metastatic.