Unveiling the Involvement of Extracellular Vesicles in Breast Cancer's Organotrophic Metastasis: Molecular Mechanisms and Translational Prospects.

Breast cancer metastasis remains the primary driver of patient mortality, involving dynamic interactions between tumor cells and distant organ microenvironments. In recent years, tumor cell-derived extracellular vesicles (EVs) have emerged as critical information carriers, playing central roles in breast cancer metastasis by mediating organ-specific pre-metastatic niche formation, immune modulation, and tumor cell adaptive evolution. Studies have demonstrated that EVs drive the metastatic cascade through the delivery of bioactive components, including nucleic acids (e.g., miRNAs, circRNAs), proteins (e.g., integrins, metabolic enzymes), and lipids, which collectively regulate osteoclast activation, immune cell polarization, vascular permeability alterations, and extracellular matrix (ECM) remodeling in target organs such as bone, the lungs, and the liver. Molecular heterogeneity in EVs derived from different breast cancer subtypes strongly correlates with organotropism, providing potential biomarkers for metastasis prediction. Leveraging the organotrophic mechanisms of EVs and their dual regulatory roles in metastasis (pro-metastatic and anti-metastatic), strategies targeting EV biogenesis, cargo loading, or delivery exhibits translational potential in diagnostics and therapeutics. In this review, we summarize recent advances in understanding the role of breast cancer-derived exosomes in mediating metastatic organotropism and discuss the potential clinical applications of targeting exosomes as novel diagnostic and therapeutic strategies for breast cancer.