Extracellular Vesicles in Breast Cancer: Immunomodulation, Biomarkers, and Therapy

Extracellular vesicles (EVs) are key mediators of intercellular communication within the tumor microenvironment (TME). In this narrative review, we synthesized relevant studies identified through a systematic search of PubMed and Web of Science (2020-2026), using search terms including "EVs", "breast cancer", "tumor microenvironment", "biomarkers", "macrophages", "fibroblasts", "T cells", and "therapy". Priority was given to peer-reviewed original research and recent high-quality reviews, with study selection based on relevance to EV biology, clinical translation, and methodological rigor. We first outline the potential roles of EVs in breast cancer pathogenesis, including their contribution to an immunosuppressive microenvironment, their regulatory effects on neighboring cells within the TME, and their promotion of malignant phenotypes in epithelial and vascular endothelial cells. Next, we outline studies on EV-based applications for early detection and prognostic stratification. Finally, we introduce emerging EV-related therapeutic strategies-such as adjuvant immunotherapy, stem cell-derived EVs, and engineered EVs-which remain primarily preclinical and face challenges including the lack of standardized isolation and characterization protocols, as well as unresolved issues regarding dosing, safety, and production. EVs are not yet established therapeutic tools; rather, they represent promising but unproven candidate therapies, with most clinical studies focusing on diagnostic applications. Through a narrative and critical review of the relevant literature, this review aims to advance the translation of EV research into more rigorous and practical applications for breast cancer diagnosis and treatment.