Exercise-responsive microRNA networks and extracellular vesicle-mediated microRNA signaling in breast cancer: linking tumor signaling, systemic crosstalk, and clinical relevance.

Breast cancer is increasingly recognized as a systemic disease shaped by dynamic interactions between tumor-intrinsic signaling and host physiology. MicroRNAs (miRNAs), as post-transcriptional regulators, extend beyond canonical gene silencing to coordinate oncogenic pathways, tumor microenvironment remodeling, and inter-organ communication. In parallel, exercise has emerged as a systemic modulator capable of influencing immune, metabolic, and circulatory processes relevant to tumor progression. This review integrates current evidence on the interplay between miRNAs and exercise in breast cancer. We examine how miRNA-mediated networks regulate key processes including oncogenic signaling, angiogenesis, hypoxia responses, immune modulation, and metabolic adaptation. Particular attention is given to circulating and extracellular vesicle-associated miRNAs as mediators of systemic signaling, including muscle-tumor crosstalk. Emerging clinical data further support the role of circulating miRNAs as minimally invasive biomarkers for early detection and diagnosis, risk stratification, and monitoring of treatment response, with growing relevance to physical activity, overall health status, and lifestyle-based interventions that integrate exercise and behavioral modification strategies. Overall, this review proposes a systems-oriented framework in which miRNAs may link exercise-induced physiological adaptation to breast cancer biology, providing a foundation for future translational and precision oncology strategies.