Circulating microRNAs at the Interface of Obesity and Breast Cancer: From Molecular Machinery, Diagnostic Potential, and Therapeutic Perspectives.

Obesity influences breast cancer risk, progression, and therapeutic response through endocrine, inflammatory, metabolic, stromal, and vesicular mechanisms. Circulating and extracellular vesicle (EV)-associated microRNAs are attractive liquid biopsy candidates; however, in obesity-associated breast cancer, they should not be interpreted as tumor-only biomarkers. This narrative review analyzes circulating/EV-miRNAs as mixed host-tumor signals and separates association-based biomarker evidence from functional EV-mediated transfer. We performed a narrative and integrative review of studies on miRNA biogenesis, circulating miRNA transport, EV biology, adipose tissue dysfunction, adipose-tumor communication, biomarker development, therapy response, and methodological reporting standards. The current literature is read along two independent axes: human relevance and source attribution, from non-breast models to obesity-stratified human cohorts, and mechanistic causality, from association only to EV-level function, miRNA-level function, and causality with rescue; clinical validation is treated as a separate qualifier rather than as the top of a single scale. For example, EV-let-7a in overweight/obese breast cancer patients mainly supports an obesity-stratified biomarker candidate. Breast adipose tissue-derived EV cargoes enriched in miR-155-5p, miR-10a-3p, and miR-30a-3p provide stronger functional support for metabolic reprogramming, whereas EV-associated miR-221/222 has mediator-level evidence in endocrine resistance but is not obesity specific. Conclusions: The main contribution of this review is an operational interpretation framework in which circulating miRNAs are evaluated according to probable source, evidence level, and clinical purpose. Future studies should report EV workflow quality, sample type, hemolysis and platelet control, normalization strategy, external validation, tumor subtype, and obesity phenotyping beyond BMI, including waist circumference or waist-to-hip ratio, insulin resistance, diabetes, menopausal status, and inflammatory markers.