Extracellular vesicle–associated and non–vesicle-associated microRNAs for early breast cancer detection: a systematic review

Breast cancer remains a leading cause of morbidity and mortality worldwide, with survival outcomes strongly dependent on early detection. Conventional mammography, while widely adopted, faces limitations in sensitivity—particularly in dense breast tissue—and is not without invasiveness. Circulating microRNAs (miRNAs), both exosomal and non-exosomal, have emerged as promising non-invasive biomarkers due to their stability in biofluids and cancer-associated dysregulation. This systematic review evaluated studies published between 2016 and 2025 assessing the diagnostic performance of blood-derived miRNAs for early breast cancer detection. Several individual miRNAs, including miR-21-5p and miR-200c, as well as panels such as those comprising miR-106a-3p, miR-106a-5p, miR-20b-5p, and miR-92a-2-5p, demonstrated high diagnostic accuracy (Area Under the Curve (AUC) > 0.9) in distinguishing breast cancer patients from healthy controls. Despite challenges related to tumor heterogeneity and pre-analytical standardization, integrating circulating miRNA biomarkers with current imaging modalities holds significant potential to enhance early detection and support personalized management strategies.