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.