Tumor-derived EV miRNA signatures surpass total EV miRNA in supplementing mammography for precision breast cancer diagnosis.

With the rising global incidence and mortality rates of breast cancer, early diagnosis is becoming increasingly crucial. The World Health Organization (WHO) recommends mammography as a primary screening tool. However, despite its clinical benefits, mammography has potential risks including radiation exposure, unnecessary follow-up, and overdiagnosis due to false positives, particularly in cases of early cancer or dense breast tissue. In this study, we aimed to address these concerns by introducing an innovative diagnostic method that employs circulating biomarkers to enhance the existing screening techniques Breast cancer-derived extracellular vesicles (BEVs) were isolated from the bloodstream using advanced immunoaffinity capture techniques. Subsequently, we analyzed the microRNA (miRNA) profiles of BEVs in plasma samples from 120 patients with breast cancer, 46 with benign tumors, and 45 healthy controls. This retrospective study identified a distinct signature of five EV miRNAs (miR-21, miR-106b, miR-181a, miR-484, and miR-1260b) that effectively differentiated patients with breast cancer from healthy controls. This signature provides essential insights into tumor progression, metastasis, and the risk of recurrence. Notably, overexpression of this signature correlated with poorer survival outcomes. Our novel gene signature-based approach not only complements existing diagnostic methods with high accuracy but also provides a deeper understanding of the molecular aspects of breast cancer, heralding a significant advancement in precision medicine and personalized cancer care.