Background <p>Breast cancer (BC) remains a leading cause of malignancy-related deaths in women. underscoring the need for low-cost, fast, sensitive and non-invasive biomarkers. MicroRNAs as a critical regulators of gene expression, with distinct expression profiles linked to tumor genesis. Particularly miR-let7a-5p and miR-34a-5p are circulating molecules with key roles in tumor suppression and proliferation, offering significant diagnostic potential.</p> Objectives <p>This exploratory study investigated the expression levels of circulating miRNAs in breast cancer patients and healthy groups and assessed their potential utility as non-invasive diagnostic biomarkers for breast cancer.</p> Methods <p>200 serum samples were used in this analysis, the amount of each miR expression was measured using RT-qPCR and the fold changes were determined by 2^-ΔΔCt. P-values were determined by the t-test. ROC analysis demonstrated significant diagnostic accuracy to identify BC patients.</p> Results <p>Our findings indicate that circulating miR-34a-5p and miR-let-7a-5p are significant non-invasive breast cancer biomarkers, both being notably down-regulated in BC patients compared to healthy controls. With lower expression (fold change 0.503 vs. 0.810), superior diagnostic accuracy (AUC 0.8232) and higher (sensitivity 84%), miR-34a-5p outperformed let-7a-5p. No statistically significant association was identified between the studied miRNAs and age, BMI, or ER expression; however, miR-34a-5p demonstrated a weak negative correlation with PR.</p> Conclusion <p>Both circulating miR-34a-5p and let-7a-5p are significantly down-regulated in BC patients. MiR-34a-5p showed better accuracy on diagnostic performance, indicating its possible value as a promising non-invasive biomarker for the detection of breast cancer. This study explores the potential of these miRs in developing cost-effective strategies for breast cancer detection and risk assessment, monitoring and classification.</p>