Micro-RNA 34a: Predictive Non-Invasive Biomarker for Detecting Neoadjuvant Chemotherapy Response in Egyptian Females with Breast Cancer

Abstract

Background: Breast cancer is the most prevalent malignancy among women globally. Neoadjuvant chemotherapy (NACT) improves surgical outcomes, yet reliable non-invasive biomarkers to predict treatment response remain limited. MicroRNAs (miRNAs) have emerged as promising molecular markers. MiR-34a, a tumor suppressor miRNA, has been linked to treatment response in breast cancer. Aim: To evaluate the potential utilization of circulating microRNA-34a (miR-34a) as a non-invasive biomarker for predicting NAC response in Egyptian females with breast cancer. Methods: This observational cross-sectional study included 40 pathologically confirmed breast cancer patients indicated for NAC at Cairo University Hospitals (June 2023–October 2024). Cases were indicated for 6 cycles of taxane-based NAC. Blood samples have been gathered at baseline (C0) and after two cycles (C2). Serum miR-34a expression has been determined using quantitative real-time PCR and normalized to miR-16. Clinical and pathological responses were assessed using RECIST criteria and post-surgical histopathology. Results: A complete response was achieved in 12/40 (30%) patients. Overall, miR-34a expression showed no significant change between C0 and C2 (p>0.05). However, subgroup analyses revealed significant associations. ER-negative complete responders had higher baseline miR-34a expression compared with non-responders (p=0.014). Among PRnegative patients, complete responders showed significantly higher baseline miR-34a than non-responders (p=0.028). In the Luminal B subtype, complete responders demonstrated significant downregulation of miR-34a after therapy (p=0.046). Conclusion: Dynamic changes in circulating miR-34a, particularly in ER-negative, PR-negative, and Luminal B subgroups, can act as a potential non-invasive biomarker for predicting NAC response in Egyptian BC patients.