Circulating and Tissue MicroRNA Profiles Associated with Pathological Complete Response in HER2+ Breast Cancer: A Systematic Review

MicroRNAs (miRNAs) have emerged as promising biomarkers for treatment response prediction in breast cancer. However, the role of circulating and tumour-derived miRNAs in predicting pathological complete response (pCR) following neoadjuvant therapy in HER2-positive (HER2+) breast cancer remains incompletely defined. To systematically evaluate the association between miRNA expression profiles and pCR in HER2+ breast cancer undergoing neoadjuvant systemic therapy, including chemotherapy with HER2-targeted agents. A systematic review of PUBMED, EMBASE, SCOPUS, and WEB OF SCIENCE databases was performed according to PRISMA guidelines. Studies evaluating circulating or tumour-derived miRNAs associated with pCR following neoadjuvant therapy in HER2+ breast cancer were included. Methodological quality was assessed using the QUIPS tool. Nine studies involving 937 HER2+ breast cancer patients were included. Overall, 39 unique miRNAs and four circulating miRNA signatures were associated with pCR outcomes. Seven studies evaluated circulating miRNAs, while two assessed tumour-derived miRNAs. The increased expression of six circulating miRNAs, four circulating signatures, and seventeen tumour-derived miRNAs was associated with pCR. Conversely, the increased expression of eleven circulating miRNAs and five tumour-derived miRNAs was associated with residual disease and non-pCR. MiR-210 was the only miRNA associated with response across more than one study, with an increased expression associated with residual disease in both circulating and tumour-derived analyses. Several circulating and tumour-derived miRNAs demonstrate potential as predictive biomarkers of pCR following HER2-targeted neoadjuvant therapy. However, substantial heterogeneity and limited validation currently restrict clinical implementation. Future prospective multicentre studies using standardised methodologies are required to clarify the role of miRNA profiling in personalised treatment strategies for HER2+ breast cancer.