Overview of MicroRNA Expression in Predicting Response to Neoadjuvant Therapies in Human Epidermal Growth Receptor-2 Enriched Breast Cancer – A Systematic Review

Purpose: Increased appreciation of the human epidermal growth factor receptor-2 (HER2/neu) signalling pathway has led to the development of targeted therapeutic agents used in conjunction with chemotherapy to improve outcomes for HER2 overexpressing (HER2+) breast cancer. For neoadjuvant therapy, response rates can be unpredictable – novel biomarkers predicting effectiveness are required to enhance oncological outcomes for these patients, and microRNA may prove effective. Our objective was to identify microRNA (miRNA) expression patterns predictive of response to neoadjuvant chemotherapy (NAC) and/or anti-HER2 targeted therapies in patients being treated for early-stage HER2+ breast cancer. Methods: A search was performed of the PUBMED, SCOPUS, Web of Science, and EMBASE in accordance to Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. Results: Overall, 15 studies including 1335 patients were included. These studies highlighted an expression profile of 73 miRNA and their ability to predict tumour response to neoadjuvant therapies was correlated. Results from 11 studies were in relation to circulatory miRNA and 4 studies included data from tumour tissue. Overall, upregulation and downregulation of 41 miRNA and 29 miRNA, respectively, predicted differential response to neoadjuvant therapy. Expression levels of 3 miRNA (miR-21, miR-210, and miR-376c-3p) were inconclusive in predicting therapeutic response, while ‘aberrant’ expression of circulating miR-199a predicted pathological complete response (pCR) to NAC. Conclusions: This systematic review outlines expression patterns of a number of miRNA which correlate with response to NAC and/or anti-HER2 therapies. Future translational research evaluating predictive biomarkers of primary response to neoadjuvant therapy in HER2+ breast cancer may consider these results.