Simple SummaryIn recent decades, neoadjuvant chemotherapy has proven to be a viable therapeutic option, particularly in cases of high-risk early or locally advanced breast cancer, for reducing tumor size, improving surgical outcomes, and evaluating full histological responses. Thus, individualizing post-neoadjuvant therapy has the potential to enhance prognosis. However, individual responses to therapy and long-term prognosis remain highly unpredictable. The current scenario requires the identification of biomarkers that accurately forecast responses to neoadjuvant therapy and identify patients who will not benefit from standard regimens. Circulating microRNAs have emerged as potential non-invasive biomarkers for breast cancer management. However, discrepancies between different studies currently hamper the implementation of circulating microRNAs, as a significant biomarker, in clinical practice.AbstractThe potential role of circulating microRNAs (miRNAs) as biomarkers in breast cancer (BC) management has been widely reported. However, the numerous discrepancies between studies in this regard hinders the implementation of circulating miRNAs in routine clinical practice. In the context of BC patients undergoing neoadjuvant chemotherapy (NAC), the possibility of predicting NAC response may lead to prognostic improvements by individualizing post-neoadjuvant therapy. In this context, the present meta-analysis aims to clarify circulating miRNAs’ predictive role with respect to NAC response among BC patients. We conducted a comprehensive literature search on five medical databases until 16 February 2023. We pooled the effect sizes of each study by applying a random-effects model. Cochran’s Q test (p-level of significance set at 0.05) scores and I2values were assessed to determine between-study heterogeneity. The PROBAST (Prediction Model Risk of Bias Assessment Tool) tool was used to evaluate the selected studies’ risk of bias. Overall, our findings support the hypothesis that circulating miRNAs, specifically miR-21-5p and miR-155-5p, may act as predictive biomarkers in the neoadjuvant setting among BC patients. However, due to the limited number of studies included in this meta-analysis and the high degrees of clinical and statistical heterogeneity, further research is required to confirm the predictive power of circulating miR-21-5p and miR-155-5p.