Dynamics of circulating microRNAs as a novel indicator of clinical response to neoadjuvant chemotherapy in breast cancer

Background: Circulating microRNAs (miRNAs) have been indicated as predictive biomarkers in breast cancer. We aimed to explore the association of plasma miRNA dynamics with response to neoadjuvant chemotherapy (NCT) and disclose early markers for predicting sensitivity. Methods: One hundred and nine patients with operable or locally advanced breast cancer, who participated in a prospective clinical trial and received NCT, were analyzed. Blood samples were collected before random assignment, after two cycles of chemotherapy (C2) and before surgery. Based on their clinical response, the patients were defined as chemo-sensitive or insensitive. First, baseline and preoperative samples of selected cases from both groups were screened via TaqMan miRNA array for candidate miRNAs. Afterward all the biospecimens were tested for the candidate miRNAs (miR-222, miR-20a, miR-451, miR-9, miR-34a, miR-155, and miR-145) by quantitative real-time PCR. Finally, logistic regression model was utilized to determine the predictive value of baseline/C2 expression of these miRNAs. Results: Based on the results of microRNA profiling, seven miRNAs were selected for further validation. In the HR+/HER2- cohort (n = 51) dynamics of three miRNAs, including miR-222, miR-20a, and miR-451, were associated with chemo-sensitivity. Importantly, across all the three subtypes we consistently identified chemo-induced decrease in plasma miR-34a in the insensitive patients. Finally, baseline miR-222 overexpression (OR = 6.422, P = 0.049), C2 miR-20a up-regulation (OR = 0.144, P = 0.021) and C2 miR-451 down-regulation (OR = 8.213, P = 0.012) were predictive markers of response to NCT in HR+/HER2- breast cancer. Conclusions: We described that dynamics of circulating miRNAs might help predict clinical response to NCT in breast cancer.