Circulating MicroRNAs As Indicators in the Prediction of Neoadjuvant Chemotherapy Response in Luminal B Breast Cancer

Purpose: Circulating microRNAs (miRNAs) have been indicated as predictive biomarker for the response to neoadjuvant chemotherapy (NAC) and the prognosis of breast cancer (BC); however, to date the conclusions have been controversial. The biological characteristics of BC were affected by molecular subtypes. Hence, we aimed to investigate the predictive effect of miRNAs on NAC response in luminal B BC patients.

Methods: Thirty-seven luminal B BC patient under NAC were prospectively enrolled in this study. Based on their clinical, pathological, and comprehensive response, the patients were defined as responder or non-responders, respectively. Circulating miRNAs were isolated from blood samples before and at the middle of NAC, and candidate miRNAs (miR-34a-5p, miR-125b-5p, miR-210, miR-222, miR-375, miR-718, miR-4516, and let-7g) were analyzed by quantitative real-time polymerase chain reaction (PCR). In addition, the association between miRNAs and disease-free survival (DFS) was examined.

Results: miR-718, miR-4516, miR-210, and miR-125b-5p were found to be specific miRNAs associated with chemo-sensitivity of luminal B HER2 negative patients (n = 24). In the luminal B HER2 positive cohort (n = 13), dynamics of miR-222 and let-7g correlated with pathological response. Treatment-induced increase in miR-34a-5p in the responders except who reached pathologic complete response (pCR) was consistently identified across all luminal B patients and its two subgroups. Finally, after adjustments for Neo-Bioscore, patients with increased levels of miR-125b-5p during NAC had a worse DFS than those with decreased levels (HR = 5.86, 95% CI = 1.39-24.62, p = 0.016).

Conclusion: Specific circulating miRNAs were identified as predictive markers for NAC response and prognosis in luminal B BC. The underlying mechanism needs further studies.