Serum miR-222-3p as a Double-Edged Sword in Predicting Efficacy and Trastuzumab-Induced Cardiotoxicity for HER2-Positive Breast Cancer Patients Receiving Neoadjuvant Target Therapy

Abstract

<b>Background:</b> We aimed to explore whether the expression of serum miR-222-3p might contribute to early prediction of therapeutic response, clinical outcomes, and adverse events for HER2-positive breast cancer patients receiving neoadjuvant therapy (NAT). <b>Methods:</b> A total of 65 HER2-positive breast cancer patients receiving NAT were analyzed. The concentration of serum miR-222-3p was detected by quantitative real-time PCR. Logistic regression analysis was used to identify the association of serum miR-222-3p with pathological complete response (pCR). The relationship of serum miR-222-3p with disease-free survival (DFS) and overall survival (OS) was examined via log-rank test and Cox proportional hazards analysis. The ordered logistic regression was applied to evaluate the association between serum miR-222-3p and adverse events. <b>Results:</b> The miR-222-3p low group was more likely to achieve pCR [odds ratio (OR) = 0.258, <i>P</i> = 0.043]. The interaction between miR-222-3p and presenting Ki67 level was also detected for pCR (OR = 49.230, <i>P</i> _{<i>interaction</i>} = 0.025). The miR-222-3p low group was correlated with superior DFS (<i>P</i> = 0.029) and OS (<i>P</i> = 0.0037). The expression of serum miR-222-3p was the independent protective factor for trastuzumab-induced cardiotoxicity (<i>P</i> < 0.05) and anemia (<i>P</i> = 0.013). <b>Conclusions:</b> Serum miR-222-3p is the potential factor to predict pCR, survival benefit and trastuzumab-induced cardiotoxicity for HER2-positive breast cancer patients receiving NAT.