Longitude Variation of the microRNA-497/FGF-23 Axis during Treatment and Its Linkage with Neoadjuvant/Adjuvant Trastuzumab-Induced Cardiotoxicity in HER2-Positive Breast Cancer Patients

PURPOSE: MicroRNA-497 (miR-497) is previously reported to target fibroblast growth factor 23 (FGF-23) and regulates cardiac injury, while their value in predicting drug-induced cardiotoxicity is not reported. Thus, the current study aimed to investigate the correlation of miR-497/FGF-23 with neoadjuvant/adjuvant trastuzumab-induced cardiotoxicity in human epidermal growth factor receptor 2 (HER2)-positive breast cancer patients. METHODS: A total of 97 HER2-positive surgical breast cancer patients who received neoadjuvant/adjuvant trastuzumab contained regimens were enrolled; then, their peripheral blood mononuclear cells (PBMC) and serum were collected at baseline, after neoadjuvant treatment, at 3 months (M3), 6 months (M6), 9 months (M9), and 12 months (M12) after surgery. The PBMC was used for miR-497 measurements, and the serum was used for FGF-23 measurements. The cardiotoxicity events and incidence were recorded. RESULTS: A total of 24 (24.7%) patients occurred cardiotoxicity during the treatment period. MiR-497 decreased from baseline (median: 0.955) to M12 after surgery (median: 0.602) (p < 0.001), while FGF-23 increased from baseline (median: 0.390 ng/mL) to M12 after surgery (median: 0.566 ng/mL) (p < 0.001); besides, the miR-497/FGF-23 axis greatly reduced from baseline (median: 2.545) to M12 after surgery (median: 1.222) (p < 0.001). At most time points, miR-497 was negatively related to FGF-23 (all p < 0.05). Notably, the miR-497/FGF-23 axis at all time points (including baseline, postneoadjuvant treatment, M3, M6, M9, and M12) was related to a lower risk of cardiotoxicity (all p < 0.05). Furthermore, the miR-497/FGF-23 axis was also positively correlated with the left ventricular ejection fraction (LVEF) at all time points (all p < 0.01). CONCLUSION: The MiR-497/FGF-23 axis serves as a potential indicator predicting trastuzumab-induced cardiotoxicity in HER2-positive breast cancer patients.