Qian Zhang, Dengfeng Chen
Department of Galactophore, Jingzhou Hospital, Yangtze University, Jingzhou 434000, China.
Summary
Purpose: The purpose of this study was to explore fibroblast growth factor-23 (FGF-23) expression and its predictive value on cardiotoxicity risk induced by adjuvant trastuzumab combined with chemotherapy in HER2 positive (HER2+ ) breast cancer patients.
Methods: Enrolled were 105 HER2+ breast cancer patients about to receive adjuvant epirubicin combined with cyclophosphamide followed by docetaxel and trastuzumab (EC- >D+T) treatment after surgery. Their serum FGF-23 levels pre adjuvant therapy were determined by enzyme-linked immunosorbent assay (ELISA). Cardiotoxicity was monitored at 3 months (M), M6, M9, M12, and M15 after treatment.
Results: The mean FGF-23 level was 333.7±130.3 pg/ml, and it was correlated with increased rates of hypertension (p=0.014) and chronic kidney disease (CKD) (p=0.025), decreased LVEF (r=-0.250, p=0.010), elevated cardiac troponin I (cTnl) (r=0.395, p<0.001) and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) (r=0.367, p<0.001). Regarding cardiotoxicity rate, it was 0.0%, 0.0%, 1.9%, 11.4%, 17.1% and 19.0% at M0, M3, M6, M9, M12 and M15 respectively, which was stable at M0 and M3, while was obviously increased from M3 to M15. Compared with non-cardiotoxicity patients, FGF-23 level was higher in cardiotoxicity patients (410.1±165.2 vs. 315.7±114.6 pg/ml) (p=0.003), and it (p=0.021) was an independent risk factor predicting cardiotoxicity by multivariate logistic regression analysis, also had a good predictive value for cardiotoxicity risk (AUC: 0.664; 95%CI: 0.529-0.799) by receiver operating characteristic (ROC) curves.
Conclusions: FGF-23 is upregulated and correlates with hypertension, CKD and poor cardiac function. Importantly, it is an independent risk factor predicting adjuvant EC->D+T treatment induced cardiotoxicity in HER2+ breast cancer patients.
Key words: fibroblast growth factor-23, cardiotoxicity risk, human epidermal growth factor receptor-2, breast cancer, adjuvant EC->D+T treatment
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