Correlation of UGT2B7 Polymorphism with Cardiotoxicity in Breast Cancer Patients Undergoing Epirubicin/Cyclophosphamide-Docetaxel Adjuvant Chemotherapy

ABSTRACT

PURPOSE: The present study aimed to investigate correlations between uridine glucuronosyltransferase 2B7 (UGT2B7) -161 single nucleotide polymorphism C to T (C>T) and the occurrence of cardiotoxicity in Chinese breast cancer (BC) patients undergoing epirubicin/cyclophosphamide-docetaxel (EC-D) adjuvant chemotherapy. MATERIALS AND METHODS: 427 BC patients who had underwent surgery were consecutively enrolled in this prospective cohort study. All patients were scheduled to receive EC-D adjuvant chemotherapy regimen, and they were divided into UGT2B7 -161 CC (n=141), UGT2B7 -161 CT (n=196), and UGT2B7 -161 TT (n=90) groups according to their genotypes. Polymerase chain reaction was performed for determination of UGT2B7 -161 genotypes. Cardiotoxicity was defined as an absolute decline in left ventricular ejection fraction (LVEF) of at least 10% points from baseline to a value less than 53%, heart failure, acute coronary artery syndrome, or fatal arrhythmia. RESULTS: LVEF values were lower at cycle (C) 4, C8, 3 months after chemotherapy (M3), M6, M9, and M12 compared to C0 (all p < 0.001), in BC patients undergoing EC-D adjuvant chemotherapy. Cardiotoxicity was recorded for 4.2% of the overall population and was lowest in the UGT2B7 -161 TT group (1.1%), compared to UGT2B7 -161 CT (3.1%) and UGT2B7 -161 CC (7.8%) group (p=0.026). Multivariate logistic regression revealed that UGT2B7 -161 T allele could independently predict a low occurrence of cardiotoxicity in BC patients undergoing EC-D adjuvant chemotherapy (p=0.004). CONCLUSION: A UGT2B7 -161 T allele serves as a potential biomarker for predicting a low occurrence of cardiotoxicity in BC patients undergoing EC-D adjuvant chemotherapy.