A Uridine Glucuronosyltransferase 2B7 Polymorphism Predicts Epirubicin Clearance and Outcomes in Early-Stage Breast Cancer

Background Epirubicin is metabolized by uridine glucuronosyltransferase 2B7 (UGT2B7), an enzyme rich in single nucleotide polymorphisms (SNPs). We studied whether the -161 C > T germline SNP in UGT2B7 was related to epirubicin metabolism and whether differences exist in the toxicity and efficacy of epirubicin-based chemotherapy among patients who were TT homozygotes, CT heterozygotes, and CC homozygotes. Patients and Methods A total of 132 women with non-metastatic breast cancer receiving FEC (5-fluorouracil 500 mg/m², epirubicin 100 mg/m², cyclophosphamide 500 mg/m²) were prospectively enrolled. Toxicity was assessed in cycle 1 using the National Cancer Institute Common Toxicity Criteria, version 2.0. Results The sequence at -161 was studied in 132 subjects; 37 were TT homozygotes, 63 were CT heterozygotes, 26 were CC homozygotes, and 6 could not be genotyped. The CC genotype patients had decreased epirubicin clearance (median, 103.3 L/hr) compared with the CT/TT genotype patients (median, 134.0 L/hr; P =.002). The CC homozygous patients had an increased risk of grade 3 to 4 leukopenia compared with the TT homozygotes or heterozygotes (P =.038 and P =.032, respectively). TT homozygotes or heterozygotes had an increased risk of early recurrence (P =.039; χ² test). Conclusion The results of the present prospective pharmacogenetic study suggest that the UGT2B7 -161 C > T SNP correlate with drug metabolism, toxicity, and efficacy in patients receiving epirubicin chemotherapy. Further studies of this UGT2B7 SNP as a predictor of epirubicin toxicity and efficacy are warranted.