Impact of UGT2B7 His268Tyr polymorphism on the outcome of adjuvant epirubicin treatment in breast cancer

This is a pharmacogenetic study based on samples collected from 745 breast cancer patients of the Austrian Tumor of breast tissue: Incidence, Genetics, and Environmental Risk factors (TIGER) cohort who did not present metastases at baseline. This cohort included 205 women with epirubicin-based combination chemotherapy, 113 patients having received chemotherapy without epirubicin and 427 patients having received no chemotherapy at all. Of the epirubicin-treated subgroup, 120 were subsequently treated with tamoxifen. For all women UGT2B7His268Tyr was genotyped. Invasive disease-free survival was assessed using Kaplan-Meier and Cox's proportional hazard regression analysis.Among the 205 epirubicin-treated patients, carriers of two UGT2B7268Tyr alleles had a mean invasive disease-free survival of 8.6 (95% confidence interval (CI) 7.9 to 9.3) years as compared to 7.5 (95% CI 6.9 to 8.0) years in carriers of at least one UGT2B7268His allele (adjusted hazard ratio (HR) = 2.64 (95% CI 1.22 to 5.71); P = 0.014). In addition, the impact of the UGT2B7His268Tyr polymorphism became even more pronounced in patients subsequently treated with tamoxifen (adjusted HR = 5.22 (95% CI 1.67 to 26.04); P = 0.015) whereas no such difference in invasive disease-free survival was observed in patients not receiving epirubicin.Breast cancer patients carrying the UGT2B7268Tyr/Tyr genotype may benefit most from adjuvant epirubicin-based chemotherapy. These results warrant confirmation in further studies.Anthracyclines are commonly used for neoadjuvant or adjuvant chemotherapy of locally advanced breast cancer [1,2]. They act by inhibition of topoisomerase II alpha and generation of reactive oxygen species eventually resulting in cell cycle arrest and apoptosis [3,4]. Epirubicin is a semisynthetic derivative of doxorubicin preferentially used in breast cancer treatment. It is extensively metabolized in the liver to epirubicinol by aldo-keto reductase and in addition aglycones of epirubicin and ep