title: Impact of UGT2B7 His268Tyr polymorphism on the outcome of adjuvant epirubicin treatment in breast cancer.
abstract: BACKGROUND
  Epirubicin is a common adjuvant treatment for breast cancer. It is mainly eliminated after glucuronidation through uridine diphosphate-glucuronosyltransferase 2B7 (UGT2B7). The present study aimed to describe the impact of the UGT2B7(His268Tyr) polymorphism on invasive disease-free survival in breast cancer patients after epirubicin treatment.
  
  
  METHODS
  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 UGT2B7(His268Tyr) was genotyped. Invasive disease-free survival was assessed using Kaplan-Meier and Cox's proportional hazard regression analysis.
  
  
  RESULTS
  Among the 205 epirubicin-treated patients, carriers of two UGT2B7(268Tyr) 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 UGT2B7(268His) allele (adjusted hazard ratio (HR) = 2.64 (95% CI 1.22 to 5.71); P = 0.014). In addition, the impact of the UGT2B7(His268Tyr) 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.
  
  
  CONCLUSIONS
  Breast cancer patients carrying the UGT2B7(268Tyr/Tyr) genotype may benefit most from adjuvant epirubicin-based chemotherapy. These results warrant confirmation in further studies.
authors.affiliation: Institute of Pharmacology of Natural Products and Clinical Pharmacology, University Ulm, Germany.
authors.forename: Sumit
authors.initials: S
authors.lastname: Parmar
authors.forename: Julia Carolin
authors.initials: JC
authors.lastname: Stingl
authors.forename: Ariana
authors.initials: A
authors.lastname: Huber-Wechselberger
authors.forename: Alexander
authors.initials: A
authors.lastname: Kainz
authors.forename: Wilfried
authors.initials: W
authors.lastname: Renner
authors.forename: Uwe
authors.initials: U
authors.lastname: Langsenlehner
authors.forename: Peter
authors.initials: P
authors.lastname: Krippl
authors.forename: Jürgen
authors.initials: J
authors.lastname: Brockmöller
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Haschke-Becher
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D015331:Cohort Studies; D018572:Disease-Free Survival; D015251:Epirubicin / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D005838:Genotype; D014453:Glucuronosyltransferase / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D013629:Tamoxifen / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D013629:Tamoxifen; D015251:Epirubicin; C491474:UGT2B7 protein, human; D014453:Glucuronosyltransferase