CYP2D6 Genotype and Adjuvant Tamoxifen: Meta-Analysis of Heterogeneous Study Populations

نویسندگان

  • M A Province
  • M P Goetz
  • H Brauch
  • D A Flockhart
  • J M Hebert
  • R Whaley
  • V J Suman
  • W Schroth
  • S Winter
  • H Zembutsu
  • T Mushiroda
  • W G Newman
  • M-T M Lee
  • C B Ambrosone
  • M W Beckmann
  • J-Y Choi
  • A-S Dieudonné
  • P A Fasching
  • R Ferraldeschi
  • L Gong
  • E Haschke-Becher
  • A Howell
  • L B Jordan
  • U Hamann
  • K Kiyotani
  • P Krippl
  • D Lambrechts
  • A Latif
  • U Langsenlehner
  • W Lorizio
  • P Neven
  • A T Nguyen
  • B-W Park
  • C A Purdie
  • P Quinlan
  • W Renner
  • M Schmidt
  • M Schwab
  • J-G Shin
  • J C Stingl
  • P Wegman
  • S Wingren
  • A H B Wu
  • E Ziv
  • G Zirpoli
  • A M Thompson
  • V C Jordan
  • Y Nakamura
  • R B Altman
  • M M Ames
  • R M Weinshilboum
  • M Eichelbaum
  • J N Ingle
  • T E Klein
چکیده

The International Tamoxifen Pharmacogenomics Consortium was established to address the controversy regarding cytochrome P450 2D6 (CYP2D6) status and clinical outcomes in tamoxifen therapy. We performed a meta-analysis on data from 4,973 tamoxifen-treated patients (12 globally distributed sites). Using strict eligibility requirements (postmenopausal women with estrogen receptor-positive breast cancer, receiving 20 mg/day tamoxifen for 5 years, criterion 1); CYP2D6 poor metabolizer status was associated with poorer invasive disease-free survival (IDFS: hazard ratio = 1.25; 95% confidence interval = 1.06, 1.47; P = 0.009). However, CYP2D6 status was not statistically significant when tamoxifen duration, menopausal status, and annual follow-up were not specified (criterion 2, n = 2,443; P = 0.25) or when no exclusions were applied (criterion 3, n = 4,935; P = 0.38). Although CYP2D6 is a strong predictor of IDFS using strict inclusion criteria, because the results are not robust to inclusion criteria (these were not defined a priori), prospective studies are necessary to fully establish the value of CYP2D6 genotyping in tamoxifen therapy.

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عنوان ژورنال:

دوره 95  شماره 

صفحات  -

تاریخ انتشار 2014