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CYP2D6 genotype and adjuvant tamoxifen: meta-analysis of heterogeneous study populations

Authors
 MA Province  ;  MP Goetz  ;  H Brauch  ;  DA Flockhart  ;  JM Hebert  ;  R Whaley  ;  VJ Suman  ;  W Schroth  ;  S Winter  ;  H Zembutsu  ;  T Mushiroda  ;  WG Newman  ;  M-TM Lee  ;  CB Ambrosone  ;  MW Beckmann  ;  J-Y Choi  ;  A-S Dieudonné  ;  PA Fasching  ;  R Ferraldeschi  ;  L Gong  ;  E Haschke-Becher  ;  A Howell  ;  LB Jordan  ;  U Hamann  ;  K Kiyotani  ;  P Krippl  ;  D Lambrechts  ;  A Latif  ;  U Langsenlehner  ;  W Lorizio  ;  P Neven  ;  AT Nguyen  ;  B-W Park  ;  CA Purdie  ;  P Quinlan  ;  W Renner  ;  M Schmidt  ;  M Schwab  ;  J-G Shin  ;  JC Stingl  ;  P Wegman  ;  S Wingren  ;  AHB Wu  ;  E Ziv  ;  G Zirpoli  ;  AM Thompson  ;  VC Jordan  ;  Y Nakamura  ;  RB Altman  ;  MM Ames  ;  RM Weinshilboum  ;  M Eichelbaum  ;  JN Ingle  ;  TE Klein  ;  on behalf of the International Tamoxifen Pharmacogenomics Consortium 
Citation
 Clinical Pharmacology & Therapeutics, Vol.95(2) : 216-227, 2014 
Journal Title
 Clinical Pharmacology & Therapeutics 
ISSN
 0009-9236 
Issue Date
2014
Abstract
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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DOI
10.1038/clpt.2013.186
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
Yonsei Authors
박병우(Park, Byeong Woo) ORCID logo https://orcid.org/0000-0003-1353-2607
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URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/166049
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