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CYP2D6 Genotype and Adjuvant Tamoxifen: Meta‐Analysis of Heterogeneous Study Populations
Author(s) -
Province M A,
Goetz M P,
Brauch H,
Flockhart D A,
Hebert J M,
Whaley R,
Suman V J,
Schroth W,
Winter S,
Zembutsu H,
Mushiroda T,
Newman W G,
Lee MT M,
Ambrosone C B,
Beckmann M W,
Choi JY,
Dieudonné AS,
Fasching P A,
Ferraldeschi R,
Gong L,
HaschkeBecher E,
Howell A,
Jordan L B,
Hamann U,
Kiyotani K,
Krippl P,
Lambrechts D,
Latif A,
Langsenlehner U,
Lorizio W,
Neven P,
Nguyen A T,
Park BW,
Purdie C A,
Quinlan P,
Renner W,
Schmidt M,
Schwab M,
Shin JG,
Stingl J C,
Wegman P,
Wingren S,
Wu A H B,
Ziv E,
Zirpoli G,
Thompson A M,
Jordan V C,
Nakamura Y,
Altman R B,
Ames M M,
Weinshilboum R M,
Eichelbaum M,
Ingle J N,
Klein T E
Publication year - 2014
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.2013.186
Subject(s) - tamoxifen , hazard ratio , medicine , oncology , breast cancer , pharmacogenomics , cyp2d6 , confidence interval , cancer , pharmacology , cytochrome p450 , metabolism
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. Clinical Pharmacology & Therapeutics (2014); 95 2, 216–227. doi: 10.1038/clpt.2013.186