Title: CYP2D6 Genotype and Adjuvant Tamoxifen: Meta-Analysis of Heterogeneous Study Populations
Authors: 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, M-T M
Ambrosone, C B
Beckmann, M W
Choi, J-Y
Dieudonné, A-S
Fasching, P A
Ferraldeschi, R
Gong, L
Haschke-Becher, E
Howell, A
Jordan, L B
Hamann, U
Kiyotani, K
Krippl, P
Lambrechts, Diether
Latif, A
Langsenlehner, U
Lorizio, W
Neven, Patrick
Nguyen, A T
Park, B-W
Purdie, C A
Quinlan, P
Renner, W
Schmidt, M
Schwab, M
Shin, J-G
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 #
Issue Date: Feb-2014
Publisher: Mosby
Series Title: Clinical Pharmacology and Therapeutics vol:95 issue:2 pages:216-227
Article number: 10.1038/clpt.2013.186
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.Clinical Pharmacology & Therapeutics (2013); advance online publication 18 December 2013. doi:10.1038/clpt.2013.186.
ISSN: 0009-9236
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Translational Genetics (Vesalius Research Center) (+)
× corresponding author
# (joint) last author

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