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Wiley, Clinical Pharmacology & Therapeutics, 2(95), p. 216-227, 2013

DOI: 10.1038/clpt.2013.186

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

Journal article published in 2013 by Michael A. Province, Matthew P. Goetz, Hiltrud Brauch, David A. Flockhart, Joan M. Hebert, Ryan Whaley, Ming-Ta Michael Lee, Vera J. Suman, Werner Schroth, Taisei Mushiroda, William G. Newman, Stefan Winter, Ming-Ta Michael Lee, Hitoshi Zembutsu, Christine B. Ambrosone and other authors.
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Abstract

The International Tamoxifen Pharmacogenomics Consortium (ITPC) was established to address the controversy over CYP2D6 status and clinical outcomes in tamoxifen therapy. We performed a meta-analysis on data from 4,973 tamoxifen treated patients (twelve globally-distributed sites). Using strict eligibility requirements (postmenopausal women with estrogen receptor (ER) 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: HR=1.25; 95% CI 1.06, 1.47; P=0.009). However, CYP2D6 was not statistically significant when tamoxifen duration, menopausal status, and annual follow-up were not specified (Criterion 2, n=2443; 49%; P=0.25) nor when no exclusions were applied (Criterion 3, n=4935; 99%; 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); accepted article preview online 23 September 2013 doi:10.1038/clpt.2013.186.