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

Province, M
; 
Goetz, M
; 
Brauch, H
; 
Flockhart, D
; 
Hebert, J
; 
Whaley, R
; 
Suman, V
; 
Schroth, W
; 
Winter, S
; 
Zembutsu, H
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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.
Authors
Province, M
Goetz, M
Brauch, H
Flockhart, D
Hebert, J
Whaley, R
Suman, V
Schroth, W
Winter, S
Zembutsu, H
Mushiroda, T
Newman, W
Lee, M
Ambrosone, C
Beckmann, M
Choi, J
Dieudonné, A
Fasching, P
Ferraldeschi, R
Gong, L
Haschke-Becher, E
Howell, Anthony
Jordan, L
Hamann, U
Kiyotani, K
Krippl, P
Lambrechts, D
Latif, A
Langsenlehner, U
Lorizio, W
Neven, P
Nguyen, A
Park, B
Purdie, C
Quinlan, P
Renner, W
Schmidt, M
Schwab, M
Shin, J
Stingl, J
Wegman, P
Wingren, S
Wu, A
Ziv, E
Zirpoli, G
Thompson, A
Jordan, V
Nakamura, Y
Altman, R
Ames, M
Weinshilboum, R
Eichelbaum, M
Ingle, J
Klein, T
Affiliation
Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, Missouri, USA.
Description
Date
2014-02
Publisher
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All Christie Publications
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Type
Article
Citation
CYP2D6 genotype and adjuvant tamoxifen: meta-analysis of heterogeneous study populations. 2014, 95 (2):216-27 Clin Pharmacol Ther
Journal Title
Journal ISSN
Volume Title
URI
http://hdl.handle.net/10541/314896
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