@article{de59b3a1b1ae4e21bb72e2678680ea25,
title = "CYP2D6 genotype and adjuvant tamoxifen: meta-analysis of heterogeneous study populations",
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.",
author = "Province, {M. A.} and Goetz, {M. P.} and H. Brauch and Flockhart, {D. A.} and Hebert, {J. M.} and R. Whaley and Suman, {V. J.} and W. Schroth and S. Winter and H. Zembutsu and T. Mushiroda and Newman, {W. G.} and Lee, {M-T M.} and Ambrosone, {C. B.} and Beckmann, {M. W.} and J-Y Choi and A-S Dieudonn{\'e} and Fasching, {P. A.} and R. Ferraldeschi and L. Gong and E. Haschke-Becher and A Howell and Jordan, {L. B.} and U. Hamann and K. Kiyotani and P. Krippl and D. Lambrechts and A Latif and U. Langsenlehner and W. Lorizio and P. Neven and Nguyen, {A. T.} and B-W Park and Purdie, {C. A.} and P. Quinlan and W. Renner and M. Schmidt and M. Schwab and J-G Shin and Stingl, {J. C.} and P. Wegman and S. Wingren and Wu, {A. H. B.} and E. Ziv and G. Zirpoli and Thompson, {A. M.} and Jordan, {V. C.} and Y. Nakamura and Altman, {R. B.} and Ames, {M. M.} and Weinshilboum, {R. M.} and M. Eichelbaum and Ingle, {J. N.} and Klein, {T. E.}",
note = "This work was supported by grants from the National Institutes of Health (National Institute of General Medical Sciences, the National Cancer Institute, and the National Institute of Child Health and Human Development R24 GM61374, CA-25224, CA-37404, CA-15083, CA-35113, CA-35269, CA-63849, CA35103, CA-35195, CA-35272, CA-35101, CA-37417, CA-35415, CA-52352, CA-35448, CA-60274, 1R01CA133049-01, U19 GM61388, CA-116201, CA-58207, CA-51008, T32 GM007546, and CA051008; Breast Cancer Research (Scotland); Tayside Tissue Bank; California Breast Cancer Research Program grant 14OB-0166; Cancer Research UK; Deutsches Krebsforschungszentrum, Heidelberg, Germany; Robert Bosch Foundation, Stuttgart, Germany; 7FP EU Marie Curie Initial Training Network “FightingDrugFailure” (GA 238132); GrantStichting Emmanuel van der Schueren (scientific partner of the Vlaamse Liga tegen Kanker); and the National Project for Personalized Genomic Medicine, Ministry for Health & Welfare, Republic of Korea (A111218-PG02). W.S. is supported by grant Deutsche Forschungsgemeinschaft SCHR 1323/2-1, Germany.",
year = "2014",
month = feb,
doi = "10.1038/clpt.2013.186",
language = "English",
volume = "95",
pages = "216--227",
journal = "Clinical Pharmacology & Therapeutics",
issn = "0009-9236",
publisher = "Wiley",
number = "2",
}
