Year: 2013
Type: review
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: M A Province, M P Goetz, H Brauch, D A Flockhart, J M Hebert, R Whaley, V J Suman, W Schroth, S Winter, H Zembutsu, T Mushiroda, W G Newman, M-T M Lee, C B Ambrosone, M W Beckmann, J-Y Choi, A-S Dieudonné, P A Fasching, R Ferraldeschi, L Gong, E Haschke-Becher, A Howell, L B Jordan, U Hamann, K Kiyotani, P Krippl, D Lambrechts, A Latif, U Langsenlehner, W Lorizio, P Neven, A T Nguyen, B-W Park, C A Purdie, P Quinlan, W Renner, M Schmidt, M Schwab, J-G Shin, J C Stingl, P Wegman, S Wingren, A H B Wu, E Ziv, G Zirpoli, A M Thompson, V C Jordan, Y Nakamura, R B Altman, M M Ames, R M Weinshilboum, M Eichelbaum, J N Ingle, T E Klein
Institutions: Washington University in St. Louis, Mayo Clinic, Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, University of Tübingen, Indiana University Bloomington, Indiana University, Stanford University, The University of Tokyo, RIKEN, Manchester Academic Health Science Centre, University of Manchester, RIKEN Center for Integrative Medical Sciences, Roswell Park Comprehensive Cancer Center, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsklinikum Erlangen, Seoul National University, KU Leuven, University of California, Los Angeles, Paracelsus Medical University, The Christie NHS Foundation Trust, Ninewells Hospital, German Cancer Research Center, Medical University of Graz, University of California, San Francisco, UCSF Helen Diller Family Comprehensive Cancer Center, Universitair Ziekenhuis Leuven, Yonsei University, Yonsei University Health System, Johannes Gutenberg University Mainz, Universitätsklinikum Tübingen, Inje University, Inje University Busan Paik Hospital, Federal Institute for Drugs and Medical Devices, University of Bonn, Örebro University, Georgetown University, Stanford Medicine
Language: English
Subfield: Pharmacology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $4,410
Funders: Washington University in St. Louis, Deutsches Krebsforschungszentrum, University of Dundee, Bundesinstitut für Arzneimittel und Medizinprodukte, Cancer Research UK, European Commission, Robert Bosch Stiftung, Deutsche Forschungsgemeinschaft, Yonsei University, Inje University, Örebro Universitet, Vlaamse Liga Tegen Kanker, Rheinische Friedrich-Wilhelms-Universität Bonn, University of California, San Francisco, Japan Society for the Promotion of Science, RIKEN, Busan Paik Hospital, Inje University, National Cancer Institute, National Institute of General Medical Sciences
Awards: G1094409381, G1109514914, G1111985063, G1119724336, G1209692471, G1423238671, G1539327064, G1672400004, G1695119531, G179864828, G1828094709, Illinois Oncology Research Association Community Clinical Oncology Program, G2082142344, Priorities and Standards in Pharmacogenomic Research: Opportunities for a Safer and More Efficient Pharmacotherapy, G2268849960, G2366400345, G2383270398, G2440672419, G248987615, G2514509764, G3167125069, PharmGKB: pharmacogenomics knowledge for precision medicine, G3328427954, G358241105, G3789417232, G4088506818, Ochsner Community Clinical Oncology Program, G4257885129, G42877212, G431899019, G454726209, G456380056, G4629521321, Identification and functional analysis of the gene(s) associated with endcrine therapy for breast cancer., G5916996170, North Central Cancer Treatment Group, Cedar Rapids Oncology Project, Missouri Valley Cancer Consortium CCOP, Duluth Community Clinical Oncology Program, G7696172874, G8386859579, G844520391, Iowa Oncology Research Association, G8652730736, G88962385, Georgetown University Lombardi Comprehensive Cancer Center Support Grant, Mayo Clinic Comprehensive Cancer Center Support Grant, G989507227
OpenAlex ID: W2082048952