CYP2D6 Genotype and Adjuvant Tamoxifen: Meta‐Analysis of Heterogeneous Study Populations. Issue 2 (23rd September 2013)

• Record Type: Journal Article
• 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, D; Latif, A; Langsenlehner, U; Lorizio, W; Neven, P; 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; International Tamoxifen Pharmacogenomics Consortium;
• Is Part Of: Clinical pharmacology & therapeutics. Volume 95:Issue 2(2014)
• Page Start: 216
• Page End: 227
• Publication Date: 2013-09-23
• Subjects: Pharmacology -- Periodicals; Therapeutics -- Periodicals; 615.5
• DOI: 10.1038/clpt.2013.186
• Languages: English
• ISSNs: 0009-9236

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>The International Tamoxifen Pharmacogenomics Consortium was established to address the controversy regarding cytochrome P450 2D6 (<italic>CYP2D6</italic>) 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; <italic>P</italic> = 0.009). However, <italic>CYP2D6</italic> status was not statistically significant when tamoxifen duration, menopausal status, and annual follow‐up were not specified (criterion 2, <italic>n</italic> = 2, 443; <italic>P</italic> = 0.25) or when no exclusions were applied (criterion 3, <italic>n</italic> = 4, 935; <italic>P</italic> = 0.38). Although <italic>CYP2D6</italic> is a strong predictor of IDFS using strict inclusion criteria, because the results are not robust to inclusion criteria (these were not defined <italic>a priori</italic>), prospective studies are necessary to fully establish the value of <italic>CYP2D6</italic> genotyping in tamoxifen therapy.</p> <p> <italic>Clinical Pharmacology & Therapeutics</italic> (2014); <bold>95</bold> 2, 216–227. doi:<ext-link ext-link-type="doi" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink">10.1038/clpt.2013.186</ext-link></p> </abstract>