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

Province MA, Goetz MP, Brauch H, Flockhare DA, Hebert JM, Whaley R, Suman VJ, Schroth W, Winter S, Zembutsu H, Mushiroda T, Newman WG, Lee MTM, Ambrosone CB, Beckmann M, Choi JY, Dieudonne AS, Fasching P, Ferraldeschi R, Gong L, Haschke-Becher E, Howel A, Jordan LB, Hamann U, Kiyotani K, Krippl P, Lambrechts D, Latif A, Langsenlehner U, Lorizio W, Neven P, Nguyen AT, Park BW, Purdie CA, Quinlan P, Renner W, Schmidt M, Schwab M, Shin JG, Stingl JC, Wegman P, Wingren S, Wu AHB, Ziv E, Zirpoli G, Thompson AM, Jordan VC, Nakamura Y, Altman RB, Ames MM, Weinshilboum RM, Eichelbaum M, Ingle JN, Klein TE (2014)


Publication Type: Journal article

Publication year: 2014

Journal

Book Volume: 95

Pages Range: 216-27

Journal Issue: 2

DOI: 10.1038/clpt.2013.186

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.

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APA:

Province, M.A., Goetz, M.P., Brauch, H., Flockhare, D.A., Hebert, J.M., Whaley, R.,... Klein, T.E. (2014). CYP2D6 genotype and adjuvant tamoxifen: meta-analysis of heterogeneous study populations. Clinical Pharmacology & Therapeutics, 95(2), 216-27. https://dx.doi.org/10.1038/clpt.2013.186

MLA:

Province, M. A., et al. "CYP2D6 genotype and adjuvant tamoxifen: meta-analysis of heterogeneous study populations." Clinical Pharmacology & Therapeutics 95.2 (2014): 216-27.

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