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- Title
CYP2D6 Genotype and Adjuvant Tamoxifen: Meta-Analysis of Heterogeneous Study Populations.
- 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
- 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.
- Subjects
TAMOXIFEN; META-analysis; CYTOCHROME P-450; PHARMACOGENOMICS; ESTROGEN receptors; BREAST cancer treatment
- Publication
Clinical Pharmacology & Therapeutics, 2014, Vol 95, Issue 2, p216
- ISSN
0009-9236
- Publication type
Article
- DOI
10.1038/clpt.2013.186