CYP2D6 genotype and adjuvant tamoxifen: meta-analysis of heterogeneous study populations.
作者： Michael A Province , Matthew P Goetz , Hiltrud Brauch , David A Flockhart , Joan M Hebert
关键词: Tamoxifen 、 Pharmacogenomics 、 Internal medicine 、 Gynecology 、 Pharmacogenetics 、 Breast cancer 、 Confidence interval 、 Meta-analysis 、 Survival analysis 、 Hazard ratio 、 Oncology 、 Medicine
摘要: 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 for 5 years, criterion 1); CYP2D6 poor metabolizer associated poorer invasive disease–free survival (IDFS: hazard ratio = 1.25; 95% confidence interval 1.06, 1.47; P 0.009). However, not statistically significant when duration, menopausal status, annual follow-up were specified (criterion 2, n 2,443; 0.25) or no exclusions applied 3, 4,935; 0.38). Although is strong predictor of IDFS using inclusion criteria, because results are robust criteria (these defined priori), prospective studies necessary fully establish value genotyping therapy. Clinical Pharmacology & Therapeutics (2014); 95 216–227. doi:10.1038/clpt.2013.186
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