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RESEARCH PRODUCT
CYP2D6 genotype and adjuvant tamoxifen: meta-analysis of heterogeneous study populations.
P KripplM-t M LeeAlan H.b. WuE Haschke-becherVera J. SumanYusuke NakamuraR FerraldeschiTeri E. KleinU HamannWerner SchrothM SchmidtM SchmidtChristine B. AmbrosoneJulia C. StinglWendy LorizioRichard M. WeinshilboumGary ZirpoliMichel EichelbaumJn IngleMichael A. ProvinceP WegmanLi GongAnthony HowellMatthias W. BeckmannVirgil Craig JordanAm ThompsonHitoshi ZembutsuA-s DieudonnéRuss B. AltmanAyse LatifStefan WinterS WingrenJ-y ChoiT MushirodaJ-g ShinMatthias SchwabMatthew M. AmesRyan WhaleyDavid A. FlockhartAnne T. NguyenLee B. JordanPatrick NevenWilliam G. NewmanU LangsenlehnerElad ZivColin A. PurdieMatthew P. GoetzJoan M. HebertPhilip R. QuinlanPeter A. FaschingPeter A. FaschingHiltrud BrauchW RennerDiether LambrechtsB-w ParkKazuma Kiyotanisubject
Oncologymedicine.medical_specialtyAntineoplastic Agents HormonalGenotypeBreast Neoplasms030226 pharmacology & pharmacy03 medical and health sciences0302 clinical medicineBreast cancerInternal medicinemedicineHumansPharmacology (medical)skin and connective tissue diseasesProspective cohort studySurvival analysisAgedPharmacologyGynecologybusiness.industryHazard ratioGenetic VariationMiddle Agedmedicine.diseaseSurvival AnalysisConfidence interval3. Good healthTamoxifenTreatment OutcomeCytochrome P-450 CYP2D6Pharmacogenetics030220 oncology & carcinogenesisMeta-analysisFemaleMenopausebusinessTamoxifenPharmacogeneticsmedicine.drugdescription
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2013-06-03 | Clinical pharmacology and therapeutics |