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CYP2D6 Genotype and Adjuvant Tamoxifen: Meta-Analysis of Heterogeneous Study Populations
Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis MO, USA.
Department of Oncology and Pharmacology, Mayo Clinic, Rochester MN, USA.
Dr Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany; Tübingen University, Tübingen, Germany.
Division of Clinical Pharmacology, School of Medicine, Indiana University, Bloomington IN, USA.
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2014 (English)In: Clinical Pharmacology and Therapeutics, ISSN 0009-9236, E-ISSN 1532-6535, Vol. 95, no 2, p. 216-227Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
New York, USA: Nature Publishing Group, 2014. Vol. 95, no 2, p. 216-227
National Category
Medical and Health Sciences Pharmacology and Toxicology
Research subject
Medicine
Identifiers
URN: urn:nbn:se:oru:diva-33895DOI: 10.1038/clpt.2013.186ISI: 000330151100026PubMedID: 24060820Scopus ID: 2-s2.0-84893732936OAI: oai:DiVA.org:oru-33895DiVA, id: diva2:698647
Note

Funding Agencies:

National Institutes of Health (National Institute of General Medical Sciences)

National Institutes of Health (National Cancer Institute)

National Institutes of Health (National Institute of Child Health and Human Development)

Breast Cancer Research (Scotland)  

Tayside Tissue Bank  

California Breast Cancer Research Program 

Cancer Research UK  

Deutsches Krebsforschungszentrum, Heidelberg, Germany  

Robert Bosch Foundation, Stuttgart, Germany  

Marie Curie Initial Training Network "FightingDrugFailure" 

GrantStichting Emmanuel van der Schueren (scientific partner of the Vlaamse Liga tegen Kanker)  

National Project for Personalized Genomic Medicine, Ministry for Health & Welfare, Republic of Korea 

Deutsche Forschungsgemeinschaft, Germany 

Available from: 2014-02-24 Created: 2014-02-24 Last updated: 2018-08-27Bibliographically approved

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Wegman, PiaWingren, Sten

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