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


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.

SUBMITTER: Province MA 

PROVIDER: S-EPMC3904554 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature

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

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

Clinical pharmacology and therapeutics 20130923 2


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 asso  ...[more]

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