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- PMID: 24060820
- UKPMCID: 24060820
- DOI: 10.1038/clpt.2013.186
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CYP2D6 Genotype and Adjuvant Tamoxifen: Meta-analysis of Heterogeneous Study Populations.
Province, Michael A; Goetz, Matthew P; Brauch, Hiltrud; Flockhart, David A; Hebert, Joan M; Whaley, Ryan; Suman, Vera J; Schroth, Werner; Winter, Stefan; Zembutsu, Hitoshi; Mushiroda, Taisei; Newman, William G; Michael Lee, Ming-Ta; Ambrosone, Christine B; Beckmann, Matthias W; Choi, Ji-Yeob; Dieudonné, Anne-Sophie; Fasching, Peter A; Ferraldeschi, Roberta; Gong, Li; Haschke-Becher, Elisabeth; Howell, Anthony; Jordan, Lee B; Hamann, Ute; Kiyotani, Kazuma; Krippl, Peter; Lambrechts, Diether; Latif, Ayse; Langsenlehner, Uwe; Lorizio, Wendy; Neven, Patrick; Nguyen, Anne T; Park, Byeong-Woo; Purdie, Colin A; Quinlan, Philip; Renner, Wilifried; Schmidt, Marcus; Schwab, Matthias; Shin, Jae-Gook; Stingl, Julia C; Wegman, Pia; Wingren, Sten; Wu, Alan H B; Ziv, Elad; Zirpoli, Gary; Thompson, Alastair M; Jordan, V Craig; Nakamura, Yusuke; Altman, Russ B; Ames, Matthew M; Weinshilboum, Richard M; Eichelbaum, Michel; Ingle, James N; Klein, Teri E
Clinical pharmacology and therapeutics. 2013;.
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Full-text held externally
- PMID: 24060820
- UKPMCID: 24060820
- DOI: 10.1038/clpt.2013.186
Abstract
The International Tamoxifen Pharmacogenomics Consortium (ITPC) was established to address the controversy over CYP2D6 status and clinical outcomes in tamoxifen therapy. We performed a meta-analysis on data from 4,973 tamoxifen treated patients (twelve globally-distributed sites). Using strict eligibility requirements (postmenopausal women with estrogen receptor (ER) 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: HR=1.25; 95% CI 1.06, 1.47; P=0.009). However, CYP2D6 was not statistically significant when tamoxifen duration, menopausal status, and annual follow-up were not specified (Criterion 2, n=2443; 49%; P=0.25) nor when no exclusions were applied (Criterion 3, n=4935; 99%; 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.Clinical Pharmacology & Therapeutics (2013); accepted article preview online 23 September 2013 doi:10.1038/clpt.2013.186.
Bibliographic metadata
- Province, Michael A
- Goetz, Matthew P
- Brauch, Hiltrud
- Flockhart, David A
- Hebert, Joan M
- Whaley, Ryan
- Suman, Vera J
- Schroth, Werner
- Winter, Stefan
- Zembutsu, Hitoshi
- Mushiroda, Taisei
- Newman, William G
- Michael Lee, Ming-Ta
- Ambrosone, Christine B
- Beckmann, Matthias W
- Choi, Ji-Yeob
- Dieudonné, Anne-Sophie
- Fasching, Peter A
- Ferraldeschi, Roberta
- Gong, Li
- Haschke-Becher, Elisabeth
- Howell, Anthony
- Jordan, Lee B
- Hamann, Ute
- Kiyotani, Kazuma
- Krippl, Peter
- Lambrechts, Diether
- Latif, Ayse
- Langsenlehner, Uwe
- Lorizio, Wendy
- Neven, Patrick
- Nguyen, Anne T
- Park, Byeong-Woo
- Purdie, Colin A
- Quinlan, Philip
- Renner, Wilifried
- Schmidt, Marcus
- Schwab, Matthias
- Shin, Jae-Gook
- Stingl, Julia C
- Wegman, Pia
- Wingren, Sten
- Wu, Alan H B
- Ziv, Elad
- Zirpoli, Gary
- Thompson, Alastair M
- Jordan, V Craig
- Nakamura, Yusuke
- Altman, Russ B
- Ames, Matthew M
- Weinshilboum, Richard M
- Eichelbaum, Michel
- Ingle, James N
- Klein, Teri E