Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
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SHR Neuro Krebs Kardio Lipid Stoffw Microb
Province, MA; Goetz, MP; Brauch, H; Flockhart, DA; Hebert, JM; Whaley, R; Suman, VJ; Schroth, W; Winter, S; Zembutsu, H; Mushiroda, T; Newman, WG; Lee, MT; Ambrosone, CB; Beckmann, MW; Choi, JY; Dieudonné, AS; Fasching, PA; Ferraldeschi, R; Gong, L; Haschke-Becher, E; Howell, A; Jordan, LB; Hamann, U; Kiyotani, K; Krippl, P; Lambrechts, D; Latif, A; Langsenlehner, U; Lorizio, W; Neven, P; Nguyen, AT; Park, BW; Purdie, CA; Quinlan, P; Renner, W; Schmidt, M; Schwab, M; Shin, JG; Stingl, JC; Wegman, P; Wingren, S; Wu, AH; Ziv, E; Zirpoli, G; Thompson, AM; Jordan, VC; Nakamura, Y; Altman, RB; Ames, MM; Weinshilboum, RM; Eichelbaum, M; Ingle, JN; Klein, TE; International Tamoxifen Pharmacogenomics Consortium.
CYP2D6 genotype and adjuvant tamoxifen: meta-analysis of heterogeneous study populations.
Clin Pharmacol Ther. 2014; 95(2):216-227
Doi: 10.1038/clpt.2013.186
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- Co-Autor*innen der Med Uni Graz
- Langsenlehner Uwe
- Renner Wilfried
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- 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Aged -
- Antineoplastic Agents, Hormonal - pharmacokinetics
- Antineoplastic Agents, Hormonal - therapeutic use
- Breast Neoplasms - drug therapy
- Breast Neoplasms - genetics
- Cytochrome P-450 CYP2D6 - genetics
- Female -
- Genetic Variation - genetics
- Genotype -
- Humans -
- Menopause -
- Middle Aged -
- Pharmacogenetics - methods
- Survival Analysis -
- Tamoxifen - pharmacokinetics
- Tamoxifen - therapeutic use
- Treatment Outcome -