Annals of Oncology Advance Access originally published online on April 11, 2008
Annals of Oncology 2008 19(8):1423-1429; doi:10.1093/annonc/mdn155
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breast cancer |
Association between CYP2D6 *10 genotype and survival of breast cancer patients receiving tamoxifen treatment
1 Breast Center
2 Department of Traditional Chinese Medicine, Beijing Cancer Hospital & Institute, Peking University School of Oncology, Beijing, People's Republic of China
3 Department of Biochemistry and Molecular Biology, Beijing Cancer Hospital & Institute, Peking University School of Oncology, Beijing, People's Republic of China
* Correspondence to: Dr Y. Xie and Dr P. Li, Beijing Cancer Hospital and Institute, Peking University School of Oncology, 100036, Beijing, P. R. China; Tel: +86-10-88196362; E-mail: zlxyt2{at}bjmu.edu.cn or lppma123{at}yahoo.com.cn
Background: Human cytochrome P450 2D6 (CYP2D6) genotype may affect the efficacy of tamoxifen treatment in Caucasian women with breast cancer. The most common polymorphism of CYP2D6 in Chinese women is variant 10 (188 C to T).
Patients and methods: Tamoxifen and 4-hydroxytamoxifen (4OHtam) were measured in the serum of 37 women with breast cancer who were receiving tamoxifen treatment. The association between CYP2D6 *10 genotype and survival was determined in a cohort of 293 women with breast cancer who received tamoxifen (n = 152) or who did not (n = 141).
Results: The serum 4OHtam concentrations were significantly lower in women with the CYP2D6 *10 homozygous variant T/T genotype than in those with the homozygous wild-type C/C genotype (P = 0.04). Among tamoxifen-treated women, women with the T/T genotype had a significantly worse disease-free survival (DFS) than those with the C/C or C/T genotype, and the T/T genotype remained an independent prognostic factor of DFS in multivariate analysis (hazard ratio = 4.7; 95% confidence interval = 1.1–20.0; P = 0.04). Among women who did not receive tamoxifen, there was no significant association between CYP2D6 *10 genotype and survival.
Conclusion: In tamoxifen-treated patients, women with the CYP2D6 *10 T/T genotype have a lower 4OHtam level in the serum and a worse clinical outcome.
Key words: breast cancer, CYP2D6 *10 genotype, survival, tamoxifen
These authors have contributed equally to the work. Received for publication November 11, 2007. Revision received March 10, 2008. Accepted for publication March 10, 2008.
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