期刊
PHARMACOGENOMICS JOURNAL
卷 9, 期 4, 页码 258-264出版社
SPRINGERNATURE
DOI: 10.1038/tpj.2009.14
关键词
tamoxifen; cytochrome P450 2D6; pharmacogenetics; compliance; adherence
资金
- Indiana University GCRC [M01RR00750]
- University of Michigan GCRC [M01-RR00042]
- Georgetown University [M01-RR13297]
- National Institute of General Medical Sciences (Bethesda, MD, USA)
- Damon Runyon Cancer Research Foundation (VS)
- Fashion Footwear Charitable Foundation of New York/QVC Presents Shoes on Sale (DFH)
- Breast Cancer Research Foundation [N003173]
- National Center for Research Resources (NCRR) [M01-RR000042]
- National Institutes of Health (NIH)
- [U-01 GM61373]
- [T-32 GM007767]
The selective estrogen receptor modulator tamoxifen is routinely used for treatment and prevention of estrogen-receptor-positive breast cancer. Studies of tamoxifen adherence suggest that over half of patients discontinue treatment before the recommended 5 years. We hypothesized that polymorphisms in CYP2D6, the enzyme responsible for tamoxifen activation, predict for tamoxifen discontinuation. Tamoxifen-treated women (n = 297) were genotyped for CYP2D6 variants and assigned a 'score' based on predicted allele activities from 0 (no activity) to 2 (high activity). Correlation between CYP2D6 score and discontinuation rates at 4 months was tested. We observed a strong nonlinear correlation between higher CYP2D6 score and increased rates of discontinuation (r(2) = 0.935, P = 0.018). These data suggest that presence of active CYP2D6 alleles may predict for higher likelihood of tamoxifen discontinuation. Therefore, patients who may be most likely to benefit from tamoxifen may paradoxically be most likely to discontinue treatment prematurely. The Pharmacogenomics Journal (2009) 9, 258-264; doi: 10.1038/tpj.2009.14; published online 5 May 2009
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