کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
3979835 1257378 2015 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Individualization of tamoxifen therapy: Much more than just CYP2D6 genotyping
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی تومور شناسی
پیش نمایش صفحه اول مقاله
Individualization of tamoxifen therapy: Much more than just CYP2D6 genotyping
چکیده انگلیسی


• CYP2D6 genotyping is an oversimplified approach for tamoxifen individualization.
• Tamoxifen pharmacokinetics are influenced by many genetic and environmental factors.
• There is increasing evidence supporting the important role of endoxifen.
• TDM is likely to be the optimal strategy for tamoxifen individualization.
• Phenotyping strategies may be useful in determining the initial tamoxifen dose.

Clinical response to tamoxifen varies widely among women treated with this drug for hormone receptor-positive breast cancer. The principal active metabolite – endoxifen – is generated through hepatic metabolism of tamoxifen, with key roles for cytochrome P450 (CYP) CYP2D6 and CYP3A. By influencing endoxifen formation, genetic variants of CYP2D6 may affect response to tamoxifen. After a decade of research, examining the effects of CYP2D6 genetic variants on tamoxifen efficacy, there is still no agreement on the clinical utility of CYP2D6 genotype as biomarker for the prediction of breast cancer outcome, because studies revealed conflicting results. However, tamoxifen metabolism is complex and involves several other drug-metabolizing enzymes. Genetic variants of other CYP enzymes, including CYP3A4 and CYP2C9/19, as well as co-medication interfering with the metabolic activity of CYP2D6 and CYP3A4 have been shown to affect endoxifen concentrations and may also contribute to the variability in response to tamoxifen. Phenotyping strategies can predict endoxifen exposure more accurately than CYP2D6 genotype, but do not take into account all factors influencing endoxifen exposure. Therapeutic drug monitoring (TDM) is likely to be the optimal strategy for individualization of tamoxifen treatment. According to a growing amount of literature, endoxifen concentration seems to be a predictor of clinical outcome. The relationship between endoxifen levels and breast cancer outcomes has to be replicated and confirmed and the value of TDM should be evaluated in prospective clinical trials. Caution is advised regarding the concomitant use of medications which could interact with tamoxifen, including inhibitors and inducers of CYP enzymes.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cancer Treatment Reviews - Volume 41, Issue 3, March 2015, Pages 289–299
نویسندگان
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