کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
3909181 1251208 2011 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Tamoxifen, cytochrome P450 genes and breast cancer clinical outcomes
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی زنان، زایمان و بهداشت زنان
پیش نمایش صفحه اول مقاله
Tamoxifen, cytochrome P450 genes and breast cancer clinical outcomes
چکیده انگلیسی

Tamoxifen has a key role in the management of women with hormone receptor (HR) positive breast cancer. It is the endocrine treatment of choice in premenopausal women with HR positive breast cancer and is also clinically indicated in significant numbers of post-menopausal women who have relative contraindications to aromatase inhibitors. Tamoxifen is a pro-drug that is metabolised to its active metabolites by the cytochrome P450 (CYP) enzymes including CYP2D6, CYP3A, CYP2B6, and CYP2C19. The CYP genes are polymorphic resulting in variable enzyme activity.Retrospective clinical data suggests that specific single nucleotide polymorphisms (SNPs) of CYP2D6 can lead to null or reduced enzyme activity resulting in worse outcomes for those individuals when treated with tamoxifen for HR positive breast cancer. There is however a lack of robust prospective clinical data on this subject. Commercial tests are now available for the genotyping of CYP2D6 with the aim of individualisation of tamoxifen therapy for patients with HR positive breast cancer. Selective serotonin reuptake inhibitor antidepressant drugs such as paroxetine and fluoxetine have also been used to manage tamoxifen induced hot flushes. These drugs potently inhibit the metabolism of tamoxifen by CYP2D6 and thus potentially may lessen the efficacy of tamoxifen. The genetic variations in other enzymes involved in tamoxifen metabolism (CYP3A, CYP2B6, CYP2C19) do not appear to cause any meaningful difference in the efficacy of tamoxifen.This review article will summarize the available published breast cancer data on the interaction between the relevant SNPs for CYP2D6, CYP3A, CYP2B6, and CYP2C19 and the efficacy of tamoxifen, their role in individualisation of hormonal therapy and the role of the commercially available genotyping kits.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: The Breast - Volume 20, Issue 2, April 2011, Pages 111–118
نویسندگان
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