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CYP2D6 polymorphisms and tamoxifen: therapeutic perspectives in the management of hormonodependent breast cancer patients


Bulletin du Cancer. Volume 97, Number 3, 311-20, mars 2010, Synthèse

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Author(s) : J Barrière, J-L Formento, G Milano, J-M Ferrero

Summary : Tamoxifen is a prodrug mainly metabolized by the CY2D6 cytochrome. More than 80 variants of the CYP2D6 gene have been identified. They predict four different enzymatic phenotypes: ultra-rapid metabolizers (UM), extensive metabolizers (EM), intermediate metabolizers (IM) and poor metabolizers (PM). Six retrospectives studies suggest a link between some polymorphisms of the CYP2D6 and tamoxifen efficacy and two studies have found no statistically significant data. Today, level of proof remains insufficient to recommend the testing of a patient’s genotype before tamoxifen prescription. Designing prospective studies is necessary before considering therapy strategies based on pharmacogenetics data. In pre-menopausal breast cancer PM or IM patients, an increase in dosage of tamoxifen or a treatment with LH-RH analogues with aromatase inhibitors (AI) may be beneficial instead of the actual recommendations of a 5-year tamoxifen therapy. In postmenopausal EM patients, tamoxifen may be as efficient as AI. In post-menopausal PM patients, a switch strategy may be inferior to a 5-year IA strategy, which would therefore be the standard of care.

Keywords : tamoxifen, CYP2D6, pharmacogenetics, breast cancer, hormonotherapy, adjuvant therapy

 

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