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The effect of rs5758550 on CYP2D6*2 phenotype and formation of endoxifen in breast cancer patients using tamoxifen

    Anabel B Sanchez-Spitman

    Leiden Network for Personalised Therapeutics, Department of Clinical Pharmacy & Toxicology, Leiden University Medical Center, Leiden, The Netherlands

    ,
    Dirk-Jan AR Moes

    Leiden Network for Personalised Therapeutics, Department of Clinical Pharmacy & Toxicology, Leiden University Medical Center, Leiden, The Netherlands

    ,
    Hans Gelderblom

    Department of Medical Oncology, Leiden University Medical Center, Leiden, The Netherlands

    ,
    Vincent O Dezentjé

    Department of Medical Oncology, Reinier de Graaf, Delft, The Netherlands

    ,
    Jesse J Swen

    Leiden Network for Personalised Therapeutics, Department of Clinical Pharmacy & Toxicology, Leiden University Medical Center, Leiden, The Netherlands

    &
    Henk-Jan Guchelaar

    *Author for correspondence:

    E-mail Address: h.j.guchelaar@lumc.nl

    Leiden Network for Personalised Therapeutics, Department of Clinical Pharmacy & Toxicology, Leiden University Medical Center, Leiden, The Netherlands

    Published Online:https://doi.org/10.2217/pgs-2017-0080

    Aim:CYP2D6*2 is considered fully active, but it has been suggested that it only happens in the presence of rs5758550. This study aims to elucidate the impact of this enhancer. Materials & methods: DNA and blood samples from women enrolled in the CYPTAM study (NTR1509) were analyzed. Fourteen CYP2D6*2 carriers without the enhancer were reclassified. The relationship of CYP2D6 phenotypes and drug levels was studied. Results: After correction for the absence of the enhancer, the correlation between CYP2D6 phenotypes and endoxifen did not improve (R2: 0.290 vs 0.279). No difference was observed in mean concentrations between CYP2D6*2 individuals with and without the enhancer. Conclusion: The rs5758550 enhancer does not lead to improved prediction of endoxifen levels in breast cancer patients.

    Papers of special note have been highlighted as: • of interest; •• of considerable interest

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