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Use of CYP2D6 genotyping in practice: tamoxifen dose adjustment

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UNC Eshelman School of Pharmacy, Division of Pharmacotherapy & Experimental Therapeutics, University of North Carolina at Chapel Hill, NC, USA.

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Email the corresponding author at cwalko@email.unc.edu

Howard McLeod

UNC Eshelman School of Pharmacy, Division of Pharmacotherapy & Experimental Therapeutics, University of North Carolina at Chapel Hill, NC, USA

Institute of Pharmacogenomics & Individualized Therapy, University of North Carolina at Chapel Hill, NC, USA

Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, NC, USA

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Published Online:19 Apr 2012https://doi.org/10.2217/pgs.12.27

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Abstract

Tamoxifen is a selective estrogen-receptor modulator that is commonly utilized in the treatment and prevention of endocrine receptor-positive breast cancer. Ultimate conversion of the parent drug by the enzyme CYP2D6 to the active metabolite, endoxifen, is required for tamoxifen to exert its anticancer effects. CYP2D6 exists in varying concentrations across individuals due, in part, to genetic variation. Lower concentrations of endoxifen have been associated with inferior breast cancer outcomes in numerous retrospective trials. In an effort to increase the endoxifen concentrations, three prospective trials have assessed different methods of increasing tamoxifen dose based on patient CYP2D6 genotypes. All three demonstrated the ability to increase endoxifen concentrations using tamoxifen at a dose of 30 or 40 mg daily. These positive findings support future investigations to determine, not only the clinical benefit of genotype-guided therapy, but also the optimal dose needed for individual patients.

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Papers of special note have been highlighted as: ▪ of interest ▪▪ of considerable interest

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Vol. 13, No. 6

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Published online 19 April 2012

Published in print April 2012

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Financial & competing interests disclosure

This work was supported by the UNC Carolina Partnership, the UNC University Cancer Research Fund and UL1RR025747 from the National Center for Research Resources. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

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