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1. Pharmacogenomics. 2012 Apr;13(6):691-7.

Use of CYP2D6 genotyping in practice: tamoxifen dose adjustment.

Walko CM, McLeod H.

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

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.

PMID: 22515611 [PubMed - in process]