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Pharmacogenetics and breast cancer endocrine therapy: CYP2D6 as a predictive factor for tamoxifen metabolism and drug response?

Published online by Cambridge University Press:  20 November 2008

Vered Stearns  and
James M. Rae
Vered Stearns*
Affiliation:
Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, USA.
James M. Rae
Affiliation:
University of Michigan Comprehensive Cancer Center, Ann Arbor, MI, USA.
*
*Corresponding author: Vered Stearns, Bunting-Blaustein Cancer Research Building, 1650 Orleans Street, Room 145, Baltimore, MD 21231-1000, USA. Tel: +1 443 287 6489; Fax: +1 410 955 0125; E-mail: vstearn1@jhmi.edu
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Abstract

The identification of genetic polymorphisms that influence the efficacy and safety of therapies for breast cancer may allow future treatments to be individualised based not only on tumour characteristics but also on host genetics. Genetic factors that affect the metabolism, efficacy and safety of tamoxifen, one of the most common drugs used for the treatment and prevention of breast cancer, have received particular attention. Cytochrome P450 2D6 (CYP2D6) is crucial in the metabolism of tamoxifen to its active metabolite endoxifen. Women with genetic variants of CYP2D6 or who take drugs that inhibit the enzyme have low endoxifen plasma concentrations and may show reduced benefits to tamoxifen treatment. CYP2D6 polymorphisms and variants in other candidate genes may also influence secondary benefits and side effects of tamoxifen. Here, we summarise data suggesting that CYP2D6 status may be an important predictor of the benefits of tamoxifen to an individual; in addition, we briefly discuss the role of variants in other candidate genes. Whether CYP2D6 status should be determined prior to initiating tamoxifen therapy is currently under debate and may be appropriate only for select women who are candidates for tamoxifen alone but for whom alternative standard options are available.

Type
Review Article
Information
Expert Reviews in Molecular Medicine , Volume 10 , October 2008 , e34
Copyright
Copyright © Cambridge University Press 2008

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References

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Further reading, resources and contacts

Stearns, V., Davidson, N.E. and Flockhart, D.A. (2004) Pharmacogenetics in the treatment of breast cancer. Pharmacogenomics J 4, 143-153CrossRefGoogle ScholarPubMed
http://medicine.iupui.edu/flockhart/Google Scholar