Pharmacogenetics of tamoxifen

Who should undergo CYP2D6 genetic testing?

Michaela J. Higgins, James M. Rae, David A. Flockhart, Daniel F. Hayes, Vered Stearns

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

Many women with hormone receptor-positive breast cancer will receive tamoxifen at some point in their treatment course. Tamoxifen is biotransformed to the potent antiestrogen endoxifen almost exclusively through the cytochrome P450 (CYP) 2D6 isoform. Although prospective data are lacking, the balance of evidence available currently suggests that a single nucleotide polymorphism in the CYP2D6 gene, particularly the presence of 2 null alleles, predicts for reduced tamoxifen metabolism and possibly poorer outcome than expected in patients with a wild-type genotype. Studies evaluating the impact of genetic polymorphisms that result in CYP2D6 with reduced or no activity on long-term outcome have been mostly retrospective and conducted on archival tissues or those obtained previously in prospective studies of tamoxifen. Until data are available from retrospective examinations of the large prospective trials already conducted, or adequately powered prospective analyses, transforming this information into guidelines for individual patients remains challenging. The authors do not currently recommend routine testing for CYP2D6 genotype for making clinical decisions regarding tamoxifen. Use of concomitant strong or intermediate inhibitors of CYP2D6 should be avoided when alternate medications are available. Ongoing research is directed toward identifying other polymorphisms that may influence the efficacy and safety of tamoxifen, other hormonal agents, and chemotherapies used to treat breast cancer. The hope is that in the future, not only tumor-associated factors but also germ-line host genetics can be used to determine whether a woman should receive treatment, and with which specific agents, to prevent breast cancer recurrence or death or avoid drug-related toxicities.

Original languageEnglish
Pages (from-to)203-213
Number of pages11
JournalJNCCN Journal of the National Comprehensive Cancer Network
Volume7
Issue number2
StatePublished - Feb 2009

Fingerprint

Cytochrome P-450 CYP2D6
Pharmacogenetics
Genetic Testing
Tamoxifen
Breast Neoplasms
Genotype
Estrogen Receptor Modulators
Genetic Polymorphisms
Drug-Related Side Effects and Adverse Reactions
Germ Cells
Single Nucleotide Polymorphism
Protein Isoforms
Alleles
Hormones
Prospective Studies
Guidelines
Safety
Recurrence
Drug Therapy
Therapeutics

Keywords

  • Breast cancer
  • CYP2D6
  • Endocrine treatment
  • Pharmacogenetics
  • Tamoxifen metabolism

ASJC Scopus subject areas

  • Oncology

Cite this

Higgins, M. J., Rae, J. M., Flockhart, D. A., Hayes, D. F., & Stearns, V. (2009). Pharmacogenetics of tamoxifen: Who should undergo CYP2D6 genetic testing? JNCCN Journal of the National Comprehensive Cancer Network, 7(2), 203-213.

Pharmacogenetics of tamoxifen : Who should undergo CYP2D6 genetic testing? / Higgins, Michaela J.; Rae, James M.; Flockhart, David A.; Hayes, Daniel F.; Stearns, Vered.

In: JNCCN Journal of the National Comprehensive Cancer Network, Vol. 7, No. 2, 02.2009, p. 203-213.

Research output: Contribution to journalArticle

Higgins, MJ, Rae, JM, Flockhart, DA, Hayes, DF & Stearns, V 2009, 'Pharmacogenetics of tamoxifen: Who should undergo CYP2D6 genetic testing?', JNCCN Journal of the National Comprehensive Cancer Network, vol. 7, no. 2, pp. 203-213.
Higgins, Michaela J. ; Rae, James M. ; Flockhart, David A. ; Hayes, Daniel F. ; Stearns, Vered. / Pharmacogenetics of tamoxifen : Who should undergo CYP2D6 genetic testing?. In: JNCCN Journal of the National Comprehensive Cancer Network. 2009 ; Vol. 7, No. 2. pp. 203-213.
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