Tamoxifen pharmacogenomics: the role of CYP2D6 as a predictor of drug response

Clin Pharmacol Ther. 2008 Jan;83(1):160-6. doi: 10.1038/sj.clpt.6100367. Epub 2007 Sep 19.


Tamoxifen continues to be a standard endocrine therapy for the prevention and treatment of estrogen receptor (ER)-positive breast cancer. Tamoxifen can be considered a classic "pro-drug," requiring metabolic activation to elicit pharmacological activity. CYP2D6 is the rate-limiting enzyme catalyzing the conversion of tamoxifen into metabolites with significantly greater affinity for the ER and greater ability to inhibit cell proliferation. Both genetic and environmental (drug-induced) factors that alter CYP2D6 enzyme activity directly affect the concentrations of the active tamoxifen metabolites and the outcomes of patients receiving adjuvant tamoxifen. The a priori knowledge of the pharmacogenetic variation known to abrogate CYP2D6 enzyme activity may provide a means by which the hormonal therapy of breast cancer can be individualized.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Antineoplastic Agents, Hormonal / metabolism*
  • Antineoplastic Agents, Hormonal / therapeutic use
  • Biomarkers / metabolism
  • Biotransformation
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / enzymology
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology
  • Cell Proliferation / drug effects
  • Cytochrome P-450 CYP2D6 / genetics
  • Cytochrome P-450 CYP2D6 / metabolism*
  • Cytochrome P-450 CYP2D6 Inhibitors
  • Drug Interactions
  • Enzyme Inhibitors / pharmacology
  • Female
  • Genetic Variation*
  • Genotype
  • Humans
  • Patient Selection
  • Pharmacogenetics*
  • Phenotype
  • Tamoxifen / metabolism*
  • Tamoxifen / therapeutic use
  • Treatment Outcome


  • Antineoplastic Agents, Hormonal
  • Biomarkers
  • Cytochrome P-450 CYP2D6 Inhibitors
  • Enzyme Inhibitors
  • Tamoxifen
  • Cytochrome P-450 CYP2D6