New insights into the metabolism of tamoxifen and its role in the treatment and prevention of breast cancer

Steroids. 2007 Nov;72(13):829-42. doi: 10.1016/j.steroids.2007.07.009. Epub 2007 Jul 27.


The metabolism of tamoxifen is being redefined in the light of several important pharmacological observations. Recent studies have identified 4-hydroxy N-desmethyltamoxifen (endoxifen) as an important metabolite of tamoxifen necessary for antitumor actions. The metabolite is formed through the enzymatic product of CYP2D6 which also interacts with specific selective serotonin reuptake inhibitors (SSRIs) used to prevent the hot flashes observed in up to 45% of patients taking tamoxifen. Additionally, the finding that enzyme variants of CYP2D6 do not promote the metabolism of tamoxifen to endoxifen means that significant numbers of women might not receive optimal benefit from tamoxifen treatment. Clearly these are particularly important issues not only for breast cancer treatment but also for selecting premenopausal women, at high risk for breast cancer, as candidates for chemoprevention using tamoxifen.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Antineoplastic Agents, Hormonal / metabolism*
  • Antineoplastic Agents, Hormonal / therapeutic use
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / prevention & control
  • Female
  • Humans
  • Molecular Mimicry
  • Selective Estrogen Receptor Modulators / metabolism*
  • Selective Estrogen Receptor Modulators / therapeutic use
  • Tamoxifen / metabolism*
  • Tamoxifen / therapeutic use


  • Antineoplastic Agents, Hormonal
  • Selective Estrogen Receptor Modulators
  • Tamoxifen