Antagonistic and agonistic effects of tamoxifen: significance in human cancer

Semin Oncol. 1997 Feb;24(1 Suppl 1):S1-71-S1-80.


Tamoxifen is a substituted triphenylethylene antiestrogen used in the adjuvant therapy and chemoprevention of breast cancer. The antiestrogenic activity of the compound has been attributed to its metabolism to an active 4-hydroxy derivative and the avid binding of the active metabolite to the estrogen receptor. Receptor binding of the antiestrogen alters the transcriptional activity normally attributed to the estradiol-bound estrogen receptor. Tamoxifen is both an antagonist and an agonist of the estrogen receptor. However, a molecular explanation exists for this apparent paradox. The dual action is a function of the estrogen receptor complex present in a particular cell or tissue. If a cell type requires activating factors 1 and 2 of the estrogen receptor to be functioning concurrently, tamoxifen is antagonistic. However, if a cell or tissue requires only activating factor 1 to interact with transcription factors at the promoter, tamoxifen is agonistic. The implication is that the investigators must understand the fundamental biology of the estrogen receptor complex in a tissue context before one can predict tissue activity of tamoxifen.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents, Hormonal / metabolism
  • Antineoplastic Agents, Hormonal / pharmacology*
  • Endometrial Neoplasms / chemically induced
  • Endometrium / drug effects
  • Female
  • Humans
  • Receptors, Estrogen / agonists*
  • Receptors, Estrogen / antagonists & inhibitors*
  • Tamoxifen / metabolism
  • Tamoxifen / pharmacology*


  • Antineoplastic Agents, Hormonal
  • Receptors, Estrogen
  • Tamoxifen