Antiestrogens, aromatase inhibitors, and apoptosis in breast cancer

Vitam Horm. 2005;71:201-37. doi: 10.1016/S0083-6729(05)71007-4.


Antiestrogens have been the therapeutic agents of choice for breast cancer patients whose tumors express estrogen receptors, regardless of menopausal status. Unfortunately, many patients will eventually develop resistance to these drugs. Antiestrogens primarily act by preventing endogenous estrogen from activating estrogen receptors and promoting cell growth, which can ultimately lead to tumor cell death. Understanding the mechanisms by which antiestrogens cause cell death or apoptosis is critical to our efforts to develop ways to circumvent resistance. This article focuses on antiestrogen-induced apoptosis both in vitro and in vivo. We review the clinical utility of both antiestrogens and aromatase inhibitors and their apoptogenic mechanisms in cell culture models. Among the key signaling components discussed are the roles of Bcl-2 family members, several cytokines, and their receptors, p53, nuclear factor kappa B (NFkappaB), IRF-1, phosphatidylinositol 3-kinase (PI3K)/Akt, and specific caspases. Finally, we discuss the evidence supporting a role for apoptotic defects in acquired and de novo antiestrogen resistance.

Publication types

  • Review

MeSH terms

  • Animals
  • Apoptosis* / drug effects
  • Aromatase Inhibitors* / therapeutic use
  • Breast Neoplasms* / drug therapy
  • Drug Resistance, Neoplasm
  • Estrogen Antagonists* / therapeutic use
  • Estrogens / physiology
  • Female
  • Humans
  • Receptors, Estrogen / physiology


  • Aromatase Inhibitors
  • Estrogen Antagonists
  • Estrogens
  • Receptors, Estrogen