Molecular mechanisms of endocrine resistance and their implication in the therapy of breast cancer

Biochim Biophys Acta. 2009 Jan;1795(1):62-81. doi: 10.1016/j.bbcan.2008.08.003. Epub 2008 Aug 29.


The use of endocrine agents is a safe and effective treatment in the management of hormone-sensitive breast cancer. Unfortunately, sooner or later, tumor cells develop resistance to endocrine manipulation making useless this approach. During the last decade, new molecules and intracellular signaling pathways involved in endocrine resistance have been identified. Several studies have documented that estrogen receptor signaling may maintain a pivotal role in the tumor growth despite the failure of a previous hormonal treatment. In this review we will discuss the general principles for optimizing the choice of endocrine therapy based on an understanding of the molecular mechanisms responsible for resistance to the different anti-hormonal agents.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents, Hormonal / therapeutic use*
  • Breast Neoplasms / diagnosis
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / genetics*
  • Drug Resistance, Neoplasm / genetics*
  • Estradiol / physiology
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Hormone Antagonists / therapeutic use
  • Humans
  • Models, Biological
  • Mutation / physiology
  • Neoplasms, Hormone-Dependent / drug therapy
  • Neoplasms, Hormone-Dependent / genetics
  • Receptors, Estrogen / genetics
  • Receptors, Estrogen / metabolism
  • Receptors, Estrogen / physiology
  • Selective Estrogen Receptor Modulators / therapeutic use


  • Antineoplastic Agents, Hormonal
  • Hormone Antagonists
  • Receptors, Estrogen
  • Selective Estrogen Receptor Modulators
  • Estradiol