Epigenetic regulation in estrogen receptor positive breast cancer--role in treatment response

J Mammary Gland Biol Neoplasia. 2010 Mar;15(1):35-47. doi: 10.1007/s10911-010-9166-0. Epub 2010 Jan 27.


Recent advances in breast cancer treatment have allowed increasing numbers of patients with estrogen receptor (ER) positive (+) breast cancer to receive various forms of endocrine therapy. Unfortunately, de novo and acquired resistance to endocrine therapy remains a major challenge in the clinic. A number of possible mechanisms for drug resistance have been described, which include activation of growth factor receptor pathways, overexpression of ER coactivators, and metabolic resistance due to polymorphisms in metabolizing enzymes. While many of these changes are caused by genetic alterations, there is also increasing evidence to implicate epigenetic gene regulatory mechanisms in the development of endocrine resistance. Since epigenetic modifications are easier to reverse than genetic mutations, they are appealing therapeutic targets, and thus future improvements in medical care for breast cancer patients will depend upon a better understanding of the roles epigenetic modifications play in endocrine resistance. In this review we will focus on recent advances made in the understanding of epigenetic gene regulation in estrogen response and endocrine resistance in breast cancer. We will also summarize current clinical-translational advances in epigenetic therapy, and discuss potential future clinical use of epigenetic changes as therapeutic targets, especially with respect to endocrine treatment.

Publication types

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

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use
  • Antineoplastic Agents, Hormonal / therapeutic use
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism
  • Drug Resistance, Neoplasm
  • Epigenesis, Genetic / physiology*
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Histone Deacetylase Inhibitors / therapeutic use
  • Humans
  • Receptors, Estrogen / genetics
  • Receptors, Estrogen / metabolism*
  • Receptors, Progesterone / genetics
  • Receptors, Progesterone / metabolism
  • Treatment Outcome


  • Antineoplastic Agents
  • Antineoplastic Agents, Hormonal
  • Histone Deacetylase Inhibitors
  • Receptors, Estrogen
  • Receptors, Progesterone