Genotoxicity of steroidal estrogens

Trends Endocrinol Metab. 2004 Jul;15(5):211-4. doi: 10.1016/j.tem.2004.05.007.


The molecular mechanisms underlying the development of breast cancer in general, and estrogen-associated breast carcinogenesis in particular, are not completely understood. There are three mechanisms considered responsible for the carcinogenicity of estrogens in the human breast: (i) receptor-mediated hormonal activity, which stimulates cellular proliferation, resulting in more opportunities for accumulation of the genetic damage that leads to carcinogenesis; (ii) a cytochrome P450-mediated metabolic activation, which elicits direct genotoxic effects by increasing mutation rates; and (iii) the induction of aneuploidy by estrogen. In this article, we concentrate on discussing the role of estrogen receptors and the metabolic activation of 17beta-estradiol (E(2)) as mechanisms of breast cancer initiation.

Publication types

  • Review

MeSH terms

  • Animals
  • Breast Neoplasms / etiology*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / physiopathology*
  • Estradiol / physiology*
  • Female
  • Humans
  • Receptors, Estrogen / physiology*


  • Receptors, Estrogen
  • Estradiol