Rat models of 17β-estradiol-induced mammary cancer reveal novel insights into breast cancer etiology and prevention

Physiol Genomics. 2018 Mar 1;50(3):215-234. doi: 10.1152/physiolgenomics.00105.2017. Epub 2018 Jan 26.


Numerous laboratory and epidemiologic studies strongly implicate endogenous and exogenous estrogens in the etiology of breast cancer. Data summarized herein suggest that the ACI rat model of 17β-estradiol (E2)-induced mammary cancer is unique among rodent models in the extent to which it faithfully reflects the etiology and biology of luminal types of breast cancer, which together constitute ~70% of all breast cancers. E2 drives cancer development in this model through mechanisms that are largely dependent upon estrogen receptors and require progesterone and its receptors. Moreover, mammary cancer development appears to be associated with generation of oxidative stress and can be modified by multiple dietary factors, several of which may attenuate the actions of reactive oxygen species. Studies of susceptible ACI rats and resistant COP or BN rats provide novel insights into the genetic bases of susceptibility and the biological processes regulated by genetic determinants of susceptibility. This review summarizes research progress resulting from use of these physiologically relevant rat models to advance understanding of breast cancer etiology and prevention.

Keywords: ACI rat; BN rat; breast cancer; diet; environment; estradiol; estrogen; genetics; hormones; mammary cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Animals
  • Breast Neoplasms / etiology*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / prevention & control*
  • Carcinogenesis / pathology
  • Disease Models, Animal
  • Estradiol / adverse effects*
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Mammary Neoplasms, Animal / pathology*


  • Estradiol