Breast cancer incidence and mortality increase dramatically after the age of 65. However, some tumors grow more slowly and progression is less aggressive in the elderly. The goal of this project is to develop models to study the mechanisms involved in spontaneous breast cancer development and progression in aged female rats. Progression of these cancers involves loss of tumor suppressor gene expression and reduced expression of estrogen receptors. About one-half of spontaneous tumors in aged rats have reduced methylation of the first exon of the estrogen receptor gene. Contralateral normal mammary tissue from these animals and mammary tissue from tumor free aged animals also have reduced methylation suggesting that hypomethylation at this site is associated with tumor initiation.
