Obesity, aromatase and breast cancer

After the menopausal transition, the ovaries cease to make estrogens, yet the incidence of breast cancer increases and the majority of these tumors are estrogen receptor positive. So, where is the estrogen driving this tumor development coming from? Several extragonadal sites, such as bone, brain and adipose tissue, synthesize estrogens from circulating C19 steroids. The largest of these depots is the adipose tissue, and increased BMI is associated with increased breast cancer risk as well as increased circulating estrogen levels. The mechanisms linking obesity to breast cancer risk are not yet completely understood, although it is widely assumed that estrogens produced in the fat play a role. This article aims to provide a comprehensive overview of the regulation of aromatase expression in the breast adipose tissue in response to fat and tumor-derived factors, as well as new evidence suggesting that breast-specific inhibition of aromatase may be possible.