Aromatase, breast cancer and obesity: a complex interaction.

Obesity has been associated with abnormally high expression of the enzyme aromatase in the breast, increased local estrogen production, and predisposition to breast hyperplasia and cancer. Increased adiposity in postmenopausal women may trigger signaling pathways that induce aromatase expression. In breast adipose fibroblasts, increased TNF production may induce the distal aromatase promoter, whereas increased local PGE(2) production may induce the proximal promoter region. We review here the mechanisms that control aromatase gene expression in breast adipose tissue, and the paracrine interactions between malignant breast epithelial cells and the surrounding adipose fibroblasts. Systematic characterization of these signaling pathways will facilitate the identification of potential drug targets to selectively reduce aromatase expression and excessive estrogen production, with therapeutic benefit.