Sex
steroids, particularly
estrogen and
progesterone, promote normal breast tissue growth and differentiation. Prolonged exposure of
estrogen and/or
progesterone is considered a risk factor for
breast cancer carcinogenesis, and the effects of sex
steroids on
breast cancer metastasis are controversial. Emerging evidence indicates that sex
steroids regulate
breast cancer metastatic processes via nongenomic and genomic mechanisms. Through the regulation of
actin-binding proteins estrogen and
progesterone rapidly provoke actin cytoskeleton reorganization in
breast cancer cells, leading to formation of membrane structures facilitating
breast cancer cell migration and invasion. In addition,
steroid receptors interact and trans-activate
receptor tyrosine kinases (including
epidermal growth factor receptor and
insulin-like growth factor receptor), resulting in
growth factor-like effects that promote
cancer cell invasive behavior. Moreover, sex
steroids regulate the expression of
metastasis-associated molecules, such as
E-cadherin,
matrix metalloproteinases,
growth factors,
chemokines and their receptors, leading to epithelial-to-mesenchymal-like transition. However, there is also evidence that sex
steroids and their receptors protect against
breast cancer cell invasiveness through distinct mechanisms. Here, we present an overview of the currently identified actions of sex
steroids on
breast cancer metastasis and their potential clinical implications.