Sex steroids and breast cancer metastasis

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.