Why are estrogen-receptor-negative breast cancers more aggressive than the estrogen-receptor-positive breast cancers?

It is well established that some of the hormone-resistant breast cancers lack functional estrogen receptor (ER) and exhibit a more aggressive metastatic phenotype. The estrogen activation of ER in ER-positive breast cancers enhances their aggressiveness, while the activation of exogenously introduced ERs into aggressive ER-negative cells diminishes their aggressiveness. The basis of the protective effect of the ER appears complex and could be due to the altered expression of genes involved in cell proliferation, differentiation and invasiveness. In this review, we propose different mechanisms for the higher aggressiveness of most of the ER-negative breast cancers.