Although further studies are essential to show that inhibitors of mitogenic signaling can restore ER expression and/or function in breast tumors, coupling molecules such as signal transduction inhibitors, monoclonal antibodies, demethylating agents or NF-κB inhibitors with antiestrogens could result in therapies that are better tolerated and active for the treatment of ER-negative breast cancer. This evidence concerns the gene NFKB1 and breast neoplasm.