Here we show, for the first time, that BD and 4-OHT/TAM work synergistically against breast cancer by suppressing estradiol-induced proliferation of MCF-7 cells in vitro and tumor growth in vivo, which related to induced apoptosis and regulation of TAM resistant proteins (p21/CDKN1A and Bcl-2) expression. Here, CDKN1A is linked to breast cancer.