Taken together, these data demonstrate that selective inhibition of CREBBP/EP300 acetyltransferase activity blocks the proliferation of ER positive breast cancer cells in vitro and in vivo, and the enhanced efficacy in combination with Fulvestrant suggests that acetyltransferase inhibition has the potential to potentiate the effects of direct ER targeting, perhaps through increased engagement of ER transcriptional programs. Here, CREBBP is linked to breast carcinoma.