Intracellular responses of ER-positive breast cancers to selective estrogen receptor modulators (SERMs) like tamoxifen are dependent on two different ER-regulated gene mechanisms: one in which liganded ER binds promoter DNA at an estrogen responsive element (ERE), and another in which ER becomes tethered to other promoter-bound transcription factors [1,2]. The gene discussed is ESR1; the disease is breast carcinoma.