ESR1 and breast carcinoma: Here we demonstrate that abrogation of ER signaling with tamoxifen, fulvestrant, or AZD9496 results in radiosensitization of ER+ breast cancer cell lines (Fig. 1 and Supplementary Figs. 1 and 2) through the inhibition of DNA damage repair via NHEJ (Fig. 2) and an induction of cellular senescence with combination treatment of ET and RT (Fig. 4).