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). This evidence concerns the gene ESR1 and breast cancer.