ESR1 and neoplasm: ER signaling re-activation in the relapsed setting can occur due to changes in ligand sensitivity and specificity, for example, resistance to tamoxifen has been proposed to be a result of the selection of tumor cells that recognize the ER:tamoxifen complex as agonistic (Gottardis and Jordan, 1988; McDonnell and Wardell, 2010; Takimoto et al., 1999).