A recent clinical sequencing study in patients with advanced ER+ breast cancer has identified a D538G mutation within ER in patients resistant to endocrine therapy, causing a change from aspartic acid to glycine at position 538 within the ligand binding domain.18 Similar to the D538G mutation, ER has been found to confer constitutive ligand‐independent transcriptional activity that mimicked that of estrogen‐bound wild‐type ER with reduced tamoxifen‐binding affinity. Here, ESR1 is linked to breast carcinoma.