We do not find significant ligand-independent activity of this mutant in ER-negative cells in vitro, consistent with studies from an ESR1 E380Q patient-derived xenograft model15; however, our finding that the E380Q mutation occurred in two breast cancer patients' tissues and in one case at a high AF (18.1%), and further, one of these samples were collected before the administration of AI therapy suggest a functional role of this mutation in ER+ breast cancer independent of AI resistance. Here, ESR1 is linked to breast cancer.