The lower steroid response (including lower ESR1 expression) in HER2E tumors may serve as a possible explanation for the poor response to endocrine therapy and are consistent with a hypothesis that acquisition of the HER2E subtype in metastatic disease is linked to estrogen independence16, further supporting chemotherapy as part of early management for patients with HER2E tumors. Here, ESR1 is linked to metastatic neoplasm.