After exposure to nonsteroidal AIs for metastatic disease, 29–39% [11,12,13] of patients harbor ESR1 mutations, whereas ESR1 mutations are quite rare in primary tumors (only ~3% of patients [14,15]) and newly diagnosed metastatic disease after adjuvant treatment with AIs (5.3–6.4% of patients [16,17,18]). Here, ESR1 is linked to metastatic neoplasm.