ESR1 and metastatic neoplasm: Since the loss of ER and/or PgR expression in recurrent HR+ disease may arise from clonal selection of biologically heterogeneous primary or metastatic tumor cell populations under the selective pressure of reduced extracellular estrogen levels or pharmacologic inhibition of the ER pathway, repeating FES PET/CT scans during the course of ET may help guide therapeutic decision making [21,22,23,24].