HER-2 loss in 21–50% and HER-2 gain in 30% of metastatic tumors [8,28], ER loss in 3.2–44% of metastatic tumors [29–31], and PR loss in 24% of metastatic tumors [31] have been reported, whereas no gain of ER or PR in metastatic tumors have been reported. This evidence concerns the gene ESR1 and metastatic neoplasm.