Anti-hormonal agents that i) disrupt ER activity, such as tamoxifen, or ii) enzymatically block aromatase, such as letrozole or exemestane, or iii) selectively block and degrade ER, such as fulvestrant, are an essential part of current treatment strategies in adjuvant as well as advanced and metastatic disease [18]. This evidence concerns the gene ESR1 and metastatic neoplasm.