ESR1 and neoplasm: Changes in tumour phenotype or in the intrinsic molecular subtype during progression occurs in around 30% of patients (most often involving the down regulation of PR, but may also involve ER and less frequently a change in HER2 status) and may occur in a non-random manner at specific metastatic sites (e.g., lung, liver and bone metastases) [85,86,87,88].