ESR1 and neoplasm: However, subclonal divergence of metastases is invariably observed within patients: driver and non-driver gene mutations are heterogeneously accumulated in different metastases, subsets of metastases may therefore be more closely related to each other than they are to other metastases, and heterogenous tumour phenotypes (ER positive and ER negative) often coincide with this divergent history [75,84,90].