Of course, these are not clear-cut divisions, considering that a change in the proportion of different cell types within a tumour (for example, cells that express hormone receptors in a mammary neoplasm) could lead to a breast cancer being reclassified as progressing from ER positive to ER negative disease i.e. a change in intra-tumour heterogeneity leads to a change in inter-tumour heterogeneity. Here, ESR1 is linked to breast cancer.