For example, the spatial heterogeneity of immune cells, stromal cells and epithelial cancer cells assessed by haematoxylin and eosin routine histopathology sections has been shown to be associated with a poor response to standard therapies in both ER + and ER- primary breast cancers, suggesting that having a mixture of these cells within the tumour microenvironment allows adaptation as the cancer evolves102. This evidence concerns the gene ESR1 and breast cancer.