Newly detected alterations at EOT were predominantly observed in genes associated with the ER, PI3K and p53 signalling pathways (Fig. 6A–C and Fig. S7C), suggesting that the activation or dysregulation of these signalling pathways contributes to clinical resistance to PI3K inhibition plus ET in ER+, HER2− breast tumours. This evidence concerns the gene ESR1 and breast neoplasm.