Several clinical trials and studies highlighted the bidirectional cross‐talk between HER2 and ER when both receptors are expressed in BC cells [54, 56, 57, 58, 59, 60, 61, 62], and these reports concluded that HER2‐positive tumours differ in main clinicopathological features and natural history of disease depending on HR expression. This evidence concerns the gene ESR1 and breast cancer.