Although ER+ breast cancer is generally considered to have a relatively low frequency of p53 mutation, these do still occur in around 20% of cases in the primary and metastatic settings (29) and there is some evidence that the frequency of p53 mutation may be enriched in tumours resistant to CDK4/6i, with frequencies between 27% and 58% reported (17, 65, 66). This evidence concerns the gene ESR1 and breast carcinoma.