HR and breast cancer: In HR + /HER2- BC, ESR1 alterations overall and ESR1 missense mutations were more frequent in samples from metastatic compared to local/regional sites (overall: n = 86/321 (26.8%) and n = 53/1427 (3.7%), respectively (P < 0.001); missense: n = 72/321 (22.4%) and n = 20/1427 (1.4%), respectively (P < 0.001)).