ESR1 and breast cancer: In breast cancer, clinically relevant alterations in PIK3CA, ESR1, BRCA2, and ERBB2 were among the most prevalent (Figs 5G & S4C); 46.8% (59/126) of HR+ HER2- breast cancer samples harbored either an ESR1 mutation predicting resistance to aromatase inhibitors [46], or a PIK3CA mutation predicting sensitivity to PI3K pathway inhibition by alpelisib [47], with 28.8% (17/59) of these samples harboring concurrent PIK3CA or ESR1 mutations (S5A Fig).