ESR1 and breast cancer: PI3Kα-selective inhibitors are now making good progress in the clinic [4], with the PI3Kα-specific inhibitor alpelisib (Piqray/NVP-BYL719; Novartis) receiving approval for the treatment of advanced hormone-receptor (HR)-positive, HER2-negative breast cancers, in combination with the estrogen receptor (ER) antagonist fulvestrant [5].