ESR1 and breast cancer: Alpelisib (BYL719), an oral inhibitor targeting PI3Kα developed by Novartis, was approved by the FDA for ER+/HER2-advanced metastatic breast cancer treatment in 2019.993 Inavolisib (GDC-0077) is also an oral inhibitor targeting PI3Kα with multiple ongoing clinical trials,997 including a phase III clinical trial (NCT05646862) for the treatment of HR+, HER2−, PIK3CA mutated breast cancer, and a phase II clinical trial (NCT05306041) for HR+, HER2+, PIK3CA mutated breast cancer.