Notably, preliminary results of the phase II BYLIEVE trial that investigated combined alpelisib and endocrine therapy (letrozole or fulvestrant) in patients with PIK3CA-mutated ER+ advanced breast cancer after progression on combined CDK4/6 inhibitor and endocrine therapy showed a longer PFS for patients previously treated with CDK4/6 inhibitor and an AI, which supported the clinical relevance of alpelisib in this subpopulation [38]. This evidence concerns the gene ESR1 and breast cancer.