The phase II BYLieve trial is the first prospective study to evaluate alpelisib plus endocrine therapy (fulvestrant or letrozole) in patients with HR-positive, HER2-negative, PIK3CA-mutated advanced breast cancer who have progressed on or after prior treatment with a CDK4/6 inhibitor.1–5 Patients enrolled in BYLieve (N = 336) were assigned to study cohorts (A-C) based on their most immediate prior treatment history (Table 1). The gene discussed is CDK4; the disease is breast cancer.