The pivotal SOLAR-1 trial demonstrated that the addition of PIK3CA inhibitor Alpelisib to the selective ER degrader Fulvestrant significantly prolonged progression-free survival (PFS) in ER+Her2− BC and established this biological-hormonal combination in this subset of biomarker-positive patients.3 Later, the combination of the AKT-inhibitor capivasertib and fulvestrant was shown to improve progression-free survival in ER+her2− metastatic BC relative to fulvestrant alone in patients with AKT pathway-altered (PIK3CA, AKT1, or PTEN) tumors.4 The gene discussed is ESR1; the disease is breast cancer.