SERENA-6 is a novel and exciting phase III clinical trial where patients with advanced ER+ HER2− breast cancer who are receiving an AI plus palbociclib or abemaciclib and have developed the ESR1 mutation but without overt disease progression will be randomized for a continuation of current treatment vs. switching AI to camizestrant with the continuation of the same CDK4/6 inhibitor [44]. The gene discussed is ESR1; the disease is breast cancer.