Serena-6 (NCT04964934) is a phase III, double-blind, randomized trial that could assess switching to AZD9833 (a next-generation oral SERD) plus CDK4/6is (palbociclib or abemaciclib) vs. continuing AI (letrozole or anastrozole) plus CDK4/6is in HR+/HER2− metastatic BC patients with detectable ESR1 mutation without disease progression during first-line treatment with IA plus CDK4/6is (recruiting). The gene discussed is CDK4; the disease is breast cancer.