SERENA-6 (ClinicalTrials.gov identifier: NCT04964934) is another ongoing phase 3 trial that evaluates the efficacy and safety of substituting from an aromatase inhibitor to camizestrant, but continuing the same CDK4/6 inhibitors, upon finding of ESR1 mutations in circulating tumor DNA before progression of the disease on first-line therapy for HR+/HER2− advanced breast cancer [117]. Here, CDK4 is linked to breast cancer.