The faculty open the episode by discussing how most patients with hormone receptor-positive, HER2-negative metastatic breast cancer begin treatment with a CDK4/6 inhibitor plus an aromatase inhibitor and many respond well, sometimes for years. However, the aromatase inhibitor also creates selective pressure that can drive ESR1 mutation emergence and clonal expansion over time. The panel delves into a deep discussion of these complex biological processes of clonal evolution and development of resistance mechanisms, explaining how these changes affect first-line and subsequent line treatment selection and how they shape discussions with patients, noting the value of laying groundwork for patient understanding so that conversations surrounding resistance mechanisms are anticipated rather than alarming.
