Clinical Scenarios and Biomarker-Driven Treatment Selection in HR+/HER2− mBC

The panel applies the treatment framework to clinical scenarios involving patients with hormone receptor-positive, HER2-negative metastatic breast cancer (HR+/HER2− mBC) after progression on first-line CDK4/6 inhibitor plus endocrine therapy. Dr. Erica Mayer first considers a patient with no actionable ESR1 or PI3K pathway alteration, outlining options that include switching CDK4/6 inhibitors with fulvestrant, everolimus-based endocrine therapy, and gedatolisib-based treatment. She emphasizes that selection should incorporate prior CDK4/6 inhibitor sensitivity and tolerability, disease burden and pace, symptoms, quality-of-life priorities, and the practical burden of oral versus intravenous treatment. The case is then modified to include an ESR1 Y537S mutation, shifting the discussion toward novel endocrine therapies, with combination strategies generally preferred when available. Finally, a patient with a pathogenic PIK3CA H1047R mutation and no ESR1 alteration is considered, with capivasertib plus fulvestrant presented as a current option and gedatolisib-based therapy identified as an anticipated approach pending appropriate access. The segment concludes by reinforcing biomarker-driven treatment selection and multidisciplinary management in HR+/HER2− mBC.