S17 Ep4: Show Me the Data: Translating Clinical and Practice-Based Evidence on Oral SERDs Into Everyday Care for HR+/HER2– Metastatic Breast Cancer

Managing HR-positive HER2-negative metastatic breast cancer requires precise, biomarker-driven treatment sequencing based on evolving clinical evidence. NGS testing at initial diagnosis is essential for identifying PIK3CA mutations, which inform future therapeutic choices and metabolic management. As ESR1 mutations frequently emerge following endocrine therapy and CDK4/6 inhibitor exposure, targeted Oral SERDs like elacestrant and imlunestrant offer significant progression-free survival benefits in these resistant populations. Emerging data indicate that combining these Oral SERDs with agents like everolimus or abemaciclib yields superior outcomes compared to monotherapy, even in patients with co-occurring PIK3CA and ESR1 alterations. While these combinations improve survival, they necessitate careful management of treatment-related toxicities, including hyperglycemia and gastrointestinal effects. Clinicians must balance these efficacy gains against the patient's prior treatment duration and the specific molecular profile of their disease to optimize long-term outcomes.