Personalizing Second-Line Treatment Strategies in HR-Positive, HER2-Negative Advanced Breast Cancer

Dr. Jason Mouabbi and Dr. Seth Wander discuss considerations for treatment selection following first-line therapy in HR-positive, HER2-negative advanced breast cancer, highlighting the evolving definition of endocrine sensitivity and the growing role of precision medicine. Dr. Wander explains how the availability of newer endocrine-based therapies and targeted treatment approaches has expanded options for patients who experience disease progression. The discussion explores how molecular alterations, including ESR1 mutations, PIK3CA mutations, AKT pathway alterations, and other biomarkers, can influence treatment selection in the second-line setting. Dr. Wander also emphasizes ongoing challenges in patients without actionable alterations or those with multiple concurrent resistance mechanisms, highlighting the need for continued research to better guide sequencing strategies. The experts underscore the increasing complexity of treatment decisions as the field moves toward more individualized approaches for patients with HR-positive, HER2-negative advanced breast cancer.