Managing ESR1-Mutated HR-Positive, HER2-Negative Advanced Breast Cancer After Disease Progression

Dr. Jason Mouabbi and Dr. Seth Wander discuss treatment considerations for patients with HR-positive, HER2-negative advanced breast cancer who develop ESR1 mutations following first-line endocrine therapy and CDK4/6 inhibition. Dr. Wander reviews how ESR1 mutation status has emerged as an important biomarker for guiding treatment selection after disease progression and discusses clinical evidence supporting the use of next-generation endocrine therapies in this setting. The conversation highlights findings from studies such as EMERALD and other emerging data evaluating endocrine-based approaches for ESR1-mutated disease. Dr. Wander also discusses factors that may influence treatment decisions, including duration of benefit from prior CDK4/6 inhibitor therapy, ongoing endocrine sensitivity, and the presence of additional molecular alterations. The experts emphasize the importance of individualized treatment selection and continued research to refine sequencing strategies for patients with HR-positive, HER2-negative advanced breast cancer.