Evaluating Early Intervention Strategies in ESR1-Mutated HR-Positive, HER2-Negative Advanced Breast Cancer

Dr. Jason Mouabbi and Dr. Seth Wander discuss the clinical rationale for identifying and addressing ESR1-mediated endocrine resistance earlier in patients with HR-positive, HER2-negative advanced breast cancer. Dr. Wander reviews the PADA-1 study and its role in evaluating whether serial monitoring for emerging ESR1 mutations could guide endocrine therapy modification before clinical or radiographic progression. The experts discuss the strategy of maintaining CDK4/6 inhibition while changing the endocrine therapy backbone after ESR1 mutation detection and highlight how this approach has informed ongoing investigation into biomarker-guided treatment adaptation. Dr. Mouabbi and Dr. Wander also discuss how evolving endocrine therapies may address mechanisms of resistance and support more individualized treatment strategies. The conversation emphasizes the growing importance of understanding tumor evolution and optimizing the timing of therapeutic interventions in HR-positive, HER2-negative advanced breast cancer.