Exploring Biomarker-Guided Treatment Adaptation in HR-Positive, HER2-Negative Advanced Breast Cancer

Dr. Jason Mouabbi and Dr. Seth Wander discuss emerging evidence evaluating proactive treatment strategies for patients with HR-positive, HER2-negative advanced breast cancer with ESR1 mutations. Building on concepts established by the PADA-1 study, the experts review the rationale behind monitoring for ESR1 mutations during treatment and adapting therapy before radiographic disease progression. Dr. Wander explains how ESR1-mutant tumor populations may evolve under continued treatment pressure, potentially leading to additional resistance mechanisms over time. The discussion highlights findings from the SERENA-6 trial, including the strategy of switching the endocrine therapy backbone while maintaining CDK4/6 inhibition following ESR1 mutation detection. Dr. Mouabbi and Dr. Wander emphasize the importance of understanding tumor evolution, timing of intervention, and how biomarker-guided approaches may influence future treatment strategies for patients with HR-positive, HER2-negative advanced breast cancer.