HR-Positive Breast Cancer: Evolving Role of ESR1 Mutations in Endocrine Resistance

This segment introduces the evolving treatment landscape in hormone receptor–positive, HER2-negative metastatic breast cancer, with a focus on the growing clinical relevance of ESR1 mutations. Dr. Adam Brufsky frames the discussion by highlighting the emerging paradigm of biomarker-driven decision-making, including the potential role of circulating tumor DNA in guiding therapy over time.

Dr. Hope S. Rugo reflects on how the understanding of ESR1 mutations has evolved from a largely observational biomarker to one that increasingly informs treatment selection. She discusses how ESR1 mutations arise under selective pressure from endocrine therapy, their dynamic and subclonal nature, and their implications for endocrine resistance. The conversation also explores how these insights are shaping the use of selective estrogen receptor degraders and combination strategies in clinical practice. Overall, this segment establishes a foundation for integrating molecular insights into treatment decision-making in HR-positive breast cancer.