HR-Positive Breast Cancer: ctDNA-Guided De-escalation and Clinical Uncertainty

This segment explores the emerging and controversial role of circulating tumor DNA in guiding treatment decisions in hormone receptor–positive, HER2-negative metastatic breast cancer. Dr. Adam Brufsky raises the question of whether ctDNA can be used to detect progression earlier than imaging or even guide treatment de-escalation in patients with sustained disease control.

Dr. Hope S. Rugo emphasizes that there are currently no data to support stopping therapy based on negative ctDNA results and cautions against extrapolating beyond available evidence. She highlights that existing studies evaluating recurrence risk have been conducted in patients receiving standard therapy, not in those who discontinue treatment.

Dr. Mabel Mardones adds that while patients are increasingly requesting ctDNA-guided decisions, clinicians must carefully communicate the risks of disease progression and uncertainty. The discussion also highlights growing real-world use despite limited evidence. Overall, this segment underscores the tension between innovation, patient demand, and evidence-based care.