Looking Ahead: The Future of MRD Testing and Breast Cancer Management and Insights From ASCO 2025

The detection of ctDNA has revolutionized residual disease monitoring by offering sensitivity far beyond traditional imaging. When a patient has a positive ctDNA test at very low levels but normal scans and feels well, it poses a significant clinical challenge. This molecular signal often indicates microscopic disease that precedes visible recurrence by months or even years. Managing such cases requires integrating ctDNA results with the patient’s cancer subtype, treatment history, and overall clinical context. Rising ctDNA levels typically prompt closer surveillance and additional imaging to identify emerging metastases early, enabling timely intervention before symptoms develop.

Conversations with patients about low-level ctDNA positivity must balance hope with honesty. Patients often struggle to reconcile feeling healthy with a test that predicts likely recurrence. Physicians provide emotional support and explain that ctDNA is a highly sensitive biomarker—akin to a “molecular early warning system.” Although a positive test usually signals future disease progression, the lead time can vary, offering an opportunity to explore less-toxic, targeted therapies aimed at eradicating microscopic disease before it becomes clinically apparent. Shared decision-making is essential, as treatment decisions are individualized and consider the potential benefits, adverse effects, and patient preferences. This approach helps patients understand the rationale behind early intervention or continued monitoring despite negative imaging.

Looking ahead, ctDNA is poised to become an integral part of cancer staging and treatment planning, complementing traditional anatomic methods. Ongoing clinical trials aim to clarify the predictive value of ctDNA and evaluate novel therapies that may improve outcomes when started at the molecular residual disease stage. The future of oncology may include a “molecular metastatic” designation, guiding early, personalized treatment to prolong survival and maintain quality of life. This evolving paradigm holds great promise for transforming cancer care by detecting recurrence earlier and offering more effective, less-toxic interventions.