ASCO 2025: Optimizing Breast Cancer Surveillance With ctDNA Testing: Transforming Early Detection and Recurrence Monitoring - Episode 8
Applying ctDNA Insights to Real-World Decisions and Tumor Evolution
Panelists discuss the real-world challenges of managing patients with positive circulating tumor DNA (ctDNA) but no radiographic evidence of disease, emphasizing treatment intensification, genomic profiling for resistance mutations, dynamic monitoring, and the integration of ctDNA with imaging and biopsy to guide personalized breast cancer care.
While awaiting results from ongoing trials to better guide therapy, clinicians face real-time challenges when patients present with positive ctDNA but show no radiographic evidence of disease. Doing nothing is generally considered unacceptable, given the strong prognostic implications of ctDNA positivity. Treatment decisions often involve switching or intensifying endocrine therapies; for example, moving from tamoxifen to aromatase inhibitors or adding ovarian suppression in premenopausal women. For eligible patients, CDK4/6 inhibitors are frequently underutilized, though they can be introduced even after initial adjuvant treatment has concluded, sometimes with success in converting ctDNA positivity to negativity and delaying recurrence.
In clinical practice, ctDNA is used not only as a prognostic marker but also as a tool to tailor treatments more precisely. When ctDNA is detected, comprehensive genomic profiling is often employed to identify resistance mutations such as ESR1, which may guide the early use of targeted therapies such as selective estrogen receptor degraders or CDK4/6 inhibitors. This approach allows for more dynamic monitoring of treatment response and helps adjust therapy in real time rather than relying solely on imaging at fixed intervals. Ongoing clinical trials are increasingly incorporating ctDNA measurements to evaluate their potential in guiding personalized treatment decisions in both the adjuvant and metastatic settings.
When radiographic abnormalities accompany positive ctDNA findings, confirmatory biopsy remains the standard to ensure accurate diagnosis before initiating treatment, distinguishing true metastatic disease from benign lesions. The combination of quantitative ctDNA analysis and genomic sequencing complements imaging studies and biopsy, providing a more complete picture of disease status. Together, these tools enable more informed, patient-specific management strategies in the evolving landscape of cancer care.
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