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ASCO 2025: Optimizing Breast Cancer Surveillance With ctDNA Testing: Transforming Early Detection and Recurrence Monitoring - Episode 5

Monitoring Response in Real Time: ctDNA as a Predictive and Surrogate Marker in Early Treatment

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Panelists discuss how circulating tumor DNA (ctDNA) is becoming a vital biomarker in breast cancer, with its dynamic changes guiding personalized treatment decisions, serving as a surrogate end point in trials, enabling earlier detection of progression, and offering a less-invasive monitoring tool that complements imaging—especially benefiting patients with hard-to-monitor disease or those who are frail.

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The dynamic nature of ctDNA has emerged as a powerful tool in both clinical trial design and real-world oncology practice, particularly in breast cancer. One of the most promising aspects of ctDNA is its potential as an early and actionable biomarker. Evidence shows that patients with higher initial ctDNA levels tend to have worse outcomes, whereas those who clear ctDNA early in treatment are more likely to achieve a pathological complete response and have improved long-term prognosis. These insights make ctDNA clearance an attractive surrogate end point for trials evaluating treatment efficacy and de-escalation strategies.

Incorporating ctDNA into clinical trial frameworks offers opportunities to personalize therapy. For instance, patients who clear ctDNA early during neoadjuvant therapy may not require additional toxic agents, such as anthracyclines, potentially reducing long-term adverse effects. Conversely, patients whose ctDNA levels rise or fail to clear could benefit from therapeutic escalation or novel targeted interventions. Frequent monitoring, particularly in the metastatic setting, allows clinicians to detect disease progression earlier than imaging or symptoms would typically permit. This is especially relevant in difficult-to-monitor subtypes, such as invasive lobular carcinoma or bone-only disease, where traditional imaging may be less reliable.

In clinical practice, ctDNA has found utility beyond high-risk patients. For older or frail individuals, ctDNA monitoring offers a less burdensome alternative to frequent imaging. Baseline testing is essential, not only to validate disease detection but also to set the foundation for dynamic monitoring. Although not yet a stand-alone replacement for imaging, ctDNA serves as a valuable complement, particularly for assessing treatment response and detecting resistance mutations. The evolving evidence supports a broader integration of ctDNA into routine care, especially as assay accessibility and reimbursement continue to improve.

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