ASCO 2025: Optimizing Breast Cancer Surveillance With ctDNA Testing: Transforming Early Detection and Recurrence Monitoring - Episode 4
Personalizing Early Breast Cancer Care: ctDNA Surveillance Insights From E-BLIS and I-SPY 2
Panelists discuss how emerging data from studies like E-BLIS and I-SPY 2 validate circulating tumor DNA (ctDNA) as a powerful prognostic tool in early breast cancer, showing it can detect recurrence months before imaging and potentially refine risk stratification beyond traditional markers, though its role in guiding treatment decisions remains under active investigation.
The evolving data from pivotal studies like the E-BLIS and I-SPY2 trials reinforce the prognostic strength of ctDNA in early breast cancer. The E-BLIS study followed patients over more than a decade and demonstrated that ctDNA monitoring could detect recurrence well in advance of clinical or radiographic evidence—often with a median lead time of nearly 10 months. The sensitivity of ctDNA in this context, detecting 30 of 34 recurrences, underscores its value in identifying patients at high risk for relapse, particularly those with hormone receptor–positive tumors, where the lead time is longest. These findings support the idea of tailored surveillance strategies based on tumor subtype.
The I-SPY 2 trial added another critical dimension by showing that ctDNA not only predicts recurrence but also serves as an independent prognostic factor beyond traditional markers, such as pathological complete response. This suggests that ctDNA can complement and possibly enhance our existing framework for risk stratification. Importantly, baseline ctDNA detection was more predictive of distant recurrence-free survival than any individual clinicopathologic feature. These insights raise the question of whether persistent molecular residual disease, detected by ctDNA, should prompt similar therapeutic intensification as residual disease seen on tissue after neoadjuvant therapy.
Although the evidence strongly supports the prognostic role of ctDNA, its predictive value remains under investigation. Clinicians are not yet using ctDNA negativity to withhold chemotherapy, but its use in guiding escalation or de-escalation strategies is a growing area of research. Serial ctDNA monitoring, rather than isolated time points, may better inform treatment efficacy and recurrence risk. The ability to assess ctDNA dynamics—clearance, persistence, or trend—offers clinicians a more refined tool to personalize surveillance and therapy, ultimately improving patient outcomes.
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