Current utilization of circulating tumor DNA (ctDNA) monitoring in patients with stage I-III breast cancer

Abstract While testing for circulating tumor DNA (ctDNA) in the surveillance setting of early-stage breast cancer is available and is currently being used nationwide, it is unknown how breast oncologists are utilizing ctDNA testing and whether testing patterns and/or results are currently impacting clinical care. To further understand this utilization, we identified 7,044 patients with stage I-III breast cancer who underwent personalized, tumor-informed ctDNA testing for molecular residual disease (MRD) in the postsurgical setting between 2019–2025. ctDNA results and clinicopathologic data were abstracted from available clinical records and insurance claims. For 5692/7044 patients with ≥ 2 ctDNA tests after definitive surgery, the median (range) time of initial testing was 7.87 (0.0-47.3) months after surgery; median interval between ctDNA tests was 3.4 (0.2–31.4) months. The negative predictive value (NPV) of a single negative ctDNA test was high for all tumor subtypes, with the highest NPVs (> 97%) observed within 12 months of the test. MRD detection within 3 months post-surgery was strongly associated with worse distant recurrence-free survival (DRFS; HR: 6.5, 95%CI: 4.1–10.3, p = 1.99e-13). ctDNA levels increased closer to the time of clinical recurrence and varied by tumor subtype; for patients with a positive ctDNA test within 3 months before clinical recurrence, the median (range) ctDNA concentration was 19.0 (0.03-14,248) and 4.41 (0.01-2,493) MTM/mL for triple-negative and estrogen receptor-positive HER2-negative breast cancers, respectively. In a subset analysis, positive ctDNA testing impacted clinical care for 36/44 (81.8%) patients with detectable ctDNA, leading to treatment changes in 7 patients, 4 of whom achieved ctDNA clearance following treatment change. These findings offer key insights into how personalized, tumor-informed ctDNA testing is being used in clinical practice as part of the management of care for patients with early breast cancer.