e12606 Background: Circulating tumor (ct)DNA testing has emerged as a key prognostic biomarker for disease recurrence in breast cancer, with the potential to monitor treatment responses. Changes in ctDNA levels before and after neoadjuvant chemotherapy correlate with residual disease burden. This study investigates ctDNA molecular residual disease (MRD) monitoring in high-risk breast cancer patients. Methods: We conducted a retrospective chart review of electronic health records (EHR) from breast cancer patients at a Stanford satellite site between April 2023 and June 2025. Clinical and demographic data were extracted from the EHR. Tumor-informed ctDNA was assessed using the Signatera 16-plex mPCR-NGS assay. Inclusion criteria required a baseline ctDNA test prior to treatment and at least one follow-up assessment after 3–4 months of systemic treatment. Results: We identified 67 patients with matching ctDNA results, primarily non-Hispanic white (76%), followed by Hispanic (10%), non-Hispanic Black (8%), and Asian (6%). Six percent were male, and ten percent had confirmed germline mutations. Most patients had invasive ductal carcinoma, with some diagnosed with other histologies, including inflammatory breast cancer (6%). High-risk features, such as positive axillary lymph nodes and elevated genomic assay scores, were common. Of the cohort, 20 patients (30%) tested ctDNA-positive at one or more time points. Fourteen of these patients (70%) were ctDNA-positive before treatment. While 13 patients (93%) cleared ctDNA during therapy, one patient who was non-compliant developed oligo-brain metastasis despite clearance. In three patients (15%), ctDNA positivity during therapy prompted changes in management. In one case, rising ctDNA positivity in a stage IV patient led to re-imaging and identification of further disease progression. Two non-compliant patients resumed therapy—one with an aromatase inhibitor and the other with a CDK 4/6 inhibitor. Conclusions: In this real-world cohort, ctDNA testing was applied in various clinical contexts, including surveillance, treatment monitoring, and decision-making. Findings highlight substantial variability in ctDNA application in community practice and emphasize the need for prospective studies to define its clinical utility, optimal use cases, and impact on outcomes in ctDNA-guided breast cancer management. This study underscores the clinical implications of ctDNA monitoring and its potential to influence provider-patient discussions and improve treatment adherence.
Thompson et al. (Thu,) studied this question.