Utility of urinary ctDNA to monitoring minimal residual disease in early breast cancer patients.

Abstract

Cancer recurrence for patients with early breast cancer is significant. Patients will benefit from more non-invasive modes of monitoring and we aim to study the feasibility of urinary circulating tumor DNA (ctDNA) to monitor for residual disease (MRD). In this longitudinal study, 300 early breast cancer patients were recruited prospectively. Measurements were taken prior to treatment and at different time points thereafter for a total of 8 measurements. Comparisons were made with healthy volunteers and patients without detectable mutations in urine specimens. Disease free relapse were correlated to both urinary DNA quantity and ctDNA concentration. Baseline index measurements showed 38% of patients with detectable mutations. The concordance with biopsy tissues was 97.3%. Overall, breast cancer patients had higher urinary DNA compared with healthy volunteers. Over time, fluctuations in urinary DNA was negligible in healthy volunteers, indicating the stability of the marker. Among the patients with detectable mutations, we observed that higher urinary DNA quantity measurements at 6-month and patients with positive mutations were associated with greater risk of relapse. Hazard ratios for patients in this category was 1.65 (95% CI 1.26-2.16) and 1.98 (95% CI 1.48-2.63) respectively. Urinary DNA offers non-invasive probing and real-time monitoring of breast cancer relapse. Our results demonstrated clear clinical relevance in breast cancer and significant risk profiling of early breast cancer patients. This potentially aids to complement current cancer relapse monitoring and may help in early intervention.