Comparison of Circulating Tumor DNA Assays for Molecular Residual Disease Detection in Early-Stage Triple-Negative Breast Cancer
Maria Coakley, Guillermo Villacampa, Prithika Sritharan, Claire Swift, Kathryn Dunne, Lucy Kilburn, Katie Goddard, Christodoulos Pipinikas, Patricia Rojas, Warren Emmett, Peter S Hall, Catherine Harper‐Wynne, Tamas Hickish, Iain R. Macpherson, Alicia Okines, Andrew Wardley, Duncan Wheatley, Simon Waters, Carlo Palmieri, Matthew Winter, Rosalind Cutts, Isaac García-Murillas, Judith M. Bliss, Nicholas C. Turner
Abstract
PURPOSE: Detection of circulating tumor DNA (ctDNA) in patients who have completed treatment for early-stage breast cancer is associated with a high risk of relapse, yet the optimal assay for ctDNA detection is unknown. EXPERIMENTAL DESIGN: The cTRAK-TN clinical trial prospectively used tumor-informed digital PCR (dPCR) assays for ctDNA molecular residual disease (MRD) detection in early-stage triple-negative breast cancer. We compared tumor-informed dPCR assays with tumor-informed personalized multimutation sequencing assays in 141 patients from cTRAK-TN. RESULTS: MRD was first detected by personalized sequencing in 47.9% of patients, 0% first detected by dPCR, and 52.1% with both assays simultaneously (P < 0.001; Fisher exact test). The median lead time from ctDNA detection to relapse was 6.1 months with personalized sequencing and 3.9 months with dPCR (P = 0.004, mixed-effects Cox model). Detection of MRD at the first time point was associated with a shorter time to relapse compared with detection at subsequent time points (median lead time 4.2 vs. 7.1 months; P = 0.02). CONCLUSIONS: Personalized multimutation sequencing assays have potential clinically important improvements in clinical outcome in the early detection of MRD.