Comparison of Circulating Tumor DNA Assays for Molecular Residual Disease Detection in Early-Stage Triple-Negative Breast Cancer

• Published in: Clinical cancer research 2024-02, Vol.30 (4), p.895-903
• Main Authors: Coakley, Maria, Villacampa, Guillermo, Sritharan, Prithika, Swift, Claire, Dunne, Kathryn, Kilburn, Lucy, Goddard, Katie, Pipinikas, Christodoulos, Rojas, Patricia, Emmett, Warren, Hall, Peter, Harper-Wynne, Catherine, Hickish, Tamas, Macpherson, Iain, Okines, Alicia, Wardley, Andrew, Wheatley, Duncan, Waters, Simon, Palmieri, Carlo, Winter, Matthew, Cutts, Rosalind J, Garcia-Murillas, Isaac, Bliss, Judith, Turner, Nicholas C
• Format: Article
• Language: English
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-23-2326

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. 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. 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). Personalized multimutation sequencing assays have potential clinically important improvements in clinical outcome in the early detection of MRD.