Supplementary Figure S1 from Comparison of Circulating Tumor DNA Assays for Molecular Residual Disease Detection in Early-Stage Triple-Negative Breast Cancer
posted on 2024-02-16, 09:40authored byMaria Coakley, Guillermo Villacampa, Prithika Sritharan, Claire Swift, Kathryn Dunne, Lucy Kilburn, Katie Goddard, Christodoulos Pipinikas, Patricia Rojas, Warren Emmett, Peter Hall, Catherine Harper-Wynne, Tamas Hickish, Iain Macpherson, Alicia Okines, Andrew Wardley, Duncan Wheatley, Simon Waters, Carlo Palmieri, Matthew Winter, Rosalind J. Cutts, Isaac Garcia-Murillas, Judith Bliss, Nicholas C. Turner
Correlation between the tumor fraction percentage as reported by mean Variant Allele Frequency (mean VAF) or estimated Variant Allele Frequency (eVAF) for the RaDaR ctDNA assay.
Funding
Cancer Research UK (CRUK)
NIHR Biomedical Research Centre, Royal Marsden NHS Foundation Trust/Institute of Cancer Research (BRC)
History
ARTICLE ABSTRACT
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.