Comparison of circulating tumor DNA assays for Molecular Residual Disease detection in early-stage triple negative breast cancer

Coakley, M. et al. (2023) Comparison of circulating tumor DNA assays for Molecular Residual Disease detection in early-stage triple negative breast cancer. Clinical Cancer Research, (doi: 10.1158/1078-0432.CCR-23-2326) (Early Online Publication)

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 multi-mutation 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’s 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 timepoint was associated with a shorter time to relapse compared with detection at subsequent timepoints (median lead time 4.2 vs 7.1 months, p=0.02). Conclusions: Personalized multi-mutation sequencing assays have potential clinically important improvements in clinical outcome in the early detection of MRD.

• Item Type: Articles
• Additional Information: This work was supported in part by Le Cure, the Royal Marsden Cancer Charity. It was endorsed by Cancer Research UK (CRUKE/16/024) and the ICR Clinical Trials & Statistics Unit is supported by a core programme grant (grant number C1491/A15955) from Cancer Research UK. This study represents independent research funded by the National Institute for Health Research (NIHR) Biomedical Research Centre at The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, London.
• Status: Early Online Publication
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: MacPherson, Professor Iain
• Authors: Coakley, M., Villacampa, G., Sritharan, P., Swift, C., Dunne, K., Kilburn, L., Goddard, K., Pipinikas, C., Rojas, P., Emmett, W., Hall, P., Harper-Wynne, C., Hickish, T., MacPherson, I., Okines, A., Wardley, A., Wheatley, D., Waters, S., Palmieri, C., Winter, M., Cutts, R. J., Garcia-Murillas, I., Bliss, J., and Turner, N. C.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Clinical Cancer Research
• Publisher: American Association for Cancer Research
• ISSN: 1078-0432
• ISSN (Online): 1557-3265
• Published Online: 11 December 2023
• Copyright Holders: Copyright © 2023 by the American Association for Cancer Research
• First Published: First published in Clinical Cancer Research 2023
• Publisher Policy: Reproduced under a Creative Commons licence