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

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Coakley, Maria ORCID: 0000-0003-2658-7789, Villacampa, Guillermo ORCID: 0000-0003-4868-6585, Sritharan, Prithika ORCID: 0009-0004-9733-3596, Swift, Claire ORCID: 0009-0003-6974-2926, Dunne, Kathryn ORCID: 0009-0007-7259-744X, Kilburn, Lucy ORCID: 0000-0002-1987-7545, Goddard, Katie ORCID: 0009-0006-6682-4418, Pipinikas, Christodoulos ORCID: 0009-0007-7310-167X, Rojas, Patricia ORCID: 0000-0003-4298-731X, Emmett, Warren ORCID: 0009-0002-4739-1515 et al (show 14 more authors) , Hall, Peter ORCID: 0000-0001-6015-7841, Harper-Wynne, Catherine ORCID: 0000-0002-8414-6722, Hickish, Tamas ORCID: 0000-0001-6770-7279, Macpherson, Iain ORCID: 0000-0003-4295-8885, Okines, Alicia ORCID: 0000-0002-2068-2593, Wardley, Andrew ORCID: 0000-0002-9639-0888, Wheatley, Duncan ORCID: 0000-0002-1919-5114, Waters, Simon ORCID: 0000-0003-0205-4398, Palmieri, Carlo ORCID: 0000-0001-9496-2718, Winter, Matthew ORCID: 0000-0001-6192-9874, Cutts, Rosalind J ORCID: 0000-0002-8297-9341, Garcia-Murillas, Isaac ORCID: 0000-0001-8183-7969, Bliss, Judith ORCID: 0000-0001-7957-7424 and Turner, Nicholas C ORCID: 0000-0001-8937-0873 (2024) Comparison of Circulating Tumor DNA Assays for Molecular Residual Disease Detection in Early-Stage Triple-Negative Breast Cancer. Clinical cancer research : an official journal of the American Association for Cancer Research, 30 (4). pp. 895-903.

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Abstract

<h4>Purpose</h4>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.<h4>Experimental design</h4>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.<h4>Results</h4>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).<h4>Conclusions</h4>Personalized multimutation sequencing assays have potential clinically important improvements in clinical outcome in the early detection of MRD.

Item Type:	Article
Uncontrolled Keywords:	Humans, Neoplasm Recurrence, Local, Neoplasm, Residual, Recurrence, Triple Negative Breast Neoplasms, Biomarkers, Tumor, Circulating Tumor DNA
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User:	Symplectic Admin
Date Deposited:	06 Mar 2024 10:31
Last Modified:	02 Apr 2024 09:31
DOI:	10.1158/1078-0432.ccr-23-2326
Open Access URL:	https://doi.org/10.1158/1078-0432.CCR-23-2326
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3179164