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

Thumbnail Image

Files

Comparison of Circulating Tumor DNA Assays for Molecular Residual Disease Detection in Early-Stage Triple-Negative Breast Ca.pdf (1.93 MB)

Embargo End Date

ICR Authors

Coakley, Maria
 Kilburn, Lucy
 Cutts, Rosalind
 Garcia-Murillas, Isaac
 Bliss, Judith
 Turner, Nicholas

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, RJ
Garcia-Murillas, I
Bliss, J
Turner, NC

Document Type

Journal Article

Date

2024-02-16

Date Accepted

2023-12-06

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.

Citation

Clinical Cancer Research, 2024, 30 (4), pp. 895 - 903

DOI

10.1158/1078-0432.CCR-23-2326
10.1158/1078-0432.CCR-23-2326

URI

https://repository.icr.ac.uk/handle/internal/6178

Rights

http://creativecommons.org/licenses/by/4.0/

Source Title

Clinical Cancer Research

Publisher

AMER ASSOC CANCER RESEARCH

ISSN

1078-0432

eISSN

1557-3265
1557-3265

Collections

Breast Cancer Research

Research Team

Molecular Oncology
Clin Trials & Stats Unit

Notes