Personalized detection of circulating tumor DNA antedates breast cancer metastatic recurrence
Authors
Coombes, RPage, K
Salari, R
Hastings, R
Armstrong, Anne C
Ahmed, S
Ali, S
Cleator, S
Kenny, L
Stebbing, J
Rutherford, M
Sethi, H
Boydell, A
Swenerton, R
Fernandez-Garcia, D
Gleason, K
Goddard, K
Guttery, D
Assaf, Z
Wu, H
Natarajan, P
Moore, D
Primrose, L
Dashner, S
Tin, A
Balcioglu, M
Srinivasa, R
Shchegrova, S
Olson, A
Hafez, D
Billings, P
Aleshin, A
Rehman, F
Toghill, B
Hills, A
Louie, M
Lin, C
Zimmermann, B
Shaw, J
Affiliation
Surgery and Cancer, Imperial College LondonIssue Date
2019
Metadata
Show full item recordAbstract
PURPOSE: Up to 30% of breast cancer patients relapse after primary treatment. There are no sensitive and reliable tests to monitor these patients and detect distant metastases before overt recurrence. Here we demonstrate the use of personalized ctDNA profiling for detection of recurrence in breast cancer. METHODS: Forty-nine primary breast cancer patients were recruited following surgery and adjuvant therapy. Plasma samples (n=208) were collected every 6 months for up to 4 years. Personalized assays targeting 16 variants selected from primary tumor whole exome data were tested in serial plasma for the presence of ctDNA by ultra-deep sequencing (average >100,000X). RESULTS: Plasma ctDNA was detected ahead of clinical or radiological relapse in 16 of the 18 relapsed patients (sensitivity of 89%); metastatic relapse was predicted with a lead time of up to 2 years (median=8.9 months; range: 0.5-24.0 months). None of the 31 non-relapsing patients were ctDNA-positive at any time point across 156 plasma samples (specificity of 100%). Of the two relapsed patients who were not detected in the study, the first had only a local recurrence, while the second patient had bone recurrence and had completed chemotherapy just 13 days prior to blood sampling. CONCLUSIONS: This study demonstrates that patient-specific ctDNA analysis can be a sensitive and specific approach for disease surveillance for breast cancer patients. More importantly, earlier detection of up to two years provides a possible window for therapeutic intervention.Citation
Coombes RC, Page K, Salari R, Hastings RK, Armstrong AC, Ahmed S, et al. Personalized detection of circulating tumor DNA antedates breast cancer metastatic recurrence. Clin Cancer Res. 2019.Journal
Clinical Cancer ResearchDOI
10.1158/1078-0432.CCR-18-3663PubMed ID
30992300Additional Links
https://dx.doi.org/10.1158/1078-0432.CCR-18-3663Type
ArticleLanguage
enae974a485f413a2113503eed53cd6c53
10.1158/1078-0432.CCR-18-3663
Scopus Count
Collections
Related articles
- Assessment of Molecular Relapse Detection in Early-Stage Breast Cancer.
- Authors: Garcia-Murillas I, Chopra N, Comino-Méndez I, Beaney M, Tovey H, Cutts RJ, Swift C, Kriplani D, Afentakis M, Hrebien S, Walsh-Crestani G, Barry P, Johnston SRD, Ring A, Bliss J, Russell S, Evans A, Skene A, Wheatley D, Dowsett M, Smith IE, Turner NC
- Issue date: 2019 Oct 1
- Identification of minimal residual disease using the clonesight test for ultrasensitive ctDNA detection to anticipate late relapse in early breast cancer.
- Authors: Comino-Méndez I, Velasco-Suelto J, Pascual J, López-López E, Quirós-Ortega ME, Gaona-Romero C, Martín-Muñoz A, Losana P, Heredia Y, Alba E, Guerrero-Zotano A
- Issue date: 2025 May 1
- Longitudinal monitoring of circulating tumor DNA to detect relapse early and predict outcome in early breast cancer.
- Authors: Garcia-Murillas I, Cutts RJ, Walsh-Crestani G, Phillips E, Hrebien S, Dunne K, Sidhu K, Daber R, Hubert B, Graybill C, DeFord PM, Wooten DJ, Zhao J, Ellsworth RE, Johnston SRD, Ring A, Russell S, Evans A, Skene A, Wheatley D, Smith IE, Korn WM, Turner NC
- Issue date: 2025 Feb
- Whole genome sequencing-powered ctDNA sequencing for breast cancer detection.
- Authors: Garcia-Murillas I, Abbott CW, Cutts RJ, Boyle SM, Pugh J, Keough KC, Li B, Pyke RM, Navarro FCP, Chen RO, Dunne K, Bunce C, Johnston SRD, Ring A, Russell S, Evans A, Skene A, Smith IE, Turner NC
- Issue date: 2025 Jun
- Serial Postoperative Circulating Tumor DNA Assessment Has Strong Prognostic Value During Long-Term Follow-Up in Patients With Breast Cancer.
- Authors: Shaw JA, Page K, Wren E, de Bruin EC, Kalashnikova E, Hastings R, McEwen R, Zhang E, Wadsley M, Acheampong E, Renner D, Gleason KLT, Ambasager B, Stetson D, Fernandez-Garcia D, Guttery D, Allsopp RC, Rodriguez A, Zimmermann B, Sethi H, Aleshin A, Liu MC, Richards C, Stebbing J, Ali S, Rehman F, Cleator S, Kenny L, Ahmed S, Armstrong AC, Coombes RC
- Issue date: 2024 Apr