Personalized detection of circulating tumor DNA antedates breast cancer metastatic recurrence
Armstrong, Anne C
AffiliationSurgery and Cancer, Imperial College London
MetadataShow full item record
AbstractPURPOSE: 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.
CitationCoombes 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.
JournalClinical Cancer Research
- 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
- Ultradeep targeted sequencing of circulating tumor DNA in plasma of early and advanced breast cancer.
- Authors: Chin YM, Takahashi Y, Chan HT, Otaki M, Fujishima M, Shibayama T, Miki Y, Ueno T, Nakamura Y, Low SK
- Issue date: 2021 Jan
- Targeted next-generation sequencing of circulating-tumor DNA for tracking minimal residual disease in localized colon cancer.
- Authors: Tarazona N, Gimeno-Valiente F, Gambardella V, Zuñiga S, Rentero-Garrido P, Huerta M, Roselló S, Martinez-Ciarpaglini C, Carbonell-Asins JA, Carrasco F, Ferrer-Martínez A, Bruixola G, Fleitas T, Martín J, Tébar-Martínez R, Moro D, Castillo J, Espí A, Roda D, Cervantes A
- Issue date: 2019 Nov 1
- Prediction and monitoring of relapse in stage III melanoma using circulating tumor DNA.
- Authors: Tan L, Sandhu S, Lee RJ, Li J, Callahan J, Ftouni S, Dhomen N, Middlehurst P, Wallace A, Raleigh J, Hatzimihalis A, Henderson MA, Shackleton M, Haydon A, Mar V, Gyorki DE, Oudit D, Dawson MA, Hicks RJ, Lorigan P, McArthur GA, Marais R, Wong SQ, Dawson SJ
- Issue date: 2019 May 1
- Parallel Analyses of Somatic Mutations in Plasma Circulating Tumor DNA (ctDNA) and Matched Tumor Tissues in Early-Stage Breast Cancer.
- Authors: Zhang X, Zhao W, Wei W, You Z, Ou X, Sun M, Yin Y, Tang X, Zhao Z, Hu C, Liu F, Deng J, Mao L, Zhou D, Ren Y, Li X, Zhang S, Liu C, Geng J, Yao G, Song B, Liu Y, Li D, Jiang Y, Chen Y, Zhao Y, Yu S, Pang D
- Issue date: 2019 Nov 1