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    Personalized detection of circulating tumor DNA antedates breast cancer metastatic recurrence

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    Authors
    Coombes, R
    Page, 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
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    Affiliation
    Surgery and Cancer, Imperial College London
    Issue Date
    2019
    
    Metadata
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    Abstract
    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 Research
    URI
    http://hdl.handle.net/10541/621855
    DOI
    10.1158/1078-0432.CCR-18-3663
    PubMed ID
    30992300
    Additional Links
    https://dx.doi.org/10.1158/1078-0432.CCR-18-3663
    Type
    Article
    Language
    en
    ae974a485f413a2113503eed53cd6c53
    10.1158/1078-0432.CCR-18-3663
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