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Personalized detection of circulating tumor DNA antedates breast cancer metastatic recurrence

Coombes, C; Page, K; Salari, R; Hastings, RK; Armstrong, AC; Ahmed, S; Ali, S; ... Shaw, JA; + view all (2019) Personalized detection of circulating tumor DNA antedates breast cancer metastatic recurrence. Clinical Cancer Research 10.1158/1078-0432.CCR-18-3663. (In press).

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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.

Type: Article
Title: Personalized detection of circulating tumor DNA antedates breast cancer metastatic recurrence
Location: United States
DOI: 10.1158/1078-0432.CCR-18-3663
Publisher version: https://doi.org/10.1158/1078-0432.CCR-18-3663
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Pathology
URI: http://discovery.ucl.ac.uk/id/eprint/10072629
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