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Personalized detection of circulating tumor DNA antedates breast cancer metastatic recurrence
Publication available at: | https://discovery.ucl.ac.uk/id/eprint/10072629/ |
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Title: | Personalized detection of circulating tumor DNA antedates breast cancer metastatic recurrence |
Authors: | Coombes, RC Page, K Salari, R Hastings, RK Armstrong, A Ahmed, S Ali, S Cleator, S Kenny, L Stebbing, J Rutherford, M Sethi, H Boydell, A Swenerton, R Fernandez-Garcia, D Gleason, KLT Goddard, K Guttery, DS Assaf, ZJ Wu, H-T Natarajan, P Moore, DA Primrose, L Dashner, S Tin, AS Balcioglu, M Srinivasan, R Shchegrova, SV Olson, A Hafez, D Billings, P Aleshin, A Rehman, F Toghill, BJ Hills, A Louie, MC Lin, C-HJ Zimmermann, BG Shaw, JA |
Item Type: | Journal Article |
Abstract: | Purpose: Up to 30% of patients with breast cancer 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 circulating tumor DNA (ctDNA) profiling for detection of recurrence in breast cancer. Experimental Design: Forty-nine primary patients with breast cancer 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 ultradeep sequencing (average >100,000X). Results: Plasma ctDNA was detected ahead of clinical or radiologic 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 nonrelapsing 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, whereas 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 patients with breast cancer. More importantly, earlier detection of up to 2 years provides a possible window for therapeutic intervention. |
Issue Date: | 15-Jul-2019 |
Date of Acceptance: | 11-Apr-2019 |
URI: | http://hdl.handle.net/10044/1/84448 |
DOI: | 10.1158/1078-0432.CCR-18-3663 |
ISSN: | 1078-0432 |
Publisher: | American Association for Cancer Research |
Start Page: | 4255 |
End Page: | 4263 |
Journal / Book Title: | Clinical Cancer Research |
Volume: | 25 |
Issue: | 14 |
Copyright Statement: | ©2019 American Association for Cancer Research. |
Sponsor/Funder: | National Institute for Health Research Imperial College Healthcare NHS Trust- BRC Funding |
Funder's Grant Number: | NIHR-RP-011-053 RDB01 79560 |
Keywords: | Science & Technology Life Sciences & Biomedicine Oncology CLINICAL-PRACTICE GUIDELINES DROPLET DIGITAL PCR CELL-FREE DNA NEOADJUVANT CHEMOTHERAPY PERIPHERAL-BLOOD DIAGNOSIS QUANTIFICATION MUTATIONS PLASMA CEA Adult Aged Aged, 80 and over Biomarkers, Tumor Breast Neoplasms Circulating Tumor DNA Female High-Throughput Nucleotide Sequencing Humans Middle Aged Mutation Neoplasm Metastasis Neoplasm Recurrence, Local Precision Medicine Prognosis Prospective Studies Humans Breast Neoplasms Neoplasm Metastasis Neoplasm Recurrence, Local Prognosis Prospective Studies Mutation Adult Aged Aged, 80 and over Middle Aged Female High-Throughput Nucleotide Sequencing Biomarkers, Tumor Precision Medicine Circulating Tumor DNA Science & Technology Life Sciences & Biomedicine Oncology CLINICAL-PRACTICE GUIDELINES DROPLET DIGITAL PCR CELL-FREE DNA NEOADJUVANT CHEMOTHERAPY PERIPHERAL-BLOOD DIAGNOSIS QUANTIFICATION MUTATIONS PLASMA CEA 1112 Oncology and Carcinogenesis Oncology & Carcinogenesis |
Publication Status: | Published |
Open Access location: | https://discovery.ucl.ac.uk/id/eprint/10072629/ |
Online Publication Date: | 2019-04-16 |
Appears in Collections: | Department of Surgery and Cancer Division of Cancer |