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Personalized detection of circulating tumor DNA antedates breast cancer metastatic recurrence.

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journal contribution
posted on 26.04.2019, 13:42 by C Coombes, K Page, R Salari, RK Hastings, AC Armstrong, S Ahmed, S Ali, SJ Cleator, LM Kenny, J Stebbing, MJ Rutherford, H Sethi, AR Boydell, R Swenerton, D Fernandez-Garcia, K Gleason, KS Goddard, DS Guttery, Z Assaf, H-T Wu, P Natarajan, DA Moore, L Primrose, S Dashner, AS Tin, M Balcioglu, R Srinivasa, S Shchegrova, AG Olson, D Hafez, P Billings, A Aleshin, F Rehman, B Toghill, AH Hills, MC Louie, C-HJ Lin, BG Zimmermann, JA Shaw
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.

Funding

This study was supported by programme grant funding from Cancer Research UK to Shaw and Coombes (C14315/A13462 and C14315/A23464).

History

Citation

Clinical Cancer Research, 2019

Author affiliation

/Organisation/COLLEGE OF LIFE SCIENCES/School of Medicine/Department of Health Sciences

Version

AM (Accepted Manuscript)

Published in

Clinical Cancer Research

Publisher

American Association for Cancer Research

issn

1078-0432

Acceptance date

11/04/2019

Copyright date

2019

Publisher version

http://clincancerres.aacrjournals.org/content/early/2019/04/26/1078-0432.CCR-18-3663

Notes

The file associated with this record is under embargo until 12 months after publication, in accordance with the publisher's self-archiving policy. The full text may be available through the publisher links provided above.

Language

en