Analysis of Circulating Tumor DNA to Monitor Metastatic Breast Cancer
Open accessAbstract
BACKGROUND: The management of metastatic breast cancer requires monitoring of the tumor burden to determine the response to treatment, and improved biomarkers are needed. Biomarkers such as cancer antigen 15-3 (CA 15-3) and circulating tumor cells have been widely studied. However, circulating cell-free DNA carrying tumor-specific alterations (circulating tumor DNA) has not been extensively investigated or compared with other circulating biomarkers in breast cancer. METHODS: We compared the radiographic imaging of tumors with the assay of circulating tumor DNA, CA 15-3, and circulating tumor cells in 30 women with metastatic breast cancer who were receiving systemic therapy. We used targeted or whole-genome sequencing to identify somatic genomic alterations and designed personalized assays to quantify circulating tumor DNA in serially collected plasma specimens. CA 15-3 levels and numbers of circulating tumor cells were measured at identical time points. RESULTS: Circulating tumor DNA was successfully detected in 29 of the 30 women (97%) in whom somatic genomic alterations were identified; CA 15-3 and circulating tumor cells were detected in 21 of 27 women (78%) and 26 of 30 women (87%), respectively. Circulating tumor DNA levels showed a greater dynamic range, and greater correlation with changes in tumor burden, than did CA 15-3 or circulating tumor cells. Among the measures tested, circulating tumor DNA provided the earliest measure of treatment response in 10 of 19 women (53%). CONCLUSIONS: This proof-of-concept analysis showed that circulating tumor DNA is an informative, inherently specific, and highly sensitive biomarker of metastatic breast cancer. (Funded by Cancer Research UK and others.).
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- Authors
- Dawson, S.-J., Tsui, D. W. Y., Murtaza, M., Biggs, H., Rueda, O. M., Chin, S.-F., Dunning, M. J., Gale, D., Forshew, T., Mahler-Araujo, B., Rajan, S., Humphray, S., Becq, J., Halsall, D., Wallis, M., Bentley, D., Caldas, C., & Rosenfeld, N.
- Affiliations
- University of Cambridge (GB)
- National Health Service (GB)
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2013-03-28
- Volume
- 368
- Issue
- 13
- Pages
- 1199-1209
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2140575188
- Cited by
- 2,207
- References
- 44
- Citations by year
- 2026: 86 · 2025: 96 · 2024: 106 · 2023: 109 · 2022: 169 · 2021: 180 · 2020: 197 · 2019: 220 · 2018: 197 · 2017: 224 · 2016: 204 · 2015: 195 · 2014: 135 · 2013: 82 · 2012: 1
- FWCI
- 72.15
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Cancer Research UK (11906, 16942, 22310)
- National Institute for Health and Care Research (NF-SI-0611-10154)
- NIHR Cambridge Biomedical Research Centre
- Cancer Research UK Cambridge Institute, University of Cambridge
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › BRCA gene mutations in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
- Keywords
- circulating tumor DNA, metastatic breast cancer, liquid biopsy, CA15-3, circulating tumor cells, treatment response monitoring, tumor burden, somatic alterations, circulating biomarkers, early detection of treatment response
- MeSH terms
- Breast Neoplasms, DNA, Neoplasm, Female, Humans, Mutation, Neoplasm Metastasis, Prognosis, Radiography, Sensitivity and Specificity, Biomarkers, Tumor, Sequence Analysis, DNA, Mucin-1, Tumor Burden, Genome-Wide Association Study
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