The DOI matches its Crossref record; 43 of the 44 references it cites were found in a registry or an index.
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.).
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“it has recently become apparent that vertebrate specific chromatin complexes such as the HUSH complex can be major regulators of the LINE-1 family of retrotransposons 218,219 .”
From The roles of DNA, RNA and histone methylation in ageing and cancer (2019) · cites this paper as [219]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
An Introduction to the Bootstrap
Efron, B., & Tibshirani, R. J. (1994) · doi:10.1201/9780429246593 · Cited by 40,500
New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1)
Eisenhauer, E. A., Therasse, P., Bogaerts, J., Schwartz, L. H., Sargent, D., Ford, R., Dancey, J., Arbuck, S., Gwyther, S., Mooney, M., et al. (2009) · European Journal of Cancer · doi:10.1016/j.ejca.2008.10.026 · Cited by 29,534
Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008
Ferlay, J., Shin, H., Bray, F., Forman, D., Mathers, C. D., & Parkin, D. M. (2010) · International Journal of Cancer · doi:10.1002/ijc.25516 · Cited by 21,468
An Introduction to the Bootstrap
Efron, B., & Tibshirani, R. J. (1993) · doi:10.1007/978-1-4899-4541-9 · Cited by 21,230
Comprehensive molecular portraits of human breast tumours
The Cancer Genome Atlas Network (2012) · Nature · doi:10.1038/nature11412 · Cited by 12,129
The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups
METABRIC Group, Curtis, C., Shah, S. P., Chin, S.-F., Turashvili, G., Rueda, O. M., Dunning, M. J., Speed, D., Lynch, A. G., Samarajiwa, S., et al. (2012) · Nature · doi:10.1038/nature10983 · Cited by 6,097
Self-citationCirculating Tumor Cells, Disease Progression, and Survival in Metastatic Breast Cancer
Cristofanilli, M., Budd, G. T., Ellis, M. J., Stopeck, A., Matera, J., Miller, M. C., Reuben, J. M., Doyle, G. V., Allard, W. J., Terstappen, L. W. M. M., et al. (2004) · New England Journal of Medicine · doi:10.1056/nejmoa040766 · Cited by 4,602
Cox’s regression model for counting processes: A large sample study
Andersen, P. K., & Gill, R. D. (1982) · The Annals of Statistics · doi:10.1214/aos/1176345976 · Cited by 4,419
Isolation of rare circulating tumour cells in cancer patients by microchip technology
Nagrath, S., Sequist, L. V. D., Maheswaran, S., Bell, D. W., Irimia, D., Ulkus, L., Smith, M. R., Kwak, E. L., Digumarthy, S. R., Muzikansky, A., et al. (2007) · Nature · doi:10.1038/nature06385 · Cited by 3,595
Cell-free nucleic acids as biomarkers in cancer patients
Schwarzenbach, H., Hoon, D. S. �., & Pantel, K. (2011) · Nature reviews. Cancer · doi:10.1038/nrc3066 · Cited by 2,897
Circulating mutant DNA to assess tumor dynamics
Diehl, F., Schmidt, K., Choti, M. A., Romans, K. E., Goodman, S. N., Li, M., Thornton, K. A., Agrawal, N., Sokoll, L. J., Szabo, S., et al. (2008) · Nature Medicine · doi:10.1038/nm.1789 · Cited by 2,746
COSMIC: mining complete cancer genomes in the Catalogue of Somatic Mutations in Cancer
Forbes, S. A., Bindal, N., Bamford, S., Cole, C., Kok, C. Y., Beare, D., Jia, M., Shepherd, R., Leung, K., Menzies, A., et al. (2011) · Nucleic Acids Research · doi:10.1093/nar/gkq929 · Cited by 2,278
Harris, L. N., Fritsche, H. A., Mennel, R. G., Norton, L., Ravdin, P. M., Taube, S. E., Somerfield, M. R., Hayes, D. F., & Bast, R. C. (2007) · Journal of Clinical Oncology · doi:10.1200/jco.2007.14.2364 · Cited by 2,234
The clonal and mutational evolution spectrum of primary triple-negative breast cancers
Shah, S. P., Roth, A., Goya, R., Oloumi, A., Ha, G., Zhao, Y., Turashvili, G., Ding, J., Tse, K., Haffari, G., et al. (2012) · Nature · doi:10.1038/nature10933 · Cited by 1,967
Self-citationEmergence of KRAS mutations and acquired resistance to anti-EGFR therapy in colorectal cancer
Misale, S., Yaeger, R., Hobor, S., Scala, E., Janakiraman, M., Liska, D., Valtorta, E., Schiavo, R., Buscarino, M., Siravegna, G., et al. (2012) · Nature · doi:10.1038/nature11156 · Cited by 1,889
Vogelstein, B., & Kinzler, K. W. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.16.9236 · Cited by 1,770
The landscape of cancer genes and mutational processes in breast cancer
Stephens, P. J., Tarpey, P. S., Davies, H. R., Loo, P. V., Greenman, C., Wedge, D. C., Nik‐Zainal, S., Martin, S., Varela, I., Bignell, G. R., et al. (2012) · Nature · doi:10.1038/nature11017 · Cited by 1,731
Self-citationThe molecular evolution of acquired resistance to targeted EGFR blockade in colorectal cancers
Diaz Jr, L. A., Williams, R. T., Wu, J., Kinde, I., Hecht, J. R., Berlin, J., Allen, B., Bozic, I., Reiter, J. G., Nowak, M. A., et al. (2012) · Nature · doi:10.1038/nature11219 · Cited by 1,713
Forshew, T., Murtaza, M., Parkinson, C., Gale, D. G., Tsui, D. W. Y., Kaper, F., Dawson, S., Piskorz, A., Jimenez‐Liñan, M., Bentley, D., et al. (2012) · Science Translational Medicine · doi:10.1126/scitranslmed.3003726 · Cited by 1,308
Self-citationSequence analysis of mutations and translocations across breast cancer subtypes
Banerji, S. O., Cibulskis, K., Rangel‐Escareño, C., Brown, K., Carter, S. L., Frederick, A. M., Lawrence, M. S., Sivachenko, A., Sougnez, C. L., Zou, L., et al. (2012) · Nature · doi:10.1038/nature11154 · Cited by 1,181
Detection and quantification of rare mutations with massively parallel sequencing
Kinde, I., Wu, J., Papadopoulos, N., Kinzler, K. W., & Vogelstein, B. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1105422108 · Cited by 1,144
Detection, clinical relevance and specific biological properties of disseminating tumour cells
Pantel, K., Brakenhoff, R. H., & Brandt, B. (2008) · Nature reviews. Cancer · doi:10.1038/nrc2375 · Cited by 1,116
Whole-genome analysis informs breast cancer response to aromatase inhibition
Ellis, M. J., Ding, L., Shen, D., Luo, J. R., Suman, V. J., Wallis, J. W., Tine, B. A. V., Hoog, J., Goiffon, R., Goldstein, T. C., et al. (2012) · Nature · doi:10.1038/nature11143 · Cited by 1,040
Complex landscapes of somatic rearrangement in human breast cancer genomes
Stephens, P. J., McBride, D. J., Lin, M., Varela, I., Pleasance, E., Simpson, J. T., Stebbings, L. A., Leroy, C., Edkins, S., Mudie, L. J., et al. (2009) · Nature · doi:10.1038/nature08645 · Cited by 850
Leary, R. J., Sausen, M., Kinde, I., Papadopoulos, N., Carpten, J. D., Craig, D. W., O’Shaughnessy, J., Kinzler, K. W., Parmigiani, G., Vogelstein, B., et al. (2012) · Science Translational Medicine · doi:10.1126/scitranslmed.3004742 · Cited by 633
Development of Personalized Tumor Biomarkers Using Massively Parallel Sequencing
Leary, R. J., Kinde, I., Diehl, F., Schmidt, K., Clouser, C., Duncan, C., Antipova, A. A., Lee, C. C., McKernan, K. J., Vega, F. M. D. L., et al. (2010) · Science Translational Medicine · doi:10.1126/scitranslmed.3000702 · Cited by 519
Chan, K. A., Jiang, P., Zheng, Y. W. L., Liao, G. J. W., Sun, H., Wong, J., Siu, S. S. N., Chan, W. C., Chan, S. L., Chan, A. T. �., et al. (2012) · Clinical Chemistry · doi:10.1373/clinchem.2012.196014 · Cited by 487
Gormally, E., Caboux, É., Vineis, P., & Hainaut, P. L. (2007) · Mutation Research/Reviews in Mutation Research · doi:10.1016/j.mrrev.2006.11.002 · Cited by 444
Digital PCR for the molecular detection of fetal chromosomal aneuploidy
Lo, Y. M. D., Lun, F. M. F., Chan, K. C. A., Tsui, N. B. Y., Chong, K. C., Lau, T. K., Leung, T. Y., Zee, B. C.-Y., Cantor, C. R., & Chiu, R. W. K. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0705765104 · Cited by 434
Yung, T., Chan, K. C. A., Mok, T. S. K., TONG, J. H. M., To, K., & Lo, Y. M. D. (2009) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-08-2622 · Cited by 386
CA 15-3: Uses and limitation as a biomarker for breast cancer
Duffy, M. J., Evoy, D., & McDermott, E. (2010) · Clinica Chimica Acta · doi:10.1016/j.cca.2010.08.039 · Cited by 373
Detection of Tumor PIK3CA Status in Metastatic Breast Cancer Using Peripheral Blood
Higgins, M. J., Jelovac, D., Barnathan, E., Blair, B., Slater, S. A., Powers, P., Zorzi, J., Jeter, S. C., Oliver, G. R., Fetting, J. H., et al. (2012) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-11-2696 · Cited by 311
Pierga, J., Hajage, D., Bachelot, T., Delaloge, S., Brain, E. G. C., Campone, M., Dieras, V. C., Rolland, E., Mignot, L., Mathiot, C., et al. (2011) · Annals of Oncology · doi:10.1093/annonc/mdr263 · Cited by 281
Lianidou, E. S., & Markou, A. N. (2011) · Clinical Chemistry · doi:10.1373/clinchem.2011.165068 · Cited by 265
McBride, D. J., Orpana, A., Sotiriou, C. P., Joensuu, H., Stephens, P. J., Mudie, L. J., Hämäläinen, E., Stebbings, L. A., Andersson, L. C., Flanagan, A. M., et al. (2010) · Genes Chromosomes and Cancer · doi:10.1002/gcc.20815 · Cited by 194
Detecting tumor-related alterations in plasma or serum DNA of patients diagnosed with breast cancer.
Chen, X., Bonnefoi, H. R., Diebold‐Berger, S., Lyautey, J., Lederrey, C., Faltin-Traub, E. F., Stroun, M., & Anker, P. (1999) · PubMed · Cited by 193
Genomic analysis of circulating cell-free DNA infers breast cancer dormancyPreprint
Shaw, J., Page, K., Blighe, K., Hava, N., Guttery, D. S., Ward, B., Brown, J., Ruangpratheep, C., Stebbing, J., Payne, R., et al. (2011) · Genome Research · doi:10.1101/gr.123497.111 · Cited by 182
Characterization of metastatic breast cancer patients with nondetectable circulating tumor cells
Mego, M., Giorgi, U. D., Dawood, S., Wang, X., Valero, V., Andreopoulou, E., Handy, B. C., Ueno, N. T., Reuben, J. M., & Cristofanilli, M. (2010) · International Journal of Cancer · doi:10.1002/ijc.25690 · Cited by 115
Quantifying EGFR Alterations in the Lung Cancer Genome with Nanofluidic Digital PCR Arrays
Wang, J., Ramakrishnan, R., Tang, Z., Fan, W., Kluge, A., Dowlati, A., Jones, R. C., & Ma, P. C. (2010) · Clinical Chemistry · doi:10.1373/clinchem.2009.134973 · Cited by 99
Nakamura, T., Sueoka‐Aragane, N., Iwanaga, K., Sato, A., Komiya, K., Abe, T., Ureshino, N., Hayashi, S., Hosomi, T., Hirai, M., et al. (2011) · Journal of Thoracic Oncology · doi:10.1097/jto.0b013e31822956e8 · Cited by 74
Lauro, S. D., Trasatti, L., Bordin, F., Lanzetta, G., Bria, E., Gelibter, A. J., Reale, M. G., & Vecchione, A. M. (1999) · PubMed · Cited by 56
Lianidou, E. S., & Markou, A. N. (2012) · Laboratory Medicine Online · doi:10.3343/lmo.2012.2.2.59 · Cited by 53
Detection of p53 mutations in the plasma DNA of patients with ovarian cancer
Otsuka, J., Okuda, T., Sekizawa, A., Amemiya, S., Saito, H., Okai, T., & Kushima, M. (2004) · International Journal of Gynecological Cancer · doi:10.1111/j.1048-891x.2004.014305.x · Cited by 45
Flagged first, then by citations
1 of the 44 references couldn’t be matched to a known paper.
Research works printed but not linked: 2
- Lauro S, 1999, Anticancer Res, 19, 3511
- Chen X, 1999, Clin Cancer Res, 5, 2297
Cited by
Sorted by citations
Detection of Circulating Tumor DNA in Early- and Late-Stage Human Malignancies
Bettegowda, C., Sausen, M., Leary, R. J., Kinde, I., Wang, Y., Agrawal, N., Bartlett, B. R., Wang, H., Luber, B., Alani, R. M., et al. (2014) · Science Translational Medicine · doi:10.1126/scitranslmed.3007094 · Cited by 5,067
ESMO consensus guidelines for the management of patients with metastatic colorectal cancer
Van Cutsem, E., Cervantes, A., Adam, R., Sobrero, A., Van Krieken, J. H., Aderka, D., Aranda Aguilar, E., Bardelli, A., Benson, A., Bodoky, G., et al. (2016) · Annals of Oncology · doi:10.1093/annonc/mdw235 · Cited by 3,421
Clonal heterogeneity and tumor evolution: past, present, and the future
McGranahan, N., & Swanton, C. (2017) · Cell · doi:10.1016/j.cell.2017.01.018 · Cited by 2,840
Liquid biopsies come of age: Towards implementation of circulating tumour DNA
Wan, J. C. M., Massie, C., Garcia-Corbacho, J., Mouliere, F., Brenton, J. D., Caldas, C., Pacey, S., Baird, R., & Rosenfeld, N. (2017) · Nature Reviews Cancer · doi:10.1038/nrc.2017.7 · Cited by 2,809
Self-citationDetection and localization of surgically resectable cancers with a multi-analyte blood test
Cohen, J. D., Li, L., Wang, Y., Thoburn, C., Afsari, B., Danilova, L., Douville, C., Javed, A. A., Wong, F., Mattox, A., et al. (2018) · Science · doi:10.1126/science.aar3247 · Cited by 2,783
Metadata
- 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
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
