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Analysis of Circulating Tumor DNA to Monitor Metastatic Breast Cancer

Sarah‐Jane DawsonDepartment of Oncology, University of Cambridge and Cancer Research UK Cambridge Institute, Li Ka Shing Centre, Cambridge, United KingdomDana W.Y. TsuiDepartment of Oncology, University of Cambridge and Cancer Research UK Cambridge Institute, Li Ka Shing Centre, Addenbrooke's Hospital, Cambridge University Hospital National Health Service Foundation Trust and National Institute for Health Research Cambridge Biomedical Research CentreMuhammed MurtazaDepartment of Oncology, University of Cambridge and Cancer Research UK Cambridge Institute, Li Ka Shing Centre, Addenbrooke's Hospital, Cambridge University Hospital National Health Service Foundation Trust and National Institute for Health Research Cambridge Biomedical Research CentreHeather BiggsCambridge Breast Unit, Addenbrooke's Hospital, Cambridge University Hospital National Health Service Foundation Trust and National Institute for Health Research Cambridge Biomedical Research CentreOscar M. RuedaDepartment of Oncology, University of Cambridge and Cancer Research UK Cambridge Institute, Li Ka Shing Centre, Addenbrooke's Hospital, Cambridge University Hospital National Health Service Foundation Trust and National Institute for Health Research Cambridge Biomedical Research CentreSuet‐Feung ChinDepartment of Oncology, University of Cambridge and Cancer Research UK Cambridge Institute, Li Ka Shing Centre, Addenbrooke's Hospital, Cambridge University Hospital National Health Service Foundation Trust and National Institute for Health Research Cambridge Biomedical Research CentreMark DunningDepartment of Oncology, University of Cambridge and Cancer Research UK Cambridge Institute, Li Ka Shing Centre, Addenbrooke's Hospital, Cambridge University Hospital National Health Service Foundation Trust and National Institute for Health Research Cambridge Biomedical Research CentreDavina GaleDepartment of Oncology, University of Cambridge and Cancer Research UK Cambridge Institute, Li Ka Shing Centre, Addenbrooke's Hospital, Cambridge University Hospital National Health Service Foundation Trust and National Institute for Health Research Cambridge Biomedical Research CentreTim ForshewDepartment of Oncology, University of Cambridge and Cancer Research UK Cambridge Institute, Li Ka Shing Centre, Addenbrooke's Hospital, Cambridge University Hospital National Health Service Foundation Trust and National Institute for Health Research Cambridge Biomedical Research CentreBetania Mahler‐AraujoDepartments of Histopathology, Addenbrooke's Hospital, Cambridge University Hospital National Health Service Foundation Trust and National Institute for Health Research Cambridge Biomedical Research CentreSabrina RajanCambridge Breast Unit, Addenbrooke's Hospital, Cambridge University Hospital National Health Service Foundation Trust and National Institute for Health Research Cambridge Biomedical Research CentreSean HumphrayIllumina, Little ChesterfordJennifer BecqIllumina, Little ChesterfordDavid HalsallClinical Biochemistry and Immunology, Addenbrooke's Hospital, Cambridge University Hospital National Health Service Foundation Trust and National Institute for Health Research Cambridge Biomedical Research CentreMatthew WallisRadiology, Addenbrooke's Hospital, Cambridge University Hospital National Health Service Foundation Trust and National Institute for Health Research Cambridge Biomedical Research CentreDavid BentleyIllumina, Little ChesterfordCarlos CaldasCambridge Experimental Cancer Medicine Centre, CambridgeNitzan RosenfeldDepartment of Oncology, University of Cambridge and Cancer Research UK Cambridge Institute, Li Ka Shing Centre, Addenbrooke's Hospital, Cambridge University Hospital National Health Service Foundation Trust and National Institute for Health Research Cambridge Biomedical Research Centre

2013en

ABI

Annotatsiya

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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DOI: 10.1056/nejmoa1213261

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