EMBO Molecular Medicine | |
Serial monitoring of circulating tumor DNA in patients with primary breast cancer for detection of occult metastatic disease | |
Eleonor Olsson5  Christof Winter5  Anthony George5  Yilun Chen5  Jillian Howlin5  Man-Hung Eric Tang5  Malin Dahlgren5  Ralph Schulz5  Dorthe Grabau3  Danielle van Westen1  Mårten Fernö5  Christian Ingvar2  Carsten Rose4  Pär-Ola Bendahl5  Lisa Rydén4  Åke Borg5  Sofia K Gruvberger-Saal5  Helena Jernström5  | |
[1] Department of Radiology, Skåne University Hospital, Lund, Sweden;Department of Surgery, Lund University and Skåne University Hospital, Lund, Sweden;Department of Pathology, Skåne University Hospital, Lund, Sweden;Lund University Cancer Center, Lund, Sweden;Division of Oncology and Pathology, Department of Clinical Sciences, Lund University, Lund, Sweden | |
关键词: breast carcinoma; circulating tumor DNA; early detection; liquid biopsy; metastasis; | |
DOI : 10.15252/emmm.201404913 | |
来源: Wiley | |
【 摘 要 】
Metastatic breast cancer is usually diagnosed after becoming symptomatic, at which point it is rarely curable. Cell-free circulating tumor DNA (ctDNA) contains tumor-specific chromosomal rearrangements that may be interrogated in blood plasma. We evaluated serial monitoring of ctDNA for earlier detection of metastasis in a retrospective study of 20 patients diagnosed with primary breast cancer and long follow-up. Using an approach combining low-coverage whole-genome sequencing of primary tumors and quantification of tumor-specific rearrangements in plasma by droplet digital PCR, we identify for the first time that ctDNA monitoring is highly accurate for postsurgical discrimination between patients with (93%) and without (100%) eventual clinically detected recurrence. ctDNA-based detection preceded clinical detection of metastasis in 86% of patients with an average lead time of 11 months (range 0–37 months), whereas patients with long-term disease-free survival had undetectable ctDNA postoperatively. ctDNA quantity was predictive of poor survival. These findings establish the rationale for larger validation studies in early breast cancer to evaluate ctDNA as a monitoring tool for early metastasis detection, therapy modification, and to aid in avoidance of overtreatment. Serial measurement of circulating tumor DNA (ctDNA) is shown to be a robust and accurate occult metastatic disease biomarker in patients diagnosed with primary breast cancer. Measured ctDNA levels are a quantitative risk factor for poor outcomes.Abstract
Synopsis
【 授权许可】
CC BY
© 2015 The Authors. Published under the terms of the CC BY 4.0 license
Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
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