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Serial monitoring of circulating tumor DNA in patients with primary breast cancer for detection of occult metastatic disease.

Olsson, Eleonor LU ; Winter, Christof LU ; George, Anthony LU ; Chen, Yilun LU ; Howlin, Jillian LU ; Tang, Man-Hung Eric LU ; Dahlgren, Malin LU ; Schulz, Ralph LU ; Grabau, Dorthe LU and van Westen, Danielle LU , et al. (2015) In EMBO Molecular Medicine 7(8). p.1034-1047
Abstract
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... (More)
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. (Less)
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publication status
published
subject
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EMBO Molecular Medicine
volume
7
issue
8
pages
1034 - 1047
publisher
Federation of European Neuroscience Societies and Blackwell Publishing Ltd
external identifiers
  • pmid:25987569
  • wos:000359070600007
  • scopus:84938414305
ISSN
1757-4684
DOI
10.15252/emmm.201404913
project
CREATE Health
language
English
LU publication?
yes
id
b71f40ff-d1be-4587-9c45-6d147001f649 (old id 5448824)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/25987569?dopt=Abstract
date added to LUP
2015-06-05 00:05:42
date last changed
2017-11-05 03:00:50
@article{b71f40ff-d1be-4587-9c45-6d147001f649,
  abstract     = {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.},
  author       = {Olsson, Eleonor and Winter, Christof and George, Anthony and Chen, Yilun and Howlin, Jillian and Tang, Man-Hung Eric and Dahlgren, Malin and Schulz, Ralph and Grabau, Dorthe and van Westen, Danielle and Fernö, Mårten and Ingvar, Christian and Rose, Carsten and Bendahl, Pär-Ola and Rydén, Lisa and Borg, Åke and Gruvberger, Sofia and Jernström, Helena and Saal, Lao},
  issn         = {1757-4684},
  language     = {eng},
  number       = {8},
  pages        = {1034--1047},
  publisher    = {Federation of European Neuroscience Societies and Blackwell Publishing Ltd},
  series       = {EMBO Molecular Medicine},
  title        = {Serial monitoring of circulating tumor DNA in patients with primary breast cancer for detection of occult metastatic disease.},
  url          = {http://dx.doi.org/10.15252/emmm.201404913},
  volume       = {7},
  year         = {2015},
}