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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 orcid , 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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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
EMBO Molecular Medicine
volume
7
issue
8
pages
1034 - 1047
publisher
Wiley-Blackwell
external identifiers
  • pmid:25987569
  • wos:000359070600007
  • scopus:84938414305
  • pmid:25987569
ISSN
1757-4684
DOI
10.15252/emmm.201404913
project
Translational development and clinical applications of circulating tumor DNA for patient stratification, therapy guidance, and disease monitoring
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
2016-04-01 09:50:10
date last changed
2022-09-03 07:37:39
@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    = {{Wiley-Blackwell}},
  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}},
  doi          = {{10.15252/emmm.201404913}},
  volume       = {{7}},
  year         = {{2015}},
}