Serial monitoring of circulating tumor DNA in patients with primary breast cancer for detection of occult metastatic disease.
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/5448824
- author
- organization
- publishing date
- 2015
- 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}}, }