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

Eleonor Olsson, Christof Winter, Anthony George, Yilun Chen, Jillian Howlin, Man-Hung Eric Tang, Malin Dahlgren, Ralph Schulz, Dorthe Grabau, Danielle van Westen, Mårten Fernö, Christian Ingvar, Carsten Rose, Pär-Ola Bendahl, Lisa Rydén, Åke Borg, Sofia Gruvberger, Helena Jernström, Lao Saal

Research output: Contribution to journalArticlepeer-review

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.
Original languageEnglish
Pages (from-to)1034-1047
JournalEMBO Molecular Medicine
Volume7
Issue number8
DOIs
Publication statusPublished - 2015

Subject classification (UKÄ)

  • Cell and Molecular Biology

Fingerprint

Dive into the research topics of 'Serial monitoring of circulating tumor DNA in patients with primary breast cancer for detection of occult metastatic disease.'. Together they form a unique fingerprint.

Cite this