Serial monitoring of circulating tumor DNA in patients with primary breast cancer for detection of occult metastatic disease.
- Oncology and Pathology, MV
- Surgery (Lund)
- Oncology and Pathology, Kamprad Lab
- Diagnostic Radiology, (Lund)
Publishing year: 2015
Publication/Series: EMBO Molecular Medicine
Document type: Journal article
Publisher: Federation of European Neuroscience Societies and Blackwell Publishing Ltd
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.
- Cell and Molecular Biology
- CREATE Health
- ISSN: 1757-4684