Serial monitoring of circulating tumor DNA in patients with primary breast cancer for detection of occult metastatic disease.
Författare
Summary, in English
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.
Avdelning/ar
- Bröstcancer-genetik
- Kirurgi, Lund
- Tumörmikromiljö
- Neuroradiologi
- Diagnostisk radiologi, Lund
- BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
Publiceringsår
2015
Språk
Engelska
Sidor
1034-1047
Publikation/Tidskrift/Serie
EMBO Molecular Medicine
Volym
7
Issue
8
Länkar
Dokumenttyp
Artikel i tidskrift
Förlag
Wiley-Blackwell
Ämne
- Cell and Molecular Biology
Status
Published
Projekt
- Translational development and clinical applications of circulating tumor DNA for patient stratification, therapy guidance, and disease monitoring
Forskningsgrupp
- Neuroradiology
ISBN/ISSN/Övrigt
- ISSN: 1757-4684