Detection of minimal residual disease and prediction of recurrence in breast cancer using a plasma-only circulating tumor DNA assay
Wolfgang Janni, B Rack, Thomas W. P. Friedl, AD Hartkopf, Lisa Wiesmüller, Kerstin Pfister, Franziska Mergel, Aaron S. Fink, T. Braun, F. Mehmeti, N. Uhl, A de Gregorio, J. Huober, Tanja Fehm, Volkmar Müller, Thereasa A. Rich, Derek Dustin, Siyuan Zhang, Sophia Huesmann
Abstract
BACKGROUND: Detection of minimal residual disease (MRD) in early breast cancer (EBC) after curative-intent treatment may identify patients at risk for recurrence. Most circulating tumor DNA (ctDNA)-based MRD assays require knowledge of genomic alterations from tumor tissue. However, tissue availability may be limited in some patients. Here, we evaluated sensitivity and specificity for recurrence detection, using a plasma-only ctDNA MRD assay. MATERIALS AND METHODS: For this pilot study, 47 plasma samples from 38 EBC patients were collected at 12 or 36 months post-diagnosis or at clinical recurrence. ctDNA presence was determined by a custom bioinformatics classifier that identifies tumor-derived somatic variants and methylation profiles specific to individual cancer types using a 5-Mb next-generation sequencing panel. RESULTS: ctDNA was detected at or before distant recurrence in 11/14 (79%) patients [sensitivity was 85% (11/13) among samples collected within 2 years from recurrence]. Lead time was evaluable in 4/6 (67%) samples collected before distant recurrence with detectable ctDNA and ranged from 3.4 to 18.5 months. ctDNA was not detected in samples from patients without recurrence (n = 13). CONCLUSIONS: This study demonstrates the feasibility of MRD detection in EBC using a plasma-only multiomic ctDNA-based approach. Larger studies are ongoing to further validate the clinical performance of the assay and demonstrate its applications.