Mar 15, 2020

Sensitive detection of minimal residual disease in patients treated for early-stage breast cancer

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Heather A ParsonsViktor Adalsteinsson

Abstract

Existing cell-free DNA (cfDNA) methods lack the sensitivity needed for detecting minimal residual disease (MRD) following therapy. We developed a test for tracking hundreds of patient-specific mutations to detect MRD with a 1000-fold lower error rate than conventional sequencing. We compared the sensitivity of our approach to digital droplet PCR (ddPCR) in a dilution series, then retrospectively identified two cohorts of patients who had undergone prospective plasma sampling and clinical data collection: 16 patients with ER+/HER2- metastatic breast cancer (MBC) sampled within six months following metastatic diagnosis and 142 patients with stage 0-III breast cancer who received curative-intent treatment with most sampled at surgery and one year post-op. We performed whole-exome sequencing of tumors and designed individualized MRD tests, which we applied to serial cfDNA samples. Our approach was 100-fold more sensitive than ddPCR when tracking 488 mutations, but most patients had fewer identifiable tumor mutations to track in cfDNA (median 57, range 2-346). Clinical sensitivity was 81% (n=13/16) in newly diagnosed MBC, 23% (n=7/30) at post-op and 19% (n=6/32) at one year in early-stage disease, and highest in patients with the mo...Continue Reading

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Mentioned in this Paper

Whole Exome Sequencing
HER2-positive Carcinoma of Breast
Neoplasm Metastasis
Tracking
Neoplasm, Residual
Nucleic Acid Sequencing
Detection
Diagnosis
Cell-Free DNA
Gene Mutation

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