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• W4361959413 abstract "<div>AbstractPurpose:<p>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 1,000-fold lower error rate than conventional sequencing.</p>Experimental Design:<p>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 6 months following metastatic diagnosis and 142 patients with stage 0 to III breast cancer who received curative-intent treatment with most sampled at surgery and 1 year postoperative. We performed whole-exome sequencing of tumors and designed individualized MRD tests, which we applied to serial cfDNA samples.</p>Results:<p>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% (<i>n</i> = 13/16) in newly diagnosed MBC, 23% (<i>n</i> = 7/30) at postoperative and 19% (<i>n</i> = 6/32) at 1 year in early-stage disease, and highest in patients with the most tumor mutations available to track. MRD detection at 1 year was strongly associated with distant recurrence [HR = 20.8; 95% confidence interval, 7.3–58.9]. Median lead time from first positive sample to recurrence was 18.9 months (range = 3.4–39.2 months).</p>Conclusions:<p>Tracking large numbers of individualized tumor mutations in cfDNA can improve MRD detection, but its sensitivity is driven by the number of tumor mutations available to track.</p></div>" @default.
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• W4361959413 date "2023-03-31" @default.
• W4361959413 modified "2023-09-24" @default.
• W4361959413 title "Data from Sensitive Detection of Minimal Residual Disease in Patients Treated for Early-Stage Breast Cancer" @default.
• W4361959413 doi "https://doi.org/10.1158/1078-0432.c.6530084" @default.
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