Sensitive Detection of Minimal Residual Disease in Patients Treated for Early-Stage Breast Cancer.
Clin Cancer Res
; 26(11): 2556-2564, 2020 06 01.
Article
em En
| MEDLINE
| ID: mdl-32170028
PURPOSE: 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. EXPERIMENTAL DESIGN: 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. RESULTS: 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 postoperative and 19% (n = 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). CONCLUSIONS: 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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
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Neoplasia Residual
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Receptor alfa de Estrogênio
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DNA Tumoral Circulante
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Recidiva Local de Neoplasia
Tipo de estudo:
Diagnostic_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Adult
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Female
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Humans
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article