| _version_ |
1826194425844334592
|
| collection |
MIT
|
| description |
© 2020 American Association for Cancer Research. 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.
|
| first_indexed |
2024-09-23T09:55:36Z
|
| format |
Article
|
| id |
mit-1721.1/134635
|
| institution |
Massachusetts Institute of Technology
|
| language |
English
|
| last_indexed |
2024-09-23T09:55:36Z
|
| publishDate |
2021
|
| publisher |
American Association for Cancer Research (AACR)
|
| record_format |
dspace
|
| spelling |
mit-1721.1/1346352021-10-28T04:38:11Z Sensitive Detection of Minimal Residual Disease in Patients Treated for Early-Stage Breast Cancer © 2020 American Association for Cancer Research. 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. 2021-10-27T20:05:54Z 2021-10-27T20:05:54Z 2020 2021-06-14T15:32:13Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/134635 en 10.1158/1078-0432.CCR-19-3005 Clinical Cancer Research Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf American Association for Cancer Research (AACR) PMC
|
| spellingShingle |
Sensitive Detection of Minimal Residual Disease in Patients Treated for Early-Stage Breast Cancer
|
| title |
Sensitive Detection of Minimal Residual Disease in Patients Treated for Early-Stage Breast Cancer
|
| title_full |
Sensitive Detection of Minimal Residual Disease in Patients Treated for Early-Stage Breast Cancer
|
| title_fullStr |
Sensitive Detection of Minimal Residual Disease in Patients Treated for Early-Stage Breast Cancer
|
| title_full_unstemmed |
Sensitive Detection of Minimal Residual Disease in Patients Treated for Early-Stage Breast Cancer
|
| title_short |
Sensitive Detection of Minimal Residual Disease in Patients Treated for Early-Stage Breast Cancer
|
| title_sort |
sensitive detection of minimal residual disease in patients treated for early stage breast cancer
|
| url |
https://hdl.handle.net/1721.1/134635
|