Mutation tracking in circulating tumor DNA predicts relapse in early breast cancer Journal Article
| Authors: | Garcia-Murillas, I.; Schiavon, G.; Weigelt, B.; Ng, C.; Hrebien, S.; Cutts, R. J.; Cheang, M.; Osin, P.; Nerurkar, A.; Kozarewa, I.; Garrido, J. A.; Dowsett, M.; Reis-Filho, J. S.; Smith, I. E.; Turner, N. C. |
| Article Title: | Mutation tracking in circulating tumor DNA predicts relapse in early breast cancer |
| Abstract: | The identification of early-stage breast cancer patients at high risk of relapse would allow tailoring of adjuvant therapy approaches. We assessed whether analysis of circulating tumor DNA (ctDNA) in plasma can be used to monitor for minimal residual disease (MRD) in breast cancer. In a prospective cohort of 55 early breast cancer patients receiving neoadjuvant chemotherapy, detection of ctDNA in plasma after completion of apparently curative treatment - either at a single postsurgical time point or with serial follow-up plasma samples - predicted metastatic relapse with high accuracy [hazard ratio, 25.1 (confidence interval, 4.08 to 130.5; log-rank P < 0.0001) or 12.0 (confidence interval, 3.36 to 43.07; log-rank P < 0.0001), respectively]. Mutation tracking in serial samples increased sensitivity for the prediction of relapse, with a median lead time of 7.9 months over clinical relapse. We further demonstrated that targeted capture sequencing analysis of ctDNA could define the genetic events of MRD, and that MRD sequencing predicted the genetic events of the subsequent metastatic relapse more accurately than sequencing of the primary cancer. Mutation tracking can therefore identify early breast cancer patients at high risk of relapse. Subsequent adjuvant therapeutic interventions could be tailored to the genetic events present in the MRD, a therapeutic approach that could in part combat the challenge posed by intratumor genetic heterogeneity. © 2015, American Association for the Advancement of Science. All rights reserved. |
| Keywords: | controlled study; primary tumor; unclassified drug; major clinical study; sequence analysis; cancer recurrence; cancer adjuvant therapy; follow up; prospective study; polymerase chain reaction; sensitivity analysis; breast cancer; cohort analysis; mutational analysis; prediction; genome analysis; dna; blood sampling; minimal residual disease; early cancer; dna sequence; dna determination; measurement accuracy; human; female; priority journal; article; circulating tumor dna; mutation tracking |
| Journal Title: | Science Translational Medicine |
| Volume: | 7 |
| Issue: | 302 |
| ISSN: | 1946-6234 |
| Publisher: | American Association for the Advancement of Science |
| Date Published: | 2015-08-26 |
| Start Page: | 302ra133 |
| Language: | English |
| DOI: | 10.1126/scitranslmed.aab0021 |
| PROVIDER: | scopus |
| PUBMED: | 26311728 |
| DOI/URL: | |
| Notes: | Export Date: 2 October 2015 -- Source: Scopus |
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