Publications Repository

Publications Repository

View Item 
  •   Home
  • ICR Divisions
  • Breast Cancer Research
  • View Item
  • Home
  • ICR Divisions
  • Breast Cancer Research
  • View Item
JavaScript is disabled for your browser. Some features of this site may not work without it.

Mutation tracking in circulating tumor DNA predicts relapse in early breast cancer.

Thumbnail
View/Open
Accepted version (5.521Mb)
Publication Date
2015-08
ICR Author
Garcia-Murillas, Isaac
Turner, Nicholas
Dowsett, Mitch
Smith, Ian
Cheang, Chon
Author
Garcia-Murillas, I
Schiavon, G
Weigelt, B
Ng, C
Hrebien, S
Cutts, RJ
Cheang, M
Osin, P
Nerurkar, A
Kozarewa, I
Garrido, JA
Dowsett, M
Reis-Filho, JS
Smith, IE
Turner, NC
Type
Journal Article
Metadata
Show full item record
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.
URL
https://repository.icr.ac.uk/handle/internal/194
Collections
  • Breast Cancer Research
  • Clinical Studies
  • Molecular Pathology
Version of record
10.1126/scitranslmed.aab0021
Subject
Humans
Breast Neoplasms
Neoplasm, Residual
Recurrence
DNA, Neoplasm
Mutation
Female
High-Throughput Nucleotide Sequencing
Precision Medicine
Research team
Molecular Oncology
Genomic Analysis – Clinical Trials
Medicine (RMH Smith Cunningham)
Endocrinology
Language
eng
License start date
2015-08
Citation
Science translational medicine, 2015, 7 (302), pp. 302ra133 - ?

Browse

All of ICR repositoryICR Divisions & RM Clinical UnitsIssue dateAuthorsTitlesSubjectsThis collectionIssue dateAuthorsTitlesSubjects

Statistics

Most popular itemsStatistics by countryMost popular authors
  • Login
  • Registered office: The Institute of Cancer Research, 123 Old Brompton Road, London, SW7 3RP
    A Charity, Not for Profit. Company Limited by Guarantee.
    Registered in England No. 534147. VAT Registration No. GB 849 0581 02.