dc.contributor.author | Garcia-Murillas, I | |
dc.contributor.author | Schiavon, G | |
dc.contributor.author | Weigelt, B | |
dc.contributor.author | Ng, C | |
dc.contributor.author | Hrebien, S | |
dc.contributor.author | Cutts, RJ | |
dc.contributor.author | Cheang, M | |
dc.contributor.author | Osin, P | |
dc.contributor.author | Nerurkar, A | |
dc.contributor.author | Kozarewa, I | |
dc.contributor.author | Garrido, JA | |
dc.contributor.author | Dowsett, M | |
dc.contributor.author | Reis-Filho, JS | |
dc.contributor.author | Smith, IE | |
dc.contributor.author | Turner, NC | |
dc.date.accessioned | 2016-10-31T12:01:33Z | |
dc.date.issued | 2015-08-26 | |
dc.identifier.citation | Science translational medicine, 2015, 7 (302), pp. 302ra133 - ? | |
dc.identifier.issn | 1946-6234 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/194 | |
dc.identifier.eissn | 1946-6242 | |
dc.identifier.doi | 10.1126/scitranslmed.aab0021 | |
dc.description.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. | |
dc.format | Print | |
dc.format.extent | 302ra133 - ? | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | AMER ASSOC ADVANCEMENT SCIENCE | |
dc.subject | Humans | |
dc.subject | Breast Neoplasms | |
dc.subject | Neoplasm, Residual | |
dc.subject | Recurrence | |
dc.subject | DNA, Neoplasm | |
dc.subject | Mutation | |
dc.subject | Female | |
dc.subject | High-Throughput Nucleotide Sequencing | |
dc.subject | Precision Medicine | |
dc.title | Mutation tracking in circulating tumor DNA predicts relapse in early breast cancer. | |
dc.type | Journal Article | |
rioxxterms.versionofrecord | 10.1126/scitranslmed.aab0021 | |
rioxxterms.licenseref.startdate | 2015-08 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Science translational medicine | |
pubs.issue | 302 | |
pubs.notes | No embargo | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Breast Cancer Research | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Breast Cancer Research/Endocrinology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Breast Cancer Research/Molecular Oncology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Genomic Analysis – Clinical Trials | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Medicine (RMH Smith Cunningham) | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Medicine (RMH Smith Cunningham)/Medicine (RMH Smith Cunningham) (hon.) | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology/Endocrinology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology/Endocrinology/Endocrinology (hon.) | |
pubs.organisational-group | /ICR/Primary Group/Royal Marsden Clinical Units | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Breast Cancer Research | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Breast Cancer Research/Endocrinology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Breast Cancer Research/Molecular Oncology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Genomic Analysis – Clinical Trials | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Medicine (RMH Smith Cunningham) | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Medicine (RMH Smith Cunningham)/Medicine (RMH Smith Cunningham) (hon.) | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology/Endocrinology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology/Endocrinology/Endocrinology (hon.) | |
pubs.organisational-group | /ICR/Primary Group/Royal Marsden Clinical Units | |
pubs.publication-status | Published | |
pubs.volume | 7 | |
pubs.embargo.terms | No embargo | |
icr.researchteam | Molecular Oncology | |
icr.researchteam | Genomic Analysis – Clinical Trials | |
icr.researchteam | Medicine (RMH Smith Cunningham) | |
icr.researchteam | Endocrinology | |
dc.contributor.icrauthor | Garcia-Murillas, Isaac | |
dc.contributor.icrauthor | Cutts, Rosalind | |
dc.contributor.icrauthor | Cheang, Chon | |
dc.contributor.icrauthor | Turner, Nicholas | |