dc.contributor.author | Schiavon, G | |
dc.contributor.author | Hrebien, S | |
dc.contributor.author | Garcia-Murillas, I | |
dc.contributor.author | Cutts, RJ | |
dc.contributor.author | Pearson, A | |
dc.contributor.author | Tarazona, N | |
dc.contributor.author | Fenwick, K | |
dc.contributor.author | Kozarewa, I | |
dc.contributor.author | Lopez-Knowles, E | |
dc.contributor.author | Ribas, R | |
dc.contributor.author | Nerurkar, A | |
dc.contributor.author | Osin, P | |
dc.contributor.author | Chandarlapaty, S | |
dc.contributor.author | Martin, L-A | |
dc.contributor.author | Dowsett, M | |
dc.contributor.author | Smith, IE | |
dc.contributor.author | Turner, NC | |
dc.coverage.spatial | United States | |
dc.date.accessioned | 2022-08-16T13:37:10Z | |
dc.date.available | 2022-08-16T13:37:10Z | |
dc.date.issued | 2015-11-11 | |
dc.identifier | ARTN 313ra182 | |
dc.identifier | 7/313/313ra182 | |
dc.identifier.citation | Science Translational Medicine, 2015, 7 (313), pp. 313ra182 - | |
dc.identifier.issn | 1946-6234 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/5275 | |
dc.identifier.eissn | 1946-6242 | |
dc.identifier.eissn | 1946-6242 | |
dc.identifier.doi | 10.1126/scitranslmed.aac7551 | |
dc.description.abstract | Acquired ESR1 mutations are a major mechanism of resistance to aromatase inhibitors (AIs). We developed ultra high-sensitivity multiplex digital polymerase chain reaction assays for ESR1 mutations in circulating tumor DNA (ctDNA) and investigated the clinical relevance and origin of ESR1 mutations in 171 women with advanced breast cancer. ESR1 mutation status in ctDNA showed high concordance with contemporaneous tumor biopsies and was accurately assessed in samples shipped at room temperature in preservative tubes. ESR1 mutations were found exclusively in estrogen receptor-positive breast cancer patients previously exposed to AI. Patients with ESR1 mutations had a substantially shorter progression-free survival on subsequent AI-based therapy [hazard ratio, 3.1; 95% confidence interval (CI), 1.9 to 23.1; P = 0.0041]. ESR1 mutation prevalence differed markedly between patients who were first exposed to AI during the adjuvant and metastatic settings [5.8% (3 of 52) versus 36.4% (16 of 44), respectively; P = 0.0002]. In an independent cohort, ESR1 mutations were identified in 0% (0 of 32; 95% CI, 0 to 10.9) tumor biopsies taken after progression on adjuvant AI. In a patient with serial sampling, ESR1 mutation was selected during metastatic AI therapy to become the dominant clone in the cancer. ESR1 mutations can be robustly identified with ctDNA analysis and predict for resistance to subsequent AI therapy. ESR1 mutations are rarely acquired during adjuvant AI but are commonly selected by therapy for metastatic disease, providing evidence that mechanisms of resistance to targeted therapy may be substantially different between the treatment of micrometastatic and overt metastatic cancer. | |
dc.format | Print | |
dc.format.extent | 313ra182 - | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | AMER ASSOC ADVANCEMENT SCIENCE | |
dc.relation.ispartof | Science Translational Medicine | |
dc.rights.uri | http://www.rioxx.net/licenses/all-rights-reserved | |
dc.subject | Antineoplastic Agents | |
dc.subject | Aromatase Inhibitors | |
dc.subject | Breast Neoplasms | |
dc.subject | Estrogen Receptor alpha | |
dc.subject | Female | |
dc.subject | Humans | |
dc.subject | Multiplex Polymerase Chain Reaction | |
dc.title | Analysis of ESR1 mutation in circulating tumor DNA demonstrates evolution during therapy for metastatic breast cancer. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2015-11-11 | |
dc.date.updated | 2022-08-16T13:12:51Z | |
rioxxterms.version | AM | |
rioxxterms.versionofrecord | 10.1126/scitranslmed.aac7551 | |
rioxxterms.licenseref.startdate | 2015-11-11 | |
rioxxterms.type | Journal Article/Review | |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/26560360 | |
pubs.issue | 313 | |
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/Molecular Oncology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Clinical Trials & Statistics Unit | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Medicine (RMH Smith Cunningham) | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Closed research teams | |
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/Royal Marsden Clinical Units | |
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/Endocrinology/Endocrinology (hon.) | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Closed research teams/Endocrinology | |
pubs.publication-status | Published | |
pubs.volume | 7 | |
icr.researchteam | Molecular Oncology | |
icr.researchteam | Endocrinology | |
icr.researchteam | Medicine (RMH) | |
dc.contributor.icrauthor | Garcia-Murillas, Isaac | |
dc.contributor.icrauthor | Cutts, Rosalind | |
dc.contributor.icrauthor | Pearson, Alex | |
dc.contributor.icrauthor | Lopez Knowles, Elena | |
dc.contributor.icrauthor | Martin, Lesley-Ann | |
dc.contributor.icrauthor | Turner, Nicholas | |
icr.provenance | Deposited by Dr Elena Lopez Knowles on 2022-08-16. Deposit type is initial. No. of files: 1. Files: scitranslmed.aac7551.pdf | |
icr.provenance | Deposited by Mr Arek Surman (impersonating Dr Elena Lopez Knowles) on 2022-08-16. Deposit type is subsequent. No. of files: 1. Files: nihms-803731 (1).pdf | |