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dc.contributor.authorWillis, S
dc.contributor.authorPolydoropoulou, V
dc.contributor.authorSun, Y
dc.contributor.authorYoung, B
dc.contributor.authorTsourti, Z
dc.contributor.authorKarlis, D
dc.contributor.authorLong, B
dc.contributor.authorLin, X
dc.contributor.authorTheel, S
dc.contributor.authorCarlson, J
dc.contributor.authorGyőrffy, B
dc.contributor.authorWilliams, C
dc.contributor.authorAbramovitz, M
dc.contributor.authorDafni, U
dc.contributor.authorDowsett, M
dc.contributor.authorLeyland-Jones, B
dc.date.accessioned2020-08-18T15:43:11Z
dc.date.issued2018-01
dc.identifier.citationJCO precision oncology, 2018, 2
dc.identifier.issn2473-4284
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3982
dc.identifier.eissn2473-4284
dc.identifier.doi10.1200/po.18.00016
dc.description.abstractPurpose The Herceptin Adjuvant study is an international multicenter randomized trial that compared 1 or 2 years of trastuzumab given every 3 weeks with observation in women with human epidermal growth factor 2-positive (HER2+) breast cancer after chemotherapy. Identification of biomarkers predictive of a benefit from trastuzumab will minimize overtreatment and lower health care costs.Methods To identify possible single-gene biomarkers, an exploratory analysis of 3,669 gene probes not expected to be expressed in normal breast tissue was conducted. Disease-free survival (DFS) was used as the end point in a Cox regression model, with the interaction term between C8A mRNA and treatment as a categorical variable split on the cohort mean.Results A significant interaction between C8A mRNA and treatment was detected ( P < .001), indicating a predictive response to trastuzumab treatment. For the C8A-low subgroup (mRNA expression lower than the cohort mean), no significant treatment benefit was observed ( P = .73). In the C8A-high subgroup, patients receiving trastuzumab experienced a lower hazard of a DFS event by approximately 75% compared with those in the observation arm (hazard ratio [HR], 0.25; P < .001). A significant prognostic effect of C8A mRNA also was seen ( P < .001) in the observation arm, where the C8A-high group hazard of a DFS event was three times the respective hazard of the C8A-low group (HR, 3.27; P < .001). C8A mRNA is highly prognostic in the Hungarian Academy of Science HER2+ gastric cancer cohort (HR, 1.72; P < .001).Conclusion C8A as a single-gene biomarker prognostic of DFS and predictive of a benefit from trastuzumab has the potential to improve the standard of care in HER2+ breast cancer if validated by additional studies. Understanding the advantage of overexpression of C8A related to the innate immune response can give insight into the mechanisms that drive cancer.
dc.formatElectronic-eCollection
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleExploratory Analysis of Single-Gene Predictive Biomarkers in HERA DASL Cohort Reveals That C8A mRNA Expression Is Prognostic of Outcome and Predictive of Benefit of Trastuzumab.
dc.typeJournal Article
dcterms.dateAccepted2018-07-03
rioxxterms.versionofrecord10.1200/po.18.00016
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2018-01
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfJCO precision oncology
pubs.notesNo 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/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
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/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.publication-statusPublished
pubs.volume2
pubs.embargo.termsNo embargo
icr.researchteamEndocrinologyen_US
dc.contributor.icrauthorDowsett, Mitchen


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