dc.contributor.author | Willis, S | |
dc.contributor.author | Polydoropoulou, V | |
dc.contributor.author | Sun, Y | |
dc.contributor.author | Young, B | |
dc.contributor.author | Tsourti, Z | |
dc.contributor.author | Karlis, D | |
dc.contributor.author | Long, B | |
dc.contributor.author | Lin, X | |
dc.contributor.author | Theel, S | |
dc.contributor.author | Carlson, J | |
dc.contributor.author | Győrffy, B | |
dc.contributor.author | Williams, C | |
dc.contributor.author | Abramovitz, M | |
dc.contributor.author | Dafni, U | |
dc.contributor.author | Dowsett, M | |
dc.contributor.author | Leyland-Jones, B | |
dc.date.accessioned | 2020-08-18T15:43:11Z | |
dc.date.issued | 2018-01 | |
dc.identifier.citation | JCO precision oncology, 2018, 2 | |
dc.identifier.issn | 2473-4284 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/3982 | |
dc.identifier.eissn | 2473-4284 | |
dc.identifier.doi | 10.1200/po.18.00016 | |
dc.description.abstract | Purpose 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.format | Electronic-eCollection | |
dc.language | eng | |
dc.language.iso | eng | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.title | Exploratory 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.type | Journal Article | |
dcterms.dateAccepted | 2018-07-03 | |
rioxxterms.versionofrecord | 10.1200/po.18.00016 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2018-01 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | JCO precision oncology | |
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/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-status | Published | |
pubs.volume | 2 | |
pubs.embargo.terms | No embargo | |
icr.researchteam | Endocrinology | en_US |
dc.contributor.icrauthor | Dowsett, Mitch | |