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dc.contributor.authorFilipits, M
dc.contributor.authorDafni, U
dc.contributor.authorGnant, M
dc.contributor.authorPolydoropoulou, V
dc.contributor.authorHills, M
dc.contributor.authorKiermaier, A
dc.contributor.authorde Azambuja, E
dc.contributor.authorLarsimont, D
dc.contributor.authorRojo, F
dc.contributor.authorViale, G
dc.contributor.authorToi, M
dc.contributor.authorHarbeck, N
dc.contributor.authorPrichard, KI
dc.contributor.authorGelber, RD
dc.contributor.authorDinh, P
dc.contributor.authorZardavas, D
dc.contributor.authorLeyland-Jones, B
dc.contributor.authorPiccart-Gebhart, MJ
dc.contributor.authorDowsett, M
dc.contributor.authorTransHERA investigators
dc.date.accessioned2018-08-09T10:34:39Z
dc.date.issued2018-07
dc.identifier.citationClinical cancer research : an official journal of the American Association for Cancer Research, 2018, 24 (13), pp. 3079 - 3086
dc.identifier.issn1078-0432
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/2310
dc.identifier.eissn1557-3265
dc.identifier.doi10.1158/1078-0432.ccr-17-3473
dc.description.abstractPurpose: To assess the prognostic and predictive value of selected biomarkers involved in cell-cycle regulation or proliferation in patients with HER2-positive early breast cancer.Experimental Design: Protein expression of TOP2A, Ki67, cyclin D1, and p27 was immunohistochemically determined in tissue microarrays of surgical specimens from 862 patients randomized to trastuzumab (1 or 2 years; N = 561) and observation (N = 301) arms of the HERA trial. The primary analysis endpoint was disease-free survival (DFS). Biomarkers were examined as continuous or categorical variables (predefined cutoffs). Interaction terms between biomarkers and treatment were assessed in multivariate Cox models adjusted for variables of clinical interest.Results: A significant interaction was detected between p27 and treatment (adjusted P = 0.0049). Trastuzumab effect was significant in the p27-low subgroup (≤70% p27-positive tumor cells; N = 318). HR Comb Trast vs. Obs 0.44, 95% CI, 0.29-0.65 (P < 0.001). No trastuzumab effect was observed in the p27-high subgroup N = 435; HR Comb Trast vs. Obs 0.97, 95% CI, 0.66-1.44, P = 0.89), indicating that these patients derived little or no benefit from trastuzumab treatment. A prognostic effect of p27 on DFS was observed, with p27-high patients experiencing half the hazard of a DFS event compared with low ones (HR p27 High vs. Low 0.49, 95% CI, 0.32-0.75). TOP2A, Ki67, and cyclin D1, as categorical variables were not predictive, whereas cyclin D1 as continuous variable was predictive of trastuzumab benefit.Conclusions: In TransHERA, patients with HER2-positive early breast cancer with low p27 expression in their tumors benefited from trastuzumab treatment, whereas patients with high p27 expression did not. Clin Cancer Res; 24(13); 3079-86. ©2018 AACR.
dc.formatPrint-Electronic
dc.format.extent3079 - 3086
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://www.rioxx.net/licenses/under-embargo-all-rights-reserved
dc.subjectTransHERA investigators
dc.subjectHumans
dc.subjectBreast Neoplasms
dc.subjectNeoplasm Metastasis
dc.subjectReceptor, erbB-2
dc.subjectCyclin D1
dc.subjectNeoplasm Staging
dc.subjectPrognosis
dc.subjectTreatment Outcome
dc.subjectChemotherapy, Adjuvant
dc.subjectGene Expression Regulation, Neoplastic
dc.subjectAdult
dc.subjectAged
dc.subjectMiddle Aged
dc.subjectFemale
dc.subjectCyclin-Dependent Kinase Inhibitor p27
dc.subjectYoung Adult
dc.subjectNeoplasm Grading
dc.subjectBiomarkers, Tumor
dc.subjectTrastuzumab
dc.subjectAntineoplastic Agents, Immunological
dc.titleAssociation of p27 and Cyclin D1 Expression and Benefit from Adjuvant Trastuzumab Treatment in HER2-Positive Early Breast Cancer: A TransHERA Study.
dc.typeJournal Article
dcterms.dateAccepted2018-03-06
rioxxterms.versionofrecord10.1158/1078-0432.ccr-17-3473
rioxxterms.licenseref.urihttps://www.rioxx.net/licenses/under-embargo-all-rights-reserved
rioxxterms.licenseref.startdate2018-07
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfClinical cancer research : an official journal of the American Association for Cancer Research
pubs.issue13
pubs.notesNot known
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.volume24
pubs.embargo.termsNot known
icr.researchteamEndocrinologyen_US
dc.contributor.icrauthorDowsett, Mitchen


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