dc.contributor.author | Filipits, M | |
dc.contributor.author | Dafni, U | |
dc.contributor.author | Gnant, M | |
dc.contributor.author | Polydoropoulou, V | |
dc.contributor.author | Hills, M | |
dc.contributor.author | Kiermaier, A | |
dc.contributor.author | de Azambuja, E | |
dc.contributor.author | Larsimont, D | |
dc.contributor.author | Rojo, F | |
dc.contributor.author | Viale, G | |
dc.contributor.author | Toi, M | |
dc.contributor.author | Harbeck, N | |
dc.contributor.author | Prichard, KI | |
dc.contributor.author | Gelber, RD | |
dc.contributor.author | Dinh, P | |
dc.contributor.author | Zardavas, D | |
dc.contributor.author | Leyland-Jones, B | |
dc.contributor.author | Piccart-Gebhart, MJ | |
dc.contributor.author | Dowsett, M | |
dc.contributor.author | TransHERA investigators | |
dc.date.accessioned | 2018-08-09T10:34:39Z | |
dc.date.issued | 2018-07 | |
dc.identifier.citation | Clinical cancer research : an official journal of the American Association for Cancer Research, 2018, 24 (13), pp. 3079 - 3086 | |
dc.identifier.issn | 1078-0432 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/2310 | |
dc.identifier.eissn | 1557-3265 | |
dc.identifier.doi | 10.1158/1078-0432.ccr-17-3473 | |
dc.description.abstract | Purpose: 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.format | Print-Electronic | |
dc.format.extent | 3079 - 3086 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.rights.uri | https://www.rioxx.net/licenses/under-embargo-all-rights-reserved | |
dc.subject | TransHERA investigators | |
dc.subject | Humans | |
dc.subject | Breast Neoplasms | |
dc.subject | Neoplasm Metastasis | |
dc.subject | Receptor, erbB-2 | |
dc.subject | Cyclin D1 | |
dc.subject | Neoplasm Staging | |
dc.subject | Prognosis | |
dc.subject | Treatment Outcome | |
dc.subject | Chemotherapy, Adjuvant | |
dc.subject | Gene Expression Regulation, Neoplastic | |
dc.subject | Adult | |
dc.subject | Aged | |
dc.subject | Middle Aged | |
dc.subject | Female | |
dc.subject | Cyclin-Dependent Kinase Inhibitor p27 | |
dc.subject | Young Adult | |
dc.subject | Neoplasm Grading | |
dc.subject | Biomarkers, Tumor | |
dc.subject | Trastuzumab | |
dc.subject | Antineoplastic Agents, Immunological | |
dc.title | Association of p27 and Cyclin D1 Expression and Benefit from Adjuvant Trastuzumab Treatment in HER2-Positive Early Breast Cancer: A TransHERA Study. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2018-03-06 | |
rioxxterms.versionofrecord | 10.1158/1078-0432.ccr-17-3473 | |
rioxxterms.licenseref.uri | https://www.rioxx.net/licenses/under-embargo-all-rights-reserved | |
rioxxterms.licenseref.startdate | 2018-07 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Clinical cancer research : an official journal of the American Association for Cancer Research | |
pubs.issue | 13 | |
pubs.notes | Not 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-status | Published | |
pubs.volume | 24 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Endocrinology | |
dc.contributor.icrauthor | Dowsett, Mitch | |