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dc.contributor.authorStaaf, Johan
dc.contributor.authorRingnér, Markus
dc.contributor.authorVallon-Christersson, Johan
dc.contributor.authorJönsson, Göran
dc.contributor.authorBendahl, Pär-Ola
dc.contributor.authorHolm, Karolina
dc.contributor.authorArason, Adalgeir
dc.contributor.authorGunnarsson, Haukur
dc.contributor.authorHegardt, Cecilia
dc.contributor.authorAgnarsson, Bjarni A
dc.contributor.authorLuts, Lena
dc.contributor.authorGrabau, Dorthe
dc.contributor.authorFernö, Mårten
dc.contributor.authorMalmström, Per-Olof
dc.contributor.authorJohannsson, Oskar Th
dc.contributor.authorLoman, Niklas
dc.contributor.authorBarkardottir, Rosa B
dc.contributor.authorBorg, Ake
dc.date.accessioned2011-01-05T13:20:43Z
dc.date.available2011-01-05T13:20:43Z
dc.date.issued2010-04-10
dc.date.submitted2011-01-05
dc.identifier.citationJ. Clin. Oncol. 2010, 28(11):1813-20en
dc.identifier.issn1527-7755
dc.identifier.pmid20231686
dc.identifier.doi10.1200/JCO.2009.22.8775
dc.identifier.urihttp://hdl.handle.net/2336/118685
dc.descriptionTo access publisher full text version of this article. Please click on the hyperlink in Additional Links fielden
dc.description.abstractPURPOSE Human epidermal growth factor receptor 2 (HER2) gene amplification or protein overexpression (HER2 positivity) defines a clinically challenging subgroup of patients with breast cancer (BC) with variable prognosis and response to therapy. We aimed to investigate the heterogeneous biologic appearance and clinical behavior of HER2-positive tumors using molecular profiling. PATIENTS AND METHODS Hierarchical clustering of gene expression data from 58 HER2-amplified tumors of various stage, histologic grade, and estrogen receptor (ER) status was used to construct a HER2-derived prognostic predictor that was further evaluated in several large independent BC data sets. RESULTS Unsupervised analysis identified three subtypes of HER2-positive tumors with mixed stage, histologic grade, and ER status. One subtype had a significantly worse clinical outcome. A prognostic predictor was created based on differentially expressed genes between the subtype with worse outcome and the other subtypes. The predictor was able to define patient groups with better and worse outcome in HER2-positive BC across multiple independent BC data sets and identify a sizable HER2-positive group with long disease-free survival and low mortality. Significant correlation to prognosis was also observed in basal-like, ER-negative, lymph node-positive, and high-grade tumors, irrespective of HER2 status. The predictor included genes associated with immune response, tumor invasion, and metastasis. CONCLUSION The HER2-derived prognostic predictor provides further insight into the heterogeneous biology of HER2-positive tumors and may become useful for improved selection of patients who need additional treatment with new drugs targeting the HER2 pathway.
dc.language.isoenen
dc.publisherAmerican Society of Clinical Oncologyen
dc.relation.urlhttp://dx.doi.org/10.1200/JCO.2009.22.8775en
dc.subject.meshBreast Neoplasmsen
dc.subject.meshCarcinoma, Basal Cellen
dc.subject.meshFemaleen
dc.subject.meshGene Amplificationen
dc.subject.meshGene Expression Profilingen
dc.subject.meshHumansen
dc.subject.meshLymph Nodesen
dc.subject.meshMiddle Ageden
dc.subject.meshNeoplasm Stagingen
dc.subject.meshOligonucleotide Array Sequence Analysisen
dc.subject.meshPrognosisen
dc.subject.meshReceptor, erbB-2en
dc.subject.meshReceptors, Estrogenen
dc.subject.meshSurvival Rateen
dc.subject.meshTumor Markers, Biologicalen
dc.titleIdentification of subtypes in human epidermal growth factor receptor 2--positive breast cancer reveals a gene signature prognostic of outcomeen
dc.typeArticleen
dc.contributor.departmentDepartment of Oncology, CREATE Health Strategic Center for TranslationalCancer Research, Lund University, Lund, Sweden.en
dc.identifier.journalJournal of clinical oncology : official journal of the American Society of Clinical Oncologyen
html.description.abstractPURPOSE Human epidermal growth factor receptor 2 (HER2) gene amplification or protein overexpression (HER2 positivity) defines a clinically challenging subgroup of patients with breast cancer (BC) with variable prognosis and response to therapy. We aimed to investigate the heterogeneous biologic appearance and clinical behavior of HER2-positive tumors using molecular profiling. PATIENTS AND METHODS Hierarchical clustering of gene expression data from 58 HER2-amplified tumors of various stage, histologic grade, and estrogen receptor (ER) status was used to construct a HER2-derived prognostic predictor that was further evaluated in several large independent BC data sets. RESULTS Unsupervised analysis identified three subtypes of HER2-positive tumors with mixed stage, histologic grade, and ER status. One subtype had a significantly worse clinical outcome. A prognostic predictor was created based on differentially expressed genes between the subtype with worse outcome and the other subtypes. The predictor was able to define patient groups with better and worse outcome in HER2-positive BC across multiple independent BC data sets and identify a sizable HER2-positive group with long disease-free survival and low mortality. Significant correlation to prognosis was also observed in basal-like, ER-negative, lymph node-positive, and high-grade tumors, irrespective of HER2 status. The predictor included genes associated with immune response, tumor invasion, and metastasis. CONCLUSION The HER2-derived prognostic predictor provides further insight into the heterogeneous biology of HER2-positive tumors and may become useful for improved selection of patients who need additional treatment with new drugs targeting the HER2 pathway.


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