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Gene profiling of HER2 breast cancer patients treated with adjuvant trastuzumab

ABSTRACT: The human epidermal growth factor receptor 2 (HER2) gene encodes a tyrosine kinase receptor that controls important signal transduction pathways in breast cancer. Amplification and overexpression of the HER2 gene occurs in approximately 20% of breast cancers and is associated with an aggressive clinical phenotype. Trastuzumab, a humanized monoclonal antibody that targets HER2 showed exceptional efficacy in the treatment of breast cancer. In the adjuvant treatment of breast cancer patients, five randomized trials showed significant benefit of trastuzumab, with a reduction in the rate of recurrence of approximately 50% and improvement in the rate of survival of approximately 30%. In the current study, positive early stage breast cancer samples treated with adjuvant trastuzumab provided by institute Jules Bordet (IJB) and KUL. Gene expression and clinical outcome data were available. to better understand the genetic regulations and effects of the trastuzumab, we profile the the genes expression of positive early stage breast cancer samples treated with adjuvant trastuzumab.

ORGANISM(S): Homo sapiens

PROVIDER: GSE58984 | GEO | 2016/12/31

SECONDARY ACCESSION(S): PRJNA254048

REPOSITORIES: GEO

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Project description:To assess pathologic complete response (pCR), clinical response, feasibility, safety, and potential predictors of response to preoperative trastuzumab plus vinorelbine in patients with operable, human epidermal growth factor receptor 2 (HER2)-positive breast cancer. EXPERIMENTAL DESIGN: 48 patients received preoperative trastuzumab and vinorelbine weekly for 12 weeks. Single and multigene biomarker studies were done in an attempt to identify predictors of response. RESULTS: 8 of 40 (20%) patients achieved pCR (95% confidence interval, 9-36%). Of 9 additional patients recruited for protocol-defined toxicity analysis, 8 were evaluable; 42 of 48 (88%) patients had clinical response (16 patients, clinical complete response; 26 patients, clinical partial response). T(1) tumors more frequently exhibited clinical complete response (P = 0.05) and showed a trend to exhibit pCR (P = 0.07). 5 (13%) patients experienced grade 1 cardiac dysfunction during preoperative treatment. Neither HER2 nor estrogen receptor status changed significantly after exposure to trastuzumab and vinorelbine. RNA profiling identified three top-level clusters by unsupervised analysis. Tumors with extremes of response [pCR (n = 3) versus nonresponse (n = 3)] fell into separate groups by hierarchical clustering. No predictive genes were identified in pCR tumors. Nonresponding tumors were more likely to be T(4) stage (P = 0.02) and express basal markers (P < 0.00001), growth factors, and growth factor receptors. Insulin-like growth factor-I receptor membrane expression was associated with a lower response rate (50% vs 97%; P = 0.001). CONCLUSIONS: Preoperative trastuzumab plus vinorelbine is active and well tolerated in patients with HER2-positive, operable, stage II/III breast cancer. HER2-overexpressing tumors with a basal-like phenotype, or with expression of insulin-like growth factor-I receptor and other proteins involved in growth factor pathways, are more likely to be resistant to this regimen. harri-00137 Assay Type: Gene Expression Provider: Affymetrix Array Designs: HG-U133_Plus_2 Organism: Homo sapiens (ncbitax)