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  • Head-to-head comparison of the 70-gene signature versus the 21-gene assay: cost-effectiveness and the effect of compliance | Agendia
    early breast cancer Although the results of ongoing prospective trials will only become available in some years the tests have already been included in clinical guidelines such as St Gallen s In literature the cost effectiveness CE of both tests as compared to conventional prognostic tests has been described We report on a direct comparison of CE as different compliance rates were reported we also taken these into account A Markov decision model with a time horizon of 20 years was developed to assess the effects costs and CE of three alternatives 21 gene 70 gene and St Gallen SG or Adjuvant Online AO dependent on the dataset used in patients with early node negative breast cancer Sensitivity and specificity were based on two datasets incorporating compliances rates based on literature For both datasets whereas the 70 gene signature yielded more quality adjusted life years QALYs and was less costly the 21 gene amounted more life years LYs but was more costly The decision uncertainty surrounding the probability of CE of the Thomassen series amounted 55 for both cost LY and cost QALY for the Fan series 80 for LY and 65 for QALYs Taking reported compliance with discordant test results into account in general the effect of all strategies decreased while the costs increased without relatively influencing the CEA performance This comparison indicates that the performances of the 70 gene and the 21 gene based on reported studies are close The 21 gene has the highest probability of being cost effective when focusing on cost LY while focusing on cost QALY the 70 gene signature was most cost effective The level of compliance can have serious impact on the CE With additional data preferably from head to head outcome studies and especially on compliance concerning discordant test results calculations

    Original URL path: http://www.agendia.com/head-to-head-comparison-of-the-70-gene-signature-versus-the-21-gene-assay-cost-effectiveness-and-the-effect-of-compliance/ (2016-05-01)
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  • First generation prognostic gene signatures for breast cancer predict both survival and chemotherapy sensitivity and identify overlapping patient populations | Agendia
    clinical variables and six previously described prognostic signatures on 228 tumors from patients who received homogeneous preoperative chemotherapy and had long term follow up information for survival We used the area under the receiver operator characteristic curve AUC to compare predictors and also performed univariate and multivariate analyses including the genomic and clinical variables and plotted Kaplan Meir survival curves All genomic prognostic markers had statistically similar AUCs and sensitivity to predict 5 year progression free survival PFS sensitivities ranged from 0 591 to 0 773 and AUCs 0 599 0 673 overall survival OS sensitivities 0 590 0 769 AUCs 0 596 0 684 and pathologic complete response pCR sensitivities 0 596 0 851 AUCs 0 614 0 805 In multivariate analysis the genomic markers were not independent from one another however estrogen receptor Odds Ratio OR 7 63 P 0 001 and HER2 status OR 0 37 P 0 021 showed significant independent predictive values for pCR Nodal status remained an independent prognostic but not predictive variable OR for PFS 2 77 P 0 021 OR for OS 3 62 P 0 01 There was moderate to good agreement between different prediction results in pair wise comparisons First

    Original URL path: http://www.agendia.com/first-generation-prognostic-gene-signatures-for-breast-cancer-predict-both-survival-and-chemotherapy-sensitivity-and-identify-overlapping-patient-populations/ (2016-05-01)
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  • A diagnostic gene profile for molecular subtyping of breast cancer associated with treatment response | Agendia
    similar histopathological features can have strikingly different clinical outcomes Herein we report the development of a molecular subtyping profile BluePrint that enables rationalization in patient selection for either chemotherapy or endocrine therapy prescription An 80 Gene Molecular Subtyping Profile BluePrint was developed using 200 breast cancer patient specimens and confirmed on four independent validation cohorts n 784 Additionally the profile was tested as a predictor of chemotherapy response in 133 breast cancer patients treated with T FAC neoadjuvant chemotherapy BluePrint classification of a patient cohort that was treated with neoadjuvant chemotherapy n 133 shows improved distribution of pathological Complete Response pCR among molecular subgroups compared with local pathology 56 of the patients had a pCR in the Basal type subgroup 3 in the MammaPrint Low risk Luminal type subgroup 11 in the MammaPrint Highrisk Luminal type subgroup and 50 in the HER2 type subgroup The group of genes identifying Luminal type breast cancer is highly enriched for genes having an Estrogen Receptor binding site proximal to the promoterregion suggesting that these genes are direct targets of the Estrogen Receptor Implementation of this profile may improve the clinical management of breast cancer patients by enabling the selection of patients who are

    Original URL path: http://www.agendia.com/a-diagnostic-gene-profile-for-molecular-subtyping-of-breast-cancer-associated-with-treatment-response/ (2016-05-01)
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  • Strategies for subtypes-dealing with the diversity of breast cancer: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2011 | Agendia
    Coates R D Gelber B Thu rlimann H J Senn Panel May 23 2011 The 12th St Gallen International Breast Cancer Conference 2011 Expert Panel adopted a new approach to the classification of patients for therapeutic purposes based on the recognition of intrinsic biological subtypes within the breast cancer spectrum For practical purposes these subtypes may be approximated using clinicopathological rather than gene expression array criteria In general systemic therapy recommendations follow the subtype classification Thus Luminal A disease generally requires only endocrine therapy which also forms part of the treatment of the Luminal B subtype Chemotherapy is considered indicated for most patients with Luminal B Human Epidermal growth factor Receptor 2 HER2 positive and Triple negative ductal disease with the addition of trastuzumab in HER2 positive disease Progress was also noted in defining better tolerated local therapies in selected cases without loss of efficacy such as accelerated radiation therapy and the omission of axillary dissection under defined circumstances Broad treatment recommendations are presented recognizing that detailed treatment decisions need to consider disease extent host factors patient preferences and social and economic constraints See article Categories Abstract Poster 18 Accreditation 1 BluePrint 9 Clinical Studies 8 ColoPrint 5 Cost Effectiveness

    Original URL path: http://www.agendia.com/strategies-for-subtypes-dealing-with-the-diversity-of-breast-cancer-highlights-of-the-st-gallen-international-expert-consensus-on-the-primary-therapy-of-early-breast-cancer-2011/ (2016-05-01)
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  • Gene Expression Profiles from Formalin Fixed Paraffin Embedded Breast Cancer Tissue Are Largely Comparable to Fresh Frozen Matched Tissue | Agendia
    Van t Veer February 1 2011 Background and Methods Formalin Fixed Paraffin Embedded FFPE samples represent a valuable resource for cancer research However the discovery and development of new cancer biomarkers often requires fresh frozen FF samples Recently the Whole Genome WG DASL cDNA mediated Annealing Selection extension and Ligation assay was specifically developed to profile FFPE tissue However a thorough comparison of data generated from FFPE RNA and Fresh Frozen FF RNA using this platform is lacking To this end we profiled in duplicate 20 FFPE tissues and 20 matched FF tissues and evaluated the concordance of the DASL results from FFPE and matched FF material Methodology and Principal Findings We show that after proper normalization all FFPE and FF pairs exhibit a high level of similarity Pearson correlation 0 7 significantly larger than the similarity between non paired samples Interestingly the probes showing the highest correlation had a higher percentage G C content and were enriched for cell cycle genes Predictions of gene expression signatures developed on frozen material Intrinsic subtype Genomic Grade Index 70 gene signature showed a high level of concordance between FFPE and FF matched pairs Interestingly predictions based on a 60 gene DASL list best match with the 70 gene signature showed very high concordance with the MammaPrintH results Conclusions and Significance We demonstrate that data generated from FFPE material with the DASL assay if properly processed are comparable to data extracted from the FF counterpart Specifically gene expression profiles for a known set of prognostic genes for a specific disease are highly comparable between two conditions This opens up the possibility of using both FFPE and FFmaterial in gene expressions analyses leading to a vast increase in the potential resources available for cancer research See article Categories Abstract Poster 18 Accreditation 1 BluePrint

    Original URL path: http://www.agendia.com/gene-expression-profiles-from-formalin-fixed-paraffin-embedded-breast-cancer-tissue-are-largely-comparable-to-fresh-frozen-matched-tissue/ (2016-05-01)
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  • TSPYL5 suppresses p53 levels and function by physical interaction with USP7 | Agendia
    a gene expression signature that is a powerful predictor of poor clinical outcome in breast cancer 1 Among the seventy genes in this expression profile is a gene of unknown function TSPYL5 TSPY like 5 also known as KIAA1750 TSPYL5 is located within a small region at chromosome 8q22 that is frequently amplified in breast cancer which suggests that TSPYL5 has a causal role in breast oncogenesis 2 3 Here we report that high TSPYL5 expression is an independent marker of poor outcome in breast cancer Mass spectrometric analysis revealed that TSPYL5 interacts with ubiquitin specific protease 7 USP7 also known as herpesvirus associated ubiquitin specific protease HAUSP USP7 is the deubiquitylase for the p53 tumour suppressor 4 and TSPYL5 reduces the activity of USP7 towards p53 resulting in increased p53 ubiquitylation We demonstrate that TSPYL5 reduces p53 protein levels and inhibits activation of p53 target genes Furthermore expression of TSPYL5 overrides p53 dependent proliferation arrest and oncogene induced senescence and contributes to oncogenic transformation in multiple cell based assays Our data identify TSPYL5 as a suppressor of p53 function through its interaction with USP7 See article Categories Abstract Poster 18 Accreditation 1 BluePrint 9 Clinical Studies 8 ColoPrint 5

    Original URL path: http://www.agendia.com/tspyl5-suppresses-p53-levels-and-function-by-physical-interaction-with-usp7/ (2016-05-01)
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  • Cost-Effectiveness of 70-Gene MammaPrint Signature in Node-Negative Breast Cancer | Agendia
    payer perspective Methods A Markov model with 3 health states was constructed In the base case model risk classiἀcation and patient outcomes were based on a 70 gene signature validation study Efficacy of chemotherapy was derived from a published meta analysis of clinical trials An alternative model using data from AS and from the Surveil lance Epidemiology and End Results registry was built to examine the external validity of the base case model The incremental beneἀts costs and cost effectiveness of treatment guided by 70 gene signature were calculated Results In the base case model 70 gene signature reclassified 29 of patients and spared 10 of patients from chemotherapy Compared with the AS strategy the 70 gene signature strategy was associated with 1440 higher total cost per patient and with 0 14 additional life year or 0 15 additional quality adjusted life year Overall the incremental cost effectiveness ratios were ap proximately 10 000 per life year or quality ad justed life year in the base case model and 700 in the alternative model The model results were sensitive to estrogen receptor status the propor tion of patients classiἀed as high risk vs low risk and the overall survival in

    Original URL path: http://www.agendia.com/cost-effectiveness-of-70-gene-mammaprint-signature-in-node-negative-breast-cancer/ (2016-05-01)
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  • Biological Functions of the Genes in the Mammaprint Breast Cancer Profile Reflect the Hallmarks of Cancer | Agendia
    using the expression of 70 genes To better understand the tumor biology assessed by MammaPrint we interpreted the biological functions of the 70 genes and showed how the genes reflect the six hallmarks of cancer as defined by Hanahan and Weinberg Results We used a bottom up system biology approach to elucidate how the cellular processes reflected by the 70 genes work together to regulate tumor activities and progression The biological functions of the genes were analyzed using literature research and several bioinformatics tools Protein protein interaction network analyses indicated that the 70 genes form highly interconnected networks and that their expression levels are regulated by key tumorigenesis related genes such as TP53 RB1 MYC JUN and CDKN2A The biological functions of the genes could be associated with the essential steps necessary for tumor progression and metastasis and cover the six well defined hallmarks of cancer reflecting the acquired malignant characteristics of a cancer cell along with tumor progression and metastasis related biological activities Conclusion Genes in the MammaPrint gene signature comprehensively measure the six hallmarks of cancer related biology This finding establishes a link between a molecular signature and the underlying molecular mechanisms of tumor cell progression and metastasis

    Original URL path: http://www.agendia.com/biological-functions-of-the-genes-in-the-mammaprint-breast-cancer-profile-reflect-the-hallmarks-of-cancer/ (2016-05-01)
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