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  • Daily clinical practice of fresh tumour tissue freezing and gene expression profiling; logistics pilot study preceding the MINDACT trial. | Agendia
    D Sabadell G MacGrogan L J van t Veer F Cardoso E J Rutgers February 14 2009 Purpose The 70 gene prognosis signature is a prognostic tool for early breast cancer analysis In addition to scientific evidence implementation of the signature in clinical trials and daily practice requires logistical feasibility The aim of our study was to test logistics for gene expression profiling on fresh frozen tumour tissue in the preparation for the prospective multinational Microarray In Node negative Disease may Avoid ChemoTherapy MINDACT trial Methods Sixty four patients were included in six European hospitals Fresh frozen tumour samples were shipped on dry ice to Agendia B V where RNAwas isolated and subsequently hybridised on the 70 gene prognosis signature MammaPrintTM Results Tumour samples were obtained in 60 of 64 patients Among the 60 samples 11 contained insufficient tumour cells 50 and three contained insufficient RNA quality All 46 samples eligible for genomic profiling were successfully hybridised and the results were reported on average within 4 5d Conclusion Gene expression profiling on fresh frozen tissue is feasible in daily clinical practice See article Categories Abstract Poster 18 Accreditation 1 BluePrint 9 Clinical Studies 8 ColoPrint 5 Cost Effectiveness 6 Development

    Original URL path: http://www.agendia.com/daily-clinical-practice-of-fresh-tumour-tissue-freezing-and-gene-expression-profiling-logistics-pilot-study-preceding-the-mindact-trial/ (2016-05-01)
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  • The 70-gene signature as a response predictor for neoadjuvant chemotherapy in breast cancer. | Agendia
    Jeanne T F D Vrancken Peeters Harm van Tinteren Laura J van t Veer Sjoerd Rodenhuis February 13 2009 The 70 gene signature MammaPrintTM is a prognostic tool used to guide adjuvant treatment decisions The aim of this study was to assess its value to predict chemosensitivity in the neoadjuvant setting We obtained the 70 gene profile of stage II III patients prior to neoadjuvant chemotherapy and classified the prognosis signatures Pathological complete remission pCR was used to measure chemosensitivity Among 167 patients 144 86 were having a poor and 23 14 a good prognosis signature None of the good prognosis signature patients achieved a pCR 0 23 whereas 29 144 patients 20 in the poor prognosis signature group did P 0 015 All triple negative tumors n 38 had a poor prognosis signature Within the non triple negative sub group the response of the primary tumor remained associated with the classification of the prognosis signature P 0 023 A pCR is unlikely to be achieved in tumors that have a good prognosis signature Tumors with a poor prognosis signature are more sensitive to chemotherapy See article Categories Abstract Poster 18 Accreditation 1 BluePrint 9 Clinical Studies 8 ColoPrint 5

    Original URL path: http://www.agendia.com/the-70-gene-signature-as-a-response-predictor-for-neoadjuvant-chemotherapy-in-breast-cancer/ (2016-05-01)
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  • Prediction of adjuvant chemotherapy benefit in endocrine responsive, early breast cancer using multigene assays. | Agendia
    review summarizes these data and provides a perspective on the limitations and clinical utility of these assays Methods The literature regarding multigene assays and signatures in early breast cancer was surveyed Only two assays the 21 gene recurrence score RS assay Oncotype DX and the 70 gene signature MammaPrint were analyzed in randomized or non randomized clinical populations in order to determine the predictive utility of the test in the adjuvant chemotherapy setting in patients whose tumors were estrogen receptor positive These data are summarized by type of clinical analysis with information on clinical utility and comparative studies with standard clinical pathologic factors Results From 2 independent analyses in phase III clinical trial settings with tamoxifen alone control arms the 21 gene RS assay defines a group of patients with low scores who do not appear to benefit from chemotherapy and a second group with very high scores who derive major benefit from CMF or CAF chemotherapy One study was conducted in node negative disease and the second in a node positive population Interaction terms were significant in both studies and the effect of the assay remained upon adjustment for other standard factors Utilizing a non randomized clinical setting the 70 gene signature could also predict chemotherapy benefit in the high risk group versus no apparent benefit in the low risk group an effect that remained after adjustment for standard factors For both assays the discordance rate between the assay prediction and clinical pathologic risk category was approximately 30 Clinical utility studies showed use of the assay results in a change in treatment decision in 25 30 of cases most commonly from chemoendocrine therapy to endocrine therapy alone Summary The prediction of adjuvant chemotherapy benefit over and above endocrine therapy using multigene assay determined risk category differs greatly across risk

    Original URL path: http://www.agendia.com/prediction-of-adjuvant-chemotherapy-benefit-in-endocrine-responsive-early-breast-cancer-using-multigene-assays/ (2016-05-01)
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  • Clinical Application of the 70-Gene Profile: The MINDACT Trial | Agendia
    the potential to greatly improve risk assessment and treatment decision making for early breast cancer Its prospective validation is currently ongoing through the MINDACT Microarray in Node Negative Disease May Avoid Chemotherapy trial a 6 000 patient randomized multicentric trial This article reviews the several steps in the development of the profile from its discovery to its clinical validation See article Categories Abstract Poster 18 Accreditation 1 BluePrint 9 Clinical

    Original URL path: http://www.agendia.com/clinical-application-of-the-70-gene-profile-the-mindact-trial/ (2016-05-01)
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  • Use of a 70-Gene Signature to predict prognosis of patients with node-negative breast cancer: a prospective community-based feasibility study (RASTER). | Agendia
    Healthcare Improvement CBO and other guidelines Methods Between January 2004 and December 2006 812 women aged under 61 years with primary breast carcinoma clinical T1 4N0M0 were enrolled Fresh tumour samples were collected in 16 hospitals in the Netherlands within 1 h after surgery Clinico pathological factors were collected and microarray analysis was done with a custom designed array chip that assessed the mRNA expression index of the 70 genes previously identified for the prognostic signature Patients with a good signature were deemed to have a good prognosis and therefore could be spared adjuvant systemic treatment with its associated adverse effects whereas patients with a poor signature were judged to have a poor prognosis and should be considered for adjuvant systemic treatment Concordance between risk predicted by the prognosis signature and risk predicted by commonly used clinicopathological guidelines i e St Gallen guidelines Nottingham Prognostic Index and Adjuvant Online was assessed Findings of 585 eligible patients 158 patients were excluded because of sampling failure n 128 and incorrect procedure n 30 Prognosis signatures were assessed in 427 patients The 70 gene prognosis signature identified 219 51 patients with good prognosis and 208 49 patients with poor prognosis The Dutch CBO guidelines identified 184 patients 43 with poor prognosis which was discordant with those findings obtained with the prognosis signature in 128 30 patients Oncologists recommended adjuvant treatment in 203 48 patients based on Dutch CBO guidelines in 265 62 patients if the guidelines were used with the prognosis signature and in 259 61 patients if Dutch CBO guidelines prognosis signature and patients preferences for treatment were all taken into account Adjuvant Online guidelines identified more patients with poor prognosis than did the signature alone 294 69 and discordance with the signature occurred in 160 37 patients St Gallen guidelines identified

    Original URL path: http://www.agendia.com/use-of-a-70-gene-signature-to-predict-prognosis-of-patients-with-node-negative-breast-cancer-a-prospective-community-based-feasibility-study-raster/ (2016-05-01)
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  • Robust interlaboratory reproducibility of a gene expression signature measurement consistent with the needs of a new generation of diagnostic tools | Agendia
    J Van t Veer June 7 2007 Background The increasing use of DNA microarrays in biomedical research toxicogenomics pharmaceutical development and diagnostics has focused attention on the reproducibility and reliability of microarray measurements While the reproducibility of microarray gene expression measurements has been the subject of several recent reports there is still a need for systematic investigation into what factors most contribute to variability of measured expression levels observed among different laboratories and different experimenters Results We report the results of an interlaboratory comparison of gene expression array measurements on the same microarray platform in which the RNA amplification and labeling hybridization and wash and slide scanning were each individually varied Identical input RNA was used for all experiments While some sources of variation have measurable influence on individual microarray signals they showed very low influence on sample to reference ratios based on averaged triplicate measurements in the two color experiments RNA labeling was the largest contributor to interlaboratory variation Conclusion Despite this variation measurement of one particular breast cancer gene expression signature in three different laboratories was found to be highly robust showing a high intralaboratory and interlaboratory reproducibility when using strictly controlled standard operating procedures See article Categories

    Original URL path: http://www.agendia.com/robust-interlaboratory-reproducibility-of-a-gene-expression-signature-measurement-consistent-with-the-needs-of-a-new-generation-of-diagnostic-tools/ (2016-05-01)
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  • Converting a breast cancer microarray signature into a high-throughput diagnostic test. | Agendia
    disease outcome in young breast cancer patients This profile however was generated on microarrays containing 25 000 60 mer oligonucleotides that are not designed for processing of many samples on a routine basis Results To facilitate its use in a diagnostic setting the 70 gene prognosis profile was translated into a customized microarray MammaPrint containing a reduced set of 1 900 probes suitable for high throughput processing RNA of 162 patient samples from two previous studies was subjected to hybridization to this custom array to validate the prognostic value Classification results obtained from the original analysis were then compared to those generated using the algorithms based on the custom microarray and showed an extremely high correlation of prognosis prediction between the original data and those generated using the custom mini array p 0 0001 Conclusion In this report we demonstrate for the first time that microarray technology can be used as a reliable diagnostic tool The data clearly demonstrate the reproducibility and robustness of the small custom made microarray The array is therefore an excellent tool to predict outcome of disease in breast cancer patients See article Categories Abstract Poster 18 Accreditation 1 BluePrint 9 Clinical Studies 8 ColoPrint 5

    Original URL path: http://www.agendia.com/converting-a-breast-cancer-microarray-signature-into-a-high-throughput-diagnostic-test/ (2016-05-01)
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  • Mammary gland biology and breast cancer. Conference on Common Molecular Mechanisms of Mammary Gland Development and Breast Cancer Progression | Agendia
    the multitude of possibilities that the mammary gland offers to experimental biologists The mammary gland has many unique developmental features it goes through embryonal puberty pregnancy lactation and post lactation phases and many of the genetic determinants that regulate cell specification proliferation differentiation survival and death have been studied in great detail Growth differentiation and regression of the mammary epithelial cells occur repeatedly in the adult organism Each cycle of pregnancy lactation and involution is accompanied by massive cellular proliferation functional differentiation and cell death These developmental stages are regulated by epithelial stromal cell interactions and by systemically and locally acting steroid and peptide hormones Hennighausen Robinson 2005 Genetic analyses can be carried out using tissue specific knockout mice or genetically mofified primary cells can be transplanted into fat pads cleared of endogenous epithelium These experimental strategies have been recently complemented by the isolation and genetic manipulation of adult mammary stem cells The basic scientific aspects of mammary gland biology are not only fascinating but also central to our understanding of breast cancer which is at present the most common cancer in women in the Western world Extensive research is underway to being carried out the basic biology of the

    Original URL path: http://www.agendia.com/mammary-gland-biology-and-breast-cancer-conference-on-common-molecular-mechanisms-of-mammary-gland-development-and-breast-cancer-progression/ (2016-05-01)
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