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  • MammaPrint Molecular Diagnostics on Formalin-Fixed, Paraffin-Embedded Tissue. | Agendia
    has been available for fresh tissue Improvements in RNA processing have enabled microarray diagnostics for formalin fixed paraffin embedded FFPE tissue Here we describe method optimization validation and performance of MammaPrint using analyte from FFPE tissue Laboratory procedures for enabling the assay to be run on FFPE tissue were determined using 157 samples and the assay was established using 125 matched FFPE and fresh tissues Validation of MammaPrint FFPE compared with MammaPrint fresh was performed on an independent series of matched tissue from five hospitals nZ211 Reproducibility repeatability and precision of the FFPE assay nZ87 was established for duplicate analysis of the same tumor inter laboratory performance 20 day repeat experiments and repeated analyses over 12 months FFPE sample processing had a success rate of 97 The MammaPrint assay using FFPE analyte demonstrated an overall equivalence of 91 5 95 confidence interval 86 9 to 94 5 between the 211 independent matched FFPE and fresh tumor samples Precision was 97 3 and repeatability was 97 8 with highly reproducible results between replicate samples of the same tumor and between two laboratories concordance 96 Thus with 580 tumor samples MammaPrint was successfully translated to FFPE tissue The assay has high precision

    Original URL path: http://www.agendia.com/mammaprint-molecular-diagnostics-on-formalin-fixed-paraffin-embedded-tissue/ (2016-05-01)
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  • Performance Characteristics of the MammaPrint Breast Cancer Diagnostic Gene Signature | Agendia
    Publication Name Personalized Medicine Author s Leonie JM Delahaye Diederik Wehkamp Arno N Floore Rene Bernards Laura J van t Veer1 Annuska M Glas November 1 2013 The analytical performance of multigene signatures depends on many parameters including precision repeatability reproducibility and intratumor heterogeneity Indicators such as sensitivity specificity positive predictive value and negative predictive value are typically used to define the clinical performance of a diagnostic test Aim Here we study these performance characteristics of the MammaPrint Agendia NV Amsterdam The Netherlands 70 gene signature using the US FDA recommended guidelines as well as predetermined acceptance criteria Results The clinical and analytical performance characteristics show that MammaPrint is a robust reproducible precise test with a maximum variation of 5 in multiple samplings of the same tissue Conclusion MammaPrint is a reliable indicator of distant metastasis in early stage breast cancer patients of all ages and is well suited for personalized medical care See article Categories Abstract Poster 18 Accreditation 1 BluePrint 9 Clinical Studies 8 ColoPrint 5 Cost Effectiveness 6 Development 8 Impact Study 2 MammaPrint 40 MINDACT 5 News 56 Predictive 3 Press Release 53 Publications 58 Review Article 10 St Gallen Guidelines 2 TargetPrint 4 Treatment Impacts

    Original URL path: http://www.agendia.com/performance-characteristics-of-the-mammaprint-breast-cancer-diagnostic-gene-signature/ (2016-05-01)
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  • Estrogen receptor splice variants as a potential source of false-positive estrogen receptor status in breast cancer diagnostics | Agendia
    658 ERa positive HER2 negative breast tumors for ERa and progesterone receptor PR status as determined by mRNA expression and for their molecular subtypes Luminal type vs Basal type assessed by BluePrint molecular subtyping assay In addition we assessed the recurrence risk low vs high using the 70 gene MammaPrint signature We found that 55 out of 2 658 2 1 tumors that are ERa positive by mRNA analysis also demonstrate a Basal molecular subtype indicating that they lack expression of estrogenresponsive genes These ERa positive Basal type tumors express significantly lower levels of both ERa and PR mRNA as compared to Luminal type tumors P 0001 and almost invariably 94 5 have a high risk MammaPrint profile Twelve of the MammaPrint genes are directly ERa responsive indicating that MammaPrint assesses ERa function in breast cancer without considering ERa mRNA levels We find a relatively high expression of the dominant negative ERa splice variant ERD7 in ERapositive Basal type tumors as compared to ERa positive Luminal type tumors P 0001 Expression of the dominant negative ERa variant ERD7 provides a rationale as to why tumors are of the Basal molecular subtype while staining ERa positive by immunohistochemistry These tumors may

    Original URL path: http://www.agendia.com/estrogen-receptor-splice-variants-as-a-potential-source-of-false-positive-estrogen-receptor-status-in-breast-cancer-diagnostics/ (2016-05-01)
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  • Molecular subtyping of early-stage breast cancer identifies a group of patients who do not benefit from neoadjuvant chemotherapy | Agendia
    was to analyze the correlation between the pathologic complete response pCR rate after neoadjuvant chemotherapy and long term outcome distant metastases free survival DMFS in patients with early stage breast cancer using BluePrint and MammaPrint molecular subtyping versus clinical subtyping using immunohistochemistry fluorescence in situ hybridization IHC FISH for the determination of estrogen receptor progesterone receptor and human epidermal growth factor receptor 2 HER2 Data were analyzed from 437 patients in four neoadjuvant chemotherapy trials BluePrint and MammaPrint outcomes were determined from 44K Agilent arrays the I SPY 1 data portal or Affymetrix U133A arrays The pCR rate differed substantially among BluePrint molecular subgroups 6 in Luminal A type 10 in Luminal B type 47 in HER2 type and 37 in Basal type patients In the Luminal A type group n 90 including seven HER2 positive patients and eight triple negative patients by IHC FISH the 5 year DMFS rate was 93 The pCR rate provided no prognostic information suggesting these patients may not benefit from chemotherapy Forty three of 107 40 HER2 positive patients were classified as Luminal type by BluePrint and may have lower response rates to targeted therapy Molecular subtyping identified 90 of 435 21 patients as Luminal A type BluePrint Luminal type MammaPrint Low Risk with excellent survival The pCR rate provided no prognostic information Molecular subtyping can improve the stratification of patients in the neoadjuvant setting Luminal A type MammaPrint Low Risk patients have a good prognosis with excellent survival and do not seem to benefit from chemotherapy We observed marked benefit in response and DMFS to neoadjuvant treatment in patients subtyped as HER2 type and Basal type BluePrint with MammaPrint molecular subtyping helps to improve prognostic estimation and the choice of therapy versus IHC FISH See Article Categories Abstract Poster 18 Accreditation 1 BluePrint

    Original URL path: http://www.agendia.com/response-and-long-term-outcomes-after-neo-adjuvant-chemotherapy-pooled-dataset-of-patients-stratified-by-molecular-subtyping-using-mammaprint-and-blueprint/ (2016-05-01)
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  • Independent Validation of a Prognostic Genomic Signature (ColoPrint) for Patients With Stage II Colon Cancer | Agendia
    PhD January 9 2013 Objectives The aim of this study was to independently validate a genomic signature developed both to assess recurrence risk in stage II patients and to assist in treatment decisions Background Adjuvant therapy is recommended for high risk patients with stage II colon cancer but better tools to assess the patients prognosis accurately are still required Methods Previously an 18 gene signature had been developed and validated on an independent cohort using full genome microarrays In this study the gene signature was translated and validated as a robust diagnostic test ColoPrint using customized 8 pack arrays In addition clinical validation of the diagnostic ColoPrint assay was performed on 135 patients who underwent curative resection R0 for colon cancer stage II in Munich Fresh frozen tissue microsatellite instability status clinical parameters and follow up data for all patients were available The diagnostic ColoPrint readout was determined blindly from the clinical data Results ColoPrint identified most stage II patients 73 3 as at low risk The 5 year distant metastasis free survival was 94 9 for low risk patients and 80 6 for high risk patients In multivariable analysis ColoPrint was the only significant parameter to predict the development of distant metastasis with a hazard ratio of 4 28 95 confidence interval 1 36 13 50 P 0 013 Clinical risk parameters from the American Society of Clinical Oncology ASCO recommendation did not add power to the ColoPrint classification Technical validation of ColoPrint confirmed stability and reproducibility of the diagnostic platform Conclusions ColoPrint is able to predict the development of distant metastasis of patients with stage II colon cancer and facilitates the identification of patients who may be safely managed without chemotherapy See article Categories Abstract Poster 18 Accreditation 1 BluePrint 9 Clinical Studies 8 ColoPrint 5 Cost Effectiveness

    Original URL path: http://www.agendia.com/independent-validation-of-a-prognostic-genomic-signature-coloprint-for-patients-with-stage-ii-colon-cancer/ (2016-05-01)
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  • Cost Effectiveness of Gene Expression Profiling for Early Stage Breast Cancer | Agendia
    women with lymph nodenegative estrogen receptor positive early stage breast cancer who are most likely to benefit from adjuvant chemotherapy The authors of this report evaluated the cost effectiveness of recurrence score guided treatment using 2 commercially available GEP tests Oncotype DX Genomic Health Redwood City Calif and MammaPrint Agendia Inc Irvine Calif from a third party payer s perspective METHODS A 10 year Markov model was developed to compare the costs and quality adjusted life years QALYs of treatment decisions guided by either Oncotype DX or MammaPrint in a hypothetical cohort of women with early stage lymph nodenegative estrogen receptor positive breast cancer who may experience recurrence Outcomes included no recurrence recurrence and death The costs considered included gene test costs the costs of adjuvant chemotherapy and other chemotherapy including premedication oncology visits and monitoring for adverse events the cost of treating recurrence costs associated with the treatment of adverse events and end of life care costs RESULTS The model demonstrated that the patients who received the Oncotype DX test to guide treatment spent 27 882 in US dollars and gained 7 364 QALYs whereas patients who received the MammaPrint test to guide treatment spent 21 598 and gained 7 461 QALYs Sensitivity analyses demonstrated that the results were robust to changes in all parameters CONCLUSIONS The model suggested that MammaPrint is a more cost effective GEP test compared with Oncotype DX at a threshold willingness to pay of 50 000 per QALY Because Oncotype DX is the most frequently used GEP in clinical practice in the United States the authors concluded that the current findings have implications for health policy particularly health insurance reimbursement decisions Cancer 2012 000 000 000 VC 2012 American Cancer Society See article Categories Abstract Poster 18 Accreditation 1 BluePrint 9 Clinical Studies 8

    Original URL path: http://www.agendia.com/cost-effectiveness-of-gene-expression-profiling-for-early-stage-breast-cancer/ (2016-05-01)
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  • Comparison of Molecular Subtyping with BluePrint, MammaPrint, and TargetPrint to Local Clinical Subtyping in Breast Cancer Patients | Agendia
    Edgardo Rivera Katharine Yao Femke A de Snoo Jeroen van den Akker Lisette Stork Sloots Daniele Generali August 15 2012 Purpose To compare breast cancer subtyping with the three centrally assessed microarray based assays BluePrint MammaPrint and TargetPrint with locally assessed clinical subtyping using immunohistochemistry IHC and fluorescence in situ hybridization FISH Methods BluePrint MammaPrint and TargetPrint were all performed on fresh tumor samples Microarray analysis was performed at Agendia Laboratories blinded for clinical and pathological data IHC FISH assessments were performed according to local practice at each institution estrogen receptor ER progesterone receptor PR and human epidermal growth factor receptor 2 HER2 assessments were performed on 132 samples and Ki 67 on 79 samples Results The concordance between BluePrint and IHC FISH subtyping was 94 for the Luminal type 95 for the HER2 type and 94 for the Basal type subgroups The concordance of BluePrint with subtyping using mRNA single gene readout TargetPrint was 96 for the Luminal type 97 for the HER2 type and 98 for the Basal type subgroups The concordance for substratification into Luminal A and B using MammaPrint and Ki 67 was 68 The concordance between TargetPrint and IHC FISH was 97 for ER 80 for PR and 95 for HER2 Conclusions The implementation of multigene assays such as TargetPrint BluePrint and MammaPrint may improve the clinical management of breast cancer patients High discordance between Luminal A and B substratification based on MammaPrint versus locally assessed Ki 67 or grade indicates that chemotherapy decisions should not be based on the basis of Ki 67 readout or tumor grade alone TargetPrint serves as a second opinion for those local pathology settings where high quality standardization is harder to maintain See article Categories Abstract Poster 18 Accreditation 1 BluePrint 9 Clinical Studies 8 ColoPrint 5 Cost Effectiveness

    Original URL path: http://www.agendia.com/comparison-of-molecular-subtyping-with-blueprint-mammaprint-and-targetprint-to-local-clinical-subtyping-in-breast-cancer-patients/ (2016-05-01)
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  • The EORTC 10041/BIG 03-04 MINDACT trial is feasible: Results of the pilot phase | Agendia
    Disease may Avoid ChemoTherapy trial investigates the clinical utility of the 70 gene profile MammaPrint for the selection of breast cancer patients for adjuvant chemotherapy CT together with standard clinicopathological criteria We present the results of the pilot phase consisting of first 800 patients included Methods MINDACT has enrolled 6600 patients classified into high or low risk by Mamma Print and clinicopathological risk through Adjuvant Online Patients with both clinical C and genomic G high risks are offered adjuvant CT those with both C and G low risks do not receive CT patients with discordant risk are randomised for the decision of adjuvant CT based on C or G risk CT randomisation of anthracycline based versus docetaxel capecitabine and endocrine therapy randomisation between letrozole and tamoxifen letrozole are offered Results During the pilot phase 46 of screened patients were enrolled Main reasons for non enrolment were node positivity before trial amendment sample quality problems and failure to meet logistic settings Among the 800 patients 386 48 were C low Glow 198 24 8 as C high G high 75 9 4 as C low G high and 141 17 6 as C high G See article Categories Abstract Poster 18

    Original URL path: http://www.agendia.com/the-eortc-10041big-03-04-mindact-trial-is-feasible-results-of-the-pilot-phase/ (2016-05-01)
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