Utility of prognostic genomic tests in breast cancer practice: The IMPAKT 2012 Working Group Consensus Statement

Breast Cancer Translational Research Laboratory (BCTL), J.C. Heuson , Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
Annals of Oncology (Impact Factor: 7.04). 01/2013; 24(3). DOI: 10.1093/annonc/mds645
Source: PubMed


We critically evaluated the available evidence on genomic tests in breast cancer to define their prognostic ability and likelihood to determine treatment benefit.DesignIndependent evaluation of six genomic tests [Oncotype Dx™, MammaPrint(®), Genomic Grade Index, PAM50 (ROR-S), Breast Cancer Index, and EndoPredict] was carried out by a panel of experts in three parameters: analytical validity, clinical validity, and clinical utility based on the principles of the EGAPP criteria.Panel statementsThe majority of the working group members found the available evidence on the analytical and clinical validity of Oncotype Dx™ and MammaPrint(®) to be convincing. None of the genomic tests demonstrated robust evidence of clinical utility: it was not clear from the current evidence that modifying treatment decisions based on the results of a given genomic test could result in improving clinical outcome.Conclusions
The IMPAKT 2012 Working Group proposed the following recommendations: (i) a need to develop models that integrate clinicopathologic factors along with genomic tests; (ii) demonstration of clinical utility should be made in the context of a prospective randomized trial; and (iii) the creation of registries for patients who are subjected to genomic testing in the daily practice.

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    • "The extent of this variation remains unclear. To refine risk estimations and provide a more tailored AST recommendation for the individual patient, gene expression prognosis classifiers have been developed [9]. One of these gene expression classifiers is the 70-gene signature (MammaPrinte, Agendia Inc., Amsterdam, The Netherlands) [10]. "
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    ABSTRACT: Background Clinical decision-making in patients with early stage breast cancer requires adequate risk estimation by medical oncologists. This survey evaluates the agreement among oncologists on risk estimations and adjuvant systemic treatment (AST) decisions and the impact of adding the 70-gene signature to known clinico-pathological factors. Methods Twelve medical oncologists assessed 37 breast cancer cases (cT1–3N0M0) and estimated their risk of recurrence (high or low) and gave a recommendation for AST. Cases were presented in two written questionnaires sent 4 weeks apart. Only the second questionnaire included the 70-gene signature result. Results The level of agreement among oncologists in risk estimation (κ = 0.57) and AST recommendation (κ = 0.57) was ‘moderate’ in the first questionnaire. Adding the 70-gene signature result significantly increased the agreement in risk estimation to ‘substantial’ (κ = 0.61), while agreement in AST recommendations remained ‘moderate’ (κ = 0.56). Overall, the proportion of high risk was reduced with 7.4% (range: 6.9–22.9%; p < 0.001) and the proportion of chemotherapy that was recommended was reduced with 12.2% (range: 5.4–29.5%; p < 0.001). Conclusion Oncologists’ risk estimations and AST recommendations vary greatly. Even though the number of participating oncologists is low, our results underline the need for a better standardisation tool in clinical decision-making, in which integration of the 70-gene signature may be helpful in certain subgroups to provide patients with individualised, but standardised treatment.
    European journal of cancer (Oxford, England: 1990) 04/2014; 50(6). DOI:10.1016/j.ejca.2014.01.016 · 5.42 Impact Factor
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    • "Therefore, the hypothesis was generated that knowledge of the biological background of the tumor may be helpful in the identification of patients with screen-detected tumors at such a low risk of recurrence that they are likely to be overdiagnosed. Nowadays, gene-expression classifiers are used in addition to clinico-pathological factors to identify patients with a favorable prognosis based on the biology of their tumor [8]. One of these gene-expression classifiers is the 70-gene signature (MammaPrint™), developed to improve the selection of those patients who may benefit from adjuvant systemic treatment [9]. "
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    Breast cancer research: BCR 10/2013; 15(5):R92. DOI:10.1186/bcr3493 · 5.49 Impact Factor
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