Cross comparison and prognostic assessment of breast cancer multigene signatures in a large population-based contemporary clinical series
Autor: | Cecilia Hegardt, Lao H. Saal, Henrik Lindman, Anna Ehinger, Niklas Loman, Lisa Rydén, Jari Häkkinen, Johan Staaf, Johan Vallon-Christersson, Tobias Sjöblom, Åke Borg, Martin Malmberg, Helena Olofsson, Fredrik Wärnberg, Christer Larsson |
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Jazyk: | angličtina |
Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
Oncology Risk medicine.medical_specialty Prognostic variable Antineoplastic Agents Hormonal Receptor ErbB-2 Population lcsh:Medicine Triple Negative Breast Neoplasms Disease Kaplan-Meier Estimate Article 03 medical and health sciences 0302 clinical medicine Breast cancer Internal medicine Databases Genetic medicine Humans education lcsh:Science Transcriptomics skin and connective tissue diseases education.field_of_study Cancer och onkologi Multidisciplinary medicine.diagnostic_test business.industry lcsh:R Gene signature medicine.disease Prognosis Gene Expression Regulation Neoplastic 030104 developmental biology Receptors Estrogen Chemotherapy Adjuvant Cancer and Oncology Cohort Immunohistochemistry lcsh:Q Female business Oncotype DX Transcriptome 030217 neurology & neurosurgery Follow-Up Studies |
Zdroj: | Scientific Reports Scientific Reports, Vol 9, Iss 1, Pp 1-16 (2019) |
Popis: | Multigene expression signatures provide a molecular subdivision of early breast cancer associated with patient outcome. A gap remains in the validation of such signatures in clinical treatment groups of patients within population-based cohorts of unselected primary breast cancer representing contemporary disease stages and current treatments. A cohort of 3520 resectable breast cancers with RNA sequencing data included in the population-based SCAN-B initiative (ClinicalTrials.gov ID NCT02306096) were selected from a healthcare background population of 8587 patients diagnosed within the years 2010–2015. RNA profiles were classified according to 19 reported gene signatures including both gene expression subtypes (e.g. PAM50, IC10, CIT) and risk predictors (e.g. Oncotype DX, 70-gene, ROR). Classifications were analyzed in nine adjuvant clinical assessment groups: TNBC-ACT (adjuvant chemotherapy, n = 239), TNBC-untreated (n = 82), HER2+/ER− with anti-HER2+ ACT treatment (n = 110), HER2+/ER+ with anti-HER2 + ACT + endocrine treatment (n = 239), ER+/HER2−/LN− with endocrine treatment (n = 1113), ER+/HER2−/LN− with endocrine + ACT treatment (n = 243), ER+/HER2−/LN+ with endocrine treatment (n = 423), ER+/HER2−/LN+ with endocrine + ACT treatment (n = 433), and ER+/HER2−/LN− untreated (n = 200). Gene signature classification (e.g., proportion low-, high-risk) was generally well aligned with stratification based on current immunohistochemistry-based clinical practice. Most signatures did not provide any further risk stratification in TNBC and HER2+/ER– disease. Risk classifier agreement (low-, medium/intermediate-, high-risk groups) in ER+ assessment groups was on average 50–60% with occasional pair-wise comparisons having |
Databáze: | OpenAIRE |
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