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Cross comparison and prognostic assessment of breast cancer multigene signatures in a large population-based contemporary clinical series
Lund Univ, Dept Clin Sci Lund, Div Oncol & Pathol, SE-22381 Lund, Sweden.ORCID iD: 0000-0002-2195-0385
Lund Univ, Dept Clin Sci Lund, Div Oncol & Pathol, SE-22381 Lund, Sweden.ORCID iD: 0000-0002-8466-9179
Lund Univ, Dept Clin Sci Lund, Div Oncol & Pathol, SE-22381 Lund, Sweden.
Lund Univ, Dept Clin Sci Lund, Div Oncol & Pathol, SE-22381 Lund, Sweden.
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2019 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 12184Article in journal (Refereed) Published
Abstract [en]

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 <30% agreement. Disregarding the intermediate-risk groups, the exact agreement between low- and high-risk groups was on average similar to 80-95%, for risk prediction signatures across all assessment groups. Outcome analyses were restricted to assessment groups of TNBC-ACT and endocrine treated ER+/HER2-/LN- and ER+/HER2-/LN+ cases. For ER+/HER2- disease, gene signatures appear to contribute additional prognostic value even at a relatively short follow-up time. Less apparent prognostic value was observed in the other groups for the tested signatures. The current study supports the usage of gene expression signatures in specific clinical treatment group within population-based breast cancer. It also stresses the need of further development to reach higher consensus in individual patient classifications, especially for intermediate-risk patients, and the targeting of patients where current gene signatures and prognostic variables provide little support in clinical decision-making.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP , 2019. Vol. 9, article id 12184
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Cancer and Oncology
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URN: urn:nbn:se:uu:diva-393727DOI: 10.1038/s41598-019-48570-xISI: 000481999500038PubMedID: 31434940OAI: oai:DiVA.org:uu-393727DiVA, id: diva2:1355553
Funder
Swedish Research CouncilSwedish Cancer Society, CAN 2018/685The Crafoord FoundationBioCARE - Biomarkers in Cancer Medicine Improving Health Care Education and InnovationKing Gustaf V Jubilee FundAvailable from: 2019-09-30 Created: 2019-09-30 Last updated: 2019-09-30Bibliographically approved

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Vallon-Christersson, JohanHäkkinen, JariEhinger, AnnaLindman, HenrikOlofsson, HelenaSjöblom, TobiasWärnberg, Fredrik
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