Cross comparison and prognostic assessment of breast cancer multigene signatures in a large population-based contemporary clinical series
(2019) In Scientific Reports 9.- Abstract
- 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... (More)
- 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 ~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 groups 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. (Less)
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https://lup.lub.lu.se/record/ba6c0a32-c4e1-468b-8318-8804d5c083c9
- author
- organization
-
- Breastcancer-genetics
- BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
- Tumor Cell Biology (research group)
- Division of Translational Cancer Research
- Personalized Breast Cancer Treatment (research group)
- The Liquid Biopsy and Tumor Progression in Breast Cancer (research group)
- Breast Cancer Surgery (research group)
- Surgery (Lund)
- Tumor microenvironment
- Familial Breast Cancer (research group)
- publishing date
- 2019-08-21
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Scientific Reports
- volume
- 9
- article number
- 12184
- publisher
- Nature Publishing Group
- external identifiers
-
- scopus:85071073365
- pmid:31434940
- ISSN
- 2045-2322
- DOI
- 10.1038/s41598-019-48570-x
- project
- Sweden Cancerome Analysis Network - Breast (SCAN-B): a large-scale multicenter infrastructure towards implementation of breast cancer genomic analyses in the clinical routine
- Genomisk karakterisering av trippelnegativ bröstcancer (TNBC)
- language
- English
- LU publication?
- yes
- id
- ba6c0a32-c4e1-468b-8318-8804d5c083c9
- date added to LUP
- 2019-08-23 13:08:54
- date last changed
- 2022-05-11 20:43:03
@article{ba6c0a32-c4e1-468b-8318-8804d5c083c9, abstract = {{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 ~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 groups 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.}}, author = {{Vallon-Christersson, Johan and Häkkinen, Jari and Hegardt, Cecilia and Saal, Lao and Larsson, Christer and Ehinger, Anna and Lindman, H and Olofsson, Helena and Sjoblom, Tobias and Wärnberg, Fredrik and Rydén, Lisa and Loman, Niklas and Malmberg, Martin and Borg, Åke and Staaf, Johan}}, issn = {{2045-2322}}, language = {{eng}}, month = {{08}}, publisher = {{Nature Publishing Group}}, series = {{Scientific Reports}}, title = {{Cross comparison and prognostic assessment of breast cancer multigene signatures in a large population-based contemporary clinical series}}, url = {{http://dx.doi.org/10.1038/s41598-019-48570-x}}, doi = {{10.1038/s41598-019-48570-x}}, volume = {{9}}, year = {{2019}}, }