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Agreement between molecular subtyping and surrogate subtype classification: a contemporary population-based study of ER-positive/HER2-negative primary breast cancer
PURPOSE: Oestrogen receptor-positive (ER+) and human epidermal receptor 2-negative (HER2–) breast cancers are classified as Luminal A or B based on gene expression, but immunohistochemical markers are used for surrogate subtyping. The aims of this study were to examine the agreement between molecula...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer US
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6797629/ https://www.ncbi.nlm.nih.gov/pubmed/31432367 http://dx.doi.org/10.1007/s10549-019-05378-7 |
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author | Lundgren, Christine Bendahl, Pär-Ola Borg, Åke Ehinger, Anna Hegardt, Cecilia Larsson, Christer Loman, Niklas Malmberg, Martin Olofsson, Helena Saal, Lao H. Sjöblom, Tobias Lindman, Henrik Klintman, Marie Häkkinen, Jari Vallon-Christersson, Johan Fernö, Mårten Rydén, Lisa Ekholm, Maria |
author_facet | Lundgren, Christine Bendahl, Pär-Ola Borg, Åke Ehinger, Anna Hegardt, Cecilia Larsson, Christer Loman, Niklas Malmberg, Martin Olofsson, Helena Saal, Lao H. Sjöblom, Tobias Lindman, Henrik Klintman, Marie Häkkinen, Jari Vallon-Christersson, Johan Fernö, Mårten Rydén, Lisa Ekholm, Maria |
author_sort | Lundgren, Christine |
collection | PubMed |
description | PURPOSE: Oestrogen receptor-positive (ER+) and human epidermal receptor 2-negative (HER2–) breast cancers are classified as Luminal A or B based on gene expression, but immunohistochemical markers are used for surrogate subtyping. The aims of this study were to examine the agreement between molecular subtyping (MS) and surrogate subtyping and to identify subgroups consisting mainly of Luminal A or B tumours. METHODS: The cohort consisted of 2063 patients diagnosed between 2013–2017, with primary ER+/HER2– breast cancer, analysed by RNA sequencing. Surrogate subtyping was performed according to three algorithms (St. Gallen 2013, Maisonneuve and our proposed Grade-based classification). Agreement (%) and kappa statistics (κ) were used as concordance measures and ROC analysis for luminal distinction. Ki67, progesterone receptor (PR) and histological grade (HG) were further investigated as surrogate markers. RESULTS: The agreement rates between the MS and St. Gallen 2013, Maisonneuve and Grade-based classifications were 62% (κ = 0.30), 66% (κ = 0.35) and 70% (κ = 0.41), respectively. PR did not contribute to distinguishing Luminal A from B tumours (auROC = 0.56). By classifying HG1-2 tumours as Luminal A-like and HG3 as Luminal B-like, agreement with MS was 80% (κ = 0.46). Moreover, by combining HG and Ki67 status, a large subgroup of patients (51% of the cohort) having > 90% Luminal A tumours could be identified. CONCLUSIONS: Agreement between MS and surrogate classifications was generally poor. However, a post hoc analysis showed that a combination of HG and Ki67 could identify patients very likely to have Luminal A tumours according to MS. |
format | Online Article Text |
id | pubmed-6797629 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Springer US |
record_format | MEDLINE/PubMed |
spelling | pubmed-67976292019-11-01 Agreement between molecular subtyping and surrogate subtype classification: a contemporary population-based study of ER-positive/HER2-negative primary breast cancer Lundgren, Christine Bendahl, Pär-Ola Borg, Åke Ehinger, Anna Hegardt, Cecilia Larsson, Christer Loman, Niklas Malmberg, Martin Olofsson, Helena Saal, Lao H. Sjöblom, Tobias Lindman, Henrik Klintman, Marie Häkkinen, Jari Vallon-Christersson, Johan Fernö, Mårten Rydén, Lisa Ekholm, Maria Breast Cancer Res Treat Epidemiology PURPOSE: Oestrogen receptor-positive (ER+) and human epidermal receptor 2-negative (HER2–) breast cancers are classified as Luminal A or B based on gene expression, but immunohistochemical markers are used for surrogate subtyping. The aims of this study were to examine the agreement between molecular subtyping (MS) and surrogate subtyping and to identify subgroups consisting mainly of Luminal A or B tumours. METHODS: The cohort consisted of 2063 patients diagnosed between 2013–2017, with primary ER+/HER2– breast cancer, analysed by RNA sequencing. Surrogate subtyping was performed according to three algorithms (St. Gallen 2013, Maisonneuve and our proposed Grade-based classification). Agreement (%) and kappa statistics (κ) were used as concordance measures and ROC analysis for luminal distinction. Ki67, progesterone receptor (PR) and histological grade (HG) were further investigated as surrogate markers. RESULTS: The agreement rates between the MS and St. Gallen 2013, Maisonneuve and Grade-based classifications were 62% (κ = 0.30), 66% (κ = 0.35) and 70% (κ = 0.41), respectively. PR did not contribute to distinguishing Luminal A from B tumours (auROC = 0.56). By classifying HG1-2 tumours as Luminal A-like and HG3 as Luminal B-like, agreement with MS was 80% (κ = 0.46). Moreover, by combining HG and Ki67 status, a large subgroup of patients (51% of the cohort) having > 90% Luminal A tumours could be identified. CONCLUSIONS: Agreement between MS and surrogate classifications was generally poor. However, a post hoc analysis showed that a combination of HG and Ki67 could identify patients very likely to have Luminal A tumours according to MS. Springer US 2019-08-20 2019 /pmc/articles/PMC6797629/ /pubmed/31432367 http://dx.doi.org/10.1007/s10549-019-05378-7 Text en © The Author(s) 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. |
spellingShingle | Epidemiology Lundgren, Christine Bendahl, Pär-Ola Borg, Åke Ehinger, Anna Hegardt, Cecilia Larsson, Christer Loman, Niklas Malmberg, Martin Olofsson, Helena Saal, Lao H. Sjöblom, Tobias Lindman, Henrik Klintman, Marie Häkkinen, Jari Vallon-Christersson, Johan Fernö, Mårten Rydén, Lisa Ekholm, Maria Agreement between molecular subtyping and surrogate subtype classification: a contemporary population-based study of ER-positive/HER2-negative primary breast cancer |
title | Agreement between molecular subtyping and surrogate subtype classification: a contemporary population-based study of ER-positive/HER2-negative primary breast cancer |
title_full | Agreement between molecular subtyping and surrogate subtype classification: a contemporary population-based study of ER-positive/HER2-negative primary breast cancer |
title_fullStr | Agreement between molecular subtyping and surrogate subtype classification: a contemporary population-based study of ER-positive/HER2-negative primary breast cancer |
title_full_unstemmed | Agreement between molecular subtyping and surrogate subtype classification: a contemporary population-based study of ER-positive/HER2-negative primary breast cancer |
title_short | Agreement between molecular subtyping and surrogate subtype classification: a contemporary population-based study of ER-positive/HER2-negative primary breast cancer |
title_sort | agreement between molecular subtyping and surrogate subtype classification: a contemporary population-based study of er-positive/her2-negative primary breast cancer |
topic | Epidemiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6797629/ https://www.ncbi.nlm.nih.gov/pubmed/31432367 http://dx.doi.org/10.1007/s10549-019-05378-7 |
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