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Concordance of Immunohistochemistry-Based and Gene Expression-Based Subtyping in Breast Cancer

BACKGROUND: Use of immunohistochemistry-based surrogates of molecular breast cancer subtypes is common in research and clinical practice, but information on their comparative validity and prognostic capacity is scarce. METHODS: Data from 2 PAM50-subtyped Swedish breast cancer cohorts were used: Stoc...

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Autores principales: Holm, Johanna, Yu, Nancy Yiu-Lin, Johansson, Annelie, Ploner, Alexander, Hall, Per, Lindström, Linda Sofie, Czene, Kamila
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791620/
https://www.ncbi.nlm.nih.gov/pubmed/33442660
http://dx.doi.org/10.1093/jncics/pkaa087
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author Holm, Johanna
Yu, Nancy Yiu-Lin
Johansson, Annelie
Ploner, Alexander
Hall, Per
Lindström, Linda Sofie
Czene, Kamila
author_facet Holm, Johanna
Yu, Nancy Yiu-Lin
Johansson, Annelie
Ploner, Alexander
Hall, Per
Lindström, Linda Sofie
Czene, Kamila
author_sort Holm, Johanna
collection PubMed
description BACKGROUND: Use of immunohistochemistry-based surrogates of molecular breast cancer subtypes is common in research and clinical practice, but information on their comparative validity and prognostic capacity is scarce. METHODS: Data from 2 PAM50-subtyped Swedish breast cancer cohorts were used: Stockholm tamoxifen trial–3 with 561 patients diagnosed 1976-1990 and Clinseq with 237 patients diagnosed 2005-2012. We evaluated 3 surrogate classifications; the immunohistochemistry-3 surrogate classifier based on estrogen receptor, progesterone receptor, and HER2 and the St. Gallen and Prolif surrogate classifiers also including Ki-67. Accuracy, kappa, sensitivity, and specificity were computed as compared with PAM50. Alluvial diagrams of misclassification patterns were plotted. Distant recurrence-free survival was assessed using Kaplan-Meier plots, and tamoxifen treatment benefit for luminal subtypes was modeled using flexible parametric survival models. RESULTS: The concordance with PAM50 ranged from poor to moderate (kappa = 0.36-0.57, accuracy = 0.54-0.75), with best performance for the Prolif surrogate classification in both cohorts. Good concordance was only achieved when luminal subgroups were collapsed (kappa = 0.71-0.69, accuracy = 0.90-0.91). The St. Gallen surrogate classification misclassified luminal A into luminal B; the reverse pattern was seen with the others. In distant recurrence-free survival, surrogates were more similar to each other than PAM50. The difference in tamoxifen treatment benefit between luminal A and B for PAM50 was not replicated with any surrogate classifier. CONCLUSIONS: All surrogate classifiers had limited ability to distinguish between PAM50 luminal A and B, but patterns of misclassifications differed. PAM50 subtyping appeared to yield larger separation of survival between luminal subtypes than any of the surrogate classifications.
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spelling pubmed-77916202021-01-12 Concordance of Immunohistochemistry-Based and Gene Expression-Based Subtyping in Breast Cancer Holm, Johanna Yu, Nancy Yiu-Lin Johansson, Annelie Ploner, Alexander Hall, Per Lindström, Linda Sofie Czene, Kamila JNCI Cancer Spectr Article BACKGROUND: Use of immunohistochemistry-based surrogates of molecular breast cancer subtypes is common in research and clinical practice, but information on their comparative validity and prognostic capacity is scarce. METHODS: Data from 2 PAM50-subtyped Swedish breast cancer cohorts were used: Stockholm tamoxifen trial–3 with 561 patients diagnosed 1976-1990 and Clinseq with 237 patients diagnosed 2005-2012. We evaluated 3 surrogate classifications; the immunohistochemistry-3 surrogate classifier based on estrogen receptor, progesterone receptor, and HER2 and the St. Gallen and Prolif surrogate classifiers also including Ki-67. Accuracy, kappa, sensitivity, and specificity were computed as compared with PAM50. Alluvial diagrams of misclassification patterns were plotted. Distant recurrence-free survival was assessed using Kaplan-Meier plots, and tamoxifen treatment benefit for luminal subtypes was modeled using flexible parametric survival models. RESULTS: The concordance with PAM50 ranged from poor to moderate (kappa = 0.36-0.57, accuracy = 0.54-0.75), with best performance for the Prolif surrogate classification in both cohorts. Good concordance was only achieved when luminal subgroups were collapsed (kappa = 0.71-0.69, accuracy = 0.90-0.91). The St. Gallen surrogate classification misclassified luminal A into luminal B; the reverse pattern was seen with the others. In distant recurrence-free survival, surrogates were more similar to each other than PAM50. The difference in tamoxifen treatment benefit between luminal A and B for PAM50 was not replicated with any surrogate classifier. CONCLUSIONS: All surrogate classifiers had limited ability to distinguish between PAM50 luminal A and B, but patterns of misclassifications differed. PAM50 subtyping appeared to yield larger separation of survival between luminal subtypes than any of the surrogate classifications. Oxford University Press 2020-10-07 /pmc/articles/PMC7791620/ /pubmed/33442660 http://dx.doi.org/10.1093/jncics/pkaa087 Text en © The Author(s) 2020. Published by Oxford University Press. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Article
Holm, Johanna
Yu, Nancy Yiu-Lin
Johansson, Annelie
Ploner, Alexander
Hall, Per
Lindström, Linda Sofie
Czene, Kamila
Concordance of Immunohistochemistry-Based and Gene Expression-Based Subtyping in Breast Cancer
title Concordance of Immunohistochemistry-Based and Gene Expression-Based Subtyping in Breast Cancer
title_full Concordance of Immunohistochemistry-Based and Gene Expression-Based Subtyping in Breast Cancer
title_fullStr Concordance of Immunohistochemistry-Based and Gene Expression-Based Subtyping in Breast Cancer
title_full_unstemmed Concordance of Immunohistochemistry-Based and Gene Expression-Based Subtyping in Breast Cancer
title_short Concordance of Immunohistochemistry-Based and Gene Expression-Based Subtyping in Breast Cancer
title_sort concordance of immunohistochemistry-based and gene expression-based subtyping in breast cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791620/
https://www.ncbi.nlm.nih.gov/pubmed/33442660
http://dx.doi.org/10.1093/jncics/pkaa087
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