Concordance of Immunohistochemistry-Based and Gene Expression-Based Subtyping in Breast Cancer.
Aged
Algorithms
Antineoplastic Agents, Hormonal
/ therapeutic use
Biomarkers, Tumor
/ analysis
Breast Neoplasms
/ chemistry
Cohort Studies
Female
Gene Expression
Genetic Markers
Humans
Immunohistochemistry
Kaplan-Meier Estimate
Ki-67 Antigen
/ analysis
Middle Aged
Prognosis
Protein Array Analysis
ROC Curve
Receptor, ErbB-2
/ analysis
Receptors, Estrogen
/ analysis
Receptors, Progesterone
/ analysis
Sensitivity and Specificity
Sequence Analysis, RNA
Sweden
Tamoxifen
/ therapeutic use
Journal
JNCI cancer spectrum
ISSN: 2515-5091
Titre abrégé: JNCI Cancer Spectr
Pays: England
ID NLM: 101721827
Informations de publication
Date de publication:
02 2021
02 2021
Historique:
received:
30
07
2020
revised:
05
09
2020
accepted:
08
09
2020
entrez:
14
1
2021
pubmed:
15
1
2021
medline:
15
1
2021
Statut:
epublish
Résumé
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. 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. 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. 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.
Sections du résumé
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.
Identifiants
pubmed: 33442660
doi: 10.1093/jncics/pkaa087
pii: pkaa087
pmc: PMC7791620
doi:
Substances chimiques
Antineoplastic Agents, Hormonal
0
Biomarkers, Tumor
0
Genetic Markers
0
Ki-67 Antigen
0
Receptors, Estrogen
0
Receptors, Progesterone
0
Tamoxifen
094ZI81Y45
Receptor, ErbB-2
EC 2.7.10.1
Types de publication
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Informations de copyright
© The Author(s) 2020. Published by Oxford University Press.
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