Agreement between molecular subtyping and surrogate subtype classification : a contemporary population-based study of ER-positive/HER2-negative primary breast cancer
| Autor: | Jari Häkkinen, Anna Ehinger, Tobias Sjöblom, Christine Lundgren, Marie Klintman, Cecilia Hegardt, Martin Malmberg, Lao H. Saal, Mårten Fernö, Helena Olofsson, Åke Borg, Niklas Loman, Pär-Ola Bendahl, Maria Ekholm, Christer Larsson, Johan Vallon-Christersson, Lisa Rydén, Henrik Lindman |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Oncology Cancer Research medicine.medical_specialty Receptor ErbB-2 Epidemiology Breast Neoplasms 03 medical and health sciences 0302 clinical medicine Breast cancer Internal medicine medicine Biomarkers Tumor Humans skin and connective tissue diseases Neoplasm Staging Intrinsic subtype Cancer och onkologi business.industry Surrogate endpoint HER2 negative medicine.disease Subtyping Tumor Burden Population based study Gene Expression Regulation Neoplastic 030104 developmental biology Molecular Diagnostic Techniques Receptors Estrogen 030220 oncology & carcinogenesis Population Surveillance Cancer and Oncology Immunohistochemistry Female Gene expression Neoplasm Grading Surrogate marker Subtype classification business Primary breast cancer Molecular subtyping |
| Zdroj: | Breast Cancer Research and Treatment |
| Popis: | 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 (kappa) 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% (kappa = 0.30), 66% (kappa = 0.35) and 70% (kappa = 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% (kappa = 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. |
| Databáze: | OpenAIRE |
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