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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
Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Dept Oncol, Region Jönköping County, Sweden; Lund Univ, Sweden.
Lund Univ, Sweden.
Lund Univ, Sweden.
Lund Univ, Sweden.
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2019 (English)In: Breast Cancer Research and Treatment, ISSN 0167-6806, E-ISSN 1573-7217, Vol. 178, no 2, p. 459-467Article in journal (Refereed) Published
Abstract [en]

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 amp;gt; 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.

Place, publisher, year, edition, pages
SPRINGER , 2019. Vol. 178, no 2, p. 459-467
Keywords [en]
Breast cancer; Intrinsic subtype; Molecular subtyping; Surrogate marker; Gene expression
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:liu:diva-161594DOI: 10.1007/s10549-019-05378-7ISI: 000491200400022PubMedID: 31432367OAI: oai:DiVA.org:liu-161594DiVA, id: diva2:1368211
Note

Funding Agencies|Swedish Breast Cancer Association; Swedish Breast Cancer Group; Futurum-the Academy for Health and Care, Region Jonkoping County

Available from: 2019-11-06 Created: 2019-11-06 Last updated: 2019-11-06

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Lundgren, ChristineEkholm, Maria
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