Comparison of molecular subtyping by conventional local pathology assessment or by microarray analysis using an 80-gene signature in ER+ early stage breast cancer patients

Steenhoven, J.E.C. van (2017) Comparison of molecular subtyping by conventional local pathology assessment or by microarray analysis using an 80-gene signature in ER+ early stage breast cancer patients. thesis, Medicine.

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Abstract

Background and aim Gene expression profiling has become an accepted method to determine risk of developing metastases, but can also be deployed to determine intrinsic molecular breast cancer subtypes. The aim of the present study was to compare the classification of molecular tumor subtypes based on conventional pathology assessment to a classification based on an 80 gene-signature (80-GS). Patients and methods In a prospective multicenter study into the effect of 70 gene-signature (70-GS) use on chemotherapy decision making in clinical intermediate risk ER+ breast cancers, surrogate molecular subtypes (Luminal/HER2/Basal) were determined for all patients (n=595) by local pathology assessment using immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). For a subset of patients (n=48) Ki67 assessment was available and used to further stratify Luminal-type tumors into Luminal A and B. At Agendia Laboratories an 80-GS was performed to categorize cancers as Luminal, HER2 or Basal-type and by adding the 70-GS a sub stratification of Luminal type tumors into A and B could be performed. Comparison of molecular subtypes (Luminal/HER2/Basal) classified by IHC/FISH and an 80- GS was done for all patients. Comparison of Luminal A and Luminal B tumors could be performed in the subset of patients in whom Ki-67 was assessed. Results Between January 1st 2013 and December 31st 2015, 595 patients, treated in 23 hospitals, were enrolled. Using local pathology as surrogate molecular subtyping; 98% of patients (n=578) were regarded as Luminal-type and 2% (n=12) as HER2-type. Comparison of surrogate molecular subtyping versus an 80-GS resulted in an overall concordance of 97%. In the subset of patients (n=48) in whom Ki67 was assessed 25% (n=12) and 75% (n=36) of patients were classified as Luminal A and Luminal B, respectively. Within this subgroup, 25% of patients (n=3) regarded as Luminal A by local pathology were reclassified as Luminal B by the 80-GS. Fifty-eight percent (n=21) of patients regarded as Luminal B by local pathology were reclassified as Luminal A by gene-expression subtyping (Kappa 0.11 [95%CI -0.14 – 0.34 ]). Conclusion In this group of predominantly ER+/HER2- Dutch breast cancer patients we observed high concordance between intrinsic molecular subtyping using conventional pathology assessment or gene-expression profiling. Although the number of patients who were considered to have HER2-type tumors was limited most of them were reclassified as Luminal-type tumors by gene-expression profiling. In the selection of patients in whom Ki67 expression was assessed, the sub stratification of Luminal-type tumors into A and B revealed high discordance between local pathology and gene-expression profiling.

Item Type:	Thesis (Thesis)
Supervisor name:	Supervisor (1th): and Dalen, Thijs van surgeon and Supervisor (2th): and surgeon, Robert Pierik and Department and institution: Department of Surgery, Diakoness and University of Groningen
Faculty:	Medical Sciences
Date Deposited:	25 Jun 2020 10:54
Last Modified:	25 Jun 2020 10:54
URI:	https://umcg.studenttheses.ub.rug.nl/id/eprint/1534

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