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Mod Pathol. 2018 Apr;31(4):607-615. doi: 10.1038/modpathol.2017.171. Epub 2017 Dec 22.

Clinical relevance and concordance of HER2 status in local and central testing-an analysis of 1581 HER2-positive breast carcinomas over 12 years.

Author information

1
Institute of Pathology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
2
German Breast Group, Neu-Isenburg, Germany.
3
German Cancer Consortium (DKTK), Berlin, Germany.
4
German Cancer Research Center (DKFZ), Heidelberg, Germany.
5
University Women's Hospital Frankfurt, Frankfurt/ Main, Germany.
6
Center of Pathology, Cytology and Molecular Pathology Neuss, Neuss, Germany.
7
European Breast Center, Luisen Hospital, Düsseldorf, Germany.
8
Center of Pathology and Cytology Düsseldorf, Düsseldorf, Germany.
9
Oncology Bethanien, Frankfurt/Main, Germany.
10
Institute of Pathology, University Hospital Frankfurt, Frankfurt/ Main, Germany.
11
Practice of Hematology and Oncology, München, Germany.
12
Practice of Pathology, München, Germany.
13
Division Gynecologic Oncology, National Center for Tumor Diseases, University Hospital Heidelberg, Heidelberg, Germany.
14
Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.
15
Institute of Pathology Essen, University Hospital Essen, Essen, Germany.
16
Institute of Pathology Spandau, Berlin, Germany.
17
Sividon Diagnostics GmbH, Köln, Germany.
18
Gynecological Hospital Sana Klinikum Offenbach, Offenbach, Germany.

Abstract

Human epidermal growth factor receptor 2 (HER2) is a central predictive biomarker in breast cancer. Inaccurate HER2 results in different laboratories could be as high as 20%. However, this statement is based on data generated more than 13 years ago and may not reflect the standards of modern diagnostic pathology. We compared central and local HER2 testing in a total of 1581 HER2-positive tumors from five clinical trials. We evaluated the clinical relevance for pathological complete response (pCR) and disease-free survival in a subgroup of 677 tumors, which received an anti-HER2 therapy. Over the period of 12 years, the discordance rate for HER2 decreased from 52.4 (GeparTrio) to 8.4% (GeparSepto). Discordance rates were significantly higher in hormone receptor (HR)-positive tumors (26.6%), compared to HR-negative tumors (16.3%, P<0.0001), which could be explained by a different distribution of HER2 mRNA levels in HR-positive and HR-negative tumors. pCR rates were significantly lower in discordant tumors (13.7%) compared to concordant tumors (32.2%, GeparQuattro and GeparQuinto, P<0.001). In survival analysis, tumors with discordant HER2 testing had a reduced overall survival (OS) in the HR-negative group (P=0.019) and a trend for improved OS in the HR-positive group (P=0.125). The performance of local HER2 testing was considerably improved over time and has reached a 92% concordance, which shows that quality initiatives in diagnostic pathology are working. Tumors with discordant HER2 testing had a reduced therapy response and different survival rates.

PMID:
29271415
DOI:
10.1038/modpathol.2017.171
[Indexed for MEDLINE]
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