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HER2 and TOP2A amplification in a hospital-based cohort of breast cancer patients: associations with patient and tumor characteristics

  • Epidemiology
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Abstract

Gene amplification is an important factor for altered gene expression in breast cancers. TOP2A-amplification often occurs concomitantly with HER2 amplification, and it has been suggested to be predictive for the response to anthracycline chemotherapy. This study assessed the correlation between HER2 status and TOP2A co-amplification, the possible association of TOP2A single-nucleotide polymorphisms with the frequency of this co-amplification as well as confirmation of association with outcome. HER2 and TOP2A amplification were analyzed in a tissue microarray from a clinical cohort study. Additionally, a common genetic variant (rs13695) in the TOP2A gene was genotyped in germline DNA. HER2 gene amplification was compared with HER2-IHC findings assessed during clinical routine work, and the association between all the biomarkers analyzed and the clinical outcome was determined. As an exploratory aim, rs13695 genotypes were compared with TOP2A amplification status. HER2 amplification was seen in 101 of 628 (16.1 %) and TOP2A amplification in 32 (5.1 %) cancers. No TOP2A amplification occurred without HER2 co-amplification. HER2 amplification was found in 8, 13.6, and 55.1 % of patients with HER2-IHC 0/1+, 2+, and 3+ tumors, respectively. HER2-IHC was not associated with an effect on the prognosis, but HER2-FISH was. There was an association between the rs13695 genotype and TOP2A amplification status (P = 0.03). Although there was a significant correlation between HER2 status determined by IHC and HER2 by FISH, only HER2 gene amplification status by FISH was correlated with outcome indicating greater utility for FISH in routine clinical settings.

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Acknowledgments

Research for the present study was supported by a grant from the Bavaria California Technology Center (www.bacatec.de) and grants from the California Breast Cancer Research Program (BCRP 12IB-0155 to MFPress) and Breast Cancer Research Foundation (MFPress). Peter A. Fasching was funded by a grant from the Dr. Mildred Scheel Foundation of German Cancer Aid (Deutsche Krebshilfe e.V.).

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The authors declare they have no conflict of interest.

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Authors and Affiliations

  1. Division of Hematology/Oncology, Department of Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA

    Peter A. Fasching & Dennis J. Slamon

  2. Department of Gynecology and Obstetrics, Erlangen University Hospital, University Breast Center for Franconia, Friedrich-Alexander University of Erlangen–Nuremberg, Erlangen, Germany

    Peter A. Fasching, Sebastian Weihbrecht, Lothar Haeberle & Matthias W. Beckmann

  3. Department of Pathology, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA

    Armen Gasparyan, Ivonne E. Villalobos, Yanling Ma & Michael F. Press

  4. Institute of Human Genetics, Friedrich-Alexander University of Erlangen–Nuremberg, Erlangen, Germany

    Arif B. Ekici

  5. Erlangen University Hospital, Institute of Pathology, Friedrich-Alexander University of Erlangen–Nuremberg, Erlangen, Germany

    David L. Wachter & Arndt Hartmann

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  1. Peter A. Fasching
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Correspondence to Peter A. Fasching.

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Fasching, P.A., Weihbrecht, S., Haeberle, L. et al. HER2 and TOP2A amplification in a hospital-based cohort of breast cancer patients: associations with patient and tumor characteristics. Breast Cancer Res Treat 145, 193–203 (2014). https://doi.org/10.1007/s10549-014-2922-x

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