Abstract P2-03-08: A retrospective study to identify the frequency of discordant HER2 results using both immunohistochemistry (IHC) and in-situ hybridization (ISH) assays
Authors: Balasubramanian A , Ireland-Jenkin K , McDonald A , Khor R , Yeo B , Leong T 
Published: February 2018

Abstract
Background
HER2 targeted therapies have substantially improved survival outcomes for patients with breast cancer and HER2 amplification of their tumour. The recently updated American Society of Clinical Oncology/College of American Pathologists (ASCO CAP) guidelines recommend that HER2 testing to be performed on all invasive breast cancers and that positive HER2 status is defined by either evidence of HER2 protein over-expression measured by immunohistochemistry status (IHC 3+) or by in-situ hybridisation (ISH) amplification. Equivocal results require further testing with the alternative assay.
In Australia, Medicare-funded access to HER2 targeted therapies requires demonstration of HER2 positivity by ISH, regardless of IHC status. Thus, currently most breast units perform IHC and ISH on all breast cancers. Given this discrepancy in practice and significant additional cost of performing ISH, this study evaluated the frequency of discordance and the cost burden in using both assays in a historical series of patients with breast cancer.
Methods
A retrospective audit of HER2 histopathology reports was performed for all breast cancers diagnosed between 2007 and 2016 at a single tertiary hospital in Melbourne, Australia (The Austin Hospital). HER2 IHC results were classified as negative (0 or 1+), equivocal (2+) or positive (3+). An analysis was performed to assess the proportion of concordant (defined as samples with IHC 0/1+ and negative ISH, samples with IHC3+ and positive ISH, and samples with IHC2+ regardless of ISH) and discordant results (defined as IHC 3+ and ISH non-amplified or IHC 0/1+ and ISH amplified). Tumour blocks and slides from discordant cases were reviewed by a breast cancer histopathologist. The cost of additional testing in concordant cases was performed based on the Australian Medicare Benefits Schedule (MBS).
Results
Eight hundred and forty-six histopathology reports were reviewed from 786 patients, all of whom had both IHC and ISH assays. There were 832 (98.8%) concordant cases. There were 10 discordant cases (1.2%) in total, including three cases (0.4%) with a negative IHC (1+) result but positive ISH, and 7 cases (0.8%) with a positive IHC but negative ISH result. A detailed analysis of 10 discordant cases will be presented. HER2 status and subsequent treatment remain unchanged with the addition of ISH testing in 665 (79.0%) cases, which amounted to an additional $209,741 (AUD) being spent on unnecessary ISH testing. Given an estimated incidence of 17,730 new cases of breast cancer per year in Australia, the population cost of performing additional HER2 ISH testing ($315.40 per case) in concordant cases would equate to $4.4 million (AUD) per year.
Conclusion
These results describe an extremely low rate of HER2 IHC/ISH discordance suggesting that routine use of both assays is unnecessary in cases with an unequivocal IHC result. The fiscal burden and potential delays to deciding treatment provide a strong rationale for access to HER2 targeted therapies to be based IHC or ISH, as advised by the ASCO CAP guidelines. Our results will be used to support a national review of IHC and ISH discordance using Australian national registry data.
Citation Format: Balasubramanian A, Ireland-Jenkin K, McDonald A, Khor R, Yeo B, Leong T. A retrospective study to identify the frequency of discordant HER2 results using both immunohistochemistry (IHC) and in-situ hybridization (ISH) assays [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P2-03-08.