Abstract P4-02-03: Impact of the 2018 ASCO/CAP HER2 focused update on human epidermal growth factor receptor-2 (HER2) testing in breast cancer: A retrospective review of a single institutional cohort
Authors: Hicks DG , D'Aguiar M , Henry J , McMahon L , Buscaglia B , Turner B 
Published: May 2019

Abstract
Background: In the 2013 ASCO/CAP HER2 update, new recommendations for HER2 diagnostic criteria in breast cancer organized in situ hybridization (ISH) results into five categories; group1 (amplified), group 2 (monosomy), group 3 (co-amplified), group 4 (equivocal) and group 5 (non-amplified). Patients falling into groups 2, 3 and 4 were potentially eligible for HER2 targeted therapy, however, there is uncertainty from limited prospective clinical trials that show patients in these uncommon groups would receive the same benefit as group 1. Concern over whether the interpretation criteria should be modified for these uncommon groups led to the recent publication of the 2018 HER2 focused update. This update has modified ISH criteria for groups 2, 3 and 4, recommending the final diagnosis take into consideration both immunohistochemistry (IHC) and ISH results. The publication of this new guideline has prompted us to investigate what impact this would have on our institution.
Materials & Methods: A retrospective review of the URMC pathology database revealed 2,281 cases that had undergone HER2 FISH analysis since the 2013 update. IHC for initial HER2 screening was used, followed by reflex testing of all 2+ results and cases with histopathologic discordance. All 2,281 FISH cases were sorted into their 5 HER2 categories based on the 2013 guidelines. The final HER2 diagnosis for groups 2, 3 and 4 were then re-determined after applying the new criteria presented in the 2018 focused update.
Results: The results from the 2,281 HER2 FISH cases are shown in Tables 1 and 2. The results for group 1 and group 5 cases remained the same. However, for ISH cases in groups 2, 3 and 4, there were alterations in the final HER2 results. All 25 monosomy cases, originally interpreted as HER2 positive by the 2013 guidelines, were now considered HER2 negative. All group 3 (co-amplified) cases remained positive (due to IHC 2+ results). The largest change was that the original 199 equivocal cases, based on the 2013 guidelines, became split into 198 HER2 negative (99.5%) and 1 HER2 positive (0.5%).
Conclusion: Comparison of the HER2 FISH cases between 2013 and 2018 revealed differences in the final HER2 status. Using the 2018 guideline, 13.72% (313 cases) of the 2281 cases were HER2 positive in contrast to 14.77% (337 cases) from 2013. While that is only a difference of 1.05%, the reclassification of 198 of 199 equivocal cases to negative indicates that 9.82% of the final HER2 results for the entire patient cohort was affected. With 266,000 new cases of breast cancer annually, the final HER2 status of approximately 26,000 patients and their potential eligibility for targeted-therapy would change. Further study of the clinical significance of these changes is warranted.
Final ISH HER2 Status (2013)AmplifiedMonosomyCo-AmplifiedEquivocalNon-Amplified272 cases (11.93%)25 cases (1.10%)40 cases (1.75%)199 cases (8.72%)1,745 cases (76.50%)
Citation Format: Hicks DG, D'Aguiar M, Henry J, McMahon L, Buscaglia B, Turner B. Impact of the 2018 ASCO/CAP HER2 focused update on human epidermal growth factor receptor-2 (HER2) testing in breast cancer: A retrospective review of a single institutional cohort [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-02-03.