Abstract PO3-15-07: False-negative results of hyperexpression of HER2 receptor in breast cancer at a public tertiary hospital in Brazil
Authors: Batista Bruno , Ioshii Sergio , Padilha Sergio , Nabhen Jacqueline , Ostroski Tayza , Batista Caroline 
Published: May 2024

Introduction: Breast cancer (BC) is the second leading cause of cancer death in women worldwide. One of the major advances in BC management was its molecular classification, especially regarding the Human Epidermal growth factor Receptor 2 (HER2). HER2 positive tumors are at greater risk of visceral metastasis and are associated with worse survival rates. Thus, the use of specific drugs to target this pathway is essential and false-negative have a high impact on patient care. HER2 status is usually accessed using immunohistochemistry (IHC), but false-negatives results occur. When IHC results are inconclusive, in-situ hybridization (ISH) testing is necessary. Objective: to determine if there is variability between the positivity rates between laboratories that performed the ISH, according to the IHQ, and to evaluate if there are false-negative results and possible prognostic impact. Methods: retrospective, observational study in a public hospital in the city of Curitiba (Brazil), followed by cross-sectional analysis of histological samples. All cases of BC that underwent HER2 assessment by IHC and ISH between January 2008 and December 2018 were included. Participants classified as HER2 negative by IHC and patients whose medical records were not available were excluded. A new analysis of all IHC slides and of cases with negative ISH was performed. Results: We identified 205 people with an average age of 53.52 (± 11.89) years. Most cases were classified as clinical stage I and II (68.3%), and the most prevalent histological features were Invasive Ductal Carcinoma (82.4%) and luminal molecular subtype (49.8%). Initial ISH testing was performed by four laboratories. There was a significant difference in HER2 positivity rates between these laboratories, even after individual reanalysis of all IHC slides. Of the 114 cases with negative ISH, it was possible to obtain histological material in 82 of them to perform a new standardized ISH. The false-negative rate for HER2 in this 82 patients was 41.46%, with 10 cases out of 24 for positive IHC (3+) and 22 out of 58 for inconclusive IHC (2+). In this paper, false-negative results did not impact in survival, most likely to differences between groups. Conclusion: our work showed different rates of positivity for HER2 among laboratories that performed confirmatory test with ISH. The performance of a second standardized ISH proved that the difference between the laboratories was due to false-negative results. There was no difference in recurrence and cancer-specific survival in this false-negative sample.

Keywords: breast cancer. Biomarkers. Health technology assessment. HER2 receptor.

DIfferences between laboratories reagarding HER2 false negatives

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Citation Format: Bruno Batista, Sergio Ioshii, Sergio Padilha, Jacqueline Nabhen, Tayza Ostroski, Caroline Batista. False-negative results of hyperexpression of HER2 receptor in breast cancer at a public tertiary hospital in Brazil [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-15-07.