Abstract PO3-01-05: Enhancing HER2 Evaluation: Correlation between APIS Breast Cancer Subtyping Kit and IHC/ISH for Accurate HER2 Quantification

Abstract Background: The quantification of HER2-low in breast cancer (BC) has garnered considerable interest due to emerging evidence of the efficacy of targeted therapies in this patient subgroup. Trastuzumab deruxtecan (T-Dxd), an antibody-drug conjugate targeted at HER2, has recently gained approval in the USA and Europe for treating HER2-low BC, which is currently defined as immunohistochemical (IHC) scores of 1+ or 2+ without HER2/ERBB2 in situ hybridization (ISH) amplification. HER2 quantification using IHC/ISH was primarily designed to identify tumors overexpressing HER2, rather than differentiate between HER2-low and the absence of expression. Consequently, the adequacy of these assays in accurately detecting HER2- low remains uncertain. Improving the accuracy of HER2 evaluation is crucial to prevent the incorrect selection of patients for T-Dxd treatment. There is a clear need to develop HER2 testing methods that are more precise, reliable, and capable of detecting HER2-low expression with greater sensitivity and reproducibility. This is particularly important as the minimum threshold of HER2 expression required for T-Dxd efficacy is still under investigation, with clinical data suggesting the potential activity of T-Dxd even in patients with IHC 0 HER2 score. Here, we evaluated the correlation between HER2 mRNA expression levels, detected by APIS Breast Cancer Subtyping Kit, and IHC HER2 classification. Methods: Formalin-fixed paraffin-embedded (FFPE) tumour tissue sections (n=642) obtained by core needle biopsy or resection underwent histological analysis in accordance with laboratory’s standard of care methods. Samples with a HER2 score of 2+ were referred to ISH to determine ERBB2 amplification. To evaluate the diagnostic performance, the concordance between HER2 IHC score, and APIS Breast Cancer Subtyping Kit RNA expression level was reported in terms of Overall Percent Agreement (OPA), Negative Percent Agreement (NPA), and Positive Percent Agreement (PPA), along with their corresponding 95% confidence intervals (CI). Results: HER2 expression detected by APIS Breast Cancer Subtyping Kit showed strong correlation with IHC/ISH, with an OPA of 94.2% (95% CI: 92.2-95.8), PPA of 89.2% (95% CI: 80.1-94.4) and NPA of 94.9% (95% CI: 92.8-96.4). The expression of HER2 was detected by APIS Breast Cancer Subtyping Kit in a subset of patients with 0 and 1+ IHC HER2 scores, suggesting its potential as a more sensitive and reliable method for detection of HER2 expression, and providing the opportunity to enhance HER2 stratification. Conclusions: APIS Breast Cancer Subtyping Kit can accurately detect HER2 expression and has the potential to further stratify the HER2-low patients. Further studies examining the relationship between HER2 expression and the response to anti-HER2 therapies could yield valuable insights into treatment administration and identify patients who could benefit from such therapies. Incorporating continuous quantification of HER2 could optimize patient outcomes. Citation Format: Anna Gasior, Joanna Gorniak, Sara Rollinson, Leanne Gough, Anne-Sophie Wegscheider, Axel Niendorf. Enhancing HER2 Evaluation: Correlation between APIS Breast Cancer Subtyping Kit and IHC/ISH for Accurate HER2 Quantification [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 PO3-01-05.