Abstract 63P
Background
HER2 status is a crucial prognostic and predictive biomarker in invasive breast cancer (BC). The advent of novel-anti HER2 therapies (e.g. Trastuzumab Deruxtecan (T-DXd)) has cast doubt upon traditional HER2 detection methods, as emerging data indicates the effectiveness of T-DXd in individuals categorized as HER2 immunohistochemistry (IHC) 1+ or 0 scores. More sensitive methods detecting HER2-low expression are key to identify patients who could benefit from treatment with novel anti-HER2 therapeutics. As IHC methods were developed for identifying HER2 overexpression, rather than distinguishing between HER2-low and expression absence, the ability of IHC to detect HER2-low cases remains uncertain. APIS Breast Cancer Subtyping Kit (APIS BCSK) was developed to detect expression level of four BC biomarkers – HER2, ER, PR, Ki67. Here, we report HER2 mRNA expression levels detected by APIS BCSK, in correlation with IHC HER2 scoring.
Methods
Formalin-fixed paraffin-embedded (FFPE) BC sections (n=642), from core needle biopsy or resection, underwent histological assessment observing the ASCO/CAP guidelines for IHC. HER2 status of specimens with a HER2 2+ IHC score was resolved via in situ hybridization (ISH) amplification. All specimens were tested with APIS BCSK. To evaluate diagnostic accuracy of the kit, IHC/ISH and APIS BCSK mRNA expression level concordance was reported as Overall Percent Agreement (OPA), Negative Percent Agreement (NPA), and Positive Percent Agreement (PPA).
Results
Strong correlation between IHC/ISH results and HER2 expression detected by APIC BCSK was observed (OPA of 94.2%, PPA of 89.2% and NPA of 94.9%). ERBB2 mRNA expression was detected by APIS BCSK in a subset of patients with 0 and 1+ IHC HER2 score, highlighting the continuous nature of ERBB2 expression and higher sensitivity of RT-qPCR-based detection approaches.
Conclusions
APIS BCSK accurately detects HER2 expression. Results confirm that IHC stratification may not be an adequate method for predicting the response to novel anti-HER2 therapies, such as T-DXd. Implementation of additional cut offs could allow further stratification of ERBB2 mRNA expression, however, additional studies are required to validate this approach.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.