TEST:

HercepTest

P=N/A, N=350, Not yet recruiting, AstraZeneca | Trial completion date: Jan 2026 --> Nov 2026 | Initiation date: Aug 2025 --> Apr 2026 | Trial primary completion date: Jan 2026 --> Nov 2026

P1/2, N=270, Completed, Dragonfly Therapeutics | Recruiting --> Completed | Trial completion date: Dec 2026 --> Dec 2025 | Trial primary completion date: Oct 2026 --> Dec 2025

HER2 staining was lower in 4B5 testing than in the HercepTest. Companion diagnosis using 4B5 is required to determine indications for T-DXd, especially for HER2-ultralow evaluations.

DG44 identified a significantly higher proportion of HER2-(ultra)low cases and showed the most variability in HER2 status between matched primary tumors and metastases compared to 4B5 and SP3. The choice of HER2 assay can lead to discrepancies in HER2 status assessment, which could directly influence patient eligibility for T-DXd treatment.

The developed methodologies can be used to stratify HER2 low-expression patient groups, potentially improving the interpretation of IHC assays and maximizing therapeutic benefits. This method can be implemented in histology labs without requiring a specialized workflow.

This is the first evaluation of HER2/ERBB2 expression in GBC with PBM based on WES, HercepTest, and FISH. The significant increase in ERBB2 expression, driven by the synergistic interplay between GBC and PBM, underscores a critical molecular interaction that may inform the development of targeted therapeutic strategies.

Pure ACs on the PATHWAY 4B5 platform primarily present HER2 cytoplasmic granular staining in TNAC and HER2 low expression cases. The rate of HER2 cytoplasmic granular staining on HercepTest platform was significantly lower than that of PATHWAY 4B5, and is more suitable for the detection and interpretation of HER2 0 and low expression cases.

P=N/A, N=350, Not yet recruiting, AstraZeneca

The discordance of HER2 staining depended on the sample size and antibody clone. Tissue stained with 4B5 (CNB or EB), but not with CNB-HercepTest, correlated with mRNA values.

P1, N=10, Completed, Tomsk National Research Medical Center of the Russian Academy of Sciences | Recruiting --> Completed

P=N/A, N=10, Completed, Tomsk National Research Medical Center of the Russian Academy of Sciences | Enrolling by invitation --> Completed

The advent of highly effective HER2-targeted antibody-drug conjugates with clinical activity at low levels of HER2 expression, such as trastuzumab deruxtecan, has necessitated the re-evaluation of HER2 testing, particularly for HER2-low tumours...We discuss the importance of accurately defining HER2-low expression for therapeutic decision-making and how newer diagnostic approaches, such as quantitative immunofluorescence and RNA-based assays, might address the limitations of traditional immunohistochemistry-based methods. As the use of HER2-targeted therapies continues to expand to a wider range of tumour types, ensuring the precision and accuracy of HER2 testing will be crucial for guiding treatment strategies and improving patient outcomes.