TEST:

PATHWAY antiHer2/neu (4B5) Rabbit Monoclonal Primary Antibody

Of two patients with the HER2-ultralow phenotype, one was alive with no evidence of disease at 16 months follow-up. The results support the idea that HER2/neu overexpression is exceptionally rare in LGSOC; nevertheless, future trials are essential to fully characterize the spectrum of HER2/neu alterations in LGSOC and to determine definitively whether the rare cases with mutations or ultralow expression could represent a small subgroup that might benefit from specific targeted agents.

P1, N=45, Recruiting, Baylor College of Medicine | Trial primary completion date: Dec 2025 --> Dec 2026

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.

P1, N=17, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting | N=37 --> 17

AI-assisted interpretation improved observer agreement (Kappa: 0.703 vs. 0.610 in non-amplified cases) and reduced ambiguous immunohistochemistry (IHC) 2+/0 assignments. These findings delineate distinct clinicopathological characteristics of HER2-ultralow/null tumors, highlight HER2 IHC reproducibility challenges, and validate AI as an effective tool for standardizing scoring to optimize patient selection for T-DXd therapy.

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.

Flexibility of the complementarity-determining region loops in 4B5 imparts paratope plasticity that enables interaction with AKR1B family proteins. This antibody off-target recognition can result in cytoplasmic and nuclear IHC staining.

Patients with metastatic HER2-low breast cancer (BC), defined as IHC 1+ or IHC 2+/ISH-negative, have demonstrated clinical benefit from antibody-drug conjugates (ADCs) such as trastuzumab deruxtecan...As HER2-targeted therapies expand to HER2-UL tumors, accurate classification is critical. Implementation of a refined scoring system could improve diagnostic accuracy and therapeutic targeting.

Clinical labeling of the data was provided by reference laboratory pathologists with expertise in advanced oncological morphology evaluations. This dataset allows training and validation of machine learning models for the diagnosis, recognition, and classification of breast cancer using the available labeling, as well as for educational purposes for residents and pathologists.

Our data showed a notable variation in HER2-low BC frequency across Dutch pathology laboratories, even among those using the same antibody and detection system. These differences may influence patient eligibility for T-DXd.

It also illustrates that the case can obtain different HER2 IHC scores with different assays being used. Therefore, it is suggested for pathologists to recognize the pitfalls in HER2 IHC, be aware of the assay that is being used in their laboratory and hence evaluate the results in the accurate context.