TEST:

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

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.

P=N/A, N=30, Recruiting, Blokhin's Russian Cancer Research Center | Trial completion date: Apr 2025 --> Sep 2027 | Trial primary completion date: Apr 2025 --> Sep 2027

Targeted NGS has the potential in distinguishing HER2 IHC 3+, 2+, and 1+ tumors from IHC 0 in patients with BC; however, differentiating between HER2 IHC 1+ and 0 remains challenging. Additionally, targeted NGS may aid in the identification of actionable mutations, thereby contributing to the selection of optimal treatment strategies in BC management.

Trastuzumab deruxtecan showed improved efficacy compared with treatment of physician's choice in human epidermal growth factor receptor 2 (HER2)-low (immunohistochemistry [IHC] 1+ or IHC 2+/in situ hybridization-negative) metastatic breast cancer (BC) patients in the DESTINY-Breast04 and -06 phase 3 clinical trials...Across assay types, postalignment PPA ranged from 61.6%-95.5% and postalignment NPA ranged from 36.9%-81.7%. The variation in concordance rates observed between assays suggests assay choice may be important for correct identification of patients with low-levels of HER2-expression who may benefit from HER2-targeted therapies.

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