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When defining HER2-low status in breast cancer, are there certain IHC assays/techniques that are preferred?

Prior studies have shown that there can be significant variation between grading pathologists as to which samples are defined as HER2 IHC +1 versus HER2 IHC 0. How can we address this discrepancy?
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Do the DESTINY-Breast04 results make you more likely to get a second opinion on HER2 IHC testing originally graded as 0?

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4 Answers
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Medical Oncology · Ohio State University Wexner Medical Center
Answered on

As with most IHC evaluations, there are significant variations between grading pathologists. During ASCO 2022, the discussant for DB4, Dr. Patricia LoRusso very eloquently discussed this issue with IHC and specifically, how a more reproducible, quantifiable assay is needed. Until that time, IHC rema...

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Medical Oncology · Cleveland Clinic
Answered on

The VENTANA HER2/neu assay was used for central HER2-testing in the DESTINY-Breast04 trial, along with reflex ISH testing for those with 2+ IHC scores though at the present time, it is reasonable to use any validated HER2 IHC test to assess eligibility for trastuzumab deruxtecan. It is important to ...

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Medical Oncology · University of Iowa Holden Comprehensive Cancer Center
Answered on · Updated on

I would rely on ASCO/CAP guidelines on this. IHC testing remains the most validated tool at this time. I would favor repeating Her 2 testing on recurrent or metastatic site to address some of the discrepancies.

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Medical Oncology · Cancer Care Specialists/Renown Oncology/UNR
Answered on

HercepTest™ mAb pharmDx (Dako Omnis, GE001) picks up additional 10% Her2 low compared to Ventana PATHWAY anti-HER-2/neu (4B5). The latter is used more commonly.

Rüschoff et al., PMID 35970977

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