Posted on Nov 16, 2022

ERBB2 mRNA expression in HER2-low breast cancer

X. Teng1, X. Li2, S. Xu1, J. Zhang1, Y. Bai1, X. Ba1, Z. Wu1, S. Liu3.
1The First Affiliated Hospital- Zhejiang University School of Medicine, pathology, hangzhou, China.
2Shuwen Biotech Co. Ltd., Research Department, Hangzhou, China.
3Shuwen Guanz Diagnostic Laboratories Co. Ltd., Diagnostic Laboratories, Daqing, China.

Trastuzumab deruxtecan (or T-DXd), is an antibody-drug conjugate that delivers chemotherapy agents directly to cancer cells. Recent findings from the DESTINY-Breast04 trial have shown that this targeted therapy improves survival for patients with HER2-low metastatic breast cancer. This means expanded therapy to a new population of patients and the establishment of a new standard of care. HER2-low tumours are historically difficult to treat with varied prognosis and treatment response. Trastuzumab deruxtecan marks a new era of treatment for this type of breast cancer.

However, traditional immunohistochemistry (IHC) methods may not offer precise differentiation between HER2-negative and HER2-low tumours. This could bedue to human differences in interpretation for example. Some patients who may benefit from this new life-extending treatment may not be picked up using IHC and therefore will not have access to it.

The ability to precisely define which breast cancers are HER2-low would improve personalization of treatment, and open access to new therapies such as trastuzumab deruxtecan.

The study, what did the team do?

The level of ERBB2 in breast cancer specimens, collected during surgery, was assessed by three pathologists. ERBB2 is an expression of human epidermal growth factor receptor 2 or HER2.

The pathologists used ICH and FISH (fluorescence in situ hybridization). FISH is a laboratory technique used to detect and locate a specific DNA sequence on a chromosome.

The results from the three pathologists were correlated to check for consistency, and then compared to results using the MammaTyper® quantitative real-time polymerase chain reaction (qRT-PCR) kit.

What did they find?

The researchers analysed 177 breast cancer samples. Comparison between the three pathologists showed excellent reliability.

Among these 177 cases:

  • 42 cases were unanimously rated as HER2-negative
  • 115 cases as HER2-low
  • 20 cases were evaluated inconsistently for HER2-negativeor HER2-low by three pathologists.

Of the cases rated as HER2-negative, just over 45% showed ERBB2-low expression when analysed with MammaTyper®. Meaning they had potentially been misclassified. There was also an indication that IHC methods are not accurate enough at judging the expression of ERBB2 at the ‘boundary value’: between HER2-negative and HER2-low.

In real-world terms this may mean that some patients may not be given accurate enough results and therefore may not be offered some of the newer targeted therapies.

What does this mean? Compared with IHC/FISH, MammaTyper® qRT-PCR assay may be a promising alternative for actual detection of ERBB2 expression. This will help in better definition of HER2-low breast cancer.