A Comparison Between Immunohistochemistry and mRNA Expression to Identify Human Epidermal Growth Factor Receptor 2-Low Breast Cancer

Breast cancers (BCs) with low levels of human epidermal growth factor receptor 2 (HER2) expression (HER2-low) have become a targetable subset because of novel antibody-drug conjugates. HER2 immunohistochemistry (IHC) is the recommended assay for HER2 classification but is associated with limited interobserver agreement concerning HER2-low identification. To investigate whether mRNA expression quantified via quantitative reverse transcription-polymerase chain reaction (RT-qPCR) could serve as a valuable complementary and more objective method to identify HER2-low BCs. We selected all cases from a previously published interobserver study, which included 105 needle biopsies from HER2 nonamplified BC cases. HER2 IHC was evaluated by 16 pathologists. For the current study, mRNA was extracted from microdissected invasive tumor cells. RT-qPCR was performed for quantitative evaluation of HER2, using the cutoff values of the MammaTyper assay. We compared the mRNA expression levels with the IHC scores of the majority agreement (IHC 0, IHC >0,