27P - The biological characteristics of HER2-low in TNBC using mRNA profiling and molecular subtypes

Background

HER2-low breast cancers are defined as having an immunohistochemical (IHC) score of 1+, or 2+ with nonamplified in-situ hybridization (ISH). The biological features of HER2-low-expressing triple-negative breast cancers (TNBC) remain unclear. This study aimed to reveal the TNBC molecular subtypes with both HER2-low and HER2-zero using mRNA profiling and identify the biological characteristics of HER2-low in TNBC.

Methods

We analyzed 64 cases of TNBCs collected from four medical centers. Molecular subtypes of TNBC were identified, and comprehensive expression analysis was performed. The correlation between mRNA expression and HER2 expression in protein IHC was also analyzed.

Results

Of the 64 cases, 30 had HER2-zero, and 32 had HER2-low-positive. Luminal androgen receptor (LAR) subtype was more common in the HER2-low group (P=0.0017). Table: 27P

TNBC molecular subtype compared with HER2-low and HER2-zero

The HER2-low group had significantly higher ERBB2 expression than the HER2-zero group (p=0.05). In 20% of the HER2-zero group, HER2 expression was detected at the mRNA expression level. When performing clustering analysis between HER2-low and HER2-zero, among the top 10 genes highly expressed in HER2-low, genes highly expressed in hormone-dependent tumors such as FOXA1 and genes involved in metabolic process were found. Interestingly, somatic BRCA1 expression was significantly higher in the HER2-zero group.

Conclusions

The HER2-low group had molecular features that were distinct from the HER2-zero group and were more similar to the LAR subtype. Evaluating HER2 expression by mRNA may identify HER2-low breast cancers that cannot be identified at the protein level in IHC, which may allow for more patients with TNBC to receive effective anti-HER2 drugs. However, further studies are needed to confirm these findings.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Oncocyte.

Disclosure

N. Hayashi: Financial Interests, Personal, Speaker’s Bureau: Eli Lily, AstraZeneca, Taiho, Eizai, Novartis, Pfizer, Chugai; Financial Interests, Personal, Research Funding: AstraZeneca, MSD, Konica Minolta Japan, Chugai. S. Nakamura: Financial Interests, Institutional, Funding: AstraZeneca, Daiichi Sankyo; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Daiichi Sankyo, Chugai. R. Seitz, D. Hout: Other, Personal, Member: Oncocyte. N.T. Ueno: Financial Interests, Personal, Advisory Board: Daiichi Sankyo. H. Masuda: Financial Interests, Personal, Speaker’s Bureau: Sysmex, Eli Lily, Pfizer, Chugai. All other authors have declared no conflicts of interest.