Abstract 27P
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
HER2-low | HER2-zero | p-value | |
BL1 | 14 (44%) | 13 (43%) | |
BL2 | 2 (6%) | 3 (10%) | |
LAR | 11 (34%) | 1 (3%) | 0.00017 |
M | 1 (3%) | 9 (30%) | |
N/A | 4 (13%) | 4 (13%) |
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.
Resources from the same session
228P - Real-world data on dose adjustment of cabozantinib in advanced renal cell carcinoma
Presenter: Hemavathi Baskarane
Session: Poster Display
Resources:
Abstract
229P - The application of diffusion kurtosis imaging in predicting muscle invasion of bladder cancer: A comparison with conventional DWI
Presenter: Shuai Jiang
Session: Poster Display
Resources:
Abstract
230P - Oncological outcomes between partial cystectomy and radical cystectomy in solitary muscle invasive bladder cancer with downgraded T stage
Presenter: Ming Wei Hsu
Session: Poster Display
Resources:
Abstract
231P - BMI-predicted progression-free survival after pembrolizumab therapy for urothelial cancer: Asian version of BMI classification is suitable for Asian patients
Presenter: mirii harada
Session: Poster Display
Resources:
Abstract
232P - The immunosuppressive features of the 20S Proteasome β-subunit gene family in von Hippel-Lindau (VHL)-mutated clear cell renal cell carcinoma (ccRCC): A TCGA-based bioinformatics study
Presenter: Saja Alzghoul
Session: Poster Display
Resources:
Abstract
233P - The crosstalk between PBRM1 loss and tumor immune microenvironment (TIME) of clear cell renal cell carcinoma (ccRCC): A possible interconnection to immunotherapy response
Presenter: Ahmed Al Sharie
Session: Poster Display
Resources:
Abstract
235P - Do FGFR2 and 3 proteins have a role in the prognosis of urothelial bladder carcinoma?
Presenter: Alshimaa Al Hanafy
Session: Poster Display
Resources:
Abstract
236P - The effects of chemotherapy on body composition in patients with advanced urothelial carcinoma
Presenter: KOSUKE KITAMURA
Session: Poster Display
Resources:
Abstract
237P - Real-world analysis of adjuvant nivolumab in resected urothelial cancer: A single institute study in Taiwanese patients
Presenter: Mu-Hsin Chang
Session: Poster Display
Resources:
Abstract
238P - Enfortumab-vedotin for metastatic urothelial carcinoma refractory to platinum-based chemotherapy and immune checkpoint inhibitors: A single institution experience
Presenter: Yuki Endo
Session: Poster Display
Resources:
Abstract