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
613P - Differences in the interactions with pharmaceutical companies between medical oncologists and infectious diseases physicians
Presenter: Hui Ling Yeoh
Session: Poster Display
Resources:
Abstract
614P - The role of PD-L1 expression in prognosis of osteosarcoma patients: A systematic review and meta-analysis
Presenter: Alexander Purnomo
Session: Poster Display
Resources:
Abstract
615P - Pulmonary resectable metastases of osteosarcoma with apatinib and chemotherapy (PROACH): An open-label, single-arm phase II clinical trial
Presenter: Qiyuan Bao
Session: Poster Display
Resources:
Abstract
616P - Incidence of cardiotoxicity after high cumulative dose of anthracyclines in adult patients with advanced soft tissue sarcomas: A systematic review and meta-analysis
Presenter: Paula Franco
Session: Poster Display
Resources:
Abstract
617P - The risk of acute myeloid leukaemia in patients with Ewing's sarcoma and trend analysis: A SEER-based study 2000-2020
Presenter: Mohamed Abdalla
Session: Poster Display
Resources:
Abstract
618P - Adult renal Ewing’s sarcoma/primitive neuroectodermal tumor: A 20-year retrospective review of molecular histopathological profiles, and clinical outcomes
Presenter: Josh Thomas Georgy
Session: Poster Display
Resources:
Abstract
619P - Single-cell and bulk RNA-seq analyses decode the renal microenvironment induced by polystyrene microplastics in mice receiving high-fat diet
Presenter: Wangrui Liu
Session: Poster Display
Resources:
Abstract
620P - A unique circulating microRNA pairs signature serves as a superior tool for early diagnosis of pan-cancer
Presenter: Dongyu Li
Session: Poster Display
Resources:
Abstract
621P - Effective identification of primary liver cancer from cirrhosis or chronic hepatitis virus infection using eight methylated plasma DNA markers: Marker discovery, phase I pilot, and phase II clinical validation
Presenter: Tian Yang
Session: Poster Display
Resources:
Abstract
622P - A prognostic and immune infiltration analysis of CCL26 in pan-cancer
Presenter: Mengyue Li
Session: Poster Display
Resources:
Abstract