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Updated: May 5, 2026
Building Up a High-throughput Screening Platform to Assess the Heterogeneity of HER2 Gene Amplification in Breast Cancers
Published on: December 5, 2017
Clinical and molecular characteristics of HER2-low triple-negative breast cancer: insights from multi-omics analysis
Yinlong Yang1, Liangwei Pan1, Wenzhe Zhou1
1Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Fudan University, Shanghai Medical College, Shanghai, China.
Background:
The emergence of novel human epidermal growth factor receptor 2 (HER2)-targeting drugs has provided a new therapeutic option for HER2-low triple-negative breast cancer (TNBC) patients who had limited treatment choices previously. However, the biological implications and prognostic significance of HER2-low status in TNBC are still not fully appreciated.
Methods:
Utilizing a single-center multi-omics cohort of TNBC patients that includes whole exome sequencing and RNA sequencing data, this study aims to explore the clinical and molecular characteristics between HER2-low and HER2-0 TNBC.
Results:
The study comprised 207 patients with HER2-low TNBC and 153 patients with HER2-0 TNBC. Findings revealed that HER2-low tumors exhibited lower tumor grade, more nodal involvement and lower Ki-67 index compared to HER2-0 tumors. Additionally, HER2-low TNBC were associated with more mutations in PIK3CA and its corresponding pathways, a more prominent clock-like mutation signature, along with activation of androgen receptor (AR)-related pathways and fatty acid metabolism. While HER2-low status did not significantly influence recurrence-free survival (RFS) across the entire study population, HER2-low patients showed significant better RFS compared to HER2-0 patients within the luminal androgen receptor (LAR) subtype. This distinction was also evident at molecular level.
Conclusion:
HER2-low TNBC demonstrated unique clinical, transcriptomic and genomic characteristics when contrasted with HER2-0 TNBC. In the LAR subtype, a clear molecular and prognostic discrepancy between HER2-0 and HER2-low tumors was identified.
Insights
HER2-low triple-negative breast cancer (TNBC) shows distinct molecular features compared to HER2-0 TNBC. HER2-low status is linked to better recurrence-free survival in the Luminal Androgen Receptor (LAR) subtype.
Area of Science:
- Oncology
- Genomics
- Molecular Biology
Background:
- Novel HER2-targeting drugs offer new options for HER2-low triple-negative breast cancer (TNBC).
- The biological and prognostic implications of HER2-low status in TNBC require further elucidation.
Purpose of the Study:
- To investigate the clinical and molecular differences between HER2-low and HER2-0 TNBC.
- To assess the prognostic significance of HER2-low status in TNBC.
Main Methods:
- Multi-omics analysis (whole exome sequencing, RNA sequencing) of 360 TNBC patients.
- Comparison of clinical, genomic, and transcriptomic data between HER2-low (n=207) and HER2-0 (n=153) cohorts.
Main Results:
- HER2-low TNBC exhibited lower grade, more nodal involvement, and lower Ki-67 index than HER2-0 TNBC.
- HER2-low tumors showed increased PIK3CA mutations, a clock-like mutation signature, and activated AR pathways and fatty acid metabolism.
- HER2-low status did not impact overall recurrence-free survival (RFS) but improved RFS in the Luminal Androgen Receptor (LAR) subtype.
Conclusions:
- HER2-low TNBC possesses unique clinical, transcriptomic, and genomic profiles compared to HER2-0 TNBC.
- A significant molecular and prognostic difference exists between HER2-0 and HER2-low tumors within the LAR subtype.
