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Updated: Mar 18, 2026
Systems Biology of Metabolic Regulation by Estrogen Receptor Signaling in Breast Cancer
Published on: March 17, 2016
A whole-genome sequence and transcriptome perspective on HER2-positive breast cancers
Anthony Ferrari1, Anne Vincent-Salomon2, Xavier Pivot3
1Synergie Lyon Cancer, Plateforme de bioinformatique 'Gilles Thomas' Centre Léon Bérard, 28 rue Laënnec, 69008 Lyon, France.
Abstract:
HER2-positive breast cancer has long proven to be a clinically distinct class of breast cancers for which several targeted therapies are now available. However, resistance to the treatment associated with specific gene expressions or mutations has been observed, revealing the underlying diversity of these cancers. Therefore, understanding the full extent of the HER2-positive disease heterogeneity still remains challenging. Here we carry out an in-depth genomic characterization of 64 HER2-positive breast tumour genomes that exhibit four subgroups, based on the expression data, with distinctive genomic features in terms of somatic mutations, copy-number changes or structural variations. The results suggest that, despite being clinically defined by a specific gene amplification, HER2-positive tumours melt into the whole luminal-basal breast cancer spectrum rather than standing apart. The results also lead to a refined ERBB2 amplicon of 106 kb and show that several cases of amplifications are compatible with a breakage-fusion-bridge mechanism.
Insights
HER2-positive breast cancer shows significant genomic diversity. This study reveals four subgroups with distinct features, suggesting it’s part of the broader luminal-basal spectrum, not a separate entity.
Area of Science:
- Genomics
- Oncology
- Breast Cancer Research
Background:
- HER2-positive breast cancer is a distinct subtype with available targeted therapies.
- Treatment resistance highlights the heterogeneity and complexity of HER2-positive breast cancers.
- Understanding this heterogeneity is crucial for effective treatment strategies.
Purpose of the Study:
- To perform in-depth genomic characterization of HER2-positive breast tumors.
- To identify and define subgroups within HER2-positive breast cancer based on genomic features.
- To explore the relationship between HER2-positive breast cancer and the broader luminal-basal spectrum.
Main Methods:
- Genomic characterization of 64 HER2-positive breast tumor genomes.
- Analysis of somatic mutations, copy-number changes, and structural variations.
- Subgroup identification based on gene expression data.
Main Results:
- Identification of four distinct subgroups within HER2-positive breast tumors.
- These subgroups exhibit unique genomic features, including mutations and copy-number alterations.
- HER2-positive tumors integrate into the luminal-basal breast cancer spectrum, challenging their distinct classification.
Conclusions:
- HER2-positive breast cancer is more heterogeneous than previously thought, with distinct genomic subgroups.
- The findings suggest HER2-positive breast cancer is part of a continuum with luminal-basal breast cancers.
- A refined ERBB2 amplicon of 106 kb was identified, with amplifications potentially linked to a breakage-fusion-bridge mechanism.
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