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Breast Cancer Research
Published in: Breast Cancer Research 1/2018

Open Access 01-12-2018 | Research Article

HER2 is not a cancer subtype but rather a pan-cancer event and is highly enriched in AR-driven breast tumors

Authors: Anneleen Daemen, Gerard Manning

Published in: Breast Cancer Research | Issue 1/2018

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Abstract

Background

Approximately one in five breast cancers are driven by amplification and overexpression of the human epidermal growth factor receptor 2 (HER2) receptor kinase, and HER2-enriched (HER2E) is one of four major transcriptional subtypes of breast cancer. We set out to understand the genomics of HER2 amplification independent of subtype, and the underlying drivers and biology of HER2E tumors.

Methods

We investigated published genomic data from 3155 breast tumors and 5391 non-breast tumors.

Results

HER2 amplification is a distinct driver event seen in all breast cancer subtypes, rather than a subtype marker, with major characteristics restricted to amplification and overexpression of HER2 and neighboring genes. The HER2E subtype has a distinctive transcriptional landscape independent of HER2A that reflects androgen receptor signaling as replacement for estrogen receptor (ER)-driven tumorigenesis. HER2 amplification is also an event in 1.8% of non-breast tumors.

Conclusions

These discoveries reveal therapeutic opportunities for combining anti-HER2 therapy with anti-androgen agents in breast cancer, and highlight the potential for broader therapeutic use of HER2 inhibitors.
Appendix
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Metadata
Title
HER2 is not a cancer subtype but rather a pan-cancer event and is highly enriched in AR-driven breast tumors
Authors
Anneleen Daemen
Gerard Manning
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 1/2018
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/s13058-018-0933-y

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