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Breast Cancer Research
Published in: Breast Cancer Research 2/2012

Open Access 01-04-2012 | Research article

ER and HER2 expression are positively correlated in HER2 non-overexpressing breast cancer

Authors: Isabel Pinhel, Margaret Hills, Suzanne Drury, Janine Salter, Georges Sumo, Roger A'Hern, Judith M Bliss, Ivana Sestak, Jack Cuzick, Peter Barrett-Lee, Adrian Harris, Mitch Dowsett, the NCRI Adjuvant Breast Cancer Trial Management Group

Published in: Breast Cancer Research | Issue 2/2012

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Abstract

Introduction

Estrogen receptor-α (ER) and human epidermal growth factor receptor 2 (HER2) positivity are inversely correlated by standard criteria. However, we investigated the quantitative relation between ER and HER2 expression at both RNA and protein levels in HER2+ve and HER2-ve breast carcinomas.

Methods

ER and HER2 levels were assessed with immunohistochemistry (IHC) and (for HER2) fluorescent in situ hybridization (FISH) and by quantitative reverse transcription-polymerase chain reaction (q-RT-PCR) in formalin-fixed primary breast cancers from 448 patients in the National Cancer Research Institute (NCRI) Adjuvant Breast Cancer Trial (ABC) tamoxifen-only arm. Relations at the RNA level were assessed in 1,139 TransATAC tumors.

Results

ER and HER2 RNA levels were negatively correlated as expected in HER2+ve (IHC 3+ and/or FISH-amplified) tumors (r = -0.45; P = 0.0028). However, in HER2-ve tumors (ER+ve and ER-ve combined), a significant positive correlation was found (r = 0.43; P < 0.0001), HER2 RNA levels being 1.74-fold higher in ER+ve versus ER-ve tumors. This correlation was maintained in the ER+veHER2-ve subgroup (r = 0.24; P = 0.0023) and confirmed in this subgroup in 1,139 TransATAC tumours (r = 0.25; P < 0.0001). The positive relation extended to IHC-detected ER in ABC: mean ± 95% confidence interval (CI) H-scores were 90 ± 19 and 134 ± 19 for 0 and 1+ HER2 IHC categories, respectively (P = 0.0013). A trend toward lower relapse-free survival (RFS) was observed in patients with the lowest levels of ER and HER2 RNA levels within the ER+veHER2-ve subgroup both for ABC and TransATAC cohorts.

Conclusions

ER and HER2 expression is positively correlated in HER2-ve tumors. The distinction between HER2+ve and HER2-ve is greater in ER-ve than in ER+ve tumors. These findings are important to consider in clinical trials of anti-HER2 and anti-endocrine therapy in HER2-ve disease.

Trial Registration

Clinical trial identifier: ISRCTN31514446.
Appendix
Available only for authorised users
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Metadata
Title
ER and HER2 expression are positively correlated in HER2 non-overexpressing breast cancer
Authors
Isabel Pinhel
Margaret Hills
Suzanne Drury
Janine Salter
Georges Sumo
Roger A'Hern
Judith M Bliss
Ivana Sestak
Jack Cuzick
Peter Barrett-Lee
Adrian Harris
Mitch Dowsett
the NCRI Adjuvant Breast Cancer Trial Management Group
Publication date
01-04-2012
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 2/2012
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/bcr3145

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