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Journal of Translational Medicine
Published in: Journal of Translational Medicine 1/2012

Open Access 01-12-2012 | Research

HER2 and TOP2A in high-risk early breast cancer patients treated with adjuvant epirubicin-based dose-dense sequential chemotherapy

Authors: George Fountzilas, Christos Valavanis, Vassiliki Kotoula, Anastasia G Eleftheraki, Konstantine T Kalogeras, Olympia Tzaida, Anna Batistatou, Ralf Kronenwett, Ralph M Wirtz, Mattheos Bobos, Eleni Timotheadou, Nikolaos Soupos, George Pentheroudakis, Helen Gogas, Dimitrios Vlachodimitropoulos, Genovefa Polychronidou, Gerasimos Aravantinos, Angelos Koutras, Christos Christodoulou, Dimitrios Pectasides, Petroula Arapantoni

Published in: Journal of Translational Medicine | Issue 1/2012

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Abstract

Background

HER2 and TOP2A parameters (gene status, mRNA and protein expression) have individually been associated with the outcome of patients treated with anthracyclines. The aim of this study was to comprehensively evaluate the prognostic/predictive significance of the above parameters in early, high-risk breast cancer patients treated with epirubicin-based, dose-dense sequential adjuvant chemotherapy.

Methods

In a series of 352 breast carcinoma tissues from patients that had been post-operatively treated with epirubicin-CMF with or without paclitaxel, we assessed HER2 and TOP2A gene status (chromogenic in situ hybridization), mRNA expression (quantitative reverse transcription PCR), as well as HER2 and TopoIIa protein expression (immunohistochemistry).

Results

HER2 and TOP2A amplification did not share the same effects on their downstream molecules, with consistent patterns observed in HER2 mRNA and protein expression according to HER2 amplification (all parameters strongly inter-related, p values < 0.001), but inconsistent patterns in the case of TOP2A. TOP2A gene amplification (7% of all cases) was not related to TOP2A mRNA and TopoIIa protein expression, while TOP2A mRNA and TopoIIa protein were strongly related to each other (p < 0.001). Hence, TOP2A amplified tumors did not correspond to tumors with high TOP2A mRNA or TopoIIa protein expression, while the latter were characterized by high Ki67 scores (p = 0.003 and p < 0.001, respectively). Multivariate analysis adjusted for nodal involvement, hormone receptor status, Ki67 score and HER2/TOP2A parameters revealed HER2/TOP2A co-amplification (21.2% of HER2 amplified tumors) as an independent favorable prognostic factor for DFS (HR = 0.13, 95% CI: 0.02-0.96, p = 0.046); in contrast, increased HER2/TOP2A mRNA co-expression was identified as an independent adverse prognostic factor for both DFS (HR = 2.41, 95% CI: 1.31-4.42, p = 0.005) and OS (HR = 2.83, 95% CI: 1.42-5.63, p = 0.003), while high TOP2A mRNA expression was an independent adverse prognostic factor for OS (HR = 2.06, 95% CI: 1.23-3.46, p = 0.006). None of the parameters tested was associated with response to paclitaxel.

Conclusions

This study confirms the favorable prognostic value of HER2/TOP2A co-amplification and the adverse prognostic value of high TOP2A mRNA expression extending it to the adjuvant treatment setting in early high-risk breast cancer. The strong adverse prognostic impact of high HER2/TOP2A mRNA co-expression needs further validation in studies designed to evaluate markers predictive for anthracyclines.

Trial registration

Australian New Zealand Clinical Trials Registry ACTRN12611000506​998.
Appendix
Available only for authorised users
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Metadata
Title
HER2 and TOP2A in high-risk early breast cancer patients treated with adjuvant epirubicin-based dose-dense sequential chemotherapy
Authors
George Fountzilas
Christos Valavanis
Vassiliki Kotoula
Anastasia G Eleftheraki
Konstantine T Kalogeras
Olympia Tzaida
Anna Batistatou
Ralf Kronenwett
Ralph M Wirtz
Mattheos Bobos
Eleni Timotheadou
Nikolaos Soupos
George Pentheroudakis
Helen Gogas
Dimitrios Vlachodimitropoulos
Genovefa Polychronidou
Gerasimos Aravantinos
Angelos Koutras
Christos Christodoulou
Dimitrios Pectasides
Petroula Arapantoni
Publication date
01-12-2012
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2012
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/1479-5876-10-10

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Journal of Translational Medicine 1/2012 Go to the issue

Research

High-Intensity Interval Resistance Training (HIRT) influences resting energy expenditure and respiratory ratio in non-dieting individuals

Research

JAK-STAT and AKT pathway-coupled genes in erythroid progenitor cells through ontogeny

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IRF5 gene polymorphisms in melanoma

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After insufficient radiofrequency ablation, tumor-associated endothelial cells exhibit enhanced angiogenesis and promote invasiveness of residual hepatocellular carcinoma

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GOLPH3 overexpression correlates with tumor progression and poor prognosis in patients with clinically N0 oral tongue cancer

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Hematopoietic stem cell transplantation induces immunologic tolerance in renal transplant patients via modulation of inflammatory and repair processes
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Obesity Clinical Trial Summary

At a glance: The STEP trials

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A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

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Year in Review: Valvular heart disease

Valvular Heart Disease Video

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Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

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Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

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Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

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New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

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