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Annals of Oncology Advance Access published online on November 13, 2009
Annals of Oncology, doi:10.1093/annonc/mdp518
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© The Author 2009. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org

Absence of transforming growth factor-β type II receptor is associated with poorer prognosis in HER2-negative breast tumours

C. E. Paiva1,{dagger}, S. A. Drigo2,{dagger}, F. E. Rosa2, F. A. Moraes Neto3, J. R. F. Caldeira4, F. A. Soares5, M. A. C. Domingues6 and S. R. Rogatto2,*

1 Oncological and Hemato-oncological Center, São Paulo State University, Botucatu
2 NeoGene Laboratory, Department of Urology, São Paulo State University, Botucatu and A. C. Camargo Cancer Treatment and Research Center
3 Department of Pathology
4 Department of Senology, Amaral Carvalho Hospital, Jaú
5 Department of Pathology, A. C. Camargo Cancer Treatment and Research Center
6 Department of Pathology, São Paulo State University, Botucatu, São Paulo, Brazil

* Correspondence to: Dr S. R. Rogatto, NeoGene Laboratory, Fundação Antonio Prudente, Hospital A.C. Camargo, Rua Professor Antonio Prudente, 211, Liberdade, São Paulo 01509-010, Brazil. Tel: +55-11-21895163; Fax: +55-11-21895163; E-mail: rogatto{at}fmb.unesp.br

Background: The clinical relevance of transforming growth factor-beta (TGF-β)-signalling pathway in breast carcinomas (BCs) remained elusive. This study aimed to evaluate the prognostic value of TGF-β1 and transforming growth factor-beta type II receptor (TGF-βRII) expression levels in tumour cells and their association with the established biomarkers in BC.

Patients and methods: In 324 BC from patients with long-term follow-up, the TGF-β1 and TGF-βRII transcript and protein expression levels were assessed.

Results: TGF-β1 and TGF-βRII down-expression was significantly associated with BC. Negative TGF-β1 and TGF-βRII protein status was associated with the development of distant metastasis (P = 0.003 and P = 0.029, respectively). In multivariate analysis, TGF-β1-positive tumours were associated with increased disease-free survival (DFS) [hazard ratio (HR) = 0.489, P = 0.003]. TGF-βRII positivity was an independent prognostic factor for DFS (HR = 0.439, P = 0.001) and overall survival (OS) (HR = 0.409, P = 0.003) in human epidermal growth factor receptor-2 (HER2)-negative patients. Absence of TGF-β1 and TGF-βRII proteins in breast tumour cells was significantly associated with metastasis development.

Conclusions: To the best of our knowledge, this is the first report indicating the relevance of HER2 status in discriminating TGF-βRII as a prognostic marker for DFS and OS in human BC. These data indicate that TGF-βRII protein analysis in tumour cells could be introduced in clinical practice as additional prognostic biomarker in HER2-negative BC.

breast cancer, HER2, prognostic markers, TGF-β1, TGF-βRII

{dagger} Both authors have contributed equally.

Received for publication September 17, 2009. Accepted for publication October 6, 2009.


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