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Prognostic Significance of Transforming Growth Factor ß Receptor II in Estrogen Receptor-Negative Breast Cancer Patients

¹ Robert Bosch Hospital, Department of Clinical Chemistry, Stuttgart; ² Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart; ³ Department of Mathematics, University of Stuttgart, Stuttgart; and ⁴ Department of Hematology and Oncology, University Medical Center, Marburg, Germany

Purpose: The role of transforming growth factor ß (TGF-ß) in breast cancer is ambiguous; it can display both tumor suppressing and enhancing effects. Activation of the TGF-ß signal transduction system is subject to hormonal regulation. This study was conducted to further analyze the role of TGF-ß receptors in breast cancer and to evaluate their significance as prognostic markers.

Experimental Design: Expression of TGF-ß receptor I (TßRI) and TGFß receptor II (TßRII) was retrospectively analyzed by immunohistochemistry in 246 breast cancer patients.

Results: Expression of TßRI was strongly correlated with tumor size (P < 0.001) and nodal status (P = 0.012) but only weakly with overall survival (P = 0.056). In contrast, TßRII was prognostic for overall survival in univariate analysis (P = 0.0370). In estrogen receptor (ER) -negative patients TßRII expression was correlated with highly reduced overall survival (P = 0.0083). In multivariate analysis TßRII proved to be an independent and highly significant prognostic marker with a hazard ratio of 6.8. Simultaneous loss of both ER and TßRII was associated with longer overall survival times comparable with those of ER-positive patients.

Conclusions: The results of this exploratory study show that TßRII is an independent, highly significant prognostic indicator for overall survival in ER-negative patients. In addition our results are supportive of a mechanism of breast cancer progression in which a selective loss of the tumor inhibitory action of TGFß takes place, whereas tumor- promoting aspects remain intact.

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