The prognostic role of TGF-β signaling pathway in breast cancer patients

The transforming growth factor-β (TGF-β) pathway has dual effects on tumor growth. Seemingly, discordant results have been published on the relation between TGF-β signaling markers and prognosis in breast cancer. Improved prognostic information for breast cancer patients might be obtained by assessi...

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Veröffentlicht in:Annals of oncology 2013-02, Vol.24 (2), p.384-390
Hauptverfasser: de Kruijf, E.M., Dekker, T.J.A., Hawinkels, L.J.A.C., Putter, H., Smit, V.T.H.B.M., Kroep, J.R., Kuppen, P.J.K., van de Velde, C.J.H., ten Dijke, P., Tollenaar, R.A.E.M., Mesker, W.E.
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Sprache:eng
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Zusammenfassung:The transforming growth factor-β (TGF-β) pathway has dual effects on tumor growth. Seemingly, discordant results have been published on the relation between TGF-β signaling markers and prognosis in breast cancer. Improved prognostic information for breast cancer patients might be obtained by assessing interactions among TGF-β signaling biomarkers. The expression of nuclear Smad4, nuclear phosphorylated-Smad2 (p-Smad2), and the membranous expression of TGF-β receptors I and II (TβRI and TβRII) was determined on a tissue microarray of 574 breast carcinomas. Tumors were stratified according to the Smad4 expression in combination with p-Smad2 expression or Smad4 in combination with the expression of both TGF-β receptors. Tumors with high expression of TβRII, TβRI and TβRII, and p-Smad2 (P = 0.018, 0.005, and 0.022, respectively), and low expression of Smad4 (P = 0.005) had an unfavorable prognosis concerning progression-free survival. Low Smad4 expression combined with high p-Smad2 expression or low expression of Smad4 combined with high expression of both TGF-β receptors displayed an increased hazard ratio of 3.04 [95% confidence interval (CI) 1.390–6.658] and 2.20 (95% CI 1.464–3.307), respectively, for disease relapse. Combining TGF-β biomarkers provides prognostic information for patients with stage I–III breast cancer. This can identify patients at increased risk for disease recurrence that might therefore be candidates for additional treatment.
ISSN:0923-7534
1569-8041
1569-8041
DOI:10.1093/annonc/mds333