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The prognostic role of TGF-β signaling pathway in breast cancer patients
Departments of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
Departments of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
Departments of Molecular Cell Biology and Centre for Biomedical Genetics, Leiden University Medical Center, Leiden, The Netherlands.
Departments of Medical Statistics, Leiden University Medical Center, Leiden, The Netherlands.
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2013 (English)In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 24, no 2, 384-390 p.Article in journal (Refereed) Published
Abstract [en]

Background

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.

Patients and methods

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.

Results

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.

Conclusions

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.

Place, publisher, year, edition, pages
2013. Vol. 24, no 2, 384-390 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-193356DOI: 10.1093/annonc/mds333ISI: 000314057100018PubMedID: 23022998OAI: oai:DiVA.org:uu-193356DiVA: diva2:602139
Available from: 2013-01-31 Created: 2013-01-31 Last updated: 2017-12-06Bibliographically approved

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