In the present study, in order to investigate the role of signal transducer and activator of transcription 3 (STAT3) in estrogen receptor (ER)-positive breast cancer prognosis, we evaluated the phosphorylated STAT3 (p-STAT3) status and investigated its effect on the outcome in a pooled analysis and in a large prospective adjuvant trial. By using the TCGA repository, we developed gene signatures that reflected the level of p-STAT3. Using pooled analysis of the expression data from luminal breast cancer patients, we assessed the effects of the p-STAT3 expression signature on prognosis. We further validated the p-STAT3 prognostic effect using immunohistochemistry (IHC) and immunofluorescence staining of p-STAT3 tissue microarrays from a large randomised prospective trial. Our analysis demonstrated that p-STAT3 expression was elevated in luminal A-type breast cancer (Kruskal-Wallis test, P<10e-10) and was significantly associated with a good prognosis (log-rank, P<10e-10). Notably, the p-STAT3 expression signature identified patients with a good prognosis irrespective of the luminal subtype (log-rank: luminal A, P=0.026; luminal B, P=0.006). p-STAT3 staining by IHC in the stroma or tumour was detected in 174 out of 610 ER-positive samples (28.5%) from the BIG 2-98 randomised trial. With a median follow-up of 10.1 years, p-STAT3 was associated with a reduced risk of recurrence in ER-positive/HER2-negative breast cancer (Cox univariate HR, 0.66; 95% CI, 0.44-0.98; P=0.04). On the whole, our data indicate that p-STAT3 is associated with an improved outcome in ER-positive breast cancer.
P-STAT3 in luminal breast cancer: Integrated RNA-protein pooled analysis and results from the BIG 2-98 phase III trial / A. Sonnenblick, R. Salgado, S. Brohée, T. Zahavi, T. Peretz, G. Van Den Eynden, G. Rouas, A. Salmon, P.A. Francis, A. Di Leo, J.P.A. Crown, G. Viale, L. Daly, B. Javdan, S. Fujisawa, E. De Azambuja, A. Lieveke, M.J. Piccart, J.F. Bromberg, C. Sotiriou. - In: INTERNATIONAL JOURNAL OF ONCOLOGY. - ISSN 1019-6439. - 52:2(2018), pp. 424-432.
|Titolo:||P-STAT3 in luminal breast cancer: Integrated RNA-protein pooled analysis and results from the BIG 2-98 phase III trial|
|Parole Chiave:||Adjuvant; Breast cancer; Chemotherapy; Estrogen receptor; Luminal cancer; Prognostic marker; Signal transducer and activator of transcription 3; Tyrosine phosphorylation; Adenocarcinoma; Aged; Anthracyclines; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Breast Neoplasms; Chemotherapy, Adjuvant; Disease-Free Survival; Female; Humans; Kaplan-Meier Estimate; Middle Aged; Phosphorylation; Prognosis; Receptors, Estrogen; STAT3 Transcription Factor; Taxoids; Transcriptome; Oncology; Cancer Research|
|Settore Scientifico Disciplinare:||Settore MED/08 - Anatomia Patologica|
|Data di pubblicazione:||2018|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.3892/ijo.2017.4212|
|Appare nelle tipologie:||01 - Articolo su periodico|