- Title
- p-STAT3 in luminal breast cancer: Integrated RNA-protein pooled analysis and results from the BIG 2-98 phase III trial
- Creator
- Sonnenblick, Amir; Salgado, Roberto; Crown, John; Viale, Giuseppe; Daly, Laura; Javdan, Bahar; Fujisawa, Sho; de Azambuja, Evandro; Lieveke, Ameye; Piccart, Martine; Bromberg, Jacqueline; Sotirou, Christos; Brohee, Sylvain; Zahavi, Tamar; Peretz, Tamar; van den Eynden, Gert; Rouas, Ghizlaine; Salmon, Asher; Francis, Prudence A.; Di Leo, Angelo
- Relation
- NHMRC.351164 http://purl.org/au-research/grants/nhmrc/351164
- Relation
- International Journal of Oncology Vol. 52, Issue 2, p. 424-432
- Publisher Link
- http://dx.doi.org/10.3892/ijo.2017.4212
- Publisher
- Spandidos Publications
- Resource Type
- journal article
- Date
- 2018
- Description
- 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.
- Subject
- signal transducer and activator of transcription 3; tyrosine phosphorylation; prognostic marker; adjuvant; chemotherapy; breast cancer; estrogen receptor; luminal cancer
- Identifier
- http://hdl.handle.net/1959.13/1387588
- Identifier
- uon:32634
- Identifier
- ISSN:1791-2423
- Language
- eng
- Full Text
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