p-STAT3 in luminal breast cancer: Integrated RNA-protein pooled analysis and results from the BIG 2-98 phase III trial

Sonnenblick,Amir; Sonnenblick,Amir; Salgado,Roberto; Salgado,Roberto; Brohée,Sylvain; Brohée,Sylvain; Zahavi,Tamar; Zahavi,Tamar; Peretz,Tamar; Peretz,Tamar; Van den Eynden,Gert; Van den Eynden,Gert; Rouas,Ghizlane; Rouas,Ghizlane; Salmon,Asher; Salmon,Asher; Francis,Prudence A.; Francis,Prudence A.; Di Leo,Angelo; Di Leo,Angelo; Crown,John P.A.; Crown,John P.A.; Viale,Giuseppe; Viale,Giuseppe; Daly,Laura; Daly,Laura; Javdan,Bahar; Javdan,Bahar; Fujisawa,Sho; Fujisawa,Sho; De Azambuja,Evandro; De Azambuja,Evandro; Lieveke,Ameye; Lieveke,Ameye; Piccart,Martine J.; Piccart,Martine J.; Bromberg,Jacqueline F.; Bromberg,Jacqueline F.; Sotiriou,Christos; Sotiriou,Christos

doi:10.3892/ijo.2017.4212

p-STAT3 in luminal breast cancer: Integrated RNA-protein pooled analysis and results from the BIG 2-98 phase III trial

Authors:
- Amir Sonnenblick
- Roberto Salgado
- Sylvain Brohée
- Tamar Zahavi
- Tamar Peretz
- Gert Van den Eynden
- Ghizlane Rouas
- Asher Salmon
- Prudence A. Francis
- Angelo Di Leo
- John P.A. Crown
- Giuseppe Viale
- Laura Daly
- Bahar Javdan
- Sho Fujisawa
- Evandro De Azambuja
- Ameye Lieveke
- Martine J. Piccart
- Jacqueline F. Bromberg
- Christos Sotiriou
View Affiliations

Affiliations: Sharett Institute of Oncology, Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel, Breast Cancer Translational Research Laboratory J.-C. Heuson, Institut Jules Bordet, Université Libre de Bruxelles, 1000 Brussels, Belgium, Peter MacCallum Cancer Centre, Melbourne VIC 3000, Victoria, on behalf of The Australian and New Zealand Breast Cancer Trials Group, Newcastle, NSW 2298, Australia, and International Breast Cancer Study Group, 3008 Bern, Switzerland, ‘Sandro Pitigliani’ Medical Oncology Department, Hospital of Prato, Istituto Toscano Tumori, 50139 Firenze, Prato, Italy, St. Vincet's University Hospital, Elm Park, on behalf of the Irish Clinical Oncology Research, Dublin 4, Ireland, Division of Pathology, European Institute of Oncology, 20146 Milano, Italy, Department of Medicine, Memorial Sloan Kettering Cancer Center (MSKCC), New York, NY 10065, USA
Published online on: November 27, 2017 https://doi.org/10.3892/ijo.2017.4212
Pages: 424-432

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Abstract

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.