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

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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)424-432
Number of pages9
JournalInternational Journal of Oncology
Volume52
Issue number2
DOIs
Publication statusPublished - Feb 1 2018

Keywords

  • Adjuvant
  • Breast cancer
  • Chemotherapy
  • Estrogen receptor
  • Luminal cancer
  • Prognostic marker
  • Signal transducer and activator of transcription 3
  • Tyrosine phosphorylation

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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