Signal transducer and activator of transcription-5 activation and breast cancer prognosis

Abstract

Purpose: Transcription factor signal transducer and activator of transcription-5 (Stat5) promotes breast epithelial cell differentiation. We retrospectively analyzed whether levels of active Stat5 in breast cancer were linked to clinical outcome.

Materials and methods: Immunohistochemistry was used to detect active, tyrosine-phosphorylated Stat5 in paraffin-embedded breast cancer specimens from three archival tissue microarray materials A, B, and C. Material A included 19 healthy human breast tissues and a progression series of primary lymph node-negative, primary lymph node-positive, and metastatic breast cancer (n = 400). Materials B (n = 785) and C (n = 570) represented two independent arrays of unselected primary breast cancer specimens with clinical follow-up data.

Results: Material A demonstrated that Stat5 activation, but not Stat5 protein expression, was gradually lost during cancer progression, with detectable activation in 100% of healthy breast specimens compared with less than 20% of node-positive breast cancers and metastases. Stat5 activation in tumors of material B was associated with favorable prognosis. This observation was confirmed and extended in material C to include both breast cancer-specific survival and disease-free survival. Stat5 activation remained an independent prognostic marker after adjusting for patient age, tumor size, histological grade, estrogen receptor, progesterone receptor, and Her2/neu status by Cox multivariate analysis (hazard ratio, 2.0; P =.029). Stat5 activation was a particularly favorable marker in the lymph node-negative breast cancer subpopulation (hazard ratio, 7.5; P =.003).

Conclusion: In our study, active Stat5 distinguishes breast cancer patients with favorable prognosis, and may be a useful marker for selection of more individualized treatment, especially in localized disease. These findings require confirmation in a large prospective study.

 

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See also:

- Official Web Site: The Di Bella Method;

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- The Di Bella Method (A Fixed Part - Bromocriptine and/or Cabergoline);

- The Di Bella Method (A Fixed Part - Cyclophosphamide 50mg tablets and/or Hydroxyurea 500mg tablets, one or two per day);

- The Di Bella Method (A Fixed Part - Somatostatin, Octreotide, Sandostatin LAR, analogues and/or derivatives);

- Somatostatin in oncology, the overlooked evidences - In vitro, review and in vivo publications;

- Publication, 2018 Jul: Over-Expression of GH/GHR in Breast Cancer and Oncosuppressor Role of Somatostatin as a Physiological Inhibitor (from Di Bella's Foundation);

- Publication, 2018 Sep: The over-expression of GH/GHR in tumour tissues with respect to healthy ones confirms its oncogenic role and the consequent oncosuppressor role of its physiological inhibitor, somatostatin: a review of the literature (from Di Bella's Foundation);

- Publication, 2019 Aug: The Entrapment of Somatostatin in a Lipid Formulation: Retarded Release and Free Radical Reactivity (from Di Bella's Foundation);

- Publication, 2019 Sep: Effects of Somatostatin and Vitamin C on the Fatty Acid Profile of Breast Cancer Cell Membranes (from Di Bella's Foundation);

- Publication, 2019 Sep: Effects of somatostatin, curcumin, and quercetin on the fatty acid profile of breast cancer cell membranes (from Di Bella's Foundation);

- Publication, 2020 Sep: Two neuroendocrine G protein-coupled receptor molecules, somatostatin and melatonin: Physiology of signal transduction and therapeutic perspectives (from Di Bella's Foundation);

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