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.