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Signal Transducer and Activator of Transcription-5 Activation and Breast Cancer Prognosis

From the Lombardi Comprehensive Cancer Center, Department of Oncology, Georgetown University; Institute for Pathology, University of Basel, Basel, Switzerland; and Diomeda Life Sciences Inc, Sun Prairie, WI.

Address reprint requests to Hallgeir Rui, Lombardi Comprehensive Cancer Center NRB E504, Georgetown University, 3970 Reservoir Rd NW, Washington, DC 20057-1469; e-mail: ruih{at}georgetown.edu

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.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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