Faculty Collaboration Database

Signal transducer and activator of transcription-5 activation and breast cancer prognosis. J Clin Oncol 2004 Jun 01;22(11):2053-60

Date

06/01/2004

Pubmed ID

15169792

DOI

10.1200/JCO.2004.11.046

Scopus ID

2-s2.0-2942672845 (requires institutional sign-in at Scopus site)   197 Citations

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.

Author List

Nevalainen MT, Xie J, Torhorst J, Bubendorf L, Haas P, Kononen J, Sauter G, Rui H

MESH terms used to index this publication - Major topics in bold

Adult
Aged
Aged, 80 and over
Biomarkers, Tumor
Breast Neoplasms
DNA-Binding Proteins
Disease-Free Survival
Female
Humans
Immunohistochemistry
Middle Aged
Milk Proteins
Multivariate Analysis
Predictive Value of Tests
Prognosis
STAT5 Transcription Factor
Survival Rate
Trans-Activators
Tumor Suppressor Proteins