Document Detail

Low levels of Stat5a protein in breast cancer are associated with tumor progression and unfavorable clinical outcomes.
MedLine Citation:
PMID:  23036105     Owner:  NLM     Status:  Publisher    
ABSTRACT: INTRODUCTION: Signal transducer and activator of transcripton-5a (Stat5a) and its close homolog, Stat5b, mediate key physiological effects of prolactin and growth hormone in mammary glands. In breast cancer, loss of nuclear localized and tyrosine phosphorylated Stat5a/b is associated with poor prognosis and increased risk of antiestrogen therapy failure. Here we quantify for the first time levels of Stat5a and Stat5b over breast cancer progression, and explore their potential association with clinical outcome. METHODS: Stat5a and Stat5b protein levels were quantified in situ in a breast cancer progression material. Stat5a and Stat5b transcript levels in breast cancer were correlated with clinical outcome in 936 patients. Stat5a protein was further quantified in four archival cohorts totaling 686 patients with clinical outcome data using multivariate models. RESULTS: Protein levels of Stat5a but not Stat5b were reduced in primary breast cancer and lymph node metastases compared to normal epithelia. Low tumor levels of Stat5a but not Stat5b mRNA were associated with poor prognosis. Experimentally, only limited overlap between Stat5a and Stat5b-modulated genes was found. In two cohorts of therapy-naive, node-negative breast cancer patients, low nuclear Stat5a protein levels were an independent marker of poor prognosis. Multivariate analysis of two cohorts treated with antiestrogen monotherapy revealed that low nuclear Stat5a levels were associated with more than 4-fold risk of unfavorable outcome. CONCLUSIONS: Loss of Stat5a represents a new independent marker of poor prognosis in node-negative breast cancer, and may be a predictor of response to antiestrogen therapy if validated in randomized clinical trials.
Amy R Peck; Agnes K Witkiewicz; Chengbao Liu; Alexander C Klimowicz; Ginger A Stringer; Edward Pequignot; Boris Freydin; Ning Yang; Adam Ertel; Thai H Tran; Melanie A Girondo; Anne L Rosenberg; Jeffrey A Hooke; Albert J Kovatich; Craig D Shriver; David L Rimm; Anthony M Magliocco; Terry Hyslop; Hallgeir Rui
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-10-4
Journal Detail:
Title:  Breast cancer research : BCR     Volume:  14     ISSN:  1465-542X     ISO Abbreviation:  Breast Cancer Res.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-5     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100927353     Medline TA:  Breast Cancer Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  R130     Citation Subset:  -    
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