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Loss of nuclear localized and tyrosine phosphorylated Stat5 in breast cancer predicts poor clinical outcome and increased risk of antiestrogen therapy failure.

Publication ,  Journal Article
Peck, AR; Witkiewicz, AK; Liu, C; Stringer, GA; Klimowicz, AC; Pequignot, E; Freydin, B; Tran, TH; Yang, N; Rosenberg, AL; Hooke, JA; Rimm, DL ...
Published in: J Clin Oncol
June 20, 2011

PURPOSE: To investigate nuclear localized and tyrosine phosphorylated Stat5 (Nuc-pYStat5) as a marker of prognosis in node-negative breast cancer and as a predictor of response to antiestrogen therapy. PATIENTS AND METHODS: Levels of Nuc-pYStat5 were analyzed in five archival cohorts of breast cancer by traditional diaminobenzidine-chromogen immunostaining and pathologist scoring of whole tissue sections or by immunofluorescence and automated quantitative analysis (AQUA) of tissue microarrays. RESULTS: Nuc-pYStat5 was an independent prognostic marker as measured by cancer-specific survival (CSS) in patients with node-negative breast cancer who did not receive systemic adjuvant therapy, when adjusted for common pathology parameters in multivariate analyses both by standard chromogen detection with pathologist scoring of whole tissue sections (cohort I; n = 233) and quantitative immunofluorescence of a tissue microarray (cohort II; n = 291). Two distinct monoclonal antibodies gave concordant results. A progression array (cohort III; n = 180) revealed frequent loss of Nuc-pYStat5 in invasive carcinoma compared to normal breast epithelia or ductal carcinoma in situ, and general loss of Nuc-pYStat5 in lymph node metastases. In cohort IV (n = 221), loss of Nuc-pYStat5 was associated with increased risk of antiestrogen therapy failure as measured by univariate CSS and time to recurrence (TTR). More sensitive AQUA quantification of Nuc-pYStat5 in antiestrogen-treated patients (cohort V; n = 97) identified by multivariate analysis patients with low Nuc-pYStat5 at elevated risk for therapy failure (CSS hazard ratio [HR], 21.55; 95% CI, 5.61 to 82.77; P < .001; TTR HR, 7.30; 95% CI, 2.34 to 22.78; P = .001). CONCLUSION Nuc-pYStat5 is an independent prognostic marker in node-negative breast cancer. If confirmed in prospective studies, Nuc-pYStat5 may become a useful predictive marker of response to adjuvant hormone therapy.

Duke Scholars

Published In

J Clin Oncol

DOI

EISSN

1527-7755

Publication Date

June 20, 2011

Volume

29

Issue

18

Start / End Page

2448 / 2458

Location

United States

Related Subject Headings

  • Young Adult
  • Tumor Suppressor Proteins
  • Treatment Failure
  • Survival Analysis
  • STAT5 Transcription Factor
  • Protein Processing, Post-Translational
  • Prognosis
  • Phosphotyrosine
  • Phosphorylation
  • Oncology & Carcinogenesis
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Peck, A. R., Witkiewicz, A. K., Liu, C., Stringer, G. A., Klimowicz, A. C., Pequignot, E., … Rui, H. (2011). Loss of nuclear localized and tyrosine phosphorylated Stat5 in breast cancer predicts poor clinical outcome and increased risk of antiestrogen therapy failure. J Clin Oncol, 29(18), 2448–2458. https://doi.org/10.1200/JCO.2010.30.3552
Peck, Amy R., Agnieszka K. Witkiewicz, Chengbao Liu, Ginger A. Stringer, Alexander C. Klimowicz, Edward Pequignot, Boris Freydin, et al. “Loss of nuclear localized and tyrosine phosphorylated Stat5 in breast cancer predicts poor clinical outcome and increased risk of antiestrogen therapy failure.J Clin Oncol 29, no. 18 (June 20, 2011): 2448–58. https://doi.org/10.1200/JCO.2010.30.3552.
Peck AR, Witkiewicz AK, Liu C, Stringer GA, Klimowicz AC, Pequignot E, et al. Loss of nuclear localized and tyrosine phosphorylated Stat5 in breast cancer predicts poor clinical outcome and increased risk of antiestrogen therapy failure. J Clin Oncol. 2011 Jun 20;29(18):2448–58.
Peck, Amy R., et al. “Loss of nuclear localized and tyrosine phosphorylated Stat5 in breast cancer predicts poor clinical outcome and increased risk of antiestrogen therapy failure.J Clin Oncol, vol. 29, no. 18, June 2011, pp. 2448–58. Pubmed, doi:10.1200/JCO.2010.30.3552.
Peck AR, Witkiewicz AK, Liu C, Stringer GA, Klimowicz AC, Pequignot E, Freydin B, Tran TH, Yang N, Rosenberg AL, Hooke JA, Kovatich AJ, Nevalainen MT, Shriver CD, Hyslop T, Sauter G, Rimm DL, Magliocco AM, Rui H. Loss of nuclear localized and tyrosine phosphorylated Stat5 in breast cancer predicts poor clinical outcome and increased risk of antiestrogen therapy failure. J Clin Oncol. 2011 Jun 20;29(18):2448–2458.

Published In

J Clin Oncol

DOI

EISSN

1527-7755

Publication Date

June 20, 2011

Volume

29

Issue

18

Start / End Page

2448 / 2458

Location

United States

Related Subject Headings

  • Young Adult
  • Tumor Suppressor Proteins
  • Treatment Failure
  • Survival Analysis
  • STAT5 Transcription Factor
  • Protein Processing, Post-Translational
  • Prognosis
  • Phosphotyrosine
  • Phosphorylation
  • Oncology & Carcinogenesis