Elevated expression of cyclooxygenase-2 is a negative prognostic factor for disease free survival and overall survival in patients with breast carcinoma

Carsten Denkert, Klaus Jürgen Winzer, Berit Maria Müller, Wilko Weichert, Sören Pest, Martin Köbel, Glen Kristiansen, Angela Reles, Antje Siegert, Hans Guski, Steffen Hauptmann

Research output: Contribution to journalArticlepeer-review

221 Scopus citations

Abstract

BACKGROUND. Cyclooxygenases regulate the production of prostaglandins and play a role in tumor development and progression. The authors investigated the prognostic impact of expression of the cyclooxygenase (COX) isoforms, COX-1 and COX-2, on disease-free survival and progression-free survival in patients with primary breast carcinoma as well as the association between COX expression and other clinicopathologic parameters. METHODS. In this study COX isoform expression was determined by immunohistochemistry in a cohort of 221 patients with primary breast carcinoma. RESULTS. Expression of COX-2 was detected in 36% of breast carcinoma samples and was associated significantly with several clinicopathologic parameters, including positive lymph node status (P < 0.0005), larger tumor size (P < 0.0005), poor differentiation (P < 0.0005), vascular invasion (P = 0.03), and negative estrogen receptor status (P = 0.04). In contrast, COX-1 was expressed in 45% of tumors and was associated with smaller tumor size (P = 0.02) and with negative lymph node status (P = 0.01). In a univariate survival analysis, a significant association was observed between elevated COX-2 expression and decreases in disease-free survival (P = 0.0007) and overall survival (P = 0.02). In a multivariate analysis, expression of COX-2 was of borderline significance for disease-free survival (relative risk, 1.90; 95% confidence interval, 1.00-3.59), adjusting for tumor size, histologic grade, number of positive lymph nodes, and patient age. Elevated expression of COX-1 in tumor tissue had no statistically significant influence on patient prognosis. CONCLUSIONS. The current data suggest that increased expression of COX-2 may play a role in the progression of primary breast carcinoma. It remains to be investigated whether treatment with selective inhibitors of COX-2 may be an additional therapeutic option for patients with breast carcinoma.

Original languageEnglish
Pages (from-to)2978-2987
Number of pages10
JournalCancer
Volume97
Issue number12
DOIs
StatePublished - 15 Jun 2003
Externally publishedYes

Keywords

  • Breast carcinoma
  • Cyclooxygenase-1
  • Cyclooxygenase-2
  • Prognostic factor

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