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

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 pat...

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Published in:Cancer 2003-06, Vol.97 (12), p.2978-2987
Main Authors: Denkert, Carsten, Winzer, Klaus‐Jürgen, Müller, Berit‐Maria, Weichert, Wilko, Pest, Sören, Köbel, Martin, Kristiansen, Glen, Reles, Angela, Siegert, Antje, Guski, Hans, Hauptmann, Steffen
Format: Article
Language:English
Subjects:
Adult
Biological and medical sciences
breast carcinoma
Breast Neoplasms - enzymology
Breast Neoplasms - mortality
Breast Neoplasms - pathology
Carcinoma - enzymology
Carcinoma - mortality
Carcinoma - pathology
Cohort Studies
Cyclooxygenase 1
Cyclooxygenase 2
Disease-Free Survival
Female
Gynecology. Andrology. Obstetrics
Humans
Isoenzymes - metabolism
Lymphatic Metastasis
Mammary gland diseases
Medical sciences
Membrane Proteins
Middle Aged
Prognosis
prognostic factor
Prostaglandin-Endoperoxide Synthases - metabolism
Survival Analysis
Tumors
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Summary: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. Cancer 2003;97:2978–87. © 2003 American Cancer Society. DOI 10.1002/cncr.11437 The authors evaluated the prognostic impact of expression of cyclooxygenase‐1 (COX‐1) and COX‐2 in a cohort of 221 patients with breast carcinoma. The most important result of the study was that COX‐2, but not COX‐1, was associated significantly with reduced disease‐free survival and overall survival.
ISSN:0008-543X
1097-0142
DOI:10.1002/cncr.11437