COX2 expression in prognosis and in prediction to endocrine therapy in early breast cancer patients

• Published in: Breast cancer research and treatment Vol. 125; no. 3; pp. 671 - 685
• Main Authors: van Nes, Johanna G. H, de Kruijf, Esther M, Faratian, Dana, van de Velde, Cornelis J. H, Putter, Hein, Falconer, Claire, Smit, Vincent T. H. B. M, Kay, Charlene, van de Vijver, Marc J, Kuppen, Peter J. K, Bartlett, John M. S
• Format: Journal Article
• Language: English
• Published: Boston Boston : Springer US 01-02-2011; Springer US; Springer; Springer Nature B.V; Springer Verlag
• Subjects: Adult; Aged; Aged, 80 and over; Analysis; Biological and medical sciences; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - enzymology; Cancer; Cancer patients; Cancer research; Cancer therapies; Care and treatment; COX2; Cyclooxygenase 2 - biosynthesis; Early breast cancer; Endocrine System; Endocrine therapy; Female; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; Gynecology. Andrology. Obstetrics; Health aspects; Humans; Immunohistochemistry; Immunohistochemistry - methods; Mammary gland diseases; Medical prognosis; Medical sciences; Medicine; Medicine & Public Health; Middle Aged; Models, Statistical; Oligonucleotide Array Sequence Analysis; Oncology; Preclinical Study; Prognosis; Prognostic and predictive factors; Tumors; Endocrine therapy; COX2; Early breast cancer; Prognostic and predictive factors; Human; Prostaglandin-endoperoxide synthase; Breast disease; Prognosis; Hormone therapy; Enzyme; Prediction; Patient; Breast cancer; Malignant tumor; Gene expression; Mammary gland diseases; Early; Oxidoreductases; Predictive factor; Cancer
• ISSN: 0167-6806; 1573-7217
• DOI: 10.1007/s10549-010-0854-7

In breast cancer, the prognostic impact of COX2 expression varies widely between studies. We examined the prognostic value of COX2 expression in a large cohort of breast cancer patients treated with primary surgery between 1985 and 1994 and explained the variable results of COX2 expression found in the literature. A tissue microarray was constructed of available tumour material, and ER, PgR, HER2, Ki67 and COX2 were examined by immunohistochemistry. Median follow-up was 19 years. Fifty-five percent (n = 369/677) of patients received no systemic treatment. COX2 was scored using a weighted histoscore. Analysis of COX2 expression in two groups based on the median (148; below vs. above) showed an increased hazard ratio (HR) of 1.35 (95% CI 1.05-1.75, P = 0.021) for disease-free survival (DFS) and of 1.39 (95% CI 1.03-1.82, P = 0.016) for overall survival (OS). However, COX2 did not remain independent in multivariate analysis. In patients with hormone receptor positive tumours, COX2 expression had a negative influence on outcome (low vs. high: DFS: HR 1.37, 95% CI 1.07-1.76, P = 0.013). This effect disappeared when endocrine therapy was administered (low vs. high: DFS: HR 0.93, 95% CI 0.51-1.70, P = 0.811) while it remained statistically significant when endocrine therapy was omitted (low vs. high: DFS: HR 1.48, 95% CI 1.12-1.94, P = 0.005). Our results show that COX2 plays a role in hormonal pathways. Our results can explain the results found in previously published studies.