title: COX2 expression in prognosis and in prediction to endocrine therapy in early breast cancer patients.
abstract: 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.
authors.affiliation: Department of Surgery, Leiden University Medical Centre, Leiden, The Netherlands.
authors.forename: Johanna G H
authors.initials: JG
authors.lastname: van Nes
authors.forename: Esther M
authors.initials: EM
authors.lastname: de Kruijf
authors.forename: Dana
authors.initials: D
authors.lastname: Faratian
authors.forename: Cornelis J H
authors.initials: CJ
authors.lastname: van de Velde
authors.forename: Hein
authors.initials: H
authors.lastname: Putter
authors.forename: Claire
authors.initials: C
authors.lastname: Falconer
authors.forename: Vincent T H B M
authors.initials: VT
authors.lastname: Smit
authors.forename: Charlene
authors.initials: C
authors.lastname: Kay
authors.forename: Marc J
authors.initials: MJ
authors.lastname: van de Vijver
authors.forename: Peter J K
authors.initials: PJ
authors.lastname: Kuppen
authors.forename: John M S
authors.initials: JM
authors.lastname: Bartlett
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology*; D051546:Cyclooxygenase 2 / Q000096:biosynthesis*; D004703:Endocrine System; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008875:Middle Aged; D015233:Models, Statistical; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis
chemical_list: D051546:Cyclooxygenase 2