Abstract

Abstract Introduction: Cyclooxygenase-2 (COX-2) is a mediator of inflammation and regulates aromatase expression, suggesting a potentially important role in breast cancer. The prognostic role of COX-2 expression in breast cancer is still debated. The aim of this study was to analyze tumor COX-2 expression in relation to age and tumor characteristics, and to elucidate whether COX-2 expression was associated with breast cancer prognosis. Materials and methods: COX-2 expression was evaluated in invasive tumors from 984 primary breast cancer patients from a population-based prospective cohort from Lund, Sweden. The patients were included as of 2002 and were followed for up to 11 years. The median follow-up time for patients still at risk was five years. Disease-free survival was assessed by Kaplan-Meier and LogRank test. Adjusted Hazard Ratios (HR) were obtained by Cox regression and adjusted for invasive tumor size, axillary lymph node involvement, histological grade, estrogen receptor (ER) status, and age at inclusion. Results: Immunohistochemical COX-2 expression was available for 911 patients and the intensity was classified as negative (n = 82; 9.0%) /weak or moderate (n = 723; 79.4%) /strong (n = 106; 11.6%). Patients 50 years or older at inclusion had higher COX-2 expression compared to younger patients (Ptrend = 0.05). Overall, higher COX-2 tumor expression was also observed among patients with ER+ tumors (Ptrend<0.0001) and among patients with tumors of lower histological grade (Ptrend<0.0001) compared to patients with ER- tumors or higher histological grade. COX-2 tumor expression was not associated with tumor size or axillary lymph node status. Higher COX-2 expression was associated with lower risk for any breast cancer event in the univariable (LogRank Ptrend = 0.02), but not in the multivariable model, adjusted HR 0.73 (95% CI: 0.49-1.09) per category. However, higher COX-2 expression was associated with lower risk for events during the first five years of follow-up (LogRank Ptrend = 0.0003), adjusted HR 0.60 (95% CI: 0.37-0.97) per category. Conclusion: Higher COX-2 expression was associated with less aggressive tumor characteristics and lower risk for any breast cancer event during the first five years of follow-up but not thereafter, in this population-based cohort of breast cancer patients. This study indicates that COX-2 expression in breast cancer may carry short-term prognostic information independently of established clinical and tumor characteristics. Citation Format: Maria Simonsson, Sofie Björner, Andrea Markkula, Björn Nodin, Karin Jirström, Carsten Rose, Signe Borgquist, Christian Ingvar, Helena Jernström. Tumor COX-2 expression is associated with less aggressive tumors and better five-year prognosis in breast cancer patients. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3931.

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