The prognostic impact of COX-2 expression in breast cancer depends on oral contraceptive history, preoperative NSAID use, and tumor size

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• 作者：Maria Simonsson ; Sofie Bjö ; rner ; Andrea Markkula ; Bjö ; rn Nodin ; Karin Jirströ ; m ; Carsten Rose ; Signe Borgquist ; Christian Ingvar and Helena Jernströ ; m
• 刊名：International Journal of Cancer
• 出版年：2017
• 出版时间：1 January 2017
• 年：2017
• 卷：140
• 期：1
• 页码：163-175
• 全文大小：610K
• ISSN：1097-0215

文摘

The association between tumor cyclooxygenase 2 (COX-2) expression and breast cancer prognosis has been inconsistent. The purpose of this study was to evaluate the prognostic significance of COX-2 tumor expression according to adjuvant treatment, and potential effect modifications of non-steroid anti-inflammatory drug (NSAID) use, and other tumor and lifestyle factors. A prospective cohort of 1,116 patients with primary breast cancer in Lund, Sweden, included 2002-2012 was followed until June 2014 (median 5 years). Tumor-specific COX-2 expression was evaluated on tissue microarrays using immunohistochemistry. Associations between COX-2 intensity (negative, weak-moderate, high) and patient and tumor characteristics as well as prognosis were analyzed. Tumor-specific COX-2 expression was available for 911 patients and was significantly associated with higher age at diagnosis and less aggressive tumor characteristics. Higher COX-2 expression was associated with lower risk for breast cancer events during the first five years of follow-up, _adjHR 0.60 (95%CI: 0.37-0.97), per category. The association between COX-2 expression and prognosis was significantly modified by oral contraceptive (OC) use (P_interaction = 0.048), preoperative NSAID use (P_interaction = 0.009), and tumor size (P_interaction = 0.039). COX-2 negativity was associated with increased risk for events during the first five years in ever OC users, _adjHR 1.94 (1.01-3.72) and during the 11-year follow-up in preoperative NSAID users, _adjHR 4.51 (1.18-11.44) as well as in patients with large tumors, _adjHR 2.57 (1.28-5.15). In conclusion, this study, one of the largest evaluating COX-2 expression in breast cancer, indicates that the prognostic impact of COX-2 expression depends on host factors and tumor characteristics.