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The prognostic impact of COX‐2 expression in breast cancer depends on oral contraceptive history, preoperative NSAID use, and tumor size
Author(s) -
Simonsson Maria,
Björner Sofie,
Markkula Andrea,
Nodin Björn,
Jirström Karin,
Rose Carsten,
Borgquist Signe,
Ingvar Christian,
Jernström Helena
Publication year - 2016
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.30432
Subject(s) - medicine , breast cancer , proportional hazards model , oncology , cancer , tissue microarray , prospective cohort study , immunohistochemistry , cohort , gynecology
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, adj HR 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, adj HR 1.94 (1.01‐3.72) and during the 11‐year follow‐up in preoperative NSAID users, adj HR 4.51 (1.18‐11.44) as well as in patients with large tumors, adj HR 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.