Simonsson Maria, Björner Sofie, Markkula Andrea, Nodin Björn, Jirström Karin, Rose Carsten, Borgquist Signe, Ingvar Christian, Jernström Helena
Faculty of Medicine, Department of Clinical Sciences Lund, Oncology and Pathology, Lund University, Lund, Sweden.
CREATE Health and Department of Immunotechnology, Lund University, Medicon Village, Lund, Sweden.
Int J Cancer. 2017 Jan 1;140(1):163-175. doi: 10.1002/ijc.30432. Epub 2016 Sep 28.
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, 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 = 0.048), preoperative NSAID use (P = 0.009), and tumor size (P = 0.039). COX-2 negativity was associated with increased risk for events during the first five years in ever OC users, HR 1.94 (1.01-3.72) and during the 11-year follow-up in preoperative NSAID users, HR 4.51 (1.18-11.44) as well as in patients with large tumors, 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.
肿瘤环氧化酶2（COX-2）表达与乳腺癌预后之间的关联一直存在争议。本研究的目的是根据辅助治疗评估COX-2肿瘤表达的预后意义，以及非甾体抗炎药（NSAID）使用、其他肿瘤和生活方式因素的潜在效应修饰。对瑞典隆德2002年至2012年的1116例原发性乳腺癌患者进行前瞻性队列研究，随访至2014年6月（中位时间5年）。使用免疫组织化学在组织微阵列上评估肿瘤特异性COX-2表达。分析COX-2强度（阴性、弱阳性、强阳性）与患者和肿瘤特征以及预后之间的关联。911例患者有肿瘤特异性COX-2表达，其与诊断时年龄较大和肿瘤侵袭性较低显著相关。较高的COX-2表达与随访前五年乳腺癌事件风险较低相关，每类别风险比（HR）为0.60（95%置信区间：0.37-0.97）。COX-2表达与预后之间的关联因口服避孕药（OC）使用（P = 0.048）、术前NSAID使用（P = 0.009）和肿瘤大小（P = 0.039）而有显著修饰。在曾经使用OC的患者中，COX-2阴性与前五年事件风险增加相关，HR为1.94（1.01-3.72）；在术前使用NSAID的患者中，COX-2阴性与11年随访期间事件风险增加相关，HR为4.51（1.18-11.44）；在肿瘤较大的患者中，COX-2阴性与事件风险增加相关，HR为2.57（1.28-5.15）。总之，本研究是评估乳腺癌中COX-2表达的最大规模研究之一，表明COX-2表达的预后影响取决于宿主因素和肿瘤特征。
