Abstract P6-10-01: The Association between the Use of Selective COX-2 Inhibitors and Breast Cancer Recurrence

Abstract

Abstract Introduction: There have been biological findings alluding to the role of selective COX-2 inhibitors in reducing the risk of developing cancers including breast cancer. Epidemiological data suggest that COX-2 inhibitors may prevent the development of cancers, including colorectal, esophageal and lung cancer. To date, there exists no study that reported any relationship between their use and the risk of breast cancer recurrence. Thus, we investigated the associations between the use of COX-2 inhibitors and the risk of tumor recurrence among breast cancer patients. Methods: We reviewed the medical records of female patients diagnosed with stage II/III breast cancer in Albert Einstein Medical Center between 1999 and 2005 and later reached no evident disease (NED) stage. Follow up period was from 1999 to 2008 with mean and maximum being 4.4 years and 9.8 years, respectively. COX-2 inhibitor user was defined as patients taking the medication in NED stage for at least 6 months. Age, race, family history, smoking history, menopausal status, diabetes, HER2/Neu status, hormone receptor status, TNM stage, histology, and treatment received were compared between COX-2 inhibitor users and nonusers. The primary outcome was disease free survival. The secondary outcome was overall survival. Multivariate analyses were performed using Cox proportional hazard model. Results: Of 682 cancer patients, 7.3 % (n=50) were prescribed COX-2 inhibitor; 10.0 % (5/50) of patients developed recurrence among COX-2 inhibitor users, while 22.0% (139/632) did among nonusers (chi-square test: P<0.05). COX-2 inhibitor use was negatively associated with cancer recurrence (hazard ratio [HR], 0.41; 95% confidence interval[CI], 0.17-1.00; P=0.05). Variables associated with recurrence in multivariate model were race (Caucasian vs. non-Caucasian; adjusted hazard ratio [AHR], 1.83; 95% CI, 1.20-1.84; P<0.01) and number of nodes ≥3 (AHR, 2.22; 95% CI, 1.24-3.98; P<0.01). In multivariate analysis, the association between COX-2 inhibitor use and cancer recurrence only suggestive (AHR, 0.35; 95% CI; 0.11-1.12; P=0.07). Kaplan-Meier survival analysis revealed that COX-2 inhibitor use was related to disease-free survival benefit (log-rank test P<0.05). 5 year survival was 0.88 for COX-2 inhibitor users, and 0.77 for non-users. However, COX-2 inhibitor use was not associated with reduced overall mortality in breast cancer patients (AHR, 0.49; 95% CI: 0.15-1.58; P=0.23; log-rank test P=0.12) K-M Survival Curve of Breast Cancer Recurrence Conclusions: The use of COX-2 inhibitors seems to be related to a reduced risk of developing recurrence in patients with breast cancer. This result provides the clinical evidence, in accordance with existing biological data, that COX-2 inhibitor use in breast cancer patients may be inversely associated with tumor recurrence. However, prospective randomized trials are required to validate our finding. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-10-01.