Cyclo-oxygenase-2 expression is associated with poor clinical outcome after doxorubicin-based chemotherapy in node-positive breast cancer: integration of tissue microarray

Introduction

We performed this study to evaluate the frequency and clinical implications of cyclo-oxygenase (COX)-2 expression in clinical breast cancer.

Method

COX-2 expression was analyzed on tissue microarray (TMA) of 178 node-positive patients treated with doxorubicin-based adjuvant chemotherapy by immunohistochemistry (IHC).

Results

COX-2 was over-expressed in 70 (39.3%) out of 178 invasive breast cancers. COX-2 expression was significantly increased in undifferentiated tumor with high S-phase fraction. COX-2 expression appeared to be increased in HER2-amplified tumors but the difference was not statistically significant. There was no significant association between COX-2 over-expression and other clinical and biologic profiles such as tumor size, histologic grade, and oestrogen receptor (ER) expression. Disease-free survival (DFS) and overall survival (OS) of the patients with COX-2 expressing tumor was significantly decreased compared with the patients with COX-2 negative tumor (P = 0.009 for DFS, P = 0.011 for OS). COX-2 expression and histologic grade were significant prognostic factors for DFS and OS in multivariate analysis.

Conclusion

The intimate association of COX-2 expression with increased S-phase and high histologic grade, together with poor clinical outcomes for COX-2 expressing tumors, indicates that COX-2 expression represents a highly aggressive phenotype of breast cancer.