Prognostic impact of cyclooxygenase-2 in breast cancer

Cyclooxygenase (COX)-2, an inducible isoform of cyclooxygenases, regulates the rapid production of high levels of prostaglandins during inflammation. Cyclooxygenase-2 is overexpressed in a variety of malignant tumors. This review discusses epidemiologic and preclinical data on the role of COX-2 in the development and progression of breast cancer, and it will focus on recent studies that investigate the prognostic role of COX-2 in breast cancer. In rodent tumor models it has been shown that treatment with COX-1 or COX-2 inhibitors reduces incidence and growth of breast carcinomas. Possible mechanisms include regulation of invasion, increased proliferation, and suppression of apoptosis by COX-2. Moreover, there may be an indirect effect of prostaglandins, for example in tumor host interactions such as induction of stromal aromatase activity or enhancement of angiogenesis in tumor tissue. At least 8 different immunohistochemical studies have investigated expression of COX-2 in a total of 2392 primary breast carcinomas, of which 40% were found to be COX-2 positive. Overexpression of COX-2 is associated with indicators of poor prognosis, such as lymph node metastasis, poor differentiation, and large tumor size. Four studies have found that overexpression of COX-2 is linked to poor prognosis in breast cancer. These investigations provide the basis for further evaluation of a possible therapeutic effect of COX inhibitors in therapy of breast cancer.