QS111. Correlation of COX-2 Expression With Triple Receptor Negative Status in Operable Human Breast Cancer

Abstract

Objective: COX-2 expression has been associated with large tumor size, high histological grade, negative hormone receptor status, high proliferation rate, axillary node metastases and ductal type of histology. We hypothesized that increased COX-2 expression is associated with triple receptor-negative status (negative for the activation of ER and PgR, and for the expression/amplification of HER2) in primary breast tumors as these tumors are aggressive and have a worse prognosis. Methods: Clinical and pathological data were collected from 109 patients with operable breast cancer enrolled in a prospective clinical trial comparing primary tumor characteristics from tumor tissue collected at definitive surgery for primary breast cancer (Stage I-III) with micrometastatic disease in bilateral bone marrow aspirates and peripheral blood. Primary tumors were immunostained with a monoclonal antibody directed against COX-2. Positive status was determined as 5% or more of tumor cells staining positive. The CellSearch system (Veridex Corporation, Warren NJ) was used to detect CTCs in whole peripheral blood. CTCs were defined as nucleated cells lacking CD45 but expressing cytokeratins 8, 18, or 19. The presence of 1 or more epithelial cells per 10 mL of blood was considered a positive result. Bone marrow aspirates were obtained from bilateral iliac crests. Anti-cytokeratin antibody was used to assess for the presence of DTCs. One or more cytokeratin positive cells were considered a positive result for DTCs. Primary tumor characteristics studied: tumor size, ER, PgR, HER2, tumor grade, histological type, lympho-vascular invasion (LVI), Ki-67 and lymph node metastasis. Statistical analysis utilized Chi squared test. Results: Currently, we have assessed 83 primary tumor specimens for COX-2 expression. Triple-negative status was present in 29% (32/109) patients and COX-2 expression was present in 29% (24/93). There was no statistically significant correlation between triple-negative receptor status and tumor size, histological type, lymph node metastasis, CTC status, and DTC status. Patients with triple receptor-negative status tended to express COX-2 more frequently than patients with any one of the receptors being positive (p =0.001, OR =5.79). Statistically significant correlations were also obtained between triple receptor-negative status and grade of tumor (p <0.001, OR =6.53) and Ki-67 (p=0.01, OR=6.43). Conclusions: Triple receptor-negative primary breast tumors express high levels of COX-2 as compared to tumors expressing any one of the three primary tumor markers. Identifying this subset of patients expressing increased COX-2 production could open a potential avenue of treating them with COX-2 inhibitors.