Objective This study aimed to evaluate serum and nipple discharge levels of carcinoembryonic antigen(CEA) and cancer antigen 153(CA153) and tissue cyclooxygenase-2(COX-2) expression in breast cancer cases and associations of these proteins with breast cancer metastasis.Methods The immunohistochemical Ultra Sensitive~(TM) S-P method was used to detect COX-2 expression in 77 cases of invasive breast carcinoma. Of these cases, 52 exhibited CEA and CA153 in both serum and nipple discharge(electrochemiluminescence method), and associations of these biomarkers with breast cancer prognosis were studied. Sixty cases of benign breast lesion were selected as a control group. Overall survival of breast carcinoma patients was evaluated. COX-2 expression was evaluated relative to clinicopathological features and CEA and CA153 levels, and its role in invasiveness was investigated.Results Among cases of invasive breast cancer, 72.7%(56/77) were COX-2 immunopositive, compared to 16.7% of benign lesions(χ2 = 66.745, P = 0.000) percentage of positive cells. COX-2 overexpression in breast cancer correlated positively with histological grade(II vs III; χ2 = 4.064, P = 0.043), lymph node metastasis(χ2 = 9.135, P = 0.003), and distant metastasis(χ2 = 8.021, P = 0.003). However, COX-2 expression did not correlate with age(≤ 50 vs 50 years) or tumor size(≤ 5 vs > 5 cm)(χ2 = 0.081, P = 0.776 and χ2 = 3.702, P = 0.054, respectively). Among breast cancer patients, COX-2 overexpression in tumors also correlated with shorter overall survival(P < 0.05). In brief, increased COX-2 expression correlates with worse prognosis and shorter overall survival. Malignant lesions were associated with significantly higher serum and nipple discharge levels of biomarkers, relative to benign lesions(P < 0.05). These biomarkers were present at significantly higher levels in nipple discharge than in serum(P < 0.05). Furthermore, significantly higher nipple discharge levels of CEA and CA153 were observed in COX-2-positive breast carcinoma patients, compared to COX-2-negative patients(P <0.05). Shorter overall survival in cancer patients group related to COX-2 overexpression in tumors(P < 0.05).Conclusion The study suggests that COX-2 overexpression correlates with poor clinicopathological parameters in breast cancers and might be an important biological marker of invasion and metastasis. The findings of the present study suggest that combined detection of COX-2 tissue expression and CEA and CA153 in serum and nipple discharge could facilitate clinical monitoring and diagnosis of metastasis in patients with breast cancer. Objective This study aimed at evaluating serum and nipple discharge levels of carcinoembryonic antigen (CEA) and cancer antigen 153 (CA153) and tissue cyclooxygenase-2 (COX-2) expression in breast cancer cases and associations of these proteins with breast cancer metastasis. Methods The immunohistochemical Ultra Sensitive ™ SP method was used to detect COX-2 expression in 77 cases of invasive breast carcinoma. Of these cases, 52 exhibited CEA and CA153 in both serum and nipple discharge (electrochemiluminescence method), and associations of these Sixty cases of benign breast lesion were selected as a control group. Overall survival of breast carcinoma patients was evaluated. COX-2 expression was evaluated relative to clinicopathological features and CEA and CA153 levels, and its role in Invasion was was investigated. Results of cases of invasive breast cancer, 72.7% (56/77) were COX-2 immunopositive, compared to 16.7% of benign lesion (χ2 = 66.745, P = 0.000) percentage of positive cells. COX-2 overexpression was positively correlated with histological grade in the breast cancer (χ2 = 4.064, P = 0.043) = 0.003), and distant metastasis (χ2 = 8.021, P = 0.003). However, COX-2 expression did not correlate with age (≤ 50 vs 50 years) or tumor size , P = 0.776 and χ2 = 3.702, P = 0.054, respectively). In breast cancer patients, COX-2 overexpression in tumors also correlated with shorter overall survival (P <0.05) prognosis and shorter overall survival. Malignant lesions were associated with significantly higher serum and nipple discharge levels of biomarkers, relative to benign lesions (P <0.05). These biomarkers were at significantly higher levels in nipple discharge than serum (P <0.05) Furthermore, significantly higher nipple discharge levels of CEA and CA153 were observed in COX-2-positive breast carcinoma patients, compared to COX-2-negative patients (P <0.05). Shorter overall survival in cancer patients group related to COX-2 overexpression in tumors (P <0.05) .Conclusion The study suggests that COX-2 overexpression correlates with poor clinicopathological parameters in breast cancers and might be an important biological marker of invasion and metastasis. The findings of the present study suggest that combined detection of COX-2 tissue expression and CEA and CA153 in serum and nipple discharge could facilitate clinical monitoring and diagnosis of metastasis in patients with breast cancer.