Objective::Serum tumor markers are seldom considered as diagnostic biomarkers for breast cancer because they lack good sensitivity or specificity. This study aimed to evaluate whether a combination of circulating tumor cells (CTCs) and the serum tumor markers carcinoembryonic antigen (CEA), cancer antigen (CA)125, and CA15-3 might improve their diagnostic performance.Methods::We performed a retrospective case-control study of patients with breast cancer or benign breast diseases (BBD) and healthy female donors (HDs) who underwent preoperative CTC detection and serum tumor marker tests between December 2017 and November 2018. CTC detection and serum tumor marker test results were collected from 177 breast cancer patients, 64 patients with BBD, and 20 HDs. Correlations between CTC, CEA, CA125, or CA15-3 and participants’ clinical characteristics were then analyzed. The diagnostic performances of CTC, CEA, CA125, and CA15-3 were estimated using the area under the receiver operating characteristic curve (AUC). This study was approved by the Institutional Review Board of Sun Yat-sen Memorial Hospital of Sun Yat-sen University, China (approval No. [2018] kuaishendi(75)) on May 24, 2018.Results::CTC, CEA, and CA15-3 were able to distinguish breast cancer patients from controls (BBD+HDs) (n P<0.0001,n P=0.0006, and n P=0.0086, respectively). CTCs were associated with tumor size (n P=0.0275) and lymph node involvement (n P=0.0373), while CA15-3 was correlated with cancer stage (n P=0.01) and lymph node involvement (n P=0.001). The AUCs of CTCs, CEA, CA125, and CA15-3 were 0.845, 0.623, 0.477, and 0.58, respectively. CA125, with AUC<0.5, was not considered a biomarker for breast cancer. CEA and CA15-3 had low sensitivities (98%). Combination with CTC improved the diagnostic performances of CEA and CA15-3 for breast cancer. CTC_CA15-3 had better diagnostic performance than CTC_CEA, with an AUC of 0.874, a sensitivity of 0.757, and a specificity of 0.905.n Conclusion::CTCs, CEA, and CA15-3 are potential diagnostic biomarkers for breast cancer. The diagnostic performance of CEA and CA15-3 may be improved by combination with CTCs.“,”Objective::Serum tumor markers are seldom considered as diagnostic biomarkers for breast cancer because they lack good sensitivity or specificity. This study aimed to evaluate whether a combination of circulating tumor cells (CTCs) and the serum tumor markers carcinoembryonic antigen (CEA), cancer antigen (CA)125, and CA15-3 might improve their diagnostic performance.Methods::We performed a retrospective case-control study of patients with breast cancer or benign breast diseases (BBD) and healthy female donors (HDs) who underwent preoperative CTC detection and serum tumor marker tests between December 2017 and November 2018. CTC detection and serum tumor marker test results were collected from 177 breast cancer patients, 64 patients with BBD, and 20 HDs. Correlations between CTC, CEA, CA125, or CA15-3 and participants’ clinical characteristics were then analyzed. The diagnostic performances of CTC, CEA, CA125, and CA15-3 were estimated using the area under the receiver operating characteristic curve (AUC). This study was approved by the Institutional Review Board of Sun Yat-sen Memorial Hospital of Sun Yat-sen University, China (approval No. [2018] kuaishendi(75)) on May 24, 2018.Results::CTC, CEA, and CA15-3 were able to distinguish breast cancer patients from controls (BBD+HDs) (n P<0.0001,n P=0.0006, and n P=0.0086, respectively). CTCs were associated with tumor size (n P=0.0275) and lymph node involvement (n P=0.0373), while CA15-3 was correlated with cancer stage (n P=0.01) and lymph node involvement (n P=0.001). The AUCs of CTCs, CEA, CA125, and CA15-3 were 0.845, 0.623, 0.477, and 0.58, respectively. CA125, with AUC<0.5, was not considered a biomarker for breast cancer. CEA and CA15-3 had low sensitivities (98%). Combination with CTC improved the diagnostic performances of CEA and CA15-3 for breast cancer. CTC_CA15-3 had better diagnostic performance than CTC_CEA, with an AUC of 0.874, a sensitivity of 0.757, and a specificity of 0.905.n Conclusion::CTCs, CEA, and CA15-3 are potential diagnostic biomarkers for breast cancer. The diagnostic performance of CEA and CA15-3 may be improved by combination with CTCs.