C-erbB-2 oncogene protein (ErbB-2/HER-2) overexpression is a prognostic marker of breast carcinoma. The purpose of this study was to evaluate serum ErbB-2 for monitoring tumor recurrence of operable breast carcinoma patients. The subjects were 86 breast carcinoma patients with stage I-IIIB. Sera were collected at preoperative and postoperative periods from 1996 to 2000. The cutoff value was set at 5.4 ng/ml for preoperative patients and at 6.5 ng/ ml for postoperative patients. Twenty-nine patients (34%) had higher preoperative serum ErbB-2 levels ( 5.4 ng/ml). A higher preoperative serum ErbB-2 was associated with higher clinical stage, larger tumor size, nodal metastasis, higher histologic grade and lymphatic invasion, but not with vascular invasion, hormonal receptor status or other tumor markers, such as carcinoembryonic antigen (CEA) and carbohydrate antigen 15-3 (CA15-3). As of April 2005, 27 patients (31%) had recurrence and 18 (62%) of them had a higher preoperative serum ErbB-2. Seventeen patients died of tumor progression. The recurrence-free survival rates at 7 years after breast surgery were 84% in 57 patients with a normal preoperative serum ErbB-2 and 41% in 29 patients with a higher preoperative serum ErbB-2 (p < 0.0001). The overall survival rates at 7 years were 93% and 55% (p < 0.0001), respectively. A multivariate analysis revealed that preoperative serum ErbB-2 was an independent prognostic factor for recurrence-free survival and overall survival in breast carcinoma patients. The specificities and sensitivities of postoperative tumor markers (CEA, CA15-3 and ErbB-2) were 91%, 100% and 85%, and 40%, 30% and 70%, respectively. Serum ErbB-2 is a preoperative prognostic marker and may be useful for monitoring tumor recurrence of the breast. ' 2006 Wiley-Liss, Inc.Key words: breast carcinoma; serum ErbB-2; tumor marker; prognosis Slamon et al. first reported that overexpression of the c-erbB-2 proto-oncogene was associated with a poor prognosis of primary breast carcinoma. 1 The c-erbB-2 protein (ErbB-2/HER-2) is a transmembrane protein of 185 kD, and the extracellular domain had been detected in conditioned medium from human breast carcinoma cell lines and in sera from recurrent breast carcinoma patients. 2 Narita et al. first measured serum ErbB-2 in patients with benign breast disease, primary breast carcinoma and recurrent breast carcinoma. 3 Isola et al. suggested the utility of serum ErbB-2 for monitoring the tumor progression of patients with ErbB-2-positive breast carcinoma. 4 Kandl et al. reported the correlation between elevated serum ErbB-2 and poor prognosis of advanced breast carcinoma. 5 On the other hand, Willsher et al. showed the prognostic importance of serum ErbB-2 in early breast carcinoma patients. 6 In addition, Molina et al. demonstrated that abnormally presurgical serum ErbB-2 was related to the poor prognosis of node-positive and node-negative breast carcinoma. 7 Taken together, serum ErbB-2 is associated with tumor progression or tumor recurrence of the breast. However, ...