Elevated erbB‐2 oncoprotein levels in preoperative and follow‐up serum samples define an aggressive disease course in patients with breast cancer

Background. Recent evidence indicates that a soluble fragment of the erbB-2 oncogene product may be released from cell surface and become detectable in the serum of patients with breast cancer. Methods. To study the diagnostic utility of this phenomenon, the authors measured serum erbB-2 levels with a quantitative enzyme-linked immunosorbent assay in 227 preoperative samples from women who underwent breast surgery and in 339 samples from 225 patients with breast cancer during follow-up. Results. Eleven (9%) of 114 preoperative samples from patients with a histologically verified breast cancer and 2 of 113 (1.8%) from patients with benign breast tumors had elevated (greater than 20 U/ml) serum erbB-2 antigen levels. Ten (91%) of the 11 carcinomas and one of the benign tumors from patients with elevated serum erbB-2 levels also showed overexpression of the erbB-2 protein in immunohistochemical analysis of tissue sections. Elevated preoperative serum erbB-2 levels were predominantly found in patients with large tumors, and those with axillary lymph node or distant metastases. Sixty-three of the 339 (19%) follow-up samples had elevated serum erbB-2 antigen levels. Approximately one-third (30.9%) of the samples taken during recurrent disease were serum erbB-2 positive, which is close to the overall overexpression rate of this oncogene. Elevated erbB-2 levels were more common in patients whose disease was not responsive to treatment. Patients with distant metastases had elevate erbB-2 levels more often (40%) than did those with locoregional recurrence (20%). Elevated erbB-2 levels predicted the appearance of metastases within the next 6 months in 10 of 27 (37%) patients. Conclusion. The study's results suggest that assay serum erbB-2 levels may be valuable in the follow-up and monitoring of patients with breast cancer whose primary tumors show erbB-2 overexpression by immunohistochemistry.