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 e rbB-2 oncogene product may be released from cell surface and become de tectable in the serum of patients with breast cancer. Methods. To stud y the diagnostic utility of this phenomenon, the authors measured seru m erbB-2 levels with a quantitative enzyme-linked immunosorbent assay in 227 preoperative samples from women who underwent breast surgery an d 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 patie nts with benign breast tumors had elevated (greater than 20 U/ml) seru m erbB-2 antigen levels. Ten (98%) of the 11 carcinomas and one of the benign tumors from patients with elevated serum erbB-2 levels also sh owed overexpression of the erbB-2 protein in immunohistochemical analy sis of tissue sections. Elevated preoperative serum erbB-2 levels were predominantly found in patients with large tumors, and those with axi llary lymph node or distant metastases. Sixty-three of the 339 (19%) f ollow-up samples had elevated serum erbB-2 antigen levels. Approximate ly one-third (30.9%) of the samples taken during recurrent disease wer e serum erbB-2 positive, which is close to the overall overexpression rate of this oncogene. Elevated erbB-2 levels were more common in pati ents whose disease was not responsive to treatment. Patients with dist ant metastases had elevate erbB-2 levels more often (40%) than did tho se with locoregional recurrence (20%). Elevated erbB-2 levels predicte d the appearance of metastases within the next 6 months in 10 of 27 (3 7%) patients. Conclusion. The study's results suggest that assay serum erbB-2 levels may be valuable in the follow-up and monitoring of pati ents with breast cancer whose primary tumors show erbB-2 overexpressio n by immunohistochemistry.