PROGNOSTIC AND PREDICTIVE VALUE OF C-ERBB-2 OVEREXPRESSION IN PRIMARYBREAST-CANCER, ALONE AND IN COMBINATION WITH OTHER PROGNOSTIC MARKERS

Purpose: To investigate the prognostic and predictive value of c-erbB- 2 overexpression in breast cancer in relation to other prognostic mark ers. Patients and Methods: Paraffin-embedded tumors from consecutive p rimary breast cancer patients were screened for c-erbB-2 protein (p185 ) overexpression by immunohistochemistry using the monoclonal antibody CB11. Results: c-erbB-2 protein overexpression was defected in 19% of tumors and was associated with shorter 5-year overall survival (GAS) rate compared with c-erbB-2-negative cases in the total patient materi al (58% and 77%, respectively; P = .004) and in the 96 node-positive p atients (31% and 61%, respectively; P = .02), but not in node-negative patients. For 47 node-positive patients treated with adjuvant tamoxif en and radiotherapy, the 5-year OAS was 13% for c-erbB-2 overexpressio n and 75% for c-erbB-2-negative patients (P = .00004). The frequency o f c-erbB-2 overexpression decreased with age at diagnosis. The prognos tic value of c-erbB-2 on GAS was independent of age, node status, tumo r size, histopathologic grade, hormone receptor status, S phase, p53 s tatus, and adjuvant treatment. c-erbB-2 status added prognostic inform ation to p53-negative and low S-phase cases, but not to p53-positive a nd high S-phase cases. Correspondingly, these only added information t o c-erbB-2-negative cases. Conclusion: c-erbB-2 protein overexpression may have a predictive value with regard to adjuvant therapy in node-p ositive patients, for whom adjuvant tamoxifen with radiotherapy appear s insufficient in the presence of c-erbB-2 overexpression. Combination of con ventional and newer tumor markers may identify patients with a worse prognosis within groups with a generally favorable prognosis. ( C) 1998 by American Society of Clinical Oncology.