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Prognostic Significance of c-erbB-2 and Estrogen Receptor Status in Human Breast Cancer¹

Departments of Medical Oncology [A. H. M., D. N. C.], Pathology [P. A. D., B. M. J. T.], and Epidemiology [M. B. C.], Mater Misericordiae Hospital, Eccles Street, Dublin 7, and University College, and Department of Statistics, Trinity College [M. O'R.], Dublin, Ireland; and Imperial Cancer Research Fund, Oncology Group, Hammersmith Hospital, Du Cane Road, London, W12 OHS, England [W. J. G.]

Using the 21N polyclonal antibody, we immunohistochemically stained 314 primary breast carcinomas to identify those tumors overexpressing the c-erbB-2 oncoprotein and to ascertain the prognostic significance of this expression on disease-free and overall survival. Positive membrane staining was present in 52 (17%) of these carcinomas of which 7 (13%) were ductal carcinomas in situ. There was no significant relationship between c-erbB-2 positivity and (a) age at diagnosis, (b) menopausal status, (c) tumor size, (d) lymph node status, (e) estrogen receptor status, or (f) whether or not the patient had disseminated disease outside the axillary fields. However, c-erbB-2-positive tumors were significantly associated with poorer grade (P = 0.02). Patients who were positive for this oncoprotein had a shorter disease-free survival (P = 0.002) and reduced overall survival (P = 0.0001). Overexpression of this oncoprotein was predictive of a worse prognosis in lymph node-positive disease (P = 0.003) and in patients presenting with grade II tumors (P = 0.001). Stratifying the patients on the basis of estrogen receptor status suggested that c-erbB-2+/estrogen receptor-negative status was predictive of a poorer prognosis when compared with the other subgroups (P < 0.001). Primary and recurrent tumor tissues were available from 42 of the 314 patients. Identical patterns of c-erbB-2 expression occurred in 95% of cases, arguing against a direct role for c-erbB-2 expression in the process of tumor dissemination. The high incidence of staining in ductal carcinomas in situ suggests that expression of this oncoprotein is an early event in tumorigenesis. Finally, multivariate analysis indicated that the c-erbB-2 oncoprotein was an independent prognostic indicator for overall survival in breast carcinoma patients.

¹ This work was partially supported by the Health Research Board, Ireland.

² To whom requests for reprints should be addressed.

Received 2/16/90. Accepted 4/ 8/91.

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