Prognostic value of c‐erbB2 overexpression in axillary lymph node positive breast cancer. Results from a randomized adjuvant treatment protocol

Background. This study was designed to evaluate the prognostic importance of c‐erbB2 overexpression in a standardized cohort of patients with axillary lymph node positive breast cancer. Methods. Paraffin embedded primary breast cancers from 354 patients with axillary lymph node positive breast cancer, treated on a North Central Cancer Treatment Group adjuvant protocol, were studied immunohistochemically. c‐erbB2 staining was classified as negative, weak (1+), moderate (2+), or strong (3+) and was assessed for effectiveness as a predictor of outcome in univariate and Cox model multivariate analyses. Results. Twenty percent of specimens exhibited moderate or strong c‐erbB2 staining. The median disease free survival period of the strong staining group was 2.9 years, compared with 7.1 years for all other patients (P = 0.01). The median overall survival for the strong staining group was 5 years, compared with 12 years for all other patients (P = 0.03). A definite correlation was noted between degree of nodal involvement and the likelihood of strong c‐erbB2 staining (P = 0.001). There was also a significant correlation between c‐erbB2 staining and higher nuclear grade and estrogen receptor negativity. In a multivariate analysis, c‐erbB2 staining was not a significant predictor of either disease free survival or overall survival. Conclusion. According to this analysis, the strong correlation between c‐erbB2 expression and degree of nodal involvement, higher grade disease, and estrogen receptor negativity suggests expression of this protooncogene product in a biologically more aggressive form of breast cancer. In a multivariate analysis, c‐erbB2 expression was not an independent prognostic factor. Thus, c‐erbB2 assessment did not appear to add significantly to the information provided by currently available standard disease parameters.