Prognostic importance of c-erbB-2 expression in breast cancer. International (Ludwig) Breast Cancer Study Group.

Abstract

To evaluate the prognostic importance of immunocytochemically determined c-erbB-2 overexpression in the primary tumors of patients with breast cancer. Primary tumors from 1,506 breast cancer patients (760 node-negative and 746 node-positive) who were treated in the International (Ludwig) Breast Cancer Study Group Trial V were studied. Node-negative patients were allocated randomly to either a single cycle of perioperative chemotherapy (PeCT) or no adjuvant treatment, and node-positive patients received either a prolonged chemotherapy (with tamoxifen for postmenopausal patients) or a single perioperative cycle. Tumors from 16% of the node-negative patients and 19% of the node-positive patients were found to be c-erbB-2-positive. In both groups c-erbB-2 positivity correlated with negative progesterone receptors (PR), negative estrogen receptors (ER), and high tumor grade. Lobular carcinomas were all negative, and, thus support the view that such tumors represent a defined subtype of breast carcinoma. The expression of c-erbB-2 was prognostically significant for node-positive but not for node-negative patients. However, in both subgroups, the prognostic significance was greater for patients who had received more adjuvant therapy. For node-positive patients, the effect of prolonged-duration therapy on disease-free survival (DFS) was greater for patients without c-erbB-2 overexpression (hazards ratio [HR], = 0.57; 95% confidence interval [CI], 0.46 to 0.72) than for those with c-erbB-2 overexpression (HR, 0.77; 95% CI, 0.51 to 1.16). Similarly, for node-negative patients, the effect of PeCT on DFS was greater for those without c-erbB-2 overexpression (HR, 0.82; 95% CI, 0.61 to 1.09) than for those with c-erbB-2 overexpression (HR, 1.22; 95% CI, 0.66 to 2.25). We conclude that tumors with overexpression of the c-erbB-2 oncogene are less responsive to cyclophosphamide, methotrexate, and fluorouracil (CMF)-containing adjuvant therapy regimens than those with a normal amount of gene product.