Overexpression of c-erbB2 is an independent marker of resistance to endocrine therapy in advanced breast cancer

The present study investigated the interaction between c-erbB2 overexpressi on and the response to first-line endocrine therapy in patients with advanc ed breast cancer. The primary tumours of 241 patients who were treated at f irst relapse with endocrine therapy were assessed for overexpression of c-e rbB2 by immunohistochemistry. c-erbB2 was overexpressed in 76 (32%) of prim ary breast cancers and did not correlate with any other prognostic factor. The overall response to treatment and time to progression were significantl y lower in patients with c-erbB2-positive tumours compared to those that we re c-erbB2-negative (38% vs 56%, P = 0.02; and 4.1 months vs 8.7 months, P < 0.001, respectively). In multivariate analysis, c-erbB2 status was the mo st significant predictive factor for a short time to progression (P = 0.000 9). In patients with ER-positive primary tumours treated at relapse with ta moxifen (n = 170), overexpression of c-erbB2 was associated with a signific antly shorter time to progression (5.5 months vs 11.2 months, P < 0.001). I n conclusion, overexpression of c-erbB2 in the primary tumour is an indepen dent marker of relative resistance to first-line endocrine therapy in patie nts with advanced breast cancer. In patients with ER-positive primary tumou rs, the overexpression of c-erbB2 defines a subgroup less likely to respond to endocrine therapy.