Moderate HER2 expression as a prognostic factor in hormone receptor positive breast cancer

Overexpression and/or amplification of human epidermal growth factor receptor 2 (HER2) is associated with poor prognosis in breast cancer and predicts response to anti-HER2 therapy in breast cancer. The prognostic relevance of moderate expression of HER2 is unclear. Data of 9872 patients with primary nonmetastatic breast cancer from the cancer registries of Magdeburg and Halle, Germany, were analyzed retrospectively. A total of 5907 patients with complete data sets including follow-up were eligible for analysis. HER2 status was determined as recommended by international guidelines. Of 5907 patients investigated, 5023 (68.4%) had HER2 0 and 1+ expression and 884 (12.0%) had HER2 (2+)/HER2- expression. Patients with hormone receptor positive (HR+) and HER2 (2+) tumors had a shorter median disease-free survival (DFS; P<0.0001) and breast cancer specific survival (BCSS; P=0.019) than HR+ patients with HER2 (0/1+) tumors. Among patients with HR- breast cancer there was no significant difference between HER2 (2+) and HER2 (0/1+) tumors. In multivariate analysis after adjustment for other prognostic factors, HER2 (2+) status remained an unfavorable prognostic factor for DFS (hazard ratio (HR)=1.217, 95% CI=1.052-1.408; P=0.008) but not for BCSS (HR=1.045, 95% CI=0.926-1.178; P=0.474). The HER2 (2+) status is an unfavorable prognostic factor for survival of patients with HR+ breast cancer. The impact of anti-HER2 therapy in this group of patients should be evaluated.