Prognostic value of HER-2/neu overexpression for the development of brain metastasis after treatment of early breast cancer

Abstract

21044 Background: Several studies have addressed the incidence of brain metastasis in HER-2/neu-overexpressing metastatic breast cancer. However, the relevance of HER-2/neu overexpression as a risk factor for brain metastases in breast cancer has not yet been clearly defined. The aim of this study is to analyze the risk of brain metastasis in HER-2/neu-positive early breast cancer patients in comparison with HER-2/neu-negative patients. Methods: We used tissue microarray to examine HER- 2/neu overexpression by immunohistochemistry (IHC) in 773 consecutive patients diagnosed with breast carcinoma who underwent surgery between January 1993 and December 1998. Patients were considered HER-2/neu-positive if they were 3+ on IHC testing. A total of 194 (25.1%) patients with HER-2/neu-overexpressing newly diagnosed breast cancer were identified in our study. The medical records and pathologic data of all 773 patients were reviewed retrospectively. Results: During a median follow-up period of 8.1 years, brain metastasis were identified in 7.2% (14 patients) with 194 HER-2/neu-overexpressing breast cancer compared with 2.6% (15 patients) in 597 HER-2/neu-negative patients (hazard ratio 2.924 [1.385–6.175], P=0.005). More HER-2/neu-overexpressing patients developed distant metastasis (33.5% vs. 18.8%, P=0.0001). The 8-year overall survival was 76.1% for HER-2/neu-negative patients versus 56.4% for HER-2/neu-positive patients (P<0.00001). By multivariate analysis, HER-2/neu overexpression, tumor size larger than 2 cm, at least one positive node, and progesterone receptor (PR)-negativity were independent risk factors for the development of brain metastases. Conclusions: Our data show that HER-2/neu overexpressing early breast cancer patients are at significantly increased risk for brain metastases. Also, our results demonstrate that HER-2/neu overexpression is an important independent prognostic factor of early breast cancer, and suggest that more aggressive adjuvant chemotherapy and radiologic screening to detect brain metastases should be considered in this population. No significant financial relationships to disclose.