HER3 expression in the primary tumor as marker of metastatic potential in breast cancer patients.

Abstract

e21033 Background: Breast cancer (BC) is the most common cancer related cause of death in women. Therefore, identification of novel prognostic markers is an important field of research. Recently, HER3 expression was postulated as risk factor for metastatic spread to the brain. We aimed to analyze the predictive value of HER3 expression in patients with metastatic BC treated between 1993 and 2010 at the Medical University of Vienna. Methods: Patients of each subtype (luminal, HER2 positive, triple negative) with metastatic breast cancer were identified from a breast cancer data base. Tissue of the primary tumor was raised from a breast cancer bio-bank. Immunohistochemical staining of estrogen-receptor, progesterone-receptor, HER2 and HER3 was performed. Chi2 test was used to correlate two factors. Overall survival (OS) and time to progression (TTP) were estimated using the Kaplan-Meier method. Results: A total of125 patients (39 luminal, 42 HER2 positive, 44 triple negative) with metastatic BC were available for this analysis. 71 patients (56.6%) had visceral metastases and 67 patients (46.4%) had brain metastases. 7.4% of specimens showed a positive, uniform, intense membranous staining of > 30% of invasive tumor cells (Her3 3+). Less intense, incomplete, membranous staining was observed in a further 34.4%. HER3 expression in the primary tumor did not correlate with BC subtype (luminal 12.8%; HER2 positive 2.4%; triple negative 6.8%; n.s.; Chi2 test). Furthermore, no correlation with the likelihood of developing brain metastases (5% vs. 9.8%; n.s.; Chi2 test) or visceral metastases (7.3% vs. 7.7%; p:n.s.; Chi2 test) was found. Counter intuitively, patients with HER3 overexpression in the primary tumor had a significantly longer TTP (21 vs. 47 months; p=0.03; log rank test) and a trend towards longer OS was observed as well (53 vs. 112 months; p=0.073; log rank test). Conclusions: In contrast to previous reports, we could not validate that HER3 expression predicts for metastatic potential in general and also with regard to brain metastases of BC in a population that was equally distributed between BC subtypes. Further studies are therefore needed to evaluate the prognostic value HER3 expression in BC.