Expression of BRCA1, HER-1

Background: The BRCA1 caretaker gene is associated with poor prognostic features in hereditary breast cancer and may also play a role in sporadic breast cancer (SBC). HER-1 and HER-2 overexpression is associated with adverse prognosis in SBC. We studied whether BRCA1 expression was associated with HER1, HER2 and other prognostic features in SBC. Patients and Methods: Fifty newly-diagnosed SBC patients were studied for prognostic features and immunohistochemical expressions of BRCA1, HER-1 and HER-2. Results: Tumors were positive for BRCA1 in 26%, HER-1 in 32% and HER-2 in 20% of cases. Lack of BRCA1 expression was associated with node metastases and decreased estrogen receptor. HER-2 expression was associated with young age, HER-1, Ki67 and decreased hormone receptors. No correlation was observed between BRCA1 and HER-1 or HER-2. Conclusion: In SBC, the lack of BRCA1 expression was associated with poor prognostic features, but unrelated to HER-1 and HER-2. HER2 and HER-1 were, however, highly correlated. BRCA1 was isolated by positional cloning methods as a gene linked to breast cancer in families with a pattern of autosomal dominant inheritance of the disease (1). Inherited BRCA1 breast cancer is associated with poor prognostic features and decreased survival (2, 3). The product of the BRCA1 gene is a 220-kD a nuclear phosphoprotein that has been implicated in the regulation of cell proliferation, cell cycle progression, apoptosis, DNA repair and recombination (4). These functions of BRCA1 support the role of BRCA1 as a tumor suppressor gene, or more precisely as a "caretaker gene", since it is involved in genome integrity maintenance (5), therefore raising the question of the role of BRCA1 in sporadic breast cancer. HER-1 was the first identified of a family of receptors known as the HER family or ErbB tyrosine kinase receptors. This receptor family comprises four homolog receptors: HER-1 (also called EGFR, ErbB-1), HER-2 (HER2/neu, ErbB-2), HER-3 (ErbB-3) and HER-4 (ErbB-4). Expression of HER-1 and overexpression of HER-2 are associated with poor prognosis in breast cancer patients (6). Particular interest in the HER family comes from the demonstration of improvement in overall survival in advanced HER-2-overexpressing breast cancer using antiHER-2 monoclonal antibody (7), and the development of promising inhibitors of HER-1 (8). Few studies have explored the potential association of HER family expression with BRCA1. Information currently available only concerns BRCA1 inherited breast cancer and HER-2 and remains inconclusive, with findings of no association or an inverse correlation between BRCA1 gene mutation status and the amplification of the HER-2 gene (9-12). The aim of the present study was to explore, in the setting of sporadic breast cancer, the potential link between BRCA1, HER-1 and HER-2 expressions and their relationships with other clinicopathological prognostic features. 4535 Correspondence to: Yan Ansquer, Hôpital Louis Mourier, Service de Gynécologie Obstétrique, 178 rue des Renouillers, 92 701 Colombes Cedex, France. Tel: 00 33 1 47 60 63 40, Fax: 00 33 1 47 60 63 38, e-mail: yan.ansquer@lmr.ap-hop-paris.fr