ABSTRACT
PURPOSE: Germline mutations of the BRCA2 gene are involved in the development of a considerable number of male breast cancer cases. Although phenotypic differences have been observed between sporadic and BRCA-related breast carcinomas, conflicting data exist on the differences in prognosis of women with hereditary and sporadic breast cancer. The purpose of the study was to investigate the prognostic value of BRCA2 status in male breast carcinoma (MBC). EXPERIMENTAL DESIGN: We studied 43 male breast cancer patients, including 12 with BRCA2 mutations. Tumor samples were characterized immunohistochemically using antibodies to estrogen receptor, progesterone receptor, and androgen receptor (AR). RESULTS: BRCA2-related tumors presented at the earlier age compared with sporadic tumors (P = 0.005). Patients positive and negative for BRCA2 mutations did not differ with respect to tumor size, lymph node involvement, histological grade, and sex hormone receptor status. Five-year disease-free survival (DFS) and overall survival (OS) were significantly decreased in BRCA2-positive patients (67% versus 28% for BRCA2-negative versus positive patients, respectively, P = 0.017 for DFS; 86% versus 25%, P = 0.006 for OS). Shorter survival was also correlated with expression of AR in tumor tissue (74% versus 33% for patients with tumors staining negatively and positively for AR, P = 0.029 for DFS; 71% versus 57%, P = 0.05 for OS). CONCLUSIONS: The BRCA2 mutations and AR expression in tumor tissue are independent adverse factors for MBC prognosis. BRCA2-related MBC presents at the earlier age compared with non-BRCA2-related cancer, but do not differ with respect to other clinicopathological features.
Subject(s)
BRCA2 Protein/genetics , Breast Neoplasms, Male/genetics , Breast Neoplasms, Male/metabolism , Mutation/genetics , Receptors, Androgen/metabolism , Adult , Aged , Aged, 80 and over , Breast Neoplasms, Male/diagnosis , Carcinoma, Ductal/diagnosis , Carcinoma, Ductal/genetics , Carcinoma, Ductal/metabolism , Carcinoma, Intraductal, Noninfiltrating/diagnosis , Carcinoma, Intraductal, Noninfiltrating/genetics , Carcinoma, Intraductal, Noninfiltrating/metabolism , Carcinoma, Lobular/diagnosis , Carcinoma, Lobular/genetics , Carcinoma, Lobular/metabolism , Disease-Free Survival , Exons/genetics , Humans , Immunoenzyme Techniques , Lymph Nodes/pathology , Lymphatic Metastasis/diagnosis , Lymphatic Metastasis/genetics , Male , Middle Aged , Predictive Value of Tests , Receptors, Estrogen/metabolism , Receptors, Progesterone/metabolism , Survival RateABSTRACT
Over the years the incidence of malignant melanoma in Poland as well as in other countries has been continuously increasing. Surgery is a treatment of choice in the early stages of primary lesions. Advanced malignant melanoma however is resistant to chemotherapy or radiotherapy. Therefore there is a need for new, more effective treatments. In the last years biotherapy such as immunotherapy is focusing a lot of attention. Unfortunately, systemic administration of immunostimulatory factors is very often associated with severe side effects. Thus, concepts of specific immunotherapies such as immunogene therapy have been developed. Currently, various gene therapy strategies of malignant melanoma are being evaluated in multiple clinical trials carried out all over the world. They include gene modified cancer vaccines (GMTV) modified with genes encoding (i) cytokines or (ii) costimulatory molecules and dendritic cells modified with (iii) genes encoding tumor antigens or (iv) immunostimulatory factors. Since January 1996 in Department of Cancer Immunology USOMS, at GreatPoland Cancer Center in Poznan, Poland a GMTV has been tested in malignant melanoma patients. For the last 6 years more than 220 patients were enrolled into study of GMTV consisting of melanoma cells modified with genes encoding IL-6 and its agonistic soluble receptor (sIL-6R). More than 25% of objective clinical responses and significant life extension were observed. The encouraging results formed a basis for design of a phase III prospective, randomized clinical study.