Abstract P2-04-03: A robust transgenic mouse model to study male breast cancer.

Abstract

Abstract Male breast cancer accounts for about 1% of all breast cancers and even though it is a rare disease, the incidence rate has increased steadily during the past 20 years. Study of the male form of the disease has been hampered by a lack of relevant animal models as it is commonly believed that male mammary glands do not contain ducts. Female FVB C3(1)-SV40Tag transgenic mice spontaneously develop hyperplastic mammary lesions that progress to invasive mammary tumors, whereas most of the transgenic males develop prostatic hyperplasia that progresses to adenocarcinoma. However, upon closer examination, we discovered that approximately 45% of transgenic males develop mammary tumors by 40 weeks of age, often prior to developing prostate tumors. The course of male mammary development is similar to that observed in the females but with a later onset. Hyperplastic ducts form as early as 15 weeks of age and progress into DCIS-resembling tumors before developing into invasive tumors that invade locally into adipose tissue and muscle and occasionally form metastases to lung and other organs. We then examined male mammary development in the FVB background strain (wild type) and showed that all males develop mammary ducts that continue to grow and branch throughout adulthood. The morphology of these ducts was similar to that of females with a central lumen surrounded by concentric layers of luminal epithelium, myoepithelium, a basement membrane and surrounding stroma. A study of CD1 male mice confirmed that male mammary development was not specific to the FVB strain but rather, CD1 males showed similar mammary ductal development. Male mammary development in FVB wild type animals and tumor progression in the transgenic males was characterized in terms of cell proliferation, apoptosis and expression of various markers of differentiation including hormone receptor status. In summary, our results demonstrate that FVB C3(1)-SV40Tag transgenic males represent a highly robust and reproducible model for the study male breast cancer. Our long-term goal is to leverage the information we uncovered through this effort to design novel therapies for breast cancer treatment in men. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-04-03.