Studies of Breast Cancer Chemoprevention in Human High-Risk Primary Cells and Genetically Engineered Mouse Models

Abstract

BRCA1 mutations have been associated with a 50-80% increased risk of developing breast cancer by the age of 70. Current recommendations for women carrying BRCA1 mutations include risk-reducing surgeries. Chemoprevention has been proposed as an option for these women. However, extensive research on the efficacy of these therapeutics is currently lacking due to the underrepresentation of women carrying BRCA1 mutations within clinical studies. Mouse models and primary cell culture of mammary epithelial cells serve as viable tools to study the efficacy of both estrogen-related hormonal and nonestrogen-related hormonal interventions in controlled settings. Here, studies using genetically engineered mouse models were employed to investigate the effectiveness of tamoxifen, raloxifene, letrozole, and efatutazone as chemopreventives strategies to reduce mammary cancers. Within mouse models, both estrogen-related hormonal and nonestrogen-related hormonal preventatives significantly reduced preneoplastic lesions but failed to eradicate disease. An in vitro system using high-risk for breast cancer human primary mammary epithelial cells was established to study estrogen-related hormonal response. Heterogeneity between samples was found with differences in estrogen-related hormonal response alluding to differences between response in women being conserved in vitro.