Validation of a Pre-Clinical Model for the Investigation of Menarcheal Age on Breast Cancer Risk

Individuals with late menarche have breast cancer rates that are approximately 2 fold lower than individuals with early menarche, however the mechanism of protection is unknown. Two theories dominate the model of breast tissue aging proposes that cumulative lifetime exposure to circulating ovarian hormones determines risk. The second theory suggests that early menarche is associated with persistent qualitative differences in the hormone axis or in the gland itself. Purpose Determine whether an extensively utilized preclinical model for human breast cancer, the SD rat model, demonstrates the relationship between age of sexual maturation and mammary cancer risk that is observed in humans. Aims 1 Determine the relationship between age at vaginal opening VO, a marker for ovarian function, and susceptibility to MNU-induced mammary cancer and 2 investigate the hypothesis that early sexual maturation confers increased breast cancer risk by persistently altering systemic hormone levels andor by altering the response of the gland to subsequent hormone stimulation. Methods Sexually immature female SD rats, monitored for VO, will be separated into Gp 1, the first 25 of rats to reach VO and Gp 2, the last 25 to reach VO. Effect of age of VO on estrous cycling, mammotrophic hormone levels, ER and PR expression in the mammary gland, exogenous hormone stimulation, and susceptibility to mammary carcinogenesis will be determined. Relevance Once characterized, this pre-clinical model can be utilized by the breast cancer community to investigate the mechanisms by which early menarche increases breast cancer risk.