The investigators hypothesize that appearance of a "hyper-sensitive" ER variant might be one of the earliest genetic events in breast cancer evolution, and as such might be an early biomarker useful for the early detection and ultimate prevention of breast cancer. This hypothesis will be tested via three Specific Aims: (1) To study the function of the hyper-sensitive ER variant using estrogen-responsive mammalian expression vector systems; (2) To determine whether expression of the hyper-sensitive ER variant is associated with early breast disease and with breast cancer evolution and progression in breast specimens from several clinical studies;. (3) To determine whether the hyper-sensitive ER variant acts as a promoter or facilitator of mammary carcinogenesis in transgenic mouse models.