The ER/PR status of the originating cell of ER-negative breast cancer

Estrogen signaling is required for proliferation of all normal mammary epithelial cells; yet prophylactic blockage of estrogen signaling fails to prevent breast carcinogenesis in 30% of the patients that otherwise would develop breast cancer. Studies in germline mouse models have shown that loss of estrogen signaling blocks carcinogenesis in mammary cells that have lost p53 or gained an oncogene such as ErbB2. However, we find that in a somatic mouse model that more closely mimics the evolution of sporadic human breast cancers, mammary epithelial cells that have gained PyMT or ErbB2 evolve into tumors independent of estrogen or other ovarian functions. Our data suggest that prophylactic estrogenic therapy cannot prevent carcinogenesis in mammary epithelial cells that gained certain genetic alterations, especially those encoding co p