Translational approaches for the prevention of estrogen receptor-negative breast cancer.

Breast cancer prevention has focused heavily on endocrine interventions using selective estrogen receptor modulators and aromatase inhibitors. Tamoxifen, the stereotypical selective estrogen receptor modulator, significantly reduces the breast cancer incidence in high-risk women. Selective estrogen receptor modulators and aromatase inhibitors, however, only prevent the development of estrogen receptor-positive breast cancer and have no effect in reducing the risk of estrogen receptor-negative breast cancer, which has poor prognosis. Thus, preventive therapies for estrogen receptor-negative breast cancer are clearly needed. Recently, a number of novel chemopreventive agents targeting nonendocrine pathways have been developed and shown to prevent estrogen receptor-negative mammary tumorigenesis in animal models. These agents include rexinoids, selective cyclooxygenase-2 inhibitors, tyrosine kinase inhibitors, and others. In this review, we discuss the effects of selective estrogen receptor modulators and aromatase inhibitors, as well as novel agents targeting nonendocrine pathways. We also discuss the promise of combining these agents for the effective prevention of all forms of breast cancer.