Apoptotic cell death is the physiologic counterpart of cell proliferation in regulating cell number within tissues and organs and also occurs prematurely in response to anti-cancer agents and the effects of some oncogenes. The study of cancer cells suggests that dysregulation of apoptosis is an important target in carcinogenesis. This study will examine the role of apoptosis in the development of breast cancer. We propose to use the cases and controls in the ongoing project Cell Proliferation and the Epidemiology of Breast Cancer, a large population- based study examining the influence of cell proliferation on breast carcinogenesis. Molecular investigation of the control of apoptosis has defined the role of the cell death-regulating genes bcl-2, bax, and bcl-x in mammalian cells. We will also examine the expression of these cellular proteins in relation to breast cancer risk and measures of apoptosis in this population. Finally, we will use the measures of cell proliferation and factors related to cell proliferation from CPEBC Project to determine relationships between these variables and apoptotic death, in order to understand the regulation of this fundamental process.