The overall aim of this research is to better understand the role of cell proliferation in determining risk of breast cancer in human populations. We hypothesize that a number of well known risk factors for breast cancer operate by modulation of the proliferation and differentiation of normal breast epithelial cells and, in many instances, this is realized through modulation of levels of steroidal hormones. The goals of this research are to directly examine the effects and possible interactions between factors which putatively mediate proliferative response and to relate these factors and direct measures of proliferative activity in normal breast epithelium to occurrence of breast cancer. These goals lead to the following specific aims: 1. To measure cell proliferation by immunocytochemistry in normal breast epithelial cells and to relate this measure to serum levels of steroidal hormones, to immunocytochemical expression of hormone receptors, growth factors, growth factor receptors and oncogenes in normal breast epithelium, to age, menopausal status and day of menstrual cycle (for premenopausal women), and to epidemiologic risk factors for breast cancer. 2. To compare measures of cell proliferation in normal breast epithelial cells of women diagnosed with breast cancer to those in women diagnosed with benign breast disease. 3. To compare serum levels of steroidal hormones among women diagnosed with breast cancer to those among control women. 4. To compare serum levels of steroidal hormones and immunocytochemical expression of hormone receptors, growth factors, growth factor receptors and oncogenes in normal breast epithelium among women diagnosed with breast cancer to that among women diagnosed with benign breast disease. We will accomplish these aims by conducting an Individually matched vested case-control study within the cohort of 300,000 women participating in the Shanghai Breast Self-Examination Trial. Breast biopsy specimens will be obtained from 330 incident cancer cases and from 1000 incident cases of benign breast disease. Immunocytochemical methods will be used to measure cell proliferation, hormone receptors, growth factors, growth factor receptors and oncogenes In epithelial cells within the breast lesion and in normal cells adjacent to the lesion. Serum levels of steroidal hormones and questionnaire data will be obtained from these individuals and from 660 control women who will be individually matched to the cancer cases on age, menopausal status and, in premenopausal women, day of menstrual cycle on which the serum specimen is collected.
