We propose to evaluate the subcategories of benign breast disease that are associated with elevated risk of breast cancer. In addition, using prospectively collected data on established risk factors for breast cancer as well as a variety of nutritional factors, we will investigate the potential interactions with the subcategories of benign breast disease. In particular, we will examine interactions between benign breast disease and family history of breast cancer, parity, age at first birth and at menopause and relative weight (weight/height2). Dietary factors to be examined include alcohol intake, dietary fat intake, intake of vitamin A (preformed and carotene), vitamin E, and caffeine. The proposed study is a nested case-control study within the Nurses' Health Study, a cohort of 121,700 US female registered nurses, currently aged 40-65 who were enrolled in a prospective study of risk factors for breast cancer in 1976 and who have been followed with biennial questionnaires since then. (Follow-up of this cohort has been 95.4% for non-fatal outcomes and 98.25% for fatal outcomes.) A semi-quantitative food frequency questionnaire administered in 1980 enables us to assess the dietary variables. We propose to obtain histopathology slides from 256 women with breast cancer and a history of an earlier biopsy for benign breast disease and 1024 controls randomly selected from among women with a history of biopsy for benign breast disease in the cohort. Slides will be independently reviewed in a blinded fashion by two pathologists and graded according to a uniform classification system based on that of Page. The relative risk of breast cancer associated' with subcategories of benign breast disease (nonproliferative, proliferative, atypical) will be calculated using the women with no history of benign breast disease in the Nurses' Health Study cohort as a reference group. Potential interactions with epidemiologic and dietary risk factors will be assessed by evaluating relative risks within levels of these factors.
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