Is Cystic Disease Related to Breast Cancer?

Human breast cystic disease is a common premenopausal benign breast condition. Apocrine metaplasia of normal breast epithelium is the lesion that allows cysts to develop. Apocrine metaplasia and breast cysts occur frequently in association with other proliferative changes in breast epithelium, especially breast epithelial hyperpla-sia. Clinical follow-up studies of women with breast cystic disease indicate an increased risk of subsequent development of breast carcinoma. This risk is enhanced when multiple cysts occur. A positive family history of breast carcinoma adds to the increased risk that is associated with breast cystic disease. Biochemical analysis of breast cystic disease fluid shows a unique protein profile. GCDFP-15 (gross cystic disease fluid protein) in breast cystic disease fluid is also found by immunoperoxidase staining to be present in ∼50% of all breast carcinomas. Enhanced production of GCDFP-15 by breast carcinomas has been shown experimentally and clinically with the use of androgens. A hypothesis is presented on the sequence of alterations that relate to the development of breast gross cystic disease and to the development of breast carcinomas with apocrine features.