is there about pregnancy and lactation that confers protection? Can this be seen in an animal model? Do placental hormones contribute to protection? Beyond these general questions, it has been observed that there is a cyclic difference in both mitogenesis and steroid receptors in the breast when examined using thymidine incorporation and estrogen or progesterone receptor-binding assays, respectively (Anderson et al., 1990). These data suggest additional research questions: What causes increased mitogenesis during the luteal phase? If it is progesterone, what is the mechanism? Is progesterone responsiveness permanently altered by pregnancy and lactation?

Pathological Breast Tissue

Information continues to be needed on both normal and neoplastic tissue. Although the physiology of the breast is relatively well understood, there is still no useful understanding of the transformation from benign to malignant breast epithelium. Pathologists have used biopsy material to identify a small subgroup of women at increased risk, but there is no reason to think that the majority of breast cancers arise from this type of background.

Efforts to determine the effect of oral contraceptives on the risk of developing breast cancer should probably focus on the effect of these agents on normal breast tissue. Cystic conditions—in some instances, gross cystic disease—are common during the reproductive years, and although such tissue might be considered abnormal, recent studies do not reveal an increase in breast cancer in such patients. Further studies of cyst fluid should be conducted because cyst fluid constitutes the best available reflection of breast epithelium. A number of mutagens as well as specific growth factors have been described in cyst fluid. Much of this work focuses on early detection, but it can also be used to investigate hormones that are thought to cause epithelial proliferation in the breast. Both the administration and withdrawal of hormones could be investigated because most women with gross cystic disease form additional cysts. More detailed characterization of breast cyst fluid would be beneficial; once this has been done, the effect of oral contraceptives on a wide variety of biological markers (e.g., gross cystic disease fluid protein) could be determined.

Cysts generally appear during the 30s and 40s; thus, there is also a need for tissue that will provide epithelium from younger women. The best source of such tissue would be fibroadenomas, which are most common between the ages of 15 and 25. These tumors are commonplace but have received little study because they are not associated with cancer. Despite the lack of association, however, efforts



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