Basic research in the biology of the breast is identified by the committee as a priority. As one author (McCarty, 1989) notes, “That so much effort has been concentrated on the study of the abnormal with so little knowledge of normal physiology is an aberration. . . . One is struck by the paucity of existing understanding of ‘normal ' breast development, and the myriad factors influencing the proliferation of normal breast epithelium.”
Research is especially needed on the transition from normal to abnormal growth—including, for example, research on the role of local growth factors and newly detected extracellular matrix proteins, estrogen metabolism (e.g., the products of the 16α-hydroxysteroid metabolic pathway), and oncogenes. As basic resources for this research, in vitro model systems that employ normal breast tissue are needed, in which the effects of contraceptive steroids can be directly examined.
Epidemiological research priorities include a large, case-control (retrospective) study with sufficient statistical power to resolve the assessment of small increases in relative risk of breast cancer. One such study is currently being conducted by the National Cancer Institute; it involves primarily women below the age of 45. A study of postmenopausal women—who experience the bulk of breast cancer— is needed to elucidate the effects of both oral contraceptive use alone, and oral contraceptive use followed by hormone replacement therapy. As oral contraceptive formulations and use patterns of the pill change, future case-control studies will be required; the committee has outlined seven strategies that are likely to improve these future studies (see Chapter 2). The launching of appropriate, cost-effective new cohort (prospective) studies is equal in priority to the conduct of case-control studies. There are no substitutes for analytical, observational epidemiological studies in resolving the relationship of oral contraceptives and breast cancer, and great attention should be given to identifying the organizational settings (e.g., health maintenance organizations) in which they can be implemented. Efforts must also be made to establish coordinated international plans (particularly American-British plans) for case-control and cohort studies to monitor the long-term safety of current and widely used new formulations.
Biological markers, as they become more generally available, should be incorporated into epidemiological protocols. Consistent with a multidisciplinary approach to better understanding of the causes of breast cancer, there is a need for research that uses biological markers within the context of epidemiological study designs, using innovative as well as traditional research tactics.