BOX 2-7 Determining Susceptibility to Breast Cancer of Early Onset
For some years it has been inferred that a heritable gene that predisposes women to breast cancer is responsible for about 5 percent of cases-specifically the rare inherited form that strikes women in their thirties and forties. Approximately one woman in 200 inherits the defective gene, and those who do face an 80 to 90 percent risk of developing the disease. The same altered gene seems also to predispose to ovarian cancer. Identification of this gene could lead to new methods for detection far earlier than is currently possible, with the advantage of earlier and more aggressive treatment. Linkage studies in affected families are already providing some women with predictive tests. Current technology is available in some large families to identify family members at risk for breast cancer by testing DNA markers co-segregating with the cancer gene. For early detection of the gene to be beneficial, individuals carrying the inherited cancer gene may need, in the future, to undergo further periodic screening using biomarker approaches in the target organ. At the present time, women at risk can be closely monitored with physical examinations and mammograms for signs of malignancy. Presented with the options, however, many will choose bilateral preventive prophylactic mastectomy and often also removal of their ovaries after completion of childbearing as a preventive measure.
The development of this predictive test has raised numerous questions regarding wide-scale screening and testing (Marshall, 1993). It is currently impossible to identify women at high risk of inherited breast cancer by general population screening. Identification of the normal and mutant sequence(s) of the critical susceptibility gene(s) would be necessary for this purpose. For now, testing is limited to large families at risk. With anticipated discovery of the gene(s) in the near future, however, it is conceivable that efforts would be made to screen the general population. The psychosocial consequences of receiving such loaded information have not yet been fully evaluated, nor has the effect of such information on insurability. Pilot studies will be needed to determine to whom the test should be offered, including where and when. Current research protocols provide intensive counseling by genetic counselors and physician geneticists. This process is very costly and may not be feasible economically or in terms of available trained personnel if largescale genetic screening interventions in breast cancer or other forms of cancer are developed.