Women at increased risk for breast cancer would seem to be ideal candidates for chemopreven-tion initiatives; however, the problem of identification of the high-risk woman is far from solved. There is no consensus regarding the level of risk that is clinically relevant. The interactions among risk factors and their variability over time are poorly understood, and most of the data come from studies of white women; thus, little is known about the impact of ethnic diversity. Finally, with the exception of women with predisposing genetic mutations, the majority of women with risk factors will not develop breast carcinoma. A recent study of the fraction of breast cancer cases in the United States attributable to risk factors152 found that fewer than 50% of women who develop the disease have any identifiable risk factors. Family history of breast cancer accounted for only 9% of cases, while relatively minor risk factors, such as later age at first birth and nulliparity, were seen in 29% of cases. In a similar study, Seidman et al.153 noted that only 21% of breast cancer cases in women aged 30-54 and 29% of cases in women aged 55-84 occurred in women with at least one of 10 common breast cancer risk factors. The majority of women had minor risk factors, which increase the RR of breast cancer only twofold, and most had only a single risk factor. This level of increased risk would not meet the entry criteria for the trials of breast cancer prevention in high-risk women discussed below. These data suggest that even if women with a very small increase in breast cancer risk were targeted for prevention initiatives, a large number of cases would continue to be missed. Two strategies have been proposed to reduce the risk of breast cancer: (1) use of tamoxifen in high-risk pre- and postmenopausal women identified with the Gail model154,155 and (2) use of a SERM for the prevention of osteoporosis, which will prevent breast cancer as a side effect in older post-menopausal women.12
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