All women are at risk of breast cancer, with one in eight developing the disease within their lifetime. The breast surgeon is going to see a wide array of women, each one at a dif­ferent risk of developing cancer, or in some cases a second cancer. Knowing that risk will impact several decisions, including when and how to begin screening, whether an abnormal finding should be biopsied or observed, the best course of treatment for a woman diag­nosed with cancer, implications for family members, and when a woman without breast cancer may benefit from chemoprevention or prophylactic surgery. In addition, many patients concerned about cancer will have many questions regarding things they can do to decrease their risk.

Family history is clearly an important risk fac­tor. Familial clustering of breast cancer has long been recognized, with the greatest risk in women with a first-degree relative with early-onset breast cancer. However, only 10% of women diagnosed with breast cancer have a positive family history. It should be empha­sized with women that the absence of a family history does not mean that breast cancer is not a concern. Likewise, not all women with a rel­ative who had breast cancer are at the same increased risk. The risk increases with the age of the patient, the age of the relative, the num­ber of relatives with cancer, and the relation between the subjects (e.g., first degree, second degree). For example, in a metaanalysis using data from 150,000 women, the risk of breast cancer was increased three times for a woman who had a relative with breast cancer before age 30, but only 1.5 times if the relative was diagnosed after age 60. As another example, women with one affected first-degree relative had a risk 1.8 times that of their counterparts, whereas women with two affected first-degree relatives saw risk increase threefold.

The chance of finding a mutation in BRCA1 or BRCA2 increases with the number of family members who have had breast or ovarian can­cer, the number of relatives who have had mul­tiple cancers, and the younger age when family members developed cancer (Table 8–2). A detailed family history on both the paternal and maternal sides should be obtained, record­ing any malignancies (not just breast or ovar­ian cancer), the age when the malignancy occurred, and in the case of breast cancer, whether the cancer was bilateral. A useful tool to predict the likelihood of an individual having a deleterious BRCA mutation is a com­puterized program BRCAPRO, which incor­porates six predictive models for inherited breast cancer. This program is available free of charge at http://www.cancerbiostats.onc.jhmi.

Li-Fraumeni syndrome is an autosomal domi­nant condition characterized by the devel­opment of multiple tumors. Families have

The association between reproductive factors and breast cancer risk centers on exposure to hormones, primarily estrogen. This is sup­ported by observational data, epidemiologic studies, animal models, and the clear evidence of risk reduction by decreasing estrogen levels. So it is reasonable to believe that measuring serum estrogen levels would identify high-risk individuals. However, the correlation between breast cancer risk and the levels of hormones in the blood have not been consistent. Part of this is due to difficulties with the assays. More responsible is the large variability between patients, and within individuals, of hormone concentrations. Estrogen levels fluc­tuate during the menstrual cycle, so studies of premenopausal women, particularly when only one blood sample is used, are difficult to interpret. The data are clearer for postmeno­pausal women, in whom multiple prospective epidemiologic studies have found a positive relationship between serum estradiol concen­tration and breast cancer risk. The association is strongest when looking at ER- and PR­positive tumors.