Familial Breast Cancer: Detection of Prevalent High-Risk Epithelial Lesions

BRCA1 and BRCA2 mutation carriership is associated with a highly increased risk of developing breast carcinoma. For women carrying a BRCA mutation, the risk of breast cancer begins to increase before the age of 25, with a steep increase after the age of 40 years. The cumulative risk of developing breast cancer before the age of 40 years is ~ 15%, while the cumulative risk of developing breast cancer before the age of 50 is 40–50% (Ford et al., 1998). The life time risk of invasive breast cancer is 60–80%. Very little is known regarding the early stages of breast cancer development in the inherited forms of the disease. Women with hereditary predisposition to breast cancer are prone to develop epithelial lesions that indicate a high risk of subsequent invasive breast cancer (Dupont and Page, 1985; Hoogerbrugge et al., 2003). These high-risk lesions include atypical lobular hyperplasia (ALH), atypical ductal hyperplasia (ADH), lobular carcinoma in situ (LCIS), and ductal carcinoma in situ (DCIS) (Kauff et al., 2003). These epithelial lesions may predict the occurrence of subsequent invasive breast cancer (Singletary, 1994). Women with a clear autosomal dominant family history for breast cancer that is not caused by a BRCA1 or BRCA2 mutation also have a prevalence of epithelial high-risk lesions, which is at least as high as that of mutation carriers. The presence of high-risk lesions is associated with age; especially at the age over 40 years a large number of women with or without a BRCA mutation have high-risk epithelial lesions. Previous oophorectomy should not be taken to indicate low-risk of epithelial lesions in women at high risk of hereditary cancer (Hoogerbrugge et al., 2006). The options for women with a deleterious germ-line mutation in BRCA1 or BRCA2 to handle their high risk are either regular surveillance or prophylactic mastectomy. Bilateral prophylactic mastectomy in healthy women with a BRCA mutation is associated with a 90% reduction in breast cancer incidence (MeijersHeijboer et al., 2001; Rebbeck et al., 2004). When applied at young age, at or before the age of 40 years, this may lead to a significant survival advantage (van Roosmalen et al., 2002). This procedure is much less accepted for women who appeared to be negative for a BRCA mutation even though they have an apparent autosomal 6 Familial Breast Cancer: Detection of Prevalent High-Risk Epithelial Lesions