Hereditary breast cancer and genetic counseling in young women

Abstract

Introduction It is well established that a family history of breast cancer is associated with an increased risk of developing breast cancer . In fact, among those variables that have been shown to bear a relationship with breast cancer, the highest risk, after age, is the presence of a positive family history of breast cancer [1]. Among breast cancer patients, up to 5% -10% are considered directly related to the inheritance of mutations in BRCA1 or BRCA2 genes [2], which accounts for most hereditary breast cancers. Claus et al. [2] estimated the proportion of breast cancer attributable to inherited autosomal dominant genes to be approximately 33% in subjects aged 20 -29 years. This estimated risk decreased with age at onset to approximately 1.5% of case s ubjects aged 70 years or more. Women carrying these mutations have a lifetime risk of breast cancer of 60% -80% [3] ; therefore, detection of mutations in these two genes can be used as a molecular predictor for breast cancer. At present, data suggest that a mutation in BRCA1 accounts for the majority (80% -90%) of families containing multiple case subjects with breas t and/or ovarian cancer, and approximately 45% of inherited breast cancers [4], whereas a mutation in BRCA2 is thought to account for approximately 35% of inherited breast cancers [3]. Genetic screening As a consequence of current trends in multidisciplinary therapy for breast cancer, BRCA1 and BRCA2 genes are not onl y useful as molecular markers for hereditary breast cancer risk screening, but have also become important indicators for prevention, treatment and prognosis of breast cancer. Screening for BRCA1 or BRCA2 mutations is difficult. In a large proportion of pat ients with breast cancer who have a family history strongly pointing to hereditary disease, a BRCA1 or BRCA2 mutation cannot be demonstrated. This may be partly explained by germline mutations in less common genes other than BRCA1 or BRCA2 , such as in the