The pathogenesis of breast cancer, the most frequent female malignancy, entails both genetic and acquired risk factors. Among the various oncogenetic mutations, those involving the BReast Cancer 1 (BRCA1) and BReast Cancer 2 (BRCA2) genes are associated with an extremely high risk of developing breast cancer, with a penetration approximating 70% in women with a positive family history for this malignancy. This important evidence elicits some pragmatic considerations, such as the clinical effectiveness of screening for the most penetrant BRCA mutations in women with or without a positive familial history, but also raises important issues related to the most appropriate clinical management of these patients. Despite it seems now almost certain that BRCA testing should be offered to women with a positive familial history for breast cancer, the balance between advantages and limitations of a population screening remains largely debated. Whatever conclusion can be reach at this point in time must be accurately weighed against at least four different perspectives, which include the low prevalence of these mutations in the general population, the relatively lower risk of developing breast cancer in women without a familial history for this malignancy, the direct and indirect cost of genetic testing and, last but not least, the many potential psychological and clinical consequences in patients receiving a positive test result. Many of these still unresolved issues will be tentatively discussed in this article.
Keywords: Breast cancer, BRCA, BReast Cancer 1 (BRCA1), BReast Cancer 2 (BRCA2