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RESEARCH PRODUCT

The Genetics of Breast Cancer

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Breast cancer (BC) is a complex and heterogeneous disease caused by interaction of both genetic and nongenetic risk factors. The biological diversity of sporadic BCs consists in the development of several BC subtypes, which are systematically different from one another and which present specific genetic and phenotypic features. Recently, with the advent of cDNA microarrays it has been possible to associate a distinctive “molecular portrait” to a single BC subtype and, consequently, improve BC taxonomy. From a clinical point of view, the gene expression profiles could supply the classic pathological experiment with the aim to select patients with a better prognosis and that could have a benefit from a specific chemotherapy treatment. Recently a new role in BC progression has been identified in a group of small, noncoding RNAs, the MicroRNA (miRNA), which regulate gene expression. Of particular interest is the identification of different miRNA expression levels according to the five molecular BC subtypes identified by experiments on microarray gene expression. About 3–8% of all breast cancers are hereditary, and it is estimated that the main contributors to this type of cancer are mutations in autosomal dominant genes segregating with the disease. Nowadays, BRCA1 and BRCA2 are considered as the two main BC susceptibility genes, although the involvement of additional low penetrance genes implicated in particular syndromes should not be overlooked. Epidemiologic studies reported that women who are BRCA1 mutation carriers have a 45–60% cumulative risk to develop BC before age 35–40, and the average cumulative risk in BRCA1-mutation carriers by age 70 years is 65% whereas the corresponding risk to develop this neoplasm for BRCA2 mutation carriers is estimated to be 25–40% and 45%, respectively. Oncogenetic counseling requires a “multidisciplinary approach,” involving geneticists, oncologists, and psychologists and is offered by many diagnostic clinical genetic services. Nowadays, risk evaluation regarding BC patients is performed with the use of specific mathematical models, such as BRCAPro, the Couch and the Myriad models.