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Abstract
Hereditary breast and ovarian cancers are the most common familial cancers. At least 10 % of breast cancers (BC) and approximately 20–30 % of ovarian cancers (OC) are caused by inherited genomic defects. The most studied highly penetrant genes associated with breast and ovarian cancer are BRCA1 and BRCA2, key components of the DNA double-strand break repair system. In some patients, the occurrence of breast or ovarian cancer can be explained by mutations in other genes responsible for genome stability: PALB2, CHEK2, BLM, FANCM, RECQL, MRE11, RAD51C, RAD51D, ATM, NBN, CDH1, TP53 and others. It is worth noting that about half of breast and ovarian cancer cases with signs of familial predisposition still have no genetic explanation. Tumour development in heterozygous carriers of pathogenic mutations is usually due to a two-hit mechanism, i.e. somatic inactivation of the 'normal' copy of the gene. An alternative variant of pathogenesis is constitutive suppression of the function of the affected gene (haploinsufficiency), which increases the likelihood of malignant transformation. Initially, studies of familial breast and ovarian cancer were mainly aimed at early diagnosis and prevention. To date, there is growing evidence that hereditary cancers often have molecular targets for targeted therapies. For example, the presence of inherited BRCA1/2 defects is associated with sensitivity to PARP inhibitors and platinum-based drugs. This review presents current information on the genetic mechanisms of predisposition to BC and OC and outlines the main approaches to diagnosis and treatment of this group of diseases.
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