Hereditary breast and ovarian cancer

Familial breast cancer was first recognized in the Roman medical literature of 100 AD [1]. The first documentation of familial clustering of breast cancer in modern times was published by Broca, who reported 10 cases of breast cancer in 4 generations of his wife’s family [2]. In the middle of the nineteen nineties it was proven at the molecular level that a substantial number of breast and ovarian cancers has hereditary monogenic aetiology [3, 4]. Evaluation of frequency of pedigree-clinical signs characteristic for strong aggregations of breast/ovarian cancers among consecutive cases of cancers of these organs as well as analyses of cancer incidence in monozygotic twins indicate that about 30% of breast and ovarian cancers develop because of a strong genetic predisposition [5]. In other breast/ovarian cancers the significance of genetic factors was underestimated. However, recently it has been possible to show the characteristic constitutional background influencing development of cancer also in patients with sporadic neoplasms. Therefore now scientists think that in almost all patients with cancer a certain genetic background should be detectable, although influencing cancer risk to a various degree. Genetic abnormalities strongly related to cancer are called high risk changes (genes) and abnormalities influencing cancer development to a lower degree are called moderate risk changes (genes). Most frequently strong genetic predisposition to breast/ovarian cancers are related to mutations in the BRCA1 and BRCA2 genes and most often it appears as syndromes of hereditary breast cancer – site-specific (HBC-ss), hereditary breast-ovarian cancer (HBOC) and hereditary ovarian cancer (HOC). In family members of families with HBC-ss syndrome only breast cancers but not ovarian cancers are observed. In HBOC syndrome families both breast and ovarian cancers are diagnosed, and in HOC syndrome only ovarian but not breast cancers are detected. Operational clinical-pedigree criteria which we use in order to diagnose “definitively” or “with high probability” the discussed syndromes are summarized in Table 1. In the vast majority of cancer cases related to moderate risk genes family history is negative. HBC-ss, HBOC and HOC syndromes are clinically and molecularly heterogeneous. Mutations in the BRCA1 and BRCA2 genes are the most frequent cause of these syndromes.