Hereditary breast and ovarian cancer (HBOC): review of its molecular characteristics, screening, treatment, and prognosis

Abstract

Breast cancer is a common cancer affecting a large number of patients. Notably, 5-10% of all breast cancer patients are genetically predisposed to cancers. Although the most common breast cancer susceptibility genes are BRCA1 and BRCA2, which are also associated with the risk of developing ovarian and pancreatic cancer, advances in next-generation sequencing (NGS) analysis technology enabled the discovery of several non-BRCA genes responsible for breast and ovarian cancers. Studies on hereditary breast and ovarian cancer (HBOC) involve not only determining the predisposition to developing cancer, but also considering the current treatment for breast cancer, prevention of next cancer, risk diagnosis, and adoption of protective measures for relatives. We present a comprehensive review of HBOC, which will be a useful resource in the clinical setting. Many hereditary tumors, including HBOC, are syndromes characterized by the development of different types of cancer in succession. Taking advantage of knowing predisposition of susceptibility to cancer, it is important to continue and update cancer management protocols, which includes the adoption of preventive measures, countermeasures, and treatments, to accurately assess and prevent the impact of cancer on the quality of life of the next generation of patients.

Keywords: BRCA; BRCA1/2 mutations; HBOC; Hereditary breast and ovarian cancer.

Fig. 1

BRCA protein. BRCA1 and BRCA2 are large hub proteins that bind other molecules involved in HR. It has been reported that the phenotype of breast and ovarian cancer differs depending on the location of the mutation (BCCR, OCCR [48])

Fig. 2

Risk assessment for HBOC. HBOC risk assessment is recommended to be comprehensive for all cancer patients instead of the traditional individual approach

Fig. 3

Cumulative risk of breast and ovarian cancer (women). Four studies reported the prevalence of breast and ovarian cancers in women up to the age of 70 [41, 62, 63] and 80 [64] carrying BRCA mutations. Two reports, [62] and [63] are meta-analysis studies, covering 22 and 10 studies, respectively, and [63] is the most extensive prospective study with 3986 BRCA1 and 5066 BRCA2 cancer-free mutation carriers; [41] is the Asian cohort study, involving 108 Korean BRCA1/2 mutation carriers. Data from a large number of prospective studies are desirable for calculating the risk of developing a rare genetic disorder, as family history is prone to bias

Fig. 4

a Results of MGP testing for unselected patients with breast cancer (ATM, BRCA1, BRCA2, CHEK2, PALB2, PTEN, TP53). Genetic prevalence is suggested to differ by cohort background and ethnicity. b PV prevalence (all genes). BRCA2 mutation prevalence is still high in Asian cohorts, even as the number of genes examined increases