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.

Single-Strand Annealing in Cancer

“…The mammalian BRCA1 and BRCA2 genes have their orthologs in lower organisms, which suggests their fundamental and likely tissue-specific functions [ 73 ]. BRCA deficiency (BRCAness) underlined by germline mutations in the BRCA1/2 genes is typical for hereditary breast and ovarian cancers but also occurs in sporadic cases of these and other tumors [ 74 ]. The involvement of the BRCA1/2 genes in cancer pathogenesis is assumed to be associated with their role in maintaining genomic stability in DNA repair, cell cycle regulation, and apoptosis [ 75 ].…”

Recent Advances in Integrative Multi-Omics Research in Breast and Ovarian Cancer

“…Despite the inherent differences in clinical manifestation between breast and ovarian cancer, a portion of these malignancies are intrinsically linked, as women with specific inherited germline mutations including BRCA1, BRCA2, PALB2, TP53, CDH1, and PTEN have an increased lifetime risk of developing either disease [ 64 , 65 ]. BRCA1 or BRCA2 mutations are the most prevalent cause of high penetrance inherited breast or ovarian cancers and have been shown to affect patients irrespective of race or ethnicity.…”

“…However, it is estimated that 39–63% of women with a BRCA1 mutation will develop ovarian cancer while 46–87% will develop breast cancer by age 70. Likewise, BRCA2 mutation carriers are strongly predisposed to develop ovarian (17–27%) or breast (38–84%) cancer [ 65 , 74 , 75 , 76 , 77 ]. Clinically, BRCA1/2-mutated breast tumors tend to be classified as TNBC invasive ductal carcinoma with high nuclear grade while BRCA1/2-mutated ovarian tumors are predominantly classified as HGSOC [ 78 , 79 , 80 ].…”

“…Clinically, BRCA1/2-mutated breast tumors tend to be classified as TNBC invasive ductal carcinoma with high nuclear grade while BRCA1/2-mutated ovarian tumors are predominantly classified as HGSOC [ 78 , 79 , 80 ]. Although BRCA-mutated breast and ovarian tumors are often highly aggressive, a number of studies suggest that these patients may achieve a slightly better short-term therapeutic response (2–3 year overall survival) compared to patients with wild-type BRCA1 or BRACA2, as these tumors may be more responsive to DNA-damaging drugs; however, long-term survival and/or progression-free survival differences remain unclear [ 65 , 79 , 80 , 81 , 82 ].…”

Histone Monoubiquitination in Chromatin Remodelling: Focus on the Histone H2B Interactome and Cancer

“…Germline mutations in BRCA1 are well known to increase the risk of developing breast and/or ovarian cancer, with somatic mutations of this tumour suppressor also identified in sporadic tumours [ 145 , 146 , 147 , 148 , 149 , 150 , 151 ]. The BRCA1 Associated RING Domain 1 (BRCA1-BARD1) heterodimer is one of a number of E3 ligase complexes reported to write H2Bub1 [ 19 ].…”