BRCADefekte

BRCADefekte refers to mutations or functional defects in the BRCA1 and BRCA2 genes that disrupt homologous recombination, the error-free repair pathway for double-strand DNA breaks. Defects in these genes lead to genomic instability and markedly increase the risk of several cancers, most notably breast and ovarian cancer, as well as pancreatic and prostate cancers. The BRCA proteins act as tumor suppressors, helping to maintain genomic integrity by coordinating DNA repair and replication fork stability. Inherited BRCA1/BRCA2 mutations are typically passed in an autosomal dominant pattern with variable penetrance, and they account for a substantial portion of hereditary breast and ovarian cancer syndromes. Most pathogenic variants are germline, but BRCA defects can also occur somatically within tumors.

Diagnosis of BRCADefekte usually involves genetic testing based on personal and family history, using sequencing to detect small variants and additional methods to identify large rearrangements. Results are categorized as pathogenic, likely pathogenic, variants of uncertain significance, or benign. Identification of BRCA defects informs cancer risk assessment and guides management.

Management includes enhanced cancer surveillance, risk-reducing surgeries such as bilateral salpingo-oophorectomy or mastectomy in selected individuals, and chemoprevention in some cases. Treatment of BRCA-defective cancers often relies on DNA-damaging agents like platinum chemotherapy and, more recently, PARP inhibitors (e.g., olaparib, niraparib), which exploit the homologous recombination deficiency to kill tumor cells.

See also: homologous recombination deficiency, PARP inhibitors, hereditary breast and ovarian cancer syndrome.