[Hereditary breast cancer : Syndromes, pathology, clinical aspects]

Approximately 5-10% of all breast cancers arise from a hereditary predisposition. In addition to the high-risk genes BRCA1 and BRCA2, other genes involved in homologous recombination repair (including PALB2, ATM, CHEK2, RAD51C/D, BARD1) and genes associated with classic tumor predisposition syndromes (TP53, PTEN, STK11, CDH1, NF1) are associated with an increased risk of breast cancer. In addition, polygenic risk contributes to the individual probability of developing the disease through the additive effect of numerous low-penetrance variants.Pathology can contribute significantly to the identification of patients with possible hereditary tumorigenesis. Certain morphological and immunohistochemical features may indicate a genetic background-for example, a lymphocyte-rich, triple-negative phenotype, G3, with medullary features may indicate a BRCA1 mutation, or an invasive lobular carcinoma may indicate a CDH1 mutation. Clinical constellations such as early age of onset, bilateral tumors, associated tumors, or familial clustering are also important indicators.The identification of a germline mutation has far-reaching consequences for the affected individual and the entire family. Intensive follow-up care programs are offered to those affected; risk-reducing surgery may be considered for mutations in certain risk genes. There are also therapeutic implications, such as the use of PARP inhibitors in BRCA1/2-associated HER2-negative breast cancer. Predictive genetic testing may be considered for relatives as well as intensified early detection programs and risk-reducing surgery, if necessary.Close interdisciplinary cooperation is therefore crucial in order to identify patients with possible hereditary tumorigenesis at an early stage and to enable an individualized therapy and follow-up care strategy.