Breast cancer is a malignant tumour that starts in the cells of the breast. It is a group of cancer cells that can grow into (invade) surrounding tissues or spread (metastasize) to distant areas of the body. The disease occurs almost entirely in women, but men can develop it, too. Worldwide, breast cancer is the most frequently occurring malignant tumour diagnosed and the principal cause of death in women.
The most common hereditary cause of breast cancer is hereditary breast and ovarian cancer syndrome (Hereditary Breast and Ovarian Cancer Syndrome or HBOC), which is caused by a germline mutation in either the BRCA1 or BRCA2 gene. HBOC is characterized by an increased risk for male and female breast cancer, ovarian cancer (includes fallopian tube and primary peritoneal cancers), and to a lesser extent other cancers such as prostate cancer, pancreatic cancer, and melanoma. Germline pathogenic variants in BRCA1 and BRCA2 genes are inherited in an autosomal dominant manner.
In the 1990s, it was demonstrated for the first time that the DNA repair genes BRCA1 and BRCA2 are directly associated with HBOC. Currently, it is estimated that approximately 5–10% of all patients with breast cancer and approximately 20% of all patients with ovarian cancer exhibit a monogenic predisposition to breast and ovarian cancer.
In the past few years more than 25 genes have been associated with familial breast and/or ovarian cancer and still more expected to emerge. Most of the identified HBOC genes encodes for proteins involved in genome maintenance pathways connected with BRCA1 and BRCA2. For example we can found involved genes such as: ATM, BARD1, CHEK2, MLH1, PALB2, PTEN, TP53, FANCC and FANCM.
The risk of breast and ovarian cancer may differ between the individual genes and variants and from family to family. For nearly all of the emerging HBOC genes, it is currently not possible to provide individual accurate risk estimation. However, we can consider that people carrying pathogenic mutations in BRCA1 and BRCA2 genes have a significantly elevated risk of breast and ovarian cancer.