Genetics

Abstract: About 10–30% of breast cancers are estimated to be explained by known (mostly modifiable) lifestyle and environmental factors; this is population dependent. Another 20–30% of breast cancers can be explained by germline genetics. For women with pathogenic BRCA1 and BRCA2 mutations, the risk of developing breast cancer is estimated to be between 27% and 80% by age 70 years, compared to a 4–12% lifetime risk for the general female population worldwide. Pathogenic mutations in BRCA1 increase risk for ovarian cancer as well as for a range of other tumours. After genetic testing, the gene mutation status can be used for cancer risk prediction in affected and healthy individuals. But even when no pathogenic variant in an established breast cancer gene is detected, persons can still be at increased risk of breast cancer due to a mutation in a gene that was not tested, or more likely, a probably polygenic, heritable component that is not (yet) known. With all the technical advances that have been made in sequencing in recent years, gene panel testing has been developed, enabling testing for mutations, simultaneously, in a set of multiple genes. Currently, genetic testing and breast cancer risk prediction is mainly done for high-risk individuals and families in the clinical genetic setting. However, the infrastructures for implementation of population-based genetic testing are under development.