HBOC (Hereditary Breast and Ovarian Cancer), a paradigm shift for counseling and treatment of patients with defects in homologous recombination - an explorative study

Our knowledge about genes, associated with an increased risk of hereditary breast and ovarian cancer, has increased significantly. However, the exact risks associated with germline mutations, in these recently detected genes, are not yet known. This creates a complex situation in communicating genetic test results to persons who have a mutation in these genes. To get more insight into the risks, we will develop a national database in this inter-university project to gather relevant information to better estimate the risks.

All known breast cancer genes play a role in the repair of fractures in DNA via a specific recovery mechanism, homologous recombination (HR). This is an interesting issue as it can be therapeutically intervened by treatment with PARP inhibitors. The purpose of this project is therefore to perform a clinical trial phase 2 with PARP inhibitors in patients with a mutation in a gene involved in HR. Furthermore, we will investigate whether patients with a mutation in an HR gene can be identified by studying the DNA that circulates in plasma from these patients. This would allow patients to benefit from treatment with PARP inhibitors based on a simple blood decrease rather than through a tumor biopsy. Through this interuniversity cooperation we expect to be able to contribute strongly to the clinical utility of genetic tests of breast cancer predisposition genes, both in the context of cancer prevention and therapy.