‘Genetic variants could help determine whether breast cancer is hereditary’
We already know a lot about genetics and the risk of breast cancer. But much still needs to be done in breast cancer genetics to improve the prognosis and make sure women at high risk aren’t missed. This is what Professor by Special Appointment Marjanka Schmidt will say in her inaugural lecture on 4 March 2022.
Schmidt advocates collecting more data on genetics and the risk of breast cancer and to apply this knowledge to clinical practice. ‘You still see women being diagnosed with breast cancer and only finding out afterwards that they carry a BRCA1 or BRCA2 mutation. Then we’re already too late. We also don’t know enough about which genetic factors determine which women develop an aggressive form of breast cancer or run the risk of a second breast cancer,’ she explains. Schmidt is a group leader at the Netherlands Cancer Institute, the research institute at the Antoni van Leeuwenhoek hospital, and was appointed Professor by Special Appointment in Genetic Epidemiology of Cancer, especially breast cancer, at Leiden University in 2019.
Risk score
Alongside abnormalities in high-risk genes such as BRCA1 and BRCA2, there are more subtle genetic variants that can contribute to the risk of breast cancer. ‘You can see these variants as markers for breast cancer: they are not directly present in a breast cancer gene, but do have an effect on breast cancer risk. You can add them together to arrive at a total risk score,’ says Schmidt. All these variants add weight to the weighing scales of breast cancer risk. At the Clinical Genetics department in the LUMC, experiments have already been conducted in a research setting with testing women for 313 of these genetic variants. ‘We are investigating whether such a polygenic risk score can help us classify women into risk groups. That could be useful if the risk score has consequences for choices in clinical practice, such as extra checks or another form of screening.’
Future
There is enough to do in the near future for genetic breast cancer epidemiologists, says Schmidt. ‘For me, the glass is always half full. We already know much more than we did in 1994 when the first breast cancer gene was discovered, yet too little about which genes are important in the development of aggressive breast tumours or a second breast cancer in the same patient. A greater understanding of the prognosis for an individual patient is increasingly important for treatment decisions.’