As early as 2026, a sample of saliva and blood could help better assess the risk of developing breast cancer to enable personalized clinical care. "This is truly a major shift in practice. It's something that's very exciting and encouraging," enthuses Mathias Cavaillé, a clinical physician and teacher at the Faculty of Medicine and researcher at the CHU de Québec - Université Laval Research Centre.
He is leading a research project to integrate a new tool into the clinical staff's arsenal: the polygenic risk score. Combined with non-genetic risk factors, such as age, breast density, body mass index, or lifestyle, it will allow for a more precise assessment of risk level.
Mammography is currently the most effective examination for breast cancer screening.
Image Wikimedia A tool to refine screening
The polygenic risk score is particularly interesting for women considered at moderate genetic or familial risk of breast cancer. Their lifetime risk is estimated at 20%, which is twice that of the general population. In reality, one in two women would have a higher or lower risk level. "Out of 100 patients considered at moderate risk, there are 25 who are at low risk and 25 who are at high risk, comparable to that induced by BRCA1 and 2 mutations," illustrates Mathias Cavaillé.
The "historical" approach would have been to manage all of them in the same way, either through annual or biennial mammography screening starting at age 40. With personalized risk assessment, women with risk comparable to the general population could start screening later, at age 50. Women at high risk, on the other hand, could benefit from intensive follow-up, with annual screening by mammography and magnetic resonance imaging from age 30 or 35, or even preventive surgery.
When genetics meets the clinic
Certain genetic mutations in breast cancer predisposition genes like BRCA1 and 2 are known to induce high or moderate risk. But other more common genetic variations in the population also influence the probability of developing the disease.
It is these latter variations that are considered in the polygenic risk score, which counts 313 of them. Individually, these mutations are associated with a low risk of cancer, but when combined, they can significantly increase it.
As a clinician, the majority of these patients are women with a family risk of breast cancer for whom no mutations are found in the predisposition genes, which complicated management.
The research project is funded by Génome Québec, the Fondation cancer du sein de Québec, and the Fondation du CHU de Québec.