Thank you.
I would like to thank the committee for this opportunity to expose some of our work.
For 21 years I have been the holder of a Canada research chair in cancer genetics. I'm also a fellow of the Royal Society of Canada.
A screening program will be sustainable if it delivers more benefit than harm, demonstrates value for money, is feasible to implement, is accepted by both the users and the providers and ensures equitable accessibility.
Currently, breast screening programs determine eligibility based on age, primarily targeting women aged 50 to 74 years of age with mammograms every two years. However, the risk of developing breast cancer varies a lot among women. There are no national guidelines for screening individuals deemed high risk. Screening protocols vary across jurisdictions, and the definition of high risk of developing breast cancer also varies across Canada.
Typically, women are identified as high risk based on a family history of breast cancer followed by testing for BRCA1 and BRCA2 gene mutations. This identification process is often initiated ad hoc by the affected individual and their care provider rather than through systemic population-based identification strategies. This approach overlooks women without a known family history but with a significant genetic predisposition and women at high risk due to the combination of other risk factors like polygenic risk, lifestyle and hormonal factors and mammographic breast density.
Polygenic risk scores represent the combined effect of multiple genetic variants on cancer risk identified through genome-wide association studies—called the genomic approach—and provide a powerful risk prediction approach with the potential to identify many more individuals at high or low cancer risk than is possible by screening based on age alone. In this regard, comprehensive risk prediction tools, including both genetic and non-genetic risk factors, have shown promise in providing personalized risk prediction and informing cancer-screening strategies.
A risk-stratified program involves assessing the risk of breast cancer for each woman in the population, stratifying the population into several risk groups, assigning individuals to their respective risk groups and tailoring the screening strategy to each risk group. This approach may result in some women starting mammographic screening at a younger age, having different screening intervals or having supplemental screening with another imaging modality such as MRI. Additionally, women deemed to be at the highest risk of breast cancer could be offered prophylactic preventative treatment.
Evidence from simulation studies so far shows that risk-stratified screening allows for better trade-offs between benefits and harms. By focusing more intensive screening efforts on high-risk individuals, it is possible to detect cancers earlier in this group while reducing unnecessary screening of low-risk populations. This targeted approach would potentially lead to earlier detection and improved outcomes and reduce overdiagnosis and overtreatment. Also, these studies have shown that risk-stratified screening programs are more cost-effective than the current age-based screening, allowing more efficient use of resources within health care systems.
For 25 years I've been the principal investigator of an international interdisciplinary team. Our last large-scale project was called “Personalized Risk Assessment for Prevention and Early Detection of Breast Cancer: Integration and Implementation”, which is the first study that will provide real-world evidence on the optimal implementation of approaches within the Canadian health care system. The Perspective I and I study leverages resources available through the existing screening program, including infrastructure, data collection, methods and analytical tools. This will enable seamless integration into the existing health care infrastructure and facilitate adoption into clinical practice.
Our project will inform collection of saliva sample and questionnaire-based risk information at the population level, risk communication preferences, psychological and emotional outcomes following communication of breast cancer risk information, adherence to the risk-based recommendations of screening, outcomes of screening—cancer detection rates, false positive rates, stage of diagnosis—using multifactorial risk levels and also the relative contribution of self-reported risk factors, mammographic density and the polygenic risk score to breast cancer risk level estimates by the comprehensive CanRisk prediction tool.
This assessment is to strike a balance between the accuracy of risk assessment and the practicality of collecting this information at the population level.
Identifying screening protocols will optimize the cost-effectiveness and a benefit-harm balance of a risk-stratified screening program. We're also looking for a strategy to increase the health care organizational readiness to implement a risk-based breast screening program.
So far, we have learned that it's feasible to collect samples and data for risk estimation. More than 4,000 women participated in Ontario and Quebec in this real-world implementation study. Risk-based screening is acceptable to the woman and to the health care provider. Using multifactorial risk levels compared to age, family history or breast density alone may provide more appropriate recommendations by reducing over-screening in those at average risk and increasing screening for those at higher risk.
Thank you for your time.