Journal
JOURNAL OF PERSONALIZED MEDICINE
Volume 11, Issue 9, Pages -Publisher
MDPI
DOI: 10.3390/jpm11090916
Keywords
absolute risk; remaining lifetime risk; risk threshold; risk-stratified screening; misclassification
Funding
- Government of Canada through Genome Canada [13529]
- Canadian Institutes of Health Research [155865]
- Ministere de l'Economie et de l'Innovation du Quebec through Genome Quebec
- Quebec Breast Cancer Foundation
- CHU de Quebec Foundation
- Ontario Research Fund
- Cancer Research UK [C12292/A20861, PPRPGM-Nov20\100002]
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In risk-stratified cancer screening, incorporating multiple risk factors into risk assessment and using age-dependent absolute risk thresholds are crucial to avoid missing high-risk individuals and ensure accurate risk stratification. Using age-independent risk thresholds may lead to misclassification of individuals with equivalent risk levels and offer them different screening plans. Therefore, age-dependent risk thresholds should be considered for accurate risk assessment and stratification.
In risk-stratified cancer screening, multiple risk factors are incorporated into the risk assessment. An individual's estimated absolute cancer risk is linked to risk categories with tailored screening recommendations for each risk category. Absolute risk, expressed as either remaining lifetime risk or shorter-term (five- or ten-year) risk, is estimated from the age at assessment. These risk estimates vary by age; however, some clinical guidelines (e.g., enhanced breast cancer surveillance guidelines) and ongoing personalised breast screening trials, stratify women based on absolute risk thresholds that do not vary by age. We examine an alternative approach in which the risk thresholds used for risk stratification vary by age and consider the implications of using age-independent risk thresholds on risk stratification. We demonstrate that using an age-independent remaining lifetime risk threshold approach could identify high-risk younger women but would miss high-risk older women, whereas an age-independent 5-year or 10-year absolute risk threshold could miss high-risk younger women and classify lower-risk older women as high risk. With risk misclassification, women with an equivalent risk level would be offered a different screening plan. To mitigate these problems, age-dependent absolute risk thresholds should be used to inform risk stratification.
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