Abstract
BACKGROUND: Incorporation of polygenic risk scores and mammographic density into models to predict breast cancer incidence can increase discriminatory accuracy (area under the receiver operating characteristic curve [AUC]) from 0.6 for models based only on epidemiologic factors to 0.7. It is timely to assess what impact these improvements will have on individual counseling and on public health prevention and screening strategies, and to determine what further improvements are needed. METHODS: We studied various clinical and public health applications using a log-normal distribution of risk. RESULTS: Provided they are well calibrated, even risk models with AUCs of 0.6 to 0.7 provide useful perspective for individual counseling and for weighing the harms and benefits of preventive interventions in the clinic. At the population level, they are helpful for designing preventive intervention trials, for assessing reductions in absolute risk from reducing exposure to modifiable risk factors, and for resource allocation (although a higher AUC would be desirable for risk-based allocation). Other public health applications require higher AUCs that can only be achieved with risk predictors 1.6 to 8.8 times as strong as all those yet discovered combined. Such applications are preventing an appreciable proportion of population disease when employing a high-risk prevention strategy and deciding who should be screened for subclinical disease. CONCLUSIONS: Current and foreseeable risk models are useful for counseling and some prevention activities, but given the daunting challenge of achieving, for example, an AUC of 0.8, considerable effort should be put into finding effective preventive interventions and screening strategies with fewer adverse effects.