In breast cancer, pioneering work in risk prediction, modelling genetic susceptibility based on two genes, BRCA1 and BRCA2, [50] has been expanded to the use of polygenic scores, which have improved predictive ability. In a recent study, a PRS based on 303 genetic variants had an AUC of 0.63, with an odds ratio of 1.61 (95% confidence interval, 1.57–1.65) per unit increase in PRS [3]. Whilst these figures are modest, they translate into a substantial spread of risk in the population: women in the top 1% of PRS have a 4-fold increased risk of developing ER-positive breast cancer and a corresponding 6-fold decreased risk for those in the lowest 1% PRS (both compared to women in the mid-quintile of the PRS distribution). Despite the modest discriminative ability, PRS could be utilised in improving screening programmes, including defining the age at which breast cancer screening should start and the screening interval. In the UK, mammogram screening is offered to women over age 47, when the average 10-year risk of breast cancer is ~ 2.6%. However, Mavaddat et al. [3] show that
