Comparison of 5- and 10-year breast cancer risk predictions.

Abstract

10529 Background: Breast cancer risk assessment is valuable in personalizing risk-reduction and screening approaches for the general population. Maximizing the benefits while reducing the harms associated with current breast cancer screening and risk-reduction recommendations should increase the efficacy of these paradigms. Because healthcare providers have limited time with their patients, we developed a risk prediction model, BRISK, which uses the most important clinical risk factors for breast cancer (in an easily collected format), polygenic risk and mammographic density. We previously validated BRISK 5-year risk predictions and found that it performed better than IBISv7 and BCRAT. Methods: The dataset comprised 241,633 women (mean age at baseline assessment = 56.6 years). We included all races/ethnicities available in the UK Biobank. There were 3726 women affected during the first five years of follow-up and 7482 women affected during the full 10 years of follow-up. We compared the performance of the 5-year and 10-year risk predictions by assessing the association with breast cancer using Cox regression to estimate the hazard ratio (HR) per SD of risk, discrimination using calculating Harrell’s C-index and calibration using logistic regression to estimate the slope and the intercept of the logit of the risk predictions. Nelson–Aalen estimates of the hazard function by quintiles of risk and standardized incidence ratios (SIRs) of the number of breast cancer cases expected were used to illustrate performance. Results: The predictive performance of BRISK was consistent for 5-year and 10-year risk predictions. Discrimination was similar, with a Harrell’s C-index of 0.645 (95% CI = 0.636, 0.654) for the 5-year risk and of 0.638 (95% CI = 0.632, 0.645) for the 10-year risk. We used Nelson_Aalen cumulative hazard estimates to compare breast cancer incidence by risk quintile for both 5 and 10-year risk. Both risk scores overestimated risk in the top two deciles with the 5-year expected risks of 2.8% and 5.0% corresponding to observed risks of 2.3% and 3.3%. The 10-year expected risks for the top two deciles were 5.6% and 9.8% while the corresponding observed risks were 4.6% and 6.4%. Finally, we used clinically actionable thresholds to show the standard incidence ratios (SIR) of 1.77 (95% CI = 1.69, 1.85) for women ≥3% 5-year risk and 2.05 (95% CI = 1.93, 2.18) ≥8% 10-year risk. Conclusions: The BRISK 5-year and 10-year risk prediction perform equally well. There is an overestimation of risk for the top decile in both models. This is important to consider in risk-management conversations between clinician and patient. While the observed risk of the top decile remained above the 3% 5-year risk threshold used in the United States, the top decile observed risk dropped below the 8% 10-year risk threshold used in the United Kingdom. Risk scores are not used in isolation, but it may be preferable to err on the side of overestimation rather than underestimation.