Uncertainty quantification in breast cancer risk prediction models using self-reported family health history

Introduction. Family health history (FHx) is an important factor in breast and ovarian cancer risk assessment. As such, multiple risk prediction models rely strongly on FHx data when identifying a patient’s risk. These models were developed using verified information and when translated into a clinical setting assume that a patient’s FHx is accurate and complete. However, FHx information collected in a typical clinical setting is known to be imprecise and it is not well understood how this uncertainty may affect predictions in clinical settings. Methods. Using Monte Carlo simulations and existing measurements of uncertainty of self-reported FHx, we show how uncertainty in FHx information can alter risk classification when used in typical clinical settings. Results. We found that various models ranged from 52% to 64% for correct tier-level classification of pedigrees under a set of contrived uncertain conditions, but that significant misclassification are not negligible. Conclusions. Our work implies that (i) uncertainty quantification needs to be considered when transferring tools from a controlled research environment to a more uncertain environment (i.e, a health clinic) and (ii) better FHx collection methods are needed to reduce uncertainty in breast cancer risk prediction in clinical settings.