Impact of adding breast density to breast cancer risk models: A systematic review

Purpose: Assessment of a woman's risk of breast cancer is essential when moving towards personalized screening. Breast density is a well-known risk factor and has the potential to improve accuracy of risk prediction models. In this study we reviewed the impact on model performance of adding breast density to clinical breast cancer risk prediction models. Methods: We conducted a systematic review using a pre-specified search strategy for PubMed, EMBASE, Web of Science, and Cochrane Library from January 2007 until November 2019. Studies were screened using the Covidence software. Eligible studies developed or modified existing breast cancer risk prediction models applicable to the general population of women by adding breast density to the model. Improvement in discriminatory accuracy was measured as an increase in the Area Under the Curve or concordance statistics. Results: Eleven eligible studies were identified by the search and one by reference check. Four studies modified the Gail model, four modified the Tyrer-Cuzick model, and five studies developed new models. Several methods were used to measure breast density, including visual, semi- and fully automated methods. Eleven studies reported discriminatory accuracy and one study reported calibration. Seven studies found a statistically significantly increased discriminatory accuracy when including density in the model. The increase in AUC ranged 0.03 to 0.14. Four studies did not report on statistical significance, but reported an increased AUC ranging from 0.01 to 0.06. Conclusion: Including mammographic breast density has the potential to improve breast cancer risk prediction models. However, all models demonstrated limited discrimination accuracy.