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.

Developing and validating COVID-19 adverse outcome risk prediction models from a bi-national European cohort of 5594 patients.

Patients with severe COVID-19 have overwhelmed healthcare systems worldwide. We hypothesized that machine learning (ML) models could be used to predict risks at different stages of management and thereby provide insights into drivers and prognostic markers of disease progression and death. From a cohort of approx. 2.6 million citizens in Denmark, SARS-CoV-2 PCR tests were performed on subjects suspected for COVID-19 disease; 3944 cases had at least one positive test and were subjected to further analysis. SARS-CoV-2 positive cases from the United Kingdom Biobank was used for external validation. The ML models predicted the risk of death (Receiver Operation Characteristics-Area Under the Curve, ROC-AUC) of 0.906 at diagnosis, 0.818, at hospital admission and 0.721 at Intensive Care Unit (ICU) admission. Similar metrics were achieved for predicted risks of hospital and ICU admission and use of mechanical ventilation. Common risk factors, included age, body mass index and hypertension, although the top risk features shifted towards markers of shock and organ dysfunction in ICU patients. The external validation indicated fair predictive performance for mortality prediction, but suboptimal performance for predicting ICU admission. ML may be used to identify drivers of progression to more severe disease and for prognostication patients in patients with COVID-19. We provide access to an online risk calculator based on these findings.