Validation of Breast Cancer Risk Models by Race/Ethnicity, Family History and Molecular Subtypes

SIMPLE SUMMARY: Several statistical models exist to predict a person’s risk of breast cancer. Risk assessment models can guide cancer screening approaches by identifying individuals who would benefit from additional screening. In this study, we compared the performance of four models in predicting the 5-year risk of breast cancer in a cohort of women aged 40–84 years who underwent screening mammography at three large health systems. Models showed comparable discrimination (ability to distinguish between cases and non-cases) and calibration (ability to accurately predict risk) overall, with no difference by race. Model discrimination was poorer for some cancer subtypes, and better for women with high BMI. The combined BRCAPRO+BCRAT model had improved calibration and discrimination among women with a family history of breast cancer. Our results can inform risk-based screening approaches by identifying women at a high risk of breast cancer. ABSTRACT: (1) Background: The purpose of this study is to compare the performance of four breast cancer risk prediction models by race, molecular subtype, family history of breast cancer, age, and BMI. (2) Methods: Using a cohort of women aged 40–84 without prior history of breast cancer who underwent screening mammography from 2006 to 2015, we generated breast cancer risk estimates using the Breast Cancer Risk Assessment tool (BCRAT), BRCAPRO, Breast Cancer Surveillance Consortium (BCSC) and combined BRCAPRO+BCRAT models. Model calibration and discrimination were compared using observed-to-expected ratios (O/E) and the area under the receiver operator curve (AUC) among patients with at least five years of follow-up. (3) Results: We observed comparable discrimination and calibration across models. There was no significant difference in model performance between Black and White women. Model discrimination was poorer for HER2+ and triple-negative subtypes compared with ER/PR+HER2−. The BRCAPRO+BCRAT model displayed improved calibration and discrimination compared to BRCAPRO among women with a family history of breast cancer. Across models, discriminatory accuracy was greater among obese than non-obese women. When defining high risk as a 5-year risk of 1.67% or greater, models demonstrated discordance in 2.9% to 19.7% of patients. (4) Conclusions: Our results can inform the implementation of risk assessment and risk-based screening among women undergoing screening mammography.