Development and Validation of Dynamic 5-Year Breast Cancer Risk Model Using Repeated Mammograms

Abstract

PURPOSE Current image-based long-term risk prediction models do not fully use previous screening mammogram images. Dynamic prediction models have not been investigated for use in routine care. METHODS We analyzed a prospective WashU clinic-based cohort of 10,099 cancer-free women at entry (between November 3, 2008 and February 2012). Follow-up through 2020 identified 478 pathology-confirmed breast cancers (BCs). The cohort included 27% Black women. An external validation cohort (Emory) included 18,360 women screened from 2013, followed through 2020. This included 42% Black women and 332 pathology-confirmed BC excluding those diagnosed within 6 months of screening. We trained a dynamic model using repeated screening mammograms at WashU to predict 5-year risk. This opportunistic screening service presented a range of mammogram images for each woman. We applied the model to the external validation data to evaluate discrimination performance (AUC) and calibrated to US SEER. RESULTS Using 3 years of previous mammogram images available at the current screening visit, we obtained a 5-year AUC of 0.80 (95% CI, 0.78 to 0.83) in the external validation. This represents a significant improvement over the current visit mammogram AUC 0.74 (95% CI, 0.71 to 0.77; P < .01) in the same women. When calibrated, a risk ratio of 21.1 was observed comparing high (>4%) to very low (<0.3%) 5-year risk. The dynamic model classified 16% of the cohort as high risk among whom 61% of all BCs were diagnosed. The dynamic model performed comparably in Black and White women. CONCLUSION Adding previous screening mammogram images improves 5-year BC risk prediction beyond static models. It can identify women at high risk who might benefit from supplemental screening or risk-reduction strategies.