A long-term image-derived AI-based risk model for primary prevention of breast cancer in individuals at high risk

Image-derived artificial intelligence (AI) risk models have shown promise in short-term risk assessment for improving breast cancer (BC) screening. No image-derived long-term AI risk model for primary prevention has been developed and externally validated. Individuals aged 31 to 94 years were recruited between 2010 and 2020 in two population-based case cohorts (Olmsted County, Minnesota, US, and KARMA, Sweden) and one hospital-based case-control study (EMBED, Atlanta, US). Median follow-up in the case cohorts was 10 years, with BCs diagnosed through June 2022. Additional validation was performed in EMBED with 3-year follow-up. An AI risk model was developed in Sweden, and we report independent validation in Olmsted/KARMA/EMBED. Absolute 10-year risks were estimated at study entry. Time-dependent discriminatory performance [AUC(t)] and expected-to-observed events (E/O) were estimated. Comparisons were performed with clinical risk tools and the image-based Mirai tool. Across Olmsted/KARMA, 8696 individuals (mean age, 54.4±10.6) and 1633 individuals with incident BC (mean age, 57.0±10.6) were included. Average 10-year risks were 3.83 and 3.14%, and E/O ratios were 0.99 and 0.99. Ten-year AUC(t) for invasive BCs were 0.72 in Olmsted and 0.72 in KARMA. Similar discriminatory results were observed in EMBED. Our AI risk tool performed significantly better than Mirai in Olmsted/KARMA/EMBED. In KARMA, in the top 10% of high-risk individuals, the AI risk tool predicted 33% of BCs compared with 23%/20%/24% predicted by Tyrer-Cuzick-v8/BCSC-v3/Mirai (all P < 0.01). The 10-year image-derived AI risk model showed significantly higher performance than clinical risk models and Mirai in diverse populations, supporting its clinical potential for primary prevention.