PROJECT SUMMARY – Project 2 Digital breast tomosynthesis use has rapidly increased for breast cancer screening, outpacing evidence of effectiveness in community settings for women overall and for specific populations. Emerging evidence suggests tomosynthesis may lower recall rates while simultaneously improving cancer detection. However, critical questions remain: whether early reports of improved screening outcomes remain beyond initial screening rounds and are sustainable in community settings; whether tomosynthesis outcomes vary based on women’s characteristics; whether tomosynthesis is equal to or outperforms supplemental MRI screening; and whether additional cancers detected are likely to lead to reduced morbidity and mortality from breast cancer. With the rapid shift to tomosynthesis as the dominant screening modality, a thorough understanding of its effectiveness in community settings across subgroups of women is needed. In our current P01, using the rich data resource of the Breast Cancer Surveillance Consortium (BCSC), we have demonstrated the importance of woman-level characteristics on digital mammography screening outcomes. Given the quick uptake of tomosynthesis in the BCSC, it is now possible to examine outcomes of tomosynthesis screening in relation to woman-level factors and to quantify the benefit-harm balance. Our overall project objective is to identify the most effective screening strategies that incorporate new screening technologies in community practice based on women's risk factors. We hypothesize that tomosynthesis will perform better than digital mammography for some, but not all, women and that there are some women who may benefit from multi-modal screening. We will also evaluate whether tomosynthesis can reduce the need for supplemental magnetic resonance imaging (MRI) in women at high risk of a missed cancer on digital mammography. We specifically aim to: Aim 1) determine the benefits and harms of screening tomosynthesis compared to digital mammography based on women's characteristics Aim 2) determine the observed benefits and harms of multi-modality screening with supplemental MRI versus tomosynthesis alone; and Aim 3) evaluate the long- term benefits and harms from multi-modality screening with supplemental MRI versus tomosynthesis screening alone across risk groups through simulation modeling (in conjunction with the Comparative Effectiveness Core). This project will fill critical knowledge gaps regarding the effectiveness of tomosynthesis and multi-modality screening, which we believe will have direct translation into actionable screening guidelines