Saadatmand S, et al. - By performing a multicenter, randomized, controlled trial (FaMRIsc), MRI screening was compared with mammography in screening women with familial risk for breast cancer. Eligible participants were those who aged 30-55 years with a cumulative lifetime breast cancer risk of at least 20% due to a familial predisposition, but were BRCA1, BRCA2, and TP53 wild-type. Women who were breastfeeding, pregnant, had a previous breast cancer screen, or had a previous diagnosis of ductal carcinoma in situ, were eligible for participation. Among 1,355 women who provided consent for randomization and 231 who provided consent for registration, 675 were randomized to receive annual MRI and clinical breast examination plus biennial mammography (MRI group) and 680 were allocated to receive annual mammography and clinical breast examination (mammography group). Outcomes revealed that cancer can be detected at an earlier stage using MRI screening vs mammography. A reduction in the use of adjuvant chemotherapy and decrease in breast cancer-related mortality could result from the low number of late-stage cancers identified in incident rounds. The advantages of the MRI screening approach could come with more false-positive results, particularly with high breast density.