Because genomic instability is a hallmark of malignant transformation [35], especially among BRCA1 familial cancers [36] and aggressive sporadic breast cancers [37], we hypothesized that Brca1 mutation would accelerate the tumor development we observed following dual inactivation of pRbf and p53. Our results show that concomitant inactivation of all three tumor suppressor pathways in mammary epithelium has an additive effect on tumor latency and predisposes highly penetrant, malignant carcinomas. This evidence concerns the gene TP53 and breast cancer.