BRCA1 and breast cancer: Loss of p53 or its downstream target, p21, in vivo as well as knockdown of p16 or its downstream target, Rb, in vitro partially rescues the premature senescence of Brca1-deficient cells [24–28, 30], suggesting that disruption of the p53 and p16-Rb pathway are required to overcome Brca1-deficiency induced senescence and induce breast cancers.