In preclinical models of breast cancer, disruption of the TP53 pathway and/or constitutive activation of HER2, FAK or KRAS produce DCIS, but further inhibition of pRb signalling and/or activation of the phosphatidylinositol 3′-kinase pathway appear necessary to promote malignant progression (Lightfoot et al, 2004; Golubovskaya et al, 2009; Wu et al, 2009). The gene discussed is RB1; the disease is ductal breast carcinoma in situ.