RB1 and breast cancer: In addition, ER signaling pathway is able to activate CCND1 gene promoter.4,5 Cyclin D1 can also stimulate ER transcriptional activity in a CDK 4-independent manner.6 On the other hand, cyclin E expression is reported as low in ER-positive BC7 and RB mutations are rarely found,8 reflecting the dependence of ER-positive BC cells on cyclin D1 to start G1-to-S phase transition.