ESR1 and breast carcinoma: In fact, the identification of cyclins and CDKs was reported as early as the 1970s, and this discovery was recognized by the Nobel in 2001.[5] CDK4/6i targets the CDK-RB1-E2F pathway, which is vital in the progression of the cell cycle and does not function properly in most cancers.[6] In breast cancer (BC), the activation of estrogen receptors (ER) triggers the complexation of CDK4/6 with cyclin D1.