Since Rb loss is not common in ER+ breast cancer, and hence may not be sufficient to predict patient response to palbociclib39, we also interrogated the effect of cyclin E. We have previously shown that post-translational modification (cleavage) of full-length cyclin E generates an oncogenic form termed low-molecular-weight isoforms of cyclin E (LMWE)40, which is uniquely expressed in tumours, hyperphosphorylates Rb, mediates resistance to letrozole and is a strong prognostic indicator in breast cancer41, 42, 43, 44. This evidence concerns the gene RB1 and breast cancer.