The parental tumour, which was isolated from a patient previously treated with endocrine therapy harbouring an ESR1Y537S, TP53 mutation and loss of genes encoding p16INK4A, p15INK4B and p14ARF, was shown to be initially sensitive to palbociclib treatment suggesting that these genetic alterations do not impact on response to CDK4/6 perturbation and that long-term exposure led to the expansion of the pre-existing RB-null sub-population. The gene discussed is CDKN2A; the disease is neoplasm.