ESR1 and neoplasm: However, the predictive value of Rb remains uncertain, as tumor analyses performed on two large randomized phase 3 clinical trials (PALOMA-2 and 3, examining palbociclib in combination with AI or fulvestrant versus AI or fulvestrant alone, respectively, in patients with ER+/HER2−ABC) failed to show a statistically significant correlation between Rb (at mRNA or protein level) and resistance to CDK4/6i [18,19].