To date, the role of cyclin E1 as a marker of de novo resistance has been demonstrated in other tumor types such as ovarian and gastric cancer37,38 but only suggested in BC.33,39 Our data suggest that both CCNE1 and the CCNE1/RB1 ratio, which evaluates both CCNE1 and RB1, might serve as “pan-cancer” markers of de novo resistance to palbociclib and that the CCNE1/RB1 ratio might serve as better marker compared to the single biomarkers CCNE1 and RB1 used separately, both in BC and in other cancer types. Here, RB1 is linked to breast cancer.