In summary, using isogenic cell line models of luminal A breast cancer, we demonstrated that FGFR1 overexpression resulted in palbociclib resistance, which was associated with enhanced ER-RTK crosstalk and attenuated downregulation of G1/S regulators (cyclin D3, pRb-E2F1 axis) and cyclins/CDKs (cyclin B1, cdc2/CDK1, cdc25) that promote mitotic entry. This evidence concerns the gene ESR1 and breast cancer.