Modulation of the Estrogen/erbB2 Receptors Cross-talk by CDK4/6 Inhibition Triggers Sustained Senescence in Estrogen Receptor- and ErbB2-positive Breast Cancer.

Resistance associated with the combination of drugs targeting ER and HER2 can be bypassed by cotargeting Rb, enhancing transition from quiescence to sustained senescence. MTORC1 pathway activation is a potential mechanism of escape and RTKs functional activation may be an alternative pathway for survival also in ER+/HER2low tumor. PFHPert combination is an effective chemotherapy-free regimen for ER+/HER2+ breast cancer, and the mechanistic elucidation of sensitivity/resistance patterns may provide insights for further treatment refinement.