In a patient with de novo stage IV breast carcinoma harboring an RB1 Q395* (nonsense) mutation, would treatment with a CDK4/6 inhibitor be appropriate, or should it be avoided due to likely resistance?  

Thank you for bringing up this question. As I outlined below, it makes sense based on the evidence available that CDK4/6 inhibitors are less effective or ineffective in patients with tumors harboring Rb LOF mutations. There is, however, little guidance from clinical trials or guidelines to lead us t...