Résumé : The present invention relates to methods for determining sensitivity to a cyclin dependent kinase 4 or 6 (CDK4/6) inhibitor in a human subject having breast cancer. The present invention provides a gene expression signature as a companion diagnostic to a CDK4/6 inhibitor that allows determining whether a human subject having breast cancer will benefit from treatment with a CDK4/6 inhibitor or whether the subject has no direct clinical benefit from such treatment or whether the subject will be insensitive to the drug.