Consider delaying adding CDK4/6, mTOR, or PIK3CA inhibitors to endocrine therapy, especially in elderly patients with comorbidities, in the following situations:1. Where endocrine-therapy alone is providing effective tumor control2. In first line3. Low disease burden or bone-only diseaseDose reduction of palbociclib does not decrease efficacy. The gene discussed is MTOR; the disease is neoplasm.