METABOLIC MONITORING DURING PI3K/AKT PATHWAY INHIBITION IN HR -POSITIVE/HER2 - NEGATIVE ADVANCED BREAST CANCER: FROM BASELINE RISK ASSESSMENT TO EARLY INTERVENTION

Targeted inhibition of the PI3K/AKT pathway has expanded biomarker-guided treatment options for patients with hormone receptor - positive/human epidermal growth factor receptor 2- negative (HR -positive/HER2- negative) advanced breast cancer. However, disruption of physiological insulin signaling is a clinically relevant on -target effect of several agents in this therapeutic class and may result in treatment -associated hyperglycemia. This narrative review summarizes current approaches to baseline risk assessment, glucose monitoring, and early intervention during treatment with alpelisib, inavolisib, and capivasertib. Pretreatment evaluation should include fasting glucose, glycated hemoglobin (HbA1c), body mass index, a history of diabetes or prediabetes , concomitant medications, and other factors associated with impaired glucose tolerance. Monitoring should be agent- specific because the timing of glycemic abnormalities and recommended monitoring schedules differ substantially between therapies. Particular attention is required during the first weeks of treatment, when dysglycemia may develop rapidly. Early identification of glucose abnormalities enables timely lifestyle intervention, initiation or intensification of antihyperglycemic therapy, and appropriate modification of anticancer treatment when required. A proactive multidisciplinary strategy integrating baseline risk stratification, early glucose monitoring, and prompt intervention may reduce the risk of severe metabolic complications and support continuity of anticancer therapy. Metabolic monitoring should therefore be incorporated into routine management of patients receiving PI3K/AKT pathway- directed treatment rather than initiated only after clinically significant hyperglycemia has developed.