SUN-675 Breast Cancer Treatment Causes Diabetes

Introduction: Alpelisib (BYL719) a PI3K p110alpha inhibitor, was recently FDA approved to treat postmenopausal women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, PIK3CA gene mutation positive, advanced or metastatic breast cancer following progression on endocrine-based regimen. A major side effect of this cancer therapy is severe hyperglycemia. Case Report: 78 year old female with prediabetes, presents with 5 days of polyuria, polydipsia, blurred vision, severe fatigue and pre-syncope. Random blood glucose at home was >500mg/dL. She has a history of ER, PR positive and HER2 negative invasive adenocarcinoma of right breast with bone metastases that has progressed on chemotherapy, radiation therapy and hormone therapy. Her PI3KCA gene mutation was positive and she was started on alpelisib a week prior to hospitalization. Physical examination revealed heart rate 98/min, blood pressure 160/74mmHg, BMI 21, dry oral mucosa and reduced skin turgor. Urinalysis showed >1000mg/dL glycosuria. Random plasma glucose was 354mg/dL. Creatinine was 1.07mg/dL (baseline 0.70mg/dL). She was resuscitated with IV saline and started on glimepiride 2mg oral twice daily, glargine 5 units at bedtime with correctional insulin regimen. Despite therapy, plasma glucose remained 180-350mg/dL. Discontinuation of alpelisib, rapidly improved her plasma glucose. Discussion: PI3K (phosphatidylinositol 3 kinase) activation by insulin is a key step in whole body glucose metabolism. PI3K inhibition leads to glycogen breakdown in liver and marked insulin resistance by reduced glucose uptake in skeletal muscle and adipose tissue. Treatment options using oral agents or insulin are limited in these patients. As more patients with cancer are approved for treatment with PI3K inhibitors, clinicians need to be more aware of the mechanism of hyperglycemia to effectively manage it. More evidence based consensus is needed on management of hyperglycemia with PI3K inhibition.