Impact of Diabetes and Hyperglycemia on Survival in Advanced Breast Cancer Patients

Abstract

Purpose. We examined the impact of diabetes and hyperglycemia on cancer-specific survival of patients with metastatic or recurrent breast cancer (BC). Methods. We performed a retrospective analysis of 265 patients with advanced BC receiving palliative chemotherapy. BC-specific mortality was compared for diabetic and nondiabetic patients as well as for patients that presented hyperglycemia during treatment. Results. No difference was observed between the diabetic and nondiabetic patients in terms of overall survival (OS). A difference in OS was observed between nondiabetic patients and diabetic patients who had hyperglycemia. The OS was greater in diabetic patients with proper metabolic control than diabetic patients with hyperglycemia. The risk of death was higher in patients with mean glucose levels >130 mg/dL during treatment. Several factors were associated with poor OS: tumor stage, hormone-receptor-negative tumors, HER2 negative disease, multiple metastatic sites, presence of visceral metastases, and mean glucose >130 mg/dL. Conclusion. Elevated glucose levels are associated with a poor outcome in diabetic and nondiabetic patients in contrast to patients with normoglycemic levels, conferring an elevated risk of death. According to these results, clinicians should monitor glucose levels during treatment for advanced breast cancer disease and take action to maintain normal glucose levels.

Potential Roles of GLUT12 for Glucose Sensing and Cellular Migration in MCF-7 Human Breast Cancer Cells Under High Glucose Conditions

“…Moreover, clinical epidemiological studies have shown that breast tumor progression and response to therapy differ between women with and without diabetes (4, 7, 10). The presence of a high glucose level, corresponding to hyperglycemia in vivo, has been reported to modulate breast cancer cell functions including survival, growth, and proliferation, suggesting the glucose level as being critical for breast cancer progression in patients with diabetes (11)(12)(13)(14)(15)(16)(17)(18)(19). Our previous studies also demonstrated that the migratory ability of MCF-7 human breast cancer cells, which is linked to invasion and metastasis, was strongly dependent on glucose concentration (13,14).…”

Cancer-drug induced insulin resistance: Innocent bystander or unusual suspect

“…Insulin resistance prior to cancer treatment was identified as an independent negative factor influencing overall survival, progression-free survival and development of treatment resistance in various cancer types [28,[77][78][79][80][81][82]. A retrospective study in 130 lymphoma patients identified high fasting blood glucose levels at diagnosis as a predictor of decreased overall-and progression-free survival [77].…”

“…Furthermore, a study in 1734 prostate cancer patients with localised disease treated with radical prostatectomy or radiation therapy identified glucose levels at time of diagnosis as an independent predictor of recurrence [78]. Moreover, high glucose levels in non-diabetic as well as diabetic patients with metastatic or recurrent breast cancer treated with palliative chemotherapy decreased overall survival [79]. An association between high pre-cancer treatment fasting blood glucose levels and the development of treatment resistance was observed in a population of 202 breast cancer patients treated with trastuzumab [80].…”

Clinical potential of the mTOR effectors S6K1, S6K2 and 4EBP1 in breast cancer

“…globulins. Also hyperglycaemia has been associated with increased risk of developing cancer, among others breast cancer [200], as well as a poor breast cancer outcome [201].…”