A metabolic phenotyping approach to understanding relationships between metabolic syndrome and breast tumor responses to chemotherapy.

Abstract

10544 Background: Breast cancer is associated with adverse outcomes in patients with the metabolic syndrome phenotype. We previously demonstrated using a metabolic profiling (metabonomics) approach that glucose, lactate and alanine levels were perturbed during chemotherapy and that these effects were associated with weight gain during treatment. To validate these data and study this further, we examined the relationship between serum metabolite levels and the components of metabolic syndrome with treatment outcomes in breast cancer. Methods: A total of 88 women with measurable breast cancer were studied; their serum metabolites as assessed by 1H NMR spectroscopy, blood pressure, lipids, glucose, body mass index and waist circumference were recorded and correlated with treatment response. Results: We identified metabolic syndrome in approximately half of our cohort (42 patients) and observed a significant trend (p=0.03) of increased incidence of metabolic syndrome in partial response (33.3%), stable disease (42.9%) and progressive disease groups (66.1%). Of the components of metabolic syndrome, high blood sugar predicted a poor response (p < 0.001). Logistic regression of metabonomic data demonstrated that high lactate (p=0.03) and low alanine (p=0.01), combined with high glucose (p=0.01) in the same sera, were associated with disease progression. Conclusions: Metabolic syndrome is commonly observed in women with metastatic breast cancer and these patients have poorer outcomes. These data, which support our previous findings suggest that high blood glucose as part of metabolic syndrome is associated with a poor response in breast cancer. They also validate new therapeutic approaches that focus on metabolism.