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

• Published in: Annals of oncology Vol. 23; no. 4; pp. 860 - 866
• Main Authors: Stebbing, J., Sharma, A., North, B., Athersuch, T.J., Zebrowski, A., Pchejetski, D., Coombes, R.C., Nicholson, J.K., Keun, H.C.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.04.2012; Oxford University Press
• Subjects: Adult; Aged; Aged, 80 and over; Antineoplastic agents; Biological and medical sciences; biomarkers; Blood Glucose; Blood Pressure; breast cancer; Breast Neoplasms - blood; Breast Neoplasms - complications; Breast Neoplasms - drug therapy; Carcinoma, Ductal, Breast - blood; Carcinoma, Ductal, Breast - complications; Carcinoma, Ductal, Breast - drug therapy; diabetes; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; Gynecology. Andrology. Obstetrics; Humans; Logistic Models; Mammary gland diseases; Medical sciences; Metabolic diseases; metabolic syndrome; Metabolic Syndrome - blood; Metabolic Syndrome - complications; metabolomics; Middle Aged; Miscellaneous; Multivariate Analysis; Other metabolic disorders; Pharmacology. Drug treatments; Phenotype; Postmenopause; Treatment Outcome; Triglycerides - blood; Tumors; metabolic syndrome; breast cancer; metabolomics; diabetes; biomarkers; Endocrinopathy; Metabolomics; Breast disease; Diabetes mellitus; Breast tumor; Biological marker; Metabolic diseases; Cardiovascular disease; Breast cancer; Malignant tumor; Metabolism; Metabolic syndrome; Mammary gland diseases; Chemotherapy; Treatment; Metabonomics; Pharmacokinetics; Cancer
• ISSN: 0923-7534; 1569-8041
• DOI: 10.1093/annonc/mdr347

Breast cancer is associated with adverse outcomes in patients with the metabolic syndrome phenotype. To study this further, we examined the relationship between serum metabolite levels and the components of metabolic syndrome with treatment outcomes in breast cancer. A total of 88 women with measurable breast cancer were studied; their serum metabolites as assessed by 1H nuclear magnetic resonance spectroscopy, blood pressure, lipids, glucose, body mass index and waist circumference were recorded and correlated with treatment response. 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%). 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) were associated with disease progression. Metabolic syndrome is commonly observed in 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.