Lactate and glycine-potential MR biomarkers of prognosis in estrogen receptor-positive breast cancers

• Published in: NMR in biomedicine 2012-11, Vol.25 (11), p.1271-1279
• Main Authors: Giskeødegård, Guro F., Lundgren, Steinar, Sitter, Beathe, Fjøsne, Hans E., Postma, Geert, Buydens, Lutgarde M. C., Gribbestad, Ingrid S., Bathen, Tone F.
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor - metabolism; Biopsy; Breast Neoplasms - diagnosis; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cohort Studies; Discriminant Analysis; estrogen receptor; Female; Glycine - metabolism; HR MAS; Humans; Kaplan-Meier Estimate; Lactic Acid - metabolism; Least-Squares Analysis; Magnetic Resonance Spectroscopy; metabolomics; Middle Aged; MRS; multivariate analysis; NMR; PCA; PLS-DA; Principal Component Analysis; Prognosis; Receptors, Estrogen - metabolism; ROC Curve
• ISSN: 0952-3480; 1099-1492
• DOI: 10.1002/nbm.2798

Breast cancer is a heterogeneous disease with a variable prognosis. Clinical factors provide some information about the prognosis of patients with breast cancer; however, there is a need for additional information to stratify patients for improved and more individualized treatment. The aim of this study was to examine the relationship between the metabolite profiles of breast cancer tissue and 5‐year survival. Biopsies from breast cancer patients (n = 98) were excised during surgery and analyzed by high‐resolution magic angle spinning MRS. The data were analyzed by multivariate principal component analysis and partial least‐squares discriminant analysis, and the findings of important metabolites were confirmed by spectral integration of the metabolite peaks. Predictions of 5‐year survival using metabolite profiles were compared with predictions using clinical parameters. Based on the metabolite profiles, patients with estrogen receptor (ER)‐positive breast cancer (n = 71) were separated into two groups with significantly different survival rates (p = 0.024). Higher levels of glycine and lactate were found to be associated with lower survival rates by both multivariate analyses and spectral integration, and are suggested as biomarkers for breast cancer prognosis. Similar metabolic differences were not observed for ER‐negative patients, where survivors could not be separated from nonsurvivors. Predictions of 5‐year survival of ER‐positive patients using metabolite profiles gave better and more robust results than those using traditional clinical parameters. The results imply that the metabolic state of a tumor may provide additional information concerning breast cancer prognosis. Further studies should be conducted in order to evaluate the role of MR metabolomics as an additional clinical tool for determining the prognosis of patients with breast cancer. Copyright © 2012 John Wiley & Sons, Ltd. In this study, we have revealed differences in the metabolite profiles of breast cancer biopsies (n = 98) from 5‐year survivors and nonsurvivors using high‐resolution magic angle spinning MRS. The metabolites lactate and glycine were more strongly expressed in nonsurvivors and are potential biomarkers for breast cancer prognosis. MR metabolomics may serve as a tool for the evaluation of prognosis in patients with breast cancer