title: Lactate and glycine-potential MR biomarkers of prognosis in estrogen receptor-positive breast cancers.
abstract: 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.
authors.affiliation: Department of Circulation and Medical Imaging, Norwegian University of Science and Technology (NTNU), Trondheim, Norway. guro.giskeodegard@ntnu.no
authors.forename: Guro F
authors.initials: GF
authors.lastname: Giskeødegård
authors.forename: Steinar
authors.initials: S
authors.lastname: Lundgren
authors.forename: Beathe
authors.initials: B
authors.lastname: Sitter
authors.forename: Hans E
authors.initials: HE
authors.lastname: Fjøsne
authors.forename: Geert
authors.initials: G
authors.lastname: Postma
authors.forename: Lutgarde M C
authors.initials: LM
authors.lastname: Buydens
authors.forename: Ingrid S
authors.initials: IS
authors.lastname: Gribbestad
authors.forename: Tone F
authors.initials: TF
authors.lastname: Bathen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000378:metabolism* / Q000473:pathology; D015331:Cohort Studies; D016002:Discriminant Analysis; D005260:Female; D005998:Glycine / Q000378:metabolism*; D006801:Humans; D053208:Kaplan-Meier Estimate; D019344:Lactic Acid / Q000378:metabolism*; D016018:Least-Squares Analysis; D009682:Magnetic Resonance Spectroscopy; D008875:Middle Aged; D025341:Principal Component Analysis; D011379:Prognosis; D012372:ROC Curve; D011960:Receptors, Estrogen / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D011960:Receptors, Estrogen; D019344:Lactic Acid; D005998:Glycine