title: Serum metabolomic profiles evaluated after surgery may identify patients with oestrogen receptor negative early breast cancer at increased risk of disease recurrence. Results from a retrospective study.
abstract: OBJECTIVE
  Metabolomics is a global study of metabolites in biological samples. In this study we explored whether serum metabolomic spectra could distinguish between early and metastatic breast cancer patients and predict disease relapse.
  
  
  METHODS
  Serum samples were analysed from women with metastatic (n = 95) and predominantly oestrogen receptor (ER) negative early stage (n = 80) breast cancer using high resolution nuclear magnetic resonance spectroscopy. Multivariate statistics and a Random Forest classifier were used to create a prognostic model for disease relapse in early patients.
  
  
  RESULTS
  In the early breast cancer training set (n = 40), metabolomics correctly distinguished between early and metastatic disease in 83.7% of cases. A prognostic risk model predicted relapse with 90% sensitivity (95% CI 74.9-94.8%), 67% specificity (95% CI 63.0-73.4%) and 73% predictive accuracy (95% CI 70.6-74.8%). These results were reproduced in an independent early breast cancer set (n = 40), with 82% sensitivity, 72% specificity and 75% predictive accuracy. Disease relapse was associated with significantly lower levels of histidine (p = 0.0003) and higher levels of glucose (p = 0.01), and lipids (p = 0.0003), compared with patients with no relapse.
  
  
  CONCLUSIONS
  The performance of a serum metabolomic prognostic model for disease relapse in individuals with ER-negative early stage breast cancer is promising. A confirmation study is ongoing to better define the potential of metabolomics as a host and tumour-derived prognostic tool.
authors.affiliation: Magnetic Resonance Center (CERM), University of Florence, Via L. Sacconi 6, 50019 Sesto Fiorentino, Italy; FiorGen Foundation, Via L. Sacconi 6, 50019 Sesto Fiorentino, Italy. Electronic address: tenori@cerm.unifi.it.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Tenori
authors.affiliation: 'Sandro Pitigliani' Medical Oncology Department, Hospital of Prato, Via Suor Niccolina 20, Istituto Toscano Tumori, 59100 Prato, Italy. Electronic address: catherine.oakman@mh.org.au.
authors.forename: Catherine
authors.initials: C
authors.lastname: Oakman
authors.affiliation: Breast Cancer Medicine Service, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA. Electronic address: morrisp1@mskcc.org.
authors.forename: Patrick G
authors.initials: PG
authors.lastname: Morris
authors.affiliation: Magnetic Resonance Center (CERM), University of Florence, Via L. Sacconi 6, 50019 Sesto Fiorentino, Italy; FiorGen Foundation, Via L. Sacconi 6, 50019 Sesto Fiorentino, Italy. Electronic address: gralka@cerm.unifi.it.
authors.forename: Ewa
authors.initials: E
authors.lastname: Gralka
authors.affiliation: 'Sandro Pitigliani' Medical Oncology Department, Hospital of Prato, Via Suor Niccolina 20, Istituto Toscano Tumori, 59100 Prato, Italy. Electronic address: nhturner@usl4.toscana.it.
authors.forename: Natalie
authors.initials: N
authors.lastname: Turner
authors.affiliation: 'Sandro Pitigliani' Medical Oncology Department, Hospital of Prato, Via Suor Niccolina 20, Istituto Toscano Tumori, 59100 Prato, Italy. Electronic address: scappadona@usl4.toscana.it.
authors.forename: Silvia
authors.initials: S
authors.lastname: Cappadona
authors.affiliation: Breast Cancer Medicine Service, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA. Electronic address: fornierm@mskcc.org.
authors.forename: Monica
authors.initials: M
authors.lastname: Fornier
authors.affiliation: Breast Cancer Medicine Service, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA. Electronic address: hudisc@mskcc.org.
authors.forename: Cliff
authors.initials: C
authors.lastname: Hudis
authors.affiliation: Breast Cancer Medicine Service, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA. Electronic address: nortonl@mskcc.org.
authors.forename: Larry
authors.initials: L
authors.lastname: Norton
authors.affiliation: Magnetic Resonance Center (CERM), University of Florence, Via L. Sacconi 6, 50019 Sesto Fiorentino, Italy; Department of Chemistry, University of Florence, Via della Lastruccia 3, 50019 Sesto Fiorentino, Italy. Electronic address: luchinat@cerm.unifi.it.
authors.forename: Claudio
authors.initials: C
authors.lastname: Luchinat
authors.affiliation: 'Sandro Pitigliani' Medical Oncology Department, Hospital of Prato, Via Suor Niccolina 20, Istituto Toscano Tumori, 59100 Prato, Italy. Electronic address: adileo@usl4.toscana.it.
authors.forename: Angelo
authors.initials: A
authors.lastname: Di Leo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000097:blood* / Q000175:diagnosis* / Q000601:surgery*; D005260:Female; D006801:Humans; D055442:Metabolome; D055432:Metabolomics; D008875:Middle Aged; D008954:Models, Biological; D009364:Neoplasm Recurrence, Local; D011237:Predictive Value of Tests; D011379:Prognosis; D011960:Receptors, Estrogen; D012189:Retrospective Studies
chemical_list: D011960:Receptors, Estrogen
keywords: Biomarker; Breast cancer; Metabolites; Metabolomics; Micrometastases; Nuclear magnetic resonance spectroscopy