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Exploration of serum metabolomic profiles and outcomes in women with metastatic breast cancer: a pilot study.

AbstractBACKGROUND:
Metabolomics, a global study of metabolites and small molecules, is a novel expanding field. In this pilot study, metabolomics has been applied to serum samples from women with metastatic breast cancer to explore outcomes and response to treatment.
PATIENTS AND METHODS:
Pre-treatment and serial on-treatment serum samples were available from an international clinical trial in which 579 women with metastatic breast cancer were randomized to paclitaxel plus either a targeted anti-HER2 treatment (lapatinib) or placebo. Serum metabolomic profiles were obtained using 600 MHz nuclear magnetic resonance spectroscopy. Profiles were compared with time to progression, overall survival and treatment toxicity.
RESULTS:
Pre- and on-treatment serum samples were assessed for over 500 patients. Unbiased metabolomic profiles in the biologically unselected overall trial population did not correlate with outcome or toxicity. In a subgroup of patients with HER2-positive disease treated with paclitaxel plus lapatinib, metabolomic profiles from patients in the upper and lower thirds of the dataset showed significant differences for time to progression (N = 22, predictive accuracy = 89.6%) and overall survival (N = 16, predictive accuracy = 78.0%).
CONCLUSIONS:
In metastatic breast cancer, metabolomics may play a role in sub selecting patients with HER2 positive disease with greater sensitivity to paclitaxel plus lapatinib.
AuthorsLeonardo Tenori, Catherine Oakman, Wederson M Claudino, Patrizia Bernini, Silvia Cappadona, Stefano Nepi, Laura Biganzoli, Michael C Arbushites, Claudio Luchinat, Ivano Bertini, Angelo Di Leo
JournalMolecular oncology (Mol Oncol) Vol. 6 Issue 4 Pg. 437-44 (Aug 2012) ISSN: 1878-0261 [Electronic] Netherlands
PMID22687601 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
Chemical References
  • Quinazolines
  • lapatinib
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • Paclitaxel
Topics
  • Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
  • Breast Neoplasms (blood, drug therapy, metabolism)
  • Clinical Trials, Phase III as Topic
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Humans
  • Metabolome
  • Metabolomics
  • Neoplasm Metastasis
  • Paclitaxel (therapeutic use)
  • Pilot Projects
  • Quinazolines (therapeutic use)
  • Randomized Controlled Trials as Topic
  • Receptor, ErbB-2 (metabolism)
  • Survival Analysis
  • Time Factors
  • Treatment Outcome

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