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

Mol Oncol. 2012 Aug;6(4):437-44. doi: 10.1016/j.molonc.2012.05.003. Epub 2012 Jun 1.

Abstract

Background: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Breast Neoplasms / blood*
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / metabolism*
  • Clinical Trials, Phase III as Topic
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Humans
  • Lapatinib
  • 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

Substances

  • Quinazolines
  • Lapatinib
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • Paclitaxel