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

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.

Copyright © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Figures

Figure 1

Time to progression. HER2 positive patients treated with paclitaxel‐lapatinib (n = 22). Orthogonal partial least squares score plot: red circles: short TTP; green triangles: long TTP.

Figure 2

Overall survival. HER2 positive patients treated with paclitaxel‐lapatinib (n = 16). Orthogonal partial least squares score plot: red circles: short OS; green triangles: long OS.