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.
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Authors | Leonardo Tenori, Catherine Oakman, Wederson M Claudino, Patrizia Bernini, Silvia Cappadona, Stefano Nepi, Laura Biganzoli, Michael C Arbushites, Claudio Luchinat, Ivano Bertini, Angelo Di Leo |
Journal | Molecular oncology
(Mol Oncol)
Vol. 6
Issue 4
Pg. 437-44
(Aug 2012)
ISSN: 1878-0261 [Electronic] United States |
PMID | 22687601
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 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
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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
- 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
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