- 作者：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
- 关键词：Metabolomics ; Breast cancer ; Metastatic ; HER2 positive ; Prediction
- 刊名：Molecular Oncology
- 出版年：2012
- 出版时间：August, 2012
- 年：2012
- 卷：6
- 期：4
- 页码：437-444
- 全文大小：314 K
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.