Magnetic Resonance Center (CERM), University of Florence, Via L. Sacconi 6, 50019 Sesto Fiorentino, Italy.
Mol Oncol. 2012 Aug;6(4):437-44. doi: 10.1016/j.molonc.2012.05.003. Epub 2012 Jun 1.
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.
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.
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%).
In metastatic breast cancer, metabolomics may play a role in sub selecting patients with HER2 positive disease with greater sensitivity to paclitaxel plus lapatinib.
代谢组学是对代谢物和小分子进行全面研究的一个新兴扩展领域。在这项初步研究中，代谢组学已被应用于转移性乳腺癌女性的血清样本中，以探索治疗结果和对治疗的反应。
本国际临床试验中，579 例转移性乳腺癌患者被随机分配至紫杉醇联合靶向抗 HER2 治疗（拉帕替尼）或安慰剂组，研究人员获得了这些患者的治疗前和治疗过程中（序贯）的血清样本。采用 600MHz 核磁共振波谱技术获取血清代谢组学图谱。对图谱与无进展生存期、总生存期和治疗毒性进行了比较。
评估了超过 500 例患者的治疗前和治疗过程中的血清样本。在未进行生物学选择的整个试验人群中，代谢组学图谱与结局或毒性均无相关性。在接受紫杉醇联合拉帕替尼治疗的 HER2 阳性疾病患者亚组中，数据集上三分之一和下三分之一患者的代谢组学图谱在无进展生存期（N = 22，预测准确性 = 89.6%）和总生存期（N = 16，预测准确性 = 78.0%）方面存在显著差异。
在转移性乳腺癌中，代谢组学可能在选择对紫杉醇联合拉帕替尼更敏感的 HER2 阳性疾病患者方面发挥作用。
