Department of Circulation and Medical Imaging, Norwegian University of Science and Technology (NTNU), 7489 Trondheim, Norway.
BMC Cancer. 2012 Jan 25;12:39. doi: 10.1186/1471-2407-12-39.
Today's clinical diagnostic tools are insufficient for giving accurate prognosis to breast cancer patients. The aim of our study was to examine the tumor metabolic changes in patients with locally advanced breast cancer caused by neoadjuvant chemotherapy (NAC), relating these changes to clinical treatment response and long-term survival.
Patients (n = 89) participating in a randomized open-label multicenter study were allocated to receive either NAC as epirubicin or paclitaxel monotherapy. Biopsies were excised pre- and post-treatment, and analyzed by high resolution magic angle spinning magnetic resonance spectroscopy (HR MAS MRS). The metabolite profiles were examined by paired and unpaired multivariate methods and findings of important metabolites were confirmed by spectral integration of the metabolite peaks.
All patients had a significant metabolic response to NAC, and pre- and post-treatment spectra could be discriminated with 87.9%/68.9% classification accuracy by paired/unpaired partial least squares discriminant analysis (PLS-DA) (p < 0.001). Similar metabolic responses were observed for the two chemotherapeutic agents. The metabolic responses were related to patient outcome. Non-survivors (< 5 years) had increased tumor levels of lactate (p = 0.004) after treatment, while survivors (≥ 5 years) experienced a decrease in the levels of glycine (p = 0.047) and choline-containing compounds (p ≤ 0.013) and an increase in glucose (p = 0.002) levels. The metabolic responses were not related to clinical treatment response.
The differences in tumor metabolic response to NAC were associated with breast cancer survival, but not to clinical response. Monitoring metabolic responses to NAC by HR MAS MRS may provide information about tumor biology related to individual prognosis.
目前的临床诊断工具不足以准确预测乳腺癌患者的预后。我们的研究旨在检查新辅助化疗（NAC）引起的局部晚期乳腺癌患者的肿瘤代谢变化，并将这些变化与临床治疗反应和长期生存联系起来。
参与随机开放标签多中心研究的患者（n=89）被分配接受表阿霉素或紫杉醇单药 NAC。治疗前和治疗后切除活检，并通过高分辨率魔角旋转磁共振波谱（HRMAS MRS）分析。通过配对和非配对多变量方法检查代谢物谱，并通过代谢物峰的谱积分确认重要代谢物的发现。
所有患者对 NAC 均有明显的代谢反应，且配对/非配对偏最小二乘判别分析（PLS-DA）可将治疗前后的光谱以 87.9%/68.9%的分类准确率区分（p<0.001）。两种化疗药物的代谢反应相似。代谢反应与患者预后相关。未存活者（<5 年）治疗后肿瘤中乳酸水平升高（p=0.004），而存活者（≥5 年）中甘氨酸（p=0.047）和胆碱化合物（p≤0.013）水平降低，葡萄糖水平升高（p=0.002）。代谢反应与临床治疗反应无关。
NAC 引起的肿瘤代谢反应的差异与乳腺癌的生存相关，但与临床反应无关。通过 HRMAS MRS 监测 NAC 的代谢反应可能提供与个体预后相关的肿瘤生物学信息。
