Mankoff David A, Dunnwald Lisa K, Gralow Julie R, Ellis Georgiana K, Charlop Aaron, Lawton Thomas J, Schubert Erin K, Tseng Jeffrey, Livingston Robert B
Division of Nuclear Medicine, Box 346113, University of Washington, 1959 E Pacific Street, Seattle, WA 98195, USA.
J Nucl Med. 2002 Apr;43(4):500-9.
Locally advanced breast cancer (LABC) is commonly treated with neoadjuvant chemotherapy followed by definitive surgery. The factors influencing the response of LABC to presurgical chemotherapy are incompletely understood. To characterize in vivo tumor biology in patients with LABC, we measured pretherapy blood flow and glucose metabolism in LABC, compared measurements with clinical and pathologic parameters, and examined blood flow and response to subsequent neoadjuvant chemotherapy.
Thirty-seven patients with newly diagnosed LABC underwent (18)F-FDG and (15)O-water PET imaging. Thirty-one of these patients underwent neoadjuvant chemotherapy, and response was evaluated by serial measurements of tumor size and pathologic examination after definitive surgery after chemotherapy. Tumor metabolism was estimated from graphic analysis of dynamic (18)F-FDG studies and was expressed as the metabolic rate of (18)F-FDG (MRFDG). Blood flow was estimated from dynamic images after bolus (15)O-water injection using a 1-compartment model. Tumor blood flow and metabolism were compared with clinical and pathologic parameters and with response to chemotherapy.
Both blood flow and metabolism were significantly higher in tumor than in normal breast. Tumor blood flow and metabolism were correlated but highly variable. There were weak associations of metabolism with patient age and tumor grade and of blood flow with estrogen receptor status. There was a statistically significant trend for patients with a high MRFDG to have a poorer response to therapy (P = 0.001). Response was not significantly correlated with any other parameters. A low ratio of MRFDG to blood flow was the best predictor of macroscopic complete response (CR) (P = 0.02 vs. non-CR). Preliminary analysis of patient follow-up showed the ratio of MRFDG to blood flow to also be predictive of disease-free survival.
Despite uniformly large tumor size, blood flow and metabolism in LABC are highly variable. High glucose metabolism predicts a poor response to neoadjuvant chemotherapy, and low MRFDG relative to blood flow is a predictor of CR. Further work is needed to elucidate the biologic mechanisms underlying these findings.
局部晚期乳腺癌（LABC）通常采用新辅助化疗后进行确定性手术治疗。LABC对术前化疗反应的影响因素尚未完全明确。为了描述LABC患者的体内肿瘤生物学特征，我们测量了LABC患者治疗前的血流和葡萄糖代谢，将测量结果与临床和病理参数进行比较，并研究了血流与后续新辅助化疗反应的关系。
37例新诊断的LABC患者接受了（18）F-FDG和（15）O-水PET成像。其中31例患者接受了新辅助化疗，化疗后通过对肿瘤大小的系列测量和确定性手术后的病理检查评估反应。肿瘤代谢通过动态（18）F-FDG研究的图形分析进行估计，并表示为（18）F-FDG的代谢率（MRFDG）。血流通过使用单室模型在注射团注（15）O-水后的动态图像进行估计。将肿瘤血流和代谢与临床和病理参数以及化疗反应进行比较。
肿瘤中的血流和代谢均显著高于正常乳腺。肿瘤血流和代谢相关但高度可变。代谢与患者年龄和肿瘤分级以及血流与雌激素受体状态之间存在弱关联。MRFDG高的患者对治疗反应较差有统计学意义的趋势（P = 0.001）。反应与任何其他参数均无显著相关性。MRFDG与血流的低比值是宏观完全缓解（CR）的最佳预测指标（与非CR相比，P = 0.02）。对患者随访的初步分析表明，MRFDG与血流的比值也可预测无病生存期。
尽管LABC的肿瘤大小均一较大，但其血流和代谢高度可变。高葡萄糖代谢预示着对新辅助化疗反应较差，相对于血流的低MRFDG是CR的预测指标。需要进一步的工作来阐明这些发现背后的生物学机制。
