Riethdorf Sabine, Pantel Klaus
Institute of Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Pathobiology. 2008;75(2):140-8. doi: 10.1159/000123852. Epub 2008 Jun 10.
Despite the progress resulting from early detection and improved adjuvant therapy, the prognosis of breast cancer patients is still limited by the occurrence of distant metastases largely due to clinically occult micrometastases that remain undetected at primary diagnosis even by high-resolution imaging approaches. Recent research efforts have concentrated on the identification of additional parameters allowing individual risk assessment and stratification of patients for targeted therapies, since traditional prognostic factors are not sufficient to predict metastatic relapse and treatment decisions are still mainly based on statistical risk parameters. Highly sensitive and specific immunocytochemical and molecular assays now enable the detection and characterization of disseminated and circulating tumor cells (DTCs and CTCs, respectively) at the single cell level in bone marrow (BM) and peripheral blood, providing insights into the first crucial steps of the metastatic cascade. However, because of the still high variability of results in DTC/CTC detection, the necessity of standardized approaches will be discussed. A large number of studies showed that the presence of DTCs in BM has prognostic impact for primary breast cancer patients. DTCs are likely to escape from chemotherapy by maintaining a dormant nonproliferating state. There is also evidence for a stem cell-like phenotype of DTCs, probably contributing to the opportunity to escape from dormancy control and to start expansion to manifest metastases. Blood would also be an ideal source for the detection and monitoring of CTCs because of an easy noninvasive sampling procedure enabling repeated analyses. While prognostic significance of CTCs could be reliably demonstrated for metastatic breast cancer, studies to analyze the impact of CTCs in primary breast cancer patients and the potential to replace or supplement BM analysis are still ongoing. Furthermore, molecular characterization of CTCs might contribute to improving targeted and more individualized cancer therapies.
尽管早期检测和辅助治疗的进步带来了积极效果，但乳腺癌患者的预后仍受到远处转移的限制，这主要是由于临床上隐匿的微转移灶，即使采用高分辨率成像方法，在初次诊断时仍无法检测到。由于传统的预后因素不足以预测转移性复发，且治疗决策仍主要基于统计风险参数，近期的研究工作集中在识别额外的参数，以便对患者进行个体风险评估和分层，从而实施靶向治疗。高灵敏度和特异性的免疫细胞化学及分子检测方法，现在能够在单细胞水平检测和表征骨髓（BM）和外周血中的播散性肿瘤细胞和循环肿瘤细胞（分别为DTCs和CTCs），为转移级联反应的首个关键步骤提供了深入了解。然而，由于DTC/CTC检测结果的变异性仍然很高，将讨论标准化方法的必要性。大量研究表明，BM中存在DTCs对原发性乳腺癌患者具有预后影响。DTCs可能通过维持休眠的非增殖状态来逃避化疗。也有证据表明DTCs具有干细胞样表型，这可能有助于它们逃离休眠控制并开始增殖以形成转移灶。由于血液采样简便、无创，能够进行重复分析，因此血液也是检测和监测CTCs的理想来源。虽然CTCs对转移性乳腺癌的预后意义已得到可靠证实，但分析CTCs对原发性乳腺癌患者的影响以及替代或补充BM分析的潜力的研究仍在进行中。此外，CTCs的分子表征可能有助于改进靶向性更强、更个性化的癌症治疗。
