Dipartimento Medicina Sperimentale, Sapienza Università di Roma, Viale Regina Elena 324, Roma, Italy.
Int J Cancer. 2010 May 15;126(10):2437-47. doi: 10.1002/ijc.24953.
The prognostic value associated with the detection of circulating tumor cells (CTCs) in metastatic breast cancer by the CellSearch technology raise additional issues regarding the biological value of this information. We postulated that a drug-resistance profile of CTCs may predict response to chemotherapy in cancer patients and therefore could be used for patient selection. One hundred 5 patients with diagnosis of carcinoma were enrolled in a prospective trial. CTCs were isolated from peripheral blood, and positive samples were evaluated for the expression of a panel of genes involved in anticancer drugs resistance. The drug-resistance profile was correlated with disease-free survival (DFS; patients in adjuvant setting) and time to progression (TTP; metastatic patients) in a 24-months follow-up. Objective response correlation was a secondary end point. Fifty-one percent of patients were found positive for CTCs while all blood samples from healthy donors were negative. The drug-resistance profile correlates with DFS and TTP (p < 0.001 in both). Sensitivity of the test: able to predict treatment response in 98% of patients. Specificity of the test: 100%; no sample from healthy subject was positive for the presence of CTCs. Positive and negative predictive values were found to be 96.5 and 100%, respectively. We identified a drug-resistance profile of CTCs, which is predictive of response to chemotherapy, independent of tumor type and stage of disease. This approach may represent a first step toward the individualization of chemotherapy in cancer patients.
CellSearch 技术检测转移性乳腺癌循环肿瘤细胞（CTC）的预后价值引发了关于该信息生物学价值的额外问题。我们假设 CTC 的耐药谱可能预测癌症患者对化疗的反应，因此可用于患者选择。100 名被诊断患有癌的患者入组了一项前瞻性试验。从外周血中分离 CTC，阳性样本评估一组参与抗癌药物耐药的基因的表达。在 24 个月的随访中，耐药谱与无病生存期（DFS；辅助治疗患者）和进展时间（TTP；转移性患者）相关。客观缓解相关性是次要终点。51%的患者 CTC 阳性，而所有健康供者的血液样本均为阴性。耐药谱与 DFS 和 TTP 相关（两者均 p < 0.001）。该检测的灵敏度：能够预测 98%患者的治疗反应。该检测的特异性：100%；健康受试者的样本均未检测到 CTC 的存在。阳性预测值和阴性预测值分别为 96.5%和 100%。我们鉴定了一种 CTC 的耐药谱，它可以预测化疗反应，与肿瘤类型和疾病分期无关。这种方法可能是实现癌症患者化疗个体化的第一步。
