Müller Volkmar, Riethdorf Sabine, Rack Brigitte, Janni Wolfgang, Fasching Peter A, Solomayer Erich, Aktas Bahriye, Kasimir-Bauer Sabine, Pantel Klaus, Fehm Tanja
Breast Cancer Res. 2012 Aug 15;14(4):R118. doi: 10.1186/bcr3243.
There is a multitude of assays for the detection of circulating tumor cells (CTCs) but a very limited number of studies comparing the clinical relevance of results obtained with different test methods. The DETECT trial for metastatic breast cancer patients was designed to directly compare the prognostic impact of two commercially available CTC assays that are prominent representatives of immunocytochemical and RT-PCR based technologies.
In total, 254 metastatic breast cancer patients were enrolled in this prospective multicenter trial. CTCs were assessed using both the AdnaTest Breast Cancer and the CellSearch system according to the manufacturers' instructions.
With the CellSearch system, 116 of 221 (50%) evaluable patients were CTC-positive based on a cut-off level at 5 or more CTCs. The median overall survival (OS) was 18.1 months in CTC-positive patients. (95%-CI: 15.1-22.1 months) compared to 27 months in CTC-negative patients (23.5-30.7 months; p<0.001). This prognostic impact for OS was also significant in the subgroups of patients with triple negative, HER2-positive and hormone receptor-positive/HER2-negative primary tumors. The progression free survival (PFS) was not correlated with CTC status in our cohort receiving different types and lines of systemic treatment (p = 0.197). In multivariate analysis, the presence of CTCs was an independent predictor for OS (HR: 2.7, 95%-CI: 1.6-4.2). When the AdnaTest Breast was performed, 88 of 221 (40%) patients were CTC-positive. CTC-positivity assessed by the AdnaTest Breast had no association with PFS or OS.
The prognostic relevance of CTC detection in metastatic breast cancer patients depends on the test method. The present results indicate that the CellSearch system is superior to the AdnaTest Breast Cancer in predicting clinical outcome in advanced breast cancer.
Current Controlled Trials Registry number ISRCTN59722891.
检测循环肿瘤细胞(CTC)的方法众多,但比较不同检测方法所得结果临床相关性的研究却非常有限。转移性乳腺癌患者的DETECT试验旨在直接比较两种市售CTC检测方法的预后影响,这两种方法分别是免疫细胞化学和基于逆转录聚合酶链反应(RT-PCR)技术的突出代表。
共有254例转移性乳腺癌患者纳入了这项前瞻性多中心试验。根据制造商的说明,使用AdnaTest乳腺癌检测法和CellSearch系统对CTC进行评估。
使用CellSearch系统,在221例可评估患者中,有116例(50%)基于5个或更多CTC的临界值水平为CTC阳性。CTC阳性患者的中位总生存期(OS)为18.1个月(95%置信区间:15.1 - 22.1个月),而CTC阴性患者为27个月(23.5 - 30.7个月;p<0.001)。这种对OS的预后影响在三阴性、HER2阳性和激素受体阳性/HER2阴性原发性肿瘤患者亚组中也很显著。在接受不同类型和疗程全身治疗的队列中,无进展生存期(PFS)与CTC状态无关(p = 0.197)。在多变量分析中,CTC的存在是OS的独立预测因素(风险比:2.7,95%置信区间:1.6 - 4.2)。当进行AdnaTest乳腺癌检测时,221例患者中有88例(40%)为CTC阳性。AdnaTest乳腺癌检测评估的CTC阳性与PFS或OS均无关联。
转移性乳腺癌患者中CTC检测的预后相关性取决于检测方法。目前的结果表明,在预测晚期乳腺癌的临床结局方面,CellSearch系统优于AdnaTest乳腺癌检测法。
当前受控试验注册编号ISRCTN59722891。