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乳腺癌患者循环肿瘤细胞的检测:预后预测作用

Detection of circulating tumor cells in breast cancer patients: prognostic predictive role.

作者信息

Turker Ibrahim, Uyeturk Ummugul, Sonmez Ozlem Uysal, Oksuzoglu Berna, Helvaci Kaan, Arslan Ulku Yalcintas, Budakoglu Burcin, Alkis Necati, Aksoy Sercan, Zengin Nurullah

机构信息

Medical Oncology Department, Ankara Oncology Training and Research Hospital, Ankara, Turkey.

出版信息

Asian Pac J Cancer Prev. 2013;14(3):1601-7. doi: 10.7314/apjcp.2013.14.3.1601.

Abstract

A determination of circulating tumor cell (CTC) effectiveness for prediction of progression-free survival (PFS) and overall survival (OS) was conducted as an adjunct to standard treatment of care in breast cancer management. Between November 2008 and March 2009, 22 metastatic and 12 early stage breast carcinoma patients, admitted to Ankara Oncology Training and Research Hospital, were included in this prospective trial. Patients' characteristics, treatment schedules and survival data were evaluated. CTC was detected twice by CellSearch method before and 9-12 weeks after the initiation of chemotherapy. A cut-off value equal or greater than 5 cells per 7.5 ml blood sample was considered positive. All patients were female. Median ages were 48.0 (range: 29-65) and 52.5 (range: 35-66) in early stage and metastatic subgroups, respectively. CTC was positive in 3 (13.6%) patients before chemotherapy and 6 (27.3%) patients during chemotherapy in the metastatic subgroup whereas positive in only one patient in the early stage subgroup before and during chemotherapy. The median follow-up was 22.0 (range: 21-23) and 19.0 (range: 5-23) months in the early stage and metastatic groups, respectively. In the metastatic group, both median PFS and OS were significantly shorter in any time CTC positive patients compared to CTC negative patients (PFS: 4.0 vs 14.0 months, Log-Rank p=0.013; and OS: 8.0 months vs. 20.5 months, Log-Rank p<0.001). OS was affected from multiple visceral metastatic sites (p=0.055) and higher grade (p=0.044) besides CTC positivity (log rank p<0.001). Radiological response of chemotherapy was also correlated with better survival (p<0.001). As a result, CTC positivity was confirmed as a prospective marker even in a small patient population, in this single center study. Measurement of CTC by CellSearch method in metastatic breast carcinoma cases may allow indications of early risk of relapse or death with even as few as two measurements during a chemotherapy program, but this finding should be confirmed with prospective trials in larger study populations.

摘要

作为乳腺癌管理标准治疗的辅助手段,开展了一项关于循环肿瘤细胞(CTC)预测无进展生存期(PFS)和总生存期(OS)有效性的研究。2008年11月至2009年3月期间,安卡拉肿瘤培训与研究医院收治的22例转移性乳腺癌患者和12例早期乳腺癌患者被纳入这项前瞻性试验。对患者的特征、治疗方案和生存数据进行了评估。在化疗开始前和化疗开始后9 - 12周,采用CellSearch方法对CTC进行了两次检测。每7.5毫升血样中5个及以上细胞的临界值被视为阳性。所有患者均为女性。早期和转移性亚组的中位年龄分别为48.0岁(范围:29 - 65岁)和52.5岁(范围:35 - 66岁)。在转移性亚组中,化疗前3例(13.6%)患者CTC呈阳性,化疗期间6例(27.3%)患者CTC呈阳性;而在早期亚组中,化疗前和化疗期间只有1例患者CTC呈阳性。早期和转移组的中位随访时间分别为22.0个月(范围:21 - 23个月)和19.0个月(范围:5 - 23个月)。在转移组中,任何时间CTC呈阳性的患者与CTC阴性的患者相比,中位PFS和OS均显著缩短(PFS:4.0个月对14.0个月,对数秩检验p = 0.013;OS:8.0个月对20.5个月,对数秩检验p < 0.001)。除了CTC阳性外,OS还受多个内脏转移部位(p = 0.055)和更高分级(p = 0.044)的影响(对数秩检验p < 0.001)。化疗的放射学反应也与更好的生存相关(p < 0.001)。因此,在这项单中心研究中,即使在患者数量较少的情况下,CTC阳性也被确认为一个前瞻性标志物。在转移性乳腺癌病例中,通过CellSearch方法检测CTC,即使在化疗方案期间仅进行两次检测,也可能提示早期复发或死亡风险,但这一发现应在更大研究人群的前瞻性试验中得到证实。

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