循环肿瘤细胞可预测中高危早期乳腺癌患者的生存情况。
Circulating tumor cells predict survival in early average-to-high risk breast cancer patients.
机构信息
Affiliations of authors: Department of Gynecology and Obstetrics, Ludwig-Maximilians-University Munich, Munich, Germany (BR, JJ, UA, KF); Department of Gynecology and Obstetrics, Clinical Center Traunstein, Traunstein, Germany (CS); Department of Gynecology and Obstetrics, Heinrich-Heine-University Duesseldorf, Duesseldorf, Germany (PH, TF); Augsburg, Germany (TZ); Braunschweig, Germany (RL); Frankfurt, Germany (HT); National Center for Tumor Diseases, University Hospital, Heidelberg, Germany (AS); Charité University Hospital Campus Virchow, Berlin, Germany (WL); Department of Obstetrics and Gynecology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-Nuremberg, Erlangen, Germany (PAF, MWB); Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (KP); Department of Gynecology and Obstetrics, University Hospital Ulm, Ulm, Germany (TWPF, WJ).
出版信息
J Natl Cancer Inst. 2014 May 15;106(5):dju066. doi: 10.1093/jnci/dju066.
BACKGROUND
Circulating tumor cells (CTCs) have been shown to predict reduced survival outcomes in metastatic breast cancer.
METHODS
CTCs were analyzed in 2026 patients with early breast cancer before adjuvant chemotherapy and in 1492 patients after chemotherapy using the CellSearch System. After immuno-magnetic enrichment for cells expressing the epithelial-cell adhesion molecule, CTCs were defined as nucleated cells expressing cytokeratin and lacking CD45. The patients were followed for a median of 35 months (range = 0-54). Kaplan-Meier analyses and the log-rank test were used for survival analyses. All statistical tests were two-sided.
RESULTS
Before chemotherapy, CTCs were detected in 21.5% of patients (n = 435 of 2026), with 19.6% (n = 136 of 692) of node-negative and 22.4% (n = 299 of 1334) of node-positive patients showing CTCs (P < .001). No association was found with tumor size, grading, or hormone receptor status. After chemotherapy, 22.1% of patients (n = 330 of 1493) were CTC positive. The presence of CTCs was associated with poor disease-free survival (DFS; P < .0001), distant DFS (P < .001), breast cancer-specific survival (P = .008), and overall survival (OS; P = .0002). CTCs were confirmed as independent prognostic markers in multivariable analysis for DFS (hazard ratio [HR] = 2.11; 95% confidence interval [CI] = 1.49 to 2.99; P < .0001) and OS (HR = 2.18; 95% CI = 1.32 to 3.59; P = .002). The prognosis was worst in patients with at least five CTCs per 30 mL blood (DFS: HR = 4.51, 95% CI = 2.59 to 7.86; OS: HR = 3.60, 95% CI = 1.56 to 8.45). The presence of persisting CTCs after chemotherapy showed a negative influence on DFS (HR = 1.12; 95% CI = 1.02 to 1.25; P = .02) and on OS (HR = 1.16; 95% CI = 0.99 to 1.37; P = .06) CONCLUSIONS: These results suggest the independent prognostic relevance of CTCs both before and after adjuvant chemotherapy in a large prospective trial of patients with primary breast cancer.
背景
已有研究表明，循环肿瘤细胞（CTC）可预测转移性乳腺癌患者的生存预后降低。
方法
采用 CellSearch 系统，对 2026 例接受辅助化疗前的早期乳腺癌患者和 1492 例化疗后的患者进行 CTC 分析。免疫磁珠富集表达上皮细胞黏附分子的细胞后，将 CTC 定义为表达细胞角蛋白且缺乏 CD45 的有核细胞。中位随访时间为 35 个月（范围 0-54 个月）。采用 Kaplan-Meier 分析和对数秩检验进行生存分析。所有统计检验均为双侧检验。
结果
化疗前，435 例（2026 例中的 21.5%）患者存在 CTC，其中 136 例（692 例中的 19.6%）淋巴结阴性患者和 299 例（1334 例中的 22.4%）淋巴结阳性患者存在 CTC（P<.001）。肿瘤大小、分级或激素受体状态与 CTC 均无相关性。化疗后，330 例（1493 例中的 22.1%）患者 CTC 阳性。存在 CTC 与无病生存（DFS；P<.0001）、远处 DFS（P<.001）、乳腺癌特异性生存（P=.008）和总生存（OS；P=.0002）不良相关。多变量分析显示，CTC 是 DFS（风险比[HR] = 2.11；95%置信区间[CI] = 1.49 至 2.99；P<.0001）和 OS（HR = 2.18；95% CI = 1.32 至 3.59；P =.002）的独立预后标志物。每 30 mL 血液中至少有 5 个 CTC 的患者预后最差（DFS：HR = 4.51，95% CI = 2.59 至 7.86；OS：HR = 3.60，95% CI = 1.56 至 8.45）。化疗后持续存在 CTC 对 DFS（HR = 1.12；95% CI = 1.02 至 1.25；P =.02）和 OS（HR = 1.16；95% CI = 0.99 至 1.37；P =.06）有负面影响。
结论
这些结果表明，在一项针对原发性乳腺癌患者的大型前瞻性试验中，CTC 在辅助化疗前后均具有独立的预后相关性。
Zotero 插件