Disseminated tumor cells of breast cancer patients: A strong prognostic factor for distant and local relapse
Disseminated tumor cells of breast cancer patients: A strong prognostic factor for distant and local relapse
复制标题
DOI：
10.1158/1078-0432.ccr-07-4749
复制
发表时间：
2008-06-01
影响因子：
11.5
通讯作者：
Pierga, Jean-Yves
中科院分区：
文献类型：
--
作者：
Bidard, Francois-Clement;Vincent-Salomon, Anne;Pierga, Jean-Yves
目的：报道了早期乳腺癌患者骨髓弥散性肿瘤细胞（DTC）的临床意义，但检测方法有待改进。实验设计：从621例I至III期乳腺癌患者的骨髓抽吸中筛选细胞角蛋白阳性（CK+）细胞。CK+细胞只有在具有肿瘤细胞的特定形态特征时才被归类为DTC。中位随访56个月后，患者骨髓状态、临床及病理变量与临床预后相关。结果：DTC和非DTC CK+细胞检出率分别为15%和34%，与临床和病理变量无关。在单因素分析中，DTC检测与较差的远端无转移生存（DMFS, P = 0.0013）和总生存（OS, P = 0.005）相关。此外，DTC检测也与局部无复发生存相关（P = 0.0009）。在多变量分析中，DTC检测是DMFS、局部无复发生存和OS的独立预后因素。DTC检测与激素受体状态无显著交互作用（P = 0.34）。非dtc CK+细胞无临床意义。结论：DTC检测是早期乳腺癌患者DMFS和OS的有力预后指标，可根据形态学标准从无关的非DTC CK+细胞个体化。生物学上，尽管在该系列研究中，全身辅助治疗和局部放疗的比例很高，但DTC检测仍然是远处复发的预后因素，更引人注目的是，局部复发的预后因素，有利于DTC阳性患者对局部或远处扩散癌细胞的治疗产生耐药性。
Purpose: Clinical significance of disseminated tumor cells (DTC) in bone marrow of early breast cancer patients has been reported, but improvements in detection methods are needed.Experimental Design: Bone marrow aspirates from 621 patients with stage I to III breast cancer were screened for cytokeratin-positive (CK+) cells. CK+ cells were categorized into DTC only if they had specific morphologic features of tumor cells. Bone marrow status and clinical and pathologic variables of the patients were correlated with clinical outcome after a median follow-up of 56 months.Results: DTC and non-DTC CK+ cells were detected in 15% and 34% of patients, respectively, with no correlation with clinical and pathologic variables. On univariate analysis, DTC detection was associated with a poorer distant metastasis-free survival (DMFS; P = 0.0013) and overall survival (OS; P = 0.005). Moreover, DTC detection was also associated with local relapse-free survival (P = 0.0009). On multivariate analysis, DTC detection was an independent prognostic factor for DMFS, local relapse-free survival, and OS. There was no significant interaction between DTC detection and hormonal receptors status (P = 0.34). Non-DTC CK+ cells had no clinical significance.Conclusion: DTC detection is a powerful prognostic marker for DMFS and OS in early breast cancer patients and can be individualized from irrelevant non-DTC CK+ cells by morphologic criteria. Biologically, despite high rates of systemic adjuvant therapy and locoregional irradiation in this series, DTC detection remains a prognostic factor of distant and, more strikingly, of local relapse, in favor of resistance to treatment of locally or distant disseminated cancer cells in DTC-positive patients.