Wong Nan Soon, Kahn Harriette J, Zhang Liying, Oldfield Stephanie, Yang Lu-Ying, Marks Alexander, Trudeau Maureen E
Department of Medical Oncology, Sunnybrook and Women's College Health Sciences Centre, Toronto, Ontario, Canada.
Breast Cancer Res Treat. 2006 Sep;99(1):63-9. doi: 10.1007/s10549-006-9181-4. Epub 2006 Mar 16.
We previously found a higher incidence of circulating tumour cells (CTCs) in women with metastatic breast cancer compared to early disease. In this study, we present follow-up data to explore the prognostic significance of these findings.
CTCs were quantified by immunostaining and direct visualization after centrifugation and filtration enrichment of peripheral blood from 131 patients. Time to progression (TTP) and overall survival (OS) were defined as interval from first blood sampling to first documented disease progression, or death respectively. Lifetime data was analysed using Kaplan-Meier method, log-rank test and Cox proportional hazards model.
Follow-up data is available for 123 patients. In early disease, median CTC>or=4 best distinguished patients with shorter TTP (p=0.05, log-rank test). In univariate analysis, tumour size, grade, lymphovascular invasion (LVI) and receptor status significantly related to TTP but none of the covariates related to OS. In multivariate analysis, T stage was the only independent predictor of TTP. In metastatic disease, median CTC>or=13 optimally identified patients with shorter TTP (p=0.01). In univariate analysis, median CTC level >or=13 and prior lines of chemotherapy predicted for TTP while in multivariate analysis, median CTC level >or=13 was the only significant independent prognostic factor (p=0.02). No relationship between CTC level and OS was found in this subgroup.
Median CTC level determined in the course of treatment predicts for TTP in metastatic breast cancer. In early breast cancer, an association was found between CTC level and TTP although this did not reach statistical significance (p=0.05).
我们之前发现,与早期乳腺癌女性相比,转移性乳腺癌女性循环肿瘤细胞(CTC)的发生率更高。在本研究中,我们呈现随访数据以探讨这些发现的预后意义。
通过免疫染色以及对131例患者外周血进行离心和过滤富集后的直接可视化来定量CTC。疾病进展时间(TTP)和总生存期(OS)分别定义为从首次采血到首次记录的疾病进展或死亡的时间间隔。使用Kaplan-Meier法、对数秩检验和Cox比例风险模型分析生存期数据。
有123例患者的随访数据。在早期疾病中,中位数CTC≥4最能区分TTP较短的患者(p = 0.05,对数秩检验)。单因素分析中,肿瘤大小、分级、淋巴管浸润(LVI)和受体状态与TTP显著相关,但没有协变量与OS相关。多因素分析中,T分期是TTP的唯一独立预测因素。在转移性疾病中,中位数CTC≥13最能鉴别出TTP较短的患者(p = 0.01)。单因素分析中,中位数CTC水平≥13和既往化疗疗程可预测TTP,而多因素分析中,中位数CTC水平≥13是唯一显著的独立预后因素(p = 0.02)。在该亚组中未发现CTC水平与OS之间的关系。
治疗过程中测定的中位数CTC水平可预测转移性乳腺癌的TTP。在早期乳腺癌中,发现CTC水平与TTP之间存在关联,尽管未达到统计学显著性(p = 0.05)。