Division of Cancer, Imperial College, MRC Cyclotron Building, Imperial College Healthcare NHS Trust, Hammersmith Hospital, Du Cane Road, London W12 ONN, UK.
Br J Cancer. 2012 Jan 17;106(2):375-82. doi: 10.1038/bjc.2011.537. Epub 2011 Dec 13.
The aim of this study was to gain insight into breast cancer dormancy by examining different measures of minimal residual disease (MRD) over time in relation to known prognostic factors.
Sixty-four primary breast cancer patients on follow-up (a median of 8.3 years post surgery) who were disease free had sequential bone marrow aspirates and blood samples taken for the measurement of disseminated tumour cells (DTCs), circulating tumour cells (CTCs) by CellSearch and qPCR measurement of overlapping (96-bp and 291-bp) amplicons in circulating free DNA (cfDNA).
The presence of CTCs was correlated with the presence of DTCs measured by immunocytochemistry (P=0.01) but both were infrequently detected. Increasing cfDNA concentration correlated with ER, HER2 and triple-negative tumours and high tumour grade, and the 291-bp amplicon was inversely correlated with DTCs measured by CK19 qRT-PCR (P=0.047).
Our results show that breast cancer patients have evidence of MRD for many years after diagnosis despite there being no overt evidence of disease. The inverse relationship between bone marrow CK19 mRNA and the 291-bp amplicon in cfDNA suggests that an inverse relationship between a measure of cell viability in the bone marrow (DTCs) and cell death in the plasma occurs during the dormancy phase of breast cancer.
本研究旨在通过随时间检测不同程度的微小残留病灶 (MRD)，并与已知的预后因素相关联，深入了解乳腺癌休眠。
64 名在随访中（手术后中位数为 8.3 年）且无疾病的原发性乳腺癌患者进行了连续的骨髓抽吸和血液样本采集，用于测量播散性肿瘤细胞 (DTCs)、通过 CellSearch 检测循环肿瘤细胞 (CTCs) 以及检测循环游离 DNA (cfDNA) 中重叠 (96-bp 和 291-bp) 扩增子的 qPCR 测量。
CTCs 的存在与免疫细胞化学检测的 DTCs 存在相关 (P=0.01)，但两者均很少被检测到。cfDNA 浓度的增加与 ER、HER2 和三阴性肿瘤以及高肿瘤分级相关，而 291-bp 扩增子与 CK19 qRT-PCR 检测的 DTCs 呈负相关 (P=0.047)。
我们的结果表明，尽管没有明显的疾病证据，但乳腺癌患者在诊断后多年仍有 MRD 的证据。骨髓 CK19 mRNA 与 cfDNA 中 291-bp 扩增子之间的负相关关系表明，在乳腺癌休眠期，骨髓中细胞活力（DTCs）与血浆中细胞死亡之间存在负相关关系。
