The Detection And Clinical Value Of Circulating Tumour Cells In Peripheral Blood In Patients With Operable Breast Cancer

Objective:To establish a multimarker comprised of cytokeratin19(CK19), human mammaglobin (hMAM) and small breast epithelial mucin (SBEM) real time quantitative RT-PCR (QPCR) platform to detect circulating tumour cells (CTC) in peripheral blood (PB) of breast cancer. To investigate the positive rate of CTC in PB in patients with operable breast cancer, the relations between the presence of CTC and the clinicopathologic characteristics of primary tumor, the impact of systemic adjuvant chemotherapy on CTC and different impact of different chemotherapy regimen.Methods:To show the baseline expression of CK19-mRNA, hMAM-mRNA, SBEM-mRNA in normal PB and to establish the cutoff threshold of positive sample, the relative gene expression (RGE) of CK19-mRNA, hMAM-mRNA, SBEM-mRNA in PB of40control subjects was detected by QPCR platform. The RGE of CK19-mRNA, hMAM-mRNA, SBEM-mRNA in PB of94patients with operable breast cancer was detected; positivity shown for the multimarker method is defined as positivity for at least one of the markers. For72patients who underwent systemic adjuvant chemotherapy, the dynamic CTC status at three different time points of chemotherapy (before chemotherapy, after three cycles of chemotherapy, after all cycles of chemotherapy) was observed. Change of CTC status was related to chemotherapy strategy.Results:For40control subjects, the mean RGE of CK19-mRNA, hMAM-mRNA, SBEM-mRNA in PB was1.16,1.88,1.26respectively; and the cutoff threshold was3.77,6.22,3.27respectively;5%(2out of40) of cases were positive. For94patients with operable breast cancer, the mean RGE of CK19-mRNA, hMAM-mRNA, SBEM-mRNAin PB was7.37,62.58,2.11respectively;49%(46out of94),34%(32out of94),13%(12out of94) of patients was positive for CK19, hMAM, SBEM respectively; the positive rate of CTC was56%(53out of94). There were no significant relations between the presence of CTC and the clinicopathologic characteristics of primary tumor (P>0.05).72patients who received systemic adjuvant chemotherapy were followed up, after3cycles of chemotherapy,47%(18out of38) patients changed into CTC negative status; after all cycles of chemotherapy, another2patients changed into CTC negative status.46%(12out of26) of patients who received FEC regimen and67%(8out of12) of patients who received T/EC regimen changed into negative CTC status.Conclusions:The multimarker real time QPCR platform has both good sensitivity and good specificity. A high positive rate of CTC was observed in patients with operable breast cancer. There was no significant relation between the presence of CTC and the clinicopathologic characteristics of primary tumor. Systemic adjuvant chemotherapy had a significant impact on CTC status in patients with operable breast cancer. There was no significant difference between different chemotherapy regimens.