Circulating Tumor Cell:an Evolving Role Played In The Tumor Response To Neoadjuvant Chemotherapy

Objective:The aim of this study was to evaluate the circulating tumor (CTC) levels at the time of primary diagnosis during the neoadjuvant chemotherapy (NCT) in the peripheral blood of breast cancer patients and to correlate circulating tumor cell detection with tumor response to adjuvant chemotherapy.Thereby, confirming the assumption that monitoring the changes in CTC during first cycles of therapy can help to predict the adequate response to treatment may provide us clinical evidence toward individualized treatment.Methods:Included in the study were56patients who were diagnosed by pathology using disposable biopsy needle between June2011and July2012with primary invasive breast cancer stages Ⅱ～Ⅲ. These patients received at least2cycles of TEC-based neoadjuvant chemotherapy (docetaxel, epirubicin, and cyclophosphamide). We evaluated response of neoadjuvant chemotherapy according to RECIST (response evaluation criteria in solid tumors). And we detected circulating tumor cells (CTCs) with the expression of CK19mRMA and SBEM mRNA in peripheral blood of patients with breast cancer using quantitative reverse transcriptase PCR (qRT-PCR). To investigate the relationship between circulating tumor cell and the response to neoadjuvant chemotherapy and the clinicopathological characteristics, SPSS17.0software was used for statistical analysis.Results:1. Among56patients,23(41.1%) was detected CK19mRNA positive and25/56(44.6%) was detected SBEM positive before neoadjuvant theropy.Compared with the contol group, the detection of CK19mRNA and SBEM mRNA in breast cancer patients has higher sensitivity (P<0.05);2. The detection rate of CTC reached to64.3%after combining the two maker genes, which is much higher than detected by a single maker gene(P=0.014; P=0.037);3. There was correlating CK19and SBEM expression with clinical stage and axillary lymph node status (P=0.001; P=0.001),but there was no significant difference in age, tumor location, tumor size,and the expressions of estrogen receptor(ER), progesterone receptor(PR),HER-2and Ki-67(P>0.05);4. After adjuvant chemotherapy,both the CK19and SBEM poitive cases has reduced.Meanwhile we found that the expression levels of the two genes has reduced significantly (P=0.001; P=0.000);5. The total clinical response rate was62.5%(35/56),among which the positive-positive and negative-positive groups reached higher clinical reponse rate compared with positive-positive and negative-positive groups (P=0.004;P=0.002);6. The patients who achieved clinical reponse had more significant reduction of CK19and SBEM expression levels than those had no response to treatment(P=0.007; P=0.005).This was either significant in positive-positive group during NCT.Conclusions:1. Disseminated breast tumour cells which were detected by CK19and SBEM were evaluated by quantitative real-time PCR and the maker genes were both proved to be specific;2. CTC tends to be detected more likely in patients with node-positive and later clinical stage. And there was no correction between CTC and biological prognostic factors,such as ER、PR、HER-2and Ki-67;3. The expression rate of CTC decreases significantly after neoadjuvant chemotherapy was preformed, and the changes of CTC status during NCT has correlatd with the efficiency of NCT which indicates that CTC can be used to evaluate the the adequate response to NCT.