Abstract:

Objective

To explore the relationship between circulating tumor cell (CTC) in peripheral blood of breast cancer patients and the curative effect of neoadjuvant chemotherapy for breast cancer.

Methods

Totally 94 breast cancer patients in Department of Breast and Thyroid Surgery, Research Institute of Surgery, Daping Hospital, Third Military Medical University, from December 2014 to June 2016 were enrolled for a prospective study according to the inclusion and exclusion criteria. Venous blood samples of 5 ml was collected from upper limb in healthy side of patients before and after neoadjuvant chemotherapy (NAC), and isolation by size of epithelial tumor cells (ISET) was adopted in detecting circulating tumor cells in peripheral blood. Conventional imaging examination was given before the first chemotherapy and after 2-4 cycles of NAC to evaluate the curative effect of NAC according to Response Evaluation Criteria in Solid Tumors(RECIST guideline version). If the chemotherapy was ineffective, the patients shifted to surgical treatment, otherwise,the patients completed 6 cycles of NAC and then underwent surgical treatment. According to pathological evaluation standard of Miller-Payne as a gold standard for curative effect evaluation, CTC reduction was defined as effective and CTC invariant or increase was defined as ineffective by the changes of CTC number after NAC.χ² test was used to analyze the association between the presence of CTC and clinicopathological characteristics of breast cancer patients. McNemar test was used to compare the positive rate of CTC before and after NAC.The number of CTC before and after treatment were expressed as M(P₂₅ -P₇₅) because of its skewed distribution, and compared using Wilcoxon signed-rank test. Kappa test and McNemar test were used to evaluate the consistency between CTC detection and pathological gold standard. The sensitivity and specificity were calcuted to evaluate the CTC detection.

Results

The detection rate of CTC in peripheral blood before NAC was 62.8% (59/94). The detection rate of CTC in HER-2 positive patients was significantly higher than that in HER-2 negative patients [80.0%(36/45) vs 46.9%(23/49),χ²=10.971,P＜0.001]. The detection rate of CTC in patients with high Ki67 expression was significantly higher than that in patients with low Ki67 expression [77.4%(41/53) vs 44.0%(18/41), χ²=10.971, P＜0.001]. The detection rate of CTC and the number of detected CTC after NAC were significantly lower than those before NAC [23.4%(22/94) vs 62.8%(59/94), χ² =35.100,P＜0.001; 0(0-0)vs 3(0-6), Z=-6.120,P＜0.001]. The sensitivity of CTC detection in NAC efficacy evaluation was 76.5%(39/51) and the specificity was 69.8%(30/34), and the consistency with the gold standard was described as moderate (Kappa=0.463, P＜0.001).

Conclusions

The alteration of CTC after NAC is related to the curative effect of NAC. CTC detection has the potential to become a new way to assess the efficacy of NAC.

Key words: Breast neoplasms, Chemotherapy,adjuvant, Neoplastic cells,circulating