To explore the change of circulating tumor cells (CTCs) in peripheral blood after neoadjuvant chemotherapy (NAC) and its relationship with the efficacy of NAC.

According to the inclusion and exclusion criteria, this study retrospectively included 86 breast cancer patients who underwent NAC in the Department of Breast Surgery, the Fifth Affiliated Hospital of Zhengzhou University from July 2018 to July 2019. Their peripheral venous blood (7.5 ml) was collected before and after NAC. The number of CTCs was measured using CanPatrol?CTC technique. According to the expression of related markers of epithelial-mesenchymal transition (EMT), CTCs were divided into three subtypes: epithelial CTCs, mesenchymal CTCs and biphenotypic (epithelial/mesenchymal) CTCs. The number of CTCs was expressed as M(P₂₅, P₇₅) because of skewed distribution. χ² test was used to analyze the relationship between CTCs before NAC and clinicopathologic characteristics of patients, and Wilcoxon signed rank sum test was used to compare the number of CTCs in different subtypes before and after chemotherapy. The Miller-Payne pathological grading system was used as the gold standard to evaluate the efficacy. The Kappa test was used to evaluate the consistency between the test results of CTCs in different subtypes and the gold standard in efficacy evaluation.

(1)The mesenchymal CTCs were closely related to the expression of HER-2 and proliferative nuclear antigen Ki-67. The patients with HER-2 positive had a significantly higher positive rate of mesenchymal CTCs compared with patients with HER-2 negative[42.1%(16/38)vs 12.5%(6/48), χ²=9.765, P=0.002]; the patients with Ki-67 ≥15% had a significantly higher positive rate of mesenchymal CTCs compared with patients with Ki-67<15%[39.6%(19/48)vs 7.9%(3/38), χ²=11.187, P=0.001]. (2)The total number of CTCs showed no significant difference before and after NAC[8.0 (6.0, 12.0) cells/7.5 ml vs 9.0 (6.0, 13.0) cells/7.5 ml, Z=-1.214, P=0.225]. According to the results of postoperative pathological examination, the patients were divided into the NAC-effective group (61 cases) and the NAC-ineffective group (25 cases). The number of mesenchymal CTCs and biphenotypic CTCs in the NAC-effective group after NAC was significantly lower than that before NAC[2.0(1.0, 3.0) cells/7.5 ml vs 3.0(2.0, 5.0) cells/7.5 ml, Z=-4.914, P<0.001; 2.0(1.0, 4.5) cells/7.5 ml vs 3.0(2.0, 5.0) cells/7.5 ml, Z=-3.197, P=0.001], while the number of epithelial CTCs showed no significant difference [3.0(1.0, 5.0) cells/7.5 ml vs 2.0(1.0, 4.0) cells/7.5 ml, Z=-0.728, P=0.467]; In the NAC-ineffective group, the number of mesenchymal CTCs after NAC was significantly higher than that before NAC[3.0(2.0, 6.0) cells/7.5 ml vs 2.0(1.0, 4.0) cells/7.5 ml, Z=-2.351, P=0.019], and the number of epithelial and biphenotypic CTCs showed no significant difference [2.0(2.0, 4.0) cells/7.5 ml vs 2.0(0.0, 4.0) cells/7.5 ml, Z=-0.701, P=0.438; 3.0(1.5, 5.0) cells/7.5 ml vs 2.0(1.0, 4.0) cells/7.5 ml, Z=-1.535, P=0.125]. (3)The Kappa test was used to analyze the consistency between the test results of epithelial, mesenchymal and biphenotypic CTCs and the results of pathological evaluation (Kappa=0.194, 0.749, 0.376; all P<0.050), indicating a high consistency between test result of mesenchymal CTCs and pathological result.

In breast cancer patients, the change in total number of CTCs can not accurately evaluate the efficacy of NAC. Based on the number and subtype of CTCs, clinicians can make a better judgment on the efficacy of NAC and adjust the treatment plan accordingly.