The study involved 121 patients aged 21 to 80 years who underwent comprehensive treatment in ZOKOD (Zaporozhye Regional Clinical Oncology Dispensary) in 2011-2013. (82 patients) and in 4GB of the Dnieper in 2014-2016. (39 patients) in a hospital or in an outpatient chemotherapy room. In all patients, I-IV breast cancer was diagnosed, which was verified morphologically.
It was found that during the tumor progression in patients with breast cancer the phenotypic status of the receptors of malignant cells changed. Tumor cells lost receptors to estrogens and progesterone (the level of median expression of the ER decreased from 90 (0-100) in the primary tumor to 40 (0-90) in the sites of metachronous metastases (P = 0.039), the expression of the RP decreased from 50 (0-100) in the primary tumor to 0 (0-80) in metachronous metastases (P = 0.035), while the expression levels of Her2 and Ki-67 increased in stages of the tumor disease (the level of median Her2 expression rises from 0 (0-2) in the primary tumor to 1 (0-3) in the foci of metachronous metastases, (P = 0.039), the level of median Ki-67 expression rises from 10.5 (8.0-23.0) in the primary tumors to 35.0 (9.5-62.5) in the foci of metachronous metastases), which leads to a more aggressive course of the tumor disease.
CТC in the blood was found in 83 (68.6%) patients, of which 7 (41%) had stage 1 disease, 52 (71%) had stage 2, 13 (72% ), at the 4th stage in 12 (94%) patients. Phenotypically, in the detected CТC compared with the primary focus, the expression of ER and RP is significantly reduced (the level of median expression of the ER decreases from 3 (0-3) in the primary tumor to 1 (0-2) in the sites of metachronous metastases (P <0.001), the expression of the RP decreases from 1 (0-3) in the primary tumor to 0 (0-1) in metachronous metastases (P <0.001). The expression level of Her2 in the CТC compared with the primary fallout remained unchanged.
As a predictor of the appearance of CTC in the blood, the presence of synchronous metastases was determined (from the multiplication to each stage of N (from 0 to 3), the occurrence of CTC increases by 5.3 times, P = 0.001), the presence of metachronous metastases (the chance of appearance in the blood of CSCs increases by 3.24 times (odds ratio - 3.24, P = 0.017) and Her2 expression by tumor cells (odds ratio - 1.70, P = 0.017), which indicates that with the multiplying of Her2 expression level (from 0 up to 3+) the chance of a CSC occurrence increases by 1.7 times.
The three-year recurrence-free survival was studied in three groups of patients: "No CТC" (number of CТC 0 - +), "with CТC" (number of CTC ++ - ++++), "All patients". The three-year recurrence-free survival of patients with metastatic breast cancer with the presence of CTC is 18.4%, without CТC - 36.6% (p <0.001), the difference between "No CТC" and "All patients" was statistically unreliable.
In in 6 (42,8%) patients out of 14 with metastatic breast cancer in CTC, expression of Ki-67 was detected. In 2 (33.3%) of these patients, the expression in CTC, of the expression of chemoresistant markers (P-Glycoprotein MRP, BCRP)
