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      Role of Circulating Tumor Cell (CTC) Monitoring in Evaluating Prognosis of Triple-Negative Breast Cancer Patients in China

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          Abstract

          Background

          Breast cancer (BC) is the most common malignant tumor in females. This study investigated the role and utility of CTC monitoring in evaluating the prognosis of triple-negative breast cancer patients.

          Material/Methods

          We enrolled 286 female triple-negative breast cancer patients who were diagnosed at and received radical resection surgery in our hospital. Peripheral venous blood samples were collected preoperatively and at 3 and 7 days postoperative, and the Cell Search system was used to detect CTC in peripheral blood. We analyzed the relationship between preoperative CTC level and clinical pathological characteristics of patients. Kaplan-Meier method was used to establish progression-free survival curves and overall survival curves, we used the log-rank test to compare the survival rate, and we explored the effects of preoperative and postoperative CTC levels on patient survival.

          Results

          Compared with preoperative levels, the average CTC content in peripheral blood of breast cancer patients was significantly increased at 3 days after surgery, and then decreased to the preoperative baseline level by 7 days after surgery. The 3-year overall survival rate and progression-free survival rate in patients with CTC >5/7.5 mL peripheral blood were significantly lower than in patients with CTC <5/7.5 mL peripheral blood detected preoperatively and at 3 and 7 days postoperatively.

          Conclusions

          Dynamic monitoring of preoperative and postoperative CTC levels can accurately predict recurrence and progression of disease, and is important in postoperative monitoring and prognosis evaluation.

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          Most cited references34

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          Triple-negative breast cancer: treatment challenges and solutions

          Triple-negative breast cancers (TNBCs) are defined by the absence of estrogen and progesterone receptors and the absence of HER2 overexpression. These cancers represent a heterogeneous breast cancer subtype with a poor prognosis. Few systemic treatment options exist besides the use of chemotherapy (CT). The heterogeneity of the disease has limited the successful development of targeted therapy in unselected patient populations. Currently, there are no approved targeted therapies for TNBC. However, intense research is ongoing to identify specific targets and develop additional and better systemic treatment options. Standard adjuvant and neoadjuvant regimens include anthracyclines, cyclophosphamide, and taxanes. Platinum-based CT has been proposed as another CT option of interest in TNBC. We review the role of this therapy in general, and particularly in patients carrying BRCA germ-line mutations. Available data concerning the role of platinum-based CT in TNBC were acquired primarily in the neoadjuvant setting. The routine use of platinum-based CT is not yet recommended by available guidelines. Many studies have reported the molecular characterization of TNBCs. Several actionable targets have been identified. Novel therapeutic strategies are currently being tested in clinical trials based on promising results observed in preclinical studies. These targets include androgen receptor, EGFR, PARP, FGFR, and the angiogenic pathway. We review the recent data on experimental drugs in this field. We also discuss the recent data concerning immunologic checkpoint inhibitors.
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            Circulating tumor cell detection predicts early metastatic relapse after neoadjuvant chemotherapy in large operable and locally advanced breast cancer in a phase II randomized trial.

            Circulating tumor cells in blood from metastatic breast cancer patients have been reported as a surrogate marker for tumor response and shorter survival. The aim of this study was to determine whether circulating tumor cells are present in the blood of patients with large operable or locally advanced breast cancer before neoadjuvant chemotherapy and after neoadjuvant chemotherapy before surgery. Blood samples of 7.5 mL were obtained on CellSave tubes from patients included in a phase II trial (REMAGUS 02). Circulating tumor cells were immunomagnetically separated and fluorescently stained by the CellSearch system. Blood from 20 metastatic breast cancer patients was used as a positive control. From October 2004 to July 2006, preneoadjuvant chemotherapy and/or postneoadjuvant chemotherapy blood samples were obtained from 118 patients. At least 1 circulating tumor cell was detected in 22 of 97 patients with preneoadjuvant chemotherapy samples (23%; 95% confidence interval, 15-31%; median, 2 cells; range, 1-17 cells). Circulating tumor cell positivity rates were 17% in 86 postneoadjuvant chemotherapy samples and 27% in all 118 patients. Persistence of circulating tumor cells at the end of neoadjuvant chemotherapy was not correlated with treatment response. After a short median follow-up of 18 months, the presence of circulating tumor cells (P=0.017), hormone receptor negativity, and large tumor size were independent prognostic factors for shorter distant metastasis-free survival. Circulating tumor cells can be detected by the CellSearch system at a low cutoff of 1 cell in 27% of patients receiving neoadjuvant chemotherapy. Circulating tumor cell detection was not correlated to the primary tumor response but is an independent prognostic factor for early relapse.
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              Single circulating tumor cell detection and overall survival in nonmetastatic breast cancer.

              Circulation of cancer cells in the blood is a mandatory step for metastasis, but circulating tumor cells (CTC) have a low metastatic efficiency in preclinical animal models. In this prospective study, we reported the clinical outcome of nonmetastatic breast cancer patients according to CTC detection. In 115 nonmetastatic patients diagnosed with large operable or locally advanced breast cancer, we prospectively detected CTC using the CellSearch system before and after neoadjuvant chemotherapy in a phase II trial (REMAGUS02). At baseline, 23% of patients were CTC positive, but only 10% had >1 CTC/7.5 ml of blood. After a median follow-up of 36 months, CTC detection before chemotherapy was an independent prognostic factor for both distant metastasis-free survival [DMFS; P = 0.01, relative risk (RR) = 5.0, 95% confidence interval (CI) 1.4-17] and overall survival (OS; P = 0.007, RR = 9, 95% CI 1.8-45). CTC detection after chemotherapy was of less significance (P = 0.07 and 0.09, respectively). Moreover, CTC detection showed interesting characteristics as an individual predictive test for metastatic relapses (sensibility 55%, specificity 81%, and global accuracy 77%). Detection of > or =1 CTC/7.5 ml before neoadjuvant chemotherapy can accurately predict OS. Our findings may change the clinical management of nonmetastatic breast cancer and indicate that the metastatic efficiency of CTC could be higher than previously reported.
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                Author and article information

                Journal
                Med Sci Monit
                Med. Sci. Monit
                Medical Science Monitor
                Medical Science Monitor : International Medical Journal of Experimental and Clinical Research
                International Scientific Literature, Inc.
                1234-1010
                1643-3750
                2017
                23 June 2017
                : 23
                : 3071-3079
                Affiliations
                Department of Breast Surgery, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, P.R. China
                Author notes
                Corresponding Author: Yanwu Zhang, e-mail: zhangyw03122@ 123456sina.com
                [A]

                Study Design

                [B]

                Data Collection

                [C]

                Statistical Analysis

                [D]

                Data Interpretation

                [E]

                Manuscript Preparation

                [F]

                Literature Search

                [G]

                Funds Collection

                Article
                902637
                10.12659/MSM.902637
                5493060
                28643770
                cee78c53-9835-4786-a0e6-b3b316ae3bce
                © Med Sci Monit, 2017

                This work is licensed under Creative Common Attribution-NonCommercial-NoDerivatives 4.0 International ( CC BY-NC-ND 4.0)

                History
                : 01 December 2016
                : 27 December 2016
                Categories
                Clinical Research

                breast,neoplastic cells, circulating,triple negative breast neoplasms

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