Influence of Neoadjuvant CAF Chemotherapy on Serum TSGF, CA15-3 and CA125 in Patients with Breast Cancer
ZHAO Chang-xiao, DONG Li, ZHANG Jiang, Ren Yi*
Department of Breast Surgery, Xuzhou Cancer Hospital, Xuzhou, Jiangsu, 221005, China
*Corresponding Author: REN Yi, E-mail: rxk666@163.com
Abstract

Objective: To investigate the influence of neoadjuvant CAF chemotherapy on serum tumor specific growth factor (TSGF), carbohydrate antigen15-3 (CA15-3), and CA125 in patients with breast cancer.Methods: A total of 70 patients with breast cancer were selected and randomly divided into observation group and control group. Control group was conducted with conventional radical mastectomy but didn’t receive the chemotherapy intervention, while observation group was first given neoadjuvant chemotherapy (CAF regimen): intravenous injection of 500 mg/m2 cyclophosphamide and 500 mg/m2 5-fluorouracil on the d1 and d8, intravenous injection of 30 mg/m2 adriamycin on the d1 day, 21 d as one cycle, 2 cycles in total. The efficacy of two groups was evaluated after treatment. The levels of TSGF, CA15-3, and CA125 of two groups before, 4 weeks and 12 weeks after treatment were compared. And the correlation between TSGF and CA125, TSGF and CA15-3, CA125 and CA15-3 was analyzed.Results: The overall response rate (ORR) and disease control rate (DCR) were higher in observation group (68.6% and 88.6%) than control group (42.6% and 72.3%), but only with the statistical difference in ORR between two groups (P<0.05). The levels of TSGF, CA15-3 and CA125 all decreased significantly in both groups after treatment compared with pretreatment, and observation group receiving neoadjuvant chemotherapy before surgery decreased more significantly than control group after treatment (P<0.01). There was positive correlation between TSGF and CA125 (r=0.493, P=0.003), between TSGF and CA15-3 (r=0.625, P=0.000), between CA125 and CA15-3 (r=0.741, P=0.000).Conclusion: Neoadjuvant CAF chemotherapy has good effects on the treatment of patients with breast cancer, which may be related to the influence of neoadjuvant CAF chemotherapy on the levels of TSGF, CA15-3 and CA of patients.

Key words: Breast cancer; Neoadjuvant chemotherapy CAF regimen; TSGF; CA15-3; CA125
Introduction

Breast cancer is one of the major malignant tumors influencing women’ s life and health worldwide, and the second leading cause of cancer death in women [1, 2]. In the 1960’ s, Fisher et al. [3] proposed that breast cancer was a kind of systemic disease, for which the treatments included systemic therapy and local therapy. In 1982, Frei [4] put forward the concept of neoadjuvant chemotherapy, referring to systemic cytoxic drug therapy before operative treatment or radiotherapy. At present, neoadjuvant chemotherapy has become a popular comprehensive approach for women with breast cancer, and been widely used in clinical practice, especially achieving good effects in early-stage or locally advanced breast cancer when compared with similar treatment after operation [5, 6, 7]. Neoadjuvant chemotherapy can degrade and downstage the tumor before surgery, thus increasing the opportunity of successful surgery. However, it is still controversial to rationally formulate chemotherapy regimens [8]. Theoretically, the effective combined chemotherapy is used prior to surgery or radiotherapy that kills a large quantity of tumor cells, and then eliminates the residual tumor cells through exairesis or radiotherapy. It is also feasible for cancer cells insensitive to chemotherapy. Therefore, this study was to employ neoadjuvant CAF chemotherapy to treat patients with advanced breast cancer, so as to explore the efficacy of neoadjuvant CAF chemotherapy, its influence on the levels of serum TSGF, CA15-3 and CA125 of patients as well as the correlation between TSGF, CA125 and CA15-3.

Materials and Methods
General data

A total of 70 patients in Xuzhou Cancer Hospital from Jan., 2013 to Jan., 2015 were selected and all patients were diagnosed as advanced breast cancer by clinical examinations and randomly divided into observation group (n=35) and control group (n=35). Patients in observation group aged 32-63, with the median age of 45. There were 16 cases stage IIIa and 19 in stage IIIb. Breast cancer of all patients was mainly distributed in the unilateral breast, 18 in the right breast and 17 in the left breast. Patients in control group aged 31-65, with the median age of 47. There were 15 cases in stage IIIa and 20 in stage IIIb; 18 in the right breast and 17 in the left breast. All patients in two groups were female. Two groups with no difference in age, staging, pathological patterns (P> 0.05), were comparative. This study was approved by Ethics Committee of Xuzhou Cancer Hospital. All patients agreed to participate in this study, and signed the informed consent.

Methods

Treatment: All patients could receive surgery. Control group was conducted with conventional radical mastectomy but didn’ t receive the chemotherapy intervention. Observation group was first given neoadjuvant chemotherapy (CAF regimen): intravenous injection of cyclophosphamide 500 mg/m2 and 5-fluorouracil 500 mg/m2 on d1 and d8, intravenous injection of adriamycin 30 mg/m2 on d1, 21 d as one cycle, 2 cycles in total. After surgery, both groups were conducted with 2 cycles of the above chemotherapy intervention.

Detection of serum TSGF, CA15-3 and CA125: Venous blood was collected before and after chemotherapy and centrifuged. Radioimmunoassay was used for detecting the level of serum tumor specific growth factor (TSGF), carbohydrate antigen15-3 (CA15-3), and CA125 before, 4 weeks and 12 weeks after treatment. Ria kit was provided by Newland Biotech. The operation was conducted strictly according to kit instructions.

Observational indexes and evaluation criteria

The efficacy of two groups was observed. The levels of TSGF, CA15-3, and CA125 before, 4 weeks and 12 weeks after treatment were compared.

The efficacy was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST), including complete remission (CR), partial remission (PR), stable disease (SD) and progressive disease (PD). The objective response rate (ORR) = (CR+PR) cases/total cases× 100%. The disease control rate = (CR+PR+SD) cases/total cases× 100%.

statistical analysis

All data were processed by SPSS15.0 software package. The measurement data were presented as (ヌ± S) and analyzed using t test. The enumeration data were analyzed using χ 2 test. The levels of TSGF, CA15-3 and CA125 of patients in two groups before and after treatment were presented in a histogram. P< 0.05 was considered statistically significant.

Results
The short-term efficacy of two groups

In observation group, there were 10 CR, 14 PR, 7 SD, and 4 PD, the ORR was 68.6% (24/35), and DCR was 88.6% (31/35). In control group, there were 7 CR, 8 PR, 11 SD, and 9 PD, the ORR was 42.6% (15/35), and DCR was 74.3% (26/35). The ORR and DCR were higher in observation group than control group, but only with the statistical difference in ORR between two groups (P< 0.05).

Comparison of TSGF, CA15-3 and CA125 of patients between two groups before and after treatment

The levels of TSGF, CA15-3, and CA125 in two groups before and after treatment were shown in Figure 1.

Figure 1 The Levels of TSGF, CA15-3 and CA125 of Patients in two Groups Before and After Treatment.
(1) P> 0.05 vs. control groups treatment before, (2) * * P< 0.01 vs. treatment before, (2) P< 0.01 vs control group at different time point after treatment. As was seen in Figure 1, the levels of TSGF, CA15-3 and CA125 all decreased significantly in both groups after treatment, but observation group receiving neoadjuvant chemotherapy before surgery decreased more significantly than control groups.

Correlations between TSGF and CA125, TSGF and CA15-3, CA125 and CA15-3

There was positive correlation between TSGF and CA125 (r=0.493, P=0.003), between TSGF and CA15-3 (r=0.625, P=0.000), between CA125 and CA15-3 (r=0.741, P=0.000) (Figures 1-3).

Figure 2 Correlation Between the Levels of TSGF and CA125.

The Spearman linear analysis showed a positive correlation between them (r=0.493, P=0.003).

Figure 3 Correlation Between the Levels of TSGF and CA15-3.

The Spearman linear analysis showed a positive correlation between them (r=0.625, P=0.000).

Figure 4 Correlation Between the Levels of CA125 and CA15-3.

The Spearman linear analysis showed a positive correlation between them (r=0.741, P=0.000).

Discussion

Neoadjuvant chemotherapy is one of the important systemic treatment approaches for breast cancer. Clinically, it is mainly used for patients with early and middle-stage operable breast cancer or locally advanced breast cancer (IIb-IIIb) [9]. For the former, it mainly increases the chance of breast-conserving surgery, and for the latter it mainly degrades the staging of the advanced tumor, thus improving the resectable rate and breast-conserving surgery for women who would otherwise need a masdtectomy [10]. Kim et al. [11] reported in their study that neoadjuvant chemotherapy had obvious advantages in the treatment of breast cancer in that it could kill the subclinical metastatic lesion as early as possible, degrade primary lesions and regional lymph nodes, and help improve the successful rate of operation. The CR and survival rate of patients are improved after receiving neoadjuvant chemotherapy [12]. CAF regimen is a typical chemotherapy plan for breast cancer [13]. In this study, we used CAF regimen to treat patients in observation group, and found the tumor reduced to different extent, which narrowed the scope of operation, and the ORR was higher in observation group (68.6%) than control group (42.6%), proving the CAF chemotherapy gained better effects.

Tumor markers refer to large molecular weight proteins like tumor-associated antigens, enzymes and ectopic hormones closely associated with the occurrence and development of tumors. They can be detected in blood and other body fluid [14]. At present, tumor markers play an important role in the diagnosis of malignant tumors, and their detection is also an important means to assist clinicians to diagnose breast cancer at an early stage, effectively assess the efficacy, and predict the prognosis of patients [15, 16, 17]. TSGF is a kind of carbohydrate and metabolic substance associating with tumor growth, which plays an assistant role in the growth and metastasis of tumors. It is also an important fundamental substance of angiogenesis in tumors [18]. CA15-3 is a vital important specific marker for breast cancer, located on the surface of tumor cells [19]. The positive rate of CA15-3 could be up to 30%-50%. The more and larger metastatic lesions of breast cancer cells are, the higher the level of CA15-3 is, so it can be regarded as the specific tumor marker for monitoring recurrence of breast cancer after treatment [20, 21]. CA125 is a specific tumor marker for detecting endometrial cancer and ovarian cancer, with the in-depth study of it, CA125 is found to be expressed in breast cancer and other non-gynecologic cancer, so it has a certain referable value in the diagnosis and treatment of breast cancer [22].

Therefore, we detected the levels of TSGF, CA125 and CA15-3 before and 4 weeks and 12 weeks after treatment to evaluate the efficacy of neoadjuvant therapy in patients with advanced breast cancer. The results in our study showed that the levels of TSGF, CA15-3 and CA125 all decreased significantly in both groups after treatment, but observation group receiving neoadjuvant chemotherapy before surgery decreased more significantly than control groups, indicating that the levels of three tumor markers were significantly improved after receiving neoadjuvant chemotherapy prior to surgery. Additionally, the other results of this study showed that there was positive correlation between TSGF and CA125 (r=0.493, P=0.003), between TSGF and CA15-3 (r=0.625, P=0.000), between CA125 and CA15-3 (r=0.741, P=0.000).

In conclusion, neoadjuvant CAF chemotherapy has good effects on the treatment of patients with breast cancer, which may be related to the influence of neoadjuvant CAF chemotherapy on the levels of TSGF, CA15-3 and CA of patients.

Declaration

All authors of this article declare that they have no conflict of interest.

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