Strategy and Status of Neoadjuvant Therapy for HER2-positive Breast Cancer / 肿瘤防治研究

Neoadjuvant therapy is a preoperative systemic treatment for patients with breast cancer. This therapy has greatly improved the clinical outcomes of human epidermal growth factor receptor 2 (HER2)-positive breast cancer, which is associated with poor prognosis. Currently, dual anti-HER2 antibodies, including trastuzumab and pertuzumab, combined with non-anthracycline chemotherapy is one of the standard regimens to achieve high pathologic complete response rate and satisfactory efficacy. The combination of trastuzumab with tyrosine kinase inhibitors, antibody-drug conjugate drugs, or immunotherapy combined with target therapy, under the indications of reasonable biomarkers, is effective for HER2-positive breast cancer. In this article, we briefly reviewed neoadjuvant therapy in the dual-targeting therapy era and discussed its future perspectives.

Research Progress on Immunization and Targeted Therapy for Triple-negative Breast Cancer / 肿瘤防治研究

Triple-negative breast cancer (TNBC) accounts for approximately 15%–20% of all breast cancers. Patients with TNBC have a rapidly progressive clinical course, an earlier age of onset, faster distant recurrence, and more common visceral metastases as compared with other subtypes. However, treatment of TNBC is often limited to chemotherapy and has a poor prognosis. Therefore, developing the best treatment strategy for patients is essential to reduce the burden of disease caused by TNBC. Various potential available drug targets have been discovered, as well as precision treatment and classified treatment are changing the clinical practice of TNBC, thereby indicating a new therapeutic area for TNBC in addition to traditional chemotherapy. This article reviews the systemic treatment options for TNBC in recent years, including immunotherapy and targeted therapy.

Predictive Factors and Prognostic Value of Pathologic Complete Response of Internal Mammary Lymph Nodes in Breast Cancer After Neoadjuvant Chemotherapy / 肿瘤防治研究

Objective To explore the prognostic factors of the pathological complete response of internal mammary lymph node (ipCR) after neoadjuvant chemotherapy and its effect on breast cancer prognosis. Methods We retrospectively analyzed the clinical data of 70 patients with primary breast cancer with internal mammary lymph node metastasis who received neoadjuvant chemotherapy. Patients were divided into the ipCR group and non-ipCR group based on their postoperative pathology. χ2 test, Fisher, and Logistic regression were used for univariate and multivariate analysis. Meanwhile, the Kaplan-Meier curve and Cox regression were used for prognostic analysis. Results Of 70 patients, 31 obtained ipCR (44.3%). Univariate analysis showed that the expression levels of apCR, HR, and HER2 status were related to ipCR (P < 0.05). Multivariate analysis showed that age, apCR, and HER2 status were independent predictors of ipCR (P < 0.05). The average DFS of ipCR group was better than non-ipCR group (96.0 vs. 67.1 months, P < 0.05). The risk of recurrence and metastasis was 87% lower in the ipCR group than in the non-ipCR group (HR=0.13, 95%CI: 0.04-0.44, P < 0.01). ipCR, Ki67 expression level, and breast pCR (bpCR) were independent factors affecting patients' prognosis. Conclusion There is a correlation between clinico pathological factors and ipCR after neoadjuvant chemotherapy. ipCR can be used to predict the prognosis of patients with internal mammary lymph node metastasis.

IFN-γ Inhibits Proliferation and Migration of Esophageal Squamous Cell Carcinoma by Downregulating CXCL8 Expression / 肿瘤防治研究

Objective To investigate the effect of IFN-γ on the proliferation and migration of esophageal squamous cell carcinoma cell line Eca9706 and related mechanism. Methods Cells were cultured in vitro and treated with interferon-γ. Cell morphology changes were observed under microscope, cell proliferation ability was detected by CCK-8 experiment, and cell migration ability was detected by cell scratch experiment and Transwell experiment. Real-time PCR method was used to detect the expression efficiency of chemokine CXCL8 (interleukin 8), and the ELISA experiment was used to detect the change of CXCL8 secretion. Results Compared with the blank control group, Eca9706 cells treated with different concentrations of interferon-γ did not change significantly in cell morphology. CCK8 experiment confirmed that the proliferation ability of Eca9706 cells after IFN-γ treatment was significantly reduced (P < 0.01). Cell scratch experiment found that IFN-γ significantly decreased the migration ability of Eca9706 cells (P < 0.01). Transwell experiment showed that after IFN-γ treatment, the migration ability of Eca9706 cells was significantly inhibited (P < 0.01). CXCL8 gene expression level in Eca9706 cells treated with interferon-γ was significantly down-regulated (P < 0.01), and the amount of CXCL8 secretion significantly reduced (P < 0.05). Conclusion Interferon-γ can inhibit the proliferation and migration of esophageal cancer cell line Eca9706, which may be related to its inhibition of the expression and secretion of CXCL8.

Real-world Research of Trastuzumab and Pertuzumab Combined with Chemotherapy in Neoadjuvant Treatment of HER2-positive Breast Cancer / 肿瘤防治研究

Objective To analyze the efficacy and safety of trastuzumab (H) and pertuzumab (P) combined with different chemotherapy regiments in neoadjuvant therapy for HER2-positive breast cancer. Methods We retrospectively analyzed the clinical data of the patients with HER2-positive breast cancer who received HP combined with chemotherapy as neoadjuvant therapy and completed surgery. The primary endpoint was total pathologic complete response (tpCR) (ypT0/isypN0), the secondary endpoints were breast pathologic complete response(bpCR) (ypT0/is) and axillary pathologic complete response (apCR) (ypN0), and the factors influencing pCR were analyzed. Results A total of 63 patients were included, of whom 23 were treated with TCbHP, 27 were treated with THP regimen, and 13 were treated with AC-THP. The overall tpCR rate was 65.1%, of which TCbHP was 73.9%, THP was 55.6%, and AC-THP was 69.2%. The tpCR rate of HR-negative patients was 79.2%, higher than that of HR-positive 56.4%. The overall bpCR rate was 69.8%, and apCR rate was 81.0%. Univariate analysis showed that HER2 status was a related factor affecting tpCR (P=0.023). The total effective rate by MRI was 87.3%. The level 3 and 4 toxicity of the TCbHP regimen was slightly higher than those of the THP and the AC-THP regimens. Conclusion HP combined with chemotherapy have achieved relatively high pCR. HER2 status is a related factor that affects tpCR. The adverse reactions are controllable.

Risk of Primary Lung Cancer in Breast Cancer Patients: A Systematic Review and Meta-analysis / 肿瘤防治研究

Objective To systematically evaluate the risk of primary lung cancer in breast cancer patients. Methods A computer-based search was conducted for the English literatures about the risk of primary lung cancer in breast cancer patients in Medline, Scopus and Embase databases. Two researchers independently screened the literatures, extracted the data and assessed the risk of bias. The statistical analysis was performed using the Stata 15.5 software. Results A total of 7 references were included, and the overall risk of primary lung cancer in female breast cancer patients was slightly higher than that in the general population (SIR: 1.18, 95%CI: 1.09-1.27). Subgroup analysis showed that the risk of lung cancer was significantly increased in women aged < 50 years after diagnosis of breast cancer (SIR: 1.99, 95%CI: 1.48-2.69). Conclusion Compared with the general population, the risk of primary lung cancer is increased in female breast cancer patients, especially in young women with breast cancer.

Research progress on the relationship between TET1 and tumor invasion and metastasis / 国际外科学杂志

TET1 has been discovered capable of promoting DNA demethylation by mediating 5-methylcytosine to inhibit the genesis and development of cancer.Epithelial-Mesenchymal transition is a complex cellular program in cancer progression and metastasis,whose hallmark is loss of cell polarity and cell adhesion and acquirement of migration and invasion abilities,leading tumor cells into blood vessel and lymphatic vessels to form new metastatic lesions.Epigenetics plays a vital role in epithelial-mesenchymal transition.This review focuses on the relationship of TET1,epigenetics and epithelial-mesenchymall transition,and the research progression of TET1's role in cancer invasion and metastasis.

Expression and clinical significance of KIF5A in triple negative breast cancer / 国际生物医学工程杂志

Objective To investigate the expression and clinical significance of KIF5A in triple negative breast cancer tissues.Methods The clinical and pathological data of 82 patients with triple negative breast cancer who underwent breast cancer resection were retrospectively analyzed.The expression of KIF5A in cancer tissues and corresponding adjacent tissues was detected by immunohistochemistry method,and its relationship with clinicopathological features was analyzed.Results The positive high expression rate of KIF5A in triple negative breast cancer tissues was 63.4％,but low or no expression in adjacent tissues.The abnormal expression of KIFSA was correlated with the TNM stage and Lymph node metastasis (all P＜0.05),but not associated with age,tumor grade,size and vascular tumor thrombus (all P＞0.05).Survival analysis indicated that patients with high KIF5A expression in triple negative breast cancer were significantly shorter than those with low KIF5A expression (P＜0.05).Conclusions The abnormally high expression of KIF5A in triple negative breast cancer tissues is associated with high TNM and lymph node metastasis in breast cancer,and high expression of KIF5A suggests that patients with triple negative breast cancer may have poor prognosis.

Catheter fracture of implantable central venous access port: its prevention and management / 介入放射学杂志

Objective To discuss the prevention and treatment of catheter fracture of implantable venous access port (IVAP).Methods A total of 878 adult patients,who received IVAP during the period from January 2012 to December 2012 in a single medical center,were collected.Among the 878 patients,catheter fracture occurred in 7 patients.The clinical data of the 7 patients were retrospectively analyzed.By referring to the related literature,the causes and the prevention measures for catheter fracture were discussed.Results As of November 31,2016,the catheter fracture rate of IVAP,which was implanted via internal jugular vein (IJV),was 0.8％ (7/878).The fracture occurrence time was 855-1412 days after implantation of IVAP,with a mean of 1133 days.The common fracture sites were catheter-IJV junction,catheter-IVAP base joint,and subcutaneous tunnel segment.Conclusion Catheter fracture is one of the serious complications which occur in the course of long-period use of IVAP after its implantation.Standardization of operative procedure,strengthening of the maintenance and nursing education,timely removal of IVAP,and other necessary measures can help reduce the incidence of IVAP catheter fracture and ensure the safety of patients.

Progress in the development of metabolic and breast cancer / 国际外科学杂志

With the social development,the number of obese people is increasing.Recent studies have shown that obese women to have breast cancer disease's risk is higher than normal body weight,and etabolic disorders growing threat to human health.Estrogen,aromatase have contributed to the occurrence and development of breast cancer after menopause.AMPK is a negative regulator of aromatase,it can inhibit proliferation of cancer cells by metabolic pathways.What's more metformin,resveratrol inhibited proliferation by this route has been confirmed in breast cancer cells.Here,the author do an overview of the role of obesity-related factor for postmenopausal breast tissue estrogen synthesis and metabolic abnormalities affect aromatase expression in breast.

Role of p21 and p27 in carcinogenesis and drug resistance / 国际外科学杂志

Human cancers arise from an imbalance of cell growth and cell death.Critical factors that control the balance are those regulate the cell cycle.Several molecular effectors have been identified to be able to regulate specific phases of the cell cycle,including cyclins,cyclin-dependent kinases (CDKs) and CDK inhibitors.Notably,deficiency of two G1-checkpoint CDK inhibitors-p21 (CDKN1A) and p27 (CDKN1B)-has been implicated to be correlated with initiation or progression of many human malignancies or cancer cells drug-resistance.However,contradict reports also suggested that p21 and p27 could promote tumor progression.Here,we summarized the historic and recent studies on these two CDK inhibitors,including their identification as well as their roles in carcinogenesis and drug resistance.

Rat ADSCs transfected by lentivirus vector-mediated enhanced green fluorescent protein / 中华显微外科杂志

Objective To explore the labeling method of rat adipose-derived stromal cells,and observe the stem cell characteristics and the activities of EGFP-positive adipose-derived stromal cells (EGFP-ADSCs) in vitro and in vivo.Methods ADSCs were transfected for 12 h with enhanced green fluorescent protein gene (EGFP) carried by lentivirus(Lv-EGFP) vector at different value of MOI (0,5,10,25,50,100,respectively).The rate of EGFP expression and fluorescence intensity were evaluated by flow cytometric analysis and fluorescence microscopy,and cell viability was detected by MTT-test after transfection.Secondly,cells were exposed either to adipogenic medium or osteogenic medium,then stained with Oil Red O and Alizarin Red S.Cell growth was investigated on frozen longitudinal sections when EGFP-ADSCs were injected into acellular nerves to build tissue-engineered peripheral nerves repairing sciatic nerve defects in rats for 1 week in vivo.Results EGFP-positive rate and fluorescence intensity peak at 4 days after transfection.The rate of EGFP expression was 0.13％,31.09％,75.33％,92.66％,96.70％,98.38％ for MOI =0,1,5,25,50,100,respectively.The positive rate between the experimental group and control (MOI =0) existed significantly difference (P ＜ 0.05) ; the difference between MOI =1,5 groups and MOI =25,50,100 groups were also observed (P ＜ 0.05).There was no statistical difference in EGFP-positive rate and cell proliferation activity among MOI =25,50,100 groups (P ＞ 0.05).MOI =25 was chosen as best scheme to transfect ADSCs for subsequent experiments.Osteogenic and adipogenic differentiation for 20 days,orange calcium deposits,orange-red lipid droplets were seen in EGFP-ADSCs after Alizarin red and oil red O staining.At 1 week in vivo,EGFP-ADSCs evenly distributed and became fusiform on frozen longitudinal sections.Conclusion Lv-EGFP transfection does not affect the ADSCs activity and their osteogenic and adipogenic differentiation,so could be as a tracing method for ADSCs-tissue-engineered peripheral nerves repairing nerve defects.

Research on epidermal growth factor receptor in breast cancer / 国际外科学杂志

Decades researches of molecular oncology have found some moleculars which can promote tumor growth and help cancer surrive.This brings new hope for the treatment of tumors.Epidermal growth factor receptor (EGFR) is the first important molecular to inhibit tumor growth.Fifty percent triple negative breast cancer (TNBC) and inflammatory breast cancer (IBC) overexpress EGFR.EGFR and its downstream pathway can regulate epithelial-mesenchymal transition,promote tumor cell migration.EGFR therapy can improve the chemosensitivity of TNBC cells,apoptotic signal transduction occur.These studies suggest that the EGFR targeted therapy may have an important role in the treatment of TNBC and IBC.

Expressions of steroid sulfatase in breast cancer tissues and normal breast tissues and its significance / 肿瘤

Objective:To investigate the mRNA and protein expressions of steroid sulfatase (STS) in breast cancer tissues and normal breast tissues, and analyze its relationship with clinicopathologic characteristics. Methods:The mRNA and protein expressions of STS, in 40 cases of breast cancer tissues and corresponding paracancerous normal breast tissues, were examined by reverse transcription-polymerase chain reaction(RT-PCR)and immunohistochemistry. The correlation of STS expression level with clinicopathologic characteristics was analyzed. Results:STS protein was mainly expressed in the cytoplasm of breast carcinoma cells and epithelial cells in normal breast glands, but not in the stroma. It could be detected in the nucleus of carcinoma cells in 3 cases of breast cancer tissues, which was pathologically classified as invasive ductal carcinoma, invasive lobular carcinoma, and invasive micropapillary carcinoma. STS was not observed in interstitial tissues of breast glands. STS protein expression had positive correlation with its mRNA expressing level. The positivity of STS was 70.0% in breast cancer tissues, significantly higher than that of normal breast tissues (42.5%). The difference was significant (P =0.013). Stratified analysis showed that the positive rates of STS protein were significantly higher in premenopausal patients, the patients with lymph node metastasis, and those with advanced breast carcinoma than those in the matched normal breast tissues (P<0.05). Conclusion:Breast cancer tissues highly expressed STS protein to stimulate local estrogen production, thereby enhancing the progression and migration of breast cancer cells. In addition, as the tumor growth, locally biosynthesized estrogens may play more and more important roles.

The role of bone marrow micrometastasis in breast cancer in judging prognosis / 肿瘤研究与临床

Objective To investigate the relationship between bone marrow micrometastasis of patients with breast cancer and clinical pathological parameters, some molecular markers as well as prognosis.Methods The expression of hMAM mRNA in BM of patients with breast cancer was detected by RT-PCR.The expressions of ER, PR in cancer tissues were detected by immunohistochemical SP method. Results About 38.2 % positive expression rate of hMAM mRNA in 102 patients with stage Ⅰ -Ⅳ breast cancer was found.The expression of hMAM increased more in patients with T2-3 (＞2 cm) tumors than T1 (≤2 cm) (P =0.001)and with stage Ⅱ ,Ⅲ than stage Ⅰ (P =0.001). The expression of hMAM in the BM of breast cancer with grade I was lower than that of grade Ⅱ or Ⅲ (P =0.014). The expression of hMAM in the BM was related to the pathological type (P =0.032) and the axillary lymph node metastasis (P =0.001). The expressions of hMAM in BM were much higher with ER negative in breast cancer tissues (P ＜0.05). There was a correlation between patients with positive expression of hMAM in BM and distant metastasis (P =0.009). Conclusion The micrometastasis in BM is correlated with some clinical pathological parameters and some tumor markers. The patients with positive expression of hMAM in BM have more chances with distant metastasis and poor prognosis. The detection of micrometastasis may be as one of targets to predict the prognosis of breast cancer.

Preparation of tumor-specific CTLs and their therapeutic effects on bone marrow micrometastasis of breast cancer / 中国肿瘤生物治疗杂志

Objective: To prepare auto-tumor-specific cytotoxicity T lymphocytes (CTLs) of breast cancer patients and to observe their therapeutic effects on bone marrow micrometastasis (BMM) of breast cancer. Methods: BMM in 82 patients with primary breast cancer (stage Ⅰ to Ⅲ) , who were treated in the Fourth Affiliated Hospital of Hebei Medical University from March to December in 2007 (all the patients signed paper of informed consent), was exmined by flow cytometryusing CK18 and CK19 as marker. Twenty-three patients with BMM were randomly divided into two groups: 17 patients were treated with tumor-specific CTLs (therapy group), and 6 patients were treated with IL-2 (control group). Tumor-specific CTLs were induced in vitro from axillary lymph nodes and peripheral blood of breast cancer patients in ther-apy group, and were reinfused into the same patient 10-14 days after operation. The therapeutic effects of tumor-specific CTLs on BMM of breast cancer patients were observed. Results: Twenty-three cases (28.05%) in 82 breast cancer patients were BMM positive as detected by FCM. BMM positive rates increased with the increase of clinical TNM stages and histological grades of breast cancer, and decreased with the increase of ER and PR protein expression in cancer tis-sues. Dendritic cells (DCs) were successfully isolated and induced from the peripheral blood of breast cancer patients. Tumor-specific CTLs were induced by co-culturing lymphocytes from axillarey lymph nodes with auto-tumor antigen-im-pulsed DCs. Fourteen cases in the therapy group became negative of BMM after treatment with tumor-specific CTLs (14/ 19, 82.35%). Only one case in the control group became negative of BMM after treatment with IL-2 (1/6, 16.67%, P=0.00028). Conclusion: Tumor-specific CTLs have been successfully prepared and they show a satisfactory therapeu-tic effect on bone marrow micrometastasis of breast cancer.

Expression of Skp2 and P21 in the Process of Breast Hyperplasia Cancerating and its Significance / 医学研究杂志

Objective To investigate the expression and role of Skp2 and P21 in the process of breast hyperplasia cancerizing.Methods The expression of Skp2 and P21 protein in normal breast tissue,adenosis of breast,breast atypical hyperplasia,breast hyperplasia cancerization,and breast cancer were detected by immunohistochemical staining SP method.Results(1) The expression of Skp2 and P21 in normal breast tissue and adenosis of breast was negative,the positive staining rate of Skp2 and P21 in breast atypical hyperplasia was 25.71% and 37.14%,in breast hyperplasia cancerization 63.16% and 73.68%,breast cancer,75% and 100% respectively.The contradistinction between breast atypical hyperplasia and breast hyperplasia cancerization was of significant statistically.But there was no statistical significance between breast hyperplasia cancerization and breast cancer.(2) The expression of P21 could lead to accelerated expression of Skp2.(?2= 10.024,P=0.002).There was a significant positive correlation between Skp2 and P21(r=0.563,P=0.000).Conclusion Skp2 and P21 are involed in the early stage of breast cancer and contribute to the maligant phenotype without affecting infiltration.Both of them are danger factors for breast hyperplasia cancerizing and contribute to malignant process from normal breast tissue and atypical hyperplasia to breast cancer.They are effective indicators for prognosis of breast hyperplasia.

Study on DC loaded with freeze-thrawing antigen from breast cancer cells to the specific cytotoxicity of CTL in vitro / 中国免疫学杂志

Objective:To study the influence of the DCs from mononuclear cells in axillary draining lymph nodes of patients with breast cancer to the cytotoxicity of the antigenic specific CTLs stimulated by freeze-thrawing antigen from breast cancer cells in vitro.Methods:The mononuclear cells were isolated from axillary draining lymph nodes,and were cultured with cytokines to induce DCs and tumor draining lymph node cells(TDLNCs) respectively.DCs stimulated by the auto-breast cancer freeze-thrawing antigen(DCs-Ag).TDLNCs were co-cultured with DCs-Ag to derive tumor antigenic specific CTLs(DC-Ag-TDLNC).Then the cytotoxicty of specific CTLs to auto-breast cancer cells and MCF-7 cells was detected.Results:The cytotoxicity of DC-Ag-TDLNC,DC-TDLNC and TDLNC to the auto-breast cancer cells was 67.64%、31.25% and 26.36% respectively,P0.05.Conclusion:Typical DCs can be induced from the mononuclear cells from axillary draining lymph nodes after stimulated with cytokines(rhGM-CSF,rhIL-4 and TNF-?).The DCs possess stronger antigen presentation and can obviously increase the killing activity of tumor antigen specific CTLs to auto-breast cancer cells.