Radiotherapy refusal in breast cancer with breast-conserving surgery.

BACKGROUND: Although radiotherapy after breast-conserving surgery has been the standard treatment for breast cancer, some people still refuse to undergo radiotherapy. The aim of this study is to identify risk factors for refusal of radiotherapy after breast-conserving surgery. METHODS: To investigate the trend of refusing radiotherapy after breast-conserving surgery in patients with breast cancer using the Surveillance, Epidemiology, and End Results database. The patients were divided into radiotherapy group and radiotherapy refusal group. Survival results were compared using a multivariate Cox risk model adjusted for clinicopathological variables. Multivariate logistic regression was used to analyze the influencing factors of patients refusing radiotherapy after breast-conserving surgery and a nomogram model was established. RESULTS: The study included 87,100 women who underwent breast-conserving surgery for breast cancer between 2010 and 2015. There were 84,948 patients (97.5%) in the radiotherapy group and 2152 patients (2.5%) in the radiotherapy refusal group. The proportion of patients who refused radiotherapy after breast-conserving surgery increased from 2.1% in 2010 to 3.1% in 2015. The Kaplan-Meier survival curve showed that radiotherapy can improve overall survival (p < 0.001) and breast cancer specific survival (p < 0.001) in the patients with breast-conserving surgery. The results of multivariate logistic regression showed that age, income, marital status, race, grade, stage, subtype and chemotherapy were independent factors associated with the refusal of radiotherapy. CONCLUSIONS: Postoperative radiotherapy can improve the benefits of breast-conserving surgery. Patients with old age, low income, divorce, white race, advanced stage, and no chemotherapy were more likely to refuse radiotherapy.

Human epidermal growth factor receptor 2 inhibits activating transcription factor 7 to promote breast cancer cell migration by activating histone lysine demethylase 1.

BACKGROUND: Receptor tyrosine-protein kinase erbB-2 (human epidermal growth factor receptor 2 [HER2])-based therapies can improve the prognosis of HER2-positive breast cancer (BRCA) patients; however, HER2-positive patients with distal metastasis do not gain significant clinical benefit from molecular targeted therapy. MATERIALS AND METHODS: A database analysis, immunohistochemistry, and quantitative real-time polymerase chain reaction were used to evaluate the expression of activating transcription factor 7 (ATF7) and its clinical value. A transwell chamber assay was used to assess migration and cell signaling was assessed by immunoblotting. RESULTS: ATF7 was expressed at a low level in HER2-enriched BRCA specimens compared with normal or HER2-negative specimens, which was corroborated in HER2-positive tissue chips and cultured cells. ATF7 gradually decreased with increased tumor stage and low ATF7 was associated with poor prognosis in HER2-positive BRCA patients. ATF7-upregulation inhibited, whereas ATF7-knockdown promoted migration, activity of matrix metalloproteinase 9 (MMP9), MMP2, and uridylyl phosphate adenosine and plasminogen activator inhibitor-1 (PAI-1) expression in HER2-positive cells. HER2 overexpression markedly reduced ATF7 expression in MCF-10A mammary epithelial cells, along with decreased E-cadherin, and increased N-cadherin and migration, which were abrogated by exogenous ATF7 transfection. Mechanistically, HER2 upregulation mediated the decline of ATF7 and activated histone lysine demethylase 1 (LSD1), followed by elevation of histone H3K9 dimethylation (H3K9me2) and H3K4me2. However, the enhanced effects on LSD1 and H3K9me2, excluding H3K4me2, were abrogated by exogenous ATF7. ATF7 was negatively associated with KDM1A (encoding LSD1 protein) expression. CONCLUSIONS: ATF7 may be a useful diagnostic and prognostic marker for metastatic HER2-positive BRCA. The ATF7/LSD1/H3K9me2 axis may be responsible for metastasis in HER2-positive cells.

Research of shRNAmir inhibitory effects towards focal adhesion kinase expression in the treatment of gastric cancer.

Gastric cancer is the fourth most common type of malignant tumor, with a poor prognosis. Focal adhesion kinase (FAK) mediates the crosslink of intracellular signaling networks, playing a key role in cell migration and invasion. The aim of the present study was to investigate the effects of FAK interference on the proliferation ability, invasion and metastasis of gastric cancer cells. The FAK-RNAi lentiviral vector was infected into SGC7901 gastric cancer cells in order to observe the in vivo situations of tumor growth and metastasis before and after the FAK interference. The growth of SGC7901 gastric cancer cells in the interference group was significantly inhibited compared with that of the negative control (P<0.05) and the blank control groups (P<0.05), and the FAK expression significantly decreased (P<0.05). The in vitro invasion and metastasis experiments showed that the cell invasion and metastasis abilities of the interference group significantly decreased when compared with those of the negative control (P<0.05) and blank control groups (P<0.05). In the nude mouse subcutaneous tumor transplantation model, the mean ± standard deviation tumor weight of the interference group (1.474±0.9840 g) was lower than that of the negative control (3.134±0.3299 g) and blank control (2.68±0.12 g) groups (P<0.05). In the nude mice, the liver and peritoneal metastasis rates of the interference group were significantly lower than those of the negative control (P<0.05) and the blank control groups (P<0.05), and the FAK mRNA of the interference group significantly reduced (P<0.05). In conclusion, FAK interference could effectively suppress the proliferation, invasion and metastasis of transfected SGC7901 gastric cancer cells, and could inhibit the growth and distant metastasis of gastric cancer in nude mice.