【Abstract】Objective Stromal cell-derived factor-1(SDF-1, CXCL12) is a member of the CXC subfamily of chemokines which, through its cognate receptor (CXCR4), plays an important role in tumor invasion and metastasis. This study analyzed quantitatively the expression of SDF-1 and its relation with clinicopathologic feature and clinical outcome in human breast cancer.Methods Expression of SDF-1 mRNA in 8 breast cancer cell lines, an endothelial cell line HECV and a fibroblast cell MRC5 was studied by using RT-PCR. In addition, the expression of SDF-1 was investigated at both protein (immunohistochemistry) and mRNA(real-time PCR) levels in a group of human normal mammary(n=32) and tumour tissues(n=120). Results SDF-1 expression was identified in MRC5, MDA-MB435s, MDA-MB436, MCF7 cell lines, breast tumour and normal tissues. Significantly higher level of SDF-1 was seen in lymph node positive than in lymph node negative tumours (399.00±210.00 vs 0.89±0.47), P=0.048. The level of SDF-1 expression in patients who developed local recurrence or metastasis, or patients who died of breast cancer was higher than in patients who were disease free as well, (670.00±346.00 vs 0.83±0.35), P=0.01. It was most notable that level of SDF-1 was significantly correlated with over survival (P=0.01) and incidence free survival (P=0.035, by Cox proportion analysis).Conclusion SDF-1 is a factor that is expressed in both stromal cells and some breast cancer cells. Its level are correlated with lymph node involvement, prognosis and survival in patients with breast cancer. SDF-1 may therefore have a potential prognostic value in breast cancer.
Objective To investigate the effect of steroid receptor coactivator family in initiation, development, treatment and prognosis of breast cancer. Methods The literatures in recent years which have related to the effect of steroid receptor coactivators in breast cancer are reviewed. Results Steroid receptor coactivators are essential for several kinds of steroid hormones binding to steroid receptors, so they are important accessory factors that induce the initiation, development and recurrence of breast cancer, and predictive factors that estimate the prognosis of breast cancer. Conclusion Inhibition of the expression and signaling pathway of steroid receptor coactivators may be effective for breast cancer prevention and treatment.
ObjectiveTo evaluate the diagnostic value of contrast enhanced ultrasound (CEUS) to the sentinel lymph node (SLN) of breast cancer. MethodsSeventy-two operable breast cancer patients with clinically negative axillary lymph node were enrolled.Sulphur hexafluoride microbubbles for injection (SonoVue) was used alone as the tracer agent for the sentinel lymph node biopsy (SLNB), and axillary dissection was performed after the methylene blue location.All SLNs were examined pathologically with HE staining.The SLN diagnosis result of contrast enhanced ultrasound and postoperative pathological examination result were comparative analyzed. ResultsAfter the injection of SonoVue can obtain a clear image of the lymphatic vessels and SLN.The success rate of CEUS imaging was 84.72% (61/72) in this group of 72 patients, and the false negative rate was 12.12% (4/33).The sensitivity and specificity of diagnosis by CEUS was 92.50% (37/40) and 92.59% (50/54), respectively, the diagnostic odds ratio (DOR) was 154.17.By the pathology results as the gold standard, the internal consistency of these two methods was good (Kappa value=0.848, P < 0.01). ConclusionCEUS may be a useful orientation and determination method for SLNs.
Objective To investigate the clinical significance of the amplification of CyclinD1 gene and overexpression of its protein product in breast cancer. Methods Semi-quantitative PCR and immunohistochemical techniques were used to examine the amplification of CyclinD1 gene and overexpression of its protein product in breast cancer, mammary tissues adjacent to the tumor, mammary benign disease and normal mammary tissues. Results The results showed that amplification of CyclinD1 gene was observed in 14 out of 62 (22.6%) breast cancer, the overexpression of its protein product was 48.4% (30/62). Compared with other mammary tissues, these findings were significant. Amplification of CyclinD1 gene and overexpression of its protein were positively associated with histological grade, and there was a b correlation between CyclinD1 protein overexpression and estrogen receptor (progestogen receptor). Conclusion The degree of CyclinD1 protein overexpression is not quite the same as the frequency of the amplification of CyclinD1 gene. It suggests that the overexpresstion of CyclinD1 protein is also attributed to some other mechanisms. Estrogen might stimulate the expression of CyclinD1. The detection of CyclinD1 gene and its protein in breast cancer has some clinical significances.
Objective To observe the outcomes of using different concentrations of arsenic trioxide at varying phases on the breast cancer cell line MCF-7 and to study the mechanism of this effect. Methods The effect of arsenic trioxide on the growth of breast cancer cell line MCF-7 was observed after applying arsenic trioxide of different concentrations （0.5-16 μmol/Ｌ）. The inhibitory effect of arsenic trioxide on the cell proliferation was investigated with 3-(4，5-dimethyl-thizazol-2-yl)-2， 5-diphenyl tetrazolium bromide (MTT) and the induction of arsenic trioxide on cell apoptosis was detected by DNA ladder and terminal deoxynucleotidyl transferase mediated nick end labeling (TUNEL). Results The effect of arsenic trioxide on breast cancer cell line MCF-7 depended on the phase and the dose. The number of cell decreased significantly and there were conspicuously typical morphological changes of apoptosis after the use of arsenic trioxide， including membrane blebbing， chromatin pyknosis, nuclear fragmentation and the formation of apoptotic body. The typical DNA ladders were observed in the MCF-7 cells after 48 h administration of arsenic trioxide at concentrations 1-8 μmol/Ｌ. Significant elevations of apoptosis index at 24 h, 48 h and 72 h were all detected by TUNEL after incubating with 4 μmol/L arsenic trioxide. Conclusion Arsenic trioxide may inhibit the growth of breast cancer cell line MCF-7 significantly by inducing the apoptosis of breast cancer cell.
To investigate the relationship between metallothionein (MT) and prognosis in breast cancer MT expression was determined with immunohistochemical method (SABC). Results: There was a statistically significant association between expression of MT in breast benign and malignant disease (Ｐ＜0.005). The positive rate was 73.8%(62/84) and 15.0%(3/20) in breast cancer and mastofibroma respectively. The positivity of MT was ber in advanced clinical stages than in early clinical stages. There was no association between MT expression and lymph node metastasis. The mortality of the cancer cases with lymph node metastasis having positive MT expression was higher than those with negative MT expression. Conclusion: MT can be taken as a prognostic index of breast cancer.
To evaluate the significance of bcl-2 protein, estrogen receptor (ER), progesterone receptor (PR) and p53 oncogene in invasive breast cancer of ductal and lobular type. Tumor tissues were examined immunohistochemically in paraffin embedded tissues from 125 patients. Results: The invasive ductal breast carcinomas expressed bcl-2 protein significantly less frequently than the lobular type (Ｐ＜0.001). And the expression of bcl-2 protein was significantly correlated with ER, PR (Ｐ＜0.001) and p53 (Ｐ＜0.001), also correlated with primary tumor size and grade. No statistical evidence was found to indicate the relationship between bcl-2 protein expression and anxillary lymph node metastasis. Conclusions: The expression of bcl-2 protein may be regarded as a biological index and may play important role in evaluating the biological characteristics of breast cancer.
At present, breast cancer is most common malignant tumor among female population. The treatment of breast cancer comprises surgery, radiotherapy, neoadjuvant and adjuvant therapy, with surgical as the main treatment approach. Common surgical methods for breast cancer include breast conservation surgery (BCS) and mastectomy. This article reviews the recent researches about the survival of breast cancer patients receiving BCS, the quality of life for patients receiving BCS, the survival of young and elderly patients receiving BCS, BCS after neoadjuvant chemotherapy, BCS for patients with breast cancer susceptibility gene mutation, and BCS for patients with ipsilateral breast tumor recurrence, so as to provide reference for the follow-up work of medical staff.
Objective To explore the causal relationship between breast cancer and rotator cuff injury using bidirectional two-sample Mendelian randomization. Methods Instrumental variables for breast cancer and rotator cuff injury were extracted from published genome-wide association study data. The positive study used breast cancer as the exposure and rotator cuff injury as the outcome, with single nucleotide polymorphisms (SNPs) closely associated with both breast cancer and rotator cuff injury as genetic instrumental variables. The reverse study used rotator cuff injury as the exposure and breast cancer as the outcome, with SNPs closely associated with both breast cancer and rotator cuff injury as genetic instrumental variables. Bidirectional MR analysis was conducted using five models: inverse variance weighted (IVW), simple model, weighted median, weighted model, and MR-Egger to assess the causal relationship between breast cancer and rotator cuff injury. Cochran Q test was used to detect heterogeneity, MR-Egger to detect horizontal pleiotropy, and leave-one-out method for sensitivity analysis to ensure the robustness of the results. Results A total of 51 SNPs closely associated with breast cancer were included in the forward study. The results indicated a positive causal association between breast cancer and an increased risk of rotator cuff injury [IVW: odds ratio=1.08, 95% confidence interval (1.02, 1.12), P=0.014], with no evidence of heterogeneity in the causal relationship between breast cancer and rotator cuff injury (P>0.05). Horizontal pleiotropy test results showed no horizontal pleiotropy in the SNPs (P>0.05). Leave-one-out test results did not detect any SNP with a large impact on the results. In the reverse study, a total of 3 SNPs related to rotator cuff injury were included as instrumental variables. There was no strong evidence that rotator cuff injury had a causal effect on breast cancer incidence [IVW: odds ratio=0.95, 95% confidence interval (0.86, 1.05), P=0.334]. Conclusions There is a potential causal association between breast cancer and rotator cuff injury. Therefore, it is suggested to increase the screening for rotator cuff injury in breast cancer patients.
Objective To investigate the trend of breast cancer treatment and prognosis in 30 years. Methods Total 1 092 patients with breast cancer treated in the Peking Union Medical College Hospital between 1975 and 2006 were reviewed in six time phases for therapy, metastasis, and survival rate. Six time phases were 1975-1980 years, 1985-1986 years, 1990-1991 years, 1995-1996 years, 2000-2001 years and 2005-2006 years. Results Radical operation was the major treatment (68.9%， 91/132) of breast cancer in 1975-1980 and then became less popular until it was totally abandoned after 2001. The number of modified radical operation begun to rise from 1980 and reached its peak in 1995-1996 (94.9%， 146/154). The number of lumpectomy had been increasing since 2000, and that of chemotherapy had been rising since 1985-1986. But there was no apparent change of the percentage of radiotherapy treatment. In 1975-1980, only 0.8% （1/126） patients received endocrine therapy, but in 1990-1991, the ratio was 66.0% （33/50）. The metastasis and recurrence ratio was declining gradually in the 6 time phases (P＜0.05). The 5-year and 10-year disease free survival rates in the groups of 1990-1991, 1995-1996, 2000-2001, and 2005-2006 were apparently higher than those in two earlier groups of 1975-1980 and 1985-1986 (P＜0.05). Conclusion The conclusions of laboratory experiments and clinical trials on breast cancer are critical for improving prognosis.