Objective To study the relationship between metalloproteinases (MMPs) and breast cancer. Methods The literature in recent years on the relationship between the expression of MMPs and breast cancer was reviewed. Results The balance between MMPs and tissue inhibitors of metalloproteinases (TIMPs) is keeping normally kept in human body. Many of the studies showed that the expression of MMPs is increased in breast cancer. Conclusion The growth, invasion and metastasis of breast cancer is closely related with the increased expression of MMPs. This suggests that MMPs is a valuable prognostic marker and TIMPs would be a novel drug against 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.
Objective To systematically review the association between menstrual condition and the risk of breast cancer. Methods We searched The Cochrane Library (Issue 4, 2016), PubMed, EMbase, CNKI, WanFang Data, VIP and ScienceDirect databases from inception to June 1st 2016 to collect case-control studies about the association between menstrual condition and breast cancer. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Then, meta-analysis was performed using Stata12.0 software. Results Eighty-three studies involving 48 811 breast cancer patients and 57 268 controls were finally included. The results of meta-analysis showed that breast cancer was associated with age at menarche≤13 years old (OR=1.17, 95%CI 1.12 to 1.24) and irregular menstruation (OR=1.98, 95%CI 1.62 to 2.41), but was not associated with history of dysmenorrhea, cycle time≥30 days and period of time>7 days. Further subgroup analysis showed that the sample size was one of the main source of heterogeneity for history of dysmenorrheal analysis, and breast cancer was associated with the history of dysmenorrhea after removing small-sampled studies (OR=1.47, 95%CI 1.36 to 1.59). The association between breast cancer and age at menarche≤13 years old, irregular menstruation was statistically significant in community control, but not in hospital control. The association between breast cancer and age at menarche≤13 years old, irregular menstruation were statistically significant both in Chinese and foreign population. Conclusion Early age at menarche, irregular menstruation and history of dysmenorrhea may be risk factors of breast cancer. Due to the limitation of quality and quanity of included studies, the above conclusions need more researches to verify.
Objective To compare the long-term outcome between breast-conserving therapy with mastectomy therapy for early stage invasive breast cancer through a Meta analysis of the randomized controlled trials published worldwide. Methods Cochrane systematic evaluation was used to search through Cochrane libraries of clinical comparative trials, PubMed, Embase, Cancer Lit, and so on. The quality of literatures was independently evaluated and cross-checked by two evaluators, indicators for assessment including death number at the end of follow-up, locoregional and total recurrence. The results were analyzed with RevMan 4.2.2 software. Results Six articles were involved in the Meta analysis with total 3 933 patients. No statistical difference was found in the death at the end of follow-up between breast-conserving therapy group and mastectomy therapy group (OR=1.05, 95% CI=0.93—1.19， P=0.45). Locoregional and total recurrence rate of breast-conserving therapy group were statistical higher than those in mastectomy therapy group (OR=1.64, 95% CI: 1.10—2.44， P=0.01； OR=1.42, 95% CI: 1.22—1.64， Plt;0.01). Conclusions Breast-conserving therapy and mastectomy therapy have comparable effects on mortality in patient with early stage invasive breast cancer, even after long-term follow up. However, breast-conserving therapy is associated with significantly greater risk of locoregional recurrence.
Breast cancer is one of the most common malignant tumors in women. The systematic therapy of breast cancer may affect the endometrium and ovarian function, such as abnormal endometrial hyperplasia and abnormal uterine bleeding caused by ovulation disorders. If we do not consider the patients suffering from breast cancer, we can use progesterone drugs to stop bleeding, regulate menstruation, and protect the endometrium. But there is no consistent conclusion on the safety of progesterone drugs in breast cancer patients. This article reviews the security of progesterone drugs in breast cancer survivors from the perspective of basic and clinical research. At present, whether the use of progesterone drugs in breast cancer survivors increases the risk of disease may be related to the type, dosage, and method of use of progesterone drugs. At the same time, it is also related to the type of breast cancer the patient has. Based on the available data, it is safe to use natural progesterone or dydrogesterone for the short term in patients with breast cancer. More studies are needed to evaluate other approaches.
To investigate the changes of tenascin (TN) expression during the course of canceration through atypical hyperplasia of breast epithelia. The SP immunohistochemical method was used to study TN expresson in 50 different breast tissues. Results: There was no TN expression in normal breast and grade Ⅰ hyperplasia; immunostaining of TN was detected in 2 cases with grade Ⅱ atypical hyperplasia; the expression of TN in grade Ⅲ atypical hyperplasia (80%) and infiltrating ductal breast cancer (90%) was significantly higher than that in grade Ⅱ atypical hyperplasia (20%); and immunostaining of TN was detected in part of the cancer cells. Conclusion: These results suggest that TN expression in the stroma of serious atypical hyperplasia may play a role in limiting the outgrowth of hyperplastic epithelia.
ObjectiveTo explore the expression of programmed cell death 4 (PDCD4) in different subtype of breast cancer and its relationship to prognosis. MethodsThree hundred and thirty-eight patients with breast cancer from January 2007 to December 2009 in this hospital were collected. All these patients were categorized into three subtypes which was luminal, HER-2 positive, and triple negative according to the results of immunohistochemical stain. SP immunohistochemistry was used to detect the expression of PDCD4 in the different subtype of breast cancer. Kaplan-Meier and Cox proportional hazards model was used to analyze the prognosis. Results①The positive rate of PDCD4 expression was 73.37%(146/199), 30.16%(19/63), and 35.53%(27/76) in the luminal, HER-2 positive, and triple negative breast cancer, respectively. The expression of PDCD4 was downregulated especially in the HER-2 positive and triple negative breast cancer(χ2=38.315, P=0.000; χ2=33.746, P=0.000) as compared with the luminal breast cancer. 2 The disease free survival and overall survival rates in the PDCD4 positive patients were significantly higher than those in the PDCD4 negative patients(P < 0.05) despite the subtypes.③Cox model revealed that T staging, N staging, and PDCD4 were the independent prognostic factors for disease free survival and that histological grade, T staging, N staging, and PDCD4 were the independent prognostic factors for overall survival. ConclusionsPDCD4 expression is downregulated in all subtypes of breast cancer especially in HER-2 positive and triple negative breast cancer, and the loss of PDCD4 expression is correlated to poor prognosis. PDCD4 is an independent prognostic factor of breast cancer.
【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 detect the expressions of CK5/6 and Ki-67 in breast cancer， and explore the clinical significance. Methods The expressions of CK5/6 and Ki-67 were detected by immunohistochemistry in 162 cases of breast cancer . The correlation between CK5/6 expression and Ki-67 expression and the relationship of the expressions of two factors to the clinicopathologic factors were analyzed. Results There were 12 cases of the triple negative breast cancer 〔negative estrogen receptor （ER）， negative progesterone receptor （PR）， and negative Her-2〕 in 162 patients with breast cancer. The positive rates of CK5/6 and Ki-67 in the breast cancer tissues were 30.9% （50/162） and 65.4% （106/162），respectively. The positive rates of CK5/6 and Ki-67 in the patients with triple negative breast cancer were significantly higher than those of non-triple negative breast cancer 〔CK5/6：75.0% （9/12） versus 27.3% （41/150）， χ2=11.837， P=0.001；Ki-67：100% （12/12） versus 62.7% （94/150）， χ2=6.847， P=0.009〕. The expressions of CK5/6 and Ki-67 in the breast cancer tissues were not associated with age （P＞0.05）， but they were associated with histology grade （P＜0.05）. The expression of CK5/6 wasn’t associated with tumor size and lymph node status （P＞0.05）， but the expression of Ki-67 was associated with them （P＜0.05）. The expression of CK5/6 in the breast cancer tissue had a positive correlation with the expression of Ki-67 in the breast cancer tissue （rs=0.271， P=0.000）. There were 64 cases when the expression of Ki-67 was （＋＋） and （＋＋＋）， the positive rate of CK5/6 was 43.8% （28/64） and it was significantly higher than that when the expression of Ki-67 was （-） and （＋） 〔22.4% （22/98）， χ2=8.233， P=0.004〕. The positive expressions of CK5/6 and Ki-67 in the breast cancer tissues were negatively correlated with the expressions of ER and PR （CK5/6 and ER：rs=-0.446， P=0.000；CK5/6 and PR：rs=-0.370， P=0.000；Ki-67 and ER：rs=-0.518， P=0.000；Ki-67 and PR：rs=-0.515， P=0.000）. The positive expressions of CK5/6 and Ki-67 in the breast cancer tissue were not correlated with the Her-2 expression （CK5/6 and Her-2：rs=0.105， P=0.183；Ki-67 and Her-2：rs=0.068， P=0.393）. Conclusion The expressions of CK5/6 and Ki67 not only can evaluate the basic rules of breast cancer from origin and development， but also they are beneficial to choose the chemotherapy of different patients.
Objective To study the expression and significance of CCR chemokine receptor-7 (CCR7) protein and vascular endothelial growth factor-D (VEGF-D) protein in the progression of breast cancer, including normal breast tissue, slight and moderate atypical hyperplasia, severe atypical hyperplasia and intraductal carcinoma in situ, as well as invasive ductal carcinoma. Methods Immunohistochemistry was used to detect the expression of CCR7 and VEGF-D protein in the nomal breast tissue (n=20), slight and moderate ductal atypical hyperplasia tissue (n=20), severe atypical hyperplasia and intraductal carcinoma in situ tissue, as well as invasive ductal breast carcinoma tissue (n=73). In addition, the D2-40 staining was also used to determine lymphatic microvessel density (LMVD). Meanwhile, the relationship between the expression of the two kinds of protein and clinicopathological factors/LMVD was analyzed by statistical analysis in breast cancer, and the correlation between expression of CCR7 protein and expression of VEGF-D protein was analyzed too. Results ①The positive rates of CCR7 protein (χ 2 =23.905，P<0.050) and VEGF-D protein (χ 2 =22.349，P<0.050) were gradually increased in the normal breast tissue group 〔CCR7 protein: 0 (0/20), VEGF-D protein: 5.0% (1/20)〕, slight and moderate atypical hyperplasia group 〔CCR7 protein: 5.0% (1/20), VEGF-D protein: 20.0% (4/20)〕, severe atypical hyperplasia and intraductal carcinoma in situ group 〔CCR7 protein: 30.0% (6/20), VEGF-D protein: 40.0% (8/20)〕, and invasive ductal carcinoma group 〔CCR7 protein: 47.9% (35/73), VEGF-D protein: 57.5% (42/73)〕. ②The LMVD value gradually increased in normal breast tissue group (2.00±1.02), slight and moderate atypical hyperplasia group (6.70± 3.48), severe atypical hyperplasia and intraductal carcinoma in situ group (9.01±2.13), as well as invasive ductal carcinoma group (16.32±4.07), there was significant difference between any 2 groups (P<0.050). ③The expressions of CCR7 protein and VEGF-D protein were correlated with clinical staging, histological grading, lymph node metastasis, and expression of human epidermal growth factor receptor-2 (HER-2) protein in patients with breast cancer (P<0.050), the higher positive rates of CCR7 and VEGF-D protein occurred in patients with higher histological grading, later clinical staging of Ⅲ+Ⅳ (compared with staging of Ⅰ+Ⅱ), lymph node metastasis (compared with no lymph node metastasis), and positive expression of HER-2 protein (compared with negative expression of HER-2 protein). The result indicated that LMVD value was related with expression of VEGF-D protein (r=0.623, P<0.010) in patients with breast cancer, but there was no correlation with expression of CCR7 protein (r=-0.303, P>0.050). Furthermore, there was weak positive correlation between expression of CCR7 protein and expression of VEGF-D protein in breast cancer (r=0.112, P<0.050). Conclusion The results strongly suggest that the expression levels of the VEGF-D protein and CCR7 protein indicate the potential of translation some extent, and they play an important role in the progression of breast cancer.