Serum Long Non-Coding RNAs PVT1, HOTAIR, and NEAT1 as Potential Biomarkers in Egyptian Women with Breast Cancer.

Long non-coding RNAs play an important role in tumor growth, angiogenesis, and metastasis in several types of cancer. However, the clinical significance of using lncRNAs as biomarkers for breast cancer diagnosis and prognosis is still poorly investigated. In this study, we analyzed the serum expression levels of lncRNAs PVT1, HOTAIR, NEAT1, and MALAT1, and their associated proteins, PAI-1, and OPN, in breast cancer patients compared to fibroadenoma patients and healthy subjects. Using quantitative real-time PCR (qRT-PCR), we compared the serum expression levels of the four circulating lncRNAs in patients with breast cancer (n = 50), fibroadenoma (n = 25), and healthy controls (n = 25). The serum levels of PAI-1 and OPN were measured using ELISA. Receiveroperating-characteristic (ROC) analysis and multivariate logistic regression were used to evaluate the diagnostic value of the selected parameters. The serum levels of HOTAIR, PAI-1, and OPN were significantly higher in breast cancer patients compared to controls and fibroadenoma patients. The serum level of PVT1 was significantly higher in breast cancer patients than in the controls, while that of NEAT1 was significantly lower in breast cancer patients compared to controls and fibroadenoma patients. Both ROC and multivariate logistic regression analyses revealed that PAI-1 has the greatest power in discriminating breast cancer from the control, whereas HOTAIR, PAI-1, and OPN have the greatest power in discriminating breast cancer from fibroadenoma patients. In conclusion, our data suggest that the serum levels of PVT1, HOTAIR, NEAT1, PAI-1, and OPN could serve as promising diagnostic biomarkers for breast cancer.

miR-188-5p suppresses cellular proliferation and migration via IL6ST: A potential noninvasive diagnostic biomarker for breast cancer.

Previously, serum miR-188-5p is differentially expressed in breast cancer, but the diagnostic potential of circulating miR-188-5p as well as its regulatory mechanism in breast cancer remain uncertain. Herein, serum miR-188-5p was detected by real-time polymerase chain reaction in patients with breast cancer, breast fibroadenoma, and healthy subjects. Circulating miR-188-5p was abnormally elevated in patients with breast cancer as compared with these other two groups, and was reduced in patients with breast cancer following surgical treatment. Increased serum miR-188-5p corresponded to lymph node metastasis status and TNM stages of breast cancer. A receiver operating characteristic curve analysis of the ability to circulate miR-188-5p to distinguish between patients with breast cancer and either noncancerous patients or patients with breast fibroadenoma yielded corresponding areas under the curve of 0.894 and 8.814. miR-188-5p was downregulated in the highly malignant cancer line MDA-MB-231 relative to the less malignant MCF-7 cells. In vitro, functional analyses conducted via transfecting cells with mimics and inhibitors revealed miR-188-5p to suppress breast cancer cell proliferation and migration, which was mediated by its downstream target IL6ST. Comparison of intracellular and exosomal miR-188-5p levels indicated that miR-188-5p was selectively sorted into exosomes derived from MDA-MB-231 cells rather than those from MCF-7 cells. However, exosomal miR-188-5p levels in the serum of patients with breast cancer were reduced compared to healthy controls and did not differ relative to patients with breast fibroadenoma. In summary, miR-188-5p acts in a tumor-suppressive manner in breast cancer progression and may serve as a noninvasive early diagnostic biomarker and therapeutic target in breast cancer.

Patients With Invasive Ductal Carcinoma Have Reduced Levels of Decorin Expression in Their Breast Tissue Compared to Patients With Fibroadenoma While Plasma Decorin Remains Unchanged.

BACKGROUND: Reduction in the level of tissue decorin is a hallmark of many types of cancer including breast carcinoma. However, reduced decorin expression has also been reported in several types of benign tumors to the extent that it has been proposed as a tissue marker to differentiate malignant from benign tumors. The aim of this study was to investigate the potential role of plasma decorin to distinguish breast cancer from fibroadenoma, the second most common type of benign tumor, after fibrocystic disease. METHODS: From 35 patients recruited in this study, 24 were affected with invasive ductal carcinoma, either grade II (n = 14) or grade III (n = 10). The other 11 patients had fibroadenoma lesions in their breasts. Tissue decorin mRNA and protein levels were assessed with real-time qPCR and Immunohistochemical analysis. ELISA was employed to measure plasma levels of decorin. RESULTS: The mean plasma decorin in cancer patients was measured to be 5.42 ± 1.83 ng/mL while fibroadenoma patients had an average of 4.22 ± 1.17 ng/mL decorin in their plasma. The difference was not significant. However, the mean expression level of decorin mRNA calculated by the 2-ΔΔCt method was 5.6-fold lower in the biopsied tissue specimens of IDC patients versus fibroadenoma, as expected. Consistent reduction in protein abundance was observed in the studied tissue sections. CONCLUSION: We have shown that tissue decorin is a reliable marker, unaffected by patient disease stage, to differentiate IDC from fibroadenoma. However, plasma decorin does not seem to have diagnostic value in this regard.

Calponin-h2: a potential serum marker for the early detection of human breast cancer?

Early diagnosis is the key for the successful treatment of breast cancer. A serum marker for the early detection of breast cancer could significantly reduce breast cancer morbidity and mortality by bringing the time of diagnosis at an earlier and therefore still curable stage. So far, no biomarker for the early detection is available for the clinical routine. The aim of the present study was to evaluate the use of calponin-h2 as a blood-based biomarker for the early diagnosis of this disease. Using two monoclonal antibodies against calponin-h2, we developed a sandwich ELISA to analyze the serum levels of calponin-h2. In order to evaluate the diagnostic potential of this biomarker, patients with breast cancer (n = 76), benign diseases of the breast (n = 51) and healthy females (n = 24) were analyzed. Serum levels above 10 ng/ml were only observed in patients with breast cancer (n = 8; 10.5%). Further large-scale studies and preanalytic evaluations are necessary to clarify the definite role of calponin-h2 as a biomarker in breast cancer management.

Levels of serum 25-hydroxy-vitamin d in benign and malignant breast masses.

BACKGROUND: The true association between breast cancer and vitamin D is currently under investigation. We compared serum 25-hydroxy-vitamin D levels in women with benign and malignant breast masses and controls. MATERIALS AND METHODS: Levels of vitamin D were measured by electrochemiluminescense. Serum levels >35 ng/ml, 25-35 ng/ml, 12.5-25 ng/ml and <12.5 ng/ml were considered as normal, mild, moderate and severe vitamin D deficiency, respectively. RESULTS: Overall, 364 women were included in the control, 172 in the benign and 136 in the malignant groups. The median serum vitamin D level was significantly lower in breast cancers than controls. Levels were also lower in malignant than benign cases and in benign cases than controls although statistically non-significant. CONCLUSIONS: Multinomial logistic regression analysis showed that severe vitamin D deficiency causes a three-fold increase in the risk of breast cancer while this was not the case for moderate and mild deficiency.

Evaluation of histidine-rich glycoprotein tissue RNA and serum protein as novel markers for breast cancer.

Advances in the field of breast cancer (BC) biomarkers discovery facilitate diagnosis and treatment of BC in its pre-invasive state. While the genetic tissue markers are making significant advances in understanding the molecular basis of BC, serum has long been considered a rich source for biomarkers. So, integrated genomic and proteomic strategies play a huge role in the analytical validation of BC biomarkers and represent a true milestone in the areas of diagnostics and personalized medicine. This study included 60 cases (BC), 30 patients with fibroadenoma and 30 healthy women. Histidine-rich glycoprotein RNA (HRG) tissue expression was analyzed through gene expression-based outcome for breast cancer online algorithm (GOBO) bioinformatic analysis. To confirm our informatics analysis, HRG RNA was detected in breast tissue samples by RT-PCR, and HRG serum protein was estimated by ELISA. GOBO analysis revealed increased HRG RNA expression in all subtypes of BC with relative higher expression in basal subtype and grade 2. We confirmed these findings by HRG tissue RNA with 71.7% sensitivity and 93.3% specificity. HRG serum protein was 86.7% sensitivity and 80% specificity. HRG tissue RNA and serum protein could be considered as promising novel markers for prediction of BC prognosis.

Impact of breast cancer surgery on angiogenesis circulating biomarkers: a prospective longitudinal study.

BACKGROUND: Debate about the potential effects that surgery might have on cancer cells dormancy and angiogenesis prompted us to investigate the impact of breast surgery on circulating angiogenesis modulating gene transcripts and proteins. METHODS: Blood samples from 10 female patients diagnosed with breast cancer and 6 with fibroadenoma were collected before surgery and post-operatively on days 3 and 7 (breast cancer patients only). A set of 84 angiogenesis-associated transcripts were assessed using quantitative PCR arrays, and circulating protein levels (vascular endothelial growth factor A (VEGFA), IL8 and fibroblast growth factor 2 (FGF2) were measured using ELISA in the same samples. The results were investigated against clinicopathological data and patient outcome. RESULTS: Plasma levels of VEGFA and IL8 after surgery were significantly elevated in the breast cancer group compared to the control group (P = 0.038 and P = 0.021, respectively). In the cohort of breast cancer patients, VEGFA increased on day 3 (P = 0.038) and declined on day 7 (P= 0.017), while IL8 did not change on day 3 but showed a significant decline on day 7 (P = 0.02). FGF2 levels did not change significantly over time. Regarding gene transcripts, we detected upregulation of a significant number of angiogenesis-specific genes in patients with breast cancer versus controls: sphingosine kinase 1(SPHK1), epidermal growth factor (EGF), vascular endothelial growth factor C (VEGFC), neuropilin 1 (NRP1), fibroblast growth factor (FGF1), laminin alpha 5 (LAMA5), collagen type IV alpha 3 (COL4A3), IL8, ephrin B2 (EFNB2), ephrin A3 (EFNA3), tyrosine endothelial kinase (TEK), integrin beta 3 (ITGB3), AKT1, thrombospondin 1 (THBS1), chemokine (C-C motif) ligand 11 (CCL11) and TIMP metallopeptidase inhibitor 3 (TIMP3). Surgery induced an altered expression in several keygenes in breast cancer patients. We identified an upregulation of COL4A3 and downregulation of chemokine (C-X-C motif) ligand 9 (CXCL9), EGF, FGF1, Kinase insert domain receptor (KDR), Placental growth factor (PGF), TIMP3 and VEGFC. CONCLUSION: Breast cancer patients have a different expression profile of circulating angiogenesis biomarkers compared to patients with fibroadenoma. Moreover, mastectomy promotes a transient increase of VEGFA and a shift in the expression patterns of a broad panel of angiogenesis-related circulating gene transcripts.

Hematopoietic cytokines as tumor markers in breast malignancies. A multivariate analysis with ROC curve in breast cancer patients.

PURPOSE: Plasma levels of selected hematopoietic cytokines: interleukin 3 ( IL-3), stem cell factor (SCF), granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF) and macrophage colony-stimulating factor (M-CSF), and the tumor marker carcinoma antigen 15-3 (CA 15-3) in breast cancer (BC) patients were investigated and compared to control groups: benign breast tumor patients and healthy subjects. MATERIAL/METHODS: Cytokine levels were determined by ELISA, CA 15-3 - using the CMIA method. RESULTS: A significant differences in the concentration of cytokines (with the exception of IL-3) and CA15-3 between the groups of BC patients, benign breast tumor patients and the healthy controls have been demonstrated. M-CSF has demonstrated higher or equal to CA 15-3 values of diagnostic sensitivity, specificity and the predictive values of positive and negative test results. The M-CSF area under the ROC curve (AUC) was the largest from all the cytokines tested and marginally lower than the AUC of CA 15-3. CONCLUSION: These findings suggest the usefulness of M-CSF in diagnosing breast cancer, especially when discriminating between cancer and non-carcinoma lesions.

Usefulness of serum CA-15.3 in the management of benign breast lesion.

Benign breast lesion is an important risk factor for breast cancer and elevated CA-15.3 in serum is a well established marker of breast cancer. Core-needle biopsy is now the method of choice to sample non-palpable mammographic abnormality and as well as clinically palpable lesion. To asses relationship of serum CA-15.3 with different histologic entities of benign breast lesion and usefulness of this marker in predicting breast cancer in this high risk group, a study was conducted among 140 patients who had a diagnosis of benign breast lesion and malignancy following fine needle aspiration cytology (FNAC) at department of surgery, Medical College, Kolkata between 2007 and 2009. We prospectively estimated serum CA-15.3 level in all patients. Different histologic entities of benign breast lesion, who showed serum CA-15.3 level >30U/ml underwent tru-cut biopsy to detect malignancy. Of 140 patients studied, 50 were stamped as malignancy and 90 as benign after FNAC of which 20 patients had fibroadenoma, 25 had fibro-adenoma with fibrocystic disease, 20 had fibrocystic disease with epitheliosis and 25 had fibrocystic disease with atypia. All breast cancer patients and 10 each from fibro-adenoma with fibrocystic disease, fibrocystic disease with epitheliosis and fibrocystic disease with atypia had serum CA -15.3 level>30U/ml. Thirty patients with benign breast lesion who had raised CA-15.3 underwent core-needle biopsy. Fifteen patients were detected to have intraductal carcinoma, mostly with fibrocystic disease with atypia. Clinical applicability of serum CA-15.3 to detect breast cancer should be strongly considered in management of patients with benign breast lesion and tru-cut biopsy than FNAC be done before benign breast lesion being stamped as benign. Biopsy results that are not concordant with the targeted lesion require surgical biopsy.

Clinical MR mammography: impact of hormonal status on background enhancement and diagnostic accuracy.

PURPOSE: Hormonal stimulation can induce background enhancement (BE) in MR mammography (MRM). This fact has been assumed to decrease the accuracy of MRM. Consequently, this report investigates: 1. The prevalence of BE in postmenopausal vs. premenopausal women in correlation to hormonal cycle phase (CP). 2. The impact of hormonal status (HS) and BE on diagnostic accuracy. MATERIALS AND METHODS: Consecutive patients over 22 months with complete HS information (week of CP or postmenopausal) were included in this prospective investigation. Exclusion criteria were any hormonal therapy, hysterectomy as well as cancer proven by biopsy. The standard of reference was histopathology. All MRM scans were acquired using the same protocol (1.5 T, dynamic T 1w GRE after 0.1 mmol/kg bw Gd-DTPA i. v.). Two radiologists rated all examinations in consensus according to BI-RADS. BE was defined as: 0 = missing, 1 = moderate, 2 = distinct. RESULTS: 224 patients (150 postmenopausal, 74 premenopausal, 45 in the second week of CP) were included in this study (83 benign and 141 malignant findings). BE was more frequent in premenopausal women (p = 0.006), but did not differ between CP (p = 0.460). Neither HS nor BE had a significant impact on the diagnostic parameters of MRM (p ≥ 0.375). However, regarding BE, the relative number of false positive (FP) findings was highest (5 / 10; 50 %) in the distinct BE group. Regarding HS, 17 % more FP findings were observed in premenopausal women examined outside the second week of CP. CONCLUSION: In premenopausal women, HS leads to increased BE of breast tissue, independent of CP. Distinct BE and less pronounced, non-optimal CP may lead to an increased number of false positive findings.

[The diagnostic value of RNA oncomarkers in evaluation of malignant breast tumors].

The levels of the RNA oncomarkers, telomerase (hTERT), cytokeratin-19 (CK-19) and mammaglobin (MAM) have been investigated in capillary blood of female patients with mammary ductal carcinoma. The study revealed overexpression of all three factors in patients with this pathology. This overexpression was not found in healthy donors and female patients with mammary fibroadenoma. Levels of the RNA oncomarkers return to the normal level within 10 days after successful tumor resection. These results have been used for the development of diagnostic kits, which may be applicable for differential diagnostics, screening and postoperation monitoring of patients with malignant breast tumors

Hepatocyte growth factor in Egyptian females with breast benign lumps and cancers.

BACKGROUND: Hepatocyte growth factor (HGF) also known as scatter factor (SF) and its receptor c-met play important roles in mammary differentiation and have been implicated in mammary carcinogenesis. OBJECTIVE: Estimation of the plasma level of HGF in females with benign breast lumps or breast carcinomas and correlating levels with important prognostic parameters. SUBJECTS: Sixty eight adult premenopausal females were divided into control group of fifteen healthy volunteers and fifty-three patients subdivided into fifteen with benign breast lumps and thirty-eight with breast carcinomas. METHODS: A thorough clinical examination, plain chest x-rays, ultrasonography of the abdomen and pelvis, pre- operative fine needle aspiration cytology, estimation of fasting serum glucose, urea, creatinine and uric acid levels, alanine aminotransferase activities, C-reactive protein, HGF level and histopathological examination of the breast masses were performed. RESULTS: Significant increase in HGF levels was found in patients with benign breast lumps and in breast cancer patients when each was compared to controls and when cancer patients were compared to the benign breast lumps group. CONCLUSION: The serum level of HGF is an independent prognostic indicator for breast cancer.

[Application of serum proteomic mass spectrum analysis in breast cancer].

OBJECTIVE: To analyze the characteristics of serum proteins mass spectra in healthy controls, benign breast tumors, and CA15-3 negative or CA15-3 positive breast cancer patients by surface enhanced laser desorption ionization time of flight mass spectrometry (SELDI-TOF-MS). METHODS: Tissue samples of 113 cases of breast cancer (93 case of CA15-3 negative, 20 case of CA15-3 positive), 103 cases of benign breast tumor and 92 cases of healthy controls were examined and analyzed by SELDI and protein chip (CM10) techniques. Biomarker Pattern Software (BPS) was used to detect the protein peaks significantly different between them and establish a diagnostic pattern which was further evaluated by a blind test. RESULTS: Twelve significantly different protein peaks were found in serum samples between breast cancer patients and healthy controls. Eleven significantly different peaks were found between benign breast tumor patients and healthy controls. By combined analysis of those three different protein mass spectra, the peak 15 952 was found to be significantly different between breast cancer group and healthy controls, and the peak 7985 was significantly different among breast cancer group, benign breast tumor group and health controls. The blind test with the differential proteins for the serum samples of 93 cases of CA15-3 negative breast cancer and 36 cases of benign breast tumors showed that the sensitivity was 80.6% and specificity was 91.7%. The blind test in 20 cases of CA15-3 positive breast cancer and 36 cases of benign breast tumors showed that the sensitivity was 75.0% and specificity was 91.7%. Four significantly different protein peaks were found between the benign breast tumor patients and CA15-3 negative breast cancer patients. No significantly different protein were found between CA15-3 negative and CA15-3 positive patients. CONCLUSION: Significantly different protein peaks can be screened out in breast cancer, benign breast tumor patients and healthy controls by SELDI-TOF-MS analysis.

[Low-molecular DNA in blood plasma and spinal fluid of cancer patients].

Enhanced preoperative levels of low-molecular DNA in blood plasma and in cerebrospinal fluid were established in cancer patients. They rose even higher after surgery due to stress. Possible mechanisms are discussed.

Biomarkers of dietary exposure are associated with lower risk of breast fibroadenomas in Chinese women.

Fibroadenomas are the most common benign breast condition among women and account for up to 50% of all breast biopsies being performed. Although considered a benign condition, fibroadenomas utilize substantial resources for management and treatment to rule out potential malignancies. Dietary factors may influence benign fibrocystic breast conditions, but little is known of their association with fibroadenomas. We examined possible associations between a broad spectrum of circulating biomarkers of dietary intake and risk of fibroadenomas. Participants were women in a breast self-examination trial in Shanghai, China who were diagnosed with fibroadenomas (n = 258) and 1035 controls. Conditional logistic regression was used to estimate adjusted odds ratios (OR) and 95% CI. Isoflavone concentrations were inversely associated with risk of fibroadenomas. Adjusted OR (95% CI) for the highest versus the lowest quartile of plasma concentration were 0.36 (0.16-0.79; P-trend < 0.001) for daidzein and 0.39 (0.19-0.84; P-trend = 0.010) for genistein. We also observed inverse associations between higher percentages of the RBC (n-3) fatty acids, eicosapentaenoic acid (EPA) ([0.38 (0.19-0.77); P-trend = 0.007] and docosapentaenoic acid (DPA) [0.32 (0.15-0.70); P-trend = 0.024], and fibroadenoma risk. Circulating concentrations of carotenoids, vitamin C, retinol, and ferritin were not associated with fibroadenoma risk. The inverse associations between plasma isoflavone concentrations and RBC EPA and DPA and fibroadenoma risk suggest that higher intakes of soy foods and fatty fish may lower the risk of fibroadenomas.

DNA oxidation and antioxidant status in breast cancer.

PURPOSE: : Oxidant/antioxidant balance has been suggested as an important factor for initiation and progression of cancer. The objective of this study was to determine 8-hydroxydeoxyguanosine (8-OHdG) level as a marker of oxidative DNA damage, glutathione peroxidase (G-Px), and superoxide dismutase (SOD) activities as antioxidant activity, in sera from women with breast cancer. METHODS: : Forty-nine patients with malign breast tumor were included in the study. Blood samples were collected before the surgical operation. Serum level of 8-OHdG was measured with a competitive enzyme-linked immunusorbent assay kit, SOD, and G-Px activities were measured by spectrophotometric kits. RESULTS: : 8-Hydroxydeoxyguanosine level and SOD activity were found to be increased in breast cancer group as compared with control group. Glutathione peroxidase activity in the breast cancer group was lower than those in the control group. The ratio of 8-OHdG/G-Px in breast cancer patients was found to be higher than those in the controls. There were correlations between 8-OHdG and CA19-9 (r = 0.77; P < 0.01); age and G-Px (r = -0.84; P < 0.05) in the breast cancer group. CONCLUSIONS: : Data show that serum levels of 8-OHdG and SOD activities are higher in patients with breast cancer. Glutathione peroxidase activity is lower in the breast cancer group. Increased ratio of 8-OHdG/G-Px in breast cancer patients is the evidence for impaired oxidant/ antioxidant balance in breast cancer.

Serum and tissue LDH levels in patients with breast/gynaecological cancer and benign diseases.

BACKGROUND: Lactate dehydrogenase A (LDHA) is involved in anaerobic glycolysis. In cancer patients, serum total lactate dehydrogenase (LDH) levels are often increased, and the gene for one of its isoenzymes, LDHA, is up-regulated. These features have been linked to poor prognosis in several studies. METHODS: We investigated comparatively the total serum LDH activity and tissue isoenzyme LDH5 and hypoxia-inducible factor 1alpha (HIF1alpha) levels in patients with breast (n = 18) and gynaecological (n = 23) malignancies and benign diseases (n =54). RESULTS: The serum LDH levels were significantly higher in patients with endometrial adenocarcinoma (349 +/- 100 IU/l) and ovarian cystadenocarcinomas (383 +/- 116 IU/l) compared to healthy controls (256 +/- 68 IU/l) (p values 0.01 and 0.006, respectively). This difference did not reach significance in patients with breast cancer (328 +/- 169 IU/l; p = 0.17)). Uterine leiomyoma patients showed intermediate LDH levels (310 +/- 81 IU/l), while patients with breast fibroadenomas and ovarian cystadenomas had LDH serum levels close to carcinomas (308 +/- 60 and 348 +/- 135 IU/l, respectively). LDH5 isoenzyme was strongly expressed in cancer cells, exhibiting a mixed cytoplasmic/nuclear subcellular pattern. Interestingly, a high LDH5 content in tissue sections was not invariably accompanied by high LDH serum levels. High HIF1alpha tissue expression was linked to high tissue LDH5 expression. CONCLUSION: Serum and tissue LDH is up-regulated in gynaecologic and breast malignancies and in a subset of benign conditions such as fibro- and cystadenomas. The release of LDH, however, in the bloodstream is partly related to the LDHA gene up-regulation.

[Lactate dehydrogenase, adenosine deaminase and thymidine phosphorylase activity of blood and tissues in breast cancer].

Lactate dehydrogenase (LDH), adenosine deaminase and thymidine phosphorylase activity was analyzed in the blood serum, primary tumor and adjacent uninvolved breast tissues from 49 women with adenocarcinoma and from 10 ones with benign adenofibroma. The LDH activity was increased in both cancerous and adjacent tissues. Serum LDH level reflects cell membrane alterations not only in the tumor node cells but also to a greater extent--in the surrounding unmalignant tissues. The discovered changes in nucleosides catabolic enzyme's activity in patients with breast cancer are correlated with LDH activity and its level in the blood serum.

[Relationship between serum VEGF level and VEGF, COX-2 and MVD expression in breast cancer tissues].

OBJECTIVE: To investigate the relationship between serum VEGF (sVEGF) level and VEGF, COX-2 and MVD expression in breast cancer, and to discuss their role in angiogensis of breast cancer. METHODS: sVEGF level was detected by ELISA in 68 preoperative breast cancer, 35 benign breast disease and 20 healthy women. The expression of VEGF, COX-2 and MVD was detected by immunohistochemical method in tissues of breast cancer and breast benign diseases, and to analyze the relationship of sVEGF, VEGF, COX-2 and MVD. RESULTS: (1) sVEGF level in preoperative breast cancers was 306.51 pg/ml (interquartile range from 190.44 to 442.04 pg/ml), in benign diseases was 150.82 pg/ml (interquartile range from 82.36 to 212.34 pg/ml), and in healthy control was 105.93 pg/ml (interquartile range from 78.54 to 157.77 pg/ml). The sVEGF level of preoperative breast cancer group was significantly higher than that of breast benign disease group and healthy women (P = 0.001). (2) The VEGF expression positive rate in breast cancer (67.65%) was significantly higher than that in breast benign disease (44.12%) (P = 0.015). The COX-2 expression positive rate in breast cancer (42.86%) was significantly higher than that in breast benign disease (11.43%) (P = 0.002). (3) the COX-2 expression positive rate in sVEGF high level patients (56.00%) was significantly higher than that in sVEGF normal level patients (11.11%) (P = 0.024), and MVD in sVEGF high level patients (27.32 +/- 3.40) was also higher than that in sVEGF normal level patients (15.31 +/- 6.16) (P = 0.011). (4) The sVEGF level (322.09 +/- 79.31) of 68 breast cancer patients whose VEGF was positive in breast cancer tissues was significantly higher than that in VEGF negative group (222.47 +/- 73.53) (P = 0.017). (5) The COX-2 expression positive rate in VEGF positive expression group (65.21%) was significantly higher than that in VEGF negative expression group (18.18%) (P = 0.017). The MVD expression in COX-2 positive expression group (22.94 +/- 5.51) was significantly higher than that in COX-2 negative expression group (10.30 +/- 4.42) (P = 0.027). CONCLUSION: sVEGF level in breast cancer is significantly higher than that in breast benign disease and healthy women, and is correlated with the expression of COX-2 and MVD in breast cancer tissues.