Levels In Breast Cancer Patients Research Articles

Serum HER2 Level Measured by Dot Blot: A Valid and Inexpensive Assay for Monitoring Breast Cancer Progression

Human epidermal growth factor receptor 2 (HER2) is one of the most important prognostic and predictive factors for breast cancer patients. Recently, serum HER2 ECD level of patients detected by enzyme-linked immunoabsorbent assay (ELISA) has been shown to predict tumor HER2 status and reveal its association with tumor progression, recurrence and poor prognosis. In this study, we established a new method, dot blot assay, to measure the serum HER2 level in breast cancer patients and further to evaluate the clinical value for monitoring breast cancer progression. We found that the serum HER2 level measured by dot blot assay was significantly correlated with tissue HER2 status in breast cancer patients (P = 0.001), and also significantly correlated with HER2 level measured by ELISA (P = 1.06×10−11). Compared with ELISA method, the specificity and sensitivity of dot blot assay were 95.3% and 65.0%, respectively. The serum HER2 levels of patients with grade III or ER-negative were higher than those with grade I–II (P = 0.004) and ER-positive (P = 0.033), respectively. Therefore, the novel dot blot method to detect serum HER2 level is a valid and inexpensive assay with potential application in monitoring breast cancer progression in clinical situations.

Topical Testosterone for Breast Cancer Patients with Vaginal Atrophy Related to Aromatase Inhibitors: A Phase I/II Study

Controversy exists about whether vaginal estrogens interfere with the efficacy of aromatase inhibitors (AIs) in breast cancer patients. With the greater incidence of vaginal atrophy in patients on AIs, a safe and effective nonestrogen therapy is necessary. We hypothesized that vaginal testosterone cream could safely treat vaginal atrophy in women on AIs. Twenty-one postmenopausal breast cancer patients on AIs with symptoms of vaginal atrophy were treated with testosterone cream applied to the vaginal epithelium daily for 28 days. Ten women received a dose of 300 μg, 10 received 150 μg, and one was not evaluable. Estradiol levels, testosterone levels, symptoms of vaginal atrophy, and gynecologic examinations with pH and vaginal cytology were compared before and after therapy. Estradiol levels remained suppressed after treatment to <8 pg/mL. Mean total symptom scores improved from 2.0 to 0.7 after treatment (p < .001) and remained improved 1 month thereafter (p = .003). Dyspareunia (p = .0014) and vaginal dryness (p <.001) improved. The median vaginal pH decreased from 5.5 to 5.0 (p = .028). The median maturation index rose from 20% to 40% (p < .001). Although improvement in total symptom score was similar for both doses (-1.3 for 300 μg, -0.8 for 150 μg; p = .37), only the 300-μg dose was associated with improved pH and maturation values. A 4-week course of vaginal testosterone was associated with improved signs and symptoms of vaginal atrophy related to AI therapy without increasing estradiol or testosterone levels. Longer-term trials are warranted.

Cancer biomarker HER-2/neu in breast cancer in Indian women

In Indian women with breast cancer, the HER-2/neu gene is amplified in 30% of cases. Elevated serum HER-2/neu levels have been shown to be associated with a poor clinical prognosis and decreased survival in early stage breast cancer patients, and testing for this may help to manage the disease. The present study was therefore to estimate serum HER-2/neu levels in breast cancer patients and associate these with other prognostic factors. Serum HER-2/neu levels were studied in 207 patients with breast cancer, 15 with benign breast diseases, (BBD) and 175 age-matched healthy controls. Patients' age, menopausal status, node, and estrogen receptor (ER) and progesterone receptor (PgR) status were compared with serum HER-2/neu levels. Serum HER-2/neu overexpression was associated with age, disease stage and positive nodal status but not with menopausal status. Serum HER-2/neu levels were negatively correlated with hormone receptor positivity. HER-2/neu serum tests should be done more frequently in Indian women with breast cancer, irrespective of their ER and PgR hormone receptor status. ELISA is a reliable and economical tool to assess the HER-2/neu status in tumors, when breast tissue samples are not available.

The correlation of anxiety and depression levels with response to neoadjuvant chemotherapy in patients with breast cancer

BackgroundThe aim was to evaluate and correlate anxiety and depression levels with response to neoadjuvant chemotherapy in patients with breast cancer. The study also assessed the effects of family support on distress levels.DesignIt was a prospective study in a cohort of 84 patients with locally advanced breast cancer. These assessments were done using the Hospital Anxiety and Depression Scale (HADS).SettingA prospective study in a developing world setting.ParticipantsEighty-four patients with locally advanced breast cancer receiving neoadjuvant chemotherapy were included after taking an informed consent and ethical committee clearance.Main outcome measuresA significant correlation was observed between response to neoadjuvant chemotherapy and depression levels in breast cancer patients. Joint family and literacy levels also had an impact on the levels of depression observed.ResultsA total of 84 patients receiving neoadjuvant chemotherapy for breast cancer were evaluated using HADS. The effect of family support, literacy levels and employment on the psychological status of these patients were also assessed.ConclusionsThe response to neoadjuvant chemotherapy had a direct correlation with the levels of depression, the distress levels being lower in responders. This was found to be the most important variable determining the psychological status of the patients. It was also observed that Indian patients in comparison to their Western counterparts react differently to cancer-related stress.

Clinical significance of preoperative serum interleukin-6 and C-reactive protein level in breast cancer patients

BackgroundBreast cancer is a disease that continues to plague females during their entire lifetime. IL-6 and CRP are found to be elevated in various inflammatory and malignant diseases and their levels are found to correlate with the extent of the disease. The primary objective of this study was to determine the preoperative serum levels of IL-6 and CRP in breast carcinoma, and to correlate them with the staging of the disease and the prognosis.Methods59 female patients admitted for breast cancer were identified for the study and were subjected to thorough evaluation. Serum levels of IL-6 were assessed via Enzyme-Linked Immuno-Sorbent Assay (ELISA), and CRP was measured via immunoturbidimetry. Histological findings included tumour size, lymph node (LN) metastasis, and tumour staging. Relevant investigations were made to find out the presence of distant metastasis. Statistical analysis of the data was then processed.ResultsIncreases in cancer invasion and staging are generally associated with increases in preoperative serum IL-6 levels. IL-6 and CRP levels correlated with LN metastasis (P < 0.001, P < 0.001) and TNM stage (P < 0.001, P < 0.001). Tumour invasion and the presence of distant metastasis is associated with higher IL-6 levels (P = 0.001, P = 0.009). When we established the cutoff value for IL-6 level (20.55 pg/dl) by ROC curve, we noted a significant difference in overall survival (OS; P = 0.008). However, CRP evidenced no significance with regard to patient's OS levels. Serum IL-6 levels were correlated positively with CRP levels (r2 = 0.579, P < 0.01)ConclusionSerum levels of IL-6 correlates well with the extent of tumor invasion, LN metastasis, distant metastasis and TNM staging thus enveloping all aspects of breast cancer.

Plasma Leptin, hTERT Gene Expression, and Anthropometric Measures in Obese and Non-Obese Women with Breast Cancer

Introduction:Expression of human telomerase reverse transcriptase (hTERT) occurs in most cancers but its relation with obesity is unclear. This study explores the association between leptin levels and anthropometric indices with hTERT mRNA levels in breast cancer patients of different obesity grades.Materials and methods:In this case-control study, 65 breast cancer patients participated. Expression of tissues hTERT mRNA was carried out by real-time reverse transcription polymerase chain reaction. Leptin concentrations were measured by enzyme-linked immunoassay.Results:Twelve patients (18.46%) were hTERT negative and 53(81.54%) were positive. hTERT mRNA levels were associated with BMI but not with waist circumference (WC) (r = 0.219, P = 0.22) and waist to hip ratio (WHR) (r = 0.212, P = 0.237). Leptin level and hTERT mRNA levels (r = 0.484, P = 0.008) were correlated as well as BMI and hTERT expression.Conclusions:This study has shown a correlation between leptin levels and hTERT expression. These findings may clarify the role of leptin in breast carcinogenesis, and hence obesity could be responsible for increased incidences in breast cancer as well as its progression via enhanced production of leptin.

Abstract P4-08-11: Surface Plasmon Resonance (SPR) Analysis of COX-2 Expression for Early Detection and Progression of Breast Cancer and Evaluation of a Novel Class of Peptides as Its Inhibitor

Abstract Background: Cyclooxygenase-2 (COX-2) over expression has been observed in different cancers. Till date, COX-2 expression in breast cancer has been studied using RT-PCR and immunohistochemistry. The aim of this study was to use surface plasmon resonance (SPR) technology for determining the expression levels of COX-2 in breast cancer and design peptide inhibitors to evaluate their enzyme inhibition in vitro. Patients and methods: This case-controlled study was performed on 84 biopsy proven breast cancer patients having invasive ductal carcinoma and 40 age, sex and ethnicity matched healthy subjects. Blood and tissue samples were collected and serum and tissue lysate was prepared. Serum and tissue levels of COX-2 were evaluated using SPR where samples were allowed to flow over anti-COX-2 antibody immobilized sensor chip to obtain the respective RUs. Similarly, standard curve of COX-2 was prepared from cloned, expressed and purified protein to deduce the concentrations in different samples. To evaluate enzyme inhibition, fifteen peptides were synthesized using the solid and solution-phase peptide synthesis based on the active site structure of COX-2 and enzyme activity was evaluated spectrophotometrically. Results: A significant increase in COX-2 levels in breast cancer patients 11.23-30.77μg/ml (Mean±SD=14.55±5.74) as compared to normal controls 2.13-5.16µg/ml (Mean±SD=3.71±0.86) (P&amp;gt;0.0001) was observed. Serum COX-2 levels were significantly higher (P&amp;lt;0.0061) in patients with lymph node involvement. More than 65% patients showed significantly (P&amp;lt;0.0025) reduced COX-2 levels after chemotherapy. This was confirmed by western blot to check tissue level expression and spectrophotometrically to determine the activity of COX-2 at different stages. In addition, the peptides showed significant in vitro enzyme inhibition, and had a KD ranging from 1 X 10-8 to 1X10-10. Conclusion: SPR is a useful proteomic technique for early detection and monitoring progession of breast cancer and peptides are a novel class of COX-2 inhibitors that can be further developed for anti-tumor therapy. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-08-11.

Reduced expression of ubiquitin ligase FBXW7 mRNA is associated with poor prognosis in breast cancer patients

FBXW7 is a cell cycle regulatory gene that ubiquitinates positive cell cycle regulators such as c-Myc and cyclin E, allowing for cell cycle exit. Defects in the FBXW7 gene that lead to cell cycle re-entry and expedite the G1-S transition is thought to be one of the causes of cancer development. However, its clinical importance for breast cancer patients remains undetermined. This prompted us to investigate its expression level in breast cancer patients to establish its clinical significance. The expression level of FBXW7 mRNA was assessed in 186 cases of primary invasive breast cancer. Correlations between FBXW7 mRNA expression and clinicopathological factors, prognoses and immunohistochemical expression levels of Ki-67, FBXW7, c-Myc and cyclin E were analyzed. In vitro investigation of FBXW7 gene silencing in a breast cancer cell line was conducted. FBXW7 mRNA was expressed at significantly lower levels in patients with high histological grade and hormone receptor-negative tumors. Patients with lower FBXW7 mRNA expression had a poorer prognosis for breast cancer-specific survival than those with higher expression. A high Ki-67 labeling index and positive cyclin E protein expression were significantly correlated with lower FBXW7 mRNA expression. In vitro, silencing FBXW7 enhanced expression of c-Myc and cyclin E proteins and upregulated both cell proliferation and G1-S transition. In breast cancer, reduced FBXW7 mRNA expression may have independent prognostic potential through the enhanced function of cell cycle regulatory proteins.

Hemoglobin and Aerobic Fitness Changes with Supervised Exercise Training in Breast Cancer Patients Receiving Chemotherapy

Aerobic exercise training (AET) is known to increase RBC production; however, this has not been evaluated in breast cancer patients undergoing adjuvant chemotherapy. The purpose of this study was to examine the changes in hemoglobin (Hb) levels in the Supervised Trial of Aerobic versus Resistance Training (START) and to determine its association with changes in VO(2peak). Two hundred and forty-two breast cancer patients initiating chemotherapy were randomized to usual care (n = 82), resistance exercise (RET, n = 82), or AET (n = 78) groups for the duration of their chemotherapy (median, 17 weeks). Supervised exercise was thrice weekly based on standard AET and RET prescriptions. Aerobic fitness (VO(2peak)) and Hb concentration were measured at baseline and end of chemotherapy. Regardless of the exercise group, Hb declined over the course of chemotherapy (13.4 ± 10.0 to 11.8 ± 11.5 g/dL, P < 0.01). Both AET and RET groups had significant, moderate correlations between the change in VO(2peak) and Hb (AET: r = 0.49, P < 0.001; RET: r = 0.39, P = 0.001). The results indicate that regular exercise does not protect against the decline in Hb associated with chemotherapy in breast cancer patients, but resulted in a stronger association between Hb and VO(2peak). Even with the chemotherapy-induced decline in Hb, breast cancer patients can maintain their aerobic capacity by participating in regular aerobic exercise. Further studies are required to determine safe intensity levels that may stimulate the maintenance of Hb levels in breast cancer patients.

Troglitazone suppresses telomerase activity independently of PPARγ in estrogen-receptor negative breast cancer cells

BackgroundBreast cancer is one the highest causes of female cancer death worldwide. Many standard chemotherapeutic agents currently used to treat breast cancer are relatively non-specific and act on all rapidly dividing cells. In recent years, more specific targeted therapies have been introduced. It is known that telomerase is active in over 90% of breast cancer tumors but inactive in adjacent normal tissues. The prevalence of active telomerase in breast cancer patients makes telomerase an attractive therapeutic target. Recent evidence suggests that telomerase activity can be suppressed by peroxisome proliferator activated receptor gamma (PPARγ). However, its effect on telomerase regulation in breast cancer has not been investigated.MethodsIn this study, we investigated the effect of the PPARγ ligand, troglitazone, on telomerase activity in the MDA-MB-231 breast cancer cell line. Real time RT-PCR and telomerase activity assays were used to evaluate the effect of troglitazone. MDA-MB-231 cells had PPARγ expression silenced using shRNA interference.ResultsWe demonstrated that troglitazone reduced the mRNA expression of hTERT and telomerase activity in the MDA-MB-231 breast cancer cell line. Troglitazone reduced telomerase activity even in the absence of PPARγ. In agreement with this result, we found no correlation between PPARγ and hTERT mRNA transcript levels in breast cancer patients. Statistical significance was determined using Pearson correlation and the paired Student's t test.ConclusionsTo our knowledge, this is the first time that the effect of troglitazone on telomerase activity in breast cancer cells has been investigated. Our data suggest that troglitazone may be used as an anti-telomerase agent; however, the mechanism underlying this inhibitory effect remains to be determined.

Plasma VEGF levels in breast cancer patients with and without metastases

Vascular endothelial growth factor (VEGF) is a key mediator of angiogenesis since it stimulates the formation of new blood vessels. Basic fibroblast growth factor (bFGF) is related to the promotion of endothelial cells into tube-like structures, and it is therefore expected to promote angiogenesis with a greater potency than VEGF. VEGF and bFGF are considered to be biomarkers that predict treatment effectiveness. Elevated plasma VEGF and bFGF levels have been reported in a variety of different malignant tumors, and patients with metastatic disease have also been reported to present with higher serum VEGF and bFGF levels. Other studies have documented controversial results with respect to the prognostic and predictive value of the aforementioned biomarkers. This study aimed to determine the plasma VEGF and bFGF levels in breast cancer patients without metastatic disease compared with breast cancer patients with advanced metastatic disease. The study included 93 patients with breast cancer, 46 without recurrent disease (group A) and 47 with metastatic disease (group B), as well as 21 healthy individuals. The median age was 58 years (range 34-78) for group A and 59 years (range 37-75) for group B. All 93 patients underwent chemotherapy, adjuvant for group A, and adjuvant plus chemotherapy for group B patients with advanced disease. Plasma VEGF and bFGF levels were determined using a quantitative sandwich immunoassay, and samples were tested in triplicate (ELISA). The plasma levels of VEGF and bFGF varied greatly, i.e., from extremely low to extremely high in the two groups, as well as in the healthy individuals. No statistically significant difference was found between the two groups or between the patients and healthy individuals. Data of the present study therefore showed that VEGF and bFGF levels are not valuable biomarkers for predicting treatment outcome.

Effect of BRCA1 gene and estrogen-receptor α on regulation of serum estradiol levels in women with breast cancer.

1536 Background: A BRCA1 gene mutation is well-known risk factor for breast cancer. Recently, BRCA1 gene was found to negatively regulate aromatase expression in a human granulosa cell line and also modulate estrogen-receptor α (ERα). We evaluated the estradiol (E2) levels in breast cancer patients in association with BRCA1 gene mutation and ERα status. Methods: We performed a secondary analysis of the Controlled Ovarian Stimulation Treatment with Letrozole Supplementation Study (COST-LESS, JCO 2009). Sixty-four women with breast cancer who underwent BRCA testing with known ERα status, and who were undergoing oocyte/embryo cryopreservation for fertility preservation were included. Results: The mean menstrual cycle day-2 E2 level was significantly higher in BRCA1 mutation/ERα-positive women compared to ERα and/or BRCA1 mutation negative women. Compared to BRCA1 mutation-negative women, the relative rise in E2 from baseline to the peak levels in response to ovarian stimulation was lower in BRCA1 mutation/ERα-positive women (Table). Conclusions: We speculate that under the upregulated aromatase expression in BRCA1 mutation-positive women, ERα may act as a scavenger to E2, which in turn increases E2 levels through a negative feedback. The lower relative rise of E2 in BRCA1 mutation/ERα-positive women in response to ovarian stimulation with letrozole might reflect the fact that aromatase activity is increased in this group and hence an aromatase inhibitor has a stronger effect in suppressing aromatization of androgens to estrogens. From the latter, one can speculate that aromatase inhibitors may have a stronger benefit in breast cancer treatment in BRCA1 mutation/ERα-positive women. We propose that BRCA1 gene and ERα may coregulate E2 levels in breast cancer. BRCA1 mutation (-) BRCA1 mutation (+) p value ERα (-)a(n=4) ERα (+)b(n=50) ERα (-)c(n=6) ERα (+)d(n=4) Age (years) 32.0 ± 5.7 35.5 ± 4.6 32.2 ± 4.6 32.5 ± 3.5 NS Day2 E2 (pg/mL) 31.5 ± 8.7 34.8 ± 11.9 33.4 ± 11.8 61.4 ± 21.5 d vs. a, b, c:≤0.001 Relative rise of E2 (%) (95% C.I.) 894.0(285.2∼1,502.9) 1,490.5(1,024.5∼1956.5) 1,062.8(494.8∼1630.8) 746.2(-1092.0∼2584.4) d vs. b, (a + b):0.028 No significant financial relationships to disclose.

Intratumoral Estrogen Disposition in Breast Cancer

The concentration of estradiol (E(2)) in breast tumors is significantly higher than that in plasma, particularly in postmenopausal women. The contribution of local E(2) synthesis versus uptake of E(2) from the circulation is controversial. Our aim was to identify possible determinants of intratumoral E(2) levels in breast cancer patients. The expression of genes involved in estrogen synthesis, metabolism, and signaling was measured in 34 matched samples of breast tumor and normal breast tissue, and their correlation with estrogen concentrations assessed. ESR1 (9.1-fold; P < 0.001) and HSD17B7 (3.5-fold; P < 0.001) were upregulated in ER(+) tumors compared with normal tissues, whereas STS (0.34-fold; P < 0.001) and HSD17B5 (0.23-fold; P < 0.001) were downregulated. Intratumoral E(2) levels showed a strong positive correlation with ESR1 expression in all patients (Spearman r = 0.55, P < 0.001) and among the subgroups of postmenopausal (r = 0.76, P < 0.001; n = 23) and postmenopausal ER(+) patients (r = 0.59, P = 0.013; n = 17). HSD17B7 expression showed a significant positive correlation (r = 0.59, P < 0.001) whereas HSD17B2 (r = -0.46, P = 0.0057) and HSD17B12 (r = -0.45, P = 0.0076) showed significant negative correlations with intratumoral E(2) in all patients. Intratumoral E(2) revealed no correlation to CYP19, STS, and HSD17B1 expression. Multivariate models comprising ESR1 and plasma E(2) predicted between 50% and 70% of intratumoral E(2) variability. Uptake due to binding to the ER, rather than intratumoral estrogen synthesis by aromatase or sulfatase, is the single most important correlate and a probable determinant of intratumoral E(2). An increased expression of HSD17B7 may explain the increased ratio of E(2) to estrone (E(1)) in breast tumors compared with normal tissue.

142 Prognostic effect of serum 25-hydroxyvitamin D levels in breast cancer patients

The aim of the study was to investigate the role of lymphangiogenesis in human cervical cancer progression.The expression of VEGF-C, VEGF-D, VEGFR-3, podoplanin (D2-40), LYVE-1 and Prox-1 was studied by immunohistochemistry in 72 cases of invasive squamous cell carcinoma of the uterine cervix. For lymphatic endothelial markers lymphatic vessel density (LVD) was assessed. Correlations with lymphatic vessel invasion, nodal metastases, tumour grade, FIGO stage, and inflammation were also evaluated.VEGF-D expression significantly correlated with lymph node metastasis, lymphatic emboli and FIGO stage as well as with peritumoural LVD. A marginally significant correlation was also found between the expression of VEGF-C and prognostic parameters. Lymphatic tumour emboli were successfully identified using D2-40 immunohistochemistry and peritumoural D2-40 LVD significantly correlated with lymphatic vessel invasion. However, LVD as assessed by multiple lymphatic markers was not associated with lymphatic metastasis. There was a significant correlation of Prox-1 and LYVE-1 LVD with the inflammatory stromal reaction.Although LVD as assessed by multiple lymphatic markers was not correlated with prognostic parameters, tumour expression of lymphangiogenic growth factors seems to be critically implicated in lymphatic metastasis and cervical carcinoma progression.

Circulating microRNAs as Novel Minimally Invasive Biomarkers for Breast Cancer

The development of clinically validated biomarkers for cancer has remained an insurmountable task despite other advances in the field of cancer molecular biology. Mi(cro)RNAs have many characteristics of an ideal biomarker most notably their inherent stability and resilience. Recent blood-based miRNA profiling studies, reporting their presence in serum and plasma, have generated the concept that circulating miRNAs hold much potential as novel noninvasive biomarkers for cancer and other disease processes. The objective of this study was to investigate the potential of circulating microRNAs as novel breast cancer biomarkers. Using a novel approach to extract miRNAs from the circulation followed by real-time quantitative polymerase chain reaction analysis, levels of a panel of 7 candidate miRNAs were quantified in tissue and blood specimens of 148 patients with breast cancer and 44 age-matched and disease free control individuals. We report that cancer-specific miRNAs were detected and significantly altered in the circulation of breast cancer patients, and that increased systemic miR-195 levels in breast cancer patients were reflected in breast tumors. Furthermore, we identified that circulating levels of miR-195 and let-7a decreased in cancer patients postoperatively, to levels comparable with control subjects, following curative tumor resection. Finally, we found that specific circulating miRNAs correlated with certain clinicopathological variables, namely nodal status and estrogen receptor status. These findings suggest that systemic miRNAs have potential use as novel breast cancer biomarkers and may prove useful in clinical management during the perioperative period.

Systemic MiRNA Levels as Novel Breast Cancer Biomarkers.

Abstract Background: The development of clinically validated biomarkers for breast cancer has remained an insurmountable task despite other advances in the field of molecular biology. Mi(cro)RNAs have many characteristics of an ideal biomarker most notably their inherent stability, resilience, and ease of detection. Recent blood based miRNA profiling studies, reporting their presence in serum and plasma, have generated the concept that circulating miRNAs hold much potential as novel non-invasive biomarkers for cancer and other disease processes. The objective of this study was to investigate the potential of circulating microRNAs as novel breast cancer biomarkers.Materials and Methods: Using a real-time quantitative PCR approach, expression levels of a panel of 7 oncogenic miRNAs were quantified in tissue and blood specimens of 148 patients with breast cancer and 24 age-matched disease free control individuals. Advanced QBase Plus software and SPSS were used for biostatistical analysis of the data, and correlation with clinicopathological variables.Results: Cancer specific miRNAs were detected and significantly altered in the circulation of breast cancer patients preoperatively, most notably miR-195 (12 fold increase) and let-7a (5-fold increase), (p &amp;lt; 0.001 and p&amp;lt;0.001 respectively). Increased systemic miR-195 levels in breast cancer patients were also reflected in breast tumors. Systemic let-7a levels varied inversely with disease stage, being highest in carcinoma in-situ patients and getting progressively lower through to stage IV invasive disease. Furthermore we identified that circulating levels of miR-195 and let-7a decreased in cancer patients post-operatively following curative tumor resection (p&amp;lt;0.001 and p&amp;lt;0.001 respectively). Finally we found that specific circulating miRNAs correlated with certain clinicopathological variables, namely nodal status and estrogen receptor statusDiscussion/Conclusion: Our results demonstrates the novel finding that miRNAs are detectable in the circulation of breast cancer patients, that expression profiles differ between patients and controls, and that the circulating miRNA expression profile correlates with various biopathologic parameters of breast cancer. Also, systemic miRNA levels revert to normal levels following tumour resection. In this, lies the expectation that systemic miRNAs will be clinically useful as a novel minimally invasive tool to aid in the early diagnosis and perioperative management of breast cancer. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 32.

Human Circulating Endorepellin LG3 Fragment and Breast Density: A Potential Combination with Screening Mammography in Women with Dense Breast.

Abstract (Background) In vitro studies have reported that the endorepellin LG3 fragment (ERLG3F), which is matrix-derived endogenous anti-angiogenic factor, can be a circulating biomarker candidate for breast cancer. This study examined the plasma ERLG3F levels in breast cancer patients and normal healthy controls, and evaluated its potential roles as a screening biomarker for breast cancer (Methods) ERLG3F levels were determined by competitive ELISA in the plasmas from prospectively constructed independent cohorts (train and test set) from July 2006 to September 2007 for the Biomarker Discovery Project (funded by 21C Frontier Functional Proteomics Program of South Korea). The Breast Cancer Cohort (BC) (n=366) has plasmas drawn preoperatively; the Healthy Control Cohort (HC) (n=305), drawn when volunteers visited our Healthcare Center for medical check-up. Circulating ERLG3F, mammography, and the combining marker (CM) of both were evaluated for their performance of identifying breast cancer in the train set and verified again in the test set. (Results) Decreased ERLG3F levels were observed in the individual plasmas from BC compared to the HC. The decrease was significantly prominent in patients without axillary lymph node metastasis (negative vs. positive), young age (&amp;lt; 50 vs. ≥50 yr), and dense breast (mammographic density Gr 3 or 4 vs. 1 or 2). We used a cutoff level, which correspond to 2SD below the mean ERLG3F in total healthy controls. ERLG3F significantly improved the performance of mammography in distinguishing breast cancer cases from healthy controls, although it is less sensitive than mammography as a single marker. (Conclusion) We conclude that ERLG3F can be a useful diagnostic biomarker for breast cancer and its role can be even better when used for young women with dense breast for whom mammography is less helpful. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3026.

Prognostic Effect of Sesrum 25 Hydroxyvitamin D Levels in Breast Cancer Patients.

Abstract BackgroundThere is increasing evidence that vitamin D has been linked to breast cancer risk, but prognosis effect are unknown. We investigated the possible association between vitamin D and breast cancer prognosis by comparing serum vitamin D levelMethodsFrom June to December 2006, serum 25 OHD were measured in 310 Korean women with breast cancer at the Asan Medical Center. Clinical, Pathologic, and dietary data were accessed to examine prognostic effects of serum 25 OHDResultsMean age was 48.7 years, mean serum 25OHD was 31.4±16.1ng/ml. 25OHD levels were deficient(&amp;lt;20ng/ml) in 24.2%, insufficient (20-29ng/ml) in 30.6%, and sufficient(30-150ng/ml) in 24.0%. Mean follow up was 30 months: 31 had recurrences. Women with deficient 25 OHD levels had an increased risk of recurrence(HR=2.93;95% CI=1.27 to 6.77) compared with those with sufficient levels. 25OHD levels were inversely associated with prognosis of hormone receptor positive tumors, but not with hormone receptor negative tumors(HR=5.73 95CI=1.82 to 18.06 for hormone receptor positive tumor, HR=1.142, 95%CI =0.33 to 3.92 for hormone receptor negative tumor). The association remained after individual adjustment for age, tumor size, nodal status, estrogen receptor status (HR=4.13 95%CI=1.77 to 9.61) .ConclusionVitamin D deficiency may be associated with poor outcomes in hormone receptor positive breast cancer patients. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1052.

TNF receptor p55 and IL-872 and IL-877 isoforms: blood and urine levels in breast cancer patients

In the preliminary study reported here, 37 patients with breast cancer and 10 healthy volunteers were analyzed for soluble TNF-R p55 and two variants of IL-8 consisting of 72 and 77 amino acid residues (IL-872 and IL-877, respectively) in their blood and urine with novel ELISA test systems. The clinical/prognostic values of determining these inflammatory cytokines at different stages of the cancer process appeared to depend on the treatment course being evaluated. In contrast to expectations, it was noted that there was a stabile tendency for decreased TNF-R p55 and IL-872 levels in the plasma and urine of breast cancer patients as compared with levels observed with healthy controls. Moreover, patients that underwent polychemotherapy treatments were notable for significant decreases in IL-872 and TNF-R p55 levels in their blood plasma; these findings contrasted with significant increases in these parameters in these patients’ urine. Interestingly, the IL-877 isoform that now appeared both in the urine and plasma of patients was not detectable before initiation of the polychemotherapy. In spite of all these findings, individual fluctuations among these parameters still do not allow us to establish, at this time, any strong correlations between these values with any particular breast cancer stage or a type of treatment. Nonetheless, while the results here are preliminary, they demonstrate that testing for TNF-R, along with IL-8 isoforms, in the blood plasma and urine could potentially present a valid means for monitoring of the overall immune and disease progress/remission status in breast cancer patients. Ongoing studies with larger patient sample sizes, as well as collecting and analyzing samples at multiple timepoints—to minimize the potential influence of any inherent variability in cytokine levels in humans—will hopefully allow us to specify what these preliminary results reported here suggest, i.e., the potential utility of this experimental approach for determining disease progression or efficacy of treatment in cancer patients.

The effects of tamoxifen on homocysteine levels in breast cancer patients

Abstract Tamoxifen is widely used in the treatment of breast cancer and associated with an increased risk of thromboembolism (TE). An elevated homocysteine is one of the risk factors for TE. The aim of the study was to assess the effect of tamoxifen on serum homocysteine levels in breast cancer patients. We performed a case-control study in 20 female subjects to evaluate the relationship between homocysteine levels, and 5,10-methylenetetrahyrofolate reductase (MTHFR) C677T and dihydrofolate reductase (DHFR) 19-bp intron-1 deletion polymorphisms in breast cancer patients and in control subjects. It was observed that homocysteine levels were decreased during tamoxifen therapy, but this finding was not statistically significant. There was also no statistically significant difference in homocysteine levels between the two groups (p&gt; 0.05). MTHFR C677T and DHFR 19-bp deletion polymorphisms were not associated with serum homocysteine value in either group.