Profile Of Breast Cancer Patients Research Articles

Microarray phosphatome profiling of breast cancer patients unveils a complex phosphatase regulatory role of the MAPK and PI3K pathways in estrogen receptor-negative breast cancers.

Phosphatases are proteins with the ability to dephosphorylate different substrates and are involved in critical cellular processes such as proliferation, tumor suppression, motility and survival. Little is known about their role in the different breast cancer (BC) phenotypes. We carried out micro-array phosphatome profiling in 41 estrogen receptor-negative (ER−) BC patients, as determined by immunohistochemistry (IHC), containing both ERBB2+ and ERBB2− in order to characterize the differences between these two groups. We characterized and confirmed the distinct phosphatome of the two main ER− BC subgroups (in two independent microarrays series) and that of ER+ BC (in three large independent series). Our findings point to the importance of the MAPK and PI3K pathways in ER− BCs as some of the most differentially expressed phosphatases (like DUSP4 and DUSP6) sharing ERK as substrate, or regulating the PI3K pathway (INPP4B, PTEN). It was possible to identify a selective group of phosphatases upregulated only in the ER− ERBB2+ subgroup and not in ER+ (like DUSP6, DUSP10 and PPAPDC1A among others), suggesting a role of these phosphatases in specific BC subtypes, unlike other differentially expressed phosphatases (DUSP4 and ENPP1) that seemed to have a role in multiple BC subtypes. Significant correlation was found at the protein level by IHC between the expression of DUSP6 and phospho-ERK (p=0.04) but not of phospho-ERK with DUSP4. To show the potential prognostic relevance of phosphatases as a functional group of genes, we derived and validated in two large independent BC microarray series a multiphosphatase signature enriched in differentially expressed phosphatases, to predict distant metastasis-free survival (DMFS). ER− ERBB2+, ER− ERBB2− and ER+ BC patients have a distinct pattern of phosphatase RNA expression with a potential prognostic relevance. Further studies of the most relevant phosphatases found in this study are warranted.

The oxidative profile in breast cancer patients according to their HER2 status

The oxidative profile in breast cancer patients according to their HER2 status

A retrospective study of clinico-pathological spectrum of carcinoma breast in a West Delhi, India.

Background:Data on the demographic profile of breast cancer patients from Delhi is scarce and whatever is available is from higher referral center. Our hospital caters to patients from an urban population of the lower socioeconomic strata and is a representation of cases at a tertiary care hospital in west Delhi. In Delhi, breast cancer (26.8%) is commonest cancer among the female followed by cervix (12.5%), gallbladder (7.2%), ovary (7.1%), and uterus (3.3%).Aims and Objectives:A retrospective audit of breast cancer patients presenting at a tertiary referral center from 2004 to 2011.Materials and Methods:A total of 328 cases diagnosed as carcinoma breast on histopathology from year 2004 to 2011 were retrieved and studied retrospectively with regards to demographic profile and their histological features with estrogen receptor (ER), progesterone receptor (PR), and Her2neu status.Results:The median age of presentation was 49 years of age. Infiltrating ductal carcinoma (IDC, not otherwise specified (NOS)) was the commonest histopathological variant (81.40%) followed by medullary carcinoma (10.36%) and mucinous carcinoma (2.74%). Triple negative were found to be the commonest group comprising 39.4% of all the cases followed by ER and PR both positive. Pathological tumor, node, and metastasis (TNM) staging showed most common group was T2N0M0 (19.5%) followed by T2N1M0 (17.1%) and T2N2M0 (14%).Conclusion:The incidence of breast cancer in the India and include a higher incidence of ER, PR, and Her2neu negative disease in west Delhi.

Adjuvant Tamoxifen Influences the Lipid Profile in Breast Cancer Patients

Background: Currently there is a debate regarding whether tamoxifen used in breast cancer has an impact on lipid profiles. The aim of this study was to determine whether tamoxifen has an impact on the serum lipid profile in Taiwanese women. Patients and Methods: Data of 109 patients were collected from the routine clinical follow-up for women with hormone receptor-positive breast cancer who were treated between July 2005 and March 2008. These patients were divided into 2 subgroups, based on their tumor grade and lymph node status. Subgroup 1 patients had tumor grade I/II and a negative lymph node status. Those patients with tumor grade III or a positive lymph node status were defined as subgroup 2. Results: In the 109 patients, the mean serum total cholesterol (TC) levels after tamoxifen treatment, as well as the serum low-density lipoprotein cholesterol (LDL-C) levels, were lower than the baseline levels, with statistically significant differences. Treatment with tamoxifen lowered the serum TC and LDL-C levels in both subgroups. Conclusions: The results indicate that tamoxifen has an impact on the serum lipid profile of breast cancer patients in Taiwan. Physicians should follow up the lipid profile in these patients.

Psychopathological Profile of Women with Breast Cancer Based on the Symptom Checklist-90-R

With effective early treatments, many breast cancer patients suffer from psychological distress due to adverse effects and lifelong physical disfigurement. Our study aimed to evaluate the psychopathological profile of breast cancer patients in comparison with healthy women and explored demographic correlates. We consecutively enrolled breast cancer patients who came to the hospital for follow-up or rehabilitation care after primary treatment, and healthy female relatives or friends of inpatients in the Cancer Institute of Chinese Academy of Medical Sciences between August 30, 2010 and January 1, 2012. Psychopathological profile was assessed based on the Symptom Checklist-90-R (SCL-90-R) for patients and controls. We compared demographics such as age, ethnicity, education, marriage, and occupation, and incorporated these data plus cancer status for the association with the general SCL-90-R index and scores for 9 major symptom dimensions in multiple regression analysis. We surveyed a total of 291 female breast cancer patients and 531 healthy women. The average age was 55.1 ± 6.40 years for breast cancer patients and 43.1 ± 12.8 for healthy controls (P<0.01). The mean survival was 5.20 years for cancer patients (range, 0.60-9.90 years). There were statistically significant differences in education, marriage, and occupation between the two groups (P<0.01). General index (1.45 ± 0.45 versus 1.32 ± 0.37) and 8 dimension scores (excluding anxiety) on SCL-90-R were significantly higher in patients (P<0.05). Multiple regression analysis showed that the breast cancer status was positively correlated with general SCL-90-R index and 6 dimension scores (excluding the anxiety, phobic anxiety and paranoid ideation dimensions) (P<0.05). Regression coefficients ranged from 0.10 (depression) to 0.19 (somatization). Higher interpersonal sensitivity was noticed in single women compared to married women. Chinese patients with breast cancer demonstrate greater psychopathology compared to healthy controls. The breast cancer status is an independent contributing factor to the general psychopathological profile. Breast cancer patients should be given particular counseling and care to alleviate their psychological distress.

Abstract 160: Modulation of the serum metabolomic profiles of breast cancer patients after receiving limonene intervention.

Abstract Background. Limonene is a bioactive food component found in citrus peel oil that has demonstrated chemopreventive and chemotherapeutic activities in preclinical studies. To better characterize its mechanism of action in the clinical setting, we measured the serum metabolomic profiles of breast cancer patients before and after receiving a short-term limonene intervention. Methods. Forty women with stage 0 - II breast cancer received 2 g QD limonene daily for 2 - 6 weeks (21.5 ± 8.8 days) before surgical resection of their tumor. Pre/post intervention blood draws were taken to assess serum metabolomic profiles. Metabolomic analysis was performed on the gas chromatography mass spectrometry and liquid chromatography mass spectrometry platforms established at Metabolon, Inc. Results. Of the 397 identified biochemicals, 71 changed significantly (p&amp;lt;0.05) from baseline to post limonene intervention. Pathway analysis revealed several key metabolic changes. Significant increases were noted in eight bile acid conjugates following limonene intervention, including a 3-fold elevation in taurocholate, taurodeoxycholate, and glycoursodeoxycholate. There were also significant decreases in a number of steroid hormones including dehydroisoandrosterone sulfate (DHEA-S), 4-androsten-3beta, 17beta-diol disulfate, epiandrosterone sulfate, androsterone sulfate, and pregnen-diol disulfate. In addition, markers of collagen remodeling or degradation were elevated following limonene intervention. Increased circulating vitamin C, improved insulin sensitivity and glycemic control, and reduced inflammatory potential were also noted following limonene treatment. An increase in plasma levels of ten different glycerophosphocholines and four carnitines were all significantly correlated to a decrease in cyclinD1 (all p's&amp;lt;0.01 and Rˆ2&amp;gt;0.4) in an exploratory analysis. Conclusions. This global metabolomic profiling study revealed several novel mechanistic insights into the potential clinical activities of limonene. Efforts are ongoing to correlate these metabolic changes to carcinogenesis, clinical characteristics, and risk markers measured in breast tissue and serum. Citation Format: Jessica A. Miller, Kirk Pappan, Chengcheng Hu, Elizabeth J. Want, Hector Keun, Julie E. Lang, H-H Sherry Chow. Modulation of the serum metabolomic profiles of breast cancer patients after receiving limonene intervention. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 160. doi:10.1158/1538-7445.AM2013-160

Mass Spectrometry-Based Quantitative Metabolomics Revealed a Distinct Lipid Profile in Breast Cancer Patients

Breast cancer accounts for the largest number of newly diagnosed cases in female cancer patients. Although mammography is a powerful screening tool, about 20% of breast cancer cases cannot be detected by this method. New diagnostic biomarkers for breast cancer are necessary. Here, we used a mass spectrometry-based quantitative metabolomics method to analyze plasma samples from 55 breast cancer patients and 25 healthy controls. A number of 30 patients and 20 age-matched healthy controls were used as a training dataset to establish a diagnostic model and to identify potential biomarkers. The remaining samples were used as a validation dataset to evaluate the predictive accuracy for the established model. Distinct separation was obtained from an orthogonal partial least squares-discriminant analysis (OPLS-DA) model with good prediction accuracy. Based on this analysis, 39 differentiating metabolites were identified, including significantly lower levels of lysophosphatidylcholines and higher levels of sphingomyelins in the plasma samples obtained from breast cancer patients compared with healthy controls. Using logical regression, a diagnostic equation based on three metabolites (lysoPC a C16:0, PC ae C42:5 and PC aa C34:2) successfully differentiated breast cancer patients from healthy controls, with a sensitivity of 98.1% and a specificity of 96.0%.

Plasma Protein Profiling of Breast Cancer Patients of North Indian Population: A Potential Approach to Early Detection

Study background: Over the last two decades worldwide the mortality due to breast cancer (BC) raises catastrophically. Unfortunately, clinicians are still seeking for reliable resources for early speculations. Recently, the approach of investigative plasma based molecular markers builds a new hope for the early stage diseases. Methods: Blood samples of healthy and BC individuals from North Indian women (n=25) were collected. In order to increase the detecting sensitivity of protein of interest, the pooled plasma samples were subjected to Multiple affinity removal system (MARS) Hu-14 and PROTEOPREP 20 and further processed by 2D-PAGE/LCMS/ MS analysis. Finally, the levels of selected proteins were independently estimated by western blotting and immunohistochemistry. Results: The comparative 1D-SDS page and 2DE gel analysis showed the high proficiency of Hu-14 MARS for diminution of HAPs. The proteome profile of pooled plasma sample yielded total 24 differentially expressed spots in BC over control. Among them, the identified 3 up-regulated proteins, Serpin peptidase inhibitor clade A (privilege 92%; 95%CI 79.36-104.63), Apolipoprotein A IV (privilege 72%; 95%CI 52.4-91.6), Apolipoprotein AI (privilege 92%; 95%CI 79.36-104.63), and 1 down-regulated α-2-HS glycoprotein (privilege 76%; 95%CI 57.26-94.74) spots were of high significance (p<0.05). These proteins are involved in pathogenesis of cancer and play an important role in the regulation of metastasis. However their discerned molecular mechanisms evaluation related to BC is ongoing to scrutinize its clinical utility. Importantly, the results of immunochemical quantifications were found consistent with the changes in 2-DE check for all candidates apart from α-2-HS glycoprotein, where the immunohistochemistry analysis was not correlated well with 2DE and immunoblotting. Conclusion: This preliminary work presents a panel of differential plasma proteins in BC patients, validated by combining routine clinical immunochemical reactions for the first time in North India. Further, in order to establish a cause and effect relationship of these highly modulated proteins with BC needs large scale sample size investigation.

Serum Lipid Profile of Breast Cancer Patients in Kashmir

Malignancy of the breast is one of the commonest causes of death in women aged between 40-45 years. The aim of this study was to carry out a comparative study to investigate the effect of lipid profile, oestradiol (EST) and obesity on the risk of a woman developing breast cancer. In this study, 120 women including 60 breast cancer patients (25 to 80 years) were assessed for lipid profile, EST and Body Mass Index (BMI) and 60 controls with similar age range. There was a significant increase in Body Mass Index (BMI) (p = 0.011), Total Cholesterol (TC) (p

Body mass index and serum proteomic profile in breast cancer and healthy women: a prospective study.

Epidemiological studies suggest a possible association between BMI, diagnosis and clinical-pathological breast cancer characteristics but biological bases for this relationship still remain to be ascertained. Several biological mechanisms play a role in the genesis and progression of breast cancer. This study aimed to investigate relationships between BMI and breast cancer diagnosis/progression in a Southern Italian population and to try to interpret results according to the serum proteomic profile of healthy and breast cancer patients.BMI, presence or absence of breast cancer and its clinical-pathological characteristics were analyzed in a series of 300 breast cancer women and compared with those of 300 healthy women prospectively. To investigate whether obesity is associated with alterations in serum protein profile, SELDI-ToF approach was applied.Alcohol consumption (22.7% vs 11.3%; p<0.001) and postmenopausal status (65.7% vs 52%; p<0.001) but not BMI resulted significantly different in patients vs controls. Conversely, BMI was significantly associated with a larger-tumour size (BMI> = 30 respect to normal weight: OR = 2.49, 95% CI 1.25–4.99, p = 0.0098) and a higher probability of having positive axillary lymph node (OR = 3.67, CI 95% 2.16–6.23, p<0.0001). Multivariate analysis confirmed the association of breast cancer diagnosis with alcohol consumption (OR = 2.28;CI 1.36–3.83; p<0.0018). Serum protein profile revealed the presence of significant (p-value <0,01) differentially expressed peaks m/z 6934, m/z 5066 in high BMI breast cancer patients vs healthy subjects and m/z 6934, m/z 3346 in high vs low BMI breast cancer patients.The analysis of pathological features of cancer indicates that normal weight women have a significantly higher probability of having a smaller breast cancer at time of diagnosis and negative axillary lymph nodes while increased BMI is associated with an altered protein profile in breast cancer patients. Further studies to identify specific proteins found in the serum and their role in breast cancerogenesis and progression are in progress.

Putative circulating markers of the early and advanced stages of breast cancer identified by high-resolution label-free proteomics

This study evaluated the plasmatic proteomic profile of breast cancer patients in the early (ED) and advanced (AD) stages, employing high-throughput proteomics. We identified 92 differentially expressed proteins in ED and 73 proteins in AD patients. Gelsolin, lumican, clusterin, SALL4 and PMS2, as well hTERT, TNF-α and GRHL3 were chosen for further investigation. ED presented augmented expression of GRHL3 and reduced circulating TNF-α with high expression of GRHL3 in tumors. AD displayed high TNF-α and a significant expression of PMS2 in tumors. These findings suggest processes enrolling stem cell division in ED, with TNF-α signaling and DNA mismatch repair in the advanced stage.

Cardio-Oncology: Cardiac Risk Profile in Breast Cancer Patients With Stage A Heart Failure

Cardio-Oncology: Cardiac Risk Profile in Breast Cancer Patients With Stage A Heart Failure

Clinicopathologic Profile of Breast Cancer Patients in Pakistan: Ten Years Data of a Local Cancer Hospital

Breast cancer is the most frequent cancer of women worldwide, with considerable geographic and racial/ethnic variation. Data are generally derived from population based cancer registries in the developed countries but hospital data are the most reliable source in the developing countries. Ten years data from 1st Jan 2000 to 31st Dec 2009 of a cancer hospital in Pakistan were here analyzed by descriptive statistics to evaluate the clinicopathologic profile of local breast cancer patients. Among 28,740 cancer patients, 6,718 were registered as breast cancer. The female to male ratio was 100:2. Breast cancer accounted for 23% of all and 41% of female cancers. Some 46% were residents of Lahore, with a mean age of 47±12 years. Less than 1% were at Stage 0 and 10%, 32%, 35% and 23% were at Stage I, II, III and IV respectively. Histopathology was unknown in 4% while 91%, 2% and 1% had invasive ductal carcinoma (IDC), invasive lobular carcinoma (ILC) and mucinous carcinoma respectively. Rare carcinomas accounted for the rest. Tumor grade 1, 2 and 3 was 11%, 55% and 34% among the known. Profile of breast cancer patients in Pakistan follows a pattern similar to that of other developing countries with earlier peak age and advanced disease stage at presentation. The male breast cancer accounts for higher proportion in the local population. Local women have higher frequency of IDC and lower frequency of ILC and DCIS, owing probably to a different risk profile. Use of hospital information systems and establishment of population based cancer registry is required to have accurate and detailed local data. Promotion of breast health awareness and better health care system is required to decrease the burden of advanced disease.

The Relationship between Serum Lipids and Breast Cancer in Libya

Background: Carcinoma breast is one of the major surgical problems in Libya, particularly in younger female subjects. Since it is a commonly encountered health risk, it is important to know the etiology and associated related factors of breast cancer in Libya. There are conflicting reports regarding the association between the dietary lipids and serum lipid profiles and breast cancer. It is a fact that local dietary habits, environmental factors along with genetic predisposition play a role in the evolution of breast cancer. The present study was undertaken to identify whether there is such an association between alterations in lipid profile in carcinoma breast in a local Libyan subjects. Material and methods: A total of 40 patients with various stages of breast cancer who were being treated at the department of surgery, 7th October hospital, Benghazi, Libya during 2009 and 2010 were recruited in the present study. Twenty one healthy volunteers were included as controls. These patients were categorized according to age, pre or post menopausal status and body mass index with their respective controls. Serum lipid profile was performed in all the cases and control groups using fasting blood samples. Total cholesterol, HDL-cholesterol and Triglycerides were measured by standard kit methods and LDL cholesterol was calculated using Fried Wald’s formula. Results: Serum total cholesterol and HDL cholesterol have been observed to be significantly elevated in patients with carcinoma breast when compared with those of controls (p=0.0046 and 0.004 respectively). However, the serum levels of LDL cholesterol and triglycerides did not show any significant alteration between that of the cases studied and the controls (p=0.42 and 0.092 respectively). In the case of premenopausal women, there is a significant rise of total cholesterol (p=0.0186) and HDL cholesterol (p=0.0031) whereas serum triglycerides (p=0.335) and LDL cholesterol (p=0.2617) had not shown any statistically significant variation. Furthermore, in the postmenopausal group, there is a significant elevation of serum triglycerides (p=0.0094), total cholesterol (p=0.0238) and HDL cholesterol (p=0.0457) but LDL cholesterol had not shown any significant variation. There is a significant variation between the triglyceride levels of postmenopausal women and the premenopausal women (p=0.0298). Conclusion: This preliminary study has shown a significant alteration in serum lipid profile of breast cancer patients in the local Libyan female population. The interesting observation of high levels of HDL cholesterol in the patients needs further evaluation by extending the investigation further on and also extending the study on larger study group. Postmenopausal women have shown an increase in serum triglycerides levels, with an increase observed in serum total cholesterol and HDL cholesterol levels when compared to that of premenopausal women

Metabolic, Health and Lifestyle Profiling of Breast Cancer Radiotherapy Patients and the Risk of Developing Fatigue

Background: Fatigue is commonly reported by cancer patients. In some instances it can persist after treatment is completed. In order to develop effective treatment strategies it is important to understand the mechanisms underlying the development of fatigue and to be able to predict those that may be at greatest risk of experiencing fatigue during and following treatment. The current paper examines predisposing factors for fatigue including altered fatty acid homeostasis in a cohort of breast cancer radiotherapy patients. Methodology: Patients had undergone breast-conserving surgery and adjuvant breast irradiation. Prior to radiotherapy the patients were free from significant fatigue. Levels of fatigue were determined prior to and following radiotherapy using the Functional Assessment of Cancer Therapy fatigue subscale. Plasma fatty acid levels, urinary and plasma amino acid levels, blood biochemistry factors and general health and lifestyle characteristics were assessed. Results: Following radiotherapy, significant fatigue affected approximately one third of the 26 patients and these subjects were then assigned to the fatigued cohort. Univariate analysis revealed that higher levels of the fatty acids myristic acid and eicosadienoic acid were present for the fatigued cohort prior to radiotherapy. Multivariate analysis also revealed that fatty acid homeostasis was altered between the fatigued and non-fatigued groups at baseline. Orthogonal partial least squares discriminant analysis of the general health, lifestyle and metabolic data revealed that the fatigued and non-fatigued patients could be clustered into two clearly separate groups. Conclusions: The results supported the proposition that the fatigued patients had an underlying metabolic homeostasis which may predispose them to the development of fatigue. Biochemical and general health profiling of breast cancer patients has the potential to identify those at most risk of developing significant fatigue following radiotherapy.

Solid phase microextraction, mass spectrometry and metabolomic approaches for detection of potential urinary cancer biomarkers—A powerful strategy for breast cancer diagnosis

A sensitive assay to identify volatile organic metabolites (VOMs) as biomarkers that can accurately diagnose the onset of breast cancer using non-invasively collected clinical specimens is ideal for early detection. Therefore the aim of this study was to establish the urinary metabolomic profile of breast cancer patients and healthy individuals (control group) and to explore the VOMs as potential biomarkers in breast cancer diagnosis at early stage. Solid-phase microextraction (SPME) using CAR/PDMS sorbent combined with gas chromatography–mass spectrometry was applied to obtain metabolomic information patterns of 26 breast cancer patients and 21 healthy individuals (controls). A total of seventy-nine VOMs, belonging to distinct chemical classes, were detected and identified in control and breast cancer groups. Ketones and sulfur compounds were the chemical classes with highest contribution for both groups. Results showed that excretion values of 6 VOMs among the total of 79 detected were found to be statistically different (p<0.05). A significant increase in the peak area of (−)-4-carene, 3-heptanone, 1,2,4-trimethylbenzene, 2-methoxythiophene and phenol, in VOMs of cancer patients relatively to controls was observed. Statiscally significant lower abundances of dimethyl disulfide were found in cancer patients. Bioanalytical data were submitted to multivariate statistics [principal component analysis (PCA)], in order to visualize clusters of cases and to detect the VOMs that are able to differentiate cancer patients from healthy individuals. Very good discrimination within breast cancer and control groups was achieved. Nevertheless, a deep study using a larger number of patients must be carried out to confirm the results.

P1-02-07: Epithelial-Mesenchymal Transition Correlated with Serum Cytokine Profiling in Breast Cancer Patients.

Abstract Background: Inflammation contributes to the increased invasiveness and poor prognosis in breast cancer (BC) patients. Specifically, the expression of the proinflammatory cytokines interleukin-6 (IL-6), tumor necrosis factor alpha (TNFα) and interleukin-1 (IL-1) have all been linked to increased invasiveness and poor prognosis. Interestingly, the increased invasiveness was associated with an increase in the acquisition of markers of epithelial-mesenchymal transition (EMT). Therefore, we determined whether the levels of circulating proinflammatory cytokines (IL-1, IL-6, TNFα) and antiinflammatory cytokines (IL10) were correlated with the induction of EMT transcription factors (TFs), Snail1, Zeb1, Twist1, in breast cancer patients. Materials and Methods: From two laboratory-based ongoing studies at the MD Anderson Cancer Center, 41 BC patients were assessed for EMT-TFs in circulating CD45-ve cells (EMT-CTCs) and for serum proinflammatory cytokines before starting any treatment. 32 of 41 patients assessed for EMT had metastatic BC. EMT-CTCs were detected by qRT-PCR for the EMT-TFs Snail1, Zeb1 and Twist1 (Mego 2011; PMID 21387303) and serum cytokines were measured by Luminex bead array assay (MILLIPLEX™ MAP Human Cytokine/Chemokine Panel). Cytokine serum concentrations were compared with the median cytokine levels of healthy donors (HD). We examined the association of serum cytokines above the median HD levels and the presence of EMT-CTCs by non-parametric Mann-Whitney test with a statistical significance for p&amp;lt;.05. Results: Of the 41 patients assessed for both serum cytokines and EMT-CTCs, 14 (34%) were positive for at least one EMT-TF, including 3 of 9 (33%) patients with no-metastatic BC and 11 of 32 (34%) patients with metastatic BC. We found that serum levels of IL1a, IL2, TGFα, and TNFβ in patients that were above the median levels of HD sera were higher in patients with EMT-CTCs in the blood (higher IL1a concentration in patients with over expression of Snail1, Zeb1, and Twist1; IL2 with Zeb1; TGFα with Snail1; TNFβ with Zeb1, and Twist1). Further, the higher ratio of proinflammatory/anti-inflammatory cytokines, was associated with the presence of at least one EMT-TF, e.g., IL8/IL10 (p=.005) and TNFα/IL10 (p=.037). Discussion: Patients with proinflammatory cytokine (IL1a, IL2, TGFα, and TNFβ) levels above the median levels of HD or who had a predominantly proinflammatory cytokine profile were more likely to have at least one EMT-TF in their blood. These data are consistent with the hypothesis that proinflammatory cytokines promote EMT, which may be involved in tumor aggressiveness and disease progression. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-02-07.

Primary Study of Lymph Node Metastasis‐Related Serum Biomarkers in Breast Cancer

The aim of this study was to detect the pretreatment serum protein profiles of breast cancer patients by mass spectrometry (MS) to screen candidate tumor biomarkers, which will supply a simple, accurate, and minimally invasive method to predict the axillary lymph node metastasis of breast cancer. We used magnetic bead-based weak cation-exchange chromatography followed by matrix-assisted laser desorption and ionization time-of-flight MS to detect proteins in the sera of 54 cases of axillary node-negative breast cancer, 47 cases of axillary node-positive breast cancer, and 101 healthy controls. The protein profiles were analyzed to screen tumor biomarkers and lymph node metastasis-associated proteins to establish and verify a diagnostic model. Comparison of the protein profiles between the two cancer groups resulted in a total of 111 discriminate m/z peaks that were associated with breast cancer. Furthermore, 40 discriminate m/z peaks were detected between breast cancer patients with and without axillary node metastases. Four protein m/z peaks at 5,643, 4,651, 2,377, and 2,240 were used to construct a diagnosis model, and cross-validation indicated that breast cancer with and without axillary node metastasis was identified with 87.04% sensitivity (47/54), 87.23% specificity (41/47), and 87.13% accuracy (88/101). These proteins could potentially be used as predictive biomarkers to distinguish between breast cancer patients with or without lymph node metastasis.

Diurnal cortisol profile in breast cancer patients before and during treatment with Viscum album (Iscador ® P) for 3 or 6 months

Diurnal cortisol profile in breast cancer patients before and during treatment with Viscum album (Iscador ® P) for 3 or 6 months

Oxidative stress and hematological profiles of advanced breast cancer patients subjected to paclitaxel or doxorubicin chemotherapy

Several adverse effects of chemotherapy treatments have been described, and most of these effects are associated with direct interactions between blood cells and indirect effects generated during the oxidative metabolism of antineoplastic drugs. In this study we evaluated the oxidative systemic status and hematological profiles of breast cancer patients with advanced ductal infiltrative carcinoma treated with doxorubicin (DOX) or paclitaxel (PTX) within 1 h after chemotherapy. Blood analyses included evaluation of hemogram, pro-oxidative markers, and antioxidant status. The results showed that advanced breast cancer diseased (AD) patients without previous chemotherapy presented anemia and high oxidative stress status characterized by elevated levels of lipid peroxidation and nitric oxide, and reduced catalase activity when compared with controls. DOX-treated patients exhibited increased anemia and reduced antioxidant status, which was revealed by decreases in reduced glutathione levels and the total antioxidant capacity of plasma; however, these changes did not lead to further increases in lipid peroxidation or carbonyl proteins when compared with the AD group. PTX-treated patients also showed increased anemia, lactate dehydrogenase leakage, and enhanced lipid peroxidation. These data reveal for the first time that patients subjected to chemotherapy with DOX or PTX present immediate systemic oxidative stress and red blood cell oxidative injury with anemia development. These findings provide a new perspective on the systemic redox state of AD and patients subjected to chemotherapy regarding oxidative stress enhancement and its possible involvement in the aggravation of chronic anemia.