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Sample records for breast cancer biomarker

  1. Breast Cancer Biomarkers Based on Nipple and Fine Needle Aspirates

    National Research Council Canada - National Science Library

    Russo, Irma H

    2005-01-01

    ... of the cytological normal breast epithelium of women at high risk for breast cancer. This signature will serve as an intermediate biomarker for evaluating the response of the breast to novel chemopreventive agents...

  2. Do serum biomarkers really measure breast cancer?

    Directory of Open Access Journals (Sweden)

    Yurkovetsky Zoya

    2009-05-01

    Full Text Available Abstract Background Because screening mammography for breast cancer is less effective for premenopausal women, we investigated the feasibility of a diagnostic blood test using serum proteins. Methods This study used a set of 98 serum proteins and chose diagnostically relevant subsets via various feature-selection techniques. Because of significant noise in the data set, we applied iterated Bayesian model averaging to account for model selection uncertainty and to improve generalization performance. We assessed generalization performance using leave-one-out cross-validation (LOOCV and receiver operating characteristic (ROC curve analysis. Results The classifiers were able to distinguish normal tissue from breast cancer with a classification performance of AUC = 0.82 ± 0.04 with the proteins MIF, MMP-9, and MPO. The classifiers distinguished normal tissue from benign lesions similarly at AUC = 0.80 ± 0.05. However, the serum proteins of benign and malignant lesions were indistinguishable (AUC = 0.55 ± 0.06. The classification tasks of normal vs. cancer and normal vs. benign selected the same top feature: MIF, which suggests that the biomarkers indicated inflammatory response rather than cancer. Conclusion Overall, the selected serum proteins showed moderate ability for detecting lesions. However, they are probably more indicative of secondary effects such as inflammation rather than specific for malignancy.

  3. Development of Nanomechanical Sensors for Breast Cancer Biomarkers

    National Research Council Canada - National Science Library

    Erramilli, Shyamsunder

    2006-01-01

    ... to similar breakthroughs in array sensors for biomolecules of interest to the breast cancer community. Nanotechnology can meet the need for high throughput, sensitive methods for rapidly recording biomarker profiles of tumors in individual patients...

  4. tRNAs as Biomarkers and Regulators for Breast Cancer

    Science.gov (United States)

    2010-08-01

    metastasized to bones). Cell Line ER PgR HER2 Tumor Type Tissue Source Tumorigenic Tumor Classification MCF10A - - Fibrocystic Disease Mammary...TITLE: tRNAs as Biomarkers and Regulators for Breast Cancer PRINCIPAL INVESTIGATOR: Tao Pan, Ph.D...tRNAs as Biomarkers and Regulators for Breast Cancer 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-07-1-0595 5c. PROGRAM ELEMENT NUMBER

  5. Aberrantly methylated DNA as a biomarker in breast cancer

    DEFF Research Database (Denmark)

    Kristiansen, Søren; Jørgensen, Lars Mønster; Guldberg, Per

    2013-01-01

    Aberrant DNA hypermethylation at gene promoters is a frequent event in human breast cancer. Recent genome-wide studies have identified hundreds of genes that exhibit differential methylation between breast cancer cells and normal breast tissue. Due to the tumor-specific nature of DNA...... hypermethylation events, their use as tumor biomarkers is usually not hampered by analytical signals from normal cells, which is a general problem for existing protein tumor markers used for clinical assessment of breast cancer. There is accumulating evidence that DNA-methylation changes in breast cancer patients...... occur early during tumorigenesis. This may open up for effective screening, and analysis of blood or nipple aspirate may later help in diagnosing breast cancer. As a more detailed molecular characterization of different types of breast cancer becomes available, the ability to divide patients...

  6. Urinary metalloproteinases: noninvasive biomarkers for breast cancer risk assessment

    DEFF Research Database (Denmark)

    Pories, Susan E; Zurakowski, David; Roy, Roopali

    2008-01-01

    Matrix metalloproteinases (MMP) and a disintegrin and metalloprotease 12 (ADAM 12) can be detected in the urine of breast cancer patients and provide independent prediction of disease status. To evaluate the potential of urinary metalloproteinases as biomarkers to predict breast cancer risk status...... as biomarkers in the identification of women at increased risk of developing breast cancer......., urine samples from women with known risk marker lesions, atypical hyperplasia and lobular carcinoma in situ (LCIS), were analyzed. Urine samples were obtained from 148 women: 44 women with atypical hyperplasia, 24 women with LCIS, and 80 healthy controls. MMP analysis was done using gelatin zymography...

  7. Biomarkers of the Metabolic Syndrome and Breast Cancer Prognosis

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Qiu-Li; Xu, Wang-Hong, E-mail: mtao@buffalo.edu [Department of Epidemiology, School of Public Health, Fudan University, Shanghai 200032 (China); Tao, Meng-Hua, E-mail: mtao@buffalo.edu [Department of Social and Preventive Medicine, School of Public Health and Health Professions, University at Buffalo, Buffalo, NY 14214 (United States)

    2010-04-28

    In spite of its public health importance, our understanding of the mechanisms of breast carcinogenesis and progress is still evolving. The metabolic syndrome (MS) is a constellation of biochemical abnormalities including visceral adiposity, hyperglycemia, hyperinsulinemia, dyslipidemia and high blood pressure. The components of the MS have all been related to late-stage disease and even to a poor prognosis of breast cancer through multiple interacting mechanisms. In this review, we aim to present a summary of recent advances in the understanding of the contribution of the MS to breast cancer with the emphasis on the role of biomarkers of the MS in the prognosis of breast cancer.

  8. Biomarkers of the Metabolic Syndrome and Breast Cancer Prognosis

    Directory of Open Access Journals (Sweden)

    Meng-Hua Tao

    2010-04-01

    Full Text Available In spite of its public health importance, our understanding of the mechanisms of breast carcinogenesis and progress is still evolving. The metabolic syndrome (MS is a constellation of biochemical abnormalities including visceral adiposity, hyperglycemia, hyperinsulinemia, dyslipidemia and high blood pressure. The components of the MS have all been related to late-stage disease and even to a poor prognosis of breast cancer through multiple interacting mechanisms. In this review, we aim to present a summary of recent advances in the understanding of the contribution of the MS to breast cancer with the emphasis on the role of biomarkers of the MS in the prognosis of breast cancer.

  9. MicroRNAs as Novel Biomarkers for Breast Cancer

    Directory of Open Access Journals (Sweden)

    H. M. Heneghan

    2010-01-01

    Full Text Available Breast cancer is a complex phenotypically diverse genetic disease, involving a variety of changes in gene expression and structure. Recent advances in molecular profiling technology have made great progress in unravelling the molecular taxonomy of breast cancer, which has shed new light on the aetiology of the disease and also heralded great potential for the development of novel biomarkers and therapeutic targets. Mi(croRNAs are a contemporary class of small noncoding endogenous RNA molecules, generating great excitement in the clinical and scientific communities. The recent discovery that miRNA expression is frequently dysregulated in cancer has uncovered an entirely new repertoire of molecular factors upstream of gene expression, which warrants extensive investigation to further elucidate their precise role in malignancy. We present a comprehensive and timely review of the role of miRNAs in cancer: addressing miRNA function, their putative role as oncogenes or tumor suppressors, with a particular emphasis on breast cancer throughout. We discuss the recent discovery of quantifiable circulating cancer-associated miRNAs, which heralds immense potential for their use as novel minimally invasive biomarkers for breast and other cancers. Finally, we comment on the potential role of miRNAs in breast cancer management, particularly in improving current prognostic tools and achieving the goal of individualized cancer treatment.

  10. Automated assessment of bilateral breast volume asymmetry as a breast cancer biomarker during mammographic screening

    Energy Technology Data Exchange (ETDEWEB)

    Williams, Alex C [ORNL; Hitt, Austin N [ORNL; Voisin, Sophie [ORNL; Tourassi, Georgia [ORNL

    2013-01-01

    The biological concept of bilateral symmetry as a marker of developmental stability and good health is well established. Although most individuals deviate slightly from perfect symmetry, humans are essentially considered bilaterally symmetrical. Consequently, increased fluctuating asymmetry of paired structures could be an indicator of disease. There are several published studies linking bilateral breast size asymmetry with increased breast cancer risk. These studies were based on radiologists manual measurements of breast size from mammographic images. We aim to develop a computerized technique to assess fluctuating breast volume asymmetry in screening mammograms and investigate whether it correlates with the presence of breast cancer. Using a large database of screening mammograms with known ground truth we applied automated breast region segmentation and automated breast size measurements in CC and MLO views using three well established methods. All three methods confirmed that indeed patients with breast cancer have statistically significantly higher fluctuating asymmetry of their breast volumes. However, statistically significant difference between patients with cancer and benign lesions was observed only for the MLO views. The study suggests that automated assessment of global bilateral asymmetry could serve as a breast cancer risk biomarker for women undergoing mammographic screening. Such biomarker could be used to alert radiologists or computer-assisted detection (CAD) systems to exercise increased vigilance if higher than normal cancer risk is suspected.

  11. Breast cancer biomarkers predict weight loss after gastric bypass surgery

    Directory of Open Access Journals (Sweden)

    Sauter Edward R

    2012-01-01

    Full Text Available Abstract Background Obesity has long been associated with postmenopausal breast cancer risk and more recently with premenopausal breast cancer risk. We previously observed that nipple aspirate fluid (n levels of prostate specific antigen (PSA were associated with obesity. Serum (s levels of adiponectin are lower in women with higher body mass index (BMI and with breast cancer. We conducted a prospective study of obese women who underwent gastric bypass surgery to determine: 1 change in n- and s-adiponectin and nPSA after surgery and 2 if biomarker change is related to change in BMI. Samples (30-s, 28-n and BMI were obtained from women 0, 3, 6 and 12 months after surgery. Findings There was a significant increase after surgery in pre- but not postmenopausal women at all time points in s-adiponectin and at 3 and 6 months in n-adiponectin. Low n-PSA and high s-adiponectin values were highly correlated with decrease in BMI from baseline. Conclusions Adiponectin increases locally in the breast and systemically in premenopausal women after gastric bypass. s-adiponectin in pre- and nPSA in postmenopausal women correlated with greater weight loss. This study provides preliminary evidence for biologic markers to predict weight loss after gastric bypass surgery.

  12. Epigenetic Biomarkers of Breast Cancer Risk: Across the Breast Cancer Prevention Continuum

    Science.gov (United States)

    McDonald, Jasmine A.; Wu, Hui Chen; Eng, Sybil; Santella, Regina M.

    2017-01-01

    Epigenetic biomarkers, such as DNA methylation, can increase cancer risk through altering gene expression. The Cancer Genome Atlas (TCGA) Network has demonstrated breast cancer-specific DNA methylation signatures. DNA methylation signatures measured at the time of diagnosis may prove important for treatment options and in predicting disease-free and overall survival (tertiary prevention). DNA methylation measurement in cell free DNA may also be useful in improving early detection by measuring tumor DNA released into the blood (secondary prevention). Most evidence evaluating the use of DNA methylation markers in tertiary and secondary prevention efforts for breast cancer comes from studies that are cross-sectional or retrospective with limited corresponding epidemiologic data, raising concerns about temporality. Few prospective studies exist that are large enough to address whether DNA methylation markers add to the prediction of tertiary and secondary outcomes over and beyond standard clinical measures. Determining the role of epigenetic biomarkers in primary prevention can help in identifying modifiable pathways for targeting interventions and reducing disease incidence. The potential is great for DNA methylation markers to improve cancer outcomes across the prevention continuum. Large, prospective epidemiological studies will provide essential evidence of the overall utility of adding these markers to primary prevention efforts, screening, and clinical care. PMID:26987530

  13. Image Based Biomarker of Breast Cancer Risk: Analysis of Risk Disparity Among Minority Populations

    Science.gov (United States)

    2014-03-01

    visibility of microcalcification (MCs) in clinical images is of critical importance for breast imaging, as MCs can be the only sign of early cancer . To...AD_________________ Award Number: W81XWH-09-1-0062 TITLE: Image Based Biomarker of Breast Cancer ...Report 3. DATES COVERED (From - To) – 14 1212 4. TITLE AND SUBTITLE Image Based Biomarker of Breast Cancer Risk: 5a. CONTRACT

  14. Identification of New Serum Biomarkers for Early Breast Cancer Diagnosis and Prognosis Using Lipid Microarrays

    National Research Council Canada - National Science Library

    Du, Guangwei

    2008-01-01

    Breast cancer is the most common form of cancer among women. Compared with other serum polypeptides, autoantibodies have many appealing features as biomarkers including sensitivity, stability, and easy detection...

  15. Putative Biomarkers and Targets of Estrogen Receptor Negative Human Breast Cancer

    Directory of Open Access Journals (Sweden)

    Stephen W. Byers

    2011-07-01

    Full Text Available Breast cancer is a progressive and potentially fatal disease that affects women of all ages. Like all progressive diseases, early and reliable diagnosis is the key for successful treatment and annihilation. Biomarkers serve as indicators of pathological, physiological, or pharmacological processes. Her2/neu, CA15.3, estrogen receptor (ER, progesterone receptor (PR, and cytokeratins are biomarkers that have been approved by the Food and Drug Administration for disease diagnosis, prognosis, and therapy selection. The structural and functional complexity of protein biomarkers and the heterogeneity of the breast cancer pathology present challenges to the scientific community. Here we review estrogen receptor-related putative breast cancer biomarkers, including those of putative breast cancer stem cells, a minor population of estrogen receptor negative tumor cells that retain the stem cell property of self renewal. We also review a few promising cytoskeleton targets for ER alpha negative breast cancer.

  16. Detecting blood-based biomarkers in metastatic breast cancer : A systematic review of their current status and clinical utility

    NARCIS (Netherlands)

    Berghuis, A.M. Sofie; Koffijberg, Hendrik; Prakash, Jai; Terstappen, Leon W.M.M.; Ijzerman, Maarten J.

    2017-01-01

    Reviews on circulating biomarkers in breast cancer usually focus on one single biomarker or a selective group of biomarkers. An overview summarizing the discovery and evaluation of all blood-based biomarkers in metastatic breast cancer is lacking. This systematic review aims to identify the

  17. Plasma Biomarker Profiles Differ Depending on Breast Cancer Subtype but RANTES is Consistently Increased

    Energy Technology Data Exchange (ETDEWEB)

    Gonzales, Rachel M.; Daly, Don S.; Tan, Ruimin; Marks, Jeffrey R.; Zangar, Richard C.

    2011-07-01

    Background: Current biomarkers for breast cancer have little potential for detection. We determined if breast cancer subtypes influence circulating protein biomarkers. Methods: A sandwich-ELISA microarray platform was used to evaluate 23 candidate biomarkers in plasma samples that were obtained from subjects with either benign breast disease or invasive breast cancer. All plasma samples were collected at the time of biopsy, after a referral due to a suspicious screen (e.g., mammography). Cancer samples were evaluated based on breast cancer subtypes, as defined by the HER2 and estrogen receptor statuses. Results: Ten proteins were statistically altered in at least one breast cancer subtype, including four epidermal growth factor receptor ligands, two matrix metalloproteases, two cytokines, and two angiogenic factors. Only one cytokine, RANTES, was significantly increased (P<0.01 for each analysis) in all four subtypes, with areas under receiver operating characteristic curves (AUC) that ranged from 0.76 to 0.82, depending on cancer subtype. The best AUC values were observed for analyses that combined data from multiple biomarkers, with values ranging from 0.70 to 0.99, depending on the cancer subtype. Although the results for RANTES are consistent with previous publications, the multi-assay results need to be validated in independent sample sets. Conclusions: Different breast cancer subtypes produce distinct biomarker profiles, and circulating protein biomarkers have potential to differentiate between true and false positive screens for breast cancer. Impact: Subtype-specific biomarker panels may be useful for detecting breast cancer or as an adjunct assay to improve the accuracy of current screening methods.

  18. Exercise, weight loss and biomarkers for breast cancer risk

    NARCIS (Netherlands)

    Gemert, W.A.M. van

    2015-01-01

    Background: Postmenopausal breast cancer is the most prevalent cancer in Western women. There are several known risk factors for postmenopausal breast cancer of which few are lifestyle-related and, thereby, modifiable. These risk factors provide an opportunity for primary prevention. In this thesis,

  19. Biomarkers in Tissue Samples From Patients With Newly Diagnosed Breast Cancer Treated With Zoledronic Acid

    Science.gov (United States)

    2017-06-07

    Estrogen Receptor-positive Breast Cancer; Invasive Ductal Breast Carcinoma; Progesterone Receptor-positive Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer

  20. Tropomyosin-1, A Putative Tumor-Suppressor and a Biomarker of Human Breast Cancer

    Science.gov (United States)

    2004-10-01

    cDNA. Lobular carcinoma - 2 A polyclonal pan-TM antibody that recognizes multiple TM Phyllodes tumor - 1 Not determined from the initial pathology...AD Award Number: DAMD17-98-1-8162 TITLE: Tropomyosin-1, A Putative Tumor -Suppressor and a Biomarker of Human Breast Cancer PRINCIPAL INVESTIGATOR...4. TITLE AND SUBTITLE 5. FUNDING NUMBERS Tropomyosin-l, A Putative Tumor -Suppressor and a Biomarker DAMD17-98-1-8162 of Human Breast Cancer 6. A UTHOR

  1. Serum atrial natriuretic peptide: a suspected biomarker of breast cancer

    Directory of Open Access Journals (Sweden)

    Maha E. Houssen

    2017-03-01

    Full Text Available Aim of the study : To assess serum levels of ANP in breast cancer female patients and its relationship to metastasis and some clinical parameters among those patients. Material and methods : One hundred breast cancer patients with and without metastasis along with 20 healthy closely matched controls, were enrolled in the present cross sectional study. Background: To assess the serum levels of atrial natriuretic peptide in breast cancer Serum levels of ANP were assessed using ELISA. Results : Mean serum levels of ANP breast cancer patients (13.9 ±10.1 ng/ml were significantly elevated compared to healthy control group (2.2 ±1.3 ng/ml (p < 0.001. The metastatic breast cancer patients showed significant elevated ANP levels (17.1 ±8.9 ng/ml compared to non-metastatic group (6.4 ±8.8 ng/ml p < 0.001. Within the metastatic group significant difference was detected between de novo metastatic, under follow-up, under hormonal control and locally advanced group (p = 0.007. Conclusions : This study showed significant elevated levels of ANP in the serum of metastatic breast cancer patients compared to non-metastatic patients. Within the metastatic group the lowest levels were detected in metastatic breast Cancer under hormonal treatment either tamoxifen or aromatase inhibitor.

  2. Can Prostate Specific Antigen Be Used as New Biomarker for Early Diagnosis of Breast Cancer?

    Directory of Open Access Journals (Sweden)

    Seyed Mostafa Shiryazdi

    2015-09-01

    Conclusion: Plasma PSA level is not a reliable biomarker to diagnose breast cancer, though regarding existing scientific evidence, more comprehensive studies are required to consider other features of malignant samples so as to evaluate the role of PSA in differentiating breast neoplastic lesions in a more meticulous way based on the degree of tumor differentiation.

  3. CCNA2 Is a Prognostic Biomarker for ER+ Breast Cancer and Tamoxifen Resistance

    OpenAIRE

    Gao, Tian; Han, Yong; Yu, Ling; Ao, Sheng; Li, Ziyu; Ji, Jiafu

    2014-01-01

    Identification of effective prognostic biomarkers and targets are of crucial importance to the management of estrogen receptor positive (ER+) breast cancer. CCNA2 (also known as CyclinA2) belongs to the highly conserved cyclin family and is significantly overexpressed in various cancer types. In this study, we demonstrated that CCNA2 had significant predictive power in distant metastasis free survival, disease free survival, recurrence free survival and overall survival of ER+ breast cancer p...

  4. Early Detection of Breast Cancer Using Posttranslationally Modified Biomarkers

    Science.gov (United States)

    2013-09-01

    oxidative damage and loss of mlsmatcb re- pair enzymes during breast carcinogenesis. Eur J Cancer 42. (2006); 2653-2659. [6] J. Marx . Cancer research...Glycophenotype of prostatic carcinomas. Folia Histochem. Cytobiol. 2010, 48 (4), 637−645. (5) Mariano, A.; Di Carlo , A.; Santonastaso, C.; Oliva, A

  5. Identification of annexin II as a novel secretory biomarker for breast cancer.

    Science.gov (United States)

    Jeon, You Rim; Kim, Sun Young; Lee, Eun Jeong; Kim, Yong Nyun; Noh, Dong-Young; Park, So Yeon; Moon, Aree

    2013-11-01

    Early prediction of metastatic breast cancer is important for improvement of prognosis and survival rate. The present study aimed to identify secreted protein biomarkers for detection of invasive breast cancer. To this end, we performed a comparative proteomic analysis by a combination of 2DE and MALDI-TOF MS analysis of conditioned media from invasive H-Ras MCF10A human breast epithelial cells and noninvasive MCF10A and N-Ras MCF10A cells. We identified a list of 25 proteins that were strongly detected in media of H-Ras MCF10A and focused on annexin II, which was shown to be involved in cell motility. Invasive triple-negative human breast carcinoma cells, Hs578T, and MDA-MB-231, showed increased levels of annexin II in media, demonstrating that secretion of annexin II correlated well with the invasive phenotype of cells. We demonstrated a crucial role of annexin II in breast cell invasion/migration and actin cytoskeleton reorganization required for filopodia formation. Annexin II levels in the plasma samples and breast cancer tissues of breast cancer patients were significantly higher than those of normal groups, providing a clinical relevance to our in vitro findings. Taken together, we identified annexin II as a novel secretory biomarker candidate for invasive breast cancer, especially estrogen receptor-negative breast cancer. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. High expressions of LDHA and AMPK as prognostic biomarkers for breast cancer.

    Science.gov (United States)

    Huang, Xiaojia; Li, Xing; Xie, Xinhua; Ye, Feng; Chen, Bo; Song, Cailu; Tang, Hailin; Xie, Xiaoming

    2016-12-01

    The purpose of this study was to investigate the potential correlation between lactate dehydrogenase A (LDHA) and AMP-activated protein kinase (AMPK) and their clinicopathologic significance in breast cancer. Western blot and qRT-PCR were used to detect the expression levels of LDHA and AMPK in eight breast cancer lines and eight breast cancer tissues. In addition, LDHA and AMPK were detected by immunohistochemistry (IHC) using breast cancer tissue microarrays (TMAs) of 112 patients. The association between LDHA and AMPK expression levels was statistically analyzed. So were the prognostic roles and clinicopathologic significances in breast cancer. The expression levels of LDHA and AMPK were relatively higher in triple-negative breast cancer (TNBC) cell lines than in non-triple-negative breast cancer (NTNBC) cell lines. LDHA and AMPK were also further up-regulated in TNBC tissues than in NTNBC tissues. Correlation analysis showed a positive correlation between LDHA and AMPK expression levels. Expression of LDHA and AMPK were significantly correlated with TNM stage, distant metastasis, Ki67 status and survival outcomes of patients. Patients with both positive expression of LDHA and AMPK showed shorter overall survival (OS) and disease-free survival (DFS). These findings improve our understanding of the expression pattern of LDHA and AMPK in breast cancer and clarify the role of LDHA and AMPK as promising prognostic biomarkers for breast cancer. Copyright © 2016. Published by Elsevier Ltd.

  7. Identification of microRNAs in Nipple Discharge as Potential Diagnostic Biomarkers for Breast Cancer.

    Science.gov (United States)

    Zhang, Kai; Zhao, Song; Wang, Qing; Yang, Hsin-Sheng; Zhu, Jiang; Ma, Rong

    2015-12-01

    Intraductal breast cancer is generally difficult to diagnose because of a lack of an efficient method for detection. The purpose of this study was to reveal and validate the differential expression of microRNAs (miRNAs) in nipple discharge from intraductal papilloma patients and identify miRNAs as novel potential biomarkers for primary breast cancer. Nipple discharge samples were collected from three intraductal carcinoma breast cancer patients and three intraductal papilloma patients. The initial screening of miRNA expression was performed with an Axon GenePix 4000B microarray scanner using a novel approach to label miRNAs. The expression levels of the miRNAs selected from the initial screening were further examined by quantitative real-time polymerase chain reaction (qRT-PCR) in 21 validation samples (8 carcinomas and 13 benign tumors). An independent t test was used to detect significant correlations between the miRNA expression levels and breast cancer. Microarray profiling demonstrated that three miRNAs were markedly up-regulated and three miRNAs were down-regulated in the intraductal carcinoma breast cancer patients compared to the papilloma group. The qRT-PCR analysis further verified that four miRNAs (miR-4484, miR-K12-5-5p, miR-3646, and miR-4732-5p) might serve as potential tumor biomarkers for breast cancer detection. The novel approach of using a microarray scanner is applicable for studying biomarkers in nipple discharge containing small amounts of miRNA. miRNAs could serve as potential tumor biomarkers that can assist in breast cancer screening. Up-regulation of miR-4484, miR-K12-5-5p, and miR-3646 in nipple discharge may be a predictor of malignant breast cancer.

  8. Circulating microRNAs as specific biomarkers for breast cancer detection.

    Directory of Open Access Journals (Sweden)

    Enders K O Ng

    Full Text Available BACKGROUND: We previously showed microRNAs (miRNAs in plasma are potential biomarkers for colorectal cancer detection. Here, we aimed to develop specific blood-based miRNA assay for breast cancer detection. METHODOLOGY/PRINCIPAL FINDINGS: TaqMan-based miRNA profiling was performed in tumor, adjacent non-tumor, corresponding plasma from breast cancer patients, and plasma from matched healthy controls. All putative markers identified were verified in a training set of breast cancer patients. Selected markers were validated in a case-control cohort of 170 breast cancer patients, 100 controls, and 95 other types of cancers and then blindly validated in an independent set of 70 breast cancer patients and 50 healthy controls. Profiling results showed 8 miRNAs were concordantly up-regulated and 1 miRNA was concordantly down-regulated in both plasma and tumor tissue of breast cancer patients. Of the 8 up-regulated miRNAs, only 3 were significantly elevated (p<0.0001 before surgery and reduced after surgery in the training set. Results from the validation cohort showed that a combination of miR-145 and miR-451 was the best biomarker (p<0.0001 in discriminating breast cancer from healthy controls and all other types of cancers. In the blind validation, these plasma markers yielded Receiver Operating Characteristic (ROC curve area of 0.931. The positive predictive value was 88% and the negative predictive value was 92%. Altered levels of these miRNAs in plasma have been detected not only in advanced stages but also early stages of tumors. The positive predictive value for ductal carcinoma in situ (DCIS cases was 96%. CONCLUSIONS: These results suggested that these circulating miRNAs could be a potential specific biomarker for breast cancer screening.

  9. Digital image analysis outperforms manual biomarker assessment in breast cancer

    DEFF Research Database (Denmark)

    Stålhammar, Gustav; Fuentes Martinez, Nelson; Lippert, Michael

    2016-01-01

    immunohistochemical stains act as surrogate markers for these subtypes. Thus, congruence of surrogate markers and gene expression tests is of utmost importance. In this study, 3 cohorts of primary breast cancer specimens (total n=436) with up to 28 years of survival data were scored for Ki67, ER, PR, and HER2 status...

  10. Androgen receptor as a mediator and biomarker of radioresistance in triple-negative breast cancer.

    Science.gov (United States)

    Speers, Corey; Zhao, Shuang G; Chandler, Ben; Liu, Meilan; Wilder-Romans, Kari; Olsen, Eric; Nyati, Shyam; Ritter, Cassandra; Alluri, Prasanna G; Kothari, Vishal; Hayes, Daniel F; Lawrence, Theodore S; Spratt, Daniel E; Wahl, Daniel R; Pierce, Lori J; Feng, Felix Y

    2017-01-01

    Increased rates of locoregional recurrence have been observed in triple-negative breast cancer despite chemotherapy and radiation therapy. Thus, approaches that combine therapies for radiosensitization in triple-negative breast cancer are critically needed. We characterized the radiation therapy response of 21 breast cancer cell lines and paired this radiation response data with high-throughput drug screen data to identify androgen receptor as a top target for radiosensitization. Our radiosensitizer screen nominated bicalutamide as the drug most effective in treating radiation therapy-resistant breast cancer cell lines. We subsequently evaluated the expression of androgen receptor in >2100 human breast tumor samples and 51 breast cancer cell lines and found significant heterogeneity in androgen receptor expression with enrichment at the protein and RNA level in triple-negative breast cancer. There was a strong correlation between androgen receptor RNA and protein expression across all breast cancer subtypes (R(2) = 0.72, p triple-negative breast cancer, expression of androgen receptor above the median was associated with increased risk of locoregional recurrence after radiation therapy (hazard ratio for locoregional recurrence 2.9-3.2)) in two independent data sets, but there was no difference in locoregional recurrence in triple-negative breast cancer patients not treated with radiation therapy when stratified by androgen receptor expression. In multivariable analysis, androgen receptor expression was most significantly associated with worse local recurrence-free survival after radiation therapy (hazard ratio of 3.58) suggesting that androgen receptor expression may be a biomarker of radiation response in triple-negative breast cancer. Inhibition of androgen receptor with MDV3100 (enzalutamide) induced radiation sensitivity (enhancement ratios of 1.22-1.60) in androgen receptor-positive triple-negative breast cancer lines, but did not affect androgen

  11. Association between changes in fat distribution and biomarkers for breast cancer

    NARCIS (Netherlands)

    van Gemert, Willemijn A.M.; Monninkhof, Evelyn M.; May, Anne M.; Elias, Sjoerd G.; Van Der Palen, Job; Veldhuis, Wouter B.; Stapper, Maaike; Stellato, Rebecca K.; Schuit, Jantine A.; Peeters, Petra H.

    2017-01-01

    We assessed the associations between changes in total and abdominal fat and changes in biomarkers for breast cancer risk using data of the SHAPE-2 trial. In the SHAPE-2 trial, 243 postmenopausal overweight women were included. The intervention in this trial consisted of 5-6 kg weight loss either by

  12. Association between changes in fat distribution and biomarkers for breast cancer

    NARCIS (Netherlands)

    van Gemert, Willemijn A; Monninkhof, Evelyn M; May, Anne M; Elias, Sjoerd G; van der Palen, Job; Veldhuis, Wouter; Stapper, Maaike; Stellato, Rebecca K; Schuit, A.J.; Peeters, Petra H

    We assessed the associations between changes in total and abdominal fat and changes in biomarkers for breast cancer risk using data of the SHAPE-2 trial. In the SHAPE-2 trial, 243 postmenopausal overweight women were included. The intervention in this trial consisted of 5-6 kg weight loss either by

  13. Early diagnostic protein biomarkers for breast cancer: how far have we come?

    NARCIS (Netherlands)

    Opstal - van Winden, A.W.J.|info:eu-repo/dai/nl/355613239; Vermeulen, R.C.H.|info:eu-repo/dai/nl/216532620; Peeters, P.H.M.; Beijnen, J.H.|info:eu-repo/dai/nl/071919570; van Gils, C.H.

    2012-01-01

    Many studies have used surface-enhanced laser desorption/ionization time-of-flight mass spectrometry or matrix-assisted laser desorption/ionization time-of-flight mass spectrometry to search for blood-based proteins that are related to the presence of breast cancer. We review the biomarkers

  14. Can Biomarker Assessment on Circulating Tumor Cells Help Direct Therapy in Metastatic Breast Cancer?

    Energy Technology Data Exchange (ETDEWEB)

    Turner, Natalie [Sandro Pitigliani Medical Oncology Department, Prato Hospital, Istituto Toscano Tumori, Via Ugo Foscolo, Prato, PO 59100 (Italy); Pestrin, Marta [Sandro Pitigliani Medical Oncology Department, Prato Hospital, Istituto Toscano Tumori, Via Ugo Foscolo, Prato, PO 59100 (Italy); Translational Research Laboratory, Prato Hospital, Via Ugo Foscolo, Prato, PO 59100 (Italy); Galardi, Francesca; De Luca, Francesca [Translational Research Laboratory, Prato Hospital, Via Ugo Foscolo, Prato, PO 59100 (Italy); Malorni, Luca [Sandro Pitigliani Medical Oncology Department, Prato Hospital, Istituto Toscano Tumori, Via Ugo Foscolo, Prato, PO 59100 (Italy); Translational Research Laboratory, Prato Hospital, Via Ugo Foscolo, Prato, PO 59100 (Italy); Di Leo, Angelo, E-mail: adileo@usl4.toscana.it [Sandro Pitigliani Medical Oncology Department, Prato Hospital, Istituto Toscano Tumori, Via Ugo Foscolo, Prato, PO 59100 (Italy)

    2014-03-25

    Circulating tumor cell (CTC) count has prognostic significance in metastatic breast cancer, but the predictive utility of CTCs is uncertain. Molecular studies on CTCs have often been limited by a low number of CTCs isolated from a high background of leukocytes. Improved enrichment techniques are now allowing molecular characterisation of single CTCs, whereby molecular markers on single CTCs may provide a real-time assessment of tumor biomarker status from a blood test or “liquid biopsy”, potentially negating the need for a more invasive tissue biopsy. The predictive ability of CTC biomarker analysis has predominantly been assessed in relation to HER2, with variable and inconclusive results. Limited data exist for other biomarkers, such as the estrogen receptor. In addition to the need to define and validate the most accurate and reproducible method for CTC molecular analysis, the clinical relevance of biomarkers, including gain of HER2 on CTC after HER2 negative primary breast cancer, remains uncertain. This review summarises the currently available data relating to biomarker evaluation on CTCs and its role in directing management in metastatic breast cancer, discusses limitations, and outlines measures that may enable future development of this approach.

  15. Identification and validation of oncologic miRNA biomarkers for luminal A-like breast cancer.

    Directory of Open Access Journals (Sweden)

    Ailbhe M McDermott

    Full Text Available INTRODUCTION: Breast cancer is a common disease with distinct tumor subtypes phenotypically characterized by ER and HER2/neu receptor status. MiRNAs play regulatory roles in tumor initiation and progression, and altered miRNA expression has been demonstrated in a variety of cancer states presenting the potential for exploitation as cancer biomarkers. Blood provides an excellent medium for biomarker discovery. This study investigated systemic miRNAs differentially expressed in Luminal A-like (ER+PR+HER2/neu- breast cancer and their effectiveness as oncologic biomarkers in the clinical setting. METHODS: Blood samples were prospectively collected from patients with Luminal A-like breast cancer (n = 54 and controls (n = 56. RNA was extracted, reverse transcribed and subjected to microarray analysis (n = 10 Luminal A-like; n = 10 Control. Differentially expressed miRNAs were identified by artificial neural network (ANN data-mining algorithms. Expression of specific miRNAs was validated by RQ-PCR (n = 44 Luminal A; n = 46 Control and potential relationships between circulating miRNA levels and clinicopathological features of breast cancer were investigated. RESULTS: Microarray analysis identified 76 differentially expressed miRNAs. ANN revealed 10 miRNAs for further analysis (miR-19b, miR-29a, miR-93, miR-181a, miR-182, miR-223, miR-301a, miR-423-5p, miR-486-5 and miR-652. The biomarker potential of 4 miRNAs (miR-29a, miR-181a, miR-223 and miR-652 was confirmed by RQ-PCR, with significantly reduced expression in blood of women with Luminal A-like breast tumors compared to healthy controls (p = 0.001, 0.004, 0.009 and 0.004 respectively. Binary logistic regression confirmed that combination of 3 of these miRNAs (miR-29a, miR-181a and miR-652 could reliably differentiate between cancers and controls with an AUC of 0.80. CONCLUSION: This study provides insight into the underlying molecular portrait of Luminal A-like breast

  16. Beyond circulating microRNA biomarkers: Urinary microRNAs in ovarian and breast cancer.

    Science.gov (United States)

    Gasparri, Maria Luisa; Casorelli, Assunta; Bardhi, Erlisa; Besharat, Aris Raad; Savone, Delia; Ruscito, Ilary; Farooqi, Ammad Ahmad; Papadia, Andrea; Mueller, Michael David; Ferretti, Elisabetta; Benedetti Panici, Pierluigi

    2017-05-01

    Breast cancer is the most common malignancy in women worldwide, and ovarian cancer is the most lethal gynecological malignancy. Women carrying a BRCA1/2 mutation have a very high lifetime risk of developing breast and ovarian cancer. The only effective risk-reducing strategy in BRCA-mutated women is a prophylactic surgery with bilateral mastectomy and bilateral salpingo-oophorectomy. However, many women are reluctant to undergo these prophylactic surgeries due to a consequent mutilated body perception, unfulfilled family planning, and precocious menopause. In these patients, an effective screening strategy is available only for breast cancer, but it only consists in close radiological exams with a significant burden for the health system and a significant distress to the patients. No biomarkers have been shown to effectively detect breast and ovarian cancer at an early stage. MicroRNAs (miRNAs) are key regulatory molecules operating in a post-transcriptional regulation of gene expression. Aberrant expression of miRNAs has been documented in several pathological conditions, including solid tumors, suggesting their involvement in tumorigenesis. miRNAs can be detected in blood and urine and could be used as biomarkers in solid tumors. Encouraging results are emerging in gynecological malignancy as well, and suggest a different pattern of expression of miRNAs in biological fluids of breast and ovarian cancer patients as compared to healthy control. Aim of this study is to highlight the role of the urinary miRNAs which are specifically associated with cancer and to investigate their role in early diagnosis and in determining the prognosis in breast and ovarian cancer.

  17. Hypermethylation of BRCA1 gene: implication for prognostic biomarker and therapeutic target in sporadic primary triple-negative breast cancer.

    Science.gov (United States)

    Zhu, X; Shan, L; Wang, F; Wang, J; Wang, F; Shen, G; Liu, X; Wang, B; Yuan, Y; Ying, J; Yang, H

    2015-04-01

    Paraffin sections from 239 cases of surgical resected mammary gland carcinomas were assessed to determine the role of BRCA1 gene methylation in sporadic triple-negative breast cancer and to evaluate the relationship between BRCA1 gene methylation and clinicopathologic features of triple-negative breast cancer in the National Cancer Center, China. Diagnostic tissues collected from patients received mastectomy in the National Cancer Center from January 1, 1999 to December 31, 2008 were reviewed. Tissue microarrays were constructed using 239 triple-negative breast cancer cases and stained with estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, cytokeratin 5/6, and epidermal growth factor receptor. Methylation status of the BRCA1 promoter was measured by methylation-specific PCR and analyzed against clinicopathologic characteristics, subtypes, and prognosis using standard statistical methods. Among the 239 triple-negative breast cancer cases, 137 (57.3 %) showed methylation of the BRCA1. According to the immunohistochemistry results, triple-negative breast cancer cases were classified into basal-like breast cancer (60.7 %) and non-basal-like breast cancer (39.3 %). The frequency of BRCA1 methylation was significantly higher in basal-like breast cancer subtype (71.7 %) than the non-basal subtype (35.1 %). Thus, BRCA1 methylation is statistically significantly correlated with basal-like breast cancer subtype (p breast cancer. Here we demonstrated that epigenetic alteration of key tumor suppressor gene can be a promising biomarker for the prognosis of triple-negative breast cancer/basal-like breast cancer. Specifically our finding revealed that BRCA1 methylation is closely associated with a significant decrease in overall survival and disease-free survival, highlighting BRCA1 promoter methylation as promising and powerful biomarkers for effect and better prognosis of DNA damaging agents for triple-negative breast cancer/basal-like breast

  18. Aurora kinase B is important for antiestrogen resistant cell growth and a potential biomarker for tamoxifen resistant breast cancer

    DEFF Research Database (Denmark)

    Larsen, Sarah L; Yde, Christina W.; Laenkholm, Anne-Vibeke

    2015-01-01

    BACKGROUND: Resistance to antiestrogen therapy is a major clinical challenge in the treatment of estrogen receptor α (ER)-positive breast cancer. The aim of the study was to explore the growth promoting pathways of antiestrogen resistant breast cancer cells to identify biomarkers and novel treatm...

  19. BIOMARKER IDENTIFICATION IN BREAST CANCER: BETA-ADRENERGIC RECEPTOR SIGNALING AND PATHWAYS TO THERAPEUTIC RESPONSE

    Directory of Open Access Journals (Sweden)

    Liana E. Kafetzopoulou

    2013-03-01

    Full Text Available Recent preclinical studies have associated beta-adrenergic receptor (β-AR signaling with breast cancer pathways such as progression and metastasis. These findings have been supported by clinical and epidemiological studies which examined the effect of beta-blocker therapy on breast cancer metastasis, recurrence and mortality. Results from these studies have provided initial evidence for the inhibition of cell migration in breast cancer by beta-blockers and have introduced the beta-adrenergic receptor pathways as a target for therapy. This paper analyzes gene expression profiles in breast cancer patients, utilising Artificial Neural Networks (ANNs to identify molecular signatures corresponding to possible disease management pathways and biomarker treatment strategies associated with beta-2-adrenergic receptor (ADRB2 cell signaling. The adrenergic receptor relationship to cancer is investigated in order to validate the results of recent studies that suggest the use of beta-blockers for breast cancer therapy. A panel of genes is identified which has previously been reported to play an important role in cancer and also to be involved in the beta-adrenergic receptor signaling.

  20. Biomarker identification in breast cancer: Beta-adrenergic receptor signaling and pathways to therapeutic response.

    Science.gov (United States)

    Kafetzopoulou, Liana E; Boocock, David J; Dhondalay, Gopal Krishna R; Powe, Desmond G; Ball, Graham R

    2013-01-01

    Recent preclinical studies have associated beta-adrenergic receptor (β-AR) signaling with breast cancer pathways such as progression and metastasis. These findings have been supported by clinical and epidemiological studies which examined the effect of beta-blocker therapy on breast cancer metastasis, recurrence and mortality. Results from these studies have provided initial evidence for the inhibition of cell migration in breast cancer by beta-blockers and have introduced the beta-adrenergic receptor pathways as a target for therapy. This paper analyzes gene expression profiles in breast cancer patients, utilising Artificial Neural Networks (ANNs) to identify molecular signatures corresponding to possible disease management pathways and biomarker treatment strategies associated with beta-2-adrenergic receptor (ADRB2) cell signaling. The adrenergic receptor relationship to cancer is investigated in order to validate the results of recent studies that suggest the use of beta-blockers for breast cancer therapy. A panel of genes is identified which has previously been reported to play an important role in cancer and also to be involved in the beta-adrenergic receptor signaling.

  1. Improved prediction of breast cancer outcome by identifying heterogeneous biomarkers.

    Science.gov (United States)

    Choi, Jonghwan; Park, Sanghyun; Yoon, Youngmi; Ahn, Jaegyoon

    2017-11-15

    Identification of genes that can be used to predict prognosis in patients with cancer is important in that it can lead to improved therapy, and can also promote our understanding of tumor progression on the molecular level. One of the common but fundamental problems that render identification of prognostic genes and prediction of cancer outcomes difficult is the heterogeneity of patient samples. To reduce the effect of sample heterogeneity, we clustered data samples using K-means algorithm and applied modified PageRank to functional interaction (FI) networks weighted using gene expression values of samples in each cluster. Hub genes among resulting prioritized genes were selected as biomarkers to predict the prognosis of samples. This process outperformed traditional feature selection methods as well as several network-based prognostic gene selection methods when applied to Random Forest. We were able to find many cluster-specific prognostic genes for each dataset. Functional study showed that distinct biological processes were enriched in each cluster, which seems to reflect different aspect of tumor progression or oncogenesis among distinct patient groups. Taken together, these results provide support for the hypothesis that our approach can effectively identify heterogeneous prognostic genes, and these are complementary to each other, improving prediction accuracy. https://github.com/mathcom/CPR. jgahn@inu.ac.kr. Supplementary data are available at Bioinformatics online.

  2. Detecting Blood-Based Biomarkers in Metastatic Breast Cancer: A Systematic Review of Their Current Status and Clinical Utility

    Directory of Open Access Journals (Sweden)

    A. M. Sofie Berghuis

    2017-02-01

    Full Text Available Reviews on circulating biomarkers in breast cancer usually focus on one single biomarker or a selective group of biomarkers. An overview summarizing the discovery and evaluation of all blood-based biomarkers in metastatic breast cancer is lacking. This systematic review aims to identify the available evidence of known blood-based biomarkers in metastatic breast cancer, regarding their clinical utility and state-of-the-art position in the validation process. The initial search yielded 1078 original studies, of which 420 were assessed for eligibility. A total of 320 studies were included in the final synthesis. A Development, Evaluation and Application Chart (DEAC of all biomarkers was developed. Most studies focus on identifying new biomarkers and search for relations between these biomarkers and traditional molecular characteristics. Biomarkers are usually investigated in only one study (68.8%. Only 9.8% of all biomarkers was investigated in more than five studies. Circulating tumor cells, gene expression within tumor cells and the concentration of secreted proteins are the most frequently investigated biomarkers in liquid biopsies. However, there is a lack of studies focusing on identifying the clinical utility of these biomarkers, by which the additional value still seems to be limited according to the investigated evidence.

  3. Identification of Nucleobindin-2 as a Potential Biomarker for Breast Cancer Metastasis Using iTRAQ-based Quantitative Proteomic Analysis.

    Science.gov (United States)

    Zeng, Liang; Zhong, Jingmin; He, Guangchun; Li, Fangjun; Li, Jing; Zhou, Wen; Liu, Wenbin; Zhang, Yun; Huang, Sanqian; Liu, Zhihong; Deng, Xiyun

    2017-01-01

    Metastasis is a lethal step in the progression of breast cancer. None of the metastasis-associated biomarkers identified up to now has a definite prognostic value in breast cancer patients. This study was designed to identify biomarkers for breast cancer metastasis and predictors of the prognosis of breast cancer patients. The differentially expressed proteins between 23 paired primary breast tumor and metastatic lymph nodes were identified by quantitative iTRAQ proteomic analysis. Immunohistochemistry was applied to locate and assess the expression of NUCB2 in paired primary breast tumor and metastatic lymph node tissues (n = 106). The relationship between NUCB2 expression and the clinicopathological characteristics of breast cancer patients (n = 189) were analyzed by χ(2) test. Kaplan-Meier analysis and Cox hazard regression analysis were utilized to investigate the relationship between its expression and prognosis of breast cancer patients. The iTRAQ proteomic results showed that 4,837 confidential proteins were identified, 643 of which were differentially expressed in the primary breast cancer tissues and the paired metastatic lymph nodes. NUCB2 protein was found decreased in paired metastatic lymph nodes (P = 0.000), with the positive expression rate being 82% in primary breast cancer tissues and 47% in paired metastatic lymph nodes, respectively. According to Kaplan-Meier analysis, the overall survival time of patients with positive expression of NUCB2 protein were shorter than those with negative NUCB2 expression (P = 0.004). Cox regression model suggested that NUCB2 was a risk factor of breast cancer patients (P = 0.045, RR = 1.854). We conclude that NUCB2 can be used as a potential biomarker for breast cancer metastasis and a prognostic predictor of breast cancer patients.

  4. Molecular Biomarkers for Prediction of Targeted Therapy Response in Metastatic Breast Cancer: Trick or Treat?

    Science.gov (United States)

    Toss, Angela; Venturelli, Marta; Peterle, Chiara; Piacentini, Federico; Cascinu, Stefano; Cortesi, Laura

    2017-01-04

    In recent years, the study of genomic alterations and protein expression involved in the pathways of breast cancer carcinogenesis has provided an increasing number of targets for drugs development in the setting of metastatic breast cancer (i.e., trastuzumab, everolimus, palbociclib, etc.) significantly improving the prognosis of this disease. These drugs target specific molecular abnormalities that confer a survival advantage to cancer cells. On these bases, emerging evidence from clinical trials provided increasing proof that the genetic landscape of any tumor may dictate its sensitivity or resistance profile to specific agents and some studies have already showed that tumors treated with therapies matched with their molecular alterations obtain higher objective response rates and longer survival. Predictive molecular biomarkers may optimize the selection of effective therapies, thus reducing treatment costs and side effects. This review offers an overview of the main molecular pathways involved in breast carcinogenesis, the targeted therapies developed to inhibit these pathways, the principal mechanisms of resistance and, finally, the molecular biomarkers that, to date, are demonstrated in clinical trials to predict response/resistance to targeted treatments in metastatic breast cancer.

  5. Molecular Biomarkers for Prediction of Targeted Therapy Response in Metastatic Breast Cancer: Trick or Treat?

    Directory of Open Access Journals (Sweden)

    Angela Toss

    2017-01-01

    Full Text Available In recent years, the study of genomic alterations and protein expression involved in the pathways of breast cancer carcinogenesis has provided an increasing number of targets for drugs development in the setting of metastatic breast cancer (i.e., trastuzumab, everolimus, palbociclib, etc. significantly improving the prognosis of this disease. These drugs target specific molecular abnormalities that confer a survival advantage to cancer cells. On these bases, emerging evidence from clinical trials provided increasing proof that the genetic landscape of any tumor may dictate its sensitivity or resistance profile to specific agents and some studies have already showed that tumors treated with therapies matched with their molecular alterations obtain higher objective response rates and longer survival. Predictive molecular biomarkers may optimize the selection of effective therapies, thus reducing treatment costs and side effects. This review offers an overview of the main molecular pathways involved in breast carcinogenesis, the targeted therapies developed to inhibit these pathways, the principal mechanisms of resistance and, finally, the molecular biomarkers that, to date, are demonstrated in clinical trials to predict response/resistance to targeted treatments in metastatic breast cancer.

  6. [Search for breast cancer-related biomarker proteins for drug discovery].

    Science.gov (United States)

    Nagano, Kazuya

    2010-12-01

    The identification of biomarkers is a promising approach for the diagnosis and effective therapy of cancer. In particular, disease proteomics is a potentially useful method for identifying such biomarkers. However, very few biomarker proteins for drug development have been discovered using this approach. The main difficulty is to efficiently select potential biomarkers from the many candidate proteins identified by the proteomics approach. To circumvent this problem, we have developed "antibody proteomics technology" that can screen for biomarker proteins by isolating antibodies against each candidate in a rapid and comprehensive manner. Here, we applied "antibody proteomics technology" to breast cancer-related biomarker discovery and evaluated the utility of this novel technology. Cell extracts derived from breast tumor cells (SKBR3) and normal cells (184A1) were analyzed by two-dimensional differential gel electrophoresis (2D-DIGE) to identify proteins over-expressed in the tumor cells. Candidate proteins were extracted from the gel pieces, immobilized onto a nitrocellulose membrane using a dot blot apparatus and then used as target antigens in scFv-phage enrichment and selection. Following this in vitro phage selection procedure, scFvs binding to 21 different over-expressed proteins in tumor cells were successfully isolated within several weeks. The expression profiles of the identified proteins were then determined by tissue microarray analysis using the scFv-phages. Consequently, we identified three breast tumor-specific proteins. Our data demonstrates the utility of an antibody proteomics system for discovering and validating tumor-related proteins in pharmaceutical proteomics. Currently, we are analyzing the functions of these proteins to use them as diagnostic markers or therapeutic targets.

  7. Differential profiling of breast cancer plasma proteome by isotope-coded affinity tagging method reveals biotinidase as a breast cancer biomarker

    Directory of Open Access Journals (Sweden)

    Yu Myeong-Hee

    2010-03-01

    Full Text Available Abstract Background Breast cancer is one of the leading causes of women's death worldwide. It is important to discover a reliable biomarker for the detection of breast cancer. Plasma is the most ideal source for cancer biomarker discovery since many cells cross-communicate through the secretion of soluble proteins into blood. Methods Plasma proteomes obtained from 6 breast cancer patients and 6 normal healthy women were analyzed by using the isotope-coded affinity tag (ICAT labeling approach and tandem mass spectrometry. All the plasma samples used were depleted of highly abundant 6 plasma proteins by immune-affinity column chromatography before ICAT labeling. Several proteins showing differential abundance level were selected based on literature searches and their specificity to the commercially available antibodies, and then verified by immunoblot assays. Results A total of 155 proteins were identified and quantified by ICAT method. Among them, 33 proteins showed abundance changes by more than 1.5-fold between the plasmas of breast cancer patients and healthy women. We chose 5 proteins for the follow-up confirmation in the individual plasma samples using immunoblot assay. Four proteins, α1-acid glycoprotein 2, monocyte differentiation antigen CD14, biotinidase (BTD, and glutathione peroxidase 3, showed similar abundance ratio to ICAT result. Using a blind set of plasmas obtained from 21 breast cancer patients and 21 normal healthy controls, we confirmed that BTD was significantly down-regulated in breast cancer plasma (Wilcoxon rank-sum test, p = 0.002. BTD levels were lowered in all cancer grades (I-IV except cancer grade zero. The area under the receiver operating characteristic curve of BTD was 0.78. Estrogen receptor status (p = 0.940 and progesterone receptor status (p = 0.440 were not associated with the plasma BTD levels. Conclusions Our study suggests that BTD is a potential serological biomarker for the detection of breast cancer.

  8. Chromosome 1q21.3 amplification is a trackable biomarker and actionable target for breast cancer recurrence

    DEFF Research Database (Denmark)

    Goh, Jian Yuan; Feng, Min; Wang, Wenyu

    2017-01-01

    Tumor recurrence remains the main reason for breast cancer-associated mortality, and there are unmet clinical demands for the discovery of new biomarkers and development of treatment solutions to benefit patients with breast cancer at high risk of recurrence. Here we report the identification...... of chromosomal copy-number amplification at 1q21.3 that is enriched in subpopulations of breast cancer cells bearing characteristics of tumor-initiating cells (TICs) and that strongly associates with breast cancer recurrence. Amplification is present in ∼10-30% of primary tumors but in more than 70% of recurrent...... tumors, regardless of breast cancer subtype. Detection of amplification in cell-free DNA (cfDNA) from blood is strongly associated with early relapse in patients with breast cancer and could also be used to track the emergence of tumor resistance to chemotherapy. We further show that 1q21.3-encoded S100...

  9. Expression Patterns of Biomarkers in Primary Tumors and Corresponding Metastases in Breast Cancer

    DEFF Research Database (Denmark)

    Kümler, Iben; Balslev, Eva; Knop, Ann S

    2016-01-01

    Tumor heterogeneity has been shown for several cancers including breast cancer (BC). Despite the fact that expression of tumor markers may change throughout the metastatic process, rebiopsies at the time of recurrence are still not performed routinely at all institutions. The aims of the study were......, and Ki-67 in 110 paired samples of primary BC and corresponding asynchronous metastases. We found discordant expressions in primary tumor and metastasis for all biomarkers, although only significant for Ki-67. Changes in the expression profile of the metastatic lesions would have altered treatment...

  10. Autoantibody to tumor antigen, alpha 2-HS glycoprotein: a novel biomarker of breast cancer screening and diagnosis.

    Science.gov (United States)

    Yi, Jae Kyo; Chang, Jong Wook; Han, Wonshik; Lee, Jong Won; Ko, Eunyoung; Kim, Dong Hyun; Bae, Ji-Yeon; Yu, Jonghan; Lee, Cheolju; Yu, Myeong-Hee; Noh, Dong-Young

    2009-05-01

    We sought to identify a new serum biomarker for breast cancer screening and diagnosis using stepwise proteomic analysis of sera from breast cancer patients to detect the presence of autoantibodies that react with urinary protein. Two-dimensional immunoblotting was done for screening autoimmunogenic tumor antigens in the urine of breast cancer patients. Reactive spots were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Among urinary proteins separated by two-dimensional electrophoresis, 13 spots showed strong reactivity with pooled sera from breast cancer patients or control sera. By mass spectrometry, we identified alpha 2-HS glycoprotein (AHSG) as a tumor antigen. Peripheral blood was obtained from 81 women diagnosed with breast cancer before surgery and 73 female donors without evidence of any malignancy for the individual analysis. In one-dimensional Western blot analysis, AHSG autoantibody was detected in 64 of 81 breast cancer patients (79.1%) and in 7 of 73 controls (9.6%). The sensitivity of this test in breast cancer patients was 79.0%. Our results suggest that AHSG and anti-AHSG autoantibody may be useful serum biomarkers for breast cancer screening and diagnosis.

  11. Identification of Developmental Endothelial Locus-1 on Circulating Extracellular Vesicles as a Novel Biomarker for Early Breast Cancer Detection.

    Science.gov (United States)

    Moon, Pyong-Gon; Lee, Jeong-Eun; Cho, Young-Eun; Lee, Soo Jung; Jung, Jin Hyang; Chae, Yee Soo; Bae, Han-Ik; Kim, Young-Bum; Kim, In-San; Park, Ho Yong; Baek, Moon-Chang

    2016-04-01

    Currently, there are no molecular biomarkers for the early detection of breast cancer. This study focused on identifying surface proteins found on circulating extracellular vesicles (EVs) for detecting early-stage breast cancer. Circulating EVs, isolated from the plasma of 10 patients with breast cancer (stages I and II) and 5 healthy controls, were analyzed using LC-MS/MS. Developmental endothelial locus-1 protein (Del-1) was selected as a candidate biomarker. Two different ELISAs were used to measure Del-1 in plasma samples from healthy controls (n= 81), patients with breast cancer (n= 269), breast cancer patients after surgical resection (n= 50), patients with benign breast tumors (n= 64), and patients with noncancerous diseases (n= 98) in two cohorts. Plasma Del-1 levels were significantly higher (Pbreast cancer than in all controls and returned to almost normal after tumor removal. The diagnostic accuracy of Del-1 was AUC, 0.961 [95% confidence interval (CI), 0.924-0.983], sensitivity of 94.70%, and specificity of 86.36% in test cohort and 0.968 (0.933-0.988), 92.31%, and 86.62% in validation cohort for early-stage breast cancer by one type of ELISA. Furthermore, Del-1 maintained diagnostic accuracy for patients with early-stage breast cancer using the other type of ELISA [0.946 (0.905-0.972), 90.90%, and 77.14% in the test cohort; 0.943 (0.900-0.971), 89.23%, and 80.99% in the validation cohort]. Del-1 on circulating EVs is a promising marker to improve identification of patients with early-stage breast cancer and distinguish breast cancer from benign breast tumors and noncancerous diseases. ©2015 American Association for Cancer Research.

  12. Promoter Hypermethylation of the ATM Gene as a Novel Biomarker for Breast Cancer

    Science.gov (United States)

    Begam, Nasrin; Jamil, Kaiser; Raju, Suryanarayana G

    2017-11-26

    Background: Breast cancer may be induced by activation of protooncogenes to oncogenes and in many cases inactivation of tumor suppressor genes. Ataxia telangiectasia mutated (ATM) is an important tumor suppressor gene which plays central roles in the maintenance of genomic integrity by activating cell cycle checkpoints and promoting repair of double-strand breaks of DNA. In breast cancer, decrease ATM expression correlates with a poor outcome; however, the molecular mechanisms underlying downregulation are still unclear. Promoter hypermethylation may contribute in downregulation. Hence the present investigation was designed to evaluate promoter methylation and expression of the ATM gene in breast cancer cases, and to determine links with clinical and demographic manifestations, in a South Indian population. Methods: Tumor biopsy samples were collected from 50 pathologically confirmed sporadic breast cancer cases. DNA was isolated from tumor and adjacent non-tumorous regions, and sodium bisulfite conversion and methylation-specific PCR were performed using MS-PCR primers for the ATM promoter region. In addition, ATM mRNA expression was also analyzed for all samples using real-time PCR. Results: Fifty eight percent (58%) of cancer tissue samples showed promoter hypermethylation for the ATM gene, in contrast to only 4.44% of normal tissues (p= 0.0001). Furthermore, ATM promoter methylation was positively associated with age (p = 0.01), tumor size (p=0.045) and advanced stage of disease i.e. stages III and IV (p =0.019). An association between promoter hypermethylation and lower expression of ATM mRNA was also found (p=0.035). Conclusion: We report for the first time that promoter hypermethylation of ATM gene may be useful as a potential new biomarker for breast cancer, especially in the relatively young patients. Creative Commons Attribution License

  13. Triple negative breast cancer chemosensitivity and chemoresistance: current advances in biomarkers indentification.

    Science.gov (United States)

    Guestini, Fouzia; McNamara, Keely May; Ishida, Takanori; Sasano, Hironobu

    2016-06-01

    Triple negative breast cancer (TNBC) is a heterogeneous clinicopathological entity constituting approximately 15 - 20% of all breast cancer (BC) patients. It shows high recurrence rate and poor prognosis. At this juncture, because of the lack of specific targeted therapies available and the development in patients of resistance to some therapeutic agents, clinical and translational settings have gained importance over the past decades. The development of novel, safe and effective alternatives for the treatment of TNBC are in high demand. Therefore, this review aims to summarize the state of the art of TNBC, its current therapies and potential therapeutic targets. In particular, focus is put on recent advances regarding the identification of emerging biomarkers as prognostic and/or predictive markers, including surrogate markers for molecular tumor subtyping and identifying potential responders to new therapies. Effective development of informative markers could constitute an important armamentarium tool for identifying appropriate therapies to challenge the aggressiveness of TNBC.

  14. The Relevance of Epigenetic Biomarkers for Breast Cancer and Obesity for Personalised Treatment in Public Healthcare: A Systematic Review

    OpenAIRE

    Andrea Goettler; Haslberger, Alexander G.; Elena Ambrosino

    2016-01-01

    Background: Personalised medicine has gained attention as a result of the advances of genomic research in the last decade. This includes the rise in epigenetic research, which focuses on the environmental influences on the genome and examines biomarkers that might be useful for cancer therapy. This study investigates the epigenetic biomarkers for breast cancer and its risk factor, obesity, and evaluates their relevance for global public health. Methods: A systematic search of articles pub...

  15. Activated Leukocyte Cell Adhesion Molecule: a Novel Biomarker for Breast Cancer

    Science.gov (United States)

    Kulasingam, Vathany; Zheng, Yingye; Soosaipillai, Antoninus; Leon, Antonette E.; Gion, Massimo; Diamandis, Eleftherios P.

    2013-01-01

    Activated leukocyte cell adhesion molecule (ALCAM) has been implicated in tumorigenesis. Our goal was to examine the levels of ALCAM, in addition to the classical breast cancer tumor markers carbohydrate antigen 15-3 (CA15-3) and carcinoembryonic antigen (CEA), in serum by quantitative ELISA for diagnosis in breast cancer patients. The three proteins were measured in serum of 100 healthy women, 50 healthy men and 150 breast carcinoma patients. The diagnostic sensitivity and specificity of the tests were calculated and the association of serum marker concentrations with various clinicopathologic variables was examined using nonparametric Kruskal-Wallis tests. Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic performance of the biomarkers. ALCAM, with area under the curve (AUC) of 0.78 [95% CI: 0.73, 0.84] outperformed CA15-3 (AUC= 0.70 [95% CI: 0.64, 0.76]) and CEA (AUC= 0.63 [95% CI: 0.56, 0.70]). The incremental values of AUC for ALCAM over that for CA15-3 were statistically significant (Delong test, p breast cancer and may have value for disease diagnosis. PMID:19322904

  16. Proteomic Analysis of Urine to Identify Breast Cancer Biomarker Candidates Using a Label-Free LC-MS/MS Approach.

    Directory of Open Access Journals (Sweden)

    Julia Beretov

    Full Text Available Breast cancer is a complex heterogeneous disease and is a leading cause of death in women. Early diagnosis and monitoring progression of breast cancer are important for improving prognosis. The aim of this study was to identify protein biomarkers in urine for early screening detection and monitoring invasive breast cancer progression.We performed a comparative proteomic analysis using ion count relative quantification label free LC-MS/MS analysis of urine from breast cancer patients (n = 20 and healthy control women (n = 20.Unbiased label free LC-MS/MS-based proteomics was used to provide a profile of abundant proteins in the biological system of breast cancer patients. Data analysis revealed 59 urinary proteins that were significantly different in breast cancer patients compared to the normal control subjects (p3. Thirty-six urinary proteins were exclusively found in specific breast cancer stages, with 24 increasing and 12 decreasing in their abundance. Amongst the 59 significant urinary proteins identified, a list of 13 novel up-regulated proteins were revealed that may be used to detect breast cancer. These include stage specific markers associated with pre-invasive breast cancer in the ductal carcinoma in-situ (DCIS samples (Leucine LRC36, MAST4 and Uncharacterized protein CI131, early invasive breast cancer (DYH8, HBA, PEPA, uncharacterized protein C4orf14 (CD014, filaggrin and MMRN2 and metastatic breast cancer (AGRIN, NEGR1, FIBA and Keratin KIC10. Preliminary validation of 3 potential markers (ECM1, MAST4 and filaggrin identified was performed in breast cancer cell lines by Western blotting. One potential marker MAST4 was further validated in human breast cancer tissues as well as individual human breast cancer urine samples with immunohistochemistry and Western blotting, respectively.Our results indicate that urine is a useful non-invasive source of biomarkers and the profile patterns (biomarkers identified, have potential for clinical

  17. Proteomic Analysis of Urine to Identify Breast Cancer Biomarker Candidates Using a Label-Free LC-MS/MS Approach.

    Science.gov (United States)

    Beretov, Julia; Wasinger, Valerie C; Millar, Ewan K A; Schwartz, Peter; Graham, Peter H; Li, Yong

    2015-01-01

    Breast cancer is a complex heterogeneous disease and is a leading cause of death in women. Early diagnosis and monitoring progression of breast cancer are important for improving prognosis. The aim of this study was to identify protein biomarkers in urine for early screening detection and monitoring invasive breast cancer progression. We performed a comparative proteomic analysis using ion count relative quantification label free LC-MS/MS analysis of urine from breast cancer patients (n = 20) and healthy control women (n = 20). Unbiased label free LC-MS/MS-based proteomics was used to provide a profile of abundant proteins in the biological system of breast cancer patients. Data analysis revealed 59 urinary proteins that were significantly different in breast cancer patients compared to the normal control subjects (p3). Thirty-six urinary proteins were exclusively found in specific breast cancer stages, with 24 increasing and 12 decreasing in their abundance. Amongst the 59 significant urinary proteins identified, a list of 13 novel up-regulated proteins were revealed that may be used to detect breast cancer. These include stage specific markers associated with pre-invasive breast cancer in the ductal carcinoma in-situ (DCIS) samples (Leucine LRC36, MAST4 and Uncharacterized protein CI131), early invasive breast cancer (DYH8, HBA, PEPA, uncharacterized protein C4orf14 (CD014), filaggrin and MMRN2) and metastatic breast cancer (AGRIN, NEGR1, FIBA and Keratin KIC10). Preliminary validation of 3 potential markers (ECM1, MAST4 and filaggrin) identified was performed in breast cancer cell lines by Western blotting. One potential marker MAST4 was further validated in human breast cancer tissues as well as individual human breast cancer urine samples with immunohistochemistry and Western blotting, respectively. Our results indicate that urine is a useful non-invasive source of biomarkers and the profile patterns (biomarkers) identified, have potential for clinical use in

  18. Absolute Quantification of Choline-Related Biomarkers in Breast Cancer Biopsies by Liquid Chromatography Electrospray Ionization Mass Spectrometry

    Directory of Open Access Journals (Sweden)

    Maria Chiara Mimmi

    2013-01-01

    Full Text Available It has been repeatedly demonstrated that choline metabolism is altered in a wide variety of cancers. In breast tumours, the choline metabolite profile is characterized by an elevation of phosphocholine and total choline-compounds. This pattern is increasingly being exploited as biomarker in cancer diagnosis.

  19. Synthesis and characterization of a HAp-based biomarker with controlled drug release for breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    González, Maykel [Dept. of Molecular Engineering of Materials, Center of Applied Physics and Advanced Technology, National Autonomous University of Mexico (CFATA-UNAM), Boulevard Juriquilla 3001, Santiago de Querétaro, Querétaro 76230 (Mexico); Merino, Ulises [Dept. of Molecular Engineering of Materials, Center of Applied Physics and Advanced Technology, National Autonomous University of Mexico (CFATA-UNAM), Boulevard Juriquilla 3001, Santiago de Querétaro, Querétaro 76230 (Mexico); University of the Valley of Mexico (UVM), Boulevard Villas del Mesón 1000, Juriquilla, Santiago de Querétaro, Querétaro 76320 (Mexico); Vargas, Susana [Dept. of Molecular Engineering of Materials, Center of Applied Physics and Advanced Technology, National Autonomous University of Mexico (CFATA-UNAM), Boulevard Juriquilla 3001, Santiago de Querétaro, Querétaro 76230 (Mexico); Quintanilla, Francisco [University of the Valley of Mexico (UVM), Boulevard Villas del Mesón 1000, Juriquilla, Santiago de Querétaro, Querétaro 76320 (Mexico); Rodríguez, Rogelio, E-mail: rogelior@unam.mx [Dept. of Molecular Engineering of Materials, Center of Applied Physics and Advanced Technology, National Autonomous University of Mexico (CFATA-UNAM), Boulevard Juriquilla 3001, Santiago de Querétaro, Querétaro 76230 (Mexico)

    2016-04-01

    A biocompatible hybrid porous polymer–ceramic material was synthesized to be used as a biomarker in the treatment of breast cancer. This device was equipped with the capacity to release medicaments locally in a controlled manner. The biomaterial was Hydroxyapatite(HAp)-based and had a controlled pore size and pore volume fraction. It was implemented externally using a sharp end and a pair of barbed rings placed opposite each other to prevent relative movement once implanted. The biomarker was impregnated with cis-diamine dichloride platinum (II) [Cl{sub 2}-Pt-(NH{sub 3}){sub 2}]; the rate of release was obtained using inductively coupled plasma atomic emission spectroscopy (ICP-AES), and release occurred over the course of three months. Different release profiles were obtained as a function of the pore volume fraction. The biomaterial was characterized using scanning electron microscopy (SEM) and Raman spectroscopy. - Highlights: • A novel biocompatible hybrid porous polymer–ceramic material was synthesized. • The polymer–ceramic (HAp-based) material was used to prepare a biomarker. • The biomarker was impregnated with cis-diamine dichloride platinum (II). • The rate of cisplatin release was determined using inductively coupled plasma. • The kinetics of the cisplatin release was studied varying the biomarker porosity.

  20. Blood Based Biomarkers of Early Onset Breast Cancer

    Science.gov (United States)

    2016-12-01

    any penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN...blood donated to blood banks ~15 years ago and subsequently linked to the California Cancer Registry. In this fashion, we have access to blood from

  1. Mechanisms of CTC Biomarkers in Breast Cancer Brain Metastasis

    Science.gov (United States)

    2015-10-01

    bioinformatics.istge.it/ clima /) and from each other (Fig. 2b). Third, we interrogated CTC subsets by their abilities to be viable and expand in vitro. We...employing cancer cell lines from available databases (http://bioinfor- matics.istge.it/ clima /) and from each other (Fig. 2b). Third, we interrogated CTC

  2. Circadian disruption and biomarkers of tumor progression in breast cancer patients awaiting surgery.

    Science.gov (United States)

    Cash, E; Sephton, S E; Chagpar, A B; Spiegel, D; Rebholz, W N; Zimmaro, L A; Tillie, J M; Dhabhar, F S

    2015-08-01

    Psychological distress, which can begin with cancer diagnosis and continue with treatment, is linked with circadian and endocrine disruption. In turn, circadian/endocrine factors are potent modulators of cancer progression. We hypothesized that circadian rest-activity rhythm disruption, distress, and diurnal cortisol rhythms would be associated with biomarkers of tumor progression in the peripheral blood of women awaiting breast cancer surgery. Breast cancer patients (n=43) provided actigraphic data on rest-activity rhythm, cancer-specific distress (IES, POMS), saliva samples for assessment of diurnal cortisol rhythm, cortisol awakening response (CAR), and diurnal mean. Ten potential markers of tumor progression were quantified in serum samples and grouped by exploratory factor analysis. Analyses yielded three factors, which appear to include biomarkers reflecting different aspects of tumor progression. Elevated factor scores indicate both high levels and strong clustering among serum signals. Factor 1 included VEGF, MMP-9, and TGF-β; suggesting tumor invasion/immunosuppression. Factor 2 included IL-1β, TNF-α, IL-6R, MCP-1; suggesting inflammation/chemotaxis. Factor 3 included IL-6, IL-12, IFN-γ; suggesting inflammation/TH1-type immunity. Hierarchical regressions adjusting age, stage and socioeconomic status examined associations of circadian, distress, and endocrine variables with these three factor scores. Patients with poor circadian coordination as measured by rest-activity rhythms had higher Factor 1 scores (R(2)=.160, p=.038). Patients with elevated CAR also had higher Factor 1 scores (R(2)=.293, p=.020). These relationships appeared to be driven largely by VEGF concentrations. Distress was not related to tumor-relevant biomarkers, and no other significant relationships emerged. Women with strong circadian activity rhythms showed less evidence of tumor promotion and/or progression as indicated by peripheral blood biomarkers. The study was not equipped to

  3. Biomarker and Phenotypic Risk Factors for Breast Cancer Lymphedema | Division of Cancer Prevention

    Science.gov (United States)

    DESCRIPTION (provided by applicant): Lymphedema (LE) following treatment for breast cancer is the most common form of secondary LE in the industrialized world. It occurs in 20% to 87% of patients following treatment for breast cancer and results in significant disability. At the present time, the definitive phenotypic, genotypic and epigenotypic predictors that place patients at highest risk for the development of LE are not known. |

  4. Identification of the SUMO E3 ligase PIAS1 as a potential survival biomarker in breast cancer.

    Science.gov (United States)

    Chanda, Ayan; Chan, Angela; Deng, Lili; Kornaga, Elizabeth N; Enwere, Emeka K; Morris, Donald G; Bonni, Shirin

    2017-01-01

    Metastasis is the ultimate cause of breast cancer related mortality. Epithelial-mesenchymal transition (EMT) is thought to play a crucial role in the metastatic potential of breast cancer. Growing evidence has implicated the SUMO E3 ligase PIAS1 in the regulation of EMT in mammary epithelial cells and breast cancer metastasis. However, the relevance of PIAS1 in human cancer and mechanisms by which PIAS1 might regulate breast cancer metastasis remain to be elucidated. Using tissue-microarray analysis (TMA), we report that the protein abundance and subcellular localization of PIAS1 correlate with disease specific overall survival of a cohort of breast cancer patients. In mechanistic studies, we find that PIAS1 acts via sumoylation of the transcriptional regulator SnoN to suppress invasive growth of MDA-MB-231 human breast cancer cell-derived organoids. Our studies thus identify the SUMO E3 ligase PIAS1 as a prognostic biomarker in breast cancer, and suggest a potential role for the PIAS1-SnoN sumoylation pathway in controlling breast cancer metastasis.

  5. A window-of-opportunity biomarker study of etodolac in resectable breast cancer

    Science.gov (United States)

    Schwab, Richard B; Kato, Shumei; Crain, Brian; Pu, Minya; Messer, Karen; Weidner, Noel; Blair, Sarah L; Wallace, Anne M; Carson, Dennis A; Parker, Barbara A

    2015-01-01

    Observational data show that nonsteroidal anti-inflammatory drug (NSAID) use is associated with a lower rate of breast cancer. We evaluated the effect of etodolac, an FDA-approved NSAID reported to inhibit cyclooxygenase (COX) enzymes and the retinoid X receptor alpha (RXR), on rationally identified potential biomarkers in breast cancer. Patients with resectable breast cancer planned for initial management with surgical resection were enrolled and took 400 mg of etodolac twice daily prior to surgery. Protein and gene expression levels for genes related to COX-2 and RXRα were evaluated in tumor samples from before and after etodolac exposure. Thirty subjects received etodolac and 17 subjects were assayed as contemporaneous or opportunistic controls. After etodolac exposure mean cyclin D1 protein levels, assayed by immunohistochemistry, decreased (P = 0.03). Notably, pre- versus post cyclin D1 gene expression change went from positive to negative with greater duration of etodolac exposure (r = −0.64, P = 0.01). Additionally, etodolac exposure was associated with a significant increase in COX-2 gene expression levels (fold change: 3.25 [95% CI: 1.9, 5.55]) and a trend toward increased β-catenin expression (fold change: 2.03 [95% CI: 0.93, 4.47]). In resectable breast cancer relatively brief exposure to the NSAID etodolac was associated with reduced cyclin D1 protein levels. Effect was also observed on cyclin D1 gene expression with decreasing levels with longer durations of drug exposure. Increased COX-2 gene expression was seen, possibly due to compensatory feedback. These data highlight the utility of even small clinical trials with access to biospecimens for pharmacodynamic studies. PMID:26275572

  6. Targeted radiosensitization with PARP1 inhibition: optimization of therapy and identification of biomarkers of response in breast cancer.

    Science.gov (United States)

    Feng, Felix Y; Speers, Corey; Liu, Meilan; Jackson, William C; Moon, Dominic; Rinkinen, Jacob; Wilder-Romans, Kari; Jagsi, Reshma; Pierce, Lori J

    2014-08-01

    Sustained locoregional control of breast cancer is a significant issue for certain patients. Inhibition of PARP1 is a promising strategy for radiosensitization (RS). We sought to optimize therapy with PARP1 inhibition and radiation (RT) by establishing the most effective treatment schedule, degree of PARP1-mediated RS, and identify early biomarkers predictive of efficacy in breast cancer models. Using clonogenic survival assays, we assessed intrinsic radiosensitivity and RS induced by PARP1 inhibition in breast cancer cell lines. Potential biomarkers of response were evaluated using western blotting, flow cytometry, and immunofluorescence with validation in vivo using tumor xenograft experiments. Across a panel of BC and normal breast epithelial cell lines, the PARP1 inhibitor ABT-888 preferentially radiosensitizes breast cancer (vs. normal) cells with enhancement ratios (EnhR) up to 2.3 independent of intrinsic BC subtype or BRCA mutational status. Concurrent and adjuvant therapy resulted in the highest EnhR of all schedules tested. The degree of RS did not correlate with pretreatment markers of PARP1 activity, DNA damage/repair, or cell cycle distribution. Increases in PARP1 activity 24 h after RT were associated with sensitivity after combination treatment. Findings were confirmed in breast cancer xenograft models. Our study demonstrates that PARP1 inhibition improves the therapeutic index of RT independent of BC subtype or BRCA1 mutational status and that PARP1 activity may serve as a clinically relevant biomarker of response. These studies have led to a clinical trial (TBCRC024) incorporating intratreatment biomarker analyses of PARP1 inhibitors and RT in breast cancer patients.

  7. Novel Functions of EZH2 in Triple Negative Breast Cancer: Translation in to New Biomarker and Treatment Strategies

    Science.gov (United States)

    2016-07-01

    Translation into New Biomarker and Treatment Strategies 5b. GRANT NUMBER Bc140965 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Celina G. Kleer, M.D...1 AWARD NUMBER: W81XWH-15-1-0019 TITLE: Novel Functions of EZH2 in Triple Negative Breast Cancer: Translation in to New Biomarker and...Treatment Strategies . PRINCIPAL INVESTIGATOR: Celina G. Kleer, M.D. CONTRACTING ORGANIZATION: University of Michigan Ann Arbor, MI 48109 REPORT DATE

  8. Etiology and early detection of breast cancer : Biomarkers, lifestyle and mammographic density

    NARCIS (Netherlands)

    Emaus, M.J.

    2015-01-01

    In the Netherlands, one in seven women will develop breast cancer at some point during her lifetime. Although breast cancer mortality has declined, still 23% of the breast cancer patients dies from the disease within 10 years after initial diagnosis. This emphasizes the importance of research on

  9. Chromosome 1q21.3 amplification is a trackable biomarker and actionable target for breast cancer recurrence.

    Science.gov (United States)

    Goh, Jian Yuan; Feng, Min; Wang, Wenyu; Oguz, Gokce; Yatim, Siti Maryam J M; Lee, Puay Leng; Bao, Yi; Lim, Tse Hui; Wang, Panpan; Tam, Wai Leong; Kodahl, Annette R; Lyng, Maria B; Sarma, Suman; Lin, Selena Y; Lezhava, Alexander; Yap, Yoon Sim; Lim, Alvin S T; Hoon, Dave S B; Ditzel, Henrik J; Lee, Soo Chin; Tan, Ern Yu; Yu, Qiang

    2017-11-01

    Tumor recurrence remains the main reason for breast cancer-associated mortality, and there are unmet clinical demands for the discovery of new biomarkers and development of treatment solutions to benefit patients with breast cancer at high risk of recurrence. Here we report the identification of chromosomal copy-number amplification at 1q21.3 that is enriched in subpopulations of breast cancer cells bearing characteristics of tumor-initiating cells (TICs) and that strongly associates with breast cancer recurrence. Amplification is present in ∼10-30% of primary tumors but in more than 70% of recurrent tumors, regardless of breast cancer subtype. Detection of amplification in cell-free DNA (cfDNA) from blood is strongly associated with early relapse in patients with breast cancer and could also be used to track the emergence of tumor resistance to chemotherapy. We further show that 1q21.3-encoded S100 calcium-binding protein (S100A) family members, mainly S100A7, S100A8, and S100A9 (S100A7/8/9), and IL-1 receptor-associated kinase 1 (IRAK1) establish a reciprocal feedback loop driving tumorsphere growth. Notably, this functional circuitry can be disrupted by the small-molecule kinase inhibitor pacritinib, leading to preferential impairment of the growth of 1q21.3-amplified breast tumors. Our study uncovers the 1q21.3-directed S100A7/8/9-IRAK1 feedback loop as a crucial component of breast cancer recurrence, serving as both a trackable biomarker and an actionable therapeutic target for breast cancer.

  10. Biomarker and pharmacologic evaluation of the γ-secretase inhibitor PF-03084014 in breast cancer models.

    Science.gov (United States)

    Zhang, Cathy C; Pavlicek, Adam; Zhang, Qin; Lira, Maruja E; Painter, Cory L; Yan, Zhengming; Zheng, Xianxian; Lee, Nathan V; Ozeck, Mark; Qiu, Ming; Zong, Qing; Lappin, Patrick B; Wong, Anthony; Rejto, Paul A; Smeal, Tod; Christensen, James G

    2012-09-15

    We aimed to assess the biologic activity of PF-03084014 in breast xenograft models. The biomarkers for mechanism and patient stratification were also explored. The in vitro and in vivo properties of PF-03084014 were investigated. The mRNA expressions of 40 key Notch pathway genes at baseline or after treatment were analyzed to link with the antitumor efficacy of PF-03084014 in a panel of breast cancer xenograft models. In vitro, PF-03084014 exhibited activity against tumor cell migration, endothelial cell tube formation, and mammosphere formation. In vivo, we observed apoptosis, antiproliferation, reduced tumor cell self-renewal ability, impaired tumor vasculature, and decreased metastasis activity after the treatment of PF-03084014. PF-03084014 treatment displayed significant antitumor activity in 10 of the 18 breast xenograft models. However, the antitumor efficacy in most models did not correlate with the in vitro antiproliferation results in the corresponding cell lines, suggesting the critical involvement of tumor microenvironment during Notch activation. In the tested breast xenograft models, the baseline expressions of the Notch receptors, ligands, and the cleaved Notch1 failed to predict the antitumor response to PF-03084014, whereas several Notch pathway target genes, including HEY2, HES4, and HES3, strongly corresponded with the response with a P value less than 0.01. Many of the best molecular predictors of response were also significantly modulated following PF-03084014 treatment. PF-03084014 showed antitumor and antimetastatic properties via pleiotropic mechanisms. The Notch pathway downstream genes may be used to predict the antitumor activity of PF-03084014 and enrich for responders among breast cancer patients. ©2012 AACR.

  11. MicroRNA expression as risk biomarker of breast cancer metastasis: a pilot retrospective case-cohort study.

    Science.gov (United States)

    Marino, Augusto L F; Evangelista, Adriane F; Vieira, René A C; Macedo, Taciane; Kerr, Ligia M; Abrahão-Machado, Lucas Faria; Longatto-Filho, Adhemar; Silveira, Henrique C S; Marques, Marcia M C

    2014-10-02

    MicroRNAs (miRNAs) are small, non-coding RNA molecules involved in post-transcriptional gene regulation and have recently been shown to play a role in cancer metastasis. In solid tumors, especially breast cancer, alterations in miRNA expression contribute to cancer pathogenesis, including metastasis. Considering the emerging role of miRNAs in metastasis, the identification of predictive markers is necessary to further the understanding of stage-specific breast cancer development. This is a retrospective analysis that aimed to identify molecular biomarkers related to distant breast cancer metastasis development. A retrospective case cohort study was performed in 64 breast cancer patients treated during the period from 1998-2001. The case group (n = 29) consisted of patients with a poor prognosis who presented with breast cancer recurrence or metastasis during follow up. The control group (n = 35) consisted of patients with a good prognosis who did not develop breast cancer recurrence or metastasis. These patient groups were stratified according to TNM clinical stage (CS) I, II and III, and the main clinical features of the patients were homogeneous. MicroRNA profiling was performed and biomarkers related to metastatic were identified independent of clinical stage. Finally, a hazard risk analysis of these biomarkers was performed to evaluate their relation to metastatic potential. MiRNA expression profiling identified several miRNAs that were both specific and shared across all clinical stages (p ≤ 0.05). Among these, we identified miRNAs previously associated with cell motility (let-7 family) and distant metastasis (hsa-miR-21). In addition, hsa-miR-494 and hsa-miR-21 were deregulated in metastatic cases of CSI and CSII. Furthermore, metastatic miRNAs shared across all clinical stages did not present high sensitivity and specificity when compared to specific-CS miRNAs. Between them, hsa-miR-183 was the most significative of CSII, which miRNAs combination for CSII

  12. Identification of microRNA biomarkers in the blood of breast cancer patients based on microRNA profiling.

    Science.gov (United States)

    Zhang, Kai; Wang, Ya-Wen; Wang, Yan-Yan; Song, Yu; Zhu, Jiang; Si, Peng-Chao; Ma, Rong

    2017-07-01

    Accumulating evidence indicates that human circulating microRNAs (miRNAs) could serve as diagnostic and prognostic biomarkers in various cancers. We aimed to explore novel miRNA biomarkers in the blood of breast cancer patients based on miRNA profiling. A miRCURY™ LNA Array was used to identify differentially altered miRNAs in the whole blood of breast cancer patients (n=6) and healthy controls (n=6). Levels of candidate miRNAs were quantified by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) in whole blood specimens of 15 breast cancer patients and 13 age-matched healthy control individuals. The miRWalk database was used to predict miRNA targets and the DAVID tool was used to identify significant enrichment pathways. A total of 171 differentially expressed miRNAs were identified by microarray, including 169 upregulated and 2 downregulated miRNAs in breast cancer. Five upregulated miRNAs (miR-30b-5p, miR-96-5p, miR-182-5p, miR-374b-5p, and miR-942-5p) were confirmed by qRT-PCR. The areas under the receiver operating characteristic curve of miR-30b-5p, miR-96-5p, miR-182-5p, miR-374b-5p, and miR-942-5p were 0.9333, 0.7692, 0.7590, 0.8256, and 0.8128, respectively. Importantly, upregulation of these five miRNAs was observed even in patients with very early-stage breast cancer. A total of 855 genes were predicted to be targeted by the five miRNAs, and the one cut domain family member 2 gene (ONECUT2) was a shared target of the five miRNAs. Analysis of publicly available data revealed that these dysregulated miRNAs and the target genes were associated with the survival of breast cancer patients. Furthermore, the five miRNAs were significantly enriched in numerous cancer-related pathways, including "MicroRNAs in cancer", "Pathways in cancer", "FoxO signaling pathway", "Ras signaling pathway", "Rap1 signaling pathway", "MAPK signaling pathway", and "PI3K-Akt signaling pathway". Our data support the potential of the five identified miRNAs as

  13. Optimized high-throughput microRNA expression profiling provides novel biomarker assessment of clinical prostate and breast cancer biopsies

    Directory of Open Access Journals (Sweden)

    Fedele Vita

    2006-06-01

    Full Text Available Abstract Background Recent studies indicate that microRNAs (miRNAs are mechanistically involved in the development of various human malignancies, suggesting that they represent a promising new class of cancer biomarkers. However, previously reported methods for measuring miRNA expression consume large amounts of tissue, prohibiting high-throughput miRNA profiling from typically small clinical samples such as excision or core needle biopsies of breast or prostate cancer. Here we describe a novel combination of linear amplification and labeling of miRNA for highly sensitive expression microarray profiling requiring only picogram quantities of purified microRNA. Results Comparison of microarray and qRT-PCR measured miRNA levels from two different prostate cancer cell lines showed concordance between the two platforms (Pearson correlation R2 = 0.81; and extension of the amplification, labeling and microarray platform was successfully demonstrated using clinical core and excision biopsy samples from breast and prostate cancer patients. Unsupervised clustering analysis of the prostate biopsy microarrays separated advanced and metastatic prostate cancers from pooled normal prostatic samples and from a non-malignant precursor lesion. Unsupervised clustering of the breast cancer microarrays significantly distinguished ErbB2-positive/ER-negative, ErbB2-positive/ER-positive, and ErbB2-negative/ER-positive breast cancer phenotypes (Fisher exact test, p = 0.03; as well, supervised analysis of these microarray profiles identified distinct miRNA subsets distinguishing ErbB2-positive from ErbB2-negative and ER-positive from ER-negative breast cancers, independent of other clinically important parameters (patient age; tumor size, node status and proliferation index. Conclusion In sum, these findings demonstrate that optimized high-throughput microRNA expression profiling offers novel biomarker identification from typically small clinical samples such as breast

  14. Long-term Diet and Biomarker Changes after a Short-term Intervention among Hispanic Breast Cancer Survivors: The ¡Cocinar Para Su Salud! Randomized Controlled Trial.

    Science.gov (United States)

    Greenlee, Heather; Ogden Gaffney, Ann; Aycinena, A Corina; Koch, Pam; Contento, Isobel; Karmally, Wahida; Richardson, John M; Shi, Zaixing; Lim, Emerson; Tsai, Wei-Yann; Santella, Regina M; Blaner, William S; Clugston, Robin D; Cremers, Serge; Pollak, Susan; Sirosh, Iryna; Crew, Katherine D; Maurer, Matthew; Kalinsky, Kevin; Hershman, Dawn L

    2016-11-01

    Among Hispanic breast cancer survivors, we examined the long-term effects of a short-term culturally based dietary intervention on increasing fruits/vegetables (F/V), decreasing fat, and changing biomarkers associated with breast cancer recurrence risk. Spanish-speaking women (n = 70) with a history of stage 0-III breast cancer who completed treatment were randomized to ¡Cocinar Para Su Salud! (n = 34), a culturally based 9-session program (24 hours over 12 weeks, including nutrition education, cooking classes, and food-shopping field trips), or a control group (n = 36, written dietary recommendations for breast cancer survivors). Diet recalls, fasting blood, and anthropometric measures were collected at baseline, 6, and 12 months. We report changes between groups at 12 months in dietary intake and biomarkers using 2-sample Wilcoxon t tests and generalized estimating equation (GEE) models. At 12 months, the intervention group compared with the control group reported higher increases in mean daily F/V servings (total: +2.0 vs. -0.4; P Salud! program was effective at increasing long-term F/V intake in Hispanic breast cancer survivors and changed biomarkers associated with breast cancer recurrence risk. It is possible for short-term behavioral interventions to have long-term effects on behaviors and biomarkers in minority cancer patient populations. Results can inform future study designs. Cancer Epidemiol Biomarkers Prev; 25(11); 1491-502. ©2016 AACR. ©2016 American Association for Cancer Research.

  15. Trace elements as tumor biomarkers and prognostic factors in breast cancer: a study through energy dispersive x-ray fluorescence

    Science.gov (United States)

    2012-01-01

    Background The application and better understanding of traditional and new breast tumor biomarkers and prognostic factors are increasing due to the fact that they are able to identify individuals at high risk of breast cancer, who may benefit from preventive interventions. Also, biomarkers can make possible for physicians to design an individualized treatment for each patient. Previous studies showed that trace elements (TEs) determined by X-Ray Fluorescence (XRF) techniques are found in significantly higher concentrations in neoplastic breast tissues (malignant and benign) when compared with normal tissues. The aim of this work was to evaluate the potential of TEs, determined by the use of the Energy Dispersive X-Ray Fluorescence (EDXRF) technique, as biomarkers and prognostic factors in breast cancer. Methods By using EDXRF, we determined Ca, Fe, Cu, and Zn trace elements concentrations in 106 samples of normal and breast cancer tissues. Cut-off values for each TE were determined through Receiver Operating Characteristic (ROC) analysis from the TEs distributions. These values were used to set the positive or negative expression. This expression was subsequently correlated with clinical prognostic factors through Fisher’s exact test and chi-square test. Kaplan Meier survival curves were also evaluated to assess the effect of the expression of TEs in the overall patient survival. Results Concentrations of TEs are higher in neoplastic tissues (malignant and benign) when compared with normal tissues. Results from ROC analysis showed that TEs can be considered a tumor biomarker because, after establishing a cut-off value, it was possible to classify different tissues as normal or neoplastic, as well as different types of cancer. The expression of TEs was found statistically correlated with age and menstrual status. The survival curves estimated by the Kaplan-Meier method showed that patients with positive expression for Cu presented a poor overall survival (p

  16. Applicability of HIN-1, MGMT and RASSF1A promoter methylation as biomarkers for detecting field cancerization in breast cancer.

    Science.gov (United States)

    Spitzwieser, Melanie; Holzweber, Elisabeth; Pfeiler, Georg; Hacker, Stefan; Cichna-Markl, Margit

    2015-09-14

    It has been shown in some articles that genetic and epigenetic abnormalities cannot only be found in tumor tissues but also in adjacent regions that appear histologically normal. This phenomenon is metaphorically called field cancerization or field defect. Field cancerization is regarded as clinically significant because it is assumed to be an important factor in local recurrence of cancer. As the field showing these molecular abnormalities may not be removed completely by surgery, these changes might lead to neoplasms and subsequent transformation to a tumor. We aimed to investigate the applicability of the methylation status of six tumor suppressor genes as biomarkers for detecting field cancerization in breast cancer. The promoter methylation status of CCND2, DAPK1, GSTP1, HIN-1, MGMT and RASSF1A was determined by methylation-sensitive high-resolution melting (MS-HRM) analysis. MS-HRM methods for CCND2, MGMT and RASSF1A were developed in-house, primer sequences for DAPK1, GSTP1 and HIN-1 have already been published. Biopsy samples were taken from tumor, tumor-adjacent and tumor-distant tissue from 17 breast cancer patients. Normal breast tissues of four healthy women served as controls. All MS-HRM methods proved to be very sensitive. LODs were in the range from 0.1 to 1.5 %, LOQs ranged from 0.3 to 5.3 %. A total of 94 %, 82 % and 65 % of the tumors showed methylation of RASSF1A, HIN-1 and MGMT promoters, respectively. The methylation status of these promoters was significantly lower in tumor-distant tissues than in tumor tissues. Tumor-adjacent tissues showed higher methylation status of RASSF1A, HIN-1 and MGMT promoters than tumor-distant tissues, indicating field cancerization. The methylation status of the HIN-1 promoter in tumor-adjacent tissues was found to correlate strongly with that in the corresponding tumors (r = 0.785, p cancerization. Further investigation is needed to test whether it can be used for defining surgical margins in order to

  17. Enhanced resting-state dynamics of the hemoglobin signal as a novel biomarker for detection of breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Graber, Harry L., E-mail: harry.graber@downstate.edu; Xu, Yong; Barbour, Randall L. [SUNY Downstate Medical Center, Brooklyn, New York 11203 (United States); NIRx Medical Technologies, LLC, Glen Head, New York 11545 (United States); Al abdi, Rabah [Department of Biomedical Engineering, Jordan University of Science and Technology, Irbid 22110 (Jordan); Asarian, Armand P.; Pappas, Peter J. [The Brooklyn Hospital Center, Brooklyn, New York 11201 (United States); Dresner, Lisa [SUNY Downstate Medical Center, Brooklyn, New York 11203 (United States); Patel, Naresh [Kaiser Permanente-Modesto Medical Center, Modesto, California 95356 (United States); Jagarlamundi, Kuppuswamy [Sarah Bush Lincoln Regional Cancer Center, 1000 Health Center Drive, Mattoon, Illinois 61938 (United States); Solomon, William B. [Maimonides Medical Center, Brooklyn, New York 11219 (United States)

    2015-11-15

    Purpose: The work presented here demonstrates an application of diffuse optical tomography (DOT) to the problem of breast-cancer diagnosis. The potential for using spatial and temporal variability measures of the hemoglobin signal to identify useful biomarkers was studied. Methods: DOT imaging data were collected using two instrumentation platforms the authors developed, which were suitable for exploring tissue dynamics while performing a simultaneous bilateral exam. For each component of the hemoglobin signal (e.g., total, oxygenated), the image time series was reduced to eight scalar metrics that were affected by one or more dynamic properties of the breast microvasculature (e.g., average amplitude, amplitude heterogeneity, strength of spatial coordination). Receiver-operator characteristic (ROC) analyses, comparing groups of subjects with breast cancer to various control groups (i.e., all noncancer subjects, only those with diagnosed benign breast pathology, and only those with no known breast pathology), were performed to evaluate the effect of cancer on the magnitudes of the metrics and of their interbreast differences and ratios. Results: For women with known breast cancer, simultaneous bilateral DOT breast measures reveal a marked increase in the resting-state amplitude of the vasomotor response in the hemoglobin signal for the affected breast, compared to the contralateral, noncancer breast. Reconstructed 3D spatial maps of observed dynamics also show that this behavior extends well beyond the tumor border. In an effort to identify biomarkers that have the potential to support clinical aims, a group of scalar quantities extracted from the time series measures was systematically examined. This analysis showed that many of the quantities obtained by computing paired responses from the bilateral scans (e.g., interbreast differences, ratios) reveal statistically significant differences between the cancer-positive and -negative subject groups, while the

  18. Validation of the 18-gene classifier as a prognostic biomarker of distant metastasis in breast cancer.

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    Skye Hung-Chun Cheng

    Full Text Available We validated an 18-gene classifier (GC initially developed to predict local/regional recurrence after mastectomy in estimating distant metastasis risk. The 18-gene scoring algorithm defines scores as: <21, low risk; ≥21, high risk. Six hundred eighty-three patients with primary operable breast cancer and fresh frozen tumor tissues available were included. The primary outcome was the 5-year probability of freedom from distant metastasis (DMFP. Two external datasets were used to test the predictive accuracy of 18-GC. The 5-year rates of DMFP for patients classified as low-risk (n = 146, 21.7% and high-risk (n = 537, 78.6% were 96.2% (95% CI, 91.1%-98.8% and 80.9% (74.6%-81.9%, respectively (median follow-up interval, 71.8 months. The 5-year rates of DMFP of the low-risk group in stage I (n = 62, 35.6%, stage II (n = 66, 20.1%, and stage III (n = 18, 10.3% were 100%, 94.2% (78.5%-98.5%, and 90.9% (50.8%-98.7%, respectively. Multivariate analysis revealed that 18-GC is an independent prognostic factor of distant metastasis (adjusted hazard ratio, 5.1; 95% CI, 1.8-14.1; p = 0.0017 for scores of ≥21. External validation showed that the 5-year rate of DMFP in the low- and high-risk patients was 94.1% (82.9%-100% and 80.3% (70.7%-89.9%, p = 0.06 in a Singapore dataset, and 89.5% (81.9%-94.1% and 73.6% (67.2%-79.0%, p = 0.0039 in the GEO-GSE20685 dataset, respectively. In conclusion, 18-GC is a viable prognostic biomarker for breast cancer to estimate distant metastasis risk.

  19. Biomarkers of folate and vitamin B12 and breast cancer risk: report from the EPIC cohort.

    Science.gov (United States)

    Matejcic, M; de Batlle, J; Ricci, C; Biessy, C; Perrier, F; Huybrechts, I; Weiderpass, E; Boutron-Ruault, M C; Cadeau, C; His, M; Cox, D G; Boeing, H; Fortner, R T; Kaaks, R; Lagiou, P; Trichopoulou, A; Benetou, V; Tumino, R; Panico, S; Sieri, S; Palli, D; Ricceri, F; Bueno-de-Mesquita, H B As; Skeie, G; Amiano, P; Sánchez, M J; Chirlaque, M D; Barricarte, A; Quirós, J R; Buckland, G; van Gils, C H; Peeters, P H; Key, T J; Riboli, E; Gylling, B; Zeleniuch-Jacquotte, A; Gunter, M J; Romieu, I; Chajès, V

    2017-03-15

    Epidemiological studies have reported inconsistent findings for the association between B vitamins and breast cancer (BC) risk. We investigated the relationship between biomarkers of folate and vitamin B12 and the risk of BC in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Plasma concentrations of folate and vitamin B12 were determined in 2,491 BC cases individually matched to 2,521 controls among women who provided baseline blood samples. Multivariable logistic regression models were used to estimate odds ratios by quartiles of either plasma B vitamin. Subgroup analyses by menopausal status, hormone receptor status of breast tumors (estrogen receptor [ER], progesterone receptor [PR] and human epidermal growth factor receptor 2 [HER2]), alcohol intake and MTHFR polymorphisms (677C > T and 1298A > C) were also performed. Plasma levels of folate and vitamin B12 were not significantly associated with the overall risk of BC or by hormone receptor status. A marginally positive association was found between vitamin B12 status and BC risk in women consuming above the median level of alcohol (ORQ4-Q1  = 1.26; 95% CI 1.00-1.58; Ptrend  = 0.05). Vitamin B12 status was also positively associated with BC risk in women with plasma folate levels below the median value (ORQ4-Q1  = 1.29; 95% CI 1.02-1.62; Ptrend  = 0.03). Overall, folate and vitamin B12 status was not clearly associated with BC risk in this prospective cohort study. However, potential interactions between vitamin B12 and alcohol or folate on the risk of BC deserve further investigation. © 2016 UICC.

  20. Validation of the 18-gene classifier as a prognostic biomarker of distant metastasis in breast cancer.

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    Cheng, Skye Hung-Chun; Huang, Tzu-Ting; Cheng, Yu-Hao; Tan, Tee Benita Kiat; Horng, Chen-Fang; Wang, Yong Alison; Brian, Nicholas Shannon; Shih, Li-Sun; Yu, Ben-Long

    2017-01-01

    We validated an 18-gene classifier (GC) initially developed to predict local/regional recurrence after mastectomy in estimating distant metastasis risk. The 18-gene scoring algorithm defines scores as: breast cancer and fresh frozen tumor tissues available were included. The primary outcome was the 5-year probability of freedom from distant metastasis (DMFP). Two external datasets were used to test the predictive accuracy of 18-GC. The 5-year rates of DMFP for patients classified as low-risk (n = 146, 21.7%) and high-risk (n = 537, 78.6%) were 96.2% (95% CI, 91.1%-98.8%) and 80.9% (74.6%-81.9%), respectively (median follow-up interval, 71.8 months). The 5-year rates of DMFP of the low-risk group in stage I (n = 62, 35.6%), stage II (n = 66, 20.1%), and stage III (n = 18, 10.3%) were 100%, 94.2% (78.5%-98.5%), and 90.9% (50.8%-98.7%), respectively. Multivariate analysis revealed that 18-GC is an independent prognostic factor of distant metastasis (adjusted hazard ratio, 5.1; 95% CI, 1.8-14.1; p = 0.0017) for scores of ≥21. External validation showed that the 5-year rate of DMFP in the low- and high-risk patients was 94.1% (82.9%-100%) and 80.3% (70.7%-89.9%, p = 0.06) in a Singapore dataset, and 89.5% (81.9%-94.1%) and 73.6% (67.2%-79.0%, p = 0.0039) in the GEO-GSE20685 dataset, respectively. In conclusion, 18-GC is a viable prognostic biomarker for breast cancer to estimate distant metastasis risk.

  1. Long non-coding RNAs may serve as biomarkers in breast cancer combined with primary lung cancer

    Science.gov (United States)

    Mao, Weimin; Chen, Bo; Yang, Shifeng; Ding, Xiaowen; Zou, Dehong; Mo, Wenju; He, Xiangming; Zhang, Xiping

    2017-01-01

    Long non-coding RNAs (lncRNAs) have been shown to play important regulatory role in certain type of cancers biology, including breast and lung cancers. However, the lncRNA expression in breast cancer combined with primary lung cancer remains unknown. In this study, databases of the Cancer Genome Atlas (TCGA) and the lncRNA profiler of contained candidate 192 lncRNAs were utilized. 11 lncRNAs were differentially expressed in breast cancer, 9 candidate lncRNAs were differentially expressed in lung cancer. In order to find the aberrant expression of lncRNAs in breast cancer combined with primary lung cancer, seven samples of primary breast cancer and lung cancer were studied for the expression of selected lncRNAs. The results showed that SNHG6 and NEAT1 were reversely expressed in breast cancer combined with primary lung cancer compared with primary breast or lung cancer. In addition, a significant correlation of lncRNAs was found in the patients whose age was above 56 in breast cancer. What's more, PVT1 expression was negatively correlated with the pathological stage, and the level of ER, PR, HER2, p53 in breast cancer. Furthermore, lncRNA expression did not have significant relationship with the 5-year survival of patients with breast cancer combined with primary lung cancer. The findings revealed that PVT1, SNHG6, NEAT1 may serve as a prognostic marker for breast cancer combined with primary lung cancer. Therefore, these lncRNAs are potential molecular indicators in the diagnosis and prognosis of cancer in the future. PMID:28938549

  2. HP1β is a biomarker for breast cancer prognosis and PARP inhibitor therapy.

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    Young-Ho Lee

    Full Text Available Members of the heterochromatin protein 1 family (HP1α, β and γ are mostly associated with heterochromatin and play important roles in gene regulation and DNA damage response. Altered expression of individual HP1 subtype has profound impacts on cell proliferation and tumorigenesis. We analyzed the expression profile of HP1 family by data mining using a published microarray data set coupled with retrospective immunohistochemistry analyses of archived breast cancer biospecimens. We found that the patient group overexpressing HP1β mRNA is associated with poorly differentiated breast tumors and with a significantly lower survival rate. Immunohistochemical staining against HP1α, HP1β and HP1γ shows that respective HP1 expression level is frequently altered in breast cancers. 57.4-60.1% of samples examined showed high HP1β expression and 39.9-42.6 % of examined tumors showed no or low expression of each HP1 subtype. Interestingly, comparative analysis on HP1 expression profile and breast cancer markers revealed a positive correlation between the respective expression level of all three HP1 subtypes and Ki-67, a cell proliferation and well-known breast cancer marker. To explore the effect of individual HP1 on PARP inhibitor therapy for breast cancer, MCF7 breast cancer cells and individually HP1-depleted MCF7 cells were treated with PARP inhibitor ABT-888 with or without carboplatin. Notably, HP1β-knockdown cells are hypersensitive to the PARP inhibitor ABT-888 alone and its combination with carboplatin. In summary, while increased HP1β expression is associated with the poor prognosis in breast cancer, compromised HP1β abundance may serve as a useful predictive marker for chemotherapy, including PARP inhibitors against breast cancer.

  3. Novel methylated biomarkers and a robust assay to detect circulating tumor DNA in metastatic breast cancer.

    Science.gov (United States)

    Fackler, Mary Jo; Lopez Bujanda, Zoila; Umbricht, Christopher; Teo, Wei Wen; Cho, Soonweng; Zhang, Zhe; Visvanathan, Kala; Jeter, Stacie; Argani, Pedram; Wang, Chenguang; Lyman, Jaclyn P; de Brot, Marina; Ingle, James N; Boughey, Judy; McGuire, Kandace; King, Tari A; Carey, Lisa A; Cope, Leslie; Wolff, Antonio C; Sukumar, Saraswati

    2014-04-15

    The ability to consistently detect cell-free tumor-specific DNA in peripheral blood of patients with metastatic breast cancer provides the opportunity to detect changes in tumor burden and to monitor response to treatment. We developed cMethDNA, a quantitative multiplexed methylation-specific PCR assay for a panel of ten genes, consisting of novel and known breast cancer hypermethylated markers identified by mining our previously reported study of DNA methylation patterns in breast tissue (103 cancer, 21 normal on the Illumina HumanMethylation27 Beadchip) and then validating the 10-gene panel in The Cancer Genome Atlas project breast cancer methylome database. For cMethDNA, a fixed physiologic level (50 copies) of artificially constructed, standard nonhuman reference DNA specific for each gene is introduced in a constant volume of serum (300 μL) before purification of the DNA, facilitating a sensitive, specific, robust, and quantitative assay of tumor DNA, with broad dynamic range. Cancer-specific methylated DNA was detected in training (28 normal, 24 cancer) and test (27 normal, 33 cancer) sets of recurrent stage IV patient sera with a sensitivity of 91% and a specificity of 96% in the test set. In a pilot study, cMethDNA assay faithfully reflected patient response to chemotherapy (N = 29). A core methylation signature present in the primary breast cancer was retained in serum and metastatic tissues collected at autopsy two to 11 years after diagnosis of the disease. Together, our data suggest that the cMethDNA assay can detect advanced breast cancer, and monitor tumor burden and treatment response in women with metastatic breast cancer. ©2014 AACR.

  4. Characterisation of male breast cancer: a descriptive biomarker study from a large patient series.

    Science.gov (United States)

    Humphries, Matthew P; Sundara Rajan, Sreekumar; Honarpisheh, Hedieh; Cserni, Gabor; Dent, Jo; Fulford, Laura; Jordan, Lee B; Jones, J Louise; Kanthan, Rani; Litwiniuk, Maria; Di Benedetto, Anna; Mottolese, Marcella; Provenzano, Elena; Shousha, Sami; Stephens, Mark; Kulka, Janina; Ellis, Ian O; Titloye, Akinwale N; Hanby, Andrew M; Shaaban, Abeer M; Speirs, Valerie

    2017-03-28

    Male breast cancer (MBC) is rare. We assembled 446 MBCs on tissue microarrays and assessed clinicopathological information, together with data from 15 published studies, totalling 1984 cases. By immunohistochemistry we investigated 14 biomarkers (ERα, ERβ1, ERβ2, ERβ5, PR, AR, Bcl-2, HER2, p53, E-cadherin, Ki67, survivin, prolactin, FOXA1) for survival impact. The main histological subtype in our cohort and combined analyses was ductal (81%, 83%), grade 2; (40%, 44%), respectively. Cases were predominantly ERα (84%, 82%) and PR positive (74%, 71%), respectively, with HER2 expression being infrequent (2%, 10%), respectively. In our cohort, advanced age (>67) was the strongest predictor of overall (OS) and disease free survival (DFS) (p = 0.00001; p = 0.01, respectively). Node positivity negatively impacted DFS (p = 0.04). FOXA1 p = 0.005) and AR p = 0.009) were both positively prognostic for DFS, remaining upon multivariate analysis. Network analysis showed ERα, AR and FOXA1 significantly correlated. In summary, the principle phenotype of MBC was luminal A, ductal, grade 2. In ERα+ MBC, only AR had prognostic significance, suggesting AR blockade could be employed therapeutically.

  5. An optofluidic metasurface for lateral flow-through detection of breast cancer biomarker.

    Science.gov (United States)

    Wang, Yifei; Ali, Md Azahar; Chow, Edmond K C; Dong, Liang; Lu, Meng

    2018-02-17

    The rapid growth of point-of-care tests demands for biosensors with high sensitivity and small size. This paper demonstrates an optofluidic metasurface that combines silicon-on-insulator (SOI) nanophotonics and nanofluidics to realize a high-performance, lateral flow-through biosensor. The metasurface is made of a periodic array of silicon nanoposts on an SOI substrate, and functionalized with specific receptor molecules. Bonding of a polydimethylsiloxane slab directly onto the surface results in an ultracompact biosensor, where analyte solutions are restricted to flow only in the space between the nanoposts. No flow exists above the nanoposts. This sensor design overcomes the issue with diffusion-limited detection of many other biosensors. The lateral flow-through feature, in conjunction with high-Q resonance modes associated with optical bound states of the metasurface, offers an improved sensitivity to subtle molecule-bonding induced changes in refractive index. The device exhibits a resonance mode around 1550 nm wavelength and provides an index sensitivity of 720 nm/RIU. Biosensing is conducted to detect the epidermal growth factor receptor 2 (ErbB2), a protein biomarker for early-stage breast cancer screening, by monitoring resonance wavelength shifts in response to specific analyte-ligand binding events at the metasurface. The limit of detection of the device is 0.7 ng mL -1 for ErbB2. Copyright © 2018 Elsevier B.V. All rights reserved.

  6. The Discovery of Novel Biomarkers Improves Breast Cancer Intrinsic Subtype Prediction and Reconciles the Labels in the METABRIC Data Set.

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    Heloisa Helena Milioli

    Full Text Available The prediction of breast cancer intrinsic subtypes has been introduced as a valuable strategy to determine patient diagnosis and prognosis, and therapy response. The PAM50 method, based on the expression levels of 50 genes, uses a single sample predictor model to assign subtype labels to samples. Intrinsic errors reported within this assay demonstrate the challenge of identifying and understanding the breast cancer groups. In this study, we aim to: a identify novel biomarkers for subtype individuation by exploring the competence of a newly proposed method named CM1 score, and b apply an ensemble learning, as opposed to the use of a single classifier, for sample subtype assignment. The overarching objective is to improve class prediction.The microarray transcriptome data sets used in this study are: the METABRIC breast cancer data recorded for over 2000 patients, and the public integrated source from ROCK database with 1570 samples. We first computed the CM1 score to identify the probes with highly discriminative patterns of expression across samples of each intrinsic subtype. We further assessed the ability of 42 selected probes on assigning correct subtype labels using 24 different classifiers from the Weka software suite. For comparison, the same method was applied on the list of 50 genes from the PAM50 method.The CM1 score portrayed 30 novel biomarkers for predicting breast cancer subtypes, with the confirmation of the role of 12 well-established genes. Intrinsic subtypes assigned using the CM1 list and the ensemble of classifiers are more consistent and homogeneous than the original PAM50 labels. The new subtypes show accurate distributions of current clinical markers ER, PR and HER2, and survival curves in the METABRIC and ROCK data sets. Remarkably, the paradoxical attribution of the original labels reinforces the limitations of employing a single sample classifiers to predict breast cancer intrinsic subtypes.

  7. The Discovery of Novel Biomarkers Improves Breast Cancer Intrinsic Subtype Prediction and Reconciles the Labels in the METABRIC Data Set.

    Science.gov (United States)

    Milioli, Heloisa Helena; Vimieiro, Renato; Riveros, Carlos; Tishchenko, Inna; Berretta, Regina; Moscato, Pablo

    2015-01-01

    The prediction of breast cancer intrinsic subtypes has been introduced as a valuable strategy to determine patient diagnosis and prognosis, and therapy response. The PAM50 method, based on the expression levels of 50 genes, uses a single sample predictor model to assign subtype labels to samples. Intrinsic errors reported within this assay demonstrate the challenge of identifying and understanding the breast cancer groups. In this study, we aim to: a) identify novel biomarkers for subtype individuation by exploring the competence of a newly proposed method named CM1 score, and b) apply an ensemble learning, as opposed to the use of a single classifier, for sample subtype assignment. The overarching objective is to improve class prediction. The microarray transcriptome data sets used in this study are: the METABRIC breast cancer data recorded for over 2000 patients, and the public integrated source from ROCK database with 1570 samples. We first computed the CM1 score to identify the probes with highly discriminative patterns of expression across samples of each intrinsic subtype. We further assessed the ability of 42 selected probes on assigning correct subtype labels using 24 different classifiers from the Weka software suite. For comparison, the same method was applied on the list of 50 genes from the PAM50 method. The CM1 score portrayed 30 novel biomarkers for predicting breast cancer subtypes, with the confirmation of the role of 12 well-established genes. Intrinsic subtypes assigned using the CM1 list and the ensemble of classifiers are more consistent and homogeneous than the original PAM50 labels. The new subtypes show accurate distributions of current clinical markers ER, PR and HER2, and survival curves in the METABRIC and ROCK data sets. Remarkably, the paradoxical attribution of the original labels reinforces the limitations of employing a single sample classifiers to predict breast cancer intrinsic subtypes.

  8. Genomic scars as biomarkers of homologous recombination deficiency and drug response in breast and ovarian cancers.

    Science.gov (United States)

    Watkins, Johnathan A; Irshad, Sheeba; Grigoriadis, Anita; Tutt, Andrew N J

    2014-06-03

    Poly (ADP-ribose) polymerase (PARP) inhibitors and platinum-based chemotherapies have been found to be particularly effective in tumors that harbor deleterious germline or somatic mutations in the BRCA1 or BRCA2 genes, the products of which contribute to the conservative homologous recombination repair of DNA double-strand breaks. Nonetheless, several setbacks in clinical trial settings have highlighted some of the issues surrounding the investigation of PARP inhibitors, especially the identification of patients who stand to benefit from such drugs. One potential approach to finding this patient subpopulation is to examine the tumor DNA for evidence of a homologous recombination defect. However, although the genomes of many breast and ovarian cancers are replete with aberrations, the presence of numerous factors able to shape the genomic landscape means that only some of the observed DNA abnormalities are the outcome of a cancer cell's inability to faithfully repair DNA double-strand breaks. Consequently, recently developed methods for comprehensively capturing the diverse ways in which homologous recombination deficiencies may arise beyond BRCA1/2 mutation have used DNA microarray and sequencing data to account for potentially confounding features in the genome. Scores capturing telomeric allelic imbalance, loss of heterozygosity (LOH) and large scale transition score, as well as the total number of coding mutations are measures that summarize the total burden of certain forms of genomic abnormality. By contrast, other studies have comprehensively catalogued different types of mutational pattern and their relative contributions to a given tumor sample. Although at least one study to explore the use of the LOH scar in a prospective clinical trial of a PARP inhibitor in ovarian cancer is under way, limitations that result in a relatively low positive predictive value for these biomarkers remain. Tumors whose genome has undergone one or more events that restore high

  9. Stratification of Prognosis of Triple-Negative Breast Cancer Patients Using Combinatorial Biomarkers.

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    Yong Yue

    Full Text Available Triple-negative breast cancer (TNBC is highly diverse group of cancers, and generally considered an aggressive disease associated with poor survival. Stratification of TNBC is highly desired for both prognosis and treatment decisions to identify patients who may benefit from less aggressive therapy.This study retrieved 192 consecutive non-metastasis TNBC patients who had undergone a resection of a primary tumor from 2008 to 2012. All samples were negative for ER, PR, and HER2/neu. Disease-free-survival (DFS and overall-survival (OS were evaluated for expression of immunohistochemical biomarkers (P53, Ki-67, CK5/6 and EGFR, as well as clinicopathological variables including age, tumor size, grade, lymph node status, pathologic tumor and nodal stages. The cutoff values of the basal biomarkers, EGFR and CK5/6, were estimated by time-dependent ROC curves. The prognostic values of combinatorial variables were identified by univariate and multivariate Cox analysis. Patients were stratified into different risk groups based on expression status of identified prognostic variables.Median age was 57 years (range, 28-92 years. Patients' tumor stage and nodal stage were significantly associated with OS and DFS. EGFR and CK5/6 were significant prognostic variables at cutoff points of 15% (p = 0.001, AUC = 0.723, and 50% (p = 0.006, AUC = 0.675, respectively. Multivariate Cox analysis identified five significant variables: EGFR (p = 0.016, CK5/6 (p = 0.018, Ki-67 (p = 0.048, tumor stage (p = 0.010, and nodal stage (p = 0.003. Patients were stratified into low basal (EGFR≤15% and CK5/6≤50% and high basal (EGFR>15% and/or CK5/6>50% expression groups. In the low basal expression group, patients with low expressions of Ki-67, low tumor and nodal stage had significantly better survival than those with high expressions/stages of three variables, log-rank p = 0.015 (100% vs 68% at 50 months. In the high basal expression group, patient with high basal expression

  10. Transferrin-bound proteins as potential biomarkers for advanced breast cancer patients

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    Paul Dowling

    2014-12-01

    General significance: Mass spectrometry profiling of Transferrin-bound proteins has revealed serum proteins that can distinguish between serum from advanced breast cancer patients and healthy control subjects with high confidence.

  11. Baseline immune biomarkers as predictors of MBSR(BC) treatment success in off-treatment breast cancer patients.

    Science.gov (United States)

    Reich, Richard R; Lengacher, Cecile A; Kip, Kevin E; Shivers, Steven C; Schell, Michael J; Shelton, Melissa M; Widen, Raymond H; Newton, Catherine; Barta, Michelle K; Paterson, Carly L; Farias, Jerrica R; Cox, Charles E; Klein, Thomas W

    2014-10-01

    Researchers focused on patient-centered medicine are increasingly trying to identify baseline factors that predict treatment success. Because the quantity and function of lymphocyte subsets change during stress, we hypothesized that these subsets would serve as stress markers and therefore predict which breast cancer patients would benefit most from mindfulness-based stress reduction (MBSR)-facilitated stress relief. The purpose of this study was to assess whether baseline biomarker levels predicted symptom improvement following an MBSR intervention for breast cancer survivors (MBSR[BC]). This randomized controlled trial involved 41 patients assigned to either an MBSR(BC) intervention group or a no-treatment control group. Biomarkers were assessed at baseline, and symptom change was assessed 6 weeks later. Biomarkers included common lymphocyte subsets in the peripheral blood as well as the ability of T cells to become activated and secrete cytokines in response to stimulation with mitogens. Spearman correlations were used to identify univariate relationships between baseline biomarkers and 6-week improvement of symptoms. Next, backward elimination regression models were used to identify the strongest predictors from the univariate analyses. Multiple baseline biomarkers were significantly positively related to 6-week symptom improvement. The regression models identified B-lymphocytes and interferon-γ as the strongest predictors of gastrointestinal improvement (p < .01), +CD4+CD8 as the strongest predictor of cognitive/psychological (CP) improvement (p = .02), and lymphocytes and interleukin (IL)-4 as the strongest predictors of fatigue improvement (p < .01). These results provide preliminary evidence of the potential to use baseline biomarkers as predictors to identify the patients likely to benefit from this intervention. © The Author(s) 2014.

  12. Breast Cancer

    Science.gov (United States)

    Breast cancer affects one in eight women during their lives. No one knows why some women get breast cancer, but there are many risk factors. Risks that ... who have family members with breast or ovarian cancer may wish to be tested for the genes. ...

  13. Multiple Biomarker Panels for Early Detection of Breast Cancer in Peripheral Blood

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    Fan Zhang

    2013-01-01

    Full Text Available Detecting breast cancer at early stages can be challenging. Traditional mammography and tissue microarray that have been studied for early breast cancer detection and prediction have many drawbacks. Therefore, there is a need for more reliable diagnostic tools for early detection of breast cancer due to a number of factors and challenges. In the paper, we presented a five-marker panel approach based on SVM for early detection of breast cancer in peripheral blood and show how to use SVM to model the classification and prediction problem of early detection of breast cancer in peripheral blood. We found that the five-marker panel can improve the prediction performance (area under curve in the testing data set from 0.5826 to 0.7879. Further pathway analysis showed that the top four five-marker panels are associated with signaling, steroid hormones, metabolism, immune system, and hemostasis, which are consistent with previous findings. Our prediction model can serve as a general model for multibiomarker panel discovery in early detection of other cancers.

  14. miRNA as potential biomarkers of breast cancer in the Lebanese population and in young women: a pilot study.

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    Farah J Nassar

    Full Text Available Relative to western populations, the percentage of women diagnosed with breast cancer at a young age in Lebanon is high. While the younger age of the Lebanese population compared to the West certainly contributes to this difference, potential genetic, reproductive and/or biological factors likely play an important role. The objective of this study is to investigate the contribution of miRNAs in this setting through the analysis of the expression of five reported dysregulated miRNAs, miR-148b, miR-10b, miR-21, miR-221, and miR-155 in 20 normal and 57 cancerous breast tissues from Lebanese breast cancer patients. After finding their relative expression by quantitative reverse transcription real time PCR, the results were analyzed with respect to the patients' clinical and histopathology presentations. Compared to normal breast tissues, significant upregulation of miR-155, miR-21 and miR-148b, notable downregulation of miR-10b and non-significant expression of miR-221 were observed in tumor tissues. Moreover, miR-10b was significantly underexpressed in estrogen/progesterone receptor (ER/PR negative tumors relative to ER/PR positive tumor tissues. miR-155 was also significantly overexpressed in postmenopausal patients and in those of age at diagnosis greater than 40 years old as well as in PR negative or in human epidermal growth factor 2 (Her2 positive tissues. This study is the first one to report miRNA expression patterns in Lebanese breast cancer patients. We found that differential miRNA expression in breast cancer could be variable between Lebanese and Western populations. miR-10b was positively correlated with the ER and PR status and miR-155 could be a noteworthy biomarker for the menopausal state, age at diagnosis, PR and Her2 status. Hence, miRNA can be used as biomarkers for early breast cancer detection.

  15. Pilot study demonstrating potential association between breast cancer image-based risk phenotypes and genomic biomarkers

    Science.gov (United States)

    Li, Hui; Giger, Maryellen L.; Sun, Chang; Ponsukcharoen, Umnouy; Huo, Dezheng; Lan, Li; Olopade, Olufunmilayo I.; Jamieson, Andrew R.; Brown, Jeremy Bancroft; Rienzo, Anna Di

    2014-01-01

    Purpose: In this pilot study, the authors examined associations between image-based phenotypes and genomic biomarkers. The potential genetic contribution of UGT2B genes to interindividual variation in breast density and mammographic parenchymal patterns is demonstrated by performing an association study between image-based phenotypes and genomic biomarkers [single-nucleotide polymorphism (SNP) genotypes]. Methods: This candidate-gene approach study included 179 subjects for whom both mammograms and blood DNA samples had been obtained. The full-field digital mammograms were acquired using a GE Senographe 2000D FFDM system (12-bit; 0.1 mm-pixel size). Regions-of-interest, 256 × 256 pixels in size, selected from the central breast region behind the nipple underwent computerized image analysis to yield image-based phenotypes of mammographic density and parenchymal texture patterns. SNP genotyping was performed using a Sequenom MassArray System. One hundred twenty three SNPs with minor allele frequency above 5% were genotyped for the UGT2B gene clusters, and used in the study. The association between the image-based phenotypes and genomic biomarkers was assessed with the Pearson correlation coefficient via the PLINK software, and included permutation and correction for multiple SNP comparisons. Results: From the phenotype-genotype association analysis, a parenchyma texture coarseness feature was found to be correlated with SNP rs451632 after multiple test correction for the multiple SNPs (p = 0.022). The power law β, which is used to characterize the frequency component of texture patterns, was found to be correlated with SNP rs4148298 (p = 0.035). Conclusions: The authors’ results indicate that UGT2B gene variation may contribute to interindividual variation in mammographic parenchymal patterns and breast density. Understanding the relationship between image-based phenotypes and genomic biomarkers may help understand the biologic mechanism for image

  16. Identifying gaps and relative opportunities for discovering membrane proteomic biomarkers of triple-negative breast cancer as a translational priority

    Directory of Open Access Journals (Sweden)

    Bhooma Venkatraman

    2016-01-01

    Full Text Available Triple-negative breast cancer (TNBC remains a significant clinical and scientific challenge. The classification of TNBC is based on the lack of expression of the human epidermal growth factor 2, the estrogen receptor, and the progesterone receptor. TNBC accounts for more than 20% of all breast cancers (BCs, has a poorer prognosis compared to other BC subtypes, and has no targeted therapeutics. Primarily, this review focuses on the heterogeneity of BC and the importance of molecular subtyping for the accurate classification of TNBC. Further, it seeks to identify the molecular "omic" gaps in subtyping TNBC and the role of membrane protein biomarkers that could potentially advance clinical and translational research in BC.

  17. Impedimetric detection of mutant p53 biomarker-driven metastatic breast cancers under hyposmotic pressure.

    Directory of Open Access Journals (Sweden)

    Menglu Shi

    Full Text Available In cancer cells, the oncogenic mutant p53 (mtp53 protein is present at high levels and gain-of-function (GOF activities with more expression of mtp53 proteins contribute to tumor growth and metastasis. Robust analytical approaches that probe the degree of metastasis of cancer cells in connection with the mtp53 activity will be extremely useful not only for establishing a better cancer prognosis but also understanding the fundamental mechanism of mtp53 oncogenic action. Here we assessed the influence of mtp53 in breast cancers to the mechanical property of breast cancer cells. Recently, ovarian and kidney cancer cell lines have been shown to have higher cellular elasticity as compared to normal cells assessed by monitoring the degree of deformation under hyposmotic pressure. To make fast detection in large scale, the impedance measurement was applied to monitor the swelling ratio of cells with time. The results showed that knockdown of mtp53 leads to decrease in cell swelling. In addition, by means of two types of impedimetric detection systems we consistently detected enhancement of impedance signal in mtp53-expressing breast cancer cells. Based on this observation we hypothesize that highly expressed mtp53 in metastatic mutant breast cancers can promote tumor progression by making cells more deformable and easier to spread out through extracellular matrix. The identification via the electric measurement can be accomplished within 10 minutes. All results in this report suggest that electric probing for the extent of the mtp53 expression of breast cancer cells may serve as a meaningful fingerprint for the cancer diagnostics, and this outcome will also have an important clinical implication for the development of mtp53-based targeting for tumor detection and treatment.

  18. CA 15-3: uses and limitation as a biomarker for breast cancer.

    LENUS (Irish Health Repository)

    Duffy, Michael J

    2012-02-01

    CA 15-3 which detects soluble forms of MUC-1 protein is the most widely used serum marker in patients with breast cancer. Its main use is for monitoring therapy in patients with metastatic disease. In monitoring therapy in this setting, CA 15-3 should not be used alone but measured in conjunction with diagnostic imaging, clinical history and physical examination. CA 15-3 is particularly valuable for treatment monitoring in patients that have disease that cannot be evaluated using existing radiological procedures. CA 15-3 may also be used in the postoperative surveillance of asymptomatic women who have undergone surgery for invasive breast cancer. In this setting, serial determination can provide median lead-times of 5-6 months in the early detection of recurrent\\/metastatic breast cancer. It is unclear however, whether administering systemic therapy based on this lead-time improves patient outcome. Consequently, expert panels disagree on the utility of regularly measuring CA 15-3 in the postoperative surveillance of asymptomatic women following a diagnosis of breast cancer. The main limitation of CA 15-3 as a marker for breast cancer is that serum levels are rarely increased in patients with early or localized disease.

  19. Multigene methylation in serum of sporadic Chinese female breast cancer patients as a prognostic biomarker.

    Science.gov (United States)

    Jing, Feng; Jun, Lu; Yong, Zhang; Wang, Yuping; Fei, Xie; Zhang, Jicai; Hu, Lihua

    2008-01-01

    DNA methylation is a common molecular alteration in human neoplasia and can be detected easily in the bloodstream of patients. Here, we investigated whether DNA methylation in sera is of prognostic significance in breast cancer patients. Methylation status of BRCA1, p16 and 14-3-3sigma was examined by methylation-specific PCR assay in the sera of sporadic breast cancer patients and healthy serum controls. The panel gene methylation frequencies were 29% of sporadic breast cancers for p16, 32% for BRCA1 and 82% for 14-3-3sigma; all were significantly associated with grades and estrogen receptor status. Only p16 methylation was associated with histological type. p16 and BRCA1 methylation were associated with progesterone receptor status, while 14-3-3sigma was significantly associated with lymph node metastases. Seventy percent of patients with p16 methylation showed elevated serum CEA levels; of the breast cancer patients with BRCA1 methylation, 75.8% showed elevated serum CEA levels and 69.7% showed elevated serum CA15.3 levels. When analyzing all investigated patients, multivariate analysis showed methylated BRCA1 and/or p16 serum DNA to be independently associated with poor outcome, with a relative risk of death of 6.0. Epigenetic markers in sera, especially BRCA1/p16, may be more promising targets for the diagnosis of sporadic breast cancer than previous prognostic markers. Copyright 2008 S. Karger AG, Basel.

  20. Translational database selection and multiplexed sequence capture for up front filtering of reliable breast cancer biomarker candidates.

    Directory of Open Access Journals (Sweden)

    Patrik L Ståhl

    Full Text Available Biomarker identification is of utmost importance for the development of novel diagnostics and therapeutics. Here we make use of a translational database selection strategy, utilizing data from the Human Protein Atlas (HPA on differentially expressed protein patterns in healthy and breast cancer tissues as a means to filter out potential biomarkers for underlying genetic causatives of the disease. DNA was isolated from ten breast cancer biopsies, and the protein coding and flanking non-coding genomic regions corresponding to the selected proteins were extracted in a multiplexed format from the samples using a single DNA sequence capture array. Deep sequencing revealed an even enrichment of the multiplexed samples and a great variation of genetic alterations in the tumors of the sampled individuals. Benefiting from the upstream filtering method, the final set of biomarker candidates could be completely verified through bidirectional Sanger sequencing, revealing a 40 percent false positive rate despite high read coverage. Of the variants encountered in translated regions, nine novel non-synonymous variations were identified and verified, two of which were present in more than one of the ten tumor samples.

  1. Profiling of microRNAs in tumor interstitial fluid of breast tumors – a novel resource to identify biomarkers for prognostic classification and detection of cancer

    DEFF Research Database (Denmark)

    Halvorsen, Ann Rita; Helland, Åslaug; Gromov, Pavel

    2017-01-01

    and to elucidate the cross-talk that exists among cells in a tumor microenvironment. Matched tumor interstitial fluid samples (TIF, n = 60), normal interstitial fluid samples (NIF, n = 51), corresponding tumor tissue specimens (n = 54), and serum samples (n = 27) were collected from patients with breast cancer......, and detectable microRNAs were analyzed and compared. In addition, serum data from 32 patients with breast cancer and 22 healthy controls were obtained for a validation study. To identify potential serum biomarkers of breast cancer, first the microRNA profiles of TIF and NIF samples were compared. A total of 266...

  2. Breast cancer

    Science.gov (United States)

    ... help you not feel alone. Outlook (Prognosis) New, improved treatments are helping people with breast cancer live ... carcinoma in situ Patient Instructions Breast radiation - discharge Chemotherapy - what to ask your doctor Lymphedema - self-care ...

  3. Breast Cancer Prevention

    Science.gov (United States)

    ... of Breast & Gynecologic Cancers Breast Cancer Screening Research Breast Cancer Prevention (PDQ®)–Patient Version What is prevention? Go ... from starting. Risk-reducing surgery . General Information About Breast Cancer Key Points Breast cancer is a disease in ...

  4. Large intergenic non-coding RNA-ROR as a potential biomarker for the diagnosis and dynamic monitoring of breast cancer.

    Science.gov (United States)

    Zhao, Tianhe; Wu, Lichun; Li, Xinyang; Dai, Huangmei; Zhang, Zunzhen

    2017-08-23

    Recent study has revealed that large intergenic non-coding RNA-ROR (linc-ROR) is aberrantly expressed in a number of cancers including breast cancer. However, whether circulating linc-ROR in plasma could be used for breast cancer diagnosis and dynamic monitoring is not clear. The objective of this study is to determine if plasma linc-ROR could be applied as a biomarker for the diagnosis and dynamic monitoring of breast cancer. We tested the expression levels of linc-ROR in 24 pairs of tissue samples and 96 plasma samples from breast cancer patients by quantitative real time-polymerase chain reaction (qRT-PCR), and analyzed the correlation between plasma linc-ROR levels and clinico-pathological characteristics. Receiver operating characteristic (ROC) curve was used to assess the diagnostic power of plasma linc-ROR, carcinoembryonic antigen (CEA) and carbohydrate antigen (CA)153 for breast cancer. Furthermore, we explored the monitoring values of plasma linc-ROR for breast cancer by analyzing the preoperative and postoperative plasma linc-ROR levels of the same patients. The expression levels of linc-ROR were significantly higher in breast cancer tissues and plasma than the levels in the control (PROR expression levels in plasma were correlated with lymph node metastasis (PROR was 0.758 (sensitivity 80.0%; specificity 73.3%), which was higher than CEA and CA153 values from the same patients obtained. Combination of the linc-ROR with the conventional biomarkers might produce better diagnostic ability. Additionally, the linc-ROR expression levels of plasma in postoperative patients were lower than those in preoperative patients (PROR may be a potential biomarker for the diagnosis and dynamic monitoring of breast cancer.

  5. Clinical usefulness of human epidermal growth factor receptor-2 extracellular domain as a biomarker for monitoring cancer status and predicting the therapeutic efficacy in breast cancer

    Science.gov (United States)

    Kontani, Keiichi; Kuroda, Noriyuki; Hashimoto, Shin-ichiro; Murazawa, Chisa; Norimura, Shoko; Tanaka, Hiroaki; Ohtani, Masahiro; Fujiwara-Honjo, Naomi; Kushida, Yoshio; Date, Manabu; Haba, Reiji; Houchi, Hitoshi; Yamauchi, Akira; Yokomise, Hiroyasu

    2013-01-01

    We assessed the clinical usefulness of human epidermal growth factor receptor-2 extracellular domain (HER2ECD) as a biomarker for detecting cancer and monitoring disease status and for predicting the efficacy of anticancer treatment in breast cancer. Five-hundred and eighty serum samples from 252 patients with breast cancer were examined for the concentration of HER2ECD to compare with conventional tumor markers (CEA, CA15-3, NCC-ST439 and BCA225). Also, in 19 patients with HER2-overexpressed advanced or recurrent breast cancer who were treated with trastuzumab, clinical outcomes were evaluated retrospectively to determine whether their serum HER2ECD levels predict clinical responses. The proportion of patients with elevated HER2ECD levels was 15.1%, which was compatible with those with elevated conventional marker levels. In patients with HER2-overexpressed breast cancer, the positive rate of HER2ECD was significantly higher (24.1%) than those of conventional markers (7.4–12.9%), suggesting the usefulness of HER2ECD for detecting cancer in this population. HER2-overexpressed patients responding to trastuzumab (12 of 19 patients) showed significantly higher serum HER2ECD level (p = 0.033) and longer time to progression (TTP) (p = 0.039) and overall survival (OS) (p = 0.031) than did patients not responding (seven patients). Furthermore, higher response rates were observed in patients with elevated HER2ECD levels than in patients without elevated HER2ECD levels (91.3% vs. 14.3%, p = 0.032), whereas there was no difference in survival between the two groups. The results suggest that HER2ECD is a useful biomarker not only for detecting breast cancer recurrence but also for predicting tumor responses to trastuzumab. PMID:23114645

  6. Biomedical application of fuzzy association rules for identifying breast cancer biomarkers.

    Science.gov (United States)

    Lopez, F J; Cuadros, M; Cano, C; Concha, A; Blanco, A

    2012-09-01

    Current breast cancer research involves the study of many different prognosis factors: primary tumor size, lymph node status, tumor grade, tumor receptor status, p53, and ki67 levels, among others. High-throughput microarray technologies are allowing to better understand and identify prognostic factors in breast cancer. But the massive amounts of data derived from these technologies require the use of efficient computational techniques to unveil new and relevant biomedical knowledge. Furthermore, integrative tools are needed that effectively combine heterogeneous types of biomedical data, such as prognosis factors and expression data. The objective of this study was to integrate information from the main prognostic factors in breast cancer with whole-genome microarray data to identify potential associations among them. We propose the application of a data mining approach, called fuzzy association rule mining, to automatically unveil these associations. This paper describes the proposed methodology and illustrates how it can be applied to different breast cancer datasets. The obtained results support known associations involving the number of copies of chromosome-17, HER2 amplification, or the expression level of estrogen and progesterone receptors in breast cancer patients. They also confirm the correspondence between the HER2 status predicted by different testing methodologies (immunohistochemistry and fluorescence in situ hybridization). In addition, other interesting rules involving CDC6, SOX11, and EFEMP1 genes are identified, although further detailed studies are needed to statistically confirm these findings. As part of this study, a web platform implementing the fuzzy association rule mining approach has been made freely available at: http://www.genome2.ugr.es/biofar .

  7. Identification of Novel Breast Cancer Subtype-Specific Biomarkers by Integrating Genomics Analysis of DNA Copy Number Aberrations and miRNA-mRNA Dual Expression Profiling

    Directory of Open Access Journals (Sweden)

    Dongguo Li

    2015-01-01

    Full Text Available Breast cancer is a heterogeneous disease with well-defined molecular subtypes. Currently, comparative genomic hybridization arrays (aCGH techniques have been developed rapidly, and recent evidences in studies of breast cancer suggest that tumors within gene expression subtypes share similar DNA copy number aberrations (CNA which can be used to further subdivide subtypes. Moreover, subtype-specific miRNA expression profiles are also proposed as novel signatures for breast cancer classification. The identification of mRNA or miRNA expression-based breast cancer subtypes is considered an instructive means of prognosis. Here, we conducted an integrated analysis based on copy number aberrations data and miRNA-mRNA dual expression profiling data to identify breast cancer subtype-specific biomarkers. Interestingly, we found a group of genes residing in subtype-specific CNA regions that also display the corresponding changes in mRNAs levels and their target miRNAs’ expression. Among them, the predicted direct correlation of BRCA1-miR-143-miR-145 pairs was selected for experimental validation. The study results indicated that BRCA1 positively regulates miR-143-miR-145 expression and miR-143-miR-145 can serve as promising novel biomarkers for breast cancer subtyping. In our integrated genomics analysis and experimental validation, a new frame to predict candidate biomarkers of breast cancer subtype is provided and offers assistance in order to understand the potential disease etiology of the breast cancer subtypes.

  8. ANX7 as a Bio-Marker in Prostate and Breast Cancer Progression

    Directory of Open Access Journals (Sweden)

    Meera Srivastava

    2001-01-01

    Full Text Available The ANX7 gene codes for a Ca2+-activated GTPase, which has been implicated in both exocytotic secretion in cells and control of growth. In this review, we summarize information regarding increased tumor frequency in the Anx7 knockout mice, ANX7 growth suppression of human cancer cell lines, and ANX7 expression in human tumor tissue micro-arrays. The loss of ANX7 is significant in metastatic and hormone refractory prostate cancer compared to benign prostatic hyperplasia. In addition, ANX7 expression has prognostic value for predicting survival of breast cancer patients.

  9. Detection and identification of breast cancer volatile organic compounds biomarkers using highly-sensitive single nanowire array on a chip.

    Science.gov (United States)

    Xu, Yiwen; Lee, Hyunjoong; Hu, Yushi; Huang, Jiyong; Kim, Suhwan; Yun, Minhee

    2013-07-01

    A single nanowire array on a chip with different materials of Palladium, Polypyrrole and Zinc Oxide has been fabricated using electrochemical deposition method. The fabricated single nanowire array has been demonstrated for highly sensitive and specific diagnosis of breast cancer by detecting four volatile organic compound biomarkers: Heptanal, Acetophenone, Isopropyl Myristate and 2-Propanol. The demonstrated sensing limits for Heptanal, Acetophenone, Isopropyl Myristate and 2-propanol using individual Palladium, Polypyrrole and Zinc Oxide nanowires were 8.982 ppm, 798 ppb, 134 ppm, and 129.5 ppm, respectively, and the corresponding sensitivities of resistance change were in the range of 0.3%-5% which indicated excellent sensing performance of the single nanowires. The response time for Palladium, Polypyrrole and Zinc Oxide nanowires to achieve maximum conductance change was less than 200 seconds while also illustrating excellent signal repeatability. With the principal component analysis of the resistance change versus time in each detection period of the nanowire array, the smell prints for the four volatile organic compounds biomarkers of Breast Cancer are discriminated in the 3-D plots.

  10. Identification of Potential Glycoprotein Biomarkers in Estrogen Receptor Positive (ER+ and Negative (ER- Human Breast Cancer Tissues by LC-LTQ/FT-ICR Mass Spectrometry

    Directory of Open Access Journals (Sweden)

    Suzan M. Semaan, Xu Wang, Alan G. Marshall, Qing-Xiang Amy Sang

    2012-01-01

    Full Text Available Breast cancer is the second most fatal cancer in American women. To increase the life expectancy of patients with breast cancer new diagnostic and prognostic biomarkers and drug targets must be identified. A change in the glycosylation on a glycoprotein often causes a change in the function of that glycoprotein; such a phenomenon is correlated with cancerous transformation. Thus, glycoproteins in human breast cancer estrogen receptor positive (ER+ tissues and those in the more advanced stage of breast cancer, estrogen receptor negative (ER- tissues, were compared. Glycoproteins showing differences in glycosylation were examined by 2-dimensional gel electrophoresis with double staining (glyco- and total protein staining and identified by reversed-phase nano-liquid chromatography coupled with a hybrid linear quadrupole ion trap/ Fourier transform ion cyclotron resonance mass spectrometer. Among the identified glycosylated proteins are alpha 1 acid glycoprotein, alpha-1-antitrypsin, calmodulin, and superoxide dismutase mitochondrial precursor that were further verified by Western blotting for both ER+ and ER- human breast tissues. Results show the presence of a possible glycosylation difference in alpha-1-antitrypsin, a potential tumor-derived biomarker for breast cancer progression, which was expressed highest in the ER- samples.

  11. Feasibility of a lifestyle intervention on body weight and serum biomarkers in breast cancer survivors with overweight and obesity.

    Science.gov (United States)

    Campbell, Kristin L; Van Patten, Cheri L; Neil, Sarah E; Kirkham, Amy A; Gotay, Carolyn C; Gelmon, Karen A; McKenzie, Donald C

    2012-04-01

    Physical inactivity and being overweight or obese are lifestyle factors that put breast cancer survivors at a higher risk for a cancer recurrence and/or development of other chronic diseases. Despite this, there is limited research that has identified effective lifestyle interventions aimed specifically at weight loss in breast cancer survivors. This pilot study is a single-arm experimental pre-post test design, conducted from November 2009 to July 2010, that tested the efficacy of a 24-week group-based lifestyle intervention modeled on the Diabetes Prevention Program in early stage breast cancer survivors (N=14). The intervention included 16 diet sessions led by a registered dietitian and 150 min/wk of moderate-to-vigorous exercise. Study outcome measures were completed at baseline, 24, and 36 weeks (nonintervention follow-up). The primary outcome was change in body weight, and secondary outcomes were change in body composition, aerobic fitness, dietary intake, and blood biomarkers. Overall, participants were postmenopausal women aged 54.6±8.3 years with obesity (body mass index 30.1±3.6), and had completed adjuvant cancer treatment 2 years prior. Results showed an average weight loss of 3.8±5.0 kg and a decrease in body mass index, percent body fat, and waist and hip circumferences at 24 weeks and an additional mean weight loss of 0.8±1.2 kg at 36 weeks. In exploratory analysis, participants who lost >7% body weight were older and attended a greater percentage of diet and supervised exercise sessions. There were no significant changes in any of the blood biomarkers at 24 and 36 weeks; however, the results provide a measure of expected effect size for future research studies. This pilot study demonstrated the efficacy of a lifestyle intervention based on the Diabetes Prevention Program in early stage breast cancer survivors and represents an innovative clinical intervention for dietetics practitioners to address the unmet need for programs. Copyright © 2012

  12. Breast Cancer: Treatment Options

    Science.gov (United States)

    ... Breast Cancer > Breast Cancer: Treatment Options Request Permissions Breast Cancer: Treatment Options Approved by the Cancer.Net Editorial ... as possible. Learn more about palliative care . Recurrent breast cancer If the cancer does return after treatment for ...

  13. Breast Cancer Treatment

    Science.gov (United States)

    ... of Breast & Gynecologic Cancers Breast Cancer Screening Research Breast Cancer Treatment (PDQ®)–Patient Version General Information About Breast Cancer Go to Health Professional Version Key Points Breast ...

  14. Stages of Breast Cancer

    Science.gov (United States)

    ... of Breast & Gynecologic Cancers Breast Cancer Screening Research Breast Cancer Treatment (PDQ®)–Patient Version General Information About Breast Cancer Go to Health Professional Version Key Points Breast ...

  15. Breast cancer screening

    Science.gov (United States)

    Mammogram - breast cancer screening; Breast exam - breast cancer screening; MRI - breast cancer screening ... is performed to screen women to detect early breast cancer when it is more likely to be cured. ...

  16. Intravoxel incoherent motion (IVIM histogram biomarkers for prediction of neoadjuvant treatment response in breast cancer patients

    Directory of Open Access Journals (Sweden)

    Gene Y. Cho

    Full Text Available Objective: To examine the prognostic capabilities of intravoxel incoherent motion (IVIM metrics and their ability to predict response to neoadjuvant treatment (NAT. Additionally, to observe changes in IVIM metrics between pre- and post-treatment MRI. Methods: This IRB-approved, HIPAA-compliant retrospective study observed 31 breast cancer patients (32 lesions. Patients underwent standard bilateral breast MRI along with diffusion-weighted imaging before and after NAT. Six patients underwent an additional IVIM-MRI scan 12–14 weeks after initial scan and 2 cycles of treatment. In addition to apparent diffusion coefficients (ADC from monoexponential decay, IVIM mean values (tissue diffusivity Dt, perfusion fraction fp, and pseudodiffusivity Dp and histogram metrics were derived using a biexponential model. An additional filter identified voxels of highly vascular tumor tissue (VTT, excluding necrotic or normal tissue. Clinical data include histology of biopsy and clinical response to treatment through RECIST assessment. Comparisons of treatment response were made using Wilcoxon rank-sum tests. Results: Average, kurtosis, and skewness of pseudodiffusion Dp significantly differentiated RECIST responders from nonresponders. ADC and Dt values generally increased (∼70% and VTT% values generally decreased (∼20% post-treatment. Conclusion: Dp metrics showed prognostic capabilities; slow and heterogeneous pseudodiffusion offer poor prognosis. Baseline ADC/Dt parameters were not significant predictors of response. This work suggests that IVIM mean values and heterogeneity metrics may have prognostic value in the setting of breast cancer NAT. Keywords: Breast cancer, Diffusion weighted MRI, Intravoxel incoherent motion, Neoadjuvant treatment, Response evaluation criteria in solid tumors

  17. The potential of identification of a malignancy-associated biomarker in breast cancer diagnosis and research: hTERT gene DNA methylation.

    Science.gov (United States)

    Masood, Shahla; El-Gabry, Ehab; Zhang, Chuhua; Wang, Zhiqianq

    2016-08-01

    DNA hypermethylation has been documented to be prominent at a CpG island rich region about 600 bp upstream the transcription start site of the hTERT gene using qualitative methylation specific PCR on DNA isolated from tumor cell lines. In order to assess the potential significance of this biomarker in breast cancer research and diagnosis, we explored if such findings are reproducible on surgically resected fresh breast tumor cells. Using quantitative pyrosequencing technology, we investigated and present methylation status of four CpG islands of this region in a cohort of 77 invasive breast carcinomas using normal breast tissue as controls. Globally, a significant hypermethylation in tumor cells was observed in the four CpG islands as a sum, in comparison to methylation of the normal breast tissue. Individually, certain CpG islands displayed methylation greater than 50% in about 3/4 of the 77 breast cancers, but in none of the normal breast tissue. Our results highlight the value of DNA hypermethylation in the -600 bp region of the hTERT gene as a potential marker for breast cancer diagnosis. We believe that integration of this novel, malignancy-associated molecular testing with morphology is of significant value in the accurate interpretation of small tumor sample size obtained via fine needle aspiration biopsy, ductal lavage, and nipple fluid aspirates both in clinical practice and in breast cancer research. Diagn. Cytopathol. 2016;44:670-675. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  18. Annexin A2 and its downstream IL-6 and HB-EGF as secretory biomarkers in the differential diagnosis of Her-2 negative breast cancer.

    Science.gov (United States)

    Shetty, Praveenkumar; Patil, Vidya S; Mohan, Rajashekar; D'souza, Leonard Clinton; Bargale, Anil; Patil, Basavaraj R; Dinesh, U S; Haridas, Vikram; Kulkarni, Shrirang P

    2017-07-01

    Background AnnexinA2 (AnxA2) membrane deposition has a critical role in HB-EGF shedding as well as IL-6 secretion in breast cancer cells. This autocrine cycle has a major role in cancer cell proliferation, migration and metastasis. The objective of the study is to demonstrate annexinA2-mediated autocrine regulation via HB-EGF and IL-6 in Her-2 negative breast cancer progression. Methods Secretory annexinA2, HB-EGF and IL-6 were analysed in the peripheral blood sample of Her-2 negative ( n = 20) and positive breast cancer patients ( n = 16). Simultaneously, tissue expression was analysed by immunohistochemistry. The membrane deposition of these secretory ligands and their autocrine regulation was demonstrated using triple-negative breast cancer cell line model. Results Annexina2 and HB-EGF expression are inversely correlated with Her-2, whereas IL-6 expression is seen in both Her-2 negative and positive breast cancer cells. RNA interference studies and upregulation of annexinA2 proved that annexinA2 is the upstream of this autocrine pathway. Abundant soluble serum annexinA2 is secreted in Her-2 negative breast cancer (359.28 ± 63.73 ng/mL) compared with normal (286.10 ± 70.04 ng/mL, P breast cancer phenotypes as compared with normal ( P breast cancer tissues, increased secretion compared with normal cells, and their major role in the regulation of EGFR downstream signalling makes these molecules as a potential tissue and serum biomarker and an excellent therapeutic target in Her-2 negative breast cancer.

  19. Reverse phase protein array based tumor profiling identifies a biomarker signature for risk classification of hormone receptor-positive breast cancer

    Directory of Open Access Journals (Sweden)

    Johanna Sonntag

    2014-03-01

    Full Text Available A robust subclassification of luminal breast cancer, the most common molecular subtype of human breast cancer, is crucial for therapy decisions. While a part of patients is at higher risk of recurrence and requires chemo-endocrine treatment, the other part is at lower risk and also poorly responds to chemotherapeutic regimens. To approximate the risk of cancer recurrence, clinical guidelines recommend determining histologic grading and abundance of a cell proliferation marker in tumor specimens. However, this approach assigns an intermediate risk to a substantial number of patients and in addition suffers from a high interobserver variability. Therefore, the aim of our study was to identify a quantitative protein biomarker signature to facilitate risk classification. Reverse phase protein arrays (RPPA were used to obtain quantitative expression data for 128 breast cancer relevant proteins in a set of hormone receptor-positive tumors (n = 109. Proteomic data for the subset of histologic G1 (n = 14 and G3 (n = 22 samples were used for biomarker discovery serving as surrogates of low and high recurrence risk, respectively. A novel biomarker selection workflow based on combining three different classification methods identified caveolin-1, NDKA, RPS6, and Ki-67 as top candidates. NDKA, RPS6, and Ki-67 were expressed at elevated levels in high risk tumors whereas caveolin-1 was observed as downregulated. The identified biomarker signature was subsequently analyzed using an independent test set (AUC = 0.78. Further evaluation of the identified biomarker panel by Western blot and mRNA profiling confirmed the proteomic signature obtained by RPPA. In conclusion, the biomarker signature introduced supports RPPA as a tool for cancer biomarker discovery.

  20. S100A14 is a novel independent prognostic biomarker in the triple-negative breast cancer subtype

    DEFF Research Database (Denmark)

    Ehmsen, Sidse; Hansen, Lea Tykgaard; Bak, Martin

    2015-01-01

    Triple-negative breast cancer (TNBC) represents a heterogeneous subgroup with generally poor outcome and lack of an effective targeted therapy. Prognostic or predictive biomarkers to guide treatment decisions for this group of patients are needed. To evaluate the potential of S100A14 protein...... with high S100A14 protein expression levels were significantly correlated with poor outcome in TNBC patients (p = 0.017; p = 0.038), particularly those in the basal-like subgroup (p = 0.006; p = 0.037). Importantly, TNBC patients with high S100A14 expression, but tumor-negative axillary lymph nodes (N.......024; p = 0.05). At the cellular level, S100A14 was found to be expressed in epithelial-like, but not in mesenchymal-like, TNBC cells in vitro. S100A14 is an independent prognostic factor in TNBC and a novel potential therapeutic target in TNBC....

  1. DNA biosensors based on gold nanoparticles-modified graphene oxide for the detection of breast cancer biomarkers for early diagnosis.

    Science.gov (United States)

    Saeed, Ayman Ali; Sánchez, Josep Lluís Acero; O'Sullivan, Ciara K; Abbas, Mohammed Nooredeen

    2017-12-01

    Two different DNA (ERBB2c and CD24c) modified gold nanoparticles and graphene oxide loaded on glassy carbon electrodes were prepared for early detection of breast cancer markers by electrochemical detection of HER2. Comparative study of ERBB2c and CD24c for the detection was carried out. A "sandwich-type" detection strategy was employed in this electrochemical DNA biosensor and its response was measured by amperometric detection. The electrochemical signal enhancement achieved via gold nanoparticles and grapheme oxide system allowed for sensitive detection of the breast cancer biomarker ERBB2 and the control marker CD24. The modified graphene oxide was characterised using Raman spectroscopy, UV-visible spectroscopy, Fourier transform infrared spectroscopy transmission electron microscopy, scanning electron microscopy and energy-dispersive X-ray spectroscopy. The various steps involved in the modification of a glassy carbon electrode with graphene oxide, gold nanoparticles and DNA probes, target and reporter probe were electrochemically characterised using cyclic voltammetry and electrochemical impedance spectroscopy. Using amperometric detection of a horse radish peroxidase label, detection limits of 0.16nM and 0.23nM were obtained with sensitivity 378nA/nM and 219nA/nM for ERBB2 andCD24 respectively. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Breast cancer

    CERN Multimedia

    2002-01-01

    "Cancer specialists will soon be able to compare mammograms with computerized images of breast cancer from across Europe, in a bid to improve diagnosis and treatment....The new project, known as MammoGrid, brings together computer and medical imaging experts, cancer specialists, radiologists and epidemiologists from Bristol, Oxford, Cambridge, France and Italy" (1 page).

  3. 6 Common Cancers - Breast Cancer

    Science.gov (United States)

    ... Home Current Issue Past Issues 6 Common Cancers - Breast Cancer Past Issues / Spring 2007 Table of Contents For ... slow her down. Photo: AP Photo/Brett Flashnick Breast Cancer Breast cancer is a malignant (cancerous) growth that ...

  4. Breast Cancer

    Science.gov (United States)

    ... a reduced risk of breast cancer. The Mediterranean diet focuses mostly on plant-based foods, such as fruits and vegetables, whole grains, legumes, and nuts. People who follow the Mediterranean diet choose healthy fats, such as olive oil, over ...

  5. Breast Cancer

    Science.gov (United States)

    ... disease. It’s estimated that about 10% of breast cancer cases are hereditary (run in the family). In many of these cases, you inherited a gene from your parents that has mutated (changed from ...

  6. Identification and characterization of biomarkers and their functions for Lapatinib-resistant breast cancer.

    Science.gov (United States)

    Zhang, Liang; Huang, Yi; Zhuo, Wenlei; Zhu, Yi; Zhu, Bo; Chen, Zhengtang

    2017-05-01

    Lapatinib, a novel oral dual tyrosine kinase inhibitor blocking HER1 and HER2 pathways, has presented beneficial effects on breast cancer with positive HER2. However, its efficacy is largely limited by the occurrence of acquired drug resistance. In this study, we aimed to explore the underlying molecular mechanisms of Lapatinib resistance using bioinformatics strategies. The gene expression profile of SKBR3-R (acquired Lapatinib-resistant) and SKBR3 (Lapatinib-sensitive) cell line was downloaded from gene expression omnibus database. Then, the differentially expressed genes (DEGs) were selected using dChip software. Furthermore, gene ontology (GO) and pathway enrichment analyses were carried out by using DAVID database. Finally, the protein-protein interaction network was constructed, and the hub genes in the network were analyzed by using STRING database. A total of 300 DEGs, such as HSPA5, MAP1LC3A and RASSF2, were screened out. GO functional enrichment analysis showed that the genes were associated with cell membrane component-related, stimulus-related and binding-related items. KEGG pathway analysis indicated that three dysfunctional pathways, including PPAR signaling pathway, cytokine-cytokine receptor interaction and pathways in cancer, were enriched. Protein-protein interaction network construction revealed that some hub genes, such as PPARG, TGFBI, TGFBR2, TIMP1, CTGF, UBA52 and JUN, might have an association with Lapatinib resistance. The present study offered new insights into the molecular mechanisms of Lapatinib resistance and identified a series of important hub genes that have the potential to be the targets for treatment of Lapatinib-resistant breast cancer.

  7. Immunohistochemical determination of the miR-1290 target arylamine N-acetyltransferase 1 (NAT1) as a prognostic biomarker in breast cancer.

    Science.gov (United States)

    Endo, Yumi; Yamashita, Hiroko; Takahashi, Satoru; Sato, Shinya; Yoshimoto, Nobuyasu; Asano, Tomoko; Hato, Yukari; Dong, Yu; Fujii, Yoshitaka; Toyama, Tatsuya

    2014-12-20

    There are many molecular differences between estrogen receptor α (ERα)-positive and ER-negative breast cancers. Recent analyses have shown that the former can be divided into two subtypes, luminal A and luminal B. These differ in response to endocrine therapy and chemotherapy, and in prognosis. In a previous study, we found that microRNA (miR)-1290 that was significantly down-regulated in luminal A tumors and its potential target arylamine N-acetyltransferase 1 (NAT1). The aim of the present study was to determine whether NAT1 is a bona fide target of miR-1290, and to investigate the impact of NAT1 on breast cancer prognosis. Luciferase reporter assays were employed to validate NAT1 as a putative miR-1290 target gene. Expression of NAT1, ERα, progesterone receptor (PgR) and HER2 was analyzed in 394 breast cancer samples by immunohistochemistry. NAT1 was confirmed to be a direct target of miR-1290. Levels of expression of NAT1 were positively correlated with those of ERα (P targets the NAT1 3'-UTR and that NAT1 protein expression is correlated with improved OS of breast cancer patients. NAT1 is a possible prognostic biomarker for lymph node-positive breast cancer. Thus, miR-1290 and its target NAT1 are associated with important characteristics of breast cancer.

  8. Green Tea and Breast Cancer

    Science.gov (United States)

    Wu, Anna H; Butler, Lesley M

    2014-01-01

    The identification of modifiable lifestyle factors that could reduce the risk of breast cancer is a research priority. Despite the enormous chemo preventive potential of green tea and compelling evidence from animal studies, its role in breast cancer development in humans is still unclear. Part of the uncertainty is related to the relatively small number of epidemiological studies on green tea and breast cancer and that the overall results from case-control studies and prospective cohort studies are discordant. In addition, the mechanisms by which green tea intake may influence risk of breast cancer in humans remains not well studied. We review the human studies that have evaluated the relationship between green tea intake and four biomarkers (sex steroid hormones, mammographic density, insulin-like growth factor, adiponectin) that are believed to be important in breast cancer development. Results from these biomarker studies are also inconclusive. Limitations of human studies and areas of further investigations are discussed. PMID:21538855

  9. Diagnostic and prognostic epigenetic biomarkers in cancer.

    Science.gov (United States)

    Costa-Pinheiro, Pedro; Montezuma, Diana; Henrique, Rui; Jerónimo, Carmen

    2015-01-01

    Growing cancer incidence and mortality worldwide demands development of accurate biomarkers to perfect detection, diagnosis, prognostication and monitoring. Urologic (prostate, bladder, kidney), lung, breast and colorectal cancers are the most common and despite major advances in their characterization, this has seldom translated into biomarkers amenable for clinical practice. Epigenetic alterations are innovative cancer biomarkers owing to stability, frequency, reversibility and accessibility in body fluids, entailing great potential of assay development to assist in patient management. Several studies identified putative epigenetic cancer biomarkers, some of which have been commercialized. However, large multicenter validation studies are required to foster translation to the clinics. Herein we review the most promising epigenetic detection, diagnostic, prognostic and predictive biomarkers for the most common cancers.

  10. Risks of Breast Cancer Screening

    Science.gov (United States)

    ... of Breast & Gynecologic Cancers Breast Cancer Screening Research Breast Cancer Screening (PDQ®)–Patient Version What is screening? ... cancer screening: Cancer Screening Overview General Information About Breast Cancer Key Points Breast cancer is a disease ...

  11. Prevalence of Prognostic Biomarkers in Archival Specimens and Breast Cancer Survival Among White, Black, and Asian Women.

    Science.gov (United States)

    1998-06-01

    J.P., Brumberg , D.J., and Berger, N.A. Socioeconomic factors and race in breast cancer recurrence and survival. Am. J. Epidemiol. 135:609-618, 1992...13. Gordon NH, Crowe JP, Brumberg DJ, Berger NA. Socioeconomic factors and race in breast cancer recurrence and survival. Am J Epidemiol. 1992; 135

  12. Epidemiology of Breast Cancer

    OpenAIRE

    南, 優子; ミナミ, ユウコ; MINAMI, Yuko

    2007-01-01

    During recent decades, breast cancer incidence has been increasing in Japan. Epidemiological studies have clarified the trend in breast cancer incidence and identified risk factors for breast cancer. Established risk factors for breast cancer include early age at menarche, late age at first birth, low parity, postmenopausal obesity, family history of breast cancer, and history of benign breast disease. Breast-feeding and physical activity may also be associated with breast cancer risk. Detail...

  13. Toxic elements as biomarkers for breast cancer: a meta-analysis study

    Directory of Open Access Journals (Sweden)

    Jouybari L

    2018-01-01

    Full Text Available Leila Jouybari,1 Marzieh Saei Ghare Naz,2 Akram Sanagoo,1 Faezeh Kiani,3 Fatemeh Sayehmiri,4 Kourosh Sayehmiri,5 Ali Hasanpour Dehkordi6 1Nursing Research Center, Goletsan University of Medical Sciences, Gorgan, Iran; 2Student Research Committee, School of Nursing and Midwifery, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 3Student Research Committee, Ilam University of Medical Sciences, Ilam, Iran; 4Proteomics Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 5Department of Social Medicine, School of Medicine, Ilam University of Medical Sciences, Ilam, Iran; 6Department of Medical Surgical, Nursing and Midwifery, Shahrekord University of Medical Sciences, Shahrekord, Iran Aims and background: Breast cancer (BC is responsible for a large proportion of incidence of cancer in the world. Identifying the risk factors contributing to the incidence of BC is crucial to find efficient preventive and management strategies for this disease. Several studies have examined Arsenic (As, Cadmium (Cd, and Nickel (Ni as risk factors for BC. The present study aimed at studying the link between As, Cd, and Ni concentrations and BC by using a meta-analysis.Materials and methods: All case–control studies addressing the relationship between As, Cd, and Ni concentrations with BC were identified through electronic search databases (­Scopus, ISI Web of Science, PubMed, EmBase, and Cochrane Library. The relevant data obtained from these papers were analyzed by a random-effects model. The heterogeneity of studies was secured by using I2 index. Funnel plots and Egger’s test were used to examine publication bias.Results: In the present study, due to different measurement methods used for measuring As, Cd, and Ni, the concentration of these elements was measured in various subgroups (1: plasma, 2: breast tissue, and 3: scalp hair and nail of individuals with BC and healthy subjects. The overall integration of data from the 3

  14. Frequency and Circadian Timing of Eating May Influence Biomarkers of Inflammation and Insulin Resistance Associated with Breast Cancer Risk.

    Directory of Open Access Journals (Sweden)

    Catherine R Marinac

    Full Text Available Emerging evidence suggests that there is interplay between the frequency and circadian timing of eating and metabolic health. We examined the associations of eating frequency and timing with metabolic and inflammatory biomarkers putatively associated with breast cancer risk in women participating in the National Health and Nutrition Examination 2009-2010 Survey. Eating frequency and timing variables were calculated from 24-hour food records and included (1 proportion of calories consumed in the evening (5 pm-midnight, (2 number of eating episodes per day, and (3 nighttime fasting duration. Linear regression models examined each eating frequency and timing exposure variable with C-reactive protein (CRP concentrations and the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR. Each 10 percent increase in the proportion of calories consumed in the evening was associated with a 3 percent increase in CRP. Conversely, eating one additional meal or snack per day was associated with an 8 percent reduction in CRP. There was a significant interaction between proportion of calories consumed in the evening and fasting duration with CRP (p = 0.02. A longer nighttime fasting duration was associated with an 8 percent lower CRP only among women who ate less than 30% of their total daily calories in the evening (p = 0.01. None of the eating frequency and timing variables were significantly associated with HOMA-IR. These findings suggest that eating more frequently, reducing evening energy intake, and fasting for longer nightly intervals may lower systemic inflammation and subsequently reduce breast cancer risk. Randomized trials are needed to validate these associations.

  15. Inflammatory biomarkers and cancer

    DEFF Research Database (Denmark)

    Rasmussen, Line Jee Hartmann; Schultz, Martin; Gaardsting, Anne

    2017-01-01

    soluble urokinase plasminogen activator receptor (suPAR) and the pattern recognition receptors (PRRs) pentraxin-3, mannose-binding lectin, ficolin-1, ficolin-2 and ficolin-3. We aimed to evaluate these biomarkers and compare their diagnostic ability to classical biomarkers for diagnosing cancer......In Denmark, patients with serious nonspecific symptoms and signs of cancer (NSSC) are referred to the diagnostic outpatient clinics (DOCs) where an accelerated cancer diagnostic program is initiated. Various immunological and inflammatory biomarkers have been associated with cancer, including...... in patients with NSSC. Patients were included from the DOC, Department of Infectious Diseases, Copenhagen University Hospital Hvidovre. Patients were given a final diagnosis based on the combined results from scans, blood work and physical examination. Weight loss, Charlson score and previous cancer were...

  16. Benign Breast Disease: Toward Molecular Prediction of Breast Cancer Risk

    Science.gov (United States)

    2006-06-01

    at the initial biopsy, the strength of the family history, meno- pausal status, and histologic findings of the biop- sy, as compared with expected...breast cancers for 646/758 (85%) of the cases. We assessed the significance of benign histology in predicting risk of future breast cancer, examining...TERMS Benign Breast Disease, Biomarkers, Histology , Breast Cancer 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF

  17. Profiling of microRNAs in tumor interstitial fluid of breast tumors - a novel resource to identify biomarkers for prognostic classification and detection of cancer.

    Science.gov (United States)

    Halvorsen, Ann Rita; Helland, Åslaug; Gromov, Pavel; Wielenga, Vera Timmermans; Talman, Maj-Lis Møller; Brunner, Nils; Sandhu, Vandana; Børresen-Dale, Anne-Lise; Gromova, Irina; Haakensen, Vilde D

    2017-02-01

    It has been hypothesized based on accumulated data that a class of small noncoding RNAs, termed microRNAs, are key factors in intercellular communication. Here, microRNAs present in interstitial breast tumor fluids have been analyzed to identify relevant markers for a diagnosis of breast cancer and to elucidate the cross-talk that exists among cells in a tumor microenvironment. Matched tumor interstitial fluid samples (TIF, n = 60), normal interstitial fluid samples (NIF, n = 51), corresponding tumor tissue specimens (n = 54), and serum samples (n = 27) were collected from patients with breast cancer, and detectable microRNAs were analyzed and compared. In addition, serum data from 32 patients with breast cancer and 22 healthy controls were obtained for a validation study. To identify potential serum biomarkers of breast cancer, first the microRNA profiles of TIF and NIF samples were compared. A total of 266 microRNAs were present at higher level in the TIF samples as compared to normal counterparts. Sixty-one of these microRNAs were present in > 75% of the serum samples and were subsequently tested in a validation set. Seven of the 61 microRNAs were associated with poor survival, while 23 were associated with the presence of immune cells and adipocytes. To our knowledge, these data demonstrate for the first time that profiling of microRNAs in TIF can identify novel biomarkers for the prognostic classification and detection of breast cancer. In addition, the present findings demonstrate that microRNAs may represent the cross-talk that occurs between tumor cells and their surrounding stroma. © 2016 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.

  18. Cell-free DNA detected by "liquid biopsy" as a potential prognostic biomarker in early breast cancer.

    Science.gov (United States)

    Maltoni, Roberta; Casadio, Valentina; Ravaioli, Sara; Foca, Flavia; Tumedei, Maria Maddalena; Salvi, Samanta; Martignano, Filippo; Calistri, Daniele; Rocca, Andrea; Schirone, Alessio; Amadori, Dino; Bravaccini, Sara

    2017-03-07

    As conventional biomarkers for defining breast cancer (BC) subtypes are not always capable of predicting prognosis, search for new biomarkers which can be easily detected by liquid biopsy is ongoing. It has long been known that cell-free DNA (CF-DNA) could be a promising diagnostic and prognostic marker in different tumor types, although its prognostic value in BC is yet to be confirmed. This retrospective study evaluated the prognostic role of CF-DNA quantity and integrity of HER2, MYC, BCAS1 and PI3KCA, which are frequently altered in BC. We collected 79 serum samples before surgery from women at first diagnosis of BC at Forlì Hospital (Italy) from 2002 to 2010. Twenty-one relapsed and 58 non-relapsed patients were matched by subtype and age. Blood samples were also collected from 10 healthy donors. All samples were analyzed by Real Time PCR for CF-DNA quantity and integrity of all oncogenes. Except for MYC, BC patients showed significantly higher median values of CF-DNA quantity (ng) than healthy controls, who had higher integrity and lower apoptotic index. A difference nearing statistical significance was observed for HER2 short CF-DNA (p = 0.078, AUC value: 0.6305). HER2 short CF-DNA showed an odds ratio of 1.39 for disease recurrence with p = 0.056 (95% CI 0.991-1.973). Our study suggests that CF-DNA detected as liquid biopsy could have great potential in clinical practice once demonstration of its clinical validity and utility has been provided by prospective studies with robust assays.

  19. Breast Cancer Overview

    Science.gov (United States)

    ... are here Home > Types of Cancer > Breast Cancer Breast Cancer This is Cancer.Net’s Guide to Breast Cancer. Use the menu below to choose the Overview/ ... social workers, and patient advocates. Cancer.Net Guide Breast Cancer Introduction Statistics Medical Illustrations Risk Factors and Prevention ...

  20. Breast Cancer -- Male

    Science.gov (United States)

    ... Home > Types of Cancer > Breast Cancer in Men Breast Cancer in Men This is Cancer.Net’s Guide to Breast Cancer in Men. Use the menu below to choose ... social workers, and patient advocates. Cancer.Net Guide Breast Cancer in Men Introduction Statistics Risk Factors and Prevention ...

  1. Breast Cancer

    Science.gov (United States)

    ... the Mediterranean diet choose healthy fats, such as olive oil, over butter and fish instead of red meat. Breast cancer risk reduction for women with a high risk If your doctor has assessed your family history and determined that you have other factors, such ...

  2. Blood-based DNA methylation as biomarker for breast cancer: a systematic review.

    Science.gov (United States)

    Tang, Qiuqiong; Cheng, Jie; Cao, Xue; Surowy, Harald; Burwinkel, Barbara

    2016-01-01

    Multiple studies have investigated global DNA methylation profiles and gene-specific DNA methylation in blood-based DNA to develop powerful screening markers for cancer. This systematic review summarizes the current evidence on methylation studies that investigated methylation level of blood-derived DNA of breast cancer (BC) patients in comparison to healthy controls by conducting a systematic literature review in PubMed and Web of Science. Essential results, such as methylation levels of BC cases and healthy controls, p values, and odds ratios, were extracted from these studies by two investigators independently. Overall, 45 publications met the inclusion criteria for this review. DNA from whole blood, as well as cell-free DNA (cfDNA) from serum or plasma, was used in these studies. The most common method used for measuring global DNA methylation was the investigation of repetitive elements as surrogates and the application of array-based genome-wide methylation analysis. For measuring gene-specific methylation level, methylation-specific PCR and pyrosequencing were the most frequently used methods. Epigenome-wide blood DNA hypomethylation in BC patients were reported in several studies; however, the evidence is still not conclusive. The most frequently investigated gene in whole blood was BRCA1, which was found more frequently methylated in patients compared to controls. RASSF1A was the most widely investigated gene in cfDNA of serum or plasma, which was also found more frequently methylated in patients compared to controls. Several of the eligible studies reported the associations of global hypomethylation and increased BC risk. Studies investigated associations between gene-specific methylation and BC risk, while got heterogeneous results. But two studies reported that hypermethylation of ATM gene was associated with increased BC risk, which suggest the potential use of this gene for BC risk stratification. Overall, our review suggests the possibility of using

  3. Biomarkers of cancer cachexia.

    Science.gov (United States)

    Loumaye, Audrey; Thissen, Jean-Paul

    2017-12-01

    Cachexia is a complex multifactorial syndrome, characterized by loss of skeletal muscle and fat mass, which affects the majority of advanced cancer patients and is associated with poor prognosis. Interestingly, reversing muscle loss in animal models of cancer cachexia leads to prolong survival. Therefore, detecting cachexia and maintaining muscle mass represent a major goal in the care of cancer patients. However, early diagnosis of cancer cachexia is currently limited for several reasons. Indeed, cachexia development is variable according to tumor and host characteristics. In addition, safe, accessible and non-invasive tools to detect skeletal muscle atrophy are desperately lacking in clinical practice. Finally, the precise molecular mechanisms and the key players involved in cancer cachexia remain poorly characterized. The need for an early diagnosis of cancer cachexia supports therefore the quest for a biomarker that might reflect skeletal muscle atrophy process. Current research offers different promising ways to identify such a biomarker. Initially, the quest for a biomarker of cancer cachexia has mostly focused on mediators of muscle atrophy, produced by both tumor and host, in an attempt to define new therapeutic approaches. In another hand, molecules released by the muscle into the circulation during the atrophy process have been also considered as potential biomarkers. More recently, several "omics" studies are emerging to identify new muscular or circulating markers of cancer cachexia. Some genetic markers could also contribute to identify patients more susceptible to develop cachexia. This article reviews our current knowledge regarding potential biomarkers of cancer cachexia. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  4. BAG-1 as a biomarker in early breast cancer prognosis: a systematic review with meta-analyses.

    Science.gov (United States)

    Papadakis, E S; Reeves, T; Robson, N H; Maishman, T; Packham, G; Cutress, R I

    2017-06-06

    The co-chaperone protein Bcl-2-associated athanogene-1 (BAG-1) is overexpressed in breast cancer and has been incorporated in the oncotype DX and PAM50 breast cancer prognostic assays. Bcl-2-associated athanogene-1 exists as multiple protein isoforms that interact with diverse partners, including chaperones Hsc70/Hsp70, Ser/Thr kinase Raf-1 and Bcl-2, to promote cancer cell survival. The BAG-1L isoform specifically binds to and increases the transcriptional activity of oestrogen receptor in cells, and in some, but not all studies, BAG-1 expression is predictive of clinical outcome in breast cancer. A systematic review of published studies reporting BAG-1 (mRNA and/or protein) expression and clinical outcome in early breast cancer. The REporting Recommendations for Tumour MARKer and Prognostic Studies (REMARK) criteria were used as a template against which data were assessed. Meta-analyses were performed for studies that provided a hazard ratio and 95% confidence intervals for clinical outcomes including disease-free survival or breast cancer-specific survival from univariate analysis. Eighteen studies used differing methodologies and reported on differing outcomes. Meta-analyses were only possible on results from a subset of reported studies. Meta-analyses suggested improved outcome with high BAG-1 mRNA and high BAG-1 nuclear expression by immunohistochemisty. Increased levels of BAG-1 are associated with better breast cancer outcomes.

  5. BAG-1 as a biomarker in early breast cancer prognosis: a systematic review with meta-analyses

    Science.gov (United States)

    Papadakis, E S; Reeves, T; Robson, N H; Maishman, T; Packham, G; Cutress, R I

    2017-01-01

    Background: The co-chaperone protein Bcl-2-associated athanogene-1 (BAG-1) is overexpressed in breast cancer and has been incorporated in the oncotype DX and PAM50 breast cancer prognostic assays. Bcl-2-associated athanogene-1 exists as multiple protein isoforms that interact with diverse partners, including chaperones Hsc70/Hsp70, Ser/Thr kinase Raf-1 and Bcl-2, to promote cancer cell survival. The BAG-1L isoform specifically binds to and increases the transcriptional activity of oestrogen receptor in cells, and in some, but not all studies, BAG-1 expression is predictive of clinical outcome in breast cancer. Methods: A systematic review of published studies reporting BAG-1 (mRNA and/or protein) expression and clinical outcome in early breast cancer. The REporting Recommendations for Tumour MARKer and Prognostic Studies (REMARK) criteria were used as a template against which data were assessed. Meta-analyses were performed for studies that provided a hazard ratio and 95% confidence intervals for clinical outcomes including disease-free survival or breast cancer-specific survival from univariate analysis. Results: Eighteen studies used differing methodologies and reported on differing outcomes. Meta-analyses were only possible on results from a subset of reported studies. Meta-analyses suggested improved outcome with high BAG-1 mRNA and high BAG-1 nuclear expression by immunohistochemisty. Conclusions: Increased levels of BAG-1 are associated with better breast cancer outcomes. PMID:28510570

  6. Image-Based Biomarker of Breast Cancer Risk: Analysis of Risk Disparity Among Minority Populations

    Science.gov (United States)

    2011-03-01

    brachytherapy , and other special techniques. ------------------------------------------------------------------------------------ DSUPENN Breast...simulated skin and Cooper’s ligaments. We designed and implemented the new method in Matlab and analyzed its asymptotic spatial and temporal complexity. We

  7. Male Breast Cancer

    Science.gov (United States)

    Although breast cancer is much more common in women, men can get it too. It happens most often to men between ... 60 and 70. Breast lumps usually aren't cancer. However, most men with breast cancer have lumps. ...

  8. Breast Cancer Trends

    Science.gov (United States)

    ... 2011 Funding: Increasing Awareness and Support Among Young Women with Breast Cancer Funding: Young Breast Cancer Survivors Funding: Breast Cancer Genomics Statistics Rates by Race and Ethnicity Rates by State ...

  9. Breast Cancer Surgery

    Science.gov (United States)

    FACTS FOR LIFE Breast Cancer Surgery The goal of breast cancer surgery is to remove the whole tumor from the breast. Some lymph nodes ... might still be in the body. Types of breast cancer surgery There are two types of breast cancer ...

  10. Surface plasmon resonance immunosensor for ErbB2 breast cancer biomarker determination in human serum and raw cancer cell lysates.

    Science.gov (United States)

    Eletxigerra, Unai; Martinez-Perdiguero, Josu; Barderas, Rodrigo; Pingarrón, José M; Campuzano, Susana; Merino, Santos

    2016-01-28

    A highly sensitive surface plasmon resonance (SPR) immunosensor for the important ErbB2 breast cancer biomarker has been developed. Optimization of the assay has been carried out, including signal enhancement employing gold nanoparticles (GNPs). The effect of the signal amplification of the GNPs has been also studied. The assay has been tested with clinically relevant matrices. Results in 50% human serum yielded a LOD of 180 pg mL(-1) which is a concentration 83 times lower than the clinical cut-off. Raw lysates from model breast cancer cell lines (SK-BR-3, MCF-7 and MDA-MB-436) have been also assayed and higher quantities of the ErbB2 protein were clearly observed in the ErbB2 over-expressing case (SK-BR-3). The results confirmed that the simple and highly sensitive SPR immunosensor represents a feasible tool for ErbB2 detection. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Breast cancer in pregnancy.

    Science.gov (United States)

    Krishna, Iris; Lindsay, Michael

    2013-09-01

    Pregnancy-associated breast cancer is defined as breast cancer diagnosed during pregnancy or in the first postpartum year. Breast cancer is one of the more common malignancies to occur during pregnancy and, as more women delay childbearing, the incidence of breast cancer in pregnancy is expected to increase. This article provides an overview of diagnosis, staging, and treatment of pregnancy-associated breast cancer. Recommendations for management of breast cancer in pregnancy are discussed. Copyright © 2013 Elsevier Inc. All rights reserved.

  12. Cancer and molecular biomarkers of phase 2

    DEFF Research Database (Denmark)

    Dalhoff, Kim; Enghusen Poulsen, Henrik

    2005-01-01

    Associations between genotypes of phase 2 enzymes and cancer risk are extracted from epidemiological studies, namely case-control studies. Variant alleles in glutathione S-transferase (GST), UDP-glucuronosyltransferase (UGT), sulfotransferase (SULT), and N-acetyltransferase (NAT) have been used...... as molecular genetic biomarkers of risk. GSTM(my)1 has been associated with an increased risk of colorectal cancer, lung cancer, and bladder cancer and GSTP(pi)1 with prostate cancer. UGT1A1*28 and *37 are both associated with an increased risk of breast cancer as is SULT1A1*2. The presence of UGT1A1......*28 results in an increased risk of ovarian cancer and NAT2 of colorectal and lung cancer. A high frequency of SULT1A1*1 has been identified in patients with breast cancer; the role in colorectal cancer is more controversial. This chapter discusses the balance between carcinogen activation and detoxification...

  13. Study on IL-2 and CA 15-3 level as combined biomarkers in monitoring chemotherapeutic response among invasive breast cancer patients

    Science.gov (United States)

    Hameed, Ahmed Muthanna Abdul; Hamid, Auni Fatin Abdul; Shahfiza Noor, Nurul; Appalanaido, Gokula Kumar; Bariyah Sahul Hamid, Shahrul

    2017-05-01

    In Malaysia, breast cancer is the most frequent type of disease among women. This study was designed to determine the clinical usefulness of carbohydrate antigen (CA 15-3) and interleukin 2 (IL-2) levels as combined biomarkers in monitoring breast cancer patient’s response to chemotherapy. Ethical approval was obtained to recruit patients with histologically confirmed invasive ductal carcinoma (IDC) attending Oncology Clinic at Advanced Medical and Dental Institute. Whole blood was collected from 10 IDC breast cancer patients’ pre and post primary chemotherapy. Plasma was separated from the whole blood to determine the CA 15-3 level and IL-2 level using enzyme-linked immunosorbent assay (ELISA) pre and post-treatment. In addition, the histological findings, tumour stage and other patients’ data were obtained from the medical record. Findings showed that IL-2 had borderline significant changes between pre- and post-chemotherapy (p = 0.074) whereas for CA 15-3, there was insignificant differences of CA 15-3 level between pre and post-chemotherapy (p > 0.05). It was noted that only CA 15-3 level had significant correlation with tumour size. This study demonstrates that IL-2 level requires further investigation in a larger sample size to correlate its potential use as combined biomarker with CA 15-3 in monitoring response to chemotherapy.

  14. Statins and breast cancer prognosis

    DEFF Research Database (Denmark)

    Ahern, Thomas P; Lash, Timothy L; Damkier, Per

    2014-01-01

    Much preclinical and epidemiological evidence supports the anticancer effects of statins. Epidemiological evidence does not suggest an association between statin use and reduced incidence of breast cancer, but does support a protective effect of statins-especially simvastatin-on breast cancer...... recurrence. Here, we argue that the existing evidence base is sufficient to justify a clinical trial of breast cancer adjuvant therapy with statins and we advocate for such a trial to be initiated without delay. If a protective effect of statins on breast cancer recurrence is supported by trial evidence......, then the indications for a safe, well tolerated, and inexpensive treatment can be expanded to improve outcomes for breast cancer survivors. We discuss several trial design opportunities-including candidate predictive biomarkers of statin safety and efficacy-and off er solutions to the key challenges involved...

  15. Loss of PTEN as a Predictive Biomarker of Response to Lithium Chloride, A Potential Targeted Treatment for Breast Cancer

    Science.gov (United States)

    2013-11-01

    oestrogen and epidermal growth factor receptors in human breast cancer. Br J Cancer 1994; 69:1032-7. 19. Klijn JG, Look MP, Portengen H, Alexieva-Figusch...microparticles in water -in-oil emulsions. Nat Methods 2006;3:551–9. 18. Diehl F, Schmidt K, Choti MA, Romans K, Goodman S, Li M, et al. Circulating mutant

  16. SIAH and EGFR, Two RAS Pathway Biomarkers, are Highly Prognostic in Locally Advanced and Metastatic Breast Cancer

    Directory of Open Access Journals (Sweden)

    Lauren L. Siewertsz van Reesema

    2016-09-01

    Funding: This work was supported by the Dorothy G. Hoefer Foundation for Breast Cancer Research (A.H. Tang; Center for Innovative Technology (CIT-Commonwealth Research Commercialization Fund (CRCF (MF14S-009-LS to A.H. Tang, and National Cancer Institute (CA140550 to A.H. Tang.

  17. Image Based Biomarker of Breast Cancer Risk: Analysis of Risk Disparity among Minority Populations

    Science.gov (United States)

    2013-03-01

    approximation for the boundary between Cooper’s ligaments and adi - pose tissue, as simulated in our software breast phantom [1], can be obtained as fol- lows...Health, Food and Drug Administration, Silver Spring, MD † Computer and Information Sciences Department, Delaware State University, Dover, DE

  18. Zinc isotopic compositions of breast cancer tissue.

    Science.gov (United States)

    Larner, Fiona; Woodley, Laura N; Shousha, Sami; Moyes, Ashley; Humphreys-Williams, Emma; Strekopytov, Stanislav; Halliday, Alex N; Rehkämper, Mark; Coombes, R Charles

    2015-01-01

    An early diagnostic biomarker for breast cancer is essential to improve outcome. High precision isotopic analysis, originating in Earth sciences, can detect very small shifts in metal pathways. For the first time, the natural intrinsic Zn isotopic compositions of various tissues in breast cancer patients and controls were determined. Breast cancer tumours were found to have a significantly lighter Zn isotopic composition than the blood, serum and healthy breast tissue in both groups. The Zn isotopic lightness in tumours suggests that sulphur rich metallothionein dominates the isotopic selectivity of a breast tissue cell, rather than Zn-specific proteins. This reveals a possible mechanism of Zn delivery to Zn-sequestering vesicles by metallothionein, and is supported by a similar signature observed in the copper isotopic compositions of one breast cancer patient. This change in intrinsic isotopic compositions due to cancer has the potential to provide a novel early biomarker for breast cancer.

  19. Treatment Option Overview (Breast Cancer)

    Science.gov (United States)

    ... of Breast & Gynecologic Cancers Breast Cancer Screening Research Breast Cancer Treatment (PDQ®)–Patient Version General Information About Breast Cancer Go to Health Professional Version Key Points Breast ...

  20. General Information about Breast Cancer

    Science.gov (United States)

    ... of Breast & Gynecologic Cancers Breast Cancer Screening Research Breast Cancer Treatment (PDQ®)–Patient Version General Information About Breast Cancer Go to Health Professional Version Key Points Breast ...

  1. Evidence for biological effects of metformin in operable breast cancer: biomarker analysis in a pre-operative window of opportunity randomized trial.

    Science.gov (United States)

    Hadad, Sirwan M; Coates, Philip; Jordan, Lee B; Dowling, Ryan J O; Chang, Martin C; Done, Susan J; Purdie, Colin A; Goodwin, Pamela J; Stambolic, Vuk; Moulder-Thompson, Stacy; Thompson, Alastair M

    2015-02-01

    Metformin has therapeutic potential against breast cancer, but the mechanisms of action in vivo remain uncertain. This study examined biomarker effects of metformin in primary breast cancer in a preoperative window of opportunity trial. Non-diabetic women with operable invasive breast cancer were randomized to receive open label pre-operative metformin (500 mg daily for 1 week then 1 g twice daily for a further week) or as controls, not receiving metformin. Patients in both arms had a core biopsy pre-randomisation and again at the time of surgery. Immunohistochemistry for phospho-AMPK (pAMPK), phospho-Akt (pAkt), insulin receptor, cleaved caspase-3, and Ki67 was performed on formalin-fixed paraffin-embedded cores, scored blinded to treatment and analysed by paired t test. In metformin-treated patients, significant up-regulation of pAMPK (paired t test, p = 0.04) and down-regulation of pAkt (paired t test, p = 0.043) were demonstrated compared to the control group. Insulin receptor and serum insulin remained similar following metformin treatment compared with a rise in insulin receptor and insulin in controls. Significant falls in Ki67 and cleaved caspase-3 (paired t test, p = 0.044) were seen in the metformin-treated patients but not in the control group. Changes were independent of body mass index. These biomarker data suggest mechanisms for metformin action in vivo in breast cancer patients via up-regulation of tumor pAMPK, down-regulation of pAkt, and suppression of insulin responses reflecting cytostatic rather than cytotoxic mechanisms.

  2. Molecular detection of peripheral blood breast cancer mRNA transcripts as a surrogate biomarker for circulating tumor cells.

    Directory of Open Access Journals (Sweden)

    Adriana Lasa

    Full Text Available Circulating tumor cells (CTCs are becoming a scientifically recognized indicator of primary tumors and/or metastasis. These cells can now be accurately detected and characterized as the result of technological advances. We analyzed the presence of CTCs in the peripheral blood of patients with metastatic breast cancer by real-time reverse-transcription PCR (RT-qPCR using a panel of selected genes. The analysis of a single marker, without an EpCAM based enrichment approach, allowed the positive identification of 35% of the metastatic breast cancer patients. The analysis of five genes (SCGB2, TFF1, TFF3, Muc1, KRT20 performed in all the samples increased the detection to 61%. We describe a sensitive, reproducible and easy to implement approach to characterize CTC in patients with metastasic breast cancer.

  3. Molecular detection of peripheral blood breast cancer mRNA transcripts as a surrogate biomarker for circulating tumor cells.

    Science.gov (United States)

    Lasa, Adriana; Garcia, Arnal; Alonso, Carmen; Millet, Pilar; Cornet, Mónica; Ramón y Cajal, Teresa; Baiget, Montserrat; Barnadas, Agusti

    2013-01-01

    Circulating tumor cells (CTCs) are becoming a scientifically recognized indicator of primary tumors and/or metastasis. These cells can now be accurately detected and characterized as the result of technological advances. We analyzed the presence of CTCs in the peripheral blood of patients with metastatic breast cancer by real-time reverse-transcription PCR (RT-qPCR) using a panel of selected genes. The analysis of a single marker, without an EpCAM based enrichment approach, allowed the positive identification of 35% of the metastatic breast cancer patients. The analysis of five genes (SCGB2, TFF1, TFF3, Muc1, KRT20) performed in all the samples increased the detection to 61%. We describe a sensitive, reproducible and easy to implement approach to characterize CTC in patients with metastasic breast cancer.

  4. Validation of New Cancer Biomarkers

    DEFF Research Database (Denmark)

    Duffy, Michael J; Sturgeon, Catherine M; Söletormos, Georg

    2015-01-01

    BACKGROUND: Biomarkers are playing increasingly important roles in the detection and management of patients with cancer. Despite an enormous number of publications on cancer biomarkers, few of these biomarkers are in widespread clinical use. CONTENT: In this review, we discuss the key steps in ad...

  5. Breast Cancer Disparities

    Science.gov (United States)

    ... 2.65 MB] Read the MMWR Science Clips Breast Cancer Black Women Have Higher Death Rates from Breast ... of Page U.S. State Info Number of Additional Breast Cancer Deaths Among Black Women, By State SOURCE: National ...

  6. Inflammatory Breast Cancer

    Science.gov (United States)

    ... breast cancer correctly. Their recommendations are summarized below. Minimum criteria for a diagnosis of inflammatory breast cancer ... Initial biopsy samples from the affected breast show invasive carcinoma. Further examination of tissue from the affected ...

  7. Breast cancer in men

    Science.gov (United States)

    ... in situ - male; Intraductal carcinoma - male; Inflammatory breast cancer - male; Paget disease of the nipple - male; Breast cancer - male ... The cause of breast cancer in men is not clear. But there are risk factors that make breast cancer more likely in men: Exposure to ...

  8. Serum Biomarkers for the Detection of Cardiac Toxicity after Chemotherapy and Radiation Therapy in Breast Cancer Patients

    Directory of Open Access Journals (Sweden)

    Sibo eTian

    2014-10-01

    Full Text Available Multi-modality cancer treatments that include chemotherapy, radiation therapy, and targeted agents are highly effective therapies. Their use, especially in combination, is limited by the risk of significant cardiac toxicity. The current paradigm for minimizing cardiac morbidity, based on serial cardiac function monitoring, is suboptimal. An alternative approach based on biomarker testing, has emerged as a promising adjunct and a potential substitute to routine echocardiography. Biomarkers, most prominently cardiac troponins and natriuretic peptides, have been evaluated for their ability to describe the risk of potential cardiac dysfunction in clinically asymptomatic patients. Early rises in cardiac troponin concentrations have consistently predicted the risk and severity of significant cardiac events in patients treated with anthracycline-based chemotherapy. Biomarkers represent a novel, efficient, and robust clinical decision tool for the management of cancer therapy-induced cardiotoxicity. This article aims to review the clinical evidence that supports the use of established biomarkers such as cardiac troponins and natriuretic peptides, as well as emerging data on proposed biomarkers.

  9. Imaging male breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Doyle, S., E-mail: sdoyle2@nhs.net [Primrose Breast Care Unit, Derriford Hospital, Plymouth (United Kingdom); Steel, J.; Porter, G. [Primrose Breast Care Unit, Derriford Hospital, Plymouth (United Kingdom)

    2011-11-15

    Male breast cancer is rare, with some pathological and radiological differences from female breast cancer. There is less familiarity with the imaging appearances of male breast cancer, due to its rarity and the more variable use of preoperative imaging. This review will illustrate the commonest imaging appearances of male breast cancer, with emphasis on differences from female breast cancer and potential pitfalls in diagnosis, based on a 10 year experience in our institution.

  10. Cancer Biomarkers | Division of Cancer Prevention

    Science.gov (United States)

    [[{"fid":"175","view_mode":"default","fields":{"format":"default","field_file_image_alt_text[und][0][value]":"Cancer Biomarkers Research Group Homepage Logo","field_file_image_title_text[und][0][value]":"Cancer Biomarkers Research Group Homepage Logo","field_folder[und]":"15"},"type":"media","attributes":{"alt":"Cancer Biomarkers Research Group Homepage Logo","title":"Cancer Biomarkers Research Group Homepage Logo","height":"266","width":"400","style":"width: 400px; height: 266px;","class":"i | Research to identify, develop and validate biomarkers for early cancer detection and risk assessment.

  11. CDK 4/6 inhibitor palbociclib (PD0332991) in Rb+ advanced breast cancer: phase II activity, safety, and predictive biomarker assessment.

    Science.gov (United States)

    DeMichele, Angela; Clark, Amy S; Tan, Kay See; Heitjan, Daniel F; Gramlich, Kristi; Gallagher, Maryann; Lal, Priti; Feldman, Michael; Zhang, Paul; Colameco, Christopher; Lewis, David; Langer, Melissa; Goodman, Noah; Domchek, Susan; Gogineni, Keerthi; Rosen, Mark; Fox, Kevin; O'Dwyer, Peter

    2015-03-01

    The G1-S checkpoint of the cell cycle is frequently dysregulated in breast cancer. Palbociclib (PD0332991) is an oral inhibitor of CDK4/6. Based upon preclinical/phase I activity, we performed a phase II, single-arm trial of palbociclib in advanced breast cancer. Eligible patients had histologically confirmed, metastatic breast cancer positive for retinoblastoma (Rb) protein and measureable disease. Palbociclib was given at 125 mg orally on days 1 to 21 of a 28-day cycle. Primary objectives were tumor response and tolerability. Secondary objectives included progression-free survival (PFS) and assessment of Rb expression/localization, KI-67, p16 loss, and CCND1 amplification. Thirty-seven patients were enrolled; 84% hormone-receptor (HR)(+)/Her2(-), 5% HR(+)/Her2(+), and 11% HR(-)/Her2(-), with a median of 2 prior cytotoxic regimens. Two patients had partial response (PR) and 5 had stable disease ≥ 6 months for a clinical benefit rate (CBR = PR + 6moSD) of 19% overall, 21% in HR(+), and 29% in HR(+)/Her2(-) who had progressed through ≥2 prior lines of hormonal therapy. Median PFS overall was 3.7 months [95% confidence interval (CI), 1.9-5.1], but significantly longer for those with HR(+) versus HR(-) disease (P = 0.03) and those who had previously progressed through endocrine therapy for advanced disease (P = 0.02). Grade 3/4 toxicities included neutropenia (51%), anemia (5%), and thrombocytopenia (22%). Twenty-four percent had treatment interruption and 51% had dose reduction, all for cytopenias. No biomarker identified a sensitive tumor population. Single-agent palbociclib is well tolerated and active in patients with endocrine-resistant, HR(+), Rb-positive breast cancer. Cytopenias were uncomplicated and easily managed with dose reduction. ©2014 American Association for Cancer Research.

  12. Design of the SHAPE-2 study: the effect of physical activity, in addition to weight loss, on biomarkers of postmenopausal breast cancer risk

    Science.gov (United States)

    2013-01-01

    Background Physical inactivity and overweight are two known risk factors for postmenopausal breast cancer. Former exercise intervention studies showed that physical activity influences sex hormone levels, known to be related to postmenopausal breast cancer, mainly when concordant loss of body weight was achieved. The question remains whether there is an additional beneficial effect of physical activity when weight loss is reached. The aim of this study is to investigate the effect attributable to exercise on postmenopausal breast cancer risk biomarkers, when equivalent weight loss is achieved compared with diet-induced weight loss. Design The SHAPE-2 study is a three-armed, multicentre trial. 243 sedentary, postmenopausal women who are overweight or obese (BMI 25–35 kg/m2) are enrolled. After a 4-6 week run-in period, wherein a baseline diet is prescribed, women are randomly allocated to (1) a diet group, (2) an exercise group or (3) a control group. The aim of both intervention groups is to lose an amount of 5–6 kg body weight in 10–14 weeks. The diet group follows an energy restricted diet and maintains the habitual physical activity level. The exercise group participates in a 16-week endurance and strength training programme of 4 hours per week. Furthermore, they are prescribed a moderate caloric restriction. The control group is asked to maintain body weight and continue the run-in baseline diet. Measurements include blood sampling, questionnaires, anthropometrics (weight, height, waist and hip circumference), maximal cycle exercise test (VO2peak), DEXA-scan (body composition) and abdominal MRI (subcutaneous and visceral fat). Primary outcomes are serum levels of oestradiol, oestrone, testosterone and sex hormone binding globulin (SHBG). Discussion This study will give insight in the potential attributable effect of physical activity on breast cancer risk biomarkers and whether this effect is mediated by changes in body composition, in postmenopausal

  13. Effect of a low fat versus a low carbohydrate weight loss dietary intervention on biomarkers of long term survival in breast cancer patients ('CHOICE': study protocol

    Directory of Open Access Journals (Sweden)

    Daeninck Elizabeth A

    2011-07-01

    Full Text Available Abstract Background Weight loss in overweight or obese breast cancer patients is associated with an improved prognosis for long term survival. However, it is not clear whether the macronutrient composition of the chosen weight loss dietary plan imparts further prognostic benefit. A study protocol is presented for a dietary intervention to investigate the effects of weight loss dietary patterns that vary markedly in fat and carbohydrate contents on biomarkers of exposure to metabolic processes that may promote tumorigenesis and that are predictive of long term survival. The study will also determine how much weight must be lost for biomarkers to change in a favorable direction. Methods/Design Approximately 370 overweight or obese postmenopausal breast cancer survivors (body mass index: 25.0 to 34.9 kg/m2 will be accrued and assigned to one of two weight loss intervention programs or a non-intervention control group. The dietary intervention is implemented in a free living population to test the two extremes of popular weight loss dietary patterns: a high carbohydrate, low fat diet versus a low carbohydrate, high fat diet. The effects of these dietary patterns on biomarkers for glucose homeostasis, chronic inflammation, cellular oxidation, and steroid sex hormone metabolism will be measured. Participants will attend 3 screening and dietary education visits, and 7 monthly one-on-one dietary counseling and clinical data measurement visits in addition to 5 group visits in the intervention arms. Participants in the control arm will attend two clinical data measurement visits at baseline and 6 months. The primary outcome is high sensitivity C-reactive protein. Secondary outcomes include interleukin-6, tumor necrosis factor-α, insulin-like growth factor-1 (IGF, IGF binding protein-3, 8-isoprostane-F2-alpha, estrone, estradiol, progesterone, sex hormone binding globulin, adiponectin, and leptin. Discussion While clinical data indicate that excess weight

  14. A Novel Imaging Biomarker Extracted from Fluorescence Microscopic Imaging of TRA-8/DR5 Oligomers Predicts TRA-8 Therapeutic Efficacy in Breast and Pancreatic Cancer Mouse Models.

    Science.gov (United States)

    Kim, Harrison; Buchsbaum, Donald J; Zinn, Kurt R

    2016-06-01

    The aim of the study was to develop a reliable quantitative imaging biomarker from fluorescence microscopic imaging of TRA-8/death receptor 5 (DR5) oligomer to predict TRA-8 therapeutic efficacy in human breast and pancreatic cancer mouse models. Two breast (2LMP, SUM159) and two pancreatic (MIA PaCa-2, PANC1) cancer cell lines were used. 10(5) cells per cell line were placed in a culture dish and treated with Cy5.5-labeled TRA-8 overnight in vitro. Three fluorescence microphotographs (×20) were acquired from randomly selected areas, and about 300 cells were analyzed per cell line. Two-dimensional (2D) fluorescence signal distribution of Cy5.5-TRA-8 on each cell was measured. Gaussian curve fitting to the distribution was determined by the least square regression method, and the coefficient of determination (R (2)) of the fitting was found. In addition, two features of the best fitting Gaussian curve such as peak amplitude and the volume under the curve (VUC) were retrieved. A novel image biomarker was extracted by correlating the combination of R (2) value, peak amplitude, and the VUC with the logarithmic values of the half maximal inhibitory concentrations (IC50) of TRA-8 for the four cell lines or the percentage of tumor growth inhibition (%TGI) at a week of TRA-8 treatment in animal models. Cy5.5-TRA-8 binding to DR5 receptors resulted in an oligomer on each cell membrane, and its fluorescence signal distribution followed Gaussian curve. Peak amplitude of fluorescence signal in the oligomeric region, R (2) value of the Gaussian fitting, and the VUC in TRA-8-sensitive cells were significantly higher than those in resistant cells (p TRA-8 may serve as a predictive biomarker of TRA-8 therapy for cancer patients.

  15. Breast Cancer Metastasis

    Science.gov (United States)

    Marino, Natascia; Woditschka, Stephan; Reed, L. Tiffany; Nakayama, Joji; Mayer, Musa; Wetzel, Maria; Steeg, Patricia S.

    2014-01-01

    Despite important progress in adjuvant and neoadjuvant therapies, metastatic disease often develops in breast cancer patients and remains the leading cause of their deaths. For patients with established metastatic disease, therapy is palliative, with few breaks and with mounting adverse effects. Many have hypothesized that a personalized or precision approach (the terms are used interchangeably) to cancer therapy, in which treatment is based on the individual characteristics of each patient, will provide better outcomes. Here, we discuss the molecular basis of breast cancer metastasis and the challenges in personalization of treatment. The instability of metastatic tumors remains a leading obstacle to personalization, because information from a patient’s primary tumor may not accurately reflect the metastasis, and one metastasis may vary from another. Furthermore, the variable presence of tumor subpopulations, such as stem cells and dormant cells, may increase the complexity of the targeted treatments needed. Although molecular signatures and circulating biomarkers have been identified in breast cancer, there is lack of validated predictive molecular markers to optimize treatment choices for either prevention or treatment of metastatic disease. Finally, to maximize the information that can be obtained, increased attention to clinical trial design in the metastasis preventive setting is needed. PMID:23895915

  16. Applicability of HIN-1, MGMT and RASSF1A promoter methylation as biomarkers for detecting field cancerization in breast cancer

    National Research Council Canada - National Science Library

    Spitzwieser, Melanie; Holzweber, Elisabeth; Pfeiler, Georg; Hacker, Stefan; Cichna-Markl, Margit

    2015-01-01

    .... This phenomenon is metaphorically called field cancerization or field defect. Field cancerization is regarded as clinically significant because it is assumed to be an important factor in local recurrence of cancer...

  17. Stages of Male Breast Cancer

    Science.gov (United States)

    ... Breast & Gynecologic Cancers Breast Cancer Screening Research Male Breast Cancer Treatment (PDQ®)–Patient Version General Information about Male Breast Cancer Go to Health Professional Version Key Points Male ...

  18. Design of the SHAPE-2 study: the effect of physical activity, in addition to weight loss, on biomarkers of postmenopausal breast cancer risk

    NARCIS (Netherlands)

    van Gemert, W.A.; Iestra, J.I.; Schuit, A.J.; May, A.M.; Takken, T.; Veldhuis, W.B.; van der Palen, J.; Wittink, H.; Peeters, P.H.; Monnikhof, E.M.

    2013-01-01

    Background: Physical inactivity and overweight are two known risk factors for postmenopausal breast cancer. Former exercise intervention studies showed that physical activity influences sex hormone levels, known to be related to postmenopausal breast cancer, mainly when concordant loss of body

  19. Expression of Biomarkers CXCR4, IL11-RA, TFF1, MLF1P in Advanced Breast Cancer Patients with Bone Metastatic: a Diagnostic Study

    Directory of Open Access Journals (Sweden)

    Cosphiadi Irawan

    2017-02-01

    Full Text Available Aim: to analyze expression of biomarkers CXCR4, IL11-RA, TFF1 and MLF1P, and clinicopathology in advanced breast cancer patients with bone metastatic. Methods: this is a cross-sectional study. Analysis was done against a total of 92 breast cancer patients, including 46 bone metastatic patients and 46 non-bone metastatic patients. Immunohistochemistry and microarray analysis was performed in 81 formalin fixed paraffin embedded (FFPE samples from 81 patients were used. Data were collected through medical records, immunohistochemistry (IHC, and microarray with nanoString nCounterTM. Results: this article is part one of a two stage reporting research results. In part one we got the results of the IHC analysis, IL11-RA with cut-off ≥103.5 showed OR 3.803 (95 % confidence interval [CI], 1.375-10.581, p=0.010, MLF1P with cut-off ≥83.0 OR 2.784 (95% CI, 1.009-7.681, p=0.048, and ER+ OR 7.640 (95 % CI, 2.599-22.459, p<0.000, were associated with bone metastastic incidences in advanced breast cancer, and were statistically significantly different. A combination of IL-11RA, MLF1P and ER+, showed an accuracy of approaching 80% to discriminate between bone metastatic and non bone metastatic in advanced breast cancer patients. Conclusion: IL11-RA, MLF1P, and ER+ were the determinants that were associated with increasing bone metastasis incidence.

  20. Biomarker signatures of mitochondrial NDUFS3 in invasive breast carcinoma.

    Science.gov (United States)

    Suhane, Sonal; Berel, Dror; Ramanujan, V Krishnan

    2011-09-09

    We present evidence for potential biomarker utility of a mitochondrial complex I subunit, (NDUFS3) in discriminating normal and highly invasive breast carcinoma specimens obtained from clinical patients. Besides being a robust indicator of breast cancer aggressiveness, NDUFS3 also shows clear signatures of a hypoxia/necrosis marker in invasive ductal carcinoma specimens. Statistically significant positive correlation was observed between nuclear grade and NDUFS3 expression level in the tumor specimens analyzed. We support these findings with a plausible mechanism involving mitochondrial complex I assembly defects and/or redox buffering induced mitochondrial dysfunction during the process of cancer cell transformation. From a clinical standpoint, this novel observation adds value in augmenting the current receptor-based biomarkers for better accuracy in diagnosis and predicting survival rate in patients with breast carcinoma. Copyright © 2011 Elsevier Inc. All rights reserved.

  1. Family History of Breast Cancer, Breast Density, and Breast Cancer Risk in a U.S. Breast Cancer Screening Population.

    Science.gov (United States)

    Ahern, Thomas P; Sprague, Brian L; Bissell, Michael C S; Miglioretti, Diana L; Buist, Diana S M; Braithwaite, Dejana; Kerlikowske, Karla

    2017-06-01

    Background: The utility of incorporating detailed family history into breast cancer risk prediction hinges on its independent contribution to breast cancer risk. We evaluated associations between detailed family history and breast cancer risk while accounting for breast density.Methods: We followed 222,019 participants ages 35 to 74 in the Breast Cancer Surveillance Consortium, of whom 2,456 developed invasive breast cancer. We calculated standardized breast cancer risks within joint strata of breast density and simple (1st-degree female relative) or detailed (first-degree, second-degree, or first- and second-degree female relative) breast cancer family history. We fit log-binomial models to estimate age-specific breast cancer associations for simple and detailed family history, accounting for breast density.Results: Simple first-degree family history was associated with increased breast cancer risk compared with no first-degree history [Risk ratio (RR), 1.5; 95% confidence interval (CI), 1.0-2.1 at age 40; RR, 1.5; 95% CI, 1.3-1.7 at age 50; RR, 1.4; 95% CI, 1.2-1.6 at age 60; RR, 1.3; 95% CI, 1.1-1.5 at age 70). Breast cancer associations with detailed family history were strongest for women with first- and second-degree family history compared with no history (RR, 1.9; 95% CI, 1.1-3.2 at age 40); this association weakened in higher age groups (RR, 1.2; 95% CI, 0.88-1.5 at age 70). Associations did not change substantially when adjusted for breast density.Conclusions: Even with adjustment for breast density, a history of breast cancer in both first- and second-degree relatives is more strongly associated with breast cancer than simple first-degree family history.Impact: Future efforts to improve breast cancer risk prediction models should evaluate detailed family history as a risk factor. Cancer Epidemiol Biomarkers Prev; 26(6); 938-44. ©2017 AACR. ©2017 American Association for Cancer Research.

  2. Methylated genes as new cancer biomarkers.

    LENUS (Irish Health Repository)

    Duffy, M J

    2012-02-01

    Aberrant hypermethylation of promoter regions in specific genes is a key event in the formation and progression of cancer. In at least some situations, these aberrant alterations occur early in the formation of malignancy and appear to be tumour specific. Multiple reports have suggested that measurement of the methylation status of the promoter regions of specific genes can aid early detection of cancer, determine prognosis and predict therapy responses. Promising DNA methylation biomarkers include the use of methylated GSTP1 for aiding the early diagnosis of prostate cancer, methylated PITX2 for predicting outcome in lymph node-negative breast cancer patients and methylated MGMT in predicting benefit from alkylating agents in patients with glioblastomas. However, prior to clinical utilisation, these findings require validation in prospective clinical studies. Furthermore, assays for measuring gene methylation need to be standardised, simplified and evaluated in external quality assurance programmes. It is concluded that methylated genes have the potential to provide a new generation of cancer biomarkers.

  3. Beating Breast Cancer

    Science.gov (United States)

    ... of this page please turn JavaScript on. Feature: Breast Cancer Beating Breast Cancer Past Issues / Winter 2017 Table of Contents Melanie ... Her mother had died at age 49 of breast cancer after three battles with the disease. Ovarian cancer ...

  4. Tamoxifen for Breast Cancer

    Directory of Open Access Journals (Sweden)

    A Karn

    2010-03-01

    Full Text Available Breast cancer is one of the common cancers. Hormonal therapy along with surgery, chemotherapy, radiotherapy and targeted therapy are vital modalities for the management of breast cancer. Tamoxifen has been the most widely used hormonal therapy for more than two decades. In this article we review the benefits, dose, duration and timing of Tamoxifen therapy in patients with breast cancer. Keywords: breast cancer, hormonal therapy, tamoxifen.

  5. Molecular Detection of Peripheral Blood Breast Cancer mRNA Transcripts as a Surrogate Biomarker for Circulating Tumor Cells

    OpenAIRE

    Adriana Lasa; Arnal Garcia; Carmen Alonso; Pilar Millet; Mónica Cornet; Cajal, Teresa Ramón y; Montserrat Baiget; Agusti Barnadas

    2013-01-01

    Circulating tumor cells (CTCs) are becoming a scientifically recognized indicator of primary tumors and/or metastasis. These cells can now be accurately detected and characterized as the result of technological advances. We analyzed the presence of CTCs in the peripheral blood of patients with metastatic breast cancer by real-time reverse-transcription PCR (RT-qPCR) using a panel of selected genes. The analysis of a single marker, without an EpCAM based enrichment approach, allowed the positi...

  6. Green Tea Improves Metabolic Biomarkers, not Weight or Body Composition: A Pilot Study in Overweight Breast Cancer Survivors

    Science.gov (United States)

    Stendell-Hollis, Nicole R; Thomson, Cynthia A; Thompson, Patricia A; Bea, Jennifer W; Cussler, Ellen C; Hakim, Iman A

    2010-01-01

    Background Overweight status after breast cancer treatment may increase a woman’s risk for recurrent disease and/or early onset cardiovascular disease. Green tea has been proposed to promote weight loss and favourably modify glucose, insulin and blood lipids. This pilot study tested the effect of daily decaffeinated green tea consumption for 6 months on weight and body composition, select metabolic parameters, and lipid profiles in overweight breast cancer survivors. Methods The effect of daily decaffeinated green tea intake on weight, body composition and changes in resting metabolic rate, energy intake, glucose, insulin, HOMA-IR, and lipids was evaluated in overweight breast cancer survivors. Participants had a mean weight of 80.2 kg; BMI 30.1 kg/m2; and body fat 46.4%. Participants (N=54) were randomised to 960 mL decaffeinated green or placebo tea daily for 6 months. Results Average tea intake among study completers (N=39) was 5952 ± 1176 mL/week and was associated with a significant reduction in energy intake (P =0.02). Change in body weight of −1.2 kg (green tea) versus + 0.2 kg (placebo) suggests a weight change effect, but was not statistically significant. Decaffeinated green tea intake was associated with elevated HDL levels (P=0.003) and non-significant improvements in the HOMA-IR (−1.1±5.9: green tea; +3.2±7.2: herbal) and the HDL/LDL ratio. Conclusions Intake of decaffeinated green tea for 6 months was associated with a slight reduction in body weight and improved HDL and glucose homeostasis in overweight breast cancer survivors. PMID:20807303

  7. Circulating microRNAs in breast cancer

    DEFF Research Database (Denmark)

    Hamam, Rimi; Hamam, Dana; Alsaleh, Khalid A.

    2017-01-01

    Effective management of breast cancer depends on early diagnosis and proper monitoring of patients' response to therapy. However, these goals are difficult to achieve because of the lack of sensitive and specific biomarkers for early detection and for disease monitoring. Accumulating evidence...... in the past several years has highlighted the potential use of peripheral blood circulating nucleic acids such as DNA, mRNA and micro (mi)RNA in breast cancer diagnosis, prognosis and for monitoring response to anticancer therapy. Among these, circulating miRNA is increasingly recognized as a promising...... circulating miRNAs as diagnostic, prognostic or predictive biomarkers in breast cancer management....

  8. Early Detection of Breast Cancer Using Molecular Beacons

    National Research Council Canada - National Science Library

    Yang, Lily

    2008-01-01

    .... We proposed to use molecular beacon technology to detect the level of expression of several biomarker genes that are highly expressed in breast cancer cells but not in normal breast epithelial cells...

  9. GATA3 and TRPS1 are distinct biomarkers and prognostic factors in breast cancer: database mining for GATA family members in malignancies.

    Science.gov (United States)

    Lin, Hao-Yu; Zeng, De; Liang, Yuan-Ke; Wei, Xiao-Long; Chen, Chun-Fa

    2017-05-23

    GATA transcription factors are zinc finger DNA binding proteins that activate transcription during development and cell differentiation. To date, 7 members of GATA family have been reported. However, the expression patterns and the exact roles of distinct GATA family members contributing to tumorigenesis and progression of breast cancer (BC) remain to be elucidated. Here, we studied the expression of GATA transcripts in a variety of tumor types compared with the normal controls using the ONCOMINE and GOBO databases, along with their corresponding expression profiles in an array of cancer cell lines through CCLE analysis. Based on Kaplan-Meier plotter, we further investigated the prognostic values of GATA members specifically high expressed in BC patients. It was found that, when compared with normal tissues, GATA3 and TRPS1 were distinctly high expressed in BC patients among all GATA members. GATA3 expression was significantly associated with ESR1, while TRPS1 was correlated with ERBB2. In survival analysis, GATA3 and TRPS1 mRNA high expressions were correlated to better survival in BC patients, and TRPS1 high expression was significantly associated with longer RFS in patients who have received chemotherapy. These results suggest that GATA3 and TRPS1 are distinct biomarkers and essential prognostic factors for breast cancer.

  10. Breast cancer staging

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000911.htm Breast cancer staging To use the sharing features on this ... Once your health care team knows you have breast cancer , they will do more tests to stage it. ...

  11. HEREDITARY BREAST CANCER

    Directory of Open Access Journals (Sweden)

    E. M. Bit-Sava

    2013-01-01

    Full Text Available Hereditary breast cancer occurs in 5–20 % of cases and it is associated with inherited mutations in particular genes, such as BRCA1 и BRCA2 in most cases. The CHEK2, PTEN, TP53, ATM, RAD51, BLM, PALB2, Nbs genes are associated with low and median risks ofdeveloping breast cancer. Molecular genetic studies identify germinal mutations underlying hereditary breast cancer. In most cases hereditary breast cancer refers to triple-negative phenotype, which is the most aggressive type of breast cancer, that does not express the genes for estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 (HER2. The review presents the diagnostic and treatment methods of hereditary breast cancer. Clinical-morphological aspects allow the new diagnostic and treatment methods of hereditary breast cancer to be identified. Poly (ADP-ribose polymerase (PARP inhibitors demonstrate the potential for effective treatment of BRCA-associated breast cancer.

  12. Breast Cancer and Infertility

    Directory of Open Access Journals (Sweden)

    Guluzar Arzu Turan

    2015-09-01

    Full Text Available Breast cancer is the most common malignancy among women and may accompany infertility. The relationship between infertility treatment and breast cancer has not yet been proven. However, estrogen exposure is well known to cause breast cancer. Recent advances in treatment options have provided young patients with breast cancer a chance of being mother [Archives Medical Review Journal 2015; 24(3.000: 317-323

  13. Breast Cancer (For Kids)

    Science.gov (United States)

    ... Staying Safe Videos for Educators Search English Español Breast Cancer KidsHealth / For Kids / Breast Cancer What's in this ... for it when they are older. What Is Breast Cancer? The human body is made of tiny building ...

  14. Tumor Heterogeneity in Breast Cancer

    Science.gov (United States)

    Turashvili, Gulisa; Brogi, Edi

    2017-01-01

    Breast cancer is a heterogeneous disease and differs greatly among different patients (intertumor heterogeneity) and even within each individual tumor (intratumor heterogeneity). Clinical and morphologic intertumor heterogeneity is reflected by staging systems and histopathologic classification of breast cancer. Heterogeneity in the expression of established prognostic and predictive biomarkers, hormone receptors, and human epidermal growth factor receptor 2 oncoprotein is the basis for targeted treatment. Molecular classifications are indicators of genetic tumor heterogeneity, which is probed with multigene assays and can lead to improved stratification into low- and high-risk groups for personalized therapy. Intratumor heterogeneity occurs at the morphologic, genomic, transcriptomic, and proteomic levels, creating diagnostic and therapeutic challenges. Understanding the molecular and cellular mechanisms of tumor heterogeneity that are relevant to the development of treatment resistance is a major area of research. Despite the improved knowledge of the complex genetic and phenotypic features underpinning tumor heterogeneity, there has been only limited advancement in diagnostic, prognostic, or predictive strategies for breast cancer. The current guidelines for reporting of biomarkers aim to maximize patient eligibility for targeted therapy, but do not take into account intratumor heterogeneity. The molecular classification of breast cancer is not implemented in routine clinical practice. Additional studies and in-depth analysis are required to understand the clinical significance of rapidly accumulating data. This review highlights inter- and intratumor heterogeneity of breast carcinoma with special emphasis on pathologic findings, and provides insights into the clinical significance of molecular and cellular mechanisms of heterogeneity. PMID:29276709

  15. Screening for Breast Cancer.

    Science.gov (United States)

    Niell, Bethany L; Freer, Phoebe E; Weinfurtner, Robert Jared; Arleo, Elizabeth Kagan; Drukteinis, Jennifer S

    2017-11-01

    The goal of screening is to detect breast cancers when still curable to decrease breast cancer-specific mortality. Breast cancer screening in the United States is routinely performed with mammography, supplemental digital breast tomosynthesis, ultrasound, and/or MR imaging. This article aims to review the most commonly used breast imaging modalities for screening, discuss how often and when to begin screening with specific imaging modalities, and examine the pros and cons of screening. By the article's end, the reader will be better equipped to have informed discussions with patients and medical professionals regarding the benefits and disadvantages of breast cancer screening. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Breast asymmetry and predisposition to breast cancer

    OpenAIRE

    Scutt, D; Lancaster, GA; Manning, JT

    2006-01-01

    INTRODUCTION: It has been shown in our previous work that breast asymmetry is related to several of the known risk factors for breast cancer, and that patients with diagnosed breast cancer have more breast volume asymmetry, as measured from mammograms, than age-matched healthy women. METHODS: In the present study, we compared the breast asymmetry of women who were free of breast disease at time of mammography, but who had subsequently developed breast cancer, with that of age-matched healthy ...

  17. N-Terminal Pro-B-Type Natriuretic Peptide Plasma Levels as a Potential Biomarker for Cardiac Damage After Radiotherapy in Patients With Left-Sided Breast Cancer

    Energy Technology Data Exchange (ETDEWEB)

    D' Errico, Maria P., E-mail: patderrico@libero.it [Department of Laboratory Medicine, ' A. Perrino' Hospital, Brindisi (Italy); Grimaldi, Luca [Department of Medical Physics, ' A. Perrino' Hospital, Brindisi (Italy); Petruzzelli, Maria F. [Department of Radiation Oncology, ' A. Perrino' Hospital, Brindisi (Italy); Gianicolo, Emilio A.L. [Clinical Physiology Institute, National Research Council (IFC-CNR), Pisa-Lecce (Italy); Tramacere, Francesco [Department of Radiation Oncology, ' A. Perrino' Hospital, Brindisi (Italy); Monetti, Antonio; Placella, Roberto [Department of Laboratory Medicine, ' A. Perrino' Hospital, Brindisi (Italy); Pili, Giorgio [Department of Medical Physics, ' A. Perrino' Hospital, Brindisi (Italy); Andreassi, Maria Grazia; Sicari, Rosa; Picano, Eugenio [Clinical Physiology Institute, National Research Council (IFC-CNR), Pisa-Lecce (Italy); Portaluri, Maurizio [Department of Radiation Oncology, ' A. Perrino' Hospital, Brindisi (Italy); Clinical Physiology Institute, National Research Council (IFC-CNR), Pisa-Lecce (Italy)

    2012-02-01

    Purpose: Adjuvant radiotherapy (RT) after breast-conserving surgery has been associated with increased cardiovascular mortality. Cardiac biomarkers may aid in identifying patients with radiation-mediated cardiac dysfunction. We evaluated the correlation between N-terminal pro-B-type natriuretic peptide (NT-proBNP) and troponin (TnI) and the dose of radiation to the heart in patients with left-sided breast cancer. Methods and Materials: NT-proBNP and TnI plasma concentrations were measured in 30 left-sided breast cancer patients (median age, 55.0 years) 5 to 22 months after RT (Group I) and in 30 left-sided breast cancer patients (median age, 57.0 years) before RT as control group (Group II). Dosimetric and geometric parameters of heart and left ventricle were determined in all patients of Group I. Seventeen patients underwent complete two-dimensional echocardiography. Results: NT-proBNP levels were significantly higher (p = 0.03) in Group I (median, 90.0 pg/ml; range, 16.7-333.1 pg/ml) than in Group II (median, 63.2 pg/ml; range, 11.0-172.5 pg/ml). TnI levels remained below the cutoff threshold of 0.07 ng/ml in both groups. In patients with NT-proBNP values above the upper limit of 125 pg/ml, there were significant correlations between plasma levels and V{sub 3Gy}(%) (p = 0.001), the ratios D{sub 15cm{sup 3}}(Gy)/D{sub mean}(Gy) (p = 0.01), the ratios D{sub 15cm}{sup 3}/D{sub 50%} (Gy) (p = 0.008) for the heart and correlations between plasma levels and V{sub 2Gy} (%) (p = 0.002), the ratios D{sub 1cm{sup 3}}(Gy)/D{sub mean}(Gy) (p = 0.03), and the ratios D{sub 0.5cm{sup 3}}(Gy)/D{sub 50%}(Gy) (p = 0.05) for the ventricle. Conclusions: Patients with left-sided breast cancer show higher values of NT-pro BNP after RT when compared with non-RT-treated matched patients, increasing in correlation with high doses in small volumes of heart and ventricle. The findings of this study show that the most important parameters are not the mean doses but instead the small

  18. A comparison of bone-related biomarkers and CA27.29 to assess response to treatment of osseous metastatic breast cancer.

    Science.gov (United States)

    Lüfter, D; Richter, A; Günther, S; Flath, B; Akrivakis, C; Geppert, R; Wernecke, K D; Possinger, K

    2000-01-01

    The assessment of bone metastases by clinical examination or imaging techniques is still considered unreliable. We compared a specific marker of bone resorption, urinary deoxypyridinoline (DPD)-crosslinks, with serum calcium (Ca), alkaline phosphatase (AP) and CA27.29, to evaluate the status of bone metastases in patients with breast cancer. Second morning voided urine was collected from 2 groups of patient (pts), those without evidence of disease (n = 118), and those with bone metastases (n = 85) under specific therapy plus pamidronate. DPD and CA27.29 were measured on the automated ACS180 system (Bayer Diagnostics, Tarrytown, NY, USA). Receiver operating characteristics (ROC) curves were established for each of the 4 biomarkers to determine whether they could distinguish the 2 subsets of pts with clinically sufficient validity, and to establish the corresponding cut-off values. Neither Ca nor AP was useful in discriminating the 2 subgroups. At a DPD cut-off of 13 nmol/mmol, we found a specificity of 69% and a sensitivity of 53% for diagnosing bone metastases. Best results, however, were seen for CA27.29. A cut-off value of 30 U/ml resulted in a specificity of 62% and a sensitivity of 81%. CA27.29 was the best parameter for the discrimination of stage IV breast cancer with bone metastases. The primary advantage of DPD lies in the monitoring of bone metastases under specific therapy.

  19. Biomarker signatures of mitochondrial NDUFS3 in invasive breast carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Suhane, Sonal [Metabolic Photonics Laboratory, Departments of Surgery and Biomedical Sciences, Cedars-Sinai Medical Center, 8700 Beverly Blvd., Los Angeles, CA 90048 (United States); Berel, Dror [Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, 8700 Beverly Blvd., Los Angeles, CA 90048 (United States); Ramanujan, V. Krishnan, E-mail: Ramanujanv@csmc.edu [Metabolic Photonics Laboratory, Departments of Surgery and Biomedical Sciences, Cedars-Sinai Medical Center, 8700 Beverly Blvd., Los Angeles, CA 90048 (United States)

    2011-09-09

    Highlights: {yields} We monitored mitochondrial NDUFS3 expression in clinical breast cancer specimens. {yields} NDUFS3 expression is significantly higher in highly invasive cancer specimens. {yields} Increased NDUFS3 expression correlates with tumor nuclear grade. {yields} NDUFS3 expression in invasive ductal carcinoma is a potential hypoxia marker. -- Abstract: We present evidence for potential biomarker utility of a mitochondrial complex I subunit, (NDUFS3) in discriminating normal and highly invasive breast carcinoma specimens obtained from clinical patients. Besides being a robust indicator of breast cancer aggressiveness, NDUFS3 also shows clear signatures of a hypoxia/necrosis marker in invasive ductal carcinoma specimens. Statistically significant positive correlation was observed between nuclear grade and NDUFS3 expression level in the tumor specimens analyzed. We support these findings with a plausible mechanism involving mitochondrial complex I assembly defects and/or redox buffering induced mitochondrial dysfunction during the process of cancer cell transformation. From a clinical standpoint, this novel observation adds value in augmenting the current receptor-based biomarkers for better accuracy in diagnosis and predicting survival rate in patients with breast carcinoma.

  20. Breast Cancer Rates by State

    Science.gov (United States)

    ... Associated Lung Ovarian Prostate Skin Uterine Cancer Home Breast Cancer Rates by State Language: English (US) Español (Spanish) ... from breast cancer each year. Rates of Getting Breast Cancer by State The number of people who get ...

  1. Heterogeneous DNA Methylation Patterns in the GSTP1 Promoter Lead to Discordant Results between Assay Technologies and Impede Its Implementation as Epigenetic Biomarkers in Breast Cancer

    Directory of Open Access Journals (Sweden)

    Grethe I. Grenaker Alnaes

    2015-09-01

    Full Text Available Altered DNA methylation patterns are found in many diseases, particularly in cancer, where the analysis of DNA methylation holds the promise to provide diagnostic, prognostic and predictive information of great clinical value. Methylation of the promoter-associated CpG island of GSTP1 occurs in many hormone-sensitive cancers, has been shown to be a biomarker for the early detection of cancerous lesions and has been associated with important clinical parameters, such as survival and response to treatment. In the current manuscript, we assessed the performance of several widely-used sodium bisulfite conversion-dependent methods (methylation-specific PCR, MethyLight, pyrosequencing and MALDI mass-spectrometry for the analysis of DNA methylation patterns in the GSTP1 promoter. We observed large discordances between the results obtained by the different technologies. Cloning and sequencing of the investigated region resolved single-molecule DNA methylation patterns and identified heterogeneous DNA methylation patterns as the underlying cause of the differences. Heterogeneous DNA methylation patterns in the GSTP1 promoter constitute a major obstacle to the implementation of DNA methylation-based analysis of GSTP1 and might explain some of the contradictory findings in the analysis of the significance of GSTP1 promoter methylation in breast cancer.

  2. Multicellular Tumour Spheroid as a model for evaluation of [18F]FDG as biomarker for breast cancer treatment monitoring

    Directory of Open Access Journals (Sweden)

    Josephsson Raymond

    2006-03-01

    Full Text Available Abstract Background In order to explore a pre-clinical method to evaluate if [18F]FDG is valid for monitoring early response, we investigated the uptake of FDG in Multicellular tumour spheroids (MTS without and with treatment with five routinely used chemotherapy agents in breast cancer. Methods The response to each anticancer treatment was evaluated by measurement of the [18F]FDG uptake and viable volume of the MTSs after 2 and 3 days of treatment. Results The effect of Paclitaxel and Docetaxel on [18F]FDG uptake per viable volume was more evident in BT474 (up to 55% decrease than in MCF-7 (up to 25% decrease. Doxorubicin reduced the [18F]FDG uptake per viable volume more noticeable in MCF-7 (25% than in BT474 MTSs. Tamoxifen reduced the [18F]FDG uptake per viable volume only in MCF-7 at the highest dose of 1 μM. No effect of Imatinib was observed. Conclusion MTS was shown to be appropriate to investigate the potential of FDG-PET for early breast cancer treatment monitoring; the treatment effect can be observed before any tumour size changes occur. The combination of PET radiotracers and image analysis in MTS provides a good model to evaluate the relationship between tumour volume and the uptake of metabolic tracer before and after chemotherapy. This feature could be used for screening and selecting PET-tracers for early assessment of treatment response. In addition, this new method gives a possibility to assess quickly, and in vitro, a good preclinical profile of existing and newly developed anti-cancer drugs.

  3. breast cancer screening in

    African Journals Online (AJOL)

    Is Breast transillumination a viable option for breast cancer screening in limited resource settings? Authors: Elobu EA M.Med, Galukande M M M.Med, MSc, FCS, Namuguzi D M.Med, Muyinda Z M.Med. Affiliations: breast cancer screening in limited resource settings? Authors: Elobu EA1 M.Med, Galukande M1 M M.Med, ...

  4. Metaplastic Breast Cancer

    OpenAIRE

    T?rkan, Halil; G?kg?z, M. ?ehsuvar; Parlak, N. Serhat

    2016-01-01

    Metaplastic Breast Cancer (MBC) is a term referring to a heterogeneous group with malignant epithelial and mesenchymal tissue components. MBC is a rare disease, accounting for 0.2% of all breast cancers. Most MBC are triple negative cancers with poor prognosis and an aggressive clinical course. Herein, we aimed to present a 74-year-old patient with metaplastic breast cancer along with clinical, radiologic and pathologic properties.

  5. Breast Cancer Risk in American Women

    Science.gov (United States)

    ... of Breast & Gynecologic Cancers Breast Cancer Screening Research Breast Cancer Risk in American Women On This Page What ... risk of developing the disease. Personal history of breast cancer : Women who have had breast cancer are more ...

  6. [Breast cancer surgery].

    Science.gov (United States)

    Vlastos, Georges; Berclaz, Gilles; Langer, Igor; Pittet-Cuenod, Brigitte; Delaloye, Jean-François

    2007-10-24

    Breast conserving surgery followed by radiation therapy is the treatment of choice for early breast cancer. For patients who choice or need a mastectomy, breast reconstruction provides an acceptable alternative. Breast cancer surgery has been evolving through minimally invasive approaches. Sentinel node biopsy has already remplaced axillary lymph node dissection in the evaluation of the axilla. Local ablation of the tumor may be a valuable alternative to surgery in the future.

  7. Breast Cancer and Bone Loss

    Science.gov (United States)

    ... Menopause Map Featured Resource Find an Endocrinologist Search Breast Cancer and Bone Loss July 2010 Download PDFs English ... G. Komen Foundation What is the link between breast cancer and bone loss? Certain treatments for breast cancer ...

  8. Genetics Home Reference: breast cancer

    Science.gov (United States)

    ... Email Facebook Twitter Home Health Conditions Breast cancer Breast cancer Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Breast cancer is a disease in which certain cells in ...

  9. Molecular imaging of breast cancer

    NARCIS (Netherlands)

    Munnink, T. H. Oude; Nagengast, W. B.; Brouwers, A. H.; Schroder, C. P.; Hospers, G. A.; Lub-de Hooge, M. N.; van der Wall, E.; van Diest, P. J.; de Vries, E. G. E.

    2009-01-01

    Molecular imaging of breast cancer can potentially be used for breast cancer screening, staging, restaging, response evaluation and guiding therapies. Techniques for molecular breast cancer imaging include magnetic resonance imaging (MRI), optical imaging, and radionuclide imaging with positron

  10. Breast cancer predisposition syndromes.

    Science.gov (United States)

    Hemel, Deborah; Domchek, Susan M

    2010-10-01

    A small, but important, percentage of breast cancer cases is caused by the inheritance of a single copy of a mutated gene. BRCA1 and BRCA2 are the genes most commonly associated with inherited breast cancer; however, mutations in TP53 and PTEN cause Li-Fraumeni syndrome and Cowden syndrome, respectively, both of which are associated with high lifetime risks of breast cancer. Advances in the field of breast cancer genetics have led to an improved understanding of detection and prevention strategies. More recently, strategies to target the underlying genetic defects in BRCA1- and BRCA2-associated breast and ovarian cancers are emerging and may have implications for certain types of sporadic breast cancer. Copyright 2010 Elsevier Inc. All rights reserved.

  11. ODAM Expression Inhibits Human Breast Cancer Tumorigenesis

    OpenAIRE

    Kestler, Daniel P; Foster, James S.; Bruker, Charles T.; Prenshaw, John W.; Kennel, Stephen J.; Wall, Jonathan S.; Weiss, Deborah T.; Alan Solomon

    2011-01-01

    We have posited that Odontogenic Ameloblast Associated Protein (ODAM) serves as a novel prognostic biomarker in breast cancer and now have investigated its potential role in regulating tumor growth and metastasis. Human breast cancer MDA-MB-231 cells were transfected with a recombinant ODAM plasmid construct (or, as a control, the plasmid vector alone). ODAM expression increased adhesion and apoptosis of the transfected MDA-MB-231 cells and suppressed their growth rate, migratory activity, an...

  12. Design of the SHAPE-2 study: the effect of physical activity, in addition to weight loss, on biomarkers of postmenopausal breast cancer risk

    NARCIS (Netherlands)

    van Gemert, Willemijn A.M.; Iestra, Jolein I.; Schuit, Albertine J.; May, Anne M.; Takken, Tim; Veldhuis, Wouter B.; van der Palen, Jacobus Adrianus Maria; Wittink, Harriet; Peeters, Petra H.M.; Monninkhof, Evelyn M.

    2013-01-01

    Background Physical inactivity and overweight are two known risk factors for postmenopausal breast cancer. Former exercise intervention studies showed that physical activity influences sex hormone levels, known to be related to postmenopausal breast cancer, mainly when concordant loss of body weight

  13. Breast cancer statistics, 2013.

    Science.gov (United States)

    DeSantis, Carol; Ma, Jiemin; Bryan, Leah; Jemal, Ahmedin

    2014-01-01

    In this article, the American Cancer Society provides an overview of female breast cancer statistics in the United States, including data on incidence, mortality, survival, and screening. Approximately 232,340 new cases of invasive breast cancer and 39,620 breast cancer deaths are expected to occur among US women in 2013. One in 8 women in the United States will develop breast cancer in her lifetime. Breast cancer incidence rates increased slightly among African American women; decreased among Hispanic women; and were stable among whites, Asian Americans/Pacific Islanders, and American Indians/Alaska Natives from 2006 to 2010. Historically, white women have had the highest breast cancer incidence rates among women aged 40 years and older; however, incidence rates are converging among white and African American women, particularly among women aged 50 years to 59 years. Incidence rates increased for estrogen receptor-positive breast cancers in the youngest white women, Hispanic women aged 60 years to 69 years, and all but the oldest African American women. In contrast, estrogen receptor-negative breast cancers declined among most age and racial/ethnic groups. These divergent trends may reflect etiologic heterogeneity and the differing effects of some factors, such as obesity and parity, on risk by tumor subtype. Since 1990, breast cancer death rates have dropped by 34% and this decrease was evident in all racial/ethnic groups except American Indians/Alaska Natives. Nevertheless, survival disparities persist by race/ethnicity, with African American women having the poorest breast cancer survival of any racial/ethnic group. Continued progress in the control of breast cancer will require sustained and increased efforts to provide high-quality screening, diagnosis, and treatment to all segments of the population. © 2013 American Cancer Society, Inc.

  14. Decreased expression of angiogenesis antagonist EFEMP1 in sporadic breast cancer is caused by aberrant promoter methylation and points to an impact of EFEMP1 as molecular biomarker.

    Science.gov (United States)

    Sadr-Nabavi, Ariane; Ramser, Juliane; Volkmann, Juliane; Naehrig, Joerg; Wiesmann, Frank; Betz, Beate; Hellebrand, Heide; Engert, Stefanie; Seitz, Susanne; Kreutzfeld, Rene; Sasaki, Takako; Arnold, Norbert; Schmutzler, Rita; Kiechle, Marion; Niederacher, Dieter; Harbeck, Nadia; Dahl, Edgar; Meindl, Alfons

    2009-04-01

    EGF-containing fibulin-like extracellular matrix protein 1 (EFEMP1) was recently described as an antagonist of angiogenesis. Motivated by a strong dependence of tumor growth and metastasis on angiogenesis, we investigated the role of EFEMP1 in human breast cancer. We applied RNA microarray expression analysis and quantitative real-time PCR (QRT) in a total of 45 sporadic breast cancer tissues and found EFEMP1 down-regulation in 59% and 61% of the analyzed tissues, respectively. This down-regulation was confirmed on protein level. Immunohistochemistry in 211 breast cancer tissues resulted in reduced or even abolished EFEMP1 expression in 57-62.5% of the tumors. Bisulphite genomic sequencing in breast cancer cell lines and primary breast cancer tissues revealed promoter methylation as the major cause of this down-regulation. Furthermore, analysis of 203 clinically well characterized primary breast cancers displayed a significant correlation of reduced EFEMP1 protein expression with poor disease-free (p = 0.037) and overall survival (p = 0.032), particularly in those node-positive patients who received adjuvant anthracycline-based chemotherapy, but not in those treated by either cyclophosphamide-methotrexate-5-fluorouracil (CMF) or Tamoxifen. In summary, the presented data demonstrate for the first time the reduced EFEMP1 expression on RNA and protein level in a substantial number of sporadic breast carcinomas and its correlation with epigenetic alterations. Furthermore, these data point towards a possible predictive impact of EFEMP1 expression in primary breast cancer.

  15. Neuroendocrine breast cancer.

    Science.gov (United States)

    Graça, Susana; Esteves, Joana; Costa, Sílvia; Vale, Sílvio; Maciel, Jorge

    2012-08-13

    Neuroendocrine breast cancer is thought to account for about 1% of all breast cancers. This rare type of breast malignancy is more common in older women and presents as a low-grade, slow-growing cancer. The most definitive markers that indicate neuroendocrine carcinoma are the presence of chromogranin, synaptophysin or neuron-specific enolase, in at least 50% of malignant tumour cells. The authors present a case report of an 83-year-old woman, admitted to their institution with right breast lump. Physical examination, mammography and ultrasonography showed a 2.4 cm nodule, probably a benign lesion (BI-RADS 3). A fine needle aspiration biopsy was performed and revealed proliferative epithelial papillary lesion. She was submitted to excisional biopsy and histology showed endocrine breast cancer well differentiated (G1). Immunohistochemically, tumour cells were positive for synaptophysin. These breast cancers are characterised for their excellent prognosis and conservative treatment is almost always enough to obtain patient cure.

  16. Distinct claudin expression characterizes BRCA1-related breast cancer

    NARCIS (Netherlands)

    van Voss, Marise R. Heerma; van Diest, Paul J.; Smolders, Yvonne H. C. M.; Bart, Joost; van der Wall, Elsken; van der Groep, Petra

    2014-01-01

    AimsMembers of the claudin family are involved in cancer progression and are differentially expressed in subtypes of breast cancer. Breast cancers in BRCA1 germ line mutation carriers have distinct clinicopathological characteristics. Biomarkers that discriminate between BRCA1-related and sporadic

  17. Increasing Breast Cancer Surveillance Among African American Breast Cancer Survivors

    Science.gov (United States)

    2010-01-01

    one or both breasts were affected. Family Member (e.g. grandmother, aunt) Paternal or Maternal Type or Location of Cancer (e.g. breast ...Local recurrences and distant metastases after breast -conserving surgery and radiation therapy for early breast cancer . Int J Radiat Oncol Biol Phys...AD_________________ AWARD NUMBER: DAMD17-03-1-0454 TITLE: Increasing Breast Cancer Surveillance

  18. Breast tissue-based microRNA panel highlights microRNA-23a and selected target genes as putative biomarkers for breast cancer.

    Science.gov (United States)

    Eissa, Sanaa; Matboli, Marwa; Shehata, Hanan H

    2015-03-01

    We explored the differential expression of breast tissue-based panel of microRNAs (miRNAs) and their potential application as prognostic markers of breast cancer (BC). This study was divided into the following phases: (1) A panel of 6 BC characteristic miRNAs, which were retrieved based on the microarray signature profiling (released by miRWalk), was explored using SYBR Green-based polymerase chain reaction (PCR) array in 16 cancerous and 16 noncancerous breast tissue; (2) pathway enrichment analysis of the key miRNA target genes; (3) marker choice and validation by real-time PCR in a larger set of 76 patients with BC, 36 benign breast conditions, and 36 healthy volunteers; (4) validation of miRNA (miR)-23a target genes (forkhead box m [FOXM1] and histidine-rich glycoprotein [HRG]) by conventional reverse transcriptase (RT)-PCR; and (5) the prognostic significance of the investigated parameters in the BC validation group was explored. In PCR array-based miRNA expression analysis, 4 miRNAs were found to be altered more than twice (miR-96, miR-29c, miR-221, and miR-23a). Bioinformatic analysis of the target genes revealed enrichment for special biological process categories, that is, cell cycle, angiogenesis, apoptosis, cell proliferation, and cell adhesion. miR-23a, HRG messenger RNA, and FOX messenger RNA were positive in BC by 82.9%, 72.4%, and 71.1%, respectively. The overall concordance rates between miR-23a with HRG and FOXM1 tissue RNAs were 91% and 79%, respectively. The median follow-up period was 49 months. mi-23a and HRG RNA were significant independent prognostic markers in relapse-free survival. miR-23a may have an oncogenic function and enhance BC progression by directly activating FOXM1 and HRG at RNA level. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Pilot Study on MAGE-C2 as a Potential Biomarker for Triple-Negative Breast Cancer

    Directory of Open Access Journals (Sweden)

    Qian Zhao

    2016-01-01

    Full Text Available Objective. In the current study, we measured the expression status of melanoma antigen gene c2 (MAGE-C2 in triple-negative breast cancer (TNBC and analyzed its prognostic with the clinical pathological features of patients with TNBC. Methods. The expressions statuses of MAGE-C2 were detected in TNBC tissues and paracarcinoma tissues by immunohistochemistry, reverse transcription-polymerase chain reaction (RT-PCR, and western blotting. Then, we investigated the relationship of MAGE-C2 expression status and clinicopathological parameters of TNBC patients by the chi-squared test. Finally, we discussed the relations of MAGE-C2 expression state and prognosis of patients with TNBC by Kaplan-Meier method and Cox proportional hazards model. Results. High MAGE-C2 expression was found in 38.18% (42/110 of TNBC tissues. In adjacent tissues it was 9.09% (10/110. High MAGE-C2 expression in TNBC patients was closely associated with lymph node status, tumor node metastasis (TNM stage, and lymphovascular invasion (P<0.001. TNBC patients with high MAGE-C2 expression had significantly shorter survival time than low expression patients. We also found that age, lymph node status, TNM stage, lymphovascular invasion, and MAGE-C2 expression status were closely associated with overall survival of TNBC patients (P<0.05. Conclusion. High MAGE-C2 expression may serve as an independent prognostic factor for TNBC patients.

  20. Other Considerations for Pregnancy and Breast Cancer

    Science.gov (United States)

    ... first 3 months of pregnancy . Other Information About Pregnancy and Breast Cancer Key Points Lactation (breast milk production) and breast- ... has had breast cancer. To Learn More About Breast Cancer and Pregnancy For more information from the National Cancer Institute ...

  1. General Information about Breast Cancer and Pregnancy

    Science.gov (United States)

    ... first 3 months of pregnancy . Other Information About Pregnancy and Breast Cancer Key Points Lactation (breast milk production) and breast- ... has had breast cancer. To Learn More About Breast Cancer and Pregnancy For more information from the National Cancer Institute ...

  2. PET scan for breast cancer

    Science.gov (United States)

    ... radioactive substance (called a tracer) to look for breast cancer. This tracer can help identify areas of cancer ... only after a woman has been diagnosed with breast cancer. It is done to see if the cancer ...

  3. BREAST CANCER AND EXERCISE

    Science.gov (United States)

    2008-03-19

    Prevent Osteoporosis and Osteoporotic Fractures; Improve Quality of Life; Improve Weight Control, and Muscular and Cardiovascular Fitness; Help the Patients to Return to Working Life; Reduce the Risk of Breast Cancer Recurrence; Prevent Other Diseases and Reduce All-Cause Mortality in Patients With Primary Breast Cancer.

  4. Male breast cancer

    DEFF Research Database (Denmark)

    Lautrup, Marianne D; Thorup, Signe S; Jensen, Vibeke

    2017-01-01

    Objective: Describe prognostic parameters of Danish male breast cancer patients (MBCP) diagnosed from 1980–2009. Determine all-cause mortality compared to the general male population and analyze survival/mortality compared with Danish female breast cancer patients (FBCP) in the same period...

  5. Synchronous bilateral breast cancer in a male

    Science.gov (United States)

    Rubio Hernández, María Caridad; Díaz Prado, Yenia Ivet; Pérez, Suanly Rodríguez; Díaz, Ronald Rodríguez; Aleaga, Zaili Gutiérrez

    2013-01-01

    Male breast cancer, which represents only 1% of all breast cancers, is occasionally associated with a family history of breast cancer. Sporadic male breast cancers presenting with another primary breast cancer are extremely rare. In this article, we report on a 70-year-old male patient with bilateral multifocal and synchronous breast cancer and without a family history of breast cancer. PMID:24319497

  6. BRCAness as a Biomarker for Predicting Prognosis and Response to Anthracycline-Based Adjuvant Chemotherapy for Patients with Triple-Negative Breast Cancer.

    Directory of Open Access Journals (Sweden)

    Hitomi Mori

    Full Text Available Triple-negative breast cancer (TNBC is a heterogeneous tumor that encompasses many different subclasses of the disease. In this study, we assessed BRCAness, defined as the shared characteristics between sporadic and BRCA1-mutated tumors, in a large cohort of TNBC cases.The BRCAness of 262 patients with primary TNBCs resected between January 2004 and December 2014 was determined through the isolation of DNA from tumor tissue. Classification of BRCAness was performed using multiple ligation-dependent probe amplification (MLPA. The tumor subtypes were determined immunohistochemically using resected specimens.Of the 262 TNBCs, the results of the MLPA assays showed that 174 (66.4% tumors had BRCAness. Patients with BRCAness tumors were younger than patients with non-BRCAness tumors (P = 0.003. There was no significant difference between the two groups regarding their pathological stages. The BRCAness group had a significantly shorter recurrence-free survival (RFS compared with the non-BRCAness group (P = 0.04 and had a shorter overall survival (OS although this did not reach statistical significance. Adjuvant treatments with anthracycline-based regimens provided significantly greater benefits to the BRCAness group (P = 0.003 for RFS, and P = 0.03 for OS. Multivariate Cox proportional hazard model analysis showed that BRCAness was an independent negative prognostic factor, and the anthracycline-based adjuvant chemotherapy was an independent positive prognostic factor for both RFS and OS in TNBC.The 66.4% patients of TNBCs showed BRCAness. BRCAness is essential as a biomarker in the subclassification of TNBCs and might be of use for predicting their prognosis. Furthermore, this biomarker might be a predictive factor for the effectiveness of anthracycline-based adjuvant chemotherapy for patients with TNBCs.

  7. CDC Vital Signs: Breast Cancer

    Science.gov (United States)

    ... 2.65 MB] Read the MMWR Science Clips Breast Cancer Black Women Have Higher Death Rates from Breast ... of Page U.S. State Info Number of Additional Breast Cancer Deaths Among Black Women, By State SOURCE: National ...

  8. Biomarkers in Cervical Cancer

    OpenAIRE

    Eun-Kyoung Yim; Jong-Sup Park

    2006-01-01

    Cervical cancer, a potentially preventable disease, remains the second most common malignancy in women worldwide. Human papillomavirus (HPV) is the single most important etiological agent in cervical cancer, contributing to neoplastic progression through the action of viral oncoproteins, mainly E6 and E7. Cervical screening programs using Pap smear testing have dramatically improved cervical cancer incidence and reduced deaths, but cervical cancer still remains a global health burden. The bio...

  9. Identification of Ras suppressor-1 (RSU-1) as a potential breast cancer metastasis biomarker using a three-dimensional in vitro approach

    Science.gov (United States)

    Gkretsi, Vasiliki; Stylianou, Andreas; Louca, Maria; Stylianopoulos, Triantafyllos

    2017-01-01

    Breast cancer (BC) is the most common malignant disease in women, with most patients dying from metastasis to distant organs, making discovery of novel metastasis biomarkers and therapeutic targets imperative. Extracellular matrix (ECM)-related adhesion proteins as well as tumor matrix stiffness are important determinants for metastasis. As traditional two-dimensional culture does not take into account ECM stiffness, we employed 3-dimensional collagen I gels of increasing concentration and stiffness to embed BC cells of different invasiveness (MCF-7, MDA-MB-231 and MDA-MB-231-LM2) or tumor spheroids. We tested the expression of cell-ECM adhesion proteins and found that Ras Suppressor-1 (RSU-1) is significantly upregulated in increased stiffness conditions. Interestingly, RSU-1 siRNA-mediated silencing inhibited Urokinase Plasminogen Activator, and metalloproteinase-13, whereas tumor spheroids formed from RSU-1-depleted cells lost their invasive capacity in all cell lines and stiffness conditions. Kaplan-Meier survival plot analysis corroborated our findings showing that high RSU-1 expression is associated with poor prognosis for distant metastasis-free and remission-free survival in BC patients. Taken together, our results indicate the important role of RSU-1 in BC metastasis and set the foundations for its validation as potential BC metastasis marker. PMID:28423706

  10. The Minnesota Green Tea Trial (MGTT), a randomized controlled trial of the efficacy of green tea extract on biomarkers of breast cancer risk: study rationale, design, methods, and participant characteristics.

    Science.gov (United States)

    Samavat, Hamed; Dostal, Allison M; Wang, Renwei; Bedell, Sarah; Emory, Tim H; Ursin, Giske; Torkelson, Carolyn J; Gross, Myron D; Le, Chap T; Yu, Mimi C; Yang, Chung S; Yee, Douglas; Wu, Anna H; Yuan, Jian-Min; Kurzer, Mindy S

    2015-10-01

    The Minnesota Green Tea Trial (MGTT) was a randomized, placebo-controlled, double-blinded trial investigating the effect of daily green tea extract consumption for 12 months on biomarkers of breast cancer risk. Participants were healthy postmenopausal women at high risk of breast cancer due to dense breast tissue with differing catechol-O-methyltransferase (COMT) genotypes. The intervention was a green tea catechin extract containing 843.0 ± 44.0 mg/day epigallocatechin gallate or placebo capsules for 1 year. Annual digital screening mammograms were obtained at baseline and month 12, and fasting blood and 24-h urine samples were provided at baseline and at months 6 and 12. Primary endpoints included changes in percent mammographic density, circulating endogenous sex hormones, and insulin-like growth factor axis proteins; secondary endpoints were changes in urinary estrogens and estrogen metabolites and circulating F2-isoprostanes, a biomarker of oxidative stress. The MGTT screened more than 100,000 mammograms and randomized 1,075 participants based on treatment (green tea extract vs. placebo), stratified by COMT genotype activity (high COMT vs. low/intermediate COMT genotype activity). A total of 937 women successfully completed the study and 138 dropped out (overall dropout rate = 12.8 %). In this paper we report the rationale, design, recruitment, participant characteristics, and methods for biomarker and statistical analyses.

  11. [Fibrocystic breast disease--breast cancer sequence].

    Science.gov (United States)

    Habor, V; Habor, A; Copotoiu, C; Panţîru, A

    2010-01-01

    Fibrocystic breast disease has developed a major issue: the breast cancer sequence. Its involvement regarding the increse of breast cancer risk has 2 aspects: it may be either the marker of a prone tissue or a premalignant hystological deffect. Difficult differential diagnosis of benign proliferative breast lession and carcinoma led to the idea of sequency between the two: cancer does not initiate on normal mammary epithelia; it takes several proliferative stages for it to occur. In our series we analized a number of 677 breast surgical procedures where the pathologic examination reveals 115 cases (17%) of coexistence between cancer and fibrocystic breast disease. This aspect has proved to be related to earlier debut of breast cancer, suggesting that epithelial hyperplasia is a risk factor for breast cancer.

  12. Breast cancer stem cells

    Directory of Open Access Journals (Sweden)

    Thomas W Owens

    2013-08-01

    Full Text Available Cancer metastasis, resistance to therapies and disease recurrence are significant hurdles to successful treatment of breast cancer. Identifying mechanisms by which cancer spreads, survives treatment regimes and regenerates more aggressive tumours are critical to improving patient survival. Substantial evidence gathered over the last 10 years suggests that breast cancer progression and recurrence is supported by cancer stem cells (CSCs. Understanding how CSCs form and how they contribute to the pathology of breast cancer will greatly aid the pursuit of novel therapies targeted at eliminating these cells. This review will summarise what is currently known about the origins of breast CSCs, their role in disease progression and ways in which they may be targeted therapeutically.

  13. Breast reconstruction after breast cancer.

    Science.gov (United States)

    Serletti, Joseph M; Fosnot, Joshua; Nelson, Jonas A; Disa, Joseph J; Bucky, Louis P

    2011-06-01

    After reading this article, the participant should be able to: 1. Describe the mental, emotional, and physical benefits of reconstruction in breast cancer patients. 2. Compare the most common techniques of reconstruction in patients and detail benefits and risks associated with each. 3. Outline different methods of reconstruction and identify the method considered best for the patient based on timing of the procedures, body type, adjuvant therapies, and other coexisting conditions. 4. Distinguish between some of the different flaps that can be considered for autologous reconstruction. Breast cancer is unfortunately a common disease affecting millions of women, often at a relatively young age. Reconstruction following mastectomy offers women an opportunity to mollify some of the emotional and aesthetic effects of this devastating disease. Although varying techniques of alloplastic and autologous techniques are available, all strive to achieve the same goal: the satisfactory reformation of a breast mound that appears as natural as possible without clothing and at the very least is normal in appearance under clothing. This article summarizes the various approaches to breast reconstruction and offers a balanced view of the risks and benefits of each, all of which in the end offer the opportunity for excellent and predictable results with a high degree of patient satisfaction.

  14. Breast cancer: equal rights?

    Directory of Open Access Journals (Sweden)

    Ana Fátima Carvalho Fernandes

    2015-02-01

    Full Text Available There is not any statistics related to encouraging breast cancer along the past century, and there has not been any in present century. It has been published in the scientific and lay press information on the crescent number of women attacked by breast cancer. How to spare women and family members of such pain when they experience this disease? Which rights provide assistance to the women with cancer?

  15. Oxalate induces breast cancer.

    Science.gov (United States)

    Castellaro, Andrés M; Tonda, Alfredo; Cejas, Hugo H; Ferreyra, Héctor; Caputto, Beatriz L; Pucci, Oscar A; Gil, German A

    2015-10-22

    Microcalcifications can be the early and only presenting sign of breast cancer. One shared characteristic of breast cancer is the appearance of mammographic mammary microcalcifications that can routinely be used to detect breast cancer in its initial stages, which is of key importance due to the possibility that early detection allows the application of more conservative therapies for a better patient outcome. The mechanism by which mammary microcalcifications are formed is still largely unknown but breast cancers presenting microcalcifications are more often associated with a poorer prognosis. We combined Capillary Electrochromatography, histology, and gene expression (qRT-PCR) to analyze patient-matched normal breast tissue vs. breast tumor. Potential carcinogenicity of oxalate was tested by its inoculation into mice. All data were subjected to statistical analysis. To study the biological significance of oxalates within the breast tumor microenvironment, we measured oxalate concentration in both human breast tumor tissues and adjoining non-pathological breast tissues. We found that all tested breast tumor tissues contain a higher concentration of oxalates than their counterpart non-pathological breast tissue. Moreover, it was established that oxalate induces proliferation of breast cells and stimulates the expression of a pro-tumorigenic gene c-fos. Furthermore, oxalate generates highly malignant and undifferentiated tumors when it was injected into the mammary fatpad in female mice, but not when injected into their back, indicating that oxalate does not induce cancer formation in all types of tissues. Moreover, neither human kidney-epithelial cells nor mouse fibroblast cells proliferate when are treated with oxalate. We found that the chronic exposure of breast epithelial cells to oxalate promotes the transformation of breast cells from normal to tumor cells, inducing the expression of a proto-oncogen as c-fos and proliferation in breast cancer cells

  16. Relationship between thiol, tyrosine nitration and carbonyl formation as biomarkers of oxidative stress and changes of hemostatic function of plasma from breast cancer patients before surgery.

    Science.gov (United States)

    Kedzierska, Magdalena; Olas, Beata; Wachowicz, Barbara; Jeziorski, Arkadiusz; Piekarski, Janusz

    2012-02-01

    In breast cancer patients dysregulation of reactive oxygen species metabolism, as detected by various indicators in plasma or various blood cells, including red blood cells and blood platelets, is observed. The aim of our study was to explain the effect of oxidative/nitrative stress on hemostatic activity of plasma from breast cancer patients. Different methods were used to analyze oxidative/nitrative stress (carbonyl groups and 3-nitrotyrosine levels - ELISA and C-ELISA method, respectively and free thiol groups was estimated with 5,5'-dithio-bis(2-nitro-benzoic acid)). We also measured total antioxidant status (TAS) in plasma. Our results showed the correlation between the oxidative stress and changes of hemostasis in breast cancer patients; the correlation between the increased amount of carbonylated or nitrated plasma proteins and fibrin polymerization or lysis in plasma isolated from invasive breast cancer patients. We also observed that the relationship between TAS and fibrin polymerization or lysis in plasma from invasive breast cancer exists. Considering the data presented in this study, we suggest that the oxidative/nitrative stress in breast cancer patients may induce the changes of hemostasis in these patients. Published by Elsevier Inc.

  17. Early Detection of Breast Cancer Using Molecular Beacons

    National Research Council Canada - National Science Library

    Yang, Lily

    2008-01-01

    .... This method can also be used to examine the level of gene expression in real time within living breast cancer cells such that changes in the expression of specific biomarker genes can be monitored...

  18. High Intratumoral Stromal Content Defines Reactive Breast Cancer as a Low-risk Breast Cancer Subtype | Office of Cancer Genomics

    Science.gov (United States)

    Improved biomarker tests are required to minimize overdiagnosis and overtreatment of breast cancers. A number of pathologic criteria have been established to differentiate indolent or aggressive behavior, such as Nottingham grade of cancer cells. However, the effects of the tumor microenvironment on patient outcomes have not been integrated into pathologic criteria. In the current study, the Reactive subtype of breast cancer, identified by reverse-phase protein arrays, was demonstrated to indicate a favorable outcome.

  19. Drugs Approved for Breast Cancer

    Science.gov (United States)

    ... Ask about Your Treatment Research Drugs Approved for Breast Cancer This page lists cancer drugs approved by the ... are not listed here. Drugs Approved to Prevent Breast Cancer Evista (Raloxifene Hydrochloride) Keoxifene (Raloxifene Hydrochloride) Nolvadex (Tamoxifen ...

  20. Breast Cancer in Young Women

    Science.gov (United States)

    ... Campaign Initiatives Participation in Cancer Moonshot Stay Informed Breast Cancer in Young Women Recommend on Facebook Tweet Share Compartir Syndicate this page Marleah’s family history of breast cancer was her motivation for pursuing a career where ...

  1. Receptor conversion in distant breast cancer metastases

    NARCIS (Netherlands)

    Hoefnagel, L.D.C.

    2013-01-01

    The routine pathological work-up of breast cancer includes the evaluation of the estrogen receptor (ERα), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) which reveals biological information about the tumour as well as provides predictive biomarkers regarding hormonal

  2. Broccoli Sprout Extract in Treating Patients With Breast Cancer

    Science.gov (United States)

    2017-08-30

    Ductal Breast Carcinoma; Ductal Breast Carcinoma In Situ; Estrogen Receptor Negative; Estrogen Receptor Positive; Invasive Breast Carcinoma; Lobular Breast Carcinoma; Postmenopausal; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer

  3. Dietary influence on estrogens and cytokines in breast cancer

    Directory of Open Access Journals (Sweden)

    Xin Nian

    2017-07-01

    Full Text Available Breast cancer affects one out of eight women in their lifetime. Many factors contribute to the development of breast cancer, such as hereditary mutations and lifetime exposure to environmental factors, including estrogen. In addition, overweight and obesity, especially with increased waist circumference, are known to be associated with breast cancer risk. This review will summarize our understanding of the effect of diet on breast cancer incidence and progression. Since some inflammatory cytokines that are changed by a high-fat diet are known to promote the growth of breast cancer cells, these cytokines may serve as biomarkers to monitor the dietary influence for women at high risk of breast cancer and as future therapeutic targets for breast cancer treatment.

  4. Treatment Options for Male Breast Cancer

    Science.gov (United States)

    ... Breast & Gynecologic Cancers Breast Cancer Screening Research Male Breast Cancer Treatment (PDQ®)–Patient Version General Information about Male Breast Cancer Go to Health Professional Version Key Points Male ...

  5. Breast Cancer Research Program

    Science.gov (United States)

    2010-09-01

    treatment with the nonsteroidal anti-inflamma- tory drugs (NSAIDs) ibuprofen or aspirin reduces this inflammatory response and, possibly, postpartum breast...involution with systemic ibuprofen or aspirin did not interrupt mammary epithelial cell regression that normally occurs during this period These data... children of immigrant stress, and social desirability bias. Preliminary data suggest that breast cancer survivors, notably racial/ethnic minorities

  6. Flax and Breast Cancer: A Systematic Review.

    Science.gov (United States)

    Flower, Gillian; Fritz, Heidi; Balneaves, Lynda G; Verma, Shailendra; Skidmore, Becky; Fernandes, Rochelle; Kennedy, Deborah; Cooley, Kieran; Wong, Raimond; Sagar, Stephen; Fergusson, Dean; Seely, Dugald

    2014-05-01

    Flax is a food and dietary supplement commonly used for menopausal symptoms. Flax is known for its lignan, α-linolenic acid, and fiber content, components that may possess phytogestrogenic, anti-inflammatory, and hormone modulating effects, respectively. We conducted a systematic review of flax for efficacy in improving menopausal symptoms in women living with breast cancer and for potential impact on risk of breast cancer incidence or recurrence. We searched MEDLINE, Embase, the Cochrane Library, and AMED from inception to January 2013 for human interventional or observational data pertaining to flax and breast cancer. Of 1892 records, we included a total of 10 studies: 2 randomized controlled trials, 2 uncontrolled trials, 1 biomarker study, and 5 observational studies. Nonsignificant (NS) decreases in hot flash symptomatology were seen with flax ingestion (7.5 g/d). Flax (25 g/d) increased tumor apoptotic index (Pflax or 50 mg secoisolariciresinol diglycoside daily. Observational data suggests associations between flax and decreased risk of primary breast cancer (adjusted odds ratio [AOR] = 0.82; 95% confidence interval [CI] = 0.69-0.97), better mental health (AOR = 1.76; 95% CI = 1.05-2.94), and lower mortality (multivariate hazard ratio = 0.69; 95% CI = 0.50-0.95) among breast cancer patients. Current evidence suggests that flax may be associated with decreased risk of breast cancer. Flax demonstrates antiproliferative effects in breast tissue of women at risk of breast cancer and may protect against primary breast cancer. Mortality risk may also be reduced among those living with breast cancer. © The Author(s) 2013.

  7. Lymphedema after breast cancer

    National Research Council Canada - National Science Library

    Brahmi, Sami Aziz; Ziani, Fatima Zahra

    2016-01-01

    Image in medicine Lymphedema is one of the most significant survivorship issues after the surgical treatment of breast cancer and in this population it has been documented to have significant quality...

  8. Learning about Breast Cancer

    Science.gov (United States)

    Skip to main content Learning About Breast Cancer Enter Search Term(s): Español Research Funding An Overview Bioinformatics Current Grants Education and Training Funding Extramural Research News Features Funding Divisions Funding ...

  9. Preeclampsia and breast cancer

    DEFF Research Database (Denmark)

    Pacheco, Nadja Livia Pekkola; Andersen, Anne-Marie Nybo; Kamper-Jørgensen, Mads

    2015-01-01

    BACKGROUND: In parous women preeclampsia has been associated with reduced risk of developing breast cancer. Characteristics of births following preeclamptic pregnancies may help understand mechanisms involved in the breast cancer risk reduction inferred by preeclampsia. METHODS: We conducted...... a register-based cohort study of all Danish women giving birth during 1978-2010 (n = 778,701). The association between preeclampsia and breast cancer was evaluated overall and according to birth characteristics by means of incidence rate ratios (IRR) estimated in Poisson regression models. RESULTS: Compared......, and in women giving birth to boys. These findings, however, did not reach statistical significance. Finally, risk reduction was slightly greater following milder forms of preeclampsia. CONCLUSION: Our data is compatible with an approximately 20% reduction in risk of developing breast cancer following...

  10. [Pregnancy and breast cancer].

    Science.gov (United States)

    Ramírez-Torres, Nicolás; Asbun-Bojalil, Juan; Hernández-Valencia, Marcelino

    2013-01-01

    association of breast cancer and pregnancy is not common. The objective of this investigation was to evaluate the pregnancy, young age, stage, treatment, prognosis and mortality of women with breast cancer during pregnancy. retrospective analysis from March 1992 to February 2009, 16 patients were included with breast cancer and pregnancy. They were analized: histological characteristic of tumor, therapeutic response of the oncological treatment, evolution of the pregnancy. From of baby born: Apgar and weight. The woman's mortality with breast cancer during pregnancy was evaluated for age group and for interval of time between late pregnancy and diagnosis posterior of breast cancer and pregnancy. characteristic predominant clinicohistological: stage III (81.2%), T3-T4 (75%), N+ 93.7%, invasive ductal carcinoma (87.5%), histological grade 2-3 (93.7%), receptor estrogeno positive (43.7%); RPpositive (25%); HER-2/neu positive (31.2%). 27 chemotherapy cycles were applied with 5-fluorouracil, epirubicin and cyclophosphamide during the second or third trimester of the pregnancy, there were not severe adverse effects for the mothers and the baby born exposed to chemotherapy. The mean time to disease recurrence was 18.8 months (range, 6-62 months). The rate of mortality for specific age (breast cancer and pregnancy.

  11. Randomized Trial Comparing Telephone Versus In-Person Weight Loss Counseling on Body Composition and Circulating Biomarkers in Women Treated for Breast Cancer: The Lifestyle, Exercise, and Nutrition (LEAN) Study.

    Science.gov (United States)

    Harrigan, Maura; Cartmel, Brenda; Loftfield, Erikka; Sanft, Tara; Chagpar, Anees B; Zhou, Yang; Playdon, Mary; Li, Fangyong; Irwin, Melinda L

    2016-03-01

    Obesity is associated with a higher risk of breast cancer mortality. The gold standard approach to weight loss is in-person counseling, but telephone counseling may be more feasible. We examined the effect of in-person versus telephone weight loss counseling versus usual care on 6-month changes in body composition, physical activity, diet, and serum biomarkers. One hundred breast cancer survivors with a body mass index ≥ 25 kg/m(2) were randomly assigned to in-person counseling (n = 33), telephone counseling (n = 34), or usual care (UC) (n = 33). In-person and telephone counseling included 11 30-minute counseling sessions over 6 months. These focused on reducing caloric intake, increasing physical activity, and behavioral therapy. Body composition, physical activity, diet, and serum biomarkers were measured at baseline and 6 months. The mean age of participants was 59 ± 7.5 years old, with a mean BMI of 33.1 ± 6.6 kg/m(2), and the mean time from diagnosis was 2.9 ± 2.1 years. Fifty-one percent of the participants had stage I breast cancer. Average 6-month weight loss was 6.4%, 5.4%, and 2.0% for in-person, telephone, and UC groups, respectively (P = .004, P = .009, and P = .46 comparing in-person with UC, telephone with UC, and in-person with telephone, respectively). A significant 30% decrease in C-reactive protein levels was observed among women randomly assigned to the combined weight loss intervention groups compared with a 1% decrease among women randomly assigned to UC (P = .05). Both in-person and telephone counseling were effective weight loss strategies, with favorable effects on C-reactive protein levels. Our findings may help guide the incorporation of weight loss counseling into breast cancer treatment and care. © 2015 by American Society of Clinical Oncology.

  12. Down-regulation of hK7 in the sera of breast cancer and benign breast disease patients

    Directory of Open Access Journals (Sweden)

    Samina Ejaz

    2017-07-01

    Conclusions: Down regulation of hK7 suggests the possible role of this protein in natural course of breast cancer and benign breast diseases. Study should be extended on large-scale to confirm the potential of hK7 as biomarker of breast cancer.

  13. PET Metabolic Biomarkers for Cancer

    Directory of Open Access Journals (Sweden)

    Etienne Croteau

    2016-01-01

    Full Text Available The body's main fuel sources are fats, carbohydrates (glucose, proteins, and ketone bodies. It is well known that an important hallmark of cancer cells is the overconsumption of glucose. Positron emission tomography (PET imaging using the glucose analog 18 F-fluorodeoxyglucose ( 18 F-FDG has been a powerful cancer diagnostic tool for many decades. Apart from surgery, chemotherapy and radiotherapy represent the two main domains for cancer therapy, targeting tumor proliferation, cell division, and DNA replication–-all processes that require a large amount of energy. Currently, in vivo clinical imaging of metabolism is performed almost exclusively using PET radiotracers that assess oxygen consumption and mechanisms of energy substrate consumption. This paper reviews the utility of PET imaging biomarkers for the detection of cancer proliferation, vascularization, metabolism, treatment response, and follow-up after radiation therapy, chemotherapy, and chemotherapy-related side effects.

  14. Biomarkers in Advanced Larynx Cancer

    Science.gov (United States)

    Bradford, Carol R.; Kumar, Bhavna; Bellile, Emily; Lee, Julia; Taylor, Jeremy; D’Silva, Nisha; Cordell, Kitrina; Kleer, Celina; Kupfer, Robbi; Kumar, Pawan; Urba, Susan; Worden, Francis; Eisbruch, Avraham; Wolf, Gregory T.; Teknos, Theodoros N.; Prince, Mark E.P.; Chepeha, Douglas B.; Hogikyan, Norman D.; Moyer, Jeffrey S.; Carey, Thomas E.

    2014-01-01

    Objectives/Hypothesis To determine if tumor biomarkers were predictive of outcome in a prospective cohort of patients with advanced larynx cancer treated in a phase II clinical trial. Study Design Prospectively collected biopsy specimens from 58 patients entered into a Phase II trial of organ preservation in advanced laryngeal cancer were evaluated for expression of a large panel of biomarkers and correlations with outcome were determined. Methods Tissue microarrays were constructed from pretreatment biopsies and stained for cyclin D1, CD24, EGFR, MDM2, PCNA, p53, survivin, Bcl-xL, Bcl-2, BAK, rhoC, and NFκB. Pattern of invasion and p53 mutations were assessed. Correlations with overall survival (OS), disease-specific survival (DSS), time free from indication of surgery, induction chemotherapy response, and chemoradiation response were determined. Cox models were used to assess combinations of these biomarkers. Results Low expression of BAK was associated with response to induction chemotherapy. Low expression of BAK and cytoplasmic NFκB was associated with chemoradiation response. Aggressive histologic growth pattern was associated with response induction chemotherapy. Expression of cyclin D1 was predictive of overall and disease-specific survival. Overexpression of EGFR was also associated with an increased risk of death from disease. Bcl-xL expression increased significantly in persistent/recurrent tumors specimens when compared to pretreatment specimens derived from the same patient (p = 0.0003). Conclusions Evaluation of biomarker expression in pretreatment biopsy specimens can lend important predictive and prognostic information for patients with advanced larynx cancer. PMID:23775802

  15. The value of TOP2A gene copy number variation as a biomarker in breast cancer: Update of DBCG trial 89D

    DEFF Research Database (Denmark)

    Nielsen, K.V.; Ejlertsen, B.; Moller, S.

    2008-01-01

    BACKGROUND: Previous analyses of TOP2A and HER2 in the Danish Breast Cancer Coopererative Group (DBCG) trial 89D suggested that TOP2A amplifications and possible also deletions are predictive markers for the effect of adjuvant epirubicin in patients with primary breast cancer. We present an updated...... breast cancer, favoring treatment with epirubicin in patients with TOP2A amplifications, and perhaps deletions. Additional studies are needed to clarify the exact importance of TOP2A deletions on outcome, but deletions have proven to be associated with a very poor prognosis Udgivelsesdato: 2008...... and extended statistical analysis, requested for IVD-labeling of TOP2A testing. MATERIAL AND METHODS: In the DBCG trial 89D 980 Danish patients were randomly assigned to nine cycles of intravenous CMF (cyclophosphamide, methotrexate, and fluorouracil) or CEF (cyclophosphamide, epirubicin, and fluorouracil...

  16. Stereotactic Image-Guided Navigation During Breast Reconstruction in Patients With Breast Cancer

    Science.gov (United States)

    2017-04-12

    Ductal Breast Carcinoma in Situ; Lobular Breast Carcinoma in Situ; Recurrent Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer

  17. Serologic autoantibodies as diagnostic cancer biomarkers--a review.

    Science.gov (United States)

    Zaenker, Pauline; Ziman, Melanie R

    2013-12-01

    Current diagnostic techniques used for the early detection of cancers are successful but subject to detection bias. A recent focus lies in the development of more accurate diagnostic tools. An increase in serologic autoantibody levels has been shown to precede the development of cancer disease symptoms. Therefore, autoantibody levels in patient blood serum have been proposed as diagnostic biomarkers for early-stage diagnosis of cancers. Their clinical application has, however, been hindered by low sensitivity, specificity, and low predictive value scores. These scores have been shown to improve when panels of multiple diagnostic autoantibody biomarkers are used. A five-marker biomarker panel has been shown to increase the sensitivity of prostate cancer diagnosis to 95% as compared with 12.2% for prostate-specific antigen alone. New potential biomarker panels were also discovered for lung, colon, and stomach cancer diagnosis with sensitivity of 76%, 65.4%, and 50.8%, respectively. Studies in breast and liver cancer, however, seem to favor single markers, namely α-2-HS-glycoprotein and des-γ-carboxyprothrombin with sensitivities of 79% and 89% for the early detection of the cancers. The aim of this review is to discuss the relevance of autoantibodies in cancer diagnosis and to outline the current methodologies used in the detection of autoantibodies. The review concludes with a discussion of the autoantibodies currently used in the diagnosis of cancers of the prostate, breast, lung, colon, stomach, and liver. A discussion of the potential future use of autoantibodies as diagnostic cancer biomarkers is also included in this review. ©2013 AACR.

  18. Viruses and Breast Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Lawson, James S., E-mail: james.lawson@unsw.edu.au; Heng, Benjamin [School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney (Australia)

    2010-04-30

    Viruses are the accepted cause of many important cancers including cancers of the cervix and anogenital area, the liver, some lymphomas, head and neck cancers and indirectly human immunodeficiency virus associated cancers. For over 50 years, there have been serious attempts to identify viruses which may have a role in breast cancer. Despite these efforts, the establishment of conclusive evidence for such a role has been elusive. However, the development of extremely sophisticated new experimental techniques has allowed the recent development of evidence that human papilloma virus, Epstein-Barr virus, mouse mammary tumor virus and bovine leukemia virus may each have a role in the causation of human breast cancers. This is potentially good news as effective vaccines are already available to prevent infections from carcinogenic strains of human papilloma virus, which causes cancer of the uterine cervix.

  19. Dutch digital breast cancer screening: implications for breast cancer care

    NARCIS (Netherlands)

    Timmers, Johanna M.; den Heeten, Gerard J.; Adang, Eddy M.; Otten, Johannes D.; Verbeek, André L.; Broeders, Mireille J.

    2012-01-01

    Background: In comparison to other European population-based breast cancer screening programmes, the Dutch programme has a low referral rate, similar breast cancer detection and a high breast cancer mortality reduction. The referral rate in the Netherlands has increased over time and is expected to

  20. Expression of the breast cancer resistance protein in breast cancer

    NARCIS (Netherlands)

    Faneyte, Ian F.; Kristel, Petra M. P.; Maliepaard, Marc; Scheffer, George L.; Scheper, Rik J.; Schellens, Jan H. M.; van de Vijver, Marc J.

    2002-01-01

    PURPOSE: The breast cancer resistance protein (BCRP) is involved in in vitro multidrug resistance and was first identified in the breast cancer cell line MCF7/AdrVp. The aim of this study was to investigate the role of BCRP in resistance of breast cancer to anthracycline treatment. EXPERIMENTAL

  1. Breast cancer and pregnancy.

    Science.gov (United States)

    Knabben, Laura; Mueller, Michel D

    2017-08-29

    Background In the past decades the incidence of pregnancy-associated breast cancer (PABC) increased. Possible explanations are the trend to postpone childbearing and the general increase in the incidence of breast cancer. Materials and methods A sytematic review of the literature was performed with the aim to report on incidence, diagnosis, treatment and prognosis of breast cancer during pregnancy. We also cover the issue of pregnancy following a diagnosis of breast cancer including fertility preservation and prognosis. Results Ultrasound is the imaging method of choice in pregnancy, but mammography can also be performed as the fetal irradiation dose is low. To avoid a delay in diagnosis every sonographic mass in pregnant women which does not clearly correspond to a cyst needs further investigation by biopsy. Treatment should follow as close as possible the guidelines for non-pregnant patients. Administration of chemotherapy is possible after the first trimester. There is a large body of evidence for the use of anthracyclines. In contrast radiotherapy, trastuzumab and antihormonal treatment by tamoxifen are contraindicated during pregnancy. Pregnancy does not seem to influence prognosis. Most adverse obstetric outcomes are related to preterm delivery, which should therefore, whenever possible, be avoided. Young patients with breast cancer and incomplete family planning should be referred for counseling about fertility preservation options before the initiation of adjuvant treatment. A pregnancy following breast cancer does not have a negative impact on prognosis. Conclusion Multidisciplinary management of women with breast cancer in pregnancy is mandatory and data should be collected to allow further improvement in management.

  2. Preventing Breast Cancer: Making Progress

    Science.gov (United States)

    ... Navigation Bar Home Current Issue Past Issues Preventing Breast Cancer: Making Progress Past Issues / Fall 2006 Table of ... 000 women will have been diagnosed with invasive breast cancer, and nearly 41,000 women will die from ...

  3. Life After Breast Cancer Treatment

    Science.gov (United States)

    FACTS FOR LIFE Life After Breast Cancer Treatment Once breast cancer treatment ends, you may face a new set of issues and concerns. ... fear. If fear starts to disrupt your daily life, talk with your doctor. Getting the support and ...

  4. Progress in breast cancer: overview

    National Research Council Canada - National Science Library

    Arteaga, Carlos L

    2013-01-01

    This edition of CCR Focus titled Research in Breast Cancer: Frontiers in Genomics, Biology, and Clinical Investigation reviews six topics that cover areas of translational research of high impact in breast cancer...

  5. Inflammatory breast cancer: an overview

    NARCIS (Netherlands)

    Uden, D.J. van; Laarhoven, H.W.M. van; Westenberg, A.H.; Wilt, J.H. de; Blanken-Peeters, C.F.

    2015-01-01

    Inflammatory breast cancer (IBC) is the most aggressive entity of breast cancer. Management involves coordination of multidisciplinary management and usually includes neoadjuvant chemotherapy, ablative surgery if a tumor-free resection margin is expected and locoregional radiotherapy. This

  6. Adenoid cystic breast cancer.

    Science.gov (United States)

    McClenathan, James H; de la Roza, Gustavo

    2002-06-01

    Adenoid cystic carcinoma is a rare type of breast cancer that is generally reported in individual case reports or as series from major referral centers. To characterize early diagnostic criteria for adenoid cystic carcinoma and to determine whether breast-preserving surgery with radiotherapy is as effective as mastectomy for eradicating the disease, we reviewed clinical records of a large series of patients treated for adenoid cystic carcinoma of the breast at a large health maintenance organization (HMO) that includes primary care facilities and referral centers. Using the data bank of the Northern California Cancer Registry of the Kaiser Permanente Northern California Region (KPNCR), we retrospectively reviewed medical records of patients treated for adenoid cystic carcinoma of the breast. Follow-up also was done for these patients. Adenoid cystic carcinoma of the breast was diagnosed in 22 of 27,970 patients treated for breast cancer at KPNCR from 1960 through 2000. All 22 patients were female and were available for follow-up. Mean age of patients at diagnosis was 61 years (range, 37 to 94 years). In 17 (77%) of the women, a lump in the breast led to initial suspicion of a tumor; in 4 (23%) of the 22 patients, mammography led to suspicion of a tumor. Median tumor size was 20 mm. Pain was a prominent symptom. Surgical management evolved from radical and modified radical mastectomy to simple mastectomy or lumpectomy during the study period, during which time 1 patient died of previous ordinary ductal carcinoma of the contralateral breast, and 7 died of unrelated disease. At follow-up, 12 of the 13 remaining patients were free of disease; 1 patient died of the disease; and 1 patient remained alive despite late occurrence of lymph node and pulmonary metastases. Whether breast-preserving surgery with radiotherapy is as effective as mastectomy for treating adenoid cystic carcinoma of the breast has not been determined.

  7. Kindness Interventions in Enhancing Well-Being in Breast Cancer Survivors

    Science.gov (United States)

    2017-12-05

    Cancer Survivor; Stage 0 Breast Cancer; Stage I Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer

  8. Cardiac Rehabilitation Program in Improving Cardiorespiratory Fitness in Stage 0-III Breast Cancer Survivors

    Science.gov (United States)

    2017-08-17

    Cancer Survivor; Stage 0 Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

  9. PSA and beyond: alternative prostate cancer biomarkers

    Science.gov (United States)

    2016-01-01

    Background The use of biomarkers for prostate cancer screening, diagnosis and prognosis has the potential to improve the clinical management of the patients. Owing to inherent limitations of the biomarker prostate-specific antigen (PSA), intensive efforts are currently directed towards a search for alternative prostate cancer biomarkers, particularly those that can predict disease aggressiveness and drive better treatment decisions. Methods A literature search of Medline articles focused on recent and emerging advances in prostate cancer biomarkers was performed. The most promising biomarkers that have the potential to meet the unmet clinical needs in prostate cancer patient management and/or that are clinically implemented were selected. Conclusions With the advent of advanced genomic and proteomic technologies, we have in recent years seen an enormous spurt in prostate cancer biomarker research with several promising alternative biomarkers being discovered that show an improved sensitivity and specificity over PSA. The new generation of biomarkers can be tested via serum, urine, or tissue-based assays that have either received regulatory approval by the US Food and Drug Administration or are available as Clinical Laboratory Improvement Amendments-based laboratory developed tests. Additional emerging novel biomarkers for prostate cancer, including circulating tumor cells, microRNAs and exosomes, are still in their infancy. Together, these biomarkers provide actionable guidance for prostate cancer risk assessment, and are expected to lead to an era of personalized medicine. PMID:26790878

  10. Immunophenotyping of hereditary breast cancer

    NARCIS (Netherlands)

    van der Groep, P.|info:eu-repo/dai/nl/304810789

    2009-01-01

    Hereditary breast cancer runs in families where several family members in different generations are affected. Most of these breast cancers are caused by mutations in the high penetrance genes BRCA1 and BRCA2 which account for about 5% of all breast cancers. However, mutations in BRCA1 and BRCA2 may

  11. Clinical proteomics in breast cancer

    NARCIS (Netherlands)

    Gast, M.C.W.

    2009-01-01

    Breast cancer imposes a significant healthcare burden on women worldwide. Early detection is of paramount importance in reducing mortality, yet the diagnosis of breast cancer is hampered by a lack of adequate detection methods. In addition, better breast cancer prognostication may improve selection

  12. Breast cancer in the elderly

    African Journals Online (AJOL)

    breast cancer at the University of Benin Teaching Hospital, Nigeria. Of these, 27. (25.2%) were aged 60 years ... and physician vigilance are keys to early detection and treatment of breast cancer in the elderly. INTRODUCTION ..... Law TM, Hesketli PJ, Porter KA, Lawn-Tsao L,. McAxiaw R and Lopez MJ. Breast cancer in eld ...

  13. Omega-3 Fatty Acid in Treating Patients With Stage I-III Breast Cancer

    Science.gov (United States)

    2017-05-30

    Ductal Breast Carcinoma in Situ; Lobular Breast Carcinoma in Situ; Male Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

  14. Hypofractionated Radiation Therapy in Treating Patients With Stage 0-IIB Breast Cancer

    Science.gov (United States)

    2017-12-05

    Ductal Breast Carcinoma In Situ; Invasive Breast Carcinoma; Stage 0 Breast Cancer; Stage I Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer

  15. Pregnancy associated breast cancer and pregnancy after breast cancer treatment

    Science.gov (United States)

    Doğer, Emek; Çalışkan, Eray; Mallmann, Peter

    2011-01-01

    Breast cancer is one of the most common cancers diagnosed during pregnancy and its frequency is increasing as more women postpone their pregnancies to their thirties and forties. Breast cancer diagnosis during pregnancy and lactation is difficult and complex both for the patient and doctors. Delay in diagnosis is frequent and treatment modalities are difficult to accept for the pregnant women. The common treatment approach is surgery after diagnosis, chemotherapy after the first trimester and radiotherapy after delivery. Even though early stage breast cancers have similar prognosis, advanced stage breast cancers diagnosed during pregnancy and lactation have poorer prognosis than similar stage breast cancers diagnosed in non-pregnant women. Women who desire to become pregnant after treatment of breast cancer will have many conflicts. Although the most common concern is recurrence of breast cancer due to pregnancy, the studies conducted showed that pregnancy has no negative effect on breast cancer prognosis. In this review we search for the frequency of breast cancer during pregnancy, the histopathological findings, risk factor, diagnostic and treatment modalities. We reviewed the literature for evidence based findings to help consult the patients on the outcome of breast cancer diagnosed during pregnancy and lactation, and also inform the patients who desire to become pregnant after breast cancer according to current evidences. PMID:24592003

  16. Affluence and Breast Cancer.

    Science.gov (United States)

    Lehrer, Steven; Green, Sheryl; Rosenzweig, Kenneth E

    2016-09-01

    High income, high socioeconomic status, and affluence increase breast cancer incidence. Socioeconomic status in USA breast cancer studies has been assessed by block-group socioeconomic measures. A block group is a portion of a census tract with boundaries that segregate, as far as possible, socioeconomic groups. In this study, we used US Census income data instead of block groups to gauge socioeconomic status of breast cancer patients in relationship with incidence, prognostic markers, and survival. US state breast cancer incidence and mortality data are from the U.S. Cancer Statistics Working Group, United States Cancer Statistics: 1999-2011. Three-Year-Average Median Household Income by State, 2010 to 2012, is from the U.S. Census Bureau, Current Population Survey, 2011 to 2013 Annual Social and Economic Supplements. County incomes are from the 2005-2009 American Community Survey of the U.S. Census Bureau. The American Community Survey is an ongoing statistical survey that samples a small percentage of the population yearly. Its purpose is to provide communities the information they need to plan investments and services. Breast cancer county incidence and survival data are from the National Cancer Institute's Surveillance, Epidemiology and End Results Program (SEER) data base. We analyzed SEER data from 198 counties in California, Connecticut, Georgia, Hawaii, Iowa, New Mexico, Utah, and Washington. SEER uses the Collaborative Stage (CS) Data Collection System. We have retained the SEER CS variables. There was a significant relationship of income with breast cancer incidence in 50 USA states and the District of Columbia in White women (r = 0.623, p breast cancer. Income was not correlated with 5-year survival of Black race (p = 0.364) or other races (p = 0.624). The multivariate general linear model with income as covariate, 5-year survival by race as a dependent variable, showed a significant effect of income and White race on 5-year survival (p breast cancer

  17. Hereditary breast cancer

    DEFF Research Database (Denmark)

    Larsen, Martin J; Thomassen, Mads; Gerdes, Anne-Marie

    2014-01-01

    Pathogenic mutations in BRCA1 or BRCA2 are only detected in 25% of families with a strong history of breast cancer, though hereditary factors are expected to be involved in the remaining families with no recognized mutation. Molecular characterization is expected to provide new insight...... into the tumor biology to guide the search of new high-risk alleles and provide better classification of the growing number of BRCA1/2 variants of unknown significance (VUS). In this review, we provide an overview of hereditary breast cancer, its genetic background, and clinical implications, before focusing...... on the pathologically and molecular features associated with the disease. Recent transcriptome and genome profiling studies of tumor series from BRCA1/2 mutation carriers as well as familial non-BRCA1/2 will be discussed. Special attention is paid to its association with molecular breast cancer subtypes as well...

  18. Breast cancer in systemic lupus

    DEFF Research Database (Denmark)

    Bernatsky, S.; Ramsey-Goldman, R.; Petri, M.

    2017-01-01

    Objective There is a decreased breast cancer risk in systemic lupus erythematosus (SLE) versus the general population. We assessed a large sample of SLE patients, evaluating demographic and clinical characteristics and breast cancer risk. Methods We performed case-cohort analyses within a multi......-center international SLE sample. We calculated the breast cancer hazard ratio (HR) in female SLE patients, relative to demographics, reproductive history, family history of breast cancer, and time-dependent measures of anti-dsDNA positivity, cumulative disease activity, and drugs, adjusted for SLE duration. Results...... There were 86 SLE breast cancers and 4498 female SLE cancer-free controls. Patients were followed on average for 7.6 years. Versus controls, SLE breast cancer cases tended to be white and older. Breast cancer cases were similar to controls regarding anti-dsDNA positivity, disease activity, and most drug...

  19. Quantitative imaging as cancer biomarker

    Science.gov (United States)

    Mankoff, David A.

    2015-03-01

    The ability to assay tumor biologic features and the impact of drugs on tumor biology is fundamental to drug development. Advances in our ability to measure genomics, gene expression, protein expression, and cellular biology have led to a host of new targets for anticancer drug therapy. In translating new drugs into clinical trials and clinical practice, these same assays serve to identify patients most likely to benefit from specific anticancer treatments. As cancer therapy becomes more individualized and targeted, there is an increasing need to characterize tumors and identify therapeutic targets to select therapy most likely to be successful in treating the individual patient's cancer. Thus far assays to identify cancer therapeutic targets or anticancer drug pharmacodynamics have been based upon in vitro assay of tissue or blood samples. Advances in molecular imaging, particularly PET, have led to the ability to perform quantitative non-invasive molecular assays. Imaging has traditionally relied on structural and anatomic features to detect cancer and determine its extent. More recently, imaging has expanded to include the ability to image regional biochemistry and molecular biology, often termed molecular imaging. Molecular imaging can be considered an in vivo assay technique, capable of measuring regional tumor biology without perturbing it. This makes molecular imaging a unique tool for cancer drug development, complementary to traditional assay methods, and a potentially powerful method for guiding targeted therapy in clinical trials and clinical practice. The ability to quantify, in absolute measures, regional in vivo biologic parameters strongly supports the use of molecular imaging as a tool to guide therapy. This review summarizes current and future applications of quantitative molecular imaging as a biomarker for cancer therapy, including the use of imaging to (1) identify patients whose tumors express a specific therapeutic target; (2) determine

  20. Prognostication in young and elderly breast cancer patients

    NARCIS (Netherlands)

    Kruijff, Esther Michelle de

    2015-01-01

    Part I describes the prognostic effect and interactions of the immune system in breast cancer patients. Part II of the thesis describes the prognostic effect of these prognostic immune parameters and biomarkers molecular subtypes and stem cell marker ALDH-1, which are known to be strong breast

  1. Signal enhancement ratio (SER) quantified from breast DCE-MRI and breast cancer risk

    Science.gov (United States)

    Wu, Shandong; Kurland, Brenda F.; Berg, Wendie A.; Zuley, Margarita L.; Jankowitz, Rachel C.; Sumkin, Jules; Gur, David

    2015-03-01

    Breast magnetic resonance imaging (MRI) is recommended as an adjunct to mammography for women who are considered at elevated risk of developing breast cancer. As a key component of breast MRI, dynamic contrast-enhanced MRI (DCE-MRI) uses a contrast agent to provide high intensity contrast between breast tissues, making it sensitive to tissue composition and vascularity. Breast DCE-MRI characterizes certain physiologic properties of breast tissue that are potentially related to breast cancer risk. Studies have shown that increased background parenchymal enhancement (BPE), which is the contrast enhancement occurring in normal cancer-unaffected breast tissues in post-contrast sequences, predicts increased breast cancer risk. Signal enhancement ratio (SER) computed from pre-contrast and post-contrast sequences in DCE-MRI measures change in signal intensity due to contrast uptake over time and is a measure of contrast enhancement kinetics. SER quantified in breast tumor has been shown potential as a biomarker for characterizing tumor response to treatments. In this work we investigated the relationship between quantitative measures of SER and breast cancer risk. A pilot retrospective case-control study was performed using a cohort of 102 women, consisting of 51 women who had diagnosed with unilateral breast cancer and 51 matched controls (by age and MRI date) with a unilateral biopsy-proven benign lesion. SER was quantified using fully-automated computerized algorithms and three SER-derived quantitative volume measures were compared between the cancer cases and controls using logistic regression analysis. Our preliminary results showed that SER is associated with breast cancer risk, after adjustment for the Breast Imaging Reporting and Data System (BI-RADS)-based mammographic breast density measures. This pilot study indicated that SER has potential for use as a risk factor for breast cancer risk assessment in women at elevated risk of developing breast cancer.

  2. Imaging biomarker roadmap for cancer studies

    NARCIS (Netherlands)

    O'Connor, James P. B.; Aboagye, Eric O.; Adams, Judith E.; Aerts, Hugo J. W. L.; Barrington, Sally F.; Beer, Ambros J.; Boellaard, Ronald; Bohndiek, Sarah E.; Brady, Michael; Brown, Gina; Buckley, David L.; Chenevert, Thomas L.; Clarke, Laurence P.; Collette, Sandra; Cook, Gary J.; Desouza, Nandita M.; Dickson, John C.; Dive, Caroline; Evelhoch, Jeffrey L.; Faivre-Finn, Corinne; Gallagher, Ferdia A.; Gilbert, Fiona J.; Gillies, Robert J.; Goh, Vicky; Griffiths, J. R.; Groves, Ashley M.; Halligan, Steve; Harris, Adrian L.; Hawkes, David J.; Hoekstra, Otto S.; Huang, Erich P.; Hutton, Brian F.; Jackson, Edward F.; Jayson, Gordon C.; Jones, Andrew; Koh, Dow-Mu; Lacombe, Denis; Lambin, Philippe; Lassau, Nathalie; Leach, Martin O.; Lee, Ting-Yim; Leen, Edward L.; Lewis, Jason S.; Liu, Yan; Lythgoe, Mark F.; Manoharan, Prakash; Maxwell, Ross J.; Miles, Kenneth A.; Morgan, Bruno; Morris, Steve; Ng, Tony; Padhani, Anwar R.; Parker, Geoff J. M.; Partridge, Mike; Pathak, Arvind P.; Peet, Andrew C.; Punwani, Shonit; Reynolds, Andrew R.; Robinson, Simon P.; Shankar, Lalitha K.; Sharma, Ricky A.; Soloviev, Dmitry; Stroobants, Sigrid G.; Sullivan, Daniel C.; Taylor, Stuart A.; Tofts, Paul S.; Tozer, Gillian M.; van Herk, Marcel B.; Walker-Samuel, Simon; Wason, James; Williams, Kaye J.; Workman, Paul; Yankeelov, Thomas E.; Brindle, Kevin M.; McShane, Lisa M.; Jackson, Alan; Waterton, John C.

    Imaging biomarkers (IBs) are integral to the routine management of patients with cancer. IBs used daily in oncology include clinical TNM stage, objective response and left ventricular ejection fraction. Other CT, MRI, PET and ultrasonography biomarkers are used extensively in cancer research and

  3. Pathology of hereditary breast cancer

    OpenAIRE

    van der Groep, Petra; van der Wall, Elsken; van Diest, Paul J.

    2011-01-01

    Background Hereditary breast cancer runs in families where several members in different generations are affected. Most of these breast cancers are caused by mutations in the high penetrance genes BRCA1 and BRCA2 accounting for about 5% of all breast cancers. Other genes that include CHEK2, PTEN, TP53, ATM, STK11/LKB1, CDH1, NBS1, RAD50, BRIP1 and PALB2 have been described to be high or moderate penetrance breast cancer susceptibility genes, all contributing to the hereditary breast cancer spe...

  4. Pregnancy-associated Breast Cancer.

    Science.gov (United States)

    Case, Ashley S

    2016-12-01

    Breast cancer is one of the most common malignancies affecting pregnancy. Pregnancy-associated breast cancer refers to breast cancer that is diagnosed during pregnancy or within the first postpartum year. The incidence is increasing as more women delay childbearing. Breast cancer can be safely diagnosed, staged, and treated during pregnancy while protecting the fetus and mother with excellent outcomes for both. Avoiding diagnostic delays is vital to prognosis. This article provides an overview of the diagnosis, staging, management, and prognosis of pregnancy-associated breast cancer. Relevant current literature is reviewed.

  5. Serum Human Epidermal Growth Factor 2 Extracellular Domain as a Predictive Biomarker for Lapatinib Treatment Efficacy in Patients With Advanced Breast Cancer.

    Science.gov (United States)

    Lee, Chee Khoon; Davies, Lucy; Gebski, Val J; Lord, Sarah J; Di Leo, Angelo; Johnston, Stephen; Geyer, Charles; Cameron, David; Press, Michael F; Ellis, Catherine; Loi, Sherene; Marschner, Ian; Simes, John; de Souza, Paul

    2016-03-20

    We examined the prognostic and predictive value of serum human epidermal growth factor 2 (HER2) extracellular domain (sHER2) in patients with advanced breast cancer treated with lapatinib using data from three randomized trials. We analyzed sHER2 and tissue HER2 (tHER2) data from 1,902 patients (84%) who were randomly assigned to receive lapatinib or control in the trials EGF30001, EGF30008, and EGF100151. Cox regression analyses were performed to correlate both biomarkers with progression-free survival (PFS) and overall survival (OS). Median sHER2 levels were 25.1 and 10.1 ng/mL in tHER2-amplified (tHER-positive) and nonamplified (tHER-negative) populations, respectively (r = 0.42 for sHER2-tHER2 correlation). Lapatinib had significant PFS benefit over control (hazard ratio [HR], 0.855; P = .004), but not OS (HR, 0.941; P = .33). Lapatinib PFS benefit is independently predicted by higher sHER2 values (HR per 10-ng/mL increase in sHER2: lapatinib-containing therapies, 1.009 v nonlapatinib-containing therapies, 1.044; P(interaction) < .001) and by positive tHER2 (HR [lapatinib v nonlapatinib]: tHER2 positive, 0.638 v tHER2 negative, 0.940; P(interaction) = .001). Within the tHER2-positive subpopulation (n = 515), higher sHER2 values still independently predicted lapatinib PFS benefit (HR per 10-ng/mL increase in sHER2: lapatinib-containing therapies, 1.017 v nonlapatinib-containing therapies, 1.041; P(interaction) = .008). In control arms (n = 936), higher sHER2 was associated with worse prognosis in multivariable analyses (PFS HR per 10 ng/mL: PFS, 1.024; P < .001; and OS, 1.018; P < .001). Higher sHER2 predicts greater PFS benefit with lapatinib independent of tHER2 status. High sHER2 is also independently prognostic for worse survival in patients who received nonlapatinib-containing therapies. The predictive role of sHER2 for other anti-HER2 agents requires further research. © 2016 by American Society of Clinical Oncology.

  6. Abortion, Miscarriage, and Breast Cancer Risk

    Science.gov (United States)

    ... of Breast & Gynecologic Cancers Breast Cancer Screening Research Abortion, Miscarriage, and Breast Cancer Risk: 2003 Workshop In ... cancer risk, including studies of induced and spontaneous abortions. They concluded that having an abortion or miscarriage ...

  7. Accelerated Radiation Therapy After Surgery in Treating Patients With Breast Cancer

    Science.gov (United States)

    2017-11-15

    Inflammatory Breast Cancer; Invasive Ductal Breast Carcinoma; Invasive Lobular Breast Carcinoma; Mucinous Ductal Breast Carcinoma; Papillary Ductal Breast Carcinoma; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Tubular Ductal Breast Carcinoma

  8. Does Aluminium Trigger Breast Cancer?

    OpenAIRE

    Peter Jennrich; Claus Schulte-Uebbing

    2016-01-01

    Summary. Breast cancer is by far the most common cancer in women in the western world. In 90% of breast cancers, environmental factors are among the causes. The frequency with which the tumour occurs in the outer upper part of the breast has risen with above average rates in recent decades. Aluminium salts as ingredients in deodorants and antiperspirants are being absorbed by the body to a greater extent than hitherto assumed. Their toxicity for healthy and diseased breast tissue cells includ...

  9. Cervical cancer: Biomarkers for diagnosis and treatment.

    Science.gov (United States)

    Dasari, Subramanyam; Wudayagiri, Rajendra; Valluru, Lokanatha

    2015-05-20

    Cervical cancer is a major gynecological cancer which involves uncontrolled cell division and tissue invasiveness of the female uterine cervix. With the availability of new technologies researchers have increased their efforts to develop novel biomarkers for early diagnosis, and evaluation and monitoring of therapeutic treatments. This approach will help in the development of early diagnosis and in increasing treatment efficacy with decreased recurrence. The present review explains the currently available biomarkers for cervical cancer diagnosis and prognosis. Apart from the currently available biomarkers the review also explains strategies for the development of biomarkers based on cellular and molecular approaches such as DNA, protein and other metabolic markers with suitable clinical examples. The investigations of specific proteins, enzymes and metabolites will establish more useful biomarkers for accurate detection and management of gynecological cancers especially cervical cancer. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Breast Cancer Survival Defined by the ER/PR/HER2 Subtypes and a Surrogate Classification according to Tumor Grade and Immunohistochemical Biomarkers

    Directory of Open Access Journals (Sweden)

    Carol A. Parise

    2014-01-01

    Full Text Available Introduction. ER, PR, and HER2 are routinely available in breast cancer specimens. The purpose of this study is to contrast breast cancer-specific survival for the eight ER/PR/HER2 subtypes with survival of an immunohistochemical surrogate for the molecular subtype based on the ER/PR/HER2 subtypes and tumor grade. Methods. We identified 123,780 cases of stages 1–3 primary female invasive breast cancer from California Cancer Registry. The surrogate classification was derived using ER/PR/HER2 and tumor grade. Kaplan-Meier survival analysis and Cox proportional hazards modeling were used to assess differences in survival and risk of mortality for the ER/PR/HER2 subtypes and surrogate classification within each stage. Results. The luminal B/HER2− surrogate classification had a higher risk of mortality than the luminal B/HER2+ for all stages of disease. There was no difference in risk of mortality between the ER+/PR+/HER2− and ER+/PR+/HER2+ in stage 3. With one exception in stage 3, the ER-negative subtypes all had an increased risk of mortality when compared with the ER-positive subtypes. Conclusions. Assessment of survival using ER/PR/HER2 illustrates the heterogeneity of HER2+ subtypes. The surrogate classification provides clear separation in survival and adjusted mortality but underestimates the wide variability within the subtypes that make up the classification.

  11. Pertuzumab, Trastuzumab, and Paclitaxel Albumin-Stabilized Nanoparticle Formulation in Treating Patients With HER2-Positive Advanced Breast Cancer

    Science.gov (United States)

    2017-09-08

    HER2-positive Breast Cancer; Recurrent Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer; Breast Adenocarcinoma; Inflammatory Breast Carcinoma

  12. Triple negative breast cancer: the role of metabolic pathways.

    Science.gov (United States)

    Dean, S J R; Rhodes, A

    2014-12-01

    The incidence of breast cancer in Malaysia and other Asian countries is on the increase, reflecting lifestyle changes some of which are known risk factors for the development of breast cancer. Most breast cancers are amenable to adjuvant therapies that target hormone receptors or HER2 receptors on the surface of the cancer cells and bring about significant improvement in survival. However, approximately 17% of Malaysian women with breast cancer, present with tumours that are devoid of these receptors and are consequently termed 'triple negative' breast cancers. These triple negative breast cancers typically occur in women of a younger age than receptor positive cancers, are predominantly of high grade tumours and the prognosis is usually poor. There is therefore a pressing need to understand the biological pathways that drive these tumours, in order that effective strategies are developed to treat these aggressive tumours. With the increasing affluence of developing countries, obesity and Type II Diabetes are also on the rise. These diseases are associated with an increased risk of developing a range of cancers including those of the breast. In particular, the metabolic syndrome has been shown to be associated with triple negative breast cancer. This article reviews some of the metabolic pathways and biomarkers which have been shown to be aberrantly expressed in triple negative breast cancer and highlights some of the ongoing work in this area.

  13. Breast Cancer - Early Diagnosis

    Centers for Disease Control (CDC) Podcasts

    2011-04-28

    This podcast answers a listener's question about how to tell if she has breast cancer.  Created: 4/28/2011 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 4/28/2011.

  14. Recurrent read-through fusion transcripts in breast cancer.

    Science.gov (United States)

    Varley, Katherine E; Gertz, Jason; Roberts, Brian S; Davis, Nicholas S; Bowling, Kevin M; Kirby, Marie K; Nesmith, Amy S; Oliver, Patsy G; Grizzle, William E; Forero, Andres; Buchsbaum, Donald J; LoBuglio, Albert F; Myers, Richard M

    2014-07-01

    Read-through fusion transcripts that result from the splicing of two adjacent genes in the same coding orientation are a recently discovered type of chimeric RNA. We sought to determine if read-through fusion transcripts exist in breast cancer. We performed paired-end RNA-seq of 168 breast samples, including 28 breast cancer cell lines, 42 triple negative breast cancer primary tumors, 42 estrogen receptor positive (ER+) breast cancer primary tumors, and 56 non-malignant breast tissue samples. We analyzed the sequencing data to identify breast cancer associated read-through fusion transcripts. We discovered two recurrent read-through fusion transcripts that were identified in breast cancer cell lines, confirmed across breast cancer primary tumors, and were not detected in normal tissues (SCNN1A-TNFRSF1A and CTSD-IFITM10). Both fusion transcripts use canonical splice sites to join the last splice donor of the 5' gene to the first splice acceptor of the 3' gene, creating an in-frame fusion transcript. Western blots indicated that the fusion transcripts are translated into fusion proteins in breast cancer cells. Custom small interfering RNAs targeting the CTSD-IFITM10 fusion junction reduced expression of the fusion transcript and reduced breast cancer cell proliferation. Read-through fusion transcripts between adjacent genes with different biochemical functions represent a new type of recurrent molecular defect in breast cancer that warrant further investigation as potential biomarkers and therapeutic targets. Both breast cancer associated fusion transcripts identified in this study involve membrane proteins (SCNN1A-TNFRSF1A and CTSD-IFITM10), which raises the possibility that they could be breast cancer-specific cell surface markers.

  15. Cytokines, Neovascularization and Breast Cancer

    Science.gov (United States)

    1996-10-01

    Rationale Angiogenesis is important in the growth and metastases of human breast cancer . We hypothesize that this process is under the control of...staining patern seen in invasive cancer , in situ cancer , and benign breast tissue. Note that staining was graded as the most intensly staining area. The...blocked, tumors do not grow or metastasize . The purpose of this study was to demonstrate that breast cancer cells are capable of participating in this

  16. Hormone therapy for breast cancer

    Science.gov (United States)

    ... of benefits: Taking Tamoxifen for 5 years after breast cancer surgery cuts the chance of cancer coming back by half. Some studies show that taking it for 10 years may work even better. It reduces the risk that cancer ...

  17. Opioids and breast cancer recurrence

    DEFF Research Database (Denmark)

    Cronin-Fenton, Deirdre P; Heide-Jørgensen, Uffe; Ahern, Thomas P

    2015-01-01

    BACKGROUND: Opioids may alter immune function, thereby potentially affecting cancer recurrence. The authors investigated the association between postdiagnosis opioid use and breast cancer recurrence. METHODS: Patients with incident, early stage breast cancer who were diagnosed during 1996 through...... 2008 in Denmark were identified from the Danish Breast Cancer Cooperative Group Registry. Opioid prescriptions were ascertained from the Danish National Prescription Registry. Follow-up began on the date of primary surgery for breast cancer and continued until breast cancer recurrence, death......, emigration, 10 years, or July 31, 2013, whichever occurred first. Cox regression models were used to compute hazard ratios and 95% confidence intervals associating breast cancer recurrence with opioid prescription use overall and by opioid type and strength, immunosuppressive effect, chronic use (≥6 months...

  18. Decision impact and feasibility of different ASCO-recommended biomarkers in early breast cancer: Prospective comparison of molecular marker EndoPredict and protein marker uPA/PAI-1.

    Directory of Open Access Journals (Sweden)

    Johannes Ettl

    Full Text Available Adjuvant therapy decisions in early breast cancer are based on accurate risk assessment. Urokinase plasminogen activator (uPA and plaminogen activator inhibitor-1 (PAI-1 have been the first biomarkers in hormone receptor (HR positive breast cancer to reach highest level of evidence. The EndoPredict test (EPclin combines gene expression information with nodal status and tumor size. The aim of this prospective study was to compare uPA/PAI-1 and EPclin as prognostic biomarkers with regard to feasibility, risk stratification and impact on adjuvant therapy recommendation.395 patients with HR positive, HER2 negative, intermediate risk breast cancer were enrolled. Relations and concordance of histologic grading as well as EPclin and uPA/PAI-1 values were assessed by Spearman's rank correlation coefficient and Cohen's Kappa. To compare decision impact of EPclin and uPA/PAI-1 three independent case discussions were held: One with known uPA/PAI-1 and EPclin results, one blinded to EPclin alone and another one blinded to both EPclin and uPA/PAI-1.EPclin could be determined in all 395 (100%, uPA/PAI-1 in 190 (48% of the tumor samples. EPclin allocated 250 patients (63% to the low-risk group and 145 patients (37% to the high-risk group, whereas uPA/PAI-1 allocated 88 patients (46% to the low-risk group and 102 patients (54% to the high-risk group. In 59% of cases, both tests showed concordant results. EPclin resulted more frequently in a change of therapy recommendation than the uPA/PAI-1 test (46% vs 24%. Recommendation of adjuvant chemotherapy (CTX was abandoned twice as often by EPclin (45% compared to uPA/PAI-1 (22%.In this first prospective comparison of EPclin and uPA/PAI-1 we found, that EPclin is superior to uPA/PAI-1 with respect to feasibility and decision impact. This leads to substantial avoidance of adjuvant CTX in endocrine-sensitive, HER2-negative breast cancer. Data collection for patients´ clinical outcome is ongoing.

  19. Prospective Biomarker Analysis of the Randomized CHER-LOB Study Evaluating the Dual Anti-HER2 Treatment With Trastuzumab and Lapatinib Plus Chemotherapy as Neoadjuvant Therapy for HER2-Positive Breast Cancer.

    Science.gov (United States)

    Guarneri, Valentina; Dieci, Maria Vittoria; Frassoldati, Antonio; Maiorana, Antonino; Ficarra, Guido; Bettelli, Stefania; Tagliafico, Enrico; Bicciato, Silvio; Generali, Daniele Giulio; Cagossi, Katia; Bisagni, Giancarlo; Sarti, Samanta; Musolino, Antonino; Ellis, Catherine; Crescenzo, Rocco; Conte, PierFranco

    2015-09-01

    The CHER-LOB randomized phase II study showed that the combination of lapatinib and trastuzumab plus chemotherapy increases the pathologic complete remission (pCR) rate compared with chemotherapy plus either trastuzumab or lapatinib. A biomarker program was prospectively planned to identify potential predictors of sensitivity to different treatments and to evaluate treatment effect on tumor biomarkers. Overall, 121 breast cancer patients positive for human epidermal growth factor 2 (HER2) were randomly assigned to neoadjuvant chemotherapy plus trastuzumab, lapatinib, or both trastuzumab and lapatinib. Pre- and post-treatment samples were centrally evaluated for HER2, p95-HER2, phosphorylated AKT (pAKT), phosphatase and tensin homolog, Ki67, apoptosis, and PIK3CA mutations. Fresh-frozen tissue samples were collected for genomic analyses. A mutation in PIK3CA exon 20 or 9 was documented in 20% of cases. Overall, the pCR rates were similar in PIK3CA wild-type and PIK3CA-mutated patients (33.3% vs. 22.7%; p = .323). For patients receiving trastuzumab plus lapatinib, the probability of pCR was higher in PIK3CA wild-type tumors (48.4% vs. 12.5%; p = .06). Ki67, pAKT, and apoptosis measured on the residual disease were significantly reduced from baseline. The degree of Ki67 inhibition was significantly higher in patients receiving the dual anti-HER2 blockade. The integrated analysis of gene expression and copy number data demonstrated that a 50-gene signature specifically predicted the lapatinib-induced pCR. PIK3CA mutations seem to identify patients who are less likely to benefit from dual anti-HER2 inhibition. p95-HER2 and markers of phosphoinositide 3-kinase pathway deregulation are not confirmed as markers of different sensitivity to trastuzumab or lapatinib. HER2 is currently the only validated marker to select breast cancer patients for anti-HER2 treatment; however, it is becoming evident that HER2-positive breast cancer is a heterogeneous disease. In addition, more

  20. Rapid biosensing tools for cancer biomarkers.

    Science.gov (United States)

    Ranjan, Rajeev; Esimbekova, Elena N; Kratasyuk, Valentina A

    2017-01-15

    The present review critically discusses the latest developments in the field of smart diagnostic systems for cancer biomarkers. A wide coverage of recent biosensing approaches involving aptamers, enzymes, DNA probes, fluorescent probes, interacting proteins and antibodies in vicinity to transducers such as electrochemical, optical and piezoelectric is presented. Recent advanced developments in biosensing approaches for cancer biomarker owes much credit to functionalized nanomaterials due to their unique opto-electronic properties and enhanced surface to volume ratio. Biosensing methods for a plenty of cancer biomarkers has been summarized emphasizing the key principles involved. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Breast-Conserving Surgery Followed by Radiation Therapy With MRI-Detected Stage I or Stage II Breast Cancer

    Science.gov (United States)

    2011-12-07

    Ductal Breast Carcinoma in Situ; Estrogen Receptor-negative Breast Cancer; Estrogen Receptor-positive Breast Cancer; HER2-negative Breast Cancer; HER2-positive Breast Cancer; Invasive Ductal Breast Carcinoma; Invasive Lobular Breast Carcinoma; Male Breast Cancer; Medullary Ductal Breast Carcinoma With Lymphocytic Infiltrate; Mucinous Ductal Breast Carcinoma; Papillary Ductal Breast Carcinoma; Progesterone Receptor-negative Breast Cancer; Progesterone Receptor-positive Breast Cancer; Stage I Breast Cancer; Stage II Breast Cancer; Tubular Ductal Breast Carcinoma

  2. Axillary Lymph Nodes and Breast Cancer

    Science.gov (United States)

    ... nodes . The axillary nodes are the first place breast cancer is likely to spread. During breast surgery, some ... if cancer cells are present. This helps determine breast cancer stage and guide treatment. So, it is more ...

  3. Breast cancer fear in African American breast cancer survivors.

    Science.gov (United States)

    Gibson, Lynette M; Thomas, Sheila; Parker, Veronica; Mayo, Rachel; Wetsel, Margaret Ann

    2014-01-01

    The purpose of this study was to describe breast cancer fear according to phase of survivorship, determine whether breast cancer fear levels differed among survivorship phases, and determine the relationship between fear and age in African-American breast cancer survivors. The study utilized secondary data analysis from the study, Inner Resources as Predictors of Psychological Well-Being in AABCS. A new subscale entitled, "Breast Cancer Fear" was adapted from the Psychological Well Being Subscale by Ferrell and Grant. There was no significant difference between fear and phase of survivorship. There was a significant positive relationship between age and fear.

  4. Body fatness, related biomarkers and cancer risk: an epidemiological perspective.

    Science.gov (United States)

    Nimptsch, Katharina; Pischon, Tobias

    2015-05-01

    Higher body fatness is not only associated with a higher risk of hypertension, type 2 diabetes, and coronary heart disease but also with certain types of cancer. The scope of this review is to summarize the epidemiological evidence for an association between body fatness and specific types of cancer and to outline the mediating role of obesity-related biomarkers in this context. Epidemiological studies have gathered convincing evidence that greater body fatness is associated with a higher risk of colorectal cancer, postmenopausal breast cancer, endometrial cancer, esophageal adenocarcinoma, renal cell carcinoma, and pancreatic cancer. Further, evidence for an association between higher body fatness and higher risk of ovarian cancer, advanced prostate cancer, and hepatocellular carcinoma is growing. Abdominal obesity is an independent risk factor for colorectal cancer beyond general obesity, whereas an independent role is less clear for other obesity-related cancer types. Epidemiological biomarker studies have shown that the positive association between body fatness and risk of cancer may be partly explained by hyperinsulinemia and altered concentrations in adipokines and sex-steroid hormones. In addition, obesity-associated low-grade inflammation plays a role in colorectal carcinogenesis. While epidemiology has contributed substantially to the understanding of the role of higher body fatness and related metabolic alterations in the development of cancer, further epidemiological biomarker studies are necessary to elucidate the complex interrelations between mediating pathways as well as to study novel pathways. Knowledge resulting from this research may help identify an obesity phenotype that is particularly strongly associated with cancer risk and thus pave the way for targeted prevention of cancer morbidity and mortality.

  5. Getting free of breast cancer

    DEFF Research Database (Denmark)

    Halttunen, Arja; Hietanen, P; Jallinoja, P

    1992-01-01

    Twenty-two breast cancer patients who were relapse-free and had no need for cancer-related treatment were interviewed 8 years after mastectomy in order to evaluate their feelings of getting free of breast cancer and the meaning of breast cancer in their lives. The study is a part of an intervention...... and follow-up study of 57 breast cancer patients. Half of the 22 patients still had frequent or occasional thoughts of recurrence and over two-thirds still thought they had not been 'cured' of cancer. More than half of the patients admitted that going through breast cancer had made them more mature. Women...... who had less thoughts of recurrence belonged to a group that had gone through an eight-week group psychotherapy intervention, were less depressed and had more other illnesses. Women who felt 'cured' had less limitations and restrictions due to cancer and belonged more often to higher social classes...

  6. Reproduction and Breast Cancer Risk

    Science.gov (United States)

    Hanf, Volker; Hanf, Dorothea

    2014-01-01

    Summary Reproduction is doubtlessly one of the main biological meanings of life. It is therefore not surprising that various aspects of reproduction impact on breast cancer risk. Various developmental levels may become targets of breast tumorigenesis. This review follows the chronologic sequence of events in the life of a female at risk, starting with the intrauterine development. Furthermore, the influence of both contraceptive measures and fertility treatment on breast cancer development is dealt with, as well as various pregnancy-associated factors, events, and perinatal outcomes. Finally, the contribution of breast feeding to a reduced breast cancer risk is discussed. PMID:25759622

  7. Molecular imaging of breast cancer

    NARCIS (Netherlands)

    Adams, A.L.L.

    2014-01-01

    Breast cancer is the most common type of cancer in women. Imaging techniques play a pivotal role in breast cancer management, especially in lesion detection, treatment planning and evaluation, and prognostication. These imaging techniques have however limitations such as the use of ionizing

  8. Proteomic profiling of mammary carcinomas identifies C7orf24, a gamma-glutamyl cyclotransferase, as a potential cancer biomarker

    DEFF Research Database (Denmark)

    Gromov, Pavel; Gromova, Irina; Friis, Esbern

    2010-01-01

    Breast cancer is the leading cause of cancer deaths in women today and is the most common cancer (excluding skin cancers) among women in the Western world. Although cancers detected by screening mammography are significantly smaller than nonscreening ones, noninvasive biomarkers for detection of ...

  9. Novel Approaches to Breast Cancer Prevention and Inhibition of Metastases

    Science.gov (United States)

    2015-10-01

    the ethnic population15. Tumors from BRCA1 mutation carriers are in general triple negative “basal” phenotype and thus have a bad prognosis and...biomarker for ER+ breast cancer and TSPAN6high expression defines a subpopulation of ER+ breast cancer patients with very good clinical prognosis. Thus...2009. 25. Reddy, B.V., and Irvine, K.D. (2008). The Fat and Warts signaling pathways: new insights into their regulation, mechanism and

  10. Efficacy of Neoadjuvant Cisplatin in Triple-Negative Breast Cancer

    DEFF Research Database (Denmark)

    Szallasi, Zoltan Imre; Eklund, Aron Charles; Li, Qiyuan

    2010-01-01

    share features suggesting common pathogenesis, we conducted a neoadjuvant trial of cisplatin in TNBC and explored specific biomarkers to identify predictors of response. PATIENTS AND METHODS Twenty-eight women with stage II or III breast cancers lacking estrogen and progesterone receptors and HER2/Neu...... (TNBC) were enrolled and treated with four cycles of cisplatin at 75 mg/m(2) every 21 days. After definitive surgery, patients received standard adjuvant chemotherapy and radiation therapy per their treating physicians. Clinical and pathologic treatment response were assessed, and pretreatment tumor......PURPOSE Cisplatin is a chemotherapeutic agent not used routinely for breast cancer treatment. As a DNA cross-linking agent, cisplatin may be effective treatment for hereditary BRCA1-mutated breast cancers. Because sporadic triple-negative breast cancer (TNBC) and BRCA1-associated breast cancer...

  11. Carboplatin treatment of antiestrogen-resistant breast cancer cells

    DEFF Research Database (Denmark)

    Larsen, Mathilde S; Yde, Christina Westmose; Christensen, Ib J

    2012-01-01

    Antiestrogen resistance is a major clinical problem in current breast cancer treatment. Therefore, biomarkers and new treatment options for antiestrogen-resistant breast cancer are needed. In this study, we investigated whether antiestrogen‑resistant breast cancer cell lines have increased...... to the antiestrogen tamoxifen, were more sensitive to carboplatin treatment compared to the parental MCF-7 cell line. This indicates that carboplatin may be an advantageous treatment in antiestrogen‑resistant breast cancer; however, a marker for increased sensitivity would be needed. Low Bcl-2 expression...... sensitivity to carboplatin, as it was previously shown with cisplatin, and whether low Bcl-2 expression levels have a potential value as marker for increased carboplatin sensitivity. Breast cancer cells resistant to the pure antiestrogen fulvestrant, and two out of four cell lines resistant...

  12. [Organized breast cancer screening].

    Science.gov (United States)

    Rouëssé, Jacques; Sancho-Garnier, Hélèn

    2014-02-01

    Breast screening programs are increasingly controversial, especially regarding two points: the number of breast cancer deaths they avoid, and the problem of over-diagnosis and over-treatment. The French national breast cancer screening program was extended to cover the whole country in 2004. Ten years later it is time to examine the risk/benefit ratio of this program and to discuss the need for change. Like all forms of cancer management, screening must be regularly updated, taking into account the state of the art, new evidence, and uncertainties. All screening providers should keep themselves informed of the latest findings. In the French program, women aged 50-74 with no major individual or familial risk factors for breast cancer are offered screening mammography and clinical breast examination every two years. Images considered non suspicious of malignancy by a first reader are re-examined by a second reader. The devices and procedures are subjected to quality controls. Participating radiologists (both public and private) are required to read at least 500 mammographies per year. The program's national participation rate was 52.7 % in 2012. When individual screening outside of the national program is taken into account (nearly 15 % of women), coverage appears close to the European recommendation of 65 %. Breast cancer mortality has been falling in France by 0.6 % per year for over 30 years, starting before mass screening was implemented, and by 1.5 % since 2005. This decline can be attributed in part to earlier diagnosis and better treatment, so that the specific impact of screening cannot easily be measured. Over-treatment, defined as the detection and treatment of low-malignancy tumors that would otherwise not have been detected in a person's lifetime, is a major negative effect of screening, but its frequency is not precisely known (reported to range from 1 % to 30 %). In view of these uncertainties, it would be advisable to modify the program in order to

  13. Inflammatory breast cancer in accessory abdominal breast tissue

    Directory of Open Access Journals (Sweden)

    Randy C. Miles, MD, MPH

    2017-12-01

    Full Text Available Accessory breast tissue results from failure of the embryologic mammary ridge, also known as the milk line, to involute. As a result, ectopic breast tissue can develop anywhere along this ridge, which extends from the axilla—the most common location—to the groin. Primary breast cancer in accessory breast tissue is uncommon but has been reported in multiple prior studies. We present a rare case of inflammatory breast cancer presenting in upper abdominal accessory breast tissue in women with a personal history of ipsilateral breast cancer, and highlight the challenges of both diagnosis and treatment of breast cancer in accessory breast tissue.

  14. Bisphosphonates for breast cancer.

    Science.gov (United States)

    Pavlakis, N; Schmidt, Rl; Stockler, M

    2005-07-20

    Bone is the most common site of metastatic disease associated with breast cancer affecting more than half of women during the course of their disease. Bone metastases are a significant cause of morbidity due to pain, pathological fractures, hypercalcaemia and spinal cord compression, and contribute to mortality. Bisphosphonates, which inhibit osteoclast-mediated bone resorption, are standard care for tumour-associated hypercalcaemia, and have been shown to reduce bone pain, improve quality of life, and to delay skeletal events and reduce their number in patients with multiple myeloma. Several randomized controlled trials have evaluated the role of bisphosphonates in breast cancer. To assess the effect of bisphosphonates on skeletal events, bone pain, quality of life and survival in women with early and advanced breast cancer. Randomized controlled trials were identified using the specialized register maintained by the Cochrane Breast Cancer Group (the search was applied to the databases Medline, Central/CCTR, Embase, CancerLit, and included handsearches from a number of other relevant sources). See: Cochrane Collaboration Collaborative Review Group in Breast Cancer search strategy. Randomized controlled trials evaluating skeletal events in women with metastatic breast cancer and early breast cancer comparing: 1. treatment with a bisphosphonate with the same treatment without a bisphosphonate 2. treatment with one bisphosphonate with treatment with a different bisphosphonate. Studies were selected by two independent reviewers. Studies fulfilling the eligibility criteria were evaluated for quality, particularly concealment of allocation to randomized groups. Data were extracted from the published papers or abstracts independently by the two primary reviewers for each of the specified endpoints (skeletal events, bone pain, quality of life and survival). Data on skeletal events and survival were presented as numbers of events, risk ratios and ratios of event rates

  15. Estrogens and breast cancer

    Directory of Open Access Journals (Sweden)

    HANKINSON SUSAN E

    1997-01-01

    Full Text Available In this review, we summarize the epidemiologic evidence for the associations of oral contraceptives and postmenopausal hormones with risk of breast cancer. We also describe the biologic plausibility of these relationships. Overall, there appears to be little, if any, increase in risk with oral contraceptive use in general, even among users for 10 or more years. However, compared to never users, current oral contraceptive users appear to have a modest elevation in risk that subsides within about 10 years after cessation of use. For postmenopausal hormones, the weight of the evidence suggests little or no increase in risk among users of short duration, or for use in the past. However, current longer term use is associated with an increased risk of breast cancer that increases with duration. This increase in risk is large enough, and well enough supported, to be considered along with the other risks and benefits of postmenopausal hormone therapy.

  16. Unemployment among breast cancer survivors.

    Science.gov (United States)

    Carlsen, Kathrine; Ewertz, Marianne; Dalton, Susanne Oksbjerg; Badsberg, Jens Henrik; Osler, Merete

    2014-05-01

    Though about 20% of working age breast cancer survivors do not return to work after treatment, few studies have addressed risk factors for unemployment. The majority of studies on occupational consequences of breast cancer focus on non-employment, which is a mixture of sickness absence, unemployment, retirement pensions and other reasons for not working. Unemployment in combination with breast cancer may represent a particular challenge for these women. The aim of the present study is therefore to analyze the risk for unemployment in the years following diagnosis and treatment for breast cancer. This study included 14,750 women diagnosed with breast cancer in Denmark 2001-2009 identified through a population-based clinical database and linked with information from Danish administrative population based registers for information on labour market affiliation, socio-demography and co-morbid conditions. Multivariable analyses were performed by Cox's proportional hazard models. Two years after treatment, 81% of patients were still part of the work force, 10% of which were unemployed. Increasing duration of unemployment before breast cancer was associated with an adjusted HR = 4.37 (95% CI: 3.90-4.90) for unemployment after breast cancer. Other risk factors for unemployment included low socioeconomic status and demography, while adjuvant therapy did not increase the risk of unemployment. Duration of unemployment before breast cancer was the most important determinant of unemployment after breast cancer treatment. This allows identification of a particularly vulnerable group of patients in need of rehabilitation.

  17. Proteomic classification of breast cancer.

    LENUS (Irish Health Repository)

    Kamel, Dalia

    2012-11-01

    Being a significant health problem that affects patients in various age groups, breast cancer has been extensively studied to date. Recently, molecular breast cancer classification has advanced significantly with the availability of genomic profiling technologies. Proteomic technologies have also advanced from traditional protein assays including enzyme-linked immunosorbent assay, immunoblotting and immunohistochemistry to more comprehensive approaches including mass spectrometry and reverse phase protein lysate arrays (RPPA). The purpose of this manuscript is to review the current protein markers that influence breast cancer prediction and prognosis and to focus on novel advances in proteomic classification of breast cancer.

  18. Imaging biomarker roadmap for cancer studies

    OpenAIRE

    O'Connor, JPB; Aboagye, EO; Adams, JE; Aerts, HJWL; Barrington, SF; Beer, AJ; Boellaard, R.; Bohndiek, SE; Brady, M.; Brown, G.; Buckley, DL; Chenevert, TL; Clarke, LP; Collette, S.; Cook, GJ

    2016-01-01

    Imaging biomarkers (IBs) are integral to the routine management of patients with cancer. IBs used daily in oncology include clinical TNM stage, objective response and left ventricular ejection fraction. Other CT, MRI, PET and ultrasonography biomarkers are used extensively in cancer research and drug development. New IBs need to be established either as useful tools for testing research hypotheses in clinical trials and research studies, or as clinical decision-making tools for use in healthc...

  19. Cancer statistics: Breast cancer in situ.

    Science.gov (United States)

    Ward, Elizabeth M; DeSantis, Carol E; Lin, Chun Chieh; Kramer, Joan L; Jemal, Ahmedin; Kohler, Betsy; Brawley, Otis W; Gansler, Ted

    2015-01-01

    An estimated 60,290 new cases of breast carcinoma in situ are expected to be diagnosed in 2015, and approximately 1 in 33 women is likely to receive an in situ breast cancer diagnosis in her lifetime. Although in situ breast cancers are relatively common, their clinical significance and optimal treatment are topics of uncertainty and concern for both patients and clinicians. In this article, the American Cancer Society provides information about occurrence and treatment patterns for the 2 major subtypes of in situ breast cancer in the United States-ductal carcinoma in situ and lobular carcinoma in situ-using data from the North American Association of Central Cancer Registries and the 13 oldest Surveillance, Epidemiology, and End Results registries. The authors also present an overview of in situ breast cancer detection, treatment, risk factors, and prevention and discuss research needs and initiatives. © 2015 American Cancer Society.

  20. A Randomized Controlled Trial of the Effects of Mindfulness-Based Stress Reduction (MBSR[BC]) on Levels of Inflammatory Biomarkers Among Recovering Breast Cancer Survivors.

    Science.gov (United States)

    Reich, Richard R; Lengacher, Cecile A; Klein, Thomas W; Newton, Cathy; Shivers, Steve; Ramesar, Sophia; Alinat, Carissa B; Paterson, Carly; Le, Alice; Park, Jong Y; Johnson-Mallard, Versie; Elias, Maya; Moscoso, Manolete; Goodman, Matthew; Kip, Kevin E

    2017-07-01

    The purpose of this substudy of a large randomized controlled trial was to evaluate the efficacy of the Mindfulness-Based Stress Reduction (Breast Cancer) (MBSR[BC]) program compared to usual care (UC) in normalizing blood levels of pro-inflammatory cytokines among breast cancer survivors (BCS). A total of 322 BCS were randomized to either a 6-week MBSR(BC) program or a UC. At baseline and 6 and 12 weeks, 10 ml of venous blood and demographic and clinical data were collected and/or updated. Plasma cytokines (interleukin [IL]-1β, IL-6, IL-10, tumor necrosis factor [TNF] α, transforming growth factor [TGF] β1, soluble tumor necrosis factor receptor [sTNFR] 1) were assayed. Linear mixed models were used to assess cytokine levels across three time points (baseline and 6 and 12 weeks) by group (MBSR[BC] vs. UC). Of the six measured cytokines, three were nondetectable at rates greater than 50% (IL-10, IL-1β, TGF-β1) and, because of overall low prevalence, were not analyzed further. For the remaining cytokines (TNFα, IL-6, sTNFR1), results showed that TNFα and IL-6 increased during the follow-up period (between 6 and 12 weeks) rather than during the MBSR(BC) training period (between baseline and 6 weeks), while sTNFR1 levels did not change significantly across the 12-week period. Study results suggest that MBSR(BC) affects cytokine levels in BCS, mainly with increases in TNFα and IL-6. The data further suggest that B-cell modulation may be a part of immune recovery during breast cancer management and that increases in TNFα and IL-6 may be markers for MBSR(BC)-related recovery.

  1. Breast cancer risk factors

    Directory of Open Access Journals (Sweden)

    Marzena Kamińska

    2015-09-01

    Full Text Available Breast cancer is the most frequently diagnosed neoplastic disease in women around menopause often leading to a significant reduction of these women’s ability to function normally in everyday life. The increased breast cancer incidence observed in epidemiological studies in a group of women actively participating in social and professional life implicates the necessity of conducting multidirectional studies in order to identify risk factors associated with the occurrence of this type of neoplasm. Taking the possibility of influencing the neoplastic transformation process in individuals as a criterion, all the risk factors initiating the process can be divided into two groups. The first group would include inherent factors such as age, sex, race, genetic makeup promoting familial occurrence of the neoplastic disease or the occurrence of benign proliferative lesions of the mammary gland. They all constitute independent parameters and do not undergo simple modification in the course of an individual’s life. The second group would include extrinsic factors conditioned by lifestyle, diet or long-term medical intervention such as using oral hormonal contraceptives or hormonal replacement therapy and their influence on the neoplastic process may be modified to a certain degree. Identification of modifiable factors may contribute to development of prevention strategies decreasing breast cancer incidence.

  2. Interleukin-19 in Breast Cancer

    Directory of Open Access Journals (Sweden)

    Ying-Yin Chen

    2013-01-01

    Full Text Available Inflammatory cytokines within the tumor microenvironment are linked to progression in breast cancer. Interleukin- (IL- 19, part of the IL-10 family, contributes to a range of diseases and disorders, such as asthma, endotoxic shock, uremia, psoriasis, and rheumatoid arthritis. IL-19 is expressed in several types of tumor cells, especially in squamous cell carcinoma of the skin, tongue, esophagus, and lung and invasive duct carcinoma of the breast. In breast cancer, IL-19 expression is correlated with increased mitotic figures, advanced tumor stage, higher metastasis, and poor survival. The mechanisms of IL-19 in breast cancer have recently been explored both in vitro and in vivo. IL-19 has an autocrine effect in breast cancer cells. It directly promotes proliferation and migration and indirectly provides a microenvironment for tumor progression, which suggests that IL-19 is a prognostic marker in breast cancer and that antagonizing IL-19 may have therapeutic potential.

  3. Alterations in three biomarkers (estrogen receptor, progesterone receptor and human epidermal growth factor 2) and the Ki67 index between primary and metastatic breast cancer lesions.

    Science.gov (United States)

    Fujii, Kimihito; Watanabe, Rie; Ando, Takahito; Kousaka, Junko; Mouri, Yukako; Yoshida, Miwa; Imai, Tsuneo; Nakano, Shogo; Fukutomi, Takashi

    2017-12-01

    In recurrent breast cancer, the tumor phenotype, as assessed by estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor 2 (HER2) status, occasionally changes. This change, in addition to the Ki67 index were evaluated at sites of recurrence and the correlation between changes in tumor phenotype and survival were assessed in breast cancer patients. Comparisons in pathological parameters between primary and metastatic lesions were drawn between ER, PR, HER2, and the Ki67 index in 70 patients with recurrent breast cancer. The association between changes in tumor phenotype and patient survival was assessed. The hormone receptor status changed from positive, in the primary lesions, to negative, in the metastatic lesions in 19.8% (ER) and 39.5% (PR) of patients, respectively. Conversion from negative to positive status was confirmed in 27.2% (ER) and 31.2% (PR) of patients, respectively. A change in HER2 status from negative (primary lesion) to positive (metastatic lesion) occurred in seven patients (10%). The mean Ki67 index of primary lesions with positive hormone receptor status was significantly lower than at sites of recurrence with any hormone receptor status, from 10.9±9.8 standard deviation (SD) to 22.9±18.6 (P=0.031) and 12.2±10.5 SD to 27.4±20.9 (P=0.023), for ER and PR, respectively. The mean overall survival of patients with ER status conversion from positive to negative was 7.4±1.2 standard error (SE) years, and 14.8±1.4 SE years for patients who retained positive ER status (P=0.005, log-rank), with a hazard ratio of 3.44 (95% confidence interval, 1.36-8.33). This difference in survival based upon change in ER status was similarly observed in patients with PR status conversion in the same direction. Thus, ER and PR status conversion at the time of recurrence strongly impact survival, particularly if the change is from positive (primary lesion) to negative (metastatic lesion). Monitoring the biological behavior of breast

  4. Identification of heparin-binding EGF-like growth factor (HB-EGF as a biomarker for lysophosphatidic acid receptor type 1 (LPA1 activation in human breast and prostate cancers.

    Directory of Open Access Journals (Sweden)

    Marion David

    Full Text Available Lysophosphatidic acid (LPA is a natural bioactive lipid with growth factor-like functions due to activation of a series of six G protein-coupled receptors (LPA₁₋₆. LPA receptor type 1 (LPA₁ signaling influences the pathophysiology of many diseases including cancer, obesity, rheumatoid arthritis, as well as lung, liver and kidney fibrosis. Therefore, LPA₁ is an attractive therapeutic target. However, most mammalian cells co-express multiple LPA receptors whose co-activation impairs the validation of target inhibition in patients because of missing LPA receptor-specific biomarkers. LPA₁ is known to induce IL-6 and IL-8 secretion, as also do LPA₂ and LPA₃. In this work, we first determined the LPA induced early-gene expression profile in three unrelated human cancer cell lines expressing different patterns of LPA receptors (PC3: LPA₁,₂,₆; MDA-MB-231: LPA1,2; MCF-7: LPA₂,₆. Among the set of genes upregulated by LPA only in LPA₁-expressing cells, we validated by QPCR and ELISA that upregulation of heparin-binding EGF-like growth factor (HB-EGF was inhibited by LPA₁-₃ antagonists (Ki16425, Debio0719. Upregulation and downregulation of HB-EGF mRNA was confirmed in vitro in human MDA-B02 breast cancer cells stably overexpressing LPA₁ (MDA-B02/LPA₁ and downregulated for LPA₁ (MDA-B02/shLPA1, respectively. At a clinical level, we quantified the expression of LPA₁ and HB-EGF by QPCR in primary tumors of a cohort of 234 breast cancer patients and found a significantly higher expression of HB-EGF in breast tumors expressing high levels of LPA₁. We also generated human xenograph prostate tumors in mice injected with PC3 cells and found that a five-day treatment with Ki16425 significantly decreased both HB-EGF mRNA expression at the primary tumor site and circulating human HB-EGF concentrations in serum. All together our results demonstrate that HB-EGF is a new and relevant biomarker with potentially high value in

  5. Chemoprevention of Breast Cancer by Mimicking the Protective Effect of Early First Birth. Addendum

    Science.gov (United States)

    2013-03-01

    densities and breast cancer risk. Cancer Epidemiol Biomarkers Prev 1998;7:1133-44. 4. Bartow SA, Pathak DR, Mettler FA. Radiographic microcalcification ...AD_________________ Award Number: W81XWH-05-1-0390 TITLE: Chemoprevention of breast cancer by...REPORT TYPE Final addendum 3. DATES COVERED 2 May 2012 – 2 February 2013 4. TITLE AND SUBTITLE Chemoprevention of breast cancer by mimicking the

  6. Triple Negative Breast Cancer Team Project — EDRN Public Portal

    Science.gov (United States)

    Triple negative breast cancers (TNBC), comprise 15-20% of breast cancers, and are associated with later stage at diagnosis, increased mortality, and occur more frequently in younger women where mammographic screening is less reliable. TNBCs are more likely to be diagnosed by physical exam than by mammographic screening. There is an unmet clinical need for biomarkers for the early detection of TNBC. Here, we are proposing the development of a plasma-based biomarker panel for the routine screening of women over the age of 40 for TNBC that can be used to identify women for further imaging.

  7. Breast cancer statistics and markers

    Directory of Open Access Journals (Sweden)

    Mallika Siva Donepudi

    2014-01-01

    Full Text Available Breast cancer is one of the familiar diseases in women. Incidence and mortality due to cancer, particularly breast cancer has been increasing for last 50 years, even though there is a lacuna in the diagnosis of breast cancer at early stages. According to World Health Organization (WHO 2012 reports, breast cancer is the leading cause of death in women, accounting 23% of all cancer deaths. In Asia, one in every three women faces the risk of breast cancer in their lifetime as per reports of WHO 2012. Here, the review is been focused on different breast cancer markers, that is, tissue markers (hormone receptors, human epidermal growth factor-2, urokinase plasminogen activator, plasminogen activator inhibitor, p53 and cathepsin D, genetic markers (BRAC1 and 2 and gene expression microarray technique, etc., and serum markers (CA 15.3, BR 27.29, MCA, CA 549, carcinoembryonic antigen, oncoproteins, and cytokeratins used in present diagnosis, but none of the mentioned markers can diagnose breast cancer at an early stage. There is a disquieting need for the identification of best diagnosing marker, which can be able to diagnose even in early stage of breast carcinogenesis.

  8. Quantitative proteomics of breast tumors: Tissue quality assessment to clinical biomarkers.

    Science.gov (United States)

    Chen, Yi; Britton, David; Wood, Elizabeth R; Brantley, Stephen; Magliocco, Anthony; Pike, Ian; Koomen, John M

    2017-03-01

    Liquid chromatography-selected reaction monitoring mass spectrometry (LC-SRM) is not only a proven tool for clinical chemistry, but also a versatile method to enhance the capability to quantify biomarkers for tumor biology research. As the treatment of cancer continues to evolve, the ability to assess multiple biomarkers to assign cancer phenotypes based on the genetic background and the signaling of the individual tumor becomes paramount to our ability to treat the patient. In breast cancer, the American Society of Clinical Oncology has defined biomarkers for patient assessment to guide selection of therapy: estrogen receptor, progesterone receptor, and the HER2/Neu receptor tyrosine kinase; therefore, these proteins were selected for LC-SRM assay development. Detailed molecular characterization of these proteins is necessary for patient treatment, so expression and phosphorylation assays have been developed and applied. In addition, other LC-SRM assays were developed to further evaluate tumor biology (e.g. Ki-67 for proliferation and vimentin for tumor aggressiveness related to the epithelial-to-mesenchymal transition). These measurements combined with biomarkers for tissue quality and histological content are implemented in a three-tier multiplexed assay platform, which is translated from cell line models into frozen tumor tissues banked from breast cancer patients. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Paclitaxel Albumin-Stabilized Nanoparticle Formulation in Treating Older Patients With Locally Advanced or Metastatic Breast Cancer

    Science.gov (United States)

    2017-08-18

    Male Breast Cancer; Recurrent Breast Cancer; Stage IV Breast Cancer; Estrogen Receptor-negative Breast Cancer; Estrogen Receptor-positive Breast Cancer; HER2-negative Breast Cancer; HER2-positive Breast Cancer; Progesterone Receptor-negative Breast Cancer; Progesterone Receptor-positive Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Triple-negative Breast Cancer

  10. Biomarkers of HIV-associated Cancer

    Directory of Open Access Journals (Sweden)

    Brian Thabile Flepisi

    2014-01-01

    Full Text Available Cancer biomarkers have provided great opportunities for improving the management of cancer patients by enhancing the efficiency of early detection, diagnosis, and efficacy of treatment. Every cell type has a unique molecular signature, referred to as biomarkers, which are identifiable characteristics such as levels or activities of a myriad of genes, proteins, or other molecular features. Biomarkers can facilitate the molecular definition of cancer, provide information about the course of cancer, and predict response to chemotherapy. They offer the hope of early detection as well as tracking disease progression and recurrence. Current progress in the characterization of molecular genetics of HIV-associated cancers may form the basis for improved patient stratification and future targeted or individualized therapies. Biomarker use for cancer staging and personalization of therapy at the time of diagnosis could improve patient care. This review focuses on the relevance of biomarkers in the most common HIV-associated malignancies, namely, Kaposi sarcoma, non-Hodgkin's lymphoma, and invasive cervical cancer.

  11. Extracellular vesicles: An overview of biogenesis, function, and role in breast cancer.

    Science.gov (United States)

    Zha, Quan Bin; Yao, Yu Feng; Ren, Zhao Jun; Li, Xiu Juan; Tang, Jin Hai

    2017-02-01

    Extracellular vesicles have emerged as important mediators of intercellular communication and play an active role in cancer, including breast cancer. Despite limited studies, initial observations suggest that these vesicles are important in breast physiology and pathophysiology. We here, in brief, describe their potential use as future biomarkers and therapeutic agents in breast cancer. Extracellular vesicles in blood and breast fluid may have a great potential to detect and predict the presence of breast cancer, and extracellular vesicles modulation may emerge as a therapeutic approach in cancer therapy.

  12. Use of Autoantibodies to Detect the Onset of Breast Cancer

    Directory of Open Access Journals (Sweden)

    Jérôme Lacombe

    2014-01-01

    Full Text Available The widespread use of screening mammography has resulted in increased detection of early-stage breast disease, particularly for in situ carcinoma and early-stage breast cancer. However, the majority of women with abnormalities noted on screening mammograms are not diagnosed with cancer because of several factors, including radiologist assessment, patient age, breast density, malpractice concerns, and quality control procedures. Although magnetic resonance imaging is a highly sensitive detection tool that has become standard for women at very high risk of developing breast cancer, it lacks sufficient specificity and costeffectiveness for use as a general screening tool. Therefore, there is an important need to improve screening and diagnosis of early-invasive and noninvasive tumors, that is, in situ carcinoma. The great potential for molecular tools to improve breast cancer outcomes based on early diagnosis has driven the search for diagnostic biomarkers. Identification of tumor-specific markers capable of eliciting an immune response in the early stages of tumor development seems to provide an effective approach for early diagnosis. The aim of this review is to describe several autoantibodies identified during breast cancer diagnosis. We will focus on these molecules highlighted in the past two years and discuss the potential future use of autoantibodies as biomarkers of early-stage breast cancer.

  13. Breast and Colon Cancer Family Registries

    Science.gov (United States)

    The Breast Cancer Family Registry and the Colon Cancer Family Registry were established by the National Cancer Institute as a resource for investigators to use in conducting studies on the genetics and molecular epidemiology of breast and colon cancer.

  14. Fulvestrant and/or Anastrozole in Treating Postmenopausal Patients With Stage II-III Breast Cancer Undergoing Surgery

    Science.gov (United States)

    2018-01-12

    Estrogen Receptor-positive Breast Cancer; HER2-negative Breast Cancer; Invasive Ductal Breast Carcinoma; Invasive Lobular Breast Carcinoma; Recurrent Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

  15. Breast Cancer Targeting Peptide Binds Keratin 1: A New Molecular Marker for Targeted Drug Delivery to Breast Cancer.

    Science.gov (United States)

    Soudy, Rania; Etayash, Hashem; Bahadorani, Kamran; Lavasanifar, Afsaneh; Kaur, Kamaljit

    2017-03-06

    The biomarkers or receptors expressed on cancer cells and the targeting ligands with high binding affinity for biomarkers play a key role in early detection and treatment of breast cancer. The breast cancer targeting peptide p160 (12-mer) and its enzymatically stable analogue 18-4 (10-mer) showed marked potential for breast cancer drug delivery using cell studies and animal models. Herein, we used affinity purification, liquid chromatography-tandem mass spectrometry, and proteomics to identify keratin 1 (KRT1) as the target receptor highly expressed on breast cancer cells for p160 peptide(s). Western blot and immunocytochemistry in MCF-7 breast cancer cells confirmed the identity of KRT1. We demonstrate that the p160 or 18-4 binding to MCF-7 breast cancer cells is dependent on the expression of KRT1, and we confirm peptide-KRT1 binding specificity using SPR experiments (Kd ∼ 1.1 μM and 0.98 μM for p160 and 18-4, respectively). Furthermore, we assessed the ability of peptide 18-4 to improve the cellular uptake and anticancer activity of a pro-apoptotic antimicrobial peptide, microcin J25 (MccJ25), in breast cancer cells. A covalent conjugate of peptide 18-4 with MccJ25 showed preferential cytotoxicity toward breast cancer cells with minimal cytotoxicity against normal HUVEC cells. The conjugate inhibited the growth of MDA-MB-435 MDR multidrug-resistant cells with an IC50 comparable to that of nonresistant cells. Conjugation improved selective cellular uptake of MccJ25, and the conjugate triggered cancer cell death by apoptosis. Our findings establish KRT1 as a new marker for breast cancer targeting. Additionally, it pinpoints the potential use of antimicrobial lasso peptides as a novel class of anticancer therapeutics.

  16. Breast cancer screening in Korean woman with dense breast tissue

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Hee Jung [Dept. of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul (Korea, Republic of); Ko, Eun Sook [Dept. of Radiology, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul (Korea, Republic of); Yi, Ann [Dept. of Radiology, Seoul National University College of Medicine, Seoul National University Hospital, Seoul (Korea, Republic of)

    2015-11-15

    Asian women, including Korean, have a relatively higher incidence of dense breast tissue, compared with western women. Dense breast tissue has a lower sensitivity for the detection of breast cancer and a higher relative risk for breast cancer, compared with fatty breast tissue. Thus, there were limitations in the mammographic screening for women with dense breast tissue, and many studies for the supplemental screening methods. This review included appropriate screening methods for Korean women with dense breasts. We also reviewed the application and limitation of supplemental screening methods, including breast ultrasound, digital breast tomosynthesis, and breast magnetic resonance imaging; and furthermore investigated the guidelines, as well as the study results.

  17. DNA Methylation Biomarkers: Cancer and Beyond

    Science.gov (United States)

    Mikeska, Thomas; Craig, Jeffrey M.

    2014-01-01

    Biomarkers are naturally-occurring characteristics by which a particular pathological process or disease can be identified or monitored. They can reflect past environmental exposures, predict disease onset or course, or determine a patient’s response to therapy. Epigenetic changes are such characteristics, with most epigenetic biomarkers discovered to date based on the epigenetic mark of DNA methylation. Many tissue types are suitable for the discovery of DNA methylation biomarkers including cell-based samples such as blood and tumor material and cell-free DNA samples such as plasma. DNA methylation biomarkers with diagnostic, prognostic and predictive power are already in clinical trials or in a clinical setting for cancer. Outside cancer, strong evidence that complex disease originates in early life is opening up exciting new avenues for the detection of DNA methylation biomarkers for adverse early life environment and for estimation of future disease risk. However, there are a number of limitations to overcome before such biomarkers reach the clinic. Nevertheless, DNA methylation biomarkers have great potential to contribute to personalized medicine throughout life. We review the current state of play for DNA methylation biomarkers, discuss the barriers that must be crossed on the way to implementation in a clinical setting, and predict their future use for human disease. PMID:25229548

  18. DNA Methylation Biomarkers: Cancer and Beyond

    Directory of Open Access Journals (Sweden)

    Thomas Mikeska

    2014-09-01

    Full Text Available Biomarkers are naturally-occurring characteristics by which a particular pathological process or disease can be identified or monitored. They can reflect past environmental exposures, predict disease onset or course, or determine a patient’s response to therapy. Epigenetic changes are such characteristics, with most epigenetic biomarkers discovered to date based on the epigenetic mark of DNA methylation. Many tissue types are suitable for the discovery of DNA methylation biomarkers including cell-based samples such as blood and tumor material and cell-free DNA samples such as plasma. DNA methylation biomarkers with diagnostic, prognostic and predictive power are already in clinical trials or in a clinical setting for cancer. Outside cancer, strong evidence that complex disease originates in early life is opening up exciting new avenues for the detection of DNA methylation biomarkers for adverse early life environment and for estimation of future disease risk. However, there are a number of limitations to overcome before such biomarkers reach the clinic. Nevertheless, DNA methylation biomarkers have great potential to contribute to personalized medicine throughout life. We review the current state of play for DNA methylation biomarkers, discuss the barriers that must be crossed on the way to implementation in a clinical setting, and predict their future use for human disease.

  19. Hormones, Women and Breast Cancer

    Science.gov (United States)

    ... before age 12) or reached menopause late (after age 55). Breast cancer is more common among women who • Are older • ... 40. If you are at high risk for breast cancer, you should get an annual mammogram beginning at age 40. Talk with your provider about other screening ...

  20. Overdiagnosis in breast cancer screening

    DEFF Research Database (Denmark)

    Lynge, Elsebeth; Beau, Anna-Belle; Christiansen, Peer

    2017-01-01

    Overdiagnosis in breast cancer screening is an important issue. A recent study from Denmark concluded that one in three breast cancers diagnosed in screening areas in women aged 50-69 years were overdiagnosed. The purpose of this short communication was to disentangle the study's methodology...

  1. Danish Breast Cancer Cooperative Group

    DEFF Research Database (Denmark)

    Christiansen, Peer; Ejlertsen, Bent; Jensen, Maj-Britt

    2016-01-01

    AIM OF DATABASE: Danish Breast Cancer Cooperative Group (DBCG), with an associated database, was introduced as a nationwide multidisciplinary group in 1977 with the ultimate aim to improve the prognosis in breast cancer. Since then, the database has registered women diagnosed with primary invasive...

  2. Histopathological Types of Breast Cancer

    African Journals Online (AJOL)

    Morin”. On the average it represents the prevalence of breast cancer in southern part of Nigeria. The mean age of diagnosis of breast cancer in females in our series was 45.7 years. This age compares favourably With the mean age in other parts of Nigeria. In Calabar, South — South. Nigeria the mean age was found to be ...

  3. Do fatty breasts increase or decrease breast cancer risk?

    Science.gov (United States)

    Shepherd, John A; Kerlikowske, Karla

    2012-01-25

    Few studies have investigated the association of non-dense area or fatty breasts in conjunction with breast density and breast cancer risk. Two articles in a recent issue of Breast Cancer Research investigate the role of absolute non-dense breast area measured on mammograms and find conflicting results: one article finds that non-dense breast area has a modest positive association with breast cancer risk, whereas the other finds that non-dense breast area has a strong protective effect to reduce breast cancer risk. Understanding the interplay of body mass index, menopause status, and measurement of non-dense breast area would help to clarify the contribution of non-dense breast area to breast cancer risk.

  4. Decline in breast cancer mortality

    DEFF Research Database (Denmark)

    Njor, Sisse Helle; Schwartz, Walter; Blichert-Toft, Mogens

    2015-01-01

    OBJECTIVES: When estimating the decline in breast cancer mortality attributable to screening, the challenge is to provide valid comparison groups and to distinguish the screening effect from other effects. In Funen, Denmark, multidisciplinary breast cancer management teams started before screening...... was introduced; both activities came later in the rest of Denmark. Because Denmark had national protocols for breast cancer treatment, but hardly any opportunistic screening, Funen formed a "natural experiment", providing valid comparison groups and enabling the separation of the effect of screening from other...... factors. METHODS: Using Poisson regression we compared the observed breast cancer mortality rate in Funen after implementation of screening with the expected rate without screening. The latter was estimated from breast cancer mortality in the rest of Denmark controlled for historical differences between...

  5. Unemployment among breast cancer survivors

    DEFF Research Database (Denmark)

    Carlsen, Kathrine; Ewertz, Marianne; Dalton, Susanne Oksbjerg

    2014-01-01

    AIM: Though about 20% of working age breast cancer survivors do not return to work after treatment, few studies have addressed risk factors for unemployment. The majority of studies on occupational consequences of breast cancer focus on non-employment, which is a mixture of sickness absence......, unemployment, retirement pensions and other reasons for not working. Unemployment in combination with breast cancer may represent a particular challenge for these women. The aim of the present study is therefore to analyze the risk for unemployment in the years following diagnosis and treatment for breast...... cancer. METHOD: This study included 14,750 women diagnosed with breast cancer in Denmark 2001-2009 identified through a population-based clinical database and linked with information from Danish administrative population based registers for information on labour market affiliation, socio...

  6. Methylated genes as new cancer biomarkers

    DEFF Research Database (Denmark)

    Brunner, Nils; Duffy, M.J; Napieralski, R.

    2009-01-01

    that measurement of the methylation status of the promoter regions of specific genes can aid early detection of cancer, determine prognosis and predict therapy responses. Promising DNA methylation biomarkers include the use of methylated GSTP1 for aiding the early diagnosis of prostate cancer, methylated PITX2...

  7. Advances in Biomarker Research for Pancreatic Cancer

    Science.gov (United States)

    Bhat, Kruttika; Wang, Fengfei; Ma, Qingyong; Li, Qinyu; Mallik, Sanku; Hsieh, Tze-chen; Wu, Erxi

    2012-01-01

    Pancreatic cancer (PC) is a leading cause of cancer related deaths in United States. The lack of early symptoms results in late-stage detection and a high mortality rate. Currently, the only potentially curative approach for PC is surgical resection, which is often unsuccessful because the invasive and metastatic nature of the tumor masses makes their complete removal difficult. Consequently, patients suffer relapses from remaining cancer stem cells or drug resistance that eventually lead to death. To improve the survival rate, the early detection of PC is critical. Current biomarker research in PC indicates that a serum carbohydrate antigen, CA 19-9, is the only available biomarker with approximately 90% specificity to PC. However, the efficacy of CA 19-9 for assessing prognosis and monitoring patients with PC remains contentious. Thus, advances in technology and the detection of new biomarkers with high specificity to PC are needed to reduce the mortality rate of pancreatic cancer. PMID:22372502

  8. Pregnancy associated breast cancer and pregnancy after breast cancer treatment

    OpenAIRE

    Doğer, Emek; Çalışkan, Eray; Mallmann, Peter

    2011-01-01

    Breast cancer is one of the most common cancers diagnosed during pregnancy and its frequency is increasing as more women postpone their pregnancies to their thirties and forties. Breast cancer diagnosis during pregnancy and lactation is difficult and complex both for the patient and doctors. Delay in diagnosis is frequent and treatment modalities are difficult to accept for the pregnant women. The common treatment approach is surgery after diagnosis, chemotherapy after the first trimester and...

  9. Identification and prognostic value of anterior gradient protein 2 expression in breast cancer based on tissue microarray.

    Science.gov (United States)

    Guo, Jilong; Gong, Guohua; Zhang, Bin

    2017-07-01

    Breast cancer has attracted substantial attention as one of the major cancers causing death in women. It is crucial to find potential biomarkers of prognostic value in breast cancer. In this study, the expression pattern of anterior gradient protein 2 in breast cancer was identified based on the main molecular subgroups. Through analysis of 69 samples from the Gene Expression Omnibus database, we found that anterior gradient protein 2 expression was significantly higher in non-triple-negative breast cancer tissues compared with normal tissues and triple-negative breast cancer tissues (p Cancer Genome Atlas were analysed. The data from The Cancer Genome Atlas and results from quantitative reverse transcription polymerase chain reaction also verified the anterior gradient protein 2 expression pattern. Furthermore, we performed immunohistochemical analysis. The quantification results revealed that anterior gradient protein 2 is highly expressed in non-triple-negative breast cancer (grade 3 excluded) and grade 1 + 2 (triple-negative breast cancer excluded) tumours compared with normal tissues. Anterior gradient protein 2 was significantly highly expressed in non-triple-negative breast cancer (grade 3 excluded) and non-triple-negative breast cancer tissues compared with triple-negative breast cancer tissues (p breast cancer excluded) and grade 1 + 2 tissues compared with grade 3 tissues (p breast cancer and can be regarded as a putative biomarker for breast cancer prognosis.

  10. Genetic risk of breast cancer.

    Science.gov (United States)

    Nasir, A; Shackelford, R E; Anwar, F; Yeatman, T J

    2009-12-01

    Several cutting-edge strategies are being used to evaluate candidate genetic risk factors for breast cancer. These include linkage analysis for mapping out BRCA1 and BRCA2, mutational screening of candidate risk genes like CHEK2, ATM, BRIP1 and PALB2, which are associated with an intermediate level of breast cancer risk. Genome-wide association studies have revealed several low-penetrance breast cancer risk alleles. The predisposition factors are associated with different levels of breast cancer risk. Relative to control population, the risk in patients harboring high-risk BRCA1 and 2 mutations is over 10-fold, with intermediate penetrance genes 2 to 4-fold and with low penetrance alleles less than 1.5-fold. Overall, these factors account for about 25% of the genetic risk for breast cancer. In the remainder, genetic factors to contribute to the risk of breast cancer remain unknown and are a subject of current investigation. With discovery and validation of newer and clinically relevant predisposition factors, additional breast cancer risk categories may be recognized. BRCA1 and BRCA2 mutation testing allows identification of individuals at increased risk of breast cancer who are offered risk-reducing interventions. Targeted therapies are being developed that may refine management of patients with BRCA1 and BRCA2 mutations. Further genome-wide studies are required to identify clinically relevant molecular factors that will allow more accurate and widely applicable genetic risk stratification. Current efforts in discovery, validation and qualification of molecular markers of breast cancer risk offer considerable promise in the future to develop more accurate breast cancer risk assessment along with development of more effective chemopreventive and therapeutic strategies.

  11. Functional Magnetic Resonance Imaging in Assessing Affect Reactivity and Regulation in Patients With Stage 0-III Breast Cancer

    Science.gov (United States)

    2017-02-27

    Healthy Subject; Stage 0 Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

  12. Breast Tissue Composition and Susceptibility to Breast Cancer

    Science.gov (United States)

    Martin, Lisa J.; Bronskill, Michael; Yaffe, Martin J.; Duric, Neb; Minkin, Salomon

    2010-01-01

    Breast density, as assessed by mammography, reflects breast tissue composition. Breast epithelium and stroma attenuate x-rays more than fat and thus appear light on mammograms while fat appears dark. In this review, we provide an overview of selected areas of current knowledge about the relationship between breast density and susceptibility to breast cancer. We review the evidence that breast density is a risk factor for breast cancer, the histological and other risk factors that are associated with variations in breast density, and the biological plausibility of the associations with risk of breast cancer. We also discuss the potential for improved risk prediction that might be achieved by using alternative breast imaging methods, such as magnetic resonance or ultrasound. After adjustment for other risk factors, breast density is consistently associated with breast cancer risk, more strongly than most other risk factors for this disease, and extensive breast density may account for a substantial fraction of breast cancer. Breast density is associated with risk of all of the proliferative lesions that are thought to be precursors of breast cancer. Studies of twins have shown that breast density is a highly heritable quantitative trait. Associations between breast density and variations in breast histology, risk of proliferative breast lesions, and risk of breast cancer may be the result of exposures of breast tissue to both mitogens and mutagens. Characterization of breast density by mammography has several limitations, and the uses of breast density in risk prediction and breast cancer prevention may be improved by other methods of imaging, such as magnetic resonance or ultrasound tomography. PMID:20616353

  13. Exercise in Targeting Metabolic Dysregulation in Stage I-III Breast or Prostate Cancer Survivors

    Science.gov (United States)

    2017-09-12

    Cancer Survivor; No Evidence of Disease; Obesity; Overweight; Prostate Carcinoma; Sedentary Lifestyle; Stage I Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage III Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

  14. Exercise Intervention in Targeting Adiposity and Inflammation With Movement to Improve Prognosis in Breast Cancer

    Science.gov (United States)

    2017-12-18

    Cancer Survivor; Central Obesity; Estrogen Receptor Positive; Postmenopausal; Progesterone Receptor Positive; Stage I Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage III Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

  15. Raising an Antibody Specific to Breast Cancer Subpopulations Using Phage Display on Tissue Sections

    DEFF Research Database (Denmark)

    Larsen, Simon Asbjørn; Meldgaard, Theresa; Fridriksdottir, Agla Jael Rubner

    2016-01-01

    fragments specific against breast cancer subpopulations, aiding the discovery of novel biomarkers. MATERIALS AND METHODS: Recombinant antibody fragments were selected by phage display. A novel shadowstick technology enabled the direct selection using tissue sections of antibody fragments specific against......BACKGROUND/AIM: Primary tumors display a great level of intra-tumor heterogeneity in breast cancer. The current lack of prognostic and predictive biomarkers limits accurate stratification and the ability to predict response to therapy. The aim of the present study was to select recombinant antibody...... small subpopulations of breast cancer cells. Selections were performed against a subpopulation of breast cancer cells expressing CD271(+), as these previously have been indicated to be potential breast cancer stem cells. The selected antibody fragments were screened by phage ELISA on both breast cancer...

  16. Aluminium, antiperspirants and breast cancer.

    Science.gov (United States)

    Darbre, P D

    2005-09-01

    Aluminium salts are used as the active antiperspirant agent in underarm cosmetics, but the effects of widespread, long term and increasing use remain unknown, especially in relation to the breast, which is a local area of application. Clinical studies showing a disproportionately high incidence of breast cancer in the upper outer quadrant of the breast together with reports of genomic instability in outer quadrants of the breast provide supporting evidence for a role for locally applied cosmetic chemicals in the development of breast cancer. Aluminium is known to have a genotoxic profile, capable of causing both DNA alterations and epigenetic effects, and this would be consistent with a potential role in breast cancer if such effects occurred in breast cells. Oestrogen is a well established influence in breast cancer and its action, dependent on intracellular receptors which function as ligand-activated zinc finger transcription factors, suggests one possible point of interference from aluminium. Results reported here demonstrate that aluminium in the form of aluminium chloride or aluminium chlorhydrate can interfere with the function of oestrogen receptors of MCF7 human breast cancer cells both in terms of ligand binding and in terms of oestrogen-regulated reporter gene expression. This adds aluminium to the increasing list of metals capable of interfering with oestrogen action and termed metalloestrogens. Further studies are now needed to identify the molecular basis of this action, the longer term effects of aluminium exposure and whether aluminium can cause aberrations to other signalling pathways in breast cells. Given the wide exposure of the human population to antiperspirants, it will be important to establish dermal absorption in the local area of the breast and whether long term low level absorption could play a role in the increasing incidence of breast cancer.

  17. Impact of celecoxib on capecitabine tolerability and activity in pretreated metastatic breast cancer: results of a phase II study with biomarker evaluation.

    Science.gov (United States)

    Fabi, Alessandra; Metro, Giulio; Papaldo, Paola; Mottolese, Marcella; Melucci, Elisa; Carlini, Paolo; Sperduti, Isabella; Russillo, Michelangelo; Gelibter, Alain; Ferretti, Gianluigi; Tomao, Silverio; Milella, Michele; Cognetti, Francesco

    2008-09-01

    Preclinical evidence suggests that the cyclo-oxygenase-2 (COX-2) enzyme plays an important role in breast cancer progression. The aim of the present phase II study was to determine the activity and safety of the combination of the COX-2 inhibitor celecoxib with capecitabine in metastatic breast cancer (MBC) patients pretreated with anthracyclines and/or taxanes. Eligible patients received capecitabine 1,000 mg/m(2) twice daily on days 1-14 every 21 days and celecoxib 200 mg twice daily, continuously, until disease progression or unacceptable toxicity. About 42 pretreated MBC patients were enrolled into the study. Median number of previous chemotherapy lines for metastatic disease was 2 (0-3). Seven patients (19%) responded to treatment while disease stabilization occurred in 17 patients (40.5%). Overall, 20 patients (47.5%) achieved clinical benefit [objective responses (CR) plus stable disease (SD) >/=6 months]. Median time to progression (TTP) and median overall survival (OS) were 5.2 and 17.8 months, respectively. Treatment was very well tolerated: grade 3 toxicities were observed in only five patients, respectively, and no grade 4 adverse events were reported. Celecoxib was never discontinued for toxicity. Analysis of COX-2 expression in the 22 patients with available tissue revealed a significantly longer TTP and OS for patients whose tumors over-expressed COX-2. The combination of capecitabine and celecoxib is active and safe in far advanced MBC patients. Interestingly, this association resulted in a lower-than-expected toxicity, as compared to single-agent capecitabine. The clinical relevance of COX-2 as determinant of sensitivity to treatment with celecoxib should be further evaluated in larger series of patients.

  18. Having children after breast cancer.

    Science.gov (United States)

    Dow, K H

    1994-01-01

    Having children after breast cancer is an important clinical issue. Evidence from clinical studies on pregnancy subsequent to breast cancer has not shown a survival disadvantage. Clinical experience suggests that desire for children, support from family, and quality of life issues are also important factors in decisions about pregnancy. This qualitative study was done (1) to identify reasons why young women decide to become pregnant after breast cancer; (2) to describe concerns about subsequent pregnancy; (3) to describe helpful behaviors in decision making; and (4) to explore the meaning of having children after breast cancer. Twenty-three women were identified who had early-stage breast cancer and became pregnant after breast-conserving surgery and radiation therapy. Sixteen women participated in a semi-structured interview. Qualitative data were analyzed for content. Results indicate that pregnancy subsequent to breast cancer is a powerful stimulus for young women to "get well" again. Reasons for subsequent pregnancy were related to the women's developmental age. Young women expressed concerns about the potential for future disease recurrence, about breast self-examination and mammography during pregnancy, and about surviving to see their children grow up. Perceived helpful behaviors included developing a realistic perspective, living with uncertainty, love and support of spouse, and delineating differences between personal and medical decision making.

  19. Metformin in breast cancer - an evolving mystery.

    Science.gov (United States)

    Camacho, Laura; Dasgupta, Atreyi; Jiralerspong, Sao

    2015-06-26

    Metformin, a diabetes drug with well-established side effect and safety profiles, has been widely studied for its anti-tumor activities in a number of cancers, including breast cancer. But its mechanism of action in the clinical arena remains elusive. In a window of opportunity trial of metformin in non-diabetic breast cancer patients, Dowling and colleagues examined both the direct actions of the drug on cancer cells (as mediated by AMP kinase), as well as its indirect actions (as mediated by circulating insulin). The data suggest that short-term administration of metformin in this setting has anti-tumor effects significantly involving the indirect, insulin-dependent pathway. The role of the direct pathway remains to be determined. This study represents an important step forward in establishing one of several possible mechanisms for metformin, information that will be useful in determining candidate biomarkers to evaluate in large clinical trials of metformin, such as the ongoing NCIC CTG MA.32 trial of adjuvant metformin. The potential significance of these data for metformin in the treatment of breast cancer is discussed here.

  20. Dietary compared with blood concentrations of carotenoids and breast cancer risk: a systematic review and meta-analysis of prospective studies

    National Research Council Canada - National Science Library

    Aune, Dagfinn; Chan, Doris S M; Vieira, Ana Rita; Navarro Rosenblatt, Deborah A; Vieira, Rui; Greenwood, Darren C; Norat, Teresa

    2012-01-01

    .... Carotenoid concentrations in blood are biomarkers of fruit and vegetable intake; however, no systematic assessment has compared dietary intake with blood concentrations of carotenoids and breast cancer risk...

  1. Diet and breast cancer

    Directory of Open Access Journals (Sweden)

    Isabelle Romieu

    2011-10-01

    Full Text Available Both diet and nutrition have been studied in relationship with breast cancer risk, as the great variation among different countries in breast cancer incidence could possibly be explained through the inflammatory and immune response, as well as antioxidant intake, among others.To date, no clear association with diet beyond overweight and weight gain has been found, except for alcohol consumption. Nonetheless, the small number of studies done in middle to low income countries where variability of food intake is wider,is beginning to show interesting results.Tanto la dieta como la nutrición han sido estudiadas en relación con el riesgo de cáncer de mama, dada la gran variación de incidencia de cáncer entre países, y la posibilidad de explicarla a través de la respuesta inflamatoria o inmune, así como ingesta de antioxidantes,entre otros.Hasta la fecha, ninguna asociación clara con la dieta ha sido encontrada, excepto para el consumo de alcohol, más allá del sobrepeso y del incremento de peso. Sin embargo, los estudios que se están realizando en países de mediano a bajo nivel de ingresos, con mayor variabilidad de ingesta de alimentos, comienzan a mostrar resultados interesantes.

  2. Awareness of Breast Cancer and Breast Self Examination Among ...

    African Journals Online (AJOL)

    Background: Breast cancer is the commonest malignancy affecting women in Nigeria. Regular breast self examination reduces morbidity and mortality from this disease. Objective: To assess the knowledge of breast cancer, breast self examination and practice amongst secondary school teachers in Enugu , Nigeria.

  3. Mitosis Counting in Breast Cancer : Object-Level Interobserver Agreement and Comparison to an Automatic Method

    NARCIS (Netherlands)

    Veta, Mitko; van Diest, Paul J|info:eu-repo/dai/nl/075281775; Jiwa, Mehdi; Al-Janabi, Shaimaa; Pluim, JPW|info:eu-repo/dai/nl/224274333

    2016-01-01

    BACKGROUND: Tumor proliferation speed, most commonly assessed by counting of mitotic figures in histological slide preparations, is an important biomarker for breast cancer. Although mitosis counting is routinely performed by pathologists, it is a tedious and subjective task with poor

  4. Epigenetics in breast and prostate cancer.

    Science.gov (United States)

    Wu, Yanyuan; Sarkissyan, Marianna; Vadgama, Jaydutt V

    2015-01-01

    Most recent investigations into cancer etiology have identified a key role played by epigenetics. Specifically, aberrant DNA and histone modifications which silence tumor suppressor genes or promote oncogenes have been demonstrated in multiple cancer models. While the role of epigenetics in several solid tumor cancers such as colorectal cancer are well established, there is emerging evidence that epigenetics also plays a critical role in breast and prostate cancer. In breast cancer, DNA methylation profiles have been linked to hormone receptor status and tumor progression. Similarly in prostate cancer, epigenetic patterns have been associated with androgen receptor status and response to therapy. The regulation of key receptor pathways and activities which affect clinical therapy treatment options by epigenetics renders this field high priority for elucidating mechanisms and potential targets. A new set of methylation arrays are now available to screen epigenetic changes and provide the cutting-edge tools needed to perform such investigations. The role of nutritional interventions affecting epigenetic changes particularly holds promise. Ultimately, determining the causes and outcomes from epigenetic changes will inform translational applications for utilization as biomarkers for risk and prognosis as well as candidates for therapy.

  5. Breast Cancer: A preventable disease

    Directory of Open Access Journals (Sweden)

    Zoya Tahergorabi

    2014-08-01

    Full Text Available With regard to high cancer incidence, as one of the major mortality causes worldwide, following human societies industrialization in recent years breast cancer, dealt with in the present article, has got a particular impact on women who possess a pivotal role in family and society. Thus, adoption of effective diagnostic procedures in the early stages of the disease is very important, which must be considered as a substantial component of the strategies aimed at women’s health promotion and decreasing of breast cancer mortality rate. Meanwhile, women’s education and their awareness promotion and advising them to carry out different methods of breast cancer screening in the early stages of the symptoms, as preventive measures, play important roles. The present review article attempts to study prevalence and epidemiology of breast cancer, its risk factors and its different stages of prevention.

  6. VOC breath biomarkers in lung cancer.

    Science.gov (United States)

    Saalberg, Yannick; Wolff, Marcus

    2016-08-01

    This review provides an overview of volatile organic compounds (VOCs) which are considered lung cancer biomarkers for diagnostic breath analysis. It includes results of scientific publications from 1985 to 2015. The identified VOCs are listed and ranked according to their occurrence of nomination. The applied detection and sampling methods are specified but not evaluated. Possible reasons for the different results of the studies are stated. Among the most frequently emerging biomarkers are 2-butanone and 1-propanol as well as isoprene, ethylbenzene, styrene and hexanal. The outcome of this review may be helpful for the development of a lung cancer screening device. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. The Attenuation Distribution Across the Long Axis of Breast Cancer Liver Metastases at CT: A Quantitative Biomarker for Predicting Overall Survival.

    Science.gov (United States)

    Abramson, Richard G; Lakomkin, Nikita; Hainline, Allison; Kang, Hakmook; Hutson, M Shane; Arteaga, Carlos L

    2018-01-01

    The objective of our study was to compare attenuation distribution across the long-axis (ADLA) measurements, Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, and Choi criteria for predicting overall survival (OS) in patients with metastatic breast cancer treated with bevacizumab. We obtained HIPAA-compliant data from a prospective, multisite, phase 3 trial of bevacizumab for the treatment of metastatic breast cancer. For patients with one or more liver metastases measuring 15 mm or larger at baseline, we evaluated up to two target liver lesions using RECIST, Choi criteria, and ADLA measurements, with the latter defined as the SD of the CT attenuation values of each pixel along the tumor long-axis diameter. The optimal percentage change threshold for defining an ADLA response was computed by cross-validation analysis in a Cox model. The log-rank test was applied to evaluate RECIST, Choi criteria, and ADLA for discriminating patients with superior OS. The predictive accuracies of all three techniques were compared using Brier scores and areas under the ROC curve (AUC). All analyses were performed separately using best overall response (BOR) and response at the first follow-up time point (FU1). One hundred sixty-four patients met the inclusion criteria. A 25% decrease in the ADLA measurement from baseline was the optimal ADLA response threshold for BOR and FU1. RECIST, Choi criteria, and ADLA successfully identified patients with superior OS when using BOR (RECIST, p = 0.02; Choi and ADLA, p < 0.001), but only Choi criteria and ADLA measurements were successful when using FU1 (RECIST, p = 0.43; Choi and ADLA, p < 0.001). In a direct comparison, ADLA measurements outperformed both RECIST and Choi criteria using BOR (95% CI for Brier score differences, ADLA-RECIST [-0.58 to -0.08] and ADLA-Choi [-0.55 to -0.06]; 95% CI for AUC differences, ADLA-RECIST [0.16-0.33] and ADLA-Choi [0.17-0.36]) as well as using FU1 (95% CI for Brier score differences, ADLA

  8. Progress in breast cancer: overview.

    Science.gov (United States)

    Arteaga, Carlos L

    2013-12-01

    This edition of CCR Focus titled Research in Breast Cancer: Frontiers in Genomics, Biology, and Clinical Investigation reviews six topics that cover areas of translational research of high impact in breast cancer. These topics represent areas of breast cancer research where significant progress has occurred but also where very important challenges remain. The papers in this CCR Focus section are contributed by experts in the respective areas of investigation. Herein, key aspects of these contributions and the research directions they propose are reviewed. ©2013 AACR.

  9. Breast Cancer Chemotherapy and Your Heart

    Science.gov (United States)

    ... of the American Heart Association Cardiology Patient Page Breast Cancer Chemotherapy and Your Heart Christine Unitt , Kamaneh Montazeri , ... Disclosures Footnotes Figures & Tables Info & Metrics eLetters Introduction Breast cancer is the most commonly diagnosed cancer in women. ...

  10. General Information about Male Breast Cancer

    Science.gov (United States)

    ... of the breast are also shown. A family history of breast cancer and other factors can increase ... and organs. This is called metastatic cancer. This animation shows how cancer cells travel from the place ...

  11. Treatment Option Overview (Male Breast Cancer)

    Science.gov (United States)

    ... of the breast are also shown. A family history of breast cancer and other factors can increase ... and organs. This is called metastatic cancer. This animation shows how cancer cells travel from the place ...

  12. Summer Student Breast Cancer Research Training Program

    National Research Council Canada - National Science Library

    Zaloga, Gary P

    2005-01-01

    ... projects addressed the effects of omega-3 lipids upon breast cancer cells. 0mega-3 lipids were found to decrease breast cancer-induced muscle cell proteolysis and to induce apoptosis in cancer cells...

  13. Identification and clinical implications of circulating microRNAs for estrogen receptor-positive breast cancer.

    Science.gov (United States)

    Park, In Hae; Kang, Joo Hyun; Lee, Keun Seok; Nam, Seungyoon; Ro, Jungsil; Kim, Joo-Hang

    2014-12-01

    Cancer-associated microRNAs have been stably detected in blood. The objective of this study was to identify a panel of circulating microRNAs with the potential to serve as biomarkers for estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2 (HER2)- breast cancer. We used microarray-based expression profiling to compare the levels of circulating microRNAs in blood samples from 11 ER+/HER2- advanced breast cancer patients plus 5 age-matched controls. MicroRNA levels were validated by reverse transcription quantitative polymerase chain reaction in 40 control subjects, 187 early breast cancer patients, and 45 metastatic breast cancer patients. Then, we assessed the association between the levels of microRNA and clinical outcomes of ER+/HER2- metastatic breast cancer. Initially, we found that miR-1280, miR-1260, and miR-720 were up-regulated in blood from breast cancer patients (P breast cancer patients and reflected tumor status (controlcancercancer). Among 37 metastatic breast cancer patients, miR-1280 levels significantly decreased after treatment in patients who responded to systemic treatment (P breast cancer patients and may serve as a biomarker for ER-positive breast cancer.

  14. Breast cancer incidence in Mongolia.

    Science.gov (United States)

    Troisi, Rebecca; Altantsetseg, Dalkhjav; Davaasambuu, Ganmaa; Rich-Edwards, Janet; Davaalkham, Dambadarjaa; Tretli, Steinar; Hoover, Robert N; Frazier, A Lindsay

    2012-07-01

    Data on international variation in breast cancer incidence may help to identify additional risk factors. Substantially lower breast cancer rates in Asia than in North America and Western Europe are established, but differences within Asia have been largely ignored despite heterogeneity in lifestyles and environments. Mongolia's breast cancer experience is of interest because of its shared genetics but vastly different diet compared with other parts of Asia. Age-standardized breast cancer incidence and mortality rates obtained from the International Association of Cancer Registries are presented for several Asian countries. Mongolian incidence rates obtained from its cancer registry describe incidence within the country. Breast cancer incidence in Mongolia (age standardized 8.0/100,000) is almost a third of rates in China (21.6/100,000), and over five times that of Japan (42.7/100,000) and Russia (43.2/100,000). Rates within Mongolia appear to have increased slightly over the last decade and are higher in urban than rural areas (annual percentage increase of age-standardized rates from 1998 to 2005 was 3.60 and 2.57 %, respectively). The increase in breast cancer incidence with age plateaus at menopause, as in other Asian populations. Mongolia's low breast cancer incidence is of particular interest because of their unusual diet (primarily red meat and dairy) compared with other Asian countries. More intensive study of potential dietary, reproductive and lifestyle factors in Mongolia with comparison to other Asian populations may provide more clarity in what drives the international breast cancer rate differences.

  15. Obesity Biomarkers, Metabolism and Risk of Cancer: An Epidemiological Perspective.

    Science.gov (United States)

    Nimptsch, Katharina; Pischon, Tobias

    Obesity is associated with metabolic alterations that may pose a biological link between body fatness and risk of cancer. Elucidating the role of obesity-related biomarkers in cancer development is essential for developing targeted strategies aiming at obesity-associated cancer prevention. Molecular epidemiological studies of the past decades have provided evidence that major hormonal pathways linking obesity and cancer risk include the insulin and insulin-like growth factor-1 (IGF-1) axis, sex-steroid hormones, adipokines and chronic low-grade inflammation. These pathways are interrelated with each other, and their importance varies by obesity-related cancer type. The insulin/IGF-1 axis has been implicated to play an important mediating role in the association between obesity and risk of pancreatic, colorectal and prostate cancer. Endogenous sex-steroid hormone concentrations, in particular obesity-associated pre-diagnostic elevations of estrogens and androgens, play an important role in postmenopausal breast cancer and endometrial cancer development. The adipokines adiponectin and leptin and adipocyte-mediated chronic low-grade inflammation represented by the acute-phase C-reactive protein may explain a substantial part of the association between obesity and risk of colorectal cancer. There is less evidence on whether these hormonal pathways play a mediating role in other obesity-associated types of cancer. In this chapter, the molecular epidemiologic evidence from prospective studies relating circulating obesity-related biomarkers to cancer risk is summarized, taking into account available evidence from Mendelian Randomization investigations aiming at improving causal inference.

  16. Miscellaneous syndromes and their management: occult breast cancer, breast cancer in pregnancy, male breast cancer, surgery in stage IV disease.

    Science.gov (United States)

    Colfry, Alfred John

    2013-04-01

    Surgical therapy for occult breast cancer has traditionally centered on mastectomy; however, breast conservation with whole breast radiotherapy followed by axillary lymph node dissection has shown equivalent results. Patients with breast cancer in pregnancy can be safely and effectively treated; given a patient's pregnancy trimester and stage of breast cancer, a clinician must be able to guide therapy accordingly. Male breast cancer risk factors show strong association with BRCA2 mutations, as well as Klinefelter syndrome. Several retrospective trials of surgical therapy in stage IV breast cancer have associated a survival advantage with primary site tumor extirpation. Copyright © 2013 Elsevier Inc. All rights reserved.

  17. Levels of plasma circulating cell free nuclear and mitochondrial DNA as potential biomarkers for breast tumors

    Directory of Open Access Journals (Sweden)

    Diesch Claude

    2009-11-01

    Full Text Available Abstract Background With the aim to simplify cancer management, cancer research lately dedicated itself more and more to discover and develop non-invasive biomarkers. In this connection, circulating cell-free DNA (ccf DNA seems to be a promising candidate. Altered levels of ccf nuclear DNA (nDNA and mitochondrial DNA (mtDNA have been found in several cancer types and might have a diagnostic value. Methods Using multiplex real-time PCR we investigated the levels of ccf nDNA and mtDNA in plasma samples from patients with malignant and benign breast tumors, and from healthy controls. To evaluate the applicability of plasma ccf nDNA and mtDNA as a biomarker for distinguishing between the three study-groups we performed ROC (Receiver Operating Characteristic curve analysis. We also compared the levels of both species in the cancer group with clinicopathological parameters. Results While the levels of ccf nDNA in the cancer group were significantly higher in comparison with the benign tumor group (P P P P = 0.022. The level of ccf nDNA was also associated with tumor-size (2 cmP = 0.034. Using ROC curve analysis, we were able to distinguish between the breast cancer cases and the healthy controls using ccf nDNA as marker (cut-off: 1866 GE/ml; sensitivity: 81%; specificity: 69%; P P Conclusion Our data suggests that nuclear and mitochondrial ccf DNA have potential as biomarkers in breast tumor management. However, ccf nDNA shows greater promise regarding sensitivity and specificity.

  18. Doxorubicin Hydrochloride, Cyclophosphamide, and Filgrastim Followed By Paclitaxel Albumin-Stabilized Nanoparticle Formulation With or Without Trastuzumab in Treating Patients With Breast Cancer Previously Treated With Surgery

    Science.gov (United States)

    2017-08-30

    Estrogen Receptor-positive Breast Cancer; HER2-positive Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer

  19. Basal {sup 18}F-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography as a prognostic biomarker in patients with locally advanced breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Garcia Vicente, Ana Maria; Soriano Castrejon, Angel [University General Hospital, Nuclear Medicine Department, Ciudad Real (Spain); Lopez-Fidalgo, Jesus Fernando; Amo-Salas, Mariano [University of Castilla-La Mancha, Department of Mathematics, Ciudad Real (Spain); Mar Munoz Sanchez, Maria del [Virgen de la Luz Hospital, Oncology Department, Cuenca (Spain); Alvarez Cabellos, Ruth [Virgen de la Salud Hospital, Oncology Department, Toledo (Spain); Espinosa Aunion, Ruth [La Mancha Centro Hospital, Oncology Department, Ciudad Real (Spain)

    2015-11-15

    To explore the relationship between basal {sup 18}F-FDG PET/CT information in breast tumours and survival in locally advanced breast cancer (LABC). This prospective, multicentre study included 198 women diagnosed with LABC. All patients underwent {sup 18}F-FDG PET/CT prior to treatment. The maximum standardized uptake value (SUVmax) in tumor (T), lymph nodes (N) and the N/T ratio was obtained in all cases. Stage according to PET/CT imaging (metabolic stage) and conventional imaging techniques (clinical stage) was established. During follow-up, patient status was established (disease free status or not). The relationship between all the variables and overall survival (OS) and disease-free survival (DFS) was analysed using the Kaplan-Meier and Cox regression methods. A ROC analysis was performed to obtain a cut-off value of SUVmax that was useful in the prediction of outcome. The mean SUVmax ± SD values in the primary tumour, lymph nodes and the SUVmax N/T index were 7.40 ± 5.57, 4.17 ± 4.74 and 0.73 ± 1.20, respectively. Higher semiquantitative metabolic values were found in more advanced metabolic and clinical stages. During follow-up, 78.4 % of patients were free of disease. Significant relationships were observed between SUVT and SUVN and patient status. With respect to OS and DFS, significant differences were detected for the metabolic stage. Kaplan-Meier analysis revealed that using the cut-off values, a primary-tumour SUVmax ≥ 6.05 or a nodal SUVmax ≥2.25 were significantly correlated with DFS and OS. PET imaging with {sup 18}F-FDG offers prognostic information for LABC that can be obtained preoperatively and noninvasively. (orig.)

  20. Protocol for Biomarker Ratio Imaging Microscopy with Specific Application to Ductal Carcinoma in Situ of the Breast

    Directory of Open Access Journals (Sweden)

    Howard Raymond Petty

    2016-11-01

    Full Text Available This protocol describes the methods and steps involved in performing biomarker ratio imaging microscopy (BRIM using formalin fixed paraffin-embedded (FFPE samples of human breast tissue. The technique is based on the acquisition of two fluorescence images of the same microscopic field using two biomarkers and immunochemical tools. The biomarkers are selected such that one biomarker correlates with breast cancer aggressiveness while the second biomarker anti-correlates with aggressiveness. When the former image is divided by the latter image, a computed ratio image is formed that reflects the aggressiveness of tumor cells while increasing contrast and eliminating path-length and other artifacts from the image. For example, the aggressiveness of epithelial cells may be assessed by computing ratio images from N-cadherin and E-cadherin images or CD44 and CD24 images. These ratio micrographs reveal the mesenchymal or stem cell nature of the constituent cells, respectively. This methodology is illustrated for tissue samples of ductal carcinoma in situ (DCIS and invasive breast cancer. This tool should be useful in tissue studies of experimental cancer as well as the management of cancer patients.

  1. Breast Cancer by the Numbers

    OpenAIRE

    2014-01-01

    The American Cancer Society estimates that 40,000 women will die from breast cancer this year. But thanks to steady progress in the war on cancer, millions of U.S. women with a history of the disease are alive today. Key statistics on survival rates, therapies in use, and treatment costs are provided.

  2. Metastatic breast cancer: The Odyssey of personalization.

    Science.gov (United States)

    Sonnenblick, A; Pondé, N; Piccart, M

    2016-10-01

    Metastatic breast cancer is the most frequent cause of cancer death for women worldwide. In the last 15 years, a large number of new agents have entered clinical use, a result of the dramatic increase in our understanding of the molecular underpinnings of metastatic breast cancer. However, while these agents have led to better outcomes, they are also at the root cause of increasing financial pressure on healthcare systems. Moreover, decision making in an era where every year new agents are added to the therapeutic armamentarium has also become a significant challenge for medical oncologists. In the present article, we will provide an ample review on the most recent developments in the field of treatment of the different subtypes of metastatic breast cancer with a critical discussion on the slow progress made in identifying response biomarkers. New hopes in the form of ctDNA monitoring and functional imaging will be presented. Copyright © 2016 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  3. Awareness of Breast Cancer and Practice of Breast Self ...

    African Journals Online (AJOL)

    Background and Objective: Breast cancer is the commonest cancer among women in globally and in Nigeria. In Nigeria, cases of breast cancer cases have been prevalent for three decades and more than 90% of cases can be detected by women themselves through breast self – examination. The objective of this study ...

  4. Altered expression of insulin receptor isoforms in breast cancer.

    Directory of Open Access Journals (Sweden)

    Jiaqi Huang

    Full Text Available PURPOSE: Insulin-like growth factor (IGF signaling through human insulin receptor isoform A (IR-A contributes to tumorigenesis and intrinsic resistance to anti-IGF1R therapy. In the present study, we (a developed quantitative TaqMan real time-PCR-based assays (qRT-PCR to measure human insulin receptor isoforms with high specificity, (b evaluated isoform expression levels in molecularly-defined breast cancer subtypes, and (c identified the IR-A:IR-B mRNA ratio as a potential biomarker guiding patient stratification for anti-IGF therapies. EXPERIMENTAL DESIGN: mRNA expression levels of IR-A and IR-B were measured in 42 primary breast cancers and 19 matched adjacent normal tissues with TaqMan qRT-PCR assays. The results were further confirmed in 165 breast cancers. The tumor samples were profiled using whole genome microarrays and subsequently subtyped using the PAM50 breast cancer gene signature. The relationship between the IR-A:IR-B ratio and cancer subtype, as well as markers of proliferation were characterized. RESULTS: The mRNA expression levels of IR-A in the breast tumors were similar to those observed in the adjacent normal tissues, while the mRNA levels of IR-B were significantly decreased in tumors. The IR-A:IR-B ratio was significantly higher in luminal B breast cancer than in luminal A. Strong concordance between the IR-A:IR-B ratio and the composite Oncotype DX proliferation score was observed for stratifying the latter two breast cancer subtypes. CONCLUSIONS: The reduction in IR-B expression is the key to the altered IR-A:IR-B ratio observed in breast cancer. The IR-A:IR-B ratio may have biomarker utility in guiding a patient stratification strategy for an anti-IGF therapeutic.

  5. Hormones, Women and Breast Cancer

    Science.gov (United States)

    ... women who • Are older • Have no children • Delayed pregnancy until after age 30 • Have used combination hormone therapy (estrogen plus progestin) for more than five years • Have a mother, sister, or daughter who has had breast cancer Did you know? Breast pain alone is not ...

  6. Mps1/TTK: a novel target and biomarker for cancer.

    Science.gov (United States)

    Xie, Yuan; Wang, Anqiang; Lin, Jianzhen; Wu, Liangcai; Zhang, Haohai; Yang, Xiaobo; Wan, Xueshuai; Miao, Ruoyu; Sang, Xinting; Zhao, Haitao

    2017-02-01

    Monopolar spindle1 (Mps1, also known as TTK) is the core component of the spindle assembly checkpoint, which functions to ensure proper distribution of chromosomes to daughter cells. Mps1 is hardly detectable in normal organs except the testis and placenta. However, high levels of Mps1 are found in many types of human malignancies, including glioblastoma, thyroid carcinoma, breast cancer, and other cancers. Several Mps1 inhibitors can inhibit the proliferation of cancer cells and exhibit demonstrable survival benefits. Mps1 can be utilized as a new immunogenic epitope, which is able to induce potent cytotoxic T lymphocyte activity against cancer cells while sparing normal cells. Some clinical trials have validated its safety, immunogenicity and clinical response. Thus, Mps1 may be a novel target for cancer therapy. Mps1 is differentially expressed between normal and malignant tissues, indicating its potential as a molecular biomarker for diagnosis. Meanwhile, the discovery that it clearly correlates with recurrence and survival time suggests it may serve as an independent prognostic biomarker as well.

  7. Current early diagnostic biomarkers of prostate cancer

    Directory of Open Access Journals (Sweden)

    Min Qu

    2014-08-01

    Full Text Available Prostate cancer (PCa has become to have the highest incidence and the second mortality rate in western countries, affecting men's health to a large extent. Although prostate-specific antigen (PSA was discovered to help diagnose the cancer in an early stage for decades, its specificity is relative low, resulting in unnecessary biopsy for healthy people and over-treatment for patients. Thus, it is imperative to identify more and more effective biomarkers for early diagnosis of PCa in order to distinguish patients from healthy populations, which helps guide an early treatment to lower disease-related mortality by noninvasive or minimal invasive approaches. This review generally describes the current early diagnostic biomarkers of PCa in addition to PSA and summarizes the advantages and disadvantages of these biomarkers.

  8. Using Aptamers for Cancer Biomarker Discovery

    Directory of Open Access Journals (Sweden)

    Yun Min Chang

    2013-01-01

    Full Text Available Aptamers are single-stranded synthetic DNA- or RNA-based oligonucleotides that fold into various shapes to bind to a specific target, which includes proteins, metals, and molecules. Aptamers have high affinity and high specificity that are comparable to that of antibodies. They are obtained using iterative method, called (Systematic Evolution of Ligands by Exponential Enrichment SELEX and cell-based SELEX (cell-SELEX. Aptamers can be paired with recent advances in nanotechnology, microarray, microfluidics, and other technologies for applications in clinical medicine. One particular area that aptamers can shed a light on is biomarker discovery. Biomarkers are important in diagnosis and treatment of cancer. In this paper, we will describe ways in which aptamers can be used to discover biomarkers for cancer diagnosis and therapeutics.

  9. Association of breast cancer risk loci with breast cancer survival.

    Science.gov (United States)

    Barrdahl, Myrto; Canzian, Federico; Lindström, Sara; Shui, Irene; Black, Amanda; Hoover, Robert N; Ziegler, Regina G; Buring, Julie E; Chanock, Stephen J; Diver, W Ryan; Gapstur, Susan M; Gaudet, Mia M; Giles, Graham G; Haiman, Christopher; Henderson, Brian E; Hankinson, Susan; Hunter, David J; Joshi, Amit D; Kraft, Peter; Lee, I-Min; Le Marchand, Loic; Milne, Roger L; Southey, Melissa C; Willett, Walter; Gunter, Marc; Panico, Salvatore; Sund, Malin; Weiderpass, Elisabete; Sánchez, María-José; Overvad, Kim; Dossus, Laure; Peeters, Petra H; Khaw, Kay-Tee; Trichopoulos, Dimitrios; Kaaks, Rudolf; Campa, Daniele

    2015-12-15

    The survival of breast cancer patients is largely influenced by tumor characteristics, such as TNM stage, tumor grade and hormone receptor status. However, there is growing evidence that inherited genetic variation might affect the disease prognosis and response to treatment. Several lines of evidence suggest that alleles influencing breast cancer risk might also be associated with breast cancer survival. We examined the associations between 35 breast cancer susceptibility loci and the disease over-all survival (OS) in 10,255 breast cancer patients from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3) of which 1,379 died, including 754 of breast cancer. We also conducted a meta-analysis of almost 35,000 patients and 5,000 deaths, combining results from BPC3 and the Breast Cancer Association Consortium (BCAC) and performed in silico analyses of SNPs with significant associations. In BPC3, the C allele of LSP1-rs3817198 was significantly associated with improved OS (HRper-allele =0.70; 95% CI: 0.58-0.85; ptrend  = 2.84 × 10(-4) ; HRheterozygotes  = 0.71; 95% CI: 0.55-0.92; HRhomozygotes  = 0.48; 95% CI: 0.31-0.76; p2DF  = 1.45 × 10(-3) ). In silico, the C allele of LSP1-rs3817198 was predicted to increase expression of the tumor suppressor cyclin-dependent kinase inhibitor 1C (CDKN1C). In the meta-analysis, TNRC9-rs3803662 was significantly associated with increased death hazard (HRMETA =1.09; 95% CI: 1.04-1.15; ptrend  = 6.6 × 10(-4) ; HRheterozygotes  = 0.96 95% CI: 0.90-1.03; HRhomozygotes  = 1.21; 95% CI: 1.09-1.35; p2DF =1.25 × 10(-4) ). In conclusion, we show that there is little overlap between the breast cancer risk single nucleotide polymorphisms (SNPs) identified so far and the SNPs associated with breast cancer prognosis, with the possible exceptions of LSP1-rs3817198 and TNRC9-rs3803662. © 2015 UICC.

  10. Chemical Biomarkers of Human Breast Milk Pollution

    Directory of Open Access Journals (Sweden)

    Benedetta Marchi

    2008-01-01

    Full Text Available Human milk is, without question, the best source of nutrition for infants containing the optimal balance of fats, carbohydrates and proteins for developing babies. Breastfeeding provides a range of benefits for growth, immunity and development building a powerful bond between mother and her child. Recognition of the manifold benefits of breast milk has led to the adoption of breast-feeding policies by numerous health and professional organizations such as the World Health Organization and American Academy of Pediatrics.In industrially developed as well as in developing nations, human milk contamination by toxic chemicals such as heavy metals, dioxins and organohalogen compounds, however, is widespread and is the consequence of decades of inadequately controlled pollution. Through breastfeeding, the mother may transfer to the suckling infant potentially toxic chemicals to which the mother has previously been exposed.In the present review, environmental exposure, acquisition and current levels of old and emerging classes of breast milk pollutants are systematically presented. Although scientific evidences indicated that the advantages of breast-feeding outweigh any risks from contaminants, it is important to identify contaminant trends, to locate disproportionately exposed populations, and to take public health measures to improve chemical BM pollution as possible.

  11. Understanding your breast cancer risk

    Science.gov (United States)

    ... BRCA2, and others increase your risk. Gene mutations account for about 10% of all breast cancer cases. ... urac.org). URAC's accreditation program is an independent audit to verify that A.D.A.M. follows ...

  12. Height and Breast Cancer Risk

    DEFF Research Database (Denmark)

    Zhang, Ben; Shu, Xiao-Ou; Delahanty, Ryan J

    2015-01-01

    BACKGROUND: Epidemiological studies have linked adult height with breast cancer risk in women. However, the magnitude of the association, particularly by subtypes of breast cancer, has not been established. Furthermore, the mechanisms of the association remain unclear. METHODS: We performed a meta......-analysis to investigate associations between height and breast cancer risk using data from 159 prospective cohorts totaling 5216302 women, including 113178 events. In a consortium with individual-level data from 46325 case patients and 42482 control patients, we conducted a Mendelian randomization analysis using...... a genetic score that comprised 168 height-associated variants as an instrument. This association was further evaluated in a second consortium using summary statistics data from 16003 case patients and 41335 control patients. RESULTS: The pooled relative risk of breast cancer was 1.17 (95% confidence...

  13. Danish Breast Cancer Cooperative Group

    DEFF Research Database (Denmark)

    Christiansen, Peer; Ejlertsen, Bent; Jensen, Maj-Britt

    2016-01-01

    AIM OF DATABASE: Danish Breast Cancer Cooperative Group (DBCG), with an associated database, was introduced as a nationwide multidisciplinary group in 1977 with the ultimate aim to improve the prognosis in breast cancer. Since then, the database has registered women diagnosed with primary invasive...... nonmetastatic breast cancer. The data reported from the departments to the database included details of the characteristics of the primary tumor, of surgery, radiotherapy, and systemic therapies, and of follow-up reported on specific forms from the departments in question. DESCRIPTIVE DATA: From 1977 through...... 2014, ~110,000 patients are registered in the nationwide, clinical database. The completeness has gradually improved to more than 95%. DBCG has continuously prepared evidence-based guidelines on diagnosis and treatment of breast cancer and conducted quality control studies to ascertain the degree...

  14. Palbociclib for Advanced Breast Cancer

    Science.gov (United States)

    An interim analysis of the PALOMA3 trial shows that women with hormone receptor-positive metastatic breast cancer who received palbociclib plus fulvestrant had longer progression-free survival rates than women who received a placebo plus fulvestrant.

  15. Does Aluminium Trigger Breast Cancer?

    Directory of Open Access Journals (Sweden)

    Peter Jennrich

    2016-08-01

    Full Text Available Summary. Breast cancer is by far the most common cancer in women in the western world. In 90% of breast cancers, environmental factors are among the causes. The frequency with which the tumour occurs in the outer upper part of the breast has risen with above average rates in recent decades. Aluminium salts as ingredients in deodorants and antiperspirants are being absorbed by the body to a greater extent than hitherto assumed. Their toxicity for healthy and diseased breast tissue cells includes various well-documented pathomechanisms. In the sense of primary and secondary prevention, the cancer-triggering potential of aluminium and its use in anti-perspirant deodorants must be re-evaluated. For the same reason the access to a targeted diagnosis and treatment of aluminium loading must be facilitated.

  16. Melatonin, Aging and Breast Cancer

    National Research Council Canada - National Science Library

    Hill, Steven

    2001-01-01

    ... conditions for tumor induction, promotion and progression. The pineal gland, via its hormone melatonin, has been shown by numerous laboratories to inhibit the proliferation of both human and animal models of breast cancer...

  17. Validation of Biomarkers for Prostate Cancer Prognosis

    Science.gov (United States)

    2016-11-01

    prostate cancer is the development of biomarkers that predict occult or incipient aggressive disease in the low-risk population. To address this...8-10 vs. <=6 5.13 1.92 13.75 0.001 6. P27 is not significantly associated with RFS after adjusting for clinical predictors (Manuscript in

  18. BREAST CANCER, DERMATOFIBROMAS AND ARSENIC

    OpenAIRE

    Dantzig Paul

    2009-01-01

    Background: Dermatofibromas are common benign tumors in women, and breast cancer is the most common malignancy in women. The aim of this study is to determine if there is any relationship between the two conditions. Materials and Methods: Five patients with dermatofibromas and 10 control patients (two groups) had their skin biopsies measured for arsenic by inductively coupled mass spectrometry. Fifty randomly selected patients with breast cancer and 50 control patients were examined for...

  19. Role of MicroRNA Regulation in Obesity-Associated Breast Cancer: Nutritional Perspectives.

    Science.gov (United States)

    Kasiappan, Ravi; Rajarajan, Dheeran

    2017-11-01

    Breast cancer is the most common malignancy diagnosed in women, and the incidence of breast cancer is increasing every year. Obesity has been identified as one of the major risk factors for breast cancer progression. The mechanisms by which obesity contributes to breast cancer development is not yet understood; however, there are a few mechanisms counted as potential producers of breast cancer in obesity, including insulin resistance, chronic inflammation and inflammatory cytokines, adipokines, and sex hormones. Recent emerging evidence suggests that alterations in microRNA (miRNA) expressions are found in several diseases, including breast cancer and obesity; however, miRNA roles in obesity-linked breast cancer are beginning to unravel. miRNAs are thought to be potential noninvasive biomarkers for diagnosis and prognosis of cancer patients with comorbid conditions of obesity as well as therapeutic targets. Recent studies have evidenced that nutrients and other dietary factors protect against cancer and obesity through modulation of miRNA expressions. Herein, we summarize a comprehensive overview of up-to-date information related to miRNAs and their molecular targets involved in obesity-associated breast cancer. We also address the mechanisms by which dietary factors modulate miRNA expression and its protective roles in obesity-associated breast cancer. It is hoped that this review would provide new therapeutic strategies for the treatment of obesity-associated breast cancer to reduce the burden of breast cancer. © 2017 American Society for Nutrition.

  20. Breast cancer epigenetics: review article

    Directory of Open Access Journals (Sweden)

    Bahareh Abbasi

    2016-11-01

    Full Text Available Stable molecular changes during cell division without any change in the sequence of DNA molecules is known as epigenetic. Molecular mechanisms involved in this process, including histone modifications, methylation of DNA, protein complex and RNA antisense. Cancer genome changes happen through a combination of DNA hypermethylation, long-term epigenetic silencing with heterozygosis loss and genomic regions loss. Different combinations of N-terminal’s changes cooperate with histone variants with a specific role in gene regulation. It have led to load a setting histone that determine transcription potential of a particular gene or genomic regions. DNA methylation analysis in genome region using methylation-specific digital karyotyping of normal breast tissue detect gene expression patterns and DNA specific methylation can be found in breast carcinoma too more than 100 genes in breast tumors or cell lines of breast cancer are reported hypermethylated. Important of DNA methylation on cancer has been concentrated CpG islands hypermethylation. Most of the techniques are able to identify hypermethylated areas. Often, methylated genes play important role in cell cycle regulation, apoptosis, metastasis and tissue invasion, angiogenesis and hormonal signaling. Cyclin D2 (CCND2 gene is an important regulator of cell cycle and increased of expression inhibits the transition from G1 to S cell cycle. This gene is frequently methylated in breast cancer and has been proposed as the first event. Other cell cycle regulator is p16ink4A / CDKN2A that methylated in a large number of human cancers, including breast cancer. Another regulator of the proliferation of breast cancer that methylated is tumor suppressor RAR-β cancer that has been found in lobular and ductal carcinoma. Recent studies have showed the role of epigenetic silencing in the pathogenesis of breast cancer in which tumor suppressor genes have been changed by acetylation and DNA deacetylation

  1. Murine model of hepatic breast cancer.

    Science.gov (United States)

    Rikhi, Rishi; Wilson, Elizabeth M; Deas, Olivier; Svalina, Matthew N; Bial, John; Mansoor, Atiya; Cairo, Stefano; Keller, Charles

    2016-12-01

    Breast cancer is the most common cancer in women and the second leading cause of cancer-related deaths in this population. Breast cancer related deaths have declined due to screening and adjuvant therapies, yet a driving clinical need exists to better understand the cause of the deadliest aspect of breast cancer, metastatic disease. Breast cancer metastasizes to several distant organs, the liver being the third most common site. To date, very few murine models of hepatic breast cancer exist. In this study, a novel murine model of liver breast cancer using the MDA-MB-231 cell line is introduced as an experimental (preclinical) model. Histological typing revealed consistent hepatic breast cancer tumor foci. Common features of the murine model were vascular invasion, lung metastasis and peritoneal seeding. The novel murine model of hepatic breast cancer established in this study provides a tool to be used to investigate mechanisms of hepatic metastasis and to test potential therapeutic interventions.

  2. Basal (18)F-FDG PET/CT as a predictive biomarker of tumor response for neoadjuvant therapy in breast cancer.

    Science.gov (United States)

    García Vicente, A M; Soriano Castrejón, A; Pruneda-González, R E; Fernández Calvo, G; Muñoz Sánchez, M M; Álvarez Cabellos, R; Espinosa Aunión, R; Relea Calatayud, F

    2016-01-01

    To explore the relation between tumor kinetic assessed by (18)F-FDG PET and final neoadjuvant chemotherapy (NC) response within a molecular phenotype perspective. Prospective study included 144 women with breast cancer. All patients underwent a dual-time point (18)F-FDG PET/CT previous to NC. The retention index (RI), between SUV-1 and SUV-2 was calculated. Molecular subtypes were re-grouped in low, intermediate and high-risk biological phenotypes. After NC, all residual primary tumor specimens were histopathologically classified in tumor regression grades (TRG) and response groups. The relation between SUV-1, SUV-2 and RI with the TRG and response groups was evaluated in all molecular subtypes and in accordance with the risk categories. Responder's lesions showed significant greater SUVmax compared to non-responders. The RI value did not show any significant relation with response. Attending to molecular phenotypes, statistical differences were observed with greater SUV for responders having high-risk molecular subtypes. Glycolytic tumor characteristics showed a significant correlation with NC response and dependence of risk phenotype. Copyright © 2015 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

  3. Breast cancer, dermatofibromas and arsenic.

    Science.gov (United States)

    Dantzig, Paul I

    2009-01-01

    Dermatofibromas are common benign tumors in women, and breast cancer is the most common malignancy in women. The aim of this study is to determine if there is any relationship between the two conditions. Five patients with dermatofibromas and 10 control patients (two groups) had their skin biopsies measured for arsenic by inductively coupled mass spectrometry. Fifty randomly selected patients with breast cancer and 50 control patients were examined for the presence of dermatofibromas. The dermatofibromas were found to have an arsenic concentration of 0.171 micrograms/gram, compared with 0.06 and 0.07 micrograms/gram of the two control groups. Forty-three out of 50 patients with breast cancer had dermatofibromas and 32/50 patients with breast cancer had multiple dermatofibromas, compared to 10/50 control patients with dermatofibromas and only 1/50 with multiple dermatofibromas. Arsenic is important in the development of dermatofibromas and dermatofibromas represent a reservoir and important sign of chronic arsenic exposure. Dermatofibromas represent an important sign for women at risk for breast cancer, and arsenic may represent the cause of the majority of cases of breast cancer.

  4. Breast cancer, dermatofibromas and arsenic

    Directory of Open Access Journals (Sweden)

    Dantzig Paul

    2009-01-01

    Full Text Available Background: Dermatofibromas are common benign tumors in women, and breast cancer is the most common malignancy in women. The aim of this study is to determine if there is any relationship between the two conditions. Materials and Methods: Five patients with dermatofibromas and 10 control patients (two groups had their skin biopsies measured for arsenic by inductively coupled mass spectrometry. Fifty randomly selected patients with breast cancer and 50 control patients were examined for the presence of dermatofibromas. Results: The dermatofibromas were found to have an arsenic concentration of 0.171 micrograms/gram, compared with 0.06 and 0.07 micrograms/gram of the two control groups. Forty-three out of 50 patients with breast cancer had dermatofibromas and 32/50 patients with breast cancer had multiple dermatofibromas, compared to 10/50 control patients with dermatofibromas and only 1/50 with multiple dermatofibromas. Conclusions: Arsenic is important in the development of dermatofibromas and dermatofibromas represent a reservoir and important sign of chronic arsenic exposure. Dermatofibromas represent an important sign for women at risk for breast cancer, and arsenic may represent the cause of the majority of cases of breast cancer.

  5. Epigenetic mechanisms of breast cancer: an update of the current knowledge.

    Science.gov (United States)

    Karsli-Ceppioglu, Seher; Dagdemir, Aslihan; Judes, Gaëlle; Ngollo, Marjolaine; Penault-Llorca, Frédérique; Pajon, Amaury; Bignon, Yves-Jean; Bernard-Gallon, Dominique

    2014-01-01

    Epigenetic alterations are heritable changes in gene expression that occur without causing any change in DNA sequence. They are important key factors for cancer development and prognosis. Breast cancer is induced by the accumulation of altered gene regulation. Besides genetic mutations, epigenetics mechanisms have an important role in breast cancer tumorigenesis. Investigations related with aberrant epigenetic regulations in breast cancer focus on initiating molecular mechanisms in cancer development, identification of new biomarkers to predict breast cancer aggressiveness and the potential of epigenetic therapy. In this review, we will summarize the recent knowledge about the role of epigenetic alterations related with DNA methylation and histone modification in breast cancer. In addition, altered regulation of breast cancer specific genes and the potential of epigenetic therapy will be discussed according to epigenetic mechanisms.

  6. Prognosis of pregnancy-associated breast cancer.

    Science.gov (United States)

    Lee, Guek Eng; Mayer, Erica L; Partridge, Ann

    2017-06-01

    Conventionally, breast cancer diagnosed during pregnancy and within the years following have been referred to collectively as pregnancy-associated breast cancer. However, increasing evidence suggests that breast cancer diagnosed during pregnancy is a different entity from that diagnosed postpartum, both in terms of prognosis and biology. Given the increasing number of women who find themselves diagnosed with breast cancer during or following a pregnancy, future research and discussion should separate these two into distinct groups: breast cancer diagnosed during pregnancy and breast cancer diagnosed postpartum in an effort to enhance our understanding to inform and improve clinical management and counseling.

  7. Occupational exposure and risk of breast cancer

    OpenAIRE

    Fenga, Concettina

    2016-01-01

    Breast cancer is a multifactorial disease and the most commonly diagnosed cancer in women. Traditional risk factors for breast cancer include reproductive status, genetic mutations, family history and lifestyle. However, increasing evidence has identified an association between breast cancer and occupational factors, including environmental stimuli. Epidemiological and experimental studies demonstrated that ionizing and non-ionizing radiation exposure, night-shift work, pesticides, polycyclic...

  8. Proteomic biomarkers in lung cancer.

    Science.gov (United States)

    Pastor, M D; Nogal, A; Molina-Pinelo, S; Carnero, A; Paz-Ares, L

    2013-09-01

    The correct understanding of tumour development relies on the comprehensive study of proteins. They are the main orchestrators of vital processes, such as signalling pathways, which drive the carcinogenic process. Proteomic technologies can be applied to cancer research to detect differential protein expression and to assess different responses to treatment. Lung cancer is the number one cause of cancer-related death in the world. Mostly diagnosed at late stages of the disease, lung cancer has one of the lowest 5-year survival rates at 15 %. The use of different proteomic techniques such as two-dimensional gel electrophoresis (2D-PAGE), isotope labelling (ICAT, SILAC, iTRAQ) and mass spectrometry may yield new knowledge on the underlying biology of lung cancer and also allow the development of new early detection tests and the identification of changes in the cancer protein network that are associated with prognosis and drug resistance.

  9. Advocacy groups for breast cancer patients.

    OpenAIRE

    Waller, M.; Batt, S

    1995-01-01

    Breast cancer patient advocacy groups emerged in the 1990s to support and empower women with breast cancer. Women with cancer and oncologists tend to have divergent perspectives on how breast cancer prevention should be defined and what the priorities for research should be. As their American counterparts have done, breast cancer patient advocates in Canada are seeking greater participation in decision making with respect to research. To date they have had more input into research policy deci...

  10. Danish Breast Cancer Cooperative Group

    Directory of Open Access Journals (Sweden)

    Christiansen P

    2016-10-01

    Full Text Available Peer Christiansen,1 Bent Ejlertsen,2,3 Maj-Britt Jensen,3 Henning Mouridsen3 1Department of Surgery P, Breast Surgery Unit, Aarhus University Hospital/Randers Regional Hospital, Aarhus C, 2Department of Oncology, Rigshospitalet, Copenhagen University Hospital, 3DBCG-secretariat, Department 2501, Rigshospitalet, Copenhagen Ø, Denmark Aim of database: Danish Breast Cancer Cooperative Group (DBCG, with an associated database, was introduced as a nationwide multidisciplinary group in 1977 with the ultimate aim to improve the prognosis in breast cancer. Since then, the database has registered women diagnosed with primary invasive nonmetastatic breast cancer. The data reported from the departments to the database included details of the characteristics of the primary tumor, of surgery, radiotherapy, and systemic therapies, and of follow-up reported on specific forms from the departments in question. Descriptive data: From 1977 through 2014, ~110,000 patients are registered in the nationwide, clinical database. The completeness has gradually improved to more than 95%. DBCG has continuously prepared evidence-based guidelines on diagnosis and treatment of breast cancer and conducted quality control studies to ascertain the degree of adherence to the guidelines in the different departments. Conclusion: Utilizing data from the DBCG database, a long array of high-quality DBCG studies of various designs and scope, nationwide or in international collaboration, have contributed to the current updating of the guidelines, and have been an instrumental resource in the improvement of management and prognosis of breast cancer in Denmark. Thus, since the establishment of DBCG, the prognosis in breast cancer has continuously improved with a decrease in 5-year mortality from ~37% to 15%. Keywords: breast cancer, database, guidelines, quality control, research

  11. [Hereditary breast and ovarian cancer].

    Science.gov (United States)

    Lax, S F

    2017-05-01

    Hereditary breast and ovarian carcinomas are frequently caused by germline mutations of the BRCA1 and BRCA2 genes (BRCA1/2 syndromes) and are often less associated with other hereditary syndromes such as Li-Fraumeni and Peutz-Jeghers. The BRCA1/2 proteins have a special role in DNA repair. Therefore, loss of function due to mutation causes an accumulation of mutations in other genes and subsequent tumorigenesis at an early age. BRCA1/2 mutations are irregularly distributed over the length of the genes without hot spots, although special mutations are known. Breast and ovarian cancer occur far more frequently in women with BRCA1/2 germline mutations compared with the general population. Breast cancer occurs increasingly from the age of 30, ovarian cancer in BRCA1 syndrome from the age of 40 and BRCA2 from the age of 50. Suspicion of a BRCA syndrome should be prompted in the case of clustering of breast cancer in 1st degree relatives, in particular at a young age, if breast and ovarian cancer have occurred, and if cases of male breast cancer are known. Breast carcinomas with medullary differentiation seem to predominate in BRCA syndromes, but other carcinoma types may also occur. BRCA germline mutations seem to occur frequently in triple-negative breast carcinomas, whereas an association with ductal carcinoma in situ (DCIS) is rare. Ovarian carcinomas in BRCA syndromes are usually high-grade serous, mucinous carcinomas and borderline tumors are unusual. Pathology plays a special role within the multidisciplinary team in the recognition of patients with hereditary cancer syndromes.

  12. Dutch digital breast cancer screening: implications for breast cancer care.

    Science.gov (United States)

    Timmers, Johanna M; den Heeten, Gerard J; Adang, Eddy M; Otten, Johannes D; Verbeek, André L; Broeders, Mireille J

    2012-12-01

    In comparison to other European population-based breast cancer screening programmes, the Dutch programme has a low referral rate, similar breast cancer detection and a high breast cancer mortality reduction. The referral rate in the Netherlands has increased over time and is expected to rise further, mainly following nationwide introduction of digital mammography, completed in 2010. This study explores the consequences of the introduction of digital mammography on the balance between referral rate, detection of breast cancer, diagnostic work-up and associated costs. Detailed information on diagnostic work-up (chart review) was obtained from referred women (n = 988) in 2000-06 (100% analogue mammography) and 2007 (75% digital mammography) in Nijmegen, the Netherlands. The average referral rate increased from 15 (2000-06) to 34 (2007) per 1000 women screened. The number of breast cancers detected increased from 5.5 to 7.8 per 1000 screens, whereas the positive predictive value fell from 37% to 23%. A sharp rise in diagnostic work-up procedures and total diagnostic costs was seen. On the other hand, costs of a single work-up slightly decreased, as less surgical biopsies were performed. Our study shows that a low referral rate in combination with the introduction of digital mammography affects the balance between referral rate and detection rate and can substantially influence breast cancer care and associated costs. Referral rates in the Netherlands are now more comparable to other countries. This effect is therefore of value in countries where implementation of digital breast cancer screening has just started or is still under discussion.

  13. Awareness and current knowledge of breast cancer.

    Science.gov (United States)

    Akram, Muhammad; Iqbal, Mehwish; Daniyal, Muhammad; Khan, Asmat Ullah

    2017-10-02

    Breast cancer remains a worldwide public health dilemma and is currently the most common tumour in the globe. Awareness of breast cancer, public attentiveness, and advancement in breast imaging has made a positive impact on recognition and screening of breast cancer. Breast cancer is life-threatening disease in females and the leading cause of mortality among women population. For the previous two decades, studies related to the breast cancer has guided to astonishing advancement in our understanding of the breast cancer, resulting in further proficient treatments. Amongst all the malignant diseases, breast cancer is considered as one of the leading cause of death in post menopausal women accounting for 23% of all cancer deaths. It is a global issue now, but still it is diagnosed in their advanced stages due to the negligence of women regarding the self inspection and clinical examination of the breast. This review addresses anatomy of the breast, risk factors, epidemiology of breast cancer, pathogenesis of breast cancer, stages of breast cancer, diagnostic investigations and treatment including chemotherapy, surgery, targeted therapies, hormone replacement therapy, radiation therapy, complementary therapies, gene therapy and stem-cell therapy etc for breast cancer.

  14. ODAM Expression Inhibits Human Breast Cancer Tumorigenesis

    Science.gov (United States)

    Kestler, Daniel P.; Foster, James S.; Bruker, Charles T.; Prenshaw, John W.; Kennel, Stephen J.; Wall, Jonathan S.; Weiss, Deborah T.; Solomon, Alan

    2011-01-01

    We have posited that Odontogenic Ameloblast Associated Protein (ODAM) serves as a novel prognostic biomarker in breast cancer and now have investigated its potential role in regulating tumor growth and metastasis. Human breast cancer MDA-MB-231 cells were transfected with a recombinant ODAM plasmid construct (or, as a control, the plasmid vector alone). ODAM expression increased adhesion and apoptosis of the transfected MDA-MB-231 cells and suppressed their growth rate, migratory activity, and capability to invade extracellular matrix-coated membranes. Implantation of such cells into mouse mammary fat pads resulted in significantly smaller tumors than occurred in animals that received control cells; furthermore, ODAM-expressing cells, when injected intravenously into mice, failed to metastasize, whereas the control-transfected counterparts produced extensive lung lesions. Our finding that induction of ODAM expression in human breast cancer cells markedly inhibited their neoplastic properties provides further evidence for the regulatory role of this molecule in tumorigenesis and, consequently, is of potential clinical import. PMID:21603257

  15. Identification of miR-10b, miR-26a, miR-146a and miR-153 as potential triple-negative breast cancer biomarkers.

    Science.gov (United States)

    Fkih M'hamed, Insaf; Privat, Maud; Ponelle, Flora; Penault-Llorca, Frédérique; Kenani, Abderraouf; Bignon, Yves-Jean

    2015-12-01

    Familial triple-negative breast cancers are often linked to mutations in the BRCA1 tumor suppressor gene. In sporadic triple-negative breast cancers BRCA1 is frequently inactivated at the transcriptional level, and it has been reported that this inactivation may be brought about by promoter methylation. More recently, it was found that BRCA1 may also be regulated at the post-transcriptional level by miRNAs. Here, we explored the expression of putative BRCA1-regulating miRNAs in sporadic human triple-negative breast cancer cells. Nine sporadic human breast cancer-derived cell lines and one benign breast epithelium-derived cell line were assessed for their hormone receptor, growth factor receptor and cytokeratin status by immunocytochemistry. The expression of 5 selected miRNAs predicted to target BRCA1 was assessed using qRT-PCR in the 10 cell lines. In addition, expression profiles of 84 known breast cancer-associated miRNAs were established in these 10 cell lines using PCR Array and qRT-PCR, respectively. The putative role of pre-selected candidate miRNAs in breast cancer development was assessed through exogenous expression of these miRNAs and their anti-miRNAs ('antagomirs') in MDA-MB-231 and MCF7 breast cancer-derived cells. Based on our expression profiling results, four candidate miRNAs (miR-10b, miR-26a, miR-146a and miR-153) were selected as being potentially involved in triple-negative breast cancer development. Exogenous expression assays revealed that miR-10b and miR-26a, but not miR-146a, can down-regulate the expression of BRCA1 in both triple-negative MDA-MB-231 and luminal epithelial MCF7 breast cancer-derived cells, whereas miR-153 could down-regulate BRCA1 expression only in MCF7 cells. In silico analysis of The Cancer Genome Atlas (TCGA) data confirmed that miR-146a is significantly higher expressed in triple-negative breast tumors compared to other (non triple-negative) breast tumors. Our work provides evidence for the involvement of specific mi

  16. Molecular alterations and biomarkers in colorectal cancer

    Science.gov (United States)

    Grady, William M.; Pritchard, Colin C.

    2013-01-01

    The promise of precision medicine is now a clinical reality. Advances in our understanding of the molecular genetics of colorectal cancer genetics is leading to the development of a variety of biomarkers that are being used as early detection markers, prognostic markers, and markers for predicting treatment responses. This is no more evident than in the recent advances in testing colorectal cancers for specific molecular alterations in order to guide treatment with the monoclonal antibody therapies cetuximab and panitumumab, which target the epidermal growth factor receptor (EGFR). In this review, we update a prior review published in 2010 and describe our current understanding of the molecular pathogenesis of colorectal cancer and how these alterations relate to emerging biomarkers for early detection and risk stratification (diagnostic markers), prognosis (prognostic markers), and the prediction of treatment responses (predictive markers). PMID:24178577

  17. Epidemiology of breast cancer subtypes in two prospective cohort studies of breast cancer survivors

    National Research Council Canada - National Science Library

    Kwan, Marilyn L; Kushi, Lawrence H; Weltzien, Erin; Maring, Benjamin; Kutner, Susan E; Fulton, Regan S; Lee, Marion M; Ambrosone, Christine B; Caan, Bette J

    2009-01-01

    The aim of this study was to describe breast tumor subtypes by common breast cancer risk factors and to determine correlates of subtypes using baseline data from two pooled prospective breast cancer...

  18. Proteomic analysis of tissue samples in translational breast cancer research

    DEFF Research Database (Denmark)

    Gromov, Pavel; Moreira, José; Gromova, Irina

    2014-01-01

    In the last decade, many proteomic technologies have been applied, with varying success, to the study of tissue samples of breast carcinoma for protein expression profiling in order to discover protein biomarkers/signatures suitable for: characterization and subtyping of tumors; early diagnosis, ...... the translation of basic discoveries into the daily breast cancer clinical practice. In particular, we address major issues in experimental design by reviewing the strengths and weaknesses of current proteomic strategies in the context of the analysis of human breast tissue specimens....

  19. Endocrine determinants of breast density and breast cancer

    NARCIS (Netherlands)

    Verheus, M.

    2007-01-01

    Worldwide, breast cancer is the most common malignancy among females. The total breast area on a mammogram can be dived in a radiologicaly dense area (glandular and stromal tissue) and a non-dense area (mainly fat tissue). Women with a high proportion of dense breast tissue (percent breast density)

  20. Selection of a breast cancer subpopulation-specific antibody using phage display on tissue sections

    DEFF Research Database (Denmark)

    Larsen, Simon Asbjørn; Meldgaard, Theresa; Fridriksdottir, Agla J

    2015-01-01

    on cryostat sections of human breast cancer tissue. This method allows for selection of recombinant antibodies binding to antigens specifically expressed in a small part of the tissue section. In this case, a CD271(+) subpopulation of breast cancer cells was targeted, and these may be potential breast cancer...... it is possible to better target cellular heterogeneity in proteomic studies. The identification of novel biomarkers is relevant for our understanding and intervention in human diseases. The selection of the breast cancer-specific antibody fragment LH 7 may reveal novel subpopulation-specific biomarkers, which......Breast cancer tumors are composed of heterogeneous cell populations. These populations display a high variance in morphology, growth and metastatic propensity. They respond differently to therapeutic interventions, and some may be more prone to cause recurrence. Studying individual subpopulations...

  1. Endocrine Therapy of Breast Cancer

    Science.gov (United States)

    2009-06-01

    Penninger JM, Kroemer G. AIF and cyclophilin A coop- erate in apoptosis-associated chromatinolysis. Oncogene 2004; 23:1514–1521. Cardoso F, Durbecq V, Laes ...effects of estrogen and antie- strogen on in vitro clonogenic growth of human breast cancers in soft agar, J. Natl. Cancer Inst. 82 (1990) 1146–1149

  2. Chemoprevention of breast cancer in the older patient.

    Science.gov (United States)

    Minton, S E

    2000-02-01

    serum lipids and incidence of osteoporotic bone fractures. The development of SERMs results from an understanding of novel mechanisms of ER modulation and allows targeting for favorable effects in specific tissues. The challenge is to develop an ideal SERM that is effective in preventing breast cancer and does not increase the risk of endometrial cancer, while providing beneficial estrogenic effects on serum lipids and bone mineral density changes. Estrogen receptor-mediated intracellular processes are complex. There are at least two different types of estrogen receptors. The alpha receptors predominate in the breast and uterus, and the beta receptors predominate in the bone and blood vessels. Many proteins also interact with these receptors as co-activators or co-repressors. Transcription-activating factors modulate the effects of estrogen on its target genes. Future prevention strategies may use a combined targeted approach to inhibit ER-mediated cancer progression pathways. The retinoids are under investigation in prevention studies for a multitude of cancers, because they have been shown to inhibit cellular proliferation and to induce cellular differentiation. The retinoid 4HPR was selected for use in breast cancer prevention studies because of its low toxicity profile and prevention efficacy in preclinical studies. It is now being used in combination with tamoxifin in a phase II breast cancer prevention trial. Multiple surrogate endpoint biomarkers are being measured before and after treatment, including measurement of serum IGF-I levels. Future directions in breast cancer prevention include the development of more potent hormonal therapies that completely inhibit ER-mediated cancer progression and, ultimately, multitargeted therapies involving agents that work synergistically.

  3. Women with Disabilities and Breast Cancer Screening

    Science.gov (United States)

    ... Reasonable Accommodations (RA) Women with Disabilities and Breast Cancer Screening Language: English (US) Español (Spanish) Recommend on Facebook ... Mammogram During the Past Two Years 1 Breast Cancer Screening Recommendations 2 If you are between the ages ...

  4. Avoiding risk information about breast cancer.

    Science.gov (United States)

    Melnyk, Darya; Shepperd, James A

    2012-10-01

    Learning about personal risk can provide numerous benefits yet people sometimes opt to remain ignorant. Two studies examined the role of perceived control, coping resources, and anticipated regret in women's decision to avoid breast cancer risk information. Women completed a health inventory and then read a brochure about either controllable or uncontrollable predictors of breast cancer, or received no brochure. Participants then received an opportunity to learn their lifetime risk for breast cancer based on their inventory responses. Reading about controllable predictors of breast cancer reduced avoidance of risk information compared with reading about uncontrollable predictors or receiving no information. In addition, fewer coping resources, anticipated greater regret over seeking breast cancer risk information, and less regret over avoiding breast cancer risk information predicted information avoidance. Reading about controllable predictors of breast cancer reduces avoidance of breast cancer risk information.

  5. Breast Cancer and Estrogen-Alone Update

    Science.gov (United States)

    ... Current Issue Past Issues Research News From NIH Breast Cancer and Estrogen-Alone Update Past Issues / Summer 2006 ... hormone therapy does not increase the risk of breast cancer in postmenopausal women, according to an updated analysis ...

  6. Breast Cancer and the Environment Research Program

    Science.gov (United States)

    The Breast Cancer and the Environment Research Program supports a multidisciplinary network of scientists, clinicians, and community partners to examine the effects of environmental exposures that may predispose a woman to breast cancer throughout her life.

  7. Research Training in Biopsychosocial Breast Cancer Research

    National Research Council Canada - National Science Library

    Andrykowski, Michael

    2004-01-01

    ...) in biopsychosocial breast cancer (BC) research. During the 5-year project period, 6 predoctoral and 2 postdoctoral trainees were appointed to the training program and received training in biopsychosocial breast cancer research...

  8. Breast Cancer Epidemiology in Puerto Rico

    National Research Council Canada - National Science Library

    Nazario, Cruz M; Freudenheim, Jo

    2008-01-01

    This project has two mayor goals: to design and conduct a pilot case-control breast cancer study among Puerto Rican women, and to train and develop researchers in breast cancer at the University of Puerto Rico...

  9. Biomarkers for predicting complete debulking in ovarian cancer

    DEFF Research Database (Denmark)

    Fagö-Olsen, Carsten Lindberg; Ottesen, Bent; Christensen, Ib Jarle

    2014-01-01

    AIM: We aimed to construct and validate a model based on biomarkers to predict complete primary debulking surgery for ovarian cancer patients. PATIENTS AND METHODS: The study consisted of three parts: Part I: Biomarker data obtained from mass spectrometry, baseline data and, surgical outcome were.......64. CONCLUSION: Our validated model based on biomarkers was unable to predict surgical outcome for patients with ovarian cancer....

  10. Breast Cancer Screening in Denmark

    DEFF Research Database (Denmark)

    Jørgensen, Karsten Juhl; Gøtzsche, Peter C; Kalager, Mette

    2017-01-01

    Background: Effective breast cancer screening should detect early-stage cancer and prevent advanced disease. Objective: To assess the association between screening and the size of detected tumors and to estimate overdiagnosis (detection of tumors that would not become clinically relevant). Design......) and nonadvanced (≤20 mm) breast cancer tumors in screened and nonscreened women were measured. Two approaches were used to estimate the amount of overdiagnosis: comparing the incidence of advanced and nonadvanced tumors among women aged 50 to 84 years in screening and nonscreening areas; and comparing...... rate ratio, 1.49 [95% CI, 1.43 to 1.54]). The first estimation approach found that 271 invasive breast cancer tumors and 179 ductal carcinoma in situ (DCIS) lesions were overdiagnosed in 2010 (overdiagnosis rate of 24.4% [including DCIS] and 14.7% [excluding DCIS]). The second approach, which accounted...

  11. THERAPEUTIC OPTIONS FOR BREAST CANCER

    Directory of Open Access Journals (Sweden)

    Milena Georgescu

    2011-12-01

    Full Text Available Breast cancer remains a major public health problem, being the second cause of cancer death in women. There is a marked tendency to restrict the extension of surgical gesture, which directly leads to two different attitudes: radical surgery and conservative surgery, to which, at least in our country, there are still some delays. Prospective and retrospective studies have shown that, in 20 years, conservative and radical therapy had about the same rate of survival and disease-free interval, at least for stage I and II breast cancer, the only real counterargument against conservative surgery being that, in principle, the higher rate of recurrence local constraint can be solved by postoperative radiotherapy. Finally, the survival rate is the main parameter of evaluation, assessing the effectiveness of the treatment in breast cancer, and in all its other forms.

  12. Heavy Metal Exposure in Predicting Peripheral Neuropathy in Patients With Stage I-III Breast Cancer Undergoing Chemotherapy

    Science.gov (United States)

    2017-06-14

    Male Breast Cancer; Neurotoxicity; Peripheral Neuropathy; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

  13. Fulvestrant and Palbociclib in Treating Older Patients With Hormone Responsive Breast Cancer That Cannot Be Removed by Surgery

    Science.gov (United States)

    2016-09-21

    Estrogen Receptor and/or Progesterone Receptor Positive; HER2/Neu Negative; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

  14. Minocycline Hydrochloride in Reducing Chemotherapy Induced Depression and Anxiety in Patients With Stage I-III Breast Cancer

    Science.gov (United States)

    2017-08-07

    Anxiety Disorder; Depression; Recurrent Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

  15. Tumour infiltrating lymphocytes (TILs) in breast cancer during pregnancy.

    Science.gov (United States)

    Azim, Hatem A; Vingiani, Andrea; Peccatori, Fedro; Viale, Giuseppe; Loi, Sherene; Pruneri, Giancarlo

    2015-06-01

    Tumour infiltrating lymphocytes (TILs) is one of the most exciting breast cancer biomarkers, yet no data is available on its prevalence in tumours diagnosed during pregnancy. We evaluated the prevalence of TILs (stromal and intratumoural) in pregnant and non-pregnant young breast cancer patients. 11/116 (9.6%) of the non-pregnant and 2/86 (2.3%) pregnant patients had TILs ≥ 50% (p pregnancy. The low prevalence could reflect the state of low host immunity associated with pregnancy. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. A New Serum Biomarker for Lung Cancer - Transthyretin

    OpenAIRE

    Liu, Liyun; Sun, Suozhu; Liu, JiFu; WU, SHANSHAN; Songwei DAI; Wang, Xiaomin; Huang, Lingyun; Xueyuan XIAO; He, Dacheng

    2009-01-01

    Background and objective Lung cancer is the leading cause of cancer death worldwide and very few specific biomarkers could be used in clinical diagnosis at present. The aim of this study is to find novel potential serum biomarkers for lung cancer using Surface Enhanced Laser Desorption/Ionization (SELDI) technique. Methods Serumsample of 227 cases including 146 lung cancer, 13 pneumonia, 28 tuberculous pleurisy and 40 normal individuals were analyzed by CM10 chips. The candidate biomarkers we...

  17. Breast density does not impact the ability of Videssa® Breast to detect breast cancer in women under age 50.

    Directory of Open Access Journals (Sweden)

    David E Reese

    Full Text Available Breast density is associated with reduced imaging resolution in the detection of breast cancer. A biochemical approach that is not affected by density would provide an important tool to healthcare professionals who are managing women with dense breasts and suspicious imaging findings. Videssa® Breast is a combinatorial proteomic biomarker assay (CPBA, comprised of Serum Protein Biomarkers (SPB and Tumor Associated Autoantibodies (TAAb integrated with patient-specific clinical data to produce a diagnostic score that reliably detects breast cancer (BC as an adjunctive tool to imaging. The performance of Videssa® Breast was evaluated in the dense (a and b and non-dense (c and d groups in a population of n = 545 women under age 50. The sensitivity and specificity in the dense breast group were calculated to be 88.9% and 81.2%, respectively, and 92.3% and 86.6%, respectively, for the non-dense group. No significant differences were observed in the sensitivity (p = 1.0 or specificity (p = 0.18 between these groups. The NPV was 99.3% and 99.1% in non-dense and dense groups, respectively. Unlike imaging, Videssa® Breast does not appear to be impacted by breast density; it can effectively detect breast cancer in women with dense and non-dense breasts alike. Thus, Videssa® Breast provides a powerful tool for healthcare providers when women with dense breasts present with challenging imaging findings. In addition, Videssa® Breast provides assurance to women with dense breasts that they do not have breast cancer, reducing further anxiety in this higher risk patient population.

  18. Genetic susceptibility to breast cancer.

    Science.gov (United States)

    Mavaddat, Nasim; Antoniou, Antonis C; Easton, Douglas F; Garcia-Closas, Montserrat

    2010-06-01

    Genetic and lifestyle/environmental factors are implicated in the aetiology of breast cancer. This review summarizes the current state of knowledge on rare high penetrance mutations, as well as moderate and low-penetrance genetic variants implicated in breast cancer aetiology. We summarize recent discoveries from large collaborative efforts to combine data from candidate gene studies, and to conduct genome-wide association studies (GWAS), primarily in breast cancers in the general population. These findings are compared with results from collaborative efforts aiming to identify genetic modifiers in BRCA1 and BRCA2 carriers. Breast cancer is a heterogeneous disease, and tumours from BRCA1 and BRCA2 carriers display distinct pathological characteristics when compared with tumours unselected for family history. The relationship between genetic variants and pathological subtypes of breast cancer, and the implication of discoveries of novel genetic variants to risk prediction in BRCA1/2 mutation carriers and in populations unselected for mutation carrier status, are discussed. (c) 2010. Published by Elsevier B.V.

  19. Evaluate Risk/Benefit of Nab Paclitaxel in Combination With Gemcitabine and Carboplatin Compared to Gemcitabine and Carboplatin in Triple Negative Metastatic Breast Cancer (or Metastatic Triple Negative Breast Cancer)

    Science.gov (United States)

    2017-06-05

    Breast Tumor; Breast Cancer; Cancer of the Breast; Estrogen Receptor- Negative Breast Cancer; HER2- Negative Breast Cancer; Progesterone Receptor- Negative Breast Cancer; Recurrent Breast Cancer; Stage IV Breast Cancer; Triple-negative Breast Cancer; Triple-negative Metastatic Breast Cancer; Metastatic Breast Cancer

  20. Breast Cancer: Modelling and Detection

    OpenAIRE

    Gavaghan, D. J.; Brady, J. M.; Behrenbruch, C. P.; Highnam, R. P.; Maini, P. K.

    2002-01-01

    This paper reviews a number of the mathematical models used in cancer modelling and then chooses a specific cancer, breast carcinoma, to illustrate how the modelling can be used in aiding detection. We then discuss mathematical models that underpin mammographic image analysis, which complements models of tumour growth and facilitates diagnosis and treatment of cancer. Mammographic images are notoriously difficult to interpret, and we give an overview of the primary image enhancement technolog...

  1. Knowledge, awareness, and practices concerning breast cancer ...

    African Journals Online (AJOL)

    Background: Breast cancer is by far the most frequent cancer of women. However the preventive measures for such problem are probably less than expected. Objectives: The objectives of this study are to assess the breast cancer knowledge and awareness and factors associated with the practice of breast self examination ...

  2. Search for new breast cancer susceptibility genes

    NARCIS (Netherlands)

    Oldenburg, Rogier Abel

    2008-01-01

    This thesis describes the search for new high-risk breast cancer susceptibility genes by linkage analysis. To date 20-25% of familial breast cancer is explained by mutations in the high-risk BRCA1 and BRCA2 breast cancer susceptibility genes. For the remaining families the genetic etiology is

  3. Internet Use and Breast Cancer Survivors

    Science.gov (United States)

    Muhamad, Mazanah; Afshari, Mojgan; Mohamed, Nor Aini

    2011-01-01

    A survey was administered to 400 breast cancer survivors at hospitals and support group meetings in Peninsular Malaysia to explore their level of Internet use and factors related to the Internet use by breast cancer survivors. Findings of this study indicated that about 22.5% of breast cancer survivors used Internet to get information about breast…

  4. Pregnancy and abortion in breast cancer patients

    African Journals Online (AJOL)

    Breast cancer in pregnancy is by itself not an indication for abortion. We document the case histories of 2 patients with breast cancer (recurrent or advanced) who elected to carry pregnancies to term. Pregnancy concurrent with or subsequent to breast cancer is not associated with a worse prognosis than would be observed ...

  5. Dermatologic radiotherapy and breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Goldschmidt, H.; Gorson, R.O.; Lassen, M.

    1982-03-01

    This study was set up to provide quantitative data to evaluate unsubstantiated claims that improper dermatologic radiation techniques may cause breast cancer. A thin mylar window ionization rate meter placed at the location of the right breast of an Alderson-RANDO anthropomorphic phantom was used to measure direct and scatter radiation reaching the female breast during radiotherapy of the facial region (as given for acne). The results indicate that scatter doses are very small; they are influenced by radiation quality and the use or nonuse of a treatment cone. Quantitative risk estimates show that the very small risk of breast cancer induction can be reduced even further by the use of proper radiation protection measures.

  6. Proteomic profiling of mammary carcinomas identifies C7orf24, a gamma-glutamyl cyclotransferase, as a potential cancer biomarker

    DEFF Research Database (Denmark)

    Gromov, Pavel; Gromova, Irina; Friis, Esbern

    2010-01-01

    Breast cancer is the leading cause of cancer deaths in women today and is the most common cancer (excluding skin cancers) among women in the Western world. Although cancers detected by screening mammography are significantly smaller than nonscreening ones, noninvasive biomarkers for detection...... found in other cancer types. Four of these were investigated in greater detail, and we found that a proportion of tumors (58% in cervical, 38% in lung, 72% in colon, and 46% in breast cancer) expressed C7orf24 at levels exceeding those seen in normal samples. The observed overexpression of this protein...... of breast cancer as early as possible are an urgent need as the risk of recurrence and subsequent death is closely related to the stage of the disease at the time of primary surgery. A set of 123 primary breast tumors and matched normal tissue was analyzed by two-dimensional (2D) gel electrophoresis...

  7. Growth Factor Receptors and Apoptosis Regulators: Signaling Pathways, Prognosis, Chemosensitivity and Treatment Outcomes of Breast Cancer

    Directory of Open Access Journals (Sweden)

    Siddik Sarkar

    2009-01-01

    Full Text Available Biomarkers of breast cancer are necessary for prognosis and prediction to chemotherapy. Prognostic biomarkers provide information regarding outcome irrespective of therapy, while predictive biomarkers provide information regarding response to therapy. Candidate prognostic biomarkers for breast cancers are growth factor receptors, steroid receptors, Ki-67, cyclins, urokinase plasminogen activator, p53, p21, pro- and anti-apoptotic factors, BRCA1 and BRCA2. But currently, the predictive markers are Estrogen and Progesterone receptors responding to endocrine therapy, and HER-2 responding to herceptin. But there are numerous breast cancer cases, where tamoxifen is ineffective even after estrogen receptor positivity. This lead to search of new prognostic and predictive markers and the number of potential markers is constantly increasing due to proteomics and genomics studies. However, most biomarkers individually have poor sensitivity or specificity, or other clinical value. It can be resolved by studying various biomarkers simultaneously, which will help in better prognosis and increasing sensitivity for chemotherapeutic agents. This review is focusing on growth factor receptors, apoptosis markers, signaling cascades, and their correlation with other associated biomarkers in breast cancers. As our knowledge regarding molecular biomarkers for breast cancer increases, prognostic indices will be developed that combine the predictive power of individual molecular biomarkers with specific clinical and pathologic factors. Rigorous comparison of these existing as well as emerging markers with current treatment selection is likely to see an escalation in an era of personalized medicines to ensure the breast cancer patients receive optimal treatment. This will also solve the treatment modalities and complications related to chemotherapeutic regimens.

  8. Mammographic density, MRI background parenchymal enhancement and breast cancer risk

    Science.gov (United States)

    Pike, M. C.; Pearce, C. L.

    2013-01-01

    Mammographic density (MD), representing connective and epithelial tissue (fibroglandular tissue, FGT) is a major risk factor for breast cancer. In an analysis of an autopsy series (Bartow SA, Pathak DR, Mettler FA. Radiographic microcalcification and parenchymal patterns as indicators of histologic “high-risk” benign breast disease. Cancer 1990; 66: 1721–1725, Bartow SA, Pathak DR, Mettler FA et al. Breast mammographic pattern: a concatenation of confounding and breast cancer risk factors. Am J Epidemiol 1995; 142: 813–819), MD was found to be strongly correlated with the collagen and epithelial content of the breast (Li T, Sun L, Miller N et al. The association of measured breast tissue characteristics with MD and other risk factors for breast cancer. Cancer Epidemiol Biomarkers Prev 2005; 14: 343–349), and another report showed that breast epithelium was highly concentrated in the areas of collagen concentration (Hawes D, Downey S, Pearce CL et al. Dense breast stromal tissue shows greatly increased concentration of breast epithelium but no increase in its proliferative activity. Breast Cancer Res 2006; 8: R24). Collagen comprises the overwhelming majority of the FGT, occupying an area on the slides obtained from the autopsy series some 15 times the area of glandular tissue. The relationship of MD with breast cancer risk appears likely to be due to a major extent to increasing epithelial cell numbers with increasing MD. FGT is also seen in breast magnetic resonance imaging (breast MRI) and, as expected, it has been shown that this measure of FGT (MRI-FGT) is highly correlated with MD. A contrast-enhanced breast MRI shows that normal FGT ‘enhances’ (background parenchymal enhancement, BPE) after contrast agent is administered(Morris EA. Diagnostic breast MR imaging: current status and future directions. Radiol Clin North Am 2007; 45: 863–880, vii., Kuhl C. The current status of breast MR imaging. Part I. Choice of technique, image interpretation

  9. Mammographic density, MRI background parenchymal enhancement and breast cancer risk.

    Science.gov (United States)

    Pike, M C; Pearce, C L

    2013-11-01

    Mammographic density (MD), representing connective and epithelial tissue (fibroglandular tissue, FGT) is a major risk factor for breast cancer. In an analysis of an autopsy series (Bartow SA, Pathak DR, Mettler FA. Radiographic microcalcification and parenchymal patterns as indicators of histologic "high-risk" benign breast disease. Cancer 1990; 66: 1721-1725, Bartow SA, Pathak DR, Mettler FA et al. Breast mammographic pattern: a concatenation of confounding and breast cancer risk factors. Am J Epidemiol 1995; 142: 813-819), MD was found to be strongly correlated with the collagen and epithelial content of the breast (Li T, Sun L, Miller N et al. The association of measured breast tissue characteristics with MD and other risk factors for breast cancer. Cancer Epidemiol Biomarkers Prev 2005; 14: 343-349), and another report showed that breast epithelium was highly concentrated in the areas of collagen concentration (Hawes D, Downey S, Pearce CL et al. Dense breast stromal tissue shows greatly increased concentration of breast epithelium but no increase in its proliferative activity. Breast Cancer Res 2006; 8: R24). Collagen comprises the overwhelming majority of the FGT, occupying an area on the slides obtained from the autopsy series some 15 times the area of glandular tissue. The relationship of MD with breast cancer risk appears likely to be due to a major extent to increasing epithelial cell numbers with increasing MD. FGT is also seen in breast magnetic resonance imaging (breast MRI) and, as expected, it has been shown that this measure of FGT (MRI-FGT) is highly correlated with MD. A contrast-enhanced breast MRI shows that normal FGT 'enhances' (background parenchymal enhancement, BPE) after contrast agent is administered(Morris EA. Diagnostic breast MR imaging: current status and future directions. Radiol Clin North Am 2007; 45: 863-880, vii., Kuhl C. The current status of breast MR imaging. Part I. Choice of technique, image interpretation, diagnostic

  10. Trastuzumab Emtansine in Treating Older Patients With Human Epidermal Growth Factor Receptor 2-Positive Stage I-III Breast Cancer

    Science.gov (United States)

    2018-02-01

    Estrogen Receptor Status; HER2 Positive Breast Carcinoma; Progesterone Receptor Status; Stage I Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage III Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

  11. Multiparametric Breast MRI of Breast Cancer

    Science.gov (United States)

    Rahbar, Habib; Partridge, Savannah C.

    2015-01-01

    Synopsis Breast MRI has increased in popularity over the past two decades due to evidence for its high sensitivity for cancer detection. Current clinical MRI approaches rely on the use of a dynamic contrast enhanced (DCE-MRI) acquisition that facilitates morphologic and semi-quantitative kinetic assessments of breast lesions. The use of more functional and quantitative parameters, such as pharmacokinetic features from high temporal resolution DCE-MRI, apparent diffusion coefficient (ADC) and intravoxel incoherent motion (IVIM) on diffusion weighted MRI, and choline concentrations on MR spectroscopy, hold promise to broaden the utility of MRI and improve its specificity. However, due to wide variations in approach among centers for measuring these parameters and the considerable technical challenges, robust multicenter data supporting their routine use is not yet available, limiting current applications of many of these tools to research purposes. PMID:26613883

  12. [Breast cancer: new therapeutic strategies].

    Science.gov (United States)

    Espie, M

    1998-12-12

    NEED FOR NEW CHEMOTHERAPY AGENTS: Metastasic breast cancer is an excellent model for studying anticancer agents: chemotherapy or hormonotherapy or compounds modifying the organism's response. If no adjuvant treatment is given after locoregional treatment of breast cancer, metastasis will develop within 10 years in 30% of the patients free of initial nodal invasion and within 5 years in 50% of the patients with initial nodal invasion. ADJUVANT TREATMENTS: Hormonotherapy and chemotherapy reduce mortality due to breast cancer by 10%. New adjuvant agents have been recently introduced. Taxans (docetaxel, paclitaxel) are the most active molecules since antracyclines. New aromataase inhibitors include letrozole and anastrozole. Their efficacy has been demonstrated in phase II and phase III trials, allowing their experimentation as adjuvant treatments.

  13. Breast cancer: demands of illness.

    Science.gov (United States)

    Loveys, B J; Klaich, K

    1991-01-01

    This study explores the qualitative experience of illness demands from the woman's own perspective by asking, "What is the impact of breast cancer on the daily lives of women of childbearing age?" Semistructured interviews with 79 women newly diagnosed with breast cancer were transcribed and analyzed to discern illness demands. Content analysis yielded 14 domains of illness demands: treatment issues, change in life context or perspective, acceptance of the illness, social interaction or support, physical changes, reconstructing the self, uncertainty, loss, making comparisons, acquiring new knowledge, making choices, mortality issues, financial or occupational concerns, and making a contribution. Illness demands are experienced in every aspect of a woman's life, including her identity, daily routines, family and social experience, and her perception of the past, present, and future. This study details in the women's own language the considerable adjustments brought on by a diagnosis of breast cancer.

  14. Breast cancer circulating tumor cells

    Directory of Open Access Journals (Sweden)

    Maria Joao Carvalho

    2011-12-01

    Full Text Available Metastasization of breast cancer involves various mechanisms responsible for progression from invasive lesion to dissemination in distant organs. Regional lymph node metastasization was considered an initial step in this process, but it is now recognized that hematogenous dissemination is a deviation from lymphatic circulation. The detection of circulating tumor cells (CTC is an aim in several oncology areas. For this purpose, several techniques have been used to detect CTC, including the use of antibodies and techniques with nucleic acids. This study reviews the published studies considering the detection of breast cancer CTC. There are focused the difficulties in identifying a CTC in a heterogeneous population, the handling of the sample, criteria of positivity, analytical techniques, and specific markers. There are systematized various specific markers of breast cancer cells also the problems with false positive results. Finally, we hypothesize clinical applications either as a prognostic marker or as a therapeutic response monitor.

  15. Risk-based Breast Cancer Screening: Implications of Breast Density.

    Science.gov (United States)

    Lee, Christoph I; Chen, Linda E; Elmore, Joann G

    2017-07-01

    The approach to breast cancer screening has changed over time from a general approach to a more personalized, risk-based approach. Women with dense breasts, one of the most prevalent risk factors, are now being informed that they are at increased risk of developing breast cancer and should consider supplemental screening beyond mammography. This article reviews the current evidence regarding the impact of breast density relative to other known risk factors, the evidence regarding supplemental screening for women with dense breasts, supplemental screening options, and recommendations for physicians having shared decision-making discussions with women who have dense breasts. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Reconstruction for breast cancer in a nutshell.

    Science.gov (United States)

    Harmer, Victoria

    Breast cancer is a disease many will experience. Depending on the size of the cancer, the size of the host breast, and whether it is multi-focal, a mastectomy may be recommended as part of the treatment. If this is the case, an immediate breast reconstruction may be offered. This article will describe the three main types of breast reconstruction and discuss pertinent issues regarding this, including complications, surgery to the other (contraleteral) breast and potential psychological implications of this surgery.

  17. Genetic heterogeneity in breast cancer susceptibility.

    Science.gov (United States)

    Andersen, T I

    1996-01-01

    Approximately 20% of breast cancer patients have a family history of the disease, and in one-fourth of these cases breast cancer appears to be inherited as an autosomally dominant trait. Five genes and gene regions involved in breast cancer susceptibility have been uncovered. Germ-line mutations in the recently cloned BRCA1 gene at 17q21 is considered to be responsible for the disease in a majority of the breast-ovarian cancer families and in 40-45% of the site-specific breast cancer families, but appears not to be involved in families with both male and female breast cancer cases. The BRCA2 locus at 13q12-q13 appears to be involved in 40-45% of the site-specific breast cancer families, and in most of the families with affected males. The gene located in this region, however, does not seem to confer susceptibility to ovarian cancer. The TP53 gene is involved in breast cancer development in the Li-Fraumeni syndrome and Li-Fraumeni syndrom-like families, whereas germ-line mutations in the androgen receptor (AR) gene is present in a subset of male breast cancers. Furthermore, females who are obligate carriers of ataxia telangiectasia (AT) have a 4-12 times relative risk of developing breast cancer as compared with the general female population, indicating that germ-line mutations in AT also confer susceptibility to breast cancer.

  18. Nanoparticle-based Paclitaxel vs Solvent-based Paclitaxel as Part of Neoadjuvant Chemotherapy for Early Breast Cancer (GeparSepto)

    Science.gov (United States)

    2016-10-11

    Tubular Breast Cancer Stage II; Mucinous Breast Cancer Stage II; Breast Cancer Female NOS; Invasive Ductal Breast Cancer; Tubular Breast Cancer Stage III; HER-2 Positive Breast Cancer; Inflammatory Breast Cancer Stage IV; Inflammatory Breast Cancer

  19. Cancer therapy trials employing level-of-evidence-1 disease forecast cancer biomarkers uPA and its inhibitor PAI-1

    DEFF Research Database (Denmark)

    Schmitt, Manfred; Harbeck, Nadia; Brünner, Nils

    2011-01-01

    conducted in early breast cancer to demonstrate the prognostic and predictive value for this malignancy. As a result of these investigations, uPA and PAI-1 have reached the highest level of clinical evidence, level of evidence 1. This article sheds light on the current status of major clinical Phase II......-size synthetic peptide (Å6) is tested in advanced ovarian cancer patients.......Clinical research on cancer biomarkers is essential in understanding recent discoveries in cancer biology and heterogeneity of the cancer disease. However, there are only a few examples of clinically useful studies that have identified cancer biomarkers with clinical benefit. Urokinase...

  20. Antiangiogenic therapy for breast cancer

    DEFF Research Database (Denmark)

    Nielsen, D.L.; Andersson, M.; Andersen, Jon Alexander Lykkegaard

    2010-01-01

    and optimal use of these agents for the treatment of breast cancer. Currently, the most promising approach has been the use of bevacizumab, a humanized monoclonal antibody directed against the most potent pro-angiogenic factor, vascular endothelial growth factor (VEGF). Small molecular inhibitors of VEGF...... tyrosine kinase activity, such as sorafenib, appear promising. While, the role of sunitinib and inhibitors of mammalian target of rapamycin (mTOR) in breast cancer has to be defined. Several unanswered questions remain, such as choice of drug(s), optimal duration of therapy and patient selection criteria...

  1. Paclitaxel (Taxol) in breast cancer.

    Science.gov (United States)

    Arbuck, S G; Dorr, A; Friedman, M A

    1994-02-01

    Paclitaxel (Taxol) is a diterpine plant compound that was isolated initially from the bark of the western yew tree, Taxus brevifolia, but can now be produced by semisynthesis from a renewable source. Paclitaxel is the first new agent in the past decade to have confirmed single agent activity in breast cancer in excess of 50%. A 28% response rate has been reported in doxorubicin-refractory patients. Ongoing studies include attempts to combine paclitaxel with other drugs used for breast cancer treatment and with radiation.

  2. Quality indicators for breast cancer

    DEFF Research Database (Denmark)

    Poortmans, Philip; Aznar, Marianne; Bartelink, Harry

    2012-01-01

    Radiation therapy for breast cancer has considerably changed over the years, from simple simulator-based 2-dimensional techniques to sophisticated image-guided individualized treatments, with maximally protected normal structures. This has led to a substantial improvement in the outcome of breast...... cancer patients in terms of disease control, survival, and quality of life. This progress is based on clinical research and paralleled by progress in delivering sophisticated radiation treatment. Clinical trials resulted in identifying patients groups who will benefit from radiation treatment. They also...

  3. Overdiagnosis in breast cancer screening

    DEFF Research Database (Denmark)

    Lynge, Elsebeth; Beau, Anna-Belle; Christiansen, Peer

    2017-01-01

    Overdiagnosis in breast cancer screening is an important issue. A recent study from Denmark concluded that one in three breast cancers diagnosed in screening areas in women aged 50-69 years were overdiagnosed. The purpose of this short communication was to disentangle the study's methodology...... estimate of overdiagnosis. Screening affects cohorts of screened women. Danish registers allow very accurate mapping of the fate of every woman. We should be past the phase where studies of overdiagnosis are based on the fixed age groups from routine statistics....

  4. An update on inflammatory breast cancer

    Directory of Open Access Journals (Sweden)

    P. Thapaliya

    2011-12-01

    Full Text Available Inflammatory breast cancer is one of the most aggressive forms of breast cancer. Once considered to be a uniformly fatal disease, treatment of this entity has evolved significantly over the last two decades. In this article, we review the epidemiology, pathology, biologic underpinnings, radiologic advances, and treatment modalities for inflammatory breast cancer. Updates in surgical therapy, medical oncologic therapy and radiation therapy are reviewed. Emphasis is on cutting edge information regarding inflammatory breast cancer. The management of inflammatory breast cancer is best served by a multidisciplinary team. Continued research into molecular pathways and potential targets is imperative. Future clinical trials should include evaluation of conventional therapy with targeted therapies.

  5. Breast cancer epidemiology and risk factors

    Energy Technology Data Exchange (ETDEWEB)

    Broeders, M. J. M.; Verbeek, A. L. M. [Nijmegen, Univ. (Netherlands). Dept. of Epidemiology

    1997-09-01

    Breast cancer is the most common malignancy among women in the Western society. Over the past decades it has become apparent that breast cancer incidence rates are increasing steadily, whereas the mortality rates for breast cancer have remained relatively constant. Information through the media on this rising number of cases has increased breast health awareness but has also introduced anxiety in the female population. This combination of factors has made the need for prevention of breast cancer an urgent matter. Breast cancer does not seem to be a single disease entity. A specific etiologic factor may therefore have more influence on one form may therefore have more influence on one form of breast cancer than another. So far though, as shown in their summary of current knowledge on established and dubious risk factors, no risk factors have been identified that can explain a major part of the incidence. Efforts to identify other ways for primary prevention have also been discouraging, even though breast cancer is one of the most investigated tumours world-wide. Thus, at this point i time, the most important strategy to reduce breast cancer mortality is early detection through individual counselling and organised breast screening programs. The recent isolation of breast cancer susceptibility genes may introduce new ways to reduce the risk of breast cancer in a small subset of women.

  6. Ten Years of Tamoxifen Reduces Breast Cancer Recurrences, Improves Survival

    Science.gov (United States)

    ... Years of Tamoxifen Reduces Breast Cancer Recurrences, Improves Survival For some women with breast cancer , taking adjuvant ... Years of Tamoxifen Reduces Breast Cancer Recurrences, Improves Survival was originally published by the National Cancer Institute.” ...

  7. Ultrasound screening of contralateral breast after surgery for breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Seung Ja [Department of Radiology, Seoul Metropolitan Government Seoul National University, Boramae Medical Center (Korea, Republic of); Chung, Se-Yeong; Chang, Jung Min; Cho, Nariya [Department of Radiology, Seoul National University Hospital (Korea, Republic of); Han, Wonshik [Department of Surgery, Seoul National University Hospital (Korea, Republic of); Moon, Woo Kyung, E-mail: moonwk@snu.ac.kr [Department of Radiology, Seoul National University Hospital (Korea, Republic of)

    2015-01-15

    Highlights: • The addition of supplemental US to mammography depicted additional 5.0 cancers per 1000 postoperative women. • Positive biopsy rate of mammography-detected lesions was 66.7% (4 of 6) and that of US-detected lesions was 40.0% (6 of 15). • US can be helpful to detect mammographically occult breast cancer in the contralateral breast in women with previous history of cancer and dense breast. - Abstract: Objective: To determine whether supplemental screening ultrasound (US) to mammography could improve cancer detection rate of the contralateral breast in patients with a personal history of breast cancer and dense breasts. Materials and methods: During a one-year study period, 1314 screening patients with a personal history of breast cancer and dense breasts simultaneously underwent mammography and breast US. BI-RADS categories were given for mammography or US-detected lesions in the contralateral breast. The reference standard was histology and/or 1-year imaging follow-up, and the cancer rate according to BI-RADS categories and cancer detection rate and positive biopsy rate according to detection modality were analyzed. Results: Of 1314 patients, 84 patients (6.4%) were categorized as category 3 with one interval cancer and one cancer which was upgraded to category 4A after 6-month follow-up US (2.5% cancer rate, 95% CIs 1.5–9.1%). Fifteen patients (1.1%) had category 4A or 4B lesions in the contralateral breast. Four lesions were detected on mammography (two lesions were also visible on US) and 11 lesions were detected on US and 5 cancers were confirmed (33.3%, 95% CIs 15.0–58.5%). Six patients (0.5%) had category 4C lesions, 2 detected on mammography and 4 on US and 4 cancers were confirmed (66.7%, 95% CIs 29.6–90.8%). No lesions were categorized as category 5 in the contralateral breast. Cancer detection rate by mammography was 3.3 per 1000 patients and that by US was 5.0 per 1000 patients, therefore overall cancer detection rate by

  8. Interactive Gentle Yoga in Improving Quality of Life in Patients With Stage I-III Breast Cancer Undergoing Radiation Therapy

    Science.gov (United States)

    2017-07-28

    Anxiety Disorder; Depression; Ductal Breast Carcinoma in Situ; Fatigue; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

  9. NUCKS overexpression in breast cancer

    Directory of Open Access Journals (Sweden)

    Kittas Christos

    2009-08-01

    Full Text Available Abstract Background NUCKS (Nuclear, Casein Kinase and Cyclin-dependent Kinase Substrate is a nuclear, DNA-binding and highly phosphorylated protein. A number of reports show that NUCKS is highly expressed on the level of mRNA in several human cancers, including breast cancer. In this work, NUCKS expression on both RNA and protein levels was studied in breast tissue biopsies consisted of invasive carcinomas, intraductal proliferative lesions, benign epithelial proliferations and fibroadenomas, as well as in primary cultures derived from the above biopsies. Specifically, in order to evaluate the level of NUCKS protein in correlation with the histopathological features of breast disease, immunohistochemistry was employed on paraffin sections of breast biopsies of the above types. In addition, NUCKS expression was studied by means of Reverse Transcription PCR (RT-PCR, real-time PCR (qRT-PCR and Western immunoblot analyses in the primary cell cultures developed from the same biopsies. Results The immunohistochemical Results showed intense NUCKS staining mostly in grade I and II breast carcinomas compared to normal tissues. Furthermore, NUCKS was moderate expressed in benign epithelial proliferations, such as adenosis and sclerosing adenosis, and highly expressed in intraductal lesions, specifically in ductal carcinomas in situ (DCIS. It is worth noting that all the fibroadenoma tissues examined were negative for NUCKS staining. RT-PCR and qRT-PCR showed an increase of NUCKS expression in cells derived from primary cultures of proliferative lesions and cancerous tissues compared to the ones derived from normal breast tissues and fibroadenomas. This increase was also confirmed by Western immunoblot analysis. Although NUCKS is a cell cycle related protein, its expression does not correlate with Ki67 expression, neither in tissue sections nor in primary cell cultures. Conclusion The results show overexpression of the NUCKS protein in a number of non

  10. Delayed breast reconstruction with implants after invasive breast cancer does not impair prognosis

    DEFF Research Database (Denmark)

    Holmich, L.R.; During, M.; Henriksen, T.F.

    2008-01-01

    We investigated if delayed breast implant reconstruction after breast cancer impairs prognosis. Using data from the Danish Breast Cancer Cooperative Group register, we identified all women......We investigated if delayed breast implant reconstruction after breast cancer impairs prognosis. Using data from the Danish Breast Cancer Cooperative Group register, we identified all women...

  11. Association of Pancreatic Cancer Susceptibility Variants with Risk of Breast Cancer in Women of European and African Ancestry.

    Science.gov (United States)

    Wang, Shengfeng; Zheng, Yonglan; Ogundiran, Temidayo O; Ojengbede, Oladosu; Zheng, Wei; Nathanson, Katherine L; Nemesure, Barbara; Ambs, Stefan; Olopade, Olufunmilayo I; Huo, Dezheng

    2018-01-01

    Background: Pancreatic cancer mutation signatures closely resemble breast cancer, suggesting that both cancers may have common predisposition mechanisms that may include commonly inherited SNPs. Methods: We examined 23 genetic variants known to be associated with pancreatic cancer as breast cancer risk factors in the Root genome-wide association study (GWAS; 1,657 cases and 2,029 controls of African diaspora) and GAME-ON/DRIVE GWAS (16,003 cases and 41,335 controls of European ancestry). Results: None of the pancreatic cancer susceptibility variants were individually associated with breast cancer risk after adjustment for multiple testing (at α = 0.002) in the two populations. In Root GWAS, a change by one SD in the polygenic risk score (PRS) was not significantly associated with breast cancer. In addition, we did not observe a trend in the relationship between PRS percentiles and breast cancer risk. Conclusions: The association between reported pancreatic cancer genetic susceptibility variants and breast cancer development in women of African or European ancestry is likely weak, if it does exist. Impact: Known GWAS-derived susceptibility variants of pancreatic cancer do not explain its shared genetic etiology with breast cancer. Cancer Epidemiol Biomarkers Prev; 27(1); 116-8. ©2017 AACR . ©2017 American Association for Cancer Research.

  12. Prostate cancer biomarkers: Are we hitting the mark?

    Directory of Open Access Journals (Sweden)

    Shannon McGrath

    2016-12-01

    Conclusion: The accurate diagnosis and risk stratification of prostate cancer is critical to ensure appropriate intervention. The development of non-invasive biomarkers can add to the information provided by current screening practices and allows for individualised risk stratification of patients. The use of these biomarkers appears to increase the sensitivity and specificity of diagnosis of prostate cancer. Further studies are necessary to define the appropriate use and time points of each biomarker and their effect on the management algorithm of prostate cancer.

  13. Low penetrance breast cancer susceptibility loci are associated with specific breast tumor subtypes: findings from the Breast Cancer Association Consortium

    National Research Council Canada - National Science Library

    Broeks, A; Schmidt, M.K; Sherman, M.E; Couch, F.J; Hopper, J.L; Dite, G.S; Apicella, C; Smith, L.D; Hammet, F; Southey, M.C; Veer, L.J. van 't; Groot, R. de; Smit, V.T; Fasching, P.A; Beckmann, M.W; Jud, S; Ekici, A.B; Hartmann, A; Hein, A; Schulz-Wendtland, R; Burwinkel, B; Marme, F; Schneeweiss, A; Sinn, H.P; Sohn, C; Tchatchou, S; Bojesen, S.E; Nordestgaard, B.G; Flyger, H; Orsted, D.D; Kaur-Knudsen, D; Milne, R.L; Perez, J.I; Zamora, P; Roiguez, P.M; Benitez, J; Brauch, H; Justenhoven, C; Ko, Y.D; Hamann, U; Fischer, H.P; Bruning, T; Pesch, B; Chang-Claude, J; Wang-Gohrke, S; Bremer, M; Karstens, J.H; Hillemanns, P; Dork, T; Nevanlinna, H.A; Heikkinen, T; Heikkila, P; Blomqvist, C; Aittomaki, K; Aaltonen, K; Lindblom, A; Margolin, S; Mannermaa, A; Kosma, V.M; Kauppinen, J.M; Kataja, V; Auvinen, P; Eskelinen, M; Soini, Y; Chenevix-Trench, G; Spurdle, A.B; Beesley, J; Chen, X; Holland, H; Lambrechts, D; Claes, B; Vandorpe, T; Neven, P; Wildiers, H; Flesch-Janys, D; Hein, R; Loning, T; Kosel, M; Fredericksen, Z.S; Wang, X; Giles, G.G; Baglietto, L; Severi, G; McLean, C; Haiman, C.A; Henderson, B.E; Marchand, L. le; Kolonel, L.N; Alnaes, G.G; Kristensen, V; Borresen-Dale, A.L; Hunter, D.J; Hankinson, S.E; Anulis, I.L; Mulligan, A.M; O'Malley, F.P; Devilee, P; Huijts, P.E; Tollenaar, R.A.E.M; Asperen, C.J. van

    2011-01-01

    .... We investigated breast cancer risk associations of eight susceptibility loci identified in GWAS and two putative susceptibility loci in candidate genes in relation to specific breast tumor subtypes...

  14. Alcohol and breast cancer: the mechanisms explained.

    Science.gov (United States)

    Al-Sader, Hassen; Abdul-Jabar, Hani; Allawi, Zahra; Haba, Yasser

    2009-08-01

    Breast cancer is a leading cause of death amongst women, several studies have shown significant association between alcohol consumption and breast cancer. The aim of this overview is to highlight some of the mechanisms by which alcohol consumption could increase the risk of developing breast cancer. Using online Medline search engine, article containing details about mechanisms which explain the link between alcohol and breast cancer were examined. A number of mechanisms were found by which alcohol could increase the risk of breast cancer, alcohol's interaction and effect on oestrogen secretion; number of oestrogen receptors; the generation of acetaldehyde and hydroxyl free radicals; cells migration and metastasis; secretion of IGF1 and interaction with HRT and folate metabolism. In conclusion, it is essential for clinicians to understand these mechanisms and inform patients of the link between alcohol and breast cancer. Breast cancer; Alcohol; Mechanisms.

  15. Mechanisms involved in breast cancer liver metastasis.

    Science.gov (United States)

    Ma, Rui; Feng, Yili; Lin, Shuang; Chen, Jiang; Lin, Hui; Liang, Xiao; Zheng, Heming; Cai, Xiujun

    2015-02-15

    Liver metastasis is a frequent occurrence in patients with breast cancer; however, the available treatments are limited and ineffective. While liver-specific homing of breast cancer cells is an important feature of metastasis, the formation of liver metastases is not random. Indeed, breast cancer cell factors contribute to the liver microenvironment. Major breakthroughs have been achieved recently in understanding breast cancer liver metastasis (BCLM). The process of liver metastasis consists of multiple steps and involves various factors from breast cancer cells and the liver microenvironment. A further understanding of the roles of breast cancer cells and the liver microenvironment is crucial to guide future work in clinical treatments. In this review we discuss the contribution of breast cancer cells and the liver microenvironment to liver metastasis, with the aim to improve therapeutic efficacy for patients with BCLM.

  16. Biomarkers of depression in cancer patients.

    Science.gov (United States)

    Jehn, Christian Friedrich; Kuehnhardt, Dagmar; Bartholomae, Andrea; Pfeiffer, Sebastian; Krebs, Michael; Regierer, Anne Constanze; Schmid, Peter; Possinger, Kurt; Flath, Bernd Christian

    2006-12-01

    Inflammation and perturbation of the hypothalamic-pituitary-adrenal (HPA) axis function appears to play a putative role in the etiology of depression. Patients with metastatic cancer demonstrate elevated prevalence rates for depression. The objective of the current study was to illustrate the efficacy of interleukin-6 (IL-6) and HPA axis function as adjuncts to support the diagnosis of depression in cancer patients. Plasma concentrations of IL-6 and cortisol were measured in 114 cancer patients with and without depression. The relative diurnal variation of cortisol (cortisol VAR), expressed as a percentage, was calculated. Receiver operating characteristics analysis was performed. Depression was associated with increased plasma concentrations of IL-6 (18.7 pg/mL vs. 2.7 pg/mL; P < .001) and higher cortisol concentrations at 8 AM and 8 PM. The relative cortisol VAR (11.7% vs. 60.6%, respectively; P < .001) was found to be decreased in cancer patients with depression, indicating a disturbed circadian function of the HPA axis. As a biomarker of depression, IL-6 yielded at a cutoff value of 10.6 pg/mL, a sensitivity of 79%, and a specificity of 87% (area under the curve [AUC] = 0.86; 95% confidence interval [95% CI], 0.78-0.94), whereas cortisol VAR demonstrated a sensitivity of 81% and a specificity of 88% (AUC = 0.85; 95% CI, 0.74-0.97) at a cutoff value of 33.5%. Depression is associated with increased plasma IL-6 concentrations in patients with cancer. These patients demonstrate a dysfunction of the HPA-axis, characterized by a decreased diurnal variation of cortisol. The high sensitivity and specificity of these parameters biomarkers of depression make IL-6 and cortisol VAR helpful tools in the diagnosis of depression in patients with cancer. (c) 2006 American Cancer Society.

  17. Hydrophobic Fractionation Enhances Novel Protein Detection by Mass Spectrometry in Triple Negative Breast Cancer.

    Science.gov (United States)

    Lu, Ming; Whitelegge, Julian P; Whelan, Stephen A; He, Jianbo; Saxton, Romaine E; Faull, Kym F; Chang, Helena R

    2010-01-22

    It is widely believed that discovery of specific, sensitive and reliable tumor biomarkers can improve the treatment of cancer. The goal of this study was to develop a novel fractionation protocol targeting hydrophobic proteins as possible cancer cell membrane biomarkers. Hydrophobic proteins of breast cancer tissues and cell lines were enriched by polymeric reverse phase columns. The retained proteins were eluted and digested for peptide identification by nano-liquid chromatography with tandem mass spectrometry using a hybrid linear ion-trap Orbitrap.Hundreds of proteins were identified from each of these three specimens: tumors, normal breast tissue, and breast cancer cell lines. Many of the identified proteins defined key cellular functions. Protein profiles of cancer and normal tissues from the same patient were systematically examined and compared. Stem cell markers were overexpressed in triple negative breast cancer (TNBC) compared with non-TNBC samples. Because breast cancer stem cells are known to be resistant to radiation and chemotherapy, and can be the source of metastasis frequently seen in patients with TNBC, our study may provide evidence of molecules promoting the aggressiveness of TNBC.The initial results obtained using a combination of hydrophobic fractionation and nano-LC mass spectrometry analysis of these proteins appear promising in the discovery of potential cancer biomarkers. When sufficiently refined, this approach may prove useful for early detection and better treatment of breast cancer.

  18. Hydrophobic Fractionation Enhances Novel Protein Detection by Mass Spectrometry in Triple Negative Breast Cancer

    Science.gov (United States)

    Lu, Ming; Whitelegge, Julian P.; Whelan, Stephen A.; He, Jianbo; Saxton, Romaine E.; Faull, Kym F.; Chang, Helena R.

    2010-01-01

    It is widely believed that discovery of specific, sensitive and reliable tumor biomarkers can improve the treatment of cancer. The goal of this study was to develop a novel fractionation protocol targeting hydrophobic proteins as possible cancer cell membrane biomarkers. Hydrophobic proteins of breast cancer tissues and cell lines were enriched by polymeric reverse phase columns. The retained proteins were eluted and digested for peptide identification by nano-liquid chromatography with tandem mass spectrometry using a hybrid linear ion-trap Orbitrap. Hundreds of proteins were identified from each of these three specimens: tumors, normal breast tissue, and breast cancer cell lines. Many of the identified proteins defined key cellular functions. Protein profiles of cancer and normal tissues from the same patient were systematically examined and compared. Stem cell markers were overexpressed in triple negative breast cancer (TNBC) compared with non-TNBC samples. Because breast cancer stem cells are known to be resistant to radiation and chemotherapy, and can be the source of metastasis frequently seen in patients with TNBC, our study may provide evidence of molecules promoting the aggressiveness of TNBC. The initial results obtained using a combination of hydrophobic fractionation and nano-LC mass spectrometry analysis of these proteins appear promising in the discovery of potential cancer biomarkers. When sufficiently refined, this approach may prove useful for early detection and better treatment of breast cancer. PMID:20596302

  19. Human papilloma viruses (HPV and breast cancer.

    Directory of Open Access Journals (Sweden)

    James Sutherland Lawson

    2015-12-01

    Full Text Available Purpose: Human papillomaviruses (HPV may have a role in some breast cancers. The purpose of this study is to fill important gaps in the evidence. These gaps are: (i confirmation of the presence of high risk for cancer HPVs in breast cancers, (ii evidence of HPV infections in benign breast tissues prior to the development of HPV positive breast cancer in the same patients, (iii evidence that HPVs are biologically active and not harmless passengers in breast cancer.Methods: RNA-seq data from The Cancer Genome Atlas (TCGA was used to identify HPV RNA sequences in breast cancers. We also conducted a retrospective cohort study based on polymerase chain reaction (PCR analyses to identify HPVs in archival specimens from Australian women with benign breast biopsies who later developed breast cancer. To assess whether HPVs in breast cancer were biologically active, the expression of the oncogenic protein HPV E7 was assessed by immunohistochemistry (IHC.Results: Thirty (3.5% low risk and 20 (2.3% high risk HPV types were identified in 855 breast cancers from the TCGA data base. The high risk types were HPV 18 (48%, HPV 113 (24%, HPV 16 (10%, HPV 52 (10%. Data from the PCR cohort study, indicated that HPV type 18 was the most common type identified in breast cancer specimens (55% of 40 breast cancer specimens followed by HPV 16 (13%. The same HPV type was identified in both the benign and subsequent breast cancer in 15 patients. HPV E7 proteins were identified in 72% of benign breast specimens and 59% of invasive breast cancer specimens.Conclusions: There were 4 observations of particular interest: (i confirmation by both NGS and PCR of the presence of high risk HPV gene sequences in breast cancers, (ii a correlation between high risk HPV in benign breast specimens and subsequent HPV positive breast cancer in the same patient, (iii HPVs in breast cancer are likely to be biologically active (as shown by transcription of HPV DNA to RNA plus the expression of

  20. Caloric Restriction in Treating Patients With Stage 0-I Breast Cancer Undergoing Surgery and Radiation Therapy

    Science.gov (United States)

    2017-09-25

    Ductal Breast Carcinoma in Situ; Invasive Ductal Breast Carcinoma; Invasive Lobular Breast Carcinoma; Lobular Breast Carcinoma in Situ; Recurrent Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer

  1. Antiangiogenic therapy for breast cancer

    DEFF Research Database (Denmark)

    Nielsen, D.L.; Andersson, M.; Andersen, Jon Alexander Lykkegaard

    2010-01-01

    and optimal use of these agents for the treatment of breast cancer. Currently, the most promising approach has been the use of bevacizumab, a humanized monoclonal antibody directed against the most potent pro-angiogenic factor, vascular endothelial growth factor (VEGF). Small molecular inhibitors of VEGF...... tyrosine kinase activity, such as sorafenib, appear promising. While, the role of sunitinib and inhibitors of mammalian target of rapamycin (mTOR) in breast cancer has to be defined. Several unanswered questions remain, such as choice of drug(s), optimal duration of therapy and patient selection criteria......ABSTRACT: Angiogenesis is an important component of cancer growth, invasion and metastasis. Therefore, inhibition of angiogenesis is an attractive strategy for treatment of cancer. We describe existing clinical trials of antiangiogenic agents and the challenges facing the clinical development...

  2. Exploring circulating micro-RNA in the neoadjuvant treatment of breast cancer.

    Science.gov (United States)

    Casey, Máire-Caitlín; Sweeney, Karl J; Brown, James Andrew Lawrence; Kerin, Michael J

    2016-07-01

    Breast cancer is the most frequently diagnosed malignancy amongst females worldwide. In recent years the management of this disease has transformed considerably, including the administration of chemotherapy in the neoadjuvant setting. Aside from increasing rates of breast conserving surgery and enabling surgery via tumour burden reduction, use of chemotherapy in the neoadjuvant setting allows monitoring of in vivo tumour response to chemotherapeutics. Currently, there is no effective means of identifying chemotherapeutic responders from non-responders. Whilst some patients achieve complete pathological response (pCR) to chemotherapy, a good prognostic index, a proportion of patients derive little or no benefit, being exposed to the deleterious effects of systemic treatment without any knowledge of whether they will receive benefit. The identification of predictive and prognostic biomarkers could confer multiple benefits in this setting, specifically the individualization of breast cancer management and more effective administration of chemotherapeutics. In addition, biomarkers could potentially expedite the identification of novel chemotherapeutic agents or increase their efficacy. Micro-RNAs (miRNAs) are small non-coding RNA molecules. With their tissue-specific expression, correlation with clinicopathological prognostic indices and known dysregulation in breast cancer, miRNAs have quickly become an important avenue in the search for novel breast cancer biomarkers. We provide a brief history of breast cancer chemotherapeutics and explore the emerging field of circulating (blood-borne) miRNAs as breast cancer biomarkers for the neoadjuvant treatment of breast cancer. Established molecular markers of breast cancer are outlined, while the potential role of circulating miRNAs as chemotherapeutic response predictors, prognosticators or potential therapeutic targets is discussed. © 2016 The Authors International Journal of Cancer published by John Wiley & Sons Ltd on

  3. Rad51 supports triple negative breast cancer metastasis

    Science.gov (United States)

    Wiegmans, Adrian P; Al-Ejeh, Fares; Chee, Nicole; Yap, Pei-Yi; Gorski, Julia J; Silva, Leonard Da; Bolderson, Emma; Chenevix-Trench, Georgia; Anderson, Robin; Simpson, Peter T; Lakhani, Sunil R; Khanna, Kum Kum

    2014-01-01

    In contrast to extensive studies on familial breast cancer, it is currently unclear whether defects in DNA double strand break (DSB) repair genes play a role in sporadic breast cancer development and progression. We performed analysis of immunohistochemistry in an independent cohort of 235 were sporadic breast tumours. This analysis suggested that RAD51 expression is increased during breast cancer progression and metastasis and an oncogenic role for RAD51 when deregulated. Subsequent knockdown of RAD51 repressed cancer cell migration in vitro and reduced primary tumor growth in a syngeneic mouse model in vivo. Loss of RAD51 also inhibited associated metastasis not only in syngeneic mice but human xenografts and changed the metastatic gene expression profile of cancer cells, consistent with inhibition of distant metastasis. This demonstrates for the first time a new function of RAD51 that may underlie the proclivity of patients with RAD51 overexpression to develop distant metastasis. RAD51 is a potential biomarker and attractive drug target for metastatic triple negative breast cancer, with the capability to extend the survival of patients, which is less than 6 months. PMID:24811120

  4. Nanotechnology for breast cancer therapy.

    Science.gov (United States)

    Tanaka, Takemi; Decuzzi, Paolo; Cristofanilli, Massimo; Sakamoto, Jason H; Tasciotti, Ennio; Robertson, Fredika M; Ferrari, Mauro

    2009-02-01

    Breast cancer is the field of medicine with the greatest presence of nanotechnological therapeutic agents in the clinic. A pegylated form of liposomally encapsulated doxorubicin is routinely used for treatment against metastatic cancer, and albumin nanoparticulate chaperones of paclitaxel were approved for locally recurrent and metastatic disease in 2005. These drugs have yielded substantial clinical benefit, and are steadily gathering greater beneficial impact. Clinical trials currently employing these drugs in combination with chemo and biological therapeutics exceed 150 worldwide. Despite these advancements, breast cancer morbidity and mortality is unacceptably high. Nanotechnology offers potential solutions to the historical challenge that has rendered breast cancer so difficult to contain and eradicate: the extreme biological diversity of the disease presentation in the patient population and in the evolutionary changes of any individual disease, the multiple pathways that drive disease progression, the onset of 'resistance' to established therapeutic cocktails, and the gravity of the side effects to treatment, which result from generally very poor distribution of the injected therapeutic agents in the body. A fundamental requirement for success in the development of new therapeutic strategies is that breast cancer specialists-in the clinic, the pharmaceutical and the basic biological laboratory-and nanotechnologists-engineers, physicists, chemists and mathematicians-optimize their ability to work in close collaboration. This further requires a mutual openness across cultural and language barriers, academic reward systems, and many other 'environmental' divides. This paper is respectfully submitted to the community to help foster the mutual interactions of the breast cancer world with micro- and nano-technology, and in particular to encourage the latter community to direct ever increasing attention to breast cancer, where an extraordinary beneficial impact may

  5. Breast Cancer in Systemic Lupus Erythematosus

    DEFF Research Database (Denmark)

    Tessier Cloutier, B; Clarke, A E; Ramsey-Goldman, R

    2013-01-01

    Evidence points to a decreased breast cancer risk in systemic lupus erythematosus (SLE). We analyzed data from a large multisite SLE cohort, linked to cancer registries.......Evidence points to a decreased breast cancer risk in systemic lupus erythematosus (SLE). We analyzed data from a large multisite SLE cohort, linked to cancer registries....

  6. Triple-negative breast cancer

    OpenAIRE

    Chacón, Reinaldo D; Costanzo, María V

    2010-01-01

    Perou's molecular classification defines tumors that neither express hormone receptors nor overexpress HER2 as triple-negative (TN) tumors. These tumors account for approximately 15% of breast cancers. The so-called basaloid tumors are not always synonymous with TN tumors; they differ in the fact that they express different molecular markers, have a higher histologic grade, and have a worse prognosis. Clinically they occur in younger women as interval cancer, and the risk of recurrence is hig...

  7. Integrated Immunotherapy for Breast Cancer

    Science.gov (United States)

    2016-09-01

    or doxorubicin alone or in combination are shown. (C) Balb/c mice were challenged with 4T1.2 cells orthotopically in the mammary gland and received... mammary gland and received 6 oral daily doses of Ivermectin (5 mg/kg) alone or in combination with doxorubicin at 5 mg/kg. Comparisons between...Tumor stroma and regulation of cancer development. Annual review of pathology 1, 119 (2006). 11. M. M. Shao et al., A subset of breast cancer

  8. Breast Cancer Vaccines: New Insights

    OpenAIRE

    Benedetti, Rosaria; Dell’Aversana, Carmela; Giorgio, Cristina; Astorri, Roberta; Altucci, Lucia

    2017-01-01

    Breast cancer (BC) is a persistent global challenge for its high frequency in women (although it seldom occurs in men), due to the large diffusion of risk factors and gene mutations, and for its peculiar biology and microenvironment. To date, BC can benefit from different therapeutic strategies involving surgery, ablation, chemotherapy, radiotherapy, and more specific approaches such as hormone therapy and the administration of various substances impairing cancer growth, aggressivity, and rec...

  9. New serum biomarkers for prostate cancer diagnosis

    Science.gov (United States)

    Chadha, Kailash C.; Miller, Austin; Nair, Bindukumar B.; Schwartz, Stanley A.; Trump, Donald L.; Underwood, Willie

    2014-01-01

    Background Prostate-specific antigen (PSA) is currently used as a biomarker for diagnosis and management of prostate cancer (CaP). However, PSA typically lacks the sensitivity and specificity desired of a diagnostic marker. Objective The goal of this study was to identify an additional biomarker or a panel of biomarkers that is more sensitive and specific than PSA in differentiating benign versus malignant prostate disease and/or localized CaP versus metastatic CaP. Methods Concurrent measurements of circulating interleukin-8 (IL-8), Tumor necrosis factor-α (TNF-α) and soluble tumor necrosis factor-α receptors 1 (sTNFR1) were obtained from four groups of men: (1) Controls (2) with elevated prostate-specific antigen with a negative prostate biopsy (elPSA_negBx) (3) with clinically localized CaP and (4) with castration resistant prostate cancer. Results TNF-α Area under the receiver operating characteristic curve (AUC = 0.93) and sTNFR1 (AUC = 0.97) were strong predictors of elPSA_negBx (vs. CaP). The best predictor of elPSA_negBx vs CaP was sTNFR1 and IL-8 combined (AUC = 0.997). The strongest single predictors of localized versus metastatic CaP were TNF-α (AUC = 0.992) and PSA (AUC = 0.963) levels. Conclusions The specificity and sensitivity of a PSA-based CaP diagnosis can be significantly enhanced by concurrent serum measurements of IL-8, TNF-α and sTNFR1. In view of the concerns about the ability of PSA to distinguish clinically relevant CaP from indolent disease, assessment of these biomarkers in the larger cohort is warranted. PMID:25593898

  10. Difference in fatty acids composition of breast adipose tissue in women with breast cancer and benign breast disease.

    Science.gov (United States)

    Conceição, Lisiane Lopes da; Dias, Mariana De Moura; Pessoa, Milene Cristine; Pena, Geórgia Das Graças; Mendes, Maria Carolina Santos; Neves, Cristiane Vilas Boas; Hermsdorff, Helen Hermana Miranda; Freitas, Renata Nascimento; Peluzio, Maria do Carmo Gouveia

    2016-11-29

    Breast cancer is the second most common cancer in the world, and the most frequent cancer among women. Moreover, there are factors that influence the risk for breast cancer including the age, genetic and endocrine factors, and lifestyle. To evaluate the consumption of fatty acids; compare the fatty acids composition in the breast adipose tissue of women with breast cancer and benign breast disease as well as potential risk factors; and describe the genotypic frequency of the Pro12Ala PPARγ polymorphism. A hospital-based case-control study was conducted including incident cases (n= 38 breast cancer; n= 75 benign breast disease; n= 166 control). Lifestyle features, socioeconomic issues, dietary intake, anthropometry, and blood and tissue data were assessed. No differences were observed for fatty acids intake. Interestingly, lauric acid (p = 0.001), myristic acid (p = 0.036), stearic acid (p = 0.031), and total saturated fatty acids (SFAs) (p = 0.048) had lower concentrations in BC than in BBD women, while palmitoleic acid (p = 0.022), erucic acid (p = 0.002), total monounsaturated fatty acids (MUFAs) (p = 0.039) and oleic acid/stearic acid ratio (p = 0.015) increased. There was no significant association between PPARγ polymorphism and studied groups (p = 0.977). The age at first full pregnancy (p = 0.004) was significantly associated with the development BC, whereas BMI (p = 0.005); percentage of body fat (p = 0.024); physical activity (p = 0.036); and age at menarche (p = 0.008), at first full pregnancy (p breast adipose tissue, a biomarker of long-term dietary intake, particularly for SFAs, MUFA and 18: 1 n-9/18: 00 ratio. Our findings also show that are differences in the factors related to the development of BC and BBC.

  11. Imaging features of breast cancers on digital breast tomosynthesis according to molecular subtype: association with breast cancer detection.

    Science.gov (United States)

    Lee, Su Hyun; Chang, Jung Min; Shin, Sung Ui; Chu, A Jung; Yi, Ann; Cho, Nariya; Moon, Woo Kyung

    2017-12-01

    To evaluate imaging features of breast cancers on digital breast tomosynthesis (DBT) according to molecular subtype and to determine whether the molecular subtype affects breast cancer detection on DBT. This was an institutional review board--approved study with a waiver of informed consent. DBT findings of 288 invasive breast cancers were reviewed according to Breast Imaging Reporting and Data System lexicon. Detectability of breast cancer was quantified by the number of readers (0-3) who correctly detected the cancer in an independent blinded review. DBT features and the cancer detectability score according to molecular subtype were compared using Fisher's exact test and analysis of variance. Of 288 invasive cancers, 194 were hormone receptor (HR)-positive, 48 were human epidermal growth factor receptor 2 (HER2) positive and 46 were triple negative breast cancers. The most common DBT findings were irregular spiculated masses for HR-positive cancer, fine pleomorphic or linear branching calcifications for HER2 positive cancer and irregular masses with circumscribed margins for triple negative breast cancers (p Cancer detectability on DBT was not significantly different according to molecular subtype (p = 0.213) but rather affected by tumour size, breast density and presence of mass or calcifications. Breast cancers showed different imaging features according to molecular subtype; however, it did not affect the cancer detectability on DBT. Advances in knowledge: DBT showed characteristic imaging features of breast cancers according to molecular subtype. However, cancer detectability on DBT was not affected by molecular subtype of breast cancers.

  12. Risk of primary non-breast cancer after female breast cancer by age at diagnosis

    DEFF Research Database (Denmark)

    Mellemkjær, Lene; Christensen, Jane; Frederiksen, Kirsten Skovsgaard

    2011-01-01

    Women diagnosed with breast cancer at young age have been shown to be at higher risk of developing a new primary cancer than women diagnosed at older ages, but little is known about whether adjustment for calendar year of breast cancer diagnosis, length of follow-up, and/or breast cancer treatment...

  13. What You Need to Know about Breast Cancer

    Science.gov (United States)

    ... Publications Reports What You Need To Know About™ Breast Cancer This booklet is about breast cancer. Learning about your cancer can help you take ... This booklet covers: Basics about breast anatomy and breast cancer Treatments for breast cancer, including taking part in ...

  14. System delays in breast cancer

    African Journals Online (AJOL)

    In South Africa (SA), breast cancer is the 4th most common cause of death from all malignancies.[1] In SA, we notice a discrepancy in incidence rates between various ethnic/race groups. African women have rates similar to those in other developing countries. Caucasian women have rates that are comparable with ...

  15. Breast Cancer Startup Challenge winners

    Science.gov (United States)

    Ten winners of a world-wide competition to bring emerging breast cancer research technologies to market faster were announced today by the Avon Foundation for Women, in partnership with NCI and the Center for Advancing Innovation (CAI). Avon is providing

  16. Estrogen Metabolism and Breast Cancer

    African Journals Online (AJOL)

    pathway mediated by the generation and redox Cycling of reactive oxygen species through the metabolic effects of estrogen .... therapy. Several studies including the European. Organization for Research and Treatment of. Cancer ÇEORTC) trial,19 the ATAC (Arimidex, tamoxifen, alone or in combination) adjuvant breast.

  17. Genetic determinants of breast cancer

    NARCIS (Netherlands)

    A.M. Gonzalez-Zuloeta Ladd (Angela)

    2007-01-01

    textabstractBreast cancer is the most common malignancy in women in the Western world and it is estimated that women who survive to the age of 85 years will have a 1 in 9 lifetime probability of developing this type of neoplasia (1, 2). The degree of risk is not spread homogeneously across the

  18. Precision medicine and personalized breast cancer: combination pertuzumab therapy

    Directory of Open Access Journals (Sweden)

    Reynolds K

    2014-03-01

    Full Text Available Kerry Reynolds, Sasmit Sarangi, Aditya Bardia, Don S Dizon Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA Abstract: Trastuzumab (Herceptin, a monoclonal antibody directed against the human epidermal growth-factor receptor 2 (HER2, is the poster child for antibody-based targeted therapy in breast cancer. Pertuzumab, another humanized monoclonal antibody, binds to a different domain of HER2 and prevents the formation of HER2:HER3 dimers, which is the most potent heterodimer in the HER family. The combination of trastuzumab and pertuzumab has synergistic activity, and is associated with improved clinical outcomes. The US Food and Drug Administration (FDA approved pertuzumab in combination with trastuzumab-based chemotherapy originally as first-line therapy for metastatic HER2-positive breast cancer in 2012, and more recently as neoadjuvant therapy for localized disease in 2013. Pertuzumab is the first neoadjuvant drug to receive accelerated approval by the FDA based on pathological complete response as the primary end point. In this article, we review the mechanism of action, pharmacokinetics, clinical efficacy, safety, and current role of pertuzumab in the management of breast cancer, as well as ongoing clinical trials and future directions regarding the utility of pertuzumab as a personalized therapeutic option for HER2-positive breast cancer. In the coming years, we anticipate increased utilization of neoadjuvant trials for drug development, biomarker discovery, and validation, and envision conduct of personalized breast cancer clinics in which therapies will be routinely selected based on genetic alterations in the tumor. Regardless of the targeted therapy combinations employed based on tumor genomic profile, trastuzumab and pertuzumab will likely continue to form the backbone of the personalized regimen for HER2-positive breast cancer. Keywords: pertuzumab, HER2 breast cancer, personalized therapy

  19. Progesterone Receptor Scaffolding Function in Breast Cancer

    Science.gov (United States)

    2012-10-01

    response. PR are expressed in multiple human tissues including the uterus, mammary gland , brain, pancreas, thymus , bone, ovary, testes, and in the...ABSTRACT Progesterone receptors (PR) are critical mediators of mammary gland development and contribute to breast cancer progression. Progestin...receptors (PR) are critical for massive breast epithelial cell expansion during mammary gland development and contribute to breast cancer progression

  20. Magnetic resonance imaging of invasive breast cancer

    African Journals Online (AJOL)

    G5

    graphic findings, and screening for breast cancer in younger women with familial breast cancer. Interpretation of MR images requires a meticulous imaging technique including the use of contrast enhancement and fat suppression MR sequences using a good breast coil. Introduction. The role of MR imaging in the diagno-.