Promoting breast screening in Glasgow.

PubMed

Cohen, L; Dobson, H; McGuire, F

2000-03-01

To establish whether there is a role for advertising in the promotion of the Breast Screening Programme and what the role of advertising might be. Four hundred and sixty questionnaires were completed by women attending their breast screening appointment. Quantitative and qualitative data were collected from the static unit at Calder Street and the mobile unit in Govan. The advertising (budget 30,000 Pounds) campaign ran over an eight week period in the Govan, Paisley Road West and Cardonald areas of Glasgow. Media used included press advertising, The Glasgow Underground, adshells, bus advertising (interiors) and poster distribution via local outlets. Forty-two per cent of the sample were aware of the campaign. Ninety-seven per cent liked the campaign images. Eighty eight per cent felt that breast screening should be advertised more. Screening uptake increased in the areas covered by the advertising campaign. Govan -58%-71% and Ibrox (Paisley Road West and Cardonald) -59%-61%. Women were very supportive of the role of advertising for the Breast Screening Programme. In particular they found the campaign images and messages reassuring, supportive and credible. Their views suggest that the role of advertising should be: To raise awareness of the service To make women more conscious of the benefits of screening To change public perceptions of the screening process However, it is recognised that a fully integrated approach is required for the promotion of the service to account for the improvement in uptake, as advertising cannot be expected to work in isolation.

Effect of hypoxia on tissue factor pathway inhibitor expression in breast cancer.

PubMed

Cui, X Y; Tinholt, M; Stavik, B; Dahm, A E A; Kanse, S; Jin, Y; Seidl, S; Sahlberg, K K; Iversen, N; Skretting, G; Sandset, P M

2016-02-01

ESSENTIALS: A hypoxic microenvironment is a common feature of tumors that may influence activation of coagulation. MCF-7 and SK-BR-3 breast cancer cells and breast cancer tissue samples were used. The results showed transcriptional repression of tissue factor pathway inhibitor expression in hypoxia. Hypoxia-inducible factor 1α may be a target for the therapy of cancer-related coagulation and thrombosis. Activation of coagulation is a common finding in patients with cancer, and is associated with an increased risk of venous thrombosis. As a hypoxic microenvironment is a common feature of solid tumors, we investigated the role of hypoxia in the regulation of tissue factor (TF) pathway inhibitor (TFPI) expression in breast cancer. To explore the transcriptional regulation of TFPI by hypoxia-inducible factor (HIF)-1α in breast cancer cells and their correlation in breast cancer tissues. MCF-7 and SK-BR-3 breast cancer cells were cultured in 1% oxygen or treated with cobalt chloride (CoCl2 ) to mimic hypoxia. Time-dependent and dose-dependent downregulation of TFPI mRNA (quantitative RT-PCR) and of free TFPI protein (ELISA) were observed in hypoxia. Western blotting showed parallel increases in the levels of HIF-1α protein and TF. HIF-1α inhibitor abolished or attenuated the hypoxia-induced downregulation of TFPI. Luciferase reporter assay showed that both hypoxia and HIF-1α overexpression caused strong repression of TFPI promoter activity. Subsequent chromatin immunoprecipitation and mutagenesis analysis demonstrated a functional hypoxia response element within the TFPI promoter, located at -1065 to -1060 relative to the transcriptional start point. In breast cancer tissue samples, gene expression analyses showed a positive correlation between the mRNA expression of TFPI and that of HIF-1α. This study demonstrates that HIF-1α is involved in the transcriptional regulation of the TFPI gene, and suggests that a hypoxic microenvironment inside a breast tumor may

Imaging Management of Breast Density, a Controversial Risk Factor for Breast Cancer.

PubMed

Falcon, Shannon; Williams, Angela; Weinfurtner, Jared; Drukteinis, Jennifer S

2017-04-01

Breast density is well recognized as an independent risk factor for the development of breast cancer. However, the magnitude of risk is controversial. As the public becomes increasingly aware of breast density as a risk factor, legislation and notification laws in relation to breast density have become common throughout the United States. Awareness of breast density as a risk factor for breast cancer presents new challenges for the clinician in the approach to the management and screening of women with dense breasts. The evidence and controversy surrounding breast density as a risk factor for the development of breast cancer are discussed. Common supplemental screening modalities for breast cancer are also discussed, including tomosynthesis, ultrasonography, and magnetic resonance imaging. A management strategy for screening women with dense breasts is also presented. The American College of Radiology recognizes breast density as a controversial risk factor for breast cancer, whereas the American Congress of Obstetricians and Gynecologists recognizes breast density as a modest risk factor. Neither organization recommends the routine use of supplemental screening in women with dense breasts without considering additional patient-related risk factors. Breast density is a poorly understood and controversial risk factor for the development of breast cancer. Mammography is a screening modality proven to reduce breast cancer-related mortality rates and is the single most appropriate tool for population-based screening. Use of supplemental screening modalities should be tailored to individual risk assessment.

Coagulation factor VII is regulated by androgen receptor in breast cancer.

PubMed

Naderi, Ali

2015-02-01

Androgen receptor (AR) is widely expressed in breast cancer; however, there is limited information on the key molecular functions and gene targets of AR in this disease. In this study, gene expression data from a cohort of 52 breast cancer cell lines was analyzed to identify a network of AR co-expressed genes. A total of 300 genes, which were significantly enriched for cell cycle and metabolic functions, showed absolute correlation coefficients (|CC|) of more than 0.5 with AR expression across the dataset. In this network, a subset of 35 "AR-signature" genes were highly co-expressed with AR (|CC|>0.6) that included transcriptional regulators PATZ1, NFATC4, and SPDEF. Furthermore, gene encoding coagulation factor VII (F7) demonstrated the closest expression pattern with AR (CC=0.716) in the dataset and factor VII protein expression was significantly associated to that of AR in a cohort of 209 breast tumors. Moreover, functional studies demonstrated that AR activation results in the induction of factor VII expression at both transcript and protein levels and AR directly binds to a proximal region of F7 promoter in breast cancer cells. Importantly, AR activation in breast cancer cells induced endogenous factor VII activity to convert factor X to Xa in conjunction with tissue factor. In summary, F7 is a novel AR target gene and AR activation regulates the ectopic expression and activity of factor VII in breast cancer cells. These findings have functional implications in the pathobiology of thromboembolic events and regulation of factor VII/tissue factor signaling in breast cancer. Copyright © 2014 Elsevier Inc. All rights reserved.

Evaluation of breast cancer knowledge among health promoters in Mexico before and after focused training.

PubMed

Keating, Nancy L; Kouri, Elena M; Ornelas, Héctor Arreola; Méndez, Oscar; Valladares, Laura Magaña; Knaul, Felicia Marie

2014-10-01

Breast cancer is a leading cause of morbidity and mortality in Mexico. We assessed the effectiveness of a train-the-trainer program in two Mexican states in improving knowledge among professional and nonprofessional community health workers. We worked with local organizations to develop and implement a train-the-trainer program to improve breast cancer knowledge among community health workers, including professional health promoters (PHPs) who were trained and then trained nonprofessional community health promoters (CHPs). We surveyed participants before and after training that included in-person and online classes and again approximately 3 months later. We used paired t tests and chi-square tests to compare survey responses at the different times. We also used logistic regression to assess whether promoter characteristics were associated with greater improvements in breast cancer knowledge after training. Overall, 169 PHPs (mean age, 36 years) completed training and provided a 10-hour training course to 2,651 CHPs, who also completed the pre- and post-training survey. For both PHPs and CHPs, post-training surveys demonstrated increases in an understanding of breast cancer as a problem; an understanding of screening, treatment, and insurance coverage issues; and knowledge of breast cancer risk factors, symptoms, and what constitutes a family history of breast cancer (all p < .05). These improvements were maintained 3 to 6 months after training. Train-the-trainer programs hold promise for leveraging community health workers, who far outnumber other health professionals in many low- and middle-income countries, to engage in health promotion activities for cancer and other noncommunicable diseases. ©AlphaMed Press.

Using quality improvement to promote breast-feeding in a local health department.

PubMed

Wright, Sarah S; Lea, C Suzanne; Holloman, Roxanne; Cornett, Amanda; Harrison, Lisa Macon; Randolph, Greg D

2012-01-01

In 2008, breast-feeding initiation and continuation rates in Beaufort County, North Carolina, were lower than statewide rates. A quality improvement (QI) project was initiated to increase breast-feeding rates by enhancing the overall environment that supports breast-feeding at the Beaufort County Health Department. This case study describes one of the first QI initiatives implemented through the North Carolina Center for Public Health Quality QI training program, conducted in 2009. The aim of this project was to improve the health and wellness of mothers and infants in Beaufort County by promoting breast-feeding among Beaufort County Health Department Women, Infants and Children (WIC) clients. Using QI tools, 4 new approaches to breast-feeding promotion were tested and implemented: creating a nurturing location to breast-feed while at the health department, actively telephoning new mothers to provide breast-feeding support, incentivizing adoption of educational messages by providing a breast-feeding tote bag, and promoting new WIC food packages. These enhancements involved staff in QI planning and implementation and correlated with improved breast-feeding initiation for WIC clients during the year following project completion.

Epigenetic Changes of the ESR1 Gene in Breast Tissue of Healthy Women: A Missing Link with Breast Cancer Risk Factors?

PubMed

Daraei, Abdolreza; Izadi, Pantea; Khorasani, Ghasemali; Nafissi, Nahid; Naghizadeh, Mohammad Mehdi; Younosi, Nasim; Meysamie, Alipasha; Mansoori, Yaser; Bastami, Milad; Tavakkoly-Bazzaz, Javad

2017-08-01

Reproductive history and obesity are among the well-recognized risk factors in the development of breast cancer, which are partially mediated by the increased exposure of breast tissues to estrogens. However, only a few studies have investigated the link between these risk factors and the pattern of methylation signatures in the breast tissue of healthy women. The role of the estrogen receptor 1 (ESR1) gene hypermethylation is reportedly important in the development of breast cancer. Thus, it is speculated that such ESR1 epigenetic changes may be influenced or shaped by obesity and reproductive history-related factors before and during breast carcinogenesis. Breast samples were collected from 120 cancer-free women who had undergone cosmetic mammoplasty. DNA was extracted from the breast tissues and, then, the methylation levels at the promoter and exon 1 regions of the ESR1 gene CpG island were determined by using the methylated DNA immunoprecipitation-quantitative PCR assay. The methylation level of the ESR1 promoter observed in women with a body mass index (BMI) ≥30 kg/m 2 (p ≤ 0.001) was higher than in the subgroups of women of BMI <25 kg/m 2 (p < 0.001) and BMI 25-29 kg/m 2 (p < 0.001) and was also higher in postmenopausal women compared with that in premenopausal women (p = 0.046). Pearson correlation coefficient analyses also showed that the high methylation of the ESR1 promoter was correlated with increasing age (r = -0.246, p = 0.007) and BMI (r = -0.331, p ≤ 0.001). Finally, linear multivariate regression revealed a significant association between high methylation rates in the ESR1 gene promoter and increased BMI (β = -0.285, 95% CI = -0.457 to -0.113, p = 0.001). Furthermore, a higher methylation level at the ESR1 gene exon 1 was found in the BMI ≥ 30 kg/m 2 subgroup compared to the BMI 25-29 kg/m 2 subgroup (p = 0.023). These findings provide new hints about the relationship between

ABL kinases promote breast cancer osteolytic metastasis by modulating tumor-bone interactions through TAZ and STAT5 signaling

PubMed Central

Wang, Jun; Rouse, Clay; Jasper, Jeff S.; Pendergast, Ann Marie

2016-01-01

Bone metastases occur in up to 70% of advanced breast cancer. For most patients with breast cancer, bone metastases are predominantly osteolytic. Interactions between tumor cells and stromal cells in the bone microenvironment drive osteolytic bone metastasis, a process that requires the activation of osteoclasts, cells that break down bone. Here, we report that ABL kinases promoted metastasis of breast cancer cells to bone by regulating the crosstalk between tumor and the bone microenvironment. ABL kinases protected tumor cells from apoptosis induced by TRAIL (TNF-related apoptosis-inducing ligand), activated the transcription factor STAT5, and promoted osteolysis through the STAT5-dependent expression of genes encoding the osteoclast activating factors interleukin 6 (IL6) and matrix metalloproteinase-1 (MMP1). Furthermore, ABL kinases increased the abundance of the Hippo pathway mediator TAZ and the expression of TAZ-dependent target genes that promote bone metastasis. Knockdown of ABL kinases or treatment with ABL-specific allosteric inhibitor impaired osteolytic metastasis of breast cancer cells in mice. These findings revealed a role for ABL kinases in regulating tumor-bone interactions and provide a rationale for targeting both tumor and the bone microenvironment with ABL-specific inhibitors. PMID:26838548

[Effects of a breast feeding promotion program for working women].

PubMed

Yoon, Ji-Won; Park, Young-Joo

2008-12-01

The purpose of this study was to measure the effects of a breast feeding promotion program for working women on breast feeding continuation, mother-infant attachment, and maternal sensitivity. The design of this study is nonequivalent control group design with repeated measures. There were significant differences in breast feeding continuation between two groups at each time point except 2 days and 1 week after delivery. The scores of mother-infant attachment and maternal sensitivity of experimental group were higher than those of the control group, but there were no significant differences between two groups. Although some modifications in contents and administration will be required to increase the effectiveness of the program, breast feeding promotion program for working women can be an effective nursing intervention which can facilitate breast feeding continuation and mother-infant relationships.

G-protein-coupled receptor 81 promotes a malignant phenotype in breast cancer through angiogenic factor secretion.

PubMed

Lee, Yu Jin; Shin, Kyeong Jin; Park, Soo-Ah; Park, Kyeong Su; Park, Seorim; Heo, Kyun; Seo, Young-Kyo; Noh, Dong-Young; Ryu, Sung Ho; Suh, Pann-Ghill

2016-10-25

G-protein-coupled receptor 81 (GPR81) functions as a receptor for lactate and plays an important role in the regulation of anti-lipolytic effects in adipocytes. However, to data, a role for GPR81 in the tumor microenvironment has not been clearly defined. Here, GPR81 expression in breast cancer patients and several breast cancer cell lines was significantly increased compared with normal mammary tissues and cells. GPR81 knockdown resulted in impaired breast cancer growth and led to apoptosis both in vitro and in vivo. Furthermore, the inhibition of GPR81 signaling suppressed angiogenesis through a phosphoinositide 3-OH kinase (PI3K)/Akt-cAMP response element binding protein (CREB) pathway, which led to decreased production of the pro-angiogenic mediator amphiregulin (AREG). Overall, these findings identify GPR81 as a tumor-promoting receptor in breast cancer progression and suggest a novel mechanism that regulates GPR81-dependent activation of the PI3K/Akt signaling axis in tumor microenvironment.

Breast-feeding Continuation in South-Eastern of Iran: the Associated Factors

PubMed Central

Roostaee, Fatemeh; Tabatabaei, Seyed Mehdi; Zaboli, Maryam; Keykhaie, Razieh; Sharifi-Rad, Javad; Shahrak, Paridokht; Soroush, Fatemeh

2015-01-01

Background: Breast-feeding not only promotes health in an infancy period, but also leads to human vigor and safety at varied life periods viz. adolescence, youth, middle-age, or even adulthood. Aim: The present study was aimed to determine the factors affecting the breast-feeding continuation effectively for a selected region of Iran. Methods: This cross-sectional study was performed on 523 women having less than two year old babies from the selected counties covered by the Zahedan University of Medical Sciences (Khash, Saravan, Sarbaz, Chabahar, Zahedan, Nikshahr, Iranshahr, and Konark) using the stratified sampling method. The Data was completed for the target group by using the check-list which included 3 parts: demographic data, case history of pregnancy, childbirth and mother’s statue, and previous records of the newborn up to two years. The obtained data were fed into SPSS software, and all parametric and non-parametric statistical methods were used to analyze the data, especially appropriate to the data type. Results: The results showed that the most important factors associated with breast-feeding discontinuation were infant’s illness (only up to six months), mother’s consciousness, parental support, practical breastfeeding training to the mother, mother’s educational level, child’s gender, place of birth, pregnancies’ interval, mother’s ethnicity and residence and the statue of taking (using) narcotics. The data also indicated that on maternal reasons the main factor which impelled most of the mothers to discontinue their breast-feeding up to six months or even before two years was milk shortage in mother’s breasts. Moreover, the main child- related factor that compelled most of the mothers for non-continuance of their breast-feeding up to six months or even before two years was child’s crying and discomfort. Conclusions: It can be safely concluded that promotion of parental education, neglecting child’s gender as far as cultural

Pro-oncogene Pokemon promotes breast cancer progression by upregulating survivin expression.

PubMed

Zu, Xuyu; Ma, Jun; Liu, Hongxia; Liu, Feng; Tan, Chunyan; Yu, Lingling; Wang, Jue; Xie, Zhenhua; Cao, Deliang; Jiang, Yuyang

2011-03-10

Pokemon is an oncogenic transcription factor involved in cell growth, differentiation and oncogenesis, but little is known about its role in human breast cancer. In this study, we aimed to reveal the role of Pokemon in breast cancer progression and patient survival and to understand its underlying mechanisms. Tissue microarray analysis of breast cancer tissues from patients with complete clinicopathological data and more than 20 years of follow-up were used to evaluate Pokemon expression and its correlation with the progression and prognosis of the disease. DNA microarray analysis of MCF-7 cells that overexpress Pokemon was used to identify Pokemon target genes. Chromatin immunoprecipitation (ChIP) and site-directed mutagenesis were utilized to determine how Pokemon regulates survivin expression, a target gene. Pokemon was found to be overexpressed in 158 (86.8%) of 182 breast cancer tissues, and its expression was correlated with tumor size (P = 0.0148) and lymph node metastasis (P = 0.0014). Pokemon expression led to worse overall (n = 175, P = 0.01) and disease-related (n = 79, P = 0.0134) patient survival. DNA microarray analyses revealed that in MCF-7 breast cancer cells, Pokemon regulates the expression of at least 121 genes involved in several signaling and metabolic pathways, including anti-apoptotic survivin. In clinical specimens, Pokemon and survivin expression were highly correlated (n = 49, r = 0.6799, P < 0.0001). ChIP and site-directed mutagenesis indicated that Pokemon induces survivin expression by binding to the GT boxes in its promoter. Pokemon promotes breast cancer progression by upregulating survivin expression and thus may be a potential target for the treatment of this malignancy.

Pro-oncogene Pokemon promotes breast cancer progression by upregulating survivin expression

PubMed Central

2011-01-01

Introduction Pokemon is an oncogenic transcription factor involved in cell growth, differentiation and oncogenesis, but little is known about its role in human breast cancer. In this study, we aimed to reveal the role of Pokemon in breast cancer progression and patient survival and to understand its underlying mechanisms. Methods Tissue microarray analysis of breast cancer tissues from patients with complete clinicopathological data and more than 20 years of follow-up were used to evaluate Pokemon expression and its correlation with the progression and prognosis of the disease. DNA microarray analysis of MCF-7 cells that overexpress Pokemon was used to identify Pokemon target genes. Chromatin immunoprecipitation (ChIP) and site-directed mutagenesis were utilized to determine how Pokemon regulates survivin expression, a target gene. Results Pokemon was found to be overexpressed in 158 (86.8%) of 182 breast cancer tissues, and its expression was correlated with tumor size (P = 0.0148) and lymph node metastasis (P = 0.0014). Pokemon expression led to worse overall (n = 175, P = 0.01) and disease-related (n = 79, P = 0.0134) patient survival. DNA microarray analyses revealed that in MCF-7 breast cancer cells, Pokemon regulates the expression of at least 121 genes involved in several signaling and metabolic pathways, including anti-apoptotic survivin. In clinical specimens, Pokemon and survivin expression were highly correlated (n = 49, r = 0.6799, P < 0.0001). ChIP and site-directed mutagenesis indicated that Pokemon induces survivin expression by binding to the GT boxes in its promoter. Conclusions Pokemon promotes breast cancer progression by upregulating survivin expression and thus may be a potential target for the treatment of this malignancy. PMID:21392388

Prohibitin promotes androgen receptor activation in ER-positive breast cancer

PubMed Central

Liu, Pengying; Xu, Yumei; Zhang, Wenwen; Li, Yan; Tang, Lin; Chen, Weiwei; Xu, Jing; Sun, Qian; Guan, Xiaoxiang

2017-01-01

ABSTRACT Prohibitin (PHB) is an evolutionarily conserved protein with multiple functions in both normal and cancer cells. Androgen receptor (AR) was reported to act as a different role in the ER-positive and ER-negative breast cancer. However, little is known about the role of PHB and whether PHB could regulate AR expression in the ER-positive breast cancer. Here, we determined the expression and clinical outcomes of PHB in breast cancer samples using 121 breast cancer tissues and published databases, and investigated the role of PHB in breast cancer cell growth, apoptosis and cell cycle arrest in the ER-positive breast cancer cells. We obtained the expression of PHB is significantly low in breast cancer samples, and low PHB expression positively correlated with poor prognosis of breast cancer. We detected that PHB could inhibit breast cancer cell proliferation, change cell cycle distribution and promote cell apoptosis in the ER-positive breast cancer cells. Moreover, we found PHB could significantly increase AR expression in both mRNA and protein levels in the ER-positive breast cancer cells. Additionally, a significant positive correlation between PHB and AR expression was identified in the 121 breast cancer tissues. PHB and AR expression are associated with prognosis in the ER-positive breast cancer patients. Our results indicate that PHB promotes AR activation in ER-positive breast cancer, making PHB and AR potential molecular targets for ER-positive breast cancer therapy. PMID:28272969

Increased Eps15 homology domain 1 and RAB11FIP3 expression regulate breast cancer progression via promoting epithelial growth factor receptor recycling.

PubMed

Tong, Dandan; Liang, Ya-Nan; Stepanova, A A; Liu, Yu; Li, Xiaobo; Wang, Letian; Zhang, Fengmin; Vasilyeva, N V

2017-02-01

1 has a tumor suppressor function, and the combined marker of Eps15 homology domain 1/phosphorylation of epithelial growth factor receptor expression was identified as a better prognostic marker in breast cancer diagnosis. Furthermore, RAB11FIP3 combines with Eps15 homology domain 1 to promote the endocytosis recycling of phosphorylation of epithelial growth factor receptor.

[Promotion of breast feeding in paediatric outpatient settings].

PubMed

Böse-O'Reilly, S; Wermuth, I; Hellmann, J; Siebert, U; Lob-Corzilius, T

2008-03-01

With some data and examples it can be shown that the competence and the knowledge of paediatric doctor's assistants and paediatric nurses can and should be improved. The training courses to become a "prevention assistant" have been very positively accepted by doctor's assistants and paediatric nurses, and it seems an appropriate method to reach these aims. Prevention and especially promotion of breast feeding is possible in paediatric outpatient settings. The immediate contact between infants, parents, paediatric doctor's assistants, paediatric nurses, and doctors offers a unique opportunity to promote the health of children, mainly due to the high acceptance of regular check-ups. So why not introduce the promotion of breast feeding in paediatric outpatient settings with specially trained doctor's assistants and paediatric nurses?

Evaluation of Breast Cancer Knowledge Among Health Promoters in Mexico Before and After Focused Training

PubMed Central

Keating, Nancy L.; Kouri, Elena M.; Ornelas, Héctor Arreola; Méndez, Oscar; Valladares, Laura Magaña

2014-01-01

Objective. Breast cancer is a leading cause of morbidity and mortality in Mexico. We assessed the effectiveness of a train-the-trainer program in two Mexican states in improving knowledge among professional and nonprofessional community health workers. Materials and Methods. We worked with local organizations to develop and implement a train-the-trainer program to improve breast cancer knowledge among community health workers, including professional health promoters (PHPs) who were trained and then trained nonprofessional community health promoters (CHPs). We surveyed participants before and after training that included in-person and online classes and again approximately 3 months later. We used paired t tests and chi-square tests to compare survey responses at the different times. We also used logistic regression to assess whether promoter characteristics were associated with greater improvements in breast cancer knowledge after training. Results. Overall, 169 PHPs (mean age, 36 years) completed training and provided a 10-hour training course to 2,651 CHPs, who also completed the pre- and post-training survey. For both PHPs and CHPs, post-training surveys demonstrated increases in an understanding of breast cancer as a problem; an understanding of screening, treatment, and insurance coverage issues; and knowledge of breast cancer risk factors, symptoms, and what constitutes a family history of breast cancer (all p < .05). These improvements were maintained 3 to 6 months after training. Conclusion. Train-the-trainer programs hold promise for leveraging community health workers, who far outnumber other health professionals in many low- and middle-income countries, to engage in health promotion activities for cancer and other noncommunicable diseases. PMID:25232041

Fibroblast growth factor receptors in breast cancer.

PubMed

Wang, Shuwei; Ding, Zhongyang

2017-05-01

Fibroblast growth factor receptors are growth factor receptor tyrosine kinases, exerting their roles in embryogenesis, tissue homeostasis, and development of breast cancer. Recent genetic studies have identified some subtypes of fibroblast growth factor receptors as strong genetic loci associated with breast cancer. In this article, we review the recent epidemiological findings and experiment results of fibroblast growth factor receptors in breast cancer. First, we summarized the structure and physiological function of fibroblast growth factor receptors in humans. Then, we discussed the common genetic variations in fibroblast growth factor receptors that affect breast cancer risk. In addition, we also introduced the potential roles of each fibroblast growth factor receptors isoform in breast cancer. Finally, we explored the potential therapeutics targeting fibroblast growth factor receptors for breast cancer. Based on the biological mechanisms of fibroblast growth factor receptors leading to the pathogenesis in breast cancer, targeting fibroblast growth factor receptors may provide new opportunities for breast cancer therapeutic strategies.

CDKL2 promotes epithelial-mesenchymal transition and breast cancer progression

PubMed Central

Li, Linna; Liu, Chunping; Amato, Robert J.; Chang, Jeffrey T.; Du, Guangwei; Li, Wenliang

2014-01-01

The epithelial–mesenchymal transition (EMT) confers mesenchymal properties on epithelial cells and has been closely associated with the acquisition of aggressive traits by epithelial cancer cells. To identify novel regulators of EMT, we carried out cDNA screens that covered 500 human kinases. Subsequent characterization of candidate kinases led us to uncover cyclin-dependent kinase-like 2 (CDKL2) as a novel potent promoter for EMT and breast cancer progression. CDKL2-expressing human mammary gland epithelial cells displayed enhanced mesenchymal traits and stem cell-like phenotypes, which was acquired through activating a ZEB1/E-cadherin/β-catenin positive feedback loop and regulating CD44 mRNA alternative splicing to promote conversion of CD24high cells to CD44high cells. Furthermore, CDKL2 enhanced primary tumor formation and metastasis in a breast cancer xenograft model. Notably, CDKL2 is expressed significantly higher in mesenchymal human breast cancer cell lines than in epithelial lines, and its over-expression/amplification in human breast cancers is associated with shorter disease-free survival. Taken together, our study uncovered a major role for CDKL2 in promoting EMT and breast cancer progression. PMID:25333262

Web site development: applying aesthetics to promote breast health education and awareness.

PubMed

Thomas, Barbara; Goldsmith, Susan B; Forrest, Anne; Marshall, Renée

2002-01-01

This article describes the process of establishing a Web site as part of a collaborative project using visual art to promote breast health education. The need for a more "user-friendly" comprehensive breast health Web site that is aesthetically rewarding was identified after an analysis of current Web sites available through the World Wide Web. Two predetermined sets of criteria, accountability and aesthetics, were used to analyze these sites and to generate ideas for creating a breast health education Web site using visual art. Results of the analyses conducted are included as well as the factors to consider for incorporating into a Web site. The process specified is thorough and can be applied to establish a Web site that is aesthetically rewarding and informative for a variety of educational purposes.

Factors Affecting Preferences of Iranian Women for Breast Cancer Screening Based on Marketing Mix Components.

PubMed

Pourfarzi, Farhad; Fouladi, Nasrin; Amani, Firouz; Ahari, Saeid Sadegieh; Roshani, Zohre; Alimohammadi, Sara

2016-01-01

According to recent statistics, the breast cancer rate is growing fast in developing countries. In North West Iran, the incidence of breast cancer after esophageal and gastric cancers has the highest rate. Previous studies have also indicated that women in this region show reluctance to do breast cancer screening. There is a great need for change to promote breast cancer screening among women. Social marketing is a discipline that uses the systematic application of commercial marketing techniques to promote the adoption of behavior by the target audience. In the present qualitative study, thirty-two women with breast cancer were interviewed about their experiences of breast cancer screening. A semi-structured interview guide was designed to elicit information specific to the 4 P's in social marketing. Three main categories emerged from the analysis: price, service and promotion. Subcategories related to these main categories included factors effective in increasing and decreasing cost of screening, current and desirable features of screening services, and weakness of promotion. Screening programs should be designed to be of low cost, to meet patients' needs and should be provided in suitable places. Furthermore, it is essential that the cultural beliefs of society be improved through education. It seems necessary to design an executive protocol for breast cancer screening at different levels of primary health care to increase the women's willingness to undergo screening.

Omega-3 free fatty acids attenuate insulin-promoted breast cancer cell proliferation.

PubMed

Guo, Yang; Zhu, Sheng-Long; Wu, Yi-Kuan; He, Zhao; Chen, Yong-Quan

2017-06-01

High insulin levels in obese people are considered as a risk factor to induce breast carcinogenesis. And consumption of fish oils which mainly contain omega-3 fatty acids is associated with a reduced risk of breast cancer. However, whether omega-3 free fatty acids (FFAs) modulate insulin signaling pathway to prevent breast cancer is poorly understood. The current study tested the hypothesis that omega-3 FFAs attenuate insulin-induced breast cancer cell proliferation and regulate insulin signaling pathway. We show here that omega-3 FFAs attenuate MCF-7 cell proliferation and Akt and Erk1/2 phosphorylation levels stimulated by insulin. Knockdown Shp2 by siRNA resulted in significantly elevated omega-3 FFAs-activated Akt phosphorylation but failed to change insulin-stimulated Akt and Erk1/2 phosphorylation. And viable cell number was not affected by either downregulation of Shp2 expression or Erk1/2 inhibitor U0126 treatment. These observations indicated that omega-3 FFAs attenuate insulin-promoted breast cancer cell proliferation and insulin-activated Akt phosphorylation. Copyright © 2017 Elsevier Inc. All rights reserved.

FoxD3 deficiency promotes breast cancer progression by induction of epithelial–mesenchymal transition

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chu, Tian-Li; Zhao, Hong-Meng; Breast Surgery, Tianjin Medical University Cancer Institute and Hospital, Tianjin

2014-04-04

Highlights: • FOXD3 is down-regulated in breast cancer tissues. • FOXD3 inhibits breast cancer cell proliferation and invasion. • FoxD3 deficiency induces epithelial–mesenchymal transition. - Abstract: The transcription factor forkhead box D3 (FOXD3) plays an important role in the development of neural crest and gastric cancer cells. However, the function and mechanisms of FOXD3 in the breast tumorigenesis and progression is still limited. Here, we report that FOXD3 is a tumor suppressor of breast cancer tumorigenicity and aggressiveness. We found that FOXD3 is down-regulated in breast cancer tissues. Patients with low FOXD3 expression have a poor outcome. Depletion of FOXD3more » expression promotes breast cancer cell proliferation and invasion in vitro, whereas overexpression of FOXD3 inhibits breast cancer cell proliferation and invasion both in vitro and in vivo. In addition, depletion of FOXD3 is linked to epithelial–mesenchymal transition (EMT)-like phenotype. Our results indicate FOXD3 exhibits tumor suppressive activity and may be useful for breast therapy.« less

Carcinoma associated fibroblasts (CAFs) promote breast cancer motility by suppressing mammalian Diaphanous-related formin-2 (mDia2).

PubMed

Dvorak, Kaitlyn M; Pettee, Krista M; Rubinic-Minotti, Kaitlin; Su, Robin; Nestor-Kalinoski, Andrea; Eisenmann, Kathryn M

2018-01-01

The tumor microenvironment (TME) promotes tumor cell invasion and metastasis. An important step in the shift to a pro-cancerous microenvironment is the transformation of normal stromal fibroblasts to carcinoma-associated fibroblasts (CAFs). CAFs are present in a majority of solid tumors and can directly promote tumor cell motility via cytokine, chemokine and growth factor secretion into the TME. The exact effects that the TME has upon cytoskeletal regulation in motile tumor cells remain enigmatic. The conserved formin family of cytoskeleton regulating proteins plays an essential role in the assembly and/or bundling of unbranched actin filaments. Mammalian Diaphanous-related formin 2 (mDia2/DIAPH3/Drf3/Dia) assembles a dynamic F-actin cytoskeleton that underlies tumor cell migration and invasion. We therefore sought to understand whether CAF-derived chemokines impact breast tumor cell motility through modification of the formin-assembled F-actin cytoskeleton. In MDA-MB-231 cells, conditioned media (CM) from WS19T CAFs, a human breast tumor-adjacent CAF line, significantly and robustly increased wound closure and invasion relative to normal human mammary fibroblast (HMF)-CM. WS19T-CM also promoted proteasome-mediated mDia2 degradation in MDA-MB-231 cells relative to control HMF-CM and WS21T CAF-CM, a breast CAF cell line that failed to promote robust MDA-MB-231 migration. Cytokine array analysis of CM identified up-regulated secreted factors in WS19T relative to control WS21T CM. We identified CXCL12 as a CM factor influencing loss of mDia2 protein while increasing MDA-MB-231 cell migration. Our data suggest a mechanism whereby CAFs promote tumor cell migration and invasion through CXCL12 secretion to regulate the mDia2-directed cytoskeleton in breast tumor cells.

Promoter methylation assay of SASH1 gene in breast cancer.

PubMed

Sheyu, Lin; Hui, Liu; Junyu, Zhang; Jiawei, Xu; Honglian, Wang; Qing, Sang; Hengwei, Zhang; Xuhui, Guo; Qinghe, Xing; Lin, He

2013-01-01

To analyze the relationship between the expression of SASH1 and its methylation level of SASH1 gene promoter in human breast cancer. Expression levels of SASH1 were examined in breast cancer tissues and adjacent normal tissues with immunohistochemistry and with real time PCR (RT-PCR) methylation analysis was performed with MassArray. Immunohistochemistry showed that SASH1 expression was strongly reduced in breast cancer compared with adjacent normal tissues. Quantitative methylation analysis by MassArray revealed that CpG sites in SASH1 promoter shared similar methylation pattern in tumor tissue and adjacent normal tissue. The CpG sites with significant difference in methylation level were CpG_26.27 and CpG_54.55. Moreover, 5-aza-2'-deoxycytidine (5-Aza-dc) treatment of tumor cell line MDA-MB-231 caused significant elevation of SASH1 mRNA. Based on these data, we propose that increase of DNA methylation level in the promoter region of gene SASH1, particularly CpG_26.27 or CpG_54.55 sites, possibly repressed SASH1 expression in breast cancer.

Hypoxia-inducible factors regulate pluripotency factor expression by ZNF217- and ALKBH5-mediated modulation of RNA methylation in breast cancer cells.

PubMed

Zhang, Chuanzhao; Zhi, Wanqing Iris; Lu, Haiquan; Samanta, Debangshu; Chen, Ivan; Gabrielson, Edward; Semenza, Gregg L

2016-10-04

Exposure of breast cancer cells to hypoxia increases the percentage of breast cancer stem cells (BCSCs), which are required for tumor initiation and metastasis, and this response is dependent on the activity of hypoxia-inducible factors (HIFs). We previously reported that exposure of breast cancer cells to hypoxia induces the ALKBH5-mediated demethylation of N6-methyladenosine (m6A) in NANOG mRNA leading to increased expression of NANOG, which is a pluripotency factor that promotes BCSC specification. Here we report that exposure of breast cancer cells to hypoxia also induces ZNF217-dependent inhibition of m6A methylation of mRNAs encoding NANOG and KLF4, which is another pluripotency factor that mediates BCSC specification. Although hypoxia induced the BCSC phenotype in all breast-cancer cell lines analyzed, it did so through variable induction of pluripotency factors and ALKBH5 or ZNF217. However, in every breast cancer line, the hypoxic induction of pluripotency factor and ALKBH5 or ZNF217 expression was HIF-dependent. Immunohistochemistry revealed that expression of HIF-1α and ALKBH5 was concordant in all human breast cancer biopsies analyzed. ALKBH5 knockdown in MDA-MB-231 breast cancer cells significantly decreased metastasis from breast to lungs in immunodeficient mice. Thus, HIFs stimulate pluripotency factor expression and BCSC specification by negative regulation of RNA methylation.

Obesity and Breast Cancer: Current Insights on the Role of Fatty Acids and Lipid Metabolism in Promoting Breast Cancer Growth and Progression

PubMed Central

Blücher, Christina; Stadler, Sonja C.

2017-01-01

Obesity and excess accumulation of adipose tissue are known risk factors for several types of cancer, including breast cancer. With the incidence of obesity constantly rising worldwide, understanding the molecular details of the interaction between adipose tissue and breast tumors, the most common tumors in women, becomes an urgent task. In terms of lipid metabolism, most of the studies conducted so far focused on upregulated de novo lipid synthesis in cancer cells. More recently, the use of extracellular lipids as source of energy came into focus. Especially in obesity, associated dysfunctional adipose tissue releases increased amounts of fatty acids, but also dietary lipids can be involved in promoting tumor growth and progression. In addition, it was shown that breast cancer cells and adipocytes, which are a major component of the stroma of breast tumors, are able to directly interact with each other. Breast cancer cells and adjacent adipocytes exchange molecules such as growth factors, chemokines, and interleukins in a reciprocal manner. Moreover, it was shown that breast cancer cells can access and utilize fatty acids produced by neighboring adipocytes. Thus adipocytes, and especially hypertrophic adipocytes, can act as providers of lipids, which can be used as a source of energy for fatty acid oxidation and as building blocks for tumor cell growth. PMID:29163362

Clinical validation of nuclear factor kappa B expression in invasive breast cancer.

PubMed

Agrawal, Anil Kumar; Pielka, Ewa; Lipinski, Artur; Jelen, Michal; Kielan, Wojciech; Agrawal, Siddarth

2018-01-01

Breast cancer is the most commonly diagnosed cancer in Polish women. The expression of transcription nuclear factor kappa B, a key inducer of inflammatory response promoting carcinogenesis and cancer progression in breast cancer, is not well-established. We assessed the nuclear factor kappa B expression in a total of 119 invasive breast carcinomas and 25 healthy control samples and correlated this expression pattern with several clinical and pathologic parameters including histologic type and grade, tumor size, lymph node status, estrogen receptor status, and progesterone receptor status. The data used for the analysis were derived from medical records. An immunohistochemical analysis of nuclear factor kappa B, estrogen receptor, and progesterone receptor was carried out and evaluation of stainings was performed. The expression of nuclear factor kappa B was significantly higher than that in the corresponding healthy control samples. No statistical difference was demonstrated in nuclear factor kappa B expression in relation to age, menopausal status, lymph node status, tumor size and location, grade and histologic type of tumor, and hormonal status (estrogen receptor and progesterone receptor). Nuclear factor kappa B is significantly overexpressed in invasive breast cancer tissues. Although nuclear factor kappa B status does not correlate with clinicopathological findings, it might provide important additional information on prognosis and become a promising object for targeted therapy.

Factors affecting breast milk composition and potential consequences for development of the allergic phenotype.

PubMed

Munblit, D; Boyle, R J; Warner, J O

2015-03-01

There is conflicting evidence on the protective role of breastfeeding in relation to allergic sensitization and disease. The factors in breast milk which influence these processes are still unclear and under investigation. We know that colostrum and breast milk contain a variety of molecules which can influence immune responses in the gut-associated lymphoid tissue of a neonate. This review summarizes the evidence that variations in colostrum and breast milk composition can influence allergic outcomes in the infant, and the evidence that maternal and environmental factors can modify milk composition. Taken together, the data presented support the possibility that maternal dietary interventions may be an effective way to promote infant health through modification of breast milk composition. © 2014 John Wiley & Sons Ltd.

The effectiveness of a nurse-delivered breast health promotion program on breast cancer screening behaviours in non-adherent Turkish women: A randomized controlled trial.

PubMed

Secginli, Selda; Nahcivan, Nursen O

2011-01-01

Few studies have investigated breast health programs to promote rates of having a mammography, clinical breast examination and breast self-examination among non-adherent Turkish women. To determine the effectiveness of a breast health promotion program on mammography and clinical breast examination use, breast self-examination frequency and proficiency (breast self-examination skills and lump detection), breast health knowledge and health beliefs about breast cancer screening in a sample of Turkish women. Experimental (pretest-posttest control group). A community-based setting in Istanbul, Turkey. 190 Non-adherent women (intervention group=97, control group=93) aged 41 and older, residing in Istanbul, Turkey. The intervention group (n=97) received a 120-min breast health promotion program based on health belief model including a breast health education, film, breast self-examination instruction, and a booklet, a calendar, a card designed specifically for the study. The control group (n=93) received general information except breast health. Data were collected before the program, immediately after the program, and at 3- and 6-month post-program. The outcome measures are the mammography, clinical breast examination, and breast self-examination frequency, breast self-examination proficiency, breast health knowledge, and health beliefs (perceived susceptibility to breast cancer, benefits to mammography and breast self-examination, barriers of mammography and breast self-examination, confidence in performing breast self-examination). The breast health promotion program significantly increased breast self-examination frequency and proficiency and breast health knowledge. No significant differences existed in mammography and clinical breast examination rates between the two groups at 6 months. The program was effective in increasing perceived susceptibility to breast cancer, perceived benefits of mammography and breast self-examination, and confidence of breast self

A genetic polymorphism repurposes the G-protein coupled and membrane-associated estrogen receptor GPER to a transcription factor-like molecule promoting paracrine signaling between stroma and breast carcinoma cells

PubMed Central

Pupo, Marco; Bodmer, Alexandre; Berto, Melissa; Maggiolini, Marcello; Dietrich, Pierre-Yves; Picard, Didier

2017-01-01

GPER is a membrane-associated estrogen receptor of the family of G-protein coupled receptors. For breast cancer, the contribution of GPER to promoting the proliferation and migration of both carcinoma cells and cancer-associated fibroblasts (CAFs) in response to estrogen and other agonists has extensively been investigated. Intriguingly, GPER was previously found to be localized to the nucleus in one isolate of breast CAFs. Moreover, this nuclear GPER was shown to bind regulatory sequences of cancer-relevant target genes and to induce their expression. We decided to find out what induces the nuclear localization of GPER, how general this phenomenon is, and what its functional significance is. We discovered that interfering with N-linked glycosylation of GPER, either by mutation of the predicted glycosylation sites or pharmacologically with tunicamycin, drives GPER into the nucleus. Surveying a small set of CAFs from breast cancer biopsies, we found that a relatively common single nucleotide polymorphism, which results in the expression of a GPER variant with the amino acid substitution P16L, is associated with the nuclear localization of GPER. GPER with P16L fails to be glycosylated, presumably because of a conformational effect on the nearby glycosylation sites. GPER P16L is defective for membrane-associated signaling, but instead acts like an estrogen-stimulated transcription factor. In CAFs, it induces the secretion of paracrine factors that promote the migration of carcinoma cells. This raises the possibility that the GPER P16L polymorphism could be a risk factor for breast cancer. PMID:28596490

A genetic polymorphism repurposes the G-protein coupled and membrane-associated estrogen receptor GPER to a transcription factor-like molecule promoting paracrine signaling between stroma and breast carcinoma cells.

PubMed

Pupo, Marco; Bodmer, Alexandre; Berto, Melissa; Maggiolini, Marcello; Dietrich, Pierre-Yves; Picard, Didier

2017-07-18

GPER is a membrane-associated estrogen receptor of the family of G-protein coupled receptors. For breast cancer, the contribution of GPER to promoting the proliferation and migration of both carcinoma cells and cancer-associated fibroblasts (CAFs) in response to estrogen and other agonists has extensively been investigated. Intriguingly, GPER was previously found to be localized to the nucleus in one isolate of breast CAFs. Moreover, this nuclear GPER was shown to bind regulatory sequences of cancer-relevant target genes and to induce their expression. We decided to find out what induces the nuclear localization of GPER, how general this phenomenon is, and what its functional significance is. We discovered that interfering with N-linked glycosylation of GPER, either by mutation of the predicted glycosylation sites or pharmacologically with tunicamycin, drives GPER into the nucleus. Surveying a small set of CAFs from breast cancer biopsies, we found that a relatively common single nucleotide polymorphism, which results in the expression of a GPER variant with the amino acid substitution P16L, is associated with the nuclear localization of GPER. GPER with P16L fails to be glycosylated, presumably because of a conformational effect on the nearby glycosylation sites. GPER P16L is defective for membrane-associated signaling, but instead acts like an estrogen-stimulated transcription factor. In CAFs, it induces the secretion of paracrine factors that promote the migration of carcinoma cells. This raises the possibility that the GPER P16L polymorphism could be a risk factor for breast cancer.

Oxidative stress specifically downregulates survivin to promote breast tumour formation.

PubMed

Pervin, S; Tran, L; Urman, R; Braga, M; Parveen, M; Li, S A; Chaudhuri, G; Singh, R

2013-03-05

Breast cancer, a heterogeneous disease has been broadly classified into oestrogen receptor positive (ER+) or oestrogen receptor negative (ER-) tumour types. Each of these tumours is dependent on specific signalling pathways for their progression. While high levels of survivin, an anti-apoptotic protein, increases aggressive behaviour in ER- breast tumours, oxidative stress (OS) promotes the progression of ER+ breast tumours. Mechanisms and molecular targets by which OS promotes tumourigenesis remain poorly understood. DETA-NONOate, a nitric oxide (NO)-donor induces OS in breast cancer cell lines by early re-localisation and downregulation of cellular survivin. Using in vivo models of HMLE(HRAS) xenografts and E2-induced breast tumours in ACI rats, we demonstrate that high OS downregulates survivin during initiation of tumourigenesis. Overexpression of survivin in HMLE(HRAS) cells led to a significant delay in tumour initiation and tumour volume in nude mice. This inverse relationship between survivin and OS was also observed in ER+ human breast tumours. We also demonstrate an upregulation of NADPH oxidase-1 (NOX1) and its activating protein p67, which are novel markers of OS in E2-induced tumours in ACI rats and as well as in ER+ human breast tumours. Our data, therefore, suggest that downregulation of survivin could be an important early event by which OS initiates breast tumour formation.

Quantitative assessment of the association between APC promoter methylation and breast cancer.

PubMed

He, Keli; Zhang, Li; Long, Xinghua

2016-06-21

Adenomatous polyposis coli (APC) is an important tumor suppressor gene in breast cancer. However, there were inconsistent conclusions in the association between APC promoter methylation and breast cancer. Hence, we conducted a meta-analysis to quantitatively assess the clinicopathological significance and diagnosis role of APC methylation in breast cancer. In total, 3172 samples from 29 studies were performed in this study. The odds ratio (OR) of APC methylation was 5.92 (95% CI = 3.16-11.07) in breast cancer cases compared to controls,. The APC promoter methylation was associated with cancer stage (OR = 0.47, 95% CI = 0.28-0.80, P = 0.006), lymph node metastases (OR = 0.55, 95% CI = 0.36-0.84, P = 0.005) and ER status (OR = 1.34, 95% CI = 1.03-1.73, P = 0.003) in breast cancer. Furthermore, the sensitivity and specificity for all included studies were 0.444 (95% CI: 0.321-0.575, P < 0.0001) and 0.976 (95% CI: 0.916-0.993, P < 0.0001), respectively. These results suggested that APC promoter methylation was associated with breast cancer risk, and it could be a valuable biomarker for diagnosis, treatment and prognosis of breast cancer.

Knowledge, perception, practice and barriers of breast cancer health promotion activities among community pharmacists in two Districts of Selangor state, Malaysia.

PubMed

Beshir, Semira A; Hanipah, Monalina A

2012-01-01

Breast cancer is the most common cancer and the leading cause of cancer death among women in Malaysia. Despite the campaigns undertaken to raise the awareness of the public regarding breast cancer, breast cancer screening rates are still low in the country. The community pharmacist, as one of the most accessible healthcare practitioners, could play a role in the provision of breast cancer health promotion services to the community. However, there are no documented data regarding the community pharmacists' involvement in breast cancer related health promotion activities. Hence, this study was conducted to examine self-reported knowledge, practice and perception of community pharmacists on provision of breast cancer health promotion services and to investigate the barriers that limit their involvement. This cross-sectional survey conducted between May to September 2010, included a sample of 35 community pharmacists working in the districts of Hulu Langat and Sepang in state of Selangor. A 22-item validated questionnaire that included both closed and Lickert scale questions was used to interview those pharmacists who gave their informed consent to participate in the study. The data was analysed using SPSS. Only 11.3% of the community pharmacists answered all the questions on the knowledge section correctly. The mean overall knowledge of the community pharmacists on risk factors of breast cancer and screening recommendations is 56%. None of the respondents was currently involved in breast cancer health promotion activities. Lack of time (80%), lack of breast cancer educational materials (77.1%) and lack of training (62.9%) were the top three mentioned barriers. Despite these barriers, 94.3% (33) of the community pharmacists agreed that they should be involved in breast cancer health promotion activities. Hence, there is need to equip community pharmacists with necessary training and knowledge to enable them to contribute their share towards prevention and screening of

Hypermethylation of the breast cancer-associated gene 1 promoter does not predict cytologic atypia or correlate with surrogate end points of breast cancer risk.

PubMed

Bean, Gregory R; Ibarra Drendall, Catherine; Goldenberg, Vanessa K; Baker, Joseph C; Troch, Michelle M; Paisie, Carolyn; Wilke, Lee G; Yee, Lisa; Marcom, Paul K; Kimler, Bruce F; Fabian, Carol J; Zalles, Carola M; Broadwater, Gloria; Scott, Victoria; Seewaldt, Victoria L

2007-01-01

Mutation of the breast cancer-associated gene 1 (BRCA1) plays an important role in familial breast cancer. Although hypermethylation of the BRCA1 promoter has been observed in sporadic breast cancer, its exact role in breast cancer initiation and association with breast cancer risk is unknown. The frequency of BRCA1 promoter hypermethylation was tested in (a) 14 primary breast cancer biopsies and (b) the initial random periareolar fine-needle aspiration (RPFNA) cytologic samples obtained from 61 asymptomatic women who were at increased risk for breast cancer. BRCA1 promoter hypermethylation was assessed from nucleotide -150 to nucleotide +32 relative to the transcription start site. RPFNA specimens were stratified for cytologic atypia using the Masood cytology index. BRCA1 promoter hypermethylation was observed at similar frequency in nonproliferative (normal; Masood promoter hypermethylation was not associated with (a) family history of breast or ovarian cancer or (b) calculated Gail or BRCAPRO risk score. BRCA1 promoter hypermethylation was associated with (a) age (P = 0.028) and (b) the combined frequency of promoter hypermethylation of the retinoic acid receptor-beta2 (RARB) gene, estrogen receptor-alpha (ESR1) gene, and p16 (INK4A) gene (P = 0.003). These observations show that BRCA1 promoter hypermethylation (a) is not associated with breast cancer risk as measured by mathematical risk models and (b) does not predict mammary atypia in RPFNA cytologic samples obtained from high-risk women.

A randomized breast-feeding promotion intervention did not reduce child obesity in Belarus.

PubMed

Kramer, Michael S; Matush, Lidia; Vanilovich, Irina; Platt, Robert W; Bogdanovich, Natalia; Sevkovskaya, Zinaida; Dzikovich, Irina; Shishko, Gyorgy; Collet, Jean-Paul; Martin, Richard M; Smith, George Davey; Gillman, Matthew W; Chalmers, Beverley; Hodnett, Ellen; Shapiro, Stanley

2009-02-01

The evidence that breast-feeding protects against obesity is based on observational studies, with potential for confounding and selection bias. This article summarizes a previously published study in which we assessed whether an intervention designed to promote exclusive and prolonged breast-feeding affects children's height, weight, adiposity, and blood pressure (BP) at age 6.5 y. The Promotion of Breastfeeding Intervention Trial (PROBIT) is a cluster-randomized trial of a breast-feeding promotion intervention based on the WHO/UNICEF Baby-Friendly Hospital Initiative. A total of 17,046 healthy breast-fed infants were enrolled from 31 Belarussian maternity hospitals and affiliated clinics, of whom 13,889 (81.5%) were followed up at 6.5 y with duplicate measurements of height, weight, waist circumference, triceps and subscapular skinfold thicknesses, systolic and diastolic BP. Analysis was based on intention to treat, with statistical adjustment for clustering within hospitals/clinics to permit inferences at the individual level. The experimental intervention led to a large increase in exclusive breast-feeding at 3 mo (43.3% vs. 6.4%, P < 0.001) and a significantly higher prevalence of any breast-feeding throughout infancy. No significant intervention effects were observed on height, BMI, adiposity measures, or BP. The breast-feeding promotion intervention resulted in substantial increases in the duration and exclusivity of breast-feeding yet did not reduce measures of adiposity at age 6.5 y. Previous reports of protective effects against obesity may reflect uncontrolled bias caused by confounding and selection.

Comparison of telomere length and insulin-like growth factor-binding protein 7 promoter methylation between breast cancer tissues and adjacent normal tissues in Turkish women.

PubMed

Kaya, Zehra; Akkiprik, Mustafa; Karabulut, Sevgi; Peker, Irem; Gullu Amuran, Gokce; Ozmen, Tolga; Gulluoglu, Bahadır M; Kaya, Handan; Ozer, Ayse

2017-09-01

Both insulin-like growth factor-binding protein 7 (IGFBP7) and telomere length (TL) are associated with proliferation and senescence of human breast cancer. This study assessed the clinical significance of both TL and IGFBP7 methylation status in breast cancer tissues compared with adjacent normal tissues. We also investigated whether IGFBP7 methylation status could be affecting TL. Telomere length was measured by quantitative PCR to compare tumors with their adjacent normal tissues. The IGFBP7 promoter methylation status was evaluated by methylation-specific PCR and its expression levels were determined by western blotting. Telomeres were shorter in tumor tissues compared to controls (P<.0001). The mean TL was higher in breast cancer with invasive ductal carcinoma (IDC; n=72; P=.014) compared with other histological type (n=29), and TL in IDC with HER2 negative (n=53; P=.017) was higher than TL in IDC with HER2 positive (n=19). However, telomeres were shortened in advanced stages and growing tumors. IGFBP7 methylation was observed in 90% of tumor tissues and 59% of controls (P=.0002). Its frequency was significantly higher in IDC compared with invasive mixed carcinoma (IMC; P=.002) and it was not correlated either with protein expression or the other clinicopathological parameters. These results suggest that IGFBP7 promoter methylation and shorter TL in tumor compared with adjacent tissues may be predictive biomarkers for breast cancer. Telomere maintenance may be indicative of IDC and IDC with HER2 (-) of breast cancer. Further studies with larger number of cases are necessary to verify this association. © 2016 Wiley Periodicals, Inc.

HIF-inducible miR-191 promotes migration in breast cancer through complex regulation of TGFβ-signaling in hypoxic microenvironment.

PubMed

Nagpal, Neha; Ahmad, Hafiz M; Chameettachal, Shibu; Sundar, Durai; Ghosh, Sourabh; Kulshreshtha, Ritu

2015-04-13

The molecular mechanisms of hypoxia induced breast cell migration remain incompletely understood. Our results show that hypoxia through hypoxia-inducible factor (HIF) brings about a time-dependent increase in the level of an oncogenic microRNA, miR-191 in various breast cancer cell lines. miR-191 enhances breast cancer aggressiveness by promoting cell proliferation, migration and survival under hypoxia. We further established that miR-191 is a critical regulator of transforming growth factor beta (TGFβ)-signaling and promotes cell migration by inducing TGFβ2 expression under hypoxia through direct binding and indirectly by regulating levels of a RNA binding protein, human antigen R (HuR). The levels of several TGFβ pathway genes (like VEGFA, SMAD3, CTGF and BMP4) were found to be higher in miR-191 overexpressing cells. Lastly, anti-miR-191 treatment given to breast tumor spheroids led to drastic reduction in spheroid tumor volume. This stands as a first report of identification of a microRNA mediator that links hypoxia and the TGFβ signaling pathways, both of which are involved in regulation of breast cancer metastasis. Together, our results show a critical role of miR-191 in hypoxia-induced cancer progression and suggest that miR-191 inhibition may offer a novel therapy for hypoxic breast tumors.

Hybrid promoters directed tBid gene expression to breast cancer cells by transcriptional targeting.

PubMed

Farokhimanesh, Samila; Rahbarizadeh, Fatemeh; Rasaee, Mohammad J; Kamali, Abbas; Mashkani, Baratali

2010-01-01

Developing cancer gene therapy constructs based on transcriptional targeting of genes to cancer cells is a new and promising modality for treatment of cancer. Introducing truncated Bid (tBid), a recently known member of the Bcl-2 family, eradicates cancer cells efficiently. For transcriptional targeting of tBid, two dual-specificity promoters, combining cancer specific core promoters and response modules, were designed. These two core promoter modules contained cancer specific promoters of MUC1 and Survivin genes accompanied by hypoxia-responsive elements and estrogen responsive elements (microenvironment condition of breast cancer cells) which were employed to achieve a higher and more specific level of tBid expression in breast cancer cells. Correlation of the level of tBid expression in normal and cancer cell lines with promoter activity was measured by RT-PCR after treatment with hypoxia and estrogen. The level of tBid expression under control of new hybrid promoters was compared with its expression under control of cytomegalovirus (CMV) promoter as a control. Our data revealed that the level of tBid expression in breast cancer cells were nearly 11 times more than normal cells because of the cancer specific promoters, although tBid expression under control of CMV promoter was almost the same in normal and cancer cell lines. Increased apoptosis was detected in the transfected breast cancer cell lines by the Caspase-3 activity assay. The application of these promoters may prove to have the advantage of tumor selective gene therapy in breast cancer cells and low-potential toxicity for normal tissues.

Loss of epigenetic Kruppel-like factor 4 histone deacetylase (KLF-4-HDAC)-mediated transcriptional suppression is crucial in increasing vascular endothelial growth factor (VEGF) expression in breast cancer.

PubMed

Ray, Alpana; Alalem, Mohamed; Ray, Bimal K

2013-09-20

Vascular endothelial growth factor (VEGF) is recognized as an important angiogenic factor that promotes angiogenesis in a series of pathological conditions, including cancer, inflammation, and ischemic disorders. We have recently shown that the inflammatory transcription factor SAF-1 is, at least in part, responsible for the marked increase of VEGF levels in breast cancer. Here, we show that SAF-1-mediated induction of VEGF is repressed by KLF-4 transcription factor. KLF-4 is abundantly present in normal breast epithelial cells, but its level is considerably reduced in breast cancer cells and clinical cancer tissues. In the human VEGF promoter, SAF-1- and KLF-4-binding elements are overlapping, whereas SAF-1 induces and KLF-4 suppresses VEGF expression. Ectopic overexpression of KLF-4 and RNAi-mediated inhibition of endogenous KLF-4 supported the role of KLF-4 as a transcriptional repressor of VEGF and an inhibitor of angiogenesis in breast cancer cells. We show that KLF-4 recruits histone deacetylases (HDACs) -2 and -3 at the VEGF promoter. Chronological ChIP assays demonstrated the occupancy of KLF-4, HDAC2, and HDAC3 in the VEGF promoter in normal MCF-10A cells but not in MDA-MB-231 cancer cells. Co-transfection of KLF-4 and HDAC expression plasmids in breast cancer cells results in synergistic repression of VEGF expression and inhibition of angiogenic potential of these carcinoma cells. Together these results identify a new mechanism of VEGF up-regulation in cancer that involves concomitant loss of KLF-4-HDAC-mediated transcriptional repression and active recruitment of SAF-1-mediated transcriptional activation.

Breast-feeding patterns and factors determining exclusive breast-feeding.

PubMed

Koosha, A; Hashemifesharaki, R; Mousavinasab, N

2008-12-01

Breast-feeding is a major determinant of infants' health and survival. The aim of this study was to examine breast-feeding patterns and the role of some factors on exclusive breast-feeding. The study was done at the Health Centre of Community Oriented Medical Education of Zanjan City, Iran. Mothers of 650 infants younger than one year of age were interviewed directly by healthcare providers. The necessary information was recorded on pre-structured questionnaires, and the feeding patterns of all infants were determined. The rate of breast-feeding was greater than 92 percent during the first year of life. Exclusive breast-feeding rate in the first five days of life was 82 percent, but it declined to 44 percent at the first month. The chance of exclusive breast-feeding was higher in infants who were on demand feeding (odds ratio [OR] 2.6), breastfed more than eight times per day (OR 2.23), and their birth weight ranged from 2.5 to 4 kg (OR 2.16). This chance was less among infants exposed to pacifiers (OR 2.62) and with the numbers of deliveries equal to or more than three (OR 2.25). The rates of breast-feeding initiation and its duration at six and 12 months were higher than the national goal. The rate of exclusive breast-feeding was nearly 44 percent. It seems necessary to elucidate the role of other factors, such as socioeconomic status, on exclusive breast-feeding.

CREB-1 and AP-1 transcription factors JunD and Fra-2 regulate bone sialoprotein gene expression in human breast cancer cells.

PubMed

Detry, C; Lamour, V; Castronovo, V; Bellahcène, A

2008-02-01

Bone sialoprotein (BSP) expression is detected in a variety of human osteotropic cancers. High expression of BSP in breast and prostate primary carcinomas is associated with progression and bone metastases development. In this study, we examined the transcriptional regulation of BSP gene expression in MDA-MB-231 and MCF-7 human breast cancer cells compared with Saos-2 human osteoblast-like cells. BSP human promoter deletion analyses delineated a -56/-84 region, which comprises a cAMP response element (CRE) that was sufficient for maximal promoter activity in breast cancer cell lines. We found that the basic fibroblast growth factor response element (FRE) also located in the proximal promoter was a crucial regulator of human BSP promoter activity in Saos-2 but not in breast cancer cells. Promoter activity experiments in combination with DNA mobility shift assays demonstrated that BSP promoter activity is under the control of the CRE element, through CREB-1, JunD and Fra-2 binding, in MDA-MB-231, MCF-7 and in Saos-2 cells. Forskolin, a protein kinase A pathway activator, failed to enhance BSP transcriptional activity suggesting that CRE site behaves as a constitutive rather than an inducible element in these cell lines. Over-expression of JunD and Fra-2 increased BSP promoter activity and upregulated endogenous BSP protein expression in MCF-7 and Saos-2 cells while siRNA-mediated inhibition of both factors expression significantly reduced BSP protein level in MDA-MB-231. Collectively, these data provide with new transcriptional mechanisms, implicating CREB and AP-1 factors, that control BSP gene expression in breast cancer cells.

BAG3 promotes stem cell-like phenotype in breast cancer by upregulation of CXCR4 via interaction with its transcript.

PubMed

Liu, Bao-Qin; Zhang, Song; Li, Si; An, Ming-Xin; Li, Chao; Yan, Jing; Wang, Jia-Mei; Wang, Hua-Qin

2017-07-13

BAG3 is an evolutionarily conserved co-chaperone expressed at high levels and has a prosurvival role in many tumor types. The current study reported that BAG3 was induced under specific floating culture conditions that enrich breast cancer stem cell (BCSC)-like cells in spheres. Ectopic BAG3 overexpression increased CD44 + /CD24 - CSC subpopulations, first-generation and second-generation mammosphere formation, indicating that BAG3 promotes CSC self-renewal and maintenance in breast cancer. We further demonstrated that mechanically, BAG3 upregulated CXCR4 expression at the post-transcriptional level. Further studies showed that BAG3 interacted with CXCR4 mRNA and promoted its expression via its coding and 3'-untranslational regions. BAG3 was also found to be positively correlated with CXCR4 expression and unfavorable prognosis in patients with breast cancer. Taken together, our data demonstrate that BAG3 promotes BCSC-like phenotype through CXCR4 via interaction with its transcript. Therefore, this study establishes BAG3 as a potential adverse prognostic factor and a therapeutic target of breast cancer.

BAG3 promotes stem cell-like phenotype in breast cancer by upregulation of CXCR4 via interaction with its transcript

PubMed Central

Liu, Bao-Qin; Zhang, Song; Li, Si; An, Ming-Xin; Li, Chao; Yan, Jing; Wang, Jia-Mei; Wang, Hua-Qin

2017-01-01

BAG3 is an evolutionarily conserved co-chaperone expressed at high levels and has a prosurvival role in many tumor types. The current study reported that BAG3 was induced under specific floating culture conditions that enrich breast cancer stem cell (BCSC)-like cells in spheres. Ectopic BAG3 overexpression increased CD44+/CD24− CSC subpopulations, first-generation and second-generation mammosphere formation, indicating that BAG3 promotes CSC self-renewal and maintenance in breast cancer. We further demonstrated that mechanically, BAG3 upregulated CXCR4 expression at the post-transcriptional level. Further studies showed that BAG3 interacted with CXCR4 mRNA and promoted its expression via its coding and 3′-untranslational regions. BAG3 was also found to be positively correlated with CXCR4 expression and unfavorable prognosis in patients with breast cancer. Taken together, our data demonstrate that BAG3 promotes BCSC-like phenotype through CXCR4 via interaction with its transcript. Therefore, this study establishes BAG3 as a potential adverse prognostic factor and a therapeutic target of breast cancer. PMID:28703799

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

PubMed

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

[Do Italian university birthing centers promote starting breast-feeding?].

PubMed

Donati, Serena; Andreozzi, Silvia; Grandolfo, Michele E

2003-01-01

This study reports the results of an Italian sampling survey carried out in 1999 on the evaluation of the support and the information activities offered to women who delivered with specific regard to breast-feeding. 1986 women have been interviewed. The response rate was 95%. Ninety-four percent of the sample reported a positive attitude among breast-feeding, but only 80% breastfed her baby during hospital stay. Moreover only 31% had the opportunity to start breast-feeding immediately after birth. Around 50% of women reported the quality of the hospital support as inadequate. The authors conclude that, even in the light of the present Italian law, much more could and should be done in order to promote and support women in breast-feeding.

HPV16 E6 Promotes Breast Cancer Proliferation via Upregulation of COX-2 Expression

PubMed Central

Li, Y. Z.; Zhang, Z. Y.; Wang, J. Q.

2017-01-01

Background. Breast cancer remains the leading cause of cancer-related mortality worldwide. It has been indicated that human papillomaviruses 16 (HPV16) might participate in the pathogenesis and development of breast cancer. However, the detected rate of HPV16 varies with region. We will investigate HPV16 E6 expression in North China and explore the effects and mechanism of HPV16 E6 on breast cancer proliferation in this study. Methods. The expressions of HPV16 E6 and COX-2 in paraffin-embedded tissues of the invasive ductal breast cancer were detected by qPCR and IHC. The effects of HPV16 E6 on breast cancer proliferation were determined by function studies. The mechanism of HPV16 E6 in promoting breast cancer proliferation was explored by Western blot and Dual-Luciferase Reporter Assay. Results. HPV16 E6 was positive in 28% invasive ductal breast carcinoma in North China; HPV16 E6 promoted breast cancer proliferation. Inhibition of COX-2 by siCOX-2 or Celecoxib attenuated the proliferation of breast cancer cells with HPV16 E6 expression; and the upregulation of COX-2 could be suppressed by the inhibition of NF-κB activity. Conclusion. HPV16 E6 promotes breast cancer proliferation by activation of NF-κB signaling pathway and increase of COX-2 expression. COX-2 will be a potential target for HPV16 E6-associated breast cancer. PMID:29250535

Transgelin gene is frequently downregulated by promoter DNA hypermethylation in breast cancer.

PubMed

Sayar, Nilufer; Karahan, Gurbet; Konu, Ozlen; Bozkurt, Betul; Bozdogan, Onder; Yulug, Isik G

2015-01-01

CpG hypermethylation in gene promoters is a frequent mechanism of tumor suppressor gene silencing in various types of cancers. It usually occurs at early steps of cancer progression and can be detected easily, giving rise to development of promising biomarkers for both detection and progression of cancer, including breast cancer. 5-aza-2'-deoxycytidine (AZA) is a DNA demethylating and anti-cancer agent resulting in induction of genes suppressed via DNA hypermethylation. Using microarray expression profiling of AZA- or DMSO-treated breast cancer and non-tumorigenic breast (NTB) cells, we identified for the first time TAGLN gene as a target of DNA hypermethylation in breast cancer. TAGLN expression was significantly and frequently downregulated via promoter DNA hypermethylation in breast cancer cells compared to NTB cells, and also in 13/21 (61.9 %) of breast tumors compared to matched normal tissues. Analyses of public microarray methylation data showed that TAGLN was also hypermethylated in 63.02 % of tumors compared to normal tissues; relapse-free survival of patients was worse with higher TAGLN methylation; and methylation levels could discriminate between tumors and healthy tissues with 83.14 % sensitivity and 100 % specificity. Additionally, qRT-PCR and immunohistochemistry experiments showed that TAGLN expression was significantly downregulated in two more independent sets of breast tumors compared to normal tissues and was lower in tumors with poor prognosis. Colony formation was increased in TAGLN silenced NTB cells, while decreased in overexpressing BC cells. TAGLN gene is frequently downregulated by DNA hypermethylation, and TAGLN promoter methylation profiles could serve as a future diagnostic biomarker, with possible clinical impact regarding the prognosis in breast cancer.

Electromechanical Coupling Factor of Breast Tissue as a Biomarker for Breast Cancer.

PubMed

Park, Kihan; Chen, Wenjin; Chekmareva, Marina A; Foran, David J; Desai, Jaydev P

2018-01-01

This research aims to validate a new biomarker of breast cancer by introducing electromechanical coupling factor of breast tissue samples as a possible additional indicator of breast cancer. Since collagen fibril exhibits a structural organization that gives rise to a piezoelectric effect, the difference in collagen density between normal and cancerous tissue can be captured by identifying the corresponding electromechanical coupling factor. The design of a portable diagnostic tool and a microelectromechanical systems (MEMS)-based biochip, which is integrated with a piezoresistive sensing layer for measuring the reaction force as well as a microheater for temperature control, is introduced. To verify that electromechanical coupling factor can be used as a biomarker for breast cancer, the piezoelectric model for breast tissue is described with preliminary experimental results on five sets of normal and invasive ductal carcinoma (IDC) samples in the 25-45 temperature range. While the stiffness of breast tissues can be captured as a representative mechanical signature which allows one to discriminate among tissue types especially in the higher strain region, the electromechanical coupling factor shows more distinct differences between the normal and IDC groups over the entire strain region than the mechanical signature. From the two-sample -test, the electromechanical coupling factor under compression shows statistically significant differences ( 0.0039) between the two groups. The increase in collagen density in breast tissue is an objective and reproducible characteristic of breast cancer. Although characterization of mechanical tissue property has been shown to be useful for differentiating cancerous tissue from normal tissue, using a single parameter may not be sufficient for practical usage due to inherent variation among biological samples. The portable breast cancer diagnostic tool reported in this manuscript shows the feasibility of measuring multiple

CpG methylation of APC promoter 1A in sporadic and familial breast cancer patients.

PubMed

Debouki-Joudi, Saoussen; Trifa, Fatma; Khabir, Abdelmajid; Sellami-Boudawara, Tahia; Frikha, Mounir; Daoud, Jamel; Mokdad-Gargouri, Raja

2017-01-01

Tumour suppressor gene (TSG) silencing through promoter hypermethylation plays an important role in cancer initiation. The aim of this study was to assess the extent of methylation of APC gene promoter in 91 sporadic and 44 familial cases of Tunisian patients with breast cancer (BC) in. The frequency of APC promoter methylation is somewhat similar for sporadic and familial breast cancer cases, (52.1%, and 54.5% respectively). For sporadic breast cancer patients, there was a significant correlation of APC promoter hypermethylation with TNM stage (p = 0.024) and 3-year survival (p = 0.025). Regarding the hormonal status (HR), we found significant association between negativity to PR and unmethylated APC (p= 0.005) while ER and Her2/neu are not correlated. Moreover, unmethylated APC promoter is more frequent in tumours expressing at least one out the 3 proteins compared to triple negative cases (p= 0.053). On the other hand, aberrant methylation of APC was associated with tumour size (p = 0.036), lymph node (p = 0.028), distant metastasis (p = 0.031), and 3-year survival (p = 0.046) in the group of patients with familial breast cancer. Moreover, patients with sporadic breast cancer displaying the unmethylated profile have a significant prolonged overall survival compared to those with the methylated pattern of APC promoter (p log rank = 0.008). Epigenetic change at the CpG islands in the APC promoter was associated with the silence of its transcript and the loss of protein expression suggesting that this event is the main mechanism regulating the APC expression in breast cancer. In conclusion, our data showed that the loss of APC through aberrant methylation is associated with the aggressive behavior of both sporadic and familial breast cancer in Tunisian patients.

Breast-feeding in South Korea: factors influencing its initiation and duration.

PubMed

Chung, Woojin; Kim, Hanjoong; Nam, Chung-Mo

2008-03-01

To investigate factors influencing the practices of partial breast-feeding (PBF) and exclusive breast-feeding (EBF). A national, cross-sectional survey was conducted among married women aged 15-49 years from May to August 2003. South Korea. A total of 865 mothers answered questions regarding the feeding practices of their youngest baby, born between January 2001 and May 2003. The initiation rates of PBF and EBF were 81% and 63%, respectively. However, the median durations of PBF and EBF were very short: 12 and 8 weeks, respectively. According to stepwise logistic and Cox regression analyses, the more prenatal care women received, the more likely they were to initiate PBF and EBF but the less likely to continue EBF. Delivery by Caesarean section decreased the initiation of PBF and EBF. The mother's education level and employment status before marriage, the amount of prenatal care, delivery method and baby's status at birth affected breast-feeding initiation, whereas the amount of prenatal care influenced breast-feeding duration. To promote breast-feeding, education and campaigning on the importance of continued breast-feeding should be provided to the general public, particularly to health workers in maternity units.

microRNA-200c/141 upregulates SerpinB2 to promote breast cancer cell metastasis and reduce patient survival.

PubMed

Jin, Tiefeng; Suk Kim, Hoe; Ki Choi, Sul; Hye Hwang, Eun; Woo, Jisu; Suk Ryu, Han; Kim, Kwangsoo; Moon, Aree; Kyung Moon, Woo

2017-05-16

The microRNA-200 (miR-200) family is associated with tumor metastasis and poor patient prognosis. We found that miR-200c/141 cluster overexpression upregulated SerpinB2 in the MDA-MB-231 triple-negative (TN) breast cancer cell line. We observed transcription factor (c-Jun, c-Fos, and FosB) upregulation, nuclear localization of c-Jun, and increased SerpinB2 promoter-directed chloramphenicol acetyltransferase activity in miR-200c/141 cluster-overexpressing cells relative to controls. Additionally, miR-124a and miR-26b, which directly target SepinB2, were downregulated compared to controls. In mouse xenograft models, miR-200c/141 cluster overexpression promoted lymph node and lung metastasis, and siRNA-mediated SerpinB2 knockdown decreased lung metastasis, suggesting that SerpinB2 mediates miR-200c/141-induced lung metastasis. We also explored the clinical significance of SerpinB2 protein status through analysis of primary breast tumor samples and The Cancer Genome Atlas (TCGA) data. High SerpinB2 levels were associated with reduced survival and increased lymph node metastasis in breast cancer patients. SerpinB2 was overexpressed in the TN breast cancer subtype as compared to the luminal subtype. The present study demonstrates that SerpinB2 promotes miR-200c/141 cluster overexpression-induced breast cancer cell metastasis, and SerpinB2 overexpression correlates with increased metastatic potential and unfavorable outcomes in breast cancer patients. SerpinB2 may be a useful biomarker for assessing metastasis risk in breast cancer patients.

Downregulation of CXCL12 in mesenchymal stromal cells by TGFβ promotes breast cancer metastasis.

PubMed

Yu, P F; Huang, Y; Xu, C L; Lin, L Y; Han, Y Y; Sun, W H; Hu, G H; Rabson, A B; Wang, Y; Shi, Y F

2017-02-09

Mesenchymal stromal cells (MSCs) are one of major components of the tumour microenvironment. Recent studies have shown that MSC tumour residence and their close interactions with inflammatory factors are important factors that affect tumour progression. Among tumour-associated inflammatory factors, transforming growth factor β (TGFβ) is regarded as a key determinant of malignancy. By employing a lung metastasis model of a murine breast cancer, we show here that the prometastatic effect of MSCs was dependent on their response to TGFβ. Interestingly, we found that MSC-produced CXCL12, an important chemokine in tumour metastasis, was markedly inhibited by TGFβ. Furthermore, silencing of CXCL12 in TGFβ-unresponsive MSCs restored their ability to promote tumour metastasis. We found that 4T1 breast cancer cells expressed high levels of CXCR7, but not of CXCR4, both of which are CXCL12 receptors. In presence of CXCL12, CXCR7 expression on tumour cells was decreased. Indeed, when CXCR7 was silenced in breast cancer cells, their metastatic ability was inhibited. Therefore, our data demonstrated that sustained expression of CXCL12 by MSCs in the primary tumour site inhibits metastasis through reduction of CXCR7, while, in the presence of TGFβ, this CXCL12 effect of MSCs on tumour cells is relieved. Importantly, elevated CXCR7 and depressed CXCL12 expression levels were prominent features of clinical breast cancer lesions and were related significantly with poor survival. Our findings reveal a novel mechanism of MSC effects on malignant cells through which crosstalk between MSCs and TGFβ regulates tumour metastasis.

Clinical Breast Examination As the Recommended Breast Cancer Screening Modality in a Rural Community in Malaysia; What Are the Factors That Could Enhance Its Uptake?

PubMed Central

Nik Farid, Nik Daliana; Abdul Aziz, Norlaili; Al-Sadat, Nabilla; Jamaludin, Mariam; Dahlui, Maznah

2014-01-01

Breast cancer is the most common cause of deaths and the most frequently diagnosed cancer among women worldwide. This study aimed to determine the prevalence of breast cancer screening, specifically on clinical breast examination, and the predictors of its uptake among women in Malaysia. A cross-sectional study was carried out in five selected districts whereby women aged between 20 to 64 years old, from a total of 1000 households were interviewed. A total of 1192 women responded to the survey of which 53.3% reported had ever done clinical breast examination. Significant associations with clinical breast examination were noted for income and distance from the hospital. These factors should be considered in developing interventions aimed at promoting clinical breast examination. In particular, healthcare providers should be proactive in raising awareness about clinical breast examination among women in Malaysia. PMID:25188003

Factors affecting breast-feeding initiation in Greece: What is important?

PubMed

Tavoulari, Evangelia-Filothei; Benetou, Vassiliki; Vlastarakos, Petros V; Andriopoulou, Eirini; Kreatsas, George; Linos, Athena

2015-02-01

to investigate the association between breast-feeding initiation and socio-demographic, lifestyle-related, clinical and lactation-related factors in a sample of mothers living in Greece. cross-sectional study. Tertiary University Hospital, maternity ward. 428 mothers were interviewed (43.2% response rate) from February until December 2009, using a structured face-to-face questionnaire after at least 24 hours from childbirth. 71.0% of mothers were Greeks and 29.0% immigrants; the mean age was 32.0 years. 44.4% initiated exclusive breast feeding, 7.9% artificial milk -feeding and 47.7% partial feeding. In the multivariate analysis, exclusive breast feeding was inversely related to maternal body mass index (BMI) at the beginning of gestation (odds ratio (OR)=0.93, 95% confidence intervals (95%CI)=0.89-0.98) and caesarean section (OR=0.54, 95% CI=0.35-0.84). Lactation-related factors which favourably affected exclusive breast-feeding initiation included previous breast-feeding experience (OR=2.29, 95% CI=1.39-3.78), information about breast feeding (OR=2.38, 95% CI=1.41-4.01) and rooming-in (OR=1.62 95% CI=1.03-2.54), whilst any breast feeding was favourably affected by encouraging women to breast feed (OR=5.42, 95% CI=1.90-15.50), providing information about breast feeding (OR=6.92, 95% CI=2.53-18.89), and rooming-in (OR=6.93 95% CI=2.01-23.88), and negatively associated with caesarean section (OR=0.11, 95% CI=0.03-0.39). Being an immigrant mother was also positively associated with any breast-feeding initiation (OR=7.97, 95% CI=1.02-62.19). Maternal age, education and income, as well as, smoking status, were not associated with any breast-feeding initiation. maternal BMI and immigrant status, information provided by midwives and encouragement, rooming-in and mode of childbirth (caesarean section), were found to be important for breast-feeding initiation in this study population. No other indicator of socio-demographic status was found to be associated with breast

PKCλ/ι signaling promotes triple-negative breast cancer growth and metastasis.

PubMed

Paul, A; Gunewardena, S; Stecklein, S R; Saha, B; Parelkar, N; Danley, M; Rajendran, G; Home, P; Ray, S; Jokar, I; Vielhauer, G A; Jensen, R A; Tawfik, O; Paul, S

2014-09-01

Triple-negative breast cancer (TNBC) is a distinct breast cancer subtype defined by the absence of estrogen receptor (ER), progesterone receptor (PR) and epidermal growth factor receptor 2 (HER2/neu), and the patients with TNBC are often diagnosed with higher rates of recurrence and metastasis. Because of the absence of ER, PR and HER2/neu expressions, TNBC patients are insensitive to HER2-directed and endocrine therapies available for breast cancer treatment. Here, we report that expression of atypical protein kinase C isoform, PKCλ/ι, significantly increased and activated in all invasive breast cancer (invasive ductal carcinoma or IDC) subtypes including the TNBC subtype. Because of the lack of targeted therapies for TNBC, we choose to study PKCλ/ι signaling as a potential therapeutic target for TNBC. Our observations indicated that PKCλ/ι signaling is highly active during breast cancer invasive progression, and metastatic breast cancers, the advanced stages of breast cancer disease that developed more frequently in TNBC patients, are also characterized with high levels of PKCλ/ι expression and activation. Functional analysis in experimental mouse models revealed that depletion of PKCλ/ι significantly reduces TNBC growth as well as lung metastatic colonization. Furthermore, we have identified a PKCλ/ι-regulated gene signature consisting of 110 genes, which are significantly associated with indolent to invasive progression of human breast cancer and poor prognosis. Mechanistically, cytokines such as TGFβ and IL1β could activate PKCλ/ι signaling in TNBC cells and depletion of PKCλ/ι impairs NF-κB p65 (RelA) nuclear localization. We observed that cytokine-PKCλ/ι-RelA signaling axis, at least in part, involved in modulating gene expression to regulate invasion of TNBC cells. Overall, our results indicate that induction and activation of PKCλ/ι promote TNBC growth, invasion and metastasis. Thus, targeting PKCλ/ι signaling could be a

PKCλ/ι signaling promotes triple-negative breast cancer growth and metastasis

PubMed Central

Paul, A; Gunewardena, S; Stecklein, S R; Saha, B; Parelkar, N; Danley, M; Rajendran, G; Home, P; Ray, S; Jokar, I; Vielhauer, G A; Jensen, R A; Tawfik, O; Paul, S

2014-01-01

Triple-negative breast cancer (TNBC) is a distinct breast cancer subtype defined by the absence of estrogen receptor (ER), progesterone receptor (PR) and epidermal growth factor receptor 2 (HER2/neu), and the patients with TNBC are often diagnosed with higher rates of recurrence and metastasis. Because of the absence of ER, PR and HER2/neu expressions, TNBC patients are insensitive to HER2-directed and endocrine therapies available for breast cancer treatment. Here, we report that expression of atypical protein kinase C isoform, PKCλ/ι, significantly increased and activated in all invasive breast cancer (invasive ductal carcinoma or IDC) subtypes including the TNBC subtype. Because of the lack of targeted therapies for TNBC, we choose to study PKCλ/ι signaling as a potential therapeutic target for TNBC. Our observations indicated that PKCλ/ι signaling is highly active during breast cancer invasive progression, and metastatic breast cancers, the advanced stages of breast cancer disease that developed more frequently in TNBC patients, are also characterized with high levels of PKCλ/ι expression and activation. Functional analysis in experimental mouse models revealed that depletion of PKCλ/ι significantly reduces TNBC growth as well as lung metastatic colonization. Furthermore, we have identified a PKCλ/ι-regulated gene signature consisting of 110 genes, which are significantly associated with indolent to invasive progression of human breast cancer and poor prognosis. Mechanistically, cytokines such as TGFβ and IL1β could activate PKCλ/ι signaling in TNBC cells and depletion of PKCλ/ι impairs NF-κB p65 (RelA) nuclear localization. We observed that cytokine-PKCλ/ι-RelA signaling axis, at least in part, involved in modulating gene expression to regulate invasion of TNBC cells. Overall, our results indicate that induction and activation of PKCλ/ι promote TNBC growth, invasion and metastasis. Thus, targeting PKCλ/ι signaling could be a

'Controversy'. Propaganda versus evidence based health promotion: the case of breast screening.

PubMed

Hann, A

1999-01-01

Breast cancer is a serious problem in the developed world, and the common perception of the risks of developing the disease are communicated to the public via a variety of means. This includes leaflets in doctors' surgeries, health promotion campaigns and invitations from well woman clinics to attend for various forms of screening. The national breast cancer screening programme in the UK has a very high compliance rate (which is vital) and a well oiled media machine. This article examines the way in which the risks of developing breast cancer are communicated to women of all ages in the UK, and speculates as to the reason behind the misleading manner in which health promoters offer this information.

Cancer Associated Fibroblasts express pro-inflammatory factors in human breast and ovarian tumors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Erez, Neta, E-mail: netaerez@post.tau.ac.il; Glanz, Sarah; Raz, Yael

Highlights: •CAFs in human breast and ovarian tumors express pro-inflammatory factors. •Expression of pro-inflammatory factors correlates with tumor invasiveness. •Expression of pro-inflammatory factors is associated with NF-κb activation in CAFs. -- Abstract: Inflammation has been established in recent years as a hallmark of cancer. Cancer Associated Fibroblasts (CAFs) support tumorigenesis by stimulating angiogenesis, cancer cell proliferation and invasion. We previously demonstrated that CAFs also mediate tumor-enhancing inflammation in a mouse model of skin carcinoma. Breast and ovarian carcinomas are amongst the leading causes of cancer-related mortality in women and cancer-related inflammation is linked with both these tumor types. However, themore » role of CAFs in mediating inflammation in these malignancies remains obscure. Here we show that CAFs in human breast and ovarian tumors express high levels of the pro-inflammatory factors IL-6, COX-2 and CXCL1, previously identified to be part of a CAF pro-inflammatory gene signature. Moreover, we show that both pro-inflammatory signaling by CAFs and leukocyte infiltration of tumors are enhanced in invasive ductal carcinoma as compared with ductal carcinoma in situ. The pro-inflammatory genes expressed by CAFs are known NF-κB targets and we show that NF-κB is up-regulated in breast and ovarian CAFs. Our data imply that CAFs mediate tumor-promoting inflammation in human breast and ovarian tumors and thus may be an attractive target for stromal-directed therapeutics.« less

NCOA1 promotes angiogenesis in breast tumors by simultaneously enhancing both HIF1α- and AP-1-mediated VEGFa transcription

PubMed Central

Qin, Li; Xu, Yan; Xu, Yixiang; Ma, Gang; Liao, Lan; Wu, Yelin; Li, Yi; Wang, Xian; Wang, Xiaosong; Jiang, Jun; Wang, Jin; Xu, Jianming

2015-01-01

Nuclear receptor coactivator 1 (NCOA1) is overexpressed in a subset of breast cancer and its increased expression positively correlates with disease recurrence and metastasis. Although NCOA1 is known to promote breast cancer metastasis through working with multiple transcription factors to upregulate the expression of Twist1, ITGA5, CSF-1, SDF1 and CXCR4, the role of NCOA1 in breast tumor angiogenesis has not been investigated. In this study, we found that the microvascular density (MVD) was significantly decreased and increased in Ncoa1-knockout and NCOA1-overexpressing mammary tumors, respectively, in several breast cancer mouse models. Knockout or knockdown of NCOA1 in breast cancer cell lines also markedly compromised their capability to induce angiogenesis in Matrigel plugs embedded subcutaneously in mice, while this compromised capability could be rescued by VEGFa treatment. At the molecular level, NCOA1 upregulates VEGFa expression in both mouse mammary tumors and cultured breast cancer cells, and it does so by associating with both c-Fos, which is recruited to the AP-1 site at bp −938 of the VEGFa promoter, and HIF1α, which is recruited to the HIF1α-binding element at bp −979 of the VEGFa promoter, to enhance VEGFa transcription. In 140 human breast tumors, high NCOA1 protein correlates with high MVD and patients with both high NCOA1 and high MVD showed significantly shorter survival time. In summary, this study revealed a novel mechanism that NCOA1 potentiates breast cancer angiogenesis through upregulating HIF1α and AP-1-mediated VEGFa expression, which reinforces the rational of targeting NCOA1 in controlling breast cancer progression and metastasis. PMID:26287601

Emodin inhibits breast cancer growth by blocking the tumor-promoting feedforward loop between cancer cells and macrophages

PubMed Central

Iwanowycz, Stephen; Wang, Junfeng; Hodge, Johnie; Wang, Yuzhen; Yu, Fang; Fan, Daping

2016-01-01

Macrophage infiltration correlates with severity in many types of cancer. Tumor cells recruit macrophages and educate them to adopt an M2-like phenotype through the secretion of chemokines and growth factors, such as MCP1 and CSF1. Macrophages in turn promote tumor growth through supporting angiogenesis, suppressing anti-tumor immunity, modulating extracellular matrix remodeling, and promoting tumor cell migration. Thus tumor cells and macrophages interact to create a feedforward loop supporting tumor growth and metastasis. In this study, we tested the ability of emodin, a Chinese herb-derived compound, to inhibit breast cancer growth in mice and examined the underlying mechanisms. Emodin was used to treat mice bearing EO771 or 4T1 breast tumors. It was shown that emodin attenuated tumor growth by inhibiting macrophage infiltration and M2-like polarization, accompanied by increased T cell activation and reduced angiogenesis in tumors. The tumor inhibitory effects of emodin were lost in tumor-bearing mice with macrophage depletion. Emodin inhibited IRF4, STAT6, and C/EBPβ signaling and increased inhibitory histone H3 lysine 27 tri-methylation (H3K27m3) on the promoters of M2 related genes in tumor-associated macrophages. In addition, emodin inhibited tumor cell secretion of MCP1and CSF1, as well as expression of surface anchoring molecule Thy-1, thus suppressing macrophage migration towards and adhesion to tumor cells. These results suggest that emodin acts on both breast cancer cells and macrophages and effectively blocks the tumor-promoting feedforward loop between the two cell types, thereby inhibiting breast cancer growth and metastasis. PMID:27196773

H19/let-7/LIN28 reciprocal negative regulatory circuit promotes breast cancer stem cell maintenance

PubMed Central

Peng, Fei; Li, Ting-Ting; Wang, Kai-Li; Xiao, Guo-Qing; Wang, Ju-Hong; Zhao, Hai-Dong; Kang, Zhi-Jie; Fan, Wen-Jun; Zhu, Li-Li; Li, Mei; Cui, Bai; Zheng, Fei-Meng; Wang, Hong-Jiang; Lam, Eric W-F; Wang, Bo; Xu, Jie; Liu, Quentin

2017-01-01

Long noncoding RNA-H19 (H19), an imprinted oncofetal gene, has a central role in carcinogenesis. Hitherto, the mechanism by which H19 regulates cancer stem cells, remains elusive. Here we show that breast cancer stem cells (BCSCs) express high levels of H19, and ectopic overexpression of H19 significantly promotes breast cancer cell clonogenicity, migration and mammosphere-forming ability. Conversely, silencing of H19 represses these BCSC properties. In concordance, knockdown of H19 markedly inhibits tumor growth and suppresses tumorigenesis in nude mice. Mechanistically, we found that H19 functions as a competing endogenous RNA to sponge miRNA let-7, leading to an increase in expression of a let-7 target, the core pluripotency factor LIN28, which is enriched in BCSC populations and breast patient samples. Intriguingly, this gain of LIN28 expression can also feedback to reverse the H19 loss-mediated suppression of BCSC properties. Our data also reveal that LIN28 blocks mature let-7 production and, thereby, de-represses H19 expression in breast cancer cells. Appropriately, H19 and LIN28 expression exhibits strong correlations in primary breast carcinomas. Collectively, these findings reveal that lncRNA H19, miRNA let-7 and transcriptional factor LIN28 form a double-negative feedback loop, which has a critical role in the maintenance of BCSCs. Consequently, disrupting this pathway provides a novel therapeutic strategy for breast cancer. PMID:28102845

Promoting early presentation of breast cancer in older women: sustained effect of an intervention to promote breast cancer awareness in routine clinical practice.

PubMed

Dodd, Rachael H; Forster, Alice S; Sellars, Sarah; Patnick, Julietta; Ramirez, Amanda J; Forbes, Lindsay J L

2017-06-05

Older women have poorer survival from breast cancer, which may be at least partly due to poor breast cancer awareness leading to delayed presentation and more advanced stage at diagnosis. In a randomised trial, an intervention to promote early presentation of breast cancer in older women increased breast cancer awareness at 1 year compared with usual care (24 versus 4%). We examined its effectiveness in routine clinical practice. We piloted the intervention delivered by practising health professionals to women aged about 70 in four breast screening services. We measured the effect on breast cancer awareness at 1 year compared with comparison services, where women did not receive the intervention. At 1 year, 25% of women in pilot services were breast cancer aware compared with 4% in comparison services (p = 0.001). The components of breast cancer awareness were knowledge of breast cancer non-lump symptoms (pilot: 63% vs comparison: 82% at 1 year; OR = 2.56, 95% CI 1.92-3.42), knowledge of age related risk (pilot: 8% vs comparison: 36% at 1 year; OR = 5.56, 95% CI 4.0-7.74) and reported breast checking (pilot: 70% vs comparison: 78% at 1 year; OR = 1.49, 95% CI 1.13-1.96). The intervention may be as effective in routine clinical practice as in a randomised controlled trial. This intervention has the potential to reduce patient delay in the diagnosis of breast cancer in older women. The PEP trial was registered with the International Standard Registered Clinical/soCial sTudy Number (ISRCTN) as a clinical trial ( ISRCTN31994827 ) on 3rd October 2007.

Cancer/stroma interplay via cyclooxygenase-2 and indoleamine 2,3-dioxygenase promotes breast cancer progression.

PubMed

Chen, Jing-Yi; Li, Chien-Feng; Kuo, Cheng-Chin; Tsai, Kelvin K; Hou, Ming-Feng; Hung, Wen-Chun

2014-07-25

Expression of indoleamine 2,3-dioxygenase (IDO) in primary breast cancer increases tumor growth and metastasis. However, the clinical significance of stromal IDO and the regulation of stromal IDO are unclear. Metabolomics and enzyme-linked immunosorbent assay (ELISA) were used to study the effect of cyclooxygenase-2 (COX-2)-overexpressing breast cancer cells on IDO expression in co-cultured human breast fibroblasts. Biochemical inhibitors and short-hairpin RNA (shRNA) were used to clarify how prostaglandin E2 (PGE2) upregulates IDO expression. Associations of stromal IDO with clinicopathologic parameters were tested in tumor specimens. An orthotopic animal model was used to examine the effect of COX-2 and IDO inhibitors on tumor growth. Kynurenine, the metabolite generated by IDO, increases in the supernatant of fibroblasts co-cultured with COX-2-overexpressing breast cancer cells. PGE2 released by cancer cells upregulates IDO expression in fibroblasts through an EP4/signal transducer and activator of transcription 3 (STAT3)-dependent pathway. Conversely, fibroblast-secreted kynurenine promotes the formation of the E-cadherin/Aryl hydrocarbon receptor (AhR)/S-phase kinase-associated protein 2 (Skp2) complex, resulting in degradation of E-cadherin to increase breast cancer invasiveness. The enhancement of motility of breast cancer cells induced by co-culture with fibroblasts is suppressed by the IDO inhibitor 1-methyl-tryptophan. Pathological analysis demonstrates that upregulation of stromal IDO is a poor prognosis factor and is associated with of COX-2 overexpression. Co-expression of cancer COX-2 and stromal IDO predicts a worse disease-free and metastasis-free survival. Finally, COX-2 and IDO inhibitors inhibit tumor growth in vivo. Integration of metabolomics and molecular and pathological approaches reveals the interplay between cancer and stroma via COX-2, and IDO promotes tumor progression and predicts poor patient survival.

A cluster of inflammatory breast cancer (IBC) in an office setting: additional evidence of the importance of environmental factors in IBC etiology.

PubMed

Duke, Tina J; Jahed, Nasreen C; Veneroso, Carmela C; Da Roza, Ricardo; Johnson, Owen; Hoffman, Daniel; Barsky, Sanford H; Levine, Paul H

2010-11-01

We investigated a cluster of three cases of inflammatory breast cancer (IBC) diagnosed within 10 months in an office setting of 24 people. Information about medical history, pregnancy history, family history of breast cancer, oral contraceptive use/hormone replacement therapy, exposure to possible oncogenic agents and tumor promoters were obtained to determine whether there were differences in risk factors for IBC between cases and controls. The physical environment and location of the cases' office raised concern about air and water quality as well as radiation as being contributory risk factors for developing IBC. Of the three women with IBC, two had high exposures to pesticides/herbicides, all three used oral contraceptives and two used hormone replacement therapy at the time of diagnosis, two had a family history of breast cancer, and two were obese. Among fifteen controls four had pesticide/herbicide exposure, one had a family history of breast cancer, nine used oral contraceptives, seven used hormone replacement therapy, and five were obese. No specific environmental causes were established for this cluster. Several promoting factors have been suggested that could result in subclinical breast cancer emerging as IBC. Among them are exogenous hormones and exposure to herbicides/pesticides.

Factors affecting exclusive breast-feeding during the first 6 months in Korea.

PubMed

Kim, Myo Jing; Kim, Yu-Mi; Yoo, Jae-Ho

2013-04-01

The aim of this study was to identify the status of exclusive breast-feeding (EBF) in Korea and analyze the factors affecting exclusive breast-feeding at 6 months of age. This study was based on data obtained from the Korea National Health and Nutrition Examination Survey (KNHANES) IV, conducted from January 2007 to December 2008. A total of 404 mother-infant pairs were recruited. Exclusive breast-feeding was defined according to the criteria established by the World Health Organization. The rate of EBF was 60.9% for 1 month, 55.0% for 3 months, 35.4% for 6 months, 3.7% for 9 months and 1.2% for 12 months after birth. According to a stepwise logistic regression analysis, factors that were positively associated with EBF at 6 months were younger maternal age (odds ratio [OR] = 0.85, 95% confidence interval [CI]: 0.79-0.92), higher maternal education level (OR = 2.29, 95%CI: 1.17-4.46) and living in a capital city (OR = 2.64, 95%CI: 1.46-4.75). The rate of EBF in Korea is still suboptimal. To promote EBF, persistent and systematic education and campaigns for breast-feeding should be provided, particularly in vulnerable regions. © 2012 The Authors. Pediatrics International © 2012 Japan Pediatric Society.

Stimulation of host bone marrow stromal cells by sympathetic nerves promotes breast cancer bone metastasis in mice.

PubMed

Campbell, J Preston; Karolak, Matthew R; Ma, Yun; Perrien, Daniel S; Masood-Campbell, S Kathryn; Penner, Niki L; Munoz, Steve A; Zijlstra, Andries; Yang, Xiangli; Sterling, Julie A; Elefteriou, Florent

2012-07-01

Bone and lung metastases are responsible for the majority of deaths in patients with breast cancer. Following treatment of the primary cancer, emotional and psychosocial factors within this population precipitate time to recurrence and death, however the underlying mechanism(s) remain unclear. Using a mouse model of bone metastasis, we provide experimental evidence that activation of the sympathetic nervous system, which is one of many pathophysiological consequences of severe stress and depression, promotes MDA-231 breast cancer cell colonization of bone via a neurohormonal effect on the host bone marrow stroma. We demonstrate that induction of RANKL expression in bone marrow osteoblasts, following β2AR stimulation, increases the migration of metastatic MDA-231 cells in vitro, independently of SDF1-CXCR4 signaling. We also show that the stimulatory effect of endogenous (chronic stress) or pharmacologic sympathetic activation on breast cancer bone metastasis in vivo can be blocked with the β-blocker propranolol, and by knockdown of RANK expression in MDA-231 cells. These findings indicate that RANKL promotes breast cancer cell metastasis to bone via its pro-migratory effect on breast cancer cells, independently of its effect on bone turnover. The emerging clinical implication, supported by recent epidemiological studies, is that βAR-blockers and drugs interfering with RANKL signaling, such as Denosumab, could increase patient survival if used as adjuvant therapy to inhibit both the early colonization of bone by metastatic breast cancer cells and the initiation of the "vicious cycle" of bone destruction induced by these cells.

Evaluation of aldehyde dehydrogenase 1 and transcription factors in both primary breast cancer and axillary lymph node metastases as a prognostic factor.

PubMed

Ito, Maiko; Shien, Tadahiko; Omori, Masako; Mizoo, Taeko; Iwamoto, Takayuki; Nogami, Tomohiro; Motoki, Takayuki; Taira, Naruto; Doihara, Hiroyoshi; Miyoshi, Shinichiro

2016-05-01

Aldehyde dehydrogenase 1 (ALDH1) is a marker of breast cancer stem cells, and the expression of ALDH1 may be a prognostic factor of poor clinical outcome. The epithelial-mesenchymal transition may produce cells with stem-cell-like properties promoted by transcription factors. We investigated the expression of ALDH1 and transcription factors in both primary and metastatic lesions, and prognostic value of them in breast cancer patients with axillary lymph node metastasis (ALNM). Forty-seven breast cancer patients with ALNM who underwent surgery at Okayama University Hospital from 2002 to 2008 were enrolled. We retrospectively evaluated the levels of ALDH1 and transcription factors, such as Snail, Slug and Twist, in both primary and metastatic lesions by immunohistochemistry. In primary lesions, the positive rate of ALDH1, Snail, Slug and Twist was 19, 49, 40 and 26%, respectively. In lymph nodes, that of ALDH1, Snail, Slug and Twist was 21, 32, 13 and 23%, respectively. The expression of ALDH1 or transcription factors alone was not significantly associated with a poor prognosis. However, co-expression of ALDH1 and Slug in primary lesions was associated with a shorter DFS (P = 0.009). The evaluation of the co-expression of ALDH1 and transcription factors in primary lesions may be useful in prognosis of node-positive breast cancers.

JAK2-binding long noncoding RNA promotes breast cancer brain metastasis

PubMed Central

Wang, Shouyu; Liang, Ke; Hu, Qingsong; Li, Ping; Song, Jian; Yang, Yuedong; Yao, Jun; Mangala, Lingegowda Selanere; Li, Chunlai; Park, Peter K.; Hawke, David H.; Zhou, Jianwei; Zhou, Yan; Xia, Weiya; Hung, Mien-Chie; Marks, Jeffrey R.; Gallick, Gary E.; Lopez-Berestein, Gabriel; Flores, Elsa R.; Sood, Anil K.; Huang, Suyun; Yu, Dihua; Yang, Liuqing

2017-01-01

Conventional therapies for breast cancer brain metastases (BCBMs) have been largely ineffective because of chemoresistance and impermeability of the blood-brain barrier. A comprehensive understanding of the underlying mechanism that allows breast cancer cells to infiltrate the brain is necessary to circumvent treatment resistance of BCBMs. Here, we determined that expression of a long noncoding RNA (lncRNA) that we have named lncRNA associated with BCBM (Lnc-BM) is prognostic of the progression of brain metastasis in breast cancer patients. In preclinical murine models, elevated Lnc-BM expression drove BCBM, while depletion of Lnc-BM with nanoparticle-encapsulated siRNAs effectively treated BCBM. Lnc-BM increased JAK2 kinase activity to mediate oncostatin M– and IL-6–triggered STAT3 phosphorylation. In breast cancer cells, Lnc-BM promoted STAT3-dependent expression of ICAM1 and CCL2, which mediated vascular co-option and recruitment of macrophages in the brain, respectively. Recruited macrophages in turn produced oncostatin M and IL-6, thereby further activating the Lnc-BM/JAK2/STAT3 pathway and enhancing BCBM. Collectively, our results show that Lnc-BM and JAK2 promote BCBMs by mediating communication between breast cancer cells and the brain microenvironment. Moreover, these results suggest targeting Lnc-BM as a potential strategy for fighting this difficult disease. PMID:29130936

Detection of 14-3-3 sigma (σ) promoter methylation as a noninvasive biomarker using blood samples for breast cancer diagnosis

PubMed Central

Ye, Meng; Huang, Tao; Ying, Ying; Li, Jinyun; Yang, Ping; Ni, Chao; Zhou, Chongchang; Chen, Si

2017-01-01

As a tumor suppressor gene, 14-3-3 σ has been reported to be frequently methylated in breast cancer. However, the clinical effect of 14-3-3 σ promoter methylation remains to be verified. This study was performed to assess the clinicopathological significance and diagnostic value of 14-3-3 σ promoter methylation in breast cancer. 14-3-3 σ promoter methylation was found to be notably higher in breast cancer than in benign lesions and normal breast tissue samples. We did not observe that 14-3-3 σ promoter methylation was linked to the age status, tumor grade, clinic stage, lymph node status, histological subtype, ER status, PR status, HER2 status, or overall survival of patients with breast cancer. The combined sensitivity, specificity, AUC (area under the curve), positive likelihood ratios (PLR), negative likelihood ratios (NLR), diagnostic odds ratio (DOR), and post-test probability values (if the pretest probability was 30%) of 14-3-3 σ promoter methylation in blood samples of breast cancer patients vs. healthy subjects were 0.69, 0.99, 0.86, 95, 0.31, 302, and 98%, respectively. Our findings suggest that 14-3-3 σ promoter methylation may be associated with the carcinogenesis of breast cancer and that the use of 14-3-3 σ promoter methylation might represent a useful blood-based biomarker for the clinical diagnosis of breast cancer. PMID:27999208

Do insulin-like growth factors mediate the effect of alcohol on breast cancer risk?

PubMed

Yu, H; Berkel, J

1999-06-01

Despite a large number of epidemiologic studies demonstrating an increased risk of breast cancer in association with alcohol consumption, a causal relationship between alcohol intake and breast cancer risk remains to be determined. Several biological mechanisms have been proposed, but none of them explains well the features of the association, i.e. a modest increase in risk, a limited range of dose-response relationship and no further increase in risk among heavy drinkers. A new mechanism underlying a possible biological role of alcohol in breast cancer is proposed in this paper. Moderate consumption of alcohol increases the production of insulin-like growth factors (IGFs) by the liver and elevated IGFs via circulation stimulate or promote the development and/or growth of breast cancer. The effect of alcohol on IGF production declines among heavy drinkers as alcohol-caused liver-function damage results in no further increase in IGF production. Therefore, compared to moderate drinkers, heavy alcohol users do not have a higher risk of breast cancer.

Yap1 promotes the survival and self-renewal of breast tumor initiating cells via inhibiting Smad3 signaling

PubMed Central

Sun, Jian-Guo; Chen, Xie-Wan; Zhang, Lu-Ping; Wang, Jiang; Diehn, Max

2016-01-01

Tumor initiating cells (TICs) serve as the root of tumor growth. After identifying TICs in spontaneous breast tumors of the MMTV-Wnt1 mouse model, we confirmed the specific expression and activation of Yes-associated protein 1 (Yap1) within TICs. To investigate the role of Yap1 in the self-renewal of breast TICs and the underlying mechanism, we sorted CD49fhighEpCAMlow cells as breast TICs. Active Yap1 with ectopic expression in breast TICs promoted their colony formation in vitro (p< 0.01) and self-renewal in vivo (p< 0.01), and led to a 4-fold increase in TIC frequency (p< 0.05). A conditional knock-out mouse was reconstructed to generate Yap1 knock-out breast tumors. The loss of Yap1 led to a dramatic growth disadvantage of breast TICs in vitro (p< 0.01) and in vivo (p< 0.01), and it also led to an over 200-fold decrease in TIC frequency (p< 0.01). The expression of active Yap1 was negatively correlated with that of phosphorylated Smad3 (p-Smad3). Transforming growth factor β (TGF-β) served as a strong enhancer of Smad3 and an inhibitor of clonogenesis of TICs. The presence of SIS3, a specific inhibitor of Smad3, could rescue the TGF-β -induced growth inhibition and reverse the Smad3 inhibition by Yap1. Analysis of a database containing 2,072 human breast cancer samples showed that higher expressions of Yap1 correlated with a poorer outcome of a 15-year survival rate and median overall survival (mOS)in patients, especially in those with basal breast tumors without estrogen receptor 1 (ER) expression. The findings indicate that active Yap1 promotes the self-renewal of breast TICs by inhibiting Smad3 signaling. PMID:26695440

Emodin Inhibits Breast Cancer Growth by Blocking the Tumor-Promoting Feedforward Loop between Cancer Cells and Macrophages.

PubMed

Iwanowycz, Stephen; Wang, Junfeng; Hodge, Johnie; Wang, Yuzhen; Yu, Fang; Fan, Daping

2016-08-01

Macrophage infiltration correlates with severity in many types of cancer. Tumor cells recruit macrophages and educate them to adopt an M2-like phenotype through the secretion of chemokines and growth factors, such as MCP1 and CSF1. Macrophages in turn promote tumor growth through supporting angiogenesis, suppressing antitumor immunity, modulating extracellular matrix remodeling, and promoting tumor cell migration. Thus, tumor cells and macrophages interact to create a feedforward loop supporting tumor growth and metastasis. In this study, we tested the ability of emodin, a Chinese herb-derived compound, to inhibit breast cancer growth in mice and examined the underlying mechanisms. Emodin was used to treat mice bearing EO771 or 4T1 breast tumors. It was shown that emodin attenuated tumor growth by inhibiting macrophage infiltration and M2-like polarization, accompanied by increased T-cell activation and reduced angiogenesis in tumors. The tumor inhibitory effects of emodin were lost in tumor-bearing mice with macrophage depletion. Emodin inhibited IRF4, STAT6, and C/EBPβ signaling and increased inhibitory histone H3 lysine 27 tri-methylation (H3K27m3) on the promoters of M2-related genes in tumor-associated macrophages. In addition, emodin inhibited tumor cell secretion of MCP1 and CSF1, as well as expression of surface anchoring molecule Thy-1, thus suppressing macrophage migration toward and adhesion to tumor cells. These results suggest that emodin acts on both breast cancer cells and macrophages and effectively blocks the tumor-promoting feedforward loop between the two cell types, thereby inhibiting breast cancer growth and metastasis. Mol Cancer Ther; 15(8); 1931-42. ©2016 AACR. ©2016 American Association for Cancer Research.

Estrogen and progesterone promote breast cancer cell proliferation by inducing cyclin G1 expression.

PubMed

Tian, J-M; Ran, B; Zhang, C-L; Yan, D-M; Li, X-H

2018-01-23

Breast cancer is the most common cause of cancer among women in most countries (WHO). Ovarian hormone disorder is thought to be associated with breast tumorigenesis. The present study investigated the effects of estrogen and progesterone administration on cell proliferation and underlying mechanisms in breast cancer MCF-7 cells. It was found that a single administration of estradiol (E2) or progesterone increased MCF-7 cell viability in a dose-dependent manner and promoted cell cycle progression by increasing the percentage of cells in the G2/M phase. A combination of E2 and progesterone led to a stronger effect than single treatment. Moreover, cyclin G1 was up-regulated by E2 and/or progesterone in MCF-7 cells. After knockdown of cyclin G1 in MCF-7 cells using a specific shRNA, estradiol- and progesterone-mediated cell viability and clonogenic ability were significantly limited. Additionally, estradiol- and progesterone-promoted cell accumulation in the G2/M phase was reversed after knockdown of cyclin G1. These data indicated that estrogen and progesterone promoted breast cancer cell proliferation by inducing the expression of cyclin G1. Our data indicated that novel therapeutics against cyclin G1 are promising for the treatment of estrogen- and progesterone-mediated breast cancer progression.

Risk factors for Staphylococcus aureus postpartum breast abscess.

PubMed

Branch-Elliman, Westyn; Golen, Toni H; Gold, Howard S; Yassa, David S; Baldini, Linda M; Wright, Sharon B

2012-01-01

Staphylococcus aureus (SA) breast abscesses are a complication of the postpartum period. Risk factors for postpartum SA breast abscesses are poorly defined, and literature is conflicting. Whether risk factors for methicillin-resistant SA (MRSA) and methicillin-susceptible SA (MSSA) infections differ is unknown. We describe novel risk factors associated with postpartum breast abscesses and the changing epidemiology of this infection. We conducted a cohort study with a nested case-control study (n = 216) involving all patients with culture-confirmed SA breast abscess among >30 000 deliveries at our academic tertiary care center from 2003 through 2010. Data were collected from hospital databases and through abstraction from medical records. All SA cases were compared with both nested controls and full cohort controls. A subanalysis was completed to determine whether risk factors for MSSA and MRSA breast abscess differ. Univariate analysis was completed using Student's t test, Wilcoxon rank-sum test, and analysis of variance, as appropriate. A multivariable stepwise logistic regression was used to determine final adjusted results for both the case-control and the cohort analyses. Fifty-four cases of culture-confirmed abscess were identified: 30 MRSA and 24 MSSA. Risk factors for postpartum SA breast abscess in multivariable analysis include in-hospital identification of a mother having difficulty breastfeeding (odds ratio, 5.00) and being a mother employed outside the home (odds ratio, 2.74). Risk factors did not differ between patients who developed MRSA and MSSA infections. MRSA is an increasingly important pathogen in postpartum women; risk factors for postpartum SA breast abscess have not changed with the advent of community-associated MRSA.

ENVIRONMENTAL FACTORS AFFECTING BREAST CANCER SUSCEPTIBILITY

EPA Science Inventory

Environmental Factors Affecting Breast Cancer Susceptibility
Suzanne. E. Fenton
US EPA, ORD, MD-67 NHEERL, Reproductive Toxicology Division, Research Triangle Park, NC 27711.

Breast cancer is still the most common malignancy afflicting women in the Western world. Alt...

Vasohibin 2 promotes epithelial-mesenchymal transition in human breast cancer via activation of transforming growth factor β 1 and hypoxia dependent repression of GATA-binding factor 3.

PubMed

Tu, Min; Li, Zhanjun; Liu, Xian; Lv, Nan; Xi, Chunhua; Lu, Zipeng; Wei, Jishu; Song, Guoxin; Chen, Jianmin; Guo, Feng; Jiang, Kuirong; Wang, Shui; Gao, Wentao; Miao, Yi

2017-03-01

Vasohibin 2 (VASH2) is identified as an angiogenic factor, and has been implicated in tumor angiogenesis, proliferation and epithelial-mesenchymal transition (EMT). To investigate the EMT role of VASH2 in breast cancer, we overexpressed or knocked down expression of VASH2 in human breast cancer cell lines. We observed that VASH2 induced EMT in vitro and in vivo. The transforming growth factor β1 (TGFβ1) pathway was activated by VASH2, and expression of a dominant negative TGFβ type II receptor could block VASH2-mediated EMT. In clinical breast cancer tissues VASH2 positively correlated with TGFβ1 expression, but negatively correlated with E-cadherin (a marker of EMT) expression. Under hypoxic conditions in vitro or in vivo, we found that down-regulation of estrogen receptor 1 (ESR1) in VASH2 overexpressing ESR1 positive cells suppressed E-cadherin. Correlation coefficient analysis indicated that VASH2 and ESR1 expression were negatively correlated in clinical human breast cancer tissues. Further study revealed that a transcription factor of ESR1, GATA-binding factor 3 (GATA3), was down-regulated by VASH2 under hypoxia or in vivo. These findings suggest that VASH2 drives breast cancer cells to undergo EMT by activation of the TGFβ1 pathway and hypoxia dependent repression GATA3-ESR1 pathway, leading to cancer metastasis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Breast-feeding and responses to infant vaccines: constitutional and environmental factors.

PubMed

Dórea, José G

2012-11-01

Neonates and nursing infants are special with regard to immune development and vulnerability to infectious diseases. Although breast-feeding is essential to modulate and prime immune defenses, vaccines (an interventional prophylaxis) are crucial to prevent and control infectious diseases. During nursing, the type of feeding influences infants' natural defenses (including gut colonization) and their response to vaccines, both through cell-mediated immunity and specific antibody production. Given the variety and combination of vaccine components (antigens and excipients, preservative thimerosal, and aluminum adjuvants) and route of administration, there is a need to examine the role of infant feeding practices in intended and nonintended outcomes of vaccination. Maternal factors related to milk constituents (nutrients and pollutants) and feeding practices can affect response to vaccines. Collectively, studies that compared type of feeding (or used breast-feeding-adjusted statistical models) showed significant influence on some vaccines taken during infancy. Nurslings deprived of the full benefit of breast-feeding could have altered immune responses affecting vaccine outcome. In the absence of studies elucidating neurodevelopment (including excitoxicity) and immunotoxicity issues, vaccination practices should promote and support breast-feeding. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

ATM kinase sustains breast cancer stem-like cells by promoting ATG4C expression and autophagy.

PubMed

Antonelli, Martina; Strappazzon, Flavie; Arisi, Ivan; Brandi, Rossella; D'Onofrio, Mara; Sambucci, Manolo; Manic, Gwenola; Vitale, Ilio; Barilà, Daniela; Stagni, Venturina

2017-03-28

The efficacy of Ataxia-Telangiectasia Mutated (ATM) kinase signalling inhibition in cancer therapy is tempered by the identification of new emerging functions of ATM, which suggests that the role of this protein in cancer progression is complex. We recently demonstrated that this tumor suppressor gene could act as tumor promoting factor in HER2 (Human Epidermal Growth Factor Receptor 2) positive breast cancer. Herein we put in evidence that ATM expression sustains the proportion of cells with a stem-like phenotype, measured as the capability to form mammospheres, independently of HER2 expression levels. Transcriptomic analyses revealed that, in mammospheres, ATM modulates the expression of cell cycle-, DNA repair- and autophagy-related genes. Among these, the silencing of the autophagic gene, autophagy related 4C cysteine peptidase (ATG4C), impairs mammosphere formation similarly to ATM depletion. Conversely, ATG4C ectopic expression in cells silenced for ATM expression, rescues mammospheres growth. Finally, tumor array analyses, performed using public data, identify a significant correlation between ATM and ATG4C expression levels in all human breast cancer subtypes, except for the basal-like one.Overall, we uncover a new connection between ATM kinase and autophagy regulation in breast cancer. We demonstrate that, in breast cancer cells, ATM and ATG4C are essential drivers of mammosphere formation, suggesting that their targeting may improve current approaches to eradicate breast cancer cells with a stem-like phenotype.

The Combined Association of Modifiable Risk Factors with Breast Cancer Risk in the Women's Health Initiative.

PubMed

Arthur, Rhonda; Wassertheil-Smoller, Sylvia; Manson, JoAnn E; Luo, Juhua; Snetselaar, Linda; Hastert, Theresa; Caan, Bette; Qi, Lihong; Rohan, Thomas

2018-06-01

Although several modifiable risk factors have been independently associated with risk of breast cancer, few studies have investigated their joint association with breast cancer risk. Using a healthy lifestyle index (HLI) score, we assessed the association of a combination of selected modifiable risk factors (diet, alcohol, physical activity, BMI, and smoking) with risk of invasive breast cancer in the Women's Health Initiative (WHI). This study comprised 131,833 postmenopausal women, of whom 8,168 had breast cancer, who were enrolled in the WHI Observational Study or the WHI clinical trials. Cox proportional hazards regression was used to estimate the HRs and 95% confidence intervals (CI) for the association of the score with the risk of developing breast cancer overall and according to specific breast cancer clinicopathologic characteristics. There was a 4% reduction in the risk of breast cancer per unit increase in the HLI score. Compared with those with an HLI score in the lowest quintile level, those in the highest quintile level had 30%, 37%, and 30% lower risk for overall, ER + /PR + , and HER2 + breast cancer, respectively (HR = 0.70; 95% CI, 0.64-0.76; 0.63, 0.57-0.69; and 0.70; 0.55-0.90, respectively). We also observed inverse associations between the score and risk of breast cancer irrespective of nodal status, tumor grade, and stage of the disease. Most individual lifestyle factors were independently associated with the risk of breast cancer. Our findings support the view that promoting healthy lifestyle practices may be beneficial with respect to lowering risk of breast cancer among postmenopausal women. Cancer Prev Res; 11(6); 317-26. ©2018 AACR See related editorial by Friedenreich and McTiernan, p. 313 . ©2018 American Association for Cancer Research.

A qualitative synthesis of trials promoting physical activity behaviour change among post-treatment breast cancer survivors.

PubMed

Short, Camille E; James, Erica L; Stacey, Fiona; Plotnikoff, Ronald C

2013-12-01

Health outcome trials have provided strong evidence that participating in regular physical activity can improve the quality of life and health of post-treatment breast cancer survivors. Focus is now needed on how to promote changes in physical activity behaviour among this group. This systematic review examines the efficacy of behavioural interventions for promoting physical activity among post-treatment breast cancer survivors. Behavioural intervention studies published up until July 2012 were identified through a systematic search of two databases: MEDLINE and CINAHL, and by searching reference lists of relevant publications and scanning citation libraries of project staff. Eight out of the ten identified studies reported positive intervention effects on aerobic physical activity behaviour, ranging from during the intervention period to 6 months post-intervention. Only two studies reported intervention effect sizes. The identification of factors related to efficacy was not possible because of the limited number and heterogeneity of studies included, as well as the lack of effect sizes reported. Nonetheless, an examination of the eight studies that did yield significant intervention effects suggests that 12-week interventions employing behaviour change techniques (e.g., self-monitoring and goal setting) derived from a variety of theories and delivered in a variety of settings (i.e., one-on-one, group or home) can be effective at changing the aerobic physical activity behaviour of breast cancer survivors in the mid- to long terms. Behavioural interventions do hold promise for effectively changing physical activity behaviour among breast cancer survivors. However, future research is needed to address the lack of studies exploring long-term intervention effects, mediators of intervention effects and interventions promoting resistance-training activity, and to address issues impacting on validity, such as the limited use of objective physical activity measures and

PTP1B promotes aggressiveness of breast cancer cells by regulating PTEN but not EMT.

PubMed

Liu, Xue; Chen, Qian; Hu, Xu-Gang; Zhang, Xian-Chao; Fu, Ti-Wei; Liu, Qing; Liang, Yan; Zhao, Xi-Long; Zhang, Xia; Ping, Yi-Fang; Bian, Xiu-Wu

2016-10-01

Metastasis is a complicated, multistep process and remains the major cause of cancer-related mortality. Exploring the molecular mechanisms underlying tumor metastasis is crucial for development of new strategies for cancer prevention and treatment. In this study, we found that protein tyrosine phosphatase 1B (PTP1B) promoted breast cancer metastasis by regulating phosphatase and tensin homolog (PTEN) but not epithelial-mesenchymal transition (EMT). By detecting PTP1B expression of the specimens from 128 breast cancer cases, we found that the level of PTP1B was higher in breast cancer tissues than the corresponding adjacent normal tissues. Notably, PTP1B was positively associated with lymph node metastasis (LNM) and estrogen receptor (ER) status. In vitro, disturbing PTP1B expression obviously attenuated cell migration and invasion. On the contrary, PTP1B overexpression significantly increased migration and invasion of breast cancer cells. Mechanistically, PTP1B knockdown upregulated PTEN, accompanied with an abatement of AKT phosphorylation and the expression of matrix metalloproteinase 2 (MMP2) and MMP7. Conversely, forced expression of PTP1B reduced PTEN and increased AKT phosphorylation as well as the expression of MMP2 and MMP7. Notably, neither EMT nor stemness of breast cancer cells was regulated by PTP1B. We also found that PTP1B acted as an independent prognostic factor and predicted poor prognosis in ER-positive breast cancer patients. Taken together, our findings provide advantageous evidence for the development of PTP1B as a potential therapeutic target for breast cancer, especially for ER-positive breast cancer patients.

Mammographic breast density as a risk factor for breast cancer: awareness in a recently screened clinical sample.

PubMed

O'Neill, Suzanne C; Leventhal, Kara Grace; Scarles, Marie; Evans, Chalanda N; Makariou, Erini; Pien, Edward; Willey, Shawna

2014-01-01

Breast density is an established, independent risk factor for breast cancer. Despite this, density has not been included in standard risk models or routinely disclosed to patients. However, this is changing in the face of legal mandates and advocacy efforts. Little information exists regarding women's awareness of density as a risk factor, their personal risk, and risk management options. We assessed awareness of density as a risk factor and whether sociodemographic variables, breast cancer risk factors. and perceived breast cancer risk were associated with awareness in 344 women with a recent screening mammogram at a tertiary care center. Overall, 62% of women had heard about density as a risk factor and 33% had spoken to a provider about breast density. Of the sample, 18% reported that their provider indicated that they had high breast density. Awareness of density as a risk factor was greater among White women and those with other breast cancer risk factors. Our results suggest that although a growing number of women are aware of breast density as a risk factor, this awareness varies. Growing mandates for disclosure suggest the need for patient education interventions for women at increased risk for the disease and to ensure all women are equally aware of their risks. Copyright © 2014 Jacobs Institute of Women's Health. Published by Elsevier Inc. All rights reserved.

Ethnicity-related variation in breast cancer risk factors.

PubMed

Bernstein, Leslie; Teal, Cayla R; Joslyn, Sue; Wilson, Jerome

2003-01-01

A variety of factors are predictors of breast cancer risk. However, the studies conducted to establish these risk factors have rarely included African American women. The few studies with sufficient numbers of African-American women suggest that risk factors for breast cancer among African-American women are similar to those of white women. Although risk factors may be similar for African-American and white women, differences in the prevalence of risk factors may explain the differences in patterns of incidence. The authors reviewed the epidemiologic studies of breast cancer among African-American women and identified resources with information regarding the prevalence of risk factors among African American and white women. Considerable variation exists in the studies of breast cancer risk factors among African American women. Because few studies have included sufficient numbers of African-American women, no firm conclusions can be drawn regarding whether risk estimates for African American women differ from those of white women. Estimates of the prevalence of breast cancer risk factors indicate that African American and white women differ in terms of their ages at menarche, menstrual cycle patterns, birth rates, lactation histories, patterns of oral contraceptive use, levels of obesity, frequency of menopausal hormone use, physical activity patterns, and alcohol intake. The risk factor profile of African-American women appears to differ from that of white women. This may explain in part, the higher incidence rates for African Americans before age 45 years and the lower incidence rates at older ages. Discussions of these data at a workshop highlighted the need for future research on breast cancer risk among African Americans. This research should acknowledge the heterogeneous heritage, cultural beliefs, and cultural knowledge of African-American women. Studies conducted in collaboration with the African-American community of women and with the breast cancer

Heregulin/ErbB3 Signaling Enhances CXCR4-Driven Rac1 Activation and Breast Cancer Cell Motility via Hypoxia-Inducible Factor 1α

PubMed Central

Lopez-Haber, Cynthia; Barrio-Real, Laura; Casado-Medrano, Victoria

2016-01-01

The growth factor heregulin (HRG), a ligand of ErbB3 and ErbB4 receptors, contributes to breast cancer development and the promotion of metastatic disease, and its expression in breast tumors has been associated with poor clinical outcome and resistance to therapy. In this study, we found that breast cancer cells exposed to sustained HRG treatment show markedly enhanced Rac1 activation and migratory activity in response to the CXCR4 ligand SDF-1/CXCL12, effects mediated by P-Rex1, a Rac-guanine nucleotide exchange factor (GEF) aberrantly expressed in breast cancer. Notably, HRG treatment upregulates surface expression levels of CXCR4, a G protein-coupled receptor (GPCR) implicated in breast cancer metastasis and an indicator of poor prognosis in breast cancer patients. A detailed mechanistic analysis revealed that CXCR4 upregulation and sensitization of the Rac response/motility by HRG are mediated by the transcription factor hypoxia-inducible factor 1α (HIF-1α) via ErbB3 and independently of ErbB4. HRG caused prominent induction in the nuclear expression of HIF-1α, which transcriptionally activates the CXCR4 gene via binding to a responsive element located in positions −1376 to −1372 in the CXCR4 promoter, as revealed by mutagenesis analysis and chromatin immunoprecipitation (ChIP). Our results uncovered a novel function for ErbB3 in enhancing breast cancer cell motility and sensitization of the P-Rex1/Rac1 pathway through HIF-1α-mediated transcriptional induction of CXCR4. PMID:27185877

Identification of the Downstream Promoter Targets of Smad Tumor Suppressors in Human Breast Cancer Cells

DTIC Science & Technology

2004-10-01

signaling mediator Smad2, Smad3 and Smad4 which form oligomeric complexes and migrate into nucleus to function as transcription factors to modulate... Smad3 and Smad4. 2. Identification of the downstream promoter targets of Smad3 or Smad4 in breast cancer cells. 3. Identify Smad4 regulated downstream...Development of a novel chromatin immunoprecipitation assay (CHIPS) using a TAP-TAG system to isolate in vivo binding targets of Smad3 and Smad4

Promoting Breast Cancer Screening through Storytelling by Chamorro Cancer Survivors

PubMed Central

Manglona, Rosa Duenas; Robert, Suzanne; Isaacson, Lucy San Nicolas; Garrido, Marie; Henrich, Faye Babauta; Santos, Lola Sablan; Le, Daisy; Peters, Ruth

2017-01-01

The largest Chamorro population outside of Guam and the Mariana Islands reside in California. Cancer health disparities disproportionally affect Pacific Islander communities, including the Chamorro, and breast cancer is the most common cancer affecting women. To address health concerns such as cancer, Pacific Islander women frequently utilize storytelling to initiate conversations about health and to address sensitive topics such as breast health and cancer. One form of storytelling used in San Diego is a play that conveys the message of breast cancer screening to the community in a culturally and linguistically appropriate way. This play, Nan Nena’s Mammogram, tells the story of an older woman in the community who learns about breast cancer screening from her young niece. The story builds upon the underpinnings of Chamorro culture - family, community, support, and humor - to portray discussing breast health, getting support for breast screening, and visiting the doctor. The story of Nan Nena’s Mammogram reflects the willingness of a few pioneering Chamorro women to use their personal experiences of cancer survivorship to promote screening for others. Through the support of a Chamorro community-based organization, these Chamorro breast cancer survivors have used the success of Nan Nena’s Mammogram to expand their education activities and to form a new cancer survivor organization for Chamorro women in San Diego. PMID:29805328

Common breast cancer susceptibility loci are associated with triple negative breast cancer

PubMed Central

Stevens, Kristen N.; Vachon, Celine M.; Lee, Adam M.; Slager, Susan; Lesnick, Timothy; Olswold, Curtis; Fasching, Peter A.; Miron, Penelope; Eccles, Diana; Carpenter, Jane E.; Godwin, Andrew K.; Ambrosone, Christine; Winqvist, Robert; Schmidt, Marjanka K.; Cox, Angela; Cross, Simon S.; Sawyer, Elinor; Hartmann, Arndt; Beckmann, Matthias W.; Schulz-Wendtland, Rüdiger; Ekici, Arif B.; Tapper, William J; Gerty, Susan M; Durcan, Lorraine; Graham, Nikki; Hein, Rebecca; Nickels, Stephan; Flesch-Janys, Dieter; Heinz, Judith; Sinn, Hans-Peter; Konstantopoulou, Irene; Fostira, Florentia; Pectasides, Dimitrios; Dimopoulos, Athanasios M.; Fountzilas, George; Clarke, Christine L.; Balleine, Rosemary; Olson, Janet E.; Fredericksen, Zachary; Diasio, Robert B.; Pathak, Harsh; Ross, Eric; Weaver, JoEllen; Rüdiger, Thomas; Försti, Asta; Dünnebier, Thomas; Ademuyiwa, Foluso; Kulkarni, Swati; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Ko, Yon-Dschun; Van Limbergen, Erik; Janssen, Hilde; Peto, Julian; Fletcher, Olivia; Giles, Graham G.; Baglietto, Laura; Verhoef, Senno; Tomlinson, Ian; Kosma, Veli-Matti; Beesley, Jonathan; Greco, Dario; Blomqvist, Carl; Irwanto, Astrid; Liu, Jianjun; Blows, Fiona M.; Dawson, Sarah-Jane; Margolin, Sara; Mannermaa, Arto; Martin, Nicholas G.; Montgomery, Grant W; Lambrechts, Diether; dos Santos Silva, Isabel; Severi, Gianluca; Hamann, Ute; Pharoah, Paul; Easton, Douglas F.; Chang-Claude, Jenny; Yannoukakos, Drakoulis; Nevanlinna, Heli; Wang, Xianshu; Couch, Fergus J.

2012-01-01

Triple negative breast cancers are an aggressive subtype of breast cancer with poor survival, but there remains little known about the etiological factors which promote its initiation and development. Commonly inherited breast cancer risk factors identified through genome wide association studies (GWAS) display heterogeneity of effect among breast cancer subtypes as defined by estrogen receptor (ER) and progesterone receptor (PR) status. In the Triple Negative Breast Cancer Consortium (TNBCC), 22 common breast cancer susceptibility variants were investigated in 2,980 Caucasian women with triple negative breast cancer and 4,978 healthy controls. We identified six single nucleotide polymorphisms (SNPs) significantly associated with risk of triple negative breast cancer, including rs2046210 (ESR1), rs12662670 (ESR1), rs3803662 (TOX3), rs999737 (RAD51L1), rs8170 (19p13.11) and rs8100241 (19p13.11). Together, our results provide convincing evidence of genetic susceptibility for triple negative breast cancer. PMID:21844186

[Effects of an Individual Breast-feeding Promotion Program for Married Immigrant Women].

PubMed

Park, Mi Kyoung; Moon, So Hyun

2016-02-01

This study was designed to evaluate the effects of an individual breast-feeding promotion program to address breast-feeding knowledge, attitude, method and rate of practice for married immigrant women. A non-equivalent control group quasi-experimental design was used (experimental group=16, control group=17). The intervention consisted of 3 phases: (1) Within 2 hours of delivery - individual breast-feeding training through video/verbal/practical training education and demonstration (2) After 1~2 days - group training using video, model doll, and breast models (3) After 7 days - family visit, counseling, retraining and reinforcement training. The data were analyzed using non-parametric tests with the SPSS program. Married immigrant women who participated in the individual breast-feeding program scored high in knowledge, attitude, method and rate of practice compared to the control group. The results indicate that the individual breast-feeding program is very effective in increasing breast-feeding knowledge, attitude, method and rate of practicing breast feeding for married immigrant women. So, nurses are encouraged to aggressively utilize individual breast-feeding programs to help married immigrant women, who are exposed to vulnerability due to various situations.

Posttraumatic growth and associated socio-demographic and clinical factors in Chinese breast cancer survivors.

PubMed

Wang, Mu-Lan; Liu, Jun-E; Wang, Hui-Ying; Chen, Jing; Li, Yi-Ying

2014-10-01

The factors that affect posttraumatic growth (PTG) in breast cancer survivors have been discussed for many years, but it remains unclear which are most influential. The purpose of this study was to determine the level of PTG and identify associated socio-demographic and clinical factors in Chinese breast cancer survivors. A descriptive research design with a convenience sampling method was employed to collect data using the simplified Chinese version of the Posttraumatic Growth Inventory (PTGI-SC). This questionnaire was administered to 1227 participants recruited from eight tertiary hospitals and cancer survivor groups in Beijing between April 2010 and April 2012. PTG is present in Chinese breast cancer survivors, with an average PTGI-SC score of 70.18 ± 15.85. There were five variables in the regression model: exercise, other chronic disease, income, education level, and work status. Exercise showed the strongest positive association with PTG after breast cancer. Household income and educational level also positively influenced PTG. Survivors with other accompanying chronic diseases had lower PTG. Retired survivors had the highest PTG, those working had moderate PTG, and those on sick leave had the lowest PTG. PTG is common among Chinese breast cancer survivors. It is positively associated with exercise, income, education, and retirement, and negatively associated with the presence of other chronic diseases and working. The results may provide information on how to promote the development of PTG while nursing breast cancer survivors. Copyright © 2014 Elsevier Ltd. All rights reserved.

The controversial role of forkhead box F2 (FOXF2) transcription factor in breast cancer.

PubMed

Lo, Pang-Kuo

2017-01-01

Deregulating the subcellular localization, functions and expression of Forkhead box (FOX) transcription factors that are critically involved in embryonic development and multiple biological processes is known to result in the development and progression of diseases, in particular cancer. Human FOXF transcription factors, including FOXF1 and FOXF2, are a subfamily of the FOX gene family. The recent findings from ours and others have linked FOXF2 to breast cancer development and progression. Our studies have shown that FOXF2 acts as a tumor-suppressive inhibitor of DNA replication in luminal and HER2-positive breast cancers and as an oncogenic activator of the epithelial-mesenchymal transition (EMT) in triple-negative/basal-like breast cancers (TN/BLBC), suggesting that FOXF2 plays a dual role in breast cancer. However, studies from Feng's research group have pointed out an opposite role of FOXF2 in TN/BLBC, which acts as an inhibitor of the EMT and as a promoter of cell proliferation in TN/BLBC. These discrepancies between our and Feng's studies have caused controversy in the role of FOXF2 in breast cancer. This article reviews both studies and discusses what causes might have led to these inconsistencies as well as what future experiments are needed to solve this debate.

Fibroblast growth factor 8 is expressed at higher levels in lactating human breast and in breast cancer.

PubMed

Zammit, C; Coope, R; Gomm, J J; Shousha, S; Johnston, C L; Coombes, R C

2002-04-08

Fibroblast growth factor 8 can transform NIH3T3 cells and its expression has been found to be associated with breast and prostate cancer. Following our finding that fibroblast growth factor 8 mRNA expression is increased in breast cancer, we have undertaken an immunohistochemistry study of fibroblast growth factor 8 expression in a series of human breast tissues and other normal tissues. Our findings confirm increased expression of fibroblast growth factor 8 in malignant breast tissue but also show significant fibroblast growth factor 8 expression in non-malignant breast epithelial cells. No significant difference in fibroblast growth factor 8 expression was found between different grades of ductal carcinoma, lobular carcinoma and ductal carcinoma in-situ or cancer of different oestrogen receptor, progesterone receptor or nodal status. The highest levels of fibroblast growth factor 8 expression were found in lactating breast tissues and fibroblast growth factor 8 was also detected in human milk. A survey of other normal tissues showed that fibroblast growth factor 8 is expressed in the proliferative cells of the dermis and epithelial cells in colon, ovary fallopian tube and uterus. Fibroblast growth factor 8 appears to be expressed in several organs in man and appears to have an importance in lactation.

Eukaryotic Translation Initiation Factor 4E Is a Feed-Forward Translational Coactivator of Transforming Growth Factor β Early Protransforming Events in Breast Epithelial Cells

PubMed Central

Decarlo, Lindsey; Mestel, Celine; Barcellos-Hoff, Mary-Helen

2015-01-01

Eukaryotic translation initiation factor 4E (eIF4E) is overexpressed early in breast cancers in association with disease progression and reduced survival. Much remains to be understood regarding the role of eIF4E in human cancer. We determined, using immortalized human breast epithelial cells, that elevated expression of eIF4E translationally activates the transforming growth factor β (TGF-β) pathway, promoting cell invasion, a loss of cell polarity, increased cell survival, and other hallmarks of early neoplasia. Overexpression of eIF4E is shown to facilitate the selective translation of integrin β1 mRNA, which drives the translationally controlled assembly of a TGF-β receptor signaling complex containing α3β1 integrins, β-catenin, TGF-β receptor I, E-cadherin, and phosphorylated Smad2/3. This receptor complex acutely sensitizes nonmalignant breast epithelial cells to activation by typically substimulatory levels of activated TGF-β. TGF-β can promote cellular differentiation or invasion and transformation. As a translational coactivator of TGF-β, eIF4E confers selective mRNA translation, reprogramming nonmalignant cells to an invasive phenotype by reducing the set point for stimulation by activated TGF-β. Overexpression of eIF4E may be a proinvasive facilitator of TGF-β activity. PMID:25986608

Suppression of breast cancer metastasis through the inactivation of ADP-ribosylation factor 1.

PubMed

Xie, Xiayang; Tang, Shou-Ching; Cai, Yafei; Pi, Wenhu; Deng, Libin; Wu, Guangyu; Chavanieu, Alain; Teng, Yong

2016-09-06

Metastasis is the major cause of cancer-related death in breast cancer patients, which is controlled by specific sets of genes. Targeting these genes may provide a means to delay cancer progression and allow local treatment to be more effective. We report for the first time that ADP-ribosylation factor 1 (ARF1) is the most amplified gene in ARF gene family in breast cancer, and high-level amplification of ARF1 is associated with increased mRNA expression and poor outcomes of patients with breast cancer. Knockdown of ARF1 leads to significant suppression of migration and invasion in breast cancer cells. Using the orthotopic xenograft model in NSG mice, we demonstrate that loss of ARF1 expression in breast cancer cells inhibits pulmonary metastasis. The zebrafish-metastasis model confirms that the ARF1 gene depletion suppresses breast cancer cells to metastatic disseminate throughout fish body, indicating that ARF1 is a very compelling target to limit metastasis. ARF1 function largely dependents on its activation and LM11, a cell-active inhibitor that specifically inhibits ARF1 activation through targeting the ARF1-GDP/ARNO complex at the Golgi, significantly impairs metastatic capability of breast cancer cell in zebrafish. These findings underline the importance of ARF1 in promoting metastasis and suggest that LM11 that inhibits ARF1 activation may represent a potential therapeutic approach to prevent or treat breast cancer metastasis.

FLT1 signaling in metastasis-associated macrophages activates an inflammatory signature that promotes breast cancer metastasis

PubMed Central

Zhang, Hui; Li, Jiufeng; He, Tianfang; Yeo, Eun-Jin; Soong, Daniel Y.H.; Carragher, Neil O.; Munro, Alison; Chang, Alvin; Bresnick, Anne R.; Lang, Richard A.

2015-01-01

Although the link between inflammation and cancer initiation is well established, its role in metastatic diseases, the primary cause of cancer deaths, has been poorly explored. Our previous studies identified a population of metastasis-associated macrophages (MAMs) recruited to the lung that promote tumor cell seeding and growth. Here we show that FMS-like tyrosine kinase 1 (Flt1, also known as VEGFR1) labels a subset of macrophages in human breast cancers that are significantly enriched in metastatic sites. In mouse models of breast cancer pulmonary metastasis, MAMs uniquely express FLT1. Using several genetic models, we show that macrophage FLT1 signaling is critical for metastasis. FLT1 inhibition does not affect MAM recruitment to metastatic lesions but regulates a set of inflammatory response genes, including colony-stimulating factor 1 (CSF1), a central regulator of macrophage biology. Using a gain-of-function approach, we show that CSF1-mediated autocrine signaling in MAMs is downstream of FLT1 and can restore the tumor-promoting activity of FLT1-inhibited MAMs. Thus, CSF1 is epistatic to FLT1, establishing a link between FLT1 and inflammatory responses within breast tumor metastases. Importantly, FLT1 inhibition reduces tumor metastatic efficiency even after initial seeding, suggesting that these pathways represent therapeutic targets in metastatic disease. PMID:26261265

Mint3 in bone marrow-derived cells promotes lung metastasis in breast cancer model mice.

PubMed

Hara, Toshiro; Murakami, Yoshinori; Seiki, Motoharu; Sakamoto, Takeharu

2017-08-26

Breast cancer is one of the most common cancers in women in the world. Although breast cancer is well treatable at the early stage, patients with distant metastases show a poor prognosis. Data from recent studies using transplantation models indicate that Mint3/APBA3 might promote breast cancer malignancy. However, whether Mint3 indeed contributes to tumor development, progression, or metastasis in vivo remains unclear. To address this, here we examined whether Mint3 depletion affects tumor malignancy in MMTV-PyMT breast cancer model mice. In MMTV-PyMT mice, Mint3 depletion did not affect tumor onset and tumor growth, but attenuated lung metastases. Experimental lung metastasis of breast cancer Met-1 cells derived from MMTV-PyMT mice also decreased in Mint3-depleted mice, indicating that host Mint3 expression affected lung metastasis of MMTV-PyMT-derived breast cancer cells. Further bone marrow transplant experiments revealed that Mint3 in bone marrow-derived cells promoted lung metastasis in MMTV-PyMT mice. Thus, targeting Mint3 in bone marrow-derived cells might be a good strategy for preventing metastasis and improving the prognosis of breast cancer patients. Copyright © 2017 Elsevier Inc. All rights reserved.

Ubiquitin-conjugating enzyme complex Uev1A-Ubc13 promotes breast cancer metastasis through nuclear factor-кB mediated matrix metalloproteinase-1 gene regulation

PubMed Central

2014-01-01

Introduction UEV1A encodes a ubiquitin-conjugating enzyme variant (Ubc13), which is required for Ubc13-catalyzed Lys63-linked polyubiquitination of target proteins and nuclear factor κB (NF-кB) activation. Previous reports have correlated the level of UEV1A expression with tumorigenesis; however, the detailed molecular events leading to tumors particularly breast cancer and metastasis are unclear. This study is to investigate roles of different UEV1 splicing variants, and its close homolog MMS2, in promoting tumorigenesis and metastasis in breast cancer cells. Methods We experimentally manipulated the UEV1 and MMS2 levels in MDA-MB-231 breast cancer cells and monitored their effects on cell invasion and migration, as well as tumor formation and metastasis in xenograft mice. The underlying molecular mechanisms leading to metastasis were also examined. Results It was found that overexpression of UEV1A alone, but not UEV1C or MMS2, is sufficient to induce cell invasion in vitro and metastasis in vivo. This process is mediated by NF-κB activation and requires functional Ubc13. Our experimental data establish that among NF-κB target genes, UEV1A-regulated matrix metalloproteinase-1 (MMP1) expression plays a critical role in cell invasion and metastasis. Interestingly, experimental depletion of UEV1 in MDA-MB-231 cells reduces MMP1 expression and prevents tumor formation and metastasis in a xenograft mouse model, while overexpression of MMP1 overrides the metastasis effects in UEV1-depleted cells. Conclusions These results identify UEV1A as a potential therapeutic target in the treatment of metastasic breast cancers. PMID:25022892

Clinicopathological significance of plasminogen activator inhibitor-1 promoter 4G/5G polymorphism in breast cancer: a meta-analysis.

PubMed

Lee, Ju-Han; Kim, Younghye; Choi, Jung-Woo; Kim, Young-Sik

2013-01-01

Plasminogen activator inhibitor type 1 (PAI-1) is associated with poor prognosis in breast cancer. Transcriptional expression of the PAI-1 can be controlled by PAI-1 promoter 4G/5G polymorphism. However, the significance of PAI-1 promoter 4G/5G polymorphism in breast cancer patients is contentious. To address this controversy, we conducted a meta-analysis for the relationships between PAI-1 promoter polymorphism and clinicopathological characteristics of breast cancer. Relevant published studies were identified using a search of PubMed, Embase, and the ISI Web of Science. The effect sizes of PAI-1 promoter 4G/5G polymorphism on breast cancer risk, lymph node metastasis, histologic grade, and overall survival were calculated by odds ratio (OR) or hazard ratio. The effect sizes were combined using a random-effects model. Individuals with 4G/4G genotype had a higher risk of breast cancer than those with the combined 4G/5G and 5G/5G genotypes (OR = 1.388; p = 0.031). Breast cancer patients with the 5G/5G genotype displayed lymph node metastasis more than patients with either the combined other genotypes (OR = 1.495; p = 0.027) or with the 4G/4G genotype (OR = 1.623; p = 0.018). However, the PAI-1 promoter 4G/5G polymorphism was not associated with histological grade or overall survival. PAI-1 promoter 4G/5G polymorphism is associated with a relatively increased risk of breast cancer development and lymph node metastasis. Copyright © 2013 IMSS. Published by Elsevier Inc. All rights reserved.

Protection, promotion and support of breast-feeding in Europe: current situation.

PubMed

Cattaneo, Adriano; Yngve, Agneta; Koletzko, Berthold; Guzman, Luis Ruiz

2005-02-01

To describe the current situation regarding protection, promotion and support of breast-feeding in Europe, as a first step towards the development of a blueprint for action. A questionnaire was completed by 29 key informants and 128 other informants in the EU, including member states, accession and candidate countries. EU countries do not fully comply with the policies and recommendations of the Global Strategy on Infant and Young Child Feeding that they endorsed during the 55th World Health Assembly in 2002. Some countries do not even comply with the targets of the Innocenti Declaration (1990). Pre-service training on breast-feeding practice is inadequate and in-service training achieves only low to medium coverage. The Baby Friendly Hospital Initiative is well developed only in three countries; in 19 countries, less than 15% of births occur in baby-friendly hospitals. The International Code of Marketing of Breastmilk Substitutes, endorsed in 1981 by all countries, is not fully applied and submitted to independent monitoring. The legislation for working mothers meets on average the International Labour Organization standards, but covers only women with full formal employment. Voluntary mother-to-mother support groups and trained peer counsellors are present in 27 and 13 countries, respectively. Breast-feeding rates span over a wide range; comparisons are difficult due to use of non-standard methods. The rate of exclusive breast-feeding at 6 months is low everywhere, even in countries with high initiation rates. EU countries need to revise their policies and practices to meet the principles inscribed in the Global Strategy on Infant and Young Child Feeding in order to better protect, promote and support breast-feeding.

CGI-99 promotes breast cancer metastasis via autocrine interleukin-6 signaling.

PubMed

Lin, C; Liao, W; Jian, Y; Peng, Y; Zhang, X; Ye, L; Cui, Y; Wang, B; Wu, X; Xiong, Z; Wu, S; Li, J; Wang, X; Song, L

2017-06-29

Metastatic relapse remains largely incurable and a major challenge of clinical management in breast cancer, but the underlying mechanisms are poorly understood. Herein, we report that CGI-99 is overexpressed in breast cancer tissues from patients with metastatic recurrence within 5 years. High CGI-99 significantly predicts poorer 5-year metastasis-free patient survival. We find that CGI-99 increases breast cancer stem cell properties, and potentiates efficient tumor lung colonization and outgrowth in vivo. Furthermore, we demonstrate that CGI-99 activates the autocrine interleukin-6 (IL-6)/STAT3 signaling by increasing the accumulation and activity of RNA polymerase II and p300 cofactor at the proximal promoter of IL-6. Importantly, delivery of the IL-6-receptor humanized monoclonal antibody tocilizumab robustly abrogates CGI-99-induced metastasis in vivo. Finally, we find that high levels of CGI-99 are significantly correlated with STAT3 hyperactivation in breast cancer patients. These findings reveal a potential mechanism for constitutive activation of autocrine IL-6/STAT3 signaling and may suggest a novel target for clinical intervention in breast cancer.

Surface Expression of TGFβ Docking Receptor GARP Promotes Oncogenesis and Immune Tolerance in Breast Cancer.

PubMed

Metelli, Alessandra; Wu, Bill X; Fugle, Caroline W; Rachidi, Saleh; Sun, Shaoli; Zhang, Yongliang; Wu, Jennifer; Tomlinson, Stephen; Howe, Philip H; Yang, Yi; Garrett-Mayer, Elizabeth; Liu, Bei; Li, Zihai

2016-12-15

GARP encoded by the Lrrc32 gene is the cell surface docking receptor for latent TGFβ, which is expressed naturally by platelets and regulatory T cells (Treg). Although Lrrc32 is amplified frequently in breast cancer, the expression and relevant functions of GARP in cancer have not been explored. Here, we report that GARP exerts oncogenic effects, promoting immune tolerance by enriching and activating latent TGFβ in the tumor microenvironment. We found that human breast, lung, and colon cancers expressed GARP aberrantly. In genetic studies in normal mammary gland epithelial and carcinoma cells, GARP expression increased TGFβ bioactivity and promoted malignant transformation in immunodeficient mice. In breast carcinoma-bearing mice that were immunocompetent, GARP overexpression promoted Foxp3 + Treg activity, which in turn contributed to enhancing cancer progression and metastasis. Notably, administration of a GARP-specific mAb limited metastasis in an orthotopic model of human breast cancer. Overall, these results define the oncogenic effects of the GARP-TGFβ axis in the tumor microenvironment and suggest mechanisms that might be exploited for diagnostic and therapeutic purposes. Cancer Res; 76(24); 7106-17. ©2016 AACR. ©2016 American Association for Cancer Research.

Factors influencing initiation and duration of breast feeding in Ireland.

PubMed

Leahy-Warren, Patricia; Mulcahy, Helen; Phelan, Agnes; Corcoran, Paul

2014-03-01

The aim of this research was to identify factors associated with mothers breast feeding and to identify, for those who breast fed, factors associated with breast feeding for as long as planned. breast feeding rates in Ireland are amongst the lowest in Europe. Research evidence indicates that in order for mothers to be successful at breast feeding, multiplicities of supports are necessary for both initiation and duration. The nature of these supports in tandem with other influencing factors requires analysis from an Irish perspective. cross-sectional study involving public health nurses and mothers in Ireland. This paper presents the results of the mothers' evaluation. mothers (n=1715) with children less than three years were offered a choice of completing the self-report questionnaires online or by mail. Data were analysed and reported using descriptive and inferential statistics. four in every five participants breast fed their infant and two thirds of them breast fed as long as planned. The multivariate logistic regression analysis identified that third level education, being a first time mother or previously having breast fed, participating online, having more than two public health nurse visits, and having a positive infant feeding attitude were independently and statistically significantly associated with breast feeding. Among mothers who breast fed, being aged at least 35 years, participating online, having a positive infant feeding attitude and high breast feeding self-efficacy were independently and statistically significantly associated with breast feeding for as long as planned. findings from this study reinforce health inequalities therefore there needs to be a renewed commitment to reducing health inequalities in relation to breast feeding. this study has identified factors associated with initiation and duration of breast feeding that are potentially modifiable through public health interventions. Copyright © 2013 Elsevier Ltd. All rights reserved.

PRMT7 induces epithelial-to-mesenchymal transition and promotes metastasis in breast cancer.

PubMed

Yao, Ruosi; Jiang, Hao; Ma, Yuhui; Wang, Liping; Wang, Lin; Du, Juan; Hou, Pingfu; Gao, Yanyan; Zhao, Li; Wang, Guannan; Zhang, Yu; Liu, Dong-Xu; Huang, Baiqu; Lu, Jun

2014-10-01

Epithelial-to-mesenchymal transition (EMT) enables metastasis. E-cadherin loss is a hallmark of EMT, but there remains an incomplete understanding of the epigenetics of this process. The protein arginine methyltransferase PRMT7 functions in various physiologic processes, including mRNA splicing, DNA repair, and neural differentiation, but its possible roles in cancer and metastasis have not been explored. In this report, we show that PRMT7 is expressed at higher levels in breast carcinoma cells and that elevated PRMT7 mediates EMT and metastasis. PRMT7 could inhibit the expression of E-cadherin by binding to its proximal promoter in a manner associated with altered histone methylation, specifically with elevated H4R3me2s and reduced H3K4me3, H3Ac, and H4Ac, which occurred at the E-cadherin promoter upon EMT induction. Moreover, PRMT7 interacted with YY1 and HDAC3 and was essential to link these proteins to the E-cadherin promoter. Silencing PRMT7 restored E-cadherin expression by repressing H4R3me2s and by increasing H3K4me3 and H4Ac, attenuating cell migration and invasion in MDA-MB-231 breast cancer cells. Overall, our results define PRMT7 as an inducer of breast cancer metastasis and present the opportunity for applying PRMT7-targeted therapeutics to treat highly invasive breast cancers. ©2014 American Association for Cancer Research.

Effect of passive smoking on growth and infection rates of breast-fed and non-breast-fed infants.

PubMed

Yilmaz, Gonca; Hizli, Samil; Karacan, Candemir; Yurdakök, Kadriye; Coşkun, Turgay; Dilmen, Uğur

2009-06-01

The aim of the present study was to determine the effect of passive tobacco smoking on growth and infection rate of infants, and to evaluate whether breast-feeding might be protective against harmful effects of cigarette smoke. A cross-sectional study on 254 6-7-month-old infants was carried out. A questionnaire was given to mothers; and infants' head circumference, bodyweight, height, and urinary cotinine levels were measured. Multivariate analysis of factors influencing lower respiratory tract infections showed that smoking mothers increased the rate by 9.1-fold; breast-feeding decreased it by 3.3-fold; formula feeding at birth increased it by a factor of 15.2; another smoker at home increased it by a factor of 40.1. Multivariate analysis of factors influencing upper respiratory tract infections showed that smoking mothers increased the rate by a factor of 23; early formula feeding increased it by a factor of 62; breast-feeding decreased it by a factor of 5; smoking fathers increased it by a factor of 15. Multivariate analysis of factors influencing otitis media found that smoking mothers and fathers increased it by a factor of 9.4 and 6.15, respectively, and breast-feeding decreased it by a factor of 5.4. Tobacco smoke exposure of infants has negative consequences on growth, otitis media, and upper and lower respiratory tract infections. Breast-feeding promoted the growth of infants who were passively exposed to tobacco smoke and protected them against infections. Smoking should not be permitted in households with infants. When this is impossible, breast-feeding should be promoted to protect the infants against the health hazards of passive smoking.

Curcumin targets breast cancer stem-like cells with microtentacles that persist in mammospheres and promote reattachment

PubMed Central

Charpentier, Monica S.; Whipple, Rebecca A.; Vitolo, Michele I.; Boggs, Amanda E.; Slovic, Jana; Thompson, Keyata N.; Bhandary, Lekhana; Martin, Stuart S.

2014-01-01

Cancer stem-like cells (CSC) and circulating tumor cells (CTCs) have related properties associated with distant metastasis, but the mechanisms through which CSCs promote metastasis are unclear. In this study, we report that breast cancer cell lines with more stem-like properties display higher levels of microtentacles (McTNs), a type of tubulin-based protrusion of the plasma cell membrane which forms on detached or suspended cells and aid in cell reattachment. We hypothesized that CSCs with large numbers of McTNs would more efficiently attach to distant tissues, promoting metastatic efficiency. The naturally occurring stem-like subpopulation of the HMLE breast cell line presents increased McTNs compared to its isogenic non-stem-like subpopulation. This increase was supported by elevated α-tubulin detyrosination and vimentin protein levels and organization. Increased McTNs in stem-like HMLEs promoted a faster initial reattachment of suspended cells that was inhibited by the tubulin-directed drug, colchicine, confirming a functional role for McTN in stem cell reattachment. Moreover, live cell confocal microscopy showed that McTN persist in breast stem cell mammospheres as flexible, motile protrusions on the surface of the mammosphere. While exposed to the environment, they also function as extensions between adjacent cells along cell-cell junctions. We found that treatment with the breast CSC-targeting compound curcumin rapidly extinguished McTN in breast CSC, preventing reattachment from suspension. Together, our results support a model in which breast CSCs with cytoskeletal alterations that promote McTN can mediate attachment and metastasis but might be targeted by curcumin as an anti-metastatic strategy. PMID:24371229

Overexpressed ubiquitin ligase Cullin7 in breast cancer promotes cell proliferation and invasion via down-regulating p53

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guo, Hongsheng; Wu, Fenping; Wang, Yan

2014-08-08

Highlights: • Cullin7 is overexpressed in human breast cancer samples. • Cullin7 stimulated proliferation and invasion of breast cancer cells. • Inhibition of p53 contributes to Cullin7-induced proliferation and invasion. - Abstract: Ubiquitin ligase Cullin7 has been identified as an oncogene in some malignant diseases such as choriocarcinoma and neuroblastoma. However, the role of Cullin7 in breast cancer carcinogenesis remains unclear. In this study, we compared Cullin7 protein levels in breast cancer tissues with normal breast tissues and identified significantly higher expression of Cullin7 protein in breast cancer specimens. By overexpressing Cullin7 in breast cancer cells HCC1937, we found thatmore » Cullin7 could promote cell growth and invasion in vitro. In contrast, the cell growth and invasion was inhibited by silencing Cullin7 in breast cancer cell BT474. Moreover, we demonstrated that Cullin7 promoted breast cancer cell proliferation and invasion via down-regulating p53 expression. Thus, our study provided evidence that Cullin7 functions as a novel oncogene in breast cancer and may be a potential therapeutic target for breast cancer management.« less

Loss of Dickkopf 3 Promotes the Tumorigenesis of Basal Breast Cancer

PubMed Central

Lorsy, Eva; Topuz, Aylin Sophie; Geisler, Cordelia; Stahl, Sarah; Garczyk, Stefan; von Stillfried, Saskia; Hoss, Mareike; Gluz, Oleg; Hartmann, Arndt; Knüchel, Ruth; Dahl, Edgar

2016-01-01

Dickkopf 3 (DKK3) has been associated with tumor suppression of various tumor entities including breast cancer. However, the functional impact of DKK3 on the tumorigenesis of distinct molecular breast cancer subtypes has not been considered so far. Therefore, we initiated a study analyzing the subtype-specific DKK3 expression pattern as well as its prognostic and functional impact with respect to breast cancer subtypes. Based on three independent tissue cohorts including one in silico dataset (n = 30, n = 463 and n = 791) we observed a clear down-regulation of DKK3 expression in breast cancer samples compared to healthy breast tissue controls on mRNA and protein level. Interestingly, most abundant reduction of DKK3 expression was detected in the highly aggressive basal breast cancer subtype. Analyzing a large in silico dataset comprising 3,554 cases showed that low DKK3 mRNA expression was significantly associated with reduced recurrence free survival (RFS) of luminal and basal-like breast cancer cases. Functionally, DKK3 re-expression in human breast cancer cell lines led to suppression of cell growth possibly mediated by up-regulation of apoptosis in basal-like but not in luminal-like breast cancer cell lines. Moreover, ectopic DKK3 expression in mesenchymal basal breast cancer cells resulted in partial restoration of epithelial cell morphology which was molecularly supported by higher expression of epithelial markers like E-Cadherin and down-regulation of mesenchymal markers such as Snail 1. Hence, we provide evidence that down-regulation of DKK3 especially promotes tumorigenesis of the aggressive basal breast cancer subtype. Further studies decoding the underlying molecular mechanisms of DKK3-mediated effects may help to identify novel targeted therapies for this clinically highly relevant breast cancer subtype. PMID:27467270

Do state breastfeeding laws in the USA promote breast feeding?

PubMed

Hawkins, Summer Sherburne; Stern, Ariel Dora; Gillman, Matthew W

2013-03-01

Despite the passage of state laws promoting breast feeding, a formal evaluation has not yet been conducted to test whether and/or what type of laws may increase breast feeding. The enactment of breastfeeding laws in different states in the USA creates a natural experiment. We examined the impact of state breastfeeding laws on breastfeeding initiation and duration as well as on disparities in these infant feeding practices. Using data from the Pregnancy Risk Assessment Monitoring System, we conducted differences-in-differences models to examine breastfeeding status before and after the institution of laws between 2000 and 2008 among 326 263 mothers from 32 states in the USA. For each mother, we coded the presence of two types of state breastfeeding laws. Mothers reported whether they ever breast fed or pumped breast milk (breastfeeding initiation) and, if so, how long they continued. We defined breastfeeding duration as continuing to breast feed for ≥4 weeks. Breastfeeding initiation was 1.7 percentage points higher in states with new laws to provide break time and private space for breastfeeding employees (p=0.01), particularly among Hispanic mothers (adjusted coefficient 0.058). While there was no overall effect of laws permitting mothers to breast feed in any location, among Black mothers we observed increases in breastfeeding initiation (adjusted coefficient 0.056). Effects on breastfeeding duration were in the same direction, but slightly weaker. State laws that support breast feeding appear to increase breastfeeding rates. Most of these gains were observed among Hispanic and Black women and women of lower educational attainment suggesting that such state laws may help reduce disparities in breast feeding.

Obesity-associated Breast Cancer: Analysis of risk factors.

PubMed

Engin, Atilla

2017-01-01

Several studies show that a significantly stronger association is obvious between increased body mass index (BMI) and higher breast cancer incidence. Furthermore, obese women are at higher risk of all-cause and breast cancer specific mortality when compared to non-obese women with breast cancer. In this context, increased levels of estrogens due to excessive aromatization activity of the adipose tissue, overexpression of pro-inflammatory cytokines, insulin resistance, hyperactivation of insulin-like growth factors (IGFs) pathways, adipocyte-derived adipokines, hypercholesterolemia and excessive oxidative stress contribute to the development of breast cancer in obese women. While higher breast cancer risk with hormone replacement therapy is particularly evident among lean women, in postmenopausal women who are not taking exogenous hormones, general obesity is a significant predictor for breast cancer. Moreover, increased plasma cholesterol leads to accelerated tumor formation and exacerbates their aggressiveness. In contrast to postmenopausal women, premenopausal women with high BMI are inversely associated with breast cancer risk. Nevertheless, life-style of women for breast cancer risk is regulated by avoiding the overweight and a high-fat diet. Estrogen-plus-progestin hormone therapy users for more than 5 years have elevated risks of both invasive ductal and lobular breast cancer. Additionally, these cases are more commonly node-positive and have a higher cancer-related mortality. Collectively, in this chapter, the impacts of obesity-related estrogen, cholesterol, saturated fatty acid, leptin and adiponectin concentrations, aromatase activity, leptin and insulin resistance on breast cancer patients are evaluated. Obesity-related prognostic factors of breast cancer also are discussed at molecular basis.

An educational intervention on promotion of breast feeding.

PubMed

Neyzi, O; Olgun, P; Kutluay, T; Uzel, N; Saner, G; Gökçay, G; Taşdelen, E; Akar, U

1991-07-01

This study was designed to search for an effective method to promote exclusive breast feeding among Turkish city women delivering in hospitals. Four hundred and forty-two primiparae with uncomplicated deliveries and with healthy infants with birthweights of greater than 2500 g were exposed to a group educational session on breast feeding after birth, followed by one repeat session at home. Four hundred and ninety-nine women served as controls. All homes were visited monthly for 6 months by independent observers and data relevant to the feeding of the infants were collected. Weight measurements of 176 infants were taken at age 4 months. The study and control mothers were similar in sociodemographic characteristics which reflected a low socio-economic/educational background but relatively good housing conditions. Although significant differences in frequency of exclusive breast feeding were found between the study and control groups, the impact of the intervention was much lower than our expectations and short-lived. Type of feeding was not related to sex or birthweight of the infant, nor to maternal variables. Weight at age 4 months was within normal limits and similar in the study and control groups. It was concluded that lack of up-to-date information on infant feeding was the main obstacle to breast feeding in urban groups in Turkey, and that the impact of an educational intervention limited to the first week after delivery was lost within the first 2 months.

Association of Vascular Endothelial Growth Factor Expression with Tumor Angiogenesis and with Early Relapse in Primary Breast Cancer

PubMed Central

Hoshina, Seigo; Takayanagi, Toshiaki; Tominaga, Takeshi

1994-01-01

Angiogenesis is an independent prognostic indicator in breast cancer. In this report, the relationship between expression of vascular endothclial growth factor (VEGF; a selective mitogen for endothelial cells) and the microvessel density was examined in 103 primary breast cancers. The expression of VEGF was evaluated by immunocytochemical staining using anti‐VEGF antibody. The microvessel density, which was determined by immunostaining for factor VIII antigen, in VEGF‐rich tumors was clearly higher than that in VEGF‐poor tumors (P<0.01). There was a good correlation between VEGF expression and the increment of microvessel density. Furthermore, postoperative survey demonstrated that the relapse‐free survival rate of VEGF‐rich tumors was significantly worse than that of VEGF‐poor tumors. It was suggested that the expression of VEGF is closely associated with the promotion of angiogenesis and with early relapse in primary breast cancer. PMID:7525523

p16(INK4a) promoter methylation and protein expression in breast fibroadenoma and carcinoma.

PubMed

Di Vinci, Angela; Perdelli, Luisa; Banelli, Barbara; Salvi, Sandra; Casciano, Ida; Gelvi, Ilaria; Allemanni, Giorgio; Margallo, Edoardo; Gatteschi, Beatrice; Romani, Massimo

2005-04-10

The potential role of p16(INK4a) methylation in breast cancer is controversial whereas there are no data on fibroadenoma. To assess if inactivation of p16(INK4a) by promoter hypermethylation occurs in this hyperproliferative benign breast lesion or, on the contrary, it is strictly related to the carcinogenic process, we have tested the different histological components of 15 cases of fibroadenoma and the intraductal and infiltrating components of 15 cases of carcinoma and their adjacent non-tumoral epithelium. All samples were obtained by laser-assisted microdissection. The relationship between promoter methylation status, immunohistochemical protein expression and ki67 proliferative activity was evaluated for each lesion. Our data demonstrate that hypermethylation of p16(INK4a) promoter is a common event occurring at similar frequency in all the different histological areas of the benign and malignant breast lesions taken into exam. Conversely, protein p16 expression, although heterogeneously distributed within the section, is considerably higher in breast carcinoma as compared to fibroadenoma in both tumoral and non-tumoral epithelia and stroma. The protein localization was almost exclusively nuclear in fibroadenoma and non-tumoral epithelia whereas, in carcinoma, the staining was both nuclear and cytoplasmic or cytoplasmic alone. Furthermore, in a subset of fibroadenoma with higher proliferative activity, p16 protein expression was substantially decreased as compared to those showing lower proliferation. We did not observe this association in carcinomas. Our data demonstrate that the hypermethylation of the p16(INK4a) promoter is not specifically associated with malignancy and that, on the contrary, the overexpression of p16 and its cytoplasmic sequestration is a feature of breast carcinoma. (c) 2004 Wiley-Liss, Inc.

Targeting fibroblast growth factor receptor in breast cancer: a promise or a pitfall?

PubMed

Bedussi, Francesca; Bottini, Alberto; Memo, Maurizio; Fox, Stephen B; Sigala, Sandra; Generali, Daniele

2014-06-01

Fibroblast growth factors (FGFs) along with their receptors (FGFRs) are involved in several cellular functions, from embryogenesis to metabolism. Because of the ability of FGFR signalling to induce cell proliferation, migration and survival in cancer, these have been found to become overactivated by several mechanisms, including gene amplification, chromosomal translocation and mutations. New evidences indicate that FGFs and FGFRs may act in an oncogenic fashion to promote multiple steps of cancer progression by inducing mitogenic and survival signals, as well as promoting epithelial-to-mesenchymal transition, invasion and tumour angiogenesis. This review focuses on the predictive and prognostic role of FGFRs, the role of FGFR signalling and how it may be most appropriately therapeutically targeted in breast cancer. Activation of the FGFR pathway is a common event in many cancer types and for this reason FGFR is an important potential target in cancer treatment. Relevant literature was reviewed to identify current and future role of FGFR family as a possible guide for selecting those patients who would be poor or good responders to the available or the upcoming target therapies for breast cancer treatment. The success of a personalised medicine approach using targeted therapies ultimately depends on being capable of identifying the patients who will benefit the most from any given drug. Outlining the molecular mechanisms of FGFR signalling and discussing the role of this pathway in breast cancer, we would like to endorse the incorporation of specific patient selection biomakers with the rationale for therapeutic intervention with FGFR-targeted therapy in breast cancer.

A Potent, Imaging Adenoviral Vector Driven by the Cancer-selective Mucin-1 Promoter That Targets Breast Cancer Metastasis

PubMed Central

Huyn, Steven T.; Burton, Jeremy B.; Sato, Makoto; Carey, Michael; Gambhir, Sanjiv S.; Wu, Lily

2009-01-01

Purpose With breast cancer, early detection and proper staging are critical, and will often influence both the treatment regimen and the therapeutic outcome for those affected with this disease. Improvements in these areas will play a profound role in reducing mortality from breast cancer. Experimental Design In this work we developed a breast cancer – targeted serotype 5 adenoviral vector, utilizing the tumor-specific mucin-1 promoter in combination with the two-step transcriptional amplification system, a system used to augment the activity of weak tissue – specific promoters. Results We showed the strong specificity of this tumor-selective adenovirus to express the luciferase optical imaging gene, leading to diagnostic signals that enabled detection of sentinel lymph node metastasis of breast cancer. Furthermore, we were able to target hepatic metastases following systemic administration of this mucin-1 selective virus. Conclusions Collectively, we showed that the amplified mucin-1 promoter – driven vector is able to deliver to and selectively express a desirable transgene in metastatic lesions of breast tumors. This work has strong clinical relevance to current diagnostic staging approaches, and could add to targeted therapeutic strategies to advance the fight against breast cancer. PMID:19366829

NIH study confirms risk factors for male breast cancer

Cancer.gov

Pooled data from studies of about 2,400 men with breast cancer and 52,000 men without breast cancer confirmed that risk factors for male breast cancer include obesity, a rare genetic condition called Klinefelter syndrome, and gynecomastia.

Methylation in promoter regions of PITX2 and RASSF1A genes in association with clinicopathological features in breast cancer patients.

PubMed

Jezkova, Eva; Kajo, Karol; Zubor, Pavol; Grendar, Marian; Malicherova, Bibiana; Mendelova, Andrea; Dokus, Karol; Lasabova, Zora; Plank, Lukas; Danko, Jan

2016-10-15

Breast cancer is a heterogeneous disease with very different responses to therapy and different length of survival. In many cases, however, the determination of the stage and histopathological characteristics of breast cancer is insufficient to predict prognosis and response to treatment for the vast heterogeneity of the disease. To understand the molecular signature of subtypes of breast cancer, we attempted to identify the methylation status of key tumour suppressor gene Ras association (RalGDS/AF-6) domain family member 1 isoform a (RASSF1A) and a member of the paired-like homeodomain transcription factor family which functions in left-right asymmetry development (PITX2) and to correlate results with known clinicopathological features of breast cancer. Formalin-fixed, paraffin-embedded (FFPE) tissues of breast carcinomas (n = 149) were used for DNA extraction. DNA was modified by bisulphite conversion. Detection of the methylation level of the genes mentioned above was performed by methylation-sensitive high-resolution melting assay (MS-HRM). Based on MS-HRM results for RASSF1A and PITX2, we subdivided the samples into four groups according to methylation level (≤50 % methylated, >50 % methylated, 100 % methylated and completely unmethylated alleles). All degrees of methylation status for both genes underwent analysis of dependence with known clinicopathological features, and we found significant associations. In 134 of 149 (89.9 %) primary breast carcinomas, the RASSF1A promoter was methylated. Total hypermethylation of PITX2 was observed in 60 of 135 (44.4 %) breast cancer cases. RASSF1A hypermethylation had significant association with increased age (p < 0.05), tumour grade (p < 0.0001) and stage (p < 0.0001) in the 100 % methylated group. There was significant association of PITX2 hypermethylation with tumour grade (p < 0.0001) and stage (p < 0.0001). Association between the methylation level of both investigated genes and tumour type was

Cohort study of risk factors for breast cancer in post menopausal women.

PubMed

Hartz, Arthur J; He, Tao

2013-01-01

The present study assessed more than 800 potential risk factors to identify new predictors of breast cancer and compare the independence and relative importance of established risk factors. Data were collected by the Women's Health Initiative and included 147,202 women ages 50 to 79 who were enrolled from 1993 to 1998 and followed for 8 years. Analyses performed in 2011 and 2012 used the Cox proportional hazard regression to test the association between more than 800 baseline risk factors and incident breast cancer. Baseline factors independently associated with subsequent breast cancer at the p<0.001 level (in decreasing order of statistical significance) were breast aspiration, family history, age, weight, history of breast biopsies, estrogen and progestin use, fewer live births, greater age at menopause, history of thyroid cancer, breast tenderness, digitalis use, alcohol intake, white race, not restless, no vaginal dryness, relative with prostate cancer, colon polyps, smoking, no breast augmentation, and no osteoporosis. Risk factors previously reported that were not independently associated with breast cancer in the present study included socioeconomic status, months of breast feeding, age at first birth, adiposity measures, adult weight gain, timing of initiation of hormone therapy, and several dietary, psychological, and exercise variables. Family history was not found to alter the risk associated with other factors. These results suggest that some risk factors not commonly studied may be important for breast cancer and some frequently cited risk factors may be relatively unimportant or secondary.

PVT1-derived miR-1207-5p promotes breast cancer cell growth by targeting STAT6.

PubMed

Yan, Chen; Chen, Yaqing; Kong, Weiwei; Fu, Liya; Liu, Yunde; Yao, Qingjuan; Yuan, Yuhua

2017-05-01

Accumulating evidence indicates that ectopic expression of non-coding RNAs are responsible for breast cancer progression. Increased non-coding RNA PVT1, the host gene of microRNA-1207-5p (miR-1207-5p), has been associated with breast cancer proliferation. However, how PVT1 functions in breast cancer is still not clear. In this study, we show a PVT1-derived microRNA, miR-1207-5p, that promotes the proliferation of breast cancer cells by directly regulating STAT6. We first confirm the positive correlated expression pattern between PVT1 and miR-1207-5p by observing consistent induced expression by estrogen, and overexpression in breast cancer cell lines and breast cancer patient specimens. Moreover, silence of PVT1 also decreased miR-1207-5p expression. Furthermore, increased miR-1207-5p expression promoted, while decreased miR-1207-5p expression suppressed, cell proliferation, colony formation, and cell cycle progression in breast cancer cell lines. Mechanistically, a novel target of miR-1207-5p, STAT6, was identified by a luciferase reporter assay. Overexpression of miR-1207-5p decreased the levels of STAT6, which activated CDKN1A and CDKN1B to regulate the cell cycle. We also confirmed the reverse correlation of miR-1207-5p and STAT6 expression levels in breast cancer samples. Therefore, our findings reveal that PVT1-derived miR-1207-5p promotes the proliferation of breast cancer cells by targeting STAT6, which in turn controls CDKN1A and CDKN1B expression. These findings suggest miR-1207-5p might be a potential target for breast cancer therapy. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Risk factors for breast cancer in the breast cancer risk model study of Guam and Saipan.

PubMed

Leon Guerrero, Rachael T; Novotny, Rachel; Wilkens, Lynne R; Chong, Marie; White, Kami K; Shvetsov, Yurii B; Buyum, Arielle; Badowski, Grazyna; Blas-Laguaña, Michelle

2017-10-01

Chamorro Pacific Islanders in the Mariana Islands have breast cancer incidence rates similar to, but mortality rates higher than, those of U.S. women. As breast cancer risk factors of women of the Mariana Islands may be unique because of ethnic and cultural differences, we studied established and suspected risk factors for breast cancer in this unstudied population. From 2010-2013, we conducted retrospective case-control study of female breast cancer (104 cases and 185 controls) among women in the Mariana Islands. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for each of various lifestyle-related factors from logistic regression of breast cancer, in all women and in pre- and postmenopausal women separately. Tests for interaction of risk factors with ethnicity were based on the Wald statistics for cross-product terms. Of the medical and reproductive factors considered - age at menarche, breastfeeding, number of live births, age at first live birth, hormone use, and menopause - only age at first live birth was confirmed. Age at first live birth, among parous women, was higher among cases (mean 24.9 years) than controls (mean 23.2 years); with increased breast cancer risk (OR=2.53; 95% CI, 1.04-6.19 for age≥30y compared to <20y, P for trend=0.01). Of the lifestyle factors -body mass index, waist circumference, physical activity, alcohol and betel-nut intake, and education - only waist circumference (OR=1.65; 95% CI 0.87-3.14 for the highest tertile group compared to the lowest, P for trend=0.04) was significantly associated with breast cancer risk and only in Filipino women. The association with many other established risk factors, such as BMI, hormone use and physical activity, were in the expected direction but were not significant. Associations for family history of breast cancer and alcohol intake were not evident CONCLUSIONS: The results provide a basis for cancer prevention guidance for women in the Mariana Islands. Copyright © 2017 The

PRL-3 promotes breast cancer progression by downregulating p14ARF-mediated p53 expression.

PubMed

Xie, Hua; Wang, Hao

2018-03-01

Prior studies have demonstrated that phosphatase of regenerating liver-3 (PRL-3) serves avital function in cell proliferation and metastasis in breast cancer. However, the molecular mechanisms underlying the function of PRL-3 in breast cancer remain unknown. PRL-3 expression was analyzed in 24 pairs of breast cancer and normal tissues using the reverse transcription-quantitative polymerase chain reaction assay. The results of the present study identified that the expression of PLR-3 in breast cancer tissues was increased 4.2-fold, compared with normal tissues. Notably, overexpression of PRL-3 significantly promoted the proliferation of cancer cells and inhibited endogenous p53 expression by downregulating the expression level of p14 alternate reading frame (p14 ARF ). In addition, decreased expression levels of PRL-3 resulted in decreased breast cancer cell proliferation and increased expression level of p14 ARF . These results suggested that PRL-3 enhances cell proliferation by downregulating p14 ARF expression, which results in decreased levels ofp53. The results of the present study demonstrated that PRL-3 promotes tumor proliferation by affecting the p14 ARF -p53 axis, and that it may serve as a prognostic marker for patients with breast cancer.

Developing a Culturally Responsive Breast Cancer Screening Promotion with Native Hawaiian Women in Churches

ERIC Educational Resources Information Center

Kaopua, Lana Sue

2008-01-01

This article presents findings from research to develop the promotional component of a breast cancer screening program for Native Hawaiian women associated with historically Hawaiian churches in medically underserved communities. The literature on adherence to health recommendations and health promotions marketing guided inquiry on screening…

Prostate-derived Ets factor, an oncogenic driver in breast cancer.

PubMed

Sood, Ashwani K; Geradts, Joseph; Young, Jessica

2017-05-01

Prostate-derived Ets factor (PDEF), a member of the Ets family of transcription factors, differs from other family members in its restricted expression in normal tissues and its unique DNA-binding motif. These interesting attributes coupled with its aberrant expression in cancer have rendered PDEF a focus of increasing interest by tumor biologists. This review provides a current understanding of the characteristics of PDEF expression and its role in breast cancer. The bulk of the evidence is consistent with PDEF overexpression in most breast tumors and an oncogenic role for this transcription factor in breast cancer. In addition, high PDEF expression in estrogen receptor-positive breast tumors showed significant correlation with poor overall survival in several independent cohorts of breast cancer patients. Together, these findings demonstrate PDEF to be an oncogenic driver of breast cancer and a biomarker of poor prognosis in this cancer. Based on this understanding and the limited expression of PDEF in normal human tissues, the development of PDEF-based therapeutics for prevention and treatment of breast cancer is also discussed.

Gasdermin-B promotes invasion and metastasis in breast cancer cells.

PubMed

Hergueta-Redondo, Marta; Sarrió, David; Molina-Crespo, Ángela; Megias, Diego; Mota, Alba; Rojo-Sebastian, Alejandro; García-Sanz, Pablo; Morales, Saleta; Abril, Sandra; Cano, Amparo; Peinado, Héctor; Moreno-Bueno, Gema

2014-01-01

Gasdermin B (GSDMB) belongs to the Gasdermin protein family that comprises four members (GSDMA-D). Gasdermin B expression has been detected in some tumor types such as hepatocarcinomas, gastric and cervix cancers; and its over-expression has been related to tumor progression. At least four splicing isoforms of GSDMB have been identified, which may play differential roles in cancer. However, the implication of GSDMB in carcinogenesis and tumor progression is not well understood. Here, we uncover for the first time the functional implication of GSDMB in breast cancer. Our data shows that high levels of GSDMB expression is correlated with reduced survival and increased metastasis in breast cancer patients included in an expression dataset (>1,000 cases). We demonstrate that GSDMB is upregulated in breast carcinomas compared to normal breast tissue, being the isoform 2 (GSDMB-2) the most differentially expressed. In order to evaluate the functional role of GSDMB in breast cancer two GSDMB isoforms were studied (GSDMB-1 and GSDMB-2). The overexpression of both isoforms in the MCF7 breast carcinoma cell line promotes cell motility and invasion, while its silencing in HCC1954 breast carcinoma cells decreases the migratory and invasive phenotype. Importantly, we demonstrate that both isoforms have a differential role on the activation of Rac-1 and Cdc-42 Rho-GTPases. Moreover, our data support that GSMDB-2 induces a pro-tumorigenic and pro-metastatic behavior in mouse xenograft models as compared to GSDMB-1. Finally, we observed that although both GSDMB isoforms interact in vitro with the chaperone Hsp90, only the GSDMB-2 isoform relies on this chaperone for its stability. Taken together, our results provide for the first time evidences that GSDMB-2 induces invasion, tumor progression and metastasis in MCF7 cells and that GSDMB can be considered as a new potential prognostic marker in breast cancer.

Gasdermin-B Promotes Invasion and Metastasis in Breast Cancer Cells

PubMed Central

Hergueta-Redondo, Marta; Sarrió, David; Molina-Crespo, Ángela; Megias, Diego; Mota, Alba; Rojo-Sebastian, Alejandro; García-Sanz, Pablo; Morales, Saleta; Abril, Sandra; Cano, Amparo; Peinado, Héctor; Moreno-Bueno, Gema

2014-01-01

Gasdermin B (GSDMB) belongs to the Gasdermin protein family that comprises four members (GSDMA-D). Gasdermin B expression has been detected in some tumor types such as hepatocarcinomas, gastric and cervix cancers; and its over-expression has been related to tumor progression. At least four splicing isoforms of GSDMB have been identified, which may play differential roles in cancer. However, the implication of GSDMB in carcinogenesis and tumor progression is not well understood. Here, we uncover for the first time the functional implication of GSDMB in breast cancer. Our data shows that high levels of GSDMB expression is correlated with reduced survival and increased metastasis in breast cancer patients included in an expression dataset (>1,000 cases). We demonstrate that GSDMB is upregulated in breast carcinomas compared to normal breast tissue, being the isoform 2 (GSDMB-2) the most differentially expressed. In order to evaluate the functional role of GSDMB in breast cancer two GSDMB isoforms were studied (GSDMB-1 and GSDMB-2). The overexpression of both isoforms in the MCF7 breast carcinoma cell line promotes cell motility and invasion, while its silencing in HCC1954 breast carcinoma cells decreases the migratory and invasive phenotype. Importantly, we demonstrate that both isoforms have a differential role on the activation of Rac-1 and Cdc-42 Rho-GTPases. Moreover, our data support that GSMDB-2 induces a pro-tumorigenic and pro-metastatic behavior in mouse xenograft models as compared to GSDMB-1. Finally, we observed that although both GSDMB isoforms interact in vitro with the chaperone Hsp90, only the GSDMB-2 isoform relies on this chaperone for its stability. Taken together, our results provide for the first time evidences that GSDMB-2 induces invasion, tumor progression and metastasis in MCF7 cells and that GSDMB can be considered as a new potential prognostic marker in breast cancer. PMID:24675552

The breast cancer fanfare: Sociocultural factors and women's health in Ghana.

PubMed

Tetteh, Dinah A

2017-04-01

Traditional notions of the "full" woman and sociocultural beliefs about gender roles contribute to a unique experience of breast cancer in Africa. I used the critical feminist lens to analyze dis-courses about breast cancer in mainstream Ghanaian media. I found that breast cancer awareness is promoted amidst fanfare and that cultural notions of the female breasts, including their sexual appeal, are implied in breast cancer discourse. This obscures a nuanced understanding of the disease and women's health globally, limits the power of women to name their experiences, and contributes to the late presentation of the dis-ease in sub-Saharan Africa. I discuss the implications of the findings for international, interdisciplinary scholarship.

Occupational exposure and risk of breast cancer

PubMed Central

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 aromatic hydrocarbons and metals are defined environmental factors for breast cancer, particularly at young ages. However, the mechanisms by which occupational factors can promote breast cancer initiation and progression remains to be elucidated. Furthermore, the evaluation of occupational factors for breast cancer, particularly in the workplace, also remains to be explained. The present review summarizes the occupational risk factors and the associated mechanisms involved in breast cancer development, in order to highlight new environmental exposures that could be correlated to breast cancer and to provide new insights for breast cancer prevention in the occupational settings. Furthermore, this review suggests that there is a requirement to include, through multidisciplinary approaches, different occupational exposure risks among those associated with breast cancer development. Finally, the design of new epigenetic biomarkers may be useful to identify the workers that are more susceptible to develop breast cancer. PMID:26998264

Intervention Approaches for Addressing Breast Cancer Disparities among African American Women

PubMed Central

Coughlin, Steven S

2014-01-01

African American women in the U.S. have a higher mortality rate from breast cancer than white women. Black-white differences in survival persist even after accounting for disease stage and tumor characteristics suggesting that the higher rates of breast cancer mortality are due to social factors. Several factors may account for racial differences in breast cancer mortality including socioeconomic factors, access to screening mammography and timely treatment, and biological factors. Efforts to prevent deaths from breast cancer and to address breast cancer disparities have focused on early detection through routine mammography and timely referral for treatment. There is a need for culturally appropriate, tailored health messages for African American women to increase their knowledge and awareness of health behaviors for the early detection of breast cancer. Several promising intervention approaches are reviewed in this article including: 1) the use of cell phone text messaging and smart phone apps to increase breast cancer screening; 2) the use of radio stations that target African American audiences (“black radio”) for health promotion activities; and 3) church-based behavioral interventions to promote breast cancer screening among African American women. PMID:25568890

Lifestyle factors and breast cancer: a case-control study in Kuala Lumpur, Malaysia.

PubMed

Kamarudin, Rozanim; Shah, Shamsul Azhar; Hidayah, Noor

2006-01-01

Breast cancer is the most common female cancer and the commonest cause of death due to cancer for women in Malaysia. This study was performed to identify the relationship with lifestyle factors. A case-control study was conducted among females with breast cancer who came for treatment to the Breast Clinic Hospital Kuala Lumpur in July until September 2004. A total of 203 female patients were recruited as cases along with 203 patients who attended the Outpatient Clinic, Hospital Kuala Lumpur during the study period as the controls. The study showed women who did not exercise regularly to have four times higher risk (adjusted odds ratio is 3.49, 95% CI is 1.84 to 6.62) compared to those who exercised regularly. Women with a high fat diet were also at elevated risk (adjusted odds ratio 3.84, 95% CI is 1.20 to 12.34) compared to those consuming a low fat diet. Women without breast cancer generally had a longer duration of lifetime lactation with a median of thirty-three months compared to women with breast cancer (twenty months, p<0.05). Women who did not take oral contraceptive pills but had breast-fed their child have a 56.0% lower risk (crude odds ratio 0.44, CI is 0.22 to 0.87) compared to women who did not take oral contraceptive pill and also did not breast-feed their child. If they had breast fed for thirteen months and above, they faced a 61.0% lower risk (crude odds ratio 0.39, 95% CI is 0.17 to 0.87). There was a significant inverse trend for lifetime lactation and breast cancer risk. In conclusion certain life styles of women are associated with a higher risk of breast cancer development. Therefore, the promotion of a healthy life style should be emphasized.

Combined caveolin-1 and epidermal growth factor receptor expression as a prognostic marker for breast cancer.

PubMed

Liang, Ya-Nan; Liu, Yu; Wang, Letian; Yao, Guodong; Li, Xiaobo; Meng, Xiangning; Wang, Fan; Li, Ming; Tong, Dandan; Geng, Jingshu

2018-06-01

Previous studies have indicated that caveolin-1 (Cav-1) is able to bind the signal transduction factor epidermal growth factor receptor (EGFR) to regulate its tyrosine kinase activity. The aim of the present study was to evaluate the clinical significance of Cav-1 gene expression in association with the expression of EGFR in patients with breast cancer. Primary breast cancer samples from 306 patients were analyzed for Cav-1 and EGFR expression using immunohistochemistry, and clinical significance was assessed using multivariate Cox regression analysis, Kaplan-Meier estimator curves and the log-rank test. Stromal Cav-1 was downregulated in 38.56% (118/306) of tumor tissues, whereas cytoplasmic EGFR and Cav-1 were overexpressed in 53.92% (165/306) and 44.12% (135/306) of breast cancer tissues, respectively. EGFR expression was positively associated with cytoplasmic Cav-1 and not associated with stromal Cav-1 expression in breast cancer samples; however, low expression of stromal Cav-1 was negatively associated with cytoplasmic Cav-1 expression in total tumor tissues, and analogous results were identified in the chemotherapy group. Multivariate Cox's proportional hazards model analysis revealed that, for patients in the estrogen receptor (ER)(+) group, the expression of stromal Cav-1 alone was a significant prognostic marker of breast cancer. However, in the chemotherapy, human epidermal growth factor receptor 2 (HER-2)(-), HER-2(+) and ER(-) groups, the use of combined markers was more effective prognostic marker. Stromal Cav-1 has a tumor suppressor function, and the combined marker stromal Cav-1/EGFR expression was identified as an improved prognostic marker in the diagnosis of breast cancer. Parenchymal expression of Cav-1 is able to promote EGFR signaling in breast cancer, potentially being required for EGFR-mediated initiation of mitosis.

Surface Expression of TGF-β Docking Receptor GARP Promotes Oncogenesis and Immune Tolerance in Breast Cancer

PubMed Central

Metelli, Alessandra; Wu, Bill X; Fugle, Caroline W; Rachidi, Saleh; Sun, Shaoli; Zhang, Yongliang; Wu, Jennifer; Tomlinson, Stephen; Howe, Philip; Yang, Yi; Garrett-Mayer, Elizabeth; Liu, Bei; Li, Zihai

2016-01-01

GARP encoded by the Lrrc32 gene is the cell surface docking receptor for latent TGF-β which is expressed naturally by platelets and regulatory T cells. Although Lrrc32 is amplified frequently in breast cancer, the expression and relevant functions of GARP in cancer have not been explored. Here we report that GARP exerts oncogenic effects, promoting immune tolerance by enriching and activating latent TGF-β in the tumor microenvironment. We found that human breast, lung and colon cancers expressed GARP aberrantly. In genetic studies in normal mammary gland epithelial and carcinoma cells, GARP expression increased TGF-β bioactivity and promoted malignant transformation in immune deficient mice. In breast carcinoma-bearing mice that were immune competent, GARP overexpression promoted Foxp3+ regulatory T cell activity, which in turn contributed to enhancing cancer progression and metastasis. Notably, administration of a panel of GARP-specific monoclonal antibodies limited metastasis in an orthotopic model of human breast cancer. Overall, these results define the oncogenic effects of the GARP-TGF-β axis in the tumor microenvironment and suggest mechanisms that might be exploited for diagnostic and therapeutic purposes. PMID:27913437

Factors associated with breast MRI use among women with a family history of breast cancer.

PubMed

White, Mary C; Soman, Ashwini; Weinberg, Clarice R; Rodriguez, Juan L; Sabatino, Susan A; Peipins, Lucy A; DeRoo, Lisa; Nichols, Hazel B; Hodgson, M Elizabeth; Sandler, Dale P

2018-05-20

Although annual breast magnetic resonance imaging (MRI) is recommended for women at high risk for breast cancer as an adjunct to screening mammography, breast MRI use remains low. We examined factors associated with breast MRI use in a cohort of women with a family history of breast cancer but no personal cancer history. Study participants came from the Sister Study cohort, a nationwide, prospective study of women with at least 1 sister who had been diagnosed with breast cancer but who themselves had not ever had breast cancer (n = 17 894). Participants were surveyed on breast cancer beliefs, cancer worry, breast MRI use, provider communication, and genetic counseling and testing. Logistic regression was used to assess factors associated with having a breast MRI overall and for those at high risk. Breast MRI was reported by 16.1% and was more common among younger women and those with higher incomes. After adjustment for demographics, ever use of breast MRI was associated with actual and perceived risk. Odds ratios (OR) were 12.29 (95% CI, 8.85-17.06), 2.48 (95% CI, 2.27-2.71), and 2.50 (95% CI, 2.09-2.99) for positive BRCA1/2 test, lifetime breast cancer risk ≥ 20%, and being told by a health care provider of higher risk, respectively. Women who believed they had much higher risk than others or had higher level of worry were twice as likely to have had breast MRI; OR = 2.23 (95% CI, 1.82-2.75) and OR = 1.76 (95% CI, 1.52-2.04). Patterns were similar among women at high risk. Breast cancer risk, provider communication, and personal beliefs were determinants of breast MRI use. To support shared decisions about the use of breast MRI, women could benefit from improved understanding of the chances of getting breast cancer and increased quality of provider communications. © 2018 Wiley Periodicals, Inc.

Acidosis promotes invasiveness of breast cancer cells through ROS-AKT-NF-κB pathway

PubMed Central

Gupta, Subash C.; Singh, Ramesh; Pochampally, Radhika; Watabe, Kounosuke; Mo, Yin-Yuan

2014-01-01

It is well known that acidic microenvironment promotes tumorigenesis, however, the underlying mechanism remains largely unknown. In the present study, we show that acidosis promotes invasiveness of breast cancer cells through a series of signaling events. First, our study indicates that NF-κB is a key factor for acidosis-induced cell invasion. Acidosis activates NF-κB without affecting STAT3 activity; knockdown of NF-κB p65 abrogates the acidosis-induced invasion activity. Next, we show that the activation of NF-κB is mediated through phosphorylation and degradation of IκBα; and phosphorylation and nuclear translocation of p65. Upstream to NF-κB signaling, AKT is activated under acidic conditions. Moreover, acidosis induces generation of reactive oxygen species (ROS) which can be suppressed by ROS scavengers, reversing the acidosis-induced activation of AKT and NF-κB, and invasiveness. As a negative regulator of AKT, PTEN is oxidized and inactivated by the acidosis-induced ROS. Finally, inhibition of NADPH oxidase (NOX) suppresses acidosis-induced ROS production, suggesting involvement of NOX in acidosis-induced signaling cascade. Of considerable interest, acidosis-induced ROS production and activation of AKT and NF-κB can be only detected in cancer cells, but not in non-malignant cells. Together, these results demonstrate a cancer specific acidosis-induced signaling cascade in breast cancer cells, leading to cell invasion. PMID:25504433

Second primary cancers of the breast: incidence and risk factors.

PubMed Central

Hislop, T. G.; Elwood, J. M.; Coldman, A. J.; Spinelli, J. J.; Worth, A. J.; Ellison, L. G.

1984-01-01

Between 1946 and 1976 over 9,000 women with breast cancer were seen within one year of diagnosis at the A. Maxwell Evans Clinic (AMEC) in Vancouver, British Columbia. By 1978, 275 had a subsequent diagnosis of a second primary in the contralateral breast: 100 were diagnosed within 1 year, and 175 after 1 year of the first primary. Two separate comparison groups of AMEC patients with unilateral breast cancer were selected to identify risk factors for bilateral breast cancer and to determine the incidence. The average annual incidence rates for a second primary in the contralateral breast were 5.0, 4.1 and 3.0 per 1,000 women for women less than 45 years, 45-54 years, and over 55 years of age at diagnosis of first primary breast cancer, respectively. These rates remained stable for at least 15 years after the diagnosis of the first primary. Two risk factors were found for bilateral cancer within 1 year of the first primary, histologic diagnosis of lobular carcinoma and absence of pathologic involvement of axillary nodes; one risk factor was found for bilateral breast cancer after 1 year of the first primary, family history of breast cancer. PMID:6691900

How to achieve long-term breast-feeding: factors associated with early discontinuation.

PubMed

Camurdan, Aysu Duyan; Ilhan, Mustafa N; Beyazova, Ufuk; Sahin, Figen; Vatandas, Nilgun; Eminoglu, Sancar

2008-11-01

To evaluate the factors associated with discontinuation of breast-feeding before 12 months in order to make suggestions for achieving long-term breast-feeding. A descriptive cross-sectional study. Gazi University Medical School, Ankara, Turkey. Mothers of 1230 children who discontinued breast-feeding at least 15 d before the last visit were asked to fill out a questionnaire about the discontinuation process. Logistic regression analysis was performed to assess the independent effects of factors that might influence breast-feeding discontinuation. Mean breast-feeding duration of the study group was 11.04 (SD 7.45) months. Introduction of bottle-feeding correlated with discontinuation of breast-feeding (r=0.507, P = 0.001). Important risk factors for discontinuation of breast-feeding before the first 12 months were not exclusively breast-feeding at 3 and 6 months, prematurity, not having a plan about breast-feeding duration and maternity leave duration of breast-feeding in the first and second 6 months were similar, namely the mother's concerns about the sufficiency of breast milk. After 12 months and 18 months the reasons for discontinuation were the baby's unwillingness to eat solid foods while breast-feeding and the mother's perception that 'the baby is old enough', respectively. The factors that improve long-term breast-feeding are successful exclusive breast-feeding in the first few months, intention of the mother to breast-feed and sufficient duration of maternity leave. This study emphasizes the importance of successful breast-feeding counselling during the first few months to achieve the desired long-term breast-feeding.

Curcumin targets breast cancer stem-like cells with microtentacles that persist in mammospheres and promote reattachment.

PubMed

Charpentier, Monica S; Whipple, Rebecca A; Vitolo, Michele I; Boggs, Amanda E; Slovic, Jana; Thompson, Keyata N; Bhandary, Lekhana; Martin, Stuart S

2014-02-15

Cancer stem-like cells (CSC) and circulating tumor cells (CTC) have related properties associated with distant metastasis, but the mechanisms through which CSCs promote metastasis are unclear. In this study, we report that breast cancer cell lines with more stem-like properties display higher levels of microtentacles (McTN), a type of tubulin-based protrusion of the plasma cell membrane that forms on detached or suspended cells and aid in cell reattachment. We hypothesized that CSCs with large numbers of McTNs would more efficiently attach to distant tissues, promoting metastatic efficiency. The naturally occurring stem-like subpopulation of the human mammary epithelial (HMLE) cell line presents increased McTNs compared with its isogenic non-stem-like subpopulation. This increase was supported by elevated α-tubulin detyrosination and vimentin protein levels and organization. Increased McTNs in stem-like HMLEs promoted a faster initial reattachment of suspended cells that was inhibited by the tubulin-directed drug, colchicine, confirming a functional role for McTNs in stem cell reattachment. Moreover, live-cell confocal microscopy showed that McTNs persist in breast stem cell mammospheres as flexible, motile protrusions on the surface of the mammosphere. Although exposed to the environment, they also function as extensions between adjacent cells along cell-cell junctions. We found that treatment with the breast CSC-targeting compound curcumin rapidly extinguished McTN in breast CSC, preventing reattachment from suspension. Together, our results support a model in which breast CSCs with cytoskeletal alterations that promote McTNs can mediate attachment and metastasis but might be targeted by curcumin as an antimetastatic strategy. ©2013 AACR.

Embryonic transcription factor SOX9 drives breast cancer endocrine resistance.

PubMed

Jeselsohn, Rinath; Cornwell, MacIntosh; Pun, Matthew; Buchwalter, Gilles; Nguyen, Mai; Bango, Clyde; Huang, Ying; Kuang, Yanan; Paweletz, Cloud; Fu, Xiaoyong; Nardone, Agostina; De Angelis, Carmine; Detre, Simone; Dodson, Andrew; Mohammed, Hisham; Carroll, Jason S; Bowden, Michaela; Rao, Prakash; Long, Henry W; Li, Fugen; Dowsett, Mitchell; Schiff, Rachel; Brown, Myles

2017-05-30

The estrogen receptor (ER) drives the growth of most luminal breast cancers and is the primary target of endocrine therapy. Although ER blockade with drugs such as tamoxifen is very effective, a major clinical limitation is the development of endocrine resistance especially in the setting of metastatic disease. Preclinical and clinical observations suggest that even following the development of endocrine resistance, ER signaling continues to exert a pivotal role in tumor progression in the majority of cases. Through the analysis of the ER cistrome in tamoxifen-resistant breast cancer cells, we have uncovered a role for an RUNX2-ER complex that stimulates the transcription of a set of genes, including most notably the stem cell factor SOX9, that promote proliferation and a metastatic phenotype. We show that up-regulation of SOX9 is sufficient to cause relative endocrine resistance. The gain of SOX9 as an ER-regulated gene associated with tamoxifen resistance was validated in a unique set of clinical samples supporting the need for the development of improved ER antagonists.

Embryonic transcription factor SOX9 drives breast cancer endocrine resistance

PubMed Central

Jeselsohn, Rinath; Cornwell, MacIntosh; Pun, Matthew; Buchwalter, Gilles; Nguyen, Mai; Bango, Clyde; Huang, Ying; Kuang, Yanan; Paweletz, Cloud; Fu, Xiaoyong; Nardone, Agostina; De Angelis, Carmine; Detre, Simone; Dodson, Andrew; Mohammed, Hisham; Carroll, Jason S.; Bowden, Michaela; Rao, Prakash; Long, Henry W.; Li, Fugen; Dowsett, Mitchell; Schiff, Rachel; Brown, Myles

2017-01-01

The estrogen receptor (ER) drives the growth of most luminal breast cancers and is the primary target of endocrine therapy. Although ER blockade with drugs such as tamoxifen is very effective, a major clinical limitation is the development of endocrine resistance especially in the setting of metastatic disease. Preclinical and clinical observations suggest that even following the development of endocrine resistance, ER signaling continues to exert a pivotal role in tumor progression in the majority of cases. Through the analysis of the ER cistrome in tamoxifen-resistant breast cancer cells, we have uncovered a role for an RUNX2–ER complex that stimulates the transcription of a set of genes, including most notably the stem cell factor SOX9, that promote proliferation and a metastatic phenotype. We show that up-regulation of SOX9 is sufficient to cause relative endocrine resistance. The gain of SOX9 as an ER-regulated gene associated with tamoxifen resistance was validated in a unique set of clinical samples supporting the need for the development of improved ER antagonists. PMID:28507152

Vascular endothelial growth factor and platelet-derived growth factor are potential angiogenic and metastatic factors in human breast cancer.

PubMed

Anan, K; Morisaki, T; Katano, M; Ikubo, A; Kitsuki, H; Uchiyama, A; Kuroki, S; Tanaka, M; Torisu, M

1996-03-01

Angiogenesis is a prerequisite for tumor growth and metastasis. Tumor angiogenesis may be mediated by several angiogenic factors such as vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), transforming growth factor-alpha, and basic fibroblast growth factor. Differential mRNA expressions of VEGF, PDGF (A chain), transforming growth factor-alpha and basic fibroblast growth factor in 32 primary invasive breast tumors were examined by reverse transcriptase-polymerase chain reaction. We analyzed relationships between mRNA expressions of these angiogenic factors and the degree of angiogenesis, tumor size, and metastasis. Quantification of angiogenesis was achieved by the immunohistochemical staining of endothelial cells with antibody to CD31. VEGF and PDGF-A mRNAs were expressed more frequently in breast tumors than in nontumor breast tissues, whereas no difference was found in expression frequency of either transforming growth factor-alpha or basic fibroblast growth factor mRNA. Vascular counts in tumors correlated with each expression frequency of VEGF and PDGF-A mRNA. PDGF-A mRNA was expressed more frequently in tumors with lymph node metastasis than in those without metastasis. Expression of VEGF and PDGF mRNAs detected by reverse transcriptase-polymerase chain reaction in breast tumors correlates with tumor-related characteristics of angiogenesis and metastatic potential. Analysis of these mRNAs by reverse transcriptase-polymerase chain reaction may be useful for assessing the biologic behavior of a breast tumor before surgical treatment.

Autophagy promotes escape from phosphatidylinositol 3-kinase inhibition in estrogen receptor-positive breast cancer.

PubMed

Yang, Wei; Hosford, Sarah R; Traphagen, Nicole A; Shee, Kevin; Demidenko, Eugene; Liu, Stephanie; Miller, Todd W

2018-03-01

Hyperactivation of the PI3K pathway has been implicated in resistance to antiestrogen therapies in estrogen receptor α (ER)-positive breast cancer, prompting the development of therapeutic strategies to inhibit this pathway. Autophagy has tumor-promoting and -suppressing roles and has been broadly implicated in resistance to anticancer therapies, including antiestrogens. Chloroquine (CQ) is an antimalarial and amebicidal drug that inhibits autophagy in mammalian cells and human tumors. Herein, we observed that CQ inhibited proliferation and autophagy in ER + breast cancer cells. PI3K inhibition with GDC-0941 (pictilisib) induced autophagy. Inhibition of autophagy using CQ or RNA interference potentiated PI3K inhibitor-induced apoptosis. Combined inhibition of PI3K and autophagy effectively induced mitochondrial membrane depolarization, which required the BH3-only proapoptotic proteins Bim and PUMA. Treatment with GDC-0941, CQ, or the combination, significantly suppressed the growth of ER + breast cancer xenografts in mice. In an antiestrogen-resistant xenograft model, GDC-0941 synergized with CQ to provide partial, but durable, tumor regression. These findings warrant clinical evaluation of therapeutic strategies to target ER, PI3K, and autophagy for the treatment of ER + breast cancer.-Yang, W., Hosford, S. R., Traphagen, N. A., Shee, K., Demidenko, E., Liu, S., Miller, T. W. Autophagy promotes escape from phosphatidylinositol 3-kinase inhibition in estrogen receptor-positive breast cancer.

Double-Stranded RNA-Binding Protein Regulates Vascular Endothelial Growth Factor mRNA Stability, Translation, and Breast Cancer Angiogenesis▿

PubMed Central

Vumbaca, Frank; Phoenix, Kathryn N.; Rodriguez-Pinto, Daniel; Han, David K.; Claffey, Kevin P.

2008-01-01

Vascular endothelial growth factor (VEGF) is a key angiogenic factor expressed under restricted nutrient and oxygen conditions in most solid tumors. The expression of VEGF under hypoxic conditions requires transcription through activated hypoxia-inducible factor 1 (HIF-1), increased mRNA stability, and facilitated translation. This study identified double-stranded RNA-binding protein 76/NF90 (DRBP76/NF90), a specific isoform of the DRBP family, as a VEGF mRNA-binding protein which plays a key role in VEGF mRNA stability and protein synthesis under hypoxia. The DRBP76/NF90 protein binds to a human VEGF 3′ untranslated mRNA stability element. RNA interference targeting the DRBP76/NF90 isoform limited hypoxia-inducible VEGF mRNA and protein expression with no change in HIF-1-dependent transcriptional activity. Stable repression of DRBP76/NF90 in MDA-MB-435 breast cancer cells demonstrated reduced polysome-associated VEGF mRNA levels under hypoxic conditions and reduced mRNA stability. Transient overexpression of the DRBP76/NF90 protein increased both VEGF mRNA and protein levels synthesized under normoxic and hypoxic conditions. Cells with stable repression of the DRBP76/NF90 isoform showed reduced tumorigenic and angiogenic potential in an orthotopic breast tumor model. These data demonstrate that the DRBP76/NF90 isoform facilitates VEGF expression by promoting VEGF mRNA loading onto polysomes and translation under hypoxic conditions, thus promoting breast cancer growth and angiogenesis in vivo. PMID:18039850

Are breast density and bone mineral density independent risk factors for breast cancer?

PubMed

Kerlikowske, Karla; Shepherd, John; Creasman, Jennifer; Tice, Jeffrey A; Ziv, Elad; Cummings, Steve R

2005-03-02

and breast cancer risk. Breast density is strongly associated with increased risk of breast cancer, even after taking into account reproductive and hormonal risk factors, whereas BMD, although a possible marker of lifetime exposure to estrogen, is not. Thus, a component of breast density that is independent of estrogen-mediated effects may contribute to breast cancer risk.

Risk Factors of Developing Long-Lasting Breast Pain After Breast Cancer Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lundstedt, Dan, E-mail: dan.lundstedt@vgregion.se; Department of Oncology, Sahlgrenska University Hospital, Gothenburg; Gustafsson, Magnus

Purpose: Postoperative radiotherapy decreases breast cancer mortality. However, studies have revealed a long-lasting breast pain among some women after radiotherapy. The purpose of this study was to identify risk factors that contribute to breast pain after breast cancer radiotherapy. Methods and Materials: We identified 1,027 recurrence-free women in two cohorts of Swedish women treated for breast cancer. The women had breast-conserving surgery and postoperative radiotherapy, the breast was treated to 48 Gy in 2.4-Gy fractions or to 50 Gy in 2.0-Gy fractions. Young women received a boost of up to 16 Gy. Women with more than three lymph node metastasesmore » had locoregional radiotherapy. Systemic treatments were given according to health-care guidelines. Three to 17 years after radiotherapy, we collected data using a study-specific questionnaire. We investigated the relation between breast pain and potential risk modifiers: age at treatment, time since treatment, chemotherapy, photon energy, fractionation size, boost, loco-regional radiotherapy, axillary surgery, overweight, and smoking. Results: Eight hundred seventy-seven women (85%) returned the questionnaires. Among women up to 39 years of age at treatment, 23.1% had breast pain, compared with 8.7% among women older than 60 years (RR 2.66; 95% CI 1.33-5.36). Higher age at treatment (RR 0.96; 95% CI 0.94-0.98, annual decrease) and longer time since treatment (RR 0.93; 95% CI 0.88-0.98, annual decrease) were related to a lower occurrence of breast pain. Chemotherapy increased the occurrence of breast pain (RR 1.72; 95% CI 1.19-2.47). In the multivariable model only age and time since treatment were statistically significantly related to the occurrence of breast pain. We found no statistically significant relation between breast pain and the other potential risk modifiers. Conclusions: Younger women having undergone breast-conserving surgery with postoperative radiotherapy report a higher occurrence of long

Evaluation of human epidermal growth factor receptor 2 (HER2) single nucleotide polymorphisms (SNPs) in normal and breast tumor tissues and their link with breast cancer prognostic factors.

PubMed

Furrer, Daniela; Lemieux, Julie; Côté, Marc-André; Provencher, Louise; Laflamme, Christian; Barabé, Frédéric; Jacob, Simon; Michaud, Annick; Diorio, Caroline

2016-12-01

Amplification of the human epidermal growth factor receptor 2 (HER2) gene is associated with worse prognosis and decreased overall survival in breast cancer patients. The HER2 gene contains several polymorphisms; two of the best-characterized HER2 polymorphisms are Ile655Val and Ala1170Pro. The aim of this study was to evaluate the association between these two HER2 polymorphisms in normal breast and breast cancer tissues and known breast cancer prognostic factors in a retrospective cohort study of 73 women with non-metastatic HER2-positive breast cancer. HER2 polymorphisms were assessed in breast cancer tissue and normal breast tissue using TaqMan assay. Ala1170Pro polymorphism in normal breast tissue was associated with age at diagnosis (p = 0.007), tumor size (p = 0.004) and lymphovascular invasion (p = 0.06). Similar significant associations in cancer tissues were observed. No association between the Ile655Val polymorphism and prognostic factors were observed. However, we found significant differences in the distribution of Ile655Val (p = 0.03) and Ala1170Pro (p = 0.01) genotypes between normal breast and breast tumor tissues. This study demonstrates that only the Ala1170Pro polymorphism is associated with prognostic factors in HER2-positive breast cancer patients. Moreover, our results suggest that both HER2 polymorphisms could play a significant role in carcinogenesis in non-metastatic HER2-positive breast cancer women. Copyright © 2016 Elsevier Ltd. All rights reserved.

[The social hygienic factors of the prevalence of children's breast feeding].

PubMed

Amirov, N Kh; Mingazova, E N; Gaĭnutdinova, L I

2008-01-01

The study of the impact of family social hygienic factors on the breast feeding process was carried out on the basis of the sociological survey of 394 women of fertilization age from the "Kazanorgsintez" staff. The influence on the breast feeding duration of such factors as the family structure, the living conditions, the family income level is revealed. The ensued characteristics of breast feeding resulted from the impact of the practice of breast feeding developed in families.

[Risk factors in the development of breast cancer, state of Mexico].

PubMed

Aguilar Cordero, M J; Neri Sánchez, M; Padilla López, C A; Pimentel Ramírez, M L; García Rillo, A; Sánchez López, A M

2012-01-01

Breast cancer is one of the most frequent diseases in women today, and its social impact is devastating. The risk factors focused on in recent research are mainly hormonal, genetic, and environmental though toxic habits, overweight, and obesity have also been studied. In contrast, protective factors against breast cancer include breastfeeding and daily exercise. To ascertain the risk factors for the women with breast cancer in our study sample. A study of cases and controls was performed on 115 women diagnosed with breast cancer and on 115 healthy women, who had been patients at the National Cancer Institute ISSEMYM in Mexico from January to December 2011. Information was collected from the women in the sample pertaining to their family history of cancer, personal background, life style, and body mass index (BMI). Breast cancer risk was estimated with multivariate logistic regression models and the chi-square test. It was found that there was a greater risk of breast cancer in overweight or obese women who did not do any physical exercise and either who had breastfed their children for a very short time or who had not breastfed them at all. No significant differences were found between breast cancer and toxic habits. The results of our study found a direct relation between breast cancer and overweight, obesity, and physical inactivity. Breastfeeding during the first months of the baby's life was found to be a protective factor against breast cancer.

Cadmium promotes the proliferation of triple-negative breast cancer cells through EGFR-mediated cell cycle regulation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wei, Zhengxi, E-mail: weizhengxi@gmail.com; Song, Xiulong; Shaikh, Zahir A., E-mail: zshaikh@uri.edu

Cadmium (Cd) is a carcinogenic metal which is implicated in breast cancer by epidemiological studies. It is reported to promote breast cancer cell growth in vitro through membrane receptors. The study described here examined Cd-mediated growth of non-metastatic human breast cancer derived cells that lack receptors for estrogen, progesterone, and HER2. Treatment of triple-negative HCC 1937 cells with 0.1–0.5 μM Cd increased cell growth by activation of AKT and ERK. Accelerated cell cycle progression was achieved by increasing the levels of cyclins A, B, and E, as well as those of CDKs 1 and 2. Although triple negative cells lackmore » estrogen receptor, they express high levels of EGFR. Therefore, further studies on HCC 1937 and another triple-negative cell line, HCC 38, were conducted using specific siRNA and an inhibitor of EGFR to determine whether EGFR was responsible for mediating the effect of Cd. The results revealed that in both cell types EGFR was not only activated upon Cd treatment, but was also essential for the downstream activation of AKT and ERK. Based on these observations, it is concluded that, in breast cancer cells lacking estrogen receptor, sub-micromolar concentration of Cd can promote cell proliferation. Furthermore, that EGFR plays a critical role in this process. - Highlights: • Sub-micromolar concentrations of Cd promote cell growth in breast cancer cells that lack ER, PR, and HER2. • The increase in cell number is not due to reduction in apoptosis. • Growth promotion involves AKT and ERK signaling and downstream stimulation of cell cycle progression. • Initiation of cell growth by Cd occurs at the cell membrane and requires the activation of EGFR.« less

Apoptosis-linked gene 2 promotes breast cancer growth and metastasis by regulating the cytoskeleton

PubMed Central

Qin, Juan; Li, Dengwen; Zhou, Yunqiang; Xie, Songbo; Du, Xin; Hao, Ziwei; Liu, Ruming; Liu, Xinqi; Liu, Min; Zhou, Jun

2017-01-01

Breast cancer is the most prevalent cancer in women. Although it begins as local disease, breast cancer frequently metastasizes to the lymph nodes and distant organs. Therefore, novel therapeutic targets are needed for the management of this disease. Apoptosis-linked gene 2 (ALG-2) is a calcium-binding protein crucial for diverse physiological processes and has recently been implicated in cancer development. However, it remains unclear whether this protein is involved in the pathogenesis of breast cancer. Here, we demonstrate that the expression of ALG-2 is significantly upregulated in breast cancer tissues and is correlated with clinicopathological characteristics indicative of tumor malignancy. Our data further show that ALG-2 stimulates breast cancer growth and metastasis in mice. ALG-2 also promotes breast cancer cell proliferation, survival, and motility in vitro. Mechanistic data reveal that ALG-2 disrupts the localization of centrosome proteins, resulting in spindle multipolarity and chromosome missegregation. In addition, ALG-2 drives the polarization and migration of breast cancer cells by facilitating the rearrangement of microtubules and microfilaments. These findings reveal a critical role for ALG-2 in the pathogenesis of breast cancer and have important implications for its diagnosis and therapy. PMID:27926525

Breast Cancer in Australian Indigenous Women: Incidence, Mortality, and Risk Factors

PubMed Central

Tapia, Kriscia A; Garvey, Gail; Entee, Mark Mc; Rickard, Mary; Brennan, Patrick

2017-01-01

The Indigenous people of Australia face significant health gaps compared with the general population, with lower life expectancies, higher rates of death, and chronic illness occurring more often than in non-indigenous Australians. Cancer is the second largest contributor to the burden of disease with breast cancer being the most common invasive cancer diagnosed for females. Despite a lower breast cancer incidence compared with non-indigenous women, fatalities occur at an elevated rate and breast cancers have an earlier age of onset. For indigenous women there are also more advanced and distant tumours at diagnosis, fewer hospitalisations for breast cancer, and lower participation in breast screening. Concomitantly there are demographic, socio-economic and lifestyle factors associated with breast cancer risks that are heavily represented within Indigenous communities. The aim of this two-part narrative review is to examine the available evidence on breast cancer and its risk factors in Australian Indigenous women. Part One presents a summary of the latest incidence, survival and mortality data. Part Two presents the risk factors most strongly associated with breast cancer including age, place of residence, family risk, genetics, reproductive history, tobacco use, alcohol intake, physical activity, participation in screening and breast density. With increasing emphasis on personalized health care, a clear understanding of breast cancer incidence, survival, mortality, and causal agents within the Indigenous population is required if breast cancer prevention and management is to be optimized for Indigenous Australians. PMID:28545182

Breast-feeding at 12 months of age and dietary habits among breast-fed and non-breast-fed infants.

PubMed

Lande, Britt; Andersen, Lene Frost; Veierød, Marit B; Baerug, Anne; Johansson, Lars; Trygg, Kerstin U; Bjørneboe, Gunn-Elin Aa

2004-06-01

To analyse factors associated with breast-feeding and use of sweetened drinks at 12 months, and to compare dietary habits among breast-fed and non-breast-fed infants. Data were collected by a semi-quantitative food-frequency questionnaire filled in by the parents. National dietary survey in Norway. In total, 1932 12-month-old infants were included. At 12 months, 36% of the infants were breast-fed. The odds of breast-feeding at this age were more than doubled both for mothers > or =35 years compared with mothers <25 years and for mothers in the highest educational group compared with mothers in the lowest. A negative association was found for maternal smoking, and the odds of breast-feeding were 40% lower for mothers who smoked than for non-smokers. Some dietary differences were observed between breast-fed and non-breast-fed infants apart from intake of milk. In particular, breast-fed infants had a significantly lower daily intake of sweetened drinks than non-breast-fed infants and a 16% lower mean daily intake of added sugars (P<0.001). Furthermore, breast-fed infants had 30% higher odds of not receiving sweetened drinks daily, compared with non-breast-fed infants. Maternal age, education and smoking status were important factors for breast-feeding at 12 months. Breast-fed infants had lower intakes of sweetened drinks and added sugars than non-breast-fed infants. From a public health perspective, continued promotion of breast-feeding is needed to reduce inequalities in breast-feeding. Moreover, prevention of high intakes of sweetened drinks and added sugars should start in infancy.

[Incidence and surgical wound infection risk factors in breast cancer surgery].

PubMed

Lefebvre, D; Penel, N; Deberles, M F; Fournier, C

2000-11-18

In order to evaluate occurrence and risk factors for wound infection (WI) in breast cancer surgery, we carried out a prospective study. From September 1996 through April 1997, an infection control physician prospectively evaluated 542 wounds of all patients having breast cancer surgery at the Oscar Lambret Cancer Center. WI was defined as a wound with pus. Antibiotic prophylaxis was given in case of immediate breast reconstruction. Statistical evaluation was performed using the c < or = test for categorial data and non-parametric Mann-Whitney test for continuous data. In univariate analysis, differences were considered significant at p < 0.01. The overall WI rate was 3.51% (19/352). In univariate analysis, risk factors for WI were: total preoperative hospital stay (p = 0.01), previous chemotherapy (p = 0.01), previous oncologic surgery (p = 0.03) and immediate breast reconstruction (p = 0.002). In mutivariate analysis, we observed two independent predictive factors for WI: previous chemotherapy (p = 0.05) and immediate breast reconstruction (p = 0.02). Previous anticancer chemotherapy was a major risk factor. In these cases, a phase III trial could confirm efficacy of standard antibiotic prophylaxis. Breast reconstruction was the second major risk factor. Standard antibiotic prophylaxis (used in our study) was insufficient.

A breast-feeding promotion and support program a randomized trial in The Netherlands.

PubMed

Kools, Els J; Thijs, Carel; Kester, Arnold D M; van den Brandt, Piet A; de Vries, Hein

2005-01-01

In the Netherlands, the initiation rate of breast-feeding (BF) was 80% in 2002, but only 35% of the mothers continued to breast-feed for 3 months. This study examined the effectiveness of a breast-feeding promotion program to increase the continuation of breast-feeding. A cluster-randomized intervention trial was used. Ten child health care centers in three regions of the home health care were randomly allocated to the program or usual care. Elements in the program were health counseling, measures to enhance cooperation, early signaling of breast-feeding problems and continuity of care, and lactation consultancy. Pregnant mothers who applied for home health care in the intervention or usual care regions were enrolled and were followed up from pregnancy until 6 months postpartum (n = 683). The primary outcome measure was the continuation of breast-feeding until at least 3 months. The 3-month breast-feeding rate was 32% in the intervention and 38% in the control groups (OR = 0.79, 95% CI = 0.58-1.08). The program was not effective. We discuss possible explanations from the design and execution of the trial and give some points for improvement of our program, such as the categories of caregivers involved and the number and duration of contacts after parturition.

ICI 182,780 induces P-cadherin overexpression in breast cancer cells through chromatin remodelling at the promoter level: a role for C/EBPbeta in CDH3 gene activation.

PubMed

Albergaria, André; Ribeiro, Ana Sofia; Pinho, Sandra; Milanezi, Fernanda; Carneiro, Vítor; Sousa, Bárbara; Sousa, Sónia; Oliveira, Carla; Machado, José Carlos; Seruca, Raquel; Paredes, Joana; Schmitt, Fernando

2010-07-01

CDH3/P-cadherin is a classical cadherin. Overexpression of which has been associated with proliferative lesions of high histological grade, decreased cell polarity and poor survival of patients with breast cancer. In vitro studies showed that it can be up-regulated by ICI 182,780, suggesting that the lack of ERalpha signalling is responsible for the aberrant P-cadherin overexpression and for its role in inducing breast cancer cell invasion and migration. However, the mechanism by which ER-signalling inhibition leads to P-cadherin expression is still unknown. The aim of this study was to explore the molecular mechanism linking the ERalpha-signalling and P-cadherin-regulated expression in breast cancer cell lines. This study showed that ICI 182,780 is able to increase CDH3 promoter activity, inducing high levels of the active chromatin mark H3 lysine 4 dimethylation. We also observed, for the first time, that the transcription factor C/EBPbeta is able to up-regulate CDH3 promoter activity in breast cancer cells. Moreover, we showed that the expression of P-cadherin and C/EBPbeta are highly associated in human breast carcinomas and linked with a worse prognosis of breast cancer patients. This study demonstrates the existence of an epigenetic regulation by which ICI 182,780 up-regulates P-cadherin expression in MCF-7/AZ breast cancer cells through chromatin remodelling at CDH3 promoter, bringing forward the growing evidence that ERalpha signalling-abrogation by anti-oestrogens is able to induce the expression of ERalpha-repressed genes which, in the appropriate cell biology context, may contribute to a breast cancer cell invasion phenotype.CDH3 GenBank accession no. NT_010498.

Personality factors and breast cancer development: a prospective longitudinal study.

PubMed

Bleiker, E M; van der Ploeg, H M; Hendriks, J H; Adèr, H J

1996-10-16

It has been estimated that approximately 25% of all breast cancers in women can be explained by currently recognized somatic (i.e., hereditary and physiologic) risk factors. It has also been hypothesized that psychological factors may play a role in the development of breast cancer. We investigated the extent to which personality factors, in addition to somatic risk factors, may be associated with the development of primary breast cancer. We employed a prospective, longitudinal study design. From 1989 through 1990, a personality questionnaire was sent to all female residents of the Dutch city of Nijmegen who were 43 years of age or older. This questionnaire was sent as part of an invitation to participate in a population-based breast cancer screening program. Women who developed breast cancer among those who returned completed questionnaires were compared with women without such a diagnosis in regard to somatic risk factors and personality traits, including anxiety, anger, depression, rationality, anti-emotionality (i.e., an absence of emotional behavior or a lack of trust in one's own feelings), understanding, optimism, social support, and the expression and control of emotions. Conditional logistic regression analysis was used to identify variables that could best explain group membership (i.e., belonging to the case [breast cancer] or the control [without disease] group). Personality questionnaires were sent to 28 940 women, and 9705 (34%) were returned in such a way that they could be used for statistical analyses. Among the 9705 women who returned useable questionnaires, 131 were diagnosed with breast cancer during the period from 1989 through 1994. Seven hundred seventy-one age-matched control subjects (up to six per case patient) were selected for the analyses. Three variables were found to be statistically significantly associated with an increased risk of breast cancer: 1) having a first-degree family member with breast cancer (versus not having an

Factors affecting receipt of chemotherapy in women with breast cancer

PubMed Central

Morimoto, Libby; Coalson, Jenna; Mowat, Fionna; O’Malley, Cynthia

2010-01-01

Aims: To review literature describing factors associated with receipt of chemotherapy for breast cancer, to better understand what factors are most relevant to women’s health and whether health disparities are apparent, and to assess how these factors might affect observational studies and outcomes research. Patterns of care for metastatic breast cancer, for which no standard-of-care exists, were of particular interest. Methods: Relevant studies written in English, Italian, French, or Spanish, published in 2000 or later, were identified through MEDLINE and reviewed. Review articles and clinical trials were excluded; all observational studies and surveys were considered. Articles were reviewed for any discussion of patient characteristics, hospital/physician/insurance characteristics, psychosocial characteristics, and clinical characteristics affecting receipt of chemotherapy by breast cancer patients. Results: In general, factors associated with increased likelihood of receiving chemotherapy included younger age, being Caucasian, having good general health and few co-morbidities, having more severe clinical disease, having responded well to previous treatment, and having breast cancer that is estrogen- or progesterone-receptor-negative. Many of the clinical factors found to increase the likelihood of receiving chemotherapy were consistent with current oncology guidelines. Of the relevant 19 studies identified, only six (32%) reported data specific to metastatic cancer; most studies aggregated women with stage I–IV for purposes of analysis. Conclusion: Studies of patterns of care in breast cancer treatment can help identify challenges in health care provided to particular subgroups of women and can aid researchers in designing studies that account for such factors in clinical and outcomes research. Although scarce, studies evaluating only women with metastatic breast cancer indicate that factors affecting decisions related to receipt of chemotherapy are similar

Risk factors for breast cancer in postmenopausal Caucasian and Chinese-Canadian women.

PubMed

Tam, Carolyn Y; Martin, Lisa J; Hislop, Gregory; Hanley, Anthony J; Minkin, Salomon; Boyd, Norman F

2010-01-01

Striking differences exist between countries in the incidence of breast cancer. The causes of these differences are unknown, but because incidence rates change in migrants, they are thought to be due to lifestyle rather than genetic differences. The goal of this cross-sectional study was to examine breast cancer risk factors in populations with different risks for breast cancer. We compared breast cancer risk factors among three groups of postmenopausal Canadian women at substantially different risk of developing breast cancer - Caucasians (N = 413), Chinese women born in the West or who migrated to the West before age 21 (N = 216), and recent Chinese migrants (N = 421). Information on risk factors and dietary acculturation were collected by telephone interviews using questionnaires, and anthropometric measurements were taken at a home visit. Compared to Caucasians, recent Chinese migrants weighed on average 14 kg less, were 6 cm shorter, had menarche a year later, were more often parous, less often had a family history of breast cancer or a benign breast biopsy, a higher Chinese dietary score, and a lower Western dietary score. For most of these variables, Western born Chinese and early Chinese migrants had values intermediate between those of Caucasians and recent Chinese migrants. We estimated five-year absolute risks for breast cancer using the Gail Model and found that risk estimates in Caucasians would be reduced by only 11% if they had the risk factor profile of recent Chinese migrants for the risk factors in the Gail Model. Our results suggest that in addition to the risk factors in the Gail Model, there likely are other factors that also contribute to the large difference in breast cancer risk between Canada and China.

Estrogen receptor alpha and nuclear factor Y coordinately regulate the transcription of the SUMO-conjugating UBC9 gene in MCF-7 breast cancer cells.

PubMed

Ying, Shibo; Dünnebier, Thomas; Si, Jing; Hamann, Ute

2013-01-01

UBC9 encodes a protein that conjugates small ubiquitin-related modifier (SUMO) to target proteins thereby changing their functions. Recently, it was noted that UBC9 expression and activity play a role in breast tumorigenesis and response to anticancer drugs. However, the underlying mechanism is poorly understood. To investigate the transcriptional regulation of the UBC9 gene, we identified and characterized its promoter and cis-elements. Promoter activity was tested using luciferase reporter assays. The binding of transcription factors to the promoter was detected by chromatin immunoprecipitation (ChIP), and their functional role was confirmed by siRNA knockdown. UBC9 mRNA and protein levels were measured by quantitative reverse transcription PCR and Western blot analysis, respectively. An increased expression of UBC9 mRNA and protein was found in MCF-7 breast cancer cells treated with 17β-estradiol (E2). Analysis of various deletion mutants revealed a 137 bp fragment upstream of the transcription initiation site to be sufficient for reporter gene transcription. Mutations of putative estrogen receptor α (ER-α) (one imperfect estrogen response element, ERE) and/or nuclear factor Y (NF-Y) binding sites (two CCAAT boxes) markedly reduced promoter activity. Similar results were obtained in ER-negative MDA-MB-231 cells except that the ERE mutation did not affect promoter activity. Additionally, promoter activity was stimulated upon E2 treatment and overexpression of ER-α or NF-YA in MCF-7 cells. ChIP confirmed direct binding of both transcription factors to the UBC9 promoter in vivo. Furthermore, UBC9 expression was diminished by ER-α and NF-Y siRNAs on the mRNA and protein levels. In conclusion, we identified the proximal UBC9 promoter and provided evidence that ER-α and NF-Y regulate UBC9 expression on the transcriptional level in response to E2 in MCF-7 cells. These findings may contribute to a better understanding of the regulation of UBC9 in ER

Prevalence and factors influencing exclusive breast-feeding in Rajavithi Hospital.

PubMed

Plewma, Phawinee

2013-03-01

The aim of the present study was to identify the prevalence of exclusive breast-feeding after 2,4, and 6 months in Rajavithi Hospital. The present study evaluated the factors associated with discontinuing breast-feeding before the first two months of life in order to target early nursing interventions to encourage and support continued breast-feeding and increase the exclusive breast-feeding rate. From September 2010 to May 2011, mothers were interviewed prior to hospital discharge from the maternity ward and follow-up phone calls were made after 2,4 and 6 months postpartum. The prevalence of exclusive breast-feeding after 2, 4 and 6 months was 57.9% (252 out of 435), 32.0% (139 out of 435) and 4.8% (21 out of435) respectively. At 2 months postpartum, multivariate analysis was carried out to identify whether maternal obesity and breast-feeding intervals of more than 3 hours had a statistically significant association with cessation of breast-feeding. The most common reason for cessation of exclusive breast-feeding by mothers was their return to work. The prevalence of exclusive breast-feeding at 2, 4, and 6 months was 57.9%, 32.0% and 4.8%, respectively. Maternal obesity, and maternal breast-feeding for intervals of more than 3 hours prior to hospital discharge were risk factors of early breast-feeding cessation at 2 months postpartum. This is an area on which we would target nursing interventions to prevent early unintended weaning.

Urban-rural disparity of breast cancer and socioeconomic risk factors in China.

PubMed

Fei, Xufeng; Wu, Jiaping; Kong, Zhe; Christakos, George

2015-01-01

Breast cancer is one of the most commonly diagnosed cancers worldwide. The primary aim of this work is the study of breast cancer disparity among Chinese women in urban vs. rural regions and its associations with socioeconomic factors. Data on breast cancer incidence were obtained from the Chinese cancer registry annual report (2005-2009). The ten socioeconomic factors considered in this study were obtained from the national population 2000 census and the Chinese city/county statistical yearbooks. Student's T test was used to assess disparities of female breast cancer and socioeconomic factors in urban vs. rural regions. Pearson correlation and ordinary least squares (OLS) models were employed to analyze the relationships between socioeconomic factors and cancer incidence. It was found that the breast cancer incidence was significantly higher in urban than in rural regions. Moreover, in urban regions, breast cancer incidence remained relatively stable, whereas in rural regions it displayed an annual percentage change (APC) of 8.55. Among the various socioeconomic factors considered, breast cancer incidence exhibited higher positive correlations with population density, percentage of non-agriculture population, and second industry output. On the other hand, the incidence was negatively correlated with the percentage of population employed in primary industry. Overall, it was observed that higher socioeconomic status would lead to a higher breast cancer incidence in China. When studying breast cancer etiology, special attention should be paid to environmental pollutants, especially endocrine disruptors produced during industrial activities. Lastly, the present work's findings strongly recommend giving high priority to the development of a systematic nationwide breast cancer screening program for women in China; with sufficient participation, mammography screening can considerably reduce mortality among women.

From bioactive substances to research on breast-feeding promotion.

PubMed

Morrow, A L; Guerrero, M L

2001-01-01

Despite known health benefits, exclusive breast-feeding for at least 4 months is uncommon in many countries. In Mexico, most mothers initiate breast-feeding but few breast-feed exclusively. The objective was to examine the effectiveness of home visits by lay peer counselors to increase exclusive breast-feeding among mothers in a periurban area of Mexico. An ethnographic assessment conducted in 1994 that identified key maternal beliefs, practices, and needs was used to guide educational strategies. Lay counselors were recruited from the same community and trained by La Leche League. From March 1995 through September 1996, pregnant women were identified by community census and invited to participate. Women were enrolled into a randomized, controlled study of 3 groups: no intervention (control), 3 visits, and 6 visits during pregnancy and early postpartum. Data collection was performed by a social worker apart from the counselors. Exclusive breast-feeding was defined by WHO criteria. The study enrolled 130 women; 52 were in the 3-visit group, 44 in the 6-visit group, and 34 in the control group. Study groups did not differ in the maternal characteristics or initiation of breast-feeding (96%). At 3 months postpartum, exclusive breast-feeding was practiced by only 12% of controls vs. 52% in the 3-visit group and 67% in the 6-visit group (P < 0.001, log rank test). In the first 3 months, significantly (P = 0.037) fewer intervention than control infants had an episode of diarrhea (11% vs. 26%, respectively). Intervention effectiveness was independent of maternal factors or birth hospital. This unique experimental study demonstrated a dramatic increase in exclusive breast-feeding and a significant reduction in infant illness in an urban community through well-designed maternal support including early intervention and repeated contact.

The role of dietary factors in prevention and progression of breast cancer.

PubMed

Rossi, Roberta Elisa; Pericleous, Marinos; Mandair, Dalvinder; Whyand, Tara; Caplin, Martyn Evan

2014-12-01

Breast cancer (BC) is the leading global cause of cancer-related death in women. There is growing evidence for a role for dietary factors in BC pathophysiology. The aim of the present review was to evaluate the impact of dietary factors in BC risk. Bibliographical searches were performed in PubMed, using the following terms: "nutrition and breast cancer", "nutrition and breast carcinoma", "dietary factors and breast cancer", "risk factors and breast cancer", "diet and breast cancer, "breast cancer epidemiology", "breast cancer and prevention". Consumption of well-done red meat appears to be associated with increased risk of BC, whereas fish may be protective. Total cholesterol, triglyceride levels and glycaemic load should be monitored and controlled in at risk populations because they may be associated with increased risk of BC, although the exact mechanisms involved are not clear. Alcohol intake should be minimized since it is a risk factor for BC. High intake of polyphenol/phyto-oestrogen -rich food (i.e. flavonoids, soya products), as well as fibres, fruits and vegetables, may have potential protective effects against BC occurrence but the results might vary according to hormonal status. Vitamin D supplements appear protective against BC development and similarly other vitamins and oligo-elements might decrease BC risk, although further large prospective studies are required. There exist increasing evidence that dietary factors can play an important role in both the development and prevention of BC. Large randomized clinical and epidemiological studies are required but are difficult to design due to the number of variable factors. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Hypoxia-induced secretion of TGF-β1 in mesenchymal stem cell promotes breast cancer cell progression.

PubMed

Hung, Shun-Pei; Yang, Muh-Hwa; Tseng, Kuo-Fung; Lee, Oscar K

2013-01-01

In solid tumors, a decreased oxygen and nutrient supply creates a hypoxic microenvironment in the central region. This hypoxic condition induces molecular responses of normal and cancer cells in the local area, including angiogenesis, metabolic changes, and metastasis. In addition, other cells including mesenchymal stem cells (MSCs) have been reported to be recruited into the hypoxic area of solid tumors. In our previous study, we found that hypoxic condition induces the secretion of growth factors and cytokines in MSCs, and here we demonstrate that elevated secretion of transforming growth factor-β1 (TGF-β1) by MSCs under hypoxia promotes the growth, motility, and invasive ability of breast cancer cells. It was found that TGF-β1 promoter activity was regulated by hypoxia, and the major hypoxia-regulated element was located between bp -1030 to -666 in front of the TGF-β1 promoter region. In ChIP assay, the results revealed that HIF-1 was bound to the hypoxia response element (HRE) of TGF-β1 promoter. Collectively, the results indicate that hypoxia microenvironment can enhance cancer cell growth through the paracrine effects of the MSCs by driving their TGF-β1 gene expression and secretion. Therefore, extra caution has to be exercised when considering hypoxia pretreatment of MSCs before cell transplantation into patients for therapeutic purposes, particularly in patients susceptible to tumor growth.

Novel Angiogenic Domains: Use in Identifying Unique Transforming and Tumor Promoting Pathways in Human Breast Cancer

DTIC Science & Technology

2004-10-01

Cancer PRINCIPAL INVESTIGATOR: Thomas F. Deuel, M.D. CONTRACTING ORGANIZATION: The Scripps Research Institute...NUMBER Novel Angiogenic Domains: Use in Identifying Unique Transforming and Tumor Promoting Pathways in Human Breast Cancer 5b. GRANT NUMBER DAMD17...SUPPLEMENTARY NOTES 14. ABSTRACT Breast cancers in humans often grow slowly or even remain undetectable for long periods of time only to

Gpr132 sensing of lactate mediates tumor–macrophage interplay to promote breast cancer metastasis

PubMed Central

Chen, Peiwen; Zuo, Hao; Xiong, Hu; Kolar, Matthew J.; Chu, Qian; Saghatelian, Alan; Siegwart, Daniel J.; Wan, Yihong

2017-01-01

Macrophages are prominent immune cells in the tumor microenvironment that exert potent effects on cancer metastasis. However, the signals and receivers for the tumor–macrophage communication remain enigmatic. Here, we show that G protein-coupled receptor 132 (Gpr132) functions as a key macrophage sensor of the rising lactate in the acidic tumor milieu to mediate the reciprocal interaction between cancer cells and macrophages during breast cancer metastasis. Lactate activates macrophage Gpr132 to promote the alternatively activated macrophage (M2)-like phenotype, which, in turn, facilitates cancer cell adhesion, migration, and invasion. Consequently, Gpr132 deletion reduces M2 macrophages and impedes breast cancer lung metastasis in mice. Clinically, Gpr132 expression positively correlates with M2 macrophages, metastasis, and poor prognosis in patients with breast cancer. These findings uncover the lactate-Gpr132 axis as a driver of breast cancer metastasis by stimulating tumor–macrophage interplay, and reveal potential new therapeutic targets for breast cancer treatment. PMID:28049847

EPO-independent functional EPO receptor in breast cancer enhances estrogen receptor activity and promotes cell proliferation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Reinbothe, Susann; Larsson, Anna-Maria; Vaapil, Marica

Highlights: • New anti-human EPOR antibody confirms full-length EPOR expression in breast cancer cells. • Proliferation of breast cancer cells is not affected by rhEPO treatment in vitro. • EPOR knockdown impairs proliferation of ERa positive breast cancer cells. • EPOR knockdown reduces AKT phosphorylation and ERa activity. - Abstract: The main function of Erythropoietin (EPO) and its receptor (EPOR) is the stimulation of erythropoiesis. Recombinant human EPO (rhEPO) is therefore used to treat anemia in cancer patients. However, clinical trials have indicated that rhEPO treatment might promote tumor progression and has a negative effect on patient survival. In addition,more » EPOR expression has been detected in several cancer forms. Using a newly produced anti-EPOR antibody that reliably detects the full-length isoform of the EPOR we show that breast cancer tissue and cells express the EPOR protein. rhEPO stimulation of cultured EPOR expressing breast cancer cells did not result in increased proliferation, overt activation of EPOR (receptor phosphorylation) or a consistent activation of canonical EPOR signaling pathway mediators such as JAK2, STAT3, STAT5, or AKT. However, EPOR knockdown experiments suggested functional EPO receptors in estrogen receptor positive (ERα{sup +}) breast cancer cells, as reduced EPOR expression resulted in decreased proliferation. This effect on proliferation was not seen in ERα negative cells. EPOR knockdown decreased ERα activity further supports a mechanism by which EPOR affects proliferation via ERα-mediated mechanisms. We show that EPOR protein is expressed in breast cancer cells, where it appears to promote proliferation by an EPO-independent mechanism in ERα expressing breast cancer cells.« less

An epigenetically distinct breast cancer cell subpopulation promotes collective invasion

PubMed Central

Westcott, Jill M.; Prechtl, Amanda M.; Maine, Erin A.; Dang, Tuyen T.; Esparza, Matthew A.; Sun, Han; Zhou, Yunyun; Xie, Yang; Pearson, Gray W.

2015-01-01

Tumor cells can engage in a process called collective invasion, in which cohesive groups of cells invade through interstitial tissue. Here, we identified an epigenetically distinct subpopulation of breast tumor cells that have an enhanced capacity to collectively invade. Analysis of spheroid invasion in an organotypic culture system revealed that these “trailblazer” cells are capable of initiating collective invasion and promote non-trailblazer cell invasion, indicating a commensal relationship among subpopulations within heterogenous tumors. Canonical mesenchymal markers were not sufficient to distinguish trailblazer cells from non-trailblazer cells, suggesting that defining the molecular underpinnings of the trailblazer phenotype could reveal collective invasion-specific mechanisms. Functional analysis determined that DOCK10, ITGA11, DAB2, PDFGRA, VASN, PPAP2B, and LPAR1 are highly expressed in trailblazer cells and required to initiate collective invasion, with DOCK10 essential for metastasis. In patients with triple-negative breast cancer, expression of these 7 genes correlated with poor outcome. Together, our results indicate that spontaneous conversion of the epigenetic state in a subpopulation of cells can promote a transition from in situ to invasive growth through induction of a cooperative form of collective invasion and suggest that therapeutic inhibition of trailblazer cell invasion may help prevent metastasis. PMID:25844900

[Breast feeding practice and activities for its promotion in Central America, Panamá and Dominican Republic].

PubMed

García, B; Delgado, H L; Valverde, V; Townsend, J; Fischer, M; Praun, A

1985-06-01

This paper summarizes the data presented by the representatives of Central America, Panama and the Dominican Republic at the II Regional Seminar on the Promotion of Breast-Feeding, held in Isla Contadora, Panama, April 25-29, 1983. The representatives of Costa Rica, Honduras and Panama provided up-to-date, representative data in regard to the breast-feeding practice. The average weaning age in the urban and rural areas of Costa Rica is 6 and 4 months, respectively. In Honduras and Panama, 43 and 17% of the infants from urban areas, and 21 and 37% of the babies from rural areas, respectively, were weaned before they reached four months of age. The need for availability of permanent systems to collect information on the breast-feeding practice in the different countries is pointed out. With regard to promotion actions, the absence of a national policy in favor of breast-feeding is evident. Moreover, in the national education systems, little importance is given to the subject. On the other hand, the advances achieved by some hospitals in favoring breast-feeding are mentioned. These include rooming in, the feeding of colostrum to newborns, and the establishment of human milk banks to feed premature babies whose mothers are unable to breast-feed them. Another acknowledged fact is that in the rural areas the agricultural home educators do not reinforce the breast-feeding practice. Also, there is a lack of information on the fulfillment of laws instituted for the protection of pregnant and lactating mothers, as far as pre and postnatal rest is concerned.

Factors influencing diagnosis delay of advanced breast cancer in Moroccan women.

PubMed

Maghous, A; Rais, F; Ahid, S; Benhmidou, N; Bellahamou, K; Loughlimi, H; Marnouche, E; Elmajjaoui, S; Elkacemi, H; Kebdani, T; Benjaafar, N

2016-06-07

several factors and with advanced stages. There is a need for improving breast cancer information in our populations and training of general practitioners to reduce advanced breast cancer by promoting early detection.

Percent Mammographic Density and Dense Area as Risk Factors for Breast Cancer.

PubMed

Rauh, C; Hack, C C; Häberle, L; Hein, A; Engel, A; Schrauder, M G; Fasching, P A; Jud, S M; Ekici, A B; Loehberg, C R; Meier-Meitinger, M; Ozan, S; Schulz-Wendtland, R; Uder, M; Hartmann, A; Wachter, D L; Beckmann, M W; Heusinger, K

2012-08-01

Purpose: Mammographic characteristics are known to be correlated to breast cancer risk. Percent mammographic density (PMD), as assessed by computer-assisted methods, is an established risk factor for breast cancer. Along with this assessment the absolute dense area (DA) of the breast is reported as well. Aim of this study was to assess the predictive value of DA concerning breast cancer risk in addition to other risk factors and in addition to PMD. Methods: We conducted a case control study with hospital-based patients with a diagnosis of invasive breast cancer and healthy women as controls. A total of 561 patients and 376 controls with available mammographic density were included into this study. We describe the differences concerning the common risk factors BMI, parital status, use of hormone replacement therapy (HRT) and menopause between cases and controls and estimate the odds ratios for PMD and DA, adjusted for the mentioned risk factors. Furthermore we compare the prediction models with each other to find out whether the addition of DA improves the model. Results: Mammographic density and DA were highly correlated with each other. Both variables were as well correlated to the commonly known risk factors with an expected direction and strength, however PMD (ρ = -0.56) was stronger correlated to BMI than DA (ρ = -0.11). The group of women within the highest quartil of PMD had an OR of 2.12 (95 % CI: 1.25-3.62). This could not be seen for the fourth quartile concerning DA. However the assessment of breast cancer risk could be improved by including DA in a prediction model in addition to common risk factors and PMD. Conclusions: The inclusion of the parameter DA into a prediction model for breast cancer in addition to established risk factors and PMD could improve the breast cancer risk assessment. As DA is measured together with PMD in the process of computer-assisted assessment of PMD it might be considered to include it as one additional breast

Roles of Biopsychosocial Factors in the Development of Breast Cancer

PubMed Central

Özkan, Mine; Yıldırım, Nazmiye; Dişçi, Rian; İlgün, Ahmet Serkan; Sarsenov, Dauren; Alço, Gül; Aktepe, Fatma; Kalyoncu, Nesiba; İzci, Filiz; Selamoğlu, Derya; Ordu, Çetin; Pilancı, Kezban Nur; Erdoğan, Zeynep İyigün; Eralp, Yeşim; Özmen, Vahit

2017-01-01

Objective The aim of this study was to determine the roles of biopsychosocial risk factors in the development of breast cancer. Materials and methods This hospital-based case-control study included 491 women with breast cancer (study group) and 512 women who did not have cancer or other serious diseases (control group). Biological, psychological, and social risk factors were compared between the two groups. Data were collected using the semi-structured interview, the Stress Assessment Form, and the Coping Strategy Indicator to assess these factors. Results When the significantly different biopsychosocial variables between the study and the control groups were evaluated together, independent breast cancer risk factors were found as follows: a stressor experienced in the last 5 years, age 40 years and older, inadequate social support perception, use of avoidance coping strategy, being a housewife, having a family history of cancer, and having a body mass index ≥25. Conclusion This study showed a relationship between breast cancer risk and manageable variables (obesity, stressor and coping strategy, social support, and employment status), age and family history of cancer, which are biopsychosocial factors. Biopsychosocial aspects are becoming a greater part of many different healthcare systems. PMID:29082379

CD147, CD44, and the epidermal growth factor receptor (EGFR) signaling pathway cooperate to regulate breast epithelial cell invasiveness.

PubMed

Grass, G Daniel; Tolliver, Lauren B; Bratoeva, Momka; Toole, Bryan P

2013-09-06

The immunoglobulin superfamily glycoprotein CD147 (emmprin; basigin) is associated with an invasive phenotype in various types of cancers, including malignant breast cancer. We showed recently that up-regulation of CD147 in non-transformed, non-invasive breast epithelial cells is sufficient to induce an invasive phenotype characterized by membrane type-1 matrix metalloproteinase (MT1-MMP)-dependent invadopodia activity (Grass, G. D., Bratoeva, M., and Toole, B. P. (2012) Regulation of invadopodia formation and activity by CD147. J. Cell Sci. 125, 777-788). Here we found that CD147 induces breast epithelial cell invasiveness by promoting epidermal growth factor receptor (EGFR)-Ras-ERK signaling in a manner dependent on hyaluronan-CD44 interaction. Furthermore, CD147 promotes assembly of signaling complexes containing CD147, CD44, and EGFR in lipid raftlike domains. We also found that oncogenic Ras regulates CD147 expression, hyaluronan synthesis, and formation of CD147-CD44-EGFR complexes, thus forming a positive feedback loop that may amplify invasiveness. Last, we showed that malignant breast cancer cells are heterogeneous in their expression of surface-associated CD147 and that high levels of membrane CD147 correlate with cell surface EGFR and CD44 levels, activated EGFR and ERK1, and activated invadopodia. Future studies should evaluate CD147 as a potential therapeutic target and disease stratification marker in breast cancer.

CD147, CD44, and the Epidermal Growth Factor Receptor (EGFR) Signaling Pathway Cooperate to Regulate Breast Epithelial Cell Invasiveness*

PubMed Central

Grass, G. Daniel; Tolliver, Lauren B.; Bratoeva, Momka; Toole, Bryan P.

2013-01-01

The immunoglobulin superfamily glycoprotein CD147 (emmprin; basigin) is associated with an invasive phenotype in various types of cancers, including malignant breast cancer. We showed recently that up-regulation of CD147 in non-transformed, non-invasive breast epithelial cells is sufficient to induce an invasive phenotype characterized by membrane type-1 matrix metalloproteinase (MT1-MMP)-dependent invadopodia activity (Grass, G. D., Bratoeva, M., and Toole, B. P. (2012) Regulation of invadopodia formation and activity by CD147. J. Cell Sci. 125, 777–788). Here we found that CD147 induces breast epithelial cell invasiveness by promoting epidermal growth factor receptor (EGFR)-Ras-ERK signaling in a manner dependent on hyaluronan-CD44 interaction. Furthermore, CD147 promotes assembly of signaling complexes containing CD147, CD44, and EGFR in lipid raftlike domains. We also found that oncogenic Ras regulates CD147 expression, hyaluronan synthesis, and formation of CD147-CD44-EGFR complexes, thus forming a positive feedback loop that may amplify invasiveness. Last, we showed that malignant breast cancer cells are heterogeneous in their expression of surface-associated CD147 and that high levels of membrane CD147 correlate with cell surface EGFR and CD44 levels, activated EGFR and ERK1, and activated invadopodia. Future studies should evaluate CD147 as a potential therapeutic target and disease stratification marker in breast cancer. PMID:23888049

Short-Form Ron Promotes Spontaneous Breast Cancer Metastasis through Interaction with Phosphoinositide 3-Kinase

PubMed Central

Liu, Xuemei; Zhao, Ling; DeRose, Yoko S.; Lin, Yi-Chun; Bieniasz, Magdalena; Eyob, Henok; Buys, Saundra S.; Neumayer, Leigh

2011-01-01

Receptor tyrosine kinases (RTKs) have been the subject of intense investigation due to their widespread deregulation in cancer and the prospect of developing targeted therapeutics against these proteins. The Ron RTK has been implicated in tumor aggressiveness and is a developing target for therapy, but its function in tumor progression and metastasis is not fully understood. We examined Ron activity in human breast cancers and found striking predominance of an activated Ron isoform known as short-form Ron (sfRon), whose function in breast tumors has not been explored. We found that sfRon plays a significant role in aggressiveness of breast cancer in vitro and in vivo. sfRon expression was sufficient to convert slow-growing, nonmetastatic tumors into rapidly growing tumors that spontaneously metastasized to liver and bones. Mechanistic studies revealed that sfRon promotes epithelial-mesenchymal transition, invasion, tumor growth, and metastasis through interaction with p85, the regulatory subunit of phosphoinositide 3-kinase (PI3K). Inhibition of PI3K activity, or introduction of a single mutation in the p85 docking site on sfRon, completely eliminated the ability of sfRon to promote tumor growth, invasion, and metastasis. These findings reveal sfRon as an important new player in breast cancer and validate Ron and PI3K as therapeutic targets in this disease. PMID:22207901

Increased expression of CYP4Z1 promotes tumor angiogenesis and growth in human breast cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yu, Wei; Chai, Hongyan; Li, Ying

2012-10-01

Cytochrome P450 (CYP) 4Z1, a novel CYP4 family member, is over-expressed in human mammary carcinoma and associated with high-grade tumors and poor prognosis. However, the precise role of CYP4Z1 in tumor progression is unknown. Here, we demonstrate that CYP4Z1 overexpression promotes tumor angiogenesis and growth in breast cancer. Stable expression of CYP4Z1 in T47D and BT-474 human breast cancer cells significantly increased mRNA expression and production of vascular endothelial growth factor (VEGF)-A, and decreased mRNA levels and secretion of tissue inhibitor of metalloproteinase-2 (TIMP-2), without affecting cell proliferation and anchorage-independent cell growth in vitro. Notably, the conditioned medium from CYP4Z1-expressingmore » cells enhanced proliferation, migration and tube formation of human umbilical vein endothelial cells, and promoted angiogenesis in the zebrafish embryo and chorioallantoic membrane of the chick embryo. In addition, there were lower levels of myristic acid and lauric acid, and higher contents of 20-hydroxyeicosatetraenoic acid (20-HETE) in CYP4Z1-expressing T47D cells compared with vector control. CYP4Z1 overexpression significantly increased tumor weight and microvessel density by 2.6-fold and 1.9-fold in human tumor xenograft models, respectively. Moreover, CYP4Z1 transfection increased the phosphorylation of ERK1/2 and PI3K/Akt, while PI3K or ERK inhibitors and siRNA silencing reversed CYP4Z1-mediated changes in VEGF-A and TIMP-2 expression. Conversely, HET0016, an inhibitor of the CYP4 family, potently inhibited the tumor-induced angiogenesis with associated changes in the intracellular levels of myristic acid, lauric acid and 20-HETE. Collectively, these data suggest that increased CYP4Z1 expression promotes tumor angiogenesis and growth in breast cancer partly via PI3K/Akt and ERK1/2 activation. -- Highlights: ► CYP4Z1 overexpression promotes human breast cancer growth and angiogenesis. ► The pro-angiogenic effects of CYP

Urban-Rural Disparity of Breast Cancer and Socioeconomic Risk Factors in China

PubMed Central

Fei, Xufeng; Wu, Jiaping; Kong, Zhe; Christakos, George

2015-01-01

Breast cancer is one of the most commonly diagnosed cancers worldwide. The primary aim of this work is the study of breast cancer disparity among Chinese women in urban vs. rural regions and its associations with socioeconomic factors. Data on breast cancer incidence were obtained from the Chinese cancer registry annual report (2005–2009). The ten socioeconomic factors considered in this study were obtained from the national population 2000 census and the Chinese city/county statistical yearbooks. Student’s T test was used to assess disparities of female breast cancer and socioeconomic factors in urban vs. rural regions. Pearson correlation and ordinary least squares (OLS) models were employed to analyze the relationships between socioeconomic factors and cancer incidence. It was found that the breast cancer incidence was significantly higher in urban than in rural regions. Moreover, in urban regions, breast cancer incidence remained relatively stable, whereas in rural regions it displayed an annual percentage change (APC) of 8.55. Among the various socioeconomic factors considered, breast cancer incidence exhibited higher positive correlations with population density, percentage of non-agriculture population, and second industry output. On the other hand, the incidence was negatively correlated with the percentage of population employed in primary industry. Overall, it was observed that higher socioeconomic status would lead to a higher breast cancer incidence in China. When studying breast cancer etiology, special attention should be paid to environmental pollutants, especially endocrine disruptors produced during industrial activities. Lastly, the present work’s findings strongly recommend giving high priority to the development of a systematic nationwide breast cancer screening program for women in China; with sufficient participation, mammography screening can considerably reduce mortality among women. PMID:25688556

Antiphospholipid antibodies promote tissue factor-dependent angiogenic switch and tumor progression.

PubMed

Wu, Yuan-Yuan; V Nguyen, Andrew; Wu, Xiao-Xuan; Loh, Mingyu; Vu, Michelle; Zou, Yiyu; Liu, Qiang; Guo, Peng; Wang, Yanhua; Montgomery, Leslie L; Orlofsky, Amos; Rand, Jacob H; Lin, Elaine Y

2014-12-01

Progression to an angiogenic state is a critical event in tumor development, yet few patient characteristics have been identified that can be mechanistically linked to this transition. Antiphospholipid autoantibodies (aPLs) are prevalent in many human cancers and can elicit proangiogenic expression in several cell types, but their role in tumor biology is unknown. Herein, we observed that the elevation of circulating aPLs among breast cancer patients is specifically associated with invasive-stage tumors. By using multiple in vivo models of breast cancer, we demonstrated that aPL-positive IgG from patients with autoimmune disease rapidly accelerates tumor angiogenesis and consequent tumor progression, particularly in slow-growing avascular tumors. The action of aPLs was local to the tumor site and elicited leukocytic infiltration and tumor invasion. Tumor cells treated with aPL-positive IgG expressed multiple proangiogenic genes, including vascular endothelial growth factor, tissue factor (TF), and colony-stimulating factor 1. Knockdown and neutralization studies demonstrated that the effects of aPLs on tumor angiogenesis and growth were dependent on tumor cell-derived TF. Tumor-derived TF was essential for the development of pericyte coverage of tumor microvessels and aPL-induced tumor cell expression of chemokine ligand 2, a mediator of pericyte recruitment. These findings identify antiphospholipid autoantibodies as a potential patient-specific host factor promoting the transition of indolent tumors to an angiogenic malignant state through a TF-mediated pathogenic mechanism. Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Histone H1 and Chromosomal Protein HMGN2 Regulate Prolactin-induced STAT5 Transcription Factor Recruitment and Function in Breast Cancer Cells*

PubMed Central

Schauwecker, Suzanne M.; Kim, J. Julie; Licht, Jonathan D.; Clevenger, Charles V.

2017-01-01

The hormone prolactin (PRL) contributes to breast cancer pathogenesis through various signaling pathways, one of the most notable being the JAK2/signal transducer and activator of transcription 5 (STAT5) pathway. PRL-induced activation of the transcription factor STAT5 results in the up-regulation of numerous genes implicated in breast cancer pathogenesis. However, the molecular mechanisms that enable STAT5 to access the promoters of these genes are not well understood. Here, we show that PRL signaling induces chromatin decompaction at promoter DNA, corresponding with STAT5 binding. The chromatin-modifying protein high mobility group nucleosomal binding domain 2 (HMGN2) specifically promotes STAT5 accessibility at promoter DNA by facilitating the dissociation of the linker histone H1 in response to PRL. Knockdown of H1 rescues the decrease in PRL-induced transcription following HMGN2 knockdown, and it does so by allowing increased STAT5 recruitment. Moreover, H1 and STAT5 are shown to function antagonistically in regulating PRL-induced transcription as well as breast cancer cell biology. While reduced STAT5 activation results in decreased PRL-induced transcription and cell proliferation, knockdown of H1 rescues both of these effects. Taken together, we elucidate a novel mechanism whereby the linker histone H1 prevents STAT5 binding at promoter DNA, and the PRL-induced dissociation of H1 mediated by HMGN2 is necessary to allow full STAT5 recruitment and promote the biological effects of PRL signaling. PMID:28035005

Relative expression of rRNA transcripts and 45S rDNA promoter methylation status are dysregulated in tumors in comparison with matched-normal tissues in breast cancer.

PubMed

Karahan, Gurbet; Sayar, Nilufer; Gozum, Gokcen; Bozkurt, Betul; Konu, Ozlen; Yulug, Isik G

2015-06-01

Ribosomal RNA (rRNA) expression, one of the most important factors regulating ribosome production, is primarily controlled by a CG-rich 45 S rDNA promoter. However, the DNA methylation state of the 45 S rDNA promoter, as well as its effect on rRNA gene expression in types of human cancers is controversial. In the present study we analyzed the methylation status of the rDNA promoter (-380 to +53 bp) as well as associated rRNA expression levels in breast cancer cell lines and breast tumor-normal tissue pairs. We found that the aforementioned regulatory region was extensively methylated (74-96%) in all cell lines and in 68% (13/19 tumor-normal pairs) of the tumors. Expression levels of rRNA transcripts 18 S, 28 S, 5.8 S and 45 S external transcribed spacer (45 S ETS) greatly varied in the breast cancer cell lines regardless of their methylation status. Analyses of rRNA transcript expression levels in the breast tumor and normal matched tissues showed no significant difference when normalized with TBP. On the other hand, using the geometric mean of the rRNA expression values (GM-rRNA) as reference enabled us to identify significant changes in the relative expression of rRNAs in the tissue samples. We propose GM-rRNA normalization as a novel strategy to analyze expression differences between rRNA transcripts. Accordingly, the 18S rRNA/GM-rRNA ratio was significantly higher whereas the 5.8S rRNA/GM-rRNA ratio was significantly lower in breast tumor samples than this ratio in the matched normal samples. Moreover, the 18S rRNA/GM-rRNA ratio was negatively correlated with the 45 S rDNA promoter methylation level in the normal breast tissue samples, yet not in the breast tumors. Significant correlations observed between the expression levels of rRNA transcripts in the normal samples were lost in the tumor samples. We showed that the expression of rRNA transcripts may not be based solely on promoter methylation. Carcinogenesis may cause dysregulation of the correlation

17beta-estradiol promotes breast cancer cell proliferation-inducing stromal cell-derived factor-1-mediated epidermal growth factor receptor transactivation: reversal by gefitinib pretreatment.

PubMed

Pattarozzi, Alessandra; Gatti, Monica; Barbieri, Federica; Würth, Roberto; Porcile, Carola; Lunardi, Gianluigi; Ratto, Alessandra; Favoni, Roberto; Bajetto, Adriana; Ferrari, Angelo; Florio, Tullio

2008-01-01

The coordinated activity of estrogens and epidermal growth factor receptor (EGFR) family agonists represents the main determinant of breast cancer cell proliferation. Stromal cell-derived factor-1 (SDF-1) enhances extracellular signal-regulated kinases 1 and 2 (ERK1/2) activity via the transactivation of EGFR and 17beta-estradiol (E2) induces SDF-1 production to exert autocrine proliferative effects. On this basis, we evaluated whether the inhibition of the tyrosine kinase (TK) activity of EGFR may control different mitogenic stimuli in breast tumors using the EGFR-TK inhibitor gefitinib to antagonize the proliferation induced by E2 in T47D human breast cancer cells. EGF, E2, and SDF-1 induced a dose-dependent T47D cell proliferation, that being nonadditive suggested the activation of common intracellular pathways. Gefitinib treatment inhibited not only the EGF-dependent proliferation and ERK1/2 activation but also the effects of SDF-1 and E2, suggesting that these activities were mediated by EGFR transactivation. Indeed, both SDF-1 and E2 caused EGFR tyrosine phosphorylation. The molecular link between E2 and SDF-1 proliferative effects was identified because 1,1'-(1,4-phenylenebis(methylene))-bis-1,4,8,11-tetraazacyclotetradecane octahydrochloride (AMD3100), a CXCR4 antagonist, inhibited SDF-1- and E2-dependent proliferation and EGFR and ERK1/2 phosphorylation. EGFR transactivation was dependent on c-Src activation. E2 treatment caused a powerful SDF-1 release from T47D cells. Finally, in SKBR3, E2-resistant cells, EGFR was constitutively activated, and AMD3100 reduced EGFR phosphorylation and cell proliferation, whereas HER2-neu was transactivated by SDF-1 in SKBR3 but not in T47D cells. In conclusion, we show that activation of CXCR4 transduces proliferative signals from the E2 receptor to EGFR, whose inhibition is able to revert breast cancer cell proliferation induced by multiple receptor activation.

CYP17 genetic polymorphism, breast cancer, and breast cancer risk factors.

PubMed

Ambrosone, Christine B; Moysich, Kirsten B; Furberg, Helena; Freudenheim, Jo L; Bowman, Elise D; Ahmed, Sabrina; Graham, Saxon; Vena, John E; Shields, Peter G

2003-01-01

Findings from previous studies regarding the association between the CYP17 genotype and breast cancer are inconsistent. We investigated the role of the MspAI genetic polymorphism in the 5' region of CYP17 on risk of breast cancer and as a modifier of reproductive risk factors. Questionnaire and genotyping data were obtained from a population-based, case-control study of premenopausal (n = 182) and postmenopausal (n = 214) European-American Caucasian women in western New York. Cases and controls were frequency matched by age and by county of residence. Odds ratios and 95% confidence intervals were used to estimate relative risks. The CYP17 genotype was not associated with breast cancer risk; however, controls with the A2/A2 genotype (associated with higher estrogens) had earlier menarche and earlier first full-term pregnancy. Premenopausal women with A1/A1 genotypes, but not with A2 alleles, were at significantly decreased risk with late age at menarche (odds ratio = 0.37, 95% confidence interval = 0.14-0.99), and at increased risk with late age at first full-term pregnancy (odds ratio = 4.30, 95% confidence interval = 1.46-12.67) and with use of oral contraceptives (odds ratio = 3.24, 95% confidence interval = 1.08-9.73). Associations were weaker among postmenopausal women. These results suggest that the effects of factors that may alter breast cancer risk through a hormonal mechanism may be less important among premenopausal women with putative higher lifetime exposures to circulating estrogens related to the CYP17 A2 allele.

Insulin like growth factor 2 regulation of aryl hydrocarbon receptor in MCF-7 breast cancer cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tomblin, Justin K.; Salisbury, Travis B., E-mail: salisburyt@marshall.edu

2014-01-17

Highlights: •IGF-2 stimulates concurrent increases in AHR and CCND1 expression. •IGF-2 promotes the binding of AHR to the endogenous cyclin D1 promoter. •AHR knockdown inhibits IGF-2 stimulated increases in CCND1 mRNA and protein. •AHR knockdown inhibits IGF-2 stimulated increases in MCF-7 proliferation. -- Abstract: Insulin like growth factor (IGF)-1 and IGF-2 stimulate normal growth, development and breast cancer cell proliferation. Cyclin D1 (CCND1) promotes cell cycle by inhibiting retinoblastoma protein (RB1). The aryl hydrocarbon receptor (AHR) is a major xenobiotic receptor that also regulates cell cycle. The purpose of this study was to investigate whether IGF-2 promotes MCF-7 breast cancermore » proliferation by inducing AHR. Western blot and quantitative real time PCR (Q-PCR) analysis revealed that IGF-2 induced an approximately 2-fold increase (P < .001) in the expression of AHR and CCND1. Chromatin immunoprecipitation (ChIP), followed by Q-PCR indicated that IGF-2 promoted (P < .001) a 7-fold increase in AHR binding on the CCND1 promoter. AHR knockdown significantly (P < .001) inhibited IGF-2 stimulated increases in CCND1 mRNA and protein. AHR knockdown cells were less (P < .001) responsive to the proliferative effects of IGF-2 than control cells. Collectively, our findings have revealed a new regulatory mechanism by which IGF-2 induction of AHR promotes the expression of CCND1 and the proliferation of MCF-7 cells. This previously uncharacterized pathway could be important for the proliferation of IGF responsive cancer cells that also express AHR.« less

Risk factors for benign breast disease: a 30-year cohort study.

PubMed Central

Hislop, T G; Elwood, J M

1981-01-01

Data on the menstrual history, family history and degree of obesity of 1374 Vancouver nursing students were collected in 1945 and from 1947 to 1956. In 1979, 768 of these women were located; 726 (94%) responded and participated in a follow-up study, providing information on their subsequent medical history and on breast-related problems. No major differences were found between the early histories of these participants and those who were not located or did not respond. Among the respondents 215 gave a history of symptoms compatible with benign breast disease; in 107 this diagnosis was confirmed by biopsy. By age 50 the cumulative risk for benign breast disease was 17% for biopsied and 31% for symptomatic disease. Biopsied benign breast disease was associated with premenstrual breast discomfort, irregular menses, a history of abortions, a family history of both benign and malignant breast disease, lack of use of oral contraceptives, a low index of obesity and small breasts, obesity and breast size being independent. Factors associated with symptomatic benign breast disease were usually associated with a greater likelihood of biopsy for symptomatic disease; hence, the relative risks for biopsied disease were generally greater than those for symptomatic disease. Although the risk factors for benign breast disease differ from those for breast cancer, the findings are consistent with the hypothesis of excessive circulating estrogen. PMID:7459788

The Interaction Between Genetic Ancestry and Breast Cancer Risk Factors among Hispanic women: The Breast Cancer Health Disparities Study

PubMed Central

Hines, Lisa M.; Sedjo, Rebecca L.; Byers, Tim; John, Esther M.; Fejerman, Laura; Stern, Mariana C.; Baumgartner, Kathy B.; Giuliano, Anna R.; Torres-Mejia, Gabriela; Wolff, Roger K.; Harrall, Kylie K.; Slattery, Martha L.

2016-01-01

Background Hispanic women have lower breast cancer incidence rates than non-Hispanic white (NHW) women. To what extent genetic versus non-genetic factors account for this difference is unknown. Methods Using logistic regression, we evaluated the interactive influences of established risk factors and ethnicity (self-identified and identified by ancestral informative markers) on breast cancer risk among 2326 Hispanic and 1854 NHW postmenopausal women from the US and Mexico in the Breast Cancer Health Disparities Study. Results The inverse association between % Native American(NA) ancestry and breast cancer risk was only slightly attenuated after adjusting for known risk factors [lowest versus highest quartile: odds ratio(OR)=1.39, 95% confidence interval(CI)=1.00–1.92 among US Hispanics; OR=1.92 (1.29–2.86) among Mexican women]. The prevalence of several risk factors, as well as the associations with certain factors and breast cancer risk, differed according to genetic admixture. For example, higher BMI was associated with reduced risk among women with lower NA ancestry only [BMI <25 versus >30: OR=0.65 (0.44–0.98) among US Hispanics; OR=0.53 (0.29–0.97) among Mexicans]. The average number of risk factors among cases was inversely related to % NA ancestry. Conclusions The lower NA ancestry groups were more likely to have the established risk factors, with the exception of BMI. While the majority of factors were associated with risk in the expected directions among all women, BMI had an inverse association among Hispanics with lower NA ancestry. Impact These data suggest that the established risk factors are less relevant for breast cancer development among women with more NA ancestry. PMID:27932594

Downregulation of FOXP2 promotes breast cancer migration and invasion through TGFβ/SMAD signaling pathway.

PubMed

Chen, Meng-Ting; Sun, He-Fen; Li, Liang-Dong; Zhao, Yang; Yang, Li-Peng; Gao, Shui-Ping; Jin, Wei

2018-06-01

Cancer metastasis and relapse are the primary cause of mortality for patients with breast cancer. The present study performed quantitative proteomic analysis on the differentially expressed proteins between highly metastatic breast cancer cells and parental cells. It was revealed that forkhead box P2 (FOXP2), a transcription factor in neural development, may become a potential inhibitor of breast cancer metastasis. The results demonstrated that patients with a lower level of FOXP2 expression had significantly poorer relapse-free survival (P=0.0047). The transcription of FOXP2 was also significantly downregulated in breast cancer tissue compared with normal breast tissue (P=0.0005). In addition, FOXP2 may inhibit breast cancer cell migration and invasion in vitro . It was also revealed that the underlying mechanism may include the epithelial-mesenchymal transition process driven by the tumor growth factor β/SMAD signaling pathway. In conclusion, the present study identified FOXP2 as a novel suppressor and prognostic marker of breast cancer metastasis. These results may provide further insight into breast cancer prevention and the development of novel treatments.

Teaching and breast self-examination: an insufficiency of instruction.

PubMed

Turnbull, Beverley J; Roberts, Kathryn

2004-01-01

Client teaching is recognised as an essential component of nursing and midwifery care, and all clinical areas provide opportunities for informal client teaching. This qualitative study aimed to explore registered nurses' professional practices with regard to teaching breast self-examination (BSE), and to identify factors that influenced their participation or non-participation in teaching about breast health. Participants' views were obtained using individual semi-structured interviews. The data were analysed inductively, that is, without imposing structure from the interview questions. Findings revealed that participants' perspectives of BSE and breast health, the dual symbolism of breasts, and the time constraints of clinical practice, were significant factors that impacted on participants' personal BSE practices and on their level of participation in teaching BSE. The results indicate that that nurses and midwives do not view teaching breast health as part of their role in client interaction, particularly in an acute care setting. Although nursing literature identifies midwives and nurses as ideally placed to promote health promotion activities, the image of BSE as linked to breast cancer, the dominant illness oriented model of care and a task orientated culture in health care facilities do not facilitate this.

Epidemiological correlates of breast cancer in South India.

PubMed

Babu, Giridhara Rathnaiah; Lakshmi, Srikanthi Bodapati; Thiyagarajan, Jotheeswaran Amuthavalli

2013-01-01

Breast cancer is the most frequent cancer in women globally and represents the second leading cause of cancer death among women (after lung cancer). India is going through epidemiologic transition. It is reported that the incidence of breast cancer is rising rapidly as a result of changes in reproductive risk factors, dietary habits and increasing life expectancy, acting in concert with genetic factors. In order to understand the existing epidemiological correlates of breast cancer in South India, a systematic review of evidence available on epidemiologic correlates of breast cancer addressing incidence, prevalence, and associated factors like age, reproductive factors, cultural and religious factors was performed with specific focus on screening procedures in southern India. An increase in breast cancer incidence due to various modifiable risk factors was noted, especially in women over 40 years of age, with late stage of presentation, lack of awareness about screening, costs, fear and stigma associated with the disease serving as major barriers for early presentation. Educational strategies should be aimed at modifying the life style, early planning of pregnancy, promoting breast feeding and physical activity. It is very important to obtain reliable data for planning policies, decision-making and setting up the priorities.

Insufficient Knowledge of Breast Cancer Risk Factors Among Malaysian Female University Students

PubMed Central

Samah, Asnarulkhadi Abu; Ahmadian, Maryam; Latiff, Latiffah A.

2016-01-01

Background: Despite continuous argument about the efficacy of breast self-examination; it still could be a life-saving technique through inspiring and empowering women to take better control over their body/breast and health. This study investigated Malaysian female university students’ knowledge about breast cancer risk factors, signs, and symptoms and assessed breast self-examination frequency among students. Method: A cross-sectional survey was conducted in 2013 in nine public and private universities in the Klang Valley and Selangor. 842 female students were respondents for the self-administered survey technique. Simple descriptive and inferential statistics were employed for data analysis. Results: The uptake of breast self-examination (BSE) was less than 50% among the students. Most of students had insufficient knowledge on several breast cancer risk factors. Conclusion: Actions and efforts should be done to increase knowledge of breast cancer through the development of ethnically and traditionally sensitive educational training on BSE and breast cancer literacy. PMID:26234996

Mode of detection: an independent prognostic factor for women with breast cancer.

PubMed

Hofvind, Solveig; Holen, Åsne; Román, Marta; Sebuødegård, Sofie; Puig-Vives, Montse; Akslen, Lars

2016-06-01

To investigate breast cancer survival and risk of breast cancer death by detection mode (screen-detected, interval, and detected outside the screening programme), adjusting for prognostic and predictive tumour characteristics. Information about detection mode, prognostic (age, tumour size, histologic grade, lymph node status) and predictive factors (molecular subtypes based on immunohistochemical analyses of hormone receptor status (estrogen and progesterone) and Her2 status) were available for 8344 women in Norway aged 50-69 at diagnosis of breast cancer, 2005-2011. A total of 255 breast cancer deaths were registered by the end of 2011. Kaplan-Meier method was used to estimate six years breast cancer specific survival and Cox proportional hazard model to estimate hazard ratio (HR) for breast cancer death by detection mode, adjusting for prognostic and predictive factors. Women with screen-detected cancer had favourable prognostic and predictive tumour characteristics compared with interval cancers and those detected outside the screening programme. The favourable characteristics were present for screen-detected cancers, also within the subtypes. Adjusted HR of dying from breast cancer was two times higher for women with symptomatic breast cancer (interval or outside the screening), using screen-detected tumours as the reference. Detection mode is an independent prognostic factor for women diagnosed with breast cancer. Information on detection mode might be relevant for patient management to avoid overtreatment. © The Author(s) 2015.

Understanding the factors that influence breast reconstruction decision making in Australian women.

PubMed

Somogyi, Ron Barry; Webb, Angela; Baghdikian, Nairy; Stephenson, John; Edward, Karen-Leigh; Morrison, Wayne

2015-04-01

Breast reconstruction is safe and improves quality of life. Despite this, many women do not undergo breast reconstruction and the reasons for this are poorly understood. This study aims to identify the factors that influence a woman's decision whether or not to have breast reconstruction and to better understand their attitudes toward reconstruction. An online survey was distributed to breast cancer patients from Breast Cancer Network Australia. Results were tabulated, described qualitatively and analyzed for significance using a multiple logistic regression model. 501 mastectomy patients completed surveys, of which 62% had undergone breast reconstruction. Factors that positively influenced likelihood of reconstruction included lower age, bilateral mastectomy, access to private hospitals, decreased home/work responsibilities, increased level of home support and early discussion of reconstructive options. Most common reasons for avoiding reconstruction included "I don't feel the need" and "I don't want more surgery". The most commonly sited sources of reconstruction information came from the breast surgeon followed by the plastic surgeon then the breast cancer nurse and the most influential of these was the plastic surgeon. A model using factors easily obtained on clinical history can be used to understand likelihood of reconstruction. This knowledge may help identify barriers to reconstruction, ultimately improving the clinicians' ability to appropriately educate mastectomy patients and ensure effective decision making around breast reconstruction. Copyright © 2014 Elsevier Ltd. All rights reserved.

Promoting effects of adipose-derived stem cells on breast cancer cells are reversed by radiation therapy.

PubMed

Baaße, Annemarie; Juerß, Dajana; Reape, Elaine; Manda, Katrin; Hildebrandt, Guido

2018-04-01

Partial breast irradiation of early breast cancer patients after lumpectomy and the use of endogenous adipose tissue (AT) for breast reconstruction are promising applications to reduce the side effects of breast cancer therapy. This study tries to investigate the possible risks associated with these therapeutic approaches. It also examines the influence of adipose derived stem cells (ADSCs) as part of the breast cancer microenvironment, and endogenous AT on breast cancer cells following radiation therapy. ADSCs, isolated from human reduction mammoplasties of healthy female donors, exhibited multilineage capacity and specific surface markers. The promoting effects of ADSCs on the growth and survival fraction of breast cancer cells were reversed by treatment with high (8 Gy) or medium (2 Gy) radiation doses. In addition, a suppressing influence on breast cancer growth could be detected by co-culturing with irradiated ADSCs (8 Gy). Furthermore the clonogenic survival of unirradiated tumor cells was reduced by medium of irradiated ADSCs. In conclusion, radiation therapy changed the interactions of ADSCs and breast cancer cells. On the basis of our work, the importance of further studies to exclude potential risks of ADSCs in regenerative applications and radiotherapy has been emphasized.

Risk factors for breast cancer in nulliparous women

PubMed Central

Fioretti, F; Tavani, A; Bosetti, C; Vecchia, C La; Negri, E; Barbone, F; Talamini, R; Franceschi, S

1999-01-01

The relation between hormonal and lifestyle factors and breast cancer risk in nulliparae was investigated using data from two case-control studies conducted in Italy between 1983 and 1994. The study included 1041 nulliparae with histologically confirmed incident breast cancer and 1002 nulliparous controls admitted to hospital for a wide range of acute, non-neoplastic, nonhormone-related diseases. In premenopausal nulliparae, there was an inverse relation with age at menarche [odds ratios (OR) 0.45; 95% confidence intervals (CI) 0.24–0.86 for ≥ 15 years vs < 12], while no association emerged in postmenopausal. Breast cancer risk increased with age at menopause, the OR being 1.91 (95% CI 1.26–2.90) for nulliparae reporting age at menopause ≥ 53 years compared with < 45. Abortion was not related to breast cancer risk, the OR being 0.92 for any spontaneous, 0.97 for any induced and 0.77 for ≥ 2 total abortions compared to none. The OR was 1.75 (95% CI 1.03–2.97) for women reporting their first abortion at age ≥ 30 years compared with < 30. Oral contraceptives and hormone replacement therapy in menopause were moderately related to risk. The OR was 2.71 (95% CI 1.85–3.95) in nulliparae with a family history of breast cancer and 1.60 (95% CI 1.20–2.14) in those with a history of benign breast disease. Compared with nulliparae reporting a low physical activity, the OR was 0.79 (95% CI 0.54–1.16) for those reporting intermediate/high activity. Breast cancer risk increased with total energy intake, the OR being 1.65 (95% CI 0.99–2.75) in the highest tertile; beta-carotene was inversely related to risk (OR 0.60, 95% CI 0.38–0.95) for the highest tertile. Thus, most risk factors for breast cancer in nulliparae were similar to those in women generally. © 1999 Cancer Research Campaign PMID:10206315

Implementation of a School-Based Educational Program to Increase Breast Cancer Awareness and Promote Intergenerational Transmission of Knowledge in a Rural Mexican Community.

PubMed

Soto-Perez-de-Celis, Enrique; Smith, David D; Rojo-Castillo, Maria Patricia; Hurria, Arti; Pavas-Vivas, Alba Milena; Gitler-Weingarten, Rina; Mohar, Alejandro; Chavarri-Guerra, Yanin

2017-10-01

Rural women have limited access to breast cancer education, which partially contributes to late diagnosis and treatment. In this pilot study, we tested the feasibility of implementing a school-based breast cancer educational program for adolescents in a rural Mexican community. We hypothesized that the adolescents' knowledge on breast cancer would increase as a result of the program, and that there would be intergenerational transmission of that knowledge to their older female relatives. Female adolescents from a rural middle school received the educational program. The program would be considered feasible and acceptable if more than 75% reported being satisfied with its contents. Changes in knowledge in the students and their relatives were evaluated using baseline and 4 months follow-up questionnaires. One hundred twenty-six students were enrolled. The program was considered acceptable by 96% of the participants. The students' knowledge regarding breast cancer increased significantly from baseline to 4 months follow-up (63% to 82%). One hundred ninety-four female relatives completed the initial knowledge questionnaires. The relatives' knowledge regarding breast cancer showed a significant increase from baseline to 4 months follow-up (55% to 61%). Implementing breast cancer educational programs for adolescents in rural communities is feasible and acceptable. The program increased the adolescents' knowledge on breast cancer, and promoted the intergenerational transmission of that knowledge to their female relatives. Intergenerational transmission of knowledge represents a potential method for providing population-based health awareness education globally. In limited-resource settings, education is a valuable tool for achieving early detection and downstaging of breast cancer. Unfortunately, rural women lack access to educational opportunities and information about breast cancer, which is a factor contributing to late diagnosis and treatment. In this study, we

Fibroblast growth factor 2 regulates bone sialoprotein gene transcription in human breast cancer cells.

PubMed

Li, Zhengyang; Wang, Zhitao; Yang, Li; Li, Xinyue; Sasaki, Yoko; Wang, Shuang; Araki, Shouta; Mezawa, Masaru; Takai, Hideki; Nakayama, Youhei; Ogata, Yorimasa

2010-03-01

Bone sialoprotein (BSP) is a major non-collagenous, extracellular matrix glycoprotein associated with mineralized tissues. Fibroblast growth factor 2 (FGF2) is recognized as a potent mitogen for a variety of mesenchymal cells. FGF2 produced by osteoblasts accumulates in the bone matrix and acts as an autocrine/paracrine regulator of osteoblasts. We previously reported that FGF2 regulates BSP gene transcription through the FGF2 response element (FRE) and activator protein 1 (AP1) binding site overlapping with the glucocorticoid response element in the rat BSP gene promoter. In the present study, FGF2 (10 ng/ml) increased BSP and Runx2 mRNA levels at 6 h in MCF7 human breast cancer cells. Transient transfection analyses were performed using chimeric constructs of the human BSP gene promoter linked to a luciferase reporter gene. Treatment of MCF7 cells with FGF2 (10 ng/ml) increased the luciferase activity of the constructs between -84LUC and -927LUC. Gel mobility shift analyses showed that FGF2 increased the binding of AP1 and CRE2. The CRE2- and AP1-protein complexes were disrupted by antibodies against CREB1, c-Fos, c-Jun, Fra2, p300 and Runx2. These studies demonstrate that FGF2 stimulates BSP transcription in MCF7 human breast cancer cells by targeting the AP1 and CRE2 elements in the human BSP gene promoter.

Breast-feeding Duration: Early Weaning-Do We Sufficiently Consider the Risk Factors?

PubMed

Karall, Daniela; Ndayisaba, Jean-Pierre; Heichlinger, Angelika; Kiechl-Kohlendorfer, Ursula; Stojakovic, Sarah; Leitner, Hermann; Scholl-Bürgi, Sabine

2015-11-01

Breast-feeding is the recommended form of nutrition for the first 6 months. This target is unmet, however, in most industrialized regions. We evaluated aspects of breast-feeding in a cohort of mother-baby dyads. Breast-feeding practices in 555 mother-baby dyads were prospectively studied for 24 months (personal interview at birth and 7 structured telephone interviews). Of the babies, 71.3% were fully breast-fed on discharge from maternity hospitals and 11.9% were partially breast-feed. Median breast-feeding duration was 6.93 (interquartile range 2.57-11.00) months; for full (exclusive) breast-feeding 5.62 (interquartile range 3.12-7.77) months; 61.7% received supplemental feedings during the first days of life. Breast-feeding duration in babies receiving supplemental feedings was significantly shorter (median 5.06 months versus 8.21 months, P < 0.001). At 6 months, 9.4% of the mothers were exclusively and 39.5% partially breast-feeding. Risk factors for early weaning were early supplemental feedings (odds ratio [OR] 2.87, 95% CI 1.65-4.98), perceived milk insufficiency (OR 7.35, 95% CI 3.59-15.07), low breast-feeding self-efficacy (a mother's self-confidence in her ability to adequately feed her baby) (OR 3.42, 95% CI 1.48-7.94), lower maternal age (OR 3.89, 95% CI 1.45-10.46), and lower education level of the mother (OR 7.30, 95% CI 2.93-18.20). The recommended full breast-feeding duration of the first 6 months of life was not reached. Sociodemographic variables and factors directly related to breast-feeding practices play an important role on breast-feeding duration/weaning in our region. Understanding risk factors will provide insights to give better support to mothers and prevent short- and long-term morbidity following early weaning.

Estrogen-related receptor alpha induces the expression of vascular endothelial growth factor in breast cancer cells

PubMed Central

Stein, Rebecca A.; Gaillard, Stéphanie; McDonnell, Donald P.

2009-01-01

Estrogen-related receptor alpha (ERRα) is an orphan member of the nuclear receptor family of transcription factors. In addition to its function as a metabolic regulator, ERRα has been implicated in the growth and progression of several malignancies. In the setting of breast cancer, not only is ERRα a putative negative prognostic factor, but we have recently found that knockdown of its expression retards tumor growth in a xenograft model of this disease. The specific aspects of ERRα function that are responsible for its actions in breast cancer, however, remain unclear. Using the coactivator PGC-1α as a protein ligand to regulate ERRα activity, we analyzed the effects of this receptor on gene expression in the ERα-positive MCF-7 cell line. This analysis led to the identification of a large number of potential ERRα target genes, many of which were subsequently validated in other breast cancer cell lines. Importantly, we demonstrate in this study that activation of ERRα in several different breast cancer cell lines leads to a significant increase in VEGF mRNA expression, an activity that translates into an increase in VEGF protein secretion. The induction of VEGF results from the interaction of ERRα with specific ERR-responsive elements within the VEGF promoter. These findings suggest that ERRα-dependent induction of VEGF may contribute to the overall negative phenotype observed in tumors in which ERRα is expressed and provide validation for its use as a therapeutic target in cancer. PMID:19429439

Granulocyte-Colony Stimulating Factor Receptor, Tissue Factor, and VEGF-R Bound VEGF in Human Breast Cancer In Loco.

PubMed

Wojtukiewicz, Marek Z; Sierko, Ewa; Skalij, Piotr; Kamińska, Magda; Zimnoch, Lech; Brekken, Ralf A; Thorpe, Philip E

2016-01-01

Doxorubicin and docetaxel-based chemotherapy regimens used in breast cancer patients are associated with high risk of febrile neutropenia (FN). Granulocyte colony-stimulating factors (G-CSF) are recommended for both treating and preventing chemotherapy-induced neutropenia. Increased thrombosis incidence in G-CSF treated patients was reported; however, the underlying mechanisms remain unclear. The principal activator of blood coagulation in cancer is tissue factor (TF). It additionally contributes to cancer progression and stimulates angiogenesis. The main proangiogenic factor is vascular endothelial growth factor (VEGF). The aim of the study was to evaluate granulocyte-colony stimulating factor receptor (G-CSFR), tissue factor (TF) expression and vascular endothelial growth factor receptor (VEGF-R) bound VEGF in human breast cancer in loco. G-CSFR, TF and VEGFR bound VEGF (VEGF: VEGFR) were assessed in 28 breast cancer tissue samples. Immunohistochemical (IHC) methodologies according to ABC technique and double staining IHC procedure were employed utilizing antibodies against G-CSFR, TF and VEGF associated with VEGFR (VEGF: VEGFR). Expression of G-CSFR was demonstrated in 20 breast cancer tissue specimens (71%). In 6 cases (21%) the expression was strong (IRS 9-12). Strong expression of TF was observed in all investigated cases (100%). Moreover, expression of VEGF: VEGFR was visualized in cancer cells (IRS 5-8). No presence of G-CSFR, TF or VEGF: VEGFR was detected on healthy breast cells. Double staining IHC studies revealed co-localization of G-CSFR and TF, G-CSFR and VEGF: VEGFR, as well as TF and VEGF: VEGFR on breast cancer cells and ECs. The results of the study indicate that GCSFR, TF and VEGF: VEGFR expression as well as their co-expression might influence breast cancer biology, and may increase thromboembolic adverse events incidence.

Interleukin 2 and interleukin 10 function synergistically to promote CD8+ T cell cytotoxicity, which is suppressed by regulatory T cells in breast cancer.

PubMed

Li, Xiaogang; Lu, Ping; Li, Bo; Zhang, Wanfu; Yang, Rong; Chu, Yan; Luo, Kaiyuan

2017-06-01

The precise role of interleukin (IL)-10 in breast cancer is not clear. Previous studies suggested a tumor-promoting role of IL-10 in breast cancer, whereas recent discoveries that IL-10 activated and expanded tumor-resident CD8 + T cells challenged the traditional view. Here, we investigated the role of IL-10 in HLA-A2-positive breast cancer patients with Grade III, Stage IIA or IIB in-situ and invasive ductal carcinoma, and compared it with that of IL-2, the canonical CD8 + T cell growth factor. We first observed that breast cancer patients presented higher serum levels of IL-2 and IL-10 than healthy controls. Upon prolonged TCR stimulation, peripheral blood CD8 + T cells from breast cancer patients tended to undergo apoptosis, which could be prevented by the addition of IL-2 and/or IL-10. The cytotoxicity of TCR-activated CD8 + T cells was also enhanced by exogenous IL-2 and/or IL-10. Interestingly, IL-2 and IL-10 demonstrated synergistic effects, since the enhancement in CD8 + T cell function when both cytokines were added was greater than the sum of the improvements mediated by each individual cytokine. IL-10 by itself could not promote the proliferation of CD8 + T cells but could significantly enhance IL-2-mediated promotion of CD8 + T cell proliferation. In addition, the cytotoxicity of tumor-infiltrating CD8 + T cells in breast tumor was elevated when both IL-2 and IL-10 were present but not when either one was absent. This synergistic effect was stopped by CD4 + CD25 + regulatory T cells (Treg), which depleted IL-2 in a cell number-dependent manner. Together, these results demonstrated that IL-2 and IL-10 could work synergistically to improve the survival, proliferation, and cytotoxicity of activated CD8 + T cells, an effect suppressible by CD4 + CD25 + Treg cells. Copyright © 2017 Elsevier Ltd. All rights reserved.

Epidemiology, major risk factors and genetic predisposition for breast cancer in the Pakistani population.

PubMed

Shaukat, Uzma; Ismail, Muhammad; Mehmood, Nasir

2013-01-01

Occurrence of breast cancer is related to genetic as well as cultural, environmental and life-style factors. Variations in diversity of these factors among different ethnic groups and geographical areas emphasize the immense need for studies in all racial-ethnic populations. The incidence of breast cancer in Pakistan is highest in Asians after Jews in Israel and 2.5 times higher than that in neighboring countries like Iran and India, accounting for 34.6% of female cancers. The Pakistani population is deficient in information regarding breast cancer etiology and epidemiology, but efforts done so far had suggested consanguinity as a major risk factor for frequent mutations leading to breast cancer and has also shed light on genetic origins in different ethnic groups within Pakistan. World-wide research efforts on different ethnicities have enhanced our understanding of genetic predisposition to breast cancer but despite these discoveries, 75% of the familial risk of breast cancer remains unexplained, highlighting the fact that the majority of breast cancer susceptibility genes remain unidentified. For this purpose Pakistani population provides a strong genetic pool to elucidate the genetic etiology of breast cancer because of cousin marriages. In this review, we describe the known breast cancer predisposition factors found in the local Pakistani population and the epidemiological research work done to emphasize the importance of exploring factors/variants contributing to breast cance, in order to prevent, cure and decrease its incidence in our country.

Histone H1 and Chromosomal Protein HMGN2 Regulate Prolactin-induced STAT5 Transcription Factor Recruitment and Function in Breast Cancer Cells.

PubMed

Schauwecker, Suzanne M; Kim, J Julie; Licht, Jonathan D; Clevenger, Charles V

2017-02-10

The hormone prolactin (PRL) contributes to breast cancer pathogenesis through various signaling pathways, one of the most notable being the JAK2/signal transducer and activator of transcription 5 (STAT5) pathway. PRL-induced activation of the transcription factor STAT5 results in the up-regulation of numerous genes implicated in breast cancer pathogenesis. However, the molecular mechanisms that enable STAT5 to access the promoters of these genes are not well understood. Here, we show that PRL signaling induces chromatin decompaction at promoter DNA, corresponding with STAT5 binding. The chromatin-modifying protein high mobility group nucleosomal binding domain 2 (HMGN2) specifically promotes STAT5 accessibility at promoter DNA by facilitating the dissociation of the linker histone H1 in response to PRL. Knockdown of H1 rescues the decrease in PRL-induced transcription following HMGN2 knockdown, and it does so by allowing increased STAT5 recruitment. Moreover, H1 and STAT5 are shown to function antagonistically in regulating PRL-induced transcription as well as breast cancer cell biology. While reduced STAT5 activation results in decreased PRL-induced transcription and cell proliferation, knockdown of H1 rescues both of these effects. Taken together, we elucidate a novel mechanism whereby the linker histone H1 prevents STAT5 binding at promoter DNA, and the PRL-induced dissociation of H1 mediated by HMGN2 is necessary to allow full STAT5 recruitment and promote the biological effects of PRL signaling. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Protein arginine methyltransferase 7 promotes breast cancer cell invasion through the induction of MMP9 expression

PubMed Central

Baldwin, R. Mitchell; Haghandish, Nasim; Daneshmand, Manijeh; Amin, Shahrier; Paris, Geneviève; Falls, Theresa J.; Bell, John C.; Islam, Shahidul; Côté, Jocelyn

2015-01-01

Recent evidence points to the protein arginine methyltransferase (PRMT) family of enzymes playing critical roles in cancer. PRMT7 has been identified in several gene expression studies to be associated with increased metastasis and decreased survival in breast cancer patients. However, this has not been extensively studied. Here we report that PRMT7 expression is significantly upregulated in both primary breast tumour tissues and in breast cancer lymph node metastases. We have demonstrated that reducing PRMT7 levels in invasive breast cancer cells using RNA interference significantly decreased cell invasion in vitro and metastasis in vivo. Conversely, overexpression of PRMT7 in non-aggressive MCF7 cells enhanced their invasiveness. Furthermore, we show that PRMT7 induces the expression of matrix metalloproteinase 9 (MMP9), a well-known mediator of breast cancer metastasis. Importantly, we significantly rescued invasion of aggressive breast cancer cells depleted of PRMT7 by the exogenous expression of MMP9. Our results demonstrate that upregulation of PRMT7 in breast cancer may have a significant role in promoting cell invasion through the regulation of MMP9. This identifies PRMT7 as a novel and potentially significant biomarker and therapeutic target for breast cancer. PMID:25605249

Protein arginine methyltransferase 7 promotes breast cancer cell invasion through the induction of MMP9 expression.

PubMed

Baldwin, R Mitchell; Haghandish, Nasim; Daneshmand, Manijeh; Amin, Shahrier; Paris, Geneviève; Falls, Theresa J; Bell, John C; Islam, Shahidul; Côté, Jocelyn

2015-02-20

Recent evidence points to the protein arginine methyltransferase (PRMT) family of enzymes playing critical roles in cancer. PRMT7 has been identified in several gene expression studies to be associated with increased metastasis and decreased survival in breast cancer patients. However, this has not been extensively studied. Here we report that PRMT7 expression is significantly upregulated in both primary breast tumour tissues and in breast cancer lymph node metastases. We have demonstrated that reducing PRMT7 levels in invasive breast cancer cells using RNA interference significantly decreased cell invasion in vitro and metastasis in vivo. Conversely, overexpression of PRMT7 in non-aggressive MCF7 cells enhanced their invasiveness. Furthermore, we show that PRMT7 induces the expression of matrix metalloproteinase 9 (MMP9), a well-known mediator of breast cancer metastasis. Importantly, we significantly rescued invasion of aggressive breast cancer cells depleted of PRMT7 by the exogenous expression of MMP9. Our results demonstrate that upregulation of PRMT7 in breast cancer may have a significant role in promoting cell invasion through the regulation of MMP9. This identifies PRMT7 as a novel and potentially significant biomarker and therapeutic target for breast cancer.

Analysis of Factors Associated With Radiation-Induced Bronchiolitis Obliterans Organizing Pneumonia Syndrome After Breast-Conserving Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Katayama, Norihisa; Sato, Shuhei; Katsui, Kuniaki

Purpose: To evaluate factors associated with radiation-induced bronchiolitis obliterans organizing pneumonia (BOOP) syndrome after breast-conserving therapy. Methods and Materials: A total of 702 women with breast cancer who received radiotherapy after breast-conserving surgery at seven institutions between July 1995 and December 2006 were analyzed. In all patients, the whole breast was irradiated with two tangential photon beams. The criteria used for the diagnosis of radiation-induced BOOP syndrome were as follows: (1) radiotherapy to the breast within 12 months, (2) general and/or respiratory symptoms lasting for {>=}2 weeks, (3) radiographs showing lung infiltration outside the radiation port, and (4) no evidencemore » of a specific cause. Results: Radiation-induced BOOP syndrome was seen in 16 patients (2.3%). Eleven patients (68.8%) were administered steroids. The duration of steroid administration ranged from 1 week to 3.7 years (median, 1.1 years). Multivariate analysis revealed that age ({>=}50 years; odds ratio [OR] 8.88; 95% confidence interval [CI] 1.16-67.76; p = 0.04) and concurrent endocrine therapy (OR 3.05; 95% CI 1.09-8.54; p = 0.03) were significantly associated with BOOP syndrome. Of the 161 patients whose age was {>=}50 years and who received concurrent endocrine therapy, 10 (6.2%) developed BOOP syndrome. Conclusions: Age ({>=}50 years) and concurrent endocrine therapy can promote the development of radiation-induced BOOP syndrome after breast-conserving therapy. Physicians should carefully follow patients who received breast-conserving therapy, especially those who are older than 50 years and received concurrent endocrine therapy during radiotherapy.« less

Socio-demographic correlates of breast-feeding in urban slums of Chandigarh.

PubMed

Kumar, Dinesh; Agarwal, Neeraj; Swami, H M

2006-11-01

Whether socio-demographic factors are associated with initiation of breast-feeding in urban slums of Chandigarh. (1) To study the prevailing breast-feeding practices adopted by mothers, (2) To study the socio-demographic factors associated with initiation of breast-feeding. Cross-sectional. Mothers of infants willing to participate in the study in the selected area. A total of 270 respondents. Social and demographic characteristics like age, socioeconomic status, educational level, birth interval, parity, gender preference, natal care practices, etc.; and variables related to various aspects of breast-feeding practices like prelacteal feed, initiation of feeding, colostrum feeding, reasons of discarding colostrum, etc. Chi-square test and odd ratios along with their respective 95% confidence intervals, multiple logistic regression analysis. Out of all 270 respondents, 159 (58.9%) initiated breast-feeding within 6 h of birth, only 43 (15.9%) discarded colostrum and 108 (40.0%) mothers gave prelacteal feed. Illiterate/just literate mothers who delivered at home were found at significantly higher risk of delay in initiation of breast-feeding on the basis of multiple logistic regression analysis. Promotion of institutional deliveries and imparting health education to mothers for protecting and promoting optimal breast-feeding practices are suggested.

[Effect of a campaign to promote breast-feeding among women in the province of Malaga who had their babies by caesarean section].

PubMed

Gámez Requena, J J; Márquez Feu, T; Gómez Gómez, F J; Sánchez García, E

2004-05-31

To determine whether an intervention to foster breast-feeding did actually increase it and how long it lasted in nursing mothers who gave birth through caesarean section. Evaluation of a community intervention. Mother-and-Child Hospital in Málaga. Sample of 152 pregnant women who delivered their baby by caesarean section, 76 in 1996 and 76 in 1998. During 1997, activities to promote breast-feeding were organised in the health district. These included workshops aimed at primary care and specialist professionals, public events to promote breast-feeding (public feeds, photography competitions, media comment, etc), accords with institutions (university, nursing college inter al) and changes in the health services (improvement of services to new mothers and neonates; co-ordination between primary and hospital care). In 1996, only 28% of women who started feeding did so with serotherapy. In 1998 this became 85% (P<.0005). Length of breast-feeding also increased significantly (P<.215). There was greater involvement of nursing, though it was not statistically significant (P<.06), moving from 40% in 1996 to 65.2% in 1998. The campaign showed its efficacy as a method of promotion of breast-feeding, on achieving an earlier start in breast-feeding, longer duration of it and greater involvement of nurses. Practical applications included changes in hospital routines, professional training, working out of strategies and specific records for the ongoing assessment of breast-feeding.

Risk Factors for Breast Cancer, Including Occupational Exposures

PubMed Central

Meo, Margrethe; Vainio, Harri

2011-01-01

The knowledge on the etiology of breast cancer has advanced substantially in recent years, and several etiological factors are now firmly established. However, very few new discoveries have been made in relation to occupational risk factors. The International Agency for Research on Cancer has evaluated over 900 different exposures or agents to-date to determine whether they are carcinogenic to humans. These evaluations are published as a series of Monographs (www.iarc.fr). For breast cancer the following substances have been classified as "carcinogenic to humans" (Group 1): alcoholic beverages, exposure to diethylstilbestrol, estrogen-progestogen contraceptives, estrogen-progestogen hormone replacement therapy and exposure to X-radiation and gamma-radiation (in special populations such as atomic bomb survivors, medical patients, and in-utero exposure). Ethylene oxide is also classified as a Group 1 carcinogen, although the evidence for carcinogenicity in epidemiologic studies, and specifically for the human breast, is limited. The classification "probably carcinogenic to humans" (Group 2A) includes estrogen hormone replacement therapy, tobacco smoking, and shift work involving circadian disruption, including work as a flight attendant. If the association between shift work and breast cancer, the most common female cancer, is confirmed, shift work could become the leading cause of occupational cancer in women. PMID:22953181

Hormonal and reproductive risk factors associated with breast cancer in Isfahan patients

PubMed Central

Tazhibi, Mehdi; Dehghani, Mohsen; Babazadeh, Shadi; Makkarian, Fariborz; Tabatabaeian, Maryam; Sadeghi, Masoumeh; Rezaei, Parisa; Faghihi, Mehri

2014-01-01

Background: Breast cancer is the most prevalent type of cancer among Iranian females; it is noteworthy that the condition of this type of cancer among Iranian women does not significantly differ from what has been reported from other countries. Considering the importance of this issue, identification of the backgrounds factors and risk factors of the breast cancer risk are highly needed. Therefore, the present study is aimed to compare the risk factors of resident patients of Isfahan province, Iran, with accredited risk factors by other countries and also identify the importance of each factor in the incidence of cancer. Materials and Methods: The present work is a case-control study, which was conducted in 2011. In order to conduct the study, 216 women who had been clinically identified with breast cancer were selected from Seiedo-Shohada Hospital, Isfahan, Iran, as the case group. Moreover, 41 healthy women who were the relatives of the selected patients (i.e., sisters and aunts) were selected as the control group. The data and information of the patients from 1999 to 2010 were collected from either assessing the database system of the center for breast cancer research or interviewing the patients through phone. To analyze the data, multiple logistic regression method was applied. Results: The range of age among selected individuals in this study was from 20-75 years old. The determinant factors for odds of breast cancer included in the applied multiple logistic regression model were the use of oral contraceptive pills (OCPs) (odds ratio [OR] =0.18, 95% confidence interval [CI] = 0.04-0.75) as the protective factor, hormone replacement therapy (OR = 10.2, 95% CI = 1.18-88.89) and menopause at old age (OR = 1.26, 95% CI = 1.11-2.12) as the risk factors. Furthermore, there was not seen any significant relationship between age, vocation, and marital status with odds of breast cancer in multiple model. Conclusion: Based on the results, use of OCPs as protective

NFκBP65 transcription factor modulates resistance to doxorubicin through ABC transporters in breast cancer.

PubMed

Velaei, Kobra; Samadi, Nasser; Soltani, Sina; Barazvan, Balal; Soleimani Rad, Jafar

2017-07-01

Shedding light on chemoresistance biology of breast cancer could contribute to enhance the clinical outcome. Intrinsic or acquired resistance to chemotherapy is a major problem in breast cancer treatment. The NFκB pathway by siRNAP65 and JSH-23 as a translocational inhibitor of NFκBP65 in the doxorubicin-resistant MCF-7 (MCF-7/Dox) and MCF-7 cells was blocked. Then, the ABC transporter expression and function were assessed by real-time qRT-PCR and flow cytometry, respectively. Induction of apoptosis was evaluated after inhibition of the NFΚB pathway as well. Our study underlined the upregulation of NFκBP65 and anti-apoptotic Bcl-2 and downregulation of pro-apoptotic Bax in the MCF-7/Dox cells compared with control MCF-7 cells. Here, we showed that interplay between nuclear factor kappa B P65 (NFkBP65) as a transcriptional regulator and ABC transporters in the MCF-7/Dox cancer cells. We found that inhibition of the elevated expression of NFκBP65 in the resistant breast cancer, whether translocational inhibition or silencing by siRNA, decreased the expression and function of MDR1 and MRP1 efflux pumps. Furthermore, the blockade of NFκBP65 promoted apoptosis via modulating Bcl-2 and BAX expression. After inhibition of the NFκBP65 signaling pathway, elevated baseline expression of survival Bcl-2 gene in the resistant breast cells significantly decreased. Suppression of the NFκB pathway has a profound dual impact on promoting the intrinsic apoptotic pathway and reducing ABC transporter function and expression, which are some of the chemoresistance features. It was speculated that the NFκB pathway directly acts on doxorubicin-induced MDR1 and MRP1 expression in MCF-7/Dox cells.

Peroxisome Proliferator Activated Receptor-α/Hypoxia Inducible Factor-1α Interplay Sustains Carbonic Anhydrase IX and Apoliprotein E Expression in Breast Cancer Stem Cells

PubMed Central

Papi, Alessio; Storci, Gianluca; Guarnieri, Tiziana; De Carolis, Sabrina; Bertoni, Sara; Avenia, Nicola; Sanguinetti, Alessandro; Sidoni, Angelo; Santini, Donatella; Ceccarelli, Claudio; Taffurelli, Mario; Orlandi, Marina; Bonafé, Massimiliano

2013-01-01

Aims Cancer stem cell biology is tightly connected to the regulation of the pro-inflammatory cytokine network. The concept of cancer stem cells “inflammatory addiction” leads to envisage the potential role of anti-inflammatory molecules as new anti-cancer targets. Here we report on the relationship between nuclear receptors activity and the modulation of the pro-inflammatory phenotype in breast cancer stem cells. Methods Breast cancer stem cells were expanded as mammospheres from normal and tumor human breast tissues and from tumorigenic (MCF7) and non tumorigenic (MCF10) human breast cell lines. Mammospheres were exposed to the supernatant of breast tumor and normal mammary gland tissue fibroblasts. Results In mammospheres exposed to the breast tumor fibroblasts supernatant, autocrine tumor necrosis factor-α signalling engenders the functional interplay between peroxisome proliferator activated receptor-α and hypoxia inducible factor-1α (PPARα/HIF1α). The two proteins promote mammospheres formation and enhance each other expression via miRNA130b/miRNA17-5p-dependent mechanism which is antagonized by PPARγ. Further, the PPARα/HIF1α interplay regulates the expression of the pro-inflammatory cytokine interleukin-6, the hypoxia survival factor carbonic anhydrase IX and the plasma lipid carrier apolipoprotein E. Conclusion Our data demonstrate the importance of exploring the role of nuclear receptors (PPARα/PPARγ) in the regulation of pro-inflammatory pathways, with the aim to thwart breast cancer stem cells functioning. PMID:23372804

What causes breast cancer? A systematic review of causal attributions among breast cancer survivors and how these compare to expert-endorsed risk factors.

PubMed

Dumalaon-Canaria, Jo Anne; Hutchinson, Amanda D; Prichard, Ivanka; Wilson, Carlene

2014-07-01

The aim of this paper was to review published research that analyzed causal attributions for breast cancer among women previously diagnosed with breast cancer. These attributions were compared with risk factors identified by published scientific evidence in order to determine the level of agreement between cancer survivors' attributions and expert opinion. A comprehensive search for articles, published between 1982 and 2012, reporting studies on causal attributions for breast cancer among patients and survivors was undertaken. Of 5,135 potentially relevant articles, 22 studies met the inclusion criteria. Two additional articles were sourced from reference lists of included studies. Results indicated a consistent belief among survivors that their own breast cancer could be attributed to family history, environmental factors, stress, fate, or chance. Lifestyle factors were less frequently identified, despite expert health information highlighting the importance of these factors in controlling and modifying cancer risk. This review demonstrated that misperceptions about the contribution of modifiable lifestyle factors to the risk of breast cancer have remained largely unchanged over the past 30 years. The findings of this review indicate that beliefs about the causes of breast cancer among affected women are not always consistent with the judgement of experts. Breast cancer survivors did not regularly identify causal factors supported by expert consensus such as age, physical inactivity, breast density, alcohol consumption, and reproductive history. Further research examining psychological predictors of attributions and the impact of cancer prevention messages on adjustment and well-being of cancer survivors is warranted.

Do socioeconomic factors influence breast cancer screening practices among Arab women in Qatar?

PubMed Central

Donnelly, Tam Truong; Al Khater, Al-Hareth; Al Kuwari, Mohamed Ghaith; Al-Bader, Salha Bujassoum; Al-Meer, Nabila; Abdulmalik, Mariam; Singh, Rajvir; Chaudhry, Sofia; Fung, Tak

2015-01-01

Objectives Breast cancer incidence rates are rising in Qatar. Although the Qatari government provides subsidised healthcare and screening programmes that reduce cost barriers for residents, breast cancer screening (BCS) practices among women remain low. This study explores the influence of socioeconomic status on BCS among Arab women in Qatar. Setting A multicentre, cross-sectional quantitative survey was conducted with 1063 Arab women (87.5% response rate) in Qatar from March 2011 to July 2011. Women who were 35 years or older and had lived in Qatar for at least 10 years were recruited from seven primary healthcare centres and women's health clinics in urban and semiurban regions of Qatar. Associations between socioeconomic factors and BCS practice were estimated using χ2 tests and multivariate logistic regression analyses. Results Findings indicate that less than one-third of the participants practised BCS appropriately, whereas less than half of the participants were familiar with recent BCS guidelines. Married women and women with higher education and income levels were significantly more likely to be aware of and to practise BCS than women who had lower education and income levels. Conclusions Findings indicate low levels of awareness and low participation rates in BCS among Arab women in Qatar. Socioeconomic factors influence these women's participation in BCS activities. The strongest predictors for BCS practice are higher education and higher income levels. Recommendations Additional research is needed to explore the impact of economic factors on healthcare seeking behaviours in the Middle Eastern countries that have a high national gross domestic product where healthcare services are free or heavily subsidised by the government; promotion of BCS and intervention strategies in these countries should focus on raising awareness about breast cancer, the cost and benefit of early screening for this disease, particularly among low-income women. PMID

Associations of Breast Density With Demographic, Reproductive, and Lifestyle Factors in a Developing Southeast Asian Population.

PubMed

Dung Yun Trieu, Phuong; Mello-Thoms, Claudia; Peat, Jennifer K; Doan Do, Thuan; Brennan, Patrick C

2017-07-01

The aim of this study was to investigate how breast density interacted with demographic, reproductive, and lifestyle features among Vietnamese women. Mammographic density and established risk factors for breast cancer were collected from 1651 women (345 cancer cases and 1306 normal cases) in Vietnam. The association of breast density categories with potential risk factors was investigated using Spearman's test for continuous variables and χ 2 tests for categorical variables. Independent factors associated with high breast density and breast cancer in specific density groupings were assessed using logistic regression. Results showed that high breast density was significantly associated with young age, low body mass index, low number of children, early age at having the last child, premenopausal status, and increased vegetable consumption. Reproductive factors were key agents associated with breast cancer for women with high breast density, which was not so evident for women with low breast density.

Twist promotes tumor metastasis in basal-like breast cancer by transcriptionally upregulating ROR1.

PubMed

Cao, Jingying; Wang, Xin; Dai, Tao; Wu, Yuanzhong; Zhang, Meifang; Cao, Renxian; Zhang, Ruhua; Wang, Gang; Jiang, Rou; Zhou, Binhua P; Shi, Jian; Kang, Tiebang

2018-01-01

Rationale: Twist is a key transcription factor for induction of epithelial-mesenchymal transition (EMT), which promotes cell migration, invasion, and cancer metastasis, confers cancer cells with stem cell-like characteristics, and provides therapeutic resistance. However, the functional roles and targeted genes of Twist in EMT and cancer progression remain elusive. Methods: The potential targeted genes of Twist were identified from the global transcriptomes of T47D/Twist cells by microarray analysis. EMT phenotype was detected by western blotting and immunofluorescence of marker proteins. The dual-luciferase reporter and chromatin immunoprecipitation assays were employed to observe the direct transcriptional induction of ROR1 by Twist. A lung metastasis model was used to study the pro-metastatic role of Twist and ROR1 by injecting MDA-MB-231 cells into tail vein of nude mice. Bio-informatics analysis was utilized to measure the metastasis-free survival of breast cancer patients. Results: Twist protein was proved to directly activate the transcription of ROR1 gene, a receptor of Wnt5a in non-canonical WNT signaling pathway. Silencing of ROR1 inhibited EMT process, cell migration, invasion, and cancer metastasis of basal-like breast cancer (BLBC) cells. Knockdown of ROR1 also ameliorated the pro-metastatic effect of Twist. Furthermore, analyses of clinical specimens indicated that high expression of both ROR1 and Twist tightly correlates with poor metastasis-free survival of breast cancer patients. Conclusion: ROR1 is a targeted gene of Twist. Twist/ROR1 signaling is critical for invasion and metastasis of BLBC cells.

Strategies for piloting a breast health promotion program in the Chinese-Australian population.

PubMed

Koo, Fung Kuen; Kwok, Cannas; White, Kate; D'Abrew, Natalie; Roydhouse, Jessica K

2012-01-01

In Australia, women from non-English-speaking backgrounds participate less frequently in breast cancer screening than English-speaking women, and Chinese immigrant women are 50% less likely to participate in breast examinations than Australian-born women. Chinese-born Australians comprise 10% of the overseas-born Australian population, and the immigrant Chinese population in Australia is rapidly increasing. We report on the strategies used in a pilot breast health promotion program, Living with Healthy Breasts, aimed at Cantonese-speaking adult immigrant women in Sydney, Australia. The program consisted of a 1-day education session and a 2-hour follow-up session. We used 5 types of strategies commonly used for cultural targeting (peripheral, evidential, sociocultural, linguistic, and constituent-involving) in a framework of traditional Chinese philosophies (Confucianism, Taoism, and Buddhism) to deliver breast health messages to Chinese-Australian immigrant women. Creating the program's content and materials required careful consideration of color (pink to indicate femininity and love), symbols (peach blossoms to imply longevity), word choice (avoidance of the word death), location and timing (held in a Chinese restaurant a few months after the Chinese New Year), communication patterns (the use of metaphors and cartoons for discussing health-related matters), and concern for modesty (emphasizing that all presenters and team members were female) to maximize cultural relevance. Using these strategies may be beneficial for designing and implementing breast cancer prevention programs in Cantonese-speaking Chinese immigrant communities.

Epidemiological risk factors associated with inflammatory breast cancer subtypes.

PubMed

Atkinson, Rachel L; El-Zein, Randa; Valero, Vicente; Lucci, Anthony; Bevers, Therese B; Fouad, Tamer; Liao, Weiqin; Ueno, Naoto T; Woodward, Wendy A; Brewster, Abenaa M

2016-03-01

In this single-institution case-control study, we identified risk factors associated with inflammatory breast cancer (IBC) subtypes based on staining of estrogen receptor (ER), progesterone receptor (PR) and expression of human epidermal growth factor 2 (HER2neu) to determine distinct etiologic pathways. We identified 224 women with IBC and 396 cancer-free women seen at the MD Anderson Cancer Center. Multinomial logistic regression was used to estimate odds ratios (ORs) and 95 % confidence intervals (CIs) for associations between breast cancer risk factors and the IBC tumor subtypes: luminal (ER+ and/or PR+/HER2neu-), HER2neu+ (any ER and PR, HER2neu+), and triple-negative (ER-/PR-/HER2neu-). In multivariable analysis, compared with women age ≥26 at first pregnancy, women age <26 had a higher risk of triple-negative IBC (OR 3.32, 95% CI 1.37-8.05). Women with a history of breast-feeding had a lower risk of triple-negative (OR 0.30; 95% CI 0.15-0.62) and luminal IBC (OR 0.35, 95% CI 0.18-0.68). A history of smoking was associated with an increased risk of luminal IBC (OR 2.37; 95% CI 1.24-4.52). Compared with normal-weight women, those who were overweight or obese (body mass index ≥25 kg/m(2)) had a higher risk of all three tumor subtypes (p < 0.01 for all subtypes). Overweight or obese status is important modifiable risk factor for IBC of any subtype. Modifiable risk factors, age at first pregnancy (≥26), breast-feeding, and smoking may be associated with specific IBC subtypes. These results highlight the importance of evaluating epidemiologic risk factors for IBC for the identification of subtype-specific prevention strategies.

Factors Predictive of Sentinel Lymph Node Involvement in Primary Breast Cancer.

PubMed

Malter, Wolfram; Hellmich, Martin; Badian, Mayhar; Kirn, Verena; Mallmann, Peter; Krämer, Stefan

2018-06-01

Sentinel lymph node biopsy (SLNB) has replaced axillary lymph node dissection (ALND) for axillary staging in patients with early-stage breast cancer. The need for therapeutic ALND is the subject of ongoing debate especially after the publication of the ACOSOG Z0011 trial. In a retrospective trial with univariate and multivariate analyses, factors predictive of sentinel lymph node involvement should be analyzed in order to define tumor characteristics of breast cancer patients, where SLNB should not be spared to receive important indicators for adjuvant treatment decisions (e.g. thoracic wall irradiation after mastectomy with or without reconstruction). Between 2006 and 2010, 1,360 patients with primary breast cancer underwent SLNB with/without ALND with evaluation of tumor localization, multicentricity and multifocality, histological subtype, tumor size, grading, lymphovascular invasion (LVI), and estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 status. These characteristics were retrospectively analyzed in univariate and multivariate logistic regression models to define significant predictive factors for sentinel lymph node involvement. The multivariate analysis demonstrated that tumor size and LVI (p<0.001) were independent predictive factors for metastatic sentinel lymph node involvement in patients with early-stage breast cancer. Because of the increased risk for metastatic involvement of axillary sentinel nodes in cases with larger breast cancer or diagnosis of LVI, patients with these breast cancer characteristics should not be spared from SLNB in a clinically node-negative situation in order to avoid false-negative results with a high potential for wrong indication of primary breast reconstruction or wrong non-indication of necessary post-mastectomy radiation therapy. The prognostic impact of avoidance of axillary staging with SLNB is analyzed in the ongoing prospective INSEMA trial. Copyright© 2018, International

Adipokines in human breast milk.

PubMed

Kratzsch, Juergen; Bae, Yoon Ju; Kiess, Wieland

2018-01-01

The review describes the molecular characteristics of so far detected breast milk adipokines and ranks their breast milk level compared to the respective levels in maternal and infant blood. Moreover, analytical knowledge for measurements of breast milk adipokines will be delineated. Next, we summarized data about two main potential influencing factors on adipokine concentration in breast milk, maternal weight and pasteurization of milk. Finally, associations between adipokines in breast milk and weight gain in infants as well as the putative mechanisms for effects of breast milk adipokines on food intake and weight gain in later life will debated. Our findings suggest that a source of adipokines in human breast milk cannot be uniformly defined. In dependence on the ratio between serum and breast milk levels the major quantity of these proteins may be derived from peripheral tissues, from the breast tissue itself or from both. Thus, leptin and in part adiponectin levels in breast milk are dependent on a plenty of influencing factors with an important relevance of maternal anthropometric characteristics There is some evidence that leptin, adiponectin and ghrelin levels in breast milk may be associated with growth gain of infants and even with increased risk for being overweight during infancy or childhood. We hypothesize that a dysregulation in adipokine homeostasis in early life could promote obesity and metabolic disturbance in later life. Copyright © 2018 Elsevier Ltd. All rights reserved.

Promoter-level expression clustering identifies time development of transcriptional regulatory cascades initiated by ErbB receptors in breast cancer cells.

PubMed

Mina, Marco; Magi, Shigeyuki; Jurman, Giuseppe; Itoh, Masayoshi; Kawaji, Hideya; Lassmann, Timo; Arner, Erik; Forrest, Alistair R R; Carninci, Piero; Hayashizaki, Yoshihide; Daub, Carsten O; Okada-Hatakeyama, Mariko; Furlanello, Cesare

2015-07-16

The analysis of CAGE (Cap Analysis of Gene Expression) time-course has been proposed by the FANTOM5 Consortium to extend the understanding of the sequence of events facilitating cell state transition at the level of promoter regulation. To identify the most prominent transcriptional regulations induced by growth factors in human breast cancer, we apply here the Complexity Invariant Dynamic Time Warping motif EnRichment (CIDER) analysis approach to the CAGE time-course datasets of MCF-7 cells stimulated by epidermal growth factor (EGF) or heregulin (HRG). We identify a multi-level cascade of regulations rooted by the Serum Response Factor (SRF) transcription factor, connecting the MAPK-mediated transduction of the HRG stimulus to the negative regulation of the MAPK pathway by the members of the DUSP family phosphatases. The finding confirms the known primary role of FOS and FOSL1, members of AP-1 family, in shaping gene expression in response to HRG induction. Moreover, we identify a new potential regulation of DUSP5 and RARA (known to antagonize the transcriptional regulation induced by the estrogen receptors) by the activity of the AP-1 complex, specific to HRG response. The results indicate that a divergence in AP-1 regulation determines cellular changes of breast cancer cells stimulated by ErbB receptors.

The Contribution of Matrix Metalloproteinase-7 Promoter Genotypes in Breast Cancer in Taiwan.

PubMed

Chou, An-Kuo; Hsiao, Chieh-Lun; Shih, Tzu-Ching; Wang, Hwei-Chung; Tsai, Chia-Wen; Chang, Wen-Shin; Liu, Liang-Chih; Way, Tzong-DER; Chung, Jing-Gung; Bau, DA-Tian

2017-09-01

The matrix metalloproteinase (MMP) family of enzymes are in charge of degradation of various components of the extracellular matrix and their functional genetic polymorphisms may be associated with cancer susceptibility. The functional polymorphisms in the promoter region of MMP7 (A-181G and C-153T) have been reported to influence the binding capacity of nuclear proteins and may contribute to genetic susceptibility to cancer. In this study, we focused on investigating the contribution of the genotypes of MMP7 (A-181G and C-153T) to breast cancer in Taiwan. These two polymorphisms were genotyped in 1,232 patients with breast cancer and 1,232 controls by polymerase chain reaction-restriction fragment length polymorphism methodology. The odds ratios (ORs) after adjusting for age, family history of cancer, smoking and alcohol drinking status for those carrying AG and GG genotypes at MMP7 promoter A-181G were 1.22 (95%CI=0.91-1.63, p=0.2235) and 2.84 (95%CI=1.64-7.48, p=0.0007) respectively, compared to those carrying the wild-type AA genotype. Supporting this finding, the adjusted OR for those carrying the G allele at MMP7 promoter A-181G was 1.57 (95%CI=1.29-1.93, p=0.0008), compared to those carrying the wild-type A allele. There was no polymorphic genotype at MMP7 C-153T found among any of the investigated individuals. Our findings suggest that the MMP7 A-181G polymorphisms may play a role in determining personal cancer susceptibility and GG genotype at MMP7 A-181G may serve as a biomarker for early detection and prediction of breast cancer in Taiwanese. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Association between lifestyle, menstrual/reproductive history, and histological factors and risk of breast cancer in women biopsied for benign breast disease.

PubMed

Arthur, Rhonda; Wang, Yihong; Ye, Kenny; Glass, Andrew G; Ginsberg, Mindy; Loudig, Olivier; Rohan, Thomas

2017-10-01

Women with benign breast disease (BBD) have an increased risk of subsequent breast cancer. However, whether conventional breast cancer risk factors influence risk of breast cancer among women with BBD is unclear. In this study, we investigated the associations of lifestyle, menstrual/reproductive, and histological factors with risk of breast cancer among women biopsied for BBD. We conducted a case-control study, nested within a cohort of 15,395 women biopsied for BBD at Kaiser Permanente Northwest between 1971 and 2006. Cases were women who developed a subsequent invasive breast cancer during follow-up; controls were individually matched to cases on age at BBD diagnosis. A total of 526 case-control pairs were included in the study. We calculated crude and multivariable OR and 95% CI for the associations between lifestyle, menstrual/reproductive, and histological factors and breast cancer risk using conditional logistic regression. Compared to premenopausal women, postmenopausal women had reduced risk of subsequent breast cancer (OR 0.60; 95% CI 0.39-0.94), whereas women who ever used hormone replacement therapy (HRT) had increased risk (OR 3.61; 95% CI 1.68-7.75), as did women whose BBD lesion showed atypical hyperplasia (OR 5.56; 95% CI 2.05-15.06). Smoking, BMI, early menarche, multiparity (≥4), history of oophorectomy, and extent of lobular involution were not associated with risk of breast cancer. This study suggests that use of HRT and having atypical hyperplasia are associated with increased risk of breast cancer among women with BBD, while postmenopausal women with BBD have a reduced risk.

Mutant p53-associated myosin-X upregulation promotes breast cancer invasion and metastasis.

PubMed

Arjonen, Antti; Kaukonen, Riina; Mattila, Elina; Rouhi, Pegah; Högnäs, Gunilla; Sihto, Harri; Miller, Bryan W; Morton, Jennifer P; Bucher, Elmar; Taimen, Pekka; Virtakoivu, Reetta; Cao, Yihai; Sansom, Owen J; Joensuu, Heikki; Ivaska, Johanna

2014-03-01

Mutations of the tumor suppressor TP53 are present in many forms of human cancer and are associated with increased tumor cell invasion and metastasis. Several mechanisms have been identified for promoting dissemination of cancer cells with TP53 mutations, including increased targeting of integrins to the plasma membrane. Here, we demonstrate a role for the filopodia-inducing motor protein Myosin-X (Myo10) in mutant p53-driven cancer invasion. Analysis of gene expression profiles from 2 breast cancer data sets revealed that MYO10 was highly expressed in aggressive cancer subtypes. Myo10 was required for breast cancer cell invasion and dissemination in multiple cancer cell lines and murine models of cancer metastasis. Evaluation of a Myo10 mutant without the integrin-binding domain revealed that the ability of Myo10 to transport β₁ integrins to the filopodia tip is required for invasion. Introduction of mutant p53 promoted Myo10 expression in cancer cells and pancreatic ductal adenocarcinoma in mice, whereas suppression of endogenous mutant p53 attenuated Myo10 levels and cell invasion. In clinical breast carcinomas, Myo10 was predominantly expressed at the invasive edges and correlated with the presence of TP53 mutations and poor prognosis. These data indicate that Myo10 upregulation in mutant p53-driven cancers is necessary for invasion and that plasma-membrane protrusions, such as filopodia, may serve as specialized metastatic engines.

Early clinical development of epidermal growth factor receptor targeted therapy in breast cancer.

PubMed

Matsuda, Naoko; Lim, Bora; Wang, Xiaoping; Ueno, Naoto T

2017-04-01

Epidermal growth factor receptor (EGFR) targeted treatment has been evaluated but has not shown a clear clinical benefit for breast cancer. This review article aims to consider the knowledge of the biological background of EGFR pathways in dissecting clinical studies of EGFR targeted treatment in breast cancer. Areas covered: This review focuses on the role of the EGFR pathway and the investigational drugs that target EGFR for breast cancer. Expert opinion: Recent studies have indicated that EGFR targeted therapy for breast cancer has some promising effects for patients with triple-negative breast cancer, basal-like breast cancer, and inflammatory breast cancer. However, predictive and prognostic biomarkers for EGFR targeted therapy have not been identified. The overexpression or amplification of EGFR itself may not be the true factor of induction of the canonical pathway as an oncogenic driver of breast cancer. Instead, downstream, non-canonical pathways related to EGFR may contribute to some aspects of the biological behavior of breast cancer; therefore, the blockade of the receptor could result in sufficient suppression of downstream pathways to inhibit the aggressive behavior of breast cancer. Mechanistic studies to investigate the dynamic interaction between the EGFR pathway and non-canonical pathways are warranted.

Factors that influence awareness of breast cancer screening among Arab women in Qatar: results from a cross sectional survey.

PubMed

Donnelly, Tam Truong; Khater, Al-Hareth Al; Al-Bader, Salha Bujassoum; Al Kuwari, Mohammed Ghaith; Malik, Mariam; Al-Meer, Nabila; Singh, Rajvir; Fung, Tak

2014-01-01

Breast cancer is the most common cancer among women in the State of Qatar. Due to low participation in breast cancer screening (BCS) activities, women in Qatar are often diagnosed with breast cancer at advanced stages of the disease. Findings indicate that low participation rates in BCS activities are significantly related to women's low level of awareness of breast cancer screening. The objectives of this study were to: (1) determine the factors that influence Qatari women's awareness of breast cancer and its screening activities: and (2) to find ways to effectively promote breast cancer screening activities among Arabic speaking women in Qatar. A multicenter, cross-sectional quantitative survey of 1,063 (87.5% response rate) female Qatari citizens and non-Qatari Arabic-speaking residents, 35 years of age or older, was conducted in Qatar from March 2011 to July 2011. Outcome measures included participant awareness levels of the most recent national recommended guidelines of BCS, participation rates in BCS activities, and factors related to awareness of BCS activities. While most participants (90.7%) were aware of breast cancer, less than half had awareness of BCS practices (28.9% were aware of breast self-examination and 41.8% of clinical breast exams, while 26.4% knew that mammography was recommended by national screening guidelines. Only 7.6% had knowledge of all three BCS activities). Regarding BCS practice, less than one-third practiced BCS appropriately (13.9% of participants performed breast self-examination (BSE) monthly, 31.3% had a clinical breast exam (CBE) once a year or once every two years, and 26.9% of women 40 years of age or older had a mammogram once every year or two years). Awareness of BCS was significantly related to BCS practice, education level, and receipt of information about breast cancer and/or BCS from a variety of sources, particularly doctors and the media. The low levels of participation rates in BCS among Arab women in this study

Background parenchymal uptake on molecular breast imaging as a breast cancer risk factor: a case-control study.

PubMed

Hruska, Carrie B; Scott, Christopher G; Conners, Amy Lynn; Whaley, Dana H; Rhodes, Deborah J; Carter, Rickey E; O'Connor, Michael K; Hunt, Katie N; Brandt, Kathleen R; Vachon, Celine M

2016-04-26

Molecular breast imaging (MBI) is a functional test used for supplemental screening of women with mammographically dense breasts. Additionally, MBI depicts variable levels of background parenchymal uptake (BPU) within nonmalignant, dense fibroglandular tissue. We investigated whether BPU is a risk factor for breast cancer. We conducted a retrospective case-control study of 3027 eligible women who had undergone MBI between February 2004 and February 2014. Sixty-two incident breast cancer cases were identified. A total of 179 controls were matched on age, menopausal status, and MBI year. Two radiologists blinded to case status independently assessed BPU as one of four categories: photopenic, minimal to mild, moderate, or marked. Conditional logistic regression analysis was performed to estimate the associations (OR) of BPU categories (moderate or marked vs. minimal to mild or photopenic) and breast cancer risk, adjusted for other risk factors. The median age was 60.2 years (range 38-86 years) for cases vs. 60.2 years (range 38-88 years) for controls (p = 0.88). Women with moderate or marked BPU had a 3.4-fold (95 % CI 1.6-7.3) and 4.8-fold (95 % CI 2.1-10.8) increased risk of breast cancer, respectively, compared with women with photopenic or minimal to mild BPU, for two radiologists. The results were similar after adjustment for BI-RADS density (OR 3.3 [95 % CI 1.6-7.2] and OR 4.6 [95 % CI 2.1-10.5]) or postmenopausal hormone use (OR 3.6 [95 % CI 1.7-7.7] and OR 5.0 [95 % CI 2.2-11.4]). The association of BPU with breast cancer remained in analyses limited to postmenopausal women only (OR 3.8 [95 % CI 1.5-9.3] and OR 4.1 [95 % CI 1.6-10.2]) and invasive breast cancer cases only (OR 3.6 [95 % CI 1.5-8.8] and OR 4.4 [95 % CI 1.7-11.1]). Variable BPU was observed among women with similar mammographic density; the distribution of BPU categories differed across density categories (p < 0.0001). This study provides the first evidence for BPU as a risk

[Risk factors associated with breast cancer women's in Durango, Mexico].

PubMed

Sifuentes-Álvarez, Antonio; Castañeda-Martínez, Lucy Yolanda; Lugo-Nevares, Mario; Reyes-Romero, Miguel Arturo

2015-11-01

Breast cancer is a public health problem worldwide and is a priority for developing countries like ours, to establish preventive and early detection measures. In Mexico since 2006 breast cancer than cervical cancer as a cause of death in women aged 30-54 years and threatens all socioeconomic groups. The known risk factors for the occurrence of this neoplasm are early menarche, nulliparity, late age parity and late menopause and family history of breast cancer. To determine the risk factors associated with breast cancer in women in the State of Durango. Epidemiological study of 50 cases and 100 con- trols aged between 35 and 69 years old. For the calculation of sample size Schlesselman tables were used. The data was collected and analyzed in SPSS V15. We used descriptive statistics and odds ratio was calculated. Age had a mean of 50.60 years and a deviation ±9,599 for cases and 50.73 (SD ± 10.08) for controls. The hereditary familial history of breast cancer OR = 5.182 (Cl 1694-15855), higher age at first pregnancy at 30 years of age OR = 3.582 (95% CI .1.121-11.439). The results of this study suggest that reproductive and hereditary familial history may influence the development of breast cancer, which is a multifactorial disease.

Breast-feeding initiation and exclusive breast-feeding in rural Vietnam.

PubMed

Duong, Dat V; Binns, Colin W; Lee, Andy H

2004-09-01

To investigate the initiation of breast-feeding and exclusive breast-feeding within the first week after delivery for women in rural Vietnam. An interviewer-administered survey was conducted on a sample of rural women who gave birth during August-October 2002. Quang Xuong District, Thanh Hoa Province of Vietnam. Four hundred and sixty-three women participated in the study, of whom 181 delivered at the district hospital (39.1%), 229 at a commune health centre (49.5%) and 53 at home attended by a traditional birth attendant (11.4%). Although the initiation and exclusive breast-feeding rates were relatively high at 98.3% and 83.6% respectively, the premature introduction of complementary food was a great concern. Logistic regression analysis showed that, together with socio-cultural determinants such as feeding preferences of the husband and maternal grandmother, feeding practices of friends, factors relating to delivery methods, delivery locations and health problems could influence the initiation rate and breast-feeding patterns. To promote breast-feeding practices of rural mothers, health education on breast-feeding should take into account local socio-cultural features in addition to improving the counselling skills of health workers.

Confirmatory factor analysis of the Chinese Breast Cancer Screening Beliefs Questionnaire.

PubMed

Kwok, Cannas; Fethney, Judith; White, Kate

2012-01-01

Chinese women have been consistently reported as having low breast cancer screening practices. The Chinese Breast Cancer Screening Beliefs Questionnaire (CBCSB) was designed to assess Chinese Australian women's beliefs, knowledge, and attitudes toward breast cancer and screening practices. The objectives of the study were to confirm the factor structure of the CBCSB with a new, larger sample of immigrant Chinese Australian women and to report its clinical validity. A convenience sample of 785 Chinese Australian women was recruited from Chinese community organizations and shopping malls. Cronbach α was used to assess internal consistency reliability, and Amos v18 was used for confirmatory factor analysis. Clinical validity was assessed through linear regression using SPSS v18. The 3-factor structure of the CBCSB was confirmed, although the model required respecification to arrive at a suitable model fit as measured by the goodness-of-fit index (0.98), adjusted goodness-of-fit index (0.97), normed fit index (0.95), and root mean square error of approximation (0.031). Internal consistency reliability coefficients were satisfactory (>.6). Women who engaged in all 3 types of screening had more proactive attitudes to health checkups and perceived less barriers to mammographic screening. The CBCSB is a valid and reliable tool for assessing Chinese women's beliefs, knowledge, and attitudes about breast cancer and breast cancer screening practices. The CBCSB can be used for providing practicing nurses with insights into the provision of culturally sensitive breast health education.

Awareness and Misconceptions of Breast Cancer Risk Factors Among Laypersons and Physicians.

PubMed

Morère, Jean-François; Viguier, Jérôme; Couraud, Sébastien; Brignoli-Guibaudet, Lysel; Lhomel, Christine; Pivot, Xavier B; Eisinger, François

2018-03-05

Primary prevention of cancer relies on awareness of and consequent identification of risk factors. We investigated knowledge of breast cancer risk factors not only among laywomen but also among female physicians. The EDIFICE 4 nationwide observational survey was conducted by phone interviews of a representative female population (737 laywomen and 105 female physicians) aged 40-75 years, using the quota method. This analysis focuses on spontaneous replies to the question "In your opinion, what are the five main risk factors that increase the risk of breast cancer?". Heredity/Family history of breast cancer was the most widely recognized risk factor in both study populations (98.1% physicians vs. 54.2% laywomen; P ≤ 0.01). Smoking (19.0 and 17.5%) and alcohol consumption (3.8 and 5.5%) were among the lifestyle risk factors that were cited by similar proportions of physicians and laywomen, respectively. Other established risk factors were however very rarely cited by either physicians or laywomen, e.g., Exposure to medical radiation (4.8 vs. 0.4%, respectively; P ≤ 0.05) or not cited at all, i.e., Benign mastopathy and Personal history of breast cancer. This survey highlights a number of misconceptions relating to behavioral risk factors for breast cancer, including the relative impact of alcohol and tobacco consumption and the importance of menopausal status. The limited awareness of the risk related to Exposure to medical radiation, Benign mastopathy, or Personal history raises concern regarding compliance with national screening recommendations.

The evaluation of knowledge and activities of primary health care professionals in promoting breast-feeding.

PubMed

Leviniene, Giedra; Petrauskiene, Ausra; Tamuleviciene, Egle; Kudzyte, Jolanta; Labanauskas, Liutauras

2009-01-01

The objective of this study was to evaluate the knowledge and activities of Kaunas primary health care center professionals in promoting breast-feeding. A total of 84 general practitioners and 52 nurses participated in the survey, which was carried out in Kaunas primary health care centers in 2006. Data were gathered from the anonymous questionnaire. Less than half of general practitioners (45.1%) and 65% of nurses were convinced that baby must be exclusively breast-fed until the age of 6 months, but only 21.6% of general practitioners and 27.5% of nurses knew that breast-feeding with complementary feeding should be continued until the age of 2 years and longer. Still 15.7% of general practitioners and 25% of nurses recommended pacifiers; 7.8% of general practitioners advised to breast-feed according to hours. Half of the health professionals recommended additional drinks between meals; one-third of them--to give complementary food for the babies before the age of 6 months. One-third (29.6%) of the health professionals surveyed recommended mothers to feed their babies more frequently in case the amount of breast milk decreased. The survey showed that knowledge of medical personnel in primary health care centers about the advantages of breast-feeding, prophylaxis of hypogalactia, and duration of breast-feeding was still insufficient.

Fat, caloric intake, and obesity: lifestyle risk factors for breast cancer.

PubMed

Greenwald, P; Sherwood, K; McDonald, S S

1997-07-01

Dietary fat is a likely important determinant of postmenopausal breast cancer as part of an intricate and inseparable interaction of lifestyle cancer risk factors that include dietary fat, type of fat, energy intake and expenditure, and obesity. These factors possibly build upon individual susceptibilities derived from a complex array of polygenetic risk determinants. Epidemiologic studies have not provided conclusive evidence for a dietary fat-breast cancer association, partly because studies that focus on a single nutrient cannot always evaluate readily the interactive effects of other lifestyle factors. Further, persons generally underestimate their usual dietary intake, measured by either food frequency questionnaires (FFQs) or diet records. A dietary measurement model that accounts for this underreporting demonstrated that FFQs and diet records may not be able to detect a dietary fat-breast cancer association because of measurement error biases. Although meta-analysis of epidemiologic data across individual studies suggests only a week association between breast cancer and dietary fat, this result is compatible with the dietary measurement model and does not rule out a contributing role for dietary fat, either alone or with other causative factors. Research is needed that focuses on a comprehensive approach to dietary lifestyle choices and breast cancer risk and that emphasizes a fat-caloric intake-obesity linkage. The best hope for a definitive answer may rest with randomized, controlled clinical trials. Two such trials, the Women's Health Initiative and the Women's Intervention Nutrition Study, are under way.

Associations Between Religion-Related Factors and Breast Cancer Screening Among American Muslims

PubMed Central

Padela, Aasim I.; Murrar, Sohad; Adviento, Brigid; Liao, Chuanhong; Hosseinian, Zahra; Peek, Monica; Curlin, Farr

2015-01-01

American Muslims have low rates of mammography utilization, and research suggests that religious values influence their health-seeking behaviors. We assessed associations between religion-related factors and breast cancer screening in this population. A diverse group of Muslim women were recruited from mosques and Muslim organization sites in Greater Chicago to self-administer a survey incorporating measures of fatalism, religiosity, discrimination, and Islamic modesty. 254 surveys were collected of which 240 met age inclusion criteria (40 years of age or older). Of the 240, 72 respondents were Arab, 71 South Asian, 59 African American, and 38 identified with another ethnicity. 77 % of respondents had at least one mammogram in their lifetime, yet 37 % had not obtained mammography within the past 2 years. In multivariate models, positive religious coping, and perceived religious discrimination in healthcare were negatively associated with having a mammogram in the past 2 years, while having a PCP was positively associated. Ever having a mammogram was positively associated with increasing age and years of US residency, and knowing someone with breast cancer. Promoting biennial mammography among American Muslims may require addressing ideas about religious coping and combating perceived religious discrimination through tailored interventions. PMID:24700026

Associations between religion-related factors and breast cancer screening among American Muslims.

PubMed

Padela, Aasim I; Murrar, Sohad; Adviento, Brigid; Liao, Chuanhong; Hosseinian, Zahra; Peek, Monica; Curlin, Farr

2015-06-01

American Muslims have low rates of mammography utilization, and research suggests that religious values influence their health-seeking behaviors. We assessed associations between religion-related factors and breast cancer screening in this population. A diverse group of Muslim women were recruited from mosques and Muslim organization sites in Greater Chicago to self-administer a survey incorporating measures of fatalism, religiosity, discrimination, and Islamic modesty. 254 surveys were collected of which 240 met age inclusion criteria (40 years of age or older). Of the 240, 72 respondents were Arab, 71 South Asian, 59 African American, and 38 identified with another ethnicity. 77% of respondents had at least one mammogram in their lifetime, yet 37% had not obtained mammography within the past 2 years. In multivariate models, positive religious coping, and perceived religious discrimination in healthcare were negatively associated with having a mammogram in the past 2 years, while having a PCP was positively associated. Ever having a mammogram was positively associated with increasing age and years of US residency, and knowing someone with breast cancer. Promoting biennial mammography among American Muslims may require addressing ideas about religious coping and combating perceived religious discrimination through tailored interventions.

Occupational risk factors for female breast cancer: a review.

PubMed Central

Goldberg, M S; Labrèche, F

1996-01-01

OBJECTIVES: Although progress has been made in identifying personal risk factors and in improving treatment for female breast cancer, incidence rates continue to increase. With women now occupying a sizable fraction of the workforce, it is worth inquiring whether there are occupational risk factors for breast cancer. This is a review of occupational studies on female breast cancer. METHODS: Suitable reports and published articles with associations of female breast cancer and occupation were identified from technical reports, by searching the MEDLINE bibliographic data base, and by reviewing each paper on cancer that was published in 20 major journals during the period from about 1971-94. RESULTS: A total of 115 studies were identified; 19 studies relied exclusively on data collected for administrative purposes, and there were four incident case-control studies and 92 cohort studies. Although data for individual industries, occupations, and exposures were sparse, there was limited evidence of an association with employment in the pharmaceutical industry and among cosmetologists and beauticians. Associations were also found for chemists and occupations with possible exposure to extremely low frequency electromagnetic fields, but potential methodological weaknesses preclude drawing any definite conclusions. There was little support for increased risks among textiles workers, dry cleaning workers, and nuclear industry workers. CONCLUSIONS: Few high quality occupational studies directed specifically toward women have been carried out to allow the unambiguous identification of occupational risk factors for breast cancer. It is suggested that investigations that account for non-occupational risk factors and that assess exposure in a more detailed way be carried out. One strategy already suggested is to conduct population based, case-control studies in which subjects are interviewed about their occupational histories and exposure to chemical and physical agents which are

Epigenetics and Breast Cancers

PubMed Central

Vo, An T.; Millis, Richard M.

2012-01-01

Several of the active compounds in foods, poisons, drugs, and industrial chemicals may, by epigenetic mechanisms, increase or decrease the risk of breast cancers. Enzymes that are involved in DNA methylation and histone modifications have been shown to be altered in several types of breast and other cancers resulting in abnormal patterns of methylation and/or acetylation. Hypermethylation at the CpG islands found in estrogen response element (ERE) promoters occurs in conjunction with ligand-bonded alpha subunit estrogen receptor (Erα) dimers wherein the ligand ERα dimer complex acts as a transcription factor and binds to the ERE promoter. Ligands could be 17-β-estradiol (E2), phytoestrogens, heterocyclic amines, and many other identified food additives and heavy metals. The dimer recruits DNA methyltransferases which catalyze the transfer of methyl groups from S-adenosyl-L-methionine (SAM) to 5′-cytosine on CpG islands. Other enzymes are recruited to the region by ligand-ERα dimers which activate DNA demethylases to act simultaneously to increase gene expression of protooncogenes and growth-promoting genes. Ligand-ERα dimers also recruit histone acetyltransferase to the ERE promoter region. Histone demethylases such as JMJD2B and histone methyltransferases are enzymes which demethylate lysine residues on histones H3 and/or H4. This makes the chromatin accessible for transcription factors and enzymes. PMID:22567014

Analysis of the AHR gene proximal promoter GGGGC-repeat polymorphism in lung, breast, and colon cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Spink, Barbara C.; Bloom, Michael S.; Wu, Susan

The aryl hydrocarbon receptor (AhR) regulates expression of numerous genes, including those of the CYP1 gene family. With the goal of determining factors that control AHR gene expression, our studies are focused on the role of the short tandem repeat polymorphism, (GGGGC){sub n}, located in the proximal promoter of the human AHR gene. When luciferase constructs containing varying GGGGC repeats were transfected into cancer cell lines derived from the lung, colon, and breast, the number of GGGGC repeats affected AHR promoter activity. The number of GGGGC repeats was determined in DNA from 327 humans and from 38 samples representing 5more » species of non-human primates. In chimpanzees and 3 species of macaques, only (GGGGC){sub 2} alleles were observed; however, in western gorilla, (GGGGC){sub n} alleles with n = 2, 4, 5, 6, 7, and 8 were identified. In all human populations examined, the frequency of (GGGGC){sub n} was n = 4 > 5 ≫ 2, 6. When frequencies of the (GGGGC){sub n} alleles in DNA from patients with lung, colon, or breast cancer were evaluated, the occurrence of (GGGGC){sub 2} was found to be 8-fold more frequent among lung cancer patients in comparison with its incidence in the general population, as represented by New York State neonates. Analysis of matched tumor and non-tumor DNA samples from the same individuals provided no evidence of microsatellite instability. These studies indicate that the (GGGGC){sub n} short tandem repeats are inherited, and that the (GGGGC){sub 2} allele in the AHR proximal promoter region should be further investigated with regard to its potential association with lung cancer susceptibility. - Highlights: • The AHR proximal promoter contains a polymorphism, (GGGGC){sub n}, where n = 4 > 5 ≫ 2, 6 • Matched tumor and non-tumor DNA did not show (GGGGC){sub n} microsatellite instability • AHR promoter activity of a construct with (GGGGC){sub 2} was lower than that of (GGGGC){sub 4} • The frequency of (GGGGC){sub 2

Antiperspirant use as a risk factor for breast cancer in Iraq.

PubMed

Fakri, S; Al-Azzawi, A; Al-Tawil, N

2006-01-01

Some internet communications have addressed the link between antiperspirant use and breast cancer. We studied the possible association between the use of antiperspirants and some other factors with the development of breast cancer in Al-Kadhmia teaching hospital. Thus, 54 cases of breast cancer and 50 controls were interviewed. We found 82.0% of the controls used antiperspirants compared with 51.8% of cases (P< 0.05). The use of antiperspirants had no association with the risk of breast cancer, while family history and oral contraceptives use were found to be associated.

Long non-coding RNA GHET1 promotes human breast cancer cell proliferation, invasion and migration via affecting epithelial mesenchymal transition.

PubMed

Song, Rui; Zhang, Jia; Huang, Junhua; Hai, Tao

2018-05-11

Breast cancer is a common malignancy in women and long non-coding RNAs (lncRNAs) have been shown to play key roles in the development and progression of breast cancer. In the present study, we examined the biological role of lncRNA gastric carcinoma highly expressed transcript 1 (GHET1) in breast cancer. The expression of GHET1 was determined by qRT-PCR assay; CCK-8, colony formation, Transwell invasion and migration assays detected breast cancer cell proliferation, invasion and migration; cell apoptosis and cell cycle were determined by flow cytometry; protein levels were determined by western blot assay. GHET1 was up-regulated in breast cancer tissues and cell lines, and the up-regulation of GHET1 was positively correlated with larger tumor size, advanced clinical stage, lymph node metastasis and shorter overall survival. Knockdown of GHET1 suppressed cell proliferation, invasion and migration, and induced apoptosis and G0/G1 cell cycle arrest in MCF-cells. Knockdown of GHET1 also suppressed the protein levels of N-cadherin, vimentin, and decreased the protein level of E-cadherin in MCF-7 cells. On the other hand, overexpression of GHET1 promoted cell proliferation, invasion and migration, and inhibited cell apoptosis and increased cell population at S phase in BT-20 cells. Overexpression of GHET1 also promoted epithelial mesenchymal transition (EMT) in BT-20 cells. Furthermore, knockdown of GHET1 also suppressed in vivo tumor growth of MCF-7 cells, and also decreased the protein levels of N-cadherin and vimentin, and increased the protein levels of E-cadherin in the tumor tissues from the nude mice. Our results demonstrated that GHET1 was up-regulated in breast cancer tissues and cell lines, and promoted breast cancer cell proliferation, invasion and migration by affecting EMT. Our study for the first time revealed the biological functions of GHET1 in breast cancer.

The role of Tamang mothers-in-law in promoting breast feeding in Makwanpur District, Nepal.

PubMed

Masvie, Hilde

2006-03-01

to systematically analyse the Nepalise grandmother's own perspective of breast feeding. a qualitative approach was used. Three focus-group discussions and eight semi-structured interviews formed the primary database. All interviews and discussions were tape recorded, and translated transcripts and field notes were analysed. Makwanpur District, rural Nepal. 31 Tamang mothers-in-law living in a household with their son's family, and taking part in child care. the data suggest that the mothers-in-law see themselves as key providers of, and decision-makers in, perinatal care practices. Traditional patterns of promotive and preventive care were identified. contrary to the widespread reports that early breast feeding is delayed in this setting, these grandmothers held colostrum in high regard, used no prelacteals and supported early initiation of breast feeding.

Intrinsic motivation factors based on the self-determinant theory for regular breast cancer screening.

PubMed

Jung, Su Mi; Jo, Heui-Sug

2014-01-01

The purpose of this study was to identify factors of intrinsic motivation that affect regular breast cancer screening and contribute to development of a program for strategies to improve effective breast cancer screening. Subjects were residing in South Korea Gangwon-Province and were female over 40 and under 69 years of age. For the investigation, the Intrinsic Motivation Inventory (IMI) was modified to the situation of cancer screening and was used to survey 905 inhabitants. Multinominal logistic regression analyses were conducted for regular breast cancer screening (RS), one-time breast cancer screening (OS) and non-breast cancer screening (NS). For statistical analysis, IBM SPSS 20.0 was utilized. The determinant factors between RS and NS were "perceived effort and choice" and "stress and strain" - internal motivations related to regular breast cancer screening. Also, determinant factors between RS and OS are "age" and "perceived effort and choice" for internal motivation related to cancer screening. To increase regular screening, strategies that address individual perceived effort and choice are recommended.

Expression of connective tissue growth factor (CTGF/CCN2) in breast cancer cells is associated with increased migration and angiogenesis.

PubMed

Chien, Wenwen; O'Kelly, James; Lu, Daning; Leiter, Amanda; Sohn, Julia; Yin, Dong; Karlan, Beth; Vadgama, Jay; Lyons, Karen M; Koeffler, H Phillip

2011-06-01

Connective tissue growth factor (CTGF/CCN2) belongs to the CCN family of matricellular proteins, comprising Cyr61, CTGF, NovH and WISP1-3. The CCN proteins contain an N-terminal signal peptide followed by four conserved domains sharing sequence similarities with the insulin-like growth factor binding proteins, von Willebrand factor type C repeat, thrombospondin type 1 repeat, and a C-terminal growth factor cysteine knot domain. To investigate the role of CCN2 in breast cancer, we transfected MCF-7 cells with full-length CCN2, and with four mutant constructs in which one of the domains had been deleted. MCF-7 cells stably expressing full-length CCN2 demonstrated reduced cell proliferation, increased migration in Boyden chamber assays and promoted angiogenesis in chorioallantoic membrane assays compared to control cells. Deletion of the C-terminal cysteine knot domain, but not of any other domain-deleted mutants, abolished activities mediated by full-length CCN2. We have dissected the role of CCN2 in breast tumorigenesis on a structural basis.

Early clinical development of epidermal growth factor receptor targeted therapy in breast cancer

PubMed Central

Matsuda, Naoko; Lim, Bora; Wang, Xiaoping; Ueno, Naoto T.

2018-01-01

Introduction Epidermal growth factor receptor (EGFR) targeted treatment has been evaluated but has not shown a clear clinical benefit for breast cancer. This review article aims to consider the knowledge of the biological background of EGFR pathways in dissecting clinical studies of EGFR targeted treatment in breast cancer. Areas covered This review focuses on the role of the EGFR pathway and the investigational drugs that target EGFR for breast cancer. Expert opinion Recent studies have indicated that EGFR targeted therapy for breast cancer has some promising effects for patients with triple-negative breast cancer, basal-like breast cancer, and inflammatory breast cancer. However, predictive and prognostic biomarkers for EGFR targeted therapy have not been identified. The overexpression or amplification of EGFR itself may not be the true factor of induction of the canonical pathway as an oncogenic driver of breast cancer. Instead, downstream, non-canonical pathways related to EGFR may contribute to some aspects of the biological behavior of breast cancer; therefore, the blockade of the receptor could result in sufficient suppression of downstream pathways to inhibit the aggressive behavior of breast cancer. Mechanistic studies to investigate the dynamic interaction between the EGFR pathway and non-canonical pathways are warranted. PMID:28271910

Protein disulfide isomerases in the endoplasmic reticulum promote anchorage-independent growth of breast cancer cells.

PubMed

Wise, Randi; Duhachek-Muggy, Sara; Qi, Yue; Zolkiewski, Michal; Zolkiewska, Anna

2016-06-01

Metastatic breast cancer cells are exposed to stress of detachment from the extracellular matrix (ECM). Cultured breast cancer cells that survive this stress and are capable of anchorage-independent proliferation form mammospheres. The purpose of this study was to explore a link between mammosphere growth, ECM gene expression, and the protein quality control system in the endoplasmic reticulum (ER). We compared the mRNA and protein levels of ER folding factors in SUM159PT and MCF10DCIS.com breast cancer cells grown as mammospheres versus adherent conditions. Publicly available gene expression data for mammospheres formed by primary breast cancer cells and for circulating tumor cells (CTCs) were analyzed to assess the status of ECM/ER folding factor genes in clinically relevant samples. Knock-down of selected protein disulfide isomerase (PDI) family members was performed to examine their roles in SUM159PT mammosphere growth. We found that cells grown as mammospheres had elevated expression of ECM genes and ER folding quality control genes. CTC gene expression data for an index patient indicated that upregulation of ECM and ER folding factor genes occurred at the time of acquired therapy resistance and disease progression. Knock-down of PDI, ERp44, or ERp57, three members of the PDI family with elevated protein levels in mammospheres, in SUM159PT cells partially inhibited the mammosphere growth. Thus, breast cancer cell survival and growth under detachment conditions require enhanced assistance of the ER protein folding machinery. Targeting ER folding factors, in particular members of the PDI family, may improve the therapeutic outcomes in metastatic breast cancer.

Preclinical evaluation of transcriptional targeting strategies for carcinoma of the breast in a tissue slice model system

PubMed Central

Stoff-Khalili, Mariam A; Stoff, Alexander; Rivera, Angel A; Banerjee, Nilam S; Everts, Maaike; Young, Scott; Siegal, Gene P; Richter, Dirk F; Wang, Minghui; Dall, Peter; Mathis, J Michael; Zhu, Zeng B; Curiel, David T

2005-01-01

Introduction In view of the limited success of available treatment modalities for metastatic breast cancer, alternative and complementary strategies need to be developed. Adenoviral vector mediated strategies for breast cancer gene therapy and virotherapy are a promising novel therapeutic platform for the treatment of breast cancer. However, the promiscuous tropism of adenoviruses (Ads) is a major concern. Employing tissue specific promoters (TSPs) to restrict transgene expression or viral replication is an effective way to increase specificity towards tumor tissues and to reduce adverse effects in non-target tissues such as the liver. In this regard, candidate breast cancer TSPs include promoters of the genes for the epithelial glycoprotein 2 (EGP-2), cyclooxygenase-2 (Cox-2), α-chemokine SDF-1 receptor (stromal-cell-derived factor, CXCR4), secretory leukoprotease inhibitor (SLPI) and survivin. Methods We employed E1-deleted Ads that express the reporter gene luciferase under the control of the promoters of interest. We evaluated this class of vectors in various established breast cancer cell lines, primary breast cancer cells and finally in the most stringent preclinical available substrate system, constituted by precision cut tissue slices of human breast cancer and liver. Results Overall, the CXCR4 promoter exhibited the highest luciferase activity in breast cancer cell lines, primary breast cancer cells and breast cancer tissue slices. Importantly, the CXCR4 promoter displayed a very low activity in human primary fibroblasts and human liver tissue slices. Interestingly, gene expression profiles correlated with the promoter activities both in breast cancer cell lines and primary breast cancer cells. Conclusion These data suggest that the CXCR4 promoter has an ideal 'breast cancer-on/liver-off' profile, and could, therefore, be a powerful tool in Ad vector based gene therapy or virotherapy of the carcinoma of the breast. PMID:16457694

SIRT1 promotes proliferation, migration, and invasion of breast cancer cell line MCF-7 by upregulating DNA polymerase delta1 (POLD1).

PubMed

Xu, Yifang; Qin, Qinghong; Chen, Rushi; Wei, Changyuan; Mo, Qinguo

2018-07-20

Sirtuin 1 (SIRT1), class III histone deacetylase, plays an important character in cell proliferation, cell cycle, apoptosis, energy metabolism and DNA repair. In recent years, researchers have attached increasing attention on the role of SIRT1 in tumorigenesis, development and drug resistance. The effect of SIRT1 on breast cancer is still controversial and its exact role remains to be elucidated. In the present study, we investigated the significant role of SIRT1 in breast cancer by exploring the effect of SIRT1 on DNA polymerase delta1 (POLD1), the gene coding for DNA polymerase δ catalytic subunit p125. Immunohistochemistry showed that the protein expression level of SIRT1 was higher in breast cancer tissues relative to adjacent normal tissues. Knockdown of SIRT1 by shRNA decreased the proliferation, migration, and invasion of human breast cancer cell line MCF-7, while the overexpression of SIRT1 promoted the proliferation, migration, and invasion of MCF-7 cells. Clinically, the immunohistochemistry results revealed that the expression of SIRT1 was positively correlated with p125. Further analysis demonstrated that silencing of SIRT1 increased the expression of p53, while the expression level of POLD1/p125 decreased, and the result by overexpressing SIRT1 was opposite. Collectively, these data suggest that SIRT1 is an oncogenic factor in breast cancer cells and can be involved in the progression of breast cancer by inhibiting p53 and activating POLD1. Our finding provides new insights into the mechanisms of breast cancer. Copyright © 2018 Elsevier Inc. All rights reserved.

Oncogenic HER2Δ16 suppresses miR-15a/16 and deregulates BCL-2 to promote endocrine resistance of breast tumors

PubMed Central

Cittelly, Diana M.; Das, Partha M.; Salvo, Virgilio A.; Fonseca, Juan P.; Burow, Matthew E.; Jones, Frank E.

2010-01-01

Tamoxifen is the most commonly prescribed therapy for patients with estrogen receptor (ER)α-positive breast tumors. Tumor resistance to tamoxifen remains a serious clinical problem especially in patients with tumors that also overexpress human epidermal growth factor receptor 2 (HER2). Current preclinical models of HER2 overexpression fail to recapitulate the clinical spectrum of endocrine resistance associated with HER2/ER-positive tumors. Here, we show that ectopic expression of a clinically important oncogenic isoform of HER2, HER2Δ16, which is expressed in >30% of ER-positive breast tumors, promotes tamoxifen resistance and estrogen independence of MCF-7 xenografts. MCF-7/HER2Δ16 cells evade tamoxifen through upregulation of BCL-2, whereas mediated suppression of BCL-2 expression or treatment of MCF-7/HER2Δ16 cells with the BCL-2 family pharmacological inhibitor ABT-737 restores tamoxifen sensitivity. Tamoxifen-resistant MCF-7/HER2Δ16 cells upregulate BCL-2 protein levels in response to suppressed ERα signaling mediated by estrogen withdrawal, tamoxifen treatment or fulvestrant treatment. In addition, HER2Δ16 expression results in suppression of BCL-2-targeting microRNAs miR-15a and miR-16. Reintroduction of miR-15a/16 reduced tamoxifen-induced BCL-2 expression and sensitized MCF-7/HER2Δ16 to tamoxifen. Conversely, inhibition of miR-15a/16 in tamoxifen-sensitive cells activated BCL-2 expression and promoted tamoxifen resistance. Our results suggest that HER2Δ16 expression promotes endocrine-resistant HER2/ERα-positive breast tumors and in contrast to wild-type HER2, preclinical models of HER2Δ16 overexpression recapitulate multiple phenotypes of endocrine-resistant human breast tumors. The mechanism of HER2Δ16 therapeutic evasion, involving tamoxifen-induced upregulation of BCL-2 and suppression of miR-15a/16, provides a template for unique therapeutic interventions combining tamoxifen with modulation of microRNAs and/or ABT-737-mediated BCL-2

Factors Related to Incomplete Treatment of Breast Cancer in Kumasi, Ghana

PubMed Central

Obrist, Mark; Osei-Bonsu, Ernest; Ahwah, Baffour; Watanabe-Galloway, Shinobu; Merajver, Sofia D.; Schmid, Kendra; Soliman, Amr S.

2014-01-01

Purpose The burden of cancer in Africa is an enlarging public health challenge. Breast cancer in Ghana is the second most common cancer among Ghanaian women and the proportion of diagnosed patients who complete prescribed treatment is estimated to be very limited, thereby potentially adding to lower survival and poor quality of life after diagnosis. The objective of this study was to identify the patient and system factors related to incomplete treatment of breast cancer among patients. Methods This study was conducted at the Komfo Anokye Teaching Hospital in Kumasi, Ghana. We interviewed 117 breast cancer patients and next of kin of breast cancer patients diagnosed from 2008 to 2010. Results Islamic religion, seeking treatment with traditional healers, and lack of awareness about national health insurance coverage of breast cancer treatment were predictors of incomplete treatment. Conclusions The results of this study support that Ghanaian women with diagnosed breast cancer have multiple addressable and modifiable patient factors that may deter them from completing the prescribed treatment. The results highlight the need for developing and testing specific interventions about the importance of completing treatment with a special focus on addressing religious, cultural, and system navigation barriers in developing countries. PMID:25282667

Platelet Activating Factor: A Growth Factor for Breast Cancer

DTIC Science & Technology

2006-09-01

synthase (ADS) increases ether lipid content, growth and PAF synthesis in MCF-7 cells. 4. Eicosapentaenoic acid (EPA) inhibits the synthesis of PAF...Schmitt, J. D., Bullock, B. C. Wykle, R. L. Reacylation of platelet activating factor with eicosapentaenoic acid in fish-oil-enriched monkey...breast cancer. Recent studies have shown that the ratio of two families of essential fatty acids is important in regulating many cellular processes

TRIM44 Is a Poor Prognostic Factor for Breast Cancer Patients as a Modulator of NF-κB Signaling.

PubMed

Kawabata, Hidetaka; Azuma, Kotaro; Ikeda, Kazuhiro; Sugitani, Ikuko; Kinowaki, Keiichi; Fujii, Takeshi; Osaki, Akihiko; Saeki, Toshiaki; Horie-Inoue, Kuniko; Inoue, Satoshi

2017-09-08

Many of the tripartite motif (TRIM) proteins function as E3 ubiquitin ligases and are assumed to be involved in various events, including oncogenesis. In regard to tripartite motif-containing 44 (TRIM44), which is an atypical TRIM family protein lacking the RING finger domain, its pathophysiological significance in breast cancer remains unknown. We performed an immunohistochemical study of TRIM44 protein in clinical breast cancer tissues from 129 patients. The pathophysiological role of TRIM44 in breast cancer was assessed by modulating TRIM44 expression in MCF-7 and MDA-MB-231 breast cancer cells. TRIM44 strong immunoreactivity was significantly associated with nuclear grade ( p = 0.033), distant disease-free survival ( p = 0.031) and overall survival ( p = 0.027). Multivariate analysis revealed that the TRIM44 status was an independent prognostic factor for distant disease-free survival ( p = 0.005) and overall survival ( p = 0.002) of patients. siRNA-mediated TRIM44 knockdown significantly decreased the proliferation of MCF-7 and MDA-MB-231 cells and inhibited the migration of MDA-MB-231 cells. Microarray analysis and qRT-PCR showed that TRIM44 knockdown upregulated CDK19 and downregulated MMP1 in MDA-MB-231 cells. Notably, TRIM44 knockdown impaired nuclear factor-kappa B (NF-κB)-mediated transcriptional activity stimulated by tumor necrosis factor α (TNFα). Moreover, TRIM44 knockdown substantially attenuated the TNFα-dependent phosphorylation of the p65 subunit of NF-κB and IκBα in both MCF-7 and MDA-MB-231 cells. TRIM44 would play a role in the progression of breast cancer by promoting cell proliferation and migration, as well as by enhancing NF-κB signaling.

Promotion of breast feeding in the community: impact of health education programme in rural communities in Nigeria.

PubMed

Davies-Adetugbo, A A

1996-03-01

Breast feeding has been recognized as a child survival strategy, while breast feeding programmes have been increasingly implemented in many communities. This study assesses the effectiveness of a breast feeding education programme launched through the primary health care programme in the rural communities of Nigeria. Late trimester pregnant women were enrolled into the study and given a questionnaire on knowledge, attitudes, and practices (KAP) about breast feeding. Women in the study group (n = 126) received breast feeding counselling before and after delivery, while those in control group (n = 130) did not receive any counselling. Both groups were monitored after delivery and followed with the KAP questionnaire. The results of the study showed marked improvements in the intervention group for colostrum feeding (p = 0.0000). Moreover, 31.6% of the mothers in the intervention group practised timely initiation of breast feeding compared to 5.6% of the controls, and the prevalence of exclusive breast feeding at 4 months was 39.8% in the intervention group compared to 13.9% for the controls. Multivariate analysis showed that the intervention was a powerful and the only significant predictor of the increase in breast feeding behaviours (p = 0.0000), and that an early initiation of breast feeding is a strong predictor of exclusive breast feeding at 4 months of age. It is concluded that breast feeding promotion in rural communities is feasible and can lead to behavioural changes.

Clinicopathological factors associated with survival in patients with breast cancer brain metastasis.

PubMed

Li, Rong; Zhang, Kui; Siegal, Gene P; Wei, Shi

2017-06-01

Brain metastasis from breast cancer generally represents a catastrophic event yet demonstrates substantial biological heterogeneity. There have been limited studies solely focusing on the prognosis of patients with such metastasis. In this study, we carried out a comprehensive analysis in 108 consecutive patients with breast cancer brain metastases between 1997 and 2012 to further define clinicopathological factors associated with early onset of brain metastasis and survival outcomes after development of them. We found that lobular carcinoma, higher clinical stages at diagnosis, and lack of coexisting bone metastasis were significantly associated with a worse brain relapse-free survival when compared with brain-only metastasis. High histologic grade, triple-negative breast cancer, and absence of visceral involvement were unfavorable prognostic factors after brain metastasis. Furthermore, high histologic grade, advanced tumor stages, and lack of coexisting bone involvement indicated a worse overall survival. Thus, the previously established prognostic factors in early stage or advanced breast cancers may not entirely apply to patients with brain metastases. Furthermore, the prognostic significance of the clinicopathological factors differed before and after a patient develops brain metastasis. This knowledge might help in establishing an algorithm to further stratify patients with breast cancer into prognostically significant categories for optimal prevention, screening, and treatment of their brain metastasis. Copyright © 2017 Elsevier Inc. All rights reserved.

Radical and Ethnic Differences in Breast Cancer Risk Factors

DTIC Science & Technology

2001-07-01

Higher incidence or mortality from breast cancer has been reported in US migrant populations such as Asians [Buell 1973, Haenszel 1968, Locke 1980 , King... 1980 , Stanford 1995] and Hispanics [Menck 1975, Shimizu 1991] compared to the respective populations residing in Asian or Latin American countries. An...cancer risk. Br J Cancer 1993;68:627-36. Howe GR, Hirohta T, Hislop TG, et al. Dietary factors and risk of breast cancer: combined analysis of 12 case

The Relationship Between Breast Cancer and Risk Factors: A Single-Center Study.

PubMed

Ozsoy, Arzu; Barca, Nurdan; Dolek, Betul Akdal; Aktaş, Hafize; Elverici, Eda; Araz, Levent; Ozkaraoğlu, Ozlen

2017-07-01

To determine the relationship between breast cancer and known risk factors in patients who had mammography (MG) for breast cancer screening or ultrasonography and/or MG for diagnostic purposes. In the period of January-December, 2011, a questionnaire composed of 17 questions was applied to 2862 female patients and MG and/or US examination was performed afterwards. Chi-square and Kruskal-Wallis tests were used for statistical analysis. The mean age was 51.05±8.98, age at menarche was 13.0±1.6 and age at menopause was 47±5.2. The first pregnancy was at 20±4.6. Out of 2862 cases, 242 had breast cancer diagnosis and 32 were newly diagnosed. There was no correlation between menarche age, age at menopause or first pregnancy and breast cancer. There was no relationship between breast cancer risk and hormone replacement therapy or oral contraceptive use. In patients with the diagnosis of breast cancer (242 cases), 61 had (25%) a positive family history. There was a significant correlation between the presence of a positive family history and having breast cancer (p=0.003). The presence of breast cancer in the family has the strongest relationship among all risk factors. It is important to have regular followup of these patients and to raise the awareness of patients.

Clinical Presentation and Frequency of Risk Factors in Patients with Breast Carcinoma in Pakistan.

PubMed

Memon, Zahid Ali; Qurrat-ul-Ain; Khan, Ruba; Raza, Natasha; Noor, Tooba

2015-01-01

Breast cancer is known to be one of the most prevalent cancers among women in both developing and developed countries .The incidence of breast cancer in Pakistan has increased dramatically within the last few years and is the second country after Israel in Asia to have highest proportional cases of breast cancer. However, there are limited data for breast cancer available in the literature from Pakistan. The study was conducted to bring to light the common clinical presentation of breast cancer and to evaluate the frequency of established risk factors in breast carcinoma patients and furthermore to compare the findings between premenopausal and postmenopausal women in Pakistan. A 6 months (from July 2012 to Dec 2012) cross sectional survey was conducted in Surgical and Oncology Units of Civil Hospital, Karachi. Data were collected though a well developed questionnaire from 105 female patients diagnosed with carcinoma of breast and analyzed using SPSS version 17. Institutional ethical approval was obtained prior to data collection. Out of 105 patients, 43 were premenopausal and 62 were postmenopausal, 99 being married. Mean age at diagnosis was 47.8 ± 12.4 years. A painless lump was the most frequent symptom, notived by 77.1%(n=81). Some 55.2% (n=58) patients had a lump in the right breast and 44.8%(n=47) in the left breast. In the majority of cases, the lump was present in upper outer quadrant 41.9% (n=44). Mean period of delay from appearance of symptoms to consulting a doctor was 5.13 ± 4.8 months, from the shortest 1 month to the longest 36 months. Long delay (> 3 months) was the most frequent figure 41.9%. Considering overall risk factors most frequent were first pregnancy after 20 years of age (41%), physical breast trauma (28.6%), lack of breast feeding(21.9%), and early menarche <11 years (19%), followed by null parity (16.2%), consumption of high fat diet (15.2%), family history of breast cancer or any other cancer in first degree relatives (9.5% and 13

Breast Angiosarcoma: Case Series and Expression of Vascular Endothelial Growth Factor

PubMed Central

Brar, Rondeep; West, Robert; Witten, Daniela; Raman, Bhargav; Jacobs, Charlotte; Ganjoo, Kristen

2009-01-01

Purpose Angiosarcoma of the breast is a rare, malignant tumor for which little is known regarding prognostic indicators and optimal therapeutic regimens. To address this issue, we performed a retrospective analysis of breast angiosarcoma cases seen at Stanford University along with immunohistochemical analysis for markers of angiogenesis. Methods Breast angiosarcoma cases seen between 1980 and 2008 were examined. Viable tissue blocks were analyzed for expression of vascular endothelial growth factor and its receptors. Results A total of 16 cases were identified. Data was collected regarding epidemiology, treatment, response rates, disease-free survival, and the use of various imaging modalities. Five tissue blocks remained viable for immunohistochemical analysis. Vascular endothelial growth factor-A was positively expressed in 3 of these samples. Conclusion Angiosarcoma of the breast is an aggressive malignancy with a propensity for both local recurrence and distant metastases. Angiogenesis inhibition may represent a novel therapeutic modality in this rare, vascular malignancy. PMID:20737044

Mena invasive (MenaINV) promotes multicellular streaming motility and transendothelial migration in a mouse model of breast cancer.

PubMed

Roussos, Evanthia T; Balsamo, Michele; Alford, Shannon K; Wyckoff, Jeffrey B; Gligorijevic, Bojana; Wang, Yarong; Pozzuto, Maria; Stobezki, Robert; Goswami, Sumanta; Segall, Jeffrey E; Lauffenburger, Douglas A; Bresnick, Anne R; Gertler, Frank B; Condeelis, John S

2011-07-01

We have shown previously that distinct Mena isoforms are expressed in invasive and migratory tumor cells in vivo and that the invasion isoform (Mena(INV)) potentiates carcinoma cell metastasis in murine models of breast cancer. However, the specific step of metastatic progression affected by this isoform and the effects on metastasis of the Mena11a isoform, expressed in primary tumor cells, are largely unknown. Here, we provide evidence that elevated Mena(INV) increases coordinated streaming motility, and enhances transendothelial migration and intravasation of tumor cells. We demonstrate that promotion of these early stages of metastasis by Mena(INV) is dependent on a macrophage-tumor cell paracrine loop. Our studies also show that increased Mena11a expression correlates with decreased expression of colony-stimulating factor 1 and a dramatically decreased ability to participate in paracrine-mediated invasion and intravasation. Our results illustrate the importance of paracrine-mediated cell streaming and intravasation on tumor cell dissemination, and demonstrate that the relative abundance of Mena(INV) and Mena11a helps to regulate these key stages of metastatic progression in breast cancer cells.

Suppression of MIM by microRNA-182 activates RhoA and promotes breast cancer metastasis.

PubMed

Lei, R; Tang, J; Zhuang, X; Deng, R; Li, G; Yu, J; Liang, Y; Xiao, J; Wang, H-Y; Yang, Q; Hu, G

2014-03-06

Breast cancer is the most common type of cancer among women worldwide, and metastasis represents the most devastating stage of the disease. Recent studies have revealed that microRNAs (miRNA) have critical roles to regulate cancer cell invasion and metastasis. Here we present evidence to show the role of miR-182 in breast cancer metastasis. miR-182 is upregulated in the malignant cell line variants of both human MCF10 and mouse 4T1 series. Ectopic expression of miR-182 enhanced breast cancer cell motility and invasiveness, whereas miR-182 inhibition resulted in opposite changes. In nude mice, miR-182 led to increased pulmonary colonization of cancer cells. We further demonstrated that miR-182 directly targets MIM (Missing in Metastasis), which suppresses metastasis by inhibiting ras homolog family member A (RhoA) activity and stress fiber formation in breast cancer cells. Restoring MIM expression completely blocked the pro-metastasis function of miR-182, while RhoA inhibition reversed the phenotypes of both miR-182 overexpression and MIM knockdown. In breast tumor samples, miR-182 induction is linked to downregulation of MIM, RhoA activation and poor prognosis. Hence, our data delineates the molecular pathway by which miR-182 promotes breast cancer invasion and metastasis, and may have important implication for the treatment of metastatic cancers.

A case-control study on risk factors of breast cancer in Han Chinese women.

PubMed

Liu, Li-Yuan; Wang, Fei; Cui, Shu-De; Tian, Fu-Guo; Fan, Zhi-Min; Geng, Cui-Zhi; Cao, Xu-Chen; Yang, Zhen-Lin; Wang, Xiang; Liang, Hong; Wang, Shu; Jiang, Hong-Chuan; Duan, Xue-Ning; Wang, Hai-Bo; Li, Guo-Lou; Wang, Qi-Tang; Zhang, Jian-Guo; Jin, Feng; Tang, Jin-Hai; Li, Liang; Zhu, Shi-Guang; Zuo, Wen-Shu; Yu, Li-Xiang; Xiang, Yu-Juan; Zhou, Fei; Li, Liang; Zhang, Qiang; Fu, Qin-Ye; Ma, Zhong-Bing; Gao, De-Zong; Li, Yu-Yang; Liu, Lu; Ye, Chun-Miao; Wang, Yong-Jiu; Zhou, Wen-Zhong; Yu, Zhi-Gang

2017-11-14

This study aimed to investigate risk factors associated with breast cancer among Han Chinese women in northern and eastern China. A matched case-control study involving 1489 patients with breast cancer and 1489 controls was conducted across 21 hospitals in 11 provinces in China, from April 2012 to April 2013. We developed a structured questionnaire to record information from face-to-face interviews with participants. Student's t-tests, Pearson's chi-square tests, and univariate and multivariate conditional logistic regression analyses were used to identify variables with significant differences between the case and control groups. Ten variables were identified (P < 0.05): location, economic status, waist-to-hip ratio, menopause, family history of breast cancer, present life satisfaction, sleep satisfaction, milk products, behavior prevention scores, and awareness of breast cancer. We identified a comprehensive range of factors related to breast cancer, among which several manageable factors may contribute to breast cancer prevention. Further prospective studies concerning psychological interventions, sleep regulation, health guidance, and physical exercise are required. A screening model for high-risk populations should be put on the agenda.

Analysis of Trends and Factors in Breast Multiple Primary Malignant Neoplasms

PubMed Central

Motuzyuk, Igor; Sydorchuk, Oleg; Kovtun, Natalia; Palian, Zinaida; Kostiuchenko, Yevhenii

2018-01-01

Background: The study aims to evaluate the current state and tendencies in multiple primary breast cancer incidence, behavior, and treatment in Ukraine. Methods: A total of 2032 patients who received special treatment at the Department of Breast Tumors and Reconstructive Surgery of the National Cancer Institute from 2008 to 2015 were included in the study. Among them, there were 195 patients with multiple primary malignant neoplasms: 54.9% patients with synchronous cancer and 45.1% patients with metachronous cancer. The average age of patients was 46.6 years, and the percentage of postmenopausal women was 63.1%. Among patients with synchronous cancer, there were 56.1% patients with only breast localizations and 43.9% with combination of breast and other localizations, and among patients with metachronous cancer, there were 46.6% patients with only breast localizations and 53.4% with combination of breast and other localizations. All the patients were evaluated in terms of aggressiveness of the disease, survival rates, as well as risk factors and treatment options. Results: A more aggressive course of breast cancer is observed in patients exposed to radiation from the Chernobyl accident under the age of 30 years (P < .01). The clinical course of disease in patients with synchronous cancer is worse and prognostically unfavorable compared with metachronous cancer (P < .01). The course of the disease in patients who underwent mastectomy is worse compared with patients who underwent breast-conserving surgery (P < .01). Plastic and reconstructive surgery in patients with synchronous cancer was proven to be reasonable in terms of increase in survival (P < .01). Conclusions: The patients with multiple primary breast cancer should have attentive management and treatment. Multidisciplinary team should concern all the risk factors and provide the most sufficient option of management. This is crucial to continue research in this oncological area. PMID

Obesity and menopause modify the epigenomic profile of breast cancer.

PubMed

Crujeiras, Ana B; Diaz-Lagares, Angel; Stefansson, Olafur A; Macias-Gonzalez, Manuel; Sandoval, Juan; Cueva, Juan; Lopez-Lopez, Rafael; Moran, Sebastian; Jonasson, Jon G; Tryggvadottir, Laufey; Olafsdottir, Elinborg; Tinahones, Francisco J; Carreira, Marcos C; Casanueva, Felipe F; Esteller, Manel

2017-07-01

Obesity is a high risk factor for breast cancer. This relationship could be marked by a specific methylome. The current work was aimed to explore the impact of obesity and menopausal status on variation in breast cancer methylomes. Data from Infinium 450K array-based methylomes of 64 breast tumors were coupled with information on BMI and menopausal status. Additionally, DNA methylation results were validated in 18 non-tumor and 81 tumor breast samples. Breast tumors arising in either pre- or postmenopausal women stratified by BMI or menopausal status alone were not associated with a specific DNA methylation pattern. Intriguingly, the DNA methylation pattern identified in association with the high-risk group (postmenopausal women with high BMI (>25) and premenopausal women with normal or low BMI < 25) exclusively characterized by hypermethylation of 1287 CpG sites as compared with the low-risk group. These CpG sites included the promoter region of fourteen protein-coding genes of which CpG methylation over the ZNF577 promoter region represents the top scoring associated event. In an independent cohort, the ZNF577 promoter methylation remained statistically significant in association with the high-risk group. Additionally, the impact of ZNF577 promoter methylation on mRNA expression levels was demonstrated in breast cancer cell lines after treatment with a demethylating agent (5-azacytidine). In conclusion, the epigenome of breast tumors is affected by a complex interaction between BMI and menopausal status. The ZNF577 methylation quantification is clearly relevant for the development of novel biomarkers of precision therapy in breast cancer. © 2017 Society for Endocrinology.

Modulation of oncogenic transcription factors by bioactive natural products in breast cancer.

PubMed

Hasanpourghadi, Mohadeseh; Pandurangan, Ashok Kumar; Mustafa, Mohd Rais

2018-02-01

Carcinogenesis, a multi-step phenomenon, characterized by alterations at genetic level and affecting the main intracellular pathways controlling cell growth and development. There are growing number of evidences linking oncogenes to the induction of malignancies, especially breast cancer. Modulations of oncogenes lead to gain-of-function signals in the cells and contribute to the tumorigenic phenotype. These signals yield a large number of proteins that cause cell growth and inhibit apoptosis. Transcription factors such as STAT, p53, NF-κB, c-JUN and FOXM1, are proteins that are conserved among species, accumulate in the nucleus, bind to DNA and regulate the specific genes targets. Oncogenic transcription factors resulting from the mutation or overexpression following aberrant gene expression relay the signals in the nucleus and disrupt the transcription pattern. Activation of oncogenic transcription factors is associated with control of cell cycle, apoptosis, migration and cell differentiation. Among different cancer types, breast cancer is one of top ten cancers worldwide. There are different subtypes of breast cancer cell-lines such as non-aggressive MCF-7 and aggressive and metastatic MDA-MB-231 cells, which are identified with distinct molecular profile and different levels of oncogenic transcription factor. For instance, MDA-MB-231 carries mutated and overexpressed p53 with its abnormal, uncontrolled downstream signalling pathway that account for resistance to several anticancer drugs compared to MCF-7 cells with wild-type p53. Appropriate enough, inhibition of oncogenic transcription factors has become a potential target in discovery and development of anti-tumour drugs against breast cancer. Plants produce diverse amount of organic metabolites. Universally, these metabolites with biological activities are known as "natural products". The chemical structure and function of natural products have been studied since 1850s. Investigating these properties leaded

HSPC159 promotes proliferation and metastasis via inducing EMT and activating PI3K/Akt pathway in breast cancer.

PubMed

Zheng, Jie; Zhang, Mengxue; Zhang, Liying; Ding, Xiaodi; Li, Wentong; Lu, Shijun

2018-05-08

HSPC159 is a novel human galectin-related protein and has been shown to involved in the carcinogenesis. Little is known about HSPC159 expression and function in breast cancer. Here we showed that HSPC159 was aberrantly expressed in both breast cancer cell lines and tumor tissues and that its expression was associated with poor prognosis of breast cancer patients. Using gain- and loss-of-function methods we found that HSPC159 enhanced breast cancer cells proliferation and metastasis in vitro and in vivo. Mechanistically, HSPC159 was found to induce epithelial-mesenchymal transition (EMT) and F-actin polymerization process of breast cancer cells. Moreover, HSPC159 promoted proliferation, migration and invasion through activating PI3K/Akt signaling pathway in breast cancer. In conclusion, our findings demonstrated that HSPC159 contributed to breast cancer progression via PI3K/Akt pathway and might serve as a potential therapeutic target for the treatment of breast cancer. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Do socioeconomic factors influence breast cancer screening practices among Arab women in Qatar?

PubMed

Donnelly, Tam Truong; Al Khater, Al-Hareth; Al Kuwari, Mohamed Ghaith; Al-Bader, Salha Bujassoum; Al-Meer, Nabila; Abdulmalik, Mariam; Singh, Rajvir; Chaudhry, Sofia; Fung, Tak

2015-01-22

Breast cancer incidence rates are rising in Qatar. Although the Qatari government provides subsidised healthcare and screening programmes that reduce cost barriers for residents, breast cancer screening (BCS) practices among women remain low. This study explores the influence of socioeconomic status on BCS among Arab women in Qatar. A multicentre, cross-sectional quantitative survey was conducted with 1063 Arab women (87.5% response rate) in Qatar from March 2011 to July 2011. Women who were 35 years or older and had lived in Qatar for at least 10 years were recruited from seven primary healthcare centres and women's health clinics in urban and semiurban regions of Qatar. Associations between socioeconomic factors and BCS practice were estimated using χ(2) tests and multivariate logistic regression analyses. Findings indicate that less than one-third of the participants practised BCS appropriately, whereas less than half of the participants were familiar with recent BCS guidelines. Married women and women with higher education and income levels were significantly more likely to be aware of and to practise BCS than women who had lower education and income levels. Findings indicate low levels of awareness and low participation rates in BCS among Arab women in Qatar. Socioeconomic factors influence these women's participation in BCS activities. The strongest predictors for BCS practice are higher education and higher income levels. Additional research is needed to explore the impact of economic factors on healthcare seeking behaviours in the Middle Eastern countries that have a high national gross domestic product where healthcare services are free or heavily subsidised by the government; promotion of BCS and intervention strategies in these countries should focus on raising awareness about breast cancer, the cost and benefit of early screening for this disease, particularly among low-income women. Published by the BMJ Publishing Group Limited. For permission to

[Correlation of insulin-like growth factor-1 (IGF-1) to angiogenesis of breast cancer in IGF-1-deficient mice].

PubMed

Tang, Hong-Bo; Ren, Yu-Ping; Zhang, Jun; Ma, Shi-Hui; Gao, Feng; Wu, Yi-Ping

2007-11-01

Insulin-like growth factors (IGFs) play important roles in the development and progression of tumors. But the mechanism of tumorigenesis in relation to IGF-1 is unclear yet. This study was to explore the correlation of circulating IGF-1 level to the angiogenesis of breast cancer in IGF-1-deficient mice. The liver-specific IGF-1-deficient (LID) mice and control mice were injected with 7,12-dimethybenz(a)anthracene (DMBA) to develop breast cancer. Ginsenoside Rg3 was used to intervene tumor growth. The occurrence rates of breast cancer were compared. The expression of vascular endothelial growth factor (VEGF) and microvessel density (MVD) was detected by immunohistochemistry. The occurrence rate of breast cancer was 66.67% in untreated control mice, 33.33% in untreated LID mice, 36.00% in Rg3-treated control mice, and 12.00% in Rg3-treated LID mice. The tumor size was (0.79+/-0.20) cm in untreated control mice, (0.37+/-0.08) cm in untreated LID mice, (0.32+/-0.08) cm in Rg3-treated control mice, and (0.15+/-0.05) cm in Rg3-treated LID mice. The average light density and positive rate of VEGF were the highest in untreated control mice (0.34+/-0.10 and 0.04+/-0.02, P<0.05), and the lowest in Rg3-treated LID mice (0.13+/-0.03 and 0.01+/-0.00, P<0.05). The MVD was 31.9+/-5.3 in untreated control mice, 26.8+/-4.9 in untreated LID mice, 20.1+/-4.9 in Rg3-treated control mice, and 14.4+/-4.9 in Rg3-treated LID mice. Circulating IGF-1 plays a role in the onset and development of breast cancer. Degrading serum IGF-1 level could inhibit angiogenesis and growth of breast cancer. Rg3 could promote this effect.

Young adult breast cancer patients have a poor prognosis independent of prognostic clinicopathological factors: a study from the Japanese Breast Cancer Registry.

PubMed

Kataoka, Akemi; Iwamoto, Takayuki; Tokunaga, Eriko; Tomotaki, Ai; Kumamaru, Hiraku; Miyata, Hiroaki; Niikura, Naoki; Kawai, Masaaki; Anan, Keisei; Hayashi, Naoki; Masuda, Shinobu; Tsugawa, Koichiro; Aogi, Kenjiro; Ishida, Takanori; Masuoka, Hideji; Iijima, Kotaro; Kinoshita, Takayuki; Nakamura, Seigo; Tokuda, Yutaka

2016-11-01

The aim of this study was to investigate whether young age at onset of breast cancer is an independent prognostic factor in patients from the Japanese Breast Cancer Registry, after adjustment of known clinicopathological prognostic factors. Of the 53,670 patients registered between 2004 and 2006 and surveyed after a 5-year follow-up prognosis, 25,898 breast cancer patients (48.3 %), who were obtained prognostic data, were examined. Clinicopathological factors were compared between young adult (YA; <35 years), middle-aged adult (MA; 35-50 years), and older adult (OA; >50 years) patients. Five-year disease-free survival (DFS) and overall survival (OS) rates were studied. YA patients were associated with an advanced TNM stage and aggressive characteristics (e.g. human epidermal growth factor receptor 2 (HER2)-positive or oestrogen receptor (ER)-negative breast cancers) compared to MA and OA patients (P < 0.001). The 5-year DFS and OS rates were 79.4 % and 90.8, 88.5 and 95.0 %, and 87.8 % and 91.6 % for YA, MA, and OA patients, respectively. From the multivariable regression analysis, young age at onset was confirmed as an independent prognostic factor for both DFS (hazard ratio 1.73, 95 % confidence interval 1.42-2.10; P < 0.001) and OS (hazard ratio 1.58, 95 % confidence interval 1.16-2.15; P = 0.004). Young age at onset is an independent negative prognostic factor in breast cancer. Further studies are required to develop new therapeutic strategies for YA breast cancer patients.

Insulin, insulin-like growth factor-I and breast cancer risk in Japanese women.

PubMed

Hirose, Kaoru; Toyama, Tatsuya; Iwata, Hiroji; Takezaki, Toshiro; Hamajima, Nobuyuki; Tajima, Kazuo

2003-01-01

To evaluate the effects of glucose metabolism related factors, such as insulin and insulin-like growth-factors (IGFs), on breast cancer development among Japanese women, we conducted a case-referent study comparing 187 women presenting with operable breast cancer and 190 women of the same age having no breast cancer. Odds ratios (OR) and 95% confidence intervals (95%CI) were determined by multiple logistic regression analysis. In the present study, no association in risk was observed with increasing levels of IGF-I or IGF binding protein-3 (IGFBP-3), before or after adjustment these factors. However, a suggestion of a positive association of an increased breast cancer risk was evident in postmenopausal women with elevated plasma insulin levels, particularly those with BMI>23.07. The OR for plasma insulin in the top tertile was 4.48 (95%CI:1.07-18.7) compared to the bottom tertile. For C-peptide, there was a similar positive association, with a corresponding OR of 2.28. In addition, we observed strong links between plasma insulin, C-peptide levels and estrogen receptor (ER) negative breast cancer, with ORs of 2.79(95%CI:1.09-7.16), and 2.52 (95%CI:0.91-6.97) respectively, for the top versus bottom tertiles. In conclusion, the present study suggested that plasma insulin level is a predictor of postmenopausal breast cancer in obese women and ER negative breast cancer. Additional studies are needed to clarify the role of glucose metabolism pathways in breast cancer development and interaction of IGF systems.

Breast cancer risk factors and HER2 over-expression in tumors.

PubMed

Swede, H; Moysich, K B; Freudenheim, J L; Quirk, J T; Muti, P C; Hurd, T C; Edge, S B; Winston, J S; Michalek, A M

2001-01-01

Few epidemiologic studies have investigated the potential role of HER2 in the etiology of breast cancer. We conducted a case-case study of 156 women with incident, invasive ductal carcinoma. Multivariate unconditional logistic regression was used to estimate the odds ratios for a HER2 positive tumor in relation to known and putative risk factors of breast cancer. HER2 status was detected by immunohistochemistry on archival tissue. HER2 positive breast cancers tended to be larger and were less likely to express estrogen receptors, and the incidence rate was higher in patients less than 40 years old. We observed an association between a self-reported history of benign breast disease and the occurrence of HER2 positive breast cancer (OR, 2.1;95% CI, 1.1-4.1). We did not detect associations between HER2 over-expression and family history of breast cancer, parity, late age at first birth, ever having breast fed an infant, or oral contraceptive use. Our findings merit consideration in light of recent evidence of HER2 amplification or over-expression in benign breast disease. Should the link to breast cancer be established, HER2 positive benign breast disease could potentially serve as an early marker for preventive intervention.

Nitrophenols isolated from diesel exhaust particles promote the growth of MCF-7 breast adenocarcinoma cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Furuta, Chie; Laboratory of Veterinary Physiology, Department of Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and Technology, Tokyo 183-8509; Suzuki, Akira K.

2008-08-01

Diesel exhaust particles (DEPs) cause many adverse health problems, and reports indicate increased risk of breast cancer in men and women through exposure to gasoline and vehicle exhaust. However, DEPs include vast numbers of compounds, and the specific compound(s) responsible for these actions are not clear. We recently isolated two nitrophenols from DEPs-3-methyl-4-nitrophenol (4-nitro-m-cresol; PNMC) and 4-nitro-3-phenylphenol (PNMPP)-and showed that they had estrogenic and anti-androgenic activities. Here, we tried to clarify the involvement of these two nitrophenols in promoting the growth of the MCF-7 breast cancer cell line. First, comet assay was used to detect the genotoxicity of PNMC andmore » PNMPP in a CHO cell line. At all doses tested, PNMC and PNMPP showed negative genotoxicity, indicating that they had no tumor initiating activity. Next, the estrogen-responsive breast cancer cell line MCF-7 was used to assess cell proliferation. Proliferation of MCF-7 cells was stimulated by PNMC, PNMPP, and estradiol-17{beta} and the anti-estrogens 4-hydroxytamoxifen and ICI 182,780 inhibited the proliferation. To further investigate transcriptional activity through the estrogen receptor, MCF-7 cells were transfected with a receptor gene that allowed expression of luciferase enzyme under the control of the estrogen regulatory element. PNMC and PNMPP induced luciferase activity in a dose-dependent manner at submicromolar concentrations. ICI 182,780 inhibited the luciferase activity induced by PNMC and PNMPP. These results clearly indicate that PNMC and PNMPP do not show genotoxicity but act as tumor promoters in an estrogen receptor {alpha}-predominant breast cancer cell line.« less

Mastectomy or breast conserving surgery? Factors affecting type of surgical treatment for breast cancer--a classification tree approach.

PubMed

Martin, Michael A; Meyricke, Ramona; O'Neill, Terry; Roberts, Steven

2006-04-20

A critical choice facing breast cancer patients is which surgical treatment--mastectomy or breast conserving surgery (BCS)--is most appropriate. Several studies have investigated factors that impact the type of surgery chosen, identifying features such as place of residence, age at diagnosis, tumor size, socio-economic and racial/ethnic elements as relevant. Such assessment of "propensity" is important in understanding issues such as a reported under-utilisation of BCS among women for whom such treatment was not contraindicated. Using Western Australian (WA) data, we further examine the factors associated with the type of surgical treatment for breast cancer using a classification tree approach. This approach deals naturally with complicated interactions between factors, and so allows flexible and interpretable models for treatment choice to be built that add to the current understanding of this complex decision process. Data was extracted from the WA Cancer Registry on women diagnosed with breast cancer in WA from 1990 to 2000. Subjects' treatment preferences were predicted from covariates using both classification trees and logistic regression. Tumor size was the primary determinant of patient choice, subjects with tumors smaller than 20 mm in diameter preferring BCS. For subjects with tumors greater than 20 mm in diameter factors such as patient age, nodal status, and tumor histology become relevant as predictors of patient choice. Classification trees perform as well as logistic regression for predicting patient choice, but are much easier to interpret for clinical use. The selected tree can inform clinicians' advice to patients.

Long non-coding RNA MIAT promotes breast cancer progression and functions as ceRNA to regulate DUSP7 expression by sponging miR-155-5p.

PubMed

Luan, Tian; Zhang, Ximei; Wang, Shuyuan; Song, Yan; Zhou, Shunheng; Lin, Jing; An, Weiwei; Yuan, Weiguang; Yang, Yue; Cai, Huilong; Zhang, Qingyuan; Wang, Lihong

2017-09-29

Long non-coding RNAs (lncRNA) have been reported as key regulators in the progression and metastasis of breast cancer. In this study, we found that the lncRNA myocardial infarction associated transcript (MIAT) expression was upregulated in breast cancer in The Cancer Genome Atlas (TCGA) data sets. We validated that MIAT was higher in breast cancer cell lines and advanced breast tumors than in normal controls. And MIAT overexpression associated with TNM stage and lymphnode metastasis. Knockdown MIAT inhibited breast cancer cell proliferation and promoted apoptosis. Also MIAT downregulation suppressed epithelial-mesenchymal transition (EMT) and decreased migration and invasion in MDA-MB-231 and MCF-7 breast cancer cell lines. More importantly, knockdown MIAT inhibited tumor growth in vivo . Our results suggested that MIAT acted as a competing endogenous RNA (ceRNA) to regulate the expression of dual specificity phosphatase 7 (DUSP7) by taking up miR-155-5p in breast cancer. There were positive correlation between MIAT and DUSP7 expression in breast cancer patients. We conclude that MIAT promotes breast cancer progression and functions as ceRNA to regulate DUSP7 expression by sponging miR-155-5p in breast cancer.

Human Adipose-Derived Mesenchymal Stem Cell-Secreted CXCL1 and CXCL8 Facilitate Breast Tumor Growth By Promoting Angiogenesis.

PubMed

Wang, Yuan; Liu, Junli; Jiang, Qingyuan; Deng, Jie; Xu, Fen; Chen, Xiaolei; Cheng, Fuyi; Zhang, Yujing; Yao, Yunqi; Xia, Zhemin; Xu, Xia; Su, Xiaolan; Huang, Meijuan; Dai, Lei; Yang, Yang; Zhang, Shuang; Yu, Dechao; Zhao, Robert Chunhua; Wei, Yuquan; Deng, Hongxin

2017-09-01

Autologous adipose tissue or adipose tissue with additive adipose-derived mesenchymal stem cells (ADSCs) is used in the breast reconstruction of breast cancer patients who undergo mastectomy. ADSCs play an important role in the angiogenesis and adipogenesis, which make it much better than other materials. However, ADSCs may promote residual tumor cells to proliferate or metastasize, and the mechanism is still not fully understood. In this study, we demonstrated that human ADSCs (hADSCs) could facilitate tumor cells growth after co-injection with MCF7 and ZR-75-30 breast cancer cells (BCCs) by promoting angiogenesis, but hADSCs showed limited effect on the growth of MDA-MB-231 BCCs. Intriguingly, compared with ZR-75-30 tumor cells, MCF7 tumor cells were more potentially promoted by hADSCs in the aspects of angiogenesis and proliferation. Consistent with this, cytokine and angiogenesis array analyses showed that after co-injection with hADSCs, the CXCL1 and CXCL8 concentration were significantly increased in MCF7 tumor, but only moderately increased in ZR-75-30 tumor and did not increase in MDA-MB-231 tumor. Furthermore, we found that CXCL1/8 were mainly derived from hADSCs and could increase the migration and tube formation of human umbilical vein endothelial cells (HUVECs) by signaling via their receptors CXCR1 and CXCR2. A CXCR1/2-specific antagonist (SCH527123) attenuated the angiogenesis and tumor growth in vivo. Our findings suggest that CXCL1/8 secreted by hADSCs could promote breast cancer angiogenesis and therefore provide better understanding of safety concerns regarding the clinical application of hADSCs and suggestion in further novel therapeutic options. Stem Cells 2017;35:2060-2070. © 2017 AlphaMed Press.

A novel duplication polymorphism in the FANCA promoter and its association with breast and ovarian cancer.

PubMed

Thompson, Ella; Dragovic, Rebecca L; Stephenson, Sally-Anne; Eccles, Diana M; Campbell, Ian G; Dobrovic, Alexander

2005-04-29

The FANCA gene is one of the genes in which mutations lead to Fanconi anaemia, a rare autosomal recessive disorder characterised by congenital abnormalities, bone marrow failure, and predisposition to malignancy. FANCA is also a potential breast and ovarian cancer susceptibility gene. A novel allele was identified which has a tandem duplication of a 13 base pair sequence in the promoter region. We screened germline DNA from 352 breast cancer patients, 390 ovarian cancer patients and 256 normal controls to determine if the presence of either of these two alleles was associated with an increased risk of breast or ovarian cancer. The duplication allele had a frequency of 0.34 in the normal controls. There was a non-significant decrease in the frequency of the duplication allele in breast cancer patients. The frequency of the duplication allele was significantly decreased in ovarian cancer patients. However, when malignant and benign tumours were considered separately, the decrease was only significant in benign tumours. The allele with the tandem duplication does not appear to modify breast cancer risk but may act as a low penetrance protective allele for ovarian cancer.

A novel duplication polymorphism in the FANCA promoter and its association with breast and ovarian cancer

PubMed Central

Thompson, Ella; Dragovic, Rebecca L; Stephenson, Sally-Anne; Eccles, Diana M; Campbell, Ian G; Dobrovic, Alexander

2005-01-01

The FANCA gene is one of the genes in which mutations lead to Fanconi anaemia, a rare autosomal recessive disorder characterised by congenital abnormalities, bone marrow failure, and predisposition to malignancy. FANCA is also a potential breast and ovarian cancer susceptibility gene. A novel allele was identified which has a tandem duplication of a 13 base pair sequence in the promoter region. Methods We screened germline DNA from 352 breast cancer patients, 390 ovarian cancer patients and 256 normal controls to determine if the presence of either of these two alleles was associated with an increased risk of breast or ovarian cancer. Results The duplication allele had a frequency of 0.34 in the normal controls. There was a non-significant decrease in the frequency of the duplication allele in breast cancer patients. The frequency of the duplication allele was significantly decreased in ovarian cancer patients. However, when malignant and benign tumours were considered separately, the decrease was only significant in benign tumours. Conclusion The allele with the tandem duplication does not appear to modify breast cancer risk but may act as a low penetrance protective allele for ovarian cancer. PMID:15860134

Regulation of anti-apoptotic signaling by Kruppel-like factors 4 and 5 mediates lapatinib resistance in breast cancer

PubMed Central

Farrugia, M K; Sharma, S B; Lin, C-C; McLaughlin, S L; Vanderbilt, D B; Ammer, A G; Salkeni, M A; Stoilov, P; Agazie, Y M; Creighton, C J; Ruppert, J M

2015-01-01

The Kruppel-like transcription factors (KLFs) 4 and 5 (KLF4/5) are coexpressed in mouse embryonic stem cells, where they function redundantly to maintain pluripotency. In mammary carcinoma, KLF4/5 can each impact the malignant phenotype, but potential linkages to drug resistance remain unclear. In primary human breast cancers, we observed a positive correlation between KLF4/5 transcript abundance, particularly in the human epidermal growth factor receptor 2 (HER2)-enriched subtype. Furthermore, KLF4/5 protein was rapidly upregulated in human breast cancer cells following treatment with the HER2/epidermal growth factor receptor inhibitor, lapatinib. In addition, we observed a positive correlation between these factors in the primary tumors of genetically engineered mouse models (GEMMs). In particular, the levels of both factors were enriched in the basal-like tumors of the C3(1) TAg (SV40 large T antigen transgenic mice under control of the C3(1)/prostatein promoter) GEMM. Using tumor cells derived from this model as well as human breast cancer cells, suppression of KLF4 and/or KLF5 sensitized HER2-overexpressing cells to lapatinib. Indicating cooperativity, greater effects were observed when both genes were depleted. KLF4/5-deficient cells had reduced basal mRNA and protein levels of the anti-apoptotic factors myeloid cell leukemia 1 (MCL1) and B-cell lymphoma-extra large (BCL-XL). Moreover, MCL1 was upregulated by lapatinib in a KLF4/5-dependent manner, and enforced expression of MCL1 in KLF4/5-deficient cells restored drug resistance. In addition, combined suppression of KLF4/5 in cultured tumor cells additively inhibited anchorage-independent growth, resistance to anoikis and tumor formation in immunocompromised mice. Consistent with their cooperative role in drug resistance and other malignant properties, KLF4/5 levels selectively stratified human HER2-enriched breast cancer by distant metastasis-free survival. These results identify KLF4 and KLF5 as

Long noncoding RNA linc00617 exhibits oncogenic activity in breast cancer.

PubMed

Li, Hengyu; Zhu, Li; Xu, Lu; Qin, Keyu; Liu, Chaoqian; Yu, Yue; Su, Dongwei; Wu, Kainan; Sheng, Yuan

2017-01-01

Protein-coding genes account for only 2% of the human genome, whereas the vast majority of transcripts are noncoding RNAs including long noncoding RNAs. LncRNAs are involved in the regulation of a diverse array of biological processes, including cancer progression. An evolutionarily conserved lncRNA TUNA, was found to be required for pluripotency of mouse embryonic stem cells. In this study, we found the human ortholog of TUNA, linc00617, was upregulated in breast cancer samples. Linc00617 promoted motility and invasion of breast cancer cells and induced epithelial-mesenchymal-transition (EMT), which was accompanied by generation of stem cell properties. Moreover, knockdown of linc00617 repressed lung metastasis in vivo. We demonstrated that linc00617 upregulated the expression of stemness factor Sox2 in breast cancer cells, which was shown to promote the oncogenic activity of breast cancer cells by stimulating epithelial-to-mesenchymal transition and enhancing the tumor-initiating capacity. Thus, our data indicate that linc00617 functions as an important regulator of EMT and promotes breast cancer progression and metastasis via activating the transcription of Sox2. Together, it suggests that linc00617 may be a potential therapeutic target for aggressive breast cancer. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Breast density and parenchymal texture measures as potential risk factors for estrogen-receptor positive breast cancer

NASA Astrophysics Data System (ADS)

Keller, Brad M.; Chen, Jinbo; Conant, Emily F.; Kontos, Despina

2014-03-01

Accurate assessment of a woman's risk to develop specific subtypes of breast cancer is critical for appropriate utilization of chemopreventative measures, such as with tamoxifen in preventing estrogen-receptor positive breast cancer. In this context, we investigate quantitative measures of breast density and parenchymal texture, measures of glandular tissue content and tissue structure, as risk factors for estrogen-receptor positive (ER+) breast cancer. Mediolateral oblique (MLO) view digital mammograms of the contralateral breast from 106 women with unilateral invasive breast cancer were retrospectively analyzed. Breast density and parenchymal texture were analyzed via fully-automated software. Logistic regression with feature selection and was performed to predict ER+ versus ER- cancer status. A combined model considering all imaging measures extracted was compared to baseline models consisting of density-alone and texture-alone features. Area under the curve (AUC) of the receiver operating characteristic (ROC) and Delong's test were used to compare the models' discriminatory capacity for receptor status. The density-alone model had a discriminatory capacity of 0.62 AUC (p=0.05). The texture-alone model had a higher discriminatory capacity of 0.70 AUC (p=0.001), which was not significantly different compared to the density-alone model (p=0.37). In contrast the combined density-texture logistic regression model had a discriminatory capacity of 0.82 AUC (p<0.001), which was statistically significantly higher than both the density-alone (p<0.001) and texture-alone regression models (p=0.04). The combination of breast density and texture measures may have the potential to identify women specifically at risk for estrogen-receptor positive breast cancer and could be useful in triaging women into appropriate risk-reduction strategies.

[Breast feeding rates and factors influencing breast feeding practice in late preterm infants: comparison with preterm born at less than 34 weeks of gestational age].

PubMed

Jang, Gun Ja; Lee, Sang Lak; Kim, Hyeon Mi

2012-04-01

This study was done to compare breast feeding rates and factors influencing feeding practice between late preterm (34 ≤ GA < 37) and preterm infants (GA<34). A survey was done of 207 late preterm and 117 preterm infants in neonatal intensive care units (NICU) of 4 university hospitals in D city. Data were collected from July 2009 to June 2010 from 324 medical records in the NICU. Breast-feeding at home was checked either by telephone survey or questioning during hospital visits. Rate of breast feeding for late preterm infants was significantly lower than for preterm infants. There was no significant difference in breast-feeding at home. We found differences in factors influencing breast feeding between the two groups. Factors influencing feeding for late preterm infants were type of delivery, mothers' occupation, feeding type during hospitalization, time elapse from hospital discharge, total admission days, infant's body weight at first feeding and length of NPO (nothing by mouth). Factors influencing feeding for preterm infants were birth order, maternal disease and obstetric complications, and one-minute Apgar score. Results of the study show low rates of breast-feeding for late preterm infants indicating a need for breast-feeding education for mothers of these infants.

The association between different night shiftwork factors and breast cancer: a case–control study

PubMed Central

Fritschi, L; Erren, T C; Glass, D C; Girschik, J; Thomson, A K; Saunders, C; Boyle, T; El-Zaemey, S; Rogers, P; Peters, S; Slevin, T; D'Orsogna, A; de Vocht, F; Vermeulen, R; Heyworth, J S

2013-01-01

Background: Research on the possible association between shiftwork and breast cancer is complicated because there are many different shiftwork factors, which might be involved including: light at night, phase shift, sleep disruption and changes in lifestyle factors while on shiftwork (diet, physical activity, alcohol intake and low sun exposure). Methods: We conducted a population-based case–control study in Western Australia from 2009 to 2011 with 1205 incident breast cancer cases and 1789 frequency age-matched controls. A self-administered questionnaire was used to collect demographic, reproductive, and lifestyle factors and lifetime occupational history and a telephone interview was used to obtain further details about the shiftwork factors listed above. Results: A small increase in risk was suggested for those ever doing the graveyard shift (work between midnight and 0500 hours) and breast cancer (odds ratio (OR)=1.16, 95% confidence interval (CI)=0.97–1.39). For phase shift, we found a 22% increase in breast cancer risk (OR=1.22, 95% CI=1.01–1.47) with a statistically significant dose–response relationship (P=0.04). For the other shiftwork factors, risks were marginally elevated and not statistically significant. Conclusion: We found some evidence that some of the factors involved in shiftwork may be associated with breast cancer but the ORs were low and there were inconsistencies in duration and dose–response relationships. PMID:24022188

Depression and anxiety levels in early stage Turkish breast cancer patients and related factors.

PubMed

Dastan, Nihal Bostanci; Buzlu, Sevim

2011-01-01

Psychiatric disorders such as depression and anxiety are common among cancer patients. If left untreated, these disorders can lead to poor treatment compliance, prolonged hospital stay and reduced life quality. In this prospective study, we aimed determine anxiety and depression levels and related factors among female breast cancer patients presenting to a breast surgery clinic in Istanbul and who met the inclusion criteria. Data were collected using a questionnaire and the Hospital Anxiety and Depression Scale (HAD). The mean age was 48.2 years and the mean post-operative period was 17.9 months. It was found that 46.3 % of the patients had stage I, and 53.7 % stage II, 59.3 % of them undergoing breast conserving surgery and 40.7 % mastectomy. When evaluated according to the HAD Scale, it was found that anxiety scores of 35.1 % of the patients and depression scores of 17.1 % of the patients were higher than their cut-off points. With regard to the affecting factors, depression scores of those with no family history of breast cancer were significantly higher than those with no family history of breast cancer (t= 1.53; p= 0.03); that the depression scores of the patients who underwent mastectomy were significantly higher than those who underwent breast conserving surgery (t= 1.75; p= 0.04). Additionally, it was found that low income was an important risk factor for anxiety; whereas a history of breast cancer in the family and mastectomy was an important risk factor for depression.These results indicate the importance of determining psychiatric problems and appropriate approaches in addition to medical treatment in breast cancer patients.

Assessment of Risk Factors of Obesity and Diet on Breast Cancer in Ankara, Turkey.

PubMed

Alim, Nural Erzurum; Kiziltan, Gul

2016-01-01

To determine the risk factors of obesity and diet on breast cancer in Ankara, Turkey. A case-controlled study was carried out on newly diagnosed 40 breast cancer patients [patient group (PC)] and 40 volunteer individuals [control group (CG)] with no diagnosis of cancer and history of cancer in the family with similar characteristics to the age and gender-matched patient group between March and July 2016. All the individuals were administered a questionnaire by face-to-face interview method. The mean menarche age, age at first birth and menopause age were 13.0±1.17, 22.6±3.78 and 44.33±2.39 years in PG and 12.3±0.95, 21.6±2.99, 46.71±2.41 years in CG, respectively. The mean BMI values were determined as 28.1±6.75 kg/m 2 in PG and 30.1±6.18 kg/m 2 in CG (p>0.05). It was determined that intake of vitamin C and fiber decreases the risk of breast cancer. Also, eating quickly and smoking were risk factors for breast cancer (p<0.05). This study indicated that there are relationships between menarche age, menopause age, and age at first birth, eating quickly, smoking and breast cancer. Conversely, there are significant negative relationships between dietary fiber, vitamin C intake and breast cancer. As a result, it can be said that there is a link between breast cancer and lifestyle factors and a reduction in the risk of developing breast cancer can be achieved through changes in diet, one of the lifestyle factors.

Assessment of Risk Factors of Obesity and Diet on Breast Cancer in Ankara, Turkey

PubMed Central

Alim, Nural Erzurum; Kiziltan, Gul

2016-01-01

Objective: To determine the risk factors of obesity and diet on breast cancer in Ankara, Turkey. Methods: A case-controlled study was carried out on newly diagnosed 40 breast cancer patients [patient group (PC)] and 40 volunteer individuals [control group (CG)] with no diagnosis of cancer and history of cancer in the family with similar characteristics to the age and gender-matched patient group between March and July 2016. All the individuals were administered a questionnaire by face-to-face interview method. Results: The mean menarche age, age at first birth and menopause age were 13.0±1.17, 22.6±3.78 and 44.33±2.39 years in PG and 12.3±0.95, 21.6±2.99, 46.71±2.41 years in CG, respectively. The mean BMI values were determined as 28.1±6.75 kg/m2 in PG and 30.1±6.18 kg/m2 in CG (p>0.05). It was determined that intake of vitamin C and fiber decreases the risk of breast cancer. Also, eating quickly and smoking were risk factors for breast cancer (p<0.05). Conclusion: This study indicated that there are relationships between menarche age, menopause age, and age at first birth, eating quickly, smoking and breast cancer. Conversely, there are significant negative relationships between dietary fiber, vitamin C intake and breast cancer. As a result, it can be said that there is a link between breast cancer and lifestyle factors and a reduction in the risk of developing breast cancer can be achieved through changes in diet, one of the lifestyle factors. PMID:28083060

Policy and public health recommendations to promote the initiation and duration of breast-feeding in developed country settings.

PubMed

Dyson, Lisa; Renfrew, Mary J; McFadden, Alison; McCormick, Felicia; Herbert, Gill; Thomas, James

2010-01-01

To develop policy and public health recommendations for implementation at all levels by individuals and organisations working in, or related to, the field of breast-feeding promotion in developed country settings, where breast-feeding rates remain low. Two research phases, comprising (i) an assessment of the formal evidence base in developed country settings and (ii) a consultation with UK-based practitioners, service managers and commissioners, and representatives of service users. The evidence base included three systematic reviews and an Evidence Briefing. One hundred and ten studies evaluating an intervention in developed country settings were assessed for quality and awarded an overall quality rating. Studies with a poor quality rating were excluded. The resulting seventy studies examined twenty-five types of intervention for breast-feeding promotion. These formed the basis of the second consultation phase to develop the evidence-based interventions into recommendations for practice, which comprised (i) pilot consultation, (ii) electronic consultation, (iii) fieldwork meetings and (iv) workshops. Draft findings were synthesised for two rounds of stakeholder review conducted by the National Institute for Health and Clinical Excellence. Twenty-five recommendations emerged within three complementary and necessary categories, i.e. public health policy, mainstream clinical practice and local interventions. The need for national policy directives was clearly identified as a priority to address many of the barriers experienced by practitioners when trying to work across sectors, organisations and professional groups. Routine implementation of the WHO/UNICEF Baby Friendly Initiative across hospital and community services was recommended as core to breast-feeding promotion in the UK. A local mix of complementary interventions is also required.

Review of Factors Influencing Women's Choice of Mastectomy Versus Breast Conserving Therapy in Early Stage Breast Cancer: A Systematic Review.

PubMed

Gu, Jeffrey; Groot, Gary; Boden, Catherine; Busch, Angela; Holtslander, Lorraine; Lim, Hyun

2018-01-03

We have performed a narrative synthesis. A literature search was conducted between January 2000 and June 2014 in 7 databases. The initial search identified 2717 articles; 319 underwent abstract screening, 67 underwent full-text screening, and 25 final articles were included. This review looked at early stage breast cancer in women only, excluding ductal carcinoma in situ and advanced breast cancer. A conceptual framework was created to organize the central constructs underlying women's choices: clinicopathologic factors, physician factors, and individual factors with subgroups of sociodemographic, geographic, and personal beliefs and preferences. This framework guided our review's synthesis and analysis. We found that larger tumor size and increasing stage was associated with increased rates of mastectomy. The results for age varied, but suggested that old and young extremes of diagnostic age were associated with an increased likelihood of mastectomy. Higher socioeconomic status was associated with higher breast conservation therapy (BCT) rates. Resident rural location and increasing distance from radiation treatment facilities were associated with lower rates of BCT. Individual belief factors influencing women's choice of mastectomy (mastectomy being reassuring, avoiding radiation, an expedient treatment) differed from factors influencing choice of BCT (body image and femininity, physician recommendation, survival equivalence, less surgery). Surgeon factors, including female gender, higher case numbers, and individual surgeon practice, were associated with increased BCT rates. The decision-making process for women with early stage breast cancer is complicated and affected by multiple factors. Organizing these factors into central constructs of clinicopathologic, individual, and physician factors may aid health-care professionals to better understand this process. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Motivational factors and psychological processes in cosmetic breast augmentation surgery.

PubMed

Solvi, Anette S; Foss, Kaja; von Soest, Tilmann; Roald, Helge E; Skolleborg, Knut C; Holte, Arne

2010-04-01

We investigated how and why prospective cosmetic breast augmentation patients decide to undergo such surgery. The results can offer important insights to plastic surgeons in addressing their patients' motives and expectations, and thereby avoiding potential patient dissatisfaction and disappointment. It is also a necessary first step to better understand the increasing tendency among women in the Western society to seek cosmetic breast augmentation. A qualitative, descriptive and phenomenological design was employed. Fourteen female prospective breast augmentation patients, aged 19-46 years, were recruited from a private plastic surgery clinic and interviewed in depth based on an informant-centred format. The interviews were tape-recorded, transcribed verbatim and coded and analysed phenomenologically using a QSR-N*Vivo software program. We detected four psychological processes associated with cosmetic breast augmentation surgery (create, improve, repair and restore). The data could further be categorised into one basic drive (femininity), six generating factors (appearance dissatisfaction, ideal figure, self-esteem, comments, clothes and sexuality) and five eliciting factors motivating the decision (media, knowledge of former patients, physicians, finances and romantic partner). These new insights into how and why women seek cosmetic breast augmentation may aid plastic surgeons in enhancing their communication with patients. This can be achieved by addressing the patient's psychological process and motives, and thereby better assist them in making the best decision possible in their particular situation. It may also lay the groundwork for future quantitative studies on the prevalence of certain motives for undergoing such surgery and, as such, help explain the increasing popularity of cosmetic breast-augmentation surgery. Copyright 2009 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

A20 promotes metastasis of aggressive basal-like breast cancers through multi-monoubiquitylation of Snail1.

PubMed

Lee, Ji-Hyung; Jung, Su Myung; Yang, Kyung-Min; Bae, Eunjin; Ahn, Sung Gwe; Park, Jin Seok; Seo, Dongyeob; Kim, Minbeom; Ha, Jihoon; Lee, Jaewon; Kim, Jun-Hyeong; Kim, Jun Hwan; Ooshima, Akira; Park, Jinah; Shin, Donghyuk; Lee, Youn Sook; Lee, Sangho; van Loo, Geert; Jeong, Joon; Kim, Seong-Jin; Park, Seok Hee

2017-10-01

Although the ubiquitin-editing enzyme A20 is a key player in inflammation and autoimmunity, its role in cancer metastasis remains unknown. Here we show that A20 monoubiquitylates Snail1 at three lysine residues and thereby promotes metastasis of aggressive basal-like breast cancers. A20 is significantly upregulated in human basal-like breast cancers and its expression level is inversely correlated with metastasis-free patient survival. A20 facilitates TGF-β1-induced epithelial-mesenchymal transition (EMT) of breast cancer cells through multi-monoubiquitylation of Snail1. Monoubiquitylated Snail1 has reduced affinity for glycogen synthase kinase 3β (GSK3β), and is thus stabilized in the nucleus through decreased phosphorylation. Knockdown of A20 or overexpression of Snail1 with mutation of the monoubiquitylated lysine residues into arginine abolishes lung metastasis in mouse xenograft and orthotopic breast cancer models, indicating that A20 and monoubiquitylated Snail1 are required for metastasis. Our findings uncover an essential role of the A20-Snail1 axis in TGF-β1-induced EMT and metastasis of basal-like breast cancers.

Cancer associated fibroblasts promote tumor growth and metastasis by modulating the tumor immune microenvironment in a 4T1 murine breast cancer model.

PubMed

Liao, Debbie; Luo, Yunping; Markowitz, Dorothy; Xiang, Rong; Reisfeld, Ralph A

2009-11-23

Local inflammation associated with solid tumors commonly results from factors released by tumor cells and the tumor stroma, and promotes tumor progression. Cancer associated fibroblasts comprise a majority of the cells found in tumor stroma and are appealing targets for cancer therapy. Here, our aim was to determine the efficacy of targeting cancer associated fibroblasts for the treatment of metastatic breast cancer. We demonstrate that cancer associated fibroblasts are key modulators of immune polarization in the tumor microenvironment of a 4T1 murine model of metastatic breast cancer. Elimination of cancer associated fibroblasts in vivo by a DNA vaccine targeted to fibroblast activation protein results in a shift of the immune microenvironment from a Th2 to Th1 polarization. This shift is characterized by increased protein expression of IL-2 and IL-7, suppressed recruitment of tumor-associated macrophages, myeloid derived suppressor cells, T regulatory cells, and decreased tumor angiogenesis and lymphangiogenesis. Additionally, the vaccine improved anti-metastatic effects of doxorubicin chemotherapy and enhanced suppression of IL-6 and IL-4 protein expression while increasing recruitment of dendritic cells and CD8(+) T cells. Treatment with the combination therapy also reduced tumor-associated Vegf, Pdgfc, and GM-CSF mRNA and protein expression. Our findings demonstrate that cancer associated fibroblasts promote tumor growth and metastasis through their role as key modulators of immune polarization in the tumor microenvironment and are valid targets for therapy of metastatic breast cancer.

Impaired PRC2 activity promotes transcriptional instability and favors breast tumorigenesis

PubMed Central

Wassef, Michel; Rodilla, Veronica; Teissandier, Aurélie; Zeitouni, Bruno; Gruel, Nadege; Sadacca, Benjamin; Irondelle, Marie; Charruel, Margaux; Ducos, Bertrand; Michaud, Audrey; Caron, Matthieu; Marangoni, Elisabetta; Chavrier, Philippe; Le Tourneau, Christophe; Kamal, Maud; Pasmant, Eric; Vidaud, Michel; Servant, Nicolas; Reyal, Fabien; Meseure, Dider; Vincent-Salomon, Anne; Fre, Silvia; Margueron, Raphaël

2015-01-01

Alterations of chromatin modifiers are frequent in cancer, but their functional consequences often remain unclear. Focusing on the Polycomb protein EZH2 that deposits the H3K27me3 (trimethylation of Lys27 of histone H3) mark, we showed that its high expression in solid tumors is a consequence, not a cause, of tumorigenesis. In mouse and human models, EZH2 is dispensable for prostate cancer development and restrains breast tumorigenesis. High EZH2 expression in tumors results from a tight coupling to proliferation to ensure H3K27me3 homeostasis. However, this process malfunctions in breast cancer. Low EZH2 expression relative to proliferation and mutations in Polycomb genes actually indicate poor prognosis and occur in metastases. We show that while altered EZH2 activity consistently modulates a subset of its target genes, it promotes a wider transcriptional instability. Importantly, transcriptional changes that are consequences of EZH2 loss are predominantly irreversible. Our study provides an unexpected understanding of EZH2's contribution to solid tumors with important therapeutic implications. PMID:26637281

Insulin-Like Growth Factor and Epidermal Growth Factor Signaling in Breast Cancer Cell Growth: Focus on Endocrine Resistant Disease

PubMed Central

Berdiaki, Aikaterini; Tzardi, Maria

2015-01-01

Breast cancer is the most common type of cancer for women worldwide with a lifetime risk amounting to a staggering total of 10%. It is well established that the endogenous synthesis of insulin-like growth factor (IGF) and epidermal growth factor (EGF) polypeptide growth factors are closely correlated to malignant transformation and all the steps of the breast cancer metastatic cascade. Numerous studies have demonstrated that both estrogens and growth factors stimulate the proliferation of steroid-dependent tumor cells, and that the interaction between these signaling pathways occurs at several levels. Importantly, the majority of breast cancer cases are estrogen receptor- (ER-) positive which have a more favorable prognosis and pattern of recurrence with endocrine therapy being the backbone of treatment. Unfortunately, the majority of patients progress to endocrine therapy resistant disease (acquired resistance) whereas a proportion of patients may fail to respond to initial therapy (de novo resistance). The IGF-I and EGF downstream signaling pathways are closely involved in the process of progression to therapy resistant disease. Modifications in the bioavailability of these growth factors contribute critically to disease progression. In the present review therefore, we will discuss in depth how IGF and EGF signaling participate in breast cancer pathogenesis and progression to endocrine resistant disease. PMID:26258011

PRRX2 as a novel TGF-β-induced factor enhances invasion and migration in mammary epithelial cell and correlates with poor prognosis in breast cancer.

PubMed

Juang, Yu-Lin; Jeng, Yung-Ming; Chen, Chi-Long; Lien, Huang-Chun

2016-12-01

TGF-β and cancer progression share a multifaceted relationship. Despite the knowledge of TGF-β biology in the development of cancer, several factors that mediate the cancer-promoting role of TGF-β continue to be identified. This study aimed to identify and characterise novel factors potentially related to TGF-β-mediated tumour aggression in breast cells. We treated the human mammary epithelial cell line MCF10A with TGF-β and identified TGF-β-dependent upregulation of PRRX2, the gene encoding paired-related homeobox 2 transcription factor. Overexpression of PRRX2 enhanced migration, invasion and anchorage-independent growth of MCF10A cells and induced partial epithelial mesenchymal transition (EMT), as determined by partial fibroblastoid morphology of cells, upregulation of EMT markers and partially disrupted acinar structure in a three-dimensional culture. We further identified PLAT, the gene encoding tissue-type plasminogen activator (tPA), as the highest differentially expressed gene in PRRX2-overexpressing MCF10A cells, and demonstrated direct binding and transactivation of the PLAT promoter by PRRX2. Furthermore, PLAT knockdown inhibited PRRX2-mediated enhanced migration and invasion, suggesting that tPA may mediate PRRX2-induced migration and invasion. Finally, the significant correlation of PRRX2 expression with poor survival in 118 primary breast tumour samples (P = 0.027) and the increased PRRX2 expression in metaplastic breast carcinoma samples, which is pathogenetically related to EMT, validated the biological importance of PRRX2-enhanced migration and invasion and PRRX2-induced EMT. Thus, our data suggest that upregulation of PRRX2 may be a mechanism contributing to TGF-β-induced invasion and EMT in breast cancer. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Inflammatory peroxidases promote breast cancer progression in mice via regulation of the tumour microenvironment.

PubMed

Panagopoulos, Vasilios; Leach, Damien A; Zinonos, Irene; Ponomarev, Vladimir; Licari, Giovanni; Liapis, Vasilios; Ingman, Wendy V; Anderson, Peter; DeNichilo, Mark O; Evdokiou, Andreas

2017-04-01

Myeloperoxidase (MPO) and eosinophil peroxidase (EPO) are heme-containing enzymes, well known for their antimicrobial activity, are released in high quantities by infiltrating immune cells in breast cancer. However, the functional importance of their presence within the tumour microenvironment is unclear. We have recently described a new role for peroxidases as key regulators of fibroblast and endothelial cell functionality. In the present study, we investigate for the first time, the ability of peroxidases to promote breast cancer development and progression. Using the 4T1 syngeneic murine orthotopic breast cancer model, we examined whether increased levels of peroxidases in developing mammary tumours influences primary tumour growth and metastasis. We showed that MPO and EPO stimulation increased mammary tumour growth and enhanced lung metastases, effects that were associated with reduced tumour necrosis, increased collagen deposition and neo-vascularisation within the primary tumour. In vitro, peroxidase treatment, robustly stimulated human mammary fibroblast migration and collagen type I and type VI secretion. Mechanistically, peroxidases induced the transcription of pro-tumorigenic and metastatic MMP1, MMP3 and COX-2 genes. Taken together, these findings identify peroxidases as key contributors to cancer progression by augmenting pro-tumorigenic collagen production and angiogenesis. Importantly, this identifies inflammatory peroxidases as therapeutic targets in breast cancer therapy.

Prolonged survival after diagnosis of brain metastasis from breast cancer: contributing factors and treatment implications.

PubMed

Honda, Yayoi; Aruga, Tomoyuki; Yamashita, Toshinari; Miyamoto, Hiromi; Horiguchi, Kazumi; Kitagawa, Dai; Idera, Nami; Goto, Risa; Kuroi, Katsumasa

2015-08-01

The prognosis of breast cancer-derived brain metastasis is poor, but new drugs and recent therapeutic strategies have helped extend survival in patients. Prediction of therapeutic responses and outcomes is not yet possible, however. In a retrospective study, we examined prognostic factors in patients with breast cancer-derived brain metastasis, and we tested the prognostic utility of a breast cancer-specific Graded Prognostic Assessment in these patients. Sixty-three patients diagnosed with brain metastasis from breast cancer treated surgically and adjuvantly were included. We examined clinical variables per primary tumor subtype: ER+/HER2- (luminal), HER2+ (human epidermal growth factor receptor type 2-enriched) or ER-/PR-/HER2- (triple negative). We also categorized patients' breast cancer-specific Graded Prognostic Assessment scores and analyzed post-brain metastasis survival time in relation to these categories. The breast cancers comprised the following subtypes: luminal, n = 18; human epidermal growth factor receptor type 2-enriched, n = 27 and triple-negative, n = 18; median survival per subtype was 11, 37 and 3 months, respectively. Survival of human epidermal growth factor receptor type 2-enriched patients was longer, though not significantly (P = 0.188), than that of luminal patients. Survival of triple-negative patients was significantly short (vs. human epidermal growth factor receptor type 2-enriched patients, P < 0.001). Karnofsky performance status, HER2 status and the disease-free interval (from initial treatment to first recurrence) were shown to be significant prognostic factors (Karnofsky performance status < 70: relative risk 2.08, P = 0.028; HER2+: relative risk 2.911, P = 0.004; disease-free interval < 24 months: relative risk 1.933, P = 0.011). Breast cancer-specific Graded Prognostic Assessment scores reflected disease-free intervals and survival times. Our data indicate that breast cancer-specific Graded Prognostic Assessment

[Prognostic factors of early breast cancer].

PubMed

Almagro, Elena; González, Cynthia S; Espinosa, Enrique

2016-02-19

Decision about the administration of adjuvant therapy for early breast cancer depends on the evaluation of prognostic factors. Lymph node status, tumor size and grade of differentiation are classical variables in this regard, and can be complemented by hormonal receptor status and HER2 expression. These factors can be combined into prognostic indexes to better estimate the risk of relapse or death. Other factors are less important. Gene profiles have emerged in recent years to identify low-risk patients who can forgo adjuvant chemotherapy. A number of profiles are available and can be used in selected cases. In the future, gene profiling will be used to select patients for treatment with new targeted therapies. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

Progress in promoting breast-feeding, combating malnutrition, and composition and use of infant formula, 1981-2006.

PubMed

Heird, William C

2007-02-01

More than 90% of women in developing countries and 50 to 90% of women in industrialized countries now initiate breast-feeding, a marked improvement from 25 y ago. The duration of breast-feeding has lengthened, but fewer than 35% of infants worldwide are still exclusively breast-fed at 4 mo of age. Considerable progress has also been made in combating infant malnutrition. In 1980, 47% of under-5-y-old children in developing countries were stunted. This percentage declined to 29% in 2005. Major advances in formula use and composition include the introduction of formulas tailored to the perceived needs of low-birth-weight infants and the development of fortifiers to overcome the nutritional deficits of human milk for the preterm infant. More recently, postdischarge formulas were introduced and are now being used widely, often in combination with breast-feeding. Formulas for term infants also have undergone a number of changes in the past 25 y to better reproduce the composition of human milk and/or the response of the breast-fed infant. The use of whey-predominant rather than casein-predominant formulas has increased, as has the use of iron-fortified formulas. Cow's milk is introduced into the infant's diet much later than 25 y ago. Despite the progress that has been made in promoting breast-feeding and in the quality of infant formulas, further improvements in the duration of breast-feeding and in the composition of infant formulas are needed.

Inactivation of FBXW7/hCDC4-β expression by promoter hypermethylation is associated with favorable prognosis in primary breast cancer

PubMed Central

2010-01-01

Introduction Mutational inactivation of the FBXW7/hCDC4 tumor suppressor gene (TSG) is common in many cancer types, but infrequent in breast cancers. This study investigates the presence and impact of FBXW7/hCDC4 promoter methylation in breast cancer. Methods FBXW7/hCDC4-β expression and promoter methylation was assessed in 161 tumors from two independent breast cancer cohorts. Associations between methylation status and clinicopathologic characteristics were assessed by Fisher's exact test. Survival was analyzed using the Kaplan-Meier method in addition to modeling the risk by use of a multivariate proportional hazard (Cox) model adjusting for possible confounders of survival. Results Methylation of the promoter and loss of mRNA expression was found both in cell lines and primary tumors (43% and 51%, respectively). Using Cox modeling, a trend was found towards decreased hazard ratio (HR) for death in women with methylation of FBXW7/hCDC4-β in both cohorts (HR 0.53 (95% CI 0.23 to 1.23) and HR 0.50 (95% CI 0.23 to 1.08), respectively), despite an association between methylation and high-grade tumors (P = 0.017). Interestingly, in subgroups of patients whose tumors are p53 mutated or lymph-node positive, promoter methylation identified patients with significantly improved survival (P = 0.048 and P = 0.017, respectively). Conclusions We demonstrate an alternative mechanism for inactivation of the TSG FBXW7/hCDC4, namely promoter specific methylation. Importantly, in breast cancer, methylation of FBXW7/hCDC4-β is related to favorable prognosis despite its association with poorly differentiated tumors. Future work may define whether FBXW7/hCDC4 methylation is a biomarker of the response to chemotherapy and a target for epigenetic modulation therapy. PMID:21122106

The AA genotype of the regulatory BCL2 promoter polymorphism ( 938C>A) is associated with a favorable outcome in lymph node negative invasive breast cancer patients.

PubMed

Bachmann, Hagen S; Otterbach, Friedrich; Callies, Rainer; Nückel, Holger; Bau, Maja; Schmid, Kurt W; Siffert, Winfried; Kimmig, Rainer

2007-10-01

Expression of the antiapoptotic and antiproliferative protein Bcl-2 has been repeatedly shown to be associated with better clinical outcome in breast cancer. We recently showed a novel regulatory (-938C>A) single-nucleotide polymorphism (SNP) in the inhibitory P2 BCL2 gene promoter generating significantly different BCL2 promoter activities. Paraffin-embedded neoplastic and nonneoplastic tissues from 274 patients (161 still alive after a follow-up period of at least 80 months) with primary unilateral invasive breast carcinoma were investigated. Bcl-2 expression of tumor cells was shown by immunohistochemistry; nonneoplastic tissues were used for genotyping. Both the Bcl-2 expression and the (-938C>A) genotypes were correlated with the patients' survival. Kaplan-Meier curves revealed a significant association of the AA genotype with increased survival (P = 0.030) in lymph node-negative breast cancer patients, whereas no genotype effect could be observed in lymph node-positive cases. Ten-year survival rates were 88.6% for the AA genotype, 78.4% for the AC genotype, and 65.8% for the CC genotype. Multivariable Cox regression identified the BCL2 (-938CC) genotype as an independent prognostic factor for cancer-related death in lymph node-negative breast carcinoma patients (hazard ratio, 3.59; P = 0.032). Immunohistochemical Bcl-2 expression was significantly associated with the clinical outcome of lymph node-positive but not of lymph node-negative breast cancer patients. In lymph node-negative cases, the (-938C>A) SNP was both significantly related with the immunohistochemically determined level of Bcl-2 expression (P = 0.044) and the survival of patients with Bcl-2-expressing carcinomas (P = 0.006). These results suggest the (-938C>A) polymorphism as a survival prognosticator as well as indicator of a high-risk group within patients with lymph node-negative breast cancer.

Breast milk-derived exosomes promote intestinal epithelial cell growth.

PubMed

Hock, Alison; Miyake, Hiromu; Li, Bo; Lee, Carol; Ermini, Leonardo; Koike, Yuhki; Chen, Yong; Määttänen, Pekka; Zani, Augusto; Pierro, Agostino

2017-05-01

Breast milk administration prevents necrotizing enterocolitis (NEC). However, the mechanism remains unclear. Exosomes are cell-derived vesicles highly present in human milk and regulate intercellular signaling, inflammation, and immune response. We hypothesized that milk-derived exosomes beneficially affect intestinal epithelial cells. Rat milk was collected, and exosomes were isolated using ExoQuick reagent and visualized by Nanoparticle Tracking Analysis. Protein was extracted from encapsulating exosomes, and concentration was measured. 2×10 4 intestinal epithelial cells (IEC-18) were treated for five hours with 0.5-μg/μl exosomes, an equal volume of exosome-free milk, or control solution (PBS). IEC-18 viability was measured using a colorimetric assay (MTT), and gene expression was analyzed by qRT-PCR. Data were compared using one-way ANOVA with Bonferroni post-test. Rat milk was collected, and exosome isolation was confirmed. Compared to control, treatment with exosomes significantly increased IEC viability, proliferation, and stem cell activity (all p<0.05). However, administration of exosome-free milk had less significant effects. Rat milk-derived exosomes promote IEC viability, enhance proliferation, and stimulate intestinal stem cell activity. These findings provide insight into the mechanism of action of breast milk in the intestines. Exosome administration is a promising prevention method for infants at risk of developing NEC when breastfeeding is not tolerated. Copyright © 2017 Elsevier Inc. All rights reserved.

Factors influencing breast feeding.

PubMed Central

McKean, K S; Baum, J D; Sloper, K

1975-01-01

A survey is reported of infant feeding practice at the time of discharge from a single maternity ward. It is shown that a change in the attitude of nursing staff increased the number of mothers breast feeding their infants and eliminated the practice of giving the infants formula feed complements. This change in attitude, however, did nothing to prevent the rapid decline in lactation after leaving hospital, such that 50% of mothers discharged breast feeding were no longer doing so by 2 months. The early introduction of solid feeds was common practice, 50% of mothers discharged breast feeding having introduced mixed feeds within 2 months. Successful lactation was found to be commoner in those mothers who had themselves been breast fed in infancy and in mothers from socioeconomic classes I and II. Successful lactation was not related to parity. The survey also shows the influential role of the health visitor, district nurse, and midwife upon mothers' decisions about infant feeding. PMID:1170810

[Night shift work and prolactin as a breast cancer risk factor].

PubMed

Bukowska, Agnieszka; Pepłońska, Beata

2013-01-01

Prolactin - a hormone secreted in a circadian rhythm acts as a regulator of growth and development of the mammary glands. It has been observed that working at night increases breast cancer risk in women. Night shift work, probably carcinogenic to humans (Group 2A IARC), can disrupt a circadian rhythm, and thus potentially alter the rhythm of prolactin secretion. The aim of our work was to review epidemiological evidence on the association between prolactin and the risk of breast cancer and the influence of work at night on prolactin secretion. Search was done in the Medline database by keywords (shift work, work at night, risk of breast cancer and prolactin). 'The increased proliferation of breast cells activated by prolactin can promote the development of cancer. The results of the largest epidemiological prospective studies suggest the association between prolactin levels and the risk of breast cancer in women. So far, only seven studies have investigated the association between work at night and prolactin secretion. In three studies lower concentrations of prolactin have been observed in night shift workers. No relationship between the night shift work duration and prolactin level in women have been reported. Night shift work can modify the profile of prolactin secretion in night workers, probably decreasing the secretion of this hormone at night. It is therefore unlikely that prolactin plays an important role in the development of breast cancer in women working at night. This conclusion is based on the results of a few epidemiological studies.

Treatment for liver metastases from breast cancer: Results and prognostic factors

PubMed Central

Li, Xiao-Ping; Meng, Zhi-Qiang; Guo, Wei-Jian; Li, Jie

2005-01-01

AIM: Liver metastases from breast cancer (BCLM) are associated with poor prognosis. Cytotoxic chemotherapy can result in regression of tumor lesions and a decrease in symptoms. Available data, in the literature, also suggest a subgroup of patients may benefit from surgery, but few talked about transcatheter arterial chemoembolization (TACE). We report the results of TACE and systemic chemotherapy for patients with liver metastases from breast cancer and evaluate the prognostic factors. METHODS: Forty-eight patients with liver metastases, from proved breast primary cancer were treated with TACE or systemic chemotherapy between January 1995 and December 2000. Treatment results were assessed according to WHO criteria, along with analysis of prognostic factors for survival using Cox regression model. RESULTS: The median follow-up was 28 mo (1-72 mo). Response rates were calculated for the TACE group and chemotherapy group, being 35.7% and 7.1%, respectively. The difference was significant. The one-, two- and three-year Survival rates for the TACE group were 63.04%, 30.35%, and 13.01%, and those for the systemic chemotherapy group were 33.88%, 11.29%, and 0%. According to univariate analysis, variables significantly associated with survival were the lymph node status of the primary cancer, the clinical stage of liver metastases, the Child-Pugh grade, loss of weight. Other factors such as age, the intervals between the primary to the metastases, the maximal diameter of the liver metastases, the number of liver metastases, extrahepatic metastasis showed no prognostic significances. These factors mentioned above such as the lymph node status of the primary cancer, the clinical stage of liver metastases, the Child-Pugh grade, loss of weight were also independent factors in multivariate analysis. CONCLUSION: TACE treatment of liver metastases from breast cancer may prolong survival in certain patients. This approach offers new promise for the curative treatment of the

Tracing anti-cancer and cancer-promoting actions of all-trans retinoic acid in breast cancer to a RARα epigenetic mechanism of mammary epithelial cell fate.

PubMed

Rossetti, Stefano; Ren, MingQiang; Visconti, Nicolo; Corlazzoli, Francesca; Gagliostro, Vincenzo; Somenzi, Giulia; Yao, Jin; Sun, Yijun; Sacchi, Nicoletta

2016-12-27

A hallmark of cancer cells is the ability to evade the growth inhibitory/pro-apoptotic action of physiological all-trans retinoic acid (RA) signal, the bioactive derivative of Vitamin A. However, as we and others reported, RA can also promote cancer cell growth and invasion. Here we show that anticancer and cancer-promoting RA actions in breast cancer have roots in a mechanism of mammary epithelial cell morphogenesis that involves both transcriptional (epigenetic) and non-transcriptional RARα (RARA) functions. We found that the mammary epithelial cell-context specific degree of functionality of the RARA transcriptional (epigenetic) component of this mechanism, by tuning the effects of the non-transcriptional RARA component, determines different cell fate decisions during mammary morphogenesis. Indeed, factors that hamper the RARA epigenetic function make physiological RA drive aberrant morphogenesis via non-transcriptional RARA, thus leading to cell transformation. Remarkably, also the cell context-specific degree of functionality of the RARA epigenetic component retained by breast cancer cells is critical to determine cell fate decisions in response to physiological as well as supraphysiological RA variation. Overall this study supports the proof of principle that the epigenetic functional plasticity of the mammary epithelial cell RARA mechanism, which is essential for normal morphogenetic processes, is necessary to deter breast cancer onset/progression consequent to the insidious action of physiological RA.

A probable risk factor of female breast cancer: study on benign and malignant breast tissue samples.

PubMed

Rehman, Sohaila; Husnain, Syed M

2014-01-01

The study reports enhanced Fe, Cu, and Zn contents in breast tissues, a probable risk factor of breast cancer in females. Forty-one formalin-fixed breast tissues were analyzed using atomic absorption spectrophotometry. Twenty malignant, six adjacent to malignant and 15 benign tissues samples were investigated. The malignant tissues samples were of grade 11 and type invasive ductal carcinoma. The quantitative comparison between the elemental levels measured in the two types of specimen (benign and malignant) tissues (removed after surgery) suggests significant elevation of these metals (Fe, Cu, and Zn) in the malignant tissue. The specimens were collected just after mastectomy of women aged 19 to 59 years from the hospitals of Islamabad and Rawalpindi, Pakistan. Most of the patients belong to urban areas of Pakistan. Findings of study depict that these elements have a promising role in the initiation and development of carcinoma as consistent pattern of elevation for Fe, Cu, and Zn was observed. The results showed the excessive accumulation of Fe (229 ± 121 mg/L) in malignant breast tissue samples of patients (p < 0.05) to that in benign tissues samples (49.1 ± 11.4 mg/L). Findings indicated that excess accumulation of iron in malignant tissues can be a risk factor of breast cancer. In order to validate our method of analysis, certified reference material muscle tissue lyophilized (IAEA) MA-M-2/TM was analyzed for metal studied. Determined concentrations were quite in good agreement with certified levels. Asymmetric concentration distribution for Fe, Cu, and Zn was observed in both malignant and benign tissue samples.

Reproductive history and breast cancer risk.

PubMed

Kobayashi, Shunzo; Sugiura, Hiroshi; Ando, Yoshiaki; Shiraki, Norio; Yanagi, Takeshi; Yamashita, Hiroko; Toyama, Tatsuya

2012-10-01

The fact that reproductive factors have significant influence on the risk of breast cancer is well known. Early age of first full-term birth is highly protective against late-onset breast cancers, but each pregnancy, including the first one, increases the risk of early-onset breast cancer. Estradiol and progesterone induce receptor activator of NF-kappa B ligand (RANKL) in estrogen receptor (ER)- and progesterone receptor (PgR)-positive luminal cells. RANKL then acts in a paracrine fashion on the membranous RANK of ER/PgR-negative epithelial stem cells of the breast. This reaction cascade is triggered by chorionic gonadotropin during the first trimester of pregnancy and results in the morphological and functional development of breast tissue. On the other hand, the administration of non-steroidal anti-inflammatory drugs in the early steps of weaning protects against tumor growth through reduction of the acute inflammatory reaction of post lactation remodeling of breast tissue. This is experimental evidence that may explain the short-term tumor-promoting effect of pregnancy. The protective effect of prolonged breast feeding may also be explained, at least in a part, by a reduced inflammatory reaction due to gradual weaning. Delay of first birth together with low parity and short duration of breast feeding are increasing social trends in developed countries. Therefore, breast cancer risk as a result of reproductive factors will not decrease in these countries in the foreseeable future. In this review, the significance of reproductive history with regard to the risk of breast cancers will be discussed, focusing on the age of first full-term birth and post lactation involution of the breast.

Epidermal growth factor promotes a mesenchymal over an amoeboid motility of MDA-MB-231 cells embedded within a 3D collagen matrix

NASA Astrophysics Data System (ADS)

Geum, Dongil T.; Kim, Beum Jun; Chang, Audrey E.; Hall, Matthew S.; Wu, Mingming

2016-01-01

The receptor of epidermal growth factor (EGFR) critically regulates tumor cell invasion and is a potent therapeutic target for treatment of many types of cancers, including carcinomas and glioblastomas. It is known that EGF regulates cell motility when tumor cells are embedded within a 3D biomatrix. However, roles of EGF in modulating tumor cell motility phenotype are largely unknown. In this article, we report that EGF promotes a mesenchymal over an amoeboid motility phenotype using a malignant breast tumor cell line, MDA-MB-231, embedded within a 3D collagen matrix. Amoeboid cells are rounded in shape, while mesenchymal cells are elongated, and their migrations are governed by a distinctly different set of biomolecules. Using single cell tracking analysis, we also show that EGF promotes cell dissemination through a significant increase in cell persistence along with a moderate increase of speed. The increase of persistence is correlated with the increase of the percentage of the mesenchymal cells within the population. Our work reveals a novel role of microenvironmental cue, EGF, in modulating heterogeneity and plasticity of tumor cell motility phenotype. In addition, it suggests a potential visual cue for diagnosing invasive states of breast cancer cells. This work can be easily extended beyond breast cancer cells.

Using Clinical Factors and Mammographic Breast Density to Estimate Breast Cancer Risk: Development and Validation of a New Predictive Model

PubMed Central

Tice, Jeffrey A.; Cummings, Steven R.; Smith-Bindman, Rebecca; Ichikawa, Laura; Barlow, William E.; Kerlikowske, Karla

2009-01-01

Background Current models for assessing breast cancer risk are complex and do not include breast density, a strong risk factor for breast cancer that is routinely reported with mammography. Objective To develop and validate an easy-to-use breast cancer risk prediction model that includes breast density. Design Empirical model based on Surveillance, Epidemiology, and End Results incidence, and relative hazards from a prospective cohort. Setting Screening mammography sites participating in the Breast Cancer Surveillance Consortium. Patients 1 095 484 women undergoing mammography who had no previous diagnosis of breast cancer. Measurements Self-reported age, race or ethnicity, family history of breast cancer, and history of breast biopsy. Community radiologists rated breast density by using 4 Breast Imaging Reporting and Data System categories. Results During 5.3 years of follow-up, invasive breast cancer was diagnosed in 14 766 women. The breast density model was well calibrated overall (expected–observed ratio, 1.03 [95% CI, 0.99 to 1.06]) and in racial and ethnic subgroups. It had modest discriminatory accuracy (concordance index, 0.66 [CI, 0.65 to 0.67]). Women with low-density mammograms had 5-year risks less than 1.67% unless they had a family history of breast cancer and were older than age 65 years. Limitation The model has only modest ability to discriminate between women who will develop breast cancer and those who will not. Conclusion A breast cancer prediction model that incorporates routinely reported measures of breast density can estimate 5-year risk for invasive breast cancer. Its accuracy needs to be further evaluated in independent populations before it can be recommended for clinical use. PMID:18316752

Cultural sensitivity and health promotion: assessing breast cancer education pamphlets designed for African American women.

PubMed

Kline, Kimberly N

2007-01-01

This study discusses the implications for cultural sensitivity of the rhetorical choices in breast cancer education materials developed specifically for African American audiences by national organizations. Using the PEN-3 model of cultural sensitivity as an analytic framework for a generative rhetorical criticism, this study revealed that adaptations have been made in some pamphlets to acknowledge African American cultural values related to community, self-reliance, spirituality, and distrust of the Western medical establishment, but many messages could be revised to achieve a more comprehensive, balanced, accurate, and audience-specific discussion of the breast cancer issue. Achieving cultural sensitivity in health promotion materials necessitates attention to nuanced meanings in messages, revision of questionable arguments and evidence, and avoidance of ambiguity.

Factors associated with return to work of breast cancer survivors: a systematic review

PubMed Central

2014-01-01

Background The breast cancer survival rate is the highest among all types of cancers, and survivors returning to work after completing treatment is extremely important in regards to economy and rehabilitation. The aim of this systematic review study is to identify the prevalence of breast cancer survivors who return to work (RTW) and the factors associated to RTW. Methods A computer based literature search was carried out. "PubMed, Cochrane Library, Embase, Web of Science, and Science Direct" databases were searched systematically. Our search strategy identified a total of 12,116 papers of which 26 studies met the inclusion criteria and quality assessment. These were original papers published between January 2003 and January 2013. Results The trends in RTW differ among countries for the breast cancer survivors. The time to RTW after successful cancer treatment also varies among the countries and by ethnicity. The prevalence of the RTW varies from 43% to 93% within one year of diagnosis. The prevalence of the RTW for the Netherland is the lowest in the world (43%). The United States survivors showed the highest RTW (93%) within 12 months of the diagnosis. Numerous barriers and facilitators were identified as factors that affect RTW. For instance, socio-demographic factors such as education and ethnicity; treatment oriented factors such as chemotherapy; work related factors such as heavy physical work; disease related factors such as poor health condition and fatigue; and psychological factors such as depression and emotional distress, act as barriers of RTW. In contrast, social, family, employer support, and financial independency emerge as key facilitators in enabling breast cancer survivors to return and continue work. Conclusion Minimising these identified barriers and strengthening these facilitators could further improve the work condition and increase the percentage of RTW among the breast cancer survivors. PMID:25437351

Promoting breast health among women in the U.S. Virgin Islands: a focused study of the needs of Caribbean women.

PubMed

Underwood, Sandra; Johnson, Edith Ramsay; Callwood, Gloria; Evans, Edris E; Matthew, Alina; Scotland-Brooks, Casandra; Hanley, Chantal; Johnson-Harrigan, Damali; LeFlore, Devette; Williams, Dionne; Samuels, Harricia; Francis, Jahtara; Arthur, Jamela; Clinkscales, Jowana; Joseph, Martha; Heskey, Nihjole; D'Abreau, Rachel; Fleming, Rashima; Penn, Stacey; Browne, Tameka A; Donastorg, Tiffany; Scarbriel, Yvette

2007-12-01

Breast cancer is the number one cause of cancer death among women in the United States Virgin Islands. Consequently, the Bureau of Health has identified breast cancer as a priority health concern. Within the medical community, increasing emphasis is being placed on the importance of hereditary, familial, environmental, and behavioral risk factors to breast cancer control. Little research has been conducted regarding these factors, however, to explore their influence on breast cancer detection and breast cancer risk management. This report highlights the outcomes of a study undertaken to explore the associations between breast cancer risk, risk assessment, risk communication, screening, and receptivity to the management of breast cancer risk among women from the United States Virgin Islands. Results of this study suggest a need within the territory to expand the systems that are responsible for monitoring and reporting breast cancer trends; forums to discuss concerns of women relative to breast health; forums to discuss communication with health-care providers; and, research efforts that address breast cancer detection and control among women in the United States Virgin Islands.

Promoting Breast Health among Women in the U.S. Virgin Islands: A Focused Study of the Needs of Caribbean Women

PubMed Central

Underwood, Sandra Millon; Ramsay-Johnson, Edith M.; Callwood, Gloria; Evans, Edris E.; Matthew, Alina; Scotland-Brooks, Casandra; Hanley, Chantal; Johnson-Harrigan, Damali; LeFlore, Devette; Williams, Dionne; Samuels, Harricia; Francis, Jahtara; Arthur, Jamela; Clinkscales, Jowana; Joseph, Martha; Heskey, Nihjole; D’Abreau, Rachel; Fleming, Rashima; Penn, Stacey; Browne, Tameka A.; Donastorg, Tiffany; Scarbriel, Yvette

2011-01-01

Breast cancer is the number one cause of cancer death among women in the United States Virgin Islands. Consequently, the Bureau of Health has identified breast cancer as a priority health concern. Within the medical community, increasing emphasis is being placed on the importance of hereditary, familial, environmental, and behavioral risk factors to breast cancer control. Little research has been conducted regarding these factors, however, to explore their influence on breast cancer detection and breast cancer risk management. This report highlights the outcomes of a study undertaken to explore the associations between breast cancer risk, risk assessment, risk communication, screening, and receptivity to the management of breast cancer risk among women from the United States Virgin Islands. Results of this study suggest a need within the territory to expand the systems that are responsible for monitoring and reporting breast cancer trends; forums to discuss concerns of women relative to breast health; forums to discuss communication with health-care providers; and, research efforts that address breast cancer detection and control among women in the United States Virgin Islands. PMID:18318332

Bilateral breast keloids in an elderly woman associated with bilateral breast cancers and high concentration of serum tumor growth factor-β.

PubMed

Sakaguchi, Masanobu; Fukumoto, Takeshi; Fujishima, Fumiyoshi; Fukuda, Kaori; Kozaru, Takeshi; Ban, Masao; Oka, Masahiro

2017-11-01

We report a case of bilateral annular breast keloids in a 72-year-old woman who had been suffering from bilateral breast cancers. Histopathologically, the keloids showed unique distribution of α-SMA+, CD34- myofibroblasts and α-SMA-, CD34+ fibroblasts depending on the region. High serum levels of tumor growth factor-β were detected at 6 months after the development of the breast keloids, but not at 10 months. CD163-positive cells were abundantly detected in the skin of the elevated portion of the keloids. In contrast, these cells were considerably less numerous in the skin of the central healing portion compared with the skin of the elevated expanding portion. One interesting idea based on these results is that high levels of tumor growth factor-β released from CD163-positive cells played a crucial role in the formation of breast keloids through active induction of fibroblast differentiation into myofibroblasts. The present case strongly supports the previously proposed idea that keloids can form as a paraneoplastic phenomenon in breast cancer patients with keloid constitution. © 2017 Japanese Dermatological Association.

Knowledge and Perceptions of Common Breast Cancer Risk Factors in Northern Saudi Arabia

PubMed Central

Alrashidi, Ali Ghannam; Ahmed, Hussain Gadelkarim; Alshammeri, Kalaf Jaze Kalaf; Alrashedi, Sami Awejan; ALmutlaq, Bassam Ahmed; Alshammari, Fayez Nashi Motlaq; Alshudayyid, Abdulaziz Abdulrahman Hamad; Alshammari, Abdulrahman Ayed Jazza; Anazi, Fahad Mohammed Samran; Alshammari, Wasmiah Marzouq; Alshammari, Hamdan Sulaiman Ayed; Alshammari, Eid Fahad Habeeb

2017-01-01

Background: Breast cancer is the second leading cause of cancer death in women around the world. The degree of adoption of a preventive lifestyle offers valuable information for planning appropriate intervention programs for improving women’s health. The objective of the present study was to assess the levels of breast cancer related knowledge among a Northern Saudi population. Methodology: In this cross sectional study, data were obtained from 566 Saudi volunteers living in the city of Hail, the Kingdom of Saudi Arabia (KSA). Results: With regard to breast cancer risk factors, 427/566 (75.4%) of participants answered in the affirmative to whether breast cancer could be inherited. For early puberty and late menopause, 209/566 (37%) were in agreement with increased risk, for low and delayed child birth, 261/566 (46%), and for overweight and obesity, 210/566(37%). For the question of whether natural breast feeding can reduce the risk of breast cancer, only 35/566 (6.2%) said yes. Conclusion: There is a general lack of knowledge regarding several BC risk factors among the northern Saudi community which necessitates urgent implementation of educational programs. PMID:29072404

Risk factors, lifetime risk, and age at onset of breast cancer.

PubMed

Fraser, G E; Shavlik, D

1997-08-01

We evaluated the relationship between exposure variables and both lifetime risk and mean age at diagnosis of breast cancer in subjects from the Adventist Health Study who developed breast cancer before the age of 91 years. Multiple decrement life-table analysis was used. This study provided data from 20,341 women followed for 6 years. In the total population, 30-year-old women with a parental history of any cancer or a maternal history of breast cancer had, respectively, 72% (P < 0.002) and 98% (P < 0.03) higher lifetime risks of breast cancer. Thirty-year-old women who had their first delivery after age 24 years or body mass indices above the 50th percentile had, respectively, 53% (P < 0.007) or 57% (P = 0.01) greater lifetime risk of breast cancer. Women who exercised infrequently had a 27% higher life-time risk (P = 0.09) and an age at diagnosis of breast cancer 6.6 years younger (P < 0.005) than other women. Standard risk factors account for substantial increases in lifetime risk of breast cancer and may be associated with differences in age at diagnosis.

Favorable Changes in Serum Estrogens and Other Biological Factors After Weight Loss in Overweight or Obese Breast Cancer Survivors

PubMed Central

Rock, Cheryl L.; Pande, Chetna; Flatt, Shirley W.; Ying, Carl; Pakiz, Bilge; Parker, Barbara A.; Williams, Kathryn; Bardwell, Wayne A.; Heath, Dennis D.; Nichols, Jeanne F.

2014-01-01

Background Obesity is associated with increased risk for recurrence and all-cause mortality in breast cancer survivors. Excess adiposity is associated with increased estrogen, insulin, and leptin, and decreased sex hormone binding globulin (SHBG) concentrations, which may promote breast cancer progression and recurrence. This study aimed to assess the effects of weight loss on these factors. Patients and Methods Overweight or obese breast cancer survivors (N = 220) who were enrolled in a weight loss intervention study provided baseline and follow-up blood samples and weight data. Serum estrogens, SHBG, insulin, and leptin were measured at baseline, 6 and 18 months. Results Weight loss of ≥5% of initial weight decreased leptin and insulin compared with those who did not achieve that amount of weight loss (P < .0001). Weight loss also increased SHBG at 6 and 18 months (P < .01). Postmenopausal women who lost ≥5% of body weight at 6 months had lower estrone (P = .02), estradiol (P = .002), and bioavailable estradiol (P = .001) concentrations than women who did not lose at least 5% of body weight, and weight loss at 18 months was significantly related to change in serum bioavailable estradiol concentration (P = 0.02). Conclusion Favorable changes in estrogens, SHBG, insulin, and leptin were observed in association with weight loss in these overweight or obese women who had been diagnosed and treated for breast cancer. Weight loss appears to have favorable effects on hormonal and biological factors associated with increased risk for recurrence and poorer prognosis. PMID:23375717

Sexual Behavior Pattern and Related Factors in Women with Breast Cancer in Iran.

PubMed

Rashidi, Sanaz; Dashti, Forouzandeh

2015-12-18

Despite the most of treatment team efforts focused on the maintaining patient's life, attention to sexual issues don't be considered. This stud is designed to determine the sexual behavior pattern and related factors in women with breast cancer. This descriptive- correlation study was performed on 90 women that diagnosed with breast Cancer that was admitted to sayed-al- shohada hospital of Isfahan in 2010. Sampling method was available (non- random sampling) and Sexual Behavior Pattern determined with 3 domains: sexual identity, sexual role and sexual function. Data collection tools, was a questionnaire that made by the researcher and was used after determining the validity and reliability. For data analysis, was used of Descriptive- analytic statistics, frequency and ANOVA and Pearson correlation analytical tests in the SPSS statistical software (version 16). Cases had 60% of Desirable sexual identity, 50% of Desirable sexual role, 40% Desirable sexual function and were be able to play 47.61% Desirable sexual behavior. Participants that their husbands had Elementary education had more desirable sexual behavior (p<0.031). Cases that were homemaker had more desirable Sexual behavior than of were working and retired (p<0.023). Non-surgical treatment with chemotherapy, radiotherapy and hormone therapy had a negative impact on sexual behavior (p<0.014). Study of sexual behavior pattern that is one of the important aspects of health, Provide valuable information to nurses and medical team and will be enhance the quality of provided services. Adopt appropriate strategies and interventions to promote sexual health, breast cancer is recommended.

Prolonged breast-feeding is an independent risk factor for postmenopausal osteoporosis.

PubMed

Okyay, Duygu Ozkale; Okyay, Emre; Dogan, Erbil; Kurtulmus, Secil; Acet, Ferruh; Taner, Cuneyt Eftal

2013-03-01

This study investigated the effects of parity and age at first pregnancy and breast-feeding, as well as duration of BF for total and per child on postmenopausal osteoporosis. The study was conducted among 542 cases who were divided based on the presence or absence of osteoporosis. Patients were separated according to their first pregnancy and breast-feeding age as before or after 27 years. Osteoporosis was defined as a T score of -2.5 or lower. Parity, age at first pregnancy and breast-feeding, breast-feeding period for total and average duration per child according to a questionnaire were assessed. Osteoporosis group had significantly lower parity compared to non-osteoporosis group. The age at first pregnancy and breast-feeding<27 age were significantly more frequent in osteoporosis group. They also had prolonged breast-feeding period. Women who had a breast-feeding period per child>1 year under age 27 was higher in osteoporosis group. In multivariate analysis, women who breast-fed>1 year per child had the highest risk for osteoporosis (odds ratio: 12.92; 95% confidence interval, 3.1-52.6) and osteoporosis risk for women who breast-fed>1 year per child under age 27 was 7.1. Increased parity was associated with a significant protective effect for osteoporosis. Extended breast-feeding period per child>1 year is the highest risk factor for osteoporosis independent of first breast-feeding age. However, high parity has a protective effect. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

TNF{alpha} acting on TNFR1 promotes breast cancer growth via p42/P44 MAPK, JNK, Akt and NF-{kappa}B-dependent pathways

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rivas, Martin A.; Carnevale, Romina P.; Proietti, Cecilia J.

2008-02-01

Tumor necrosis factor {alpha} (TNF{alpha}) enhances proliferation of chemically-induced mammary tumors and of T47D human cell line through not fully understood pathways. Here, we explored the intracellular signaling pathways triggered by TNF{alpha}, the participation of TNF{alpha} receptor (TNFR) 1 and TNFR2 and the molecular mechanism leading to breast cancer growth. We demonstrate that TNF{alpha} induced proliferation of C4HD murine mammary tumor cells and of T47D cells through the activation of p42/p44 MAPK, JNK, PI3-K/Akt pathways and nuclear factor-kappaB (NF-{kappa}B) transcriptional activation. A TNF{alpha}-specific mutein selectively binding to TNFR1 induced p42/p44 MAPK, JNK, Akt activation, NF-{kappa}B transcriptional activation and cell proliferation,more » just like wild-type TNF{alpha}, while a mutein selective for TNFR2 induced only p42/p44 MAPK activation. Interestingly, blockage of TNFR1 or TNFR2 with specific antibodies was enough to impair TNF{alpha} signaling and biological effect. Moreover, in vivo TNF{alpha} administration supported C4HD tumor growth. We also demonstrated, for the first time, that injection of a selective inhibitor of NF-{kappa}B activity, Bay 11-7082, resulted in regression of TNF{alpha}-promoted tumor. Bay 11-7082 blocked TNF{alpha} capacity to induce cell proliferation and up-regulation of cyclin D1 and of Bcl-x{sub L}in vivo and in vitro. Our results reveal evidence for TNF{alpha} as a breast tumor promoter, and provide novel data for a future therapeutic approach using TNF{alpha} antagonists and NF-{kappa}B pharmacological inhibitors in established breast cancer treatment.« less

Mena invasive (MenaINV) promotes multicellular streaming motility and transendothelial migration in a mouse model of breast cancer

PubMed Central

Roussos, Evanthia T.; Balsamo, Michele; Alford, Shannon K.; Wyckoff, Jeffrey B.; Gligorijevic, Bojana; Wang, Yarong; Pozzuto, Maria; Stobezki, Robert; Goswami, Sumanta; Segall, Jeffrey E.; Lauffenburger, Douglas A.; Bresnick, Anne R.; Gertler, Frank B.; Condeelis, John S.

2011-01-01

We have shown previously that distinct Mena isoforms are expressed in invasive and migratory tumor cells in vivo and that the invasion isoform (MenaINV) potentiates carcinoma cell metastasis in murine models of breast cancer. However, the specific step of metastatic progression affected by this isoform and the effects on metastasis of the Mena11a isoform, expressed in primary tumor cells, are largely unknown. Here, we provide evidence that elevated MenaINV increases coordinated streaming motility, and enhances transendothelial migration and intravasation of tumor cells. We demonstrate that promotion of these early stages of metastasis by MenaINV is dependent on a macrophage–tumor cell paracrine loop. Our studies also show that increased Mena11a expression correlates with decreased expression of colony-stimulating factor 1 and a dramatically decreased ability to participate in paracrine-mediated invasion and intravasation. Our results illustrate the importance of paracrine-mediated cell streaming and intravasation on tumor cell dissemination, and demonstrate that the relative abundance of MenaINV and Mena11a helps to regulate these key stages of metastatic progression in breast cancer cells. PMID:21670198

Collagen content as a risk factor in breast cancer? A pilot clinical study

NASA Astrophysics Data System (ADS)

Pifferi, Antonio; Quarto, Giovanna; Abbate, Francesca; Balestreri, Nicola; Menna, Simona; Cassano, Enrico; Cubeddu, Rinaldo; Taroni, Paola

2015-07-01

A retrospective pilot clinical study on time domain multi-wavelength (635 to 1060 nm) optical mammography was exploited to assess collagen as a breast-cancer risk factor on a total of 109 subjects (53 healthy and 56 with malignant lesions). An increased cancer occurrence is observed on the 15% subset of patients with higher age-matched collagen content. Further, a similar clustering based on the percentage breast density leads to a different set of patients, possibly indicating collagen as a new independent breast cancer risk factor. If confirmed statistically and on larger numbers, these results could have huge impact on personalized diagnostics, health care systems, as well as on basic research.

In Utero Influences, Breast Stem Cells, and Breast Cancer Risk Factors

DTIC Science & Technology

2011-08-01

predictor of human breast cancer risk. Our hypothesis is that the in utero levels of mitogens, such as insulin -like growth factor-1 (IGF-1), drive an...by histological assays and in vivo and explant imaging. Histologically, we stained mammary glands from virgin and pregnant C57BL/6J mice using whole...that of a E16 pregnant (right panel); both glands are from 8 week-old mice. Second, we performed preliminary studies to quantitate and validate

Potential Angiogenic Role of Platelet-Activating Factor in Human Breast Cancer

PubMed Central

Montrucchio, Giuseppe; Sapino, Anna; Bussolati, Benedetta; Ghisolfi, Gianpiero; Rizea-Savu, Simona; Silvestro, Luigi; Lupia, Enrico; Camussi, Giovanni

1998-01-01

This study investigated the presence of platelet-activating factor (PAF) in the lipid extracts of 18 primary breast carcinomas and 20 control breast tissues. The amount of PAF detected in breast carcinomas was significantly higher than in controls. The mass spectrometric analysis of PAF-bioactive lipid extract from breast carcinomas showed the presence of several molecular species of PAF, including C16-alkylPAF, C18-lysophosphatidylcholine (LPC), C16-LPC, lyso-PAF, and C16-acylPAF. The amount of bioactive PAF extracted from breast specimens significantly correlated with tumor vascularization revealed by the number of CD34- and CD31-positive cells. As C16-alkylPAF was previously shown to induce angiogenesis in vivo, we evaluated whether the thin layer chromatography-purified lipid extracts of breast specimens elicited neoangiogenesis in a murine model of subcutaneous Matrigel injection. The lipid extracts from specimens of breast carcinoma containing high levels of PAF bioactivity, but not from breast carcinomas containing low levels of PAF bioactivity or from normal breast tissue, induced a significant angiogenic response. This angiogenic response was significantly inhibited by the PAF receptor antagonist WEB 2170. T47D and MCF7 breast cancer cell lines, but not an immortalized nontumor breast cell line (MCF10), released PAF in the culture medium. A significant in vivo neoangiogenic response, inhibited by WEB 2170, was elicited by T47D and MCF7 but not by MCF10 culture medium. These results indicate that an increased concentration of PAF is present in tumors with high microvessel density and that PAF may account for the neoangiogenic activity induced in mice by the lipid extracts obtained from breast cancer. A contribution of PAF in the neovascularization of human breast cancer is suggested. PMID:9811351

Protection, promotion and support of breast-feeding in Europe: progress from 2002 to 2007.

PubMed

Cattaneo, Adriano; Burmaz, Tea; Arendt, Maryse; Nilsson, Ingrid; Mikiel-Kostyra, Krystyna; Kondrate, Irena; Communal, Marie José; Massart, Catherine; Chapin, Elise; Fallon, Maureen

2010-06-01

To assess progress in the protection, promotion and support of breast-feeding in Europe. Data for 2002 and 2007 were gathered with the same questionnaire. Of thirty countries, twenty-nine returned data for 2002, twenty-four for 2007. The number of countries with national policies complying with WHO recommendations increased. In 2007, six countries lacked a national policy, three a national plan, four a national breast-feeding coordinator and committee. Little improvement was reported in pre-service training; however, the number of countries with good coverage in the provision of WHO/UNICEF courses for in-service training increased substantially, as reflected in a parallel increase in the number of Baby Friendly Hospitals and the proportion of births taking place in them. Little improvement was reported as far as implementation of the International Code on Marketing of Breastmilk Substitutes is concerned. Except for Ireland and the UK, where some improvement occurred, no changes were reported on maternity protection. Due to lack of standard methods, it was difficult to compare rates of breast-feeding among countries. With this in mind, slight improvements in the rates of initiation, exclusivity and duration were reported by countries where data at two points in time were available. Breast-feeding rates continue to fall short of global recommendations. National policies are improving slowly but are hampered by the lack of action on maternity protection and the International Code. Pre-service training and standard monitoring of breast-feeding rates are the areas where more efforts are needed to accelerate progress.

[Primary care centers and breast-feeding].

PubMed

Nacher Fernández, A; Sanantonio Valdearcos, F; Barreda Simó, I; Palau Fuster, G; Palomares Gimeno, M J; Agramunt Soler, G; Fabregat Julve, I; Labordena Barceló, C

2001-09-01

To study activities that promote, maintain and support breast feeding in primary care centers in our health district and to evaluate the commitment of health center directors' to breast feeding, their knowledge of the subject, and programs involved in the promotion of natural breast-feeding. A cross-sectional study was carried out through surveys to those in charge of health centers, nursing, pediatric programs and pregnancy programs. Eighty surveys were sent to center and program directors. Answers were obtained from 66.2 %. A total of 6.9 % of the centers had no program or protocol for the promotion and maintenance of breast-feeding, nor did they seek the collaboration of support groups. Only 28.8 % of the centers surveyed carried out activities that provided special support to mothers with difficulties in breast-feeding. In contrast, 80.4 % possessed an adequate register on the incidence of breast-feeding. In 74.5 % of the centers, health professionals were given no specific training on the subject. Only 14.9 % of the centers had rules prohibiting visible leaflets, posters or samples of formula milk. In 84.6 % of the centers, no place was provided where breast-feeding could be carried out, observed, and possible problems corrected. Most of the primary care centers surveyed do not promote programmed activities favoring the promotion and maintenance of breast-feeding. Nevertheless, many centers provide advice on breast-feeding. Collaboration with support groups or other resources that might exist in the community is not generally sought. Specific training in breast-feeding is not given to the centers' health professionals. Only a minority of the centers possesses an appropriate place where mothers can breast-feed if they wish and where the process of breast-feeding can be observed and modified. The results suggest that primary care centers do not provide the necessary support to ensure successful breast-feeding and that they lack the resources necessary to achieve

Membrane Estrogen and HER-2 Receptors in Human Breast Cancer

DTIC Science & Technology

2002-07-01

activation of G-proteins, adenylate cyclase, inositol phosphate, calcium homeostasis and/or MAP kinase. These interactions may promote phosphorylation of ER...of breast cancer cells and interact with transmembrane HER-2 growth factor receptors. Expression of HER-2 receptors occurs in many breast cancers...reports of significant cross-talk and interaction between erb B (HER) pathways and estrogen receptor signaling (3,24,27,34-36). It is generally held

Determinants of stage at diagnosis of breast cancer in Nigerian women: sociodemographic, breast cancer awareness, health care access and clinical factors.

PubMed

Jedy-Agba, Elima; McCormack, Valerie; Olaomi, Oluwole; Badejo, Wunmi; Yilkudi, Monday; Yawe, Terna; Ezeome, Emmanuel; Salu, Iliya; Miner, Elijah; Anosike, Ikechukwu; Adebamowo, Sally N; Achusi, Benjamin; Dos-Santos-Silva, Isabel; Adebamowo, Clement

2017-07-01

Advanced stage at diagnosis is a common feature of breast cancer in Sub-Saharan Africa (SSA), contributing to poor survival rates. Understanding its determinants is key to preventing deaths from this cancer in SSA. Within the Nigerian Integrative Epidemiology of Breast Cancer Study, a multicentred case-control study on breast cancer, we studied factors affecting stage at diagnosis of cases, i.e. women diagnosed with histologically confirmed invasive breast cancer between January 2014 and July 2016 at six secondary and tertiary hospitals in Nigeria. Stage was assessed using clinical and imaging methods. Ordinal logistic regression was used to examine associations of sociodemographic, breast cancer awareness, health care access and clinical factors with odds of later stage (I, II, III or IV) at diagnosis. A total of 316 women were included, with a mean age (SD) of 45.4 (11.4) years. Of these, 94.9% had stage information: 5 (1.7%), 92 (30.7%), 157 (52.4%) and 46 (15.3%) were diagnosed at stages I, II, III and IV, respectively. In multivariate analyses, lower educational level (odds ratio (OR) 2.35, 95% confidence interval: 1.04, 5.29), not believing in a cure for breast cancer (1.81: 1.09, 3.01), and living in a rural area (2.18: 1.05, 4.51) were strongly associated with later stage, whilst age at diagnosis, tumour grade and oestrogen receptor status were not. Being Muslim (vs. Christian) was associated with lower odds of later stage disease (0.46: 0.22, 0.94). Our findings suggest that factors that are amenable to intervention concerning breast cancer awareness and health care access, rather than intrinsic tumour characteristics, are the strongest determinants of stage at diagnosis in Nigerian women.

Soluble L1CAM promotes breast cancer cell adhesion and migration in vitro, but not invasion.

PubMed

Li, Yupei; Galileo, Deni S

2010-09-15

Neural recognition molecule L1CAM, which is a key protein involved in early nervous system development, is known to be abnormally expressed and shed in several types of cancers where it participates in metastasis and progression. The distinction of L1CAM presence in cancerous vs. normal tissues has suggested it to be a new target for cancer treatment. Our current study focused on the potential role of soluble L1CAM in breast cancer cell adhesion to extracellular matrix proteins, migration, and invasion. We found L1 expression levels were correlated with breast cancer stage of progression in established data sets of clinical samples, and also were high in more metastatic breast cancer cell lines MDA-MB-231 and MDA-MB-435, but low in less migratory MDA-MB-468 cells. Proteolysis of L1 into its soluble form (sL1) was detected in cell culture medium from all three above cell lines, and can be induced by PMA activation. Over-expression of the L1 ectodomain in MDA-MB-468 cells by using a lentiviral vector greatly increased the amount of sL1 released by those cells. Concomitantly, cell adhesion to extracellular matrix and cell transmigration ability were significantly promoted, while cell invasion ability through Matrigel™ remained unaffected. On the other hand, attenuating L1 expression in MDA-MB-231 cells by using a shRNA lentiviral vector resulted in reduced cell-matrix adhesion and transmigration. Similar effects were also shown by monoclonal antibody blocking of the L1 extracellular region. Moreover, sL1 in conditioned cell culture medium induced a directional migration of MDA-MB-468 cells, which could be neutralized by antibody treatment. Our data provides new evidence for the function of L1CAM and its soluble form in promoting cancer cell adhesion to ECM and cell migration. Thus, L1CAM is validated further to be a potential early diagnostic marker in breast cancer progression and a target for breast cancer therapy.

Soluble L1CAM promotes breast cancer cell adhesion and migration in vitro, but not invasion

PubMed Central

2010-01-01

Background Neural recognition molecule L1CAM, which is a key protein involved in early nervous system development, is known to be abnormally expressed and shed in several types of cancers where it participates in metastasis and progression. The distinction of L1CAM presence in cancerous vs. normal tissues has suggested it to be a new target for cancer treatment. Our current study focused on the potential role of soluble L1CAM in breast cancer cell adhesion to extracellular matrix proteins, migration, and invasion. Results We found L1 expression levels were correlated with breast cancer stage of progression in established data sets of clinical samples, and also were high in more metastatic breast cancer cell lines MDA-MB-231 and MDA-MB-435, but low in less migratory MDA-MB-468 cells. Proteolysis of L1 into its soluble form (sL1) was detected in cell culture medium from all three above cell lines, and can be induced by PMA activation. Over-expression of the L1 ectodomain in MDA-MB-468 cells by using a lentiviral vector greatly increased the amount of sL1 released by those cells. Concomitantly, cell adhesion to extracellular matrix and cell transmigration ability were significantly promoted, while cell invasion ability through Matrigel™ remained unaffected. On the other hand, attenuating L1 expression in MDA-MB-231 cells by using a shRNA lentiviral vector resulted in reduced cell-matrix adhesion and transmigration. Similar effects were also shown by monoclonal antibody blocking of the L1 extracellular region. Moreover, sL1 in conditioned cell culture medium induced a directional migration of MDA-MB-468 cells, which could be neutralized by antibody treatment. Conclusions Our data provides new evidence for the function of L1CAM and its soluble form in promoting cancer cell adhesion to ECM and cell migration. Thus, L1CAM is validated further to be a potential early diagnostic marker in breast cancer progression and a target for breast cancer therapy. PMID:20840789

Reduced MUC4 expression is a late event in breast carcinogenesis and is correlated with increased infiltration of immune cells as well as promoter hypermethylation in invasive breast carcinoma.

PubMed

Cho, Jin Seong; Park, Min Ho; Lee, Ji Shin; Yoon, Jung Han

2015-01-01

Altered expression of MUC4 is associated with tumor progression and immune surveillance, but the potential involvement of MUC4 in breast carcinogenesis has not been rigorously assessed. Immunohistochemical staining with anti-MUC4 antibody was performed in a total of 324 patients with 26 normal breasts, 25 usual ductal hyperplasia, 76 ductal carcinoma in situ, and 198 invasive breast carcinoma (IBC) using tissue microarray. Immunohistochemical staining for CD8, CD57, and CD1a and methylation-specific polymerase chain reaction were also performed in IBC. Reduced MUC4 expression in IBC was significantly higher than in usual ductal hyperplasia and ductal carcinoma in situ (P<0.001 and P<0.01, respectively). Reduced MUC4 expression in IBC was significantly correlated with promoter hypermethylation (P<0.05). No association between MUC4 expression and patient outcomes was identified. Intratumoral CD8 T cells and stromal CD57 natural killer cells were significantly increased in the reduced MUC4 expression group compared with those in the normal expression group (P<0.01 and P<0.05, respectively). Our results suggest that tumor progression in breast epithelium is accompanied by reduced MUC4 protein expression. Reduced MUC4 expression correlates with increased tumor-infiltrating CD8 T and NK cells as well as promoter hypermethylation in IBC.

MicroRNA-9 promotes the proliferation, migration, and invasion of breast cancer cells via down-regulating FOXO1.

PubMed

Liu, D-Z; Chang, B; Li, X-D; Zhang, Q-H; Zou, Y-H

2017-09-01

The objective of the study was to investigate the role of microRNA-9 (miR-9) targeting forkhead box O1 (FOXO1) in the proliferation, migration, and invasion of breast cancer cells. Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to determine the expressions of miR-9 and FOXO1 mRNA in breast cancer tissues, normal breast tissues, breast cancer cell lines, and normal breast epithelial cells. After the up-regulation of miR-9 expression, qRT-PCR and Western blotting were used to determine the expression of FOXO1. The luciferase reporter gene assay was used to validate the target gene. The CCK-8 assay, scratch-wound healing assay, and Transwell invasion assay were used to investigate the changes in the proliferation, migration, and invasion of breast cancer cells, respectively. MicroRNA-9 expression was significantly up-regulated in breast cancer tissues and breast cancer cell lines when compared with normal breast tissues and normal breast epithelial cells (both P < 0.05). FOXO1 mRNA and protein expressions were substantially down-regulated in breast cancer tissues and breast cancer cell lines when compared with normal breast tissues and normal breast epithelial cells (both P < 0.05). There can be a negative correlation between miR-9 and FOXO1 mRNA in breast cancer. Luciferase reporter gene assay indicated that miR-9 can down-regulate FOXO1 expression at a post-transcriptional level through binding specifically to FOXO1 3'UTR. The results of CCK-8 assay, scratch-wound healing assay, and Transwell invasion assay revealed that the inhibition of miR-9 can suppress MCF7 cell proliferation, migration, and invasion. Additionally, the expression of miR-9 increased significantly whilst that of FOXO1 decreased substantially as the disease progressed (P < 0.05). Our study provides evidence that miR-9 can promote the proliferation, migration, and invasion of breast cancer cells via down-regulating FOXO1.