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Sample records for specific anti-breast cancer

  1. Biocatalytically Oligomerized Epicatechin with Potent and Specific Anti-proliferative Activity for Human Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Ramaswamy Nagarajan

    2008-11-01

    Full Text Available Catechins, naturally occurring flavonoids derived from wine and green tea, are known to exhibit multiple health benefits. Epigallocatechin gallate (EGCG is one of the most widely investigated catechins, but its efficacy in cancer therapy is still inconsistent and limited. The poor stability of EGCG has contributed to the disparity in the reported anti-cancer activity and other beneficial properties. Here we report an innovative enzymatic strategy for the oligomerization of catechins (specifically epicatechin that yields stable, water-soluble oligomerized epicatechins with enhanced and highly specific anti-proliferative activity for human breast cancer cells. This one-pot oxidative oligomerization is carried out in ambient conditions using Horseradish Peroxidase (HRP as a catalyst yielding water-soluble oligo(epicatechins. The oligomerized epicatechins obtained exhibit excellent growth inhibitory effects against human breast cancer cells with greater specificity towards growth-inhibiting cancer cells as opposed to normal cells, achieving a high therapeutic differential. Our studies indicate that water-soluble oligomeric epicatechins surpass EGCG in stability, selectivity and efficacy at lower doses.

  2. H2Mab-77 is a Sensitive and Specific Anti-HER2 Monoclonal Antibody Against Breast Cancer.

    Science.gov (United States)

    Itai, Shunsuke; Fujii, Yuki; Kaneko, Mika K; Yamada, Shinji; Nakamura, Takuro; Yanaka, Miyuki; Saidoh, Noriko; Chang, Yao-Wen; Handa, Saori; Takahashi, Maki; Suzuki, Hiroyoshi; Harada, Hiroyuki; Kato, Yukinari

    2017-08-01

    Human epidermal growth factor receptor 2 (HER2) plays a critical role in the progression of breast cancers, and HER2 overexpression is associated with poor clinical outcomes. Trastuzumab is an anti-HER2 humanized antibody that leads to significant survival benefits in patients with HER2-positive metastatic breast cancers. In this study, we developed novel anti-HER2 monoclonal antibodies (mAbs) and characterized their efficacy in flow cytometry, Western blot, and immunohistochemical analyses. Initially, we expressed the full length or ectodomain of HER2 in LN229 glioblastoma cells and then immunized mice with ectodomain of HER2 or LN229/HER2, and performed the first screening by enzyme-linked immunosorbent assays using ectodomain of HER2. Subsequently, we selected mAbs according to their efficacy in flow cytometry (second screening), Western blot (third screening), and immunohistochemical analyses (fourth screening). Among 100 mAb clones, only three mAbs reacted with HER2 in Western blot, and clone H 2 Mab-77 (IgG 1 , kappa) was selected. Finally, immunohistochemical analyses with H 2 Mab-77 showed sensitive and specific reactions against breast cancer cells, warranting the use of H 2 Mab-77 to detect HER2 in pathological analyses of breast cancers.

  3. Breast Cancer Immunotherapy

    Institute of Scientific and Technical Information of China (English)

    Juhua Zhou; Yin Zhong

    2004-01-01

    Breast cancer is a leading cause of cancer-related deaths in women worldwide. Although tumorectomy,radiotherapy, chemotherapy and hormone replacement therapy have been used for the treatment of breast cancer, there is no effective therapy for patients with invasive and metastatic breast cancer. Immunotherapy may be proved effective in treating patients with advanced breast cancer. Breast cancer immunotherapy includes antibody based immunotherapy, cancer vaccine immunotherapy, adoptive T cell transfer immunotherapy and T cell receptor gene transfer immunotherapy. Antibody based immunotherapy such as the monoclonal antibody against HER-2/neu (trastuzumab) is successfully used in the treatment of breast cancer patients with over-expressed HER-2/neu, however, HER-2/neu is over-expressed only in 25-30% of breast cancer patients. Cancer vaccine immunotherapy is a promising method to treat cancer patients. Cancer vaccines can be used to induce specific anti-tumor immunity in breast cancer patients, but cannot induce objective tumor regression. Adoptive T cell transfer immunotherapy is an effective method in the treatment of melanoma patients. Recent advances in anti-tumor T cell generation ex vivo and limited clinical trial data have made the feasibility of adoptive T cell transfer immunotherapy in the treatment of breast cancer patients. T cell receptor gene transfer can redirect the specificity of T cells. Chimeric receptor, scFv(anti-HER-2/neu)/zeta receptor, was successfully used to redirect cytotoxic T lymphocyte hybridoma cells to obtain anti-HER-2/neu positive tumor cells, suggesting the feasibility of treatment of breast cancer patients with T cell receptor gene transfer immunotherapy. Clinical trials will approve that immunotherapy is an effective method to cure breast cancer disease in the near future.

  4. Breast Cancer Immunotherapy

    Institute of Scientific and Technical Information of China (English)

    JuhuaZhou; YinZhong

    2004-01-01

    Breast cancer is a leading cause of cancer-related deaths in women worldwide. Although tumorectomy, radiotherapy, chemotherapy and hormone replacement therapy have been used for the treatment of breast cancer, there is no effective therapy for patients with invasive and metastatic breast cancer. Immunotherapy may be proved effective in treating patients with advanced breast cancer. Breast cancer immunotherapy includes antibody based immunotherapy, cancer vaccine immunotherapy, adoptive T cell transfer immunotherapy and T cell receptor gene transfer immunotherapy. Antibody based immunotherapy such as the monoclonal antibody against HER-2/neu (trastuzumab) is successfully used in the treatment of breast cancer patients with over-expressed HER-2/neu, however, HER-2/neu is over-expressed only in 25-30% of breast cancer patients. Cancer vaccine immunotherapy is a promising method to treat cancer patients. Cancer vaccines can be used to induce specific anti-tumor immunity in breast cancer patients, but cannot induce objective tumor regression. Adoptive T cell transfer immunotherapy is an effective method in the treatment of melanoma patients. Recent advances in anti-tumor T cell generation ex vivo and limited clinical trial data have made the feasibility of adoptive T cell transfer immunotherapy in the treatment of breast cancer patients. T cell receptor gene transfer can redirect the specificity of T cells. Chimeric receptor, scFv(anti-HER-2/neu)/zeta receptor, was successfully used to redirect cytotoxic T lymphocyte hybridoma cells to obtain anti-HER-2/neu positive tumor cells, suggesting the feasibility of treatment of breast cancer patients with T cell receptor gene transfer immunotherapy. Clinical trials will approve that immunotherapy is an effective method to cure breast cancer disease in the near future. Cellular & Molecular Immunology.

  5. A synthetic cryptochrome inhibitor induces anti-proliferative effects and increases chemosensitivity in human breast cancer cells

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    Chun, Sung Kook [Department of Brain & Cognitive Sciences, Daegu-Gyeongbuk Institute of Science & Technology, Daegu, 711-873 (Korea, Republic of); Department of Biological Sciences, Seoul National University, Seoul, 151-747 (Korea, Republic of); Department of Brain & Cognitive Sciences, Seoul National University, Seoul, 151-747 (Korea, Republic of); Chung, Sooyoung [Department of Biological Sciences, Seoul National University, Seoul, 151-747 (Korea, Republic of); Department of Biomedical Sciences, College of Medicine, Korea University, Seoul, 136-705 (Korea, Republic of); Kim, Hee-Dae [Department of Biological Sciences, Seoul National University, Seoul, 151-747 (Korea, Republic of); Lee, Ju Hyung [Department of Systems Biology, Yonsei University College of Life Science and Biotechnology, Seoul 120-749 (Korea, Republic of); Jang, Jaebong [College of Pharmacy, Seoul National University, Seoul, 151-742 (Korea, Republic of); Kim, Jeongah; Kim, Doyeon [Department of Brain & Cognitive Sciences, Daegu-Gyeongbuk Institute of Science & Technology, Daegu, 711-873 (Korea, Republic of); Department of Biological Sciences, Seoul National University, Seoul, 151-747 (Korea, Republic of); Department of Brain & Cognitive Sciences, Seoul National University, Seoul, 151-747 (Korea, Republic of); Son, Gi Hoon [Department of Biomedical Sciences, College of Medicine, Korea University, Seoul, 136-705 (Korea, Republic of); Oh, Young J. [Department of Systems Biology, Yonsei University College of Life Science and Biotechnology, Seoul 120-749 (Korea, Republic of); Suh, Young-Ger [College of Pharmacy, Seoul National University, Seoul, 151-742 (Korea, Republic of); Lee, Cheol Soon [Gachon Clinical Trials Center, Gachon University, Incheon, 417-842 (Korea, Republic of); and others

    2015-11-13

    Disruption of circadian rhythm is a major cause of breast cancer in humans. Cryptochrome (CRY), a circadian transcription factor, is a risk factor for initiation of breast cancer, and it is differentially expressed between normal and breast cancer tissues. Here, we evaluated the anti-proliferative and pro-apoptotic activity of KS15, a recently discovered small-molecule inhibitor of CRY, in human breast cancer cells. First, we investigated whether KS15 treatment could promote E-box-mediated transcription by inhibiting the activity of CRY in MCF-7 human breast cancer cells. Protein and mRNA levels of regulators of cell cycle and apoptosis, as well as core clock genes, were differentially modulated in response to KS15. Next, we investigated whether KS15 could inhibit proliferation and increase sensitivity to anti-tumor drugs in MCF-7 cells. We found that KS15 decreased the speed of cell growth and increased the chemosensitivity of MCF-7 cells to doxorubicin and tamoxifen, but had no effect on MCF-10A cells. These findings suggested that pharmacological inhibition of CRY by KS15 exerts an anti-proliferative effect and increases sensitivity to anti-tumor drugs in a specific type of breast cancer. - Highlights: • Cryptochrome inhibitor (KS15) has anti-tumor activity to human breast cancer cells. • KS15 induces differential changes in cell cycle regulators and pro-apoptotic genes. • KS15 inhibits MCF-7 cell growth and enhances susceptibility to anti-tumor drugs.

  6. A synthetic cryptochrome inhibitor induces anti-proliferative effects and increases chemosensitivity in human breast cancer cells

    International Nuclear Information System (INIS)

    Chun, Sung Kook; Chung, Sooyoung; Kim, Hee-Dae; Lee, Ju Hyung; Jang, Jaebong; Kim, Jeongah; Kim, Doyeon; Son, Gi Hoon; Oh, Young J.; Suh, Young-Ger; Lee, Cheol Soon

    2015-01-01

    Disruption of circadian rhythm is a major cause of breast cancer in humans. Cryptochrome (CRY), a circadian transcription factor, is a risk factor for initiation of breast cancer, and it is differentially expressed between normal and breast cancer tissues. Here, we evaluated the anti-proliferative and pro-apoptotic activity of KS15, a recently discovered small-molecule inhibitor of CRY, in human breast cancer cells. First, we investigated whether KS15 treatment could promote E-box-mediated transcription by inhibiting the activity of CRY in MCF-7 human breast cancer cells. Protein and mRNA levels of regulators of cell cycle and apoptosis, as well as core clock genes, were differentially modulated in response to KS15. Next, we investigated whether KS15 could inhibit proliferation and increase sensitivity to anti-tumor drugs in MCF-7 cells. We found that KS15 decreased the speed of cell growth and increased the chemosensitivity of MCF-7 cells to doxorubicin and tamoxifen, but had no effect on MCF-10A cells. These findings suggested that pharmacological inhibition of CRY by KS15 exerts an anti-proliferative effect and increases sensitivity to anti-tumor drugs in a specific type of breast cancer. - Highlights: • Cryptochrome inhibitor (KS15) has anti-tumor activity to human breast cancer cells. • KS15 induces differential changes in cell cycle regulators and pro-apoptotic genes. • KS15 inhibits MCF-7 cell growth and enhances susceptibility to anti-tumor drugs.

  7. Developing Anti-HER2 Vaccines: Breast Cancer Experience.

    Science.gov (United States)

    Al-Awadhi, Aydah; Murray, James Lee; Ibrahim, Nuhad K

    2018-04-25

    Breast cancer accounts for more than one million new cases annually and is the leading cause of death in women globally. HER2 overexpression induces cellular and humoral immune responses against the HER2 protein and is associated with higher tumour proliferation rates. Trastuzumab-based therapies are effectively and widely used as standard of care in HER2-amplified/overexpressed breast cancer patients; one cited mechanism of action is the induction of passive immunity and antibody-dependent cellular cytotoxicity against malignant breast cancer cells. These findings drove the efforts to generate antigen-specific immunotherapy to trigger the patient's immune system to target HER2-overexpressing tumour cells, which led to the development of various vaccines against the HER2 antigen. This manuscript discusses the various anti-HER2 vaccine formulations and strategies and their potential role in the metastatic and adjuvant settings. This article is protected by copyright. All rights reserved. © 2018 UICC.

  8. Amplexicaule A exerts anti-tumor effects by inducing apoptosis in human breast cancer

    Science.gov (United States)

    Shu, Guangwen; Wan, Dingrong; He, Feng; Loaec, Morgann; Ding, Yali; Li, Jun; Dovat, Sinisa; Yang, Gaungzhong; Song, Chunhua

    2016-01-01

    Chemotherapy is the main treatment for patients with breast cancer metastases, but natural alternatives have been receiving attention for their potential as novel anti-tumor reagents. Amplexicaule A (APA) is a flavonoid glucoside isolated from rhizomes of Polygonum amplexicaule D. Don var. sinense Forb (PADF). We found that APA has anti-tumor effects in a breast cancer xenograft mouse model and induces apoptosis in breast cancer cell lines. APA increased levels of cleaved caspase-3,-8,-9 and PARP, which resulted from suppression of MCL-1 and BCL-2 expression in the cells. APA also inactivated the Akt/mTOR pathway in breast cancer cells. Thus, APA exerts a strong anti-tumor effect on breast cancer cells, most likely through induction of apoptosis. Our study is the first to identify this novel anti-tumor compound and provides a new strategy for isolation and separation of single compounds from herbs. PMID:26943775

  9. Amplexicaule A exerts anti-tumor effects by inducing apoptosis in human breast cancer

    OpenAIRE

    Xiang, Meixian; Su, Hanwen; Shu, Guangwen; Wan, Dingrong; He, Feng; Loaec, Morgann; Ding, Yali; Li, Jun; Dovat, Sinisa; Yang, Gaungzhong; Song, Chunhua

    2016-01-01

    Chemotherapy is the main treatment for patients with breast cancer metastases, but natural alternatives have been receiving attention for their potential as novel anti-tumor reagents. Amplexicaule A (APA) is a flavonoid glucoside isolated from rhizomes of Polygonum amplexicaule D. Don var. sinense Forb (PADF). We found that APA has anti-tumor effects in a breast cancer xenograft mouse model and induces apoptosis in breast cancer cell lines. APA increased levels of cleaved caspase-3,-8,-9 and ...

  10. Molecular Mechanisms of Breast Cancer Metastasis and Potential Anti-metastatic Compounds.

    Science.gov (United States)

    Tungsukruthai, Sucharat; Petpiroon, Nalinrat; Chanvorachote, Pithi

    2018-05-01

    Throughout the world, breast cancer is among the major causes of cancer-related death and is the most common cancer found in women. The development of cancer molecular knowledge has surpassed the novel concept of cancer biology and unraveled principle targets for anticancer drug developments and treatment strategies. Metastatic breast cancer cells acquire their aggressive features through several mechanisms, including augmentation of survival, proliferation, tumorigenicity, and motility-related cellular pathways. Clearly, natural product-derived compounds have since long been recognized as an important source for anticancer drugs, several of which have been shown to have promising anti-metastasis activities by suppressing key molecular features supporting such cell aggressiveness. This review provides the essential details of breast cancer, the molecular-based insights into metastasis, as well as the effects and mechanisms of potential compounds for breast cancer therapeutic approaches. As the abilities of cancer cells to invade and metastasize are addressed as the hallmarks of cancer, compounds possessing anti-metastatic effects, together with their defined molecular drug action could benefit the development of new drugs as well as treatment strategies. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  11. Chemotherapy and radiation therapy elicits tumor specific T cell responses in a breast cancer patient

    International Nuclear Information System (INIS)

    Bernal-Estévez, David; Sánchez, Ramiro; Tejada, Rafael E.; Parra-López, Carlos

    2016-01-01

    Experimental evidence and clinical studies in breast cancer suggest that some anti-tumor therapy regimens generate stimulation of the immune system that accounts for tumor clinical responses, however, demonstration of the immunostimulatory power of these therapies on cancer patients continues to be a formidable challenge. Here we present experimental evidence from a breast cancer patient with complete clinical response after 7 years, associated with responsiveness of tumor specific T cells. T cells were obtained before and after anti-tumor therapy from peripheral blood of a 63-years old woman diagnosed with ductal breast cancer (HER2/neu+++, ER-, PR-, HLA-A*02:01) treated with surgery, followed by paclitaxel, trastuzumab (suspended due to cardiac toxicity), and radiotherapy. We obtained a leukapheresis before surgery and after 8 months of treatment. Using in vitro cell cultures stimulated with autologous monocyte-derived dendritic cells (DCs) that produce high levels of IL-12, we characterize by flow cytometry the phenotype of tumor associated antigens (TAAs) HER2/neu and NY-ESO 1 specific T cells. The ex vivo analysis of the TCR-Vβ repertoire of TAA specific T cells in blood and Tumor Infiltrating Lymphocytes (TILs) were performed in order to correlate both repertoires prior and after therapy. We evidence a functional recovery of T cell responsiveness to polyclonal stimuli and expansion of TAAs specific CD8+ T cells using peptide pulsed DCs, with an increase of CTLA-4 and memory effector phenotype after anti-tumor therapy. The ex vivo analysis of the TCR-Vβ repertoire of TAA specific T cells in blood and TILs showed that whereas the TCR-Vβ04-02 clonotype is highly expressed in TILs the HER2/neu specific T cells are expressed mainly in blood after therapy, suggesting that this particular TCR was selectively enriched in blood after anti-tumor therapy. Our results show the benefits of anti-tumor therapy in a breast cancer patient with clinical complete response in

  12. Moringa oleifera as an Anti-Cancer Agent against Breast and Colorectal Cancer Cell Lines.

    Science.gov (United States)

    Al-Asmari, Abdulrahman Khazim; Albalawi, Sulaiman Mansour; Athar, Md Tanwir; Khan, Abdul Quaiyoom; Al-Shahrani, Hamoud; Islam, Mozaffarul

    2015-01-01

    In this study we investigated the anti-cancer effect of Moringa oleifera leaves, bark and seed extracts. When tested against MDA-MB-231 and HCT-8 cancer cell lines, the extracts of leaves and bark showed remarkable anti-cancer properties while surprisingly, seed extracts exhibited hardly any such properties. Cell survival was significantly low in both cells lines when treated with leaves and bark extracts. Furthermore, a striking reduction (about 70-90%) in colony formation as well as cell motility was observed upon treatment with leaves and bark. Additionally, apoptosis assay performed on these treated breast and colorectal cancer lines showed a remarkable increase in the number of apoptotic cells; with a 7 fold increase in MD-MB-231 to an increase of several fold in colorectal cancer cell lines. However, no significant apoptotic cells were detected upon seeds extract treatment. Moreover, the cell cycle distribution showed a G2/M enrichment (about 2-3 fold) indicating that these extracts effectively arrest the cell progression at the G2/M phase. The GC-MS analyses of these extracts revealed numerous known anti-cancer compounds, namely eugenol, isopropyl isothiocynate, D-allose, and hexadeconoic acid ethyl ester, all of which possess long chain hydrocarbons, sugar moiety and an aromatic ring. This suggests that the anti-cancer properties of Moringa oleifera could be attributed to the bioactive compounds present in the extracts from this plant. This is a novel study because no report has yet been cited on the effectiveness of Moringa extracts obtained in the locally grown environment as an anti-cancer agent against breast and colorectal cancers. Our study is the first of its kind to evaluate the anti-malignant properties of Moringa not only in leaves but also in bark. These findings suggest that both the leaf and bark extracts of Moringa collected from the Saudi Arabian region possess anti-cancer activity that can be used to develop new drugs for treatment of breast

  13. Antiproliferative and apoptotic effects of a specific anti-insulin-like growth factor I receptor single chain antibody on breast cancer cells.

    Science.gov (United States)

    Motallebnezhad, Morteza; Younesi, Vahid; Aghebati-Maleki, Leili; Nickho, Hamid; Safarzadeh, Elham; Ahmadi, Majid; Movassaghpour, Ali Akbar; Hosseini, Ahmad; Yousefi, Mehdi

    2016-11-01

    Insulin-like growth factor I receptor (IGF-IR) is expressed on breast cancer cells and involves in metastasis, survival, and proliferation. Currently, application of IGF-IR-targeting monoclonal antibodies (mAbs), alone or in combination with other drugs, is a promising strategy for breast cancer therapy. Single-chain fragment variable (scFv) antibodies have been introduced as appropriate tools for tumor-targeting purposes because of their advantages over whole antibodies. In the present study, we employed a naïve phage library and isolated scFvs against a specific epitope from extracellular domain of IGF-IR by panning process. The selected scFvs were further characterized using polyclonal and monoclonal phage ELISA, soluble monoclonal ELISA, and colony PCR and sequencing. Antiproliferative and apoptotic effects of selected scFv antibodies on breast cancer cell lines were also evaluated by MTT and Annexin V/PI assays. The results of ELISA indicated specific reactions of the isolated scFvs against the IGF-IR peptide, and analyses of PCR product and sequencing confirmed the presence of full length V H and Vκ inserts. Treatment of MCF7 and SKBR3 cells with anti-IGF-IR scFv led to a significant growth inhibition. The results also showed that scFv treatment significantly augmented trastuzumab growth inhibitory effects on SKBR3 cells. The percentage of the apoptotic MCF7 and SKBR3 cells after 24-h treatment with scFv was 39 and 30.70 %, respectively. Twenty-four-hour treatment with scFv in combination with trastuzumab resulted in 44.75 % apoptosis of SKBR3 cells. Taken together, our results demonstrate that the targeting of IGF-IR by scFv can be an effective strategy in the treatment of breast cancer and provide further evidence for effectiveness of dual targeting of HER2 and IGF-IR in breast cancer therapy.

  14. Low penetrance breast cancer susceptibility loci are associated with specific breast tumor subtypes

    DEFF Research Database (Denmark)

    Broeks, Annegien; Schmidt, Marjanka K; Sherman, Mark E

    2011-01-01

    Breast cancers demonstrate substantial biological, clinical and etiological heterogeneity. We investigated breast cancer risk associations of eight susceptibility loci identified in GWAS and two putative susceptibility loci in candidate genes in relation to specific breast tumor subtypes. Subtype...... stratification might help in the identification and characterization of novel risk factors for breast cancer subtypes. This may eventually result in further improvements in prevention, early detection and treatment.......Breast cancers demonstrate substantial biological, clinical and etiological heterogeneity. We investigated breast cancer risk associations of eight susceptibility loci identified in GWAS and two putative susceptibility loci in candidate genes in relation to specific breast tumor subtypes. Subtypes...... were defined by five markers (ER, PR, HER2, CK5/6, EGFR) and other pathological and clinical features. Analyses included up to 30 040 invasive breast cancer cases and 53 692 controls from 31 studies within the Breast Cancer Association Consortium. We confirmed previous reports of stronger associations...

  15. Boswellia sacra essential oil induces tumor cell-specific apoptosis and suppresses tumor aggressiveness in cultured human breast cancer cells

    Science.gov (United States)

    2011-01-01

    Background Gum resins obtained from trees of the Burseraceae family (Boswellia sp.) are important ingredients in incense and perfumes. Extracts prepared from Boswellia sp. gum resins have been shown to possess anti-inflammatory and anti-neoplastic effects. Essential oil prepared by distillation of the gum resin traditionally used for aromatic therapy has also been shown to have tumor cell-specific anti-proliferative and pro-apoptotic activities. The objective of this study was to optimize conditions for preparing Boswellea sacra essential oil with the highest biological activity in inducing tumor cell-specific cytotoxicity and suppressing aggressive tumor phenotypes in human breast cancer cells. Methods Boswellia sacra essential oil was prepared from Omani Hougari grade resins through hydrodistillation at 78 or 100 oC for 12 hours. Chemical compositions were identified by gas chromatography-mass spectrometry; and total boswellic acids contents were quantified by high-performance liquid chromatography. Boswellia sacra essential oil-mediated cell viability and death were studied in established human breast cancer cell lines (T47D, MCF7, MDA-MB-231) and an immortalized normal human breast cell line (MCF10-2A). Apoptosis was assayed by genomic DNA fragmentation. Anti-invasive and anti-multicellular tumor properties were evaluated by cellular network and spheroid formation models, respectively. Western blot analysis was performed to study Boswellia sacra essential oil-regulated proteins involved in apoptosis, signaling pathways, and cell cycle regulation. Results More abundant high molecular weight compounds, including boswellic acids, were present in Boswellia sacra essential oil prepared at 100 oC hydrodistillation. All three human breast cancer cell lines were sensitive to essential oil treatment with reduced cell viability and elevated cell death, whereas the immortalized normal human breast cell line was more resistant to essential oil treatment. Boswellia sacra

  16. NY-BR-1 Antigen Expression and anti-NY-BR-1 IgG in Egyptian Breast Cancer Patients: Clinicopathological and Prognostic Significance.

    Science.gov (United States)

    Abu El-Nazar, Salma Y; Ghazy, Amany A; Ghoneim, Hossam E; Zoheir, Malak; Ahmed, Ahmed S; Sorour, Sally S; Abouelella, Amira M

    2015-01-01

    Breast cancer is the most common gynecological malignancy in the world. In Egypt, it ranks the first among female malignancies with incidence of 37.7%. Over the last decades, the integration of prognostic and predictive markers in treatment decisions has led to more individualized and optimized therapy. NY-BR-1 antigen has been shown to be frequently expressed in breast cancers. The study aimed to assess the tissue expression of NY-BR-1 antigen and serum IgG antibody to this antigen in Egyptian breast cancer females. The study was conducted on 60 females (10 healthy, 10 having benign breast lesions, 40 with malignant breast cancer). NY-BR-1 Ag expression was evaluated by immunohistochemistry and anti-NY-BR-1 IgG was assessed by ELISA. Results revealed a significant difference in NY-BR-1 Ag expression between benign and malignant breast cancer patients. There was a significant correlation between NY-BR-1 antigen expression and estrogen receptor's status (P = 0.019), stage of the disease (P = 0.008), menopausal status (P = 0.008), lymph node involvement (P = 0.022) and anti-NY-BR-1 IgG (P = 0.032) among the studied individuals. In addition, there was a statistically significant increase in anti-NY-BR-1 IgG O.D. results among malignant breast cancer group. It is correlated with tumor type (P < 0.001) and progesterone receptor status (P = 0.038). In conclusion, our work may represent a step towards identification of a new prognostic marker specific for breast cancer.

  17. Common germline polymorphisms associated with breast cancer-specific survival

    DEFF Research Database (Denmark)

    Pirie, Ailith; Guo, Qi; Kraft, Peter

    2015-01-01

    in the meta-analysis. Fifty-four of these were evaluated in the full set of 37,954 breast cancer cases with 2,900 events and the two additional variants were evaluated in a reduced sample size of 30,000 samples in order to ensure independence from the previously published studies. Five variants reached...... evaluated in the pooled analysis of over 37,000 breast cancer cases for association with breast cancer-specific survival. Previous associations were evaluated using a one-sided test based on the reported direction of effect. RESULTS: Fifty-six variants from 45 previous publications were evaluated......-specific survival using data from a pooled analysis of eight breast cancer survival genome-wide association studies (GWAS) from the Breast Cancer Association Consortium. METHODS: A literature review was conducted of all previously published associations between common germline variants and three survival outcomes...

  18. HER2-positive breast cancer, how far away from the cure?-on the current situation of anti-HER2 therapy in breast cancer treatment and survival of patients.

    Science.gov (United States)

    Liao, Ning

    2016-06-01

    With the diagnosis and treatment of tumor enter into the area of precision medical, based on selected targeted molecular typing of patients with individualized diagnosis and treatment play an important role. HER gene encoded epidermal growth factor receptor 2 (HER2) leading to increased early distant metastasis of breast cancer in patients and poor prognosis. However, a number of clinical studies provided evidence-based anti-HER2 targeted therapy and confirmed the benefit of anti-HER2 targeted therapy in patient survival. In recent years, through the tireless efforts of scholars in the field of breast cancer in our country, the whole diagnosis and treatment of breast cancer has accomplished an international standard. But based on a variety of factors, the anti-HER2 targeted therapy between China and the developed countries, and between different areas in China still exists certain gaps, is now a problem need to be solved. This article will analyzing the diagnostic and treatment on HER2-positive breast cancer in the United States and China, exploring reasons and looking for answers to narrow down the gap in the treatment of HER2-positive breast cancer between China and the United States. Improve the anti-HER2 targeted therapy in our country, let the patients get maximum benefit from anti-HER2 targeted therapy.

  19. CHEK2*1100delC Heterozygosity in Women With Breast Cancer Associated With Early Death, Breast Cancer-Specific Death, and Increased Risk of a Second Breast Cancer

    DEFF Research Database (Denmark)

    Weischer, Maren; Nordestgaard, Børge G; Pharoah, Paul

    2012-01-01

    PURPOSE We tested the hypotheses that CHEK2*1100delC heterozygosity is associated with increased risk of early death, breast cancer-specific death, and risk of a second breast cancer in women with a first breast cancer. PATIENTS AND METHODS From 22 studies participating in the Breast Cancer Assoc...

  20. Anti-EGFR Therapy: Mechanism and Advances in Clinical Efficacy in Breast Cancer

    Directory of Open Access Journals (Sweden)

    John F. Flynn

    2009-01-01

    Full Text Available This review will focus on recent advances in the application of antiepidermal growth factor receptor (anti-EGFR for the treatment of breast cancer. The choice of EGFR, a member of the ErbB tyrosine kinase receptor family, stems from evidence pinpointing its role in various anti-EGFR therapies. Therefore, an increase in our understanding of EGFR mechanism and signaling might reveal novel targets amenable to intervention in the clinic. This knowledge base might also improve existing medical treatment options and identify research gaps in the design of new therapeutic agents. While the approved use of drugs like the dual kinase inhibitor Lapatinib represents significant advances in the clinical management of breast cancer, confirmatory studies must be considered to foster the use of anti-EGFR therapies including safety, pharmacokinetics, and clinical efficacy.

  1. Restoring Lost Anti-HER-2 Th1 Immunity in Breast Cancer: A Crucial Role for Th1 Cytokines in Therapy and Prevention.

    Science.gov (United States)

    Nocera, Nadia F; Lee, M Catherine; De La Cruz, Lucy M; Rosemblit, Cinthia; Czerniecki, Brian J

    2016-01-01

    The ErbB/B2 (HER-2/neu) oncogene family plays a critical role in the development and metastatic spread of several tumor types including breast, ovarian and gastric cancer. In breast cancer, HER-2/neu is expressed in early disease development in a large percentage of DCIS lesions and its expression is associated with an increased risk of invasion and recurrence. Targeting HER-2 with antibodies such as trastuzumab or pertuzumab has improved survival, but patients with more extensive disease may develop resistance to therapy. Interestingly, response to HER-2 targeted therapies correlates with presence of immune response genes in the breast. Th1 cell production of the cytokines interferon gamma (IFNγ) and TNFα can enhance MHC class I expression, PD-L1 expression, augment apoptosis and tumor senescence, and enhances growth inhibition of many anti-breast cancer agents, including anti-estrogens and HER-2 targeted therapies. Recently, we have identified that a loss of anti-HER-2 CD4 Th1 in peripheral blood occurs during breast tumorigenesis and is dramatically diminished, even in Stage I breast cancers. The loss of anti-HER-2 Th1 response is specific and not readily reversed by standard therapies. In fact, this loss of anti-HER-2 Th1 response in peripheral blood correlates with lack of complete response to neoadjuvant therapy and diminished disease-free survival. This defect can be restored with HER-2 vaccinations in both DCIS and IBC. Correcting the anti-HER-2 Th1 response may have significant impact in improving response to HER-2 targeted therapies. Development of immune monitoring systems for anti-HER-2 Th1 to identify patients at risk for recurrence could be critical to improving outcomes, since the anti-HER-2 Th1 response can be restored by vaccination. Correction of the cellular immune response against HER-2 may prevent recurrence in high-risk patients with DCIS and IBC at risk of developing new or recurrent breast cancer.

  2. Nonsteroidal anti-inflammatory drug use and breast cancer risk: a Danish cohort study

    DEFF Research Database (Denmark)

    Friis, Søren; Thomassen, Lars; Sørensen, Henrik T

    2008-01-01

    Epidemiologic studies investigating the effects of nonsteroidal anti-inflammatory drugs (NSAIDs) on breast cancer have yielded conflicting results. We examined the association between use of aspirin and nonaspirin NSAIDs and breast cancer risk among 28 695 women in the Danish Diet, Cancer...... and Health cohort. Information on NSAID and paracetamol use was obtained from a self-administered questionnaire completed at baseline (1993-1997) and updated through 2003 using a nationwide prescription database. Detailed information on breast cancer incidence and tumour characteristics was obtained from...... nationwide health registers. Cox proportional hazards regression was used to compute incidence rate ratios (RRs) and 95% confidence intervals (CIs). We identified 847 breast cancer cases over an average follow-up period of 7.5 years. Any NSAID use at baseline was associated with an increased incidence...

  3. Curcumin-docetaxel co-loaded nanosuspension for enhanced anti-breast cancer activity.

    Science.gov (United States)

    Sahu, Bhanu P; Hazarika, Hemanga; Bharadwaj, Rituraj; Loying, Pojul; Baishya, Rinku; Dash, Suvakanta; Das, Malay K

    2016-08-01

    A curcumin-docetaxel co-loaded nanosuspension with increased anti-breast cancer activity was developed. Curcumin is a potential anticancer agent with p-glycoprotein (p-gp) inhibiting activity may be co-administered with docetaxel as a nanosuspension to enhance its anticancer effect by increasing the oral bioavailability and decreasing drug efflux. Nanosuspensions of curcumin and docetaxel were prepared by precipitation-homozenisation technique and evaluated for particle size, polydispersity, zeta potential and drug release. The in vitro MTT assay was conducted using MCF-7 for anti-breast cancer activity. The in vivo biodistribution by radiolabeling and tumor inhibition study was conducted in mice. Homogenous nanosuspensions of 80 ± 20 nm were obtained with increased solubility. The drugs as nanosuspensions showed higher cytotoxicity on MCF-7 cell line compared to their suspensions due to the increased in vitro cellular uptake. Due to this increased solubility, sensitization of tumor cells and inhibition of p-gp the in-vivo results showed greater tumor inhibition rate of up to 70% in MCF-7 treated mice. Histopathological results showed higher apoptotic activity and reduced level of angiogenesis. The in vitro and in vivo study of the nanosuspensions has shown that Co-administration of Curcumin as a p-gp inhibitor with docetaxel may have the potential to increase the anti-breast cancer efficacy of both drugs.

  4. Melatonin: an Inhibitor of Breast Cancer

    Science.gov (United States)

    Hill, Steven M.; Belancio, Victoria P.; Dauchy, Robert T.; Xiang, Shulin; Brimer, Samantha; Mao, Lulu; Hauch, Adam; Lundberg, Peter W.; Summers, Whitney; Yuan, Lin; Frasch, Tripp; Blask, David E.

    2015-01-01

    This review discusses recent work on melatonin-mediated circadian regulation and metabolic and molecular signaling mechanisms involved in human breast cancer growth and associated consequences of circadian disruption by exposure to light at night (LEN). The anti-cancer actions of the circadian melatonin signal in human breast cancer cell lines and xenografts heavily involve MT1 receptor-mediated mechanisms. In estrogen receptor alpha (ERα)-positive human breast cancer, melatonin, via the MT1 receptor, suppresses ERα mRNA expression and ERα transcriptional activity. As well, melatonin regulates the transactivation of other members of the nuclear receptor super-family, estrogen metabolizing enzymes, and the expression of core clock and clock-related genes. Furthermore, melatonin also suppresses tumor aerobic metabolism (Warburg effect), and, subsequently, cell-signaling pathways critical to cell proliferation, cell survival, metastasis, and drug resistance. Melatonin demonstrates both cytostatic and cytotoxic activity in breast cancer cells that appears to be cell type specific. Melatonin also possesses anti-invasive/anti-metastatic actions that involve multiple pathways including inhibition of p38 MAPK and repression of epithelial-to-mesenchymal transition. Studies demonstrate that melatonin promotes genomic stability by inhibiting the expression of LINE-1 retrotransposons. Finally, research in animal and human models indicate that LEN induced disruption of the circadian nocturnal melatonin signal promotes the growth, metabolism, and signaling of human breast cancer to drive breast tumors to endocrine and chemotherapeutic resistance. These data provide the strongest understanding and support of the mechanisms underpinning the epidemiologic demonstration of elevated breast cancer risk in night shift workers and other individuals increasingly exposed to LEN. PMID:25876649

  5. Polymer–lipid hybrid anti-HER2 nanoparticles for targeted salinomycin delivery to HER2-positive breast cancer stem cells and cancer cells

    Directory of Open Access Journals (Sweden)

    Li J

    2017-09-01

    Full Text Available Jun Li,1,* Wenqing Xu,2,* Xiaoli Yuan,3,* Huaiwen Chen,3 Hao Song,1,4 Bingquan Wang,5 Jun Han5 1College of Pharmacy, Liaocheng University, Liaocheng, Shandong, 2Railway Police College, Zhengzhou, 3Department of Cadre Health Care, Nanjing General Hospital of Nanjing Military Command, Nanjing, Jiangsu, 4Centre for Stem Cell & Regenerative Medicine, Liaocheng People’s Hospital, 5Institute of Biopharmaceutical Research, Liaocheng University, Liaocheng, Shandong, China *These authors contributed equally to this work Purpose: Breast cancer stem cells (CSCs are responsible for the initiation, recurrence, and metastasis of breast cancer. Sufficient evidence has established that breast cancer cells can spontaneously turn into breast CSCs. Thus, it is essential to simultaneously target breast CSCs and cancer cells to maximize the efficacy of breast cancer therapy. HER2 has been found to be overexpressed in both breast CSCs and cancer cells. We developed salinomycin-loaded polymer–lipid hybrid anti-HER2 nanoparticles (Sali-NP-HER2 to target both HER2-positive breast CSCs and cancer cells.Methods: The antitumor activity of Sali-NP-HER2 constructed by conjugating anti-HER2 antibodies to polymer–lipid salinomycin nanoparticles was evaluated in vitro and in vivo.Results: Sali-NP-HER2 efficiently bound to HER2-positive breast CSCs and cancer cells, resulting in enhanced cytotoxic effects compared with non-targeted nanoparticles or salinomycin. In mice bearing breast cancer xenografts, administration of Sali-NP-HER2 exhibited superior efficacy in inhibiting tumor growth. Sali-NP-HER2 reduced the breast tumorsphere formation rate and the proportion of breast CSCs more effectively than non-targeted nanoparticles or salinomycin alone.Conclusion: Sali-NP-HER2 represents a promising approach in treating HER2-positive breast cancer by targeting both breast CSCs and cancer cells. Keywords: nanoparticles, breast cancer, cancer stem cells, salinomycin, HER2

  6. Breast cancer in systemic lupus

    DEFF Research Database (Denmark)

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

    2017-01-01

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

  7. Influence of specific comorbidities on survival after early-stage breast cancer

    DEFF Research Database (Denmark)

    Ewertz, Marianne; Land, Lotte Holm; Dalton, Susanne Oksbjerg

    2018-01-01

    elevated for patients with prior myocardial infarction, congestive heart failure, cerebrovascular disease, connective tissue disease, ulcer disease, and diabetes. The similar effect of adjuvant treatment in patients with and without comorbidity underlines the importance of adhering to guideline therapy.......BACKGROUND: While comorbidity indices are useful for describing trends in survival, information on specific comorbidities is needed for the clinician advising the individual breast cancer patient on her treatment. Here we present an analysis of overall survival, breast cancer-specific mortality......, and effect of medical adjuvant treatment among breast cancer patients suffering from 12 major comorbidities compared with breast cancer patients without comorbidities. MATERIAL AND METHODS: The study population was identified from the Danish Breast Cancer Cooperative Group and included 59,673 women without...

  8. External influences and priority-setting for anti-cancer agents: a case study of media coverage in adjuvant trastuzumab for breast cancer

    Directory of Open Access Journals (Sweden)

    Fralick John

    2007-06-01

    Full Text Available Abstract Background Setting priorities for the funding of new anti-cancer agents is becoming increasingly complex. The funding of adjuvant trastuzumab for breast cancer has brought this dilemma to the fore. In this paper we review external factors that may influence decision-making bodies and present a case study of media response in Ontario, Canada to adjuvant trastuzumab for breast cancer. Methods A comprehensive search of the databases of Canadian national and local newspapers and television was performed. Articles pertaining to trastuzumab in adjuvant breast cancer as well as 17 other anti-cancer drugs and indications were retrieved. The search period was from the date when individual trial results were announced to the date funding was made available in Ontario. Results During the 2.6 months between the release of the trastuzumab results to funding approval in Ontario, we identified 51 episodes of media coverage. For the 17 other drugs/indications (7 breast and 10 non-breast, the median time to funding approval was 31 months (range 14–46. Other recent major advances in oncology such as adjuvant vinorelbine/cisplatin for resected NSCLC and docetaxel for advanced prostate cancer received considerably less media attention (17 media reports for each than trastuzumab. The median number of media reports for breast cancer drugs was 4.5 compared to 2.5 for non-breast cancer drugs (p = 0.56. Conclusion Priority-setting for novel anti-cancer agents is a complex process that tries to ensure fair use of constrained resources to fund therapies with the best evidence of clinical benefit. However, this process is subject to external factors including the influence of media, patient advocates, politicians, and industry. The data in this case study serve to illustrate the significant involvement one (or all of these external factors may play in the debate over priority-setting.

  9. Anti-metastasis activity of black rice anthocyanins against breast cancer: analyses using an ErbB2 positive breast cancer cell line and tumoral xenograft model.

    Science.gov (United States)

    Luo, Li-Ping; Han, Bin; Yu, Xiao-Ping; Chen, Xiang-Yan; Zhou, Jie; Chen, Wei; Zhu, Yan-Feng; Peng, Xiao-Li; Zou, Qiang; Li, Sui-Yan

    2014-01-01

    Increasing evidence from animal, epidemiological and clinical investigations suggest that dietary anthocyanins have potential to prevent chronic diseases, including cancers. It is also noteworthy that human epidermal growth factor receptor 2 (ErbB2) protein overexpression or ErbB2 gene amplification has been included as an indicator for metastasis and higher risk of recurrence for breast cancer. The present experiments investigated the anti-metastasis effects of black rice anthocyanins (BRACs) on ErbB2 positive breast cancer cells in vivo and in vitro. Oral administration of BRACs (150 mg/kg/day) reduced transplanted tumor growth, inhibited pulmonary metastasis, and decreased lung tumor nodules in BALB/c nude mice bearing ErbB2 positive breast cancer cell MDA-MB-453 xenografts. The capacity for migration, adhesion, motility and invasion was also inhibited by BRACs in MDA-MB-453 cells in a concentration dependent manner, accompanied by decreased activity of a transfer promoting factor, urokinase-type plasminogen activator (u-PA). Together, our results indicated that BRACs possess anti-metastasis potential against ErbB2 positive human breast cancer cells in vivo and in vitro through inhibition of metastasis promoting molecules.

  10. Current therapeutic strategies of anti-HER2 treatment in advanced breast cancer patients

    Directory of Open Access Journals (Sweden)

    Joanna Huszno

    2016-03-01

    Full Text Available The HER2/neu ( ERBB2 oncogene is amplified and/or overexpressed in approximately 20% of breast cancers, and is a strong prognostic factor for relapse and poor overall survival, particularly in node-positive patients. It is also an important predictor for response to trastuzumab, which has established efficacy against breast cancer with overexpression or amplification of the HER2 oncogene. Treatment with the anti-HER2 humanized monoclonal antibody – trastuzumab significantly improves progression-free and overall survival among patients with HER2-positive breast cancer. However, in most patients with HER2-positive metastatic breast cancer, the disease progresses occurred, what cause the need for new targeted therapies for advanced disease. In clinical trials, there are tested new drugs to improve the results of treatment for this group of patients. This paper presents new drugs introduced into clinical practice for treatment of advanced breast cancer, whose molecular target are receptors of the HER2 family. In addition, new therapeutic strategies and drugs that are currently in clinical researches are discussed.

  11. Anti-tumor effects of everolimus and metformin are complementary and glucose-dependent in breast cancer cells

    NARCIS (Netherlands)

    Ariaans, Gerke; Jalving, Mathilde; de Vries, Emma Geertruida Elisabeth; de Jong, Steven

    2017-01-01

    Background: Clinical efficacy of the mTOR inhibitor everolimus is limited in breast cancer and regularly leads to side-effects including hyperglycemia. The AMPK inhibitor and anti-diabetic drug metformin may counteract everolimus-induced hyperglycemia, as well as enhancing anti-cancer efficacy. We

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

    Directory of Open Access Journals (Sweden)

    Enders K O Ng

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

  13. Targeting multiple cannabinoid anti-tumour pathways with a resorcinol derivative leads to inhibition of advanced stages of breast cancer.

    Science.gov (United States)

    Murase, Ryuichi; Kawamura, Rumi; Singer, Eric; Pakdel, Arash; Sarma, Pranamee; Judkins, Jonathon; Elwakeel, Eiman; Dayal, Sonali; Martinez-Martinez, Esther; Amere, Mukkanti; Gujjar, Ramesh; Mahadevan, Anu; Desprez, Pierre-Yves; McAllister, Sean D

    2014-10-01

    The psychoactive cannabinoid Δ(9) -tetrahydrocannabinol (THC) and the non-psychoactive cannabinoid cannabidiol (CBD) can both reduce cancer progression, each through distinct anti-tumour pathways. Our goal was to discover a compound that could efficiently target both cannabinoid anti-tumour pathways. To measure breast cancer cell proliferation/viability and invasion, MTT and Boyden chamber assays were used. Modulation of reactive oxygen species (ROS) and apoptosis was measured using dichlorodihydrofluorescein and annexin/propidium iodide, respectively, in combination with cell flow cytometry. Changes in protein levels were evaluated using Western analysis. Orthotopic and i.v. mouse models of breast cancer metastasis were used to test the activity of cannabinoids in vivo. CBD reduced breast cancer metastasis in advanced stages of the disease as the direct result of down-regulating the transcriptional regulator Id1. However, this was associated with moderate increases in survival. We therefore screened for analogues that could co-target cannabinoid anti-tumour pathways (CBD- and THC-associated) and discovered the compound O-1663. This analogue inhibited Id1, produced a marked stimulation of ROS, up-regulated autophagy and induced apoptosis. Of all the compounds tested, it was the most potent at inhibiting breast cancer cell proliferation and invasion in culture and metastasis in vivo. O-1663 prolonged survival in advanced stages of breast cancer metastasis. Developing compounds that can simultaneously target multiple cannabinoid anti-tumour pathways efficiently may provide a novel approach for the treatment of patients with metastatic breast cancer. © 2014 The British Pharmacological Society.

  14. Impact of Preexisting Mental Illness on All-Cause and Breast Cancer-Specific Mortality in Elderly Patients With Breast Cancer.

    Science.gov (United States)

    Iglay, Kristy; Santorelli, Melissa L; Hirshfield, Kim M; Williams, Jill M; Rhoads, George G; Lin, Yong; Demissie, Kitaw

    2017-12-20

    Purpose Limited data are available on the survival of patients with breast cancer with preexisting mental illness, and elderly women are of special interest because they experience the highest incidence of breast cancer. Therefore, we compared all-cause and breast cancer-specific mortality for elderly patients with breast cancer with and without mental illness. Methods A retrospective cohort study was conducted by using SEER-Medicare data, including 19,028 women ≥ 68 years of age who were diagnosed with stage I to IIIa breast cancer in the United States from 2005 to 2007. Patients were classified as having severe mental illness if an International Classification of Diseases, Ninth Edition, Clinical Modification code for bipolar disorder, schizophrenia, or other psychotic disorder was recorded on at least one inpatient or two outpatient claims during the 3 years before breast cancer diagnosis. Patients were followed for up to 5 years after breast cancer diagnosis to assess survival outcomes, which were then compared with those of patients without mental illness. Results Nearly 3% of patients had preexisting severe mental illness. We observed a two-fold increase in the all-cause mortality hazard between patients with severe mental illness compared with those without mental illness after adjusting for age, income, race, ethnicity, geographic location, and marital status (adjusted hazard ratio, 2.19; 95% CI, 1.84 to 2.60). A 20% increase in breast cancer-specific mortality hazard was observed, but the association was not significant (adjusted hazard ratio, 1.20; 95% CI, 0.82 to 1.74). Patients with severe mental illness were more likely to be diagnosed with advanced breast cancer and aggressive tumor characteristics. They also had increased tobacco use and more comorbidities. Conclusion Patients with severe mental illness may need assistance with coordinating medical services.

  15. Anti-RhoC siRNAs inhibit the proliferation and invasiveness of breast cancer cells via modulating the KAI1, MMP9, and CXCR4 expression

    Directory of Open Access Journals (Sweden)

    Xu X

    2017-03-01

    Full Text Available Xu-Dong Xu,1 Han-Bin Shen,1 Li Zhu,2 Jian-Qin Lu,2 Lin Zhang,3 Zhi-Yong Luo,3 Ya-Qun Wu3 1Department of Thyroid and Breast Surgery, The Fifth Hospital of Wuhan, Hanyang District, 2Department of Oncology, 3Department of Thyroid and Breast Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China Abstract: Overexpression of RhoC in breast cancer cells indicates poor prognosis. In the present study, we aim to investigate the possible antitumor effects of anti-RhoC small-interfering RNA (siRNA in inflammatory breast cancer cells. In this study, a specific anti-RhoC siRNA was used to inhibit RhoC synthesis. Transfection of anti-RhoC siRNA into two IBC cells SUM149 and SUM190 induced extensive degradation of target mRNA and led to significant decrease in the synthesis of protein. Anti-RhoC siRNA inhibited cell proliferation and invasion, increased cell apoptosis, and induced cell cycle arrest in vitro. Moreover, the transfection of siRNA increased the expression of KAI1 and decreased the expression of MMP9 and CXCR4 in both mRNA and protein levels. Furthermore, transplantation tumor experiments in BALB/c-nu mice showed that intratumoral injection of anti-RhoC siRNA inhibited tumor growth and increased survival rate. Our results suggested that RhoC gene silencing with specific anti-RhoC siRNA would be a potential therapeutic method for metastatic breast cancer. Keywords: gene silencing, proliferation, apoptosis, cell cycle arrest

  16. Association between frequent use of nonsteroidal anti-inflammatory drugs and breast cancer

    Directory of Open Access Journals (Sweden)

    Rajan Raghu

    2005-12-01

    Full Text Available Abstract Background Eighty percent of all breast cancers and almost 90% of breast cancer deaths occur among post-menopausal women. We used a nested case control design to examine the association between nonsteroidal anti-inflammatory drug (NSAID use and breast cancer occurrence among women over 65 years of age. The cyclooxygenase (COX-2 enzyme is expressed more in breast cancers than in normal breast tissue. COX-2 inhibition may have a role in breast cancer prevention. Methods In the Canadian province of Quebec, physician services are covered through a governmental insurance plan. Medication costs are covered for those ≥ 65 years of age and a publicly funded screening program for breast cancer targets all women 50 years of age or older. We obtained encrypted data from these insurance databases on all women ≥ 65 years of age who filled a prescription for COX-2 inhibitors, non-selective NSAIDs (ns-NSAIDs, aspirin, or acetaminophen between January 1998 and December 2002. Cases were defined as those women who have undergone mammography between April 2001 and June 2002 and had a diagnosis of breast cancer within six months following mammography. Controls included those who have undergone mammography between April 2001 and June 2002 without a diagnosis of any cancer during the six months following mammography. The exposure of interest, frequent NSAID use, was defined as use of ns-NSAIDs and/or COX-2 inhibitors for ≥ 90 days during the year prior to mammography. Frequent use served as a convenient proxy for long term chronic use. Results We identified 1,090 cases and 44,990 controls. Cases were older and more likely to have breast cancer risk factors. Logistic regression models adjusting for potential confounders showed that frequent use of ns-NSAIDs and/or COX-2 inhibitors was associated with a lower risk of breast cancer (OR: 0.75, 95% confidence interval 0.64–0.89. Results were similar for COX-2 inhibitors (0.81, 0.68–0.97 and ns-NSAIDs (0

  17. Low-dose aspirin, non-steroidal anti-inflammatory drugs, selective COX-2 inhibitors and breast cancer recurrence

    DEFF Research Database (Denmark)

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

    2016-01-01

    BACKGROUND: Aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), and selective COX-2 inhibitors may improve outcomes in breast cancer patients. We investigated the association of aspirin, NSAIDs, and use of selective COX-2 inhibitors with breast cancer recurrence. METHODS: We identified incident...... stage I-III Danish breast cancer patients in the Danish Breast Cancer Cooperative Group registry, who were diagnosed during 1996-2008. Prescriptions for aspirin (>99% low-dose aspirin), NSAIDs, and selective COX-2 inhibitors were ascertained from the National Prescription Registry. Follow-up began....... RESULTS: We identified 34,188 breast cancer patients with 233,130 person-years of follow-up. Median follow-up was 7.1 years; 5,325 patients developed recurrent disease. Use of aspirin, NSAIDs, or selective COX-2 inhibitors was not associated with the rate of recurrence (HRadjusted aspirin = 1.0, 95% CI...

  18. Exosomes in development, metastasis and drug resistance of breast cancer.

    Science.gov (United States)

    Yu, Dan-dan; Wu, Ying; Shen, Hong-yu; Lv, Meng-meng; Chen, Wei-xian; Zhang, Xiao-hui; Zhong, Shan-liang; Tang, Jin-hai; Zhao, Jian-hua

    2015-08-01

    Transport through the cell membrane can be divided into active, passive and vesicular types (exosomes). Exosomes are nano-sized vesicles released by a variety of cells. Emerging evidence shows that exosomes play a critical role in cancers. Exosomes mediate communication between stroma and cancer cells through the transfer of nucleic acid and proteins. It is demonstrated that the contents and the quantity of exosomes will change after occurrence of cancers. Over the last decade, growing attention has been paid to the role of exosomes in the development of breast cancer, the most life-threatening cancer in women. Breast cancer could induce salivary glands to secret specific exosomes, which could be used as biomarkers in the diagnosis of early breast cancer. Exosome-delivered nucleic acid and proteins partly facilitate the tumorigenesis, metastasis and resistance of breast cancer. Exosomes could also transmit anti-cancer drugs outside breast cancer cells, therefore leading to drug resistance. However, exosomes are effective tools for transportation of anti-cancer drugs with lower immunogenicity and toxicity. This is a promising way to establish a drug delivery system. © 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

  19. Breast cancer and steroid metabolizing enzymes: the role of progestogens.

    Science.gov (United States)

    Pasqualini, Jorge R

    2009-12-01

    It is well documented that breast tissue, both normal and cancerous, contains all the enzymatic systems necessary for the bioformation and metabolic transformation of estrogens, androgens and progesterone. These include sulfatases, aromatase, hydroxysteroid-dehydrogenases, sulfotransferases, hydroxylases and glucuronidases. The control of these enzymes plays an important role in the development and pathogenesis of hormone-dependent breast cancer. As discussed in this review, various progestogens including dydrogesterone and its 20alpha-dihydro-derivative, medrogestone, promegestone, nomegestrol acetate and norelgestromin can reduce intratissular levels of estradiol in breast cancer by blocking sulfatase and 17beta-hydroxysteroid-dehydrogenase type 1 activities. A possible correlation has been postulated between breast cell proliferation and estrogen sulfotransferase activity. Progesterone is largely transformed in the breast; normal breast produces mainly 4-ene derivatives, whereas 5alpha-derivatives are most common in breast cancer tissue. It has been suggested that this specific conversion of progesterone may be involved in breast carcinogenesis. In conclusion, treatment with anti-aromatases combined with anti-sulfatase or 17beta-hydroxysteroid-dehydrogenase type 1 could provide new therapeutic possibilities in the treatment of patients with hormone-dependent breast cancer. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

  20. Cytotoxicity Enhancement in Breast Cancer Cells with Carbonate Apatite-Facilitated Intracellular Delivery of Anti-Cancer Drugs

    Science.gov (United States)

    Fatemian, Tahereh; Chowdhury, Ezharul Hoque

    2018-01-01

    Pharmacotherapy as the mainstay in the management of breast cancer has demonstrated various drawbacks, including non-targeted bio distribution and narrow therapeutic and safety windows. Thus, enhancements in pharmacodynamic and pharmacokinetic profiles of the classical anti-cancer drugs could lead to improved efficacy against cancer cells. Therefore, inorganic pH-dependent carbonate apatite (CA) nanoparticles were utilized to efficiently deliver various drugs into cancer cells. Following characterization and various modifications in the structure of CA complexes with different drugs, lifted outcomes were achieved. Markedly, complexing paclitaxel with CA resulted in 20.71 ± 4.34% loading efficiency together with 24.14 ± 2.21% enhancement in cytotoxicity on MCF-7 cells plus superior in vivo anti-tumour efficacy compared to free paclitaxel. PMID:29401738

  1. Cytotoxicity Enhancement in Breast Cancer Cells with Carbonate Apatite-Facilitated Intracellular Delivery of Anti-Cancer Drugs

    Directory of Open Access Journals (Sweden)

    Tahereh Fatemian

    2018-02-01

    Full Text Available Pharmacotherapy as the mainstay in the management of breast cancer has demonstrated various drawbacks, including non-targeted bio distribution and narrow therapeutic and safety windows. Thus, enhancements in pharmacodynamic and pharmacokinetic profiles of the classical anti-cancer drugs could lead to improved efficacy against cancer cells. Therefore, inorganic pH-dependent carbonate apatite (CA nanoparticles were utilized to efficiently deliver various drugs into cancer cells. Following characterization and various modifications in the structure of CA complexes with different drugs, lifted outcomes were achieved. Markedly, complexing paclitaxel with CA resulted in 20.71 ± 4.34% loading efficiency together with 24.14 ± 2.21% enhancement in cytotoxicity on MCF-7 cells plus superior in vivo anti-tumour efficacy compared to free paclitaxel.

  2. Occult Breast Cancer: Scintimammography with High-Resolution Breast-specific Gamma Camera in Women at High Risk for Breast Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Rachel F. Brem; Jocelyn A. Rapelyea; , Gilat Zisman; Kevin Mohtashemi; Joyce Raub; Christine B. Teal; Stan Majewski; Benjamin L. Welch

    2005-08-01

    To prospectively evaluate a high-resolution breast-specific gamma camera for depicting occult breast cancer in women at high risk for breast cancer but with normal mammographic and physical examination findings. MATERIALS AND METHODS: Institutional Review Board approval and informed consent were obtained. The study was HIPAA compliant. Ninety-four high-risk women (age range, 36-78 years; mean, 55 years) with normal mammographic (Breast Imaging Reporting and Data System [BI-RADS] 1 or 2) and physical examination findings were evaluated with scintimammography. After injection with 25-30 mCi (925-1110 MBq) of technetium 99m sestamibi, patients were imaged with a high-resolution small-field-of-view breast-specific gamma camera in craniocaudal and mediolateral oblique projections. Scintimammograms were prospectively classified according to focal radiotracer uptake as normal (score of 1), with no focal or diffuse uptake; benign (score of 2), with minimal patchy uptake; probably benign (score of 3), with scattered patchy uptake; probably abnormal (score of 4), with mild focal radiotracer uptake; and abnormal (score of 5), with marked focal radiotracer uptake. Mammographic breast density was categorized according to BI-RADS criteria. Patients with normal scintimammograms (scores of 1, 2, or 3) were followed up for 1 year with an annual mammogram, physical examination, and repeat scintimammography. Patients with abnormal scintimammograms (scores of 4 or 5) underwent ultrasonography (US), and those with focal hypoechoic lesions underwent biopsy. If no lesion was found during US, patients were followed up with scintimammography. Specific pathologic findings were compared with scintimammographic findings. RESULTS: Of 94 women, 78 (83%) had normal scintimammograms (score of 1, 2, or 3) at initial examination and 16 (17%) had abnormal scintimammograms (score of 4 or 5). Fourteen (88%) of the 16 patients had either benign findings at biopsy or no focal abnormality at US; in two

  3. Occult Breast Cancer: Scintimammography with High-Resolution Breast-specific Gamma Camera in Women at High Risk for Breast Cancer

    International Nuclear Information System (INIS)

    Rachel F. Brem; Jocelyn A. Rapelyea; , Gilat Zisman; Kevin Mohtashemi; Joyce Raub; Christine B. Teal; Stan Majewski; Benjamin L. Welch

    2005-01-01

    To prospectively evaluate a high-resolution breast-specific gamma camera for depicting occult breast cancer in women at high risk for breast cancer but with normal mammographic and physical examination findings. MATERIALS AND METHODS: Institutional Review Board approval and informed consent were obtained. The study was HIPAA compliant. Ninety-four high-risk women (age range, 36-78 years; mean, 55 years) with normal mammographic (Breast Imaging Reporting and Data System [BI-RADS] 1 or 2) and physical examination findings were evaluated with scintimammography. After injection with 25-30 mCi (925-1110 MBq) of technetium 99m sestamibi, patients were imaged with a high-resolution small-field-of-view breast-specific gamma camera in craniocaudal and mediolateral oblique projections. Scintimammograms were prospectively classified according to focal radiotracer uptake as normal (score of 1), with no focal or diffuse uptake; benign (score of 2), with minimal patchy uptake; probably benign (score of 3), with scattered patchy uptake; probably abnormal (score of 4), with mild focal radiotracer uptake; and abnormal (score of 5), with marked focal radiotracer uptake. Mammographic breast density was categorized according to BI-RADS criteria. Patients with normal scintimammograms (scores of 1, 2, or 3) were followed up for 1 year with an annual mammogram, physical examination, and repeat scintimammography. Patients with abnormal scintimammograms (scores of 4 or 5) underwent ultrasonography (US), and those with focal hypoechoic lesions underwent biopsy. If no lesion was found during US, patients were followed up with scintimammography. Specific pathologic findings were compared with scintimammographic findings. RESULTS: Of 94 women, 78 (83%) had normal scintimammograms (score of 1, 2, or 3) at initial examination and 16 (17%) had abnormal scintimammograms (score of 4 or 5). Fourteen (88%) of the 16 patients had either benign findings at biopsy or no focal abnormality at US; in two

  4. Targeted nanodiamonds as phenotype-specific photoacoustic contrast agents for breast cancer.

    Science.gov (United States)

    Zhang, Ti; Cui, Huizhong; Fang, Chia-Yi; Cheng, Kun; Yang, Xinmai; Chang, Huan-Cheng; Forrest, M Laird

    2015-03-01

    The aim is to develop irradiated nanodiamonds (INDs) as a molecularly targeted contrast agent for high-resolution and phenotype-specific detection of breast cancer with photoacoustic (PA) imaging. The surface of acid treated radiation-damaged nanodiamonds was grafted with PEG to improve its stability and circulation time in blood, followed by conjugation to an anti-HER2 peptide with a final nanoparticle size of approximately 92 nm. Immunocompetent mice bearing orthotopic HER2-positive or negative tumors were administered INDs and PA imaged using an 820-nm near-infrared laser. PA images demonstrated that INDs accumulate in tumors and completely delineated the entire tumor within 10 h. HER2 targeting significantly enhanced imaging of HER2-positive tumors. Pathological examination demonstrated INDs are nontoxic. PA technology is adaptable to low-cost bedside medicine, and with new contrast agents described herein, PA can achieve high-resolution (sub-mm) and phenotype-specific monitoring of cancer growth.

  5. Nonsteroidal anti-inflammatory drug use and breast cancer risk in a European prospective cohort study

    DEFF Research Database (Denmark)

    Cairat, Manon; Fournier, Agnès; Murphy, Neil

    2018-01-01

    Experimental studies have shown a protective effect of nonsteroidal anti-inflammatory drugs (NSAIDs) on breast cancer development. However, results from epidemiological cohort studies are less consistent. Our objective was to assess the association between NSAID use and breast cancer risk within...... effect modification of MHT use on the association between use of NSAIDs and breast cancer risk which deserves in-depth investigation in studies with accurate data on both NSAID and MHT use. This article is protected by copyright. All rights reserved....... the European Prospective Investigation into Cancer and Nutrition (EPIC). EPIC is a prospective cohort study initiated in 1992 in 10 European countries. Self-reported information on NSAID use at baseline has been collected in five EPIC countries. Multivariable Cox regression models were used to estimate hazard...

  6. Metformin and thiazolidinediones are associated with improved breast cancer-specific survival of diabetic women with HER2+ breast cancer.

    Science.gov (United States)

    He, X; Esteva, F J; Ensor, J; Hortobagyi, G N; Lee, M-H; Yeung, S-C J

    2012-07-01

    Insulin/insulin-like growth factor-I (IGF-I) signaling is a mechanism mediating the promoting effect of type 2 diabetes (DM2) on cancer. Human epidermal growth factor receptor (HER2), insulin receptor and IGF-I receptor involve the same PI3K/AKT/mTOR signaling, and different antidiabetic pharmacotherapy may differentially affect this pathway, leading to different prognoses of HER2+ breast cancer. We reviewed 1983 consecutive patients with HER2+ breast cancer treated between 1 January 1998 and 30 September 2010. The overall survival, breast cancer-specific death rate, age, race, nuclear grade, stage, menopausal status, estrogen and progesterone receptor status, body mass index and classes of antidiabetic pharmacotherapy were analyzed. A Cox regression analysis showed that DM2 [P=0.026, hazard ratio (HR)=1.42, 95 % confidence interval (95 % CI) 1.04-1.94] predicted poor survival of stage≥2 HER2+ breast cancer. In Kaplan-Meier analysis, metformin predicted lengthened survival and so did thiazolidinediones. Analyzing only the diabetics, Cox regression showed that metformin (P=0.041, HR=0.52, 95 % CI 0.28-0.97) and thiazolidinediones (P=0.036; HR=0.41, 95% CI 0.18-0.93) predicted lengthened survival, and competing risk analysis showed that metformin and thiazolidinediones were associated with decreased breast cancer-specific mortality (P=0.023, HR=0.47, 95% CI 0.24-0.90 and P=0.044, HR=0.42, 95 % CI 0.18-0.98, respectively). Thiazolidinediones and metformin users are associated with better clinical outcomes than nonusers in diabetics with stage≥2 HER2+ breast cancer. The choice of antidiabetic pharmacotherapy may influence prognosis of this group.

  7. Usefulness of breast-specific gamma imaging as an adjunct modality in breast cancer patients with dense breast. A comparative study with MRI

    International Nuclear Information System (INIS)

    Kim, Bom Sahn

    2012-01-01

    The aim of this study was to evaluate the adjunctive benefits of breast-specific gamma imaging (BSGI) versus magnetic resonance imaging (MRI) in breast cancer patients with dense breasts. This study included a total of 66 patients (44.1±8.2 years) with dense breasts (breast density >50%) and already biopsy-confirmed breast cancer. All of the patients underwent BSGI and MRI as part of an adjunct modality before the initial therapy. Of 66 patients, the 97 undetermined breast lesions were newly detected and correlated with the biopsy results. Twenty-six of the 97 breast lesions proved to be malignant tumors (invasive ductal cancer, n=16; ductal carcinoma in situ, n=6; mixed or other malignancies, n=4); the remaining 71 lesions were diagnosed as benign tumors. The sensitivity and specificity of BSGI were 88.8% (confidence interval (CI), 69.8-97.6%) and 90.1% (CI, 80.7-95.9%), respectively, while the sensitivity and specificity of MRI were 92.3% (CI, 74.9-99.1%) and 39.4% (CI, 28.0-51.7%), respectively (p<0.0001). MRI detected 43 false-positive breast lesions, 37 (86.0%) of which were correctly diagnosed as benign lesions using BSGI. In 12 malignant lesions <1 cm, the sensitivities of BSGI and MR imaging were 83.3% (CI, 51.6-97.9%) and 91.7% (CI, 61.5-99.8%), respectively. BSGI showed an equivocal sensitivity and a high specificity compared to MRI in the diagnosis of breast lesions. In addition, BSGI had a good sensitivity in discriminating breast cancers ≤1 cm. The results of this study suggest that BSGI could play a crucial role as an adjunctive imaging modality which can be used to evaluate breast cancer patients with dense breasts. (author)

  8. Potential anti-cancer activity of N-hydroxy-7-(2-naphthylthio) heptanomide (HNHA), a histone deacetylase inhibitor, against breast cancer both in vitro and in vivo

    International Nuclear Information System (INIS)

    Park, Ki-Cheong; Kim, Seung-Won; Park, Ji-Hyun

    2011-01-01

    Histone deacetylase (HDAC) is an attractive target for cancer therapy because it plays a key role in gene expression and carcinogenesis. N-hydroxy-7-(2-naphthylthio) heptanomide (HNHA) is a novel synthetic HDAC inhibitor (HDACI) that shows better pharmacological properties than a known HDACI present in the human fibrosarcoma cell: suberoylanilide hydroxamic acid (SAHA). Here, we investigate the anti-cancer activity of HNHA against breast cancer both in vitro and in vivo. HNHA arrested the cell cycle at the G 1 /S phase via p21 induction, which led to profound inhibition of cancer cell growth in vitro. In addition, HNHA-treated cells showed markedly decreased levels of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor (HIF)-1α than SAHA and fumagillin (FUMA) when accompanied by increased histone acetylation. HNHA significantly inhibited tumor growth in an in vivo mouse xenograft model. HNHA-treated mice survived significantly longer than SAHA- and FUMA-treated mice. Dynamic MRI showed significantly decreased blood flow in the HNHA-treated mice, implying that HNHA inhibits tumor neovascularization. This finding was accompanied by marked reductions of proangiogenic factors and significant induction of angiogenesis inhibitors in tumor tissues. We have shown that HNHA is an effective anti-tumor agent in breast cancer cells in vitro and in breast cancer xenografts in vivo. Collectively, these findings indicate that HNHA may be a potent anti-cancer agent against breast cancer due to its multi-faceted inhibition of HDAC activity, as well as anti-angiogenesis activity. (author)

  9. MOLECULAR DOCKING OF COMPOUNDS FROM Chaetomium Sp. AGAINST HUMAN ESTROGEN RECEPTOR ALPHA IN SEARCHING ANTI BREAST CANCER

    Directory of Open Access Journals (Sweden)

    Maywan Hariono

    2016-05-01

    Full Text Available A study on molecular docking-based virtual screening has been conducted to select virtual hit of compounds, reported its existence in fungal endophytes of Chaetomium sp. as cytotoxic agent of breast cancer. The ligands were docked into Human Estrogen Receptor alpha (HERa as the protein which regulates the breast cancer growth via estradiol-estrogen receptor binding intervention. The results showed that two compounds bearing xanthone and two compounds bearing benzonaphtyridinedione scaffolds were selected as virtual hit ligands for HERa leading to the conclusion that these compounds were good to be developed as anti breast cancer.

  10. Antiangiogenic therapy in breast cancer

    OpenAIRE

    Gampenrieder, Simon Peter; Westphal, Theresa; Greil, Richard

    2017-01-01

    Summary Based on a strong rationale for anti-VEGF (vascular endothelial growth factor) treatment in breast cancer and promising preclinical data, great hopes have been placed on the anti-VEGF antibody bevacizumab. Clinical trials, however, reported conflicting results. In metastatic human epidermal growth factor receptor 2(HER2)-negative breast cancer, the addition of bevacizumab to standard chemotherapy improved consistently progression-free survival (PFS), however, without effect on overall...

  11. Specific intracellular signal transduction pathways downstream of CSF-1 receptors: their relationship to breast cancer local recurrence and distant relapse in vivo. Potential targets for the development of new, specific anti-breast cancer therapies to improve local control and block metastatic spread?

    International Nuclear Information System (INIS)

    Kacinski, Barry M.; Sapi, Eva; Flick, Maryann B.; Turner, Bruce; Perrotta, Peter; Maher, M. Grey; Carter, Darryl; Haffy, Bruce

    1997-01-01

    analogues such as Matrigel. Agents which pharmacologically mimic a TYR-721 →PHE mutation by interfering with the activation of elements of intracellular signal transduction downstream of this tyrosine (PI-3 kinase. pp70-S6kinase) produced similar effects. In contrast, a TYR-809→PHE mutation was without effect on anchorage independent growth or the generation of pulmonary metastases but did completely abolish protease production and rendered the transfected cells unable to invade basement membrane analogues. In a parallel line of research, we employed antibodies which recognized CSF-1R and a novel antibody we prepared to recognize CSF-1R only when phosphorylated on TYR-721 in a study of 80 T1 and T2 breast cancer patients treated with tylectomy and primary radiation therapy. Strong staining with the generic anti-CSF-1R antibody correlated strongly with local relapse (P values <.03) in this patient cohort. Staining with the antibody specific for CSF-1R phosphorylated at TYR-721 was not associated with local relapse but did correlate with the development of distant metastases in this cohort of patients, particularly in axillary node-negative patients (P < .006). Conclusion: In summary, our observations demonstrate that CSF-1R activation and phosphorylation at specific tyrosines regulates invasiveness, anchorage, independent growth and tumorigenicity in vitro and in animal models and correlates with metastatic relapse in vivo. They also suggest that such intracellular signaling pathways--particularly those triggered by the phosphorylation of TYR-721 of CSF-1R--are logical targets for the development of a new class of anti-cancer agents which specifically block breast cancer cell metastatic potential without perturbing other normal cellular metabolic processes

  12. Anti-cancer effects of bioactive compounds from rose hip fruit in human breast cancer cell lines

    OpenAIRE

    Zhong, Lijie

    2017-01-01

    Rose hips have long been used in human diets as a food ingredient and supplement. Their multiple medical properties, which have been attributed to their abundant carotenoid composition, have attracted widespread scientific attention. This thesis examined the carotenoid composition in rose hips from five rose species. The anti-cancer effect of different carotenoid fractions from rose hips was investigated in human breast cancer cell lines, using the natural variation in carotenoid content in h...

  13. Production of prostate-specific antigen by a breast cancer cell line, Sk-Br-3

    International Nuclear Information System (INIS)

    Kamali Sarvestani, E.; Ghaderi, A.

    2002-01-01

    Prostate-specific antigen is a 33-KDa serine protease that is produced predominantly by prostate epithelium. However, it has been shown that about 30-40% of female breast tumors produce prostate-specific antigen and its production is associated with the presence of estrogen and progesterone receptors. We have now developed a new tissue culture system to study prostate-specific antigen production in breast cancer and its association with prognostic factors such as progesterone receptor and c-erbB-2. For this purpose we investigated the ability of prostate-specific antigen production in five different cell lines, including two breast cancer cell lines, Sk-Br-3 and MDA-MB-453. The prostate-specific antigen in tissue culture supernatant and cytoplasm of the Sk-Br-3 cell line was detected by western blotting and immunoperoxidase, respectively. Furthermore, we found lower expression of c-erbB-2 in Sk-Br-3 than non-prostate-specific antigen producer breast cancer cell line, MDA-MB-453. Progesterone receptor was expressed by both prostate-specific antigen-positive and -negative cell lines and only the intensity of staining and the number of positive cells in Sk-Br-3 population was higher than MDA-MB-453. According to our findings prostate-specific antigen can be considered as a good prognostic factor in breast cancer and we suggest that these two cell lines are a good in vitro model to study the relationship of different breast cancer prognostic factors and their regulations

  14. Stage-specific predictive models for breast cancer survivability.

    Science.gov (United States)

    Kate, Rohit J; Nadig, Ramya

    2017-01-01

    Survivability rates vary widely among various stages of breast cancer. Although machine learning models built in past to predict breast cancer survivability were given stage as one of the features, they were not trained or evaluated separately for each stage. To investigate whether there are differences in performance of machine learning models trained and evaluated across different stages for predicting breast cancer survivability. Using three different machine learning methods we built models to predict breast cancer survivability separately for each stage and compared them with the traditional joint models built for all the stages. We also evaluated the models separately for each stage and together for all the stages. Our results show that the most suitable model to predict survivability for a specific stage is the model trained for that particular stage. In our experiments, using additional examples of other stages during training did not help, in fact, it made it worse in some cases. The most important features for predicting survivability were also found to be different for different stages. By evaluating the models separately on different stages we found that the performance widely varied across them. We also demonstrate that evaluating predictive models for survivability on all the stages together, as was done in the past, is misleading because it overestimates performance. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  15. Targeted Nanodiamonds as Phenotype Specific Photoacoustic Contrast Agents for Breast Cancer

    Science.gov (United States)

    Zhang, Ti; Cui, Huizhong; Fang, Chia-Yi; Cheng, Kun; Yang, Xinmai; Chang, Huan-Cheng; Forrest, M. Laird

    2015-01-01

    Aim The aim is to develop irradiated nanodiamonds (INDs) as a molecularly-targeted contrast agent for high resolution and phenotype-specific detection of breast cancer with photoacoustic (PA) imaging. Materials & Methods The surface of acid treated radiation-damaged nanodiamonds was grafted with polyethylene glycol (PEG) to improve its stability and circulation time in blood, followed by conjugation to an anti-Human epidermal growth factor receptor-2 (HER2) peptide (KCCYSL) with a final nanoparticle size of ca. 92 nm. Immunocompetent mice bearing orthotopic HER2 positive or negative tumors were administered INDs and PA imaged using an 820-nm near infrared laser. Results PA images demonstrated that INDs accumulate in tumors and completely delineated the entire tumor within 10 hours. HER2 targeting significantly enhanced imaging of HER2-positive tumors. Pathological examination demonstrated INDs are non-toxic. Conclusions PA technology is adaptable to low-cost bedside medicine, and with new contrast agents described herein, PA can achieve high resolution (sub-mm) and phenotype specific monitoring of cancer growth. PMID:25723091

  16. The vitamin E analog, alpha-tocopheryloxyacetic acid enhances the anti-tumor activity of trastuzumab against HER2/neu-expressing breast cancer

    Directory of Open Access Journals (Sweden)

    Penichet Manuel L

    2011-11-01

    Full Text Available Abstract Background HER2/neu is an oncogene that facilitates neoplastic transformation due to its ability to transduce growth signals in a ligand-independent manner, is over-expressed in 20-30% of human breast cancers correlating with aggressive disease and has been successfully targeted with trastuzumab (Herceptin®. Because trastuzumab alone achieves only a 15-30% response rate, it is now commonly combined with conventional chemotherapeutic drugs. While the combination of trastuzumab plus chemotherapy has greatly improved response rates and increased survival, these conventional chemotherapy drugs are frequently associated with gastrointestinal and cardiac toxicity, bone marrow and immune suppression. These drawbacks necessitate the development of new, less toxic drugs that can be combined with trastuzumab. Recently, we reported that orally administered alpha-tocopheryloxyacetic acid (α-TEA, a novel ether derivative of alpha-tocopherol, dramatically suppressed primary tumor growth and reduced the incidence of lung metastases both in a transplanted and a spontaneous mouse model of breast cancer without discernable toxicity. Methods In this study we examined the effect of α-TEA plus HER2/neu-specific antibody treatment on HER2/neu-expressing breast cancer cells in vitro and in a HER2/neu positive human xenograft tumor model in vivo. Results We show in vitro that α-TEA plus anti-HER2/neu antibody has an increased cytotoxic effect against murine mammary tumor cells and human breast cancer cells and that the anti-tumor effect of α-TEA is independent of HER2/neu status. More importantly, in a human breast cancer xenograft model, the combination of α-TEA plus trastuzumab resulted in faster tumor regression and more tumor-free animals than trastuzumab alone. Conclusion Due to the cancer cell selectivity of α-TEA, and because α-TEA kills both HER2/neu positive and HER2/neu negative breast cancer cells, it has the potential to be effective and

  17. Functional genomics identifies specific vulnerabilities in PTEN-deficient breast cancer.

    Science.gov (United States)

    Tang, Yew Chung; Ho, Szu-Chi; Tan, Elisabeth; Ng, Alvin Wei Tian; McPherson, John R; Goh, Germaine Yen Lin; Teh, Bin Tean; Bard, Frederic; Rozen, Steven G

    2018-03-22

    -SSL patterns of activity in a large proportion of PTEN-deficient breast cancer cell lines and are potential specific vulnerabilities in PTEN-deficient breast cancer. Furthermore, the NUAK1 PTEN-SSL vulnerability identified by RNA interference techniques can be recapitulated and exploited using the small molecule kinase inhibitor HTH-01-015. Thus, NUAK1 inhibition may be an effective strategy for precision treatment of PTEN-deficient breast tumors.

  18. S14 as a Therapeutic Target in Breast Cancer

    National Research Council Canada - National Science Library

    Kinlaw, William

    2004-01-01

    .... Our aims are first to develop a model of anti-S14 breast cancer therapy in mice. Intratumoral adenoviral delivery of an S14-antisense gene into human breast cancer cell xenografts caused a significant inhibition of tumor growth...

  19. Breast density and mode of detection in relation to breast cancer specific survival: a cohort study

    International Nuclear Information System (INIS)

    Olsson, Åsa; Sartor, Hanna; Borgquist, Signe; Zackrisson, Sophia; Manjer, Jonas

    2014-01-01

    The aim of this study was to examine breast density in relation to breast cancer specific survival and to assess if this potential association was modified by mode of detection. An additional aim was to study whether the established association between mode of detection and survival is modified by breast density. The study included 619 cases from a prospective cohort, The Malmö Diet and Cancer Study. Breast density estimated qualitatively, was analyzed in relation to breast cancer death, in non-symptomatic and symptomatic women, using Cox regression calculating hazard ratios (HR) with 95% confidence intervals. Adjustments were made in several steps for; diagnostic age, tumour size, axillary lymph node involvement, grade, hormone receptor status, body mass index (baseline), diagnostic period, use of hormone replacement therapy at diagnosis and mode of detection. Detection mode in relation to survival was analyzed stratified for breast density. Differences in HR following different adjustments were analyzed by Freedmans%. After adjustment for age and other prognostic factors, women with dense, as compared to fatty breasts, had an increased risk of breast cancer death, HR 2.56:1.07-6.11, with a statistically significant trend over density categories, p = 0.04. In the stratified analysis, the effect was less pronounced in non-symptomatic women, HR 2.04:0.49-8.49 as compared to symptomatic, HR 3.40:1.06-10.90. In the unadjusted model, symptomatic women had a higher risk of breast cancer death, regardless of breast density. Analyzed by Freedmans%, age, tumour size, lymph nodes, grade, diagnostic period, ER and PgR explained 55.5% of the observed differences in mortality between non-symptomatic and symptomatic cases. Additional adjustment for breast density caused only a minor change. High breast density at diagnosis may be associated with decreased breast cancer survival. This association appears to be stronger in women with symptomatic cancers but breast density could

  20. Robust prediction of anti-cancer drug sensitivity and sensitivity-specific biomarker.

    Directory of Open Access Journals (Sweden)

    Heewon Park

    Full Text Available The personal genomics era has attracted a large amount of attention for anti-cancer therapy by patient-specific analysis. Patient-specific analysis enables discovery of individual genomic characteristics for each patient, and thus we can effectively predict individual genetic risk of disease and perform personalized anti-cancer therapy. Although the existing methods for patient-specific analysis have successfully uncovered crucial biomarkers, their performance takes a sudden turn for the worst in the presence of outliers, since the methods are based on non-robust manners. In practice, clinical and genomic alterations datasets usually contain outliers from various sources (e.g., experiment error, coding error, etc. and the outliers may significantly affect the result of patient-specific analysis. We propose a robust methodology for patient-specific analysis in line with the NetwrokProfiler. In the proposed method, outliers in high dimensional gene expression levels and drug response datasets are simultaneously controlled by robust Mahalanobis distance in robust principal component space. Thus, we can effectively perform for predicting anti-cancer drug sensitivity and identifying sensitivity-specific biomarkers for individual patients. We observe through Monte Carlo simulations that the proposed robust method produces outstanding performances for predicting response variable in the presence of outliers. We also apply the proposed methodology to the Sanger dataset in order to uncover cancer biomarkers and predict anti-cancer drug sensitivity, and show the effectiveness of our method.

  1. Anticancer and Anti-Inflammatory Properties of Ganoderma lucidum Extract Effects on Melanoma and Triple-Negative Breast Cancer Treatment.

    Science.gov (United States)

    Barbieri, Antonio; Quagliariello, Vincenzo; Del Vecchio, Vitale; Falco, Michela; Luciano, Antonio; Amruthraj, Nagoth Joseph; Nasti, Guglielmo; Ottaiano, Alessandro; Berretta, Massimiliano; Iaffaioli, Rosario Vincenzo; Arra, Claudio

    2017-02-28

    Among the most important traditional medicinal fungi, Ganoderma lucidum has been used as a therapeutic agent for the treatment of numerous diseases, including cancer, in Oriental countries. The aim of this study is to investigate the anti-inflammatory, anticancer and anti-metastatic activities of Ganoderma lucidum extracts in melanoma and triple-negative breast cancer cells. Ganoderma lucidum extracts were prepared by using common organic solvents; MDA-MB 231 and B16-F10 cell lines were adopted as cellular models for triple-negative breast cancer and melanoma and characterized for cell viability, wound-healing assay and measurement of cytokines secreted by cancer cells under pro-inflammatory conditions (incubation with lipopolysaccharide, LPS) and pretreatment with Ganoderma lucidum extract at different concentrations. Our study demonstrates, for the first time, how Ganoderma lucidum extracts can significantly inhibit the release of IL-8, IL-6, MMP-2 and MMP-9 in cancer cells under pro-inflammatory condition. Interestingly, Ganoderma lucidum extracts significantly also decrease the viability of both cancer cells in a time- and concentration-dependent manner, with abilities to reduce cell migration over time, which is correlated with a lower release of matrix metalloproteases. Taken together, these results indicate the possible use of Ganoderma lucidum extract for the therapeutic management of melanoma and human triple-negative breast cancer.

  2. Anti-Yo Mediated Paraneoplastic Cerebellar Degeneration Associated with Pseudobulbar Affect in a Patient with Breast Cancer

    Directory of Open Access Journals (Sweden)

    Allison N. Martin

    2017-01-01

    Full Text Available Paraneoplastic cerebellar degeneration (PCD is a rare anti-Yo mediated paraneoplastic syndromes rarely that is infrequently associated with breast cancer. We present a case of a 52-year-old female presenting with diplopia, gait instability, dysarthria, dysphagia, nystagmus, and, most notably, new onset paroxysmal episodes of uncontrollable crying concerning for pseudobulbar affect (PBA. Serologic testing showed anti-Yo antibodies. The patient was found to have stage IIIA breast cancer as the inciting cause of the paraneoplastic syndrome. The patient was treated with neoadjuvant chemotherapy, modified radical mastectomy, adjuvant Herceptin, and pertuzumab. She was given IVIG for paraneoplastic syndrome, antidepressants, and dextromethorphan-quinidine (Nuedexta, the first FDA-approved therapy for PBA. With multimodality therapy, she demonstrated significant improvement in neurologic and mood symptoms associated with PCD and PBA.

  3. PS3-18: Use of Antidepressant and Anti-Anxiety Medications Among Breast Cancer Survivors in a HMO

    Science.gov (United States)

    Avila, Chantal; Haque, Reina; Quinn, Virginia; Schottinger, Joanne; Fisher, Alice

    2010-01-01

    Background: Almost 200,000 U.S. women are diagnosed each year with breast cancer and over 40,000 women will die of the disease. In addition to the medical and functional consequences of the diagnosis and treatment, women experience worry, persistent anxiety, fear and depressive disorders. Overall, 30% of women diagnosed with breast cancer suffer significant distress at some point in their illness trajectory. National health organizations including the Institute of Medicine and National Cancer Institute call for treatment of common symptoms among breast cancer patients such as depression and anxiety. To date, there are only limited reports on the prevalence of treatment, and even fewer studies have examined potential differences by race/ethnicity, age, or tumor characteristics. Aim: To describe the prevalence of pharmacotherapy for depressive symptoms/anxiety among patients diagnosed with breast cancer in a large HMO. Methods: We identified all women diagnosed with primary breast cancer between 2000–2006 (n=10,408) who had been members of Kaiser Permanente Southern California (KPSC) for 1+ years prior to diagnosis. KPSC is a nonprofit comprehensive prepaid health plan serving 3.2 million socioeconomically diverse members. Data was obtained from the KPSC SEER-affiliated cancer registry and automated clinical, pharmacy, and membership databases. We examined patient and tumor characteristics associated with new use of pharmacotherapy for depression/anxiety. Univariate odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression. Results: We found 35% of women (3,611 of 10,408) were newly prescribed either anti-depressant or anti-anxiety medications within a year of breast cancer diagnosis. Younger women (e.g., OR=1.44, CI=1.28–1.63 for 40–49 year olds v. 60–69) and women with higher stage (e.g., OR=3.40, CI=2.87–4.04 for Stage 3 v. Stage 0) were more likely to be prescribed these medications, while African-American (OR=0.81, CI

  4. Evaluation of a high-resolution, breast-specific, small-field-of-view gamma camera for the detection of breast cancer

    International Nuclear Information System (INIS)

    Brem, R.F.; Kieper, D.A.; Rapelyea, J.A.; Majewski, S.

    2003-01-01

    Purpose: The purpose of our study is to review the state of the art in nuclear medicine imaging of the breast (scintimammography) and to evaluate a novel, high-resolution, breast-specific gamma camera (HRBGC) for the detection of suspicious breast lesions. Materials and Methods: Fifty patients with 58 breast lesions in whom a scintimammogram was clinically indicated were prospectively evaluated with a general-purpose gamma camera and a HRBGC prototype. Nuclear studies were prospectively classified as negative (normal/benign) or positive (suspicious/malignant) by two radiologists, blinded to mammographic and histologic results with both the conventional and high-resolution. All lesions were confirmed by pathology. Results: Included in this study were 30 benign and 28 malignant lesions. The sensitivity for detection of breast cancer was 64.3% (18/28) with the conventional camera and 78.6% (22/28) with the HRBGC. Specificity of both systems was 93.3% (28/30). In the 18 nonpalpable cancers, sensitivity was 55.5% (10/18) and 72.2% (13/18) with the general-purpose camera and HRBGC, respectively. In cancers ≤ 1cm, 7 of 15 were detected with the general-purpose camera and 10 of 15 with the HRBGC. Four of the cancers (median size, 8.5 mm) detected with the HRBGC were missed by the conventional camera Conclusion: Evaluation of indeterminate breasts lesions with a high resolution, breast-specific gamma camera results in improved sensitivity for the detection of cancer with greater improvement demonstrated in nonpalpable and ≤1 cm cancers

  5. Oral health-related complications of breast cancer treatment: assessing dental hygienists' knowledge and professional practice.

    Science.gov (United States)

    Taichman, L Susan; Gomez, Grace; Inglehart, Marita Rohr

    2014-04-01

    Approximately 200,000 women are diagnosed with breast cancer in the U.S. every year. These patients commonly suffer from oral complications of their cancer therapy. The purpose of this study was to assess dental hygienists' knowledge and professional practice related to providing care for breast cancer patients. A pre-tested 43-item survey was mailed to a random sample of 10% of all licensed dental hygienists in the state of Michigan (n=962). The survey assessed the respondents' knowledge of potential oral complications of breast cancer treatments as well as their professional practices when treating patients with breast cancer. After 2 mailings, the response rate was 37% (n=331). Descriptive and inferential analyses were conducted using SAS. Many dental hygienists were unaware of the recommended clinical guidelines for treating breast cancer patients and lacked specific knowledge concerning the commonly prescribed anti-estrogen medications for pre-and postmenopausal breast cancer patients. Over 70% of the respondents indicated they were unfamiliar with the AI class of medications. Only 13% of dental hygienists correctly identified the mechanism of action of anti-estrogen therapy. Dental hygienists reported increased gingival inflammation, gingival bleeding, periodontal pocketing, xerostomia and burning tissues in patients receiving anti-estrogen therapies. Less than 10% believed that their knowledge of breast cancer treatments and the potential oral side effects is up to date. Results indicate a need for more education about the oral effects of breast cancer therapies and about providing the best possible care for patients undergoing breast cancer treatment.

  6. Oral Health-Related Complications of Breast Cancer Treatment: Assessing Dental Hygienists’ Knowledge and Professional Practice

    Science.gov (United States)

    Taichman, L. Susan; Gomez, Grace; Inglehart, Marita Rohr

    2017-01-01

    Objective Approximately 200,000 women are diagnosed with breast cancer in the U.S. every year. These patients commonly suffer from oral complications of their cancer therapy. The purpose of this study was to assess dental hygienists’ knowledge and professional practice related to providing care for breast cancer patients. Methods A pre-tested 43-item survey was mailed to a random sample of 10% of all licensed dental hygienists in the State of Michigan (N=962). The survey assessed the respondents’ knowledge of potential oral complications of breast cancer treatments as well as their professional practices when treating patients with breast cancer. After two mailings, the response rate was 37% (N=331). Descriptive and inferential analyses were conducted using SAS. Results Many dental hygienists were unaware of the recommended clinical guidelines for treating breast cancer patients and lacked specific knowledge pertaining to the commonly prescribed anti-estrogen medications for pre-and postmenopausal breast cancer patients. Over 70% of the respondents indicated they were unfamiliar with the AI class of medications. Only 13% of dental hygienists correctly identified the mechanism of action of anti-estrogen therapy. Dental hygienists reported increased gingival inflammation, gingival bleeding, periodontal pocketing, xerostomia and burning tissues in patients receiving anti-estrogen therapies. Less than 10% believed that their knowledge of breast cancer treatments and the oral side effects is up to date. Conclusions Results indicate a need for more education about the potential oral effects of breast cancer therapies and about providing the best possible care for patients undergoing breast cancer treatment. PMID:26338905

  7. Development and Characterization of a Humanized Anti-HER2 Antibody HuA21 with Potent Anti-Tumor Properties in Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Ruilin Li

    2016-04-01

    Full Text Available Human epidermal growth factor receptor 2 (HER2 is one of the most studied tumor-associated antigens for cancer immunotherapy. An engineered anti-HER-2 chimeric A21 antibody (chA21 is a chimeric antibody targeted to subdomain I of the HER2 extracellular domain. Here, we report the anti-tumor activity of the novel engineered monoclonal antibody humanized chA21 (HuA21 that targets HER2 on the basis of chA21, and we describe the underlying mechanisms. Our results reveal that HuA21 markedly inhibits the proliferation and migration of HER2-overexpressing breast cancer cells and causes enhanced antibody-dependent cell-mediated cytotoxicity potency against HER2-overexpressing tumor cells. In particular, HuA21, but not trastuzumab (Tra, markedly suppresses growth and enhances the internalization of the antibody in Tra-resistant BT-474 breast cancer cells. These characteristics are highly associated with the intrinsic ability of HuA21 to down-regulate HER2 activation and inhibit the extracellular signal-regulated kinase 1/2 (ERK1/2 and protein kinase B (Akt signaling pathways. Furthermore, the combination of HuA21 with Tra synergistically enhances the anti-tumor effects in vitro and in vivo and inhibits HER2 activation and the ERK1/2 and Akt signaling pathways. Altogether, our results suggest that HuA21 may represent a unique anti-HER2 antibody with potential as a therapeutic candidate alone or in combination with other anti-HER2 reagents in cancer therapy.

  8. Quantum-Dot-Based Theranostic Micelles Conjugated with an Anti-EGFR Nanobody for Triple-Negative Breast Cancer Therapy.

    Science.gov (United States)

    Wang, Yuyuan; Wang, Yidan; Chen, Guojun; Li, Yitong; Xu, Wei; Gong, Shaoqin

    2017-09-13

    A quantum-dot (QD)-based micelle conjugated with an anti-epidermal growth factor receptor (EGFR) nanobody (Nb) and loaded with an anticancer drug, aminoflavone (AF), has been engineered for EGFR-overexpressing cancer theranostics. The near-infrared (NIR) fluorescence of the indium phosphate core/zinc sulfide shell QDs (InP/ZnS QDs) allowed for in vivo nanoparticle biodistribution studies. The anti-EGFR nanobody 7D12 conjugation improved the cellular uptake and cytotoxicity of the QD-based micelles in EGFR-overexpressing MDA-MB-468 triple-negative breast cancer (TNBC) cells. In comparison with the AF-encapsulated nontargeted (i.e., without Nb conjugation) micelles, the AF-encapsulated Nb-conjugated (i.e., targeted) micelles accumulated in tumors at higher concentrations, leading to more effective tumor regression in an orthotopic triple-negative breast cancer xenograft mouse model. Furthermore, there was no systemic toxicity observed with the treatments. Thus, this QD-based Nb-conjugated micelle may serve as an effective theranostic nanoplatform for EGFR-overexpressing cancers such as TNBCs.

  9. Data of a fluorescent imaging-based analysis of anti-cancer drug effects on three-dimensional cultures of breast cancer cells

    Directory of Open Access Journals (Sweden)

    Junji Itou

    2015-12-01

    Full Text Available Three-dimensional (3D cell culture is a powerful tool to study cell growth under 3D condition. To perform a simple test for anti-cancer drugs in 3D culture, visualization of non-proliferated cells is required. We propose a fluorescent imaging-based assay to analyze cancer cell proliferation in 3D culture. We used a pulse-labeling technique with a photoconvertible fluorescent protein Kaede to identify non-proliferated cells. This assay allows us to observe change in cell proliferation in 3D culture by simple imaging. Using this assay, we obtained the data of the effects of anti-cancer drugs, 5-fluorouracil and PD0332991 in a breast cancer cell line, MCF-7.

  10. Propranolol and survival from breast cancer

    DEFF Research Database (Denmark)

    Cardwell, Chris R; Pottegård, Anton; Vaes, Evelien

    2016-01-01

    BACKGROUND: Preclinical studies have demonstrated that propranolol inhibits several pathways involved in breast cancer progression and metastasis. We investigated whether breast cancer patients who used propranolol, or other non-selective beta-blockers, had reduced breast cancer-specific or all......-cause mortality in eight European cohorts. METHODS: Incident breast cancer patients were identified from eight cancer registries and compiled through the European Cancer Pharmacoepidemiology Network. Propranolol and non-selective beta-blocker use was ascertained for each patient. Breast cancer-specific and all......-analysis techniques. Dose-response analyses by number of prescriptions were also performed. Analyses were repeated investigating propranolol use before cancer diagnosis. RESULTS: The combined study population included 55,252 and 133,251 breast cancer patients in the analysis of breast cancer-specific and all...

  11. Insulin priming effect on estradiol-induced breast cancer metabolism and growth.

    Science.gov (United States)

    Wairagu, Peninah M; Phan, Ai N H; Kim, Min-Kyu; Han, Jeongwoo; Kim, Hyun-Won; Choi, Jong-Whan; Kim, Ki Woo; Cha, Seung-Kuy; Park, Kwang Hwa; Jeong, Yangsik

    2015-01-01

    Diabetes is a risk factor for breast cancer development and is associated with poor prognosis for breast cancer patients. However, the molecular and biochemical mechanisms underlying the association between diabetes and breast cancer have not been fully elucidated. Here, we investigated estradiol response in MCF-7 breast cancer cells with or without chronic exposure to insulin. We found that insulin priming is necessary and specific for estradiol-induced cancer cell growth, and induces anaplerotic shunting of glucose into macromolecule biosynthesis in the estradiol treated cells. Treatment with ERK or Akt specific inhibitors, U0126 or LY294002, respectively, suppressed estradiol-induced growth. Interestingly, molecular analysis revealed that estradiol treatment markedly increases expression of cyclin A and B, and decreases p21 and p27 in the insulin-primed cells. In addition, estradiol treatment activated metabolic genes in pentose phosphate (PPP) and serine biosynthesis pathways in the insulin-primed cells while insulin priming decreased metabolic gene expression associated with glucose catabolism in the breast cancer cells. Finally, we found that anti-diabetic drug metformin and AMPK ligand AICAR, but not thiazolidinediones (TZDs), specifically suppress the estradiol-induced cellular growth in the insulin-primed cells. These findings suggest that estrogen receptor (ER) activation under chronic hyperinsulinemic condition increases breast cancer growth through the modulation of cell cycle and apoptotic factors and nutrient metabolism, and further provide a mechanistic evidence for the clinical benefit of metformin use for ER-positive breast cancer patients with diabetes.

  12. Therapeutic efficacy of MUC1-specific cytotoxic T lymphocytes and CD137 co-stimulation in a spontaneous breast cancer model.

    Science.gov (United States)

    Mukherjee, Pinku; Tinder, Teresa L; Basu, Gargi D; Pathangey, Latha B; Chen, Lieping; Gendler, Sandra J

    2004-01-01

    To study immunology in breast tumors, we have utilized a mammary gland adenocarcinoma model in which mice develop spontaneous tumors of the mammary gland which are initiated at puberty and express a human tumor antigen, MUC1. MUC1 (CD227) is over-expressed in 90% of human breast cancers and its glycosylation status and pattern of expression in cancer cells is altered. Humoral and cellular responses to MUC1 have been reported in breast cancer patients and therefore, MUC1 is being evaluated as a target for immune intervention. This mouse model of spontaneous breast cancer allows the evaluation of anti-MUC1 immune responses at all stages of the disease. In this report, we review the model as it pertains to a) the development of the tumor, b) MUC1 expression, and the native immune responses against MUC1 as tumors progress, and c) the immune suppressive microenvironment within the developing tumor. Finally, we report our latest findings describing the therapeutic efficacy of adoptively transferred MUC1-specific cytotoxic T lymphocytes (MUC1-CTL) in these mice and discuss ways to increase their effectiveness by agonistic monoclonal antibody against CD137 T cell costimulatory molecule.

  13. 2'-Hydroxyflavanone: A novel strategy for targeting breast cancer.

    Science.gov (United States)

    Singhal, Jyotsana; Nagaprashantha, Lokesh; Chikara, Shireen; Awasthi, Sanjay; Horne, David; Singhal, Sharad S

    2017-09-26

    Breast cancer is the most common cancer in women that is driven by cross-talk with hormonal and cellular signaling pathways. The natural phytochemicals, due to broad-spectrum anti-inflammatory and anti-cancerous properties, present with novel opportunities for targeting breast cancer. Intake of citrus fruits is known to reduce the risk for incidence of breast cancer. Hence, we tested the efficacy of citrus flavonoid 2'-hydroxyflavanone (2HF) in breast cancer. 2HF inhibited survival, clonogenic ability, cell cycle progression and induced apoptosis in breast cancer cells. 2HF also decreased VEGF levels and inhibited migratory capacity of breast cancer cells. Administration of 2HF led to regression of triple-negative MDA-MB-231 tumors in the mice xenograft model. 2HF decreased the levels of RLIP76 both in vitro studies and in vivo MDA-MB-231 xenograft model of breast cancer. Western blot and histopathological analyses of resected tumors showed a decline in the levels of survival and proliferation markers Ki67, pAkt, survivin, and cell cycle proteins CDK4 and cyclin B1. 2HF treatment led to inhibition of angiogenesis as determined by decreased VEGF levels in vitro and angiogenesis marker CD31 in vivo . 2HF reversed the pro-/anti-apoptotic ratio of BAX/BCL-2 by decreasing anti-apoptotic protein BCL-2 and increasing pro-apoptotic proteins BAX and BIM in vivo . 2HF also decreased the mesenchymal markers vimentin and fibronectin along with causing a parallel increase in pro-differentiation protein E-cadherin. Collectively, the ability of 2HF to decrease RLIP76, VEGF and regulate critical proliferative, apoptotic and differentiation proteins together provides strong rationale to further develop 2HF based interventions for targeting breast cancer.

  14. 99MTC Alpha-Fetoprotein: A Novel, Specific Agent for the Detection of Human Breast Cancer

    National Research Council Canada - National Science Library

    Line, Bruce

    1998-01-01

    .... We have demonstrated that technetium-99m radiolabeled human alpha-fetoprotein (99mTc AFP) localizes in human breast cancer cells in-vivo, most likely concentrating in breast cancer cells due to a specific receptor not found in normal adult breast tissue...

  15. 99MTC Alpha-Fetoprotein: A Novel, Specific Agent for the Detection of Human Breast Cancer

    National Research Council Canada - National Science Library

    Line, Bruce

    1999-01-01

    .... We have demonstrated that technetium-99m radiolabeled human alpha-fetoprotein (99mTc AFP) localizes in human breast cancer cells in-vivo, most likely concentrating in breast cancer cells due to a specific receptor not found in normal adult breast tissue...

  16. Curcumin in chemoprevention of breast cancer

    Directory of Open Access Journals (Sweden)

    Katarzyna Terlikowska

    2014-01-01

    Full Text Available Breast cancer is the most common malignant cancer among women, both in Poland and worldwide. Due to the constantly increasing number of breast cancer cases, it is vital to develop effective activities in primary and secondary prevention. One of the promising methods of best value, connecting both types of cancer prevention, appears to be chemoprevention. Chemoprevention uses natural or synthetic compounds to inhibit, delay or reverse the process of carcinogenesis. Among ingredients of natural origin, great attention is paid to curcumin – a broad-spectrum anti-cancer polyphenol derivative, extracted from the rhizome of Curcuma longa L. Curcumin has a number of chemopreventive properties such as anti-inflammatory activity, induction of apoptosis, inhibition of angiogenesis as well as tumor metastasis. Numerous in vitro and in vivo studies have demonstrated the mentioned anti-cancer effect in the epithelial breast cell line MCF-10A and in the epithelial breast cell lines MCF-7, BT-474, SK-BR-3-hr and MDA-MB-231. The main problem associated with the use of curcumin as a chemopreventive agent in humans is its low absorption from the gastrointestinal tract, poor solubility in body fluids and low bioavailability. Current studies are underway to increase the bioavailability and effectiveness of curcumin in vivo. Good results in the prevention and the treatment of breast cancer could be ensured by curcumin nanoparticles coated with albumin, known as nanocurcumin. The studies using nanocurcumin, however, are still in the preclinical stage, which is why there is a need to conduct extensive long-term randomized clinical trials to determine its effectiveness.

  17. Cancer-specific self-efficacy and psychosocial and functional adaptation to early stage breast cancer.

    Science.gov (United States)

    Manne, Sharon L; Ostroff, Jamie S; Norton, Tina R; Fox, Kevin; Grana, Generosa; Goldstein, Lori

    2006-04-01

    Although self-efficacy is considered a key psychological resource in adapting to chronic physical illness, this construct has received less attention among individuals coping with cancer. To examine changes in cancer self-efficacy over time among women with early stage breast cancer and associations between task-specific domains of self-efficacy and specific psychological, relationship, and functional outcomes. Ninety-five women diagnosed with early stage breast cancer completed surveys postsurgery and 1 year later. Cancer-related self-efficacy was relatively stable over 1 year, with only 2 domains of efficacy-(a) Activity Management and (b) Self-Satisfaction-evidencing significant increases over the 1-year time period. Cross-sectional findings were relatively consistent with predictions and suggested that specific domains of self-efficacy were more strongly related to relevant domains of adaptation. Longitudinal findings were not as consistent with the domain-specificity hypothesis but did suggest several predictive associations between self-efficacy and outcomes. Personal Management self-efficacy was associated with higher relationship satisfaction, higher Communication Self-Efficacy was associated with less functional impairment, and higher Affective Management self-efficacy was associated with higher self-esteem 1 year later. Specific domains of cancer-related self-efficacy are most closely related to relevant areas of adaptation when considered cross-sectionally, but further study is needed to clarify the nature of these relationships over time.

  18. Autoantibodies in breast cancer sera are not epiphenomena and may participate in carcinogenesis

    International Nuclear Information System (INIS)

    Fernández Madrid, Félix; Maroun, Marie-Claire; Olivero, Ofelia A; Long, Michael; Stark, Azadeh; Grossman, Lawrence I; Binder, Walter; Dong, Jingsheng; Burke, Matthew; Nathanson, S David; Zarbo, Richard; Chitale, Dhananjay; Zeballos-Chávez, Rocío; Peebles, Carol

    2015-01-01

    The objective of this work was to demonstrate that autoantibodies in breast cancer sera are not epiphenomena, and exhibit unique immunologic features resembling the rheumatic autoimmune diseases. We performed a comprehensive study of autoantibodies on a collection of sera from women with breast cancer or benign breast disease, undergoing annual screening mammography. All women in this study had suspicious mammography assessment and underwent a breast biopsy. We used indirect immunofluorescence, the crithidia assay for anti-dsDNA antibodies, and multiple ELISAs for extractable nuclear antigens. Autoantibodies were detected in virtually all patients with breast cancer, predominantly of the IgG1 and IgG3 isotypes. The profile detected in breast cancer sera showed distinctive features, such as antibodies targeting mitochondria, centrosomes, centromeres, nucleoli, cytoskeleton, and multiple nuclear dots. The majority of sera showing anti-mitochondrial antibodies did not react with the M2 component of pyruvate dehydrogenase, characteristic of primary biliary cirrhosis. Anti-centromere antibodies were mainly anti-CENP-B. ELISAs for extractable nuclear antigens and the assays for dsDNA were negative. The distinctive autoantibody profile detected in BC sera is the expression of tumor immunogenicity. Although some of these features resemble those in the rheumatic autoimmune diseases and primary biliary cirrhosis, the data suggest the involvement of an entirely different set of epithelial antigens in breast cancer. High titer autoantibodies targeting centrosomes, centromeres, and mitochondria were detected in a small group of healthy women with suspicious mammography assessment and no cancer by biopsy; this suggests that the process triggering autoantibody formation starts in the pre-malignant phase and that future studies using validated autoantibody panels may allow detection of breast cancer risk in asymptomatic women. Autoantibodies developing in breast cancer are not

  19. Is the skin a sanctuary for breast cancer cells during treatment with anti-HER2 antibodies?

    Science.gov (United States)

    Graziano, Vincenzo; Scognamiglio, Maria Teresa; Zilli, Marinella; Giampietro, Jamara; Vici, Patrizia; Natoli, Clara; Grassadonia, Antonino

    2015-01-01

    The occurrence of skin metastases is a common event in patients affected by advanced breast cancer, usually associated with systemic disease progression. Here we describe 2 cases of diffuse cutaneous metastases from HER2-overexpressing breast cancer occurring despite a dramatic response in liver and bone, respectively, during treatment with anti-HER2 antibodies Trastuzumab and Pertuzumab. We discuss the reasons for this discrepancy and suggest a possible implication of impaired immune response in the skin. Future research should provide strategies to overcome the induction of immune privilege in the skin in order to avoid discontinuation of effective treatments.

  20. The anti-metastatic effects of the phytoestrogen arctigenin on human breast cancer cell lines regardless of the status of ER expression.

    Science.gov (United States)

    Maxwell, Thressi; Chun, So-Young; Lee, Kyu-Shik; Kim, Soyoung; Nam, Kyung-Soo

    2017-02-01

    Arctigenin is a plant lignan extracted from Arctium lappa that has been shown to have estrogenic properties. In spite of the health benefits of phytoestrogens reducing the risk of osteoporosis, heart disease, and menopausal symptoms, its benefits against the risk of breast cancer have not been fully elucidated. Thus, we investigated the effects of arctigenin on metastasis of breast cancer using both estrogen receptor (ER)-positive MCF-7 and ER-negative MDA-MB-231 human breast cancer cell lines to see if the effects are dependent on the status of ER expression. In ER-positive MCF-7 cells, arctigenin efficiently inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced cell migration and invasion. The activity of crucial metastatic protease matrix metalloprotease (MMP)-9 in gelatin zymography was also efficiently decreased by arctigenin, as well as its mRNA expression. Notably, arctigenin exhibited similar anti-metastatic effects even in ER-negative MDA-MB-231 cells, suggesting that the anti-metastatic effects of arctigenin were not exerted via the ER. The upstream signaling pathways involved in the regulation of MMP-9 and urokinase plasminogen activator (uPA) were analyzed using western blotting. The activation of Akt, NF-κB and MAPK (ERK 1/2 and JNK 1/2) was found to be inhibited. Taken together, these data suggest that arctigenin confers anti-metastatic effects by inhibiting MMP-9 and uPA via the Akt, NF-κB and MAPK signaling pathways on breast cancer, regardless of ER expression. Therefore, we propose that the intake of arctigenin could be an effective supplement for breast cancer patients.

  1. Carnosol: a promising anti-cancer and anti-inflammatory agent.

    Science.gov (United States)

    Johnson, Jeremy J

    2011-06-01

    The Mediterranean diet and more specifically certain meats, fruits, vegetables, and olive oil found in certain parts of the Mediterranean region have been associated with a decreased cardiovascular and diabetes risk. More recently, several population based studies have observed with these lifestyle choices have reported an overall reduced risk for several cancers. One study in particular observed an inverse relationship between consumption of Mediterranean herbs such as rosemary, sage, parsley, and oregano with lung cancer. In light of these findings there is a need to explore and identify the anti-cancer properties of these medicinal herbs and to identify the phytochemicals therein. One agent in particular, carnosol, has been evaluated for anti-cancer property in prostate, breast, skin, leukemia, and colon cancer with promising results. These studies have provided evidence that carnosol targets multiple deregulated pathways associated with inflammation and cancer that include nuclear factor kappa B (NFκB), apoptotic related proteins, phosphatidylinositol-3-kinase (PI3 K)/Akt, androgen and estrogen receptors, as well as molecular targets. In addition, carnosol appears to be well tolerated in that it has a selective toxicity towards cancer cells versus non-tumorigenic cells and is well tolerated when administered to animals. This mini-review reports on the pre-clinical studies that have been performed to date with carnosol describing mechanistic, efficacy, and safety/tolerability studies as a cancer chemoprevention and anti-cancer agent. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  2. Homologous recombination deficiency and host anti-tumor immunity in triple-negative breast cancer.

    Science.gov (United States)

    Telli, M L; Stover, D G; Loi, S; Aparicio, S; Carey, L A; Domchek, S M; Newman, L; Sledge, G W; Winer, E P

    2018-05-07

    Triple-negative breast cancer (TNBC) is associated with worse outcomes relative to other breast cancer subtypes. Chemotherapy remains the standard-of-care systemic therapy for patients with localized or metastatic disease, with few biomarkers to guide benefit. We will discuss recent advances in our understanding of two key biological processes in TNBC, homologous recombination (HR) DNA repair deficiency and host anti-tumor immunity, and their intersection. Recent advances in our understanding of homologous recombination (HR) deficiency, including FDA approval of PARP inhibitor olaparib for BRCA1 or BRCA2 mutation carriers, and host anti-tumor immunity in TNBC offer potential for new and biomarker-driven approaches to treat TNBC. Assays interrogating HR DNA repair capacity may guide treatment with agents inducing or targeting DNA damage repair. Tumor infiltrating lymphocytes (TILs) are associated with improved prognosis in TNBC and recent efforts to characterize infiltrating immune cell subsets and activate host anti-tumor immunity offer promise, yet challenges remain particularly in tumors lacking pre-existing immune infiltrates. Advances in these fields provide potential biomarkers to stratify patients with TNBC and guide therapy: induction of DNA damage in HR-deficient tumors and activation of existing or recruitment of host anti-tumor immune cells. Importantly, these advances provide an opportunity to guide use of existing therapies and development of novel therapies for TNBC. Efforts to combine therapies that exploit HR deficiency to enhance the activity of immune-directed therapies offer promise. HR deficiency remains an important biomarker target and potentially effective adjunct to enhance immunogenicity of 'immune cold' TNBCs.

  3. Breast cancer oral anti-cancer medication adherence: a systematic review of psychosocial motivators and barriers.

    Science.gov (United States)

    Lin, Cheryl; Clark, Rachel; Tu, Pikuei; Bosworth, Hayden B; Zullig, Leah L

    2017-09-01

    In the past decade, there has been an increase in the development and use of oral anti-cancer medications (OAMs), especially for breast cancer-the most prevalent cancer in women. However, adherence rates for OAMs are often suboptimal, leading to lower survival rate, increased risk of recurrence, and higher healthcare costs. Our goal was to identify potentially modifiable psychosocial facilitators and barriers that may be targeted to increase OAM adherence for breast cancer patients. We systematically searched PubMed for studies published in the U.S. by June 15, 2016 that addressed the following: (1) OAMs for breast cancer; (2) medication adherence; and (3) at least one psychosocial aspect of adherence. Of the 1752 papers screened, 21 articles were included and analyzed. The most commonly reported motivators for adherence are patient-provider relationships (n = 11 studied, 82% reported significant association) and positive views and beliefs of medication (n = 9 studied, 89% reported significant association). We also identified consistent evidence of the impact of depression and emotions, perception of illness, concern of side effects, self-efficacy in medication management and decision making, knowledge of medication, and social support on OAM adherence. Compared to traditional demographic, system, and clinical-related factors that have been well documented in the literature but are not easily changed, these cognitive, psychological, and interpersonal factors are more amendable via intervention and therefore could generate greater benefit in improving patient compliance and health outcomes. As OAMs shift treatment administration responsibility onto patients, continuous provider communication and education on illness and regimen are the keys to supporting patients' medication behavior.

  4. Phytoestrogen bakuchiol exhibits in vitro and in vivo anti-breast cancer effects by inducing S phase arrest and apoptosis

    Directory of Open Access Journals (Sweden)

    Li eLi

    2016-05-01

    Full Text Available Phytoestrogen has been proposed as an alternative to hormone replacement therapy, which has been demonstrated to promote a high risk of breast cancer. However, the effect of phytoestrogen on breast cancer development has not been fully understood. Bakuchiol is an active ingredient of a traditional Chinese herbal medicine Fructus Psoraleae, the dried ripe fruit of Psoralea corylifolia L. (Fabaceae. The in vitro and in vivo estrogenic activities and anti-breast cancer effects of bakuchiol have not been well studied. We found that bakuchiol induced the GFP expression in transgenic medaka (Oryzias melastigma, Tg, Chg:GFP dose-dependently (0-1 µg/ml, demonstrating its in vivo estrogenic activity. Low dose of bakuchiol (1 µg/ml induced the cell proliferation and ERα expression in MCF-7 cells, which could be blocked by the antiestrogen ICI 182780, suggesting the in vitro estrogenic activity of bakuchiol. Our data indicated that high doses of bakuchiol (>2 µg/ml inhibited breast cancer cell growth, with a stronger antiproliferative effect than resveratrol, a widely studied analogue of bakuchiol. High doses of bakuchiol (4 µg/ml, 7 µg/ml and 10 µg/ml were used for the further in vitro anti-breast cancer studies. Bakuchiol induced ERβ expression and suppressed ERα expression in MCF-7 cells. It also induced S phase arrest in both MCF-7 and MDA-MB-231 cells, which could be rescued by caffeine. Knock-down of p21 also marginally rescued S phase arrest in MCF-7 cells. The S phase arrest was accompanied by the upregulation of ATM, P-Cdc2 (Tyr15, Myt1, P-Wee1 (Ser642, p21 and Cyclin B1, suggesting that blocking of Cdc2 activation may play an important role in bakuchiol-induced S phase arrest. Furthermore, bakuchiol induced cell apoptosis and disturbed mitochondrial membrane potential in MCF-7 cells. The bakuchiol-induced apoptosis was associated with increased expression of Caspase family and Bcl-2 family proteins, suggesting that bakuchiol may induce

  5. Breast and gastrointestinal cancer updates from ASCO 2015.

    Science.gov (United States)

    Dawood, Shaheenah

    2015-01-01

    This review focuses on the updates presented at the ASCO 2015 symposium in breast and gastrointestinal malignancies. Some were practice changing while others gave us an exciting glimpse into what's to come in the very near future. Immunotherapy was the buzz word this year with data presented on every tumor site. Data on the efficacy of anti PD-1 agents in colorectal, hepatocellular and gastric cancer were presented. In breast cancer we saw data on a new and exciting therapeutic target in the form of androgen receptor among triple receptor negative breast tumors presented. Positive results of the PALOMA 3 trial were presented that has given women with hormone receptor positive metastatic breast cancer another therapeutic option. Furthermore data on strategies to further improve anti her2 therapy, optimizing of chemotherapy in the early and advanced stage and various strategies to improve endocrine therapy among patients with breast cancer were presented.

  6. Evaluation of monoclonal antibodies for the development of breast cancer immunotoxins

    International Nuclear Information System (INIS)

    Bjorn, M.J.; Ring, D.; Frankel, A.

    1985-01-01

    Eighty-five antibodies recognizing breast cancer-selective antigens were conjugated to ricin toxin A-chain using a disulfide linkage. The cytotoxicities of the resulting immunotoxins were determined on breast cancer cells and normal human fibroblasts. Twenty-four antibodies formed immunotoxins that were toxic to at least one breast cancer cell line at concentrations of 10 nM or less but were nontoxic to human fibroblast lines used as negative controls. Some of the breast tumor-selective immunotoxins were as toxic as a conjugate between monoclonal anti-transferrin receptor and ricin toxin A-chain (50% inhibition of cellular protein synthesis at approximately 0.1 nM). Another set of four immunotoxins were indiscriminately toxic to human breast tumor cell lines, two human fibroblast cell lines, and a human lymphoblastoid line. Several of the antibodies the toxin conjugates of which specifically killed breast cancer cell lines may be useful in cancer therapy, since they show a wide range of binding to individual breast tumors and cell lines and a limited range of binding to normal tissue types

  7. A targeted proteomics approach to the quantitative analysis of ERK/Bcl-2-mediated anti-apoptosis and multi-drug resistance in breast cancer.

    Science.gov (United States)

    Yang, Ting; Xu, Feifei; Sheng, Yuan; Zhang, Wen; Chen, Yun

    2016-10-01

    Apoptosis suppression caused by overexpression of anti-apoptotic proteins is a central factor to the acquisition of multi-drug resistance (MDR) in breast cancer. As a highly conserved anti-apoptotic protein, Bcl-2 can initiate an anti-apoptosis response via an ERK1/2-mediated pathway. However, the details therein are still far from completely understood and a quantitative description of the associated proteins in the biological context may provide more insights into this process. Following our previous attempts in the quantitative analysis of MDR mechanisms, liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based targeted proteomics was continually employed here to describe ERK/Bcl-2-mediated anti-apoptosis. A targeted proteomics assay was developed and validated first for the simultaneous quantification of ERK1/2 and Bcl-2. In particular, ERK isoforms (i.e., ERK1 and ERK2) and their differential phosphorylated forms including isobaric ones were distinguished. Using this assay, differential protein levels and site-specific phosphorylation stoichiometry were observed in parental drug-sensitive MCF-7/WT cancer cells and drug-resistant MCF-7/ADR cancer cells and breast tissue samples from two groups of patients who were either suspected or diagnosed to have drug resistance. In addition, quantitative analysis of the time course of both ERK1/2 and Bcl-2 in doxorubicin (DOX)-treated MCF-7/WT cells confirmed these findings. Overall, we propose that targeted proteomics can be used generally to resolve more complex cellular events.

  8. Age- and Tumor Subtype-Specific Breast Cancer Risk Estimates for CHEK2*1100delC Carriers

    DEFF Research Database (Denmark)

    Schmidt, Marjanka K; Hogervorst, Frans; van Hien, Richard R

    2016-01-01

    PURPOSE: CHEK2*1100delC is a well-established breast cancer risk variant that is most prevalent in European populations; however, there are limited data on risk of breast cancer by age and tumor subtype, which limits its usefulness in breast cancer risk prediction. We aimed to generate tumor...... subtype- and age-specific risk estimates by using data from the Breast Cancer Association Consortium, including 44,777 patients with breast cancer and 42,997 controls from 33 studies genotyped for CHEK2*1100delC. PATIENTS AND METHODS: CHEK2*1100delC genotyping was mostly done by a custom Taqman assay....... Breast cancer odds ratios (ORs) for CHEK2*1100delC carriers versus noncarriers were estimated by using logistic regression and adjusted for study (categorical) and age. Main analyses included patients with invasive breast cancer from population- and hospital-based studies. RESULTS: Proportions...

  9. Influence of family history, irradiation and anti-cancer drug (mitomycin C) on the occurrence of multiple primary neoplasms in breast carcinoma patients

    International Nuclear Information System (INIS)

    Yoshimoto, Masataka; Sakamoto, Goi; Sugano, Haruo; Kasumi, Fujio; Fukami, Atsuo; Kuno, Keijiro.

    1984-01-01

    The influence of family history, irradiation and anti-cancer drug (Mitomycin C) on the occurrence of multiple primary neoplasms was analysed using the person-year method in 1359 Japanese breast carcinoma patients. There were 111 multiple primary neoplasms, including bilaterl breast cancer, in 109 patients; the incidence rate was 0.0072 per person-year. The incidence rate in patients with a family history of cancer was 1.29 times higher than in those without. In the bilateral breast cancer group there was about a 3 times higher frequency of family history of breast cancer. Irradiation therapy raised the occurrence of multiple primary neoplasms 1.28 fold, and Mitomycin C (40 mg) had no effect on the occurrence of neoplasms during a 10-year observation period. (author)

  10. Survival benefit of anti-HER2 therapy after whole-brain radiotherapy in HER2-positive breast cancer patients with brain metastasis.

    Science.gov (United States)

    Zhang, Qian; Chen, Jian; Yu, Xiaoli; Cai, Gang; Yang, Zhaozhi; Cao, Lu; Hu, Chaosu; Guo, Xiaomao; Sun, Jing; Chen, Jiayi

    2016-09-01

    We aimed to assess the survival benefit of epidermal growth factor receptor 2 (HER2)-positive breast cancer patients with brain metastasis (BM) after whole-brain radiotherapy (WBRT) in combination with systemic treatments, especially anti-HER2 therapy. This retrospective study analyzed the overall survival (OS) of 60 HER2-positive breast cancer patients with BM after WBRT in combination with systemic treatments. Among them, 42 patients received chemotherapy while 18 patients did not receive after WBRT. With regard to anti-HER2 therapy, after WBRT, 17 patients received anti-HER2 treatment without prior adjuvant trastuzumab-based therapy, 7 patients received anti-HER2 treatment with prior adjuvant trastuzumab-based therapy, and 36 patients did not receive further anti-HER2 treatment. All patients were followed up regularly until January 23, 2013. The median OS of patients with BM was 12 months. Patients who received anti-HER2 therapy and chemotherapy after WBRT had significantly better survival compared with patients who did not receive further treatment. Patients who received anti-HER2 treatment after WBRT but did not receive adjuvant trastuzumab-based therapy for early breast cancer had better OS, followed by patients who received anti-HER2 agent both in adjuvant treatment and after WBRT and patients who did not receive anti-HER2 treatment. Multivariate analysis showed that Karnofsky Performance Status, control of extracranial metastases, chemotherapy after WBRT, and anti-HER2 therapy combined with WBRT were all independent predictors for OS. Both chemotherapy and anti-HER2 therapy after WBRT could improve OS. Moreover, patients without prior exposure to adjuvant anti-HER2 treatment may have survival benefit superior to those of patients with prior exposure.

  11. The influence of acculturation and breast cancer-specific distress on perceived barriers to genetic testing for breast cancer among women of African descent.

    Science.gov (United States)

    Sussner, Katarina M; Thompson, Hayley S; Jandorf, Lina; Edwards, Tiffany A; Forman, Andrea; Brown, Karen; Kapil-Pair, Nidhi; Bovbjerg, Dana H; Schwartz, Marc D; Valdimarsdottir, Heiddis B

    2009-09-01

    Rising health disparities are increasingly evident in relation to use of genetic services (including genetic counseling and testing) for breast cancer risk, with women of African descent less likely to use genetic services compared with Whites. Meanwhile, little is known regarding potential within-group acculturation and psychological differences underlying perceived barriers to genetic testing among women of African descent. Hypothesized contributions of acculturation factors and breast cancer-specific distress to perceived barriers to genetic testing were examined with a statistical analysis of baseline data from 146 women of African descent (56% US born and 44% foreign born) meeting genetic breast cancer risk criteria and participating in a larger longitudinal study that included the opportunity for free genetic counseling and testing. Perceived barriers assessed included: (1) anticipation of negative emotional reactions, (2) stigma, (3) confidentiality concerns, (4) family-related worry, and (5) family-related guilt associated with genetic testing. In multivariate analyses, being foreign born was a significant predictor of anticipated negative emotional reactions about genetic testing (beta=0.26; SE=0.11; p=0.01). Breast cancer-specific distress scores (avoidance symptoms) were positively related to anticipated negative emotional reactions (beta=0.02; SE=0.005; p=barriers to genetic testing among women of African descent. The potential utility of culturally tailored genetic counseling services taking into account such influences and addressing emotional and psychological concerns of women considering genetic testing for breast cancer should be investigated.

  12. Reduced expression of α-L-Fucosidase-1 (FUCA-1) predicts recurrence and shorter cancer specific survival in luminal B LN+ breast cancer patients.

    Science.gov (United States)

    Bonin, Serena; Parascandolo, Alessia; Aversa, Cinzia; Barbazza, Renzo; Tsuchida, Nobuo; Castellone, Maria Domenica; Stanta, Giorgio; Vecchio, Giancarlo

    2018-03-16

    The lysosomal enzyme α-L-Fucosidase-1 (FUCA-1) catalyzes the hydrolytic cleavage of terminal fucose residues. FUCA-1 gene is down-regulated in highly aggressive and metastatic human tumors as its inactivation perturbs the fucosylation of proteins involved in cell adhesion, migration and metastases. Negativity to FUCA-1 was significantly related to the development of later recurrences in breast cancer patients with lymph node involvement at diagnosis. Cancer specific survival of luminal B LN+ patients was influenced by FUCA-1 expression as luminal B LN+ patients with positive expression had a longer cancer specific survival. FUCA-1 mRNA expression was inversely related to cancer stage and lymph node involvement. WB and qPCR analysis of FUCA-1 expression in breast cancer-derived cell lines confirmed an inverse relationship with tumor aggressiveness. This study shows that, within LN+ breast cancer patients, FUCA-1 is able to identify a sub-set of non recurrent patients characterized by the positive expression of FUCA-1 and that, within luminal B LN+ patients, the expression of FUCA-1 predicts longer cancer specific survival. We have analyzed FUCA-1 in 305 breast cancer patients by Immunohistochemistry (IHC), and by qPCR in breast cancer patients and in breast cancer cell lines.

  13. Observed and Predicted Risk of Breast Cancer Death in Randomized Trials on Breast Cancer Screening.

    Science.gov (United States)

    Autier, Philippe; Boniol, Mathieu; Smans, Michel; Sullivan, Richard; Boyle, Peter

    2016-01-01

    The role of breast screening in breast cancer mortality declines is debated. Screening impacts cancer mortality through decreasing the number of advanced cancers with poor diagnosis, while cancer treatment works through decreasing the case-fatality rate. Hence, reductions in cancer death rates thanks to screening should directly reflect reductions in advanced cancer rates. We verified whether in breast screening trials, the observed reductions in the risk of breast cancer death could be predicted from reductions of advanced breast cancer rates. The Greater New York Health Insurance Plan trial (HIP) is the only breast screening trial that reported stage-specific cancer fatality for the screening and for the control group separately. The Swedish Two-County trial (TCT)) reported size-specific fatalities for cancer patients in both screening and control groups. We computed predicted numbers of breast cancer deaths, from which we calculated predicted relative risks (RR) and (95% confidence intervals). The Age trial in England performed its own calculations of predicted relative risk. The observed and predicted RR of breast cancer death were 0.72 (0.56-0.94) and 0.98 (0.77-1.24) in the HIP trial, and 0.79 (0.78-1.01) and 0.90 (0.80-1.01) in the Age trial. In the TCT, the observed RR was 0.73 (0.62-0.87), while the predicted RR was 0.89 (0.75-1.05) if overdiagnosis was assumed to be negligible and 0.83 (0.70-0.97) if extra cancers were excluded. In breast screening trials, factors other than screening have contributed to reductions in the risk of breast cancer death most probably by reducing the fatality of advanced cancers in screening groups. These factors were the better management of breast cancer patients and the underreporting of breast cancer as the underlying cause of death. Breast screening trials should publish stage-specific fatalities observed in each group.

  14. Hierarchical clustering of breast cancer methylomes revealed differentially methylated and expressed breast cancer genes.

    Directory of Open Access Journals (Sweden)

    I-Hsuan Lin

    Full Text Available Oncogenic transformation of normal cells often involves epigenetic alterations, including histone modification and DNA methylation. We conducted whole-genome bisulfite sequencing to determine the DNA methylomes of normal breast, fibroadenoma, invasive ductal carcinomas and MCF7. The emergence, disappearance, expansion and contraction of kilobase-sized hypomethylated regions (HMRs and the hypomethylation of the megabase-sized partially methylated domains (PMDs are the major forms of methylation changes observed in breast tumor samples. Hierarchical clustering of HMR revealed tumor-specific hypermethylated clusters and differential methylated enhancers specific to normal or breast cancer cell lines. Joint analysis of gene expression and DNA methylation data of normal breast and breast cancer cells identified differentially methylated and expressed genes associated with breast and/or ovarian cancers in cancer-specific HMR clusters. Furthermore, aberrant patterns of X-chromosome inactivation (XCI was found in breast cancer cell lines as well as breast tumor samples in the TCGA BRCA (breast invasive carcinoma dataset. They were characterized with differentially hypermethylated XIST promoter, reduced expression of XIST, and over-expression of hypomethylated X-linked genes. High expressions of these genes were significantly associated with lower survival rates in breast cancer patients. Comprehensive analysis of the normal and breast tumor methylomes suggests selective targeting of DNA methylation changes during breast cancer progression. The weak causal relationship between DNA methylation and gene expression observed in this study is evident of more complex role of DNA methylation in the regulation of gene expression in human epigenetics that deserves further investigation.

  15. The association between socioeconomic factors and breast cancer-specific survival varies by race.

    Directory of Open Access Journals (Sweden)

    Shailesh Agarwal

    Full Text Available Although racial disparity is well described for oncologic outcomes, factors associated with survival within racial groups remains unexplored. The objective of this study is to determine whether breast cancer survival among White or Black patients is associated with differing patient factors. Women diagnosed with breast cancer from 1998 through 2012 were identified in the Surveillance, Epidemiology, and End Results (SEER database. Cox proportional hazard logistic regression was used to estimate cause-specific survival in the combined cohort, and separate cohorts of Black or White patients only. Main outcomes included cause-specific survival in cohorts of Black only, White only, or all patients adjusted for demographic and oncologic factors. A total of 406,907 Black (10.8% or White (89.2% patients diagnosed with breast cancer from 1998 through 2012 were isolated. Cancer-specific survival analysis of the combined cohort showed significantly decreased hazard ratio (H.R. in patients from the higher economic quartiles (Q1: 1.0 (ref, Q2: 0.95 (p<0.01, Q3: 0.94 (p<0.01, Q4: 0.87 (p<0.001. Analysis of the White only cohort showed a similar relationship with income (Q1: 1.0 (ref, Q2: 0.95 (p<0.01, Q3: 0.95 (p<0.01, Q4: 0.86 (p<0.001. However, analysis of the Black only cohort did not show a relationship with income (Q1: 1.0 (ref, Q2: 1.04 (p = 0.34, Q3: 0.97 (p = 0.53, Q4: 1.04 (p = 0.47. A test of interaction confirmed that the association between income and cancer-specific survival is dependent on patient race, both with and without adjustment for demographic and oncologic characteristics (p<0.01. While median county income is positively associated with cancer-specific survival among White patients, this is not the case with Black patients. Similar findings were noted for education level. These findings suggest that the association between socioeconomic status and breast cancer survival commonly reported in the literature is specific to White patients

  16. Targeted Therapy for Breast Cancer Prevention

    Science.gov (United States)

    den Hollander, Petra; Savage, Michelle I.; Brown, Powel H.

    2013-01-01

    With a better understanding of the etiology of breast cancer, molecularly targeted drugs have been developed and are being testing for the treatment and prevention of breast cancer. Targeted drugs that inhibit the estrogen receptor (ER) or estrogen-activated pathways include the selective ER modulators (tamoxifen, raloxifene, and lasofoxifene) and aromatase inhibitors (AIs) (anastrozole, letrozole, and exemestane) have been tested in preclinical and clinical studies. Tamoxifen and raloxifene have been shown to reduce the risk of breast cancer and promising results of AIs in breast cancer trials, suggest that AIs might be even more effective in the prevention of ER-positive breast cancer. However, these agents only prevent ER-positive breast cancer. Therefore, current research is focused on identifying preventive therapies for other forms of breast cancer such as human epidermal growth factor receptor 2 (HER2)-positive and triple-negative breast cancer (TNBC, breast cancer that does express ER, progesterone receptor, or HER2). HER2-positive breast cancers are currently treated with anti-HER2 therapies including trastuzumab and lapatinib, and preclinical and clinical studies are now being conducted to test these drugs for the prevention of HER2-positive breast cancers. Several promising agents currently being tested in cancer prevention trials for the prevention of TNBC include poly(ADP-ribose) polymerase inhibitors, vitamin D, and rexinoids, both of which activate nuclear hormone receptors (the vitamin D and retinoid X receptors). This review discusses currently used breast cancer preventive drugs, and describes the progress of research striving to identify and develop more effective preventive agents for all forms of breast cancer. PMID:24069582

  17. Walking a Tightrope: A Perspective of Resveratrol Effects on Breast Cancer.

    Science.gov (United States)

    Bartolacci, Caterina; Andreani, Cristina; Amici, Augusto; Marchini, Cristina

    2018-01-01

    It is an acknowledged fact that health benefits are derived from fruit- and vegetables-enriched diets. In particular, polyphenols, compounds bearing one or more hydroxyl groups attached to an aromatic ring, are ascribed for most of such beneficial effects. Among them, resveratrol, a phytoalexin found in numerous plant species, and more notably in grapes, has widely piqued the interest of the scientific community by virtue of its anti-aging, anti-inflammatory and anti-oxidant properties. Moreover, evidence claiming resveratrol ability to hinder processes underlying all the three steps of carcinogenesis (tumor initiation, progression and metastasization) has propelled an incredibly massive number of studies aimed at enquiring its eventual clinical potential in the fight against cancer. However, despite a large body of data pointing to the advantages of dietary resveratrol intake in respect of certain disease conditions, and cancer inter alia, its real position still remains quite ambiguous. In this uncertain scenario, the present review focuses its attention on the highly entangled relationship between resveratrol and breast cancer, attempting to shape the plethora of controversial results stemming from studies carried out on several in vitro and in vivo breast cancer models. Coping with such a tricky matter, there are so many variabilities concerning both resveratrol itself (dosage, administration, bioavailabilty, among others) and the unique molecular traits of each specific breast cancer subtype that must be taken into account when facing the dilemma: "might resveratrol be protective against breast cancer or does it rather fuel it?". Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  18. Anti-cancer Lead Molecule

    KAUST Repository

    Sagar, Sunil; Kaur, Mandeep; Esau, Luke E.

    2014-01-01

    Derivatives of plumbagin can be selectively cytotoxic to breast cancer cells. Derivative `A` (Acetyl Plumbagin) has emerged as a lead molecule for testing against estrogen positive breast cancer and has shown low hepatotoxicity as well as overall lower toxicity in nude mice model. The toxicity of derivative `A` was determined to be even lower than vehicle control (ALT and AST markers). The possible mechanism of action identified based on the microarray experiments and pathway mapping shows that derivative `A` could be acting by altering the cholesterol-related mechanisms. The low toxicity profile of derivative `A` highlights its possible role as future anti-cancer drug and/or as an adjuvant drug to reduce the toxicity of highly toxic chemotherapeutic drugs

  19. Anti-cancer Lead Molecule

    KAUST Repository

    Sagar, Sunil

    2014-04-17

    Derivatives of plumbagin can be selectively cytotoxic to breast cancer cells. Derivative `A` (Acetyl Plumbagin) has emerged as a lead molecule for testing against estrogen positive breast cancer and has shown low hepatotoxicity as well as overall lower toxicity in nude mice model. The toxicity of derivative `A` was determined to be even lower than vehicle control (ALT and AST markers). The possible mechanism of action identified based on the microarray experiments and pathway mapping shows that derivative `A` could be acting by altering the cholesterol-related mechanisms. The low toxicity profile of derivative `A` highlights its possible role as future anti-cancer drug and/or as an adjuvant drug to reduce the toxicity of highly toxic chemotherapeutic drugs

  20. β-Catenin Mediates Anti-adipogenic and Anticancer Effects of Arctigenin in Preadipocytes and Breast Cancer Cells.

    Science.gov (United States)

    Lee, Jihye; Imm, Jee-Young; Lee, Seong-Ho

    2017-03-29

    Arctigenin is a lignan abundant in Asteraceae plants and has anti-inflammatory, antiobesity, and anticancer activities. Obesity is one of the leading causes of several types of cancers including breast cancer. The current study was performed to investigate if arctigenin suppresses differentiation of preadipocytes and proliferation of breast cancer cells and to explore potential molecular mechanisms. Treatment of arctigenin reduced lipid accumulation in differentiated 3T3-L1 adipocytes in a dose- and time-dependent manner without toxicity. Arctigenin suppressed the expression of peroxisome proliferator-activated receptor-gamma (PPARγ), CCAAT/enhancer-binding protein-alpha (C/EBPα), perilipin, and fatty acid binding protein 4 (FABP4) in a dose-dependent manner in differentiated 3T3-L1 cells. Both total and unphosphorylated (active) β-catenin were increased in whole cell lysates and the nuclear fraction of differentiated 3T3-L1 cells treated with 25 μM arctigenin. On the other hand, arctigenin decreased proliferation of two human breast cancer cells (MCF-7 and MDA-MB-231). Arctigenin induced apoptosis and decreased expression of total and unphosphorylated (active) β-catenin and cyclin D1 in MCF-7, but not in MDA-MB-231. These data indicate that arctigenin suppressed adipogenesis in preadipocytes and activated apoptosis in estrogen receptor (ER) positive breast cancer cells through modulating expression of β-catenin.

  1. Female breast cancer in Vietnam: a comparison across Asian specific regions.

    Science.gov (United States)

    Trieu, Phuong Dung Yun; Mello-Thoms, Claudia; Brennan, Patrick C

    2015-09-01

    Breast cancer is one of the most commonly diagnosed malignancies and the leading cause of cancer death of women over the world. A large number of females with breast cancer in Vietnam and other Southeast Asian (SEA) countries present at an early age with more aggressive tumors compared with women in Australia. Despite experiencing a low incidence rate, the increasing incidence rate among SEA countries exceeds that of the Westernized world. Changes in reproductive factors, environmental exposures, and lifestyle are the possible causes of this trend. However, limited evidence shows that these factors are associated with breast cancer in the Vietnamese population. Breast cancer incidence rates within Vietnam are not uniform and appear to be dependent on geographic location. Findings from this review have important implications for breast cancer control and treatment in Vietnam. A good understanding of the morphology of the breast and the type and nature of breast cancers presenting in Vietnam is required to facilitate the introduction of an effective national breast screening program.

  2. Checkpoint inhibitors in breast cancer

    DEFF Research Database (Denmark)

    Polk, Anne; Svane, Inge-Marie; Andersson, Michael

    2018-01-01

    INTRODUCTION: An increasing number of compounds directed against immune checkpoints are currently under clinical development. In this review we summarize current research in breast cancer. MATERIAL AND METHODS: A computer-based literature search was carried out using PubMed and EMBASE; data...... reported at international meetings and clinicaltrials.gov were included as well. RESULTS: The obtained overall response rate of PD-1/PD-L1 monotherapy varied from 5 to 30% in heavily pretreated triple negative breast cancer (TNBC). The median duration of progression free survival and overall survival were...... and induce long standing anti-tumor immunity in a subgroup of breast cancer patients. However, the identification of predictive biomarkers is crucial for further development of this treatment modality....

  3. Dermatomyositis with anti-TIF-1γ antibodies as a presenting symptom of underlying triple-negative breast cancer: a case report

    International Nuclear Information System (INIS)

    Kubeček, Ondřej; Soukup, Tomáš; Paulík, Adam; Kopecký, Jindřich

    2016-01-01

    Dermatomyositis is an autoimmune myopathy characterized by proximal muscle weakness, muscle inflammation, and typical skin findings. It is a rare disease with an incidence of ~1/100 000. About 15–30 % of adult-onset cases are caused by underlying malignancy and dermatomyositis can be the first symptom of undiagnosed cancer, mainly in the case of anti-transcription intermediary factor 1γ (anti-TIF-1γ) antibodies presence. TIF-1γ is a transcriptional cofactor which is implicated in TGFβ signaling pathway that controls cell proliferation, differentiation, apoptosis, and tumorigenesis. Its expression was shown to be associated with younger age, higher tumor grade, more estrogen receptor negativity, tumors larger than 2 cm, and tendency towards poor outcome in early breast cancer. No association between anti-TIF-1γ antibodies and prognosis has been proposed yet. We report a case of a 43-year-old premenopausal woman presenting with the symptoms of systemic rheumatic disease, the most prominent being a typical skin rash and muscle pain. After a series of investigations, the patient was diagnosed with anti-TIF-1γ positive dermatomyositis and concurrent triple-negative breast cancer (cT1c N3c M0) as an underlying cause. Immediate intravenous corticosteroid therapy relieved the symptoms and enabled anticancer therapy to be commenced. Considering the tumor stage, neoadjuvant therapy with 4 courses of AC (Doxorubicin/Cyclophosphamide) followed by 4 courses of Paclitaxel/Carboplatin was administered. However, no tumor regression was documented and radiotherapy was chosen as the definitive treatment. Early detection of anti-TIF-1γ autoantibodies can contribute to a rapid diagnosis of tumor-associated dermatomyositis and enable immediate anticancer treatment. We demonstrate the emerging role of anti-TIF-1γ antibodies in the diagnostics of tumor-associated dermatomyositis. Furthermore, we propose a potential role of anti-TIF-1γ antibodies as a prognostic marker in early

  4. Cordycepin-induced apoptosis and autophagy in breast cancer cells are independent of the estrogen receptor

    International Nuclear Information System (INIS)

    Choi, Sunga; Lim, Mi-Hee; Kim, Ki Mo; Jeon, Byeong Hwa; Song, Won O.; Kim, Tae Woong

    2011-01-01

    Cordycepin (3-deoxyadenosine), found in Cordyceps spp., has been known to have many therapeutic effects including immunomodulatory, anti-inflammatory, antimicrobial, and anti-aging effects. Moreover, anti-tumor and anti-metastatic effects of cordycepin have been reported, but the mechanism causing cancer cell death is poorly characterized. The present study was designed to investigate whether the mechanisms of cordycepin-induced cell death were associated with estrogen receptor in breast cancer cells. Exposure of both MDA-MB-231 and MCF-7 human breast cancer cells to cordycepin resulted in dose-responsive inhibition of cell growth and reduction in cell viability. The cordycepin-induced cell death in MDA-MB-231 cells was associated with several specific features of the mitochondria-mediated apoptotic pathway, which was confirmed by DNA fragmentation, TUNEL, and biochemical assays. Cordycepin also caused a dose-dependent increase in mitochondrial translocation of Bax, triggering cytosolic release of cytochrome c and activation of caspases-9 and -3. Interestingly, MCF-7 cells showed autophagy-associated cell death, as observed by the detection of an autophagosome-specific protein and large membranous vacuole ultrastructure morphology in the cytoplasm. Cordycepin-induced autophagic cell death has applications in treating MCF-7 cells with apoptotic defects, irrespective of the ER response. Although autophagy has a survival function in tumorigenesis of some cancer cells, autophagy may be important for cordycepin-induced MCF-7 cell death. In conclusion, the results of our study demonstrate that cordycepin effectively kills MDA-MB-231 and MCF-7 human breast cancer cell lines in culture. Hence, further studies should be conducted to determine whether cordycepin will be a clinically useful, ER-independent, chemotherapeutic agent for human breast cancer. -- Highlights: ► We studied the mechanism which cordycepin-induced cell death association with estrogen receptor (ER) in

  5. SPECIFIC CHARACTERISTICS OF BRAIN METASTASIZING IN PATIENTS WITH LUMINAL SUBTYPE OF BREAST CANCER

    Directory of Open Access Journals (Sweden)

    A. S. Balkanov

    2016-01-01

    Full Text Available Background: More than half of female patients with breast cancer are diagnosed with a  luminal subtype of the disease; however, specific characteristics of its metastases to the brain have been not well studied, unlike those of HER2 positive and triple negative subtypes. Aim: A  comparative analysis of characteristics of metastatic brain lesions in patients with luminal breast cancer. Materials and methods: The time from surgery for breast cancer to the first recurrence and to metastatic brain lesions (assessed by contrast-enhanced MRI imaging was measured in 41 patients with luminal subtype of breast cancer (median age, 49.5±9.6  years, depending on a  diameter of the primary tumor and numbers of involved axillary lymph nodes. Results: The time interval to occurrence of brain metastases in luminal subtype of breast cancer is not associated with the size of the tumor. If≥4  axillary lymph nodes are involved (N2–3, brain metastases are identified much earlier (p<0.05 than in patients with N0–1 (34.5±23.9 months and 62.7±50 months, respectively. Neither the size nor the involvement of axillary lymph nodes has any impact on the rates of metastatic lesion to the brain during the first recurrence. Conclusion: Brain metastases occur at a much shorter time in those patients of luminal subtype of breast cancer who have metastases in≥4  axillary lymph nodes. Brain metastases develop in 50% of patients with the first recurrence of the luminal subtype of breast cancer.

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

    DEFF Research Database (Denmark)

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

    2016-01-01

    BACKGROUND/AIM: Primary tumors display a great level of intra-tumor heterogeneity in breast cancer. The current lack of prognostic and predictive biomarkers limits accurate stratification and the ability to predict response to therapy. The aim of the present study was to select recombinant antibody...... fragments specific against breast cancer subpopulations, aiding the discovery of novel biomarkers. MATERIALS AND METHODS: Recombinant antibody fragments were selected by phage display. A novel shadowstick technology enabled the direct selection using tissue sections of antibody fragments specific against...

  7. Melatonin and breast cancer: Evidences from preclinical and human studies.

    Science.gov (United States)

    Kubatka, Peter; Zubor, Pavol; Busselberg, Dietrich; Kwon, Taeg Kyu; Adamek, Mariusz; Petrovic, Daniel; Opatrilova, Radka; Gazdikova, Katarina; Caprnda, Martin; Rodrigo, Luis; Danko, Jan; Kruzliak, Peter

    2018-02-01

    The breast cancer affects women with high mortality and morbidity worldwide. The risk is highest in the most developed world but also is markedly rising in the developing countries. It is well documented that melatonin has a significant anti-tumor activities demonstrated on various cancer types in a plethora of preclinical studies. In breast cancer, melatonin is capable to disrupt estrogen-dependent cell signaling, resulting in a reduction of estrogen-stimulated cells, moreover, it's obvious neuro-immunomodulatory effect in organism was described. Several prospective studies have demonstrated the inverse correlation between melatonin metabolites and the risk of breast cancer. This correlation was confirmed by observational studies that found lower melatonin levels in breast cancer patients. Moreover, clinical studies have showed that circadian disruption of melatonin synthesis, specifically night shift work, is linked to increased breast cancer risk. In this regard, proper light/dark exposure with more selective use of light at night along with oral supplementation of melatonin may have benefits for high-risk women. The results of current preclinical studies, the mechanism of action, and clinical efficacy of melatonin in breast cancer are reviewed in this paper. Melatonin alone or in combined administration seems to be appropriate drug for the treatment of early stages of breast cancer with documented low toxicity over a wide range of doses. These and other issues are also discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Subtype and pathway specific responses to anticancer compounds in breast cancer.

    Science.gov (United States)

    Heiser, Laura M; Sadanandam, Anguraj; Kuo, Wen-Lin; Benz, Stephen C; Goldstein, Theodore C; Ng, Sam; Gibb, William J; Wang, Nicholas J; Ziyad, Safiyyah; Tong, Frances; Bayani, Nora; Hu, Zhi; Billig, Jessica I; Dueregger, Andrea; Lewis, Sophia; Jakkula, Lakshmi; Korkola, James E; Durinck, Steffen; Pepin, François; Guan, Yinghui; Purdom, Elizabeth; Neuvial, Pierre; Bengtsson, Henrik; Wood, Kenneth W; Smith, Peter G; Vassilev, Lyubomir T; Hennessy, Bryan T; Greshock, Joel; Bachman, Kurtis E; Hardwicke, Mary Ann; Park, John W; Marton, Laurence J; Wolf, Denise M; Collisson, Eric A; Neve, Richard M; Mills, Gordon B; Speed, Terence P; Feiler, Heidi S; Wooster, Richard F; Haussler, David; Stuart, Joshua M; Gray, Joe W; Spellman, Paul T

    2012-02-21

    Breast cancers are comprised of molecularly distinct subtypes that may respond differently to pathway-targeted therapies now under development. Collections of breast cancer cell lines mirror many of the molecular subtypes and pathways found in tumors, suggesting that treatment of cell lines with candidate therapeutic compounds can guide identification of associations between molecular subtypes, pathways, and drug response. In a test of 77 therapeutic compounds, nearly all drugs showed differential responses across these cell lines, and approximately one third showed subtype-, pathway-, and/or genomic aberration-specific responses. These observations suggest mechanisms of response and resistance and may inform efforts to develop molecular assays that predict clinical response.

  9. The presence of tumor associated macrophages in tumor stroma as a prognostic marker for breast cancer patients

    International Nuclear Information System (INIS)

    Medrek, Catharina; Pontén, Fredrik; Jirström, Karin; Leandersson, Karin

    2012-01-01

    Tumor associated macrophages (TAMs) are alternatively activated macrophages that enhance tumor progression by promoting tumor cell invasion, migration and angiogenesis. TAMs have an anti-inflammatory function resembling M2 macrophages. CD163 is regarded as a highly specific monocyte/macrophage marker for M2 macrophages. In this study we evaluated the specificity of using the M2 macrophage marker CD163 as a TAM marker and compared its prognostic value with the more frequently used pan-macrophage marker CD68. We also analyzed the prognostic value of the localization of CD163 + and CD68 + myeloid cells in human breast cancer. The extent of infiltrating CD163 + or CD68 + myeloid cells in tumor nest versus tumor stroma was evaluated by immunohistochemistry in tissue microarrays with tumors from 144 breast cancer cases. Spearman’s Rho and χ 2 tests were used to examine the correlations between CD163 + or CD68 + myeloid cells and clinicopathological parameters. Kaplan Meier analysis and Cox proportional hazards modeling were used to assess the impact of CD163 + and CD68 + myeloid cells in tumor stroma and tumor nest, respectively, on recurrence free survival, breast cancer specific and overall survival. We found that infiltration of CD163 + and CD68 + macrophages into tumor stroma, but not into tumor nest, were of clinical relevance. CD163 + macrophages in tumor stroma positively correlated with higher grade, larger tumor size, Ki67 positivity, estrogen receptor negativity, progesterone receptor negativity, triple-negative/basal-like breast cancer and inversely correlated with luminal A breast cancer. Some CD163 + areas lacked CD68 expression, suggesting that CD163 could be used as a general anti-inflammatory myeloid marker with prognostic impact. CD68 + macrophages in tumor stroma positively correlated to tumor size and inversely correlated to luminal A breast cancer. More importantly, CD68 in tumor stroma was an independent prognostic factor for reduced breast cancer

  10. Breast MRI in pregnancy-associated breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Shin Jung; Shin, Sang Soo [Dept. of of Radiology, Chonnam National University Hospital, Gwangju (Korea, Republic of); Lim, Hyo Soon; Baek, Jang Mi; Seon, Hyun Ju; Heo, Suk Hee; Kim, Jin Woong; Park, Min Ho [Chonnam National University Medical School, Chonnam National University Hwasun Hospital, Hwasun (Korea, Republic of)

    2017-03-15

    The purpose of this study was to evaluate the usefulness of MR imaging and to describe the MR imaging findings of pregnancy-associated breast cancer. From 2006 to 2013, MR images of 23 patients with pregnancy-associated breast cancer were retrospectively evaluated. MR images were reviewed to evaluate lesion detection and imaging findings of pregnancy-associated breast cancer. MR images were analyzed by using the Breast Imaging Reporting and Data System and an additional MR-detected lesion with no mammographic or sonographic abnormality was determined. MR imaging depicted breast cancer in all patients, even in marked background parenchymal enhancement. Pregnancy-associated breast cancer was seen as a mass in 20 patients and as non-mass enhancement with segmental distribution in 3 patients. The most common features of the masses were irregular shape (85%), non-circumscribed margin (85%), and heterogeneous enhancement (60%). An additional site of cancer was detected with MR imaging in 5 patients (21.7%) and the type of surgery was changed. Pregnancy-associated breast cancer was usually seen as an irregular mass with heterogeneous enhancement on MR images. Although these findings were not specific, MR imaging was useful in evaluating the disease extent of pregnancy-associated breast cancer.

  11. Breast MRI in pregnancy-associated breast cancer

    International Nuclear Information System (INIS)

    Kim, Shin Jung; Shin, Sang Soo; Lim, Hyo Soon; Baek, Jang Mi; Seon, Hyun Ju; Heo, Suk Hee; Kim, Jin Woong; Park, Min Ho

    2017-01-01

    The purpose of this study was to evaluate the usefulness of MR imaging and to describe the MR imaging findings of pregnancy-associated breast cancer. From 2006 to 2013, MR images of 23 patients with pregnancy-associated breast cancer were retrospectively evaluated. MR images were reviewed to evaluate lesion detection and imaging findings of pregnancy-associated breast cancer. MR images were analyzed by using the Breast Imaging Reporting and Data System and an additional MR-detected lesion with no mammographic or sonographic abnormality was determined. MR imaging depicted breast cancer in all patients, even in marked background parenchymal enhancement. Pregnancy-associated breast cancer was seen as a mass in 20 patients and as non-mass enhancement with segmental distribution in 3 patients. The most common features of the masses were irregular shape (85%), non-circumscribed margin (85%), and heterogeneous enhancement (60%). An additional site of cancer was detected with MR imaging in 5 patients (21.7%) and the type of surgery was changed. Pregnancy-associated breast cancer was usually seen as an irregular mass with heterogeneous enhancement on MR images. Although these findings were not specific, MR imaging was useful in evaluating the disease extent of pregnancy-associated breast cancer

  12. Resolving breast cancer heterogeneity by searching reliable protein cancer biomarkers in the breast fluid secretome

    International Nuclear Information System (INIS)

    Mannello, Ferdinando; Ligi, Daniela

    2013-01-01

    One of the major goals in cancer research is to find and evaluate the early presence of biomarkers in human fluids and tissues. To resolve the complex cell heterogeneity of a tumor mass, it will be useful to characterize the intricate biomolecular composition of tumor microenvironment (the so called cancer secretome), validating secreted proteins as early biomarkers of cancer initiation and progression. This approach is not broadly applicable because of the paucity of well validated and FDA-approved biomarkers and because most of the candidate biomarkers are mainly organ-specific rather than tumor-specific. For these reasons, there is an urgent need to identify and validate a panel of biomarker combinations for early detection of human tumors. This is especially important for breast cancer, the cancer spread most worldwide among women. It is well known that patients with early diagnosed breast cancer live longer, require less extensive treatment and fare better than patients with more aggressive and/or advanced disease. In the frame of searching breast cancer biomarkers (especially using nipple aspirate fluid mirroring breast microenvironment), studies have highlighted an optimal combination of well-known biomarkers: uPA + PAI-1 + TF. When individually investigated they did not show perfect accuracy in predicting the presence of breast cancer, whereas the triple combination has been demonstrated to be highly predictive of pre-cancer and/or cancerous conditions, approaching 97-100% accuracy. Despite the heterogeneous composition of breast cancer and the difficulties to find specific breast cancer biomolecules, the noninvasive analysis of the nipple aspirate fluid secretome may significantly improve the discovery of promising biomarkers, helping also the differentiation among benign and invasive breast diseases, opening new frontiers in early oncoproteomics

  13. Nonsteroidal anti-inflammatory drugs and the risk of developing breast cancer in a population-based prospective cohort study in Washington County, MD.

    Science.gov (United States)

    Gallicchio, Lisa; Visvanathan, Kala; Burke, Alyce; Hoffman, Sandra C; Helzlsouer, Kathy J

    2007-07-01

    The objective of this study was to examine the association between nonsteroidal anti-inflammatory drug (NSAID) use and the development of breast cancer, and to assess whether this association differed by estrogen receptor (ER) subtype. Data were analyzed from 15,651 women participating in CLUE II, a cohort study initiated in 1989 in Washington County, MD. Medication data were collected at baseline in 1989 and in 1996. Incident cases of invasive breast cancer occurring from baseline to March 27, 2006 were identified through linkage of cohort participants with the Washington County Cancer Registry and the Maryland State Cancer Registry. Cox proportional hazards modeling was used to calculate the risk ratios (RR) and 95% confidence intervals (95% CI) for breast cancer associated with medication use. Among women in the CLUE II cohort, 418 invasive breast cancer cases were identified during the follow-up period. The results showed that self-reported use of NSAIDs in both 1989 and in 1996 was associated with a 50% reduction in the risk of developing invasive breast cancer compared with no NSAID use in either 1989 or 1996 (RR = 0.50; 95% CI 0.28, 0.91). The protective association between NSAID use and the risk of developing breast cancer was consistent among ER-positive and ER-negative breast cancers, although only the RR for ER-positive breast cancer was statistically significant. Overall, findings from this study indicate that NSAID use is associated with a decrease in breast cancer risk and that the reduction in risk is similar for ER-positive and ER-negative tumors.

  14. Anti-tumor effects of 125I radioactive particles implantation on transplantated tumor model of human breast cancer cells in nude mice

    International Nuclear Information System (INIS)

    Xiao Zhongdi; Liang Chunlin; Zhang Guoli; Jing Yue; Zhang Yucheng; Gai Baodong

    2011-01-01

    Objective: To study the anti-tumor effects of 125 I radioactive particles implantation on transplantated tumor model of human breast cancer cells in nude mice and clarify their anti-tumor mechanisms. Methods 120 nude mice transplantated with human breast cancer cells MCF-7 were randomly divided into 3 groups (n=40): 125 I radioactive particles implanted group, non-radioactive particles implanted group and non-particles implanted group. The articles were implanted into mice according to Pairs system principle. The expressions of Fas mRNA and protein and the activaties of caspase-3 and caspase-8 enzyme were detected by RT-PCR and Western blotting. The changes of cell cycle were detected by flow cytometry. Results: Compared with non-radioactive particles implanted group and non-particles implanted group, the size of cancer tissues in 125 I radioactive particles implanted group was reduced significantly (P 0 /G 1 phase was significantly increased (P 125 I radioactive particles into transplantated tumor model of human breast cancer cells can kill tumor cells, inhibit the growth cycle of tumor cells and induce the apoptosis of tumor cells in nude mice. (authors)

  15. FoxA1 as a lineage-specific oncogene in luminal type breast cancer

    International Nuclear Information System (INIS)

    Yamaguchi, Noritaka; Ito, Emi; Azuma, Sakura; Honma, Reiko; Yanagisawa, Yuka; Nishikawa, Akira; Kawamura, Mika; Imai, Jun-ichi

    2008-01-01

    The forkhead transcription factor FoxA1 is thought to be involved in mammary tumorigenesis. However, the precise role of FoxA1 in breast cancer development is controversial. We examined expression of FoxA1 in 35 human breast cancer cell lines and compared it with that of ErbB2, a marker of poor prognosis in breast cancer. We found that FoxA1 is expressed at high levels in all ErbB2-positive cell lines and a subset of ErbB2-negative cell lines. Down-regulation of FoxA1 by RNA interference significantly suppressed proliferation of ErbB2-negative and FoxA1-positive breast cancer cell lines. Down-regulation of FoxA1 also enhanced the toxic effect of Herceptin on ErbB2-positive cell lines through induction of apoptosis. Taken together with previous data that FoxA1 is a marker of luminal cells in mammary gland, our present results suggest that FoxA1 plays an important role as a lineage-specific oncogene in proliferation of cancer cells derived from mammary luminal cells

  16. Non-oncogenic Acute Viral Infections Disrupt Anti-cancer Responses and Lead to Accelerated Cancer-Specific Host Death

    Directory of Open Access Journals (Sweden)

    Frederick J. Kohlhapp

    2016-10-01

    Full Text Available In light of increased cancer prevalence and cancer-specific deaths in patients with infections, we investigated whether infections alter anti-tumor immune responses. We report that acute influenza infection of the lung promotes distal melanoma growth in the dermis and leads to accelerated cancer-specific host death. Furthermore, we show that during influenza infection, anti-melanoma CD8+ T cells are shunted from the tumor to the infection site, where they express high levels of the inhibitory receptor programmed cell death protein 1 (PD-1. Immunotherapy to block PD-1 reverses this loss of anti-tumor CD8+ T cells from the tumor and decreases infection-induced tumor growth. Our findings show that acute non-oncogenic infection can promote cancer growth, raising concerns regarding acute viral illness sequelae. They also suggest an unexpected role for PD-1 blockade in cancer immunotherapy and provide insight into the immune response when faced with concomitant challenges.

  17. Breast cancer screening

    International Nuclear Information System (INIS)

    Vandenbroucke, A.

    1987-01-01

    Many studies have shown that breast cancer screening is able to reduce breast cancer mortality, including the HIP study, the Swedish Trial and the Netherlands studies. Mammography is considered as the most effective method for breast cancer screening but it might be unfeasible for some reasons: - the population acceptability of the method might be low. Indeed, most populations of the South of Europe are less compliant to mass screening than populations of the North of Europe; - the medical equipment and personnel - radiologists and pathologists - might be insufficient; - it might be too costly for the National Health Service, specially where the incidence rate of breast cancer is relatively low (i.e. Greece, Portugal). The validity of screening tests is judged by their sensitivity and their specificity

  18. Enhancer-Mediated Oncogenic Function of the Menin Tumor Suppressor in Breast Cancer

    Directory of Open Access Journals (Sweden)

    Koen M.A. Dreijerink

    2017-03-01

    Full Text Available While the multiple endocrine neoplasia type 1 (MEN1 gene functions as a tumor suppressor in a variety of cancer types, we explored its oncogenic role in breast tumorigenesis. The MEN1 gene product menin is involved in H3K4 trimethylation and co-activates transcription. We integrated ChIP-seq and RNA-seq data to identify menin target genes. Our analysis revealed that menin-dependent target gene promoters display looping to distal enhancers that are bound by menin, FOXA1 and GATA3. In this fashion, MEN1 co-regulates a proliferative breast cancer-specific gene expression program in ER+ cells. In primary mammary cells, MEN1 exerts an anti-proliferative function by regulating a distinct expression signature. Our findings clarify the cell-type-specific functions of MEN1 and inform the development of menin-directed treatments for breast cancer.

  19. Decision support system for breast cancer detection using mammograms.

    Science.gov (United States)

    Ganesan, Karthikeyan; Acharya, Rajendra U; Chua, Chua K; Min, Lim C; Mathew, Betty; Thomas, Abraham K

    2013-07-01

    Mammograms are by far one of the most preferred methods of screening for breast cancer. Early detection of breast cancer can improve survival rates to a greater extent. Although the analysis and diagnosis of breast cancer are done by experienced radiologists, there is always the possibility of human error. Interobserver and intraobserver errors occur frequently in the analysis of medical images, given the high variability between every patient. Also, the sensitivity of mammographic screening varies with image quality and expertise of the radiologist. So, there is no golden standard for the screening process. To offset this variability and to standardize the diagnostic procedures, efforts are being made to develop automated techniques for diagnosis and grading of breast cancer images. This article presents a classification pipeline to improve the accuracy of differentiation between normal, benign, and malignant mammograms. Several features based on higher-order spectra, local binary pattern, Laws' texture energy, and discrete wavelet transform were extracted from mammograms. Feature selection techniques based on sequential forward, backward, plus-l-takeaway-r, individual, and branch-and-bound selections using the Mahalanobis distance criterion were used to rank the features and find classification accuracies for combination of several features based on the ranking. Six classifiers were used, namely, decision tree classifier, fisher classifier, linear discriminant classifier, nearest mean classifier, Parzen classifier, and support vector machine classifier. We evaluated our proposed methodology with 300 mammograms obtained from the Digital Database for Screening Mammography and 300 mammograms from the Singapore Anti-Tuberculosis Association CommHealth database. Sensitivity, specificity, and accuracy values were used to compare the performances of the classifiers. Our results show that the decision tree classifier demonstrated an excellent performance compared to

  20. FGFR antagonist induces protective autophagy in FGFR1-amplified breast cancer cell

    International Nuclear Information System (INIS)

    Chen, Yi; Xie, Xiaoyan; Li, Xinyi; Wang, Peiqi; Jing, Qian; Yue, Jiaqi; Liu, Yang; Cheng, Zhong; Li, Jingyi; Song, Haixing; Li, Guoyu; Liu, Rui; Wang, Jinhui

    2016-01-01

    Breast cancer, representing approximately 30% of all gynecological cancer cases diagnosed yearly, is a leading cause of cancer-related mortality for women. Amplification of FGFR1 is frequently observed in breast cancers and is associated with poor prognosis. Though FGFRs have long been considered as anti-cancer drug targets, and a cluster of FGFR antagonists are currently under clinical trials, the precise cellular responses under the treatment of FGFR antagonists remains unclear. Here, we show that PD166866, an FGFR1-selective inhibitor, inhibits proliferation and triggers anoikis in FGFR1-amplified breast cancer cell lines. Notably, we demonstrate that PD166866 induces autophagy in FGFR1-amplified breast cancer cell lines, while blockage of autophagy by Atg5 knockdown further enhances the anti-proliferative activities of PD166866. Moreover, mechanistic study reveals that PD166866 induces autophagy through repressing Akt/mTOR signaling pathway. Together, the present study provides new insights into the molecular mechanisms underlying the anti-tumor activities of FGFR antagonists, and may further assist the FGFRs-based drug discovery. -- Highlights: •FGFR1 antagonist inhibits cell viability in FGFR1-amplified breast cancer cells. •FGFR1 antagonist induces autophagy in FGFR1-amplified breast cancer cells. •FGFR1 antagonist-induced autophagy is protective. •FGFR1 antagonist induces autophagy by inhibiting Akt/mTOR pathway.

  1. FGFR antagonist induces protective autophagy in FGFR1-amplified breast cancer cell

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Yi [The School of Biomedical Sciences, Chengdu Medical College, Chengdu 610083 (China); Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu (China); Xie, Xiaoyan; Li, Xinyi; Wang, Peiqi [State Key Laboratory of Oral Diseases, West China College of Stomatology, Sichuan University (China); Jing, Qian; Yue, Jiaqi; Liu, Yang [The School of Biomedical Sciences, Chengdu Medical College, Chengdu 610083 (China); Cheng, Zhong [Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu (China); Li, Jingyi, E-mail: li--jingyi@hotmail.com [The School of Biomedical Sciences, Chengdu Medical College, Chengdu 610083 (China); Song, Haixing [The School of Biomedical Sciences, Chengdu Medical College, Chengdu 610083 (China); Li, Guoyu, E-mail: liguoyulisa@163.com [School of Pharmacy, Shihezi University, Shihezi 832003 (China); Liu, Rui, E-mail: liurui_scu@hotmail.com [State Key Laboratory of Oral Diseases, West China College of Stomatology, Sichuan University (China); Wang, Jinhui [School of Pharmacy, Shihezi University, Shihezi 832003 (China)

    2016-05-20

    Breast cancer, representing approximately 30% of all gynecological cancer cases diagnosed yearly, is a leading cause of cancer-related mortality for women. Amplification of FGFR1 is frequently observed in breast cancers and is associated with poor prognosis. Though FGFRs have long been considered as anti-cancer drug targets, and a cluster of FGFR antagonists are currently under clinical trials, the precise cellular responses under the treatment of FGFR antagonists remains unclear. Here, we show that PD166866, an FGFR1-selective inhibitor, inhibits proliferation and triggers anoikis in FGFR1-amplified breast cancer cell lines. Notably, we demonstrate that PD166866 induces autophagy in FGFR1-amplified breast cancer cell lines, while blockage of autophagy by Atg5 knockdown further enhances the anti-proliferative activities of PD166866. Moreover, mechanistic study reveals that PD166866 induces autophagy through repressing Akt/mTOR signaling pathway. Together, the present study provides new insights into the molecular mechanisms underlying the anti-tumor activities of FGFR antagonists, and may further assist the FGFRs-based drug discovery. -- Highlights: •FGFR1 antagonist inhibits cell viability in FGFR1-amplified breast cancer cells. •FGFR1 antagonist induces autophagy in FGFR1-amplified breast cancer cells. •FGFR1 antagonist-induced autophagy is protective. •FGFR1 antagonist induces autophagy by inhibiting Akt/mTOR pathway.

  2. Integrated Immunotherapy for Breast Cancer

    Science.gov (United States)

    2016-09-01

    TITLE AND SUBTITLE 5a. CONTRACT NUMBER Integrated Immunotherapy for Breast Cancer 5b. GRANT NUMBER W81XWH-12-1-0366 5c. PROGRAM ELEMENT...communications 215, 566 (Oct 13, 1995). 87. S. J. Reshkin, R. A. Cardone , S. Harguindey, Na+-H+ exchanger, pH regulation and cancer. Recent patents on anti-cancer drug discovery 8, 85 (Jan 1, 2013).

  3. Early breast cancer

    International Nuclear Information System (INIS)

    Dongen, J.A. van

    1989-01-01

    The therapy of early breast cancer has been changing during the last decennium. It requires a multi-disciplinary approach and in each of these disciplines improvements have been implemented. The result is that treatment schedules can now be adapted to specific subgroups. In this review early breast cancer is defined as operable disease, using the criteria set out by Haagensen. Emphasis is given to describing the new developments in prognostic criteria, since these form the basis for creating subgroups for specific treatment schedules. Distinction is made between the factors relating to growth rate and those relating to metastatic potential. Data on screening promises a beneficial effect of the implementation of screening in national health care programs. Important shifts are seen in treatment schedules; the place of postoperative radiotherapy after classic ablative treatment is being challenged, whereas it plays a major role in the new breast conserving therapy schedules. The data mentioned in the review suggest that a large proportion of 'operable' cases can be treated with breast conservation but details in the technique of breast conserving therapy are still under investigation. They form a major part of the coming prospective studies in breast cancer. Improvements in reconstruction techniques, creating better cosmetic results, make reconstruction more competitive with breast conserving therapy. The use of chemotherapy and endocrine manipulation in early breast cancer has now been clearly confirmed by the overview technique by the Peto-group, thanks to all efforts of individual trialists together. (orig.)

  4. Anti-HER2 antibody and ScFvEGFR-conjugated antifouling magnetic iron oxide nanoparticles for targeting and magnetic resonance imaging of breast cancer

    Directory of Open Access Journals (Sweden)

    Chen H

    2013-10-01

    Full Text Available Hongwei Chen,1,* Liya Wang,1,2,* Qiqi Yu,1,2 Weiping Qian,3 Diana Tiwari,1 Hong Yi,4 Andrew Y Wang,5 Jing Huang,1,2 Lily Yang,3 Hui Mao1,2 1Department of Radiology and Imaging Sciences, 2Center for Systems Imaging, 3Department of Surgery, Emory University School of Medicine, 4Robert Apkarian Electron Microscopy Core, Emory University, Atlanta, GA, 5Ocean NanoTech LLC, Springdale, AK, USA *These authors contributed equally to this work Abstract: Antifouling magnetic iron oxide nanoparticles (IONPs coated with block copolymer poly(ethylene oxide-block-poly(γ-methacryloxypropyltrimethoxysilane (PEO-b-PγMPS were investigated for improving cell targeting by reducing nonspecific uptake. Conjugation of a HER2 antibody, Herceptin®, or a single chain fragment (ScFv of antibody against epidermal growth factor receptor (ScFvEGFR to PEO-b-PγMPS-coated IONPs resulted in HER2-targeted or EGFR-targeted IONPs (anti-HER2-IONPs or ScFvEGFR-IONPs. The anti-HER2-IONPs bound specifically to SK-BR-3, a HER2-overexpressing breast cancer cell line, but not to MDA-MB-231, a HER2-underexpressing cell line. On the other hand, the ScFvEGFR-IONPs showed strong reactivity with MDA-MB-231, an EGFR-positive human breast cancer cell line, but not with MDA-MB-453, an EGFR-negative human breast cancer cell line. Transmission electron microscopy revealed internalization of the receptor-targeted nanoparticles by the targeted cancer cells. In addition, both antibody-conjugated and non-antibody-conjugated IONPs showed reduced nonspecific uptake by RAW264.7 mouse macrophages in vitro. The developed IONPs showed a long blood circulation time (serum half-life 11.6 hours in mice and low accumulation in both the liver and spleen. At 24 hours after systemic administration of ScFvEGFR-IONPs into mice bearing EGFR-positive breast cancer 4T1 mouse mammary tumors, magnetic resonance imaging revealed signal reduction in the tumor as a result of the accumulation of the targeted IONPs

  5. Fluorescein isothiocyanate labeled, magnetic nanoparticles conjugated D-penicillamine-anti-metadherin and in vitro evaluation on breast cancer cells

    International Nuclear Information System (INIS)

    Akca, Ozlet; Unak, Perihan; Medine, E. Ylker; Sakarya, Serhan; Ozdemir, Caglar; Timur, Suna

    2011-01-01

    Silane modified magnetic nanoparticles were prepared after capped with silica generated from the hydrolyzation of tetraethyl orthosilicate (TEOS). Amino silane (SG-Si900) was added to this solution for surface modification of silica coated magnetic particles. Finally, D-penicillamine (D-PA)-antimetadherin (anti-MTDH) was covalently linked to the amine group using glutaraldehyde as cross-linker. Magnetic nanoparticles were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), vibrating sample magnetometer (VSM), and atomic force microscopy (AFM). AFM results showed that particles are nearly monodisperse, and the average size of particles was 40 to 50 nm. An amino acid derivative D-PA was conjugated anti-MTDH, which results the increase of uptaking potential of a conjugated agent, labelled fluorescein isothiocyanate (FITC) and then conjugated to the magnetic nanoparticles. In vitro evaluation of the conjugated D-PA-anti-MTDH-FITC to magnetic nanoparticle was studied on MCF-7 breast cancer cell lines. Fluorescence microscopy images of cells after incubation of the sample were obtained to monitor the interaction of the sample with the cancerous cells. Incorporation on cells of FITC labeled and magnetic nanoparticles conjugated D-PA-anti-MTDH was found higher than FITC labeled D-PA-anti-MTDH. The results show that magnetic properties and application of magnetic field increased incorporation rates. The obtained D-PA-anti-MTDH-magnetic nanoparticles-FITC complex has been used for in vitro imaging of breast cancer cells. FITC labeled and magnetic nanoparticles conjugated D-PA-anti-MTDH may be useful as a new class of scintigraphic agents. Results of this study are sufficiently encouraging to bring about further evaluation of this and related compounds for ultraviolet magnetic resonance (UV-MR) dual imaging. (author)

  6. Growth of MCF-7 breast cancer cells and efficacy of anti-angiogenic agents in a hydroxyethyl chitosan/glycidyl methacrylate hydrogel.

    Science.gov (United States)

    Wang, Hejing; Qian, Junmin; Zhang, Yaping; Xu, Weijun; Xiao, Juxiang; Suo, Aili

    2017-01-01

    Breast cancer negatively affects women's health worldwide. The tumour microenvironment plays a critical role in tumour initiation, proliferation, and metastasis. Cancer cells are traditionally grown in two-dimensional (2D) cultures as monolayers on a flat solid surface lacking cell-cell and cell-matrix interactions. These experimental conditions deviate from the clinical situation. Improved experimental systems that can mimic the in vivo situation are required to discover new therapies, particularly for anti-angiogenic agents that mainly target intercellular factors and play an essential role in treating some cancers. Chitosan can be modified to construct three-dimensional (3D) tumour models. Here, we report an in vitro 3D tumour model using a hydroxyethyl chitosan/glycidyl methacrylate (HECS-GMA) hydrogel produced by a series of chitosan modifications. Parameters relating to cell morphology, viability, proliferation, and migration were analysed using breast cancer MCF-7 cells. In a xenograft model, secretion of angiogenesis-related growth factors and the anti-angiogenic efficacy of Endostar and Bevacizumab in cells grown in HECS-GMA hydrogels were assessed by immunohistochemistry. Hydroxyethyl chitosan/glycidyl methacrylate hydrogels had a highly porous microstructure, mechanical properties, swelling ratio, and morphology consistent with a 3D tumour model. Compared with a 2D monolayer culture, breast cancer MCF-7 cells residing in the HECS-GMA hydrogels grew as tumour-like clusters in a 3D formation. In a xenograft model, MCF-7 cells cultured in the HECS-GMA hydrogels had increased secretion of angiogenesis-related growth factors. Recombinant human endostatin (Endostar), but not Bevacizumab (Avastin), was an effective anti-angiogenic agent in HECS-GMA hydrogels. The HECS-GMA hydrogel provided a 3D tumour model that mimicked the in vivo cancer microenvironment and supported the growth of MCF7 cells better than traditional tissue culture plates. The HECS

  7. Anti-proliferative and apoptosis-inducing activity of lycopene against three subtypes of human breast cancer cell lines

    Science.gov (United States)

    Takeshima, Mikako; Ono, Misaki; Higuchi, Takako; Chen, Chen; Hara, Takayuki; Nakano, Shuji

    2014-01-01

    Although lycopene, a major carotenoid component of tomatoes, has been suggested to attenuate the risk of breast cancer, the underlying preventive mechanism remains to be determined. Moreover, it is not known whether there are any differences in lycopene activity among different subtypes of human breast cancer cells. Using ER/PR positive MCF-7, HER2-positive SK-BR-3 and triple-negative MDA-MB-468 cell lines, we investigated the cellular and molecular mechanism of the anticancer activity of lycopene. Lycopene treatment for 168 consecutive hours exhibited a time-dependent and dose-dependent anti-proliferative activity against these cell lines by arresting the cell cycle at the G0/G1 phase at physiologically achievable concentrations found in human plasma. The greatest growth inhibition was observed in MDA-MB-468 where the sub-G0/G1 apoptotic population was significantly increased, with demonstrable cleavage of PARP. Lycopene induced strong and sustained activation of the ERK1/2, with concomitant cyclin D1 suppression and p21 upregulation in these three cell lines. In triple negative cells, lycopene inhibited the phosphorylation of Akt and its downstream molecule mTOR, followed by subsequent upregulation of proapoptotic Bax without affecting anti-apoptotic Bcl-xL. Taken together, these data indicate that the predominant anticancer activity of lycopene in MDA-MB-468 cells suggests a potential role of lycopene for the prevention of triple negative breast cancer. PMID:24397737

  8. Breast cancer and breast health awareness as an evolving health promotion concept

    International Nuclear Information System (INIS)

    Plesnicar, A.; Kralj, B.; Kovac, V.

    2004-01-01

    Background. Breast cancer is the most frequent malignant disease in the majority of developed countries. In the last few years the introduction of mammography screening programmes has resulted in an improved survival of breast cancer patients. However, the incidence of the disease in these countries is still on the increase. Present focus on secondary breast cancer prevention activities, consisting of early detection and treatment, cannot ensure a decrease of breast cancer incidence. Improved breast health awareness could therefore represent a part of specific health promotion activities aimed at decreasing the incidence of breast cancer. Conclusions. In developed countries breast cancer is a significant health care issue. Secondary breast cancer prevention activities should therefore be complemented by specific health promotion activities in order to reduce its incidence in the future. Primary breast cancer prevention would include health promotion activities aimed at enhancement of the individual as well as collective breast health awareness. Properly enlightened members of the influential population groups could attain appropriate changes in the fields of legislation, taxation, customs and commercial regulations that would enable women to control their own breast health. (author)

  9. Retrospective observation on contribution and limitations of screening for breast cancer with mammography in Korea: detection rate of breast cancer and incidence rate of interval cancer of the breast.

    Science.gov (United States)

    Lee, Kunsei; Kim, Hyeongsu; Lee, Jung Hyun; Jeong, Hyoseon; Shin, Soon Ae; Han, Taehwa; Seo, Young Lan; Yoo, Youngbum; Nam, Sang Eun; Park, Jong Heon; Park, Yoo Mi

    2016-11-18

    The purpose of this study was to determine the benefits and limitations of screening for breast cancer using mammography. Descriptive design with follow-up was used in the study. Data from breast cancer screening and health insurance claim data were used. The study population consisted of all participants in breast cancer screening from 2009 to 2014. Crude detection rate, positive predictive value and sensitivity and specificity of breast cancer screening and, incidence rate of interval cancer of the breast were calculated. The crude detection rate of breast cancer screening per 100,000 participants increased from 126.3 in 2009 to 182.1 in 2014. The positive predictive value of breast cancer screening per 100,000 positives increased from 741.2 in 2009 to 1,367.9 in 2014. The incidence rate of interval cancer of the breast per 100,000 negatives increased from 51.7 in 2009 to 76.3 in 2014. The sensitivities of screening for breast cancer were 74.6% in 2009 and 75.1% in 2014 and the specificities were 83.1% in 2009 and 85.7% in 2014. To increase the detection rate of breast cancer by breast cancer screening using mammography, the participation rate should be higher and an environment where accurate mammography and reading can be performed and reinforcement of quality control are required. To reduce the incidence rate of interval cancer of the breast, it will be necessary to educate women after their 20s to perform self-examination of the breast once a month regardless of participation in screening for breast cancer.

  10. Effects of biosurfactants on the viability and proliferation of human breast cancer cells.

    Science.gov (United States)

    Duarte, Cristina; Gudiña, Eduardo J; Lima, Cristovao F; Rodrigues, Ligia R

    2014-01-01

    Biosurfactants are molecules with surface activity produced by microorganisms that can be used in many biomedical applications. The anti-tumour potential of these molecules is being studied, although results are still scarce and few data are available regarding the mechanisms underlying such activity. In this work, the anti-tumour activity of a surfactin produced by Bacillus subtilis 573 and a glycoprotein (BioEG) produced by Lactobacillus paracasei subsp. paracasei A20 was evaluated. Both biosurfactants were tested against two breast cancer cell lines, T47D and MDA-MB-231, and a non-tumour fibroblast cell line (MC-3 T3-E1), specifically regarding cell viability and proliferation. Surfactin was found to decrease viability of both breast cancer cell lines studied. A 24 h exposure to 0.05 g l(-1) surfactin led to inhibition of cell proliferation as shown by cell cycle arrest at G1 phase. Similarly, exposure of cells to 0.15 g l(-1) BioEG for 48 h decreased cancer cells' viability, without affecting normal fibroblasts. Moreover, BioEG induced the cell cycle arrest at G1 for both breast cancer cell lines. The biosurfactant BioEG was shown to be more active than surfactin against the studied breast cancer cells. The results gathered in this work are very promising regarding the biosurfactants potential for breast cancer treatment and encourage further work with the BioEG glycoprotein.

  11. 19p13.1 is a triple-negative-specific breast cancer susceptibility locus

    DEFF Research Database (Denmark)

    Stevens, Kristen N; Fredericksen, Zachary; Vachon, Celine M

    2012-01-01

    (PR), and human epidermal growth factor receptor-2 (HER2) status, using 48,869 breast cancer cases and 49,787 controls from the Breast Cancer Association Consortium (BCAC). Variants from 19p13.1 were not associated with breast cancer overall or with ER-positive breast cancer but were significantly......The 19p13.1 breast cancer susceptibility locus is a modifier of breast cancer risk in BRCA1 mutation carriers and is also associated with the risk of ovarian cancer. Here, we investigated 19p13.1 variation and risk of breast cancer subtypes, defined by estrogen receptor (ER), progesterone receptor...... associated with ER-negative breast cancer risk [rs8170 OR, 1.10; 95% confidence interval (CI), 1.05-1.15; P = 3.49 × 10(-5)] and triple-negative (ER-, PR-, and HER2-negative) breast cancer (rs8170: OR, 1.22; 95% CI, 1.13-1.31; P = 2.22 × 10(-7)). However, rs8170 was no longer associated with ER...

  12. Cordycepin, a Natural Antineoplastic Agent, Induces Apoptosis of Breast Cancer Cells via Caspase-dependent Pathways.

    Science.gov (United States)

    Wang, Di; Zhang, Yongfeng; Lu, Jiahui; Wang, Yang; Wang, Junyue; Meng, Qingfan; Lee, Robert J; Wang, Di; Teng, Lesheng

    2016-01-01

    Cordycepin, a major compound separated from Cordyceps sinensis, is known as a potential novel candidate for cancer therapy. Breast cancer, the most typical cancer diagnosed among women, remains a global health problem. In this study, the anti-breast cancer property of cordycepin and its underlying mechanisms was investigated. The direct effects of cordycepin on breast cancer cells both in in vitro and in vivo experiments were evaluated. Cordycepin exerted cytotoxicity in MCF-7 and MDA-MB-231 cells confirmed by reduced cell viability, inhibition of cell proliferation, enhanced lactate dehydrogenase release and reactive oxygen species accumulation, induced mitochondrial dysfunction and nuclear apoptosis in human breast cancer cells. Cordycepin increased the activation of pro-apoptotic proteins, including caspase-8, caspase-9, caspase-3 and Bax, and suppressed the expression of the anti-apoptotic protein, B-cell lymphoma 2 (Bcl-2). The inhibition on MCF-7-xenografted tumor growth in nude mice further confirmed cordycepin's anti-breast cancer effect. These aforementioned results reveal that cordycepin induces apoptosis in human breast cancer cells via caspase-dependent pathways. The data shed light on the possibility of cordycepin being a safe agent for breast cancer treatment.

  13. Breast cancer in atomic bomb survivors

    International Nuclear Information System (INIS)

    Tokunga, M.; Land, C.E.; Tokuoka, S.

    1986-01-01

    Thirty eight years after the atomic bombings, studies of the Radiation Effects Research Foundation (RERF) on the extended Life Span Study (LSS) sample have continued to provide important information on radiation carcinogenesis. The third breast cancer survey among this sample revealed 564 cases during the period 1950-80, of which 412 were reviewed microscopically. The following statements reflect the conclusions from the current investigation; 1) the relationship between radiation dose and breast cancer incidence was consistent with linearity and did not differ markedly between the Hiroshima and Nagasaki survivors, 2) a dose-related breast cancer risk was observed among women who were in their first decade of life at the time of exposure, 3) the relative risk of radiationinduced breast cancer decreased with increasing age at exposure, 4) the pattern over time of age-specific breast cancer incidence is similar for exposed and control women (that is, exposed women have more breast cancer than control women but the excess risk closely follows normal risk as expressed by age-specific population rates), and 5) radiation-induced breast cancer appears to be morphologically similar to other breast cancer

  14. Breast cancer in atomic bomb survivors

    International Nuclear Information System (INIS)

    Tokunaga, Masayoshi; Tokuoka, Shoji; Land, C.E.

    1986-01-01

    Thirty eight years after the atomic bombings, studies of the Radiation Effects Research Foundation (RERF) on the extended Life Span Study (LSS) sample have continued to provide important information on radiation carcinogenesis. The third breast cancer survey among this sample revealed 564 cases during the period 1950 - 80, of which 412 were reviewed microscopically. The following statements reflect the conclusions from the current investigation; 1) the relationship between radiation dose and breast cancer incidence was consistent with linearity and did not differ markedly between the Hiroshima and Nagasaki survivors, 2) a dose-related breast cancer risk was observed among women who were in their first decade of life at the time of exposure, 3) the relative risk of radiation-induced breast cancer decreased with increasing age at exposure, 4) the pattern over time of age-specific breast cancer incidence is similar for exposed and control women (that is, exposed women have more breast cancer than control women but the excess risk closely follows normal risk as expressed by age-specific population rates), and 5) radiation-induced breast cancer appears to be morphologically similar to other breast cancer. (author)

  15. Development of a Targeted anti-HER2 scFv Chimeric Peptide for Gene Delivery into HER2-Positive Breast Cancer Cells.

    Science.gov (United States)

    Cheraghi, Roya; Nazari, Mahboobeh; Alipour, Mohsen; Majidi, Asia; Hosseinkhani, Saman

    2016-12-30

    Chimeric polymers are known as suitable carriers for gene delivery. Certain properties are critical for a polymer to be used as a gene delivery vector. A new polymer was designed for the targeted delivery of genes into breast cancer cell lines, based on MPG peptide. It is composed of different functional domains, including HIV gp41, nuclear localization sequence of SV40 T-antigen, two C-terminus repeats of histone H1, and the scFv of anti-HER2 antibody. The results demonstrated that the vector can effectively condense plasmid DNA into nanoparticles with an average size of 250nm. Moreover, fusion of the scFv portion to the carrier brought about the specific recognition of HER2. Overall, the transfection efficiency of the vector demonstrated that it could deliver the desired gene into BT-474 HER2-positive breast cancer cells. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Re-evaluation of the prolactin receptor expression in human breast cancer

    DEFF Research Database (Denmark)

    Galsgaard, Elisabeth Douglas; Rasmussen, Birgitte Bruun; Folkesson, Charlotta Grånäs

    2009-01-01

    , we evaluated the specificity of commercially available anti-human PRLR antibodies (B6.2, U5, PRLRi pAb, 1A2B1, 250448 and H-300). The latter three antibodies were found to specifically recognise PRLR. The relative PRLR expression level detected with these antibodies closely reflected the level...... to be sufficient to mediate PRL responsiveness in breast cancer cell lines....

  17. ONC201 demonstrates anti-tumor effects in both triple negative and non-triple negative breast cancers through TRAIL-dependent and TRAIL-independent mechanisms

    Science.gov (United States)

    Ralff, Marie D.; Kline, Christina L.B.; Küçükkase, Ozan C; Wagner, Jessica; Lim, Bora; Dicker, David T.; Prabhu, Varun V.; Oster, Wolfgang; El-Deiry, Wafik S.

    2017-01-01

    Breast cancer is a major cause of cancer-related death. TRAIL has been of interest as a cancer therapeutic, but only a subset of triple negative breast cancers (TNBC) is sensitive to TRAIL. The small molecule ONC201 induces expression of TRAIL and its receptor DR5. ONC201 has entered clinical trials in advanced cancers. Here we show that ONC201 is efficacious against both TNBC and non-TNBC cells (n=13). A subset of TNBC and non-TNBC cells succumb to ONC201-induced cell death. In 2/8 TNBC cell lines, ONC201 treatment induces caspase-8 cleavage and cell death that is blocked by TRAIL-neutralizing antibody RIK2. The pro-apoptotic effect of ONC201 translates to in vivo efficacy in the MDA-MB-468 xenograft model. In most TNBC lines tested (6/8) ONC201 has an anti-proliferative effect but does not induce apoptosis. ONC201 decreases cyclin D1 expression and causes an accumulation of cells in the G1 phase of the cell cycle. pRb expression is associated with sensitivity to the anti-proliferative effects of ONC201, and the compound synergizes with taxanes in less sensitive cells. All non-TNBC cells (n=5) are growth inhibited following ONC201 treatment, and unlike what has been observed with TRAIL, a subset (n=2) show PARP cleavage. In these cells, cell death induced by ONC201 is TRAIL-independent. Our data demonstrate that ONC201 has potent anti-proliferative and pro-apoptotic effects in a broad range of breast cancer subtypes, through TRAIL-dependent and TRAIL-independent mechanisms. These findings develop a pre-clinical rationale for developing ONC201 as a single agent and/or in combination with approved therapies in breast cancer. PMID:28424227

  18. The anti-cancer effect of octagon and spherical silver nanoparticles on MCF-7 breast cancer cell line

    Directory of Open Access Journals (Sweden)

    Mehrdad Khatami

    2017-04-01

    Full Text Available Background: The modern science of nanotechnology is an interdisciplinary science that has contributed to advances in cancer treatment. This study was performed to evaluate the therapeutic effects of biosynthesized silver nanoparticles on breast cancer cell of line MCF-7 in vitro. Methods: This analytical study was performed in Kerman and Bam University of Medical Sciences, Bam City, Kerman Province, Iran from March 2015 to March 2016. Silver nanoparticles suspension was synthesized using palm kernel extract. The resulting silver nanoparticles were studied and characterized. The ultraviolet-visible spectroscopy and transmission electron microscopy used for screening of physicochemical properties. The average particle size of the biosynthesized silver nanoparticles was determined by transmission electron microscopy. The properties of different concentrations of synthesized silver nanoparticles (1 to 3 μg/ml and palm kernel extract (containing the same concentration of the extract was used for the synthesis of silver nanoparticles against MCF-7 human breast cancer cells were determined by MTT assay. MTT is used to assess cell viability as a function of redox potential. Actively respiring cells convert the water-soluble MTT to an insoluble purple formazan. Results: The ultraviolet-visible spectroscopy showed strong absorption peak at 429 nm. The X-ray diffraction (XRD and transmission electron microscopy (TEM images revealed the formation of silver nanoparticles with spherical and octagon shape and sizes in the range between 1-40 nm, with an average size approximately 17 nm. The anti-cancer effect of silver nanoparticles on cell viability was strongly depends on the concentration of silver nanoparticles and greatly decrease with increasing the concentration of silver nanoparticles. The IC50 amount of silver nanoparticle was 2 μg/ml. Conclusion: The biosynthesized silver nanoparticles showed a dose-dependent toxicity against MCF-7 human breast

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

    International Nuclear Information System (INIS)

    Rashid-Kolvear, Fariborz; Taboski, Michael AS; Nguyen, Johnny; Wang, Dong-Yu; Harrington, Lea A; Done, Susan J

    2010-01-01

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

  20. Validated biomarkers: The key to precision treatment in patients with breast cancer.

    Science.gov (United States)

    Duffy, Michael J; O'Donovan, Norma; McDermott, Enda; Crown, John

    2016-10-01

    Recent DNA sequencing and gene expression studies have shown that at a molecular level, almost every case of breast cancer is unique and different from other breast cancers. For optimum management therefore, every patient should receive treatment that is guided by the molecular composition of their tumor, i.e., precision treatment. While such a scenario is still some distance into the future, biomarkers are beginning to play an important role in preparing the way for precision treatment. In particular, biomarkers are increasingly being used for predicting patient outcome and informing as to the most appropriate type of systemic therapy to be administered. Mandatory biomarkers for every newly diagnosed case of breast cancer are estrogen receptors and progesterone receptors in selecting patients for endocrine treatment and HER2 for identifying patients likely to benefit from anti-HER2 therapy. Amongst the best validated prognostic biomarker tests are uPA/PAI-1, MammaPrint and Oncotype DX. Although currently, there are no biomarkers available for predicting response to specific forms of chemotherapy, uPA/PAI-1 and Oncotype DX can aid the identification of lymph node-negative patients that are most likely to benefit from adjuvant chemotherapy, in general. In order to accelerate progress towards precision treatment for women with breast cancer, we need additional predictive biomarkers, especially for enhancing the positive predictive value for endocrine and anti-HER2 therapies, as well as biomarkers for predicting response to specific forms of chemotherapy. The ultimate biomarker test for achieving the goal of precision treatment for patients with breast cancer will likely require a combination of gene sequencing and transcriptomic analysis of every patient's tumor. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Role of tumor microenvironment in triple-negative breast cancer and its prognostic significance

    Institute of Scientific and Technical Information of China (English)

    Tianjian Yu; Genhong Di

    2017-01-01

    Breast cancer has been shown to live in the tumor microenvironment,which consists of not only breast cancer cells themselves but also a significant amount of pathophysiologically altered surrounding stroma and cells.Diverse components of the breast cancer microenvironment,such as suppressive immune cells,re-programmed fibroblast cells,altered extracellular matrix (ECM) and certain soluble factors,synergistically impede an effective anti-tumor response and promote breast cancer progression and metastasis.Among these components,stromal cells in the breast cancer microenvironment are characterized by molecular alterations and aberrant signaling pathways,whereas the ECM features biochemical and biomechanical changes.However,triple-negative breast cancer (TNBC),the most aggressive subtype of this disease that lacks effective therapies available for other subtypes,is considered to feature a unique microenvironment distinct from that of other subtypes,especially compared to Luminal A subtype.Because these changes are now considered to significantly impact breast cancer development and progression,these unique alterations may serve as promising prognostic factors of clinical outcome or potential therapeutic targets for the treatment of TNBC.In this review,we focus on the composition of the TNBC microenvironment,concomitant distinct biological alteration,specific interplay between various cell types and TNBC cells,and the prognostic implications of these findings.

  2. Relationship of Predicted Risk of Developing Invasive Breast Cancer, as Assessed with Three Models, and Breast Cancer Mortality among Breast Cancer Patients.

    Directory of Open Access Journals (Sweden)

    Mark E Sherman

    Full Text Available Breast cancer risk prediction models are used to plan clinical trials and counsel women; however, relationships of predicted risks of breast cancer incidence and prognosis after breast cancer diagnosis are unknown.Using largely pre-diagnostic information from the Breast Cancer Surveillance Consortium (BCSC for 37,939 invasive breast cancers (1996-2007, we estimated 5-year breast cancer risk (<1%; 1-1.66%; ≥1.67% with three models: BCSC 1-year risk model (BCSC-1; adapted to 5-year predictions; Breast Cancer Risk Assessment Tool (BCRAT; and BCSC 5-year risk model (BCSC-5. Breast cancer-specific mortality post-diagnosis (range: 1-13 years; median: 5.4-5.6 years was related to predicted risk of developing breast cancer using unadjusted Cox proportional hazards models, and in age-stratified (35-44; 45-54; 55-69; 70-89 years models adjusted for continuous age, BCSC registry, calendar period, income, mode of presentation, stage and treatment. Mean age at diagnosis was 60 years.Of 6,021 deaths, 2,993 (49.7% were ascribed to breast cancer. In unadjusted case-only analyses, predicted breast cancer risk ≥1.67% versus <1.0% was associated with lower risk of breast cancer death; BCSC-1: hazard ratio (HR = 0.82 (95% CI = 0.75-0.90; BCRAT: HR = 0.72 (95% CI = 0.65-0.81 and BCSC-5: HR = 0.84 (95% CI = 0.75-0.94. Age-stratified, adjusted models showed similar, although mostly non-significant HRs. Among women ages 55-69 years, HRs approximated 1.0. Generally, higher predicted risk was inversely related to percentages of cancers with unfavorable prognostic characteristics, especially among women 35-44 years.Among cases assessed with three models, higher predicted risk of developing breast cancer was not associated with greater risk of breast cancer death; thus, these models would have limited utility in planning studies to evaluate breast cancer mortality reduction strategies. Further, when offering women counseling, it may be useful to note that high

  3. Late effects of breast cancer treatment and potentials for rehabilitation

    Energy Technology Data Exchange (ETDEWEB)

    Ewertz, Marianne (Dept. of Oncology, Odense Univ. Hospital, Odense (Denmark)); Bonde Jensen, Anders (Inst. of Clinical Research, Univ. of Southern Denmark (Denmark))

    2011-02-15

    Background. Breast cancer is the most frequent malignant disease among women world wide. Survival has been improving leading to an increasing number of breast cancer survivors, in the US estimated to about 2.6 million. Material and methods. The literature was reviewed with focus on data from the Nordic countries. Results. Local therapies such as breast cancer surgery and radiotherapy may cause persistent pain in the breast area, arm, and shoulder reported by 30-50% of patients after three to five years, lymphedema in 15-25% of patients, and restrictions of arm and shoulder movement in 35%. Physiotherapy is the standard treatment for the latter while no pain intervention trials have been published. Chemotherapy may cause infertility and premature menopause, resulting in vasomotor symptoms, sexual dysfunction, and osteoporosis, which are similar to the side effects of endocrine treatment in postmenopausal women. Awareness of cardiotoxicity is needed since anthracyclines, trastuzumab, and radiotherapy can damage the heart. Breast cancer survivors have an increased risk of a major depression and far from all receive adequate anti-depressive treatment. Other psychological symptoms include fear of recurrence, sleep disturbances, cognitive problems, fatigue, and sexual problems. Discussion. To improve rehabilitation, specific goals have to be formulated into national guidelines and high priority directed towards research into developing and testing new interventions for alleviating symptoms and side effects experienced by breast cancer survivors

  4. Late effects of breast cancer treatment and potentials for rehabilitation

    International Nuclear Information System (INIS)

    Ewertz, Marianne; Bonde Jensen, Anders

    2011-01-01

    Background. Breast cancer is the most frequent malignant disease among women world wide. Survival has been improving leading to an increasing number of breast cancer survivors, in the US estimated to about 2.6 million. Material and methods. The literature was reviewed with focus on data from the Nordic countries. Results. Local therapies such as breast cancer surgery and radiotherapy may cause persistent pain in the breast area, arm, and shoulder reported by 30-50% of patients after three to five years, lymphedema in 15-25% of patients, and restrictions of arm and shoulder movement in 35%. Physiotherapy is the standard treatment for the latter while no pain intervention trials have been published. Chemotherapy may cause infertility and premature menopause, resulting in vasomotor symptoms, sexual dysfunction, and osteoporosis, which are similar to the side effects of endocrine treatment in postmenopausal women. Awareness of cardiotoxicity is needed since anthracyclines, trastuzumab, and radiotherapy can damage the heart. Breast cancer survivors have an increased risk of a major depression and far from all receive adequate anti-depressive treatment. Other psychological symptoms include fear of recurrence, sleep disturbances, cognitive problems, fatigue, and sexual problems. Discussion. To improve rehabilitation, specific goals have to be formulated into national guidelines and high priority directed towards research into developing and testing new interventions for alleviating symptoms and side effects experienced by breast cancer survivors

  5. Development of an Anti-HER2 Monoclonal Antibody H2Mab-139 Against Colon Cancer.

    Science.gov (United States)

    Kaneko, Mika K; Yamada, Shinji; Itai, Shunsuke; Kato, Yukinari

    2018-02-01

    Human epidermal growth factor receptor 2 (HER2) expression has been reported in several cancers, such as breast, gastric, lung, pancreatic, and colorectal cancers. HER2 is overexpressed in those cancers and is associated with poor clinical outcomes. Trastuzumab, a humanized anti-HER2 antibody, provides significant survival benefits for patients with HER2-overexpressing breast cancers and gastric cancers. In this study, we developed a novel anti-HER2 monoclonal antibody (mAb), H 2 Mab-139 (IgG 1 , kappa) and investigated it against colon cancers using flow cytometry, western blot, and immunohistochemical analyses. Flow cytometry analysis revealed that H 2 Mab-139 reacted with colon cancer cell lines, such as Caco-2, HCT-116, HCT-15, HT-29, LS 174T, COLO 201, COLO 205, HCT-8, SW1116, and DLD-1. Although H 2 Mab-139 strongly reacted with LN229/HER2 cells on the western blot, we did not observe a specific signal for HER2 in colon cancer cell lines. Immunohistochemical analyses revealed sensitive and specific reactions of H 2 Mab-139 against colon cancers, indicating that H 2 Mab-139 is useful in detecting HER2 overexpression in colon cancers using flow cytometry and immunohistochemical analyses.

  6. Primary breast cancer tumours contain high amounts of IgA1 immunoglobulin

    DEFF Research Database (Denmark)

    Welinder, Charlotte; Baldetorp, Bo; Blixt, Klas Ola

    2013-01-01

    seen in the percentage of stained cells and in the staining pattern in the different breast cancers analysed. Anti-Tn antibody and HPA were also shown to specifically bind to a number of possible constellations of the Tn antigen in the hinge region of IgA1. Both reagents could also detect the presence....... The short O-glycan that forms the antigen is carried by a number of different proteins. One potential carrier of the Tn antigen is immunoglobulin A1 (IgA1), which we surprisingly found in tumour cells of the invasive parts of primary breast carcinoma. Conventional immunohistochemical analysis of paraffin......-embedded sections from primary breast cancers showed IgA1 to be present in the cytoplasm and plasma membrane of 35 out of 36 individual primary tumours. The immunohistochemical staining of HPA and anti-Tn antibody (GOD3-2C4) did to some extent overlap with the presence of IgA1 in the tumours, but differences were...

  7. Genome-wide association studies identify four ER negative-specific breast cancer risk loci.

    Science.gov (United States)

    Garcia-Closas, Montserrat; Couch, Fergus J; Lindstrom, Sara; Michailidou, Kyriaki; Schmidt, Marjanka K; Brook, Mark N; Orr, Nick; Rhie, Suhn Kyong; Riboli, Elio; Feigelson, Heather S; Le Marchand, Loic; Buring, Julie E; Eccles, Diana; Miron, Penelope; Fasching, Peter A; Brauch, Hiltrud; Chang-Claude, Jenny; Carpenter, Jane; Godwin, Andrew K; Nevanlinna, Heli; Giles, Graham G; Cox, Angela; Hopper, John L; Bolla, Manjeet K; Wang, Qin; Dennis, Joe; Dicks, Ed; Howat, Will J; Schoof, Nils; Bojesen, Stig E; Lambrechts, Diether; Broeks, Annegien; Andrulis, Irene L; Guénel, Pascal; Burwinkel, Barbara; Sawyer, Elinor J; Hollestelle, Antoinette; Fletcher, Olivia; Winqvist, Robert; Brenner, Hermann; Mannermaa, Arto; Hamann, Ute; Meindl, Alfons; Lindblom, Annika; Zheng, Wei; Devillee, Peter; Goldberg, Mark S; Lubinski, Jan; Kristensen, Vessela; Swerdlow, Anthony; Anton-Culver, Hoda; Dörk, Thilo; Muir, Kenneth; Matsuo, Keitaro; Wu, Anna H; Radice, Paolo; Teo, Soo Hwang; Shu, Xiao-Ou; Blot, William; Kang, Daehee; Hartman, Mikael; Sangrajrang, Suleeporn; Shen, Chen-Yang; Southey, Melissa C; Park, Daniel J; Hammet, Fleur; Stone, Jennifer; Veer, Laura J Van't; Rutgers, Emiel J; Lophatananon, Artitaya; Stewart-Brown, Sarah; Siriwanarangsan, Pornthep; Peto, Julian; Schrauder, Michael G; Ekici, Arif B; Beckmann, Matthias W; Dos Santos Silva, Isabel; Johnson, Nichola; Warren, Helen; Tomlinson, Ian; Kerin, Michael J; Miller, Nicola; Marme, Federick; Schneeweiss, Andreas; Sohn, Christof; Truong, Therese; Laurent-Puig, Pierre; Kerbrat, Pierre; Nordestgaard, Børge G; Nielsen, Sune F; Flyger, Henrik; Milne, Roger L; Perez, Jose Ignacio Arias; Menéndez, Primitiva; Müller, Heiko; Arndt, Volker; Stegmaier, Christa; Lichtner, Peter; Lochmann, Magdalena; Justenhoven, Christina; Ko, Yon-Dschun; Muranen, Taru A; Aittomäki, Kristiina; Blomqvist, Carl; Greco, Dario; Heikkinen, Tuomas; Ito, Hidemi; Iwata, Hiroji; Yatabe, Yasushi; Antonenkova, Natalia N; Margolin, Sara; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M; Balleine, Rosemary; Tseng, Chiu-Chen; Berg, David Van Den; Stram, Daniel O; Neven, Patrick; Dieudonné, Anne-Sophie; Leunen, Karin; Rudolph, Anja; Nickels, Stefan; Flesch-Janys, Dieter; Peterlongo, Paolo; Peissel, Bernard; Bernard, Loris; Olson, Janet E; Wang, Xianshu; Stevens, Kristen; Severi, Gianluca; Baglietto, Laura; McLean, Catriona; Coetzee, Gerhard A; Feng, Ye; Henderson, Brian E; Schumacher, Fredrick; Bogdanova, Natalia V; Labrèche, France; Dumont, Martine; Yip, Cheng Har; Taib, Nur Aishah Mohd; Cheng, Ching-Yu; Shrubsole, Martha; Long, Jirong; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Kauppila, Saila; Knight, Julia A; Glendon, Gord; Mulligan, Anna Marie; Tollenaar, Robertus A E M; Seynaeve, Caroline M; Kriege, Mieke; Hooning, Maartje J; van den Ouweland, Ans M W; van Deurzen, Carolien H M; Lu, Wei; Gao, Yu-Tang; Cai, Hui; Balasubramanian, Sabapathy P; Cross, Simon S; Reed, Malcolm W R; Signorello, Lisa; Cai, Qiuyin; Shah, Mitul; Miao, Hui; Chan, Ching Wan; Chia, Kee Seng; Jakubowska, Anna; Jaworska, Katarzyna; Durda, Katarzyna; Hsiung, Chia-Ni; Wu, Pei-Ei; Yu, Jyh-Cherng; Ashworth, Alan; Jones, Michael; Tessier, Daniel C; González-Neira, Anna; Pita, Guillermo; Alonso, M Rosario; Vincent, Daniel; Bacot, Francois; Ambrosone, Christine B; Bandera, Elisa V; John, Esther M; Chen, Gary K; Hu, Jennifer J; Rodriguez-Gil, Jorge L; Bernstein, Leslie; Press, Michael F; Ziegler, Regina G; Millikan, Robert M; Deming-Halverson, Sandra L; Nyante, Sarah; Ingles, Sue A; Waisfisz, Quinten; Tsimiklis, Helen; Makalic, Enes; Schmidt, Daniel; Bui, Minh; Gibson, Lorna; Müller-Myhsok, Bertram; Schmutzler, Rita K; Hein, Rebecca; Dahmen, Norbert; Beckmann, Lars; Aaltonen, Kirsimari; Czene, Kamila; Irwanto, Astrid; Liu, Jianjun; Turnbull, Clare; Rahman, Nazneen; Meijers-Heijboer, Hanne; Uitterlinden, Andre G; Rivadeneira, Fernando; Olswold, Curtis; Slager, Susan; Pilarski, Robert; Ademuyiwa, Foluso; Konstantopoulou, Irene; Martin, Nicholas G; Montgomery, Grant W; Slamon, Dennis J; Rauh, Claudia; Lux, Michael P; Jud, Sebastian M; Bruning, Thomas; Weaver, Joellen; Sharma, Priyanka; Pathak, Harsh; Tapper, Will; Gerty, Sue; Durcan, Lorraine; Trichopoulos, Dimitrios; Tumino, Rosario; Peeters, Petra H; Kaaks, Rudolf; Campa, Daniele; Canzian, Federico; Weiderpass, Elisabete; Johansson, Mattias; Khaw, Kay-Tee; Travis, Ruth; Clavel-Chapelon, Françoise; Kolonel, Laurence N; Chen, Constance; Beck, Andy; Hankinson, Susan E; Berg, Christine D; Hoover, Robert N; Lissowska, Jolanta; Figueroa, Jonine D; Chasman, Daniel I; Gaudet, Mia M; Diver, W Ryan; Willett, Walter C; Hunter, David J; Simard, Jacques; Benitez, Javier; Dunning, Alison M; Sherman, Mark E; Chenevix-Trench, Georgia; Chanock, Stephen J; Hall, Per; Pharoah, Paul D P; Vachon, Celine; Easton, Douglas F; Haiman, Christopher A; Kraft, Peter

    2013-04-01

    Estrogen receptor (ER)-negative tumors represent 20-30% of all breast cancers, with a higher proportion occurring in younger women and women of African ancestry. The etiology and clinical behavior of ER-negative tumors are different from those of tumors expressing ER (ER positive), including differences in genetic predisposition. To identify susceptibility loci specific to ER-negative disease, we combined in a meta-analysis 3 genome-wide association studies of 4,193 ER-negative breast cancer cases and 35,194 controls with a series of 40 follow-up studies (6,514 cases and 41,455 controls), genotyped using a custom Illumina array, iCOGS, developed by the Collaborative Oncological Gene-environment Study (COGS). SNPs at four loci, 1q32.1 (MDM4, P = 2.1 × 10(-12) and LGR6, P = 1.4 × 10(-8)), 2p24.1 (P = 4.6 × 10(-8)) and 16q12.2 (FTO, P = 4.0 × 10(-8)), were associated with ER-negative but not ER-positive breast cancer (P > 0.05). These findings provide further evidence for distinct etiological pathways associated with invasive ER-positive and ER-negative breast cancers.

  8. Cordycepin-induced apoptosis and autophagy in breast cancer cells are independent of the estrogen receptor

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Sunga [Department of Physiology, School of Medicine, Chungnam National University, Daejeon, 301747 (Korea, Republic of); Lim, Mi-Hee [Department of Biochemistry, Kangwon National University, Gangwon-do, 200701 (Korea, Republic of); Kim, Ki Mo [Diabetic Complications Research Center, Division of Traditional Korean Medicine (TKM) Integrated Research, Korea Institute of Oriental Medicine (KIOM), 305811, Daejeon (Korea, Republic of); Jeon, Byeong Hwa [Department of Physiology, School of Medicine, Chungnam National University, Daejeon, 301747 (Korea, Republic of); Song, Won O. [Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI 48824 (United States); Kim, Tae Woong, E-mail: tawkim@kangwon.ac.kr [Department of Biochemistry, Kangwon National University, Gangwon-do, 200701 (Korea, Republic of)

    2011-12-15

    Cordycepin (3-deoxyadenosine), found in Cordyceps spp., has been known to have many therapeutic effects including immunomodulatory, anti-inflammatory, antimicrobial, and anti-aging effects. Moreover, anti-tumor and anti-metastatic effects of cordycepin have been reported, but the mechanism causing cancer cell death is poorly characterized. The present study was designed to investigate whether the mechanisms of cordycepin-induced cell death were associated with estrogen receptor in breast cancer cells. Exposure of both MDA-MB-231 and MCF-7 human breast cancer cells to cordycepin resulted in dose-responsive inhibition of cell growth and reduction in cell viability. The cordycepin-induced cell death in MDA-MB-231 cells was associated with several specific features of the mitochondria-mediated apoptotic pathway, which was confirmed by DNA fragmentation, TUNEL, and biochemical assays. Cordycepin also caused a dose-dependent increase in mitochondrial translocation of Bax, triggering cytosolic release of cytochrome c and activation of caspases-9 and -3. Interestingly, MCF-7 cells showed autophagy-associated cell death, as observed by the detection of an autophagosome-specific protein and large membranous vacuole ultrastructure morphology in the cytoplasm. Cordycepin-induced autophagic cell death has applications in treating MCF-7 cells with apoptotic defects, irrespective of the ER response. Although autophagy has a survival function in tumorigenesis of some cancer cells, autophagy may be important for cordycepin-induced MCF-7 cell death. In conclusion, the results of our study demonstrate that cordycepin effectively kills MDA-MB-231 and MCF-7 human breast cancer cell lines in culture. Hence, further studies should be conducted to determine whether cordycepin will be a clinically useful, ER-independent, chemotherapeutic agent for human breast cancer. -- Highlights: Black-Right-Pointing-Pointer We studied the mechanism which cordycepin-induced cell death association with

  9. Association between local inflammation and breast tissue age-related lobular involution among premenopausal and postmenopausal breast cancer patients.

    Directory of Open Access Journals (Sweden)

    Mirette Hanna

    Full Text Available Increased levels of pro-inflammatory markers and decreased levels of anti-inflammatory markers in the breast tissue can result in local inflammation. We aimed to investigate whether local inflammation in the breast tissue is associated with age-related lobular involution, a process inversely related to breast cancer risk. Levels of eleven pro- and anti-inflammatory markers were assessed by immunohistochemistry in normal breast tissue obtained from 164 pre- and postmenopausal breast cancer patients. Involution status of the breast (degree of lobular involution and the predominant lobule type was microscopically assessed in normal breast tissue on hematoxylin-eosin stained mastectomy slides. Multivariate generalized linear models were used to assess the associations. In age-adjusted analyses, higher levels of pro-inflammatory markers IL-6, TNF-α, CRP, COX-2, leptin, SAA1 and IL-8; and anti-inflammatory marker IL-10, were inversely associated with the prevalence of complete lobular involution (all P≤0.04. Higher levels of the pro-inflammatory marker COX-2 were also associated with lower prevalence of predominant type 1/no type 3 lobules in the breast, an indicator of complete involution, in age-adjusted analysis (P = 0.017. Higher tissue levels of inflammatory markers, mainly the pro-inflammatory ones, are associated with less involuted breasts and may consequently be associated with an increased risk of developing breast cancer.

  10. Oxidative stress specifically downregulates survivin to promote breast tumour formation.

    Science.gov (United States)

    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.

  11. Ovarian reserve in breast cancer: assessment with anti-Müllerian hormone.

    Science.gov (United States)

    Hamy, Anne-Sophie; Porcher, Raphaël; Cuvier, Caroline; Giacchetti, Sylvie; Schlageter, Marie-Hélène; Coussieu, Christiane; Gronier, Héloise; Feugeas, Jean-Paul; Adoui, Nadir; Lacorte, Jean-Marc; Poirot, Catherine; Habdous, Mohamed; Espié, Marc

    2014-11-01

    Anti-Müllerian hormone (AMH) levels fall during chemotherapy. Treatment-induced amenorrhoea is a reversible phenomenon, but few data are available on long-term AMH changes in breast cancer. The aim of the study was to describe serum AMH levels before, during and in the long term after chemotherapy, and to show a potential AMH recovery. Between May 2010 and June 2011, we selected 134 women aged 18-43 years at the time of breast cancer diagnosis who received chemotherapy between 2005 and 2011, and had not undergone an oophorectomy or had previous cytotoxic treatment. The AMH levels were assessed before, during and 4 months to 5.5 years after the end of chemotherapy. During chemotherapy, AMH was undetectable in 69% of women. After chemotherapy, a significant increase in AMH was found, with an average magnitude of +1.2% per month (95% credibility interval: 0.7 to 1.6). Older age and 12 months of amenorrhoea were found to be associated with a lower AMH recovery rate, whereas baseline AMH and number of chemotherapy cycles were not. The process of AMH changes during and after chemotherapy is dynamic, and shows recovery after ovarian injury. Caution should be exercised in interpreting individual AMH assessment in this context. Copyright © 2014 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

  12. Retrospective and comparative analysis of 99mTc-Sestamibi breast specific gamma imaging versus mammography, ultrasound, and magnetic resonance imaging for the detection of breast cancer in Chinese women

    International Nuclear Information System (INIS)

    Yu, Xiuyan; Hu, Guoming; Zhang, Zhigang; Qiu, Fuming; Shao, Xuan; Wang, Xiaochen; Zhan, Hongwei; Chen, Yiding; Deng, Yongchuan; Huang, Jian

    2016-01-01

    Diagnosing breast cancer during the early stage may be helpful for decreasing cancer-related mortality. In Western developed countries, mammographies have been the gold standard for breast cancer detection. However, Chinese women usually have denser and smaller-sized breasts compared to Caucasian women, which decreases the diagnostic accuracy of mammography. However, breast specific gamma imaging, a type of molecular functional breast imaging, has been used for the accurate diagnosis of breast cancer and is not influenced by breast density. Our objective was to analyze the breast specific gamma imaging (BSGI) diagnostic value for Chinese women. During a 2-year period, 357 women were diagnosed and treated at our oncology department and received BSGI in addition to mammography (MMG), ultrasound (US) and magnetic resonance imaging (MRI) for diagnostic assessment. We investigated the sensitivity and specificity of each method of detection and compared the biological profiles of the four imaging methods. A total of 357 women received a final surgical pathology diagnosis, with 168 malignant diseases (58.5 %) and 119 benign diseases (41.5 %). Of these, 166 underwent the four imaging tests preoperatively. The sensitivity of BSGI was 80.35 and 82.14 % by US, 75.6 % by MMG, and 94.06 % by MRI. Furthermore, the breast cancer diagnosis specificity of BSGI was high (83.19 % vs. 77.31 % vs. 66.39 % vs. 67.69 %, respectively). The BSGI diagnostic sensitivity for mammographic breast density in women was superior to mammography and more sensitive for non-luminal A subtypes (luminal A vs. non-luminal A, 68.63 % vs. 88.30 %). BSGI may help improve the ability to diagnose early stage breast cancer for Chinese women, particularly for ductal carcinoma in situ (DCIS), mammographic breast density and non-luminal A breast cancer

  13. Retrospective and comparative analysis of (99m)Tc-Sestamibi breast specific gamma imaging versus mammography, ultrasound, and magnetic resonance imaging for the detection of breast cancer in Chinese women.

    Science.gov (United States)

    Yu, Xiuyan; Hu, Guoming; Zhang, Zhigang; Qiu, Fuming; Shao, Xuan; Wang, Xiaochen; Zhan, Hongwei; Chen, Yiding; Deng, Yongchuan; Huang, Jian

    2016-07-11

    Diagnosing breast cancer during the early stage may be helpful for decreasing cancer-related mortality. In Western developed countries, mammographies have been the gold standard for breast cancer detection. However, Chinese women usually have denser and smaller-sized breasts compared to Caucasian women, which decreases the diagnostic accuracy of mammography. However, breast specific gamma imaging, a type of molecular functional breast imaging, has been used for the accurate diagnosis of breast cancer and is not influenced by breast density. Our objective was to analyze the breast specific gamma imaging (BSGI) diagnostic value for Chinese women. During a 2-year period, 357 women were diagnosed and treated at our oncology department and received BSGI in addition to mammography (MMG), ultrasound (US) and magnetic resonance imaging (MRI) for diagnostic assessment. We investigated the sensitivity and specificity of each method of detection and compared the biological profiles of the four imaging methods. A total of 357 women received a final surgical pathology diagnosis, with 168 malignant diseases (58.5 %) and 119 benign diseases (41.5 %). Of these, 166 underwent the four imaging tests preoperatively. The sensitivity of BSGI was 80.35 and 82.14 % by US, 75.6 % by MMG, and 94.06 % by MRI. Furthermore, the breast cancer diagnosis specificity of BSGI was high (83.19 % vs. 77.31 % vs. 66.39 % vs. 67.69 %, respectively). The BSGI diagnostic sensitivity for mammographic breast density in women was superior to mammography and more sensitive for non-luminal A subtypes (luminal A vs. non-luminal A, 68.63 % vs. 88.30 %). BSGI may help improve the ability to diagnose early stage breast cancer for Chinese women, particularly for ductal carcinoma in situ (DCIS), mammographic breast density and non-luminal A breast cancer.

  14. Assessment of the systemic distribution of a bioconjugated anti-Her2 magnetic nanoparticle in a breast cancer model by means of magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Huerta-Núñez, L. F. E., E-mail: lidi-huerta@hotmail.com [Universidad del Ejercito y FAM/EMGS-Laboratorio Multidisciplinario de Investigación (Mexico); Villanueva-Lopez, G. Cleva, E-mail: villanuevacleva3@gmail.com [Instituto Politécnico Nacional-Escuela Superior de Medicina-Sección Investigación y Posgrado (Mexico); Morales-Guadarrama, A., E-mail: amorales@ci3m.mx [Centro Nacional de Investigacion en Imagenologia e Instrumentacion Medica-Universidad Autónoma (Mexico); Soto, S., E-mail: cuadrosdobles@hotmail.com; López, J., E-mail: jaimelocr@hotmail.com; Silva, J. G., E-mail: gabrielsilva173@gmail.com [Universidad del Ejercito y FAM/EMGS-Laboratorio Multidisciplinario de Investigación (Mexico); Perez-Vielma, N., E-mail: nadiampv@gmail.com [Instituto Politécnico Nacional - Centro Interdisciplinario de Ciencias de la Salud Unidad Santo Tomás (CICS-UST) (Mexico); Sacristán, E., E-mail: esacristan@ci3m.mx [Centro Nacional de Investigacion en Imagenologia e Instrumentacion Medica-Universidad Autónoma (Mexico); Gudiño-Zayas, Marco E., E-mail: gudino@unam.mx [UNAM, Departamento de Medicina Experimental, Facultad de Medicina (Mexico); González, C. A., E-mail: cgonzalezd@ipn.mx [Universidad del Ejercito y FAM/EMGS-Laboratorio Multidisciplinario de Investigación (Mexico)

    2016-09-15

    The aim of this study was to determine the systemic distribution of magnetic nanoparticles of 100 nm diameter (MNPs) coupled to a specific monoclonal antibody anti-Her2 in an experimental breast cancer (BC) model. The study was performed in two groups of Sprague–Dawley rats: control (n = 6) and BC chemically induced (n = 3). Bioconjugated “anti-Her2-MNPs” were intravenously administered, and magnetic resonance imaging (MRI) monitored its systemic distribution at seven times after administration. Non-heme iron presence associated with the location of the bioconjugated anti-Her2-MNPs in splenic, hepatic, cardiac and tumor tissues was detected by Perl’s Prussian blue (PPB) stain. Optical density measurements were used to semiquantitatively determine the iron presence in tissues on the basis of a grayscale values integration of T1 and T2 MRI sequence images. The results indicated a delayed systemic distribution of MNPs in cancer compared to healthy conditions with a maximum concentration of MNPs in cancer tissue at 24 h post-infusion.

  15. PARANEOPLASTIC DAMAGE TO THE CENTRAL AND PERIPHERAL NERVOUS SYSTEM IN BREAST CANCER: A CASE REPORT

    Directory of Open Access Journals (Sweden)

    E. S. Koroleva

    2017-01-01

    Full Text Available Paraneoplastic neurological syndrome involves the concurrent development of cancer and neurologicaldiseases. Breast cancer is the second most common cancer associated with paraneoplastic damage to the central and peripheral nervous system. Autoimmune genesis of the disease is characterized by the presence of highly specific onconeural antibodies, which selectively affect neurons in the brain cord, spinal cord and spinal ganglia, and cause the onset of neurological symptoms within 2 years before cancer is detected. Six well-characterized onconeural antibodies detected in the blood serum of breast cancer patients can be used for the laboratory diagnosis of paraneoplastic neurological syndrome. Of them, anti-Hu, anti-CV2 and anti-amphiphysin antibodies cause polyneuropathy most often. Anti-Yo antibody is usually associated with cerebellar degeneration. Multiple neuronal autoantibodies can be simultaneously detected in a patient. Removal of the tumor may lead to stabilization and even partial regression of the neurological symptoms in 70 % of patients. Therefore, the surgical treatment of cancer should consider not only the tumor extension, but also the severity and progression of neurological deficit. We present a case of paraneoplastic cerebellar degeneration and paraneoplastic polyneuropathy in a 50-year-old woman with the neurological symptoms appeared 5 months before breast infiltrating ductal carcinoma was detected. The current approaches to the diagnosis of paraneoplastic neurological syndrome, as well as feasibility of radical removal of the tumor due to progression of neurological deficit were discussed.

  16. Molecular biology of breast cancer stem cells: potential clinical applications.

    Science.gov (United States)

    Nguyen, Nam P; Almeida, Fabio S; Chi, Alex; Nguyen, Ly M; Cohen, Deirdre; Karlsson, Ulf; Vinh-Hung, Vincent

    2010-10-01

    Breast cancer stem cells (CSC) have been postulated recently as responsible for failure of breast cancer treatment. The purpose of this study is to review breast CSCs molecular biology with respect to their mechanism of resistance to conventional therapy, and to develop treatment strategies that may improve survival of breast cancer patients. A literature search has identified in vitro and in vivo studies of breast CSCs. Breast CSCs overexpress breast cancer resistance protein (BCRP) which allows cancer cells to transport actively chemotherapy agents out of the cells. Radioresistance is modulated through activation of Wnt signaling pathway and overexpression of genes coding for glutathione. Lapatinib can selectively target HER-2 positive breast CSCs and improves disease-free survival in these patients. Metformin may target basal type breast CSCs. Parthenolide and oncolytic viruses are promising targeting agents for breast CSCs. Future clinical trials for breast cancer should include anti-cancer stem cells targeting agents in addition to conventional chemotherapy. Hypofractionation radiotherapy may be indicated for residual disease post chemotherapy. 2010 Elsevier Ltd. All rights reserved.

  17. siRNA inhibition of telomerase enhances the anti-cancer effect of doxorubicin in breast cancer cells

    International Nuclear Information System (INIS)

    Dong, Xuejun; Liu, Anding; Zer, Cindy; Feng, Jianguo; Zhen, Zhuan; Yang, Mingfeng; Zhong, Li

    2009-01-01

    Doxorubicin is an effective breast cancer drug but is hampered by a severe, dose-dependent toxicity. Concomitant administration of doxorubicin and another cancer drug may be able to sensitize tumor cells to the cytotoxicity of doxorubicin and lowers the therapeutic dosage. In this study, we examined the combined effect of low-dose doxorubicin and siRNA inhibition of telomerase on breast cancer cells. We found that when used individually, both treatments were rapid and potent apoptosis inducers; and when the two treatments were combined, we observed an enhanced and sustained apoptosis induction in breast cancer cells. siRNA targeting the mRNA of the protein component of telomerase, the telomerase reverse transcriptase (hTERT), was transfected into two breast cancer cell lines. The siRNA inhibition was confirmed by RT-PCR and western blot on hTERT mRNA and protein levels, respectively, and by measuring the activity level of telomerase using the TRAP assay. The effect of the hTERT siRNA on the tumorigenicity of the breast cancer cells was also studied in vivo by injection of the siRNA-transfected breast cancer cells into nude mice. The effects on cell viability, apoptosis and senescence of cells treated with hTERT siRNA, doxorubicin, and the combined treatment of doxorubicin and hTERT siRNA, were examined in vitro by MTT assay, FACS and SA-β-galactosidase staining. The hTERT siRNA effectively knocked down the mRNA and protein levels of hTERT, and reduced the telomerase activity to 30% of the untreated control. In vivo, the tumors induced by the hTERT siRNA-transfected cells were of reduced sizes, indicating that the hTERT siRNA also reduced the tumorigenic potential of the breast cancer cells. The siRNA treatment reduced cell viability by 50% in breast cancer cells within two days after transfection, while 0.5 μM doxorubicin treatment had a comparable effect but with a slower kinetics. The combination of hTERT siRNA and 0.5 μM doxorubicin killed twice as many

  18. Antibody Probes to Estrogen Receptor-Alpha Transcript-Specific Upstream Peptides: Alternate ER-Alpha Promoter Use and Breast Cancer Etiology/Outcome

    National Research Council Canada - National Science Library

    Pentecost, Brian

    2002-01-01

    Positive Estrogen Receptor alpha (ER) status correlates with a reduced incidence of breast cancer recurrence in the first years after resection of tumors, and predicts a favorable response to adjuvant anti-estrogens...

  19. Anti-estrogen Resistance in Human Breast Tumors Is Driven by JAG1-NOTCH4-Dependent Cancer Stem Cell Activity

    Directory of Open Access Journals (Sweden)

    Bruno M. Simões

    2015-09-01

    Full Text Available Breast cancers (BCs typically express estrogen receptors (ERs but frequently exhibit de novo or acquired resistance to hormonal therapies. Here, we show that short-term treatment with the anti-estrogens tamoxifen or fulvestrant decrease cell proliferation but increase BC stem cell (BCSC activity through JAG1-NOTCH4 receptor activation both in patient-derived samples and xenograft (PDX tumors. In support of this mechanism, we demonstrate that high ALDH1 predicts resistance in women treated with tamoxifen and that a NOTCH4/HES/HEY gene signature predicts for a poor response/prognosis in 2 ER+ patient cohorts. Targeting of NOTCH4 reverses the increase in Notch and BCSC activity induced by anti-estrogens. Importantly, in PDX tumors with acquired tamoxifen resistance, NOTCH4 inhibition reduced BCSC activity. Thus, we establish that BCSC and NOTCH4 activities predict both de novo and acquired tamoxifen resistance and that combining endocrine therapy with targeting JAG1-NOTCH4 overcomes resistance in human breast cancers.

  20. iRGD-modified lipid–polymer hybrid nanoparticles loaded with isoliquiritigenin to enhance anti-breast cancer effect and tumor-targeting ability

    Directory of Open Access Journals (Sweden)

    Gao F

    2017-06-01

    Full Text Available Fei Gao,1–3 Jinming Zhang,3 Chaomei Fu,3 Xiaoming Xie,4 Fu Peng,1–3 Jieshu You,1,2 Hailin Tang,1,2,4 Zhiyu Wang,5 Peng Li,6 Jianping Chen1–3 1School of Chinese Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, 2Shenzhen Institute of Research and Innovation, University of Hong Kong, Shenzhen, 3College of Pharmacy, Chengdu University of Chinese Medicine, Chengdu, 4Department of Breast Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 5Department of Mammary Disease, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, 6State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, People’s Republic of China Abstract: Isoliquiritigenin (ISL, a natural anti-breast cancer dietary compound, has poor delivery characteristics and low bioavailability. In order to promote the therapeutic outcome of ISL, a tumor-targeting lipid–polymer hybrid nanoparticle (NP system modified by tumor-homing iRGD peptides has been developed. The hybrid NPs were prepared by a modified single-step nanoprecipitation method to encapsulate ISL. iRGD peptides were anchored on the surface by a postinsertion method (ISL-iRGD NPs. The stable lipid–polymer structure of ISL-iRGD NPs, with high encapsulation and loading efficiency, was confirmed. Compared to free ISL and non-iRGD-modified counterparts, ISL-iRGD NPs showed higher cytotoxicity and cell apoptosis against the different type of breast cancer cells. This was attributable to higher cellular accumulation mediated by the iRGD-integrin recognition and the nanoscale effect. More importantly, based on the active tumor-tissue accumulation by iRGD peptides and the prolonged in vivo circulation by the stealth nanostructure, ISL-iRGD NPs displayed higher tumor-growth inhibition efficiency in 4T1-bearing breast-tumor mouse

  1. Correlation between Duffy blood group phenotype and breast cancer incidence

    International Nuclear Information System (INIS)

    Liu, Xiao-feng; Li, Lian-fang; Ou, Zhou-luo; Shen, Rong; Shao, Zhi-min

    2012-01-01

    Different ethnicities have different distribution of Duffy blood group (DBG) phenotypes and different breast cancer morbidity. A study in our lab demonstrated that Duffy antigen/receptor for chemokines (DARC, also known as DBGP, the Duffy protein phenotype), led to the inhibition of tumorigenesis. Therefore, we tested the hypothesis that DBGP is correlated with breast cancer occurrence. DBGP proteins were examined by indirect antiglobulin testing with anti-FYa and anti-FYb antibodies. The phenotypes were classified into four groups according to the agglutination reactions: FYa + FYb+, FYa + FYb-, FYa-FYb + and FYa-FYb-. The phenotypes and pathological diagnosis of consecutively hospitalized female patients (n = 5,022) suffering from breast cancer at the Shanghai Cancer Hospital and Henan Province Cancer Hospital were investigated. The relationships between DBGP expression with breast cancer occurrence, axillary lymph status, histological subtype, tumor size pathological grade and overall survival were analyzed. The incidence of breast cancer was significantly different between FYa + FYb + (29.8%), FYa + FYb- (33.2%), FYa-FYb + (45.6%) and FYa-FYb- (59.1%; P = 0.001). Significant different numbers of breast cancer patients had metastases to the axillary lymph nodes in the FYa + FYb + group (25.1%), FYa + FYb- (36.9%), FYa-FYb + (41.0%) and FYa-FYb- (50.0%, (P = 0.005). There was a statistical significance (p = 0.022) of the overall survival difference between patients with difference phenotypes. No significant difference was observed in cancer size (t-test, p > 0.05), histological cancer type (Fisher's exact test, p > 0.05) or histological grade (Fisher's exact test, p > 0.05) between every each DBGP group. DBGP is correlated with breast cancer incidence and axillary lymph node metastasis and overall survival. Further investigations are required to determine the underlying mechanism of Duffy blood group phenotype on breast cancer risk

  2. Cytotoxic Effects and Anti-Angiogenesis Potential of Pistachio (Pistacia vera L.) Hulls against MCF-7 Human Breast Cancer Cells.

    Science.gov (United States)

    Seifaddinipour, Maryam; Farghadani, Reyhaneh; Namvar, Farideh; Mohamad, Jamaludin; Abdul Kadir, Habsah

    2018-01-05

    Pistachio ( Pistacia vera L.) hulls (PVLH) represents a significant by-product of industrial pistachio processing that contains high amounta of phenolic and flavonoid compounds known to act as antioxidants. The current study was designed to evaluate the anti-tumor and anti-angiogenic potentials of PVLH extracts. The cytotoxic effects of hexane, ethyl acetate, methanol, and water PVLH extracts toward human colon cancer (HT-29 and HCT-116), breast adenocarcinoma (MCF-7), lung adenocarcinoma (H23), liver hepatocellular carcinoma (HepG2), cervical cancer (Ca Ski), and normal fibroblast (BJ-5ta) cells were assessed using a MTT cell viability assay. Apoptosis induction was evaluated through the different nuclear staining assays and confirmed by flow cytometry analysis. Anti-angiogenic activities were also determined using chorioallantoic membrane (CAM) assay. PVLH ethyl acetate extracts (PVLH-EAE) demonstrated a suppressive effect with an IC 50 value of 21.20 ± 1.35, 23.00 ± 1.2 and 25.15 ± 1.85 µg/mL against MCF-7, HT-29 and HCT-116, respectively, after 72 h of treatment. Morphological assessment and flow cytometry analysis showed the potential of PVLH-EAE to induce apoptosis. PVLH-EAE at the highest concentration demonstrated significant inhibition of angiogenesis as comparing with control group. Also the expression of Bax increased and the expression of Bcl-2 decreased in treated MCF-7 cells. Thus, the apoptosis induction and angiogenesis potential of PVLH-EAE make it to be the most suitable for further cancer research study to deal with selective antitumor active substances to human cancers especially breast cancer.

  3. Dietary Natural Products for Prevention and Treatment of Breast Cancer.

    Science.gov (United States)

    Li, Ya; Li, Sha; Meng, Xiao; Gan, Ren-You; Zhang, Jiao-Jiao; Li, Hua-Bin

    2017-07-08

    Breast cancer is the most common cancer among females worldwide. Several epidemiological studies suggested the inverse correlation between the intake of vegetables and fruits and the incidence of breast cancer. Substantial experimental studies indicated that many dietary natural products could affect the development and progression of breast cancer, such as soy, pomegranate, mangosteen, citrus fruits, apple, grape, mango, cruciferous vegetables, ginger, garlic, black cumin, edible macro-fungi, and cereals. Their anti-breast cancer effects involve various mechanisms of action, such as downregulating ER-α expression and activity, inhibiting proliferation, migration, metastasis and angiogenesis of breast tumor cells, inducing apoptosis and cell cycle arrest, and sensitizing breast tumor cells to radiotherapy and chemotherapy. This review summarizes the potential role of dietary natural products and their major bioactive components in prevention and treatment of breast cancer, and special attention was paid to the mechanisms of action.

  4. Anti-Inflammatory Agent Indomethacin Reduces Invasion and Alters Metabolism in a Human Breast Cancer Cell Line

    Directory of Open Access Journals (Sweden)

    Ellen Ackerstaff

    2007-03-01

    Full Text Available Hostile physiological environments such as hypoxia and acidic extracellular pH, which exist in solid tumors, may promote invasion and metastasis through inflammatory responses and formation of eicosanoids. Here, we have investigated the effects of the antiinflammatory agent indomethacin on the invasion and metabolism of the human breast cancer cell line MDAMB-435 in Dulbecco's Modified Eagles (DME-based or Roswell Park Memorial Institute (RPMI-based cell medium, using a magnetic resonance-compatible invasion assay. Indomethacin treatment significantly reduced the invasion of MDA-MB-435 cells independent of the culture and perfusion conditions examined. Significant changes were detected in levels of intracellular choline phospholipid metabolites and in triglyceride (TG concentrations of these cells, depending on indomethacin treatment and basal cell medium used. Additionally, genetic profiling of breast cancer cells, grown and treated with low-dose indomethacin in cell culture using an RPMI-based medium, revealed the upregulation of several genes implicating cyclooxygenaseindependent targets of indomethacin. These data confirm the ability of an anti-inflammatory agent to reduce breast cancer invasion and demonstrate, depending on cell culture and perfusion conditions, that the indomethacin-induced decrease in invasion is associated with changes in choline phospholipid metabolism, TG metabolism, and gene expression.

  5. Neoadjuvant therapy for early-stage breast cancer: the clinical utility of pertuzumab

    International Nuclear Information System (INIS)

    Gollamudi, Jahnavi; Parvani, Jenny G; Schiemann, William P; Vinayak, Shaveta

    2016-01-01

    Approximately 20% of breast cancer patients harbor tumors that overexpress human epidermal growth factor receptor 2 (HER2; also known as ErbB2), a receptor tyrosine kinase that belongs to the epidermal growth factor receptor family of receptor tyrosine kinases. HER2 amplification and hyperactivation drive the growth and survival of breast cancers through the aberrant activation of proto-oncogenic signaling systems, particularly the Ras/MAP kinase and PI3K/AKT pathways. Although HER2-positive (HER2 + ) breast cancer was originally considered to be a highly aggressive form of the disease, the clinical landscape of HER2 + breast cancers has literally been transformed by the approval of anti-HER2 agents for adjuvant and neoadjuvant settings. Indeed, pertuzumab is a novel monoclonal antibody that functions as an anti-HER2 agent by targeting the extracellular dimerization domain of the HER2 receptor; it is also the first drug to receive an accelerated approval by the US Food and Drug Administration for use in neoadjuvant settings in early-stage HER2 + breast cancer. Here, we review the molecular and cellular factors that contribute to the pathophysiology of HER2 in breast cancer, as well as summarize the landmark preclinical and clinical findings underlying the approval and use of pertuzumab in the neoadjuvant setting. Finally, the molecular mechanisms operant in mediating resistance to anti-HER2 agents, and perhaps to pertuzumab as well, will be discussed, as will the anticipated clinical impact and future directions of pertuzumab in breast cancer patients

  6. Genome-wide association studies identify four ER negative–specific breast cancer risk loci

    Science.gov (United States)

    Garcia-Closas, Montserrat; Couch, Fergus J; Lindstrom, Sara; Michailidou, Kyriaki; Schmidt, Marjanka K; Brook, Mark N; orr, Nick; Rhie, Suhn Kyong; Riboli, Elio; Feigelson, Heather s; Le Marchand, Loic; Buring, Julie E; Eccles, Diana; Miron, Penelope; Fasching, Peter A; Brauch, Hiltrud; Chang-Claude, Jenny; Carpenter, Jane; Godwin, Andrew K; Nevanlinna, Heli; Giles, Graham G; Cox, Angela; Hopper, John L; Bolla, Manjeet K; Wang, Qin; Dennis, Joe; Dicks, Ed; Howat, Will J; Schoof, Nils; Bojesen, Stig E; Lambrechts, Diether; Broeks, Annegien; Andrulis, Irene L; Guénel, Pascal; Burwinkel, Barbara; Sawyer, Elinor J; Hollestelle, Antoinette; Fletcher, Olivia; Winqvist, Robert; Brenner, Hermann; Mannermaa, Arto; Hamann, Ute; Meindl, Alfons; Lindblom, Annika; Zheng, Wei; Devillee, Peter; Goldberg, Mark S; Lubinski, Jan; Kristensen, Vessela; Swerdlow, Anthony; Anton-Culver, Hoda; Dörk, Thilo; Muir, Kenneth; Matsuo, Keitaro; Wu, Anna H; Radice, Paolo; Teo, Soo Hwang; Shu, Xiao-Ou; Blot, William; Kang, Daehee; Hartman, Mikael; Sangrajrang, Suleeporn; Shen, Chen-Yang; Southey, Melissa C; Park, Daniel J; Hammet, Fleur; Stone, Jennifer; Veer, Laura J Van’t; Rutgers, Emiel J; Lophatananon, Artitaya; Stewart-Brown, Sarah; Siriwanarangsan, Pornthep; Peto, Julian; Schrauder, Michael G; Ekici, Arif B; Beckmann, Matthias W; Silva, Isabel dos Santos; Johnson, Nichola; Warren, Helen; Tomlinson, Ian; Kerin, Michael J; Miller, Nicola; Marme, Federick; Schneeweiss, Andreas; Sohn, Christof; Truong, Therese; Laurent-Puig, Pierre; Kerbrat, Pierre; Nordestgaard, Børge G; Nielsen, Sune F; Flyger, Henrik; Milne, Roger L; Perez, Jose Ignacio Arias; Menéndez, Primitiva; Müller, Heiko; Arndt, Volker; Stegmaier, Christa; Lichtner, Peter; Lochmann, Magdalena; Justenhoven, Christina; Ko, Yon-Dschun; Muranen, Taru A; Aittomäki, Kristiina; Blomqvist, Carl; Greco, Dario; Heikkinen, Tuomas; Ito, Hidemi; Iwata, Hiroji; Yatabe, Yasushi; Antonenkova, Natalia N; Margolin, Sara; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M; Balleine, Rosemary; Tseng, Chiu-Chen; Van Den Berg, David; Stram, Daniel O; Neven, Patrick; Dieudonné, Anne-Sophie; Leunen, Karin; Rudolph, Anja; Nickels, Stefan; Flesch-Janys, Dieter; Peterlongo, Paolo; Peissel, Bernard; Bernard, Loris; Olson, Janet E; Wang, Xianshu; Stevens, Kristen; Severi, Gianluca; Baglietto, Laura; Mclean, Catriona; Coetzee, Gerhard A; Feng, Ye; Henderson, Brian E; Schumacher, Fredrick; Bogdanova, Natalia V; Labrèche, France; Dumont, Martine; Yip, Cheng Har; Taib, Nur Aishah Mohd; Cheng, Ching-Yu; Shrubsole, Martha; Long, Jirong; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Kauppila, Saila; knight, Julia A; Glendon, Gord; Mulligan, Anna Marie; Tollenaar, Robertus A E M; Seynaeve, Caroline M; Kriege, Mieke; Hooning, Maartje J; Van den Ouweland, Ans M W; Van Deurzen, Carolien H M; Lu, Wei; Gao, Yu-Tang; Cai, Hui; Balasubramanian, Sabapathy P; Cross, Simon S; Reed, Malcolm W R; Signorello, Lisa; Cai, Qiuyin; Shah, Mitul; Miao, Hui; Chan, Ching Wan; Chia, Kee Seng; Jakubowska, Anna; Jaworska, Katarzyna; Durda, Katarzyna; Hsiung, Chia-Ni; Wu, Pei-Ei; Yu, Jyh-Cherng; Ashworth, Alan; Jones, Michael; Tessier, Daniel C; González-Neira, Anna; Pita, Guillermo; Alonso, M Rosario; Vincent, Daniel; Bacot, Francois; Ambrosone, Christine B; Bandera, Elisa V; John, Esther M; Chen, Gary K; Hu, Jennifer J; Rodriguez-gil, Jorge L; Bernstein, Leslie; Press, Michael F; Ziegler, Regina G; Millikan, Robert M; Deming-Halverson, Sandra L; Nyante, Sarah; Ingles, Sue A; Waisfisz, Quinten; Tsimiklis, Helen; Makalic, Enes; Schmidt, Daniel; Bui, Minh; Gibson, Lorna; Müller-Myhsok, Bertram; Schmutzler, Rita K; Hein, Rebecca; Dahmen, Norbert; Beckmann, Lars; Aaltonen, Kirsimari; Czene, Kamila; Irwanto, Astrid; Liu, Jianjun; Turnbull, Clare; Rahman, Nazneen; Meijers-Heijboer, Hanne; Uitterlinden, Andre G; Rivadeneira, Fernando; Olswold, Curtis; Slager, Susan; Pilarski, Robert; Ademuyiwa, Foluso; Konstantopoulou, Irene; Martin, Nicholas G; Montgomery, Grant W; Slamon, Dennis J; Rauh, Claudia; Lux, Michael P; Jud, Sebastian M; Bruning, Thomas; Weaver, Joellen; Sharma, Priyanka; Pathak, Harsh; Tapper, Will; Gerty, Sue; Durcan, Lorraine; Trichopoulos, Dimitrios; Tumino, Rosario; Peeters, Petra H; Kaaks, Rudolf; Campa, Daniele; Canzian, Federico; Weiderpass, Elisabete; Johansson, Mattias; Khaw, Kay-Tee; Travis, Ruth; Clavel-Chapelon, Françoise; Kolonel, Laurence N; Chen, Constance; Beck, Andy; Hankinson, Susan E; Berg, Christine D; Hoover, Robert N; Lissowska, Jolanta; Figueroa, Jonine D; Chasman, Daniel I; Gaudet, Mia M; Diver, W Ryan; Willett, Walter C; Hunter, David J; Simard, Jacques; Benitez, Javier; Dunning, Alison M; Sherman, Mark E; Chenevix-Trench, Georgia; Chanock, Stephen J; Hall, Per; Pharoah, Paul D P; Vachon, Celine; Easton, Douglas F; Haiman, Christopher A; Kraft, Peter

    2013-01-01

    Estrogen receptor (ER)-negative tumors represent 20–30% of all breast cancers, with a higher proportion occurring in younger women and women of African ancestry1. The etiology2 and clinical behavior3 of ER-negative tumors are different from those of tumors expressing ER (ER positive), including differences in genetic predisposition4. To identify susceptibility loci specific to ER-negative disease, we combined in a meta-analysis 3 genome-wide association studies of 4,193 ER-negative breast cancer cases and 35,194 controls with a series of 40 follow-up studies (6,514 cases and 41,455 controls), genotyped using a custom Illumina array, iCOGS, developed by the Collaborative Oncological Gene-environment Study (COGS). SNPs at four loci, 1q32.1 (MDM4, P = 2.1 × 10−12 and LGR6, P = 1.4 × 10−8), 2p24.1 (P = 4.6 × 10−8) and 16q12.2 (FTO, P = 4.0 × 10−8), were associated with ER-negative but not ER-positive breast cancer (P > 0.05). These findings provide further evidence for distinct etiological pathways associated with invasive ER-positive and ER-negative breast cancers. PMID:23535733

  7. Is breast compression associated with breast cancer detection and other early performance measures in a population-based breast cancer screening program?

    Science.gov (United States)

    Moshina, Nataliia; Sebuødegård, Sofie; Hofvind, Solveig

    2017-06-01

    We aimed to investigate early performance measures in a population-based breast cancer screening program stratified by compression force and pressure at the time of mammographic screening examination. Early performance measures included recall rate, rates of screen-detected and interval breast cancers, positive predictive value of recall (PPV), sensitivity, specificity, and histopathologic characteristics of screen-detected and interval breast cancers. Information on 261,641 mammographic examinations from 93,444 subsequently screened women was used for analyses. The study period was 2007-2015. Compression force and pressure were categorized using tertiles as low, medium, or high. χ 2 test, t tests, and test for trend were used to examine differences between early performance measures across categories of compression force and pressure. We applied generalized estimating equations to identify the odds ratios (OR) of screen-detected or interval breast cancer associated with compression force and pressure, adjusting for fibroglandular and/or breast volume and age. The recall rate decreased, while PPV and specificity increased with increasing compression force (p for trend screen-detected cancer, PPV, sensitivity, and specificity decreased with increasing compression pressure (p for trend breast cancer compared with low compression pressure (1.89; 95% CI 1.43-2.48). High compression force and low compression pressure were associated with more favorable early performance measures in the screening program.

  8. Chemotherapeutic potential of diazeniumdiolate-based aspirin prodrugs in breast cancer.

    Science.gov (United States)

    Basudhar, Debashree; Cheng, Robert C; Bharadwaj, Gaurav; Ridnour, Lisa A; Wink, David A; Miranda, Katrina M

    2015-06-01

    Diazeniumdiolate-based aspirin prodrugs have previously been shown to retain the anti-inflammatory properties of aspirin while protecting against the common side effect of stomach ulceration. Initial analysis of two new prodrugs of aspirin that also release either nitroxyl (HNO) or nitric oxide (NO) demonstrated increased cytotoxicity toward human lung carcinoma cells compared to either aspirin or the parent nitrogen oxide donor. In addition, cytotoxicity was significantly lower in endothelial cells, suggesting cancer-specific sensitivity. To assess the chemotherapeutic potential of these new prodrugs in treatment of breast cancer, we studied their effect both in cultured cells and in a nude mouse model. Both prodrugs reduced growth of breast adenocarcinoma cells more effectively than the parent compounds while not being appreciably cytotoxic in a related nontumorigenic cell line (MCF-10A). The HNO donor also was more cytotoxic than the related NO donor. The basis for the observed specificity was investigated in terms of impact on metabolism, DNA damage and repair, apoptosis, angiogenesis and metastasis. The results suggest a significant pharmacological potential for treatment of breast cancer. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Silencing MED1 sensitizes breast cancer cells to pure anti-estrogen fulvestrant in vitro and in vivo.

    Directory of Open Access Journals (Sweden)

    Lijiang Zhang

    Full Text Available Pure anti-estrogen fulvestrant has been shown to be a promising ER antagonist for locally advanced and metastatic breast cancer. Unfortunately, a significant proportion of patients developed resistance to this type of endocrine therapy but the molecular mechanisms governing cellular responsiveness to this agent remain poorly understood. Here, we've reported that knockdown of estrogen receptor coactivator MED1 sensitized fulvestrant resistance breast cancer cells to fulvestrant treatment. We found that MED1 knockdown further promoted cell cycle arrest induced by fulvestrant. Using an orthotopic xenograft mouse model, we found that knockdown of MED1 significantly reduced tumor growth in mice. Importantly, knockdown of MED1 further potentiated tumor growth inhibition by fulvestrant. Mechanistic studies indicated that combination of fulvestrant treatment and MED1 knockdown is able to cooperatively inhibit the expression of ER target genes. Chromatin immunoprecipitation experiments further supported a role for MED1 in regulating the recruitment of RNA polymerase II and transcriptional corepressor HDAC1 on endogenous ER target gene promoter in the presence of fulvestrant. These results demonstrate a role for MED1 in mediating resistance to the pure anti-estrogen fulvestrant both in vitro and in vivo.

  10. Clodronate Therapy in Patients with Breast Cancer and Bone Metastases

    International Nuclear Information System (INIS)

    Saber, M.M.; Shouman, T.

    2003-01-01

    To assess whether clodronate can reduce frequency of skeletal morbidity in women with lytic bone metastases from breast cancer. Methods: Between 1997 and 2001,167 patients with stage IV breast cancer with bone metastases, were randomly assigned to receive clodronate at a dose of 1600 mg per day orally for 12 months, in addition to the standard specific anti cancer therapy (87 patients) or standard anti cancer therapy only (80 patients). Skeletal complications, including pathological fractures, the need for radiation to bone or bone surgery, spinal cord compression and hypercalcaemia (a serum calcium concentration above 12 mg per deci liter (3.0 mmol per liter) or elevated to any degree and requiring treatment) were assessed monthly. Bone pam. use of analgesic drugs, performance status and quality of life were assessed throughout the trial. Results: There was no significant difference between the two groups at study entry regarding clinical characteristics. The median time for first skeletal complication was ,significantly less in the control group (6.1 vs 9.7 months, ρ=0.05). The proportion of patients who had any skeletal complication in the clodronate group than the control group, but the difference was insignificant (ρ 0.09). Clodronate was generally well tolerated and the main side effects were constipation (32%) flatulence/dyspepsia (17%) and anorexia (8%). The overall survival was not affected by clodronate therapy. The median survival was 14 months In the clodronate group and 13.8 months in the control group. Conclusions: Clodronate is an effective supplement to conventional anticancer treatment for breast cancer with bone metastasis. It reduces skeletal complications and relieves symptoms associated with lytic bone lesions. Further clinical trials that recruit a larger number of patients will be needed to clearly define the role of clodronate in metastatic breast cancer

  11. Anti-human CD73 monoclonal antibody inhibits metastasis formation in human breast cancer by inducing clustering and internalization of CD73 expressed on the surface of cancer cells

    DEFF Research Database (Denmark)

    Terp, Mikkel G; Olesen, Kristina A; Christensen, Eva Arnspang

    2013-01-01

    -linking of CD73, because both whole IgG anti-CD73 AD2 mAb and Fab' fragments thereof exhibited this effect. Ex vivo treatment of different breast cancer cell lines with anti-CD73 AD2 mAb before i.v. injection into mice inhibited extravasation/colonization of circulating tumor cells and significantly reduced...

  12. A novel imidazopyridine analogue as a phosphatidylinositol 3-kinase inhibitor against human breast cancer.

    Science.gov (United States)

    Lee, Hyunseung; Li, Guang-Yong; Jeong, Yujeong; Jung, Kyung Hee; Lee, Ju-Hee; Ham, Kyungrok; Hong, Sungwoo; Hong, Soon-Sun

    2012-05-01

    Potentiation of anti-breast cancer activity of an imidazopyridine-based PI3Kα inhibitor, HS-104, was investigated in human breast cancer cells. HS-104 shows strong inhibitory activity against recombinant PI3Kα isoform and the PI3K signaling pathway, resulting in anti-proliferative activity in breast cancer cells. It also induced cell cycle arrest at the G(2)/M phase as well as apoptosis. Furthermore, oral administration of HS-104 significantly inhibited the growth of tumor in SkBr3 mouse xenograft models. Therefore, HS-104 could be considered as a potential candidate for the treatment of human breast cancer. Crown Copyright © 2011. Published by Elsevier Ireland Ltd. All rights reserved.

  13. Regular and low-dose aspirin, other non-steroidal anti-inflammatory medications and prospective risk of HER2-defined breast cancer: the California Teachers Study.

    Science.gov (United States)

    Clarke, Christina A; Canchola, Alison J; Moy, Lisa M; Neuhausen, Susan L; Chung, Nadia T; Lacey, James V; Bernstein, Leslie

    2017-05-01

    Regular users of aspirin may have reduced risk of breast cancer. Few studies have addressed whether risk reduction pertains to specific breast cancer subtypes defined jointly by hormone receptor (estrogen and progesterone receptor) and human epidermal growth factor receptor 2 (HER2) expression. This study assessed the prospective risk of breast cancer (overall and by subtype) according to use of aspirin and other non-steroidal anti-inflammatory medications (NSAIDs) in a cohort of female public school professionals in California. In 1995 - 1996, participants in the California Teachers Study completed a baseline questionnaire on family history of cancer and other conditions, use of NSAIDs, menstrual and reproductive history, self-reported weight and height, living environment, diet, alcohol use, and physical activity. In 2005-2006, 57,164 participants provided some updated information, including use of NSAIDs and 1457 of these participants developed invasive breast cancer before January 2013. Multivariable Cox proportional hazards regression models provided hazard rate ratios (HRR) for the association between NSAID use and risk of invasive breast cancer as well as hormone receptor- and HER2-defined subtypes. Developing breast cancer was associated inversely with taking three or more tablets of low-dose aspirin per week (23% of participants). Among women reporting this exposure, the HRR was 0.84 (95% confidence interval (CI) 0.72-0.98) compared to those not taking NSAIDs and this was particularly evident in women with the hormone receptor-positive/HER2-negative subtype (HRR = 0.80, 95% CI 0.66-0.96). Use of three or more tablets of "other" NSAIDs was marginally associated with lower risk of breast cancer (HRR = 0.79, 95% CI 0.62-1.00). Other associations with NSAIDs were generally null. Our observation of reduced risk of breast cancer, among participants who took three or more tablets of low-dose aspirin weekly, is consistent with other reports looking at

  14. Emerging treatments for HER2-positive early-stage breast cancer: focus on neratinib.

    Science.gov (United States)

    Kourie, Hampig Raphael; El Rassy, Elie; Clatot, Florian; de Azambuja, Evandro; Lambertini, Matteo

    2017-01-01

    Over the last decades, a better understanding of breast cancer heterogeneity provided tools for a biologically based personalization of anticancer treatments. In particular, the overexpression of the human epidermal growth factor receptor 2 (HER2) by tumor cells provided a specific target in these HER2-positive tumors. The development of the monoclonal antibody trastuzumab, and its approval in 1998 for the treatment of patients with metastatic disease, radically changed the natural history of this aggressive subtype of breast cancer. These findings provided strong support for the continuous research in targeting the HER2 pathway and implementing the development of new anti-HER2 targeted agents. Besides trastuzumab, a series of other anti-HER2 agents have been developed and are currently being explored for the treatment of breast cancer patients, including those diagnosed with early-stage disease. Among these agents, neratinib, an oral tyrosine kinase inhibitor that irreversibly inhibits HER1, HER2, and HER4 at the intracellular level, has shown promising results, including when administered to patients previously exposed to trastuzumab-based treatment. This article aims to review the available data on the role of the HER2 pathway in breast cancer and on the different targeted agents that have been studied or are currently under development for the treatment of patients with early-stage HER2-positive disease with a particular focus on neratinib.

  15. Breast cancer epidemiology and risk factors

    International Nuclear Information System (INIS)

    Broeders, M. J. M.; Verbeek, A. L. M.

    1997-01-01

    Breast cancer is the most common malignancy among women in the Western society. Over the past decades it has become apparent that breast cancer incidence rates are increasing steadily, whereas the mortality rates for breast cancer have remained relatively constant. Information through the media on this rising number of cases has increased breast health awareness but has also introduced anxiety in the female population. This combination of factors has made the need for prevention of breast cancer an urgent matter. Breast cancer does not seem to be a single disease entity. A specific etiologic factor may therefore have more influence on one form may therefore have more influence on one form of breast cancer than another. So far though, as shown in their summary of current knowledge on established and dubious risk factors, no risk factors have been identified that can explain a major part of the incidence. Efforts to identify other ways for primary prevention have also been discouraging, even though breast cancer is one of the most investigated tumours world-wide. Thus, at this point i time, the most important strategy to reduce breast cancer mortality is early detection through individual counselling and organised breast screening programs. The recent isolation of breast cancer susceptibility genes may introduce new ways to reduce the risk of breast cancer in a small subset of women

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

  18. Specific CDK4/6 inhibition in breast cancer

    DEFF Research Database (Denmark)

    Polk, Anne; Kolmos, Ida Lykke; Kümler, Iben

    2016-01-01

    BACKGROUND: Loss of cell cycle control is a hallmark of cancer, and aberrations in the cyclin-dependent kinase-retinoblastoma (CDK-Rb) pathway are common in breast cancer (BC). Consequently, inhibition of this pathway is an attractive therapeutic strategy. The present review addresses efficacy...

  19. Emerging treatments for HER2-positive early-stage breast cancer: focus on neratinib

    Directory of Open Access Journals (Sweden)

    Kourie HR

    2017-07-01

    Full Text Available Hampig Raphael Kourie,1 Elie El Rassy,1 Florian Clatot,2,3 Evandro de Azambuja,4 Matteo Lambertini3,4 1Department of Oncology, Faculty of Medicine, Saint Joseph University, Beirut, Lebanon; 2Department of Medical Oncology and IRON/U1245, Centre Henri Becquerel, Rouen, France; 3Breast Cancer Translational Research Laboratory, 4Department of Medicine, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium Abstract: Over the last decades, a better understanding of breast cancer heterogeneity provided tools for a biologically based personalization of anticancer treatments. In particular, the overexpression of the human epidermal growth factor receptor 2 (HER2 by tumor cells provided a specific target in these HER2-positive tumors. The development of the monoclonal antibody trastuzumab, and its approval in 1998 for the treatment of patients with metastatic disease, radically changed the natural history of this aggressive subtype of breast cancer. These findings provided strong support for the continuous research in targeting the HER2 pathway and implementing the development of new anti-HER2 targeted agents. Besides trastuzumab, a series of other anti-HER2 agents have been developed and are currently being explored for the treatment of breast cancer patients, including those diagnosed with early-stage disease. Among these agents, neratinib, an oral tyrosine kinase inhibitor that irreversibly inhibits HER1, HER2, and HER4 at the intracellular level, has shown promising results, including when administered to patients previously exposed to trastuzumab-based treatment. This article aims to review the available data on the role of the HER2 pathway in breast cancer and on the different targeted agents that have been studied or are currently under development for the treatment of patients with early-stage HER2-positive disease with a particular focus on neratinib. Keywords: breast cancer, HER2-positive, neratinib, early-stage, targeted

  20. Knockdown of dual specificity phosphatase 4 enhances the chemosensitivity of MCF-7 and MCF-7/ADR breast cancer cells to doxorubicin

    International Nuclear Information System (INIS)

    Liu, Yu; Du, Feiya; Chen, Wei; Yao, Minya; Lv, Kezhen; Fu, Peifen

    2013-01-01

    Background: Breast cancer is the major cause of cancer-related deaths in females world-wide. Doxorubicin-based therapy has limited efficacy in breast cancer due to drug resistance, which has been shown to be associated with the epithelial-to-mesenchymal transition (EMT). However, the molecular mechanisms linking the EMT and drug resistance in breast cancer cells remain unclear. Dual specificity phosphatase 4 (DUSP4), a member of the dual specificity phosphatase family, is associated with cellular proliferation and differentiation; however, its role in breast cancer progression is controversial. Methods: We used cell viability assays, Western blotting and immunofluorescent staining, combined with siRNA interference, to evaluate chemoresistance and the EMT in MCF-7 and adriamycin-resistant MCF-7/ADR breast cancer cells, and investigate the underlying mechanisms. Results: Knockdown of DUSP4 significantly increased the chemosensitivity of MCF-7 and MCF-7/ADR breast cancer cells to doxorubicin, and MCF-7/ADR cells which expressed high levels of DUSP4 had a mesenchymal phenotype. Furthermore, knockdown of DUSP4 reversed the EMT in MCF-7/ADR cells, as demonstrated by upregulation of epithelial biomarkers and downregulation of mesenchymal biomarkers, and also increased the chemosensitivity of MCF-7/ADR cells to doxorubicin. Conclusions: DUSP4 might represent a potential drug target for inhibiting drug resistance and regulating the process of the EMT during the treatment of breast cancer. - Highlights: • We used different technologies to prove our conclusion. • DUSP4 knockdown increased doxorubicin chemosensitivity in breast cancer cells. • DUSP4 is a potential target for combating drug resistance in breast cancer. • DUSP4 is a potential target for regulating the EMT in breast cancer

  1. Rhein Induces Apoptosis in Human Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Ching-Yao Chang

    2012-01-01

    Full Text Available Human breast cancers cells overexpressing HER2/neu are more aggressive tumors with poor prognosis, and resistance to chemotherapy. This study investigates antiproliferation effects of anthraquinone derivatives of rhubarb root on human breast cancer cells. Of 7 anthraquinone derivatives, only rhein showed antiproliferative and apoptotic effects on both HER2-overexpressing MCF-7 (MCF-7/HER2 and control vector MCF-7 (MCF-7/VEC cells. Rhein induced dose- and time-dependent manners increase in caspase-9-mediated apoptosis correlating with activation of ROS-mediated activation of NF-κB- and p53-signaling pathways in both cell types. Therefore, this study highlighted rhein as processing anti-proliferative activity against HER2 overexpression or HER2-basal expression in breast cancer cells and playing important roles in apoptotic induction of human breast cancer cells.

  2. Leptin/HER2 crosstalk in breast cancer: in vitro study and preliminary in vivo analysis

    International Nuclear Information System (INIS)

    Fiorio, Elena; Bonetti, Franco; Giordano, Antonio; Cetto, Gian Luigi; Surmacz, Eva; Mercanti, Anna; Terrasi, Marianna; Micciolo, Rocco; Remo, Andrea; Auriemma, Alessandra; Molino, Annamaria; Parolin, Veronica; Di Stefano, Bruno

    2008-01-01

    Obesity in postmenopausal women is associated with increased breast cancer risk, development of more aggressive tumors and resistance to certain anti-breast cancer treatments. Some of these effects might be mediated by obesity hormone leptin, acting independently or modulating other signaling pathways. Here we focused on the link between leptin and HER2. We tested if HER2 and the leptin receptor (ObR) can be coexpressed in breast cancer cell models, whether these two receptors can physically interact, and whether leptin can transactivate HER2. Next, we studied if leptin/ObR can coexist with HER2 in breast cancer tissues, and if presence of these two systems correlates with specific clinicopathological features. Expression of ObR, HER2, phospo-HER2 was assessed by immonoblotting. Physical interactions between ObR and HER2 were probed by immunoprecipitation and fluorescent immunostaining. Expression of leptin and ObR in breast cancer tissues was detected by immunohistochemistry (IHC). Associations among markers studied by IHC were evaluated using Fisher's exact test for count data. HER2 and ObR were coexpressed in all studied breast cancer cell lines. In MCF-7 cells, HER2 physically interacted with ObR and leptin treatment increased HER2 phosphorylation on Tyr 1248. In 59 breast cancers, the presence of leptin was correlated with ObR (the overall association was about 93%). This result was confirmed both in HER2-positive and in HER2-negative subgroups. The expression of leptin or ObR was numerically more frequent in larger (> 10 mm) tumors. Coexpression of HER2 and the leptin/ObR system might contribute to enhanced HER2 activity and reduced sensitivity to anti-HER2 treatments

  3. Anti-tumor effects of Ganoderma lucidum (reishi in inflammatory breast cancer in in vivo and in vitro models.

    Directory of Open Access Journals (Sweden)

    Ivette J Suarez-Arroyo

    Full Text Available The medicinal mushroom Ganoderma lucidum (Reishi was tested as a potential therapeutic for Inflammatory Breast Cancer (IBC using in vivo and in vitro IBC models. IBC is a lethal and aggressive form of breast cancer that manifests itself without a typical tumor mass. Studies show that IBC tissue biopsies overexpress E-cadherin and the eukaryotic initiation factor 4GI (eIF4GI, two proteins that are partially responsible for the unique pathological properties of this disease. IBC is treated with a multimodal approach that includes non-targeted systemic chemotherapy, surgery, and radiation. Because of its non-toxic and selective anti-cancer activity, medicinal mushroom extracts have received attention for their use in cancer therapy. Our previous studies demonstrate these selective anti-cancer effects of Reishi, where IBC cell viability and invasion, as well as the expression of key IBC molecules, including eIF4G is compromised. Thus, herein we define the mechanistic effects of Reishi focusing on the phosphoinositide-3-kinase (PI3K/AKT/mammalian target of rapamycin (mTOR pathway, a regulator of cell survival and growth. The present study demonstrates that Reishi treated IBC SUM-149 cells have reduced expression of mTOR downstream effectors at early treatment times, as we observe reduced eIF4G levels coupled with increased levels of eIF4E bound to 4E-BP, with consequential protein synthesis reduction. Severe combined immunodeficient mice injected with IBC cells treated with Reishi for 13 weeks show reduced tumor growth and weight by ∼50%, and Reishi treated tumors showed reduced expression of E-cadherin, mTOR, eIF4G, and p70S6K, and activity of extracellular regulated kinase (ERK1/2. Our results provide evidence that Reishi suppresses protein synthesis and tumor growth by affecting survival and proliferative signaling pathways that act on translation, suggesting that Reishi is a potential natural therapeutic for breast and other cancers.

  4. Mammography combined with breast dynamic contrast-enhanced-magnetic resonance imaging for the diagnosis of early breast cancer

    Institute of Scientific and Technical Information of China (English)

    Yakun He; Guohui Xu; Jin Ren; Bin Feng; Xiaolei Dong; Hao Lu; Changjiu He

    2016-01-01

    Objective The aim of this study was to investigate the application of mammography combined with breast dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for the diagnosis of early breast cancer. Methods Mammography and DCE-MRI were performed for 120 patients with breast cancer (malignant, 102; benign; 18). Results The sensitivity of mammography for early diagnosis of breast cancer was 66.67%, specificity was 77.78%, and accuracy was 68.33%. The sensitivity of MRI for early diagnosis of breast cancer was 94.12%, specificity was 88.89%, and accuracy was 93.33%. However, the sensitivity of mammography combined with DCE-MRI volume imaging with enhanced water signal (VIEWS) scanning for early diagnosis of breast cancer was 97.06%, specificity was 94.44%, and accuracy was 96.67%. Conclusion Mammography combined with DCE-MRI increased the sensitivity, specificity, and accuracy of diagnosing early breast cancer.

  5. Human Papilloma Viruses and Breast Cancer - Assessment of Causality.

    Science.gov (United States)

    Lawson, James Sutherland; Glenn, Wendy K; Whitaker, Noel James

    2016-01-01

    High risk human papilloma viruses (HPVs) may have a causal role in some breast cancers. Case-control studies, conducted in many different countries, consistently indicate that HPVs are more frequently present in breast cancers as compared to benign breast and normal breast controls (odds ratio 4.02). The assessment of causality of HPVs in breast cancer is difficult because (i) the HPV viral load is extremely low, (ii) HPV infections are common but HPV associated breast cancers are uncommon, and (iii) HPV infections may precede the development of breast and other cancers by years or even decades. Further, HPV oncogenesis can be indirect. Despite these difficulties, the emergence of new evidence has made the assessment of HPV causality, in breast cancer, a practical proposition. With one exception, the evidence meets all the conventional criteria for a causal role of HPVs in breast cancer. The exception is "specificity." HPVs are ubiquitous, which is the exact opposite of specificity. An additional reservation is that the prevalence of breast cancer is not increased in immunocompromised patients as is the case with respect to HPV-associated cervical cancer. This indicates that HPVs may have an indirect causal influence in breast cancer. Based on the overall evidence, high-risk HPVs may have a causal role in some breast cancers.

  6. Body mass index and breast cancer survival

    DEFF Research Database (Denmark)

    Guo, Qi; Burgess, Stephen; Turman, Constance

    2017-01-01

    Background: There is increasing evidence that elevated body mass index (BMI) is associated with reduced survival for women with breast cancer. However, the underlying reasons remain unclear. We conducted a Mendelian randomization analysis to investigate a possible causal role of BMI in survival...... from breast cancer. Methods: We used individual-level data from six large breast cancer case-cohorts including a total of 36 210 individuals (2475 events) of European ancestry. We created a BMI genetic risk score (GRS) based on genotypes at 94 known BMI-associated genetic variants. Association between...... the BMI genetic score and breast cancer survival was analysed by Cox regression for each study separately. Study-specific hazard ratios were pooled using fixed-effect meta-analysis. Results: BMI genetic score was found to be associated with reduced breast cancer-specific survival for estrogen receptor (ER...

  7. Breast Cancer Prevention

    Science.gov (United States)

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

  8. Breast Cancer Treatment

    Science.gov (United States)

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

  9. Transforming growth factor β-activated kinase 1 inhibitor suppresses the proliferation in triple-negative breast cancer through TGF-β/TGFR pathway.

    Science.gov (United States)

    Zhang, Liangyu; Fu, Zelong; Li, Xia; Tang, Haitao; Luo, Jiesi; Zhang, Dehui; Zhuang, Yongzhi; Han, Zhiyang; Yin, Mingzhu

    2017-09-01

    Breast cancer is one of the most invasive cancer types in female population. The functional activity of Transforming growth factor β-activated kinase 1 (TAK1) in breast cancer progression increasingly attracts attention as it provides a potential target for antibreast cancer drug development. However, the fundamental role of TAK1 for triple-negative breast cancer (TNBC) progression and the effect of potential anti-TAK1 drug candidate needs to be further evaluated. Herein, we focused on the role of TAK1 in human breast cancer cells, and we hypothesized that the inhibition of TAK1 activation can repress the growth of human TNBC cells. We found that the TAK1 is robustly activated within cancer cell population of clinic-derived TNBC samples and the human breast cancer cell lines in culture. Furthermore, we determined the effect of 5Z-7-oxozeaenol (5Z-O), a TAK1-specific small molecule inhibitor, on proliferation of human TNBC cell line. 5Z-O treatment significantly suppressed the proliferation of human TNBC cells. Collectively, these demonstrate the role of TAK1 in human breast cancer and the antiproliferate effect of TAK1 inhibitor. Our study sets the stage for further research on TAK1 as a promising target for development of anti-TNBC drugs and therapeutic strategies. © 2017 John Wiley & Sons A/S.

  10. Neoadjuvant therapy for early-stage breast cancer: the clinical utility of pertuzumab

    Directory of Open Access Journals (Sweden)

    Gollamudi J

    2016-02-01

    Full Text Available Jahnavi Gollamudi,1,* Jenny G Parvani,2,* William P Schiemann,3 Shaveta Vinayak3,4 1Department of Internal Medicine, 2Department of Biomedical Engineering, 3Case Comprehensive Cancer Center, Case Western Reserve University, 4Department of Hematology and Oncology, University Hospitals Case Medical Center, Cleveland, OH, USA *These authors contributed equally to this work Abstract: Approximately 20% of breast cancer patients harbor tumors that overexpress human epidermal growth factor receptor 2 (HER2; also known as ErbB2, a receptor tyrosine kinase that belongs to the epidermal growth factor receptor family of receptor tyrosine kinases. HER2 amplification and hyperactivation drive the growth and survival of breast cancers through the aberrant activation of proto-oncogenic signaling systems, particularly the Ras/MAP kinase and PI3K/AKT pathways. Although HER2-positive (HER2+ breast cancer was originally considered to be a highly aggressive form of the disease, the clinical landscape of HER2+ breast cancers has literally been transformed by the approval of anti-HER2 agents for adjuvant and neoadjuvant settings. Indeed, pertuzumab is a novel monoclonal antibody that functions as an anti-HER2 agent by targeting the extracellular dimerization domain of the HER2 receptor; it is also the first drug to receive an accelerated approval by the US Food and Drug Administration for use in neoadjuvant settings in early-stage HER2+ breast cancer. Here, we review the molecular and cellular factors that contribute to the pathophysiology of HER2 in breast cancer, as well as summarize the landmark preclinical and clinical findings underlying the approval and use of pertuzumab in the neoadjuvant setting. Finally, the molecular mechanisms operant in mediating resistance to anti-HER2 agents, and perhaps to pertuzumab as well, will be discussed, as will the anticipated clinical impact and future directions of pertuzumab in breast cancer patients. Keywords: breast cancer

  11. Anti-Ma2 antibody related paraneoplastic limbic/brain stem encephalitis associated with breast cancer expressing Ma1, Ma2, and Ma3 mRNAs.

    Science.gov (United States)

    Sahashi, K; Sakai, K; Mano, K; Hirose, G

    2003-09-01

    A 69 year old woman presented with cognitive impairment and supranuclear gaze palsy caused by paraneoplastic limbic/brain stem encephalitis associated with atypical medullary breast carcinoma. The cerebrospinal fluid from the patient harboured an anti-neuronal cell antibody against Ma2 antigen, but not against Ma1 or Ma3 antigen. Despite the antibody being restricted to the Ma2 antigen, the patient's cancer tissue expressed Ma1, Ma2, and Ma3 mRNAs. These results, and the expression of Ma2 mRNA in an atypical medullar breast carcinoma in another patient without paraneoplastic encephalitis, indicate that the induction of anti-Ma2 antibody depends on host immunoreponsiveness and not on the presence of the antigen itself in the cancer.

  12. Breast cancer screening

    Science.gov (United States)

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

  13. Largazole as a Novel and Selective Anti-Breast Cancer Agent. Addendum

    Science.gov (United States)

    2013-12-01

    HDAC, xenograft, 3D culture, SAR, triple-negative breast cancer Major Objectives and Activities Three specific aims were proposed in the original...polyethylenimine-modified cellulose plates (J.T. Baker, Phillipsburg, NJ) and developed in filtered 0.34 M potassium phosphate pH 7.0 for 20 minutes in...a glass jar. The TLC plates were allowed to air dry for 10 minutes, covered in plastic wrap, and then exposed to a phosphoimager plate for 5– 10

  14. Anti-HER2 IgY antibody-functionalized single-walled carbon nanotubes for detection and selective destruction of breast cancer cells

    Directory of Open Access Journals (Sweden)

    Mitra Somenath

    2009-10-01

    Full Text Available Abstract Background Nanocarrier-based antibody targeting is a promising modality in therapeutic and diagnostic oncology. Single-walled carbon nanotubes (SWNTs exhibit two unique optical properties that can be exploited for these applications, strong Raman signal for cancer cell detection and near-infrared (NIR absorbance for selective photothermal ablation of tumors. In the present study, we constructed a HER2 IgY-SWNT complex and demonstrated its dual functionality for both detection and selective destruction of cancer cells in an in vitro model consisting of HER2-expressing SK-BR-3 cells and HER2-negative MCF-7 cells. Methods The complex was constructed by covalently conjugating carboxylated SWNTs with anti-HER2 chicken IgY antibody, which is more specific and sensitive than mammalian IgGs. Raman signals were recorded on Raman spectrometers with a laser excitation at 785 nm. NIR irradiation was performed using a diode laser system, and cells with or without nanotube treatment were irradiated by 808 nm laser at 5 W/cm2 for 2 min. Cell viability was examined by the calcein AM/ethidium homodimer-1 (EthD-1 staining. Results Using a Raman optical microscope, we found the Raman signal collected at single-cell level from the complex-treated SK-BR-3 cells was significantly greater than that from various control cells. NIR irradiation selectively destroyed the complex-targeted breast cancer cells without harming receptor-free cells. The cell death was effectuated without the need of internalization of SWNTs by the cancer cells, a finding that has not been reported previously. Conclusion We have demonstrated that the HER2 IgY-SWNT complex specifically targeted HER2-expressing SK-BR-3 cells but not receptor-negative MCF-7 cells. The complex can be potentially used for both detection and selective photothermal ablation of receptor-positive breast cancer cells without the need of internalization by the cells. Thus, the unique intrinsic properties of SWNTs

  15. Anti-HER2 IgY antibody-functionalized single-walled carbon nanotubes for detection and selective destruction of breast cancer cells

    International Nuclear Information System (INIS)

    Xiao, Yan; Savla, Ronak; Wagner, Paul D; Srivastava, Sudhir; He, Huixin; Gao, Xiugong; Taratula, Oleh; Treado, Stephen; Urbas, Aaron; Holbrook, R David; Cavicchi, Richard E; Avedisian, C Thomas; Mitra, Somenath

    2009-01-01

    Nanocarrier-based antibody targeting is a promising modality in therapeutic and diagnostic oncology. Single-walled carbon nanotubes (SWNTs) exhibit two unique optical properties that can be exploited for these applications, strong Raman signal for cancer cell detection and near-infrared (NIR) absorbance for selective photothermal ablation of tumors. In the present study, we constructed a HER2 IgY-SWNT complex and demonstrated its dual functionality for both detection and selective destruction of cancer cells in an in vitro model consisting of HER2-expressing SK-BR-3 cells and HER2-negative MCF-7 cells. The complex was constructed by covalently conjugating carboxylated SWNTs with anti-HER2 chicken IgY antibody, which is more specific and sensitive than mammalian IgGs. Raman signals were recorded on Raman spectrometers with a laser excitation at 785 nm. NIR irradiation was performed using a diode laser system, and cells with or without nanotube treatment were irradiated by 808 nm laser at 5 W/cm 2 for 2 min. Cell viability was examined by the calcein AM/ethidium homodimer-1 (EthD-1) staining. Using a Raman optical microscope, we found the Raman signal collected at single-cell level from the complex-treated SK-BR-3 cells was significantly greater than that from various control cells. NIR irradiation selectively destroyed the complex-targeted breast cancer cells without harming receptor-free cells. The cell death was effectuated without the need of internalization of SWNTs by the cancer cells, a finding that has not been reported previously. We have demonstrated that the HER2 IgY-SWNT complex specifically targeted HER2-expressing SK-BR-3 cells but not receptor-negative MCF-7 cells. The complex can be potentially used for both detection and selective photothermal ablation of receptor-positive breast cancer cells without the need of internalization by the cells. Thus, the unique intrinsic properties of SWNTs combined with high specificity and sensitivity of Ig

  16. Racial and Socioeconomic Disparities Are More Pronounced in Inflammatory Breast Cancer Than Other Breast Cancers

    Directory of Open Access Journals (Sweden)

    Ryan A. Denu

    2017-01-01

    Full Text Available Inflammatory breast cancer (IBC is a rare yet aggressive form of breast cancer. We examined differences in patient demographics and outcomes in IBC compared to locally advanced breast cancer (LABC and all other breast cancer patients from the Breast and Prostate Cancer Data Quality and Patterns of Care Study (POC-BP, containing information from cancer registries in seven states. Out of 7,624 cases of invasive carcinoma, IBC and LABC accounted for 2.2% (N=170 and 4.9% (N=375, respectively. IBC patients were more likely to have a higher number (P=0.03 and severity (P=0.01 of comorbidities than other breast cancer patients. Among IBC patients, a higher percentage of patients with metastatic disease versus nonmetastatic disease were black, on Medicaid, and from areas of higher poverty and more urban areas. Black and Hispanic IBC patients had worse overall and breast cancer-specific survival than white patients; moreover, IBC patients with Medicaid, patients from urban areas, and patients from areas of higher poverty and lower education had worse outcomes. These data highlight the effects of disparities in race and socioeconomic status on the incidence of IBC as well as IBC outcomes. Further work is needed to reveal the causes behind these disparities and methods to improve IBC outcomes.

  17. Chemical Constituents from Cimicifuga dahurica and Their Anti-Proliferative Effects on MCF-7 Breast Cancer Cells.

    Science.gov (United States)

    Huyen, Chu Thi Thanh; Luyen, Bui Thi Thuy; Khan, Ghulam Jilany; Oanh, Ha Van; Hung, Ta Manh; Li, Hui-Jun; Li, Ping

    2018-05-04

    This study was designed to search for novel anti-cancer compounds from natural plants. The 70% ethanolic extract from the rizhomes of Cimicifuga dahurica (Turcz.) Maxim. (Ranunculaceae) was found to possess significant in vitro anti-proliferative effects on MCF-7 breast cancer cells. A phytochemical investigation using assay-guided fractionation of the ethanolic extract of C. dahurica resulted in the isolation of one new phenolic amide glycoside 3 , two new lignan glycosides 4 and 7 , one new 9,19-cycloartane triterpenoid glycoside 6 , and thirteen known constituents 1 , 2 , 5 , and 8 ⁻ 17 . The structures of 3 , 4 , 6 , and 7 were established using contemporary NMR methods and from their HRESIMS data. The anti-proliferative effects of isolated compounds were evaluated using the BrdU-proliferation kit. Five among the 17 isolated compounds showed significant anti-proliferative effects ( p ≤ 0.05), wherein compound 7 showed the most significant anti-proliferative and cell cycle arresting effect ( p ≤ 0.05) which followed a dose dependent manner. Western blot protein expression analysis showed a down expression of c-Myc and cyclin D1 which further elucidated the anti-proliferation mechanism of compound 7 while apoptotic effects were found in association with Bcl-2 family protein expression variations. Conclusively this study reports the isolation and identification of 17 compounds from C. dahurica , including four novel molecules, in addition to the fact that compound 7 possesses significant anti-proliferative and apoptotic effects in vitro that may require further exploration.

  18. Cathepsin K induces platelet dysfunction and affects cell signaling in breast cancer - molecularly distinct behavior of cathepsin K in breast cancer

    International Nuclear Information System (INIS)

    Andrade, Sheila Siqueira; Gouvea, Iuri Estrada; Silva, Mariana Cristina C.; Castro, Eloísa Dognani; Paula, Cláudia A. A. de; Okamoto, Debora; Oliveira, Lilian; Peres, Giovani Bravin; Ottaiano, Tatiana; Facina, Gil; Nazário, Afonso Celso Pinto; Campos, Antonio Hugo J. F. M.; Paredes-Gamero, Edgar Julian; Juliano, Maria; Silva, Ismael D. C. G. da; Oliva, Maria Luiza V.; Girão, Manoel J. B. C.

    2016-01-01

    Breast cancer comprises clinically and molecularly distinct tumor subgroups that differ in cell histology and biology and show divergent clinical phenotypes that impede phase III trials, such as those utilizing cathepsin K inhibitors. Here we correlate the epithelial-mesenchymal-like transition breast cancer cells and cathepsin K secretion with activation and aggregation of platelets. Cathepsin K is up-regulated in cancer cells that proteolyze extracellular matrix and contributes to invasiveness. Although proteolytically activated receptors (PARs) are activated by proteases, the direct interaction of cysteine cathepsins with PARs is poorly understood. In human platelets, PAR-1 and −4 are highly expressed, but PAR-3 shows low expression and unclear functions. Platelet aggregation was monitored by measuring changes in turbidity. Platelets were immunoblotted with anti-phospho and total p38, Src-Tyr-416, FAK-Tyr-397, and TGFβ monoclonal antibody. Activation was measured in a flow cytometer and calcium mobilization in a confocal microscope. Mammary epithelial cells were prepared from the primary breast cancer samples of 15 women with Luminal-B subtype to produce primary cells. We demonstrate that platelets are aggregated by cathepsin K in a dose-dependent manner, but not by other cysteine cathepsins. PARs-3 and −4 were confirmed as the cathepsin K target by immunodetection and specific antagonists using a fibroblast cell line derived from PARs deficient mice. Moreover, through co-culture experiments, we show that platelets activated by cathepsin K mediated the up-regulation of SHH, PTHrP, OPN, and TGFβ in epithelial-mesenchymal-like cells from patients with Luminal B breast cancer. Cathepsin K induces platelet dysfunction and affects signaling in breast cancer cells. The online version of this article (doi:10.1186/s12885-016-2203-7) contains supplementary material, which is available to authorized users

  19. The Role of Exosomes in Breast Cancer.

    Science.gov (United States)

    Lowry, Michelle C; Gallagher, William M; O'Driscoll, Lorraine

    2015-12-01

    Although it has been long realized that eukaryotic cells release complex vesicular structures into their environment, only in recent years has it been established that these entities are not merely junk or debris, but that they are tailor-made specialized minimaps of their cell of origin and of both physiological and pathological relevance. These exosomes and microvesicles (ectosomes), collectively termed extracellular vesicles (EVs), are often defined and subgrouped first and foremost according to size and proposed origin (exosomes approximately 30-120 nm, endosomal origin; microvesicles 120-1000 nm, from the cell membrane). There is growing interest in elucidating the relevance and roles of EVs in cancer. Much of the pioneering work on EVs in cancer has focused on breast cancer, possibly because breast cancer is a leading cause of cancer-related deaths worldwide. This review provides an in-depth summary of such studies, supporting key roles for exosomes and other EVs in breast cancer cell invasion and metastasis, stem cell stimulation, apoptosis, immune system modulation, and anti-cancer drug resistance. Exosomes as diagnostic, prognostic, and/or predictive biomarkers and their potential use in the development of therapeutics are discussed. Although not fully elucidated, the involvement of exosomes in breast cancer development, progression, and resistance is becoming increasingly apparent from preclinical and clinical studies, with mounting interest in the potential exploitation of these vesicles for breast cancer biomarkers, as drug delivery systems, and in the development of future novel breast cancer therapies. © 2015 American Association for Clinical Chemistry.

  20. Mucin 1-specific immunotherapy in a mouse model of spontaneous breast cancer.

    Science.gov (United States)

    Mukherjee, Pinku; Madsen, Cathy S; Ginardi, Amelia R; Tinder, Teresa L; Jacobs, Fred; Parker, Joanne; Agrawal, Babita; Longenecker, B Michael; Gendler, Sandra J

    2003-01-01

    Human mucin 1 (MUC1) is an epithelial mucin glycoprotein that is overexpressed in 90% of all adenocarcinomas including breast, lung, pancreas, prostate, stomach, colon, and ovary. MUC1 is a target for immune intervention, because, in patients with solid adenocarcinomas, low-level cellular and humoral immune responses to MUC1 have been observed, which are not sufficiently strong to eradicate the growing tumor. The hypothesis for this study is that enhancing MUC1-specific immunity will result in antitumor immunity. To test this, the authors have developed a clinically relevant breast cancer model that demonstrates peripheral and central tolerance to MUC1 and develops spontaneous tumors of the mammary gland. In these mice, the authors tested a vaccine formulation comprised of liposomal-MUC1 lipopeptide and human recombinant interleukin-2. Results indicate that when compared with untreated mice, immunized mice develop T cells that express intracellular IFN-gamma, are reactive with MHC class I H-2Db/MUC1 tetramer, and are cytotoxic against MUC1-expressing tumor cells in vitro. The presence of MUC1-specific CTL did not translate into a clinical response as measured by time of tumor onset, tumor burden, and survival. The authors demonstrate that some of the immune-evasion mechanisms used by the tumor cells include downregulation of MHC-class I molecule, expression of TGF-beta2, and decrease in IFN-gamma -expressing effector T cells as tumors progress. Finally, utilizing an injectable breast cancer model, the authors show that targeting a single tumor antigen may not be an effective antitumor treatment, but that immunization with dendritic cells fed with whole tumor lysate is effective in breaking tolerance and protecting mice from subsequent tumor challenge. A physiologically relevant spontaneous breast cancer model has been developed to test improved immunotherapeutic approaches.

  1. A case of recurrence-mimicking charcoal granuloma in a breast cancer patient: Ultrasound,CT, PET/CT and breast-specific gamma imaging findings

    Energy Technology Data Exchange (ETDEWEB)

    Park, Dae Woong; Park, Ji Yeon; Park, Noh Hyuck; Kim, Seon Jeong; Shin, Hyuck Jai; Lee, Jeong Ju [Myongji Hospital, Seonam University College of Medicine, Goyang (Korea, Republic of); Yi, Seong Yoon [Div. of Hematology-Oncology, Dept. of Internal Medicine, Inje University Ilsan Paik Hospital, Goyang (Korea, Republic of)

    2016-07-15

    Charcoal remains stable without causing a foreign body reaction and it may be used for preoperative localization of a non-palpable breast mass. However, cases of post-charcoal-marking granuloma have only rarely been reported in the breast, and a charcoal granuloma can be misdiagnosed as malignancy. Herein, we report the ultrasound, computed tomography (CT), 18F-fluorodeoxyglucose-positron emission tomography/CT, and breast-specific gamma imaging findings of recurrence-mimicking charcoal granuloma after breast conserving surgery, following localization with charcoal in a breast cancer patient.

  2. Breast Cancer Overview

    Science.gov (United States)

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

  3. Breast Cancer -- Male

    Science.gov (United States)

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

  4. Lack of evidence for KRAS oncogenic mutations in triple-negative breast cancer

    International Nuclear Information System (INIS)

    Sánchez-Muñoz, Alfonso; Gallego, Elena; Luque, Vanessa de; Pérez-Rivas, Luís G; Vicioso, Luís; Ribelles, Nuria; Lozano, José; Alba, Emilio

    2010-01-01

    Mutational analysis of the KRAS gene has recently been established as a complementary in vitro diagnostic tool for the identification of patients with colorectal cancer who will not benefit from anti-epidermal growth factor receptor (EGFR) therapies. Assessment of the mutation status of KRAS might also be of potential relevance in other EGFR-overexpressing tumors, such as those occurring in breast cancer. Although KRAS is mutated in only a minor fraction of breast tumors (5%), about 60% of the basal-like subtype express EGFR and, therefore could be targeted by EGFR inhibitors. We aimed to study the mutation frequency of KRAS in that subtype of breast tumors to provide a molecular basis for the evaluation of anti-EGFR therapies. Total, genomic DNA was obtained from a group of 35 formalin-fixed paraffin-embedded, triple-negative breast tumor samples. Among these, 77.1% (27/35) were defined as basal-like by immunostaining specific for the established surrogate markers cytokeratin (CK) 5/6 and/or EGFR. KRAS mutational status was determined in the purified DNA samples by Real Time (RT)-PCR using primers specific for the detection of wild-type KRAS or the following seven oncogenic somatic mutations: Gly12Ala, Gly12Asp, Gly12Arg, Gly12Cys, Gly12Ser, Gly12Val and Gly13Asp. We found no evidence of KRAS oncogenic mutations in all analyzed tumors. This study indicates that KRAS mutations are very infrequent in triple-negative breast tumors and that EGFR inhibitors may be of potential benefit in the treatment of basal-like breast tumors, which overexpress EGFR in about 60% of all cases

  5. Study of phytochemical, anti-microbial, anti-oxidant, and anti-cancer properties of Allium wallichii.

    Science.gov (United States)

    Bhandari, Jaya; Muhammad, BushraTaj; Thapa, Pratiksha; Shrestha, Bhupal Govinda

    2017-02-08

    There is growing interest in the use of plants for the treatment and prevention of cancer. Medicinal plants are currently being evaluated as source of promising anticancer agents. In this paper, we have investigated the anticancer potential of plant Allium wallichii, a plant native to Nepal and growing at elevations of 2300-4800 m. This is the first study of its kind for the plant mentioned. The dried plant was extracted in aqueous ethanol. Phytochemical screening, anti-microbial assay, anti-oxidant assay, cytotoxicity assay and the flow-cytometric analysis were done for analyzing different phytochemicals present, anti-microbial activity, anti-oxidant activity and anti-cancer properties of Allium wallichii. We observed the presence of steroids, terpenoids, flavonoids, reducing sugars and glycosides in the plant extract and the plant showed moderate anti-microbial and anti-oxidant activity. The IC 50 values of Allium wallichii in different cancer cell lines are 69.69 μg/ml for Prostate cancer (PC3) cell line, 55.29 μg/ml for Breast Cancer (MCF-7) cell line and 46.51 μg/ml for cervical cancer (HeLa) cell line as compared to Doxorubicin (0.85 μg/ml). The cell viability assay using FACS showed that the IC 50 value of Allium wallichii for Burkitt's lymphoma (B-Lymphoma) cell line was 3.817 ± 1.99 mg/ml. Allium wallichii can be an important candidate to be used as an anticancer agent. Separation of pure compounds with bioassay guided extraction, spectrometric analysis and subsequent cytotoxicity assay of the pure bioactive compounds from Allium wallichii is highly recommended as the crude extract itself showed promising cytotoxicity.

  6. Archives of Breast Cancer: An Academic Multidisciplinary Breast Cancer Forum

    Directory of Open Access Journals (Sweden)

    Ahmad Kaviani

    2014-05-01

    development of a journal that will specifically publish breast-cancer-related articles and papers. It will pave the way for those who are interested in the subject and who seek to find the results of the most recent research in this field.Thus, this journal, as its main goal, provides an opportunity for better communication and interaction among medical practitioners, basic science researchers, and health care professionals interested in breast diseases. To achieve this goal, ABC benefits from one of the most qualified editorial boards selected from related specialties with various academic affiliations. The vision of ABC is to become a source of reliable and wellresearched articles focusing on breast cancer. Second, it intends to be an outstanding media, introducing to the world of medicine, cutting edge technologies, recent clinical approaches, diagnostic and practical methods, and even surgical details crucial in dealing with breast cancer. We hope that we can make a considerable contribution to the prevention, early detection, management, and rehabilitation of patients suffering from breast cancer. All the members of ABC editorial staff believe that collaboration and interaction amongthe related scientists, physicians and surgeons, social experts, and policy makers from the four corners of the world would be the ultimate means to achieve the goals of the journal.

  7. Plant Sterols as Anticancer Nutrients: Evidence for Their Role in Breast Cancer

    Directory of Open Access Journals (Sweden)

    Bruce J. Grattan

    2013-01-01

    Full Text Available While many factors are involved in the etiology of cancer, it has been clearly established that diet significantly impacts one’s risk for this disease. More recently, specific food components have been identified which are uniquely beneficial in mitigating the risk of specific cancer subtypes. Plant sterols are well known for their effects on blood cholesterol levels, however research into their potential role in mitigating cancer risk remains in its infancy. As outlined in this review, the cholesterol modulating actions of plant sterols may overlap with their anti-cancer actions. Breast cancer is the most common malignancy affecting women and there remains a need for effective adjuvant therapies for this disease, for which plant sterols may play a distinctive role.

  8. Establishment of H2Mab-119, an Anti-Human Epidermal Growth Factor Receptor 2 Monoclonal Antibody, Against Pancreatic Cancer.

    Science.gov (United States)

    Yamada, Shinji; Itai, Shunsuke; Nakamura, Takuro; Chang, Yao-Wen; Harada, Hiroyuki; Suzuki, Hiroyoshi; Kaneko, Mika K; Kato, Yukinari

    2017-12-01

    Human epidermal growth factor receptor 2 (HER2) is overexpressed in breast cancer and is associated with poor clinical outcomes. In addition, HER2 expression has been reported in other cancers, such as gastric, colorectal, lung, and pancreatic cancers. An anti-HER2 humanized antibody, trastuzumab, leads to significant survival benefits in patients with HER2-overexpressing breast cancers and gastric cancers. Herein, we established a novel anti-HER2 monoclonal antibody (mAb), H 2 Mab-119 (IgG 1 , kappa), and characterized its efficacy against pancreatic cancers using flow cytometry, Western blot, and immunohistochemical analyses. H 2 Mab-119 reacted with pancreatic cancer cell lines, such as KLM-1, Capan-2, and MIA PaCa-2, but did not react with PANC-1 in flow cytometry analysis. Western blot analysis also revealed a moderate signal for KLM-1 and a weak signal for MIA PaCa-2, although H 2 Mab-119 reacted strongly with LN229/HER2 cells. Finally, immunohistochemical analyses with H 2 Mab-119 revealed sensitive and specific reactions against breast and colon cancers but did not react with pancreatic cancers, indicating that H 2 Mab-119 is useful for detecting HER2 overexpression in pancreatic cancers using flow cytometry and Western blot analyses.

  9. Systematic drug screening reveals specific vulnerabilities and co-resistance patterns in endocrine-resistant breast cancer.

    Science.gov (United States)

    Kangaspeska, Sara; Hultsch, Susanne; Jaiswal, Alok; Edgren, Henrik; Mpindi, John-Patrick; Eldfors, Samuli; Brück, Oscar; Aittokallio, Tero; Kallioniemi, Olli

    2016-07-04

    The estrogen receptor (ER) inhibitor tamoxifen reduces breast cancer mortality by 31 % and has served as the standard treatment for ER-positive breast cancers for decades. However, 50 % of advanced ER-positive cancers display de novo resistance to tamoxifen, and acquired resistance evolves in 40 % of patients who initially respond. Mechanisms underlying resistance development remain poorly understood and new therapeutic opportunities are urgently needed. Here, we report the generation and characterization of seven tamoxifen-resistant breast cancer cell lines from four parental strains. Using high throughput drug sensitivity and resistance testing (DSRT) with 279 approved and investigational oncology drugs, exome-sequencing and network analysis, we for the first time, systematically determine the drug response profiles specific to tamoxifen resistance. We discovered emerging vulnerabilities towards specific drugs, such as ERK1/2-, proteasome- and BCL-family inhibitors as the cells became tamoxifen-resistant. Co-resistance to other drugs such as the survivin inhibitor YM155 and the chemotherapeutic agent paclitaxel also occurred. This study indicates that multiple molecular mechanisms dictate endocrine resistance, resulting in unexpected vulnerabilities to initially ineffective drugs, as well as in emerging co-resistances. Thus, combatting drug-resistant tumors will require patient-tailored strategies in order to identify new drug vulnerabilities, and to understand the associated co-resistance patterns.

  10. Breast cancer patterns and lifetime risk of developing breast cancer among Puerto Rican females.

    Science.gov (United States)

    Nazario, C M; Figueroa-Vallés, N; Rosario, R V

    2000-03-01

    The purpose of this study was to evaluate the epidemiologic patterns of breast cancer and to estimate the lifetime risk probability of developing breast cancer among Hispanic females using cancer data from Puerto Rico. The age-adjusted breast cancer incidence rate (per 100,000) in Puerto Rico increased from 15.3 in 1960-1964 to 43.3 in 1985-1989. The age-adjusted breast cancer mortality rate (per 100,000) increased from 5.7 to 10.6 comparing the same two time periods (1960-1964 vs 1985-1989). Nevertheless, in 1985-1989 breast cancer incidence rate was higher in US White females (110.8 per 100,000) compared to Puerto Rican females (51.4 per 100,000; age-adjusted to the 1970 US standard population). The breast cancer mortality rate was also higher in US White females (27.4 per 100,000) than in Puerto Rican females (15.1 per 100,000; age-adjusted to the 1970 US standard population) during 1985-1989. A multiple decrement life table was constructed applying age-specific incidence and mortality rates from cross-sectional data sets (1980-1984 and 1985-1989 data for Puerto Rican females and 1987-1989 SEER data sets for US White and Black females) to a hypothetical cohort of 10,000,000 women. The probability of developing invasive breast cancer was computed for the three groups using the long version of DEVCAN: Probability of DEVeloping CANcer software, version 3.3. The lifetime risk of developing breast cancer was 5.4% for Puerto Rican females, compared to 8.8% for US Black females and 13.0% for US White females. Lifetime risk for Puerto Rican females increased from 4.5% in 1980-1984 to 5.4% in 1985-1989. Lifetime risk of breast cancer appears to be increasing in Puerto Rico, but remains lower than the probability for US White females. Therefore, the application of lifetime probability of developing invasive breast cancer estimated for the US female population will overestimate the risk for the Puerto Rican female population.

  11. Surveillance mammography for detecting ipsilateral breast tumour recurrence and metachronous contralateral breast cancer: a systematic review

    Energy Technology Data Exchange (ETDEWEB)

    Robertson, Clare; Boachie, Charles; Fraser, Cynthia; MacLennan, Graeme; Mowatt, Graham; Thomas, Ruth E. [University of Aberdeen, Health Services Research Unit, Aberdeen (United Kingdom); Ragupathy, Senthil Kumar Arcot [NHS Grampian, Radiology Department, Aberdeen Royal Infirmary, Aberdeen (United Kingdom); Heys, Steve D. [University of Aberdeen and Aberdeen Royal Infirmary, NHS Grampian, Division of Applied Medicine, School of Medicine and Dentistry, Aberdeen (United Kingdom); Gilbert, Fiona J. [University of Aberdeen and Aberdeen Royal Infirmary, NHS Grampian, Aberdeen Biomedical Imaging Centre, Aberdeen (United Kingdom)

    2011-12-15

    To determine the diagnostic accuracy of surveillance mammography for detecting ipsilateral breast tumour recurrence and metachronous contralateral breast cancer in women previously treated for primary breast cancer. A systematic review of surveillance mammography compared with ultrasound, magnetic resonance imaging (MRI), specialist-led clinical examination or unstructured primary care follow-up, using histopathological assessment for test positives and follow-up for test negatives as the reference standard. Nine studies met our inclusion criteria. Variations in study comparisons precluded meta-analysis. For routine ipsilateral breast tumour detection, surveillance mammography sensitivity ranged from 64-67% and specificity ranged from 85-97%. For MRI, sensitivity ranged from 86-100% and specificity was 93%. For non-routine ipsilateral breast tumour detection, sensitivity and specificity for surveillance mammography ranged from 50-83% and 57-75% and for MRI 93-100% and 88-96%. For routine metachronous contralateral breast cancer detection, one study reported sensitivity of 67% and specificity of 50% for both surveillance mammography and MRI. Although mammography is associated with high sensitivity and specificity, MRI is the most accurate test for detecting ipsilateral breast tumour recurrence and metachronous contralateral breast cancer in women previously treated for primary breast cancer. Results should be interpreted with caution because of the limited evidence base. (orig.)

  12. Breast cancer with axillary lymph node involvement

    International Nuclear Information System (INIS)

    Belaid, A.; Kanoun, S.; Kallel, A.; Ghorbel, I.; Azoury, F.; Heymann, S.; Marsiglia, H.; Bourgier, C.; Belaid, A.; Ghorbel, I.; Kanoun, S.; Kallel, A.; Pichenot, C.; Verstraet, R.; Marsiglia, H.

    2010-01-01

    Breast cancer is the most frequent cancer of women in western countries. There are one million new cases per year in the world which represents 22% of all female cancers, and more than 370.000 deaths due to breast cancer per year (14% of cancer mortality). More than half of breast cancers are associated with axillary nodal involvement. Post-operative radiation therapy (XRT) is a crucial part of locoregional treatment in axillary nodal involvement breast cancer owing to a 15-years risk reduction of locoregional recurrence of 70% and to a 5.4% risk reduction of specific mortality. In 3D-conformal irradiation in such breast cancers, target volumes are chest wall when mastectomy was performed or breast and boost of tumor bed in case of breast conservative surgery, and supra-clavicular and/or axillary and/or internal mammary node areas. The main organs at risk are ipsilateral lung, heart and brachial plexus. The aim of this article is to describe epidemiologic, radio anatomic and prognostic features of axillary nodal involvement breast cancer and to propose guidelines for 3D-conformal treatment planning in locally advanced breast cancers. This review is illustrated by a case report. (authors)

  13. Breast Cancer Surgery

    Science.gov (United States)

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

  14. A Physical Mechanism and Global Quantification of Breast Cancer.

    Directory of Open Access Journals (Sweden)

    Chong Yu

    Full Text Available Initiation and progression of cancer depend on many factors. Those on the genetic level are often considered crucial. To gain insight into the physical mechanisms of breast cancer, we construct a gene regulatory network (GRN which reflects both genetic and environmental aspects of breast cancer. The construction of the GRN is based on available experimental data. Three basins of attraction, representing the normal, premalignant and cancer states respectively, were found on the phenotypic landscape. The progression of breast cancer can be seen as switching transitions between different state basins. We quantified the stabilities and kinetic paths of the three state basins to uncover the biological process of breast cancer formation. The gene expression levels at each state were obtained, which can be tested directly in experiments. Furthermore, by performing global sensitivity analysis on the landscape topography, six key genes (HER2, MDM2, TP53, BRCA1, ATM, CDK2 and four regulations (HER2⊣TP53, CDK2⊣BRCA1, ATM→MDM2, TP53→ATM were identified as being critical for breast cancer. Interestingly, HER2 and MDM2 are the most popular targets for treating breast cancer. BRCA1 and TP53 are the most important oncogene of breast cancer and tumor suppressor gene, respectively. This further validates the feasibility of our model and the reliability of our prediction results. The regulation ATM→MDM2 has been extensive studied on DNA damage but not on breast cancer. We notice the importance of ATM→MDM2 on breast cancer. Previous studies of breast cancer have often focused on individual genes and the anti-cancer drugs are mainly used to target the individual genes. Our results show that the network-based strategy is more effective on treating breast cancer. The landscape approach serves as a new strategy for analyzing breast cancer on both the genetic and epigenetic levels and can help on designing network based medicine for breast cancer.

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

    Science.gov (United States)

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

    2010-01-01

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

  16. Mutation analysis of breast cancer gene BRCA among breast cancer Jordanian females

    International Nuclear Information System (INIS)

    Atoum, Manar F.; Al-Kayed, Sameer A.

    2004-01-01

    To screen mutations of the tumor suppressor breast cancer susceptibility gene 1 (BRCA1) within 3 exons among Jordanian breast cancer females. A total of 135 Jordanian breast cancer females were genetically analyzed by denaturing gradient electrophoresis (DGGE) for mutation detection in 3 BRCA1 exons (2, 11 and 20) between 2000-2002 in Al-Basheer Hospital, Amman, Jordan. Of the studied patients 50 had a family history of breast cancer, 28 had a family history of cancer other than breast cancer, and 57 had no family history of any cancer. Five germline mutations were detected among breast cancer females with a family history of breast cancers (one in exon 2 and 4 mutations in exon 11). Another germline mutation (within exon 11) was detected among breast cancer females with family history of cancer other than breast cancer, and no mutation was detected among breast cancer females with no family history of any cancer or among normal control females. Screening mutations within exon 2, exon 11 and exon 20 showed that most screened mutations were within BRCA1 exon 11 among breast cancer Jordanian families with a family history of breast cancer. (author)

  17. Epigenetics in Breast and Prostate Cancer

    OpenAIRE

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

    2015-01-01

    Most recent investigations into cancer etiology have identified a key role played by epigenetics. Specifically, aberrant DNA and histone modifications which silence tumor suppressor genes or promote oncogenes have been demonstrated in multiple cancer models. While the role of epigenetics in several solid tumor cancers such as colorectal cancer are well established, there is emerging evidence that epigenetics also plays a critical role in breast and prostate cancer. In breast cancer, DNA methy...

  18. 6 Common Cancers - Breast Cancer

    Science.gov (United States)

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

  19. Worse survival after breast cancer in women with anorexia nervosa.

    Science.gov (United States)

    Bens, Annet; Papadopoulos, Fotios C; Pukkala, Eero; Ekbom, Anders; Gissler, Mika; Mellemkjær, Lene

    2018-04-01

    A history of anorexia nervosa has been associated with a reduced risk of developing breast cancer. We investigated survival after breast cancer among women with a prior anorexia nervosa diagnosis compared with women in a population comparison group. This register-based study included combined data from Sweden, Denmark and Finland. A total of 76 and 1462 breast cancer cases identified among 22,654 women with anorexia nervosa and 224,619 women in a population comparison group, respectively, were included in the study. Hazard ratios (HR) for overall and breast cancer-specific mortality after breast cancer diagnosis were estimated using Cox regression. Cause of death was available only for Swedish and Danish women; therefore, the analysis on breast cancer-specific mortality was restricted to these women. We observed 23 deaths after breast cancer among anorexia nervosa patients and 247 among population comparisons. The overall mortality after the breast cancer diagnosis was increased in women with a history of anorexia nervosa compared with population comparisons (HR 2.5, 95% CI 1.6-3.9) after adjustment for age, period and extent of disease. Results were similar for overall (HR 2.3, 95% CI 1.4-3.6) and breast cancer-specific mortality (HR 2.1, 95% CI 1.3-3.6) among Swedish and Danish women. We found that female breast cancer patients with a prior diagnosis of anorexia nervosa have a worse survival compared with other breast cancer patients.

  20. Circulating microRNAs in breast cancer

    DEFF Research Database (Denmark)

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

    2017-01-01

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

  1. INHIBITION OF SPONTANEOUS APOPTOSIS IN HUMAN BREAST CANCER

    Institute of Scientific and Technical Information of China (English)

    邵志敏; 江明; 吴炅; 余黎民; 韩企夏; 张延璆; 沈镇宙

    1996-01-01

    Breast tumorigenesis proceeds through an accumulation of specific genetic alteration. Breast malignant transformation is dependent on not only the rate of cell production but also on apoptcsis,a genetically prograined process of autonomous ceil death. We investigated whether breast tumorigenesis involved an altered susceptibility to apoptosis and proliferation by examining normal breast epithelium and breast cancer sampies. We found there is a great inhibition of spontaneous apoptosis in breast cancer ceils compared with normal breast epithelium. The inhibition of apoptosis in breast cancer may contribute to neoplastic transformation.

  2. Danish Breast Cancer Cooperative Group

    DEFF Research Database (Denmark)

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

    2016-01-01

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

  3. Conventional surgery in breast cancer

    International Nuclear Information System (INIS)

    Tapia Herrera, Andres

    2013-01-01

    General aspects of breast cancer were described from the epidemiological point of view, clinical and pathological, as well as its impact at global and national levels. Parenchyma conservative surgery and/or breast skin was analyzed exhaustively as a cancer treatment analyzed exhaustively, to your specifications, requirements, technical aspects, risks, benefits, degree of oncological safety and benefits for patients [es

  4. Breast Cancer After Chest Radiation Therapy for Childhood Cancer

    Science.gov (United States)

    Moskowitz, Chaya S.; Chou, Joanne F.; Wolden, Suzanne L.; Bernstein, Jonine L.; Malhotra, Jyoti; Friedman, Danielle Novetsky; Mubdi, Nidha Z.; Leisenring, Wendy M.; Stovall, Marilyn; Hammond, Sue; Smith, Susan A.; Henderson, Tara O.; Boice, John D.; Hudson, Melissa M.; Diller, Lisa R.; Bhatia, Smita; Kenney, Lisa B.; Neglia, Joseph P.; Begg, Colin B.; Robison, Leslie L.; Oeffinger, Kevin C.

    2014-01-01

    Purpose The risk of breast cancer is high in women treated for a childhood cancer with chest irradiation. We sought to examine variations in risk resulting from irradiation field and radiation dose. Patients and Methods We evaluated cumulative breast cancer risk in 1,230 female childhood cancer survivors treated with chest irradiation who were participants in the CCSS (Childhood Cancer Survivor Study). Results Childhood cancer survivors treated with lower delivered doses of radiation (median, 14 Gy; range, 2 to 20 Gy) to a large volume (whole-lung field) had a high risk of breast cancer (standardized incidence ratio [SIR], 43.6; 95% CI, 27.2 to 70.3), as did survivors treated with high doses of delivered radiation (median, 40 Gy) to the mantle field (SIR, 24.2; 95% CI, 20.7 to 28.3). The cumulative incidence of breast cancer by age 50 years was 30% (95% CI, 25 to 34), with a 35% incidence among Hodgkin lymphoma survivors (95% CI, 29 to 40). Breast cancer–specific mortality at 5 and 10 years was 12% (95% CI, 8 to 18) and 19% (95% CI, 13 to 25), respectively. Conclusion Among women treated for childhood cancer with chest radiation therapy, those treated with whole-lung irradiation have a greater risk of breast cancer than previously recognized, demonstrating the importance of radiation volume. Importantly, mortality associated with breast cancer after childhood cancer is substantial. PMID:24752044

  5. Metronomic Cyclophosphamide and Methotrexate Chemotherapy Combined with 1E10 Anti-Idiotype Vaccine in Metastatic Breast Cancer

    International Nuclear Information System (INIS)

    Soriano, J.L.; Batista, N.; Lima, M.; Gonzalez, J.; Garcia, R.; Zarza, Y.; Lopez, M.V.; Rodriguez, M.; Loys, J.L.; Montejo, N.; Santiesteban, E.; Aguirre, F.; Macias, A.; Vazquez, A.M.

    2011-01-01

    The use of low doses of cytotoxic agents continuously for prolonged periods is an alternative for the treatment of patients with metastatic breast cancer who have developed resistance to conventional chemotherapy. The combination of metronomic chemotherapy with therapeutic vaccines might increase the efficacy of the treatment. Twenty one patients with metastatic breast cancer in progression and a Karnosky index =60%, were treated with metronomic chemotherapy (50?mg of cyclophosphamide orally daily and 2.5 mg of methotrexate orally bi-daily), in combination with five bi-weekly subcutaneous injections of 1 mg of aluminum hydroxide-precipitated 1E10 anti-idiotype MAb (1E10-Alum), followed by re immunizations every 28 days. Five patients achieved objective response, eight showed stable disease and eight had disease progression. Median time to progression was 9,8 months, while median overall survival time was 12,93 months. The median duration of the response (CR+PR+SD) was 18,43 months (12,20-24,10 months), being higher than 12 months in 76,9% of the patients. Overall toxicity was generally mild. Metronomic chemotherapy combined with 1E10-Alum vaccine immunotherapy might be a useful therapeutic option for the treatment of metastatic breast cancer due to its potential impact on survival and patient quality of live, low toxicity and advantages of the administration.

  6. Chemical Constituents from Cimicifuga dahurica and Their Anti-Proliferative Effects on MCF-7 Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Chu Thi Thanh Huyen

    2018-05-01

    Full Text Available This study was designed to search for novel anti-cancer compounds from natural plants. The 70% ethanolic extract from the rizhomes of Cimicifuga dahurica (Turcz. Maxim. (Ranunculaceae was found to possess significant in vitro anti-proliferative effects on MCF-7 breast cancer cells. A phytochemical investigation using assay-guided fractionation of the ethanolic extract of C. dahurica resulted in the isolation of one new phenolic amide glycoside 3, two new lignan glycosides 4 and 7, one new 9,19-cycloartane triterpenoid glycoside 6, and thirteen known constituents 1, 2, 5, and 8–17. The structures of 3, 4, 6, and 7 were established using contemporary NMR methods and from their HRESIMS data. The anti-proliferative effects of isolated compounds were evaluated using the BrdU-proliferation kit. Five among the 17 isolated compounds showed significant anti-proliferative effects (p ≤ 0.05, wherein compound 7 showed the most significant anti-proliferative and cell cycle arresting effect (p ≤ 0.05 which followed a dose dependent manner. Western blot protein expression analysis showed a down expression of c-Myc and cyclin D1 which further elucidated the anti-proliferation mechanism of compound 7 while apoptotic effects were found in association with Bcl-2 family protein expression variations. Conclusively this study reports the isolation and identification of 17 compounds from C. dahurica, including four novel molecules, in addition to the fact that compound 7 possesses significant anti-proliferative and apoptotic effects in vitro that may require further exploration.

  7. Statin use and breast cancer risk in the Nurses’ Health Study

    Science.gov (United States)

    Borgquist, Signe; Tamimi, Rulla M.; Chen, Wendy Y.; Garber, Judy E.; Eliassen, A. Heather; Ahern, Thomas P.

    2016-01-01

    Pre-clinical studies support an anti-cancer effect of statin drugs, yet epidemiological evidence remains inconsistent regarding their role in breast cancer primary prevention. Here we report an updated analysis of the association between statin use and breast cancer incidence in the Nurses’ Health Study cohort. Post-menopausal Nurses’ Health Study participants without a cancer history were followed from 2000 until 2012 (n=79,518). Data on statin use were retrieved from biennial questionnaires. We fit Cox regression models to estimate associations between longitudinal statin use and breast cancer incidence. Over 823,086 person-years of follow-up, 3,055 cases of invasive breast cancer occurred. Compared with never users, both former and current statin users had similar rates of invasive breast cancer incidence (former users: HRadj=0.96, 95% CI: 0.82, 1.1; current users: HRadj=1.1, 95% CI: 0.92, 1.3). Associations did not differ by estrogen receptor status or histology (ductal vs. lobular carcinoma). Statin use was not associated with risk of invasive breast cancer, irrespective of histological subtype and ER status. Statin drugs do not appear to modify processes involved in breast cancer initiation. PMID:26762806

  8. Aromatase inhibitors and breast cancer prevention.

    Science.gov (United States)

    Litton, Jennifer Keating; Arun, Banu K; Brown, Powel H; Hortobagyi, Gabriel N

    2012-02-01

    Endocrine therapy with selective estrogen receptor modulators (SERMs) has been the mainstay of breast cancer prevention trials to date. The aromatase inhibitors, which inhibit the final chemical conversion of androgens to estrogens, have shown increased disease-free survival benefit over tamoxifen in patients with primary hormone receptor-positive breast cancer, as well as reducing the risk of developing contralateral breast cancers. The aromatase inhibitors are being actively evaluated as prevention agents for women with a history of ductal carcinoma in situ as well as for women who are considered to be at high risk for developing primary invasive breast cancer. This review evaluates the available prevention data, as evidenced by the decrease in contralateral breast cancers, when aromatase inhibitors are used in the adjuvant setting, as well as the emerging data of the aromatase inhibitors specifically tested in the prevention setting for women at high risk. Exemestane is a viable option for breast cancer prevention. We continue to await further follow-up on exemestane as well as other aromatase inhibitors in the prevention setting for women at high risk of developing breast cancer or with a history of ductal carcinoma in situ.

  9. Breast cancer

    International Nuclear Information System (INIS)

    Tokunaga, Masayoshi

    1992-01-01

    More than 20-year follow-up of A-bomb survivors in Hiroshima and Nagasaki has a crucial role in determining the relationship of radiation to the occurrence of breast cancer. In 1967, Wanebo et al have first reported 27 cases of breast cancer during the period 1950-1966 among the Adult Health Study population of A-bomb survivors. Since then, follow-up surveys for breast cancer have been made using the Life Span Study (LSS) cohort, and the incidence of breast cancer has increased year by year; that is breast cancer was identified in 231 cases by the first LSS series (1950-1969), 360 cases by the second LSS series (1950-1974), 564 cases by the third LSS series (1950-1980), and 816 cases in the fourth LSS series (1950-1085). The third LSS series have revealed a high risk for radiation-induced breast cancer in women aged 10 or less at the time of exposure (ATE). Both relative and absolute risks are found to be decreased with increasing ages ATE. Based on the above-mentioned findings and other studies on persons exposed medical radiation, radiation-induced breast cancer is characterized by the following: (1) the incidence of breast cancer is linearly increased with increasing radiation doses; (2) both relative and absolute risks for breast cancer are high in younger persons ATE; (3) age distribution of breast cancer in proximally exposed A-bomb survivors is the same as that in both distally A-bomb survivors and non-exposed persons, and there is no difference in histology between the former and latter groups. Thus, immature mammary gland cells before the age of puberty are found to be most radiosensitive. (N.K.)

  10. A biomimetic collagen derived peptide exhibits anti-angiogenic activity in triple negative breast cancer.

    Directory of Open Access Journals (Sweden)

    Elena V Rosca

    Full Text Available We investigated the application of a mimetic 20 amino acid peptide derived from type IV collagen for treatment of breast cancer. We showed that the peptide induced a decrease of proliferation, adhesion, and migration of endothelial and tumor cells in vitro. We also observed an inhibition of triple negative MDA-MB-231 xenograft growth by 75% relative to control when administered intraperitoneally for 27 days at 10 mg/kg. We monitored in vivo the changes in vascular properties throughout the treatment using MRI and found that the vascular volume and permeability surface area product decreased significantly. The treatment also resulted in an increase of caspase-3 activity and in a reduction of microvascular density. The multiple mode of action of this peptide, i.e., anti-angiogenic, and anti-tumorigenic, makes it a viable candidate as a therapeutic agent as a monotherapy or in combination with other compounds.

  11. Breast cancer chemopreventive and chemotherapeutic effects of Camellia Sinensis (green tea): an updated review.

    Science.gov (United States)

    Rafieian-Kopaei, Mahmoud; Movahedi, Mino

    2017-02-01

    Camellia sinensis belongs to the plant family of Theaceae, native to East Asia, the Indian Subcontinent and Southeast Asia, but naturalized in many parts of the world. The aim of this study was to overview its anti-breast cancer chemopreventive and chemotherapeutic effects. This review article is aimed to overview breast cancer chemopreventive and chemotherapeutic effects of Camellia sinensis (green tea). This review article was carried out by searching studies in PubMed, Medline, Web of Science, and IranMedex databases. The initial search strategy identified around 108 references. In this study, 68 studies were accepted for further screening, and met all our inclusion criteria [in English, full text, chemopreventive and chemotherapeutic effects of Camellia sinensis and dated mainly from the year 1999 to 2016. The search terms were Camellia sinensis, chemopreventive, chemotherapeutic properties, pharmacological effects. The result of this study suggested that the catechin available in Camellia sinensis has properties which can prevent and treat breast cancer. It has also been shown to inhibit proliferation of breast cancer cells and to block carcinogenesis. It was found that increased Camellia sinensis consumption may lower the risk of breast cancer. Camellia sinensis intake was shown to reduce the risk of breast cancer incidence. In addition, potential breast cancer chemopreventive effect of Camellia sinensis both in vivo and in vitro was highly confirmed. However, the evidence of low effect and no effect was observed. More clinical trial studies are needed to prove its anti-breast cancer activity decisively. Camellia sinensis is broadly utilized as a part of customary medication since antiquated time because of its cost adequacy, and fewer reaction properties. The studies demonstrated anti-breast cancer activity of Camellia sinensis and its component by adjusting cell signaling pathways such as angiogenesis, apoptosis, and transcription factor. Furthermore

  12. Bromodomain protein 4 discriminates tissue-specific super-enhancers containing disease-specific susceptibility loci in prostate and breast cancer

    DEFF Research Database (Denmark)

    Zuber, Verena; Bettella, Francesco; Witoelar, Aree

    2017-01-01

    progression. Although previous approaches have been tried to explain risk associated with SNPs in regulatory DNA elements, so far epigenetic readers such as bromodomain containing protein 4 (BRD4) and super-enhancers have not been used to annotate SNPs. In prostate cancer (PC), androgen receptor (AR) binding......Background: Epigenetic information can be used to identify clinically relevant genomic variants single nucleotide polymorphisms (SNPs) of functional importance in cancer development. Super-enhancers are cell-specific DNA elements, acting to determine tissue or cell identity and driving tumor...... the differential enrichment of SNPs mapping to specific categories of enhancers. We find that BRD4 is the key discriminant of tissue-specific enhancers, showing that it is more powerful than AR binding information to capture PC specific risk loci, and can be used with similar effect in breast cancer (BC...

  13. Breast Cancer

    Science.gov (United States)

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

  14. Method for in-vivo NMR measurements in the human breast to screen for small breast cancer in an otherwise healthy breast

    International Nuclear Information System (INIS)

    Rollwitz, W.L.

    1986-01-01

    A method is described of conducting a noninvasive female breast cancer test comprising the steps of: (a) forming an inhomogeneous magnetic field between the poles of a magnet wherein the magnetic field defines a specific volume between the poles wherein the specific volume has a specified magnetic field intensity H/sub o/ for NMR testing and the specific volume extends outwardly to an edge defined by the outer edge of the female breast; (b) moving incrementally the specific volume from a beginning point toward an ending point to scan a breast between the pole pieces of the magnet and thereby move the specific volume through the breast the movement being with N examinations located along the breast at different locations wherein each specific volume has the defined thickness and outward extent; (c) periodically interrogating by a transmitted pulse from a coil into the breast portion located in the specific volume for NMR response wherein the NMR response is dependent on hydrogen in the water, and the water has two states, one state in cancer cells and the other state in healthy tissue, and the cancer cells provide a different NMR response compared with water in the healthy tissue, the step of interrogating including first and second NMR interrogations of specific breast volumes forming NMR responses; (d) wherein the magnetic field intensity in the specific volume and the pulse from the coil cause an NMR response from water in the body tissue making up the breast portion; and (e) determining cancer cell anomalies arising from cancer cells in the breast as indicated by comparison of the NMR water responses to form difference signals

  15. Remodeling of the methylation landscape in breast cancer metastasis.

    Directory of Open Access Journals (Sweden)

    Marsha Reyngold

    Full Text Available The development of breast cancer metastasis is accompanied by dynamic transcriptome changes and dramatic alterations in nuclear and chromatin structure. The basis of these changes is incompletely understood. The DNA methylome of primary breast cancers contribute to transcriptomic heterogeneity and different metastatic behavior. Therefore we sought to characterize methylome remodeling during regional metastasis. We profiled the DNA methylome and transcriptome of 44 matched primary breast tumors and regional metastases. Striking subtype-specific patterns of metastasis-associated methylome remodeling were observed, which reflected the molecular heterogeneity of breast cancers. These divergent changes occurred primarily in CpG island (CGI-poor areas. Regions of methylome reorganization shared by the subtypes were also observed, and we were able to identify a metastasis-specific methylation signature that was present across the breast cancer subclasses. These alterations also occurred outside of CGIs and promoters, including sequences flanking CGIs and intergenic sequences. Integrated analysis of methylation and gene expression identified genes whose expression correlated with metastasis-specific methylation. Together, these findings significantly enhance our understanding of the epigenetic reorganization that occurs during regional breast cancer metastasis across the major breast cancer subtypes and reveal the nature of methylome remodeling during this process.

  16. Claudin-2 is an independent negative prognostic factor in breast cancer and specifically predicts early liver recurrences.

    Science.gov (United States)

    Kimbung, Siker; Kovács, Anikó; Bendahl, Pär-Ola; Malmström, Per; Fernö, Mårten; Hatschek, Thomas; Hedenfalk, Ingrid

    2014-02-01

    Predicting any future metastatic site of early-stage breast cancer is important as it significantly influences the prognosis of advanced disease. This study aimed at investigating the potential of claudin-2, over-expressed in breast cancer liver metastases, as a biomarker for predicting liver metastatic propensity in primary breast cancer. Claudin-2 expression was analyzed in two independent cohorts. Cohort 1 included 304 women with metastatic breast cancer diagnosed between 2002 and 2007, while cohort 2 included 237 premenopausal women with early-stage node-negative breast cancer diagnosed between 1991 and 1994. Global transcriptional profiling of fine-needle aspirates from metastases was performed, followed by immunohistochemical analyses in archival primary tumor tissue. Associations between claudin-2 expression and relapse site were assessed by univariable and multivariable Cox regression models including conventional prognostic factors. Two-sided statistical tests were used. CLDN2 was significantly up-regulated (P diagnosis and liver-specific recurrence was observed among patients with high levels of claudin-2 expression in the primary tumor (cohort 1, HR = 2.3, 95% CI = 1.3-3.9). These results suggest a novel role for claudin-2 as a prognostic biomarker with the ability to predict not only the likelihood of a breast cancer recurrence, but more interestingly, the liver metastatic potential of the primary tumor. Copyright © 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  17. Cause-specific mortality in long-term survivors of breast cancer: A 25-year follow-up study

    International Nuclear Information System (INIS)

    Hooning, Maartje J.; Aleman, Berthe M.P.; Rosmalen, Agnes J.M. van; Kuenen, Marianne A.; Klijn, Jan G.M.; Leeuwen, Flora E. van

    2006-01-01

    Purpose: To assess long-term cause-specific mortality in breast cancer patients. Patients and Methods: We studied mortality in 7425 patients treated for early breast cancer between 1970 and 1986. Follow-up was 94% complete until January 2000. Treatment-specific mortality was evaluated by calculating standardized mortality ratios (SMRs) based on comparison with general population rates and by using Cox proportional hazards regression. Results: After a median follow-up of 13.8 years, 4160 deaths were observed, of which 76% were due to breast cancer. Second malignancies showed a slightly increased SMR of 1.2 (95% confidence interval [CI], 1.0-1.3). Radiotherapy (RT) as compared with surgery was associated with a 1.7-fold (95% CI, 1.2-2.5) increased mortality from cardiovascular disease (CVD). After postlumpectomy RT, no increased mortality from CVD was observed (hazard ratio, 1.0; 95% CI, 0.5-1.9). Postmastectomy RT administered before 1979 and between 1979 and 1986 was associated with a 2-fold (95% CI, 1.2-3.4) and 1.5-fold (95% CI, 0.9-2.7) increase, respectively. Patients treated before age 45 experienced a higher SMR (2.0) for both solid tumors (95% CI, 1.6-2.7) and CVD (95% CI, 1.3-3.1). Conclusion: Currently, a large population of breast cancer survivors is at increased risk of death from CVDs and second cancers, especially when treated with RT at a young age. Patients irradiated after 1979 experience low (postmastectomy RT) or no (postlumpectomy RT) excess mortality from CVD

  18. DEGRO practical guidelines. Radiotherapy of breast cancer I. Radiotherapy following breast conserving therapy for invasive breast cancer

    International Nuclear Information System (INIS)

    Sedlmayer, F.

    2013-01-01

    irradiation strategies as well as WBI hypofractionation schedules. The potential of both in replacing normofractionated WBI has not yet been finally clarified. Conclusion: After breast conserving surgery, no subgroup even in low risk patients has yet been identified for whom radiotherapy can be safely omitted without compromising local control and, hence, cancer-specific survival. In most patients, this translates into an overall survival benefit. (orig.)

  19. Abbreviated MRI protocols for detecting breast cancer in women with dense breasts

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    Chen, Shung Qing; Huang, Min; Shen, Yu Ying; Liu, Chen Lu; Xu, Chuan Xiao [The Affiliated Suzhou Hospital, Nanjing Medical University, Suzhou (China)

    2017-06-15

    To evaluate the validity of two abbreviated protocols (AP) of MRI in breast cancer screening of dense breast tissue. This was a retrospective study in 356 participants with dense breast tissue and negative mammography results. The study was approved by the Nanjing Medical University Ethics Committee. Patients were imaged with a full diagnostic protocol (FDP) of MRI. Two APs (AP-1 consisting of the first post-contrast subtracted [FAST] and maximum-intensity projection [MIP] images, and AP-2 consisting of AP-1 combined with diffusion-weighted imaging [DWI]) and FDP images were analyzed separately, and the sensitivities and specificities of breast cancer detection were calculated. Of the 356 women, 67 lesions were detected in 67 women (18.8%) by standard MR protocol, and histological examination revealed 14 malignant lesions and 53 benign lesions. The average interpretation time of AP-1 and AP-2 were 37 seconds and 54 seconds, respectively, while the average interpretation time of the FDP was 3 minutes and 25 seconds. The sensitivities of the AP-1, AP-2, and FDP were 92.9, 100, and 100%, respectively, and the specificities of the three MR protocols were 86.5, 95.0, and 96.8%, respectively. There was no significant difference among the three MR protocols in the diagnosis of breast cancer (p > 0.05). However, the specificity of AP-1 was significantly lower than that of AP-2 (p = 0.031) and FDP (p = 0.035), while there was no difference between AP-2 and FDP (p > 0.05). The AP may be efficient in the breast cancer screening of dense breast tissue. FAST and MIP images combined with DWI of MRI are helpful to improve the specificity of breast cancer detection.

  20. Bioactivity of Turmeric-Derived Curcuminoids and Related Metabolites in Breast Cancer

    Science.gov (United States)

    Wright, Laura E.; Frye, Jen B.; Gorti, Bhavana; Timmermann, Barbara N.; Funk, Janet L.

    2013-01-01

    While the chemotherapeutic effect of curcumin, one of three major curcuminoids derived from turmeric, has been reported, largely unexplored are the effects of complex turmeric extracts more analogous to traditional medicinal preparations, as well as the relative importance of the three curcuminoids and their metabolites as anti-cancer agents. These studies document the pharmacodynamic effects of chemically-complex turmeric extracts relative to curcuminoids on human breast cancer cell growth and tumor cell secretion of parathyroid hormone-related protein (PTHrP), an important driver of cancer bone metastasis. Finally, relative effects of structurally-related metabolites of curcuminoids were assessed on the same endpoints. We report that 3 curcuminoid-containing turmeric extracts differing with respect to the inclusion of additional naturally occurring chemicals (essential oils and/or polar compounds) were equipotent in inhibiting human breast cancer MDA-MB-231 cell growth (IC50=10–16μg/mL) and secretion of osteolytic PTHrP (IC50=2–3μg/mL) when concentrations were normalized to curcuminoid content. Moreover, these effects were curcuminoid-specific, as botanically-related gingerol containing extracts had no effect. While curcumin and bis-demethoxycurcumin were equipotent to each other and to the naturally occurring curcuminoid mixture (IC50=58 μM), demethoxycurcumin was without effect on cell growth. However, each of the individual curcuminoids inhibited PTHrP secretion (IC50=22–31μM) to the same degree as the curcuminoid mixture (IC50=16 μM). Degradative curcuminoid metabolites (vanillin and ferulic acid) did not inhibit cell growth or PTHrP, while reduced metabolites (tetrahydrocurcuminoids) had inhibitory effects on cell growth and PTHrP secretion but only at concentrations ≥10-fold higher than the curcuminoids. These studies emphasize the structural and biological importance of curcuminoids in the anti-breast cancer effects of turmeric and contradict

  1. Molecular Features of Subtype-Specific Progression from Ductal Carcinoma In Situ to Invasive Breast Cancer

    Directory of Open Access Journals (Sweden)

    Robert Lesurf

    2016-07-01

    Full Text Available Breast cancer consists of at least five main molecular “intrinsic” subtypes that are reflected in both pre-invasive and invasive disease. Although previous studies have suggested that many of the molecular features of invasive breast cancer are established early, it is unclear what mechanisms drive progression and whether the mechanisms of progression are dependent or independent of subtype. We have generated mRNA, miRNA, and DNA copy-number profiles from a total of 59 in situ lesions and 85 invasive tumors in order to comprehensively identify those genes, signaling pathways, processes, and cell types that are involved in breast cancer progression. Our work provides evidence that there are molecular features associated with disease progression that are unique to the intrinsic subtypes. We additionally establish subtype-specific signatures that are able to identify a small proportion of pre-invasive tumors with expression profiles that resemble invasive carcinoma, indicating a higher likelihood of future disease progression.

  2. Estimation of age- and stage-specific Catalan breast cancer survival functions using US and Catalan survival data

    Science.gov (United States)

    2009-01-01

    Background During the last part of the 1990s the chance of surviving breast cancer increased. Changes in survival functions reflect a mixture of effects. Both, the introduction of adjuvant treatments and early screening with mammography played a role in the decline in mortality. Evaluating the contribution of these interventions using mathematical models requires survival functions before and after their introduction. Furthermore, required survival functions may be different by age groups and are related to disease stage at diagnosis. Sometimes detailed information is not available, as was the case for the region of Catalonia (Spain). Then one may derive the functions using information from other geographical areas. This work presents the methodology used to estimate age- and stage-specific Catalan breast cancer survival functions from scarce Catalan survival data by adapting the age- and stage-specific US functions. Methods Cubic splines were used to smooth data and obtain continuous hazard rate functions. After, we fitted a Poisson model to derive hazard ratios. The model included time as a covariate. Then the hazard ratios were applied to US survival functions detailed by age and stage to obtain Catalan estimations. Results We started estimating the hazard ratios for Catalonia versus the USA before and after the introduction of screening. The hazard ratios were then multiplied by the age- and stage-specific breast cancer hazard rates from the USA to obtain the Catalan hazard rates. We also compared breast cancer survival in Catalonia and the USA in two time periods, before cancer control interventions (USA 1975–79, Catalonia 1980–89) and after (USA and Catalonia 1990–2001). Survival in Catalonia in the 1980–89 period was worse than in the USA during 1975–79, but the differences disappeared in 1990–2001. Conclusion Our results suggest that access to better treatments and quality of care contributed to large improvements in survival in Catalonia. On

  3. Human Papilloma Viruses and Breast Cancer – Assessment of Causality

    Science.gov (United States)

    Lawson, James Sutherland; Glenn, Wendy K.; Whitaker, Noel James

    2016-01-01

    High risk human papilloma viruses (HPVs) may have a causal role in some breast cancers. Case–control studies, conducted in many different countries, consistently indicate that HPVs are more frequently present in breast cancers as compared to benign breast and normal breast controls (odds ratio 4.02). The assessment of causality of HPVs in breast cancer is difficult because (i) the HPV viral load is extremely low, (ii) HPV infections are common but HPV associated breast cancers are uncommon, and (iii) HPV infections may precede the development of breast and other cancers by years or even decades. Further, HPV oncogenesis can be indirect. Despite these difficulties, the emergence of new evidence has made the assessment of HPV causality, in breast cancer, a practical proposition. With one exception, the evidence meets all the conventional criteria for a causal role of HPVs in breast cancer. The exception is “specificity.” HPVs are ubiquitous, which is the exact opposite of specificity. An additional reservation is that the prevalence of breast cancer is not increased in immunocompromised patients as is the case with respect to HPV-associated cervical cancer. This indicates that HPVs may have an indirect causal influence in breast cancer. Based on the overall evidence, high-risk HPVs may have a causal role in some breast cancers. PMID:27747193

  4. MicroRNA-139 suppresses proliferation in luminal type breast cancer cells by targeting Topoisomerase II alpha

    Energy Technology Data Exchange (ETDEWEB)

    Hua, Wei [Department of Obstetrics and Gynecology, Xijing Hospital, Fourth Military Medical University, Xi' an 710032 (China); State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, 710032 Xi' an (China); Sa, Ke-Di; Zhang, Xiang; Jia, Lin-Tao; Zhao, Jing [State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, 710032 Xi' an (China); Yang, An-Gang [State Key Laboratory of Cancer Biology, Department of Immunology, Fourth Military Medical University, 710032 Xi' an (China); Zhang, Rui, E-mail: ruizhang@fmmu.edu.cn [State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, 710032 Xi' an (China); Fan, Jing, E-mail: jingfan@fmmu.edu.cn [Department of Vascular and Endocrine Surgery, Xijing Hospital, Fourth Military Medical University, Xi' an 710032 (China); Bian, Ka, E-mail: kakamax85@hotmail.com [State Key Laboratory of Cancer Biology, Department of Immunology, Fourth Military Medical University, 710032 Xi' an (China); Department of Otolaryngology, Tangdu Hospital, Fourth Military Medical University, Xi' an 710038 (China)

    2015-08-07

    The classification of molecular subtypes of breast cancer improves the prognostic accuracy and therapeutic benefits in clinic. However, because of the complexity of breast cancer, more biomarkers and functional molecules need to be explored. Here, analyzing the data in a huge cohort of breast cancer patients, we found that Topoisomerase II alpha (TOP2a), an important target of chemotherapy is a biomarker for prognosis in luminal type breast cancer patients, but not in basal like or HER2 positive breast cancer patients. We identified that miR-139, a previous reported anti-metastatic microRNA targets 3’-untranslated region (3′UTR) of TOP2a mRNA. Further more, we revealed that the forced expression of miR-139 reduces the TOP2a expression at both mRNA and protein levels. And our functional experiments showed that the ectopic expression of miR-139 remarkably inhibits proliferation in luminal type breast cancer cells, while exogenous TOP2a expression could rescue inhibition of cell proliferation mediated by miR-139. Collectively, our present study demonstrates the miR-139-TOP2a regulatory axis is important for proliferation in luminal type breast cancer cells. This functional link may help us to further understand the specificity of subtypes of breast cancer and optimize the strategy of cancer treatment. - Highlights: • High levels of TOP2a expression are closely associated with poor prognosis in luminal type breast cancer patients. • TOP2a is a novel target of miR-139. • Overexpression of miR-139 inhibits proliferation in luminal type breast cancer cells. • TOP2a is essential for miR-139-induced growth arrest in luminal type breast cancer cells.

  5. MicroRNA-139 suppresses proliferation in luminal type breast cancer cells by targeting Topoisomerase II alpha

    International Nuclear Information System (INIS)

    Hua, Wei; Sa, Ke-Di; Zhang, Xiang; Jia, Lin-Tao; Zhao, Jing; Yang, An-Gang; Zhang, Rui; Fan, Jing; Bian, Ka

    2015-01-01

    The classification of molecular subtypes of breast cancer improves the prognostic accuracy and therapeutic benefits in clinic. However, because of the complexity of breast cancer, more biomarkers and functional molecules need to be explored. Here, analyzing the data in a huge cohort of breast cancer patients, we found that Topoisomerase II alpha (TOP2a), an important target of chemotherapy is a biomarker for prognosis in luminal type breast cancer patients, but not in basal like or HER2 positive breast cancer patients. We identified that miR-139, a previous reported anti-metastatic microRNA targets 3’-untranslated region (3′UTR) of TOP2a mRNA. Further more, we revealed that the forced expression of miR-139 reduces the TOP2a expression at both mRNA and protein levels. And our functional experiments showed that the ectopic expression of miR-139 remarkably inhibits proliferation in luminal type breast cancer cells, while exogenous TOP2a expression could rescue inhibition of cell proliferation mediated by miR-139. Collectively, our present study demonstrates the miR-139-TOP2a regulatory axis is important for proliferation in luminal type breast cancer cells. This functional link may help us to further understand the specificity of subtypes of breast cancer and optimize the strategy of cancer treatment. - Highlights: • High levels of TOP2a expression are closely associated with poor prognosis in luminal type breast cancer patients. • TOP2a is a novel target of miR-139. • Overexpression of miR-139 inhibits proliferation in luminal type breast cancer cells. • TOP2a is essential for miR-139-induced growth arrest in luminal type breast cancer cells

  6. Effect of depression before breast cancer diagnosis on mortality among postmenopausal women.

    Science.gov (United States)

    Liang, Xiaoyun; Margolis, Karen L; Hendryx, Michael; Reeves, Katherine; Wassertheil-Smoller, Sylvia; Weitlauf, Julie; Danhauer, Suzanne C; Chlebowski, Rowan T; Caan, Bette; Qi, Lihong; Lane, Dorothy; Lavasani, Sayeh; Luo, Juhua

    2017-08-15

    Few previous studies investigating depression before the diagnosis of breast cancer and breast cancer-specific mortality have examined depression measured at more than 1 time point. This study investigated the effect of depression (combining depressive symptoms alone with antidepressant use) measured at 2 time points before the diagnosis of breast cancer on all-cause mortality and breast cancer-specific mortality among older postmenopausal women. A large prospective cohort, the Women's Health Initiative, was used. The study included 3095 women with incident breast cancer who had measures of depressive symptoms and antidepressant use before their diagnosis at the baseline and at year 3. Multivariate Cox proportional hazards regression was used to estimate adjusted hazard ratios (HRs) between depression at the baseline, depression at year 3, and combinations of depression at these time points and all-cause mortality and breast cancer-specific mortality. Depression at year 3 before a breast cancer diagnosis was associated with higher all-cause mortality after adjustments for multiple covariates (HR, 1.35; 95% confidence interval [CI], 1.02-1.78). There was no statistically significant association of baseline depression and all-cause mortality or breast cancer-specific mortality whether or not depression was also present at year 3. In women with late-stage (regional- or distant-stage) breast cancer, newly developed depression at year 3 was significantly associated with both all-cause mortality (HR, 2.00; 95% CI, 1.13-3.56) and breast cancer-specific mortality (HR, 2.42; 95% CI, 1.24-4.70). Women with newly developed depression before the diagnosis of breast cancer had a modestly but significantly increased risk for death from any cause and for death from breast cancer at a late stage. Cancer 2017;123:3107-15. © 2017 American Cancer Society. © 2017 American Cancer Society.

  7. Active smoking and survival following breast cancer among African American and non-African American women in the Carolina Breast Cancer Study.

    Science.gov (United States)

    Parada, Humberto; Sun, Xuezheng; Tse, Chiu-Kit; Olshan, Andrew F; Troester, Melissa A; Conway, Kathleen

    2017-09-01

    To examine racial differences in smoking rates at the time of breast cancer diagnosis and subsequent survival among African American and non-African American women in the Carolina Breast Cancer Study (Phases I/II), a large population-based North Carolina study. We interviewed 788 African American and 1,020 Caucasian/non-African American women diagnosed with invasive breast cancer from 1993 to 2000, to assess smoking history. After a median follow-up of 13.56 years, we identified 717 deaths using the National Death Index; 427 were breast cancer-related. We used Cox regression to examine associations between self-reported measures of smoking and breast cancer-specific survival within 5 years and up to 18 years after diagnosis conditional on 5-year survival. We examined race and estrogen receptor status as potential modifiers. Current (vs never) smoking was not associated with 5-year survival; however, risk of 13 year conditional breast cancer-specific mortality was elevated among women who were current smokers at diagnosis (HR 1.54, 95% CI 1.06-2.25), compared to never smokers. Although smoking rates were similar among African American (22.0%) and non-African American (22.1%) women, risk of breast cancer-specific mortality was elevated among African American (HR 1.69, 95% CI 1.00-2.85), but only weakly elevated among non-African American (HR 1.22, 95% CI 0.70-2.14) current (vs. never) smokers (P Interaction  = 0.30). Risk of breast cancer-specific mortality was also elevated among current (vs never) smokers diagnosed with ER - (HR 2.58, 95% CI 1.35-4.93), but not ER + (HR 1.11, 95% CI 0.69-1.78) tumors (P Interaction  = 0.17). Smoking may negatively impact long-term survival following breast cancer. Racial differences in long-term survival, as related to smoking, may be driven by ER status, rather than by differences in smoking patterns.

  8. Advanced generation anti-prostate specific membrane antigen designer T cells for prostate cancer immunotherapy.

    Science.gov (United States)

    Ma, Qiangzhong; Gomes, Erica M; Lo, Agnes Shuk-Yee; Junghans, Richard P

    2014-02-01

    Adoptive immunotherapy by infusion of designer T cells (dTc) engineered with chimeric antigen receptors (CARs) for tumoricidal activity represents a potentially highly specific modality for the treatment of cancer. In this study, 2nd generation (gen) anti-prostate specific membrane antigen (PSMA) dTc were developed for improving the efficacy of previously developed 1st gen dTc for prostate cancer immunotherapy. The 1st gen dTc are modified with chimeric immunoglobulin-T cell receptor (IgTCR) while the 2nd gen dTc are engineered with an immunoglobulin-CD28-T cell receptor (IgCD28TCR), which incorporates a CD28 costimulatory signal for optimal T cell activation. A 2nd gen anti-PSMA IgCD28TCR CAR was constructed by inserting the CD28 signal domain into the 1st gen CAR. 1st and 2nd gen anti-PSMA dTc were created by transducing human T cells with anti-PSMA CARs and their antitumor efficacy was compared for specific activation on PSMA-expressing tumor contact, cytotoxicity against PSMA-expressing tumor cells in vitro, and suppression of tumor growth in an animal model. The 2nd gen dTc can be optimally activated to secrete larger amounts of cytokines such as IL2 and IFNγ than 1st gen and to proliferate more vigorously on PSMA-expressing tumor contact. More importantly, the 2nd gen dTc preserve the PSMA-specific cytotoxicity in vitro and suppress tumor growth in animal models with significant higher potency. Our results demonstrate that 2nd gen anti-PSMA designer T cells exhibit superior antitumor functions versus 1st gen, providing a rationale for advancing this improved agent toward clinical application in prostate cancer immunotherapy. © 2013 Wiley Periodicals, Inc.

  9. Diagnostic value of dynamic and morphologic breast MRI analysis in the diagnosis of breast cancer

    International Nuclear Information System (INIS)

    Stusińska, Małgorzata; Szabo-Moskal, Jadwiga; Bobek-Billewicz, Barbara

    2014-01-01

    Mammography is the most widely used method of breast imaging. However, its low sensitivity poses a problem. Breast MRI is one of so the called “complementary” breast imaging methods. The purpose of this study was to improve the specificity of breast MRI by combining 2 methods: dynamic and morphologic analysis of enhancing lesions. 222 women aged 19–76 years, who underwent breast MRI examination between November 2002 and April 2004 at the Radiology Department of Oncology Center in Bydgoszcz, were included in this study. The pathological examination revealed cancer in 55 women (25%). No cancer was found in 167 women (75%), 56 of which were verified pathologically, 111 by cytology and/or during follow-up (at least 24 months). Results of breast MRI were positive in 80 women (36%), in 54 of which cancer was found during pathological examination, 26 breast MRI results were false positive. Sensitivity and specificity of breast MRI for dynamic analysis were 87% and 72%, respectively; in case of morphologic analysis 98% and 74%, respectively. The combined dynamic and morphologic analysis achieved high (84%) specificity without loss of sensitivity (98%). The difference in specificity between the evaluated methods was statistically significant (p<0.05). The combined dynamic and morphologic breast MRI analysis is a useful method for the diagnosis of breast cancer

  10. Stages of Breast Cancer

    Science.gov (United States)

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

  11. Functional Time Series Models to Estimate Future Age-Specific Breast Cancer Incidence Rates for Women in Karachi, Pakistan

    Institute of Scientific and Technical Information of China (English)

    Farah Yasmeen[1; Sidra Zaheer[2

    2014-01-01

    Background: Breast cancer is the most common female cancer in Pakistan. The incidence of breast cancer in Pakistan is about 2.5 times higher than that in the neighboring countries India and Iran. In Karachi, the most populated city of Pakistan, the age-standardized rate of breast cancer was 69.1 per 100,000 women during 1998-2002, which is the highest recorded rate in Asia. The carcinoma of breast in Pakistan is an enormous public health concern. In this study, we examined the recent trends of breast cancer incidence rates among the women in Karachi. Methods: We obtained the secondary data of breast cancer incidence from various hospitals. They included Jinnah Hospital, KIRAN (Karachi Institute of Radiotherapy and Nuclear Medicine), and Civil hospital, where the data were available for the years 2004-2011. A total of 5331 new cases of female breast cancer were registered during this period. We analyzed the data in 5-year age groups 15-19, 20-24, 25-29, 30-34, 35-39, 40-44, 45-49, 50-54, 55-59, 60-64, 65-69, 70-74, 75+. Nonparametric smoothing were used to obtained age-specific incidence curves, and then the curves are decomposed using principal components analysis to fit FTS (functional time series) model. We then used exponential smoothing statspace models to estimate the forecasts of incidence curve and construct prediction intervals. Results: The breast cancer incidence rates in Karachi increased with age for all available years. The rates increased monotonically and are relatively sharp with the age from 15 years to 50 years and then they show variability after the age of 50 years. 10-year forecasts for the female breast cancer incidence rates in Karachi show that the future rates are expected to remain stable for the age-groups 15-50 years, but they will increase for the females of 50-years and over. Hence in future, the newly diagnosed breast cancer cases in the older women in Karachi are expected to increase. Conclusion: Prediction of age

  12. Separation of breast cancer cells from peripherally circulating blood using antibodies fixed in microchannels

    Science.gov (United States)

    Feng, Juan; Soper, Steven A.; McCarley, Robin L.; Murphy, Michael C.

    2004-07-01

    Bio-Micro Electro Mechanical System (Bio-MEMS) technology was applied to the problem of early breast cancer detection and diagnosis. A micro-device is being developed to identify and specifically collect tumor cells of low abundance (1 tumor cell among 107 normal blood cells) from circulating whole blood. By immobilizing anti-EpCAM (Epithelial Cell Adhesion Molecule) antibodies on polymer micro-channel walls by chemically modifying the surface of the PMMA, breast cancer cells from the MCF-7 cell line, which over-express EpCAM, were selected from a sample volume by the strong binding affinity between the antibody and antigen. To validate the capture of the breast cancer cells, three fluorochrome markers, each identified by a separate color, were used to reliably identify the cancer cells. The cancer cells were defined by DAPI+ (blue), CD45- and the FITC-cell membrane linker+ (green). White blood cells, which may interfere in the detection of the cancer cells, were identified by DAPI+ (blue), CD45+ (red), and the FITC-cell membrane linker+ (green). EpCAM/anti-EpCAM binding models from the literature were used to estimate an optimal velocity, 2mm/sec, for maximizing the number of cells binding and the critical binding force. At higher velocities, shear forces (> 0.48 dyne) will break existing bonds and prevent the formation of new ones. This detection micro-device can be assembled with other lab-on-a-chip components for follow-up gene and protein analysis.

  13. Radiographic characteristics of male breast cancer

    International Nuclear Information System (INIS)

    Kim, Tae Hoon; Kim, Ji Hyung; Oh, Ki Keun; Park, Chang Yun; Kook, Shin Ho

    1995-01-01

    Our objective was to evaluate mammographic findings of breast cancer in men. This study includes 9 man with breast cancer diagnosed pathologically by radical mastectomy. Clinical and pathologic data were obtained by review of patients medical record. Mammograms were analyzed retrospectively. Of the 9 patients, eight had masses with spiculated margin or schirrous pattern with irregular margin. One patient had no specific evidence of breast cancer mammographically. Microcalcifications were seen in three patients, these calcifications were irregular in shape and were clustered. Of the 8 cases, four patients had the masses at the right breast, four at the left breast. Locations of breast cancer were subareolar (n=4) and were eccentric (n=4) from the nipple. The most common location was the upper outer quadrant. On histologic evaluation, 7 cases were infiltrating ductal carcinomas, one case was mucinous adenocarcinoma, and the remainder was proved as combined form of intraductal and infiltrating ductal carcinoma. Axillary lymph node metastasis were found in 4 cases. Mammographic findings of male breast carcinoma were that of subareolar or eccentrically located mass. Calcifications were same to the patterns of calcification as female breast cancer

  14. Understanding drugs in breast cancer through drug sensitivity screening.

    Science.gov (United States)

    Uhr, Katharina; Prager-van der Smissen, Wendy J C; Heine, Anouk A J; Ozturk, Bahar; Smid, Marcel; Göhlmann, Hinrich W H; Jager, Agnes; Foekens, John A; Martens, John W M

    2015-01-01

    With substantial numbers of breast tumors showing or acquiring treatment resistance, it is of utmost importance to develop new agents for the treatment of the disease, to know their effectiveness against breast cancer and to understand their relationships with other drugs to best assign the right drug to the right patient. To achieve this goal drug screenings on breast cancer cell lines are a promising approach. In this study a large-scale drug screening of 37 compounds was performed on a panel of 42 breast cancer cell lines representing the main breast cancer subtypes. Clustering, correlation and pathway analyses were used for data analysis. We found that compounds with a related mechanism of action had correlated IC50 values and thus grouped together when the cell lines were hierarchically clustered based on IC50 values. In total we found six clusters of drugs of which five consisted of drugs with related mode of action and one cluster with two drugs not previously connected. In total, 25 correlated and four anti-correlated drug sensitivities were revealed of which only one drug, Sirolimus, showed significantly lower IC50 values in the luminal/ERBB2 breast cancer subtype. We found expected interactions but also discovered new relationships between drugs which might have implications for cancer treatment regimens.

  15. Progestins in the menopause in healthy women and breast cancer patients.

    Science.gov (United States)

    Pasqualini, Jorge R

    2009-04-20

    At present, more than 200 progestin compounds are synthetized, but their biological effects are different: this is function of their structure, receptor affinity, metabolic transformations, the target tissues considered, dose. The action of progestins in breast cancer is controversial; some studies indicate an increase in breast cancer incidence, others show no differences, and yet others indicate a decrease. Many studies agree that treatment with progestins plus estrogens at a low dose and during a limited period (less than 5 years) can have beneficial effects in peri- and post-menopausal women. It was demonstrated that various progestins (e.g. nomegestrol acetate, medrogestone, promegestone), as well as tibolone and its metabolites, can block the enzymes involved in estradiol bioformation (sulfatase, 17beta-hydroxysteroid dehydrogenase) in breast cancer. Progesterone is converted into various metabolic products: in normal breast tissue the transformation is mainly to 4-ene derivatives, whereas in the tumor tissue 5alpha-pregane derivatives are predominant. Aromatase activity is the last step in the formation of estrogens by the conversion of androgens. In recent studies it was shown that 20alpha-dihydroprogesterone, a metabolite found mainly in normal breast tissue and having anti-proliferative properties, can act as an anti-aromatase agent. The data suggest the possible utilization of this compound in breast cancer prevention. In conclusion, in order to clarify and better understand the response of progestins in breast cancer (incidence and mortality), as well as in hormone replacement therapy or in endocrine dysfunction, new clinical trials are necessary using other progestins in function of the dose and period of treatment.

  16. False-positive findings in mammography screening induces short-term distress - breast cancer-specific concern prevails longer

    DEFF Research Database (Denmark)

    Aro, A R; Pilvikki Absetz, S; van Elderen, T M

    2000-01-01

    -ups at 2 and 12 months postscreening. At 2 months, there was a moderate multivariate effect of group on distress; and intrusive thinking and worry about breast cancer, in particular, were most frequent amongst the false positives. Intrusive thinking still prevailed at 12 months, in addition to a higher...... findings (n=1407), false-positive findings (n=492) and referents from outside the screening programme (n=1718, age 48-49 years). Distress was measured as illness worry, anxiety, depression, cancer beliefs and early detection behaviour. Measurements were one month before screening invitation with follow...... perceived breast cancer risk and susceptibility. Distress related to screening and false-positive findings seems to be moderate, but prevailing cancer-specific concerns call for improvements in screening programmes....

  17. Profile of thyroid hormones in breast cancer patients

    Directory of Open Access Journals (Sweden)

    P.P. Saraiva

    2005-05-01

    Full Text Available Estrogen involvement in breast cancer has been established; however, the association between breast cancer and thyroid diseases is controversial. Estrogen-like effects of thyroid hormone on breast cancer cell growth in culture have been reported. The objective of the present study was to determine the profile of thyroid hormones in breast cancer patients. Serum aliquots from 26 patients with breast cancer ranging in age from 30 to 85 years and age-matched normal controls (N = 22 were analyzed for free triiodothyronine (T3F, free thyroxine (T4F, thyroid-stimulating hormone (TSH, antiperoxidase antibody (TPO, and estradiol (E2. Estrogen receptor ß (ERß was determined in tumor tissues by immunohistochemistry. Thyroid disease incidence was higher in patients than in controls (58 vs 18%, P < 0.05. Subclinical hyperthyroidism was the most frequent disorder in patients (31%; hypothyroidism (8% and positive anti-TPO antibodies (19% were also found. Subclinical hypothyroidism was the only dysfunction (18% found in controls. Hyperthyroidism was associated with postmenopausal patients, as shown by significantly higher mean T3 and T4 values and lower TSH levels in this group of breast cancer patients than in controls. The majority of positive ERß tumors were clustered in the postmenopausal patients and all cases presenting subclinical hyperthyroidism in this subgroup concomitantly exhibited Erß-positive tumors. Subclinical hyperthyroidism was present in only one of 6 premenopausal patients. We show here that postmenopausal breast cancer patients have a significantly increased thyroid hormone/E2 ratio (P < 0.05, suggesting a possible tumor growth-promoting effect caused by this misbalance.

  18. Breast cancer

    Science.gov (United States)

    ... can help you know how to prevent breast cancer. Breast implants, using antiperspirants, and wearing underwire bras do not increase the risk for breast cancer. There is also no evidence of a direct ...

  19. Equol enhances tamoxifen’s anti-tumor activity by induction of caspase-mediated apoptosis in MCF-7 breast cancer cells

    International Nuclear Information System (INIS)

    Charalambous, Christiana; Pitta, Chara A; Constantinou, Andreas I

    2013-01-01

    Soy phytoestrogens, such as daidzein and its metabolite equol, have been proposed to be responsible for the low breast cancer rate in Asian women. Since the majority of estrogen receptor positive breast cancer patients are treated with tamoxifen, the basic objective of this study is to determine whether equol enhances tamoxifen’s anti-tumor effect, and to identify the molecular mechanisms involved. For this purpose, we examined the individual and combined effects of equol and tamoxifen on the estrogen-dependent MCF-7 breast cancer cells using viability assays, annexin-V/PI staining, cell cycle and western blot analysis. We found that equol (>50 μM) and 4-hydroxy-tamoxifen (4-OHT; >100 nM) significantly reduced the MCF-7 cell viability. Furthermore, the combination of equol (100 μM) and 4-OHT (10 μM) induced apoptosis more effectively than each compound alone. Subsequent treatment of MCF-7 cells with the pan-caspase inhibitor Z-VAD-FMK inhibited equol- and 4-OHT-mediated apoptosis, which was accompanied by PARP and α-fodrin cleavage, indicating that apoptosis is mainly caspase-mediated. These compounds also induced a marked reduction in the bcl-2:bax ratio, which was accompanied by caspase-9 and caspase-7 activation and cytochrome-c release to the cytosol. Taken together, these data support the notion that the combination of equol and tamoxifen activates the intrinsic apoptotic pathway more efficiently than each compound alone. Consequently, equol may be used therapeutically in combination treatments and clinical studies to enhance tamoxifen’s effect by providing additional protection against estrogen-responsive breast cancers

  20. Advancements of antisense oligonucleotides in treatment of breast cancer

    Institute of Scientific and Technical Information of China (English)

    YANGShuan-Ping; SONGSan-Tai; 等

    2003-01-01

    Breast cancer is one kind of multi-gene related malignancy.Overexpression of some oncogenes such as HER-2(c-erbB-2,Neu),bcl-2/bcl-xL,protein kinase A(PKA),and transferrin receptor gene(TfR gene),etc significantly affect the prognosis of breast cancer.It was shown that specific suppression of the overexpressed genes above resulted in the improvement of the therapy of breast cancer.Antisense interference.one of useful tools for inhibiting the overexpression of specific oncogenes,was involved in the therapy of breast cancer in recent years. Data indicated that antisense oligonucleotides(ON)could inhibit specially the expression of the target genes on mRNA or protein levels in most of cases;some ON candidates showed encouraging therapeutic effects in vitro and in vivo on breast cancer cell lines or xenografts.Furthermore,the combination use of the antisense ON and normal chemotherapeutic agents indicated synergistic antitumor effects,which was probably the best utilization of antisense ON in the treatment of breast cancer.

  1. Breast Cancer: Treatment Options

    Science.gov (United States)

    ... Breast Cancer > Breast Cancer: Treatment Options Request Permissions Breast Cancer: Treatment Options Approved by the Cancer.Net Editorial ... can be addressed as quickly as possible. Recurrent breast cancer If the cancer does return after treatment for ...

  2. Screening for breast cancer in a high-risk series

    International Nuclear Information System (INIS)

    Woodard, E.D.; Hempelmann, L.H.; Janus, J.; Logan, W.; Dean, P.

    1982-01-01

    A unique cohort of women at increased risk of breast cancer because of prior X-ray treatment of acute mastitis and their selected high-risk siblings were offered periodic breast cancer screening including physical examination of the breasts, mammography, and thermography. Twelve breast cancers were detected when fewer than four would have been expected based on age-specific breast cancer detection rates from the National Cancer institute/American Cancer Society Breast Cancer Demonstration Detection Projects. Mammograpy was positive in all cases but physical examination was positive in only three cases. Thermography was an unreliable indicator of disease. Given the concern over radiation-induced risk, use of low-dose technique and of criteria for participation that select women at high risk of breast cancer will maximize the benefit/risk ratio for mammography screening

  3. Activity of the kinesin spindle protein inhibitor ispinesib (SB-715992) in models of breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Purcell, James W; Davis, Jefferson; Reddy, Mamatha; Martin, Shamra; Samayoa, Kimberly; Vo, Hung; Thomsen, Karen; Bean, Peter; Kuo, Wen Lin; Ziyad, Safiyyah; Billig, Jessica; Feiler, Heidi S; Gray, Joe W; Wood, Kenneth W; Cases, Sylvaine

    2009-06-10

    Ispinesib (SB-715992) is a potent inhibitor of kinesin spindle protein (KSP), a kinesin motor protein essential for the formation of a bipolar mitotic spindle and cell cycle progression through mitosis. Clinical studies of ispinesib have demonstrated a 9% response rate in patients with locally advanced or metastatic breast cancer, and a favorable safety profile without significant neurotoxicities, gastrointestinal toxicities or hair loss. To better understand the potential of ispinesib in the treatment of breast cancer we explored the activity of ispinesib alone and in combination several therapies approved for the treatment of breast cancer. We measured the ispinesib sensitivity and pharmacodynamic response of breast cancer cell lines representative of various subtypes in vitro and as xenografts in vivo, and tested the ability of ispinesib to enhance the anti-tumor activity of approved therapies. In vitro, ispinesib displayed broad anti-proliferative activity against a panel of 53 breast cell-lines. In vivo, ispinesib produced regressions in each of five breast cancer models, and tumor free survivors in three of these models. The effects of ispinesib treatment on pharmacodynamic markers of mitosis and apoptosis were examined in vitro and in vivo, revealing a greater increase in both mitotic and apoptotic markers in the MDA-MB-468 model than in the less sensitive BT-474 model. In vivo, ispinesib enhanced the anti-tumor activity of trastuzumab, lapatinib, doxorubicin, and capecitabine, and exhibited activity comparable to paclitaxel and ixabepilone. These findings support further clinical exploration of KSP inhibitors for the treatment of breast cancer.

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

    Science.gov (United States)

    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

  5. Anti-Podocalyxin Monoclonal Antibody 47-mG2a Detects Lung Cancers by Immunohistochemistry.

    Science.gov (United States)

    Yamada, Shinji; Itai, Shunsuke; Kaneko, Mika K; Kato, Yukinari

    2018-04-01

    Lung cancer is one of the leading causes of cancer-related deaths in the world. Regardless of the advances in lung cancer treatments, the prognosis is still poor. Podocalyxin (PODXL) is a highly glycosylated type I transmembrane protein that is expressed in normal tissues, including the heart, pancreas, and breast. It is also found and used as a diagnostic marker in many cancers, such as renal, brain, breast, oral, and lung cancers. We previously developed specific and sensitive anti-PODXL monoclonal antibodies, PcMab-47 (mouse IgG 1 , kappa) and its mouse IgG 2a -type (47-mG 2a ), both of which were suitable for immunohistochemical analyses of oral cancers. In this study, we investigated the utility of PcMab-47 and 47-mG 2a for the immunohistochemical analyses of lung cancers. PcMab-47 stained 51/70 (72.9%) cases of lung cancer, whereas 47-mG 2a stained 59/70 (84.3%) cases, indicating that the latter antibody is more sensitive and is useful for detecting PODXL in lung cancers.

  6. Breast Cancer Screening

    International Nuclear Information System (INIS)

    Altaf, Fadwa J.

    2004-01-01

    Breast cancer is a very common health problem in Saudi females that can be reduced by early detection through introducing breast cancer screening. Literature review reveals significant reduction in breast cancer incidence and outcome after the beginning of breast cancer screening. The objectives of this article are to highlight the significance of breast cancer screening in different international societies and to write the major guidelines of breast cancer screening in relation to other departments involved with more emphasis on the Pathology Department guidelines in tissue handling, diagnostic criteria and significance of the diagnosis. This article summaries and acknowledges major work carried out before, and recommends similar modified work in order to meet the requirement for the Saudi society. (author)

  7. Sexuality after breast cancer: cultural specificities of Tunisian ...

    African Journals Online (AJOL)

    The objectives of this study were to evaluate the changes in sexual life after treatment of ... to be involved in sexual satisfaction of Tunisian women after breast cancer. ... counseling to maintain and enhance patient's psychological well-being.

  8. Methylation of Breast Cancer Predisposition Genes in Early-Onset Breast Cancer: Australian Breast Cancer Family Registry.

    Directory of Open Access Journals (Sweden)

    Cameron M Scott

    Full Text Available DNA methylation can mimic the effects of both germline and somatic mutations for cancer predisposition genes such as BRCA1 and p16INK4a. Constitutional DNA methylation of the BRCA1 promoter has been well described and is associated with an increased risk of early-onset breast cancers that have BRCA1-mutation associated histological features. The role of methylation in the context of other breast cancer predisposition genes has been less well studied and often with conflicting or ambiguous outcomes. We examined the role of methylation in known breast cancer susceptibility genes in breast cancer predisposition and tumor development. We applied the Infinium HumanMethylation450 Beadchip (HM450K array to blood and tumor-derived DNA from 43 women diagnosed with breast cancer before the age of 40 years and measured the methylation profiles across promoter regions of BRCA1, BRCA2, ATM, PALB2, CDH1, TP53, FANCM, CHEK2, MLH1, MSH2, MSH6 and PMS2. Prior genetic testing had demonstrated that these women did not carry a germline mutation in BRCA1, ATM, CHEK2, PALB2, TP53, BRCA2, CDH1 or FANCM. In addition to the BRCA1 promoter region, this work identified regions with variable methylation at multiple breast cancer susceptibility genes including PALB2 and MLH1. Methylation at the region of MLH1 in these breast cancers was not associated with microsatellite instability. This work informs future studies of the role of methylation in breast cancer susceptibility gene silencing.

  9. Hyaluronan-conjugated liposomes encapsulating gemcitabine for breast cancer stem cells

    Directory of Open Access Journals (Sweden)

    Han NK

    2016-04-01

    Full Text Available Na-Kyung Han,1,* Dae Hwan Shin,1,* Jung Seok Kim,1 Kwon Yeon Weon,2 Chang-Young Jang,1 Jin-Seok Kim1 1Research Center for Cell Fate Control (RCCFC and College of Pharmacy, Sookmyung Women’s University, Seoul, 2College of Pharmacy, Catholic University of Daegu, Gyeongbuk, Korea *These authors contributed equally to this work Abstract: Investigation of potential therapeutics for targeting breast cancer stem cells (BCSCs is important because these cells are regarded as culprit of breast cancer relapse. Accomplishing this kind of strategy requires a specific drug-delivery system using the distinct features of liposomes. Studies on targeted liposomal delivery systems have indicated the conjugation of hyaluronan (HA, a primary ligand for CD44 surface markers, as an appropriate method for targeting BCSCs. For this study, enriched BCSCs were obtained by culturing MCF-7 breast cancer cells in nonadherent conditions. The enriched BCSCs were challenged with HA-conjugated liposomes encapsulating gemcitabine (2, 2-difluoro-2-deoxycytidine, GEM. In vitro study showed that the HA-conjugated liposomes significantly enhanced the cytotoxicity, anti-migration, and anti-colony formation abilities of GEM through targeting of CD44 expressed on BCSCs. In pharmacokinetic study, area under the drug concentration vs time curve (AUC of the immunoliposomal GEM was 3.5 times higher than that of free GEM, indicating that the HA-conjugated liposomes enhanced the stability of GEM in the bloodstream and therefore prolonged its half-life time. The antitumor effect of the immunoliposomal GEM was 3.3 times higher than that of free GEM in a xenograft mouse model, probably reflecting the unique targeting of the CD44 receptor by HA and the increased cytotoxicity and stability through the liposomal formulation. Furthermore, marginal change in body weight demonstrated that the use of liposomes considerably reduced the systemic toxicity of GEM on normal healthy cells. Taken together

  10. Herceptin Enhances the Antitumor Effect of Natural Killer Cells on Breast Cancer Cells Expressing Human Epidermal Growth Factor Receptor-2

    Directory of Open Access Journals (Sweden)

    Xiao Tian

    2017-10-01

    Full Text Available Optimal adoptive cell therapy (ACT should contribute to effective cancer treatment. The unique ability of natural killer (NK cells to kill cancer cells independent of major histocompatibility requirement makes them suitable as ACT tools. Herceptin, an antihuman epidermal growth factor receptor-2 (anti-HER2 monoclonal antibody, is used to treat HER2+ breast cancer. However, it has limited effectiveness and possible severe cardiotoxicity. Given that Herceptin may increase the cytotoxicity of lymphocytes, we explored the possible augmentation of NK cell cytotoxicity against HER2+ breast cancer cells by Herceptin. We demonstrated that Herceptin could interact with CD16 on NK cells to expand the cytotoxic NK (specifically, CD56dim cell population. Additionally, Herceptin increased NK cell migration and cytotoxicity against HER2+ breast cancer cells. In a pilot study, Herceptin-treated NK cells shrunk lung nodular metastasis in a woman with HER2+ breast cancer who could not tolerate the cardiotoxic side effects of Herceptin. Our findings support the therapeutic potential of Herceptin-treated NK cells in patients with HER2+ and Herceptin-intolerant breast cancer.

  11. Divergent oestrogen receptor-specific breast cancer trends in Ireland (2004-2013): Amassing data from independent Western populations provide etiologic clues.

    Science.gov (United States)

    Mullooly, Maeve; Murphy, Jeanne; Gierach, Gretchen L; Walsh, Paul M; Deady, Sandra; Barron, Thomas I; Sherman, Mark E; Rosenberg, Philip S; Anderson, William F

    2017-11-01

    The aetiology and clinical behaviour of breast cancers vary by oestrogen receptor (ER) expression, HER2 expression and over time. Data from the United States and Denmark show rising incidence rates for ER+ and falling incidence rates for ER- breast cancers. Given that Ireland is a somewhat similar Western population but with distinctive risk exposures (especially for lactation), we analysed breast cancer trends by ER status; and for the first time, by the joint expression of ER±/HER2±. We assessed invasive breast cancers (n = 24,845; 2004-2013) within the population-based National Cancer Registry of Ireland. The population at risk was obtained from the Irish Central Statistics Office (n = 10,401,986). After accounting for missing ER and HER2 data, we assessed receptor-specific secular trends in age-standardised incidence rates (ASRs) with the estimated annual percentage change (EAPC) and corresponding 95% confidence intervals (95% CI). Age-period-cohort models were also fitted to further characterise trends accounting for age, calendar-period and birth-cohort interactions. ASRs increased for ER+ (EAPC: 2.2% per year [95% CI: 0.97, 3.45%/year]) and decreased for ER- cancers (EAPC: -3.43% per year [95% CI: -5.05, -1.78%/year]), as well as for specific age groups at diagnosis (rates among independent Western populations likely reflects calendar-period and/or risk factor changes with differential effects for ER+ and ER- breast cancers. Published by Elsevier Ltd.

  12. Overview of the trastuzumab (Herceptin) anti-HER2 monoclonal antibody clinical program in HER2-overexpressing metastatic breast cancer. Herceptin Multinational Investigator Study Group.

    Science.gov (United States)

    Shak, S

    1999-08-01

    The recombinant humanized anti-HER2 monoclonal antibody trastuzumab (Herceptin; Genentech, San Francisco, CA) was evaluated in human clinical trials for treatment of women with metastatic breast cancer who have tumors that overexpress HER2. The trastuzumab clinical program consisted of a series of phase I, phase II, and phase III clinical trials. Clinical experience with this novel biologic has been obtained in more than 1,000 women with HER2-overexpressing metastatic breast cancer. Two pivotal trials were performed to evaluate trastuzumab efficacy and safety: (1) trastuzumab in combination with chemotherapy as first-line therapy and (2) trastuzumab as a single agent in second- and third-line chemotherapy. Preliminary results of the pivotal clinical trials that have been presented at national meetings are summarized below. The data suggest that trastuzumab will be an important new treatment option for women with HER2-overexpressing metastatic breast cancer.

  13. Breast cancer lung metastasis: Molecular biology and therapeutic implications.

    Science.gov (United States)

    Jin, Liting; Han, Bingchen; Siegel, Emily; Cui, Yukun; Giuliano, Armando; Cui, Xiaojiang

    2018-03-26

    Distant metastasis accounts for the vast majority of deaths in patients with cancer. Breast cancer exhibits a distinct metastatic pattern commonly involving bone, liver, lung, and brain. Breast cancer can be divided into different subtypes based on gene expression profiles, and different breast cancer subtypes show preference to distinct organ sites of metastasis. Luminal breast tumors tend to metastasize to bone while basal-like breast cancer (BLBC) displays a lung tropism of metastasis. However, the mechanisms underlying this organ-specific pattern of metastasis still remain to be elucidated. In this review, we will summarize the recent advances regarding the molecular signaling pathways as well as the therapeutic strategies for treating breast cancer lung metastasis.

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

    Science.gov (United States)

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

    2015-09-01

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

  15. Tannic Acid Preferentially Targets Estrogen Receptor-Positive Breast Cancer

    Directory of Open Access Journals (Sweden)

    Brian W. Booth

    2013-01-01

    Full Text Available Research efforts investigating the potential of natural compounds in the fight against cancer are growing. Tannic acid (TA belongs to the class of hydrolysable tannins and is found in numerous plants and foods. TA is a potent collagen cross-linking agent; the purpose of this study was to generate TA-cross-linked beads and assess the effects on breast cancer cell growth. Collagen beads were stable at body temperature following crosslinking. Exposure to collagen beads with higher levels of TA inhibited proliferation and induced apoptosis in normal and cancer cells. TA-induced apoptosis involved activation of caspase 3/7 and caspase 9 but not caspase 8. Breast cancer cells expressing the estrogen receptor were more susceptible to the effects of TA. Taken together the results suggest that TA has the potential to become an anti-ER+ breast cancer treatment or preventative agent.

  16. The Application of Non-Invasive Apoptosis Detection Sensor (NIADS on Histone Deacetylation Inhibitor (HDACi-Induced Breast Cancer Cell Death

    Directory of Open Access Journals (Sweden)

    Kai-Wen Hsu

    2018-02-01

    Full Text Available Breast cancer is the most common malignancy in women and the second leading cause of cancer death in women. Triple negative breast cancer (TNBC subtype is a breast cancer subset without ER (estrogen receptor, PR (progesterone receptor and HER2 (human epidermal growth factor receptor 2 expression, limiting treatment options and presenting a poorer survival rate. Thus, we investigated whether histone deacetylation inhibitor (HDACi could be used as potential anti-cancer therapy on breast cancer cells. In this study, we found TNBC and HER2-enriched breast cancers are extremely sensitive to Panobinostat, Belinostat of HDACi via experiments of cell viability assay, apoptotic marker identification and flow cytometry measurement. On the other hand, we developed a bioluminescence-based live cell non-invasive apoptosis detection sensor (NIADS detection system to evaluate the quantitative and kinetic analyses of apoptotic cell death by HDAC treatment on breast cancer cells. In addition, the use of HDACi may also contribute a synergic anti-cancer effect with co-treatment of chemotherapeutic agent such as doxorubicin on TNBC cells (MDA-MB-231, but not in breast normal epithelia cells (MCF-10A, providing therapeutic benefits against breast tumor in the clinic.

  17. Age-specific interval breast cancers in Japan. Estimation of the proper sensitivity of screening using a population-based cancer registry

    International Nuclear Information System (INIS)

    Suzuki, Akihiko; Kuriyama, Shinichi; Kawai, Masaaki

    2008-01-01

    The age-specific sensitivity of a screening program was investigated using a population-based cancer registry as a source of false-negative cancer cases. A population-based screening program for breast cancer was run using either clinical breast examinations (CBE) alone or mammography combined with CBE in the Miyagi Prefecture from 1997 to 2002. Interval cancers were newly identified by linking the screening records to the population-based cancer registry to estimate the number of false-negative cases of screening program. Among 112071 women screened by mammography combined with CBE, the number of detected cancers, false-negative cases and the sensitivity were 289, 22 and 92.9%, respectively, based on the reports from participating municipalities. The number of newly found false-negative cases and corrected sensitivity when using the registry were 34 and 83.8%, respectively. In detected cancers, the sensitivity of screening by mammography combined with CBE in women ranging from 40 to 49 years of age based on a population-based cancer registry was much lower than that in women 50-59 and 60-69 years of age (40-49: 18, 71.4%, 50-59: 19, 85.8%, 60-69: 19, 87.2%). These data suggest that the accurate outcome of an evaluation of breast cancer screening must include the use of a population-based cancer registry for detecting false-negative cases. Screening by mammography combined with CBE may therefore not be sufficiently sensitive for women ranging from 40 to 49 years of age. (author)

  18. Prognosis for Survival of Young Women with Breast Cancer by Quantitative p53 Immunohistochemistry

    Science.gov (United States)

    Axelrod, David E.; Shah, Kinsuk; Yang, Qifeng; Haffty, Bruce G.

    2015-01-01

    p53 protein detected immunohistochemically has not been accepted as a biomarker for breast cancer patients because of disparate reports of the relationship between the amount of p53 protein detected and patient survival. The purpose of this study was to determine experimental conditions and methods of data analysis for which p53 stain intensity could be prognostic for survival of young breast cancer patients. A tissue microarray of specimens from 93 patients was stained with anti-p53 antibody, and stain intensity measured with a computer-aided image analysis system. A cut-point at one standard deviation below the mean of the distribution of p53 stain intensity separated patients into two groups with significantly different survival. These results were confirmed by Quantitative Nuclear Grade determined by DNA-specific Feulgen staining. P53 provided information beyond ER and PR status. Therefore, under the conditions reported here, p53 protein can be an effective prognostic factor for young breast cancer patients. PMID:26322145

  19. Systematic drug screening reveals specific vulnerabilities and co-resistance patterns in endocrine-resistant breast cancer

    International Nuclear Information System (INIS)

    Kangaspeska, Sara; Hultsch, Susanne; Jaiswal, Alok; Edgren, Henrik; Mpindi, John-Patrick; Eldfors, Samuli; Brück, Oscar; Aittokallio, Tero; Kallioniemi, Olli

    2016-01-01

    The estrogen receptor (ER) inhibitor tamoxifen reduces breast cancer mortality by 31 % and has served as the standard treatment for ER-positive breast cancers for decades. However, 50 % of advanced ER-positive cancers display de novo resistance to tamoxifen, and acquired resistance evolves in 40 % of patients who initially respond. Mechanisms underlying resistance development remain poorly understood and new therapeutic opportunities are urgently needed. Here, we report the generation and characterization of seven tamoxifen-resistant breast cancer cell lines from four parental strains. Using high throughput drug sensitivity and resistance testing (DSRT) with 279 approved and investigational oncology drugs, exome-sequencing and network analysis, we for the first time, systematically determine the drug response profiles specific to tamoxifen resistance. We discovered emerging vulnerabilities towards specific drugs, such as ERK1/2-, proteasome- and BCL-family inhibitors as the cells became tamoxifen-resistant. Co-resistance to other drugs such as the survivin inhibitor YM155 and the chemotherapeutic agent paclitaxel also occurred. This study indicates that multiple molecular mechanisms dictate endocrine resistance, resulting in unexpected vulnerabilities to initially ineffective drugs, as well as in emerging co-resistances. Thus, combatting drug-resistant tumors will require patient-tailored strategies in order to identify new drug vulnerabilities, and to understand the associated co-resistance patterns. The online version of this article (doi:10.1186/s12885-016-2452-5) contains supplementary material, which is available to authorized users

  20. Breast density does not impact the ability of Videssa® Breast to detect breast cancer in women under age 50.

    Directory of Open Access Journals (Sweden)

    David E Reese

    Full Text Available Breast density is associated with reduced imaging resolution in the detection of breast cancer. A biochemical approach that is not affected by density would provide an important tool to healthcare professionals who are managing women with dense breasts and suspicious imaging findings. Videssa® Breast is a combinatorial proteomic biomarker assay (CPBA, comprised of Serum Protein Biomarkers (SPB and Tumor Associated Autoantibodies (TAAb integrated with patient-specific clinical data to produce a diagnostic score that reliably detects breast cancer (BC as an adjunctive tool to imaging. The performance of Videssa® Breast was evaluated in the dense (a and b and non-dense (c and d groups in a population of n = 545 women under age 50. The sensitivity and specificity in the dense breast group were calculated to be 88.9% and 81.2%, respectively, and 92.3% and 86.6%, respectively, for the non-dense group. No significant differences were observed in the sensitivity (p = 1.0 or specificity (p = 0.18 between these groups. The NPV was 99.3% and 99.1% in non-dense and dense groups, respectively. Unlike imaging, Videssa® Breast does not appear to be impacted by breast density; it can effectively detect breast cancer in women with dense and non-dense breasts alike. Thus, Videssa® Breast provides a powerful tool for healthcare providers when women with dense breasts present with challenging imaging findings. In addition, Videssa® Breast provides assurance to women with dense breasts that they do not have breast cancer, reducing further anxiety in this higher risk patient population.

  1. Physical activity influences the immune system of breast cancer patients

    Directory of Open Access Journals (Sweden)

    Thorsten Schmidt

    2017-01-01

    Full Text Available It has been suggested that physical activity in breast cancer patients can not only improve quality of life. Influences on physical and psychological levels have been evaluated, but effects on the immune system of breast cancer patients are hardly known. A PubMed search identified relevant trials and meta-analyses from 1970 to 2013. This review summarizes the results of international studies and the current discussion of effects of physical activity on the immune system of breast cancer patients. Highlighted are effects of physical activity on the immune system. Seven original articles and 14 reviews included in this review. Two original and the review articles includes other tumor entities besides breast cancer.Evaluated methods such as dose-response relationships for exercise in oncology, hardly exist. Increased immunological anti-cancer activity due to physical activity is probably mediated via an increase in number and cytotoxicity of monocytes and natural killer cells and cytokines.

  2. Accuracy of Self-Reported Breast Cancer Information among Women from the Ontario Site of the Breast Cancer Family Registry

    International Nuclear Information System (INIS)

    Barisic, A.; Glendon, G.; Andrulis, I. L.; Knight, J. A.; Barisic, A.; Knight, J. A.; Glendon, G.; Weerasooriya, N.; Andrulis, I. L.

    2012-01-01

    Obtaining complete medical record information can be challenging and expensive in breast cancer studies. The current literature is limited with respect to the accuracy of self-report and factors that may influence this. We assessed the agreement between self-reported and medical record breast cancer information among women from the Ontario site of the Breast Cancer Family Registry. Women aged 20-69 years diagnosed with incident breast cancer 1996-1998 were identified from the Ontario Cancer Registry, sampled on age and family history. We calculated kappa statistics, proportion correct, sensitivity, specificity, and positive and negative predictive values and conducted unconditional logistic regression to examine whether characteristics of the women influenced agreement. The proportions of women who correctly reported having received a broad category of therapy (hormone therapy, chemotherapy, radiation, or surgery) as well as sensitivity and specificity were above 90%, and the kappa statistics were above 0.80. The specific type of hormonal or chemotherapy was reported with low-to-moderate agreement. Aside from recurrence, no factors were consistently associated with agreement. Thus, most women were able to accurately report broad categories of treatment but not necessarily specific treatment types. The finding of this study can aid researchers in the use and design of self-administered treatment questionnaires

  3. THE CLINICAL SIGNIFICANCE OF 99mTc-MIBI BREAST IMAGING IN THE DIAGNOSIS OF EARLY BREAST CANCER

    Institute of Scientific and Technical Information of China (English)

    任长才; 金少津; 邹强; 朱汇庆; 王红鹰; 梁春立

    2001-01-01

    Objective: To find an effective, sensitive, specific and noninvasive diagnostic method of breast cancer. Methods: 109 masses of 102 patients with breast lesions smaller than 2 cm in diameter were divided into three groups to undergo 99mTc-MIBI imaging and compared with the results of pathology examination. 20 cases without breast lesions were selected as control. Abnormal condensation of 99mTc-MIBI in the breast reaching 10% higher than that in the counterpart of the healthy breast was regarded as positive. Results: Of 32 breast cancers, positive imaging appeared in 25. Negative imaging were found in 31 of 38 benign breast lesions. Of 39 occult breast lesions, positive imaging appeared in 6 and 3 of them were breast cancer, 2 of 3 patients with slightly increased 99mTc-MIBI imaging threshold were breast cancer also. No positive imaging was found in the control group. The diagnostic accuracy, sensitivity, specificity, positive predictive value, negative predictive value of 99mTc-MIBI was 88.4%, 89.2%, 88.0%, 75.0% and 95.3%, respectively. Conclusion: 99mTc-MIBI imaging had higher sensitivity and accuracy in the diagnosis of breast cancer and differentiation between benign and malignant breast lesions. It could provide useful information for the diagnosis of clinically suspected breast cancer.

  4. Preventative therapies for healthy women at high risk of breast cancer

    International Nuclear Information System (INIS)

    Sestak, Ivana

    2014-01-01

    Tamoxifen has been shown to reduce the risk of developing estrogen receptor (ER)-positive breast cancer by at least 50%, in both pre- and postmenopausal women. The current challenge is to find new agents with fewer side effects and to find agents that are specifically suitable for premenopausal women with ER-negative breast cancer. Other selective estrogen receptor modulators (SERMs), such as raloxifene, arzoxifene, and lasofoxifene, have been shown to reduce the incidence of breast cancer by 50%–80%. SERMs are interesting agents for the prevention of breast cancer, but longer follow-up is needed for some of them for a complete risk–benefit profile of these drugs. Aromatase inhibitors have emerged as new drugs in the prevention setting for postmenopausal women. In the Mammary Prevention 3 (MAP3) trial, a 65% reduction in invasive breast cancer with exemestane was observed, and the Breast Cancer Intervention Study-II trial, which compared anastrozole with placebo, reported a 60% reduction in those cancers. Although SERMs and aromatase inhibitors have been proven to be excellent agents in the preventive setting specifically for postmenopausal women and ER-positive breast cancer, newer agents have to be found specifically for ER-negative breast cancers, which mostly occur in premenopausal women

  5. Analysis of 10-year cause-specific mortality of patients with breast cancer treated in New South Wales in 1995

    International Nuclear Information System (INIS)

    Wang, Wei; Stuart, Kirsty; Boyages, John; O'Connell, Dianne

    2011-01-01

    The objective of this study is to assess cause-specific mortality for patients with breast cancer and to determine if excess cardiac death was associated with radiation therapy (RT). We obtained 10-year cause-specific mortality information from the New South Wales (NSW) Central Cancer Registry and National Death Index on 1242 patients with unilateral stage I–III invasive breast cancer in NSW, Australia, diagnosed over a 6-month period in 1995. We compared actuarial cause-specific mortality (breast cancer, cardiac, other cancers and other causes) for patients who received left-sided, right-sided or no RT. Mortality due to breast cancer or due to other cancers was not significantly different (P = 0.30 and P = 0.11) between the three subgroups. Mortality due to cardiac and other causes was higher in patients who did not have radiotherapy (P = 0.001 and P < 0.001). A total of 52 cardiac deaths in 1242 patients (4.2%) occurred – six of 274 patients (2.2%) in the left-sided radiotherapy group, four of 245 patients (1.6%) in the right-sided radiotherapy group (P = 0.63) and 42 of 723 patients (5.8%) in the no radiotherapy group. Most cardiac deaths (46 of 52 cases) occurred in patients aged 70 years or older at the time of diagnosis. There were no differences in cardiac mortality between the three treatment groups for those aged 70 years or older (P = 0.22, log-rank test), suggesting that the higher overall cardiac mortality rate in the no-RT group is due to a higher percentage of patients aged 70 years or older. Of the 10 patients who died from cardiac causes and who had received RT, none had received chemotherapy or irradiation to the internal mammary chain. There is no excess cardiac mortality due to RT within the first decade in a population series of patients with breast cancer treated with modern radiotherapy.

  6. Pristimerin overcomes adriamycin resistance in breast cancer cells through suppressing Akt signaling

    Science.gov (United States)

    XIE, GUI'E; YU, XINPEI; LIANG, HUICHAO; CHEN, JINGSONG; TANG, XUEWEI; WU, SHAOQING; LIAO, CAN

    2016-01-01

    Breast cancer remains a major public health problem worldwide. Chemotherapy serves an important role in the treatment of breast cancer. However, resistance to chemotherapeutic agents, in particular, multi-drug resistance (MDR), is a major cause of treatment failure in cancer. Agents that can either enhance the effects of chemotherapeutics or overcome chemoresistance are urgently needed for the treatment of breast cancer. Pristimerin, a quinonemethide triterpenoid compound isolated from Celastraceae and Hippocrateaceae, has been shown to possess antitumor, anti-inflammatory, antioxidant and insecticidal properties. The aim of the present study was to investigate whether pristimerin can override chemoresistance in MCF-7/adriamycin (ADR)-resistant human breast cancer cells. The results demonstrated that pristimerin indeed displayed potent cytocidal effect on multidrug-resistant MCF-7/ADR breast cancer cells, and that these effects occurred through the suppression of Akt signaling, which in turn led to the downregulation of antiapoptotic effectors and increased apoptosis. These findings indicate that use of pristimerin may represent a potentially promising approach for the treatment of ADR-resistant breast cancer. PMID:27123073

  7. Cancer Chemotherapy Specific to Acidic Nests.

    Science.gov (United States)

    Kobayashi, Hiroshi

    2017-04-20

    The realization of cancer therapeutics specific to cancer cells with less of an effect on normal tissues is our goal. Many trials have been carried out for this purpose, but this goal is still far from being realized. It was found more than 80 years ago that solid cancer nests are acidified, but in vitro studies under acidic conditions have not been extensively studied. Recently, in vitro experiments under acidic conditions were started and anti-cancer drugs specific to acidic areas have been identified. Many genes have been reported to be expressed at a high level under acidic conditions, and such genes may be potent targets for anti-cancer drugs specific to acidic nests. In this review article, recent in vitro, in vivo, and clinical achievements in anti-cancer drugs with marked efficacy under acidic conditions are summarized, and the clinical use of anti-cancer drugs specific to acidic nests is discussed.

  8. Inheritance of proliferative breast disease in breast cancer kindreds

    International Nuclear Information System (INIS)

    Skolnick, M.H.; Cannon-Albright, L.A.; Goldgar, D.E.; Ward, J.H.; Marshall, C.J.; Schumann, G.B.; Hogle, H.; McWhorter, W.P.; Wright, E.C.; Tran, T.D.; Bishop, D.T.; Kushner, J.P.; Eyre, H.J.

    1990-01-01

    Previous studies have emphasized that genetic susceptibility to breast cancer is rare and is expressed primarily as premenopausal breast cancer, bilateral breast cancer, or both. Proliferative breast disease (PBD) is a significant risk factor for the development of breast cancer and appears to be a precursor lesion. PBD and breast cancer were studied in 103 women from 20 kindreds that were selected for the presence of two first degree relatives with breast cancer and in 31 control women. Physical examination, screening mammography, and four-quadrant fine-needle breast aspirates were performed. Cytologic analysis of breast aspirates revealed PBD in 35% of clinically normal female first degree relatives of breast cancer cases and in 13% of controls. Genetic analysis suggests that genetic susceptibility causes both PBD and breast cancer in these kindreds. This study supports the hypothesis that this susceptibility is responsible for a considerable portion of breast cancer, including unilateral and postmenopausal breast cancer

  9. Newly Synthesized Doxorubicin Complexes with Selected Metals—Synthesis, Structure and Anti-Breast Cancer Activity

    Directory of Open Access Journals (Sweden)

    Agata Jabłońska-Trypuć

    2017-07-01

    Full Text Available Doxorubicin (DOX is very effective chemotherapeutic agent, however it has several major drawbacks. Therefore the motivation for developing novel drug complexes as anticancer agents with different mechanism of action has arisen. The aim of the present study was to evaluate the influence of newly synthesized DOX complexes with selected metals (Mg, Mn, Co, Ni, Fe, Cu, Zn on apoptosis, cell cycle, viability, proliferation and cytotoxicity in the breast cancer cell line MCF-7. Complexation of DOX with metals has likewise been the subject of our research. The current work showed that the tested bivalent metals at a given pH condition formed metal:DOX complexes in a ratio of 2:1, while iron complexes with DOX in a ratio of 3:1. The studies also showed that selected metal-DOX complexes (Mg-DOX, Mn-DOX, Ni-DOX at 0.5 µM concentration significantly decreased cell viability and proliferation, however they increased caspase 7 activity. Results also indicated that studied metal-DOX complexes showed high cytotoxicity in MCF-7 cells. Therefore they were chosen for cell cycle check-points and apoptosis/necrosis analysis studied by flow cytometry. Obtained results suggest that doxorubicin complexed by specified metals can be considered as a potential anti-breast cancer agent, which is characterized by a higher efficacy than a parent drug.

  10. Radiogenic breast cancer risk and mammography

    International Nuclear Information System (INIS)

    Jayaprakash, Shobha; Nair, C.P.R.; Rao, B.S.; Sawant, S.G.

    2001-01-01

    There is a general concern that the risks from mammography screening in inducting radiogenic breast cancer may outweigh the possible benefits to be derived from it. A review of epidemiological, case-control and cohort studies of radiogenic breast cancer, age-specific incidence and dose and dose-rate relationship reveals that such a fear is unfounded. The dose to the breast tissues in a quality assured mammography screening programme falls far below the levels that were observed to produce increased relative risk. The age-specific incidence rates also indicate that the need for mammography is for the women of age at which the relative risk is minimum

  11. Leptin: A proliferative factor for breast cancer?

    International Nuclear Information System (INIS)

    Caldefie-Chezet, F.; Damez, M.; Latour, M. de; Konska, G.; Mishellani, F.; Fusillier, C.; Guerry, M.; Penault-Llorca, F.; Guillot, J.; Vasson, M.-P.

    2005-01-01

    Mammary adipose tissue is an important source of paracrine mitogens and anti-mitogens, including insulin-like growth factor, transforming growth factors, and cytokines (especially, TNFα and IL-1β). Nevertheless, it is also an important source of the adipocytokine, leptin. Recently, leptin was reported to stimulate the proliferation of various cell types (pancreatic β cells, prostate, colorectal, lung, etc.) as a new growth factor. It was also shown to stimulate the proliferation of breast cancer cell lines. In this study, we conducted an immunohistochemical analysis of leptin expression in normal tissue and benign and malignant ductal breast cell, representing the different states of the invasion process. We determined for the first time that leptin is expressed both by ductal breast tumors and by benign lesions as atypical hyperplasia. This suggests that leptin may be taken up or synthesized by all modified ductal breast cells, and may prove a proliferative factor. Moreover, leptin is unexpressed by normal tissue in the healthy breast but is exhibited by the normal tissue in near vicinity of the malignant ductal breast lesions. We also postulated that leptin may be a prognostic or diagnostic factor for ductal breast cancer. These putative hypotheses require further study

  12. Leptin’s Pro-Angiogenic Signature in Breast Cancer

    International Nuclear Information System (INIS)

    Gonzalez-Perez, Ruben Rene; Lanier, Viola; Newman, Gale

    2013-01-01

    Obesity is linked to increased incidence of breast cancer. The precise causes and mechanisms of these morbid relationships are unknown. Contradictory data on leptin angiogenic actions have been published. However, accumulating evidence would suggest that leptin’s pro-angiogenic effects in cancer play an essential role in the disease. Leptin, the main adipokine secreted by adipose tissue, is also abnormally expressed together with its receptor (OB-R) by breast cancer cells. Leptin induces proliferation and angiogenic differentiation of endothelial cells upregulates VEGF/VEGFR2 and transactivates VEGFR2 independent of VEGF. Leptin induces two angiogenic factors: IL-1 and Notch that can increase VEGF expression. Additionally, leptin induces the secretion and synthesis of proteases and adhesion molecules needed for the development of angiogenesis. Leptin’s paracrine actions can further affect stromal cells and tumor associated macrophages, which express OB-R and secrete VEGF and IL-1, respectively. A complex crosstalk between leptin, Notch and IL-1 (NILCO) that induces VEGF/VEGFR2 is found in breast cancer. Leptin actions in tumor angiogenesis could amplify, be redundant and/or compensatory to VEGF signaling. Current failure of breast cancer anti-angiogenic therapies emphasizes the necessity of targeting the contribution of other pro-angiogenic factors in breast cancer. Leptin’s impact on tumor angiogenesis could be a novel target for breast cancer, especially in obese patients. However, more research is needed to establish the importance of leptin in tumor angiogenesis. This review is focused on updated information on how leptin could contribute to tumor angiogenesis

  13. Downregulation of TXNIP leads to high proliferative activity and estrogen-dependent cell growth in breast cancer.

    Science.gov (United States)

    Park, Jun Won; Lee, Su Hyung; Woo, Gye-Hyung; Kwon, Hyo-Jung; Kim, Dae-Yong

    2018-04-06

    TXNIP is a potent tumor suppressor with reduced expression in various types of human cancer. The prognostic and predictive power of TXNIP has been recognized in human breast cancer. The aim of this study is to investigate the clinical relevance and functional roles of TXNIP downregulation in breast cancer. We examined TXNIP expression at the protein level in tissue microarray (TMA)-based human breast cancers and its correlation with clinical parameters and molecular markers on immunohistochemistry (IHC). Compared with normal tissues, TXNIP expression was significantly decreased in human breast cancer tissues and animal mammary tumors, along with tumor progression. TXNIP was restored immediately after histone deacetylase inhibitor treatment in breast cancer cells, implying transcriptional regulation of TXNIP by histone modification. Decreased TXNIP protein levels were more common in tumors showing high proliferative activity, such as high Ki-67 labeling indexes and low p27 expression. TXNIP knockdown led to increased in vitro and in vivo breast cancer cell growth accompanied by p27 reduction and GLUT1 induction. Interestingly, estrogen receptor (ER)-positive breast cancer samples showed higher TXNIP expression compared to ER-negative samples. TXNIP expression decreased when ER signaling was activated by estradiol, while its expression increased under ER blockage by anti-estrogen fulvestrant. In addition, TXNIP knockdown in breast cancer cells caused significant reduction in the cell-growth inhibitory effect of anti-estrogen fulvestrant. In conclusion, our data demonstrated that TXNIP functions to suppress high proliferative activity and estrogen-dependent cell growth in breast cancer. Copyright © 2018 Elsevier Inc. All rights reserved.

  14. Circulating microRNAs in breast cancer

    DEFF Research Database (Denmark)

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

    2017-01-01

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

  15. Pharmacodynamics, pharmacokinetics and clinical efficacy of neratinib in HER2-positive breast cancer and breast cancer with HER2 mutations.

    Science.gov (United States)

    Kourie, Hampig Raphael; Chaix, Marie; Gombos, Andrea; Aftimos, Phillippe; Awada, Ahmad

    2016-08-01

    Despite the availability of several potent HER2-directed targeted agents, primary and acquired resistance continues to influence patient outcomes in HER2-positive breast cancer. Neratinib is an irreversible pan-HER tyrosine kinase inhibitor in late-phase clinical development. This review article focuses on neratinib in the treatment of HER2-positive breast cancer - early and metastatic stage - and HER2-mutant breast cancer, with particular emphasis on the pharmacokinetics and pharmacodynamics of the drug. The phase III ExteNET trial shows that neratinib improves 2-year invasive disease-free survival after trastuzumab-based adjuvant therapy in early-stage HER2-positive breast cancer, and in particular HER2+/HR+ tumors. Survival data are awaited. The investigational role of neratinib in high-risk patients or conversely in de-escalation dual regimens with other anti-HER2 therapies and without chemotherapy are of interest. Phase II trials show that neratinib has efficacy, either as monotherapy or in combination with other chemotherapeutic or endocrine agents, in patients with HER2-positive metastatic breast cancer and in tumors harboring HER2 mutations. The role of neratinib in therapeutic algorithms of HER2-positive patients, as well as delaying CNS events, awaits the results of ongoing trials such as NALA. Diarrhea, the main toxicity of neratinib, can be effectively managed with early loperamide prophylaxis.

  16. Male Breast Cancer

    Science.gov (United States)

    ... types of breast cancer that can occur in men include Paget's disease of the nipple and inflammatory breast cancer. Inherited genes that increase breast cancer risk Some men inherit abnormal (mutated) genes from their parents that ...

  17. Inflammatory Breast Cancer

    Science.gov (United States)

    ... Common Cancer Types Recurrent Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer ... white women. Inflammatory breast tumors are frequently hormone receptor negative, which means they cannot be treated with ...

  18. Molecular characterization of irinotecan (SN-38) resistant human breast cancer cell lines

    DEFF Research Database (Denmark)

    Jandu, Haatisha; Aluzaite, Kristina; Fogh, Louise

    2016-01-01

    Background: Studies in taxane and/or anthracycline refractory metastatic breast cancer (mBC) patients have shown approximately 30 % response rates to irinotecan. Hence, a significant number of patients will experience irinotecan-induced side effects without obtaining any benefit. The aim of this ......Background: Studies in taxane and/or anthracycline refractory metastatic breast cancer (mBC) patients have shown approximately 30 % response rates to irinotecan. Hence, a significant number of patients will experience irinotecan-induced side effects without obtaining any benefit. The aim...... or an initial high dose of SN-38 (the active metabolite of irinotecan), respectively. The resistant cell lines were analyzed for cross-resistance to other anti-cancer drugs, global gene expression, growth rates, TOP1 and TOP2A gene copy numbers and protein expression, and inhibition of the breast cancer...... of the BCRP in breast cancer patients scheduled for irinotecan treatment. Moreover, LMP400 should be tested in a clinical setting in breast cancer patients with resistance to irinotecan....

  19. Mediterranean dietary pattern and risk of breast cancer.

    Directory of Open Access Journals (Sweden)

    Elisabeth Couto

    Full Text Available BACKGROUND: A Mediterranean diet has a recognized beneficial effect on health and longevity, with a protective influence on several cancers. However, its association with breast cancer risk remains unclear. OBJECTIVE: We aimed to investigate whether adherence to a Mediterranean dietary pattern influences breast cancer risk. DESIGN: The Swedish Women's Lifestyle and Health cohort study includes 49,258 women aged 30 to 49 years at recruitment in 1991-1992. Consumption of foods and beverages was measured at enrollment using a food frequency questionnaire. A Mediterranean diet score was constructed based on the consumption of alcohol, vegetables, fruits, legumes, cereals, fish, the ratio of unsaturated to saturated fat, and dairy and meat products. Relative risks (RR for breast cancer and specific tumor characteristics (invasiveness, histological type, estrogen/progesterone receptor status, malignancy grade and stage associated with this score were estimated using Cox regression controlling for potential confounders. RESULTS: 1,278 incident breast cancers were diagnosed. Adherence to a Mediterranean dietary pattern was not statistically significantly associated with reduced risk of breast cancer overall, or with specific breast tumor characteristics. A RR (95% confidence interval for breast cancer associated with a two-point increment in the Mediterranean diet score was 1.08 (1.00-1.15 in all women, and 1.10 (1.01-1.21 and 1.02 (0.91-1.15 in premenopausal and postmenopausal women, respectively. When alcohol was excluded from the Mediterranean diet score, results became not statistically significant. CONCLUSIONS: Adherence to a Mediterranean dietary pattern did not decrease breast cancer risk in this cohort of relatively young women.

  20. Estimating the Risks of Breast Cancer Radiotherapy

    DEFF Research Database (Denmark)

    Taylor, Carolyn; Correa, Candace; Duane, Frances K

    2017-01-01

    Purpose Radiotherapy reduces the absolute risk of breast cancer mortality by a few percentage points in suitable women but can cause a second cancer or heart disease decades later. We estimated the absolute long-term risks of modern breast cancer radiotherapy. Methods First, a systematic literature...... review was performed of lung and heart doses in breast cancer regimens published during 2010 to 2015. Second, individual patient data meta-analyses of 40,781 women randomly assigned to breast cancer radiotherapy versus no radiotherapy in 75 trials yielded rate ratios (RRs) for second primary cancers...... and cause-specific mortality and excess RRs (ERRs) per Gy for incident lung cancer and cardiac mortality. Smoking status was unavailable. Third, the lung or heart ERRs per Gy in the trials and the 2010 to 2015 doses were combined and applied to current smoker and nonsmoker lung cancer and cardiac mortality...

  1. Birth weight, breast cancer and the potential mediating hormonal environment.

    Directory of Open Access Journals (Sweden)

    Radek Bukowski

    Full Text Available Previous studies have shown that woman's risk of breast cancer in later life is associated with her infants birth weights. The objective of this study was to determine if this association is independent of breast cancer risk factors, mother's own birth weight and to evaluate association between infants birth weight and hormonal environment during pregnancy. Independent association would have implications for understanding the mechanism, but also for prediction and prevention of breast cancer.Risk of breast cancer in relation to a first infant's birth weight, mother's own birth weight and breast cancer risk factors were evaluated in a prospective cohort of 410 women in the Framingham Study. Serum concentrations of estriol (E3, anti-estrogen alpha-fetoprotein (AFP, and pregnancy-associated plasma protein-A (PAPP-A were measured in 23,824 pregnant women from a separate prospective cohort, the FASTER trial. During follow-up (median, 14 years 31 women (7.6% were diagnosed with breast cancer. Women with large birth weight infants (in the top quintile had a higher breast cancer risk compared to other women (hazard ratio (HR, 2.5; 95% confidence interval (CI, 1.2-5.2; P = 0.012. The finding was not affected by adjustment for birth weight of the mother and traditional breast cancer risk factors (adjusted HR, 2.5; 95% CI, 1.2-5.6; P = 0.021. An infant's birth weight had a strong positive relationship with the mother's serum E3/AFP ratio and PAPP-A concentration during pregnancy. Adjustment for breast cancer risk factors did not have a material effect on these relationships.Giving birth to an infant with high birth weight was associated with increased breast cancer risk in later life, independently of mother's own birth weight and breast cancer risk factors and was also associated with a hormonal environment during pregnancy favoring future breast cancer development and progression.

  2. Identification of novel genetic markers of breast cancer survival

    DEFF Research Database (Denmark)

    Guo, Qi; Schmidt, Marjanka K; Kraft, Peter

    2015-01-01

    BACKGROUND: Survival after a diagnosis of breast cancer varies considerably between patients, and some of this variation may be because of germline genetic variation. We aimed to identify genetic markers associated with breast cancer-specific survival. METHODS: We conducted a large meta-analysis ......BACKGROUND: Survival after a diagnosis of breast cancer varies considerably between patients, and some of this variation may be because of germline genetic variation. We aimed to identify genetic markers associated with breast cancer-specific survival. METHODS: We conducted a large meta......-analysis of studies in populations of European ancestry, including 37954 patients with 2900 deaths from breast cancer. Each study had been genotyped for between 200000 and 900000 single nucleotide polymorphisms (SNPs) across the genome; genotypes for nine million common variants were imputed using a common reference...... panel from the 1000 Genomes Project. We also carried out subtype-specific analyses based on 6881 estrogen receptor (ER)-negative patients (920 events) and 23059 ER-positive patients (1333 events). All statistical tests were two-sided. RESULTS: We identified one new locus (rs2059614 at 11q24...

  3. Remarkable change in age-specific breast cancer incidence in the Swiss canton of Geneva and its possible relation with the use of hormone replacement therapy

    International Nuclear Information System (INIS)

    Bouchardy, Christine; Morabia, Alfredo; Verkooijen, Helena M; Fioretta, Gérald; Wespi, Yves; Schäfer, Peter

    2006-01-01

    This article aims to explain the reasons for the remarkable change in age of breast cancer occurrence in the Swiss canton of Geneva. We used population-based data from the Geneva cancer registry, which collects information on method of detection, stage and tumour characteristics since 1975. For patients diagnosed between 1997–2003, we obtained additional information on use of hormone replacement therapy from a large prospective study on breast cancer. Using generalized log linear regression analysis, we compared age-specific incidence rates with respect to period, stage, oestrogen receptor status, method of detection and use of hormone replacement therapy. In the periods 1975–1979 and 1985–1989, breast cancer risk increased with age, showing the highest incidence rates among women aged ≥ 85 years. From 1997, the age-specific incidence curve changed completely (p < 0.0001), showing an incidence peak at 60–64 years and a reduced incidence among elderly women. This incidence peak concerned mainly early stage and oestrogen positive cancers and was exclusively observed among women who ever used hormone replacement therapy, regardless whether the tumour was screen-detected or not. The increasing prevalence of hormone replacement therapy use during the 1990s could explain the important change in age-specific breast cancer incidence, not only by increasing breast cancer risk, but also by revealing breast cancer at an earlier age

  4. Annotating breast cancer microarray samples using ontologies

    Science.gov (United States)

    Liu, Hongfang; Li, Xin; Yoon, Victoria; Clarke, Robert

    2008-01-01

    As the most common cancer among women, breast cancer results from the accumulation of mutations in essential genes. Recent advance in high-throughput gene expression microarray technology has inspired researchers to use the technology to assist breast cancer diagnosis, prognosis, and treatment prediction. However, the high dimensionality of microarray experiments and public access of data from many experiments have caused inconsistencies which initiated the development of controlled terminologies and ontologies for annotating microarray experiments, such as the standard microarray Gene Expression Data (MGED) ontology (MO). In this paper, we developed BCM-CO, an ontology tailored specifically for indexing clinical annotations of breast cancer microarray samples from the NCI Thesaurus. Our research showed that the coverage of NCI Thesaurus is very limited with respect to i) terms used by researchers to describe breast cancer histology (covering 22 out of 48 histology terms); ii) breast cancer cell lines (covering one out of 12 cell lines); and iii) classes corresponding to the breast cancer grading and staging. By incorporating a wider range of those terms into BCM-CO, we were able to indexed breast cancer microarray samples from GEO using BCM-CO and MGED ontology and developed a prototype system with web interface that allows the retrieval of microarray data based on the ontology annotations. PMID:18999108

  5. Male Breast Cancer

    Science.gov (United States)

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

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

    NARCIS (Netherlands)

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

    2002-01-01

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

  7. Local breast cancer spatial patterning: a tool for community health resource allocation to address local disparities in breast cancer mortality.

    Directory of Open Access Journals (Sweden)

    Dana M Brantley-Sieders

    Full Text Available Despite available demographic data on the factors that contribute to breast cancer mortality in large population datasets, local patterns are often overlooked. Such local information could provide a valuable metric by which regional community health resources can be allocated to reduce breast cancer mortality. We used national and statewide datasets to assess geographical distribution of breast cancer mortality rates and known risk factors influencing breast cancer mortality in middle Tennessee. Each county in middle Tennessee, and each ZIP code within metropolitan Davidson County, was scored for risk factor prevalence and assigned quartile scores that were used as a metric to identify geographic areas of need. While breast cancer mortality often correlated with age and incidence, geographic areas were identified in which breast cancer mortality rates did not correlate with age and incidence, but correlated with additional risk factors, such as mammography screening and socioeconomic status. Geographical variability in specific risk factors was evident, demonstrating the utility of this approach to identify local areas of risk. This method revealed local patterns in breast cancer mortality that might otherwise be overlooked in a more broadly based analysis. Our data suggest that understanding the geographic distribution of breast cancer mortality, and the distribution of risk factors that contribute to breast cancer mortality, will not only identify communities with the greatest need of support, but will identify the types of resources that would provide the most benefit to reduce breast cancer mortality in the community.

  8. Anti-Cancer Properties of Diethylether Extract of Wood from Sukun ...

    African Journals Online (AJOL)

    Purpose: To evaluate the anti-cancer properties of the diethylether extract of Sukun (Artocarpus altilis) wood. Methods: The extract was tested in human T47D breast cancer cells and examined for its effect on cell viability, nuclear morphology and sub-G1 formation. Cell viability was determined by microculture tetrazolium ...

  9. Antibacterial and anti-breast cancer cell line activities of ...

    African Journals Online (AJOL)

    Purpose: To evaluate the activity of extracts of Sanghuangporus sp.1 fungus against pathogenic bacteria and a breast cancer cell line. Methods: The wild fruiting body and mycelium of Sanghuangporus sp.1 were extracted with water and ethanol by ultrasonication extraction. The activity of the extracts against pathogenic ...

  10. Mitochondria-targeted vitamin E analogs inhibit breast cancer cell energy metabolism and promote cell death

    International Nuclear Information System (INIS)

    Cheng, Gang; Zielonka, Jacek; McAllister, Donna M; Mackinnon, A Craig Jr; Joseph, Joy; Dwinell, Michael B; Kalyanaraman, Balaraman

    2013-01-01

    Recent research has revealed that targeting mitochondrial bioenergetic metabolism is a promising chemotherapeutic strategy. Key to successful implementation of this chemotherapeutic strategy is the use of new and improved mitochondria-targeted cationic agents that selectively inhibit energy metabolism in breast cancer cells, while exerting little or no long-term cytotoxic effect in normal cells. In this study, we investigated the cytotoxicity and alterations in bioenergetic metabolism induced by mitochondria-targeted vitamin E analog (Mito-chromanol, Mito-ChM) and its acetylated ester analog (Mito-ChMAc). Assays of cell death, colony formation, mitochondrial bioenergetic function, intracellular ATP levels, intracellular and tissue concentrations of tested compounds, and in vivo tumor growth were performed. Both Mito-ChM and Mito-ChMAc selectively depleted intracellular ATP and caused prolonged inhibition of ATP-linked oxygen consumption rate in breast cancer cells, but not in non-cancerous cells. These effects were significantly augmented by inhibition of glycolysis. Mito-ChM and Mito-ChMAc exhibited anti-proliferative effects and cytotoxicity in several breast cancer cells with different genetic background. Furthermore, Mito-ChM selectively accumulated in tumor tissue and inhibited tumor growth in a xenograft model of human breast cancer. We conclude that mitochondria-targeted small molecular weight chromanols exhibit selective anti-proliferative effects and cytotoxicity in multiple breast cancer cells, and that esterification of the hydroxyl group in mito-chromanols is not a critical requirement for its anti-proliferative and cytotoxic effect

  11. BCL-2 family protein, BAD is down-regulated in breast cancer and inhibits cell invasion

    Energy Technology Data Exchange (ETDEWEB)

    Cekanova, Maria, E-mail: mcekanov@utk.edu [Department of Small Animal Clinical Sciences, College of Veterinary Medicine, The University of Tennessee, Knoxville, TN (United States); Fernando, Romaine I. [Department of Obstetrics and Gynecology, Graduate School of Medicine, Medical Center, The University of Tennessee, Knoxville, TN (United States); Siriwardhana, Nalin [Department of Animal Science, The University of Tennessee, Knoxville, TN (United States); Sukhthankar, Mugdha [Department of Biomedical and Diagnostics Sciences, College of Veterinary Medicine, The University of Tennessee, Knoxville, TN (United States); Parra, Columba de la [Department of Biochemistry, School of Medicine, University of Puerto Rico, Medical Sciences Campus, San Juan, PR (United States); Woraratphoka, Jirayus [Department of Obstetrics and Gynecology, Graduate School of Medicine, Medical Center, The University of Tennessee, Knoxville, TN (United States); Malone, Christine [Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, NC (United States); Ström, Anders [Center for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston, Houston, TX (United States); Baek, Seung J. [Department of Biomedical and Diagnostics Sciences, College of Veterinary Medicine, The University of Tennessee, Knoxville, TN (United States); Wade, Paul A. [Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, NC (United States); Saxton, Arnold M. [Department of Animal Science, The University of Tennessee, Knoxville, TN (United States); Donnell, Robert M. [Department of Biomedical and Diagnostics Sciences, College of Veterinary Medicine, The University of Tennessee, Knoxville, TN (United States); Pestell, Richard G. [Department of Cancer Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA (United States); and others

    2015-02-01

    We have previously demonstrated that the anti-apoptotic protein BAD is expressed in normal human breast tissue and shown that BAD inhibits expression of cyclin D1 to delay cell-cycle progression in breast cancer cells. Herein, expression of proteins in breast tissues was studied by immunohistochemistry and results were analyzed statistically to obtain semi-quantitative data. Biochemical and functional changes in BAD-overexpressing MCF7 breast cancer cells were evaluated using PCR, reporter assays, western blotting, ELISA and extracellular matrix invasion assays. Compared to normal tissues, Grade II breast cancers expressed low total/phosphorylated forms of BAD in both cytoplasmic and nuclear compartments. BAD overexpression decreased the expression of β-catenin, Sp1, and phosphorylation of STATs. BAD inhibited Ras/MEK/ERK and JNK signaling pathways, without affecting the p38 signaling pathway. Expression of the metastasis-related proteins, MMP10, VEGF, SNAIL, CXCR4, E-cadherin and TlMP2 was regulated by BAD with concomitant inhibition of extracellular matrix invasion. Inhibition of BAD by siRNA increased invasion and Akt/p-Akt levels. Clinical data and the results herein suggest that in addition to the effect on apoptosis, BAD conveys anti-metastatic effects and is a valuable prognostic marker in breast cancer. - Highlights: • BAD and p-BAD expressions are decreased in breast cancer compared with normal breast tissue. • BAD impedes breast cancer invasion and migration. • BAD inhibits the EMT and transcription factors that promote cancer cell migration. • Invasion and migration functions of BAD are distinct from the BAD's role in apoptosis.

  12. BCL-2 family protein, BAD is down-regulated in breast cancer and inhibits cell invasion

    International Nuclear Information System (INIS)

    Cekanova, Maria; Fernando, Romaine I.; Siriwardhana, Nalin; Sukhthankar, Mugdha; Parra, Columba de la; Woraratphoka, Jirayus; Malone, Christine; Ström, Anders; Baek, Seung J.; Wade, Paul A.; Saxton, Arnold M.; Donnell, Robert M.; Pestell, Richard G.

    2015-01-01

    We have previously demonstrated that the anti-apoptotic protein BAD is expressed in normal human breast tissue and shown that BAD inhibits expression of cyclin D1 to delay cell-cycle progression in breast cancer cells. Herein, expression of proteins in breast tissues was studied by immunohistochemistry and results were analyzed statistically to obtain semi-quantitative data. Biochemical and functional changes in BAD-overexpressing MCF7 breast cancer cells were evaluated using PCR, reporter assays, western blotting, ELISA and extracellular matrix invasion assays. Compared to normal tissues, Grade II breast cancers expressed low total/phosphorylated forms of BAD in both cytoplasmic and nuclear compartments. BAD overexpression decreased the expression of β-catenin, Sp1, and phosphorylation of STATs. BAD inhibited Ras/MEK/ERK and JNK signaling pathways, without affecting the p38 signaling pathway. Expression of the metastasis-related proteins, MMP10, VEGF, SNAIL, CXCR4, E-cadherin and TlMP2 was regulated by BAD with concomitant inhibition of extracellular matrix invasion. Inhibition of BAD by siRNA increased invasion and Akt/p-Akt levels. Clinical data and the results herein suggest that in addition to the effect on apoptosis, BAD conveys anti-metastatic effects and is a valuable prognostic marker in breast cancer. - Highlights: • BAD and p-BAD expressions are decreased in breast cancer compared with normal breast tissue. • BAD impedes breast cancer invasion and migration. • BAD inhibits the EMT and transcription factors that promote cancer cell migration. • Invasion and migration functions of BAD are distinct from the BAD's role in apoptosis

  13. Associations of parity-related reproductive histories with ER± and HER2± receptor-specific breast cancer aetiology

    DEFF Research Database (Denmark)

    Anderson, William F; Pfeiffer, Ruth M; Wohlfahrt, Jan

    2017-01-01

    ± expression. Methods: We linked a cancer registry covering nearly 95% of the primary breast cancer diagnoses in Denmark with a research parity database to assess associations for parity, number of live births and age at first live birth (AFLB) with receptor-specific risk. Relative risks (RRs) for associations...

  14. Korean women: breast cancer knowledge, attitudes and behaviors

    Directory of Open Access Journals (Sweden)

    Ryujin Lisa T

    2001-08-01

    Full Text Available Abstract Introduction Clustered within the nomenclature of Asian American are numerous subgroups, each with their own ethnic heritage, cultural, and linguistic characteristics. An understanding of the prevailing health knowledge, attitudes, and screening behaviors of these subgroups is essential for creating population-specific health promotion programs. Methods Korean American women (123 completed baseline surveys of breast cancer knowledge, attitudes, and screening behaviors as part of an Asian grocery store-based breast cancer education program evaluation. Follow-up telephone surveys, initiated two weeks later, were completed by 93 women. Results Low adherence to the American Cancer Society's breast cancer screening guidelines and insufficient breast cancer knowledge were reported. Participants' receptiveness to the grocery store-based breast cancer education program underscores the importance of finding ways to reach Korean women with breast cancer early detection information and repeated cues for screening. The data also suggest that the Asian grocery store-based cancer education program being tested may have been effective in motivating a proportion of the women to schedule a breast cancer screening between the baseline and follow-up surveys. Conclusion The program offers a viable strategy to reach Korean women that addresses the language, cultural, transportation, and time barriers they face in accessing breast cancer early detection information.

  15. Anti-protozoal and anti-bacterial antibiotics that inhibit protein synthesis kill cancer subtypes enriched for stem cell-like properties.

    Science.gov (United States)

    Cuyàs, Elisabet; Martin-Castillo, Begoña; Corominas-Faja, Bruna; Massaguer, Anna; Bosch-Barrera, Joaquim; Menendez, Javier A

    2015-01-01

    Key players in translational regulation such as ribosomes might represent powerful, but hitherto largely unexplored, targets to eliminate drug-refractory cancer stem cells (CSCs). A recent study by the Lisanti group has documented how puromycin, an old antibiotic derived from Streptomyces alboniger that inhibits ribosomal protein translation, can efficiently suppress CSC states in tumorspheres and monolayer cultures. We have used a closely related approach based on Biolog Phenotype Microarrays (PM), which contain tens of lyophilized antimicrobial drugs, to assess the chemosensitivity profiles of breast cancer cell lines enriched for stem cell-like properties. Antibiotics directly targeting active sites of the ribosome including emetine, puromycin and cycloheximide, inhibitors of ribosome biogenesis such as dactinomycin, ribotoxic stress agents such as daunorubicin, and indirect inhibitors of protein synthesis such as acriflavine, had the largest cytotoxic impact against claudin-low and basal-like breast cancer cells. Thus, biologically aggressive, treatment-resistant breast cancer subtypes enriched for stem cell-like properties exhibit exacerbated chemosensitivities to anti-protozoal and anti-bacterial antibiotics targeting protein synthesis. These results suggest that old/existing microbicides might be repurposed not only as new cancer therapeutics, but also might provide the tools and molecular understanding needed to develop second-generation inhibitors of ribosomal translation to eradicate CSC traits in tumor tissues.

  16. Increasing Breast Cancer Surveillance among African American Breast Cancer Survivors

    National Research Council Canada - National Science Library

    Thompson, Hayley

    2005-01-01

    ...; they also are at considerable risk for breast cancer recurrence. According to the American Society of Clinical Oncology, survivors should undergo careful breast cancer surveillance, including annual mammography and breast self-exam...

  17. Breast asymmetry and predisposition to breast cancer

    OpenAIRE

    Scutt, Diane; Lancaster, Gillian A; Manning, John T

    2006-01-01

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

  18. Maintenance of prolactin receptors in human breast cancer

    International Nuclear Information System (INIS)

    Ben-David, M.; Dror, Y.; Biran, S.

    1981-01-01

    Breast tissue specimens of 110 women with various stages of breast cancer were tested in vitro to determine their specific binding sites for human prolactin. In contrast to the case of steroid receptors, binding sites for prolactin were found in the vast majority of breast cancer tissue. Distribution profiles giving amount of prolactin receptor and their affinity coefficients were found to be similar in the tissues of women whose ages, hormonal status, or stage of breast cancer varied. These findings show that in contrast to steroid receptors, human breast cancer tissue maintains binding sites for prolactin. The findings also indicate that there may be a higher dependency of breast cancer on prolactin than on steroids. Clinical trials must be carried out to determine the role of ''positive'' prolactin receptors in prognosis and prediction of response to future hormone therapy. (author)

  19. Obesity-associated Breast Cancer: Analysis of risk factors.

    Science.gov (United States)

    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.

  20. Clinical outcome of percutaneous RF-ablation of non-operable patients with liver metastasis from breast cancer

    DEFF Research Database (Denmark)

    Kümler, Iben; Parner, Vibeke Kirk; Tuxen, Malgorzata K.

    2015-01-01

    PURPOSE: Despite improved anti-neoplastic treatment the prognosis for patients with liver metastases from metastatic breast cancer remains poor. MATERIALS AND METHODS: Thirty-two consecutive patients with metastatic breast cancer treated with radiofrequency ablation (RFA) at the Department of Onc...

  1. Polymeric Nano-Encapsulation of Curcumin Enhances its Anti-Cancer Activity in Breast (MDA-MB231) and Lung (A549) Cancer Cells Through Reduction in Expression of HIF-1α and Nuclear p65 (Rel A).

    Science.gov (United States)

    Khan, Mohammed N; Haggag, Yusuf A; Lane, Majella E; McCarron, Paul A; Tambuwala, Murtaza M

    2018-02-14

    The anti-cancer potential of curcumin, a natural NFκβ inhibitor, has been reported extensively in breast, lung and other cancers. In vitro and in vivo studies indicate that the therapeutic efficacy of curcumin is enhanced when formulated in a nanoparticulate carrier. However, the mechanism of action of curcumin at the molecular level in the hypoxic tumour micro-environment is not fully understood. Hence, the aim of our study was to investigate the mechanism of action of curcumin formulated as nanoparticles in in vitro models of breast and lung cancer under an hypoxic microenvironment. Biodegradable poly(lactic-co-glycolic acid) PLGA nanoparticles (NP), loaded with curcumin (cur-PLGA-NP), were fabricated using a solvent evaporation technique to overcome solubility issues and to facilitate intracellular curcumin delivery. Cytotoxicity of free curcumin and cur-PLGA-NP was evaluated in MDA-MB-231 and A549 cell lines using migration, invasion and colony formation assays. All treatments were performed under an hypoxic micro-environment and whole cell lysates from controls and test groups were used to determine the expression of HIF-1α and p65 levels using ELISA assays. A ten-fold increase in solubility, three-fold increase in anti-cancer activity and a significant reduction in the levels of cellular HIF-1α and nuclear p65 (Rel A) were observed for cur-PLGA-NP, when compared to free curcumin. Our findings indicate that curcumin can effectively lower the elevated levels of HIF-1α and nuclear p65 (Rel A) in breast and lung cancer cells under an hypoxic tumour micro-environment when delivered in nanoparticulate form. This applied means of colloidal delivery could explain the improved anti-cancer efficacy of curcumin and has further potential applications in enhancing the activity of anti-cancer agents of low solubility. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  2. Breast MRI, digital mammography and breast tomosynthesis: comparison of three methods for early detection of breast cancer.

    Science.gov (United States)

    Roganovic, Dragana; Djilas, Dragana; Vujnovic, Sasa; Pavic, Dag; Stojanov, Dragan

    2015-11-16

    Breast cancer is the most common malignancy in women and early detection is important for its successful treatment. The aim of this study was to investigate the sensitivity and specificity of three methods for early detection of breast cancer: breast magnetic resonance imaging (MRI), digital mammography, and breast tomosynthesis in comparison to histopathology, as well as to investigate the intraindividual variability between these modalities. We included 57 breast lesions, each detected by three diagnostic modalities: digital mammography, breast MRI, and breast tomosynthesis, and subsequently confirmed by histopathology. Breast Imaging-Reporting and Data System (BI-RADS) was used for characterizing the lesions. One experienced radiologist interpreted all three diagnostic modalities. Twenty-nine of the breast lesions were malignant while 28 were benign. The sensitivity for digital mammography, breast MRI, and breast tomosynthesis, was 72.4%, 93.1%, and 100%, respectively; while the specificity was 46.4%, 60.7%, and 75%, respectively. Receiver operating characteristics (ROC) curve analysis showed an overall diagnostic advantage of breast tomosynthesis over both breast MRI and digital mammography. The difference in performance between breast tomosynthesis and digital mammography was significant (p tomosynthesis and breast MRI was not significant (p=0.20).

  3. The Effect of Breast Cancer Fatalism on Breast Cancer Awareness Among Turkish Women.

    Science.gov (United States)

    Altintas, Hulya Kulakci; Ayyildiz, Tulay Kuzlu; Veren, Funda; Topan, Aysel Kose

    2017-10-01

    The aim of this study was to evaluate the effect of breast cancer fatalism and other factors on breast cancer awareness among Turkish women. This cross-sectional and comparative descriptive study was conducted with 894 women. Data were collected by Personal Information Form, Powe Fatalism Inventory and Champion's Health Belief Model Scale. Seriousness, health motivation, BSE benefits and BSE self-efficacy perceptions of the women were moderate, and susceptibility and BSE barriers perceptions were low. It was determined that awareness of breast cancer of the women was affected by breast cancer fatalism, age, education level, employment status, marital status, family type, economic status, social assurance, menopause status, family history of cancer, family history of breast cancer, knowledge on BSE, source of information on BSE, performing of BSE, frequency of BSE performing, having a problem with breast, having a breast examination in hospital, feeling during breast examination by healthcare professional, sex of healthcare professional for breast examination and their health beliefs (p breast cancer of the women was affected by breast cancer fatalism. In providing breast cancer early diagnosis behaviors, it is recommended to evaluate fatalism perceptions and health beliefs of the women and to arrange educational programs for this purpose.

  4. Diet and breast cancer: understanding risks and benefits.

    Science.gov (United States)

    Thomson, Cynthia A

    2012-10-01

    Breast cancer is the most commonly diagnosed cancer among women in the United States. Extensive research has been completed to evaluate the relationship between dietary factors and breast cancer risk and survival after breast cancer; however, a summary report with clinical inference is needed. Materials and This review summarizes the current epidemiological and clinical trial evidence relating diet to breast cancer incidence, recurrence, survival, and mortality. The review includes emerging epidemiological studies that assess risk within breast cancer subtypes as well as a summary of previous and ongoing dietary intervention trials designed to modify breast cancer risk. The available literature suggests that both low-fat and high-fiber diets may be weakly protective against breast cancer, whereas total energy intake and alcohol appear to be positively associated. Fiber may be weakly protective possibly through modulation of estrogen, whereas fruit and vegetable intake is not clearly associated with risk. Obesity is a risk factor for postmenopausal disease, and adult weight gain should be avoided to reduce risk. In survivors, diet has the greatest potential influence on overall mortality rather than breast cancer-specific events. Diet is modestly associated with breast cancer risk; associations appear more pronounced for postmenopausal disease, and healthy choices after diagnosis and treatment likely support longevity more so than reduced risk for recurrent disease.

  5. G-CSF regulates macrophage phenotype and associates with poor overall survival in human triple-negative breast cancer

    Science.gov (United States)

    Hollmén, Maija; Karaman, Sinem; Schwager, Simon; Lisibach, Angela; Christiansen, Ailsa J.; Maksimow, Mikael; Varga, Zsuzsanna; Jalkanen, Sirpa; Detmar, Michael

    2016-01-01

    ABSTRACT Tumor-associated macrophages (TAMs) have been implicated in the promotion of breast cancer growth and metastasis, and a strong infiltration by TAMs has been associated with estrogen receptor (ER)-negative tumors and poor prognosis. However, the molecular mechanisms behind these observations are unclear. We investigated macrophage activation in response to co-culture with several breast cancer cell lines (T47D, MCF-7, BT-474, SKBR-3, Cal-51 and MDA-MB-231) and found that high granulocyte colony-stimulating factor (G-CSF) secretion by the triple-negative breast cancer (TNBC) cell line MDA-MB-231 gave rise to immunosuppressive HLA-DRlo macrophages that promoted migration of breast cancer cells via secretion of TGF-α. In human breast cancer samples (n = 548), G-CSF was highly expressed in TNBC (p CSF blockade in the 4T1 mammary tumor model promoted maturation of MHCIIhi blood monocytes and TAMs and significantly reduced lung metastasis, anti-CSF-1R treatment promoted MHCIIloF4/80hiMRhi anti-inflammatory TAMs and enhanced lung metastasis in the presence of high G-CSF levels. Combined anti-G-CSF and anti-CSF-1R therapy significantly increased lymph node metastases, possibly via depletion of the so-called “gate-keeper” subcapsular sinus macrophages. These results indicate that G-CSF promotes the anti-inflammatory phenotype of tumor-induced macrophages when CSF-1R is inhibited and therefore caution against the use of M-CSF/CSF-1R targeting agents in tumors with high G-CSF expression. PMID:27141367

  6. The aluminium content of breast tissue taken from women with breast cancer.

    Science.gov (United States)

    House, Emily; Polwart, Anthony; Darbre, Philippa; Barr, Lester; Metaxas, George; Exley, Christopher

    2013-10-01

    The aetiology of breast cancer is multifactorial. While there are known genetic predispositions to the disease it is probable that environmental factors are also involved. Recent research has demonstrated a regionally specific distribution of aluminium in breast tissue mastectomies while other work has suggested mechanisms whereby breast tissue aluminium might contribute towards the aetiology of breast cancer. We have looked to develop microwave digestion combined with a new form of graphite furnace atomic absorption spectrometry as a precise, accurate and reproducible method for the measurement of aluminium in breast tissue biopsies. We have used this method to test the thesis that there is a regional distribution of aluminium across the breast in women with breast cancer. Microwave digestion of whole breast tissue samples resulted in clear homogenous digests perfectly suitable for the determination of aluminium by graphite furnace atomic absorption spectrometry. The instrument detection limit for the method was 0.48 μg/L. Method blanks were used to estimate background levels of contamination of 14.80 μg/L. The mean concentration of aluminium across all tissues was 0.39 μg Al/g tissue dry wt. There were no statistically significant regionally specific differences in the content of aluminium. We have developed a robust method for the precise and accurate measurement of aluminium in human breast tissue. There are very few such data currently available in the scientific literature and they will add substantially to our understanding of any putative role of aluminium in breast cancer. While we did not observe any statistically significant differences in aluminium content across the breast it has to be emphasised that herein we measured whole breast tissue and not defatted tissue where such a distribution was previously noted. We are very confident that the method developed herein could now be used to provide accurate and reproducible data on the aluminium content

  7. Breast cancer in men

    Science.gov (United States)

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

  8. Characterization of IKBKE as a Breast Cancer Oncogene

    Science.gov (United States)

    2011-10-01

    HMLE -MEKDD cells stably expressing either pWZL or MF-IKKε. Immunoblot analysis by IKKε antibody. (D) IP with an IKK antibody from MCF-7 breast cancer ...summary is presented of research performed during three years of a project to further characterize the breast cancer oncogene IKKε. Two specific aims...constitutive IKKε transgenic mouse model to study the role of IKKε in breast cancer initiation and maintenance. The long term goals of this research

  9. Inhibition of autophagy enhances the cytotoxic effect of PA-MSHA in breast cancer

    International Nuclear Information System (INIS)

    Xu, Wen-Huan; Liu, Zhe-Bin; Hou, Yi-Feng; Hong, Qi; Hu, Da-Li; Shao, Zhi-Ming

    2014-01-01

    PA-MSHA, a genetically engineered Pseudomonas aeruginosa (PA) strain, is currently under investigation as a new anti-cancer drug. It can induce cell cycle arrest and apoptosis in different human cancer cells, including hormone receptor negative breast cancer cells. However, the underlying mechanism of tumor lethality mediated by PA-MSHA remains to be fully investigated. The effect of PA-MSHA on human hormone receptor negative breast cancer cells was analyzed by morphological measurement, western blot, cell proliferation assay and mouse xenograft model. PA-MSHA was found to induce endoplasmic reticulum (ER) stress in breast cancer cell lines through the IRE1 signaling pathway. Inhibiting autophagy potentiated the cytotoxic effect of PA-MSHA while treating breast cancer cell lines. In mouse xenograft model, PA-MSHA produced more pronounced tumor suppression in mice inoculated with IRE1 gene knockdown. MDA-MB-231HM cells. These findings demonstrated inhibiting autophagy together with PA-MSHA might be a promising therapeutic strategy in treating hormone receptor negative breast cancer cells

  10. Evaluation of Stem Cell Markers, CD44/CD24 in Breast Cancer Cell Lines

    Directory of Open Access Journals (Sweden)

    Masoud Hashemi Arabi

    2014-05-01

    Four breast cancer cell lines, MCF-7 ، T47D ، MDA-MB231 and MDA-MB468 were purchased from National cell Bank of Iran based in Iran Pasture Institute and were cultured in high glucose DMEM supplemented with 10% FCS. Cells were stained with antiCD44-PE and antiCD24-FITC antibodies and Status of CD44 and CD24 as markers of breast cancer stem cells were evaluated using flow cytometer and fluorescent microscopy.Evaluation of CD44 and CD24 as markers of breast cancer stem cells showed that MDA-MB231 with 97±1.2% CD44+/CD24-/low cells is significantly different from the others that they were mainly CD44 and CD24 positive cells(p

  11. Application of PET in breast cancer

    International Nuclear Information System (INIS)

    Noh, Dong Young

    2002-01-01

    Positron emission tomography (PET) is an imaging method that employs radionuclide and tomography techniques. Since 1995, we applied PET not only to the diagnosis of breast cancer but also to the detection of abnormalities in the augmented breast and to the detection of metastasis. Until 2001, we evaluated 242 breast cases by PET at PET center of Seoul National University Hospital. Our group has reported serially at the international journals. In the firtst report, PET showed high sensitivity for detecting breast cancer, both the primary and axillary node metastasis. A total of 27 patients underwent breast operations based on PET results at Seoul National University Hospital from 1995 to 1996. The diagnostic accuracy of PET were 97% for the primary tumor mass and 96% for axillary lymph node metastasis. In case of the breast augmented, PET also showed excellent diagnostic results for primary breast cancer and axillary lymph node metastasis where mammography and ultrasound could not diagnose properly. PET also had outstanding results in the detection of recurrent or metastatic breast cancer(sensitivity 94%, specificity 80%, accuracy 89%). In addition, our study gave some evidence that PET could be applied further to evaluate the growth rate of tumors by measuring SUV, and finally to prognosticated the disease. PET could also be applied to evaluate the response after chemotherapy to measure its metabolic rate and size. In conclsion, PET is a highly sensitive, accurate diagnostic tool for breast cancer of primary lesion in various conditions including metastasis

  12. Potential Anti-Inflammatory Effects of the Hydrophilic Fraction of Pomegranate (Punica granatum L. Seed Oil on Breast Cancer Cell Lines

    Directory of Open Access Journals (Sweden)

    Susan Costantini

    2014-06-01

    Full Text Available In this work, we characterized conjugated linolenic acids (e.g., punicic acid as the major components of the hydrophilic fraction (80% aqueous methanol extract from pomegranate (Punica granatum L. seed oil (PSO and evaluated their anti-inflammatory potential on some human colon (HT29 and HCT116, liver (HepG2 and Huh7, breast (MCF-7 and MDA-MB-231 and prostate (DU145 cancer lines. Our results demonstrated that punicic acid and its congeners induce a significant decrease of cell viability for two breast cell lines with a related increase of the cell cycle G0/G1 phase respect to untreated cells. Moreover, the evaluation of a great panel of cytokines expressed by MCF-7 and MDA-MB-231 cells showed that the levels of VEGF and nine pro-inflammatory cytokines (IL-2, IL-6, IL-12, IL-17, IP-10, MIP-1α, MIP-1β, MCP-1 and TNF-α decreased in a dose dependent way with increasing amounts of the hydrophilic extracts of PSO, supporting the evidence of an anti-inflammatory effect. Taken together, the data herein suggest a potential synergistic cytotoxic, anti-inflammatory and anti-oxidant role of the polar compounds from PSO.

  13. Production and characterisation of monoclonal antibodies against RAI3 and its expression in human breast cancer

    International Nuclear Information System (INIS)

    Jörißen, Hannah; Klockenbring, Torsten; Bektas, Nuran; Dahl, Edgar; Hartmann, Arndt; Haaf, Anette ten; Di Fiore, Stefano; Kiefer, Hans; Thess, Andreas; Barth, Stefan

    2009-01-01

    RAI3 is an orphan G-protein coupled receptor (GPCR) that has been associated with malignancy and may play a role in the proliferation of breast cancer cells. Although its exact function in normal and malignant cells remains unclear and evidence supporting its role in oncogenesis is controversial, its abundant expression on the surface of cancer cells would make it an interesting target for the development of antibody-based therapeutics. To investigate the link with cancer and provide more evidence for its role, we carried out a systematic analysis of RAI3 expression in a large set of human breast cancer specimens. We expressed recombinant human RAI3 in bacteria and reconstituted the purified protein in liposomes to raise monoclonal antibodies using classical hybridoma techniques. The specific binding activity of the antibodies was confirmed by enzyme-linked immunosorbent assay (ELISA), western blot and immunocytochemistry. We carried out a systematic immunohistochemical analysis of RAI3 expression in human invasive breast carcinomas (n = 147) and normal breast tissues (n = 44) using a tissue microarray. In addition, a cDNA dot blot hybridisation assay was used to investigate a set of matched normal and cancerous breast tissue specimens (n = 50) as well as lymph node metastases (n = 3) for RAI3 mRNA expression. The anti-RAI3 monoclonal antibodies bound to recombinant human RAI3 protein with high specificity and affinity, as shown by ELISA, western blot and ICC. The cDNA dot blot and immunohistochemical experiments showed that both RAI3 mRNA and RAI3 protein were abundantly expressed in human breast carcinoma. However, there was no association between RAI3 protein expression and prognosis based on overall and recurrence-free survival. We have generated a novel, highly-specific monoclonal antibody that detects RAI3 in formaldehyde-fixed paraffin-embedded tissue. This is the first study to report a systematic analysis of RAI3 expression in normal and cancerous human

  14. Specific expression of the human voltage-gated proton channel Hv1 in highly metastatic breast cancer cells, promotes tumor progression and metastasis

    International Nuclear Information System (INIS)

    Wang, Yifan; Li, Shu Jie; Pan, Juncheng; Che, Yongzhe; Yin, Jian; Zhao, Qing

    2011-01-01

    Highlights: → Hv1 is specifically expressed in highly metastatic human breast tumor tissues. → Hv1 regulates breast cancer cytosolic pH. → Hv1 acidifies extracellular milieu. → Hv1 exacerbates the migratory ability of metastatic cells. -- Abstract: The newly discovered human voltage-gated proton channel Hv1 is essential for proton transfer, which contains a voltage sensor domain (VSD) without a pore domain. We report here for the first time that Hv1 is specifically expressed in the highly metastatic human breast tumor tissues, but not in poorly metastatic breast cancer tissues, detected by immunohistochemistry. Meanwhile, real-time RT-PCR and immunocytochemistry showed that the expression levels of Hv1 have significant differences among breast cancer cell lines, MCF-7, MDA-MB-231, MDA-MB-468, MDA-MB-453, T-47D and SK-BR-3, in which Hv1 is expressed at a high level in highly metastatic human breast cancer cell line MDA-MB-231, but at a very low level in poorly metastatic human breast cancer cell line MCF-7. Inhibition of Hv1 expression in the highly metastatic MDA-MB-231 cells by small interfering RNA (siRNA) significantly decreases the invasion and migration of the cells. The intracellular pH of MDA-MB-231 cells down-regulated Hv1 expression by siRNA is obviously decreased compared with MDA-MB-231 with the scrambled siRNA. The expression of matrix metalloproteinase-2 and gelatinase activity in MDA-MB-231 cells suppressed Hv1 by siRNA were reduced. Our results strongly suggest that Hv1 regulates breast cancer intracellular pH and exacerbates the migratory ability of metastatic cells.

  15. Anti-Cancer Activity of Methanol Extracts of Cichorium Intybus on Human Breast Cancer SKBR3 Cell Line

    Directory of Open Access Journals (Sweden)

    Reza Mehrandish

    2016-11-01

    Full Text Available Background Breast cancer is the most prevalent cancer and the second cause of death among women around the world. In many cancers, including breast cancer, Fatty acid synthase (FASN gene expression is increased significantly. In breast cancer cell lines, expression of FASN is higher in HER2 positive cell line like SKBR3 than the others. FASN is the key enzyme for fatty acid synthesis de novo pathway and it is producing palmitate which is necessary for cell membrane formation. Cichorium intybus is a medicinal plant that effectively leads to inhibition of fatty acid synthase and thus reduces the percentage of survival of cancer cell lines. Objectives The aim of this study was to evaluate the effect of methanol extract of Chicorium intybus root on percentage of survival in SKBR3 cell line. Methods Human breast cancer SKBR3 cell line was cultured in DMEM medium. Methanol extract of Cichorium intybus root was extracted and different dilutions (200, 300, 400, 500 and 600µg/mL were added to cell culture. Cell viability was quantitated by MTT assay after 24, 48 and 72 hours. Results Cichorium intybus could decrease cell viability. The effects of extract on cell viability were observed after 24, 48 and 72 hours on SKBR3 cell line and IC50 was 800, 400 and 300 after 24, 48 and 72 hours of treatment, respectively. Conclusions Our study shows that methanol extract of Cichorium intybus has cytotoxic effects on tumor cells. This is a pilot work for further evaluation in the future.

  16. Do breast implants adversely affect prognosis among those subsequently diagnosed with breast cancer? Findings from an extended follow-up of a Canadian cohort.

    Science.gov (United States)

    Lavigne, Eric; Holowaty, Eric J; Pan, Sai Yi; Xie, Lin; Villeneuve, Paul J; Morrison, Howard; Brisson, Jacques

    2012-10-01

    Cosmetic breast implants may impair the ability to detect breast cancers. The aims of this study were to examine whether implants and implant characteristics are associated with more advanced breast tumors at diagnosis and poorer survival. Study population includes all invasive breast cancer cases diagnosed during follow-up of the large Canadian Breast Implant Cohort. A total of 409 women with cosmetic breast implants and 444 women with other cosmetic surgery were diagnosed with breast cancer. These women were compared for stage at diagnosis using multinomial logistic regression models. Cox proportional hazards regression models were used for breast cancer-specific mortality analyses. Comparisons were also conducted according to implant characteristics. Compared with women with other cosmetic surgery, those with cosmetic breast implants had at later stage breast cancer diagnosis (OR of having stage III/IV vs. stage I at diagnosis: 3.04, 95% confidence interval (CI): 1.81-5.10; P breast cancer-specific mortality rate for women with breast implants relative to surgical controls was observed (HR = 1.32, 95% CI: 0.94-1.83, P = 0.11). No statistically significant differences in stage and breast cancer mortality were observed according to implant characteristics. At diagnosis, breast cancers tended to be at more advanced stages among women with cosmetic breast implants. Breast cancer-specific survival was lower in these women although the reduction did not reach statistical significance. Further investigations of the effect of breast implants on breast cancer prognosis are warranted. 2012 AACR

  17. Breast cancer prevention.

    Science.gov (United States)

    Euhus, David M; Diaz, Jennifer

    2015-01-01

    Breast cancer is the most common cancer in women with 232,670 new cases estimated in the USA for 2014. Approaches for reducing breast cancer risk include lifestyle modification, chemoprevention, and prophylactic surgery. Lifestyle modification has a variety of health benefits with few associated risks and is appropriate for all women regardless of breast cancer risk. Chemoprevention options have expanded rapidly, but most are directed at estrogen receptor positive breast cancer and uptake is low. Prophylactic surgery introduces significant additional risks of its own and is generally reserved for the highest risk women. © 2014 Wiley Periodicals, Inc.

  18. MR-Guided High-Intensity Focused Ultrasound Ablation of Breast Cancer with a Dedicated Breast Platform

    International Nuclear Information System (INIS)

    Merckel, Laura G.; Bartels, Lambertus W.; Köhler, Max O.; Bongard, H. J. G. Desirée van den; Deckers, Roel; Mali, Willem P. Th. M.; Binkert, Christoph A.; Moonen, Chrit T.; Gilhuijs, Kenneth G. A.; Bosch, Maurice A. A. J. van den

    2013-01-01

    Optimizing the treatment of breast cancer remains a major topic of interest. In current clinical practice, breast-conserving therapy is the standard of care for patients with localized breast cancer. Technological developments have fueled interest in less invasive breast cancer treatment. Magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) is a completely noninvasive ablation technique. Focused beams of ultrasound are used for ablation of the target lesion without disrupting the skin and subcutaneous tissues in the beam path. MRI is an excellent imaging method for tumor targeting, treatment monitoring, and evaluation of treatment results. The combination of HIFU and MR imaging offers an opportunity for image-guided ablation of breast cancer. Previous studies of MR-HIFU in breast cancer patients reported a limited efficacy, which hampered the clinical translation of this technique. These prior studies were performed without an MR-HIFU system specifically developed for breast cancer treatment. In this article, a novel and dedicated MR-HIFU breast platform is presented. This system has been designed for safe and effective MR-HIFU ablation of breast cancer. Furthermore, both clinical and technical challenges are discussed, which have to be solved before MR-HIFU ablation of breast cancer can be implemented in routine clinical practice.

  19. Breast cancer stem-like cells are inhibited by a non-toxic aryl hydrocarbon receptor agonist.

    Directory of Open Access Journals (Sweden)

    Gérald J Prud'homme

    2010-11-01

    Full Text Available Cancer stem cells (CSCs have increased resistance to cancer chemotherapy. They can be enriched as drug-surviving CSCs (D-CSCs by growth with chemotherapeutic drugs, and/or by sorting of cells expressing CSC markers such as aldehyde dehydrogenase-1 (ALDH. CSCs form colonies in agar, mammospheres in low-adherence cultures, and tumors following xenotransplantation in Scid mice. We hypothesized that tranilast, a non-toxic orally active drug with anti-cancer activities, would inhibit breast CSCs.We examined breast cancer cell lines or D-CSCs generated by growth of these cells with mitoxantrone. Tranilast inhibited colony formation, mammosphere formation and stem cell marker expression. Mitoxantrone-selected cells were enriched for CSCs expressing stem cell markers ALDH, c-kit, Oct-4, and ABCG2, and efficient at forming mammospheres. Tranilast markedly inhibited mammosphere formation by D-CSCs and dissociated formed mammospheres, at pharmacologically relevant concentrations. It was effective against D-CSCs of both HER-2+ and triple-negative cell lines. Tranilast was also effective in vivo, since it prevented lung metastasis in mice injected i.v. with triple-negative (MDA-MB-231 mitoxantrone-selected cells. The molecular targets of tranilast in cancer have been unknown, but here we demonstrate it is an aryl hydrocarbon receptor (AHR agonist and this plays a key role. AHR is a transcription factor activated by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, polycyclic aromatic hydrocarbons and other ligands. Tranilast induced translocation of the AHR to the nucleus and stimulated CYP1A1 expression (a marker of AHR activation. It inhibited binding of the AHR to CDK4, which has been linked to cell-cycle arrest. D-CSCs expressed higher levels of the AHR than other cells. Knockdown of the AHR with siRNA, or blockade with an AHR antagonist, entirely abrogated the anti-proliferative and anti-mammosphere activity of tranilast. Thus, the anti-cancer effects of

  20. Extensions of the Rosner-Colditz breast cancer prediction model to include older women and type-specific predicted risk.

    Science.gov (United States)

    Glynn, Robert J; Colditz, Graham A; Tamimi, Rulla M; Chen, Wendy Y; Hankinson, Susan E; Willett, Walter W; Rosner, Bernard

    2017-08-01

    A breast cancer risk prediction rule previously developed by Rosner and Colditz has reasonable predictive ability. We developed a re-fitted version of this model, based on more than twice as many cases now including women up to age 85, and further extended it to a model that distinguished risk factor prediction of tumors with different estrogen/progesterone receptor status. We compared the calibration and discriminatory ability of the original, the re-fitted, and the type-specific models. Evaluation used data from the Nurses' Health Study during the period 1980-2008, when 4384 incident invasive breast cancers occurred over 1.5 million person-years. Model development used two-thirds of study subjects and validation used one-third. Predicted risks in the validation sample from the original and re-fitted models were highly correlated (ρ = 0.93), but several parameters, notably those related to use of menopausal hormone therapy and age, had different estimates. The re-fitted model was well-calibrated and had an overall C-statistic of 0.65. The extended, type-specific model identified several risk factors with varying associations with occurrence of tumors of different receptor status. However, this extended model relative to the prediction of any breast cancer did not meaningfully reclassify women who developed breast cancer to higher risk categories, nor women remaining cancer free to lower risk categories. The re-fitted Rosner-Colditz model has applicability to risk prediction in women up to age 85, and its discrimination is not improved by consideration of varying associations across tumor subtypes.

  1. Breast MRI, digital mammography and breast tomosynthesis: comparison of three methods for early detection of breast cancer

    Directory of Open Access Journals (Sweden)

    Dragana Roganovic

    2015-11-01

    Full Text Available Breast cancer is the most common malignancy in women and early detection is important for its successful treatment. The aim of this study was to investigate the sensitivity and specificity of three methods for early detection of breast cancer: breast magnetic resonance imaging (MRI, digital mammography, and breast tomosynthesis in comparison to histopathology, as well as to investigate the intraindividual variability between these modalities.  We included 57 breast lesions, each detected by three diagnostic modalities: digital mammography, breast MRI, and breast tomosynthesis, and subsequently confirmed by histopathology. Breast Imaging-Reporting and Data System (BI-RADS was used for characterizing the lesions. One experienced radiologist interpreted all three diagnostic modalities. Twenty-nine of the breast lesions were malignant while 28 were benign. The sensitivity for digital mammography, breast MRI, and breast tomosynthesis, was 72.4%, 93.1%, and 100%, respectively; while the specificity was 46.4%, 60.7%, and 75%, respectively. Receiver operating characteristics (ROC curve analysis showed an overall diagnostic advantage of breast tomosynthesis over both breast MRI and digital mammography. The difference in performance between breast tomosynthesis and digital mammography was significant (p < 0.001, while the difference between breast tomosynthesis and breast MRI was not significant (p = 0.20. 

  2. Environmental Polychlorinated Biphenyl Exposure and Breast Cancer Risk: A Meta-Analysis of Observational Studies.

    Directory of Open Access Journals (Sweden)

    Jingwen Zhang

    Full Text Available Association between polychlorinated biphenyl (PCB exposure and breast cancer risk has been widely studied, but the results remain controversial. We performed a meta-analysis to evaluate the evidences from observational studies on PCB exposure and breast cancer risk.Relevant studies with data on internal PCB dose were identified from PubMed, EMBASE, CBM and CNKI databases through November 2014. Multivariable-adjusted odds ratio (OR with 95% confidence intervals (CIs were applied to assess the association between PCB exposure and breast cancer risk. Heterogeneity test, sensitivity analysis, subgroup analysis and publication bias test were also performed. To further explore the association between specific groups of PCB congeners and breast cancer, we examined the PCB congeners classified, according to their structural, biological and pharmacokinetics properties, as group I (potentially estrogenic, group II (potentially anti-estrogenic and immunotoxic, dioxin-like, and group III (phenobarbital, CYP1A and CYP2B inducers, biologically persistent.Of 660 studies screened, 25 studies which met criteria were selected, involving a total of 12866 participants (6088 cases and 6778 controls from eight countries. The results showed that the risk of breast cancer was associated with group II (OR = 1.23, 95% CI: 1.08-1.40 and group III (OR = 1.25, 95% CI: 1.09-1.43 PCBs, but not with group I (OR = 1.10, 95%CI: 0.97-1.24 PCBs or total PCB exposure (OR = 1.09, 95%CI: 0.97-1.22.Our meta-analysis based on the selected studies found group II and group III PCB exposure might contribute to the risk of breast cancer. More studies in developing countries with higher PCB levels are needed, as well as studies to explore the relationships between mixtures of organochlorine compounds and breast cancer risk.

  3. Breast cancer

    OpenAIRE

    Gablerová, Pavlína

    2010-01-01

    In this work the topic of breast cancer treated more generally and mainly focused on risk factors for the development. The theoretical part describes the general knowledge about breast cancer as a stage or treatment. The practical part is to have clarified the risk factors that have some bearing on the diagnosis of breast cancer. What level are involved in the probability of occurrence? Can we eliminate them? As a comparison of risk factors examined in the Czech Republic, England, Australia a...

  4. Breast Cancer Risk Prediction Models

    Science.gov (United States)

    Developing statistical models that estimate the probability of developing breast cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  5. Gene expression analysis in human breast cancer associated blood vessels.

    Directory of Open Access Journals (Sweden)

    Dylan T Jones

    Full Text Available Angiogenesis is essential for solid tumour growth, whilst the molecular profiles of tumour blood vessels have been reported to be different between cancer types. Although presently available anti-angiogenic strategies are providing some promise for the treatment of some cancers it is perhaps not surprisingly that, none of the anti-angiogenic agents available work on all tumours. Thus, the discovery of novel anti-angiogenic targets, relevant to individual cancer types, is required. Using Affymetrix microarray analysis of laser-captured, CD31-positive blood vessels we have identified 63 genes that are upregulated significantly (5-72 fold in angiogenic blood vessels associated with human invasive ductal carcinoma (IDC of the breast as compared with blood vessels in normal human breast. We tested the angiogenic capacity of a subset of these genes. Genes were selected based on either their known cellular functions, their enriched expression in endothelial cells and/or their sensitivity to anti-VEGF treatment; all features implicating their involvement in angiogenesis. For example, RRM2, a ribonucleotide reductase involved in DNA synthesis, was upregulated 32-fold in IDC-associated blood vessels; ATF1, a nuclear activating transcription factor involved in cellular growth and survival was upregulated 23-fold in IDC-associated blood vessels and HEX-B, a hexosaminidase involved in the breakdown of GM2 gangliosides, was upregulated 8-fold in IDC-associated blood vessels. Furthermore, in silico analysis confirmed that AFT1 and HEX-B also were enriched in endothelial cells when compared with non-endothelial cells. None of these genes have been reported previously to be involved in neovascularisation. However, our data establish that siRNA depletion of Rrm2, Atf1 or Hex-B had significant anti-angiogenic effects in VEGF-stimulated ex vivo mouse aortic ring assays. Overall, our results provide proof-of-principle that our approach can identify a cohort of

  6. Screening and prevention of breast cancer in primary care.

    Science.gov (United States)

    Tice, Jeffrey A; Kerlikowske, Karla

    2009-09-01

    Mammography remains the mainstay of breast cancer screening. There is little controversy that mammography reduces the risk of dying from breast cancer by about 23% among women between the ages of 50 and 69 years, although the harms associated with false-positive results and overdiagnosis limit the net benefit of mammography. Women in their 70s may have a small benefit from screening mammography, but overdiagnosis increases in this age group as do competing causes of death. While new data support a 16% reduction in breast cancer mortality for 40- to 49-year-old women after 10 years of screening, the net benefit is less compelling in part because of the lower incidence of breast cancer in this age group and because mammography is less sensitive and specific in women younger than 50 years. Digital mammography is more sensitive than film mammography in young women with similar specificity, but no improvements in breast cancer outcomes have been demonstrated. Magnetic resonance imaging may benefit the highest risk women. Randomized trials suggest that self-breast examination does more harm than good. Primary prevention with currently approved medications will have a negligible effect on breast cancer incidence. Public health efforts aimed at increasing mammography screening rates, promoting regular exercise in all women, maintaining a healthy weight, limiting alcohol intake, and limiting postmenopausal hormone therapy may help to continue the recent trend of lower breast cancer incidence and mortality among American women.

  7. Activity of mevalonate pathway inhibitors against breast and ovarian cancers in the ATP-based tumour chemosensitivity assay

    International Nuclear Information System (INIS)

    Knight, Louise A; Kurbacher, Christian M; Glaysher, Sharon; Fernando, Augusta; Reichelt, Ralf; Dexel, Susanne; Reinhold, Uwe; Cree, Ian A

    2009-01-01

    Previous data suggest that lipophilic statins such as fluvastatin and N-bisphosphonates such as zoledronic acid, both inhibitors of the mevalonate metabolic pathway, have anti-cancer effects in vitro and in patients. We have examined the effect of fluvastatin alone and in combination with zoledronic acid in the ATP-based tumour chemosensitivity assay (ATP-TCA) for effects on breast and ovarian cancer tumour-derived cells. Both zoledronic acid and fluvastatin showed activity in the ATP-TCA against breast and ovarian cancer, though fluvastatin alone was less active, particularly against breast cancer. The combination of zoledronic acid and fluvastatin was more active than either single agent in the ATP-TCA with some synergy against breast and ovarian cancer tumour-derived cells. Sequential drug experiments showed that pre-treatment of ovarian tumour cells with fluvastatin resulted in decreased sensitivity to zoledronic acid. Addition of mevalonate pathway components with zoledronic acid with or without fluvastatin showed little effect, while mevalonate did reduced inhibition due to fluvastatin. These data suggest that the combination of zoledronic acid and fluvastatin may have activity against breast and ovarian cancer based on direct anti-cancer cell effects. A clinical trial to test this is in preparation

  8. Fibroblast growth factor receptor 4 (FGFR4) and fibroblast growth factor 19 (FGF19) autocrine enhance breast cancer cells survival.

    Science.gov (United States)

    Tiong, Kai Hung; Tan, Boon Shing; Choo, Heng Lungh; Chung, Felicia Fei-Lei; Hii, Ling-Wei; Tan, Si Hoey; Khor, Nelson Tze Woei; Wong, Shew Fung; See, Sze-Jia; Tan, Yuen-Fen; Rosli, Rozita; Cheong, Soon-Keng; Leong, Chee-Onn

    2016-09-06

    Basal-like breast cancer is an aggressive tumor subtype with poor prognosis. The discovery of underlying mechanisms mediating tumor cell survival, and the development of novel agents to target these pathways, is a priority for patients with basal-like breast cancer. From a functional screen to identify key drivers of basal-like breast cancer cell growth, we identified fibroblast growth factor receptor 4 (FGFR4) as a potential mediator of cell survival. We found that FGFR4 mediates cancer cell survival predominantly via activation of PI3K/AKT. Importantly, a subset of basal-like breast cancer cells also secrete fibroblast growth factor 19 (FGF19), a canonical ligand specific for FGFR4. siRNA-mediated silencing of FGF19 or neutralization of extracellular FGF19 by anti-FGF19 antibody (1A6) decreases AKT phosphorylation, suppresses cancer cell growth and enhances doxorubicin sensitivity only in the FGFR4+/FGF19+ breast cancer cells. Consistently, FGFR4/FGF19 co-expression was also observed in 82 out of 287 (28.6%) primary breast tumors, and their expression is strongly associated with AKT phosphorylation, Ki-67 staining, higher tumor stage and basal-like phenotype. In summary, our results demonstrated the presence of an FGFR4/FGF19 autocrine signaling that mediates the survival of a subset of basal-like breast cancer cells and suggest that inactivation of this autocrine loop may potentially serve as a novel therapeutic intervention for future treatment of breast cancers.

  9. Using Twitter for breast cancer prevention: an analysis of breast cancer awareness month

    Science.gov (United States)

    2013-01-01

    Background One in eight women will develop breast cancer in her lifetime. The best-known awareness event is breast cancer awareness month (BCAM). BCAM month outreach efforts have been associated with increased media coverage, screening mammography and online information searching. Traditional mass media coverage has been enhanced by social media. However, there is a dearth of literature about how social media is used during awareness-related events. The purpose of this research was to understand how Twitter is being used during BCAM. Methods This was a cross-sectional, descriptive study. We collected breast cancer- related tweets from 26 September - 12 November 2012, using Twitter’s application programming interface. We classified Twitter users into organizations, individuals, and celebrities; each tweet was classified as an original or a retweet, and inclusion of a mention, meaning a reference to another Twitter user with @username. Statistical methods included ANOVA and chi square. For content analysis, we used computational linguistics techniques, specifically the MALLET implementation of the unsupervised topic modeling algorithm Latent Dirichlet Allocation. Results There were 1,351,823 tweets by 797,827 unique users. Tweets spiked dramatically the first few days then tapered off. There was an average of 1.69 tweets per user. The majority of users were individuals. Nearly all of the tweets were original. Organizations and celebrities posted more often than individuals. On average celebrities made far more impressions; they were also retweeted more often and their tweets were more likely to include mentions. Individuals were more likely to direct a tweet to a specific person. Organizations and celebrities emphasized fundraisers, early detection, and diagnoses while individuals tweeted about wearing pink. Conclusions Tweeting about breast cancer was a singular event. The majority of tweets did not promote any specific preventive behavior. Twitter is being used

  10. Using Twitter for breast cancer prevention: an analysis of breast cancer awareness month.

    Science.gov (United States)

    Thackeray, Rosemary; Burton, Scott H; Giraud-Carrier, Christophe; Rollins, Stephen; Draper, Catherine R

    2013-10-29

    One in eight women will develop breast cancer in her lifetime. The best-known awareness event is breast cancer awareness month (BCAM). BCAM month outreach efforts have been associated with increased media coverage, screening mammography and online information searching. Traditional mass media coverage has been enhanced by social media. However, there is a dearth of literature about how social media is used during awareness-related events. The purpose of this research was to understand how Twitter is being used during BCAM. This was a cross-sectional, descriptive study. We collected breast cancer- related tweets from 26 September - 12 November 2012, using Twitter's application programming interface. We classified Twitter users into organizations, individuals, and celebrities; each tweet was classified as an original or a retweet, and inclusion of a mention, meaning a reference to another Twitter user with @username. Statistical methods included ANOVA and chi square. For content analysis, we used computational linguistics techniques, specifically the MALLET implementation of the unsupervised topic modeling algorithm Latent Dirichlet Allocation. There were 1,351,823 tweets by 797,827 unique users. Tweets spiked dramatically the first few days then tapered off. There was an average of 1.69 tweets per user. The majority of users were individuals. Nearly all of the tweets were original. Organizations and celebrities posted more often than individuals. On average celebrities made far more impressions; they were also retweeted more often and their tweets were more likely to include mentions. Individuals were more likely to direct a tweet to a specific person. Organizations and celebrities emphasized fundraisers, early detection, and diagnoses while individuals tweeted about wearing pink. Tweeting about breast cancer was a singular event. The majority of tweets did not promote any specific preventive behavior. Twitter is being used mostly as a one-way communication tool. To

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

    International Nuclear Information System (INIS)

    Reinbothe, Susann; Larsson, Anna-Maria; Vaapil, Marica; Wigerup, Caroline; Sun, Jianmin; Jögi, Annika; Neumann, Drorit; Rönnstrand, Lars; Påhlman, Sven

    2014-01-01

    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, 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 + ) 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

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

    Energy Technology Data Exchange (ETDEWEB)

    Reinbothe, Susann; Larsson, Anna-Maria; Vaapil, Marica; Wigerup, Caroline [Department of Laboratory Medicine, Translational Cancer Research, Medicon Village, Lund University, SE-223 81 Lund (Sweden); CREATE Health, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv (Israel); Sun, Jianmin [Department of Laboratory Medicine, Translational Cancer Research, Medicon Village, Lund University, SE-223 81 Lund (Sweden); Jögi, Annika [Department of Laboratory Medicine, Translational Cancer Research, Medicon Village, Lund University, SE-223 81 Lund (Sweden); CREATE Health, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv (Israel); Neumann, Drorit [Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv (Israel); Rönnstrand, Lars [Department of Laboratory Medicine, Translational Cancer Research, Medicon Village, Lund University, SE-223 81 Lund (Sweden); Påhlman, Sven, E-mail: sven.pahlman@med.lu.se [Department of Laboratory Medicine, Translational Cancer Research, Medicon Village, Lund University, SE-223 81 Lund (Sweden); CREATE Health, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv (Israel)

    2014-02-28

    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, 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.

  13. Prevention of breast cancer.

    Science.gov (United States)

    Olver, Ian N

    2016-11-21

    Modifiable lifestyle factors may reduce the risk of developing breast cancer. Obesity is associated particularly with post-menopausal breast cancer. Diet is important, and exercise equivalent to running for up to 8 hours each week reduces the risk of breast cancer, both in its own right and through reducing obesity. Alcohol consumption may be responsible for 5.8% of breast cancers in Australia and it is recommended to reduce this to two standard drinks per day. Drinking alcohol and smoking increases the risk for breast cancer and, therefore, it is important to quit tobacco smoking. Prolonged use of combined oestrogen and progesterone hormone replacement therapy and oral contraceptives may increase breast cancer risk and this must be factored into individual decisions about their use. Ionising radiation, either from diagnostic or therapeutic radiation or through occupational exposure, is associated with a high incidence of breast cancer and exposure may be reduced in some cases. Tamoxifen chemoprevention may reduce the incidence of oestrogen receptor positive cancer in 51% of women with high risk of breast cancer. Uncommon but serious side effects include thromboembolism and uterine cancer. Raloxifene, which can also reduce osteoporosis, can be used in post-menopausal women and is not associated with the development of uterine cancer. Surgical prophylaxis with bilateral mastectomy and salpingo-oophorectomy can reduce the risk of breast cancer in patients carrying BRCA1 or BRCA2 mutations. For preventive treatments, mammographic screening can identify other women at high risk.

  14. Identification of a novel aFGF-binding peptide with anti-tumor effect on breast cancer from phage display library

    Energy Technology Data Exchange (ETDEWEB)

    Dai, Xiaoyong; Cai, Cuizan [College of Pharmacy, Jinan University, Guangzhou 510632, Guangdong (China); Xiao, Fei [Department of Pharmacology, School of Medicine, Jinan University, Guangzhou 510632, Guangdong (China); Xiong, Yaoling [College of Pharmacy, Jinan University, Guangzhou 510632, Guangdong (China); Huang, Yadong; Zhang, Qihao [Department of Biopharmaceutical Research and Development Centre, Institute of Biomedicine, Jinan University, Guangzhou 510632, Guangdong (China); Xiang, Qi [College of Pharmacy, Jinan University, Guangzhou 510632, Guangdong (China); Lou, Guofeng [Department of Biopharmaceutical Research and Development Centre, Institute of Biomedicine, Jinan University, Guangzhou 510632, Guangdong (China); Lian, Mengyang [College of Pharmacy, Jinan University, Guangzhou 510632, Guangdong (China); Su, Zhijian, E-mail: tjnuszj@jnu.edu.cn [Department of Biopharmaceutical Research and Development Centre, Institute of Biomedicine, Jinan University, Guangzhou 510632, Guangdong (China); Zheng, Qing, E-mail: tzhengq@jnu.edu.cn [College of Pharmacy, Jinan University, Guangzhou 510632, Guangdong (China)

    2014-03-21

    Highlights: • A specific aFGF-binding peptide AP8 was identified from a phage display library. • AP8 could inhibit aFGF-stimulated cell proliferation in a dose-dependent manner. • AP8 arrested the cell cycle at the G0/G1 phase by suppressing Cyclin D1. • AP8 could block the activation of Erk1/2 and Akt kinase. • AP8 counteracted proliferation and cell cycle via influencing PA2G4 and PCNA. - Abstract: It has been reported that acidic fibroblast growth factor (aFGF) is expressed in breast cancer and via interactions with fibroblast growth factor receptors (FGFRs) to promote the stage and grade of the disease. Thus, aFGF/FGFRs have been considered essential targets in breast cancer therapy. We identified a specific aFGF-binding peptide (AGNWTPI, named AP8) from a phage display heptapeptide library with aFGF after four rounds of biopanning. The peptide AP8 contained two (TP) amino acids identical and showed high homology to the peptides of the 182–188 (GTPNPTL) site of high-affinity aFGF receptor FGFR1. Functional analyses indicated that AP8 specifically competed with the corresponding phage clone A8 for binding to aFGF. In addition, AP8 could inhibit aFGF-stimulated cell proliferation, arrested the cell cycle at the G0/G1 phase by increasing PA2G4 and suppressing Cyclin D1 and PCNA, and blocked the aFGF-induced activation of Erk1/2 and Akt kinase in both breast cancer cells and vascular endothelial cells. Therefore, these results indicate that peptide AP8, acting as an aFGF antagonist, is a promising therapeutic agent for the treatment of breast cancer.

  15. Nanomedicine applications in the treatment of breast cancer: current state of the art.

    Science.gov (United States)

    Wu, Di; Si, Mengjie; Xue, Hui-Yi; Wong, Ho-Lun

    2017-01-01

    Breast cancer is the most common malignant disease in women worldwide, but the current drug therapy is far from optimal as indicated by the high death rate of breast cancer patients. Nanomedicine is a promising alternative for breast cancer treatment. Nanomedicine products such as Doxil ® and Abraxane ® have already been extensively used for breast cancer adjuvant therapy with favorable clinical outcomes. However, these products were originally designed for generic anticancer purpose and not specifically for breast cancer treatment. With better understanding of the molecular biology of breast cancer, a number of novel promising nanotherapeutic strategies and devices have been developed in recent years. In this review, we will first give an overview of the current breast cancer treatment and the updated status of nanomedicine use in clinical setting, then discuss the latest important trends in designing breast cancer nanomedicine, including passive and active cancer cell targeting, breast cancer stem cell targeting, tumor microenvironment-based nanotherapy and combination nanotherapy of drug-resistant breast cancer. Researchers may get insight from these strategies to design and develop nanomedicine that is more tailored for breast cancer to achieve further improvements in cancer specificity, antitumorigenic effect, antimetastasis effect and drug resistance reversal effect.

  16. Stages of Male Breast Cancer

    Science.gov (United States)

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

  17. Integrated microRNA and mRNA signatures associated with survival in triple negative breast cancer.

    Science.gov (United States)

    Cascione, Luciano; Gasparini, Pierluigi; Lovat, Francesca; Carasi, Stefania; Pulvirenti, Alfredo; Ferro, Alfredo; Alder, Hansjuerg; He, Gang; Vecchione, Andrea; Croce, Carlo M; Shapiro, Charles L; Huebner, Kay

    2013-01-01

    Triple negative breast cancer (TNBC) is a heterogeneous disease at the molecular, pathologic and clinical levels. To stratify TNBCs, we determined microRNA (miRNA) expression profiles, as well as expression profiles of a cancer-focused mRNA panel, in tumor, adjacent non-tumor (normal) and lymph node metastatic lesion (mets) tissues, from 173 women with TNBCs; we linked specific miRNA signatures to patient survival and used miRNA/mRNA anti-correlations to identify clinically and genetically different TNBC subclasses. We also assessed miRNA signatures as potential regulators of TNBC subclass-specific gene expression networks defined by expression of canonical signal pathways.Tissue specific miRNAs and mRNAs were identified for normal vs tumor vs mets comparisons. miRNA signatures correlated with prognosis were identified and predicted anti-correlated targets within the mRNA profile were defined. Two miRNA signatures (miR-16, 155, 125b, 374a and miR-16, 125b, 374a, 374b, 421, 655, 497) predictive of overall survival (P = 0.05) and distant-disease free survival (P = 0.009), respectively, were identified for patients 50 yrs of age or younger. By multivariate analysis the risk signatures were independent predictors for overall survival and distant-disease free survival. mRNA expression profiling, using the cancer-focused mRNA panel, resulted in clustering of TNBCs into 4 molecular subclasses with different expression signatures anti-correlated with the prognostic miRNAs. Our findings suggest that miRNAs play a key role in triple negative breast cancer through their ability to regulate fundamental pathways such as: cellular growth and proliferation, cellular movement and migration, Extra Cellular Matrix degradation. The results define miRNA expression signatures that characterize and contribute to the phenotypic diversity of TNBC and its metastasis.

  18. Cost-effectiveness of the Norwegian breast cancer screening program.

    Science.gov (United States)

    van Luijt, P A; Heijnsdijk, E A M; de Koning, H J

    2017-02-15

    The Norwegian Breast Cancer Screening Programme (NBCSP) has a nation-wide coverage since 2005. All women aged 50-69 years are invited biennially for mammography screening. We evaluated breast cancer mortality reduction and performed a cost-effectiveness analysis, using our microsimulation model, calibrated to most recent data. The microsimulation model allows for the comparison of mortality and costs between a (hypothetical) situation without screening and a situation with screening. Breast cancer incidence in Norway had a steep increase in the early 1990s. We calibrated the model to simulate this increase and included recent costs for screening, diagnosis and treatment of breast cancer and travel and productivity loss. We estimate a 16% breast cancer mortality reduction for a cohort of women, invited to screening, followed over their complete lifetime. Cost-effectiveness is estimated at NOK 112,162 per QALY gained, when taking only direct medical costs into account (the cost of the buses, examinations, and invitations). We used a 3.5% annual discount rate. Cost-effectiveness estimates are substantially below the threshold of NOK 1,926,366 as recommended by the WHO guidelines. For the Norwegian population, which has been gradually exposed to screening, breast cancer mortality reduction for women exposed to screening is increasing and is estimated to rise to ∼30% in 2020 for women aged 55-80 years. The NBCSP is a highly cost-effective measure to reduce breast cancer specific mortality. We estimate a breast cancer specific mortality reduction of 16-30%, at the cost of 112,162 NOK per QALY gained. © 2016 UICC.

  19. Alcohol Consumption and Survival after a Breast Cancer Diagnosis

    DEFF Research Database (Denmark)

    Ali, Alaa M G; Schmidt, Marjanka K; Bolla, Manjeet K

    2014-01-01

    BACKGROUND: Evidence for an association of alcohol consumption with prognosis after a diagnosis of breast cancer has been inconsistent. We have reviewed and summarized the published evidence and evaluated the association using individual patient data from multiple case cohorts. METHODS: A MEDLINE...... cancer-specific mortality, with some evidence of a negative association with all-cause mortality. On the basis of a single study, moderate postdiagnosis alcohol intake was associated with a small reduction in breast cancer-specific mortality for women with ER-negative disease. There was no association...... with prediagnosis intake for women with ER-negative disease. CONCLUSION: There was little evidence that pre- or post-diagnosis alcohol consumption is associated with breast cancer-specific mortality for women with ER-positive disease. There was weak evidence that moderate post-diagnosis alcohol intake is associated...

  20. Breast cancer imaging

    International Nuclear Information System (INIS)

    Funke, M.; Villena, C.

    2008-01-01

    Advances in female breast imaging have substantially influenced the diagnosis, therapy, and prognosis of breast cancer in the past few years. Mammography using conventional or digital technique is considered the gold standard for the early detection of breast cancer. Other modalities such as breast ultrasound and contrast-enhanced magnetic resonance imaging of the breast play an important role in diagnostic imaging, staging, and follow-up of breast cancer. Percutaneous needle biopsy is a faster, less invasive, and more cost-effective method than surgical biopsy for verifying the histological diagnosis. New methods such as breast tomosynthesis, contrast-enhanced mammography, and positron emission tomography promise to further improve breast imaging. Further studies are mandatory to adapt these new methods to clinical needs and to evaluate their performance in clinical practice. (orig.) [de

  1. Evaluation of the Cytotoxic and Autophagic Effects of Atorvastatin on MCF-7 Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Tuğba Alarcon Martinez

    2018-05-01

    Full Text Available Background: Recently, cytotoxic effects of statins on breast cancer cells have been reported. However, the mechanism of anti-proliferative effects is currently unknown. Autophagy is non-apoptotic programmed cell death, which is characterized by degradation of cytoplasmic components and as having a role in cancer pathogenesis. Aims: To investigate the anti-proliferative effects of atorvastatin on MCF-7 human breast adenocarcinoma cells with respect to both autophagy and apoptosis. Study Design: Cell culture study. Methods: Cell viability was analyzed using WST-1 cell proliferation assay. Apoptosis was determined by the TUNEL method, whereas autophagy was assessed by Beclin-1 and LC3B immunofluorescence staining. Ultrastructural analysis of cells was performed by electron microscopy. Results: Atorvastatin reduced MCF-7 cell proliferation in a dose- and time-dependent manner inducing TUNEL-, Beclin-1-, and LC3B-positive cells. Moreover, ultrastructural analysis showed apoptotic, autophagic, and necrotic morphological changes in treatment groups. A statistically significant increase in the apoptotic index was detected with higher concentrations of atorvastatin at 24 h and 48 h (p<0.05. Conclusion: The anti-proliferative effects of atorvastatin on breast cancer cells is mediated by the induction of both apoptosis and autophagy which shows statins as a potential treatment option for breast cancer.

  2. Repositioning of antibiotic levofloxacin as a mitochondrial biogenesis inhibitor to target breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Min [Galactophore Department, JingZhou Central Hospital, JingZhou (China); Li, Ruishu, E-mail: liruishu2016@yahoo.com [Forensic Surgery Department, JingZhou Traditional Chinese Medicine Hospital, JingZhou (China); Zhang, Juan [Endocrinology Department, JingZhou Central Hospital, JingZhou (China)

    2016-03-18

    Targeting mitochondrial biogenesis has become a potential therapeutic strategy in cancer due to their unique metabolic dependencies. In this study, we show that levofloxacin, a FDA-approved antibiotic, is an attractive candidate for breast cancer treatment. This is achieved by the inhibition of proliferation and induction of apoptosis in a panel of breast cancer cell lines while sparing normal breast cells. It also acts synergistically with conventional chemo drug in two independent in vivo breast xenograft mouse models. Importantly, levofloxacin inhibits mitochondrial biogenesis as shown by the decreased level of mitochondrial respiration, membrane potential and ATP. In addition, the anti-proliferative and pro-apoptotic effects of levofloxacin are reversed by acetyl-L-Carnitine (ALCAR, a mitochondrial fuel), confirming that levofloxacin's action in breast cancer cells is through inhibition of mitochondrial biogenesis. A consequence of mitochondrial biogenesis inhibition by levofloxacin in breast cancer cells is the deactivation of PI3K/Akt/mTOR and MAPK/ERK pathways. We further demonstrate that breast cancer cells have increased mitochondrial biogenesis than normal breast cells, and this explains their different sensitivity to levofloxacin. Our work suggest that levofloxacin is a useful addition to breast cancer treatment. Our work also establish the essential role of mitochondrial biogenesis on the activation of PI3K/Akt/mTOR and MAPK/ERK pathways in breast cancer cells. - Highlights: • Levofloxacin targets a panel of breast cancer cell lines in vitro and in vivo. • Levofloxacin acts synergistically with 5-Fluorouracil in breast cancer. • Levofloxacin targets breast cancer cells via inhibiting mitochondrial biogenesis. • Breast cancer cells have increased mitochondrial biogenesis than normal cells. • Mitochondrial biogenesis inhibition lead to deactivation of PI3K/Akt/mTOR pathway.

  3. Repositioning of antibiotic levofloxacin as a mitochondrial biogenesis inhibitor to target breast cancer

    International Nuclear Information System (INIS)

    Yu, Min; Li, Ruishu; Zhang, Juan

    2016-01-01

    Targeting mitochondrial biogenesis has become a potential therapeutic strategy in cancer due to their unique metabolic dependencies. In this study, we show that levofloxacin, a FDA-approved antibiotic, is an attractive candidate for breast cancer treatment. This is achieved by the inhibition of proliferation and induction of apoptosis in a panel of breast cancer cell lines while sparing normal breast cells. It also acts synergistically with conventional chemo drug in two independent in vivo breast xenograft mouse models. Importantly, levofloxacin inhibits mitochondrial biogenesis as shown by the decreased level of mitochondrial respiration, membrane potential and ATP. In addition, the anti-proliferative and pro-apoptotic effects of levofloxacin are reversed by acetyl-L-Carnitine (ALCAR, a mitochondrial fuel), confirming that levofloxacin's action in breast cancer cells is through inhibition of mitochondrial biogenesis. A consequence of mitochondrial biogenesis inhibition by levofloxacin in breast cancer cells is the deactivation of PI3K/Akt/mTOR and MAPK/ERK pathways. We further demonstrate that breast cancer cells have increased mitochondrial biogenesis than normal breast cells, and this explains their different sensitivity to levofloxacin. Our work suggest that levofloxacin is a useful addition to breast cancer treatment. Our work also establish the essential role of mitochondrial biogenesis on the activation of PI3K/Akt/mTOR and MAPK/ERK pathways in breast cancer cells. - Highlights: • Levofloxacin targets a panel of breast cancer cell lines in vitro and in vivo. • Levofloxacin acts synergistically with 5-Fluorouracil in breast cancer. • Levofloxacin targets breast cancer cells via inhibiting mitochondrial biogenesis. • Breast cancer cells have increased mitochondrial biogenesis than normal cells. • Mitochondrial biogenesis inhibition lead to deactivation of PI3K/Akt/mTOR pathway.

  4. Decreased Usage of Specific Scrib Exons Defines a More Malignant Phenotype of Breast Cancer With Worsened Survival

    Directory of Open Access Journals (Sweden)

    Gergana Metodieva

    2016-06-01

    Full Text Available SCRIB is a polarity regulator known to be abnormally expressed in cancer at the protein level. Here we report that, in breast cancer, an additional and hidden dimension of deregulations exists: an unexpected SCRIB exon usage pattern appears to mark a more malignant tumor phenotype and significantly correlates with survival. Conserved exons encoding the leucine-rich repeats tend to be overexpressed while others are underused. Mechanistic studies revealed that the underused exons encode part of the protein necessary for interaction with Vimentin and Numa1, a protein which is required for proper positioning of the mitotic spindle. Thus, the inclusion/exclusion of specific SCRIB exons is a mechanistic hallmark of breast cancer, which could potentially be exploited to develop more efficient diagnostics and therapies.

  5. Polypeptide-based nanogels co-encapsulating a synergistic combination of doxorubicin with 17-AAG show potent anti-tumor activity in ErbB2-driven breast cancer models.

    Science.gov (United States)

    Desale, Swapnil S; Raja, Srikumar M; Kim, Jong Oh; Mohapatra, Bhopal; Soni, Kruti S; Luan, Haitao; Williams, Stetson H; Bielecki, Timothy A; Feng, Dan; Storck, Matthew; Band, Vimla; Cohen, Samuel M; Band, Hamid; Bronich, Tatiana K

    2015-06-28

    ErbB2-driven breast cancers constitute 20-25% of the cases diagnosed within the USA. The humanized anti-ErbB2 monoclonal antibody, Trastuzumab (Herceptin™; Genentech), with chemotherapy is the current standard of treatment. Novel agents and strategies continue to be explored, given the challenges posed by Trastuzumab-resistance development in most patients. The HSP90 inhibitor, 17-allylaminodemethoxygeldanamycin (17-AAG), which induces ErbB2 degradation and attenuates downstream oncogenic signaling, is one such agent that showed significant promise in early phase I and II clinical trials. Its low water solubility, potential toxicities and undesirable side effects observed in patients, partly due to the Cremophor-based formulation, have been discouraging factors in the advancement of this promising drug into clinical use. Encapsulation of 17-AAG into polymeric nanoparticle formulations, particularly in synergistic combination with conventional chemotherapeutics, represents an alternative approach to overcome these problems. Herein, we report an efficient co-encapsulation of 17-AAG and doxorubicin, a clinically well-established and effective modality in breast cancer treatment, into biodegradable and biocompatible polypeptide-based nanogels. Dual drug-loaded nanogels displayed potent cytotoxicity in a breast cancer cell panel and exerted selective synergistic anticancer activity against ErbB2-overexpressing breast cancer cell lines. Analysis of ErbB2 degradation confirmed efficient 17-AAG release from nanogels with activity comparable to free 17-AAG. Furthermore, nanogels containing both 17-AAG and doxorubicin exhibited superior antitumor efficacy in vivo in an ErbB2-driven xenograft model compared to the combination of free drugs. These studies demonstrate that polypeptide-based nanogels can serve as novel nanocarriers for encapsulating 17-AAG along with other chemotherapeutics, providing an opportunity to overcome solubility issues and thereby exploit its full

  6. Female breast cancer incidence and mortality in China, 2013

    Science.gov (United States)

    Zuo, Ting‐Ting; Zheng, Rong‐Shou; Zeng, Hong‐Mei; Zhang, Si‐Wei

    2017-01-01

    Background Breast cancer is the most common cancer among women. Population‐based cancer registration data from the National Central Cancer Registry were used to analyze and evaluate the incidence and mortality rates in China in 2013, providing scientific information for cancer prevention and control. Methods Pooled data were stratified by area (urban/rural), gender, and age group. National new cases and deaths were estimated using age‐specific rates and the corresponding population in 2013. The Chinese population in 2000 and Segi's world population were used to calculate age‐standardized rates. Results The estimated number of new breast cancer cases was about 278 800 in China in 2013. The crude incidence, age‐standardized rate of incidence by Chinese standard population, and age‐standardized rate of incidence by world standard population were 42.02/100 000, 30.41/100 000, and 28.42/100 000, respectively. The estimated number of breast cancer deaths was about 64 600 in China in 2013. The crude mortality, age‐standardized rate of mortality by Chinese standard population, and age‐standardized rate of mortality by world standard population were 9.74/100 000, 6.54/100 000, and 6.34/100 000, respectively. Both incidence and mortality were higher in urban than in rural areas. Age‐specific breast cancer incidence significantly increased with age, particularly after age 20, and peaked at 50–55 years, while age‐specific mortality increased rapidly after 25 years, peaking at 85+ years. Conclusions Breast cancer is the most common cancer in Chinese women, especially women in urban areas. Comprehensive measures are needed to reduce the heavy burden of breast cancer. PMID:28296260

  7. Breast Cancer Disparities

    Science.gov (United States)

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

  8. A Methodology for Cancer Therapeutics by Systems Pharmacology-Based Analysis: A Case Study on Breast Cancer-Related Traditional Chinese Medicines.

    Science.gov (United States)

    Li, Yan; Wang, Jinghui; Lin, Feng; Yang, Yinfeng; Chen, Su-Shing

    2017-01-01

    Breast cancer is the most common carcinoma in women. Comprehensive therapy on breast cancer including surgical operation, chemotherapy, radiotherapy, endocrinotherapy, etc. could help, but still has serious side effect and resistance against anticancer drugs. Complementary and alternative medicine (CAM) may avoid these problems, in which traditional Chinese medicine (TCM) has been highlighted. In this section, to analyze the mechanism through which TCM act on breast cancer, we have built a virtual model consisting of the construction of database, oral bioavailability prediction, drug-likeness evaluation, target prediction, network construction. The 20 commonly employed herbs for the treatment of breast cancer were used as a database to carry out research. As a result, 150 ingredient compounds were screened out as active molecules for the herbs, with 33 target proteins predicted. Our analysis indicates that these herbs 1) takes a 'Jun-Chen-Zuo-Shi" as rule of prescription, 2) which function mainly through perturbing three pathways involving the epidermal growth factor receptor, estrogen receptor, and inflammatory pathways, to 3) display the breast cancer-related anti-estrogen, anti-inflammatory, regulation of cell metabolism and proliferation activities. To sum it up, by providing a novel in silico strategy for investigation of the botanical drugs, this work may be of some help for understanding the action mechanisms of herbal medicines and for discovery of new drugs from plants.

  9. A Methodology for Cancer Therapeutics by Systems Pharmacology-Based Analysis: A Case Study on Breast Cancer-Related Traditional Chinese Medicines.

    Directory of Open Access Journals (Sweden)

    Yan Li

    Full Text Available Breast cancer is the most common carcinoma in women. Comprehensive therapy on breast cancer including surgical operation, chemotherapy, radiotherapy, endocrinotherapy, etc. could help, but still has serious side effect and resistance against anticancer drugs. Complementary and alternative medicine (CAM may avoid these problems, in which traditional Chinese medicine (TCM has been highlighted. In this section, to analyze the mechanism through which TCM act on breast cancer, we have built a virtual model consisting of the construction of database, oral bioavailability prediction, drug-likeness evaluation, target prediction, network construction. The 20 commonly employed herbs for the treatment of breast cancer were used as a database to carry out research. As a result, 150 ingredient compounds were screened out as active molecules for the herbs, with 33 target proteins predicted. Our analysis indicates that these herbs 1 takes a 'Jun-Chen-Zuo-Shi" as rule of prescription, 2 which function mainly through perturbing three pathways involving the epidermal growth factor receptor, estrogen receptor, and inflammatory pathways, to 3 display the breast cancer-related anti-estrogen, anti-inflammatory, regulation of cell metabolism and proliferation activities. To sum it up, by providing a novel in silico strategy for investigation of the botanical drugs, this work may be of some help for understanding the action mechanisms of herbal medicines and for discovery of new drugs from plants.

  10. Vitamin C and survival among women with breast cancer: a meta-analysis.

    Science.gov (United States)

    Harris, Holly R; Orsini, Nicola; Wolk, Alicja

    2014-05-01

    The association between dietary vitamin C intake and breast cancer survival is inconsistent and few studies have specifically examined vitamin C supplement use among women with breast cancer. The purpose of this study was to summarise results from prospective studies on the association between vitamin C supplement use and dietary vitamin C intake and breast cancer-specific mortality and total mortality. Studies were identified using the PubMed database through February 6, 2014 and by examining the references of retrieved articles. Prospective studies were included if they reported relative risks (RR) with 95% confidence intervals (95% CIs) for at least two categories or as a continuous exposure. Random-effects models were used to combine study-specific results. The ten identified studies examined vitamin C supplement use (n=6) and dietary vitamin C intake (n=7) and included 17,696 breast cancer cases, 2791 total deaths, and 1558 breast cancer-specific deaths. The summary RR (95% CI) for post-diagnosis vitamin C supplement use was 0.81 (95% CI 0.72-0.91) for total mortality and 0.85 (95% CI 0.74-0.99) for breast cancer-specific mortality. The summary RR for a 100mg per day increase in dietary vitamin C intake was 0.73 (95% CI 0.59-0.89) for total mortality and 0.78 (95% CI 0.64-0.94) for breast cancer-specific mortality. Results from this meta-analysis suggest that post-diagnosis vitamin C supplement use may be associated with a reduced risk of mortality. Dietary vitamin C intake was also statistically significantly associated with a reduced risk of total mortality and breast cancer-specific mortality. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Epidemiological correlates of breast cancer in South India.

    Science.gov (United States)

    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.

  12. Breast cancer

    African Journals Online (AJOL)

    A collaborative article gives an overview of breast cancer in LICs, ... approach to the problem; therefore they are published as two separate ... attached to the diagnosis of breast cancer. ... Their founding statement in its early form is included.

  13. Immunophenotyping invasive breast cancer: paving the road for molecular imaging

    International Nuclear Information System (INIS)

    Vermeulen, Jeroen F; Brussel, Aram SA van; Groep, Petra van der; Morsink, Folkert HM; Bult, Peter; Wall, Elsken van der; Diest, Paul J van

    2012-01-01

    Mammographic population screening in The Netherlands has increased the number of breast cancer patients with small and non-palpable breast tumors. Nevertheless, mammography is not ultimately sensitive and specific for distinct subtypes. Molecular imaging with targeted tracers might increase specificity and sensitivity of detection. Because development of new tracers is labor-intensive and costly, we searched for the smallest panel of tumor membrane markers that would allow detection of the wide spectrum of invasive breast cancers. Tissue microarrays containing 483 invasive breast cancers were stained by immunohistochemistry for a selected set of membrane proteins known to be expressed in breast cancer. The combination of highly tumor-specific markers glucose transporter 1 (GLUT1), epidermal growth factor receptor (EGFR), insulin-like growth factor-1 receptor (IGF1-R), human epidermal growth factor receptor 2 (HER2), hepatocyte growth factor receptor (MET), and carbonic anhydrase 9 (CAIX) 'detected' 45.5% of tumors, especially basal/triple negative and HER2-driven ductal cancers. Addition of markers with a 2-fold tumor-to-normal ratio increased the detection rate to 98%. Including only markers with >3 fold tumor-to-normal ratio (CD44v6) resulted in an 80% detection rate. The detection rate of the panel containing both tumor-specific and less tumor-specific markers was not dependent on age, tumor grade, tumor size, or lymph node status. In search of the minimal panel of targeted probes needed for the highest possible detection rate, we showed that 80% of all breast cancers express at least one of a panel of membrane markers (CD44v6, GLUT1, EGFR, HER2, and IGF1-R) that may therefore be suitable for molecular imaging strategies. This study thereby serves as a starting point for further development of a set of antibody-based optical tracers with a high breast cancer detection rate

  14. Breast cancer screening: Evidence of the effect of adjunct ultrasound screening in women with unilateral mammography-negative dense breasts

    Directory of Open Access Journals (Sweden)

    Atoosa Adibi

    2015-01-01

    Full Text Available Background: Patients with the previous history of breast cancer are in risk of contralateral breast cancer. On the other hand, increased breast density is a risk factor for breast cancer and the sensitivity of detecting nonpalpable cancers in screening mammography in radiographically dense breasts is low. The use of ultrasonography in dense breast remains a controversial topic. The purpose of this study was to assess the usefulness of routine ultrasonography in follow-up of women with the previous history of breast cancer and negative mammography but dense breasts. Materials and Methods: In a cross-sectional study, a total of 267 individuals with unilateral postmastectomy mammogram screened and 153 subjects assigned to study. There were 28 subjects with American College of Radiology (ACR breast density 2 and 125 with ACR breast density 3-4, which there was no new finding in their mammogram in comparison to previous studies. We assumed subjects with ACR breast density 3-4 as mammographic Breast Imaging Reporting and Data System (BI-RADS category 0 for malignancy. Standard two-view mammogram was performed for all participants, and breast ultrasound (US examinations were performed by an expert radiologist in radial and anti-radial planes. The data were analyzed using SPSS version 20.0 (SPSS Inc., Chicago, Illinois, USA. Results: The results showed that in subjects with ACR breast density 3-4, when there was no new density in two consecutive mammograms in comparison to previous studies, US also showed no possibility for malignancy (BI-RADS 1-2. And also in subjects with ACR breast density 2, when the mammographic results were BI-RADS 1-2, the US results was the same. Conclusion: Our data indicate that for the detection of breast cancer, sensitivity of US was not greater than mammography in patients with postmastectomy unilateral dense breast if there is not any new density.

  15. Study of the association between blood types and breast cancer among Isfahanian women with breast cancer

    Directory of Open Access Journals (Sweden)

    Amir Hossein Mirlohi Flavarjani

    2014-01-01

    Conclusion: According to the obtained results from this study, there was no relative frequency in specific blood group for these three types of cancer and the blood type could not be influenced as a risk factor in breast cancer.

  16. DIAGNOSIS OF MUCINOUS BREAST CANCER

    Directory of Open Access Journals (Sweden)

    E. К. Saribekyan

    2014-01-01

    Full Text Available The paper presents the diagnostic results of 27 patients with mucinous breast cancer, which is a rare type of invasive ductal breast cancer accounting for less than 2% of all breast cancers. The role of radiological, histological and cytological examination in the diagnosis of mucinous breast cancer is evaluated. In cases with large tumors, it was difficult to differentiate mucinous breast cancer from fibrocystic and other benign breast lesions.

  17. Radiation as a cause of breast cancer

    International Nuclear Information System (INIS)

    Simon, N.; Silverstone, S.M.

    1976-01-01

    The possible role of radiation as a factor in the causation of breast cancer was investigated. Some variables said to be associated with a high risk of breast cancer include genetic factors, pre-existing breast disease, artificial menopause, family history of breast cancer, failure to breast feed, older than usual age at time of first pregnancy, high socioeconomic status, specific blood groups, fatty diet, obesity, and hormonal imbalances. To this list we must add ionizing radiation as an additional and serious risk factor in the causation of breast cancer. Among the irradiated groups which have an increase in the incidence of cancer of the breast are: tuberculous women subjected to repeated fluoroscopy; women who received localized x-ray treatments for acute post-partum mastitis; atom-bomb survivors; other x-ray exposures involving the breast, including irradiation in children and in experimental animals; and women who were treated with x rays for acne or hirsuitism. The dose of radiation received by the survivors of the atom bomb who subsequently developed cancer of the breast ranged from 80 to 800 rads, the tuberculous women who were fluoroscoped received an estimated 50 to 6,000 rads, the women who were treated for mastitis probably were exposed to 30 to 700 rads, and the patients with acne received 100 to 6,000 rads. These imprecise estimates are compared with mammographic doses in the range of 10s of rads to the breast at each examination, an imprecise estimate depending on technique and equipment. However imprecise these estimates may be, it is apparent that younger women are more likely than older women to develop cancer from exposure to radiation. It is pointed out that the American Cancer Society advises that women under 35 years should have mammography only for medical indication, not for so-called screening

  18. Spectrum of breast cancer in Asian women.

    Science.gov (United States)

    Agarwal, Gaurav; Pradeep, P V; Aggarwal, Vivek; Yip, Cheng-Har; Cheung, Polly S Y

    2007-05-01

    Breast cancer is the leading cause of cancer-related deaths in Asia, and in recent years is emerging as the commonest female malignancy in the developing Asian countries, overtaking cancer of the uterine cervix. There have been no studies objectively comparing data and facts relating to breast cancer in the developed, newly developed, and developing Asian countries thus far. This multi-national collaborative study retrospectively compared the demographic, clinical, pathological and outcomes data in breast cancer patients managed at participating breast cancer centers in India, Malaysia and Hong Kong. Data, including those on the availability of breast screening, treatment facilities and outcomes from other major cancer centers and cancer registries of these countries and from other Asian countries were also reviewed. Despite an increasing trend, the incidence of breast cancer is lower, yet the cause-specific mortality is significantly higher in developing Asian countries compared with developed countries in Asia and the rest of the world. Patients are about one decade younger in developing countries than their counterparts in developed nations. The proportions of young patients (women and the clinical picture are different from those of average patients managed elsewhere in the world. Owing to lack of awareness, lack of funding, lack of infrastructure, and low priority in public health schemes, breast cancer screening and early detection have not caught up in these under-privileged societies. The inadequacies of health care infrastructures and standards, sociocultural barriers, economic realities, illiteracy, and the differences in the clinical and pathological attributes of this disease in Asian women compared with the rest of the world together result in a different spectrum of the disease. Better socioeconomic conditions, health awareness, and availability of breast cancer screening in developed Asian countries seem to be the major causes of a favorable clinical

  19. Symptom report in detecting breast cancer-related lymphedema

    Directory of Open Access Journals (Sweden)

    Fu MR

    2015-10-01

    Full Text Available Mei R Fu,1 Deborah Axelrod,2,3 Charles M Cleland,1 Zeyuan Qiu,4 Amber A Guth,2,3 Robin Kleinman,2 Joan Scagliola,2 Judith Haber1 1College of Nursing, New York University, 2Department of Surgery, NYU School of Medicine, 3NYU Clinical Cancer Center, New York, NY, 4Department of Chemistry and Environmental Science, New Jersey Institute of Technology, Newark, NJ, USA Abstract: Breast cancer-related lymphedema is a syndrome of abnormal swelling coupled with multiple symptoms resulting from obstruction or disruption of the lymphatic system associated with cancer treatment. Research has demonstrated that with increased number of symptoms reported, breast cancer survivors' limb volume increased. Lymphedema symptoms in the affected limb may indicate a latent stage of lymphedema in which changes cannot be detected by objective measures. The latent stage of lymphedema may exist months or years before overt swelling occurs. Symptom report may play an important role in detecting lymphedema in clinical practice. The purposes of this study were to: 1 examine the validity, sensitivity, and specificity of symptoms for detecting breast cancer-related lymphedema and 2 determine the best clinical cutoff point for the count of symptoms that maximized the sum of sensitivity and specificity. Data were collected from 250 women, including healthy female adults, breast cancer survivors with lymphedema, and those at risk for lymphedema. Lymphedema symptoms were assessed using a reliable and valid instrument. Validity, sensitivity, and specificity were evaluated using logistic regression, analysis of variance, and areas under receiver operating characteristic curves. Count of lymphedema symptoms was able to differentiate healthy adults from breast cancer survivors with lymphedema and those at risk for lymphedema. A diagnostic cutoff of three symptoms discriminated breast cancer survivors with lymphedema from healthy women with a sensitivity of 94% and a specificity of 97

  20. P53-miR-191-SOX4 regulatory loop affects apoptosis in breast cancer.

    Science.gov (United States)

    Sharma, Shivani; Nagpal, Neha; Ghosh, Prahlad C; Kulshreshtha, Ritu

    2017-08-01

    miRNAs have emerged as key participants of p53 signaling pathways because they regulate or are regulated by p53. Here, we provide the first study demonstrating direct regulation of an oncogenic miRNA, miR-191-5p, by p53 and existence of a regulatory feedback loop. Using a combination of qRT-PCR, promoter-luciferase, and chromatin-immunoprecipitation assays, we show that p53 brings about down-regulation of miR-191-5p in breast cancer. miR-191-5p overexpression brought about inhibition of apoptosis in breast cancer cell lines (MCF7 and ZR-75) as demonstrated by reduction in annexin-V stained cells and caspase 3/7 activity, whereas miR-191-5p down-regulation showed the opposite. We further unveiled that SOX4 was a direct target of miR-191-5p. SOX4 overexpression was shown to increase p53 protein levels in MCF7 cells. miR-191-5p overexpression brought about down-regulation of SOX4 and thus p53 levels, suggesting the existence of a regulatory feedback loop. Breast cancer treatment by doxorubicin, an anti-cancer drug, involves induction of apoptosis by p53; we thus wanted to check whether miR-191-5p affects doxorubicin sensitivity. Interestingly, Anti-miR-191 treatment significantly decreased the IC50 of the doxorubicin drug and thus sensitized breast cancer cells to doxorubicin treatment by promoting apoptosis. Overall, this work highlights the importance of the p53-miR-191- SOX4 axis in the regulation of apoptosis and drug resistance in breast cancer and offers a preclinical proof-of-concept for use of an Anti-miR-191 and doxorubicin combination as a rational approach to pursue for better breast cancer treatment. © 2017 Sharma et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

  1. Multiplex zymography captures stage-specific activity profiles of cathepsins K, L, and S in human breast, lung, and cervical cancer.

    Science.gov (United States)

    Chen, Binbin; Platt, Manu O

    2011-07-14

    Cathepsins K, L, and S are cysteine proteases upregulated in cancer and proteolyze extracellular matrix to facilitate metastasis, but difficulty distinguishing specific cathepsin activity in complex tissue extracts confounds scientific studies and employing them for use in clinical diagnoses. Here, we have developed multiplex cathepsin zymography to profile cathepsins K, L, and S activity in 10 μg human breast, lung, and cervical tumors by exploiting unique electrophoretic mobility and renaturation properties. Frozen breast, lung, and cervix cancer tissue lysates and normal organ tissue lysates from the same human patients were obtained (28 breast tissues, 23 lung tissues, and 23 cervix tissues), minced and homogenized prior to loading for cathepsin gelatin zymography to determine enzymatic activity. Cleared bands of cathepsin activity were identified and validated in tumor extracts and detected organ- and stage-specific differences in activity. Cathepsin K was unique compared to cathepsins L and S. It was significantly higher for all cancers even at the earliest stage tested (stage I for lung and cervix (n = 6, p zymography, yielded 100% sensitivity and specificity for 20 breast tissue samples tested (10 normal; 10 tumor) in part due to the consistent absence of cathepsin K in normal breast tissue across all patients. To summarize, this sensitive assay provides quantitative outputs of cathepsins K, L, and S activities from mere micrograms of tissue and has potential use as a supplement to histological methods of clinical diagnoses of biopsied human tissue.

  2. Prognostic and functional role of subtype-specific tumor-stroma interaction in breast cancer.

    Science.gov (United States)

    Merlino, Giuseppe; Miodini, Patrizia; Callari, Maurizio; D'Aiuto, Francesca; Cappelletti, Vera; Daidone, Maria Grazia

    2017-10-01

    None of the clinically relevant gene expression signatures available for breast cancer were specifically developed to capture the influence of the microenvironment on tumor cells. Here, we attempted to build subtype-specific signatures derived from an in vitro model reproducing tumor cell modifications after interaction with activated or normal stromal cells. Gene expression signatures derived from HER2+, luminal, and basal breast cancer cell lines (treated by normal fibroblasts or cancer-associated fibroblasts conditioned media) were evaluated in clinical tumors by in silico analysis on published gene expression profiles (GEPs). Patients were classified as microenvironment-positive (μENV+ve), that is, with tumors showing molecular profiles suggesting activation by the stroma, or microenvironment-negative (μENV-ve) based on correlation of their tumors' GEP with the respective subtype-specific signature. Patients with estrogen receptor alpha (ER)+/HER2-/μENV+ve tumors were characterized by 2.5-fold higher risk of developing distant metastases (HR = 2.546; 95% CI: 1.751-3.701, P = 9.84E-07), while μENV status did not affect, or only suggested the risk of distant metastases, in women with HER2+ (HR = 1.541; 95% CI: 0.788-3.012, P = 0.206) or ER-/HER2- tumors (HR = 1.894; 95% CI: 0.938-3.824; P = 0.0747), respectively. In ER+/HER2- tumors, the μENV status remained significantly associated with metastatic progression (HR = 2.098; CI: 1.214-3.624; P = 0.00791) in multivariable analysis including size, age, and Genomic Grade Index. Validity of our in vitro model was also supported by in vitro biological endpoints such as cell growth (MTT assay) and migration/invasion (Transwell assay). In vitro-derived gene signatures tracing the bidirectional interaction with cancer activated fibroblasts are subtype-specific and add independent prognostic information to classical prognostic variables in women with ER+/HER2- tumors. © 2017 The Authors. Published

  3. Breast Cancer Methylomes Establish an Epigenomic Foundation for Metastasis

    Science.gov (United States)

    Fang, Fang; Turcan, Sevin; Rimner, Andreas; Kaufman, Andrew; Giri, Dilip; Morris, Luc G. T.; Shen, Ronglai; Seshan, Venkatraman; Mo, Qianxing; Heguy, Adriana; Baylin, Stephen B.; Ahuja, Nita; Viale, Agnes; Massague, Joan; Norton, Larry; Vahdat, Linda T.; Moynahan, Mary Ellen; Chan, Timothy A.

    2011-01-01

    Cancer-specific alterations in DNA methylation are hallmarks of human malignancies; however, the nature of the breast cancer epigenome and its effects on metastatic behavior remain obscure. To address this issue, we used genome-wide analysis to characterize the methylomes of breast cancers with diverse metastatic behavior. Groups of breast tumors were characterized by the presence or absence of coordinate hypermethylation at a large number of genes, demonstrating a breast CpG island methylator phenotype (B-CIMP). The B-CIMP provided a distinct epigenomic profile and was a strong determinant of metastatic potential. Specifically, the presence of the B-CIMP in tumors was associated with low metastatic risk and survival, and the absence of the B-CIMP was associated with high metastatic risk and death. B-CIMP loci were highly enriched for genes that make up the metastasis transcriptome. Methylation at B-CIMP genes accounted for much of the transcriptomal diversity between breast cancers of varying prognosis, indicating a fundamental epigenomic contribution to metastasis. Comparison of the loci affected by the B-CIMP with those affected by the hypermethylator phenotype in glioma and colon cancer revealed that the CIMP signature was shared by multiple human malignancies. Our data provide a unifying epigenomic framework linking breast cancers with varying outcome and transcriptomic changes underlying metastasis. These findings significantly enhance our understanding of breast cancer oncogenesis and aid the development of new prognostic biomarkers for this common malignancy. PMID:21430268

  4. Targeting ceramide metabolic pathway induces apoptosis in human breast cancer cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Vethakanraj, Helen Shiphrah; Babu, Thabraz Ahmed; Sudarsanan, Ganesh Babu; Duraisamy, Prabhu Kumar; Ashok Kumar, Sekar, E-mail: sekarashok@gmail.com

    2015-08-28

    The sphingolipid ceramide is a pro apoptotic molecule of ceramide metabolic pathway and is hydrolyzed to proliferative metabolite, sphingosine 1 phosphate by the action of acid ceramidase. Being upregulated in the tumors of breast, acid ceramidase acts as a potential target for breast cancer therapy. We aimed at targeting this enzyme with a small molecule acid ceramidase inhibitor, Ceranib 2 in human breast cancer cell lines MCF 7 and MDA MB 231. Ceranib 2 effectively inhibited the growth of both the cell lines in dose and time dependant manner. Morphological apoptotic hallmarks such as chromatin condensation, fragmented chromatin were observed in AO/EtBr staining. Moreover, ladder pattern of fragmented DNA observed in DNA gel electrophoresis proved the apoptotic activity of Ceranib 2 in breast cancer cell lines. The apoptotic events were associated with significant increase in the expression of pro-apoptotic genes (Bad, Bax and Bid) and down regulation of anti-apoptotic gene (Bcl 2). Interestingly, increase in sub G1 population of cell cycle phase analysis and elevated Annexin V positive cells after Ceranib 2 treatment substantiated its apoptotic activity in MCF 7 and MDA MB 231 cell lines. Thus, we report Ceranib 2 as a potent therapeutic agent against both ER{sup +} and ER{sup −} breast cancer cell lines. - Highlights: • Acid Ceramidase inhibitor, Ceranib 2 induced apoptosis in Breast cancer cell lines (MCF 7 and MDA MB 231 cell lines). • Apoptosis is mediated by DNA fragmentation and cell cycle arrest. • Ceranib 2 upregulated the expression of pro-apoptotic genes and down regulated anti-apoptotic gene expression. • More potent compared to the standard drug Tamoxifen.

  5. Targeting ceramide metabolic pathway induces apoptosis in human breast cancer cell lines

    International Nuclear Information System (INIS)

    Vethakanraj, Helen Shiphrah; Babu, Thabraz Ahmed; Sudarsanan, Ganesh Babu; Duraisamy, Prabhu Kumar; Ashok Kumar, Sekar

    2015-01-01

    The sphingolipid ceramide is a pro apoptotic molecule of ceramide metabolic pathway and is hydrolyzed to proliferative metabolite, sphingosine 1 phosphate by the action of acid ceramidase. Being upregulated in the tumors of breast, acid ceramidase acts as a potential target for breast cancer therapy. We aimed at targeting this enzyme with a small molecule acid ceramidase inhibitor, Ceranib 2 in human breast cancer cell lines MCF 7 and MDA MB 231. Ceranib 2 effectively inhibited the growth of both the cell lines in dose and time dependant manner. Morphological apoptotic hallmarks such as chromatin condensation, fragmented chromatin were observed in AO/EtBr staining. Moreover, ladder pattern of fragmented DNA observed in DNA gel electrophoresis proved the apoptotic activity of Ceranib 2 in breast cancer cell lines. The apoptotic events were associated with significant increase in the expression of pro-apoptotic genes (Bad, Bax and Bid) and down regulation of anti-apoptotic gene (Bcl 2). Interestingly, increase in sub G1 population of cell cycle phase analysis and elevated Annexin V positive cells after Ceranib 2 treatment substantiated its apoptotic activity in MCF 7 and MDA MB 231 cell lines. Thus, we report Ceranib 2 as a potent therapeutic agent against both ER + and ER − breast cancer cell lines. - Highlights: • Acid Ceramidase inhibitor, Ceranib 2 induced apoptosis in Breast cancer cell lines (MCF 7 and MDA MB 231 cell lines). • Apoptosis is mediated by DNA fragmentation and cell cycle arrest. • Ceranib 2 upregulated the expression of pro-apoptotic genes and down regulated anti-apoptotic gene expression. • More potent compared to the standard drug Tamoxifen

  6. BCL-2 family protein, BAD is down-regulated in breast cancer and inhibits cell invasion.

    Science.gov (United States)

    Cekanova, Maria; Fernando, Romaine I; Siriwardhana, Nalin; Sukhthankar, Mugdha; De la Parra, Columba; Woraratphoka, Jirayus; Malone, Christine; Ström, Anders; Baek, Seung J; Wade, Paul A; Saxton, Arnold M; Donnell, Robert M; Pestell, Richard G; Dharmawardhane, Suranganie; Wimalasena, Jay

    2015-02-01

    We have previously demonstrated that the anti-apoptotic protein BAD is expressed in normal human breast tissue and shown that BAD inhibits expression of cyclin D1 to delay cell-cycle progression in breast cancer cells. Herein, expression of proteins in breast tissues was studied by immunohistochemistry and results were analyzed statistically to obtain semi-quantitative data. Biochemical and functional changes in BAD-overexpressing MCF7 breast cancer cells were evaluated using PCR, reporter assays, western blotting, ELISA and extracellular matrix invasion assays. Compared to normal tissues, Grade II breast cancers expressed low total/phosphorylated forms of BAD in both cytoplasmic and nuclear compartments. BAD overexpression decreased the expression of β-catenin, Sp1, and phosphorylation of STATs. BAD inhibited Ras/MEK/ERK and JNK signaling pathways, without affecting the p38 signaling pathway. Expression of the metastasis-related proteins, MMP10, VEGF, SNAIL, CXCR4, E-cadherin and TlMP2 was regulated by BAD with concomitant inhibition of extracellular matrix invasion. Inhibition of BAD by siRNA increased invasion and Akt/p-Akt levels. Clinical data and the results herein suggest that in addition to the effect on apoptosis, BAD conveys anti-metastatic effects and is a valuable prognostic marker in breast cancer. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Outcome of breast cancer screening in Denmark

    DEFF Research Database (Denmark)

    Lynge, Elsebeth; Bak, Martin; von Euler-Chelpin, My

    2017-01-01

    were node negative and 40% ≤10 mm. False-positive rate was around 2%; higher for North Denmark Region than for the rest of Denmark. Three out of 10 breast cancers in screened women were diagnosed as interval cancers. Conclusions: High coverage by examination and low interval cancer rate are required...... for screening to decrease breast cancer mortality. Two pioneer local screening programs starting in the 1990s were followed by a decrease in breast cancer mortality of 22-25%. Coverage by examination and interval cancer rate of the national program were on the favorable side of values from the pioneer programs...... calculated coverage by examination; participation after invitation; detection-, interval cancer- and false-positive rates; cancer characteristics; sensitivity and specificity, for Denmark and for the five regions. Results: At the national level coverage by examination remained at 75-77%; lower in the Capital...

  8. Mechanism and preclinical prevention of increased breast cancer risk caused by pregnancy.

    Science.gov (United States)

    Haricharan, Svasti; Dong, Jie; Hein, Sarah; Reddy, Jay P; Du, Zhijun; Toneff, Michael; Holloway, Kimberly; Hilsenbeck, Susan G; Huang, Shixia; Atkinson, Rachel; Woodward, Wendy; Jindal, Sonali; Borges, Virginia F; Gutierrez, Carolina; Zhang, Hong; Schedin, Pepper J; Osborne, C Kent; Tweardy, David J; Li, Yi

    2013-12-31

    While a first pregnancy before age 22 lowers breast cancer risk, a pregnancy after age 35 significantly increases life-long breast cancer risk. Pregnancy causes several changes to the normal breast that raise barriers to transformation, but how pregnancy can also increase cancer risk remains unclear. We show in mice that pregnancy has different effects on the few early lesions that have already developed in the otherwise normal breast-it causes apoptosis evasion and accelerated progression to cancer. The apoptosis evasion is due to the normally tightly controlled STAT5 signaling going astray-these precancerous cells activate STAT5 in response to pregnancy/lactation hormones and maintain STAT5 activation even during involution, thus preventing the apoptosis normally initiated by oncoprotein and involution. Short-term anti-STAT5 treatment of lactation-completed mice bearing early lesions eliminates the increased risk after a pregnancy. This chemoprevention strategy has important implications for preventing increased human breast cancer risk caused by pregnancy. DOI: http://dx.doi.org/10.7554/eLife.00996.001.

  9. Acceleration of leukocytes' epigenetic age as an early tumor and sex-specific marker of breast and colorectal cancer.

    Science.gov (United States)

    Durso, Danielle Fernandes; Bacalini, Maria Giulia; Sala, Claudia; Pirazzini, Chiara; Marasco, Elena; Bonafé, Massimiliano; do Valle, Ítalo Faria; Gentilini, Davide; Castellani, Gastone; Faria, Ana Maria Caetano; Franceschi, Claudio; Garagnani, Paolo; Nardini, Christine

    2017-04-04

    Changes in blood epigenetic age have been associated with several pathological conditions and have recently been described to anticipate cancer development. In this work, we analyze a publicly available leukocytes methylation dataset to evaluate the relation between DNA methylation age and the prospective development of specific types of cancer. We calculated DNA methylation age acceleration using five state-of-the-art estimators (three multi-site: Horvath, Hannum, Weidner; and two CpG specific: ELOV2 and FHL2) in a cohort including 845 subjects from the EPIC-Italy project and we compared 424 samples that remained cancer-free over the approximately ten years of follow-up with 235 and 166 subjects who developed breast and colorectal cancer, respectively. We show that the epigenetic age estimated from blood DNA methylation data is statistically significantly associated to future breast and male colorectal cancer development. These results are corroborated by survival analysis that shows significant association between age acceleration and cancer incidence suggesting that the chance of developing age-related diseases may be predicted by circulating epigenetic markers, with a dependence upon tumor type, sex and age estimator. These are encouraging results towards the non-invasive and perspective usage of epigenetic biomarkers.

  10. Exploring the breast cancer patient journey: do breast cancer survivors need menopause management support?

    Science.gov (United States)

    Tanna, Nuttan; Buijs, Helene; Pitkin, Joan

    2011-12-01

    Breast cancer survivors can be expected to suffer from menopause symptoms with estrogen deprivation due to cancer treatments, in addition to natural menopause-related estrogen loss. To gain an understanding of what support breast cancer patients have when they suffer from menopausal symptoms, and utilize findings to further inform National Health Service (NHS) care provision for breast cancer survivors. Qualitative study with focus group sessions targeting Caucasian and Asian women with breast cancer. Patient stories, with women describing their breast cancer journey and speaking about support received for any menopausal symptoms. Thematic data analysis of transcription. Breast cancer patients were not sure if they had menopausal symptoms or whether this was due to their breast cancer condition or treatment. Patients had an attitude of acceptance of menopausal symptoms and reported trying to cope with these by themselves. This research identifies a need for more information that is culturally sensitive on managing menopause symptoms, both as side-effects of breast cancer treatments as well as for affect on quality of life during the survivorship phase. Our work also gives insight into cultural remedies used for hot flushes by Asian patients, which they consider as 'cooling' foods. Breast cancer patients want to know whether side-effects of cancer treatment persist long term and how these can be managed. There is a need for improved patient support within any new NHS service models that are developed along breast cancer patient pathways, and inclusion of personalized advice for menopause symptoms.

  11. Hypnosis for Hot Flashes and Associated Symptomsin Women with Breast Cancer.

    Science.gov (United States)

    Roberts, R Lynae; Na, Hyeji; Yek, Ming Hwei; Elkins, Gary

    2017-10-01

    Women with breast cancer experience a host of physical and psychological symptoms, including hot flashes, sleep difficulties, anxiety, and depression. Therefore, treatment for women with breast cancer should target these symptoms and be individualized to patients' specific presentations. The current article reviews the common symptoms associated with breast cancer in women, then examines clinical hypnosis as a treatment for addressing these symptoms and improving the quality of life of women with breast cancer. Clinical hypnosis is an effective, nonpharmaceutical treatment for hot flashes and addressing many symptoms typically experienced by breast cancer patients. A case example is provided to illustrate the use of clinical hypnosis for the treatment of hot flashes with a patient with breast cancer.

  12. The Effect of Simvastatin on Breast Cancer Cell Growth in Women With Stage I-II Breast Cancer

    Science.gov (United States)

    2018-03-02

    Invasive Breast Carcinoma; Stage I Breast Cancer AJCC v7; Stage IA Breast Cancer AJCC v7; Stage IB Breast Cancer AJCC v7; Stage II Breast Cancer AJCC v6 and v7; Stage IIA Breast Cancer AJCC v6 and v7; Stage IIB Breast Cancer AJCC v6 and v7

  13. Nanomedicine applications in the treatment of breast cancer: current state of the art

    Directory of Open Access Journals (Sweden)

    Wu D

    2017-08-01

    Full Text Available Di Wu, Mengjie Si, Hui-Yi Xue, Ho-Lun Wong Department of Pharmaceutical Sciences, Temple University School of Pharmacy, Philadelphia, PA, USA Abstract: Breast cancer is the most common malignant disease in women worldwide, but the current drug therapy is far from optimal as indicated by the high death rate of breast cancer patients. Nanomedicine is a promising alternative for breast cancer treatment. Nanomedicine products such as Doxil® and Abraxane® have already been extensively used for breast cancer adjuvant therapy with favorable clinical outcomes. However, these products were originally designed for generic anticancer purpose and not specifically for breast cancer treatment. With better understanding of the molecular biology of breast cancer, a number of novel promising nanotherapeutic strategies and devices have been developed in recent years. In this review, we will first give an overview of the current breast cancer treatment and the updated status of nanomedicine use in clinical setting, then discuss the latest important trends in designing breast cancer nanomedicine, including passive and active cancer cell targeting, breast cancer stem cell targeting, tumor microenvironment-based nanotherapy and combination nanotherapy of drug-resistant breast cancer. Researchers may get insight from these strategies to design and develop nanomedicine that is more tailored for breast cancer to achieve further improvements in cancer specificity, antitumorigenic effect, antimetastasis effect and drug resistance reversal effect. Keywords: nanomedicine, breast cancer, targeted delivery, drug therapy, drug resistance, tumor microenvironment 

  14. Association of Epstein Barr virus infection (EBV with breast cancer in rural Indian women.

    Directory of Open Access Journals (Sweden)

    Deepti Joshi

    Full Text Available INTRODUCTION: Breast cancer is the most common malignancy affecting females worldwide but conventional risk factors are able to explain only a small proportion of these cases. A possible viral etiology for breast cancer has been proposed and Epstein-Barr Virus (EBV is a widely researched candidate virus. The aim of the present study, first one of its kind from India, was to determine if there is a greater association of EBV infection with breast cancer patients as compared to patients with benign breast diseases. METHODS: We looked for expression of Epstein-Barr Virus Nuclear Antigen-1 (EBNA-1 in breast cancer tissue specimens by employing immunohistochemistry (IHC. We also measured levels of anti-EBNA-1 Immunoglobulin (IgG antibodies in stored sera of these patients using commercial Enzyme linked Immunosorbent Assay (ELISA kit. Patients with benign breast diseases were used as a comparison group for both immunohistochemical and serological analysis. RESULTS: 58 cases of malignant breast disease and 63 of benign breast disease (controls were included in the study. Using manufacturer determined cut-off of 3 IU/ml, 50/55 tested (90.9% cases and 27/33 tested (81.8% controls were seropositive for anti-EBNA-1 IgG. Mean antibody levels were significantly higher for cases (54.22 IU/ml as compared to controls (18.68 IU/ml. IHC for EBNA-1 was positive in 28/51 cases (54.9%. No IHC positivity was noted in the tested 30 controls. Our results show that EBNA-1 expression is seen in a significant proportion of breast cancer tissue specimens from rural India and as compared to patients with benign breast diseases these patients also have a higher immunological response against EBNA-1.

  15. Identification of differentially expressed microRNAs in human male breast cancer

    Directory of Open Access Journals (Sweden)

    Schipper Elisa

    2010-03-01

    Full Text Available Abstract Background The discovery of small non-coding RNAs and the subsequent analysis of microRNA expression patterns in human cancer specimens have provided completely new insights into cancer biology. Genetic and epigenetic data indicate oncogenic or tumor suppressor function of these pleiotropic regulators. Therefore, many studies analyzed the expression and function of microRNA in human breast cancer, the most frequent malignancy in females. However, nothing is known so far about microRNA expression in male breast cancer, accounting for approximately 1% of all breast cancer cases. Methods The expression of 319 microRNAs was analyzed in 9 primary human male breast tumors and in epithelial cells from 15 male gynecomastia specimens using fluorescence-labeled bead technology. For identification of differentially expressed microRNAs data were analyzed by cluster analysis and selected statistical methods. Expression levels were validated for the most up- or down-regulated microRNAs in this training cohort using real-time PCR methodology as well as in an independent test cohort comprising 12 cases of human male breast cancer. Results Unsupervised cluster analysis separated very well male breast cancer samples and control specimens according to their microRNA expression pattern indicating cancer-specific alterations of microRNA expression in human male breast cancer. miR-21, miR519d, miR-183, miR-197, and miR-493-5p were identified as most prominently up-regulated, miR-145 and miR-497 as most prominently down-regulated in male breast cancer. Conclusions Male breast cancer displays several differentially expressed microRNAs. Not all of them are shared with breast cancer biopsies from female patients indicating male breast cancer specific alterations of microRNA expression.

  16. Breast cancer services in Vietnam: a scoping review.

    Science.gov (United States)

    Jenkins, Chris; Minh, Luu Ngoc; Anh, Tran Tuan; Ngan, Tran Thu; Tuan, Ngo Tri; Giang, Kim Bao; Hoat, Luu Ngoc; Lohfeld, Lynne; Donnelly, Michael; Van Minh, Hoang; Murray, Liam

    2018-01-01

    Breast cancer incidence has been increasing consistently in Vietnam. Thus far, there have been no analytical reviews of research produced within this area. We sought to analyse the nature andextent of empirical studies about breast cancer in Vietnam, identifying areas for future research and systemsstrengthening. We undertook a scoping study using a five-stage framework to review published and grey literature in English and Vietnamese on breast cancer detection, diagnosis and treatment. We focused specifically on research discussing the health system and service provision. Our results show that breast cancer screening is limited, with no permanent or integrated national screening activities. There is a lack of information on screening processes and on the integration of screening services with other areas of the health system. Treatment is largely centralised, and across all services there is a lack of evaluation and data collection that would be informative for recommendations seeking to improve accessibility and quality of breast cancer services. This paper is the first scoping review of breast cancer services in Vietnam. It outlines areas for future focus for policy makers and researchers with the objective of strengthening service provision to women with breast cancer across the country while also providing a methodological example for how to conduct a collaborative scoping review.

  17. EHMT2 is a metastasis regulator in breast cancer.

    Science.gov (United States)

    Kim, Kwangho; Son, Mi-Young; Jung, Cho-Rok; Kim, Dae-Soo; Cho, Hyun-Soo

    2018-02-05

    Various modes of epigenetic regulation of breast cancer proliferation and metastasis have been investigated, but epigenetic mechanisms involved in breast cancer metastasis remain elusive. Thus, in this study, EHMT2 (a histone methyltransferase) was determined to be significantly overexpressed in breast cancer tissues and in Oncomine data. In addition, knockdown of EHMT2 reduced cell migration/invasion and regulated the expression of EMT-related markers (E-cadherin, Claudin 1, and Vimentin). Furthermore, treatment with BIX-01294, a specific inhibitor of EHMT2, affected migration/invasion in MDA-MB-231 cells. Therefore, our findings demonstrate functions of EHMT2 in breast cancer metastasis and suggest that targeting EHMT2 may be an effective therapeutic strategy for preventing breast cancer metastasis. Copyright © 2018 Elsevier Inc. All rights reserved.

  18. Epidemiology, Incidence and Mortality of Breast Cancer in Asia.

    Science.gov (United States)

    Ghoncheh, Mahshid; Momenimovahed, Zohre; Salehiniya, Hamid

    2016-01-01

    Breast cancer is the most common malignancy in women around the world. Information on the incidence and mortality of breast cancer is essential for planning health measures. This study aimed to investigate the incidence and mortality of breast cancer in the world using age-specific incidence and mortality rates for the year 2012 acquired from the global cancer project (GLOBOCAN 2012) as well as data about incidence and mortality of the cancer based on national reports. It was estimated that 1,671,149 new cases of breast cancer were identified and 521,907 cases of deaths due to breast cancer occurred in the world in 2012. According to GLOBOCAN, it is the most common cancer in women, accounting for 25.1% of all cancers. Breast cancer incidence in developed countries is higher, while relative mortality is greatest in less developed countries. Education of women is suggested in all countries for early detection and treatment. Plans for the control and prevention of this cancer must be a high priority for health policy makers; also, it is necessary to increase awareness of risk factors and early detection in less developed countries.

  19. Anti-Cancer Effect of Angelica Sinensis on Women’s Reproductive Cancer

    Directory of Open Access Journals (Sweden)

    Hong-Hong Zhu

    2012-06-01

    Full Text Available Objective: Danggui, the root of Angelica Sinensis, has traditionally been used for the treatment of women’s reproductive disorders in China for thousands of years. This study was to determine whether Danggui have potential anti-cancer effect on women’s cancer and its potential mechanism. Methods: Danggui was extracted by ethanol. The Cell Titer 96® Aqueous Non-Radioactive Cell Proliferation Assay was used to compare the effects of Danggui on human breast (MCF-7 and 7368 and cervical (CaSki and SiHa cancer cells with its effects on normal fibroblasts (HTB-125. A revised Ames test was used to test for antimutagenicity. The standard strains of Salmonella typhimarium (TA 100 and 102 were used in the test. Methyl methane sulfonate (MMS and UV light were used as positive mutagen controls and ethanol and double distilled water (DDW as controls. The SAS statistical software was used to analyze the data. Results: Danggui was found to be much more toxic to all cancer cell lines tested than to normal fibroblasts. There was a significant negative dose-effect relationship between Danggui and cancer cell viability. Average viability of MCF-7 was 69.5%, 18.4%, 5.7%, 5.7%, and 5.0% of control for Danggui doses 0.07, 0.14, 0.21, 0.32, and 0.64 ug/ul, respectively, with a Ptrend < 0.0001. Half maximal inhibitory dose (ID50 of Danggui for cancer cell lines MCF-7, CaSki, SiHa and CRL-7368 was 0.10, 0.09, 0.10 and 0.07 ug/ul, Functional Foods in Health and Disease 2012, 2(6:242-250respectively. For the normal fibroblasts, ID50 was 0.58 ug/ul. At a dose of 0.32 ug/ul, Danggui killed over 90% of the cells in each cancer cell line, but at the same dose, only 12.3 % of the normal HTB-125 cells were killed. Revertants per plate of TA 100 decreased with the introduction of increasing doses of Danggui extracts with a Ptrend < 0.0001 when UV light was used as a mutagen. There was no difference in revertants per plate between ethanol and DDW control groups. Conclusions

  20. Optimization of anti-cancer drugs and a targeting molecule on multifunctional gold nanoparticles

    International Nuclear Information System (INIS)

    Rizk, Nahla; Christoforou, Nicolas; Lee, Sungmun

    2016-01-01

    Breast cancer is the most common and deadly cancer among women worldwide. Currently, nanotechnology-based drug delivery systems are useful for cancer treatment; however, strategic planning is critical in order to enhance the anti-cancer properties and reduce the side effects of cancer therapy. Here, we designed multifunctional gold nanoparticles (AuNPs) conjugated with two anti-cancer drugs, TGF-β1 antibody and methotrexate, and a cancer-targeting molecule, folic acid. First, optimum size and shape of AuNPs was selected by the highest uptake of AuNPs by MDA-MB-231, a metastatic human breast cancer cell line. It was 100 nm spherical AuNPs (S-AuNPs) that were used for further studies. A fixed amount (900 μl) of S-AuNP (3.8 × 10"8 particles/ml) was conjugated with folic acid-BSA or methotrexate-BSA. Methotrexate on S-AuNP induced cellular toxicity and the optimum amount of methotrexate-BSA (2.83 mM) was 500 μl. Uptake of S-AuNPs was enhanced by folate conjugation that binds to folate receptors overexpressed by MDA-MB-231 and the optimum uptake was at 500 μl of folic acid-BSA (2.83 mM). TGF-β1 antibody on S-AuNP reduced extracellular TGF-β1 of cancer cells by 30%. Due to their efficacy and tunable properties, we anticipate numerous clinical applications of multifunctional gold nanospheres in treating breast cancer. (paper)

  1. Optimization of anti-cancer drugs and a targeting molecule on multifunctional gold nanoparticles

    Science.gov (United States)

    Rizk, Nahla; Christoforou, Nicolas; Lee, Sungmun

    2016-05-01

    Breast cancer is the most common and deadly cancer among women worldwide. Currently, nanotechnology-based drug delivery systems are useful for cancer treatment; however, strategic planning is critical in order to enhance the anti-cancer properties and reduce the side effects of cancer therapy. Here, we designed multifunctional gold nanoparticles (AuNPs) conjugated with two anti-cancer drugs, TGF-β1 antibody and methotrexate, and a cancer-targeting molecule, folic acid. First, optimum size and shape of AuNPs was selected by the highest uptake of AuNPs by MDA-MB-231, a metastatic human breast cancer cell line. It was 100 nm spherical AuNPs (S-AuNPs) that were used for further studies. A fixed amount (900 μl) of S-AuNP (3.8 × 108 particles/ml) was conjugated with folic acid-BSA or methotrexate-BSA. Methotrexate on S-AuNP induced cellular toxicity and the optimum amount of methotrexate-BSA (2.83 mM) was 500 μl. Uptake of S-AuNPs was enhanced by folate conjugation that binds to folate receptors overexpressed by MDA-MB-231 and the optimum uptake was at 500 μl of folic acid-BSA (2.83 mM). TGF-β1 antibody on S-AuNP reduced extracellular TGF-β1 of cancer cells by 30%. Due to their efficacy and tunable properties, we anticipate numerous clinical applications of multifunctional gold nanospheres in treating breast cancer.

  2. Pre-diagnostic alcohol consumption and breast cancer recurrence and mortality

    DEFF Research Database (Denmark)

    Holm, Marianne; Olsen, Anja; Christensen, Jane

    2013-01-01

    The association between pre-diagnostic alcohol consumption and breast cancer recurrence and breast cancer specific mortality was investigated in 1,052 women diagnosed with early breast cancer in a prospective cohort of 29,875 women. Known clinical, lifestyle and socioeconomic risk factors were...... evaluated and adjusted for in multivariate analysis. We found a modest but significant association between pre-diagnostic alcohol consumption and breast cancer recurrence with a median follow-up of six years after date of diagnosis, both when using baseline measures of alcohol intake (HR, 1.65; 95% CI, 1...

  3. Ki67 and proliferation in breast cancer.

    Science.gov (United States)

    Pathmanathan, Nirmala; Balleine, Rosemary L

    2013-06-01

    New approaches to the prognostic assessment of breast cancer have come from molecular profiling studies. A major feature of this work has been to emphasise the importance of cancer cell proliferation as a key discriminative indicator of recurrence risk for oestrogen receptor positive breast cancer in particular. Mitotic count scoring, as a component of histopathological grade, has long formed part of a routine evaluation of breast cancer biology. However, there is an increasingly compelling case to include a specific proliferation score in breast cancer pathology reports based on expression of the cell cycle regulated protein Ki67. Immunohistochemical staining for Ki67 is a widely available and economical test with good tolerance of pre-analytical variations and staining conditions. However, there is currently no evidence based protocol established to derive a reliable and informative Ki67 score for routine clinical use. In this circumstance, pathologists must establish a standardised framework for scoring Ki67 and communicating results to a multidisciplinary team.

  4. NUCKS overexpression in breast cancer

    Directory of Open Access Journals (Sweden)

    Kittas Christos

    2009-08-01

    Full Text Available Abstract Background NUCKS (Nuclear, Casein Kinase and Cyclin-dependent Kinase Substrate is a nuclear, DNA-binding and highly phosphorylated protein. A number of reports show that NUCKS is highly expressed on the level of mRNA in several human cancers, including breast cancer. In this work, NUCKS expression on both RNA and protein levels was studied in breast tissue biopsies consisted of invasive carcinomas, intraductal proliferative lesions, benign epithelial proliferations and fibroadenomas, as well as in primary cultures derived from the above biopsies. Specifically, in order to evaluate the level of NUCKS protein in correlation with the histopathological features of breast disease, immunohistochemistry was employed on paraffin sections of breast biopsies of the above types. In addition, NUCKS expression was studied by means of Reverse Transcription PCR (RT-PCR, real-time PCR (qRT-PCR and Western immunoblot analyses in the primary cell cultures developed from the same biopsies. Results The immunohistochemical Results showed intense NUCKS staining mostly in grade I and II breast carcinomas compared to normal tissues. Furthermore, NUCKS was moderate expressed in benign epithelial proliferations, such as adenosis and sclerosing adenosis, and highly expressed in intraductal lesions, specifically in ductal carcinomas in situ (DCIS. It is worth noting that all the fibroadenoma tissues examined were negative for NUCKS staining. RT-PCR and qRT-PCR showed an increase of NUCKS expression in cells derived from primary cultures of proliferative lesions and cancerous tissues compared to the ones derived from normal breast tissues and fibroadenomas. This increase was also confirmed by Western immunoblot analysis. Although NUCKS is a cell cycle related protein, its expression does not correlate with Ki67 expression, neither in tissue sections nor in primary cell cultures. Conclusion The results show overexpression of the NUCKS protein in a number of non

  5. The Role of RB in the Therapeutic Response of Breast Cancer

    National Research Council Canada - National Science Library

    Bosco, Emily E

    2005-01-01

    The retinoblastoma tumor suppressor protein (RB) participates in the growth regulation of breast cancer cells by controlling G-S phase progression and mediating cell cycle arrest in response to anti-mitogenic signaling...

  6. Breast cancer statistics, 2011.

    Science.gov (United States)

    DeSantis, Carol; Siegel, Rebecca; Bandi, Priti; Jemal, Ahmedin

    2011-01-01

    In this article, the American Cancer Society provides an overview of female breast cancer statistics in the United States, including trends in incidence, mortality, survival, and screening. Approximately 230,480 new cases of invasive breast cancer and 39,520 breast cancer deaths are expected to occur among US women in 2011. Breast cancer incidence rates were stable among all racial/ethnic groups from 2004 to 2008. Breast cancer death rates have been declining since the early 1990s for all women except American Indians/Alaska Natives, among whom rates have remained stable. Disparities in breast cancer death rates are evident by state, socioeconomic status, and race/ethnicity. While significant declines in mortality rates were observed for 36 states and the District of Columbia over the past 10 years, rates for 14 states remained level. Analyses by county-level poverty rates showed that the decrease in mortality rates began later and was slower among women residing in poor areas. As a result, the highest breast cancer death rates shifted from the affluent areas to the poor areas in the early 1990s. Screening rates continue to be lower in poor women compared with non-poor women, despite much progress in increasing mammography utilization. In 2008, 51.4% of poor women had undergone a screening mammogram in the past 2 years compared with 72.8% of non-poor women. Encouraging patients aged 40 years and older to have annual mammography and a clinical breast examination is the single most important step that clinicians can take to reduce suffering and death from breast cancer. Clinicians should also ensure that patients at high risk of breast cancer are identified and offered appropriate screening and follow-up. Continued progress in the control of breast cancer will require sustained and increased efforts to provide high-quality screening, diagnosis, and treatment to all segments of the population. Copyright © 2011 American Cancer Society, Inc.

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

    Directory of Open Access Journals (Sweden)

    Jérôme Lacombe

    2014-01-01

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

  8. Combination therapies for the treatment of HER2-positive breast cancer: current and future prospects.

    Science.gov (United States)

    Brandão, Mariana; Pondé, Noam F; Poggio, Francesca; Kotecki, Nuria; Salis, Mauren; Lambertini, Matteo; de Azambuja, Evandro

    2018-05-24

    HER2-positive disease is an aggressive subtype of breast cancer that has been revolutionized by anti-HER2 directed therapies. Multiple drugs have been developed and are currently in clinical use, including trastuzumab, lapatinib, pertuzumab, T-DM1, and neratinib, alone or combined in 'dual HER2-blockade' regimens. Areas covered: A comprehensive literature review was performed regarding the current state and the future of combination regimens containing anti-HER2 agents, focusing on their efficacy, toxicity, and cost-effectiveness. Expert commentary: The combination of trastuzumab/pertuzumab is approved in all disease settings, while trastuzumab/neratinib is approved in the adjuvant setting and trastuzumab/lapatinib in metastatic disease. Meanwhile, as breast cancer biology and resistance mechanisms become clearer, combinations with drugs like PI3K/Akt/mTOR inhibitors, CDK4/6 inhibitors, anti-PD(L)1 antibodies, endocrine therapy, and new anti-HER2 agents (panHER and HER2 tyrosine kinase inhibitors, bispecific antibodies, anti-HER3 antibodies, and antibody-drug conjugates) are being extensively tested in clinical trials. More specific strategies for the 'triple-positive' (estrogen receptor-positive/HER2-positive) disease are also being explored. However, there is an urgent need for the development of predictive biomarkers for a better tailoring of anti-HER2 directed therapy. This is the only way to further improve clinical outcomes and quality of life and to decrease costs and toxicities of unnecessary treatments.

  9. Breast Cancer (For Kids)

    Science.gov (United States)

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

  10. Body mass index and survival after breast cancer diagnosis in Japanese women

    International Nuclear Information System (INIS)

    Kawai, Masaaki; Minami, Yuko; Nishino, Yoshikazu; Fukamachi, Kayoko; Ohuchi, Noriaki; Kakugawa, Yoichiro

    2012-01-01

    Body mass index (BMI) may be an important factor affecting breast cancer outcome. Studies conducted mainly in Western countries have reported a relationship between higher BMI and a higher risk of all-cause death or breast cancer-specific death among women with breast cancer, but only a few studies have been reported in Japan so far. In the present prospective study, we investigated the associations between BMI and the risk of all-cause and breast cancer-specific death among breast cancer patients overall and by menopausal status and hormone receptor status. The study included 653 breast cancer patients admitted to a single hospital in Japan, between 1997 and 2005. BMI was assessed using a self-administered questionnaire. The patients were completely followed up until December, 2008. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated according to quartile points of BMI categories, respectively: <21.2, ≥21.2 to <23.3 (reference), ≥23.3 to <25.8 and ≥25.8 kg/m 2 . During the follow-up period, 136 all-cause and 108 breast cancer-specific deaths were observed. After adjustment for clinical and confounding factors, higher BMI was associated with an increased risk of all-cause death (HR = 2.61; 95% CI: 1.01–6.78 for BMI ≥25.8 vs. ≥21.2 to <23.3 kg/m 2 ) among premenopausal patients. According to hormonal receptor status, BMI ≥25.8 kg/m 2 was associated with breast cancer-specific death (HR = 4.95; 95% CI: 1.05–23.35) and BMI <21.2 kg/m 2 was associated with all-cause (HR = 2.91; 95% CI: 1.09–7.77) and breast cancer-specific death (HR = 7.23; 95% CI: 1.57–33.34) among patients with ER + or PgR + tumors. Analysis by hormonal receptor status also showed a positive association between BMI and mortality risk among patients with ER + or PgR + tumors and with BMI ≥21.2 kg/m 2 (p for trend: 0.020 and 0.031 for all-cause and breast cancer-specific death, respectively). Our results suggest that both higher BMI and lower BMI are associated

  11. Targeted drugs and Psycho-oncological intervention for breast cancer patients.

    Science.gov (United States)

    D'Abramo, Flavio; Goerling, Ute; Guastadisegni, Cecilia

    2016-04-01

    Personalized medicine is a new field based on molecular biology and genomics in which targeted tumor therapies are administered to patients. Psycho-oncology is a complementary approach that considers social and psychological aspects of patients as part of the treatments for cancer patients. The aim of this mini-review is to weigh clinical benefits for breast cancer patients of both treatments and possibly enhance benefits by modulating the use of both interventions. We have compared and evaluated on the one hand the use of anti Vascular Endothelial Growth Factor and, on the other hand, psycho-oncological interventions in metastatic and non-metastatic breast cancer patients.Both treatments did not increase survival of metastatic breast cancer patients, while in a selected study psycho-oncological interventions extended lifespan of non-metastatic breast cancer patients and ameliorate psychological and social factors of metastatic breast cancer patients. Because the two approaches address completely different aspects of cancer patients, if the comparison is limited to the extension of survival, the value of these two treatments cannot be assessed and compared.It is likely that by comparing patients reported outcomes, possibly by using standardized Quality of Life questionnaires, both patients and health care providers can weigh the benefits of the two treatments. It is therefore important to evaluate the use of cancer patients' quality of life measures as a mean to improve their experiences about life and treatment, and possibly to extend their survival.

  12. Who's talking about breast cancer? Analysis of daily breast cancer posts on the internet.

    Science.gov (United States)

    Quinn, Edel M; Corrigan, Mark A; McHugh, Seamus M; Murphy, David; O'Mullane, John; Hill, Arnold D; Redmond, Henry Paul

    2013-02-01

    Breast cancer is the cancer most commonly searched for on the internet. Our aim was to assess daily new breast cancer related posting on the internet. We analyzed numbers of new daily posts for common cancers for one month and subsequently analyzed content of 1426 breast cancer related posts. We also assessed use of online discussion forums for breast cancer related dialogue. Breast related topics had significantly more posts per day compared to others (mean 66.7, p Anonymous posts were common (55%) and less likely to be accurate (p internet has become a primary forum within which health information, particularly relating to breast cancer, is both sought and shared. Increasingly information is provided by patients themselves. Copyright © 2012 Elsevier Ltd. All rights reserved.

  13. Identification of novel genetic markers of breast cancer survival

    NARCIS (Netherlands)

    Q. Guo (Qi); M.K. Schmidt (Marjanka); P. Kraft (Peter); S. Canisius (Sander); C. Chen (Constance); S. Khan (Sofia); J.P. Tyrer (Jonathan); M.K. Bolla (Manjeet); Q. Wang (Qing); J. Dennis (Joe); K. Michailidou (Kyriaki); M. Lush (Michael); S. Kar (Siddhartha); J. Beesley (Jonathan); A.M. Dunning (Alison); M. Shah (Mitul); K. Czene (Kamila); H. Darabi (Hatef); M. Eriksson (Mikael); D. Lambrechts (Diether); C. Weltens (Caroline); K. Leunen; S.E. Bojesen (Stig); B.G. Nordestgaard (Børge); S.F. Nielsen (Sune); H. Flyger (Henrik); J. Chang-Claude (Jenny); A. Rudolph (Anja); P. Seibold (Petra); D. Flesch-Janys (Dieter); C. Blomqvist (Carl); K. Aittomäki (Kristiina); R. Fagerholm (Rainer); T.A. Muranen (Taru); F.J. Couch (Fergus); J.E. Olson (Janet); C. Vachon (Celine); I.L. Andrulis (Irene); J.A. Knight (Julia); G. Glendon (Gord); A.-M. Mulligan (Anna-Marie); A. Broeks (Annegien); F.B.L. Hogervorst (Frans); C.A. Haiman (Christopher); B.E. Henderson (Brian); F.R. Schumacher (Fredrick); L. Le Marchand (Loic); J. Hopper (John); H. Tsimiklis (Helen); C. Apicella (Carmel); M.C. Southey (Melissa); A. Cox (Angela); S.S. Cross (Simon); M.W.R. Reed (Malcolm); G.G. Giles (Graham G.); R.L. Milne (Roger L.); C.A. McLean (Catriona Ann); R. Winqvist (Robert); K. Pykäs (Katri); A. Jukkola-Vuorinen (Arja); M. Grip (Mervi); M.J. Hooning (Maartje); A. Hollestelle (Antoinette); J.W.M. Martens (John W. M.); A.M.W. van den Ouweland (Ans); F. Marme (Federick); A. Schneeweiss (Andreas); R. Yang (Rongxi); B. Burwinkel (Barbara); J.D. Figueroa (Jonine); S.J. Chanock (Stephen); J. Lissowska (Jolanta); E.J. Sawyer (Elinor); I.P. Tomlinson (Ian); M. Kerin (Michael); N. Miller (Nicola); H. Brenner (Hermann); A.K. Dieffenbach (Aida Karina); V. Arndt (Volker); B. Holleczek (B.); A. Mannermaa (Arto); V. Kataja (Vesa); V-M. Kosma (Veli-Matti); J.M. Hartikainen (J.); J. Li (Jingmei); J.S. Brand (Judith S.); M.K. Humphreys (Manjeet); P. Devilee (Peter); R.A.E.M. Tollenaar (Rob); C.M. Seynaeve (Caroline); P. Radice (Paolo); P. Peterlongo (Paolo); B. Bonnani (Bernardo); P. Mariani (Paolo); P.A. Fasching (Peter); M.W. Beckmann (Matthias); R. Hein (Rebecca); A.B. Ekici (Arif); G. Chenevix-Trench (Georgia); R. Balleine (Rosemary); K.-A. Phillips (Kelly-Anne); J. Benítez (Javier); M.P. Zamora (Pilar); J.I. Arias Pérez (José Ignacio); P. Menéndez (Primitiva); A. Jakubowska (Anna); J. Lubinski (Jan); K. Jaworska-Bieniek (Katarzyna); K. Durda (Katarzyna); U. Hamann (Ute); M. Kabisch (Maria); H.U. Ulmer (Hans); T. Rud̈iger (Thomas); S. Margolin (Sara); V. Kristensen (Vessela); S. Nord (Silje); D.G. Evans (Gareth); J. Abraham (Jean); H. Earl (Helena); L. Hiller (Louise); J.A. Dunn (J.); S. Bowden (Sarah); C.D. Berg (Christine); D. Campa (Daniele); W.R. Diver (Ryan); S.M. Gapstur (Susan M.); M.M. Gaudet (Mia); S.E. Hankinson (Susan); R.N. Hoover (Robert); A. Hüsing (Anika); R. Kaaks (Rudolf); M.J. Machiela (Mitchell J.); W.C. Willett (Walter C.); M. Barrdahl (Myrto); F. Canzian (Federico); S.-F. Chin (Suet-Feung); C. Caldas (Carlos); D. Hunter (David); S. Lindstrom (Stephen); M. García-Closas (Montserrat); P. Hall (Per); D.F. Easton (Douglas); D. Eccles (Diana); N. Rahman (Nazneen); H. Nevanlinna (Heli); P.D.P. Pharoah (Paul)

    2015-01-01

    textabstractBackground: Survival after a diagnosis of breast cancer varies considerably between patients, and some of this variation may be because of germline genetic variation. We aimed to identify genetic markers associated with breast cancer-specific survival. Methods: We conducted a large

  14. Familial breast cancer: what the radiologist needs to know

    International Nuclear Information System (INIS)

    Kuhl, C.K.

    2006-01-01

    About 10% of breast cancers are ''hereditary'', i.e. caused by a pathogenic mutation in one of the ''breast and ovarian cancer susceptibility genes'' (BRCA). The BRCA genes 1 and 2 identified to date follow an autosomal dominant inheritance pattern. A clustering of breast cancer in a family without a documented mutation and without a recognizable inheritance pattern is usually referred to as ''familial cancer''. A distinction between hereditary and familial is difficult in the individual case because not all of the genetic mutations that cause breast cancer susceptibility are known and thus amenable to genetic testing. Women who are suspected of or documented as carrying a breast cancer susceptibility gene face a substantially increased lifetime risk of breast (and ovarian) cancer ranging from 60-80% for breast and up to 40% for ovarian cancer. In addition, the disease develops at a young age (the personal risk starts increasing at age 25; average age of diagnosis is 40). BRCA-associated breast cancers tend to exhibit histologic and histochemical evidence of aggressive biologic behavior (usually grade 3, receptor negative) with very fast growth rates. In particular BRCA1-associated breast cancer may be indistinguishable from fibroadenomas: They appear as well-defined, roundish, hypoechoic masses with smooth borders, without posterior acoustic shadowing on ultrasound, without associated microcalcifications on mammography, and with strong wash-out phenomenon on breast MRI. This article reviews the different options that exist for the prevention of familial or hereditary breast cancer and the specific difficulties that are associated with the radiological diagnosis of these cancers. Lastly, an overview is given of the current evidence regarding the effectiveness of the different imaging modalities for early diagnosis of familial and hereditary breast cancer. (orig.)

  15. PET imaging in breast cancer

    International Nuclear Information System (INIS)

    Bombardieri, E.; Crippa, F.

    2001-01-01

    The basis of tumour imaging with PET is a specific uptake mechanism of positron emitting radiopharmaceuticals. Among the potential tracers for breast cancer (fluorodeoxyglucose, methionine, tyrosine, fluoro-estradiol, nor-progesterone), 2-deoxy-2-fluoro-D-glucose labelled with fluorine (FDG) is the most widely used radiopharmaceutical because breast cancer is particularly avid of FDG and 18 F has the advantages of the a relatively long physical half-life. Mammography is the first choice examination in studying breast masses, due to its very good performances, an excellent compliance and the best value regarding the cost/effectiveness aspects. The FDG uptake in tissue correlates with the histological grade and potential aggressiveness of breast cancer and this may have prognostic consequences. Besides the evaluation of breast lesions, FDG-PET shows a great efficacy in staging lymph node involvement prior surgery and this could have a great value in loco-regional staging. Whole body PET provides also information with regard to metastasis localizations both in soft tissue and bone, and plays an important clinical role mainly in detecting recurrent metastatic disease. In fact for its metabolic characteristics PET visualizes regions of enhanced metabolic activity and can complete other imaging modalities based on structural anatomic changes. Even though CT and MRI show superior resolution characteristics, it has been demonstrated that PET provides more accurate information in discriminating between viable tumour, fibrotic scar or necrosis. These statements are coming from the examination of more than 2000 breast cancer detection

  16. Breast Cancer Mortality In Brazil: Correlation With Human Development Index

    Directory of Open Access Journals (Sweden)

    Mara Rejane Barroso Barcelos

    2017-01-01

    Full Text Available Background: Mortality from breast cancer decreased in high-income countries, while countries with middle and low incomes as Brazil still has upward trend. However, large geographical variations among the federal units are observed in the country. The aim of the study was to evaluate the trend of specific mortality from breast cancer in women over 20 years old years among different states of Brazil from 1996 to 2012.  Methods and Findings: Ecological study, using linear regression model for temporal analysis of specific mortality coefficient from malignant neoplasm of breast. We also checked the degree of its correlation with the HDI for the states of Brazil during the stated period. There was an increase in the specific mortality rate for malignant neoplasm of the breast in order of 33%, with range from 23.2 to 30.8 / 100,000 inhabitants. The states with the highest human development HDI in 2010, showed the largest specific mortality rates of breast cancer. Conclusion: Taking the trends of mortality from cancer an important role, this study confirms the need for improvements in mammography coverage, following radiological lesions suspected and access to appropriate therapy.

  17. Breast Cancer Risk in American Women

    Science.gov (United States)

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

  18. FGFR2 promotes breast tumorigenicity through maintenance of breast tumor-initiating cells.

    Directory of Open Access Journals (Sweden)

    Sungeun Kim

    Full Text Available Emerging evidence suggests that some cancers contain a population of stem-like TICs (tumor-initiating cells and eliminating TICs may offer a new strategy to develop successful anti-cancer therapies. As molecular mechanisms underlying the maintenance of the TIC pool are poorly understood, the development of TIC-specific therapeutics remains a major challenge. We first identified and characterized TICs and non-TICs isolated from a mouse breast cancer model. TICs displayed increased tumorigenic potential, self-renewal, heterogeneous differentiation, and bipotency. Gene expression analysis and immunostaining of TICs and non-TICs revealed that FGFR2 was preferentially expressed in TICs. Loss of FGFR2 impaired self-renewal of TICs, thus resulting in marked decreases in the TIC population and tumorigenic potential. Restoration of FGFR2 rescued the defects in TIC pool maintenance, bipotency, and breast tumor growth driven by FGFR2 knockdown. In addition, pharmacological inhibition of FGFR2 kinase activity led to a decrease in the TIC population which resulted in suppression of breast tumor growth. Moreover, human breast TICs isolated from patient tumor samples were found enriched in a FGFR2+ population that was sufficient to initiate tumor growth. Our data suggest that FGFR2 is essential in sustaining the breast TIC pool through promotion of self-renewal and maintenance of bipotent TICs, and raise the possibility of FGFR2 inhibition as a strategy for anti-cancer therapy by eradicating breast TICs.

  19. Synthesis and in vitro anti-cancer evaluation of luteinizing hormone-releasing hormone-conjugated peptide.

    Science.gov (United States)

    Deng, Xin; Qiu, Qianqian; Ma, Ke; Huang, Wenlong; Qian, Hai

    2015-11-01

    Luteinizing hormone-releasing hormone (LHRH) is a decapeptide hormone released from the hypothalamus and shows high affinity binding to the LHRH receptors. It is reported that several cancer cells also express LHRH receptors such as breast, ovarian, prostatic, bladder and others. In this study, we linked B1, an anti-cancer peptide, to LHRH and its analogs to improve the activity against cancer cells with LHRH receptor. Biological evaluation revealed that TB1, the peptide contains triptorelin sequence, present favorable anti-cancer activity as well as plasma stability. Further investigations disclosed that TB1 trigger apoptosis by activating the mitochondria-cytochrome c-caspase apoptotic pathway, it also exhibited the anti-migratory effect on cancer cells.

  20. pH-Regulatory Proteins as Potential Targets in Breast Cancer

    DEFF Research Database (Denmark)

    Andersen, Anne Poder

    tissues. The focus of the present PhD study is on understanding the mechanisms through which pH-regulatory transporters are regulated by the breast tumor microenvironment, and how these transporters in turn favor cancer progression. In Paper I, we summarized the recent knowledge on the dynamic...... exhibit distinct spatial organization during 3D growth of MCF-7 and MDA-MB-231 breast cancer cells. By pharmacological inhibition and stable shRNA-mediated knockdown, we addressed the specific contributions of the transporters to spheroid growth and show that the specific transporters contribute to breast...... development in the more complex in vivo setting. In Paper III, we found that chemical induction of breast cancer in NBCn1 knockout (KO) mice is delayed and tumor growth rates reduced, compared to those in wildtype (WT) mice, demonstrating a causal link between NBCn1 and breast cancer development. In Paper IV...

  1. Aberrantly methylated DNA as a biomarker in breast cancer.

    Science.gov (United States)

    Kristiansen, Søren; Jørgensen, Lars M; Guldberg, Per; Sölétormos, György

    2013-01-01

    Aberrant DNA hypermethylation at gene promoters is a frequent event in human breast cancer. Recent genome-wide studies have identified hundreds of genes that exhibit differential methylation between breast cancer cells and normal breast tissue. Due to the tumor-specific nature of DNA hypermethylation events, their use as tumor biomarkers is usually not hampered by analytical signals from normal cells, which is a general problem for existing protein tumor markers used for clinical assessment of breast cancer. There is accumulating evidence that DNA-methylation changes in breast cancer patients occur early during tumorigenesis. This may open up for effective screening, and analysis of blood or nipple aspirate may later help in diagnosing breast cancer. As a more detailed molecular characterization of different types of breast cancer becomes available, the ability to divide patients into subgroups based on DNA biomarkers may improve prognosis. Serial monitoring of DNA-methylation markers in blood during treatment may be useful, particularly when the cancer burden is below the detection level for standard imaging techniques. Overall, aberrant DNA methylation has a great potential as a versatile biomarker tool for screening, diagnosis, prognosis and monitoring of breast cancer. Standardization of methods and biomarker panels will be required to fully exploit this clinical potential.

  2. Mammographic Breast Density in Malaysian Women with Breast Cancer

    International Nuclear Information System (INIS)

    Noriah Jamal; Humairah Samad Cheung

    2016-01-01

    The objective of this study was to examine the mammographic breast density of women with breast cancer detected on voluntary mammographic screening at two selected screening centers in Malaysia. This was a retrospective study of Full-Field Digital Mammography (FFDM) images of 150 Malaysian women with biopsy-proven breast cancer. The study population comprised 73 Malays (37.7 %), 59 Chinese (39.3 %) and 18 Indians (12.0 %). The Tabar breast density Patterns (I - V) were used to evaluate mammographic breast density. Data were analyzed using descriptive statistics. The results were compared with findings from a similar study on a group of 668 women who did not have breast cancer. The results showed that 44.7 % of the study population had dense breasts (Patterns IV and V), 14.7 % had predominantly fatty breasts (Patterns II and III) while 40.7 % had Pattern I. The proportion of study population with dense breasts decreased with age. In conclusion, the proportion of women with dense breasts decreased with age. Majority of the women with cancer (44.7 %) had dense breasts of Tabar Patterns IV and V, which has been associated with increased risk of breast cancer detected by voluntary mammographic screening. The results support the notion that increased breast density is a risk factor of breast cancer. (author)

  3. Space-time clusters of breast cancer using residential histories

    DEFF Research Database (Denmark)

    Nordsborg, Rikke Baastrup; Meliker, Jaymie R; Ersbøll, Annette Kjær

    2014-01-01

    BACKGROUND: A large proportion of breast cancer cases are thought related to environmental factors. Identification of specific geographical areas with high risk (clusters) may give clues to potential environmental risk factors. The aim of this study was to investigate whether clusters of breast...... cancer existed in space and time in Denmark, using 33 years of residential histories. METHODS: We conducted a population-based case-control study of 3138 female cases from the Danish Cancer Registry, diagnosed with breast cancer in 2003 and two independent control groups of 3138 women each, randomly...

  4. GU81, a VEGFR2 antagonist peptoid, enhances the anti-tumor activity of doxorubicin in the murine MMTV-PyMT transgenic model of breast cancer

    International Nuclear Information System (INIS)

    Lynn, Kristi D; Udugamasooriya, D Gomika; Roland, Christina L; Castrillon, Diego H; Kodadek, Thomas J; Brekken, Rolf A

    2010-01-01

    Vascular endothelial growth factor (VEGF) is a primary stimulant of angiogenesis under physiological and pathological conditions. Anti-VEGF therapy is a clinically proven strategy for the treatment of a variety of cancers including colon, breast, lung, and renal cell carcinoma. Since VEGFR2 is the dominant angiogenic signaling receptor, it has become an important target in the development of novel anti-angiogenic therapies. We have reported previously the development of an antagonistic VEGFR2 peptoid (GU40C4) that has promising anti-angiogenic activity in vitro and in vivo. In the current study, we utilize a derivative of GU40C4, termed GU81 in therapy studies. GU81 was tested alone or in combination with doxorubicin for in vivo efficacy in the MMTV-PyMT transgenic model of breast cancer. The derivative GU81 has increased in vitro efficacy compared to GU40C4. Single agent therapy (doxorubicin or GU81 alone) had no effect on tumor weight, histology, tumor fat content, or tumor growth index. However, GU81 is able to significantly to reduce total vascular area as a single agent. GU81 used in combination with doxorubicin significantly reduced tumor weight and growth index compared to all other treatment groups. Furthermore, treatment with combination therapy significantly arrested tumor progression at the premalignant stage, resulting in increased tumor fat content. Interestingly, treatment with GU81 alone increased tumor-VEGF levels and macrophage infiltration, an effect that was abrogated when used in combination with doxorubicin. This study demonstrates the VEGFR2 antagonist peptoid, GU81, enhances the anti-tumor activity of doxorubicin in spontaneous murine MMTV-PyMT breast tumors

  5. Signaling Network Assessment of Mutations and Copy Number Variations Predict Breast Cancer Subtype-Specific Drug Targets

    Directory of Open Access Journals (Sweden)

    Naif Zaman

    2013-10-01

    Full Text Available Individual cancer cells carry a bewildering number of distinct genomic alterations (e.g., copy number variations and mutations, making it a challenge to uncover genomic-driven mechanisms governing tumorigenesis. Here, we performed exome sequencing on several breast cancer cell lines that represent two subtypes, luminal and basal. We integrated these sequencing data and functional RNAi screening data (for the identification of genes that are essential for cell proliferation and survival onto a human signaling network. Two subtype-specific networks that potentially represent core-signaling mechanisms underlying tumorigenesis were identified. Within both networks, we found that genes were differentially affected in different cell lines; i.e., in some cell lines a gene was identified through RNAi screening, whereas in others it was genomically altered. Interestingly, we found that highly connected network genes could be used to correctly classify breast tumors into subtypes on the basis of genomic alterations. Further, the networks effectively predicted subtype-specific drug targets, which were experimentally validated.

  6. Protein tyrosine phosphatase µ (PTP µ or PTPRM, a negative regulator of proliferation and invasion of breast cancer cells, is associated with disease prognosis.

    Directory of Open Access Journals (Sweden)

    Ping-Hui Sun

    Full Text Available BACKGROUND: PTPRM has been shown to exhibit homophilic binding and confer cell-cell adhesion in cells including epithelial and cancer cells. The present study investigated the expression of PTPRM in breast cancer and the biological impact of PTPRM on breast cancer cells. DESIGN: Expression of PTPRM protein and gene transcript was examined in a cohort of breast cancer patients. Knockdown of PTPRM in breast cancer cells was performed using a specific anti-PTPRM transgene. The impact of PTPRM knockdown on breast cancer was evaluated using in vitro cell models. RESULTS: A significant decrease of PTPRM transcripts was seen in poorly differentiated and moderately differentiated tumours compared with well differentiated tumours. Patients with lower expression of PTPRM had shorter survival compared with those which had a higher level of PTPRM expression. Knockdown of PTPRM increased proliferation, adhesion, invasion and migration of breast cancer cells. Furthermore, knockdown of PTPRM in MDA-MB-231 cells resulted in increased cell migration and invasion via regulation of the tyrosine phosphorylation of ERK and JNK. CONCLUSIONS: Decreased expression of PTPRM in breast cancer is correlated with poor prognosis and inversely correlated with disease free survival. PTPRM coordinated cell migration and invasion through the regulation of tyrosine phosphorylation of ERK and JNK.

  7. Engineered Autologous Stromal Cells for the Delivery of Kringle 5, a Potent Endothelial Cell Specific Inhibitor for Anti-Angiogenic Breast Cancer Therapy

    National Research Council Canada - National Science Library

    Perri, Sabrina R

    2006-01-01

    .... To determine whether K5 possesses immune proinflammatory properties, we investigated the effects of K5 in an immune competent model of breast cancer and observed that tumor rejection is substantially...

  8. Complimentary mechanisms of dual checkpoint blockade expand unique T-cell repertoires and activate adaptive anti-tumor immunity in triple-negative breast tumors

    Science.gov (United States)

    Wei, Junping; Yang, Xiao Yi; Lei, Gangjun; Wang, Tao; Liu, Cong-Xiao; Morse, Michael A.; Gouin, Kenneth; Knott, Simon R. V.; Hartman, Zachary C.

    2018-01-01

    ABSTRACT Triple-negative breast cancer (TNBC) is an aggressive and molecularly diverse breast cancer subtype typified by the presence of p53 mutations (∼80%), elevated immune gene signatures and neoantigen expression, as well as the presence of tumor infiltrating lymphocytes (TILs). As these factors are hypothesized to be strong immunologic prerequisites for the use of immune checkpoint blockade (ICB) antibodies, multiple clinical trials testing single ICBs have advanced to Phase III, with early indications of heterogeneous response rates of <20% to anti-PD1 and anti-PDL1 ICB. While promising, these modest response rates highlight the need for mechanistic studies to understand how different ICBs function, how their combination impacts functionality and efficacy, as well as what immunologic parameters predict efficacy to different ICBs regimens in TNBC. To address these issues, we tested anti-PD1 and anti-CTLA4 in multiple models of TNBC and found that their combination profoundly enhanced the efficacy of either treatment alone. We demonstrate that this efficacy is due to anti-CTLA4-driven expansion of an individually unique T-cell receptor (TCR) repertoire whose functionality is enhanced by both intratumoral Treg suppression and anti-PD1 blockade of tumor expressed PDL1. Notably, the individuality of the TCR repertoire was observed regardless of whether the tumor cells expressed a nonself antigen (ovalbumin) or if tumor-specific transgenic T-cells were transferred prior to sequencing. However, responsiveness was strongly correlated with systemic measures of tumor-specific T-cell and B-cell responses, which along with systemic assessment of TCR expansion, may serve as the most useful predictors for clinical responsiveness in future clinical trials of TNBC utilizing anti-PD1/anti-CTLA4 ICB. PMID:29721371

  9. Complimentary mechanisms of dual checkpoint blockade expand unique T-cell repertoires and activate adaptive anti-tumor immunity in triple-negative breast tumors.

    Science.gov (United States)

    Crosby, Erika J; Wei, Junping; Yang, Xiao Yi; Lei, Gangjun; Wang, Tao; Liu, Cong-Xiao; Agarwal, Pankaj; Korman, Alan J; Morse, Michael A; Gouin, Kenneth; Knott, Simon R V; Lyerly, H Kim; Hartman, Zachary C

    2018-01-01

    Triple-negative breast cancer (TNBC) is an aggressive and molecularly diverse breast cancer subtype typified by the presence of p53 mutations (∼80%), elevated immune gene signatures and neoantigen expression, as well as the presence of tumor infiltrating lymphocytes (TILs). As these factors are hypothesized to be strong immunologic prerequisites for the use of immune checkpoint blockade (ICB) antibodies, multiple clinical trials testing single ICBs have advanced to Phase III, with early indications of heterogeneous response rates of <20% to anti-PD1 and anti-PDL1 ICB. While promising, these modest response rates highlight the need for mechanistic studies to understand how different ICBs function, how their combination impacts functionality and efficacy, as well as what immunologic parameters predict efficacy to different ICBs regimens in TNBC. To address these issues, we tested anti-PD1 and anti-CTLA4 in multiple models of TNBC and found that their combination profoundly enhanced the efficacy of either treatment alone. We demonstrate that this efficacy is due to anti-CTLA4-driven expansion of an individually unique T-cell receptor (TCR) repertoire whose functionality is enhanced by both intratumoral Treg suppression and anti-PD1 blockade of tumor expressed PDL1. Notably, the individuality of the TCR repertoire was observed regardless of whether the tumor cells expressed a nonself antigen (ovalbumin) or if tumor-specific transgenic T-cells were transferred prior to sequencing. However, responsiveness was strongly correlated with systemic measures of tumor-specific T-cell and B-cell responses, which along with systemic assessment of TCR expansion, may serve as the most useful predictors for clinical responsiveness in future clinical trials of TNBC utilizing anti-PD1/anti-CTLA4 ICB.

  10. HIV tropism and decreased risk of breast cancer.

    Directory of Open Access Journals (Sweden)

    Nancy A Hessol

    2010-12-01

    Full Text Available During the first two decades of the U.S. AIDS epidemic, and unlike some malignancies, breast cancer risk was significantly lower for women with human immunodeficiency virus (HIV infection compared to the general population. This deficit in HIV-associated breast cancer could not be attributed to differences in survival, immune deficiency, childbearing or other breast cancer risk factors. HIV infects mononuclear immune cells by binding to the CD4 molecule and to CCR5 or CXCR4 chemokine coreceptors. Neoplastic breast cells commonly express CXCR4 but not CCR5. In vitro, binding HIV envelope protein to CXCR4 has been shown to induce apoptosis of neoplastic breast cells. Based on these observations, we hypothesized that breast cancer risk would be lower among women with CXCR4-tropic HIV infection.We conducted a breast cancer nested case-control study among women who participated in the WIHS and HERS HIV cohort studies with longitudinally collected risk factor data and plasma. Cases were HIV-infected women (mean age 46 years who had stored plasma collected within 24 months of breast cancer diagnosis and an HIV viral load≥500 copies/mL. Three HIV-infected control women, without breast cancer, were matched to each case based on age and plasma collection date. CXCR4-tropism was determined by a phenotypic tropism assay. Odds ratios (OR and 95% confidence intervals (CI for breast cancer were estimated by exact conditional logistic regression. Two (9% of 23 breast cancer cases had CXCR4-tropic HIV, compared to 19 (28% of 69 matched controls. Breast cancer risk was significantly and independently reduced with CXCR4 tropism (adjusted odds ratio, 0.10, 95% CI 0.002-0.84 and with menopause (adjusted odds ratio, 0.08, 95% CI 0.001-0.83. Adjustment for CD4+ cell count, HIV viral load, and use of antiretroviral therapy did not attenuate the association between infection with CXCR4-tropic HIV and breast cancer.Low breast cancer risk with HIV is specifically linked

  11. Claudin-Low Breast Cancer; Clinical & Pathological Characteristics.

    Directory of Open Access Journals (Sweden)

    Kay Dias

    Full Text Available Claudin-low breast cancer is a molecular type of breast cancer originally identified by gene expression profiling and reportedly associated with poor survival. Claudin-low tumors have been recognised to preferentially display a triple-negative phenotype, however only a minority of triple-negative breast cancers are claudin-low. We sought to identify an immunohistochemical profile for claudin-low tumors that could facilitate their identification in formalin fixed paraffin embedded tumor material. First, an in silico collection of ~1600 human breast cancer expression profiles was assembled and all claudin-low tumors identified. Second, genes differentially expressed between claudin-low tumors and all other molecular subtypes of breast cancer were identified. Third, a number of these top differentially expressed genes were tested using immunohistochemistry for expression in a diverse panel of breast cancer cell lines to determine their specificity for claudin-low tumors. Finally, the immunohistochemical panel found to be most characteristic of claudin-low tumors was examined in a cohort of 942 formalin fixed paraffin embedded human breast cancers with >10 years clinical follow-up to evaluate the clinico-pathologic and survival characteristics of this tumor subtype. Using this approach we determined that claudin-low breast cancer is typically negative for ER, PR, HER2, claudin 3, claudin 4, claudin 7 and E-cadherin. Claudin-low tumors identified with this immunohistochemical panel, were associated with young age of onset, higher tumor grade, larger tumor size, extensive lymphocytic infiltrate and a circumscribed tumor margin. Patients with claudin-low tumors had a worse overall survival when compared to patients with luminal A type breast cancer. Interestingly, claudin-low tumors were associated with a low local recurrence rate following breast conserving therapy. In conclusion, a limited panel of antibodies can facilitate the identification of

  12. A New Model for the Estimation of Breast Cancer Risk

    National Research Council Canada - National Science Library

    Giger, Maryellen Lissak

    2001-01-01

    ... for use in estimating risk of breast cancer. The specific aims include 1. Creating a database of mammograms, along with tabulated clinical information of women at low risk and high risk for breast cancer; 2...

  13. Endostatin gene variation and protein levels in breast cancer susceptibility and severity

    International Nuclear Information System (INIS)

    Balasubramanian, Sabapathy P; Cross, Simon S; Globe, Jenny; Cox, Angela; Brown, Nicola J; Reed, Malcolm W

    2007-01-01

    Endostatin is a potent endogenous anti-angiogenic agent which inhibits tumour growth. A non-synonymous coding polymorphism in the Endostatin gene is thought to affect Endostatin activity. We aimed to determine the role of this Endostatin polymorphism in breast cancer pathogenesis and any influence on serum Endostatin levels in healthy volunteers. Endostatin protein expression on a breast cancer micro array was also studied to determine any relationship to genotype and to breast cancer prognosis. The 4349G > A (coding non-synonymous) polymorphism in exon 42 of the Endostatin gene was genotyped in approximately 846 breast cancer cases and 707 appropriate controls. In a separate healthy cohort of 57 individuals, in addition to genotyping, serum Endostatin levels were measured using enzyme linked immunosorbant assay (ELISA). A semi-quantitative assessment of Endostatin protein expression on immunostained tissue micro arrays (TMA) constructed from breast cancer samples of patients with genotype data was performed. The rare allele (A) was significantly associated with invasive breast cancers compared to non-invasive tumours (p = 0.03), but there was no association with tumour grade, nodal status, vascular invasion or overall survival. There was no association with breast cancer susceptibility. Serum Endostatin levels and Endostatin protein expression on the tissue micro array were not associated with genotype. The Endostatin 4349A allele is associated with invasive breast cancer. The Endostatin 4349G > A polymorphism however does not appear to be associated with breast cancer susceptibility or severity in invasive disease. By studying circulating levels and tumour Endostatin protein expression, we have shown that any influence of this polymorphism is unlikely to be through an effect on the levels of protein produced

  14. Natural product ginsenoside 25-OCH3-PPD inhibits breast cancer growth and metastasis through down-regulating MDM2.

    Science.gov (United States)

    Wang, Wei; Zhang, Xu; Qin, Jiang-Jiang; Voruganti, Sukesh; Nag, Subhasree Ashok; Wang, Ming-Hai; Wang, Hui; Zhang, Ruiwen

    2012-01-01

    Although ginseng and related herbs have a long history of utility for various health benefits, their application in cancer therapy and underlying mechanisms of action are not fully understood. Our recent work has shown that 20(S)-25-methoxyl-dammarane-3β, 12β, 20-triol (25-OCH(3)-PPD), a newly identified ginsenoside from Panax notoginseng, exerts activities against a variety of cancer cells in vitro and in vivo. This study was designed to investigate its anti-breast cancer activity and the underlying mechanisms of action. We observed that 25-OCH(3)-PPD decreased the survival of breast cancer cells by induction of apoptosis and G1 phase arrest and inhibited the growth of breast cancer xenografts in vivo. We further demonstrated that, in a dose- and time-dependent manner, 25-OCH(3)-PPD inhibited MDM2 expression at both transcriptional and post-translational levels in human breast cancer cells with various p53 statuses (wild type and mutant). Moreover, 25-OCH(3)-PPD inhibited in vitro cell migration, reduced the expression of epithelial-to-mesenchymal transition (EMT) markers, and prevented in vivo metastasis of breast cancer. In summary, 25-OCH(3)-PPD is a potential therapeutic and anti-metastatic agent for human breast cancer through down-regulating MDM2. Further preclinical and clinical development of this agent is warranted.

  15. False-positive findings in mammography screening induces short-term distress - breast cancer-specific concern prevails longer

    DEFF Research Database (Denmark)

    Aro, A R; Pilvikki Absetz, S; van Elderen, T M

    2000-01-01

    The aim of this study was to examine psychological distress in a mammography screening process as a consequence of screening after adjusting for background, personality and prescreening distress. Subjects, aged 50 years, were invitees at their first screening. There were three groups; normal find...... perceived breast cancer risk and susceptibility. Distress related to screening and false-positive findings seems to be moderate, but prevailing cancer-specific concerns call for improvements in screening programmes....

  16. A Phenotypic Cell-Binding Screen Identifies a Novel Compound Targeting Triple-Negative Breast Cancer.

    Science.gov (United States)

    Chen, Luxi; Long, Chao; Youn, Jonghae; Lee, Jiyong

    2018-06-11

    We describe a "phenotypic cell-binding screen" by which therapeutic candidate targeting cancer cells of a particular phenotype can be isolated without knowledge of drug targets. Chemical library beads are incubated with cancer cells of the phenotype of interest in the presence of cancer cells lacking the phenotype of interest, and then the beads bound to only cancer cells of the phenotype of interest are selected as hits. We have applied this screening strategy in discovering a novel compound (LC129-8) targeting triple-negative breast cancer (TNBC). LC129-8 displayed highly specific binding to TNBC in cancer cell lines and patient-derived tumor tissues. LC129-8 exerted anti-TNBC activity by inducing apoptosis, inhibiting proliferation, reversing epithelial-mesenchymal transition, downregulating cancer stem cell activity and blocking in vivo tumor growth.

  17. Diabetes and Breast Cancer Subtypes.

    Directory of Open Access Journals (Sweden)

    Heleen K Bronsveld

    Full Text Available Women with diabetes have a worse survival after breast cancer diagnosis compared to women without diabetes. This may be due to a different etiological profile, leading to the development of more aggressive breast cancer subtypes. Our aim was to investigate whether insulin and non-insulin treated women with diabetes develop specific clinicopathological breast cancer subtypes compared to women without diabetes.This cross-sectional study included randomly selected patients with invasive breast cancer diagnosed in 2000-2010. Stratified by age at breast cancer diagnosis (≤50 and >50 years, women with diabetes were 2:1 frequency-matched on year of birth and age at breast cancer diagnosis (both in 10-year categories to women without diabetes, to select ~300 patients with tumor tissue available. Tumor MicroArrays were stained by immunohistochemistry for estrogen and progesterone receptor (ER, PR, HER2, Ki67, CK5/6, CK14, and p63. A pathologist scored all stains and revised morphology and grade. Associations between diabetes/insulin treatment and clinicopathological subtypes were analyzed using multivariable logistic regression. Morphology and grade were not significantly different between women with diabetes (n = 211 and women without diabetes (n = 101, irrespective of menopausal status. Premenopausal women with diabetes tended to have more often PR-negative (OR = 2.44(95%CI:1.07-5.55, HER2-negative (OR = 2.84(95%CI:1.11-7.22, and basal-like (OR = 3.14(95%CI:1.03-9.60 tumors than the women without diabetes, with non-significantly increased frequencies of ER-negative (OR = 2.48(95%CI:0.95-6.45 and triple negative (OR = 2.60(95%CI:0.88-7.67 tumors. After adjustment for age and BMI, the associations remained similar in size but less significant. We observed no evidence for associations of clinicopathological subtypes with diabetes in postmenopausal women, or with insulin treatment in general.We found no compelling evidence that women with diabetes

  18. Diabetes and Breast Cancer Subtypes.

    Science.gov (United States)

    Bronsveld, Heleen K; Jensen, Vibeke; Vahl, Pernille; De Bruin, Marie L; Cornelissen, Sten; Sanders, Joyce; Auvinen, Anssi; Haukka, Jari; Andersen, Morten; Vestergaard, Peter; Schmidt, Marjanka K

    2017-01-01

    Women with diabetes have a worse survival after breast cancer diagnosis compared to women without diabetes. This may be due to a different etiological profile, leading to the development of more aggressive breast cancer subtypes. Our aim was to investigate whether insulin and non-insulin treated women with diabetes develop specific clinicopathological breast cancer subtypes compared to women without diabetes. This cross-sectional study included randomly selected patients with invasive breast cancer diagnosed in 2000-2010. Stratified by age at breast cancer diagnosis (≤50 and >50 years), women with diabetes were 2:1 frequency-matched on year of birth and age at breast cancer diagnosis (both in 10-year categories) to women without diabetes, to select ~300 patients with tumor tissue available. Tumor MicroArrays were stained by immunohistochemistry for estrogen and progesterone receptor (ER, PR), HER2, Ki67, CK5/6, CK14, and p63. A pathologist scored all stains and revised morphology and grade. Associations between diabetes/insulin treatment and clinicopathological subtypes were analyzed using multivariable logistic regression. Morphology and grade were not significantly different between women with diabetes (n = 211) and women without diabetes (n = 101), irrespective of menopausal status. Premenopausal women with diabetes tended to have more often PR-negative (OR = 2.44(95%CI:1.07-5.55)), HER2-negative (OR = 2.84(95%CI:1.11-7.22)), and basal-like (OR = 3.14(95%CI:1.03-9.60) tumors than the women without diabetes, with non-significantly increased frequencies of ER-negative (OR = 2.48(95%CI:0.95-6.45)) and triple negative (OR = 2.60(95%CI:0.88-7.67) tumors. After adjustment for age and BMI, the associations remained similar in size but less significant. We observed no evidence for associations of clinicopathological subtypes with diabetes in postmenopausal women, or with insulin treatment in general. We found no compelling evidence that women with diabetes, treated

  19. Do we need regional guidelines for breast cancer management in the MENA region? MENA Breast Cancer Guidelines project.

    Science.gov (United States)

    Fayed, Reham; Hamza, Dina; Abdallah, Heba; Kelany, Mohamed; Tahseen, Amira; Aref, Adel T

    2017-01-01

    region. Creating a national breast screening programme and a reliable database is essential. A regional guideline is required to establish the best possible management of breast cancer according to the patients and disease specification as well as the regional socioeconomic factors and facilities available. There is also a need to improve clinical research that meets the region's needs.

  20. Prevention and Treatment of Bone Metastases in Breast Cancer

    Directory of Open Access Journals (Sweden)

    Ripamonti Carla

    2013-09-01

    Full Text Available In breast cancer patients, bone is the most common site of metastases. Medical therapies are the basic therapy to prevent distant metastases and recurrence and to cure them. Radiotherapy has a primary role in pain relief, recalcification and stabilization of the bone, as well as the reduction of the risk of complications (e.g., bone fractures, spinal cord compression. Bisphosphonates, as potent inhibitors of osteoclastic-mediated bone resorption are a well-established, standard-of-care treatment option to reduce the frequency, severity and time of onset of the skeletal related events in breast cancer patients with bone metastases. Moreover bisphosphonates prevent cancer treatment-induced bone loss. Recent data shows the anti-tumor activity of bisphosphonates, in particular, in postmenopausal women and in older premenopausal women with hormone-sensitive disease treated with ovarian suppression. Pain is the most frequent symptom reported in patients with bone metastases, and its prevention and treatment must be considered at any stage of the disease. The prevention and treatment of bone metastases in breast cancer must consider an integrated multidisciplinary approach.

  1. Up-regulation of METCAM/MUC18 promotes motility, invasion, and tumorigenesis of human breast cancer cells

    International Nuclear Information System (INIS)

    Zeng, Guo-fang; Cai, Shao-xi; Wu, Guang-Jer

    2011-01-01

    Conflicting research has identified METCAM/MUC18, an integral membrane cell adhesion molecule (CAM) in the Ig-like gene super-family, as both a tumor promoter and a tumor suppressor in the development of breast cancer. To resolve this, we have re-investigated the role of this CAM in the progression of human breast cancer cells. Three breast cancer cell lines were used for the tests: one luminal-like breast cancer cell line, MCF7, which did not express any METCAM/MUC18, and two basal-like breast cancer cell lines, MDA-MB-231 and MDA-MB-468, which expressed moderate levels of the protein. MCF7 cells were transfected with the human METCAM/MUC18 cDNA to obtain G418-resistant clones which expressed the protein and were used for testing effects of human METCAM/MUC18 expression on in vitro motility and invasiveness, and in vitro and in vivo tumorigenesis. Both MDA-MB-231 and MDA-MB-468 cells already expressed METCAM/MUC18. They were directly used for in vitro tests in the presence and absence of an anti-METCAM/MUC18 antibody. In MCF7 cells, enforced METCAM/MUC18 expression increased in vitro motility, invasiveness, anchorage-independent colony formation (in vitro tumorigenesis), and in vivo tumorigenesis. In both MDA-MB-231 and MDA-MB-468 cells, the anti-METCAM/MUC18 antibody inhibited both motility and invasiveness. Though both MDA-MB-231 and MDA-MB-468 cells established a disorganized growth in 3D basement membrane culture assay, the introduction of the anti-METCAM/MUC18 antibody completely destroyed their growth in the 3D culture. These findings support the notion that human METCAM/MUC18 expression promotes the progression of human breast cancer cells by increasing their motility, invasiveness and tumorigenesis

  2. Up-regulation of METCAM/MUC18 promotes motility, invasion, and tumorigenesis of human breast cancer cells

    Directory of Open Access Journals (Sweden)

    Cai Shao-xi

    2011-03-01

    Full Text Available Abstract Background Conflicting research has identified METCAM/MUC18, an integral membrane cell adhesion molecule (CAM in the Ig-like gene super-family, as both a tumor promoter and a tumor suppressor in the development of breast cancer. To resolve this, we have re-investigated the role of this CAM in the progression of human breast cancer cells. Methods Three breast cancer cell lines were used for the tests: one luminal-like breast cancer cell line, MCF7, which did not express any METCAM/MUC18, and two basal-like breast cancer cell lines, MDA-MB-231 and MDA-MB-468, which expressed moderate levels of the protein. MCF7 cells were transfected with the human METCAM/MUC18 cDNA to obtain G418-resistant clones which expressed the protein and were used for testing effects of human METCAM/MUC18 expression on in vitro motility and invasiveness, and in vitro and in vivo tumorigenesis. Both MDA-MB-231 and MDA-MB-468 cells already expressed METCAM/MUC18. They were directly used for in vitro tests in the presence and absence of an anti-METCAM/MUC18 antibody. Results In MCF7 cells, enforced METCAM/MUC18 expression increased in vitro motility, invasiveness, anchorage-independent colony formation (in vitro tumorigenesis, and in vivo tumorigenesis. In both MDA-MB-231 and MDA-MB-468 cells, the anti-METCAM/MUC18 antibody inhibited both motility and invasiveness. Though both MDA-MB-231 and MDA-MB-468 cells established a disorganized growth in 3D basement membrane culture assay, the introduction of the anti-METCAM/MUC18 antibody completely destroyed their growth in the 3D culture. Conclusion These findings support the notion that human METCAM/MUC18 expression promotes the progression of human breast cancer cells by increasing their motility, invasiveness and tumorigenesis.

  3. Detection of Methylated Circulating DNA as Noninvasive Biomarkers for Breast Cancer Diagnosis

    Science.gov (United States)

    Cheuk, Isabella Wai Yin; Shin, Vivian Yvonne

    2017-01-01

    Internationally, breast cancer is the most common female cancer, and is induced by a combination of environmental, genetic, and epigenetic risk factors. Despite the advancement of imaging techniques, invasive sampling of breast epithelial cells is the only definitive diagnostic procedure for patients with breast cancer. To date, molecular biomarkers with high sensitivity and specificity for the screening and early detection of breast cancer are lacking. Recent evidence suggests that the detection of methylated circulating cell-free DNA in the peripheral blood of patients with cancer may be a promising quantitative and noninvasive method for cancer diagnosis. Methylation detection based on a multi-gene panel, rather than on the methylation status of a single gene, may be used to increase the sensitivity and specificity of breast cancer screening. In this review, the results of 14 relevant studies, investigating the efficacy of cell-free DNA methylation screening for breast cancer diagnosis, have been summarized. The genetic risk factors for breast cancer, the methods used for breast cancer detection, and the techniques and limitations related to the detection of cell-free DNA methylation status, have also been reviewed and discussed. From this review, we conclude that the analysis of peripheral blood or other samples to detect differentially methylated cell-free DNA is a promising technique for use in clinical settings, and may improve the sensitivity of screening for both, early detection and disease relapse, and thus improve the future prognosis of patients with breast cancer. PMID:28382090

  4. Comprehensive analysis of NuMA variation in breast cancer

    Directory of Open Access Journals (Sweden)

    Aittomäki Kristiina

    2008-03-01

    Full Text Available Abstract Background A recent genome wide case-control association study identified NuMA region on 11q13 as a candidate locus for breast cancer susceptibility. Specifically, the variant Ala794Gly was suggested to be associated with increased risk of breast cancer. Methods In order to evaluate the NuMa gene for breast cancer susceptibility, we have here screened the entire coding region and exon-intron boundaries of NuMa in 92 familial breast cancer patients and constructed haplotypes of the identified variants. Five missense variants were further screened in 341 breast cancer cases with a positive family history and 368 controls. We examined the frequency of Ala794Gly in an extensive series of familial (n = 910 and unselected (n = 884 breast cancer cases and controls (n = 906, with a high power to detect the suggested breast cancer risk. We also tested if the variant is associated with histopathologic features of breast tumors. Results Screening of NuMA resulted in identification of 11 exonic variants and 12 variants in introns or untranslated regions. Five missense variants that were further screened in breast cancer cases with a positive family history and controls, were each carried on a unique haplotype. None of the variants, or the haplotypes represented by them, was associated with breast cancer risk although due to low power in this analysis, very low risk alleles may go unrecognized. The NuMA Ala794Gly showed no difference in frequency in the unselected breast cancer case series or familial case series compared to control cases. Furthermore, Ala794Gly did not show any significant association with histopathologic characteristics of the tumors, though Ala794Gly was slightly more frequent among unselected cases with lymph node involvement. Conclusion Our results do not support the role of NuMA variants as breast cancer susceptibility alleles.

  5. Comprehensive analysis of NuMA variation in breast cancer

    International Nuclear Information System (INIS)

    Kilpivaara, Outi; Rantanen, Matias; Tamminen, Anitta; Aittomäki, Kristiina; Blomqvist, Carl; Nevanlinna, Heli

    2008-01-01

    A recent genome wide case-control association study identified NuMA region on 11q13 as a candidate locus for breast cancer susceptibility. Specifically, the variant Ala794Gly was suggested to be associated with increased risk of breast cancer. In order to evaluate the NuMa gene for breast cancer susceptibility, we have here screened the entire coding region and exon-intron boundaries of NuMa in 92 familial breast cancer patients and constructed haplotypes of the identified variants. Five missense variants were further screened in 341 breast cancer cases with a positive family history and 368 controls. We examined the frequency of Ala794Gly in an extensive series of familial (n = 910) and unselected (n = 884) breast cancer cases and controls (n = 906), with a high power to detect the suggested breast cancer risk. We also tested if the variant is associated with histopathologic features of breast tumors. Screening of NuMA resulted in identification of 11 exonic variants and 12 variants in introns or untranslated regions. Five missense variants that were further screened in breast cancer cases with a positive family history and controls, were each carried on a unique haplotype. None of the variants, or the haplotypes represented by them, was associated with breast cancer risk although due to low power in this analysis, very low risk alleles may go unrecognized. The NuMA Ala794Gly showed no difference in frequency in the unselected breast cancer case series or familial case series compared to control cases. Furthermore, Ala794Gly did not show any significant association with histopathologic characteristics of the tumors, though Ala794Gly was slightly more frequent among unselected cases with lymph node involvement. Our results do not support the role of NuMA variants as breast cancer susceptibility alleles

  6. Benign breast disease, mammographic breast density, and the risk of breast cancer.

    Science.gov (United States)

    Tice, Jeffrey A; O'Meara, Ellen S; Weaver, Donald L; Vachon, Celine; Ballard-Barbash, Rachel; Kerlikowske, Karla

    2013-07-17

    Benign breast disease and high breast density are prevalent, strong risk factors for breast cancer. Women with both risk factors may be at very high risk. We included 42818 women participating in the Breast Cancer Surveillance Consortium who had no prior diagnosis of breast cancer and had undergone at least one benign breast biopsy and mammogram; 1359 women developed incident breast cancer in 6.1 years of follow-up (78.1% invasive, 21.9% ductal carcinoma in situ). We calculated hazard ratios (HRs) using Cox regression analysis. The referent group was women with nonproliferative changes and average density. All P values are two-sided. Benign breast disease and breast density were independently associated with breast cancer. The combination of atypical hyperplasia and very high density was uncommon (0.6% of biopsies) but was associated with the highest risk for breast cancer (HR = 5.34; 95% confidence interval [CI] = 3.52 to 8.09, P < .001). Proliferative disease without atypia (25.6% of biopsies) was associated with elevated risk that varied little across levels of density: average (HR = 1.37; 95% CI = 1.11 to 1.69, P = .003), high (HR = 2.02; 95% CI = 1.68 to 2.44, P < .001), or very high (HR = 2.05; 95% CI = 1.54 to 2.72, P < .001). Low breast density (4.5% of biopsies) was associated with low risk (HRs <1) for all benign pathology diagnoses. Women with high breast density and proliferative benign breast disease are at very high risk for future breast cancer. Women with low breast density are at low risk, regardless of their benign pathologic diagnosis.

  7. Hormones and breast cancer: can we use them in ways that could reduce the risk?

    Directory of Open Access Journals (Sweden)

    Khalid Mahmud

    2011-12-01

    Full Text Available Many hormones promote or inhibit breast cancer in different ways. These effects and the mechanisms involved are reviewed in order to suggest a potentially safer use of hormones. Natural estrogens, administered transdermally, and natural progesterone may be the safest combination of female hormones. Increased intake of cruciferous vegetables could provide additional safety by improving 2-hydoxyestrone and diminishing 16 alphahydroxyestrone. Testosterone and dehydroepiandrosterone (DHEA may directly inhibit breast cancer, but could potentially stimulate it by being aromatized into estrogen in the breast. Modest doses with blood level monitoring appear logical. Melatonin and oxytocin are inhibitory to breast and other cancers. Insulin is a growth factor for breast cancer. Managing insulin resistance before the onset of diabetes could reduce the risk. Tri-iodothyronine (T3 has multiple anti-breast cancer effects. Synthroid may not increase T3 levels adequately. Human growth hormone does not appear to increase risk; but it should not be given for performance enhancement.

  8. [Organized breast cancer screening].

    Science.gov (United States)

    Rouëssé, Jacques; Sancho-Garnier, Hélèn

    2014-02-01

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

  9. Ultrastable Nontoxic RNA Nanoparticles for Targeting Triple-Negative Breast Cancer Stem Cells

    Science.gov (United States)

    2016-04-01

    of the 20-F modified 3WJ-EGFRapt/ anti-miR-21 nanoparticles was studied using the TGGE system (Biometra GmbH, Germany ). One of the fragments (c3WJ...MicroRNA Gene Expression Deregulation in Human Breast Cancer. Cancer Res. 2005, 65, 7065–7070. 8. Croce, C. M.; Calin, G. A. MiRNAs, Cancer, and Stem Cell

  10. Serum endocan level and its prognostic significance in breast cancer patients

    Directory of Open Access Journals (Sweden)

    Ozturk Ates

    2018-04-01

    Full Text Available Background: Endocan, known as endothelial cell specific molecule (ESM, is a novel endothelial dysfunction marker. The aim of this study is to examine the plasma endocan level and its prognostic significance in newly diagnosed breast cancer patients. Methods: A total of 84 patients were enrolled the study. Plasma endocan level was measured by specific enzyme-linked immunosorbent assay (ELİSA kit. Ethical approval and informed consent were attained. Results: At the time of diagnosis, 33 patients had stage 4 disease. The median plasma endocan level was 619.9 (min 259.9–2813.2 ng/L and its level was significantly higher in metastatic breast cancer group compared to non–metastatic breast cancer group. According to molecular sub-type of breast cancer, there is not statistical difference in plasma endocan level, but its level was higher in patients with Her-2 amplified and triple negative breast cancer (TNBC. Median follow-up time is 11 (1-30 months. Event free survival (EFS was 15 months in patients with plasma endocan level lower than 620, while it was 4 months in patients with serum endocan level greater than 620 (p = 0.016. There was no difference between groups in terms of hypertension, age, Lymphovascular invasion (LVI, extra capsular extension (ECE, body mass index (BMI and White blood cells (WBC, platelet count and plasma endocan level. Conclusion: Plasma endocan levels higher than non metastatic breast cancer. Patients with high plasma endocan levels are short EFS. Further studies would be useful to assess endocan level as a prognostic factor in breast cancer. Keywords: Endothelial cell specific molecule, Breast cancer, Prognosis

  11. [Hormonotherapy for breast cancer prevention: What about women with genetic predisposition to breast cancer?].

    Science.gov (United States)

    Sénéchal, Claire; Reyal, Fabien; Callet, Nasrine; This, Pascale; Noguès, Catherine; Stoppa-Lyonnet, Dominique; Fourme, Emmanuelle

    2016-03-01

    In France, women carrying BRCA1/2 mutation, at an identified high risk of breast cancer are recommended to undergo breast MRI screening. That screening does not however prevent the risk of developing a breast cancer. The only alternative to breast cancer screening available in France is surgical prevention by prophylactic mastectomy. An interesting option for women who wish to reduce their breast cancer risk, but are unready for prophylactic mastectomy is a preventive hormonal treatment by aromatase inhibitors, or selective estrogens receptor modulators (SERMs). Reliable clinical trials show the efficiency of tamoxifen, raloxifen, exemestane, and anastrozole especially, in reducing breast cancer incidence by 33%, 34%, 65% and 53% respectively. This article tries to sum up the main published trials of breast cancer prevention with hormonal treatment, and presents the latest American and English clinical guidelines concerning hormonal prevention for women at high risk of breast cancer, and starts thinking about the possibilities of hormonoprevention, especially among women carrying a BRCA1/2 mutation in France. Copyright © 2016 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

  12. Metabolic Syndrome and Breast Cancer Risk.

    Science.gov (United States)

    Wani, Burhan; Aziz, Shiekh Aejaz; Ganaie, Mohammad Ashraf; Mir, Mohammad Hussain

    2017-01-01

    The study was meant to estimate the prevalence of metabolic syndrome in patients with breast cancer and to establish its role as an independent risk factor on occurrence of breast cancer. Fifty women aged between 40 and 80 years with breast cancer and fifty controls of similar age were assessed for metabolic syndrome prevalence and breast cancer risk factors, including age at menarche, reproductive status, live births, breastfeeding, and family history of breast cancer, age at diagnosis of breast cancer, body mass index, and metabolic syndrome parameters. Metabolic syndrome prevalence was found in 40.0% of breast cancer patients, and 18.0% of those in control group ( P = 0.02). An independent and positive association was seen between metabolic syndrome and breast cancer risk (odds ratio = 3.037; 95% confidence interval 1.214-7.597). Metabolic syndrome is more prevalent in breast cancer patients and is an independent risk factor for breast cancer.

  13. Immunophenotyping invasive breast cancer: paving the road for molecular imaging

    Directory of Open Access Journals (Sweden)

    Vermeulen Jeroen F

    2012-06-01

    Full Text Available Abstract Background Mammographic population screening in The Netherlands has increased the number of breast cancer patients with small and non-palpable breast tumors. Nevertheless, mammography is not ultimately sensitive and specific for distinct subtypes. Molecular imaging with targeted tracers might increase specificity and sensitivity of detection. Because development of new tracers is labor-intensive and costly, we searched for the smallest panel of tumor membrane markers that would allow detection of the wide spectrum of invasive breast cancers. Methods Tissue microarrays containing 483 invasive breast cancers were stained by immunohistochemistry for a selected set of membrane proteins known to be expressed in breast cancer. Results The combination of highly tumor-specific markers glucose transporter 1 (GLUT1, epidermal growth factor receptor (EGFR, insulin-like growth factor-1 receptor (IGF1-R, human epidermal growth factor receptor 2 (HER2, hepatocyte growth factor receptor (MET, and carbonic anhydrase 9 (CAIX 'detected' 45.5% of tumors, especially basal/triple negative and HER2-driven ductal cancers. Addition of markers with a 2-fold tumor-to-normal ratio increased the detection rate to 98%. Including only markers with >3 fold tumor-to-normal ratio (CD44v6 resulted in an 80% detection rate. The detection rate of the panel containing both tumor-specific and less tumor-specific markers was not dependent on age, tumor grade, tumor size, or lymph node status. Conclusions In search of the minimal panel of targeted probes needed for the highest possible detection rate, we showed that 80% of all breast cancers express at least one of a panel of membrane markers (CD44v6, GLUT1, EGFR, HER2, and IGF1-R that may therefore be suitable for molecular imaging strategies. This study thereby serves as a starting point for further development of a set of antibody-based optical tracers with a high breast cancer detection rate.

  14. Improved detection of breast cancer on FDG-PET cancer screening using breast positioning device

    International Nuclear Information System (INIS)

    Kaida, Hayato; Ishibashi, Masatoshi; Fujii, Teruhiko; Kurata, Seiji; Ogo, Etsuyo; Hayabuchi, Naofumi; Tanaka, Maki

    2008-01-01

    The aim of this study was to investigate the detection rate of breast cancer by positron emission tomography cancer screening using a breast positioning device. Between January 2004 and January 2006, 1,498 healthy asymptomatic individuals underwent cancer screening by fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) at our institution; 660 of 1498 asymptomatic healthy women underwent breast PET imaging in the prone position using the breast positioning device to examine the mammary glands in addition to whole-body PET imaging. All subjects that showed abnormal 18 F-FDG uptake in the mammary glands were referred for further examination or surgery at our institution or a local hospital. Our data were compared with the histopathological findings or findings of other imaging modalities in our institution and replies from the doctors at another hospital. Of the 660 participants, 7 (1.06%) were found to have breast cancers at a curable stage. All the seven cancers were detected by breast PET imaging, but only five of these were detected by whole-body PET imaging; the other two were detected by breast PET imaging using the breast positioning device. In cancer screening, prone breast imaging using a positioning device may help to improve the detection rate of breast cancer. However, overall cancer including mammography and ultrasonography screening should be performed to investigate the false-negative cases and reduce false-positive cases. The effectiveness of prone breast PET imaging in cancer screening should be investigated using a much larger number of cases in the near future. (author)

  15. Effect of BRCA germline mutations on breast cancer prognosis

    Science.gov (United States)

    Baretta, Zora; Mocellin, Simone; Goldin, Elena; Olopade, Olufunmilayo I.; Huo, Dezheng

    2016-01-01

    Abstract Background: The contribution of BRCA germline mutational status to breast cancer patients’ prognosis is unclear. We aimed to systematically review and perform meta-analysis of the available evidence of effects of BRCA germline mutations on multiple survival outcomes of breast cancer patients as a whole and in specific subgroups of interest, including those with triple negative breast cancer, those with Ashkenazi Jewish ancestry, and patients with stage I–III disease. Methods: Sixty studies met all inclusion criteria and were considered for this meta-analysis. These studies involved 105,220 breast cancer patients, whose 3588 (3.4%) were BRCA mutations carriers. The associations between BRCA genes mutational status and overall survival (OS), breast cancer-specific survival (BCSS), recurrence-free survival (RFS), and distant metastasis-free survival (DMFS) were evaluated using random-effect models. Results: BRCA1 mutation carriers have worse OS than BRCA-negative/sporadic cases (hazard ratio, HR 1.30, 95% CI: 1.11–1.52) and worse BCSS than sporadic/BRCA-negative cases among patients with stage I–III breast cancer (HR 1.45, 95% CI: 1.01–2.07). BRCA2 mutation carriers have worse BCSS than sporadic/BRCA-negative cases (HR 1.29, 95% CI: 1.03–1.62), although they have similar OS. Among triple negative breast cancer, BRCA1/2 mutations carriers had better OS than BRCA-negative counterpart (HR 0.49, 95% CI: 0.26–0.92). Among Ashkenazi Jewish women, BRCA1/2 mutations carriers presented higher risk of death from breast cancer (HR 1.44, 95% CI: 1.05–1.97) and of distant metastases (HR 1.82, 95% CI: 1.05–3.16) than sporadic/BRCA-negative patients. Conclusion: Our results support the evaluation of BRCA mutational status in patients with high risk of harboring BRCA germline mutations to better define the prognosis of breast cancer in these patients. PMID:27749552

  16. Targeting glycolysis by 3-bromopyruvate improves tamoxifen cytotoxicity of breast cancer cell lines.

    Science.gov (United States)

    Attia, Yasmin M; El-Abhar, Hanan S; Al Marzabani, Mahmoud M; Shouman, Samia A

    2015-11-03

    Tamoxifen is the standard endocrine therapy for ER+ breast cancer; however, many women still relapse after long-term therapy. 3-Bromopyruvate, a glycolytic inhibitor, has shown high selective anti-tumor activity in vitro, and in vivo. The aim of this study was to evaluate the possible augmentation of the effect of tamoxifen via reprograming cancer cell metabolism using 3-bromopyruvate. An in vitro screening of antitumor activity as well as the apoptotic, anti-metastatic, and anti-angiogenic potentials of the combination therapy were carried out using different techniques on breast cancer cell lines MCF7and T47D. In addition the antitumor effect of the combined therapy was done on mice bearing tumor. Our results showed modulation in apoptosis, angiogenesis and metastatic potential by either drug alone; however, their combination has surpassed that of the individual one. Combination regimen enhanced activated caspases-3, 7 and 9, as well as oxidative stress, signified by increased malondialdehyde and decreased glutathione level. Additionally, the angiogenesis and metastasis markers, including hypoxia inducing factor-1α, vascular endothelia growth factor, and metaloproteinases-2 and 9 were decreased after using the combination regimen. These results were further confirmed by the in vivo study, which depicted a decrease in the tumor volume and angiogenesis and an increase in oxidative stress as well. 3-bromopyruvate could be a valuable compound when added with tamoxifen in breast cancer treatment.

  17. Targeting glycolysis by 3-bromopyruvate improves tamoxifen cytotoxicity of breast cancer cell lines

    International Nuclear Information System (INIS)

    Attia, Yasmin M.; EL-Abhar, Hanan S.; Al Marzabani, Mahmoud M.; Shouman, Samia A.

    2015-01-01

    Tamoxifen is the standard endocrine therapy for ER+ breast cancer; however, many women still relapse after long-term therapy. 3-Bromopyruvate, a glycolytic inhibitor, has shown high selective anti-tumor activity in vitro, and in vivo. The aim of this study was to evaluate the possible augmentation of the effect of tamoxifen via reprograming cancer cell metabolism using 3-bromopyruvate. An in vitro screening of antitumor activity as well as the apoptotic, anti-metastatic, and anti-angiogenic potentials of the combination therapy were carried out using different techniques on breast cancer cell lines MCF7and T47D. In addition the antitumor effect of the combined therapy was done on mice bearing tumor. Our results showed modulation in apoptosis, angiogenesis and metastatic potential by either drug alone; however, their combination has surpassed that of the individual one. Combination regimen enhanced activated caspases-3, 7 and 9, as well as oxidative stress, signified by increased malondialdehyde and decreased glutathione level. Additionally, the angiogenesis and metastasis markers, including hypoxia inducing factor-1α, vascular endothelia growth factor, and metaloproteinases-2 and 9 were decreased after using the combination regimen. These results were further confirmed by the in vivo study, which depicted a decrease in the tumor volume and angiogenesis and an increase in oxidative stress as well. 3-bromopyruvate could be a valuable compound when added with tamoxifen in breast cancer treatment

  18. Carbon Nanomaterials for Breast Cancer Treatment

    Directory of Open Access Journals (Sweden)

    M. L. Casais-Molina

    2018-01-01

    Full Text Available Currently, breast cancer is considered as a health problem worldwide. Furthermore, current treatments neither are capable of stopping its propagation and/or recurrence nor are specific for cancer cells. Therefore, side effects on healthy tissues and cells are common. An increase in the efficiency of treatments, along with a reduction in their toxicity, is desirable to improve the life quality of patients affected by breast cancer. Nanotechnology offers new alternatives for the design and synthesis of nanomaterials that can be used in the identification, diagnosis, and treatment of cancer and has now become a very promising tool for its use against this disease. Among the wide variety of nanomaterials, the scientific community is particularly interested in carbon nanomaterials (fullerenes, nanotubes, and graphene due to their physical properties, versatile chemical functionalization, and biocompatibility. Recent scientific evidence shows the potential uses of carbon nanomaterials as therapeutic agents, systems for selective and controlled drug release, and contrast agents for diagnosing and locating tumors. This generates new possibilities for the development of innovative systems to treat breast cancer and can be used to detect this disease at much earlier stages. Thus, applications of carbon nanomaterials in breast cancer treatment are discussed in this article.

  19. Early Diagnosis of Breast Cancer.

    Science.gov (United States)

    Wang, Lulu

    2017-07-05

    Early-stage cancer detection could reduce breast cancer death rates significantly in the long-term. The most critical point for best prognosis is to identify early-stage cancer cells. Investigators have studied many breast diagnostic approaches, including mammography, magnetic resonance imaging, ultrasound, computerized tomography, positron emission tomography and biopsy. However, these techniques have some limitations such as being expensive, time consuming and not suitable for young women. Developing a high-sensitive and rapid early-stage breast cancer diagnostic method is urgent. In recent years, investigators have paid their attention in the development of biosensors to detect breast cancer using different biomarkers. Apart from biosensors and biomarkers, microwave imaging techniques have also been intensely studied as a promising diagnostic tool for rapid and cost-effective early-stage breast cancer detection. This paper aims to provide an overview on recent important achievements in breast screening methods (particularly on microwave imaging) and breast biomarkers along with biosensors for rapidly diagnosing breast cancer.

  20. Nanodiamonds-mediated doxorubicin nuclear delivery to inhibit lung metastasis of breast cancer.

    Science.gov (United States)

    Xiao, Jisheng; Duan, Xiaopin; Yin, Qi; Zhang, Zhiwen; Yu, Haijun; Li, Yaping

    2013-12-01

    Lung metastasis is one of the greatest challenges for breast cancer treatment. Here, a nanodiamonds (NDs)-mediated doxorubicin (DOX) delivery system was first designed to inhibit the lung metastasis of breast cancer effectively. DOX was non-covalently bound to NDs via physical adsorption in an aqueous solution, then DSPE-PEG 2K was coated to the NDs-DOX complex (NDX) to increase the dispersibility and prolong the circulation time. DSPE-PEG 2K coating NDX (DNX) displayed high drug loading and excellent ability to deliver DOX to the nucleus, thereby significantly enhancing cytotoxicity and inducing cell apoptosis. Furthermore, DNX showed good histocompatibility and could improve drug accumulation in lung, as a result, markedly inhibited the lung metastasis of breast cancer. The high anti-metastasis efficacy with the decreased systemic toxicity suggested that DNX could be a promising drug delivery system for the therapy of lung metastasis of breast cancer. Copyright © 2013 Elsevier Ltd. All rights reserved.

  1. Opioids and breast cancer recurrence

    DEFF Research Database (Denmark)

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

    2015-01-01

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

  2. Breast cancer screening effect across breast density strata: A case-control study.

    Science.gov (United States)

    van der Waal, Daniëlle; Ripping, Theodora M; Verbeek, André L M; Broeders, Mireille J M

    2017-01-01

    Breast cancer screening is known to reduce breast cancer mortality. A high breast density may affect this reduction. We assessed the effect of screening on breast cancer mortality in women with dense and fatty breasts separately. Analyses were performed within the Nijmegen (Dutch) screening programme (1975-2008), which invites women (aged 50-74 years) biennially. Performance measures were determined. Furthermore, a case-control study was performed for women having dense and women having fatty breasts. Breast density was assessed visually with a dichotomized Wolfe scale. Breast density data were available for cases. The prevalence of dense breasts among controls was estimated with age-specific rates from the general population. Sensitivity analyses were performed on these estimates. Screening performance was better in the fatty than in the dense group (sensitivity 75.7% vs 57.8%). The mortality reduction appeared to be smaller for women with dense breasts, with an odds ratio (OR) of 0.87 (95% CI 0.52-1.45) in the dense and 0.59 (95% CI 0.44-0.79) in the fatty group. We can conclude that high density results in lower screening performance and appears to be associated with a smaller mortality reduction. Breast density is thus a likely candidate for risk-stratified screening. More research is needed on the association between density and screening harms. © 2016 UICC.

  3. Genome-Wide Progesterone Receptor Binding: Cell Type-Specific and Shared Mechanisms in T47D Breast Cancer Cells and Primary Leiomyoma Cells

    Science.gov (United States)

    Huang, Lei; Owen, Jonas K.; Xie, Anna; Navarro, Antonia; Monsivais, Diana; Coon V, John S.; Kim, J. Julie; Dai, Yang; Bulun, Serdar E.

    2012-01-01

    Background Progesterone, via its nuclear receptor (PR), exerts an overall tumorigenic effect on both uterine fibroid (leiomyoma) and breast cancer tissues, whereas the antiprogestin RU486 inhibits growth of these tissues through an unknown mechanism. Here, we determined the interaction between common or cell-specific genome-wide binding sites of PR and mRNA expression in RU486-treated uterine leiomyoma and breast cancer cells. Principal Findings ChIP-sequencing revealed 31,457 and 7,034 PR-binding sites in breast cancer and uterine leiomyoma cells, respectively; 1,035 sites overlapped in both cell types. Based on the chromatin-PR interaction in both cell types, we statistically refined the consensus progesterone response element to G•ACA• • •TGT•C. We identified two striking differences between uterine leiomyoma and breast cancer cells. First, the cis-regulatory elements for HSF, TEF-1, and C/EBPα and β were statistically enriched at genomic RU486/PR-targets in uterine leiomyoma, whereas E2F, FOXO1, FOXA1, and FOXF sites were preferentially enriched in breast cancer cells. Second, 51.5% of RU486-regulated genes in breast cancer cells but only 6.6% of RU486-regulated genes in uterine leiomyoma cells contained a PR-binding site within 5 kb from their transcription start sites (TSSs), whereas 75.4% of RU486-regulated genes contained a PR-binding site farther than 50 kb from their TSSs in uterine leiomyoma cells. RU486 regulated only seven mRNAs in both cell types. Among these, adipophilin (PLIN2), a pro-differentiation gene, was induced via RU486 and PR via the same regulatory region in both cell types. Conclusions Our studies have identified molecular components in a RU486/PR-controlled gene network involved in the regulation of cell growth, cell migration, and extracellular matrix function. Tissue-specific and common patterns of genome-wide PR binding and gene regulation may determine the therapeutic effects of antiprogestins in uterine fibroids and

  4. A Phase 1 trial of the PARP inhibitor olaparib (AZD2281) in combination with the anti-angiogenic cediranib (AZD2171) in recurrent epithelial ovarian or triple-negative breast cancer

    Science.gov (United States)

    Liu, Joyce F.; Tolaney, Sara M.; Birrer, Michael; Fleming, Gini F.; Buss, Mary K.; Dahlberg, Suzanne E.; Lee, Hang; Whalen, Christin; Tyburski, Karin; Winer, Eric; Ivy, Percy; Matulonis, Ursula A.

    2014-01-01

    Background PARP-inhibitors and anti-angiogenics have activity in recurrent ovarian and breast cancer; however, the effect of combined therapy against PARP and angiogenesis in this population has not been reported. We investigated the toxicities and recommended phase 2 dosing (RP2D) of the combination of cediranib, a multitargeted inhibitor of VEGFR-1/2/3, and olaparib, a PARP-inhibitor (NCT01116648). Methods Cediranib tablets once daily and olaparib capsules twice daily were administered orally in a standard 3+3 dose escalation design. Patients with recurrent ovarian or metastatic triple-negative breast cancer were eligible. Patients had measurable disease by RECIST 1.1 or met GCIG CA125 criteria. No prior PARP-inhibitors or anti-angiogenics in the recurrent setting were allowed. Results 28 patients (20 ovarian, 8 breast) enrolled to 4 dose levels. 2 DLTs (1 grade 4 neutropenia ≥4 days; 1 grade 4 thrombocytopenia) occurred at the highest dose level (cediranib 30mg daily; olaparib 400mg BID). The RP2D was cediranib 30mg daily and olaparib 200mg BID. Grade 3 or higher toxicities occurred in 75% of patients, and included grade 3 hypertension (25%) and grade 3 fatigue (18%). One grade 3 bowel obstruction occurred. The overall response rate (ORR) in the 18 RECIST-evaluable ovarian cancer patients was 44%, with a clinical benefit rate (ORR plus SD >24 weeks) of 61%. None of the 7 evaluable breast cancer patients achieved clinical response; 2 patients had stable disease for >24 weeks. Interpretation The combination of cediranib and olaparib has hematologic DLTs and anticipated class toxicities, with promising evidence of activity in ovarian cancer patients. PMID:23810467

  5. Beliefs and perceptions about the causes of breast cancer: a case-control study.

    Science.gov (United States)

    Thomson, Allyson K; Heyworth, Jane S; Girschik, Jennifer; Slevin, Terry; Saunders, Christobel; Fritschi, Lin

    2014-08-21

    Attributions of causality are common for many diseases, including breast cancer. The risk of developing breast cancer can be reduced by modifications to lifestyle and behaviours to minimise exposure to specific risk factors, such as obesity. However, these modifications will only occur if women believe that certain behaviours/lifestyle factors have an impact on the development of breast cancer. The Breast Cancer, Environment and Employment Study is a case-control study of breast cancer conducted in Western Australia between 2009 and 2011. As part of the study 1109 women with breast cancer and 1633 women without the disease completed a Risk Perception Questionnaire in which they were asked in an open-ended question for specific cause/s to the development of breast cancer in themselves or in others. The study identified specific causal beliefs, and assessed differences in the beliefs between women with and without breast cancer. The most common attributions in women without breast cancer were to familial or inherited factors (77.6%), followed by lifestyle factors, such as poor diet and smoking (47.1%), and environmental factors, such as food additives (45.4%). The most common attributions in women with breast cancer were to mental or emotional factors (46.3%), especially stress, followed by lifestyle factors (38.6%) and physiological factors (37.5%), particularly relating to hormonal history. While the majority of participants in this study provided one or more causal attributions for breast cancer, many of the reported risk factors do not correspond to those generally accepted by the scientific community. These misperceptions could be having a significant impact on the success of prevention and early detection programs that seek to minimise the pain and suffering caused by this disease. In particular, women who have no family history of the disease may not work to minimise their exposure to the modifiable risk factors.

  6. Breast cancer screening with digital breast tomosynthesis.

    Science.gov (United States)

    Skaane, Per

    2017-01-01

    To give an overview of studies comparing full-field digital mammography (FFDM) and digital breast tomosynthesis (DBT) in breast cancer screening. The implementation of tomosynthesis in breast imaging is rapidly increasing world-wide. Experimental clinical studies of relevance for DBT screening have shown that tomosynthesis might have a great potential in breast cancer screening, although most of these retrospective reading studies are based on small populations, so that final conclusions are difficult to draw from individual reports. Several retrospective studies and three prospective trials on tomosynthesis in breast cancer screening have been published so far, confirming the great potential of DBT in mammography screening. The main results of these screening studies are presented. The retrospective screening studies from USA have all shown a significant decrease in the recall rate using DBT as adjunct to mammography. Most of these studies have also shown an increase in the cancer detection rate, and the non-significant results in some studies might be explained by a lack of statistical power. All the three prospective European trials have shown a significant increase in the cancer detection rate. The retrospective and the prospective screening studies comparing FFDM and DBT have all demonstrated that tomosynthesis has a great potential for improving breast cancer screening. DBT should be regarded as a better mammogram that could improve or overcome limitations of the conventional mammography, and tomosynthesis might be considered as the new technique in the next future of breast cancer screening.

  7. LGR4 modulates breast cancer initiation, metastasis, and cancer stem cells.

    Science.gov (United States)

    Yue, Zhiying; Yuan, Zengjin; Zeng, Li; Wang, Ying; Lai, Li; Li, Jing; Sun, Peng; Xue, Xiwen; Qi, Junyi; Yang, Zhengfeng; Zheng, Yansen; Fang, Yuanzhang; Li, Dali; Siwko, Stefan; Li, Yi; Luo, Jian; Liu, Mingyao

    2018-05-01

    The fourth member of the leucine-rich repeat-containing GPCR family (LGR4, frequently referred to as GPR48) and its cognate ligands, R-spondins (RSPOs) play crucial roles in the development of multiple organs as well as the survival of adult stem cells by activation of canonical Wnt signaling. Wnt/β-catenin signaling acts to regulate breast cancer; however, the molecular mechanisms determining its spatiotemporal regulation are largely unknown. In this study, we identified LGR4 as a master controller of Wnt/β-catenin signaling-mediated breast cancer tumorigenesis, metastasis, and cancer stem cell (CSC) maintenance. LGR4 expression in breast tumors correlated with poor prognosis. Either Lgr4 haploinsufficiency or mammary-specific deletion inhibited mouse mammary tumor virus (MMTV)- PyMT- and MMTV- Wnt1-driven mammary tumorigenesis and metastasis. Moreover, LGR4 down-regulation decreased in vitro migration and in vivo xenograft tumor growth and lung metastasis. Furthermore, Lgr4 deletion in MMTV- Wnt1 tumor cells or knockdown in human breast cancer cells decreased the number of functional CSCs by ∼90%. Canonical Wnt signaling was impaired in LGR4-deficient breast cancer cells, and LGR4 knockdown resulted in increased E-cadherin and decreased expression of N-cadherin and snail transcription factor -2 ( SNAI2) (also called SLUG), implicating LGR4 in regulation of epithelial-mesenchymal transition. Our findings support a crucial role of the Wnt signaling component LGR4 in breast cancer initiation, metastasis, and breast CSCs.-Yue, Z., Yuan, Z., Zeng, L., Wang, Y., Lai, L., Li, J., Sun, P., Xue, X., Qi, J., Yang, Z., Zheng, Y., Fang, Y., Li, D., Siwko, S., Li, Y., Luo, J., Liu, M. LGR4 modulates breast cancer initiation, metastasis, and cancer stem cells.

  8. The Antimetastatic and Antiangiogenesis Effects of Kefir Water on Murine Breast Cancer Cells.

    Science.gov (United States)

    Zamberi, Nur Rizi; Abu, Nadiah; Mohamed, Nurul Elyani; Nordin, Noraini; Keong, Yeap Swee; Beh, Boon Kee; Zakaria, Zuki Abu Bakar; Nik Abdul Rahman, Nik Mohd Afizan; Alitheen, Noorjahan Banu

    2016-12-01

    Kefir is a unique cultured product that contains beneficial probiotics. Kefir culture from other parts of the world exhibits numerous beneficial qualities such as anti-inflammatory, immunomodulation, and anticancer effects. Nevertheless, kefir cultures from different parts of the world exert different effects because of variation in culture conditions and media. Breast cancer is the leading cancer in women, and metastasis is the major cause of death associated with breast cancer. The antimetastatic and antiangiogenic effects of kefir water made from kefir grains cultured in Malaysia were studied in 4T1 breast cancer cells. 4T1 cancer cells were treated with kefir water in vitro to assess its antimigration and anti-invasion effects. BALB/c mice were injected with 4T1 cancer cells and treated orally with kefir water for 28 days. Kefir water was cytotoxic toward 4T1 cells at IC 50 (half-maximal inhibitory concentration) of 12.5 and 8.33 mg/mL for 48 and 72 hours, respectively. A significant reduction in tumor size and weight (0.9132 ± 0.219 g) and a substantial increase in helper T cells (5-fold) and cytotoxic T cells (7-fold) were observed in the kefir water-treated group. Proinflammatory and proangiogenic markers were significantly reduced in the kefir water-treated group. Kefir water inhibited tumor proliferation in vitro and in vivo mainly through cancer cell apoptosis, immunomodulation by stimulating T helper cells and cytotoxic T cells, and anti-inflammatory, antimetastatic, and antiangiogenesis effects. This study brought out the potential of the probiotic beverage kefir water in cancer treatment. © The Author(s) 2016.

  9. New castanospermine glycoside analogues inhibit breast cancer cell proliferation and induce apoptosis without affecting normal cells.

    Directory of Open Access Journals (Sweden)

    Ghada Allan

    Full Text Available sp²-Iminosugar-type castanospermine analogues have been shown to exhibit anti-tumor activity. However, their effects on cell proliferation and apoptosis and the molecular mechanism at play are not fully understood. Here, we investigated the effect of two representatives, namely the pseudo-S- and C-octyl glycoside 2-oxa-3-oxocastanospermine derivatives SO-OCS and CO-OCS, on MCF-7 and MDA-MB-231 breast cancer and MCF-10A mammary normal cell lines. We found that SO-OCS and CO-OCS inhibited breast cancer cell viability in a concentration- and time-dependent manner. This effect is specific to breast cancer cells as both molecules had no impact on normal MCF-10A cell proliferation. Both drugs induced a cell cycle arrest. CO-OCS arrested cell cycle at G1 and G2/M in MCF-7 and MDA-MB-231 cells respectively. In MCF-7 cells, the G1 arrest is associated with a reduction of CDK4 (cyclin-dependent kinase 4, cyclin D1 and cyclin E expression, pRb phosphorylation, and an overexpression of p21(Waf1/Cip1. In MDA-MB-231 cells, CO-OCS reduced CDK1 but not cyclin B1 expression. SO-OCS accumulated cells in G2/M in both cell lines and this blockade was accompanied by a decrease of CDK1, but not cyclin B1 expression. Furthermore, both drugs induced apoptosis as demonstrated by the increased percentage of annexin V positive cells and Bax/Bcl-2 ratio. Interestingly, in normal MCF-10A cells the two drugs failed to modify cell proliferation, cell cycle progression, cyclins, or CDKs expression. These results demonstrate that the effect of CO-OCS and SO-OCS is triggered by both cell cycle arrest and apoptosis, suggesting that these castanospermine analogues may constitute potential anti-cancer agents against breast cancer.

  10. The Paradox of Oestradiol-Induced Breast Cancer Cell Growth and Apoptosis.

    Science.gov (United States)

    Maximov, Philipp Y; Lewis-Wambi, Joan S; Jordan, V Craig

    2009-05-01

    High dose oestrogen therapy was used as a treatment for postmenopausal patients with breast cancer from the 1950s until the introduction of the safer antioestrogen, tamoxifen in the 1970s. The anti-tumour mechanism of high dose oestrogen therapy remained unknown. There was no enthusiasm to study these signal transduction pathways as oestrogen therapy has almost completely been eliminated from the treatment paradigm. Current use of tamoxifen and the aromatase inhibitors seek to create oestrogen deprivation that prevents the growth of oestrogen stimulated oestrogen receptor (ER) positive breast cancer cells. However, acquired resistance to antihormonal therapy does occur, but it is through investigation of laboratory models that a vulnerability of the cancer cell has been discovered and is being investigated to provide new opportunities in therapy with the potential for discovering new cancer-specific apoptotic drugs. Laboratory models of resistance to raloxifene and tamoxifen, the selective oestrogen receptor modulators (SERMs) and aromatase inhibitors demonstrate an evolution of drug resistance so that after many years of oestrogen deprivation, the ER positive cancer cell reconfigures the survival signal transduction pathways so oestrogen now becomes an apoptotic trigger rather than a survival signal. Current efforts are evaluating the mechanisms of oestrogen-induced apoptosis and how this new biology of oestrogen action can be amplified and enhanced, thereby increasing the value of this therapeutic opportunity for the treatment of breast cancer. Several synergistic approaches to therapeutic enhancement are being advanced which involve drug combinations to impair survival signaling with the use of specific agents and to impair bcl-2 that protects the cancer cell from apoptosis. We highlight the historical understanding of oestrogen's role in cell survival and death and specifically illustrate the progress that has been made in the last five years to understand the

  11. PPARgamma-PGC-1alpha activity is determinant of alcohol related breast cancer

    DEFF Research Database (Denmark)

    Koefoed Petersen, Rasmus; Benzon Larsen, Signe; Jensen, Ditte Marie

    2012-01-01

    Alcohol is a risk factor for postmenopausal breast cancer. One of several proposed mechanisms is that alcohol-related breast cancer is caused by increased sex hormone levels. PPARγ inhibits aromatase transcription in breast adipocytes. We reproduced previously found allele-specific effects...... of the wildtype Pro-allele of PPARG Pro12Ala in alcohol related breast cancer. In transiently transfected cells, transcriptional activation by PPARγ and the PPARγ-PGC-1α complex was inhibited by ethanol. PPARγ 12Ala-mediated transcription activation was not enhanced by PGC-1α, resulting in allele......-specific transcription activation by the PPARγ 12Pro-PGC-1α complex. Our results suggest that PPARγ and PGC-1α activity is an important determinant of alcohol related breast cancer....

  12. Trends in breast cancer incidence among women with type-2 diabetes in British general practice

    DEFF Research Database (Denmark)

    Bronsveld, Heleen K; Peeters, Paul J H L; de Groot, Mark C H

    2017-01-01

    Aims: To quantify breast cancer incidence in women with type-2 diabetes and assess age-standardized trends in invasive breast cancer incidence over time and by age groups. Methods: A population-based cohort study was conducted using the British general practice database (Clinical Practice Research...... Datalink) using data from 1989 to 2012. All adult women prescribed anti-hyperglycemic medication were selected and matched (1:1) on age and clinical practice to a reference cohort without diabetes. Results: During approximately 1.6 million person years (py), 2371 breast cancer cases were diagnosed...... that observed in the reference cohort (148, 95%CI:141-156); with an incidence rate ratio (IRR) of 1.01 (95%CI:0.94-1.08, p. >. 0.05). Conclusions: Currently, around 2880 women with type-2 diabetes are diagnosed with breast cancer per year in the United Kingdom. However, breast cancer incidence remained stable...

  13. DIAGNOSTIC AND PROGNOSTIC UTILITY OF SERUM PSA IN BREAST CANCER

    Institute of Scientific and Technical Information of China (English)

    张淑群; 强水云; 李妙羡; 纪宗正

    2004-01-01

    Objective To investigate the diagnostic and prognostic value of total and free prostate-specific antigen (PSA) in breast cancer women. Methods Using the microparticle enzyme immunoassay system, we measured the concentrations of these markers in the sera of 85 women with breast cancer and in 30 healthy women.Results Free PSA levels were significantly higher in women with breast cancer than healthy women (P <0. 05 ).The percentage of free PSA predominant subjects was 37. 6% in breast cancer patients and 3. 3% in healthy women.In women with breast cancer,total PSA positivity was 23.5% and free PSA positivity was 27. 1%. When compared to negatives,total PSA positive patients had a higher percentage of lymph node involvement tamours ( P >0. 05).However, patients with predominant free PSA had a higher percentage of early stage than patients with predominant PSA-ACT. Conclusion This study indicate clinical significance of preoperative measurement of serum total and free PSA in diagnosis and prognosis of women with breast cancer. The expression of KLKs is correlated with carcinogenesis of breast cancer.

  14. Novel Growth Factor as Prognostic Marker for Estrogen-Independence in Breast Cancer

    National Research Council Canada - National Science Library

    Serrero, Ginette

    2002-01-01

    ...-independence and tamoxifen resistance. Here, wave conducted a study with 206 paraffin embedded human breast cancer biopsies and measured PCDGF expression by immunohistochemistry using an anti-PCDGF developed in our laboratory...

  15. 'Tablet burden' in patients with metastatic breast cancer.

    Science.gov (United States)

    Milic, Marina; Foster, Anna; Rihawi, Karim; Anthoney, Alan; Twelves, Chris

    2016-03-01

    The implications for patients with cancer, of the 'tablet burden' resulting from increasing use of oral anticancer drugs and medication for co-morbidities have not previously been well explored. We sought to (i) quantify tablet burden in women with metastatic breast cancer (MBC), (ii) establish which groups of drug contribute most to this burden and (iii) gain insight into patients' attitudes towards oral anti-cancer treatment. One hundred patients with MBC anonymously completed a questionnaire describing their medication histories and attitudes towards their tablets. The patients (mean age 60, range 31-95) were all female and taking a median of six tablets (range 0-31) daily; 37 patients were taking >10 tablets. Oral anticancer treatment constituted the category of treatment taken by the highest proportion of patients, followed by symptomatic cancer treatments, proton pump inhibitors and cardiovascular medication. Numerically, however, symptomatic drugs accounted for 44% of all tablets and specific anti-cancer treatment for 15%; medication not directly related to the cancer accounted for the remaining 40% of tablets. A quarter of patients reported inconvenience in taking their tablets, the main reason being tablet size and one third reported forgetting their tablets at least once a week. Nearly two thirds of patients expressing a preference favoured oral anticancer treatment, the commonest reason being greater convenience. Tablet burden is considerable for many patients with MBC and can be problematic. A significant proportion of tablets represent treatment for co-morbidities, the significance of which may be questionable in women with MBC. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Marital status and optimism score among breast cancer survivors.

    Science.gov (United States)

    Croft, Lindsay; Sorkin, John; Gallicchio, Lisa

    2014-11-01

    There are an increasing number of breast cancer survivors, but their psychosocial and supportive care needs are not well-understood. Recent work has found marital status, social support, and optimism to be associated with quality of life, but little research has been conducted to understand how these factors relate to one another. Survey data from 722 breast cancer survivors were analyzed to estimate the association between marital status and optimism score, as measured using the Life Orientation Test-Revised. Linear regression was used to estimate the relationship of marital status and optimism, controlling for potential confounding variables and assessing effect modification. The results showed that the association between marital status and optimism was modified by time since breast cancer diagnosis. Specifically, in those most recently diagnosed (within 5 years), married breast cancer survivors had a 1.50 higher mean optimism score than unmarried survivors (95 % confidence interval (CI) 0.37, 2.62; p = 0.009). The difference in optimism score by marital status was not present more than 5 years from breast cancer diagnosis. Findings suggest that among breast cancer survivors within 5 years since diagnosis, those who are married have higher optimism scores than their unmarried counterparts; this association was not observed among longer-term breast cancer survivors. Future research should examine whether the difference in optimism score among this subgroup of breast cancer survivors is clinically relevant.

  17. Relevance of health economics in breast cancer treatment: integration of economics in the management of breast cancer at the clinic level.

    Science.gov (United States)

    Jacobs, Volker R; Bogner, Gerhard; Schausberger, Christiane E; Reitsamer, Roland; Fischer, Thorsten

    2013-03-01

    Since the introduction of the diagnosis-related groups (DRG) system with cost-related and entity-specific flat-rate reimbursements for all in-patients in 2004 in Germany, economics have become an important focus in medical care, including breast centers. Since then, physicians and hospitals have had to gradually take on more and more financial responsibilities for their medical care to avoid losses for their institutions. Due to financial limitations of resources, most medical services have to be adjusted to correlating revenues, which results in the development of a variety of active measures to understand, steer, and optimize costs, resources and related processes for breast cancer treatment. In this review, the challenging task to implement microeconomic management at the clinic level for breast cancer treatment is analyzed from breast cancer-specific publications. The newly developed economic management perspective is identified for different stakeholders in the healthcare system, and successful microeconomic projects and future aspects are described.

  18. Identifying cost-effective treatment with raloxifene in postmenopausal women using risk algorithms for fractures and invasive breast cancer.

    Science.gov (United States)

    Ivergård, M; Ström, O; Borgström, F; Burge, R T; Tosteson, A N A; Kanis, J

    2010-11-01

    The National Osteoporosis Foundation (NOF) recommends considering treatment in women with a 20% or higher 10-year probability of a major fracture. However, raloxifene reduces both the risk of vertebral fractures and invasive breast cancer so that raloxifene treatment may be clinically appropriate and cost-effective in women who do not meet a 20% threshold risk. The aim of this study was to identify cost-effective scenarios of raloxifene treatment compared to no treatment in younger postmenopausal women at increased risk of invasive breast cancer and fracture risks below 20%. A micro-simulation model populated with data specific to American Caucasian women was used to quantify the costs and benefits of 5-year raloxifene treatment. The population evaluated was selected based on 10-year major fracture probability as estimated with FRAX® being below 20% and 5-year invasive breast cancer risk as estimated with the Gail risk model ranging from 1% to 5%. The cost per QALY gained ranged from US $22,000 in women age 55 with 5% invasive breast cancer risk and 15-19.9% fracture probability, to $110,000 in women age 55 with 1% invasive breast cancer risk and 5-9.9% fracture probability. Raloxifene was progressively cost-effective with increasing fracture risk and invasive breast cancer risk for a given age cohort. At lower fracture risk in combination with lower invasive breast cancer risk or when no preventive raloxifene effect on invasive breast cancer was assumed, the cost-effectiveness of raloxifene worsened markedly and was not cost-effective given a willingness-to-pay of US $50,000. At fracture risk of 15-19.9% raloxifene was cost-effective also in women at lower invasive breast cancer risk. Raloxifene is potentially cost-effective in cohorts of young postmenopausal women, who do not meet the suggested NOF 10-year fracture risk threshold. The cost-effectiveness is contingent on their 5-year invasive breast cancer risk. The result highlights the importance of considering

  19. Breast Cancer Rates by State

    Science.gov (United States)

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

  20. In Vivo Detection of HSP90 Identifies Breast Cancers with Aggressive Behavior.

    Science.gov (United States)

    Osada, Takuya; Kaneko, Kensuke; Gwin, William R; Morse, Michael A; Hobeika, Amy; Pogue, Brian W; Hartman, Zachary C; Hughes, Philip F; Haystead, Timothy; Lyerly, H Kim

    2017-12-15

    Purpose: Hsp90, a chaperone to numerous molecular pathways in malignant cells, is elevated in aggressive breast cancers. We hypothesized that identifying breast cells with elevated Hsp90 activity in situ could result in early detection of aggressive breast cancers. Experimental Design: We exploited the uptake of an Hsp90 inhibitor by malignant cells to create an imaging probe (HS131) of Hsp90 activity by linking it to a near-infrared (nIR) dye. HS131 uptake into cells correlated with cell membrane expression of Hsp90 and was used to image molecular subtypes of murine and human breast cancers in vitro and in murine models. Results: HS131 imaging was both sensitive and specific in detecting the murine 4T1 breast cancer cell line, as well as subclones with differing metastatic potential. Highly metastatic subclones (4T07) had high HS131 uptake, but subclones with lower metastatic potential (67NR, 168FARN) had low HS131 uptake. We generated isogenic cell lines to demonstrate that overexpression of a variety of specific oncogenes resulted in high HS131 uptake and retention. Finally, we demonstrated that HS131 could be used to detect spontaneous tumors in MMTV-neu mice, as well as primary and metastatic human breast cancer xenografts. HS131 could image invasive lobular breast cancer, a histologic subtype of breast cancer which is often undetectable by mammography. Conclusions: An HSP90-targeting nIR probe is sensitive and specific in imaging all molecular subtypes of murine and human breast cancer, with higher uptake in aggressive and highly metastatic clones. Clinical studies with Hsp90-targeting nIR probes will be initiated shortly. Clin Cancer Res; 23(24); 7531-42. ©2017 AACR . ©2017 American Association for Cancer Research.

  1. GATA3 expression in advanced breast cancer: prognostic value and organ-specific relapse.

    Science.gov (United States)

    McCleskey, Brandi C; Penedo, Thuy L; Zhang, Kui; Hameed, Omar; Siegal, Gene P; Wei, Shi

    2015-11-01

    GATA3 is a transcription factor regulating luminal cell differentiation in the mammary glands and has been implicated in the luminal types of breast carcinoma. The prognostic significance of GATA3 in breast cancer remains controversial. In this study, we assessed the prognostic value of the molecule in a subset of 62 advanced breast cancers and 10 control breast cancers (no metastasis after follow-up). GATA3 expression levels in luminal tumors of advanced stage were significantly higher than that of the human epidermal growth factor receptor 2 (HER2) subtype and triple-negative carcinomas, as expected, but were similar to those of the luminal controls. Furthermore, 88% of nonluminal tumors showed variable GATA3 expression, for which the HER2 subtype had significantly higher GATA3 expression than that of the triple-negative carcinomas. Interestingly, GATA3 levels were significantly lower in carcinomas with lung relapse compared to those with metastatic recurrence to other organs, thus reflecting the findings in animal models. No significant difference was observed between tumors with bone relapse and those metastasized to nonskeletal sites. Moreover, high GATA3 expression was significantly associated with favorable relapse-free survival and overall survival. These findings suggest that GATA3 may not act solely as a luminal differentiation marker, and further uncovering the molecular pathways by which GATA3 regulates the downstream targets will be crucial to our understanding of breast cancer dissemination. Copyright© by the American Society for Clinical Pathology.

  2. Specific repression of mutant K-RAS by 10-23 DNAzyme: Sensitizing cancer cell to anti-cancer therapies

    International Nuclear Information System (INIS)

    Yu, S.-H.; Wang, T.-H.; Au, L.-C.

    2009-01-01

    Point mutations of the Ras family are frequently found in human cancers at a prevalence rate of 30%. The most common mutation K-Ras(G12V), required for tumor proliferation, survival, and metastasis due to its constitutively active GTPase activity, has provided an ideal target for cancer therapy. 10-23 DNAzyme, an oligodeoxyribonucleotide-based ribonuclease consisting of a 15-nucleotide catalytical domain flanked by two target-specific complementary arms, has been shown to effectively cleave the target mRNA at purine-pyrimidine dinucleotide. Taking advantage of this specific property, 10-23 DNAzyme was designed to cleave mRNA of K-Ras(G12V)(GGU → GUU) at the GU dinucleotide while left the wild-type (WT) K-Ras mRNA intact. The K-Ras(G12V)-specific 10-23 DNAzyme was able to reduce K-Ras(G12V) at both mRNA and protein levels in SW480 cell carrying homozygous K-Ras(G12V). No effect was observed on the WT K-Ras in HEK cells. Although K-Ras(G12V)-specific DNAzymes alone did not inhibit proliferation of SW480 or HEK cells, pre-treatment of this DNAzyme sensitized the K-Ras(G12V) mutant cells to anti-cancer agents such as doxorubicin and radiation. These results offer a potential of using allele-specific 10-23 DNAzyme in combination with other cancer therapies to achieve better effectiveness on cancer treatment.

  3. Breast Cancer in Men

    Science.gov (United States)

    ... ultrasound or a breast MRI cannot rule out breast cancer then you will need a biopsy to confirm diagnosis. If diagnosed When first diagnosed with breast cancer, many men are in shock. After all, ...

  4. Anti-angiogenic activity in metastasis of human breast cancer cells irradiated by a proton beam

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Kyu-Shik; Shin, Jin-Sun; Nam, Kyung-Soo [Dongguk University, Gyeongju (Korea, Republic of); Shon, Yun-Hee [Kyungpook National University Hospital, Daegu (Korea, Republic of)

    2012-07-15

    Angiogenesis is an essential process of metastasis in human breast cancer. We investigated the effects of proton beam irradiation on angiogenic enzyme activities and their expressions in MCF-7 human breast cancer cells. The regulation of angiogenic regulating factors, of transforming growth factor-β (TGF-β) and of vesicular endothelial growth factor (VEGF) expression in breast cancer cells irradiated with a proton beam was studied. Aromatase activity and mRNA expression, which is correlated with metastasis, were significantly decreased by irradiation with a proton beam in a dose-dependent manner. TGF-β and VEGF transcriptions were also diminished by proton beam irradiation. In contrast, transcription of tissue inhibitors of matrix metalloproteinases (TIMPs), also known as biological inhibitors of matrix metalloproteinases (MMPs), was dose-dependently enhanced. Furthermore, an increase in the expression of TIMPs caused the MMP-9 activity to be diminished and the MMP-9 and the MMP-2 expressions to be decreased. These results suggest that inhibition of angiogenesis by proton beam irradiation in breast cancer cells is closely related to inhibitions of aromatase activity and transcription and to down-regulation of TGF-β and VEGF transcription.

  5. Tumor cells induce the cancer associated fibroblast phenotype via caveolin-1 degradation: implications for breast cancer and DCIS therapy with autophagy inhibitors.

    Science.gov (United States)

    Martinez-Outschoorn, Ubaldo E; Pavlides, Stephanos; Whitaker-Menezes, Diana; Daumer, Kristin M; Milliman, Janet N; Chiavarina, Barbara; Migneco, Gemma; Witkiewicz, Agnieszka K; Martinez-Cantarin, Maria P; Flomenberg, Neal; Howell, Anthony; Pestell, Richard G; Lisanti, Michael P; Sotgia, Federica

    2010-06-15

    Loss of stromal caveolin 1 (Cav-1) is a novel biomarker for cancer-associated fibroblasts that predicts poor clinical outcome in breast cancer and DCIS patients. We hypothesized that epithelial cancer cells may have the ability to drive Cav-1 downregulation in adjacent normal fibroblasts, thereby promoting the cancer associated fibroblast phenotype. To test this hypothesis directly, here we developed a novel co-culture model employing (i) human breast cancer cells (MCF7), and (ii) immortalized fibroblasts (hTERT-BJ1), which are grown under defined experimental conditions. Importantly, we show that co-culture of immortalized human fibroblasts with MCF7 breast cancer cells leads to Cav-1 downregulation in fibroblasts. These results were also validated using primary cultures of normal human mammary fibroblasts co-cultured with MCF7 cells. In this system, we show that Cav-1 downregulation is mediated by autophagic/lysosomal degradation, as pre-treatment with lysosome-specific inhibitors rescues Cav-1 expression. Functionally, we demonstrate that fibroblasts co-cultured with MCF7 breast cancer cells acquire a cancer associated fibroblast phenotype, characterized by Cav-1 downregulation, increased expression of myofibroblast markers and extracellular matrix proteins, and constitutive activation of TGFβ/Smad2 signaling. siRNA-mediated Cav-1 downregulation mimics several key changes that occur in co-cultured fibroblasts, clearly indicating that a loss of Cav-1 is a critical initiating factor, driving stromal fibroblast activation during tumorigenesis. As such, this co-culture system can now be used as an experimental model for generating "synthetic" cancer associated fibroblasts (CAFs). More specifically, these "synthetic" CAFs could be used for drug screening to identify novel therapeutics that selectively target the Cav-1-negative tumor micro-environment. Our findings also suggest that chloroquine, or other autophagy/lysosome inhibitors, may be useful as anti-cancer

  6. Risk of primary non-breast cancer after female breast cancer by age at diagnosis

    DEFF Research Database (Denmark)

    Mellemkjær, Lene; Christensen, Jane; Frederiksen, Kirsten Skovsgaard

    2011-01-01

    Women diagnosed with breast cancer at young age have been shown to be at higher risk of developing a new primary cancer than women diagnosed at older ages, but little is known about whether adjustment for calendar year of breast cancer diagnosis, length of follow-up, and/or breast cancer treatment...

  7. Workplace support after breast cancer treatment: recognition of vulnerability.

    Science.gov (United States)

    Tiedtke, Corine; Dierckx de Casterlé, Bernadette; Donceel, Peter; de Rijk, Angelique

    2015-01-01

    Support from the workplace seems to be a key element in addressing the poor return-to-work (RTW) rate of employees with breast cancer. We aim to acquire an in-depth understanding of how Flemish employees experience their RTW after breast cancer and the support from the workplace. Fourteen in-depth interviews of women who experienced breast cancer and returned to work (high school graduates, age range 42-55 years, mean age 48 at time of surgery) were analysed using the Qualitative Analysis Guide of Leuven (QUAGOL), based on a Grounded Theory approach. The key experiences were feeling vulnerable, feeling able to work and need for support. Although little diversity in RTW experiences was found, the background of the vulnerability varied. Women experienced support (which could be emotional or practical) only as adequate if it addressed their specific vulnerability. Employees felt particularly vulnerable. Vulnerability is not the same as low-work ability and as such it should be added as theoretical concept in RTW research. Adequate workplace support addresses the specific vulnerability of an individual woman. Our study offers a nuanced insight into the RTW process of breast cancer survivors. Upon actual return-to-work (RTW) after breast cancer treatment, women feel vulnerable but able to work and, hence, have a high need for workplace support. Support from the workplace during RTW after breast cancer treatment is experienced as adequate when it expresses genuine recognition of the individual woman's vulnerability.

  8. XIAP over-expression is an independent poor prognostic marker in Middle Eastern breast cancer and can be targeted to induce efficient apoptosis.

    Science.gov (United States)

    Hussain, Azhar R; Siraj, Abdul Khalid; Ahmed, Maqbool; Bu, Rong; Pratheeshkumar, Poyil; Alrashed, Alanood M; Qadri, Zeeshan; Ajarim, Dahish; Al-Dayel, Fouad; Beg, Shaham; Al-Kuraya, Khawla S

    2017-09-11

    Breast cancer is the most common cancer in females and is ranked second in cancer-related deaths all over the world in women. Despite improvement in diagnosis, the survival rate of this disease has still not improved. X-linked Inhibitor of Apoptosis (XIAP) has been shown to be over-expressed in various cancers leading to poor overall survival. However, the role of XIAP in breast cancer from Middle Eastern region has not been fully explored. We examined the expression of XIAP in more than 1000 Middle Eastern breast cancer cases by immunohistochemistry. Apoptosis was measured by flow cytometry. Protein expression was determined by western blotting. Finally, in vivo studies were performed on nude mice following xenografting and treatment with inhibitors. XIAP was found to be over-expressed in 29.5% of cases and directly associated with clinical parameters such as tumor size, extra nodal extension, triple negative breast cancer and poorly differentiated breast cancer subtype. In addition, XIAP over-expression was also significantly associated with PI3-kinase pathway protein; p-AKT, proliferative marker; Ki-67 and anti-apoptotic marker; PARP. XIAP over-expression in our cohort of breast cancer was an independent poor prognostic marker in multivariate analysis. Next, we investigated inhibition of XIAP using a specific inhibitor; embelin and found that embelin treatment led to inhibition of cell viability and induction of apoptosis in breast cancer cells. Finally, breast cancer cells treated with combination of embelin and PI3-kinase inhibitor; LY294002 synergistically induced apoptosis and caused tumor growth regression in vivo. These data suggest that XIAP may be playing an important role in the pathogenesis of breast cancer and can be therapeutically targeted either alone or in combination with PI3-kinase inhibition to induce efficient apoptosis in breast cancer cells.

  9. Problems faced returning to work after cancer: a focus on breast cancer and its specificities

    OpenAIRE

    Asselain, David

    2011-01-01

    Introduction: Life after cancer is one of the major issues of the 2nd "Cancer Plan" in France. In this context, our study aims at analyzing professional consequences of breast cancer, which has a relatively good prognosis and is the most common cancer in the working population. Methods: Medical and professional information about 402 workers from the Paris region who had cancer in 2005/2006 was collected by occupational physicians using a self-administered questionnaire. Multifactorial analysi...

  10. Quercetin Suppresses Twist to Induce Apoptosis in MCF-7 Breast Cancer Cells.

    Directory of Open Access Journals (Sweden)

    Santhalakshmi Ranganathan

    Full Text Available Quercetin is a dietary flavonoid which exerts anti-oxidant, anti-inflammatory and anti-cancer properties. In this study, we investigated the anti-proliferative effect of quercetin in two breast cancer cell lines (MCF-7 and MDA-MB-231, which differed in hormone receptor. IC50 value (37μM of quercetin showed significant cytotoxicity in MCF-7 cells, which was not observed in MDA-MB-231 cells even at 100μM of quercetin treatment. To study the response of cancer cells to quercetin, with respect to different hormone receptors, both the cell lines were treated with a fixed concentration (40μM of quercetin. MCF-7 cells on quercetin treatment showed more apoptotic cells with G1 phase arrest. In addition, quercetin effectively suppressed the expression of CyclinD1, p21, Twist and phospho p38MAPK, which was not observed in MDA-MB-231 cells. To analyse the molecular mechanism of quercetin in exerting an apoptotic effect in MCF-7 cells, Twist was over-expressed and the molecular changes were observed after quercetin administration. Quercetin effectively regulated the expression of Twist, in turn p16 and p21 which induced apoptosis in MCF-7 cells. In conclusion, quercetin induces apoptosis in breast cancer cells through suppression of Twist via p38MAPK pathway.

  11. Epidemiology of radiogenic breast cancer

    International Nuclear Information System (INIS)

    Howe, G.R.

    1984-01-01

    The primary objective of epidemiologic studies of radiogenic breast cancer is to use empirical data from human populations exposed to radiation, in order to delineate increases in risk of breast cancer as a function of the radiation characteristics and the characteristics of the women exposed. In addition, such empirical data may be used to test hypotheses concerning the biological mechanism of radiation-induced breast cancer, and this mechanism in turn may serve as a useful model both for other radiogenic solid tumors, and for breast tumors induced by other carcinogens. Specifically, the objective may be formulated in terms of developing an appropriate relatively simple mathematical model, whose functional form may be tested and whose parameters may be estimated from the relevant human data. It is necessary to derive such a model, both because of the sampling instability of estimates based on small subgroups of populations and also because observations may not be available in populations with the characteristics of interest. These latter two restrictions are exemplified by the problem of estimating an increase in risk for individuals with relatively small exposures, and the problem of estimating lifetime risk

  12. Epigenetic Regulation by Sulforaphane: Opportunities for Breast and Prostate Cancer Chemoprevention.

    Science.gov (United States)

    Atwell, Lauren L; Beaver, Laura M; Shannon, Jackilen; Williams, David E; Dashwood, Roderick H; Ho, Emily

    2015-04-01

    Sulforaphane (SFN) is a phytochemical derived from cruciferous vegetables that has multiple molecular targets and anti-cancer properties. Researchers have demonstrated several chemopreventive benefits of SFN consumption, such as reductions in tumor growth, increases in cancer cell apoptosis, and disruption of signaling within tumor microenvironments both in vitro and in vivo . Emerging evidence indicates that SFN exerts several of its chemopreventive effects by altering epigenetic mechanisms. This review summarizes evidence of the impact of SFN on epigenetic events and how they relate to the chemopreventive effects of SFN observed in preclinical and clinical studies of breast and prostate cancers. Specific areas of focus include the role of SFN in the regulation of cell cycle, apoptosis, inflammation, antioxidant defense, and cancer cell signaling and their relationships to epigenetic mechanisms. Finally, remaining challenges and research needs for translating mechanistic work with SFN into human studies and clinical intervention trials are discussed.

  13. Mammographic density and breast cancer risk in breast screening assessment cases and women with a family history of breast cancer.

    Science.gov (United States)

    Duffy, Stephen W; Morrish, Oliver W E; Allgood, Prue C; Black, Richard; Gillan, Maureen G C; Willsher, Paula; Cooke, Julie; Duncan, Karen A; Michell, Michael J; Dobson, Hilary M; Maroni, Roberta; Lim, Yit Y; Purushothaman, Hema N; Suaris, Tamara; Astley, Susan M; Young, Kenneth C; Tucker, Lorraine; Gilbert, Fiona J

    2018-01-01

    Mammographic density has been shown to be a strong independent predictor of breast cancer and a causative factor in reducing the sensitivity of mammography. There remain questions as to the use of mammographic density information in the context of screening and risk management, and of the association with cancer in populations known to be at increased risk of breast cancer. To assess the association of breast density with presence of cancer by measuring mammographic density visually as a percentage, and with two automated volumetric methods, Quantra™ and VolparaDensity™. The TOMosynthesis with digital MammographY (TOMMY) study of digital breast tomosynthesis in the Breast Screening Programme of the National Health Service (NHS) of the United Kingdom (UK) included 6020 breast screening assessment cases (of whom 1158 had breast cancer) and 1040 screened women with a family history of breast cancer (of whom two had breast cancer). We assessed the association of each measure with breast cancer risk in these populations at enhanced risk, using logistic regression adjusted for age and total breast volume as a surrogate for body mass index (BMI). All density measures showed a positive association with presence of cancer and all declined with age. The strongest effect was seen with Volpara absolute density, with a significant 3% (95% CI 1-5%) increase in risk per 10 cm 3 of dense tissue. The effect of Volpara volumetric density on risk was stronger for large and grade 3 tumours. Automated absolute breast density is a predictor of breast cancer risk in populations at enhanced risk due to either positive mammographic findings or family history. In the screening context, density could be a trigger for more intensive imaging. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  14. Contralateral breast cancer risk

    International Nuclear Information System (INIS)

    Unnithan, Jaya; Macklis, Roger M.

    2001-01-01

    The use of breast-conserving treatment approaches for breast cancer has now become a standard option for early stage disease. Numerous randomized studies have shown medical equivalence when mastectomy is compared to lumpectomy followed by radiotherapy for the local management of this common problem. With an increased emphasis on patient involvement in the therapeutic decision making process, it is important to identify and quantify any unforeseen risks of the conservation approach. One concern that has been raised is the question of radiation- related contralateral breast cancer after breast radiotherapy. Although most studies do not show statistically significant evidence that patients treated with breast radiotherapy are at increased risk of developing contralateral breast cancer when compared to control groups treated with mastectomy alone, there are clear data showing the amount of scattered radiation absorbed by the contralateral breast during a routine course of breast radiotherapy is considerable (several Gy) and is therefore within the range where one might be concerned about radiogenic contralateral tumors. While radiation related risks of contralateral breast cancer appear to be small enough to be statistically insignificant for the majority of patients, there may exist a smaller subset which, for genetic or environmental reasons, is at special risk for scatter related second tumors. If such a group could be predicted, it would seem appropriate to offer either special counselling or special prevention procedures aimed at mitigating this second tumor risk. The use of genetic testing, detailed analysis of breast cancer family history, and the identification of patients who acquired their first breast cancer at a very early age may all be candidate screening procedures useful in identifying such at- risk groups. Since some risk mitigation strategies are convenient and easy to utilize, it makes sense to follow the classic 'ALARA' (as low as reasonably

  15. Local delivery of hormonal therapy with silastic tubing for prevention and treatment of breast cancer.

    Science.gov (United States)

    Park, Jeenah; Thomas, Scott; Zhong, Allison Y; Wolfe, Alan R; Krings, Gregor; Terranova-Barberio, Manuela; Pawlowska, Nela; Benet, Leslie Z; Munster, Pamela N

    2018-01-08

    Broad use of germline testing has identified an increasing number of women at risk for breast cancer with a need for effective chemoprevention. We report a novel method to selectively deliver various anti-estrogens at high drug levels to the breast tissue by implanting a device comprised of silastic tubing. Optimized tubing properties allow elution of otherwise poorly bioavailable anti-estrogens, such as fulvestrant, into mammary tissue in vitro and in vivo with levels sufficient to inhibit estrogen receptor activation and tumor cell proliferation. Implantable silastic tubing delivers fulvestrant selectively to mouse mammary fat tissue for one year with anti-tumor effects similar to those achieved with systemic fulvestrant exposure. Furthermore, local delivery of fulvestrant significantly decreases cell proliferation, as assessed by Ki67 expression, most effectively in tumor sections adjacent to tubing. This approach may thereby introduce a potential paradigm shift and offer a promising alternative to systemic therapy for prevention and early interception of breast cancer.

  16. The direct medical costs of breast cancer in Iran: analyzing the patient′s level data from a cancer specific hospital in Isfahan

    Directory of Open Access Journals (Sweden)

    Majid Davari

    2013-01-01

    Conclusions: The direct economic cost of breast cancer in Iran is very high; nonetheless, as the age of breast cancer in Iran is nearly 10 years lower than Western countries, the burden of the disease in Iran is expected to be significantly high. Medication therapy is the main cost component of the breast cancer.

  17. Using the Internet for information about breast cancer: a questionnaire-based study.

    Science.gov (United States)

    Littlechild, Sophie Anna; Barr, Lester

    2013-09-01

    To identify the proportion of breast cancer patients that used the Internet for breast cancer information; to classify patterns of use based on patient demographics; and to evaluate whether using the Internet for this purpose was beneficial or problematic. Also to recognize whether a specific demographic group was more likely to experience problems when using the Internet for breast cancer information. A 10-item questionnaire was given to patients who attended the breast unit at the University Hospital of South Manchester between May and June 2011 following breast cancer treatment within the last 5 years. 200 questionnaires were completed. 50.5% of patients had used the Internet for breast cancer information, with younger (pincome (pInternet for breast cancer information, particularly those from ethnic minorities. Health professionals need to include a discussion about Internet use in consultations with breast cancer patients. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  18. HER2 and β-catenin protein location: importance in the prognosis of breast cancer patients and their correlation when breast cancer cells suffer stressful situations.

    Science.gov (United States)

    Cuello-Carrión, F Darío; Shortrede, Jorge E; Alvarez-Olmedo, Daiana; Cayado-Gutiérrez, Niubys; Castro, Gisela N; Zoppino, Felipe C M; Guerrero, Martín; Martinis, Estefania; Wuilloud, Rodolfo; Gómez, Nidia N; Biaggio, Verónica; Orozco, Javier; Gago, Francisco E; Ciocca, Leonardo A; Fanelli, Mariel A; Ciocca, Daniel R

    2015-02-01

    In human breast cancer, β-catenin localization has been related with disease prognosis. Since HER2-positive patients are an important subgroup, and that in breast cancer cells a direct interaction of β-catenin/HER2 has been reported, in the present study we have explored whether β-catenin location is related with the disease survival. The study was performed in a tumor bank from patients (n = 140) that did not receive specific anti-HER2 therapy. The proteins were detected by immunohistochemistry in serial sections, 47 (33.5%) patients were HER2-positive with a long follow-up. HER2-positive patients that displayed β-catenin at the plasma membrane (completely surrounding the tumour cells) showed a significant better disease-free survival and overall survival than the patients showing the protein on other locations. Then we explored the dynamics of the co-expression of β-catenin and HER2 in human MCF-7 and SKBR3 cells exposed to different stressful situations. In untreated conditions MCF-7 and SKBR3 cells showed very different β-catenin localization. In MCF-7 cells, cadmium administration caused a striking change in β-catenin localization driving it from plasma membrane to cytoplasmic and perinuclear areas and HER2 showed a similar localization patterns. The changes induced by cadmium were compared with heat shock, H2O2 and tamoxifen treatments. In conclusion, this study shows the dynamical associations of HER2 and β-catenin and their changes in subcellular localizations driven by stressful situations. In addition, we report for the first time the correlation between plasma membrane associated β-catenin in HER2-positive breast cancer and survival outcome, and the importance of the protein localization in breast cancer samples.

  19. STAT5A-mediated NOX5-L expression promotes the proliferation and metastasis of breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Dho, So Hee [Aging Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806 (Korea, Republic of); Radioisotope Research Division, Department of Research Reactor Utilization, Korea Atomic Energy Research Institute, Daejeon 305-353 (Korea, Republic of); Kim, Ji Young; Lee, Kwang-Pyo; Kwon, Eun-Soo [Aging Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806 (Korea, Republic of); Lim, Jae Cheong [Radioisotope Research Division, Department of Research Reactor Utilization, Korea Atomic Energy Research Institute, Daejeon 305-353 (Korea, Republic of); Kim, Chang-Jin [Department of Pathology, Soonchunhyang Medical Science Research Institute, Chonan 330-090 (Korea, Republic of); Jeong, Dongjun, E-mail: juny1024@sch.ac.kr [Department of Pathology, Soonchunhyang Medical Science Research Institute, Chonan 330-090 (Korea, Republic of); Kwon, Ki-Sun, E-mail: kwonks@kribb.re.kr [Aging Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806 (Korea, Republic of); Department of Functional Genomics, Korea University of Science and Technology (UST), Daejeon 305-333 (Korea, Republic of)

    2017-02-01

    NADPH oxidase (NOX) generates reactive oxygen species (ROS) and has been suggested to mediate cell proliferation in some cancers. Here, we show that an increase in the expression of NOX5 long form (NOX5-L) is critical for tumor progression in breast tumor tissues. Immunostaining of clinical samples indicated that NOX5 was overexpressed in 41.1% of breast ductal carcinoma samples. NOX5-L depletion consistently suppressed cell proliferation, invasion, and migration in vitro. Antibody-mediated neutralization of NOX5-L attenuated tumor progression in a mouse xenograft model. Promoter analysis revealed that NOX5-L expression is regulated by STAT5A in breast cancer cells. Based on our novel findings, we suggest that inhibition of NOX5-L may be a promising therapeutic strategy that exerts anti-cancer effects via the modulation of ROS-mediated cell signaling. - Highlights: • The ROS-generating protein, NOX5-L, determines cellular proliferation and metastasis in subset of breast tumor. • Tumor growth was attenuated by the treatment of anti-NOX5-L antibody in a xenograft model. • NOX5-L expression is transcriptionally regulated by STAT5A in breast cancer cells.

  20. Radiologic aspects of breast cancers detected through a breast cancer screening program

    International Nuclear Information System (INIS)

    Azavedo, E.; Svane, G.

    1991-01-01

    Early detection in breast cancer and reduced mortality in women with this disease is today attributed to widespread use of mammography. High-quality performance is essential in all steps of breast cancer screening programs in order to avoid unnecessary anxiety and surgery in the women concerned. This report presents radiologic aspects of screening cancers. A total of 8370 asymptomatic women aged 50-69 years were screened with 2-view mammography, of which only 70 (0.84 percent) were selected for surgery after a thorough work-up. Cancers were verified histologically in 61 women and 9 showed non-malignant histology, giving a cancer detection rate of 7.3 cancers per thousand screened asymptomatic women. The benign/malignant ratio in the operated cases is thus approximately 1:7. The cancers detected showed all existing types of mammographic features where 77 percent (47 cases) showed rather typical findings, such as spiculated densities both with and without microcalcifications. The results indicate that surgery can be minimized without impairing the breast cancer detection rate. Radiologists in screening programs should be aware that a large proportion of non-palpable breast cancers present in rather unconventional forms. This point is important in order to maintain a high cancer detection rate and thereby justify the widespread use of mammography as a screening tool for breast cancer in asymptomatic women. (author). 20 refs.; 1 tab