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Sample records for aggressive breast cancers

  1. Breast Cancers Between Mammograms Have Aggressive Features

    Cancer.gov

    Breast cancers that are discovered in the period between regular screening mammograms—known as interval cancers—are more likely to have features associated with aggressive behavior and a poor prognosis than cancers found via screening mammograms.

  2. Low spinophilin expression enhances aggressive biological behavior of breast cancer

    PubMed Central

    Ress, Anna Lena; Aigelsreiter, Ariane; Schauer, Silvia; Wagner, Karin; Langsenlehner, Tanja; Resel, Margit; Gerger, Armin; Ling, Hui; Ivan, Cristina; Calin, George Adrian; Hoefler, Gerald; Rinner, Beate; Pichler, Martin

    2015-01-01

    Spinophilin, a putative tumor suppressor gene, has been shown to be involved in the pathogenesis of certain types of cancer, but its role has never been systematically explored in breast cancer. In this study, we determined for the first time the expression pattern of spinophilin in human breast cancer molecular subtypes (n = 489) and correlated it with survival (n = 921). We stably reduced spinophilin expression in breast cancer cells and measured effects on cellular growth, apoptosis, anchorage-independent growth, migration, invasion and self-renewal capacity in vitro and metastases formation in vivo. Microarray profiling was used to determine the most abundantly expressed genes in spinophilin-silenced breast cancer cells. Spinophilin expression was significantly lower in basal-like breast cancer (p<0.001) and an independent poor prognostic factor in breast cancer patients (hazard ratio = 1.93, 95% confidence interval: 1.24-3.03; p = 0.004) A reduction of spinophilin levels increased cellular growth in breast cancer cells (p<0.05), without influencing activation of apoptosis. Anchorage-independent growth, migration and self-renewal capacity in vitro and metastatic potential in vivo were also significantly increased in spinophilin-silenced cells (p<0.05). Finally, we identified several differentially expressed genes in spinophilin-silenced cells. According to our data, low levels of spinophilin are associated with aggressive behavior of breast cancer. PMID:25857299

  3. Tryptophan content for monitoring breast cancer cell aggressiveness by native fluorescence spectroscopy

    NASA Astrophysics Data System (ADS)

    Zhang, Lin; Pu, Yang; Xue, Jianpeng; Pratavieira, Sebastião.; Xu, Baogang; Achilefu, Samuel; Alfano, R. R.

    2014-03-01

    This study shows tryptophan as the key native marker in cells to determine the level of aggressive cancer in breast cell lines using native fluorescence spectroscopy. An algorithm based on the ratio of tryptophan fluorescence intensity at 340 nm to intensity at 460 nm is associated with aggressiveness of the cancer cells. The higher the ratio is, the more aggressive the tumor towards metastasis.

  4. Glucose promotes breast cancer aggression and reduces metformin efficacy

    PubMed Central

    Wahdan-Alaswad, Reema; Fan, Zeying; Edgerton, Susan M; Liu, Bolin; Deng, Xin-Sheng; Arnadottir, Sigrid Salling; Richer, Jennifer K; Anderson, Steven M; Thor, Ann D

    2013-01-01

    Metformin treatment has been associated with a decrease in breast cancer risk and improved survival. Metformin induces complex cellular changes, resulting in decreased tumor cell proliferation, reduction of stem cells, and apoptosis. Using a carcinogen-induced rodent model of mammary tumorigenesis, we recently demonstrated that overfeeding in obese animals is associated with a 50% increase in tumor glucose uptake, increased proliferation, and tumor cell reprogramming to an “aggressive” metabolic state. Metformin significantly inhibited these pro-tumorigenic effects. We hypothesized that a dynamic relationship exists between chronic energy excess (glucose by dose) and metformin efficacy/action. Media glucose concentrations above 5 mmol/L was associated with significant increase in breast cancer cell proliferation, clonogenicity, motility, upregulation/activation of pro-oncogenic signaling, and reduction in apoptosis. These effects were most significant in triple-negative breast cancer (TNBC) cell lines. High-glucose conditions (10 mmol/L or above) significantly abrogated the effects of metformin. Mechanisms of metformin action at normal vs. high glucose overlapped but were not identical; for example, metformin reduced IGF-1R expression in both the HER2+ SK-BR-3 and TNBC MDA-MB-468 cell lines more significantly at 5, as compared with 10 mmol/L glucose. Significant changes in gene profiles related to apoptosis, cellular processes, metabolic processes, and cell proliferation occurred with metformin treatment in cells grown at 5 mmol/L glucose, whereas under high-glucose conditions, metformin did not significantly increase apoptotic/cellular death genes. These data indicate that failure to maintain glucose homeostasis may promote a more aggressive breast cancer phenotype and alter metformin efficacy and mechanisms of action. PMID:24107633

  5. CEST-MRI detects metabolite levels altered by breast cancer cell aggressiveness and chemotherapy response.

    PubMed

    Chan, Kannie W Y; Jiang, Lu; Cheng, Menglin; Wijnen, Jannie P; Liu, Guanshu; Huang, Peng; van Zijl, Peter C M; McMahon, Michael T; Glunde, Kristine

    2016-06-01

    Chemical exchange saturation transfer (CEST) is an MRI contrast mechanism that detects the exchange of protons from distinct hydroxyl, amine, and amide groups to tissue water through the transfer of signal loss, with repeated exchange enhancing their effective signal. We applied CEST to detect systematically 15 common cellular metabolites in a panel of differentially aggressive human breast cancer cell lines. The highest CEST contrast was generated by creatine, myo-inositol, glutamate, and glycerophosphocholine, whose cellular concentrations decreased with increasing breast cancer aggressiveness. These decreased metabolite concentrations resulted in turn in a decreased CEST profile with increasing breast cancer aggressiveness in water-soluble extracts of breast cell lines. Treatment of both breast cancer cell lines with the chemotherapy drug doxorubicin resulted in increased metabolic CEST profiles, which correlated with significant increases in creatine, phosphocreatine, and glycerophosphocholine. CEST can detect breast cancer aggressiveness and response to chemotherapy in water-soluble extracts of breast cell lines. The presented results help shed light on possible contributions from CEST-active metabolites to the CEST contrast produced by breast cancers. The metabolic CEST profile may improve detection sensitivity over conventional MRS, and may have the potential to assess breast cancer aggressiveness and response to chemotherapy non-invasively using MRI if specialized metabolic CEST profile detection can be realized in vivo. Copyright © 2016 John Wiley & Sons, Ltd. PMID:27100284

  6. USP44+ Cancer Stem Cell Subclones Contribute to Breast Cancer Aggressiveness by Promoting Vasculogenic Mimicry.

    PubMed

    Liu, Tieju; Sun, Baocun; Zhao, Xiulan; Li, Yanlei; Zhao, Xueming; Liu, Ying; Yao, Zhi; Gu, Qiang; Dong, Xueyi; Shao, Bing; Lin, Xian; Liu, Fang; An, Jindan

    2015-09-01

    Vasculogenic mimicry (VM), a newly defined pattern of tumor blood supply, describes the functional plasticity of aggressive cancer cells that form vascular networks. In our previous study, breast cancer stem cells (CSC) were shown to potentially participate in VM formation. In this study, breast CSCs presented centrosome amplification (CA) phenotype and ubiquitin-specific protease 44 (USP44) upregulation. USP44 expression contributed to the establishment of bipolar spindles in breast CSCs with supernumerary centrosomes by localizing at pole-associated centrosomes. The bipolar spindle patterns of breast CSCs with CA, including planar-like and apico-basal-like, functioned differently during the VM process of CSCs. Moreover, the ability of transendothelial migration in VM-forming cells was increased. In vivo experiment results showed that CSC xenografts presented linearly patterned programmed cell necrosis, which provided a spatial foundation for VM formation as well as angiogenesis. Breast CSCs further showed increased levels of IL6 and IL8. However, USP44 silencing induced spindle multipolarity, abated VM, reduced transendothelial migration, and consequently decreased IL6 and IL8 levels in breast CSCs. Finally, USP44(+) CSC subclones (ALDH1(+)/USP44(+)/IL6(+)/IL8(+)) were identified in breast cancer specimens through consecutive sections scanning. The subclones were related not only to CA, but also to VM. Statistical analysis suggested that USP44(+) CSC subclones could be used as an independent prognostic biomarker of poor clinical outcomes in patients with breast cancer. Collectively, the identification of USP44(+) CSC subclones may contribute to the prediction of VM formation and aggressive behavior. This study provides novel insights into the therapy for advanced breast cancer. PMID:26232424

  7. APRIL promotes breast tumor growth and metastasis and is associated with aggressive basal breast cancer.

    PubMed

    García-Castro, Araceli; Zonca, Manuela; Florindo-Pinheiro, Douglas; Carvalho-Pinto, Carla E; Cordero, Alex; Gutiérrez del Fernando, Burgo; García-Grande, Aránzazu; Mañes, Santos; Hahne, Michael; González-Suárez, Eva; Planelles, Lourdes

    2015-05-01

    APRIL (a proliferation-inducing ligand) is a cytokine of the tumor necrosis factor family associated mainly with hematologic malignancies. APRIL is also overexpressed in breast carcinoma tissue lesions, although neither its role in breast tumorigenesis nor the underlying molecular mechanism is known. Here, we show that several breast cancer cell lines express APRIL and both its receptors, B cell maturation antigen (BCMA) and transmembrane activator and CAML-interactor (TACI), independently of luminal or basal tumor cell phenotype, and that the mitogen-activated protein kinases p38, ERK1/2, and JNK1/2 are activated in response to APRIL. The inflammatory stimulus poly I:C, a toll-like receptor (TLR) 3 ligand, enhanced APRIL secretion. Silencing experiments decreased cell proliferation, demonstrating that APRIL is a critical autocrine factor for breast tumor growth. Studies of 4T1 orthotopic breast tumors in APRIL transgenic mice showed that an APRIL-enriched environment increased tumor growth and promoted lung metastasis associated with enhanced tumor cell proliferation; BCMA and TACI expression suggests that both participate in these processes. We detected APRIL, BCMA and TACI in human luminal, triple-negative breast carcinomas and HER2 breast carcinomas, with increased levels in more aggressive basal tumors. APRIL was observed near Ki67(+) nuclei and was distributed heterogeneously in the cancer cells, in the leukocyte infiltrate, and in the myoepithelial layer adjacent to the tumor area; these results imply that APRIL provides proliferation signals to tumor cells through paracrine and autocrine signaling. Our study identifies participation of APRIL signaling in breast cancer promotion; we propose impairment of this pathway as a potential therapeutic strategy. PMID:25750171

  8. Chronic psychological stress and its impact on the development of aggressive breast cancer

    PubMed Central

    Cormanique, Thayse Fachin; de Almeida, Lirane Elize Defante Ferreto; Rech, Cynthia Alba; Rech, Daniel; Herrera, Ana Cristina da Silva do Amaral; Panis, Carolina

    2015-01-01

    Objective To investigate the clinicopathological findings of women diagnosed with breast cancer and study the impact of chronic psychological stress on the pathological characteristics of these tumors. Methods We investigated a cohort composed of women diagnosed with breast cancer and divided into two groups. One group was categorized as presenting with chronic psychological stress (by using the Self-Reporting Questionnaire − SRQ-20). Another group of women with breast cancer, but with no previous history of chronic psychological stress, comprised the Control Group. Clinical and pathological data were assessed. Results Women presenting with a history of chronic distress were significantly overweight when compared to the Control Group. Furthermore, it was observed that these stressed women also had a significant percentage of aggressive breast cancer subtype, the HER2 amplified tumor, which could be putatively associated with the loss of immunosurveillance. Conclusion Our findings suggested an interaction among chronic psychological stress, overweight, and the development of more aggressive breast tumors. PMID:26466057

  9. Human Breast Cancer Invasion and Aggression Correlates with ECM Stiffening and Immune Cell Infiltration

    PubMed Central

    Acerbi, I; Cassereau, L; Dean, I; Shi, Q; Au, A; Park, C; Chen, YY; Liphardt, J; Hwang, ES; Weaver, VM

    2015-01-01

    Tumors are stiff and data suggest that the extracellular matrix stiffening that correlates with experimental mammary malignancy drives tumor invasion and metastasis. Nevertheless, the relationship between tissue and extracellular matrix stiffness and human breast cancer progression and aggression remains unclear. We undertook a biophysical and biochemical assessment of stromal-epithelial interactions in noninvasive, invasive and normal adjacent human breast tissue and in breast cancers of increasingly aggressive subtype. Our analysis revealed that human breast cancer transformation is accompanied by an incremental increase in collagen deposition and a progressive linearization and thickening of interstitial collagen. The linearization of collagen was visualized as an overall increase in tissue birefringence and was most striking at the invasive front of the tumor where the stiffness of the stroma and cellular mechanosignaling were the highest. Amongst breast cancer subtypes we found that the stroma at the invasive region of the more aggressive Basal-like and Her2 tumor subtypes was the most heterogeneous and the stiffest when compared to the less aggressive Luminal A and B subtypes. Intriguingly, we quantified the greatest number of infiltrating macrophages and the highest level of TGF beta signaling within the cells at the invasive front. We also established that stroma stiffness and the level of cellular TGF beta signaling positively correlated with each other and with the number of infiltrating tumor-activated, macrophages, which was highest in the more aggressive tumor subtypes. These findings indicate that human breast cancer progression and aggression, collagen linearization and stromal stiffening are linked and implicate tissue inflammation and TGF beta. PMID:25959051

  10. Human breast cancer invasion and aggression correlates with ECM stiffening and immune cell infiltration.

    PubMed

    Acerbi, I; Cassereau, L; Dean, I; Shi, Q; Au, A; Park, C; Chen, Y Y; Liphardt, J; Hwang, E S; Weaver, V M

    2015-10-01

    Tumors are stiff and data suggest that the extracellular matrix stiffening that correlates with experimental mammary malignancy drives tumor invasion and metastasis. Nevertheless, the relationship between tissue and extracellular matrix stiffness and human breast cancer progression and aggression remains unclear. We undertook a biophysical and biochemical assessment of stromal-epithelial interactions in noninvasive, invasive and normal adjacent human breast tissue and in breast cancers of increasingly aggressive subtype. Our analysis revealed that human breast cancer transformation is accompanied by an incremental increase in collagen deposition and a progressive linearization and thickening of interstitial collagen. The linearization of collagen was visualized as an overall increase in tissue birefringence and was most striking at the invasive front of the tumor where the stiffness of the stroma and cellular mechanosignaling were the highest. Amongst breast cancer subtypes we found that the stroma at the invasive region of the more aggressive Basal-like and Her2 tumor subtypes was the most heterogeneous and the stiffest when compared to the less aggressive luminal A and B subtypes. Intriguingly, we quantified the greatest number of infiltrating macrophages and the highest level of TGF beta signaling within the cells at the invasive front. We also established that stroma stiffness and the level of cellular TGF beta signaling positively correlated with each other and with the number of infiltrating tumor-activated macrophages, which was highest in the more aggressive tumor subtypes. These findings indicate that human breast cancer progression and aggression, collagen linearization and stromal stiffening are linked and implicate tissue inflammation and TGF beta. PMID:25959051

  11. Chronic ethanol exposure enhances the aggressiveness of breast cancer: the role of p38γ.

    PubMed

    Xu, Mei; Wang, Siying; Ren, Zhenhua; Frank, Jacqueline A; Yang, Xiuwei H; Zhang, Zhuo; Ke, Zun-Ji; Shi, Xianglin; Luo, Jia

    2016-01-19

    Both epidemiological and experimental studies suggest that ethanol may enhance aggressiveness of breast cancer. We have previously demonstrated that short term exposure to ethanol (12-48 hours) increased migration/invasion in breast cancer cells overexpressing ErbB2, but not in breast cancer cells with low expression of ErbB2, such as MCF7, BT20 and T47D breast cancer cells. In this study, we showed that chronic ethanol exposure transformed breast cancer cells that were not responsive to short term ethanol treatment to a more aggressive phenotype. Chronic ethanol exposure (10 days - 2 months) at 100 (22 mM) or 200 mg/dl (44 mM) caused the scattering of MCF7, BT20 and T47D cell colonies in a 3-dimension culture system. Chronic ethanol exposure also increased colony formation in an anchorage-independent condition and stimulated cell invasion/migration. Chronic ethanol exposure increased cancer stem-like cell (CSC) population by more than 20 folds. Breast cancer cells exposed to ethanol in vitro displayed a much higher growth rate and metastasis in mice. Ethanol selectively activated p38γ MAPK and RhoC but not p38α/β in a concentration-dependent manner. SP-MCF7 cells, a derivative of MCF7 cells which compose mainly CSC expressed high levels of phosphorylated p38γ MAPK. Knocking-down p38γ MAPK blocked ethanol-induced RhoC activation, cell scattering, invasion/migration and ethanol-increased CSC population. Furthermore, knocking-down p38γ MAPK mitigated ethanol-induced tumor growth and metastasis in mice. These results suggest that chronic ethanol exposure can enhance the aggressiveness of breast cancer by activating p38γ MAPK/RhoC pathway. PMID:26655092

  12. Whole exome sequencing of rare aggressive breast cancer histologies.

    PubMed

    Dieci, Maria Vittoria; Smutná, Veronika; Scott, Véronique; Yin, Guangliang; Xu, Ran; Vielh, Philippe; Mathieu, Marie-Christine; Vicier, Cécile; Laporte, Melanie; Drusch, Francoise; Guarneri, Valentina; Conte, Pierfranco; Delaloge, Suzette; Lacroix, Ludovic; Fromigué, Olivia; André, Fabrice; Lefebvre, Celine

    2016-02-01

    Little is known about mutational landscape of rare breast cancer (BC) subtypes. The aim of the study was to apply next generation sequencing to three different subtypes of rare BCs in order to identify new genes related to cancer progression. We performed whole exome and targeted sequencing of 29 micropapillary, 23 metaplastic, and 27 pleomorphic lobular BCs. Micropapillary BCs exhibit a profile comparable to common BCs: PIK3CA, TP53, GATA3, and MAP2K4 were the most frequently mutated genes. Metaplastic BCs presented a high frequency of TP53 (78 %) and PIK3CA (48 %) mutations and were recurrently mutated on KDM6A (13 %), a gene involved in histone demethylation. Pleomorphic lobular carcinoma exhibited high mutation rate of PIK3CA (30 %), TP53 (22 %), and CDH1 (41 %) and also presented mutations in PYGM, a gene involved in glycogen metabolism, in 8 out of 27 samples (30 %). Further analyses of publicly available datasets showed that PYGM is dramatically underexpressed in common cancers as compared to normal tissues and that low expression in tumors is correlated with poor relapse-free survival. Immunohistochemical staining on formalin-fixed paraffin-embedded tissues available in our cohort of patients confirmed higher PYGM expression in normal breast tissue compared to equivalent tumoral zone. Next generation sequencing methods applied on rare cancer subtypes can serve as a useful tool in order to uncover new potential therapeutic targets. Sequencing of pleomorphic lobular carcinoma identified a high rate of alterations in PYGM. These findings emphasize the role of glycogen metabolism in cancer progression. PMID:26907767

  13. Claudin-20 promotes an aggressive phenotype in human breast cancer cells

    PubMed Central

    Martin, Tracey A; Lane, Jane; Ozupek, Hulya; Jiang, Wen G

    2013-01-01

    Claudin-20 is a member of the Claudin family of transmembrane proteins located in the tight junction (TJ) of cells of epithelial origin. Due to the increasing evidence supporting the role of TJ proteins in preventing tumor cell metastatic behavior, this study sought to evaluate the distribution of Claudin-20 in human breast cancer and the effect of Claudin-20 overexpression in human breast cancer cells. Q-PCR data from breast cancer primary tumors (n = 114) and matched background tissue (n = 30) showed that high claudin-20 expression was correlated with poor survival of patients with breast cancer (p = 0.022). Following transformation of the breast cancer cell lines MDA-MB-231 and MCF7 with a Claudin-20 expression construct functional assays were performed to ascertain changes in cell behavior. Claudin-20 transformed cells showed significantly increased invasion (p < 0.005) and were significantly less adhesive than wild type cells (p < 0.05). There was no effect on growth (either in vitro or in vivo) for either cell line. Overexpression of Claudin-20 resulted in reduced transepithelial resistance (induced by the motogen HGF at 25 ng/ml, p = 0.0007). Interestingly, this was not mirrored by paracellular permeability, as overexpression of Claudin-20 caused a decrease in permeability. The introduction of Claudin-20 into human breast cancer cells resulted in breast cancer cells with an aggressive phenotype and reduced trans-epithelial resistance. There was no corresponding decrease in paracellular permeability, indicating that this Claudin has a differential function in epithelial TJ. This provides further insight into the importance of correctly functioning TJ in preventing the progression of human breast cancer. PMID:24665404

  14. Study in mice shows that an aggressive type of breast cancer is linked to an inflammatory protein

    Cancer.gov

    Aberrant expression of an inflammatory protein, nitric oxide synthase 2 (NOS2), may enhance the progression and metastasis of an aggressive and less common form of breast cancer, known as the estrogen receptor-negative type of disease.

  15. Breast cancer cells mechanosensing in engineered matrices: Correlation with aggressive phenotype.

    PubMed

    Li, Ji; Wu, Yang; Schimmel, Nicholas; Al-Ameen, Mohammad Ali; Ghosh, Gargi

    2016-08-01

    The pathogenesis of cancer is often driven by the modulation of the tumor microenvironment. Recent reports have highlighted that the progressive stiffening of tumor matrix is crucial for malignant transformation. Though extensive work has been done analyzing the mechanotransductive signals involved in tumor progression, it is still not clear whether the stiffness induced changes in cancer cell behavior is conserved across the invasive/aggressive phenotype of cells. Here, we used synthetic hydrogel based cell culture platform to correlate the aggressive potential of the breast cancer cells to the responses to matrix stiffness. The cellular functions such as proliferation, migration, and angiogenic capability were characterized. We report that the proliferation and motility of the highly aggressive cell line MDA-MB-231 increased with increase in matrix rigidity. We also demonstrated for the first time that the change in matrix stiffness stimulated the angiogenic activity of these cells as manifested from enhanced expression of vascular endothelial growth factor (VEGF). Inhibition of actomyosin contractility attenuated proliferation of MDA-MB-231 cells on stiff matrices while promoted the growth on soft gels. In addition, the release of VEGF was reduced upon inhibition of contractility. The less and non-aggressive breast cancer cells, SKBr3 and MCF-7 respectively displayed less dependency on matrix stiffness. PMID:26874251

  16. Sortilin is associated with breast cancer aggressiveness and contributes to tumor cell adhesion and invasion

    PubMed Central

    Roselli, Séverine; Pundavela, Jay; Demont, Yohann; Faulkner, Sam; Keene, Sheridan; Attia, John; Jiang, Chen Chen; Zhang, Xu Dong; Walker, Marjorie M.; Hondermarck, Hubert

    2015-01-01

    The neuronal membrane protein sortilin has been reported in a few cancer cell lines, but its expression and impact in human tumors is unclear. In this study, sortilin was analyzed by immunohistochemistry in a series of 318 clinically annotated breast cancers and 53 normal breast tissues. Sortilin was detected in epithelial cells, with increased levels in cancers, as compared to normal tissues (p = 0.0088). It was found in 79% of invasive ductal carcinomas and 54% of invasive lobular carcinomas (p < 0.0001). There was an association between sortilin expression and lymph node involvement (p = 0.0093), suggesting a relationship with metastatic potential. In cell culture, sortilin levels were higher in cancer cell lines compared to non-tumorigenic breast epithelial cells and siRNA knockdown of sortilin inhibited cancer cell adhesion, while proliferation and apoptosis were not affected. Breast cancer cell migration and invasion were also inhibited by sortilin knockdown, with a decrease in focal adhesion kinase and SRC phosphorylation. In conclusion, sortilin participates in breast tumor aggressiveness and may constitute a new therapeutic target against tumor cell invasion. PMID:25871389

  17. Rampant centrosome amplification underlies more aggressive disease course of triple negative breast cancers

    PubMed Central

    Pannu, Vaishali; Mittal, Karuna; Cantuaria, Guilherme; Reid, Michelle D.; Li, Xiaoxian; Donthamsetty, Shashikiran; McBride, Michelle; Klimov, Sergey; Osan, Remus; Gupta, Meenakshi V.; Rida, Padmashree C.G.; Aneja, Ritu

    2015-01-01

    Centrosome amplification (CA), a cell-biological trait, characterizes pre-neoplastic and pre-invasive lesions and is associated with tumor aggressiveness. Recent studies suggest that CA leads to malignant transformation and promotes invasion in mammary epithelial cells. Triple negative breast cancer (TNBC), a histologically-aggressive subtype shows high recurrence, metastases, and mortality rates. Since TNBC and non-TNBC follow variable kinetics of metastatic progression, they constitute a novel test bed to explore if severity and nature of CA can distinguish them apart. We quantitatively assessed structural and numerical centrosomal aberrations for each patient sample in a large-cohort of grade-matched TNBC (n = 30) and non-TNBC (n = 98) cases employing multi-color confocal imaging. Our data establish differences in incidence and severity of CA between TNBC and non-TNBC cell lines and clinical specimens. We found strong correlation between CA and aggressiveness markers associated with metastasis in 20 pairs of grade-matched TNBC and non-TNBC specimens (p < 0.02). Time-lapse imaging of MDA-MB-231 cells harboring amplified centrosomes demonstrated enhanced migratory ability. Our study bridges a vital knowledge gap by pinpointing that CA underlies breast cancer aggressiveness. This previously unrecognized organellar inequality at the centrosome level may allow early-risk prediction and explain higher tumor aggressiveness and mortality rates in TNBC patients. PMID:25868856

  18. In vivo NCL targeting affects breast cancer aggressiveness through miRNA regulation

    PubMed Central

    Palmieri, Dario; De Luca, Luciana; Consiglio, Jessica; You, Jia; Rocci, Alberto; Talabere, Tiffany; Piovan, Claudia; Lagana, Alessandro; Cascione, Luciano; Guan, Jingwen; Gasparini, Pierluigi; Balatti, Veronica; Nuovo, Gerard; Coppola, Vincenzo; Hofmeister, Craig C.; Marcucci, Guido; Byrd, John C.; Volinia, Stefano; Shapiro, Charles L.; Freitas, Michael A.

    2013-01-01

    Numerous studies have described the altered expression and the causal role of microRNAs (miRNAs) in human cancer. However, to date, efforts to modulate miRNA levels for therapeutic purposes have been challenging to implement. Here we find that nucleolin (NCL), a major nucleolar protein, posttranscriptionally regulates the expression of a specific subset of miRNAs, including miR-21, miR-221, miR-222, and miR-103, that are causally involved in breast cancer initiation, progression, and drug resistance. We also show that NCL is commonly overexpressed in human breast tumors and that its expression correlates with that of NCL-dependent miRNAs. Finally, inhibition of NCL using guanosine-rich aptamers reduces the levels of NCL-dependent miRNAs and their target genes, thus reducing breast cancer cell aggressiveness both in vitro and in vivo. These findings illuminate a path to novel therapeutic approaches based on NCL-targeting aptamers for the modulation of miRNA expression in the treatment of breast cancer. PMID:23610125

  19. In vivo NCL targeting affects breast cancer aggressiveness through miRNA regulation.

    PubMed

    Pichiorri, Flavia; Palmieri, Dario; De Luca, Luciana; Consiglio, Jessica; You, Jia; Rocci, Alberto; Talabere, Tiffany; Piovan, Claudia; Lagana, Alessandro; Cascione, Luciano; Guan, Jingwen; Gasparini, Pierluigi; Balatti, Veronica; Nuovo, Gerard; Coppola, Vincenzo; Hofmeister, Craig C; Marcucci, Guido; Byrd, John C; Volinia, Stefano; Shapiro, Charles L; Freitas, Michael A; Croce, Carlo M

    2013-05-01

    Numerous studies have described the altered expression and the causal role of microRNAs (miRNAs) in human cancer. However, to date, efforts to modulate miRNA levels for therapeutic purposes have been challenging to implement. Here we find that nucleolin (NCL), a major nucleolar protein, posttranscriptionally regulates the expression of a specific subset of miRNAs, including miR-21, miR-221, miR-222, and miR-103, that are causally involved in breast cancer initiation, progression, and drug resistance. We also show that NCL is commonly overexpressed in human breast tumors and that its expression correlates with that of NCL-dependent miRNAs. Finally, inhibition of NCL using guanosine-rich aptamers reduces the levels of NCL-dependent miRNAs and their target genes, thus reducing breast cancer cell aggressiveness both in vitro and in vivo. These findings illuminate a path to novel therapeutic approaches based on NCL-targeting aptamers for the modulation of miRNA expression in the treatment of breast cancer. PMID:23610125

  20. Recurrent ESR1-CCDC170 rearrangements in an aggressive subset of estrogen-receptor positive breast cancers

    PubMed Central

    Veeraraghavan, Jamunarani; Tan, Ying; Cao, Xi-Xi; Kim, Jin-Ah; Wang, Xian; Chamness, Gary C.; Maiti, Sourindra N.; Cooper, Laurence J. N.; Edwards, Dean P.; Contreras, Alejandro; Hilsenbeck, Susan G.; Chang, Eric C.; Schiff, Rachel; Wang, Xiao-Song

    2014-01-01

    Characterizing the genetic alterations leading to the more aggressive forms of estrogen receptor positive (ER+) breast cancers are of critical significance in breast cancer management. Here we identify recurrent rearrangements between estrogen receptor gene ESR1 and its neighbor CCDC170, which are enriched in the more aggressive and endocrine-resistant luminal-B tumors, through large-scale analyses of breast cancer transcriptome and copy number alterations. Further screening of 200 ER+ breast cancers identifies eight ESR1-CCDC170 positive tumors. These fusions encode N-terminally truncated CCDC170 proteins (ΔCCDC170). When introduced into ER+ breast cancer cells, ΔCCDC170 leads to markedly increased cell motility and anchorage-independent growth, reduced endocrine sensitivity, and enhanced xenograft tumor formation. Mechanistic studies suggest that ΔCCDC170 engages Gab1 signalosome to potentiate growth factor signaling and enhance cell motility. Together, this study identifies neoplastic ESR1-CCDC170 fusions in a more aggressive subset of ER+ breast cancer, which suggests a new concept of ER pathobiology in breast cancer. PMID:25099679

  1. MUC5B Leads to Aggressive Behavior of Breast Cancer MCF7 Cells

    PubMed Central

    Valque, Hélène; Gouyer, Valérie; Gottrand, Frédéric; Desseyn, Jean-Luc

    2012-01-01

    The mucin MUC5B has a critical protective function in the normal lung, salivary glands, esophagus, and gallbladder, and has been reported to be aberrantly expressed in breast cancer, the second leading cause of cancer-related deaths among women worldwide. To understand better the implication of MUC5B in cancer pathogenesis, the luminal human breast cancer cell line MCF7 was transfected with a vector encoding a recombinant mini-mucin MUC5B and was then infected with a virus to deliver a short hairpin RNA to knock down the mini-mucin. The proliferative and invasive properties in Matrigel of MCF7 subclones and subpopulations were evaluated in vitro. A xenograft model was established by subcutaneous inoculation of MCF7 clones and subpopulations in SCID mice. Tumor growth was measured, and the tumors and metastases were assessed by histological and immunological analysis. The mini-mucin MUC5B promoted MCF7 cell proliferation and invasion in vitro. The xenograft experiments demonstrated that the mini-mucin promoted tumor growth and MCF7 cell dissemination. In conclusion, MUC5B expression is associated with aggressive behavior of MCF7 breast cancer cells. This study suggests that MUC5B may represent a good target for slowing tumor growth and metastasis. PMID:23056409

  2. DNMT3B7 Expression Promotes Tumor Progression to a More Aggressive Phenotype in Breast Cancer Cells

    PubMed Central

    Brambert, Patrick R.; Kelpsch, Daniel J.; Hameed, Rabia; Desai, Charmi V.; Calafiore, Gianfranco; Godley, Lucy A.; Raimondi, Stacey L.

    2015-01-01

    Epigenetic changes, such as DNA methylation, have been shown to promote breast cancer progression. However, the mechanism by which cancer cells acquire and maintain abnormal DNA methylation is not well understood. We have previously identified an aberrant splice form of a DNA methyltransferase, DNMT3B7, expressed in virtually all cancer cell lines but at very low levels in normal cells. Furthermore, aggressive MDA-MB-231 breast cancer cells have been shown to express increased levels of DNMT3B7 compared to poorly invasive MCF-7 cells, indicating that DNMT3B7 may have a role in promoting a more invasive phenotype. Using data gathered from The Cancer Genome Atlas, we show that DNMT3B7 expression is increased in breast cancer patient tissues compared to normal tissue. To determine the mechanism by which DNMT3B7 was functioning in breast cancer cells, two poorly invasive breast cancer cell lines, MCF-7 and T-47D, were stably transfected with a DNMT3B7 expression construct. Expression of DNMT3B7 led to hypermethylation and down-regulation of E-cadherin, altered localization of β-catenin, as well as increased adhesion turnover, cell proliferation, and anchorage-independent growth. The novel results presented in this study suggest a role for DNMT3B7 in the progression of breast cancer to a more aggressive state and the potential for future development of novel therapeutics. PMID:25607950

  3. A lectin chromatography/mass spectrometry discovery workflow identifies putative biomarkers of aggressive breast cancers

    PubMed Central

    Drake, Penelope M.; Schilling, Birgit; Niles, Richard K.; Prakobphol, Akraporn; Li, Bensheng; Jung, Kwanyoung; Cho, Wonryeon; Braten, Miles; Inerowicz, Halina D.; Williams, Katherine; Albertolle, Matthew; Held, Jason M.; Iacovides, Demetris; Sorensen, Dylan J.; Griffith, Obi L.; Johansen, Eric; Zawadzka, Anna M.; Cusack, Michael P.; Allen, Simon; Gormley, Matthew; Hall, Steven C.; Witkowska, H. Ewa; Gray, Joe W.; Regnier, Fred; Gibson, Bradford W.; Fisher, Susan J.

    2012-01-01

    We used a lectin chromatography/MS-based approach to screen conditioned medium from a panel of luminal (less aggressive) and triple negative (more aggressive) breast cancer cell lines (n = 5/subtype). The samples were fractionated using the lectins Aleuria aurantia (AAL) and Sambucus nigra agglutinin (SNA), which recognize fucose and sialic acid, respectively. The bound fractions were enzymatically N-deglycosylated and analyzed by LC-MS/MS. In total, we identified 533 glycoproteins, ~90% of which were components of the cell surface or extracellular matrix. We observed 1011 glycosites, 100 of which were solely detected in ≥3 triple negative lines. Statistical analyses suggested that a number of these glycosites were triple negative-specific and thus potential biomarkers for this tumor subtype. An analysis of RNAseq data revealed that approximately half of the mRNAs encoding the protein scaffolds that carried potential biomarker glycosites were upregulated in triple negative vs. luminal cell lines, and that a number of genes encoding fucosyl- or sialyltransferases were differentially expressed between the two subtypes, suggesting that alterations in glycosylation may also drive candidate identification. Notably, the glycoproteins from which these putative biomarker candidates were derived are involved in cancer-related processes. Thus, they may represent novel therapeutic targets for this aggressive tumor subtype. PMID:22309216

  4. Geminin Overexpression Promotes Imatinib Sensitive Breast Cancer: A Novel Treatment Approach for Aggressive Breast Cancers, Including a Subset of Triple Negative

    PubMed Central

    Blanchard, Zannel; Mullins, Nicole; Ellipeddi, Pavani; Lage, Janice M.; McKinney, Shawn; El-Etriby, Rana; Zhang, Xu; Isokpehi, Raphael; Hernandez, Brenda; ElShamy, Wael M.

    2014-01-01

    Breast cancer is the second leading cause of cancer-related deaths in women. Triple negative breast cancer (TNBC) is an aggressive subtype that affects 10–25% mostly African American women. TNBC has the poorest prognosis of all subtypes with rapid progression leading to mortality in younger patients. So far, there is no targeted treatment for TNBC. To that end, here we show that c-Abl is one of several tyrosine kinases that phosphorylate and activate geminin’s ability to promote TNBC. Analysis of >800 breast tumor samples showed that geminin is overexpressed in ∼50% of all tumors. Although c-Abl is overexpressed in ∼90% of all tumors, it is only nuclear in geminin overexpressing tumors. In geminin-negative tumors, c-Abl is only cytoplasmic. Inhibiting c-Abl expression or activity (using imatinib or nilotinib) prevented geminin Y150 phosphorylation, inactivated the protein, and most importantly converted overexpressed geminin from an oncogene to an apoptosis inducer. In pre-clinical orthotopic breast tumor models, geminin-overexpressing cells developed aneuploid and invasive tumors, which were suppressed when c-Abl expression was blocked. Moreover, established geminin overexpressing orthotopic tumors regressed when treated with imatinib or nilotinib. Our studies support imatinib/nilotonib as a novel treatment option for patients with aggressive breast cancer (including a subset of TNBCs)-overexpressing geminin and nuclear c-Abl. PMID:24789045

  5. Cytoplasmic Cyclin E and Phospho-Cyclin-Dependent Kinase 2 Are Biomarkers of Aggressive Breast Cancer.

    PubMed

    Karakas, Cansu; Biernacka, Anna; Bui, Tuyen; Sahin, Aysegul A; Yi, Min; Akli, Said; Schafer, Jolie; Alexander, Angela; Adjapong, Opoku; Hunt, Kelly K; Keyomarsi, Khandan

    2016-07-01

    Cyclin E and its co-activator, phospho-cyclin-dependent kinase 2 (p-CDK2), regulate G1 to S phase transition and their deregulation induces oncogenesis. Immunohistochemical assessments of these proteins in cancer have been reported but were based only on their nuclear expression. However, the oncogenic forms of cyclin E (low molecular weight cyclin E or LMW-E) in complex with CDK2 are preferentially mislocalized to the cytoplasm. Here, we used separate nuclear and cytoplasmic scoring systems for both cyclin E and p-CDK2 expression to demonstrate altered cellular accumulation of these proteins using immunohistochemical analysis. We examined the specificity of different cyclin E antibodies and evaluated their concordance between immunohistochemical and Western blot analyses in a panel of 14 breast cell lines. Nuclear versus cytoplasmic staining of cyclin E readily differentiated full-length from LMW-E, respectively. We also evaluated the expression of cyclin E and p-CDK2 in 1676 breast carcinoma patients by immunohistochemistry. Cytoplasmic cyclin E correlated strongly with cytoplasmic p-CDK2 (P < 0.0001), high tumor grade, negative estrogen/progesterone receptor status, and human epidermal growth factor receptor 2 positivity (all P < 0.0001). In multivariable analysis, cytoplasmic cyclin E plus phosphorylated CDK2 (as one variable) predicted breast cancer recurrence-free and overall survival. These results suggest that cytoplasmic cyclin E and p-CDK2 can be readily detected with immunohistochemistry and used as clinical biomarkers for aggressive breast cancer. PMID:27182644

  6. The role and indications of aggressive locoregional therapy in metastatic inflammatory breast cancer.

    PubMed

    Yan, Yi; Tang, Lili; Tong, Wei; Zhou, Jingyu

    2016-01-01

    We seek to confirm the effect and explore the indications of aggressive locoregional management in patients with metastatic inflammatory breast cancer (IBC). Between 2003 and 2014, we reviewed the records of 156 patients with metastatic IBC from five large centers of Breast Surgery in the region of central south of China. Clinicopathologic data were collected to access overall survival (OS), prognostic factors and the indications for locoregional treatment. 75 (48%) patients underwent aggressive locoregional therapy. Patients in locoregional therapy group had a median OS of 24 months compared with 17 months of those in no locoregional therapy group. 2-year OS rate of these two groups was 52% and 32%, separately. Locoregional therapy (HR = 0.556; 95% CI 0.385-0.803; p = 0.002) was confirmed to be an independent prognostic factor, which could significantly improve OS of patients with metastatic IBC. For locoregional therapy group, statistical differences were observed in all subgroups stratified by the factors that were significant in univariate analysis except in the subgroups of stable disease, Charlson comorbidity index ≥3 and cerebral metastasis. Therefore, systemic therapy efficacy, Charlson comorbidity index and cerebral metastasis status appeared to be important indexes for choice of locoregional therapy in different individuals. PMID:27174789

  7. The role and indications of aggressive locoregional therapy in metastatic inflammatory breast cancer

    PubMed Central

    Yan, Yi; Tang, Lili; Tong, Wei; Zhou, Jingyu

    2016-01-01

    We seek to confirm the effect and explore the indications of aggressive locoregional management in patients with metastatic inflammatory breast cancer (IBC). Between 2003 and 2014, we reviewed the records of 156 patients with metastatic IBC from five large centers of Breast Surgery in the region of central south of China. Clinicopathologic data were collected to access overall survival (OS), prognostic factors and the indications for locoregional treatment. 75 (48%) patients underwent aggressive locoregional therapy. Patients in locoregional therapy group had a median OS of 24 months compared with 17 months of those in no locoregional therapy group. 2-year OS rate of these two groups was 52% and 32%, separately. Locoregional therapy (HR = 0.556; 95% CI 0.385–0.803; p = 0.002) was confirmed to be an independent prognostic factor, which could significantly improve OS of patients with metastatic IBC. For locoregional therapy group, statistical differences were observed in all subgroups stratified by the factors that were significant in univariate analysis except in the subgroups of stable disease, Charlson comorbidity index ≥3 and cerebral metastasis. Therefore, systemic therapy efficacy, Charlson comorbidity index and cerebral metastasis status appeared to be important indexes for choice of locoregional therapy in different individuals. PMID:27174789

  8. The β-catenin signaling pathway induces aggressive potential in breast cancer by up-regulating the chemokine CCL5.

    PubMed

    Yasuhara, Rika; Irié, Tarou; Suzuki, Kenya; Sawada, Terumasa; Miwa, Noriko; Sasaki, Akiko; Tsunoda, Yuko; Nakamura, Seigo; Mishima, Kenji

    2015-10-15

    β-Catenin signaling plays a pivotal role in the genesis of a variety of malignant tumors, but its role in breast cancer has not been fully elucidated. Here, we examined whether deregulation of β-catenin signaling is related to the aggressive characteristics of certain types of breast cancers. Analysis of cytokine levels in MDA-MB-231 cells overexpressing a constitutively active form of β-catenin (CAβ-catenin) revealed a higher level of CCL5 expression. Cells transfected with CAβ-catenin or stimulated with recombinant CCL5 exhibited increased cell invasion activity and spheroid formation in vitro. Furthermore, CAβ-catenin-transfected MDA-MB-231 cells formed larger tumor masses that contained more Ki-67-positive cells and infiltrating lymphocytes than did the control cells. An inhibitor of CCR5 and a pan-CXCR neutralizing antibody dramatically reduced CAβ-catenin-promoted activities. In addition to CCL5, 6-BIO, a chemical activator of β-catenin, induced cell invasion and spheroid formation in MDA-MB-231 cells. Furthermore, high levels of nuclear β-catenin accumulation were detected in breast cancer in patients with metastasis but not in those without metastasis. Nuclear β-catenin localization is related to increased CCL5 production in breast cancer. These findings suggest that β-catenin expression enhances tumor progression via chemokine production in breast cancers and that β-catenin signaling is a critical regulator of the aggressive traits of breast cancers. PMID:26363360

  9. Hematopoietic Age at Onset of Triple-Negative Breast Cancer Dictates Disease Aggressiveness and Progression.

    PubMed

    Marsh, Timothy; Wong, Irene; Sceneay, Jaclyn; Barakat, Amey; Qin, Yuanbo; Sjödin, Andreas; Alspach, Elise; Nilsson, Björn; Stewart, Sheila A; McAllister, Sandra S

    2016-05-15

    Triple-negative breast cancer (TNBC) is considered an early onset subtype of breast cancer that carries with it a poorer prognosis in young rather than older women for reasons that remain poorly understood. Hematopoiesis in the bone marrow becomes altered with age and may therefore affect the composition of tumor-infiltrating hematopoietic cells and subsequent tumor progression. In this study, we investigated how age- and tumor-dependent changes to bone marrow-derived hematopoietic cells impact TNBC progression. Using multiple mouse models of TNBC tumorigenesis and metastasis, we found that a specific population of bone marrow cells (BMC) upregulated CSF-1R and secreted the growth factor granulin to support stromal activation and robust tumor growth in young mice. However, the same cell population in old mice expressed low levels of CSF1R and granulin and failed to promote tumor outgrowth, suggesting that age influences the tumorigenic capacity of BMCs in response to tumor-associated signals. Importantly, BMCs from young mice were sufficient to activate a tumor-supportive microenvironment and induce tumor progression in old mice. These results indicate that hematopoietic age is an important determinant of TNBC aggressiveness and provide rationale for investigating age-stratified therapies designed to prevent the protumorigenic effects of activated BMCs. Cancer Res; 76(10); 2932-43. ©2016 AACR. PMID:27197230

  10. Breast Cancer

    MedlinePlus

    ... version of this page please turn Javascript on. Breast Cancer What is Breast Cancer? How Tumors Form The body is made up ... tumors form in the breast tissue. Who Gets Breast Cancer? Breast cancer is one of the most common ...

  11. Elevated HMGA2 expression is associated with cancer aggressiveness and predicts poor outcome in breast cancer.

    PubMed

    Wu, Jingjing; Zhang, Shizhen; Shan, Jinlan; Hu, Zujian; Liu, Xiyong; Chen, Lirong; Ren, Xingchang; Yao, Lifang; Sheng, Hongqiang; Li, Ling; Ann, David; Yen, Yun; Wang, Jian; Wang, Xiaochen

    2016-07-01

    High mobility group AT-hook 2 (HMGA2) is involved in a wide spectrum of biological processes and is upregulated in several tumors. Here, we collected 273 breast cancer (BC) specimens as a training set and 310 specimens as a validation set to examine the expression of HMGA2 by immunohistochemical staining. It was found that HMGA2 expression was significantly positively correlated with advanced tumor grade and poor survival. Subgroup analysis indicated that high level of HMGA2 was significantly correlated with poor prognosis, especially in the subgroups of stage II-III, low pathological grade and non-triple negative breast cancer cases. Gene set enrichment analysis (GSEA) demonstrated a significant positive correlation between HMGA2 level and the gene expression signature of metaplastic and mesenchymal phenotype. Importantly, we also observed that ectopic expression of HMGA2 promoted the migration and invasion of breast cancer cells, and protected cancer cells against genotoxic stress from agents stimulating P53 (Ser15) phosphorylation. As a conclusion, expression of HMGA2 might indicate more advanced malignancy of breast cancer. Thus we believe HMGA2 could serve as a biomarker of poor prognosis and a novel target in treating BC tumors. PMID:27063096

  12. LCN2 Promoter Methylation Status as Novel Predictive Marker for Microvessel Density and Aggressive Tumor Phenotype in Breast Cancer Patients.

    PubMed

    Meka, Phanni bhushann; Jarjapu, Sarika; Nanchari, Santhoshi Rani; Vishwakarma, Sandeep Kumar; Edathara, Prajitha Mohandas; Gorre, Manjula; Cingeetham, Anuradha; Vuree, Sugunakar; Annamaneni, Sandhya; Dunna, Nageswara Rao; Mukta, Srinivasulu; B, Triveni; Satti, Vishnupriya

    2015-01-01

    LCN2 (Lipocalin 2) is a 25 KD secreted acute phase protein, reported to be a novel regulator of angiogenesis in breast cancer. Up regulation of LCN2 had been observed in multiple cancers including breast cancer, pancreatic cancer and ovarian cancer. However, the role of LCN2 promoter methylation in the formation of microvessels is poorly understood. The aim of this study was to analyze the association of LCN 2 promoter methylation with microvessel formation and tumor cell proliferation in breast cancer patients. The LCN2 promoter methylation status was studied in 64 breast cancer tumors by methylation specific PCR (MSP). Evaluation of microvessel density (MVD) and Ki67 cell proliferation index was achieved by immunohistochemical staining using CD34 and MIB-1 antibodies, respectively. LCN2 promoter unmethylation status was observed in 43 (67.2%) of breast cancer patients whereas LCN2 methylation status was seen in 21 (32.8%). Further, LCN2 promoter unmethylation status was associated with aggressive tumor phenotype and elevated mean MVD in breast cancer patients. PMID:26163623

  13. Association of adiposity, dysmetabolisms, and inflammation with aggressive breast cancer subtypes: a cross-sectional study.

    PubMed

    Agresti, Roberto; Meneghini, Elisabetta; Baili, Paolo; Minicozzi, Pamela; Turco, Alberto; Cavallo, Ilaria; Funaro, Francesco; Amash, Hade; Berrino, Franco; Tagliabue, Elda; Sant, Milena

    2016-05-01

    Obesity and metabolic syndrome are risk and prognostic factors for breast cancer (BC) and are associated with chronic inflammation. We investigated the association between distinct BC subtypes and markers of adiposity, dysmetabolisms, and inflammation. We analyzed 1779 patients with primary invasive BC treated at a single institution, for whom anthropometric and clinical-pathological data were archived. BC subtypes were classified by immunohistochemical staining of ER, PR, HER2, and Ki67, and their relations with the study markers were assessed by multinomial logistic regression. Adjusted odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated taking luminal A as reference. All subtypes more aggressive than luminal A were significantly more frequent in younger (<45 years) than older women. Before menopause, luminal B HER2-negative tumors were positively associated with large waist (OR 2.55, 95 % CI 1.53-4.24) and insulin resistance (OR 1.90, 95 % CI 1.05-3.41); luminal B HER2-positive tumors with large waist (OR 2.11, 95 % CI 1.03-4.35) and triple-negative tumors with overweight (OR 3.04, 95 % CI 1.43-6.43) and high C-reactive protein (p trend = 0.026). In postmenopausal women aged <65, luminal B HER2-negative (OR 1.94, 95 % CI 1.16-3.24) and luminal B HER2-positive tumors (OR 2.48, 95 % CI 1.16-5.27) were positively related with metabolic syndrome. Dysmetabolisms and inflammation may be related to different BC subtypes. Before menopause, triple-negative cancers were related to obesity and chronic inflammation, and aggressive luminal subtypes to abdominal adiposity. After menopause, in women aged <65 these latter subtypes were related to metabolic syndrome. Control of adiposity and dysmetabolism can reduce the risk of aggressive BC subtypes, improving the prognosis. PMID:27117160

  14. Breast Cancer

    MedlinePlus

    Breast cancer affects one in eight women during their lives. Breast cancer kills more women in the United States ... cancer. No one knows why some women get breast cancer, but there are a number of risk ...

  15. Breast Cancer

    MedlinePlus

    ... 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 Overview Statistics Medical Illustrations Risk Factors Screening Symptoms ...

  16. What Is Breast Cancer?

    MedlinePlus

    ... Next Topic Types of breast cancers What is breast cancer? Breast cancer starts when cells in the breast ... breast cancer? ” and Non-cancerous Breast Conditions . How Breast Cancer Spreads Breast cancer can spread through the lymph ...

  17. LIMT is a novel metastasis inhibiting lncRNA suppressed by EGF and downregulated in aggressive breast cancer.

    PubMed

    Sas-Chen, Aldema; Aure, Miriam R; Leibovich, Limor; Carvalho, Silvia; Enuka, Yehoshua; Körner, Cindy; Polycarpou-Schwarz, Maria; Lavi, Sara; Nevo, Nava; Kuznetsov, Yuri; Yuan, Justin; Azuaje, Francisco; Ulitsky, Igor; Diederichs, Sven; Wiemann, Stefan; Yakhini, Zohar; Kristensen, Vessela N; Børresen-Dale, Anne-Lise; Yarden, Yosef

    2016-01-01

    Long noncoding RNAs (lncRNAs) are emerging as regulators of gene expression in pathogenesis, including cancer. Recently, lncRNAs have been implicated in progression of specific subtypes of breast cancer. One aggressive, basal-like subtype associates with increased EGFR signaling, while another, the HER2-enriched subtype, engages a kin of EGFR Based on the premise that EGFR-regulated lncRNAs might control the aggressiveness of basal-like tumors, we identified multiple EGFR-inducible lncRNAs in basal-like normal cells and overlaid them with the transcriptomes of over 3,000 breast cancer patients. This led to the identification of 11 prognostic lncRNAs. Functional analyses of this group uncovered LINC01089 (here renamed LncRNA Inhibiting Metastasis; LIMT), a highly conserved lncRNA, which is depleted in basal-like and in HER2-positive tumors, and the low expression of which predicts poor patient prognosis. Interestingly, EGF rapidly downregulates LIMT expression by enhancing histone deacetylation at the respective promoter. We also find that LIMT inhibits extracellular matrix invasion of mammary cells in vitro and tumor metastasis in vivo In conclusion, lncRNAs dynamically regulated by growth factors might act as novel drivers of cancer progression and serve as prognostic biomarkers. PMID:27485121

  18. Chromosomal changes in aggressive breast cancers with basal-like features

    PubMed Central

    Yu, Wayne; Kanaan, Yasmine; Bae, Young-Kyung; Gabrielson, Edward

    2009-01-01

    Using high-resolution oligonucleotide CGH arrays, we evaluated chromosomal copy number changes in a series of 16 breast cancers, selected on the basis of highly similar pathological and molecular features characteristic of the “basal-like” phenotype. Each of these cancers showed numerous gains and losses, reflecting multiple chromosomal rearrangements during the development of these high-grade cancers. Chromosomal losses were particularly prevalent on chromosomal arms 5q, 8p, 9q, 12q, 17p, 19p, and Xq, and gains were commonly seen on chromosomal arms 1q, 8q, and 17q. Particularly remarkable were regions of high-level amplification (> 8-fold copy number change) on 4q12, 8q23.3, 19p12, and 19q13.2. These regions included candidate oncogenes cKIT, JUND, and AKT2., and immunohistochemistry confirmed that these particular genes were highly expressed in the cancers harboring the specific amplifications. However, each of these amplifications was observed only in individual cases, and no particular chromosomal alteration appeared to generally characterize this group of cancers. Thus, genomic changes among breast cancers with basal-like features appear to be very heterogeneous. Distinct high-level amplifications may provide new targets for treating some of these cancers, but copy number changes do not reveal a distinctive genomic fingerprint for this proposed class of breast cancers. PMID:19602461

  19. Loss of WIF-1 and Wnt5a expression is related to aggressiveness of sporadic breast cancer in Tunisian patients.

    PubMed

    Trifa, Fatma; Karray-Chouayekh, Sondes; Jmal, Emna; Jmaa, Zeineb Ben; Khabir, Abdelmajid; Sellami-Boudawara, Tahia; Frikha, Mounir; Daoud, Jamel; Mokdad-Gargouri, Raja

    2013-06-01

    Activation of the Wnt/β-catenin signaling pathway is common in various human cancers. The aim of this study was to investigate the expression of 2 members of the Wnt family (WIF-1 and Wnt5a) in sporadic and hereditary breast cancer tissues. WIF-1, is a secreted antagonist that binds Wnt ligands, and therefore inhibits the canonical Wnt/β-catenin pathway. Wnt5a is one of the members of the noncanonical Wnt family that mainly acts through calcium signaling pathway. The expression of WIF-1 was analyzed by methylation-specific PCR and RT-PCR, and the level of Wnt5a ligand was quantified by RT-QPCR in breast cancer tissues. Methylation of WIF-1 was detected in 71.3 % and 81.8 % of sporadic and hereditary cases, respectively. Aberrant methylation of WIF-1 was associated with advanced TNM stage and triple negative cases in sporadic breast carcinoma (p=0.001 and p=0.037, respectively). In hereditary cases, methylation of WIF-1 correlated with age at diagnosis (p=0.027) and p53 status (p=0.035). Regarding patients' survival, WIF-1 methylated promoter conferred a reduced overall survival rate, and particularly in a group of patients with advanced TNM stage (p log rank=0.006). Furthermore, aberrant CpG methylation of the WIF-1 promoter was significantly associated with transcriptional silencing of this tumor suppressor gene in sporadic breast cancer tissues (p=0.036). On the other hand, in sporadic tumor tissues, the level of Wnt5a mRNA was significantly lower compared to normal tissues (p=0.031) and lower still in those showing more aggressive behavior, suggesting that Wnt5a, a ligand involved in the noncanonical Wnt/β-catenin pathway, could act as a tumor suppressor gene in breast cancer. PMID:23417837

  20. Breast cancer

    MedlinePlus

    ... of targeted therapy. It blocks certain hormones that fuel cancer growth. Cancer treatment can be local or ... breast cancer should not drink alcohol at all) Alternative Names Cancer - breast; Carcinoma - ductal; Carcinoma - lobular; DCIS; ...

  1. miR-134 in extracellular vesicles reduces triple-negative breast cancer aggression and increases drug sensitivity.

    PubMed

    O'Brien, Keith; Lowry, Michelle C; Corcoran, Claire; Martinez, Vanesa G; Daly, Melissa; Rani, Sweta; Gallagher, William M; Radomski, Marek W; MacLeod, Roderick A F; O'Driscoll, Lorraine

    2015-10-20

    Exosomes (EVs) have relevance in cell-to-cell communication carrying pro-tumorigenic factors that participate in oncogenesis and drug resistance and are proposed to have potential as self-delivery systems. Advancing on our studies of EVs in triple-negative breast cancer, here we more comprehensively analysed isogenic cell line variants and their EV populations, tissues cell line variants and their EV populations, as well as breast tumour and normal tissues. Profiling 384 miRNAs showed EV miRNA content to be highly representative of their cells of origin. miRNAs most substantially down-regulated in aggressive cells and their EVs originated from 14q32. Analysis of miR-134, the most substantially down-regulated miRNA, supported its clinical relevance in breast tumours compared to matched normal breast tissue. Functional studies indicated that miR-134 controls STAT5B which, in turn, controls Hsp90. miR-134 delivered by direct transfection into Hs578Ts(i)8 cells (in which it was greatly down-regulated) reduced STAT5B, Hsp90, and Bcl-2 levels, reduced cellular proliferation, and enhanced cisplatin-induced apoptosis. Delivery via miR-134-enriched EVs also reduced STAT5B and Hsp90, reduced cellular migration and invasion, and enhanced sensitivity to anti-Hsp90 drugs. While the differing effects achieved by transfection or EV delivery are likely to be, at least partly, due to specific amounts of miR-134 delivered by these routes, these EV-based studies identified miRNA-134 as a potential biomarker and therapeutic for breast cancer. PMID:26416415

  2. PDIA3 and PDIA6 gene expression as an aggressiveness marker in primary ductal breast cancer.

    PubMed

    Ramos, F S; Serino, L T R; Carvalho, C M S; Lima, R S; Urban, C A; Cavalli, I J; Ribeiro, E M S F

    2015-01-01

    Changes in the expression of the protein disulfide isomerase genes PDIA3 and PDIA6 may increase endoplasmic reticulum stress, leading to cellular instability and neoplasia. We evaluated the expression of PDIA3 and PDIA6 in invasive ductal carcinomas. Using reverse transcription-quantitative polymerase chain reaction, we compared the mRNA expression level in 45 samples of invasive ductal carcinoma with that in normal breast samples. Increased expression of the PDIA3 gene in carcinomas (P = 0.0009) was observed. In addition, PDIA3 expression was increased in tumors with lymph node metastasis (P = 0.009) and with grade III (P < 0.02). The PDIA6 gene showed higher expression levels in the presence of lymph node metastasis (U = 99.00, P = 0.0476) and lower expression for negative hormone receptors status (P = 0.0351). Our results suggest that alterations in PDIA3/6 expression levels may be involved in the breast carcinogenic process and should be further investigated as a marker of aggressiveness. PMID:26125904

  3. Breast Cancer

    MedlinePlus

    ... I found something when I did my breast self-exam. What should I do now? How often should I have mammograms? I have breast cancer. What are my treatment options? How often should I do breast self-exams? I have breast cancer. Is my daughter ...

  4. Breast Cancer

    MedlinePlus

    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. ...

  5. 5′-AMP-activated Protein Kinase (AMPK) Supports the Growth of Aggressive Experimental Human Breast Cancer Tumors*

    PubMed Central

    Laderoute, Keith R.; Calaoagan, Joy M.; Chao, Wan-ru; Dinh, Dominc; Denko, Nicholas; Duellman, Sarah; Kalra, Jessica; Liu, Xiaohe; Papandreou, Ioanna; Sambucetti, Lidia; Boros, Laszlo G.

    2014-01-01

    Rapid tumor growth can establish metabolically stressed microenvironments that activate 5′-AMP-activated protein kinase (AMPK), a ubiquitous regulator of ATP homeostasis. Previously, we investigated the importance of AMPK for the growth of experimental tumors prepared from HRAS-transformed mouse embryo fibroblasts and for primary brain tumor development in a rat model of neurocarcinogenesis. Here, we used triple-negative human breast cancer cells in which AMPK activity had been knocked down to investigate the contribution of AMPK to experimental tumor growth and core glucose metabolism. We found that AMPK supports the growth of fast-growing orthotopic tumors prepared from MDA-MB-231 and DU4475 breast cancer cells but had no effect on the proliferation or survival of these cells in culture. We used in vitro and in vivo metabolic profiling with [13C]glucose tracers to investigate the contribution of AMPK to core glucose metabolism in MDA-MB-231 cells, which have a Warburg metabolic phenotype; these experiments indicated that AMPK supports tumor glucose metabolism in part through positive regulation of glycolysis and the nonoxidative pentose phosphate cycle. We also found that AMPK activity in the MDA-MB-231 tumors could systemically perturb glucose homeostasis in sensitive normal tissues (liver and pancreas). Overall, our findings suggest that the contribution of AMPK to the growth of aggressive experimental tumors has a critical microenvironmental component that involves specific regulation of core glucose metabolism. PMID:24993821

  6. High levels of class III β-tubulin expression are associated with aggressive tumor features in breast cancer

    PubMed Central

    LEBOK, PATRICK; ÖZTÜRK, MELIKE; HEILENKÖTTER, UWE; JAENICKE, FRITZ; MÜLLER, VOLKMAR; PALUCHOWSKI, PETER; GEIST, STEFAN; WILKE, CHRISTIAN; BURANDT, EICKE; LEBEAU, ANNETTE; WILCZAK, WALDEMAR; KRECH, TILL; SIMON, RONALD; SAUTER, GUIDO; QUAAS, ALEXANDER

    2016-01-01

    Overexpression of class III β-tubulin (TUBB3), a factor that confers dynamic properties to microtubules, is a candidate biomarker for resistance to microtubule-targeting chemotherapeutics in breast and other types of solid cancer. Discrepant results from previous studies, with respect to the association of TUBB3 expression levels with breast cancer phenotype and patient prognosis, prompted the present study to investigate TUBB3 expression in a large cohort of breast cancer cases, with available clinical follow-up data. A preexisting breast cancer prognosis tissue microarray, containing a single 0.6 mm tissue core from each of 2,197 individual patients with breast cancer, was analyzed for TUBB3 expression by immunohistochemistry. The results of the present study revealed that TUBB3 expression was less frequent in lobular breast cancer cases (34%), compared with that of cancer cases of alternative histologies, including breast cancer of no special type (60%; P<0.0001). High TUBB3 positivity was associated with high tumor grade (P<0.0001), negativity for estrogen (P<0.0001) and progesterone receptors (P<0.004), as well as the presence of human epidermal growth factor 2 amplification (P<0.0001) and a triple-negative phenotype (P<0.0001). TUBB3 overexpression was additionally associated with reduced patient survival if all breast cancer cases of any histology were jointly analyzed (P=0.0088); however this link was not evident in the subset of breast cancer cases of no special type, or in a multivariate analysis including the established prognostic factors of tumor stage, grade and nodal stage. In conclusion, the present study demonstrated that TUBB3 overexpression was associated with adverse features of breast cancer, and that TUBB3 may possess a distinct role in lobular breast cancer cases, compared with alternative histological subtypes. The results of the present study do not support a clinically relevant role for TUBB3 as a prognostic marker in breast cancer. PMID

  7. Prostate cancer is not breast cancer

    PubMed Central

    Venniyoor, Ajit

    2016-01-01

    Cancers of the prostate and breast are hormone dependent cancers. There is a tendency to equate them and apply same algorithms for treatment. It is pointed out that metastatic prostate cancer with bone-only disease is a potentially fatal condition with a much poorer prognosis than metastatic breast cancer and needs a more aggressive approach. PMID:27051149

  8. Breast Cancer Prevention

    MedlinePlus

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

  9. Geminin overexpression-dependent recruitment and crosstalk with mesenchymal stem cells enhance aggressiveness in triple negative breast cancers

    PubMed Central

    Ananthula, Suryatheja; Sinha, Abhilasha; Gassim, Mohamed El; Batth, Simran; Marshall, Gailen D.; Gardner, Lauren H.; Shimizu, Yoshiko; ElShamy, Wael M.

    2016-01-01

    Resident mesenchymal stem cells (MSCs) promote cancer progression. However, pathways and mechanisms involved in recruiting MSCs into breast tumors remain largely undefined. Here we show that geminin-dependent acetylation releases HMGB1 from the chromatin to the cytoplasm and extracellular space. Extracellular acetylated HMGB1 (Ac-HMGB1) promotes geminin overexpressing (GemOE) cells survival by binding to RAGE and activating NF-κB signaling. Extracellular Ac-HMGB1 also triggers expression and activation of RAGE in the non-expressing MSCs. RAGE activation induces expression of CXCR4 in MSCs and directional migration towards SDF1 (aka CXCL12)-expressing GemOE cells in vitro and in vivo. These effects augmented by the necrotic and hypoxic environment in GemOE tumors, especially within their cores. Reciprocal interactions between newly recruited MSCs and GemOE tumor cells elevate tumor-initiating (TIC), basal and epithelial-to-mesenchymal transition (EMT) traits and enhance aggressiveness in vitro and in vivo in GemOE tumor cells. Indeed, faster, larger and more aggressive tumors develop when GemOE cells are co-injected with MSCs in orthotopic breast tumor model. Concurrently, inhibiting c-Abl (and thus geminin function), RAGE or CXCR4 prevented MSCs recruitment to GemOE cells in vitro and in vivo, and decreased the TIC, basal and EMT phenotypes in these tumor cells. Accordingly, we propose that GemOE tumor cells present within tumor cores represent metastatic precursors, and suppressing the GemOE→HMGB1/RAGE→SDF1/CXCR4 signaling circuit could be a valid target for therapies to inhibit GemOE tumors and their metastases. PMID:26989079

  10. Breast Cancer Cell-Derived GM-CSF Licenses Regulatory Th2 Induction by Plasmacytoid Predendritic Cells in Aggressive Disease Subtypes.

    PubMed

    Ghirelli, Cristina; Reyal, Fabien; Jeanmougin, Marine; Zollinger, Raphaël; Sirven, Philémon; Michea, Paula; Caux, Christophe; Bendriss-Vermare, Nathalie; Donnadieu, Marie-Hélène; Caly, Martial; Fourchotte, Virginie; Vincent-Salomon, Anne; Sigal-Zafrani, Brigitte; Sastre-Garau, Xavier; Soumelis, Vassili

    2015-07-15

    Reciprocal interactions between tumor cells and their microenvironment vitally impact tumor progression. In this study, we show that GM-CSF produced by primary breast tumor cells induced the activation of plasmacytoid predendritic cells (pDC), a cell type critical to anti-viral immunity. pDC that expressed the GM-CSF receptor were increased in breast tumors compared with noninvolved adjacent breast tissue. Tumor-activated pDC acquired naïve CD4(+) T-cell stimulatory capacity and promoted a regulatory Th2 response. Finally, the concomitant increase of GM-CSF and pDC was significantly associated with relatively more aggressive breast cancer subtypes. Our results characterize the first tumor-derived factor that can activate pDC to promote a regulatory Th2 response, with implications for therapeutic targeting of a tumor-immune axis of growing recognition in its significance to cancer. PMID:25977333

  11. Types of Breast Cancers

    MedlinePlus

    ... the key statistics about breast cancer? Types of breast cancers Breast cancer can be separated into different types ... than invasive ductal carcinoma. Less common types of breast cancer Inflammatory breast cancer This uncommon type of invasive ...

  12. Breast cancer.

    PubMed

    Pearce, Lynne

    2016-08-17

    Essential facts Breast cancer is the most common cancer in the UK, with around 60,000 new cases diagnosed each year, according to the charity Breast Cancer Care. Over a lifetime, women have a one in eight risk of developing it. PMID:27533387

  13. Capsaicin-induced inactivation of sensory neurons promotes a more aggressive gene expression phenotype in breast cancer cells.

    PubMed

    Erin, Nuray; Zhao, Wei; Bylander, John; Chase, Gary; Clawson, Gary

    2006-10-01

    might also be be linked to tumorigenesis via loss of its putative anti-inflammatory activities. There is anecdotal evidence in the literature to indicate that the rest of the down-regulated genes may also contribute to development of a more aggressive phenotype in this breast cancer model. PMID:16583263

  14. MYC and Breast Cancer

    PubMed Central

    Xu, Jinhua; Chen, Yinghua; Olopade, Olufunmilayo I.

    2010-01-01

    MYC is a key regulator of cell growth, proliferation, metabolism, differentiation, and apoptosis. MYC deregulation contributes to breast cancer development and progression and is associated with poor outcomes. Multiple mechanisms are involved in MYC deregulation in breast cancer, including gene amplification, transcriptional regulation, and mRNA and protein stabilization, which correlate with loss of tumor suppressors and activation of oncogenic pathways. The heterogeneity in breast cancer is increasingly recognized. Breast cancer has been classified into 5 or more subtypes based on gene expression profiles, and each subtype has distinct biological features and clinical outcomes. Among these subtypes, basal-like tumor is associated with a poor prognosis and has a lack of therapeutic targets. MYC is overexpressed in the basal-like subtype and may serve as a target for this aggressive subtype of breast cancer. Tumor suppressor BRCA1 inhibits MYC’s transcriptional and transforming activity. Loss of BRCA1 with MYC overexpression leads to the development of breast cancer—especially, basal-like breast cancer. As a downstream effector of estrogen receptor and epidermal growth factor receptor family pathways, MYC may contribute to resistance to adjuvant therapy. Targeting MYC-regulated pathways in combination with inhibitors of other oncogenic pathways may provide a promising therapeutic strategy for breast cancer, the basal-like subtype in particular. PMID:21779462

  15. Breast Cancer Overview

    MedlinePlus

    ... Breast Cancer - Overview Request Permissions Print to PDF Breast Cancer - Overview Approved by the Cancer.Net Editorial Board , ... bean-shaped organs that help fight infection. About breast cancer Cancer begins when healthy cells in the breast ...

  16. Abundant NDRG2 Expression Is Associated with Aggressiveness and Unfavorable Patients’ Outcome in Basal-Like Breast Cancer

    PubMed Central

    Gasthaus, Janina; Tiedemann, Janina; Mijnes, Jolein; Heide, Timon; Braunschweig, Till; Knüchel, Ruth; Dahl, Edgar

    2016-01-01

    NDRG2, a member of the N-myc downstream-regulated gene family, is thought to be a putative tumor suppressor gene with promising clinical impact in breast cancer. Since breast cancer comprises heterogeneous intrinsic subtypes with distinct clinical outcomes we investigated the pivotal role of NDRG2 in basal-type breast cancers. Based on subtype classified tumor (n = 45) and adjacent normal tissues (n = 17) we examined NDRG2 mRNA expression and CpG-hypermethylation, whose significance was further validated by independent data sets from The Cancer Genome Atlas (TCGA). In addition, NDRG2 protein expression was evaluated immunohistochemically using a tissue micro array (TMA, n = 211). In vitro, we investigated phenotypic effects caused by NDRG2 silencing in the basal A-like HCC1806 as well as NDRG2 over-expression in basal A-like BT20 compared to luminal-type MCF7 breast cancer cells. Our tissue collections demonstrated an overall low NDRG2 mRNA expression in breast cancer subtypes compared to normal breast tissue in line with an increased CpG-hypermethylation in breast cancer tissue. Independent TCGA data sets verified a significant (P<0.001) expression loss of NDRG2 in breast tumors. Of interest, basal-like tumors more frequently retained abundant NDRG2 expression concordant with a lower CpG-hypermethylation. Unexpectedly, basal-like breast cancer revealed an association of NDRG2 expression with unfavorable patients’ outcome. In line with this observation, in vitro experiments demonstrated reduced proliferation and migration rates (~20%) in HCC1806 cells following NDRG2 silencing. In contrast, NDRG2 over-expressing luminal-type MCF7 cells demonstrated a 26% decreased proliferation rate. Until now, this is the first study investigating the putative role of NDRG2 in depth in basal-type breast cancer. Our data indicate that the described putative tumor suppressive function of NDRG2 may be confined to luminal- and basal B-type breast cancers. PMID:27400234

  17. Breast cancer

    MedlinePlus

    ... chance that you could develop breast cancer: Some risk factors you can control, such as drinking alcohol. Others, such as family history, you cannot control. The more risk factors you have, the more your risk increases. ...

  18. Surgery for Breast Cancer

    MedlinePlus

    ... Next Topic Breast-conserving surgery (lumpectomy) Surgery for breast cancer Most women with breast cancer have some type ... Relieve symptoms of advanced cancer Surgery to remove breast cancer There are two main types of surgery to ...

  19. Learning about Breast Cancer

    MedlinePlus

    ... genetic terms used on this page Learning About Breast Cancer What do we know about heredity and breast ... Cancer What do we know about heredity and breast cancer? Breast cancer is a common disease. Each year, ...

  20. 6 Common Cancers - Breast Cancer

    MedlinePlus

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

  1. 6 Common Cancers - Breast Cancer

    MedlinePlus

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

  2. Deferoxamine-induced increase in the intracellular iron levels in highly aggressive breast cancer cells leads to increased cell migration by enhancing TNF-α-dependent NF-κB signaling and TGF-β signaling.

    PubMed

    Liu, Ping; He, Kun; Song, Hongjiao; Ma, Zhufeng; Yin, Weihai; Xu, Lisa X

    2016-07-01

    Recent studies have suggested that excess iron accumulation may be a risk factor for breast cancer. However the role of iron in breast cancer metastasis has remained unclear. The major goal of our study is to investigate the roles of iron in breast cancer metastasis. We modulated the intracellular iron levels of human breast cancer cells, including the aggressive MDA-MB-231 cells and non-aggressive MCF-7 cells, by using Deferoxamine (DFO) - a most widely used iron chelator. We found that DFO treatment could deplete intracellular iron in MCF-7 cells. In contrast, DFO treatment led to a significant increase in the intracellular iron level in MDA-MB-231 cells. The MDA-MB-231 cells with the increased intracellular iron level exhibited increases in both mesenchymal markers and cell migration. Furthermore, the DFO-treated MDA-MB-231 cells showed increases in both tumor necrosis factor α (TNF-α)-induced nuclear factor kappa B (NF-κB) signaling and transforming growth factor-β (TGF-β) signaling, which could contribute to the enhanced cell migration. Collectively, our study has provided the first evidence suggesting that increased intracellular iron levels could lead to enhanced migration of aggressive breast cancer cells by increasing TNF-α-dependent NF-κB signaling and TGF-β signaling. Our study has also suggested that caution should be taken when DFO is applied for treating breast cancer cells, since DFO could produce differential effects on the intracellular iron levels for aggressive breast cancer cells and non-aggressive breast cancer cells. PMID:27138103

  3. Preclinical Development of Novel Rac1-GEF Signaling Inhibitors using a Rational Design Approach in Highly Aggressive Breast Cancer Cell Lines

    PubMed Central

    Cardama, Georgina A; Comin, Maria J; Hornos, Leandro; Gonzalez, Nazareno; Defelipe, Lucas; Turjanski, Adrian G; Alonso, Daniel F; Gomez, Daniel E; Menna, Pablo Lorenzano

    2014-01-01

    Rho GTPases play a key role in the regulation of multiple essential cellular processes, including actin dynamics, gene transcription and cell cycle progression. Aberrant activation of Rac1, a member of Rho family of small GTPases, is associated with tumorigenesis, cancer progression, invasion and metastasis. Particularly, Rac1 is overexpressed and hyperactivated in highly aggressive breast cancer. Thus, Rac1 appears to be a promising and relevant target for the development of novel anticancer drugs. We identified the novel Rac1 inhibitor ZINC69391 through a docking-based virtual library screening targeting Rac1 activation by GEFs. This compound was able to block Rac1 interaction with its GEF Tiam1, prevented EGF-induced Rac1 activation and inhibited cell proliferation, cell migration and cell cycle progression in highly aggressive breast cancer cell lines. Moreover, ZINC69391 showed an in vivo antimetastatic effect in a syngeneic animal model. We further developed the novel analog 1A-116 by rational design and showed to be specific and more potent than the parental compound in vitro and interfered Rac1-P-Rex1 interaction. We also showed an enhanced in vivo potency of 1A-116 analog. These results show that we have developed novel Rac1 inhibitors that may be used as a novel anticancer therapy. PMID:24066799

  4. IL-1β produced by aggressive breast cancer cells is one of the factors that dictate their interactions with mesenchymal stem cells through chemokine production

    PubMed Central

    Serret, Julien; Bièche, Ivan; Brigitte, Madly; Caicedo, Andres; Sanchez, Elodie; Vacher, Sophie; Vignais, Marie-Luce; Bourin, Philippe; Geneviève, David; Molina, Franck; Jorgensen, Christian; Lazennec, Gwendal

    2015-01-01

    The aim of this work was to understand whether the nature of breast cancer cells could modify the nature of the dialog of mesenchymal stem cells (MSCs) with cancer cells. By treating MSCs with the conditioned medium of metastatic Estrogen-receptor (ER)-negative MDA-MB-231, or non-metastatic ER-positive MCF-7 breast cancer cells, we observed that a number of chemokines were produced at higher levels by MSCs treated with MDA-MB-231 conditioned medium (CM). MDA-MB-231 cells were able to induce NF-κB signaling in MSC cells. This was shown by the use of a NF-kB chemical inhibitor or an IκB dominant negative mutant, nuclear translocation of p65 and induction of NF-κB signature. Our results suggest that MDA-MB-231 cells exert their effects on MSCs through the secretion of IL-1β, that activates MSCs and induces the same chemokines as the MDA-MB-231CM. In addition, inhibition of IL-1β secretion in the MDA-MB-231 cells reduces the induced production of a panel of chemokines by MSCs, as well the motility of MDA-MB-231 cells. Our data suggest that aggressive breast cancer cells secrete IL-1β, which increases the production of chemokines by MSCs. PMID:26362269

  5. Risks of Breast Cancer Screening

    MedlinePlus

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

  6. Distinct Splice Variants and Pathway Enrichment in the Cell Line Models of Aggressive Human Breast Cancer Subtypes

    PubMed Central

    Menon, Rajasree; Im, Hogune; Zhang, Emma (Yue); Wu, Shiaw-Lin; Chen, Rui; Snyder, Michael; Hancock, William S.; Omenn, Gilbert S.

    2013-01-01

    This study was conducted as a part of the Chromosome-Centric Human Proteome Project (C-HPP) of the Human Proteome Organization. The United States team of C-HPP is focused on characterizing the protein-coding genes in chromosome 17. Despite its small size, chromosome 17 is rich in protein-coding genes, it contains many cancer-associated genes, including BRCA1, ERBB2 (Her2/neu), and TP53. The goal of this study was to examine the splice variants expressed in three ERBB2 expressed breast cancer cell line models of hormone receptor negative breast cancers by integrating RNA-Seq and proteomic mass spectrometry data. The cell-lines represent distinct phenotypic variations subtype: SKBR3 (ERBB2+ (over-expression)/ ER−/PR−; adenocarcinoma), SUM190 (ERBB2+ (over-expression)/ER−/PR−; inflammatory breast cancer) and SUM149 (ERBB2 (low expression) ER−/PR −; inflammatory breast cancer). We identified more than one splice variant for 1167 genes expressed in at least one of the three cancer cell lines. We found multiple variants of genes that are in the signaling pathways downstream of ERBB2 along with variants specific to one cancer cell line compared to the other two cancer cell lines and to normal mammary cells. The overall transcript profiles based on read counts indicated more similarities between SKBR3 and SUM190. The top-ranking Gene Ontology and BioCarta pathways for the cell-line specific variants pointed to distinct key mechanisms including: amino sugar metabolism, caspase activity, and endocytosis in SKBR3; different aspects of metabolism, especially of lipids in SUM190; cell- to-cell adhesion, integrin and ERK1/ERK2 signaling, and translational control in SUM149. The analyses indicated an enrichment in the electron transport chain processes in the ERBB2 over-expressed cell line models; and an association of nucleotide binding, RNA splicing and translation processes with the IBC models, SUM190 and SUM149. Detailed experimental studies on the distinct

  7. Bidirectional effect of CD200 on breast cancer development and metastasis, with ultimate outcome determined by tumor aggressiveness and a cancer-induced inflammatory response.

    PubMed

    Erin, N; Podnos, A; Tanriover, G; Duymuş, Ö; Cote, E; Khatri, I; Gorczynski, R M

    2015-07-01

    CD200 acts through its receptor (CD200R) to inhibit excessive inflammation. The role of CD200-CD200R1 interaction in tumor immunity is poorly understood. In this study, we examined the role of CD200-CD200R1 interaction in the progression and metastasis of highly aggressive 4THM murine-breast carcinoma using CD200 transgenic (CD200(tg)) and CD200R1 knock-out (CD200R1(-)(/-)) BALB/c mice. 4THM cells induce extensive visceral metastasis and neutrophil infiltration in affected tissues. CD200 overexpression in the host was associated with decreased primary tumor growth and metastasis, whereas lack of CD200R1 expression by host cells was associated with enhanced visceral metastasis. Absence of CD200R1 expression led to decreased tumor-infiltrating-cytotoxic T cells and increased the release of inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and interleukin (IL)-6. In contrast, CD200 overexpression led to increased tumor-induced interferon-γ and IL-10 response and decreased TNF-α and IL-6 release. Neutrophil infiltration of tissues was markedly decreased in CD200(tg) animals and increased in CD200R1(-/-) mice. These findings are contradictory to what has been reported in the EMT6 mouse breast-cancer model. Other distinguishing features of tumor elicited by EMT6 and 4THM cell injections were also examined. Visceral tissues from mice bearing EMT6 tumors showed a lack of neutrophil infiltration and decreased IL-6 release in CD200R1(-/-) mice. EMT6 and 4THM cells also differed in vimentin expression and in vitro migration rate, which was markedly lower in EMT6 tumors. These results support the hypothesis that CD200 expression can alter immune responses, and can inhibit metastatic growth of tumor cells that induce systemic and local inflammatory response. Increasing CD200 activity/signaling might be an important therapeutic strategy for treatment of aggressive breast carcinomas. PMID:25263452

  8. Breast Cancer -- Male

    MedlinePlus

    ... 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 Overview Statistics Risk Factors and Prevention ...

  9. Immunotherapy in Breast Cancer.

    PubMed

    Marmé, Frederik

    2016-01-01

    The importance of the tumor microenvironment including immune cell infiltrates in breast cancer has long been recognized. Tumor-infiltrating lymphocytes are prognostic and predictive; however, their prevalence as well as their prognostic and predictive power are subtype-dependent and appear most prominent in aggressive subtypes like triple-negative and HER2-positive disease. The immune responses observed in many cancers are attracted by tumor-associated antigens and, as suggested by recent research, by neoantigens - immunogenic antigens encoded for by non-synonymous mutations. The appealing promise of cancer vaccines has been pursued in breast cancer for over 2 decades; however, despite much effort having been put into vaccine trials, their clinical benefit, with the exception of some encouraging preliminary results, remains disappointing. The main hurdles compromising the efficacy of these vaccination strategies are the difficulties to generate broad and robust immune responses as well as to overcome immune escape mechanisms. The remarkable efficacy of immune checkpoint inhibitors in melanoma and lung cancer has set the ground for a race in the clinical development of numerous agents targeting these immune escape mechanisms in many tumor entities. Early clinical data in metastatic breast cancer suggests at least some clinical activity. This review discusses the current status and future perspectives of immunotherapy in breast cancer. PMID:27260697

  10. Mesenchyme Forkhead 1 (FOXC2) plays a key role in metastasis and is associated with aggressive basal-like breast cancers

    PubMed Central

    Mani, Sendurai A.; Yang, Jing; Brooks, Mary; Schwaninger, Gunda; Zhou, Alicia; Miura, Naoyuki; Kutok, Jeffery L.; Hartwell, Kimberly; Richardson, Andrea L.; Weinberg, Robert A.

    2007-01-01

    The metastatic spread of epithelial cancer cells from the primary tumor to distant organs mimics the cell migrations that occur during embryogenesis. Using gene expression profiling, we have found that the FOXC2 transcription factor, which is involved in specifying mesenchymal cell fate during embryogenesis, is associated with the metastatic capabilities of cancer cells. FOXC2 expression is required for the ability of murine mammary carcinoma cells to metastasize to the lung, and overexpression of FOXC2 enhances the metastatic ability of mouse mammary carcinoma cells. We show that FOXC2 expression is induced in cells undergoing epithelial-mesenchymal transitions (EMTs) triggered by a number of signals, including TGF-β1 and several EMT-inducing transcription factors, such as Snail, Twist, and Goosecoid. FOXC2 specifically promotes mesenchymal differentiation during an EMT and may serve as a key mediator to orchestrate the mesenchymal component of the EMT program. Expression of FOXC2 is significantly correlated with the highly aggressive basal-like subtype of human breast cancers. These observations indicate that FOXC2 plays a central role in promoting invasion and metastasis and that it may prove to be a highly specific molecular marker for human basal-like breast cancers. PMID:17537911

  11. Two Genes Might Help Predict Breast Cancer Survival

    MedlinePlus

    ... findings might be used to develop tests for aggressive breast cancers or to identify new targets for ... new [genetic] markers that may indicate a more aggressive type of cancer is one of the ways ...

  12. Protease Activated Receptors 1 and 2 Correlate Differently with Breast Cancer Aggressiveness Depending on Tumor ER Status

    PubMed Central

    Lidfeldt, Jon; Bendahl, Pär-Ola; Forsare, Carina; Malmström, Per; Fernö, Mårten; Belting, Mattias

    2015-01-01

    Experimental models implicate protease activated receptors (PARs) as important sensors of the proteolytic tumor microenvironment during breast cancer development. However, the role of the major PARs, PAR-1 and PAR-2, in human breast tumors remains to be elucidated. Here, we have investigated how PAR-1 and PAR-2 protein expression correlate with established clinicopathological variables and patient outcome in a well-characterized cohort of 221 breast cancer patients. Univariable and multivariable hazard ratios (HR) were estimated by the Cox proportional hazards model, distant disease-free survival (DDFS) and overall survival by the Kaplan–Meier method, and survival in different strata was determined by the log-rank test. Associations between PARs and clinicopathological variables were analyzed using Pearson’s χ2-test. We find that PAR-2 associates with DDFS (HR = 3.1, P = 0.003), whereas no such association was found with PAR-1 (HR = 1.2, P = 0.6). Interestingly, the effect of PAR-2 was confined to the ER-positive sub-group (HR = 5.5, P = 0.003 vs. HR = 1.2 in ER-negative; P = 0.045 for differential effect), and PAR-2 was an independent prognostic factor specifically in ER-positive tumors (HR = 3.9, P = 0.045). On the contrary, PAR-1 correlated with worse prognosis specifically in the ER-negative group (HR = 2.6, P = 0.069 vs. HR = 0.5, P = 0.19 in ER-positive; P = 0.026 for differential effect). This study provides novel insight into the respective roles of PAR-1 and PAR-2 in human breast cancer and suggests a hitherto unknown association between PARs and ER signaling that warrants further investigation. PMID:26244666

  13. Breast cancer screenings

    MedlinePlus

    ... this page: //medlineplus.gov/ency/patientinstructions/000837.htm Breast cancer screenings To use the sharing features on this page, please enable JavaScript. Breast cancer screenings can help find breast cancer early, before ...

  14. Breast Cancer (For Kids)

    MedlinePlus

    ... Got Homework? Here's Help White House Lunch Recipes Breast Cancer KidsHealth > For Kids > Breast Cancer Print A A ... for it when they are older. What Is Breast Cancer? The human body is made of tiny building ...

  15. Male Breast Cancer

    MedlinePlus

    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. ...

  16. Male Breast Cancer

    MedlinePlus

    Although breast cancer is much more common in women, men can get it too. It happens most often to men ... usually aren't cancer. However, most men with breast cancer have lumps. Other breast symptoms can include Dimpled ...

  17. Resistin and interleukin-6 exhibit racially-disparate expression in breast cancer patients, display molecular association and promote growth and aggressiveness of tumor cells through STAT3 activation.

    PubMed

    Deshmukh, Sachin K; Srivastava, Sanjeev K; Bhardwaj, Arun; Singh, Ajay P; Tyagi, Nikhil; Marimuthu, Saravanakumar; Dyess, Donna L; Dal Zotto, Valeria; Carter, James E; Singh, Seema

    2015-05-10

    African-American (AA) women with breast cancer (BC) are diagnosed with more aggressive disease, have higher risk of recurrence and poorer prognosis as compared to Caucasian American (CA) women. Therefore, it is imperative to define the factors associated with such disparities to reduce the unequal burden of cancer. Emerging data suggest that inherent differences exist in the tumor microenvironment of AA and CA BC patients, however, its molecular bases and functional impact have remained poorly understood. Here, we conducted cytokine profiling in serum samples from AA and CA BC patients and identified resistin and IL-6 to be the most differentially-expressed cytokines with relative greater expression in AA patients. Resistin and IL-6 exhibited positive correlation in serum levels and treatment of BC cells with resistin led to enhanced production of IL-6. Moreover, resistin also enhanced the expression and phosphorylation of STAT3, and treatment of BC cells with IL-6-neutralizing antibody prior to resistin stimulation abolished STAT3 phosphorylation. In addition, resistin promoted growth and aggressiveness of BC cells, and these effects were mediated through STAT3 activation. Together, these findings suggest a crucial role of resistin, IL-6 and STAT3 in BC racial disparity. PMID:25868978

  18. Resistin and interleukin-6 exhibit racially-disparate expression in breast cancer patients, display molecular association and promote growth and aggressiveness of tumor cells through STAT3 activation

    PubMed Central

    Bhardwaj, Arun; Singh, Ajay P.; Tyagi, Nikhil; Marimuthu, Saravanakumar; Dyess, Donna L.; Zotto, Valeria Dal; Carter, James E.; Singh, Seema

    2015-01-01

    African-American (AA) women with breast cancer (BC) are diagnosed with more aggressive disease, have higher risk of recurrence and poorer prognosis as compared to Caucasian American (CA) women. Therefore, it is imperative to define the factors associated with such disparities to reduce the unequal burden of cancer. Emerging data suggest that inherent differences exist in the tumor microenvironment of AA and CA BC patients, however, its molecular bases and functional impact have remained poorly understood. Here, we conducted cytokine profiling in serum samples from AA and CA BC patients and identified resistin and IL-6 to be the most differentially-expressed cytokines with relative greater expression in AA patients. Resistin and IL-6 exhibited positive correlation in serum levels and treatment of BC cells with resistin led to enhanced production of IL-6. Moreover, resistin also enhanced the expression and phosphorylation of STAT3, and treatment of BC cells with IL-6-neutralizing antibody prior to resistin stimulation abolished STAT3 phosphorylation. In addition, resistin promoted growth and aggressiveness of BC cells, and these effects were mediated through STAT3 activation. Together, these findings suggest a crucial role of resistin, IL-6 and STAT3 in BC racial disparity. PMID:25868978

  19. General Information about Breast Cancer

    MedlinePlus

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

  20. Breast Cancer: Treatment Options

    MedlinePlus

    ... Cancer - Treatment Options Request Permissions Print to PDF Breast Cancer - Treatment Options Approved by the Cancer.Net Editorial ... recommendations for ovarian ablation . Hormonal therapy for metastatic breast cancer Hormonal therapies are also commonly used to treat ...

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

    PubMed Central

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

    2012-01-01

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

  2. Breast Cancer Disparities

    MedlinePlus

    ... 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 ...

  3. Breast cancer in men

    MedlinePlus

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

  4. Genetic susceptibility to breast cancer.

    PubMed

    Bradbury, Angela R; Olopade, Olufunmilayo I

    2007-09-01

    Deleterious mutations in two breast and ovarian cancer susceptibility genes, BRCA1 and BRCA2 have been identified in breast and ovarian cancer families. Women with a BRCA1 or BRCA2 mutation are candidates for additional risk reduction measures such as intensive screening, prophylactic surgery or chemoprevention. Additional susceptibility genes have been identified, including PTEN, ATM, TP53, CHEK2, CASP8, PBRL and BRIP1. Yet, many women with a personal or family history suggestive of a hereditary susceptibility to breast cancer undergo genetic testing and no significant genetic alteration is found. Thus, there are other susceptibility genes that have not been identified, and it is likely that the remaining familial contribution to breast cancer will be explained by the presence of multiple low penetrance alleles that coexist to confer high penetrance risks (a polygenic model). The American Cancer Society has identified cancer prevention as a key component of cancer management and there is interest in developing individualized cancer prevention focused on identifying high risk individuals who are most likely to benefit from more aggressive risk reduction measures. Breast cancer risk assessment and genetic counseling are currently provided by genetic counselors, oncology nurse specialist, geneticists, medical and surgical oncologists, gynecologists and other health care professionals, often working within a multidisciplinary clinical setting. Current methods for risk assessment and predictive genetic testing have limitations and improvements in molecular testing and risk assessment tools is necessary to maximize individual breast cancer risk assessment and to fulfill the promise of cancer prevention. PMID:17508290

  5. Tumor apparent diffusion coefficient as an imaging biomarker to predict tumor aggressiveness in patients with estrogen-receptor-positive breast cancer.

    PubMed

    Shin, Hee Jung; Kim, So Hee; Lee, Hee Jin; Gong, Gyungyub; Baek, Seunghee; Chae, Eun Young; Choi, Woo Jung; Cha, Joo Hee; Kim, Hak Hee

    2016-08-01

    The purpose of this retrospective study was to evaluate whether tumor apparent diffusion coefficient (ADC) was correlated with pathologic biomarkers such as tumor cellularity, Ki67, tumor-infiltrating lymphocytes (TILs), and peritumoral lymphocytic infiltrate (PLI) in patients with estrogen receptor (ER)-positive breast cancer. The study was approved by the institutional review board and informed consent was waived. From July 2014 to December 2014, we reviewed 140 ER-positive tumors in 138 consecutive patients (range, 28-77 years; mean, 52 years) who underwent preoperative breast MRI and definitive surgery. All patients underwent diffusion-weighted imaging with a 3T scanner. Two radiologists drew the region of interest of the entire tumor and obtained the mean and pixel-based histogram of ADC. On pathology, two pathologists reviewed tumor cellularity, Ki67, TILs, and PLI. Multiple linear regression analysis was used to determine pathologic variables independently associated with ADC. Tumors with high tumor cellularity and high Ki67 had significantly lower ADCs than those with low tumor cellularity and low Ki67 (P < 0.05 for all). Tumors without PLI had significantly higher standard deviation than those with PLI (0.23 ± 0.08 versus 0.18 ± 0.05; P < 0.001). Median ADC was negatively correlated with tumor cellularity (r = -0.441), and Ki67 (r = -0.382). The standard deviation of ADC was also negatively correlated with the degree of PLI (r = -0.319). On multivariate linear regression analysis, tumor cellularity and Ki67 were independently associated with tumor ADC. Tumor ADC would be an MRI biomarker for the prediction of tumor aggressiveness indicators such as Ki67, tumor cellularity, and PLI in ER-positive breast cancer. Copyright © 2016 John Wiley & Sons, Ltd. PMID:27332719

  6. Hormone Therapy for Breast Cancer

    MedlinePlus

    ... Cancers Breast Cancer Screening Research Hormone Therapy for Breast Cancer On This Page What are hormones? How do ... sensitive breast cancer: Adjuvant therapy for early-stage breast cancer : Research has shown that women treated for early- ...

  7. Biomarkers to Distinguish Aggressive Cancers from Non-aggressive or Non-progressing Cancer — EDRN Public Portal

    Cancer.gov

    Distinguishing aggressive cancers from non-aggressive or non-progressing cancers is an issue of both clinical and public health importance particularly for those cancers with an available screening test. With respect to breast cancer, mammographic screening has been shown in randomized trials to reduce breast cancer mortality, but given the limitations of its sensitivity and specificity some breast cancers are missed by screening. These so called interval detected breast cancers diagnosed between regular screenings are known to have a more aggressive clinical profile. In addition, of those cancers detected by mammography some are indolent while others are more likely to recur despite treatment. The pilot study proposed herein is highly responsive to the EDRN supplement titled “Biomarkers to Distinguish Aggressive Cancers from Nonaggressive or Non-progressing Cancers” in that it addresses both of the research objectives related to these issues outlined in the notice for this supplement: Aim 1: To identify biomarkers in tumor tissue related to risk of interval detected vs. mammography screen detected breast cancer focusing on early stage invasive disease. We will compare gene expression profiles using the whole genome-cDNA-mediated Annealing, Selection, extension and Ligation (DASL) assay of 50 screen detected cancers to those of 50 interval detected cancers. Through this approach we will advance our understanding of the molecular characteristics of interval vs. screen detected breast cancers and discover novel biomarkers that distinguish between them. Aim 2: To identify biomarkers in tumor tissue related to risk of cancer recurrence among patients with screen detected early stage invasive breast cancer. Using the DASL assay we will compare gene expression profiles from screen detected early stage breast cancer that either recurred within five years or never recurred within five years. These two groups of patients will be matched on multiple factors including

  8. Epithelial-Mesenchymal Transition Phenotype Is Associated with Clinicopathological Factors That Indicate Aggressive Biological Behavior and Poor Clinical Outcomes in Invasive Breast Cancer

    PubMed Central

    Choi, Jung Eun; Kang, Su Hwan; Lee, Soo Jung

    2015-01-01

    Purpose Cancer tissue may display a wide spectrum of expression phenotypes of epithelial-mesenchymal transition (EMT)-related proteins. The purpose of this study was to investigate the clinical significance of EMT phenotypes in breast cancer. Methods We evaluated the expression pattern of the EMT-related proteins E-cadherin and fibronectin in samples from 1,495 patients with invasive breast carcinoma (IBC) on tissue microarrays using immunohistochemistry to investigate the clinical significance of EMT phenotypes in IBC. EMT phenotypes were divided into complete type (E-cadherin-negative/fibronectin-positive), incomplete type (hybrid type, E-cadherinpositive/fibronectin-positive; null type, E-cadherin-negative/fibronectin-negative), and wild-type (E-cadherin-positive/fibronectin-negative). We analyzed the correlation of EMT phenotype with clinicopathological factors and patient survival. Results Loss of E-cadherin was observed in 302 patients (20.2%), and fibronectin was expressed in the cancer cells of 354 patients (23.7%). In total, 64 (4.3%), 290 (19.4%), 238 (15.9%), and 903 (60.4%) samples were categorized as complete, hybrid, null, and wild-type, respectively. The complete EMT phenotype exhibited significant associations with young age (p=0.017), advanced pT (p<0.001) and pN (p<0.001) stages, higher histological grade (p<0.001), lymphovascular invasion (p<0.001), and triple negativity (p<0.001). Patients with complete and hybrid EMT phenotypes had poorer overall survival (OS) and disease-free survival (DFS) than those with the wild-type phenotype (OS, p=0.001; DFS, p<0.001). In multivariate analysis, the hybrid EMT phenotype was an independent prognostic factor for DFS in patients with IBC (p=0.032). Conclusion EMT phenotypes exhibited significant associations with clinicopathological factors indicating aggressive biologic behavior and poor outcome in patients with IBC. PMID:26472976

  9. [Male breast cancer].

    PubMed

    Mattson, Johanna; Vehmanen, Leena

    2016-01-01

    Breast cancer is rare in men. Diagnosis of the illness may be delayed due to the fact that the doctor and the patient fail to suspect it. Male breast cancer is treated mainly on the same principles as female breast cancer. A man affected with breast cancer should always be directed to genetic testing, as inherited mutations increasing the risk of developing cancer are more common than in female breast cancer. Most breast cancers in men are hormone receptor positive. Among hormone treatments, the antiestrogen tamoxifen exhibits the best efficacy both in early-state and advanced cases. PMID:27188086

  10. Stages of Male Breast Cancer

    MedlinePlus

    ... 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 ...

  11. Breast Cancer In Women Infographic

    Cancer.gov

    This infographic shows the Breast Cancer Subtypes in Women. It’s important for guiding treatment and predicting survival. Know the Science: HR = Hormone receptor. HR+ means tumor cells have receptors for the hormones estrogen or progesterone, which can promote the growth of HR+ tumors. Hormone therapies like tamoxifen can be used to treat HR+ tumors. HER2 = Human epidermal growth Factor receptor, HER2+ means tumor cells overexpress (make high levels of) a protein, called HE2/neu, which has been shown to be associated with certain aggressive types of breast cancer. Trastuzumab and some other therapies can target cells that overexpress HER2. HR+/HER2, aka “LuminalA”. 73% of all breast cancer cases: best prognosis, most common subtype for every race, age, and poverty level. HR-/HER2, aka “Triple Negative”: 13% of all breast cancer cases, Worst prognosis, Non-Hispanic blacks have the highest rate of this subtype at every age and poverty level. HR+/HER2+, aka “Luminal B”, 10% of all breast cancer cases, little geographic variation by state. HR-/HER2+, aka”HER2-enriched”, 5% of all breast cancer cases, lowest rates for all races and ethnicities. www.cancer.gov Source: Special section of the Annual Report to the Nation on the Status of Cancer, 1975-2011.

  12. Maternal Defense: Breast Feeding Increases Aggression by Reducing Stress

    PubMed Central

    Hahn-Holbrook, Jennifer; Holt-Lunstad, Julianne; Holbrook, Colin; Coyne, Sarah M.; Lawson, E. Thomas

    2012-01-01

    Mothers in numerous species exhibit heightened aggression in defense of their young. This shift typically coincides with the duration of lactation in nonhuman mammals, which suggests that human mothers may display similarly accentuated aggressiveness while breast feeding. Here we report the first behavioral evidence for heightened aggression in lactating humans. Breast-feeding mothers inflicted louder and longer punitive sound bursts on unduly aggressive confederates than did formula-feeding mothers or women who had never been pregnant. Maternal aggression in other mammals is thought to be facilitated by the buffering effect of lactation on stress responses. Consistent with the animal literature, our results showed that while lactating women were aggressing, they exhibited lower systolic blood pressure than did formula-feeding or never-pregnant women while they were aggressing. Mediation analyses indicated that reduced arousal during lactation may disinhibit female aggression. Together, our results highlight the contributions of breast feeding to both protecting infants and buffering maternal stress. PMID:21873570

  13. Breast cancer staging

    MedlinePlus

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

  14. Stages of Breast Cancer

    MedlinePlus

    ... to treat breast cancer. Internal radiation therapy with strontium-89 (a radionuclide ) is used to relieve bone pain ... breast cancer that has spread to the bones. Strontium-89 is injected into a vein and travels to ...

  15. Breast Cancer Treatment

    MedlinePlus

    ... to treat breast cancer. Internal radiation therapy with strontium-89 (a radionuclide ) is used to relieve bone pain ... breast cancer that has spread to the bones. Strontium-89 is injected into a vein and travels to ...

  16. Breast cancer in men

    MedlinePlus

    ... Johnson KC, Olsson H, Casagrande JT, et al. Anthropometric and hormonal risk factors for male breast cancer: ... D, Ferlay J, Brinton LA, Cook MB. An international comparison of male and female breast cancer incidence ...

  17. MicroRNA-378-mediated suppression of Runx1 alleviates the aggressive phenotype of triple negative MDA-MB-231 human breast cancer cells

    PubMed Central

    Browne, Gillian; Dragon, Julie A.; Hong, Deli; Messier, Terri L.; Gordon, Jonathan A. R.; Farina, Nicholas H.; Boyd, Joseph R.; VanOudenhove, Jennifer J.; Perez, Andrew W.; Zaidi, Sayyed K.; Stein, Janet L.; Stein, Gary S.; Lian, Jane B.

    2016-01-01

    The Runx1 transcription factor, known for its essential role normal hematopoiesis, was reported in limited studies to be mutated or associated with human breast tumor tissues. Runx 1 increases concomitant with disease progression in the MMTV-PyMT transgenic mouse model of breast cancer. Compelling questions relate to mechanisms that regulate Runx1 expression in breast cancer. Here, we tested the hypothesis that dysregulation of Runx1-targeting microRNAs (miRNAs) allows for pathologic increase of Runx1 during breast cancer progression. Microarray profiling of the MMTV-PyMT model revealed significant down-regulation of numerous miRNAs predicted to target Runx1. One of these, miR-378, was inversely correlated with Runx1 expression during breast cancer progression in mouse, and in human breast cancer cell lines MCF7 and triple negative MDA-MB-231 that represent early and late stage disease, respectively. MiR-378 is nearly absent in MDA-MB-231 cells. Luciferase reporter assays revealed that miR-378 binds the Runx1 3′UTR and inhibits Runx1 expression. Functionally, we demonstrated that ectopic expression of miR-378 in MDA-MB-231 cells inhibited Runx1 and suppressed migration and invasion; while inhibition of miR-378 in MCF7 cells increased Runx1 levels and cell migration. Depletion of Runx1 in late stage breast cancer cells resulted in increased expression of both the miR-378 host gene PPARGC1B and pre-miR-378, suggesting a feedback loop. Taken together, our study identifies a novel and clinically relevant mechanism for regulation of Runx1 in breast cancer that is mediated by a PPARGC1B-miR-378-Runx1 regulatory pathway. Our results highlight the translational potential of miRNA replacement therapy for inhibiting Runx1 in breast cancer. PMID:26749280

  18. Stratification and therapeutic potential of PML in metastatic breast cancer

    PubMed Central

    Martín-Martín, Natalia; Piva, Marco; Urosevic, Jelena; Aldaz, Paula; Sutherland, James D.; Fernández-Ruiz, Sonia; Arreal, Leire; Torrano, Verónica; Cortazar, Ana R.; Planet, Evarist; Guiu, Marc; Radosevic-Robin, Nina; Garcia, Stephane; Macías, Iratxe; Salvador, Fernando; Domenici, Giacomo; Rueda, Oscar M.; Zabala-Letona, Amaia; Arruabarrena-Aristorena, Amaia; Zúñiga-García, Patricia; Caro-Maldonado, Alfredo; Valcárcel-Jiménez, Lorea; Sánchez-Mosquera, Pilar; Varela-Rey, Marta; Martínez-Chantar, Maria Luz; Anguita, Juan; Ibrahim, Yasir H.; Scaltriti, Maurizio; Lawrie, Charles H.; Aransay, Ana M.; Iovanna, Juan L.; Baselga, Jose; Caldas, Carlos; Barrio, Rosa; Serra, Violeta; dM Vivanco, Maria; Matheu, Ander; Gomis, Roger R.; Carracedo, Arkaitz

    2016-01-01

    Patient stratification has been instrumental for the success of targeted therapies in breast cancer. However, the molecular basis of metastatic breast cancer and its therapeutic vulnerabilities remain poorly understood. Here we show that PML is a novel target in aggressive breast cancer. The acquisition of aggressiveness and metastatic features in breast tumours is accompanied by the elevated PML expression and enhanced sensitivity to its inhibition. Interestingly, we find that STAT3 is responsible, at least in part, for the transcriptional upregulation of PML in breast cancer. Moreover, PML targeting hampers breast cancer initiation and metastatic seeding. Mechanistically, this biological activity relies on the regulation of the stem cell gene SOX9 through interaction of PML with its promoter region. Altogether, we identify a novel pathway sustaining breast cancer aggressiveness that can be therapeutically exploited in combination with PML-based stratification. PMID:27553708

  19. Stratification and therapeutic potential of PML in metastatic breast cancer.

    PubMed

    Martín-Martín, Natalia; Piva, Marco; Urosevic, Jelena; Aldaz, Paula; Sutherland, James D; Fernández-Ruiz, Sonia; Arreal, Leire; Torrano, Verónica; Cortazar, Ana R; Planet, Evarist; Guiu, Marc; Radosevic-Robin, Nina; Garcia, Stephane; Macías, Iratxe; Salvador, Fernando; Domenici, Giacomo; Rueda, Oscar M; Zabala-Letona, Amaia; Arruabarrena-Aristorena, Amaia; Zúñiga-García, Patricia; Caro-Maldonado, Alfredo; Valcárcel-Jiménez, Lorea; Sánchez-Mosquera, Pilar; Varela-Rey, Marta; Martínez-Chantar, Maria Luz; Anguita, Juan; Ibrahim, Yasir H; Scaltriti, Maurizio; Lawrie, Charles H; Aransay, Ana M; Iovanna, Juan L; Baselga, Jose; Caldas, Carlos; Barrio, Rosa; Serra, Violeta; Vivanco, Maria dM; Matheu, Ander; Gomis, Roger R; Carracedo, Arkaitz

    2016-01-01

    Patient stratification has been instrumental for the success of targeted therapies in breast cancer. However, the molecular basis of metastatic breast cancer and its therapeutic vulnerabilities remain poorly understood. Here we show that PML is a novel target in aggressive breast cancer. The acquisition of aggressiveness and metastatic features in breast tumours is accompanied by the elevated PML expression and enhanced sensitivity to its inhibition. Interestingly, we find that STAT3 is responsible, at least in part, for the transcriptional upregulation of PML in breast cancer. Moreover, PML targeting hampers breast cancer initiation and metastatic seeding. Mechanistically, this biological activity relies on the regulation of the stem cell gene SOX9 through interaction of PML with its promoter region. Altogether, we identify a novel pathway sustaining breast cancer aggressiveness that can be therapeutically exploited in combination with PML-based stratification. PMID:27553708

  20. Breast Cancer Rates by State

    MedlinePlus

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

  1. (18)F-FDG PET/CT in the early prediction of pathological response in aggressive subtypes of breast cancer: review of the literature and recommendations for use in clinical trials.

    PubMed

    Groheux, David; Mankoff, David; Espié, Marc; Hindié, Elif

    2016-05-01

    Early assessment of response to neoadjuvant chemotherapy (NAC) might be helpful in avoiding the toxicity of ineffective chemotherapy and allowing refinement of treatment. We conducted a review of the literature regarding the applicability of (18)F-FDG PET/CT to the prediction of an early pathological response in different subgroups of breast cancer. Clinical research in this field has intensified in the last few years. Early studies by various groups have shown the potential of (18)F-FDG PET/CT in the early assessment of response to NAC. However, interim PET/CT in breast cancer has not yet gained wide acceptance compared to its use in other settings such as lymphomas. This is in part due to a lack of consensus that early evaluation of response can be used to direct change in therapy in the neoadjuvant breast cancer setting, and only limited data showing that response-adaptive therapy leads to improved outcomes. However, one major element that has hampered the use of (18)F-FDG PET/CT in directing neoadjuvant therapy is its evaluation in populations with mixed subtypes of breast cancer. However, major improvements have occurred in recent years. Pilot studies have highlighted the need for considering breast cancer subtype and the type of treatment, and have offered criteria for the use of PET/CT for the early prediction of response in specific settings. (18)F-FDG PET/CT has considerable potential for the early prediction of pathological complete response to NAC in aggressive subtypes such as triple-negative or HER2-positive breast cancers. The results of a multicentre trial that used early metabolic response on (18)F-FDG PET/CT as a means to select poor responders to adapt neoadjuvant treatment have recently been published. Other trials are ongoing or being planned. PMID:26758726

  2. Overcoming radiation resistance in inflammatory breast cancer.

    PubMed

    Woodward, Wendy A; Debeb, Bisrat G; Xu, Wei; Buchholz, Thomas A

    2010-06-01

    The clinical-pathological features of inflammatory breast cancer include enrichment of factors that have been previously associated with radioresistant disease, including negative hormone receptor status and a phenotype enriched for relatively radioresistant breast cancer stem/progenitor cells. The risks and benefits of accelerated postmastectomy radiation treatment regimens in the multimodality management of inflammatory breast cancer were reviewed at the first International Inflammatory Breast Cancer Conference at The University of Texas M. D. Anderson Cancer Center. The biological basis for radiation resistance and strategies to radiosensitize these tumors were also presented. The prevalent basal phenotype of inflammatory breast cancer makes it an ideal clinical model to examine stem cell hypotheses, which the authors believe can help guide future trials to continue making incremental progress against this aggressive disease. PMID:20503417

  3. Breast Cancer Screening

    MedlinePlus

    ... the chance of dying from breast cancer. MRI (magnetic resonance imaging) in women with a high risk of breast ... the body. This procedure is also called nuclear magnetic resonance imaging (NMRI). MRI does not use any x-rays. ...

  4. Living as a Breast Cancer Survivor

    MedlinePlus

    ... Emotional aspects of breast cancer Living as a breast cancer survivor For many women with breast cancer, treatment ... making some new choices. Follow-up care after breast cancer treatment Even after you have completed breast cancer ...

  5. Breast Cancer Risk in American Women

    MedlinePlus

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

  6. Genetics Home Reference: breast cancer

    MedlinePlus

    ... Me Understand Genetics Home Health Conditions breast cancer breast cancer Enable Javascript to view the expand/collapse boxes. Download PDF Open All Close All Description Breast cancer is a disease in which certain cells in ...

  7. Intracellular expression of inflammatory proteins S100A8 and S100A9 leads to epithelial-mesenchymal transition and attenuated aggressivity of breast cancer cells.

    PubMed

    Cormier, Kevin; Harquail, Jason; Ouellette, Rodney J; Tessier, Philippe A; Guerrette, Roxann; Robichaud, Gilles A

    2014-01-01

    S100 inflammatory proteins have been previously shown to modulate breast cancer processes. More specifically, genome-wide transcriptome studies associate S100A8 and S100A9 members to breast cancer progression and malignancy. Findings have shown that S100A8 and S100A9 can signal and regulate cancer cell behavior through both extracellular and intracellular-initiated cascades. However, functional studies exploring the effects of S100 proteins are often contradictory leaving ambiguity and a paucity of data relating to the specific function of S100A8 and S100A9 in breast cancer progression. In this study we sought to better define the functions of intracellular expressed S100A8 and S100A9 on key signaling and cellular processes driving breast cancer malignancy. We observed that extracellular treatments of the MCF7 breast cancer cell line with S100A8 and S100A9 proteins induces cell proliferation. In contrast, intracellular recombinant expression of S100A8 and S100A9 led to growth suppression. Furthermore our analysis revealed that intracellular-expressed S100A8 and S100A9 promote an epithelial-like phenotype through the induction of key markers, such as Ecadherin, integrin alpha-5 and Zona Occludens 1 (ZO-1). Concomitantly, S100A8 and S100A9 negatively regulate the activity of the promalignant Focal Adhesion Kinase-1 (FAK) signaling cascade leading to changes in cell adhesion and invasion properties. Our results uncover important differences in intracellular versus extracellular initiated S100A8 and S100A9 signaling cascades and their effects on mammary epithelial growth. Importantly, S100A8 and S100A9 appear to suppress breast cancer malignancy through an increase in mesenchymal to epithelial transitioning. Our findings shed insight into S100 protein involvement in breast cancer invasiveness and metastasis and clarify some of the controversies relating to these proteins in breast cancer processes. PMID:24041228

  8. Claudin 1 in Breast Cancer: New Insights

    PubMed Central

    Zhou, Bowen; Moodie, Amanda; Blanchard, Anne A. A.; Leygue, Etienne; Myal, Yvonne

    2015-01-01

    Claudin 1 is a small transmembrane protein responsible for maintaining the barrier function that exists between epithelial cells. A tight junction protein that regulates the paracellular transport of small ions across adjacent cells, claudin 1 maintains cellular polarity and plays a major role in cell-cell communication and epithelial cell homeostasis. Long considered to be a putative tumor suppressor in human breast cancer, new studies suggest a role much more complex. While most invasive breast cancers exhibit a down regulation or absence of claudin 1, some aggressive subtypes that exhibit high claudin 1 levels have now been described. Furthermore, a causal role for claudin 1 in breast cancer progression has recently been demonstrated in some breast cancer cell lines. In this review we highlight new insights into the role of claudin 1 in breast cancer, including its involvement in collective migration and epithelial mesenchymal transition (EMT). PMID:26633531

  9. Claudin 1 in Breast Cancer: New Insights.

    PubMed

    Zhou, Bowen; Moodie, Amanda; Blanchard, Anne A A; Leygue, Etienne; Myal, Yvonne

    2015-01-01

    Claudin 1 is a small transmembrane protein responsible for maintaining the barrier function that exists between epithelial cells. A tight junction protein that regulates the paracellular transport of small ions across adjacent cells, claudin 1 maintains cellular polarity and plays a major role in cell-cell communication and epithelial cell homeostasis. Long considered to be a putative tumor suppressor in human breast cancer, new studies suggest a role much more complex. While most invasive breast cancers exhibit a down regulation or absence of claudin 1, some aggressive subtypes that exhibit high claudin 1 levels have now been described. Furthermore, a causal role for claudin 1 in breast cancer progression has recently been demonstrated in some breast cancer cell lines. In this review we highlight new insights into the role of claudin 1 in breast cancer, including its involvement in collective migration and epithelial mesenchymal transition (EMT). PMID:26633531

  10. Chemoprevention of breast cancer.

    PubMed

    Files, Julia A; Stan, Daniela L; Allen, Summer V; Pruthi, Sandhya

    2012-11-01

    The development of pharmacologic agents for the prevention of breast cancer is a significant milestone in medical and laboratory research. Despite these advances, the endorsement of preventive options has become challenging and complex, as physicians are expected to counsel and tailor their recommendations using a personalized approach taking into account medical comorbidities, degree of risk and patient preferences. This article provides a comprehensive overview of the major breast cancer prevention trials, review of the pharmacologic options available for breast cancer prevention, and strategies for integrating chemoprevention of breast cancer in high-risk women into clinical practice. PMID:23181529

  11. Carboplatin and Eribulin Mesylate in Triple Negative Breast Cancer Patients

    ClinicalTrials.gov

    2016-06-30

    Estrogen Receptor-negative Breast Cancer; HER2-negative Breast Cancer; Male Breast Cancer; Progesterone Receptor-negative Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Triple-negative Breast Cancer

  12. BREAST CANCER AND EXERCISE

    ClinicalTrials.gov

    2008-03-19

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

  13. Breast Cancer in Men

    MedlinePlus

    ... This may result in a delay in diagnosis. Survival is highest when breast cancer is found early. If you notice any of ... chest or nipple, see a doctor right away. Survival rates are similar for men and women when breast cancer is found at the same stage. A man’s ...

  14. Analysis of gene expression of secreted factors associated with breast cancer metastases in breast cancer subtypes

    PubMed Central

    Fertig, Elana J.; Lee, Esak; Pandey, Niranjan B.; Popel, Aleksander S.

    2015-01-01

    Breast cancer is a heterogeneous disease, having multiple subtypes with different malignant phenotypes. The triple-negative breast cancer, or basal breast cancer, is highly aggressive, metastatic, and difficult to treat. Previously, we identified that key molecules (IL6, CSF2, CCL5, VEGFA, and VEGFC) secreted by tumor cells and stromal cells in basal breast cancer can promote metastasis. It remains to assess whether these molecules function similarly in other subtypes of breast cancer. Here, we characterize the relative gene expression of the five secreted molecules and their associated receptors (GP130, GMRA, GMRB, CCR5, VEGFR2, NRP1, VEGFR3, NRP2) in the basal, HER2 (human epidermal growth factor receptor 2) positive, luminal A, and luminal B subtypes using high throughput data from tumor samples in The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC). IL6 and CCL5 gene expression are basal breast cancer specific, whereas high gene expression of GP130 was observed in luminal A/B. VEGFA/C and CSF2 mRNA are overexpressed in HER2 positive breast cancer, with VEGFA and CSF2 also overexpressed in basal breast cancer. Further study of the specific protein function of these factors within their associated cancer subtypes may yield personalized biomarkers and treatment modalities. PMID:26173622

  15. Analysis of gene expression of secreted factors associated with breast cancer metastases in breast cancer subtypes.

    PubMed

    Fertig, Elana J; Lee, Esak; Pandey, Niranjan B; Popel, Aleksander S

    2015-01-01

    Breast cancer is a heterogeneous disease, having multiple subtypes with different malignant phenotypes. The triple-negative breast cancer, or basal breast cancer, is highly aggressive, metastatic, and difficult to treat. Previously, we identified that key molecules (IL6, CSF2, CCL5, VEGFA, and VEGFC) secreted by tumor cells and stromal cells in basal breast cancer can promote metastasis. It remains to assess whether these molecules function similarly in other subtypes of breast cancer. Here, we characterize the relative gene expression of the five secreted molecules and their associated receptors (GP130, GMRA, GMRB, CCR5, VEGFR2, NRP1, VEGFR3, NRP2) in the basal, HER2 (human epidermal growth factor receptor 2) positive, luminal A, and luminal B subtypes using high throughput data from tumor samples in The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC). IL6 and CCL5 gene expression are basal breast cancer specific, whereas high gene expression of GP130 was observed in luminal A/B. VEGFA/C and CSF2 mRNA are overexpressed in HER2 positive breast cancer, with VEGFA and CSF2 also overexpressed in basal breast cancer. Further study of the specific protein function of these factors within their associated cancer subtypes may yield personalized biomarkers and treatment modalities. PMID:26173622

  16. CDC Vital Signs: Breast Cancer

    MedlinePlus

    ... 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 ...

  17. Breast Cancer and Bone Loss

    MedlinePlus

    ... Balance › Breast Cancer and Bone Loss Fact Sheet Breast Cancer and Bone Loss July, 2010 Download PDFs English ... JoAnn Pinkerton, MD What is the link between breast cancer and bone loss? Certain treatments for breast cancer ...

  18. Abortion, Miscarriage, and Breast Cancer Risk

    MedlinePlus

    ... Cancers Breast Cancer Screening Research Abortion, Miscarriage, and Breast Cancer Risk A woman’s hormone levels normally change throughout ... the development of breast cancer. Important Information about Breast Cancer Risk Factors At present, the factors known to ...

  19. MMP1, MMP9, and COX2 Expressions in Promonocytes Are Induced by Breast Cancer Cells and Correlate with Collagen Degradation, Transformation-Like Morphological Changes in MCF-10A Acini, and Tumor Aggressiveness

    PubMed Central

    Chimal-Ramírez, G. K.; Espinoza-Sánchez, N. A.; Utrera-Barillas, D.; Benítez-Bribiesca, L.; Velázquez, J. R.; Arriaga-Pizano, L. A.; Monroy-García, A.; Reyes-Maldonado, E.; Domínguez-López, M. L.; Piña-Sánchez, Patricia; Fuentes-Pananá, E. M.

    2013-01-01

    Tumor-associated immune cells often lack immune effector activities, and instead they present protumoral functions. To understand how tumors promote this immunological switch, invasive and noninvasive breast cancer cell (BRC) lines were cocultured with a promonocytic cell line in a Matrigel-based 3D system. We hypothesized that if communication exists between tumor and immune cells, coculturing would result in augmented expression of genes associated with tumor malignancy. Upregulation of proteases MMP1 and MMP9 and inflammatory COX2 genes was found likely in response to soluble factors. Interestingly, changes were more apparent in promonocytes and correlated with the aggressiveness of the BRC line. Increased gene expression was confirmed by collagen degradation assays and immunocytochemistry of prostaglandin 2, a product of COX2 activity. Untransformed MCF-10A cells were then used as a sensor of soluble factors with transformation-like capabilities, finding that acini formed in the presence of supernatants of the highly aggressive BRC/promonocyte cocultures often exhibited total loss of the normal architecture. These data support that tumor cells can modify immune cell gene expression and tumor aggressiveness may importantly reside in this capacity. Modeling interactions in the tumor stroma will allow the identification of genes useful as cancer prognostic markers and therapy targets. PMID:23762835

  20. Women with Disabilities and Breast Cancer Screening

    MedlinePlus

    ... and Reasonable Accommodations (RA) Women with Disabilities and Breast Cancer Screening Recommend on Facebook Tweet Share Compartir Finding Breast Cancer Early Can Save Lives Disabilities & Breast Cancer Screening ...

  1. Nodal signaling promotes a tumorigenic phenotype in human breast cancer.

    PubMed

    Kirsammer, Gina; Strizzi, Luigi; Margaryan, Naira V; Gilgur, Alina; Hyser, Matthew; Atkinson, Janis; Kirschmann, Dawn A; Seftor, Elisabeth A; Hendrix, Mary J C

    2014-12-01

    The Ras-ERK pathway is deregulated in approximately a third of human cancers, particularly those of epithelial origin. In aggressive, triple-negative, basal-like breast cancers, most tumors display increased MEK and ERK phosphorylation and exhibit a gene expression profile characteristic of Kras or EGFR mutant tumors; however, Ras family genetic mutations are uncommon in triple-negative breast cancer and EGFR mutations account for only a subset of these tumors. Therefore, the upstream events that activate MAPK signaling and promote tumor aggression in triple-negative breast cancers remain poorly defined. We have previously shown that a secreted TGF-β family signaling ligand, Nodal, is expressed in breast cancer in correlation with disease progression. Here we highlight key findings demonstrating that Nodal is required in aggressive human breast cancer cells to activate ERK signaling and downstream tumorigenic phenotypes both in vitro and in vivo. Experimental knockdown of Nodal signaling downregulates ERK activity, resulting in loss of c-myc, upregulation of p27, G1 cell cycle arrest, increased apoptosis and decreased tumorigenicity. The data suggest that ERK activation by Nodal signaling regulates c-myc and p27 proteins post-translationally and that this cascade is essential for aggressive breast tumor behavior in vivo. As the MAPK pathway is an important target for treating triple-negative breast cancers, upstream Nodal signaling may represent a promising target for breast cancer diagnosis and combined therapies aimed at blocking ERK pathway activation. PMID:25073112

  2. Nodal signaling promotes a tumorigenic phenotype in human breast cancer

    PubMed Central

    Kirsammer, Gina; Strizzi, Luigi; Margaryan, Naira V.; Gilgur, Alina; Hyser, Matthew; Atkinson, Janis; Kirschmann, Dawn A.; Seftor, Elisabeth A.; Hendrix, Mary J.C.

    2014-01-01

    The Ras-ERK pathway is deregulated in approximately a third of human cancers, particularly those of epithelial origin. In aggressive, triple-negative, basal-like breast cancers, most tumors display increased MEK and ERK phosphorylation and exhibit a gene expression profile characteristic of Kras or EGFR mutant tumors; however, Ras family genetic mutations are uncommon in triple-negative breast cancer and EGFR mutations account for only a subset of these tumors. Therefore, the upstream events that activate MAPK signaling and promote tumor aggression in triple-negative breast cancers remain poorly defined. We have previously shown that a secreted TGF-β family signaling ligand, Nodal, is expressed in breast cancer in correlation with disease progression. Here we highlight key findings demonstrating that Nodal is required in aggressive human breast cancer cells to activate ERK signaling and downstream tumorigenic phenotypes both in vitro and in vivo. Experimental knockdown of Nodal signaling downregulates ERK activity, resulting in loss of c-myc, upregulation of p27, G1 cell cycle arrest, increased apoptosis and decreased tumorigenicity. The data suggest that ERK activation by Nodal signaling regulates c-myc and p27 proteins post-translationally and that this cascade is essential for aggressive breast tumor behavior in vivo. As the MAPK pathway is an important target for treating triple-negative breast cancers, upstream Nodal signaling may represent a promising target for breast cancer diagnosis and combined therapies aimed at blocking ERK pathway activation. PMID:25073112

  3. Pregnancy After Breast Cancer.

    PubMed

    Gemignani; Petrek

    1999-05-01

    BACKGROUND: The issue of pregnancy following the diagnosis and treatment of breast cancer is important because the incidence of breast cancer is increasing in women of childbearing age. The fact that many women are delaying childbearing, whether for educational, professional, or personal reasons, increases the number of women who will undergo breast cancer treatment before completing childbearing. METHODS: Data on pregnancy in breast cancer survivors are limited and consist only of retrospective data. This paper reviews the published literature on the influence of subsequent pregnancy on breast cancer, including three recent large-scale population-based studies. RESULTS: The survival of women with breast carcinoma who subsequently become pregnant is not reported to be decreased in any of the published series. However, several biases may be present that justify the concern regarding the conclusions. CONCLUSIONS: Further research on the safety of subsequent pregnancy after breast carcinoma treatment is needed. To address these issues, patients are currently being accrued for a large, prospective, multicenter study of young breast carcinoma patients. PMID:10758557

  4. Methylxanthines and breast cancer.

    PubMed

    Schairer, C; Brinton, L A; Hoover, R N

    1987-10-15

    We investigated the relationship between methylxanthine consumption and breast cancer using data from a case-control study which included 1,510 cases and 1,882 controls identified through a nation-wide breast cancer screening program. There was no evidence of a positive association between methylxanthine consumption and risk of breast cancer. In fact, there was some suggestion of a negative association, particularly in women diagnosed after age 50. In addition, there was no evidence of increased risk with past or recent methylxanthine consumption, or with the consumption of caffeine or specific beverages, most notably brewed or instant caffeinated coffee and tea. PMID:3117709

  5. Targeting Breast Cancer Metastasis

    PubMed Central

    Jin, Xin; Mu, Ping

    2015-01-01

    Metastasis is the leading cause of breast cancer-associated deaths. Despite the significant improvement in current therapies in extending patient life, 30–40% of patients may eventually suffer from distant relapse and succumb to the disease. Consequently, a deeper understanding of the metastasis biology is key to developing better treatment strategies and achieving long-lasting therapeutic efficacies against breast cancer. This review covers recent breakthroughs in the discovery of various metastatic traits that contribute to the metastasis cascade of breast cancer, which may provide novel avenues for therapeutic targeting. PMID:26380552

  6. Drugs Approved for Breast Cancer

    MedlinePlus

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

  7. Breast Cancer in Young Women

    MedlinePlus

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

  8. Pregnancy and breast cancer

    PubMed Central

    Sasidharan, R; Harvey, V

    2010-01-01

    Breast cancer is one of the most commonly diagnosed malignancies during pregnancy. Pregnancy-associated breast cancer (PABC) presents a challenging clinical situation. This article reviews the current evidence around the management of PABC and the safety of pregnancy after breast cancer. The trend towards later age at first childbirth has resulted in an increase in the number of breast cancer cases coexistent with pregnancy. The management of breast cancer during pregnancy requires a multidisciplinary team approach. Breast surgery can be safely performed during any trimester of pregnancy. Radiation therapy, if required, must be delayed until after delivery. The majority of patients with PABC require chemotherapy. The timing of delivery in relation to chemotherapy administration should be carefully considered. There is no evidence to date that pregnancy termination influences overall survival for the mother. To date, there is no clear evidence that subsequent pregnancy after breast cancer is associated with worse maternal survival. There is a suggestion that subsequent pregnancy may in fact be associated with an improved survival. However, the available studies are limited by potential biases.

  9. Docosahexaenoic Acid in Preventing Recurrence in Breast Cancer Survivors

    ClinicalTrials.gov

    2016-06-20

    Benign Breast Neoplasm; Ductal Breast Carcinoma In Situ; Invasive Breast Carcinoma; Lobular Breast Carcinoma In Situ; Paget Disease of the Breast; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

  10. Broccoli Sprout Extract in Treating Patients With Breast Cancer

    ClinicalTrials.gov

    2016-08-16

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

  11. Breast cancer and protein biomarkers

    PubMed Central

    Gam, Lay-Harn

    2012-01-01

    Breast cancer is a healthcare concern of women worldwide. Despite procedures being available for diagnosis, prognosis and treatment of breast cancer, researchers are working intensively on the disease in order to improve the life quality of breast cancer patients. At present, there is no single treatment known to bring a definite cure for breast cancer. One of the possible solutions for combating breast cancer is through identification of reliable protein biomarkers that can be effectively used for early detection, prognosis and treatments of the cancer. Therefore, the task of identification of biomarkers for breast cancer has become the focus of many researchers worldwide. PMID:24520539

  12. Breast Cancer Surgery

    MedlinePlus

    ... therapy and targeted therapy. This helps to increase survival. Types of breast cancer surgery There are two main types of breast ... shown lumpectomy plus radiation offers the same overall survival benefit as mastectomy for early ... (almost always followed by radiation): The surgeon ...

  13. Hexokinase and phosphofructokinase activity and intracellular distribution correlate with aggressiveness and invasiveness of human breast carcinoma

    PubMed Central

    Coelho, Raquel G.; Calaça, Isadora C.; Celestrini, Deborah M.; Correia-Carneiro, Ana Helena P.; Costa, Mauricio M.; Zancan, Patricia; Sola-Penna, Mauro

    2015-01-01

    Glycolytic enzymes, such as hexokinase and phosphofructokinase, have been reported to be upregulated in many cancer types. Here, we evaluated these two enzymes in 54 breast cancer samples collected from volunteers subjected to mastectomy, and the results were correlated with the prognosis markers commonly used. We found that both enzymes positively correlate with the major markers for invasiveness and aggressiveness. For invasiveness, the enzymes activities increase in parallel to the tumor size. Moreover, we found augmented activities for both enzymes when the samples were extirpated from patients presenting lymph node involvement or occurrence of metastasis. For aggressiveness, we stained the samples for the estrogen and progesterone receptors, HER-2, p53 and Ki-67. The enzyme activities positively correlated with all markers but Ki-67. Finally, we conclude that these enzymes are good markers for breast cancer prognosis. PMID:26320188

  14. General Information about Male Breast Cancer

    MedlinePlus

    ... 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 ...

  15. What Is Breast Cancer in Men?

    MedlinePlus

    ... statistics about breast cancer in men? What is breast cancer in men? A breast cancer is a malignant ... women but are very rare in men. General breast cancer terms Here are some of the key words ...

  16. General Information about Breast Cancer and Pregnancy

    MedlinePlus

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

  17. Treatment Options for Male Breast Cancer

    MedlinePlus

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

  18. Treatment Option Overview (Male Breast Cancer)

    MedlinePlus

    ... 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 ...

  19. Overdiagnosis and overtreatment of breast cancer.

    PubMed

    Alvarado, Michael; Ozanne, Elissa; Esserman, Laura

    2012-01-01

    Breast cancer is the most common cancer in women. Through greater awareness, mammographic screening, and aggressive biopsy of calcifications, the proportion of low-grade, early stage cancers and in situ lesions among all breast cancers has risen substantially. The introduction of molecular testing has increased the recognition of lower risk subtypes, and less aggressive treatments are more commonly recommended for these subtypes. Mammographically detected breast cancers are much more likely to have low-risk biology than symptomatic tumors found between screenings (interval cancers) or that present as clinical masses. Recognizing the lower risk associated with these lesions and the ability to confirm the risk with molecular tests should safely enable the use of less aggressive treatments. Importantly, ductal carcinoma in situ (DCIS) lesions, or what have been called stage I cancers, in and of themselves are not life-threatening. In situ lesions have been treated in a manner similar to that of invasive cancer, but there is little evidence to support that this practice has improved mortality. It is also being recognized that DCIS lesions are heterogeneous, and a substantial proportion of them may in fact be precursors of more indolent invasive cancers. Increasing evidence suggests that these lesions are being overtreated. The introduction of molecular tests should be able to help usher in a change in approach to these lesions. Reclassifying these lesions as part of the spectrum of high-risk lesions enables the use of a prevention approach. Learning from the experience with active surveillance in prostate cancer should empower the introduction of new approaches, with a focus on preventing invasive cancer, especially given that there are effective, United States Food and Drug Administration (FDA)-approved breast cancer preventive interventions. PMID:24451829

  20. PET/CT in Evaluating Response to Chemotherapy in Patients With Breast Cancer

    ClinicalTrials.gov

    2016-04-06

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

  1. Is clinical breast examination important for breast cancer detection?

    PubMed Central

    Provencher, L.; Hogue, J.C.; Desbiens, C.; Poirier, B.; Poirier, E.; Boudreau, D.; Joyal, M.; Diorio, C.; Duchesne, N.; Chiquette, J.

    2016-01-01

    Background Screening clinical breast examination (cbe) is controversial; the use of cbe is declining not only as a screening tool, but also as a diagnostic tool. In the present study, we aimed to assess the value of cbe in breast cancer detection in a tertiary care centre for breast diseases. Methods This retrospective study of all breast cancers diagnosed between July 1999 and December 2010 at our centre categorized cases according to the mean of detection (cbe, mammography, or both). A cbe was considered “abnormal” in the presence of a mass, nipple discharge, skin or nipple retraction, edema, erythema, peau d’orange, or ulcers. Results During the study period, a complete dataset was available for 6333 treated primary breast cancers. Cancer types were ductal carcinoma in situ (15.3%), invasive ductal carcinoma (75.7%), invasive lobular carcinoma (9.0%), or others (2.2%). Of the 6333 cancers, 36.5% (n = 2312) were detected by mammography alone, 54.8% (n = 3470) by mammography and cbe, and 8.7% (n = 551) by physician-performed cbe alone (or 5.3% if considering ultrasonography). Invasive tumours diagnosed by cbe alone were more often triple-negative, her2-positive, node-positive, and larger than those diagnosed by mammography alone (p < 0.05). Conclusions A significant number of cancers would have been missed if cbe had not been performed. Compared with cancers detected by mammography alone, those detected by cbe had more aggressive features. Clinical breast examination is a very low-cost test that could improve the detection of breast cancer and could prompt breast ultrasonography in the case of a negative mammogram. PMID:27536182

  2. Aggressive Metaplastic Carcinoma of the Breast with Osteoclastic Giant Cells

    PubMed Central

    Khong, Kathleen; Zhang, Yanhong; Tomic, Mary; Lindfors, Karen; Aminololama-Shakeri, Shadi

    2015-01-01

    Metaplastic carcinoma of the breast is an uncommon type of malignancy that is aggressive but can mimic other benign breast neoplastic processes on imaging. We present a case of a young female patient who presented with a rapidly progressing metaplastic carcinoma with osteoclastic giant cells subtype. There have been only very rare published reports of this pathologic subtype of metaplastic carcinoma containing osteoclastic giant cells. PMID:26629304

  3. Tibolone and breast cancer

    PubMed Central

    Erel, C Tamer; Senturk, Levent M; Kaleli, Semih

    2006-01-01

    Tibolone is a relatively new drug for postmenopausal women, which is structurally related to 19‐nortestosterone derivatives and exhibits weak oestrogenic, progestogenic and androgenic activities. The effect of tibolone on breast tissue is still obscure. In vitro studies have shown conflicting results regarding the effects of tibolone on breast cells. On the other hand, although epidemiological studies show an increase in the risk of breast cancer among women treated with tibolone, accumulation of data obtained from radiological studies presents promising results. However, the safety of tibolone with regard to breast tissue needs to be investigated further, especially through well‐designed, large‐scale, randomised‐controlled trials. PMID:17068276

  4. Synchronous Bilateral Breast Cancers

    PubMed Central

    Subramanyan, Annapurneswari; Radhakrishna, Selvi

    2015-01-01

    Background Bilateral breast cancer (BBC) is not an uncommon entity in contemporary breast clinics. Improved life expectancy after breast cancer treatment and routine use of contra-lateral breast mammography has led to increased incidence of BBC. Our study objective was to define the epidemiological and tumour characteristics of BBC in India. Materials and Methods A total of 1251 breast cancer patients were treated during the period January 2007 to March 2015 and 30 patients were found to have BBC who constituted the study population (60 tumour samples). Synchronous bilateral breast cancers (SBC) was defined as two tumours diagnosed within an interval of 6 months and a second cancer diagnosed after 6 months was labelled as metachronous breast cancer (MBC). Analyses of patient and tumour characteristics were done in this prospective data base of BBC patients. Results Median patient age was 66 years (range 39-85). Majority of the patients had SBC (n=28) and in 12 patients the second tumour was clinically occult and detected only by mammography of the contra-lateral breast. The second tumour was found at lower tumour size compared to the first in 73% of cases and was negative for axillary metastasis in 80% of cases (24/30). Infiltrating ductal carcinoma was the commonest histological type (n=51) and majority of the tumours were ER/PR positive (50/60). Her2 was overexpressed in 13 tumours (21%). Over 70% (22/30) of patients had similar histology in both breasts and amongst them grade concordance was present in about 69% (15/22) of patients. Concordance rates of ER, PR and Her2 statuses were 83%, 80% and 90% respectively. Bilateral mastectomy was the commonest surgery performed in 80% of the patients followed by bilateral breast conservation in 13%. At the end of study period, 26 patients were alive and disease free. Median survival was 29 months (range 3-86 months). Conclusion In most patients with BBC, the second tumour is identified at an early stage than index

  5. Human Breast Cancer Histoid

    PubMed Central

    Kaur, Pavinder; Ward, Brenda; Saha, Baisakhi; Young, Lillian; Groshen, Susan; Techy, Geza; Lu, Yani; Atkinson, Roscoe; Taylor, Clive R.; Ingram, Marylou

    2011-01-01

    Progress in our understanding of heterotypic cellular interaction in the tumor microenvironment, which is recognized to play major roles in cancer progression, has been hampered due to unavailability of an appropriate in vitro co-culture model. The aim of this study was to generate an in vitro 3-dimensional human breast cancer model, which consists of cancer cells and fibroblasts. Breast cancer cells (UACC-893) and fibroblasts at various densities were co-cultured in a rotating suspension culture system to establish co-culture parameters. Subsequently, UACC-893, BT.20, or MDA.MB.453 were co-cultured with fibroblasts for 9 days. Co-cultures resulted in the generation of breast cancer histoid (BCH) with cancer cells showing the invasion of fibroblast spheroids, which were visualized by immunohistochemical (IHC) staining of sections (4 µm thick) of BCH. A reproducible quantitative expression of C-erbB.2 was detected in UACC-893 cancer cells in BCH sections by IHC staining and the Automated Cellular Imaging System. BCH sections also consistently exhibited qualitative expression of pancytokeratins, p53, Ki-67, or E-cadherin in cancer cells and that of vimentin or GSTPi in fibroblasts, fibronectin in the basement membrane and collagen IV in the extracellular matrix. The expression of the protein analytes and cellular architecture of BCH were markedly similar to those of breast cancer tissue. PMID:22034518

  6. Viruses and Breast Cancer

    PubMed Central

    Lawson, James S.; Heng, Benjamin

    2010-01-01

    Viruses are the accepted cause of many important cancers including cancers of the cervix and anogenital area, the liver, some lymphomas, head and neck cancers and indirectly human immunodeficiency virus associated cancers. For over 50 years, there have been serious attempts to identify viruses which may have a role in breast cancer. Despite these efforts, the establishment of conclusive evidence for such a role has been elusive. However, the development of extremely sophisticated new experimental techniques has allowed the recent development of evidence that human papilloma virus, Epstein-Barr virus, mouse mammary tumor virus and bovine leukemia virus may each have a role in the causation of human breast cancers. This is potentially good news as effective vaccines are already available to prevent infections from carcinogenic strains of human papilloma virus, which causes cancer of the uterine cervix. PMID:24281093

  7. Breast cancer in adolescent and young adult women.

    PubMed

    Gewefel, Hanan; Salhia, Bodour

    2014-12-01

    Breast cancer is one of the most frequently diagnosed malignancy among adolescent and young adult (AYA) women, accounting for approximately 14% of all AYA cancer diagnoses and 7% of all breast cancer. Breast cancer in AYA women is believed to represent a more biologically aggressive disease, but aside from commonly known hereditary predispositions, little is still known about the underlying molecular genetic causes. This review examines the current trends of breast cancer in AYA women as they relate to clinical, social, genetic, and molecular pathologic characteristics. We highlight existing trends, treatment and imaging approaches, and health burdens as they relate to breast cancer in AYA women and provide a discussion on ways to help improve the overall management of this breast cancer cohort. PMID:25034440

  8. Breast Cancer Detection

    NASA Technical Reports Server (NTRS)

    2000-01-01

    The BioScan System was developed by OmniCorder Technologies, Inc. at the Jet Propulsion Laboratory. The system is able to locate cancerous lesions by detecting the cancer's ability to recruit a new blood supply. A digital sensor detects infrared energy emitted from the body and identifies the minute differences accompanying the blood flow changes associated with cancerous cells. It also has potential use as a monitoring device during cancer treatment. This technology will reduce the time taken to detect cancerous cells and allow for earlier intervention, therefore increasing the overall survival rates of breast cancer patients.

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

    ClinicalTrials.gov

    2015-08-27

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

  10. Breast Cancer Screening.

    PubMed

    Euhus, David; Di Carlo, Philip A; Khouri, Nagi F

    2015-10-01

    Breast cancer screening has become a controversial topic. Understanding the points of contention requires an appreciation of the conceptual framework underpinning cancer screening in general, knowledge of the strengths and limitations of available screening modalities, and familiarity with published clinical trial data. This review is data intense with the intention of presenting enough information to permit the reader to enter into the discussion with an ample knowledge base. The focus throughout is striking a balance between the benefits and harms of breast cancer screening. PMID:26315519

  11. Preventing Breast Cancer: Making Progress

    MedlinePlus

    Skip Navigation Bar Home Current Issue Past Issues Preventing Breast Cancer: Making Progress Past Issues / Fall 2006 Table of ... inhibitor, can do an even better job of preventing breast cancer than the SERMs. Aromatase inhibitors stop an enzyme ...

  12. Treatment Option Overview (Breast Cancer)

    MedlinePlus

    ... to treat breast cancer. Internal radiation therapy with strontium-89 (a radionuclide ) is used to relieve bone pain ... breast cancer that has spread to the bones. Strontium-89 is injected into a vein and travels to ...

  13. 'Ppl, I Have Breast Cancer'

    MedlinePlus

    ... gov/news/fullstory_160134.html 'Ppl, I Have Breast Cancer' Many women found online support after their diagnosis, ... Women who communicated via social media after a breast cancer diagnosis and received information and/or support about ...

  14. Life After Breast Cancer Treatment

    MedlinePlus

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

  15. Grading Breast Cancer Tissues Using Molecular Portraits*

    PubMed Central

    Olsson, Niclas; Carlsson, Petter; James, Peter; Hansson, Karin; Waldemarson, Sofia; Malmström, Per; Fernö, Mårten; Ryden, Lisa; Wingren, Christer; Borrebaeck, Carl A. K.

    2013-01-01

    Tumor progression and prognosis in breast cancer patients are difficult to assess using current clinical and laboratory parameters, where a pathological grading is indicative of tumor aggressiveness. This grading is based on assessments of nuclear grade, tubule formation, and mitotic rate. We report here the first protein signatures associated with histological grades of breast cancer, determined using a novel affinity proteomics approach. We profiled 52 breast cancer tissue samples by combining nine antibodies and label-free LC-MS/MS, which generated detailed quantified proteomic maps representing 1,388 proteins. The results showed that we could define in-depth molecular portraits of histologically graded breast cancer tumors. Consequently, a 49-plex candidate tissue protein signature was defined that discriminated between histological grades 1, 2, and 3 of breast cancer tumors with high accuracy. Highly biologically relevant proteins were identified, and the differentially expressed proteins indicated further support for the current hypothesis regarding remodeling of the tumor microenvironment during tumor progression. The protein signature was corroborated using meta-analysis of transcriptional profiling data from an independent patient cohort. In addition, the potential for using the markers to estimate the likelihood of long-term metastasis-free survival was also indicated. Taken together, these molecular portraits could pave the way for improved classification and prognostication of breast cancer. PMID:23982162

  16. Minimally Invasive Treatments for Breast Cancer

    MedlinePlus

    ... SIR login) Interventional Radiology Minimally Invasive Treatments for Breast Cancer Interventional Radiology Treatments Offer New Options and Hope ... have in the fight against breast cancer. About Breast Cancer When breast tissue divides and grows at an ...

  17. Computerized Cognitive Retraining in Improving Cognitive Function in Breast Cancer Survivors

    ClinicalTrials.gov

    2016-08-26

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

  18. Could Certain Fatty Foods Be Linked to Aggressive Prostate Cancer?

    MedlinePlus

    ... html Could Certain Fatty Foods Be Linked to Aggressive Prostate Cancer? Study also suggests that cholesterol-lowering ... fatty beef and cheese was linked with more aggressive prostate cancer, the researchers found. A diet high ...

  19. Low Vitamin D Levels May Signal More Aggressive Prostate Cancer

    MedlinePlus

    ... html Low Vitamin D Levels May Signal More Aggressive Prostate Cancer But men should not expect supplements ... 2016 (HealthDay News) -- Prostate cancer may be more aggressive in men who are deficient in vitamin D, ...

  20. The immune system and inflammation in breast cancer

    PubMed Central

    Jiang, Xinguo; Shapiro, David J.

    2016-01-01

    During different stages of tumor development the immune system can either identify and destroy tumors, or promote their growth. Therapies targeting the immune system have emerged as a promising treatment modality for breast cancer, and immunotherapeutic strategies are being examined in preclinical and clinical models. However, our understanding of the complex interplay between cells of the immune system and breast cancer cells is incomplete. In this article, we review recent findings showing how the immune system plays dual host-protective and tumor-promoting roles in breast cancer initiation and progression. We then discuss estrogen receptor α (ERα)-dependent and ERα-independent mechanisms that shield breast cancers from immunosurveillance and enable breast cancer cells to evade immune cell induced apoptosis and produce an immunosuppressive tumor microenvironment. Finally, we discuss protumorigenic inflammation that is induced during tumor progression and therapy, and how inflammation promotes more aggressive phenotypes in ERα positive breast cancers. PMID:23791814

  1. Diet and breast cancer.

    PubMed

    Bradlow, H Leon; Sepkovic, Daniel W

    2002-06-01

    The preponderance of evidence suggests a role for fat and alcohol as risk factors for breast cancer. The role of milk is more controversial with some studies suggesting that milk is a risk factor and others that consumption of milk is protective against breast cancer. No other major nutrient appears to play a significant role in increasing breast cancer risk. On the other hand, there is increasing evidence that a variety of micronutrients and hormones appear to have significant anticancer activity. These range from steroids such as dehydroepiandrosterone (DHEA) and its analysis to indoles, isothiocyanates, and isoflavone derivatives. These compounds act directly by interfering with cyclins and promoting apoptosis as well as indirectly by altering estrogen metabolism in a favorable direction. These effects are not merely theoretical actions in cell culture and tissue explants; they have been demonstrated in human patients as a range of studies have demonstrated. PMID:12095951

  2. Cryosurgery of breast cancer

    PubMed Central

    Zhou, Liang; Xu, Kecheng

    2012-01-01

    With recent improvements in breast imaging, the ability to identify small breast tumors is markedly improved, prompting significant interest in the use of cryoablation without surgical excision to treat early-stage breast cancer. The cryoablation is often performed using ultrasound-guided tabletop argon-gas-based cryoablation system with a double freeze/thaw cycle. Recent studies have demonstrated that, as a primary therapy for small breast cancer, cryoablation is safe and effective with durable results, and can successfully destroy all cancers <1.0 cm and tumors between 1.0 and 1.5 cm without a significant ductal carcinoma-in-situ (DCIS) component. Presence of noncalcified DCIS is the cause of most cryoablation failures. At this time, cryoablation should be limited to patients with invasive ductal carcinoma <1.5 cm and with <25% DCIS in the core biopsy. For unresectable advanced breast cancer, cryoablation is a palliation modality and may be used as complementary for subsequent resection or other therapies. PMID:25083433

  3. Surgery for breast cancer.

    PubMed

    Dooley, W C

    1998-11-01

    Women with breast cancer today have many more therapeutic options available to them for their surgical therapy. Almost all patients with breast cancer have some options for breast conservation. Active patient involvement in analyzing and understanding the pros and cons of each of these options seems extremely important to the long-term emotional and psychological outcome of their breast cancer therapy. Several reports this year have reintroduced the issue of adequate local control. The common philosophy a decade ago was that because systematic therapy (adjuvant chemotherapy) was improving, local therapy would become of lesser importance. Several studies this year have indicated the extreme importance of local control in maximizing survival advantage because of the relationship of increasing local failure and deteriorating survival from systemic disease. Despite significant improvements in treatment, our screening and diagnostic approaches have still failed to identify the majority of lesions prior to the patient's own palpation of the tumor. Using new diagnostic modalities that do not involve surgery, the biopsy of lower probability lesions with great accuracy is expected to improve the efficacy of the current screening measures. Despite all the improvements, the most important therapeutic step in the management of breast cancer remains earlier diagnosis and earlier extirpation of the initial invasive focus of malignancy. PMID:9818228

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

    ClinicalTrials.gov

    2016-03-17

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

  5. Breast cancer following augmentation mammaplasty with polyacrylamide hydrogel (PAAG) injection.

    PubMed

    Cheng, Ning-Xin; Liu, Li-Gang; Hui, Li; Chen, Yuan-Liang; Xu, Shi-Liang

    2009-07-01

    Polyacrylamide hydrogel (PAAG) as an implanted material for augmentation mammaplasty has been used for years in China. Many kinds of complications associated with PAAG use have been reported in the clinical literature. This report presents two cases of breast cancer occurring after injection of PAAG in augmented breasts. The delayed diagnosis and more aggressive disease due to PAAG injection should be cause for concern. It is very important to detect breast cancer early when it is covered by the induration of the injected gel and inflammation reaction after PAAG injection. PAAG injection for augmentation mammaplasty may affect the outcome of breast cancer diagnosis and prognosis. PMID:19156460

  6. Methylated APC and GSTP1 genes in serum DNA correlate with the presence of circulating blood tumor cells and are associated with a more aggressive and advanced breast cancer disease

    PubMed Central

    2010-01-01

    significantly correlated with positive Her2/neu status (p = 0.003). Elevated serum CA15.3 was strongly correlated with methylated APC and CTC detection (both p = 0.000). Methylated ESR1 failed to exhibit significant correlations with any of the above mentioned parameters. The presence of CTC in peripheral blood was significantly associated with methylated APC (p = 0.012) and methylated GSTP1 (p = 0.001). Conclusion The detection of methylated APC and GSTP1 DNA in serum correlated with the presence of CTC in the blood of breast cancer patients. Both methylated DNA and CTC correlated with a more aggressive tumor biology and advanced disease. PMID:20696638

  7. The role of lipolysis stimulated lipoprotein receptor in breast cancer and directing breast cancer cell behavior.

    PubMed

    Reaves, Denise K; Fagan-Solis, Katerina D; Dunphy, Karen; Oliver, Shannon D; Scott, David W; Fleming, Jodie M

    2014-01-01

    The claudin-low molecular subtype of breast cancer is of particular interest for clinically the majority of these tumors are poor prognosis, triple negative, invasive ductal carcinomas. Claudin-low tumors are characterized by cancer stem cell-like features and low expression of cell junction and adhesion proteins. Herein, we sought to define the role of lipolysis stimulated lipoprotein receptor (LSR) in breast cancer and cancer cell behavior as LSR was recently correlated with tumor-initiating features. We show that LSR was expressed in epithelium, endothelium, and stromal cells within the healthy breast tissue, as well as in tumor epithelium. In primary breast tumor bioposies, LSR expression was significantly correlated with invasive ductal carcinomas compared to invasive lobular carcinomas, as well as ERα positive tumors and breast cancer cell lines. LSR levels were significantly reduced in claudin-low breast cancer cell lines and functional studies illustrated that re-introduction of LSR into a claudin-low cell line suppressed the EMT phenotype and reduced individual cell migration. However, our data suggest that LSR may promote collective cell migration. Re-introduction of LSR in claudin-low breast cancer cell lines reestablished tight junction protein expression and correlated with transepithelial electrical resistance, thereby reverting claudin-low lines to other intrinsic molecular subtypes. Moreover, overexpression of LSR altered gene expression of pathways involved in transformation and tumorigenesis as well as enhanced proliferation and survival in anchorage independent conditions, highlighting that reestablishment of LSR signaling promotes aggressive/tumor initiating cell behaviors. Collectively, these data highlight a direct role for LSR in driving aggressive breast cancer behavior. PMID:24637461

  8. Inflammatory Breast Cancer from Metastatic Ovarian Cancer

    PubMed Central

    Achariyapota, Vuthinun; Chuangsuwanich, Tuenjai

    2016-01-01

    Metastases to the breast from tumors other than breast carcinomas are extremely rare and represent only 0.2–1.3% of all diagnosed malignant breast tumors. Furthermore, while the most common sites for advanced ovarian cancer metastases are the liver, lung, and pleura, metastasis to the breast from a primary ovarian cancer is uncommon and has only been reported in 0.03–0.6% of all breast cancers. Here we describe a case report of a 50-year-old female patient with a rare case of breast metastases from an advanced ovarian cancer, presenting as inflammatory breast cancer. Our observations emphasize the clinical importance of distinguishing between primary and metastatic breast cancer during diagnosis for the purpose of appropriate prognosis and treatment. PMID:27047697

  9. Vitamin D and Breast Cancer

    PubMed Central

    Klein, Paula; Grossbard, Michael L.

    2012-01-01

    In addition to its role in calcium homeostasis and bone health, vitamin D has also been reported to have anticancer activities against many cancer types, including breast cancer. The discovery that breast epithelial cells possess the same enzymatic system as the kidney, allowing local manufacture of active vitamin D from circulating precursors, makes the effect of vitamin D in breast cancer biologically plausible. Preclinical and ecologic studies have suggested a role for vitamin D in breast cancer prevention. Inverse associations have also been shown between serum 25-hydroxyvitamin D level (25(OH)D) and breast cancer development, risk for breast cancer recurrence, and mortality in women with early-stage breast cancer. Clinical trials of vitamin D supplementation, however, have yielded inconsistent results. Regardless of whether or not vitamin D helps prevent breast cancer or its recurrence, vitamin D deficiency in the U.S. population is very common, and the adverse impact on bone health, a particular concern for breast cancer survivors, makes it important to understand vitamin D physiology and to recognize and treat vitamin D deficiency. In this review, we discuss vitamin D metabolism and its mechanism of action. We summarize the current evidence of the relationship between vitamin D and breast cancer, highlight ongoing research in this area, and discuss optimal dosing of vitamin D for breast cancer prevention. PMID:22234628

  10. Virtual Weight Loss Program in Maintaining Weight in African American Breast Cancer Survivors

    ClinicalTrials.gov

    2016-09-01

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

  11. [Breast cancer imaging].

    PubMed

    Canale, Sandra; Balleyguier, Corinne; Dromain, Clarisse

    2013-12-01

    Imaging of breast cancer is multimodal. Mammography uses X-rays, the development of digital mammography has improved its quality and enabled implementations of new technologies such astomosynthesis (3D mammography) or contrast-enhanced digital mammography. Ultrasound is added to mammography when there is need to improve detection in high-density breast, to characterize an image, or guide apuncture or biopsy. Breast MRI is the most sensitive imaging modality. It detects a possible tumor angiogenesis by highlighting an early and intense contrast uptake. This method has an excellent negative predictive value, but its lack of specificity (false positives) can be problematic, thus it has to be prescribed according to published standards. An imaging breast screening report must be concluded by the BI-RADS lexicon classification of the ACR and recommendations about monitoring or histological verification. PMID:24579332

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

    ClinicalTrials.gov

    2016-03-16

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

  13. Novel highly specific anti-periostin antibodies uncover the functional importance of the fascilin 1-1 domain and highlight preferential expression of periostin in aggressive breast cancer.

    PubMed

    Field, Sarah; Uyttenhove, Catherine; Stroobant, Vincent; Cheou, Paméla; Donckers, Dominique; Coutelier, Jean-Paul; Simpson, Peter T; Cummings, Margaret C; Saunus, Jodi M; Reid, Lynne E; Kutasovic, Jamie R; McNicol, Anne Marie; Kim, Ba Reun; Kim, Jae Ho; Lakhani, Sunil R; Neville, A Munro; Van Snick, Jacques; Jat, Parmjit S

    2016-04-15

    Periostin (POSTN), a secreted homodimeric protein that binds integrins αvβ3, αvβ5, and α6β4, was originally found to be expressed in fetal tissues and in the adult upon injury particularly bone fractures due to its role in remodelling and repair. Recently it was found to be over-expressed in human breast cancer and a variety of other tumour types including head and neck squamous cell carcinoma, where its overexpression correlates with increased tumour invasion. Progress in studying its functional role in tumour pathogenesis has been hampered by the paucity of antibodies for its specific and sensitive detection. It has proven very difficult to obtain monoclonal antibodies (mAbs) against this highly conserved protein but we report here that combining infection of mice with lactate dehydrogenase elevating virus (LDV), a B cell activating arterivirus, with conjugation of human POSTN to ovalbumin as an immunogenic carrier, enabled us to develop six mAbs recognizing both human and mouse POSTN and inhibiting its binding to αvβ3 integrin. Two of the mAbs, MPB4B1 and MPC5B4, were tested and found to inhibit POSTN-induced migration of human endothelial colony forming cells. All six mAbs recognized amino acids 136-51 (APSNEAWDNLDSDIRR) within the POSTN fascilin (FAS) 1-1 domain revealing the functional importance of this motif; this was further highlighted by the ability of aa 136-151 peptide to inhibit integrin-mediated cell migration. Immunohistochemistry using MPC5B4, indicated that breast tumour cell POSTN expression was a strong prognostic indicator, along with tumour size, lymph node, and human epidermal growth factor receptor 2 (HER2) status. PMID:26619948

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

    PubMed

    Dean, S J R; Rhodes, A

    2014-12-01

    The incidence of breast cancer in Malaysia and other Asian countries is on the increase, reflecting lifestyle changes some of which are known risk factors for the development of breast cancer. Most breast cancers are amenable to adjuvant therapies that target hormone receptors or HER2 receptors on the surface of the cancer cells and bring about significant improvement in survival. However, approximately 17% of Malaysian women with breast cancer, present with tumours that are devoid of these receptors and are consequently termed 'triple negative' breast cancers. These triple negative breast cancers typically occur in women of a younger age than receptor positive cancers, are predominantly of high grade tumours and the prognosis is usually poor. There is therefore a pressing need to understand the biological pathways that drive these tumours, in order that effective strategies are developed to treat these aggressive tumours. With the increasing affluence of developing countries, obesity and Type II Diabetes are also on the rise. These diseases are associated with an increased risk of developing a range of cancers including those of the breast. In particular, the metabolic syndrome has been shown to be associated with triple negative breast cancer. This article reviews some of the metabolic pathways and biomarkers which have been shown to be aberrantly expressed in triple negative breast cancer and highlights some of the ongoing work in this area. PMID:25500513

  15. Progestins and breast cancer.

    PubMed

    Pasqualini, Jorge R

    2007-10-01

    Progestins exert their progestational activity by binding to the progesterone receptor (form A, the most active and form B, the less active) and may also interact with other steroid receptors (androgen, glucocorticoid, mineralocorticoid, estrogen). They can have important effects in other tissues besides the endometrium, including the breast, liver, bone and brain. The biological responses of progestins cover a very large domain: lipids, carbohydrates, proteins, water and electrolyte regulation, hemostasis, fibrinolysis, and cardiovascular and immunological systems. At present, more than 200 progestin compounds have been synthesized, but the biological response could be different from one to another depending on their structure, metabolism, receptor affinity, experimental conditions, target tissue or cell line, as well as the biological response considered. There is substantial evidence that mammary cancer tissue contains all the enzymes responsible for the local biosynthesis of estradiol (E(2)) from circulating precursors. Two principal pathways are implicated in the final steps of E(2) formation in breast cancer tissue: the 'aromatase pathway', which transforms androgens into estrogens, and the 'sulfatase pathway', which converts estrone sulfate (E(1)S) into estrone (E(1)) via estrone sulfatase. The final step is the conversion of weak E(1) to the potent biologically active E(2) via reductive 17beta-hydroxysteroid dehydrogenase type 1 activity. It is also well established that steroid sulfotransferases, which convert estrogens into their sulfates, are present in breast cancer tissues. It has been demonstrated that various progestins (e.g. nomegestrol acetate, medrogestone, promegestone) as well as tibolone and their metabolites can block the enzymes involved in E(2) bioformation (sulfatase, 17beta-hydroxysteroid dehydrogenase) in breast cancer cells. These substances can also stimulate the sulfotransferase activity which converts estrogens into the biologically

  16. Surveying Breast Cancer's Genomic Landscape.

    PubMed

    2016-07-01

    An in-depth analysis has produced the most comprehensive portrait to date of the myriad genomic alterations involved in breast cancer. In sequencing the whole genomes of 560 breast cancers and combining this information with published data from another 772 breast tumors, the research team uncovered several new genes and mutational signatures that potentially influence this disease. PMID:27225883

  17. Breast Cancer Research at NASA

    NASA Technical Reports Server (NTRS)

    1998-01-01

    Dr. Harry Mahtani analyzes the gas content of nutrient media from Bioreactor used in research on human breast cancer. NASA's Marshall Space Flight Center (MSFC) is sponsoring research with Bioreactors, rotating wall vessels designed to grow tissue samples in space, to understand how breast cancer works. This ground-based work studies the growth and assembly of human mammary epithelial cells (HMEC) from breast cancer susceptible tissue. Radiation can make the cells cancerous, thus allowing better comparisons of healthy vs. tunourous tissues.

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

    ClinicalTrials.gov

    2016-06-23

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

  19. Breast cancer surveillance.

    PubMed

    Rachetta, Eleonora; Osano, Silvia; Astegiano, Francesco; Martincich, Laura

    2016-10-01

    Since several studies have demonstrated the inadequate diagnostic performance of mammography in high risk women, over the past two decades, different breast imaging tests have been evaluated as additional diagnostic methods to mammography, and the most relevant ones are the techniques that do not imply the use of X-rays, considering the young age of these patients and the higher radio-sensitivity. Breast dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) has risen growing interest not only because of the absence of use of X-rays, but also because it provides morpho-functional features, which may depict biological characteristics of breast tissues, including invasive and in situ cancers. Different multicenter non-randomized prospective studies aimed to evaluate breast DCE-MRI as an integral part of surveillance programs, agreed about the evidence that in high risk women screening with DCE-MRI is more effective than either mammography and/or ultrasound. Moreover, this modality leads to the identifications of cancers at a more favorable stage, allowing a real advantage in terms of tumor size and nodal involvement. The medical community is evaluating to suggest DCE-MRI alone as screening modality in high-risk women, as it was reported that in these cases the sensitivity of MRI plus conventional imaging was not significantly higher than that of MRI alone. Breast MRI is now recommended as part of screening program for high risk women by both European and American guidelines. PMID:26924173

  20. Your Body After Breast Cancer

    MedlinePlus

    ... from a trained breast cancer survivor. Cancer Survivors Network : An online community of people with cancer and their loved ones that provides peer support through discussion boards, chat rooms and other ...

  1. Reproduction after breast cancer.

    PubMed

    Zervoudis, Stefanos; Iatrakis, George; Navrozoglou, Iordanis

    2010-02-01

    Breast cancer is the most frequently occurring cancer in women of developed countries, and as a result of new developments in breast cancer treatment, more women are cured after being diagnosed with this disease. It is important that fertility preservation strategies are addressed before chemotherapy, because chemotherapy may induce premature ovarian failure (depending on the woman's age, the drugs used, the dosage and duration of treatment). Among possible solutions are embryos or oocytes cryopreservation, ovarian tissue cryopreservation-freezing with a subsequent orthotopic and heterotopic autotransplantation, whole ovary cryopreservation, ovarian suppression with gonadotropin-releasing hormone (GnRH) analogues, which inhibit ovarian follicular depletion induced by chemotherapeutic agents and in vitro fertilisation (IVF) after ovulation induction with aromatase inhibitors or tamoxifen. PMID:20170848

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

    PubMed Central

    Pfeiffer, Ruth M.; Miglioretti, Diana L.; Kerlikowske, Karla; Tice, Jeffery; Vacek, Pamela M.; Gierach, Gretchen L.

    2016-01-01

    women counseling, it may be useful to note that high predicted risk of developing breast cancer does not imply that if cancer develops it will behave aggressively. PMID:27560501

  3. Weekly Paclitaxel/Carboplatin/Trastuzumab Therapy Improves Pathologic Complete Remission in Aggressive HER2-Positive Breast Cancers, Especially in Luminal-B Subtype, Compared With a Once-Every-3-Weeks Schedule

    PubMed Central

    Yu, Ke-Da; Liu, Guang-Yu; Chen, Can-Ming; Li, Jian-Wei; Wu, Jiong; Lu, Jin-Song; Shen, Zhen-Zhou

    2013-01-01

    Background. The efficacy and tolerability of two different schedules of paclitaxel, carboplatin, and trastuzumab (PCarH) for HER2-positive, locally aggressive (stage IIB–IIIC) breast cancers were evaluated in this phase II trial. Methods. Patients were randomly assigned to receive either weekly (12 doses over 16 weeks) or once-every-3-weeks (4 doses over 12 weeks) treatment. The primary endpoint was pathologic complete remission (pCR) in the breast and axilla. To detect an assumed 35% pCR absolute difference between the two schedules, a minimum of 26 assessable patients in each group was required (two-sided α = 0.05, β = 0.2). Results. A total of 56 patients were enrolled (weekly group, n = 29; every-3-weeks group, n = 27). In the intent-to-treat analysis, pCR in the breast/axilla were found in 31 patients (55%; 95% confidence interval [CI]: 41%–69%). Compared with the every-3-weeks schedule, the weekly administration achieved higher pCR (41% vs. 69%; p = .03). After adjustment for clinical and pathological factors, the weekly administration was more effective than the every-3-weeks schedule, with hazard ratio of 0.3 (95% CI: 0.1–0.9; p = .03). Interestingly, weekly administration resulted in high pCR rates in both luminal-B (HER2-positive) and ERBB2+ tumors (67% vs. 71%; p = .78), whereas luminal-B (HER2-positive) tumors benefited less from the every-3-weeks schedule compared with the ERBB2+ tumors (21% vs. 62%, p = .03). These results remain after multivariate adjustment, showing weekly administration was more effective in the luminal-B (HER2-positive) subgroup (p = .02) but not in the ERBB2+ subgroup (p = .50). Conclusion. A more frequent administration might improve the possibility of eradicating invasive cancer in the breast and axilla, especially in the luminal-B (HER2-positive) subtype. Further studies to validate our findings are warranted. PMID:23635560

  4. NIH scientists identify molecular link between metabolism and breast cancer

    Cancer.gov

    A protein associated with conditions of metabolic imbalance, such as diabetes and obesity, may play a role in the development of aggressive forms of breast cancer, according to new findings by researchers at the National Cancer Institute (NCI), part of th

  5. African American women's perspectives on breast cancer: implications for communicating risk of basal-like breast cancer.

    PubMed

    Allicock, Marlyn; Graves, Neasha; Gray, Kathleen; Troester, Melissa A

    2013-05-01

    African American women suffer a disproportionately high burden of basal-like breast cancer, an aggressive subtype that has no targeted therapy. While epidemiologic research has identified key prevention strategies, little is known about how best to communicate risk to this population. This study explored women's knowledge, beliefs, and attitudes about breast cancer to learn about risk perceptions. Six focus groups were conducted in North Carolina with 57 women (ages 18-49). Age, race (especially perceptions of cancer as a "White disease"), and lack of family history of breast cancer were all shown to contribute to women's perceptions of low breast cancer susceptibility. Perceptions of low risk were also attributed to conflicting risk information from family, media, and health providers. Women had little to no knowledge of breast cancer subtypes, and emphasized that health communications should be personally relevant, culturally appropriate, and convenient. These findings will assist in developing health communication tools that encourage prevention. PMID:23728042

  6. Cochrane review on screening for breast cancer with mammography.

    PubMed

    Olsen, O; Gøtzsche, P C

    2001-10-20

    In 2000, we reported that there is no reliable evidence that screening for breast cancer reduces mortality. As we discuss here, a Cochrane review has now confirmed and strengthened our previous findings. The review also shows that breast-cancer mortality is a misleading outcome measure. Finally, we use data supplemental to those in the Cochrane review to show that screening leads to more aggressive treatment. PMID:11684218

  7. Azacitidine in Treating Patients With Triple Negative Stage I-IV Invasive Breast Cancer That Can Be Removed By Surgery

    ClinicalTrials.gov

    2014-02-05

    Recurrent Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer; Triple-negative Breast Cancer

  8. What's New in Breast Cancer Research and Treatment?

    MedlinePlus

    ... References: Breast cancer detailed guide What`s new in breast cancer research and treatment? Researchers around the world are ... for breast cancer Breast cancer treatment Causes of breast cancer Studies continue to uncover lifestyle factors and habits, ...

  9. Pharmacokinetically Guided Everolimus in Patients With Breast Cancer, Pancreatic Neuroendocrine Tumors, or Kidney Cancer

    ClinicalTrials.gov

    2016-01-12

    Estrogen Receptor-positive Breast Cancer; Gastrinoma; Glucagonoma; HER2-negative Breast Cancer; Insulinoma; Mucositis; Oral Complications; Pancreatic Polypeptide Tumor; Progesterone Receptor-positive Breast Cancer; Recurrent Breast Cancer; Recurrent Islet Cell Carcinoma; Recurrent Renal Cell Cancer; Somatostatinoma; Stage III Renal Cell Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer; Stage IV Renal Cell Cancer

  10. You, Your Teenage Daughter and Breast Cancer.

    ERIC Educational Resources Information Center

    Brateman, Libby

    1991-01-01

    Discusses breast cancer and teenagers, focusing on how parents can introduce the subject and encourage breast self-examination. The article provides information on breast cancer statistics, mammography, and American Cancer Society services. (SM)

  11. Surgery for Breast Cancer in Men

    MedlinePlus

    ... therapy for breast cancer in men Surgery for breast cancer in men The thought of surgery can be ... 2 to 3 hours. What to expect after breast cancer surgery: After your surgery, you will be taken ...

  12. Reproduction and Breast Cancer Risk

    PubMed Central

    Hanf, Volker; Hanf, Dorothea

    2014-01-01

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

  13. Researchers Find 8 Immune Genes in Aggressive Brain Cancer

    MedlinePlus

    ... 159031.html Researchers Find 8 Immune Genes in Aggressive Brain Cancer Discovery might eventually lead to better ... tissue samples from 170 people with a less aggressive type of brain tumor. This led to the ...

  14. Extensive Surgery Best for an Aggressive Brain Cancer

    MedlinePlus

    ... 159415.html Extensive Surgery Best for an Aggressive Brain Cancer: Study Although larger procedure carries more risk, ... comes to battling a particularly aggressive form of brain tumor, more extensive surgeries may be best to ...

  15. Extensive Surgery Best for an Aggressive Brain Cancer

    MedlinePlus

    ... fullstory_159415.html Extensive Surgery Best for an Aggressive Brain Cancer: Study Although larger procedure carries more ... News) -- When it comes to battling a particularly aggressive form of brain tumor, more extensive surgeries may ...

  16. Chemoprevention for breast cancer.

    PubMed

    Bozovic-Spasojevic, I; Azambuja, E; McCaskill-Stevens, Worta; Dinh, P; Cardoso, F

    2012-08-01

    Despite the progress that has been made in breast cancer diagnosis and treatment, this disease is still a major health problem, being the most frequently diagnosed cancer and the first leading cause of cancer death among women both in developed and economically developing countries. In some developed countries incidence rate start to decrease from the end of last millennium and this can be explained, at least in part, by the decrease in hormone replacement therapy use by post-menopausal women. Chemoprevention has the potential to be an approach of utmost importance to reduce cancer burden at least among high-risk populations. Tamoxifen and raloxifene are both indicated for the prevention of breast cancer in women at high risk for the development of the disease, although raloxifene may have a more favorable adverse-effect profile, causing fewer uterine cancers and thromboembolic events. Aromatase inhibitors will most probably become an additional prevention treatment option in the near future, in view of the promising results observed in adjuvant trials and the interesting results of the very recently published first chemoprevention trial using an aromatase inhibitor.(2) Despite impressive results in most clinical trials performed to date, chemoprevention is still not widely used. Urgently needed are better molecular risk models to accurately identify high-risk subjects, new agents with a better risk/benefit ratio and validated biomarkers. PMID:21856081

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

    ClinicalTrials.gov

    2011-12-07

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

  18. Inflammatory breast cancer in a previously treated case of breast cancer: a diagnostic dilemma for the clinician.

    PubMed

    Ravind, Rahul; Kumar, Priyadarshini Venkatram; Prabaharan, Sasikala

    2016-01-01

    Inflammatory breast cancer (IBC) is a relatively rare and aggressive subtype, accounting for nearly 2.5% of all diagnosed breast cancers worldwide. It is usually characterised by an acute onset, rapid clinical progression, poor prognosis and micrometastasis at the time of presentation. Prompt recognition of clinical symptoms and identification of warning signs are vital in diagnosing and appropriately treating a patient with IBC. PMID:27060073

  19. Tamoxifen Action in ER-Negative Breast Cancer

    PubMed Central

    Manna, Subrata; Holz, Marina K.

    2016-01-01

    Breast cancer is a highly heterogeneous disease. Tamoxifen is a selective estrogen receptor (ER) modulator and is mainly indicated for the treatment of breast cancer in postmenopausal women and postsurgery neoadjuvant therapy in ER-positive breast cancers. Interestingly, 5–10% of the ER-negative breast cancers have also shown sensitivity to tamoxifen treatment. The involvement of molecular markers and/or signaling pathways independent of ER signaling has been implicated in tamoxifen sensitivity in the ER-negative subgroup. Studies reveal that variation in the expression of estrogen-related receptor alpha, ER subtype beta, tumor microenvironment, and epigenetics affects tamoxifen sensitivity. This review discusses the background of the research on the action of tamoxifen that may inspire future studies to explore effective therapeutic strategies for the treatment of ER-negative and triple-negative breast cancers, the latter being an aggressive disease with worse clinical outcome. PMID:26989346

  20. Breast Cancer Research at NASA

    NASA Technical Reports Server (NTRS)

    1998-01-01

    Dr. Robert Richmond extracts breast cell tissue from one of two liquid nitrogen dewars. NASA's Marshall Space Flight Center (MSFC) is sponsoring research with Bioreactors, rotating wall vessels designed to grow tissue samples in space, to understand how breast cancer works. This ground-based work studies the growth and assembly of human mammary epithelial cells (HMEC) from breast cancer susceptible tissue. Radiation can make the cells cancerous, thus allowing better comparisons of healthy vs. tunourous tissues.

  1. Breast Cancer Research at NASA

    NASA Technical Reports Server (NTRS)

    1998-01-01

    Breast tissue specimens in traditional sample dishes. NASA's Marshall Space Flight Center (MSFC) is sponsoring research with Bioreactors, rotating wall vessels designed to grow tissue samples in space, to understand how breast cancer works. This ground-based work studies the growth and assembly of human mammary epithelial cells (HMEC) from breast cancer susceptible tissue. Radiation can make the cells cancerous, thus allowing better comparisons of healthy vs. tunourous tissues.

  2. Male breast cancer.

    PubMed

    Jepson, A S; Fentiman, I S

    1998-01-01

    Male breast cancer is a rare disease, often with a late presentation and poor prognosis. The mainstay of treatment is modified radical mastectomy, with axillary node dissection to assess stage, prognosis and the need for adjuvant treatment. When matched for age, tumour size, grade and axillary nodal status, the prognosis is similar for males and females. Concerted efforts must be made to educate both the public and health professionals, in order to make earlier diagnoses and thereby improve prognosis. PMID:10622057

  3. Breast Cancer Research at NASA

    NASA Technical Reports Server (NTRS)

    1998-01-01

    High magnification view of human primary breast tumor cells after 56 days of culture in a NASA Bioreactor. The arrow points to bead surface indicating breast cancer cells (as noted by the staining of tumor cell intermediate filaments). NASA's Marshall Space Flight Center (MSFC) is sponsoring research with Bioreactors, rotating wall vessels designed to grow tissue samples in space, to understand how breast cancer works. This ground-based work studies the growth and assembly of human mammary epithelial cell (HMEC) from breast cancer susceptible tissue. Radiation can make the cells cancerous, thus allowing better comparisons of healthy vs. tunorous tissue. Credit: Dr. Jearne Becker, University of South Florida

  4. Breast cancer risk factors

    PubMed Central

    Ciszewski, Tomasz; Łopacka-Szatan, Karolina; Miotła, Paweł; Starosławska, Elżbieta

    2015-01-01

    Breast cancer is the most frequently diagnosed neoplastic disease in women around menopause often leading to a significant reduction of these women's ability to function normally in everyday life. The increased breast cancer incidence observed in epidemiological studies in a group of women actively participating in social and professional life implicates the necessity of conducting multidirectional studies in order to identify risk factors associated with the occurrence of this type of neoplasm. Taking the possibility of influencing the neoplastic transformation process in individuals as a criterion, all the risk factors initiating the process can be divided into two groups. The first group would include inherent factors such as age, sex, race, genetic makeup promoting familial occurrence of the neoplastic disease or the occurrence of benign proliferative lesions of the mammary gland. They all constitute independent parameters and do not undergo simple modification in the course of an individual's life. The second group would include extrinsic factors conditioned by lifestyle, diet or long-term medical intervention such as using oral hormonal contraceptives or hormonal replacement therapy and their influence on the neoplastic process may be modified to a certain degree. Identification of modifiable factors may contribute to development of prevention strategies decreasing breast cancer incidence. PMID:26528110

  5. Molecular Targeted Therapies of Aggressive Thyroid Cancer

    PubMed Central

    Ferrari, Silvia Martina; Fallahi, Poupak; Politti, Ugo; Materazzi, Gabriele; Baldini, Enke; Ulisse, Salvatore; Miccoli, Paolo; Antonelli, Alessandro

    2015-01-01

    Differentiated thyroid carcinomas (DTCs) that arise from follicular cells account >90% of thyroid cancer (TC) [papillary thyroid cancer (PTC) 90%, follicular thyroid cancer (FTC) 10%], while medullary thyroid cancer (MTC) accounts <5%. Complete total thyroidectomy is the treatment of choice for PTC, FTC, and MTC. Radioiodine is routinely recommended in high-risk patients and considered in intermediate risk DTC patients. DTC cancer cells, during tumor progression, may lose the iodide uptake ability, becoming resistant to radioiodine, with a significant worsening of the prognosis. The lack of specific and effective drugs for aggressive and metastatic DTC and MTC leads to additional efforts toward the development of new drugs. Several genetic alterations in different molecular pathways in TC have been shown in the past few decades, associated with TC development and progression. Rearranged during transfection (RET)/PTC gene rearrangements, RET mutations, BRAF mutations, RAS mutations, and vascular endothelial growth factor receptor 2 angiogenesis pathways are some of the known pathways determinant in the development of TC. Tyrosine kinase inhibitors (TKIs) are small organic compounds inhibiting tyrosine kinases auto-phosphorylation and activation, most of them are multikinase inhibitors. TKIs act on the aforementioned molecular pathways involved in growth, angiogenesis, local, and distant spread of TC. TKIs are emerging as new therapies of aggressive TC, including DTC, MTC, and anaplastic thyroid cancer, being capable of inducing clinical responses and stabilization of disease. Vandetanib and cabozantinib have been approved for the treatment of MTC, while sorafenib and lenvatinib for DTC refractory to radioiodine. These drugs prolong median progression-free survival, but until now no significant increase has been observed on overall survival; side effects are common. New efforts are made to find new more effective and safe compounds and to personalize the therapy in

  6. Tomosynthesis for breast cancer screening.

    PubMed

    Cole, Elodia B; Pisano, Etta D

    2016-01-01

    Breast tomosynthesis, a three-dimensional x-ray based breast imaging technology, has been available for clinical use in the United States since 2011. In this paper we review the literature on breast cancer screening with this new technology including where gaps in knowledge remain. PMID:26472036

  7. Targeting Breast Cancer Stem Cells

    PubMed Central

    Liu, Suling; Wicha, Max S.

    2010-01-01

    There is increasing evidence that many cancers, including breast cancer, contain populations of cells that display stem-cell properties. These breast cancer stem cells, by virtue of their relative resistance to radiation and cytotoxic chemotherapy, may contribute to treatment resistance and relapse. The elucidation of pathways that regulate these cells has led to the identification of potential therapeutic targets. A number of agents capable of targeting breast cancer stem cells in preclinical models are currently entering clinical trials. Assessment of the efficacy of the agents will require development of innovative clinical trial designs with appropriate biologic and clinical end points. The effective targeting of breast cancer stem cells has the potential to significantly improve outcome for women with both early-stage and advanced breast cancer. PMID:20498387

  8. Drugs Approved for Breast Cancer

    Cancer.gov

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for breast cancer. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters.

  9. Circadian clocks and breast cancer.

    PubMed

    Blakeman, Victoria; Williams, Jack L; Meng, Qing-Jun; Streuli, Charles H

    2016-01-01

    Circadian clocks respond to environmental time cues to coordinate 24-hour oscillations in almost every tissue of the body. In the breast, circadian clocks regulate the rhythmic expression of numerous genes. Disrupted expression of circadian genes can alter breast biology and may promote cancer. Here we overview circadian mechanisms, and the connection between the molecular clock and breast biology. We describe how disruption of circadian genes contributes to cancer via multiple mechanisms, and link this to increased tumour risk in women who work irregular shift patterns. Understanding the influence of circadian rhythms on breast cancer could lead to more efficacious therapies, reformed public health policy and improved patient outcome. PMID:27590298

  10. Vascular and Cognitive Assessments in Patients With Breast Cancer Undergoing Chemotherapy After Surgery

    ClinicalTrials.gov

    2015-07-27

    Cognitive/Functional Effects; Recurrent Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

  11. Understanding your breast cancer risk

    MedlinePlus

    ... what you can do to help prevent breast cancer. Risk Factors You Cannot Control Risk factors you cannot control ... risk. Race . White women are diagnosed with breast cancer more often than African American/black, ... Can Control Risk factors you can control ...

  12. Breast and Colon Cancer Family Registries

    Cancer.gov

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

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

    ClinicalTrials.gov

    2016-02-09

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

  14. How to target estrogen receptor-negative breast cancer?

    PubMed

    Rochefort, H; Glondu, M; Sahla, M E; Platet, N; Garcia, M

    2003-06-01

    Estrogen receptor (ER)-positive breast cancers generally have a better prognosis and are often responsive to anti-estrogen therapy, which is the first example of a successful therapy targeted on a specific protein, the ER. Unfortunately ER-negative breast cancers are more aggressive and unresponsive to anti-estrogens. Other targeted therapies are thus urgently needed, based on breast cancer oncogene inhibition or suppressor gene activation as far as molecular studies have demonstrated the alteration of expression, or structure of these genes in human breast cancer. Using the MDA-MB.231 human breast cancer cell line as a model of ER-negative breast cancers, we are investigating two of these approaches in our laboratory. Our first approach was to transfect the ER or various ER-deleted variants into an ER-negative cell line in an attempt to recover anti-estrogen responsiveness. The unliganded receptor, and surprisingly estradiol, were both found to inhibit tumor growth and invasiveness in vitro and in vivo. The mechanisms of these inhibitions in ER-negative cancer cells are being studied, in an attempt to target the ER sequence responsible for such inhibition in these cancer cells. Another strategy is trying to inhibit the activity or expression of an oncogene specifically overexpressed in most breast cancers. This approach was recently shown by others to be efficient in breast cancer therapy with HER2-Neu oncogene amplification using Herceptin. Without excluding other molecular putative targets, we have focused our research on cathepsin D as a potential target, since it is often overexpressed in aggressive human breast cancers, including ER-negative tumors, and rarely associated with HER2-Neu amplification. Our first results obtained in vitro on cell lines and in vivo in tumor xenografts in nude mice, illustrate that the mode of action of cathepsin D in breast cancer is useful to guide the development of these therapies. In the past 20 years we have learned that the

  15. Green Tea and Breast Cancer

    PubMed Central

    Wu, Anna H; Butler, Lesley M

    2014-01-01

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

  16. CCN6: a modulator of breast cancer progression.

    PubMed

    Leask, Andrew

    2016-06-01

    The expression of the CCN family of matricellular proteins is highly dysregulated in connective tissue pathologies such as fibrosis and highly metastatic cancers. Strategies targeting members of this family, especially CCN2, are under development as novel therapeutic approaches to highly metastatic cancers such as pancreatic cancer. In prior reports, the Kleer laboratory and colleagues have linked reduced expression of CCN6 (WISP3) with aggressive breast cancers. Loss of CCN6 was associated with elevated Akt phosphorylation and TAK1 activation. In a recent report, the same group reports that, by modulating Notch signaling, CCN6 can promote the maintenance of an epithelial phenotype and also reduce cancer cell migration and invasion, tumor initiation, and metastasis (Oncotarget in press DOI: 10.18632/oncotarget.7734 ). These results are consistent with the hypothesis that addition of CCN6 peptides may represent a novel, viable therapeutic approach to blocking aggressive breast cancers. PMID:27086280

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

    ClinicalTrials.gov

    2016-09-15

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

  18. Curing Metastatic Breast Cancer.

    PubMed

    Sledge, George W

    2016-01-01

    Metastatic breast cancer is generally considered incurable, and this colors doctor-patient interactions for patients with metastatic disease. Although true for most patients, there appear to be important exceptions, instances where long-term disease-free survival occurs. Although these instances are few in number, they suggest the possibility of cure. How will we move toward cure for a much larger population of patients with metastatic disease? This article outlines a potential research agenda that might move us toward that distant goal. PMID:26759458

  19. Optimal breast cancer pathology manifesto.

    PubMed

    Tot, T; Viale, G; Rutgers, E; Bergsten-Nordström, E; Costa, A

    2015-11-01

    This manifesto was prepared by a European Breast Cancer (EBC) Council working group and launched at the European Breast Cancer Conference in Glasgow on 20 March 2014. It sets out optimal technical and organisational requirements for a breast cancer pathology service, in the light of concerns about variability and lack of patient-centred focus. It is not a guideline about how pathology services should be performed. It is a call for all in the cancer community--pathologists, oncologists, patient advocates, health administrators and policymakers--to check that services are available that serve the needs of patients in a high quality, timely way. PMID:26283037

  20. Treating Male Breast Cancer by Stage

    MedlinePlus

    ... men treated? Surgery for breast cancer in men Radiation therapy for breast cancer in men Chemotherapy for breast cancer in men ... these may be used after surgery and/or radiation therapy. Regional recurrence: When breast cancer comes back in nearby lymph nodes (such as ...

  1. HER-2 Positive Breast Cancer - a Mini-Review.

    PubMed

    Asif, Hafiz Muhammad; Sultana, Sabira; Ahmed, Saeed; Akhtar, Naheed; Tariq, Muhammad

    2016-01-01

    Breast cancer is one of among all cancers with increased incidence, high mortality rate, and high economic and social costs. The the most common type of cancer among females worldwide, breast cancer is actually the uncontrolled proliferation of cells which attain malignancy. Recently it has shown that breast cancer contributes 11% among all types of cancer diagnosed globally on an annual basis and it is one of the leading causes of death among women. The human epidermal growth factor receptor 2 (HER-2) is a receptor tyrosine-protein kinase erbB-2 normally involved in the proliferation and division of breast cells. In some abnormal cases the HER2 gene does not work correctly and makes too many copies of itself. HER2-positive (HER2+) breast cancers constitute an aggressive type of breast cancer and tend to grow faster and are more likely to spread. However, therapies that specifically target HER2, such as Herceptin® (traztuzumab), are very effective. HER2 targeted therapies, has significantly improved the therapeutic outcome for patients with HER2 positive breast cancer. PMID:27221828

  2. Could Certain Fatty Foods Be Linked to Aggressive Prostate Cancer?

    MedlinePlus

    ... Could Certain Fatty Foods Be Linked to Aggressive Prostate Cancer? Study also suggests that cholesterol-lowering drugs may ... meats and cheese -- may affect how quickly their prostate cancer progresses, a new study suggests. "We show that ...

  3. African American Women’s Perspectives on Breast Cancer: Implications for Communicating Risk of Basal-like Breast Cancer

    PubMed Central

    Allicock, Marlyn; Graves, Neasha; Gray, Kathleen; Troester, Melissa A.

    2013-01-01

    African American women suffer a higher burden of basal-like breast cancer, an aggressive subtype that has no targeted therapy. While epidemiologic research has identified key prevention strategies, little is known about how best to communicate risk to this population. This study explored women’s knowledge, beliefs, and attitudes about breast cancer to learn about risk perceptions. Six focus groups with 57 women (ages 18–49) women were conducted in North Carolina. Findings revealed that age, race (especially perceptions of cancer as a “White disease”), and lack of family history of breast cancer contributed to women’s perceptions of low breastcancer susceptibility. Perceptions of low risk were also attributed to conflicting risk information from family, media, and health providers. Women had little knowledge about breast cancer subtypes, but emphasized that health communications should be personally relevant, culturally appropriate, and convenient. These study findings will assist in developing health communication tools that encourage prevention. PMID:23728042

  4. Aluminium, antiperspirants and breast cancer.

    PubMed

    Darbre, P D

    2005-09-01

    Aluminium salts are used as the active antiperspirant agent in underarm cosmetics, but the effects of widespread, long term and increasing use remain unknown, especially in relation to the breast, which is a local area of application. Clinical studies showing a disproportionately high incidence of breast cancer in the upper outer quadrant of the breast together with reports of genomic instability in outer quadrants of the breast provide supporting evidence for a role for locally applied cosmetic chemicals in the development of breast cancer. Aluminium is known to have a genotoxic profile, capable of causing both DNA alterations and epigenetic effects, and this would be consistent with a potential role in breast cancer if such effects occurred in breast cells. Oestrogen is a well established influence in breast cancer and its action, dependent on intracellular receptors which function as ligand-activated zinc finger transcription factors, suggests one possible point of interference from aluminium. Results reported here demonstrate that aluminium in the form of aluminium chloride or aluminium chlorhydrate can interfere with the function of oestrogen receptors of MCF7 human breast cancer cells both in terms of ligand binding and in terms of oestrogen-regulated reporter gene expression. This adds aluminium to the increasing list of metals capable of interfering with oestrogen action and termed metalloestrogens. Further studies are now needed to identify the molecular basis of this action, the longer term effects of aluminium exposure and whether aluminium can cause aberrations to other signalling pathways in breast cells. Given the wide exposure of the human population to antiperspirants, it will be important to establish dermal absorption in the local area of the breast and whether long term low level absorption could play a role in the increasing incidence of breast cancer. PMID:16045991

  5. Breast Cancer Research at NASA

    NASA Technical Reports Server (NTRS)

    1998-01-01

    Time-lapse exposure depicts Bioreactor rotation. NASA's Marshall Space Flight Center (MSFC) is sponsoring research with Bioreactors, rotating wall vessels designed to grow tissue samples in space, to understand how breast cancer works. This ground-based work studies the growth and assembly of human mammary epithelial cells (HMEC) from breast cancer susceptible tissue. Radiation can make the cells cancerous, thus allowing better comparisons of healthy vs. tunourous tissues.

  6. Carboplatin and Combination Chemotherapy With or Without Veliparib in Treating Patients With Stage IIB-IIIC Breast Cancer

    ClinicalTrials.gov

    2015-10-12

    Estrogen Receptor-negative Breast Cancer; HER2-negative Breast Cancer; Progesterone Receptor-negative Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Triple-negative Breast Cancer

  7. Addition of Carboplatin to Neoadjuvant Therapy for Triple-negative and HER2-positive Early Breast Cancer

    ClinicalTrials.gov

    2016-02-12

    Tubular Breast Cancer Stage II; Mucinous Breast Cancer Stage II; Breast Cancer Female NOS; Invasive Ductal Breast Cancer; Tubular Breast Cancer Stage III; HER-2 Positive Breast Cancer; Inflammatory Breast Cancer Stage IV; Inflammatory Breast Cancer

  8. Male breast cancer.

    PubMed

    Ottini, Laura; Palli, Domenico; Rizzo, Sergio; Federico, Mario; Bazan, Viviana; Russo, Antonio

    2010-02-01

    Male breast cancer (MaleBC) is a rare disease, accounting for <1% of all male tumors. During the last few years, there has been an increase in the incidence of this disease, along with the increase in female breast cancer (FBC). Little is known about the etiology of MaleBC: hormonal, environmental and genetic factors have been reported to be involved in its pathogenesis. Major risk factors include clinical disorders carrying hormonal imbalances, radiation exposure and, in particular, a positive family history (FH) for BC, the latter suggestive of genetic susceptibility. Rare mutations in high-penetrance genes (BRCA1 and BRCA2) confer a high risk of BC development; low-penetrance gene mutations (i.e. CHEK-2) are more common but involve a lower risk increase. About 90% of all male breast tumors have proved to be invasive ductal carcinomas, expressing high levels of hormone receptors with evident therapeutic returns. The most common clinical sign of BC onset in men is a painless palpable retroareolar lump, which should be evaluated by means of mammography, ultrasonography and core biopsy or fine needle aspiration (FNA). To date, there are no published data from prospective randomized trials supporting a specific therapeutic approach in MaleBC. Tumor size together with the number of axillary nodes involved are the main prognostic factors and should guide the treatment choice. Locoregional approaches include surgery and radiotherapy (RT), depending upon the initial clinical presentation. When systemic treatment (adjuvant, neoadjuvant and metastatic) is delivered, the choice between hormonal and or chemotherapy (CT) should depend upon the clinical and biological features, according to the FBC management guidelines. However great caution is required because of high rates of age-related comorbidities. PMID:19427229

  9. Neo-adjuvant Therapy With Anastrozole Plus Pazopanib in Stage II and III ER+ Breast Cancer

    ClinicalTrials.gov

    2016-05-24

    Estrogen Receptor-positive Breast Cancer; Human Epidermal Growth Factor 2 Negative Carcinoma of Breast; Male Breast Cancer; Recurrent Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer

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

    ClinicalTrials.gov

    2016-07-12

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

  11. Polyunsaturated fatty acid content is increased in the milk of women with pregnancy associated breast cancer

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: Pregnancy associated breast cancer (PABC) is aggressive and difficult to diagnose. High intake of most types of dietary fat is thought to increase breast cancer risk, however results in humans supporting this premise remain equivocal. Fatty acid (FA) concentrations in the body comprise b...

  12. Breast Cancer Research at NASA

    NASA Technical Reports Server (NTRS)

    1998-01-01

    Human primary breast tumor cells after 56 days of culture in a NASA Bioreactor. A cross-section of a construct, grown from surgical specimens of brease cancer, stained for microscopic examination, reveals areas of tumor cells dispersed throughout the non-epithelial cell background. The arrow denotes the foci of breast cancer cells. NASA's Marshall Space Flight Center (MSFC) is sponsoring research with Bioreactors, rotating wall vessels designed to grow tissue samples in space, to understand how breast cancer works. This ground-based work studies the growth and assembly of human mammary epithelial cell (HMEC) from breast cancer susceptible tissue. Radiation can make the cells cancerous, thus allowing better comparisons of healthy vs. tunorous tissue. Credit: Dr. Jearne Becker, University of South Florida

  13. Managing breast cancer in younger women: challenges and solutions

    PubMed Central

    Ademuyiwa, Foluso O; Cyr, Amy; Ivanovich, Jennifer; Thomas, Maria A

    2016-01-01

    Breast cancer in young women is relatively rare compared to breast cancer occurring in older women. Younger women diagnosed with breast cancer also tend to have a more aggressive biology and consequently a poorer prognosis than older women. In addition, they face unique challenges such as diminished fertility from premature ovarian failure, extended survivorship periods and its attendant problems, and the psychosocial impact of diagnosis, while still raising families. It is therefore imperative to recognize the unique issues that younger women face, and plan management in a multidisciplinary fashion to optimize clinical outcomes. This paper discusses the challenges of breast cancer management for young women, as well as specific issues to consider in diagnosis, treatment, and follow-up of such patients. PMID:26730210

  14. Understanding Lymphedema (For Cancers Other Than Breast Cancer)

    MedlinePlus

    ... My ACS » Understanding Lymphedema: For Cancers Other Than Breast Cancer Download Printable Version [PDF] » Lymphedema can be caused ... News About Cancer Expert Voices Blog Programs & Services Breast Cancer Support TLC Hair Loss & Mastectomy Products Hope Lodge® ...

  15. Breast Cancer Research at NASA

    NASA Technical Reports Server (NTRS)

    1998-01-01

    Human primary breast tumor cells after 49 days of growth in a NASA Bioreactor. Tumor cells aggregate on microcarrier beads (indicated by arrow). NASA's Marshall Space Flight Center (MSFC) is sponsoring research with Bioreactors, rotating wall vessels designed to grow tissue samples in space, to understand how breast cancer works. This ground-based work studies the growth and assembly of human mammary epithelial cell (HMEC) from breast cancer susceptible tissue. Radiation can make the cells cancerous, thus allowing better comparisons of healthy vs. tunorous tissue. Credit: Dr. Jearne Becker, University of South Florida

  16. Breast Cancer Research at NASA

    NASA Technical Reports Server (NTRS)

    1998-01-01

    High magnification of view of tumor cells aggregate on microcarrier beads, illustrting breast cells with intercellular boundaires on bead surface and aggregates of cells achieving 3-deminstional growth outward from bead after 56 days of culture in a NASA Bioreactor. NASA's Marshall Space Flight Center (MSFC) is sponsoring research with Bioreactors, rotating wall vessels designed to grow tissue samples in space, to understand how breast cancer works. This ground-based work studies the growth and assembly of human mammary epithelial cell (HMEC) from breast cancer susceptible tissue. Radiation can make the cells cancerous, thus allowing better comparisons of healthy vs. tunorous tissue. Credit: Dr. Jearne Becker, University of South Florida.

  17. Breast Cancer Chemotherapy and Your Heart

    MedlinePlus

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

  18. Southeastern Cancer Study Group: breast cancer studies

    SciTech Connect

    Smalley, R.V.; Bartolucci, A.A.; Moore, M.

    1983-12-01

    During the past 10 years, the Southeastern Cancer Study Group (SECSG) has been engaged in one major adjuvant study and three major advanced disease studies for patients with adenocarcinoma of the breast. The adjuvant study is demonstrating that six months of adjuvant CMF is the therapeutic equivalent of 12 months and that post-operative irradiation is of no added therapeutic benefit. In patients with advanced disease, a low dose 5 drug combination of CMFVP induces more objective responses than single agent 5FU, but improves survival only for those patients with liver metastases when compared to the sequential use of the same 5 single agents. The three drug combination, CAF, utilizing doxorubicin, induces more objective responses than low dose CMFVP, but it does not improve overall survival. The addition of a phase active combination, CAMELEON, (i.e., sequentially alternating therapy) of CAF has not improved the duration of disease control and survival for patients with liver metastases, lymphangitic and nodular lung metastases compared to CAF. Aggressive combination chemotherapeutic approaches to patients with advanced disease provide better and longer disease and tumor control but only marginal improvements in overall survival. Adding additional agents to a maximally tolerable regimen has not improved the therapeutic outcome.

  19. Current status of hormone therapy in patients with hormone receptor positive (HR+) advanced breast cancer.

    PubMed

    Dalmau, Elsa; Armengol-Alonso, Alejandra; Muñoz, Montserrat; Seguí-Palmer, Miguel Ángel

    2014-12-01

    The natural history of HR+ breast cancer tends to be different from hormone receptor-negative disease in terms of time to recurrence, site of recurrence and overall aggressiveness of the disease. The developmental strategies of hormone therapy for the treatment of breast cancer have led to the classes of selective estrogen receptor modulators, selective estrogen receptor downregulators, and aromatase inhibitors. These therapeutic options have improved breast cancer outcomes in the metastatic setting, thereby delaying the need for chemotherapy. However, a subset of hormone receptor-positive breast cancers do not benefit from endocrine therapy (intrinsic resistance), and all HR+ metastatic breast cancers ultimately develop resistance to hormonal therapies (acquired resistance). Considering the multiple pathways involved in the HR network, targeting other components of pathologically activated intracellular signaling in breast cancer may prove to be a new direction in clinical research. This review focuses on current and emerging treatments for HR+ metastatic breast cancer. PMID:25311296

  20. Understanding your breast cancer risk

    MedlinePlus

    ... the chance that you could get cancer. Some risk factors you can control, such as drinking alcohol. Others, such as family ... Risk factors you cannot control includes: Age . Your risk for breast cancer increases as you age. Most cancers are found in ...

  1. Great expectations: historical perspectives on genetic breast cancer testing.

    PubMed Central

    Lerner, B H

    1999-01-01

    Women who test positive for a genetic breast cancer marker may have more than a 50% chance of developing the disease. Although past screening technologies have sought to identify actual breast cancers, as opposed to predisposition, the history of screening may help predict the societal response to genetic testing. For decades, educational messages have encouraged women to find breast cancers as early as possible. Such messages have fostered the popular assumption that immediately discovered and treated breast cancers are necessarily more curable. Research, however, has shown that screening improves the prognosis of some--but not all--breast cancers, and also that it may lead to unnecessary interventions. The dichotomy between the advertised value of early detection and its actual utility has caused particular controversy in the United States, where the cultural climate emphasizes the importance of obtaining all possible medical information and acting on it. Early detection has probably helped to lower overall breast cancer mortality. But it has proven hard to praise aggressive screening without exaggerating its merits. Women considering genetic breast cancer testing should weight the benefits and limitations of early knowledge. Images FIGURE 1 PMID:10358693

  2. Breast cancer cell lines: friend or foe?

    PubMed Central

    Burdall, Sarah E; Hanby, Andrew M; Lansdown, Mark RJ; Speirs, Valerie

    2003-01-01

    The majority of breast cancer research is conducted using established breast cancer cell lines as in vitro models. An alternative is to use cultures established from primary breast tumours. Here, we discuss the pros and cons of using both of these models in translational breast cancer research. PMID:12631387

  3. Consumer Health Education. Breast Cancer.

    ERIC Educational Resources Information Center

    Arkansas Univ., Fayetteville, Cooperative Extension Service.

    This short booklet is designed to be used by health educators when teaching women about breast cancer and its early detection and the procedure for breast self-examination. It includes the following: (1) A one-page teaching plan consisting of objectives, subject matter, methods (including titles of films and printed materials), target audience,…

  4. Metals and Breast Cancer

    PubMed Central

    Byrne, Celia; Divekar, Shailaja D.; Storchan, Geoffrey B.; Parodi, Daniela A.; Martin, Mary Beth

    2014-01-01

    Metalloestrogens are metals that activate the estrogen receptor in the absence of estradiol. The metalloestrogens fall into two subclasses: metal/metalloid anions and bivalent cationic metals. The metal/metalloid anions include compounds such as arsenite, nitrite, selenite, and vanadate while the bivalent cations include metals such as cadmium, calcium, cobalt, copper, nickel, chromium, lead, mercury, and tin. The best studied metalloestrogen is cadmium. It is a heavy metal and a prevalent environmental contaminant with no known physiological function. This review addresses our current understanding of the mechanism by which cadmium and the bivalent cationic metals activate estrogen receptor-α. The review also summarizes the in vitro and in vivo evidence that cadmium functions as an estrogen and the potential role of cadmium in breast cancer. PMID:23338949

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

    PubMed

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

    2015-12-15

    The survival of breast cancer patients is largely influenced by tumor characteristics, such as TNM stage, tumor grade and hormone receptor status. However, there is growing evidence that inherited genetic variation might affect the disease prognosis and response to treatment. Several lines of evidence suggest that alleles influencing breast cancer risk might also be associated with breast cancer survival. We examined the associations between 35 breast cancer susceptibility loci and the disease over-all survival (OS) in 10,255 breast cancer patients from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3) of which 1,379 died, including 754 of breast cancer. We also conducted a meta-analysis of almost 35,000 patients and 5,000 deaths, combining results from BPC3 and the Breast Cancer Association Consortium (BCAC) and performed in silico analyses of SNPs with significant associations. In BPC3, the C allele of LSP1-rs3817198 was significantly associated with improved OS (HRper-allele =0.70; 95% CI: 0.58-0.85; ptrend  = 2.84 × 10(-4) ; HRheterozygotes  = 0.71; 95% CI: 0.55-0.92; HRhomozygotes  = 0.48; 95% CI: 0.31-0.76; p2DF  = 1.45 × 10(-3) ). In silico, the C allele of LSP1-rs3817198 was predicted to increase expression of the tumor suppressor cyclin-dependent kinase inhibitor 1C (CDKN1C). In the meta-analysis, TNRC9-rs3803662 was significantly associated with increased death hazard (HRMETA =1.09; 95% CI: 1.04-1.15; ptrend  = 6.6 × 10(-4) ; HRheterozygotes  = 0.96 95% CI: 0.90-1.03; HRhomozygotes  = 1.21; 95% CI: 1.09-1.35; p2DF =1.25 × 10(-4) ). In conclusion, we show that there is little overlap between the breast cancer risk single nucleotide polymorphisms (SNPs) identified so far and the SNPs associated with breast cancer prognosis, with the possible exceptions of LSP1-rs3817198 and TNRC9-rs3803662. PMID:25611573

  6. Cholesterol and Breast Cancer Pathophysiology

    PubMed Central

    Nelson, Erik R.; Chang, Ching-yi; McDonnell, Donald P.

    2014-01-01

    Cholesterol is a risk factor for breast cancer although the mechanisms by which this occurs are not well understood. One hypothesis is that dyslipidemia results in increased cholesterol content in cell membranes thus impacting membrane fluidity and subsequent signaling. Additionally, studies demonstrate that the metabolite, 27-hydroxycholesterol (27HC), can function as an estrogen, increasing the proliferation of estrogen receptor positive breast cancer cells. This was unexpected as 27HC and other oxysterols activate the liver X receptors resulting in the reduction of intracellular cholesterol. Resolution of this paradox will require a dissection of the molecular mechanisms by which ER and LXR converge in breast cancer cells. Regardless, the observation that 27HC influences breast cancer provides rationale for strategies that target cholesterol metabolism. PMID:25458418

  7. Preventing Breast Cancer: Making Progress

    MedlinePlus

    ... medical literature, the Study of Tamoxifen and Raloxifene (STAR) trial was started in 1998. That study enrolled ... in the BCPT. Studies, such as BCPT and STAR, involve women who have not had breast cancer, ...

  8. [Maternity after breast cancer treatment].

    PubMed

    Boratyn-Nowicka, Agnieszka; Sodowski, Krzysztof; Ulman-Włodarz, Izabela

    2015-01-01

    Recent years have seen a notable increase in the number of breast cancer diagnoses among women who have not fulfilled their maternity plans before the disease. Cytotoxic drugs (chemotherapy), used in the treatment of breast cancer patients, cause varying degrees of damage to the ovaries. The expected favorable effect of gonadoliberin analogues on the preservation of fertility has not been confirmed in clinical trials, and these drugs are currently not recommended for therapy. It is only the development of cryobiology and assisted reproduction techniques that make it possible to preserve the reproductive potential. The safety of the mother and the baby after breast cancer treatment is a separate issue. The available data indicate that both, pregnancy and breast-feeding are safe for the mother and the baby. However, the majority of findings come from retrospective studies covering small sample size and excluding the heterogeneity of both, cancer cells and patient clinical data. PMID:25775879

  9. Palbociclib for Advanced Breast Cancer

    Cancer.gov

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

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

    ClinicalTrials.gov

    2013-05-07

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

  11. Lipofilling in breast cancer surgery

    PubMed Central

    Lohsiriwat, Visnu; Rietjens, Mario

    2013-01-01

    Recently, lipofilling is being performed either as a part of oncoplastic technique or alone by itself for correction of defects and asymmetry after oncologic breast cancer surgery. Its efficacy, safety and technical procedures are varying among institutions and individual surgeon’s experiences. We provide a literature review and view point focus on this novel technique which emphasize on the application on breast cancer reconstruction. PMID:25083450

  12. Soy Isoflavones Supplementation in Treating Women at High Risk For or With Breast Cancer

    ClinicalTrials.gov

    2016-04-06

    BRCA1 Mutation Carrier; BRCA2 Mutation Carrier; Ductal Breast Carcinoma in Situ; Lobular Breast Carcinoma in Situ; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer

  13. Targeting autophagy in breast cancer

    PubMed Central

    Maycotte, Paola; Thorburn, Andrew

    2014-01-01

    Macroautophagy (referred to as autophagy here) is an intracellular degradation pathway enhanced in response to a variety of stresses and in response to nutrient deprivation. This process provides the cell with nutrients and energy by degrading aggregated and damaged proteins as well as compromised organelles. Since autophagy has been linked to diverse diseases including cancer, it has recently become a very interesting target in breast cancer treatment. Indeed, current clinical trials are trying to use chloroquine or hydroxychloroquine, alone or in combination with other drugs to inhibit autophagy during breast cancer therapy since chemotherapy and radiation, regimens that are used to treat breast cancer, are known to induce autophagy in cancer cells. Importantly, in breast cancer, autophagy has been involved in the development of resistance to chemotherapy and to anti-estrogens. Moreover, a close relationship has recently been described between autophagy and the HER2 receptor. Here, we discuss some of the recent findings relating autophagy and cancer with a particular focus on breast cancer therapy. PMID:25114840

  14. BREAST CANCER, DERMATOFIBROMAS AND ARSENIC

    PubMed Central

    Dantzig, Paul I

    2009-01-01

    Background: Dermatofibromas are common benign tumors in women, and breast cancer is the most common malignancy in women. The aim of this study is to determine if there is any relationship between the two conditions. Materials and Methods: Five patients with dermatofibromas and 10 control patients (two groups) had their skin biopsies measured for arsenic by inductively coupled mass spectrometry. Fifty randomly selected patients with breast cancer and 50 control patients were examined for the presence of dermatofibromas. Results: The dermatofibromas were found to have an arsenic concentration of 0.171 micrograms/gram, compared with 0.06 and 0.07 micrograms/gram of the two control groups. Forty-three out of 50 patients with breast cancer had dermatofibromas and 32/50 patients with breast cancer had multiple dermatofibromas, compared to 10/50 control patients with dermatofibromas and only 1/50 with multiple dermatofibromas. Conclusions: Arsenic is important in the development of dermatofibromas and dermatofibromas represent a reservoir and important sign of chronic arsenic exposure. Dermatofibromas represent an important sign for women at risk for breast cancer, and arsenic may represent the cause of the majority of cases of breast cancer. PMID:20049264

  15. Survivorship Care Plan in Promoting Physical Activity in Breast or Colorectal Cancer Survivors in Wisconsin

    ClinicalTrials.gov

    2016-08-19

    Cancer Survivor; Healthy Subject; Stage I Colorectal Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIA Colorectal Cancer; Stage IIB Breast Cancer; Stage IIB Colorectal Cancer; Stage IIC Colorectal Cancer; Stage IIIA Breast Cancer; Stage IIIA Colorectal Cancer; Stage IIIB Breast Cancer; Stage IIIB Colorectal Cancer; Stage IIIC Breast Cancer; Stage IIIC Colorectal Cancer

  16. Inflammatory breast cancer: A decade of experience.

    PubMed

    Do Nascimento, Vinicius C; Rajan, Ruben; Redfern, Andrew; Saunders, Christobel

    2016-09-01

    Inflammatory breast cancer (IBC) is an aggressive and rare form of breast cancer. At present, there are no established diagnostic, radiological, pathological or molecular diagnostic criteria for this entity. The aim of this study was to examine the patterns of presentation, treatment and outcomes of IBC in this institution over the course of a decade. This is a retrospective observational study using data from the Royal Perth Hospital from January 2001 to December 2010. Our results identified 57 women with IBC, representing 1.9% of all new breast cancer presentations. Human Epidermal Growth Factor Receptor 2 (HER2)-positive and triple negative tumors were overrepresented (41% and 18%, respectively). Forty-four (77%) patients had early disease at diagnosis, of whom 35 underwent surgery and 16 are relapse-free. All six patients achieving complete pathological response were relapse-free in contrast to 11 (38%) with lesser responses at a median follow-up of 59 months. Median survival in 13 patients with metastatic disease at diagnosis was 21.7 months, with two patients still in remission. Clearly, this small but important group continues to offer management challenges and warrants ongoing study, including better molecular and pathological profiling of tumors to allow improved diagnostic clarity and more effective targeted therapy. PMID:26899402

  17. Survivorship in untreated breast cancer patients.

    PubMed

    Galmarini, Carlos M; Tredan, Olivier; Galmarini, Felipe C

    2015-02-01

    In any disease, the knowledge of the natural history of untreated cases provides a real background against which the real advantages of a new treatment itself are judged. Fortunately, in the present days, there are scant data on outcomes in patients with untreated breast cancer. In an attempt to provide this background against which the virtues of current curative and palliative treatments can be more accurately assessed, we have reviewed the literature regarding published untreated breast cancer series. Taking into consideration all the difficulties of analyzing reports written on the last half of the nineteenth century or on the first half of the twentieth century, in most reports, patients survived almost 3-4 years without any type of treatment. Worth mentioning, approximately 5-10 % of untreated patients lived longer than 10 years. Thus, the spectrum of clinical aggressiveness of untreated breast cancer varies between virulence and chronic disease. These facts should be taken into account when considering the value of current treatments for early-stage disease. PMID:25588926

  18. Genomic profiling of breast cancer.

    PubMed

    Pandey, Anjita; Singh, Alok Kumar; Maurya, Sanjeev Kumar; Rai, Rajani; Tewari, Mallika; Kumar, Mohan; Shukla, Hari S

    2009-05-01

    Genome study provides significant changes in the advancement of molecular diagnosis and treatment in Breast cancer. Several recent critical advances and high-throughput techniques identified the genomic trouble and dramatically accelerated the pace of research in preventing and curing this malignancy. Tumor-suppressor genes, proto-oncogenes, DNA-repair genes, carcinogen-metabolism genes are critically involved in progression of breast cancer. We reviewed imperative finding in breast genetics, ongoing work to segregate further susceptible genes, and preliminary studies on molecular profiling. PMID:19235775

  19. Breast cancer-specific mortality in small-sized tumor with node-positive breast cancer: a nation-wide study in Korean breast cancer society.

    PubMed

    Ryu, Jai Min; Lee, Hyouk Jin; Yoon, Tae In; Lee, Eun Sook; Lee, Soo Jung; Jung, Jin Hyang; Chae, Byung Joo; Nam, Seok Jin; Lee, Jeong Eon; Lee, Se Kyung; Bae, Soo Youn; Yu, Jonghan; Kim, Seok Won

    2016-10-01

    Tumor size and number of lymph node (LN) metastases are well known as the most important prognostic factors of breast cancer. We hypothesized that very small breast cancers with LN metastasis represent a progressive biologic behavior and evaluated tumor size stratified by LN metastasis. Data between 1990 and 2010 were obtained retrospectively from the Korean Breast Cancer Society Registry with inclusion criteria of female, non-metastatic, unilateral, and T1/2 breast cancer. We collected the following variables: age at surgery, tumor size, number of LN metastases, nuclear grade (NG), lymphovascular invasion (LVI), estrogen receptor status, progesterone receptor status, and epidermal growth factor receptor-2 status. Patient characteristics were compared by means of independent t-tests for continuous variables and the Chi-square or Fisher's exact test for categorical variables. Kaplan-Meier curves, with corresponding results of log-rank tests, were constructed for breast cancer-specific survival (BCSS). Five- and eight-year breast cancer-specific mortality (BCSM) was obtained in groups of 300 patients, followed by smoothing according to the confidence interval using the lowess method. We identified 39,826 breast cancer patients who met the inclusion criteria. Among them, 1433 (3.6 %) patients died due to breast cancer. The median follow-up duration was 63.4 (3-255) months. In the multivariate analysis, age at surgery, NG, LVI, subtype, and tumor size-nodal interactions were independently associated with BCSM. The N1 group had lower BCSS for T1a than T1b. The N2+ group also had lower BCSS for T1b than T1c or T2. In the N1 group of tumors smaller than 10 mm, 5- and 8-year BCSM decreased with larger tumor size. Patients with very small tumors with LN metastasis have decreased BCSM according to increase tumor size. Small tumors with LN metastasis could have aggressive biological behavior. PMID:27590199

  20. ZEB1 turns into a transcriptional activator by interacting with YAP1 in aggressive cancer types.

    PubMed

    Lehmann, Waltraut; Mossmann, Dirk; Kleemann, Julia; Mock, Kerstin; Meisinger, Chris; Brummer, Tilman; Herr, Ricarda; Brabletz, Simone; Stemmler, Marc P; Brabletz, Thomas

    2016-01-01

    Early dissemination, metastasis and therapy resistance are central hallmarks of aggressive cancer types and the leading cause of cancer-associated deaths. The EMT-inducing transcriptional repressor ZEB1 is a crucial stimulator of these processes, particularly by coupling the activation of cellular motility with stemness and survival properties. ZEB1 expression is associated with aggressive behaviour in many tumour types, but the potent effects cannot be solely explained by its proven function as a transcriptional repressor of epithelial genes. Here we describe a direct interaction of ZEB1 with the Hippo pathway effector YAP, but notably not with its paralogue TAZ. In consequence, ZEB1 switches its function to a transcriptional co-activator of a 'common ZEB1/YAP target gene set', thereby linking two pathways with similar cancer promoting effects. This gene set is a predictor of poor survival, therapy resistance and increased metastatic risk in breast cancer, indicating the clinical relevance of our findings. PMID:26876920

  1. ZEB1 turns into a transcriptional activator by interacting with YAP1 in aggressive cancer types

    PubMed Central

    Lehmann, Waltraut; Mossmann, Dirk; Kleemann, Julia; Mock, Kerstin; Meisinger, Chris; Brummer, Tilman; Herr, Ricarda; Brabletz, Simone; Stemmler, Marc P.; Brabletz, Thomas

    2016-01-01

    Early dissemination, metastasis and therapy resistance are central hallmarks of aggressive cancer types and the leading cause of cancer-associated deaths. The EMT-inducing transcriptional repressor ZEB1 is a crucial stimulator of these processes, particularly by coupling the activation of cellular motility with stemness and survival properties. ZEB1 expression is associated with aggressive behaviour in many tumour types, but the potent effects cannot be solely explained by its proven function as a transcriptional repressor of epithelial genes. Here we describe a direct interaction of ZEB1 with the Hippo pathway effector YAP, but notably not with its paralogue TAZ. In consequence, ZEB1 switches its function to a transcriptional co-activator of a ‘common ZEB1/YAP target gene set', thereby linking two pathways with similar cancer promoting effects. This gene set is a predictor of poor survival, therapy resistance and increased metastatic risk in breast cancer, indicating the clinical relevance of our findings. PMID:26876920

  2. Inflammatory Breast Cancer

    MedlinePlus

    ... Partners & Collaborators Spotlight on Scientists Research Areas Cancer Biology Cancer Genomics Causes of Cancer Diagnosis Prevention Screening & ... Collaborators Spotlight on Scientists NCI Research Areas Cancer Biology Cancer Genomics Causes of Cancer Diagnosis Prevention Screening & ...

  3. Recent advances in cancer stem/progenitor cell research: therapeutic implications for overcoming resistance to the most aggressive cancers.

    PubMed

    Mimeault, M; Hauke, R; Mehta, P P; Batra, S K

    2007-01-01

    Overcoming intrinsic and acquired resistance of cancer stem/progenitor cells to current clinical treatments represents a major challenge in treating and curing the most aggressive and metastatic cancers. This review summarizes recent advances in our understanding of the cellular origin and molecular mechanisms at the basis of cancer initiation and progression as well as the heterogeneity of cancers arising from the malignant transformation of adult stem/progenitor cells. We describe the critical functions provided by several growth factor cascades, including epidermal growth factor receptor (EGFR), platelet-derived growth factor receptor (PDGFR), stem cell factor (SCF) receptor (KIT), hedgehog and Wnt/beta-catenin signalling pathways that are frequently activated in cancer progenitor cells and are involved in their sustained growth, survival, invasion and drug resistance. Of therapeutic interest, we also discuss recent progress in the development of new drug combinations to treat the highly aggressive and metastatic cancers including refractory/relapsed leukaemias, melanoma and head and neck, brain, lung, breast, ovary, prostate, pancreas and gastrointestinal cancers which remain incurable in the clinics. The emphasis is on new therapeutic strategies consisting of molecular targeting of distinct oncogenic signalling elements activated in the cancer progenitor cells and their local microenvironment during cancer progression. These new targeted therapies should improve the efficacy of current therapeutic treatments against aggressive cancers, and thereby preventing disease relapse and enhancing patient survival. PMID:17979879

  4. Environmental pollutants and breast cancer.

    PubMed Central

    Brody, Julia Green; Rudel, Ruthann A

    2003-01-01

    Breast cancer is the most common cancer in women and the leading cause of cancer death among women 35-54 years of age. Rising incidence, increased risk among migrants to higher risk regions, and poor prediction of individual risk have prompted a search for additional modifiable factors. Risk factors for breast cancer include reproductive characteristics associated with estrogen and other hormones, pharmaceutical hormones, and activities such as alcohol use and lack of exercise that affect hormone levels. As a result, investigation of hormonally active compounds in commercial products and pollution is a priority. Compounds that cause mammary tumors in animals are additional priorities. Animal models provide insight into possible mechanisms for effects of environmental pollutants on breast cancer and identify chemical exposures to target in epidemiologic studies. Although few epidemiologic studies have been conducted for chemical exposures, occupational studies show associations between breast cancer and exposure to certain organic solvents and polycyclic aromatic hydrocarbons (PAHs). Population-based studies have been limited to a few organochlorine compounds and PAHs and have been mostly negative. A variety of challenges in studies of breast cancer and the environment may have contributed to negative findings. Lack of exposure assessment tools and few hypothesis-generating toxicologic studies limit the scope of epidemiologic studies. Issues of timing with respect to latency and periods of breast vulnerability, and individual differences in susceptibility pose other challenges. Substantial work is needed in exposure assessment, toxicology, and susceptibility before we can expect a pay-off from large epidemiologic studies of breast cancer and environment. PMID:12826474

  5. Natural Products for Chemoprevention of Breast Cancer

    PubMed Central

    Ko, Eun-Yi; Moon, Aree

    2015-01-01

    Breast cancer is the primary cause of cancer death in women. Although current therapies have shown some promise against breast cancer, there is still no effective cure for the majority of patients in the advanced stages of breast cancer. Development of effective agents to slow, reduce, or reverse the incidence of breast cancer in high-risk women is necessary. Chemoprevention of breast cancer by natural products is advantageous, as these compounds have few side effects and low toxicity compared to synthetic compounds. In the present review, we summarize natural products which exert chemopreventive activities against breast cancer, such as curcumin, sauchinone, lycopene, denbinobin, genipin, capsaicin, and ursolic acid. This review examines the current knowledge about natural compounds and their mechanisms that underlie breast cancer chemopreventive activity both in vitro and in vivo. The present review may provide information on the use of these compounds for the prevention of breast cancer. PMID:26734584

  6. Targeting Aggressive Cancer Stem Cells in Glioblastoma

    PubMed Central

    Seymour, Tracy; Nowak, Anna; Kakulas, Foteini

    2015-01-01

    Glioblastoma (GBM) is the most common and fatal type of primary brain tumor. Gliosarcoma (GSM) is a rarer and more aggressive variant of GBM that has recently been considered a potentially different disease. Current clinical treatment for both GBM and GSM includes maximal surgical resection followed by post-operative radiotherapy and concomitant and adjuvant chemotherapy. Despite recent advances in treating other solid tumors, treatment for GBM and GSM still remains palliative, with a very poor prognosis and a median survival rate of 12–15 months. Treatment failure is a result of a number of causes, including resistance to radiotherapy and chemotherapy. Recent research has applied the cancer stem cells theory of carcinogenesis to these tumors, suggesting the existence of a small subpopulation of glioma stem-like cells (GSCs) within these tumors. GSCs are thought to contribute to tumor progression, treatment resistance, and tumor recapitulation post-treatment and have become the focus of novel therapy strategies. Their isolation and investigation suggest that GSCs share critical signaling pathways with normal embryonic and somatic stem cells, but with distinct alterations. Research must focus on identifying these variations as they may present novel therapeutic targets. Targeting pluripotency transcription factors, SOX2, OCT4, and Nanog homeobox, demonstrates promising therapeutic potential that if applied in isolation or together with current treatments may improve overall survival, reduce tumor relapse, and achieve a cure for these patients. PMID:26258069

  7. Researchers Find 8 Immune Genes in Aggressive Brain Cancer

    MedlinePlus

    ... news/fullstory_159031.html Researchers Find 8 Immune Genes in Aggressive Brain Cancer Discovery might eventually lead ... 25, 2016 (HealthDay News) -- Researchers have identified immune genes that may affect how long people live after ...

  8. [Immunotherapy opportunities in breast cancer].

    PubMed

    Pusztai, Lajos; Ladányi, Andrea; Székely, Borbála; Dank, Magdolna

    2016-03-01

    The prognostic value of tumor infiltrating lymphocytes in breast cancer has long been recognized by histopathologists. These observations were reaffirmed by recent immunohistochemistry and gene expression profiling studies that also revealed an association between greater chemotherapy sensitivity and extensive lymphocytic infiltration in early stage breast cancers treated with neoadjuvant chemotherapy. These results suggest that local anti-tumor immune response can at least partially control cancer growth and may mediate the antitumor effects of chemotherapy. However, until recently, there was no direct clinical evidence to demonstrate that enhancing anti-tumor immune response could lead to clinical benefit in breast cancer patients. The recent development of clinically effective immune checkpoint inhibitors made it possible to test the therapeutic impact of augmenting the local anti-tumor immune response. Two Phase I clinical trials using single agent anti-PD-1 (MK-3475, pembrolizumab) and anti-PD-L1 (MPDL3280A, atezolizumab) antibodies demonstrated close to 20% tumor response rates in heavily pretreated, metastatic, triple negative breast cancers. The most remarkable feature of the responses was their long duration. Several patients had disease control close to a year, or longer, which has not previously been seen with chemotherapy regimens in this patient population. A large number of clinical trials are currently underway with these and similar drugs in the neoadjuvant, adjuvant and metastatic settings to define the role of this new treatment modality in breast cancer. PMID:26934349

  9. Azacitidine and Entinostat in Treating Patients With Advanced Breast Cancer

    ClinicalTrials.gov

    2016-05-26

    Estrogen Receptor Negative; Estrogen Receptor Positive; HER2/Neu Negative; Male Breast Carcinoma; Progesterone Receptor Negative; Recurrent Breast Carcinoma; Stage IIIC Breast Cancer; Stage IV Breast Cancer; Triple-Negative Breast Carcinoma

  10. Breast Cancer Risk Prediction Models

    Cancer.gov

    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.

  11. [Breast cancer research in the era of precision medicine].

    PubMed

    Yang, H Y; Jiang, Y Z; Shao, Z M

    2016-06-23

    Precision medicine is an emerging medical strategy that takes into account individual molecular variations of disease to guide accurate prevention and treatment.Tumor molecular markers closely related to aggressive behavior and treatment response will be identified by integrating clinical information and multiple-omics, and will be verified in well-designed clinical trials. Breast cancer is a highly heterogeneous disease. Its treatment based on molecular subtyping has achieved initial success. However, drug resistance and tumor heterogeneity are still major challenges. This review will focus on the recent progress and future prospects of clinical research on breast cancer in the era of precision medicine. PMID:27346395

  12. Lipid biology of breast cancer

    PubMed Central

    Baumann, Jan; Sevinsky, Christopher; Conklin, Douglas S.

    2014-01-01

    Alterations in lipid metabolism have been reported in many types of cancer. Lipids have been implicated in the regulation of proliferation, differentiation, apoptosis, inflammation, autophagy, motility and membrane homeostasis. It is required that their biosynthesis is tightly regulated to ensure homeostasis and to prevent unnecessary energy expenditure. This review focuses on the emerging understanding of the role of lipids and lipogenic pathway regulation in breast cancer, including parallels drawn from the study of metabolic disease models, and suggestions on how these findings can potentially be exploited to promote gains in HER2/neu-positive breast cancer research. PMID:23562840

  13. Medical Prevention of Breast Cancer

    PubMed Central

    Stubert, Johannes; Dieterich, Max; Gerber, Bernd

    2014-01-01

    Summary Breast cancer is the most common cancer of women in Western Europe and North America. Effective strategies of medical prevention could reduce the burden of breast cancer mortality. The best evidence for a risk reduction exists for hormonal agents such as tamoxifen and raloxifene (22–72%) or aromatase inhibitors (50–65%). However, the severity of side effects and the lack of evidence for an improved survival compromise the risk/benefit balance. In this review the results of chemoprevention studies, including new treatment approaches, are summarized with critical discussion of their use in clinical practice. PMID:25759621

  14. Breast Cancer Research at NASA

    NASA Technical Reports Server (NTRS)

    1998-01-01

    Isolation of human mammary epithelial cells (HMEC) from breast cancer susceptible tissue. Isolate of long-term growth human mammary epithelial cells (HMEC) from outgrowth of duct element; cells shown soon after isolation and early in culture in a dish. NASA's Marshall Space Flight Center (MSFC) is sponsoring research with Bioreactors, rotating wall vessels designed to grow tissue samples in space, to understand how breast cancer works. This ground-based work studies the growth and assembly of human mammary epithelial cell (HMEC) from breast cancer susceptible tissue. Radiation can make the cells cancerous, thus allowing better comparisons of healthy vs. tunorous tissue. Credit: Dr. Robert Tichmond, NASA/Marshall Space Flight Center (MSFC).

  15. Breast Cancer Research at NASA

    NASA Technical Reports Server (NTRS)

    1998-01-01

    Isolation of human mammary epithelial cells (HMEC) from breast cancer susceptible tissue. Outgrowth of cells from duct element in upper right corner cultured in a standard dish; most cells spontaneously die during early cell divisions, but a few will establish long-term growth. NASA's Marshall Space Flight Center (MSFC) is sponsoring research with Bioreactors, rotating wall vessels designed to grow tissue samples in space, to understand how breast cancer works. This ground-based work studies the growth and assembly of human mammary epithelial cell (HMEC) from breast cancer susceptible tissue. Radiation can make the cells cancerous, thus allowing better comparisons of healthy vs. tunorous tissue. Credit: Dr. Robert Tichmond, NASA/Marshall Space Flight Center (MSFC).

  16. Breast Cancer Research at NASA

    NASA Technical Reports Server (NTRS)

    1998-01-01

    Isolation of human mammary epithelial cells (HMEC) from breast cancer susceptible tissue. Same long-term growth human mammary epithelial cells (HMEC), but after 3 weeks in concinuous culture. Note attempts to reform duct elements, but this time in two dimensions in a dish rather that in three demensions in tissue. NASA's Marshall Space Flight Center (MSFC) is sponsoring research with Bioreactors, rotating wall vessels designed to grow tissue samples in space, to understand how breast cancer works. This ground-based work studies the growth and assembly of human mammary epithelial cell (HMEC) from breast cancer susceptible tissue. Radiation can make the cells cancerous, thus allowing better comparisons of healthy vs. tunorous tissue. Credit: Dr. Robert Tichmond, NASA/Marshall Space Flight Center (MSFC).

  17. Breast cancer in young women: special considerations in multidisciplinary care

    PubMed Central

    Reyna, Chantal; Lee, Marie Catherine

    2014-01-01

    Breast cancer is one of the most prevalent cancers in females, and 5%–7% of breast cancer cases occur in women under 40 years of age. Breast cancer in the young has gained increased attention with an attempt to improve diagnosis and prognosis. Young patients tend to have different epidemiology, presenting with later stages and more aggressive phenotypes. Diagnostic imaging is also more difficult in this age group. Multidisciplinary care generally encompasses surgeons, medical oncologists, radiation oncologists, radiologists, and social workers. Other special considerations include reconstruction options, fertility, genetics, and psychosocial issues. These concerns enlarge the already diverse multidisciplinary team to incorporate new expertise, such as reproductive specialists and genetic counselors. This review encompasses an overview of the current multimodal treatment regimens and the unique challenges in treating this special population. Integration of diagnosis, treatment, and quality of life issues should be addressed and understood by each member in the interdisciplinary team in order to optimize outcomes. PMID:25300196

  18. Honoring Pioneers in Breast Cancer Research

    MedlinePlus

    ... Current Issue Past Issues Honoring Pioneers in Breast Cancer Research Past Issues / Spring 2007 Table of Contents For ... Distinguished Medical Service Award for their pioneering breast cancer research. Photo courtesy of Bill Branson, NIH In this ...

  19. Screening for Breast Cancer: Detection and Diagnosis

    MedlinePlus

    ... page please turn JavaScript on. Feature: Screening For Breast Cancer Detection and Diagnosis Past Issues / Summer 2014 Table ... States Preventive Services Task Force updated recommendations on breast cancer screening, suggesting that women ages 50 to 74 ...

  20. Breast Cancer Prevention and Early Detection

    MedlinePlus

    ... saved articles window. My Saved Articles » My ACS » Breast Cancer Prevention and Early Detection Download Printable Version [PDF] » ( ... the factors that may affect your risk for breast cancer, and find out what you can do to ...

  1. Antiperspirants/Deodorants and Breast Cancer

    MedlinePlus

    ... Overview–for health professionals Research Antiperspirants/Deodorants and Breast Cancer On This Page Can antiperspirants or deodorants cause breast cancer? What do scientists know about the ingredients in ...

  2. Screening for Breast Cancer: Staging and Treatment

    MedlinePlus

    ... page please turn JavaScript on. Feature: Screening For Breast Cancer Staging and Treatment Past Issues / Summer 2014 Table of Contents Staging The extent (stage) of breast cancer needs to be determined to help choose the ...

  3. Reproductive History and Breast Cancer Risk

    MedlinePlus

    ... Overview–for health professionals Research Reproductive History and Breast Cancer Risk On This Page Is there a relationship between pregnancy and breast cancer risk? Are any pregnancy-related factors associated with ...

  4. Breast Cancer: Match of Her Life

    MedlinePlus

    ... of this page please turn Javascript on. Feature: Breast Cancer The Match of Her Life Past Issues / Spring - ... Martina Navratilova stays strong in her battle against breast cancer and her work to help Americans live healthier, ...

  5. Treatment of Breast Cancer during Pregnancy

    MedlinePlus

    ... 2016 Back to top » Guide Topics What Is Breast Cancer? Causes, Risk Factors, and Prevention Early Detection, Diagnosis, and Staging Treating Breast Cancer Talking With Your Doctor After Treatment What`s New ...

  6. Why Breast Cancer Survivors Should Exercise

    MedlinePlus

    ... https://medlineplus.gov/news/fullstory_159781.html Why Breast Cancer Survivors Should Exercise Moderate physical activity can ease ... Excessive stress can lead to memory problems among breast cancer survivors, but exercise can help, according to new ...

  7. Honoring Pioneers in Breast Cancer Research

    MedlinePlus

    ... Home Current Issue Past Issues Honoring Pioneers in Breast Cancer Research Past Issues / Spring 2007 Table of Contents ... the Distinguished Medical Service Award for their pioneering breast cancer research. Photo courtesy of Bill Branson, NIH In ...

  8. Innovative Trials Produce Promising Breast Cancer Drugs

    MedlinePlus

    ... news/fullstory_159762.html Innovative Trials Produce Promising Breast Cancer Drugs Adaptive study design allows researchers to match ... provide a fighting chance for women with advanced breast cancer. The drugs, neratinib and veliparib, both appear effective ...

  9. Breast Cancer and Estrogen-Alone Update

    MedlinePlus

    ... Current Issue Past Issues Research News From NIH Breast Cancer and Estrogen-Alone Update Past Issues / Summer 2006 ... hormone therapy does not increase the risk of breast cancer in postmenopausal women, according to an updated analysis ...

  10. Breast Cancer and the Environment Research Program

    Cancer.gov

    The Breast Cancer and the Environment Research Program supports a multidisciplinary network of scientists, clinicians, and community partners to examine the effects of environmental exposures that may predispose a woman to breast cancer throughout her life.

  11. Breast Cancer Gene Might Lower Women's Fertility

    MedlinePlus

    ... nlm.nih.gov/medlineplus/news/fullstory_158409.html Breast Cancer Gene Might Lower Women's Fertility: Study The BRCA1 ... that is linked to a greater risk of breast cancer may also be tied to potential fertility problems, ...

  12. Breast Cancer Gene Might Lower Women's Fertility

    MedlinePlus

    ... page: https://medlineplus.gov/news/fullstory_158409.html Breast Cancer Gene Might Lower Women's Fertility: Study The BRCA1 ... that is linked to a greater risk of breast cancer may also be tied to potential fertility problems, ...

  13. [Prophylactic axillary radiotherapy for breast cancer].

    PubMed

    Rivera, S; Louvel, G; Rivin Del Campo, E; Boros, A; Oueslati, H; Deutsch, É

    2015-06-01

    Adjuvant radiotherapy, after breast conserving surgery or mastectomy for breast cancer, improves overall survival while decreasing the risk of recurrence. However, prophylactic postoperative radiotherapy of locoregional lymph nodes for breast cancer, particularly of the axillary region, is still controversial since the benefits and the risks due to axillary irradiation have not been well defined. To begin with, when performing conformal radiotherapy, volume definition is crucial for the analysis of the risk-benefit balance of any radiation treatment. Definition and contouring of the axillary lymph node region is discussed in this work, as per the recommendations of the European Society for Radiotherapy and Oncology (ESTRO). Axillary recurrences are rare, and the recent trend leads toward less aggressive surgery with regard to the axilla. In this literature review we present the data that lead us to avoid adjuvant axillary radiotherapy in pN0, pN0i+ and pN1mi patients even without axillary clearance and to perform it in some other situations. Finally, we propose an update about the potential toxicity of adjuvant axillary irradiation, which is essential for therapeutic decision-making based on current evidence, and to guide us in the evolution of our techniques and indications of axillary radiotherapy. PMID:26044178

  14. Multicenter Breast Cancer Collaborative Registry

    PubMed Central

    Sherman, Simon; Shats, Oleg; Fleissner, Elizabeth; Bascom, George; Yiee, Kevin; Copur, Mehmet; Crow, Kate; Rooney, James; Mateen, Zubeena; Ketcham, Marsha A.; Feng, Jianmin; Sherman, Alexander; Gleason, Michael; Kinarsky, Leo; Silva-Lopez, Edibaldo; Edney, James; Reed, Elizabeth; Berger, Ann; Cowan, Kenneth

    2011-01-01

    The Breast Cancer Collaborative Registry (BCCR) is a multicenter web-based system that efficiently collects and manages a variety of data on breast cancer (BC) patients and BC survivors. This registry is designed as a multi-tier web application that utilizes Java Servlet/JSP technology and has an Oracle 11g database as a back-end. The BCCR questionnaire has accommodated standards accepted in breast cancer research and healthcare. By harmonizing the controlled vocabulary with the NCI Thesaurus (NCIt) or Systematized Nomenclature of Medicine-Clinical Terms (SNOMED-CT), the BCCR provides a standardized approach to data collection and reporting. The BCCR has been recently certified by the National Cancer Institute’s Center for Biomedical Informatics and Information Technology (NCI CBIIT) as a cancer Biomedical Informatics Grid (caBIG®) Bronze Compatible product. The BCCR is aimed at facilitating rapid and uniform collection of critical information and biological samples to be used in developing diagnostic, prevention, treatment, and survivorship strategies against breast cancer. Currently, seven cancer institutions are participating in the BCCR that contains data on almost 900 subjects (BC patients and survivors, as well as individuals at high risk of getting BC). PMID:21918596

  15. Multicenter breast cancer collaborative registry.

    PubMed

    Sherman, Simon; Shats, Oleg; Fleissner, Elizabeth; Bascom, George; Yiee, Kevin; Copur, Mehmet; Crow, Kate; Rooney, James; Mateen, Zubeena; Ketcham, Marsha A; Feng, Jianmin; Sherman, Alexander; Gleason, Michael; Kinarsky, Leo; Silva-Lopez, Edibaldo; Edney, James; Reed, Elizabeth; Berger, Ann; Cowan, Kenneth

    2011-01-01

    The Breast Cancer Collaborative Registry (BCCR) is a multicenter web-based system that efficiently collects and manages a variety of data on breast cancer (BC) patients and BC survivors. This registry is designed as a multi-tier web application that utilizes Java Servlet/JSP technology and has an Oracle 11g database as a back-end. The BCCR questionnaire has accommodated standards accepted in breast cancer research and healthcare. By harmonizing the controlled vocabulary with the NCI Thesaurus (NCIt) or Systematized Nomenclature of Medicine-Clinical Terms (SNOMED-CT), the BCCR provides a standardized approach to data collection and reporting. The BCCR has been recently certified by the National Cancer Institute's Center for Biomedical Informatics and Information Technology (NCI CBIIT) as a cancer Biomedical Informatics Grid (caBIG(®)) Bronze Compatible product.The BCCR is aimed at facilitating rapid and uniform collection of critical information and biological samples to be used in developing diagnostic, prevention, treatment, and survivorship strategies against breast cancer. Currently, seven cancer institutions are participating in the BCCR that contains data on almost 900 subjects (BC patients and survivors, as well as individuals at high risk of getting BC). PMID:21918596

  16. Veliparib, Cisplatin, and Vinorelbine Ditartrate in Treating Patients With Recurrent and/or Metastatic Breast Cancer

    ClinicalTrials.gov

    2016-03-01

    Estrogen Receptor-negative Breast Cancer; HER2-negative Breast Cancer; Hereditary Breast/Ovarian Cancer - BRCA1; Hereditary Breast/Ovarian Cancer - BRCA2; Male Breast Cancer; Progesterone Receptor-negative Breast Cancer; Recurrent Breast Cancer; Stage IV Breast Cancer; Triple-negative Breast Cancer

  17. Quantitative mitochondrial redox imaging of breast cancer metastatic potential

    NASA Astrophysics Data System (ADS)

    Xu, He N.; Nioka, Shoko; Glickson, Jerry D.; Chance, Britton; Li, Lin Z.

    2010-05-01

    Predicting tumor metastatic potential remains a challenge in cancer research and clinical practice. Our goal was to identify novel biomarkers for differentiating human breast tumors with different metastatic potentials by imaging the in vivo mitochondrial redox states of tumor tissues. The more metastatic (aggressive) MDA-MB-231 and less metastatic (indolent) MCF-7 human breast cancer mouse xenografts were imaged with the low-temperature redox scanner to obtain multi-slice fluorescence images of reduced nicotinamide adenine dinucleotide (NADH) and oxidized flavoproteins (Fp). The nominal concentrations of NADH and Fp in tissue were measured using reference standards and used to calculate the Fp redox ratio, Fp/(NADH+Fp). We observed significant core-rim differences, with the core being more oxidized than the rim in all aggressive tumors but not in the indolent tumors. These results are consistent with our previous observations on human melanoma mouse xenografts, indicating that mitochondrial redox imaging potentially provides sensitive markers for distinguishing aggressive from indolent breast tumor xenografts. Mitochondrial redox imaging can be clinically implemented utilizing cryogenic biopsy specimens and is useful for drug development and for clinical diagnosis of breast cancer.

  18. Increased invasiveness and aggressiveness in breast epithelia with cytoplasmic p63 expression

    PubMed Central

    Hsiao, Yi-Hsuan; Su, Yan A.; Tsai, Horng-Der; Mason, Jeffrey T.; Chou, Ming-Chih; Man, Yan-gao

    2010-01-01

    Our previous studies revealed that pregnancy associated breast cancer (PABC) had significantly reduced nuclear p63 expression in myoepithelia, while intense cytoplasmic p63 expression in associated epithelia. Our current study assessed these epithelia using immunohistochemistry with a panel of aggressiveness and invasiveness related markers and comparative genomic hybridization (array-CGH) with over 30,000 DNA probes. These epithelia showed several unique alterations, including (1) immunohistochemical and morphological resemblance to invasive cancer, (2) significant gain in copy numbers of DNA coding genes for morphogenesis, angiogenesis, and metastasis, and (3) significant loss in copy numbers of DNA coding genes for tumor suppressors, cell adhesion, and macromolecular complex assembly or intra-cellular trafficking. Detected array-CGH alterations correlated well with in vivo expression of a number of corresponding proteins tested. These findings suggest that aberrant sub-cellular localization of p63 expression in normal or hyperplastic appearing epithelial cells may significant contribute to increased invasiveness and aggressiveness of these cells. PMID:20714441

  19. Saracatinib in Treating Patients With Metastatic or Locally Advanced Breast Cancer That Cannot Be Removed By Surgery

    ClinicalTrials.gov

    2014-04-02

    Estrogen Receptor-negative Breast Cancer; Male Breast Cancer; Progesterone Receptor-negative Breast Cancer; Recurrent Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer

  20. Fulvestrant and Palbociclib in Treating Older Patients With Hormone Responsive Breast Cancer That Cannot Be Removed by Surgery

    ClinicalTrials.gov

    2016-05-20

    Estrogen Receptor and/or Progesterone Receptor Positive; HER2/Neu Negative; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

  1. Minocycline Hydrochloride in Reducing Chemotherapy Induced Depression and Anxiety in Patients With Stage I-III Breast Cancer

    ClinicalTrials.gov

    2016-03-07

    Anxiety Disorder; Depression; Recurrent Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

  2. Heavy Metal Exposure in Predicting Peripheral Neuropathy in Patients With Stage I-III Breast Cancer Undergoing Chemotherapy

    ClinicalTrials.gov

    2015-05-01

    Male Breast Cancer; Neurotoxicity; Peripheral Neuropathy; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

  3. Internet Use and Breast Cancer Survivors

    ERIC Educational Resources Information Center

    Muhamad, Mazanah; Afshari, Mojgan; Mohamed, Nor Aini

    2011-01-01

    A survey was administered to 400 breast cancer survivors at hospitals and support group meetings in Peninsular Malaysia to explore their level of Internet use and factors related to the Internet use by breast cancer survivors. Findings of this study indicated that about 22.5% of breast cancer survivors used Internet to get information about breast…

  4. Breast Cancer, Version 3.2013

    PubMed Central

    Theriault, Richard L.; Carlson, Robert W.; Allred, Craig; Anderson, Benjamin O.; Burstein, Harold J.; Edge, Stephen B.; Farrar, William B.; Forero, Andres; Giordano, Sharon Hermes; Goldstein, Lori J.; Gradishar, William J.; Hayes, Daniel F.; Hudis, Clifford A.; Isakoff, Steven J.; Ljung, Britt-Marie E.; Mankoff, David A.; Marcom, P. Kelly; Mayer, Ingrid A.; McCormick, Beryl; Pierce, Lori J.; Reed, Elizabeth C.; Schwartzberg, Lee S.; Smith, Mary Lou; Soliman, Hatem; Somlo, George; Ward, John H.; Wolff, Antonio C.; Zellars, Richard; Shead, Dorothy A.; Kumar, Rashmi

    2014-01-01

    These NCCN Guidelines Insights highlight the important updates specific to the management of HER2-positive metastatic breast cancer in the 2013 version of the NCCN Clinical Practice Guidelines in Oncology for Breast Cancer. These include new first-line and subsequent therapy options for patients with HER2-positive metastatic breast cancer. PMID:23847214

  5. Increased Expression of Serglycin in Specific Carcinomas and Aggressive Cancer Cell Lines

    PubMed Central

    Korpetinou, Angeliki; Papachristou, Dionysios J.; Lampropoulou, Angeliki; Bouris, Panagiotis; Labropoulou, Vassiliki T.; Noulas, Argyrios; Karamanos, Nikos K.; Theocharis, Achilleas D.

    2015-01-01

    In the present pilot study, we examined the presence of serglycin in lung, breast, prostate, and colon cancer and evaluated its expression in cell lines and tissues. We found that serglycin was expressed and constitutively secreted in culture medium in high levels in more aggressive cancer cells. It is worth noticing that aggressive cancer cells that harbor KRAS or EGFR mutations secreted serglycin constitutively in elevated levels. Furthermore, we detected the transcription of an alternative splice variant of serglycin lacking exon 2 in specific cell lines. In a limited number of tissue samples analyzed, serglycin was detected in normal epithelium but was also expressed in higher levels in advanced grade tumors as shown by immunohistochemistry. Serglycin staining was diffuse, granular, and mainly cytoplasmic. In some cancer cells serglycin also exhibited membrane and/or nuclear immunolocalization. Interestingly, the stromal cells of the reactive tumor stroma were positive for serglycin, suggesting an enhanced biosynthesis for this proteoglycan in activated tumor microenvironment. Our study investigated for first time the distribution of serglycin in normal epithelial and cancerous lesions in most common cancer types. The elevated levels of serglycin in aggressive cancer and stromal cells may suggest a key role for serglycin in disease progression. PMID:26581653

  6. Can We Prevent Breast Cancer?

    PubMed Central

    Saadat, Sabiha

    2008-01-01

    Breast cancer is the second most common cancer in the world and the most common cancer in females accounting to 23% of all cases. Between January 1998 and December 2004–2004, 6,882 cases were reported from all GCC states accounting to 11.8% from all cancers and 22.7% from cancers in females. An ASR/100,000 woman was 46.4 from Bahrain, 44.3 from Kuwait, 35.5 from Qatar, 19.2 from UAE, 14.2 from Oman and 12.9 from KSA. Breast cancer is the most frequent cancer in Arab women constituting 14–42% of all women cancers. Breast cancer in Arab countries presents almost 10 yrs younger than in USA and Europe. Median age at presentation is 48–52 and 50% of all cases are below the age of 50 where as only 25% of cases in industrialized nations are below the age of 50 yrs. What we need to fight this deadly disease is opening of screening centers with trained physicians equipped with ultrasound, x-ray unit, a pathology lab and most of all a system where a patient is seen urgently on referral to a secondary level care. Health education campaigns should be organized, female medical students should be encouraged to be general surgeons in a community where social customs still have value. PMID:21475500

  7. Cdx2 Polymorphism Affects the Activities of Vitamin D Receptor in Human Breast Cancer Cell Lines and Human Breast Carcinomas

    PubMed Central

    Di Benedetto, Anna; Korita, Etleva; Goeman, Frauke; Sacconi, Andrea; Biagioni, Francesca; Blandino, Giovanni; Strano, Sabrina; Muti, Paola; Mottolese, Marcella; Falvo, Elisabetta

    2015-01-01

    Vitamin D plays a role in cancer development and acts through the vitamin D receptor (VDR). It regulates the action of hormone responsive genes and is involved in cell cycle regulation, differentiation and apoptosis. VDR is a critical component of the vitamin D pathway and different common single nucleotide polymorphisms have been identified. Cdx2 VDR polymorphism can play an important role in breast cancer, modulating the activity of VDR. The objective of this study is to assess the relationship between the Cdx2 VDR polymorphism and the activities of VDR in human breast cancer cell lines and carcinomas breast patients. Cdx2 VDR polymorphism and antiproliferative effects of vitamin D treatment were investigated in a panel of estrogen receptor-positive (MCF7 and T-47D) and estrogen receptor-negative (MDA-MB-231, SUM 159PT, SK-BR-3, BT549, MDA-MB-468, HCC1143, BT20 and HCC1954) human breast cancer cell lines. Furthermore, the potential relationship among Cdx2 VDR polymorphism and a number of biomarkers used in clinical management of breast cancer was assessed in an ad hoc set of breast cancer cases. Vitamin D treatment efficacy was found to be strongly dependent on the Cdx2 VDR status in ER-negative breast cancer cell lines tested. In our series of breast cancer cases, the results indicated that patients with variant homozygote AA were associated with bio-pathological characteristics typical of more aggressive tumours, such as ER negative, HER2 positive and G3. Our results may suggest a potential effect of Cdx2 VDR polymorphism on the efficacy of vitamin D treatment in aggressive breast cancer cells (estrogen receptor negative). These results suggest that Cdx2 polymorphism may be a potential biomarker for vitamin D treatment in breast cancer, independently of the VDR receptor expression. PMID:25849303

  8. Cdx2 polymorphism affects the activities of vitamin D receptor in human breast cancer cell lines and human breast carcinomas.

    PubMed

    Pulito, Claudio; Terrenato, Irene; Di Benedetto, Anna; Korita, Etleva; Goeman, Frauke; Sacconi, Andrea; Biagioni, Francesca; Blandino, Giovanni; Strano, Sabrina; Muti, Paola; Mottolese, Marcella; Falvo, Elisabetta

    2015-01-01

    Vitamin D plays a role in cancer development and acts through the vitamin D receptor (VDR). It regulates the action of hormone responsive genes and is involved in cell cycle regulation, differentiation and apoptosis. VDR is a critical component of the vitamin D pathway and different common single nucleotide polymorphisms have been identified. Cdx2 VDR polymorphism can play an important role in breast cancer, modulating the activity of VDR. The objective of this study is to assess the relationship between the Cdx2 VDR polymorphism and the activities of VDR in human breast cancer cell lines and carcinomas breast patients. Cdx2 VDR polymorphism and antiproliferative effects of vitamin D treatment were investigated in a panel of estrogen receptor-positive (MCF7 and T-47D) and estrogen receptor-negative (MDA-MB-231, SUM 159PT, SK-BR-3, BT549, MDA-MB-468, HCC1143, BT20 and HCC1954) human breast cancer cell lines. Furthermore, the potential relationship among Cdx2 VDR polymorphism and a number of biomarkers used in clinical management of breast cancer was assessed in an ad hoc set of breast cancer cases. Vitamin D treatment efficacy was found to be strongly dependent on the Cdx2 VDR status in ER-negative breast cancer cell lines tested. In our series of breast cancer cases, the results indicated that patients with variant homozygote AA were associated with bio-pathological characteristics typical of more aggressive tumours, such as ER negative, HER2 positive and G3. Our results may suggest a potential effect of Cdx2 VDR polymorphism on the efficacy of vitamin D treatment in aggressive breast cancer cells (estrogen receptor negative). These results suggest that Cdx2 polymorphism may be a potential biomarker for vitamin D treatment in breast cancer, independently of the VDR receptor expression. PMID:25849303

  9. Breast cancer and racial disparity between Caucasian and African American women, part 1 (BRCA-1).

    PubMed

    Tariq, Khurram; Latif, Naeem; Zaiden, Robert; Jasani, Nick; Rana, Fauzia

    2013-08-01

    Breast cancer is a commonly diagnosed malignancy and the second leading cause of cancer-related death among American women today. Despite the lower incidence of breast cancer among African American women, they are more likely to die from the disease each year than their white counterparts. We present a retrospective cohort study of the tumor registry data from electronic medical records of patients diagnosed with breast cancer at the University of Florida Health, Jacksonville from 2000 to 2005. A total of 907 patients were diagnosed with breast cancer; 445 patients with invasive breast cancer had complete medical records and were selected for this review. Much like previously published research, we found that African American patients presented with a more advanced stage and aggressive subtype of breast cancer than white patients, and were less likely to have health insurance. However, we have yet to determine if universal health care insurance can lead to improved health care access, better breast cancer awareness, and an enhanced attitude toward breast cancer screenings. Such factors would ultimately lead to an earlier diagnosis and better outcomes in both African American and white patients. We plan to investigate this critical issue in a follow-up study (BRCA-2; Breast Cancer and Racial Disparity Between Caucasian and African American Women, Part 2), which will begin a few years after the complete implementation of the universal health care law enacted by President Obama in 2010. The higher frequency of aggressive tumor subtypes in African American women warrants more attention. We suggest further research to determine whether decreasing the initial age for screening or increasing the frequency of mammograms in African American women would improve breast cancer outcomes. This study underscores the importance of identifying and preventing obstacles in routine breast cancer screening, as well as increasing breast cancer awareness. PMID:24518421

  10. [Cancer in ectopic breast tissue].

    PubMed

    Røikjer, Johan; Lindmark, Ida; Knudsen, Thor

    2015-06-15

    Two different forms of ectopic breast tissue exist in human beings: supernumerary and aberrant. Both forms are usually seen alongside the milk lines, which extend from the upper limbs to the inguinal region where they give rise to mammary glands, areolas and nipples. Although ectopic- and orthotopic breast tissue are placed in different areas of the body, they still share the same ability to undergo pathological degeneration. The focus of this case report is to shed light on this unusual form of breast cancer, and raise the level of awareness in cases with lumps located in the milk lines. PMID:26101129

  11. Inhibition of heregulin expression blocks tumorigenicity and metastasis of breast cancer

    SciTech Connect

    Tsai, Miaw-Sheue; Shamon-Taylor, Lisa A.; Mehmi, Inderjit; Tang, Careen K.; Cardillo, Marina; Lupu, Ruth

    2001-12-20

    The growth factor Heregulin (HRG) is expressed in 30% of breast cancer tumors. HRG induces tumorigenicity and metastasis of breast cancer cells. Our investigation into whether blockage of HRG reduces the aggressiveness of breast cancer cells demonstrated that transfection of MDA-MB-231 with an HRG antisense cDNA suppressed proliferation, tumorigenicity, and metastasis. Blockage of the aggressive phenotype is mediated possibly through inactivation of the erbB signaling pathways and a decrease in MMP-9 activity. Our study is the first to report that HRG is a key promoter of breast cancer progression and should be deemed as a potential target in developing therapies for the treatment of breast carcinomas.

  12. Evaluate Risk/Benefit of Nab Paclitaxel in Combination With Gemcitabine and Carboplatin Compared to Gemcitabine and Carboplatin in Triple Negative Metastatic Breast Cancer (or Metastatic Triple Negative Breast Cancer)

    ClinicalTrials.gov

    2016-09-12

    Breast Tumor; Breast Cancer; Cancer of the Breast; Estrogen Receptor- Negative Breast Cancer; HER2- Negative Breast Cancer; Progesterone Receptor- Negative Breast Cancer; Recurrent Breast Cancer; Stage IV Breast Cancer; Triple-negative Breast Cancer; Triple-negative Metastatic Breast Cancer; Metastatic Breast Cancer

  13. Breast Cancer Research at NASA

    NASA Technical Reports Server (NTRS)

    1998-01-01

    NASA's Marshall Space Flight Center (MSFC) is sponsoring research with Bioreactors, rotating wall vessels designed to grow tissue samples in space, to understand how breast cancer works. This ground-based work studies the growth and assembly of human mammary epithelial cells (HMEC) from breast cancer susceptible tissue. Radiation can make the cells cancerous, thus allowing better comparisons of healthy vs. tunourous tissues. Here, two High-Aspect Ratio Vessels turn at about 12 rmp to keep breast tissue constructs suspended inside the culture media. Syringes allow scientists to pull for analysis during growth sequences. The tube in the center is a water bubbler that dehumidifies the air to prevent evaporation of the media and thus the appearance of destructive bubbles in the bioreactor.

  14. Tamoxifen for breast cancer prevention

    SciTech Connect

    Jordan, V.C.

    1995-02-01

    The case for tamoxifen to be tested as a preventive for breast cancer has merit. Animal studies demonstrate that tamoxifen prevents mammary carcinogenesis and clinical studies now confirm that adjuvant tamoxifen therapy is the only systemic treatment that will prevent contralateral breast cancer. Developing clinical studies confirm the laboratory data that tamoxifen will maintain post-menopausal bone density in the lumbar spine and the neck of the femur; two important skeletal sites for the ultimate prevention of osteoporosis. However, a most important target site-specific effect of tamoxifen is the decrease in low-density lipoprotein cholesterol levels in postmenopausal women. This positive property of tamoxifen may be responsible for the recorded decreases in hospital visits for the treatment of cardiac conditions and the significant decrease in fatal myocardial infarction for women treated with 5 years of adjuvant tamoxifen. These data provide the scientific basis to undertake randomized, placebocontrolled clinical trials to test the worth of tamoxifen to prevent breast cancer.

  15. Denosumab in breast cancer treatment.

    PubMed

    Drooger, Jan C; van der Padt, Annemieke; Sleijfer, Stefan; Jager, Agnes

    2013-10-01

    The bone is the most common site to which breast cancer metastasises. Recently, denosumab, a fully human monoclonal antibody that binds to receptor activator of nuclear factor kappa-B ligand (RANKL) has been developed as a new targeted bone therapy. In a large randomized phase III study with a head-to-head comparison of denosumab to zoledronic acid in patients with bone metastases of breast cancer, denosumab significantly delayed the time to first skeletal related event. In the adjuvant setting denosumab significantly increased bone mineral density compared to placebo in a phase III study in patients treated with aromatase inhibitors. Preclinical data suggest an effect of denosumab on tumour growth and even on carcinogenesis. This review describes the current indications for denosumab in the various settings of breast cancer treatment, with special attention for efficacy, short and long term toxicity and other relevant issues for clinical practice. Furthermore possible and necessary future research questions are proposed. PMID:23545361

  16. How Many Etiological Subtypes of Breast Cancer: Two, Three, Four, Or More?

    PubMed Central

    Rosenberg, Philip S.; Prat, Aleix; Perou, Charles M.; Sherman, Mark E.

    2014-01-01

    Breast cancer is a heterogeneous disease, divisible into a variable number of clinical subtypes. A fundamental question is how many etiological classes underlie the clinical spectrum of breast cancer? An etiological subtype reflects a grouping with a common set of causes, whereas a clinical subtype represents a grouping with similar prognosis and/or prediction. Herein, we review the evidence for breast cancer etiological heterogeneity. We then evaluate the etiological evidence with mRNA profiling data. A bimodal age distribution at diagnosis with peak frequencies near ages 50 and 70 years is a fundamental characteristic of breast cancer for important tumor features, clinical characteristics, risk factor profiles, and molecular subtypes. The bimodal peak frequencies at diagnosis divide breast cancer overall into a “mixture” of two main components in varying proportions in different cancer populations. The first breast cancer tends to arise early in life with modal age-at-diagnosis near 50 years and generally behaves aggressively. The second breast cancer occurs later in life with modal age near 70 years and usually portends a more indolent clinical course. These epidemiological and molecular data are consistent with a two-component mixture model and compatible with a hierarchal view of breast cancers arising from two main cell types of origin. Notwithstanding the potential added value of more detailed categorizations for personalized breast cancer treatment, we suggest that the development of better criteria to identify the two proposed etiologic classes would advance breast cancer research and prevention. PMID:25118203

  17. Spontaneous regression of breast cancer.

    PubMed

    Lewison, E F

    1976-11-01

    The dramatic but rare regression of a verified case of breast cancer in the absence of adequate, accepted, or conventional treatment has been observed and documented by clinicians over the course of many years. In my practice limited to diseases of the breast, over the past 25 years I have observed 12 patients with a unique and unusual clinical course valid enough to be regarded as spontaneous regression of breast cancer. These 12 patients, with clinically confirmed breast cancer, had temporary arrest or partial remission of their disease in the absence of complete or adequate treatment. In most of these cases, spontaneous regression could not be equated ultimately with permanent cure. Three of these case histories are summarized, and patient characteristics of pertinent clinical interest in the remaining case histories are presented and discussed. Despite widespread doubt and skepticism, there is ample clinical evidence to confirm the fact that spontaneous regression of breast cancer is a rare phenomenon but is real and does occur. PMID:799758

  18. Estrogen Metabolism and Breast Cancer

    PubMed Central

    Samavat, Hamed; Kurzer, Mindy S

    2015-01-01

    There is currently accumulating evidence that endogenous estrogens play a critical role in the development of breast cancer. Estrogens and their metabolites have been studied in both pre- and postmenopausal women with more consistent results shown in the latter population, in part because of large hormonal variations during the menstrual cycle and far fewer studies having been performed in premenopausal women. In this review we describe in detail estrogen metabolism and associated genetic variations, and provide a critical review of the current literature regarding the role of estrogens and their metabolites in breast cancer risk. PMID:24784887

  19. Breast cancer. Selected legal issues.

    PubMed

    Wynstra, N A

    1994-07-01

    Several legal and ethical issues may arise during the course of screening for and diagnosis and treatment of breast cancer. Among the most active legal areas are reimbursement for therapies deemed experimental by certain insurance companies, such as high dose chemotherapy/autologous bone marrow transplantation (HDCT/ABMT) and off-label drug use; these reimbursement issues are discussed. Legal issues in mammography screening and insurance coverage and legal issues relative to informed consent in breast cancer treatment also are discussed. PMID:8004625

  20. Intensity Modulated Accelerated Partial Breast Irradiation Before Surgery in Treating Older Patients With Hormone Responsive Stage 0-I Breast Cancer

    ClinicalTrials.gov

    2016-05-04

    Ductal Breast Carcinoma in Situ; Estrogen Receptor-negative Breast Cancer; Estrogen Receptor-positive Breast Cancer; Invasive Ductal Breast Carcinoma; Invasive Ductal Breast Carcinoma With Predominant Intraductal Component; Lobular Breast Carcinoma in Situ; Medullary Ductal Breast Carcinoma With Lymphocytic Infiltrate; Mucinous Ductal Breast Carcinoma; Papillary Ductal Breast Carcinoma; Progesterone Receptor-positive Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Tubular Ductal Breast Carcinoma

  1. Occupational exposure and risk of breast cancer

    PubMed Central

    FENGA, CONCETTINA

    2016-01-01

    Breast cancer is a multifactorial disease and the most commonly diagnosed cancer in women. Traditional risk factors for breast cancer include reproductive status, genetic mutations, family history and lifestyle. However, increasing evidence has identified an association between breast cancer and occupational factors, including environmental stimuli. Epidemiological and experimental studies demonstrated that ionizing and non-ionizing radiation exposure, night-shift work, pesticides, polycyclic aromatic hydrocarbons and metals are defined environmental factors for breast cancer, particularly at young ages. However, the mechanisms by which occupational factors can promote breast cancer initiation and progression remains to be elucidated. Furthermore, the evaluation of occupational factors for breast cancer, particularly in the workplace, also remains to be explained. The present review summarizes the occupational risk factors and the associated mechanisms involved in breast cancer development, in order to highlight new environmental exposures that could be correlated to breast cancer and to provide new insights for breast cancer prevention in the occupational settings. Furthermore, this review suggests that there is a requirement to include, through multidisciplinary approaches, different occupational exposure risks among those associated with breast cancer development. Finally, the design of new epigenetic biomarkers may be useful to identify the workers that are more susceptible to develop breast cancer. PMID:26998264

  2. Skeletal Manifestations of Treatment of Breast Cancer

    PubMed Central

    Choksi, Palak; Williams, Margaret; Clark, Patricia M.; Van Poznak, Catherine

    2014-01-01

    Breast cancer and osteoporosis are common diagnoses in women. Breast cancer survival has improved due to earlier detection and improved treatments. As most breast cancers are estrogen receptor positive, treatment is often aimed at altering the hormonal environment. Both pre and postmenopausal women undergoing these therapies are at risk for bone loss. The patient's health care team ought to have an awareness of the potential for breast cancer treatments to accelerate bone loss. Women with early stage breast cancer are treated with curative intent and, therefore, maintaining bone health is important and is part of the survivorship care to ensure an optimal quality of life. PMID:24132726

  3. Breast cancer epidemiology and risk factors.

    PubMed

    Broeders, M J; Verbeek, A L

    1997-09-01

    Breast cancer is the most common malignancy among women in the Western society. Over the past decades it has become apparent that breast cancer incidence rates are increasing steadily, whereas the mortality rates for breast cancer have remained relatively constant. Information through the media on this rising number of cases has increased breast health awareness but has also introduced anxiety in the female population. This combination of factors has made the need for prevention of breast cancer an urgent matter. Breast cancer does not seem to be a single disease entity. A specific etiologic factor may therefore have more influence on one form of breast cancer than another. So far though, as shown in our 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 in 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. PMID:9274126

  4. Breast cancer causes and treatment: where are we going wrong?

    PubMed Central

    Seymour, Colin B; Mothersill, Carmel

    2013-01-01

    This discussion paper seeks to provoke thoughts about cancer research in general, and why breast cancer in particular is not yet “curable”. It asks the question – are we looking at the disease in the right way? Should we regard cancer as a progressive state, which is part of aging? Should we tailor treatment to “reset” the system or slow progression rather than try using toxic and aggressive therapy to kill every cancer cell (and sometimes also the patient)? The thesis is presented that we need to revisit our fundamental beliefs about the disease and then ask why we cling to beliefs that clearly are no longer valid. The paper also questions the role of ethics boards in hampering research and discusses the concept that breast cancer is an industry with vested interests involving profiteering by preventive, diagnostic, and therapeutic players. Finally, the paper suggests some ways forward based on emerging concepts in system biology and epigenetics. PMID:24648764

  5. Breast cancer causes and treatment: where are we going wrong?

    PubMed

    Seymour, Colin B; Mothersill, Carmel

    2013-01-01

    This discussion paper seeks to provoke thoughts about cancer research in general, and why breast cancer in particular is not yet "curable". It asks the question - are we looking at the disease in the right way? Should we regard cancer as a progressive state, which is part of aging? Should we tailor treatment to "reset" the system or slow progression rather than try using toxic and aggressive therapy to kill every cancer cell (and sometimes also the patient)? The thesis is presented that we need to revisit our fundamental beliefs about the disease and then ask why we cling to beliefs that clearly are no longer valid. The paper also questions the role of ethics boards in hampering research and discusses the concept that breast cancer is an industry with vested interests involving profiteering by preventive, diagnostic, and therapeutic players. Finally, the paper suggests some ways forward based on emerging concepts in system biology and epigenetics. PMID:24648764

  6. PCNA immunostaining in breast cancer.

    PubMed

    Cummings, M C; Furnival, C M; Parsons, P G; Townsend, E

    1993-08-01

    Expression of proliferating cell nuclear antigen (PCNA) has been shown to be of prognostic value in patients with certain types of cancer. The aim of this study was to determine if the abundance of PCNA is inversely correlated with survival of patients with breast cancer. Paraffin blocks were available from 68 patients, all of whom had been followed clinically for at least 5 years. Sections from 20 patients showed no reactivity to PCNA and were excluded from the study because it was not possible to distinguish between true negatives and false negatives (those due to poor fixation of the original specimens). The PCNA index (the number of stained cancer cells as a percentage of the total number of cancer cells present) was calculated for the remaining 48 patients. Results were analysed by Wilcoxon's rank sum test (two tailed) and Pearson's correlation coefficient. There was no statistical difference between the PCNA indices of those patients dead from their disease within 5 years of diagnosis compared with those alive and without signs of breast cancer at 5 years. There was also no correlation between PCNA index and size of the cancer, involvement of axillary lymph nodes, time to recurrence or time to death. There was, however, a significant correlation between PCNA index and histological grade (P = 0.029). It appears that PCNA staining of stored paraffin sections is of little prognostic value in patients with breast cancer. PMID:8101708

  7. What Breast Cancer Survivors Need to Know about Osteoporosis

    MedlinePlus

    ... browser. Home Osteoporosis Osteoporosis and Other Conditions What Breast Cancer Survivors Need to Know About Osteoporosis Publication available ... Print-Friendly Page April 2016 The Impact of Breast Cancer Other than skin cancer, breast cancer is the ...

  8. Breast Cancer Death Rates Down 34% Since 1990

    MedlinePlus

    ... News » Filed under: Breast Cancer Report: Breast Cancer Death Rates Down 34% Since 1990 Article date: October ... report from the American Cancer Society finds that death rates from breast cancer in the United States ...

  9. Chordin-Like 1 Suppresses Bone Morphogenetic Protein 4-Induced Breast Cancer Cell Migration and Invasion.

    PubMed

    Cyr-Depauw, Chanèle; Northey, Jason J; Tabariès, Sébastien; Annis, Matthew G; Dong, Zhifeng; Cory, Sean; Hallett, Michael; Rennhack, Jonathan P; Andrechek, Eran R; Siegel, Peter M

    2016-05-15

    ShcA is an important mediator of ErbB2- and transforming growth factor β (TGF-β)-induced breast cancer cell migration, invasion, and metastasis. We show that in the context of reduced ShcA levels, the bone morphogenetic protein (BMP) antagonist chordin-like 1 (Chrdl1) is upregulated in numerous breast cancer cells following TGF-β stimulation. BMPs have emerged as important modulators of breast cancer aggressiveness, and we have investigated the ability of Chrdl1 to block BMP-induced increases in breast cancer cell migration and invasion. Breast cancer-derived conditioned medium containing elevated concentrations of endogenous Chrdl1, as well as medium containing recombinant Chrdl1, suppresses BMP4-induced signaling in multiple breast cancer cell lines. Live-cell migration assays reveal that BMP4 induces breast cancer migration, which is effectively blocked by Chrdl1. We demonstrate that BMP4 also stimulated breast cancer cell invasion and matrix degradation, in part, through enhanced metalloproteinase 2 (MMP2) and MMP9 activity that is antagonized by Chrdl1. Finally, high Chrdl1 expression was associated with better clinical outcomes in patients with breast cancer. Together, our data reveal that Chrdl1 acts as a negative regulator of malignant breast cancer phenotypes through inhibition of BMP signaling. PMID:26976638

  10. Loss of Dickkopf 3 Promotes the Tumorigenesis of Basal Breast Cancer

    PubMed Central

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

    2016-01-01

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

  11. Breast and Gynecologic Cancer | Division of Cancer Prevention

    Cancer.gov

    This group conducts and fosters the development of research on the prevention and early detection of breast cancer, cervix and human papillomavirus (HPV | Prevention and early detection of breast, cervix, endometrial and ovarian cancers and their precursors.

  12. [Breast cancer in Sub-Saharan African women: review].

    PubMed

    Ly, Madani; Antoine, Martine; André, Fabrice; Callard, Patrice; Bernaudin, Jean-François; Diallo, Dapa A

    2011-07-01

    Breast cancer is the second most frequent cancer in Sub-Saharan African women with an incidence of 15-53 per 100,000 women. Using PubMed, we reviewed all the articles published on this topic between 1989 and 2009. Breast cancer is usually diagnosed in women younger than in developed countries (mean age: 42-53 years), with later stages (III or IV, i.e. with axillary nodes and distant metastases). Reported tumors are mostly invasive ductal carcinomas with aggressive characteristics: grade III histoprognosis, absence of hormonal receptors or HER2 expression. According to the new breast cancer classification, nearly half of these tumors should be classified as triple negative. However, studies are rare and require confirmation. In conclusion, data on epidemiology and biology of breast cancer in Sub-Saharan African women are still scarce and need more extensive studies. In these countries, the pattern of breast cancer will likely change in the future, according to the evolution of lifestyle namely urbanisation. There is a great need for commitment of research and clinical resources in Sub-Saharan Africa in order to develop specific strategies. PMID:21700549

  13. Nanoparticle-based Paclitaxel vs Solvent-based Paclitaxel as Part of Neoadjuvant Chemotherapy for Early Breast Cancer (GeparSepto)

    ClinicalTrials.gov

    2016-02-09

    Tubular Breast Cancer Stage II; Mucinous Breast Cancer Stage II; Breast Cancer Female NOS; Invasive Ductal Breast Cancer; Tubular Breast Cancer Stage III; HER-2 Positive Breast Cancer; Inflammatory Breast Cancer Stage IV; Inflammatory Breast Cancer

  14. Combination Chemotherapy and Peripheral Blood Stem Cell Transplant Followed By Aldesleukin and Sargramostim in Treating Patients With Inflammatory Stage IIIB or Metastatic Stage IV Breast Cancer

    ClinicalTrials.gov

    2011-07-08

    Estrogen Receptor-negative Breast Cancer; Estrogen Receptor-positive Breast Cancer; Inflammatory Breast Cancer; Male Breast Cancer; Progesterone Receptor-negative Breast Cancer; Progesterone Receptor-positive Breast Cancer; Stage IIIB Breast Cancer; Stage IV Breast Cancer

  15. Interactive Gentle Yoga in Improving Quality of Life in Patients With Stage I-III Breast Cancer Undergoing Radiation Therapy

    ClinicalTrials.gov

    2015-02-03

    Anxiety Disorder; Depression; Ductal Breast Carcinoma in Situ; Fatigue; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

  16. Nanotechnology for breast cancer therapy.

    PubMed

    Tanaka, Takemi; Decuzzi, Paolo; Cristofanilli, Massimo; Sakamoto, Jason H; Tasciotti, Ennio; Robertson, Fredika M; Ferrari, Mauro

    2009-02-01

    Breast cancer is the field of medicine with the greatest presence of nanotechnological therapeutic agents in the clinic. A pegylated form of liposomally encapsulated doxorubicin is routinely used for treatment against metastatic cancer, and albumin nanoparticulate chaperones of paclitaxel were approved for locally recurrent and metastatic disease in 2005. These drugs have yielded substantial clinical benefit, and are steadily gathering greater beneficial impact. Clinical trials currently employing these drugs in combination with chemo and biological therapeutics exceed 150 worldwide. Despite these advancements, breast cancer morbidity and mortality is unacceptably high. Nanotechnology offers potential solutions to the historical challenge that has rendered breast cancer so difficult to contain and eradicate: the extreme biological diversity of the disease presentation in the patient population and in the evolutionary changes of any individual disease, the multiple pathways that drive disease progression, the onset of 'resistance' to established therapeutic cocktails, and the gravity of the side effects to treatment, which result from generally very poor distribution of the injected therapeutic agents in the body. A fundamental requirement for success in the development of new therapeutic strategies is that breast cancer specialists-in the clinic, the pharmaceutical and the basic biological laboratory-and nanotechnologists-engineers, physicists, chemists and mathematicians-optimize their ability to work in close collaboration. This further requires a mutual openness across cultural and language barriers, academic reward systems, and many other 'environmental' divides. This paper is respectfully submitted to the community to help foster the mutual interactions of the breast cancer world with micro- and nano-technology, and in particular to encourage the latter community to direct ever increasing attention to breast cancer, where an extraordinary beneficial impact may

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

    PubMed Central

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

    2015-01-01

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

  18. Breast density and breast cancer risk: a practical review.

    PubMed

    Wang, Amy T; Vachon, Celine M; Brandt, Kathleen R; Ghosh, Karthik

    2014-04-01

    New legislation in several states requiring breast density notification in all mammogram reports has increased awareness of breast density. Estimates indicate that up to 50% of women undergoing mammography will have high breast density; thus, with increased attention and high prevalence of increased breast density, it is crucial that primary care clinicians understand the implications of dense breasts and are able to provide appropriate counseling. This review provides an overview of breast density, specifically by defining breast density, exploring the association between breast density and breast cancer risk, both from masking and as an independent risk factor, and reviewing supplemental screening options as part of a larger framework for counseling patients with dense breasts. PMID:24684876

  19. Plasma matrix metalloproteinase 2 levels and breast cancer risk.

    PubMed

    Aroner, Sarah A; Rosner, Bernard A; Tamimi, Rulla M; Tworoger, Shelley S; Baur, Nadja; Joos, Thomas O; Hankinson, Susan E

    2015-06-01

    Matrix metalloproteinase 2 (MMP2) is an enzyme with important functions in breast cancer invasion and metastasis. However, it is unclear whether circulating MMP2 levels may predict breast cancer risk. We conducted a prospective nested case-control analysis in the Nurses' Health Study among 1136 cases who were diagnosed with invasive breast cancer between 1992 and 2004 and 1136 matched controls. All participants provided blood samples in 1989-1990, and a subset (170 cases, 170 controls) contributed an additional sample in 2000-2002. Pre-diagnostic plasma MMP2 levels were measured via immunoassay, and conditional logistic regression was performed to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs), adjusted for breast cancer risk factors. No association was observed between plasma MMP2 levels and risk of total invasive breast cancer (top vs. bottom quartile, OR=1.0; 95% CI: 0.7, 1.2; p-trend=0.89). Findings did not vary significantly by time since blood draw, body mass index, postmenopausal hormone use, or menopausal status at either blood draw or breast cancer diagnosis. MMP2 was associated with a greater risk of nodal metastases at diagnosis (top vs. bottom quartile, OR=1.5; 95% CI: 1.0, 2.2; p-heterogeneity, any vs. no lymph nodes=0.002), but no significant associations were observed with other tumor characteristics or with recurrent or fatal cancers. Plasma MMP2 levels do not appear to be predictive of total invasive breast cancer risk, although associations with aggressive disease warrant further study. PMID:25799912

  20. Plasma matrix metalloproteinase 2 levels and breast cancer risk

    PubMed Central

    Aroner, Sarah A.; Rosner, Bernard A.; Tamimi, Rulla M.; Tworoger, Shelley S.; Baur, Nadja; Joos, Thomas O.; Hankinson, Susan E.

    2015-01-01

    Matrix metalloproteinase 2 (MMP2) is an enzyme with important functions in breast cancer invasion and metastasis. However, it is unclear whether circulating MMP2 levels may predict breast cancer risk. We conducted a prospective nested case-control analysis in the Nurses’ Health Study among 1136 cases who were diagnosed with invasive breast cancer between 1992 and 2004 and 1136 matched controls. All participants provided blood samples in 1989-1990, and a subset (170 cases, 170 controls) contributed an additional sample in 2000 – 2002. Pre-diagnostic plasma MMP2 levels were measured via immunoassay, and conditional logistic regression was performed to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs), adjusted for breast cancer risk factors. No association was observed between plasma MMP2 levels and risk of total invasive breast cancer (top vs. bottom quartile, OR = 1.0; 95% CI: 0.7, 1.2; p-trend = 0.89). Findings did not vary significantly by time since blood draw, body mass index, postmenopausal hormone use, or menopausal status at either blood draw or breast cancer diagnosis. MMP2 was associated with a greater risk of nodal metastases at diagnosis (top vs. bottom quartile, OR = 1.5; 95% CI: 1.0, 2.2; p-heterogeneity, any vs. no lymph nodes = 0.002), but no significant associations were observed with other tumor characteristics or with recurrent or fatal cancers. Plasma MMP2 levels do not appear to be predictive of total invasive breast cancer risk, although associations with aggressive disease warrant further study. PMID:25799912

  1. Breast Cancer Research at NASA

    NASA Technical Reports Server (NTRS)

    1998-01-01

    Isolation of human mammary epithelial cells (HMEC) from breast cancer susceptible tissue; A: Duct element recovered from breast tissue digest. B: Outgrowth of cells from duct element in upper right corner cultured in a standard dish; most cells spontaneousely die during early cell divisions, but a few will establish long-term growth. C: Isolate of long-term frowth HMEC from outgrowth of duct element; cells shown soon after isolation and in early full-cell contact growth in culture in a dish. D: same long-term growth HMEC, but after 3 weeks in late full-cell contact growth in a continuous culture in a dish. Note attempts to reform duct elements but this in two demensions in a dish rather than in three dimensions in tissue. NASA's Marshall Space Flight Center (MSFC) is sponsoring research with Bioreactors, rotating wall vessels designed to grow tissue samples in space, to understand how breast cancer works. This ground-based work studies the growth and assembly of human mammary epithelial cell (HMEC) from breast cancer susceptible tissue. Radiation can make the cells cancerous, thus allowing better comparisons of healthy vs. tunorous tissue. Credit: Dr. Robert Richmond, NASA/Marshall Space Flight Center (MSFC).

  2. Breast Cancer Startup Challenge winners

    Cancer.gov

    Ten winners of a world-wide competition to bring emerging breast cancer research technologies to market faster were announced today by the Avon Foundation for Women, in partnership with NCI and the Center for Advancing Innovation (CAI). Avon is providing

  3. Caloric Restriction in Treating Patients With Stage 0-I Breast Cancer Undergoing Surgery and Radiation Therapy

    ClinicalTrials.gov

    2016-04-11

    Ductal Breast Carcinoma in Situ; Invasive Ductal Breast Carcinoma; Invasive Lobular Breast Carcinoma; Lobular Breast Carcinoma in Situ; Recurrent Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer

  4. Breast cancer with inguinal node recurrence.

    PubMed

    Goyal, Shikha; Puri, Tarun; Julka, Pramod K

    2015-03-01

    Surgery and irradiation for breast cancer may interfere with conventional pathways of spread, leading to bizarre patterns of dissemination through lymphatics or through hematogenous route. Lymphoscintigraphic studies may help identify nodal involvement. Other possible reasons could be occurrence of primary breast cancer in accessory breast tissue retained in the vulva following involution of milk line. We describe a case of triple negative breast cancer, who developed contralateral breast cancer during treatment. Three years later, she developed isolated inguinal nodal metastases, which responded to local radiotherapy and chemotherapy. However, the patient relapsed after 2 years and could not be salvaged thereafter. PMID:25455282

  5. What You Need to Know about Breast Cancer

    MedlinePlus

    ... Publications Reports What You Need To Know About™ Breast Cancer This booklet is about breast cancer. Learning about your cancer can help you take ... This booklet covers: Basics about breast anatomy and breast cancer Treatments for breast cancer, including taking part in ...

  6. Breast cancer in the elderly.

    PubMed

    Crivellari, Diana; Aapro, Matti; Leonard, Robert; von Minckwitz, Gunter; Brain, Etienne; Goldhirsch, Aron; Veronesi, Andrea; Muss, Hyman

    2007-05-10

    Screening and adjuvant postoperative therapies have increased survival among women with breast cancer. These tools are seldom applied in elderly patients, although the usually reported incidence of breast cancer is close to 50% in women 65 years or older, reaching 47% after 70 years in the updated Surveillance, Epidemiology, and End Results (SEER) database. Elderly breast cancer patients, even if in good medical health, were frequently excluded from adjuvant clinical trials. Women age 70 years who are fit actually have a median life expectancy of 15.5 years, ie, half of them will live much longer and will remain exposed for enough time to the potentially preventable risks of a relapse and specific death. In the last few years, a new concern about this issue has developed. Treatment now faces two major end points, as in younger women: to improve disease-free survival in the early stages, and to palliate symptoms in advanced disease. However, in both settings, the absolute benefit of treatment is critical because protecting quality of life and all its related aspects (especially functional status and independence), is crucial in older persons who have more limited life expectancy. Furthermore, the new hormonal compounds (aromatase inhibitors) and chemotherapeutic drugs (capecitabine, liposomal doxorubicin), are potentially less toxic than and equally as effective as older more established therapies. These new treatments bring new challenges including higher cost, and defining their benefit in elderly breast cancer must include an analysis of the cost/benefit ratio. These issues emphasize the urgent need to develop and support clinical trials for this older population of breast cancer patients both in the adjuvant and metastatic settings, a move that will take us from a prejudiced, age-based medicine to an evidence-based medicine. PMID:17488987

  7. Fructose as a carbon source induces an aggressive phenotype in MDA-MB-468 breast tumor cells

    PubMed Central

    MONZAVI-KARBASSI, BEHJATOLAH; HINE, R. JEAN; STANLEY, JOSEPH S.; RAMANI, VISHNU PRAKASH; CARCEL-TRULLOLS, JAIME; WHITEHEAD, TRACY L.; KELLY, THOMAS; SIEGEL, ERIC R.; ARTAUD, CECILE; SHAAF, SAEID; SAHA, RINKU; JOUSHEGHANY, FARIBA; HENRY-TILLMAN, RONDA; KIEBER-EMMONS, THOMAS

    2012-01-01

    Aberrant glycosylation is a universal feature of cancer cells, and certain glycan structures are well-known markers for tumor progression. Availability and composition of sugars in the microenvironment may affect cell glycosylation. Recent studies of human breast tumor cell lines indicate their ability to take up and utilize fructose. Here we tested the hypothesis that adding fructose to culture as a carbon source induces phenotypic changes in cultured human breast tumor cells that are associated with metastatic disease. MDA-MB-468 cells were adapted to culture media in which fructose was substituted for glucose. Changes in cell surface glycan structures, expression of genes related to glycan assembly, cytoskeleton F-actin, migration, adhesion and invasion were determined. Cells cultured in fructose expressed distinct cell-surface glycans. The addition of fructose affected sialylation and fucosylation patterns. Fructose feeding also increased binding of leukoagglutinating Phaseolus vulgaris isolectin, suggesting a possible rise in expression of branching β-1, 6 GlcNAc structures. Rhodamine-phalloidin staining revealed an altered F-actin cytoskeletal system. Fructose accelerated cellular migration and increased invasion. These data suggest that changing the carbon source of the less aggressive MDA-MB-468 cell line induced characteristics associated with more aggressive phenotypes. These data could be of fundamental importance due to the markedly increased consumption of sweeteners containing free fructose in recent years, as they suggest that the presence of fructose in nutritional micro-environment of tumor cells may negatively affect the outcome for some breast cancer patients. PMID:20664930

  8. Fructose as a carbon source induces an aggressive phenotype in MDA-MB-468 breast tumor cells.

    PubMed

    Monzavi-Karbassi, Behjatolah; Hine, R Jean; Stanley, Joseph S; Ramani, Vishnu Prakash; Carcel-Trullols, Jaime; Whitehead, Tracy L; Kelly, Thomas; Siegel, Eric R; Artaud, Cecile; Shaaf, Saeid; Saha, Rinku; Jousheghany, Fariba; Henry-Tillman, Ronda; Kieber-Emmons, Thomas

    2010-09-01

    Aberrant glycosylation is a universal feature of cancer cells, and certain glycan structures are well-known markers for tumor progression. Availability and composition of sugars in the microenvironment may affect cell glycosylation. Recent studies of human breast tumor cell lines indicate their ability to take up and utilize fructose. Here we tested the hypothesis that adding fructose to culture as a carbon source induces phenotypic changes in cultured human breast tumor cells that are associated with metastatic disease. MDA-MB-468 cells were adapted to culture media in which fructose was substituted for glucose. Changes in cell surface glycan structures, expression of genes related to glycan assembly, cytoskeleton F-actin, migration, adhesion and invasion were determined. Cells cultured in fructose expressed distinct cell-surface glycans. The addition of fructose affected sialylation and fucosylation patterns. Fructose feeding also increased binding of leukoagglutinating Phaseolus vulgaris isolectin, suggesting a possible rise in expression of branching beta-1, 6 GlcNAc structures. Rhodamine-phalloidin staining revealed an altered F-actin cytoskeletal system. Fructose accelerated cellular migration and increased invasion. These data suggest that changing the carbon source of the less aggressive MDA-MB-468 cell line induced characteristics associated with more aggressive phenotypes. These data could be of fundamental importance due to the markedly increased consumption of sweeteners containing free fructose in recent years, as they suggest that the presence of fructose in nutritional microenvironment of tumor cells may negatively affect the outcome for some breast cancer patients. PMID:20664930

  9. HSP90 Inhibitor AT13387 and Paclitaxel in Treating Patients With Advanced Triple Negative Breast Cancer

    ClinicalTrials.gov

    2016-08-15

    Estrogen Receptor Negative; HER2/Neu Negative; Progesterone Receptor Negative; Recurrent Breast Carcinoma; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer; Triple-Negative Breast Carcinoma

  10. [Vitamin D as an important steroid hormone in breast cancer].

    PubMed

    Obermannova, R; Demlová, R; Drábová, K; Melichárková, K; Greplová, K; Mrkvicová, M; Zdražilová-Dubská, L; Vyzula, R; Valík, D

    2014-01-01

    Vitamin D is the third steroid hormone playing important bio-logical roles in the development of breast cancer. Decreased plasma levels of its 25- hydroxyderivative, 25OHD, display robust associations with higher incidence of breast cancer and shorter overall survival. Although no consensus exists, most authors agree that optimal plasma levels shall be within 75- 150 nmol/ l whereas levels higher than 375 nmol/ l can be potentially toxic with higher risk of hypercalcemia. To date, no data are available on the optimal levels of vitamin D related to the risk of breast cancer development, its phenotype features and the course of the disease. Published studies mostly describe associations among higher levels of 25OHD and lower bio-logically aggressiveness of the tumor. The polymorphism of VDR gene coding for the steroid receptor for vitamin Dmay be associated with higher disease incidence and also be of negative prognostic significance in breast cancer. This review presents an overall summary of the current knowledge and publications on vitamin D and breast cancer. PMID:24945552

  11. Exploring Molecular Pathways of Triple-Negative Breast Cancer

    PubMed Central

    Wang, Yipeng; Budoff, Adam; Xu, Qiang; Lituev, Alexander; Potapova, Olga; Vansant, Gordon; Monforte, Joseph; Daraselia, Nikolai

    2011-01-01

    Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype with a high rate of proliferation and metastasis, as well as poor prognosis for advanced-stage disease. Although TNBC was previously classified together with basal-like and BRCA1/2-related breast cancers, genomic profiling now shows that there is incomplete overlap, with important distinctions associated with each subtype. The biology of TNBC is still poorly understood; therefore, to define the relative contributions of major cellular pathways in TNBC, we have studied its molecular signature based on analysis of gene expression. Comparisons were then made with normal breast tissue. Our results suggest the existence of molecular networks in TNBC, characterized by explicit alterations in the cell cycle, DNA repair, nucleotide synthesis, metabolic pathways, NF-κB signaling, inflammatory response, and angiogenesis. Moreover, we also characterized TNBC as a cancer of mixed phenotypes, suggesting that TNBC extends beyond the basal-like molecular signature and may constitute an independent subtype of breast cancer. The data provide a new insight into the biology of TNBC. PMID:22593799

  12. Breast metastasis from vaginal cancer.

    PubMed

    Chandrasekaran, Neeraja; Scharifker, Daniel; Varsegi, George; Almeida, Zoyla

    2016-01-01

    Vaginal cancer is a rare malignancy accounting for 1-2% of all pelvic neoplasms. Dissemination usually occurs through local invasion and rarely metastasises to distal locations. Metastasis of vaginal cancer to the breast is extremely infrequent and unique. A 66-year-old Asian woman presented with vaginal bleeding and was found to have a vaginal mass and a left breast mass. Pathological assessment of the biopsies revealed identical squamous cell characteristics of both masses. We describe a very rare and novel case of a distally located vaginal carcinoma with metastasis to the breast Federation of Gynecology and Obstetrics (FIGO) stage IV (FIGO IVB). Robot-assisted extrafascial total hysterectomy with local vaginal mass excision and partial mastectomy of the left breast were performed. After surgery, the patient underwent adjuvant chemotherapy followed by breast and pelvic radiotherapy, with maintained complete remission after 3 years of follow-up. This combination of findings and treatment is very distinct with a unique and favourable response. PMID:27444140

  13. Nonlinear Growth Kinetics of Breast Cancer Stem Cells: Implications for Cancer Stem Cell Targeted Therapy

    NASA Astrophysics Data System (ADS)

    Liu, Xinfeng; Johnson, Sara; Liu, Shou; Kanojia, Deepak; Yue, Wei; Singn, Udai; Wang, Qian; Wang, Qi; Nie, Qing; Chen, Hexin

    2013-08-01

    Cancer stem cells (CSCs) have been identified in primary breast cancer tissues and cell lines. The CSC population varies widely among cancerous tissues and cell lines, and is often associated with aggressive breast cancers. Despite of intensive research, how the CSC population is regulated within a tumor is still not well understood so far. In this paper, we present a mathematical model to explore the growth kinetics of CSC population both in vitro and in vivo. Our mathematical models and supporting experiments suggest that there exist non-linear growth kinetics of CSCs and negative feedback mechanisms to control the balance between the population of CSCs and that of non-stem cancer cells. The model predictions can help us explain a few long-standing questions in the field of cancer stem cell research, and can be potentially used to predict the efficicacy of anti-cancer therapy.

  14. Do We Know What Causes Breast Cancer?

    MedlinePlus

    ... cells become cancerous because of changes (mutations) in DNA. Some DNA mutations are inherited. This means the mutations are ... cancers that run in some families. But most DNA changes related to breast cancer are acquired in ...

  15. Coping with a Breast Cancer Diagnosis

    MedlinePlus

    ... cancer.org Handling treatment The goal of any breast cancer treatment is to get rid of the cancer and offer the best possible chance of survival. But even the best treatments have side effects. ...

  16. RECQL4 helicase has oncogenic potential in sporadic breast cancers.

    PubMed

    Arora, Arvind; Agarwal, Devika; Abdel-Fatah, Tarek Ma; Lu, Huiming; Croteau, Deborah L; Moseley, Paul; Aleskandarany, Mohammed A; Green, Andrew R; Ball, Graham; Rakha, Emad A; Chan, Stephen Yt; Ellis, Ian O; Wang, Lisa L; Zhao, Yongliang; Balajee, Adayabalam S; Bohr, Vilhelm A; Madhusudan, Srinivasan

    2016-03-01

    RECQL4 helicase is a molecular motor that unwinds DNA, a process essential during DNA replication and DNA repair. Germ-line mutations in RECQL4 cause type II Rothmund-Thomson syndrome (RTS), characterized by a premature ageing phenotype and cancer predisposition. RECQL4 is widely considered to be a tumour suppressor, although its role in human breast cancer is largely unknown. As the RECQL4 gene is localized to chromosome 8q24, a site frequently amplified in sporadic breast cancers, we hypothesized that it may play an oncogenic role in breast tumourigenesis. To address this, we analysed large cohorts for gene copy number changes (n = 1977), mRNA expression (n = 1977) and protein level (n = 1902). Breast cancer incidence was also explored in 58 patients with type II RTS. DNA replication dynamics and chemosensitivity was evaluated in RECQL4-depleted breast cancer cells in vitro. Amplification or gain in gene copy number (30.6%), high-level mRNA expression (51%) and high levels of protein (23%) significantly associated with aggressive tumour behaviour, including lymph node positivity, larger tumour size, HER2 overexpression, ER-negativity, triple-negative phenotypes and poor survival. RECQL4 depletion impaired the DNA replication rate and increased chemosensitivity in cultured breast cancer cells. Thus, although recognized as a 'safe guardian of the genome', our data provide compelling evidence that RECQL4 is tumour promoting in established breast cancers. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. PMID:26690729

  17. Improvement of survival and prospect of cure in patients with metastatic breast cancer.

    PubMed

    Cheng, Yee Chung; Ueno, Naoto T

    2012-07-01

    Patients with metastatic breast cancer have traditionally been considered incurable with conventional treatment. However, 5-10% of those patients survive more than 5 years, and 2-5% survive more than 10 years. Recent studies suggest that the survival of patients with metastatic breast cancer has been slowly improving. In this review, we examine the possible curative approach for a certain group of patients with metastatic breast cancer. We identify that patients most likely to benefit from such an aggressive approach are young and have good performance status, adequate body functional reserve, long disease-free interval before recurrence, oligometastatic disease, and low systemic tumor load. An aggressive multidisciplinary approach including both local treatment of macroscopic disease and systemic treatment of microscopic disease can result in prolonged disease control in certain patients with metastatic breast cancer. Whether patients with prolonged disease control are "cured" remains controversial. PMID:21567170

  18. Paclitaxel and Cyclophosphamide With or Without Trastuzumab Before Surgery in Treating Patients With Previously Untreated Stage I-III Breast Cancer

    ClinicalTrials.gov

    2012-12-12

    Estrogen Receptor-negative Breast Cancer; Estrogen Receptor-positive Breast Cancer; HER2-negative Breast Cancer; HER2-positive Breast Cancer; Progesterone Receptor-negative Breast Cancer; Progesterone Receptor-positive Breast Cancer; Stage IA Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Triple-negative Breast Cancer

  19. Reversing breast cancer stem cell into breast somatic stem cell.

    PubMed

    Wijaya, L; Agustina, D; Lizandi, A O; Kartawinata, M M; Sandra, F

    2011-02-01

    Stem cells have an important role in cell biology, allowing tissues to be renewed by freshly created cells throughout their lifetime. The specific micro-environment of stem cells is called stem cell niche; this environment influences the development of stem cells from quiescence through stages of differentiation. Recent advance researches have improved the understanding of the cellular and molecular components of the micro-environment--or niche--that regulates stem cells. We point out an important trend to the study of niche activity in breast cancers. Breast cancer has long been known to conserve a heterogeneous population of cells. While the majority of cells that make up tumors are destined to differentiate and eventually stop dividing, only minority populations of cells, termed cancer stem cell, possess extensive self renewal capability. These cancer stem cells possess characteristics of both stem cells and cancer cells. Breast cancer stem cells reversal to breast somatic stem cells offer a new therapy, that not only can stop the spread of breast cancer cells, but also can differentiate breast cancer stem cells into normal breast somatic stem cells. These can replace damaged breast tissue. Nevertheless, the complexity of realizing this therapy approach needs further research. PMID:21044008

  20. FLT PET in Measuring Treatment Response in Patients With Newly Diagnosed Estrogen Receptor-Positive, HER2-Negative Stage I-III Breast Cancer

    ClinicalTrials.gov

    2016-06-02

    Estrogen Receptor Positive; HER2/Neu Negative; Male Breast Carcinoma; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

  1. Triple negative breast cancer - our experience and review.

    PubMed

    Krishnamurthy, S; Poornima, R; Challa, Vasu Reddy; Goud, Y G Basavana

    2012-03-01

    Triple negative breast cancer (TNBC) constitutes 10-25% of patients with breast cancer. TNBC is an aggressive phenotype affecting younger age groups and has poor prognosis. We retrospectively analysed 50 triple negative breast cancer patients attending our outpatient department among 270 breast cancer patients. The incidence of TNBC was 18.5%, and most of them were premenopausal 56% (28/50) with mean age was 46.66 ± 13.87 (Range 28-72 years). Most of them had Invasive ductal cancer 94% (47/50) and were high grade (Grade 3-96%)(48/50). Five patients presented with metastatic disease (2 patients only Skeletal, 1 patient with Skeletal and Lung, 1 patient with Lung and 1 patient with Liver) and 7 patients developed recurrence (all 7 had chest wall recurrence, 3 had supraclavicular lymph node recurrence, 2 had skeletal metastases and 1 had developed brain metastases) during follow up. The mean disease free survival was 15 months (Range 3-58 months) and overall survival was 20.14 months (Range 5-70 months). Fifty six percent (28/50) of patients were premenopausal and mean age of presentation was 46.66 ± 13.87 years (Range 28-72 years). Ten percent (5/50) presented with metastatic disease and 15% (7/45) developed metastases during follow up. Five patients (10%) died during follow up. Hence, Triple negative breast cancer is aggressive, with rapid progression leading to mortality in younger patients. PMID:23449631

  2. Evolution of Imaging in Breast Cancer.

    PubMed

    Garcia, Evelyn M; Crowley, James; Hagan, Catherine; Atkinson, Lisa L

    2016-06-01

    The following topics are discussed in this article. A historical review of the evolution of breast cancer imaging from thermography through digital breast tomosynthesis, molecular breast imaging, and advanced breast magnetic resonance imaging. Discussion of multiple clinical trials, their strengths, and weaknesses. Historical perspective on the Mammography Quality Standards Act and its relationship with development and implementation of the Breast Imaging-Reporting and Data System (BI-RADS). PMID:27029017

  3. Features of triple-negative breast cancer

    PubMed Central

    Plasilova, Magdalena L.; Hayse, Brandon; Killelea, Brigid K.; Horowitz, Nina R.; Chagpar, Anees B.; Lannin, Donald R.

    2016-01-01

    Abstract The aim of this study was to determine the features of triple-negative breast cancer (TNBC) using a large national database. TNBC is known to be an aggressive subtype, but national epidemiologic data are sparse. All patients with invasive breast cancer and known molecular subtype diagnosed in 2010 to 2011 were identified from the National Cancer Data Base (NCDB). Patients with and without TNBC were compared with respect to their sociodemographic and clinicopathologic features. TNBC was present in 38,628 of 295,801 (13%) female patients compared to 185 of 3136 (6%) male patients (P < 0.001). The incidence of TNBC varied by region from 10.8% in New England to 15.8% in the east south central US (P < 0.001), as well as by race with the highest rates in African-Americans (23.7%), and lowest in Filipino patients (8.9%). The incidence of TNBC also varied by histology, accounting for 76% of metaplastic cancers, but only 2% of infiltrating lobular carcinomas. TNBCs were significantly larger than non-TNBC (mean 2.8 cm vs 2.1 cm, P < 0.001), and more TNBC were poorly differentiated compared to other subtypes (79.7% vs 25.8%, P < 0.001). On univariate analysis, TNBC was no more likely than non-TNBC to have node-positive disease (32.0% vs 31.7%, respectively, P = 0.218) but in a multivariable analysis controlling for tumor size and grade, TNBC was associated with significantly less node-positivity (OR = 0.59; 95% confidence interval [CI]: 0.57–0.60). TNBC has distinct features regarding age, gender, geographic, and racial distribution. Compared to non-TNBC, TNBC is larger and higher grade, but less likely to have lymph node metastases. PMID:27583878

  4. Fertility after breast cancer treatment.

    PubMed

    Kasum, Miro; Beketić-Orešković, Lidija; Peddi, Parvin F; Orešković, Slavko; Johnson, Rebecca H

    2014-02-01

    In many countries of the developed world, there is an increasing trend toward delay in childbearing from 30 to 40 years of age for various reasons. This is unfortunately concordant with an increasing incidence of breast cancer in women who have not yet completed their family. The current choice for premenopausal women with breast cancer is adjuvant therapy which includes cytotoxic chemotherapy, ovarian ablation (by surgery, irradiation, or chemical ovarian suppression), anti-estrogen therapy, or any combination of these. Although the use of adjuvant therapies with cytotoxic drugs can significantly reduce mortality, it raises issues of the long-term toxicity, such as induction of an early menopause and fertility impairment. The risk of infertility is a potential hardship to be faced by the patients following treatment of breast cancer. The offspring of patients who became pregnant after completion of chemotherapy have shown no adverse effects and congenital anomalies from the treatment, but sometimes high rates of abortion (29%) and premature deliveries with low birth weight (40%) have been demonstrated. Therefore, the issue of recent cytotoxic treatment remains controversial and further research is required to define a "safety period" between cessation of treatment and pregnancy. Preservation of fertility in breast cancer survivors of reproductive age has become an important issue regarding the quality of life. Currently, there are several potential options, including all available assisted technologies, such as in vitro fertilization and embryo transfer, in vitro maturation, oocyte and embryo cryopreservation, and cryopreservation of ovarian tissue. Because increased estrogen levels are thought to be potentially risky in breast cancer patients, recently developed ovarian stimulation protocols with the aromatase inhibitor letrozole and tamoxifen appear to provide safe stimulation with endogenous estrogen. Embryo cryopreservation seems to be the most established

  5. Triciribine Phosphate, Paclitaxel, Doxorubicin Hydrochloride, and Cyclophosphamide in Treating Patients With Stage IIB-IV Breast Cancer

    ClinicalTrials.gov

    2016-01-13

    Breast Adenocarcinoma; Estrogen Receptor Positive; HER2/Neu Negative; Recurrent Breast Carcinoma; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer

  6. Doxorubicin Hydrochloride and Cyclophosphamide Followed by Paclitaxel With or Without Carboplatin in Treating Patients With Triple-Negative Breast Cancer

    ClinicalTrials.gov

    2016-07-06

    Breast Adenocarcinoma; Estrogen Receptor Negative; HER2/Neu Negative; Progesterone Receptor Negative; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Stage IIIC Breast Cancer; Triple-Negative Breast Carcinoma

  7. Lipid-conjugated telomerase template antagonists sensitize resistant HER2-positive breast cancer cells to trastuzumab.

    PubMed

    Goldblatt, Erin M; Erickson, Priscilla A; Gentry, Erin R; Gryaznov, Sergei M; Herbert, Brittney-Shea

    2009-11-01

    HER2 amplification in breast cancer is associated with a more aggressive disease, greater likelihood of recurrence, and decreased survival compared to women with HER2-negative breast cancer. Trastuzumab is a monoclonal antibody that inhibits HER2 activity, making this compound an important therapeutic option for patients with HER2-positive breast cancer. However, resistance to trastuzumab develops rapidly in a large number of breast cancer patients. The objective of this study was to determine whether GRN163L, a telomerase template antagonist currently in clinical trials for cancer treatment, can augment the effects of trastuzumab in breast cancer cells with HER2 amplification. GRN163L was effective in inhibiting telomerase activity and shortening telomeres in HER2-positive breast cancer cells. We show that GRN163L acts synergistically with trastuzumab in inhibiting HER2-positive breast cancer cell growth. More importantly, we show that GRN163L can restore the sensitivity of therapeutic-resistant breast cancer cells to trastuzumab. These findings implicate that telomerase template antagonists have potential use in the treatment of cancers that have developed resistance to traditional cancer therapy. PMID:18853252

  8. Breast cancer and autism.

    PubMed

    Radcliff, Lisa

    2013-03-01

    Case Study Amy is a 44-year-old woman with severe autism. She lives with her sister Susan, who is her caregiver and guardian. Amy is ambulatory and able to dress and feed herself. She is a healthy individual with no other significant comorbidities. She walks daily and enjoys her sister's company. Amy's life expectancy is greater than 10 years. However, she is difficult to care for medically, as she will not allow a physical examination and strikes out when strangers try to touch her. She is nonverbal and unable to participate in decision-making. INITIAL DIAGNOSIS Amy has a history of breast cancer diagnosed 2 years ago, originally presenting as a stage I lesion (T2N0) that was palpated by her caregiver while bathing. She underwent right simple mastectomy with sentinel lymph node resection. Susan recalls that the mastectomy was a very challenging ordeal, as Amy kept pulling out IV lines, drains, and dressings. Susan felt that Amy withdrew from her after the procedure as she most likely associated Susan with the cause of the pain, making her role as caregiver more difficult. Pathology confirmed an invasive ductal carcinoma, moderately differentiated, 2.4 cm, estrogen/progesterone receptor negative, HER2/neu negative, with negative surgical margins. Two right axillary sentinel lymph nodes were negative for disease. The standard of care for a patient with these tumor features is surgery plus adjuvant chemotherapy (National Comprehensive Cancer Network [NCCN], 2012). According to the Adjuvant Online! database (2012), Amy's risk for relapse was approximately 40% without adjuvant treatment; her risk for mortality was approximately 29%. After meeting with a medical oncologist, Amy did not receive adjuvant chemotherapy. According to Susan, she was not offered the choice, and the decision was not explained to them. She was simply told that it was not necessary. Aside from pathology, previous records were unavailable for review. Medical assessment of Amy's level of autism

  9. Noncoding RNAs in breast cancer.

    PubMed

    Lo, Pang-Kuo; Wolfson, Benjamin; Zhou, Xipeng; Duru, Nadire; Gernapudi, Ramkishore; Zhou, Qun

    2016-05-01

    The mammalian transcriptome has recently been revealed to encompass a large number of noncoding RNAs (ncRNAs) that play a variety of important regulatory roles in gene expression and other biological processes. MicroRNAs (miRNAs), the best studied of the short noncoding RNAs (sncRNAs), have been extensively characterized with regard to their biogenesis, function and importance in tumorigenesis. Another class of sncRNAs called piwi-interacting RNAs (piRNAs) has also gained attention recently in cancer research owing to their critical role in stem cell regulation. Long noncoding RNAs (lncRNAs) of >200 nucleotides in length have recently emerged as key regulators of developmental processes, including mammary gland development. lncRNA dysregulation has also been implicated in the development of various cancers, including breast cancer. In this review, we describe and discuss the roles of sncRNAs (including miRNAs and piRNAs) and lncRNAs in the initiation and progression of breast tumorigenesis, with a focus on outlining the molecular mechanisms of oncogenic and tumor-suppressor ncRNAs. Moreover, the current and potential future applications of ncRNAs to clinical breast cancer research are also discussed, with an emphasis on ncRNA-based diagnosis, prognosis and future therapeutics. PMID:26685283

  10. What Are the Risk Factors for Breast Cancer in Men?

    MedlinePlus

    ... in men? What are the risk factors for breast cancer in men? A risk factor is anything that ... old when they are diagnosed. Family history of breast cancer Breast cancer risk is increased if other members ...

  11. Early-Stage Breast Cancer Treatment Fact Sheet

    MedlinePlus

    ... breast cancer treatment fact sheet ePublications Early-stage breast cancer treatment fact sheet Print this fact sheet Early-stage breast cancer treatment fact sheet (PDF, 943 KB) Related information ...

  12. Can Breast Cancer in Men Be Found Early?

    MedlinePlus

    ... and symptoms of breast cancer in men Can breast cancer in men be found early? Early detection improves ... be treated successfully. Differences affecting early detection of breast cancers in men and women There are many similarities ...

  13. Ten Years of Tamoxifen Reduces Breast Cancer Recurrences, Improves Survival

    MedlinePlus

    ... Cancer Screening Research Ten Years of Tamoxifen Reduces Breast Cancer Recurrences, Improves Survival For some women with breast ... took it for 5 years. (See the table.) Breast Cancer Recurrence and Death 5 to 14 Years after ...

  14. NIH study confirms risk factors for male breast cancer

    Cancer.gov

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

  15. [Influences and psychological structures in breast cancer].

    PubMed

    Bucher, R; Rodovalho, J C; Ferreira, T C

    1986-12-01

    A sample of 16 patients with malignant breast tumors were examined by means of an interview, a questionnaire, and the Szondi Test together with a comparison group of 56 patients with benign breast tumors. The patients were divided into two age groups, those below and above 40 years of age. In this way studies done in other countries to investigate the personality structure of cancer patients were replicated. Emphasis was given to the following issues: self-destructive and/or masochistic tendencies, attitudes of depressive resignation, and conflicts with respect to femininity and motherhood. The results showed several significant differences by which benign tumor patients can be better characterized. These patients presented symptoms, experiences and structures of the neurotic type. The cancer patients presented structures closer to the psychosomatic type, with rigid negation of conflicts (in relation to sex, identification, violence and aggression), and with an unreal insertion in the world. Their somatizations are not conversive; they are interpreted as effects of the destructive and violent tendencies which, without release for the lack of adequate contacts with objects, are directed toward themselves. However, this cannot properly be called a masochistic structure because the destructive tendencies do not have a sexual origin, rather they are part of a vehement negation of others and of life itself, in the sense of a primary death drive. It is impossible to tell, however, to what point these characteristics are already the effects of the breast problems, or whether they have more causal relevance as certain previous personal experiences indicate. PMID:3591399

  16. Electric power, melatonin, and breast cancer

    SciTech Connect

    Stevens, R.G.

    1987-08-01

    In this paper, the epidemiology of breast cancer will be discussed, followed by a brief description of the effect of electric fields on melatonin and the relation of melatonin to mammary cancer in rats. Finally, there will be a consideration of factors such as alcohol that affect melatonin and their relation to breast cancer risk. 55 refs.

  17. Selected National Cancer Institute Breast Cancer Research Topics | NIH MedlinePlus the Magazine

    MedlinePlus

    ... Sciences are jointly funding three Breast Cancer and Environment Research Centers (BCERCs) to conduct interdisciplinary research on the effects of early environmental exposures on breast development and breast cancer risk. The Breast Cancer Surveillance ...

  18. Environmental cadmium and breast cancer risk

    PubMed Central

    Gallagher, Carolyn M.; Chen, John J.; Kovach, John S.

    2010-01-01

    Breast cancer is the most prevalent women's cancer, with an age-adjusted incidence of 122.9 per 100,000 US women. Cadmium, a ubiquitous carcinogenic pollutant with multiple biological effects, has been reported to be associated with breast cancer in one US regional case-control study. We examined the association of breast cancer with urinary cadmium (UCd), in a case-control sample of women living on Long Island (LI), NY (100 with breast cancer and 98 without), a region with an especially high rate of breast cancer (142.7 per 100,000 in Suffolk County) and in a representative sample of US women (NHANES 1999-2008, 92 with breast cancer and 2,884 without). In a multivariable logistic model, both samples showed a significant trend for increased odds of breast cancer across increasing UCd quartiles (NHANES, p=0.039 and LI, p=0.023). Compared to those in the lowest quartile, LI women in the highest quartile had increased risk for breast cancer (OR=2.69; 95% CI=1.07, 6.78) and US women in the two highest quartiles had increased risk (OR=2.50; 95% CI=1.11, 5.63 and OR=2.22; 95% CI=.89, 5.52, respectively). Further research is warranted on the impact of environmental cadmium on breast cancer risk in specific populations and on identifying the underlying molecular mechanisms. PMID:21071816

  19. Diet and risk of breast cancer

    PubMed Central

    2016-01-01

    Diet may play a role in both promoting and inhibiting human breast cancer development. In this review, nutritional risk factors such as consumption of dietary fat, meat, fiber, and alcohol, and intake of phytoestrogen, vitamin D, iron, and folate associated with breast cancer are reviewed. These nutritional factors have a variety of associations with breast cancer risk. Type of fat consumed has different effects on risk of breast cancer: consumption of meat is associated with heterocyclic amine (HCA) exposure; different types of plant fiber have various effects on breast cancer risk; alcohol consumption may increase the risk of breast cancer by producing acetaldehyde and reactive oxygen species (ROS); intake of phytoestrogen may reduce risk of breast cancer through genomic and non-genomic action; vitamin D can reduce the risk of breast cancer by inhibiting the process of cancer invasion and metastasis; intake of dietary iron may lead to oxidative stress, DNA damage, and lipid peroxidation; and lower intake of folate may be linked to a higher risk of breast cancer. PMID:27095934

  20. Diet and risk of breast cancer.

    PubMed

    Kotepui, Manas

    2016-01-01

    Diet may play a role in both promoting and inhibiting human breast cancer development. In this review, nutritional risk factors such as consumption of dietary fat, meat, fiber, and alcohol, and intake of phytoestrogen, vitamin D, iron, and folate associated with breast cancer are reviewed. These nutritional factors have a variety of associations with breast cancer risk. Type of fat consumed has different effects on risk of breast cancer: consumption of meat is associated with heterocyclic amine (HCA) exposure; different types of plant fiber have various effects on breast cancer risk; alcohol consumption may increase the risk of breast cancer by producing acetaldehyde and reactive oxygen species (ROS); intake of phytoestrogen may reduce risk of breast cancer through genomic and non-genomic action; vitamin D can reduce the risk of breast cancer by inhibiting the process of cancer invasion and metastasis; intake of dietary iron may lead to oxidative stress, DNA damage, and lipid peroxidation; and lower intake of folate may be linked to a higher risk of breast cancer. PMID:27095934

  1. What Are the Key Statistics about Breast Cancer in Men?

    MedlinePlus

    ... breast cancer in men? What are the key statistics about breast cancer in men? The American Cancer ... 30 years. Visit the American Cancer Society’s Cancer Statistics Center for more key statistics. Last Medical Review: ...

  2. Skp2 is over-expressed in breast cancer and promotes breast cancer cell proliferation.

    PubMed

    Zhang, Wenwen; Cao, Lulu; Sun, Zijia; Xu, Jing; Tang, Lin; Chen, Weiwei; Luo, Jiayan; Yang, Fang; Wang, Yucai; Guan, Xiaoxiang

    2016-05-18

    The F box protein Skp2 is oncogenic. Skp2 and Skp2B, an isoform of Skp2 are overexpressed in breast cancer. However, little is known regarding the mechanism by which Skp2B promotes the occurrence and development of breast cancer. Here, we determined the expression and clinical outcomes of Skp2 in breast cancer samples and cell lines using breast cancer database, and investigated the role of Skp2 and Skp2B in breast cancer cell growth, apoptosis and cell cycle arrest. We obtained Skp2 is significantly overexpressed in breast cancer samples and cell lines, and high Skp2 expression positively correlated with poor prognosis of breast cancer. Both Skp2 and Skp2B could promote breast cancer cell proliferation, inhibit cell apoptosis, change the cell cycle distribution and induce the increased S phase cells and therefore induce cell proliferation in breast cancer cells. Moreover, the 2 isoforms could both suppress PIG3 expression via independent pathways in the breast cancer cells. Skp2 suppressed p53 and inhibited PIG3-induced apoptosis, while Skp2B attenuated the function of PIG3 by inhibiting PHB. Our results indicate that Skp2 and Skp2B induce breast cancer cell development and progression, making Skp2 and Skp2B potential molecular targets for breast cancer therapy. PMID:27111245

  3. Pregnancy-associated breast cancer.

    PubMed

    Keinan-Boker, Lital; Lerner-Geva, Liat; Kaufman, Bella; Meirow, Dror

    2008-10-01

    The frequency of pregnancy-associated breast cancer, a rare but serious occurrence, may increase in light of the secular trends for lower parity in general and for older age at first full-term delivery in particular Data on PABC in individuals who are at high risk for breast cancer are limited. A computerized search of Pubmed showed that the reported incidence of PABC is 1:3000 pregnancies; it is often diagnosed at an advanced stage and its prognosis is inferior compared to non-PABC Carriers of mutations in the genes BRCA1/2 may present a specific high risk group for PABC especially at younger ages. Women treated with fertility treatment drugs may be at a higher risk for PABC as well. PMID:19009954

  4. MK2206 in Treating Patients With Stage I, Stage II, or Stage III Breast Cancer

    ClinicalTrials.gov

    2015-03-16

    Estrogen Receptor Negative; Estrogen Receptor Positive; HER2/Neu Negative; HER2/Neu Positive; Progesterone Receptor Negative; Progesterone Receptor Positive; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Triple-Negative Breast Carcinoma

  5. Educational Counseling in Improving Communication and Quality of Life in Spouses and Breast Cancer Patients

    ClinicalTrials.gov

    2014-12-29

    Anxiety Disorder; Depression; Ductal Breast Carcinoma in Situ; Lobular Breast Carcinoma in Situ; Psychosocial Effects of Cancer and Its Treatment; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

  6. Denbinobin suppresses breast cancer metastasis through the inhibition of Src-mediated signaling pathways.

    PubMed

    Chen, Pei-Hsuan; Peng, Chieh-Yu; Pai, Hui-Chen; Teng, Che-Ming; Chen, Chien-Chih; Yang, Chia-Ron

    2011-08-01

    Denbinobin (5-hydroxy-3,7-dimethoxy- 1,4-phenanthraquinone), a biologically active chemical isolated from Ephemerantha lonchophylla, has been demonstrated to display anti-cancer activity. Breast cancer is the leading cause of female mortality, and the high mortality is mainly attributable to metastasis. Src kinase activity is elevated in many human cancers, including breast cancer, and is often associated with aggressive disease. In the present study, we examined the anti-metastatic effects of denbinobin through decreasing Src kinase activity in human and mouse breast cancer cells. Denbinobin caused significant block of Src kinase activity in both human and mouse breast cancer cells. Moreover, phosphorylation of the signaling molecules focal adhesion kinase, Crk-associated substrate and paxillin downstream of Src was also inhibited by denbinobin. Furthermore, denbinobin inhibited the in vitro migration, invasion and in vivo metastasis of breast cancers in a mouse metastatic model. The denbinobin-treated group showed a significant reduction in tumor metastasis, orthrotopic tumor volume, and spleen enlargement compared to the control group. In addition, transfection of breast cancer cells with a plasmid coding for a constitutively active Src prevented the denbinobin-mediated phosphorylation of Src and downstream molecules and cell migration. Our findings provide evidences that denbinobin inhibits Src-mediated signaling pathways involved in controlling breast cancer migration and metastasis, suggesting that it has therapeutic potential in breast cancer treatment. PMID:21062671

  7. [Treatment of disseminated breast cancer].

    PubMed

    Mattson, Johanna; Huovinen, Riikka

    2015-01-01

    Although several effective drugs have in recent years been introduced for the treatment of disseminated breast cancer, it is still an incurable illness. Many patients live a fairly normal life with their illness for a long time, and some of them are able to continue working in spite of the therapies. Factors considered in tailoring the treatment include tumor subtype, extent of the disease, symptoms, previous treatments and the achieved treatment outcome, and adverse effects of the treatments. PMID:26245064

  8. Using hair to screen for breast cancer

    NASA Astrophysics Data System (ADS)

    James, Veronica; Kearsley, John; Irving, Tom; Amemiya, Yoshiyuki; Cookson, David

    1999-03-01

    We have studied hair using fibre X-ray diffraction studies with synchrotron radiation and find that hair from breast-cancer patients has a different intermolecular structure to hair from healthy subjects. These changes are seen in all samples of scalp and pubic hair taken from women diagnosed with breast cancer. All the hair samples from women who tested positive for a mutation of the BRCA1 gene, which is associated with a higher risk of breast cancer, also show these changes. Because our results are so consistent, we propose that such hair analyses may be used as a simple, non-invasive screening method for breast cancer.

  9. [Systemic therapy of breast cancer: practice guideline].

    PubMed

    Horváth, Zsolt; Boér, Katalin; Dank, Magdolna; Kahán, Zsuzsanna; Kocsis, Judit; Kövér, Erika; Pajkos, Gábor; Pikó, Béla; Rubovszky, Gábor; Eckhardt, Sándor

    2016-09-01

    The article presents the practice guideline of systemic treatment of breast cancer and recommendations of the 3rd Hungarian Breast Cancer Consensus Conference. It reflects the recent international guidelines (ESMO, NCCN, ABC2, St Gallen's) irrespectively of the current financial opportunities. Here we follow the early - locally advanced - locally relapsed - metastatic breast cancer line for didactic considerations and we discuss the different subgroups of breast cancer based on hormone receptor and HER2 receptor status. Diagnosis and treatment options of rare clinical entities are summarised at the end of the paper. PMID:27579723

  10. Breast cancer and the consumption of coffee.

    PubMed

    Rosenberg, L; Miller, D R; Helmrich, S P; Kaufman, D W; Schottenfeld, D; Stolley, P D; Shapiro, S

    1985-09-01

    The hypothesis has been raised that coffee consumption may increase the incidence of breast cancer, based on the report that fibrocystic breast disease, a risk factor for breast cancer, regresses after abstention from coffee and other methylxanthines. The relation between recent coffee consumption and the risk of breast cancer was evaluated in a case-control study, based on interviews conducted 1975-1982 at several mainly eastern US teaching and community hospitals. The responses of 2,651 women with newly diagnosed breast cancer were compared with those of 1,501 controls with nonmalignant conditions and 385 controls with cancers at other sites. The relative risk estimates for levels of coffee drinking up to seven or more cups daily, relative to none, approximated 1.0 with narrow 95% confidence intervals. After allowance for confounding, the relative risk estimate for drinking at least five cups a day was 1.2 (95% confidence interval, 0.9-1.6) using the noncancer controls and 1.1 (0.7-1.6) using the cancer controls. Coffee consumption was not associated with an increase in the risk of breast cancer among women with a history of fibrocystic breast disease, nor were tea or decaffeinated coffee associated with an increase in the risk of breast cancer. The results suggest that the recent consumption of coffee does not influence the incidence of breast cancer. PMID:4025289

  11. Carboplatin, Gemcitabine Hydrochloride, and Mifepristone in Treating Patients With Advanced Breast Cancer or Recurrent or Persistent Ovarian Epithelial, Fallopian Tube, or Primary Peritoneal Cancer

    ClinicalTrials.gov

    2016-03-31

    Male Breast Cancer; Recurrent Breast Cancer; Recurrent Fallopian Tube Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Primary Peritoneal Cavity Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer

  12. Breast Cancer 2012 - New Aspects.

    PubMed

    Kolberg, H-C; Lüftner, D; Lux, M P; Maass, N; Schütz, F; Fasching, P A; Fehm, T; Janni, W; Kümmel, S

    2012-07-01

    Treatment options as well as the characteristics for therapeutic decisions in patients with primary and advanced breast cancer are increasing in number and variety. New targeted therapies in combination with established chemotherapy schemes are broadening the spectrum, however potentially promising combinations do not always achieve a better result. New data from the field of pharmacogenomics point to prognostic and predictive factors that take not only the properties of the tumour but also inherited genetic properties of the patient into consideration. Current therapeutic decision-making is thus based on a combination of classical clinical and modern molecular biomarkers. Also health-economic aspects are more frequently being taken into consideration so that health-economic considerations may also play a part. This review is based on information from the recent annual congresses. The latest of these are the 34th San Antonio Breast Cancer Symposium 2011 and the ASCO Annual Meeting 2012. Among their highlights are the clinically significant results from the CLEOPATRA, BOLERO-2, EMILIA and SWOG S0226 trials on the therapy for metastatic breast cancer as well as further state-of-the-art data on the adjuvant use of bisphosphonates within the framework of the ABCSG-12, ZO-FAST, NSABP-B34 and GAIN trials. PMID:25324576

  13. Breast Cancer Research at NASA

    NASA Technical Reports Server (NTRS)

    1998-01-01

    Epithelial and fibroblast cell coculture: Long-term growth human mammary epithelial cells (HMEC) admixed in coculture with fibroblast from the same initial breast tissue grown as 3-dimenstional constructions in the presence of attachment beads in the NASA Bioreactor. A: A typical constrct about 2.0 mm in diameter without beads on the surface. The center of these constrcts is hollow, and beads are organized about the irner surface. Although the coculture provides smaller constructs than the monoculture, the metabolic of the organized cells is about the same. B, C, D: Closer views of cells showing that the shape of cells and cell-to-cell interactions apprear different in the coculture than in the monoculture constructs. NASA's Marshall Space Flight Center (MSFC) is sponsoring research with Bioreactors, rotating wall vessels designed to grow tissue samples in space, to understand how breast cancer works. This ground-based work studies the growth and assembly of human mammary epithelial cell (HMEC) from breast cancer susceptible tissue. Radiation can make the cells cancerous, thus allowing better comparisons of healthy vs. tunorous tissue. Credit: Dr. Robert Richmond, NASA/Marshall Space Flight Center (MSFC).

  14. Intractable pain with breast cancer.

    PubMed Central

    Watson, C. P.; Evans, R. J.

    1982-01-01

    This study examines retrospectively the cause, clinical features, natural history and results of treatment of intractable pain associated with breast cancer in 210 patients. The three chief types of pain were that due to skeletal metastases or brachial plexus neuropathy and pain of psychogenic origin. Onset at the time of cancer diagnosis characterized the psychogenic pain, whereas pain from metastases first occurred after a median latency of 3.7 years. Treatment was custom-tailored to the specific patient and pain problem, with several factors taken into account. The onset of intractable pain due to metastatic disease indicated a short survival (median, 9 months). PMID:6277445

  15. Typhoid Vaccine in Testing Response to Immune Stress in Patients With Stage I-IIIA Breast Cancer Who Received Chemotherapy

    ClinicalTrials.gov

    2016-04-15

    Cognitive Side Effects of Cancer Therapy; Depression; Recurrent Breast Carcinoma; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer

  16. Adolescent meat intake and breast cancer risk.

    PubMed

    Farvid, Maryam S; Cho, Eunyoung; Chen, Wendy Y; Eliassen, A Heather; Willett, Walter C

    2015-04-15

    The breast is particularly vulnerable to carcinogenic influences during adolescence due to rapid proliferation of mammary cells and lack of terminal differentiation. We investigated consumption of adolescent red meat and other protein sources in relation to breast cancer risk in the Nurses' Health Study II cohort. We followed prospectively 44,231 women aged 33-52 years who, in 1998, completed a detailed questionnaire about diet during adolescence. Relative risks (RR) and 95% confidence intervals (95%CI) were estimated using Cox proportional hazard regression. We documented 1132 breast cancer cases during 13-year follow-up. In multivariable Cox regression models with major breast cancer risk factors adjustment, greater consumption of total red meat in adolescence was significantly associated with higher premenopausal breast cancer risk (highest vs. lowest quintiles, RR, 1.43; 95%CI, 1.05-1.94; Ptrend  = 0.007), but not postmenopausal breast cancer. Adolescent intake of poultry was associated with lower risk of breast cancer overall (RR, 0.76; 95%CI, 0.60-0.97; for each serving/day). Adolescent intakes of iron, heme iron, fish, eggs, legumes and nuts were not associated with breast cancer. Replacement of one serving/day of total red meat with one serving of combination of poultry, fish, legumes, and nuts was associated with a 15% lower risk of breast cancer overall (RR, 0.85; 95%CI, 0.74-0.96) and a 23% lower risk of premenopausal breast cancer (RR, 0.77; 95%CI, 0.64-0.92). In conclusion, higher consumption of red meat during adolescence was associated with premenopausal breast cancer. Substituting other dietary protein sources for red meat in adolescent diet may decrease premenopausal breast cancer risk. PMID:25220168

  17. New trends in breast cancer surgery: a therapeutic approach increasingly efficacy and respectful of the patient

    PubMed Central

    FRANCESCHINI, G.; SANCHEZ, A. MARTIN; DI LEONE, A.; MAGNO, S.; MOSCHELLA, F.; ACCETTA, C.; MASETTI, R.

    2015-01-01

    The surgical management of breast cancer has undergone continuous and profound changes over the last 40 years. The evolution from aggressive and mutilating treatment to conservative approach has been long, but constant, despite the controversies that appeared every time a new procedure came to light. Today, the aesthetic satisfaction of breast cancer patients coupled with the oncological safety is the goal of the modern breast surgeon. Breast-conserving surgery with adjuvant radiotherapy is considered the gold standard approach for patients with early stage breast cancer and the recent introduction of “oncoplastic techniques” has furtherly increased the use of breast-conserving procedures. Mastectomy remains a valid surgical alternative in selected cases and is usually associated with immediate reconstructive procedures. New surgical procedures called “conservative mastectomies” are emerging as techniques that combine oncological safety and cosmesis by entirely removing the breast parenchyma sparing the breast skin and nipple-areola complex. Staging of the axilla has also gradually evolved toward less aggressive approaches with the adoption of sentinel node biopsy and new therapeutic strategies are emerging in patients with a pathological positivity in sentinel lymph node biopsy. The present work will highlight the new surgical treatment options increasingly efficacy and respectful of breast cancer patients. PMID:26712068

  18. [THE EFFECT OF PREGNANCY ON BREAST CANCER].

    PubMed

    Matalon, Shelly Tartakover; Shochet, Gali Epstein; Drucker, Liat; Lishner, Michael

    2015-08-01

    Cancer and pregnancy coincide in about one in 1,000 pregnancies. One of the most common malignancies associated with pregnancy is breast cancer. Women with pregnancy-associated breast cancer (PABC) have a higher likelihood of being diagnosed with metastatic disease and estrogen receptor (ER) negative tumors than do non-pregnant women. Controversies exist regarding the effect of pregnancy on breast cancer prognosis. Some researchers suggest that pregnancy does not affect breast cancer prognosis, whereas others claim the opposite. Although PABC is usually discovered in an advanced stage, breast cancer metastasis on the placenta is a rare event. During cancer progression, the surrounding microenvironment co-evolves into an activated state through continuous communication with the malignant cells, thereby promoting tumor growth. The effect of pregnancy and placental environment on breast cancer biology is the issue of this review. Placental and cancer cells implantation processes share similar molecular pathways. This suggests that placental factors may affect breast cancer cells biology. Previously, we analyzed the effect of first trimester human placenta on breast cancer cells. Breast cancer cells were co-cultured with placental explants during their implantation on matrigel substrate. We found that the placenta reduced ER expression on the cancer cells and induced their migration and invasion abilities. As a result of it, breast cancer cells migrated away from the placental implantation sites. Hormonal pathways were involved in these phenomena. These results may explain the high incidence of metastases during pregnancy in on the one hand and the rarity of metastases on the placenta on the other hand. PMID:26480621

  19. Gene Tied to Breast Cancer Raises Uterine Cancer Risk Too

    MedlinePlus

    ... news/fullstory_159652.html Gene Tied to Breast Cancer Raises Uterine Cancer Risk Too Women with BRCA1 may want to ... increased risk for a deadly form of uterine cancer, a new study finds. The BRCA1 gene mutation ...

  20. Radiation Therapy in Treating Post-Menopausal Women With Early Stage Breast Cancer Undergoing Surgery

    ClinicalTrials.gov

    2015-09-02

    Ductal Breast Carcinoma In Situ; Estrogen Receptor Negative; Estrogen Receptor Positive; HER2/Neu Negative; Invasive Cribriform Breast Carcinoma; Invasive Ductal Carcinoma, Not Otherwise Specified; Lobular Breast Carcinoma In Situ; Mucinous Breast Carcinoma; Papillary Breast Carcinoma; Progesterone Receptor Positive; Stage I Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIC Breast Cancer; Tubular Breast Carcinoma

  1. Intraoperative radiotherapy for breast cancer

    PubMed Central

    Williams, Norman R.; Pigott, Katharine H.; Brew-Graves, Chris

    2014-01-01

    Intra-operative radiotherapy (IORT) as a treatment for breast cancer is a relatively new technique that is designed to be a replacement for whole breast external beam radiotherapy (EBRT) in selected women suitable for breast-conserving therapy. This article reviews twelve reasons for the use of the technique, with a particular emphasis on targeted intra-operative radiotherapy (TARGIT) which uses X-rays generated from a portable device within the operating theatre immediately after the breast tumour (and surrounding margin of healthy tissue) has been removed. The delivery of a single fraction of radiotherapy directly to the tumour bed at the time of surgery, with the capability of adding EBRT at a later date if required (risk-adaptive technique) is discussed in light of recent results from a large multinational randomised controlled trial comparing TARGIT with EBRT. The technique avoids irradiation of normal tissues such as skin, heart, lungs, ribs and spine, and has been shown to improve cosmetic outcome when compared with EBRT. Beneficial aspects to both institutional and societal economics are discussed, together with evidence demonstrating excellent patient satisfaction and quality of life. There is a discussion of the published evidence regarding the use of IORT twice in the same breast (for new primary cancers) and in patients who would never be considered for EBRT because of their special circumstances (such as the frail, the elderly, or those with collagen vascular disease). Finally, there is a discussion of the role of the TARGIT Academy in developing and sustaining high standards in the use of the technique. PMID:25083504

  2. Women with Breast Cancer Micrometastases in Their Sentinel Lymph Nodes May Not Need Axillary Dissection

    MedlinePlus

    ... and data sets for researchers Research by Cancer Type Find research about a specific cancer type Progress Annual Report ... Laws Careers Visitor Information Search Search Home Cancer Types Breast Cancer Research Breast Cancer Patient Breast Cancer Treatment Male Breast ...

  3. Breast Cancer Detection

    NASA Technical Reports Server (NTRS)

    1976-01-01

    NASA's Jet Propulsion Laboratory has come up with a technique to decrease exposure to harmful x-rays in mammographies or breast radiography. Usually, physicians make more than one exposure to arrive at an x-ray film of acceptable density. Now the same solar cells used to convert sunlight into electricity on space satellites can make a single exposure sufficient. When solar cell sensor is positioned directly beneath x-ray film, it can determine exactly when film has received sufficient radiation and has been exposed to optimum density. At that point associated electronic equipment sends signal to cut off x-ray source. Reduction of mammography to single exposures not only reduced x-ray hazard significantly, but doubled the number of patient examinations handled by one machine. The NASA laboratory used this control system at the Huntington Memorial Hospital with overwhelming success.

  4. Sub-100nm gold nanomatryoshkas improve photo-thermal therapy efficacy in large and highly aggressive triple negative breast tumors.

    PubMed

    Ayala-Orozco, Ciceron; Urban, Cordula; Bishnoi, Sandra; Urban, Alexander; Charron, Heather; Mitchell, Tamika; Shea, Martin; Nanda, Sarmistha; Schiff, Rachel; Halas, Naomi; Joshi, Amit

    2014-10-10

    There is an unmet need for efficient near-infrared photothermal transducers for the treatment of highly aggressive cancers and large tumors where the penetration of light can be substantially reduced, and the intra-tumoral nanoparticle transport is restricted due to the presence of hypoxic or necrotic regions. We report the performance advantages obtained by sub 100nm gold nanomatryushkas, comprising concentric gold-silica-gold layers compared to conventional ~150nm silica core gold nanoshells for photothermal therapy of triple negative breast cancer. We demonstrate that a 33% reduction in silica-core-gold-shell nanoparticle size, while retaining near-infrared plasmon resonance, and keeping the nanoparticle surface charge constant, results in a four to five fold tumor accumulation of nanoparticles following equal dose of injected gold for both sizes. The survival time of mice bearing large (>1000mm(3)) and highly aggressive triple negative breast tumors is doubled for the nanomatryushka treatment group under identical photo-thermal therapy conditions. The higher absorption cross-section of a nanomatryoshka results in a higher efficiency of photonic to thermal energy conversion and coupled with 4-5× accumulation within large tumors results in superior therapy efficacy. PMID:25051221

  5. Sub-100 nm Gold Nanomatryoshkas Improve Photo-thermal Therapy Efficacy in Large and Highly Aggressive Triple Negative Breast Tumors

    PubMed Central

    Bishnoi, Sandra; Urban, Alexander; Charron, Heather; Mitchell, Tamika; Shea, Martin; Nanda, Sarmistha; Schiff, Rachel; Halas, Naomi; Joshi, Amit

    2014-01-01

    There is an unmet need for efficient near-infrared photothermal transducers for the treatment of highly aggressive cancers and large tumors where the penetration of light can be substantially reduced, and the intra-tumoral nanoparticle transport is restricted due to the presence of hypoxic or nectrotic regions. We report the performance advantages obtained by sub 100 nm gold nanomatryushkas, comprising of concentric gold-silica-gold layers compared to conventional ~150 nm silica core gold nanoshells for photothermal therapy of triple negative breast cancer. We demonstrate that a 33% reduction in silica-core-gold-shell nanoparticle size, while retaining near-infrared plasmon resonance, and keeping the nanoparticle surface charge constant, results in a four to five fold tumor accumulation of nanoparticles following equal dose of injected gold for both sizes. The survival time of mice bearing large (>1000 mm3) and highly aggressive triple negative breast tumors is doubled for the nanomatryushka treatment group under identical photo-thermal therapy conditions. The higher absorption cross-section of a nanomatryoshka results in a higher efficiency of photonic to thermal energy conversion and coupled with 4-5X accumulation within large tumors results in superior therapy efficacy. PMID:25051221

  6. Male breast cancer: is the scenario changing

    PubMed Central

    Contractor, Kaiyumars B; Kaur, Kanchan; Rodrigues, Gabriel S; Kulkarni, Dhananjay M; Singhal, Hemant

    2008-01-01

    Background The overall incidence of male breast cancer is around 1% of all breast cancers and is on the rise. In this review we aim to present various aspects of male breast cancer with particular emphasis on incidence, risk factors, patho-physiology, treatment, prognostic factors, and outcome. Methods Information on all aspects of male breast cancer was gathered from available relevant literature on male breast cancer from the MEDLINE database over the past 32 years from 1975 to 2007. Various reported studies were scrutinized for emerging evidence. Incidence data were also obtained from the IARC, Cancer Mondial database. Conclusion There is a scenario of rising incidence, particularly in urban US, Canada and UK. Even though more data on risk factors is emerging about this disease, more multi-institutional efforts to pool data with large randomized trials to show treatment and survival benefits are needed to support the existing vast emerging knowledge about the disease. PMID:18558006

  7. Genetics and molecular biology of breast cancer

    SciTech Connect

    King, M.C.; Lippman, M.

    1992-12-31

    This volume contains the abstracts of oral presentations and poster sessions presented at the Cold Springs Harbor Meeting on Cancer Cells, this meeting entitled Genetics and Molecular Biology of Breast Cancer.

  8. TP53 genetic alterations in Arab breast cancer patients: Novel mutations, pattern and distribution

    PubMed Central

    AL-QASEM, ABEER J.; TOULIMAT, MOHAMED; ELDALI, ABDELMONEIM M.; TULBAH, ASMA; AL-YOUSEF, NUJOUD; AL-DAIHAN, SOOAD K.; AL-TASSAN, NADA; AL-TWEIGERI, TAHER; ABOUSSEKHRA, ABDELILAH

    2011-01-01

    Breast cancer remains a worldwide public health concern. The incidence and mortality of breast cancer varies significantly in ethnically and geographically distinct populations. In the Kingdom of Saudi Arabia (KSA) breast cancer has shown an increase in incidence and is characterized by early onset and aggressiveness. The tumor suppressor TP53 gene is a crucial genetic factor that plays a significant role in breast carcinogenesis. Furthermore, studies have shown a correlation between certain p53 mutations and response to therapy in breast cancer. In the present study, TP53 mutations were identified by direct sequencing of the gene (exons 4–9) from 119 breast cancer tissues. The prevalence of TP53 mutations in Arab breast cancer patients living in the KSA is among the highest in the world (40%). Notably, 73% of the patients whose tumors harbored p53 mutations were less than 50 years of age. Furthermore, for the first time, we identified 7 novel mutations and 16 mutations in breast cancer tissues. Notably, all the novel point mutations were found in exon 4, wherein 29% of the mutations were localized. Furthermore, an excess of G:C→A:T transitions (49%) at non-CpG sites was noted, suggesting exposure to particular environmental carcinogens such as N-nitroso compounds. The results indicate that the TP53 gene plays a significant role in breast carcinogenesis and the early onset of the disease among Arab female individuals. PMID:22866089

  9. TP53 genetic alterations in Arab breast cancer patients: Novel mutations, pattern and distribution.

    PubMed

    Al-Qasem, Abeer J; Toulimat, Mohamed; Eldali, Abdelmoneim M; Tulbah, Asma; Al-Yousef, Nujoud; Al-Daihan, Sooad K; Al-Tassan, Nada; Al-Tweigeri, Taher; Aboussekhra, Abdelilah

    2011-03-01

    Breast cancer remains a worldwide public health concern. The incidence and mortality of breast cancer varies significantly in ethnically and geographically distinct populations. In the Kingdom of Saudi Arabia (KSA) breast cancer has shown an increase in incidence and is characterized by early onset and aggressiveness. The tumor suppressor TP53 gene is a crucial genetic factor that plays a significant role in breast carcinogenesis. Furthermore, studies have shown a correlation between certain p53 mutations and response to therapy in breast cancer. In the present study, TP53 mutations were identified by direct sequencing of the gene (exons 4-9) from 119 breast cancer tissues. The prevalence of TP53 mutations in Arab breast cancer patients living in the KSA is among the highest in the world (40%). Notably, 73% of the patients whose tumors harbored p53 mutations were less than 50 years of age. Furthermore, for the first time, we identified 7 novel mutations and 16 mutations in breast cancer tissues. Notably, all the novel point mutations were found in exon 4, wherein 29% of the mutations were localized. Furthermore, an excess of G:C→A:T transitions (49%) at non-CpG sites was noted, suggesting exposure to particular environmental carcinogens such as N-nitroso compounds. The results indicate that the TP53 gene plays a significant role in breast carcinogenesis and the early onset of the disease among Arab female individuals. PMID:22866089

  10. Mammographic breast density: effect on imaging and breast cancer risk.

    PubMed

    Pinsky, Renee W; Helvie, Mark A

    2010-10-01

    Mammographic breast density has been studied for more than 30 years. Greater breast density not only is related to decreased sensitivity of mammograms because of a masking effect but also is a major independent risk factor for breast cancer. This article defines breast density and reviews literature on quantification of mammographic density that is key to future clinical and research protocols. Important influences on breast density are addressed, including age, menopausal status, exogenous hormones, and genetics of density. Young women with dense breasts benefit from digital mammographic technique. The potential use of supplemental MRI and ultrasound screening techniques in high-risk women and women with dense breasts is explored, as are potential risk reduction strategies. PMID:20971840

  11. 0927GCC: Entinostat and Anastrozole in Treating Postmenopausal Women With Triple-Negative Breast Cancer That Can Be Removed by Surgery

    ClinicalTrials.gov

    2016-03-01

    Estrogen Receptor-negative Breast Cancer; HER2-negative Breast Cancer; Progesterone Receptor-negative Breast Cancer; Stage I Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Triple-negative Breast Cancer

  12. Carboplatin and Paclitaxel Albumin-Stabilized Nanoparticle Formulation Before Surgery in Treating Patients With Locally Advanced or Inflammatory Triple Negative Breast Cancer

    ClinicalTrials.gov

    2016-07-14

    Inflammatory Breast Cancer; Stage IIA Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Triple-negative Breast Cancer; Stage IIB Breast Cancer; Estrogen Receptor Negative; Progesterone Receptor Negative; HER2/Neu Negative

  13. Palbociclib in Combination With Tamoxifen as First Line Therapy for Metastatic Hormone Receptor Positive Breast Cancer

    ClinicalTrials.gov

    2016-07-05

    Hormone Receptor Positive Malignant Neoplasm of Breast; Human Epidermal Growth Factor 2 Negative Carcinoma of Breast; Estrogen Receptor Positive Breast Cancer; Progesterone Receptor Positive Tumor; Metastatic Breast Cancer

  14. ENVIRONMENTAL FACTORS AFFECTING BREAST CANCER SUSCEPTIBILITY

    EPA Science Inventory

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

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

  15. Breast Cancer in the Personal Genomics Era

    PubMed Central

    Ellsworth, Rachel E.; Decewicz, David J.; Shriver, Craig D.; Ellsworth, Darrell L.

    2010-01-01

    Breast cancer is a heterogeneous disease with a complex etiology that develops from different cellular lineages, progresses along multiple molecular pathways, and demonstrates wide variability in response to treatment. The “standard of care” approach to breast cancer treatment in which all patients receive similar interventions is rapidly being replaced by personalized medicine, based on molecular characteristics of individual patients. Both inherited and somatic genomic variation is providing useful information for customizing treatment regimens for breast cancer to maximize efficacy and minimize adverse side effects. In this article, we review (1) hereditary breast cancer and current use of inherited susceptibility genes in patient management; (2) the potential of newly-identified breast cancer-susceptibility variants for improving risk assessment; (3) advantages and disadvantages of direct-to-consumer testing; (4) molecular characterization of sporadic breast cancer through immunohistochemistry and gene expression profiling and opportunities for personalized prognostics; and (5) pharmacogenomic influences on the effectiveness of current breast cancer treatments. Molecular genomics has the potential to revolutionize clinical practice and improve the lives of women with breast cancer. PMID:21037853

  16. THE LONG ISLAND BREAST CANCER STUDY (LIBCSP)

    EPA Science Inventory

    The NIEHS and the NCI are collaborating on the Long Island Breast Cancer Study Project (LIBCSP), which is designed to conduct epidemiologic research on the role of environmental factors in the etiology of breast cancer in women who live in Nassau and Suffolk counties, New York. T...

  17. Industrialization, electromagnetic fields, and breast cancer risk.

    PubMed Central

    Kheifets, L I; Matkin, C C

    1999-01-01

    The disparity between the rates of breast cancer in industrialized and less-industrialized regions has led to many hypotheses, including the theory that exposure to light-at-night and/or electromagnetic fields (EMF) may suppress melatonin and that reduced melatonin may increase the risk of breast cancer. In this comprehensive review we consider strengths and weaknesses of more than 35 residential and occupational epidemiologic studies that investigated the association between EMF and breast cancer. Although most of the epidemiologic data do not provide strong support for an association between EMF and breast cancer, because of the limited statistical power as well as the possibility of misclassification and bias present in much of the existing data, it is not possible to rule out a relationship between EMF and breast cancer. We make several specific recommendations for future studies carefully designed to test the melatonin-breast cancer and EMF-breast cancer hypotheses. Future study designs should have sufficient statistical power to detect small to moderate associations; include comprehensive exposure assessments that estimate residential and occupational exposures, including shift work; focus on a relevant time period; control for known breast cancer risks; and pay careful attention to menopausal and estrogen receptor status. PMID:10229714

  18. Depression in older breast cancer survivors

    PubMed Central

    2012-01-01

    Background Breast cancer is the most commonly diagnosed cancer among U.S. women .The 5-year survival rate for this tumour is nowadays 85%, and the 61% of these women are still alive at 15 years. When depression symptoms are present as a consequence of breast cancer treatments, they may interfere negatively with patients’ quality of life. The aim of this study was to examine the effects of breast cancer treatment on the quality of life and the impact of depression on the health-related life. Methods We enrolled 173 women aged 65-75 years with early stage breast cancer diagnosed over the last 10 years, initially recruited to participate in a study examining heath-related quality of life in the first 5 years after breast cancer diagnosis. Participants were divided into four groups: 1) 46 breast cancer survivors (aged 65-70); 2) 62 women diagnosed with breast cancer (aged 65-69); 3) 32 women with recurrent breast cancer after 10 years (aged 66-75); 4) 30 women in good health status (aged 60-70). The Geriatric Depression Scale was used as a routine part of a comprehensive geriatric assessment. Collection of data for the application of instruments, such as sociodemographic variables (age, educational level, social state) and clinical date (stage and time of the disease and treatment), was carried out by trained researcher assistants. Results Our results demonstrated the correlation between depression and previous cancer experiences. In fact, in patients with cancer experience, the grade of depression was significantly higher compared to healthy subjects. Furthermore, we demonstrated that the patients with recurrent breast cancer were severely depressed compared to other groups. Conclusions A high percentage of participants were identified as having emotional and/or well being problems. Further investigations on the cause of depression problems cancer-related are needed. PMID:23173836

  19. MiR-654-5p attenuates breast cancer progression by targeting EPSTI1

    PubMed Central

    Tan, Yu-Yan; Xu, Xiao-Yun; Wang, Jin-Feng; Zhang, Cheng-Wu; Zhang, Sheng-Chu

    2016-01-01

    MicroRNAs (miRNAs) dysregulation is a common event in a variety of human diseases including breast cancer. However, clinical relevance and biological role of miR-654-5p in the progression of breast cancer remain greatly elusive. Herein, the expression levels of miR-654-5p were aberrantly downregulated in human breast cancer specimens and four breast cancer cell lines. Low expression of miR-654-5p was strongly associated with advanced TNM stage and lymph node metastasis as well as a poor survival. Functional analysis showed that miR-654-5p overexpression inhibited cell growth and invasion, and induced cell apoptosis in two aggressive breast cancer cells. Further studies demonstrated that Epithelial stromal interaction 1 (EPSTI1) was a direct target gene of miR-654-5p and showed an inverse correlation with miR-654-5p expression. Forced expression of EPSTI1 could abrogate the inhibitory effect of miR-654-5p on the growth and invasion of breast cancer cells as well as apoptosis-induced ability. In conclusion, the present study highlights that miR-654-5p acts as a tumor suppressor in breast cancer through directly targeting EPSTI1, and their functional regulation may open a novel avenue with regard to the therapeutic target for breast cancer.

  20. Genome-wide association study identifies 25 known breast cancer susceptibility loci as risk factors for triple-negative breast cancer.

    PubMed

    Purrington, Kristen S; Slager, Susan; Eccles, Diana; Yannoukakos, Drakoulis; Fasching, Peter A; Miron, Penelope; Carpenter, Jane; Chang-Claude, Jenny; Martin, Nicholas G; Montgomery, Grant W; Kristensen, Vessela; Anton-Culver, Hoda; Goodfellow, Paul; Tapper, William J; Rafiq, Sajjad; Gerty, Susan M; Durcan, Lorraine; Konstantopoulou, Irene; Fostira, Florentia; Vratimos, Athanassios; Apostolou, Paraskevi; Konstanta, Irene; Kotoula, Vassiliki; Lakis, Sotiris; Dimopoulos, Meletios A; Skarlos, Dimosthenis; Pectasides, Dimitrios; Fountzilas, George; Beckmann, Matthias W; Hein, Alexander; Ruebner, Matthias; Ekici, Arif B; Hartmann, Arndt; Schulz-Wendtland, Ruediger; Renner, Stefan P; Janni, Wolfgang; Rack, Brigitte; Scholz, Christoph; Neugebauer, Julia; Andergassen, Ulrich; Lux, Michael P; Haeberle, Lothar; Clarke, Christine; Pathmanathan, Nirmala; Rudolph, Anja; Flesch-Janys, Dieter; Nickels, Stefan; Olson, Janet E; Ingle, James N; Olswold, Curtis; Slettedahl, Seth; Eckel-Passow, Jeanette E; Anderson, S Keith; Visscher, Daniel W; Cafourek, Victoria L; Sicotte, Hugues; Prodduturi, Naresh; Weiderpass, Elisabete; Bernstein, Leslie; Ziogas, Argyrios; Ivanovich, Jennifer; Giles, Graham G; Baglietto, Laura; Southey, Melissa; Kosma, Veli-Matti; Fischer, Hans-Peter; Reed, Malcom W R; Cross, Simon S; Deming-Halverson, Sandra; Shrubsole, Martha; Cai, Qiuyin; Shu, Xiao-Ou; Daly, Mary; Weaver, Joellen; Ross, Eric; Klemp, Jennifer; Sharma, Priyanka; Torres, Diana; Rüdiger, Thomas; Wölfing, Heidrun; Ulmer, Hans-Ulrich; Försti, Asta; Khoury, Thaer; Kumar, Shicha; Pilarski, Robert; Shapiro, Charles L; Greco, Dario; Heikkilä, Päivi; Aittomäki, Kristiina; Blomqvist, Carl; Irwanto, Astrid; Liu, Jianjun; Pankratz, Vernon Shane; Wang, Xianshu; Severi, Gianluca; Mannermaa, Arto; Easton, Douglas; Hall, Per; Brauch, Hiltrud; Cox, Angela; Zheng, Wei; Godwin, Andrew K; Hamann, Ute; Ambrosone, Christine; Toland, Amanda Ewart; Nevanlinna, Heli; Vachon, Celine M; Couch, Fergus J

    2014-05-01

    Triple-negative (TN) breast cancer is an aggressive subtype of breast cancer associated with a unique set of epidemiologic and genetic risk factors. We conducted a two-stage genome-wide association study of TN breast cancer (stage 1: 1529 TN cases, 3399 controls; stage 2: 2148 cases, 1309 controls) to identify loci that influence TN breast cancer risk. Variants in the 19p13.1 and PTHLH loci showed genome-wide significant associations (P < 5 × 10(-) (8)) in stage 1 and 2 combined. Results also suggested a substantial enrichment of significantly associated variants among the single nucleotide polymorphisms (SNPs) analyzed in stage 2. Variants from 25 of 74 known breast cancer susceptibility loci were also associated with risk of TN breast cancer (P < 0.05). Associations with TN breast cancer were confirmed for 10 loci (LGR6, MDM4, CASP8, 2q35, 2p24.1, TERT-rs10069690, ESR1, TOX3, 19p13.1, RALY), and we identified associations with TN breast cancer for 15 additional breast cancer loci (P < 0.05: PEX14, 2q24.1, 2q31.1, ADAM29, EBF1, TCF7L2, 11q13.1, 11q24.3, 12p13.1, PTHLH, NTN4, 12q24, BRCA2, RAD51L1-rs2588809, MKL1). Further, two SNPs independent of previously reported signals in ESR1 [rs12525163 odds ratio (OR) = 1.15, P = 4.9 × 10(-) (4)] and 19p13.1 (rs1864112 OR = 0.84, P = 1.8 × 10(-) (9)) were associated with TN breast cancer. A polygenic risk score (PRS) for TN breast cancer based on known breast cancer risk variants showed a 4-fold difference in risk between the highest and lowest PRS quintiles (OR = 4.03, 95% confidence interval 3.46-4.70, P = 4.8 × 10(-) (69)). This translates to an absolute risk for TN breast cancer ranging from 0.8% to 3.4%, suggesting that genetic variation may be used for TN breast cancer risk prediction. PMID:24325915

  1. Genome-wide association study identifies 25 known breast cancer susceptibility loci as risk factors for triple-negative breast cancer

    PubMed Central

    Couch, Fergus J.

    2014-01-01

    Triple-negative (TN) breast cancer is an aggressive subtype of breast cancer associated with a unique set of epidemiologic and genetic risk factors. We conducted a two-stage genome-wide association study of TN breast cancer (stage 1: 1529 TN cases, 3399 controls; stage 2: 2148 cases, 1309 controls) to identify loci that influence TN breast cancer risk. Variants in the 19p13.1 and PTHLH loci showed genome-wide significant associations (P < 5 × 10− 8) in stage 1 and 2 combined. Results also suggested a substantial enrichment of significantly associated variants among the single nucleotide polymorphisms (SNPs) analyzed in stage 2. Variants from 25 of 74 known breast cancer susceptibility loci were also associated with risk of TN breast cancer (P < 0.05). Associations with TN breast cancer were confirmed for 10 loci (LGR6, MDM4, CASP8, 2q35, 2p24.1, TERT-rs10069690, ESR1, TOX3, 19p13.1, RALY), and we identified associations with TN breast cancer for 15 additional breast cancer loci (P < 0.05: PEX14, 2q24.1, 2q31.1, ADAM29, EBF1, TCF7L2, 11q13.1, 11q24.3, 12p13.1, PTHLH, NTN4, 12q24, BRCA2, RAD51L1-rs2588809, MKL1). Further, two SNPs independent of previously reported signals in ESR1 [rs12525163 odds ratio (OR) = 1.15, P = 4.9 × 10− 4] and 19p13.1 (rs1864112 OR = 0.84, P = 1.8 × 10− 9) were associated with TN breast cancer. A polygenic risk score (PRS) for TN breast cancer based on known breast cancer risk variants showed a 4-fold difference in risk between the highest and lowest PRS quintiles (OR = 4.03, 95% confidence interval 3.46–4.70, P = 4.8 × 10− 69). This translates to an absolute risk for TN breast cancer ranging from 0.8% to 3.4%, suggesting that genetic variation may be used for TN breast cancer risk prediction. PMID:24325915

  2. The Changing World of Breast Cancer

    PubMed Central

    Kuhl, Christiane K.

    2015-01-01

    Abstract Compared with other fields of medicine, there is hardly an area that has seen such fast development as the world of breast cancer. Indeed, the way we treat breast cancer has changed fundamentally over the past decades. Breast imaging has always been an integral part of this change, and it undergoes constant adjustment to new ways of thinking. This relates not only to the technical tools we use for diagnosing breast cancer but also to the way diagnostic information is used to guide treatment. There is a constant change of concepts for and attitudes toward breast cancer, and a constant flux of new ideas, new treatment approaches, and new insights into the molecular and biological behavior of this disease. Clinical breast radiologists and even more so, clinician scientists, interested in breast imaging need to keep abreast with this rapidly changing world. Diagnostic or treatment approaches that are considered useful today may be abandoned tomorrow. Approaches that seem irrelevant or far too extravagant today may prove clinically useful and adequate next year. Radiologists must constantly question what they do, and align their clinical aims and research objectives with the changing needs of contemporary breast oncology. Moreover, knowledge about the past helps better understand present debates and controversies. Accordingly, in this article, we provide an overview on the evolution of breast imaging and breast cancer treatment, describe current areas of research, and offer an outlook regarding the years to come. PMID:26083829

  3. Breast thermography. A prognostic indicator for breast cancer survival.

    PubMed

    Isard, H J; Sweitzer, C J; Edelstein, G R

    1988-08-01

    A prognostic classification for thermographic staging of breast cancer has been applied to a cohort of 70 patients from 5040 screenees enrolled in the Albert Einstein Medical Center (AEMC) Breast Cancer Detection Demonstration Project (BCDDP). A diagnosis of breast cancer was established in each case before December 31, 1980. None of the patients have been lost to follow-up which extended from a minimum of 6 to a maximum of 13 years. Survival rates for those with favorable, equivocal, and poor thermographic factors are compared with each other and with results in accordance with tumor-node-metastasis (TNM) classification. As of December 31, 1986, there have been 22 (31.4%) deaths, all attributed to breast cancer. The thermographic scoring system clearly shows shorter survival for patients with poor thermographic prognostic factors, 30% surviving at 5 years and only 20% at 10 years compared with overall survival of 80% at 5 years and 70% at 10 years. PMID:3390789

  4. Human Epidermal Growth Factor Receptor Family-Targeted Therapies in the Treatment of HER2-Overexpressing Breast Cancer

    PubMed Central

    Eroglu, Zeynep; Tagawa, Tomoko

    2014-01-01

    Breast cancer characterized by overexpression of human epidermal growth factor receptor 2 (HER2) has been associated with more aggressive disease progression and a poorer prognosis. Although an improved understanding of breast cancer pathogenesis and the role of HER2 signaling has resulted in significant survival improvements in the past 20 years, resistance to HER2-targeted therapy remains a concern. A number of strategies to prevent or overcome resistance to HER2-targeted therapy in breast cancer are being evaluated. This article provides a comprehensive review of (a) the role of HER2 signaling in breast cancer pathogenesis, (b) potential receptor and downstream therapeutic targets in breast cancer to overcome resistance to HER2-targeted therapy, and (c) clinical trials evaluating agents targeting one or more members of the HER family and/or downstream pathways for the treatment of breast cancer, with a focus on metastatic disease. PMID:24436312

  5. Effect of Statins and Anticoagulants on Prostate Cancer Aggressiveness

    SciTech Connect

    Alizadeh, Moein; Sylvestre, Marie-Pierre; Zilli, Thomas; Van Nguyen, Thu; Guay, Jean-Pierre; Bahary, Jean-Paul; Taussky, Daniel

    2012-07-15

    Purpose: Statins and anticoagulants (ACs) have both been associated with a less-aggressive prostate cancer (PCa) and a better outcome after treatment of localized PCa. The results of these studies might have been confounded because patients might often take both medications. We examined their respective influence on PCa aggressiveness at initial diagnosis. Materials and Methods: We analyzed 381 patients treated with either external beam radiotherapy or brachytherapy for low-risk (n = 152), intermediate-risk (n = 142), or high-risk (n = 87) localized PCa. Univariate and multivariate logistic regression analyses were used to investigate an association between these drug classes and prostate cancer aggressiveness. We tested whether the concomitant use of statins and ACs had a different effect than that of either AC or statin use alone. Results: Of the 381 patients, 172 (45.1%) were taking statins and 141 (37.0%) ACs; 105 patients (27.6%) used both. On univariate analysis, the statin and AC users were associated with the prostate-specific antigen (PSA) level (p = .017) and National Comprehensive Cancer Network risk group (p = .0022). On multivariate analysis, statin use was associated with a PSA level <10 ng/mL (odds ratio, 2.9; 95% confidence interval, 1.3-6.8; p = .012) and a PSA level >20 ng/mL (odds ratio, 0.29; 95% confidence interval, 0.08-0.83; p = .03). The use of ACs was associated with a PSA level >20 ng/mL (odds ratio, 0.13; 95% confidence interval, 0.02-0.59, p = .02). Conclusion: Both AC and statins have an effect on PCa aggressiveness, with statins having a more stringent relationship with the PSA level, highlighting the importance of considering statin use in studies of PCa aggressiveness.

  6. Triple positive breast cancer: a distinct subtype?

    PubMed

    Vici, Patrizia; Pizzuti, Laura; Natoli, Clara; Gamucci, Teresa; Di Lauro, Luigi; Barba, Maddalena; Sergi, Domenico; Botti, Claudio; Michelotti, Andrea; Moscetti, Luca; Mariani, Luciano; Izzo, Fiorentino; D'Onofrio, Loretta; Sperduti, Isabella; Conti, Francesca; Rossi, Valentina; Cassano, Alessandra; Maugeri-Saccà, Marcello; Mottolese, Marcella; Marchetti, Paolo

    2015-02-01

    Breast cancer is a heterogeneous disease, and within the HER-2 positive subtype this is highly exemplified by the presence of substantial phenotypical and clinical heterogeneity, mostly related to hormonal receptor (HR) expression. It is well known how HER-2 positivity is commonly associated with a more aggressive tumor phenotype and decreased overall survival and, moreover, with a reduced benefit from endocrine treatment. Preclinical studies corroborate the role played by functional crosstalks between HER-2 and estrogen receptor (ER) signaling in endocrine resistance and, more recently, the activation of ER signaling is emerging as a possible mechanism of resistance to HER-2 blocking agents. Indeed, HER-2 positive breast cancer heterogeneity has been suggested to underlie the variability of response not only to endocrine treatments, but also to HER-2 blocking agents. Among HER-2 positive tumors, HR status probably defines two distinct subtypes, with dissimilar clinical behavior and different sensitivity to anticancer agents. The triple positive subtype, namely, ER/PgR/Her-2 positive tumors, could be considered the subset which most closely resembles the HER-2 negative/HR positive tumors, with substantial differences in biology and clinical outcome. We argue on whether in this subgroup the "standard" treatment may be considered, in selected cases, i.e., small tumors, low tumor burden, high expression of both hormonal receptors, an overtreatment. This article review the existing literature on biologic and clinical data concerning the HER-2/ER/PgR positive tumors, in an attempt to better define the HER-2 subtypes and to optimize the use of HER-2 targeted agents, chemotherapy and endocrine treatments in the various subsets. PMID:25554445

  7. Metastatic male ductal breast cancer mimicking obstructing primary colon cancer.

    PubMed

    Koleilat, Issam; Syal, Anil; Hena, Muhammad

    2010-03-01

    Male breast cancer comprises only about 1% of all breast cancers. Commonly, sites of metastases include the central nervous system, lungs, bones, and even liver. In females, extrahepatic gastrointestinal metastases are unusual but have been reported with various clinical presentations. We are reporting the first case of a male patient with a history of ductal breast carcinoma that developed colonic metastasis and presented with mechanical large bowel obstruction masquerading as primary colon cancer. PMID:23675178

  8. Metastatic Male Ductal Breast Cancer Mimicking Obstructing Primary Colon Cancer

    PubMed Central

    Koleilat, Issam; Syal, Anil; Hena, Muhammad

    2010-01-01

    Male breast cancer comprises only about 1% of all breast cancers. Commonly, sites of metastases include the central nervous system, lungs, bones, and even liver. In females, extrahepatic gastrointestinal metastases are unusual but have been reported with various clinical presentations. We are reporting the first case of a male patient with a history of ductal breast carcinoma that developed colonic metastasis and presented with mechanical large bowel obstruction masquerading as primary colon cancer. PMID:23675178

  9. SATB1 tethers multiple gene loci to reprogram expression profiledriving breast cancer metastasis

    SciTech Connect

    Han, Hye-Jung; Kohwi, Yoshinori; Kohwi-Shigematsu, Terumi

    2006-07-13

    Global changes in gene expression occur during tumor progression, as indicated by expression profiling of metastatic tumors. How this occurs is poorly understood. SATB1 functions as a genome organizer by folding chromatin via tethering multiple genomic loci and recruiting chromatin remodeling enzymes to regulate chromatin structure and expression of a large number of genes. Here we show that SATB1 is expressed at high levels in aggressive breast cancer cells, and is undetectable in non-malignant breast epithelial cells. Importantly, RNAi-mediated removal of SATB1 from highly-aggressive MDA-MB-231 cells altered the expression levels of over 1200 genes, restored breast-like acinar polarity in three-dimensional cultures, and prevented the metastastic phenotype in vivo. Conversely, overexpression of SATB1 in the less-aggressive breast cancer cell line Hs578T altered the gene expression profile and increased metastasis dramatically in vivo. Thus, SATB1 is a global regulator of gene expression in breast cancer cells, directly regulating crucial metastasis-associated genes, including ERRB2 (HER2/NEU), TGF-{beta}1, matrix metalloproteinase 3, and metastasin. The identification of SATB1 as a protein that re-programs chromatin organization and transcription profiles to promote breast cancer metastasis suggests a new model for metastasis and may provide means of therapeutic intervention.

  10. Breast cancer detection using time reversal

    NASA Astrophysics Data System (ADS)

    Sheikh Sajjadieh, Mohammad Hossein

    Breast cancer is the second leading cause of cancer death after lung cancer among women. Mammography and magnetic resonance imaging (MRI) have certain limitations in detecting breast cancer, especially during its early stage of development. A number of studies have shown that microwave breast cancer detection has potential to become a successful clinical complement to the conventional X-ray mammography. Microwave breast imaging is performed by illuminating the breast tissues with an electromagnetic waveform and recording its reflections (backscatters) emanating from variations in the normal breast tissues and tumour cells, if present, using an antenna array. These backscatters, referred to as the overall (tumour and clutter) response, are processed to estimate the tumour response, which is applied as input to array imaging algorithms used to estimate the location of the tumour. Due to changes in the breast profile over time, the commonly utilized background subtraction procedures used to estimate the target (tumour) response in array processing are impractical for breast cancer detection. The thesis proposes a new tumour estimation algorithm based on a combination of the data adaptive filter with the envelope detection filter (DAF/EDF), which collectively do not require a training step. After establishing the superiority of the DAF/EDF based approach, the thesis shows that the time reversal (TR) array imaging algorithms outperform their conventional conterparts in detecting and localizing tumour cells in breast tissues at SNRs ranging from 15 to 30dB.

  11. Breast Cancer Research at NASA

    NASA Technical Reports Server (NTRS)

    1998-01-01

    Epithelial cell monoculture: Long-term growth of human mammary epithelial cells (HMEC) grown in monoculture as 3-dimensional constructions in the presence of attachment beads in the NASA Bioreactor. A: A typical construct about 3.5 mm (less than 1/8th inch) in diameter with slightly dehydrted, crinkled beads contained on the surface as well as within the 3-dimensional structure. B: The center of these constructs is hollow. Crinkling of the beads causes a few to fall out, leaving crater-like impressiions in the construct. The central impression shows a small hole that accesses the hollow center of the construct. C: A closeup view of the cells and the hole the central impression. D: Closer views of cells in the construct showing sell-to-cell interactions. NASA's Marshall Space Flight Center (MSFC) is sponsoring research with Bioreactors, rotating wall vessels designed to grow tissue samples in space, to understand how breast cancer works. This ground-based work studies the growth and assembly of human mammary epithelial cell (HMEC) from breast cancer susceptible tissue. Radiation can make the cells cancerous, thus allowing better comparisons of healthy vs. tunorous tissue. Credit: Dr. Robert Richmond, NASA/Marshall Space Flight Center (MSFC).

  12. Depression in breast cancer patients.

    PubMed

    Cvetković, Jovana; Nenadović, Milutin

    2016-06-30

    Breast cancer is the third most common illness in the world and the most frequent malignant disease with women. Cytotoxic therapy is connected to significant psychiatric adverse effects, and the appearance of depressive symptoms is the most common. The main goal is determining the degree of depression with breast cancer patients in the oncology ward of the University Clinical Hospital in Niš and its connection to their marital status, age, level of education, economic status and the number of therapy cycles. This research is a prospective study. The statistical data analysis included measures of descriptive and analytical statistics. The presence of depressive symptoms of different intensity was showed in 76.00% of the interviewees in group I, and the second included 77.4%. The frequency distributions show that 27.084% interviewees from the first group showed signs of depressive symptoms, while the second included 25%. The intensity of these symptoms categorizes them into the group of moderate to significantly expressed depressive states, so they require therapeutic treatment. Depression is significantly more often recorded with cancer patients receiving cytotoxic therapy; mild depression is the most common, followed by moderate and severe depression. PMID:27138829

  13. KeraStat Skin Therapy in Treating Radiation Dermatitis in Patients With Newly Diagnosed Stage 0-IIIA Breast Cancer

    ClinicalTrials.gov

    2014-11-28

    Ductal Breast Carcinoma in Situ; Skin Reactions Secondary to Radiation Therapy; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer

  14. GDC-0941 and Cisplatin in Treating Patients With Androgen Receptor-Negative Triple Negative Metastatic Breast Cancer

    ClinicalTrials.gov

    2015-08-17

    Estrogen Receptor Negative Breast Cancer; Human Epidermal Growth Factor 2 Negative Carcinoma of Breast; Triple Negative Breast Cancer; Recurrent Breast Cancer; Stage IV Breast Cancer; Triple-negative Breast Cancer

  15. Trastuzumab Emtansine in Treating Older Patients With Human Epidermal Growth Factor Receptor 2-Positive Stage I-III Breast Cancer

    ClinicalTrials.gov

    2016-05-31

    Estrogen Receptor Negative; HER2 Positive Breast Carcinoma; Progesterone Receptor Negative; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Stage IIIC Breast Cancer

  16. [Infertility, fertility treatment and breast cancer risk].

    PubMed

    Riskin-Mashiah, Shlomit

    2013-10-01

    Breast cancer is the most common cancer in women in Israel and throughout the world. It is the leading cause of death from cancer in women. The cause of breast cancer is unknown; however gynecological history and hormonal factors have a major impact on the risk to develop breast cancer. Infertility affects 15-20% of couples in developed countries and most of them will need fertility treatment. The variety of fertility treatments and their use has been widespread during the last 50 years and especially since the introduction of in vitro fertilization. During fertility treatment, and depending on the type of treatment, there is ovarian hyperstimulation with maturation of several follicles and higher than normal estradiol levels. This article reviews the leading studies that evaluated the possible link between fertility treatment and the development of breast cancer. Most studies showed no association between fertility drugs and breast cancer. Whereas other researchers demonstrated a possible link between some fertility drugs and increased risk for breast cancer in certain subgroups. Therefore, larger studies with longer follow-up periods and better control for all possible confounding factors are needed in order to confirm the safety of fertility treatments in the long run. The combination of infertility and fertility treatment might cause harm, such as an increased risk for breast cancer Therefore, one has to consider carefully, together with the woman, the need for fertility treatment and give the lowest possible dosage for the shortest duration in order to minimize the risk. PMID:24450034

  17. DDT Exposure in Utero and Breast Cancer

    PubMed Central

    La Merrill, Michele; Krigbaum, Nickilou Y.; Yeh, Gregory; Park, June-Soo; Zimmermann, Lauren; Cirillo, Piera M.

    2015-01-01

    Context: Currently no direct evidence links in utero dichlorodiphenyltrichloroethane (DDT) exposure to human breast cancer. However, in utero exposure to another xenoestrogen, diethylstilbestrol, predicts an increased breast cancer risk. If this finding extends to DDT, it could have far-reaching consequences. Many women were heavily exposed in utero during widespread DDT use in the 1960s. They are now reaching the age of heightened breast cancer risk. DDT exposure persists and use continues in Africa and Asia without clear knowledge of the consequences for the next generation. Hypothesis: In utero exposure to DDT is associated with an increased risk of breast cancer. Design: This was a case-control study nested in a prospective 54-year follow-up of 9300 daughters in the Child Health and Development Studies pregnancy cohort (n = 118 breast cancer cases, diagnosed by age 52 y and 354 controls matched on birth year). Setting and Participants: Kaiser Foundation Health Plan members who received obstetric care in Alameda County, California, from 1959 to 1967, and their adult daughters participated in the study. Main Outcome Measure: Daughters' breast cancer diagnosed by age 52 years as of 2012 was measured. Results: Maternal o,p′-DDT predicted daughters' breast cancer (odds ratio fourth quartile vs first = 3.7, 95% confidence interval 1.5–9.0). Mothers' lipids, weight, race, age, and breast cancer history did not explain the findings. Conclusions: This prospective human study links measured DDT exposure in utero to risk of breast cancer. Experimental studies are essential to confirm results and discover causal mechanisms. Findings support classification of DDT as an endocrine disruptor, a predictor of breast cancer, and a marker of high risk. PMID:26079774

  18. Curcumin enhances poly(ADP-ribose) polymerase inhibitor sensitivity to chemotherapy in breast cancer cells.

    PubMed

    Choi, Young Eun; Park, Eunmi

    2015-12-01

    Poly(ADP-ribose) polymerase (PARP) inhibitor has shown promising responses in homologous recombination (HR) repair-deficient cancer cells. More specifically, targeting HR pathway in combination with PARP inhibitor has been an effective chemotherapy strategy by so far. Curcumin has been recognized as anticancer agents for several types of cancers. Here, we demonstrate that curcumin inhibits a critical step in HR pathway, Rad51 foci formation, and accumulates γ-H2AX levels in MDA-MB-231 breast cancer cells. Curcumin also directly reduces HR and induces cell death with cotreatment of PARP inhibitor in MDA-MB-231 breast cancer cells. Moreover, curcumin, when combined with ABT-888, could effectively delayed breast tumor formation in vivo. Our study indicates that cotreatment of curcumin and PARP inhibitor might be useful for the combination chemotherapy for aggressive breast cancer treatment as a natural bioactive compound. PMID:26350251

  19. Inhibitors of hypoxia-inducible factor 1 block breast cancer metastatic niche formation and lung metastasis.

    PubMed

    Wong, Carmen Chak-Lui; Zhang, Huafeng; Gilkes, Daniele M; Chen, Jasper; Wei, Hong; Chaturvedi, Pallavi; Hubbi, Maimon E; Semenza, Gregg L

    2012-07-01

    Intratumoral hypoxia, a frequent finding in metastatic cancer, results in the activation of hypoxia-inducible factors (HIFs). HIFs are implicated in many steps of breast cancer metastasis, including metastatic niche formation through increased expression of lysyl oxidase (LOX) and lysyl oxidase-like (LOXL) proteins, enzymes that remodel collagen at the metastatic site and recruit bone marrow-derived cells (BMDCs) to the metastatic niche. We investigated the effect of two chemically and mechanistically distinct HIF inhibitors, digoxin and acriflavine, on breast cancer metastatic niche formation. Both drugs blocked the hypoxia-induced expression of LOX and LOXL proteins, collagen cross-linking, CD11b⁺ BMDC recruitment, and lung metastasis in an orthotopic breast cancer model. Patients with HIF-1 α-overexpressing breast cancers are at increased risk of metastasis and mortality and our results suggest that such patients may benefit from aggressive therapy that includes a HIF inhibitor. PMID:22231744

  20. Estrogen sulfotransferases in breast and endometrial cancers.

    PubMed

    Pasqualini, Jorge Raul

    2009-02-01

    Estrogen sulfotransferase is significantly more active in the normal breast cell (e.g., Human 7) than in the cancer cell (e.g., MCF-7). The data suggest that in breast cancer sulfoconjugated activity is carried out by another enzyme, the SULT1A, which acts at high concentration of the substrates. In breast cancer cells sulfotransferase (SULT) activity can be stimulated by various progestins: medrogestone, promegestone, and nomegestrol acetate, as well as by tibolone and its metabolites. SULT activities can also be controlled by other substances including phytoestrogens, celecoxib, flavonoids (e.g., quercetin, resveratrol), and isoflavones. SULT expression was localized in breast cancer cells, which can be stimulated by promegestone and correlated with the increase of the enzyme activity. The estrogen sulfotransferase (SULT1E1), which acts at nanomolar concentration of estradiol, can inactivate most of this hormone present in the normal breast; however, in the breast cancer cells, the sulfotransferase denoted as SULT1A1 is mainly present, and this acts at micromolar concentrations of E(2). A correlation was postulated among breast cancer cell proliferation, the effect of various progestins, and sulfotransferase stimulation. In conclusion, it is suggested that factors involved in the stimulation of the estrogen sulfotransferases could provide new possibilities for the treatment of patients with hormone-dependent breast and endometrial cancers. PMID:19250196

  1. Combination Drug Delivery Approaches in Metastatic Breast Cancer

    PubMed Central

    Lee, Jun H.; Nan, Anjan

    2012-01-01

    Disseminated metastatic breast cancer needs aggressive treatment due to its reduced response to anticancer treatment and hence low survival and quality of life. Although in theory a combination drug therapy has advantages over single-agent therapy, no appreciable survival enhancement is generally reported whereas increased toxicity is frequently seen in combination treatment especially in chemotherapy. Currently used combination treatments in metastatic breast cancer will be discussed with their challenges leading to the introduction of novel combination anticancer drug delivery systems that aim to overcome these challenges. Widely studied drug delivery systems such as liposomes, dendrimers, polymeric nanoparticles, and water-soluble polymers can concurrently carry multiple anticancer drugs in one platform. These carriers can provide improved target specificity achieved by passive and/or active targeting mechanisms. PMID:22619725

  2. Breast Cancer Screening and Prevention.

    PubMed

    Nattinger, Ann B; Mitchell, Julie L

    2016-06-01

    This issue provides a clinical overview of breast cancer screening and prevention, focusing on risk assessment, screening, prevention, and practice improvement. The content of In the Clinic is drawn from the clinical information and education resources of the American College of Physicians (ACP), including MKSAP (Medical Knowledge and Self-Assessment Program). Annals of Internal Medicine editors develop In the Clinic in collaboration with the ACP's Medical Education and Publishing divisions and with the assistance of additional science writers and physician writers. PMID:27270661

  3. Review of ultrasound appearance in inflammatory breast cancer: A pictorial essay.

    PubMed

    Abeywardhana, Dilupani Y; Nascimento, Vinicius C; Dissanayake, Deepthi; Taylor, Donna; Metcalf, Cecily; Saunders, Christobel; Wylie, Elizabeth

    2016-02-01

    Inflammatory breast cancer (IBC) is a rare malignancy accounting for 1-2% of breast cancers. It has an aggressive clinical presentation and poor prognosis. The sonographic findings in 41 patients with a clinical diagnosis of IBC and biopsy-proven breast malignancy are presented in this study. The most common finding was the presence of skin thickening (92%). Multiple small anechoic spaces within the dermis, correlating with the presence of dermal lymphatic invasion by tumour emboli on histopathology were noted in approximately one-third of cases. Other sonographic findings included single or multiple masses, parenchymal oedema, axillary lymphadenopathy, echogenic foci consistent with microcalcifications and increased vascularity. PMID:26631841

  4. Antipsychotic treatment in breast cancer patients.

    PubMed

    Rahman, Tahir; Clevenger, Charles V; Kaklamani, Virginia; Lauriello, John; Campbell, Austin; Malwitz, Kari; Kirkland, Robert S

    2014-06-01

    Special consideration is required when prescribing antipsychotic drugs for patients with an existing diagnosis of breast cancer. The package inserts of all approved antipsychotics contain precautions regarding their administration in this patient group. These drugs are well known to elevate serum prolactin levels to varying degrees. Overexpression of the prolactin receptor is seen in more than 95% of human breast cancers. Many genes that are activated by the prolactin receptor are associated with tumorigenesis and cancer cell proliferation. The authors discuss the pathophysiology, clinical implications, and pertinent preclinical data and make specific recommendations regarding the use of antipsychotics in patients with breast cancer. PMID:24880509

  5. Genomic similarities between breast and ovarian cancers

    Cancer.gov

    One subtype of breast cancer shares many genetic features with high-grade serous ovarian cancer, a cancer that is very difficult to treat, according to researchers supported by the National Institutes of Health. The findings suggest that the two cancers a

  6. CHST11 gene expression and DNA methylation in breast cancer

    PubMed Central

    HERMAN, DAMIR; LEAKEY, TATIANA I.; BEHRENS, ALICE; YAO-BORENGASSER, AIWEI; COONEY, CRAIG A.; JOUSHEGHANY, FARIBA; PHANAVANH, BOUNLEUT; SIEGEL, ERIC R.; SAFAR, A. MAZIN; KOROURIAN, SOHEILA; KIEBER-EMMONS, THOMAS; MONZAVI-KARBASSI, BEHJATOLAH

    2015-01-01

    Our previously published data link P-selectin-reactive chondroitin sulfate structures on the surface of breast cancer cells to metastatic behavior of cells. We have shown that a particular sulfation pattern mediated by the expression of carbohydrate (chondroitin 4) sulfotransferase-11 (CHST11) correlates with P-selectin binding and aggressiveness of human breast cancer cell lines. The present study was performed to evaluate the prognostic value of CHST11 expression and determine whether aberrant DNA methylation controls CHST11 expression in breast cancer. Publicly available datasets were used to examine the association of CHST11 expression to aggressiveness and progression of breast cancer. Methylation status was analyzed using bisulfite genomic sequencing. 5-aza-2′-deoxycytidine (5AzadC) was used for DNA demethylation. Reduced representation bisulfite sequencing was performed in the CpG island of CHST11 with a minimum coverage of 10. Quantitative real-time RT-PCR was employed to confirm the expression profile of CHST11 in breast cancer cell lines. Flow cytometry was also used to confirm the expression of the CHST11 product, chondroitin sulfate A (CS-A). The expression of CHST11 was significantly higher in basal-like and Her2-amplified cell lines compared to luminal cell lines. CHST11 was also highly expressed in cancer tissues compared to normal tissues and the expression levels were significantly associated with tumor progression. We observed very low levels of DNA methylation in a CpG island of CHST11 in basal-like cells but very high levels in the same region in luminal cells. Treatment of MCF7 cells, a luminal cell line with very low expression of CHST11, with 5AzadC increased the expression of CHST11 and its immediate product, CS-A, in a dose-dependent manner. These results suggest that CHST11 may play a direct role in progression of breast cancer and that its expression is controlled by DNA methylation. Therefore, in addition to CHST11 mRNA levels, the

  7. Expression of alpha-GalNAc glycoproteins by breast cancers.

    PubMed Central

    Brooks, S. A.; Leathem, A. J.

    1995-01-01

    The expression of complex carbohydrates recognised by Helix pomatia lectin (HPA, nominal monosaccharide binding specificity alpha-GalNAc) has been shown to predict unfavourable prognosis in breast and other cancers. It has been suggested that the prognostic significance of HPA binding may be through recognition of either Tn epitope (alpha-GalNAc-O-serine/threonine) or blood group A antigen (terminal alpha-1-->3GalNAc attached to the basic H-antigen, Fuc-alpha-1-->2-Gal-beta-1-->4(or 3) GlcNAc-->R). In this study, the expression of glycoproteins terminating in alpha-GalNAc residues was investigated immunohistochemically using HPA and two monoclonal antibodies--BRIC 66 (anti-alpha-GalNAc) and BRIC 111 (anti-Tn). In paraffin sections, 74/87 (85%) of breast cancers expressed HPA-binding ligands, while 28/87 (32%) were positive for BRIC 66 binding and 25/87 (29%) expressed Tn. Distribution of staining patterns were distinctive and different with the three markers. BRIC 66, BRIC 111 and HPA binding to glycoproteins derived from breast cancer homogenates and to blood group A and Tn positive glycoproteins in Western blots confirmed the immunohistochemistry data. The results suggest that the prognostic significance of HPA binding in breast cancer is unlikely to be simply through recognition of blood group A antigen or Tn epitope on cancer cells. Breast cancers may express a complex profile of related but distinct glycans sharing similar terminal immunodominant sugar GalNAc, which may be implicated in aggressive biological behaviour. Images Figure 1 Figure 2 PMID:7537516

  8. Questionnaires in Identifying Upper Extremity Function and Quality of Life After Treatment in Patients With Breast Cancer

    ClinicalTrials.gov

    2015-10-24

    Musculoskeletal Complication; Recurrent Breast Carcinoma; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer; Therapy-Related Toxicity

  9. Time-resolved fluorescence for breast cancer detection using an octreotate-indocyanine green derivative dye conjugate

    NASA Astrophysics Data System (ADS)

    Sordillo, Laura A.; Das, B. B.; Pu, Yang; Liang, Kexian; Milione, Giovanni; Sordillo, Peter P.; Achilefu, Sam; Alfano, R. R.

    2013-03-01

    Time-resolved fluorescence was used to investigate malignant and normal adjacent breast tissues stained with a conjugate of indocyanine green and octreotate. A marked increase in fluorescence lifetime intensity was seen in the breast cancer sample compared to the normal sample. The fluorescent lifetimes were also investigated and showed similar fluorescence decay curves in stained malignant and normal breast tissue. These results confirm that somatostatin receptors occur on human breast carcinomas, suggest that the presence of somatostatin receptors should be investigated as a marker of breast cancer aggressiveness, and suggest that this conjugate might be used to detect the presence of residual breast cancer after surgery, allowing better assessment of tumor margins and reducing the need for second or repeat biopsies in selected patients. These results may also provide clues for designing future treatment options for breast cancer patients.

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

    SciTech Connect

    Chu, Tian-Li; Zhao, Hong-Meng; Li, Yue; Chen, Ao-Xiang; Sun, Xuan; Ge, Jie

    2014-04-04

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

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

    PubMed Central

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

    2015-01-01

    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. PMID:26487968

  12. The history of breast cancer advocacy.

    PubMed

    Braun, Susan

    2003-01-01

    There have been four key steps in the advent of breast cancer advocacy: priming the market, engaging consumers, establishing political advocacy, and taking the advocacy mainstream. Breast cancer was surrounded by secrecy until the 1980s, when brave individuals such as former First Ladies Betty Ford and Nancy Reagan, and founder of the Susan G. Komen Foundation, Nancy Brinker (Susan Komen's sister), began speaking publicly about the personal impact of the disease, which increased awareness of breast cancer and made it more acceptable to talk about it openly. At the same time, statistics about breast cancer were presented in new ways that the public could understand. Public health advocates played a key role in the second step, engaging consumers, when they established guidelines in the 1980s that encouraged women to perform breast self-examinations (BSEs) and have screening mammograms and clinical breast examinations (CBEs). Other events that helped engage consumers were increased media coverage of breast cancer issues, the founding of the Komen Race for the Cure in 1983, and the establishment of other programs that both educated the public and raised funds. Funds from these efforts enabled advocates to hold educational forums and produce educational materials in different media and tailored to different audiences and to become active in the funding of research. The third step, political action, became possible when breast cancer advocates joined together in the 1980s and 1990s to work toward legislative, regulatory, and funding changes, such as passage of the Mammography Quality Standards Act and increased funding for the National Cancer Institute. These efforts contributed to a more than quadrupling of federal funding for breast cancer research in the 1990s. Going mainstream, the final step in the advocacy process, entailed establishing a solid base of support to ensure that the message about breast cancer stays strong and fresh. This has been achieved by engaging

  13. Main controversies in breast cancer

    PubMed Central

    Zervoudis, Stephane; Iatrakis, George; Tomara, Eirini; Bothou, Anastasia; Papadopoulos, George; Tsakiris, George

    2014-01-01

    In this article, we have reviewed available evidence for diagnosis, treatment, and follow-up in female breast cancer (BC). Into daily clinical practice some controversies are occurred. Especially, in the diagnosis field, despite the fact that the optimal age in which screening mammography should start is a subject of intense controversy, there is a shift toward the beginning at the age of 40 although it is suggested that the net benefit is small for women aged 40 to 49 years. In addition, a promising tool in BC screening seems to be breast tomosynthesis. Other tools such as 3D ultrasound and shear wave elastography (SWE) are full of optimism in BC screening although ultrasonography is not yet a first-line screening method and there is insufficient evidence to recommend the systemic use of the SWE for BC screening. As for breast magnetic resonance imaging (MRI), even if it is useful in BC detection in women who have a strong family history of BC, it is not generally recommended as a screening tool. Moreover, based on the lack of randomized clinical trials showing a benefit of presurgical breast MRI in overall survival, it’s integration into breast surgical operations remains debatable. Interestingly, in contrast to fine needle aspiration, core biopsy has gained popularity in presurgical diagnosis. Furthermore, after conservative surgery in patients with positive sentinel lymph nodes, the recent tendency is the shift from axillary dissection to axillary conserving strategies. While the accuracy of sentinel lymph node after neoadjuvant chemotherapy and second BC surgery remains controversial, more time is needed for evaluation and for determining the optimal interval between the two surgeries. Additionally, in the decision between immediate or delayed breast reconstruction, there is a tendency in the immediate use. In the prevention of BC, the controversial issue between tamoxifen and raloxifene becomes clear with raloxifene be more profitable through the toxicities

  14. Molecular basis of invasion in breast cancer.

    PubMed

    McSherry, E A; Donatello, S; Hopkins, A M; McDonnell, S

    2007-12-01

    Cancer cell invasion involves the breaching of tissue barriers by cancer cells, and the subsequent infiltration of these cells throughout the surrounding tissue. In breast cancer, invasion at the molecular level requires the coordinated efforts of numerous processes within the cancer cell and its surroundings. Accumulation of genetic changes which impair the regulation of cell growth and death is generally accepted to initiate cancer. Loss of cell-adhesion molecules, resulting in a loss in tissue architecture, in parallel with matrix remodelling may also confer a motile or migratory advantage to breast cancer cells. The tumour microenvironment may further influence the behaviour of these cancer cells through expression of cytokines, growth factors, and proteases promoting chemotaxis and invasion. This review will attempt to summarise recent work on these fundamental processes influencing or facilitating breast cancer cell invasion. (Part of a Multi-author Review). PMID:17957337

  15. Epithelial-Mesenchymal Transition and Breast Cancer.

    PubMed

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

    2016-01-01

    Breast cancer is the most common cancer in women and distant site metastasis is the main cause of death in breast cancer patients. There is increasing evidence supporting the role of epithelial-mesenchymal transition (EMT) in tumor cell progression, invasion, and metastasis. During the process of EMT, epithelial cancer cells acquire molecular alternations that facilitate the loss of epithelial features and gain of mesenchymal phenotype. Such transformation promotes cancer cell migration and invasion. Moreover, emerging evidence suggests that EMT is associated with the increased enrichment of cancer stem-like cells (CSCs) and these CSCs display mesenchymal characteristics that are resistant to chemotherapy and target therapy. However, the clinical relevance of EMT in human cancer is still under debate. This review will provide an overview of current evidence of EMT from studies using clinical human breast cancer tissues and its associated challenges. PMID:26821054

  16. Epithelial-Mesenchymal Transition and Breast Cancer

    PubMed Central

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

    2016-01-01

    Breast cancer is the most common cancer in women and distant site metastasis is the main cause of death in breast cancer patients. There is increasing evidence supporting the role of epithelial-mesenchymal transition (EMT) in tumor cell progression, invasion, and metastasis. During the process of EMT, epithelial cancer cells acquire molecular alternations that facilitate the loss of epithelial features and gain of mesenchymal phenotype. Such transformation promotes cancer cell migration and invasion. Moreover, emerging evidence suggests that EMT is associated with the increased enrichment of cancer stem-like cells (CSCs) and these CSCs display mesenchymal characteristics that are resistant to chemotherapy and target therapy. However, the clinical relevance of EMT in human cancer is still under debate. This review will provide an overview of current evidence of EMT from studies using clinical human breast cancer tissues and its associated challenges. PMID:26821054

  17. Contrast enhanced ultrasound of breast cancer

    PubMed Central

    Cassano, E; Rizzo, S; Bozzini, A; Menna, S; Bellomi, M

    2006-01-01

    The importance of ultrasound examination in the diagnosis of breast cancer has been widely demonstrated. During the last few years, the introduction of ultrasound contrast media has been considered a promising tool for studying the vascular pattern of focal lesions within the breast. Our purpose was to assess whether contrast-enhanced (CE) ultrasound examination, performed using specific contrast imaging modes, can be helpful for detection and characterization of breast lesions, and for prediction of the response of breast cancer to therapy. PMID:16478698

  18. Contrast enhanced ultrasound of breast cancer.

    PubMed

    Cassano, E; Rizzo, S; Bozzini, A; Menna, S; Bellomi, M

    2006-01-01

    The importance of ultrasound examination in the diagnosis of breast cancer has been widely demonstrated. During the last few years, the introduction of ultrasound contrast media has been considered a promising tool for studying the vascular pattern of focal lesions within the breast. Our purpose was to assess whether contrast-enhanced (CE) ultrasound examination, performed using specific contrast imaging modes, can be helpful for detection and characterization of breast lesions, and for prediction of the response of breast cancer to therapy. PMID:16478698

  19. Eribulin mesylate in breast cancer.

    PubMed

    Verdaguer, Helena; Morilla, Idoia; Urruticoechea, Ander

    2013-11-01

    Eribulin mesylate is a synthetic analog of halichondrin B (a polyether macrolide isolated from a marine sponge). It is a nontaxane microtubule dynamics inhibitor with a novel mechanism of action. It is the first drug that has demonstrated an improvement in overall survival as a single agent compared with the physician's choice of currently available treatments in locally advanced or metastatic breast cancer, previously treated with anthracyclines and taxanes. It has shown a good manageable tolerability profile. This drug has been approved by the US FDA and by the EMA for patients with locally advanced or metastatic breast cancer who have received at least two chemotherapeutic regimens for advanced/metastatic disease. Prior therapy should have included an anthracycline and a taxane in either the adjuvant or metastatic setting unless patients were not suitable for these treatments. The aim of this article is to describe the mechanism of action, pharmacokinetics, pharmacodynamics and the most relevant clinical trials in the development of this drug. PMID:24161305

  20. Characterization of a naturally occurring breast cancer subset enriched in EMT and stem cell characteristics

    SciTech Connect

    Hennessy, Bryan T.; Gonzalez-Angulo, Ana-Maria; Stemke-Hale, Katherine; Gilcrease, Michael Z.; Krishnamurthy, Savitri; Lee, Ju-Seog; Fridlyand, Jane; Sahin, Aysegul; Agarwal, Roshan; Joy, Corwin; Liu, Wenbin; Stivers, David; Baggerly, Keith; Carey, Mark; Lluch, Ana; Monteagudo, Carlos; He, Xiaping; Weigman, Victor; Fan, Cheng; Palazzo, Juan; Hortobagyi, Gabriel N.; Nolden, Laura K.; Wang, Nicholas J.; Valero, Vicente; Gray, Joe W.; Perou, Charles M.; Mills, Gordon B.

    2009-05-19

    Metaplastic breast cancers (MBC) are aggressive, chemoresistant tumors characterized by lineage plasticity. To advance understanding of their pathogenesis and relatedness to other breast cancer subtypes, 28 MBCs were compared with common breast cancers using comparative genomic hybridization, transcriptional profiling, and reverse-phase protein arrays and by sequencing for common breast cancer mutations. MBCs showed unique DNA copy number aberrations compared with common breast cancers. PIK3CA mutations were detected in 9 of 19 MBCs (47.4%) versus 80 of 232 hormone receptor-positive cancers (34.5%; P = 0.32), 17 of 75 HER-2-positive samples (22.7%; P = 0.04), 20 of 240 basal-like cancers (8.3%; P < 0.0001), and 0 of 14 claudin-low tumors (P = 0.004). Of 7 phosphatidylinositol 3-kinase/AKT pathway phosphorylation sites, 6 were more highly phosphorylated in MBCs than in other breast tumor subtypes. The majority of MBCs displayed mRNA profiles different from those of the most common, including basal-like cancers. By transcriptional profiling, MBCs and the recently identified claudin-low breast cancer subset constitute related receptor-negative subgroups characterized by low expression of GATA3-regulated genes and of genes responsible for cell-cell adhesion with enrichment for markers linked to stem cell function and epithelial-to-mesenchymal transition (EMT). In contrast to other breast cancers, claudin-low tumors and most MBCs showed a significant similarity to a 'tumorigenic' signature defined using CD44{sup +}/CD24{sup -} breast tumor-initiating stem cell-like cells. MBCs and claudin-low tumors are thus enriched in EMT and stem cell-like features, and may arise from an earlier, more chemoresistant breast epithelial precursor than basal-like or luminal cancers. PIK3CA mutations, EMT, and stem cell-like characteristics likely contribute to the poor outcomes of MBC and suggest novel therapeutic targets.

  1. Anaplastic lymphoma kinase is expressed in different subtypes of human breast cancer

    SciTech Connect

    Perez-Pinera, Pablo; Chang, Y.; Astudillo, A.; Mortimer, J.; Deuel, T.F. . E-mail: tfdeuel@scripps.edu

    2007-06-29

    Pleiotrophin (PTN, Ptn) is an 18 kDa cytokine expressed in human breast cancers. Since inappropriate expression of Ptn stimulates progression of breast cancer in transgenic mice and a dominant negative PTN reverses the transformed phenotype of human breast cancer cells that inappropriately express Ptn, it is suggested that constitutive PTN signaling in breast cancer cells that inappropriately express Ptn activates pathways that promote a more aggressive breast cancer phenotype. Pleiotrophin signals by inactivating its receptor, the receptor protein tyrosine phosphatase (RPTP){beta}/{zeta}, and, recently, PTN was found to activate anaplastic lymphoma kinase (ALK) through the PTN/RPTP{beta}/{zeta} signaling pathway in PTN-stimulated cells, not through a direct interaction of PTN with ALK and thus not through the PTN-enforced dimerization of ALK. Since full-length ALK is activated in different malignant cancers and activated ALK is a potent oncogenic protein, we examined human breast cancers to test the possibility that ALK may be expressed in breast cancers and potentially activated through the PTN/RPTP{beta}/{zeta} signaling pathway; we now demonstrate that ALK is strongly expressed in different histological subtypes of human breast cancer; furthermore, ALK is expressed in both nuclei and cytoplasm and, in the 'dotted' pattern characteristic of ALK fusion proteins in anaplastic large cell lymphoma. This study thus supports the possibility that activated ALK may be important in human breast cancers and potentially activated either through the PTN/RPTP{beta}/{zeta} signaling pathway, or, alternatively, as an activated fusion protein to stimulate progression of breast cancer in humans.

  2. Addition of vasopressin synthetic analogue [V(4)Q(5)]dDAVP to standard chemotherapy enhances tumour growth inhibition and impairs metastatic spread in aggressive breast tumour models.

    PubMed

    Garona, Juan; Pifano, Marina; Pastrian, Maria B; Gomez, Daniel E; Ripoll, Giselle V; Alonso, Daniel F

    2016-08-01

    [V(4)Q(5)]dDAVP is a novel 2nd generation vasopressin analogue with robust antitumour activity against metastatic breast cancer. We recently reported that, by acting on vasopressin V2r membrane receptor present in tumour cells and microvascular endothelium, [V(4)Q(5)]dDAVP inhibits angiogenesis and metastatic progression of the disease without overt toxicity. Despite chemotherapy remaining as a primary therapeutic option for aggressive breast cancer, its use is limited by low selectivity and associated adverse effects. In this regard, we evaluated potential combinational benefits by adding [V(4)Q(5)]dDAVP to standard-of-care chemotherapy. In vitro, combination of [V(4)Q(5)]dDAVP with sub-IC50 concentrations of paclitaxel or carmustine resulted in a cooperative inhibition of breast cancer cell growth in comparison to single-agent therapy. In vivo antitumour efficacy of [V(4)Q(5)]dDAVP addition to chemotherapy was first evaluated using the triple-negative MDA-MB-231 breast cancer xenograft model. Tumour-bearing mice were treated with i.v. injections of [V(4)Q(5)]dDAVP (0.3 μg/kg, thrice weekly) in combination with weekly cycles of paclitaxel (10 mg/kg i.p.). After 6 weeks of treatment, combination regimen resulted in greater tumour growth inhibition compared to monotherapy. [V(4)Q(5)]dDAVP addition was also associated with reduction of local aggressiveness, and impairment of tumour invasion and infiltration of the skin. Benefits of combined therapy were confirmed in the hormone-independent and metastatic F3II breast cancer model by combining [V(4)Q(5)]dDAVP with carmustine (25 mg/kg i.p.). Interestingly, [V(4)Q(5)]dDAVP plus cytotoxic agents severely impaired colony forming ability of tumour cells and inhibited breast cancer metastasis to lung. The present study shows that [V(4)Q(5)]dDAVP may complement conventional chemotherapy by modulating metastatic progression and early stages of microtumour establishment, and thus supports further preclinical testing of

  3. Social determinants of Black-White disparities in breast cancer mortality: a review.

    PubMed

    Gerend, Mary A; Pai, Manacy

    2008-11-01

    Despite the recent decline in breast cancer mortality, African American women continue to die from breast cancer at higher rates than do White women. Beyond the fact that breast cancer tends to be a more biologically aggressive disease in African American than in White women, this disparity in breast cancer mortality also reflects social barriers that disproportionately affect African American women. These barriers hinder cancer prevention and control efforts and modify the biological expression of disease. The present review focuses on delineating social, economic, and cultural factors that are potentially responsible for Black-White disparities in breast cancer mortality. This review was guided by the social determinants of health disparities model, a model that identifies barriers associated with poverty, culture, and social injustice as major causes of health disparities. These barriers, in concert with genetic, biological, and environmental factors, can promote differential outcomes for African American and White women along the entire breast cancer continuum, from screening and early detection to treatment and survival. Barriers related to poverty include lack of a primary care physician, inadequate health insurance, and poor access to health care. Barriers related to culture include perceived invulnerability, folk beliefs, and a general mistrust of the health care system. Barriers related to social injustice include racial profiling and discrimination. Many of these barriers are potentially modifiable. Thus, in addition to biomedical advancements, future efforts to reduce disparities in breast cancer mortality should address social barriers that perpetuate disparities among African American and White women in the United States. PMID:18990731

  4. Friend leukemia virus integration 1 activates the Rho GTPase pathway and is associated with metastasis in breast cancer.

    PubMed

    Song, Wei; Li, Wei; Li, Lingyu; Zhang, Shilin; Yan, Xu; Wen, Xue; Zhang, Xiaoying; Tian, Huimin; Li, Ailing; Hu, Ji-Fan; Cui, Jiuwei

    2015-09-15

    Breast cancer is the most prevalent malignant disease in women worldwide. In patients with breast cancer, metastasis to distant sites directly determines the survival outcome. However, the molecular mechanism underlying metastasis in breast cancer remains to be defined. In this report, we found that Friend leukemia virus integration 1 (FLI1) proto-oncogene was differentially expressed between the aggressive MDA-MB231 and the non-aggressive MCF-7 breast cancer cells. Congruently, immunohistochemical staining of clinical samples revealed that FLI1 was overexpressed in breast cancers as compared with the adjacent tissues. The abundance of FLI1 protein was strongly correlated with the advanced stage, poor differentiation, and lymph node metastasis in breast cancer patients. Knockdown of FLI1 with small interfering RNAs significantly attenuated the potential of migration and invasion in highly metastatic human breast cancer cells. FLI1 oncoprotein activated the Rho GTPase pathway that is known to play a role in tumor metastasis. This study for the first time identifies FLI1 as a clinically and functionally important target gene of metastasis, providing a rationale for developing FLI1 inhibitors in the treatment of breast cancer. PMID:26156017

  5. RAD51B in Familial Breast Cancer

    PubMed Central

    Pelttari, Liisa M.; Khan, Sofia; Vuorela, Mikko; Kiiski, Johanna I.; Vilske, Sara; Nevanlinna, Viivi; Ranta, Salla; Schleutker, Johanna; Winqvist, Robert; Kallioniemi, Anne; Dörk, Thilo; Bogdanova, Natalia V.; Figueroa, Jonine; Pharoah, Paul D. P.; Schmidt, Marjanka K.; Dunning, Alison M.; García-Closas, Montserrat; Bolla, Manjeet K.; Dennis, Joe; Michailidou, Kyriaki; Wang, Qin; Hopper, John L.; Southey, Melissa C.; Rosenberg, Efraim H.; Fasching, Peter A.; Beckmann, Matthias W.; Peto, Julian; dos-Santos-Silva, Isabel; Sawyer, Elinor J.; Tomlinson, Ian; Burwinkel, Barbara; Surowy, Harald; Guénel, Pascal; Truong, Thérèse; Bojesen, Stig E.; Nordestgaard, Børge G.; Benitez, Javier; González-Neira, Anna; Neuhausen, Susan L.; Anton-Culver, Hoda; Brenner, Hermann; Arndt, Volker; Meindl, Alfons; Schmutzler, Rita K.; Brauch, Hiltrud; Brüning, Thomas; Lindblom, Annika; Margolin, Sara; Mannermaa, Arto; Hartikainen, Jaana M.; Chenevix-Trench, Georgia; Van Dyck, Laurien; Janssen, Hilde; Chang-Claude, Jenny; Rudolph, Anja; Radice, Paolo; Peterlongo, Paolo; Hallberg, Emily; Olson, Janet E.; Giles, Graham G.; Milne, Roger L.; Haiman, Christopher A.; Schumacher, Fredrick; Simard, Jacques; Dumont, Martine; Kristensen, Vessela; Borresen-Dale, Anne-Lise; Zheng, Wei; Beeghly-Fadiel, Alicia; Grip, Mervi; Andrulis, Irene L.; Glendon, Gord; Devilee, Peter; Seynaeve, Caroline; Hooning, Maartje J.; Collée, Margriet; Cox, Angela; Cross, Simon S.; Shah, Mitul; Luben, Robert N.; Hamann, Ute; Torres, Diana; Jakubowska, Anna; Lubinski, Jan; Couch, Fergus J.; Yannoukakos, Drakoulis; Orr, Nick; Swerdlow, Anthony; Darabi, Hatef; Li, Jingmei; Czene, Kamila; Hall, Per; Easton, Douglas F.; Mattson, Johanna; Blomqvist, Carl; Aittomäki, Kristiina; Nevanlinna, Heli

    2016-01-01

    Common variation on 14q24.1, close to RAD51B, has been associated with breast cancer: rs999737 and rs2588809 with the risk of female breast cancer and rs1314913 with the risk of male breast cancer. The aim of this study was to investigate the role of RAD51B variants in breast cancer predisposition, particularly in the context of familial breast cancer in Finland. We sequenced the coding region of RAD51B in 168 Finnish breast cancer patients from the Helsinki region for identification of possible recurrent founder mutations. In addition, we studied the known rs999737, rs2588809, and rs1314913 SNPs and RAD51B haplotypes in 44,791 breast cancer cases and 43,583 controls from 40 studies participating in the Breast Cancer Association Consortium (BCAC) that were genotyped on a custom chip (iCOGS). We identified one putatively pathogenic missense mutation c.541C>T among the Finnish cancer patients and subsequently genotyped the mutation in additional breast cancer cases (n = 5259) and population controls (n = 3586) from Finland and Belarus. No significant association with breast cancer risk was seen in the meta-analysis of the Finnish datasets or in the large BCAC dataset. The association with previously identified risk variants rs999737, rs2588809, and rs1314913 was replicated among all breast cancer cases and also among familial cases in the BCAC dataset. The most significant association was observed for the haplotype carrying the risk-alleles of all the three SNPs both among all cases (odds ratio (OR): 1.15, 95% confidence interval (CI): 1.11–1.19, P = 8.88 x 10−16) and among familial cases (OR: 1.24, 95% CI: 1.16–1.32, P = 6.19 x 10−11), compared to the haplotype with the respective protective alleles. Our results suggest that loss-of-function mutations in RAD51B are rare, but common variation at the RAD51B region is significantly associated with familial breast cancer risk. PMID:27149063

  6. RAD51B in Familial Breast Cancer.

    PubMed

    Pelttari, Liisa M; Khan, Sofia; Vuorela, Mikko; Kiiski, Johanna I; Vilske, Sara; Nevanlinna, Viivi; Ranta, Salla; Schleutker, Johanna; Winqvist, Robert; Kallioniemi, Anne; Dörk, Thilo; Bogdanova, Natalia V; Figueroa, Jonine; Pharoah, Paul D P; Schmidt, Marjanka K; Dunning, Alison M; García-Closas, Montserrat; Bolla, Manjeet K; Dennis, Joe; Michailidou, Kyriaki; Wang, Qin; Hopper, John L; Southey, Melissa C; Rosenberg, Efraim H; Fasching, Peter A; Beckmann, Matthias W; Peto, Julian; Dos-Santos-Silva, Isabel; Sawyer, Elinor J; Tomlinson, Ian; Burwinkel, Barbara; Surowy, Harald; Guénel, Pascal; Truong, Thérèse; Bojesen, Stig E; Nordestgaard, Børge G; Benitez, Javier; González-Neira, Anna; Neuhausen, Susan L; Anton-Culver, Hoda; Brenner, Hermann; Arndt, Volker; Meindl, Alfons; Schmutzler, Rita K; Brauch, Hiltrud; Brüning, Thomas; Lindblom, Annika; Margolin, Sara; Mannermaa, Arto; Hartikainen, Jaana M; Chenevix-Trench, Georgia; Van Dyck, Laurien; Janssen, Hilde; Chang-Claude, Jenny; Rudolph, Anja; Radice, Paolo; Peterlongo, Paolo; Hallberg, Emily; Olson, Janet E; Giles, Graham G; Milne, Roger L; Haiman, Christopher A; Schumacher, Fredrick; Simard, Jacques; Dumont, Martine; Kristensen, Vessela; Borresen-Dale, Anne-Lise; Zheng, Wei; Beeghly-Fadiel, Alicia; Grip, Mervi; Andrulis, Irene L; Glendon, Gord; Devilee, Peter; Seynaeve, Caroline; Hooning, Maartje J; Collée, Margriet; Cox, Angela; Cross, Simon S; Shah, Mitul; Luben, Robert N; Hamann, Ute; Torres, Diana; Jakubowska, Anna; Lubinski, Jan; Couch, Fergus J; Yannoukakos, Drakoulis; Orr, Nick; Swerdlow, Anthony; Darabi, Hatef; Li, Jingmei; Czene, Kamila; Hall, Per; Easton, Douglas F; Mattson, Johanna; Blomqvist, Carl; Aittomäki, Kristiina; Nevanlinna, Heli

    2016-01-01

    Common variation on 14q24.1, close to RAD51B, has been associated with breast cancer: rs999737 and rs2588809 with the risk of female breast cancer and rs1314913 with the risk of male breast cancer. The aim of this study was to investigate the role of RAD51B variants in breast cancer predisposition, particularly in the context of familial breast cancer in Finland. We sequenced the coding region of RAD51B in 168 Finnish breast cancer patients from the Helsinki region for identification of possible recurrent founder mutations. In addition, we studied the known rs999737, rs2588809, and rs1314913 SNPs and RAD51B haplotypes in 44,791 breast cancer cases and 43,583 controls from 40 studies participating in the Breast Cancer Association Consortium (BCAC) that were genotyped on a custom chip (iCOGS). We identified one putatively pathogenic missense mutation c.541C>T among the Finnish cancer patients and subsequently genotyped the mutation in additional breast cancer cases (n = 5259) and population controls (n = 3586) from Finland and Belarus. No significant association with breast cancer risk was seen in the meta-analysis of the Finnish datasets or in the large BCAC dataset. The association with previously identified risk variants rs999737, rs2588809, and rs1314913 was replicated among all breast cancer cases and also among familial cases in the BCAC dataset. The most significant association was observed for the haplotype carrying the risk-alleles of all the three SNPs both among all cases (odds ratio (OR): 1.15, 95% confidence interval (CI): 1.11-1.19, P = 8.88 x 10-16) and among familial cases (OR: 1.24, 95% CI: 1.16-1.32, P = 6.19 x 10-11), compared to the haplotype with the respective protective alleles. Our results suggest that loss-of-function mutations in RAD51B are rare, but common variation at the RAD51B region is significantly associated with familial breast cancer risk. PMID:27149063

  7. Chemotherapy With or Without Trastuzumab After Surgery in Treating Women With Invasive Breast Cancer

    ClinicalTrials.gov

    2016-09-15

    Estrogen Receptor Negative; Estrogen Receptor Positive; HER2/Neu Positive; Progesterone Receptor Negative; Progesterone Receptor Positive; Recurrent Breast Carcinoma; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Stage IIIC Breast Cancer

  8. Cyr61 promotes breast tumorigenesis and cancer progression

    SciTech Connect

    Tsai, Miaw-Sheue; Bogart, Daphne F.; Castaneda, Jessica M.; Li, Patricia; Lupu, Ruth

    2002-01-16

    Cyr61, a member of the CCN family of genes, is an angiogenic factor. We have shown that it is overexpressed in invasive and metastatic human breast cancer cells and tissues. Here, we investigated whether Cyr61 is necessary and/or sufficient to bypass the ''normal'' estrogen (E2) requirements for breast cancer cell growth. Our results demonstrate that under E2-depleted condition, Cyr61 is sufficient to induce MCF-7 cells grow in the absence of E2. MCF-7 cells transfected with Cyr61 (MCF-7/Cyr61) became E2-independent but still E2-responsive. On the other hand, MCF-7/vector cells remain E2-dependent. MCF-7/Cyr61 cells acquire an antiestrogen-resistant phenotype, one of the most common clinical occurrences during breast cancer progression. MCF-7/Cyr61 cells are anchorage-independent and capable of forming Matrigel outgrowth patterns in the absence of E2. ERa expression in MCF-7/Cyr61 cells is decreased although still functional. Additionally, MCF-7/Cyr61 cells are tumorigenic in ovariectomized athymic nude mice. The tumors resemble human invasive carcinomas with increased vascularization and overexpression of vascular endothelial growth factor (VEGF). Our results demonstrate that Cyr61 is a tumor-promoting factor and a key regulator of breast cancer progression. This study provides evidence that Cyr61 is sufficient to induce E2-independence and anti-E2 resistance, and to promote invasiveness in vitro, and to induce tumorigenesis in vivo, all of which are characteristics of an aggressive breast cancer phenotype.

  9. Epidemiology of basal-like breast cancer

    PubMed Central

    Millikan, Robert C.; Newman, Beth; Tse, Chiu-Kit; Moorman, Patricia G.; Conway, Kathleen; Smith, Lisa V.; Labbok, Miriam H.; Geradts, Joseph; Bensen, Jeannette T.; Jackson, Susan; Nyante, Sarah; Livasy, Chad; Carey, Lisa; Earp, H. Shelton; Perou, Charles M.

    2008-01-01

    Risk factors for the newly identified “intrinsic” breast cancer subtypes (luminal A, luminal B, basal-like and human epidermal growth factor receptor 2-positive/estrogen receptor-negative) were determined in the Carolina Breast Cancer Study, a population-based, case–control study of African-American and white women. Immunohistochemical markers were used to subtype 1,424 cases of invasive and in situ breast cancer, and case subtypes were compared to 2,022 controls. Luminal A, the most common subtype, exhibited risk factors typically reported for breast cancer in previous studies, including inverse associations for increased parity and younger age at first full-term pregnancy. Basal-like cases exhibited several associations that were opposite to those observed for luminal A, including increased risk for parity and younger age at first term full-term pregnancy. Longer duration breastfeeding, increasing number of children breastfed, and increasing number of months breastfeeding per child were each associated with reduced risk of basal-like breast cancer, but not luminal A. Women with multiple live births who did not breastfeed and women who used medications to suppress lactation were at increased risk of basal-like, but not luminal A, breast cancer. Elevated waist-hip ratio was associated with increased risk of luminal A in postmenopausal women, and increased risk of basal-like breast cancer in pre- and postmenopausal women. The prevalence of basal-like breast cancer was highest among premenopausal African-American women, who also showed the highest prevalence of basal-like risk factors. Among younger African-American women, we estimate that up to 68% of basal-like breast cancer could be prevented by promoting breastfeeding and reducing abdominal adiposity. PMID:17578664

  10. High histologic grade and increased relative content of tryptophan in breast cancer using ratios from fingerprint fluorescence spectral peaks

    NASA Astrophysics Data System (ADS)

    Sordillo, Laura A.; Sordillo, Peter P.; Budansky, Yury; Pu, Yang; Alfano, R. R.

    2015-03-01

    Histologic grade is a very important, but underappreciated, parameter of breast cancer aggressiveness. Despite its importance, it has historically not been included as one of the criteria for staging of this cancer. In this study, spectral fluorescence profiles from patients with breast carcinoma were acquired. Ratios of emission peaks at 340 over 440,460 nm from biomolecules in malignant and normal samples were calculated. Cancerous over normal ratios (double ratio (DR) method) were evaluated with respect to tumor characteristics. Increased tryptophan content in breast cancer tissues correlates strongly with high grade, but not with lymph node metastases, estrogen receptor, progesterone receptor or Her-2-Neu receptor status.

  11. Cell Fate Decisions During Breast Cancer Development

    PubMed Central

    Gross, Kayla; Wronski, Ania; Skibinski, Adam; Phillips, Sarah; Kuperwasser, Charlotte

    2016-01-01

    During the formation of breast cancer, many genes become altered as cells evolve progressively from normal to a pre-malignant to a malignant state of growth. How mutations in genes lead to specific subtypes of human breast cancer is only partially understood. Here we review how initial genetic or epigenetic alterations within mammary epithelial cells (MECs) can alter cell fate decisions and put pre-malignant cells on a path towards cancer development with specific phenotypes. Understanding the early stages of breast cancer initiation and progression and how normal developmental processes are hijacked during transformation has significant implications for improving early detection and prevention of breast cancer. In addition, insights gleaned from this understanding may also be important for developing subtype-specific treatment options. PMID:27110512

  12. RECQL: a new breast cancer susceptibility gene

    PubMed Central

    Banerjee, Taraswi; Brosh, Robert M

    2015-01-01

    Identifying and characterizing novel genetic risk factors for BRCA1/2 negative breast cancers is highly relevant for early diagnosis and development of a management plan. Mutations in a number of DNA repair genes have been associated with genomic instability and development of breast and various other cancers. Whole exome sequencing efforts by 2 groups have led to the discovery in distinct populations of multiple breast cancer susceptibility mutations in RECQL, a gene that encodes a DNA helicase involved in homologous recombination repair and response to replication stress. RECQL pathogenic mutations were identified that truncated or disrupted the RECQL protein or introduced missense mutations in its helicase domain. RECQL mutations may serve as a useful biomarker for breast cancer. Targeting RECQL associated tumors with novel DNA repair inhibitors may provide a new strategy for anti-cancer therapy. PMID:26125302

  13. Breast Cancer Basics and You | NIH MedlinePlus the Magazine

    MedlinePlus

    ... page please turn JavaScript on. Feature: Screening For Breast Cancer Breast Cancer Basics and You Past Issues / Summer 2014 ... women, although male breast cancer is rare. The Breasts Inside a woman's breast are 15 to 20 ...

  14. Breast Cancer Basics and You: Introduction | NIH MedlinePlus the Magazine

    MedlinePlus

    ... of this page please turn Javascript on. Feature: Breast Cancer Breast Cancer Basics and You: Introduction Past Issues / Spring - ... women, although male breast cancer is rare. The Breasts Inside a woman's breast are 15 to 20 ...

  15. Screening and self examination for breast cancer.

    PubMed Central

    Austoker, J.

    1994-01-01

    Breast cancer is the major form of cancer in women, with nearly 30,000 new cases and over 15,000 deaths in the United Kingdom each year. Breast screening by mammography has been shown in randomised trials to reduce mortality from breast cancer in women aged 50 and over. An NHS breast screening programme has been in operation in the United Kingdom since 1988. Its aim is to reduce mortality from breast cancer by 25% in the population of women invited to be screened. The uptake of mammography among the eligible population may be the single most important determinant if the programme is to be effective. Primary care teams have an important part to play in encouraging women to attend for screening and in providing information, advice, and reassurance at all stages of the screening process. To date, routine breast self examination has not been shown to be an effective method of screening for breast cancer and should not therefore be promoted as a primary screening procedure. There is, however, a case to be made for women to become more "breast aware." PMID:8044097

  16. Preventing aggressive prostate cancer with proven cardiovascular disease preventive methods.

    PubMed

    Moyad, Mark A

    2015-01-01

    Cardiovascular disease (CVD) has been the number one cause of death in the U.S. for 114 of the last 115 years. Risk factors for prostate cancer have primarily mirrored risk proven risk factors for CVD, especially aggressive disease. Obesity, dyslipidemia, glucose intolerance, metabolic syndrome, unhealthy dietary habits or caloric excess, lack of physical activity, and inflammation are just some of these shared risk factors. The evidence also suggests proven CVD preventive measures are identical to prostate cancer preventive measures, especially in regard to aggressive disease. Thus, apart from lifestyle measures that can encourage optimal heart and prostate health there are potentially several dietary supplements that need to be avoided in healthy men because they may also increase the risk of prostate cancer. However, there are also several low-cost, generic, safe in the appropriate individuals, and naturally derived agents that could reduce prostate cancer risk, and these can be discussed and remembered utilizing the acronym S.A.M. (statins, aspirin, and/or metformin). PMID:26112486

  17. β-Blockers Reduce Breast Cancer Recurrence and Breast Cancer Death: A Meta-Analysis.

    PubMed

    Childers, W Kurtis; Hollenbeak, Christopher S; Cheriyath, Pramil

    2015-12-01

    The normal physiologic stress mechanism, mediated by the sympathetic nervous system, causes a release of the neurotransmitters epinephrine and norepinephrine. Preclinical data have demonstrated an effect on tumor progression and metastasis via the sympathetic nervous system mediated primarily through the β-adrenergic receptor (β-AR) pathway. In vitro data have shown an increase in tumor growth, migration, tumor angiogenesis, and metastatic spread in breast cancer through activation of the β-AR. Retrospective cohort studies on the clinical outcomes of β-blockers in breast cancer outcomes showed no clear consensus. The purpose of this study was to perform a systematic review and meta-analysis of the effect of β-blockers on breast cancer outcomes. A systematic review was performed using the Cochrane library and PubMed. Publications between the dates of January 2010 and December 2013 were identified. Available hazard ratios (HRs) were extracted for breast cancer recurrence, breast cancer death, and all-cause mortality and pooled using a random effects meta-analysis. A total of 7 studies contained results for at least 1 of the outcomes of breast cancer recurrence, breast cancer death, or all-cause mortality in breast cancer patients receiving β-blockers. In the 5 studies that contained results for breast cancer recurrence, there was no statistically significant risk reduction (HR, 0.67; 95% confidence interval [CI], 0.39-1.13). Breast cancer death results were contained in 4 studies, which also suggested a significant reduction in risk (HR, 0.50; 95% CI, 0.32-0.80). Among the 4 studies that reported all-cause mortality, there was no significant effect of β-blockers on risk (HR, 1.02; 95% CI, 0.75-1.37). Results of this systematic review and meta-analysis suggest that the use of β-blockers significantly reduced risk of breast cancer death among women with breast cancer. PMID:26516037

  18. Using breast cancer cell CXCR4 surface expression to predict liposome binding and cytotoxicity.

    PubMed

    Guo, Peng; You, Jin-Oh; Yang, Jiang; Moses, Marsha A; Auguste, Debra T

    2012-11-01

    The primary cause of mortality in breast cancer is tumor aggressiveness, characterized by metastases to regional lymph nodes, bone marrow, lung, and liver. C-X-C chemokine receptor type 4 (CXCR4) has been shown to mobilize breast cancer cells along chemokine gradients. Quantification of CXCR4 surface expression may predict the efficacy of anti-CXCR4 labeled liposomal therapeutics to target and kill breast cancer cells. We evaluated gene and surface receptor expression of CXCR4 on breast cancer cell lines distinguished as having low and high invasiveness, MDA-MB-175VII and HCC1500, respectively. CXCR4 surface expression did not correlate with invasiveness. MDA-MB-175VII exhibited more binding to anti-CXCR4 labeled liposomes relative to HCC1500. Increased binding correlated with greater cell death relative to IgG labeled liposomes. Quantitative cell characterization may be used to select targeted therapeutics with enhanced efficacy and minimal side effects. PMID:22884683

  19. Prognostic Value of Cancer Stem Cells Markers in Triple-Negative Breast Cancer

    PubMed Central

    Collina, Francesca; Di Bonito, Maurizio; Li Bergolis, Valeria; De Laurentiis, Michelino; Vitagliano, Carlo; Cerrone, Margherita; Nuzzo, Francesco; Cantile, Monica; Botti, Gerardo

    2015-01-01

    Triple-negative breast cancer (TNBC) has a significant clinical relevance of being associated with a shorter median time to relapse and death and does not respond to endocrine therapy or other available targeted agents. Increased aggressiveness of this tumor, as well as resistance to standard drug therapies, may be associated with the presence of stem cell populations within the tumor. Several stemness markers have been described for the various histological subtypes of breast cancer, such as CD44, CD24, CD133, ALDH1, and ABCG2. The role of these markers in breast cancer is not clear yet and above all there are conflicting opinions about their real prognostic value. To investigate the role of CSCs markers in TNBC cancerogenesis and tumor progression, we selected 160 TNBCs samples on which we detected protein expression of CD44, CD24, CD133, ALDH1, and ABCG2 by immunohistochemistry. Our results highlighted a real prognostic role only for CD44 in TNBCs. All other CSCs markers do not appear to be related to the survival of TNBC patients. In conclusion, despite the fact that the presence of the cancer stem cells in the tumor provides important information on its potential aggressiveness, today their detection by immunohistochemistry is not sufficient to confirm their role in carcinogenesis, because specific markers probably are not yet identified. PMID:26504780

  20. [Adjuvant drug therapies for breast cancer].

    PubMed

    Huovinen, Riikka; Auvinen, Päivi; Mattson, Johanna; Joensuu, Heikki

    2015-01-01

    Most breast cancers are hormone receptor positive and exhibit a slow growth pattern. Based on biological properties, breast cancers are divided into four different biological subtypes. Furthermore, these subtypes are indicative of the risk of recurrence, which is also influenced by the size of the tumor and extension to lymph nodes. Postoperative adjuvant drug therapy is chosen on the basis of the biological type. Chemotherapy can be used in all subtypes. Hormonal therapies are used exclusively for the treatment of hormone receptor positive breast cancer. Trastuzumab antibody belongs to the treatment of the HER2 positive subtype. PMID:26245052

  1. [Screening for cervical and breast cancer].

    PubMed

    Wilm, J; Schüler-Toprak, S; Ortmann, O

    2016-09-01

    Screening programs for cervical cancer and breast cancer lead to a clear reduction of mortality. Starting in 2018 screening for cervical cancer will be structured as an organized program as already exists for breast cancer. In future screening for cervical cancer will be primarily performed by human papillomavirus (HPV) testing at intervals of 5 years while cytological examination (Pap smear) will also be available as an additional or alternative procedure. For breast cancer screening in Germany an annual clinical examination with palpation and mammography screening at 2‑year intervals is provided for women aged between 50 and 69 years. In Germany only approximately 50 % of invited women have used the opportunity to participate in screening in recent years. Weighing the benefits against the harms of cancer screening programs is always important in the process of evaluation of different strategies. PMID:27577734

  2. Fertility preservation for breast cancer patients.

    PubMed

    Oktem, Ozgur; Oktay, Kutluk

    2009-11-01

    Breast cancer is the most common neoplasm in women and accounts for 26% (182,460) of all new cancer cases among women. With the use of screening mammography and advancement in other diagnostic modalities, many cases of breast cancer now can be diagnosed and treated at early stages of the disease. Unfortunately, adjuvant chemotherapy regimens commonly used in the treatment of breast cancer may cause premature ovarian failure due to their cytotoxic effects on the germ cells in the ovary. Therefore preservation of fertility in breast cancer survivors at reproductive age has become an important quality of life issue. Fertility preservation is a recently emerged field of reproductive medicine that may help protect the reproductive capability of the cancer survivors and allow them to have children in the future. Embryo freezing is the most established fertility preservation strategy. But conventional ovarian stimulation protocols are contraindicated in breast cancer patients because of the rise of estrogen and its metabolites to supraphysiological levels. Recently developed ovarian stimulation protocols with aromatase inhibitor letrozole and tamoxifen appear to provide a safe stimulation with endogenous estrogen levels comparable with those achieved in the natural cycle. Oocyte freezing can be considered in single women and in those who do not wish donor sperm. Ovarian tissue freezing could also be an option in breast cancer patients who do not wish or have a time for an in vitro fertilization cycle, which requires 10 to 14 days of ovarian stimulation. PMID:19806518

  3. Older women, breast cancer, and social support

    PubMed Central

    Levine, Ellen G.; Aviv, Caryn; Ewing, Cheryl; Au, Alfred

    2009-01-01

    Introduction One in ten women over the age of 65 will develop breast cancer. Despite this high incidence of breast cancer among older women, social support for them is often inadequate. This paper describes a qualitative study of the impact of a breast cancer diagnosis on older women from racially/ethnically diverse populations and their subsequent need for social support. Methods Forty-seven older African American, Asian American, Caucasian and Latina women between the ages of 65 to 83 participated in a larger study examining the impact of breast cancer on women from racially/ethnically diverse populations and the meaning and nature of social support. The women completed an in-depth qualitative interview on the psychosocial impact of breast cancer and the meaning and nature of social support. Results and Conclusion The results indicate that there are variations in reactions to a breast cancer diagnosis among older women, and that these reactions impact their experiences with seeking social support at diagnosis and during treatment. Respondents were concerned about their aging bodies, potential dependency on others, and loss of autonomy. At the same time, the severity of cancer treatment and existing co-morbidities often meant they needed to learn to receive support, and to reach out if they had no support. The implications of these findings underscore the older cancer patient’s need to strengthen her supportive networks at the time of diagnosis, during treatment, and post-treatment. PMID:20967554

  4. Metabolic profiling of breast cancer: Differences in central metabolism between subtypes of breast cancer cell lines.

    PubMed

    Willmann, Lucas; Schlimpert, Manuel; Halbach, Sebastian; Erbes, Thalia; Stickeler, Elmar; Kammerer, Bernd

    2015-09-01

    Although the concept of aerobic glycolysis in cancer was already reported in the 1930s by Otto Warburg, the understanding of metabolic pathways remains challenging especially due to the heterogeneity of cancer. In consideration of four different time points (1, 2, 4, and 7 days of incubation), GC-MS profiling of metabolites was performed on cell extracts and supernatants of breast cancer cell lines (MDA-MB-231, -453, BT-474) with different sub classification and the breast epithelial cell line MCF-10A. To the exclusion of trypsinization, direct methanolic extraction, cell scraping and cell disruption was executed to obtain central metabolites. Major differences in biochemical pathways have been observed in the breast cancer cell lines compared to the breast epithelial cell line, as well as between the breast cancer cell lines themselves. Characteristics of breast cancer subtypes could be correlated to their individual metabolic profiles. PLS-DA revealed the discrimination of breast cancer cell lines from MCF-10A based on elevated amino acid levels. The observed metabolic signatures have great potential as biomarker for breast cancer as well as an improved understanding of subtype specific phenomenons of breast cancer. PMID:26218769

  5. Kallikrein gene downregulation in breast cancer.

    PubMed

    Yousef, G M; Yacoub, G M; Polymeris, M-E; Popalis, C; Soosaipillai, A; Diamandis, E P

    2004-01-12

    Recent evidence suggests that many members of the human kallikrein gene family are differentially regulated in breast cancer and other endocrine-related malignancies. In this study, we utilised the serial analysis of gene expression (SAGE) and expressed sequence tag (EST) databases of the Cancer Genome Anatomy Project (CGAP) to perform in silico analyses of the expression pattern of the 15 human kallikrein genes in normal and cancerous breast tissues and cell lines using different analytical tools such as Virtual Northern blotting, Digital Differential Display and X-profiler. Our results indicate that at least four kallikrein genes (KLK5, 6, 8, 10) are downregulated in breast cancer. Probing eight normal and 24 breast cancer SAGE libraries with gene-specific tags for each of the above kallikreins indicated moderate-to-high expression densities in normal breast (27-319 tags per million; tpm, in two to five out of eight libraries), compared to no or low expression (0 - 34 tpm in zero to two libraries out of 24) in breast cancer. These data were verified by screening the EST databases, where all mRNA clones isolated for these genes, except for one in each, were from normal breast libraries, with no clones detected from breast cancer tissues or cell lines (with the exception of KLK8). X-profiler comparison of two pools of normal and breast cancer libraries further verified the presence of significant downregulation of expression levels of 4 of the kallikreins genes (KLK5, 6, 10, 12). We experimentally verified the downregulation of these four kallikreins (KLK5, 6, 8, 10 and 12) by RT - PCR analysis. PMID:14710225

  6. Gamma-secretase/Notch Signalling Pathway Inhibitor RO4929097 in Treating Patients With Advanced, Metastatic, or Recurrent Triple Negative Invasive Breast Cancer

    ClinicalTrials.gov

    2016-07-19

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

  7. Assessment of Breast Cancer Risk and Belief in Breast Cancer Screening Among the Primary Healthcare Nurses.

    PubMed

    İz, Fatma Başalan; Tümer, Adile

    2016-09-01

    Breast cancer is the most frequently diagnosed cancer in women. Early detection of breast cancer is known to increase survival rates significantly after diagnosis. This research was carried out to determine the level of breast cancer risk among primary healthcare nurses and their belief in breast cancer screening. In this descriptive research, the data were collected in face-to-face interviews with the participants. The researchers contacted all primary healthcare nurses currently working in the province. The data collection tools included a questionnaire form on sociodemographic characteristics, breast cancer risk assessment form, and Champion's Health Belief Model Scale (CHBMS) for breast cancer screening. In data analysis, descriptive statistics, t test, and analysis of variance (ANOVA) were used. The mean age of nurses was 35 ± 3.6. The mean score for the breast cancer risk assessment form was calculated as 82.9 ± 18.7. The subscale scores for the CHBMS for breast cancer screening were as follows: susceptibility 7.3 ± 1.8, seriousness 19.5 ± 4.1, benefits of breast self-exam 15.5 ± 2.6, barriers to breast self-exam 15.1 ± 2.8, self-efficacy 40.3 ± 7.0, and motivation 19.5 ± 4.1. The risk of breast cancer was found to be low in the study group. The analysis of the subscale scores for the CHBMS for breast cancer screening revealed that nurses had a below-average susceptibility perception, a somewhat lower perception of seriousness, an above-average mean score for perceived benefits, a moderate barrier perception, a relatively high perceived self-efficacy, and motivation above average. PMID:26758047

  8. Tripartite motif containing 28 (TRIM28) promotes breast cancer metastasis by stabilizing TWIST1 protein.

    PubMed

    Wei, Chunli; Cheng, Jingliang; Zhou, Boxv; Zhu, Li; Khan, Md Asaduzzaman; He, Tao; Zhou, Sufang; He, Jian; Lu, Xiaoling; Chen, Hanchun; Zhang, Dianzheng; Zhao, Yongxiang; Fu, Junjiang

    2016-01-01

    TRIM28 regulates its target genes at both transcriptional and posttranscriptional levels. Here we report that a TRIM28-TWIST1-EMT axis exists in breast cancer cells and TRIM28 promotes breast cancer metastasis by stabilizing TWIST1 and subsequently enhancing EMT. We find that TRIM28 is highly expressed in both cancer cell lines and advanced breast cancer tissues, and the levels of TRIM28 and TWIST1 are positively correlated with the aggressiveness of breast carcinomas. Overexpression and depletion of TRIM28 up- and down-regulates the protein, but not the mRNA levels of TWIST1, respectively, suggesting that TRIM28 upregulates TWIST1 post-transcriptionally. Overexpression of TRIM28 in breast cancer cell line promotes cell migration and invasion. Knockdown of TRIM28 reduces the protein level of TWIST1 with concurrent upregulation of E-cadherin and downregulation of N-cadherin and consequently inhibits cell migration and invasion. Furthermore, Immunoprecipitation and GST pull-down assays demonstrated that TRIM28 interacts with TWIST1 directly and this interaction is presumed to protect TWIST1 from degradation. Our study revealed a novel mechanism in breast cancer cells that TRIM28 enhances metastasis by stabilizing TWIST1, suggesting that targeting TRIM28 could be an efficacious strategy in breast cancer treatment. PMID:27412325

  9. Tripartite motif containing 28 (TRIM28) promotes breast cancer metastasis by stabilizing TWIST1 protein

    PubMed Central

    Wei, Chunli; Cheng, Jingliang; Zhou, Boxv; Zhu, Li; Khan, Md. Asaduzzaman; He, Tao; Zhou, Sufang; He, Jian; Lu, Xiaoling; Chen, Hanchun; Zhang, Dianzheng; Zhao, Yongxiang; Fu, Junjiang

    2016-01-01

    TRIM28 regulates its target genes at both transcriptional and posttranscriptional levels. Here we report that a TRIM28-TWIST1-EMT axis exists in breast cancer cells and TRIM28 promotes breast cancer metastasis by stabilizing TWIST1 and subsequently enhancing EMT. We find that TRIM28 is highly expressed in both cancer cell lines and advanced breast cancer tissues, and the levels of TRIM28 and TWIST1 are positively correlated with the aggressiveness of breast carcinomas. Overexpression and depletion of TRIM28 up- and down-regulates the protein, but not the mRNA levels of TWIST1, respectively, suggesting that TRIM28 upregulates TWIST1 post-transcriptionally. Overexpression of TRIM28 in breast cancer cell line promotes cell migration and invasion. Knockdown of TRIM28 reduces the protein level of TWIST1 with concurrent upregulation of E-cadherin and downregulation of N-cadherin and consequently inhibits cell migration and invasion. Furthermore, Immunoprecipitation and GST pull-down assays demonstrated that TRIM28 interacts with TWIST1 directly and this interaction is presumed to protect TWIST1 from degradation. Our study revealed a novel mechanism in breast cancer cells that TRIM28 enhances metastasis by stabilizing TWIST1, suggesting that targeting TRIM28 could be an efficacious strategy in breast cancer treatment. PMID:27412325

  10. Cancer Hallmarks, Biomarkers and Breast Cancer Molecular Subtypes

    PubMed Central

    Dai, Xiaofeng; Xiang, Liangjian; Li, Ting; Bai, Zhonghu

    2016-01-01

    Breast cancer is a complex disease encompassing multiple tumor entities, each characterized by distinct morphology, behavior and clinical implications. Besides estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2, novel biomarkers have shown their prognostic and predictive values, complicating our understanding towards to the heterogeneity of such cancers. Ten cancer hallmarks have been proposed by Weinberg to characterize cancer and its carcinogenesis. By reviewing biomarkers and breast cancer molecular subtypes, we propose that the divergent outcome observed from patients stratified by hormone status are driven by different cancer hallmarks. 'Sustaining proliferative signaling' further differentiates cancers with positive hormone receptors. 'Activating invasion and metastasis' and 'evading immune destruction' drive the differentiation of triple negative breast cancers. 'Resisting cell death', 'genome instability and mutation' and 'deregulating cellular energetics' refine breast cancer classification with their predictive values. 'Evading growth suppressors', 'enabling replicative immortality', 'inducing angiogenesis' and 'tumor-promoting inflammation' have not been involved in breast cancer classification which need more focus in the future biomarker-related research. This review novels in its global view on breast cancer heterogeneity, which clarifies many confusions in this field and contributes to precision medicine. PMID:27390604

  11. Cancer Hallmarks, Biomarkers and Breast Cancer Molecular Subtypes.

    PubMed

    Dai, Xiaofeng; Xiang, Liangjian; Li, Ting; Bai, Zhonghu

    2016-01-01

    Breast cancer is a complex disease encompassing multiple tumor entities, each characterized by distinct morphology, behavior and clinical implications. Besides estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2, novel biomarkers have shown their prognostic and predictive values, complicating our understanding towards to the heterogeneity of such cancers. Ten cancer hallmarks have been proposed by Weinberg to characterize cancer and its carcinogenesis. By reviewing biomarkers and breast cancer molecular subtypes, we propose that the divergent outcome observed from patients stratified by hormone status are driven by different cancer hallmarks. 'Sustaining proliferative signaling' further differentiates cancers with positive hormone receptors. 'Activating invasion and metastasis' and 'evading immune destruction' drive the differentiation of triple negative breast cancers. 'Resisting cell death', 'genome instability and mutation' and 'deregulating cellular energetics' refine breast cancer classification with their predictive values. 'Evading growth suppressors', 'enabling replicative immortality', 'inducing angiogenesis' and 'tumor-promoting inflammation' have not been involved in breast cancer classification which need more focus in the future biomarker-related research. This review novels in its global view on breast cancer heterogeneity, which clarifies many confusions in this field and contributes to precision medicine. PMID:27390604

  12. Effects of irradiation for cervical cancer on subsequent breast cancer

    SciTech Connect

    Harlan, L.C.M.

    1985-01-01

    Previous research suggests that cervical cancer patients have a lower risk of breast cancer than women in the general population. Possible explanations include opposing risk factors for cervical cancer and breast cancer, the effect of irradiation used to treat cervical cancer, or both. The purpose of this study was to explore the relationship between irradiation for cervical cancer and the subsequent development of breast cancer. There was no statistically significant relationship between radiation to the ovarian area and the risk of breast cancer in this study. However, the results were consistent with a 19% reduction in risk for women irradiated for cervical cancer when compared to nonirradiated women. In a dose-response analysis, there was a nonsignificant trend of decreased risk of breast cancer with increased radiation up to 1800 rad. There was no consistent pattern for higher doses. The trend, although nonsignificant, differed by age. Women <60 years of age at irradiation were generally at a lower risk of breast cancer than nonirradiated women. Women over 59 years were at an increased risk. There are some potentially important findings from this study which might influence medical care. These should be examined in the larger International Radiation Study.

  13. Breast Cancer Risk Reduction, Version 2.2015.

    PubMed

    Bevers, Therese B; Ward, John H; Arun, Banu K; Colditz, Graham A; Cowan, Kenneth H; Daly, Mary B; Garber, Judy E; Gemignani, Mary L; Gradishar, William J; Jordan, Judith A; Korde, Larissa A; Kounalakis, Nicole; Krontiras, Helen; Kumar, Shicha; Kurian, Allison; Laronga, Christine; Layman, Rachel M; Loftus, Loretta S; Mahoney, Martin C; Merajver, Sofia D; Meszoely, Ingrid M; Mortimer, Joanne; Newman, Lisa; Pritchard, Elizabeth; Pruthi, Sandhya; Seewaldt, Victoria; Specht, Michelle C; Visvanathan, Kala; Wallace, Anne; Bergman, Mary Ann; Kumar, Rashmi

    2015-07-01

    Breast cancer is the most frequently diagnosed malignancy in women in the United States and is second only to lung cancer as a cause of cancer death. To assist women who are at increased risk of developing breast cancer and their physicians in the application of individualized strategies to reduce breast cancer risk, NCCN has developed these guidelines for breast cancer risk reduction. PMID:26150582

  14. [Special considerations in breast cancer treatment of an augmented breast].

    PubMed

    Mátrai, Zoltán; Gulyás, Gusztáv; Tóth, László; Sávolt, Akos; Kunos, Csaba; Pesthy, Pál; Bartal, Alexandra; Szabó, Eva; Kásler, Miklós

    2011-10-16

    Breast augmentation surgery involving the use of implants has been one of the most popular plastic surgical procedures for decades. As the multi-million female population who received breast implants ages, the risk of cancer is increasing rapidly, therefore the incidence of malignant disease in association with breast implants will increase as well. Although there is no relationship between tumor development and implants, these cases require special considerations in diagnostics, therapy and follow-up methods. Appropriate multidisciplinary treatment of tumors in augmented breasts corresponding with modern oncoplastic principles can only be accomplished based on adequate oncological, breast and plastic surgical knowledge. Supposing a possible increase of this condition in Hungary, too, authors provide a wide review of the literature on the special oncological and esthetic considerations, for the first time in Hungarian language. PMID:21979221

  15. Expression of Polycomb Targets Predicts Breast Cancer Prognosis

    PubMed Central

    Jene-Sanz, Alba; Váraljai, Renáta; Vilkova, Alexandra V.; Khramtsova, Galina F.; Khramtsov, Andrey I.; Olopade, Olufunmilayo I.

    2013-01-01

    Global changes in the epigenome are increasingly being appreciated as key events in cancer progression. The pathogenic role of enhancer of zeste homolog 2 (EZH2) has been connected to its histone 3 lysine 27 (H3K27) methyltransferase activity and gene repression; however, little is known about relationship of changes in expression of EZH2 target genes to cancer characteristics and patient prognosis. Here we show that through expression analysis of genomic regions with H3K27 trimethylation (H3K27me3) and EZH2 binding, breast cancer patients can be stratified into good and poor prognostic groups independent of known cancer gene signatures. The EZH2-bound regions were downregulated in tumors characterized by aggressive behavior, high expression of cell cycle genes, and low expression of developmental and cell adhesion genes. Depletion of EZH2 in breast cancer cells significantly increased expression of the top altered genes, decreased proliferation, and improved cell adhesion, indicating a critical role played by EZH2 in determining the cancer phenotype. PMID:23918806

  16. New targeted therapies for breast cancer: A focus on tumor microenvironmental signals and chemoresistant breast cancers

    PubMed Central

    Kamdje, Armel Hervé Nwabo; Etet, Paul Faustin Seke; Vecchio, Lorella; Tagne, Richard Simo; Amvene, Jeremie Mbo; Muller, Jean-Marc; Krampera, Mauro; Lukong, Kiven Erique

    2014-01-01

    Breast cancer is the most frequent female malignancy worldwide. Current strategies in breast cancer therapy, including classical chemotherapy, hormone therapy, and targeted therapies, are usually associated with chemoresistance and serious adverse effects. Advances in our understanding of changes affecting the interactome in advanced and chemoresistant breast tumors have provided novel therapeutic targets, including, cyclin dependent kinases, mammalian target of rapamycin, Notch, Wnt and Shh. Inhibitors of these molecules recently entered clinical trials in mono- and combination therapy in metastatic and chemo-resistant breast cancers. Anticancer epigenetic drugs, mainly histone deacetylase inhibitors and DNA methyltransferase inhibitors, also entered clinical trials. Because of the complexity and heterogeneity of breast cancer, the future in therapy lies in the application of individualized tailored regimens. Emerging therapeutic targets and the implications for personalized-based therapy development in breast cancer are herein discussed. PMID:25516852

  17. Radiation treatment for breast cancer. Recent advances.

    PubMed Central

    Chow, Edward

    2002-01-01

    OBJECTIVE: To review recent advances in radiation therapy in treatment of breast cancer. QUALITY OF EVIDENCE: MEDLINE and CANCERLIT were searched using the MeSH words breast cancer, ductal carcinoma in situ, sentinel lymph node biopsy, and postmastectomy radiation. Randomized studies have shown the efficacy of radiation treatment for ductal carcinoma in situ (DCIS) and for invasive breast cancer. MAIN MESSAGE: Lumpectomy followed by radiation is effective treatment for DCIS. In early breast cancer, shorter radiation schedules are as efficacious for local control and short-term cosmetic results as traditional fractionation regimens. Sentinel lymph node biopsy is done in specialized cancer centres; regional radiation is recommended for patients with four or more positive axillary lymph nodes. Postmastectomy radiation has been shown to have survival benefits for high-risk premenopausal patients. Systemic metastases from breast cancer usually respond satisfactorily to radiation. CONCLUSION: Radiation therapy continues to have an important role in treatment of breast cancer. There have been great advances in radiation therapy in the last decade, but they have raised controversy. Further studies are needed to address the controversies. PMID:12113193

  18. Managing Breast Cancer in the Older Patient

    PubMed Central

    O’Connor, Tracey; Shinde, Arvind; Doan, Caroline; Katheria, Vani; Hurria, Arti

    2013-01-01

    Breast cancer is a disease associated with aging, with almost one-half of all new breast cancer cases diagnosed annually in the United States occurring in women age 65 and older. Recent data suggest that although breast cancer outcomes in younger women have shown substantial improvement as a result of advances in treatment and screening, the benefits in older women have been less pronounced. Although older adults have been under-represented on cancer clinical trials there is an emerging body of literature to help guide treatment decisions. For early stage breast cancer, the discussion regarding treatment options involves balancing the reduction in risk of recurrence gained by specific therapies with the potential for increased treatment-related toxicity potentially exacerbated by physiological decline or comorbidities that often co-exist in the older population. A key component of care of the older adult is the recognition that chronologic age alone cannot guide the management of an older individual with breast cancer; rather, treatment decisions must also take into account an individual’s functional status, estimated life expectancy, the risks and benefits of the therapy, potential barriers to treatment, and patient preference. This article reviews the available evidence for therapeutic management of early-stage breast cancer in older adults, and highlights data from geriatric oncology literature that provides a basis on which to facilitate evidence-based treatment. PMID:24472802

  19. DNA Repair and Personalized Breast Cancer Therapy

    PubMed Central

    Li, Shu-Xia; Sjolund, Ashley; Harris, Lyndsay; Sweasy, Joann B.

    2010-01-01

    Personalized cancer therapy is likely to be one of the next big advances in our search for a cure for cancer. To be able to treat people in an individualized manner, researchers need to know a great deal about their genetic constitution and the DNA repair status of their tumors. Specific knowledge is required regarding the polymorphisms individuals carry and how these polymorphisms influence responses to therapy. Researchers are actively engaged in biomarker discovery and validation for this purpose. In addition, the design of clinical trials must be reassessed to include new information on biomarkers and drug responses. In this review, we focus on personalized breast cancer therapy. The hypothesis we focus upon in this review is that there is connection between the DNA repair profile of individuals, their breast tumor subtypes, and their responses to cancer therapy. We first briefly review cellular DNA repair pathways that are likely to be impacted by breast cancer therapies. Next, we review the phenotypes of breast tumor subtypes with an emphasis on how a DNA repair deficiency might result in tumorigenesis itself and lead to the chemotherapeutic responses that are observed. Specific examples of breast tumor subtypes and their responses to cancer therapy are given, and we discuss possible DNA repair mechanisms that underlie the responses of tumors to various chemotherapeutic agents. Much is known about breast cancer subtypes and the way each of these subtypes responds to chemotherapy. In addition, we discuss novel design of clinical trials that incorporates rapidly emerging information on biomarkers. PMID:20872853

  20. Knowledge of Breast Cancer and Screening Practices

    ERIC Educational Resources Information Center

    Vahabi, Mandana

    2005-01-01

    Objective: To assess young women's breast health knowledge and explore its relation to the use of screening mammography. Methods: A convenience sample of 180 women aged 25-45 residing in Toronto, Canada, with no history of breast cancer and mammography received an information brochure and four questionnaires which assessed their knowledge of…