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Sample records for 4t1 breast carcinoma

  1. Mono- and Combined Therapy of Metastasizing Breast Carcinoma 4T1 with Zoledronic Acid and Doxorubicin.

    PubMed

    Baklaushev, V P; Grinenko, N F; Yusubalieva, G M; Gubskii, I L; Burenkov, M S; Rabinovich, E Z; Ivanova, N V; Chekhonin, V P

    2016-08-01

    The efficiency of monotherapy with zoledronic acid (Resorba), doxorubicin, and their combination was studied on the model of metastasizing breast carcinoma in BALB/c mice. Doxorubicin monotherapy was accompanied by a significant increase in median survival up to 57 days (vs. 34 and 35 days in control groups); 27% animals survived for 90 days (duration of the study). Bioluminescence area of the primary tumor significantly decreased on days 21 and 28; the total number of visceral metastases also decreased according to magnetic-resonance imaging data. Resorba monotherapy produced no general toxic effect, the median survival increased to 64 days, and 90-day survival was 33%. Imaging techniques (magnetic-resonance imaging, microtomography, bioluminescent analysis) showed that Resorba delayed the development of the primary tumor (regression of luminescence area on days 21 and 28, regression of standardized bioluminescence intensity on day 28) and significantly reduced the number of visceral metastases in comparison with the control. Combination therapy was less effective than monotherapy with the same medications. Median survival was 55 days, 90-day survival was 13%, but magnetic-resonance imaging and bioluminescence analysis after combination therapy also showed delayed growth of the primary tumor and reduced number of visceral metastases. Microtomography revealed bone metastases in ~30% animals of the control group; in experimental groups, no bone metastases were found. The experiment with periosteal (distal epiphysis of the femur) injection of 4T1-Luc2 tumor cells demonstrated pronounced selective effectiveness of Resorba in relation to bone metastases. Monotherapy with Resorba can prevent the development of not only bone, but also visceral metastases of breast cancer. PMID:27590765

  2. Anticancer Activity of Saponins from Allium chinense against the B16 Melanoma and 4T1 Breast Carcinoma Cell

    PubMed Central

    Yu, Zhihui; Zhang, Tong; Zhou, Fengjuan; Xiao, Xiuqing; Ding, Xuezhi; He, Hao; Rang, Jie; Quan, Meifang; Wang, Ting; Zuo, Mingxing; Xia, Liqiu

    2015-01-01

    The cytotoxic substance of A. chinense saponins (ACSs) was isolated using ethanol extraction and purified with the D101 macroporous adsorption resin approach. We investigated the anticancer activity of ACSs in the B16 melanoma and 4T1 breast carcinoma cell lines. Methylthioninium chloride and hematoxylin-eosin staining with Giemsa dyestuff were used when the cells were treated with ACSs. The results showed that the cells morphologies changed significantly; ACSs induced cell death in B16 and 4T1 cells based on acridine orange/ethidium bromide double fluorescence staining, with the number and degree of apoptotic tumor cells increasing as ACS concentration increased. ACSs inhibited the proliferation of B16 and 4T1 cells in a dose-dependent manner. They also inhibited cell migration and colony formation and exhibited a concentration-dependent effect. In addition, ACSs apparently inhibited the growth of melanoma in vivo. The preliminary antitumor in vivo assay revealed that early medication positively affected tumor inhibition action and effectively protected the liver and spleen of C57 BL/6 mice from injury. This study provides evidence for the cytotoxicity of ACSs and a strong foundation for further research to establish the theoretical basis for cell death and help in the design and development of new anticancer drugs. PMID:26146506

  3. Molecular changes in bone marrow, tumor and serum after conductive ablation of murine 4T1 breast carcinoma.

    PubMed

    Przybyla, Beata D; Shafirstein, Gal; Vishal, Sagar J; Dennis, Richard A; Griffin, Robert J

    2014-02-01

    Thermal ablation of solid tumors using conductive interstitial thermal therapy (CITT) produces coagulative necrosis in the center of ablation. Local changes in homeostasis for surviving tumor and systemic changes in circulation and distant organs must be understood and monitored in order to prevent tumor re-growth and metastasis. The purpose of this study was to use a mouse carcinoma model to evaluate molecular changes in the bone marrow and surviving tumor after CITT treatment by quantification of transcripts associated with cancer progression and hyperthermia, serum cytokines, stress proteins and the marrow/tumor cross-talk regulator stromal-derived factor 1. Analysis of 27 genes and 22 proteins with quantitative PCR, ELISA, immunoblotting and multiplex antibody assays revealed that the gene and protein expression in tissue and serum was significantly different between ablated and control mice. The transcripts of four genes (Cxcl12, Sele, Fgf2, Lifr) were significantly higher in the bone marrow of treated mice. Tumors surviving ablation showed significantly lower levels of the Lifr and Sele transcripts. Similarly, the majority of transcripts measured in tumors decreased with treatment. Surviving tumors also contained lower levels of SDF-1α and HIF-1α proteins whereas HSP27 and HSP70 were higher. Of 16 serum chemokines, IFNγ and GM-CSF levels were lower with treatment. These results indicate that CITT ablation causes molecular changes which may slow cancer cell proliferation. However, inhibition of HSP27 may be necessary to control aggressiveness of surviving cancer stem cells. The changes in bone marrow are suggestive of possible increased recruitment of circulatory cancer cells. Therefore, the possibility of heightened bone metastasis after thermal ablation needs to be further investigated and inhibition strategies developed, if warranted. PMID:24270800

  4. PG545, a heparan sulfate mimetic, reduces heparanase expression in vivo, blocks spontaneous metastases and enhances overall survival in the 4T1 breast carcinoma model.

    PubMed

    Hammond, Edward; Brandt, Ralf; Dredge, Keith

    2012-01-01

    PG545 is a clinically relevant heparan sulfate (HS) mimetic which, in addition to possessing anti-angiogenic properties, also acts as a heparanase inhibitor which may differentiate its mechanism(s) of action from approved angiogenesis inhibitors. The degradation of HS by heparanase has been strongly implicated in cell dissemination and the metastatic process. Thus, the anti-metastatic activity of PG545 has been linked to the enzymatic function of heparanase - the only endoglycosidase known to cleave HS, an important component of the extracellular matrix (ECM) which represents a potential avenue for therapeutic intervention for certain metastatic cancer indications. Recent concerns raised about the paucity of overall survival as an endpoint in mouse models of clinically relevant metastasis led us to examine the effect of PG545 on the progression of both primary tumor growth and the spontaneously metastasizing disease in the 4T1 syngeneic breast carcinoma model in a non-surgical and surgical (mastectomy) setting. PG545 significantly inhibited primary tumor growth but importantly also inhibited lung metastasis in treated mice, an effect not observed with the tyrosine kinase inhibitor sorafenib. Importantly, PG545 significantly enhanced overall survival compared to vehicle control and the sorafenib group, suggesting PG545's inhibitory effect on heparanase is indeed a critical attribute to induce anti-metastatic activity. In addition to blocking a common angiogenic signalling pathway in tumor cells, the expression of heparanase in the primary tumor and lung was also significantly reduced by PG545 treatment. These results support the ongoing development of PG545 and highlight the potential utility in metastatic disease settings. PMID:23300607

  5. Murine breast carcinoma 4T1 cells are more sensitive to atranorin than normal epithelial NMuMG cells in vitro: Anticancer and hepatoprotective effects of atranorin in vivo.

    PubMed

    Solár, Peter; Hrčková, Gabriela; Koptašíková, Lenka; Velebný, Samuel; Solárová, Zuzana; Bačkor, Martin

    2016-04-25

    The aim of this study was to evaluate the anticancer effect of atranorin (ATR) on murine 4T1 breast carcinoma cells and compare its sensitivity with normal mammary epithelial NMuMG cells in vitro. Anti-tumor and hepatoprotective activity of ATR-therapy was examined on mouse model of 4T1-induced cancer disease. ATR significantly reduced clonogenic ability of carcinoma 4T1 cells at the concentration of 75 μM, but clonogenicity of normal NMuMG cells was not affected by any of ATR concentrations tested. Moreover, flow cytometric and BrdU incorporation analysis did not confirm the inhibited entry into S-phase of the cell cyle after ATR incubation, and on the contrary, it induced apoptosis associated with the activation of caspase-3 and PARP cleavage in 4T1 cells. Although ATR did not cause any significant changes in Bcl-xL protein expression in NMuMG cells, an apparent depletion of Bcl-xL protein in 4T1 cells after 48 h ATR therapy was confirmed. Based on this result as well as the result of the total cell number decline, we can conclude that 4T1 cells are more sensitive to ATR therapy than NMuMG cells. ATR administration resulted in significantly longer survival time of BALB/c mice inoculated with 4T1 cells, what was associated with reduced tumor size and the higher numbers of apoptotic 4T1 cells. No differences were recorded in the number of BrdU-positive tumor cells between ATR-treated group and controls. Results indicate that ATR has rather proapoptotic than antiproliferative effect on 4T1 cells in vitro and in vivo and normal NMuMG cells are less sensitive to ATR. Furthermore, our studies revealed protective effect of ATR against oxidative stress in the livers of the tumor-bearing mice. PMID:26969521

  6. Secretion of N- and O-linked Glycoproteins from 4T1 Murine Mammary Carcinoma Cells

    PubMed Central

    Phang, Wai-Mei; Tan, Aik-Aun; Gopinath, Subash C.B.; Hashim, Onn H.; Kiew, Lik Voon; Chen, Yeng

    2016-01-01

    Breast cancer is one of the most common cancers that affect women globally and accounts for ~23% of all cancers diagnosed in women. Breast cancer is also one of the leading causes of death primarily due to late stage diagnoses and a lack of effective treatments. Therefore, discovering protein expression biomarkers is mandatory for early detection and thus, critical for successful therapy. Two-dimensional electrophoresis (2D-E) coupled with lectin-based analysis followed by mass spectrometry were applied to identify potential biomarkers in the secretions of a murine mammary carcinoma cell line. Comparisons of the protein profiles of the murine 4T1 mammary carcinoma cell line and a normal murine MM3MG mammary cell line indicated that cadherin-1 (CDH), collagenase 3 (MMP-13), Viral envelope protein G7e (VEP), Gag protein (GAG) and Hypothetical protein LOC433182 (LOC) were uniquely expressed by the 4T1 cells, and pigment epithelium-derived factor (PEDF) was exclusively secreted by the MM3MG cells. Further analysis by a lectin-based study revealed that aberrant O-glycosylated CDH, N-glycosylated MMP-13 and LOC were present in the 4T1 medium. These differentially expressed N- and O-linked glycoprotein candidates, which were identified by combining lectin-based analysis with 2D-E, could serve as potential diagnostic and prognostic markers for breast cancer. PMID:27226773

  7. Secretion of N- and O-linked Glycoproteins from 4T1 Murine Mammary Carcinoma Cells.

    PubMed

    Phang, Wai-Mei; Tan, Aik-Aun; Gopinath, Subash C B; Hashim, Onn H; Kiew, Lik Voon; Chen, Yeng

    2016-01-01

    Breast cancer is one of the most common cancers that affect women globally and accounts for ~23% of all cancers diagnosed in women. Breast cancer is also one of the leading causes of death primarily due to late stage diagnoses and a lack of effective treatments. Therefore, discovering protein expression biomarkers is mandatory for early detection and thus, critical for successful therapy. Two-dimensional electrophoresis (2D-E) coupled with lectin-based analysis followed by mass spectrometry were applied to identify potential biomarkers in the secretions of a murine mammary carcinoma cell line. Comparisons of the protein profiles of the murine 4T1 mammary carcinoma cell line and a normal murine MM3MG mammary cell line indicated that cadherin-1 (CDH), collagenase 3 (MMP-13), Viral envelope protein G7e (VEP), Gag protein (GAG) and Hypothetical protein LOC433182 (LOC) were uniquely expressed by the 4T1 cells, and pigment epithelium-derived factor (PEDF) was exclusively secreted by the MM3MG cells. Further analysis by a lectin-based study revealed that aberrant O-glycosylated CDH, N-glycosylated MMP-13 and LOC were present in the 4T1 medium. These differentially expressed N- and O-linked glycoprotein candidates, which were identified by combining lectin-based analysis with 2D-E, could serve as potential diagnostic and prognostic markers for breast cancer. PMID:27226773

  8. 4T1 Murine Mammary Carcinoma Cells Enhance Macrophage-Mediated Innate Inflammatory Responses

    PubMed Central

    Madera, Laurence; Greenshields, Anna; Coombs, Melanie R. Power; Hoskin, David W.

    2015-01-01

    Tumor progression and the immune response are intricately linked. While it is known that cancers alter macrophage inflammatory responses to promote tumor progression, little is known regarding how cancers affect macrophage-dependent innate host defense. In this study, murine bone-marrow-derived macrophages (BMDM) were exposed to murine carcinoma-conditioned media prior to assessment of the macrophage inflammatory response. BMDMs exposed to 4T1 mammary carcinoma-conditioned medium demonstrated enhanced production of pro-inflammatory cytokines tumor necrosis factor α, interleukin-6, and CCL2 in response to lipopolysaccharide (LPS) while production of interleukin-10 remained unchanged. The increased LPS-induced production of pro-inflammatory cytokines was transient and correlated with enhanced cytokine production in response to other Toll-like receptor agonists, including peptidoglycan and flagellin. In addition, 4T1-conditioned BMDMs exhibited strengthened LPS-induced nitric oxide production and enhanced phagocytosis of Escherichia coli. 4T1-mediated augmentation of macrophage responses to LPS was partially dependent on the NFκB pathway, macrophage-colony stimulating factor, and actin polymerization, as well as the presence of 4T1-secreted extracellular vesicles. Furthermore, peritoneal macrophages obtained from 4T1 tumor-bearing mice displayed enhanced pro-inflammatory cytokine production in response to LPS. These results suggest that uptake of 4T1-secreted factors and actin-mediated ingestion of 4T1-secreted exosomes by macrophages cause a transient enhancement of innate inflammatory responses. Mammary carcinoma-mediated regulation of innate immunity may have significant implications for our understanding of host defense and cancer progression. PMID:26177198

  9. 4T1 Murine Mammary Carcinoma Cells Enhance Macrophage-Mediated Innate Inflammatory Responses.

    PubMed

    Madera, Laurence; Greenshields, Anna; Coombs, Melanie R Power; Hoskin, David W

    2015-01-01

    Tumor progression and the immune response are intricately linked. While it is known that cancers alter macrophage inflammatory responses to promote tumor progression, little is known regarding how cancers affect macrophage-dependent innate host defense. In this study, murine bone-marrow-derived macrophages (BMDM) were exposed to murine carcinoma-conditioned media prior to assessment of the macrophage inflammatory response. BMDMs exposed to 4T1 mammary carcinoma-conditioned medium demonstrated enhanced production of pro-inflammatory cytokines tumor necrosis factor α, interleukin-6, and CCL2 in response to lipopolysaccharide (LPS) while production of interleukin-10 remained unchanged. The increased LPS-induced production of pro-inflammatory cytokines was transient and correlated with enhanced cytokine production in response to other Toll-like receptor agonists, including peptidoglycan and flagellin. In addition, 4T1-conditioned BMDMs exhibited strengthened LPS-induced nitric oxide production and enhanced phagocytosis of Escherichia coli. 4T1-mediated augmentation of macrophage responses to LPS was partially dependent on the NFκB pathway, macrophage-colony stimulating factor, and actin polymerization, as well as the presence of 4T1-secreted extracellular vesicles. Furthermore, peritoneal macrophages obtained from 4T1 tumor-bearing mice displayed enhanced pro-inflammatory cytokine production in response to LPS. These results suggest that uptake of 4T1-secreted factors and actin-mediated ingestion of 4T1-secreted exosomes by macrophages cause a transient enhancement of innate inflammatory responses. Mammary carcinoma-mediated regulation of innate immunity may have significant implications for our understanding of host defense and cancer progression. PMID:26177198

  10. Selection of Novel Peptides Homing the 4T1 CELL Line: Exploring Alternative Targets for Triple Negative Breast Cancer.

    PubMed

    Silva, Vera L; Ferreira, Debora; Nobrega, Franklin L; Martins, Ivone M; Kluskens, Leon D; Rodrigues, Ligia R

    2016-01-01

    The use of bacteriophages to select novel ligands has been widely explored for cancer therapy. Their application is most warranted in cancer subtypes lacking knowledge on how to target the cancer cells in question, such as the triple negative breast cancer, eventually leading to the development of alternative nanomedicines for cancer therapeutics. Therefore, the following study aimed to select and characterize novel peptides for a triple negative breast cancer murine mammary carcinoma cell line- 4T1. Using phage display, 7 and 12 amino acid random peptide libraries were screened against the 4T1 cell line. A total of four rounds, plus a counter-selection round using the 3T3 murine fibroblast cell line, was performed. The enriched selective peptides were characterized and their binding capacity towards 4T1 tissue samples was confirmed by immunofluorescence and flow cytometry analysis. The selected peptides (4T1pep1 -CPTASNTSC and 4T1pep2-EVQSSKFPAHVS) were enriched over few rounds of selection and exhibited specific binding to the 4T1 cell line. Interestingly, affinity to the human MDA-MB-231 cell line was also observed for both peptides, promoting the translational application of these novel ligands between species. Additionally, bioinformatics analysis suggested that both peptides target human Mucin-16. This protein has been implicated in different types of cancer, as it is involved in many important cellular functions. This study strongly supports the need of finding alternative targeting systems for TNBC and the peptides herein selected exhibit promising future application as novel homing peptides for breast cancer therapy. PMID:27548261

  11. Selection of Novel Peptides Homing the 4T1 CELL Line: Exploring Alternative Targets for Triple Negative Breast Cancer

    PubMed Central

    Nobrega, Franklin L.; Martins, Ivone M.

    2016-01-01

    The use of bacteriophages to select novel ligands has been widely explored for cancer therapy. Their application is most warranted in cancer subtypes lacking knowledge on how to target the cancer cells in question, such as the triple negative breast cancer, eventually leading to the development of alternative nanomedicines for cancer therapeutics. Therefore, the following study aimed to select and characterize novel peptides for a triple negative breast cancer murine mammary carcinoma cell line– 4T1. Using phage display, 7 and 12 amino acid random peptide libraries were screened against the 4T1 cell line. A total of four rounds, plus a counter-selection round using the 3T3 murine fibroblast cell line, was performed. The enriched selective peptides were characterized and their binding capacity towards 4T1 tissue samples was confirmed by immunofluorescence and flow cytometry analysis. The selected peptides (4T1pep1 –CPTASNTSC and 4T1pep2—EVQSSKFPAHVS) were enriched over few rounds of selection and exhibited specific binding to the 4T1 cell line. Interestingly, affinity to the human MDA-MB-231 cell line was also observed for both peptides, promoting the translational application of these novel ligands between species. Additionally, bioinformatics analysis suggested that both peptides target human Mucin-16. This protein has been implicated in different types of cancer, as it is involved in many important cellular functions. This study strongly supports the need of finding alternative targeting systems for TNBC and the peptides herein selected exhibit promising future application as novel homing peptides for breast cancer therapy. PMID:27548261

  12. Rejection of metastatic 4T1 breast cancer by attenuation of Treg cells in combination with immune stimulation.

    PubMed

    Chen, Li; Huang, Tian-Gui; Meseck, Marcia; Mandeli, John; Fallon, John; Woo, Savio L C

    2007-12-01

    4T1 breast carcinoma is a highly malignant and poorly immunogenic murine tumor model that resembles advanced breast cancer in humans, and is refractory to most immune stimulation-based treatments. We hypothesize that the ineffectiveness of immune stimulatory treatment is mediated by the suppressive effects of CD4(+)CD25(+) regulatory T (Treg) cells, which can be attenuated by engaging the glucocorticoid-induced tumor necrosis factor receptor family-related protein with its natural ligand (GITRL); further, combination treatment with existing immune stimulation regimens will augment anti-tumor immunity and eradicate metastatic 4T1 tumors in mice.A soluble homodimeric form of mouse GITRL (mIg-mGITRLs) was molecularly constructed and used to treat orthotopic 4T1 tumors established in immune-competent, syngeneic Balb/c mice. When applied in combination with adenovirus-mediated intratumoral murine granulocyte macrophage colony stimulating factor (GM-CSF) and interleukin-12 (IL-12) gene delivery plus systemic 4-1BB activation, mIg-mGITRLs attenuated the immune-suppressive function of splenic Treg cells, which led to elevated interferon-gamma (IFN-gamma) production, tumor-specific cytolytic T-cell activities, tumor rejection and long-term survival in 65% of the animals without apparent toxicities. The results demonstrate that addition of mIg-mGITRLs to an immune-stimulatory treatment regimen significantly improved long-term survival without apparent toxicity, and could potentially be clinically translated into an effective and safe treatment modality for metastatic breast cancer in patients. PMID:17968355

  13. Imagable 4T1 model for the study of late stage breast cancer

    PubMed Central

    Tao, Kai; Fang, Min; Alroy, Joseph; Sahagian, G Gary

    2008-01-01

    Background The 4T1 mouse mammary tumor cell line is one of only a few breast cancer models with the capacity to metastasize efficiently to sites affected in human breast cancer. Here we describe two 4T1 cell lines modified to facilitate analysis of tumor growth and metastasis and evaluation of gene function in vivo. New information regarding the involvement of innate and acquired immunity in metastasis and other characteristics of the model relevant to its use in the study of late stage breast cancer are reported. Methods The lines were engineered for stable expression of firefly luciferase to allow tracking and quantitation of the cells in vivo. Biophotonic imaging was used to characterize growth and metastasis of the lines in vivo and an improved gene expression approach was used to characterize the basis for the metastatic phenotype that was observed. Results Growth of cells at the primary site was biphasic with metastasis detected during the second growth phase 5–6 weeks after introduction of the cells. Regression of growth, which occurred in weeks 3–4, was associated with extensive necrosis and infiltration of leukocytes. Biphasic tumor growth did not occur in BALB/c SCID mice indicating involvement of an acquired immune response in the effect. Hematopoiesis in spleen and liver and elevated levels of circulating leukocytes were observed at week 2 and increased progressively until death at week 6–8. Gene expression analysis revealed an association of several secreted factors including colony stimulatory factors, cytokines and chemokines, acute phase proteins, angiogenesis factors and ECM modifying proteins with the 4T1 metastatic phenotype. Signaling pathways likely to be responsible for production of these factors were also identified. Conclusion The production of factors that stimulate angiogenesis and ECM modification and induce hematopoiesis, recruitment and activation of leukocytes suggest that 4T1 tumor cells play a more direct role than previously

  14. Relationships between LDH-A, Lactate and Metastases in 4T1 Breast Tumors

    PubMed Central

    Rizwan, Asif; Serganova, Inna; Khanin, Raya; Karabeber, Hazem; Ni, Xiaohui; Thakur, Sunitha; Zakian, Kristen L.; Blasberg, Ronald; Koutcher, Jason A.

    2013-01-01

    Purpose To investigate the relationship between LDH-A expression, lactate concentration, cell metabolism and metastases in murine 4T1 breast tumors. Experimental Design Inhibition of LDH-A expression and protein levels were achieved in a metastatic breast cancer cell line (4T1) using shRNA technology. The relationship between tumor LDH-A protein levels and lactate concentration (measured by magnetic resonance spectroscopic imaging-MRSI) and metastases was assessed. Results LDH-A knockdown cells (KD9) showed a significant reduction in LDH-A protein and LDH activity, less acid production, decreased transwell migration and invasion, lower proliferation, reduced glucose utilization and glycolysis and increase in oxygen consumption, ROS and cellular ATP levels, compared to control (NC) cells cultured in 25 mM glucose. In vivo studies showed lower lactate levels in KD9, KD5, KD317 tumors than in NC or 4T1 wild-type tumors (p<0.01), and a linear relationship between tumor LDH-A protein expression and lactate concentration. Metastases were delayed and primary tumor growth rate decreased. Conclusions We show for the first time that LDH-A knockdown inhibited the formation of metastases, and was accompanied by in vivo changes in tumor cell metabolism. Lactate MRSI can be used as a surrogate to monitor targeted inhibition of LDH-A in a pre-clinical setting and provides a non-invasive imaging strategy to monitor LDH-A targeted therapy. This imaging strategy can be translated to the clinic to identify and monitor patients who are at high risk of developing metastatic disease. PMID:23833310

  15. Oral administration of 3,3'-diindolylmethane inhibits lung metastasis of 4T1 murine mammary carcinoma cells in BALB/c mice.

    PubMed

    Kim, Eun Ji; Shin, Minjeong; Park, Heesook; Hong, Ji Eun; Shin, Hyun-Kyung; Kim, Jongdai; Kwon, Dae Young; Park, Jung Han Yoon

    2009-12-01

    3,3'-diindolylmethane (DIM) is the major in vivo product of the acid-catalyzed oligomerization of indole-3-carbinol present in cruciferous vegetables, and it has been shown to exhibit anticancer properties. In this study, we assessed the effects of DIM on the metastasis of 4T1 mouse mammary carcinoma cells. In vitro culture studies showed that DIM dose-dependently inhibited the migration, invasion, and adhesion of 4T1 cells at concentrations of 0-10 micromol/L without attendant changes in cell viability. In an in vivo lung metastasis model, 4T1 cells (2 x 10(5) cells/mouse) were injected into the tail veins of syngeneic female BALB/c mice. Beginning on the second day, the mice were subjected to gavage with 0-10 mg DIM/(kg body weight x d) for 13 d. Oral DIM administration resulted in a marked reduction in the number of pulmonary tumor nodules. DIM treatment significantly reduced the levels of matrix metalloproteinase (MMP)-2, MMP-9, tissue inhibitor of metalloproteinase (TIMP)-1, and vascular cell adhesion molecule (VCAM)-1 and increased TIMP-2 levels in the sera and lungs of mice injected with 4T1 cells. Additionally, DIM treatment reduced the serum concentrations of interleukin (IL)-1beta, IL-6 and tumor necrosis factor (TNF)alpha. We have demonstrated that DIM profoundly inhibits the lung metastasis of 4T1 cells, which was accompanied by reduced levels of MMP, adhesion molecules, and proinflammatory cytokines. These results indicate that DIM has potential as an antimetastatic agent for the treatment of breast cancer. PMID:19864400

  16. A novel protein with anti-metastasis activity on 4T1 carcinoma from medicinal fungus Cordyceps militaris.

    PubMed

    Yang, Qing; Yin, Yalin; Yu, Guojun; Jin, Yanxia; Ye, Xiangdong; Shrestha, Alok; Liu, Wei; Yu, Wenhui; Sun, Hui

    2015-09-01

    Cordyceps militaris is a famous fungus used in traditional Chinese medicine for nearly one thousand years. And its fruiting body is known to possess anticancer and immunomodulatory activities. This study describes the isolation, characterization, and test of antitumor activity of a C. militaris protein, called here as "C. militaris immunoregulatory protein" (CMIP). CMIP was purified through a three-step chromatographic procedure. The MS analyses showed that CMIP corresponded to an uncharacterized protein (CCM_01955) in the C. militaris transcriptional database. Circular dichroism of CMIP revealed the composition of 35.5% β-sheet, 18.5% α-helix, 17.0% turn and 29.0% random coil. No significant cytotoxicity of CMIP was observed on HeLa, HepG2 and 4T1 tumor cells. However, CMIP demonstrated anti-metastasis activity on a mouse model of 4T1 breast cancer lung metastasis. It reduced the number of tumor nodules in the lung of tumor-bearing mice and prolonged their survival time. Furthermore, proliferation of the 4T1 cells was inhibited by macrophage-CMIP conditioned media. And the mRNA levels of cytokines TNF-α, IL-1β and IL-6 were increased significantly in peritoneal macrophages treated by CMIP. These results reveal the antitumor potential of CMIP, thus reinforcing the importance of biochemical prospecting of C. militaris. PMID:26136144

  17. Downregulation of CD73 in 4T1 breast cancer cells through siRNA-loaded chitosan-lactate nanoparticles.

    PubMed

    Jadidi-Niaragh, Farhad; Atyabi, Fatemeh; Rastegari, Ali; Mollarazi, Esmail; Kiani, Melika; Razavi, Alireza; Yousefi, Mehdi; Kheshtchin, Nasim; Hassannia, Hadi; Hadjati, Jamshid; Shokri, Fazel

    2016-06-01

    The immunosuppressive factors in tumor microenvironment enhance tumor growth and suppress anti-tumor immune responses. Adenosine is an important immunosuppressive factor which can be secreted by both tumor and immune cells trough action of two cell surface ecto-nucleotidase molecules CD39 and CD73. Blocking the adenosine generating molecules has emerged as an effective immunotherapeutic approach for treatment of cancer. In this study, CD73-siRNA encapsulated into chitosan-lactate (ChLa) nanoparticles (NPs) was employed to suppress the expression of CD73 molecule on 4T1 breast tumor cells, in vitro. ChLa NPs were generated through ionic gelation of ChLa by tripolyphosphate (TPP). Small interfering RNA (SiRNA)-loaded NPs had about 100 nm size with a polydispersive index below 0.3 and a zeta potential about 13. Our results showed that ChLa NPs with Ch 50 kDa exhibit the best physicochemical features with the high siRNA encapsulation capacity. Synthesized NPs were able to fully bind with siRNA, protect them against serum and heparin degradation, and promote the transfection process. While the NPs exhibited low toxicity during 72 h cell culture, the transfection of Ch-plasmid expressing green fluorescent protein (pEGFP) NPs was efficient in 4T1 cells with a transfection rate of 53.6 % as detected by flow cytometry. In addition, CD73-siRNA-loaded ChLa NPs could efficiently suppress the expression of CD73 as assayed by real-time polymerase chain reaction and flow cytometry. As a conclusion, CD73-siRNA-loaded ChLa NPs may be considered as a promising therapeutic tool for cancer therapy; however, further in vivo investigations are necessary. PMID:26733167

  18. In vivo antitumor and antimetastatic effects of flavokawain B in 4T1 breast cancer cell-challenged mice

    PubMed Central

    Abu, Nadiah; Mohamed, Nurul Elyani; Yeap, Swee Keong; Lim, Kian Lam; Akhtar, M Nadeem; Zulfadli, Aimi Jamil; Kee, Beh Boon; Abdullah, Mohd Puad; Omar, Abdul Rahman; Alitheen, Noorjahan Banu

    2015-01-01

    Flavokawain B (FKB) is a naturally occurring chalcone that can be isolated through the root extracts of the kava-kava plant (Piper methysticum). It can also be synthesized chemically to increase the yield. This compound is a promising candidate as a biological agent, as it is reported to be involved in a wide range of biological activities. Furthermore, FKB was reported to have antitumorigenic effects in several cancer cell lines in vitro. However, the in vivo antitumor effects of FKB have not been reported on yet. Breast cancer is one of the major causes of cancer-related deaths in the world today. Any potential treatment should not only impede the growth of the tumor, but also modulate the immune system efficiently and inhibit the formation of secondary tumors. As presented in our study, FKB induced apoptosis in 4T1 tumors in vivo, as evidenced by the terminal deoxynucleotidyl transferase dUTP nick end labeling and hematoxylin and eosin staining of the tumor. FKB also regulated the immune system by increasing both helper and cytolytic T-cell and natural killer cell populations. In addition, FKB also enhanced the levels of interleukin 2 and interferon gamma but suppressed interleukin 1B. Apart from that, FKB was also found to inhibit metastasis, as evaluated by clonogenic assay, bone marrow smearing assay, real-time polymerase chain reaction, Western blot, and proteome profiler analysis. All in all, FKB may serve as a promising anticancer agent, especially in treating breast cancer. PMID:25834398

  19. Aspirin Breaks the Crosstalk between 3T3-L1 Adipocytes and 4T1 Breast Cancer Cells by Regulating Cytokine Production.

    PubMed

    Hsieh, Chia-Chien; Huang, Yu-Shan

    2016-01-01

    Breast cancer is one of the most common cancers in women worldwide. The obesity process is normally accompanied by chronic, low-grade inflammation. Infiltration by inflammatory cytokines and immune cells provides a favorable microenvironment for tumor growth, migration, and metastasis. Epidemiological evidence has shown that aspirin is an effective agent against several types of cancer. The aim of this study is to investigate the anti-inflammatory and anti-cancer effects of aspirin on 3T3-L1 adipocytes, 4T1 murine breast cancer cells, and their crosstalk. The results showed that aspirin treatment inhibited differentiation and lipid accumulation by 3T3-L1 preadipocytes, and decreased the secretion of the inflammatory adipokine MCP-1 after stimulation with tumor necrosis factor (TNF)-α or conditioned medium from RAW264.7 cells. In 4T1 cells, treatment with aspirin decreased cell viability and migration, possibly by suppressing MCP-1 and VEGF secretion. Subsequently, culture of 4T1 cells in 3T3-L1 adipocyte-conditioned medium (Ad-CM) and co-culture of 3T3-L1 and 4T1 cells using a transwell plate were performed to clarify the relationship between these two cell lines. Aspirin exerted its inhibitory effects in the transwell co-culture system, as well as the conditioned-medium model. Aspirin treatment significantly inhibited the proliferation of 4T1 cells, and decreased the production of MCP-1 and PAI-1 in both the Ad-CM model and co-culture system. Aspirin inhibited inflammatory MCP-1 adipokine production by 3T3-L1 adipocytes and the cell growth and migration of 4T1 cells. It also broke the crosstalk between these two cell lines, possibly contributing to its chemopreventive properties in breast cancer. This is the first report that aspirin's chemopreventive activity supports the potential application in auxiliary therapy against obesity-related breast cancer development. PMID:26794215

  20. Suppressive effects of a proton beam on tumor growth and lung metastasis through the inhibition of metastatic gene expression in 4T1 orthotopic breast cancer model.

    PubMed

    Kwon, Yun-Suk; Lee, Kyu-Shik; Chun, So-Young; Jang, Tae Jung; Nam, Kyung-Soo

    2016-07-01

    A proton beam is a next generation tool to treat intractable cancer. Although the therapeutic effects of a proton beam are well known, the effect on tumor metastasis is not fully described. Here, we investigated the effects of a proton beam on metastasis in highly invasive 4T1 murine breast cancer cells and their orthotopic breast cancer model. Cells were irradiated with 2, 4, 8 or 16 Gy proton beam, and changes in cell proliferation, survival, and migration were observed by MTT, colony forming and wound healing assays. 4T1 breast cancer cell-implanted BALB/c mice were established and the animals were randomly divided into 4 groups when tumor size reached 200 mm3. Breast tumors were selectively irradiated with 10, 20 or 30 Gy proton beam. Breast tumor sizes were measured twice a week, and breast tumor and lung tissues were pathologically observed. Metastasis-regulating gene expression was assessed with quantitative RT-PCR. A proton beam dose-dependently decreased cell proliferation, survival and migration in 4T1 murine breast cancer cells. Also, growth of breast tumors in the 4T1 orthotopic breast cancer model was significantly suppressed by proton beam irradiation without significant change of body weight. Furthermore, fewer tumor nodules metastasized from breast tumor into lung in mice irradiated with 30 Gy proton beam, but not with 10 and 20 Gy, than in control. We observed correspondingly lower expression levels of urokinase plasminogen activator (uPA), uPA receptor, cyclooxygenase (COX)-2, and vascular endothelial growth factor (VEGF), which are important factors in cancer metastasis, in breast tumor irradiated with 30 Gy proton beam. Proton beam irradiation did not affect expressions of matrix metalloproteinase (MMP)-9 and MMP-2. Taken together, the data suggest that, although proton beam therapy is an effective tool for breast cancer treatment, a suitable dose is necessary to prevent metastasis-linked relapse and poor prognosis. PMID:27176787

  1. Stromal Integrin α11β1 Affects RM11 Prostate and 4T1 Breast Xenograft Tumors Differently

    PubMed Central

    Skogstrand, Trude; Sortland, Kristina; Schmid, Marei Caroline; Reed, Rolf K.; Stuhr, Linda

    2016-01-01

    Purpose It has been implied that the collagen binding integrin α11β1 plays a role in carcinogenesis. As still relatively little is known about how the stromal integrin α11β1 affects different aspects of tumor development, we wanted to examine the direct effects on primary tumor growth, fibrosis, tumor interstitial fluid pressure (PIF) and metastasis in murine 4T1 mammary and RM11 prostate tumors, using an in vivo SCID integrin α11-deficient mouse model. Methods Tumor growth was measured using a caliper, PIF by the wick-in-needle technique, activated fibroblasts by α-SMA immunofluorescence staining and fibrosis by transmission electron microscopy and picrosirius-red staining. Metastases were evaluated using hematoxylin and eosin stained sections. Results RM11 tumor growth was significantly reduced in the SCID integrin α11-deficient (α11-KO) compared to in SCID integrin α11 wild type (WT) mice, whereas there was no similar effect in the 4T1 tumor model. The 4T1 model demonstrated an alteration in collagen fibril diameter in the integrin α11-KO mice compared to WT, which was not found in the RM11 model. There were no significant differences in the amount of activated fibroblasts, total collagen content, collagen organization or PIF in the tumors in integrin α11-deficient mice compared to WT mice. There was also no difference in lung metastases between the two groups. Conclusion Deficiency of stromal integrin α11β1 showed different effects on tumor growth and collagen fibril diameter depending on tumor type, but no effect on tumor PIF or development of lung metastasis. PMID:26990302

  2. Elimination of the chemotherapy resistant subpopulation of 4T1 mouse breast cancer by haploidentical NK cells cures the vast majority of mice.

    PubMed

    Frings, Peter W H; Van Elssen, Catharina H M J; Wieten, Lotte; Matos, Catarina; Hupperets, Pierre S J G; Schouten, Harry C; Bos, Gerard M J; van Gelder, Michel

    2011-12-01

    Metastatic breast cancer is currently incurable despite initial responsiveness, assumingly due to the presence of chemoresistant subpopulations that can be characterized as label retaining cells (LRC). In the 4T1 mouse breast cancer model, we previously achieved cure after Cyclophosphamide and Total Body Irradiation (CY + TBI) followed by haploidentical bone marrow and spleen transplantation (BMSPLT). CY + TBI without transplantation induced only transient impaired tumor growth indicating a critical role of donor immune cells. As it remained unknown if the 4T1 model resembles human disease with respect to the presence of subpopulations of chemoresistant LRC, we now demonstrate this is indeed the case. Chemoresistance of 4T1 LRC was demonstrated by in vitro co-incubation of fluorescently labeled 4T1 cells in limiting dilution with cyclophosphamide, doxorubicin or cisplatinum, after which only LRC containing colonies remained. LRC also remain in vivo after treatment with CY + TBI. Succeeding experiments set up to identify the haploidentical effector cell responsible for cure and, therefore, for the elimination of chemoresistant LRC designate donor NK cells crucial for the anti-tumor effect. NK cell depletion of the haploidentical graft fully abrogated the anti-tumor effect. Increased disease-free survival retained after transplantation of haploidentical bone marrow and NK cell-enriched spleen cell grafts, even in the absence of donor T-cells or of donor bone marrow. Tumor growth analysis indicates the anti-tumor effect being immediate (days). Based on these data, it is worthwhile to explore alloreactive adoptive NK cell therapy as consolidation for patients with metastasized breast cancer. PMID:21274621

  3. Licoricidin, an Active Compound in the Hexane/Ethanol Extract of Glycyrrhiza uralensis, Inhibits Lung Metastasis of 4T1 Murine Mammary Carcinoma Cells

    PubMed Central

    Park, So Young; Kwon, Soo Jin; Lim, Soon Sung; Kim, Jin-Kyu; Lee, Ki Won; Park, Jung Han Yoon

    2016-01-01

    Licorice extracts containing glycyrrhizin exhibit anti-carcinogenic properties. Because glycyrrhizin induces severe hypokalemia and hypertension, we prepared a hexane/ethanol extract of Glycyrrhiza uralensis (HEGU) that lacks glycyrrhizin, and showed that HEGU induces apoptosis and G1 cell cycle arrest and inhibits migration of DU145 human prostate cancer cells. Our previous in vitro studies identified two active components in HEGU: isoangustone A, which induces apoptosis and G1 cycle arrest, and licoricidin, which inhibits metastasis. This study examined whether HEGU and licoricidin inhibit metastasis using the 4T1 mammary cancer model. Both HEGU and licoricidin treatment reduced pulmonary metastasis and the expression of CD45, CD31, HIF-1α, iNOS, COX-2, and VEGF-A in tumor tissues. Additionally, a decrease in protein expression of VEGF-R2, VEGF-C, VEGF-R3, and LYVE-1 was noted in tumor tissues of licoricidin-treated mice. Furthermore, the blood concentrations of MMP-9, ICAM-1, VCAM-1, and VEGF-A were decreased in HEGU-treated mice. In vitro 4T1 cell culture results showed that both HEGU and licoricidin inhibited cell migration, MMP-9 secretion, and VCAM expression. The present study demonstrates that the licoricidin in HEGU inhibits lung metastasis of 4T1 mammary carcinoma cells, which may be mediated via inhibition of cancer cell migration, tumor angiogenesis, and lymphangiogenesis. PMID:27314329

  4. Licoricidin, an Active Compound in the Hexane/Ethanol Extract of Glycyrrhiza uralensis, Inhibits Lung Metastasis of 4T1 Murine Mammary Carcinoma Cells.

    PubMed

    Park, So Young; Kwon, Soo Jin; Lim, Soon Sung; Kim, Jin-Kyu; Lee, Ki Won; Park, Jung Han Yoon

    2016-01-01

    Licorice extracts containing glycyrrhizin exhibit anti-carcinogenic properties. Because glycyrrhizin induces severe hypokalemia and hypertension, we prepared a hexane/ethanol extract of Glycyrrhiza uralensis (HEGU) that lacks glycyrrhizin, and showed that HEGU induces apoptosis and G1 cell cycle arrest and inhibits migration of DU145 human prostate cancer cells. Our previous in vitro studies identified two active components in HEGU: isoangustone A, which induces apoptosis and G1 cycle arrest, and licoricidin, which inhibits metastasis. This study examined whether HEGU and licoricidin inhibit metastasis using the 4T1 mammary cancer model. Both HEGU and licoricidin treatment reduced pulmonary metastasis and the expression of CD45, CD31, HIF-1α, iNOS, COX-2, and VEGF-A in tumor tissues. Additionally, a decrease in protein expression of VEGF-R2, VEGF-C, VEGF-R3, and LYVE-1 was noted in tumor tissues of licoricidin-treated mice. Furthermore, the blood concentrations of MMP-9, ICAM-1, VCAM-1, and VEGF-A were decreased in HEGU-treated mice. In vitro 4T1 cell culture results showed that both HEGU and licoricidin inhibited cell migration, MMP-9 secretion, and VCAM expression. The present study demonstrates that the licoricidin in HEGU inhibits lung metastasis of 4T1 mammary carcinoma cells, which may be mediated via inhibition of cancer cell migration, tumor angiogenesis, and lymphangiogenesis. PMID:27314329

  5. Radio-photothermal therapy mediated by a single compartment nanoplatform depletes tumor initiating cells and reduces lung metastasis in the orthotopic 4T1 breast tumor model.

    PubMed

    Zhou, Min; Zhao, Jun; Tian, Mei; Song, Shaoli; Zhang, Rui; Gupta, Sanjay; Tan, Dongfeng; Shen, Haifa; Ferrari, Mauro; Li, Chun

    2015-12-14

    Tumor Initiating Cells (TICs) are resistant to radiotherapy and chemotherapy, and are believed to be responsible for tumor recurrence and metastasis. Combination therapies can overcome the limitation of conventional cancer treatments, and have demonstrated promising application in the clinic. Here, we show that dual modality radiotherapy (RT) and photothermal therapy (PTT) mediated by a single compartment nanosystem copper-64-labeled copper sulfide nanoparticles ([(64)Cu]CuS NPs) could suppress breast tumor metastasis through eradication of TICs. Positron electron tomography (PET) imaging and biodistribution studies showed that more than 90% of [(64)Cu]CuS NPs was retained in subcutaneously grown BT474 breast tumor 24 h after intratumoral (i.t.) injection, indicating the NPs are suitable for the combination therapy. Combined RT/PTT therapy resulted in significant tumor growth delay in the subcutaneous BT474 breast cancer model. Moreover, RT/PTT treatment significantly prolonged the survival of mice bearing orthotopic 4T1 breast tumors compared to no treatment, RT alone, or PTT alone. The RT/PTT combination therapy significantly reduced the number of tumor nodules in the lung and the formation of tumor mammospheres from treated 4T1 tumors. No obvious side effects of the CuS NPs were noted in the treated mice in a pilot toxicity study. Taken together, our data support the feasibility of a therapeutic approach for the suppression of tumor metastasis through localized RT/PTT therapy. PMID:26376843

  6. Escherichia coli Nissle 1917 targets and restrains mouse B16 melanoma and 4T1 breast tumors through expression of azurin protein.

    PubMed

    Zhang, Yunlei; Zhang, Youming; Xia, Liqiu; Zhang, Xiangli; Ding, Xuezhi; Yan, Fu; Wu, Feng

    2012-11-01

    Many studies have demonstrated that intravenously administered bacteria can target and proliferate in solid tumors and then quickly be released from other organs. Here, we employed the tumor-targeting property of Escherichia coli Nissle 1917 to inhibit mouse B16 melanoma and 4T1 breast tumors through the expression of azurin protein. For this purpose, recombinant azurin-expressing E. coli Nissle 1917 was developed. The levels of in vitro and in vivo azurin secretion in the engineered bacterium were determined by immunochemistry. Our results demonstrated that B16 melanoma and orthotopic 4T1 breast tumor growth were remarkably restrained and pulmonary metastasis was prevented in immunocompetent mice. It is worth noting that this therapeutic effect partially resulted from the antitumor activity of neutrophils and lymphocytes due to inflammatory responses caused by bacterial infections. No toxicity was observed in the animal during the experiments. This study indicates that E. coli Nissle 1917 could be a potential carrier to deliver antitumor drugs effectively for cancer therapy. PMID:22923405

  7. Escherichia coli Nissle 1917 Targets and Restrains Mouse B16 Melanoma and 4T1 Breast Tumors through Expression of Azurin Protein

    PubMed Central

    Zhang, Yunlei; Zhang, Youming; Zhang, Xiangli; Ding, Xuezhi; Yan, Fu; Wu, Feng

    2012-01-01

    Many studies have demonstrated that intravenously administered bacteria can target and proliferate in solid tumors and then quickly be released from other organs. Here, we employed the tumor-targeting property of Escherichia coli Nissle 1917 to inhibit mouse B16 melanoma and 4T1 breast tumors through the expression of azurin protein. For this purpose, recombinant azurin-expressing E. coli Nissle 1917 was developed. The levels of in vitro and in vivo azurin secretion in the engineered bacterium were determined by immunochemistry. Our results demonstrated that B16 melanoma and orthotopic 4T1 breast tumor growth were remarkably restrained and pulmonary metastasis was prevented in immunocompetent mice. It is worth noting that this therapeutic effect partially resulted from the antitumor activity of neutrophils and lymphocytes due to inflammatory responses caused by bacterial infections. No toxicity was observed in the animal during the experiments. This study indicates that E. coli Nissle 1917 could be a potential carrier to deliver antitumor drugs effectively for cancer therapy. PMID:22923405

  8. Radio-photothermal therapy mediated by a single compartment nanoplatform depletes tumor initiating cells and reduces lung metastasis in the orthotopic 4T1 breast tumor model

    NASA Astrophysics Data System (ADS)

    Zhou, Min; Zhao, Jun; Tian, Mei; Song, Shaoli; Zhang, Rui; Gupta, Sanjay; Tan, Dongfeng; Shen, Haifa; Ferrari, Mauro; Li, Chun

    2015-11-01

    Tumor Initiating Cells (TICs) are resistant to radiotherapy and chemotherapy, and are believed to be responsible for tumor recurrence and metastasis. Combination therapies can overcome the limitation of conventional cancer treatments, and have demonstrated promising application in the clinic. Here, we show that dual modality radiotherapy (RT) and photothermal therapy (PTT) mediated by a single compartment nanosystem copper-64-labeled copper sulfide nanoparticles ([64Cu]CuS NPs) could suppress breast tumor metastasis through eradication of TICs. Positron electron tomography (PET) imaging and biodistribution studies showed that more than 90% of [64Cu]CuS NPs was retained in subcutaneously grown BT474 breast tumor 24 h after intratumoral (i.t.) injection, indicating the NPs are suitable for the combination therapy. Combined RT/PTT therapy resulted in significant tumor growth delay in the subcutaneous BT474 breast cancer model. Moreover, RT/PTT treatment significantly prolonged the survival of mice bearing orthotopic 4T1 breast tumors compared to no treatment, RT alone, or PTT alone. The RT/PTT combination therapy significantly reduced the number of tumor nodules in the lung and the formation of tumor mammospheres from treated 4T1 tumors. No obvious side effects of the CuS NPs were noted in the treated mice in a pilot toxicity study. Taken together, our data support the feasibility of a therapeutic approach for the suppression of tumor metastasis through localized RT/PTT therapy.Tumor Initiating Cells (TICs) are resistant to radiotherapy and chemotherapy, and are believed to be responsible for tumor recurrence and metastasis. Combination therapies can overcome the limitation of conventional cancer treatments, and have demonstrated promising application in the clinic. Here, we show that dual modality radiotherapy (RT) and photothermal therapy (PTT) mediated by a single compartment nanosystem copper-64-labeled copper sulfide nanoparticles ([64Cu]CuS NPs) could suppress

  9. Prevention of Metastasis in a 4T1 Murine Breast Cancer Model by Doxorubicin Carried by Folate Conjugated pH Sensitive Polymeric Micelles

    PubMed Central

    Gao, Zhong-Gao; Tian, Li; Hu, Jun; Park, In-Suh; Bae, You Han

    2011-01-01

    This study primarily focused on the anti-metastatic activity of doxorubicin (DOX) loaded in a pH-sensitive mixed polymeric micelle formed from two block polymers: poly(L-lactide) (PLLA) (Mn 3000)-b-poly(ethylene glycol) (PEG) (Mn 2000)-folate and poly(L-histidine) (PHis) (Mn 4700)-b-PEG (Mn 2000). Tumor formation and metastasis in mice were examined using a murine mammary carcinoma cell of 4T1 which is one of the most aggressive metastatic cancer cell lines. The efficacy was evaluated by tumor size, body weight change, survival rate, dorsal skin fold window chamber model, and histological observation of the lung, heart, liver and spleen after treatment with various DOX formulations. When the tumor reached 50–100 mm3 in size, the mice were treated by 4 times at a 3-day interval at a dose of 10 mg DOX/kg. The mixed micelle formulation resulted in retarded tumor growth, no weight loss, and no death for 4–5 weeks. In another set of the in vivo test for histological evaluation of the organs, the mice were similarly treated but the formulations were injected one day after 4T1 cell inoculation. The treatment by DOX loaded mixed micelle showed no apparent metastasis till 28 days. However, significant metastasis to the lung and heart was observed on Day 28 when the mice were treated with DOX carried by PBS, PLLA-b-PEG micelle and PHis-b-PEG micelle. PMID:21295088

  10. Theranostic probe for simultaneous in vivo photoacoustic imaging and confined photothermolysis by pulsed laser at 1064 nm in 4T1 breast cancer model.

    PubMed

    Zhou, Min; Ku, Geng; Pageon, Laura; Li, Chun

    2014-12-21

    Here, we report that polyethylene glycol (PEG)-coated copper(II) sulfide nanoparticles (PEG-CuS NPs) with their peak absorption tuned to 1064 nm could be used both as a contrast agent for photoacoustic tomographic imaging of mouse tumor vasculature and as a mediator for confined photothermolysis of tumor cells in an orthotopic syngeneic 4T1 breast tumor model. PEG-CuS NPs showed stronger photoacoustic signal than hollow gold nanospheres and single-wall carbon nanotubes at 1064 nm. MicroPET imaging of 4T1 tumor-bearing mice showed a gradual accumulation of the NPs in the tumor over time. About 6.5% of injected dose were taken up in each gram of tumor tissue at 24 h after intravenous injection of (64)Cu-labeled PEG-CuS NPs. For both photoacoustic imaging and therapeutic studies, nanosecond (ns)-pulsed laser was delivered with Q-switched Nd:YAG at a wavelength of 1064 nm. Unlike conventional photothermal ablation therapy mediated by continuous wave laser with which heat could spread to the surrounding normal tissue, interaction of CuS NPs with short pulsed laser deliver heat rapidly to the treatment volume keeping the thermal damage confined to the target tissues. Our data demonstrated that it is possible to use a single-compartment nanoplatform to achieve both photoacoustic tomography and highly selective tumor destruction at 1064 nm in small animals. PMID:25379880

  11. Theranostic probe for simultaneous in vivo photoacoustic imaging and confined photothermolysis by pulsed laser at 1064 nm in 4T1 breast cancer model

    NASA Astrophysics Data System (ADS)

    Zhou, Min; Ku, Geng; Pageon, Laura; Li, Chun

    2014-11-01

    Here, we report that polyethylene glycol (PEG)-coated copper(ii) sulfide nanoparticles (PEG-CuS NPs) with their peak absorption tuned to 1064 nm could be used both as a contrast agent for photoacoustic tomographic imaging of mouse tumor vasculature and as a mediator for confined photothermolysis of tumor cells in an orthotopic syngeneic 4T1 breast tumor model. PEG-CuS NPs showed stronger photoacoustic signal than hollow gold nanospheres and single-wall carbon nanotubes at 1064 nm. MicroPET imaging of 4T1 tumor-bearing mice showed a gradual accumulation of the NPs in the tumor over time. About 6.5% of injected dose were taken up in each gram of tumor tissue at 24 h after intravenous injection of 64Cu-labeled PEG-CuS NPs. For both photoacoustic imaging and therapeutic studies, nanosecond (ns)-pulsed laser was delivered with Q-switched Nd:YAG at a wavelength of 1064 nm. Unlike conventional photothermal ablation therapy mediated by continuous wave laser with which heat could spread to the surrounding normal tissue, interaction of CuS NPs with short pulsed laser deliver heat rapidly to the treatment volume keeping the thermal damage confined to the target tissues. Our data demonstrated that it is possible to use a single-compartment nanoplatform to achieve both photoacoustic tomography and highly selective tumor destruction at 1064 nm in small animals.Here, we report that polyethylene glycol (PEG)-coated copper(ii) sulfide nanoparticles (PEG-CuS NPs) with their peak absorption tuned to 1064 nm could be used both as a contrast agent for photoacoustic tomographic imaging of mouse tumor vasculature and as a mediator for confined photothermolysis of tumor cells in an orthotopic syngeneic 4T1 breast tumor model. PEG-CuS NPs showed stronger photoacoustic signal than hollow gold nanospheres and single-wall carbon nanotubes at 1064 nm. MicroPET imaging of 4T1 tumor-bearing mice showed a gradual accumulation of the NPs in the tumor over time. About 6.5% of injected dose were

  12. Effects of letrozole on breast cancer micro-metastatic tumor growth in bone and lung in mice inoculated with murine 4T1 cells.

    PubMed

    Wang, Wendan; Belosay, Aashvini; Yang, Xujuan; Hartman, James A; Song, Huaxin; Iwaniec, Urszula T; Turner, Russell T; Churchwell, Mona I; Doerge, Daniel R; Helferich, William G

    2016-06-01

    Breast cancer (BC) is the leading cancer in women worldwide. Metastasis occurs in stage IV BC with bone and lung being common metastatic sites. Here we evaluate the effects of the aromatase inhibitor letrozole on BC micro-metastatic tumor growth in bone and lung metastasis in intact and ovariectomized (OVX) mice with murine estrogen receptor negative (ER-) BC cells inoculated in tibia. Forty-eight BALB/c mice were randomly assigned to one of four groups: OVX, OVX + Letrozole, Intact, and Intact + Letrozole, and injected with 4T1 cells intra-tibially. Letrozole was subcutaneously injected daily for 23 days at a dose of 1.75 µg/g body weight. Tumor progression was monitored by bioluminescence imaging (BLI). Following necropsy, inoculated tibiae were scanned via µCT and bone response to tumor was scored from 0 (no ectopic mineralization/osteolysis) to 5 (extensive ectopic mineralization/osteolysis). OVX mice had higher tibial pathology scores indicative of more extensive bone destruction than intact mice, irrespective of letrozole treatment. Letrozole decreased serum estradiol levels and reduced lung surface tumor numbers in intact animals. Furthermore, mice receiving letrozole had significantly fewer tumor colonies and fewer proliferative cells in the lung than OVX and intact controls based on H&E and Ki-67 staining, respectively. In conclusion, BC-inoculated OVX animals had higher tibia pathology scores than BC-inoculated intact animals and letrozole reduced BC metastases to lungs. These findings suggest that, by lowering systemic estrogen level and/or by interacting with the host organ, the aromatase inhibitor letrozole has the potential to reduce ER- BC metastasis to lung. PMID:27209469

  13. Hybrid paclitaxel and gold nanorod-loaded human serum albumin nanoparticles for simultaneous chemotherapeutic and photothermal therapy on 4T1 breast cancer cells.

    PubMed

    Peralta, Donna V; Heidari, Zahra; Dash, Srikanta; Tarr, Matthew A

    2015-04-01

    The use of human serum albumin nanoparticles (HSAPs) as a drug carrier system for cancer treatment has proven successful through current marketable clinical formulations. Despite this success, there is a current lack of multifunctional HSAPs, which offer combinational therapies of more than one proven technique. Gold nanorods (AuNRs) have also shown medicinal promise due to their photothermal therapy capabilities. In this study, a desolvation and cross-linking approach was employed to successfully encapsulate gold nanorods into HSAPs simultaneously with the chemotherapeutic drug paclitaxel (PAC); forming PAC-AuNR-HSAPs with desirable overall particle sizes of 299 ± 6 nm. The loading efficiency of paclitaxel into PAC-AuNR-HSAPs reached up to 3 μg PAC/mg HSA. The PAC-AuNR-HSAPs experienced photothermal heating; with the bulk particle solution reaching up to 46 °C after 15 min of near-IR laser exposure. This heat increase marked the successful attainment of the temperature necessary to cause severe cellular hyperthermia and necrosis. The encasement strategy facilitated a colloidal hybrid treatment system capable of enhanced permeability and retention effects, photothermal ablation of cancer cells, and release of the active paclitaxel of up to 188 ng (from PAC-AuNR-HSAPs created with 30 mg HSA) in a single 15 min irradiation session. When treated with PAC-AuNR-HSAPs containing 20 μg PAC/mL particle solution, 4T1 mouse breast cancer cells experienced ∼82% cell death without irradiation and ∼94% cell death after just one irradiation session. The results for PAC-AuNR-HSAPs were better than that of free PAC, which only killed ∼77% of the cells without irradiation and ∼80% with irradiation. The hybrid particle system also lends itself to future customizable external functionalities via conjugated targeting ligands, such as antibodies. Internal entrapment of patient tailored medication combinations are also possible with this combination treatment platform, which

  14. Low local blood perfusion, high white blood cell and high platelet count are associated with primary tumor growth and lung metastasis in a 4T1 mouse breast cancer metastasis model

    PubMed Central

    WANG, CHUAN; CHEN, YING-GE; GAO, JIAN-LI; LYU, GUI-YUAN; SU, JIE; ZHANG, QI; JI, XIN; YAN, JI-ZHONG; QIU, QIAO-LI; ZHANG, YUE-LI; LI, LIN-ZI; XU, HAN-TING; CHEN, SU-HONG

    2015-01-01

    It was originally thought that no single routine blood test result would be able to indicate whether or not a patient had cancer; however, several novel studies have indicated that the median survival and prognosis of cancer patients were markedly associated with the systemic circulation features of cancer patients. In addition, certain parameters, such as white blood cell (WBC) count, were largely altered in malignant tumors. In the present study, routine blood tests were performed in order to observe the change of blood cells in tumor-bearing mice following the implantation of 4T1 breast cancer cells into the mammary fat pad; in addition, blood flow in breast tumor sites was measured indirectly using laser Doppler perfusion imaging (LDPI), in an attempt to explain the relevance between the blood circulation features and the growth or metastasis of breast cancer in mice model. The LDPI and blood test results indicated that the implantation of 4T1 breast cancer cells into BALB/c mice led to thrombosis as well as high WBC count, high platelet count, high plateletcrit and low blood perfusion. Following implantation of the 4T1 cells for four weeks, the lung metastatic number was determined and the Pearson correlation coefficient revealed that the number of visceral lung metastatic sites had a marked negative association with the ratio of basophils (BASO%; r=-0.512; P<0.01) and the mean corpuscular hemoglobin was significantly correlated with primary tumor weight (r=0.425; P<0.05). In conclusion, the results of the present study demonstrated that tumor growth led to thrombosis and acute anemia in mice; in addition, when blood BASO% was low, an increased number of lung metastases were observed in tumor-bearing mice. PMID:26622565

  15. Comparison patterns of 4 T1 antigens recognized by humoral immune response mediated by IgG and IgM antibodies in female and male mice with breast cancer using 2D-immnunoblots.

    PubMed

    Díaz-Zaragoza, Mariana; Hernández-Ávila, Ricardo; Govezensky, Tzipe; Mendoza, Luis; Meneses-Ruíz, Dulce María; Ostoa-Saloma, Pedro

    2015-09-01

    The early detection of cancer is one of the most promising approaches to reduce its growing burden and develop a curative treatment before the tumor is established. The early diagnosis of breast cancer is the most demanding of all tumors, because it is the most common cancer in women worldwide. We have described a new approach to analyze humoral immune reactions against 4 T1 cell antigens in female mice, reporting that the IgG and IgM responses differed and varied over time and between individuals. In this study, we compared and analyzed the detection of tumor antigens with IgG and IgM from the sera of male mice that were injected with 4 T1 cells into the mammary gland nipple in 2D immunoblot images. The variability in IgM and IgG responses in female and male mice with breast cancer at various stages of disease was characterized, and the properties with regard to antigen recognition were correlated statistically with variables that were associated with the individuals and tumors. The ensuing IgG and IgM responses differed. Only the IgG response decreased over time in female mice--not in male mice. The IgM response was maintained during tumor development in both sexes. Each mouse had a specific pattern of antigen recognition--ie, an immunological signature--represented by a unique set of antigen spots that were recognized by IgM or IgG. These data would support that rationale IgM is a better tool for early diagnosis, because it is not subject to immunosuppression like IgG in female mice with breast cancer. PMID:26026196

  16. Curcumin improves the therapeutic efficacy of Listeriaat-Mage-b vaccine in correlation with improved T-cell responses in blood of a triple-negative breast cancer model 4T1

    PubMed Central

    Singh, Manisha; Ramos, Ilyssa; Asafu-Adjei, Denise; Quispe-Tintaya, Wilber; Chandra, Dinesh; Jahangir, Arthee; Zang, Xingxing; Aggarwal, Bharat B; Gravekamp, Claudia

    2013-01-01

    Abstract Success of cancer vaccination is strongly hampered by immune suppression in the tumor microenvironment (TME). Interleukin (IL)-6 is particularly and highly produced by triple-negative breast cancer (TNBC) cells, and has been considered as an important contributor to immune suppression in the TME. Therefore, we hypothesized that IL-6 reduction may improve efficacy of vaccination against TNBC cancer through improved T-cell responses. To prove this hypothesis, we investigated the effect of curcumin, an inhibitor of IL-6 production, on vaccination of a highly attenuated Listeria monocytogenes (Listeriaat), encoding tumor-associated antigens (TAA) Mage-b in a TNBC model 4T1. Two therapeutic vaccination strategies with Listeriaat-Mage-b and curcumin were tested. The first immunization strategy involved all Listeriaat-Mage-b vaccinations and curcumin after tumor development. As curcumin has been consumed all over the world, the second immunization strategy involved curcumin before and all therapeutic vaccinations with Listeriaat-Mage-b after tumor development. Here, we demonstrate that curcumin significantly improves therapeutic efficacy of Listeriaat-Mage-b with both immunization strategies particularly against metastases in a TNBC model (4T1). The combination therapy was slightly but significantly more effective against the metastases when curcumin was administered before compared to after tumor development. With curcumin before tumor development in the combination therapy, the production of IL-6 was significantly decreased and IL-12 increased by myeloid-derived suppressor cells (MDSC), in correlation with improved CD4 and CD8 T-cell responses in blood. Our study suggests that curcumin improves the efficacy of Listeriaat-Mage-b vaccine against metastases in TNBC model 4T1 through reversal of tumor-induced immune suppression. This study is focused on improving cancer vaccination by reducing immune suppression. Here we demonstrate that curcumin improves vaccine

  17. Cutaneous metastatic pigmented breast carcinoma.

    PubMed

    Gaitan-Gaona, Francisco; Said, Mirra C; Valdes-Rodriguez, Rodrigo

    2016-01-01

    A 66-year-old woman presented with a 3 cm black, ulcerated nodule located on the skin of the upper abdomen, just below the breast. The lesion was painful to the touch, but the patient reported no other associated symptoms and was otherwise healthy. A 4-mm punch biopsy of the affected skin was obtained and the histological diagnosis was cutaneous metastatic pigmented breast carcinoma. PMID:27136637

  18. Carcinoma in accessory axillary breast.

    PubMed

    Khanna, Seema; Mishra, Shashi Prakash; Kumar, Satendra; Khanna, Ajay Kumar

    2015-01-01

    We present a rare case of carcinoma developing in an accessory breast. The patient presented with a progressive lump in her right axilla for 1 year. On examination, there was a well-developed nipple areola complex in the right axilla overlying a hard, fixed 5 × 3 cm lump. On investigation, core biopsy revealed poorly differentiated carcinoma of the breast. Mammography also revealed features of a malignant lesion with skin and muscle infiltration. Neoadjuvant chemotherapy was administered followed by modified radical mastectomy after three cycles. Immunohistochemistry study showed positive status of oestrogen and progesterone receptors, and negative HER-2 neu. Three more cycles of chemotherapy along with 50 Gy radiotherapy were given in an adjuvant setting followed by hormone therapy. PMID:26260957

  19. [Breast carcinoma in the elderly].

    PubMed

    Amodeo, C; Caglià, P; Gandolfo, L; Cardillo, P; Veroux, M

    2002-01-01

    Breast cancer represents 40% of all carcinomas and is responsible for the 20% of deads due to a cancer in female population. Patients in more of 50% age over 65 years. 150 patients with breast cancer older then 65 years underwent surgery. T1 and T2 < 2 cm patients were treated with quadrantectomy and radiotherapy. T2 > 2 cm and T3 patients underwent radical mastectomy. T4 patients were treated with neoadjuvant chemotherapy before surgery. Mean follow up was 48 (range 12-78) months. 43 patients (28.6%) had a progression of the neoplasia. Five years mortality rate was 18.6%. Surgery nowadays represents the treatment of choice for breast cancer even in elderly woman. Associated diseases in these patients shouldn't always considered an absolute contraindication for surgery. PMID:12704991

  20. Anti-tumor effects of DNA vaccine targeting human fibroblast activation protein α by producing specific immune responses and altering tumor microenvironment in the 4T1 murine breast cancer model.

    PubMed

    Xia, Qiu; Zhang, Fang-Fang; Geng, Fei; Liu, Chen-Lu; Xu, Ping; Lu, Zhen-Zhen; Yu, Bin; Wu, Hui; Wu, Jia-Xin; Zhang, Hai-Hong; Kong, Wei; Yu, Xiang-Hui

    2016-05-01

    Fibroblast activation protein α (FAPα) is a tumor stromal antigen overexpressed by cancer-associated fibroblasts (CAFs). CAFs are genetically more stable compared with the tumor cells and immunosuppressive components of the tumor microenvironment, rendering them excellent targets for cancer immunotherapy. DNA vaccines are widely applied due to their safety. To specifically destroy CAFs, we constructed and examined the immunogenicity and anti-tumor immune mechanism of a DNA vaccine expressing human FAPα. This vaccine successfully reduced 4T1 tumor growth through producing FAPα-specific cytotoxic T lymphocyte responses which could kill CAFs, and the decrease in FAPα-expressing CAFs resulted in markedly attenuated expression of collagen I and other stromal factors that benefit the tumor progression. Based on these results, a DNA vaccine targeting human FAPα may be an attractive and effective cancer immunotherapy strategy. PMID:27020681

  1. Inflammatory Breast Carcinoma Presenting with Two Different Patterns of Cutaneous Metastases: Carcinoma Telangiectaticum and Carcinoma Erysipeloides

    PubMed Central

    Yaghoobi, Reza; Talaizade, Abdolhasan; Lal, Karan; Ranjbari, Nastaran; Sohrabiaan, Nasibe

    2015-01-01

    Cutaneous metastases can have many different clinical presentations. They are seen in patients with advanced malignant disease; however, they can be the initial manifestation of undetected malignancies. Inflammatory breast carcinoma is a rare and aggressive form of breast cancer that has a nonspecific appearance mimicking many benign conditions including mastitis, breast abscesses, and/or dermatitis. The authors report the case of a 40-year-old woman with inflammatory breast carcinoma presenting with violaceous papulovesicular lesions resembling lymphangioma circumscriptum and erythematous patches resembling erysipelas. These lesions represent two different types of cutaneous metastases, both of which were the initial signs of inflammatory breast carcinoma in the patient described herein. Skin biopsy of lesions confirmed invasive breast cancer and further prompted a work up for inflammatory breast carcinoma. This case demonstrates the importance of follow-up for all breast lesions, even those considered to be of benign nature, for they can be presenting signs of metastatic breast cancer. PMID:26345728

  2. GATA3 immunohistochemistry expression in histologic subtypes of primary breast carcinoma and metastatic breast carcinoma cytology.

    PubMed

    Deftereos, Georgios; Sanguino Ramirez, Angela M; Silverman, Jan F; Krishnamurti, Uma

    2015-09-01

    GATA3 plays a role in cell proliferation and differentiation in many tissues, including breast, and it has been suggested that GATA3 expression correlates with ER expression. However, little is known on GATA3 expression in various subtypes of breast carcinoma, its utilization in cytology, and on how GATA3 performs in comparison with GCDFP-15 and mammaglobin. Eighty-four histology cases of breast carcinoma of various subtypes, including 28 triple-negative breast carcinomas, along with 20 cytology cases of metastatic breast carcinoma and 12 cytology cases of ER-positive metastatic gynecologic malignancies, were stained for GATA3, GCDFP-15, and mammaglobin. In non-triple-negative breast carcinomas (n=56), GATA3 showed 100% sensitivity, higher than GCDFP-15 (42.8%; P<0.0001) and mammaglobin (58.9%; P<0.0001), whereas staining patterns were similar for all the histologic subtypes examined. Staining scores were determined by multiplying the percentage of cancer cells staining with an intensity score of 1+, 2+, or 3+ (range, 0 to 300). In non-triple-negative carcinomas, GATA3 showed a mean score of 273.7, higher than GCDFP-15 (107.5; P<0.0001) and mammaglobin (147.7; P<0.0001). In triple-negative breast carcinomas (n=28), GATA3 showed a sensitivity of 60.7%, greater than GCDFP-15 (17.9%; P=0.0022) and mammaglobin (7.1%; P<0.0001). These results were consistent irrespective of the subtype examined. In breast carcinoma cytology cases, 100% stained with GATA3, higher than GCDFP-15 (20%; P<0.0001) and mammaglobin (45%; P<0.0001). None of the metastatic endometrial or ovarian carcinomas were positive for GATA3. Although GATA3 expression correlates with ER expression in breast, no correlation is observed in gynecologic malignancies. Thus, in working up ER-positive metastatic malignancies GATA3 demonstrates specificity for breast. PMID:26274030

  3. Spectral morphometric characterization of breast carcinoma cells

    PubMed Central

    Barshack, I; Kopolovic, J; Malik, Z; Rothmann, C

    1999-01-01

    The spectral morphometric characteristics of standard haematoxylin and eosin breast carcinoma specimens were evaluated by light microscopy combined with a spectral imaging system. Light intensity at each wavelength in the range of 450–800 nm was recorded for 104 pixels from each field and represented as transmitted light spectra. A library of six characteristic spectra served to scan the cells and reconstruct new images depicting the nuclear area occupied by each spectrum. Fifteen cases of infiltrating ductal carcinoma and six cases of lobular carcinoma were examined; nine of the infiltrating ductal carcinoma and three of the lobular carcinoma showed an in situ component. The spectral morphometric analysis revealed a correlation between specific patterns of spectra and different groups of breast carcinoma cells. The most consistent result was that lobular carcinoma cells of in situ and infiltrating components from all patients showed a similar spectral pattern, whereas ductal carcinoma cells displayed spectral variety. Comparison of the in situ and the infiltrating ductal solid, cribriform and comedo carcinoma cells from the same patient revealed a strong similarity of the spectral elements and their relative distribution in the nucleus. The spectrum designated as number 5 in the library incorporated more than 40% of the nuclear area in 74.08% of the infiltrating lobular cells and in 13.64% of the infiltrating ductal carcinoma cells (P < 0.001). Spectrum number 2 appeared in all infiltrating ductal cells examined and in none of the lobular cells. These results indicate that spectrum number 5 is related to infiltrating lobular carcinoma, whereas spectrum number 2 is characteristic for infiltrating ductal carcinoma cells. Spectral similarity mapping of central necrotic regions of comedo type in situ carcinoma revealed nuclear fragmentation into defined segments composed of highly condensed chromatin. We conclude that the spectral morphometric features found for

  4. Markers of metastatic carcinoma of breast origin.

    PubMed

    Gown, Allen M; Fulton, Regan S; Kandalaft, Patricia L

    2016-01-01

    This review summarizes the three major breast-associated markers that can be of assistance in evaluating metastatic carcinomas for which a breast primary diagnosis is entertained. These markers include gross cystic disease fluid protein-15 (GCDFP-15), mammaglobin, and GATA3. The first two are cytoplasmic markers that show comparable sensitivities for breast cancer, although relatively few of the published studies have employed the same antibodies against the target molecule, making direct comparisons challenging. GATA3 is a nuclear transcription factor that shows superior sensitivity to GCDFP-15 and mammaglobin. However, the specificity of GATA3 can pose challenges, inasmuch as carcinomas of the bladder and other sites can show significant levels of positivity. Determination of the optimal panel of antibodies employed in a given clinical setting will thus depend on the non-breast tumours included in the differential diagnosis. PMID:26768031

  5. Fungating accessory breast carcinoma in Nigerian women.

    PubMed

    Badejo, O A

    1984-03-01

    Three cases of fungating accessory breast carcinoma out of a total of 22 malignant breast formations seen and treated in Ile-Ife, Nigeria between January 1977 and November 1981 are described. The clinical presentations, features and histologic findings are presented. The methods of management and the need for close observation as well as follow up for at least two years is emphasized. A frequency of 14% as seen in this series appears so high that one cannot describe the occurrence of malignant changes in the accessory breast as rare. PMID:6328710

  6. Metastatic Breast Carcinoma to the Prostate Gland.

    PubMed

    Kapp, Meghan E; Giannico, Giovanna A; Desouki, Mohamed Mokhtar

    2016-01-01

    Cancer of the male breast is an uncommon event with metastases to the breast occurring even less frequently. Prostate carcinoma has been reported as the most frequent primary to metastasize to the breast; however, the reverse has not been previously reported. Herein, we present, for the first time, a case of breast carcinoma metastasizing to the prostate gland. Prostate needle core biopsy revealed infiltrative nests of neoplastic epithelioid cells, demonstrated by immunohistochemistry (IHC) to be positive for GATA3 and ER and negative for PSA and P501S. A prostate cocktail by IHC study demonstrated lack of basal cells (p63 and CK903) and no expression of P501S. The patient's previous breast needle core biopsy showed strong ER positivity and negative staining for PR and HER2. Similar to the prostate, the breast was negative for CK5/6, p63, and p40. This case demonstrates the importance of considering a broad differential diagnosis and comparing histology and IHC to prior known malignancies in the setting of atypical presentation or rare tumors. PMID:27429817

  7. Metastatic Breast Carcinoma to the Prostate Gland

    PubMed Central

    Kapp, Meghan E.

    2016-01-01

    Cancer of the male breast is an uncommon event with metastases to the breast occurring even less frequently. Prostate carcinoma has been reported as the most frequent primary to metastasize to the breast; however, the reverse has not been previously reported. Herein, we present, for the first time, a case of breast carcinoma metastasizing to the prostate gland. Prostate needle core biopsy revealed infiltrative nests of neoplastic epithelioid cells, demonstrated by immunohistochemistry (IHC) to be positive for GATA3 and ER and negative for PSA and P501S. A prostate cocktail by IHC study demonstrated lack of basal cells (p63 and CK903) and no expression of P501S. The patient's previous breast needle core biopsy showed strong ER positivity and negative staining for PR and HER2. Similar to the prostate, the breast was negative for CK5/6, p63, and p40. This case demonstrates the importance of considering a broad differential diagnosis and comparing histology and IHC to prior known malignancies in the setting of atypical presentation or rare tumors. PMID:27429817

  8. Current management of carcinoma of the breast.

    PubMed Central

    Eberlein, T J

    1994-01-01

    OBJECTIVE: An in-depth retrospective review of the multidisciplinary approach to the management of carcinoma of the breast was done. The author reviewed previous trials and treatment from the past to the present. The indications and contraindications of surgical procedures, radiation therapy, systemic chemotherapy, and hormonal therapy are discussed. SUMMARY BACKGROUND DATA: Carcinoma of the breast is one of the most common malignancies treated by the practicing general or oncologic surgeon. The disease is best treated using a multidisciplinary approach, combining the efforts of surgery, radiation therapy, and systemic treatments. Understanding the indications and contraindications for each of these modalities will provide the practicing surgeon the most up-to-date algorithms for the management of his/her patient. CONCLUSIONS: The author provides a comprehensive analysis of the multidisciplinary approach to the management of carcinoma of the breast. It emphasizes the results of previous trials and discusses future controversies and areas for study. Images Figure 1. Figure 3. Figure 4. PMID:8053734

  9. Breast Carcinoma Occurring from Chronic Granulomatous Mastitis

    PubMed Central

    Luqman, Mazlan; Shahrun Niza, Abdullah Suhaimi; Saladina Jaszle, Jasmin; Nani Harlina, Md Latar; Sellymiah, Adzman; Rohaizak, Muhammad

    2012-01-01

    Chronic granulomatous mastitis is known as a benign and relatively rare disorder that is often difficult to differentiate from breast carcinoma. We highlight the case of a 34-year-old woman who had recurrent episodes of right breast swelling and abscess for 8 years. These were proven to be chronic granulomatous mastitis by tissue biopsies on 3 different occasions. Her condition improved on similar courses of antibiotics and high-dose prednisolone. However, she subsequently developed progressive loss of vision due to an orbital tumour. She then underwent a craniotomy and left orbital decompression with excision of the tumour, which proved to be a metastatic carcinoma. A trucut biopsy of the right breast was then done and showed features consistent with an infiltrating ductal carcinoma. This case illustrates the possibility that chronic granulomatous mastitis could be a precursor for malignancy and the difficulty in differentiating one from the other. The possible mechanisms of development and the implications for future management are also discussed. PMID:22973142

  10. Invasive breast carcinoma arising in microglandular adenosis: two case reports.

    PubMed

    Choi, Jung Eun; Bae, Young Kyung

    2013-12-01

    Microglandular adenosis (MGA) is a rare benign disease that shows an infiltrative growth pattern of small glands, and it may progress to include atypia and carcinoma. Here we report two cases of breast carcinoma arising in MGA. Case 1 was a 44-year-old woman with a previous history of ductal carcinoma in situ in her right breast. During a follow-up, a 1.8 cm mass-like lesion was found in her left breast. An excisional biopsy suggested that the lesion was breast carcinoma. Case 2 was a 57-year-old woman with a 2.9 cm mass in her right breast. A core needle biopsy of the lesion suggested invasive carcinoma. Both patients underwent modified radical mastectomy with sentinel lymph node biopsy. Both tumors lacked a myoepithelial cell layer and stained positively for S-100, lysozyme, and α1-antitrypsin, which is typical of MGA. Both cases showed invasive carcinoma arising in MGA. PMID:24454466

  11. [Bone metastases in breast carcinoma].

    PubMed

    Teut, Michael; Warning, Albrecht

    2006-02-01

    The case of a 66-year-old patient with multiple osteolytic bone metastases caused by breast cancer is presented. The patient refused conventional pain therapy although she suffered from severe pain. A complementary therapy with homoeopathic high potencies, devil's-claw extract, enzymes, alendronate and orthomolecular substitution as well as physiotherapy resulted in effective pain relief over a period of 1 year. The case is discussed. PMID:16582551

  12. Inflammatory breast carcinoma treated by radical radiotherapy

    SciTech Connect

    Chu, A.M.; Wood, W.C.; Doucette, J.A.

    1980-06-01

    Sixty-two patients with localized clinical inflammatory breast carcinoma were treated with curative, radical radiotherapy doses to the breast and draining lymphatics. Fifty patients have died from disease, 7 are alive with disease, and 5 are free of disease at time of reporting, thus indicating the fulminant nature of this rare form of breast cancer. Median survival is approximately 18 months. A five-year actuarial survival and relapse-free survival of 14% and 6%, respectively, are obtained. Local and regional recurrence was noted in 43 of 62 patients (69%). Twelve patients (19%) failed in the locally irradiated area only, 31 patients (50%) failed in both local, regional, and distant sites, and 14 patients (23%) failed with distant metastases only. Due to the complex dosimetry required in the treatment of breast cancer, retrospective analysis was made of actual tumor doses delivered before 1972. The breast was oftentimes calculated to receive 20 to 35% less than the stated dose. Doses in excess of 6000 rads tumor dose seem necessary since 14 of the 15 patients with persistent disesase had received less than this dose. However, once tumor exceeded 10 cm increasing dose within clinical therapeutic ranges failed to control disease, although the recurrence-free interval was somewhat prolonged. Since 1976, twice-a-day fractionation has been used in larger tumors, and this appears to have decreased the local recurrence rate to 33% (2/6) patients. Preliminary results of adjuvant multiple drug therapy appear encouraging.

  13. [Clinical problems of the breast carcinoma in situ].

    PubMed

    Börner, P; Heidenreich, W; Majewski, A

    1976-11-01

    A report of carcinoma in situ of the breast, including problems of diagnosis and treatment. Over a 6-year period cut of a total of 743 carcinomas of the breast, 77 carcinomas in situ were observed. The difficulties of diagnosis are reviewed. Treatment consisted of simple mastectomy. In view of the inadequate therapeutic results it is recommended that a modified radical mastectomy should also be done in all cases of carcinoma in situ of the breast. The pros and cons of postoperative radiation are discussed. PMID:991684

  14. 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

  15. Impact of Squamous Differentiation in Breast Carcinoma.

    PubMed

    Pai, Trupti; Shet, Tanuja; Desai, Sangeeta; Patil, Asawari; Nair, Nita; Parmar, Vani; Gupta, Sudeep; Budrukkar, Ashwini; Sarin, Rajiv; Badwe, Rajendra

    2016-09-01

    This study attempted to review the impact of extent of squamous differentiation in 56 infiltrating duct carcinomas (IDC) with squamous differentiation (metaplastic squamous carcinomas [MSC]). Tumors showing 100% squamous elements were labeled as primary squamous carcinomas (PSC; n = 28) and compared with 28 MSC showing lesser squamous components. A clinicopathological comparison revealed that lymphovascular emboli were never seen in any PSC but were noted in 7/28 of other MSC, while perineural invasion was seen only in PSC and not in MSC. Nodal metastasis was significantly more in other MSC as opposed to PSC. Most MSC presented with 2- to 5-cm sized tumors while PSC were 5 to 10 cm in size. PSC showed cystic change while MSC did not. Disease free survival (DFS) for MSC versus PSC was 64% versus 39.8%, while overall survival (OAS) was 72.7% in MSC versus 66.7% in PSC. Tumor stage affected DFS in MSC while none of the factors affected DFS/OAS in PSC. The extent of squamous differentiation affected DFS with best behavior for metaplastic carcinomas showing <40% squamous elements and worse for those with >90% squamous component (P = .024). PSC of breast is an aggressive disease and show distinct clinicopathological features from other MSC, and though the current definition of MSC does not advocate quantifying the squamous element, clearly this affects prognosis. PMID:27076454

  16. Eps8 vaccine exerts prophylactic antitumor effects in a murine model: a novel vaccine for breast carcinoma.

    PubMed

    He, Yan-Jie; Zhou, Jing; Zhao, Tong-Feng; Hu, Liang-Shan; Gan, Jing-Ying; Deng, Lan; Li, Yuhua

    2013-08-01

    Cancer vaccines are an effective way to prevent the occurrence of cancer. Epidermal growth factor receptor pathway substrate 8 (Eps8) is a novel tumor-associated antigen, which is overexpressed in the majority of tumor types. In the present study, the Eps8 protein was cloned and characterized, and its feasibility as an antitumor agent in murine breast carcinoma was investigated. The results revealed that the Eps8 protein increased the secretion of interleukin (IL)-12 in the culture supernatant of dendritic cells (DCs). The Eps8 protein‑pulsed DCs induced significant cytotoxic T lymphocyte (CTL) responses, T-cell proliferation and a higher level of interferon (IFN)-γ in the culture supernatant of the splenocytes ex vivo. Additionally, when the mice were immunized with the Eps8 vaccine, this resulted in a regression of 4T1 breast tumors and significantly prolonged survival time in the tumor‑bearing mice compared with that in the phosphate-buffered saline (PBS) control group. The Eps8 vaccine induced higher CTL responses in the splenocytes of mice vaccinated against the 4T1 cells; the ratio of CD4+/CD8+ T cells was increased in the Eps8 group; and the percentage of CD4+CD25+ FoxP3+ regulatory T (Treg) cells in the Eps8 group was significantly lower compared with that of the PBS group. The results suggested that the Eps8 vaccine was able to stimulate antitumor effects against 4T1 breast cancer cells in vitro and in vivo, and it may provide a potential immunotherapeutic agent for the treatment of breast cancer. PMID:23754615

  17. Silibinin and Paclitaxel Cotreatment Significantly Suppress the Activity and Lung Metastasis of Triple Negative 4T1 Mammary Tumor Cell in Mice

    PubMed Central

    Ho, Bing-Ying; Lin, Chun-Hung; Apaya, Maria Karmella; Chao, Wen-Wan; Shyur, Lie-Fen

    2012-01-01

    The in vitro and in vivo bioactivities of silibinin (SB), paclitaxel (PTX) and SB and PTX in combination (SB+PTX) against murine metastatic mammary 4T1 cancer cell line were investigated. Isobologram and combination index (CI) analyses showed that SB and PTX can function synergistically in the inhibition of 4T1 cell proliferation with a CI value < 1. Both SB and PTX alone or SB+PTX treatment inhibited 4T1 cell migration and motility possibly through downregulation of the serpin protease nexin-1 (PN-1) and N-cadherin expression, inhibition of matrix metalloprotease (MMP)-9 activity, and upregulation of E-cadherin. Flow cytometry and Western blot analyses demonstrated that both drugs deregulated cell-cycle mediators and induced apoptosis in 4T1 cells. A real-time in vivo bioluminescence imaging system to monitor the breast cancer cell metastasis in syngeneic BALB/c mice was established using a stable 4T1pGL-COX-2/Luc cell clone carrying a COX-2 promoter driven-luciferase reporter gene. In vivo study using the allograft 4T1pGL-COX-2/Luc metastatic mouse model indicated that SB co-treated with PTX can significantly suppress lung metastasis of 4T1 cells likely through inhibiting cell proliferation and angiogenesis. Together, this study demonstrates that SB could act synergistically with PTX in 4T1 cells, providing a therapeutic option for highly metastatic triple negative breast cancer. PMID:24716145

  18. Invasive lobular carcinoma: a rare presentation in the male breast.

    PubMed

    Melo Abreu, Elisa; Pereira, Pedro; Marques, José Carlos; Esteves, Gonçalo

    2016-01-01

    Breast cancer in men is uncommon, accounting for <1% of all breast cancers. Even though lobular structures are quite infrequent in the male breast, rare cases of invasive lobular breast carcinoma have been described, representing 1-2% of all breast cancers in men. Risk factors include undescended testes, congenital inguinal hernia, orchiectomy, orchitis, testicular injury, infertility and Klinefelter's syndrome, previous thoracic radiotherapy, alterations of the oestrogen-testosterone ratio and familial history (BRCA 2 and 1). The authors present a case of a 52-year-old man with no relevant predisposing factors to breast cancer, who presented with a painless, firm nodule, fixed to the nipple on the left breast, associated with nipple retraction and ulceration, and fully characterised by mammogram and ultrasound. Histopathological and immunohistochemical analysis revealed the diagnosis of invasive lobular breast carcinoma and the patient underwent left radical mastectomy, followed by adjuvant chemotherapy, radiotherapy and hormonotherapy. A brief review of the literature is presented. PMID:27151060

  19. GATA-3 and FOXA1 expression is useful to differentiate breast carcinoma from other carcinomas.

    PubMed

    Davis, Drew G; Siddiqui, Momin T; Oprea-Ilies, Gabriela; Stevens, Keith; Osunkoya, Adeboye O; Cohen, Cynthia; Li, Xiaoxian Bill

    2016-01-01

    GATA-3, a member of the GATA family of zinc-finger DNA binding proteins, and FOXA1, a member of the forkhead transcription factor family, are both associated with estrogen receptor expression. Both GATA-3 and FOXA1 are useful markers for breast carcinoma, but their expression in the different breast cancer subtypes and other neoplasms has not been thoroughly evaluated. We examined the expression of GATA-3 and FOXA1 in estrogen receptor-positive, Her2/neu-positive, and triple-negative breast carcinomas as well as in 10 other common carcinomas, including hepatocellular, colonic, pancreatic, gastric, endometrial (endometrioid), lung, prostatic, renal cell, urothelial, and ovarian serous carcinomas. Primary and metastatic melanomas and mesotheliomas were also evaluated. GATA-3 and FOXA1 staining of estrogen receptor-positive breast carcinomas was seen in 96.6% and 96.2%, respectively. In triple-negative breast carcinomas, GATA-3 and FOXA1 staining was seen in 21.6% and 15.9%, respectively. Among the other tumors, GATA-3 staining was only seen in urothelial carcinoma (70.9%) and FOXA1 staining was only seen in prostatic (87.5%), urothelial (5.1%) carcinomas, and mesotheliomas (40.0%). In conclusion, GATA-3 and FOXA1 are excellent breast carcinoma markers; however, their utility is limited in the triple-negative subtype. The utility of FOXA1 in diagnosing prostatic carcinoma and mesothelioma warrants further investigation. PMID:26527523

  20. The role of GATA3 in breast carcinomas: a review.

    PubMed

    Asch-Kendrick, Rebecca; Cimino-Mathews, Ashley

    2016-02-01

    GATA3 is a zinc-binding transcription factor that regulates the differentiation of many human tissue types, including the mammary gland. In surgical pathology, immunohistochemistry for GATA3 is largely used to support urothelial or breast origin in a carcinoma of unknown origin. GATA3 is sensitive but not entirely specific in this setting. Although GATA3 labeling is highest in estrogen receptor-positive carcinomas, it also labels estrogen receptor-negative carcinomas and thus has particular diagnostic utility in the setting of triple-negative breast carcinomas, which are typically negative for other mammary-specific markers. PMID:26772397

  1. Intracystic papillary carcinoma associated with ductal carcinoma in situ in a male breast: a case report

    PubMed Central

    El M’rabet, Fatema Zahra; Akesbi, Yusra; Benbrahim, Zineb; El Hind, fatemi; Znati, Kawtar; Benlemlih, Amal; Tbaili, Naima; Maaroufi, Mustapha; Tizniti, Siham; Amarti, Afaf; El Mesbahi, Omar

    2009-01-01

    Introduction Intracystic papillary carcinoma represents a small distinctive subgroup of noninvasive breast cancer, accounts for <0.5% of breast malignancies and is extremely rare in men, it was originally reported as a localized non-invasive carcinoma, but is usually associated with ductal carcinoma in situ around the main tumor or invasive carcinoma. Case presentation We report a case of 50-year-old man with intracystic papillary carcinoma in man with ductal carcinoma in situ who underwent a tumorectomy following by a radical Patey intervention (Halsted). Conclusion Nowadays, there is still no clear consensus regarding optimal treatment of intracystic papillary carcinoma. Most papers reinforce the importance of an adequate surgical margin in conservative treatment. Surgeons must pay much attention to the potential for ductal carcinoma in situ around the tumor when selecting the operative procedure. PMID:19829939

  2. Cystic carcinoma of the breast: a trap for the unwary.

    PubMed Central

    Ravichandran, D.; Carty, N. J.; al-Talib, R. K.; Rubin, C.; Royle, G. T.; Taylor, I.

    1995-01-01

    Cystic breast masses are a common presentation to breast clinics. While the majority of cysts can be managed by simple aspiration, a small proportion are malignant. Histology records for a 10-year period have been examined to identify patients with cystic breast carcinomas. In all, 31 patients were identified. Of these, 18 had cystic degeneration of high-grade tumours, while 13 had intracystic papillary carcinoma. Both of these tumour types were diagnosed by a combination of cyst fluid cytology and breast imaging. The prognosis of high-grade tumours was poor, while that of intracystic papillary carcinomas was excellent. After cyst aspiration, bloodstained fluid should be sent for cytology and breast imaging arranged in all patients. Patients in whom a cyst refills within 2 week of aspiration require a careful re-evaluation. Cysts in postmenopausal women should be viewed with suspicion. Excision should be performed in patients with positive cytology or imaging. Images Figure 1 PMID:7793801

  3. Tetrandrine Suppresses Cancer Angiogenesis and Metastasis in 4T1 Tumor Bearing Mice

    PubMed Central

    Gao, Jian-Li; He, Tong-Chuan; He, Kai; Chen, Su-Hong; Lv, Gui-Yuan

    2013-01-01

    Metastasis remains the most deadly aspect of cancer and still evades direct treatment. Thus, there is a great need to develop new treatment regimens to suppress tumor cells that have escaped surgical removal or that may have already disseminated. We have found that tetrandrine (TET) exhibits anticolon cancer activity. Here, we investigate the inhibition effect of TET to breast cancer metastasis, angiogenesis and its molecular basis underlying TET's anticancer activity. We compare TET with chemotherapy drug doxorubicin in 4T1 tumor bearing BALB/c mice model and find that TET exhibits an anticancer metastatic and antiangiogenic activities better than those of doxorubicin. The lung metastatic sites were decreased by TET, which is confirmed by bioluminescence imaging in vivo. On the other hand, laser doppler perfusion imaging (LDI) was used for measuring the blood flow of tumor in 4T1-tumor bearing mice. As a result, the local blood perfusion of tumor was markedly decreased by TET after 3 weeks. Mechanistically, TET treatment leads to a decrease in p-ERK level and an increase in NF-κB levels in HUVECs. TET also regulated metastatic and angiogenic related proteins, including vascular endothelial growth factor, hypoxia-inducible factor-1α, integrin β5, endothelial cell specific molecule-1, and intercellular adhesion molecule-1 in vivo. PMID:23762115

  4. Primary 4T1 tumor resection provides critical "window of opportunity" for immunotherapy.

    PubMed

    Ghochikyan, Anahit; Davtyan, Arpine; Hovakimyan, Armine; Davtyan, Hayk; Poghosyan, Anna; Bagaev, Alexander; Ataullakhanov, Ravshan I; Nelson, Edward L; Agadjanyan, Michael G

    2014-02-01

    It is believed that primary tumor resection modulates host-tumor immune interaction, but this has not been characterized in a stringent breast cancer tumor model. This report, using the 4T1 murine mammary tumor model, characterizes for the first time the dynamic longitudinal changes in immunosuppressive and effector components of the immune system after resection of an established orthotopic primary tumor with a defined natural history of developing lung metastases. More specifically, we analyzed changes of absolute numbers and frequencies of MDSC, regulatory T cells (Treg), as well as activated CD4 and CD8 positive T cells in spleens and, in some studies, lungs of 4T1 tumor-bearing mice and mice after primary tumor resection. Importantly, using mathematical analyses we established that primary resection of an orthotopic tumor had created a "window of opportunity" with decreased tumor-associated immune suppression that existed for approximately 10 days. Although tumor resection did slightly prolong survival, it did not affect the ultimate development of metastatic disease since animals with resected tumors or intact primary tumors eventually died by day 47 and 43, respectively. This window of opportunity likely occurs in humans providing a rationale and parameters for integration and testing of immunotherapeutic strategies in this critical "window of opportunity" to combat the development of metastatic disease. PMID:24096737

  5. Histiocytoid breast carcinoma: a case report showing immunohistochemical profiles.

    PubMed

    Li, Peifeng; Zheng, Jinfeng; Zhang, Tingguo; Cao, Ruixue; Chen, Xin; Geng, Ming

    2013-01-01

    Histiocytoid breast carcinoma (HBC) is a rare type of breast cancer with a controversial histogenesis. Here we describe a case report of a 65-year old woman with HBC. The patient presented with two masses in the right breast. Histopathologically, the tumors consisted of a diffuse infiltration of large tumor cells and histological components of carcinoma in situ and atypical lobular hyperplasia were also observed. The infiltration pattern was similar to that of invasive lobular carcinoma with targetoid and Indian file arrangements. The invasive histiocytoid cells had finely granular, eosinophilic to vesicular cytoplasm and nuclei with a bland uniform appearance, a single small eosinophilic nucleolus and finely granular chromatin. We compared the immunohistochemical profiles of 17 breast cancer markers between invasive carcinoma, carcinoma in situ, atypical lobular hyperplasia and normal breast epithelium. Although they all shared the same reactivity for many of the proteins, they exhibited differences in GCDFP-15, E-cadherin, P120, CEA, HER-2, ER and PR expression, and these are discussed. This is the first case study of two HBC masses occurring in one breast simultaneously. By analyzing and comparing their morphologic characteristics and spectrum of immunohistochemical expression, our study supports the view that HBC is a variant of lobular carcinoma and our findings may assist in future diagnoses of HBC. PMID:24228128

  6. Targeted Glycoproteomic Identification of Biomarkers for Human Breast Carcinoma

    PubMed Central

    Abbott, Karen L.; Aoki, Kazuhiro; Lim, Jae-Min; Porterfield, Mindy; Johnson, Rachelle; O’Regan, Ruth M.; Wells, Lance; Tiemeyer, Michael; Pierce, Michael

    2016-01-01

    Glycosylation is a dynamic post-translational modification that changes during the development and progression of various malignancies. During the oncogenesis of breast carcinoma, the glycosyltransferase known as N-acetylglucosaminyltransferase Va (GnT-Va) transcript levels and activity are increased due to activated oncogenic signaling pathways. Elevated GnT-V levels leads to increased β(1,6)-branched N-linked glycan structures on glycoproteins that can be measured using a specific carbohydrate binding protein or lectin known as L-PHA. L-PHA does not bind to nondiseased breast epithelial cells, but during the progression to invasive carcinoma, cells show a progressive increase in L-PHA binding. We have developed a procedure for intact protein L-PHA-affinity enrichment, followed by nanospray ionization mass spectrometry (NSI-MS/MS), to identify potential biomarkers for breast carcinoma. We identified L-PHA reactive glycoproteins from matched normal (nondiseased) and malignant tissue isolated from patients with invasive ductal breast carcinoma. Comparison analysis of the data identified 34 proteins that were enriched by L-PHA fractionation in tumor relative to normal tissue for at least 2 cases of ductal invasive breast carcinoma. Of these 34 L-PHA tumor enriched proteins, 12 are common to all 4 matched cases analyzed. These results indicate that lectin enrichment strategies targeting a particular glycan change associated with malignancy can be an effective method of identifying potential biomarkers for breast carcinoma. PMID:18271524

  7. Multimodal therapy in locally advanced breast carcinoma

    SciTech Connect

    Lopez, M.J.; Andriole, D.P.; Kraybill, W.G.; Khojasteh, A. )

    1990-12-01

    Among 879 patients treated for breast cancer between 1975 and 1984, advanced disease was found in 125 (14%). A subgroup of 34 (4%) presented with untreated locally advanced disease without demonstrable distant metastases at the time of diagnosis (stage IIIB = T4abed, NX-2,MO). During the first 5 years (1975 through 1979), 17 patients were treated primarily with sequential radiotherapy and chemotherapy (Group A). From 1980 to 1984 (Group B), the management consisted of four courses of induction multi-drug chemotherapy followed primarily by mastectomy and additional chemotherapy. The mean follow-up for the most recent group (Group B) is 48 months. Follow-up was complete. While the local disease control rate was the same for both groups (76%), the survival was remarkably different. Group A patients experienced a median survival of 15 months, and only one survived 5 years. In Group B, the median survival was 56 months with nine patients (53%) alive between 40 and 76 months, seven (41%) of whom are 5-year survivors. While the overall mortality of patients with inflammatory breast cancer was greater in both groups when compared with the group with noninflammatory disease, the survival of patients in Group B was better than in Group A for both inflammatory and noninflammatory cancers (p less than 0.01). Estrogen receptor, nodal, and menopausal status did not influence survival. These data suggest that neoadjuvant chemotherapy improves survival for patients with stage IIIB breast carcinoma and delays the establishment or progression of distant metastases. Mastectomy is an important component in the treatment of this disease.

  8. Rapid onset of cutaneous angiosarcoma after radiotherapy for breast carcinoma

    SciTech Connect

    Otis, C.N.; Peschel, R.; McKhann, C.; Merino, M.J.; Duray, P.H.

    1986-06-01

    Malignant neoplasms known to develop following external beam radiation include squamous cell carcinoma, osteosarcoma, chondrosarcoma, malignant fibrous histiocytoma, mixed mullerian tumors, malignant schwannoma, myelogenous leukemia and angiosarcoma. Latency periods of many years characterize the onset of these tumors following the exposure. Cutaneous angiosarcoma following radiotherapy for breast carcinoma has been rarely documented, occurring up to 13 years postirradiation. Two cases of this entity are reported occurring 37 months postradiotherapy at the site of mastectomy performed for mammary duct carcinoma.

  9. Acinic cell carcinoma of breast: morphologic and immunohistochemical review of a rare breast cancer subtype.

    PubMed

    Conlon, Niamh; Sadri, Navid; Corben, Adriana D; Tan, Lee K

    2016-05-01

    Acinic cell carcinoma of breast is a rare subtype of triple-negative breast carcinoma and demonstrates extensive morphologic overlap with acinic cell carcinoma of the salivary gland. In this study, we perform a detailed morphologic and immunohistochemical description of 2 cases of this rare entity and undertake a comprehensive review of all reported cases of breast acinic cell carcinoma in the English language literature to date. One-third of reported cases of breast acinic cell carcinoma have been associated with the presence of a ductal carcinoma not otherwise specified component, which is frequently poorly differentiated. Breast acinic cell carcinoma can demonstrate focal morphologic features similar to microglandular adenosis; these areas are frequently negative for collagen IV and laminin on immunohistochemistry. The true relationship between these 2 entities remains unclear, but we advocate that microglandular adenosis-like areas at the periphery of a breast acinic cell carcinoma should be considered part of the carcinomatous process and re-excised if this process extends to the initial surgical margins. PMID:27067778

  10. Cutaneous metastasis of breast adenoid cystic carcinoma to the scalp.

    PubMed

    Little, Anthony J; Seline, Alison E; Swick, Brian L; Wanat, Karolyn A

    2016-08-01

    Adenoid cystic carcinoma (ACC) is a tumor that can be of primary cutaneous origin or secondary to metastatic disease, most commonly salivary origin. Aside from primary cutaneous and salivary types, ACC of the breast is a rare, more indolent variant. Cutaneous metastases secondary to breast ACC is exceedingly uncommon and not previously reported to our knowledge. We present the case of a 67-year-old woman who developed cutaneous metastasis from primary breast ACC. PMID:26968987

  11. Intracystic papillary breast carcinoma with areas of infiltration

    PubMed Central

    Martín Gutiérrez, Silvia; Nieto Gallo, María Antonia; Noguero Meseguera, Rosario; Rodríguez Prieto, Ignacio

    2012-01-01

    Intracystic papillary carcinoma of the breast associated with areas of infiltration is rare in that it constitutes less than 1% of breast cancers. After initial radiological study, these tumors show lesions with little likelihood of malignancy in a high proportion of cases. Two cases of intracystic papillary carcinoma associated with infiltration were diagnosed at the Breast Unit of Hospital Infanta Cristina. In both cases, the reason for consultation arose after palpation of a nodule and the initial radiographic analyses showed lesions with little likelihood of malignancy. PMID:24893058

  12. [Studies on the location of eight lectins in breast carcinoma].

    PubMed

    Zheng, Z; Ji, Z M

    1990-12-01

    100 cases of breast carcinoma were studied with lectin affinitive histochemistry technology. The result showed that Ricinus comunis agglutinin (RCA1) was located in almost all intraductal carcinomas but one, while the positive rates in the other types were obviously low (P less than 0.05). The positive rate of Ulex europaeus agglutinin-I (UEA1) in well-differentiated types was higher than that in poorly-differentiated ones (P less than 0.05). The location of Peanut agglutinin (PNA), Bandeiraea Simplicifolia (BSL) and UEA1 in breast carcinomas exhibited some regularity and it might be useful in understanding the differentiation of breast carcinomas. No relationship between changes of the eight lectins and metastases in axillary lymph nodes was observed, but the authors considered that PNA-affinitive histochemistry was beneficial to the detection of micrometastases in lymph nodes. PMID:1964401

  13. Metastatic gastrinoma in the breast mimicking primary solid papillary carcinoma.

    PubMed

    Burt, Michael; Madan, Rashna; Fan, Fang

    2016-10-01

    We report a case of metastatic gastrinoma to the breast morphologically mimicking solid papillary carcinoma of the breast. A 59-year-old woman presented with a hypoechoic right breast mass that histologically revealed solid nests of small monotonous tumor cells, fibrovascular cores, and round to oval nuclei with fine chromatin and small nucleoli. Immunohistochemistry demonstrated chromogranin and synaptophysin positivity. Tumor prognostic markers showed weak positivity for estrogen receptor and negativity for progesterone receptor. Although an initial diagnosis of solid papillary carcinoma was rendered, subsequent identification of the patient's clinical history of pancreatic gastrinoma and an additional immunohistochemical stain for gastrin supported a diagnosis of metastatic gastrinoma. We report this rare case to increase awareness of metastatic neuroendocrine tumors in the breast. Multiple breast lesions and lack of expression of estrogen/progesterone hormone receptors should prompt careful review of the patient's clinical history to rule out metastatic neuroendocrine disease. PMID:27342908

  14. Infiltrating ductal carcinoma of the breast associated with primary breast lymphoma.

    PubMed

    Arlen, Myron; Freiman, Jacob J; Ionescu, Marina

    2011-01-01

    We report on the development of an uncommon association of pathologic processes, where an invasive adenocarcinoma of the breast developed concomitantly with a primary lymphoma arising in the same breast. The patient, a 78 year old female, presented with two palpable breast lesions in her left breast and an additional lesion in the right breast. Core needle biopsies of the lesions revealed both ductal carcinoma and lymphoma existing adjacent to each other in the left breast and a second primary lymphoma in her right breast. The mammogram, which also defined the lesions, illustrated collision tumors of the left breast and a separate pathologic process in the right breast. Excision of the lesions confirmed the two independent lesions on the left side, one an infiltrating ductal carcinoma and the second a large B-cell lymphoma. Biopsy of the right breast also demonstrated existence of a large B-cell lymphoma. Left axillary biopsy using sentinel node technology indicated that there was no evidence of nodal metastasis. The question arose as to possible etiologic factors related to viral transfection at the DNA level, that could cause transformation within the ductal epithelium of the breast with similar transfection of the lymphocytes of an adjacent intramammary node, that led to the development of the simultaneous pathologic processes of ductal carcinoma and B-cell lymphoma, defined on biopsy. PMID:21475637

  15. Genomic landscape of small cell carcinoma of the breast contrasted to small cell carcinoma of the lung.

    PubMed

    McCullar, Brennan; Pandey, Manjari; Yaghmour, George; Hare, Felicia; Patel, Kruti; Stein, Matthew; Feldman, Rebecca; Chandler, Jason C; Martin, Michael G

    2016-07-01

    Small cell carcinoma of the breast is a rare, aggressive form of breast cancer that is associated with extremely poor outcomes [1]. In an effort to identify possible targets for treatment, we utilized comprehensive genomic profiling in small cell carcinoma of the breast. Under an IRB approved protocol, we identified patients with small cell carcinoma of the breast and small cell carcinoma of the lung profiled by Caris Life Sciences between 2007 and 2015. Tumors were assessed with up to 25 immunohistochemical stains, in situ hybridization of cMET, EGFR, HER2, PIK3CA, and TOP2A, and next generation sequencing as well as Sanger sequencing of 47 genes. 19 patients with small cell carcinoma of the breast were identified, median age was 58 years (range 37-79) and 42 % had metastatic disease at presentation; for comparison, 58 patients with small cell carcinoma of the lung were identified (66 [36-86], 65 % metastatic). By immunohistochemistry, 31 % of small cell carcinoma of the breast patients expressed ER, 13 % expressed PR, and 16 % expressed AR; small cell carcinoma of the lung patients expressed ER 0 %, PR 2 %, and AR 6 %. Small cell carcinoma of the breast and small cell carcinoma of the lung patients had similar patterns of other immunohistochemical expression (0 v 0 % PDL1, 50 v 42 % PD1, and 77 v 95 % TOP2A, respectively). All small carcinoma of the breast and small cell carcinoma of the lung patients were negative for HER2 and cMET amplification by in situ hybridization. Next generation sequencing revealed TP53 mutations in 75 % of patients both with small cell carcinoma of the breast and small cell carcinoma of the lung and PIK3CA mutations in 33 % of small cell carcinoma of the breast patients but no small cell carcinoma of the lung patients (Fisher's exact test p = 0.005, OR 0.02 [0.00-0.52]). No other mutations were found in small cell carcinoma of the breast patients and no other mutation occurred in over 10 % of small cell carcinoma of the

  16. Autoantibodies to tumor-associated antigens in breast carcinoma.

    PubMed

    Piura, Ettie; Piura, Benjamin

    2010-01-01

    Autoantibodies (AAbs) to tumor-associated antigens (TAAs) have been identified in the circulation of patients with cancer. This paper will focus on recent knowledge related to circulating AAbs to TAAs in breast carcinoma. So far, the following TAAs have been identified to elicit circulating AAbs in breast carcinoma: p53, MUC-1, heat shock proteins (HSP-27, HSP-60, and HSP-90), HER2/neu/c-erb B2, GIPC-1, c-myc, c-myb, cancer-testis antigens (NY-ESO-1), BRCA1, BRCA2, endostatin, lipophilin B, cyclin B1, cyclin D1, fibulin, insulin-like growth factor binding protein 2 (IGFBP-2), topoisomerase II alpha (TOPO2α), and cathepsin D. Measurement of serum AAbs to one specific TAA only is of little value for screening and early diagnosis of breast carcinoma; however, assessment of AAbs to a panel of TAAs may have promising diagnostic potential. PMID:21113302

  17. Immunophenotypic and genomic characterisation of papillary carcinomas of the breast

    PubMed Central

    Lacroix-Triki, Magali; Lambros, Maryou B; MacKay, Alan; A’Hern, Roger; Gauthier, Arnaud; Pawar, Vidya; Colombo, Pierre-Emanuel; Daley, Frances; Natrajan, Rachael; Ward, Eric; MacGrogan, Gaëtan; Arbion, Flavie; Michenet, Patrick; Weigelt, Britta; Vincent-Salomon, Anne; Reis-Filho, Jorge S

    2016-01-01

    Papillary carcinomas are a special histological type of breast cancer, and have a relatively good outcome. We characterised the genomic and phenotypic characteristics of papillary carcinomas, and to determine whether they would constitute an entity distinct from grade- and oestrogen receptor (ER)-matched invasive ductal carcinomas of no special type (IDC-NSTs). The phenotype of 63 papillary carcinomas of the breast and grade- and ER-matched IDC-NSTs was determined by immunohistochemistry. DNA of sufficient quality was extracted from 49 microdissected papillary carcinomas and 49 microdissected grade- and ER-matched IDC-NSTs. These samples were subjected to high-resolution microarray-based comparative genomic hybridisation (aCGH) and MassARRAY Sequenom sequencing analysis of 19 known oncogenes. Papillary carcinomas were predominantly of low histological grade, expressed immunohistochemical markers consistent with a luminal phenotype, and a lower rate of lymph node metastasis and p53 expression than grade- and ER-matched IDC-NSTs. Papillary carcinomas displayed less genomic aberrations than grade- and ER-matched IDC-NSTs; however the patterns of gene copy number aberrations found in papillary carcinomas were similar to those of ER- and grade-matched IDC-NSTs, including 16q losses. Furthermore, PIK3CA mutations were found in 43% and 29% of papillary carcinomas and grade- and ER-matched IDC-NSTs respectively. The genomic profiles of encapsulated, solid and invasive papillary carcinomas, the three morphological subtypes, were remarkably similar. Our results demonstrate that papillary carcinomas are a homogeneous special histological type of breast cancer. The similarities in the genomic profiles of papillary carcinomas and grade- and ER-matched IDC-NSTs suggest that papillary carcinomas may be best positioned as part of the spectrum of ER-positive breast cancers rather than as a distinct entity. Furthermore, the good prognosis of papillary carcinomas may stem from the

  18. Metastatic metaplastic breast carcinoma mimicking pulmonary squamous cell carcinoma on fine-needle aspiration.

    PubMed

    Nguyen, Doreen N; Kawamoto, Satomi; Cimino-Mathews, Ashley; Illei, Peter B; Rosenthal, Dorothy L; VandenBussche, Christopher J

    2015-10-01

    Metaplastic squamous cell carcinoma (SCC) of the breast is a rare type of breast cancer. Metastases to the lung, which can be a major site of second primary tumor development among breast cancer patients, are difficult to distinguish from primary SCC of the lung and present a unique challenge for pathologists. There are few available discriminating immunohistochemical markers as squamous differentiation typically leads to loss of expression of characteristic primary epithelial cell markers of both breast and lung origin. GATA protein binding 3 (GATA-3) is a useful marker of breast origin in metastatic ductal and lobular carcinomas including poorly differentiated triple-negative carcinomas and some metaplastic carcinomas. Here, we present a case of metastatic SCC presenting as a solitary lung mass with regional lymph node metastases and a single satellite lesion in a patient with a history of metaplastic SCC of the breast. In addition to the routine markers of squamous differentiation, the metastases were also positive for estrogen receptor (ER) and GATA-3 on cytologic material obtained by transbronchial FNA. This suggests that immunoreactivity for ER and GATA-3 may support a diagnosis of metastatic SCC in the context of a prior metaplastic SCC of the breast. PMID:26238413

  19. Expression of oestrogen receptor alpha variants in non-malignant breast and early invasive breast carcinomas.

    PubMed

    Chappell, S A; Johnson, S M; Shaw, J A; Walker, R A

    2000-10-01

    Oestrogen receptor (ER) alpha variants have been described in normal breast and breast carcinomas, but their presence in a range of benign conditions and in small early invasive breast carcinomas has not been considered. Cryostat tissue sections from 19 normal and proliferative breast lesions and 44 carcinomas 15 mm and less in size detected by mammographic screening were screened for ERalpha splice variants using reverse transcriptase-nested PCR. The carcinomas were assessed for mutation by single-stranded conformational polymorphism analysis and variant forms/band shifts were sequenced. ERalpha was detected in all 19 non-malignant cases and exon 7-deleted variants were found in 16 of them. Three cases showed weak expression of exon 5, and two of exon 3 variants. There was no relationship between the presence of variants and the extent of proliferative change, ER status or age. ERalpha mRNA was not detected in two carcinomas; exon 3 deletions were found in four (9. 5%) of the other carcinomas, exon 5 in two (4.8%), and exon 7 in 11 (26.2%), with two variants in four carcinomas and a total of 29.5% of all cases having detectable variants. Two point mutations were found in one, which was a tubular carcinoma. Variant forms were identified in carcinomas of all sizes (bar<10 mm) but were more frequent in those of 15 mm. There was no relationship with type, grade or receptor status. The main difference between non-malignant breast and early invasive cancers related to exons 3 and 5. The findings suggest that ERalpha variants are not involved in breast cancer development but occur with tumour progression and may be a consequence rather than a cause. PMID:11004691

  20. Breast carcinoma in a boy with metastatic axillary lymph nodes

    PubMed Central

    Hamza, Aamir A; Ngwangki, Lodu S; Taha, Osman

    2012-01-01

    The purpose of this report is to highlight the clinicopathological features, diagnosis, management and prognosis of rare childhood breast cancer. We herein report a case of slowly growing, locally advanced secretory carcinoma of the breast in an 11-year-old boy with metastatic axillary lymph nodes, 12 of them were totally replaced by the tumor cells. No evidence of distant metastases was detected. Modified radical mastectomy with axillary clearance was done, with uneventful postoperative course. On searching the Sudan medical literature, no previous report of similar case was found. In conclusion, breast carcinoma, though a rare entity, yet should be borne in mind if a firm breast lump was found in a child. Fine needle aspiration cytology is effective to start with as a diagnostic tool.

  1. SMAD4 expression in breast ductal carcinoma correlates with prognosis

    PubMed Central

    LIU, NANNAN; YU, CHUNYAN; SHI, YANFEN; JIANG, JING; LIU, YUHE

    2015-01-01

    The present study examined SMAD4 expression in fine-needle aspiration cell blocks from patients with breast ductal carcinoma, in order to assess its viability as a prognostic marker. Using immunohistochemistry, the SMAD4 protein status of 86 breast ductal carcinoma fine-needle biopsies, from patients who underwent tumor resection at Beihua University Affiliated Hospital (Jilin, China) between 2002 and 2008, was characterized. The association between SMAD4 expression and clinicopathological parameters, as well as prognosis was assessed using the Mantel-Haenszel method and Cox proportional hazards regression. SMAD4 staining was observed in the cytoplasm and nucleus, and its expression was found to be decreased in ductal breast carcinoma as compared with adjacent normal breast epithelia. Patients with reduced SMAD4 expression levels tended to exhibit more poorly differentiated tumors, a higher risk of recurrence and shorter overall survival. These results demonstrated that the evaluation of SMAD4 protein status in fine-needle biopsy specimens of breast ductal carcinoma may provide additional prognostic information. PMID:26622737

  2. Pigmented papillary carcinoma: a rare tumor of the male breast.

    PubMed

    Farkas, Andrea; Istók, Roland; Székely, Eszter; Glasz, Tibor; Kulka, Janina

    2008-09-01

    Primary melanin pigment containing tumors of the breast are rare. We report a pigmented papillary carcinoma of a 60-year-old male patient who presented a firm mass 1.7 cm in diameter with an ill defined border on ultrasonography behind the mamilla. To the best of our knowledge this is the third case report of this type of tumor in male breast. PMID:18575825

  3. Intracystic Papillary Carcinoma of the Breast in a Male Patient

    PubMed Central

    Hu, Zishuo Ian; Liu, Chengbao; Fisher, Paul R.; Cohen, Jules A.

    2016-01-01

    We report a case of intracystic papillary carcinoma of the right breast in a 59-year old man presenting with bloody nipple discharge for 1 week prior to presentation. Mammography, ultrasonography, and core needle aspiration were consistent with intracystic papillary carcinoma. The patient underwent right simple mastectomy. Pathology was also consistent with low grade intracystic papillary carcinoma. The 21-gene assay revealed a recurrence score of 0, corresponding to a 3% risk of distant recurrence at 10 years. A patient did not receive chemotherapy or post-mastectomy radiotherapy. The patient was placed on tamoxifen and has been free of disease to date. PMID:27134706

  4. Invasive ductal carcinoma arising from dense accessory breast visualized with 99mTc-MIBI breast-specific γ imaging.

    PubMed

    Yoon, Hai-Jeon; Sung, Sun Hee; Moon, Byung In; Kim, Bom Sahn

    2014-08-01

    Primary accessory breast cancer is extremely rare, and the diagnostic efficacy of Tc-MIBI breast-specific γ imaging (BSGI) has not been reported elsewhere. We present a case of primary carcinoma arising from dense accessory breast that was visualized with BSGI. A 43-year-old female patient with a palpable axillary mass underwent mammography, which showed dense parenchyma on both of the anatomic and accessory breasts with no abnormality. Subsequent BSGI showed no abnormal uptake in bilateral anatomic breasts, but focal abnormal uptake was noted in the accessory breast. Permanent pathologic evaluation confirmed invasive ductal carcinoma (not otherwise specified type) of the accessory breast. PMID:24445272

  5. Novel Use for DOG1 in Discriminating Breast Invasive Carcinoma from Noninvasive Breast Lesions

    PubMed Central

    Cheng, Henghui; Qu, Zhiling; Zhou, Sheng; Ruan, Qiurong

    2016-01-01

    Aims. DOG1 has proven to be a useful marker of gastrointestinal stromal tumors (GISTs). Recently, DOG1 expression has also been reported in some non-GIST malignant tumors, but the details related to DOG1 expression in breast tissue remain unclear. The aim of this study was to detect the expression of DOG1 in the human breast and to evaluate the feasibility of using DOG1 to discriminate between invasive breast carcinoma and noninvasive breast lesions. Methods and Results. A total of 210 cases, including both invasive and noninvasive breast lesions, were collected to assess DOG1 expression immunohistochemically. DOG1 expression was consistently positive in breast myoepithelial cells (MECs), which was similar to the results obtained for three other MEC markers: calponin, smooth muscle myosin heavy chain (SMMHC), and P63 (P > 0.05 in all). Importantly, DOG1 was useful in discriminating invasive breast carcinoma from noninvasive breast lesions (P < 0.05). Conclusions. DOG1 is a useful marker of breast MECs, and adding DOG1 to the MEC identification panel will provide more sophisticated information when diagnosing uncertain cases in the breast. PMID:27041791

  6. Palmar dermatoglyphics in carcinoma breast of Indian women.

    PubMed

    Sridevi, N S; Delphine Silvia, C R Wilma; Kulkarni, Roopa; Seshagiri, C

    2010-01-01

    The present study was planned to assess the relationship of palmar dermatoglyphic patterns of hands in women with breast cancer and or at risk for developing breast cancer. This study was conducted on 100 histopathologically confirmed breast cancer patients in women and their digital dermatoglyphic patterns were studied to assess their association with the type and onset of breast cancer. Simultaneously 100 age-matched controls were also selected with no self or familial history of a diagnosed breast cancer and the observations were recorded. The differences of qualitative (dermatoglyphic patterns) data were tested for their significance using the chi-square test, and Student's t-test was used for quantitative (ridge counts and pattern intensity index) data analysis. The results of the study indicated statistically significant changes in finger ridge count and fingertip pattern in cases of carcinoma breast as compared to the control group. Palmar dermatoglyphics is simple, inexpensive, anatomical and non-invasive and may be used as a reliable indicator for screening of high-risk population in developing country like India, for early detection and early therapy, thus reducing the morbidity and mortality in cases of carcinoma breast. PMID:20809035

  7. BRCA1 mutations in primary breast and ovarian carcinomas

    SciTech Connect

    Futreal, P.A.; Cochran, C.; Bennett, L.M.; Haugen-Strano, A.; Terry, L.; Barrett, J.C.; Wiseman, R.; Liu, Q.; Shattuck-Eidens, D.; Harshman, K.

    1994-10-07

    Loss of heterozygosity data from familial tumors suggested that BRCA1, a gene that confers susceptibility to ovarian and early-onset breast cancer, encodes a tumor suppressor. The BRCA1 region is also subject to allelic loss in sporadic breast and ovarian cancers, an indication that BRCA1 mutations may occur somatically in these tumors. The BRCA1 coding region was examined for mutations in primary breast and ovarian tumors that show allele loss at the BRCA1 locus. Mutations were detected in 3 of 32 breast and 1 of 12 ovarian carcinomas; all four mutations were germline alterations and occurred in early-onset cancers. These results suggest that mutation of BRCA1 may not be critical in the development of the majority of breast and ovarian cancers that arise in the absence of a mutant germline allele.

  8. Biomarker signatures of mitochondrial NDUFS3 in invasive breast carcinoma

    SciTech Connect

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

    2011-09-09

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

  9. Breast Carcinoma in Young Women: No Evidence of Increasing Rates of Metastatic Breast Carcinoma in a Single Tertiary Center Review.

    PubMed

    Conlon, Niamh; Howard, Jane; Catalano, Jeffrey; Gallagher, Meighan; Tan, Lee K; Corben, Adriana D

    2016-05-01

    Breast carcinoma in young women aged less than 40 years attracts a high level of mainstream media coverage, and there is a gap between societal perceptions of the disease as a growing problem and epidemiological trends. Several population studies have reported that the overall incidence of breast carcinoma in young women is stable, while one recent article suggested that the relative proportion of breast carcinoma in young women that is metastatic at diagnosis is growing. We sought to establish whether these trends were apparent at our institution. In this study, the clinical database at a breast carcinoma tertiary center was reviewed in terms of clinicopathologic data on patient age, diagnosis, clinical and pathologic stage, hormone receptor status, and HER-2 overexpression status for the period 2000-2011. Over the study period, young patients represented a decreasing proportion of all breast carcinoma cases (10.8% [2000-2003] to 8.7% [2008-2011]; p < 0.0001) treated at our institution. Young patients were more likely than patients aged 40 years or older to present with metastatic (M1) disease (5.4% versus 4.4%; p = 0.009), to be triple negative (21.6% versus 13%; p < 0.001), or to be HER-2 positive (24.3% versus 14.8%; p < 0.01). Young patients with HER-2-positive cancers were significantly more likely to present with metastatic disease (8.3% versus 4.8%; p = 0.004). This study showed no demonstrable increase in the relative proportion of breast cancer occurring in patients aged <40 years over the 12-year period 2000-2011 and no increase in the proportion of young patients presenting with metastatic disease. PMID:26923423

  10. Differential characteristics of heart, liver, and brain metastatic subsets of murine breast carcinoma.

    PubMed

    Erin, Nuray; Kale, Sule; Tanrıöver, Gamze; Köksoy, Sadi; Duymuş, Ozlem; Korcum, Aylin F

    2013-06-01

    Breast carcinoma is comprised of heterogeneous groups of cells with different metastatic potential. To develop effective therapeutic strategies targeting metastatic disease, it is crucial to understand the characteristics of breast cancer cells that enable metastasis to distant organs. 4THM breast carcinoma cells are the cells of 4T1 primary tumors that metastasized to the heart. Cells of 4THM tumors which metastasized to liver (4TLM) were previously isolated. Recently macroscopic brain metastasis in 4THM injected animals, were isolated to obtain a brain metastatic cell line (4TBM). Using an orthotopic mouse model differential characteristic of cells metastasized to heart (4THM), liver (4TLM), and brain (4TBM) were compared for ability to metastasize and expression of stem cell markers. We found that 4TLM cells produced significantly more lung and liver metastasis compared to 4TBM and 4THM cells. In vitro, proliferation as well as migration rate of 4TLM cells was also significantly higher than the other cell lines. Remarkably primary tumors formed by 4TLM cells expressed significant amounts of CD34, a marker for mesenchymal malignancies. Markers of epithelial-mesenchymal transition were expressed in all metastatic cells, but the degree of expression differed. Majorities of 4TLM, 4THM, and 4TBM cells were CD44+ CD24- whereas, 12 % of 4TLM cells also expressed membranous CD24. Conditioned mediums of non-metastatic 67NR breast tumors and cancer-associated fibroblasts inhibited growth of highly metastatic 4TLM cells. Malignant cells metastasized to brain were distinguished by membranous E-cadherin expression that was markedly higher in 4TBM cells grown as spheroids suggesting E-cadherin is required for brain metastasis. Differential features of heart, brain, and liver metastatic cells in a syngenic model was shown in this study for the first time. These findings not only provide a model to explore new treatment modalities, but also demonstrate differential features of

  11. Breast carcinomas occurring in young women (< 35 years) are different.

    PubMed Central

    Walker, R. A.; Lees, E.; Webb, M. B.; Dearing, S. J.

    1996-01-01

    One hundred and sixty-three breast carcinomas occurring in women aged between 26 and 44 years were examined for pathological features, oestrogen and progesterone receptor status, proliferation as determined by Ki-67 labelling and the presence of c-erbB-2 and p53 protein, and were compared with a control group of carcinomas from women in the 50-67 years age group. Carcinomas occurring in women aged under 35 years had a significantly high incidence of being poorly differentiated and of having high proliferation rates. This group also had a significantly high incidence of p53 protein staining. Carcinomas in the under 30 years age group had a lower incidence of oestrogen and progesterone receptor positivity. No differences were found in c-erbB-2-positive staining between the groups. Infiltrating lobular carcinomas were only identified in women aged 40 years and over. There was a higher incidence of a family history in the 35-44 years age group (18%) than in the under 35 years age group (11%). Breast carcinomas occurring in women aged under 35 years are more aggressive. An important finding is the high incidence of p53 positivity, which may indicate genetic instability. Images Figure 1 PMID:8956795

  12. Down-regulation of laminin-5 in breast carcinoma cells.

    PubMed Central

    Martin, K. J.; Kwan, C. P.; Nagasaki, K.; Zhang, X.; O'Hare, M. J.; Kaelin, C. M.; Burgeson, R. E.; Pardee, A. B.; Sager, R.

    1998-01-01

    BACKGROUND: Laminin-5 (ln-5), a large heterotrimeric glycoprotein consisting of an alpha 3, beta 3, and gamma 2 chain, is a component of epithelial cell basement membranes that functions as a ligand of the alpha 3 beta 1 and alpha 6 beta 4 integrins to regulate cell adhesion, migration, and morphogenesis. The ln-5 chains show tissue-specific patterns of regulation in tumors derived from different tissues. For example, ln-5 is often up-regulated in gliomas, gastric carcinomas, and squamous carcinomas and down-regulated in prostate and basal cell carcinomas. Ln-5 expression patterns may represent useful tumor markers and help to elucidate the role of ln-5 in tumor progression in different tissue types. MATERIALS AND METHODS: We have studied ln-5 expression patterns in the breast. mRNA levels were examined in tumor and normal breast epithelial cell lines, tissue samples, and immunomagnetically sorted primary cultures using differential display, Northern blotting, and hybridization arrays. Protein levels were examined by immunoprecipitation. Gene integrity was assessed by Southern blotting of representative cell types. RESULTS: Ln-5 alpha 3, beta 3, and gamma 2 mRNA expression was found to be markedly down-regulated in a panel of breast tumor cell lines when compared with normal breast epithelial cells. Ln-5 mRNA was expressed at relatively high levels in MCF-10A immortal normal breast epithelial cells, long-term cultures of normal breast cells, and sorted primary cultures of normal breast luminal epithelial and myoepithelial cells. Reduced, but detectable, levels of ln-5 tended to be expressed in cell lines derived from early-stage breast tumors, whereas expression was generally not detected in cell lines derived from later-stage tumors. In breast tumor tissue specimens, expression of ln alpha 3 and beta 3 mRNAs tended to be reduced relative to levels observed in adjacent nontumor tissue, whereas in gamma 2 levels were elevated in specimens with increased amounts of

  13. Breast filariasis or inflammatory breast carcinoma? Reaching a diagnosis.

    PubMed

    Panda, Dwijesh Kumar; Mohapatra, Devi Prasad; Mohapatra, Madhusmita Mohanty

    2015-01-01

    Lymphatic filariasis is a neglected tropical disease caused by the parasite Wuchereria bancrofti. Involvement of the breast is relatively uncommon and may affect only 10% of individuals with lymphatic filariasis. We present a case of an elderly woman with breast pathology. The condition clinically appeared as a malignancy. Routine diagnostic tests including tissue histopathological studies failed to clinch a diagnosis. However, a serological test helped in identifying the pathology, which turned out to be a manifestation of breast filariasis, and aided in instituting appropriate therapy for this condition. PMID:26567240

  14. [A case of spindle cell carcinoma of the breast].

    PubMed

    Oshida, Sayuri; Hayashi, Keiko; Habiro, Takeyoshi; Nemoto, Kazuhiko; Sengoku, Norihiko; Watanabe, Masahiko

    2014-11-01

    The patient was a 53-year-old woman in whom ultrasonography of the breast revealed a lobular mass, 14 mm in diameter, in the right AB region. Spindle cells were obtained on fine-needle aspiration biopsy, but it was not possible to diagnose whether the tumor was benign or malignant. Contrast-enhanced magnetic resonance imaging showed a mass with a cystic component that was darkly stained in the early phase. Needle biopsy showed a dense proliferation of atypical spindle cells with no distinct epithelial-like arrangement. The differential diagnosis included mesenchymal malignant tumors such as fibrosarcoma, some phyllodes tumors, and epithelial tumors with sarcomatoid differentiation. Immunostaining revealed that the tumor was cytokeratin (AE1/AE3)-negative, partially CAM 5.2-positive, p63-positive, S100-negative, SMA-positive, partially vimentin-positive, with a Ki-67 index of 80% and negativity for ER, PgR, and HER2. Spindle-cell carcinoma was thus diagnosed. A partial right mastectomy with sentinel lymph-node biopsy was performed. Immunostaining of the resected specimen confirmed spindle cell carcinoma. The General Rules for Clinical and Pathological Recording of Breast Cancer classify spindle cell carcinoma as a special type of invasive cancer with a sarcomatoid structure, consisting of spindle-shaped cancer cells. This type of carcinoma is extremely rare, accounting for less than 1% of all breast cancers. PMID:25731380

  15. Conservation therapy for breast cancers other than infiltrating ductal carcinoma.

    PubMed

    Kurtz, J M; Jacquemier, J; Torhorst, J; Spitalier, J M; Amalric, R; Hünig, R; Walther, E; Harder, F; Almendral, A; Brandone, H

    1989-04-15

    Pathologic review of 861 Stage I and II breast cancers yielded 152 patients (18%) with histologic types other than invasive ductal carcinoma. All patients had been treated by breast-conserving surgery and radiotherapy, including supplemental radiation to the tumor bed. For 67 patients with predominantly lobular carcinomas, the actuarial overall 5-year survival was 100% and 77% for node-negative and node-positive patients, respectively. The actuarial probability of recurrence in the treated breast (13.5% at 5 years) appeared to be somewhat greater than that observed after treatment of invasive ductal cancers (8.8% at 5 years, P = 0.11). Of 12 mammary recurrences in patients with lobular carcinoma, four occurred at a considerable distance from the original primary and seven were multifocal, involving more than one quadrant in five patients. Of 47 patients with strictly in situ carcinomas, one patient whose axillary nodal status had not been determined subsequently developed distant metastases. Three additional patients developed mammary recurrence, two at the primary tumor site and one in another quadrant. The actuarial 5-year mammary recurrence and overall survival rates were 4% and 98%, respectively. For 27 patients with true medullary cancers, overall survival at 5 years was 90%. One localized mammary recurrence was observed at the site of the original primary. Actuarial mammary recurrence rate was 4% at 5 years. No relapse was observed in ten patients with colloid and one patient with adenoid cystic carcinoma. The authors conclude that, in addition to its well-established efficacy in the treatment of infiltrating ductal carcinomas, the combination of tumor excision and radiotherapy appears to provide adequate local control for other histologic types as well. However, patients with lobular cancer appear to be at somewhat greater risk of mammary failure, and recurrences in such patients tend to be multifocal and multicentric. PMID:2538219

  16. A Phase I Study of LJM716 in Squamous Cell Carcinoma of Head and Neck, or HER2+ Breast Cancer or Gastric Cancer

    ClinicalTrials.gov

    2014-04-21

    HER2 + Breast Cancer, HER2 + Gastric Cancer, Squamous Cell Carcinoma of Head and Neck, Esophageal Squamous Cell Carcinoma; HER2 + Breast Cancer; HER2 + Gastric Cancer; Squamous Cell Carcinoma of Head and Neck; Esophageal Squamous Cell Carcinoma

  17. Gynecomastia With Atypical Ductal Hyperplasia and Ductal Carcinoma In Situ Associated With Invasive Breast Carcinoma in a Male Patient on Antiretroviral Therapy: A Case Report.

    PubMed

    Coyne, John D

    2016-04-01

    Breast carcinoma in males is rare although a 4-fold increased incidence is reported in HIV-infected men. Herein we report a case of invasive breast carcinoma in a HIV-positive man on antiretroviral therapy. The carcinoma was associated with features of florid gynecomastia, atypical ductal hyperplasia, ductal carcinoma in situ, and columnar cell change. This combination of morphological changes has not previously been reported in the context of male breast carcinoma and their etiopathological associations are discussed. PMID:26612847

  18. Synchronous unilateral triple breast cancers composed of invasive ductal carcinoma, invasive lobular carcinoma, and Paget's disease.

    PubMed

    Onoe, Shunsuke; Tsuda, Hitoshi; Akashi-Tanaka, Sadako; Hasebe, Takahiro; Iwamoto, Eriko; Hojo, Takashi; Kinoshita, Takayuki

    2014-03-01

    We report a case of synchronous unilateral triple breast cancers comprising invasive ductal carcinoma (IDC), invasive lobular carcinoma (ILC), and Paget's disease. A 57-year-old woman with a left breast mass was referred to our hospital. Mammography revealed only an isodense area with foci of microcalcification in the lateral area of the left breast. Ultrasonography revealed 2 hypoechoic masses in the outer lower and inner upper areas, and these 2 lesions were diagnosed by core needle biopsy as ILC and IDC, respectively. Left total mastectomy with sentinel lymph node biopsies was performed. In addition to the ILC and IDC, histological examination also identified Paget's disease. Breast cancer often manifests as multiple unilateral lesions; however, it is sometimes difficult to determine whether these tumors have developed multicentrically or have multifocally invaded from an intraductal carcinoma. This case was clearly diagnosed to have occurred multicentrically because of the absence of continuity among the 3 tumors, the presence of a non-invasive component in all 3 tumors, and different histopathological findings. The synchronous unilateral development of ILCs is well known. Cases of synchronous unilateral triple or more breast cancers were reviewed, and their histopathological characteristics, including the incidence of Paget's disease, is discussed. PMID:21140247

  19. 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

  20. Heterogeneity of Bcl-2 expression in metastatic breast carcinoma.

    PubMed

    Subhawong, Andrea Proctor; Nassar, Hind; Halushka, Marc K; Illei, Peter B; Vang, Russell; Argani, Pedram

    2010-08-01

    Bcl-2 is an antiapoptotic protein that promotes cell survival, but also may block proliferation. In breast cancer, bcl-2 expression correlates with favorable prognosis and estrogen receptor (ER) positivity. However, experimental data have paradoxically suggested that bcl-2 promotes chemoresistance and metastasis. A direct and comprehensive comparison of bcl-2 expression between primary breast carcinomas and paired distant metastases has not been performed. We completed rapid autopsies on 17 patients with archived primary tumors and metastatic breast carcinoma, and created single-patient tissue microarrays containing each patient's primary tumor and matched metastases. Expression of bcl-2, ER, progesterone receptor, and HER-2 in primary tumors and matched metastases were compared by immunohistochemistry. All 11 ER-positive cases showed bcl-2 labeling in the primary tumor, whereas only 3 of 6 ER-negative cases did (P=0.029). In 10 cases, bcl-2 labeling in metastases was similar to that of the primary, although 3 cases showed significant variation among metastases. In six other cases, bcl-2 labeling was lost or significantly diminished in metastases. Five of the latter cases were Luminal A (ER-positive, HER-2-negative) primaries, three of which lost hormone receptors in metastases. Only 1 of 17 cases showed an increase in bcl-2 labeling in metastases compared with the paired primary tumor. In conclusion, bcl-2 is infrequently upregulated in metastatic breast carcinoma. Instead, downregulation of bcl-2 expression may occur in the setting of hormone therapy resistance. Our findings call into question the potential utility of anti-bcl-2 therapy in metastatic breast cancer. PMID:20495533

  1. Metaplastic carcinoma of the breast: an immunohistochemical study

    PubMed Central

    2014-01-01

    Background Metaplastic breast carcinoma is a rare entity of breast cancer expressing epithelial and/or mesenchymal tissue within the same tumor. The aim of this study is to evaluate the clinicopathological features of metaplastic breast carcinoma and to confirm the triple negative, basal-like and/or luminal phenotype of this type of tumor by using immunohistochemical staining. Methods Seven cases of MBC were evaluated for clinico-pathological features including follow up data. Cases were studied immunohistochemically by CK-Pan, Vimentin, ER, PR, HER2, basal markers (CK5/6, p63, EGFR, SMA and S-100), luminal cytokeratins (CK8, CK18 and CK19), markers for syncytial cells (β-HCG and PLAP), as well as prognostic markers (p53, ki-67 and calretinin). Results The mean age of the patients was 36 years. Three cases showed choriocarcinomatous features. All of our cases were negative for ER, PR and HER2. Six out of the 7 cases showed basal-like differentiation by demonstrating positivity with at least one of the basal/myoepithelial markers. Also 6 out of the 7 cases expressed luminal type cytokeratins (CK8, CK18 and/or CK19). P53 was positive in 3 cases, ki-67 was strongly expressed in only one case, while calretinin was expressed in 6 cases. Conclusion Metaplastic breast carcinoma presents in our population at a younger age group than other international studies. All cases are categorized immunohistochemically under the triple negative group of breast cancer and 86% of them exhibited basal-like and luminal phenotype. Majority of cases developed local recurrence and distant metastasis in a relatively short period of time. Virtual Slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1101289295115804 PMID:25030022

  2. Photodynamic therapy (PDT) for locally recurrent breast carcinoma

    NASA Astrophysics Data System (ADS)

    Gahlen, Johannes; Stern, Josef; Graschew, Georgi; Kaus, Michael R.; Herfarth, Christian

    1995-03-01

    Locally recurrent breast carcinoma and skin metastasisses on the chest wall can be difficult to treat. Conventional treatments like radiation-, chemo- and hormonal therapy have shown poor results in these patients. In comparison to this, PDT has some advantages and less side effects. We can observe a tumor accumulation of a systemic applied photosensitizer (PS). The PS can be stimulated by light of a wavelength of 630 nm and a phototoxic effect in the tumor occurs. We treated 7 patients with locally recurrent breast carcinoma 15 times with PDT. The intravenous application of the PS (Photofrin II, 1.5 mg/kg BW) was done 24 - 96 hours before local laser light radiation. The light source was an Ar-Dye laser with a wavelength of 630 nm. Due to a local tumor necrosis we observed a tumor reduction in each case. In 5 patients we saw a complete local remission with a good cosmetic result. Side effects were rare. All patients suffered from pain in the treated area. No major phototoxicity effects were seen. PDT can induce complete local tumor remissions in patients with cutaneous metastasisses after locally recurrent breast carcinoma. In absence of other metastasisses PDT is possibly a curative treatment. One of the major advantages of this treatment are the rare side effects, rare complications and the possible repetition of the PDT.

  3. Regulation of in situ to invasive breast carcinoma transition

    SciTech Connect

    Polyak, Kornelia; Hu, Min; Yao, Jun; Carroll, Danielle K.; Weremowicz, Stanislawa; Chen, Haiyan; Carrasco, Daniel; Richardson, Andrea; Violette, Shelia; Gelman, Rebecca S.; Bissell, Mina J.; Schnitt, Stuart; Polyak, Kornelia

    2008-05-07

    The transition of ductal carcinoma in situ (DCIS) to invasive carcinoma is a key event in breast tumor progression that is poorly understood. Comparative molecular analysis of tumor epithelial cells from in situ and invasive tumors has failed to identify consistent tumor stage-specific differences. However, the myoepithelial cell layer, present only in DCIS, is a key distinguishing and diagnostic feature. To determine the contribution of non-epithelial cells to tumor progression, we analyzed the role of myoepithelial cells and fibroblasts in the progression of in situ carcinomas using a xenograft model of human DCIS. Progression to invasion was promoted by fibroblasts, but inhibited by normal myoepithelial cells. The invasive tumor cells from these progressed lesions formed DCIS rather than invasive cancers when re-injected into naive mice. Molecular profiles of myoepithelial and epithelial cells isolated from primary normal and cancerous human breast tissue samples corroborated findings obtained in the xenograft model. These results provide the proof of principle that breast tumor progression could occur in the absence of additional genetic alterations and that tumor growth and progression could be controlled by replacement of normal myoepithelial inhibitory signals.

  4. Regulation of In Situ to Invasive Breast CarcinomaTransition

    SciTech Connect

    Hu, Min; Carroll, Danielle K.; Weremowicz, Stanislawa; Chen,Haiyan; Carrasco, Daniel; Richardson, Andrea; Bissell, Mina; Violette,Shelia; Gelman, Rebecca S.; Schnitt, Stuart; Polyak, Kornelia

    2007-03-13

    The transition of ductal carcinoma in situ (DCIS) to invasive carcinoma is a key event in breast tumor progression that is poorly understood. Comparative molecular analysis of tumor epithelial cells from in situ and invasive tumors has failed to identify consistent tumor stage-specific differences. However, the myoepithelial cell layer, present only in DCIS, is a key distinguishing and diagnostic feature. To determine the contribution of non-epithelial cells to tumor progression, we analyzed the role of myoepithelial cells and fibroblasts in the progression of in situ carcinomas using a xenograft model of human DCIS. Progression to invasion was promoted by fibroblasts, but inhibited by normal myoepithelial cells. The invasive tumor cells from these progressed lesions formed DCIS rather than invasive cancers when re-injected into naive mice. Molecular profiles of myoepithelial and epithelial cells isolated from primary normal and cancerous human breast tissue samples corroborated findings obtained in the xenograft model. These results provide the proof of principle that breast tumor progression could occur in the absence of additional genetic alterations and that tumor growth and progression could be controlled by replacement of normal myoepithelial inhibitory signals.

  5. Concomitant Small Cell Neuroendocrine Carcinoma of Gallbladder and Breast Cancer

    PubMed Central

    Aiello, Paolo; Aragona, Francesco; Territo, Valentina; Caruso, Anna Maria; Patti, Rosalia; Buscemi, Salvatore; Di Vita, Gaetano

    2014-01-01

    The neuroendocrine carcinoma is defined as a high-grade malignant neuroendocrine neoplasm arising from enterochromaffin cells, usually disposed in the mucosa of gastric and respiratory tracts. The localization in the gallbladder is rare. Knowledge of these gallbladder tumors is limited and based on isolated case reports. We describe a case of an incidental finding of small cell neuroendocrine carcinoma of the gallbladder, observed after cholecystectomy for cholelithiasis, in a 55-year-old female, who already underwent quadrantectomy and sentinel lymph-node biopsy for breast cancer. The patient underwent radiotherapy for breast cancer and six cycles of chemotherapy with cisplatin and etoposide. Eighteen months after surgery, the patient was free from disease. Small cell neuroendocrine carcinoma of the gallbladder has poor prognosis. Because of the rarity of the reported cases, specific prognostic factors have not been identified. The coexistence of small cell neuroendocrine carcinoma of the gallbladder with another malignancy has been reported only once. The contemporary presence of the two neoplasms could reflect that bioactive agents secreted by carcinoid can promote phenotypic changes in susceptible cells and induce neoplastic transformation. PMID:25328753

  6. Comparative proteomic analysis of ductal and lobular invasive breast carcinoma.

    PubMed

    Oliveira, N C S; Gomig, T H B; Milioli, H H; Cordeiro, F; Costa, G G; Urban, C A; Lima, R S; Cavalli, I J; Ribeiro, E M S F

    2016-01-01

    Breast cancer is the second most common cancer worldwide and the first among women. Invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) are the two major histological subtypes, and the clinical and molecular differences between them justify the search for new markers to distinguish them. As proteomic analysis allows for a powerful and analytical approach to identify potential biomarkers, we performed a comparative analysis of IDC and ILC samples by using two-dimensional electrophoresis and mass spectrometry. Twenty-three spots were identified corresponding to 10 proteins differentially expressed between the two subtypes. ACTB, ACTG, TPM3, TBA1A, TBA1B, VIME, TPIS, PDIA3, PDIA6, and VTDB were upregulated in ductal carcinoma compared to in lobular carcinoma samples. Overall, these 10 proteins have a key role in oncogenesis. Their specific functions and relevance in cancer initiation and progression are further discussed in this study. The identified peptides represent promising biomarkers for the differentiation of ductal and lobular breast cancer subtypes, and for future interventions based on tailored therapy. PMID:27173185

  7. EVOLUTION OF SYNCHRONOUS BILATERAL BREAST CARCINOMA IN A YOUNG PATIENT.

    PubMed

    Manea, Elena; Munteanu, Anca

    2016-01-01

    Bilateral breast cancer incidence is appreciated to be between 0.3 to 12% and is determined either by a hereditary load associated with chromosomal instability under the effect of environmental factors, or by the evolution in a particular hormonal context which gives biological aggressiveness. We present the case of a patient, aged 38 years, clinically, imagistic and bioptic diagnosed with left axillary lymph node metastases of breast carcinoma NST invasive G3, IHC-RE = 60%, RP = 30%, HER2neu = 2 +, Ki67 = 20%, in August 2013. Patient followed neoadjuvant chemotherapy treatment during September-October 2013. In December 2013 she was clinically and imaging diagnosed with bilateral breast cancer, for which surgical intervention was done which consisted of bilateral radical Madden mastectomy with bilateral axillary lymphadenectomy. BAP-invasive carcinoma NST: left breast-pT2mN3a G2, right breast--pT3mN3a G2, IHC-RE = 90%, RP =70% HER2neu = 2 +, Ki67 = 50%. During the period of January-March 2014, the patient followed adjuvant chemotherapy and Herceptin. Bilateral breast ultrasound assessment in April 2014 revealed: left axilla--liquid blade 29 / 6mm; right axilla--oval ganglion 9/5 mm. Abdominal and pelvic ultrasound: empty uterine cavity, bosselated contour; at left ovary level multiple cystic formations. During the period of May-June 2014, adjuvant radiation therapy and ovarian irradiationwas administered to the patient. Subsequently hormone therapy was initiated. Following CHT / ovarian irradiation patient continues to experience intermittent uterine bleeding, which is why a total hysterectomy with bilateral ovariectomy was done, and BAP: cervical, endometrialand left ovary with tumor multifocal infiltration with histopathological aspect of invasive breast carcinoma NST. Periodic imaging evaluations do not reveal local or distant recurrence. The particularity of this case is synchronous bilateral breast cancer diagnosis in a young patient complicated in its

  8. Management of ductal carcinoma in situ of the breast.

    PubMed Central

    Carty, N. J.; Carter, C.; Royle, G. T.; Johnson, C. D.

    1995-01-01

    The advent of mammographic breast screening has increased the detection of ductal carcinoma in situ (DCIS), which now accounts for 15-20% of all breast cancer. While symptomatic DCIS has been treated satisfactorily by mastectomy, this may be an overtreatment of smaller screen-detected lesions. Although local excision, with or without radiotherapy, is associated with a significant risk of local recurrence of DCIS or invasive cancer, salvage surgery is usually successful. The long-term breast-specific mortality rate of treatment by mastectomy and local excision are similar. Whereas mastectomy is still appropriate for women with lesions > 30 mm in diameter or centrally placed and for those women who demand the best possible disease-free survival, local surgery should otherwise be considered. PMID:7598411

  9. Breast Carcinoma With Unrecognized Neuroendocrine Differentiation Metastasizing to the Pancreas: A Potential Diagnostic Pitfall.

    PubMed

    Christensen, Lene; Mortensen, Michael Bau; Detlefsen, Sönke

    2016-08-01

    The current World Health Organization classification recognizes 3 subtypes of breast carcinomas with neuroendocrine features. Their reported prevalence is highly variable, ranging from <1% to up to 20% of all breast carcinomas. We report the case of a 73-year-old woman who underwent lumpectomy with a postoperative diagnosis of invasive ductal breast carcinoma. Six weeks after lumpectomy, pancreatic biopsies showed tumor cells with neuroendocrine features. The first immunohistochemical panel showed positivity for synaptophysin and cytokeratins, raising suspicion of a pancreatic neuroendocrine tumor. However, a second panel revealed positivity for estrogen receptors and GATA3. On review of the lumpectomy specimen, a significant neuroendocrine component was found, leading to the final diagnosis of breast carcinoma with neuroendocrine features metastasizing to the pancreas. Neuroendocrine markers are not routinely analyzed in breast tumors. Hence, metastases from breast carcinomas with unrecognized neuroendocrine features may lead to false diagnoses of primary neuroendocrine tumors at different metastatic sites, such as the pancreas. PMID:26912472

  10. "Secretory" Carcinoma of the Skin Mimicking Secretory Carcinoma of the Breast: Case Report and Literature Review.

    PubMed

    Huang, Sixia; Liu, Yan; Su, Jing; Liu, Jianying; Guo, Xiaoning; Mei, Fang; Zheng, Jie; Liao, Songlin

    2016-09-01

    Secretory carcinoma is a unique kind of adenocarcinoma. It has distinct histological features and a special genetic change, that is, t (12; 15) (p13; q25) translocation which leads to the expression of the ETV6-NTRK3 fusion gene. Secretory carcinoma has been found to occur both in the breast and salivary gland. Here the authors present a case of 22-year-old woman with a unique cutaneous neoplasm located at the axilla. The tumor was characterized histologically with the formation of round to ovoid microcysts and papillary structure, which was similar to the secretory carcinoma of the breast and salivary gland. Furthermore, the gene sequence analysis of reverse-transcription polymerase chain reaction products demonstrated the expression of the ETV6-NTRK3 fusion gene. To the authors' knowledge, this is the first case of secretory carcinoma from the skin which has the same genetic change as those from the breast and salivary gland. Local excision was performed on this patient. She had been followed up for nearly 1 year. No recurrence or metastasis was found yet. PMID:26981741

  11. Metastatic prostatic adenocarcinoma mimicking inflammatory breast carcinoma: a case report.

    PubMed

    Njiaju, Uchenna O; Truica, Cristina I

    2010-02-01

    Prostate adenocarcinoma can manifest as a fairly indolent tumor or as a very aggressive cancer with significant invasive and metastatic potential. Common metastatic sites include bone, liver, lymph nodes, and adrenal glands. Dermatologic manifestations are rare. We present a case of a man who presented with breast skin changes that mimicked inflammatory breast carcinoma with specialized testing ultimately giving a diagnosis of metastatic prostatic adenocarcinoma. A 78-year-old man presented with left breast redness and swelling. Examination revealed an erythematous rash with subcutaneous edema over the left hemithoracic area. A breast ultrasound showed no focal mass, and a breast core biopsy had no evidence of tumor. A skin biopsy showed metastatic carcinoma in dermal lymphatics, and the tumor was found to have no estrogen or progesterone receptors or HER2 expression. Computed tomography scans, positron emission tomography, and a nuclear bone scan revealed widespread skeletal metastases. The patient received a 3-month course of capecitabine and cyclophosphamide with no improvement in his skin lesions. Subsequent immunohistochemical staining on the tumor specimen was positive for prostate-specific antigen (PSA) and alpha-methyl-CoA-racemase, confirming a diagnosis of metastatic prostatic adenocarcinoma. He received leuprolide and bicalutamide and demonstrated significant improvement with near-complete resolution of his skin lesions and a decrease in his PSA level. Prostatic adenocarcinoma presenting initially as a breast malignancy is a rarely recognizable clinical event. Undoubtedly, increased awareness and recognition of the rare entity described herein will allow for the prompt initiation of specific therapies, which might be of benefit to many patients. PMID:20133250

  12. Lupus mastitis: a mimicker of breast carcinoma

    PubMed Central

    Warne, Richard Roger; Taylor, Donna; Segal, Amanda; Irish, Ashley

    2011-01-01

    The authors present a case of lupus mastitis which was initially diagnosed following an incisional biopsy of a breast lump, with similar pathology found 2 years later after an ultrasound guided biopsy of the same lump. The woman had been diagnosed 7 years before with systemic lupus erythematosus. The radiological and pathological features are presented in this report with discussion of similar cases in the literature. PMID:22669997

  13. Carcinoma originating from aberrant breast tissue of the right upper anterior chest wall : a case report.

    PubMed Central

    Rho, J. Y.; Juhng, S. K.; Yoon, K. J.

    2001-01-01

    Aberrant breast tissue is usually found in proximity to the normal breast, that is, in the axillary, sternal or clavicular regions. Carcinoma occurs more frequently in the aberrant tissue of the axilla than the extra-axillary site though the overall incidence of tumors of aberrant breast tissue is low. To our knowledge, studies regarding the carcinoma of aberrant breast tissue of the extra-axillary site have been reported rarely. Here we report a recent case of carcinoma originating from the extra-axillary aberrant breast tissue, presenting as a subcutaneous nodule on the right upper anterior chest wall. It is suggested that subcutaneous nodules of uncertain origin around the periphery of the breast should be suspected for breast carcinoma as a differential diagnosis and treated properly. PMID:11511802

  14. Locoregional Treatment for Breast Carcinoma After Hodgkin's Lymphoma: The Breast Conservation Option

    SciTech Connect

    Haberer, Sophie; Belin, Lisa; Le Scodan, Romuald; Kirova, Youlia M.; Savignoni, Alexia; Stevens, Denise; Moisson, Patricia; Decaudin, Didier; Pierga, Jean-Yves; Reyal, Fabien; Campana, Francois; Fourquet, Alain; Bollet, Marc A.

    2012-02-01

    Purpose: To report clinical and pathologic characteristics and outcome of breast cancer (BC) after irradiation for Hodgkin's lymphoma (HL) in women treated at the Institut Curie, with a special focus on the breast-conserving option. Methods and Materials: Medical records of 72 women who developed either ductal carcinoma in situ or Stage I-III invasive carcinoma of the breast after HL between 1978 and 2009 were retrospectively reviewed. Results: Median age at HL diagnosis was 23 years (range, 14-53 years). Median total dose received by the mediastinum was 40 Gy, mostly by a mantle-field technique. Breast cancers occurred after a median interval of 21 years (range, 5-40 years). Ductal invasive carcinoma and ductal carcinoma in situ represented, respectively, 51 cases (71%) and 14 cases (19%). Invasive BCs consisted of 47 cT0-2 tumors (82%), 5 cN1-3 tumors (9%), and 20 Grade 3 tumors (35%). Locoregional treatment for BCs consisted of mastectomy with (3) or without (36) radiotherapy in 39 patients and lumpectomy with (30) or without (2) adjuvant radiotherapy in 32 patients. The isocentric lateral decubitus radiation technique was used in 17 patients after breast-conserving surgery (57%). With a median follow-up of 7 years, 5-year overall survival rate and locoregional control rate were, respectively, 74.5% (95% confidence interval [CI], 64-88%) and 82% (95% CI, 72-93%) for invasive carcinoma and 100% (95% CI, 100 -100%) and 92% (95% CI, 79-100%) for in situ carcinoma. In patients with invasive tumors, the 5-year distant disease-free survival rate was 79% (95% CI, 69-91%), and 13 patients died of progressive BC. Contralateral BC was diagnosed in 10 patients (14%). Conclusions: Breast-conserving treatment can be an option for BCs that occur after HL, despite prior thoracic irradiation. It should consist of lumpectomy and adjuvant breast radiotherapy with use of adequate techniques, such as the lateral decubitus isocentric position, to protect the underlying heart and

  15. The immune microenvironment of breast ductal carcinoma in situ.

    PubMed

    Thompson, Elizabeth; Taube, Janis M; Elwood, Hillary; Sharma, Rajni; Meeker, Alan; Warzecha, Hind Nassar; Argani, Pedram; Cimino-Mathews, Ashley; Emens, Leisha A

    2016-03-01

    The host immune response has a key role in breast cancer progression and response to therapy. However, relative to primary invasive breast cancers, the immune milieu of breast ductal carcinoma in situ (DCIS) is less understood. Here, we profile tumor infiltrating lymphocytes and expression of the immune checkpoint ligand programmed death ligand 1 (PD-L1) in 27 cases of DCIS with known estrogen receptor (ER), progesterone receptor, and human epidermal growth factor 2 (HER-2) expression using tissue microarrays. Twenty-four cases were pure DCIS and three had associated invasive ductal carcinoma. Tumors were stained by immunohistochemistry for PD-L1, as well as the lymphocyte markers CD3, CD4, CD8, FoxP3, and CD20. The expression of PD-L1 by DCIS carcinoma cells and tumor infiltrating lymphocytes was determined, and the average tumor infiltrating lymphocytes per high power field were manually scored. None of the DCIS cells expressed PD-L1, but 81% of DCIS lesions contained PD-L1+ tumor infiltrating lymphocytes. DCIS with moderate-diffuse tumor infiltrating lymphocytes was more likely to have PD-L1+ tumor infiltrating lymphocytes (P=0.004). Tumor infiltrating lymphocytes with high levels of PD-L1 expression (>50% cells) were seen only in triple-negative DCIS (P=0.0008), and PD-L1-tumor infiltrating lymphocytes were seen only in ER+/HER-2-DCIS (P=0.12). The presence of PD-L1+ tumor infiltrating lymphocytes was associated with a younger mean patient age (P=0.01). Further characterization of the DCIS immune microenvironment may identify useful targets for immune-based therapy and breast cancer prevention. PMID:26769139

  16. A case of Meigs syndrome mimicking metastatic breast carcinoma

    PubMed Central

    Lanitis, Sophocles; Sivakumar, Sivahamy; Behranwala, Kasim; Zacharakis, Emmanouil; Al Mufti, Ragheed; Hadjiminas, Dimitri J

    2009-01-01

    Background Adnexal masses are not uncommon in patients with breast cancer. Breast cancer and ovarian malignancies are known to be associated. In patients with breast cancer and co-existing pleural effusions, ascites and adnexal masses, the probability of disseminated disease is high. Nevertheless, benign ovarian masses can mimic this clinical picture when they are associated with Meigs' syndrome making the work-up and management of these patients challenging. To our knowledge, there are no similar reports in the literature and therefore we present this case to highlight this entity. Case presentation A 56-year old woman presented with a 4 cm, grade 2, invasive ductal carcinoma of her left breast. Pre-treatment staging investigations showed a 13.5 cm mass in her left ovary, a small amount of ascites and a large right pleural effusion. Serum tumour markers showed a raised CA125 supporting the malignant nature of the ovarian mass. The cytology from the pleural effusion was indeterminate but thoracoscopic biopsy failed to show malignancy. The patient was strongly against mastectomy and she was commenced on neo-adjuvant Letrozole 2.5 mg daily with a view to perform breast conserving surgery. After a good response to the hormone manipulation, the patient had breast conserving surgery, axillary sampling and laparoscopic excision of the ovarian mass which was eventually found to be a benign ovarian fibroma. Conclusion Despite the high probability of disseminated malignancy when an ovarian mass associated with ascites if found in a patient with a breast cancer and pleural effusion, clinicians should be aware about rare benign syndromes, like Meigs', which may mimic a similar picture and mislead the diagnosis and management plan. PMID:19161612

  17. A case of renal cell carcinoma metastasizing to invasive ductal breast carcinoma.

    PubMed

    Chen, Tai-Di; Lee, Li-Yu

    2014-02-01

    Tumor-to-tumor metastasis is an uncommon but well-documented phenomenon. We present a case of a clear cell renal cell carcinoma (RCC) metastasizing to an invasive ductal carcinoma (IDC) of the breast. A 74-year-old woman with a past history of clear cell RCC status after radical nephrectomy underwent right modified radical mastectomy for an enlarging breast mass 3 years after nephrectomy. Histological examination revealed a small focus with distinct morphological features similar to clear cell RCC encased in the otherwise typical IDC. Immunohistochemical studies showed that this focus was positive for CD10 and vimentin, in contrast to the surrounding IDC, which was negative for both markers and positive for Her2/neu. Based on the histological and immunohistochemical features, the patient was diagnosed with metastasis of clear cell RCC to the breast IDC. To the best of our knowledge, this is the first reported case of a breast neoplasm as the recipient tumor in tumor-to-tumor metastasis. PMID:24530247

  18. Comparative evaluation of six cytological grading systems in breast carcinoma

    PubMed Central

    Saha, Kaushik; Raychaudhuri, Gargi; Chattopadhyay, Bitan Kuamr; Das, Indranil

    2013-01-01

    Background: Cytological grading is a useful tool for selection of therapy and prognosis in breast carcinoma. Despite having many cytological grading systems, there is still no agreement among pathologists to accept one of them as a gold standard. Aim: This study was undertaken to evaluate six such three-tier cytological grading systems to determine which system corresponds best to histological grading done by Nottingham modification of Scarff Bloom Richardson (SBR)'s method. Materials and Methods: In a double-blind study, preoperative cytological grades obtained by six systems on fine-needle aspiration cytology (FNAC) smears were compared by testing concordance, association and correlation with histological grade derived postoperatively by the SBR's method in 57 patients of breast carcinoma. Bivariate correlation studies and multiple linear regressions were done to assess the significance of the different cytological parameters to predict final cytological grades. Results: Robinson's system demonstrated the best correlation (ρ = 0.799; P = 0.000 and τ = 0.765; P = 0.000), maximum percent agreement (77.19%) and a substantial kappa value of agreement (κ = 0.62) with the SBR's grading system. All the six cytological grading systems correlated with histological grading strongly and positively. In multiple regression analysis, all of the cytological parameters of Robinson's system except cell size and nucleoli had significance in predicting the final cytological grade. Conclusions: Robinson's grading system is simple, more objective and reproducible, and demonstrated the best concordance with histological grading. So, Robinson's system should be used routinely for breast carcinoma aspirates. PMID:23833396

  19. Liver metastases of breast carcinoma detected on /sup 99m/Tc-methylene diphosphonate bone scan

    SciTech Connect

    Baumert, J.E.; Lantieri, R.L.; Horning, S.; McDougall, I.R.

    1980-02-01

    The accumulation of bone-seeking radiopharmaceuticals has been reported in liver metastases from colon carcinoma and oat cell carcinoma of the lung. Two patients with breast carcinoma in whom hepatic metastases were visualized on /sup 99m/Tc-methylene diphosphonate bone images are described. This has not been previously reported.

  20. Accessory breast cancer occurring concurrently with bilateral primary invasive breast carcinomas: a report of two cases and literature review.

    PubMed

    Hao, Jin-Yan; Yang, Cui-Cui; Liu, Fang-Fang; Yang, Yi-Ling; Li, Shuai; Li, Wei-Dong; Li, Ya-Qing; Lang, Rong-Gang; Fan, Yu; Paulos, Estifanos; Zhang, Xin-Min; Fu, Li

    2012-09-01

    The development of accessory breast tissue, which is found anywhere along the milk line, is attributed to the failure of milk line remnants to regress during embryogenesis. Primary tumors may arise from any ectopic breast tissue. Accessory breast cancer occurring concurrently with primary invasive breast cancer is extremely rare. Two such cases were reported in this article. One was a 43-year-old Chinese female who exhibited bilateral breast cancer (invasive ductal carcinoma, not otherwise specified, IDC-NOS) and an accessory breast carcinoma (IDC-NOS) incidentally identified in her left axilla. The ectopic breast tissue in her right axilla presented with adenosis. The patient was surgically treated, followed by postoperative docetaxel epirubicin (TE) chemotherapy. The second case was a 53-year-old Chinese female with bilateral breast cancer (apocrine carcinoma) accompanied by an accessory breast carcinoma (IDC-NOS) in her right axilla that was also incidentally identified. The patient was surgically treated after three doses of cyclophosphamide epirubicin docetaxel (CET) neoadjuvant chemotherapy, followed by adjuvant chemotherapy of the same regimen. PMID:23691479

  1. Desmoid tumor occurring after reconstruction mammaplasty for breast carcinoma.

    PubMed

    Dale, P S; Wardlaw, J C; Wootton, D G; Resnick, J I; Giuliano, A E

    1995-11-01

    We present a case of desmoid tumor associated with prior alloplastic breast reconstruction. Wide local excision that includes chest wall resection, if necessary, is the primary treatment of choice. Patients with extensive nonresectable or recurrent disease may benefit from radiation therapy. Systemic therapy is a possibility in certain cases, but its toxicity generally precludes its use with this nonmetastatic tumor. Although this is the fourth reported case of desmoid tumor arising after implantation of a silicone prosthesis, we cannot claim a causal relationship. Careful follow-up consisting of yearly physical and mammagraphic examinations may facilitate early diagnosis and treatment of locally aggressive desmoid tumors but is not warranted, except in the context of routine screening for breast carcinoma. PMID:8579271

  2. p53 alteration in morphologically normal/benign breast tissue in patients with triple-negative high-grade breast carcinomas: breast p53 signature?

    PubMed

    Wang, Xi; Stolla, Moritz; Ring, Brian Z; Yang, Qi; Laughlin, Todd S; Rothberg, Paul G; Skinner, Kristin; Hicks, David G

    2016-09-01

    p53 alterations have been identified in approximately 23% of breast carcinomas, particularly in hormone receptor-negative high-grade carcinomas. It is considered to be an early event in breast carcinogenesis. Nevertheless, the putative precursor lesion of high-grade breast carcinoma remains elusive. Breast excision specimens from 93 triple-negative high-grade invasive ductal carcinomas, 48 estrogen receptor (ER)-positive/progesterone receptor-positive/Her2-negative non-high-grade invasive ductal carcinomas, and 50 mammoplasty breasts were selected. At least 2 tissue blocks with tumor and adjacent benign tissue were sectioned and subjected to immunohistochemistry staining for p53. TP53 gene sequencing was performed on select tumors. Further immunohistochemistry staining for ER and Ki-67 was performed on consecutive sections of tissue with p53-positive normal/benign cells. Of the 93 high-grade carcinomas, 51 (55%) were positive for p53 alteration, whereas only 3 (6.25%) of the 48 non-high-grade carcinomas were p53 altered. Focal p53 positivity in adjacent normal/benign breast tissue was identified in 19 cases, and 18 of them also had p53 alteration in their carcinomas. Only 1 case had focal p53 staining in normal/benign tissue, but the tumor was negative for p53 alteration. No p53 staining positivity was identified in the mammoplasty specimens. The p53-stained normal/benign cells were ER negative and did not show an increase in the Ki-67 labeling index. These findings indicate that the p53 staining positivity in normal/benign breast tissue is not a random event. It could be considered as the "p53 signature" in breast and serve as an indicator for future potential risk of p53-positive high-grade breast carcinoma. PMID:27246177

  3. Accelerated Partial Breast Irradiation for Pure Ductal Carcinoma in Situ

    SciTech Connect

    Park, Sean S.; Grills, Inga Siiner; Chen, Peter Y.; Kestin, Larry L.; Ghilezan, Michel I.; Wallace, Michelle; Martinez, Alvaro M.; Vicini, Frank A.

    2011-10-01

    Purpose: To report outcomes for ductal carcinoma in situ (DCIS) treated with breast-conserving therapy using accelerated partial breast irradiation (APBI). Methods and Materials: From March 2001 to February 2009, 53 patients with Stage 0 breast cancer were treated with breast conserving surgery and adjuvant APBI. Median age was 62 years. All patients underwent excision with margins negative by {>=}1 mm before adjuvant radiotherapy (RT). A total of 39 MammoSite brachytherapy (MS) patients and 14 three-dimensional conformal external beam RT (3DCRT) patients were treated to the lumpectomy bed alone with 34 Gy and 38.5 Gy, respectively. Of the DCIS cases, 94% were mammographically detected. All patients with calcifications had either specimen radiography or postsurgical mammography confirmation of clearance. Median tumor size was 6 mm, and median margin distance was 5 mm. There were no statistically significant differences according to APBI method for race/ethnicity, tumor detection method, tumor grade, estrogen receptor (ER) status, or use of tamoxifen (p = NS). Recurrence and survival were calculated using the Kaplan-Meier method. Cosmesis was scored by the Harvard criteria. Results: With a median follow-up of 3.6 years (range, 0.4-6.3 years), the overall and cause-specific survival rates were 98% and 100%, respectively. Three-year actuarial ipsilateral breast tumor recurrence was 2%. One failure was observed at the resection bed 11 months post-RT. No other elsewhere breast failures, regional recurrences, or distant metastases were noted. Cosmesis was excellent or good in 92.4% of cases, with no statistically significant differences according to the APBI method (92.3% with MammoSite and 92.8% with 3DCRT; p = 0.649). Conclusions: APBI as part of breast-conserving therapy for pure DCIS was associated with excellent local control and survival rates, with the vast majority of patients having good to excellent cosmesis. This finding supports the recent analysis by the

  4. Unusual case of calciphylaxis associated with metastatic breast carcinoma.

    PubMed

    Bosler, David S; Amin, Mitual B; Gulli, Farris; Malhotra, Rajwant K

    2007-08-01

    Calciphylaxis is a relatively rare disorder associated with calcification of small- and medium-sized blood vessels, progressive ischemic skin necrosis, and ulcerations. It is usually seen in patients with end-stage renal disease with secondary hyperparathyroidism and is occasionally seen in primary hyperparathyroidism, hypercalcemia of malignancy, and end-stage liver disease. We report an unusual case of calciphylaxis seen in association with metastatic breast carcinoma in the absence of end-stage renal or parathyroid disease. A 73-year-old woman presented with painful leg ulcers. Serum calcium levels and parathormone levels were within normal limits. Skin biopsies from the ulcers revealed small- to medium-sized subcutaneous arteries with calcification of the media. Some of the arteries were narrowed by fibrointimal hyperplasia and fibrin thrombi. Calcification of the subcutaneous fat, fat necrosis, and suppuration were also seen. Calciphylaxis associated with metastatic osteolytic breast carcinoma is rare. Although end stage renal disease with secondary hyperparathyroidism is the most common cause of calciphylaxis, this case demonstrates that less common conditions with normal serum calcium and parathormone levels may also cause it. PMID:17667177

  5. Female breast carcinomas: nuclear and cytoplasmic proteins versus steroid receptors.

    PubMed

    Bryś, M; Romanowicz-Makowska, H; Nawrocka, A; Krajewska, W M

    2000-01-01

    Nuclear and cytoplasmic proteins of human female breast cancer were analysed by one-dimensional sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE). Oestrogen receptor and progesterone receptor expression was determined by semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) method. The electropherograms were developed by silver nitrate staining and quantitative analysis was carried out by video densitometer using the software Gel-Pro Analyzer. Nuclear and cytoplasmic proteins of breast carcinomas and normal tissue differed both qualitatively and quantitatively. Nuclear polypeptides of 108, 53 and 48 kD as well as the 36 kD cytoplasmic polypeptide were specific for tumour samples, while the 51 kD nuclear polypeptide was detected only in normal tissue. Quantitative differences in band density were noted in the 32 kD nuclear polypeptide. This polypeptide was expressed in greatest concentration in infiltrating ductal carcinomas which also indicated the greatest oestrogen receptor gene expression. This relationship appeared to be statistically significant (p < 0.005). No correlations were evident between the 32 kD protein expression and the progesterone receptor gene expression in any of the tissue types examined, nor between the 32 kD protein and the patient's age or tumour grade. PMID:10756981

  6. Management of neuroendocrine carcinomas of the breast: A rare entity

    PubMed Central

    Yildirim, Yesim; Elagoz, Sahende; Koyuncu, Ayhan; Aydin, Cengiz; Karadayi, Kursat

    2011-01-01

    Neuroendocrine (NE) carcinoma of the breast is extremely rare and constitutes less than 0.1% of all breast tumors. Only a few studies are currently available in the literature and a standard approach to treating this tumor has yet to be established. The aim of this study was to apply pathological treatment modalities in clinical practice and to select the most appropriate treatment accordingly. Six female patients were diagnosed with primary NE carcinoma of the breast. The patients underwent modified radical mastectomy with axillary dissection. Pathological specimens were stained with hematoxylin and eosin and an immunohistochemical panel of antibodies [neuron-specific enolase (NSE), chromogranin, synoptophysin, estrogen and progesterone receptor, c-erbB2 and Ki-67]. The results showed that tumor size ranged from 2 to 4.5 cm in diameter. Lymph node metastasis was detected in 4 (67%) patients. Estrogen and progesterone receptor expression was found in 5 (83%) patients. None of the patients expressed c-erbB2. Chromogranin was found to be positive in 5 (83%) patients. Synoptophysin expression was detected in 5 (83%) patients. NSE was stained in 4 (67%) patients. An intraductal component was found in 5 (83%) patients. Lymphovascular invasion was found in 5 (83%) patients. Adjuvant chemotherapy was administered to patients with a Ki-67 index of ≥10%. Radiotherapy was administered to 4 (67%) patients, and 4 (67%) patients received hormonal therapy. The mean follow-up time was 31.1 months (range 12-52). All 6 patients survived, although following chemotherapy and tamoxifen, the disease progressed in 1 patient who received second-line hormonal therapy. In conclusion, NE carcinoma of the breast is a distinct entity. Management of this rare tumor may include surgery and radiotherapy depending on the size of the tumor and lymph node status. However, the exact role of chemotherapy and hormonal therapy has yet to be established. Adjuvant chemotherapy is recommended for

  7. Molecular subtypes of breast carcinoma in Saudi Arabia

    PubMed Central

    Alnegheimish, Norah A.; Alshatwi, Razan A.; Alhefdhi, Reem M.; Arafah, Maha M.; AlRikabi, Ammar C.; Husain, Sufia

    2016-01-01

    Objectives: To determine the distribution of various molecular subtypes of breast cancer in Saudi Arabia and to assess the association between these subtypes and age at diagnosis, tumor size, histopathological type, grade, presence of carcinoma in-situ, and lymph node status. Methods: This observational retrospective study, between January 2010 and December 2014, was conducted at King Khalid University Hospital, Riyadh, Saudi Arabia. We classified 359 breast cancers into 4 molecular subtypes, using immunohistochemistry: luminal A (estrogen receptor [ER], or progesterone receptor [PR] positive and human epidermal growth factor receptor 2 [HER2] negative), luminal B (ER and/or PR positive and HER2 positive), HER2-positive (ER and PR negative and HER2 positive), and triple negative (ER, PR, and HER2 negative). We evaluated the relationship between these subtypes and clinicopathological features using Chi square test. Results: The most prevalent subtype was luminal A (58.5%), followed in descending order of frequency by triple negative (14.8%), luminal B (14.5%), and HER2-positive (12.3%). The average age at diagnosis was 49.8 years, and average tumor size at diagnosis was 3.19 cm. Conclusion: Luminal A tumor was the most common molecular subtype and HER2-positive was the least common. Most lobular carcinomas were luminal A tumors. Human epidermal growth factor receptor 2-positive and triple negative tumors had a higher histologic grade and a larger tumor size at diagnosis, and they were more common in women under 50 years. Carcinoma-in-situ was least common in triple negative tumors. We found no association between lymph node status and molecular subtypes. PMID:27146612

  8. A reappraisal of oophorectomy in carcinoma of the breast.

    PubMed

    Veronesi, U; Cascinelli, N; Greco, M; Di Fronzo, G; Oriana, R; Merson, M; Galluzzo, D; Bufalino, R; Belli, F; Sacchini, V

    1987-01-01

    Bilateral oophorectomy was used to treat 601 patients with disseminated breast carcinoma from 1974-1984. The total response rate was 31.2%. Complete regression occurred in 10.5% of patients and partial regression occurred in 20.8%, whereas 28.3% of patients showed no change and the disease progressed in 36.9% of patients. The patients who had a total regression had good survival rates (60.8% at 5 years and 47.3% at 7 years). No significant differences were found in the various age groups or with different types of dissemination. Patients with syncronous primary carcinoma and distant metastases had a high rate of regression as did patients with slow-growing carcinomas that metastasized many years after primary treatment. Estrogen receptor (ER) rates were good indicators of response only when determined on metastatic tissue at the time of oophorectomy. The value of ER determined on the primary tumor was of limited predictivity of response. A total of 220 patients received chemotherapy before oophorectomy. In this group the response rate was 22.3%, lower than that observed in patients who did not receive chemotherapy (36.6%). No important differences in total response rates were found among patients with amenorrhea and without amenorrhea although total regressions were more frequent in the latter patients than in the former patients. PMID:3800458

  9. Optimal management of ductal carcinoma in situ of the breast.

    PubMed

    Sakorafas, George H; Farley, David R

    2003-12-01

    Ductal carcinoma in situ (DCIS) represents a breast lesion that is diagnosed with increasing frequency, mainly due to the wide use of screening mammography. Today, DCIS comprises 15-25% of all breast cancers detected at population screening programs. Consequently, the concepts of properly managing such patients assume a greater importance in everyday practice. Mammographically detected microcalcifications are the most common presentation of DCIS. Despite recent technological advances (including Stereotactic-guided directional vacuum-assisted biopsy), mammographically guided wire biopsy remains the "gold-standard" for obtaining a histological diagnosis in patients with non-palpable, mammographically detected DCIS. Management options include mastectomy, local excision combined with radiation therapy, and local excision alone. Given that DCIS is a heterogeneous group of lesions rather than a single entity, and because patients have a wide variety of personal needs that must be addressed during treatment selection, it is obvious that no single approach will be appropriate for all forms of DCIS or for all patients. Careful patient selection is of key importance in order to achieve the best results in the management of the individual patient with DCIS. Axillary lymph node dissection is unnecessary in the treatment of pure DCIS, but it is indicated when microinvasion is present. In these cases, sentinel lymph node biopsy may be an excellent alternative. In the NSABP B-24 trial, tamoxifen reduced both the invasive and non-invasive breast cancer events in either breast by 37%. Nearly all patients who develop a non-invasive recurrence following breast-sparing surgery are cured with mastectomy, and approximately 75% of those with an invasive recurrence are salvaged. Selected patients initially treated by lumpectomy alone may also undergo breast-conservation therapy at the time of relapse according to the same strict guidelines of tumor margin clearance required for the

  10. Correlation of E-cadherin expression with differentiation grade and histological type in breast carcinoma.

    PubMed Central

    Gamallo, C.; Palacios, J.; Suarez, A.; Pizarro, A.; Navarro, P.; Quintanilla, M.; Cano, A.

    1993-01-01

    Recently, a correlation has been suggested between a loss of E-cadherin (E-CD) and increased invasiveness of neoplastic cells. In this study, E-CD expression in breast cancer was investigated using an affinity-purified antibody (ECCD-2) in an immunoenzymatic (avidin-biotin-alkaline phosphatase) test. Intensity and extension of E-CD immunoreactivity were evaluated in 61 breast carcinomas and correlated with their histological type and grade, nodal involvement, and hormonal receptor status. Histological types were infiltrating ductal carcinoma of no special type (n = 54) and infiltrating lobular carcinoma (n = 7). All infiltrating ductal carcinomas of no special type except two grade 3 carcinomas showed positive immunoreactivity that was variable among different cases. Grade 1 breast carcinomas (n = 10) showed greater immunoreactivity than grade 2 (n = 25) and grade 3 (n = 19) carcinomas. E-CD immunoreactivity correlated positively with the degree of tubular formation and inversely with the mitoses number. None of the infiltrating lobular carcinomas expressed E-CD in their infiltrating cells, whereas they showed only weak immunostains in areas of atypical lobular hyperplasia and lobular carcinoma in situ. These results indicate that E-CD expression correlates with histological type and grade in breast carcinomas. Images Figure 1 Figure 2 Figure 3 PMID:7682767

  11. 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

  12. Hypofractionated Radiation Therapy for Breast Ductal Carcinoma In Situ

    SciTech Connect

    Hathout, Lara; Hijal, Tarek; Théberge, Valérie; Fortin, Bernard; Vulpe, Horia; Hogue, Jean-Charles; Lambert, Christine; Bahig, Houda; and others

    2013-12-01

    Purpose: Conventional radiation therapy (RT) administered in 25 fractions after breast-conserving surgery (BCS) is the standard treatment for ductal carcinoma in situ (DCIS) of the breast. Although accelerated hypofractionated regimens in 16 fractions have been shown to be equivalent to conventional RT for invasive breast cancer, few studies have reported results of using hypofractionated RT in DCIS. Methods and Materials: In this multicenter collaborative effort, we retrospectively reviewed the records of all women with DCIS at 3 institutions treated with BCS followed by hypofractionated whole-breast RT (WBRT) delivered in 16 fractions. Results: Between 2003 and 2010, 440 patients with DCIS underwent BCS followed by hypofractionated WBRT in 16 fractions for a total dose of 42.5 Gy (2.66 Gy per fraction). Boost RT to the surgical bed was given to 125 patients (28%) at a median dose of 10 Gy in 4 fractions (2.5 Gy per fraction). After a median follow-up time of 4.4 years, 14 patients had an ipsilateral local relapse, resulting in a local recurrence-free survival of 97% at 5 years. Positive surgical margins, high nuclear grade, age less than 50 years, and a premenopausal status were all statistically associated with an increased occurrence of local recurrence. Tumor hormone receptor status, use of adjuvant hormonal therapy, and administration of additional boost RT did not have an impact on local control in our cohort. On multivariate analysis, positive margins, premenopausal status, and nuclear grade 3 tumors had a statistically significant worse local control rate. Conclusions: Hypofractionated RT using 42.5 Gy in 16 fractions provides excellent local control for patients with DCIS undergoing BCS.

  13. Induction of Monocyte Chemoattractant Proteins in Macrophages via the Production of Granulocyte/Macrophage Colony-Stimulating Factor by Breast Cancer Cells

    PubMed Central

    Yoshimura, Teizo; Imamichi, Tomozumi; Weiss, Jonathan M.; Sato, Miwa; Li, Liangzhu; Matsukawa, Akihiro; Wang, Ji Ming

    2016-01-01

    Monocyte chemoattractant protein-1 (MCP-1)/CCL2 plays an important role in the initiation and progression of cancer. We previously reported that in 4T1 murine breast cancer, non-tumor stromal cells, including macrophages, were the major source of MCP-1. In the present study, we analyzed the potential mechanisms by which MCP-1 is upregulated in macrophages infiltrating 4T1 tumors. We found that cell-free culture supernatants of 4T1 cells (4T1-sup) markedly upregulated MCP-1 production by peritoneal inflammatory macrophages. 4T1-sup also upregulated other MCPs, such as MCP-3/CCL7 and MCP-5/CCL12, but modestly upregulated neutrophil chemotactic chemokines, such as KC/CXCL1 or MIP-2/CXCL2. Physicochemical analysis indicated that an approximately 2–3 kDa 4T1 cell product was responsible for the capacity of 4T1-sup to upregulate MCP-1 expression by macrophages. A neutralizing antibody against granulocyte/macrophage colony-stimulating factor (GM-CSF), but not macrophage CSF, almost completely abrogated MCP-1-inducing activity of 4T1-sup, and recombinant GM-CSF potently upregulated MCP-1 production by macrophages. The expression levels of GM-CSF in 4T1 tumors in vivo were higher than other tumors, such as Lewis lung carcinoma. Treatment of mice with anti-GM-CSF antibody significantly reduced the growth of 4T1 tumors at the injection sites but did not reduce MCP-1 production or lung metastasis in tumor-bearing mice. These results indicate that 4T1 cells have the capacity to directly upregulate MCP-1 production by macrophages by releasing GM-CSF; however, other mechanisms are also involved in increased MCP-1 levels in the 4T1 tumor microenvironment. PMID:26834744

  14. Expression of Neuroendocrine Markers in Different Molecular Subtypes of Breast Carcinoma

    PubMed Central

    Wachter, David L.; Hartmann, Arndt; Beckmann, Matthias W.; Fasching, Peter A.; Hein, Alexander; Bayer, Christian M.; Agaimy, Abbas

    2014-01-01

    Background. Carcinomas of the breast with neuroendocrine features are incorporated in the World Health Organization classification since 2003 and include well-differentiated neuroendocrine tumors, poorly differentiated neuroendocrine carcinomas/small cell carcinomas, and invasive breast carcinomas with neuroendocrine differentiation. Neuroendocrine differentiation is known to be more common in certain low-grade histologic special types and has been shown to mainly cluster to the molecular (intrinsic) luminal A subtype. Methods. We analyzed the frequency of neuroendocrine differentiation in different molecular subtypes of breast carcinomas of no histologic special type using immunohistochemical stains with specific neuroendocrine markers (chromogranin A and synaptophysin). Results. We found neuroendocrine differentiation in 20% of luminal B-like carcinomas using current WHO criteria (at least 50% of tumor cells positive for synaptophysin or chromogranin A). In contrast, no neuroendocrine differentiation was seen in luminal A-like, HER2 amplified and triple-negative carcinomas. Breast carcinomas with neuroendocrine differentiation presented with advanced stage disease and showed aggressive behavior. Conclusions. We conclude that neuroendocrine differentiation is more common than assumed in poorly differentiated luminal B-like carcinomas. Use of specific neuroendocrine markers is thus encouraged in this subtype to enhance detection of neuroendocrine differentiation and hence characterize the biological and therapeutic relevance of this finding in future studies. PMID:24701575

  15. Viral Therapy In Treating Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck Cancer or Metastatic Breast Cancer

    ClinicalTrials.gov

    2016-08-24

    Estrogen Receptor Negative; Estrogen Receptor Positive; Head and Neck Squamous Cell Carcinoma; HER2/Neu Negative; HER2/Neu Positive; Invasive Breast Carcinoma; Progesterone Receptor Negative; Progesterone Receptor Positive; Recurrent Head and Neck Carcinoma; Stage IV Breast Cancer; Triple-Negative Breast Carcinoma

  16. Sarcoma of bone following therapeutic irradiation for breast carcinoma

    SciTech Connect

    Doherty, M.A.; Rodger, A.; Langlands, A.O.

    1986-01-01

    Four patients with sarcoma arising in bone following therapeutic irradiation for breast carcinoma are presented, along with a review of the 40 patients who have been previously reported in the literature. The majority of these lesions arose in the scapula and the most frequently reported histology is osteosarcoma. The incidence of these lesions has been reported as 0.05% to 0.23% in three previous series. The average latent period between irradiation and the diagnosis of the sarcoma is 10.9 years with a range of 4.5-24 years. The average survival following diagnosis in this series was 2.4 months, which is comparable to other series. However, one patient treated by forequarter amputation and another treated by chemotherapy and radiotherapy survived 4 and 3 years, respectively.

  17. Metaplastic carcinoma of the right breast and simultaneous giant ovarian teratoma: a case report.

    PubMed

    Li, Shuang; Wei, Qing-Zhu

    2012-10-01

    We describe here a female patient who presented with a breast mass and giant abdominal mass. Fine needle aspiration cytology of the breast mass and histological examination after modified radical mastectomy confirmed metaplastic carcinoma of the breast. The epithelial components were formed by infiltrating ductal carcinoma with poor differentiation, and the sarcomatous components were formed by fibrosarcoma and osteosarcoma. Histological examination of the abdominal mass confirmed ovarian teratoma. The patient underwent modified radical mastectomy of the right breast and laparoscopic excision of the abdominal mass in the lower right quadrant. Having underwent six courses of chemotherapy, the patient is now in her tenth month after surgery and under follow-up, and she has no relapsed disease. These two diseases have never seen in one patient before. The case we report here provides some new data for research and clinical experience and it may also provide a new insight into the relationship between metaplastic breast carcinoma and ovarian teratoma. PMID:22854062

  18. Primary squamous cell carcinoma of the breast: a case report and review of literature

    PubMed Central

    Seddik, Youssef; Brahmi, Sami Aziz; Afqir, Said

    2015-01-01

    Primary squamous cell carcinoma is a well known malignancy of the skin and other organs composed of squamous cells, which are normally not found inside the breast. Therefore, a primary squamous cell carcinoma of the breast is an exceedingly uncommon phenomen and the management of this type of disease is still unclear. We report the case of a 43-year-old Moroccan woman, without significant medical history, presented an infected mass of 9 cm in the left breast associated with ipsilateral axillary lymphadenopathy. The mass's surgical biopsy revealed a triple negative primary squamous cell carcinoma of the breast. She underwent a neoadjuvant chemotherapy using 5 Fluoro-Uracil and platinum. After three courses, she presented a contralateral breast progression and apparition of metastasis at D10. She received one course of a palliative chemotherapy based on weekly paclitaxel stopped because of her peformans status deterioration. She died 7 months after her admission.

  19. Axillary lymph node tuberculosis masquerading as inflammatory breast carcinoma in an immune-compromised patient.

    PubMed

    Chikkannaiah, Panduranga; Vani, B R; Benachinmardi, Kirtilaxmi; Murthy, V Srinivasa

    2016-02-01

    While tuberculosis is still the leading opportunistic infection among human immunodeficiency virus-seropositive patients, extra-pulmonary tuberculosis is more common than pulmonary tuberculosis, with lymph nodes being a common site. Axillary lymph node pathology such as tuberculosis and lymphoma rarely mimics inflammatory breast carcinoma by producing lymphatic obstruction. We report a case of axillary lymph node tuberculosis in a 40-year-old immune-compromised woman, clinically presenting as inflammatory breast carcinoma. PMID:25681261

  20. Carcinoma erysipeloides as a presenting feature of breast carcinoma: A case report and brief review of literature

    PubMed Central

    Al Ameer, Ali; Imran, Maryam; Kaliyadan, Feroze; Chopra, Rajan

    2015-01-01

    Carcinoma erysipeloides (CE) is an uncommon but distinctive form of cutaneous metastasis that usually manifests clinically as a fixed erythematous patch or plaque resembling cellulitis or erysipelas. The inflamed area may show a distinct raised edge at the periphery and also edema secondary to lymphatic obstruction. Histologically, dense carcinoma cells in the dermal vascular channels and dense perivascular lymphocytic infiltrate may be seen. CE may rarely be the first sign of “silent” tumor of breast. We report a case of a 52-year-old married lady who presented with a three months history of pruritic erythematous patches over the left side of the breast that was resistant to all topical treatments and was diagnosed as erysipeloid breast carcinoma. PMID:26753138

  1. Triple‐negative breast carcinomas are a heterogeneous entity that differs between young and old patients

    PubMed Central

    Carvalho, Filomena M; Bacchi, Livia M; Santos, Priscila P C; Bacchi, Carlos E

    2010-01-01

    OBJECTIVE: To compare the frequency and immunohistochemical profiles of triple‐negative breast carcinomas in younger and older women. METHODS AND RESULTS: We selected patients diagnosed with triple‐negative breast carcinomas. The groups examined were women who were 35 years old or younger between 1997 and 2007 (n  =  74) and, for comparison, women who were 60 years old or older (n  =  19, consecutive cases). All formalin‐fixed and paraffin‐embedded tumor samples were reviewed and immunohistochemically stained for ER, PR, HER2, Ki‐67 antigen, epidermal growth factor receptor, cytokeratin 5/6, p53, vimentin, CD117, and p63 using tissue microarrays blocks. Triple‐negative breast carcinomas corresponded to 34.6% (74/213) of the carcinomas from the younger patients and 16.2% (19/117) of the carcinomas from the older patients (p  =  0.002). No significant differences in the frequency of the basal phenotype were observed in the two patient groups based on CK5/6 and/or epidermal growth factor receptor expression (74.3% vs. 68.4%). However, triple‐negative breast carcinomas in the older patients presented a higher frequency of CK5/6 expression compared to those of younger patients (42.1% vs. 9.6%; p  =  0.005), whereas triple‐negative breast carcinomas of younger patients had a higher expression level of epidermal growth factor receptor (71.6% vs. 47.3%). CONCLUSIONS: These results show that there were significant molecular differences between the triple‐negative basal‐like breast carcinomas that were diagnosed in younger women and those that were diagnosed in older women. These findings may provide a basis for describing the more aggressive phenotype of the triple‐negative breast carcinomas observed in younger women. PMID:21120307

  2. Evaluation of TNM Classification of Carcinoma of the Breast

    PubMed Central

    Sicher, K.; Waterhouse, J. A. H.

    1973-01-01

    A survey of the records of almost 2000 cases of carcinoma of the breast in the years 1960-67, since acceptance of the principles of the TNM system of classification, found only 9·2% lacking description. Although the TNM staging was not always allocated by the surgeon making the initial examination, the survey demonstrated that acceptance of the system has resulted in the inclusion of a much more detailed clinical description by the surgeon in the patient's record, from which it was generally possible to assess the TNM staging in the Radiotherapy Department. The more detailed survival rates available in the case of the TNM system, in comparison with the Manchester staging system, is cited as a further recommendation for its wider use. Although detailed localization of the tumour to subsites within the breast appears to have little influence on prognosis, the addition of a supplementary histological classification of node involvement is a valuable adjunct to the assessment of likely survival. PMID:4783159

  3. Export of microRNAs: A Bridge between Breast Carcinoma and Their Neighboring Cells

    PubMed Central

    Jahagirdar, Devashree; Purohit, Shruti; Jain, Aayushi; Sharma, Nilesh Kumar

    2016-01-01

    Breast cancer is a leading type of cancer among women in India as well as worldwide. According to the WHO 2015 report, it has been anticipated that there would be a twofold rise in the death due to breast cancer among women. The heterogeneous property of breast carcinoma has been suggested to be linked with dedicated set of communication and signaling pathway with their surroundings, which culminate into progression and development of the cancer. Among the plethora of communication tools in the hand of breast carcinoma cells is the recently appreciated exocytosis of the tightly packed short non-coding RNA molecules, predominantly the microRNAs (miRNAs). Recent studies suggest that miRNAs may work as courier messengers to participate in endocrine and paracrine signaling to facilitate information transfer between breast carcinoma and their neighboring cells. Evidence suggests that breast tumor cells communicate via packaged miRNAs in the tumor-released microvesicles, which enrich the tumor microenvironment. There is a strong view that dissecting out the mechanistic and regulatory aspects of miRNA export and role may uncover many prospects for overcoming the signaling defects and thereby controlling aberrant cell division. The detection of circulating miRNAs associated with breast carcinoma can also be used as biomarkers for early diagnosis. This review article is an attempt to provide updated knowledge on implications of short RNAs and their transport in the breast cancer pathophysiology. PMID:27379209

  4. Export of microRNAs: A Bridge between Breast Carcinoma and Their Neighboring Cells.

    PubMed

    Jahagirdar, Devashree; Purohit, Shruti; Jain, Aayushi; Sharma, Nilesh Kumar

    2016-01-01

    Breast cancer is a leading type of cancer among women in India as well as worldwide. According to the WHO 2015 report, it has been anticipated that there would be a twofold rise in the death due to breast cancer among women. The heterogeneous property of breast carcinoma has been suggested to be linked with dedicated set of communication and signaling pathway with their surroundings, which culminate into progression and development of the cancer. Among the plethora of communication tools in the hand of breast carcinoma cells is the recently appreciated exocytosis of the tightly packed short non-coding RNA molecules, predominantly the microRNAs (miRNAs). Recent studies suggest that miRNAs may work as courier messengers to participate in endocrine and paracrine signaling to facilitate information transfer between breast carcinoma and their neighboring cells. Evidence suggests that breast tumor cells communicate via packaged miRNAs in the tumor-released microvesicles, which enrich the tumor microenvironment. There is a strong view that dissecting out the mechanistic and regulatory aspects of miRNA export and role may uncover many prospects for overcoming the signaling defects and thereby controlling aberrant cell division. The detection of circulating miRNAs associated with breast carcinoma can also be used as biomarkers for early diagnosis. This review article is an attempt to provide updated knowledge on implications of short RNAs and their transport in the breast cancer pathophysiology. PMID:27379209

  5. Urachal adenocarcinoma that metastasized to breast was misinterpreted as primary breast mucinous carcinoma: A rare case report and literature review

    PubMed Central

    Zhao, Xiang-Rong; Gao, Chao; Zhang, Yong; Kong, Lei; Qu, Wei; Li, Jia; Gao, Yong-Sheng; Yu, Yong-Hua

    2016-01-01

    Abstract Background: The urachus is a vestigial tubular structure that connects the urinary bladder to the allantois during early embryonic development. Urachal carcinoma develops in the urachus, which is an embryological remnant of the urogenital sinus and allantois. The estimated annual incidence of urachal carcinoma in the general population is 0.01% of all cancers in adults. Moreover, urachal carcinoma accounts for 0.34% to 0.7% of all bladder carcinoma cases. And breast metastasis is extremely rarer. Methods and Results: A 42-year-old woman was admitted to our hospital with a palpable mass in the outer upper quadrant of the right breast, which was misinterpreted as a carcinoma that originated from the breast. Subsequently, she underwent surgery without any further meticulous examination. Immunohistochemistry analysis revealed positivity for CK20, Villin, and CDX-2 and negativity for CK7. After further inspection, a mass was found in the bladder dome using 18F-fluorodeoxyglucose positron emission tomography and computed tomography. The mass was surgically removed. Conclusion: Pathologic and immunohistochemical examination confirmed that the mass was urachal mucinous adenocarcinoma and mucinous adenocarcinoma to the right breast. The patient has been followed up without recurrence for 8 months. PMID:27583877

  6. Lipid-Rich Carcinoma of the Breast With Unusual Clinical and Histopathological Features.

    PubMed

    Gaspar, Balan Louis; Kumar, Mukin; Gupta, Rahul; Garg, Rashi; Singh, Rajinder; Vasishta, Rakesh Kumar

    2016-09-01

    Lipid-rich carcinoma of the breast is a rare form of invasive breast carcinoma of special type. Most cases are grade 3, hormone receptor negative, and associated with aggressive clinical behavior. We report an unusual case of lipid-rich carcinoma with morphological and immunophenotypical features different from those of cases reported so far in the literature. The index case underscores the fact that there is no consensus with regard to the exact nature of this tumor. Hence, larger studies are needed to draw meaningful conclusions. PMID:26920701

  7. Metaplastic Carcinoma of Breast with Extensive Chondroid Differentiation: A Case Report with Review of Literature

    PubMed Central

    Shrinivas, Teerthanath; Permi, Harish S; Kukreja, Prachi; Shetty, Jayaprakash

    2015-01-01

    Metaplastic carcinoma of breast (MBC) is a rare and aggressive type of invasive breast cancer. As it encompasses a variety of distinct histopathologic designations, diagnostic challenges abound. We present a case report of metaplastic carcinoma with extensive chondroid differentiation. This case merits presentation because of its rarity and difficulty to diagnose, especially if the tumour is composed mainly of sarcomatous elements. Standard chemotherapy regimes are ineffective against MBC. The prognosis of MBC is poor in comparison to classical invasive breast cancer. Data focusing on MBC is limited due to its rare incidence. PMID:26435956

  8. ABO blood groups in relation to breast carcinoma incidence and associated prognostic factors in Moroccan women.

    PubMed

    Zouine, S; Marnissi, F; Otmani, N; Bennani Othmani, M; El Wafi, M; Kojok, K; Zaid, Y; Tahiri Jouti, N; Habti, N

    2016-07-01

    The association between blood groups ABO and different types of diseases was established in several previous studies. Our aim was to seek the possible association between the ABO blood group and breast cancer-associated prognostic factors. The Chi-squared analytic test was used to compare phenotypic ABO distribution among Moroccan blood donors and 442 cases of women suffering from breast carcinoma with archived files in Maternity Ward of University Hospital C.H.U Ibn Rochd between 2008 and 2011. High incidence of breast carcinoma was observed in blood type B patients (p < 0.05). Blood type B was associated with breast carcinomas overexpressing human epidermal growth factor receptor HER2 (p < 0.05) and high risk of cancer at age over 70 years (p < 0.001). Blood type A was associated with high risk of cancer among women younger than 35 years old. Blood type A and AB were associated with high incidence of lymph node metastasis (p < 0.05). Multivariate analysis has shown correlation between O blood type and estrogen receptor-positive tumor. Patients with blood group A, B, and AB were more likely to develop aggressive breast carcinoma. Further follow-up studies are necessary to clarify the role of ABH antigens in the progression of breast carcinoma. PMID:27241035

  9. Left adrenal gland metastasis of breast invasive ductal carcinoma: A case report

    PubMed Central

    HE, TAO; LIU, JIAJU; LI, YIFAN; JIN, LU; SUN, SHUOLEI; NI, LIANGCHAO; MAO, XIANGMING; YANG, SHANGQI; LAI, YONGQING

    2016-01-01

    The majority of the metastatic lesions of the adrenal gland normally originate from lung cancer, colon malignant tumor, renal cell carcinoma and melanoma. However, adrenal gland metastasis that metastasize from breast invasive ductal carcinoma are extremely rare. The present study reported a rare case of left adrenal gland metastasis in a 35-year-old female who was diagnosed as breast carcinoma 5 years ago with a mass located on the left adrenal gland, which was detected during a routine examination. The patient was asymptomatic and adrenal gland computed tomography revealed a mass in the left adrenal gland. Definitive preoperative diagnosis failed to be established. Left adrenal gland laparoscopic adrenalectomy was performed and the diagnosis of adrenal gland metastasis of breast invasive ductal carcinoma was confirmed by pathological and immunohistochemical examination. The patient remained in good condition by the time of writing. PMID:27123296

  10. 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

  11. Unilateral indurated plaque in the axilla: a case of metastatic breast carcinoma.

    PubMed

    Shagalov, Devorah; Xu, Michelle; Liebman, Tracey; Taylor, Gina

    2016-01-01

    Breast cancer is the most commonly diagnosed cancer among American women and is also the most common internal malignancy to metastasize to the skin. Rarely, cutaneous metastases represent the first indication of breast carcinoma, putting dermatologists in an instrumental position to make the diagnosis of breast carcinoma. We report the case of a 71-year-old woman with a 10-year history of a slowly-enlarging, indurated plaque in the right axilla. Review of symptoms was significant only for occasional numbness and tingling that extended from the right axilla to the right hand. Biopsy revealed cells infiltrating in a single-file between the collagen bundles in the dermis and subcutis and immunohistochemical staining consistent with a diagnosis of invasive lobular carcinoma. Subsequent work up revealed a primary breast lesion and extensive bony metastases. PMID:27617728

  12. Tubular Carcinoma of the Breast: A Single Institution's Experience of a Favorable Prognosis.

    PubMed

    Boyan, William; Shea, Brian; Farr, Michael; Kohli, Manpreet; Ginalis, Ernest

    2016-06-01

    Tubular carcinoma is a subtype of invasive breast cancer that comprises 1 to 4 per cent of invasive breast cancers. Prior studies show nearly 100 per cent 15 year survival rate for tubular carcinoma compared to the 89.2 per cent five year survival of all breast cancers. These encouraging statistics beg the question should tubular cancers be treated as other invasive cancers, or can some patients be spared an invasive procedure or the side effects of adjuvant therapy? Fifty-seven cases of tubular carcinoma over 16 years were analyzed. All relevant aspects of the patient's history, treatment, and outcomes were documented. The aim was compare treatment outcomes of tubular breast cancer outcomes to that of all invasive breast cancers. Of the 57 patients, local recurrence was seen in two patients (3.5%) only one of which recurred as a tubular carcinoma (1.75%). There were no cancer-related mortalities. A look into our institution's data supported the notion that tubular carcinoma of the breast is a less aggressive histological type. Of our 57 cases, only two recurrences (3.5%) were noted and there were no cancer-related mortalities. Interestingly only one patient (1.75%) recurred as tubular carcinoma. Without controlling for adjuvant therapy, recommendations cannot be made for a less aggressive treatment plan at this point. Future randomized controlled trials may lead to a less aggressive treatment plan for this favorable subtype. On the basis of this study and others like it, physicians can give evidenced-based favorable prognosis with a diagnosis of tubular carcinoma of the breast. PMID:27305881

  13. Automated quantification of aligned collagen for human breast carcinoma prognosis

    PubMed Central

    Bredfeldt, Jeremy S.; Liu, Yuming; Conklin, Matthew W.; Keely, Patricia J.; Mackie, Thomas R.; Eliceiri, Kevin W.

    2014-01-01

    Background: Mortality in cancer patients is directly attributable to the ability of cancer cells to metastasize to distant sites from the primary tumor. This migration of tumor cells begins with a remodeling of the local tumor microenvironment, including changes to the extracellular matrix and the recruitment of stromal cells, both of which facilitate invasion of tumor cells into the bloodstream. In breast cancer, it has been proposed that the alignment of collagen fibers surrounding tumor epithelial cells can serve as a quantitative image-based biomarker for survival of invasive ductal carcinoma patients. Specific types of collagen alignment have been identified for their prognostic value and now these tumor associated collagen signatures (TACS) are central to several clinical specimen imaging trials. Here, we implement the semi-automated acquisition and analysis of this TACS candidate biomarker and demonstrate a protocol that will allow consistent scoring to be performed throughout large patient cohorts. Methods: Using large field of view high resolution microscopy techniques, image processing and supervised learning methods, we are able to quantify and score features of collagen fiber alignment with respect to adjacent tumor-stromal boundaries. Results: Our semi-automated technique produced scores that have statistically significant correlation with scores generated by a panel of three human observers. In addition, our system generated classification scores that accurately predicted survival in a cohort of 196 breast cancer patients. Feature rank analysis reveals that TACS positive fibers are more well-aligned with each other, are of generally lower density, and terminate within or near groups of epithelial cells at larger angles of interaction. Conclusion: These results demonstrate the utility of a supervised learning protocol for streamlining the analysis of collagen alignment with respect to tumor stromal boundaries. PMID:25250186

  14. High Resolution X-Ray Microangiography of 4T1 Tumor in Mouse Using Synchrotron Radiation

    SciTech Connect

    Sun Jianqi; Liu Ping; Gu Xiang; Liu Xiaoxia; Zhao Jun; Xiao Tiqiao; Xu, Lisa X.

    2010-07-23

    Angiogenesis is very important in tumor growth and metastasis. But in clinic, only vessels lager than 200 {mu}m in diameter, can be observed using conventional medical imaging. Synchrotron radiation (SR) phase contrast imaging, whose spatial resolution can reach as high as 1 {mu}m, has great advantages in imaging soft tissue structures, such as blood vessels and tumor tissues. In this paper, the morphology of newly formed micro-vessels in the mouse 4T1 tumor samples was firstly studied with contrast agent. Then, the angiogenesis in nude mice tumor window model was observed without contrast agent using the SR phase contrast imaging at the beamline for X-ray imaging and biomedical applications, Shanghai Synchrotron Radiation Facility (SSRF). The images of tumors showed dense, irregular and tortuous tumor micro-vessels with the smallest size of 20-30 {mu}m in diameter.

  15. Contralateral contiguous tuberculous lymphadenitis in a case of right breast carcinoma--Diagnostic dilemma.

    PubMed

    Mukhopadhyay, Tanmoy; Nandi, Moujhuri; Bhattacharya, Soumya; Khan, Enam Murshed

    2015-01-01

    Coexistence of tuberculosis (TB) in the breast or axillary lymph nodes with breast carcinoma though rare is not unknown. A 55-year-old woman presented with right axillary and left supraclavicular lymphadenopathies with no detectable lesion in either breasts or left axilla. Right axillary lymph node excision biopsy revealed metastatic adenocarcinoma. Diagnostic workup showed intense fluorodeoxyglucose (FDG)-avid lymph nodes on the left side neck at level V, supraclavicular, axillary, subpectoral and para-aortic regions, and low FDG activity in the right breast. Core biopsy of right breast lesion was reported as invasive ductal carcinoma and cytology of multiple left axillary lymphadenopathies as reactive hyperplasia. Excision biopsy of the supraclavicular lymph nodes unveiled the diagnosis of TB. She underwent right-modified radical mastectomy followed by external beam radiotherapy, has completed antituberculous treatment and is on follow-up. Extrapulmonary TB though uncommon; may be found in certain cases. Clinicians must be aware of its existence. PMID:26881597

  16. PIK3CA-AKT pathway mutations in micropapillary breast carcinoma.

    PubMed

    Flatley, Ellen; Ang, Daphne; Warrick, Andrea; Beadling, Carol; Corless, Christopher L; Troxell, Megan L

    2013-07-01

    Micropapillary carcinoma of the breast is associated with increased rates of lymph node metastasis and lymphovascular invasion. While activating point mutations in PIK3CA (encoding phosphatidylinositol-3-kinase catalytic subunit) or AKT1 are found in 25% to 30% of invasive ductal carcinomas, the mutational profile of invasive micropapillary carcinomas has not been characterized in detail. Micropapillary carcinomas, concurrent metastatic and precursor breast lesions from 19 patients were identified. Lesional tissue was punched from paraffin-tissue blocks, and genomic DNA was extracted and screened for a large panel of known hotspot mutations using multiplex polymerase chain reaction and mass-spectroscopy analysis (643 mutations in 53 genes). Hotspot point mutations were identified in 35% (7/20) of micropapillary breast carcinomas, including PIK3CA exons 7, 9 and 20 hotspots, as well as the AKT1 plekstrin homology domain mutation (E17K); mutations in TP53 and KRAS were each found in a single patient. In 6 patients, micropapillary and non-micropapillary components of the same tumor were separately tested, yielding concordant results in five; one had a wild type micropapillary component, but a PIK3CA mutation in the invasive ductal component. Concurrent lymph node metastases were mostly wild type (2/8 mutant). Accompanying ductal carcinoma in situ had point mutations in 45% (5/11), mostly concordant with invasive carcinoma; however, mutational status of other breast proliferative lesions was generally discordant with accompanying carcinoma. The rate of PIK3CA mutations in this series of micropapillary carcinomas is similar to invasive ductal carcinomas; however, there may be an enrichment of AKT1 mutations (10%). The non-micropapillary components and precursor lesions occasionally had different mutations. PMID:23352210

  17. Differentiating fibroadenoma and ductal carcinoma in situ from normal breast tissue by multiphoton microscopy

    NASA Astrophysics Data System (ADS)

    Nie, Yuting; Wu, Yan; Lian, Yuane; Fu, Fangmeng; Wang, Chuan; Chen, Jianxin

    2014-09-01

    Fibroadenoma (FA) is the most common benign tumor of the female breast and several studies have reported that women with it have increased risk of breast cancer. While the ductal carcinoma in situ (DCIS) is a very early form of breast cancer. Thus, early detections of FA and DCIS are critical for improving breast tumor outcome and survival. In this paper, we use multiphoton microscopy (MPM) to obtain the high-contrast images of fresh, unfixed, unstained human breast specimens (normal breast tissue, FA and DCIS). Our results show that MPM has the ability to identify the characteristics of FA and DCIS including changes of duct architecture and collagen morphology. These results are consistent with the histological results. With the advancement of MPM, the technique has potential ability to serve as a real-time noninvasive imaging tool for early detection of breast tumor.

  18. Metastatic Invasive Lobular Carcinoma of the Breast Masquerading as a Primary Renal Malignancy

    PubMed Central

    Al-Jarrah, Adil; Taranikanti, Varna; Sawhney, Sukhpal; Furrukh, Muhammad; Al-Hosni, Mohammad; Saparamadu, P. A. M.; De Silva, M. V. C.

    2013-01-01

    Breast cancer is known to metastasise to different organs in the body, but an initial presentation of breast cancer with loin pain secondary to a metastatic renal mass is extremely rare. We report a 58-year-old woman who presented with recurrent left loin pain due to a metastatic deposit of invasive lobular carcinoma of the breast. The detection of a renal mass on computed tomography led to the assumption of a renal pelvic malignancy. The diagnostic dilemma posed by the detection of a breast mass during staging and the usefulness of immunohistochemistry in the confirmation of diagnosis are discussed. PMID:23984034

  19. Mammaglobin-A immunohistochemistry in primary central nervous system neoplasms and intracranial metastatic breast carcinoma.

    PubMed

    Cimino, Patrick J; Perrin, Richard J

    2014-07-01

    Metastases represent the most common type of intracranial neoplasm. In women, 30% of such tumors derive from breast carcinoma. In neurosurgical cases with ambiguous cellular morphology and/or limited biopsy material, immunohistochemistry (IHC) is often performed to distinguish metastases from primary central nervous system (CNS) neoplasms. IHC for mammaglobin-A (MGA), a protein expressed in a majority of breast carcinomas, is commonly applied in this setting, but its utility for distinguishing primary CNS neoplasms from metastatic breast carcinoma is unknown; the reactivity of MGA in primary and metastatic CNS neoplasms has never been described. Here, we describe the frequency and patterns of IHC reactivity for MGA in metastatic and primary CNS neoplasms from patients with well-documented histories of breast carcinoma. Following a published protocol previously applied to non-CNS neoplasms, MGA staining of moderate to strong intensity within 5% or more of a neoplasm was considered positive. On the basis of these criteria, 3 of 12 (25.0%) glioblastomas, 1 of 10 (10.0%) meningiomas, and 47 of 95 (49.5%) metastases were positive. Importantly, the cytoarchitectural staining characteristics among all 4 MGA-positive primary CNS neoplasms (cytoplasmic and nuclear) differed from those of the metastases (cytoplasmic and membranous). These findings suggest that MGA IHC staining intensity and distribution can distinguish metastases from primary CNS neoplasms (P=0.0086) in women with a history of breast carcinoma but also indicate that cytologic staining patterns must be interpreted for more accurate tumor classification. PMID:23958549

  20. An Unusual Clinical Presentation of Gastrointestinal Metastasis From Invasive Lobular Carcinoma of Breast

    PubMed Central

    Balakrishnan, Bathmapriya; Shaik, Sufiya; Burman-Solovyeva, Irina

    2016-01-01

    Introduction. We present an unusual case of metastatic lobular breast carcinoma. Typical areas of metastasis include bone, gynecological organs, peritoneum, retroperitoneum, and gastrointestinal (GI) tract, in order of frequency. With regard to GI metastasis, extrahepatic represents a rare site. Case. Two years after being diagnosed with invasive lobular breast carcinoma, a 61-year-old female complained of 3 months of nonspecific abdominal pain and diarrhea. A colonoscopy revealed 5 tubular adenomatous polyps in the ascending and transverse colon. Contrast computed tomography (CT) of the abdomen and pelvis was done 7 months after the colonoscopy to further evaluate persistent diarrhea. The CT results were consistent with infectious or inflammatory enterocolitis. Despite conservative management, symptoms failed to improve and a repeat diagnostic colonoscopy was obtained. Random colonic biopsies revealed metastatic high-grade adenocarcinoma of the colon. Discussion. Metastatic lobular breast carcinoma to the GI tract can distort initial interpretation of endoscopic evaluation with lesions mimicking inflammation. The interval between discovery of GI metastasis and diagnosis of lobular breast cancer can vary widely from synchronous to 30 years; however, progression is most often much sooner. Nonspecific symptoms and subtle appearance of metastatic lesions may confound the diagnosis. A high index of suspicion is needed for possible metastatic spread to the GI tract in patients with a history of invasive lobular breast carcinoma. Perhaps, patients with nonspecific GI symptoms should have an endoscopic examination with multiple random biopsies as invasive lobular carcinoma typically mimics macroscopic changes consistent with colitis. PMID:27088099

  1. Autoantibodies to tailor-made panels of tumor-associated antigens in breast carcinoma.

    PubMed

    Piura, Ettie; Piura, Benjamin

    2011-01-01

    Autoantibodies (AAbs) to tumor-associated antigens (TAAs) have been identified in the sera of cancer patients. In a previous review published in this journal, we have focused on recent knowledge related to circulating AAbs to individual TAAs in breast carcinoma. This review will focus on recent knowledge related to AAb assays to tailor-made panels of TAAs in breast carcinoma. So far, AAb assays to the following tailor-made panels of TAAs have been assessed in breast carcinoma: (1) p53, c-myc, HER2, NY-ESO-1, BRCA2, and MUC1, (2) IMP1, p62, Koc, p53, c-MYC, cyclin B1, and survivin, (3) PPIA, PRDX2, FKBP52, HSP-60, and MUC1, (4) MUC1, HER2, p53, and IGFBP2, (5) p53, HER2, IGFBP-2, and TOPO2α, (6) survivin and livin, (7) ASB-9, SERAC1, and RELT, and (8) p16, p53, and c-myc. Assessment of serum AAbs to a tailor-made panel of TAAs provides better sensitivity to diagnosis of breast carcinoma than measuring serum AAbs to a single TAA. Nevertheless, measurement of serum AAbs to a panel of TAAs for screening and early diagnosis of breast carcinoma is still investigational and should be carried out along with traditional diagnostic studies. PMID:21423545

  2. Prognostic significance of TP53 alterations in breast carcinoma.

    PubMed Central

    Andersen, T. I.; Holm, R.; Nesland, J. M.; Heimdal, K. R.; Ottestad, L.; Børresen, A. L.

    1993-01-01

    Constant denaturant gel electrophoresis (CDGE) was used to screen 179 breast carcinomas for mutations in the conserved regions of the TP53 gene (exons 5 through 8). Mutations were found in 35 of 163 primary tumours (21%) and in 5 of 16 metastases (31%) and resided predominantly in exon 7. The majority of the mutations were G:C-->A:T transitions. Immunohistochemistry demonstrated nuclear accumulation of p53 protein in 35 of 162 primary tumours (22%) and in four of 15 metastases (27%). TP53 mutation was strongly associated with nuclear accumulation of p53 protein. In total 42 of 163 primary tumours (26%) and 5 of 16 metastases (31%) were demonstrated to contain TP53 alterations (mutation and/or nuclear protein accumulation). TP53 alteration in primary tumour was significantly associated with the following parameters: positive node status, T status > 1, negative oestrogen receptor status, negative progesterone receptor status, presence of ERBB2 gene amplification, and invasive ductal histology. Furthermore, there were statistically significant associations, independent of other prognostic factors, between TP53 alterations in primary tumour and disease-free and overall survival. Images Figure 1 Figure 2 PMID:8102535

  3. Primary ectopic breast carcinoma in a supernumerary breast arising in the anterior chest wall: a case report and review of the literature.

    PubMed

    Hallam, Sally; Aggarwal, Ajay; Predolac, Domonica; Cunnick, Giles; Ashford, Richard

    2013-01-01

    Accessory mammary tissue occurs in 0.2-6% of women, and is under the same hormonal influences as breast tissue, potentially undergoing malignant transformation. Carcinomas of accessory mammary tissue account for ∼0.3% of breast cancers, 5% of which are within a supernumerary breast. Due to its rarity and the low index of clinical suspicion, it is often diagnosed at a later stage compared with breast cancer. Reports of carcinoma developing in a supernumerary breast are rare. We describe a case of a 48-year-old woman, presenting with ectopic breast carcinoma within a supernumerary breast below the inframammary fold. We describe the mode of presentation, diagnosis and treatment with reference to the available literature. The radiotherapy treatment plan is discussed in detail to provide reference for future cases as the available literature offers no formal guidance on radiotherapy dose, fractionation or treatment field. PMID:24968437

  4. Clear Cell Carcinoma of the Breast: A Rare Breast Cancer Subtype – Case Report and Literature Review

    PubMed Central

    Ratti, Vilma; Pagani, Olivia

    2015-01-01

    Background Glycogen-rich clear cell breast carcinoma is a rare histological breast cancer subtype. Its prognosis may vary depending on specific clinical and pathological characteristics such as low grade, strong positivity of estrogen receptor (ER) expression and early diagnosis. Case Presentation We present the case of a 53-year-old woman with a bleeding 10-cm-diameter mass in the left breast. The histological examination showed a poorly differentiated tumor with malignant cells characterized by abundant clear cytoplasm. The diagnosis of clear cell carcinoma was based on the histological characteristics of the tumor, and a nonmammary origin was initially ruled out. The tumor was triple negative [i.e. ER, progesterone receptor (PR) and HER2 negative]. Four months after the initial locoregional treatment, the patient developed lung and distant lymph node metastases. Conclusions Glycogen-rich clear cell carcinoma of the breast is a rare tumor. Early diagnosis, absence of lymph node metastases and ER/PR positivity are associated with a better prognosis, as in other common breast cancer subtypes. PMID:26600782

  5. Carcinoma arising in microglandular adenosis of the breast: triple negative phenotype with variable morphology.

    PubMed

    Zhong, Fangfang; Bi, Rui; Yu, Baohua; Cheng, Yufan; Xu, Xiaoli; Shui, Ruohong; Yang, Wentao

    2014-01-01

    Carcinoma arising in microglandular adenosis (MGACA) is an extremely rare subtype of breast carcinoma. In this study, clinicopathological analysis of MGACA from 11 Chinese patients was conducted. Microscopically, all cases showed a spectrum of structure and glandular proliferations ranging from microglandular adenosis (MGA) to atypical MGA (AMGA) to MGACA. Carcinoma components were composed of high grade ductal carcinoma in situ (DCIS) in 1 case and invasive carcinoma in 10 cases. Invasive carcinomas were grade 3 in 10 tumors and grade 2 in 1. Invasive components in 5 of 10 cases were composed of invasive carcinoma of no special type (NST), and 1 case showed partially acinic cell differentiation. In 5 cases, invasive components were mixed of NST and matrix-producing carcinoma (MPC). All epitheliums in 11 cases were triple negative (ER-, PR-, HER2-), and diffuse positive for CK and S-100 protein. No myoepithelial cells were demonstrable from MGA to invasive components with immunohistochemical staining for P63 and calponin. PAS or reticulin stain showed the presence of a basement membrane around glands in MGA, AMGA, DCIS, and its absence in invasive components. Follow-up time ranged from 10 to 64 months. One patient developed a lung metastasis 24 months after surgery, 10 patients have been alive without recurrence. Our study revealed that MGACA is a distinct subset of breast carcinoma, with triple negative phenotype, high grade nuclear and variable morphology. Despite histopathologic and immunohistochemical features usually associated with a poor prognosis, MGACA seems to have a relatively favorable outcome. PMID:25337263

  6. Novel Mutations in Neuroendocrine Carcinoma of the Breast: Possible Therapeutic Targets.

    PubMed

    Ang, Daphne; Ballard, Morgan; Beadling, Carol; Warrick, Andrea; Schilling, Amy; O'Gara, Rebecca; Pukay, Marina; Neff, Tanaya L; West, Robert B; Corless, Christopher L; Troxell, Megan L

    2014-02-24

    Primary neuroendocrine carcinoma of the breast is a rare variant, accounting for only 2% to 5% of diagnosed breast cancers, and may have relatively aggressive behavior. Mutational profiling of invasive ductal breast cancers has yielded potential targets for directed cancer therapy, yet most studies have not included neuroendocrine carcinomas. In a tissue microarray screen, we found a 2.4% prevalence (9/372) of neuroendocrine breast carcinoma, including several with lobular morphology. We then screened primary or metastatic neuroendocrine breast carcinomas (excluding papillary and mucinous) for mutations in common cancer genes using polymerase chain reaction-mass spectroscopy (643 hotspot mutations across 53 genes), or semiconductor-based next-generation sequencing analysis (37 genes). Mutations were identified in 5 of 15 tumors, including 3 with PIK3CA exon 9 E542K mutations, 2 of which also harbored point mutations in FGFR family members (FGFR1 P126S, FGFR4 V550M). Single mutations were found in each of KDR (A1065T) and HRAS (G12A). PIK3CA mutations are common in other types of breast carcinoma. However, FGFR and RAS family mutations are exceedingly rare in the breast cancer literature. Likewise, activating mutations in the receptor tyrosine kinase KDR (VEGFR2) have been reported in angiosarcomas and non-small cell lung cancers; the KDR A1065T mutation is reported to be sensitive to VEGFR kinase inhibitors, and fibroblast growth factor receptor inhibitors are in trials. Our findings demonstrate the utility of broad-based genotyping in the study of rare tumors such as neuroendocrine breast cancer. PMID:24569783

  7. Novel mutations in neuroendocrine carcinoma of the breast: possible therapeutic targets.

    PubMed

    Ang, Daphne; Ballard, Morgan; Beadling, Carol; Warrick, Andrea; Schilling, Amy; O'Gara, Rebecca; Pukay, Marina; Neff, Tanaya L; West, Robert B; Corless, Christopher L; Troxell, Megan L

    2015-02-01

    Primary neuroendocrine carcinoma of the breast is a rare variant, accounting for only 2% to 5% of diagnosed breast cancers, and may have relatively aggressive behavior. Mutational profiling of invasive ductal breast cancers has yielded potential targets for directed cancer therapy, yet most studies have not included neuroendocrine carcinomas. In a tissue microarray screen, we found a 2.4% prevalence (9/372) of neuroendocrine breast carcinoma, including several with lobular morphology. We then screened primary or metastatic neuroendocrine breast carcinomas (excluding papillary and mucinous) for mutations in common cancer genes using polymerase chain reaction-mass spectroscopy (643 hotspot mutations across 53 genes), or semiconductor-based next-generation sequencing analysis (37 genes). Mutations were identified in 5 of 15 tumors, including 3 with PIK3CA exon 9 E542K mutations, 2 of which also harbored point mutations in FGFR family members (FGFR1 P126S, FGFR4 V550M). Single mutations were found in each of KDR (A1065T) and HRAS (G12A). PIK3CA mutations are common in other types of breast carcinoma. However, FGFR and RAS family mutations are exceedingly rare in the breast cancer literature. Likewise, activating mutations in the receptor tyrosine kinase KDR (VEGFR2) have been reported in angiosarcomas and non-small cell lung cancers; the KDR A1065T mutation is reported to be sensitive to VEGFR kinase inhibitors, and fibroblast growth factor receptor inhibitors are in trials. Our findings demonstrate the utility of broad-based genotyping in the study of rare tumors such as neuroendocrine breast cancer. PMID:25679062

  8. Biphasic papillary and lobular breast carcinoma with PIK3CA and IDH1 mutations.

    PubMed

    Ang, Daphne; VanSandt, Amanda M; Beadling, Carol; Warrick, Andrea; West, Robert B; Corless, Christopher L; Troxell, Megan L

    2012-12-01

    Morphologic "special types" of breast carcinomas have been recognized for many years, and their molecular and genetic properties have not been specifically studied until recently. Lobular carcinoma lacks functional E-cadherin expression but shares molecular similarities with low-grade invasive ductal carcinomas. Papillary carcinoma is relatively rare, and molecular features are just being elucidated. We report a case of concurrent invasive lobular and papillary carcinoma, the latter with extensive nodal involvement. Multiplex screening for activating point mutations identified different point mutations in the distinct morphologic components: lobular PIK3CA H1047R, papillary; PIK3CA Q546P, and IDH1 R132H. These molecular data favor coincidental "collision tumors" over clonal evolution. The IDH1 R132H point mutation is common in gliomas and acute myelogenous leukemia, but this has not been previously reported in breast carcinoma. The characterization of activating point mutations in morphologic special types of breast carcinoma may suggest avenues amenable to targeted therapy. PMID:23111200

  9. Pseudoangiomatous stromal hyperplasia: An observation on its microscopic involvement in breast carcinoma and the presence of lymph node metastases.

    PubMed

    Coyne, John D

    2010-09-01

    The spaces of pseudoangiomatous stromal hyperplasia (PASH) are postulated to be important in the intramammary spread of breast carcinoma. The present study aimed to note the prevalence of inconspicuous, microscopic foci of PASH (identified as CD34+ve, CD31-ve and D2-40-ve spaces containing tumour emboli) involved in breast carcinoma and to establish the significance of its relationship to lymph node metastases. A total of 80 cases of breast carcinoma were examined for microscopic foci of PASH permeated by carcinoma and, of the four cases found to demonstrate such involvement, three had lymph node metastases. PMID:22966384

  10. Investigation of Epstein-Barr virus in breast carcinomas in Tunisia.

    PubMed

    Hachana, Mohamed; Amara, Khaled; Ziadi, Sonia; Romdhane, Essia; Gacem, Riadh Ben; Trimeche, Mounir

    2011-11-15

    Breast carcinoma is a major cause of death among women, and the potential implication of viruses in its pathogenesis remains worth a hypothesis. The potential role of Epstein-Barr virus (EBV) in its pathogenesis is still a subject of continued discussion and investigation. The aim of this study was to evaluate the prevalence of EBV in sporadic breast cancers in Tunisia, and to determine the clinicopathological characteristics of virus-positive cases. Viral presence has been evaluated by polymerase chain reaction (PCR), in situ hybridization, and immunohistochemistry investigated on tumor tissues and their corresponding normal breast tissues collected from 123 Tunisian women with sporadic breast carcinomas. Viral status in tumors was then correlated with various clinicopathological parameters. Using specific PCR assays, EBV DNA was found in 33 (27%) out of 123 breast carcinoma cases. EBV-encoded small RNAs (EBERs) in situ hybridization was negative in the neoplastic cells, but stomal lymphocytes were positive in 4 cases. Immunohistochemistry for latent membrane protein 1 (LMP1) was negative in all cases. None of the normal breast tissues showed positive results for EBV using PCR, in situ hybridization, and immunohistochemistry. A correlation was found between EBV DNA presence and the negativity of estrogen receptor (P=0.008). However, no significant correlation was found for the other parameters investigated, including patient age, Scarff-Bloom-Richardson (SBR) histological grade, tumor size, and histological node involvement. With regard to survival data, overall and disease-free survivals were shorter in EBV-positive breast carcinoma cases than in EBV-negative ones, but this difference did not reach statistical significance. Our study indicates the presence of EBV DNA in a significant proportion of breast cancer in Tunisia. Further studies are required to elucidate the role of this virus in breast carcinogenesis. PMID:22024152

  11. Identification of the boundary between normal breast tissue and invasive ductal carcinoma during breast-conserving surgery using multiphoton microscopy

    NASA Astrophysics Data System (ADS)

    Deng, Tongxin; Nie, Yuting; Lian, Yuane; Wu, Yan; Fu, Fangmeng; Wang, Chuan; Zhuo, Shuangmu; Chen, Jianxin

    2014-11-01

    Breast-conserving surgery has become an important way of surgical treatment for breast cancer worldwide nowadays. Multiphoton microscopy (MPM) has the ability to noninvasively visualize tissue architectures at the cellular level using intrinsic fluorescent molecules in biological tissues without the need for fluorescent dye. In this study, MPM is used to image the microstructures of terminal duct lobular unit (TDLU), invasive ductal carcinoma and the boundary region between normal and cancerous breast tissues. Our study demonstrates that MPM has the ability to not only reveal the morphological changes of the cuboidal epithelium, basement membrane and interlobular stroma but also identify the boundary between normal breast tissue and invasive ductal carcinoma, which correspond well to the Hematoxylin and Eosin (H and E) images. Predictably, MPM can monitor surgical margins in real time and provide considerable accuracy for resection of breast cancerous tissues intraoperatively. With the development of miniature, real-time MPM imaging technology, MPM should have great application prospects during breast-conserving surgery.

  12. Metaplastic Breast Carcinoma Versus Triple-Negative Breast Cancer: Survival and Response to Treatment.

    PubMed

    Aydiner, Adnan; Sen, Fatma; Tambas, Makbule; Ciftci, Rumeysa; Eralp, Yesim; Saip, Pinar; Karanlik, Hasan; Fayda, Merdan; Kucucuk, Seden; Onder, Semen; Yavuz, Ekrem; Muslumanoglu, Mahmut; Igci, Abdullah

    2015-12-01

    Metaplastic breast carcinoma (MBC) differs from classic invasive ductal carcinomas regarding incidence, pathogenesis, and prognosis. The purpose of this study was to compare patients with MBC with clinicopathologic and treatment-matched patients with triple-negative breast carcinoma (TNBC) in terms of response to treatment, progression, and survival.Fifty-four patients with MBC and 51 with TNBC, who were treated at Istanbul University, Institute of Oncology, between 1993 and 2014, were included in the study. After correctly matching the patients with 1 of the 2 groups, they were compared to determine differences in response to treatment, disease progression, clinical course, and survival.At a median follow-up of 28 months, 18 patients (17.1%) died and 27 (25.5%) had disease progression. Metaplastic histology was significantly correlated with worse 3-year progression-free survival (PFS) (51 ± 9% vs. 82 ± 6%, P = 0.013) and overall survival (OS) (68 ± 8% vs. 94 ± 4%, P = 0.009) compared with TNBC histology. Patients who received taxane-based chemotherapy (CT) regimens or adjuvant radiotherapy had significantly better PFS (P = 0.002 and P < 0.001) and OS (P < 0.001 and P < 0.001) compared with others. In the multivariate analysis, MBC (hazard ratio [HR]: 0.09, P < 0.001), presence of neoadjuvant chemotherapy (NACT) (HR: 12.8, P = 0.05), and metastasis development at any time during the clinical course (HR: 38.7, P < 0.001) were significant factors that decreased PFS, whereas metastasis development was the only independent prognostic factor of OS (HR: 23.8, P = 0.009).MBC is significantly correlated with worse PFS and OS compared with TNBC. Patients with MBC are resistant to conventional CT agents, and more efficient treatment regimens are required. PMID:26717372

  13. A case of matrix-producing carcinoma of the breast with micoglandular adenosis and review of literature.

    PubMed

    Liu, Li-Yun; Sheng, Shu-Hai; Zhang, Zhi-Yong; Xu, Jin-Heng

    2015-01-01

    Matrix-producing carcinoma (MPC) of the breast is an extremely rare variant of metaplastic breast carcinoma that contains a mixture of epithelial and mesenchymal elements. As overt carcinoma with direct transition to a cartilaginous and/or osseous stromal matrix cells, MPC is of no spindle cells between those two elements. This is the case of a 43 year-old female patient with MPC which coexisted with microglandular adenosis (MGA), atypical MGA (AMGA) and carcinoma in situ arising in MGA (MGACA in situ). MGA is a rare, infiltrative, benign lesion of the breast with an indolent clinical course. Histological evidence of carcinoma arising from MGA has previously been documented. MPC arising in MGA is an extremely rare subtype of breast carcinoma and has been seldom detailed described in the previous studies. This report highlights one such case with cytomorphological and histopathological correlation, along with a review of pertinent literature and differential diagnosis. PMID:26339435

  14. Breast metastasis from signet ring cell carcinoma of the urinary bladder: A case report

    PubMed Central

    CHEN, YAOMIN; WEI, HAIYAN; LI, JUN; LIU, XIAOJIAO; FU, PEIFEN

    2016-01-01

    Carcinoma of the bladder metastatic to the breast is only sporadically reported in the literature. To the best of our knowledge, the present report is the first described case of signet ring cell carcinoma of the urinary bladder metastasizing to the breast. The patient was a 43-year-old woman who underwent transurethral partial cystectomy for signet ring cell carcinoma of the urinary bladder and adjuvant chemotherapy with cisplatin and gemcitabine. At 7 months postcystectomy, the patient presented with a solitary nodule in the right breast. Following transdermic core needle puncture biopsy of the lesion and histological examination, the tumor was found to be composed of signet ring cells, which were similar to the cells in the original cystectomy specimen. The patient underwent mastectomy without further chemotherapy and has remained free from metastasis to other organs during 1 year follow-up. PMID:27330778

  15. A recapitulative three-dimensional model of breast carcinoma requires perfusion for multi-week growth

    PubMed Central

    Goliwas, Kayla F; Marshall, Lauren E; Ransaw, Evette L; Berry, Joel L; Frost, Andra R

    2016-01-01

    Breast carcinomas are complex, three-dimensional tissues composed of cancer epithelial cells and stromal components, including fibroblasts and extracellular matrix. In vitro models that more faithfully recapitulate this dimensionality and stromal microenvironment should more accurately elucidate the processes driving carcinogenesis, tumor progression, and therapeutic response. Herein, novel in vitro breast carcinoma surrogates, distinguished by a relevant dimensionality and stromal microenvironment, are described and characterized. A perfusion bioreactor system was used to deliver medium to surrogates containing engineered microchannels and the effects of perfusion, medium composition, and the method of cell incorporation and density of initial cell seeding on the growth and morphology of surrogates were assessed. Perfused surrogates demonstrated significantly greater cell density and proliferation and were more histologically recapitulative of human breast carcinoma than surrogates maintained without perfusion. Although other parameters of the surrogate system, such as medium composition and cell seeding density, affected cell growth, perfusion was the most influential parameter. PMID:27516850

  16. A recapitulative three-dimensional model of breast carcinoma requires perfusion for multi-week growth.

    PubMed

    Goliwas, Kayla F; Marshall, Lauren E; Ransaw, Evette L; Berry, Joel L; Frost, Andra R

    2016-01-01

    Breast carcinomas are complex, three-dimensional tissues composed of cancer epithelial cells and stromal components, including fibroblasts and extracellular matrix. In vitro models that more faithfully recapitulate this dimensionality and stromal microenvironment should more accurately elucidate the processes driving carcinogenesis, tumor progression, and therapeutic response. Herein, novel in vitro breast carcinoma surrogates, distinguished by a relevant dimensionality and stromal microenvironment, are described and characterized. A perfusion bioreactor system was used to deliver medium to surrogates containing engineered microchannels and the effects of perfusion, medium composition, and the method of cell incorporation and density of initial cell seeding on the growth and morphology of surrogates were assessed. Perfused surrogates demonstrated significantly greater cell density and proliferation and were more histologically recapitulative of human breast carcinoma than surrogates maintained without perfusion. Although other parameters of the surrogate system, such as medium composition and cell seeding density, affected cell growth, perfusion was the most influential parameter. PMID:27516850

  17. Establishment of two new cell lines derived from human breast carcinomas with HER-2/neu amplification.

    PubMed Central

    Meltzer, P.; Leibovitz, A.; Dalton, W.; Villar, H.; Kute, T.; Davis, J.; Nagle, R.; Trent, J.

    1991-01-01

    Two human cell lines (UACC-812 and 893), both containing significant amplification of the HER-2/neu gene, were established from biopsy specimens of breast carcinomas. One patient had Stage II breast carcinoma; the other had metastatic disease. Characterisation of these lines has revealed that both are highly aneuploid containing multiple clonal chromosome alterations, have doubling times near 100 h, and are oestrogen and progesterone receptor negative. Electron microscopy demonstrates that both lines contain numerous microvilli, cytoplasmic filaments, multivesicular bodies, and desmosomes. Immunoblot analysis for P-glycoprotein using the monoclonal antibody C219 was negative for both patient cell lines. These relatively rare cell lines may represent a useful model to investigate human breast carcinomas. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:1674877

  18. Synchronous bilateral primary breast malignant phyllodes tumor and carcinoma of the breast with Paget’s disease: a case report and review of the literature

    PubMed Central

    Zhao, Hongyuan; Cheng, Xiaoming; Sun, Suhong; Yang, Weiming; Kong, Fanli; Zeng, Feng

    2015-01-01

    Synchronous bilateral primary breast malignant phyllodes tumor or/and carcinoma of the breast with Paget’s disease is rare. In the article, we present a case of bilateral carcinoma of the breast with Paget’s disease of the right breast and malignant phyllodes tumor of the left breast. A 44-years-old Chinese woman presented with a 1 month history of the right breast nipple with eczema and fester and growing and palpable mass of left breast. Molybdenum target X-ray revealed microcalcification in the right breast, which was highly suspected of malignant tumor, and round-like mass with smooth surface and homogeneous density in the left breast. Color ultrasound showed a lobulated lump which circumferential blood flows around in the left breast, and which did not show any mass in the right breast. The patient was undertaken the bilateral modified radical mastectomy. The histological diagnosis was Paget’s disease associated with infiltrating ductal carcinoma in the right breast and malignant phyllodes tumor the left breast. The patient also received 6 cycles of the postoperative adjuvant chemotherapy by using T.T. regimen comprised docetaxel (100 mg) and pirarubicin (60 mg). PMID:26770378

  19. Clinical pathology of metastatic gastric carcinoma to the breast: A report of two cases and a review of literature

    PubMed Central

    TIAN, QIUHONG; ZENG, JINSHENG; TAO, XUEQIN; ZHANG, ZHANMIN; ZHOU, XIAODONG; WANG, YITING

    2016-01-01

    The breast is an unusual site for metastasis from a gastric carcinoma. The present study reports two cases of metastatic gastric carcinoma to the breast. The first patient, a 37-year-old woman, initially presented with gastric adenocarcinoma, prior to developing metastatic cancer to the breast 4 years later. The second female patient presented with a breast mass, and a modified radical mastectomy was performed; however, the subsequent pathological examination revealed the mass to be a metastatic signet ring cell carcinoma. An abdominal computed tomography scan revealed a diffuse gastric wall thickening that was consistent with gastric cancer. The findings suggest that immunohistochemistry is a useful tool to differentiate between primary breast tumors and gastrointestinal carcinomas that have metastasized to the breast. Additional studies are required in order to define the optimal treatment. PMID:27123067

  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. Comparison of metastatic neuroendocrine neoplasms to the breast and primary invasive mammary carcinomas with neuroendocrine differentiation.

    PubMed

    Mohanty, Sambit K; Kim, Stacey A; DeLair, Deborah F; Bose, Shikha; Laury, Anna R; Chopra, Shefali; Mertens, Richard B; Dhall, Deepti

    2016-08-01

    Metastatic neuroendocrine neoplasms to the breast may show considerable morphologic overlap with primary mammary carcinomas, particularly those showing evidence of neuroendocrine differentiation, and may be misdiagnosed as such. Accurate distinction between these two entities is crucial for determination of appropriate clinical management. The histologic and immunohistochemical features of metastatic neuroendocrine neoplasms to the breast were studied and compared with the features of primary invasive mammary carcinomas with neuroendocrine differentiation, which served as controls. Of the metastatic neuroendocrine neoplasms, 15 were well-differentiated neuroendocrine tumors with carcinoid tumor-type morphology and 7 were poorly differentiated/high-grade neuroendocrine carcinomas with small-cell or large-cell neuroendocrine carcinoma morphology. The majority of the metastatic neoplasms originated in the lung and gastrointestinal tract. There were histologic similarities between metastatic neuroendocrine neoplasms and invasive mammary carcinomas with neuroendocrine differentiation, both of which exhibited neuroendocrine histologic features (nested and trabecular architecture, minimal tubular differentiation, and characteristic nuclear features). Only one case of the invasive mammary carcinomas with neuroendocrine differentiation was modified Bloom-Richardson grade 1 (largely due to minimal tubular differentiation on most such tumors), and the invasive mammary carcinomas with neuroendocrine differentiation were often associated with in situ carcinoma. Immunohistochemistry was helpful in distinguishing metastatic neuroendocrine neoplasms from invasive mammary carcinomas with neuroendocrine differentiation. Whereas the majority of invasive mammary carcinomas with neuroendocrine differentiation were positive for estrogen receptor and GATA3, metastatic neuroendocrine neoplasms were typically negative for estrogen receptor and GATA3, and metastatic well

  2. CHANGES IN CpG ISLANDS METHYLATION PATTERNS DURING DUCTAL BREAST CARCINOMA PROGRESSION

    PubMed Central

    Hoque, Mohammad Obaidul; Prencipe, Maria; Poeta, Maria Luana; Valori, Vanna Maria; Gallo, Antonietta Pia; Ostrow, Kimberly; Bonghi, Loriana; Vitale, Rita; Maiello, Evaristo; Apicella, Adolfo; Rossiello, Raffaele; Zito, Francesco; Stefania, Tommasi; Paradiso, Angelo; Schittulli, Francesco; Carella, Massimo; Dallapiccola, Bruno; Murgo, Roberto; Carosi, Illuminato; Bisceglia, Michele; Fazio, Vito Michele; Sidransky, David; Parrella, Paola

    2013-01-01

    CpG island hypermethylation is emerging as one of the main mechanisms for inactivation of cancer related genes in breast tumorigenesis. We examined the changes in methylation patterns during ductal breast cancer progression from atypical ductal hyperplasia to in situ and invasive carcinoma. Paired samples of synchronous pre invasive lesions (Atypical Ductal Hyperplasia and/or Ductal Carcinoma in situ) and invasive ductal breast carcinoma from 31 patients, together with isolated lesions from additional 24 patients were studied. Overall, 95 pathological samples and 20 normal breast tissues were analyzed by Quantitative Methylation Specific PCR (QMSP) on a panel of 9 gene promoters (ESR1, APC, CDH1, CTNNB1, GSTPI, THBS1, MGMT, TMS1 and TIMP3). APC, CDH1, and CTNNB1 promoter regions showed an increase in frequency of methylation and increased methylation levels in pathological samples when compared with normal breast tissues. The analysis of the syncronous paired breast lesions demonstrated also an increase in methylation frequency and level for APC, CDH1, and CTNNB1 genes during progression. By establishing a cutoff value, we were able to distinguish among -invasive and invasive lesions. Synchronous methylation of APC, CDH1, and CTNNB1 was associated only with invasive lesions, whereas simultaneous methylation of APC and CDH1 or APC and CTNNB1 were more frequent in ductal carcinoma in situ and invasive carcinoma. Our data point to direct involvement of APC, CDH1, and CTNNB1 CpG island promoter methylation in the early stages of breast cancer progression, and suggest that these molecular alterations might be involved in the transition to an invasive phenotype. PMID:19789364

  3. Chromogranin-reactive endocrine cells in argyrophilic carcinomas ("carcinoids") and normal tissue of the breast.

    PubMed Central

    Bussolati, G.; Gugliotta, P.; Sapino, A.; Eusebi, V.; Lloyd, R. V.

    1985-01-01

    Breast carcinomas, either positive or negative with the Grimelius' silver procedure, benign fibroadenomas, duct papillomas, and areas of histologically normal breast tissue were tested immunocytochemically with the mouse monoclonal antibody LK2H10 directed against human chromogranin. This is regarded as a general stain for polypeptide-hormone-producing cells and tumors. In 3 of the 9 cases of argyrophilic carcinoma, but in none of 12 ductal infiltrating carcinomas, chromogranin-positive cells were found: the number of reactive cells was very low in 1 case, while in the other 2 carcinomas about 50% of the argyrophilic cells appeared stained. In areas of histologically normal breast tissue, rare argyrophilic chromogranin-positive cells were detected. This study is the first reported evidence concerning the presence of endocrinelike cells probably belonging to the diffuse neuroendocrine system in the normal mammary parenchyma. Our data are consistent with the endocrine nature of at least some of the breast argyrophilic carcinomas. Images Figure 1 Figure 2 Figures 3 and 4 Figure 5 Figure 6 PMID:4025508

  4. Pseudoangiomatous stromal hyperplasia (PASH) tumour at the surgical scar site in a patient of carcinoma breast.

    PubMed

    Abrari, Andleeb

    2011-01-01

    A patient on follow-up post surgery for carcinoma breast, presented with a nodule under the surgical scar. The sinister eventuality of recurrent carcinoma was clinically considered first. The lesion was biopsied and the histopathology was diagnostic of pseudoangiomatous stromal hyperplasia tumour. The nodule was excised and the patient's clinical denouement has been uneventful in the 4 months which have elapsed after this event. PMID:22688488

  5. Vulvar melanoma and endometrial polyp following breast carcinoma: a case report.

    PubMed

    Shen, L; Zeng, F; Hong, L; Zhang, G; Mai, R

    2013-01-01

    The authors describe the occurrence of a 55-year-old female patient presenting with a vulvar melanoma, endometrial polyp, and a prior history of breast carcinoma excised from the left chest wall, radiotherapy, chemotherapy, and tamoxifen maintenance for two years. This case exemplified second primary vulvar melanoma following breast cancer and supported that radiotherapy might play a role in the onset of secondary cancer. This case report also emphasizes the onset of endometrial polyp induced by tamoxifen. PMID:23781599

  6. Synchronous ipsilateral carcinoma of the accessory mammary gland and primary lymphoma of the breast with subsequent rectal carcinoma: report of a case.

    PubMed

    Nishikawa, Akihiro; Kasai, Hide; Koyama, Yoshinori; Koide, Naohiko; Iijima, Akihiro; Shimojo, Hisashi; Kumeda, Shigeyoshi

    2014-01-01

    A case of synchronous carcinoma of the accessory mammary gland and primary breast lymphoma with subsequent rectal carcinoma has not been reported previously. We present a very rare case of primary non-Hodgkin lymphoma of the left breast diagnosed simultaneously with invasive lobular carcinoma of the left axillary accessory mammary gland and rectal adenocarcinoma. An 82-year-old Japanese woman presented with two palpable masses on the left chest wall. She was given a diagnosis of suspected breast malignant tumor and axillary accessory mammary gland. She underwent excision of the axillary accessory mammary gland and left mastectomy with axillary lymph node dissection. Histopathological examination revealed diffuse large B-cell lymphoma of the breast and invasive lobular carcinoma of the axillary accessory mammary gland with lymph nodes metastasis. Three months after the surgery, primary rectal adenocarcinoma was also detected by F-18 fluorodeoxyglucose positron emission tomography. Hartmann's operation was performed, since which time the patient has been doing well. PMID:25217973

  7. Breast ductal carcinoma and metastatic lymphoma to the contralateral breast in patient with cutaneous non-Hodgkin lymphoma

    PubMed Central

    Di Nubila, B; Meroni, S; Bonello, L; Peccatori, F; Cassano, E; Bellomi, M

    2011-01-01

    Breast lymphoma is a rare condition, both as a primary and a metastatic manifestation. The primary form has an incidence ranging from 0.04% to 0.5% of all breast neoplasms, whereas the metastatic form has an incidence of 0.07%. We hereby report a clinical case of a patient who presented with cutaneous non-Hodgkin lymphoma (NHL) in the left scapulohumeral region treated with surgery followed by radiotherapy (40 Gy total). Three years following radiotherapy, the patient was diagnosed with a left breast infiltrating ductal carcinoma, treated with conservative surgery and adjuvant therapy. The following year, i.e. four years after the initial diagnosis of NHL, two lymphoproliferative relapses occurred: in the left cutaneous scapulohumeral region at the original site of disease, and in the right breast. The aim of this paper is to highlight an uncommon oncologic disorder such as breast lymphoma, highlighting its clinical and radiological manifestations. Some studies reported a possible aetiological role of radiotherapy in the development of breast cancer following treatment of NHL, and in the development of breast cancer following treatment of Hodgkin lymphoma, which could potentially explain our findings. PMID:21607043

  8. 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

  9. 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

  10. 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

  11. In situ clinical evidence that zinc levels are decreased in breast invasive ductal carcinoma

    PubMed Central

    Zou, Jing; Franklin, Renty B.

    2016-01-01

    Purpose Altered zinc levels in malignant cells versus their normal cells have important implications in the development and progression of several cancers. Prostate, pancreatic, and hepatocellular carcinomas exhibit consistent marked zinc decrease in situ in the malignant cells, and other cancers (such as kidney, lung, and thyroid) also exhibit decreased tissue zinc levels. However, zinc levels are increased in breast cancer tissue compared to breast normal tissue, and the contemporary dominant view is that zinc is increased in invasive ductal carcinoma. This has important implications regarding the role and effects of zinc in breast malignancy compared to other cancers, which caused us to initiate this study to either confirm or challenge the contemporary view of an increased zinc level in the invasive ductal malignant cells. Methods We employed dithizone staining of breast tissue sections and tissue cores to determine the relative in situ cellular zinc levels specifically in the invasive ductal malignant cells as compared to normal ductal epithelium. This approach had not been employed in any of the reported breast studies. Results The results revealed that the zinc levels are consistently and markedly decreased in the ductal malignant cells as compared with higher prominent zinc levels in the normal ductal epithelium. Decreased zinc is evident in Grade 1 well-differentiated malignancy and in Grade 2 and Grade 3 carcinomas. Among the twenty-five cancer cases in this study, none exhibited increased zinc in the invasive ductal carcinoma compared to the zinc level in the normal ductal epithelium. Conclusions The decreased zinc levels in breast invasive ductal carcinoma is consistent with prostate, pancreatic, and liver carcinomas in which the decrease in zinc is a required event in the development of malignancy to prevent cytotoxicity that would result from the higher zinc levels in the normal cells. This new understanding requires a redirection in elucidating the

  12. Preparation and Analysis of In Vitro Three Dimensional Breast Carcinoma Surrogates.

    PubMed

    Goliwas, Kayla F; Miller, Lindsay M; Marshall, Lauren E; Berry, Joel L; Frost, Andra R

    2016-01-01

    Three dimensional (3D) culture is a more physiologically relevant method to model cell behavior in vitro than two dimensional culture. Carcinomas, including breast carcinomas, are complex 3D tissues composed of cancer epithelial cells and stromal components, including fibroblasts and extracellular matrix (ECM). Yet most in vitro models of breast carcinoma consist only of cancer epithelial cells, omitting the stroma and, therefore, the 3D architecture of a tumor in vivo. Appropriate 3D modeling of carcinoma is important for accurate understanding of tumor biology, behavior, and response to therapy. However, the duration of culture and volume of 3D models is limited by the availability of oxygen and nutrients within the culture. Herein, we demonstrate a method in which breast carcinoma epithelial cells and stromal fibroblasts are incorporated into ECM to generate a 3D breast cancer surrogate that includes stroma and can be cultured as a solid 3D structure or by using a perfusion bioreactor system to deliver oxygen and nutrients. Following setup and an initial growth period, surrogates can be used for preclinical drug testing. Alternatively, the cellular and matrix components of the surrogate can be modified to address a variety of biological questions. After culture, surrogates are fixed and processed to paraffin, in a manner similar to the handling of clinical breast carcinoma specimens, for evaluation of parameters of interest. The evaluation of one such parameter, the density of cells present, is explained, where ImageJ and CellProfiler image analysis software systems are applied to photomicrographs of histologic sections of surrogates to quantify the number of nucleated cells per area. This can be used as an indicator of the change in cell number over time or the change in cell number resulting from varying growth conditions and treatments. PMID:27214165

  13. 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

  14. Dysregulated expression of adamalysin-thrombospondin genes in human breast carcinoma.

    PubMed

    Porter, Sarah; Scott, Stuart D; Sassoon, Elaine M; Williams, Mark R; Jones, J Louise; Girling, Anne C; Ball, Richard Y; Edwards, Dylan R

    2004-04-01

    The adamalysin-thrombospondin (ADAMTS) proteinases are a relatively newly described branch of the metzincin family that contain metalloproteinase, disintegrin, and thrombospondin motifs. They have been implicated in various cellular events, including cleavage of proteoglycans, extracellular matrix degradation, inhibition of angiogenesis, gonadal development, and organogenesis. However, in many cases, their normal physiological roles and their potential for dysregulation in malignancy remain to be established. The expression profile of ADAMTS1-20 in human breast carcinoma was undertaken by real-time PCR using RNA isolated from malignant tumors, nonneoplastic mammary tissue, and breast cancer cell lines to identify altered regulation that may have potential pathogenetic and prognostic significance. Our studies show that seven of the ADAMTS genes (ADAMTS1, 3, 5, 8, 9, 10, and 18) are consistently down-regulated in breast carcinomas with respect to nonneoplastic mammary tissue, irrespective of the heterogeneity of the samples and the tumor type or grade (Mann-Whitney U test, P < 0.0001 for each gene). Conversely, ADAMTS4, 6, 14, and 20 are consistently up-regulated in breast carcinomas (P = 0.005, P < 0.0001, P = 0.003, and P = 0.001, respectively). ADAMTS2, 7, 12, 13, 15, 16, 17, and 19 show no significant difference between the sample types. ADAMTS1, 2, 7, 8, 10, and 12 are expressed predominantly in stromal fibroblasts. ADAMTS3, 4, 5, 6, 9, and 13-20 inclusive are expressed predominantly in myoepithelial cells; all appear to be relatively poorly expressed in luminal epithelial cells. ADAMTS15 has emerged as being an independent predictor of survival, with RNA expression levels significantly lower (P = 0.007) in grade 3 breast carcinoma compared with grade 1 and 2 breast carcinoma. PMID:15073121

  15. Iodine-131 in breast milk following therapy for thyroid carcinoma

    SciTech Connect

    Robinson, P.S.; Barker, P.; Campbell, A.

    1994-11-01

    This study evaluates breast milk secretion of {sup 131}I following therapeutic adminstration of 4000 MBq of {sup 131}I-iodide during lactation. Breast milk {sup 131}I activity concentration was measured over a 32-day period. Dosimetry calculations were undertaken to estimate the period for discontinuation of breast feeding and the equivalent dose to the breasts. To achieve an infant effective dose <1 mSv and an infant thyroid dose <10 mSv, breast feeding would need to be discontinued for at least 52 days. The estimated equivalent dose to the breasts was 1.6 Gy. It is suggested that {sup 131}I-iodide adminstration is not undertaken during lactation and that breast feeding is discontinued several days prior to administration. 26 refs., 2 figs., 2 tabs.

  16. Secondary Metastasis to the Mandible From Breast Carcinoma -A Rare Case Report.

    PubMed

    Thorawat, Amit; Naikmasur, Venkatesh G; Patil, Preeti; Perumal, Priya

    2015-07-01

    Regardless of the rare occurrence of metastatic lesions to the jaw, it should be taken into consideration in the individuals with a history of malignancy. Early detection requires accurate examination, and microscopic evaluation is essential. In this paper we report a case of breast carcinoma to the mandible as female breast cancer is the most frequent metastatic lesion to the mandible and its metastasis is well documented. The patient's medical history revealed that she had undergone mastectomy on the left breast three years ago. As this condition is infrequently described, documentation of new cases will augment the existing knowledge. PMID:26393225

  17. Anal metastasis as the sentinel and isolated presentation of invasive ductal breast carcinoma.

    PubMed

    Rengifo, C; Titi, S; Walls, J

    2016-05-01

    Breast cancer currently affects 1 in 8 women in the UK during their lifetime. Common sites for breast cancer metastasis include the axillary lymph nodes, bones, lung, liver, brain, soft tissue and adrenal glands. There is well documented evidence detailing breast metastasis to the gastrointestinal tract but anal metastasis is exceptionally rare. We present the case of a 78-year-old woman with an anal metastasis as the sentinel and isolated presentation of an invasive ductal breast carcinoma. As advances in the treatment of breast cancer improve, and with an ageing and expanding population, there will be an increasing number of cancer survivors, and more of these unusual presentations may be encountered in the future. PMID:27087339

  18. Comparative single cell and flow DNA analysis in aspiration biopsies from breast carcinomas.

    PubMed

    Auer, G; Tribukait, B

    1980-11-01

    The DNA distribution patterns in fine needle aspirates from 17 breast carcinomas was analysed, using single cell and flow cytophotometric techniques. A good correlation was observed to exist between the modal DNA values obtained by the two methods. Advantages and disadvantages of the two methods are discussed. PMID:7010915

  19. Robinson's cytological grading on aspirates of breast carcinoma: Correlation with Bloom Richardson's histological grading

    PubMed Central

    Sinha, SK; Sinha, Namita; Bandyopadhyay, Ranjana; Mondal, Santosh K

    2009-01-01

    Background: Cytological grading (CG) on aspirates of breast carcinoma is a useful tool for surgical maneuver and prognosis. Aims: An endeavor was made to use CG on aspirates of breast carcinoma using Robinson's grade and to correlate it with Bloom Richardsons’ histopathological grading. Materials and Methods: A total of 59 patients of breast carcinoma, aged 28-57 years, were aspirated and the smears were graded using Robinson's criteria. All the cases were correlated with Bloom Richardson's grade on histopathology in mastectomy specimens. Lymphadenopathy in 38 cases was aspirated and stained with Papanicolaou and Romanowsky stain. Results: Robinson's CG correlated well with Bloom Richardson's histopathological grading. For grade I and II tumors, there was substantial strength of agreement between cytology and histopathology, while in grade III, the concordance was nearly perfect. Lymph node metastasis was found in 27 of 32 axillary nodes, three of five cervical nodes and the only palpable supraclavicular node. Lymph node metastasis was observed in three with cytological grade II, 28 of grade III and none of grade I. All grade I had stage A, two of grade II had stage B, while all grade III had either stage B or stage C disease. Conclusions: Thus, CG of breast carcinoma correlates well with histopathological grading and may well be useful as a prognostic marker. PMID:21938177

  20. Clinical-Pathologic Features and Long-Term Outcomes of Tubular Carcinoma of the Breast Compared With Invasive Ductal Carcinoma Treated With Breast Conservation Therapy

    SciTech Connect

    Liu, Gene-Fu F.; Yang Qifeng; Haffty, Bruce G.; Moran, Meena S.

    2009-12-01

    Purpose: To evaluate our institutional experience of treating tubular carcinoma of the breast (TC) and invasive ductal carcinoma (IDC) with conservative surgery and radiation therapy, to compare clinical-pathologic features and long-term outcomes. Methods and Materials: A review of our institution's tumor registry from 1975 to 2007, followed by a central pathology review of available slides, yielded 71 cases of Stage I/II TC and 2,238 cases of Stage I/II IDC treated with breast conservation therapy. Clinical-pathologic features and outcomes were analyzed by subtype to detect significant differences. Results: The median follow-up was 7 years. The TC cohort presented more frequently with pT1 disease (97% vs. 80%, p = 0.0007), pN0 disease (95% vs. 74%, p = 0.0004), hormone-receptor positivity (ER+, 89% vs. 62%, p = 0.0001; PR+, 81% vs. 52%, p = 0.0001), and HER-2 negativity (89% vs. 71%, p = 0.04). Clinical outcomes also favored the TC cohort, with lower rates of breast cancer-related death (1% vs. 10%; p = 0.0109) and distant metastasis (1% vs. 13%; p = 0.0028) and higher rates of 10-year overall (90% vs. 80%; p = 0.033), cause-specific (99% vs. 86%; p = 0.011), and disease-free (99% vs. 82%; p = 0.003) survival. There was a nonsignificant trend toward improved breast cancer relapse-free survival for the TC cohort (95% vs. 87%; p = 0.062) but no difference in nodal relapse-free survival or contralateral breast cancer relapse-free survival (all p values >0.05) between the cohorts. Conclusion: Our institutional experience suggests that TC, when compared with IDC, is associated with more favorable clinical-pathologic features and comparable, if not superior, outcomes after breast conservation therapy, suggesting the appropriateness of a conservative approach to this rare subtype.

  1. [Association of pulmonary carcinoma and ductal breast cancer].

    PubMed

    El Khattabi, W; Lakhdar, N; Jabri, H; Afif, H

    2016-08-01

    Multiple primary cancers are relatively rare. The association between lung and breast cancer is exceptional and requires genetic research and predisposing factors. We report the case of a female patient of 43years, hospitalized for atelectasis of the left lung with breast lumps. Bronchial biopsies have concluded a primary lung adenocarcinoma. Breast biopsy objectified ductal invasive breast cancer. The treatment was a palliative chemotherapy. The evolution is marked by the early death of the patient. Although the association of multiple cancers is rare, their discovery requires a particular treatment regimen depends on the staging of each cancer. PMID:27349825

  2. Activation of antitumor cytotoxic T lymphocytes by fusions of human dendritic cells and breast carcinoma cells

    PubMed Central

    Gong, Jianlin; Avigan, David; Chen, Dongshu; Wu, Zekui; Koido, Shigeo; Kashiwaba, Masahiro; Kufe, Donald

    2000-01-01

    We have reported that fusions of murine dendritic cells (DCs) and murine carcinoma cells reverse unresponsiveness to tumor-associated antigens and induce the rejection of established metastases. In the present study, fusions were generated with primary human breast carcinoma cells and autologous DCs. Fusion cells coexpressed tumor-associated antigens and DC-derived costimulatory molecules. The fusion cells also retained the functional potency of DCs and stimulated autologous T cell proliferation. Significantly, the results show that autologous T cells are primed by the fusion cells to induce MHC class I-dependent lysis of autologous breast tumor cells. These findings demonstrate that fusions of human breast cancer cells and DCs activate T cell responses against autologous tumors. PMID:10688917

  3. A rare case of concurrent signet-ring carcinoma of breast and microangiopathic hemolytic anemia.

    PubMed

    Lara, Kelly; Bae, Esther; Park, Hanna; Hussain, Farabi

    2016-01-01

    Microangiopathic hemolytic anemia (MAHA) can be an uncommon presentation of an underlying malignancy, most often due to signet-ring cell carcinoma (SRCC). Additionally, pure SRCC in a breast primary-tumor comprises <2% of all breast cancers (Shin SY, Park H, Chae SW, Woo HY. Microangiopathic hemolytic anemia as the first manifestation of metastatic signet-ring cell carcinoma of unknown origin: a case report and review of literature. Kor J Lab Med 2011;31:157-61). To the best of our knowledge, the combination of these two entities, pure breast primary SRCC along with MAHA, has not been reported. Here, we present such a rare case. We also evaluate the current literature regarding this and similar disease processes, of which evidence is scarce and further research is needed. PMID:27587305

  4. A rare case of concurrent signet-ring carcinoma of breast and microangiopathic hemolytic anemia†

    PubMed Central

    Lara, Kelly; Bae, Esther; Park, Hanna; Hussain, Farabi

    2016-01-01

    Microangiopathic hemolytic anemia (MAHA) can be an uncommon presentation of an underlying malignancy, most often due to signet-ring cell carcinoma (SRCC). Additionally, pure SRCC in a breast primary-tumor comprises <2% of all breast cancers (Shin SY, Park H, Chae SW, Woo HY. Microangiopathic hemolytic anemia as the first manifestation of metastatic signet-ring cell carcinoma of unknown origin: a case report and review of literature. Kor J Lab Med 2011;31:157–61). To the best of our knowledge, the combination of these two entities, pure breast primary SRCC along with MAHA, has not been reported. Here, we present such a rare case. We also evaluate the current literature regarding this and similar disease processes, of which evidence is scarce and further research is needed. PMID:27587305

  5. A gene expression signature associated with metastatic cells in effusions of breast carcinoma patients.

    PubMed

    Dupont, Virginie N; Gentien, David; Oberkampf, Marine; De Rycke, Yann; Blin, Nathalie

    2007-09-01

    Malignant effusion in invasive breast carcinoma is associated with poor prognosis. To decipher molecular events leading to metastasis and to identify reliable markers for targeted therapies are of crucial need. Therefore, we have used cDNA microarrays to delineate molecular signatures associated with metastasis and relapse in breast carcinoma effusions. Taking advantage of an immunomagnetic method, we have purified to homogeneity EpCAM-positive cells from 34 malignant effusions. Immunopurified cells represented as much as 10% of the whole cell fraction and their epithelial and carcinoma features were confirmed by immunofluorescence labeling. Gene expression profiles of 19 immunopurified effusion samples, were analyzed using human pan-genomic microarrays, and compared with those of 4 corresponding primary tumors, 8 breast carcinoma effusion-derived cell lines, and 4 healthy mammary tissues. Principal component and multiple clustering analyses of microarray data, clearly identified distinctive molecular portraits corresponding to the 4 categories of specimens. Of uppermost interest, effusion samples were arranged in 2 subsets on the basis of their gene expression patterns. The first subset partly shares a gene expression signature with the different cell lines, and overexpresses CD24, CD44 and epithelial cytokeratins 8,18,19. The second subset overexpresses markers related to aggressive invasive carcinoma (uPA receptor, S100A4, vimentin, CXCR4). These findings demonstrate the importance of using pure cell fractions to accurately decipher in silico gene expression of clinical specimens. Further studies will lead to the identification of genes of oustanding importance to diagnose malignant effusion, predict survival and tailor appropriate therapies to the metastatic effusion disease in breast carcinoma patients. PMID:17450528

  6. DNA methyltransferase inhibition increases efficacy of adoptive cellular immunotherapy of murine breast cancer.

    PubMed

    Terracina, Krista P; Graham, Laura J; Payne, Kyle K; Manjili, Masoud H; Baek, Annabel; Damle, Sheela R; Bear, Harry D

    2016-09-01

    Adoptive T cell immunotherapy is a promising approach to cancer treatment that currently has limited clinical applications. DNA methyltransferase inhibitors (DNAMTi) have known potential to affect the immune system through multiple mechanisms that could enhance the cytotoxic T cell responses, including: upregulation of tumor antigen expression, increased MHC class I expression, and blunting of myeloid derived suppressor cells (MDSCs) expansion. In this study, we have investigated the effect of combining the DNAMTi, decitabine, with adoptive T cell immunotherapy in the murine 4T1 mammary carcinoma model. We found that expression of neu, MHC class I molecules, and several murine cancer testis antigens (CTA) was increased by decitabine treatment of 4T1 cells in vitro. Decitabine also increased expression of multiple CTA in two human breast cancer cell lines. Decitabine-treated 4T1 cells stimulated greater IFN-gamma release from tumor-sensitized lymphocytes, implying increased immunogenicity. Expansion of CD11b + Gr1 + MDSC in 4T1 tumor-bearing mice was significantly diminished by decitabine treatment. Decitabine treatment improved the efficacy of adoptive T cell immunotherapy in mice with established 4T1 tumors, with greater inhibition of tumor growth and an increased cure rate. Decitabine may have a role in combination with existing and emerging immunotherapies for breast cancer. PMID:27416831

  7. The fibromatosis signature defines a robust stromal response in breast carcinoma

    PubMed Central

    Beck, Andrew H; Espinosa, Inigo; Gilks, C Blake; van de Rijn, Matt; West, Robert B

    2016-01-01

    Breast cancer is a heterogeneous disease, and the influence of stromal gene and protein expression patterns on the biological and clinical heterogeneity of the disease is poorly understood. We previously demonstrated that evaluation of the gene expression patterns of two soft-tissue tumors (desmoid-type fibromatosis (DTF) and solitary fibrous tumor) could be used to identify distinct stromal reaction patterns in breast carcinoma. In the current study, we examined four additional data sets obtained from four different institutions and containing gene expression data from a total of 561 breast cancer patients. We identified a core set of 66 DTF-associated genes that were consistently coordinately expressed in a subset of 25–35% of breast cancers. Breast carcinomas defined by high levels of coordinated expression of DTF core genes tend to be lower grade, express estrogen receptor, and show significantly longer survival across the four data sets. Using multiple tissue microarrays of archival breast cancer specimens obtained from a total of 745 patients, we demonstrated that a subset of breast cancers show coordinate expression of DTF core proteins by stromal cells in the tumor microenvironment. We evaluated the protein expression of a single DTF core protein (SPARC) on a tissue microarray with clinical outcome data and demonstrated that breast cancers with strong stromal protein expression of SPARC show a trend for increased survival. Our data demonstrate that the DTF core gene set is a robust descriptor of a distinct stromal response that is associated with improved clinical outcome in breast cancer patients. PMID:18414401

  8. Epidemiology, stage at diagnosis, and tumor biology of breast carcinoma in multiracial and multiethnic populations.

    PubMed

    Hunter, C P

    2000-03-01

    All women, regardless of their racial or ethnic origin or heritage, are at risk of developing breast cancer. Variations in breast carcinoma incidence rates among multicultural populations suggest that etiologic factors differ in their biologic expression and impact on disease outcome. Key among those factors that affect breast carcinoma development are the roles of genetics and the environment, the reproductive experience and the effects of endogenous and exogenous hormones in women, the change in immune status and host vulnerability, and the biologic determinants of breast carcinoma. Cultural dynamics, sociodemographic differences, and behavioral characteristics across population subgroups modulate how biologic disease is expressed among different races and ethnic groups. These interactions contribute to the observed variations in breast carcinoma incidence, mortality, and survival. Stage, a measure of disease status, is used to assess prognosis, plan treatment, and evaluate outcome. Numerous studies have reported a more advanced stage of breast carcinoma at diagnosis in racial/ethnic subgroups, especially among women from African American, Hispanic, American Indian, and native Hawaiian cultures. Factors associated with advanced stage at diagnosis in multicultural populations range from changes in the basic biological characteristics at the molecular and cellular level, to more complex behavioral attributes unique to a particular multicultural population, to societal issues-such as access to care and socioeconomic conditions-all of which impact on the health measure called "stage at diagnosis." Rapid advancements in knowledge of cancer biology and of genetic markers and tumor products are providing new mechanisms for identifying etiologic pathways that can be utilized for better screening, detection, treatment and monitoring of disease. Further studies are needed that evaluate the biologic and molecular alterations in tumor development, progression, and response

  9. [Glycogen-rich clear-cell breast carcinoma with neuroendocrine differentiation features].

    PubMed

    Di Tommaso, L; Pasquinelli, G; Portincasa, G; Santini, D

    2001-12-01

    Glycogen-rich, clear cell carcinoma of the breast (GCC) is a rare type of breast cancer. Histological features are usually those of ductal carcinoma, but cases featuring lobular, tubular, and mixed ductal-tubular carcinoma have been reported. The presence of "numerous cells with clear cytoplasm" has been reported in some cases of primary neuro-endocrine tumors of the breast. Moreover, no case of GCC of the breast with neuro-endocrine features has been described. We report a case of 33-year-old woman with a palpable lump of the right breast. Fresh tissue obtained from the operating theatre was fixed in 10% formalin and routinely processed to paraffin. Serial sections were stained with haematoxylin and eosin (H&E), periodic acid Schiff (PAS) and PAS following diastase digestion (PASd); other sections were processed for immunohistological detection of chromogranin, synaptophysin, vimentin and smooth muscle actin. For electron microscopy, the tissue was fixed in 2.5% glutaraldehyde in cacodylate buffer. The samples were post-fixed in osmium, dehydrated in ethanol and embedded in araldite. Thin sections, counterstained in uranyl acetate and lead citrate, were studied under a Philips 400T electron microscope. The lump at histological examination was entirely composed of optically clear, neoplastic cells. The cytoplasm was filled with numerous PAS-positive granules which did not stain after the diastase digestion, leading to a diagnosis of GCC of the breast. Some histological (i.e. pattern of growth, blunt edges of neoplastic glands and numerous vessels) and cytological features (i.e. nuclear monomorphism and fine chromatin) prompted us to investigate the possible neuro-endocrine differentiation of the lesion. Immunohistochemical and ultrastructural studies strongly support such hypothesis. To the best of our knowledge, we report the first case of GCC of the breast with neuro-endocrine features. PMID:11785121

  10. Hypofractionated Image Guided Radiation Therapy in Treating Patients With Stage IV Breast Cancer

    ClinicalTrials.gov

    2016-06-24

    Central Nervous System Metastases; Invasive Ductal Breast Carcinoma; Invasive Ductal Breast Carcinoma With Predominant Intraductal Component; Invasive Lobular Breast Carcinoma; Invasive Lobular Breast Carcinoma With Predominant in Situ Component; Liver Metastases; Lobular Breast Carcinoma in Situ; Lung Metastases; Male Breast Cancer; Medullary Ductal Breast Carcinoma With Lymphocytic Infiltrate; Mucinous Ductal Breast Carcinoma; Papillary Ductal Breast Carcinoma; Recurrent Breast Cancer; Stage IV Breast Cancer; Tubular Ductal Breast Carcinoma; Tumors Metastatic to Brain

  11. Issues Affecting the Loco-regional and Systemic Management of Patients with Invasive Lobular Carcinoma of the Breast.

    PubMed

    Jacobs, Carmel; Clemons, Mark; Addison, Christina; Robertson, Susan; Arnaout, Angel

    2016-01-01

    Invasive lobular carcinoma (ILC) of the breast is the second most common type of invasive breast carcinoma accounting for 8-14% of all breast cancers. Traditional management of ILC has followed similar paradigms as that for invasive ductal carcinoma (IDC). However, ILC represents a pathologically, clinically and biologically unique variant of breast cancer with particular management challenges. These challenges are seen in both the loco-regional management of ILC; where ILC tumors tend to avoid detection and hence present as more clinically advanced and surgically challenging carcinomas, and the systemic management with a unique response pattern to standard systemic therapies. Because of these challenges, the outcome for patients with ILC has likely lagged behind the continued improvements seen in outcome for patients with IDC. Here, we discuss some of the unique challenges ILC presents and discuss possible management strategies to best overcome the difficulties in the loco-regional and systemic management of patients with ILC. PMID:26782951

  12. Metastases to breast simulating ductal carcinoma in situ: report of two cases and review of the literature.

    PubMed

    Gupta, D; Merino, M I; Farhood, A; Middleton, L P

    2001-02-01

    The breast is an uncommon site for metastases. Nevertheless, it is important to differentiate primary from secondary tumors of the breast, because clinical management and expected outcomes are vastly different. We report two examples of tumors with a papillary histologic pattern metastasizing to the breast. One of the cases occurred in a 31-year-old woman with a primary renal cell carcinoma, the other was in a 42-year-old woman with an ovarian papillary serous adenocarcinoma. In the first case, the patient's previous history of cancer was not known to the pathologist. The cases highlight the difficulty in distinguishing primary from metastatic tumors in the breast. In both cases the tumors infiltrated in a pattern that mimicked in situ ductal carcinoma changes. Additionally, in both cases, the metastasizing tumor was unusual with the tumor cells diffusely permeating the lymphatic spaces, not in a solid mass. These cases and a review of the literature indicated that breast metastases, although rare, must be recognized and differentiated from primary breast tumors to avoid unnecessary radical surgery to the breast. Moreover, the presence of changes similar to in situ carcinoma of the breast are not conclusive evidence that one is evaluating a primary breast carcinoma. When there is any unusual histomorphology, a good degree of suspicion is necessary. Ann Diagn Pathol 5:15-20, 2001. PMID:11172202

  13. [Results of conservative therapy in early breast carcinoma].

    PubMed

    Gatĕk, J; Duben, J; Dudesek, B; Schön, J

    2000-05-01

    The authors present a review on the development of views on breast cancer from the beginning of the century and contemporary views on the problem, its solution world-wide and in the Czech Republic. They base on their own group of 475 patients of 1991-1998, they analyze the development of possible solutions of early breast cancer and their view on the discussed problem. With regard to favourable results they advocate progressive breast preserving operations associated with postoperative radiotherapy and the use of the method of sentinel nodes. PMID:10916438

  14. Primary acinic cell carcinoma of the breast: a clinicopathological and immunohistochemical study.

    PubMed

    Shingu, Kiyoshi; Ito, Tokiko; Kaneko, Gengo; Itoh, Nobuo

    2013-01-01

    Acinic cell carcinoma of the breast is an extremely rare, malignant neoplasm characterized by widespread acinar cell-like differentiation and clinically low-grade malignancy. Herein, we report a case of acinic cell carcinoma of the breast in a 41-year-old woman. The tumor was poorly demarcated but had a firm consistency. It was removed with lumpectomy, and sentinel lymph node biopsy was performed to check for metastasis. Microscopically, the tumor showed an infiltrative growth pattern with a combination of solid, trabecular, and microglandular areas. Many of the tumor cells had abundant clear vacuolated cytoplasm containing zymogen-typed granules which resemble acinar cells of the salivary glands. The immunohistochemical profile of the tumor was also similar to that of salivary gland acinic cell carcinoma: the tumor cells were positive for amylase, lysozyme, α -1-antichymotrypsin, S-100 protein, and epithelial membrane antigen and negative for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2. She received postoperative chemoradiation therapy and has been well for 3 years since surgery. As studies on large series are lacking, further studies are needed to elucidate the biological characteristics of acinic cell carcinoma of the breast. PMID:24191209

  15. Putative markers for the detection of breast carcinoma cells in blood.

    PubMed Central

    Eltahir, E. M.; Mallinson, D. S.; Birnie, G. D.; Hagan, C.; George, W. D.; Purushotham, A. D.

    1998-01-01

    The aim of this study was to investigate certain genes for their suitability as molecular markers for detection of breast carcinoma cells using the reverse transcriptase-polymerase chain reaction (RT-PCR). RNA was prepared from MCF-7 breast carcinoma cells and peripheral blood leucocytes of healthy female volunteers. This RNA was screened for mRNA of MUC1, cytokeratin 19 (CK19) and CD44 (exons 8-11) by RT-PCR and the results validated by Southern blots. Variable degrees of expression of MUC1 and CD44 (exons 8-11) were detected in normal peripheral blood, rendering these genes non-specific for epithelial cells and therefore unsuitable for use as markers to detect breast carcinoma cells. Although CK19 mRNA was apparently specific, it was deemed unsuitable for use as a marker of breast cancer cells in light of its limited sensitivity. Furthermore, an attempt at using nested primers to increase sensitivity resulted in CK19 mRNA being detected after two amplification rounds in blood from healthy volunteers. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:9579823

  16. Phospholipid hydroperoxide glutathione peroxidase (PHGPx) expression is downregulated in poorly differentiated breast invasive ductal carcinoma.

    PubMed

    Cejas, P; García-Cabezas, M A; Casado, E; Belda-Iniesta, C; De Castro, J; Fresno, J A; Sereno, M; Barriuso, J; Espinosa, E; Zamora, P; Feliu, J; Redondo, A; Hardisson, D A; Renart, J; González-Barón, M

    2007-06-01

    Phospholipid Hydroperoxide Glutathione Peroxidase (PHGPx) is the only known enzyme able to reduce lipid peroxides bound to cell membranes. Moreover it has been involved in apoptosis and can influence intracellular signaling. To investigate the possible relationship between PHGPx and human cancer we have quantified PHGPx expression levels by real-time quantitative PCR and immunohistochemistry in tissue samples of human breast invasive ductal carcinoma from 34 patients compared with their own controls of benign breast tissue. PHGPx expression levels were compared with the clinical and pathological data of these patients. The results showed that PHGPx expression levels are downregulated in poorly differentiated (grade 3) breast invasive ductal carcinoma (P = 0.0043). PHGPx expression levels decreased gradually with tumor grade from grade 1 to grade 3. We also found a downregulation of PHGPx in cases that showed p53 accumulation compared with cases without p53 immunostaining (P = 0.0011). PHGPx was also downregulated in cases without progesterone receptors (PR) immunostaining compared with cases with PR immunostaining (P = 0.0165). Grade 3, p53 immunostaining and absence of PR immunostaining are poor prognostic factors. These results suggest that PHGPx downregulation could be related with a poorer prognosis in breast invasive ductal carcinoma. PMID:17516241

  17. Geographic distribution of co-dominant DNA stemlines in breast carcinoma

    SciTech Connect

    Visscher, D.; Dolan, P.; Ottosen, S.; Crissman, J.

    1995-09-01

    Breast carcinomas often contain multiple DNA stemlines in flow cytometric DNA histograms. However, due to mixing during tissue disaggregation the microanatomical relationship between the cells which comprise distinct stemlines is unclear. We performed image cytophotometric DNA analysis (IA) on two separate areas of intact tissue sections of 19 breast carcinomas which were selected on the basis of flow cytometric (FCM) DNA content heterogeneity (i.e., multiple stemlines). For comparison, similar analyses were performed on seven tumors with unimodal FCM DNA histograms. Six of the 7 tumors (86%) with unimodal FCM histograms were also unimodal in both IA DNA histograms. Among tumors with heterogeneous FCM DNA histograms, the presence of multiple stemlines was confirmed in IA DNA histograms in 16/19. In nine of these 16 cases, multiple DNA stemlines having similar DNA indices were present in both areas of neoplasm examined with IA. The remaining seven cases displayed unimodal IA histograms in both areas, however DNA indices differed between the two histograms. These findings imply that cell populations corresponding to flow cytometrically detected DNA stemlines are often intimately admixed, even within geographically separated portions of breast tumors. This pattern suggests that productive interactions between genetically distinct tumor populations may lead to stable co-dominance of ancestral clones during progression of some breast carcinomas. 12 refs., 4 tabs.

  18. Progesterone receptors in routinely paraffin-embedded primary breast carcinomas and lymph node metastases.

    PubMed

    Müller-Holzner, E; Zeimet, A G; Daxenbichler, G; Marth, C; Müller, L C; Dapunt, O

    1993-01-01

    Described here is an immunohistochemical technique using the commercially available monoclonal progesterone receptor (PR) antibody KD 68 in routinely fixed and paraffin-embedded breast carcinomas and lymph node metastases. The authors' technique is compared with several incubation variations. The method applying the primary antibody in a dilution of 1:10 overnight followed by a biotinylated second antibody showed the best results when Triton X-100 was added to the buffer. Using this method, comparison with the results on frozen sections of 34 breast carcinomas yielded a significant concordance of 94%. Correlation between the results on paraffin sections and those obtained by the standard dextran-coated charcoal cytosol assay was 80%. The value of the method for predicting endocrine therapy response was shown in 20 patients. Thus the reliability of the method has been demonstrated and was applied on 151 lymph node metastases and the corresponding primary breast carcinomas from 50 patients. Generally PR content in the metastases was lower than in the primary tumors (p < 0.001). This finding indicates that evaluation of PR in lymph node metastases should be included in the decision for endocrine therapy of breast cancer. PMID:7686056

  19. Blockade of MMP14 Activity in Murine Breast Carcinomas: Implications for Macrophages, Vessels, and Radiotherapy

    PubMed Central

    Ager, Eleanor I.; Kozin, Sergey V.; Kirkpatrick, Nathaniel D.; Seano, Giorgio; Kodack, David P.; Askoxylakis, Vasileios; Huang, Yuhui; Goel, Shom; Snuderl, Matija; Muzikansky, Alona; Finkelstein, Dianne M.; Dransfield, Daniel T.; Devy, Laetitia; Boucher, Yves

    2015-01-01

    Background: Matrix metalloproteinase (MMP) 14 may mediate tumor progression through vascular and immune-modulatory effects. Methods: Orthotopic murine breast tumors (4T1 and E0771 with high and low MMP14 expression, respectively; n = 5–10 per group) were treated with an anti-MMP14 inhibitory antibody (DX-2400), IgG control, fractionated radiation therapy, or their combination. We assessed primary tumor growth, transforming growth factor β (TGFβ) and inducible nitric oxide synthase (iNOS) expression, macrophage phenotype, and vascular parameters. A linear mixed model with repeated observations, with Mann-Whitney or analysis of variance with Bonferroni post hoc adjustment, was used to determine statistical significance. All statistical tests were two-sided. Results: DX-2400 inhibited tumor growth compared with IgG control treatment, increased macrophage numbers, and shifted the macrophage phenotype towards antitumor M1-like. These effects were associated with a reduction in active TGFβ and SMAD2/3 signaling. DX-2400 also transiently increased iNOS expression and tumor perfusion, reduced tissue hypoxia (median % area: control, 20.2%, interquartile range (IQR) = 6.4%-38.9%; DX-2400: 1.2%, IQR = 0.2%-3.2%, P = .044), and synergistically enhanced radiation therapy (days to grow to 800mm3: control, 12 days, IQR = 9–13 days; DX-2400 plus radiation, 29 days, IQR = 26–30 days, P < .001) in the 4T1 model. The selective iNOS inhibitor, 1400W, abolished the effects of DX-2400 on vessel perfusion and radiotherapy. On the other hand, DX-2400 was not capable of inducing iNOS expression or synergizing with radiation in E0771 tumors. Conclusion: MMP14 blockade decreased immunosuppressive TGFβ, polarized macrophages to an antitumor phenotype, increased iNOS, and improved tumor perfusion, resulting in reduced primary tumor growth and enhanced response to radiation therapy, especially in high MMP14-expressing tumors. PMID:25710962

  20. Assessment of Pathological Response of Breast Carcinoma in Modified Radical Mastectomy Specimens after Neoadjuvant Chemotherapy.

    PubMed

    Vasudevan, Dhanya; Jayalakshmy, P S; Kumar, Suresh; Mathew, Siji

    2015-01-01

    Aim. Paclitaxel based neoadjuvant chemotherapy regimen (NAT) in the setting of locally advanced breast cancer (LABC) can render inoperable tumor (T4, N2/N3) resectable. The aim of this study was to assess the status of carcinoma in the breast and lymph nodes after paclitaxel based NAT in order to find out the patient and the tumor characteristics that correspond to the pathological responses which could be used as a surrogate biomarker to assess the treatment response. Materials and Methods. Clinical and tumor characteristics of patients with breast carcinoma (n = 48) were assessed preoperatively. These patients were subjected to modified radical mastectomy after 3 courses of paclitaxel based NAT regimen. The pathological responses of the tumor in the breast and the lymph nodes were studied by using Chevallier's system which graded the responses into pathological complete response (pCR), pathological partial response (pPR), and pathological no response (pNR). Results. Our studies showed a pCR of 27.1% and a pPR of 70.9% . Clinically small sized tumors (2-5 cms) and Bloom Richardson's grade 1 tumors showed a pCR. Mean age at presentation was 50.58 yrs. 79.2% of cases were invasive ductal carcinoma NOS; only 2.1% were invasive lobular carcinoma, their response to NAT being the same. There was no downgrading of the tumor grades after NAT. Ductal carcinoma in situ and lymphovascular invasion were found to be resistant to chemotherapy. The histopathological changes noted in the lymph nodes were similar to that found in the tumor bed. Discussion and Conclusion. From our study we conclude that histopathological examination of the tumor bed is the gold standard for assessing the chemotherapeutic tumor response. As previous studies have shown pCR can be used as a surrogate biomarker to assess the tumor response. PMID:26697228

  1. Proliferative activity is a significant prognostic factor in male breast carcinoma.

    PubMed Central

    Pich, A.; Margaria, E.; Chiusa, L.

    1994-01-01

    The proliferative activity of male breast carcinoma has been investigated using the staining of the argyrophilic nucleolar organizer regions (AgNORs), the monoclonal antibody against the proliferating cell nuclear antigen (PC10) and the monoclonal antibody MIB-1 in formalin-fixed, paraffin-embedded specimens from 27 primary male breast carcinomas at diagnosis. A significant correlation was found between survival and AgNOR counts (median of survival 77 months for cases with AgNOR/cell < or = 7.27 but 37 months only for cases with > 7.27 AgNOR/cell; P = 0.001), proliferating cell nuclear antigen scores (median of survival 73 months for cases with proliferating cell nuclear antigen < or = 18.25% versus 41 for cases with proliferating cell nuclear antigen > 18.25%; P = 0.013) and MIB-1 scores (median of survival 73 months for cases with MIB-1 scores < or = 23.5% versus 37 months for cases with MIB-1 scores > 23.5%; P = 0.01). Tumor histological grade was also correlated with prognosis (median of survival 72 months for grade 2 versus 33 months for grade 3 tumors; P = 0.01). Estrogen and progesterone receptors, immunohistochemically detected on paraffin-embedded sections, had no prognostic value. In the multivariate survival analysis, only AgNOR counts (P = 0.007) and tumor size (P = 0.003) had an independent prognostic significance. Our results indicate that methods for assessing the cell proliferation in routinely processed specimens offer significant prognostic information in male breast carcinoma. The finding, together with the lack of prognostic significance for estrogen receptors and progesterone receptors, suggests that male breast carcinoma is biologically different from female breast cancer. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:7519830

  2. Novel applications of proton therapy in breast carcinoma.

    PubMed

    Cuaron1, John J; MacDonald, Shannon M; Cahlon, Oren

    2016-08-01

    This review will focus on the indications, clinical experience, and technical considerations of proton beam radiation therapy in the treatment of patients with breast cancer. For patients with early stage disease, proton therapy delivers less dose to non-target breast tissue for patients receiving partial breast irradiation (PBI) therapy, which may result in improved cosmesis but requires further investigation. For patients with locally advanced breast cancer requiring treatment to the regional lymph nodes, proton therapy allows for an improved dosimetric profile compared with conventional photon and electron techniques. Early clinical results demonstrate acceptable toxicity. The possible reduction in cardiopulmonary events as a result of reduced dose to organs at risk will be tested in a randomized control trial of protons vs. photons. PMID:27558253

  3. Bone scanning in pregnant patients with breast carcinoma

    SciTech Connect

    Baker, J.; Ali, A.; Groch, M.W.; Fordham, E.; Economou, S.G.

    1987-07-01

    Radionuclide scanning is usually contraindicated in pregnancy because of the danger of fetal radiation exposure. Radionuclide bone scanning with Tc-99m MDP is a sensitive indicator of early osseous metastases in breast cancer. Three cases of breast cancer during pregnancy are reported; modified bone scanning was utilized for staging and decision analysis. Modifications of bone scanning techniques to minimize fetal radiation exposure and fetal dosimetry calculations are described.

  4. Clinicopathologic features and long-term outcome of patients with medullary breast carcinoma managed with breast-conserving therapy (BCT)

    SciTech Connect

    Ha Vu-Nishino; Tavassoli, Fattaneh A.; Ahrens, Willam A.; Haffty, Bruce G. . E-mail: hafftybg@umdnj.edu

    2005-07-15

    Purpose: The purpose of this study is to compare the clinical characteristics and outcome of medullary carcinoma to infiltrating ductal carcinoma of the breast in a large cohort of conservatively managed patients with long-term follow-up. Methods and Materials: Chart records of patients with invasive breast cancer managed with breast-conserving therapy (BCT) at the therapeutic radiology facilities of Yale University School of Medicine before 2001 were reviewed. Forty-six cases (1971-2001) were identified with medullary histology; 1,444 patients with infiltrating ductal carcinoma served as a control group. Results: The medullary cohort presented at a younger age with a higher percentage of patients in the 35 years or younger age group (26.1% vs. 6.6%, p < 0.00001). Twelve patients with medullary histology underwent genetic screening, and 6 patients were identified with deleterious mutations. This group showed greater association with BRCA1/2 mutations compared with screened patients in the control group (50.0% vs. 15.8%, p 0.0035). The medullary cohort was also significantly associated with greater T stage and tumor size (37.0% vs. 17.2% T2, mean size 3.2 vs. 2.5 cm, p 0.00097) as well as negative ER (84.9% vs. 37.6%, p < 0.00001) and PR (87.5% vs. 48.1%, p = 0.00001) status. As of February 2003, median follow-up times for the medullary and control groups were 13.9 and 14.0 years, respectively. Although breast relapse-free rates were not significantly different (76.7% vs. 85.2%), 10-year distant relapse-free survival in the medullary cohort was significantly better than in the control group (94.9% vs. 77.5%, p = 0.028). Conclusions: Despite poor clinicopathologic features, patients with medullary histology demonstrate favorable long-term distant relapse-free survival. Local control rates of patients with medullary and infiltrating ductal carcinoma are comparable. These findings suggest that patients diagnosed with medullary carcinoma are appropriate candidates for

  5. Extremely rare presentation of soft tissue metastasis from carcinoma breast as a massive swelling of upper extremity.

    PubMed

    Purkayastha, Abhishek; Sharma, Neelam

    2016-04-01

    Soft tissue metastasis from any primary malignancy is considered very rare and a breast carcinoma metastasizing to soft tissue is still rarer. To the best of our knowledge, carcinoma breast with soft tissue metastasis to upper extremity is very uncommon with only six cases been reported in world literature till date and our case is the seventh such case in an 80-year-old female, previously treated for carcinoma right breast 15 years ago. The patient presented with progressive painful massive swelling of right upper arm measuring 21 cm × 17 cm, of 2 months duration. Histopathological examination of the swelling showed metastatic deposits from a poorly differentiated adenocarcinoma. Further immunohistochemical (IHC) analysis revealed tumor cells staining positive for estrogen and progesterone receptors while negative for HER 2-Nu, desmin, epithelial membrane antigen, CK7 and thyroid transcription factor-1 (TTF-1), suggestive of metastasis from a primary breast carcinoma. Only few case series and isolated cases reports have been published regarding any primary malignancy or breast carcinoma metastasizing to soft tissues. A thorough review of literature also reveals that our case is the largest soft tissue metastatic swelling from breast carcinoma ever reported. We hereby present this case with review of literature to highlight its extreme rarity, unusual presentation, clinicopathological characteristics and its overall prognosis. PMID:27121743

  6. Presence of papillomavirus sequences in condylomatous lesions of the mamillae and in invasive carcinoma of the breast

    PubMed Central

    de Villiers, Ethel-Michele; Sandstrom, Robert E; zur Hausen, Harald; Buck, Charles E

    2005-01-01

    Background Viruses including Epstein–Barr virus (EBV), a human equivalent of murine mammary tumour virus (MMTV) and human papillomavirus (HPV) have been implicated in the aetiology of human breast cancer. We report the presence of HPV DNA sequences in areolar tissue and tumour tissue samples from female patients with breast carcinoma. The presence of virus in the areolar–nipple complex suggests to us a potential pathogenic mechanism. Methods Polymerase chain reaction (PCR) was undertaken to amplify HPV types in areolar and tumour tissue from breast cancer cases. In situ hybridisation supported the PCR findings and localised the virus in nipple, areolar and tumour tissue. Results Papillomavirus DNA was present in 25 of 29 samples of breast carcinoma and in 20 of 29 samples from the corresponding mamilla. The most prevalent type in both carcinomas and nipples was HPV 11, followed by HPV 6. Other types detected were HPV 16, 23, 27 and 57 (nipples and carcinomas), HPV 20, 21, 32, 37, 38, 66 and GA3-1 (nipples only) and HPV 3, 15, 24, 87 and DL473 (carcinomas only). Multiple types were demonstrated in seven carcinomas and ten nipple samples. Conclusions The data demonstrate the occurrence of HPV in nipple and areolar tissues in patients with breast carcinoma. The authors postulate a retrograde ductular pattern of viral spread that may have pathogenic significance. PMID:15642157

  7. Comparative genomic hybridization analysis of invasive ductal breast carcinomas in the Chinese population

    PubMed Central

    ZHANG, JIANWEI; ZHANG, HONGYAN; XU, XIN; WANG, MINGRONG; YU, ZHONGHE

    2015-01-01

    Breast cancer is the most common malignancy in Chinese women. The aim of the present study was to investigate the genetic alterations that occur in breast cancer cells in Chinese women. Comparative genomic hybridization (CGH) analysis was performed on 34 tumors obtained from patients with primary invasive ductal breast carcinoma (IDC). Recurrent genetic alterations in breast cancer include gains on chromosomes 1q (59%), 16p (50%), 17q (44%), 8q (38%), 11q (32%), 20q (32%), 1p (24%), 20p (24%), 19q (21%) and 19p (18%). Losses are common on chromosomes 6q (15%), 8p (12%), 18 (12%), 4q (9%), X (9%) and 17p (9%). In the present study, high-level amplifications were observed on chromosomes 1q32, 8p, 11q13, 17q and 20q. Overall, the chromosomal DNA gains observed were consistent with the changes reported in Caucasian populations. However, the incidence of chromosomal DNA loss was lower in the present study compared with the incidence reported in the literature. The present results demonstrate the pattern of chromosomal imbalances in the invasive ductal breast carcinomas of Chinese females. PMID:26622803

  8. Differences between invasive lobular and invasive ductal carcinoma of the breast: results and therapeutic implications

    PubMed Central

    Barroso-Sousa, Romualdo; Metzger-Filho, Otto

    2016-01-01

    Invasive lobular carcinoma (ILC) is the second most common histologic subtype of breast cancer (BC): ILC differs from invasive ductal carcinoma (IDC) in its clinicopathological characteristics and responsiveness to systemic therapy. From the clinical standpoint, data suggest that ILC derives a distinct benefit from systemic therapy compared to IDC. In addition, comprehensive molecular analyses have been reported for ILCs, confirming that these tumors have specific genomic profiles compared to IDC. Despite these differences, clinical trials and practical clinical guidelines tend to treat BC as a single entity. Here we discuss these clinical and molecular data and their therapeutic implications. PMID:27482285

  9. Overview of the randomized trials of radiotherapy in ductal carcinoma in situ of the breast.

    PubMed

    Correa, C; McGale, P; Taylor, C; Wang, Y; Clarke, M; Davies, C; Peto, R; Bijker, N; Solin, L; Darby, S

    2010-01-01

    Individual patient data were available for all four of the randomized trials that began before 1995, and that compared adjuvant radiotherapy vs no radiotherapy following breast-conserving surgery for ductal carcinoma in situ (DCIS). A total of 3729 women were eligible for analysis. Radiotherapy reduced the absolute 10-year risk of any ipsilateral breast event (ie, either recurrent DCIS or invasive cancer) by 15.2% (SE 1.6%, 12.9% vs 28.1% 2 P <.00001), and it was effective regardless of the age at diagnosis, extent of breast-conserving surgery, use of tamoxifen, method of DCIS detection, margin status, focality, grade, comedonecrosis, architecture, or tumor size. The proportional reduction in ipsilateral breast events was greater in older than in younger women (2P < .0004 for difference between proportional reductions; 10-year absolute risks: 18.5% vs 29.1% at ages <50 years, 10.8% vs 27.8% at ages ≥ 50 years) but did not differ significantly according to any other available factor. Even for women with negative margins and small low-grade tumors, the absolute reduction in the 10-year risk of ipsilateral breast events was 18.0% (SE 5.5, 12.1% vs 30.1%, 2P = .002). After 10 years of follow-up, there was, however, no significant effect on breast cancer mortality, mortality from causes other than breast cancer, or all-cause mortality. PMID:20956824

  10. Proteomic profiling of 13 paired ductal infiltrating breast carcinomas and non-tumoral adjacent counterparts.

    PubMed

    Pucci-Minafra, Ida; Cancemi, Patrizia; Marabeti, Maria Rita; Albanese, Nadia Ninfa; Di Cara, Gianluca; Taormina, Pietra; Marrazzo, Antonio

    2007-01-01

    According to recent statistics, breast cancer remains one of the leading causes of death among women in Western countries. Breast cancer is a complex and heterogeneous disease, presently classified into several subtypes according to their cellular origin. Among breast cancer histotypes, infiltrating ductal carcinoma represents the most common and potentially aggressive form. Despite the current progress achieved in early cancer detection and treatment, including the new generation of molecular therapies, there is still need for identification of multiparametric biomarkers capable of discriminating between cancer subtypes and predicting cancer progression for personalized therapies. One established step in this direction is the proteomic strategy, expected to provide enough information on breast cancer profiling. To this aim, in the present study we analyzed 13 breast cancer tissues and their matched non-tumoral tissues by 2-DE. Collectively, we identified 51 protein spots, corresponding to 34 differentially expressed proteins, which may represent promising candidate biomarkers for molecular-based diagnosis of breast cancer and for pattern discovery. The relevance of these proteins as factors contributing to breast carcinogenesis is discussed. PMID:21136615

  11. An iTEP-salinomycin nanoparticle that specifically and effectively inhibits metastases of 4T1 orthotopic breast tumors.

    PubMed

    Zhao, Peng; Xia, Guiquan; Dong, Shuyun; Jiang, Zhaong-Xing; Chen, Mingnan

    2016-07-01

    Cancer stem cell (CSC) inhibitors are a new category of investigational drugs to treat metastasis. Salinomycin (Sali) is one of most studied CSC inhibitors and has reached clinical tests. Several drug carriers have been developed to improve efficacy of Sali. However, Sali has not been shown to inhibit metastasis from orthotopic tumors, the gold standard for metastasis. To fill this gap, we developed an immune-tolerant, elastin-like polypeptide (iTEP)-based nanoparticle (iTEP-Sali-ABA NP) that released 4-(aminomethyl)benzaldehyde-modified Sali (Sali-ABA) under acidic conditions. We found that the NP increased the area under the curve (AUC) of Sali-ABA by 30-fold and the tumor accumulation by 3.4-fold. Furthermore, no metastasis was detected in any of the mice given the NP. However, all the mice died of primary tumor burdens. To overcome primary tumor growth and improve the overall survival, we applied a combination therapy consisting of the iTEP-Sali-ABA NP and iTEP NP-delivered paclitaxel. This therapy effectively retarded primary tumor growth, and most importantly, improved the overall survival. In conclusion, delivery of Sali-ABA by the NP, alone or in combination with paclitaxel, was more effective than free Sali-ABA in decreasing metastasis and increasing survival. This iTEP-Sali-ABA NP represents a novel and clinically promising therapy to combat metastasis. PMID:27060212

  12. Axillary lymph node metastases in adenoid cystic carcinoma of the breast. A rare finding

    PubMed Central

    SPILIOPOULOS, D.; MITSOPOULOS, G.; KAPTANIS, S.; HALKIAS, C.

    2015-01-01

    Adenoid cystic carcinoma (ACC) of the breast is a rare malignant salivary-type neoplasm that has a good prognosis and represents less than 1% of all breast cancers. It is a triple negative carcinoma that presents as a painful mass. The mean age at the time of diagnosis is 50–60 years old. The solid variant of this type of tumour with basaloid features and presence of nodal metastases is very rare and considered to have a more aggressive clinical course. We present a case with presence of axillary lymph node metastases that was successfully treated with no evidence of recurrence one year after the diagnosis and review the literature. PMID:26712257

  13. Breast carcinomas fulfill the Warburg hypothesis and provide metabolic markers of cancer prognosis.

    PubMed

    Isidoro, Antonio; Casado, Enrique; Redondo, Andrés; Acebo, Paloma; Espinosa, Enrique; Alonso, Andrés M; Cejas, Paloma; Hardisson, David; Fresno Vara, Juan A; Belda-Iniesta, Cristobal; González-Barón, Manuel; Cuezva, José M

    2005-12-01

    The aim of this study was to investigate selected proteomic markers of the metabolic phenotype of breast carcinomas as prognostic markers of cancer progression. For this purpose, a series of 101 breast carcinomas and 13 uninvolved breast samples were examined for quantitative differences in protein expression of mitochondrial and glycolytic markers. The beta-subunit of the mitochondrial H(+)-ATP synthase (beta-F1-ATPase) and heat shock protein 60 (Hsp60), and the glycolytic glyceraldehyde-3-phosphate dehydrogenase, pyruvate kinase and lactate dehydrogenase were identified by immunological techniques. Correlations of the expression level of the protein markers and of the ratios derived from them were established with the clinicopathological information of the tumors and the follow-up data of the patients. The metabolic proteome of breast cancer specimens revealed a pronounced shift towards an enhanced glycolytic phenotype concurrent with a profound alteration on the mitochondrial beta-F1-ATPase/Hsp60 ratio when compared with normal samples. Discriminant analysis using markers of the metabolic signature as predictor variables revealed a classification sensitivity of approximately 97%. Kaplan-Meier survival analysis showed that several of the proteomic variables significantly correlated with overall and disease-free survival of the patients. The expression level of beta-F1-ATPase per se allowed the identification of a subgroup of breast cancer patients with significantly worse prognosis. Multivariate Cox regression analysis indicated that tumor expression of beta-F1-ATPase is a significant marker independent from clinical variables to assess the prognosis of the patients. We conclude that the alteration of the mitochondrial and glycolytic proteomes is a hallmark feature of breast cancer further providing relevant markers to aid in the prognosis of breast cancer patients. PMID:16033770

  14. [Mucin-like carcinoma-associated antigen: sensitivity and specificity in metastatic breast cancer].

    PubMed

    Ammon, A; Eiffert, H; Alhusen, R; Weber, M; Rümelin, B; Groh, E; Bartsch, H; Marschner, N; Nagel, G A; Krieger, G

    1990-06-01

    The clinical usefulness of a tumor marker essentially depends on its sensitivity and specificity for a certain tumor. To prove, wheather the new tumor marker 'mucin-like carcinoma-associated antigen' could be used for the management of breast cancer patients, we determined its serum concentration in 50 healthy blood donors, 130 patients with various non-malignant diseases, 138 patients with different metastazised tumors and 137 breast cancer patients. 78 of the breast cancer patients had known metastases while 59 had no evidence of disease after initial surgical and adjuvant therapy. Only 2% of the blood donors and 3% of the patients with non-malignant diseases exceeded the cut-off level of 15 U/ml. In contrast to these findings, 28% of patients with various metastazised tumors and 77% of patients with metastazised breast cancer had serum levels above 15 U/ml. Breast cancer patients without evidence of disease had elevated marker values in only 3%. In breast cancer the serum levels of this antigen depends on the type of metastases. Maximal concentrations were found in mixed metastases while cutaneous or lymph-node metastases showed the lowest rate of positivity. Furthermore a good correlation of serial determined marker levels with the course of the disease was observed, so that we conclude, that mucin-like carcinoma-associated antigen can be used in follow-up of patients with metastazised breast cancer. Because of its high sensitivity and specificity it provides some advantage over other markers used in this disease. PMID:2204009

  15. Cellular growth and survival are mediated by beta 1 integrins in normal human breast epithelium but not in breast carcinoma

    SciTech Connect

    Howlett, Anthony R; Bailey, Nina; Damsky, Caroline; Petersen, Ole W; Bissell, Mina J

    1994-11-28

    We previously established a rapid three-dimensional assay for discrimination of normal and malignant human breast epithelial cells using a laminin-rich reconstituted basement membrane. In this assay, normal epithelial cells differentiate into well-organized acinar structures whereas tumor cells fail to recapitulate this process and produce large, disordered colonies. The data suggest that breast acinar morphogenesis and differentiation is regulated by cell-extracellular matrix (ECM) interactions and that these interactions are altered in malignancy. Here, we investigated the role of ECM receptors (integrins) in these processes and report on the expression and function of potential laminin receptors in normal and tumorigenic breast epithelial cells. Immmunocytochemical analysis showed that normal and carcinoma cells in a three-dimensional substratum express profiles of integrins similar to normal and malignant breast tissues in situ. Normal cells express {alpha}1, {alpha}2, {alpha}3, {alpha}6, {beta}1 and {beta}4 integrin subunits, whereas breast carcinoma cells show variable losses, disordered expression, or down regulation of these subunits. Function-blocking experiments using inhibitory antiintegrin subunit antibodies showed a >5-fold inhibition of the formation of acinar structures by normal cells in the presence of either anti-{beta}1 or anti-{alpha}3 antibodies, whereas anti-{alpha}2 or -{alpha}6 had little or no effect. In experiments where collagen type I gels were used instead of basement membrane, acinar morphogenesis was blocked by anti-{beta}1 and -{alpha}2 antibodies but not by anti-{alpha}3. These data suggest a specificity of integrin utilization dependent on the ECM ligands encountered by the cell. The interruption of normal acinar morphogenesis by anti-integrin antibodies was associated with an inhibition of cell growth and induction of apoptosis. Function-blocking antibodies had no inhibitory effect on the rate of tumor cell growth, survival or

  16. Quantitative Ultrasound Comparison of MAT and 4T1 Mammary Tumors in Mice and Rats Across Multiple Imaging Systems

    PubMed Central

    Wirtzfeld, Lauren A.; Ghoshal, Goutam; Rosado-Mendez, Ivan M.; Nam, Kibo; Park, Yeonjoo; Pawlicki, Alexander D.; Miller, Rita J.; Simpson, Douglas G.; Zagzebski, James A.; Oelze, Michael L.; Hall, Timothy J.; O’Brien, William D.

    2015-01-01

    Objectives Quantitative ultrasound estimates such as the frequency-dependent backscatter coefficient (BSC) have the potential to enhance noninvasive tissue characterization and to identify tumors better than traditional B-mode imaging. Thus, investigating system independence of BSC estimates from multiple imaging platforms is important for assessing their capabilities to detect tissue differences. Methods Mouse and rat mammary tumor models, 4T1 and MAT, respectively, were used in a comparative experiment using 3 imaging systems (Siemens, Ultrasonix, and VisualSonics) with 5 different transducers covering a range of ultrasonic frequencies. Results Functional analysis of variance of the MAT and 4T1 BSC-versus-frequency curves revealed statistically significant differences between the two tumor types. Variations also were found among results from different transducers, attributable to frequency range effects. At 3 to 8 MHz, tumor BSC functions using different systems showed no differences between tumor type, but at 10 to 20 MHz, there were differences between 4T1 and MAT tumors. Fitting an average spline model to the combined BSC estimates (3–22 MHz) demonstrated that the BSC differences between tumors increased with increasing frequency, with the greatest separation above 15 MHz. Confining the analysis to larger tumors resulted in better discrimination over a wider bandwidth. Conclusions Confining the comparison to higher ultrasonic frequencies or larger tumor sizes allowed for separation of BSC-versus-frequency curves from 4T1 and MAT tumors. These constraints ensure that a greater fraction of the backscattered signals originated from within the tumor, thus demonstrating that statistically significant tumor differences were detected. PMID:26206823

  17. A Cross-Sectional Study on the Palmar Dermatoglyphics in Relation to Carcinoma Breast Patients

    PubMed Central

    Raizada, Aprajita; Johri, Vishwawas; Ramnath, T; Chowdhary, DS; Garg, RP

    2013-01-01

    Introduction: Dermatoglyphics is a collective term for all the integumentary features (skin patterning of the fingers, toes, palms and soles) and it applies to the division of the anatomy which embraces their study. Aims and Objectives: The purpose of this study was to examine the predominant finger tip patterns in the patients of carcinoma breast. An attempt is also being made to devise a score to assess the risk variables. Materials and Methods: The fingerprints of 100 carcinoma breast patients were obtained and they were compared with those of 100 females who were not suffering from any malignancy till date. The different quantitative parameters of each hand of both the cancer patients and the controls were studied. The parameters which were included were the fingertip ridge pattern, the ridge count in the individual fingers, the Total Finger Ridge Count (TFRC) and the Absolute Finger Ridge Count (AFRC). Results: There was a significant increase in the arch pattern and a decrease in the radial loops in the right thumb (p<0.001), the left thumb (p<0.001), the left index finger (p<0.001) and the left middle finger (p<0.001). A comparison of all the five fingers of both the left and right hands of the cancer patients with the controls showed an arch pattern (p<0.001) with the highest frequency. The lower values of the TFRC (below 50) were associated with carcinoma breast .The lower values of the AFRC (below 100) were associated with the cancer patients. Conclusion: This study was able to establish a specific finger tip predominance in the Carcinoma breast patients. PMID:23730629

  18. Recombinant epoetins do not stimulate tumor growth in erythropoietin receptor-positive breast carcinoma models.

    PubMed

    LaMontagne, Kenneth R; Butler, Jeannene; Marshall, Deborah J; Tullai, Jennifer; Gechtman, Ze'ev; Hall, Chassidy; Meshaw, Alan; Farrell, Francis X

    2006-02-01

    We investigated the significance of erythropoietin receptor (EPOR) expression following treatment with recombinant human erythropoietin (rHuEPO; epoetin alpha) and the effect of recombinant epoetins (epoetin alpha, epoetin beta, and darbepoetin alpha) alone or in combination with anticancer therapy on tumor growth in two well-established preclinical models of breast carcinoma (MDA-MB-231 and MCF-7 cell lines). Expression and localization of EPOR under hypoxic and normoxic conditions in MDA-MB-231 and MCF-7 cells were evaluated by immunoblotting, flow cytometry, and immunohistochemistry. EPOR binding was evaluated using [125I]rHuEPO. Proliferation, migration, and signaling in MDA-MB-231 and MCF-7 cells following treatment with rHuEPO were evaluated. Tumor growth was assessed following administration of recombinant epoetins alone and in combination with paclitaxel (anticancer therapy) in orthotopically implanted MDA-MB-231 and MCF-7 breast carcinoma xenograft models in athymic mice. EPOR expression was detected in both tumor cell lines. EPOR localization was found to be exclusively cytosolic and no specific [125I]rHuEPO binding was observed. There was no stimulated migration, proliferation, or activation of mitogen-activated protein kinase and AKT following rHuEPO treatment. In mice, treatment with recombinant epoetins alone and in combination with paclitaxel resulted in equivalent tumor burdens compared with vehicle-treated controls. Results from our study suggest that although EPOR expression was observed in two well-established breast carcinoma cell lines, it was localized to a cytosolic distribution and did not transduce a signaling cascade in tumors that leads to tumor growth. The addition of recombinant epoetins to paclitaxel did not affect the outcome of paclitaxel therapy in breast carcinoma xenograft models. These results show that recombinant epoetins do not evoke a physiologic response on EPOR-bearing tumor cells as assessed by numerous variables

  19. Quantitative immunohistochemical expression of c Kit in breast carcinomas is predictive of patients' outcome

    PubMed Central

    Charpin, C; Giusiano, S; Charfi, S; Secq, V; Carpentier, S; Andrac, L; Lavaut, M-N; Allasia, C; Bonnier, P; Garcia, S

    2009-01-01

    Background: c Kit (CD117) expression in tissues has been reported as a relevant target for specific therapy in some human malignancies, but has been poorly documented in breast carcinomas Methods: The prognostic significance of c Kit in a series of 924 breast carcinomas (mean follow-up, 79 months) was investigated using standardised high-throughput quantitative densitometry of immunohistochemical precipitates in tissue microarrays. Results: c Kit was expressed in 14.7% breast carcinomas (and in 42 out of 586 node-negative tumours). In univariate analysis, (log-rank test) the score of c Kit expression correlated with poor patient outcome P=0.02 and particularly in node-negative cases (P=0.002). In multivariate Cox analysis, c Kit was an indicator of metastasis independent of 25 other concomitantly evaluated markers of prognosis. Logistic regression showed that c Kit ranked 10 out of 25 (P=0.041), and was included in a 10-marker signature that allowed 79.2% of the patients to be correctly classified in the metastatic or metastasis-free categories independently of hormone receptors and HER-2 status. Interestingly, c Kit was also a significant predictor of metastasis in node-negative tumours (2 out of 25 ranking, P<0.0001) and included in a six-marker signature of prognosis, correctly classifying 88.6% of the patients (P<0.0001). Conclusion: We concluded that, as assessed by quantitative immunohistochemistry, c Kit is an independent prognostic indicator that could also potentially serve as a target for specific therapy in breast carcinomas. PMID:19513067

  20. Low-grade adenosquamous carcinoma of the breast: A diagnostic and clinical challenge.

    PubMed

    Tan, Qing Ting; Chuwa, Esther Wee Lee; Chew, Sung Hock; Lim-Tan, Soo Kim; Lim, Swee Ho

    2015-07-01

    Adenosquamous carcinoma of the breast (ASBC) is a rare variant of metaplastic breast cancer with both glandular as well as squamous differentiation. Their lack of distinct imaging characteristics, sometimes subtle histological characteristics and overlapping features with other benign lesions pose a diagnostic challenge. Unlike other forms of metaplastic breast cancer, low-grade adenosquamous carcinoma (LGAC) tends to follow an indolent course with favourable prognosis. We reviewed eight cases of LGAC in our institution from June 2005 to March 2014. In six cases, LGAC was only found after excisional biopsy. In our patients, LGAC frequently co-existed with other forms of breast pathology. Two patients had incidental findings of LGAC alongside their primary malignant tumour (adenoid cystic carcinoma and invasive ductal carcinoma in one, four foci between 0.5 and 4.0 mm within a radial sclerosing lesion adjacent to a malignant phyllodes tumour in the other). A further four patients had LGAC within a complex sclerosing lesion. One patient had a focus of LGAC within a fibroadenoma. One had a focus of LGAC within a benign phyllodes tumour. None of the patients had evidence of nodal involvement. A high degree of suspicion is recommended as such lesions tend to be incidental histological findings within benign tumours or within complex sclerosing lesions. Although the risk of nodal and distant metastasis is low, the potential for local recurrence necessitates aggressive local excision with margin clearance. The role of axillary dissection has yet to be defined and routine sentinel node biopsy and axillary clearance may not be necessary in view of rarity of nodal metastasis in literature. Benefit from adjuvant radiotherapy or chemotherapy is not clearly defined. All eight patients in our study have shown no evidence of recurrence after definitive surgery but longer periods of surveillance is required. PMID:25986061

  1. 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

  2. Genomic Instability: A Stronger Prognostic Marker Than Proliferation for Early Stage Luminal Breast Carcinomas

    PubMed Central

    Vincent-Salomon, Anne; Benhamo, Vanessa; Gravier, Eléonore; Rigaill, Guillem; Gruel, Nadège; Robin, Stéphane; de Rycke, Yann; Mariani, Odette; Pierron, Gaëlle; Gentien, David; Reyal, Fabien; Cottu, Paul; Fourquet, Alain; Rouzier, Roman; Sastre-Garau, Xavier; Delattre, Olivier

    2013-01-01

    Background The accurate prognosis definition to tailor treatment for early luminal invasive breast carcinoma patients remains challenging. Materials and Methods Two hundred fourteen early luminal breast carcinomas were genotyped with single nucleotide polymorphisms (SNPs) array to determine the number of chromosomal breakpoints as a marker of genomic instability. Proliferation was assessed by KI67 (immunohistochemistry) and genomic grade index (transcriptomic analysis). IHC3 (IHC4 score for HER2 negative tumors) was also determined. Results In the training set (109 cases), the optimal cut-off was 34 breakpoints with a specificity of 0.94 and a sensitivity of 0.57 (Area under the curve (AUC): 0.81[0.71; 0.91]). In the validation set (105 cases), the outcome of patients with > 34 breakpoints (11 events / 22 patients) was poorer (logrank test p < 0.001; Relative Risk (RR): 3.7 [1.73; 7.92]), than that of patients with < 34 breakpoints (19 events / 83 patients).Whereas genomic grade and KI67 had a significant prognostic value in univariate analysis in contrast to IHC3 that failed to have a statistical significant prognostic value in this series, the number of breakpoints remained the only significant parameter predictive of outcome (RR: 3.47, Confidence Interval (CI [1.29; 9.31], p = 0.014)) in multivariate analysis . Conclusion Genomic instability, defined herein as a high number of chromosomal breakpoints, in early stage luminal breast carcinoma is a stronger prognostic marker than proliferation. PMID:24143191

  3. Epidemiologic study on carcinoma of the breast following irradiation for benign conditions in infancy and childhood

    SciTech Connect

    Oviedo, M.A.; Chmiel, J.S.; Curb, J.D.; Kautz, J.A.; Haenszel, W.; Scanlon, E.F.

    1983-07-01

    To investigate the relationship of irradiation during infancy and childhood to the subsequent development of carcinoma of the breast, 996 eligible patients were studied at Evanston Hospital, Evanston, Illinois, and Northwestern Memorial Hospital, Chicago. This was a case-control study, with those in the control group being selected from concurrent hospital admissions for nonmalignant surgical conditions. A second group consisting of those with benign biopsy results was also studied. The Mantel-Haenszel method of analysis, controlling for age and race, was used to estimate the approximate relative risk of carcinoma of the breast in the irradiated group compared with that for the nonirradiated group. The type of radiation history included radiotherapy for mastitis or enlarged thymus (nine patients), irradiation of the head and neck (69 patients), diagnostic fluoroscopies (ten patients) and miscellaneous irradiation (52 patients) for bursitis, eczema or keloid. Based upon the data obtained from the results of this study and its analysis, we conclude that there is little evidence of increased risk of carcinoma of the breast after irradiation about the head, neck and chest areas for benign conditions in the population being studied herein. Such a risk, if indeed it exists at all for this population, is estimated to be about 10 per cent.

  4. [Pros and cons of early cancer detection in breast carcinoma].

    PubMed

    Callies, R; Oberhoff, C

    2005-04-01

    Mammography is an appropriate method for the detection of early forms of cancer of the breast, and for reducing mortality. Whether this actually succeeds depends upon the quality of the early detection strategies employed. Currently the data on reduction of mortality by mammographic screening remain ambivalent. PMID:15887680

  5. 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

  6. Immunohistochemistry applied to the differential diagnosis between ductal and lobular carcinoma of the breast.

    PubMed

    de Deus Moura, Rafael; Wludarski, Sheila C L; Carvalho, Filomena M; Bacchi, Carlos E

    2013-01-01

    The distinction between classic lobular and ductal carcinoma, both in situ and invasive, has important therapeutic and management implications. Most ductal and lobular carcinomas are distinguished readily on hematoxylin-eosin-stained sections because of distinct histomorphologic features. In cases with ambiguous morphologic features, however, categorization in one or another type can be a challenge. Several immunohistochemical markers, including epithelial cadherin, p120, β-catenin, and low-molecular-weight and high-molecular-weight cytokeratins among others, have been introduced to help better discriminate between lobular neoplasia and ductal carcinoma. In this critical review of the literature, we comment about the usefulness and the limitations of these markers to improve the accuracy in the differential diagnosis of breast pathology. PMID:22595945

  7. Genetic Predisposition to In Situ and Invasive Lobular Carcinoma of the Breast

    PubMed Central

    Petridis, Christos; Brook, Mark N.; Nowinski, Salpie; Papouli, Efterpi; Fletcher, Olivia; Pinder, Sarah; Hanby, Andrew; Kohut, Kelly; Gorman, Patricia; Caneppele, Michele; Peto, Julian; dos Santos Silva, Isabel; Johnson, Nichola; Swann, Ruth; Dwek, Miriam; Perkins, Katherine-Anne; Gillett, Cheryl; Houlston, Richard; Ross, Gillian; De Ieso, Paolo; Southey, Melissa C.; Hopper, John L.; Provenzano, Elena; Apicella, Carmel; Wesseling, Jelle; Cornelissen, Sten; Keeman, Renske; Fasching, Peter A.; Jud, Sebastian M.; Ekici, Arif B.; Beckmann, Matthias W.; Kerin, Michael J.; Marme, Federick; Schneeweiss, Andreas; Sohn, Christof; Burwinkel, Barbara; Guénel, Pascal; Truong, Therese; Laurent-Puig, Pierre; Kerbrat, Pierre; Bojesen, Stig E.; Nordestgaard, Børge G.; Nielsen, Sune F.; Flyger, Henrik; Milne, Roger L.; Perez, Jose Ignacio Arias; Menéndez, Primitiva; Benitez, Javier; Brenner, Hermann; Dieffenbach, Aida Karina; Arndt, Volker; Stegmaier, Christa; Meindl, Alfons; Lichtner, Peter; Schmutzler, Rita K.; Lochmann, Magdalena; Brauch, Hiltrud; Fischer, Hans-Peter; Ko, Yon-Dschun; Nevanlinna, Heli; Muranen, Taru A.; Aittomäki, Kristiina; Blomqvist, Carl; Bogdanova, Natalia V.; Dörk, Thilo; Lindblom, Annika; Margolin, Sara; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M.; Chenevix-Trench, Georgia; Investigators, kConFab; Lambrechts, Diether; Weltens, Caroline; Van Limbergen, Erik; Hatse, Sigrid; Chang-Claude, Jenny; Rudolph, Anja; Seibold, Petra; Flesch-Janys, Dieter; Radice, Paolo; Peterlongo, Paolo; Bonanni, Bernardo; Volorio, Sara; Giles, Graham G.; Severi, Gianluca; Baglietto, Laura; Mclean, Catriona A.; Haiman, Christopher A.; Henderson, Brian E.; Schumacher, Fredrick; Le Marchand, Loic; Simard, Jacques; Goldberg, Mark S.; Labrèche, France; Dumont, Martine; Kristensen, Vessela; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Kauppila, Saila; Andrulis, Irene L.; Knight, Julia A.; Glendon, Gord; Mulligan, Anna Marie; Devillee, Peter; Tollenaar, Rob A. E. M.; Seynaeve, Caroline M.; Kriege, Mieke; Figueroa, Jonine; Chanock, Stephen J.; Sherman, Mark E.; Hooning, Maartje J.; Hollestelle, Antoinette; van den Ouweland, Ans M. W.; van Deurzen, Carolien H. M.; Li, Jingmei; Czene, Kamila; Humphreys, Keith; Cox, Angela; Cross, Simon S.; Reed, Malcolm W. R.; Shah, Mitul; Jakubowska, Anna; Lubinski, Jan; Jaworska-Bieniek, Katarzyna; Durda, Katarzyna; Swerdlow, Anthony; Ashworth, Alan; Orr, Nicholas; Schoemaker, Minouk; Couch, Fergus J.; Hallberg, Emily; González-Neira, Anna; Pita, Guillermo; Alonso, M. Rosario; Tessier, Daniel C.; Vincent, Daniel; Bacot, Francois; Bolla, Manjeet K.; Wang, Qin; Dennis, Joe; Michailidou, Kyriaki; Dunning, Alison M.; Hall, Per; Easton, Doug; Pharoah, Paul; Schmidt, Marjanka K.; Tomlinson, Ian; Garcia-Closas, Montserrat

    2014-01-01

    Invasive lobular breast cancer (ILC) accounts for 10–15% of all invasive breast carcinomas. It is generally ER positive (ER+) and often associated with lobular carcinoma in situ (LCIS). Genome-wide association studies have identified more than 70 common polymorphisms that predispose to breast cancer, but these studies included predominantly ductal (IDC) carcinomas. To identify novel common polymorphisms that predispose to ILC and LCIS, we pooled data from 6,023 cases (5,622 ILC, 401 pure LCIS) and 34,271 controls from 36 studies genotyped using the iCOGS chip. Six novel SNPs most strongly associated with ILC/LCIS in the pooled analysis were genotyped in a further 516 lobular cases (482 ILC, 36 LCIS) and 1,467 controls. These analyses identified a lobular-specific SNP at 7q34 (rs11977670, OR (95%CI) for ILC = 1.13 (1.09–1.18), P = 6.0×10−10; P-het for ILC vs IDC ER+ tumors = 1.8×10−4). Of the 75 known breast cancer polymorphisms that were genotyped, 56 were associated with ILC and 15 with LCIS at P<0.05. Two SNPs showed significantly stronger associations for ILC than LCIS (rs2981579/10q26/FGFR2, P-het = 0.04 and rs889312/5q11/MAP3K1, P-het = 0.03); and two showed stronger associations for LCIS than ILC (rs6678914/1q32/LGR6, P-het = 0.001 and rs1752911/6q14, P-het = 0.04). In addition, seven of the 75 known loci showed significant differences between ER+ tumors with IDC and ILC histology, three of these showing stronger associations for ILC (rs11249433/1p11, rs2981579/10q26/FGFR2 and rs10995190/10q21/ZNF365) and four associated only with IDC (5p12/rs10941679; rs2588809/14q24/RAD51L1, rs6472903/8q21 and rs1550623/2q31/CDCA7). In conclusion, we have identified one novel lobular breast cancer specific predisposition polymorphism at 7q34, and shown for the first time that common breast cancer polymorphisms predispose to LCIS. We have shown that many of the ER+ breast cancer predisposition loci also predispose to ILC, although there

  8. Genetic predisposition to in situ and invasive lobular carcinoma of the breast.

    PubMed

    Sawyer, Elinor; Roylance, Rebecca; Petridis, Christos; Brook, Mark N; Nowinski, Salpie; Papouli, Efterpi; Fletcher, Olivia; Pinder, Sarah; Hanby, Andrew; Kohut, Kelly; Gorman, Patricia; Caneppele, Michele; Peto, Julian; Dos Santos Silva, Isabel; Johnson, Nichola; Swann, Ruth; Dwek, Miriam; Perkins, Katherine-Anne; Gillett, Cheryl; Houlston, Richard; Ross, Gillian; De Ieso, Paolo; Southey, Melissa C; Hopper, John L; Provenzano, Elena; Apicella, Carmel; Wesseling, Jelle; Cornelissen, Sten; Keeman, Renske; Fasching, Peter A; Jud, Sebastian M; Ekici, Arif B; Beckmann, Matthias W; Kerin, Michael J; Marme, Federick; Schneeweiss, Andreas; Sohn, Christof; Burwinkel, Barbara; Guénel, Pascal; Truong, Therese; Laurent-Puig, Pierre; Kerbrat, Pierre; Bojesen, Stig E; Nordestgaard, Børge G; Nielsen, Sune F; Flyger, Henrik; Milne, Roger L; Perez, Jose Ignacio Arias; Menéndez, Primitiva; Benitez, Javier; Brenner, Hermann; Dieffenbach, Aida Karina; Arndt, Volker; Stegmaier, Christa; Meindl, Alfons; Lichtner, Peter; Schmutzler, Rita K; Lochmann, Magdalena; Brauch, Hiltrud; Fischer, Hans-Peter; Ko, Yon-Dschun; Nevanlinna, Heli; Muranen, Taru A; Aittomäki, Kristiina; Blomqvist, Carl; Bogdanova, Natalia V; Dörk, Thilo; Lindblom, Annika; Margolin, Sara; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M; Chenevix-Trench, Georgia; Investigators, Kconfab; Lambrechts, Diether; Weltens, Caroline; Van Limbergen, Erik; Hatse, Sigrid; Chang-Claude, Jenny; Rudolph, Anja; Seibold, Petra; Flesch-Janys, Dieter; Radice, Paolo; Peterlongo, Paolo; Bonanni, Bernardo; Volorio, Sara; Giles, Graham G; Severi, Gianluca; Baglietto, Laura; McLean, Catriona A; Haiman, Christopher A; Henderson, Brian E; Schumacher, Fredrick; Le Marchand, Loic; Simard, Jacques; Goldberg, Mark S; Labrèche, France; Dumont, Martine; Kristensen, Vessela; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Kauppila, Saila; Andrulis, Irene L; Knight, Julia A; Glendon, Gord; Mulligan, Anna Marie; Devillee, Peter; Tollenaar, Rob A E M; Seynaeve, Caroline M; Kriege, Mieke; Figueroa, Jonine; Chanock, Stephen J; Sherman, Mark E; Hooning, Maartje J; Hollestelle, Antoinette; van den Ouweland, Ans M W; van Deurzen, Carolien H M; Li, Jingmei; Czene, Kamila; Humphreys, Keith; Cox, Angela; Cross, Simon S; Reed, Malcolm W R; Shah, Mitul; Jakubowska, Anna; Lubinski, Jan; Jaworska-Bieniek, Katarzyna; Durda, Katarzyna; Swerdlow, Anthony; Ashworth, Alan; Orr, Nicholas; Schoemaker, Minouk; Couch, Fergus J; Hallberg, Emily; González-Neira, Anna; Pita, Guillermo; Alonso, M Rosario; Tessier, Daniel C; Vincent, Daniel; Bacot, Francois; Bolla, Manjeet K; Wang, Qin; Dennis, Joe; Michailidou, Kyriaki; Dunning, Alison M; Hall, Per; Easton, Doug; Pharoah, Paul; Schmidt, Marjanka K; Tomlinson, Ian; Garcia-Closas, Montserrat

    2014-04-01

    Invasive lobular breast cancer (ILC) accounts for 10-15% of all invasive breast carcinomas. It is generally ER positive (ER+) and often associated with lobular carcinoma in situ (LCIS). Genome-wide association studies have identified more than 70 common polymorphisms that predispose to breast cancer, but these studies included predominantly ductal (IDC) carcinomas. To identify novel common polymorphisms that predispose to ILC and LCIS, we pooled data from 6,023 cases (5,622 ILC, 401 pure LCIS) and 34,271 controls from 36 studies genotyped using the iCOGS chip. Six novel SNPs most strongly associated with ILC/LCIS in the pooled analysis were genotyped in a further 516 lobular cases (482 ILC, 36 LCIS) and 1,467 controls. These analyses identified a lobular-specific SNP at 7q34 (rs11977670, OR (95%CI) for ILC = 1.13 (1.09-1.18), P = 6.0 × 10(-10); P-het for ILC vs IDC ER+ tumors = 1.8 × 10(-4)). Of the 75 known breast cancer polymorphisms that were genotyped, 56 were associated with ILC and 15 with LCIS at P<0.05. Two SNPs showed significantly stronger associations for ILC than LCIS (rs2981579/10q26/FGFR2, P-het = 0.04 and rs889312/5q11/MAP3K1, P-het = 0.03); and two showed stronger associations for LCIS than ILC (rs6678914/1q32/LGR6, P-het = 0.001 and rs1752911/6q14, P-het = 0.04). In addition, seven of the 75 known loci showed significant differences between ER+ tumors with IDC and ILC histology, three of these showing stronger associations for ILC (rs11249433/1p11, rs2981579/10q26/FGFR2 and rs10995190/10q21/ZNF365) and four associated only with IDC (5p12/rs10941679; rs2588809/14q24/RAD51L1, rs6472903/8q21 and rs1550623/2q31/CDCA7). In conclusion, we have identified one novel lobular breast cancer specific predisposition polymorphism at 7q34, and shown for the first time that common breast cancer polymorphisms predispose to LCIS. We have shown that many of the ER+ breast cancer predisposition loci also predispose to ILC, although there is some heterogeneity

  9. SEMA6D Expression and Patient Survival in Breast Invasive Carcinoma

    PubMed Central

    Chen, Dongquan; Li, Yufeng; Wang, Lizhong; Jiao, Kai

    2015-01-01

    Breast cancer (BC) is the second most common cancer diagnosed in American women and is also the second leading cause of cancer death in women. Research has focused heavily on BC metastasis. Multiple signaling pathways have been implicated in regulating BC metastasis. Our knowledge of regulation of BC metastasis is, however, far from complete. Identification of new factors during metastasis is an essential step towards future therapy. Our labs have focused on Semaphorin 6D (SEMA6D), which was implicated in immune responses, heart development, and neurogenesis. It will be interesting to know SEMA6D-related genomic expression profile and its implications in clinical outcome. In this study, we examined the public datasets of breast invasive carcinoma from The Cancer Genome Atlas (TCGA). We analyzed the expression of SEMA6D along with its related genes, their functions, pathways, and potential as copredictors for BC patients' survival. We found 6-gene expression profile that can be used as such predictors. Our study provides evidences for the first time that breast invasive carcinoma may contain a subtype based on SEMA6D expression. The expression of SEMA6D gene may play an important role in promoting patient survival, especially among triple negative breast cancer patients. PMID:25973277

  10. An ultrastructural analysis of breast carcinoma presenting as isolated axillary adenopathy.

    PubMed Central

    Iglehart, J D; Ferguson, B J; Shingleton, W W; Sabiston, D C; Silva, J S; Fetter, B F; McCarty, K S

    1982-01-01

    Metastatic adenocarcinoma in the axillary lymph nodes of a female patient often originates from a primary tumor in the ipsilateral breast. Mastectomy may be recommended if adenocarcinoma is found in the axillary nodes even when the primary tumor is not clinically detectable. In these circumstances, the recommendation for mastectomy should be based on the firm histologic diagnosis of adenocarcinoma. In the present report, five female patients are discussed who presented with axillary lymphadenopathy without clinically evident breast masses or mammographic evidence of malignancy. Axillary lymph node biopsies, performed in each patient, were inconclusive after conventional light microscopic examination. Electron microscopy established the diagnosis of adenocarcinoma. These findings were complemented by sex steroid analyses of the tumors where possible. Each patient underwent ipsilateral mastectomy, and in each specimen an occult breast carcinoma was found. The necessity of making a precise tissue diagnosis in all cases of metastatic cancer from an unknown primary is stressed, and special techniques to accomplish this must be considered preoperatively. This is particularly important in the female patient with metastatic breast carcinoma in an isolated axillary lymph node, since ipsilateral mastectomy may be curative. Images Fig. 1a. Fig. 1b. Fig. 1c. PMID:6284071

  11. Ductal carcinoma in situ in a benign phyllodes tumor of breast: A rare presentation.

    PubMed

    Ghosh, Prithwijit; Saha, Kaushik

    2014-07-01

    Phyllodes tumor (PT) is an uncommon tumor of female breast. The tumor clinically, radiologically, cytologically as well as histologically can mimic fibroadenoma which is a common tumor of fibroepithelial group. Ductal carcinoma in situ (DCIS) in the epithelial component of PT is very rare. We report a rare case of intermediate grade DCIS arising in a benign PT in a 42-year-old lady. The patient presented with a small nodule in right breast along with serosanguineous discharge from nipple. Ultrasonography and cytology failed to distinguish between fibroadenoma and PT. Histopathological examination following wide local excision displayed the biphasic tumor comprising of benign looking cellular stroma and epithelial lining. It also demonstrated the foci of intermediate grade DCIS without any invasive component. Considering the clinicoradiological profile along with histopathological features, the diagnosis of DCIS in a benign PT of breast was made. PMID:25097439

  12. Dietary patterns and risk of ductal carcinoma of the breast: a factor analysis in Uruguay.

    PubMed

    Ronco, Alvaro L; De Stefani, Eduardo; Deneo-Pellegrini, Hugo; Boffetta, Paolo; Aune, Dagfinn; Silva, Cecilia; Landó, Gabriel; Luaces, María E; Acosta, Gisele; Mendilaharsu, María

    2010-01-01

    Breast cancer (BC) shows very high incidence rates in Uruguayan women. The present factor analysis of ductal carcinoma of the breast, the most frequent histological type of this malignancy both in Uruguay and in the World, was conducted at a prepaid hospital of Montevideo, Uruguay. We identified 111 cases with ductal BC and 222 controls with normal mammograms. A factor analysis was conducted using 39 food groups, allowing retention of six factors analyzed through logistic regression in order to obtain odds ratios (OR) associated with ductal BC. The low fat and non-alcoholic beverage patterns were inversely associated (OR=0.30 and OR=0.45, respectively) with risk. Conversely, the fatty cheese pattern was positively associated (OR=4.17) as well as the fried white meat (OR=2.28) and Western patterns (OR 2.13). Ductal BC shared similar dietary risk patterns as those identified by studies not discriminating between histologic type of breast cancer. PMID:21198261

  13. Tamoxifen Citrate, Letrozole, Anastrozole, or Exemestane With or Without Chemotherapy in Treating Patients With Invasive RxPONDER Breast Cancer

    ClinicalTrials.gov

    2016-09-15

    Ductal Breast Carcinoma In Situ; Estrogen Receptor and/or Progesterone Receptor Positive; HER2/Neu Negative; Invasive Breast Carcinoma; Multicentric Breast Carcinoma; Multifocal Breast Carcinoma; Synchronous Bilateral Breast Carcinoma

  14. Anomalous expression of P-cadherin in breast carcinoma. Correlation with E-cadherin expression and pathological features.

    PubMed Central

    Palacios, J.; Benito, N.; Pizarro, A.; Suárez, A.; Espada, J.; Cano, A.; Gamallo, C.

    1995-01-01

    Previous studies on the cell-cell adhesion molecules P- and E-cadherin have shown that P-cadherin is not expressed in breast cancer. In contrast, the expression of E-cadherin is a normal event in these tumors, but a reduction in the levels of this molecule in neoplastic cells is associated with the histological type, high histological grade, greater tumor size, and metastasis. The expression pattern of P- and E-cadherin were immunohistochemically studied in tissue sections from normal breast tissue, benign breast lesions, and 57 infiltrating breast carcinomas. Cadherin expression was analyzed in parallel with pathological features and the immunohistochemical expression of estrogen and progesterone receptors in breast carcinomas. P-cadherin was detected in the myoepithelial cells and E-cadherin in luminal epithelial cells from normal breast and benign breast lesions. P-cadherin expression was detected in 9 of 45 cases (20%) of infiltrating ductal carcinomas of no special type; none of the special histological types that were analyzed (7 infiltrating lobular carcinomas, 3 colloid carcinomas, and 2 infiltrating papillary carcinomas) expressed P-cadherin. In infiltrating ductal carcinomas, P-cadherin expression correlated significantly with a reduction in E-cadherin expression, histological grade (all cases were grade III tumors), and hormone receptor content (8 of 9 cases were estrogen and progesterone receptor negative). Although E-cadherin was not found in the 7 infiltrating lobular carcinomas, it was present in the remaining histological types and was preserved in 15 infiltrating ductal and 3 colloid and 2 papillary carcinomas and was reduced in 30 infiltrating ductal carcinomas. In addition, a reduction in E-cadherin expression was significantly associated with high histological grade and a lack of steroid hormone receptors in infiltrating ductal carcinomas. No apparent relationship was found between P- and E-cadherin expression and tumor size and axillary lymph

  15. Bcl-2 expression and triple negative profile in breast carcinoma.

    PubMed

    Kallel-Bayoudh, Imen; Hassen, Hanen Ben; Khabir, Abdelmajid; Boujelbene, Noureddine; Daoud, Jamel; Frikha, Mounir; Sallemi-Boudawara, Tahia; Aifa, Sami; Rebaï, Ahmed

    2011-12-01

    Many biomarkers for breast cancer prognosis have been proposed during the last two decades, among which HER2 and oestrogen receptors are of common use in routine clinical practice. However, in recent years, BCL2 has been recognized as an important prognostic parameter in human breast cancer, although its clinical utility is well established. The aim of this study was to examine the protein expression patterns of BCL2, HER2, oestrogen (ER) and progesterone receptors (PR) and to evaluate their correlation with survival and other prognostic parameters such as tumour size, histological grade and metastasis. We used a retrospective study including 84 Tunisian women with breast cancer. Immunohistochemistry was used to measure protein expression levels of several biomarkers. Association with conventional biopathological factors was analysed by SPSS (version13). The expression rates of BCL2, HER2, ER and PR were, respectively, 69, 62, 58.3 and 51.2%. In univariate analyses, BCL2 was highly correlated with both PR (P < 0.001) and ER (P = 0.006) and also with HER2 expression (P = 0.001). The triple negative profile showed a significant association with SBR (P = 0.016) and BCL2 expression (P = 0.02). In multivariate analyses, a significant association was maintained between BCL2 and both PR and ER (P = 0.02 and P = 0.004, respectively). Survival analysis showed that BCL2 expression was positively correlated with patients survival (P = 0.032). A Bayesian network analysis of all the variables confirmed the high value of BCL2 expression as a predictor of survival. As conclusion, BCL2 expression seems to be a very useful factor that should be in combination with HER2 and ER in breast cancer prognosis. PMID:20890735

  16. Perfusion analyses in advanced breast carcinoma during hyperthermia.

    PubMed

    Lagendijk, J J; Hofman, P; Schipper, J

    1988-01-01

    Blood flow in tumours and healthy tissue determines the ability of obtaining satisfactory temperature distributions in clinical hyperthermia, as well as the success of hyperthermia and radiation treatment. During the hyperthermia treatment, diagnostic data related to tissue blood flow can be determined by analysing the relationship between the amount of power absorbed in the tissue and the resulting temperature rise. The interpretation of the perfusion data (PERF) is highly complicated by the lack of an adequate theory to describe the heat transport in vascularized tissues. In vascularized breast tissues about 10 times as much power is needed to maintain therapeutic temperatures as is necessary in a stationary breast phantom. This large difference in maintenance power levels indicates the extreme importance of blood flow in tissue heat transport. PERF has been determined in 23 patients with advanced breast tumours. In this series (a) perfusion typically did not change during the stationary part of the individual hyperthermic sessions, (b) minimum tumour PERF was not related to tumour volume, and (c) there was no relation between tumour PERF and the ability to heat tumours. PERF can both increase and decrease after successful hyperthermia. PMID:3292667

  17. Accelerated Partial Breast Irradiation through Brachytherapy for Ductal Carcinoma in situ: Factors Influencing Utilization and Risks of Second Breast Tumors

    PubMed Central

    Liu, Ying; Schloemann, Derek T.; Lian, Min; Colditz, Graham A.

    2015-01-01

    Purpose To examine influencing factors and outcomes of accelerated partial breast irradiation through brachytherapy (APBIb) versus whole breast irradiation (WBI) for ductal carcinoma in situ (DCIS). Patients and Methods From the Surveillance Epidemiology and End Results program, we identified 40749 women who were diagnosed with first primary DCIS between 2002 and 2011 and treated with breast conserving surgery (BCS) and radiotherapy. A multi-level logistic regression analysis was performed to estimate odds ratios of APBIb use. Hazard ratios (HRs) of developing ipsilateral breast tumors (IBTs) and contralateral breast tumors (CBTs) were analyzed in 1962 patients with APBIb and 7203 propensity score-matched patients with WBI, using Cox proportional hazards regression. Results Overall, 2212 (4.5%) of 40749 women (the whole cohort) received APBIb. Factors associated with the increased use of APBIb included older age, non-Hispanic white race/ethnicity, smaller tumor size, hormone receptor positivity, comedo subtypes and urban residence. During the 46-month follow-up, 74 (0.8%) and 131 (1.4%) of 9165 propensity score-matched patients developed IBTs and CBTs, respectively. Compared with WBI, APBIb was associated with a significantly increased risk of IBTs (HR, 1.74; 95% CI, 1.06 to 2.85) but not CBTs (OR, 0.91; 95% CI, 0.59 to 1.41). Conclusion This population-based study suggests that APBIb use for DCIS was influenced by patient and tumor characteristics as well as urbanization of residence. We observed a moderately increased IBT risk associated with APBIb versus WBI, suggesting that APBIb should be used with caution for DCIS before data from randomized controlled trials with long-term followups are available. PMID:25893591

  18. Allelic imbalance study of 16q in human primary breast carcinomas using microsatellite markers.

    PubMed

    Dorion-Bonnet, F; Mautalen, S; Hostein, I; Longy, M

    1995-11-01

    The high incidence of allelic imbalance on the long arm of chromosome 16 in breast cancer suggests its involvement in the development and progression of the tumor. Several loss of heterozygosity (LOH) studies have led to the assignment of commonly deleted regions on 16q where tumor suppressor genes may be located. The most recurrent LOH regions have been 16q22.1 and 16q22.4-qter. The aim of this study was to gain further insight into the occurrence of one or multiple "smallest regions of overlap" on 16q in a new series of breast carcinomas. Hence, a detailed allelic imbalance map was constructed for 46 sporadic breast carcinomas, using 11 polymorphic microsatellite markers located on chromosome 16. Allelic imbalance of one or more markers on 16q was shown by 30 of the 46 tumors (65%). Among these 30 carcinomas, LOH on the long arm of chromosome 16 was detected at all informative loci in 19 (41%); 13 of them showed allelic imbalance on the long but not on the short arm, with the occurrence of variable "breakpoints" in the pericentromeric region. The partial allelic imbalance in 11 tumors involved either the 16q22.1-qter LOH region or interstitial LOH regions. A commonly deleted region was found between D16S421 and D16S289 on 16q22.1 in 29 of the 30 tumors. The present data argue in favor of an important involvement of a tumor suppressor gene mapping to 16q22.1 in the genesis or progression of breast cancer. PMID:8589033

  19. Enrichment methods to detect bone marrow micrometastases in breast carcinoma patients: clinical relevance

    PubMed Central

    Choesmel, Valérie; Pierga, Jean-Yves; Nos, Claude; Vincent-Salomon, Anne; Sigal-Zafrani, Brigitte; Thiery, Jean-Paul; Blin, Nathalie

    2004-01-01

    Introduction Improving technologies for the detection and purification of bone marrow (BM) micrometastatic cells in breast cancer patients should lead to earlier prognosis of the risk of relapse and should make it possible to design more appropriate therapies. The technique used has to overcome the challenges resulting from the small number of target cells (one per million hematopoietic cells) and the heterogeneous expression of micrometastatic cell markers. In the present study, we have assessed the clinical relevance of current methods aimed at detecting rare disseminated carcinoma cells. Methods BM aspirates from 32 carcinoma patients were screened for the presence of micrometastatic cells positive for epithelial cell adhesion molecule and positive for cytokeratins, using optimized immunodetection methods. A comparison with data obtained for 46 control BM aspirates and a correlation with the clinical status of patients were performed. Results We developed a sensitive and efficient immunomagnetic protocol for the enrichment of BM micrometastases. This method was used to divide 32 breast carcinoma patients into three categories according to their epithelial cell adhesion molecule status. These categories were highly correlated with the recently revised American Joint Committee on Cancer staging system for breast cancer, demonstrating the clinical relevance of this simple and reliable immunomagnetic technique. We also evaluated immunocytochemical detection of cytokeratin-positive cells and cytomorphological parameters. Immunocytochemistry-based methods for the detection of BM micrometastases did not provide any information about the clinical status of patients, but helped to refine the immunomagnetic data by confirming the presence of micrometastases in some cases. We also tested a new density gradient centrifugation system, able to enrich the tumor fraction of BM specimens by twofold to threefold as compared with standard Ficoll methods. Conclusion These improved

  20. Rapamycin Promotes Mouse 4T1 Tumor Metastasis that Can Be Reversed by a Dendritic Cell-Based Vaccine

    PubMed Central

    Lin, Tien-Jen; Liang, Wen-Miin; Hsiao, Pei-Wen; M. S, Pradeep; Wei, Wen-Chi; Lin, Hsin-Ting; Yin, Shu-Yi; Yang, Ning-Sun

    2015-01-01

    Suppression of tumor metastasis is a key strategy for successful cancer interventions. Previous studies indicated that rapamycin (sirolimus) may promote tumor regression activity or enhance immune response against tumor targets. However, rapamycin also exhibits immunosuppressant effects and is hence used clinically as an organ transplantation drug. We hypothesized that the immunosuppressive activities of rapamycin might also negatively mediate host immunity, resulting in promotion of tumor metastasis. In this study, the effects of rapamycin and phytochemical shikonin were investigated in vitro and in vivo in a 4T1 mouse mammary tumor model through quantitative assessment of immunogenic cell death (ICD), autophagy, tumor growth and metastasis. Tumor-bearing mice were immunized with test vaccines to monitor their effect on tumor metastasis. We found that intraperitoneal (ip) administration of rapamycin after a tumor-resection surgery drastically increased the metastatic activity of 4T1 tumors. Possible correlation of this finding to human cancers was suggested by epidemiological analysis of data from Taiwan’s National Health Insurance Research Database (NHIRD). Since our previous studies showed that modified tumor cell lysate (TCL)-pulsed, dendritic cell (DC)-based cancer vaccines can effectively suppress metastasis in mouse tumor models, we assessed whether such vaccines may help offset this rapamycin-promoted metastasis. We observed that shikonin efficiently induced ICD of 4T1 cells in culture, and DC vaccines pulsed with shikonin-treated TCL (SK-TCL-DC) significantly suppressed rapamycin-enhanced metastasis and Treg cell expansion in test mice. In conclusion, rapamycin treatment in mice (and perhaps in humans) promotes metastasis and the effect may be offset by treatment with a DC-based cancer vaccine. PMID:26426423

  1. Rapamycin Promotes Mouse 4T1 Tumor Metastasis that Can Be Reversed by a Dendritic Cell-Based Vaccine.

    PubMed

    Lin, Tien-Jen; Liang, Wen-Miin; Hsiao, Pei-Wen; M S, Pradeep; Wei, Wen-Chi; Lin, Hsin-Ting; Yin, Shu-Yi; Yang, Ning-Sun

    2015-01-01

    Suppression of tumor metastasis is a key strategy for successful cancer interventions. Previous studies indicated that rapamycin (sirolimus) may promote tumor regression activity or enhance immune response against tumor targets. However, rapamycin also exhibits immunosuppressant effects and is hence used clinically as an organ transplantation drug. We hypothesized that the immunosuppressive activities of rapamycin might also negatively mediate host immunity, resulting in promotion of tumor metastasis. In this study, the effects of rapamycin and phytochemical shikonin were investigated in vitro and in vivo in a 4T1 mouse mammary tumor model through quantitative assessment of immunogenic cell death (ICD), autophagy, tumor growth and metastasis. Tumor-bearing mice were immunized with test vaccines to monitor their effect on tumor metastasis. We found that intraperitoneal (ip) administration of rapamycin after a tumor-resection surgery drastically increased the metastatic activity of 4T1 tumors. Possible correlation of this finding to human cancers was suggested by epidemiological analysis of data from Taiwan's National Health Insurance Research Database (NHIRD). Since our previous studies showed that modified tumor cell lysate (TCL)-pulsed, dendritic cell (DC)-based cancer vaccines can effectively suppress metastasis in mouse tumor models, we assessed whether such vaccines may help offset this rapamycin-promoted metastasis. We observed that shikonin efficiently induced ICD of 4T1 cells in culture, and DC vaccines pulsed with shikonin-treated TCL (SK-TCL-DC) significantly suppressed rapamycin-enhanced metastasis and Treg cell expansion in test mice. In conclusion, rapamycin treatment in mice (and perhaps in humans) promotes metastasis and the effect may be offset by treatment with a DC-based cancer vaccine. PMID:26426423

  2. Metastatic canine mammary carcinomas can be identified by a gene expression profile that partly overlaps with human breast cancer profiles

    PubMed Central

    2010-01-01

    Background Similar to human breast cancer mammary tumors of the female dog are commonly associated with a fatal outcome due to the development of distant metastases. However, the molecular defects leading to metastasis are largely unknown and the value of canine mammary carcinoma as a model for human breast cancer is unclear. In this study, we analyzed the gene expression signatures associated with mammary tumor metastasis and asked for parallels with the human equivalent. Methods Messenger RNA expression profiles of twenty-seven lymph node metastasis positive or negative canine mammary carcinomas were established by microarray analysis. Differentially expressed genes were functionally characterized and associated with molecular pathways. The findings were also correlated with published data on human breast cancer. Results Metastatic canine mammary carcinomas had 1,011 significantly differentially expressed genes when compared to non-metastatic carcinomas. Metastatic carcinomas had a significant up-regulation of genes associated with cell cycle regulation, matrix modulation, protein folding and proteasomal degradation whereas cell differentiation genes, growth factor pathway genes and regulators of actin organization were significantly down-regulated. Interestingly, 265 of the 1,011 differentially expressed canine genes are also related to human breast cancer and, vice versa, parts of a human prognostic gene signature were identified in the expression profiles of the metastatic canine tumors. Conclusions Metastatic canine mammary carcinomas can be discriminated from non-metastatic carcinomas by their gene expression profiles. More than one third of the differentially expressed genes are also described of relevance for human breast cancer. Many of the differentially expressed genes are linked to functions and pathways which appear to be relevant for the induction and maintenance of metastatic progression and may represent new therapeutic targets. Furthermore, dogs

  3. Clinical features and treatment of squamous cell carcinoma of the breast

    PubMed Central

    Zhang, Ximei; Zhang, Baozhong; Zang, Fenglin; Zhao, Lujun; Yuan, Zhiyong; Wang, Ping

    2016-01-01

    Objectives Data on breast squamous cell carcinoma (SCC) are rare. The aim of this study was to analyze the clinical characteristics and to explore the rational treatment of patients with breast SCC. Patients and methods We conducted a retrospective review of breast SCC cases treated at our center from 1966 to 2014. The majority of these patients received primary surgery followed by adjuvant chemoradiotherapy, whilst four elderly patients had lumpectomy only. Results Patients with breast SCC were usually women, and large masses, large proportion of early stage disease, low levels of estrogen receptor expression, less frequent axillary lymph nodes involvement, and unfavorable prognosis were common. The 5-year overall survival and progression-free survival of all patients were 67.2% and 57.8%, respectively. Axillary nodal involvement was a significant prognostic factor for survival. Conclusion The current results indicated that breast SCC is clinically aggressive and the outcomes were poor. Distant metastasis was the main failure pattern. New strategies will be needed because of the poor outcomes. PMID:27313463

  4. Identification of angiogenesis in primary breast carcinoma according to the image analysis.

    PubMed

    Kim, Sung-Won; Park, Sung-Shin; Ahn, Soo-Jung; Chung, Ki-Wook; Moon, Woo Kyung; Im, Jung-Gi; Yeo, Jeong Seok; Chung, June-Key; Noh, Dong-Young

    2002-07-01

    Tumor angiogenesis may be an independent prognostic factor for breast cancer survival. However, we can get the angiogenic property of the breast cancer only after the removal of breast tissue. To get this information before surgical resection of the tumor, we evaluated 29 breast carcinoma patients with Tc-99m MIBI scintimammography and power Doppler ultrasound (US) with a microbubble contrast agent preoperatively and compare their results with intratumoral microvessel density (IMD) and reverse transcriptase-polymerase chain reaction (RT-PCR) of VEGF mRNA. IMD was well correlated with VEGF121 (r = 0.220, P = 0.024) and VEGF165 (r = 0.419, P = 0.046) mRNA level of the tumor. Power Doppler US grading of the tumor is well correlated with IMD (r = 0.552, P = 0.033). However, early uptake and washout index calculated from Tc-99m MIBI scintimammography showed no correlation with IMD or VEGF mRNA level, while washout index was inversely correlated with power Doppler US grading (r = -0.945, P = 0.001). In conclusion, the preoperative evaluation of breast cancer with power Doppler US with a microbubble contrast agent could predict tumor angiogenesis. Tc-99m MIBI scintimammography needs further study to use it as an image analysis for angiogenesis. PMID:12186372

  5. Expression of c-erbB3 protein in primary breast carcinomas.

    PubMed Central

    Naidu, R.; Yadav, M.; Nair, S.; Kutty, M. K.

    1998-01-01

    Expression of c-erbB3 protein was investigated in 104 primary breast carcinomas comprising nine comedo ductal carcinoma in situ (DCIS), 91 invasive ductal carcinomas and four invasive lobular carcinomas using two monoclonal antibodies, RTJ1 and RTJ2. Of the 91 invasive ductal carcinomas, seven contained the comedo DCIS component adjacent to the invasive component. An immunohistochemical technique was used to evaluate the association between expression of c-erbB3 and clinical parameters and tumour markers such as epidermal growth factor receptor (EGFR), c-erbB2, cathepsin-D and p53 in archival formalin-fixed paraffin-embedded tumour tissues. Our results indicated that RTJ1 and RTJ2 gave identical staining patterns and concordant results. It was found that the overexpression of c-erbB3 protein was observed in 67% (6/9) of comedo DCIS, 52% (44/84) of invasive ductal carcinomas, 71% (5/7) of carcinomas containing both the in situ and invasive lesions and 25% (1/4) of invasive lobular carcinomas. A significant relationship (P < 0.05) was observed between strong immunoreactivity of c-erbB3 protein and histological grade, EGFR and cathepsin-D, but not with expression of c-erbB2, p53, oestrogen receptor status, lymph node metastases or age of patient. However, we noted that a high percentage of oestrogen receptor-negative tumours (59%), lymph node-positive tumours (63%) and c-erbB2 (63%) were strongly positive for c-erbB3 protein. We have also documented that a high percentage of EGFR (67%), c-erbB2 (67%), p53 (75%) and cathepsin-D-positive DCIS (60%) were strongly positive for c-erbB3. These observations suggest that overexpression of c-erbB3 protein could play an important role in tumour progression from non-invasive to invasive and, also, that it may have the potential to be used as a marker for poor prognosis of breast cancer. Images Figure 1 Figure 2 PMID:9823984

  6. 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

  7. Human homologue of cement gland protein, a novel metastasis inducer associated with breast carcinomas.

    PubMed

    Liu, Dong; Rudland, Philip S; Sibson, D Ross; Platt-Higgins, Angela; Barraclough, Roger

    2005-05-01

    A suppression subtractive cDNA library representing mRNAs expressed at a higher level in the malignant human breast cancer cell line, MCF-7, relative to a benign breast tumor-derived cell line, Huma 123, contained a cDNA, M36, which was expressed in estrogen receptor alpha (ERalpha)-positive breast carcinoma cell lines but not in cell lines from normal/benign/ERalpha-negative malignant breast lesions. M36 cDNA had an identical coding sequence to anterior gradient 2 (AGR2), the human homologue of the cement gland-specific gene (Xenopus laevis). Screening of breast tumor specimens using reverse transcription-PCR and immunocytochemistry with affinity-purified anti-AGR2 antibodies showed that the presence of AGR2 mRNA and protein were both statistically significantly associated with ERalpha-positive carcinomas (P = 0.007, Fisher's exact test) and with malignancy (P < or = 0.025). When an expression vector for AGR2 cDNA was introduced into benign nonmetastatic rat mammary tumor cells, and three separate clones and two pools of cells were transferred to the mammary glands of syngeneic hosts, there were no consistent differences in the mean latent periods of tumor formation. However, metastases occurred in the lungs of animals receiving the AGR2 transfectants in 77% to 92% of animals with primary tumors (P = 0.0001) compared with no metastases in the control groups. The AGR2 transfectants exhibited enhanced rates of adhesion to a plastic substratum and extracellular AGR2 enhanced the rate of attachment of AGR2-negative but not AGR2-positive cells. These experiments are the first to link mechanistically the developmental gene product, AGR2, with metastasis in vivo. PMID:15867376

  8. Mass Spectrometric Characterization of Protein Structure Details Refines the Proteome Signature for Invasive Ductal Breast Carcinoma

    NASA Astrophysics Data System (ADS)

    Röwer, Claudia; Koy, Cornelia; Hecker, Michael; Reimer, Toralf; Gerber, Bernd; Thiesen, Hans-Jürgen; Glocker, Michael O.

    2011-03-01

    Early diagnosis as well as individualized therapies are necessary to reduce the mortality of breast cancer, and personalized patient care strategies rely on novel prognostic or predictive factors. In this study, with six breast cancer patients, 2D gel analysis was applied for studying protein expression differences in order to distinguish invasive ductal breast carcinoma, the most frequent breast tumor subtype, from control samples. In total, 1203 protein spots were assembled in a 2D reference gel. Differentially abundant spots were subjected to peptide mass fingerprinting for protein identification. Twenty proteins with their corresponding 38 differentially expressed 2D gel spots were contained in our previously reported proteome signature, suggesting that distinct protein forms were contributing. In-depth MS/MS measurements enabled analyses of protein structure details of selected proteins. In protein spots that significantly contributed to our signature, we found that glyceraldehyde-3-phosphate dehydrogenase was N-terminally truncated, pyruvate kinase M2 and nucleoside diphosphate kinase A but not other isoforms of these proteins were of importance, and nucleophosmin phosphorylation at serine residues 106 and 125 were clearly identified. Principle component analysis and hierarchical clustering with normalized quantitative data from the 38 spots resulted in accurate separation of tumor from control samples. Thus, separation of tissue samples as in our initial proteome signature could be confirmed even with a different proteome analysis platform. In addition, detailed protein structure investigations enabled refining our proteome signature for invasive ductal breast carcinoma, opening the way to structure-/function studies with respect to disease processes and/or therapeutic intervention.

  9. Prospective Multicenter Trial Evaluating Balloon-Catheter Partial-Breast Irradiation for Ductal Carcinoma in Situ

    SciTech Connect

    Abbott, Andrea M.; Portschy, Pamela R.; Lee, Chung; Le, Chap T.; Han, Linda K.; Washington, Tara; Kinney, Michael; Bretzke, Margit; Tuttle, Todd M.

    2013-11-01

    Purpose: To determine outcomes of accelerated partial-breast irradiation (APBI) with MammoSite in the treatment of ductal carcinoma in situ (DCIS) after breast-conserving surgery. Methods and Materials: We conducted a prospective, multicenter trial between 2003 and 2009. Inclusion criteria included age >18 years, core needle biopsy diagnosis of DCIS, and no prior breast cancer history. Patients underwent breast-conserving surgery plus MammoSite placement. Radiation was given twice daily for 5 days for a total of 34 Gy. Patients were evaluated for development of toxicities, cosmetic outcome, and ipsilateral breast tumor recurrence (IBTR). Results: A total of 41 patients (42 breasts) completed treatment in the study, with a median follow up of 5.3 years. Overall, 28 patients (68.3%) experienced an adverse event. Skin changes and pain were the most common adverse events. Cosmetic outcome at 6 months was judged excellent/good by 100% of physicians and by 96.8% of patients. At 12 months, 86.7% of physicians and 92.3% of patients rated the cosmetic outcome as excellent/good. Overall, 4 patients (9.8%) developed an IBTR (all DCIS), with a 5-year actuarial rate of 11.3%. All IBTRs were outside the treatment field. Among patients with IBTRs, the mean time to recurrence was 3.2 years. Conclusions: Accelerated partial-breast irradiation using MammoSite seems to provide a safe and cosmetically acceptable outcome; however, the 9.8% IBTR rate with median follow-up of 5.3 years is concerning. Prospective randomized trials are necessary before routine use of APBI for DCIS can be recommended.

  10. Investigative and extrapolative role of microRNAs’ genetic expression in breast carcinoma

    PubMed Central

    Usmani, Ambreen; Shoro, Amir Ali; Shirazi, Bushra; Memon, Zahida

    2016-01-01

    MicroRNAs (miRs) are non-coding ribonucleic acids consisting of about 18-22 nucleotide bases. Expression of several miRs can be altered in breast carcinomas in comparison to healthy breast tissue, or between various subtypes of breast cancer. These are regulated as either oncogene or tumor suppressors, this shows that their expression is misrepresented in cancers. Some miRs are specifically associated with breast cancer and are affected by cancer-restricted signaling pathways e.g. downstream of estrogen receptor-α or HER2/neu. Connection of multiple miRs with breast cancer, and the fact that most of these post transcript structures may transform complex functional networks of mRNAs, identify them as potential investigative, extrapolative and predictive tumor markers, as well as possible targets for treatment. Investigative tools that are currently available are RNA-based molecular techniques. An additional advantage related to miRs in oncology is that they are remarkably stable and are notably detectable in serum and plasma. Literature search was performed by using database of PubMed, the keywords used were microRNA (52 searches) AND breast cancer (169 searches). PERN was used by database of Bahria University, this included literature and articles from international sources; 2 articles from Pakistan on this topic were consulted (one in international journal and one in a local journal). Of these, 49 articles were shortlisted which discussed relation of microRNA genetic expression in breast cancer. These articles were consulted for this review. PMID:27375730

  11. Investigative and extrapolative role of microRNAs' genetic expression in breast carcinoma.

    PubMed

    Usmani, Ambreen; Shoro, Amir Ali; Shirazi, Bushra; Memon, Zahida

    2016-01-01

    MicroRNAs (miRs) are non-coding ribonucleic acids consisting of about 18-22 nucleotide bases. Expression of several miRs can be altered in breast carcinomas in comparison to healthy breast tissue, or between various subtypes of breast cancer. These are regulated as either oncogene or tumor suppressors, this shows that their expression is misrepresented in cancers. Some miRs are specifically associated with breast cancer and are affected by cancer-restricted signaling pathways e.g. downstream of estrogen receptor-α or HER2/neu. Connection of multiple miRs with breast cancer, and the fact that most of these post transcript structures may transform complex functional networks of mRNAs, identify them as potential investigative, extrapolative and predictive tumor markers, as well as possible targets for treatment. Investigative tools that are currently available are RNA-based molecular techniques. An additional advantage related to miRs in oncology is that they are remarkably stable and are notably detectable in serum and plasma. Literature search was performed by using database of PubMed, the keywords used were microRNA (52 searches) AND breast cancer (169 searches). PERN was used by database of Bahria University, this included literature and articles from international sources; 2 articles from Pakistan on this topic were consulted (one in international journal and one in a local journal). Of these, 49 articles were shortlisted which discussed relation of microRNA genetic expression in breast cancer. These articles were consulted for this review. PMID:27375730

  12. Management of Adenoid Cystic Carcinoma of the Breast: A Rare Cancer Network Study

    SciTech Connect

    Khanfir, Kaouthar; Kallel, Adel; Villette, Sylviane; Belkacemi, Yazid; Vautravers, Claire; Nguyen, TanDat; Miller, Robert; Li Yexiong; Taghian, Alphonse G.; Boersma, Liesbeth; Poortmans, Philip; Goldberg, Hadassah; Vees, Hansjorg; Senkus, Elzbieta; Igdem, Sefik; Ozsahin, Mahmut; Jeanneret Sozzi, Wendy

    2012-04-01

    Background: Mammary adenoid cystic carcinoma (ACC) is a rare breast cancer. The aim of this retrospective study was to assess prognostic factors and patterns of failure, as well as the role of radiation therapy (RT), in ACC. Methods: Between January 1980 and December 2007, 61 women with breast ACC were treated at participating centers of the Rare Cancer Network. Surgery consisted of lumpectomy in 41 patients and mastectomy in 20 patients. There were 51(84%) stage pN0 and 10 stage cN0 (16%) patients. Postoperative RT was administered to 40 patients (35 after lumpectomy, 5 after mastectomy). Results: With a median follow-up of 79 months (range, 6-285), 5-year overall and disease-free survival rates were 94% (95% confidence interval [CI], 88%-100%) and 82% (95% CI, 71%-93%), respectively. The 5-year locoregional control (LRC) rate was 95% (95% CI, 89%-100%). Axillary lymph node dissection or sentinel node biopsy was performed in 84% of cases. All patients had stage pN0 disease. In univariate analysis, survival was not influenced by the type of surgery or the use of postoperative RT. The 5-year LRC rate was 100% in the mastectomy group versus 93% (95% CI, 83%-100%) in the breast-conserving surgery group, respectively (p = 0.16). For the breast-conserving surgery group, the use of RT significantly correlated with LRC (p = 0.03); the 5-year LRC rates were 95% (95% CI, 86%-100%) for the RT group versus 83% (95% CI, 54%-100%) for the group receiving no RT. No local failures occurred in patients with positive margins, all of whom received postoperative RT. Conclusion: Breast-conserving surgery is the treatment of choice for patients with ACC breast cancer. Axillary lymph node dissection or sentinel node biopsy might not be recommended. Postoperative RT should be proposed in the case of breast-conserving surgery.

  13. Breast metastases from a Renal Cell Carcinoma. A case report and review of the literature☆

    PubMed Central

    Falco, G.; Buggi, F.; Sanna, P.A.; Dubini, A.; Folli, S.

    2014-01-01

    INTRODUCTION Metastases to the breast from extra-mammary tumors are uncommon and few sporadic cases are reported in the international literature. An accurate differential diagnosis of secondary cancer is mandatory because both prognosis and treatment differ with respect to primary breast tumors. PRESENTATION OF CASE We present the case of a 70-year-old woman with an isolated metastasis to the breast occuring 9 years after undergoing a nephrectomy for Renal Cell Carcinoma (RCC). Clinical examination revealed a palpable and mobile mass in the right breast with an enlarged ipsilateral axillary lymph node. Mammographic findings showed a dense, well circumscribed solid mass and the breast ultrasonography findings were those of a hypoechoic homogeneous solid nodule with no posterior attenuation but with prominent peripheral vascularity. A tru-cut biopsy was conclusive for a metastatic deposit by RCC. A whole-body CT scan showed no evidence of further recurrences. The patient underwent metastasectomy and exeresis of the papable lymphnode. DISCUSSION In patients with former surgery for RCC, a diagnosis based on a preoperative biopsy allows to indicate the proper surgical treatment: in facts, as compared to primary breast tumors treatment, the rationale to pursue wide surgical margins is pointless in cases of metastases and, similarly, the biopsy of the sentinel lymphnode is void of sense due to the lack of its physiopathological prerequisite. CONCLUSION We suggest to consider a micro-histological biopsy of any new breast lesion appearing in a patient with a history of treatment for RCC. Prompt diagnosis is necessary to choose the right treatment. PMID:24632302

  14. Expression of E2F-4 in invasive breast carcinomas is associated with poor prognosis.

    PubMed

    Rakha, Emad A; Pinder, Sarah E; Paish, E Claire; Robertson, John F; Ellis, Ian O

    2004-07-01

    The E2F family of transcription factors plays a key role in the control of cellular proliferation and apoptosis. Some family members act as oncogenes and others act as tumour suppressor genes (TSGs), behaviour which appears to be tissue-specific. E2F-4 is a member of the E2F family, located at chromosome band 16q22.1, that shows frequent deletion in breast cancer, suggesting that it may function as a TSG in breast carcinogenesis. In the present study, the expression of E2F-4 was assessed immunohistochemically on paraffin wax sections from 265 breast carcinomas and expression was compared with both clinicopathological variables and disease outcome in an attempt to identify its possible role as a TSG and to assess its prognostic value, if any, in breast cancer. E2F-4 protein expression was detected in the nuclei and in the cytoplasm of normal and malignant breast epithelial cells. In the malignant tissues, no significant loss or decrease of expression was seen in association with any specific tumour type. There was a correlation between increased nuclear expression of E2F-4 and indicators of poor prognosis including larger tumour size (p = 0.000), grade 3 lesions (p = 0.033), lymph node stage (p = 0.037), and poorer Nottingham prognostic index group (p = 0.003). Increased immunoreactivity was also seen in association with the development of recurrent disease (p = 0.004), distant metastasis (p = 0.001), and poorer outcome including poorer overall survival time (p = 0.002) and shorter disease-free interval (p = 0.001). In multivariate analysis, E2F-4 was of independent prognostic significance along with grade and lymph node stage. These results suggest that E2F-4 may play a role in breast cancer progression and that increased nuclear expression is associated with more advanced tumours with poor outcomes. E2F-4 appears to have an oncogenic role rather than a tumour suppressor role in breast carcinogenesis and, hence, it is not the gene targeted by 16q22.1 loss in breast

  15. Epigenetic reversion of breast carcinoma phenotype is accompaniedby DNA sequestration

    SciTech Connect

    Sandal, Tone; Valyi-Nagy, Klara; Spencer, Virginia A.; Folberg,Robert; Bissell, Mina J.; Maniotis, Andrew J.

    2006-07-19

    The importance of microenvironment and context in regulation of tissue-specific genes is finally well established. DNA exposure to, or sequestration from, nucleases can be used to detect differences in higher order chromatin structure in intact cells without disturbing cellular or tissue architecture. To investigate the relationship between chromatin organization and tumor phenotype, we utilized an established 3-D assay where normal and malignant human breast cells can be easily distinguished by the morphology of the structures they make (acinus-like vs tumor-like, respectively). We show that these phenotypes can be distinguished also by sensitivity to AluI digestion where the malignant cells are resistant to digestion relative to non-malignant cells. Reversion of the T4-2 breast cancer cells by either cAMP analogs, or a phospatidylinositol 3-kinase (P13K) inhibitor not only reverted the phenotype, but also the chromatin sensitivity to AluI. By using different cAMP-analogs, we show that the cAMP-induced phenotypic reversion, polarization, and shift in DNA organization act through a cAMP-dependent-protein-kinase A-coupled signaling pathway. Importantly, inhibitory antibody to fibronectin also reverted the malignant phenotype, polarized the acini, and changed chromatin sequestration. These experiments show not only that modifying the tumor microenvironment can alter the organization of tumor cells but also that architecture of the tissues and the global chromatin organization are coupled and yet highly plastic.

  16. Image cytometry of estrogen receptors in breast carcinomas.

    PubMed

    Cohen, O; Brugal, G; Seigneurin, D; Demongeot, J

    1988-11-01

    A significant level of estrogen receptors (ER) in breast cancer cells is an indication of tumor differentiation and suggests that a homeostatic control of cell growth may persist in these cancers. In medical practice, the Dextran-coated charcoal assays (DCCA) are still the most frequently used test to characterize patients having ER-positive malignant breast tumors and for whom hormonal therapy is justified. Nevertheless, this routine biochemical technique is not satisfactory because it is a broad method unsuitable for revealing receptor tissue heterogeneity. However, immunocytochemical labeling, such as the ER-ICA method, which involves a monoclonal antibody linked to peroxidase, is a specific reaction for this purpose but which until now was not quantitative. The present study uses an original cell preparation technique combining the PAP reaction with toluidine blue counterstain for image analysis on the SAMBA system. Special software has been developed for the quantitative analysis of immunocytochemistry in cancers. Results obtained showed a high correlation between the DCCA values and the score derived from the mean ER concentration per positive tumor cell and the labeling index. In addition, intracell and intratumor heterogeneity can be displayed according to several parameters and were shown to vary according to tumor and to antiestrogen (Tamoxifen) presurgical therapy. PMID:2463134

  17. 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; ...

  18. Squamous Cell Carcinoma In Situ of the Breast: Report of a Case.

    PubMed

    Arafah, Maria; Ginter, Paula S; Taylor, David C; Hoda, Syed A

    2016-09-01

    We present the case of a 73-year-old woman with pure squamous cell carcinoma in situ of the left breast. This non-invasive malignancy exhibited pure squamous type of architectural and cytologic features without any evidence of glandular differentiation either in the initial needle core biopsy or in the subsequently performed excisional biopsy and simple mastectomy. The tumor spanned 1.6 cm, involved numerous ducts and terminal ducts and extended into lobules, and was characterized by keratinizing squamous cells with intermediate-grade nuclei. Intercellular bridges extended between the malignant squamous cells. Keratinous debris with "pearl" formation was evident in most involved glands. No invasive carcinoma was identified. There was no evidence of metastatic disease in the ipsilateral sentinel lymph nodes. Thus far, only three cases of squamous cell carcinoma in situ of the breast have been reported in one series-none of which showed any evidence of recurrent or metastatic disease at last follow-up. In our case, treated exclusively by surgery, there was no evidence of disease 11 years after diagnosis. PMID:27279634

  19. Loss of heterozygosity on chromosomes 17 and 18 in breast carcinoma: two additional regions identified.

    PubMed Central

    Cropp, C S; Lidereau, R; Campbell, G; Champene, M H; Callahan, R

    1990-01-01

    The loss of heterozygosity (LOH) at specific regions of the human genome in tumor DNA is recognized as evidence for a tumor-suppressor gene located within the corresponding region of the homologous chromosome. Restriction fragment length polymorphism analysis of a panel of primary human breast tumor DNAs has led to the identification of two additional regions on chromosomes 17q and 18q that frequently are affected by LOH. Deletions of each of these regions have a significant correlation with clinical parameters that are associated with aggressive breast carcinomas. Previous restriction fragment length polymorphism analysis of this panel of tumors has uncovered several other frequently occurring mutations. LOH on chromosome 18q frequently occurs in tumors with concomitant LOH of loci on chromosomes 17p and 11p. Similarly, tumors having LOH on 17q also have LOH on chromosomes 1p and 3p. This suggests that certain combinations of mutations may collaborate in the development and malignant progression of breast carcinomas. Images PMID:1977164

  20. Multiphoton microscopic imaging of fibrotic focus in invasive ductal carcinoma of the breast

    NASA Astrophysics Data System (ADS)

    Chen, Sijia; Nie, Yuting; Lian, Yuane; Wu, Yan; Fu, Fangmeng; Wang, Chuan; Zhuo, Shuangmu; Chen, Jianxin

    2014-11-01

    During the proliferation of breast cancer, the desmoplastic can evoke a fibrosis response by invading healthy tissue. Fibrotic focus (FF) in invasive ductal carcinoma (IDC) of the breast had been reported to be associated with significantly poorer survival rate than IDC without FF. As an important prognosis indicator, it's difficult to obtain the exact fibrotic information from traditional detection method such as mammography. Multiphoton imaging based on two-photon excited fluorescence (TPEF) and second-harmonic generation (SHG) has been recently employed for microscopic examination of unstained tissue. In this study, multiphoton microscopy (MPM) was used to image the fibrotic focus in invasive ductal carcinoma tissue. The morphology and distribution of collagen in fibrotic focus can be demonstrated by the SHG signal. Variation of collagen between IDC with and without FF will be examined and further characterized, which may be greatly related to the metastasis of breast cancer. Our result suggested that the MPM can be efficient in identifying and locating the fibrotic focus in IDC. Combining with the pathology analysis and other detecting methods, MPM owns potential in becoming an advanced histological tool for detecting the fibrotic focus in IDC and collecting prognosis information, which may guide the subsequent surgery option and therapy procedure for patients.

  1. Breastfeeding and Immunohistochemical Expression of ki-67, p53 and BCL2 in Infiltrating Lobular Breast Carcinoma

    PubMed Central

    Gonzalez-Sistal, Angel; Baltasar-Sánchez, Alicia; Menéndez, Primitiva; Arias, Jose Ignacio; Ruibal, Álvaro

    2016-01-01

    Background/Aim Invasive lobular breast carcinoma is the second most common type of breast cancer after invasive ductal carcinoma. According to the American Cancer Society, more than 180,000 women in the United States find out they have invasive breast cancer each year. Personal history of breast cancer and certain changes in the breast are correlated with an increased breast cancer risk. The aim of this work was to analyze breastfeeding in patients with infiltrating lobular breast carcinoma, in relation with: 1) clinicopathological parameters, 2) hormonal receptors and 3) tissue-based tumor markers Materials and Methods The study included 80 women with ILC, 46 of which had breastfeed their children. Analyzed parameters were: age, tumor size, axillary lymph node (N), distant metastasis (M), histological grade (HG), estrogen receptor (ER), progesterone receptor (PR), androgen receptor (AR), Ki-67, p53 and BCL2 Results ILC of non-lactating women showed a larger (p = 0.009), lymph node involvement (p = 0.051) and distant metastasis (p = 0.060). They were also more proliferative tumors measured by Ki-67 (p = 0.053). Breastfeeding history did not influence the subsequent behavior of the tumor regardless of histological subtype Conclusion Lactation seems to influence the biological characteristics of ILC defining a subgroup with more tumor size, axillary lymph node involvement, distant metastasis and higher proliferation measured by ki-67 expression. PMID:26963620

  2. Detecting gas‐induced vasomotor changes via blood oxygenation level‐dependent contrast in healthy breast parenchyma and breast carcinoma

    PubMed Central

    Wallace, Tess E.; Patterson, Andrew J.; Abeyakoon, Oshaani; Bedair, Reem; Manavaki, Roido; McLean, Mary A.; O'Connor, James P.B.; Graves, Martin J.

    2016-01-01

    Purpose To evaluate blood oxygenation level‐dependent (BOLD) contrast changes in healthy breast parenchyma and breast carcinoma during administration of vasoactive gas stimuli. Materials and Methods Magnetic resonance imaging (MRI) was performed at 3T in 19 healthy premenopausal female volunteers using a single‐shot fast spin echo sequence to acquire dynamic T 2‐weighted images. 2% (n = 9) and 5% (n = 10) carbogen gas mixtures were interleaved with either medical air or oxygen in 2‐minute blocks, for four complete cycles. A 12‐minute medical air breathing period was used to determine background physiological modulation. Pixel‐wise correlation analysis was applied to evaluate response to the stimuli in breast parenchyma and these results were compared to the all‐air control. The relative BOLD effect size was compared between two groups of volunteers scanned in different phases of the menstrual cycle. The optimal stimulus design was evaluated in five breast cancer patients. Results Of the four stimulus combinations tested, oxygen vs. 5% carbogen produced a response that was significantly stronger (P < 0.05) than air‐only breathing in volunteers. Subjects imaged during the follicular phase of their cycle when estrogen levels typically peak exhibited a significantly smaller BOLD response (P = 0.01). Results in malignant tissue were variable, with three out of five lesions exhibiting a diminished response to the gas stimulus. Conclusion Oxygen vs. 5% carbogen is the most robust stimulus for inducing BOLD contrast, consistent with the opposing vasomotor effects of these two gases. Measurements may be confounded by background physiological fluctuations and menstrual cycle changes. J. Magn. Reson. Imaging 2016;44:335–345. PMID:26898173

  3. Thyroid, Renal, and Breast Carcinomas, Chondrosarcoma, Colon Adenomas, and Ganglioneuroma: A New Cancer Syndrome, FAP, or Just Coincidence

    PubMed Central

    Atta, Ihab Shafek; AlQahtani, Fahd Nasser

    2016-01-01

    We are presenting a case associated with papillary thyroid carcinoma, renal cell carcinoma, invasive mammary carcinoma, chondrosarcoma, benign ganglioneuroma, and numerous colon adenomas. The patient had a family history of colon cancer, kidney and bladder cancers, lung cancer, thyroid cancer, leukemia, and throat and mouth cancers. She was diagnosed with colonic villous adenoma at the age of 41 followed by thyroid, renal, and breast cancers and chondrosarcoma at the ages of 48, 64, 71, and 74, respectively. Additionally, we included a table with the most common familial cancer syndromes with one or more benign or malignant tumors diagnosed in our case, namely, FAP, HNPCC, Cowden, Peutz-Jeghers, renal cancer, tuberous sclerosis, VHL, breast/other, breast/ovarian, Carney, Werner's, Bloom, Li-Fraumeni, xeroderma pigmentosum, ataxia-telangiectasia, osteochondromatosis, retinoblastoma, and MEN2A. PMID:27087812

  4. Thyroid, Renal, and Breast Carcinomas, Chondrosarcoma, Colon Adenomas, and Ganglioneuroma: A New Cancer Syndrome, FAP, or Just Coincidence.

    PubMed

    Atta, Ihab Shafek; AlQahtani, Fahd Nasser

    2016-01-01

    We are presenting a case associated with papillary thyroid carcinoma, renal cell carcinoma, invasive mammary carcinoma, chondrosarcoma, benign ganglioneuroma, and numerous colon adenomas. The patient had a family history of colon cancer, kidney and bladder cancers, lung cancer, thyroid cancer, leukemia, and throat and mouth cancers. She was diagnosed with colonic villous adenoma at the age of 41 followed by thyroid, renal, and breast cancers and chondrosarcoma at the ages of 48, 64, 71, and 74, respectively. Additionally, we included a table with the most common familial cancer syndromes with one or more benign or malignant tumors diagnosed in our case, namely, FAP, HNPCC, Cowden, Peutz-Jeghers, renal cancer, tuberous sclerosis, VHL, breast/other, breast/ovarian, Carney, Werner's, Bloom, Li-Fraumeni, xeroderma pigmentosum, ataxia-telangiectasia, osteochondromatosis, retinoblastoma, and MEN2A. PMID:27087812

  5. Isodeoxyelephantopin from Elephantopus scaber (Didancao) induces cell cycle arrest and caspase-3-mediated apoptosis in breast carcinoma T47D cells and lung carcinoma A549 cells

    PubMed Central

    2014-01-01

    Background Isodeoxyelephantopin (IDOE) isolated from Elephantopus scaber L. (Didancao) is used in Chinese medicine for the treatment of some types of cancer. The anti-cancer mechanism of IDOE remains unclear. This study aims to investigate the antiproliferative activity of IDOE on breast carcinoma T47D cells and lung carcinoma A549 cells. Methods The growth inhibitory effects of IDOE on breast carcinoma T47D cells, lung carcinoma A549 cells, and normal lymphocytes were evaluated by the MTT assay. Morphological analysis of apoptosis induction was performed by acridine orange/ethidium bromide dual-staining and Hoechst 33342 nuclear staining. The cell cycle profile, caspase-3 expression, and annexin V staining were evaluated by flow cytometry. Results IDOE inhibited the growth of A549 and T47D cells in a dose- and time-dependent manner with IC50 values of 10.46 and 1.3 μg/mL, respectively. IDOE was not significantly toxic to normal lymphocytes. The cells became detached from the monolayer and rounded up, had fragmented nuclei and condensed chromatin, and the numbers of apoptotic cells increased (P = 0.0003). IDOE-induced cell death was associated with activated caspase-3 expression followed by cell cycle arrest at G2/M phase. Conclusions IDOE inhibited the proliferation of breast cancer cells and lung carcinoma cells and induced caspase-3-mediated apoptosis and cell cycle arrest in the treated cells. PMID:24742378

  6. Type III Collagen Directs Stromal Organization and Limits Metastasis in a Murine Model of Breast Cancer

    PubMed Central

    Brisson, Becky K.; Mauldin, Elizabeth A.; Lei, Weiwei; Vogel, Laurie K.; Power, Ashley M.; Lo, Albert; Dopkin, Derek; Khanna, Chand; Wells, Rebecca G.; Puré, Ellen; Volk, Susan W.

    2016-01-01

    Breast cancer metastasis is the leading cause of cancer-related deaths in women worldwide. Collagen in the tumor microenvironment plays a crucial role in regulating tumor progression. We have shown that type III collagen (Col3), a component of tumor stroma, regulates myofibroblast differentiation and scar formation after cutaneous injury. During the course of these wound-healing studies, we noted that tumors developed at a higher frequency in Col3+/− mice compared to wild-type littermate controls. We, therefore, examined the effect of Col3 deficiency on tumor behavior, using the murine mammary carcinoma cell line 4T1. Notably, tumor volume and pulmonary metastatic burden after orthotopic injection of 4T1 cells were increased in Col3+/− mice compared to Col3+/+ littermates. By using murine (4T1) and human (MDA-MB-231) breast cancer cells grown in Col3-poor and Col3-enriched microenvironments in vitro, we found that several major events of the metastatic process were suppressed by Col3, including adhesion, invasion, and migration. In addition, Col3 deficiency increased proliferation and decreased apoptosis of 4T1 cells both in vitro and in primary tumors in vivo. Mechanistically, Col3 suppresses the procarcinogenic microenvironment by regulating stromal organization, including density and alignment of fibrillar collagen and myofibroblasts. We propose that Col3 plays an important role in the tumor microenvironment by suppressing metastasis-promoting characteristics of the tumor-associated stroma. PMID:25795282

  7. Veliparib and Pegylated Liposomal Doxorubicin Hydrochloride in Treating Patients With Recurrent Ovarian Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer or Metastatic Breast Cancer

    ClinicalTrials.gov

    2016-07-25

    Estrogen Receptor Negative; HER2/Neu Negative; Male Breast Carcinoma; Progesterone Receptor Negative; Recurrent Breast Carcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Stage IV Breast Cancer; Triple-Negative Breast Carcinoma

  8. Pure Apocrine Carcinomas Represent a Clinicopathologically Distinct Androgen Receptor-Positive Subset of Triple-Negative Breast Cancers.

    PubMed

    Mills, Anne M; E Gottlieb, Chelsea; M Wendroth, Scott; M Brenin, Christiana; Atkins, Kristen A

    2016-08-01

    Apocrine carcinomas comprise ∼1% of all breast cancers and are characterized by large cells bearing abundant eosinophilic granular cytoplasm, round nuclei, and prominent nucleoli. They are typically estrogen receptor/progesterone receptor/HER2 negative, making them unresponsive to typical hormonal or HER2-based chemotherapy. However, this subtype of triple-negative breast cancers expresses androgen receptor (AR), a feature not shared by most nonapocrine triple-negative cancers (NA-TNCs). AR therefore represents a potential diagnostic tool and therapeutic target for apocrine breast carcinoma. All pure apocrine carcinomas diagnosed during a 10-year period were reviewed, and clinicopathologic characteristics were compared with a control group of 26 NA-TNC cases. Twenty apocrine carcinomas were identified (∼0.8% of all breast cancers). The mean age at diagnosis was 69.3 years for apocrine carcinomas and 56.7 years for NA-TNC. All apocrine carcinomas and no NA-TNC were AR positive. The proportions of apocrine carcinoma grades varied, with G1 being seen in 15% of patients, G2 in 55%, and G3 in 30%. In contrast, 100% of NA-TNC cases were G3. The majority of apocrine carcinomas presented at low T stage (T1: 70%; T2: 20%; T3: 10%; T4: 0%), whereas NA-TNC cases more often presented at T2 or higher (T1: 46.2%; T2: 30.8%; T3: 11.5%; T4: 11.5%). Thirty percent of apocrine carcinomas and 30.8% of NA-TNCs had nodal metastases at presentation. Apocrine carcinomas had a favorable clinical prognosis, with 80% of patients showing no evidence of disease-related morbidity or mortality (mean follow-up: 45.2 mo). Pure apocrine carcinomas represent a clinicopathologically distinct subgroup of triple-negative breast cancer characterized by AR positivity. When compared with NA-TNC, apocrine carcinomas more often present in older women with lower grade and T stage, a group in which a more conservative treatment regimen is often desired. PMID:27259012

  9. PD-L1 (B7-H1) expression and the immune tumor microenvironment in primary and metastatic breast carcinomas.

    PubMed

    Cimino-Mathews, Ashley; Thompson, Elizabeth; Taube, Janis M; Ye, Xiaobu; Lu, Yao; Meeker, Alan; Xu, Haiying; Sharma, Rajni; Lecksell, Kristen; Cornish, Toby C; Cuka, Nathan; Argani, Pedram; Emens, Leisha A

    2016-01-01

    Programmed death ligand 1 (PD-L1) expression by tumor-infiltrating lymphocytes (TILs) and tumor cells in breast cancer has been reported, but the relationships between PD-L1 expression by TIL, carcinoma cells, and other immunologic features of the breast tumor microenvironment remain unclear. We therefore evaluated the interrelationships between tumor cell surface and TIL PD-L1 expression, lymphocyte subpopulations, and patterns of immune cell infiltration in cohorts of treatment-naive, primary breast cancers (PBCs) (n = 45) and matched PBC and metastatic breast cancers (MBC) (n = 26). Seventy-eight percent of untreated PBCs contained PD-L1(+) TILs, but only 21% had PD-L1(+) carcinoma cells. Carcinoma PD-L1 expression localized to the tumor invasive front and was associated with high tumor grade (P = .04). Eighty-nine percent of PD-L1(+) carcinomas contained brisk TIL infiltrates, compared to only 24% of PD-L1(-) carcinomas; this included CD3(+) (P = .02), CD4(+) (P = .04), CD8(+) (P = .002), and FoxP3(+) T cells (P = .02). PD-L1(+) PBCs were more likely to contain PD-L1(+) TIL than PD-L1(-) PBCs (P = .04). Peripheral lymphoid aggregates were present in 100% of PD-L1(+) compared to 41% of PD-L1(-) PBC (P < .001). No patient with PD-L1(+) PBC developed distant recurrence, compared to 15% of patients with PD-L1(-) PBC. For the matched PBC and MBC cohort, 2 patients (8%) had PD-L1(+) tumors, with 1 case concordant and 1 case discordant for carcinoma PD-L1 expression in the PBC and MBC. Our data support PD-L1 expression by tumor cells as a biomarker of active breast tumor immunity and programmed death 1 blockade as a therapeutic strategy for breast cancer. PMID:26527522

  10. Evaluation of radioactive phosphorus in the palliation of metastatic bone lesions from carcinoma of the breast and prostate

    SciTech Connect

    Cheung, A.; Driedger, A.A.

    1980-01-01

    Radioactive phosphorus effected substantial palliation of intractable bone pain in 17 of 33 (51.5%) women with metastatic carcinoma of the breast and in 14 of 15 (93.3%) men with metastatic carcinoma of the prostate. No significant difference in the overall response rate was found between androgen and paralthormone priming prior to radiophosphorus therapy. The degree of response was not dependent on total dose of /sup 32/P within the range of 9 to 18 mCi (333 to 666 MPq). Myelosuppression was a transient complication in 9 of 33 patients with metastatic breast carcinoma and in 7 of 15 patients with metastatic prostate carcinoma. Symptomatic hypercalcemia was an infrequent complication of radiophosphorus therapy irrespective of the priming regimen.

  11. A Clinical Pitfall: Optimal Management of Single Dural-based Metastatic Carcinoma of the Breast Mimicking Meningioma.

    PubMed

    Li, Chiao-Zhu; Li, Chiao-Ching; Lin, Meng-Chi; Chih-Chuan, Hsieh; Chen, Nan-Fu; Chen, Chun-Lin; Tang, Chi-Tun

    2015-11-01

    Meningioma is the most common benign brain lesion in adults. Conservative treatment is suggested if there is no obvious neurological symptom or mass effect, but cerebral metastases require aggressive therapy. Single dural-based metastatic carcinoma mimicking meningioma is uncommon. Here is a case of clinical dilemma between meningioma and metastatic carcinoma mimicking meningioma. A woman with a history of invasive ductal carcinoma of the breast presented with headache and blurred vision. Brain computed tomography and magnetic resonance imaging (MRI) both gave the impression of meningioma. After surgical resection of the brain lesion, histopathology revealed that it was a metastatic lesion from the breast. This report discussed the optimal management of single dural-based metastatic carcinoma mimicking meningioma. PMID:26566041

  12. Genomic differences between pure ductal carcinoma in situ and synchronous ductal carcinoma in situ with invasive breast cancer

    PubMed Central

    Kim, Min Sung; Baek, In-Pyo; Lee, Sung Hak; Kim, Tae-Min; Chung, Yeun-Jun; Lee, Sug Hyung

    2015-01-01

    Although ductal carcinoma in situ (DCIS) precedes invasive ductal carcinoma (IDC), the related genomic alterations remain unknown. To identify the genomic landscape of DCIS and better understand the mechanisms behind progression to IDC, we performed whole-exome sequencing and copy number profiling for six cases of pure DCIS and five pairs of synchronous DCIS and IDC. Pure DCIS harbored well-known mutations (e.g., TP53, PIK3CA and AKT1), copy number alterations (CNAs) and chromothripses, but had significantly fewer driver genes and co-occurrence of mutation/CNAs than synchronous DCIS-IDC. We found neither recurrent nor significantly mutated genes with synchronous DCIS-IDC compared to pure DCIS, indicating that there may not be a single determinant for pure DCIS progression to IDC. Of note, synchronous DCIS genomes were closer to IDC than pure DCIS. Among the clinicopathologic parameters, progesterone receptor (PR)-negative status was associated with increased mutations, CNAs, co-occurrence of mutations/CNAs and driver mutations. Our results indicate that although pure DCIS has already acquired some drivers, more changes are needed to progress to IDC. In addition, IDC-associated DCIS is more aggressive than pure DCIS at genomic level and should really be considered IDC. Finally, the data suggest that PR-negativity could be used to predict aggressive breast cancer genotypes. PMID:25831047

  13. Patterns of loss of heterozygosity in breast carcinoma during neoadjuvant chemotherapy.

    PubMed

    Oudin, Claire; Bonnetain, Frank; Boidot, Romain; Végran, Frédérique; Soubeyrand, Marie-Sophie; Arnould, Laurent; Riedinger, Jean-Marc; Lizard-Nacol, Sarab

    2007-05-01

    There is evidence indicating that resistance to some chemotherapy drugs is related to enhanced repair of DNA lesions. Microsatellite instability (MSI) and loss of heterozy-gosity (LOH) reflect genetic instability and are associated with specific DNA repair pathways. Despite the strong implication of genetic instability in breast cancer its association with chemotherapy is unknown. Thus, we analyzed microsatellite alterations with 12 markers in locally advanced breast carcinomas in relation to neoadjuvant epirubicin-cyclophosphamide-containing chemotherapy (FEC-100) and compared it to a docetaxol-based (Tax-Epi) regimen. Samples were obtained before, during and after treatments. In pre-treated samples, MSI was detected only in 2 cases (7%) whereas LOH was found in 23 of the 34 (68%) carcinomas including 10 belonging to the FEC-100 group and 13 to Tax-Epi one. LOH frequency decreased from the first course of both regimens, but differences between the patterns of LOH during treatment were found. Persistent LOH was more frequent in FEC-100 group (71% vs. 41%) that was detected only in biopsies belonging to non-responder patients. Persistent LOH were clustered at particular loci located at regions containing common fragile sites (FHIT and FRA6E). Analysis of baseline LOH with 6 markers located at 3p indicates discontinuous patterns reflecting double-strand break (DSB) lesions. These results agree with a drug-dependent link between genetic instability and chemoresistance and show that FEC-100 treatment is associated with DSB accumulation manifested as LOH in tumor cells resistant to chemotherapy in breast carcinoma. PMID:17390016

  14. Prognostic significance of inflammatory factors expression by stroma from breast carcinomas.

    PubMed

    Fernandez-Garcia, Belen; Eiro, Noemi; Miranda, Maria-Angeles; Cid, Sandra; González, Luis O; Domínguez, Francisco; Vizoso, Francisco J

    2016-08-01

    The aim of this work was to evaluate the expression and clinical relevance of some cytokines in breast carcinomas. An immunohistochemical study using tissue arrays and specific antibodies against interleukin 1β (IL-1β), IL-6, IL-10, IL-17, interferon β (IFNβ) and nuclear factor kappa B (NFκB) was performed in 108 breast carcinomas. Most studied cytokines were mainly expressed by cancer cells but also by stromal cells as cancer-associated fibroblasts (CAFs) or mononuclear inflammatory cells (MICs). Global expression (score) of IL-1β and IL-17 was positively associated with histological grade; human epidermal growth factor receptor 2-positive tumors showed a higher global expression of IFNβ but a lower global expression of NFκB; and node-negative tumors showed a higher global expression of IL-6. High score of IL-6 was significantly associated with both longer relapse free-survival (RFS) and overall survival (OS). Moreover, the expression of IL-1β by each stromal cells (CAFs and MICs) was significantly associated with both longer RFS and OS, whereas the expression of IL-10 by these cells was significantly associated with both shorter RFS and OS. However, the combination of IL-1β, IL-6 and IL-10 expression by MICs reached an important association with prognosis and improved our previously reported prognostic signification based on the matrix metalloprotease 11 status by MICs. The combination of IL-1β, IL-6 and IL-10 expression by MICs was significant and independently associated with distant RFS in a multivariate analysis. Therefore, the combination of the expression of IL-1β, IL-6 and IL-10 may serve as promising biomarkers of MICs with prognostic significance, contributing to a better characterization of breast carcinomas microenvironment. PMID:27207649

  15. Five Year Outcome of 145 Patients With Ductal Carcinoma In Situ (DCIS) After Accelerated Breast Radiotherapy

    SciTech Connect

    Ciervide, Raquel; Dhage, Shubhada; Guth, Amber; Shapiro, Richard L.; Axelrod, Deborah M.; Roses, Daniel F.; Formenti, Silvia C.

    2012-06-01

    Background: Accelerated whole-breast radiotherapy (RT) with tumor bed boost in the treatment of early invasive breast cancer has demonstrated equivalent local control and cosmesis when compared with standard RT. Its efficacy in the treatment of ductal carcinoma in situ (DCIS) remains unknown. Methods and Materials: Patients treated for DCIS with lumpectomy and negative margins were eligible for 2 consecutive hypofractionated whole-breast RT clinical trials. The first trial (New York University [NYU] 01-51) prescribed to the whole breast 42 Gy (2.8 Gy in 15 fractions) and the second trial (NYU 05-181) 40.5 Gy (2.7 Gy in 15 fractions) with an additional daily boost of 0.5 Gy to the surgical cavity. Results: Between 2002 and 2009, 145 DCIS patients accrued, 59 to the first protocol and 86 to the second trial. Median age was 56 years and 65% were postmenopausal at the time of treatment. Based on optimal sparing of normal tissue, 79% of the patients were planned and treated prone and 21% supine. At 5 years' median follow-up (60 months; range 2.6-105.5 months), 6 patients (4.1%) experienced an ipsilateral breast recurrence in all cases of DCIS histology. In 3/6 patients, recurrence occurred at the original site of DCIS and in the remaining 3 cases outside the original tumor bed. New contralateral breast cancers arose in 3 cases (1 DCIS and 2 invasive carcinomas). Cosmetic self-assessment at least 2 years after treatment is available in 125 patients: 91% reported good-to-excellent and 9% reported fair-to-poor outcomes. Conclusions: With a median follow-up of 5 years, the ipsilateral local recurrence rate is 4.1%, comparable to that reported from the NSABP (National Surgical Adjuvant Breast and Bowel Project) trials that employed 50 Gy in 25 fractions of radiotherapy for DCIS. There were no invasive recurrences. These results provide preliminary evidence that accelerated hypofractionated external beam radiotherapy is a viable option for DCIS.

  16. Automatic intraductal breast carcinoma classification using a neural network-based recognition system.

    PubMed

    Reigosa, A; Hernández, L; Torrealba, V; Barrios, V; Montilla, G; Bosnjak, A; Araez, M; Turiaf, M; Leon, A

    1998-07-01

    A contour-based automatic recognition system was applied to classify intraductal breast carcinoma into high nuclear grade and low nuclear grade in a digitized histologic image. The image discriminating characteristics were selected by their invariability condition to rotation and translation. They were acquired from cellular contours information. The totally interconnected multilayer perceptron network architecture was selected, and it was trained with the error back propagation algorithm. Forty cases were analyzed by the system and the diagnoses were compared with that of pathologist consensus, obtaining agreement in 97.5% (p < .00001 of cases). The system may become a very useful tool for the pathologist in the definitive classification of intraductal carcinoma. PMID:21223442

  17. Analysis of serial radionuclide bone images in osteosarcoma and breast carcinoma

    SciTech Connect

    McNeil, B.J.; Hanley, J.

    1980-04-01

    The authors first describe and illustrate didactically the use of the Kaplan-Meier actuarial technique for serial diagnostic studies. They then present an analysis of previously published data on the results of serial radionuclide bone images in patients with osteosarcoma or breast carcinoma, using this technique. The data indicate that patients with osteosarcoma show an almost linear increase in the occurrence of bone metastates between 5 and 29 months after diagnosis; the rate is approximately 1% per month. Patients with breast cancer, on the other hand, show a biphasic rate of development, averaging only 0.5% per month during the first year after diagnosis but increasing rapidly to approximately 2% per month after 15 months.

  18. Neoplastic meningitis from breast carcinoma with complete response to liposomal cytarabine: case report.

    PubMed

    Gaviani, Paola; Silvani, A; Corsini, E; Erbetta, A; Salmaggi, A

    2009-06-01

    Neoplastic meningitis from breast cancer often leads to a progressive neurologic deterioration followed by fatal outcome. The therapy is based on the administration of high dose systemic chemotherapy with drugs able to pass through the blood-brain barrier, such as methotrexate (MTX) and cytarabine, cranial or craniospinal irradiation, and intrathecal (IT) administration of MTX and/or cytarabine. However, these approaches only have modest efficacy and are associated with side effects for the patients. A depot formulation of liposomal cytarabine (DepoCyte) has proven to be useful in clinical trials. We describe the case of a woman with a diagnosis of leptomeningeal carcinomatosis from breast carcinoma who presented cerebrospinal fluid normalization and prolonged complete MRI response to intrathecal chemotherapy with liposomal cytarabine (DepoCyte). PMID:19259616

  19. 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

  20. Magnetic resonance imaging shrinkage patterns following neoadjuvant chemotherapy for breast carcinomas with an emphasis on the radiopathological correlations

    PubMed Central

    TOMIDA, KAORI; ISHIDA, MITSUAKI; UMEDA, TOMOKO; SAKAI, SACHIKO; KAWAI, YUKI; MORI, TSUYOSHI; KUBOTA, YOSHIHIRO; MEKATA, EIJI; NAKA, SHIGEYUKI; ABE, HAJIME; OKABE, HIDETOSHI; TANI, TOHRU

    2014-01-01

    Preoperative neoadjuvant chemotherapy (NAC) is considered to be the standard treatment for locally-advanced breast carcinomas. Obtaining precise information regarding the tumor extent and distribution by imaging modalities to assess the success of breast-conserving surgery following NAC is extremely important. Analysis of the detailed radiopathological correlation of magnetic resonance imaging (MRI) following NAC has not been reported previously. The MRI and histopathological shrinkage patterns of residual breast carcinomas in 27 consecutive cases were analyzed following NAC and classified into five categories: Types I and II (concentric shrinkage with and without surrounding lesions, respectively); type III (shrinkage with residual multinodular lesions); type IV (diffuse contrast enhancement in whole quadrant); and non-visualization. The present study clearly demonstrated that the most common MRI shrinkage pattern was type I (11 cases), followed by type II and non-visualization, and the most common histopathological shrinkage pattern was type II (11 cases), followed by type III (8 cases). The concordance rate between MRI and pathological patterns was 48% and the worst concordance MRI pattern was type I. MRI is considered to be a useful method for evaluation of the residual carcinoma following NAC. However, the concordance rate was low in the MRI pattern I cases and tiny foci of residual carcinoma were present in half of the non-visualization cases, as shown by MRI. Therefore, the tumor extent must be completely resected for patients who undergo NAC, and postoperative radiation may be important for preventing local recurrence of breast carcinoma. PMID:25054046

  1. An Introspective Update on the Influence of miRNAs in Breast Carcinoma and Neuroblastoma Chemoresistance

    PubMed Central

    2014-01-01

    Chemoresistance to conventional cytotoxic drugs may occur in any type of cancer and this can either be inherent or develop through time. Studies have linked this acquired resistance to the abnormal expression of microRNAs (miRNAs) that normally silence genes. At abnormal levels, miRNAs can either gain ability to silence tumour suppressor genes or else lose ability to silence oncogenes. miRNAs can also affect pathways that are involved in drug metabolism, such as drug efflux pumps, resulting in a resistant phenotype. The scope of this review is to provide an introspective analysis on the specific niches of breast carcinoma and neuroblastoma research. PMID:25548681

  2. Invasive breast carcinoma cells from patients exhibit MenaINV- and macrophage-dependent transendothelial migration.

    PubMed

    Pignatelli, Jeanine; Goswami, Sumanta; Jones, Joan G; Rohan, Thomas E; Pieri, Evan; Chen, Xiaoming; Adler, Esther; Cox, Dianne; Maleki, Sara; Bresnick, Anne; Gertler, Frank B; Condeelis, John S; Oktay, Maja H

    2014-11-25

    Metastasis is a complex, multistep process of cancer progression that has few treatment options. A critical event is the invasion of cancer cells into blood vessels (intravasation), through which cancer cells disseminate to distant organs. Breast cancer cells with increased abundance of Mena [an epidermal growth factor (EGF)-responsive cell migration protein] are present with macrophages at sites of intravasation, called TMEM sites (for tumor microenvironment of metastasis), in patient tumor samples. Furthermore, the density of these intravasation sites correlates with metastatic risk in patients. We found that intravasation of breast cancer cells may be prevented by blocking the signaling between cancer cells and macrophages. We obtained invasive breast ductal carcinoma cells of various subtypes by fine-needle aspiration (FNA) biopsies from patients and found that, in an in vitro transendothelial migration assay, cells that migrated through a layer of human endothelial cells were enriched for the transcript encoding Mena(INV), an invasive isoform of Mena. This enhanced transendothelial migration required macrophages and occurred with all of the breast cancer subtypes. Using mouse macrophages and the human cancer cells from the FNAs, we identified paracrine and autocrine activation of colony-stimulating factor-1 receptor (CSF-1R). The paracrine or autocrine nature of the signal depended on the breast cancer cell subtype. Knocking down Mena(INV) or adding an antibody that blocks CSF-1R function prevented transendothelial migration. Our findings indicate that Mena(INV) and TMEM frequency are correlated prognostic markers and CSF-1 and Mena(INV) may be therapeutic targets to prevent metastasis of multiple breast cancer subtypes. PMID:25429076

  3. Expression of leukemia/lymphoma-related factor (LRF/POKEMON) in human breast carcinoma and other cancers.

    PubMed

    Aggarwal, Anshu; Hunter, William J; Aggarwal, Himanshu; Silva, Edibaldo D; Davey, Mary S; Murphy, Richard F; Agrawal, Devendra K

    2010-10-01

    The POK family of proteins plays an important role in not only embryonic development and cell differentiation, but also in oncogenesis. Leukemia/lymphoma-related factor (LRF) belongs to the POK family of transcriptional repressors and is also known as POK erythroid myeloid ontogenic factor (POKEMON), which binds to short transcripts of HIV-1 (FBI-1) and TTF-1 interacting peptide (TIP21). Its oncogenic role is known only in lymphoma, non-small cell lung carcinoma, and malignant gliomas. The functional expression of LRF in human breast carcinoma has not yet been confirmed. The aim of this study was to investigate and compare the expression of LRF in human breast cancer tissues and other human tumors. The expression of LRF mRNA transcripts and protein was observed in twenty human benign and malignant breast biopsy tissues. Expression of LRF was observed in several formalin-fixed tissues by immunohistochemistry and immunofluorescence. All malignant breast tissues expressed mRNA transcripts and protein for LRF. However, 40% and 15% benign breast biopsy tissues expressed LRF mRNA transcripts and protein, respectively. The overall expression of LRF mRNA transcripts and total protein was significantly more in malignant breast tissues than the benign breast tissues. LRF expression was also observed in the nuclei of human colon, renal, lung, hepatocellular carcinomas and thymoma tumor cells. In general, a significantly higher expression of LRF was seen in malignant tissues than in the corresponding benign or normal tissue. Further studies are warranted to determine the malignant role of LRF in human breast carcinoma. PMID:20471975

  4. Muscular pseudotumor of the breast following doxorubicin and radiation therapy for oat cell carcinoma of the lung

    SciTech Connect

    Wergowske, G.; Chang, J.C.; Marger, D.

    1982-12-01

    Two male patients developed muscular pseudotumor of the breast following combined treatment of radiation and chemotherapy with cyclophosphamide, doxorubicin, methotrexate and procarbazine for oat cell carcinoma of the lung. The pathologic findings of the biopsy specimens revealed muscle and capillary changes similar to previously reported myocardiotoxicity from doxorubicin and radiation therapy. Discussed is a possible additive or synergistic toxic effect of doxorubicin and radiation therapy in the development of muscular pseudotumor of the breast.

  5. Experimental evaluation of boron neutron capture therapy of human breast carcinoma implanted on nude mice

    NASA Astrophysics Data System (ADS)

    Bose, Satya Ranjan

    2000-06-01

    An in-pool small animal irradiation neutron tube (SAINT) facility was designed, constructed and installed at the University of Virginia Nuclear Research Reactor (UVAR). Thermal neutron flux profiles were measured by foil activation analysis (gold) and verified with DORT and MCNP computer code models. The gamma-ray absorbed dose in the neutron-gamma mixed field was determined from TLD measurements. The SAINT thermal neutron flux was used to investigate the well characterized human breast cancer cell line MCF-7B on both in-vitro samples and in- vivo animal subjects. Boronophenylalanine (BPA enriched in 95% 10B) was used as a neutron capturing agent. The in-vitro response of MCF-7B human breast carcinoma cells to BPA in a mixed field of neutron-gamma radiation or pure 60Co gamma radiation was investigated. The best result (lowest surviving fraction) was observed in cell cultures pre-incubated with BPA and given the neutron irradiation. The least effective treatment consisted of 60Co irradiation only. Immunologically deficient nude mice were inoculated subcutaneously with human breast cancer MCF-7B cells and estradiol pellets (to support tumor growth). The tumor volume in the mouse control group increased over time, as expected. The group of mice exposed only to neutron treatment exhibited initial tumor volume reduction lasting until 35 days following the treatment, followed by renewed tumor growth. Both groups given BPA plus neutron treatment showed continuous reduction in tumor volume over the 55-day observation period. The group given the higher BPA concentration showed the best tumor reduction response. The results on both in-vitro and in-vivo studies showed increased cell killing with BPA, substantiating the incorporation of BPA into the tumor or cell line. Therefore, BNCT may be a possible choice for the treatment of human breast carcinoma. However, prior to the initiation of any clinical studies, it is necessary to determine the therapeutic efficacy in a large

  6. In vivo study of breast carcinoma radiosensitization by targeting eIF4E

    SciTech Connect

    Yang, Hua; Li, Li-Wen; Shi, Mei; Wang, Jian-Hua; Xiao, Feng; Zhou, Bin; Diao, Li-Qiong; Long, Xiao-Li; Liu, Xiao-Li; Xu, Lin

    2012-07-13

    Highlights: Black-Right-Pointing-Pointer eIF4E is associated with the formation and progression for breast cancer. Black-Right-Pointing-Pointer pSecX-t4EBP1 can downregulated the expression of eIF4E in direct binding. Black-Right-Pointing-Pointer We transfected pSecX-t4EBP1 into a mouse xenograft model. Black-Right-Pointing-Pointer It can significantly inhibit tumor growth and enhance the radiosensitivity. Black-Right-Pointing-Pointer The possible mechanism is downregulation of HIF-1{alpha} expression. -- Abstract: Background: Eukaryotic initiation factor eIF4E, an important regulator of translation, plays a crucial role in the malignant transformation, progression and radioresistance of many human solid tumors. The overexpression of this gene has been associated with tumor formation in a wide range of human malignancies, including breast cancer. In the present study, we attempted to explore the use of eIF4E as a therapeutic target to enhance radiosensitivity for breast carcinomas in a xenograft BALB/C mice model. Materials and methods: Ninety female BALB/C mice transfected with EMT-6 cells were randomly divided into six groups: control, irradiation (IR), pSecX-t4EBP1, pSecX-t4EBP1 + irradiation, pSecX and pSecX + irradiation. At the end of the experiments, all mice were sacrificed, the xenografts were harvested to measure the tumor volume and mass, and the tumor inhibition rates were calculated. Apoptosis was detected with a flow cytometric assay. Immunohistochemistry was used to detect the expression of HIF-1{alpha}. Results: The xenografts in pSecX-t4EBP1 mice showed a significantly delayed growth and smaller tumor volume, with a higher tumor inhibition rate compared with the control and pSecX groups. A similar result was obtained in the pSecX-t4EBP1 + IR group compared with IR alone and pSecX + irradiation. The expression of HIF-1{alpha} in the tumor cells was significantly decreased, while the apoptosis index was much higher. Conclusions: pSecX-t4EBP1 can

  7. Difference in characteristics and outcomes between medullary breast carcinoma and invasive ductal carcinoma: a population based study from SEER 18 database

    PubMed Central

    Li, Jun-Jing; Song, Chuan-Gui; Shao, Zhi-Ming

    2016-01-01

    Medullary breast carcinoma (MBC) is a unique histological subtype of breast cancer. Our study was designed to identify difference in characteristics and outcomes between MBC and invasive ductal carcinoma (IDC), and further confirm the prognostic factors of MBC. Utilizing Surveillance, Epidemiology, and End Results (SEER), we identified 84,764 eligible patients, including 309 MBC and 84,455 IDC. Compared with the IDC group, the MBC group was associated with younger age at diagnosis, higher grade, more advanced stage, larger tumor size, and higher proportion of triple-negative breast cancer (TNBC). Kaplan-Meier analysis and univariate Cox proportional hazard regression model showed that patients with IDC had significantly better breast cancer-specific survival (BCSS) compared to MBC, but they had similar overall survival (OS). However, MBC histology was no longer a surrogate for worse BCSS or OS after 1:1 matching by age, American Joint Committee on Cancer (AJCC) stage, grade and breast subtype. In addition, it was exposed that not married status, high grade, large tumor size, positive nodal status, the subtype of TNBC and no receipt of radiation therapy were significantly associated with poor BCSS and OS. In conclusion, MBC demonstrated more aggressive behavior but similar outcomes compared to IDC, which may be determined by prognostic factors such as breast subtype. These results not only confer deeper insight into MBC but contribute to individualized and tailored therapy, and thereby may improve clinical management and outcomes. PMID:27009810

  8. 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 ...

  9. ADAM33 gene silencing by promoter hypermethylation as a molecular marker in breast invasive lobular carcinoma

    PubMed Central

    2009-01-01

    Background ADAM33 protein is a member of the family of transmembrane glycoproteins composed of multidomains. ADAM family members have different activities, such as proteolysis and adhesion, making them good candidates to mediate the extracellular matrix remodelling and changes in cellular adhesion that characterise certain pathologies and cancer development. It was reported that one family member, ADAM23, is down-regulated by promoter hypermethylation. This seems to correlate with tumour progression and metastasis in breast cancer. In this study, we explored the involvement of ADAM33, another ADAM family member, in breast cancer. Methods First, we analysed ADAM33 expression in breast tumour cell lines by RT-PCR and western blotting. We also used 5-aza-2'-deoxycytidine (5azadCR) treatment and DNA bisulphite sequencing to study the promoter methylation of ADAM33 in breast tumour cell lines. We evaluated ADAM33 methylation in primary tumour samples by methylation specific PCR (MSP). Finally, ADAM33 promoter hypermethylation was correlated with clinicopathological data using the chi-square test and Fisher's exact test. Results The expression analysis of ADAM33 in breast tumour cell lines by RT-PCR revealed gene silencing in 65% of tumour cell lines. The corresponding lack of ADAM33 protein was confirmed by western blotting. We also used 5-aza-2'-deoxycytidine (5-aza-dCR) demethylation and bisulphite sequencing methodologies to confirm that gene silencing is due to ADAM33 promoter hypermethylation. Using MSP, we detected ADAM33 promoter hypermethylation in 40% of primary breast tumour samples. The correlation between methylation pattern and patient's clinicopathological data was not significantly associated with histological grade; tumour stage (TNM); tumour size; ER, PR or ERBB2 status; lymph node status; metastasis or recurrence. Methylation frequency in invasive lobular carcinoma (ILC) was 76.2% compared with 25.5% in invasive ductal carcinoma (IDC), and this

  10. Integrative network-based approach identifies key genetic elements in breast invasive carcinoma

    PubMed Central

    2015-01-01

    Background Breast cancer is a genetically heterogeneous type of cancer that belongs to the most prevalent types with a high mortality rate. Treatment and prognosis of breast cancer would profit largely from a correct classification and identification of genetic key drivers and major determinants driving the tumorigenesis process. In the light of the availability of tumor genomic and epigenomic data from different sources and experiments, new integrative approaches are needed to boost the probability of identifying such genetic key drivers. We present here an integrative network-based approach that is able to associate regulatory network interactions with the development of breast carcinoma by integrating information from gene expression, DNA methylation, miRNA expression, and somatic mutation datasets. Results Our results showed strong association between regulatory elements from different data sources in terms of the mutual regulatory influence and genomic proximity. By analyzing different types of regulatory interactions, TF-gene, miRNA-mRNA, and proximity analysis of somatic variants, we identified 106 genes, 68 miRNAs, and 9 mutations that are candidate drivers of oncogenic processes in breast cancer. Moreover, we unraveled regulatory interactions among these key drivers and the other elements in the breast cancer network. Intriguingly, about one third of the identified driver genes are targeted by known anti-cancer drugs and the majority of the identified key miRNAs are implicated in cancerogenesis of multiple organs. Also, the identified driver mutations likely cause damaging effects on protein functions. The constructed gene network and the identified key drivers were compared to well-established network-based methods. Conclusion The integrated molecular analysis enabled by the presented network-based approach substantially expands our knowledge base of prospective genomic drivers of genes, miRNAs, and mutations. For a good part of the identified key drivers

  11. Bilateral inflammatory metachronic ERBB2 (HER2/neu)-positive breast carcinoma: prolonged survival with combined chemotherapy and trastuzumab.

    PubMed

    Lázaro, Alicia; Casinello, Javier; Amorós, Almudena; Heredia, Miriam; López-Alfonso, Ana

    2008-09-01

    A patient with inflammatory breast carcinoma (IBC) diagnosed in the left breast responded to cisplatin and was treated with radical mastectomy and adjuvant therapy. Two years later C-erbB2-positive IBC was diagnosed in the right breast, and was treated with mastectomy and radiotherapy. Two years later skin metastases appeared, and trastuzumab was started initially as monotherapy, and later with paclitaxel and capecitabine. More than 12 years after diagnosis and 7 years after trastuzumab was started, the patient remains in complete clinical remission on trastuzumab and capecitabine. PMID:18796377

  12. Correlation of histopathologic features of ductal carcinoma in situ of the breast with the oncotype DX DCIS score.

    PubMed

    Knopfelmacher, Adriana; Fox, Jana; Lo, Yungtai; Shapiro, Nella; Fineberg, Susan

    2015-09-01

    The Oncotype DX Breast Cancer Assay for ductal carcinoma in situ is used to determine local recurrence risk in patients with ductal carcinoma in situ. The results help select patients with low-risk ductal carcinoma in situ who could forgo radiation therapy after conservative surgery. The genes assessed include five proliferation genes, progesterone receptor (PR), and GSTM-1. Our objective was to determine if PR, mitotic counting, or any other pathologic feature of ductal carcinoma in situ could predict the Oncotype DX DCIS Score. We identified 46 cases of ductal carcinoma in situ with a Oncotype DX DCIS Score. In addition to information obtained from routine pathology, we counted mitotic figures in the ductal carcinoma in situ and noted presence of dense chronic inflammatory infiltrate surrounding ductal carcinoma in situ. We found that PR ≥ 90% (P = 0.004), mitotic count ≤ 1 (P = 0.045), estrogen receptor ≥ 90% (P = 0.046), and low nuclear grade (P < 0.0001) were associated with a low score. Dense chronic inflammation surrounding ductal carcinoma in situ was associated with a high score (P = 0.034).All 13 cases with PR ≥ 90%, ≤ 1 mitotic figure and absence of dense chronic inflammation around ductal carcinoma in situ had a low score (100% specificity). A low score was not observed in any case with at least two of the following--negative PR, >1 mitotic figure, and/or presence of dense chronic inflammation around ductal carcinoma in situ (100% specificity). Our study suggests using a combination of PR (≥ 90% vs negative) with mitotic count in ductal carcinoma in situ (≤ 1 vs >1) and dense chronic inflammation around ductal carcinoma in situ one could predict the Oncotype DX DCIS score. Mitotic counting and evaluation of immune response might provide prognostic information in ductal carcinoma in situ. PMID:26111975

  13. Predicting discordant HER2 results in ipsilateral synchronous invasive breast carcinomas: experience from a single institution.

    PubMed

    Chou, Shaun; Khan, Tayyaba; Mahajan, Hema; Pathmanathan, Nirmala

    2015-12-01

    With the emergence of multiple lines of highly effective Human Epidermal Growth Factor Receptor 2 (HER2) directed therapy, accurate identification of HER2 positive tumour has become a critical aspect in the histopathological analysis of breast cancers. Multifocal invasive breast carcinomas are relatively common, and given the aggressive inherent biology of HER2 positive disease, identification of even small tumours with HER2 positive status may be of importance for treatment planning. There are currently no clear guidelines as to whether all of these foci should be tested for HER2 status. We reviewed the results of 172 patients in whom HER2 in situ hybridisation (ISH) testing was performed on at least two ipsilateral synchronous invasive carcinomas. Discordant results in different invasive foci were relatively uncommon and occurred in only eight (5%) of the 172 patients. This showed a statistically significant correlation with similarly discordant oestrogen receptor (ER) results. In addition HER2 discordance was more likely amongst different tumour foci if these arose in distinct and separate areas of DCIS. An algorithm based on a combination of College of American Pathologists (CAP) recommendation for HER2 testing, differing ER status and background DCIS profile may be useful in detecting these discordant cases. PMID:26517643

  14. Ductal carcinoma in situ of the breast: the importance of morphologic and molecular interactions.

    PubMed

    Mardekian, Stacey K; Bombonati, Alessandro; Palazzo, Juan P

    2016-03-01

    Ductal carcinoma in situ (DCIS) of the breast is a lesion characterized by significant heterogeneity, in terms of morphology, immunohistochemical staining, molecular signatures, and clinical expression. For some patients, surgical excision provides adequate treatment, but a subset of patients will experience recurrence of DCIS or progression to invasive ductal carcinoma (IDC). Recent years have seen extensive research aimed at identifying the molecular events that characterize the transition from normal epithelium to DCIS and IDC. Tumor epithelial cells, myoepithelial cells, and stromal cells undergo alterations in gene expression, which are most important in the early stages of breast carcinogenesis. Epigenetic modifications, such as DNA methylation, together with microRNA alterations, play a major role in these genetic events. In addition, tumor proliferation and invasion is facilitated by the lesional microenvironment, which includes stromal fibroblasts and macrophages that secrete growth factors and angiogenesis-promoting substances. Characterization of DCIS on a molecular level may better account for the heterogeneity of these lesions and how this manifests as differences in patient outcome and response to therapy. Molecular assays originally developed for assessing likelihood of recurrence in IDC are recently being applied to DCIS, with promising results. In the future, the classification of DCIS will likely incorporate molecular findings along with histologic and immunohistochemical features, allowing for personalized prognostic information and therapeutic options for patients with DCIS. This review summarizes current data regarding the molecular characterization of DCIS and discusses the potential clinical relevance. PMID:26826418

  15. Thrombospondin 1 expression and angiogenesis in breast carcinoma and their relation with platelet activity

    PubMed Central

    Ersoz, Gulriz; Dilek, Fatma Husniye; Gencer, Ercan; Kosar, Mehmet Nuri; Dilek, Osman Nuri

    2009-01-01

    This study investigates angiogenesis and the expression of thrombospondin 1 in invasive ductal carcinoma of the breast and their possible relation to platelet counts and platelet activity. The study included 20 cases of invasive ductal carcinoma. Platelet activity was evaluated by determining thromboxane B2 and cyclic guanosine monophosphate (cGMP) levels by enzyme immunoassay (EIA).Thrombospondin (TSP) 1 and CD34 expression was studied immunohistochemically. Mean platelet count of the patient group was significantly greater than the mean platelet count of the control group (P < 0.05). The platelet counts were positively correlated with tumour size (r=0.609; P < 0.01). Platelet counts were higher in the patients who had grade 3 microvessel density (P < 0.05). The mean basal platelet cGMP level in the patient group was significantly lower than it was in the control group (P < 0.05). Focal TSP immunoreactivity was detectable in 5 (20%) cases in the tumour cells, and in 9 (45%) cases in the stroma. We did not find any correlation between TSP-1 staining and angiogenesis, platelet counts, platelet activity, and the histological prognostic parameters. Our study confirms the essential role of platelets in tumour growth and angiogenesis. Decreased levels of cGMP in the patient group may cause platelet hyperreactivity. Although thrombospondin 1 may be upregulated in malignant breast tissue, this is not sufficient for tumour growth and dissemination according to our results. PMID:19396698

  16. Exemestane With or Without Entinostat in Treating Patients With Recurrent Hormone Receptor-Positive Breast Cancer That is Locally Advanced or Metastatic

    ClinicalTrials.gov

    2016-09-15

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

  17. Lysyl oxidase-like 2 (LOXL2), a new regulator of cell polarity required for metastatic dissemination of basal-like breast carcinomas

    PubMed Central

    Moreno-Bueno, Gema; Salvador, Fernando; Martín, Alberto; Floristán, Alfredo; Cuevas, Eva P; Santos, Vanesa; Montes, Amalia; Morales, Saleta; Castilla, Maria Angeles; Rojo-Sebastián, Alejandro; Martínez, Alejandra; Hardisson, David; Csiszar, Katalin; Portillo, Francisco; Peinado, Héctor; Palacios, José; Cano, Amparo

    2011-01-01

    Basal-like breast carcinoma is characterized by the expression of basal/myoepithelial markers, undifferentiated phenotype, highly aggressive behaviour and frequent triple negative status (ESR−, PR−, Her2neu−). We have previously shown that epithelial–mesenchymal transition (EMT) occurs in basal-like breast tumours and identified Lysyl-oxidase-like 2 (LOXL2) as an EMT player and poor prognosis marker in squamous cell carcinomas. We now show that LOXL2 mRNA is overexpressed in basal-like human breast carcinomas. Breast carcinoma cell lines with basal-like phenotype show a specific cytoplasmic/perinuclear LOXL2 expression, and this subcellular distribution is significantly associated with distant metastatic incidence in basal-like breast carcinomas. LOXL2 silencing in basal-like carcinoma cells induces a mesenchymal-epithelial transition (MET) associated with a decrease of tumourigenicity and suppression of metastatic potential. Mechanistic studies indicate that LOXL2 maintains the mesenchymal phenotype of basal-like carcinoma cells by a novel mechanism involving transcriptional downregulation of Lgl2 and claudin1 and disorganization of cell polarity and tight junction complexes. Therefore, intracellular LOXL2 is a new candidate marker of basal-like carcinomas and a target to block metastatic dissemination of this aggressive breast tumour subtype. PMID:21732535

  18. Rates of Second Malignancies After Definitive Local Treatment for Ductal Carcinoma In Situ of the Breast

    SciTech Connect

    Shaitelman, Simona F.; Grills, Inga S.; Kestin, Larry L.; Ye Hong; Nandalur, Sirisha; Huang Jiayi; Vicini, Frank A.

    2011-12-01

    Purpose: We analyzed the risk of second malignancies developing in patients with ductal carcinoma in situ (DCIS) undergoing surgery and radiotherapy (S+RT) vs. surgery alone. Methods and Materials: The S+RT cohort consisted of 256 women treated with breast-conserving therapy at William Beaumont Hospital. The surgery alone cohort consisted of 2,788 women with DCIS in the regional Surveillance, Epidemiology, and End Results database treated during the same time period. A matched-pair analysis was performed in which each S+RT patient was randomly matched with 8 surgery alone patients (total of 2,048 patients). Matching criteria included age {+-} 2 years. The rates of second malignancies were analyzed overall and as contralateral breast vs. non-breast cancers and by organ system. Results: Median follow-up was 13.7 years for the S+RT cohort and 13.3 years for the surgery alone cohort. The overall 10-/15-year rates of second malignancies among the S+RT and surgery alone cohorts were 14.2%/24.2% and 16.4%/22.6%, respectively (p = 0.668). The 15-year second contralateral breast cancer rate was 14.2% in the S+RT cohort and 10.3% in the surgery alone cohort (p = 0.439). The 15-year risk of a second non-breast malignancy was 14.2% for the S+RT cohort and 13.4% for the surgery alone cohort (p = 0.660). When analyzed by organ system, the 10- and 15-year rates of second malignancies did not differ between the S+RT and surgery alone cohorts for pulmonary, gastrointestinal, central nervous system, gynecologic, genitourinary, lymphoid, sarcomatoid, head and neck, or unknown primary tumors. Conclusions: Compared with surgery alone, S+RT is not associated with an overall increased risk of second malignancies in women with DCIS.

  19. Effect of Metformin on Breast Ductal Carcinoma In Situ Proliferation in a Randomized Presurgical Trial.

    PubMed

    DeCensi, Andrea; Puntoni, Matteo; Guerrieri-Gonzaga, Aliana; Cazzaniga, Massimiliano; Serrano, Davide; Lazzeroni, Matteo; Vingiani, Andrea; Gentilini, Oreste; Petrera, Marilena; Viale, Giuseppe; Cuzick, Jack; Bonanni, Bernardo; Pruneri, Giancarlo

    2015-10-01

    Metformin is associated with lower breast cancer risk in epidemiologic studies and showed decreased proliferation in HER2-positive breast cancer in a presurgical trial. To provide insight into its preventive potential, we measured proliferation by Ki-67 labeling index (LI) of intraepithelial lesions surrounding breast cancer. We randomly assigned 200 nondiabetic patients diagnosed with invasive breast cancer in core biopsies to metformin, 1,700 mg or placebo once daily for 28 days before surgery. Upon surgery, five to seven specimens of cancer adjacent (≤1 cm) and distant (>1 cm) tissue were screened for LCIS, ductal carcinoma in situ (DCIS), and ductal hyperplasia (DH). The prevalence of LCIS, DCIS, and DH was 4.5% (9/200), 67% (133/200), and 35% (69/200), respectively. Overall, metformin did not affect Ki-67 LI in premalignant disorders. The median posttreatment Ki-67 LI (IQR) in the metformin and placebo arm was, respectively, 15% (5-15) versus 5% (4-6) in LCIS (P = 0.1), 12% (8-20) versus 10% (7-24) in DCIS (P = 0.9), and 3% (1-4) versus 3% (1-4) in DH (P = 0.5). However, posttreatment Ki-67 in HER2-positive DCIS lesions was significantly lower in women randomized to metformin especially when ER was coexpressed: 22% (11-32) versus 35% (30-40) in HER2-positive DCIS (n = 22, P = .06); 12% (7-18) versus 32% (27-42) in ER-positive/HER2-positive DCIS (n = 15, P = .004). Eight of 22 (36%) HER2-positive DCIS were adjacent to HER2-negative invasive breast cancer. In tissue samples obtained following 4 weeks of study drug, proliferation was lower in HER2-positive DCIS for women randomized to metformin versus placebo. An adjuvant trial incorporating metformin in HER2-positive DCIS is warranted. PMID:26276754

  20. Lipid-rich carcinoma of the breast that is strongly positive for estrogen receptor: a case report and literature review.

    PubMed

    Oba, Takaaki; Ono, Mayu; Iesato, Asumi; Hanamura, Toru; Watanabe, Takayuki; Ito, Tokiko; Kanai, Toshiharu; Maeno, Kazuma; Ito, Ken-Ichi; Tateishi, Ayako; Yoshizawa, Akihiko; Takayama, Fumiyoshi

    2016-01-01

    Lipid-rich carcinoma (LRC) of the breast is a rare breast cancer variant that accounts for <1% of all breast malignancies. It has been reported that LRCs are negative for estrogen receptor. Here, we report a case of LRC of the breast that was strongly positive for estrogen receptor and treated with endocrine adjuvant therapy. A 52-year-old postmenopausal female noticed a lump in her right breast by self-examination and presented to our hospital. Physical examination revealed an elastic 30 mm ×20 mm hard mass in the upper medial part of her right breast. The findings obtained using ultrasonography, mammography, and contrast-enhanced magnetic resonance imaging suggested breast cancer. Core needle biopsy resulted in the diagnosis of invasive carcinoma. The patient underwent mastectomy and sentinel lymph node biopsy. Histopathologically, the tumor cells were abundant in foamy cytoplasm. Because the presence of marked cytoplasmic lipid droplets was confirmed by Sudan IV staining and electron microscopic examination of the tumor and the lipid droplets were negative for periodic acid-Schiff staining, the tumor was diagnosed as an LRC. Immunohistochemically, estrogen and progesterone receptors of the tumor were strongly positive, human epidermal growth factor receptor type 2 was negative, and the ratio of Ki-67-positive cells was ~30%. After surgery, the patient underwent combination chemotherapy with anthracycline, cyclophosphamide, and 5-fluorouracil, followed by docetaxel. Thereafter, the pateint was treated with letrozole and has remained well for 24 months with no signs of recurrence. PMID:27051299

  1. Lipid-rich carcinoma of the breast that is strongly positive for estrogen receptor: a case report and literature review

    PubMed Central

    Oba, Takaaki; Ono, Mayu; Iesato, Asumi; Hanamura, Toru; Watanabe, Takayuki; Ito, Tokiko; Kanai, Toshiharu; Maeno, Kazuma; Ito, Ken-ichi; Tateishi, Ayako; Yoshizawa, Akihiko; Takayama, Fumiyoshi

    2016-01-01

    Lipid-rich carcinoma (LRC) of the breast is a rare breast cancer variant that accounts for <1% of all breast malignancies. It has been reported that LRCs are negative for estrogen receptor. Here, we report a case of LRC of the breast that was strongly positive for estrogen receptor and treated with endocrine adjuvant therapy. A 52-year-old postmenopausal female noticed a lump in her right breast by self-examination and presented to our hospital. Physical examination revealed an elastic 30 mm ×20 mm hard mass in the upper medial part of her right breast. The findings obtained using ultrasonography, mammography, and contrast-enhanced magnetic resonance imaging suggested breast cancer. Core needle biopsy resulted in the diagnosis of invasive carcinoma. The patient underwent mastectomy and sentinel lymph node biopsy. Histopathologically, the tumor cells were abundant in foamy cytoplasm. Because the presence of marked cytoplasmic lipid droplets was confirmed by Sudan IV staining and electron microscopic examination of the tumor and the lipid droplets were negative for periodic acid–Schiff staining, the tumor was diagnosed as an LRC. Immunohistochemically, estrogen and progesterone receptors of the tumor were strongly positive, human epidermal growth factor receptor type 2 was negative, and the ratio of Ki-67-positive cells was ~30%. After surgery, the patient underwent combination chemotherapy with anthracycline, cyclophosphamide, and 5-fluorouracil, followed by docetaxel. Thereafter, the pateint was treated with letrozole and has remained well for 24 months with no signs of recurrence. PMID:27051299

  2. Solid Variant of Adenoid Cystic Carcinoma of the Breast: A Case Series With Proposal of a New Grading System.

    PubMed

    Foschini, Maria P; Rizzo, Antonio; De Leo, Antonio; Laurino, Licia; Sironi, Maria; Rucco, Vittorio

    2016-04-01

    Adenoid cystic carcinoma (ACC) of the breast is a low-grade malignancy "triple negative" breast tumor. ACC of the breast can present a great variety of morphological features having a prognostic impact. Recently, cases of ACC having solid-basaloid features (SBACC) have been described. In the present study, 6 cases of SBACC have been reported. All the cases affected female patients aged 47 to 69 years (mean = 54 years). Two patients had metastases to the axillary lymph nodes, and 2 patients experienced local recurrences. No deaths due to the tumor were observed. A review of the literature on breast SBACC showed that local recurrences and lymph node metastases are more frequent than in the ACC conventional type; nevertheless, no deaths due to the tumor are registered at the moment. On the contrary, cases of ACC with features of malignant transformation are on record. Therefore, a new grading system on breast ACC is proposed. PMID:26378056

  3. Irradiation with external beam and interstitial radioactive implant as primary treatment for early carcinoma of the breast

    SciTech Connect

    Martinez, A.; Goffinet, D.

    1981-03-01

    The locoregional control of 60 to 61 patients supports the results published by other centers and compares favorably with results of any surgical series. The cosmetic results are excellent with only three of 61 patients having severe fibrosis of the breast develop. No rib fractures, skin ulcerations, symptomatic radiation pneumonitis, edema of the arm or limitation of arm movement have been observed as complications. Ten of the 28 patients who have had axillary dissection had transient edema of the breast develop. Results of numerous studies suggest that primary radiotherapy without mastectomy is appropriate treatment for early carcinoma of the breast. The accessibility of the breast makes it relatively easy to deliver curative doses of radiation with minimal damage to surrounding normal tissues. The cumulative radiotherapy experience has demonstrated the gratifying results of not only maintaining a rather normal breast but also avoiding the negative physical and psychologic repercussions of the mastectomy. Radiation therapy is an alternative to Halsted's radical mastectomy.

  4. Adenomyoepithelioma of the breast coexisting with ductal carcinoma in situ: a case report and review of the literature.

    PubMed

    Kamei, Mirei; Daa, Tsutomu; Miyawaki, Michiyo; Suehiro, Shuji; Sugio, Kenji

    2015-12-01

    We herein report a case of adenomyoepithelioma (AME) of the breast with ductal carcinoma in situ (DCIS) involving a 71-year-old Japanese woman. She presented with bloody discharge from the left nipple. Mammography and ultrasonography showed a well-defined polygonal tumor. Fine-needle aspiration cytology of the mass and stamp cytology of the bloody nipple discharge showed malignancy. Mastectomy and a sentinel lymph node biopsy were performed. The final diagnosis was AME of the breast with DCIS. There are no reports of AME of the breast presenting with bloody nipple discharge; upon a diagnosis of AME of the breast with bloody nipple discharge, the possibility of the coexistence of breast cancer should thus be considered when encountering such cases. PMID:26380805

  5. Enhancement of fibroblast activation protein α-based vaccines and adenovirus boost immunity by cyclophosphamide through inhibiting IL-10 expression in 4T1 tumor bearing mice.

    PubMed

    Xia, Qiu; Geng, Fei; Zhang, Fang-Fang; Liu, Chen-Lu; Xu, Ping; Lu, Zhen-Zhen; Zhang, Hai-Hong; Kong, Wei; Yu, Xiang-Hui

    2016-08-31

    Fibroblast activation protein α (FAPα) is expressed in cancer-associated fibroblasts (CAFs) of more than 90% of malignant epithelia carcinomas. CAFs are the main type of cells in the tumor microenvironment which offer nutrition and protection to the tumor and regulate immunosuppression. To eliminate CAFs, a vaccine targeting FAPα may be used with a heterologous prime-boost strategy to enhance the FAPα-specific cellular immunity. Here, a FAP vaccine using a recombinant adenovirus (rAd) vector was constructed as well as a DNA vaccine reported in our previous work. Although the DNA prime-rAd boost strategy enhanced FAPα-specific immune responses, improvement of anti-tumor immunity effects was not observed. Examination of immunosuppressive factors revealed that high expression of the IL-10 cytokine was considered the main cause of the failure of the prime-boost strategy. However, heterologous vaccination in combination with a low-dose of cyclophosphamide (CY), which was reported to reduce IL-10 production and promote a shift from immunosuppression to immunopotentiation, resulted in enhanced effects in terms of numbers of effector T cells and tumor growth inhibition rates, compared to the CY alone or DNA alone group. Tumor growth was inhibited markedly when the prime-boost strategy was combined with CY in both the prophylactic and therapeutic settings and the survival time of 4T1 tumor bearing mice was also prolonged significantly. With the reduction of IL-10, enhancement of the anti-tumor effect by the prime-boost strategy was observed. These results suggest that FAPα-targeted rAd boosting in combination with CY is an attractive approach to overcoming immunosuppression in cancer vaccines. PMID:27498213

  6. Monoclonal antibody BrE-3 participation in a multivariate prognostic model for infiltrating ductal carcinoma of the breast.

    PubMed

    Chan, C M; Baratta, F S; Ozzello, L; Ceriani, R L

    1994-01-01

    Monoclonal antibody (MoAb) BrE-3, an anti-human milk fat globule (HMFG) MoAb, is used here as a novel prognostic indicator for survival and relapse time in patients with infiltrating ductal carcinoma of the breast. A scoring system (4-Score method) was developed to this effect that measured, in a statistically reliable fashion, the level of expression of the epitope for MoAb BrE-3 in the cytoplasm and membranes of breast carcinoma cells in paraffin-embedded sections. In univariate analysis, data obtained by the 4-Score Method as well as data from traditional prognostic indicators (tumor size, axillary node status, and grade of differentiation) were found to be associated with patient survival and relapse. In multivariate analysis, using a Cox proportional hazards regression model, levels of expression of BrE-3 epitope plus tumor size and axillary node status were weighted and combined in an Individual Linear Composite Prognostic Score (ILCPS) that had a high level of association with survival and relapse time in this sample model of patients with infiltrating ductal carcinoma of the breast. This level of association was found to be higher than the level of association for any other combination of traditional or 4-Score method variables. The level of expression of BrE-3 significantly adds to the prognostic capacity of traditional prognostic markers for infiltrating ductal carcinoma of the breast. PMID:7981443

  7. Metastatic ductal carcinoma of the breast to the thyroid gland diagnosed with fine needle aspiration: A case report with emphasis on morphologic and immunophenotypic features.

    PubMed

    Magers, Martin J; Dueber, Julie C; Lew, Madelyn; Pang, Judy C; Davenport, Robertson D

    2016-06-01

    Metastases to the thyroid are uncommon [<0.2% of thyroid fine needle aspirations (FNA)]. Of metastases to the thyroid, breast carcinoma is relatively common. The diagnosis of metastasis to the thyroid has important therapeutic and prognostic implications. To our knowledge, a morphologic and immunophenotypic comparison of metastatic ductal carcinoma of the breast and primary thyroid carcinomas has not been reported. Here, we report the case of a 37-year-old female with a history of metastatic ductal carcinoma of the breast (modified Bloom-Richardson grade 2; ER+, PgR+, HER2+) diagnosed 6 years prior. She developed hoarseness, prompting a CT scan. Multiple thyroid nodules were found, including a 1.5 cm hypoechoic, solid, irregularly-shaped nodule. On FNA, cells were arranged singly and in crowded groups, varied in size and degree of pleomorphism, and exhibited rare nuclear grooves, inconspicuous nucleoli, and rare intracytoplasmic lumina with no nuclear pseudoinclusions or colloid (Figs. 1A and B). These findings raised the differential of papillary thyroid carcinoma (Fig. 1C), follicular neoplasm (Fig. 1D), medullary carcinoma (Fig. 1E), parathyroid (Fig. 1F), and metastatic breast carcinoma. Immunostaining for GATA-3 (+), ER (+), PAX-8 (-), and TTF-1 (-) was consistent with metastatic breast carcinoma (Fig. 2). We conclude that metastatic breast carcinoma to the thyroid may morphologically mimic primary thyroid carcinoma on FNA; a panel of immunomarkers, such as GATA-3, hormonal marker(s), PAX-8, and TTF-1, may be useful in some cases. GATA-3 immunostaining for metastatic breast carcinoma was helpful in our case and has not been previously reported in a thyroid metastasis sampled by FNA. Diagn. Cytopathol. 2016;44:530-534. © 2016 Wiley Periodicals, Inc. PMID:26932153

  8. The relationship between histologic grades of invasive carcinoma of breast ducts and mast cell infiltration

    PubMed Central

    Fakhrjou, Ashraf; Naghavi-Behzad, Mohammad; Montazeri, Vahid; Karkon-Shayan, Farid; Norouzi-Panahi, Leila; Piri, Reza

    2016-01-01

    Introduction: Breast carcinoma is the most prevalent tumors among women. Transformation of inflated cells in immune response leads to increase in inflammatory cells such as macrophages, mast cells (MC) and fibroblasts. The aim of this study was to determine the relationship between grades of invasive carcinoma of the breast ducts and MC infiltration around tumoral cells. Methods: During the present study, 75 female patients suffering from invasive ductal carcinoma who underwent surgery or diagnostic biopsy during 2010 and 2013 in Educational-Medical centers of Tabriz University of Medical Sciences, were included in the study. Based on Bloom-Richardson grading system, 25 cases were selected from each grade. To better observe of MCs, samples were stained by Toluidine blue and MCs were counted in 10 40 × 10 fields. Results: The mean age was 47.56 ± 10.84 and the number of MCs was between 6 and 96 and their overall average was 43.01. Average count of MCs in grade 1, 2 and 3 were 15.92 ± 10.07, 45.32 ± 10.47, and 67.8 ± 20.70, respectively. There was a significant relationship between the number of MCs and increase in disease grade (P < 0.001). With increasing grade of malignancy, the number of MCs had grown. No significant relationship was observed between age and grade of disease or age and number of MC. Conclusion: According to obtained results, number of MC around tumoral cells increased significantly with an increase in the grade of disease. In order to treat in the first stages of the disease, recognizing primary changes in the stroma of cells could be helpful. PMID:27169108

  9. Cytotoxicity of fucosterol containing fraction of marine algae against breast and colon carcinoma cell line

    PubMed Central

    Khanavi, Mahnaz; Gheidarloo, Razieh; Sadati, Nargess; Ardekani, Mohammad Reza Shams; Nabavi, Seyed Mohammad Bagher; Tavajohi, Shohreh; Ostad, Seyed Nasser

    2012-01-01

    Context: Marine algae produce different secondary metabolites with a wide range of biological activities. Many studies have been achieved on the screening of biological effects of marine organisms and a lot of active compounds were isolated and characterized. Aims: In an attempt to find cytotoxic compound of hexane fraction, isolation, identification, and cytotoxicity of active compound of this fraction were performed. Materials and Methods: In this study, total methanolic (70%) extract and partition fractions of hexane, chloroform (CHCl3), ethyl acetate (EtOAc), and MeOH–H2O of Sargassum angustifolium, Chondria dasyphylla, and Ulva flexuosa, collected from coastlines of the Persian Gulf in south of Iran, were studied against colon carcinoma (HT-29), colorectal adenocarcinoma (Caco-2), breast ductal carcinoma (T47D), and Swiss mouse embryo fibroblast (NIH 3T3) cell lines by MTT assay. Statistical Analysis Used: IC50 (median growth inhibitory concentration) values were calculated by Sigmaplot (10) software. Results: Hexane fraction of Chondria dasyphylla (IC50 82.26 ± 4.09 μg/ml) and MeOH-H2O fraction of Ulva flexuosa (IC50 116.92 ± 8.58 μg/ml) showed cytotoxic activity against proliferation of T47D cells. Hexane fraction of Sargassum angustifolium was also observed for cytotoxicity against T47D and HT-29 cell lines (IC50 166.42 ± 26.7 and 190.24 ± 52.8 μg/ml), respectively. An investigation of a component from the hexane fraction of Sargassum angustifolium yielded a steroidal metabolite, fucosterol, with cytotoxicity in T47D and HT29 (IC50 27.94 ± 9.3 and 70.41 ± 7.5 μg/ml). Conclusions: These results indicated that fucosterol, the most abundant phytosterol in brown algae, is responsible for cytotoxic effect of this extract against breast and colon carcinoma cell lines. PMID:22438665

  10. Methylation status and overexpression of COX-2 in Tunisian patients with ductal invasive breast carcinoma.

    PubMed

    Karray-Chouayekh, Sondes; Trifa, Fatma; Khabir, Abdelmajid; Boujelbene, Noureddine; Sellami-Boudawara, Tahia; Daoud, Jamel; Frikha, Mounir; Gargouri, Ali; Mokdad-Gargouri, Raja

    2011-06-01

    Inflammation and hormonal signalling induce the cyclooxygenase-2 (COX-2) expression in solid tumours including breast cancer, which in turn affects cell proliferation, apoptosis and metastasis. The aim of this study was to investigate the expression of COX-2 and its association with clinical parameters, patient's survival, hormones receptors (oestrogen, progesterone), ERBB2 and TP53 expression in 83 cases of infiltrating ductal breast carcinomas. Moreover, the methylation status at the CpG islands of the COX-2 gene promoter was also explored in 70 specimens. We showed that tumours exhibiting moderate to intense COX-2 immunostaining were significantly more frequent in patients over 45 years old (p = 0.027). Moreover, a high level of COX-2 expression correlated with a shorter survival time (p log-rank = 0.04) and was an independent prognostic factor (p = 0.022; HR 6.4; 95% CI = 1.3-31.4). On the other hand, hypermethylation of the COX-2 gene promoter was observed in 27% of cases and strongly associated with smaller tumours (<5 cm, p = 0.011). Furthermore, patients with methylated COX-2 pattern have a better 4-year disease-free survival (p = 0.022) as well as a prolonged overall survival (p log-rank test = 0.034). In conclusion, we showed that high COX-2 expression was associated with reduced survival and was an independent prognostic factor. However, hypermethylation of the COX-2 promoter correlated with a better overall survival in Tunisian patients with breast carcinoma. PMID:21153458

  11. Endometrial evaluation by ultrasonography, hysteroscopy and histopathology in cases of breast carcinoma on Tamoxifen therapy

    PubMed Central

    Jindal, Alka; Mohi, Manjit K.; Kaur, Manjeet; Kaur, Balwinder; Singla, Risham; Singh, Shaunik

    2015-01-01

    Introduction: Tamoxifen, a nonsteroidal antiestrogenic agent, is used widely as adjunctive therapy for women with breast cancer. Most studies have found that the increased relative risk of developing endometrial cancer for women taking Tamoxifen is two to three times higher than that of an age-matched population. So we designed this study to assess the endometrial status in patients taking Tamoxifen for breast carcinoma. Material and Methods: The study was conducted at Govt. Medical College and Rajindra Hospital, Patiala, India. A total of 50 patients of Ca Breast taking Tamoxifen were selected as per study criterion and TVS performed. If endometrial thickness was more than 5 mm hysteroscopy and endometrial HPE was done and data analysed. Results: On ultrasonography 35 patients (70%) had an endometrial thickness up to 5 mm. 15 patients (30%) had an endometrial thickness more than 5mm. Out of these, 11 patients, i.e. 22% of total, had an endometrial thickness of 5.1 to 10 mm and 2 patients, i.e. 4% of total had an endometrial thickness of more than 20 mm. Hysteroscopy was done on 11 patients. Out of these 8 patients had a normal hysteroscopic appearance whereas 3 patients had an abnormal hysteroscopic picture. Endometrial HPE of these 11 patients revealed 2 patients had secretory changes, 1 had polyp change, 1 had atrophic endometrium, 3 had simple endometrial hyperplasia, 1 had endometrial adenocarcinoma and 4 patients were reported to have scanty curetting. Conclusion: The duration of Tamoxifen therapy turned out to have a relationship with the incidence of endometrial carcinoma (P < 0.0001). Also, a relationship was observed between the duration of Tamoxifen therapy and symptom status of the patients (P < 0.0001). This correlation did not extend to duration of Tamoxifen therapy and endometrial thickness. (P = 0.190). This correlation did not extend to duration of Tamoxifen therapy and endometrial thickness. (P = 0.190). PMID:26167055

  12. Chemotherapy: Impact on Anti-Müllerian Hormone Levels in Breast Carcinoma

    PubMed Central

    Seth, Shashi; Dhankhar, Rakesh; Ghalaut, Veena Singh

    2016-01-01

    Introduction Anti-Mullerian Hormone (AMH) is a glycoprotein of the transforming growth factor-β (TGF-β) family that seems to reflect the continuous non-cyclical growth of small follicles and can be considered an indirect index of the size of the resting primordial follicle pool. Accordingly, AMH represents a marker of Ovarian Reserve (OR) and is particularly useful in demonstrating ovarian tissue damage induced by chemotherapy. Aim To evaluate and compare the levels of AMH in Breast Carcinoma patients before and after chemotherapy with age matched healthy controls and to assess whether AMH as a biochemical marker of the OR might improve prediction of chemotherapy related outcomes in these patients. Materials and Methods The present study was conducted in the Department of Biochemistry in collaboration with Department of Radiotherapy, Pt. B.D. Sharma, University of Health Sciences, Rohtak between June 2013 and June 2014. The subjects were divided into two groups. A total of 30 female patients of confirmed diagnosis of breast carcinoma were enrolled in the study group (Group I). The enrolled breast cancer cases were further divided into subgroups (Group-IA=Prechemotherapy & Group-IB= Postchemotherapy). Thirty healthy age matched female volunteers were enrolled as controls (Group II). Serum levels of AMH were determined by the ultrasensitive anti-müllerian hormone/ müllerian inhibiting substance (US AMH/MIS) Enzyme Linked Immuno Sorbent Assay (ELISA). Results There was a significant decrease in serum AMH levels in the both study group-IA and study group-IB as compared to control group-II (p<0.05 and p<0.001 respectively). The prechemotherapy (group-IA) serum AMH levels dropped significantly after chemotherapy (group-IB) (p<0.001). Conclusion AMH levels declined after chemotherapy indicates direct chemotherapy induced damage to the granulosa cells and growing follicles, reflecting decrease ovarian reserve and fertility. PMID:27042447

  13. Development and characterization of a tamoxifen-resistant breast carcinoma xenograft.

    PubMed

    Naundorf, H; Becker, M; Lykkesfeldt, A E; Elbe, B; Neumann, C; Büttner, B; Fichtner, I

    2000-06-01

    A human tamoxifen-resistant mammary carcinoma, MaCa 3366/TAM, originating from a sensitive parental xenograft 3366 was successfully established by treatment of tumour-bearing nude mice with 1-50 mg kg(-1) tamoxifen for 3 years during routine passaging. Both tumours did not differ significantly in OR- and PR-positivity, however, when compared with the sensitive tumour line, the mean OR content of the TAM-resistant subline is slightly lower. An OR-upregulation following withdrawal of oestradiol treatment was observed in the parental tumours but not in the resistant xenografts. Following long-term treatment with tamoxifen, the histological pattern of the breast carcinoma changed. The more differentiated structures being apparent after treatment with 17beta-oestradiol in the original 3366 tumour were not induced in the resistant line. Tamoxifen failed to induce a tumour growth inhibition in comparison to the tamoxifen-sensitive line. The pure anti-oestrogen, ICI 182 780, revealed cross-resistance. Sequence analysis of the hormone-binding domain of the OR of both lines showed no differences, suggesting that either mutations in other regions of the OR are involved in the TAM-resistance phenotype or that mechanisms outside of this protein induced this phenotype. Oestrogen and anti-oestrogen regulate pS2 and cathepsin D expression in 3366 tumours as in the human breast cancer cell line MCF-7. The resistant 3366/TAM tumours have lost this regulation. The established breast cancer xenografts 3366 and 3366/TAM offer the possibility of investigating mechanisms of anti-oestrogen resistance in an in vivo situation. They can be used to test novel approaches to prevent, or to overcome, this resistance in a clinically related manner. PMID:10839300

  14. High SPARC Expression Starting from Dysplasia, Associated with Breast Carcinoma, Is Predictive for Bone Metastasis without Enhancement of Plasma Levels.

    PubMed

    Maroni, Paola; Bendinelli, Paola; Morelli, Daniele; Drago, Lorenzo; Luzzati, Alessandro; Perrucchini, Giuseppe; Bonini, Chiara; Matteucci, Emanuela; Desiderio, Maria Alfonsina

    2015-01-01

    In order to become established in the skeleton, metastatic cells disseminating from the breast carcinoma need to acquire organ-specific traits. There are no effective predictors for who will develop bone metastasis to guide long-term predictive therapy. Our purpose was to individuate events critical for bone colonization to make a molecular classification of breast carcinoma useful for bone-metastasis outcome. In dysplasia adjacent to carcinoma and in pair-matched specimens of bone metastasis we examined SPARC expression and localization as well as Endothelin 1/ETAR signals by immunohistochemistry, and the evaluation of plasma levels of SPARC by ELISA was also performed. In patients with breast carcinoma metastasizing to bone, SPARC and Endothelin 1/ETAR axis were highly expressed from dysplasia until bone metastasis, but the SPARC plasma level was as low as that of normal women, in contrast to patients that never develop bone metastasis, suggesting that circulating SPARC was counter adhesive. Altogether, the early identification of SPARC/Endothelin 1/ETAR in dysplastic lesions would be important to devise therapies preventing metastasis engraftment, since often carcinoma cells spread to distant organs at the time or even before patients present with cancer. PMID:26703564

  15. High SPARC Expression Starting from Dysplasia, Associated with Breast Carcinoma, Is Predictive for Bone Metastasis without Enhancement of Plasma Levels

    PubMed Central

    Maroni, Paola; Bendinelli, Paola; Morelli, Daniele; Drago, Lorenzo; Luzzati, Alessandro; Perrucchini, Giuseppe; Bonini, Chiara; Matteucci, Emanuela; Desiderio, Maria Alfonsina

    2015-01-01

    In order to become established in the skeleton, metastatic cells disseminating from the breast carcinoma need to acquire organ-specific traits. There are no effective predictors for who will develop bone metastasis to guide long-term predictive therapy. Our purpose was to individuate events critical for bone colonization to make a molecular classification of breast carcinoma useful for bone-metastasis outcome. In dysplasia adjacent to carcinoma and in pair-matched specimens of bone metastasis we examined SPARC expression and localization as well as Endothelin 1/ETAR signals by immunohistochemistry, and the evaluation of plasma levels of SPARC by ELISA was also performed. In patients with breast carcinoma metastasizing to bone, SPARC and Endothelin 1/ETAR axis were highly expressed from dysplasia until bone metastasis, but the SPARC plasma level was as low as that of normal women, in contrast to patients that never develop bone metastasis, suggesting that circulating SPARC was counter adhesive. Altogether, the early identification of SPARC/Endothelin 1/ETAR in dysplastic lesions would be important to devise therapies preventing metastasis engraftment, since often carcinoma cells spread to distant organs at the time or even before patients present with cancer. PMID:26703564

  16. HER2 testing in breast carcinoma: very low concordance rate between reference and local laboratories in Brazil.

    PubMed

    Wludarski, Sheila Cristina Lordelo; Lopes, Lisandro Ferreira; Berto E Silva, Tácio R; Carvalho, Filomena M; Weiss, Lawrence M; Bacchi, Carlos E

    2011-03-01

    Breast cancer accounts for approximately one quarter of all cancers in females. HER2 gene amplification or HER2 protein overexpression, detected in about 20% of breast carcinomas, predicts a more aggressive clinical course and determines eligibility for targeted therapy with trastuzumab. HER2 testing has become an essential part of the clinical evaluation of all breast carcinoma patients, and accurate HER2 results are critical in identifying patients who may be benefited from targeted therapy. This study investigated the concordance in the results of HER2 immunohistochemistry assays performed in 500 invasive breast carcinomas between a reference laboratory and 149 local laboratories from all geographic regions of Brazil. Our results showed an overall poor concordance (171 of 500 cases, 34.2%) regarding HER2 results between local and reference laboratories, which may be related to the low-volume load of HER2 assays, inexperience with HER2 scoring system, and/or technical issues related to immunohistochemistry in local laboratories. Standardization of HER2 testing with rigorous quality control measures by local laboratories is highly recommended to avoid erroneous treatment of breast cancer patients. PMID:20930616

  17. Synchronous ovarian dysgerminoma and breast carcinoma in a patient with positive immunostain of BRCA1.

    PubMed

    Băltătescu, G I; Așchie, M; Sârbu, V

    2013-01-01

    Breast cancer is the most common malignant neoplastic process and the second cause of death for women. Ovarian cancer, despite having a lower incidence, represents an important cause of morbidity and mortality because it is usually discovered in advanced stages. The presence of both forms of cancer in a patient is associated with a high risk of BRCA1 gene mutations, which are responsible, together with BRCA2 gene mutations, for most of the breast and ovarian cancer family. Our case is special because it presents a synchronous and a rare association of a primary ovarian dysgerminoma (with an incidence of less than 1% of ovarian cancers) and a primary breast carcinoma in a patient of 46 years old. Immunohistochemical examination was performed using a panel of five biomarkers: oestrogen receptor, progesterone receptor, Herceptest, p53 and BRCA1. In our case, we identified a negative hormonal status and the absence of HER2/neu expression but a positive immuno-expression for p53 protein and BRCA1 protein. Postoperative course was favourable for the patient after each surgery, and she was discharged with the recommendation to perform a genetic counselling. PMID:23618579

  18. White blood cell and platelet indices as prognostic markers in patients with invasive ductal breast carcinoma

    PubMed Central

    Mantas, Dimitrios; Kostakis, Ioannis D.; Machairas, Nikolaos; Markopoulos, Christos

    2016-01-01

    A growing body of evidence suggests that oncogenesis is associated with systemic inflammation. The present study investigated white blood cell and platelet indices, whose values change during the inflammatory response, in women with invasive ductal breast carcinoma. Preoperatively obtained white blood cell and platelet counts from 53 patients with early breast cancer, who developed systemic metastases over a mean follow-up period of 65 months, were analyzed and compared with those of a matching control group formed of 37 patients with the same characteristics, who remained recurrence-free during the same time period. Patients who developed distant metastasis had a significantly higher mean platelet volume and lower neutrophil count than patients who did not present with distant metastasis. Furthermore, time to distant metastasis development was longer in patients with a lower mean platelet volume, whilst patients with a lower neutrophil count had a shorter systemic disease-free time interval. However, receiver operating characteristic curve analysis demonstrated that these parameters provided moderate accuracy in predicting which patients may develop distant metastasis. No differences were detected between patient groups regarding additional parameters. Patients who developed systemic disease during a mean follow-up period of 65 months were observed to have an increased mean platelet volume and decreased neutrophil count preoperatively. These results indicate that such parameters may be of prognostic value in patients with breast cancer. Studies with a larger number of patients are required to further investigate this hypothesis. PMID:27446480

  19. Src, a potential target for overcoming trastuzumab resistance in HER2-positive breast carcinoma

    PubMed Central

    Peiró, G; Ortiz-Martínez, F; Gallardo, A; Pérez-Balaguer, A; Sánchez-Payá, J; Ponce, J J; Tibau, A; López-Vilaro, L; Escuin, D; Adrover, E; Barnadas, A; Lerma, E

    2014-01-01

    Background: Src is a non-receptor tyrosine kinase involved in signalling and crosstalk between growth-promoting pathways. We aim to investigate the relationship of active Src in response to trastuzumab of HER2-positive breast carcinomas. Methods: We selected 278 HER2-positive breast cancer patients with (n=154) and without (n=124) trastuzumab treatment. We performed immunohistochemistry on paraffin-embedded tissue microarrays of active Src and several proteins involved in the PI3K/Akt/mTOR pathway, PIK3CA mutational analysis and in vitro studies (SKBR3 and BT474 cancer cells). The results were correlated with clinicopathological factors and patients' outcome. Results: Increased pSrc-Y416 was demonstrated in trastuzumab-resistant cells and in 37.8% of tumours that correlated positively with tumour size, necrosis, mitosis, metastasis to the central nervous system, p53 overexpression and MAPK activation but inversely with EGFR and p27. Univariate analyses showed an association of increased active Src with shorter survival in patients at early stage with HER2/hormone receptor-negative tumours treated with trastuzumab. Conclusions: Src activation participates in trastuzumab mechanisms of resistance and indicates poor prognosis, mainly in HER2/hormone receptor-negative breast cancer. Therefore, blocking this axis may be beneficial in those patients. PMID:24937674

  20. The Occurrence of Genetic Alterations during the Progression of Breast Carcinoma

    PubMed Central

    Li, Xiao-Chen; Liu, Chenglin; Huang, Tao; Zhong, Yang

    2016-01-01

    The interrelationship among genetic variations between the developing process of carcinoma and the order of occurrence has not been completely understood. Interpreting the mechanisms of copy number variation (CNV) is absolutely necessary for understanding the etiology of genetic disorders. Oncogenetic tree is a special phylogenetic tree inferential pictorial representation of oncogenesis. In our present study, we constructed oncogenetic tree to imitate the occurrence of genetic and cytogenetic alterations in human breast cancer. The oncogenetic tree model was built on CNV of ErbB2, AKT2, KRAS, PIK3CA, PTEN, and CCND1 genes in 963 cases of tumors with sequencing and CNA data of human breast cancer from TCGA. Results from the oncogenetic tree model indicate that ErbB2 copy number variation is the frequent early event of human breast cancer. The oncogenetic tree model based on the phylogenetic tree is a type of mathematical model that may eventually provide a better way to understand the process of oncogenesis. PMID:27190992

  1. Opportunities for Molecular Epidemiological Research on Ductal Carcinoma In-situ and Breast Carcinogenesis: Interdisciplinary Approaches

    PubMed Central

    Sherman, Mark E.; Mies, Carolyn; Gierach, Gretchen L.

    2014-01-01

    Most invasive breast cancers arise from ductal carcinoma in-situ (DCIS), a non-obligate precursor of invasive breast cancer. Given that the natural history of individual DCIS lesions is unpredictable, many women with DCIS receive extensive treatments, which may include surgery, radiation and endocrine therapy, even though many of these lesions may have limited potential to progress to invasion and metastasize. In contrast to valid concerns about over-treatment, the fact that invasive breast cancers outnumber DCIS lesions by more than three-to-one, suggests that many cancer precursors (particularly DCIS, but LCIS also) progress to invasion prior to detection. Thus, DCIS poses a dual problem of over diagnosis among some women and failure of early detection among others. These concerns are heightened by the multi-fold increase in rates of DCIS in conjunction with widespread use of mammographic screening and access to outpatient radiologically-guided biopsies. Accordingly, methods are needed to both specifically detect and identify DCIS lesions with potential to progress to invasive cancer and to discover techniques to triage and conservatively manage indolent cases of DCIS. PMID:24225267

  2. Opportunities for molecular epidemiological research on ductal carcinoma in-situ and breast carcinogenesis: interdisciplinary approaches.

    PubMed

    Sherman, Mark E; Mies, Carolyn; Gierach, Gretchen L

    2014-01-01

    Most invasive breast cancers arise from ductal carcinoma in-situ (DCIS), a non-obligate precursor of invasive breast cancer. Given that the natural history of individual DCIS lesions is unpredictable, many women with DCIS receive extensive treatments, which may include surgery, radiation and endocrine therapy, even though many of these lesions may have limited potential to progress to invasion and metastasize. In contrast to valid concerns about overtreatment, the fact that invasive breast cancers outnumber DCIS lesions by more than three-to-one, suggests that many cancer precursors (particularly DCIS, but LCIS also) progress to invasion prior to detection. Thus, DCIS poses a dual problem of overdiagnosis among some women and failure of early detection among others. These concerns are heightened by the multifold increase in rates of DCIS in conjunction with widespread use of mammographic screening and access to outpatient radiologically-guided biopsies. Accordingly, methods are needed to both specifically detect and identify DCIS lesions with potential to progress to invasive cancer and to discover techniques to triage and conservatively manage indolent cases of DCIS. PMID:24225267

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

    PubMed

    Lesurf, Robert; Aure, Miriam Ragle; Mørk, Hanne Håberg; Vitelli, Valeria; Lundgren, Steinar; Børresen-Dale, Anne-Lise; Kristensen, Vessela; Wärnberg, Fredrik; Hallett, Michael; Sørlie, Therese

    2016-07-26

    Breast cancer consists of at least five main molecular "intrinsic" subtypes that are reflected in both pre-invasive and invasive disease. Although previous studies have suggested that many of the molecular features of invasive breast cancer are established early, it is unclear what mechanisms drive progression and whether the mechanisms of progression are dependent or independent of subtype. We have generated mRNA, miRNA, and DNA copy-number profiles from a total of 59 in situ lesions and 85 invasive tumors in order to comprehensively identify those genes, signaling pathways, processes, and cell types that are involved in breast cancer progression. Our work provides evidence that there are molecular features associated with disease progression that are unique to the intrinsic subtypes. We additionally establish subtype-specific signatures that are able to identify a small proportion of pre-invasive tumors with expression profiles that resemble invasive carcinoma, indicating a higher likelihood of future disease progression. PMID:27396337

  4. Differential diagnosis of lung lesion in breast carcinoma: a metachronous neoplasm or metastasis?

    PubMed

    Maddala, Raja Naga Mahesh; Udupa, Karthik; Thomas, Joseph; Pai, Kanthilatha

    2016-01-01

    A 34-year-old woman-a diagnosed case of pT1N1MO, stage IIa, estrogen and progesterone receptor positive (ER, PR) positive, Her2 negative carcinoma of the left breast-was managed with modified radical mastectomy and adjuvant chemotherapy. While planning for radiotherapy, she was found to have a well-defined enhancing lesion with spiculated margins in the superior segment of the right lower lobe along with a heterogeneously enhancing right hilar lymph node on CT. Histopathological evaluation of the lesion was suggestive of adenocarcinoma. The lesion was negative for ER, PR receptors, mammoglobin and gross cystic disease fluid protein. Thyroid transcription factor 1 (TTF-1) was positive, suggesting a primary lung adenocarcinoma rather than metastatic lesion from the breast. This case clearly signifies the importance of histopathological diagnosis of suspicious metastatic lesions in the setting of early breast cancer. We would also like to highlight the importance of TTF-1 in differentiating primary lung malignancy from metastasis. PMID:27170610

  5. Breast MRI in Invasive Lobular Carcinoma: A Useful Investigation in Surgical Planning?

    PubMed

    Parvaiz, Muhammad Asad; Yang, Peiming; Razia, Eisha; Mascarenhas, Margaret; Deacon, Caroline; Matey, Pilar; Isgar, Brian; Sircar, Tapan

    2016-01-01

    Magnetic resonance imaging (MRI) is highly sensitive in detecting invasive lobular carcinoma (ILC) of the breast. In our institution, patients who are deemed to be suitable for breast conserving surgery (BCS) with unifocal small ILC on standard imaging are offered breast MRI to exclude multifocal and larger ILC. Our study investigates the usefulness of breast MRI in ILC. A prospective cohort study over a 58-month period, including all consecutive patients with ILC having breast MRI. Primary objective was to find out the proportion of ILC patients where preoperative MRI caused a change in the surgical treatment. Secondary objectives included finding mastectomy rate (initial & final), re-operation rate, cancer size correlation with different imaging modalities and final histopathology, loco-regional recurrence and disease-free survival. A total of 334 bilateral breast MRI were performed including 72 (21.5%) MRI for ILC patients. All these MRI were carried out within 2 week of patients given the diagnosis (median 5.5 days). Age range was 24-83 (median 56.5) years. Nineteen of 72 ILC patients (26.4%) had a change in their planned operation from BCS to a different operation owing to MRI findings (seven patients with multifocal cancers, 10 with significantly larger size of the cancer and two with contralateral malignancy). Initial mastectomy rate was 31.9%, final mastectomy rate was 36.1% and re-operation rate in BCS group was 18.3%. MRI correlated better with ILC histopathology cancer size than mammogram and ultrasound scans. There was no statistically significant difference (p = 0.999) between the cancer size on histology (median 23 mm) and MRI (median 25 mm). However, mammogram (median 17 mm) and ultrasound (median 14.5 mm) scans showed cancer sizes significantly different to final histology cancer size (p = 0.0008 and p = 0.0021 respectively). Over a 44 months median follow-up (range 27-85), 95.8% disease-free survival and 98.6% overall survival have been observed

  6. Cytological Study of Breast Carcinoma Before and After Oncotherapy with Special Reference to Morphometry and Proliferative Activity.

    PubMed

    Koley, Sananda; Chakrabarti, Srabani; Pathak, Swapan; Manna, Asim Kumar; Basu, Siddhartha

    2015-12-01

    Our study was done to assess the cytological changes due to oncotherapy in breast carcinoma especially on morphometry and proliferative activity. Cytological aspirates were collected from a total of 32 cases of invasive ductal carcinoma both before and after oncotherapy. Morphometry was done on the stained cytological smears to assess the different morphological parameters of cell dimension by using the ocular morphometer and the software AutoCAD 2007. Staining was done with Ki-67 and proliferating cell nuclear antigen (PCNA) as proliferative markers. Different morphological parameters were compared before and after oncotherapy by unpaired Student's t test. Statistically significant differences were found in morphometric parameters, e.g., mean nuclear diameter, mean nuclear area, mean cell diameter, and mean cell area, and in the expression of proliferative markers (Ki-67 and PCNA). Statistical analysis was done by obtaining p values. There are statistically significant differences between morphological parameter of breast carcinoma cells before and after oncotherapy. PMID:26730066

  7. Next-Generation Sequencing: A powerful tool for the discovery of molecular markers in breast ductal carcinoma in situ

    PubMed Central

    Kaur, Hitchintan; Mao, Shihong; Shah, Seema; Gorski, David H.; Krawetz, Stephen A.; Sloane, Bonnie F.; Mattingly, Raymond R.

    2013-01-01

    Mammographic screening leads to frequent biopsies and concomitant overdiagnosis of breast cancer, particularly ductal carcinoma in situ (DCIS). Some DCIS lesions rapidly progress to invasive carcinoma whereas others remain indolent. Because we cannot yet predict which lesions will not progress, all DCIS is regarded as malignant, and many women are overtreated. Thus, there is a pressing need for a panel of molecular markers in addition to the current clinical and pathologic factors to provide prognostic information. Genomic technologies such as microarrays have made major contributions to defining sub-types of breast cancer. Next-generation sequencing (NGS) modalities offer unprecedented depth of expression analysis through revealing transcriptional boundaries, mutations, rare transcripts and alternative splice variants. NGS approaches are just beginning to be applied to DCIS. Here, we review the applications and challenges of NGS in discovering novel potential therapeutic targets and candidate biomarkers in the premalignant progression of breast cancer. PMID:23477556

  8. Endometrial thickness and risk of breast and endometrial carcinomas in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial

    PubMed Central

    Felix, Ashley S.; Weissfeld, Joel L.; Pfeiffer, Ruth M.; Modugno, Francesmary; Black, Amanda; Hill, Lyndon M.; Martin, Jerry; Sit, Anita S.; Sherman, Mark E.; Brinton, Louise A.

    2013-01-01

    Postmenopausal women with higher circulating estrogen levels are at increased risk of developing breast and endometrial carcinomas. In the endometrium, excess estrogen relative to progesterone produces a net proliferative stimulus, which may result in endometrial thickening. Therefore, we tested the hypothesis that endometrial thickness is a biological marker of excess estrogen stimulation that is associated with risk of breast and endometrial carcinomas. Endometrial thickness was measured in 1,272 postmenopausal women, aged 55–74, who underwent transvaginal ultrasound (TVU) screening as part of the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. Serial endometrial thickness measurements were available for a subset of women at one (n=1,018), two (n=869) and three years (n=641) after baseline. We evaluated associations between endometrial thickness and breast (n=91) and endometrial (n=14) carcinoma by estimating relative risks (RRs) and 95% confidence intervals (CIs) using Cox proportional hazards regression with age as the time metric. Models incorporating baseline endometrial thickness and as a time-varying covariate using all measurements were examined. Median follow-up among study participants was 12.5 years (range: 0.3–13.8 years). Compared to baseline endometrial thickness of 1.0 – 2.99 mm, women with baseline endometrial thickness greater than or equal to 5.0 mm had an increased risk of breast (RR: 2.00, 95% CI 1.15, 3.48) and endometrial (RR: 5.02, 95% CI 0.96, 26.36) carcinomas in models adjusted for menopausal hormone use and BMI. Our data suggest that increased endometrial thickness as assessed by TVU was associated with increased risk of breast and endometrial carcinomas. PMID:23907658

  9. Options for Breast Reconstruction after Mastectomy for Carcinoma of the Breast: An Observational Experience at MSKCC, New York under UICC Fellowship.

    PubMed

    Das, Prafulla Kumar; Cordeiro, Peter G

    2015-12-01

    The first Author went to visit The Memorial Sloan Kettering Cancer Center (MSKCC), New York, USA on UICC ICRETT Fellowship to observe as many clinical situations of options of breast reconstruction after mastectomy for carcinoma breast during a period of 1 month in June 2014. The second Author was the Supervisor for such clinical observation at the Plastic and Reconstructive Service, Department of Surgery at MSKCC. The main objective of this project was to gain a deeper understanding of the various options for reconstruction and specific operative skills and techniques needed for reconstruction after surgical resections for breast carcinoma. The gained experience would benefit our Regional Cancer Center's physicians, patients, and families. All patients treated by the Plastic and Reconstructive Surgery Service, Department of Surgery, Memorial Sloan Kettering Cancer Center (MSKCC) who underwent surgical resection and reconstruction of their breast mounds were observed during the period between June 1, 2014 and June 30, 2014. It was observed that a vast majority of patients who underwent a mastectomy at MSKCC were offered primary breast reconstruction. They underwent thorough counseling and teaching about the various options, and feasibility with regard to their specific case. Patients eventually made the final choice on type of reconstruction, type of implant, and type of nipple/areola reconstruction. A majority of patients underwent implant reconstruction at MSKCC. This was partly related to the high rate of bilateral mastectomies (close to 50 %) as well as a significant rate of post mastectomy radiation (15 to 20 %). PMID:27065656

  10. Diversity of Matriptase Expression Level and Function in Breast Cancer

    PubMed Central

    Welman, Arkadiusz; Sproul, Duncan; Mullen, Peter; Muir, Morwenna; Kinnaird, Andrew R.; Harrison, David J.; Faratian, Dana; Brunton, Valerie G.; Frame, Margaret C.

    2012-01-01

    Overexpression of matriptase has been reported in a variety of human cancers and is sufficient to trigger tumor formation in mice, but the importance of matriptase in breast cancer remains unclear. We analysed matriptase expression in 16 human breast cancer cell lines and in 107 primary breast tumors. The data revealed considerable diversity in the expression level of this protein indicating that the significance of matriptase may vary from case to case. Matriptase protein expression was correlated with HER2 expression and highest expression was seen in HER2-positive cell lines, indicating a potential role in this subgroup. Stable overexpression of matriptase in two breast cancer cell lines had different consequences. In MDA-MB-231 human breast carcinoma cells the only noted consequence of matriptase overexpression was modestly impaired growth in vivo. In contrast, overexpression of matriptase in 4T1 mouse breast carcinoma cells resulted in visible changes in morphology, actin staining and cell to cell contacts. This correlated with downregulation of the cell-cell adhesion molecule E-cadherin. These results suggest that the functions of matriptase in breast cancer are likely to be variable and cell context dependent. PMID:22514623

  11. Breast Cancer Heterogeneity Examined by High-Sensitivity Quantification of PIK3CA, KRAS, HRAS, and BRAF Mutations in Normal Breast and Ductal Carcinomas.

    PubMed

    Myers, Meagan B; Banda, Malathi; McKim, Karen L; Wang, Yiying; Powell, Michael J; Parsons, Barbara L

    2016-04-01

    Mutant cancer subpopulations have the potential to derail durable patient responses to molecularly targeted cancer therapeutics, yet the prevalence and size of such subpopulations are largely unexplored. We employed the sensitive and quantitative Allele-specific Competitive Blocker PCR approach to characterize mutant cancer subpopulations in ductal carcinomas (DCs), examining five specific hotspot point mutations (PIK3CA H1047R, KRAS G12D, KRAS G12V, HRAS G12D, and BRAF V600E). As an approach to aid interpretation of the DC results, the mutations were also quantified in normal breast tissue. Overall, the mutations were prevalent in normal breast and DCs, with 9/9 DCs having measureable levels of at least three of the five mutations. HRAS G12D was significantly increased in DCs as compared to normal breast. The most frequent point mutation reported in DC by DNA sequencing, PIK3CA H1047R, was detected in all normal breast tissue and DC samples and was present at remarkably high levels (mutant fractions of 1.1 × 10(-3) to 4.6 × 10(-2)) in 4/10 normal breast samples. In normal breast tissue samples, PIK3CA mutation levels were positively correlated with age. However, the PIK3CA H1047R mutant fraction distributions for normal breast tissues and DCs were similar. The results suggest PIK3CA H1047R mutant cells have a selective advantage in breast, contribute to breast cancer susceptibility, and drive tumor progression during breast carcinogenesis, even when present as only a subpopulation of tumor cells. PMID:27108388

  12. Breast Cancer Heterogeneity Examined by High-Sensitivity Quantification of PIK3CA, KRAS, HRAS, and BRAF Mutations in Normal Breast and Ductal Carcinomas12

    PubMed Central

    Myers, Meagan B.; Banda, Malathi; McKim, Karen L.; Wang, Yiying; Powell, Michael J.; Parsons, Barbara L.

    2016-01-01

    Mutant cancer subpopulations have the potential to derail durable patient responses to molecularly targeted cancer therapeutics, yet the prevalence and size of such subpopulations are largely unexplored. We employed the sensitive and quantitative Allele-specific Competitive Blocker PCR approach to characterize mutant cancer subpopulations in ductal carcinomas (DCs), examining five specific hotspot point mutations (PIK3CA H1047R, KRAS G12D, KRAS G12V, HRAS G12D, and BRAF V600E). As an approach to aid interpretation of the DC results, the mutations were also quantified in normal breast tissue. Overall, the mutations were prevalent in normal breast and DCs, with 9/9 DCs having measureable levels of at least three of the five mutations. HRAS G12D was significantly increased in DCs as compared to normal breast. The most frequent point mutation reported in DC by DNA sequencing, PIK3CA H1047R, was detected in all normal breast tissue and DC samples and was present at remarkably high levels (mutant fractions of 1.1 × 10− 3 to 4.6 × 10− 2) in 4/10 normal breast samples. In normal breast tissue samples, PIK3CA mutation levels were positively correlated with age. However, the PIK3CA H1047R mutant fraction distributions for normal breast tissues and DCs were similar. The results suggest PIK3CA H1047R mutant cells have a selective advantage in breast, contribute to breast cancer susceptibility, and drive tumor progression during breast carcinogenesis, even when present as only a subpopulation of tumor cells. PMID:27108388

  13. [Cutaneous angiosarcoma arising after radiotherapy treatment of a breast carcinoma. Description of a case and review of the literature].

    PubMed

    Di Tommaso, L; Fabbri, A

    2003-08-01

    Cutaneous angiosarcomas occurring as a complication of radiation therapy for breast cancer are rare. To the best of our knowledge 37 cases have been reported in English literature during the last two decades. We describe a case of angiosarcoma arising in the skin of a breast previously irradiated for breast carcinoma. The patient, a 74-year-old woman, had been treated with conservative surgery and radiotherapy for a pT1N0 infiltrating ductal carcinoma of the left breast in 1993. Nine years later a skin lesion, which was interpreted as a recurrence, arose in the same site. A biopsy obtained from the lesion, and initially considered to be negative for cancer, showed istological features consistent with those of the atypical vascular lesion. Seven months later the same lesion transformed in a 5 x 3 reddish mass which at histological examination was diagnosed as an high grad post-irradiation angiosarcoma of the skin of the breast. Data on previously reported post iradiation angiosarcoma of the breast are reviewed; further consideration on differential diagnosis between those lesions and atypical vascular lesions are presented. PMID:14577204

  14. 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

  15. Conservative surgery followed by radical radiotherapy in the management of stage I carcinoma of the breast

    SciTech Connect

    Baeza, M.R.; Arraztoa, J.; Sole, J.; Rodriguez, R.

    1982-10-01

    Since October 1976, the treatment policy in our Radiotheapy Center for Stage I carcinoma of the breast has been excision of the tumor mass, when it was cosmetically suitable, followed by irradiation to the breast and periphereal lymphatics. Eighty-three patients were admitted between October 1976 and March 1980. They underwent local excision of the tumor and then received 5000 rad in 5 weeks to the breast, supraclavicular, axillary and internal mammary chain lymph nodes. Each field was treated every day. A boost was then given to the scar, bringing the dose up to 6500 rad, calculated at maximum tumor depth, depending upon the size of the tumor prior to surgery. Cosmetic results were quite good, and the local control rate at 54 months is 98%. The survival with no evidence of disease (NED) at 54 months (actuarial) is 83%. Twenty-one out of 83 patients have had complications (25.3%); of these, 28.8% were surgical and the remainder results from radiotherapy after surgery, either from radiotherapy alone or from combination of treatments. Of the total of 21 complications, 18 were mild and 3 were serious.These results compare favorably with the results achieved in the same Hospital with radical surgery as far as local tumor control and survival with no evidence of disease (NED) is concerned. The results also compared with the great majority of surgical series reported in the literature, allowing us to conclude that patients treated with radiation have nothing to lose and much to gain by preserving the breast.

  16. Evaluation of androgen receptor and GATA binding protein 3 as immunohistochemical markers in the diagnosis of metastatic breast carcinoma to the lung.

    PubMed

    Hattori, Yukinori; Yoshida, Akihiko; Yoshida, Masayuki; Takahashi, Masahide; Tsuta, Koji

    2015-06-01

    Differentiating metastatic breast carcinoma in the lungs from primary lung tumors and mesotheliomas is important for determining prognosis and treatment. We evaluated novel breast specific markers, androgen receptor (AR) and GATA binding protein 3 (GATA3) immunohistostaining, for this differential, and compare to other traditional markers. The specimens comprised 33 metastatic breast carcinomas to the lung, 566 primary lung tumors (170 adenocarcinomas, 157 squamous cell carcinomas, 31 pleomorphic carcinomas, 115 large cell neuroendocrine carcinomas, 43 small cell carcinomas, and 49 typical carcinoids) and 42 malignant mesotheliomas. They were analyzed by immunohistochemistry using antibodies to AR, GATA3, estrogen receptor (ER), progesterone receptor (PgR), mammaglobin, gross cystic disease fluid protein-15 (GCDFP-15). Of the metastatic breast carcinomas, immunohistostaining of AR, GATA3, ER, PgR, mammaglobin, GCDFP-15 were positive in 27 cases (81.8%), 24 cases (72.7%), 26 cases (78.8%), 13 cases (39.4%), 12 cases (36.4%), 9 cases (27.3%), respectively. Of primary lung tumors and mesotheliomas, staining of AR, GATA3, ER, PgR, mammaglobin, GCDFP-15 were positive in 18 cases (3%), 3 cases (0.5%), 4 cases (0.7%), 2 cases (0.3%), 0 case (0%), 2 cases (0.3%), respectively. Immunohistochemistry of AR and GATA3 are reliable for differentiating metastatic breast carcinoma from primary lung tumors and mesotheliomas. PMID:25727644

  17. 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

  18. Eliminating "ductal carcinoma in situ" and "lobular carcinoma in situ" (DCIS and LCIS) terminology in clinical breast practice: The cognitive psychology point of view.

    PubMed

    Pravettoni, Gabriella; Yoder, Whitney R; Riva, Silvia; Mazzocco, Ketti; Arnaboldi, Paola; Galimberti, Viviana

    2016-02-01

    There is evidence from the literature that the terms "ductal carcinoma in situ" and "lobular carcinoma in situ" (DCIS and LCIS) should be eliminated in clinical breast cancer practice and replaced with the new "ductal intraepithelial neoplasia" (DIN) and "lobular intraepithelial neoplasia" (LIN) terminology. The main purpose of the present article is to expand on this argument from a cognitive psychology perspective and offer suggestions for further research, emphasizing how the elimination of the term "carcinoma" in "in situ" breast cancer diagnoses has the potential to reduce both patient and health care professional confusion and misperceptions that are often associated with the DCIS and LCIS diagnoses, as well as limit the adverse psychological effects of women receiving a DCIS or LCIS diagnosis. We comment on the recent peer-reviewed literature on the clinical implications and psychological consequences for breast cancer patients receiving a DCIS or LCIS diagnosis and we use a cognitive perspective to offer new insight into the benefits of embracing the new DIN and LIN terminology. Using cognitive psychology and cognitive science in general, as a foundation, further research is advocated in order to yield data in support of changing the terminology and therefore, offer a chance to significantly improve the lives and psychological sequelae of women facing such a diagnosis. Typology: Controversies/Short Commentary. PMID:26614547

  19. The Immunophenotype of Nodular Variant of Medullary Carcinoma of the Breast.

    PubMed

    Reyes, Carolina; Nadji, Mehrdad

    2015-10-01

    The histologic and immunohistochemical profile of typical medullary carcinomas (TMC) of the breast are well established. Among the strict histologic criteria for the diagnosis of TMC is complete circumscription of tumor with pushing borders. Those tumors that do not fulfill all morphologic requirements of TMC are designated as atypical medullary carcinomas (AMC). We herewith describe the histology and immunophenotype of a heretofore undescribed variant of TMC composed of multiple distinctly separate nodules that otherwise meet all other histologic and immunohistochemical phenotypes of TMC. Among 2952 cases of infiltrating mammary carcinomas, 111 (3.8%) met the strict criteria for TMC, including positivity for HLA-DR. Nine of these tumors were composed of multiple separate noncoalescing nodules. Immunohistochemical stains for ER, PR, HER2, and HLA-DR, as well as for p53 and Ki-67 were repeated on these nodular forms. Staining for p63 was used to identify possible intraductal components of these tumors. The age of patients ranged from 34 to 53 years. All 9 patients had negative sentinel lymph nodes. Tumors ranged in the overall size from 2.2 to 3.9 cm and were composed of 3 to 6 distinct nodules ranging in size from 0.2 to 1.1 cm surrounding a larger main tumor nodule. The nodules were composed of syncytial groups of large cells with atypical nuclei and prominent nucleoli. A lymphoplasmacytic infiltrate was present within and around each satellite nodule. Serial sections did not show coalescing of the nodules into a single tumor mass. Similarly, staining for p63 failed to support the possibility of nodules representing intraductal components of main tumor. All tumors were negative for ER, PR, and HER2, but positive for HLA-DR. Eight of 9 tumors were diffusely positive for p53 and all 9 showed a high proliferation index in >70% of tumor cells with Ki-67. We conclude that the nodular variants of medullary carcinomas (nTMC) of the breast are uncommon forms of TMC. They

  20. Clinicopathologic features and treatment of breast metastasis from nasopharyngeal carcinoma: A report of two cases and literature review

    PubMed Central

    XIAO, WEIWEI; HE, ZHENYU; XING, CHAO; ZHEN, WEI; WANG, SHAOXIANG; LIN, HUANXIN

    2015-01-01

    Breast metastasis is a rare pattern of distant metastasis from nasopharyngeal carcinoma (NPC) following curative treatment. The present study reported two patients with breast metastasis from NPC and reviewed four such patients reported in the literature, including the analysis of clinical profiles, pathological diagnoses, treatment strategies and outcomes. The breast is a potential metastatic site for patients with NPC following curative treatment; however, thus far, only metachronous breast metastasis has been reported. Infection with Epstein-Barr virus (EBV) was identified in the breast metastasis sites of the two patients investigated in the current study using in situ hybridization for EBV-encoded small RNAs. Patients with breast metastases from NPC consistently and simultaneously develop metastases in other sites. In addition, the two current patients had poor prognoses. Therefore, chemotherapy was the primary treatment strategy administered. A solitary breast metastasis was identified in the male patient. At the most recent follow-up 10 years subsequent to undergoing a Halsted mastectomy, the patient remained alive, however the patient is now lost to follow-up. This case indicates that patients exhibiting NPC with a solitary breast metastasis may still gain long-term survival by undergoing radical mastectomy; therefore, radical mastectomy should be considered in such patients. PMID:26788190

  1. The Anthelmintic Drug Niclosamide Induces Apoptosis, Impairs Metastasis and Reduces Immunosuppressive Cells in Breast Cancer Model

    PubMed Central

    Yan, Yupeng; Xia, Yong; Song, Xuejiao; Liu, Li; Li, Deliang; Wang, Ningyu; Zhang, Lidan; Zhu, Yongxia; Zeng, Jun; Wei, Yuquan; Yu, Luoting

    2014-01-01

    Breast carcinoma is the most common female cancer with considerable metastatic potential. Discovery of new therapeutic approaches for treatment of metastatic breast cancer is still needed. Here, we reported our finding with niclosamide, an FDA approved anthelmintic drug. The potency of niclosamide on breast cancer was assessed in vitro and in vivo. In this investigation, we found that niclosamide showed a dramatic growth inhibition against breast cancer cell lines and induced apoptosis of 4T1 cells in a dose-dependent manner. Further, Western blot analysis demonstrated the occurrence of its apoptosis was associated with activation of Cleaved caspases-3, down-regulation of Bcl-2, Mcl-1 and Survivin. Moreover, niclosamide blocked breast cancer cells migration and invasion, and the reduction of phosphorylated STAT3Tyr705, phosphorylated FAKTyr925 and phosphorylated SrcTyr416 were also observed. Furthermore, in our animal experiments, intraperitoneal administration of 20 mg/kg/d niclosamide suppressed 4T1 tumor growth without detectable toxicity. Histological and immunohistochemical analyses revealed a decrease in Ki67-positive cells, VEGF-positive cells and microvessel density (MVD) and an increase in Cleaved caspase-3-positive cells upon niclosamide. Notably, niclosamide reduced the number of myeloid-derived suppressor cells (MDSCs) in tumor tissues and blocked formation of pulmonary metastases. Taken together, these results demonstrated that niclosamide may be a promising candidate for breast cancer. PMID:24416452

  2. 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

  3. Frequent methylation of the KLOTHO gene and overexpression of the FGFR4 receptor in invasive ductal carcinoma of the breast.

    PubMed

    Dallol, Ashraf; Buhmeida, Abdelbaset; Merdad, Adnan; Al-Maghrabi, Jaudah; Gari, Mamdooh A; Abu-Elmagd, Muhammad M; Elaimi, Aisha; Assidi, Mourad; Chaudhary, Adeel G; Abuzenadah, Adel M; Nedjadi, Taoufik; Ermiah, Eramah; Alkhayyat, Shadi S; Al-Qahtani, Mohammed H

    2015-12-01

    Invasive ductal carcinoma of the breast is the most common cancer affecting women worldwide. The marked heterogeneity of breast cancer is matched only with the heterogeneity in its associated or causative factors. Breast cancer in Saudi Arabia is apparently an early onset with many of the affected females diagnosed before they reach the age of 50 years. One possible rationale underlying this observation is that consanguinity, which is widely spread in the Saudi community, is causing the accumulation of yet undetermined cancer susceptibility mutations. Another factor could be the accumulation of epigenetic aberrations caused by the shift toward a Western-like lifestyle in the past two decades. In order to shed some light into the molecular mechanisms underlying breast cancer in the Saudi community, we identified KLOTHO (KL) as a tumor-specific methylated gene using genome-wide methylation analysis of primary breast tumors utilizing the MBD-seq approach. KL methylation was frequent as it was detected in 55.3 % of breast cancer cases from Saudi Arabia (n = 179) using MethyLight assay. Furthermore, KL is downregulated in breast tumors with its expression induced following treatment with 5-azacytidine. The involvement of KL in breast cancer led us to investigate its relationship in the context of breast cancer, with one of the protagonists of its function, fibroblast growth factor receptor 4 (FGFR4). Overexpression of FGFR4 in breast cancer is frequent in our cohort and this overexpression is associated with poor overall survival. Interestingly, FGFR4 expression is higher in the absence of KL methylation and lower when KL is methylated and presumably silenced, which is suggestive of an intricate relationship between the two factors. In conclusion, our findings further implicate "metabolic" genes or pathways in breast cancer that are disrupted by epigenetic mechanisms and could provide new avenues for understanding this disease in a new context. PMID:26152288

  4. Determination of oestrogen receptors with monoclonal antibodies in fine needle aspirates of breast carcinoma.

    PubMed Central

    Marrazzo, A.; La Bara, G.; Taormina, P.; Bazan, P.

    1989-01-01

    Fifty patients with operable breast carcinoma underwent fine needle aspiration for cytological examination. The smears were prepared by means of the immunocytochemical method using monoclonal antibodies for the determination of the oestrogen receptors (ER). After surgery the contents of the ER were determined with the traditional biochemical technique. The results of the immunocytochemical method showed 31 positives, two of which disagreed with the biochemical results, 15 negatives and four cases which could not be assessed due to the absence of adequate numbers of cells. The ICA staining for ER was expressed on a semiquantitative basis; there was a significant correlation between this and the values expressed by the biochemical technique, with a coefficient of 0.83, P less than 0.000006. PMID:2930709

  5. 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

  6. Consistency in recognizing microinvasion in breast carcinomas is improved by immunohistochemistry for myoepithelial markers.

    PubMed

    Cserni, G; Wells, C A; Kaya, H; Regitnig, P; Sapino, A; Floris, G; Decker, T; Foschini, M P; van Diest, P J; Grabau, D; Reiner, A; DeGaetano, J; Chmielik, E; Cordoba, A; Andreu, X; Zolota, V; Charafe-Jauffret, E; Ryska, A; Varga, Z; Weingertner, N; Bellocq, J P; Liepniece-Karele, I; Callagy, G; Kulka, J; Bürger, H; Figueiredo, P; Wesseling, J; Amendoeira, I; Faverly, D; Quinn, C M; Bianchi, S

    2016-04-01

    Microinvasion is the smallest morphologically identifiable stage of invasion. Its presence and distinction from in situ carcinoma may have therapeutic implications, and clinical staging also requires the recognition of this phenomenon. Microinvasion is established on the basis of several morphological criteria, which may be difficult and not perfectly reproducible among pathologists. The aim of this study was to assess the consistency of diagnosing microinvasion in the breast on traditional haematoxylin and eosin (HE) stained slides and to evaluate whether immunohistochemistry (IHC) for myoepithelial markers could improve this. Digital images were generated from representative areas of 50 cases stained with HE and IHC for myoepithelial markers. Cases were specifically selected from the spectrum of in situ to microinvasive cancers. Twenty-eight dedicated breast pathologists assessed these cases at different magnifications through a web-based platform in two rounds: first HE only and after a washout period by both HE and IHC. Consistency in the recognition of microinvasion significantly improved with the use of IHC. Concordance rates increased from 0.85 to 0.96, kappa from 0.5 to 0.85, the number of cases with 100 % agreement rose from 9/50 to 25/50 with IHC and the certainty of diagnosis also increased. The use of IHC markedly improves the consistency of identifying microinvasion. This corroborates previous recommendations to use IHC for myoepithelial markers to clarify cases where uncertainty exists about the presence of microinvasion. Microinvasive carcinoma is a rare entity, and seeking a second opinion may avoid overdiagnosis. PMID:26818833

  7. Myoepithelial carcinoma of the breast: a clinicopathological and immunohistochemical study of 15 diagnostically challenging cases.

    PubMed

    Buza, Natalia; Zekry, Nazila; Charpin, Colette; Tavassoli, Fattaneh A

    2010-09-01

    Myoepithelial carcinoma (MEC) is a rare type of breast cancer composed purely of myoepithelial cells. Most often it presents with a spindle cell morphology that can mimic several benign and malignant lesions and may be misdiagnosed by the pathologist. We report 15 cases of MEC, which were sent to our consultation practice: Five of them were initially diagnosed as benign. The patients, all female, ranged from 45 to 86 years in age (mean 69.5) and-with one exception-presented with a breast mass. The tumor size measured between 1 and 4.8 cm (mean 2.6 cm). Microscopically, the tumors had infiltrative growth pattern most frequently with thin anastomosing cords of tumor cells associated with an intimately admixed reactive spindle cell stroma. The neoplastic myoepithelial cells were emanating from the myoepithelial cell layer of entrapped ductules in every case. The nuclei showed mild to moderate pleomorphism, and the mitotic activity ranged from 0 to 9/10 high power field. Immunohistochemical stains for p63, CD10, CK903, and CK5/6 reacted strongly and diffusely with the tumor cells, and mainly the reactive stroma had weak positivity for calponin, S-100, and smooth muscle actin. Estrogen receptor, progesteron receptor, and Her2 immunostains were negative, but strong epidermal growth factor receptor expression was observed. Follow-up was available for seven patients: All of them were alive at last contact; one patient had local recurrence, and one developed pulmonary metastases. MEC is a potentially aggressive malignant neoplasm sharing many features with metaplastic carcinomas. Morphologically, it is often difficult to distinguish it from benign spindle cell proliferations. PMID:20658149

  8. p16 expression correlates with basal-like triple-negative breast carcinoma

    PubMed Central

    Abou-Bakr, Amany A; Eldweny, Hany I

    2013-01-01

    Background: Basal-like breast carcinoma (BLBC) has attracted considerable attention over the past few years. It has been suggested that tumours expressing basal markers have a more aggressive clinical behaviour. However, a molecular basis for this disease remains unclear, and it lacks currently used therapeutic targets. Therefore developing a novel treatment strategy is crucial for improving the prognosis. The aim of this study was to characterise the immunohistochemical (IHC) expression of p16 in patients with BLBC compared with non-BLBC. Materials and methods: Eighty-five cases of grade-3 invasive ductal carcinomas not otherwise specified (IDC-NOS) were analyzed. Immunohistochemical stains for oestrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor type 2 (HER2), cytokeratin (CK) 5/6, epidermal growth factor receptor (EGFR) and p16 were performed. BLBC was defined as ER-, PR-, Her2- and CK5/6+, and/or EGFR+. Results: Twenty cases were categorised as BLBC versus 65 as non-basal. High mitotic count and presence of necrosis were associated with basal-like phenotype. Distant metastasis developed in 40% of cases of BLBC with frequent spread to brain and lung. p16 had significantly higher expression in the basal subgroup (80% versus 50.8%, P = 0.04). Patients with BLBCs were found to have a lower disease-free survival (DFS) rate (60% versus 70.8%, P = 0.03). Conclusion: BLBC typically demonstrates a unique profile. p16 is frequently expressed in breast cancers with basal-like phenotype; this suggests that p16 may play a role in the poor prognosis of this tumour, and it may be used in the development of a targeted therapy that will result in improved patient prognostication and outcome. PMID:23717338

  9. Immunohistochemical determination of HER-2/neu expression in invasive breast carcinoma.

    PubMed

    Vang, R; Cooley, L D; Harrison, W R; Reese, T; Abrams, J

    2000-05-01

    Numerous methods exist for HER-2/neu assessment; however, technical and interpretive standardization is virtually absent. We evaluated 2 commercially available antibodies on routinely fixed paraffin-embedded tissue sections to establish our own guidelines. Thirty-three cases of infiltrating breast carcinoma were evaluated simultaneously with monoclonal and polyclonal antibodies. Only membranous staining, no matter how focal, was considered positive. An additional 32 tumors were studied subsequently using only the polyclonal antibody. Of all carcinomas, 13.0% showed immunohistochemical evidence of HER-2/neu overexpression. High-grade tumors were more often positive. There was no HER-2/neu gene expression in the benign epithelium that generally was present in the tissue section or in any of the well-differentiated tumors tested. The polyclonal antibody proved more sensitive than the monoclonal antibody. While true cytoplasmic staining was present occasionally, it did not create substantial difficulty in interpretation. The polyclonal antibody cost substantially less than the monoclonal antibody. Fluorescence in situ hybridization assay for HER-2/neu gene amplification performed on 32 of 65 cases showed concordant results in 31 cases. The immunohistochemical assay for HER-2/neu gene overexpression, using our methods, is accurate, economic, and easily integrated into the laboratory. PMID:10800399

  10. The Polycomb group protein RING1B is overexpressed in ductal breast carcinoma and is required to sustain FAK steady state levels in breast cancer epithelial cells

    PubMed Central

    Bosch, Almudena; Panoutsopoulou, Konstantina; Corominas, Josep Maria; Gimeno, Ramón; Moreno-Bueno, Gema; Martín-Caballero, Juan; Morales, Saleta; Lobato, Tania; Martínez-Romero, Carles; Farias, Eduardo F.; Mayol, Xavier; Cano, Amparo; Hernández-Muáoz, Inmaculada

    2014-01-01

    In early stages of metastasis malignant cells must acquire phenotypic changes to enhance their migratory behavior and their ability to breach the matrix surrounding tumors and blood vessel walls. Epigenetic regulation of gene expression allows the acquisition of these features that, once tumoral cells have escape from the primary tumor, can be reverted. Here we report that the expression of the Polycomb epigenetic repressor Ring1B is enhanced in tumoral cells that invade the stroma in human ductal breast carcinoma and its expression is coincident with that of Fak in these tumors. Ring1B knockdown in breast cancer cell lines revealed that Ring1B is required to sustain Fak expression in basal conditions as well as in Tgfβ-treated cells. Functionally, endogenous Ring1B is required for cell migration and invasion in vitro and for in vivo invasion of the mammary fat pad by tumoral cells. Finally we identify p63 as a target of Ring1B to regulate Fak expression: Ring1B depletion results in enhanced p63 expression, which in turns represses Fak expression. Importantly, Fak downregulation upon Ring1B depletion is dependent on p63 expression. Our findings provide new insights in the biology of the breast carcinoma and open new avenues for breast cancer prognosis and therapy. PMID:24742605

  11. High-throughput proteomic analysis of human infiltrating ductal carcinoma of the breast.

    PubMed

    Somiari, Richard I; Sullivan, Anthony; Russell, Stephen; Somiari, Stella; Hu, Hai; Jordan, Rick; George, Alisha; Katenhusen, Richard; Buchowiecka, Alicja; Arciero, Cletus; Brzeski, Henry; Hooke, Jeff; Shriver, Craig

    2003-10-01

    Large-scale proteomics will play a critical role in the rapid display, identification and validation of new protein targets, and elucidation of the underlying molecular events that are associated with disease development, progression and severity. However, because the proteome of most organisms are significantly more complex than the genome, the comprehensive analysis of protein expression changes will require an analytical effort beyond the capacity of standard laboratory equipment. We describe the first high-throughput proteomic analysis of human breast infiltrating ductal carcinoma (IDCA) using OCT (optimal cutting temperature) embedded biopsies, two-dimensional difference gel electrophoresis (2-D DIGE) technology and a fully automated spot handling workstation. Total proteins from four breast IDCAs (Stage I, IIA, IIB and IIIA) were individually compared to protein from non-neoplastic tissue obtained from a female donor with no personal or family history of breast cancer. We detected differences in protein abundance that ranged from 14.8% in stage I IDCA versus normal, to 30.6% in stage IIB IDCA versus normal. A total of 524 proteins that showed > or = three-fold difference in abundance between IDCA and normal tissue were picked, processed and identified by mass spectrometry. Out of the proteins picked, approximately 80% were unambiguously assigned identities by matrix-assisted laser desorbtion/ionization-time of flight mass spectrometry or liquid chromatography-tandem mass spectrometry in the first pass. Bioinformatics tools were also used to mine databases to determine if the identified proteins are involved in important pathways and/or interact with other proteins. Gelsolin, vinculin, lumican, alpha-1-antitrypsin, heat shock protein-60, cytokeratin-18, transferrin, enolase-1 and beta-actin, showed differential abundance between IDCA and normal tissue, but the trend was not consistent in all samples. Out of the proteins with database hits, only heat shock

  12. Deciphering Genomic Underpinnings of Quantitative MRI-based Radiomic Phenotypes of Invasive Breast Carcinoma.

    PubMed

    Zhu, Yitan; Li, Hui; Guo, Wentian; Drukker, Karen; Lan, Li; Giger, Maryellen L; Ji, Yuan

    2015-01-01

    Magnetic Resonance Imaging (MRI) has been routinely used for the diagnosis and treatment of breast cancer. However, the relationship between the MRI tumor phenotypes and the underlying genetic mechanisms remains under-explored. We integrated multi-omics molecular data from The Cancer Genome Atlas (TCGA) with MRI data from The Cancer Imaging Archive (TCIA) for 91 breast invasive carcinomas. Quantitative MRI phenotypes of tumors (such as tumor size, shape, margin, and blood flow kinetics) were associated with their corresponding molecular profiles (including DNA mutation, miRNA expression, protein expression, pathway gene expression and copy number variation). We found that transcriptional activities of various genetic pathways were positively associated with tumor size, blurred tumor margin, and irregular tumor shape and that miRNA expressions were associated with the tumor size and enhancement texture, but not with other types of radiomic phenotypes. We provide all the association findings as a resource for the research community (available at http://compgenome.org/Radiogenomics/). These findings pave potential paths for the discovery of genetic mechanisms regulating specific tumor phenotypes and for improving MRI techniques as potential non-invasive approaches to probe the cancer molecular status. PMID:26639025

  13. Invasive ductal breast carcinoma detector that is robust to image magnification in whole digital slides.

    PubMed

    Balazsi, Matthew; Blanco, Paula; Zoroquiain, Pablo; Levine, Martin D; Burnier, Miguel N

    2016-04-01

    Invasive ductal breast carcinomas (IDBCs) are the most frequent and aggressive subtypes of breast cancer, affecting a large number of Canadian women every year. Part of the diagnostic process includes grading the cancerous tissue at the microscopic level according to the Nottingham modification of the Scarff-Bloom-Richardson system. Although reliable, there exists a growing interest in automating the grading process, which will provide consistent care for all patients. This paper presents a solution for automatically detecting regions expressing IDBC in images of microscopic tissue, or whole digital slides. This represents the first stage in a larger solution designed to automatically grade IDBC. The detector first tessellated whole digital slides, and image features were extracted, such as color information, local binary patterns, and histograms of oriented gradients. These were presented to a random forest classifier, which was trained and tested using a database of 66 cases diagnosed with IDBC. When properly tuned, the detector balanced accuracy, F1 score, and Dice's similarity coefficient were 88.7%, 79.5%, and 0.69, respectively. Overall, the results seemed strong enough to integrate our detector into a larger solution equipped with components that analyze the cancerous tissue at higher magnification, automatically producing the histopathological grade. PMID:27226977

  14. Deciphering Genomic Underpinnings of Quantitative MRI-based Radiomic Phenotypes of Invasive Breast Carcinoma

    PubMed Central

    Zhu, Yitan; Li, Hui; Guo, Wentian; Drukker, Karen; Lan, Li; Giger, Maryellen L.; Ji, Yuan

    2015-01-01

    Magnetic Resonance Imaging (MRI) has been routinely used for the diagnosis and treatment of breast cancer. However, the relationship between the MRI tumor phenotypes and the underlying genetic mechanisms remains under-explored. We integrated multi-omics molecular data from The Cancer Genome Atlas (TCGA) with MRI data from The Cancer Imaging Archive (TCIA) for 91 breast invasive carcinomas. Quantitative MRI phenotypes of tumors (such as tumor size, shape, margin, and blood flow kinetics) were associated with their corresponding molecular profiles (including DNA mutation, miRNA expression, protein expression, pathway gene expression and copy number variation). We found that transcriptional activities of various genetic pathways were positively associated with tumor size, blurred tumor margin, and irregular tumor shape and that miRNA expressions were associated with the tumor size and enhancement texture, but not with other types of radiomic phenotypes. We provide all the association findings as a resource for the research community (available at http://compgenome.org/Radiogenomics/). These findings pave potential paths for the discovery of genetic mechanisms regulating specific tumor phenotypes and for improving MRI techniques as potential non-invasive approaches to probe the cancer molecular status. PMID:26639025

  15. In vivo photoacoustic molecular imaging of breast carcinoma with folate receptor-targeted indocyanine green nanoprobes

    NASA Astrophysics Data System (ADS)

    Wang, Huina; Liu, Chengbo; Gong, Xiaojing; Hu, Dehong; Lin, Riqiang; Sheng, Zonghai; Zheng, Cuifang; Yan, Meng; Chen, Jingqin; Cai, Lintao; Song, Liang

    2014-11-01

    As an optical-acoustic hybrid imaging technology, photoacoustic imaging uniquely combines the advantages of rich optical contrast with high ultrasonic resolution in depth, opening up many new possibilities not attainable with conventional pure optical imaging technologies. To perform photoacoustic molecular imaging, optically absorbing exogenous contrast agents are needed to enhance the signals from specifically targeted disease activity. In this work, we designed and developed folate receptor targeted, indocyanine green dye doped poly(d,l-lactide-co-glycolide) lipid nanoparticles (FA-ICG-PLGA-lipid NPs) for molecular photoacoustic imaging of tumor. The fabricated FA-ICG-PLGA-lipid NPs exhibited good aqueous stability, a high folate-receptor targeting efficiency, and remarkable optical absorption in near-infrared wavelengths, providing excellent photoacoustic signals in vitro. Furthermore, after intravenous administration of FA-ICG-PLGA-lipid NPs, mice bearing MCF-7 breast carcinomas showed significantly enhanced photoacoustic signals in vivo in the tumor regions, compared with those using non-targeted ICG-PLGA-lipid NPs. Given the existing wide clinical use of ICG and PLGA, the developed FA-ICG-PLGA-lipid NPs, in conjunction with photoacoustic imaging technology, offer a great potential to be translated into the clinic for non-ionizing molecular imaging of breast cancer in vivo.

  16. PCNA and Ki67 expression in breast carcinoma: correlations with clinical and biological variables.

    PubMed Central

    Leonardi, E.; Girlando, S.; Serio, G.; Mauri, F. A.; Perrone, G.; Scampini, S.; Dalla Palma, P.; Barbareschi, M.

    1992-01-01

    AIMS: To investigate the expression of two cell cycle related antigens (proliferating cell nuclear antigen (PCNA) and Ki67 related antigen) in a series of breast cancers; and the possible correlations between the PCNA and Ki67 labelling indexes (PCNA-LI and Ki67-LI) and their associations with other biological and clinicopathological variables. METHODS: Ninety six ductal and 10 lobular carcinoma specimens were investigated. Samples were fixed in formalin and in Methacarnoy for localisation of PCNA. Ki67 was immunostained on frozen sections. The PCNA-LI and Ki67-LI were evaluated in relation to tumour size, mitotic count, histological grade, nodal state as well as receptor content and altered expression of the p53 gene. RESULTS: PCNA-LI did not correlate with Ki67-LI, nor was it associated with any other variable examined. A high KI67-LI (above the median value of 13.5) was associated with high grade and mitotic count, negative receptor content, and altered expression of the p53 gene, but not with other variables. CONCLUSIONS: The PCNA-LI does not seem to be a substitute for the Ki67-LI in evaluating the growth fraction in breast cancer. Images PMID:1350788

  17. Molecular and functional interactions between AKT and SOX2 in breast carcinoma

    PubMed Central

    Mir, Perihan; Konantz, Martina; Pereboom, Tamara C.; Paczulla, Anna M.; Merz, Britta; Fehm, Tanja; Perner, Sven; Rothfuss, Oliver C.; Kanz, Lothar; Schulze-Osthoff, Klaus; Lengerke, Claudia

    2015-01-01

    The transcription factor SOX2 is a key regulator of pluripotency in embryonic stem cells and plays important roles in early organogenesis. Recently, SOX2 expression was documented in various cancers and suggested as a cancer stem cell (CSC) marker. Here we identify the Ser/Thr-kinase AKT as an upstream regulator of SOX2 protein turnover in breast carcinoma (BC). SOX2 and pAKT are co-expressed and co-regulated in breast CSCs and depletion of either reduces clonogenicity. Ectopic SOX2 expression restores clonogenicity and in vivo tumorigenicity of AKT-inhibited cells, suggesting that SOX2 acts as a functional downstream AKT target. Mechanistically, we show that AKT physically interacts with the SOX2 protein to modulate its subcellular distribution. AKT kinase inhibition results in enhanced cytoplasmic retention of SOX2, presumably via impaired nuclear import, and in successive cytoplasmic proteasomal degradation of the protein. In line, blockade of either nuclear transport or proteasomal degradation rescues SOX2 expression in AKT-inhibited BC cells. Finally, AKT inhibitors efficiently suppress the growth of SOX2-expressing putative cancer stem cells, whereas conventional chemotherapeutics select for this population. Together, our results suggest the AKT/SOX2 molecular axis as a regulator of BC clonogenicity and AKT inhibitors as promising drugs for the treatment of SOX2-positive BC. PMID:26498353

  18. Radiotherapy for a benign cause of cauda equina compression in a known case of breast carcinoma

    PubMed Central

    Bhalla, Neeraj; Husband, David J; Pillay, Robin; Thorp, Nicki

    2013-01-01

    A woman underwent breast conservation surgery and axillary clearance for T1N1M0 breast carcinoma, followed by adjuvant chemotherapy, radiotherapy and hormone therapy. At 3-year follow-up she presented with lumbar back pain and developed bilateral lower limb weakness. MRI spine demonstrated an expansile lesion at L1 causing cauda equina compression. The mass, unusually, was centred on the spinous process; metastases typically involve pedicles. The patient underwent surgical decompression with complete resolution of neurological signs. Histology revealed Masson tumour (intravascular papillary endothelial hyperplasia), a benign vascular lesion. Pain recurrence 9 months later prompted imaging demonstrating recurrent mass. Preoperative embolisation and re-excision was undertaken for recurrent Masson tumour. Recurrence of these lesions is rare and it was felt residual disease was likely. Radiotherapy has been used in isolated cases; therefore, she was treated with adjuvant radiotherapy, the first reported case of radiation in management of extracranial Masson tumour, and remains well 3 years later. PMID:23784763

  19. Two cases of breast carcinoma during pregnancy and review of the literature.

    PubMed

    Pascual, Oihana; Uriarte, Moisés; Agustín, Maria-José; Gimeno, Vicente; Larrodé, Itziar; Abad, Maria-Reyes

    2016-08-01

    Pregnancy-associated breast cancer is the most common solid tumor in pregnancy after cervical carcinoma but still has a low incidence. It has been associated with a poor prognosis; though based on a limited number of retrospective case-control studies, some authors have reported no differences from that of non-pregnant patients. There is no consensus about the treatment; it requires an interdisciplinary approach and it is necessary to balance between the benefit for the mother and risk for the fetus. Each case requires an individual decision taking into account the stage of disease, patient preferences and gestational age. Above chemotherapy, it is only recommended after the first trimester of pregnancy and anthracyclin-based schemes have the higher evidence, but taxanes are also considered as an alternative in patients who do not respond to anthracyclines or its use is contraindicated. For the time being, there is a lack of data, and clinical decisions are based on small retrospective cohorts, case-control studies and case reports. We report two cases of patients being diagnosed with breast cancer while being pregnant and treated with surgery and chemotherapy, including anthracyclines, during the second and third trimester of pregnancy. In both reported cases, childbirth was induced before the 37th week of gestation and only one presented low birth weight with no more complications. The echocardiogram monitorization showed normal cardiac function in mothers and fetus. PMID:26018968

  20. Molecular and functional interactions between AKT and SOX2 in breast carcinoma.

    PubMed

    Schaefer, Thorsten; Wang, Hui; Mir, Perihan; Konantz, Martina; Pereboom, Tamara C; Paczulla, Anna M; Merz, Britta; Fehm, Tanja; Perner, Sven; Rothfuss, Oliver C; Kanz, Lothar; Schulze-Osthoff, Klaus; Lengerke, Claudia

    2015-12-22

    The transcription factor SOX2 is a key regulator of pluripotency in embryonic stem cells and plays important roles in early organogenesis. Recently, SOX2 expression was documented in various cancers and suggested as a cancer stem cell (CSC) marker. Here we identify the Ser/Thr-kinase AKT as an upstream regulator of SOX2 protein turnover in breast carcinoma (BC). SOX2 and pAKT are co-expressed and co-regulated in breast CSCs and depletion of either reduces clonogenicity. Ectopic SOX2 expression restores clonogenicity and in vivo tumorigenicity of AKT-inhibited cells, suggesting that SOX2 acts as a functional downstream AKT target. Mechanistically, we show that AKT physically interacts with the SOX2 protein to modulate its subcellular distribution. AKT kinase inhibition results in enhanced cytoplasmic retention of SOX2, presumably via impaired nuclear import, and in successive cytoplasmic proteasomal degradation of the protein. In line, blockade of either nuclear transport or proteasomal degradation rescues SOX2 expression in AKT-inhibited BC cells. Finally, AKT inhibitors efficiently suppress the growth of SOX2-expressing putative cancer stem cells, whereas conventional chemotherapeutics select for this population. Together, our results suggest the AKT/SOX2 molecular axis as a regulator of BC clonogenicity and AKT inhibitors as promising drugs for the treatment of SOX2-positive BC. PMID:26498353

  1. Management of locally advanced carcinoma of the breast by primary radiation therapy

    SciTech Connect

    Harris, J.R.; Sawicka, J.; Gelman, R.; Hellman, S.

    1983-03-01

    A retrospective review of 137 patients with locally advanced breast cancer, but without distant metastases, who were treated with radical radiation therapy is presented. Ninety percent of patients had an initial complete response to their radiation therapy. The 5 year rates of local tumor control, survival free of distant failure, and overall survival were 54% 28% and 30%, respectively. Multivariate analysis revealed that the following features were associated with improved local tumor control: clinically negative axillary nodes, excisional biopsy, radiation dose greater than 6000 rad, and the use of adjuvant systemic therapy. Improved freedom from distant relapse was seen in patients with small primaries and non-inflammatory carcinoma, as well as clinically negative axillary nodes, excisional biopsy, radiation dose greater than 6000 rad, and the use of adjuvant systemic therapy. The results suggest that adequate levels of radiation therapy can provide local tumor control in a significant proportion of patients with locally advanced breast cancer and that adjuvant systemic therapy is useful in improving both local tumor control and freedom from distant relapse in these patients.

  2. [A recurrent case of lipid-secreting carcinoma of the breast successfully treated with capecitabine].

    PubMed

    Suto, Ryuichiro; Miyamoto, Syungo; Kaneda, Yoshikazu; Zenpo, Nobuya; Kurata, Satoru; Nakayasu, Kiyoshi; Kamei, Toshiaki

    2008-09-01

    We herein report a recurrent case of lipid-secreting carcinoma of the breast which was successfully treated with capecitabine. A 50-year-old female underwent a pectoralis-preserving mastectomy for left breast cancer in December 2002. The clinical staging of the disease was T2N1M0 (stage II B) and ER (-), PgR(-), HER2 (1+). Microscopic examinations revealed solid alveolar proliferation in the majority of the tumor cells, which had an abundant foamy cytoplasm. A variable amount of neutral lipid was also identified in the cytoplasm of the tumor cells by Sudan III staining. After the operation, the patient received two courses of systemic chemotherapy using docetaxel (60 mg/m(2)). In March 2004, she was diagnosed to have a recurrence in the thoracic wall. She received radiotherapy (total 50 Gy radiation), but it proved to be ineffective. In June 2004, treatment using capecitabine (2,400 mg/day) was therefore attempted. Two courses of the treatment resulted in a complete response of the tumor. The above patient has since continued to show a complete response with capecitabine for over 3.5 years. PMID:18799920

  3. Prodigiosin down-regulates survivin to facilitate paclitaxel sensitization in human breast carcinoma cell lines

    SciTech Connect

    Ho, T.-F.; Peng, Y.-T.; Chuang, S.-M.; Lin, S.-C.; Feng, B.-L.; Lu, C.-H.; Yu, W.-J.; Chang, J.-S. Chang, C.-C.

    2009-03-01

    Prodigiosin is a bacterial metabolite with potent anticancer activity, which is attributed to its proapoptotic effect selectively active in malignant cells. Still, the molecular mechanisms whereby prodigiosin induces apoptosis remain largely unknown. In particular, the role of survivin, a vital inhibitor of apoptosis, in prodigiosin-induced apoptosis has never been addressed before and hence was the primary goal of this study. Our results showed that prodigiosin dose-dependently induced down-regulation of survivin in multiple breast carcinoma cell lines, including MCF-7, T-47D and MDA-MB-231. This down-regulation is mainly regulated at the level of transcription, as prodigiosin reduced the levels of both survivin mRNA and survivin promoter activity but failed to rescue survivin expression when proteasome-mediated degradation is abolished. Importantly, overexpression of survivin rendered cells more resistant to prodigiosin, indicating an essential role of survivin down-regulation in prodigiosin-induced apoptosis. In addition, we found that prodigiosin synergistically enhanced cell death induced by paclitaxel, a chemotherapy drug known to up-regulate survivin that in turn confers its own resistance. This paclitaxel sensitization effect of prodigiosin is ascribed to the lowering of survivin expression, because prodigiosin was shown to counteract survivin induction by paclitaxel and, notably, the sensitization effect was severely abrogated in cells that overexpress survivin. Taken together, our results argue that down-regulation of survivin is an integral component mediating prodigiosin-induced apoptosis in human breast cancer cells, and further suggest the potential of prodigiosin to sensitize anticancer drugs, including paclitaxel, in the treatment of breast cancer.

  4. Intratumoral distribution of tritiated fluorodeoxyglucose in breast carcinoma: I. Are inflammatory cells important?

    SciTech Connect

    Brown, R.S.; Leung, J.Y.; Fisher, S.J.

    1995-10-01

    To investigate the contribution of various tumor components to tumor [{sup 3}H]FDG uptake, the size of proliferative cell and macrophage populations and the extent of necrosis, inflammatory infiltration and granulation tissue formation were evaluated in syngeneic rat mammary cancers (RMC) grown in immunocompetent rats, an animal tumor model that closely mimics human breast carcinoma. Tissue components of breast cancers grown in female Lewis rats (n=6) were identified histologically and immunohistochemically. Tracer uptake was studied by quantitative autoradiography 2 hr after an intravenous injection of 100 {mu}Ci [{sup 3}H]FDG. RMC tumors were glandular, with small foci of necrosis and were surrounded by a thin layer of granulation tissue. Tumors retained approximately 4% of the injected FDG dose (1.9 {plus_minus} 0.27 {mu}Ci/g). Macrophages numbered 0.5% of total cancer cells (1.2 {plus_minus} 1.0 of 246 {plus_minus} 77) and 18.0% {plus_minus} 3.9% of the nuclei of cancer cells were proliferating cell nuclear antigen (PCNA) positive (52 {plus_minus} 27 of 293 {plus_minus} 55). FDG uptake (in apparent disintegrations per minute per microgram of protein) in the cancer cell was 47.3 {plus_minus} 5.6, with the highest uptake in foci of high tumor cell density (82.1 {plus_minus} 6.3). Lower levels of FDG uptake were found in necrotic areas (19.8 {plus_minus} 22.9), granulation tissue (26.9 {plus_minus} 9.2) and areas of inflammatory infiltraton (20.5 {plus_minus} 15.5). These data suggest that FDG-PET imaging of untreated breast cancer mainly reflects tracer uptake in cancer cells. 45 refs., 4 figs., 2 tabs.

  5. Prevalence and characteristics of the MMTV-like associated breast carcinomas in Tunisia.

    PubMed

    Hachana, M; Trimeche, M; Ziadi, S; Amara, K; Gaddas, N; Mokni, M; Korbi, S

    2008-11-28

    The involvement of a retrovirus homologous to the mouse mammary tumor virus (MMTV) in the pathogenesis of human breast cancer (BC) has long been assumed, but has never been proven. Previous studies have reported the detection of MMTV-like env sequences in variable proportions that did not exceed 40% of BC cases in several countries. However, these viral sequences have been found in higher proportion (74%) in Tunisian diagnosed with BC during the seventies. This study is an attempt to evaluate the current prevalence of MMTV-like env gene in BC in Tunisian women. We used semi-nested PCR that amplify a 190-bp MMTV-like env sequence, followed by direct sequencing to screen a series of 122 cases of BC randomly selected. The findings were correlated to clinicopathological data and immunohistochemical expression status of progesterone and oestrogen receptors, HER2, and P53. Specific MMTV-like env sequences were found in 17 (13.9%) cases of breast carcinomas, whereas the same sequences were not detected in matched normal breast tissues. The presence of the viral sequences correlates inversely with progesterone receptor expression (6.8% versus 20.3%; P=0.03) and HER2 overexpression (3.1% versus 17.7%; P=0.04). This present study confirms the presence of MMTV-like env sequences in BC in Tunisian women but describes an important decrease in the prevalence of the viral sequences compared with previous studies. This reduction may be due to some changes in the virological characteristics or exposure to the virus. PMID:18639977

  6. Conservative surgery followed by radical radiotherapy in the management of stage I carcinoma of the breast

    SciTech Connect

    Baeza, M.R.; Arraztoa, J.; Sole, J.; Rodriguez, R.

    1982-10-01

    Since October 1976, the treatment policy in our Radiotherapy Center for Stage I carcinoma of the breast has been excision of the tumor mass, when it was cosmetically suitable, followed by irradiation to the breast and peripheral lymphatics. Eighty-three patients were admitted between October 1976 and March 1980. They underwent local excision of the tumor and then received 5000 rad in 5 weeks to the breast, supraclavicular, axillary and internal mammary chain lymph nodes. Each field was treated every day. A boost was then given to the scar, bringing the dose up to 6500 rad, calculated at maximum tumor depth, depending upon the size of the tumor prior to surgery. Cosmetic results were quite good, and the local control rate at 54 months is 98%. The survival with no evidence of disease (NED) at 54 months (acturarial) is 83%. There have been 10 failures: 8 distant, 1 local (in axilla, controlled by surgery, actually NED), and 1 local and distant (scar and brain). Both failures were found with 12 months after treatment, and 8/10 of the failures within 24 months. Twenty-one out of 83 patients have had complications (25.3%); of these, 28.8% were surgical and the remainder resulted from radiotherapy after surgery, either from radiotherapy alone or from combination of treatments. Of the total of 21 complications 18 were mild and 3 were serious. Of those 3 serious complications (3.6%), 2 were a result of radiotherapy, and one because an ill-advised axillary dissection prior to radiotherapy gave a negative axilla and a serious arm edema and painful shoulder. This was the worst complication in the total of 83 patients. These results compare favorably with the results achieved in the same Hospital with radical surgery as far as local tumor control and survival with no evidence of disease (NED) is concerned.

  7. Ovarian endometrioid carcinoma and endometriosis developing in a postmenopausal breast cancer patient during tamoxifen therapy: a case report and review of the literature.

    PubMed

    Cohen, I; Altaras, M M; Lew, S; Tepper, R; Beyth, Y; Ben-Baruch, G

    1994-12-01

    We present the first case of ovarian endometrioid carcinoma and endometriosis in a postmenopausal patient who was treated with tamoxifen for breast cancer. The association with prolonged unopposed estrogen-like stimulation with tamoxifen as a possible factor in the development of ovarian endometrioid carcinoma is discussed. PMID:7835785

  8. The impact of lobular carcinoma in situ in association with invasive breast cancer on the rate of local recurrence in patients with early-stage breast cancer treated with breast-conserving therapy

    SciTech Connect

    Jolly, Shruti; Kestin, Larry L. . E-mail: lkestin@beaumont.edu; Goldstein, Neal S.; Vicini, Frank A.

    2006-10-01

    Purpose: The significance of lobular carcinoma in situ (LCIS) associated with invasive breast cancer in patients undergoing breast-conserving therapy (BCT) remains controversial. We examined the impact of the presence and extent of LCIS associated with invasive breast cancer on clinical outcome in BCT patients. Methods and Materials: From 1980 to 1996, 607 cases of invasive breast cancer were treated with BCT. All slides were reviewed by a single pathologist. Positive margin was defined as presence of invasive carcinoma/ductal carcinoma in situ at the inked margin. Multiple clinical, pathologic, and treatment-related variables were analyzed for their association with ipsilateral breast tumor recurrence (IBTR) and true recurrence/marginal miss (TR/MM). Median follow-up was 8.7 years. Results: Fifty-six patients (9%) had LCIS in association with invasive cancer. On univariate analysis, positive final margin, positive/no reexcision, smaller maximum specimen dimension, and the presence of LCIS predicted for IBTR. The 10-year IBTR rate was 14% for cases with LCIS vs. 7% without LCIS (p = 0.04). On multivariate analysis, positive margin (p < 0.01), positive/no reexcision (p = 0.04), and presence of LCIS (p = 0.02) remained independently associated with IBTR; positive margin (p < 0.01) and LCIS (p = 0.04) were also associated with TR/MM failure. When examining only cases with negative final margins, the presence of LCIS remained associated with higher IBTR and TR/MM rates (p < 0.01). Conclusion: The presence of LCIS was independently associated with higher rate of IBTR and TR/MM after BCT for invasive breast cancer. LCIS may have significant premalignant potential and progress to an invasive IBTR at the site of index lesion. The adequacy of excision of LCIS associated with invasive carcinoma should be considered in patients undergoing BCT.

  9. The protective effects of paeonol against epirubicin-induced hepatotoxicity in 4T1-tumor bearing mice via inhibition of the PI3K/Akt/NF-kB pathway.

    PubMed

    Wu, Jing; Xue, Xia; Zhang, Bin; Jiang, Wen; Cao, Hongmei; Wang, Rongmei; Sun, Deqing; Guo, Ruichen

    2016-01-25

    Epirubicin is widely used for the treatment of various breast cancers; however, it has serious adverse side effects, such as hepatotoxicity, which require dose-adjustment or therapy substitution. Paeonol, an active component from Moutan Cortex, has a variety of biological activities, including preventing or reducing various toxicities induced by antineoplastics. Protection by paeonol against hepatotoxicity induced by epirubicin and the underlying mechanism of action were investigated in this study. Cytosolic enzymes in the serum and oxidative stress indices in the liver were determined. The protective effects were determined using the MTT assay in vitro or by evaluating the expression of apoptotic factors and crucial proteins in the PI3K/Akt/NF-kB pathway using western blot analysis. It is concluded that paeonol alleviates epirubicin-induced hepatotoxicity in 4T1-tumor bearing mice by inhibiting the PI3K/Akt/NF-kB pathway. PMID:26646421

  10. Adjuvant Radiation Therapy and Survival for Pure Tubular Breast Carcinoma-Experience From the SEER Database

    SciTech Connect

    Li Baoqing; Chen, Margaret; Nori, Dattatreyudu; Chao, K.S. Clifford; Chen, Allen M.; Chen, Steven L.

    2012-09-01

    Purpose: Pure tubular carcinoma of the breast (PTCB) represents a distinct subtype of invasive ductal carcinoma (IDC) that is generally thought to be associated with better prognosis than even low-grade IDC. There has been controversy as to the role of adjuvant radiation therapy (RT) in this population. We hypothesized that adjuvant RT would demonstrate a survival improvement. Methods and Materials: We queried the Surveillance, Epidemiology and End Results database for the years 1992-2007 to identify patients with pure tubular carcinomas of the breast. Patient demographics, tumor characteristics, and surgical and RT treatments were collected. Survival analysis was performed using the Kaplan-Meier method for univariate comparisons and Cox proportional hazards modeling for multivariate comparisons, stratifying on the basis of age with a cutoff age of 65. Results: A total of 6465 patients were identified: 3624 (56.1%) patients underwent lumpectomy with RT (LUMP+RT), 1525 (23.6%) patients underwent lumpectomy alone (LUMP), 1266 (19.6%) patients received mastectomy alone (MAST), and 50 (0.8%) patients underwent mastectomy with RT (MAST+RT). When we compared the LUMP+RT and LUMP groups directly, those receiving adjuvant RT tended to be younger and were less likely to be hormone receptor-positive. Overall survival was 95% for LUMP+RT and 90% for LUMP patients at 5 years. For those 65 or younger, the absolute overall survival benefit of LUMP+RT over LUMP was 1% at 5 years and 3% at 10 years. On stratified multivariate analysis, adjuvant RT remained a significant predictor in both age groups (P=.003 in age {<=}65 and P=.04 in age >65 patients). Other significant unfavorable factors were older age and higher T stage (age >65 only). Conclusions: Since sufficiently powered large scale clinical trials are unlikely, we would recommend that adjuvant radiation be considered in PTCB patients age 65 or younger, although consideration of the small absolute survival benefit is

  11. Runx2 Expression as a Potential Prognostic Marker in Invasive Ductal Breast Carcinoma.

    PubMed

    El-Gendi, Saba Mohamed; Mostafa, Mohamed Farouk

    2016-07-01

    The Runx family of transcription factors has been implicated in cancer progression, both positively and negatively. Recent studies assigned a role for Runx2 in promoting breast cancer metastasis. However, the role of Runx2 during the early stage of breast carcinoma and its association with clinical outcomes remain unknown. Assessing the clinicopathological significance of Runx2 expression in a cohort of breast invasive ductal carcinomas (IDC). The correlation of nuclear Runx2 LI with clinicopathological parameters was assessed in 84 IDCs. To study the association of Runx2 with patient outcomes, in addition to treating it as a continuous variable, Runx2 was categorized by its median value (65) and by an additional two cut-off points determined by ROC curve analyses, at 45 for disease free survival (DFS) and 40 for overall survival (OS). Multivariate Cox regression models were also constructed. We used the best subset regression to identify models that predict DFS and OS with as few predictors as possible, and validation was performed. Based on the "Predicted R(2)", the three best models were identified. Using Cox-regression, the interaction between Runx2 and other clinicopathological terms was tested. Runx2 LI was significantly associated only with positive Her-2 status, and did not correlate significantly with other clinicopathological parameters. Although Runx2 LI, in the continuous form and when categorized by the median, did not correlate significantly with DFS and OS; after it was categorized using the optimal cut-off points determined using ROC curve analysis, the patients with Runx2 LI >45 % showed a significantly higher event rate and shorter DFS (P = 0.047), whereas patients with Runx2 LI >40 % showed a significantly shorter OS (P = 0.050). Moreover, Runx2 LI contributed significantly in the models built to predict DFS and OS. For DFS, no interaction terms contributed significantly to the models. However, among stage IV cases, the interaction term

  12. Mixed gastric carcinoma with intestinal and cribriform patterns: a distinctive pathologic appearance associated with poor prognosis in advanced stages and a potential mimicker of metastatic breast carcinoma.

    PubMed

    Lino-Silva, Leonardo Saúl; Salcedo Hernández, Rosa Angélica; Molina-Frías, Ernesto

    2013-02-01

    Gastric adenocarcinoma is characterized by marked heterogeneity at cytological and architectural level and frequently shows overlap between microscopic patterns. This article describes a peculiar pattern of gastric adenocarcinoma, previously unreported, that combines intestinal type adenocarcinoma with areas of cribriform pattern that resembles both architectural and cytological in situ ductal carcinoma of the breast and to the best of the authors' knowledge, there are no earlier reports of this pattern in the stomach, which has been named "gastric carcinoma with cribriform component (CGA). The authors analyzed 12 cases of intestinal type adenocarcinoma with areas at least 20% of cribriform pattern (range from 20% to 90%) that was present in 9% of intestinal type gastric adenocarcinomas in their institution. There is slight predilection for male sex, and the median age of presentation is 55.8 years. The phenotype by immunohistochemistry is the same as with conventional (non-CGA) carcinomas. CGA shows more frequent lymphovascular invasion (P = .039), perineural invasion (P = .027) and resembles both in situ and invasive cribriform carcinoma of the breast. In clinical stage III the overall 3-year survival of CGA was worse than those with non-CGA component (38.6% vs 25%; 3-year survival, P = .010) and proves to be an independent adverse factor for overall survival in a multivariate analysis. Compared with conventional gastric carcinomas, CGA is deep infiltrating, has more nodal metastases, more lymphovascular and perineural invasion, and has decreased overall survival. Thus, proper recognition and report is important, even in small biopsies or small foci. PMID:22744963

  13. Quantitative microscopic evaluation of mucin areas and its percentage in mucinous carcinoma of the breast using tissue histological images.

    PubMed

    Saha, Monjoy; Arun, Indu; Basak, Bijan; Agarwal, Sanjit; Ahmed, Rosina; Chatterjee, Sanjoy; Bhargava, Rohit; Chakraborty, Chandan

    2016-06-01

    Mucinous carcinoma (MC) of the breast is very rare (∼1-7% of all breast cancers), invasive ductal carcinoma. Presence of pools of extracellular mucin is one of the most important histological features for MC. This paper aims at developing a quantitative computer-aided methodology for automated identification of mucin areas and its percentage using tissue histological images. The proposed method includes pre-processing (i.e., colour space transformation and colour normalization), mucin regions segmentation, post-processing, and performance evaluation. The proposed algorithm achieved 97.74% segmentation accuracy in comparison to ground truths. In addition, the percentage of mucin present in the tissue regions is calculated by the mucin index (MI) for grading MC (pure, moderately, minimally mucinous). PMID:26971129

  14. Identification of lesion subtypes in biopsies of ductal carcinoma in situ of the breast using biomarker ratio imaging microscopy.

    PubMed

    Clark, Andrea J; Petty, Howard R

    2016-01-01

    Although epidemiological studies propose aggressive and non-aggressive forms of ductal carcinoma in situ (DCIS), they cannot be identified with conventional histopathology. We now report a retrospective study of human biopsy samples using biomarker ratio imaging microscopy (BRIM). Using BRIM, micrographs of biomarkers whose expression correlates with breast cancer aggressiveness are divided by micrographs of biomarkers whose expression negatively correlates with aggressiveness to create computed micrographs reflecting aggressiveness. The biomarker pairs CD44/CD24, N-cadherin/E-cadherin, and CD74/CD59 stratified DCIS samples. BRIM identified subpopulations of DCIS lesions with ratiometric properties resembling either benign fibroadenoma or invasive carcinoma samples. Our work confirms the existence of distinct subpopulations of DCIS lesions, which will likely have utility in breast cancer research and clinical practice. PMID:27247112

  15. Identification of lesion subtypes in biopsies of ductal carcinoma in situ of the breast using biomarker ratio imaging microscopy

    PubMed Central

    Clark, Andrea J.; Petty, Howard R.

    2016-01-01

    Although epidemiological studies propose aggressive and non-aggressive forms of ductal carcinoma in situ (DCIS), they cannot be identified with conventional histopathology. We now report a retrospective study of human biopsy samples using biomarker ratio imaging microscopy (BRIM). Using BRIM, micrographs of biomarkers whose expression correlates with breast cancer aggressiveness are divided by micrographs of biomarkers whose expression negatively correlates with aggressiveness to create computed micrographs reflecting aggressiveness. The biomarker pairs CD44/CD24, N-cadherin/E-cadherin, and CD74/CD59 stratified DCIS samples. BRIM identified subpopulations of DCIS lesions with ratiometric properties resembling either benign fibroadenoma or invasive carcinoma samples. Our work confirms the existence of distinct subpopulations of DCIS lesions, which will likely have utility in breast cancer research and clinical practice. PMID:27247112

  16. Adenomyoepithelioma with carcinoma of the breast: A report of two cases and a review of the literature.

    PubMed

    Xu, Jing; Tang, Xiaoyan; Iida, Yuko; Fuchinoue, Fumi; Kusumi, Tomomi; Yagihashi, Norito; Kawachi, Kae; Shimizu, Satoru; Masuda, Shinobu

    2016-02-01

    We herein described two cases of adenomyoepithelioma (AME) with carcinoma of the breast. Both of them were Japanese women, and they presented with a mass in their breast. Post-operative specimens revealed encapsulated and well-circumscribed tumors with local invasion, necrosis, cytological atypia, and a high mitotic rate. In immunohistochemistry, coincidentally with the loose adhesion pattern of myoepithelial cells in both cases, the intensities of E-cadherin and beta-catenin were much weaker in myoepithelial than luminal epithelial cells, with almost negative finding of beta-catenin in one case. We first found deletion of CDH1 and polysomy of CEP16 in myoepithelial cells by double color-fluorescence in situ hybridization. The two cases have been followed up for 5-8 years, and both remained free from local recurrence and distant metastases. We also presented an overview of 47 cases of AME with carcinoma in English-language literatures. PMID:26596263

  17. Genetic Variations in ABCG2 Gene Predict Breast Carcinoma Susceptibility and Clinical Outcomes after Treatment with Anthracycline-Based Chemotherapy

    PubMed Central

    Wu, Huizhe; Liu, Yong; Kang, Hui; Xiao, Qinghuan; Yao, Weifan; Zhao, Haishan; Wang, Enhua; Wei, Minjie

    2015-01-01

    The genetic variants of the ATP-binding cassette, subfamily G, member 2 (ABCG2) are known to be involved in developing cancer risk and interindividual differences in chemotherapeutic response. The polymorphisms in ABCG2 gene were genotyped by using PCR-RFLP assays. We found that ABCG2 G34A GA/AA genotype, C421A AA genotype, and haplotypes 34A-421C and 34G-421A were significantly associated with increased risk for developing breast carcinoma. Furthermore, ABCG2 C421A AA homozygote had a significant enhanced therapeutic response in patients with neoadjuvant anthracycline-based chemotherapy. Moreover, ABCG2 G34A AA genotype carriers displayed a longer OS in ER positive patients or PR positive patients after postoperative anthracycline-based chemotherapy. These results suggested that the ABCG2 polymorphisms might be a candidate pharmacogenomic factor to assess susceptibility and prognosis for breast carcinoma patients. PMID:26634205

  18. FOXA2 mRNA expression is associated with relapse in patients with Triple-Negative/Basal-like breast carcinoma.

    PubMed

    Perez-Balaguer, Ariadna; Ortiz-Martínez, Fernando; García-Martínez, Araceli; Pomares-Navarro, Critina; Lerma, Enrique; Peiró, Gloria

    2015-09-01

    The FOXA family of transcription factors regulates chromatin structure and gene expression especially during embryonic development. In normal breast tissue FOXA1 acts throughout mammary development; whereas in breast carcinoma its expression promotes luminal phenotype and correlates with good prognosis. However, the role of FOXA2 has not been previously studied in breast cancer. Our purpose was to analyze the expression of FOXA2 in breast cancer cells, to explore its role in breast cancer stem cells, and to correlate its mRNA expression with clinicopathological features and outcome in a series of patients diagnosed with breast carcinoma. We analyzed FOXA2 mRNA expression in a retrospective cohort of 230 breast cancer patients and in cell lines. We also knocked down FOXA2 mRNA expression by siRNA to determine the impact on cell proliferation and mammospheres formation using a cancer stem cells culture assay. In vitro studies demonstrated higher FOXA2 mRNA expression in Triple-Negative/Basal-like cells. Further, when it was knocked down, cells decreased proliferation and its capability of forming mammospheres. Similarly, FOXA2 mRNA expression was detected in 10% (23/230) of the tumors, especially in Triple-Negative/Basal-like phenotype (p < 0.001, Fisher's test). Patients whose tumors expressed FOXA2 had increased relapses (59 vs. 79%, p = 0.024, log-rank test) that revealed an independent prognostic value (HR = 3.29, C.I.95% = 1.45-7.45, p = 0.004, Cox regression). Our results suggest that FOXA2 promotes cell proliferation, maintains cancer stem cells, favors the development of Triple-Negative/Basal-like tumors, and is associated with increase relapses. PMID:26298189

  19. 18F-FDG PET/CT Imaging of Bilateral Renal Metastasis of Breast Adenoid Cystic Carcinoma.

    PubMed

    Hassoun, Hani; Alabed, Yazan Z; Karls, Shawn; Probst, Stephan; Laufer, Jerome

    2016-02-01

    We report the case of a 65-year-old woman with a history of adenoid cystic carcinoma (ACC) of the breast. Fifteen years after mastectomy, the patient underwent a right upper lobectomy for a lung mass, and biopsy indicated ACC metastasis. Ten years after lobectomy, an F-FDG PET/CT was performed for restaging to rule out further metastases. We observed intense FDG uptake in enlarged polylobulated kidneys, which was biopsy proven as ACC metastasis. PMID:26562575

  20. A new rabbit monoclonal E-cadherin antibody [EP700Y] shows higher sensitivity than mouse monoclonal E-cadherin [HECD-1] antibody in breast ductal carcinomas and does not stain breast lobular carcinomas.

    PubMed

    Hoang, Laura L; Tang, Ping; Hicks, David G; Chen, Huijiao; Yang, Qi; Haas, Thomas S; Bremer, Ryan E; Tacha, David

    2014-09-01

    Immunohistochemical studies have shown E-cadherin to be expressed in breast carcinomas showing a ductal histology, with a corresponding loss of expression in tumors with a lobular histology. As a result, mouse monoclonal anti-E-cadherin [HECD-1] has been used by pathologists to differentiate between ductal and lobular carcinomas, with currently published sensitivity and specificity rates of approximately 90%. Rabbit monoclonal antibodies may combine the best properties of both mouse monoclonal antibodies and rabbit antisera. Therefore, this study compares the staining sensitivity and specificity of a new rabbit monoclonal E-cadherin and the standard mouse monoclonal E-cadherin [HECD-1] in breast ductal carcinomas, and evaluates a cocktail of rabbit monoclonal E-cadherin and p120 catenin in the discrimination of ductal from lobular carcinomas. The rabbit E-cadherin showed sharper staining and increased sensitivity (80/81, 99%) than the mouse E-cadherin (75/81, 93%). The rabbit E-cadherin achieved a score of 3+ in 85.2% (69/81) of cases as compared with a 3+ in only 21.0% (17/81) of cases stained with mouse E-cadherin. All lobular carcinomas (n=37) were confirmed by the absence of E-cadherin and the diffuse cytoplasmic expression of p120 catenin. Although both the single mouse E-cadherin and dual stain can differentiate ductal from lobular lesions, the dual stain is helpful in challenging cases because of its bright pink p120 catenin and dark brown rabbit E-cadherin staining. The highly sensitive rabbit E-cadherin antibody is the preferred antibody for evaluating ductal carcinomas and for distinguishing ductal versus lobular lesions, and the dual stain was superior to the single E-cadherin stain. PMID:24569788

  1. Radiologic Findings of Ductal Carcinoma in Situ Arising Within a Juvenile Fibroadenoma: Mammographic, Sonographic and Dynamic Contrast-Enhanced Breast MRI Features.

    PubMed

    Park, Eun Kyung; Cho, Kyu Ran; Seo, Bo Kyoung; Woo, Ok Hee; Lee, Jeong Hyeon; Song, Sung Eun; Bae, Jeong Won

    2015-04-01

    Juvenile fibroadenoma is an uncommon histologic variant of fibroadenoma that frequently shows a remarkable and rapid growth. The development of a carcinoma within a fibroadenoma, either in situ or invasive, is a rare condition. We encountered a 36-year-old woman with a palpable mass in the right breast. The radiologic findings were indicative of a fibroadenoma in the breast. Sonographic guided biopsy using a 14G core needle revealed the presence of ductal carcinoma in situ (DCIS) within the juvenile fibroadenoma. Focal excision was performed and the patient underwent radiation therapy in the right breast after surgery. PMID:26060554

  2. Radiologic Findings of Ductal Carcinoma in Situ Arising Within a Juvenile Fibroadenoma: Mammographic, Sonographic and Dynamic Contrast-Enhanced Breast MRI Features

    PubMed Central

    Park, Eun Kyung; Cho, Kyu Ran; Seo, Bo Kyoung; Woo, Ok Hee; Lee, Jeong Hyeon; Song, Sung Eun; Bae, Jeong Won

    2015-01-01

    Juvenile fibroadenoma is an uncommon histologic variant of fibroadenoma that frequently shows a remarkable and rapid growth. The development of a carcinoma within a fibroadenoma, either in situ or invasive, is a rare condition. We encountered a 36-year-old woman with a palpable mass in the right breast. The radiologic findings were indicative of a fibroadenoma in the breast. Sonographic guided biopsy using a 14G core needle revealed the presence of ductal carcinoma in situ (DCIS) within the juvenile fibroadenoma. Focal excision was performed and the patient underwent radiation therapy in the right breast after surgery. PMID:26060554

  3. Preoperative breast magnetic resonance imaging and contralateral breast cancer occurrence among older women with ductal carcinoma in situ.

    PubMed

    Wang, Shi-Yi; Long, Jessica B; Killelea, Brigid K; Evans, Suzanne B; Roberts, Kenneth B; Silber, Andrea; Gross, Cary P

    2016-07-01

    Although preoperative magnetic resonance imaging (MRI) can detect mammographically occult contralateral breast cancers (CBCs) among women with ductal carcinoma in situ (DCIS), the impact of MRI on the incidence of subsequent CBC events is unclear. We examined whether MRI use decreases CBC occurrences and detection of invasive disease among women who develop a CBC. Utilizing the Surveillance, Epidemiology, and End Results-Medicare dataset, we assessed overall, synchronous (<6 months after primary cancer diagnosis), and subsequent (≥6 months after diagnosis, i.e., metachronous) CBC occurrence in women aged 67-94 years diagnosed with DCIS during 2004-2009, with follow-up through 2011. We applied a matched propensity score approach to compare the stage-specific incidence rate of CBC according to MRI use. Our sample consisted of 9166 beneficiaries, 1258 (13.7 %) of whom received preoperative MRI. After propensity score matching, preoperative MRI use was significantly associated with a higher synchronous CBC detection rate (108.6 vs. 29.7 per 1000 person-years; hazard ratio [HR] = 3.65; p < .001) with no significant differences in subsequent CBC rate (6.7 vs. 6.8 per 1000 person-years; HR = 0.90; p = .71). The 6-year cumulative incidence of any CBC (in situ plus invasive) remained significantly higher among women undergoing MRI, compared with those not undergoing MRI (9 vs. 4 %, p < .001). Women undergoing MRI also had a higher incidence of invasive CBC (4 vs. 3 %, p = .04). MRI use resulted in an increased detection of synchronous CBC but did not prevent subsequent CBC occurrence, suggesting that many of the undetected CBC lesions may not become clinically evident. PMID:27287780

  4. Expression of multidrug resistance proteins in invasive ductal carcinoma of the breast.

    PubMed

    Li, Weiquan; Song, Maomin

    2014-11-01

    Chemotherapy is commonly used for the treatment of breast cancer. However, the resistance to chemotherapeutic agents, often mediated by multidrug resistance (MDR) mechanisms, is a common occurrence. The present study examined the expression of several MDR-related proteins (MRPs) in invasive ductal carcinoma (IDC) of the breast, and assessed their association with clinicopathological variables and their prognostic significance. In addition, immunohistochemistry was used to measure the expression of MRP, p-glycoprotein (P-gp), topoisomerase 2α (Topo2α), thymidylate synthase (TS) and glutathione-S-transferase π (GST-π) in 156 resected IDCs of the breast. Pearson's χ(2) test and Spearman's correlation coefficient were used to analyze the association between MDR protein expression and several clinicopathological variables. The association between each of the five MDR proteins was also examined. Furthermore, Kaplan-Meier analysis and Cox regression modeling were used to assess overall survival. The expression of MRP, P-gp, Topo2α, TS and GST-π was detected in 20.5% (32/156), 25.0% (39/156), 84.0% (131/156), 41.7% (65/156) and 41.0% (64/156) of cases examined, respectively. No correlation was identified between MRP and Topo-2α and the clinicopathological variables examined. By contrast, P-gp (χ(2)=20.226; P<0.0001) and GST-π (χ(2)=35.032; P<0.0001) were found to positively correlate with tumor grade. In addition, staining for TS was associated with axillary lymph node metastasis (χ(2)=42.281; P<0.0001). The expression levels of P-gp and GST-π were found to be significantly correlated (r= 0.319; P<0.0001). Furthermore, GST-π expression was elevated in estrogen receptor-negative breast cancer (χ(2)=17.407; P<0.0001). Tumor histological grade, in addition to TS and GST-π expression, were significant predictors of a poor survival outcome. TS and GST-π are consequently useful prognostic biomarkers in IDC, therefore, when establishing a personalized

  5. Retinoblastoma (RB1) gene product expression in breast carcinoma. Correlation with Ki-67 growth fraction and biopathological profile.

    PubMed Central

    Ceccarelli, C; Santini, D; Chieco, P; Taffurelli, M; Gamberini, M; Pileri, S A; Marrano, D

    1998-01-01

    AIMS: To investigate the expression of retinoblastoma protein (pRb) in invasive breast tumours and compare its expression with the major biopathological prognostic indicators to identify more aggressive subgroups. MATERIAL: Archival paraffin embedded tissues from 153 consecutive primary breast carcinomas. METHODS: pRb, Ki-67, and oestrogen receptor/progesterone receptor proteins were identified by immunohistochemistry and score values were recorded by image cytometric analysis; p53 and EGFr expression was also evaluated. RESULTS: pRb scores correlated strongly with proliferation activity as determined by Ki-67 staining. Positive relations were also observed between pRb scores, tumour size, nuclear and histological grade, and oestrogen receptor/progesterone receptor content, while abnormal p53 accumulation was not associated with pRb expression. Among the high proliferating carcinomas it was possible to identify 13 cases with loss of pRb expression. CONCLUSIONS: pRb expression paralleled proliferative activity in the majority of breast carcinomas examined, suggesting that in these cases the protein behaves normally in regulating the cell cycle. Conversely in cases with loss of pRb immunostaining, the combined expression of specific highly aggressive factors (EGFr and p53 expression, oestrogen receptor/progesterone receptor negative status, and high K67) seems to characterise a more aggressive phenotype showing growth advantage and cellular "progression" rather than significant nodal involvement. Images PMID:10193322

  6. [Synchronous and ipsilateral invasive ductal carcinoma of the breast occurring near a phyllodes tumor - a case report].

    PubMed

    Nagashima, Saki; Sakurai, Kenichi; Suzuki, Shuhei; Sakagami, Masashi; Enomoto, Katsuhisa; Amano, Sadao; Koshinaga, Tsugumichi

    2014-11-01

    We report 2 cases of invasive ductal carcinoma of the breast occurring near a phyllodes tumor. The first case was ofa 58- year-old woman who had a tumor in her right breast and visited our hospital. Following a core needle biopsy (CNB), a malignant phyllodes tumor was diagnosed. We performed a lumpectomy for the phyllodes tumor, with 1.5-cm surgical margins. Pathological diagnosis of the resected specimen confirmed the malignant phyllodes tumor. A ductal carcinoma in situ (DCIS) was also discovered near the phyllodes tumor. The second case was of another 58-year-old woman who had a big tumor in her right breast and visited our hospital. CNB resulted in pathological diagnosis ofa benign phyllodes tumor. The tumor was removed by a lumpectomy with 1.5-cm surgical margins. The pathological diagnosis from the resected specimen was borderline phyllodes tumor with invasive ductal carcinoma in the proximity. In both cases, DCIS could not have been diagnosed preoperatively. PMID:25731391

  7. The integrin alpha 6 beta 1 promotes the survival of metastatic human breast carcinoma cells in mice.

    PubMed Central

    Wewer, U. M.; Shaw, L. M.; Albrechtsen, R.; Mercurio, A. M.

    1997-01-01

    The role of the integrin alpha 6 beta 1 in breast carcinoma progression was studied by targeted elimination of this integrin in MDA-MB-435 cells, a human breast carcinoma cell line that is highly metastatic in athymic mice. The strategy used is based on the finding that expression of a cytoplasmic domain deletion mutant of the beta 4-integrin subunit (beta 4-delta CYT) in MDA-MB-435 cells eliminates formation of the alpha 6 beta 1 heterodimer. MDA-MB-435 cells that lacked alpha 6 beta 1 expression (beta 4-delta CYT transfectants) formed tumors in athymic mice that were suppressed in their growth and that exhibited a significant increase in apoptosis in comparison to the control tumors. Unlike the control MDA-MB-435 cells, the beta 4-delta CYT transfectants were unable to establish metastatic foci in the lungs. Also, the control transfectants grew substantially better than the beta 4-delta CYT transfectants in the liver after intrahepatic injection because of extensive apoptosis in the beta 4-delta CYT transfectants. These data suggest that a major function of the alpha 6 beta 1 integrin in breast carcinoma is to facilitate tumorigenesis and promote tumor cell survival in distant organs. Images Figure 1 Figure 2 Figure 3 PMID:9358743

  8. Immunolocalization and gene expression of oxytocin receptors in carcinomas and non-neoplastic tissues of the breast.

    PubMed Central

    Bussolati, G.; Cassoni, P.; Ghisolfi, G.; Negro, F.; Sapino, A.

    1996-01-01

    Recent evidence indicates that oxytocin (OT), in addition to the induction of myometrial and myoepithelial cell contraction, can influence proliferation and differentiation in developing mammary glands and in breast cancer cells, hence the interest in detecting and locating OT receptors (OTRs). We produced rabbit antisera and a monoclonal antibody against a synthetic peptide corresponding to the carboxy terminus of the predicted OTR sequence. We tested their specificity in immunoblasts and immunocytochemical tests. All of the antibodies specifically stained myometrium (at term of pregnancy). In the human breast, OTRs were detected in myoepithelial cells along ducts of normal lobules and in sclerosing adenosis. Intraductal cells in benign hyperplastic lesions were also positive. OTRs were demonstrated in cases of primary and metastatic carcinomas of the breast. In the same tissues, OTR gene expression was shown by reverse transcriptase polymerase chain reaction procedures detecting the specific mRNA. These results suggest that the interaction between OT and its receptors might play a role in the origin and evolution of non-neoplastic lesions and carcinomas of the breast. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 PMID:8669475

  9. The management of breast carcinoma by primary radiotherapy of Mount Sinai hospital from 1962-1979. [/sup 60/Co; Betatron

    SciTech Connect

    Balawajder, I.; Antich, P.P.; Boland, J.

    1982-04-15

    Two-hundred eight patients with carcinoma of the breast were treated with megavoltage irradiation as the primary method of local management at Mount Sinai Hospital between 1962-1979. The effects of treatment volume, technique, and other parameters are discussed for the Stage I and II patients, together with the importance of tumor size and nodal status in control of local disease and distant metastases. In this series the cumulative probability of freedom from metastases is 93 +/- 5% when the irradiation is confined to the breast and axilla as compared with 72 +/- 9% when extended fields are used, with no difference in local control. Based on these results it was decided to confine irradiation to the breast and axilla alone in the majority of early stage cancer patients. Recommendations are made for radiation techniques and dosages to optimize control of the disease, minimize complications, and facilitate systemic therapy in patients with positive nodes.

  10. Breast adenomyoepithelioma and adenomyoepithelioma with carcinoma (malignant adenomyoepithelioma) with associated breast malignancies: A case series emphasizing histologic, radiologic, and clinical correlation.

    PubMed

    Moritz, August W; Wiedenhoefer, James F; Profit, Amanda P; Jagirdar, Jaishree

    2016-10-01

    The 2012 World Health Organization (WHO) classification of breast tumors distinguishes adenomyoepitheliomas (AMEs) as benign tumors composed of a biphasic proliferation of phenotypically variable myoepithelial cells around small epithelial lined spaces. Many AMEs have demonstrated benign behavior and are often cured with excision with negative margins, but some have exhibited malignant transformation of the myoepithelial cells, ductal epithelial cells, or both. When one of the components is histologically malignant, it is termed AME with carcinoma. Due to the rarity, the literature correlating imaging, histology, and clinical outcome is limited. A retrospective review was undertaken. A review of an institutional pathology database identified 14 cases with AME or malignant AME. Most AMEs had nonspecific imaging findings and were categorized as Bi-Rads 4. Histologic features of AME did not correlate with prior or concurrent breast malignancies or any radiographic features. Clinical follow up could be obtained for all but one case (mean follow up time = 75 months). 5 cases had no known treatment post-biopsy and 5 patients received mastectomy. No recurrences were noted. 3/13 cases of benign AME had associated breast malignancies including invasive ductal adenocarcinoma and ductal carcinoma in-situ. 1 case of malignant AME had a synchronous separate malignant phyllodes tumor. Given the unclear and unpredictable propensity for malignant transformation, conservative excision with negative margins currently seems appropriate. PMID:27494340

  11. TACC2 (transforming acidic coiled-coil protein 2) in breast carcinoma as a potent prognostic predictor associated with cell proliferation.

    PubMed

    Onodera, Yoshiaki; Takagi, Kiyoshi; Miki, Yasuhiro; Takayama, Ken-Ichi; Shibahara, Yukiko; Watanabe, Mika; Ishida, Takanori; Inoue, Satoshi; Sasano, Hironobu; Suzuki, Takashi

    2016-08-01

    Transforming acidic coiled-coil protein 2 (TACC2) belongs to TACC family proteins and involved in a variety of cellular processes through interactions with some molecules involved in centrosomes/microtubules dynamics. Mounting evidence suggests that TACCs is implicated in the progression of some human malignancies, but significance of TACC2 protein in breast carcinoma is still unknown. Therefore, in this study, we examined the clinical significance of TACC2 in breast carcinoma and biological functions by immunohistochemistry and in vitro experiments. Immunohistochemistry for TACC2 was performed in 154 cases of invasive ductal carcinoma. MCF-7 and MDA-MB-453 breast carcinoma cell lines were transfected with small interfering RNA (siRNA) for TACC2, and subsequently, cell proliferation, 5-Bromo-2'-deoxyuridine (BrdU), and invasion assays were performed. TACC2 immunoreactivity was detected in 78 out of 154 (51%) breast carcinoma tissues, and it was significantly associated with Ki-67 LI. The immunohistochemical TACC2 status was significantly associated with increased incidence of recurrence and breast cancer-specific death of the patients, and multivariate analyses demonstrated TACC2 status as an independent prognostic factor for both disease-free and breast cancer-specific survival. Subsequent in vitro experiments showed that TACC2 significantly increased the proliferation activity of MCF-7 and MDA-MB-453. These results suggest that TACC2 plays an important role in the cell proliferation of breast carcinoma and therefore immunohistochemical TACC2 status is a candidate of worse prognostic factor in breast cancer cases. PMID:27333920

  12. 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

  13. Clinical Outcomes Using Accelerated Partial Breast Irradiation in Patients With Invasive Lobular Carcinoma

    SciTech Connect

    Shah, Chirag; Wilkinson, J. Ben; Shaitelman, Simona; Grills, Inga; Wallace, Michelle; Mitchell, Christina; Vicini, Frank

    2011-11-15

    Purpose: We compared clinical outcomes of women diagnosed with either invasive lobular carcinoma (ILC) or invasive ductal carcinoma (IDC) treated with accelerated partial breast irradiation (APBI). Methods and Materials: A total of 16 patients with ILC received APBI as part of their breast-conservation therapy (BCT) and were compared with 410 patients with IDC that received APBI as part of their BCT. Clinical, pathologic, and treatment related variables were analyzed including age, tumor size, hormone receptor status, surgical margins, lymph node status, adjuvant hormonal therapy, adjuvant chemotherapy, and APBI modality. Clinical outcomes including local recurrence (LR), regional recurrence (RR), disease-free survival (DFS), cause-specific survival (CSS), and overall survival (OS) were analyzed. Results: Median follow-up was 3.8 years for the ILC patients and 6.0 years for the IDC patients. ILC patients were more likely to have positive margins (20.0% vs. 3.9%, p = 0.006), larger tumors (14.1 mm vs. 10.9 mm, p = 0.03) and less likely to be node positive (0% vs. 9.5%, p < 0.001) when compared with patients diagnosed with IDC. The 5-year rate of LR was 0% for the ILC cohort and 2.5% for the IDC cohort (p = 0.59). No differences were seen in the rates of RR (0% vs. 0.7%, p = 0.80), distant metastases (0% vs. 3.5%, p = 0.54), DFS (100% vs. 94%, p = 0.43), CSS (100% vs. 97%, p = 0.59), or OS (92% vs. 89%, p = 0.88) between the ILC and IDC patients, respectively. Additionally, when node-positive patients were excluded from the IDC cohort, no differences in the rates of LR (0% vs. 2.2%, p = 0.62), RR (0% vs. 0%), DFS (100% vs. 95%, p = 0.46), CSS (100% vs. 98%, p = 0.63), or OS (92% vs. 89%, p = 0.91) were noted between the ILC and IDC patients. Conclusion: Women with ILC had excellent clinical outcomes after APBI. No difference in local control was seen between patients with invasive lobular versus invasive ductal histology.

  14. Association of ultrasonographic features with NGX6 expression and prognosis in invasive ductal breast carcinoma

    PubMed Central

    Xiao, Jidong; Zhou, Yuanquan; Zhu, Wenhui

    2015-01-01

    Introduction: Nasopharyngeal carcinoma-associated gene 6 (NGX6) is a newly discovered tumor suppressor gene. It contains one epidermal growth factor (EGF)-like domain. Many studies have shown that proteins contain (EGF)-like domain structure affect a variety of biological actions. However, little is known about the relationships between NGX6 expression and biological behaviors in invasive ductal breast carcinoma (IDBC). The study discussed the association of ultrasonographic features with NGX6 expression and prognosis in IDBC. Methods: Ultrasonographic feature and clinical data in 122 patients with IDBC were retrospectively analyzed. NGX6 expression of IDBC was measured using immunohistochemistry methods. Results: The incidence of the burr sign, lymph node metastasis and abundance blood flow in NGX6 expression negative groups were higher than those in positive groups. Kaplan-Meier analysis showed that the association between NGX6 positive expression and higher disease-free survival (DFS) or higher overall survival (OS); Lymph node metastasis is associated with lower DFS or lower OS; Lower blood flow grade is associated with higher DFS. In univariate and multivariate survival analysis, NGX6 expression, lymph node metastasis, TNM and the blood flow grade were the independent prognostic factors for DFS and OS of IDBC. Conclusions: ultrasonographic features are associated with NGX6 expression in IDBC. NGX6 is involved in the invasion and metastasis activity of IDBC. Our results suggest that NGX6 may be employed as a promising prognostic factor and useful therapeutic target for IDBC. Combination of ultrasonic findings and NGX6 detection may yield clinically useful information for IDBC prognosis. PMID:26261522

  15. Molecular cloning and characterization of a 20q13.2 amplicon in breast carcinoma

    SciTech Connect

    Collins, C.; Froula, J.; Kowbel, D.

    1994-09-01

    Comparative genomic hybridization (CGH) has identified an amplification event involving chromosome band 20q13.2 in 15-20% of primary breast carcinomas. The application of FISH to the study of tumor interphase nuclei using 33 locus specific cosmid and P1 probes revealed amplification of band 20q13.2 in 35% of breast cancer cell lines and 8% of primary tumors. Moreover, this study localized the amplification event to the 1.5Mb interval defined by (Flpter 0.80-0.84.) and excluded all known genes in the region as candidates for the putative oncogene(s). To both identify the putative oncogene(s) and characterize the amplicon, a 12 member 4Mb YAC contig has been assembled by STS mapping that spans the core of the amplicon. The YAC contig is now being converted to a P1 contig to facilitate sequencing, exon trapping and direct selection of cDNAs. This is being accomplished by performing interAlu PCR reactions on individual YACs and sequencing the reaction products to create 5-10 new STSs per megaYAC. The DuPont P1 library is then screened for these STSs by the PCR. To date 21 P1 clones, forming 6 contigs, have been isolated by screening the DuPont P1 library for existing and/or newly created STSs. The ends of the 21 P1 clones are being sequenced to facilitate contig alignment and to enable chromosome walking. In collaboration with the Human Genome Center at the Lawrence Berkeley Laboratory we have initiated the directed sequencing of two P1 contigs, localized within the amplicon core, and ultimately will sequence the entire 1-2Mb amplicon.

  16. HER-2/neu protein-receptor-positive breast carcinoma: an immunologic perspective.

    PubMed

    Brown, R E; Bernath, A M; Lewis, G O

    2000-07-01

    Immunotherapy using a monoclonal antibody against the human epidermal growth factor receptor 2 protein, HER-2/neu, has proven to be clinically efficacious in about one-half of breast cancer patients who exhibit strong (3+) plasmalemmal immunoreactivity for this protein. The tumoricidal effect of this antibody relies in part upon antibody-dependent cell-mediated cytotoxicity. This report provides observations on certain factors or circumstances which could have an impact on this aspect of the therapeutic approach. These include: (1) concurrent medications; (2) the composition (immunophenotype) of peritumoral lymphocytes and the generally limited numbers of intratumoral T-lymphocytes/natural killer (NK) cells, monocytes, and neutrophilic granulocytes; (3) the presence of circulating HER-2/neu antigens which might bind the exogenous antibody and lead to immune complex formation; (4) the variable co-expression in the tumor of cytokines known to downregulate NK cell function (ie, transforming growth factor-beta1 [TGF-beta1] and platelet-derived growth factor [PDGF]-AB); and (5) the tumoral and/or stromal immunoreactivity for angiotensin-converting enzyme, which forms a part of one of the pathways for the activation of latent TGF-beta1 and for the biosynthesis of PDGF-AB. These observations provide an immunologic perspective for the use of monoclonal antibody therapy in HER-2/neu protein-receptor-positive breast carcinoma and suggest a role for the clinical laboratory in identifying potential avenues for additional manipulations of the immune system in individual cases in order to enhance the therapeutic response. PMID:10945564

  17. Synchronous invasive ductal carcinoma and intravascular large B-cell lymphoma of the breast: a case report and review of the literature

    PubMed Central

    2014-01-01

    Primary breast lymphomas (PBLs) represent less than 1% of all breast malignancies. Intravascular large B-cell lymphoma (ILBCL) is a rare, aggressive form of extranodal lymphoma. Breast involvement has only been described in the literature once previously. ILBCL is characterized by the proliferation of tumour cells within the lumen of small vessels of involved organs, resulting in their eventual occlusion. Clinical features are often vague, diagnosis is difficult and delayed, and prognosis is usually poor. We report the first ever case of synchronous ILBCL and invasive ductal carcinoma (IDC) of the breast in a patient presenting with pyrexia of unknown origin and altered mental status who underwent modified radical mastectomy and subsequent chemotherapy, and review the literature regarding intravascular large B-cell lymphoma, PBLs and synchronous carcinomas and lymphomas of the breast. PMID:24708809

  18. TRAIL Death Receptor-4 Expression Positively Correlates With the Tumor Grade in Breast Cancer Patients With Invasive Ductal Carcinoma

    SciTech Connect

    Sanlioglu, Ahter D.; Korcum, Aylin F.; Pestereli, Elif; Erdogan, Gulgun; Karaveli, Seyda; Savas, Burhan; Griffith, Thomas S.; Sanlioglu, Salih V.

    2007-11-01

    Purpose: Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) selectively induces apoptosis in cancer cells but not in normal cells, and a number of clinical trials have recently been initiated to test the safety and antitumoral potential of TRAIL in cancer patients. Four different receptors have been identified to interact with TRAIL: two are death-inducing receptors (TRAIL-R1 [DR4] and TRAIL-R2 [DR5]), whereas the other two (TRAIL-R3 [DcR1] and TRAIL-R4 [DcR2]) do not induce death upon ligation and are believed to counteract TRAIL-induced cytotoxicity. Because high levels of DcR2 expression have recently been correlated with carcinogenesis in the prostate and lung, this study investigated the importance of TRAIL and TRAIL receptor expression in breast cancer patients with invasive ductal carcinoma, taking various prognostic markers into consideration. Methods and Materials: Immunohistochemical analyses were performed on 90 breast cancer patients with invasive ductal carcinoma using TRAIL and TRAIL receptor-specific antibodies. Age, menopausal status, tumor size, lymph node status, tumor grade, lymphovascular invasion, perineural invasion, extracapsular tumor extension, presence of an extensive intraductal component, multicentricity, estrogen and progesterone receptor status, and CerbB2 expression levels were analyzed with respect to TRAIL/TRAIL receptor expression patterns. Results: The highest TRAIL receptor expressed in patients with invasive ductal carcinoma was DR4. Although progesterone receptor-positive patients exhibited lower DR5 expression, CerbB2-positive tissues displayed higher levels of both DR5 and TRAIL expressions. Conclusions: DR4 expression positively correlates with the tumor grade in breast cancer patients with invasive ductal carcinoma.

  19. Clinicopathological Significance of Dual-Specificity Protein Phosphatase 4 Expression in Invasive Ductal Carcinoma of the Breast

    PubMed Central

    Kim, Hyunsung; Jang, Se Min; Ahn, Hyein; Sim, Jongmin; Yi, Kijong; Chung, Yumin; Han, Hulin; Rehman, Abdul; Chung, Min Sung; Jang, Kiseok

    2015-01-01

    Purpose Dual-specificity protein phosphatase 4 (DUSP4), also known as mitogen-activated protein kinase phosphatase (MKP) 2 is a member of the inducible nuclear MKP group. The role of DUSP4 in cancer development and progression appears to vary with the type of malignancy. The purpose of this study was to investigate DUSP4 expression in a case series of invasive ductal carcinoma of the breast. Methods We constructed tissue microarrays consisting of 16, 14, 47, and 266 cases of normal breast tissue, usual ductal hyperplasia, ductal carcinoma in situ, and invasive ductal carcinoma, respectively. DUSP4 expression was investigated by immunohistochemistry. Results Cytoplasmic DUSP4 expression was observed. DUSP4 was more frequently expressed in malignant than in benign cases (p=0.024). The mean DUSP4 expression score was significantly higher in malignant tumors than in benign lesions (p=0.019). DUSP4 expression was significantly correlated with a larger tumor size (>2 cm, p=0.015). There was no significant correlation between overall survival or disease-free survival and DUSP4 expression in all 266 patients. We evaluated the impact of DUSP4 expression on the survival of 120 patients with T1-stage tumors. Interestingly, Kaplan-Meier survival curves revealed that DUSP4 expression had a significant effect on both overall patient survival (p=0.034, log-rank test) and disease-free survival (p=0.045, log-rank test). In early T-stage breast cancer, DUSP4 expression was associated with a worse prognosis. Conclusion DUSP4 is frequently upregulated in breast malignancy, and may play an important role in cancer development and progression. In addition, it may be a marker of adverse prognosis, especially in patients with early T1-stage cancer. PMID:25834604

  20. Platinum Based Chemotherapy or Observation in Treating Patients With Residual Triple-Negative Basal-Like Breast Cancer Following Neoadjuvant Chemotherapy

    ClinicalTrials.gov

    2015-05-14

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

  1. Carboplatin and Paclitaxel With or Without Atezolizumab Before Surgery in Treating Patients With Newly Diagnosed, Stage II-III Triple-Negative Breast Cancer

    ClinicalTrials.gov

    2016-08-29

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

  2. 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

  3. Identification of four novel human genes amplified and overexpressed in breast carcinoma and localized to the q11-q21.3 region of chromosome 17

    SciTech Connect

    Tomasetto, C.; Regnier, C.; Basset, P.

    1995-08-10

    We have performed differential screening of a human metastatic lymph node cDNA library to identify genes possibly involved during breast cancer progression. We have identified four novel genes overexpressed in malignant tissues. They were all located between q11 and q21.3, a region known to contain the c-erbB-2 oncogene and the BRCA1 breast carcinomas, and overexpression of three of them was dependent on gene amplification in breast cancer cell lines. These findings further support the concept that human chromosome 17 specifically carries genes possibly involved in breast cancer progression. 61 refs., 3 figs., 4 tabs.

  4. Estradiol Exposure Differentially Alters Monolayer versus Microtissue MCF-7 Human Breast Carcinoma Cultures.

    PubMed

    Vantangoli, Marguerite M; Madnick, Samantha J; Wilson, Shelby; Boekelheide, Kim

    2016-01-01

    The development of three-dimensional (3D) cultures is increasing, as they are able to provide the utility of in vitro models and the strength of testing in physiologically relevant systems. When cultured in a scaffold-free agarose hydrogel system, MCF-7 human breast carcinoma cells organize and develop into microtissues that contain a luminal space, in stark contrast to the flat morphology of MCF-7 two-dimensional (2D) monolayer cultures. Following exposure to 1nM E2, expression of typical estrogen-responsive genes, including progesterone receptor (PGR), PDZ containing domain 1 (PDZK1) and amphiregulin (AREG) is increased in both 2D and 3D cultures. When examining expression of other genes, particularly those involved in cell adhesion, there were large changes in 3D MCF-7 microtissues, with little to no change observed in the MCF-7 monolayer cultures. Together, these results indicate that while the initial estrogen-regulated transcriptional targets respond similarly in 2D and 3D cultures, there are large differences in activation of other pathways related to cell-cell interactions. PMID:27379522

  5. PHENOTYPIC CHARACTERIZATION OF BREAST INVASIVE CARCINOMA VIA TRANSFERABLE TISSUE MORPHOMETRIC PATTERNS LEARNED FROM GLIOBLASTOMA MULTIFORME

    PubMed Central

    Han, Ju; Fontenay, Gerald V.; Wang, Yunfu; Mao, Jian-Hua; Chang, Hang

    2016-01-01

    Quantitative analysis of whole slide images (WSIs) in a large cohort may provide predictive models of clinical outcome. However, the performance of the existing techniques is hindered as a result of large technical variations (e.g., fixation, staining) and biological heterogeneities (e.g., cell type, cell state) that are always present in a large cohort. Although unsupervised feature learning provides a promising way in learning pertinent features without human intervention, its capability can be greatly limited due to the lack of well-curated examples. In this paper, we explored the transferability of knowledge acquired from a well-curated Glioblastoma Multiforme (GBM) dataset through its application to the representation and characterization of tissue histology from the Cancer Genome Atlas (TCGA) Breast Invasive Carcinoma (BRCA) cohort. Our experimental results reveals two major phenotypic subtypes with statistically significantly different survival curves. Further differential expression analysis of these two subtypes indicates enrichment of genes regulated by NF-kB in response to TNF and genes up-regulated in response to IFNG. PMID:27390615

  6. Clinicopathological characteristics of infiltrating lobular breast carcinoma in elderly women: Preliminary results

    PubMed Central

    RUIBAL, ALVARO; AGUIAR, PABLO; DEL CAMEN DEL RÍO, MARIA; MENÉNDEZ, PRIMITIVA; ARIAS, JOSÉ IGNACIO; HERRANZ, MICHEL

    2015-01-01

    This study was conducted to investigate the clinicopathological parameters in elderly women (aged >70 years) with infiltrating lobular carcinoma (ILC) of the breast and compare the results with those obtained from younger patients (aged 55–70 years). The study sample included a total of 46 women with ILCs, 10 aged >70 and 36 aged 55–70 years. The parameters analysed were tumor size, histological grade (HG), axillary lymph node involvement, distant metastasis and immunohistochemical expression of estrogen, progesterone and androgen receptors, Ki67, p53 and B cell lymphoma 2. Compared to women aged 55–70 years, ILCs in women aged >70 years were commonly of larger size (P=0.068) and were more frequently HG3 (P=0.024). There were no statistically significant differences in the other parameters analysed. Furthermore, we were unable to determine differences in cancer recurrence and mortality in the two patient subgroups during our follow-up. In conclusion, our preliminary results, based on the limited number of cases included in this study, indicate that i) ILCs in women aged >70 years tended to be larger compared to those in women aged 55–70 years and were more frequently of grade 3; and ii) there were no significant differences in terms of recurrence and mortality between the two patient subgroups during our follow-up. PMID:26807244

  7. Estradiol Exposure Differentially Alters Monolayer versus Microtissue MCF-7 Human Breast Carcinoma Cultures

    PubMed Central

    Madnick, Samantha J.; Wilson, Shelby; Boekelheide, Kim

    2016-01-01

    The development of three-dimensional (3D) cultures is increasing, as they are able to provide the utility of in vitro models and the strength of testing in physiologically relevant systems. When cultured in a scaffold-free agarose hydrogel system, MCF-7 human breast carcinoma cells organize and develop into microtissues that contain a luminal space, in stark contrast to the flat morphology of MCF-7 two-dimensional (2D) monolayer cultures. Following exposure to 1nM E2, expression of typical estrogen-responsive genes, including progesterone receptor (PGR), PDZ containing domain 1 (PDZK1) and amphiregulin (AREG) is increased in both 2D and 3D cultures. When examining expression of other genes, particularly those involved in cell adhesion, there were large changes in 3D MCF-7 microtissues, with little to no change observed in the MCF-7 monolayer cultures. Together, these results indicate that while the initial estrogen-regulated transcriptional targets respond similarly in 2D and 3D cultures, there are large differences in activation of other pathways related to cell-cell interactions. PMID:27379522

  8. Anchorage Independent Growth of Breast Carcinoma Cells is Mediated by Serum Exosomes

    PubMed Central

    Ochieng, Josiah; Pratap, Siddharth; Khatua, Atanu K.; Sakwe., Amos M.

    2009-01-01

    We hereby report studies that suggest a role for serum exosomes in the anchorage independent growth (AIG) of tumor cells. In AIG assays, fetal bovine serum is one of the critical ingredients. We therefore purified exosomes from fetal bovine serum and examined their potential to promote growth of breast carcinoma cells in soft agar and Matrigel after reconstituting them into growth medium (EEM). In all the assays, viable colonies were formed only in the presence of exosomes. Some of the exosomal proteins we identified, have been documented by others and could be considered exosomal markers. Labeled purified exosomes were up-taken by the tumor cells, a process that could be competed out with excess unlabeled vesicles. Our data also suggested that once endocytosed by a cell, the exosomes could be recycled back to the conditioned medium from where they can be up-taken by other cells. We also demonstrated that low concentrations of exosomes activate MAP kinases, suggesting a mechanism by which they maintain the growth of the tumor cells in soft agar. Taken together, our data demonstrate that serum exosomes form a growth promoting platform for AIG of tumor cells and may open a new vista into cancer cell growth in vivo. PMID:19327352

  9. Initiation of Metastatic Breast Carcinoma by Targeting of the Ductal Epithelium with Adenovirus-Cre: A Novel Transgenic Mouse Model of Breast Cancer

    PubMed Central

    Svoronos, Nikolaos; Tesone, Amelia J.; Stephen, Tom L.; Perales-Puchalt, Alfredo; Nguyen, Jenny; Zhang, Paul J.; Fiering, Steven N.; Tchou, Julia; Conejo-Garcia, Jose R.

    2014-01-01

    Breast cancer is a heterogeneous disease involving complex cellular interactions between the developing tumor and immune system, eventually resulting in exponential tumor growth and metastasis to distal tissues and the collapse of anti-tumor immunity. Many useful animal models exist to study breast cancer, but none completely recapitulate the disease progression that occurs in humans. In order to gain a better understanding of the cellular interactions that result in the formation of latent metastasis and decreased survival, we have generated an inducible transgenic mouse model of YFP-expressing ductal carcinoma that develops after sexual maturity in immune-competent mice and is driven by consistent, endocrine-independent oncogene expression. Activation of YFP, ablation of p53, and expression of an oncogenic form of K-ras was achieved by the delivery of an adenovirus expressing Cre-recombinase into the mammary duct of sexually mature, virgin female mice. Tumors begin to appear 6 weeks after the initiation of oncogenic events. After tumors become apparent, they progress slowly for approximately two weeks before they begin to grow exponentially. After 7-8 weeks post-adenovirus injection, vasculature is observed connecting the tumor mass to distal lymph nodes, with eventual lymphovascular invasion of YFP+ tumor cells to the distal axillary lymph nodes. Infiltrating leukocyte populations are similar to those found in human breast carcinomas, including the presence of αβ and γδ T cells, macrophages and MDSCs. This unique model will facilitate the study of cellular and immunological mechanisms involved in latent metastasis and dormancy in addition to being useful for designing novel immunotherapeutic interventions to treat invasive breast cancer. PMID:24748051

  10. Expression of the stromelysin-3 gene in fibroblastic cells of invasive carcinomas of the breast and other human tissues: a review.

    PubMed

    Basset, P; Wolf, C; Chambon, P

    1993-01-01

    Stromelysin-3 (ST3) is a putative new matrix metalloproteinase (MMP) which may play a role in the progression of human carcinomas, and exhibits unique structural and functional characteristics among the MMP family. The ST3 gene, which is generally not expressed at significant levels in benign breast tumors, has been found to be expressed in all invasive breast carcinomas tested so far. The gene is also expressed in some in situ breast carcinomas, which have a higher probability to become invasive. ST3 RNA and protein are specifically found in fibroblastic cells immediately surrounding the neoplastic cells, both in invasive and in situ breast carcinomas. The same expression pattern is observed in other types of human carcinomas, and the highest ST3 RNA levels are observed in tumors that exhibit high local invasiveness. The ST3 gene is also expressed in fibroblastic cells during the inflammatory phase of wound healing, which suggests that ST3 gene expression in stromal fibroblasts may be under the control of factors produced by inflammatory cells during wound healing, and by cancer cells during carcinoma progression. ST3 may thus represent a stroma-derived factor necessary for the progression of epithelial malignancies, and its manipulation may possibly be used to develop new anti-cancer agents. PMID:8435474

  11. ER-α36, a novel isoform of ER-α66, is commonly over-expressed in apocrine and adenoid cystic carcinomas of the breast

    PubMed Central

    Vranic, Semir; Gatalica, Zoran; Deng, Hao; Frkovic-Grazio, Snjezana; Lee, Lisa M J; Gurjeva, Olga; Wang, Zhao-Yi

    2012-01-01

    Background ER-α36 is a novel 36 kDa isoform of the full-length oestrogen receptor alpha (ER-α66). ER-α36 primarily localises to the cytoplasm and the plasma membrane, and responds to membrane-initiated oestrogen and antioestrogen signalling pathways. Aim To examine the expression of ER-α36 in apocrine and adenoid cystic carcinoma of the breast, both of which are consistently ER-α66 negative and currently lack effective targeted therapeutic options. Methods 19 pure apocrine carcinomas (17 invasive and two in-situ carcinomas) and 11 adenoid cystic carcinomas of the breast were evaluated for ER-α36 expression, along with expressions of ER-α66, progesterone receptor (PR) and androgen receptor (AR) using immunohistochemical methods. Results All pure apocrine carcinomas showed a characteristic steroid receptor expression profile (ER-α66 and PR negative, AR strongly positive). ER-α36 expression was detected in 18/19 pure apocrine carcinomas (94.7%, 95% CI 75.1 to 98.7) in predominantly membranous and cytoplasmic distribution. When positive, pure apocrine carcinomas uniformly (100% of cells) expressed ER-α36. All adenoid cystic carcinomas were uniformly negative for all three classic steroid receptors, but ER-α36 was detected in 8/11 cases (72.7%, 95% CI 42.8 to 90) with the similar sub-cellular pattern of expression as in the pure apocrine carcinomas. When positive, adenoid cystic carcinomas expressed ER-α36 in the majority of cells (average 76%). Conclusion ER-α36, a novel isoform of ER-α66, is frequently over-expressed in apocrine and adenoid cystic carcinomas of the breast. These results indicate a potential for a novel targeted treatment in these cancers. PMID:21045236

  12. Manganese Superoxide Dismutase Expression Regulates the Switch Between an Epithelial and a Mesenchymal-Like Phenotype in Breast Carcinoma

    PubMed Central

    Loo, Ser Yue; Hirpara, Jayshree L.; Pandey, Vijay; Tan, Tuan Zea; Yap, Celestial T.; Lobie, Peter E.; Thiery, Jean Paul; Goh, Boon Cher

    2016-01-01

    Abstract Aim: Epithelial–mesenchymal transition (EMT) is characterized by the acquisition of invasive fibroblast-like morphology by epithelial cells that are highly polarized. EMT is recognized as a crucial mechanism in cancer progression and metastasis. In this study, we sought to assess the involvement of manganese superoxide dismutase (MnSOD) during the switch between epithelial-like and mesenchymal-like phenotypes in breast carcinoma. Results: Analysis of breast carcinomas from The Cancer Genome Atlas database revealed strong positive correlation between tumors' EMT score and the expression of MnSOD. This positive correlation between MnSOD and EMT score was significant and consistent across all breast cancer subtypes. Similarly, a positive correlation of EMT score and MnSOD expression was observed in established cell lines derived from breast cancers exhibiting phenotypes ranging from the most epithelial to the most mesenchymal. Interestingly, using phenotypically distinct breast cancer cell lines, we provide evidence that constitutively high or induced expression of MnSOD promotes the EMT-like phenotype by way of a redox milieu predominantly driven by hydrogen peroxide (H2O2). Conversely, gene knockdown of MnSOD results in the reversal of EMT to a mesenchymal–epithelial transition (MET)-like program, which appears to be a function of superoxide (O2−•)-directed signaling. Innovation and Conclusion: These data underscore the involvement of MnSOD in regulating the switch between the EMT and MET-associated phenotype by influencing cellular redox environment via its effect on the intracellular ratio between O2−• and H2O2. Strategies to manipulate MnSOD expression and/or the cellular redox milieu vis-a-vis O2−•:H2O2 could have potential therapeutic implications. Antioxid. Redox Signal. 25, 283–299. PMID:27400860

  13. Survivin upregulation, dependent on leptin-EGFR-Notch1 axis, is essential for leptin induced migration of breast carcinoma cells

    PubMed Central

    Knight, Brandi B.; Oprea-Ilies, Gabriela M.; Nagalingam, Arumugam; Yang, Lily; Cohen, Cynthia; Saxena, Neeraj K.; Sharma, Dipali

    2012-01-01

    Obese breast cancer patients exhibit a higher risk for larger tumor burden and increased metastasis. Molecular effects of obesity on carcinogenesis are mediated by autocrine and paracrine effects of adipocytokine leptin. Leptin participates in tumor progression and metastasis of human breast. We show that leptin induces clonogenicity and migration potential of breast cancer cells. We found that survivin expression is induced in response to leptin. In this study, we examine the role and leptin-mediated regulation of survivin. Leptin treatment leads to survivin upregulation, due in part to the activation of Notch1 and release of transcriptionally active Notch1-intracellular-domain (NICD). ChIP analysis show that NICD gets recruited to survivin promoter at CSL-binding-site in response to leptin treatment. Inhibition of Notch1 activity inhibits leptin-induced survivin upregulation. Leptin-induced transactivation of EGFR is involved in leptin-mediated Notch1 and survivin upregulation showing a novel upstream role of leptin-EGFR-Notch1 axis. We further show that leptin-induced migration of breast cancer cells requires survivin, as overexpression of survivin further increases, whereas silencing survivin abrogates leptin-induced migration. Using a pharmacological approach to inhibit survivin, we show that 3-hydroxy-3-methylglutaryl-coenzyme-A-reductase inhibitors (HRIs), lovastatin, can effectively inhibit leptin-induced survivin expression and migration. Importantly, leptin increased breast tumor growth in nude mice. These data show a novel role for survivin in leptin-induced migration and put forth pharmacological survivin inhibition as a potential novel therapeutic target. This conclusion is supported by in vivo data showing overexpression of leptin and survivin in epithelial cells of high grade ductal carcinoma in situ and high grade invasive carcinoma. PMID:21555376

  14. On the 6A 1 ← 4T 1 luminescence of Fe 3+ in disordered nanocrystalline LiGa 5O 8 prepared by a combustion reaction

    NASA Astrophysics Data System (ADS)

    Riesen, Hans

    2008-08-01

    A combustion reaction yields nanocrystalline LiGa 5O 8 in the inverse-spinel phase ( Fd3 m) in contrast to previous attempts by quenching microcrystalline powders from 1350 °C. This follows from XRD, IR and luminescence spectra of Fe 3+ at 298, 78 and 2.5 K. The ordered phase is obtained by calcination at 900 °C of the combustion product. The Fe 3+ luminescence is assigned to the 6A 1(S) ← 4T 1(G) transition of ions in tetrahedral sites in both polymorphs; this is confirmed by the similar behaviour of the 4A 2(F) ← 4T 1(P) luminescence of Co 2+ upon the order-disorder transition. The variation of the luminescence spectra is explained in terms of inhomogeneity and the Td → C3 symmetry reduction.

  15. Sequence dependence of Alimta (LY231514, MTA) combined with doxorubicin in ZR-75-1 human breast carcinoma cells.

    PubMed

    Schultz, R M; Dempsey, J A

    2001-01-01

    Alimta is a new-generation antifolate with inhibitory activity against multiple enzymes, including thymidylate synthase, glycinamide ribonucleotide formyltransferase and dihydrofolate reductase. Alimta is undergoing broad phase II evaluation as a single agent, and preliminary results show responses in several tumor types, including breast carcinoma. Doxorubicin is often used in combination chemotherapy of breast cancer. Because the two drugs have mechanisms of action that might be complementary, we investigated a possible synergism between doxorubicin and Alimta on growth inhibition of ZR-75-1 human breast carcinoma cells. Cytostatic activity was evaluated using semi-automated MTT assays, and drug interactions were determined using CalcuSyn (Chou/Hayball) multiple drug effect analyses. The cells were exposed to Alimta or doxorubicin as single agents and combinations for 24 hours starting at the time of plating or for 72 hours starting 24 hours after plating with a total culture time of 96 hours. Preincubation with Alimta for 24 hours followed by exposure to doxorubicin for 72 hours resulted in highly synergistic activity, whereas the opposite sequence or simultaneous exposure produced mainly an additive response. DNA flow cytometry studies indicated that Alimta causes a build-up of cells near the G1/S interface after 24 hours of incubation. The data suggest that, to obtain maximal antitumor activity, Alimta should precede doxorubicin when the drugs are given in combination chemotherapy protocols. PMID:11848474

  16. Chromosome alterations in breast carcinomas: frequent involvement of DNA losses including chromosomes 4q and 21q.

    PubMed Central

    Schwendel, A.; Richard, F.; Langreck, H.; Kaufmann, O.; Lage, H.; Winzer, K. J.; Petersen, I.; Dietel, M.

    1998-01-01

    Comparative genomic hybridization was applied to map DNA gains and losses in 39 invasive ductal breast carcinomas. Frequent abnormalities included gains on chromosomal regions 1q, 8q, 11q12-13, 16p, 19, 20q and X as well as frequent losses on 1p, 5q, 6q, 9p, 11q, 13q and 16q. Furthermore, frequent losses on 4q (20 cases) and 21q (14 cases) were found for the first time in this tumour type. High copy number amplifications were observed at 8q12-24, 11q11-13 and 20q13-ter. Highly differentiated tumours were associated with gains on 1q and 11q12-13 along with losses on 1p21-22, 4q, 13q, 11q21-ter. Undifferentiated breast carcinomas were characterized by additional DNA imbalances, i.e. deletions of 5q13-23, all of chromosome 9, the centromeric part of chromosome 13 including band 13q14 and the overrepresentation of chromosome X. We speculate that these changes are associated with tumour progression of invasive ductal breast cancer. Images Figure 2 Figure 3 PMID:9743305

  17. Methanolic extract of Pereskia bleo (Kunth) DC. (Cactaceae) induces apoptosis in breast carcinoma, T47-D cell line.

    PubMed

    Tan, M L; Sulaiman, S F; Najimuddin, N; Samian, M R; Muhammad, T S Tengku

    2005-01-01

    Currently, breast cancer is the leading cause of cancer-related death in women. Therefore, there is an urgent need to develop alternative therapeutic measures against this deadly disease. Here, we report the cytotoxicity activity and the mechanism of cell death exhibited by the methanol extract prepared from Pereskia bleo (Kunth) DC. (Cactaceae) plant against human breast carcinoma cell line, T-47D. In vitro cytotoxicity screening of methanol extract of Pereskia bleo plant indicated the presence of cytotoxicity activity of the extract against T-47D cells with EC50 of 2.0 microg/ml. T-47D cell death elicited by the extract was found to be apoptotic in nature based a clear indication of DNA fragmentation which is a hallmark of apoptosis. In addition, ultrastructural analysis also revealed apoptotic characteristics (the presence of chromatin margination and apoptotic bodies) in the extract-treated cells. RT-PCR analysis showed the mRNA expression levels of c-myc, and caspase 3 were markedly increased in the cells treated with the plant extract. However, p53 expression was only slightly increased as compared to caspase 3 and c-myc. Thus, the results from this study strongly suggest that the methanol extract of Pereskia bleo may contain bioactive compound(s) that caused breast carcinoma, T-47D cell death by apoptosis mechanism via the activation of caspase-3 and c-myc pathways. PMID:15588681

  18. [A Case of Glycogen-Rich Clear Cell Carcinoma of the Breast with Extensive Intraductal Components and Micrometastases to the Axillary Lymph Node].

    PubMed

    Seki, Hirohito; Sasaki, Kenichi; Morinaga, Shojiro; Asanuma, Fumiki; Yanaihara, Hisashi; Kaneda, Munehisa; Suzuki, Keiichi; Ishii, Yoshiyuki; Kamiya, Noriki; Osaku, Masayoshi; Ikeda, Tadashi

    2016-02-01

    A 48-year-old woman had a left breast mass identified during routine breast cancer screening. The mammogram showed pleomorphic-segmental microcalcifications in the mediolateral-oblique view of the left breast. Ultrasonography showed a hypoechoic mass approximately 3.7 cm in diameter with multiple calcifications. Contrast-enhanced magnetic resonance imaging of the breast showed non-mass like enhancement of approximately 4 cm in diameter in the C area of the left breast. She was diagnosed with glycogen-rich clear cell carcinoma (GRCC) by ultrasound-guided vacuum-assisted biopsy. Nipplesparing mastectomy was performed along with sentinel lymph node biopsy. The intraoperative consultation suggested sentinel lymph node metastasis and we therefore performed axillary lymph node dissection. Pathological examination reported microinvasive carcinomas, 0.4 cm in maximum diameter, and extensive intraductal components, 5 cm in size. The tumor cells were stained on PAS staining, but the stains were digested with diastase. The cells were negative for adipophilin. GRCC was first reported by Hull et al. This is a rare type of breast carcinoma. There is no standard therapy for this disease or any data on the prognosis of breast cancer patients with GRCC. PMID:27067690

  19. Medullary breast carcinoma in an 18-year-old female: report on one case diagnosed on fine-needle cytology sample.

    PubMed

    Galzerano, Antonio; Rocco, Nicola; Accurso, Antonello; Ciancia, Giuseppe; Campanile, Anna Cipolletta; Caccavello, Ferdinando; Fulciniti, Franco

    2014-05-01

    Medullary breast carcinoma (MBC) is a rare epithelial malignancy of the breast accounting for about 1-7% of all breast carcinomas. It is characterized by well-defined borders, a syncytial/solid pattern of growth of high grade atypical cells showing no glandular differentiation and a massive diffuse lympho-plasmacytic peritumoral infiltrate. Despite the high-grade atypias characterizing this neoplasm, MBC has been reported to have a better prognosis when compared with the common infiltrating duct carcinoma. MBCs typically lack estrogen and progesterone receptor (ER and PgR) expression and have a low incidence of ERBB2 overexpression. Genetically, they are often associated with BRCA-1 oncogene mutations and TP53 alterations. While MBC generally occurs in middle-aged women, ranging from 45 to 52 years of age, we report the case of a 18-year-old female patient which was diagnosed by means of fine-needle cytology sample. PMID:23341107

  20. Outcomes After Breast Conservation Treatment With Radiation in Women With Prior Nonbreast Malignancy and Subsequent Invasive Breast Carcinoma

    SciTech Connect

    Nemani, Deepika; Vapiwala, Neha Hwang, W.-T.; Solin, Lawrence J.

    2009-03-15

    Purpose: Little information has been reported regarding outcomes after treatment for patients with early-stage invasive breast cancer and a prior nonbreast malignancy. This report analyzes the outcomes in patients with Stage I and II breast cancer after breast conservation treatment (BCT) with a prior nonbreast malignancy. Methods and Materials: The study cohort comprised 66 women with invasive breast cancer and a prior nonbreast malignancy. All patients were treated with breast conservation surgery followed by definitive breast irradiation between 1978 and 2003. Median ages at diagnosis of invasive breast cancer and prior malignancy were 57 and 50 years, respectively. The median interval between the prior malignancy and breast cancer was 7.0 years. Median and mean follow-up times after BCT were 5.3 and 7.0 years. Results: The 5-year and 10-year overall survival rates were 94% (95% confidence interval [CI], 82-98%) and 78% (95% CI, 59-89%), respectively. There were 4 patients (6%) with local failure and 10 patients (15%) with distant metastases. The 10-year rate of local failure rate was 5% (95% CI, 2-16%) and freedom from distant metastases was 78% (95% CI, 61-88%). No obvious differences in survival or local control were noted compared with the reported results in the literature for patients with invasive breast cancer alone. Conclusions: Both overall survival and local control at 5 and 10 years were comparable to rates observed in early-stage breast cancer patients without a prior malignancy. Prior nonbreast malignancy is not a contraindication to BCT, if the primary cancer is effectively controlled.

  1. Modulation of breast cancer cell viability by a cannabinoid receptor 2 agonist, JWH-015, is calcium dependent

    PubMed Central

    Hanlon, Katherine E; Lozano-Ondoua, Alysia N; Umaretiya, Puja J; Symons-Liguori, Ashley M; Chandramouli, Anupama; Moy, Jamie K; Kwass, William K; Mantyh, Patrick W; Nelson, Mark A; Vanderah, Todd W

    2016-01-01

    Introduction Cannabinoid compounds, both nonspecific as well as agonists selective for either cannabinoid receptor 1 (CB1) or cannabinoid receptor 2 (CB2), have been shown to modulate the tumor microenvironment by inducing apoptosis in tumor cells in several model systems. The mechanism of this modulation remains only partially delineated, and activity induced via the CB1 and CB2 receptors may be distinct despite significant sequence homology and structural similarity of ligands. Methods The CB2-selective agonist JWH-015 was used to investigate mechanisms downstream of CB2 activation in mouse and human breast cancer cell lines in vitro and in a murine mammary tumor model. Results JWH-015 treatment significantly reduced primary tumor burden and metastasis of luciferase-tagged murine mammary carcinoma 4T1 cells in immunocompetent mice in vivo. Furthermore, JWH-015 reduced the viability of murine 4T1 and human MCF7 mammary carcinoma cells in vitro by inducing apoptosis. JWH-015-mediated reduction of breast cancer cell viability was not dependent on Gαi signaling in vitro or modified by classical pharmacological blockade of CB1, GPR55, TRPV1, or TRPA1 receptors. JWH-015 effects were calcium dependent and induced changes in MAPK/ERK signaling. Conclusion The results of this work characterize the actions of a CB2-selective agonist on breast cancer cells in a syngeneic murine model representing how a clinical presentation of cancer progression and metastasis may be significantly modulated by a G-protein-coupled receptor. PMID:27186076

  2. Multi-Institutional Experience of Ductal Carcinoma In Situ in Black vs White Patients Treated With Breast-Conserving Surgery and Whole Breast Radiation Therapy

    SciTech Connect

    Nelson, Carl; Bai, Harrison; Neboori, Hanmanth; Takita, Cristiane; Motwani, Sabin; Wright, Jean L.; Hobeika, Georges; Haffty, Bruce G.; Jones, Tiffanie; Goyal, Sharad; Moran, Meena S.

    2012-11-01

    Purpose: Given the paucity of data on racial disparities in ductal carcinoma in situ (DCIS), the data from a multi-institutional cohort of DCIS patients treated with breast-conserving surgery and whole breast radiation therapy (RT) were analyzed to determine whether racial disparities or differences exist. Methods and Materials: A total of 533 white and 76 black DCIS patients from 3 university-based cancer centers were uniformly treated with breast-conserving surgery and RT. All patient data were collected and analyzed as a function of race. Results: The median follow-up was 5.2 years. No significant racial differences were seen in tumor size, age at diagnosis, estrogen receptor status, necrosis, or grade (all P>.05). Of the treatment parameters, the RT dose delivered, boost, positive margin rates, frequency of hormone receptor status assessment, and receipt of hormonal therapy for the 2 cohorts did not significantly differ (all P>.05). The local relapse-free survival was similar at 5 years (96.1% and 98.1%, P=.399) and 10 years (92.8% vs 95.8%, P=.360), with no significant overall survival difference at 10 years (94.0% vs 88.9%, P=.290) between the white and black patients, respectively. On multivariate analysis, race was not an independent predictor of local relapse-free survival or overall survival when accounting for age, grade, and margin status. Conclusion: In our large cohort of DCIS patients uniformly treated at 3 institutions with breast conservation without any apparent differences in treatment delivery parameters, we demonstrated that the clinical and pathologic features and local survival outcomes did not differ as a function of race. Our results suggest that when black patients with DCIS are appropriately selected for breast conservation and receive adjuvant RT without racial disparities in the treatment parameters, differences in the outcomes as a function of race do not exist.

  3. Update on the molecular profile of the MDA-MB-453 cell line as a model for apocrine breast carcinoma studies

    PubMed Central

    VRANIC, SEMIR; GATALICA, ZORAN; WANG, ZHAO-YI

    2011-01-01

    Apocrine carcinoma of the breast has recently been refined through gene expression profiling. Due to various pathological studies, we compared the results with the MDA-MB-453 breast cancer cell line, a proposed model for apocrine breast carcinoma. The MDA-MB-453 cell line is androgen receptor-positive and ‘triple-negative’ in respect to estrogen receptor-α, progesterone receptor and the Her-2/neu protein expression. Cytogenetic analysis of the cell line revealed a hypertriploid clone characterized by extensive numerical and structural abnormalities including loss of the 9p.21 locus (P16-INK4a gene), also evidenced by the lack of p16INK4A protein expression in Western blot analysis and immunocytochemistry assays. Gains of chromosomes 7 and 17 without underlying EGFR, HER-2/neu, and TOP2A gene amplification were also observed. A mutation in the K-RAS gene (Gly13Asp GGC>GAC) was identified in the cell line, which was not observed in the six patient samples of apocrine breast carcinomas examined. Similarly, constitutive activation of the MAPK/ERK signaling pathway and deregulation of cell cycle proteins (p16-/pRb-/cyclin D1+ phenotype) with exceedingly high proliferation observed in the MDA-MB-453 cell line were not found in the tissue samples. In conclusion, the MDA-MB-453 cell line shares certain features with apocrine breast carcinoma but differs from patient tissues with regard to various significant characteristics, limiting the value of this cell line as a model for human apocrine breast carcinoma investigations. In contrast to the cell line, EGFR-positive apocrine carcinomas do not harbor K-RAS gene mutations, rendering these tumors amenable to targeted therapy with EGFR inhibitors. PMID:22121396

  4. Prognostic significance of oncogenic markers in ductal carcinoma in situ of the breast: a clinicopathologic study.

    PubMed

    Altintas, Sevilay; Lambein, Kathleen; Huizing, Manon T; Braems, Geert; Asjoe, Fernando Tjin; Hellemans, Hilde; Van Marck, Eric; Weyler, Joost; Praet, Marleen; Van den Broecke, Rudy; Vermorken, Jan B; Tjalma, Wiebren A

    2009-01-01

    Ductal carcinoma in situ (DCIS) is a heterogeneous malignant condition of the breast with an excellent prognosis. Until recently mastectomy was the standard treatment. As the results of the National Surgical Adjuvant Breast and Bowel Project-17 trial and the introduction of the Van Nuys Prognostic Index (VNPI) less radical therapies are used. Objectives are to identify clinicopathologic and biologic factors that may predict outcome. Cases of DCIS diagnosed in two Belgian University Centers were included. Paraffin-embedded material and Hematoxylin and Eosin stained slides of DCIS cases were reviewed and tumor size, margin width, nuclear grade, and comedo necrosis were assessed. Molecular markers (estrogen receptor, progesterone receptor, HER1-4, Ki67, and c-myc) were assayed immunohistochemically. Applied treatment strategies were correlated with the prospective use of the VNPI score. Kaplan-Meier survival plots were generated with log-rank significance and multiple regression analysis was carried out using Cox proportional hazards regression analysis; 159 patients were included with a median age of 54 years (range 29-78); 141 had DCIS and 18 DCIS with microinvasion. The median time of follow-up was 54 months (range 5-253). Twenty-three patients developed a recurrence (14.5%). The median time to recurrence was 46 months (range 5-253). Before the introduction of the VNPI, 37.5% of the DCIS patients showed a recurrence while thereafter 6.7% recurred (p < 0.005). Two recurrences occurred in the VNPI group I (7.1%); seven in the VNPI group II (8.5%) (median time to recurrence 66.3 months) and 14 in the VNPI group III (28.5%) (median time to recurrence 40.2 months) (disease-free survival [DFS]: p < 0.05). A Cox proportional hazards regression analysis indicated that tumor size, margin width, pathologic class, and age were independent predictors of recurrence, but none of the studied molecular markers showed this. Overexpression of HER4 in the presence of HER3 was found

  5. Zinc presence in invasive ductal carcinoma of the breast and its correlation with oestrogen receptor status

    NASA Astrophysics Data System (ADS)

    Farquharson, M. J.; Al-Ebraheem, A.; Geraki, K.; Leek, R.; Jubb, A.; Harris, A. L.

    2009-07-01

    Zinc is known to play an important role in many cellular processes, and the levels of zinc are controlled by specific transporters from the ZIP (SLC39A) influx transporter group and the ZnT (SLC30A) efflux transporter group. The distribution of zinc was measured in 59 samples of invasive ductal carcinoma of breast using synchrotron radiation micro probe x-ray fluorescence facilities. The samples were formalin fixed paraffin embedded tissue micro arrays (TMAs) enabling a high throughput of samples and allowing us to correlate the distribution of trace metals with tumour cell distribution and, for the first time, important biological variables. The samples were divided into two classes, 34 oestrogen receptor positive (ER+ve) and 25 oestrogen receptor negative (ER-ve) based on quantitative immunohistochemistry assessment. The overall levels of zinc (i.e. in tumour and surrounding tissue) in the ER+ve samples were on average 60% higher than those in the ER-ve samples. The zinc levels were higher in the ER+ve tumour areas compared to the ER-ve tumour areas with the mean levels in the ER+ve samples being approximately 80% higher than the mean ER-ve levels. However, the non-tumour tissue regions of the samples contained on average the same levels of zinc in both types of breast cancers. The relative levels of zinc in tumour areas of the tissue were compared with levels in areas of non-tumour surrounding tissue. There was a significant increase in zinc in the tumour regions of the ER+ve samples compared to the surrounding regions (P < 0.001) and a non-significant increase in the ER-ve samples. When comparing the increase in zinc in the tumour regions expressed as a percentage of the surrounding non-tumour tissue zinc level in the same sample, a significant difference between the ER+ve and ER-ve samples was found (P < 0.01).

  6. Inhibition of colony formation in agarose of metastatic human breast carcinoma and melanoma cells by synthetic glycoamine analogs.

    PubMed

    Glinsky, G V; Mossine, V V; Price, J E; Bielenberg, D; Glinsky, V V; Ananthaswamy, H N; Feather, M S

    1996-05-01

    We studied the influence of 10 synthetic glycoamine analogs on colony formation in 0.3 and 0.9% agarose by metastatic human breast carcinoma (MDA-MB-435) and melanoma (TXM-13) cells. Nine synthetic analogs significantly inhibited the colony formation in 0.9% agarose of MDA-MB-435 human breast carcinoma cells; five compounds caused a 73-83% reduction of colony formation. Seven synthetic glycoamines caused a significant inhibition of colony formation in 0.9% agarose by TXM-13 melanoma cells with the inhibitory effect ranging from 71 to 87%. The 50% inhibition (I50) doses and relative activity rank of the compounds were similar for both breast carcinoma and melanoma cell lines. The murine B16 melanoma cell aggregation assay was employed to elucidate the potential mechanism(s) of the inhibitory activity of synthetic glycoamines. The relative activity ranks of the compounds based on the independently determined I50 doses for both cell aggregation and clonogenic growth assays were very similar for the four most active synthetic analogs and clearly indicated the importance of hydrophobic amino acid in mediating the bioactivity of synthetic glycoamines. In both experimental systems (clonogenic growth in agarose and cell aggregation assay) the leading compound was N-(1-deoxy-D-fructos-1-yl)-D-leucine (Fru-D-Leu) and the least active analog was N-(l-deoxy-D-fructos-1-yl)-glycine (Fru-Gly). These results show that synthetic glycoamines may act by competing for specific carbohydrate-lectin interactions, particularly those involving beta-galactoside-specific lectins expressed on metastatic cells. PMID:8674280

  7. The role of cytochromes p450 and aldo-keto reductases in prognosis of breast carcinoma patients.

    PubMed

    Hlaváč, Viktor; Brynychová, Veronika; Václavíková, Radka; Ehrlichová, Marie; Vrána, David; Pecha, Václav; Trnková, Markéta; Kodet, Roman; Mrhalová, Marcela; Kubáčková, Kateřina; Gatěk, Jiří; Vážan, Petr; Souček, Pavel

    2014-12-01

    Metabolism of anticancer drugs affects their antitumor effects. This study has investigated the associations of gene expression of enzymes metabolizing anticancer drugs with therapy response and survival of breast carcinoma patients. Gene expression of 13 aldo-keto reductases (AKRs), carbonyl reductase 1, and 10 cytochromes P450 (CYPs) was assessed using quantitative real-time polymerase chain reaction in tumors and paired adjacent nonneoplastic tissues from 68 posttreatment breast carcinoma patients. Eleven candidate genes were then evaluated in an independent series of 50 pretreatment patients. Protein expression of the most significant genes was confirmed by immunoblotting. AKR1A1 was significantly overexpressed and AKR1C1-4, KCNAB1, CYP2C19, CYP3A4, and CYP3A5 downregulated in tumors compared with control nonneoplastic tissues after correction for multiple testing. Significant association of CYP2B6 transcript levels in tumors with expression of hormonal receptors was found in the posttreatment set and replicated in the pretreatment set of patients. Significantly higher intratumoral levels of AKR1C1, AKR1C2, or CYP2W1 were found in responders to neoadjuvant chemotherapy compared with nonresponders. Patients with high AKR7A3 or CYP2B6 levels in the pretreatment set had significantly longer disease-free survival than patients with low levels. Protein products of AKR1C1, AKR1C2, AKR7A3, CYP3A4, and carbonyl reductase (CBR1) were found in tumors and those of AKR1C1, AKR7A3, and CBR1 correlated with their transcript levels. Small interfering RNA-directed knockdown of AKR1C2 or vector-mediated upregulation of CYP3A4 in MDA-MB-231 model cell line had no effect on cell proliferation after paclitaxel treatment in vitro. Prognostic and predictive roles of drug-metabolizing enzymes strikingly differ between posttreatment and pretreatment breast carcinoma patients. Mechanisms of action of AKR1C2, AKR7A3, CYP2B6, CYP3A4, and CBR1 should continue to be further followed in

  8. Study of the biological and prognostic significance of the antigen CaMBr8 on breast carcinoma.

    PubMed Central

    Facheris, P.; Perrone, F.; Ménard, S.; Andreola, S.; Bazzini, P.; Bufalino, R.; Canevari, S.; Cascinelli, N.; Colzani, E.; Di Fronzo, G.

    1992-01-01

    We previously reported that the expression on the primary tumour of the antigen CaMBr8 was related to a short survival, attributable either to higher tumour aggressiveness or a poor response to oophorectomy. To further verify the CaMBr8 prognostic value, we analysed retrospectively 862 breast cancer patients with a 19 year follow-up. In this series, CaMBr8 expression was found to be associated to some negative prognostic factors (premenopausal status, lymphnode invasion, a high number of mitosis and HER-2/neu oncoprotein expression), but had no influence on the patients' survival. Direct association with a poor prognosis was only evident in patients with lobular or mixed breast carcinoma, which however represent only a small fraction of the total breast cancers. Another possibility was that CaMBr8 could identify a subgroup of patients which did not respond to hormone therapy. To verify this hypothesis we evaluated on a second series of 116 patients the relationship between CaMBr8 expression and hormone-receptor levels. A negative association emerged which was also observed in vitro in the human breast cancer line MCF-7 treated with Sodium Butyrate, a differentiation inducer, which reduced hormone-receptor levels and increased CaMBr8 expression. In conclusion, the longer survival of CaMBr8 negative tumour patients observed in the initial study, was probably related to a better response to oophorectomy, due to the hormone-receptor level of their tumours. PMID:1558805

  9. Validation of an immunohistochemical signature predictive of 8-year outcome for patients with breast carcinoma.

    PubMed

    Charpin, Colette; Tavassoli, Fattaneh; Secq, Véronique; Giusiano, Sophie; Villeret, Julia; Garcia, Stéphane; Birnbaum, Daniel; Bonnier, Pascal; Lavaut, Marie-Noëlle; Boubli, Léon; Carcopino, Xavier; Iovanna, Juan

    2012-08-01

    We recently reported that standardized quantitative immunohistochemical (IHC) assays allowed prediction of an adverse outcome among 572 node negative (N-) patients with breast carcinoma (BrCa). To further validate our prior findings, we repeated the IHC stains including a second series of BrCa diagnosed at Yale University. Tissue microarrays (TMAs) of two cohorts of patients with BrCa (418 Marseille University and 303 Yale University) were respectively investigated for IHC expression of 15 markers (HIF-1α, PI3K, pAKT, pmTOR, moesin, P21, 4(E) BP-1, P27, Ker5-6, pMAPKAPK-2, SHARP2, claudin-1, ALDH, AF6 and CD24). Quantitative measurements of immunoprecipitates densitometry assessed with an image analyzer were correlated with 8-year patients' outcome and compared in the two cohorts. The best predictive signature consisted of a combination of five markers that included HIF-1α, PI3K, claudin-1, AF6 and pAKT in N- BrCa. This combination permitted an accurate prediction of outcome in 92.34% (386/418) of N- patients in the first set (Marseille) and 89.8% (158/176) in the second set (Yale). The close results in both cohorts confirmed the validity of this original IHC signature predictive of prognosis in node negative BrCa. This validation suggests that in clinical practice, it would be possible with standardized kits (i) to identify patients with poor prognosis at diagnosis time, particularly in the N- BrCa subset, who would require more aggressive adjuvant therapy and (ii) to avoid useless expensive therapies and their side effects in N- patients with favorable prognosis. PMID:22120430

  10. Cytosolic thymidine kinase is a specific histopathologic tumour marker for breast carcinomas.

    PubMed

    He, Qimin; Mao, Yongrong; Wu, Jainping; Decker, Catrine; Merza, Malik; Wang, Naining; Eriksson, Staffan; Castro, Juan; Skog, Sven

    2004-10-01

    Thymidine kinase 1 (TK1), an enzyme involved in the synthesis of precursors for DNA, and thus proliferation dependent, has been suggested as a good tumour marker. We have recently developed poly/monoclonal antibodies against TK1, which proved useful for diagnostics in both serum and immunohistochemistry of cancer patients. The anti-TK1 monoclonal antibodies (mAbs) 1D11 and 1E3 were characterized by Western blot, immunoprecipitation and flow cytometry. TK1 mAbs and Ki-67 mAb were then used for immunohistochemistry staining of tumour sections from 54 patients with ductal infiltrated breast carcinoma. Results showed the relative number of patients with positively stained tumours for TK1 (mAb 1D11) and for Ki-67 (mAb MIB-1) were 47 and 41%, respectively, significantly related (p=0.007). Combination of TK1 mAbs 1D11 and 1E3 increased this number to 56%, due to detection of a significantly higher number of patients with grade 2 tumours. Patients with stage II and grade 2 tumours showed significantly higher TK1 staining when compared to stage I and grade 1. Ki-67 staining was significantly higher in stage III and grade 3. The tumours only stained for TK1 represented higher stages and grades, while tumours staining only for Ki-67 were of lower stages and grades. Combining TK1 and Ki-67 increased the number of patients with positively stained tumours to 69%. In conclusion, TK1 is a reliable marker for identification of patients with grade 2 tumours. The highest number of patients with positively stained tumours were obtained when both TK1 and Ki-67 markers were used. PMID:15375544

  11. Cancer Signature Investigation: ERBB2 (HER2)-Activating Mutation and Amplification-Positive Breast Carcinoma Mimicking Lung Primary.

    PubMed

    Shih, Jennifer; Bashir, Babar; Gustafson, Karen S; Andrake, Mark; Dunbrack, Roland L; Goldstein, Lori J; Boumber, Yanis

    2015-08-01

    Next-generation sequencing of primary and metachronous metastatic cancer lesions may impact patient care. We present a case of relapsed metastatic breast cancer with a dominant pulmonary lesion originally identified as lung adenocarcinoma. A 72-year-old, never-smoker woman with a protracted cough was found to have a large lung mass and regional lymphadenopathy on a chest CT. Lung mass biopsy showed adenocarcinoma with focal TTF-1 (thyroid transcription factor 1) positivity, favoring a lung primary. In addition to stereotactic brain radiation for cerebral metastases, she was started on carboplatin/pemetrexed. As part of the workup, the tumor was analyzed by a 50-gene targeted mutation panel, which detected 3 somatic mutations: ERBB2 (HER2) D769H activating missense mutation, TP53 Y126 inactivating truncating mutation, and SMARCB1 R374Q missense mutation. Of note, the patient had a history of stage IIA triple-negative grade 3 invasive ductal carcinoma of the left breast 1.5 years ago and received neoadjuvant chemotherapy and adjuvant radiation, and underwent a lumpectomy. Further analysis of her primary breast tumor showed a mutational profile identical to that of the lung tumor. Fluorescence in situ hybridization revealed HER2 amplification in the lung tumor, with a HER2/CEP17 ratio of 3.9. The patient was diagnosed with recurrent HER2-positive metastatic breast carcinoma with a coexisting ERBB2 (HER2) activating mutation. Chemotherapy was adjusted to include dual HER2-targeted therapy containing trastuzumab and pertuzumab, resulting in an ongoing partial response. This case demonstrates that a unique genetic mutational profile can clarify whether a tumor represents a metastatic lesion or new malignancy when conventional morphological and immunohistochemical methods are indeterminate, and can directly impact treatment decisions. PMID:26285240

  12. Association between ALDH1+/CD133+ stem-like cells and tumor angiogenesis in invasive ductal breast carcinoma

    PubMed Central

    LV, XINQUAN; WANG, YINGZI; SONG, YIMIN; PANG, XIA; LI, HUIXIANG

    2016-01-01

    The growth and metastasis of tumors is dependent on angiogenesis; however, the association between tumor stem cells (TSCs) and tumor angiogenesis remains to be elucidated. The present study aimed to investigate the expression of the TSC markers aldehyde dehydrogenase 1 (ALDH1) and cluster of differentiation 133 (CD133) in invasive ductal breast carcinoma, and identify their correlation with tumor angiogenesis. Stem-like cells from the breast tissue of 120 patients, who were diagnosed with invasive ductal breast carcinoma at The First Affiliated Hospital of Zhengzhou University (Zhengzhou, Henan, China) between January 2009 and December 2010, were collec