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Sample records for breast tumor invasion

  1. Coexistence of Granular Cell Tumor and Invasive Ductal Breast Cancer in Contralateral Breasts: A Case Report

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    Maurizio Di Bonito

    2014-07-01

    Full Text Available Granular cell tumor (GCT is a benign tumor of the breast that can mimic, on breast imaging, invasive carcinomas. Biological evolution of mammary GCT is unknown, especially if it is associated with an invasive carcinoma in the same or contralateral breast. This report details the morphological features of these synchronous lesions highlighting their biological characteristics and suggesting an appropriate follow up.

  2. Tumor cell budding from focally disrupted tumor capsules: a common pathway for all breast cancer subtype derived invasion?

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    Yan-gao Man

    2010-01-01

    Full Text Available Human breast cancer represents a group of highly heterogeneous lesions consisting of about 20 morphologically and immnohistochemically distinct subtypes with substantially different prognoses. Our recent studies have suggested that all breast cancer subtypes, however, may share a common pathway, tumor cell budding from focally disrupted tumor capsules, for their invasion. The potential mechanisms and clinical implications of our observations are discussed.

  3. Clinicopathological study of rare invasive epithelial tumors of breast: An institutional study

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    Karthik Kasireddy

    2016-01-01

    Full Text Available Introduction: Invasive breast cancer (BC is the most common carcinoma in women. It accounts for 22% of all female cancers. Most tumors are derived from mammary duct epithelium, and up to 75% of BCs are ductal carcinomas. The second most common tumor is invasive lobular carcinoma. However, there are many variants which are less common but well defined by the World Health Organization classification. They comprise <10% of breast tumors. Their clinical behavior differs greatly. Hence, it is important to know their main histomorphological features to make the best treatment of choice and to foresee prognosis. Aims and Objectives: To study the histomorphological features, incidence, and clinical features of rare invasive epithelial tumors of the breast. Materials and Methods: This study was done in the department of pathology, Sri Devaraj Urs Medical College, Kolar. All the neoplastic breast lesions over a period of 5 years (July 2010-September 2015 are included in the study. Clinical features and other details (estrogen receptor/progesterone receptor, human epidermal receptor-2, lymph nodes are obtained from the department (surgery records. Specimens are received and preserved in 10% formalin and are subjected to routine histopathological processing. Hematoxylin and eosin sections are studied, and a morphological diagnosis is given. All rare invasive epithelial breast tumors will be reviewed meticulously. Results and Conclusion: A total number of invasive epithelial tumors of breast were 105. The most common presenting symptom was breast lump. Rare invasive epithelial breast tumors account to 28.5%. The age range from 15 to 70 years. Most common, rare invasive epithelial tumor in our study is medullary carcinoma. Hence, it is imperative to always maintain a Hawks vigil during microscopic diagnosis to know prognosis of the condition and to facilitate early and prompt treatment to the patient.

  4. The prognostic value of tumor budding in invasive breast cancer.

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    Liang, Fenli; Cao, Wei; Wang, Yili; Li, Linrui; Zhang, Guanjun; Wang, Zhuo

    2013-05-01

    We investigated the prognostic value of tumor budding in 160 cases of operable invasive ductal carcinoma, not otherwise specified (IDC-NOS). The number of buds was counted in H&E slides with a maximal invasive margin in a 0.950mm(2) field of vision (200×). According to a cut-off score selected by ROC analysis, the cohort was dichotomized into a low (0-7 budding foci, 107 cases, 66.9%) and a high-grade budding group (8 or more budding foci, 53 cases, 33.1%). The inter-observer test showed a good reproducibility with 0.717 as the К value. High-grade budding was significantly associated with the presence of lymphovascular invasion (LVI) (P=0.001), larger tumor size (P=0.014), and worse clinical outcome (Pbudded cells at the margin displayed epithelial mesenchymal transition (EMT)-like molecular phenotype and decreased proliferative activity. Survival analyses revealed that tumor budding (HR 4.275, Ptumor size (HR 2.468, P=0.002), node status (HR 2.362, Ptumor budding is a reproducible, significant, and independent histopathological prognostic factor in IDC-NOS. Copyright © 2013 Elsevier GmbH. All rights reserved.

  5. Epigenetic and genetic burden measures are associated with tumor characteristics in invasive breast carcinoma.

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    O'Sullivan, Dylan E; Johnson, Kevin C; Skinner, Lucy; Koestler, Devin C; Christensen, Brock C

    2016-05-03

    The development and progression of invasive breast cancer is characterized by alterations to the genome and epigenome. However, the relationship between breast tumor characteristics, disease subtypes, and patient outcomes with the cumulative burden of these molecular alterations are not well characterized. We determined the average departure of tumor DNA methylation from adjacent normal breast DNA methylation using Illumina 450K methylation data from 700 invasive breast tumors and 90 adjacent normal breast tissues in The Cancer Genome Atlas. From this we generated a novel summary measure of altered DNA methylation, the DNA methylation dysregulation index (MDI), and examined the relation of MDI with tumor characteristics and summary measures that quantify cumulative burden of genetic mutation and copy number alterations. Our analysis revealed that MDI was significantly associated with tumor stage (P = 0.017). Across invasive breast tumor subtypes we observed significant differences in genome-wide DNA MDIs (P = 4.9E-09) and in a fraction of the genome with copy number alterations (FGA) (P = 4.6E-03). Results from a linear regression adjusted for subject age, tumor stage, and estimated tumor purity indicated a positive significant association of MDI with both MCB and FGA (P = 0.036 and P epigenetic and genetic burden profile were associated with the PAM50 subtype and mutations in TP53, PIK3CA, and CDH1. Together, our work presents a novel framework for characterizing the epigenetic burden and adds to the understanding of the aggregate impact of epigenetic and genetic alterations in breast cancer.

  6. Coexistence of benign phyllodes tumor and invasive ductal carcinoma in distinct breasts: case report

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    Neto Guerino

    2012-04-01

    Full Text Available Abstract This report describes a rare case of coexistence of benign phyllodes tumor, which measured 9 cm in the right breast, and invasive ductal carcinoma of 6 cm in the left breast, synchronous and independent, in a 66-year-old patient. The patient underwent a bilateral mastectomy due to the size of both lesions. Such situations are rare and usually refer to the occurrence of ductal or lobular carcinoma in situ when associated with malignant phyllodes tumors, and more often in ipsilateral breast or intra-lesional.

  7. Toca-1 is suppressed by p53 to limit breast cancer cell invasion and tumor metastasis.

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    Chander, Harish; Brien, Colin D; Truesdell, Peter; Watt, Kathleen; Meens, Jalna; Schick, Colleen; Germain, Doris; Craig, Andrew W B

    2014-12-30

    Transducer of Cdc42-dependent actin assembly-1 (Toca-1) recruits actin regulatory proteins to invadopodia, and promotes breast tumor metastasis. Since metastatic breast tumors frequently harbor mutations in the tumor suppressor p53, we tested whether p53 regulates Toca-1 expression. Normal mammary epithelial cells (HBL-100, MCF10A) and breast cancer cell lines expressing wild-type (WT) p53 (DU4475, MTLn3) were treated with camptothecin or Nutlin-3 to stabilize p53 to test effects on Toca-1 mRNA and protein levels. Chromatin immunoprecipitation (ChIP) assays were performed to identify p53 binding site in Toca-1 gene. Stable silencing of p53 and Toca-1 were performed in MTLn3 cells to test effects on invadopodia and cell invasion in vitro, and tumor metastasis in vivo. We observed that breast cancer cell lines with mutant p53 have high levels of Toca-1 compared to those with WT p53. Stabilization of WT p53 led to further reduction in Toca-1 mRNA and protein levels in normal breast epithelial cells and breast cancer cells. ChIP assays revealed p53 binding within intron 2 of toca1, and reduced histone acetylation within its promoter region upon p53 upregulation or activation. Stable silencing of WT p53 in MTLn3 cells led to increased extracellular matrix degradation and cell invasion compared to control cells. Interestingly, the combined silencing of p53 and Toca-1 led to a partial rescue of these effects of p53 silencing in vitro and reduced lung metastases in mice. In human breast tumors, Toca-1 levels were high in subtypes with frequent p53 mutations, and high Toca-1 transcript levels correlated with increased risk of relapse. Based on these findings, we conclude that loss of p53 tumor suppressor function in breast cancers leads to upregulation of Toca-1, and results in enhanced risk of developing metastatic disease.

  8. Integrin-dependent response to laminin-511 regulates breast tumor cell invasion and metastasis.

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    Kusuma, Nicole; Denoyer, Delphine; Eble, Johannes A; Redvers, Richard P; Parker, Belinda S; Pelzer, Rebecca; Anderson, Robin L; Pouliot, Normand

    2012-02-01

    The basement membrane protein, laminin (LM)-511, is a potent adhesive and migratory substrate for metastatic breast tumor cells in vitro. Its expression correlates with tumor grade and metastatic potential in vivo. These observations suggest that responsiveness to autocrine or paracrine-derived LM-511 may be an important property regulating breast cancer metastasis in vivo. To address this, we compared the metastatic potential of 4T1 mammary carcinoma cells to that of 4T1 variants isolated by repeated chemotactic migration toward LM-511 in vitro (4T1LMF4) followed by serial injection into the mammary gland and recovery of spontaneous metastases from bone (4T1BM2). Variant subpopulations exhibited a distinct morphology on LM-511 and increased expression of β1 and β4 integrins compared to parental 4T1 cells. Importantly, mice inoculated with 4T1LMF4 and 4T1BM2 variants showed a 2.5- to 4-fold increase in the incidence of spontaneous metastasis to bone compared to 4T1 tumor-bearing mice. Functionally, 4T1BM2 variants were more adherent and more invasive toward LM-511 than parental 4T1 cells. Treatment of 4T1BM2 cells with lebein-1, a disintegrin with selectivity toward LM-type integrin receptors, potently inhibited their migration and invasion toward LM-511. Similarly, α3β1 integrin-dependent migration and invasion of human MDA-MB-231 breast carcinoma cells toward LM-511 were significantly inhibited by lebein-1. Taken together, these results provide strong evidence that LM-511 contributes to the metastasis of breast tumors and suggest that targeting integrin-LM-511 interactions with lebein-1 or other inhibitors of LM-511 receptors may have therapeutic potential for patients with advanced breast cancer. Copyright © 2011 UICC.

  9. Tumor-derived Matrix Metalloproteinase-13 (MMP-13) correlates with poor prognoses of invasive breast cancer

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    Zhang, Bin; Cao, Xuchen; Liu, Yanxue; Cao, Wenfeng; Zhang, Fei; Zhang, Shiwu; Li, Hongtao; Ning, Liansheng; Fu, Li; Niu, Yun; Niu, Ruifang; Sun, Baocun; Hao, Xishan

    2008-01-01

    Background Experimental evidence suggests that matrix metalloproteinase-13 (MMP-13) protein may promote breast tumor progression. However, its relevance to the progression of human breast cancer is yet to be established. Furthermore, it is not clear whether MMP-13 can be used as an independent breast cancer biomarker. This study was conducted to assess the expression profile of MMP-13 protein in invasive breast carcinomas to determine its diagnostic and prognostic significance, as well as its correlation with other biomarkers including estrogen receptor (ER), progesterone receptor (PR), Her-2/neu, MMP-2, MMP-9, tissue inhibitor of MMP-1 and -2 (TIMP-1 and TIMP-2). Methods Immunohistochemistry (IHC) was performed on paraffin-embedded tissue microarray containing specimens from 263 breast carcinomas. The intensity and the extent of IHC were scored by pathologists in blind fashion. The correlation of the gene expression profiles with patients' clinicopathological features and clinical outcomes were analyzed for statistical significance. Results MMP-13 protein was detected in the cytoplasm of the malignant cells and the peritumoral stromal cells. MMP-13 expression by tumor cells (p < 0.001) and stromal fibroblasts (p <0.001) both correlated with carcinoma infiltration of lymph nodes. MMP-13 also correlated with the expression of Her-2/neu (p = 0.015) and TIMP-1 (p < 0.010), respectively in tumor cells. Tumor-derived, but not stromal fibroblast-derived, MMP-13 correlated with aggressive tumor phenotypes. Moreover, high levels of MMP-13 expression were associated with decreased overall survival. In parallel, the prognostic value of MMP-13 expressed by peritumoral fibroblasts seems less significant. Our data suggest that lymph node status, tumor size, Her-2/neu expression, TIMP-1 and MMP-13 expression in cancer cells are independent prognostic factors. Conclusion Tumor-derived, but not stromal fibroblast-derived, MMP-13 correlated with aggressive tumor phenotypes, and

  10. Tiling array-CGH for the assessment of genomic similarities among synchronous unilateral and bilateral invasive breast cancer tumor pairs

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    Ringnér Markus

    2008-07-01

    Full Text Available Abstract Background Today, no objective criteria exist to differentiate between individual primary tumors and intra- or intermammary dissemination respectively, in patients diagnosed with two or more synchronous breast cancers. To elucidate whether these tumors most likely arise through clonal expansion, or whether they represent individual primary tumors is of tumor biological interest and may have clinical implications. In this respect, high resolution genomic profiling may provide a more reliable approach than conventional histopathological and tumor biological factors. Methods 32 K tiling microarray-based comparative genomic hybridization (aCGH was used to explore the genomic similarities among synchronous unilateral and bilateral invasive breast cancer tumor pairs, and was compared with histopathological and tumor biological parameters. Results Based on global copy number profiles and unsupervised hierarchical clustering, five of ten (p = 1.9 × 10-5 unilateral tumor pairs displayed similar genomic profiles within the pair, while only one of eight bilateral tumor pairs (p = 0.29 displayed pair-wise genomic similarities. DNA index, histological type and presence of vessel invasion correlated with the genomic analyses. Conclusion Synchronous unilateral tumor pairs are often genomically similar, while synchronous bilateral tumors most often represent individual primary tumors. However, two independent unilateral primary tumors can develop synchronously and contralateral tumor spread can occur. The presence of an intraductal component is not informative when establishing the independence of two tumors, while vessel invasion, the presence of which was found in clustering tumor pairs but not in tumor pairs that did not cluster together, supports the clustering outcome. Our data suggest that genomically similar unilateral tumor pairs may represent a more aggressive disease that requires the addition of more severe treatment modalities, and

  11. Confocal fluorescence microscopy for rapid evaluation of invasive tumor cellularity of inflammatory breast carcinoma core needle biopsies.

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    Dobbs, Jessica; Krishnamurthy, Savitri; Kyrish, Matthew; Benveniste, Ana Paula; Yang, Wei; Richards-Kortum, Rebecca

    2015-01-01

    Tissue sampling is a problematic issue for inflammatory breast carcinoma, and immediate evaluation following core needle biopsy is needed to evaluate specimen adequacy. We sought to determine if confocal fluorescence microscopy provides sufficient resolution to evaluate specimen adequacy by comparing invasive tumor cellularity estimated from standard histologic images to invasive tumor cellularity estimated from confocal images of breast core needle biopsy specimens. Grayscale confocal fluorescence images of breast core needle biopsy specimens were acquired following proflavine application. A breast-dedicated pathologist evaluated invasive tumor cellularity in histologic images with hematoxylin and eosin staining and in grayscale and false-colored confocal images of cores. Agreement between cellularity estimates was quantified using a kappa coefficient. 23 cores from 23 patients with suspected inflammatory breast carcinoma were imaged. Confocal images were acquired in an average of less than 2 min per core. Invasive tumor cellularity estimated from histologic and grayscale confocal images showed moderate agreement by kappa coefficient: κ = 0.48 ± 0.09 (p fluorescence microscopy can be performed immediately following specimen acquisition and could indicate the need for additional biopsies at the initial visit.

  12. [Synchronous and ipsilateral invasive ductal carcinoma of the breast occurring near a phyllodes tumor - a case report].

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    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.

  13. Lentivirus mediated RNA interference of EMMPRIN (CD147) gene inhibits the proliferation, matrigel invasion and tumor formation of breast cancer cells.

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    Yang, Jing; Wang, Rong; Li, Hongjiang; Lv, Qing; Meng, Wentong; Yang, Xiaoqin

    2016-07-08

    Overexpression of extracellular matrix metalloproteinase inducer (EMMPRIN) or cluster of differentiation 147 (CD147), a glycoprotein enriched on the plasma membrane of tumor cells, promotes proliferation, invasion, metastasis, and survival of malignant tumor cells. In this study, we sought to examine the expression of EMMPRIN in breast tumors, and to identify the potential roles of EMMPRIN on breast cancer cells. EMMPRIN expression in breast cancer tissues was assessed by immunohistochemistry. We used a lentivirus vector-based RNA interference (RNAi) approach expressing short hairpin RNA (shRNA) to knockdown EMMPRIN gene in breast cancer cell lines MDA-MB-231 and MCF-7. In vitro, Cell proliferative, invasive potential were determined by Cell Counting Kit (CCK-8), cell cycle analysis and matrigel invasion assay, respectively. In vivo, tumorigenicity was monitored by inoculating tumor cells into breast fat pad of female nude mice. EMMPRIN was over-expressed in breast tumors and breast cancer cell lines. Down-regulation of EMMPRIN by lentivirus vector-based RNAi led to decreased cell proliferative, decreased matrigel invasion in vitro, and attenuated tumor formation in vivo. High expression of EMMPRIN plays a crucial role in breast cancer cell proliferation, matrigel invasion and tumor formation.

  14. Correlation of primary tumor FDG uptake with clinicopathologic prognostic factors in invasive ductal carcinoma of the breast

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    Jo, I; Kim, Sung Hoon; Kim, Hae Won; Kang, Sung Hee [Keimyung University, School of Medicine, Daegu (Korea, Republic of); Zeon, Seok Kil [Dept. of Nuclear Medicine, Bundang Jesaeng General Hospital, Sungnam (Korea, Republic of); Kim, Su Jin [Dept. of Anesthesiology and Pain Medicine, Dongguk University, School of Medicine, Gyeongju (Korea, Republic of)

    2015-03-15

    The purpose of this study was to investigate the correlation of primary tumor FDG uptake to clinicopathological prognostic factors in invasive ductal carcinoma of the breast. We retrospectively reviewed 136 of 215 female patients with pathologically proven invasive ductal breast cancer from January 2008 to December 2011 who underwent F-18 FDG PET/CT for initial staging and follow-up after curative treatment with analysis of estrogen receptor (ER), progesterone receptor (PR) and human epithelial growth factor receptor 2 (HER2). The maximum standardized uptake value (SUV{sub max}) of the primary breast tumor was measured and compared with hormonal receptor and HER2 overexpression status. The high SUV{sub max} of primary breast tumors is significantly correlated with the clinicopathological factors: tumor size, histologic grade, TNM stage, negativity of ER, negativity of PR, HER2 overexpression and triple negativity. The recurrent group with non-triple negative cancer had a higher SUV{sub max} compared with the non-recurrent group, though no significant difference in FDG uptake was noted between the recurrence and non-recurrent groups in subjects with triple-negative cancer. Lymph node involvement was the independent risk factor for cancer recurrence in the multivariate analysis. In conclusion, high FDG uptake in primary breast tumors is significantly correlated with clinicopathological factors, such as tumor size, histologic grade, TNM stage, negativity of the hormonal receptor, HER2 overexpression and triple negativity. Therefore, FDG PET/CT is a helpful prognostic tool to direct the further management of patients with breast cancer.

  15. Induction of interleukin-1β by mouse mammary tumor irradiation promotes triple negative breast cancer cells invasion and metastasis development.

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    Bouchard, Gina; Therriault, Hélène; Bujold, Rachel; Saucier, Caroline; Paquette, Benoit

    2017-05-01

    Radiotherapy increases the level of inflammatory cytokines, some of which are known to promote metastasis. In a mouse model of triple negative breast cancer (TNBC), we determined whether irradiation of the mammary tumor increases the level of key cytokines and favors the development of lung metastases. D2A1 TNBC cells were implanted in the mammary glands of a Balb/c mouse and then 7 days old tumors were irradiated (4 × 6 Gy). The cytokines IL-1β, IL-4, IL-6, IL-10, IL-17 and MIP-2 were quantified in plasma before, midway and after irradiation. The effect of tumor irradiation on the invasion of cancer cells, the number of circulating tumor cells (CTC) and lung metastases were also measured. TNBC tumor irradiation significantly increased the plasma level of IL-1β, which was associated with a greater number of CTC (3.5-fold) and lung metastases (2.3-fold), compared to sham-irradiated animals. Enhancement of D2A1 cell invasion in mammary gland was associated with an increase of the matrix metalloproteinases-2 and -9 activity (MMP-2, -9). The ability of IL-1β to stimulate the invasiveness of irradiated D2A1 cells was confirmed by in vitro invasion chamber assays. Irradiation targeting a D2A1 tumor and its microenvironment increased the level of the inflammatory cytokine IL-1β and was associated with the promotion of cancer cell invasion and lung metastasis development.

  16. Malignant phyllodes tumor in the right breast and invasive lobular carcinoma within fibroadenoma in the other: case report

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    Luiz Henrique Gebrim

    2000-03-01

    Full Text Available CONTEXT: The malignant variety of the phyllodes tumor is rare. The occurrence of invasive lobular carcinoma within fibroadenoma is rare as well. DESIGN: Case report. CASE REPORT: A 58-year-old black female patient was referred to the Mastology unit of the Department of Gynecology, Federal University of São Paulo / Escola Paulista de Medicina, in February 1990, presenting an ulcerated tumor in the right breast with fast growth over the preceding six months. She was a virgin, with meno-pause at the age of 45 years and had not undergone hormone replacement treatment. The physical examination showed, in her right breast, an ulcerated tumor of 20 x 30 cm which was not adher-ent to the muscle level, multilobular and with fibroelastic consistency. The axillary lymph nodes were not palpable. The left breast showed a 2 x 3 cm painless, movable nodule, with well-defined edges, and fibroelastic consistency. We performed left-breast mammography, which showed several nodules with well-defined edges, the largest being 2 x 3 cm and exhibiting rough calcification and grouped microcalcifications within it. The patient underwent a frozen biopsy that showed a malignant variant of the phyllodes tumor in the right breast and fibroadenoma in the left one. After that, we performed a total mastectomy in the right breast and an excision biopsy in the left one. Paraffin study confirmed the frozen biopsy result from the right breast, yet we observed that in the interior of the fibroadenoma that was removed on the left, there was a focal area of invasive lobular carcinoma measuring 0.4 cm. The patient then underwent a modi-fied radical mastectomy with total axillary lymphadenectomy. None of the 21 dissected lymph nodes showed evidence of metastasis. In the follow-up, the patient evolved asymptomatically and with normal physical and laboratory examination results up to July 1997.

  17. Sentinel Lymph Node Biopsy and Isolated Tumor Cells in Invasive Lobular Versus Ductal Breast Cancer

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    Truin, Wilfred; Roumen, Rudi M.; Siesling, Sabine; van der Heiden-van der Loo, Margriet; Lobbezoo, Dorien J.; Tjan-Heijnen, Vivianne C.G.; Voogd, Adri C.

    2016-01-01

    Background Sentinel lymph node (SLN) biopsy is the standard of care for axillary staging in invasive breast cancer. The introduction of SLN biopsy with an extensive pathology examination, in addition to the introduction of the 2002 TNM classification, led to different axillary classification

  18. Non-invasive thermal IR detection of breast tumor development in vivo

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    Case, Jason R.; Young, Madison A.; Dréau, D.; Trammell, Susan R.

    2015-03-01

    Lumpectomy coupled with radiation therapy and/or chemotherapy comprises the treatment of breast cancer for many patients. We are developing an enhanced thermal IR imaging technique that can be used in real-time to guide tissue excision during a lumpectomy. This novel enhanced thermal imaging method is a combination of IR imaging (8- 10 μm) and selective heating of blood (~0.5 °C) relative to surrounding water-rich tissue using LED sources at low powers. Post-acquisition processing of these images highlights temporal changes in temperature and is sensitive to the presence of vascular structures. In this study, fluorescent and enhanced thermal imaging modalities were used to estimate breast cancer tumor volumes as a function of time in 19 murine subjects over a 30-day study period. Tumor volumes calculated from fluorescent imaging follow an exponential growth curve for the first 22 days of the study. Cell necrosis affected the tumor volume estimates based on the fluorescent images after Day 22. The tumor volumes estimated from enhanced thermal imaging show exponential growth over the entire study period. A strong correlation was found between tumor volumes estimated using fluorescent imaging and the enhanced IR images, indicating that enhanced thermal imaging is capable monitoring tumor growth. Further, the enhanced IR images reveal a corona of bright emission along the edges of the tumor masses. This novel IR technique could be used to estimate tumor margins in real-time during surgical procedures.

  19. In Situ Malignant Transformation and Progenitor-Mediated Cell Budding: Two Different Pathways for Breast Ductal and Lobular Tumor Invasion

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    Yan-gao Man, Mina Izadjoo, Guohong Song, Alexander Stojadinovic

    2011-01-01

    Full Text Available The human breast lobular and ductal structures and the derived tumors from these structures differ substantial in their morphology, microenvironment, biological presentation, functions, and clinical prognosis. Based on these differences, we have proposed that pre-invasive lobular tumors may progress to invasive lesions through “in situ malignant transformation”, in which the entire myoepithelial cell layer within a given lobule or lobular clusters undergoes extensive degeneration and disruptions, which allows the entire epithelial cell population associated with these myoepithelial cell layers directly invade the stroma or vascular structures. In contrast, pre-invasive ductal tumors may invade the stroma or vascular structures through “progenitor-mediated cell budding”, in which focal myoepithelial cell degeneration-induced aberrant leukocyte infiltration causes focal disruptions in the tumor capsules, which selectively favor monoclonal proliferation of the overlying tumor stem cells or a biologically more aggressive cell clone. Our current study attempted to provide more direct morphological and immunohistochemical data that are consistent with our hypotheses.

  20. Apparent diffusion coefficient in estrogen receptor-positive invasive ductal breast carcinoma: correlations with tumor-stroma ratio.

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    Ko, Eun Sook; Han, Boo-Kyung; Kim, Rock Bum; Cho, Eun Yoon; Ahn, Soomin; Nam, Seok Jin; Ko, Eun Young; Shin, Jung Hee; Hahn, Soo Yeon

    2014-04-01

    To determine whether apparent diffusion coefficient (ADC) values vary according to tumor-stroma ratio, dominant stroma type, or presence of central fibrosis in estrogen receptor-positive breast cancer. Institutional review board approval was obtained, and patient consent was waived. Sixty-one patients with estrogen receptor-positive invasive ductal carcinoma-not otherwise specified who underwent breast magnetic resonance (MR) imaging with diffusion-weighted (DW) imaging were included in this study. The ADC values of the lesions were measured. Two pathologists evaluated the tumor-stroma ratio, dominant stroma type (collagen, fibroblast, lymphocyte), and central fibrosis. Detectability on DW images was compared between the two groups according to the tumor-stroma ratio (stroma rich or stroma poor). Mean ADC values were retrospectively compared with the tumor-stroma ratio, dominant stroma type, and presence of a central fibrosis. Multiple linear regression analysis was performed to determine variables independently associated with ADC. On DW images, detectability was not significantly different between stroma-rich and stroma-poor groups (P = .244). ADC values were significantly lower in the stroma-poor group (P collagen-dominant type were lower than in fibroblast-dominant or lymphocyte-dominant types (P = .021). In multiple linear regression analysis, tumor-stroma ratio (P = .007), tumor size (P = .007), and dominant stroma type (collagen dominant, P = .029) were independently correlated with ADC. In estrogen receptor-positive breast cancers, ADC values showed significant differences according to the tumor-stroma ratio and dominant stroma type. RSNA, 2013

  1. Reliability of Prognostic and Predictive Factors Evaluated by Needle Core Biopsies of Large Breast Invasive Tumors.

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    Petrau, Camille; Clatot, Florian; Cornic, Marie; Berghian, Anca; Veresezan, Liana; Callonnec, Françoise; Baron, Marc; Veyret, Corinne; Laberge, Sophie; Thery, Jean-Christophe; Picquenot, Jean-Michel

    2015-10-01

    Preoperative biopsy of breast cancer allows for prognostic/predictive marker assessment. However, large tumors, which are the main candidates for preoperative chemotherapy, are potentially more heterogeneous than smaller ones, which questions the reliability of histologic analyses of needle core biopsy (NCB) specimens compared with whole surgical specimens (WSS). We studied the histologic concordance between NCB specimens and WSS in tumors larger than 2 cm. Early pT2 or higher breast cancers diagnosed between 2008 and 2011 in our center, with no preoperative treatments, were retrospectively screened. We assessed the main prognostic and predictive validated parameters. Comparisons were performed using the κ test. In total, 163 matched NCB specimens and WSS were analyzed. The correlation was excellent for ER and HER2 (κ = 0.94 and 0.91, respectively), moderate for PR (κ = 0.79) and histologic type (κ = 0.74), weak for Ki-67 (κ = 0.55), and minimal for SBR grade (κ = 0.29). Three of the 21 HER2-positive cases (14% of HER2-positive patients or 1.8% of all patients), by WSS analysis, were initially negative on NCB specimens even after chromogenic in situ hybridization. NCB for large breast tumors allowed reliable determination of ER/PR expression. However, the SBR grade may be deeply underestimated, and false-negative evaluation of the HER2 status would have led to a detrimental lack of trastuzumab administration. Copyright© by the American Society for Clinical Pathology.

  2. Accurate and reproducible invasive breast cancer detection in whole-slide images: A Deep Learning approach for quantifying tumor extent

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    Cruz-Roa, Angel; Gilmore, Hannah; Basavanhally, Ajay; Feldman, Michael; Ganesan, Shridar; Shih, Natalie N. C.; Tomaszewski, John; González, Fabio A.; Madabhushi, Anant

    2017-04-01

    With the increasing ability to routinely and rapidly digitize whole slide images with slide scanners, there has been interest in developing computerized image analysis algorithms for automated detection of disease extent from digital pathology images. The manual identification of presence and extent of breast cancer by a pathologist is critical for patient management for tumor staging and assessing treatment response. However, this process is tedious and subject to inter- and intra-reader variability. For computerized methods to be useful as decision support tools, they need to be resilient to data acquired from different sources, different staining and cutting protocols and different scanners. The objective of this study was to evaluate the accuracy and robustness of a deep learning-based method to automatically identify the extent of invasive tumor on digitized images. Here, we present a new method that employs a convolutional neural network for detecting presence of invasive tumor on whole slide images. Our approach involves training the classifier on nearly 400 exemplars from multiple different sites, and scanners, and then independently validating on almost 200 cases from The Cancer Genome Atlas. Our approach yielded a Dice coefficient of 75.86%, a positive predictive value of 71.62% and a negative predictive value of 96.77% in terms of pixel-by-pixel evaluation compared to manually annotated regions of invasive ductal carcinoma.

  3. Olive phenolics as c-Met inhibitors: (--Oleocanthal attenuates cell proliferation, invasiveness, and tumor growth in breast cancer models.

    Directory of Open Access Journals (Sweden)

    Mohamed R Akl

    Full Text Available Dysregulation of the Hepatocyte growth factor (HGF/c-Met signaling axis upregulates diverse tumor cell functions, including cell proliferation, survival, scattering and motility, epithelial-to-mesenchymal transition (EMT, angiogenesis, invasion, and metastasis. (--Oleocanthal is a naturally occurring secoiridoid from extra-virgin olive oil, which showed antiproliferative and antimigratory activity against different cancer cell lines. The aim of this study was to characterize the intracellular mechanisms involved in mediating the anticancer effects of (--oleocanthal treatment and the potential involvement of c-Met receptor signaling components in breast cancer. Results showed that (--oleocanthal inhibits the growth of human breast cancer cell lines MDA-MB-231, MCF-7 and BT-474 while similar treatment doses were found to have no effect on normal human MCF10A cell growth. In addition, (--oleocanthal treatment caused a dose-dependent inhibition of HGF-induced cell migration, invasion and G1/S cell cycle progression in breast cancer cell lines. Moreover, (--oleocanthal treatment effects were found to be mediated via inhibition of HGF-induced c-Met activation and its downstream mitogenic signaling pathways. This growth inhibitory effect is associated with blockade of EMT and reduction in cellular motility. Further results from in vivo studies showed that (--oleocanthal treatment suppressed tumor cell growth in an orthotopic model of breast cancer in athymic nude mice. Collectively, the findings of this study suggest that (--oleocanthal is a promising dietary supplement lead with potential for therapeutic use to control malignancies with aberrant c-Met activity.

  4. Nerve fibers infiltrate the tumor microenvironment and are associated with nerve growth factor production and lymph node invasion in breast cancer.

    Science.gov (United States)

    Pundavela, Jay; Roselli, Severine; Faulkner, Sam; Attia, John; Scott, Rodney J; Thorne, Rick F; Forbes, John F; Bradshaw, Ralph A; Walker, Marjorie M; Jobling, Phillip; Hondermarck, Hubert

    2015-10-01

    Infiltration of the tumor microenvironment by nerve fibers is an understudied aspect of breast carcinogenesis. In this study, the presence of nerve fibers was investigated in a cohort of 369 primary breast cancers (ductal carcinomas in situ, invasive ductal and lobular carcinomas) by immunohistochemistry for the neuronal marker PGP9.5. Isolated nerve fibers (axons) were detected in 28% of invasive ductal carcinomas as compared to only 12% of invasive lobular carcinomas and 8% of ductal carcinomas in situ (p = 0.0003). In invasive breast cancers, the presence of nerve fibers was observed in 15% of lymph node negative tumors and 28% of lymph node positive tumors (p = 0.0031), indicating a relationship with the metastatic potential. In addition, there was an association between the presence of nerve fibers and the expression of nerve growth factor (NGF) in cancer cells (p = 0.0001). In vitro, breast cancer cells were able to induce neurite outgrowth in PC12 cells, and this neurotrophic activity was partially inhibited by anti-NGF blocking antibodies. In conclusion, infiltration by nerve fibers is a feature of the tumor microenvironment that is associated with aggressiveness and involves NGF production by cancer cells. The potential participation of nerve fibers in breast cancer progression needs to be further considered. Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  5. Fibrotic focus: An important parameter for accurate prediction of a high level of tumor-associated macrophage infiltration in invasive ductal carcinoma of the breast.

    Science.gov (United States)

    Shimada, Hiroko; Hasebe, Takahiro; Sugiyama, Michiko; Shibasaki, Satomi; Sugitani, Ikuko; Ueda, Shigeto; Gotoh, Yoshiya; Yasuda, Masanori; Arai, Eiichi; Osaki, Akihiko; Saeki, Toshiaki

    2017-07-01

    Our group and others have previously reported that a fibrotic focus is a very useful histological factor for the accurate prediction of the outcome of patients with invasive ductal carcinoma of the breast. We classified 258 cases of invasive ductal carcinoma into those with and those without a fibrotic focus to investigate whether the presence of a fibrotic focus was significantly associated with the degree of tumor-associated macrophage (CD68, CD163 or CD204-positive) infiltration or whether the presence of tumor-associated macrophage infiltration heightened the malignant potential of invasive ductal carcinoma with a fibrotic focus. Multiple regression analyses demonstrated that a fibrotic focus was the only factor that was significantly associated with a high level of CD68-, CD163- or CD204-positive tumor-associated macrophage infiltration. The combined assessment of the presence or absence of a fibrotic focus and a high or a low level of CD204-positive tumor-associated macrophage infiltration clearly demonstrated that CD204-positive tumor-associated macrophage infiltration had a significant prognostic power only for patients with invasive ductal carcinoma with a fibrotic focus in multivariate analyses; CD204-positive tumor-associated macrophages might only exert a significant effect on tumor progression when a fibrotic focus is present within the invasive ductal carcinoma of the breast. © 2017 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.

  6. Contractility of the cell rear drives invasion of breast tumor cells in 3D Matrigel

    Science.gov (United States)

    Poincloux, Renaud; Collin, Olivier; Lizárraga, Floria; Romao, Maryse; Debray, Marcel; Piel, Matthieu; Chavrier, Philippe

    2011-01-01

    Cancer cells use different modes of migration, including integrin-dependent mesenchymal migration of elongated cells along elements of the 3D matrix as opposed to low-adhesion-, contraction-based amoeboid motility of rounded cells. We report that MDA-MB-231 human breast adenocarcinoma cells invade 3D Matrigel with a characteristic rounded morphology and with F-actin and myosin-IIa accumulating at the cell rear in a uropod-like structure. MDA-MB-231 cells display neither lamellipodia nor bleb extensions at the leading edge and do not require Arp2/3 complex activity for 3D invasion in Matrigel. Accumulation of phospho-MLC and blebbing activity were restricted to the uropod as reporters of actomyosin contractility, and velocimetric analysis of fluorescent beads embedded within the 3D matrix showed that pulling forces exerted to the matrix are restricted to the side and rear of cells. Inhibition of actomyosin contractility or β1 integrin function interferes with uropod formation, matrix deformation, and invasion through Matrigel. These findings support a model whereby actomyosin-based uropod contractility generates traction forces on the β1 integrin adhesion system to drive cell propulsion within the 3D matrix, with no contribution of lamellipodia extension or blebbing to movement. PMID:21245302

  7. Assessment of maturation status of tumor-infiltrating dendritic cells in invasive ductal carcinoma of the breast: relation with vascular endothelial growth factor expression.

    Science.gov (United States)

    El Deeb, Nevine M F; Mehanna, Radwa A

    2013-01-01

    Poor immunogenicity has been described in breast carcinoma although dendritic cells, the major antigen presenters, are known to infiltrate the tumor. Vascular endothelial growth factor has been proposed to reduce local immune response in tumors. We investigated the maturation status of dendritic cells in invasive ductal carcinoma of the breast in relation to vascular endothelial growth factor expression and clinicopathological parameters. Fifty invasive ductal carcinomas of the breast were immunostained with CD1a (marker of immature dendritic cells); CD83 (marker of mature dendritic cells), vascular endothelial growth factor, estrogen receptor and progesterone receptor. Mature dendritic cells were detected in 36 cases (72%), and correlated with smaller tumor size, negative lymph nodes, positive steroid receptor status, and lower grade (P cells were found in 100% of cases and correlated only with negative steroid receptor expression (estrogen receptor and progesterone receptor) (P=0.006 and 0.020 respectively). Vascular endothelial growth factor expression was detected in 44 cases (88%), and correlated directly with positive nodal metastases (P=0.014), correlated inversely with mature dendritic cell count (P=0.005); and did not correlate with immature dendritic cell count (P=0.104). Mature dendritic cell count correlates with good prognostic features in invasive ductal carcinoma of the breast, suggesting their role in initiating primary anti-tumor immune response. Vascular endothelial growth factor expression may play a role in inhibition of dendritic cell maturation sequence in the tumor microenvironment.

  8. Tumor initiating but differentiated luminal-like breast cancer cells are highly invasive in the absence of basal-like activity

    DEFF Research Database (Denmark)

    Kim, Jiyoung; Villadsen, René; Sørlie, Therese

    2012-01-01

    The majority of human breast cancers exhibit luminal epithelial differentiation. However, most aggressive behavior, including invasion and purported cancer stem cell activity, are considered characteristics of basal-like cells. We asked the following questions: Must luminal-like breast cancer cells...... become basal-like to initiate tumors or to invade? Could luminally differentiated cells within a basally initiated hierarchy also be tumorigenic? To answer these questions, we used rare and mutually exclusive lineage markers to isolate subsets of luminal-like and basal-like cells from human breast tumors....... We enriched for populations with or without prominent basal-like traits from individual tumors or single cell cloning from cell lines and recovered cells with a luminal-like phenotype. Tumor cells with basal-like traits mimicked phenotypic and functional behavior associated with stem cells assessed...

  9. CCN5/WISP-2 expression in breast adenocarcinoma is associated with less frequent progression of the disease and suppresses the invasive phenotypes of tumor cells.

    Science.gov (United States)

    Banerjee, Snigdha; Dhar, Gopal; Haque, Inamul; Kambhampati, Suman; Mehta, Smita; Sengupta, Krishanu; Tawfik, Ossama; Phillips, Teresa A; Banerjee, Sushanta K

    2008-09-15

    Although previous in vitro studies predicted that CCN5/WISP-2 may act as an anti-invasive gene in breast cancer, the distribution pattern of CCN5 in breast cancer samples is conflicting. Thus, we systematically investigated the CCN5 expression profile in noninvasive and invasive breast tumor samples and its functional relevance in breast cancer progression. The studies showed that CCN5 expression is biphasic, such that in normal samples CCN5 expression is undetectable, whereas its expression is markedly increased in noninvasive breast lesions, including atypical ductal hyperplasia and ductal carcinoma in situ. Further, CCN5 mRNA and protein levels are significantly reduced as the cancer progresses from a noninvasive to invasive type. Additionally, we showed that CCN5 mRNA and protein level was almost undetectable in poorly differentiated cancers compared with the moderately or well-differentiated samples and its expression inversely correlated with lymph node positivity. The result was further supported by evaluating the RNA expression profile in microdissected sections using real-time PCR analysis. Therefore, our data suggest a protective function of CCN5 in noninvasive breast tumor cells. This hypothesis was further supported by our in vitro studies illuminating that CCN5 is a negative regulator of migration and invasion of breast cancer cells, and these events could be regulated by CCN5 through the modulation of the expression of genes essential for an invasive front. These include Snail-E-cadherin signaling and matrix metalloproteinase (MMP)-9 and MMP-2. Collectively, these studies suggest that the protective effect of CCN5 in breast cancer progression may have important therapeutic implications.

  10. The NHERF1 PDZ2 domain regulates PKA-RhoA-p38-mediated NHE1 activation and invasion in breast tumor cells.

    Science.gov (United States)

    Cardone, Rosa A; Bellizzi, Antonia; Busco, Giovanni; Weinman, Edward J; Dell'Aquila, Maria E; Casavola, Valeria; Azzariti, Amalia; Mangia, Anita; Paradiso, Angelo; Reshkin, Stephan J

    2007-05-01

    Understanding the signal transduction systems governing invasion is fundamental for the design of therapeutic strategies against metastasis. Na(+)/H(+) exchanger regulatory factor (NHERF1) is a postsynaptic density 95/disc-large/zona occludens (PDZ) domain-containing protein that recruits membrane receptors/transporters and cytoplasmic signaling proteins into functional complexes. NHERF1 expression is altered in breast cancer, but its effective role in mammary carcinogenesis remains undefined. We report here that NHERF1 overexpression in human breast tumor biopsies is associated with metastatic progression, poor prognosis, and hypoxia-inducible factor-1alpha expression. In cultured tumor cells, hypoxia and serum deprivation increase NHERF1 expression, promote the formation of leading-edge pseudopodia, and redistribute NHERF1 to these pseudopodia. This pseudopodial localization of NHERF1 was verified in breast biopsies and in three-dimensional Matrigel culture. Furthermore, serum deprivation and hypoxia stimulate the Na(+)/H(+) exchanger, invasion, and activate a protein kinase A (PKA)-gated RhoA/p38 invasion signal module. Significantly, NHERF1 overexpression was sufficient to induce these morphological and functional changes, and it potentiated their induction by serum deprivation. Functional experiments with truncated and binding groove-mutated PDZ domain constructs demonstrated that NHERF1 regulates these processes through its PDZ2 domain. We conclude that NHERF1 overexpression enhances the invasive phenotype in breast cancer cells, both alone and in synergy with exposure to the tumor microenvironment, via the coordination of PKA-gated RhoA/p38 signaling.

  11. Assessment of Tumor Heterogeneity, as Evidenced by Gene Expression Profiles, Pathway Activation, and Gene Copy Number, in Patients with Multifocal Invasive Lobular Breast Tumors

    Science.gov (United States)

    Norton, Nadine; Advani, Pooja P.; Serie, Daniel J.; Geiger, Xochiquetzal J.; Necela, Brian M.; Axenfeld, Bianca C.; Kachergus, Jennifer M.; Feathers, Ryan W.; Carr, Jennifer M.; Crook, Julia E.; Moreno-Aspitia, Alvaro; Anastasiadis, Panos Z.; Perez, Edith A.; Thompson, E. Aubrey

    2016-01-01

    Background Invasive lobular carcinoma (ILC) comprises approximately ~10–20% of breast cancers. In general, multifocal/multicentric (MF/MC) breast cancer has been associated with an increased rate of regional lymph node metastases. Tumor heterogeneity between foci represents a largely unstudied source of genomic variation in those rare patients with MF/MC ILC. Methods We characterized gene expression and copy number in 2 or more foci from 11 patients with MF/MC ILC (all ER+, HER2-) and adjacent normal tissue. RNA and DNA were extracted from 3x1.5mm cores from all foci. Gene expression (730 genes) and copy number (80 genes) were measured using Nanostring PanCancer and Cancer CNV panels. Linear mixed models were employed to compare expression in tumor versus normal samples from the same patient, and to assess heterogeneity (variability) in expression among multiple ILC within an individual. Results 35 and 34 genes were upregulated (FC>2) and down-regulated (FC<0.5) respectively in ILC tumor relative to adjacent normal tissue, q<0.05. 9/34 down-regulated genes (FIGF, RELN, PROM1, SFRP1, MMP7, NTRK2, LAMB3, SPRY2, KIT) had changes larger than CDH1, a hallmark of ILC. Copy number changes in these patients were relatively few but consistent across foci within each patient. Amplification of three genes (CCND1, FADD, ORAOV1) at 11q13.3 was present in 2/11 patients in both foci. We observed significant evidence of within-patient between-foci variability (heterogeneity) in gene expression for 466 genes (p<0.05 with FDR 8%), including CDH1, FIGF, RELN, SFRP1, MMP7, NTRK2, LAMB3, SPRY2 and KIT. Conclusions There was substantial variation in gene expression between ILC foci within patients, including known markers of ILC, suggesting an additional level of complexity that should be addressed. PMID:27078887

  12. Malignant phyllodes breast tumor

    OpenAIRE

    Lisa R. Shah-Patel, MD

    2017-01-01

    Malignant phyllodes tumor is a rare tumor of the breast occurring in females usually between the ages of 35 and 55 years. It is often difficult to distinguish benign from malignant phyllodes tumors from other benign entities such as fibroadenomas. This case presentation demonstrates a woman with malignant phyllodes tumor treated with mastectomy with abdominal skin flap reconstruction.

  13. Malignant phyllodes breast tumor

    Directory of Open Access Journals (Sweden)

    Lisa R. Shah-Patel, MD

    2017-12-01

    Full Text Available Malignant phyllodes tumor is a rare tumor of the breast occurring in females usually between the ages of 35 and 55 years. It is often difficult to distinguish benign from malignant phyllodes tumors from other benign entities such as fibroadenomas. This case presentation demonstrates a woman with malignant phyllodes tumor treated with mastectomy with abdominal skin flap reconstruction.

  14. New Approaches for Early Detection of Breast Tumor Invasion or Progression

    Science.gov (United States)

    2004-08-01

    qua the tumor-free myometrial or endometrial tissues either close to or at a distance from pain, nausea, and anorexia that was unresponsive to steroid...cancer217 The requirement of epithelia for RA is thought to be met largely by RA generated in situ from micronutrient /prehormone retinol (vitamin A

  15. Direct-Conversion Molecular Breast Imaging of Invasive Breast Cancer: Imaging Features, Extent of Invasive Disease, and Comparison Between Invasive Ductal and Lobular Histology.

    Science.gov (United States)

    Conners, Amy Lynn; Jones, Katie N; Hruska, Carrie B; Geske, Jennifer R; Boughey, Judy C; Rhodes, Deborah J

    2015-09-01

    The purposes of this study were to compare the tumor appearance of invasive breast cancer on direct-conversion molecular breast imaging using a standardized lexicon and to determine how often direct-conversion molecular breast imaging identifies all known invasive tumor foci in the breast, and whether this differs for invasive ductal versus lobular histologic profiles. Patients with prior invasive breast cancer and concurrent direct-conversion molecular breast imaging examinations were retrospectively reviewed. Blinded review of direct-conversion molecular breast imaging examinations was performed by one of two radiologists, according to a validated lexicon. Direct-conversion molecular breast imaging findings were matched with lesions described on the pathology report to exclude benign reasons for direct-conversion molecular breast imaging findings and to document direct-conversion molecular breast imaging-occult tumor foci. Associations between direct-conversion molecular breast imaging findings and tumor histologic profiles were examined using chi-square tests. In 286 patients, 390 invasive tumor foci were present in 294 breasts. A corresponding direct-conversion molecular breast imaging finding was present for 341 of 390 (87%) tumor foci described on the pathology report. Invasive ductal carcinoma (IDC) tumor foci were more likely to be a mass (40% IDC vs 15% invasive lobular carcinoma [ILC]; p invasive disease in 79.8% of cases and was more likely to do so for IDC than for ILC (86.1% vs 56.7%; p invasive foci in 249 of 286 (87%) patients. Direct-conversion molecular breast imaging features of invasive cancer, including lesion type and intensity, differ by histologic subtype. Direct-conversion molecular breast imaging is less likely to show all foci of ILC compared with IDC.

  16. In situ localization of tumor cells associated with the epithelial-mesenchymal transition marker Snail and the prognostic impact of lymphocytes in the tumor microenvironment in invasive ductal breast cancer.

    Science.gov (United States)

    Alkatout, Ibrahim; Hübner, Friederike; Wenners, Antonia; Hedderich, Jürgen; Wiedermann, Meike; Sánchez, Cristina; Röcken, Christoph; Mathiak, Micaela; Maass, Nicolai; Klapper, Wolfram

    2017-04-01

    Tumor surgery is aimed at complete resection of the lesion while ensuring a sufficient tumor-specific safety distance. Nevertheless, in many cases the most peripheral part - the invasion front - remains in situ. Tumor cells at the tumor margin have been reported to lose their epithelial properties and acquire features of mesenchymal cells. The process of epithelial-to-mesenchymal transition (EMT) is believed to be of prime importance for tissue and vessel invasion. Furthermore, the detection of tumor-infiltrating lymphocytes in the microenvironment of breast cancer might serve as a reliable prognostic marker. We investigated tissue microarrays of 352 breast cancer patients with regard to the presence and distribution of the EMT factor Snail, and the presence of FoxP3, CD3 and CD8 in the immune microenvironment. The expression of the transcription factor Snail is strongly associated with longer disease-free and overall survival. The presence of CD3, CD8 or FoxP3 is associated with a better outcome, although statistically significant results were noted only for FoxP3. The prognostic significance of FoxP3 and Snail were also proven in multivariate analysis. Based on previous studies concerning the intratumoral heterogeneity of EMT, our results suggest that Snail and FoxP3 are possible prognostic markers for breast cancer. The diverse presence of lymphocytes in the tumor microenvironment (CD3 and CD8) was confirmed. Although the importance of these markers is known, their specific role in tumor invasion and metastasis as well as their hierarchical organization in these tumors remain unclear. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Prognostic value of primary tumor SUVmax on F-18 FDG PET/CT compared with semi-quantitative tumor uptake on Tc-99m sestamibi breast-specific gamma imaging in invasive ductal breast cancer.

    Science.gov (United States)

    Yoo, Jang; Yoon, Hai-Jeon; Kim, Bom Sahn

    2017-01-01

    This study aimed to evaluate the prognostic value of F-18 FDG PET/CT in comparison with Tc-99m sestamibi breast-specific gamma imaging (BSGI) and previously established clinical prognostic parameters of invasive ductal breast carcinoma (IDC). We retrospectively included 157 female IDC patients (mean age 49.2 years, range 29.9-78.9) who underwent PET/CT and BSGI. The maximum standardized uptake value (SUVmax) and tumor to normal background ratios (TNRs) of their primary tumors were measured on PET/CT and BSGI, respectively. Univariate and multivariate survival analyses were performed to evaluate the prognostic value of the measured parameters and other clinical prognostic factors: age, menopausal status, breast density, pathologic tumor size (pTS), axillary nodal status (ANS), nuclear grade, histologic grade, hormone receptor status of estrogen (ER) and progesterone receptors (PR) and HER-2 expression. Among 157 patients, recurrences occurred in 22 patients (14.0 %). In univariate analyses, pTS (p < 0.0001), ANS (p < 0.0001), nuclear grade (p = 0.0046), histologic grade (p = 0.0001), ER status (p < 0.0001), PR status (p = 0.0037), HER-2 status (p = 0.0007), primary tumor SUVmax (p < 0.0001) and TNR (p = 0.0001) were significant predictors of recurrence. Among them, pTS (p = 0.0172), ANS (p = 0.0416), ER status (p = 0.0375) and primary tumor SUVmax (p = 0.0239) were independent prognostic factors in multivariate regression analysis. High primary tumor SUVmax of PET/CT and high TNR of BSGI were poor prognostic factors in IDC patients; in addition, primary tumor SUVmax was an independent prognostic factor along with pTS, ANS and ER status.

  18. Breast cancer circulating tumor cells

    Directory of Open Access Journals (Sweden)

    Maria Joao Carvalho

    2011-12-01

    Full Text Available Metastasization of breast cancer involves various mechanisms responsible for progression from invasive lesion to dissemination in distant organs. Regional lymph node metastasization was considered an initial step in this process, but it is now recognized that hematogenous dissemination is a deviation from lymphatic circulation. The detection of circulating tumor cells (CTC is an aim in several oncology areas. For this purpose, several techniques have been used to detect CTC, including the use of antibodies and techniques with nucleic acids. This study reviews the published studies considering the detection of breast cancer CTC. There are focused the difficulties in identifying a CTC in a heterogeneous population, the handling of the sample, criteria of positivity, analytical techniques, and specific markers. There are systematized various specific markers of breast cancer cells also the problems with false positive results. Finally, we hypothesize clinical applications either as a prognostic marker or as a therapeutic response monitor.

  19. Synchronous Malignant Phyllodes Tumor with Skin Ulceration and Invasive Carcinoma as Collision Tumor.

    Science.gov (United States)

    Muthusamy, Rajeshwari K; Mehta, Sangita S

    2017-01-01

    Phyllodes tumor is a rare fibroepithelial biphasic tumor of the breast composed of hypercellular mesenchymal stroma and double-layered epithelial component, arranged in clefts with leaf-like projections. Phyllodes tumor with coincidental presence of invasive carcinoma or in situ ductal carcinoma in the same or distinct breast is a rare occurrence, documented by some reports. Invasive carcinoma can be seen within or outside the phyllodes tumor. Skin ulceration by malignant phyllodes tumor with coexisting invasive carcinoma as collision tumor is extremely rare. Here, we report an extremely rare presentation of malignant phyllodes tumor as a giant fungating mass with distinct invasive carcinoma in the same breast in a 51-year-old female.

  20. Collision tumor with inflammatory breast carcinoma and malignant phyllodes tumor: a case report and literature review.

    Science.gov (United States)

    Shin, Young Duck; Lee, Seul Kee; Kim, Kyu Sun; Park, Mi Ja; Kim, Joo Heon; Yim, Hyun Sun; Choi, Young Jin

    2014-01-08

    There have been some reports of coincidental presentation of breast carcinoma and phyllodes tumor in the same breast. Most of the cases were carcinoma that arose from a phyllodes tumor with a histologically identified transitional area, and they behaved less aggressively than the usually encountered carcinoma. Collision tumors are rare clinical entities in which two histologically distinct tumor types show involvement at the same site. The occurrence of these tumors in the breast is extremely rare. Here, we report a case of 45-year-old woman who had both invasive ductal carcinoma as the finding of inflammatory carcinoma and a malignant phyllodes tumor in the same breast. There was no evidence of a transitional area between the phyllodes tumor and the invasive ductal carcinoma. To our knowledge, this is the first report of a collision tumor of inflammatory breast carcinoma coincident with a malignant phyllodes tumor in same breast.

  1. Associations of Breast Cancer Risk Factors With Tumor Subtypes: A Pooled Analysis From the Breast Cancer Association Consortium Studies

    National Research Council Canada - National Science Library

    ...; Yang, Xiaohong R; Chang-Claude, Jenny; Goode, Ellen L; Couch, Fergus J; Nevanlinna, Heli; Milne, Roger L; Gaudet, Mia; Schmidt, Marjanka K; Broeks, Annegien; Cox, Angela; Fasching, Peter A; Hein, Rebecca; Spurdle, Amanda B; Blows, Fiona; ver, Kristy; Flesch-Janys, Dieter; Heinz, Judith; Sinn, Peter; Vrieling, Alina; Heikkinen, Tuomas; Aittomaeki, Kristiina; Heikkilae, Paeivi; Blomqvist, Carl; Lissowska, Jolanta; Peplonska, Beata; Chanock, Stephen; Figueroa, Jonine; Brinton, Louise; Hall, Per; Czene, Kamila; Humphreys, Keith; Darabi, Hatef; Liu, Jianjun; Van 't Veer, Laura J; Van Leeuwen, Flora E; Anulis, Irene L; Glendon, Gord; Knight, Julia A; Mulligan, Anna Marie; O'Malley, Frances P; Weerasooriya, Nayana; John, Esther M; Beckmann, Matthias W; Hartmann, Arndt; Weihbrecht, Sebastian B; Wachter, David L; Jud, Sebastian M. S; Loehberg, Christian R; Baglietto, Laura; English, Dallas R; Giles, Graham G; McLean, Catriona A; Severi, Gianluca; Lambrechts, Diether; Vandorpe, Thijs; Weltens, Caroline; Paridaens, Robert; Smeets, Ann; Neven, Patrick; Wildiers, Hans; Wang, Xianshu; Olson, Janet E; Cafourek, Victoria; Fredericksen, Zachary; Kosel, Matthew; Vachon, Celine; Cramp, Helen E; Connley, Daniel; Cross, Simon S; Balasubramanian, Sabapathy P; Reed, Malcolm W. R; Doerk, Thilo; Bremer, Michael; Meyer, Aneas; Karstens, Johann H; Ay, Aysun; Park-Simon, Tjoung-Won; Hillemanns, Peter; Arias Perez, Jose Ignacio; Menendez Roiguez, Primitiva; Zamora, Pilar; Bentez, Javier; Ko, Yon-Dschun; Fischer, Hans-Peter; Hamann, Ute; Pesch, Beate; Bruening, Thomas; Justenhoven, Christina; Brauch, Hiltrud; Eccles, Diana M; Tapper, William J; Gerty, Sue M; Sawyer, Elinor J; Tomlinson, Ian P; Jones, Angela; Kerin, Michael; Miller, Nicola; McInerney, Niall; Anton-Culver, Hoda; Ziogas, Argyrios

    2011-01-01

    ...) and progesterone receptor (PR) expression status of the tumors. Methods We pooled tumor marker and epidemiological risk factor data from 35 568 invasive breast cancer case patients from 34 studies participating in the Breast Cancer Association Consortium...

  2. A biophysical model of tumor invasion

    Science.gov (United States)

    Ganesan, Sashikumaar; Lingeshwaran, Shangerganesh

    2017-05-01

    Three-dimensional finite element computations of a cancer invasion model with nonlinear density-dependent diffusion and haptotactic sensitivity function are presented. The nonlinear model includes three key variables, namely the cancer cell density, the extra cellular matrix (ECM) density and the matrix degrading enzymes (MDE) concentration. In order to investigate the effects of tumor growth and invasion on a realistic geometry, the interactions between the cancer cells and the host tissue are incorporated into the model. The convergence study and the validation are first performed for the proposed numerical scheme. Then the effects of nonlinear diffusion and ECM-dependent haptotaxis on tumor growth and invasion in three-dimensional geometries are presented. Finally, several numerical simulations are performed with different combinations of nonlinear diffusion and haptotaxis functions to get an insight into the tumor invasion on a realistic (breast) geometry. The proposed computational model can be used to predict the location and shape of the tumor in realistic geometries at a particular instance.

  3. Invasive Breast Cancer Preferably and Predominantly Occurs at the Interface Between Fibroglandular and Adipose Tissue.

    Science.gov (United States)

    Zhu, Wenlian; Harvey, Susan; Macura, Katarzyna J; Euhus, David M; Artemov, Dmitri

    2017-02-01

    Increasing evidence suggests adipocyte involvement in malignant breast tumor invasive front or margin. The aim of this study was to evaluate the location of invasive breast tumors in relation to fibroglandular and adipose tissue by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Pretreatment breast DCE-MRI images of 294 patients with biopsy-proven invasive breast cancer from 2008 to 2014 were studied. Invasive breast tumors were visualized as enhanced lesions in the postcontrast subtraction images. Positive identification of biopsy-confirmed invasive breast tumors on DCE-MRI images was achieved by correlation of findings from breast MRI and pathology reports. Tumor location in relation to fibroglandular and adipose tissue was investigated using precontrast T1-weighted MRI images. Of 294 patients, 291 had DCE-MRI discernable invasive breast tumors located at the interface between fibroglandular and adipose tissues, regardless of the tumor size, type, receptor status, or breast composition. Invasive breast cancer preferably and predominantly occurs adjacent to breast adipose tissue. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Expression of Syk in invasive breast cancer: correlation to proliferation and invasiveness.

    Science.gov (United States)

    Repana, Katerina; Papazisis, Konstantinos; Foukas, Periklis; Valeri, Rozalia; Kortsaris, Alexandros; Deligiorgi, Eleni; Kyriakidis, Dimitrios

    2006-01-01

    Spleen tyrosine kinase (Syk) kinase has recently been considered as a tumor suppressor gene in breast cancer. Syk expression in patients with invasive breast cancer was immunohistochemically assessed. Decreased expression was found in 26% of the specimens examined. In cases with vascular invasion, expression of Syk was lost in the intravascular emboli. A significant relationship between increased proliferation levels (as estimated by the proliferative index, Ki67) and decreased Syk expression (p <0.05) was found. Our data suggest that Syk protein expression inversely correlates with the proliferation and invasive capacity of breast cancer.

  5. Regulation of in situ to invasive breast carcinoma transition

    Energy Technology Data Exchange (ETDEWEB)

    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.

  6. Regulation of In Situ to Invasive Breast CarcinomaTransition

    Energy Technology Data Exchange (ETDEWEB)

    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.

  7. 3D-CRT, Proton, or Brachytherapy APBI in Treating Patients With Invasive and Non-invasive Breast Cancer

    Science.gov (United States)

    2017-12-29

    Ductal Breast Carcinoma In Situ; Estrogen Receptor Positive; Grade 1 Invasive Breast Carcinoma; Grade 2 Invasive Breast Carcinoma; Grade 3 Invasive Breast Carcinoma; Invasive Ductal and Lobular Carcinoma In Situ; Mucinous Breast Carcinoma; Tubular Breast Carcinoma

  8. A human breast cell model of pre-invasive to invasive transition

    Energy Technology Data Exchange (ETDEWEB)

    Bissell, Mina J; Rizki, Aylin; Weaver, Valerie M.; Lee, Sun-Young; Rozenberg, Gabriela I.; Chin, Koei; Myers, Connie A.; Bascom, Jamie L.; Mott, Joni D.; Semeiks, Jeremy R.; Grate, Leslie R.; Mian, I. Saira; Borowsky, Alexander D.; Jensen, Roy A.; Idowu, Michael O.; Chen, Fanqing; Chen, David J.; Petersen, Ole W.; Gray, Joe W.; Bissell, Mina J.

    2008-03-10

    A crucial step in human breast cancer progression is the acquisition of invasiveness. There is a distinct lack of human cell culture models to study the transition from pre-invasive to invasive phenotype as it may occur 'spontaneously' in vivo. To delineate molecular alterations important for this transition, we isolated human breast epithelial cell lines that showed partial loss of tissue polarity in three-dimensional reconstituted-basement membrane cultures. These cells remained non-invasive; however, unlike their non-malignant counterparts, they exhibited a high propensity to acquire invasiveness through basement membrane in culture. The genomic aberrations and gene expression profiles of the cells in this model showed a high degree of similarity to primary breast tumor profiles. The xenograft tumors formed by the cell lines in three different microenvironments in nude mice displayed metaplastic phenotypes, including squamous and basal characteristics, with invasive cells exhibiting features of higher grade tumors. To find functionally significant changes in transition from pre-invasive to invasive phenotype, we performed attribute profile clustering analysis on the list of genes differentially expressed between pre-invasive and invasive cells. We found integral membrane proteins, transcription factors, kinases, transport molecules, and chemokines to be highly represented. In addition, expression of matrix metalloproteinases MMP-9,-13,-15,-17 was up regulated in the invasive cells. Using siRNA based approaches, we found these MMPs to be required for the invasive phenotype. This model provides a new tool for dissection of mechanisms by which pre-invasive breast cells could acquire invasiveness in a metaplastic context.

  9. Immunophenotyping invasive breast cancer: paving the road for molecular imaging.

    Science.gov (United States)

    Vermeulen, Jeroen F; van Brussel, Aram S A; van der Groep, Petra; Morsink, Folkert H M; Bult, Peter; van der Wall, Elsken; van Diest, Paul J

    2012-06-13

    Mammographic population screening in The Netherlands has increased the number of breast cancer patients with small and non-palpable breast tumors. Nevertheless, mammography is not ultimately sensitive and specific for distinct subtypes. Molecular imaging with targeted tracers might increase specificity and sensitivity of detection. Because development of new tracers is labor-intensive and costly, we searched for the smallest panel of tumor membrane markers that would allow detection of the wide spectrum of invasive breast cancers. Tissue microarrays containing 483 invasive breast cancers were stained by immunohistochemistry for a selected set of membrane proteins known to be expressed in breast cancer. The combination of highly tumor-specific markers glucose transporter 1 (GLUT1), epidermal growth factor receptor (EGFR), insulin-like growth factor-1 receptor (IGF1-R), human epidermal growth factor receptor 2 (HER2), hepatocyte growth factor receptor (MET), and carbonic anhydrase 9 (CAIX) 'detected' 45.5% of tumors, especially basal/triple negative and HER2-driven ductal cancers. Addition of markers with a 2-fold tumor-to-normal ratio increased the detection rate to 98%. Including only markers with >3 fold tumor-to-normal ratio (CD44v6) resulted in an 80% detection rate. The detection rate of the panel containing both tumor-specific and less tumor-specific markers was not dependent on age, tumor grade, tumor size, or lymph node status. In search of the minimal panel of targeted probes needed for the highest possible detection rate, we showed that 80% of all breast cancers express at least one of a panel of membrane markers (CD44v6, GLUT1, EGFR, HER2, and IGF1-R) that may therefore be suitable for molecular imaging strategies. This study thereby serves as a starting point for further development of a set of antibody-based optical tracers with a high breast cancer detection rate.

  10. Immunophenotyping invasive breast cancer: paving the road for molecular imaging

    Directory of Open Access Journals (Sweden)

    Vermeulen Jeroen F

    2012-06-01

    Full Text Available Abstract Background Mammographic population screening in The Netherlands has increased the number of breast cancer patients with small and non-palpable breast tumors. Nevertheless, mammography is not ultimately sensitive and specific for distinct subtypes. Molecular imaging with targeted tracers might increase specificity and sensitivity of detection. Because development of new tracers is labor-intensive and costly, we searched for the smallest panel of tumor membrane markers that would allow detection of the wide spectrum of invasive breast cancers. Methods Tissue microarrays containing 483 invasive breast cancers were stained by immunohistochemistry for a selected set of membrane proteins known to be expressed in breast cancer. Results The combination of highly tumor-specific markers glucose transporter 1 (GLUT1, epidermal growth factor receptor (EGFR, insulin-like growth factor-1 receptor (IGF1-R, human epidermal growth factor receptor 2 (HER2, hepatocyte growth factor receptor (MET, and carbonic anhydrase 9 (CAIX 'detected' 45.5% of tumors, especially basal/triple negative and HER2-driven ductal cancers. Addition of markers with a 2-fold tumor-to-normal ratio increased the detection rate to 98%. Including only markers with >3 fold tumor-to-normal ratio (CD44v6 resulted in an 80% detection rate. The detection rate of the panel containing both tumor-specific and less tumor-specific markers was not dependent on age, tumor grade, tumor size, or lymph node status. Conclusions In search of the minimal panel of targeted probes needed for the highest possible detection rate, we showed that 80% of all breast cancers express at least one of a panel of membrane markers (CD44v6, GLUT1, EGFR, HER2, and IGF1-R that may therefore be suitable for molecular imaging strategies. This study thereby serves as a starting point for further development of a set of antibody-based optical tracers with a high breast cancer detection rate.

  11. Osteoprotegerin mediates tumor-promoting effects of Interleukin-1beta in breast cancer cells

    NARCIS (Netherlands)

    Chung, S.T.M. (Stephanie Tsang Mui); D. Geerts (Dirk); Roseman, K. (Kim); Renaud, A. (Ashleigh); Connelly, L. (Linda)

    2017-01-01

    markdownabstract__Background:__ It is widely recognized that inflammation promotes breast cancer invasion and metastasis. Given the complex nature of the breast tumor inflammatory microenvironment, much remains to be understood of the molecular mechanisms that govern these effects. We have

  12. Investigating the KLF4 Gene Expression as a New Molecular Marker in Breast Tumors

    Directory of Open Access Journals (Sweden)

    MA Hosseinpour Feizi

    2013-12-01

    Results: The results showed that: 1 KLF4 is over expressed in Breast tumors rather than adjacent normal tissues. 2 KLF4 is an oncogene in breast tumors (at least in IDC type. 3 The KLF4 expression levels are related significantly with nature of malignant breast tumors. Conclusion: Findings do not confirm KLF4 as a diagnostic marker in classification and identification of tumoral tissues from non-tumoral ones in breast, but we can use this marker to identify at least 50% of invasive Ductal Carcinoma in breast and utilize it as a potential predictive factor to demonstrate severity degree in various tumors.

  13. Tumor Heterogeneity in Breast Cancer

    Science.gov (United States)

    Turashvili, Gulisa; Brogi, Edi

    2017-01-01

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

  14. Phyllodes Tumors of the Breast

    Science.gov (United States)

    Abusalem, Osama Turki; Al-Masri, Anwar

    2011-01-01

    Objective: To study all patients with phyllodes tumors of the breast which were diagnosed at King Hussien Medical Center and Prince Rashid Military Hospital between the 1st of may 2002 till January 2009. Methods: A total of 26 patients diagnosed to have phylloedes tumors were retrieved from the hospital records. All cases were analyzed and assessed in two main categories: demographical characteristics and histopathological parameters. The demographical characteristics included: sex and age of the patients, and tumor size while the histopathological aspects were divided into three subgroups: Benign, Borderline and Malignant tumors with its stromal components characteristics. All the histopathological reports for specimens sent by surgeons were reviewed by 2 senior pathologists. Statistical analysis was done by using Chi square and P-Value. Results: All our patients were females; their age range between 17-67 years, the mean patient age at presentation was 39 years. Out of the 26 patients diagnosed to have phyllodes tumor, 6 had breast-conserving therapy and 20 women had mastectomy. The types of Phyllodes tumors include: A-Benign phyllodes tumors (15 cases), B-Borderline phyllodes (7cases) and C-malignant phyllodes (4 cases). With significant values of benign tumors occurrence (pphyllodes tumors of the breast. The greatest dimension of the tumors ranged from 1 to 15 cm, with a mean of 5 cm. Approximately 73.1% of tumors were less or equal to 5 cm in the greatest dimension and 26.9% >5 cm. The duration of symptoms varied from one month to ten year.s Six patients had painful swellings, whereas in twenty patients the pain was absent. Four patients had recurrent tumors; the distinctive features of those with recurrent tumors were the histological findings of stromal over growth and the presence of positive resection margin. In our series, we found that three patients of those with recurrence discovered to have stromal over growth. While one only had a previous positive

  15. Vasodilator-Stimulated Phosphoprotein (VASP) depletion from breast cancer MDA-MB-231 cells inhibits tumor spheroid invasion through downregulation of Migfilin, β-catenin and urokinase-plasminogen activator (uPA)

    Energy Technology Data Exchange (ETDEWEB)

    Gkretsi, Vasiliki; Stylianou, Andreas; Stylianopoulos, Triantafyllos, E-mail: tstylian@ucy.ac.cy

    2017-03-15

    A hallmark of cancer cells is their ability to invade surrounding tissues and form metastases. Cell-extracellular matrix (ECM)-adhesion proteins are crucial in metastasis, connecting tumor ECM with actin cytoskeleton thus enabling cells to respond to mechanical cues. Vasodilator-stimulated phosphoprotein (VASP) is an actin-polymerization regulator which interacts with cell-ECM adhesion protein Migfilin, and regulates cell migration. We compared VASP expression in MCF-7 and MDA-MB-231 breast cancer (BC) cells and found that more invasive MDA-MB-231 cells overexpress VASP. We then utilized a 3-dimensional (3D) approach to study metastasis in MDA-MB-231 cells using a system that considers mechanical forces exerted by the ECM. We prepared 3D collagen I gels of increasing concentration, imaged them by atomic force microscopy, and used them to either embed cells or tumor spheroids, in the presence or absence of VASP. We show, for the first time, that VASP silencing downregulated Migfilin, β-catenin and urokinase plasminogen activator both in 2D and 3D, suggesting a matrix-independent mechanism. Tumor spheroids lacking VASP demonstrated impaired invasion, indicating VASP’s involvement in metastasis, which was corroborated by Kaplan-Meier plotter showing high VASP expression to be associated with poor remission-free survival in lymph node-positive BC patients. Hence, VASP may be a novel BC metastasis biomarker. - Highlights: • More invasive MDA-MB-231 overexpress VASP compared to MCF-7 breast cancer cells. • We prepared 3D collagen I gels of increasing concentration and characterized them. • VASP silencing downregulated Migfilin, β-catenin and uPA both in 2D and 3D culture. • Tumor spheroids lacking VASP demonstrated impaired invasion. • Kaplan-Meier plotter shows association of high VASP expression with poor survival.

  16. Coexistence of malignant phyllodes tumor and her2-positive locally advanced breast cancer in distinct breasts: A case report.

    Science.gov (United States)

    Sato, Tomoi; Muto, Ichiro; Sakai, Takeshi

    2016-01-01

    Phyllodes tumor of the breast is a rare biphasic neoplasm, accounting for less than 1% of all breast tumors. Coexistence of phyllodes tumor and breast cancer in distinct breasts is extremely rare. A 47-year-old Japanese woman presented with bilateral breast lumps. A HER2-positive, unresectable invasive carcinoma in the right breast and fibroadenoma in the left were diagnosed via core needle biopsy. During chemotherapy with anti-HER2 therapy, the breast cancer shrank quickly, while the left breast lump suddenly enlarged. Under a diagnosis of malignant neoplasm of the breast, left mastectomy was performed. Malignant phyllodes tumor was diagnosed by postoperative histological examination and recurred in multiple areas as early as 2 months after surgery. Only 10 cases of coexisting phyllodes tumor and breast cancer in distinct breasts have been reported in the English literature. Phyllodes tumor associated with breast cancer in distinct breasts tends to be malignant. This is the first case of phyllodes tumor rapidly enlarging during anti-HER2 chemotherapy for locally advanced HER2-positive breast cancer. Even during effective treatment of advanced or recurrent breast cancer, attention should also be paid to the contralateral breast for the possible association of a second malignancy such as phyllodes tumor. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  17. The cell surface mucin podocalyxin regulates collective breast tumor budding.

    Science.gov (United States)

    Graves, Marcia L; Cipollone, Jane A; Austin, Pamela; Bell, Erin M; Nielsen, Julie S; Gilks, C Blake; McNagny, Kelly M; Roskelley, Calvin D

    2016-01-22

    Overexpression of the transmembrane sialomucin podocalyxin, which is known to play a role in lumen formation during polarized epithelial morphogenesis, is an independent indicator of poor prognosis in a number of epithelial cancers, including those that arise in the breast. Therefore, we set out to determine if podocalyxin plays a functional role in breast tumor progression. MCF-7 breast cancer cells, which express little endogenous podocalyxin, were stably transfected with wild type podocalyxin for forced overexpression. 4T1 mammary tumor cells, which express considerable endogenous podocalyxin, were retrovirally transduced with a short hairpin ribonucleic acid (shRNA) targeting podocalyxin for stable knockdown. In vitro, the effects of podocalyxin on collective cellular migration and invasion were assessed in two-dimensional monolayer and three-dimensional basement membrane/collagen gel culture, respectively. In vivo, local invasion was assessed after orthotopic transplantation in immunocompromised mice. Forced overexpression of podocalyxin caused cohesive clusters of epithelial MCF-7 breast tumor cells to bud off from the primary tumor and collectively invade the stroma of the mouse mammary gland in vivo. This budding was not associated with any obvious changes in histoarchitecture, matrix deposition or proliferation in the primary tumour. In vitro, podocalyxin overexpression induced a collective migration of MCF-7 tumor cells in two-dimensional (2-D) monolayer culture that was dependent on the activity of the actin scaffolding protein ezrin, a cytoplasmic binding partner of podocalyxin. In three-dimensional (3-D) culture, podocalyxin overexpression induced a collective budding and invasion that was dependent on actomyosin contractility. Interestingly, the collectively invasive cell aggregates often contained expanded microlumens that were also observed in vivo. Conversely, when endogenous podocalyxin was removed from highly metastatic, but cohesive, 4T1 mammary

  18. [Phyllodes breast tumors].

    Science.gov (United States)

    Zedníková, I; Černá, M; Hlaváčková, M; Hes, O

    2015-01-01

    Phyllodes tumour is a breast tumour occurring very rarely. It accounts for only in 1% of all cases of breast tumour. The diagnosis of phyllodes tumours can be difficult in consideration of the small number of cases. Treatment of phyllodes tumours is always surgical. In 2004-2013, we operated on twelve female patients with phyllodes tumours out of the total number of 1564 surgeries for breast tumours (0.8%) at the Department of Surgery at Teaching Hospital in Pilsen. We evaluated the age, the biological behaviour of the tumour depending on the tumour size and duration, the distant metastases, therapy and survival. The average age at the time of surgery was fifty years (2684), the duration of disease to the surgical solution ranged from one month to ten years. Tumour size was in the range of two to twenty-nine centimetres, tumours measuring less than five centimetres were always benign. Tumour excision for benign phyllodes tumour was performed seven times. Malignant phyllodes tumour was diagnosed five times with mastectomy performed in each case, and the axilla was exenterated in three cases where nodes were benign in each of them. In one case, mastectomy was followed by radiotherapy because the tumour reached the edge of the resected part; the other patients were only monitored. In two patients, tumour spreading into the lungs was diagnosed at five to ten months after breast surgery. One patient with generalized disease died, the other ones live with no local recurrence of this disease. Median survival is fifty-two months; the disease-free interval is fifty months. The results show that if phyllodes tumour is diagnosed in time, it is almost exclusively benign. If the case history is longer and the tumour is growing, the likelihood of malignancy increases. Surgical treatment is also sufficient in the case of malignant forms. The breast surgery does not need to be supplemented with exenteration of axilla.Key words: breast - phyllodes tumour.

  19. The thioredoxin system in breast cancer cell invasion and migration

    Directory of Open Access Journals (Sweden)

    Maneet Bhatia

    2016-08-01

    Full Text Available Metastasis is the most life threatening aspect of breast cancer. It is a multi-step process involving invasion and migration of primary tumor cells with a subsequent colonization of these cells at a secondary location. The aim of the present study was to investigate the role of thioredoxin (Trx1 in the invasion and migration of breast cancer cells and to assess the strength of the association between high levels of Trx1 and thioredoxin reductase (TrxR1 expression with breast cancer patient survival. Our results indicate that the expression of both Trx1 and TrxR1 are statistically significantly increased in breast cancer patient cells compared with paired normal breast tissue from the same patient. Over-expression of Trx1 in MDA-MB-231 breast cancer cell lines enhanced cell invasion in in vitro assays while expression of a redox inactive mutant form of Trx1 (designated 1SS or the antisense mRNA inhibited cell invasion. Addition of exogenous Trx1 also enhanced cell invasion, while addition of a specific monoclonal antibody that inhibits Trx1 redox function decreased cell invasion. Over-expression of intracellular Trx1 did not increase cell migration but expression of intracellular 1SS inhibited migration. Addition of exogenous Trx1 enhanced cell migration while 1SS had no effect. Treatment with auranofin inhibited TrxR activity, cell migration and clonogenic activity of MDA-MB-231 cells, while increasing reactive oxygen species (ROS levels. Analysis of 25 independent cohorts with 5910 patients showed that Trx1 and TrxR1 were both associated with a poor patient prognosis in terms of overall survival, distant metastasis free survival and disease free survival. Therefore, targeting the Trx system with auranofin or other specific inhibitors may provide improved breast cancer patient outcomes through inhibition of cancer invasion and migration.

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

    Science.gov (United States)

    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.

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

    DEFF Research Database (Denmark)

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

    2011-01-01

    Breast cancers demonstrate substantial biological, clinical and etiological heterogeneity. We investigated breast cancer risk associations of eight susceptibility loci identified in GWAS and two putative susceptibility loci in candidate genes in relation to specific breast tumor subtypes. Subtypes...... were defined by five markers (ER, PR, HER2, CK5/6, EGFR) and other pathological and clinical features. Analyses included up to 30 040 invasive breast cancer cases and 53 692 controls from 31 studies within the Breast Cancer Association Consortium. We confirmed previous reports of stronger associations......3803662 (16q12), rs889312 (5q11), rs3817198 (11p15) and rs13387042 (2q35); however, only two of them (16q12 and 2q35) were associated with tumors with the core basal phenotype (P ≤ 0.002). These analyses are consistent with different biological origins of breast cancers, and indicate that tumor...

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

    DEFF Research Database (Denmark)

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

    2011-01-01

    Breast cancers demonstrate substantial biological, clinical and etiological heterogeneity. We investigated breast cancer risk associations of eight susceptibility loci identified in GWAS and two putative susceptibility loci in candidate genes in relation to specific breast tumor subtypes. Subtypes...... were defined by five markers (ER, PR, HER2, CK5/6, EGFR) and other pathological and clinical features. Analyses included up to 30 040 invasive breast cancer cases and 53 692 controls from 31 studies within the Breast Cancer Association Consortium. We confirmed previous reports of stronger associations......3803662 (16q12), rs889312 (5q11), rs3817198 (11p15) and rs13387042 (2q35); however, only two of them (16q12 and 2q35) were associated with tumors with the core basal phenotype (P = 0.002). These analyses are consistent with different biological origins of breast cancers, and indicate that tumor...

  3. Associations of Breast Cancer Risk Factors With Tumor Subtypes : A Pooled Analysis From the Breast Cancer Association Consortium Studies

    NARCIS (Netherlands)

    Yang, Xiaohong R.; Chang-Claude, Jenny; Goode, Ellen L.; Couch, Fergus J.; Nevanlinna, Heli; Milne, Roger L.; Gaudet, Mia; Schmidt, Marjanka K.; Broeks, Annegien; Cox, Angela; Fasching, Peter A.; Hein, Rebecca; Spurdle, Amanda B.; Blows, Fiona; Driver, Kristy; Flesch-Janys, Dieter; Heinz, Judith; Sinn, Peter; Vrieling, Alina; Heikkinen, Tuomas; Aittomaeki, Kristiina; Heikkilae, Paeivi; Blomqvist, Carl; Lissowska, Jolanta; Peplonska, Beata; Chanock, Stephen; Figueroa, Jonine; Brinton, Louise; Hall, Per; Czene, Kamila; Humphreys, Keith; Darabi, Hatef; Liu, Jianjun; Van 't Veer, Laura J.; Van Leeuwen, Flora E.; Andrulis, Irene L.; Glendon, Gord; Knight, Julia A.; Mulligan, Anna Marie; O'Malley, Frances P.; Weerasooriya, Nayana; John, Esther M.; Beckmann, Matthias W.; Hartmann, Arndt; Weihbrecht, Sebastian B.; Wachter, David L.; Jud, Sebastian M. S.; Loehberg, Christian R.; Baglietto, Laura; English, Dallas R.; Giles, Graham G.; McLean, Catriona A.; Severi, Gianluca; Lambrechts, Diether; Vandorpe, Thijs; Weltens, Caroline; Paridaens, Robert; Smeets, Ann; Neven, Patrick; Wildiers, Hans; Wang, Xianshu; Olson, Janet E.; Cafourek, Victoria; Fredericksen, Zachary; Kosel, Matthew; Vachon, Celine; Cramp, Helen E.; Connley, Daniel; Cross, Simon S.; Balasubramanian, Sabapathy P.; Reed, Malcolm W. R.; Doerk, Thilo; Bremer, Michael; Meyer, Andreas; Karstens, Johann H.; Ay, Aysun; Park-Simon, Tjoung-Won; Hillemanns, Peter; Arias Perez, Jose Ignacio; Menendez Rodriguez, Primitiva; Zamora, Pilar; Bentez, Javier; Ko, Yon-Dschun; Fischer, Hans-Peter; Hamann, Ute; Pesch, Beate; Bruening, Thomas; Justenhoven, Christina; Brauch, Hiltrud; Eccles, Diana M.; Tapper, William J.; Gerty, Sue M.; Sawyer, Elinor J.; Tomlinson, Ian P.; Jones, Angela; Kerin, Michael; Miller, Nicola; McInerney, Niall; Anton-Culver, Hoda; Ziogas, Argyrios; Shen, Chen-Yang; Hsiung, Chia-Ni; Wu, Pei-Ei; Yang, Show-Lin; Yu, Jyh-Cherng; Chen, Shou-Tung; Hsu, Giu-Cheng; Haiman, Christopher A.; Henderson, Brian E.; Le Marchand, Loic; Kolonel, Laurence N.; Lindblom, Annika; Margolin, Sara; Jakubowska, Anna; Lubinski, Jan; Huzarski, Tomasz; Byrski, Tomasz; Gorski, Bohdan; Gronwald, Jacek; Hooning, Maartje J.; Hollestelle, Antoinette; van den Ouweland, Ans M. W.; Jager, Agnes; Kriege, Mieke; Tilanus-Linthorst, Madeleine M. A.; Collee, Margriet; Wang-Gohrke, Shan; Pylkaes, Katri; Jukkola-Vuorinen, Arja; Mononen, Kari; Grip, Mervi; Hirvikoski, Pasi; Winqvist, Robert; Mannermaa, Arto; Kosma, Veli-Matti; Kauppinen, Jaana; Kataja, Vesa; Auvinen, Paeivi; Soini, Ylermi; Sironen, Reijo; Bojesen, Stig E.; Orsted, David Dynnes; Kaur-Knudsen, Diljit; Flyger, Henrik; Nordestgaard, Borge G.; Holland, Helene; Chenevix-Trench, Georgia; Manoukian, Siranoush; Barile, Monica; Radice, Paolo; Hankinson, Susan E.; Hunter, David J.; Tamimi, Rulla; Sangrajrang, Suleeporn; Brennan, Paul; Mckay, James; Odefrey, Fabrice; Gaborieau, Valerie; Devilee, Peter; Huijts, P. E. A.; Tollenaar, R. A. E. M.; Seynaeve, C.; Dite, Gillian S.; Apicella, Carmel; Hopper, John L.; Hammet, Fleur; Tsimiklis, Helen; Smith, Letitia D.; Southey, Melissa C.; Humphreys, Manjeet K.; Easton, Douglas; Pharoah, Paul; Sherman, Mark E.; Garcia-Closas, Montserrat

    Background Previous studies have suggested that breast cancer risk factors are associated with estrogen receptor (ER) and progesterone receptor (PR) expression status of the tumors. Methods We pooled tumor marker and epidemiological risk factor data from 35 568 invasive breast cancer case patients

  4. Biomarker signatures of mitochondrial NDUFS3 in invasive breast carcinoma

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-09-09

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

  5. Chest wall tumors presenting as breast lumps.

    Science.gov (United States)

    Shousha, Sami; Sinnett, H Dudley

    2004-01-01

    Two recently seen patients presenting with large breast lumps that proved to be pure mesenchymal tumors arising from the underlying chest wall are presented. One tumor proved to be a giant cell tumor of soft tissue and the other an osteogenic sarcoma. It is suggested that these two cases may not be unique and that some mesenchymal breast tumors might have their origin in the chest wall. Breast computed tomography (CT) scans would help identify similar cases.

  6. Relationship between MMP-11 Expression in Invasive Ductal Breast Carcinoma with its Clinicopathologic Parameters

    Directory of Open Access Journals (Sweden)

    Farshad Naghshvar

    2017-04-01

    Full Text Available Background: Breast cancer is one of the most common cancers in the world, particularly in Iran. There are many genomic and molecular factors that cause the occurrence of breast cancer. Many markers are associated with tumor invasiveness. Matrix metalloproteinase includes a family of zinc-dependent endopeptidases that degrade various components of the extracellular matrix and basement membrane. Matrix metalloproteinase expressions increase in thyroid, colorectal, head and neck squamous cell carcinoma, lung, and ovarian cancers. It is correlated with tumor angiogenesis, invasion, and metastasis. Matrix metalloproteinase 11 is a member of the stromelysin subclass of the matrix metalloproteinase family. This enzyme is secreted to become a potentially active form against other matrix metalloproteinases. Contradictory results exist regarding the correlation between matrix metalloproteinase 11 expression and clinicopathologic parameters in breast cancer. Methods: This case-control study examined 80 invasive ductal carcinoma of the breast and 80 adjacent nonneoplastic breast tissue paraffin blocks to identify the relationship between matrix metalloproteinase 11 expression and clinicopathologic parameters such as age, tumor size, microscopic grade, perineural and vascular invasion, lymph node involvement, and stage by immunohistochemistry analyses Results: Among the 80 patients, 86.3% showed matrix metalloproteinase 11 expression in tumor cells and 17.5% had matrix metalloproteinase 11 expression in adjacent normal breast tissue. This expression correlated with stage, grade, lymph node metastasis, and perineural and vascular invasion (P0.05. Conclusion: Matrix metalloproteinase 11 expression is increased in breast cancer and may be used as a predictive factor for tumor invasiveness.

  7. A novel asymmetric 3D in-vitro assay for the study of tumor cell invasion

    Directory of Open Access Journals (Sweden)

    Neufeld Gera

    2009-11-01

    Full Text Available Abstract Background The induction of tumor cell invasion is an important step in tumor progression. Due to the cost and slowness of in-vivo invasion assays, there is need for quantitative in-vitro invasion assays that mimic as closely as possible the tumor environment and in which conditions can be rigorously controlled. Methods We have established a novel asymmetric 3D in-vitro invasion assay by embedding a monolayer of tumor cells between two layers of collagen. The cells were then allowed to invade the upper and lower layers of collagen. To visualize invading cells the gels were sectioned perpendicular to the monolayer so that after seeding the monolayer appears as a thin line precisely defining the origin of invasion. The number of invading tumor cells, their proliferation rate, the distance they traverse and the direction of invasion could then be determined quantitatively. Results The assay was used to compare the invasive properties of several tumor cell types and the results compare well with those obtained by previously described assays. Lysyl-oxidase like protein-2 (Loxl2 is a potent inducer of invasiveness. Using our assay we show for the first time that inhibition of endogenous Loxl2 expression in several types of tumor cells strongly inhibits their invasiveness. We also took advantage of the asymmetric nature of the assay in order to show that fibronectin enhances the invasiveness of breast cancer cells more potently than laminin. The asymmetric properties of the assay were also used to demonstrate that soluble factors derived from fibroblasts can preferentially attract invading breast cancer cells. Conclusion Our assay displays several advantages over previous invasion assays as it is allows the quantitative analysis of directional invasive behavior of tumor cells in a 3D environment mimicking the tumor microenvironment. It should be particularly useful for the study of the effects of components of the tumor microenvironment on

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

    Science.gov (United States)

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

    2011-09-09

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

  9. Phyllodes Tumor in a Lactating Breast

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    Murthy, Sudha S.; Raju, K. V. V. N.; Nair, Haripreetha G.

    2016-01-01

    Phyllodes tumor is attributed to a small fraction of primary tumors of the breast. Such tumors occur rarely in pregnancy and lactation. We report a case of a 25-year-old lactating mother presenting with a lump in the left breast. Core needle biopsy was opined as phyllodes tumor with lactational changes, and subsequent wide local excision confirmed the diagnosis of benign phyllodes tumor with lactational changes. The characteristic gross and microscopic findings of a well-circumscribed lesion ...

  10. Pathogenesis and progression of fibroepithelial breast tumors

    NARCIS (Netherlands)

    Kuijper, Arno

    2006-01-01

    Fibroadenoma and phyllodes tumor are fibroepithelial breast tumors. These tumors are biphasic, i.e. they are composed of stroma and epithelium. The behavior of fibroadenomas is benign, whereas phyllodes tumors can recur and even metastasize. Classification criteria for both tumors show considerable

  11. Perspectives of Nanotechnology in Minimally Invasive Therapy of Breast Cancer

    Directory of Open Access Journals (Sweden)

    Yamin Yang

    2013-01-01

    Full Text Available Breast cancer, the most common type of cancer among women in the western world, affects approximately one out of every eight women over their lifetime. In recognition of the high invasiveness of surgical excision and severe side effects of chemical and radiation therapies, increasing efforts are made to seek minimally invasive modalities with fewer side effects. Nanoparticles (<100 nm in size have shown promising capabilities for delivering targeted therapeutic drugs to cancer cells and confining the treatment mainly within tumors. Additionally, some nanoparticles exhibit distinct properties, such as conversion of photonic energy into heat, and these properties enable eradication of cancer cells. In this review, current utilization of nanostructures for cancer therapy, especially in minimally invasive therapy, is summarized with a particular interest in breast cancer.

  12. Invasive lobular carcinoma co-existing with benign phylloides tumor

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    S Shrestha

    2014-04-01

    Full Text Available Phylloides tumor constitutes less than 1% of all breast tumors and 2 - 3% of fibroepithelial breast tumors. Several histological parameters should be evaluated, including stromal cellularity, atypia, mitoses, stromal overgrowth, infiltrative borders, and presence or absence of necrosis. Here we report a case of a 60 years- old female who presented with left breast lump. Fine needle aspiration cytology was done which suggested epithelial hyperplasia with fibrocystic changes. Biopsy was performed which showed predominance of stromal hypercellularity with proliferation of spindle cells (no atypia, mitosis and stromal overgrowth were noticed. However, a focus showed proliferation of discohesive tumor cells arranged singly and in single file. A diagnosis of benign phylloides tumor with foci of invasive lobular carcinoma was made. The diagnosis was confirmed with IHC which showed intense 80%positivity for estrogen and progesterone receptor and spindle cells showing positivity for bcl-2. In situ lobular carcinoma component was not observed. DOI: http://dx.doi.org/10.3126/jpn.v4i7.10321   Journal of Pathology of Nepal (2014 Vol. 4, 597-599

  13. Invasive ductal carcinoma of the breast in a 14-year-old girl

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    Kim, Joo Yeon; Kim, Yun Ju; Kim, Sung Hun; Kang, Bong Joo [Seoul St. Mary' s Hospital, College of Medicine, The Catholic University of Korea, Department of Radiology, Seoul (Korea, Republic of); Song, Byung Joo [The Catholic University of Korea, Department of General Surgery, Seoul St. Mary' s Hospital, College of Medicine, Seoul (Korea, Republic of)

    2014-11-15

    Breast cancer is rare in children and adolescents. In particular, there are very few cases of invasive ductal carcinoma in childhood. We report a case of invasive ductal carcinoma of the breast in a 14-year-old girl presenting as a palpable mass. While the tumor demonstrated a relatively benign appearance on ultrasound, magnetic resonance imaging revealed typical malignant features. Several polymorphisms of single nucleotide variation were observed on gene analysis. The patient underwent breast conserving surgery and received subsequent concurrent chemo-radiation therapy. An awareness that ductal carcinoma of the breast rarely occurs in children is important to detect early stage breast cancer. (orig.)

  14. A model of tumor architecture and spatial interactions with tumor microenvironment in breast carcinoma

    Science.gov (United States)

    Ben Cheikh, Bassem; Bor-Angelier, Catherine; Racoceanu, Daniel

    2017-03-01

    Breast carcinomas are cancers that arise from the epithelial cells of the breast, which are the cells that line the lobules and the lactiferous ducts. Breast carcinoma is the most common type of breast cancer and can be divided into different subtypes based on architectural features and growth patterns, recognized during a histopathological examination. Tumor microenvironment (TME) is the cellular environment in which tumor cells develop. Being composed of various cell types having different biological roles, TME is recognized as playing an important role in the progression of the disease. The architectural heterogeneity in breast carcinomas and the spatial interactions with TME are, to date, not well understood. Developing a spatial model of tumor architecture and spatial interactions with TME can advance our understanding of tumor heterogeneity. Furthermore, generating histological synthetic datasets can contribute to validating, and comparing analytical methods that are used in digital pathology. In this work, we propose a modeling method that applies to different breast carcinoma subtypes and TME spatial distributions based on mathematical morphology. The model is based on a few morphological parameters that give access to a large spectrum of breast tumor architectures and are able to differentiate in-situ ductal carcinomas (DCIS) and histological subtypes of invasive carcinomas such as ductal (IDC) and lobular carcinoma (ILC). In addition, a part of the parameters of the model controls the spatial distribution of TME relative to the tumor. The validation of the model has been performed by comparing morphological features between real and simulated images.

  15. Modeling tumor invasion and metastasis in Drosophila

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    Wayne O. Miles

    2011-11-01

    Full Text Available Conservation of major signaling pathways between humans and flies has made Drosophila a useful model organism for cancer research. Our understanding of the mechanisms regulating cell growth, differentiation and development has been considerably advanced by studies in Drosophila. Several recent high profile studies have examined the processes constraining the metastatic growth of tumor cells in fruit fly models. Cell invasion can be studied in the context of an in vivo setting in flies, enabling the genetic requirements of the microenvironment of tumor cells undergoing metastasis to be analyzed. This Perspective discusses the strengths and limitations of Drosophila models of cancer invasion and the unique tools that have enabled these studies. It also highlights several recent reports that together make a strong case for Drosophila as a system with the potential for both testing novel concepts in tumor progression and cell invasion, and for uncovering players in metastasis.

  16. Breast-Cancer Tumor Size, Overdiagnosis, and Mammography Screening Effectiveness.

    Science.gov (United States)

    Welch, H Gilbert; Prorok, Philip C; O'Malley, A James; Kramer, Barnett S

    2016-10-13

    The goal of screening mammography is to detect small malignant tumors before they grow large enough to cause symptoms. Effective screening should therefore lead to the detection of a greater number of small tumors, followed by fewer large tumors over time. We used data from the Surveillance, Epidemiology, and End Results (SEER) program, 1975 through 2012, to calculate the tumor-size distribution and size-specific incidence of breast cancer among women 40 years of age or older. We then calculated the size-specific cancer case fatality rate for two time periods: a baseline period before the implementation of widespread screening mammography (1975 through 1979) and a period encompassing the most recent years for which 10 years of follow-up data were available (2000 through 2002). After the advent of screening mammography, the proportion of detected breast tumors that were small (invasive tumors measuring <2 cm or in situ carcinomas) increased from 36% to 68%; the proportion of detected tumors that were large (invasive tumors measuring ≥2 cm) decreased from 64% to 32%. However, this trend was less the result of a substantial decrease in the incidence of large tumors (with 30 fewer cases of cancer observed per 100,000 women in the period after the advent of screening than in the period before screening) and more the result of a substantial increase in the detection of small tumors (with 162 more cases of cancer observed per 100,000 women). Assuming that the underlying disease burden was stable, only 30 of the 162 additional small tumors per 100,000 women that were diagnosed were expected to progress to become large, which implied that the remaining 132 cases of cancer per 100,000 women were overdiagnosed (i.e., cases of cancer were detected on screening that never would have led to clinical symptoms). The potential of screening to lower breast cancer mortality is reflected in the declining incidence of larger tumors. However, with respect to only these large tumors

  17. Skin invasion and prognosis in node negative breast cancer: a retrospective study

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    Horii Rie

    2008-01-01

    Full Text Available Abstract Background The impact of skin invasion in node negative breast cancer is uncertain. Methods We determined the prognosis in 97 node negative breast cancer patients (case group who had tumors with skin invasion. Then we compared these patients with 4500 node negative invasive breast cancer patients treated surgically in the same period. Results Patients with skin invasion tended to be older, had more invasive lobular carcinoma and larger tumor size, and were less likely to have breast conserving surgery than those in the control group. The 5-year disease-free survival rate in the case group was 94.0%. There was no significant difference in the 10-year disease-specific overall survival rates in terms of skin invasion in node negative patients (90.7% in the case group, 92.9% in the control group; p = 0.2032. Conclusion Results suggest that skin invasion has no impact on survival in node negative invasive breast cancer patients. The adjuvant regimens which the individual institute applies for node negative breast cancer should be used regardless of skin invasion.

  18. Invasive Ductal Carcinoma Arising in Phyllodes Tumor With Isolated Tumor Cells in Sentinel Lymph Node

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    Ying-Ju Kuo

    2010-11-01

    Full Text Available Phyllodes tumor (PT consists of stroma of variable grading and benign ductal epithelium. Although exceptional, carcinomas that arise from the epithelium in PTs do exist, and seem to behave less aggressively than the usually encountered breast carcinoma. To the best of our knowledge, among the invasive carcinomas that have arisen in PTs, only 1 has been proved to have metastatic carcinoma in the lymph nodes. Here, we describe the youngest woman to have invasive ductal carcinoma that arose in a borderline PT, with isolated carcinoma cells in the sentinel lymph node. Whether such a combined lesion carries a more indolent course is also discussed.

  19. Minimally invasive breast surgery: vacuum-assisted core biopsy

    Directory of Open Access Journals (Sweden)

    A. V. Goncharov

    2017-01-01

    Full Text Available Fibrocystic breast disease is diagnosed in 20 % of women. Morphological verification of breast lumps is an important part of monitoring of these patients.Study objective. To study the role of vacuum-assisted core biopsy (VAB in differential diagnosis of fibrocystic breast disease.Materials and methods. In 2014 in Innomed plus clinic the VAB method for tumor diagnostics was introduced for the first time in the PrimorskyRegion. We studied application of VAB in 22 patients with a diagnosis of nonpalpable breast lesion.Results. Relapse rate for VAB is 4.5 %, complication rate in the form of postoperative hematomas is 22.7 %, but these complications do not increase duration of rehabilitation and are not clinically relevant.Conclusion. VAB is a minimally invasive surgical approach which allows to collect the same volume of tumor tissue as sectoral resection. The benefits of the method are better cosmetic results and shorter rehabilitation period with comparable complication rate. This allows to use VAB not only for diagnostic purposes but as a treatment for benign breast tumors.

  20. Expression of CD133, PAX2, ESA, and GPR30 in invasive ductal breast carcinomas.

    Science.gov (United States)

    Liu, Qun; Li, Ji-guang; Zheng, Xin-yu; Jin, Feng; Dong, Hui-ting

    2009-11-20

    Biomarkers in breast neoplasms provide invaluable information regarding prognosis and help determining the optimal treatment. We have examined the possible correlation between cancer stem cell (CSC)-like markers (CD133, paired box gene 2 protein (PAX2), epithelial specific antigen (ESA)), and a new membrane estrogen receptor (G-protein coupled receptor 30 (GPR30)) in invasive ductal breast carcinomas with known clinicopathological parameters, tumor recurrence, and expression of some known biomarkers. In 74 invasive ductal breast carcinomas, we investigated the protein expression of these molecular markers by immunohistochemistry, and their associations with known clinicopathological parameters, tumor recurrence, and expression of some known biomarkers. We studied the interrelationship between the expressions of these proteins. CD133, a putative CSC marker, was positively related to tumor size, tumor stage, and lymph node metastasis. PAX2 was negatively correlated with tumor recurrence. ESA, one of the breast CSC markers, was an indicator of tumor recurrence. GPR30 was associated with hormone receptors. Despite the correlation between GPR30 and the nuclear estrogen receptor, the expression was dependent. Positive staining of GPR30 in tumors displayed a significant association with high C-erbB2 expression and a tendency for tumor recurrence. A positive relationship between GPR30 and CD133 existed. Detecting the expression of CD133, PAX2, ESA, and GPR30 in invasive ductal breast carcinomas may be of help in more accurately predicting the aggressive properties of breast cancer and determining the optimal treatment.

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

    Science.gov (United States)

    Barroso-Sousa, Romualdo; Metzger-Filho, Otto

    2016-07-01

    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.

  2. Breast cancer risk prediction with heterogeneous risk profiles according to breast cancer tumor markers.

    Science.gov (United States)

    Rosner, Bernard; Glynn, Robert J; Tamimi, Rulla M; Chen, Wendy Y; Colditz, Graham A; Willett, Walter C; Hankinson, Susan E

    2013-07-15

    Relationships between some risk factors and breast cancer incidence are known to vary by tumor subtype. However, breast tumors can be classified according to a number of markers, which may be correlated, making it difficult to identify heterogeneity of risk factors with specific tumor markers when using standard competing-risk survival analysis. In this paper, we propose a constrained competing-risk survival model that allows for assessment of heterogeneity of risk factor associations according to specific tumor markers while controlling for other markers. These methods are applied to Nurses' Health Study data from 1980-2006, during which 3,398 incident invasive breast cancers occurred over 1.4 million person-years of follow-up. Results suggested that when estrogen receptor (ER) and progesterone receptor (PR) status are mutually considered, some risk factors thought to be characteristic of "estrogen-positive tumors," such as high body mass index during postmenopause and increased height, are actually significantly associated with PR-positive tumors but not ER-positive tumors, while other risk factors thought to be characteristic of "estrogen-negative tumors," such as late age at first birth, are actually significantly associated with PR-negative rather than ER-negative breast cancer. This approach provides a strategy for evaluating heterogeneity of risk factor associations by tumor marker levels while controlling for additional tumor markers.

  3. p53 mutations in classic and pleomorphic invasive lobular carcinoma of the breast.

    NARCIS (Netherlands)

    Ercan, C.; Diest, P.J. van; Ende, B. van der; Hinrichs, J.; Bult, P.; Buerger, H.; Wall, E. van der; Derksen, P.W.B.

    2012-01-01

    BACKGROUND: p53 is a tumor suppressor that is frequently mutated in human cancers. Although alterations in p53 are common in breast cancer, few studies have specifically investigated TP53 mutations in the breast cancer subtype invasive lobular carcinoma (ILC). Recently reported conditional mouse

  4. Biochemical mechanisms of tumor invasion and metastases

    DEFF Research Database (Denmark)

    Liotta, L A; Wewer, U; Rao, N C

    1988-01-01

    Cancer invasion and metastases is a complex multistep process. In order for a tumor cell to successfully traverse all the steps of this process and initiate a metastatic colony, it must express the right combination of gene products. Such gene products may include proteins which regulate cell int...

  5. Risk factors for young-onset invasive and in situ breast cancer.

    Science.gov (United States)

    O'Brien, Katie M; Sun, Jenny; Sandler, Dale P; DeRoo, Lisa A; Weinberg, Clarice R

    2015-12-01

    Young-onset breast cancers tend to be more aggressive than later-onset tumors and may have different risk factor profiles. Among young-onset cases, there may also be etiologic differences between ductal carcinomas in situ (DCIS) and invasive breast cancer, particularly if some factors promote malignant transformation. We evaluated the association between several potential risk factors and young-onset breast cancer in the Two Sister Study (2008-2010), a sister-matched case-control study involving 1,406 women diagnosed with breast cancer before age 50 (1,185 invasive, 221 DCIS) and 1,648 controls. Older age at menarche, younger age at menopause, premenopausal hysterectomy, early age at first-term pregnancy, obesity, and consumption of alcohol were associated with reduced risk of young-onset breast cancer. These patterns remained when we limited analysis to invasive breast cancers. In general, effect estimates were similar for young-onset invasive breast cancer and DCIS, although the number of DCIS cases was small. In this sister-matched case-control study of young-onset breast cancer, many of the studied risk factors were associated with young-onset invasive breast cancer. There were few discernable differences in risk factors for young-onset DCIS versus young-onset invasive breast cancer.

  6. Molecular Markers for Breast Cancer: Prediction on Tumor Behavior

    Directory of Open Access Journals (Sweden)

    Bruna Karina Banin Hirata

    2014-01-01

    Full Text Available Breast cancer is one of the most common cancers with greater than 1,300,000 cases and 450,000 deaths each year worldwide. The development of breast cancer involves a progression through intermediate stages until the invasive carcinoma and finally into metastatic disease. Given the variability in clinical progression, the identification of markers that could predict the tumor behavior is particularly important in breast cancer. The determination of tumor markers is a useful tool for clinical management in cancer patients, assisting in diagnostic, staging, evaluation of therapeutic response, detection of recurrence and metastasis, and development of new treatment modalities. In this context, this review aims to discuss the main tumor markers in breast carcinogenesis. The most well-established breast molecular markers with prognostic and/or therapeutic value like hormone receptors, HER-2 oncogene, Ki-67, and p53 proteins, and the genes for hereditary breast cancer will be presented. Furthermore, this review shows the new molecular targets in breast cancer: CXCR4, caveolin, miRNA, and FOXP3, as promising candidates for future development of effective and targeted therapies, also with lower toxicity.

  7. Macroscopic stiffness of breast tumors predicts metastasis.

    Science.gov (United States)

    Fenner, Joseph; Stacer, Amanda C; Winterroth, Frank; Johnson, Timothy D; Luker, Kathryn E; Luker, Gary D

    2014-07-01

    Mechanical properties of tumors differ substantially from normal cells and tissues. Changes in stiffness or elasticity regulate pro-metastatic behaviors of cancer cells, but effects have been documented predominantly in isolated cells or in vitro cell culture systems. To directly link relative stiffness of tumors to cancer progression, we combined a mouse model of metastatic breast cancer with ex vivo measurements of bulk moduli of freshly excised, intact tumors. We found a high, inverse correlation between bulk modulus of resected tumors and subsequent local recurrence and metastasis. More compliant tumors were associated with more frequent, larger local recurrences and more extensive metastases than mice with relatively stiff tumors. We found that collagen content of resected tumors correlated with bulk modulus values. These data establish that relative differences in tumor stiffness correspond with tumor progression and metastasis, supporting further testing and development of tumor compliance as a prognostic biomarker in breast cancer.

  8. Influence of mammographic density on the diagnostic accuracy of tumor size assessment and association with breast cancer tumor characteristics

    Energy Technology Data Exchange (ETDEWEB)

    Fasching, Peter A. [Department of Gynecology and Obstetrics, Erlangen University Hospital, Universitaetsstrasse 21-23, D-91054 Erlangen (Germany)]. E-mail: peter.fasching@gyn.med.uni-erlangen.de; Heusinger, Katharina [Department of Gynecology and Obstetrics, Erlangen University Hospital, Universitaetsstrasse 21-23, D-91054 Erlangen (Germany); Loehberg, Christian R. [Department of Gynecology and Obstetrics, Erlangen University Hospital, Universitaetsstrasse 21-23, D-91054 Erlangen (Germany); Wenkel, Evelyn [Institute of Diagnostic Radiology, Erlangen University Hospital, Erlangen (Germany); Lux, Michael P. [Department of Gynecology and Obstetrics, Erlangen University Hospital, Universitaetsstrasse 21-23, D-91054 Erlangen (Germany); Schrauder, Michael [Department of Gynecology and Obstetrics, Erlangen University Hospital, Universitaetsstrasse 21-23, D-91054 Erlangen (Germany); Koscheck, Thomas [Institute of Pathology, Friedrich Alexander University, Erlangen-Nuremberg (Germany); Bautz, Werner [Institute of Diagnostic Radiology, Erlangen University Hospital, Erlangen (Germany); Schulz-Wendtland, Ruediger [Institute of Diagnostic Radiology, Erlangen University Hospital, Erlangen (Germany); Beckmann, Matthias W. [Department of Gynecology and Obstetrics, Erlangen University Hospital, Universitaetsstrasse 21-23, D-91054 Erlangen (Germany); Bani, Mayada R. [Department of Gynecology and Obstetrics, Erlangen University Hospital, Universitaetsstrasse 21-23, D-91054 Erlangen (Germany)

    2006-12-15

    Purpose: The accuracy of breast cancer staging involves the estimation of the tumor size for the initial decision-making in the treatment. We investigated the accuracy of tumor size estimation and the association between tumor characteristics and breast density (BD). Materials and methods: A total of 434 women with a primary diagnosis of breast cancer were included in this prospective study at a specialist breast unit. Estimated tumor characteristics included tumor size, nodal status, estrogen/progesterone receptor status, Ki-67, HER2/neu, vascular invasion. Radiomorphological data included tumor size as assessed by mammography, breast ultrasonography, and clinical examination, and American College of Radiology (ACR) categories for BD. Results: BD did not have a significant impact on the assessment of tumor size using breast ultrasound (deviation from ACR categories 1-4: 0.55-0.68 cm; P = 0.331). The deviation in mammography was significantly different dependent on BD (0.42-0.9 cm; P < 0.001). The clinical examination was not affected by BD. Age and tumor size were the only parameters associated with a denser breast in the multivariate analysis. Older women were less likely to have dense breasts (odds ratio 0.157 for women aged {>=}70 years), and patients with larger tumors were less likely to have dense breasts (adjusted OR 0.36 for tumors > 2 cm). Conclusion: Breast ultrasonography is more accurate than mammography for assessing tumor size in breasts with a higher BD. The difference in tumor size assessment needs to be taken into consideration in the design of clinical trials and treatment decisions.

  9. Augmented reality for breast tumors visualization.

    Science.gov (United States)

    Ghaderi, Mohammad Ali; Heydarzadeh, Mehrdad; Nourani, Mehrdad; Gupta, Gopal; Tamil, Lakshman

    2016-08-01

    3D visualization of breast tumors are shown to be effective by previous studies. In this paper, we introduce a new augmented reality application that can help doctors and surgeons to have a more accurate visualization of breast tumors; this system uses a marker-based image-processing technique to render a 3D model of the tumors on the body. The model can be created using a combination of breast 3D mammography by experts. We have tested the system using an Android smartphone and a head-mounted device. This proof of concept can be useful for oncologists to have a more effective screening, and surgeons to plan the surgery.

  10. Ultrasonographic features of spontaneous breast tumor infarction.

    Science.gov (United States)

    Oh, Hyeon Jeong; Kim, Sung Hun; Kang, Bong Joo; Lee, A Won; Song, Byung Joo; Kim, Hyen Sook; Cha, Eun Suk

    2015-11-01

    The aim of this paper is to evaluate the ultrasonographic features of spontaneous breast tumor infarction. The pathologic information system database of the Department of Radiology was retrospectively searched. Between 2009 and 2011, nine cases in eight patients were pathologically confirmed as spontaneous breast tumor infarctions. Mammographic images and the ultrasonographic images were acquired. Two other radiologists analyzed the mammographic and ultrasonographic findings. Most common features were oval, indistinct, heterogeneously hypoechoic mass with posterior enhancement. All lesions were classified as C4 (suspicious finding) except one case. Spontaneous breast tumor infarction should be included in the differential diagnoses of hetereogeneously hypoechoic suspicious solid lesions mimicking malignancy.

  11. Identification of Claudin 1 Transcript Variants in Human Invasive Breast Cancer.

    Science.gov (United States)

    Blanchard, Anne A; Zelinski, Teresa; Xie, Jiuyong; Cooper, Steven; Penner, Carla; Leygue, Etienne; Myal, Yvonne

    2016-01-01

    The claudin 1 tight junction protein, solely responsible for the barrier function of epithelial cells, is frequently down regulated in invasive human breast cancer. The underlying mechanism is largely unknown, and no obvious mutations in the claudin 1 gene (CLDN1) have been identified to date in breast cancer. Since many genes have been shown to undergo deregulation through splicing and mis-splicing events in cancer, the current study was undertaken to investigate the occurrence of transcript variants for CLDN1 in human invasive breast cancer. RT-PCR analysis of CLDN1 transcripts was conducted on RNA isolated from 12 human invasive breast tumors. The PCR products from each tumor were resolved by agarose gel electrophoresis, cloned and sequenced. Genomic DNA was also isolated from each of the 12 tumors and amplified using PCR CLDN1 specific primers. Sanger sequencing and single nucleotide polymorphism (SNP) analyses were conducted. A number of CLDN1 transcript variants were identified in these breast tumors. All variants were shorter than the classical CLDN1 transcript. Sequence analysis of the PCR products revealed several splice variants, primarily in exon 1 of CLDN1; resulting in truncated proteins. One variant, V1, resulted in a premature stop codon and thus likely led to nonsense mediated decay. Interestingly, another transcript variant, V2, was not detected in normal breast tissue samples. Further, sequence analysis of the tumor genomic DNA revealed SNPs in 3 of the 4 coding exons, including a rare missense SNP (rs140846629) in exon 2 which represents an Ala124Thr substitution. To our knowledge this is the first report of CLDN1 transcript variants in human invasive breast cancer. These studies suggest that alternate splicing may also be a mechanism by which claudin 1 is down regulated at both the mRNA and protein levels in invasive breast cancer and may provide novel insights into how CLDN1 is reduced or silenced in human breast cancer.

  12. [Renal Cell Carcinoma with Retroperitoneal Metastases and Renal Invasion from Breast Cancer : A Case Report].

    Science.gov (United States)

    Noguchi, Go; Saito, Yoko; Mitome, Taku; Umemoto, Susumu; Kakazu, Ayano; Sugiyama, Tomoko; Ueki, Teiichiro

    2017-04-01

    A 67-year-old female was hospitalized with back pain. Computed tomography (CT) incidentally revealed a tumor in her left kidney tumor (33 mm) and bilateral breast tumors. She underwent a breast biopsy and was diagnosed with breast cancer (invasive lobular cancer, cT2N0M0). The renal tumor was suspected to be clear cell carcinoma, cT1aN0M0, based on contrast-enhanced CT. Surgery was considered necessary for both the breast cancer and renal tumor. First, laparoscopic radical nephrectomy was performed for the renal tumor. However, the lateroconal fascia adhered strongly to the perirenal fat, and so simple nephrectomy was carried out after conversion to open surgery. The perirenal fat was also excised after the nephrectomy. A histopathological examination revealed clear cell carcinoma and renal invasion by invasive lobular cancer cells. Also, scattered metastases were detected in the perirenal fat and the lateroconal fascia. So, it was considered that retroperitoneal metastases from the breast cancer had directly invaded the kidney. After the operation, the patient received hormonal therapy for her breast cancer, and she was still alive and symptom-free 5 months after the operation.

  13. Invasive lobular carcinoma of breast with synchronous colon metastasis

    Directory of Open Access Journals (Sweden)

    Zhu-Jun Loh

    2017-01-01

    Full Text Available Secondary colon malignancy is rare and has a nonspecific presentation. Breast cancer is the second most common malignancy that metastasizes to the gastrointestinal (GI tract. Here, we present the case of a 54-year-old woman diagnosed with breast cancer and synchronous colon metastasis through a positive result obtained from stool occult blood screening. Colonoscopy revealed a subepithelial tumor of the colon. Biopsy revealed metastatic cancer with positive cytokeratin and GATA-binding protein 3 staining, as well as negative caudal-type homeobox 2 staining. A palpable right breast mass with nipple retraction was found, and invasive lobular carcinoma (ILC was diagnosed. Multiple bone, left adrenal gland, para-aortic lymph node, and contralateral breast metastases were detected. Multimodality treatment involving systemic chemotherapy, hormone therapy, and modified radical mastectomy was applied. In our clinical experience, colon metastasis from breast cancer is rare and usually mimics primary colon cancer. High-alert speculation and aggressive biopsy for patients with abnormal GI bleeding are indicated for diagnosis. Patients with colon metastasis from ILC of the breast have a poor prognosis. Therefore, multimodality treatments should be applied to improve their prognosis.

  14. Intrinsic Near-Infrared Spectroscopic Markers of Breast Tumors

    OpenAIRE

    Kukreti, Shwayta; Cerussi, Albert; Tromberg, Bruce; Gratton, Enrico

    2009-01-01

    We have discovered quantitative optical biomarkers unique to cancer by developing a double-differential spectroscopic analysis method for near-infrared (NIR, 650–1000 nm) spectra acquired non-invasively from breast tumors. These biomarkers are characterized by specific NIR absorption bands. The double-differential method removes patient specific variations in molecular composition which are not related to cancer, and reveals these specific cancer biomarkers. Based on the spectral regions of a...

  15. Comparison of the clinicopathological features of invasive ductal, invasive lobular, and mixed (invasive ductal + invasive lobular) carcinoma of the breast.

    Science.gov (United States)

    Zengel, Baha; Yararbas, Ulkem; Duran, Ali; Uslu, Adam; Elıyatkın, Nukhet; Demırkıran, Mehmet Ali; Cengiz, Fevzi; Şimşek, Cenk; Postacı, Hakan; Vardar, Enver; Durusoy, Raika

    2015-07-01

    In this retrospective analysis, the clinicopathological features and pattern of metastatic spread of invasive ductal carcinoma (IDC), invasive lobular carcinoma (ILC), and mixed ductal/lobular carcinoma (MDLC), together with the type and outcome of surgical intervention, were comparatively evaluated. A total of 633 breast cancer patients with histopathological subtype IDC, ILC or MDLC were included in the study. The mean age was 52.6 ± 12.7 years. Follow-up period ranged between 0 and 33 (median 6.0) years. The groups were compared with respect to age, tumor size, nodal involvement, stage, hormonal therapy, multicentricity, multifocality, bilaterality, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2)/neu, p53, and Ki67 expression, disease-free survival (DFS) and overall survival (OS) rates, and surgical approach. The distribution of patients was as follows: IDC 508 (80.3 %), ILC 78 (12.3 %), MDLC 47 (7.4 %). Among the parameters evaluated, statistically significant differences were observed in mean tumor size (IDC 2.5 ± 1.98 cm, ILC 3.0 ± 1.8 cm, MDLC 3.2 ± 2.4 cm), advanced T stage (T3 + T4) at diagnosis (IDC 14.7 %, ILC 21.4 %, MDLC 25.6 %), N stage (N0 was dominant in IDC and ILC; N3 was dominant in MDLC), tumor-node-metastasis (TNM) stage (stage II was dominant in IDC and ILC; stage III was dominant in MDLC), HER2/neu expression (IDC 23.8 %, ILC 11.8 %, MDLC 21.4 %), and frequency of bone metastasis (IDC 14.3 %, ILC 17.9 %, MDLC 25.5 %). MDLC-type tumors have different histopathological characteristics and are often diagnosed at advanced stage. However, their survival outcomes do not vary significantly from ILC and IDC.

  16. High tumor budding stratifies breast cancer with metastatic properties.

    Science.gov (United States)

    Salhia, Bodour; Trippel, Mafalda; Pfaltz, Katrin; Cihoric, Nikola; Grogg, André; Lädrach, Claudia; Zlobec, Inti; Tapia, Coya

    2015-04-01

    Tumor budding refers to single or small cluster of tumor cells detached from the main tumor mass. In colon cancer high tumor budding is associated with positive lymph nodes and worse prognosis. Therefore, we investigated the value of tumor budding as a predictive feature of lymph node status in breast cancer (BC). Whole tissue sections from 148 surgical resection specimens (SRS) and 99 matched preoperative core biopsies (CB) with invasive BC of no special type were analyzed on one slide stained with pan-cytokeratin. In SRS, the total number of intratumoral (ITB) and peripheral tumor buds (PTB) in ten high-power fields (HPF) were counted. A bud was defined as a single tumor cell or a cluster of up to five tumor cells. High tumor budding equated to scores averaging >4 tumor buds across 10HPFs. In CB high tumor budding was defined as ≥10 buds/HPF. The results were correlated with pathological parameters. In SRS high PTB stratified BC with lymph node metastases (p ≤ 0.03) and lymphatic invasion (p ≤ 0.015). In CB high tumor budding was significantly (p = 0.0063) associated with venous invasion. Pathologists are able, based on morphology, to categorize BC into a high and low risk groups based in part on lymph node status. This risk assessment can be easily performed during routine diagnostics and it is time and cost effective. These results suggest that high PTB is associated with loco-regional metastasis, highlighting the possibility that this tumor feature may help in therapeutic decision-making.

  17. Minimally invasive approaches for diagnosis and treatment of early-stage breast cancer.

    Science.gov (United States)

    Vlastos, Georges; Verkooijen, Helena M

    2007-01-01

    Breast cancer management has been evolving toward minimally invasive approaches. Image-guided percutaneous biopsy techniques provide accurate histologic diagnosis without the need for surgical biopsy. Breast conservation therapy has become the treatment standard for early-stage breast cancer. Sentinel lymph node biopsy is a new procedure that can predict axillary lymph node status without the need of axillary lymph node dissection. The next challenge is to treat primary tumors without surgery. For this purpose, several new minimally invasive procedures, including radiofrequency ablation, interstitial laser ablation, focused ultrasound ablation, and cryotherapy, are currently under development and may offer effective tumor management and provide treatment options that are psychologically and cosmetically more acceptable to the patients than are traditional surgical therapies. In this review, we give an overview of minimally invasive approaches for the diagnostic and therapeutic management of early-stage breast cancer.

  18. Unusual aggressive breast cancer: metastatic malignant phyllodes tumor.

    Science.gov (United States)

    Singer, Adam; Tresley, Jonathan; Velazquez-Vega, Jose; Yepes, Monica

    2013-02-01

    For the year of 2012, it has been estimated that breast cancer will account for the greatest number of newly diagnosed cancers and the second highest proportion of cancer related deaths among women. Breast cancer, while often lumped together as one disease, represents a diverse group of malignancies with different imaging findings, histological appearances and behavior. While most invasive primary breast cancers are epithelial derived adenocarcinomas, rare neoplasms such as the phyllodes tumor may arise from mesenchymal tissue. Compared to the breast adenocarcinoma, the phyllodes tumor tends to affect a younger population, follows a different clinical course, is associated with different imaging and histological findings and is managed distinctively. There may be difficulty in differentiating the phyllodes tumor from a large fibroadenoma, but the mammographer plays a key role in reviewing the clinical and imaging data in order to arrive at the correct diagnosis. Early diagnosis with proper surgical management can often cure non-metastatic phyllodes tumors. However, in rare cases where metastasis occurs, prognosis tends to be poor. This report describes the presentation, imaging findings and management of a metastatic malignant phyllodes tumor.

  19. Intrinsic Near-Infrared Spectroscopic Markers of Breast Tumors

    Directory of Open Access Journals (Sweden)

    Shwayta Kukreti

    2008-01-01

    Full Text Available We have discovered quantitative optical biomarkers unique to cancer by developing a double-differential spectroscopic analysis method for near-infrared (NIR, 650–1000 nm spectra acquired non-invasively from breast tumors. These biomarkers are characterized by specific NIR absorption bands. The double-differential method removes patient specific variations in molecular composition which are not related to cancer, and reveals these specific cancer biomarkers. Based on the spectral regions of absorption, we identify these biomarkers with lipids that are present in tumors either in different abundance than in the normal breast or new lipid components that are generated by tumor metabolism. Furthermore, the O-H overtone regions (980–1000 nm show distinct variations in the tumor as compared to the normal breast. To quantify spectral variation in the absorption bands, we constructed the Specific Tumor Component (STC index. In a pilot study of 12 cancer patients we found 100% sensitivity and 100% specificity for lesion identification. The STC index, combined with other previously described tissue optical indices, further improves the diagnostic power of NIR for breast cancer detection.

  20. Pregnancy stimulates tumor angiogenesis in breast carcinoma.

    Science.gov (United States)

    Genin, Anne-Sophie; Antoine, Martine; Aractingi, Selim; Rouzier, Roman

    2014-01-01

    The mechanisms responsible for the poor prognosis of pregnancy-associated breast cancer (PABC) remain not well-understood. We studied angiogenesis and lymphangiogenesis as they are known prognostic factors in breast cancer. We conducted a case control study of breast cancer comparing women with and without PABC matched for age and histological parameters. Surgical specimen sections were immunostained with anti-CD31 for angiogenesis and anti-D2-40 for lymphangiogenesis, then analyzed using vessel density, ratio of the vascular area and the Chalkley count. Seventeen patients with PABC and 22 controls were included. Angiogenesis was significantly increased in tumor tissues, and tended to be higher in healthy breast tissues from the PABC group compared to controls. In contrast, no difference between the two groups was found concerning lymphangiogenesis both in tumor and healthy breast tissues. Pregnancy enhances angiogenesis in breast cancer. This phenomenon appears to explain the poor prognosis of PABC.

  1. Biochemical mechanisms of tumor invasion and metastases

    DEFF Research Database (Denmark)

    Liotta, L A; Wewer, U; Rao, N C

    1988-01-01

    Cancer invasion and metastases is a complex multistep process. In order for a tumor cell to successfully traverse all the steps of this process and initiate a metastatic colony, it must express the right combination of gene products. Such gene products may include proteins which regulate cell...... interaction with the basement membrane and cell motility. Tumor cells attach to the basement membrane glycoprotein laminin via the cell surface laminin receptor. The human laminin receptor was purified and molecularly cloned. The level of laminin receptor mRNA is a variety of human carcinoma cells correlated...... with the number of laminin receptors on the cell surface of these cells. Following attachment to the basement membrane, the tumor cell next secretes proteases which may degrade type IV collagen. A genetic linkage between type IV collagenase secretion and metastases was studied using our new genetic system...

  2. In-situ and invasive carcinoma within a phyllodes tumor associated with lymph node metastases

    Directory of Open Access Journals (Sweden)

    Ross Joan

    2004-12-01

    Full Text Available Abstract Background Phyllodes tumors (cystosarcoma phyllodes are uncommon lesions in the female breast. Rarely, the occurrence of carcinoma within a phyllodes tumor has been reported in the literature, but has never been associated with lymph node metastases. Case presentation A 26-year-old woman presented with a firm, mobile, non-tender mass in the left breast and palpable lymph nodes in the left axilla. The excised lesion appeared well circumscribed and lobulated, with variable fleshy and firm areas. Microscopic examination showed a circumscribed fibroepithelial lesion with a well developed leaf-like architecture, in keeping with a benign phyllodes tumor. The epithelial component showed extensive high grade ductal carcinoma in-situ (DCIS and invasive carcinoma of no special type, located entirely within the phyllodes tumor. Subsequent axillary lymph node dissection revealed metastatic carcinoma in four lymph nodes. Conclusions Although rare, phyllodes tumors may harbor DCIS and invasive carcinoma, with potential for lymph node metastasis.

  3. Cellular Potts modeling of tumor growth, tumor invasion and tumor evolution

    NARCIS (Netherlands)

    A. Szabó (Andras); R.M.H. Merks (Roeland)

    2013-01-01

    htmlabstractDespite a growing wealth of available molecular data, the growth of tumors, invasion of tumors into healthy tissue, and response of tumors to therapies are still poorly understood. Although genetic mutations are in general the first step in the development of a cancer, for the mutated

  4. The fibroblast Tiam1-osteopontin pathway modulates breast cancer invasion and metastasis.

    Science.gov (United States)

    Xu, Kun; Tian, Xuejun; Oh, Sun Y; Movassaghi, Mohammad; Naber, Stephen P; Kuperwasser, Charlotte; Buchsbaum, Rachel J

    2016-01-28

    The tumor microenvironment has complex effects in cancer pathophysiology that are not fully understood. Most cancer therapies are directed against malignant cells specifically, leaving pro-malignant signals from the microenvironment unaddressed. Defining specific mechanisms by which the tumor microenvironment contributes to breast cancer metastasis may lead to new therapeutic approaches against advanced breast cancer. We use a novel method for manipulating three-dimensional mixed cell co-cultures, along with studies in mouse xenograft models of human breast cancer and a histologic study of human breast cancer samples, to investigate how breast cancer-associated fibroblasts affect the malignant behaviors of breast cancer cells. Altering fibroblast Tiam1 expression induces changes in invasion, migration, epithelial-mesenchymal transition, and cancer stem cell characteristics in associated breast cancer cells. These changes are both dependent on fibroblast secretion of osteopontin and also long-lasting even after cancer cell dissociation from the fibroblasts, indicating a novel Tiam1-osteopontin pathway in breast cancer-associated fibroblasts. Notably, inhibition of fibroblast osteopontin with low doses of a novel small molecule prevents lung metastasis in a mouse model of human breast cancer metastasis. Moreover, fibroblast expression patterns of Tiam1 and osteopontin in human breast cancers show converse changes correlating with invasion, supporting the hypothesis that this pathway in tumor-associated fibroblasts regulates breast cancer invasiveness in human disease and is thus clinically relevant. These findings suggest a new therapeutic paradigm for preventing breast cancer metastasis. Pro-malignant signals from the tumor microenvironment with long-lasting effects on associated cancer cells may perpetuate the metastatic potential of developing cancers. Inhibition of these microenvironment signals represents a new therapeutic strategy against cancer metastasis that

  5. Myoepithelial cell-specific expression of stefin A as a suppressor of early breast cancer invasion.

    Science.gov (United States)

    Duivenvoorden, Hendrika M; Rautela, Jai; Edgington-Mitchell, Laura E; Spurling, Alex; Greening, David W; Nowell, Cameron J; Molloy, Timothy J; Robbins, Elizabeth; Brockwell, Natasha K; Lee, Cheok Soon; Chen, Maoshan; Holliday, Anne; Selinger, Cristina I; Hu, Min; Britt, Kara L; Stroud, David A; Bogyo, Matthew; Möller, Andreas; Polyak, Kornelia; Sloane, Bonnie F; O'Toole, Sandra A; Parker, Belinda S

    2017-12-01

    Mammography screening has increased the detection of early pre-invasive breast cancers, termed ductal carcinoma in situ (DCIS), increasing the urgency of identifying molecular regulators of invasion as prognostic markers to predict local relapse. Using the MMTV-PyMT breast cancer model and pharmacological protease inhibitors, we reveal that cysteine cathepsins have important roles in early-stage tumorigenesis. To characterize the cell-specific roles of cathepsins in early invasion, we developed a DCIS-like model, incorporating an immortalized myoepithelial cell line (N1ME) that restrained tumor cell invasion in 3D culture. Using this model, we identified an important myoepithelial-specific function of the cysteine cathepsin inhibitor stefin A in suppressing invasion, whereby targeted stefin A loss in N1ME cells blocked myoepithelial-induced suppression of breast cancer cell invasion. Enhanced invasion observed in 3D cultures with N1ME stefin A-low cells was reliant on cathepsin B activation, as addition of the small molecule inhibitor CA-074 rescued the DCIS-like non-invasive phenotype. Importantly, we confirmed that stefin A was indeed abundant in myoepithelial cells in breast tissue. Use of a 138-patient cohort confirmed that myoepithelial stefin A (cystatin A) is abundant in normal breast ducts and low-grade DCIS but reduced in high-grade DCIS, supporting myoepithelial stefin A as a candidate marker of lower risk of invasive relapse. We have therefore identified myoepithelial cell stefin A as a suppressor of early tumor invasion and a candidate marker to distinguish patients who are at low risk of developing invasive breast cancer, and can therefore be spared further treatment. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  6. A giant phyllodes tumor of the breast

    Directory of Open Access Journals (Sweden)

    Charlotte Schillebeeckx

    2016-10-01

    Full Text Available Phyllodes tumors of the breast are rare, accounting for less than 1% of the breast tumors. They are mostly seen in women between 45 and 49 years old. These are fast growing tumors with a large spectrum of behavior (from benign to metastatic and can resemble fibroadenomas. Correct diagnosis mostly through core needle biopsy is important to decide whether a surgical excision has to be done. Here we report a case of a 57-year-old woman with a fast growing, ulcerated tumor in the left breast. Core needle biopsy suggested a malignant phyllodes tumor with heterologous liposarcomatous differentiation. Treatment with total mastectomy and adjuvant radiotherapy followed. Primary treatment is always surgery, whether radiotherapy or chemotherapy has to follow remains uncertain. There is a high-recurrence rate, especially when the surgical margins are narrow.

  7. Stromal cells in tumor microenvironment and breast cancer.

    Science.gov (United States)

    Mao, Yan; Keller, Evan T; Garfield, David H; Shen, Kunwei; Wang, Jianhua

    2013-06-01

    Cancer is a systemic disease encompassing multiple components of both tumor cells themselves and host stromal cells. It is now clear that stromal cells in the tumor microenvironment play an important role in cancer development. Molecular events through which reactive stromal cells affect cancer cells can be defined so that biomarkers and therapeutic targets can be identified. Cancer-associated fibroblasts (CAFs) make up the bulk of cancer stroma and affect the tumor microenvironment such that they promote cancer initiation, angiogenesis, invasion, and metastasis. In breast cancer, CAFs not only promote tumor progression but also induce therapeutic resistance. Accordingly, targeting CAFs provides a novel way to control tumors with therapeutic resistance. This review summarizes the current understandings of tumor stroma in breast cancer with a particular emphasis on the role of CAFs and the therapeutic implications of CAFs. In addition, the effects of other stromal components such as endothelial cells, macrophages, and adipocytes in breast cancer are also discussed. Finally, we describe the biologic markers to categorize patients into a specific and confirmed subtype for personalized treatment.

  8. Stroma Cells in Tumor Microenvironment and Breast Cancer

    Science.gov (United States)

    Mao, Yan; Keller, Evan T.; Garfield, David H.; Shen, Kunwei; Wang, Jianhua

    2015-01-01

    Cancer is a systemic disease, encompassing multiple components of both tumor cells themselves and host stromal cells. It is now clear that stromal cells in the tumor microenvironment play an important role in cancer development. Molecular events through which reactive stromal cells affect cancer cells can be defined so that biomarkers and therapeutic targets can be identified. Cancer-associated fibroblasts (CAFs) make up the bulk of cancer stroma and affect the tumor microenvironment such that they promote cancer initiation, angiogenesis, invasion and metastasis. In breast cancer, CAFs not only promote tumor progression, but also induce therapeutic resistances. Accordingly, targeting CAFs provides a novel way to control tumors with therapeutic resistances. This review summarizes the current understanding of tumor stroma in breast cancer with a particular emphasis on the role of CAFs and the therapeutic implications of CAFs. The effects of other stromal components such as endothelial cells, macrophages and adipocytes in breast cancer are also discussed. Finally, we describe the biologic markers to sort patients into a specific and confirmed subtype for personalized treatment. PMID:23114846

  9. Biologic Profiles of Invasive Breast Cancers Detected Only With Digital Breast Tomosynthesis.

    Science.gov (United States)

    Kim, Jin You; Kang, Hyun Jung; Shin, Jong Ki; Lee, Nam Kyung; Song, You Seon; Nam, Kyung Jin; Choo, Ki Seok

    2017-12-01

    The purpose of this study was to analyze the clinicopathologic and immunohistochemical features of invasive breast cancers detected only with digital breast tomosynthesis (DBT), compared with those of cancers detected with both DBT and full-field digital mammography (FFDM). The medical records of 261 women (108 without and 153 with symptoms) with invasive breast cancers who underwent FFDM and DBT between April 2015 and June 2016 were retrospectively reviewed. To assess detectability, all DBT and FFDM images were reviewed independently by three radiologists blinded to clinicopathologic information. The reference standard was established by an unblinded consensus review of all images. Clinicopathologic and immunohistochemical features were analyzed according to the detectability status. Of the 261 cancers, 223 (85.4%) were detected with both DBT and FFDM (both-detected group). Twenty-four cancers (9.2%) not detected with FFDM (DBT-only group) were classified by DBT as a mass (58.3%), architectural distortion (33.3%), or asymmetry (8.3%). The remaining 14 cancers (5.4%) were not detected with either DBT or FFDM (both-occult group). On multivariate analysis, a dense breast parenchyma (p = 0.007), small tumor size (≤ 2 cm; p = 0.027), and luminal A-like subtype (estrogen receptor positive or progesterone receptor positive or both, human epidermal growth factor receptor 2 negative, and Ki-67 expression cancers, a dense breast parenchyma (p = 0.007) and luminal A-like subtype (p = 0.008) also maintained significance. The addition of DBT to FFDM in screening would aid in the detection of less-aggressive subtypes of invasive breast cancers in women with dense breasts.

  10. Tumor-Associated Macrophages Promote Malignant Progression of Breast Phyllodes Tumors by Inducing Myofibroblast Differentiation.

    Science.gov (United States)

    Nie, Yan; Chen, Jianing; Huang, Di; Yao, Yandan; Chen, Jiewen; Ding, Lin; Zeng, Jiayi; Su, Shicheng; Chao, Xue; Su, Fengxi; Yao, Herui; Hu, Hai; Song, Erwei

    2017-07-01

    Myofibroblast differentiation plays an important role in the malignant progression of phyllodes tumor, a fast-growing neoplasm derived from periductal stromal cells of the breast. Macrophages are frequently found in close proximity with myofibroblasts, but it is uncertain whether they are involved in the myofibroblast differentiation during phyllodes tumor progression. Here we show that increased density of tumor-associated macrophage (TAM) correlates with malignant progression of phyllodes tumor. We found that TAMs stimulated myofibroblast differentiation and promoted the proliferation and invasion of phyllodes tumor cells. Furthermore, we found that levels of the chemokine CCL18 in TAM was an independent prognostic factor of phyllodes tumor. Mechanistic investigations showed that CCL18 promoted expression of α-smooth muscle actin, a hallmark of myofibroblast, along with the proliferation and invasion of phyllodes tumor cells, and that CCL18-driven myofibroblast differentiation was mediated by an NF-κB/miR-21/PTEN/AKT signaling axis. In murine xenograft models of human phyllodes tumor, CCL18 accelerated tumor growth, induced myofibroblast differentiation, and promoted metastasis. Taken together, our findings indicated that TAM drives myofibroblast differentiation and malignant progression of phyllodes tumor through a CCL18-driven signaling cascade amenable to antibody disruption. Cancer Res; 77(13); 3605-18. ©2017 AACR . ©2017 American Association for Cancer Research.

  11. Radiation therapy-associated invasive bladder tumors

    Energy Technology Data Exchange (ETDEWEB)

    Sella, A.; Dexeus, F.H.; Chong, C.; Ro, J.Y.; Logothetis, C.J.

    1989-03-01

    Radiotherapy-associated bladder carcinoma was found in 3.7 percent of 244 cases of advanced urothelial carcinoma. Average age at diagnosis of the bladder tumor was 63.1 years, with a mean of 20.5 years between radiation treatment and diagnosis. All 9 patients presented with gross hematuria. Eight patients had transitional cell carcinoma, 7/8 (87.5%) also had vascular or lymphatic invasion, and 1 was adenocarcinoma. Mean survival was 15.4 months (range 1-40 mos.), with a 55.5 percent one-year disease-free survival after diagnosis. Four patients died of bladder tumor, 4 were alive with no evidence of disease, and 1 was alive with metastasis.

  12. Comprehensive molecular portraits of invasive lobular breast cancer

    Science.gov (United States)

    Ciriello, Giovanni; Gatza, Michael L.; Beck, Andrew H.; Wilkerson, Matthew D.; Rhie, Suhn K.; Pastore, Alessandro; Zhang, Hailei; McLellan, Michael; Yau, Christina; Kandoth, Cyriac; Bowlby, Reanne; Shen, Hui; Hayat, Sikander; Fieldhouse, Robert; Lester, Susan C.; Tse, Gary M.K.; Factor, Rachel E.; Collins, Laura C.; Allison, Kimberly H.; Chen, Yunn-Yi; Jensen, Kristen; Johnson, Nicole B.; Oesterreich, Steffi; Mills, Gordon B.; Cherniack, Andrew D.; Robertson, Gordon; Benz, Christopher; Sander, Chris; Laird, Peter W.; Hoadley, Katherine A.; King, Tari A.; Perou, Charles M.

    2015-01-01

    Summary Invasive lobular carcinoma (ILC) is the second most prevalent histologic subtype of invasive breast cancer. Here, we comprehensively profiled 817 breast tumors, including 127 ILC, 490 ductal (IDC), and 88 mixed IDC/ILC. Besides E-cadherin loss, the best known ILC genetic hallmark, we identified mutations targeting PTEN, TBX3 and FOXA1 as ILC enriched features. PTEN loss associated with increased AKT phosphorylation, which was highest in ILC among all breast cancer subtypes. Spatially clustered FOXA1 mutations correlated with increased FOXA1 expression and activity. Conversely, GATA3 mutations and high expression characterized Luminal A IDC, suggesting differential modulation of ER activity in ILC and IDC. Proliferation and immune-related signatures determined three ILC transcriptional subtypes associated with survival differences. Mixed IDC/ILC cases were molecularly classified as ILC-like and IDC-like revealing no true hybrid features. This multidimensional molecular atlas sheds new light on the genetic bases of ILC and provides potential clinical options. PMID:26451490

  13. Second harmonic generation reveals matrix alterations during breast tumor progression

    Science.gov (United States)

    Burke, Kathleen; Tang, Ping; Brown, Edward

    2013-03-01

    Alteration of the extracellular matrix in tumor stroma influences efficiency of cell locomotion away from the primary tumor into surrounding tissues and vasculature, thereby affecting metastatic potential. We study matrix changes in breast cancer through the use of second harmonic generation (SHG) of collagen in order to improve the current understanding of breast tumor stromal development. Specifically, we utilize a quantitative analysis of the ratio of forward to backward propagating SHG signal (F/B ratio) to monitor collagen throughout ductal and lobular carcinoma development. After detection of a significant decrease in the F/B ratio of invasive but not in situ ductal carcinoma compared with healthy tissue, the collagen F/B ratio is investigated to determine the evolution of fibrillar collagen changes throughout tumor progression. Results are compared with the progression of lobular carcinoma, whose F/B signature also underwent significant evolution during progression, albeit in a different manner, which offers insight into varying methods of tissue penetration and collagen manipulation between the carcinomas. This research provides insights into trends of stromal reorganization throughout breast tumor development.

  14. Bilateral malignant phyllodes tumor of the breast | Odik | Nigerian ...

    African Journals Online (AJOL)

    Phyllodes tumor is one of the breast-specific biphasic tumors, arising from the intra-lobular breast stroma. It constitutes less than 1%of all breast tumors. Bilateralmalignant phyllodes tumor is uncommon.We report a case of 32-year oldmultiparouswoman who died of multi-organ metastatic disease. The diagnosis was based ...

  15. Role of KCNMA1 gene in breast cancer invasion and metastasis to brain

    Directory of Open Access Journals (Sweden)

    Couraud Pierre-Olivier

    2009-07-01

    Full Text Available Abstract Background The prognosis for patients with breast tumor metastases to brain is extremely poor. Identification of prognostic molecular markers of the metastatic process is critical for designing therapeutic modalities for reducing the occurrence of metastasis. Although ubiquitously present in most human organs, large-conductance calcium- and voltage-activated potassium channel (BKCa channels are significantly upregulated in breast cancer cells. In this study we investigated the role of KCNMA1 gene that encodes for the pore-forming α-subunit of BKCa channels in breast cancer metastasis and invasion. Methods We performed Global exon array to study the expression of KCNMA1 in metastatic breast cancer to brain, compared its expression in primary breast cancer and breast cancers metastatic to other organs, and validated the findings by RT-PCR. Immunohistochemistry was performed to study the expression and localization of BKCa channel protein in primary and metastatic breast cancer tissues and breast cancer cell lines. We performed matrigel invasion, transendothelial migration and membrane potential assays in established lines of normal breast cells (MCF-10A, non-metastatic breast cancer (MCF-7, non-brain metastatic breast cancer cells (MDA-MB-231, and brain-specific metastatic breast cancer cells (MDA-MB-361 to study whether BKCa channel inhibition attenuates breast tumor invasion and metastasis using KCNMA1 knockdown with siRNA and biochemical inhibition with Iberiotoxin (IBTX. Results The Global exon array and RT-PCR showed higher KCNMA1 expression in metastatic breast cancer in brain compared to metastatic breast cancers in other organs. Our results clearly show that metastatic breast cancer cells exhibit increased BKCa channel activity, leading to greater invasiveness and transendothelial migration, both of which could be attenuated by blocking KCNMA1. Conclusion Determining the relative abundance of BKCa channel expression in breast

  16. Role of KCNMA1 gene in breast cancer invasion and metastasis to brain.

    Science.gov (United States)

    Khaitan, Divya; Sankpal, Umesh T; Weksler, Babette; Meister, Edward A; Romero, Ignacio A; Couraud, Pierre-Olivier; Ningaraj, Nagendra S

    2009-07-29

    The prognosis for patients with breast tumor metastases to brain is extremely poor. Identification of prognostic molecular markers of the metastatic process is critical for designing therapeutic modalities for reducing the occurrence of metastasis. Although ubiquitously present in most human organs, large-conductance calcium- and voltage-activated potassium channel (BKCa) channels are significantly upregulated in breast cancer cells. In this study we investigated the role of KCNMA1 gene that encodes for the pore-forming alpha-subunit of BKCa channels in breast cancer metastasis and invasion. We performed Global exon array to study the expression of KCNMA1 in metastatic breast cancer to brain, compared its expression in primary breast cancer and breast cancers metastatic to other organs, and validated the findings by RT-PCR. Immunohistochemistry was performed to study the expression and localization of BKCa channel protein in primary and metastatic breast cancer tissues and breast cancer cell lines. We performed matrigel invasion, transendothelial migration and membrane potential assays in established lines of normal breast cells (MCF-10A), non-metastatic breast cancer (MCF-7), non-brain metastatic breast cancer cells (MDA-MB-231), and brain-specific metastatic breast cancer cells (MDA-MB-361) to study whether BKCa channel inhibition attenuates breast tumor invasion and metastasis using KCNMA1 knockdown with siRNA and biochemical inhibition with Iberiotoxin (IBTX). The Global exon array and RT-PCR showed higher KCNMA1 expression in metastatic breast cancer in brain compared to metastatic breast cancers in other organs. Our results clearly show that metastatic breast cancer cells exhibit increased BKCa channel activity, leading to greater invasiveness and transendothelial migration, both of which could be attenuated by blocking KCNMA1. Determining the relative abundance of BKCa channel expression in breast cancer metastatic to brain and the mechanism of its action in

  17. Collagen reorganization at the tumor-stromal interface facilitates local invasion

    Directory of Open Access Journals (Sweden)

    Inman David R

    2006-12-01

    Full Text Available Abstract Background Stromal-epithelial interactions are of particular significance in breast tissue as misregulation of these interactions can promote tumorigenesis and invasion. Moreover, collagen-dense breast tissue increases the risk of breast carcinoma, although the relationship between collagen density and tumorigenesis is not well understood. As little is known about epithelial-stromal interactions in vivo, it is necessary to visualize the stroma surrounding normal epithelium and mammary tumors in intact tissues to better understand how matrix organization, density, and composition affect tumor formation and progression. Methods Epithelial-stromal interactions in normal mammary glands, mammary tumors, and tumor explants in three-dimensional culture were studied with histology, electron microscopy, and nonlinear optical imaging methodologies. Imaging of the tumor-stromal interface in live tumor tissue ex vivo was performed with multiphoton laser-scanning microscopy (MPLSM to generate multiphoton excitation (MPE of endogenous fluorophores and second harmonic generation (SHG to image stromal collagen. Results We used both laser-scanning multiphoton and second harmonic generation microscopy to determine the organization of specific collagen structures around ducts and tumors in intact, unfixed and unsectioned mammary glands. Local alterations in collagen density were clearly seen, allowing us to obtain three-dimensional information regarding the organization of the mammary stroma, such as radiating collagen fibers that could not have been obtained using classical histological techniques. Moreover, we observed and defined three tumor-associated collagen signatures (TACS that provide novel markers to locate and characterize tumors. In particular, local cell invasion was found predominantly to be oriented along certain aligned collagen fibers, suggesting that radial alignment of collagen fibers relative to tumors facilitates invasion. Consistent

  18. An unusual case of intracystic papillary carcinoma of breast with invasive component

    Directory of Open Access Journals (Sweden)

    Suryawanshi Kishor H, Nikumbh Dhiraj B, Damle Rajshri P, Dravid NV, Tayde Yogesh

    2014-07-01

    Full Text Available Papillary carcinoma of the breast is a rare malignant tumor, constituting 1-2 % of breast neoplasms mostly affecting elderly postmenopausal women. Intracystic (Encysted papillary carcinoma (IPC is a rare distinct entity with slow growth rate and overall favourable prognosis regardless of whether it is in situ alone or associated with invasive component. Treatment modalities vary from conservative surgery to radical surgery with or without adjuvant therapy depending upon the associated component (DCIS or invasive of the tumor. Herein, we report a case of 55-year-old female presented with a painless lump in the right breast. FNAC yielded haemorrhagic fluid with scanty cellularity of atypical ductal epithelial cells. Patient underwent wide local excision. The final histopathological diagnosis revealed intracystic papillary carcinoma associated with invasive ductal carcinoma, NOS type.

  19. Epstein-Barr virus infection is equally distributed across the invasive ductal and invasive lobular forms of breast cancer.

    Science.gov (United States)

    Ballard, Ashley James

    2015-12-01

    The role of Epstein-Barr virus (EBV) in the pathogenesis of breast cancer is still unclear, although a growing body of evidence supports a link. The aim of this study was to investigate if EBV infection was more prevalent in invasive ductal carcinoma or invasive lobular carcinoma. An immunohistochemical marker for EBV (Epstein-Barr virus nuclear antigen 1 (EBNA1) clone E1-2.5) was applied to a tissue micro array section. The tissue micro array contained 80 cases of invasive ductal carcinoma, and 80 cases of invasive lobular carcinoma. Each case was scored as positive or negative for nuclear expression of EBNA1 in tumor cells using standard light microscopy. EBNA1 staining was evident in the tumor cells of 63 cases (39.4% of tumor cases). By tumor type (ductal/lobular) EBV infection was noted in 34 (42.5%) cases of invasive ductal carcinoma and 29 (36.2%) cases of invasive lobular carcinoma, this difference was not found to be significant (P=0.518). This study indicates that EBV infection is equally distributed across the ductal and lobular tumor types. Copyright © 2015 Elsevier GmbH. All rights reserved.

  20. Radiographic features of invasive lobular carcinoma of the breast

    Energy Technology Data Exchange (ETDEWEB)

    Uchiyama, Nachiko; Kumazaki, Tatsuo [Nippon Medical School, Tokyo (Japan); Miyakawa, Kunihisa; Moriyama, Noriyuki

    2001-02-01

    The purpose of this study was to evaluate the radiographic features of invasive lobular carcinoma of the breast. We evaluated the radiographic features of 61 cases of histopathologically documented invasive lobular carcinoma. Mammography was performed in all cases. In seven of 61 cases, helical CT with contrast medium was also carried out. Mammographic findings were analyzed to determine true-positive and false-negative rates for the detection of neoplasm. Further, the diameter of the tumor as determined on mammography and helical CT was noted for comparison with the pathologic size. Mammographic features were divided into six types: spiculated mass (38%), indistinct mass (5%), obscured mass (23%), asymmetric opacity (16%), architectural distortion (16%), and no findings (2%). Microcalcifications were present in 12 cases (20%). The overall sensitivity rate was 59%. However, 20 (56%) of 36 cases that were diagnosed as detectable on mammography were underestimated in terms of tumor size compared with the histopathologic findings. Four cases examined by helical CT with contrast medium were compared with the histopathologic findings in terms of extent of the lesion. In three cases, helical CT was more precise than mammography, but the histopathologic findings showed lesions beyond the region evaluated by helical CT. Invasive lobular carcinoma is difficult to detect radiographically, and the extent of the lesion tends to be underestimated. (author)

  1. Immunophenotyping invasive breast cancer: paving the road for molecular imaging.

    NARCIS (Netherlands)

    Vermeulen, J.F.; Brussel, A.S. van; Groep, P. van der; Morsink, F.H.; Bult, P.; Wall, E. van der; Diest, P.J. van

    2012-01-01

    ABSTRACT: BACKGROUND: Mammographic population screening in The Netherlands has increased the number of breast cancer patients with small and non-palpable breast tumors. Nevertheless, mammography is not ultimately sensitive and specific for distinct subtypes. Molecular imaging with targeted tracers

  2. Tumor markers of breast cancer: New prospectives

    Directory of Open Access Journals (Sweden)

    Ahmed M. Kabel

    2017-04-01

    Full Text Available Tumor markers are substances produced by the tumors or by other cells of the body in response to cancer or certain benign conditions. Although most of these markers are made by the normal cells as well as by cancer cells, they are produced at much higher levels in cancerous conditions. These markers are used to evaluate the patient's response to treatment and to detect the presence of metastasis or recurrence. Breast cancer is one of the most common malignancies in females worldwide. The CA 27-29, CA 15-3, CA27.29, carcinoembryonic antigen, tissue polypeptide specific antigen, p53, cathepsin D, cyclin E, nestin and HER-2 are tumor markers that are often expressed in people with breast cancer. They play a crucial role in diagnosis, monitoring response to therapy, early detection of metastasis and determination of recurrence in patients with breast cancer.

  3. Autocrine HBEGF expression promotes breast cancer intravasation, metastasis and macrophage-independent invasion in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Z. N.; Sharma, V. P.; Beaty, B. T.; Roh-Johnson, M.; Peterson, E. A.; Van Rooijen, N.; Kenny, P. A.; Wiley, H. S.; Condeelis, J. S.; Segall, J. E.

    2014-10-13

    Increased expression of HBEGF in estrogen receptor-negative breast tumors is correlated with enhanced metastasis to distant organ sites and more rapid disease recurrence upon removal of the primary tumor. Our previous work has demonstrated a paracrine loop between breast cancer cells and macrophages in which the tumor cells are capable of stimulating macrophages through the secretion of colony-stimulating factor-1 while the tumor-associated macrophages (TAMs), in turn, aid in tumor cell invasion by secreting epidermal growth factor. To determine how the autocrine expression of epidermal growth factor receptor (EGFR) ligands by carcinoma cells would affect this paracrine loop mechanism, and in particular whether tumor cell invasion depends on spatial ligand gradients generated by TAMs, we generated cell lines with increased HBEGF expression. We found that autocrine HBEGF expression enhanced in vivo intravasation and metastasis and resulted in a novel phenomenon in which macrophages were no longer required for in vivo invasion of breast cancer cells. In vitro studies revealed that expression of HBEGF enhanced invadopodium formation, thus providing a mechanism for cell autonomous invasion. The increased invadopodium formation was directly dependent on EGFR signaling, as demonstrated by a rapid decrease in invadopodia upon inhibition of autocrine HBEGF/EGFR signaling as well as inhibition of signaling downstream of EGFR activation. HBEGF expression also resulted in enhanced invadopodium function via upregulation of matrix metalloprotease 2 (MMP2) and MMP9 expression levels. We conclude that high levels of HBEGF expression can short-circuit the tumor cell/macrophage paracrine invasion loop, resulting in enhanced tumor invasion that is independent of macrophage signaling.

  4. c-Ski activates cancer-associated fibroblasts to regulate breast cancer cell invasion.

    Science.gov (United States)

    Wang, Liyang; Hou, Yixuan; Sun, Yan; Zhao, Liuyang; Tang, Xi; Hu, Ping; Yang, Jiajia; Zeng, Zongyue; Yang, Guanglun; Cui, Xiaojiang; Liu, Manran

    2013-12-01

    Aberrant expression of c-Ski oncoprotein in some tumor cells has been shown to be associated with cancer development. However, the role of c-Ski in cancer-associated fibroblasts (CAFs) of tumor microenvironment has not been characterized. In the current study, we found that c-Ski is highly expressed in CAFs derived from breast carcinoma microenvironment and this CAF-associated c-Ski expression is associated with invasion and metastasis of human breast tumors. We showed that c-Ski overexpression in immortalized breast normal fibroblasts (NFs) induces conversion to breast CAFs by repressing p53 and thereby upregulating SDF-1 in NFs. SDF-1 treatment or p53 knockdown in NFs had similar effects on the activation of NFs as c-Ski overexpression. The c-Ski-activated CAFs show increased proliferation, migration, invasion and contraction compared with NFs. Furthermore, c-Ski-activated CAFs facilitated the migration and invasion of MDA-MB-231 breast cancer cells. Our data suggest that c-Ski is an important regulator in the activation of CAFs and may serve as a potential therapeutic target to block breast cancer progression. Copyright © 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  5. Nerve Invasion by Epithelial Cells in Benign Breast Diseases

    Directory of Open Access Journals (Sweden)

    Yu-Jan Chan

    2009-03-01

    Full Text Available Nerve invasion by glandular epithelial cells in a lesion is usually regarded as invasive carcinoma. However, some benign conditions in the pancreas, prostate, breast and other organs may show involvement of nerve bundles by benign epithelial cells. We report an 18-year-old female with nerve invasion in benign breast disease. The lesion in her right breast revealed fibrocystic changes with ductal hyperplasia and stromal sclerosis. Perineural and intraneural involvement by bland-looking small ducts lined by 2 layers of cells including an outer layer of myoepithelial cells were found, suggestive of benign nerve invasion. There was no evidence of malignant cells in any of the sections. The patient remains well after 31 months of follow-up. About 44 cases of nerve invasion in benign breast diseases have been reported in the literature. It is necessary to carefully evaluate nerve involvement in breast lesions to avoid over-diagnosis and inappropriate operation.

  6. Loss of Tumor Suppressor Merlin in Advanced Breast Cancer Is due to Post-translational Regulation*

    Science.gov (United States)

    Morrow, K. Adam; Das, Shamik; Metge, Brandon J.; Ye, Keqiang; Mulekar, Madhuri S.; Tucker, J. Allan; Samant, Rajeev S.; Shevde, Lalita A.

    2011-01-01

    Unlike malignancies of the nervous system, there have been no mutations identified in Merlin in breast cancer. As such, the role of the tumor suppressor, Merlin, has not been investigated in breast cancer. We assessed Merlin expression in breast cancer tissues by immunohistochemistry and by real-time PCR. The expression of Merlin protein (assessed immunohistochemically) was significantly decreased in breast cancer tissues (although the transcript levels were comparable) simultaneous with increased expression of the tumor-promoting protein, osteopontin (OPN). We further demonstrate that the loss of Merlin in breast cancer is brought about, in part, due to OPN-initiated Akt-mediated phosphorylation of Merlin leading to its proteasomal degradation. Restoring expression of Merlin resulted in reduced malignant attributes of breast cancer, characterized by reduced invasion, migration, motility, and impeded tumor (xenograft) growth in immunocompromised mice. The possibility of developing a model using the relationship between OPN and Merlin was tested with a logistic regression model applied to immunohistochemistry data. This identified consistent loss of immunohistochemical expression of Merlin in breast tumor tissues. Thus, we demonstrate for the first time a role for Merlin in impeding breast malignancy, identify a novel mechanism for the loss of Merlin protein in breast cancer, and have developed a discriminatory model using Merlin and OPN expression in breast tumor tissues. PMID:21965655

  7. Loss of tumor suppressor Merlin in advanced breast cancer is due to post-translational regulation.

    Science.gov (United States)

    Morrow, K Adam; Das, Shamik; Metge, Brandon J; Ye, Keqiang; Mulekar, Madhuri S; Tucker, J Allan; Samant, Rajeev S; Shevde, Lalita A

    2011-11-18

    Unlike malignancies of the nervous system, there have been no mutations identified in Merlin in breast cancer. As such, the role of the tumor suppressor, Merlin, has not been investigated in breast cancer. We assessed Merlin expression in breast cancer tissues by immunohistochemistry and by real-time PCR. The expression of Merlin protein (assessed immunohistochemically) was significantly decreased in breast cancer tissues (although the transcript levels were comparable) simultaneous with increased expression of the tumor-promoting protein, osteopontin (OPN). We further demonstrate that the loss of Merlin in breast cancer is brought about, in part, due to OPN-initiated Akt-mediated phosphorylation of Merlin leading to its proteasomal degradation. Restoring expression of Merlin resulted in reduced malignant attributes of breast cancer, characterized by reduced invasion, migration, motility, and impeded tumor (xenograft) growth in immunocompromised mice. The possibility of developing a model using the relationship between OPN and Merlin was tested with a logistic regression model applied to immunohistochemistry data. This identified consistent loss of immunohistochemical expression of Merlin in breast tumor tissues. Thus, we demonstrate for the first time a role for Merlin in impeding breast malignancy, identify a novel mechanism for the loss of Merlin protein in breast cancer, and have developed a discriminatory model using Merlin and OPN expression in breast tumor tissues.

  8. Prognostic significance of tumor budding and single cell invasion in gastric adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Che K

    2017-02-01

    Full Text Available Keying Che,1,* Yang Zhao,2,3,* Xiao Qu,1 Zhaofei Pang,1 Yang Ni,4 Tiehong Zhang,4 Jiajun Du,1,5 Hongchang Shen4 1Institute of Oncology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 2Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Collaborative Innovation Center of Cancer Medicine, Fudan University Shanghai Cancer Center, 3Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 4Department of Oncology, Shandong Provincial Hospital Affiliated to Shandong University, 5Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, People’s Republic of China *These authors contributed equally to this work Purpose: Gastric carcinoma (GC is a highly aggressive cancer and one of the leading causes of cancer-related deaths worldwide. Histopathological evaluation pertaining to invasiveness is likely to provide additional information in relation to patient outcome. In this study, we aimed to evaluate the prognostic significance of tumor budding and single cell invasion in gastric adenocarcinoma.Materials and methods: Hematoxylin and eosin-stained slides generated from 296 gastric adenocarcinoma patients with full clinical and pathological and follow-up information were systematically reviewed. The patients were grouped on the basis of tumor budding, single cell invasion, large cell invasion, mitotic count, and fibrosis. The association between histopathological parameters, different classification systems, and overall survival (OS was statistically analyzed.Results: Among the 296 cases that were analyzed, high-grade tumor budding was observed in 49.0% (145 of them. Single cell invasion and large cell invasion were observed in 62.8% (186 and 16.9% (50 of the cases, respectively. Following univariate analysis, patients with high-grade tumor budding had shorter OS than those with low-grade tumor budding (hazard ratio [HR]: 2.260, P<0

  9. Unusual Metastatic Patterns of Invasive Lobular Carcinoma of the Breast

    OpenAIRE

    Sobinsky, Justin D.; Thomas D. Willson; Podbielski, Francis J.; Connolly, Mark M.

    2013-01-01

    Invasive lobular carcinoma of the breast has similar patterns of metastatic disease when compared to invasive ductal carcinoma; however, lobular carcinoma metastasizes to unusual sites more frequently. We present a 65-year-old female with a history of invasive lobular breast carcinoma (T3N3M0) treated with modified radical mastectomy and aromatase-inhibitor therapy who underwent a surveillance PET scan, which showed possible sigmoid cancer. Colonoscopy with biopsy revealed a 3 cm sigmoid aden...

  10. Chemokine CXCL16 Expression Suppresses Migration and Invasiveness and Induces Apoptosis in Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Yeying Fang

    2014-01-01

    Full Text Available Background. Increasing evidence argues that soluble CXCL16 promotes proliferation, migration, and invasion of cancer cells in vitro. However, the role of transmembrane or cellular CXCL16 in cancer remains relatively unknown. In this study, we determine the function of cellular CXCL16 as tumor suppressor in breast cancer cells. Methods. Expression of cellular CXCL16 in breast cancer cell lines was determined at both RNA and protein levels. In vitro and in vivo studies that overexpressed or downregulated CXCL16 were conducted in breast cancer cells. Results. We report differential expression of cellular CXCL16 in breast cancer cell lines that was negatively correlated with cell invasiveness and migration. Overexpression of CXCL16 in MDA-MB-231 cells led to a decrease in cell invasion and migration and induced apoptosis of the cells; downregulation of CXCL16 in MCF-7 cells increased cell migration and invasiveness. Consistent with the in vitro data, CXCL16 overexpression inhibited tumorigenesis in vivo. Conclusions. Cellular CXCL16 suppresses invasion and metastasis of breast cancer cells in vitro and inhibits tumorigenesis in vivo. Targeting of cellular CXCL16 expression is a potential therapeutic strategy for breast cancer.

  11. Breast cancer intra-tumor heterogeneity

    Science.gov (United States)

    2014-01-01

    In recent years it has become clear that cancer cells within a single tumor can display striking morphological, genetic and behavioral variability. Burgeoning genetic, epigenetic and phenomenological data support the existence of intra-tumor genetic heterogeneity in breast cancers; however, its basis is yet to be fully defined. Two of the most widely evoked concepts to explain the origin of heterogeneity within tumors are the cancer stem cell hypothesis and the clonal evolution model. Although the cancer stem cell model appeared to provide an explanation for the variability among the neoplastic cells within a given cancer, advances in massively parallel sequencing have provided several lines of evidence to suggest that intra-tumor genetic heterogeneity likely plays a fundamental role in the phenotypic heterogeneity observed in cancers. Many challenges remain, however, in the interpretation of the next generation sequencing results obtained so far. Here we review the models that explain tumor heterogeneity, the causes of intra-tumor genetic diversity and their impact on our understanding and management of breast cancer, methods to study intra-tumor heterogeneity and the assessment of intra-tumor genetic heterogeneity in the clinic. PMID:25928070

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

    Directory of Open Access Journals (Sweden)

    Marta Hergueta-Redondo

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

  13. [Specific features of mammographic visualization of "small" breast tumors developing on the background of fibrocystic disease].

    Science.gov (United States)

    Bukharin, D G; Velichko, S A; Slonimskaia, E M; Frolova, I G; Luneva, S V; Garbukov, E Iu; Doroshenko, A V

    2011-01-01

    All complications diagnosed at early stages of breast cancer were associated with small tumors, especially with those arising in the aftermath of fibrocystic disease. Hence, our task was to study the XR-semiotics of lesions of less than 15 mm in diameter and of the same origin. 100 mammograms of breast cancer patients with benign disease of the breast were studied. The presence of moderate-to-severe fibrocystic disease significantly affected the visualization of lesions of less than 10 mm in diameter. Since the XR-semiotics of small tumors failed to reveal malignancy features, all lesions visualized by mammography required additional diagnostic procedures using ultrasound and invasive radiology.

  14. A Case of Large Phyllodes Tumor Causing “Rupture” of the Breast: A Unique Presentation

    Directory of Open Access Journals (Sweden)

    Junaid Nabi

    2013-01-01

    Full Text Available Introduction. Phyllodes tumors are rare fibroepithelial tumors which constitute less than 1% of all known breast neoplasms. The importance of recognizing these tumors lies in the need to differentiate them from fibroadenomas and other benign breast lesions to avoid inappropriate surgical management. We report a case of large phyllodes tumor which caused rupture of the breast and presented as an external fungating breast mass, a presentation which is exceedingly rare. Case Presentation. A 32-year-old female presented with a 1-year history of a mass in her right breast and eruption of the mass through the skin for the last 3 months. On physical examination, an ulcerated, irregular, and nodular mass measuring  cms was found hanging in the lower and outer quadrant of the right breast. Ultrasonography revealed an exophytic mass with heterogeneous echotexture and vascularity. Under general anesthesia, the tumor was excised. The resected specimen was  cm in size and the tumor was not invasive to the surrounding tissues. Histological examination confirmed a benign case of Phyllodes tumor. Conclusion. Clinicians should be aware of the myriad ways in which Phyllodes can present. A rapidly growing breast mass in a female should raise strong suspicion for Phyllodes. It is necessary to differentiate it from fibroadenomas to avoid inappropriate surgical management which may lead to local recurrence.

  15. Low penetrance breast cancer susceptibility loci are associated with specific breast tumor subtypes: findings from the Breast Cancer Association Consortium

    National Research Council Canada - National Science Library

    Broeks, A; Schmidt, M.K; Sherman, M.E; Couch, F.J; Hopper, J.L; Dite, G.S; Apicella, C; Smith, L.D; Hammet, F; Southey, M.C; Veer, L.J. van 't; Groot, R. de; Smit, V.T; Fasching, P.A; Beckmann, M.W; Jud, S; Ekici, A.B; Hartmann, A; Hein, A; Schulz-Wendtland, R; Burwinkel, B; Marme, F; Schneeweiss, A; Sinn, H.P; Sohn, C; Tchatchou, S; Bojesen, S.E; Nordestgaard, B.G; Flyger, H; Orsted, D.D; Kaur-Knudsen, D; Milne, R.L; Perez, J.I; Zamora, P; Roiguez, P.M; Benitez, J; Brauch, H; Justenhoven, C; Ko, Y.D; Hamann, U; Fischer, H.P; Bruning, T; Pesch, B; Chang-Claude, J; Wang-Gohrke, S; Bremer, M; Karstens, J.H; Hillemanns, P; Dork, T; Nevanlinna, H.A; Heikkinen, T; Heikkila, P; Blomqvist, C; Aittomaki, K; Aaltonen, K; Lindblom, A; Margolin, S; Mannermaa, A; Kosma, V.M; Kauppinen, J.M; Kataja, V; Auvinen, P; Eskelinen, M; Soini, Y; Chenevix-Trench, G; Spurdle, A.B; Beesley, J; Chen, X; Holland, H; Lambrechts, D; Claes, B; Vandorpe, T; Neven, P; Wildiers, H; Flesch-Janys, D; Hein, R; Loning, T; Kosel, M; Fredericksen, Z.S; Wang, X; Giles, G.G; Baglietto, L; Severi, G; McLean, C; Haiman, C.A; Henderson, B.E; Marchand, L. le; Kolonel, L.N; Alnaes, G.G; Kristensen, V; Borresen-Dale, A.L; Hunter, D.J; Hankinson, S.E; Anulis, I.L; Mulligan, A.M; O'Malley, F.P; Devilee, P; Huijts, P.E; Tollenaar, R.A.E.M; Asperen, C.J. van

    2011-01-01

    .... We investigated breast cancer risk associations of eight susceptibility loci identified in GWAS and two putative susceptibility loci in candidate genes in relation to specific breast tumor subtypes...

  16. Stable SET knockdown in breast cell carcinoma inhibits cell migration and invasion

    Energy Technology Data Exchange (ETDEWEB)

    Li, Jie [Department of Occupational Health and Occupational Medicine, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou (China); Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, Shenzhen (China); Yang, Xi-fei [Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, Shenzhen (China); Ren, Xiao-hu [Department of Occupational Health and Occupational Medicine, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou (China); Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, Shenzhen (China); Meng, Xiao-jing [Department of Occupational Health and Occupational Medicine, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou (China); Huang, Hai-yan [Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, Shenzhen (China); Zhao, Qiong-hui [Shenzhen Entry-Exit Inspection and Quarantine Bureau, Shenzhen (China); Yuan, Jian-hui; Hong, Wen-xu; Xia, Bo; Huang, Xin-feng; Zhou, Li [Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, Shenzhen (China); Liu, Jian-jun, E-mail: bio-research@hotmail.com [Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, Shenzhen (China); Zou, Fei, E-mail: zoufei616@163.com [Department of Occupational Health and Occupational Medicine, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou (China)

    2014-10-10

    Highlights: • We employed RNA interference to knockdown SET expression in breast cancer cells. • Knockdown of SET expression inhibits cell proliferation, migration and invasion. • Knockdown of SET expression increases the activity and expression of PP2A. • Knockdown of SET expression decreases the expression of MMP-9. - Abstract: Breast cancer is the most malignant tumor for women, however, the mechanisms underlying this devastating disease remain unclear. SET is an endogenous inhibitor of protein phosphatase 2A (PP2A) and involved in many physiological and pathological processes. SET could promote the occurrence of tumor through inhibiting PP2A. In this study, we explore the role of SET in the migration and invasion of breast cancer cells MDA-MB-231 and ZR-75-30. The stable suppression of SET expression through lentivirus-mediated RNA interference (RNAi) was shown to inhibit the growth, migration and invasion of breast cancer cells. Knockdown of SET increases the activity and expression of PP2Ac and decrease the expression of matrix metalloproteinase 9 (MMP-9). These data demonstrate that SET may be involved in the pathogenic processes of breast cancer, indicating that SET can serve as a potential therapeutic target for the treatment of breast cancer.

  17. Tumor microenvironment in invasive lobular carcinoma: possible therapeutic targets.

    Science.gov (United States)

    Nakagawa, Saki; Miki, Yasuhiro; Miyashita, Minoru; Hata, Shuko; Takahashi, Yayoi; Rai, Yoshiaki; Sagara, Yasuaki; Ohi, Yasuyo; Hirakawa, Hisashi; Tamaki, Kentaro; Ishida, Takanori; Watanabe, Mika; Suzuki, Takashi; Ohuchi, Noriaki; Sasano, Hironobu

    2016-01-01

    Invasive ductal and lobular carcinomas (IDC and ILC) are the two most common histological types of breast cancer, and have been considered to develop from terminal duct lobular unit but their molecular, pathological, and clinical features are markedly different between them. These differences could be due to different mechanisms of carcinogenesis and tumor microenvironment, especially cancer-associated fibroblasts (CAFs) but little has been explored in this aspect. Therefore, in this study, we evaluated the status of angiogenesis, maturation of intratumoral microvessels, and proliferation of CAFs using immunohistochemistry and PCR array analysis to explore the differences of tumor microenvironment between ILC and IDC. We studied grade- and age-matched, luminal-like ILC and IDC. We immunolocalized CD34 and αSMA for an evaluation of CAFs and CD31, Vasohibin-1, a specific marker of proliferative endothelial cells and nestin, a marker of pericytes for studying the status of proliferation and maturation of intratumoral microvessel. We also performed PCR array analysis to evaluate angiogenic factors in tumor stromal components. The number of CAFs, microvessel density, and vasohibin-1/CD31 positive ratio were all significantly higher in ILC than IDC but nestin immunoreactivity in intratumoral microvessel was significantly lower in ILC. These results did indicate that proliferation of CAFs and endothelial cells was more pronounced in ILC than IDC but newly formed microvessels were less mature than those in IDC. PCR array analysis also revealed that IGF-1 expression was higher in ILC than IDC. This is the first study to demonstrate the differences of tumor microenvironment including CAFs and proliferation and maturation of intratumoral vessels between ILC and IDC.

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

    Science.gov (United States)

    2017-06-26

    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

  19. UWB based low-cost and non-invasive practical breast cancer early detection

    Science.gov (United States)

    Vijayasarveswari, V.; Khatun, S.; Fakir, M. M.; Jusoh, M.; Ali, S.

    2017-03-01

    Breast cancer is one of the main causes of women death worldwide. Breast tumor is an early stage of cancer that locates in cells of a human breast. As there is no remedy, early detection is crucial. Towards this, Ultra-Wideband (UWB) is a prominent candidate. It is a wireless communication technology which can achieve high bandwidth with low power utilization. UWB is suitable to be used for short range communication systems including breast cancer detection since it is secure, non-invasive and human health friendly. This paper presents the low-cost and non-invasive early breast cancer detection strategy using UWB sensor (or antenna). Emphasis is given here to detect breast tumor in 2D and 3D environments. The developed system consisted of hardware and software. Hardware included UWB transceiver and a pair of home-made directional sensor/antenna. The software included feed-forward back propagation Neural Network (NN) module to detect the tumor existence, size and location along with soft interface between software and hardware. Forward scattering technique was used by placing two sensors diagonally opposite sides of a breast phantom. UWB pulses were transmitted from one side of phantom and received from other side, controlled by the software interface in PC environment. Collected received signals were then fed into the NN module for training, testing and validation. The system exhibited detection efficiency on tumor existence, location (x, y, z), and size were approximately 100%, (78.17%, 70.66%, 92.46%), 85.86% respectively. The proposed UWB based early breast cancer detection system could be more practical with low-cost, user friendly and non-harmful features. This project may help users to monitor their breast health regularly at their home.

  20. Lympho-vascular invasion in BRCA related breast cancer compared to sporadic controls

    Directory of Open Access Journals (Sweden)

    van der Wall Elsken

    2010-04-01

    Full Text Available Abstract Background Germline mutations in the BRCA1 gene predispose to the development of breast cancer, exhibiting a specific histological phenotype. Identification of possible hallmarks of these tumors is important for selecting patients for genetic screening and provides inside in carcinogenetic pathways. Since BRCA1-associated breast cancers have pushing borders that prevent them from easily reaching vessels and are often of the medullary (like type that is known to have a low rate of lympho-vascular invasion (LVI, we hypothesized that absence of LVI could characterize BRCA1 related breast cancer. Methods A population of 68 BRCA1 related invasive breast cancers was evaluated for LVI by an experienced breast pathologist blinded to mutation status, and compared to a control group matched for age, grade and tumor type. Results LVI was present in 25.0% of BRCA1 related cases, compared to 20.6% of controls (P = 0.54, OR = 1.29, CI 0.58-2.78. Conclusion LVI is frequent in BRCA1 germline mutation related breast cancers, but seems to occur as often in sporadic controls matched for age, grade and tumor type. Apparently, these hereditary cancers find their way to the blood and lymph vessels despite their well demarcation and often medullary differentiation.

  1. Osteoprotegerin mediates tumor-promoting effects of Interleukin-1beta in breast cancer cells.

    Science.gov (United States)

    Chung, Stephanie Tsang Mui; Geerts, Dirk; Roseman, Kim; Renaud, Ashleigh; Connelly, Linda

    2017-02-01

    It is widely recognized that inflammation promotes breast cancer invasion and metastasis. Given the complex nature of the breast tumor inflammatory microenvironment, much remains to be understood of the molecular mechanisms that govern these effects. We have previously shown that osteoprotegerin knockdown in breast cancer cells resulted in reduced invasion and metastasis. Here we present novel insight into the role of osteoprotegerin in inflammation-driven tumor progression in breast cancer by investigating the link between osteoprotegerin, macrophages and the potent pro-inflammatory cytokine Interleukin-1beta. We used human breast cancer cell lines to investigate the effects of Interleukin-1beta treatment on osteoprotegerin secretion as measured by ELISA. We analyzed public datasets containing human breast cancer genome-wide mRNA expression data to reveal a significant and positive correlation between osteoprotegerin mRNA expression and the mRNA expression of Interleukin-1beta and of monocyte chemoattractant protein CC-chemokine ligand 2. Osteoprotegerin, Interleukin-1beta and CC-chemokine ligand 2 mRNA levels were also examined by qPCR on cDNA from normal and cancerous human breast tissue. We determined the effect of Interleukin-1beta-producing macrophages on osteoprotegerin expression by co-culturing breast cancer cells and differentiated THP-1 macrophages. Immunohistochemistry was performed on human breast tumor tissue microarrays to assess macrophage infiltration and osteoprotegerin expression. To demonstrate that osteoprotegerin mediated functional effects of Interleukin-1beta we performed cell invasion studies with control and OPG siRNA knockdown on Interleukin-1beta-treated breast cancer cells. We report that Interleukin-1beta induces osteoprotegerin secretion, independent of breast cancer subtype and basal osteoprotegerin levels. Co-culture of breast cancer cells with Interleukin-1beta-secreting macrophages resulted in a similar increase in osteoprotegerin

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

    Science.gov (United States)

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

    2016-05-05

    Breast cancer in men is uncommon, accounting for 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. 2016 BMJ Publishing Group Ltd.

  3. Multifocal and Multicentric Breast Carcinoma: A Significantly More Aggressive Tumor than Unifocal Breast Cancer.

    Science.gov (United States)

    Lang, Zhiqiang; Wu, Yanqiu; Li, Cuiyan; Li, Xinna; Wang, Xuan; Qu, Guimei

    2017-08-01

    There are still many questions that surround multifocal or multicentric breast carcinoma (MMBC). The aim of this study was to analyze the clinicopathological characteristics of MMBC and provide feasible suggestions for therapy. A total of 156 cases of MMBC in 3,597 invasive ductal breast carcinomas were collected and reviewed. Some factors related with prognosis such as tumor size, lymph node metastasis and others were assessed in each tumor focus, and mismatches among foci were recorded. The majority of MMBC had aggregate dimensions over 2 cm (85.90%). The rate of axillary lymph node metastasis was 56.41% (88/156) compared to unifocal tumors of 33.01% (1,136/3,441). Most cases had higher Ki-67 proliferative indices (91/156). Mismatches in ER status were present in 6 cases, PR in 4 cases, proliferative index (Ki-67) in 9 cases and HER2-positive status in 2 cases. The larger aggregate dimension of tumor, the higher metastatic rate of axillary lymph node and the high Ki-67 proliferative index seen in most cases, suggest that MMBC is biologically more aggressive than unifocal breast cancer. In addition, every focus should be tested owing to the existence of different expressions of immunostaining between foci. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

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

    Energy Technology Data Exchange (ETDEWEB)

    Sedlmayer, F. [Paracelsus Medical Univ. Hospital, Salzburg (Austria). Dept. of Radiotherapy and Radiation Oncology; Sautter-Bihl, M.L. [Staedtisches Klinium Karlsruhe (Germany). Klinik fuer Radioonkologie und Strahlentherapie; Budach, W. [University Hospital Duesseldorf (Germany)] [and others

    2013-10-15

    Background and purpose: The aim of the present paper is to update the practical guidelines for postoperative adjuvant radiotherapy of breast cancer published in 2007 by the breast cancer expert panel of the German Society for Radiooncology (Deutsche Gesellschaft fuer Radioonkologie, DEGRO). The present recommendations are based on a revision of the German interdisciplinary S-3 guidelines published in July 2012. Methods: A comprehensive survey of the literature concerning radiotherapy following breast conserving therapy (BCT) was performed using the search terms 'breast cancer', 'radiotherapy', and 'breast conserving therapy'. Data from lately published meta-analyses, recent randomized trials, and guidelines of international breast cancer societies, yielding new aspects compared to 2007, provided the basis for defining recommendations according to the criteria of evidence-based medicine. In addition to the more general statements of the DKG (Deutsche Krebsgesellschaft), this paper addresses indications, target definition, dosage, and technique of radiotherapy of the breast after conservative surgery for invasive breast cancer. Results: Among numerous reports on the effect of radiotherapy during BCT published since the last recommendations, the recent EBCTCG report builds the largest meta-analysis so far available. In a 15 year follow-up on 10,801 patients, whole breast irradiation (WBI) halves the average annual rate of disease recurrence (RR 0.52, 0.48-0.56) and reduces the annual breast cancer death rate by about one sixth (RR 0.82, 0.75-0.90), with a similar proportional, but different absolute benefit in prognostic subgroups (EBCTCG 2011). Furthermore, there is growing evidence that risk-adapted dose augmentation strategies to the tumor bed as well as the implementation of high precision RT techniques (e.g., intraoperative radiotherapy) contribute substantially to a further reduction of local relapse rates. A main focus of ongoing

  5. Human breast adipose tissue: characterization of factors that change during tumor progression in human breast cancer.

    Science.gov (United States)

    Fletcher, Sabrina Johanna; Sacca, Paula Alejandra; Pistone-Creydt, Mercedes; Coló, Federico Andrés; Serra, María Florencia; Santino, Flavia Eliana; Sasso, Corina Verónica; Lopez-Fontana, Constanza Matilde; Carón, Rubén Walter; Calvo, Juan Carlos; Pistone-Creydt, Virginia

    2017-02-07

    Adipose microenvironment is involved in signaling pathways that influence breast cancer. We aim to characterize factors that are modified: 1) in tumor and non tumor human breast epithelial cell lines when incubated with conditioned media (CMs) from human breast cancer adipose tissue explants (hATT) or normal breast adipose tissue explants (hATN); 2) in hATN-CMs vs hATT-CMs; 3) in the tumor associated adipocytes vs. non tumor associated adipocytes. We used hATN or hATT- CMs on tumor and non-tumor breast cancer cell lines. We evaluated changes in versican, CD44, ADAMTS1 and Adipo R1 expression on cell lines or in the different CMs. In addition we evaluated changes in the morphology and expression of these factors in slices of the different adipose tissues. The statistical significance between different experimental conditions was evaluated by one-way ANOVA. Tukey's post-hoc tests were performed within each individual treatment. hATT-CMs increase versican, CD44, ADAMTS1 and Adipo R1 expression in breast cancer epithelial cells. Furthermore, hATT-CMs present higher levels of versican expression compared to hATN-CMs. In addition, we observed a loss of effect in cellular migration when we pre-incubated hATT-CMs with chondroitinase ABC, which cleaves GAGs chains bound to the versican core protein, thus losing the ability to bind to CD44. Adipocytes associated with the invasive front are reduced in size compared to adipocytes that are farther away. Also, hATT adipocytes express significantly higher amounts of versican, CD44 and Adipo R1, and significantly lower amounts of adiponectin and perilipin, unlike hATN adipocytes. We conclude that hATT secrete a different set of proteins compared to hATN. Furthermore, versican, a proteoglycan that is overexpressed in hATT-CMs compared to hATN-CMs, might be involved in the tumorogenic behavior observed in both cell lines employed. In addition, we may conclude that adipocytes from the tumor microenvironment show a less differentiated

  6. Ultrasound imaging of breast tumor perfusion and neovascular morphology.

    Science.gov (United States)

    Hoyt, Kenneth; Umphrey, Heidi; Lockhart, Mark; Robbin, Michelle; Forero-Torres, Andres

    2015-09-01

    A novel image processing strategy is detailed for simultaneous measurement of tumor perfusion and neovascular morphology parameters from a sequence of dynamic contrast-enhanced ultrasound (DCE-US) images. After normalization and tumor segmentation, a global time-intensity curve describing contrast agent flow was analyzed to derive surrogate measures of tumor perfusion (i.e., peak intensity, time-to-peak intensity, area under the curve, wash-in rate, wash-out rate). A maximum intensity image was generated from these same segmented image sequences, and each vascular component was skeletonized via a thinning algorithm. This skeletonized data set and collection of vessel segments were then investigated to extract parameters related to the neovascular network and physical architecture (i.e., vessel-to-tissue ratio, number of bifurcations, vessel count, average vessel length and tortuosity). An efficient computation of local perfusion parameters was also introduced and operated by averaging time-intensity curve data over each individual neovascular segment. Each skeletonized neovascular segment was then color-coded by these local measures to produce a parametric map detailing spatial properties of tumor perfusion. Longitudinal DCE-US image data sets were collected in six patients diagnosed with invasive breast cancer using a Philips iU22 ultrasound system equipped with a L9-3 transducer and Definity contrast agent. Patients were imaged using US before and after contrast agent dosing at baseline and again at weeks 6, 12, 18 and 24 after treatment started. Preliminary clinical results suggested that breast tumor response to neoadjuvant chemotherapy may be associated with temporal and spatial changes in DCE-US-derived parametric measures of tumor perfusion. Moreover, changes in neovascular morphology parametric measures may also help identify any breast tumor response (or lack thereof) to systemic treatment. Breast cancer management from early detection to therapeutic

  7. Quantitative histopathological variables in in situ and invasive ductal and lobular carcinomas of the breast

    DEFF Research Database (Denmark)

    Ladekarl, M; Sørensen, Flemming Brandt

    1993-01-01

    This study was carried out to compare quantitative histopathological estimates obtained in normal breast epithelium (N = 15), lobular carcinoma in situ (N = 29), ductal carcinoma in situ (N = 24), invasive lobular carcinoma (N = 39), and invasive ductal carcinoma (N = 71) of the female breast......, and invasive carcinomas. Overlaps were, however, evident among the groups. There were no significant differences between means of the quantitative variables obtained in carcinoma in situ of the ductal and the lobular type with or without accompanying invasive carcinoma (2p > or = 0.22). A close correlation......, and the nuclear volume fraction, Vv(nuc/tis). The vv(nuc), aH(nuc), and MI were, on average, larger in ductal than in lobular carcinomas (2p carcinomas (2p = 3.10(-4). Comparing estimates obtained in tumors of pure ductal carcinoma in situ (N = 11) with those...

  8. Tumor Budding in Breast Carcinoma: Relation to E-Cadherin, MMP-9 Expression, and Metastasis Risk

    Directory of Open Access Journals (Sweden)

    Ni Putu Sriwidyani

    2016-10-01

    Full Text Available Background: Tumor budding is a histopathologic entity refers to small cluster of cancer cells at the invasive edge of tumor. It was assumed that tumor budding is linked to epithelial-mesenchymal transition, an early event in metastasis. Objective: This study aimed to find out the correlation of tumor budding with E-cadherin and MMP-9 expression and risk of metastasis in breast carcinoma. Method: We investigated 35 cases breast carcinoma with metastasis and 35 cases without metastasis. The number of tumor budding was counted in cytokeratin-stained slides with 400x magnification (0.57 mm2. Result: Cut-off point by ROC analysis was 11 and the patient was categorized into low grade (0-10 buds and high grade (11 or more buds tumor budding. Inter-observer agreement was good with K value 0.914. Low level of E-cadherin was not significantly correlated with high grade tumor budding (p=0.660, meanwhile high level of MMP-9 was significantly correlated with high grade tumor budding (p=0.001. High grade tumor budding was a significant, independent risk factor of metastasis in breast carcinoma (OR=38.2, 95% CI 7.5-193.7, p<0.001. Conclusion: In conclusion, tumor budding grade is related to level of MMP-9 but has no correlation E-cadherin expression. High grade tumor budding is an independent risk factor of metastasis in breast carcinoma.

  9. Targeting of RAGE-ligand signaling impairs breast cancer cell invasion and metastasis.

    Science.gov (United States)

    Kwak, T; Drews-Elger, K; Ergonul, A; Miller, P C; Braley, A; Hwang, G H; Zhao, D; Besser, A; Yamamoto, Y; Yamamoto, H; El-Ashry, D; Slingerland, J M; Lippman, M E; Hudson, B I

    2017-03-01

    The receptor for advanced glycation end products (RAGE) is highly expressed in various cancers and is correlated with poorer outcome in breast and other cancers. Here we tested the role of targeting RAGE by multiple approaches in the tumor and tumor microenvironment, to inhibit the metastatic process. We first tested how RAGE impacts tumor cell-intrinsic mechanisms using either RAGE overexpression or knockdown with short hairpin RNAs (shRNAs). RAGE ectopic overexpression in breast cancer cells increased MEK-EMT (MEK-epithelial-to-mesenchymal transition) signaling, transwell invasion and soft agar colony formation, and in vivo promoted lung metastasis independent of tumor growth. RAGE knockdown with multiple independent shRNAs in breast cancer cells led to decreased transwell invasion and soft agar colony formation, without affecting proliferation. In vivo, targeting RAGE shRNA knockdown in human and mouse breast cancer cells, decreased orthotopic tumor growth, reduced tumor angiogenesis and recruitment of inflammatory cells, and markedly decreased metastasis to the lung and liver in multiple xenograft and syngeneic mouse models. To test the non-tumor cell microenvironment role of RAGE, we performed syngeneic studies with orthotopically injected breast cancer cells in wild-type and RAGE-knockout C57BL6 mice. RAGE-knockout mice displayed striking impairment of tumor cell growth compared with wild-type mice, along with decreased mitogen-activated protein kinase signaling, tumor angiogenesis and inflammatory cell recruitment. To test the combined inhibition of RAGE in both tumor cell-intrinsic and non-tumor cells of the microenvironment, we performed in vivo treatment of xenografted tumors with FPS-ZM1 (1 mg/kg, two times per week). Compared with vehicle, FPS-ZM1 inhibited primary tumor growth, inhibited tumor angiogenesis and inflammatory cell recruitment and, most importantly, prevented metastasis to the lung and liver. These data demonstrate that RAGE drives tumor

  10. Tumor markers of breast cancer: New prospectives

    OpenAIRE

    Ahmed M. Kabel

    2017-01-01

    Tumor markers are substances produced by the tumors or by other cells of the body in response to cancer or certain benign conditions. Although most of these markers are made by the normal cells as well as by cancer cells, they are produced at much higher levels in cancerous conditions. These markers are used to evaluate the patient's response to treatment and to detect the presence of metastasis or recurrence. Breast cancer is one of the most common malignancies in females worldwide. The CA 2...

  11. Recurrent malignant phyllodes tumor of the breast: A case report.

    Science.gov (United States)

    Wang, Qinqin; Su, Jing; Lei, Yutao

    2017-12-01

    Phyllodes tumor is a rare fibro epithelial neoplasm of the breast. They resemble fibroadenomas clinically and can be mistakenly ignored sometimes. We report the case of a young woman with her first presentation to hospital due to a hypoglycemia and she underwent 2 excised fibroadenomas in the same breast before diagnosed of malignant phyllodes tumor. She was complaining about 2 masses presented in her right breast 4 months after mastectomy. Recurrent phyllodes tumor of the breast. We conducted an immediate autologous myocutaneous flap transplantation after a wide-excision. Postoperative radiotherapy was recommended. She was in good general condition without tumor relapses during 8 months of follow-up. Recurrent fibroadenomas in the same breast, especially those of large size with rapid growth rate, suggesting a high transformation possibility from fibroadenoma to phyllodes tumor. We recommend an extended tumor resection and immediate or delayed reconstruction of the breast for the recurrent phyllodes tumor with separately multiple relapses.

  12. Invasive lobular carcinoma arising in accessory breast tissue

    OpenAIRE

    Devine, Catriona; Courtney, Carol-Ann; Deb, Rahul; Agrawal, Amit

    2013-01-01

    Background: Lobular carcinoma in accessory breast tissue is a rare occurrence. We present such a case in a 61-year-old woman. \\ud \\ud Case presentation: A skin nodule in the axillary skin on excision biopsy revealed invasive lobular carcinoma.\\ud \\ud Conclusions: Carcinoma in accessory breast tissue is uncommon especially invasive lobular type. A high index of suspicion may avoid late diagnosis.

  13. Photonic Breast Tomography and Tumor Aggressiveness Assessment

    Science.gov (United States)

    2009-07-01

    Caspase-3. • Drug (PD901) treatment and cell growth curve m easurement for OVCAR5, T24 , and UMUC3 cell lines. • Flow cytometry technique for cell ...spectroscopic approaches for breast tumor detection. The CCNY researchers received training on (i) small animal handling; (ii) Cell culture, bioluminescence...aging techniques, cell culture, bioluminescence assay, Western Blotting, and other key techniques used in cancer research. Rotation I Laboratory

  14. 14-3-3τ promotes breast cancer invasion and metastasis by inhibiting RhoGDIα.

    Science.gov (United States)

    Xiao, Yang; Lin, Vivian Y; Ke, Shi; Lin, Gregory E; Lin, Fang-Tsyr; Lin, Weei-Chin

    2014-07-01

    14-3-3τ is frequently overexpressed in breast cancer; however, whether it contributes to breast cancer progression remains undetermined. Here, we identify a critical role for 14-3-3τ in promoting breast cancer metastasis, in part through binding to and inhibition of RhoGDIα, a negative regulator of Rho GTPases and a metastasis suppressor. 14-3-3τ binds Ser174-phosphorylated RhoGDIα and blocks its association with Rho GTPases, thereby promoting epidermal growth factor (EGF)-induced RhoA, Rac1, and Cdc42 activation. When 14-3-3τ is overexpressed in MCF7 breast cancer cells that express 14-3-3τ at low levels, it increases motility, reduces adhesion, and promotes metastasis in mammary fat pad xenografts. On the other hand, depletion of 14-3-3τ in MCF7 cells and in an invasive cell line, MDA-MB231, inhibits Rho GTPase activation and blocks breast cancer migration and invasion. Moreover, 14-3-3τ overexpression in human breast tumors is associated with the activation of ROCK (a Rho GTPase effector), high metastatic rate, and shorter survival, underscoring a clinically significant role for 14-3-3τ in breast cancer progression. Our work indicates that 14-3-3τ is a novel therapeutic target to prevent breast cancer metastasis.

  15. Invasive lobular carcinoma of the male breast - a systematic review with an illustrative case study.

    Science.gov (United States)

    Senger, Jenna-Lynn; Adams, Scott J; Kanthan, Rani

    2017-01-01

    Male breast cancer is rare, comprising only 1% of all mammary cancers; invasive ductal carcinoma is by far the commonest subtype in both men and women. Though lobular breast cancer is the second most common subtype seen in women, such cancers are extremely uncommon in men, and this is likely related to the lack of lobular development in the male breast. Thus, due to the rarity of this subtype among breast cancers, compounded by the overall rarity of breast cancer in men, current understanding of the pathogenesis of this disease and its management is largely derived from case series and extrapolation of information from the larger cohort of female patients. This paper provides a systematic review on invasive lobular carcinoma of the male breast in the context of an illustrative case study. A comprehensive analysis of the National Cancer Institute's Surveillance, Epidemiology, and End Results Data 1973-2013 leading to an exploration of the pathogenesis, epidemiology, clinical presentation, diagnosis, tumor characteristics, and management of lobular breast carcinoma in men is also discussed. Lobular subtype of breast cancer remains an enigmatic elusive disease that needs additional research to unravel its overall pathogenesis and molecular profile to provide insight for improved therapeutic management options.

  16. Invasive lobular carcinoma of the male breast – a systematic review with an illustrative case study

    Science.gov (United States)

    Senger, Jenna-Lynn; Adams, Scott J; Kanthan, Rani

    2017-01-01

    Male breast cancer is rare, comprising only 1% of all mammary cancers; invasive ductal carcinoma is by far the commonest subtype in both men and women. Though lobular breast cancer is the second most common subtype seen in women, such cancers are extremely uncommon in men, and this is likely related to the lack of lobular development in the male breast. Thus, due to the rarity of this subtype among breast cancers, compounded by the overall rarity of breast cancer in men, current understanding of the pathogenesis of this disease and its management is largely derived from case series and extrapolation of information from the larger cohort of female patients. This paper provides a systematic review on invasive lobular carcinoma of the male breast in the context of an illustrative case study. A comprehensive analysis of the National Cancer Institute’s Surveillance, Epidemiology, and End Results Data 1973–2013 leading to an exploration of the pathogenesis, epidemiology, clinical presentation, diagnosis, tumor characteristics, and management of lobular breast carcinoma in men is also discussed. Lobular subtype of breast cancer remains an enigmatic elusive disease that needs additional research to unravel its overall pathogenesis and molecular profile to provide insight for improved therapeutic management options. PMID:28553141

  17. Diagnosis and minimally invasive treatment of early stage breast carcinoma

    NARCIS (Netherlands)

    van Esser, S.

    1979-01-01

    In this thesis the diagnostic work up and minimally invasive surgical treatment of early stage breast carcinoma is studied. Although the surgical treatment of breast carcinoma has improved significantly over the past decades, there is still room for improvement. On the one hand the focus is on early

  18. Clinical, histomorphological, and therapeutic prognostic factors in patients with triple-negative invasive breast cancer

    Directory of Open Access Journals (Sweden)

    Camila M. Lopes

    2015-12-01

    Full Text Available ABSTRACT Introduction: Breast cancer is the most common visceral malignancy in women, the leading cause of cancer death among women worldwide. The triple negative subgroup has poor prognosis and aggressive biological behavior. Objectives: To outline the clinical and histopathological aspects, the treatment profile, and to suggest which factors may predict poor prognosis in patients with triple-negative invasive breast cancer in the Campos Gerais region of Paraná. Methods: A retrospective observational cohort study, longitudinal, comparative, performed in a clinic of anatomic pathology in the Instituto Sul Paranaense de Oncologia, in Ponta Grossa, Paraná. The inclusion criteria were female patients with pathology report of invasive breast carcinoma, whose immunohistochemistry showed negative for hormone receptors and human epidermal growth factor receptor (HER2, diagnosed in the period between January 1, 2002 and December 31, 2012. The patients were divided into two groups, living women and patients who have died. Results: The recurrence rate, chemotherapy type, angiolymphatic invasion, tumor size, lymph node invasion, and type of surgery performed were significant variables in the univariate analysis between the groups. After Cox regression for multivariate analysis, only the angiolymphatic invasion (p = 0.012, relative risk [RR] 5.0518, confidence interval [CI] 95% 1.4261-17.8952, and tumor size (p = 0.0385, RR 1.2605, CI 95% 1.0123-1.5695 remained significant. Conclusion: The angiolymphatic invasion and tumor size proved to be risk factors for death, from all causes, in patients with triple-negative breast cancer. Differences between groups can indicate different molecular subtypes within the triple-negative phenotype.

  19. GPR54 (KISS1R) transactivates EGFR to promote breast cancer cell invasiveness.

    Science.gov (United States)

    Zajac, Mateusz; Law, Jeffrey; Cvetkovic, Dragana Donna; Pampillo, Macarena; McColl, Lindsay; Pape, Cynthia; Di Guglielmo, Gianni M; Postovit, Lynne M; Babwah, Andy V; Bhattacharya, Moshmi

    2011-01-01

    Kisspeptins (Kp), peptide products of the Kisspeptin-1 (KISS1) gene are endogenous ligands for a G protein-coupled receptor 54 (GPR54). Previous findings have shown that KISS1 acts as a metastasis suppressor in numerous cancers in humans. However, recent studies have demonstrated that an increase in KISS1 and GPR54 expression in human breast tumors correlates with higher tumor grade and metastatic potential. At present, whether or not Kp signaling promotes breast cancer cell invasiveness, required for metastasis and the underlying mechanisms, is unknown. We have found that kisspeptin-10 (Kp-10), the most potent Kp, stimulates the invasion of human breast cancer MDA-MB-231 and Hs578T cells using Matrigel-coated Transwell chamber assays and induces the formation of invasive stellate structures in three-dimensional invasion assays. Furthermore, Kp-10 stimulated an increase in matrix metalloprotease (MMP)-9 activity. We also found that Kp-10 induced the transactivation of epidermal growth factor receptor (EGFR). Knockdown of the GPCR scaffolding protein, β-arrestin 2, inhibited Kp-10-induced EGFR transactivation as well as Kp-10 induced invasion of breast cancer cells via modulation of MMP-9 secretion and activity. Finally, we found that the two receptors associate with each other under basal conditions, and FRET analysis revealed that GPR54 interacts directly with EGFR. The stability of the receptor complex formation was increased upon treatment of cells by Kp-10. Taken together, our findings suggest a novel mechanism by which Kp signaling via GPR54 stimulates breast cancer cell invasiveness.

  20. GPR54 (KISS1R transactivates EGFR to promote breast cancer cell invasiveness.

    Directory of Open Access Journals (Sweden)

    Mateusz Zajac

    Full Text Available Kisspeptins (Kp, peptide products of the Kisspeptin-1 (KISS1 gene are endogenous ligands for a G protein-coupled receptor 54 (GPR54. Previous findings have shown that KISS1 acts as a metastasis suppressor in numerous cancers in humans. However, recent studies have demonstrated that an increase in KISS1 and GPR54 expression in human breast tumors correlates with higher tumor grade and metastatic potential. At present, whether or not Kp signaling promotes breast cancer cell invasiveness, required for metastasis and the underlying mechanisms, is unknown. We have found that kisspeptin-10 (Kp-10, the most potent Kp, stimulates the invasion of human breast cancer MDA-MB-231 and Hs578T cells using Matrigel-coated Transwell chamber assays and induces the formation of invasive stellate structures in three-dimensional invasion assays. Furthermore, Kp-10 stimulated an increase in matrix metalloprotease (MMP-9 activity. We also found that Kp-10 induced the transactivation of epidermal growth factor receptor (EGFR. Knockdown of the GPCR scaffolding protein, β-arrestin 2, inhibited Kp-10-induced EGFR transactivation as well as Kp-10 induced invasion of breast cancer cells via modulation of MMP-9 secretion and activity. Finally, we found that the two receptors associate with each other under basal conditions, and FRET analysis revealed that GPR54 interacts directly with EGFR. The stability of the receptor complex formation was increased upon treatment of cells by Kp-10. Taken together, our findings suggest a novel mechanism by which Kp signaling via GPR54 stimulates breast cancer cell invasiveness.

  1. Macrophage Polarization: Anti-Cancer Strategies to Target Tumor-Associated Macrophage in Breast Cancer.

    Science.gov (United States)

    Tariq, Muhammad; Zhang, Jieqiong; Liang, Guikai; Ding, Ling; He, Qiaojun; Yang, Bo

    2017-09-01

    Tumor-associated macrophages (TAMs) are the most abundant inflammatory cells and orchestrate different stages of breast cancer development. TAMs participate in the tumor angiogenesis, matrix remodeling, invasion, immunosuppression, metastasis, and chemoresistance in breast cancer. Several clinical studies indicate the association between the high influx of TAMs in tumor with poor prognosis in hepatocellular, ovarian, cervical, and breast cancer. Previously developed hypotheses have proposed that TAMs participate in antitumor responses of the body, while recently many clinical and experimental studies have revealed that TAMs in tumor microenvironment predominantly resemble with M2-like polarized macrophages and produce a high amount of anti-inflammatory factors which are directly responsible for the development of tumor. Various studies have shown that TAMs in tumor either enhance or antagonize the anti-tumor efficacy of cytotoxic agents, antibodies-targeting cancer cells, and therapeutic agents depending on the nature of treatment. Thereby, multiple roles of TAMs suggests that it is very important to develop novel therapeutic strategies to target TAMs in breast tumor. In this review, we have discussed the functional role of TAMs in breast cancer and summarized available recent advances potential therapeutic strategies that effectively target to TAMs cells. J. Cell. Biochem. 118: 2484-2501, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  2. Malignant phyllodes tumor of the breast: a case study.

    Science.gov (United States)

    Keim-Malpass, Jessica; Mills, Anne M; Showalter, Shayna L

    2014-10-01

    Malignant phyllodes tumors of the breast are rare, fast-growing tumors that can be difficult to diagnose. A case study is featured about a young adult patient who lacked insurance and received a delayed diagnosis of malignant phyllodes tumor of the breast. This article includes pertinent clinical and age-specific considerations for comprehensive management.

  3. Silencing of miRNA-218 promotes migration and invasion of breast cancer via Slit2-Robo1 pathway.

    Science.gov (United States)

    Yang, Longqiu; Li, Qing; Wang, Qingxiu; Jiang, Zhen; Zhang, Lei

    2012-10-01

    MiRNAs play an important role in regulating tumor migration and invasion, and abnormal expression of miRNAs occurs in various kinds of human cancers. In this essay, it is reported that the level of miRNA-218 decreases in metastatic breast cancer cells, moreover, miRNA-218 suppresses breast cancer cells migration and invasion through binding Robo1 (one of Slit receptors) to its 3'UTR. MiRNA-218 restoration suppresses Robo1 expression and inhibits breast cancer cells invasion and migration. What the results describe is that the function of Robo1 regulated by miRNA-218 may provide a new strategy for inhibiting migration and invasion of breast cancer cells. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  4. Identification of genes and pathways related to lymphovascular invasion in breast cancer patients: A bioinformatics analysis of gene expression profiles.

    Science.gov (United States)

    Klahan, Sukhontip; Wong, Henry Sung-Ching; Tu, Shih-Hsin; Chou, Wan-Hsuan; Zhang, Yan-Feng; Ho, Thien-Fiew; Liu, Chih-Yi; Yih, Shih-Ying; Lu, Hsing Fang; Chen, Sean Chun-Chang; Huang, Chi-Cheng; Chang, Wei-Chiao

    2017-06-01

    Surgery is the most effective treatment for breast cancer patients. However, some patients developed recurrence and distant metastasis after surgery. Adjuvant therapy is considered for high-risk patients depending on several prognostic markers, and lymphovascular invasion has become one of such prognostic markers that help physicians to identify the risk for distant metastasis and recurrence. However, the mechanism of lymphovascular invasion in breast cancer remains unknown. This study aims to unveil the genes and pathways that may involve in lymphovascular invasion in breast cancer. In total, 108 breast cancer samples were collected during surgery and microarray analysis was performed. Significance analysis of the microarrays and limma package for R were used to examine differentially expressed genes between lymphovascular invasion-positive and lymphovascular invasion-negative cases. Network and pathway analyses were mapped using the Ingenuity Pathway Analysis and the Database for Annotation, Visualization and Integrated Discovery. In total, 86 differentially expressed genes, including 37 downregulated genes and 49 upregulated genes were identified in lymphovascular invasion-positive patients. Among these genes, TNFSF11, IL6ST, and EPAS1 play important roles in cytokine-receptor interaction, which is the most enriched pathway related to lymphovascular invasion. Moreover, the results also suggested that an imbalance between extracellular matrix components and tumor micro-environment could induce lymphovascular invasion. Our study evaluated the underlying mechanisms of lymphovascular invasion, which may further help to assess the risk of breast cancer progression and identify potential targets of adjuvant treatment.

  5. Reoperations after primary breast conserving surgery in women with invasive breast cancer in Catalonia, Spain: a retrospective study.

    Science.gov (United States)

    Escribà, J M; Esteban, L; Gálvez, J; Pla, M J; Melià, A; Gil-Gil, M; Clèries, R; Pareja, L; Sanz, X; Bustins, M; Borrás, J M; Ribes, J

    2017-04-01

    Although complete tumor resection is accepted as the best means to reduce recurrence, reoperations after lumpectomy are a common problem in breast cancer. The aim of this study was to assess the reoperation rates after primary breast conserving surgery in invasive breast cancer cases diagnosed in Catalonia, Spain, between 2005 and 2011 and to identify variations based on patient and tumour characteristics. Women with invasive incident breast cancer identified from the Patient's Hospital Discharge Database [174.0-174.9 codes of the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) as the primary diagnosis] and receiving primary breast conserving surgery were included in the study and were followed up to 3 and 12 months by collecting information about repeat breast cancer surgery. Reoperation rates after primary breast conserving surgery decreased from 13.0 % in 2005 to 11.7 % in 2011 at 3 months and from 14.2 % in 2005 to 12.9 % in 2011 at 12 months' follow-up. While breast conservation reoperations saw a slight, non-significant increase in the same period (from 5.7 to 7.3 % at 3 months, and from 6.0 to 7.5 % at 12 months), there was a significant decrease in radical reoperation (from 7.3 to 4.4 % at 3 months and from 8.2 to 5.4 % at 12 months). Overall, additional breast surgeries decreased among younger women. Despite the rise of breast conserving surgery, reoperation rates following initial lumpectomy in Catalonia decreased by 10 % at 3 and 12 months' follow-up, remaining low and almost unchanged. Ultimately, there was also a significant decrease in mastectomies.

  6. MRI and ultrasound evaluation of invasive lobular carcinoma of the breast after primary systemic therapy.

    Science.gov (United States)

    Mori, Miki; Tsunoda, Hiroko; Takamoto, Yayoi; Murai, Michiko; Kikuchi, Mari; Honda, Satoshi; Suzuki, Koyu; Yamauchi, Hideko

    2015-07-01

    To assess magnetic resonance imaging (MRI) and ultrasound (US) evaluation of invasive lobular carcinoma after primary systemic therapy compared to the primary surgery group. A total of 218 breasts with invasive lobular carcinoma (ILC), which were diagnosed by core needle biopsy and underwent surgery between 2004 and 2010 in St. Luke's International Hospital, were reviewed. Of these, 44 breasts received primary systemic therapy (PST) and the residual 174 breasts underwent surgery first. Before surgery, MRI and second-look US were performed. Patients whose extent of lesion from MRI and US was over 90° were recommended to receive total mastectomy. Diagnostic image evaluation was categorized from the final pathology. A negative margin of breast-conserving surgery (BCS) and mastectomy which has over 90° tumor extent in pathology were regarded as "appropriate". A positive margin of BCS was regarded as "underestimated". "Overestimation" was determined when the pathological extension was small enough for BCS although MRI and US diagnosis was over 90°. Of 44 breasts which received PST, 26 breasts received BCS as initial surgery. Of these, 14 (53.8 %) breasts were "underestimated". Of these 14, 5 breasts received additional total mastectomy. Of 174 breasts that received surgery first, 121 (69.5 %) breasts received BCS as the initial surgery. Of these, 46 (38.0 %) breasts were "underestimated" and 6 breast of these 46 received additional total mastectomy. "Underestimated" rate was similar in the two groups, but the additional total mastectomy rate was significantly higher in the PST group (p = 0.025). There were no "overestimations". The "appropriate" rate was similar between the PST (68.2 %) and surgery-first groups (73.6 %). Although 68.2 % of ILC patients were evaluated "appropriately" even after PST, higher additional total mastectomy rates should be considered when selecting the surgical procedure.

  7. Drug Helps Fight Breast Tumors Tied to 'Cancer Genes'

    Science.gov (United States)

    ... Drug Helps Fight Breast Tumors Tied to 'Cancer Genes' Lynparza may offer a new treatment for women ... with breast cancer linked to BRCA1 and BRCA2 gene mutations, according to the study. Olaparib delayed cancer ...

  8. TFF3 is a normal breast epithelial protein and is associated with differentiated phenotype in early breast cancer but predisposes to invasion and metastasis in advanced disease.

    Science.gov (United States)

    Ahmed, Ahmed R H; Griffiths, Andrew B; Tilby, Michael T; Westley, Bruce R; May, Felicity E B

    2012-03-01

    The trefoil protein TFF3 stimulates invasion and angiogenesis in vitro. To determine whether it has a role in breast tumor metastasis and angiogenesis, its levels were measured by immunohistochemistry in breast tissue with a specific monoclonal antibody raised against human TFF3. TFF3 is expressed in normal breast lobules and ducts, at higher levels in areas of fibrocystic change and papillomas, in all benign breast disease lesions, and in 89% of in situ and in 83% of invasive carcinomas. In well-differentiated tumor cells, TFF3 is concentrated at the luminal edge, whereas in poorly differentiated cells polarity is inverted and expression is directed toward the stroma. Expression was high in well-differentiated tumors and was associated significantly with low histological grade and with estrogen and progesterone receptor expression, accordant with induction of TFF3 mRNA by estrogen in breast cancer cells. Paradoxically, TFF3 expression was associated with muscle, neural, and lymphovascular invasion and the presence and number of involved lymph nodes, and it was an independent predictive marker of lymphovascular invasion and lymph node involvement. Consistent with an angiogenic function, TFF3 expression correlated strongly with microvessel density evaluated with CD31 and CD34. In conclusion, TFF3 is expressed in both the normal and diseased breast. Although associated with features of good prognosis, its profile of expression in invasive cancer is consistent with a role in breast tumor progression and tumor cell dissemination. Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  9. Choline kinase overexpression increases invasiveness and drug resistance of human breast cancer cells.

    Science.gov (United States)

    Shah, Tariq; Wildes, Flonne; Penet, Marie-France; Winnard, Paul T; Glunde, Kristine; Artemov, Dmitri; Ackerstaff, Ellen; Gimi, Barjor; Kakkad, Samata; Raman, Venu; Bhujwalla, Zaver M

    2010-07-01

    A direct correlation exists between increased choline kinase (Chk) expression, and the resulting increase of phosphocholine levels, and histological tumor grade. To better understand the function of Chk and choline phospholipid metabolism in breast cancer we have stably overexpressed one of the two isoforms of Chk-alpha known to be upregulated in malignant cells, in non-invasive MCF-7 human breast cancer cells. Dynamic tracking of cell invasion and cell metabolism were studied with a magnetic resonance (MR) compatible cell perfusion assay. The MR based invasion assay demonstrated that MCF-7 cells overexpressing Chk-alpha (MCF-7-Chk) exhibited an increase of invasion relative to control MCF-7 cells (0.84 vs 0.3). Proton MR spectroscopy studies showed significantly higher phosphocholine and elevated triglyceride signals in Chk overexpressing clones compared to control cells. A test of drug resistance in MCF-7-Chk cells revealed that these cells had an increased resistance to 5-fluorouracil and higher expression of thymidylate synthase compared to control MCF-7 cells. To further characterize increased drug resistance in these cells, we performed rhodamine-123 efflux studies to evaluate drug efflux pumps. MCF-7-Chk cells effluxed twice as much rhodamine-123 compared to MCF-7 cells. Chk-alpha overexpression resulted in MCF-7 human breast cancer cells acquiring an increasingly aggressive phenotype, supporting the role of Chk-alpha in mediating invasion and drug resistance, and the use of phosphocholine as a biomarker of aggressive breast cancers.

  10. The influence of biomechanical properties and cannabinoids on tumor invasion.

    Science.gov (United States)

    Hohmann, Tim; Grabiec, Urszula; Ghadban, Chalid; Feese, Kerstin; Dehghani, Faramarz

    2017-01-02

    Cannabinoids are known to have an anti-tumorous effect, but the underlying mechanisms are only sparsely understood. Mechanical characteristics of tumor cells represent a promising marker to distinguish between tumor cells and the healthy tissue. We tested the hypothesis whether cannabinoids influence the tumor cell specific mechanical and migratory properties and if these factors are a prognostic marker for the invasiveness of tumor cells. 3 different glioblastoma cell lines were treated with cannabinoids and changes of mechanical and migratory properties of single cells were measured using atomic force microscopy and time lapse imaging. The invasiveness of cell lines was determined using a co-culture model with organotypic hippocampal slice cultures. We found that cannabinoids are capable of influencing migratory and mechanical properties in a cell line specific manner. A network analysis revealed a correlation between a "generalized stiffness" and the invasiveness for all tumor cell lines after 3 and 4 d of invasion time: r3d = -0.88 [-0.52;-0.97]; r4d = -0.90 [-0.59;-0.98]. Here we could show that a "generalized stiffness" is a profound marker for the invasiveness of a tumor cell population in our model and thus might be of high clinical relevance for drug testing. Additionally cannabinoids were shown to be of potential use for therapeutic approaches of glioblastoma.

  11. Breast Cancer Screening in Denmark: A Cohort Study of Tumor Size and Overdiagnosis.

    Science.gov (United States)

    Jørgensen, Karsten Juhl; Gøtzsche, Peter C; Kalager, Mette; Zahl, Per-Henrik

    2017-03-07

    Effective breast cancer screening should detect early-stage cancer and prevent advanced disease. To assess the association between screening and the size of detected tumors and to estimate overdiagnosis (detection of tumors that would not become clinically relevant). Cohort study. Denmark from 1980 to 2010. Women aged 35 to 84 years. Screening programs offering biennial mammography for women aged 50 to 69 years beginning in different regions at different times. Trends in the incidence of advanced (>20 mm) and nonadvanced (≤20 mm) breast cancer tumors in screened and nonscreened women were measured. Two approaches were used to estimate the amount of overdiagnosis: comparing the incidence of advanced and nonadvanced tumors among women aged 50 to 84 years in screening and nonscreening areas; and comparing the incidence for nonadvanced tumors among women aged 35 to 49, 50 to 69, and 70 to 84 years in screening and nonscreening areas. Screening was not associated with lower incidence of advanced tumors. The incidence of nonadvanced tumors increased in the screening versus prescreening periods (incidence rate ratio, 1.49 [95% CI, 1.43 to 1.54]). The first estimation approach found that 271 invasive breast cancer tumors and 179 ductal carcinoma in situ (DCIS) lesions were overdiagnosed in 2010 (overdiagnosis rate of 24.4% [including DCIS] and 14.7% [excluding DCIS]). The second approach, which accounted for regional differences in women younger than the screening age, found that 711 invasive tumors and 180 cases of DCIS were overdiagnosed in 2010 (overdiagnosis rate of 48.3% [including DCIS] and 38.6% [excluding DCIS]). Regional differences complicate interpretation. Breast cancer screening was not associated with a reduction in the incidence of advanced cancer. It is likely that 1 in every 3 invasive tumors and cases of DCIS diagnosed in women offered screening represent overdiagnosis (incidence increase of 48.3%). None.

  12. DEGRO practical guidelines for radiotherapy of breast cancer IV. Radiotherapy following mastectomy for invasive breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Wenz, Frederik; Sperk, Elena [Universitaetsmedizin Mannheim, Klinik fuer Strahlentherapie und Radioonkologie, Mannheim (Germany); Budach, Wilfried [Heinrich-Heine-University, Duesseldorf (Germany); Dunst, Juergen [University Hospital Schleswig-Holstein, Luebeck (Germany); Feyer, Petra [Vivantes Hospital Neukoelln, Berlin (Germany); Fietkau, Rainer; Sauer, Rolf [University Hospital Erlangen, Erlangen (Germany); Haase, Wulf [Formerly St.-Vincentius-Hospital, Karlsruhe (Germany); Harms, Wolfgang [St. Clara Hospital, Basel (Switzerland); Piroth, Marc D. [Helios Hospital, Wuppertal (Germany); Sautter-Bihl, Marie-Luise [Municipal Hospital, Karlsruhe (Germany); Sedlmayer, Felix; Fussl, Christoph [Paracelsus Medical University Hospital, Salzburg (Germany); Souchon, Rainer; Collaboration: Breast Cancer Expert Panel of the German Society of Radiation Oncology (DEGRO)

    2014-08-15

    Since the last recommendations from the Breast Cancer Expert Panel of the German Society for Radiation Oncology (DEGRO) in 2008, evidence for the effectiveness of postmastectomy radiotherapy (PMRT) has grown. This growth is based on updates of the national S3 and international guidelines, as well as on new data and meta-analyses. New aspects were considered when updating the DEGRO recommendations. The authors performed a comprehensive survey of the literature. Data from recently published (meta-)analyses, randomized clinical trials and international cancer societies' guidelines yielding new aspects compared to 2008 were reviewed and discussed. New aspects were included in the current guidelines. Specific issues relating to particular PMRT constellations, such as the presence of risk factors (lymphovascular invasion, blood vessel invasion, positive lymph node ratio > 20 %, resection margins < 3 mm, G3 grading, young age/premenopausal status, extracapsular invasion, negative hormone receptor status, invasive lobular cancer, size > 2 cm or a combination of ≥ 2 risk factors) and 1-3 positive lymph nodes are emphasized. The evidence for improved overall survival and local control following PMRT for T4 tumors, positive resection margins, > 3 positive lymph nodes and in T3 N0 patients with risk factors such as lymphovascular invasion, G3 grading, close margins, and young age has increased. Recently identified risk factors such as invasive lobular subtype and negative hormone receptor status were included. For patients with 1-3 positive lymph nodes, the recommendation for PMRT has reached the 1a level of evidence. PMRT is mandatory in patients with T4 tumors and/or positive lymph nodes and/or positive resection margins. PMRT should be strongly considered in patients with T3 N0 tumors and risk factors, particularly when two or more risk factors are present. (orig.) [German] Seit der letzten Aktualisierung der 2008 publizierten Leitlinie der &apos

  13. Breast cancer associated a2 isoform vacuolar ATPase immunomodulates neutrophils: potential role in tumor progression

    Science.gov (United States)

    Ibrahim, Safaa A.; Katara, Gajendra K.; Kulshrestha, Arpita; Jaiswal, Mukesh K.; Amin, Magdy A.; Beaman, Kenneth D.

    2015-01-01

    In invasive breast cancer, tumor associated neutrophils (TAN) represent a significant portion of the tumor mass and are associated with increased angiogenesis and metastasis. Identifying the regulatory factors that control TAN behavior will help in developing ideal immunotherapies. Vacuolar ATPases (V-ATPases), multi-subunit proton pumps, are highly expressed in metastatic breast cancer cells. A cleaved peptide from a2 isoform V-ATPase (a2NTD) has immunomodulatory role in tumor microenvironment. Here, we report for the first time the role of V-ATPase in neutrophils modulation. In invasive breast cancer cells, a2NTD was detected and a2V was highly expressed on the surface. Immunohistochemical analysis of invasive breast cancer tissues revealed that increased neutrophil recruitment and blood vessel density correlated with increased a2NTD levels. In order to determine the direct regulatory role of a2NTD on neutrophils, recombinant a2NTD was used for the treatment of neutrophils isolated from the peripheral blood of healthy volunteers. Neutrophils treated with a2NTD (a2Neuɸ) showed increased secretion of IL-1RA, IL-10, CCL-2 and IL-6 that are important mediators in cancer related inflammation. Moreover, a2Neuɸ exhibited an increased production of protumorigenic factors including IL-8, matrix metaloprotinase-9 and vascular endothelial growth factor. Further, functional characterization of a2Neuɸ revealed that a2Neuɸ derived products induce in vitro angiogenesis as well as increase the invasiveness of breast cancer cells. This study establishes the modulatory effect of breast cancer associated a2V on neutrophils, by the action of a2NTD, which has a positive impact on tumor progression, supporting that a2V can be a potential selective target for breast cancer therapy. PMID:26460736

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

    Energy Technology Data Exchange (ETDEWEB)

    Erez, Neta, E-mail: netaerez@post.tau.ac.il [Department of Pathology, Sackler School of Medicine, Tel Aviv University, Tel-Aviv 69978 (Israel); Glanz, Sarah [Department of Pathology, Sackler School of Medicine, Tel Aviv University, Tel-Aviv 69978 (Israel); Raz, Yael [Department of Pathology, Sackler School of Medicine, Tel Aviv University, Tel-Aviv 69978 (Israel); Department of Obstetrics and Gynecology, LIS Maternity Hospital, Tel Aviv Sourasky Medical Center, affiliated with Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv (Israel); Avivi, Camilla [Department of Pathology, Sheba Medical Center, Tel Hashomer, affiliated with Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv (Israel); Barshack, Iris [Department of Pathology, Sackler School of Medicine, Tel Aviv University, Tel-Aviv 69978 (Israel); Department of Pathology, Sheba Medical Center, Tel Hashomer, affiliated with Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv (Israel)

    2013-08-02

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

  15. RKIP regulates CCL5 expression to inhibit breast cancer invasion and metastasis by controlling macrophage infiltration.

    Science.gov (United States)

    Datar, Ila; Qiu, Xiaoliang; Ma, Hong Zhi; Yeung, Miranda; Aras, Shweta; de la Serna, Ivana; Al-Mulla, Fahd; Thiery, Jean Paul; Trumbly, Robert; Fan, Xuan; Cui, Hongjuan; Yeung, Kam C

    2015-11-17

    Accumulating evidence suggests that presence of macrophages in the tumor microenvironment add to the invasive and tumor-promoting hallmarks of cancer cells by secreting angiogenic and growth factors. RKIP is a known metastasis suppressor and interferes with several steps of metastasis. However, the mechanistic underpinnings of its function as a broad metastasis suppressor remain poorly understood. Here, we establish a novel pathway for RKIP regulation of metastasis inhibition through the negative regulation of RANTES/CCL5 thereby limiting tumor macrophage infiltration and inhibition of angiogenesis. Using a combination of loss- and gain-of- function approaches, we show that RKIP hinders breast cancer cell invasion by inhibiting expression of the CC chemokine CCL5 in vitro. We also show that the expression levels of RKIP and CCL5 are inversely correlated among clinical human breast cancer samples. Using a mouse allograft breast cancer transplantation model, we highlight that ectopic expression of RKIP significantly decreases tumor vasculature, macrophage infiltration and lung metastases. Mechanistically, we demonstrate that the inhibition of the CCL5 expression is the cause of the observed effects resulting from RKIP expression. Taken together, our results underscore the significance of RKIP as important negative regulator of tumor microenvironment.

  16. CCL20 promotes migration and invasiveness of human cancerous breast epithelial cells in primary culture.

    Science.gov (United States)

    Muscella, Antonella; Vetrugno, Carla; Marsigliante, Santo

    2017-11-01

    The relation between the tumor and its microenvironment is one of the most interesting and less understood issues. Recently, we showed a role of CCL20 chemokine in proning the healthy tissue neighboring the tumor to carcinogenesis. Besides, tumor-secreted CCL20 induced proliferation, migration, and EMT of healthy cells. In this context, we have studied here if CCL20 had effects on the migration of cancer cells and the intracellular pathways used in breast epithelial cells in primary culture. Using molecular (siRNA) and pharmacological (inhibitors) techniques, we found multiple signaling kinases to be activated and involved in CCL20-induced tumor breast cell migration. CCL20 provoked a 2.5-fold increase of cell migration and invasion; CCL20 also enhanced MMP- 2 and MMP-9 mRNAs/protein expression and activities. Cell migration and invasiveness due to CCL20 significantly decreased when MMP-2 and MMP-9 were inhibited in CCL20-stimulated cells. CCL20 controlled MMP-2 expression through the JAK2/STAT3 pathway, while the expression of MMP-9 occurred by PKC-α that activated, consequently, c-Src, Akt, and finally NF-kB. These results reveal a role for CCL20 also in tumor breast cell and point to CCL20 as a novel therapeutic target in cancer. © 2017 Wiley Periodicals, Inc.

  17. Shigella mediated depletion of macrophages in a murine breast cancer model is associated with tumor regression.

    Directory of Open Access Journals (Sweden)

    Katharina Galmbacher

    Full Text Available A tumor promoting role of macrophages has been described for a transgenic murine breast cancer model. In this model tumor-associated macrophages (TAMs represent a major component of the leukocytic infiltrate and are associated with tumor progression. Shigella flexneri is a bacterial pathogen known to specificly induce apotosis in macrophages. To evaluate whether Shigella-induced removal of macrophages may be sufficient for achieving tumor regression we have developed an attenuated strain of S. flexneri (M90TDeltaaroA and infected tumor bearing mice. Two mouse models were employed, xenotransplantation of a murine breast cancer cell line and spontanous breast cancer development in MMTV-HER2 transgenic mice. Quantitative analysis of bacterial tumor targeting demonstrated that attenuated, invasive Shigella flexneri primarily infected TAMs after systemic administration. A single i.v. injection of invasive M90TDeltaaroA resulted in caspase-1 dependent apoptosis of TAMs followed by a 74% reduction in tumors of transgenic MMTV-HER-2 mice 7 days post infection. TAM depletion was sustained and associated with complete tumor regression.These data support TAMs as useful targets for antitumor therapy and highlight attenuated bacterial pathogens as potential tools.

  18. Preoperative MRI features associated with lymphovascular invasion in node-negative invasive breast cancer: A propensity-matched analysis.

    Science.gov (United States)

    Cheon, Hyejin; Kim, Hye Jung; Lee, So Mi; Cho, Seung Hyun; Shin, Kyung Min; Kim, Gab Chul; Park, Ji Young; Kim, Won Hwa

    2017-10-01

    In node-negative disease, the presence of lymphovascular invasion (LVI) is reported to be an unfavorable prognostic factor. Thus, the aim of this study was to evaluate whether preoperative breast MRI features are associated with LVI in patients with node-negative invasive breast cancer by a propensity-matched analysis. Among 389 patients with node-negative invasive ductal breast cancer who had preoperative breast 3.0 Tesla MRI with precontrast T2-weighted fat-suppressed, pre- and dynamic postcontrast T1-weighted fat-suppressed sequences, 61 patients with LVI (LVI group) were matched with 183 patients without LVI (no LVI group) at a ratio of 1:3 in terms of age, histologic grade, tumor size, and hormone receptor status. Two radiologists reviewed the MRI features, following profiles of focal breast edema (peritumoral, prepectoral, subcutaneous), intratumoral T2 signal intensity, adjacent vessel sign, and increased ipsilateral whole-breast vascularity, in addition to 2013 Breast Imaging Reporting and Data System lexicon. The presence of peritumoral edema (45.9% [28/61] versus 30.6% [56/183], P = 0.030) and adjacent vessel sign (82.0% [50/61] versus 68.3% [125/183], P = 0.041) was significantly associated with LVI. Prepectoral edema was also more frequently observed in the LVI group than in the no LVI group with borderline significance (26.2% [16/61] versus 15.3% [28/183], P = 0.055). In cases of nonmass enhancement, regional enhancement was more frequently found in the LVI group than in the no LVI group (60.0% [3/4] versus 5.9% [1/4], P = 0.042). Preoperative breast MRI features may be associated with LVI in patients with node-negative invasive breast cancer. 3 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2017;46:1037-1044. © 2017 International Society for Magnetic Resonance in Medicine.

  19. Magnetic resonance imaging of invasive breast cancer

    African Journals Online (AJOL)

    G5

    graphic findings, and screening for breast cancer in younger women with familial breast cancer. Interpretation of MR images requires a meticulous imaging technique including the use of contrast enhancement and fat suppression MR sequences using a good breast coil. Introduction. The role of MR imaging in the diagno-.

  20. Immunophenotyping invasive breast cancer: paving the road for molecular imaging.

    OpenAIRE

    Vermeulen, J.F.; Brussel, A.S. van; Groep, P. van der; Morsink, F.H.; Bult, P.; Wall, E. van der; Diest, P.J. van

    2012-01-01

    Abstract Background Mammographic population screening in The Netherlands has increased the number of breast cancer patients with small and non-palpable breast tumors. Nevertheless, mammography is not ultimately sensitive and specific for distinct subtypes. Molecular imaging with targeted tracers might increase specificity and sensitivity of detection. Because development of new tracers is labor-intensive and costly, we searched for the smallest panel of tumor membrane markers that would allow...

  1. Tamoxifen inhibits ER-negative breast cancer cell invasion and metastasis by accelerating Twist1 degradation.

    Science.gov (United States)

    Ma, Gang; He, Jianjun; Yu, Yang; Xu, Yixiang; Yu, Xiaobin; Martinez, Jarrod; Lonard, David M; Xu, Jianming

    2015-01-01

    Twist1 is a transcription factor driving epithelial-mesenchymal transition, invasion and metastasis of breast cancer cells. Mice with germ-line Twist1 knockout are embryonic lethal, while adult mice with inducible Twist1 knockout have no obvious health problems, suggesting that Twist1 is a viable therapeutic target for the inhibition of invasion and metastasis of breast cancer in adult patients. In this study, we expressed a luciferase protein or a Twist1-luciferase fusion protein in HeLa cells as part of a high throughput system to screen 1280 compounds in the Library of Pharmacologically Active Compounds (LOPAC) from Sigma-Aldrich for their effects on Twist1 protein expression. One of the most interesting compounds identified is tamoxifen, a selective estrogen receptor (ER) modulator used to treat ER-positive breast cancer. Tamoxifen treatment significantly accelerated Twist1 degradation in multiple cell lines including HEK293 human kidney cells, 4T1 and 168FARN mouse mammary tumor cells with either ectopically or endogenously expressed Twist1. Tamoxifen-induced Twist1 degradation could be blocked by the MG132 proteasome inhibitor, suggesting that tamoxifen induces Twist1 degradation through the ubiquitination-proteasome pathway. However, tamoxifen-induced Twist1 degradation was independent of Twist1 mRNA expression, estrogen signaling and MAPK-mediated Twist1 phosphorylation in these cells. Importantly, tamoxifen also significantly inhibited invasive behavior in Matrigel and lung metastasis in SCID-bg mice of ER-negative 4T1 mammary tumor cells, which depend on endogenous Twist1 to invade and metastasize. These results indicate that tamoxifen can significantly accelerate Twist1 degradation to suppress cancer cell invasion and metastasis, suggesting that tamoxifen can be used not only to treat ER-positive breast cancers but also to reduce Twist1-mediated invasion and metastasis in ER-negative breast cancers.

  2. Correlation between 3T apparent diffusion coefficient values and grading of invasive breast carcinoma.

    Science.gov (United States)

    Cipolla, Valentina; Santucci, Domiziana; Guerrieri, Daniele; Drudi, Francesco Maria; Meggiorini, Maria Letizia; de Felice, Carlo

    2014-12-01

    The aim of this study was to evaluate whether the apparent diffusion coefficient (ADC) provided by 3.0T (3T) magnetic resonance diffusion-weighted imaging (DWI) varied according to the grading of invasive breast carcinoma. A total of 92 patients with 96 invasive breast cancer lesions were enrolled; all had undergone 3T magnetic resonance imaging (MRI) for local staging. All lesions were confirmed by histological analysis, and tumor grade was established according to the Nottingham Grading System (NGS). MRI included both dynamic contrast-enhanced and DWI sequences, and ADC value was calculated for each lesion. ADC values were compared with NGS classification using the Mann-Whitney U and the Kruskal-Wallis H tests. Grading was considered as a comprehensive prognostic factor, and Rho Spearman test was performed to determine correlation between grading and tumor size, hormonal receptor status, HER2 expression and Ki67 index. Pearson's Chi square test was carried out to compare grading with the other prognostic factors. ADC values were significantly higher in G1 than in G3 tumors. No significant difference was observed when G1 and G3 were compared with G2. Tumor size, hormonal receptor status, HER2 expression and Ki67 index correlated significantly with grading but there was a significant difference only between G1 and G3 related to the ER and PR status, HER2 expression and Ki67 index. There was no statistically significant difference in lesion size between the two groups. ADC values obtained on 3T DWI correlated with low-grade (G1) and high-grade (G3) invasive breast carcinoma. 3T ADC may be a helpful tool for identifying high-grade invasive breast carcinoma. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  3. Association between Parenchymal Enhancement of the Contralateral Breast in Dynamic Contrast-enhanced MR Imaging and Outcome of Patients with Unilateral Invasive Breast Cancer.

    Science.gov (United States)

    van der Velden, Bas H M; Dmitriev, Ivan; Loo, Claudette E; Pijnappel, Ruud M; Gilhuijs, Kenneth G A

    2015-09-01

    To retrospectively investigate whether parenchymal enhancement in dynamic contrast material-enhanced magnetic resonance (MR) imaging of the contralateral breast in patients with unilateral invasive breast cancer is associated with therapy outcome. After obtaining approval of the institutional review board and patients' written informed consent, 531 women with unilateral invasive breast cancer underwent dynamic contrast-enhanced MR imaging between 2000 and 2008. The contralateral parenchyma was segmented automatically, in which the mean of the top 10% late enhancement was calculated. Cox regression was used to test associations between parenchymal enhancement, patient and tumor characteristics, and overall survival and invasive disease-free survival. Subset analyses were performed and stratified according to immunohistochemical subtypes and type of adjuvant treatment received. Median follow-up was 86 months. Age (P breast cancer (n = 398), age (P images (P = .049), and parenchymal enhancement (P = .011) were significant. In patients who underwent endocrine therapy (n = 174), parenchymal enhancement was the only significant covariate for overall survival and invasive disease-free survival (P enhancement in the contralateral breast of patients with invasive unilateral breast cancer is significantly associated with long-term outcome, particularly in patients with estrogen receptor-positive, human epidermal growth factor receptor 2-negative breast cancer. Lower value of the mean top 10% enhancement of the parenchyma shows potential as a predictive biomarker for relatively poor outcome in patients who undergo endocrine therapy. These results should, however, be validated in a larger study.

  4. Tensile Forces Originating from Cancer Spheroids Facilitate Tumor Invasion.

    Directory of Open Access Journals (Sweden)

    Katarzyna S Kopanska

    Full Text Available The mechanical properties of tumors and the tumor environment provide important information for the progression and characterization of cancer. Tumors are surrounded by an extracellular matrix (ECM dominated by collagen I. The geometrical and mechanical properties of the ECM play an important role for the initial step in the formation of metastasis, presented by the migration of malignant cells towards new settlements as well as the vascular and lymphatic system. The extent of this cell invasion into the ECM is a key medical marker for cancer prognosis. In vivo studies reveal an increased stiffness and different architecture of tumor tissue when compared to its healthy counterparts. The observed parallel collagen organization on the tumor border and radial arrangement at the invasion zone has raised the question about the mechanisms organizing these structures. Here we study the effect of contractile forces originated from model tumor spheroids embedded in a biomimetic collagen I matrix. We show that contractile forces act immediately after seeding and deform the ECM, thus leading to tensile radial forces within the matrix. Relaxation of this tension via cutting the collagen does reduce invasion, showing a mechanical relation between the tensile state of the ECM and invasion. In turn, these results suggest that tensile forces in the ECM facilitate invasion. Furthermore, simultaneous contraction of the ECM and tumor growth leads to the condensation and reorientation of the collagen at the spheroid's surface. We propose a tension-based model to explain the collagen organization and the onset of invasion by forces originating from the tumor.

  5. Immune Escape in Breast Cancer During In Situ to Invasive Carcinoma Transition.

    Science.gov (United States)

    Gil Del Alcazar, Carlos R; Huh, Sung Jin; Ekram, Muhammad B; Trinh, Anne; Liu, Lin L; Beca, Francisco; Zi, Xiaoyuan; Kwak, Minsuk; Bergholtz, Helga; Su, Ying; Ding, Lina; Russnes, Hege G; Richardson, Andrea L; Babski, Kirsten; Min Hui Kim, Elizabeth; McDonnell, Charles H; Wagner, Jon; Rowberry, Ron; Freeman, Gordon J; Dillon, Deborah; Sorlie, Therese; Coussens, Lisa M; Garber, Judy E; Fan, Rong; Bobolis, Kristie; Allred, D Craig; Jeong, Joon; Park, So Yeon; Michor, Franziska; Polyak, Kornelia

    2017-10-01

    To investigate immune escape during breast tumor progression, we analyzed the composition of leukocytes in normal breast tissues, ductal carcinoma in situ (DCIS), and invasive ductal carcinomas (IDC). We found significant tissue and tumor subtype-specific differences in multiple cell types including T cells and neutrophils. Gene expression profiling of CD45+CD3+ T cells demonstrated a decrease in CD8+ signatures in IDCs. Immunofluorescence analysis showed fewer activated GZMB+CD8+ T cells in IDC than in DCIS, including in matched DCIS and recurrent IDC. T-cell receptor clonotype diversity was significantly higher in DCIS than in IDCs. Immune checkpoint protein TIGIT-expressing T cells were more frequent in DCIS, whereas high PD-L1 expression and amplification of CD274 (encoding PD-L1) was only detected in triple-negative IDCs. Coamplification of a 17q12 chemokine cluster with ERBB2 subdivided HER2+ breast tumors into immunologically and clinically distinct subtypes. Our results show coevolution of cancer cells and the immune microenvironment during tumor progression.Significance: The design of effective cancer immunotherapies requires the understanding of mechanisms underlying immune escape during tumor progression. Here we demonstrate a switch to a less active tumor immune environment during the in situ to invasive breast carcinoma transition, and identify immune regulators and genomic alterations that shape tumor evolution. Cancer Discov; 7(10); 1098-115. ©2017 AACR.See related commentary by Speiser and Verdeil, p. 1062This article is highlighted in the In This Issue feature, p. 1047. ©2017 American Association for Cancer Research.

  6. Relative effectiveness of adjuvant chemotherapy for invasive lobular compared with invasive ductal carcinoma of the breast.

    Science.gov (United States)

    Marmor, Schelomo; Hui, Jane Yuet Ching; Huang, Jing Li; Kizy, Scott; Beckwith, Heather; Blaes, Anne H; Rueth, Natasha M; Tuttle, Todd M

    2017-08-15

    Invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) have distinct clinical, pathologic, and genomic characteristics. The objective of the current study was to compare the relative impact of adjuvant chemotherapy on the survival of patients with ILC versus those with IDC. Women with estrogen receptor (ER)-positive, human epidermal growth factor receptor 1 (HER2) -negative, stage I/II IDC and ILC who received endocrine therapy were identified from the 2000 to 2014 California Cancer Registry. Patient, tumor, and treatment characteristics were collected. Ten-year overall survival (OS) was estimated using the Kaplan-Meier method and Cox proportional-hazards modeling. In total, 32,997 women with IDC and 4638 with ILC were identified. The receipt of chemotherapy significantly decreased during the study for both subtypes. For patients with IDC, the 10-year OS rate was 95% among those who received endocrine therapy alone versus 93% (P chemotherapy. For patients with ILC, the 10-year OS rate was 94% among those who received endocrine therapy alone versus 92% (P chemotherapy. After adjusting for patient and treatment factors, adjuvant chemotherapy was significantly associated with a decreased 10-year hazard of death for patients with IDC (hazard ratio, 0.83; 95% confidence interval, 0.74-0.92). In contrast, adjuvant chemotherapy was not independently associated with the adjusted 10-year hazard of death for patients with ILC (hazard ratio, 1.14; 95% confidence interval, 0.90-1.46). Adjuvant chemotherapy was not associated with improved OS for patients with ER-positive, HER2-negative, stage I/II ILC. Avoidance of ineffective chemotherapy will markedly reduce the adverse effects and economic burden of breast cancer treatment for a large proportion of patients with breast cancer. Cancer 2017;123:3015-21. © 2017 American Cancer Society. © 2017 American Cancer Society.

  7. The expression of prostate-specific antigen in invasive breast carcinoma and its relationship with routine clinicopathologic parameters

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    Fereshteh Mohammadizadeh

    2012-01-01

    Full Text Available Background: Invasive breast carcinoma is one of the most common cancers of women. Parameters such as lymph node status, tumor grade, and the status of hormone receptors are among the main prognostic determinants of this cancer. Immunohistochemical detection of prostate-specific antigen (PSA is widely used to identify metastatic prostatic adenocarcinoma. However, its immunoreactivity has been found in some non-prostatic tissues. This study was conducted to assess PSA expression in invasive breast carcinoma and its relationship with routine clinicopathologic parameters. Materials and Methods: 100 formalin-fixed and paraffin-embedded invasive breast carcinoma tissue specimens from the pathology archive of Alzahra hospital (Isfahan, Iran were studied for the expression of estrogen receptor (ER, progesterone receptor (PR, HER2/neu, and PSA by immunohistochemistry. Stained sections were classified according to the intensity of staining and the percentage of cells showing PSA staining. The relationship between PSA expression and other markers, age, lymph node status, tumor subtype, and tumor grade was then studied. Results: No association was found between PSA expression on one hand and PR, Her2/neu, age, lymph node status, tumor grade, and tumor subtype on the other. PSA score was reversely correlated with ER expression (P = 0.015. Conclusion: Despite the reverse relationship between PSA expression and the immunoreactivity of ER, PSA expression was not correlated with other prognostic factors. Therefore, the detection of PSA by immunohistochemistry does not seem to be a significant prognostic parameter in patients with invasive breast carcinoma.

  8. Myoferlin depletion in breast cancer cells promotes mesenchymal to epithelial shape change and stalls invasion.

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    Ruth Li

    Full Text Available Myoferlin (MYOF is a mammalian ferlin protein with homology to ancestral Fer-1, a nematode protein that regulates spermatic membrane fusion, which underlies the amoeboid-like movements of its sperm. Studies in muscle and endothelial cells have reported on the role of myoferlin in membrane repair, endocytosis, myoblast fusion, and the proper expression of various plasma membrane receptors. In this study, using an in vitro human breast cancer cell model, we demonstrate that myoferlin is abundantly expressed in invasive breast tumor cells. Depletion of MYOF using lentiviral-driven shRNA expression revealed that MDA-MB-231 cells reverted to an epithelial morphology, suggesting at least some features of mesenchymal to epithelial transition (MET. These observations were confirmed by the down-regulation of some mesenchymal cell markers (e.g., fibronectin and vimentin and coordinate up-regulation of the E-cadherin epithelial marker. Cell invasion assays using Boyden chambers showed that loss of MYOF led to a significant diminution in invasion through Matrigel or type I collagen, while cell migration was unaffected. PCR array and screening of serum-free culture supernatants from shRNA(MYOF transduced MDA-MB-231 cells indicated a significant reduction in the steady-state levels of several matrix metalloproteinases. These data when considered in toto suggest a novel role of MYOF in breast tumor cell invasion and a potential reversion to an epithelial phenotype upon loss of MYOF.

  9. Pancreatic metastasis from invasive pleomorphic lobular carcinoma of the breast: a rare case report.

    Science.gov (United States)

    Sun, Xiangjie; Zuo, Ke; Huang, Dan; Yu, Baohua; Cheng, Yufan; Yang, Wentao

    2017-07-11

    Invasive pleomorphic lobular carcinoma (PLC) is an aggressive subtype of invasive lobular carcinoma of the breast, which has its own histopathological and biological features. The metastatic patterns for PLC are distinct from those of invasive ductal carcinoma. In addition, pancreatic metastasis from PLC is extremely rare. We report a rare case of a 48-year-old woman presenting with clinical gastrointestinal symptoms and pancreatic metastasis of PLC. The pancreatic tumor was composed of pleomorphic tumor cells arranged in the form of solid sheets and nests and as single files, with frequent mitotic figures, nucleolar prominence, high nuclear to cytoplasmic ratio and loss of cohesion. The malignant cells were positive for p120 (cytoplasmic) and GATA3 and negative for estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, E-cadherin, gross cystic disease fluid protein 15 and mammaglobin, which indicated a lobular carcinoma phenotype of the breast. To the best of our knowledge, this is one of the few reported cases in the literature of pancreatic metastasis of invasive lobular carcinoma of the breast, of which the definitive diagnosis was obtained only after surgery. Rare metastasis sites should be considered, particularly, when a patient has a medical history of PLC.

  10. ASPN and GJB2 Are Implicated in the Mechanisms of Invasion of Ductal Breast Carcinomas

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    Bàrbara Castellana, Daniel Escuin, Gloria Peiró, Bárbara Garcia-Valdecasas, Tania Vázquez, Cristina Pons, Maitane Pérez-Olabarria, Agustí Barnadas, Enrique Lerma

    2012-01-01

    Full Text Available The mechanism of progression from ductal carcinoma in situ (DCIS to invasive ductal carcinoma (IDC remains largely unknown. We compared gene expression in tumors with simultaneous DCIS and IDC to decipher how diverse proteins participate in the local invasive process.Twenty frozen tumor specimens with concurrent, but separated, DCIS and IDC were microdissected and evaluated. Total RNA was extracted and microarray analysis was performed using Affymetrix GeneChip® Human Gene 1.0 ST Arrays. Microarray data were validated by quantitative real time reverse transcription-PCR (qRT-PCR and immunohistochemistry. Controls included seven pure in situ carcinomas, eight fragments from normal breast tissue, and a series of mouse breast carcinomas (MMTV-PyMT.Fifty-six genes were differentially expressed between DCIS and IDC samples. The genes upregulated in IDC samples, and probably associated with invasion, were related to the epithelial-mesenchymal transition (ASPN, THBS2, FN1, SPARC, and COL11A1, cellular adhesion (GJB2, cell motility and progression (PLAUR, PLAU, BGN, ADAMTS16, and ENPP2, extracellular matrix degradation (MMP11, MMP13, and MMP14, and growth/proliferation (ST6GAL2. qRT-PCR confirmed the expression patterns of ASPN, GJB2, ENPP2, ST6GAL2, and TMBS10. Expression of the ASPN and GJB2 gene products was detected by immunohistochemistry in invasive carcinoma foci. The association of GJB2 protein expression with invasion was confirmed by qRT-PCR in mouse tumors (P < 0.05.Conclusions: The upregulation of ASPN and GJB2 may play important roles in local invasion of breast ductal carcinomas.

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

    Science.gov (United States)

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

    2018-01-01

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

  12. The pattern of invasive lobular carcinoma in the patients diagnosed with breast cancer from Balochistan.

    Science.gov (United States)

    Baloch, A H; Khosa, A N; Bangulzai, N; Sadia, H; Ahmed, M; Khan, F; Jan, M; Tareen, M; Kakar, M H; Shuja, J; Naseeb, H K; Ahmad, J

    2016-01-01

    Invasive lobular carcinoma (ILC) is the second most common type of breast cancer accounting for 5%-15% of all the breast cancer cases. The present study was performed on 171 breast cancer patients from Balochistan registered in CENAR (Center for Nuclear Medicine and Radiotherapy), Quetta. Written consent was obtained from the patients. The history of the disease was taken from the patients, and the patients' enrollment files were retrieved. Of the 171 patients, 5 (2.96%) were diagnosed with ILC with tumor Grade II, and stage of the cancer reported was Grade III in all the 5 patients affected with ILC. ILC is the second most common type of breast cancer diagnosed with comparatively lower grade but almost reported infiltrating.

  13. Tramadol inhibits proliferation, migration and invasion via α2-adrenoceptor signaling in breast cancer cells.

    Science.gov (United States)

    Xia, M; Tong, J-H; Zhou, Z-Q; Duan, M-L; Xu, J-G; Zeng, H-J; Wang, S-H

    2016-01-01

    The aim of this study was to examine the function of tramadol on cell proliferation, migration and invasion in breast cancer cells in vitro, and to evaluate the effect of tramadol in vivo. Further, we explore the mechanism accounting for the role of tramadol on breast cancer cells. Cell proliferation was detected by the methyl thiazolyl tetrazolium (MTT) assay. Wound healing assay and transwell assay was applied to quantify the migration and invasion ability of MDA-MB-231 cells. The expression of endogenous α2-adrenoceptor and ERK was measured by Western blotting. Tramadol at a clinical dose of up to 2 μM significantly inhibited the proliferation, migration and invasion in a time-dependent manner from day 0 to 28 in vitro. Moreover, tramadol suppressed the growth of xenotransplant tumor in vivo markedly. Furthermore, the protein levels of α2-adrenoceptor and phosphorylated ERK were decreased by tramadol, whereas the expression of total ERK remained unchanged. In addition, downregulation of α2-adrenoceptor by yohimbine could mimic the effect of tramadol treatment. Collectively, we demonstrated that tramadol could inhibit proliferation, migration and invasion of breast cancers via inactivating α2-adrenoceptor signaling pathway. Our data provide the experimental fundamental for further investigation of the anti-cancer effect of tramadol in breast cancer cells.

  14. Expression of melatonin receptor MT1 in cells of human invasive ductal breast carcinoma.

    Science.gov (United States)

    Jablonska, Karolina; Pula, Bartosz; Zemla, Agata; Owczarek, Tomasz; Wojnar, Andrzej; Rys, Janusz; Ambicka, Aleksandra; Podhorska-Okolow, Marzena; Ugorski, Maciej; Dziegiel, Piotr

    2013-04-01

    In humans, two main types of membrane melatonin receptors have been identified, MT1 and MT2. Expression of MT1 in neoplastic cells seems to increase the efficacy of melatonin's oncostatic activity. The purpose of this study was to determine the distribution and the intensity of MT1 expression in breast cancer cells and to correlate it with clinicopathological factors. Immunohistochemical studies (IHC) were conducted on 190 cases of invasive ductal breast carcinomas (IDC) and molecular studies were performed on 29 cases of frozen tumor fragments and selected breast cancer cell lines. Most of the studied tumors manifested a membranous/cytoplasmic IHC expression of MT1. In IDC, the MT1 expression was higher than in fibrocystic breast disease. MT1 expression was higher in estrogen receptor positive (ER+) and HER2 positive (HER2+) tumors. Triple negative tumors (TN) manifested the lowest MT1 expression level. The lowest MT1 protein expression level was noted in the TN breast cancer cell line MDA-MB-231 compared with ER+ cell lines MCF-7 and SK-BR-3. MT1 mRNA expression was negatively correlated with the malignancy grade of the studied IDC cases. Moreover, higher MT1 expression was associated with patients' longer overall survival (OS) in the group of ER+ breast cancers and treated with tamoxifen. Multivariate analysis indicated that MT1 was an independent prognostic factor in the ER+ tumors for OS and event-free survival in the ER+ tumors. The results of this study may point to a potential prognostic and therapeutic significance of MT1 in IDC. © 2013 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.

  15. Invasive lobular breast cancer and its variants: how special are they for systemic therapy decisions?

    Science.gov (United States)

    Guiu, Séverine; Wolfer, Anita; Jacot, William; Fumoleau, Pierre; Romieu, Gilles; Bonnetain, Franck; Fiche, Maryse

    2014-12-01

    The WHO classification of breast tumors distinguishes, besides invasive breast cancer 'of no special type' (former invasive ductal carcinoma, representing 60-70% of all breast cancers), 30 special types, of which invasive lobular carcinoma (ILC) is the most common (5-15%). We review the literature on (i) the specificity and heterogeneity of ILC biology as documented by various analytical techniques, including the results of molecular testing for risk of recurrence; (ii) the impact of lobular histology on prediction of prognosis and effect of systemic therapies in patients. Though it is generally admitted that ILC has a better prognosis than IDC, is endocrine responsive, and responds poorly to chemotherapy, currently available data do not unanimously support these assumptions. This review demonstrates some lack of specific data and a need for improving clinical research design to allow oncologists to make informed systemic therapy decisions in patients with ILC. Importantly, future studies should compare various endpoints in ILC breast cancer patients among the group of hormonosensitive breast cancer. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  16. Invasive ductal carcinoma within borderline phyllodes tumor with lymph node metastases: A case report and review of the literature

    Science.gov (United States)

    WU, DI; ZHANG, HAIPENG; GUO, LIANG; YAN, XU; FAN, ZHIMIN

    2016-01-01

    Phyllodes tumor (PT) is a rare type of biphasic fibroepithelial neoplasm that may coexist with a breast tumor in rare cases. In the current study, a 52-year-old female presented with a left breast lump. Mammography and sonographic examination results suggested a diagnosis of malignant tumor. Histological analysis revealed a borderline PT with invasive ductal carcinoma (IDC) within the tumor. Due to the presence of a single micrometastasis in three of the sentinel lymph nodes, the patient underwent modified radical mastectomy. The excised tumor contained triple negative breast cancer; therefore, postoperative treatment included six cycles of chemotherapy and 25 cycles of radiotherapy. The patient exhibited no recurrence and no metastatic disease at the 23-month follow-up examination. Thus, the present study discussed the case of a female patient that presented with IDC within borderline PT and reviewed the literature on this rare type of neoplasm. Various types of breast carcinoma have been identified to coexist with PT in different masses; however, no standard therapeutic regimen has been established for the coexistence of PT and breast cancer in the same mass. The present study indicates that determination of an appropriate treatment strategy predominantly depends on the characteristics of the individual breast tumor. PMID:27073506

  17. Predicting invasive breast cancer versus DCIS in different age groups.

    Science.gov (United States)

    Ayvaci, Mehmet U S; Alagoz, Oguzhan; Chhatwal, Jagpreet; Munoz del Rio, Alejandro; Sickles, Edward A; Nassif, Houssam; Kerlikowske, Karla; Burnside, Elizabeth S

    2014-08-11

    Increasing focus on potentially unnecessary diagnosis and treatment of certain breast cancers prompted our investigation of whether clinical and mammographic features predictive of invasive breast cancer versus ductal carcinoma in situ (DCIS) differ by age. We analyzed 1,475 malignant breast biopsies, 1,063 invasive and 412 DCIS, from 35,871 prospectively collected consecutive diagnostic mammograms interpreted at University of California, San Francisco between 1/6/1997 and 6/29/2007. We constructed three logistic regression models to predict the probability of invasive cancer versus DCIS for the following groups: women ≥ 65 (older group), women 50-64 (middle age group), and women group). We identified significant predictors and measured the performance in all models using area under the receiver operating characteristic curve (AUC). The models for older and the middle age groups performed significantly better than the model for younger group (AUC = 0.848 vs, 0.778; p = 0.049 and AUC = 0.851 vs, 0.778; p = 0.022, respectively). Palpability and principal mammographic finding were significant predictors in distinguishing invasive from DCIS in all age groups. Family history of breast cancer, mass shape and mass margins were significant positive predictors of invasive cancer in the older group whereas calcification distribution was a negative predictor of invasive cancer (i.e. predicted DCIS). In the middle age group--mass margins, and in the younger group--mass size were positive predictors of invasive cancer. Clinical and mammographic finding features predict invasive breast cancer versus DCIS better in older women than younger women. Specific predictive variables differ based on age.

  18. Invasive lobular carcinoma of the male breast – a systematic review with an illustrative case study

    Directory of Open Access Journals (Sweden)

    Senger JL

    2017-05-01

    Full Text Available Jenna-Lynn Senger,1 Scott J Adams,2 Rani Kanthan3 1Division of Plastic Surgery, University of Alberta, Edmonton, AB, Canada; 2College of Medicine, 3Department of Pathology and Laboratory Medicine, University of Saskatchewan, Saskatoon, SK, Canada Abstract: Male breast cancer is rare, comprising only 1% of all mammary cancers; invasive ductal carcinoma is by far the commonest subtype in both men and women. Though lobular breast cancer is the second most common subtype seen in women, such cancers are extremely uncommon in men, and this is likely related to the lack of lobular development in the male breast. Thus, due to the rarity of this subtype among breast cancers, compounded by the overall rarity of breast cancer in men, current understanding of the pathogenesis of this disease and its management is largely derived from case series and extrapolation of information from the larger cohort of female patients. This paper provides a systematic review on invasive lobular carcinoma of the male breast in the context of an illustrative case study. A comprehensive analysis of the National Cancer Institute’s Surveillance, Epidemiology, and End Results Data 1973–2013 leading to an exploration of the pathogenesis, epidemiology, clinical presentation, diagnosis, tumor characteristics, and management of lobular breast carcinoma in men is also discussed. Lobular subtype of breast cancer remains an enigmatic elusive disease that needs additional research to unravel its overall pathogenesis and molecular profile to provide insight for improved therapeutic management options. Keywords: male breast cancer, lobular breast carcinoma, e-cadherin

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

    Science.gov (United States)

    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 Plobular 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 between ER+ lobular and ER+ IDC tumors. These data provide evidence for overlapping, but distinct etiological pathways within ER+ breast cancer between morphological subtypes.

  20. The effect of fibrillar matrix architecture on tumor cell invasion of physically challenging environments.

    Science.gov (United States)

    Guzman, Asja; Ziperstein, Michelle J; Kaufman, Laura J

    2014-08-01

    Local invasion by and dissemination of cancer cells from a primary tumor are key initial steps of metastasis, the most lethal aspect of cancer. To study these processes in vitro, the invasion of cells from multicellular breast cancer aggregates embedded in three-dimensional (3D) extracellular matrix culture systems was studied. This work showed that in 3D fibrillar environments composed of collagen I, pore size--not the viscoelastic properties of the matrix--was the biophysical characteristic controlling breast cancer cell invasion efficiency. Furthermore, it was shown that fibrillar matrix architecture is a crucial factor that allows for efficient 3D invasion. In a 3D non-fibrillar environment composed of basement membrane extract (BME), invasion efficiency was greatly diminished, the mesenchymal individual mode of 3D invasion was abolished, and establishment of cell polarity and protrusions was compromised. These effects were seen even though the BME matrix has invasion permissive viscoelasticity and suitable adhesion ligands. The altered and limited invasive behavior observed in BME was rescued through introduction of fibrillar collagen into the non-fibrillar matrix. The biophysical cues of fibrillar collagen facilitated efficient invasion of sterically disadvantageous environments through assisting cell polarization and formation of stable cell protrusions. Finally, we suggest the composite matrices employed in this study consisting of fibrillar collagen I and BME in either a liquid-like or gelled state are suitable for a wide range of 3D cell studies, as these matrices combine fibrillar features that require cells to deploy integrin-dependent mechanotransduction machinery and a tunable non-fibrillar component that may require cells to adopt alternative migratory modes. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

    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. © 2015 Wiley Periodicals, Inc.

  2. Front instabilities and invasiveness of simulated 3D avascular tumors.

    Directory of Open Access Journals (Sweden)

    Nikodem J Poplawski

    2010-05-01

    Full Text Available We use the Glazier-Graner-Hogeweg model to simulate three-dimensional (3D, single-phenotype, avascular tumors growing in an homogeneous tissue matrix (TM supplying a single limiting nutrient. We study the effects of two parameters on tumor morphology: a diffusion-limitation parameter defined as the ratio of the tumor-substrate consumption rate to the substrate-transport rate, and the tumor-TM surface tension. This initial model omits necrosis and oxidative/hypoxic metabolism effects, which can further influence tumor morphology, but our simplified model still shows significant parameter dependencies. The diffusion-limitation parameter determines whether the growing solid tumor develops a smooth (noninvasive or fingered (invasive interface, as in our earlier two-dimensional (2D simulations. The sensitivity of 3D tumor morphology to tumor-TM surface tension increases with the size of the diffusion-limitation parameter, as in 2D. The 3D results are unexpectedly close to those in 2D. Our results therefore may justify using simpler 2D simulations of tumor growth, instead of more realistic but more computationally expensive 3D simulations. While geometrical artifacts mean that 2D sections of connected 3D tumors may be disconnected, the morphologies of 3D simulated tumors nevertheless correlate with the morphologies of their 2D sections, especially for low-surface-tension tumors, allowing the use of 2D sections to partially reconstruct medically-important 3D-tumor structures.

  3. Clonal expansion and linear genome evolution through breast cancer progression from pre-invasive stages to asynchronous metastasis

    DEFF Research Database (Denmark)

    Krøigård, Anne Bruun; Larsen, Martin Jakob; Lænkholm, Anne Vibeke

    2015-01-01

    Evolution of the breast cancer genome from pre-invasive stages to asynchronous metastasis is complex and mostly unexplored, but highly demanded as it may provide novel markers for and mechanistic insights in cancer progression. The increasing use of personalized therapy of breast cancer...... the different stages of tumor evolution in this patient emphasizes the importance of molecular profiling of metastatic tissue directing molecularly targeted therapy at recurrence....

  4. Treatment Approaches to Recurrent Phyllodes Tumors of the Breast

    Directory of Open Access Journals (Sweden)

    Fazilet Erözgen

    2012-06-01

    Full Text Available Aim: Phyllodes tumors of the breast are a rarely encountered clinical condition. Recurrent cases are even rarer. Treatment protocols vary among breast centers. In our study, we aimed to investigate the prognosis of recurrent breast phyllodes tumors and to present our treatment approach. Methods: Among 31000 patients, who presented to our breast outpatient clinic between March 2005 and December 2011, we retrospectively evaluated three patients with recurrent phyllodes tumors of the breast. Results: The three female patients, aged 24, 28 and 30 years, had been previously operated for phyllodes tumor of the breast. The first tumor localization was the superolateral part of the right breast in all subjects. Recurrences were in the same localizations, but pathologies were more aggressive than the previous reports. In two patients mastectomy and in one breast-conserving surgery were performed. Conclusion: Relapse of phyllodes tumors can result in mastectomy and recurrent phyllodes tumors seem to be more aggressive than the original tumor. (The Me di cal Bul le tin of Ha se ki 2012; 50: 43-7

  5. Neuroendocrine Tumor, Well Differentiated, of the Breast: A Relatively High-Grade Case in the Histological Subtype

    Directory of Open Access Journals (Sweden)

    Shogo Tajima

    2013-01-01

    Full Text Available Primary neuroendocrine carcinoma of the breast is a rare entity, comprising <1% of breast carcinomas. Described here is the case of a 78-year-old woman who developed an invasive tumor in the left breast measuring 2.0 cm x 1.5 cm x 1.2 cm. The tumor was composed of only endocrine elements in the invasive part. It infiltrated in a nested fashion with no tubular formation. Intraductal components were present both inside and outside of the invasive portion. Almost all carcinoma cells consisting of invasive and intraductal parts were positive for synaptophysin and neuron-specific enolase. According to the World Health Organization classification 2012, this tumor was subclassified as neuroendocrine tumor, well-differentiated. Among the subgroup, this tumor was relatively high-grade because it was grade 3 tumor with a few mitotic figures. Vascular and lymphatic permeation and lymph node metastases were noted. In the lymph nodes, the morphology of the tumor was similar to the primary site. No distant metastasis and no relapse was seen for one year after surgery. The prognosis of neuroendocrine carcinomas is thought to be worse than invasive mammary carcinomas, not otherwise specified. Therefore, immunohistochemistry for neuroendocrine markers is important in the routine practice to prevent overlooking neuroendocrine carcinomas.

  6. Pathologic tumor response of invasive lobular carcinoma to neo-adjuvant chemotherapy.

    Science.gov (United States)

    Joh, Jennifer E; Esposito, Nicole N; Kiluk, John V; Laronga, Christine; Khakpour, Nazanin; Soliman, Hatem; Catherine Lee, M

    2012-01-01

    Neo-adjuvant chemotherapy is used for locally advanced breast cancer patients with significant variation in tumor response. Our objective is to determine the clinicopathologic effect of neo-adjuvant chemotherapy on invasive lobular carcinoma. A review of a single-institution data base of women diagnosed with breast cancer identified 30 patients from 1999 to 2009 with operable invasive lobular carcinoma who received neo-adjuvant chemotherapy. Patient demographics and clinicopathologic data were reviewed. Cases were reviewed by a single pathologist (NNE). Residual cancer burden class was determined for each case. Median patient age was 50 years (range 25-79). All tumors were hormone receptor positive and clinical stage II or III carcinomas. Most patients (53.3%) had combination anthracycline- and taxane-based chemotherapy. Therapy-related changes were noted within the tumor bed in 25 (83.3%) patients. Six (30%) of 20 patients with residual axillary disease had therapy-related nodal changes. There were 11 patients with moderate residual disease (class II) and 18 (60%) with extensive (class III); there were no complete pathologic responses (class 0). Only one patient (3.3%) converted from mastectomy to breast-conserving surgery. Four (13.3%) patients developed distant metastases; all had pleomorphic-type, clinical stage III tumors with residual cancer burden III classification and developed distant disease in the 2 years after surgery (range 0-26 months). Median follow-up time was 29.5 months (range 7-132). Patients with locally advanced pleomorphic-type lobular carcinoma appear to develop early post-treatment metastatic disease. Neo-adjuvant chemotherapy did not appear to have significant impact on the surgical treatment of patients with invasive lobular carcinoma. © 2012 Wiley Periodicals, Inc.

  7. Epitrochlear lymph node metastases from invasive ductal breast cancer

    Directory of Open Access Journals (Sweden)

    Kumar Pavan

    2009-01-01

    Full Text Available Metastasis to an epitrochlear lymph node from a primary invasive breast cancer has not been reported earlier. We report a case of epitrochlear lymph node metastasis that presented 10 years after the primary breast malignancy had been treated with radiotherapy, chemotherapy, and hormonal therapy. The patient was successfully treated and continues to remain asymptomatic more than 2 years after she presented with the metastasis.

  8. Re-excision rates of invasive ductal carcinoma with lobular features compared with invasive ductal carcinomas and invasive lobular carcinomas of the breast.

    Science.gov (United States)

    Arps, David P; Jorns, Julie M; Zhao, Lili; Bensenhaver, Jessica; Kleer, Celina G; Pang, Judy C

    2014-12-01

    Invasive ductal carcinoma (IDC) with lobular features (IDC-L) is not recognized as a subtype of breast cancer. We previously showed that IDC-L may be a variant of IDC with clinicopathological characteristics more similar to invasive lobular carcinoma (ILC). We sought to determine the re-excision rates of IDC-L compared with ILC and IDC, and the feasibility of diagnosing IDC-L on core biopsies. Surgical procedure, multiple tumor foci, tumor size, and residual invasive carcinoma on re-excision were recorded for IDC-L (n = 178), IDC (n = 636), and ILC (n = 251). Re-excision rates were calculated by excluding mastectomy as first procedure cases and including only re-excisions for invasive carcinoma. Slides of correlating core biopsies for IDC-L cases initially diagnosed as IDC were re-reviewed. For T2 tumors (2.1-5.0 cm), re-excision rates for IDC-L (76 %) and ILC (88 %) were higher than that for IDC (42 %) (p = 0.003). Multiple tumor foci were more common in IDC-L (31 %) and ILC (26 %) than IDC (7 %) (p < 0.0001), which was a significant factor in higher re-excision rates when compared with a single tumor focus (p < 0.001). Ninety-two of 149 patients (62 %) with IDC-L were diagnosed on core biopsies. Of the 44 patients initially diagnosed as IDC, 30 were re-reviewed, of which 24 (80 %) were re-classified as IDC-L. Similar to ILC, re-excision rates for IDC-L are higher than IDC for larger tumors. Patients may need to be counseled about the higher likelihood of additional procedures to achieve negative margins. This underscores the importance of distinguishing IDC-L from IDC on core biopsies.

  9. Estimation of Breast Tumor Conductivity using Parabolic Phase Fitting

    OpenAIRE

    Katscher, U.; Djamshidi, K.; Voigt, T; Ivancevic, M.; Abe, H.; Newstead, G.; Keupp, J.

    2012-01-01

    According to ex vivo studies, breast tumors exhibit a significantlyaltered electric conductivity. This feature opens the chance to increase the specificity of breast tumor characterization with MRI. Theelectric conductivity can be measured in vivo using “Electric Properties Tomography (EPT). EPT has shown its potential in phantom, volunteer, and initial clinical studies. However, the complex frayed structure of fat and ductile tissue in the breast hampers the straight-forward application of E...

  10. Human cytomegalovirus interleukin-10 enhances matrigel invasion of MDA-MB-231 breast cancer cells.

    Science.gov (United States)

    Valle Oseguera, Cendy A; Spencer, Juliet V

    2017-01-01

    While some risk factors for breast cancer are well-known, the influence of other factors, particularly virus infection, remains unclear. Human cytomegalovirus (HCMV) is widespread in the general population, and both molecular and epidemiological evidence has indicated links between HCMV and breast cancer. The HCMV protein cmvIL-10 is a potent suppressor of immune function that has also been shown to promote proliferation and migration of breast cancer cells. In this study, the impact of cmvIL-10 on tumor cell invasion through a simulated basement membrane was investigated. MDA-MB-231 breast cancer cells exhibited invasion through a matrigel layer that was significantly enhanced in the presence of either purified cmvIL-10 or supernatants from HCMV-infected cells containing secreted cmvIL-10. Transcriptional profiling revealed that cmvIL-10 altered expression of several genes implicated in metastasis. Exposure to cmvIL-10 resulted in higher MMP-3 mRNA levels, greater protein expression, and increased enzymatic activity. Treatment with cmvIL-10 also increased expression of both urokinase plasminogen receptor (uPAR) and plasminogen activator inhibitor-1 (PAI-1), which can stimulate MMP-3 activity and have previously been identified as poor prognostic markers in breast cancer patients. Finally, MDA-MB-231 cells treated with cmvIL-10 showed significant downregulation of metastasis suppressor 1 (MTSS1), a scaffolding protein that regulates cytoskeletal rearrangements and is frequently lost in metastatic tumors. HCMV, and in particular the secreted viral cytokine, cmvIL-10, can induce cellular changes that facilitate cell migration and invasion. These findings indicate that HCMV may be associated with promoting the malignant spread of breast cancer cells and suggest that antiviral treatment may be a useful complement to chemotherapy in some patients.

  11. Relationship between reticuloendothelial systems' FDG uptake level and clinicopathological features in patient with invasive ductal breast cancer.

    Science.gov (United States)

    Şahin, Ertan; Elboğa, Umut

    2017-10-01

    The reticuloendothelial system (RES) is a part of the immune system and plays a major role in the protection of against diseases. We thought that FDG-PET/CT may show the degree of systemic immune response induced with malignancy in the organs with the high RES activity. Our objective is to investigate FDG uptake levels of high RES activity organs (liver, spleen, bone marrow) in invasive ductal breast cancer and to evaluate the association with the clinicopathological features. In the present study, 193 patients with invasive ductal breast cancer who performed FDG-PET/CT were categorized according to the clinicopathological features including age, tumor size, axillary nodal status, histological grade, the presence of lymphavascular invasion, receptor status, Ki-67 proliferation index and biological subgroup. Also, a control group of 100 subjects were identified for comparison with breast cancer patients. We analyzed the relation of FDG uptake levels in high RES activity organs and clinicopathological features in patients. There was a statistically significant difference of SUVmax of the liver, spleen, and bone marrow between cancer and control groups (P features in patient with invasive ductal breast cancer. FDG uptake level in high RES activity organs is associated with the presence of tumor, and also directly relating clinicopathological features for patients with invasive ductal breast cancer.

  12. [Differential diagnosis of invasive ductal carcinoma versus invasive lobular carcinoma of breast].

    Science.gov (United States)

    Yin, Hong-Fang; Li, Ting; Zhang, Hong; Zhang, Shuang

    2009-10-01

    To study the diagnostic usefulness of immunohistochemical markers in distinguishing between invasive ductal carcinoma and invasive lobular carcinoma of breast. Twenty-four cases of grade I invasive ductal carcinoma, 12 cases of classic invasive lobular carcinoma and 14 cases of invasive carcinoma with mixed ductal and lobular features were retrieved from the archival files of Peking University First Hospital during the period from January, 1998 to December, 2001. Immunohistochemical study for E-cadherin, p120 catenin, epithelia membrane protein 1 (EMP1) and DVL1 was performed. The positivity rates for E-cadherin in grade I invasive ductal carcinoma and classic invasive lobular carcinoma were 83.3% (20/24) and 0, respectively (P invasive ductal carcinoma (membranous staining) and classic invasive lobular carcinoma (cytoplasmic staining). The positivity rates for EMP1 and DVL1 in gradeI invasive ductal carcinoma were 95.8% (23/24) and 54.2% (13/24), respectively; while those in classic invasive lobular carcinoma were 12 and 5 cases, respectively. E-cadherin and p120 catenin are useful immunomarkers for distinguishing between invasive ductal carcinoma and invasive lobular carcinoma. On the other hand, EMP1 and DVL1 are of limited value in this respect.

  13. Comparison of invasive micropapillary and triple negative invasive ductal carcinoma of the breast.

    Science.gov (United States)

    Chen, Hong-liang; Ding, Ang

    2015-12-01

    Invasive micropapillary carcinoma (IMPC) of the breast and triple negative breast cancer (TNBC) are both aggressive subtypes, but little information is available on their comparison. Retrospective analysis of 95 IMPC and 200 TNBC-IDC (invasive ductal carcinoma) was conducted to compare the clinicopathologic characteristics and survivals. For IMPC, pN was the independent prognostic factor of local-regional recurrence free survival (LRRFS) (P = 0.045) and metastasis free survival (MFS) (P = 0.048), but not of overall survival (OS) (P = 0.165). For TNBC, pT and lymphovascular invasion (LVI) were both independent prognostic factors of MFS (pT: P = 0.006, LVI: P = 0.010) and OS (pT: P = 0.006, LVI: P = 0.001), but not for LRRFS (pT: P = 0.060, LVI: P = 0.503). IMPC exhibited more aggressive features than TNBC, including larger tumor size, a greater proportion of nodal involvement, and an increased incidence of LVI. After a median follow-up duration of 61 months, 5y-LRRFS rate was lower in IMPC than in TNBC, in entire cohort (71.4 ± 4.8% vs. 89.8 ± 2.2%, P < 0.001) and in node positive cases (64.2 ± 5.9% vs. 81.7 ± 4.4%, P = 0.048). A tendency of lower 5y-MFS rate was observed in TNBC compared with in IMPC, in node positive cases (63.8 ± 5.5% vs. 74.8 ± 5.5%, P = 0.053) and in node negative cases (80.1 ± 3.6% vs. 96.2 ± 3.8%, P = 0.052), but it did not reach significance. 5y-OS was similar between IMPC and TNBC (81.9 ± 4.7% vs. 79.8 ± 3.1%, P = 0.475). IMPC is featured with high rate of lymph node involvement which is strongly associated with high rate of LRR. TNBC is featured with high rate of early distant metastasis without increase of nodal metastases. The survival is still relatively poor even in node negative cases. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. RORα, a Potential Tumor Suppressor and Therapeutic Target of Breast Cancer

    Directory of Open Access Journals (Sweden)

    Jun Du

    2012-11-01

    Full Text Available The function of the nuclear receptor (NR in breast cancer progression has been investigated for decades. The majority of the nuclear receptors have well characterized natural ligands, but a few of them are orphan receptors for which no ligand has been identified. RORα, one member of the retinoid orphan nuclear receptor (ROR subfamily of orphan receptors, regulates various cellular and pathological activities. RORα is commonly down-regulated and/or hypoactivated in breast cancer compared to normal mammary tissue. Expression of RORα suppresses malignant phenotypes in breast cancer cells, in vitro and in vivo. Activity of RORα can be categorized into the canonical and non-canonical nuclear receptor pathways, which in turn regulate various breast cancer cellular function, including cell proliferation, apoptosis and invasion. This information suggests that RORα is a potent tumor suppressor and a potential therapeutic target for breast cancer.

  15. Male Malignant Phyllodes Breast Tumor After Prophylactic Breast Radiotherapy and Bicalutamide Treatment: A Case Report.

    Science.gov (United States)

    Karihtala, Peeter; Rissanen, Tarja; Tuominen, Hannu

    2016-07-01

    Phyllodes tumor in male breast is an exceptionally rare neoplasm with only few published case reports. Herein, we present a case of malignant phyllodes tumor in male breast nine years after prophylactic breast 10 Gy radiotherapy and after nine year bicalutamide treatment. The imaging findings of the tumor and pathological correlation are also presented. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  16. Nerve Fibers in Breast Cancer Tissues Indicate Aggressive Tumor Progression

    OpenAIRE

    Huang, Di; Su, Shicheng; Cui, Xiuying; Shen, Ximing; Zeng, Yunjie; Wu, Wei; Chen, Jianing; Chen, Fei; He, Chonghua; Liu, Jiang; Huang, Wei; Liu, Qiang; Su, Fengxi; Song, Erwei; Ouyang, Nengtai

    2014-01-01

    Abstract Emerging evidence has indicated nerve fibers as a marker in the progression of various types of cancers, such as pancreatic cancer and prostate cancer. However, whether nerve fibers are associated with breast cancer progression remains unclear. In this study, we evaluated the presence of nerve fibers in 352 breast cancer specimens and 83 benign breast tissue specimens including 43 cases of cystic fibrosis and 40 cases of fibroadenoma from 2 independent breast tumor center using immun...

  17. Tumor evolution in space: the effects of competition colonization tradeoffs on tumor invasion dynamics

    Directory of Open Access Journals (Sweden)

    Paul A Orlando

    2013-03-01

    Full Text Available We apply competition colonization tradeoff models to tumor growth and invasion dynamics to explore the hypothesis that varying selection forces will result in predictable phenotypic differences in cells at the tumor invasive front compared to those in the core. Spatially, ecologically, and evolutionarily explicit partial differential equation models of tumor growth confirm that spatial invasion produces selection pressure for motile phenotypes. The effects of the invasive phenotype on normal adjacent tissue determine the patterns of growth and phenotype distribution. If tumor cells do not destroy their environment, colonizer and competitive phenotypes coexist with the former localized at the invasion front and the latter, to the tumor interior. If tumors cells do destroy their environment, then cell motility is strongly selected resulting in accelerated invasion speed with time. Our results suggest that the widely observed genetic heterogeneity within cancers may not be the stochastic effect of random mutations. Rather, it may be the consequence of predictable variations in environmental selection forces and corresponding phenotypic adaptations.

  18. Invasive ductal breast cancer metastatic to the sigmoid colon

    Directory of Open Access Journals (Sweden)

    Zhou Xiao-cong

    2012-11-01

    Full Text Available Abstract The most common sites of breast cancer metastasis are the bone, lung, liver and brain. However, colonic metastases from breast cancer are very rare in the clinic. We describe an unusual case of sigmoid colonic metastasis from invasive ductal breast cancer. With this report, we should increase the clinical awareness that any patient with a colorectal lesion and a history of malignancy should be considered to have a metastasis until proven otherwise. Early diagnosis is very important, which enables prompt initiation of systemic treatment, such as chemotherapy, endocrine therapy or both, thus avoiding unnecessary radical surgical resection and improving the prognosis.

  19. Clonal expansion and linear genome evolution through breast cancer progression from pre-invasive stages to asynchronous metastasis

    DEFF Research Database (Denmark)

    Krøigård, Anne Bruun; Larsen, Martin Jakob; Lænkholm, Anne-Vibeke

    2015-01-01

    Evolution of the breast cancer genome from pre-invasive stages to asynchronous metastasis is complex and mostly unexplored, but highly demanded as it may provide novel markers for and mechanistic insights in cancer progression. The increasing use of personalized therapy of breast cancer...... necessitates knowledge of the degree of genomic concordance between different steps of malignant progression as primary tumors often are used as surrogates of systemic disease. Based on exome sequencing we performed copy number profiling and point mutation detection on successive steps of breast cancer...... progression from one breast cancer patient, including two different regions of Ductal Carcinoma In Situ (DCIS), primary tumor and an asynchronous metastasis. We identify a remarkable landscape of somatic mutations, retained throughout breast cancer progression and with new mutational events emerging at each...

  20. Shear-wave elastography of invasive breast cancer: correlation between quantitative mean elasticity value and immunohistochemical profile.

    Science.gov (United States)

    Youk, Ji Hyun; Gweon, Hye Mi; Son, Eun Ju; Kim, Jeong-Ah; Jeong, Joon

    2013-02-01

    To compare the mean elasticity value, as measured by shear-wave elastography (SWE), with immunohistochemical profile of invasive breast cancer. This was an institutional review board-approved retrospective study, with a waiver of informed consent. A total of 166 invasive breast cancers in 152 women undergoing preoperative SWE and surgery were included. Quantitative mean elasticity values in kPa were measured for each lesion by using SWE. Medical records were reviewed to determine palpability, invasive size, lymphovascular invasion, histologic grade, and axillary lymph node status. Based on the immunohistochemical profiles, tumor subtypes were categorized as triple-negative (TN), luminal A and B, or human epidermal growth factor receptor 2-enriched cancer. The mean elasticity value was correlated with clinicopathological features using univariate regression models and multivariate linear regression analysis. Palpability (P elasticity value. For the immunohistochemical profiles and tumor subtypes, the estrogen receptor (P = 0.015), progesterone receptor (P = 0.002), Ki-67 (P = 0.009), and the TN (P = 0.009) tumor subtype were correlated with the mean elasticity value. Multivariate logistic regression analysis showed that the following variables were significantly associated with the mean elasticity value: palpable abnormality, histologic grade, and lymphovascular invasion. No immunohistochemical profile of the cancers was independently correlated with the mean elasticity value. For invasive breast cancers, clinicopathological features of poor prognosis showed higher mean elasticity values than those of good prognosis. However, the immunohistochemical profile showed no independent association with the mean elasticity value.

  1. A RAB5/RAB4 recycling circuitry induces a proteolytic invasive program and promotes tumor dissemination

    Science.gov (United States)

    Frittoli, Emanuela; Palamidessi, Andrea; Marighetti, Paola; Confalonieri, Stefano; Bianchi, Fabrizio; Malinverno, Chiara; Mazzarol, Giovanni; Viale, Giuseppe; Martin-Padura, Ines; Garré, Massimilliano; Parazzoli, Dario; Mattei, Valentina; Cortellino, Salvatore; Bertalot, Giovanni

    2014-01-01

    The mechanisms by which tumor cells metastasize and the role of endocytic proteins in this process are not well understood. We report that overexpression of the GTPase RAB5A, a master regulator of endocytosis, is predictive of aggressive behavior and metastatic ability in human breast cancers. RAB5A is necessary and sufficient to promote local invasion and distant dissemination of various mammary and nonmammary tumor cell lines, and this prometastatic behavior is associated with increased intratumoral cell motility. Specifically, RAB5A is necessary for the formation of invadosomes, membrane protrusions specialized in extracellular matrix (ECM) degradation. RAB5A promotes RAB4- and RABENOSYN-5–dependent endo/exocytic cycles (EECs) of critical cargos (membrane-type 1 matrix metalloprotease [MT1-MMP] and β3 integrin) required for invadosome formation in response to motogenic stimuli. This trafficking circuitry is necessary for spatially localized hepatocyte growth factor (HGF)/MET signaling that drives invasive, proteolysis-dependent chemotaxis in vitro and for conversion of ductal carcinoma in situ to invasive ductal carcinoma in vivo. Thus, RAB5A/RAB4 EECs promote tumor dissemination by controlling a proteolytic, mesenchymal invasive program. PMID:25049275

  2. Contrast-enhanced dedicated breast CT detection of invasive breast cancer preceding mammographic diagnosis

    OpenAIRE

    Prionas, Nicolas D.; Aminololama-Shakeri, Shadi; Yang, Kai; Martinez, Steve R.; Lindfors, Karen K.; Boone, John M.

    2015-01-01

    Dedicated breast computed tomography (bCT) generates high-resolution, three-dimensional images of the pendent uncompressed breast. Intravenous iodinated contrast during bCT provides additional physiologic information. In this case, a 10.0-mm invasive ductal carcinoma was visualized using contrast-enhanced breast CT one year before mammographic detection. Mammography four months before bCT was negative. The bCT contrast enhancement pattern closely matched the dynamic contrast-enhanced MRI obta...

  3. Radiofrequency Ablation: A Minimally Invasive Approach in Kidney Tumor Management

    Energy Technology Data Exchange (ETDEWEB)

    Salagierski, Maciej, E-mail: maciej.salagierski@umed.lodz.pl [I Urology Department, Medical University of Lodz (Poland); Salagierski, Marek S. [II Urology Department, Medical University of Lodz (Poland)

    2010-11-17

    The management and diagnosis of renal tumors have changed significantly over the last decade. Due to advances in imaging techniques, more than 50% of kidney tumors are discovered incidentally and many of them represent an early stage lesion. This has stimulated the development of nephron-sparing surgery and of the minimally invasive treatment options including ablative techniques, i.e., radiofrequency ablation (RFA) and cryoablation. The objective of the minimally invasive approach is to preserve the renal function and to lower the perioperative morbidity. RFA involves inducing the coagulative necrosis of tumor tissue. Being probably one of the least invasive procedures in kidney tumor management, RFA may be performed percutaneously under ultrasound (US), computed tomography (CT) or magnetic resonance (MR) guidance. Most of the studies show that the RFA procedure is efficient, safe and has a low complication rate. Due to the still limited data on the oncological outcome of RFA, the indication for this intervention remains limited to selected patients with small organ-confined renal tumors and contraindication to surgery or who have a solitary kidney. The aim of our study is to review the literature on RFA of kidney tumors.

  4. The aryl hydrocarbon receptor ligand omeprazole inhibits breast cancer cell invasion and metastasis.

    Science.gov (United States)

    Jin, Un-Ho; Lee, Syng-Ook; Pfent, Catherine; Safe, Stephen

    2014-07-09

    Patients with ER-negative breast tumors are among the most difficult to treat and exhibit low survival rates due, in part, to metastasis from the breast to various distal sites. Aryl hydrocarbon receptor (AHR) ligands show promise as antimetastatic drugs for estrogen receptor (ER)-negative breast cancer. Triple negative MDA-MB-231 breast cancer cells were treated with eight AHR-active pharmaceuticals including 4-hydroxtamoxifen, flutamide leflunomide, mexiletine, nimodipine, omeprazole, sulindac and tranilast, and the effects of these compounds on cell proliferation (MTT assay) and cell migration (Boyden chamber assay) were examined. The role of the AHR in mediating inhibition of MDA-MB-231 cell invasion was investigated by RNA interference (RNAi) and knockdown of AHR or cotreatment with AHR agonists. Lung metastasis of MDA-MB-231 cells was evaluated in mice administered cells by tail vein injection and prometastatic gene expression was examined by immunohistochemistry. We showed that only the proton pump inhibitor omeprazole decreased MDA-MB-231 breast cancer cell invasion in vitro. Omeprazole also significantly decreased MDA-MB-231 cancer cell metastasis to the lung in a mouse model (tail vein injection), and in vitro studies showed that omeprazole decreased expression of at least two prometastatic genes, namely matrix metalloproteinase-9 (MMP-9) and C-X-C chemokine receptor 4 (CXCR4). Results of RNA interference studies confirmed that omeprazole-mediated downregulation of CXCR4 (but not MMP-9) was AHR-dependent. Chromatin immunoprecipitation assays demonstrated that omeprazole recruited the AHR to regions in the CXCR4 promoter that contain dioxin response elements (DREs) and this was accompanied by the loss of pol II on the promoter and decreased expression of CXCR4. AHR-active pharmaceuticals such as omeprazole that decrease breast cancer cell invasion and metastasis may have important clinical applications for late stage breast cancer chemotherapy.

  5. Effects of Mechanical Properties on Tumor Invasion: Insights from a Cellular Model

    KAUST Repository

    Li, YZ

    2014-08-01

    Understanding the regulating mechanism of tumor invasion is of crucial importance for both fundamental cancer research and clinical applications. Previous in vivo experiments have shown that invasive cancer cells dissociate from the primary tumor and invade into the stroma, forming an irregular invasive morphology. Although cell movements involved in tumor invasion are ultimately driven by mechanical forces of cell-cell interactions and tumor-host interactions, how these mechanical properties affect tumor invasion is still poorly understood. In this study, we use a recently developed two-dimensional cellular model to study the effects of mechanical properties on tumor invasion. We study the effects of cell-cell adhesions as well as the degree of degradation and stiffness of extracellular matrix (ECM). Our simulation results show that cell-cell adhesion relationship must be satisfied for tumor invasion. Increased adhesion to ECM and decreased adhesion among tumor cells result in invasive tumor behaviors. When this invasive behavior occurs, ECM plays an important role for both tumor morphology and the shape of invasive cancer cells. Increased stiffness and stronger degree of degradation of ECM promote tumor invasion, generating more aggressive tumor invasive morphologies. It can also generate irregular shape of invasive cancer cells, protruding towards ECM. The capability of our model suggests it a useful tool to study tumor invasion and might be used to propose optimal treatment in clinical applications.

  6. 17β-Estradiol treatment inhibits breast cell proliferation, migration and invasion by decreasing MALAT-1 RNA level

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Ziyi [Key Laboratory of Bioresources and Ecoenvironment (Ministry of Education), College of Life Sciences, Sichuan University, Chengdu 610041 (China); Chen, Changjin [Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu 610041 (China); Liu, Yu [Key Laboratory of Bioresources and Ecoenvironment (Ministry of Education), College of Life Sciences, Sichuan University, Chengdu 610041 (China); Wu, Chuanfang, E-mail: 879413966@qq.com [Key Laboratory of Bioresources and Ecoenvironment (Ministry of Education), College of Life Sciences, Sichuan University, Chengdu 610041 (China)

    2014-03-07

    Highlights: • E2 affects not only estrogen-receptor α positive breast cells but also negative ones. • 100 nM E2 treatment affects breast cells proliferation, migration. • 100 nM E2 treatment functions in an estrogen-receptor α-independent way. • E2 treatment decreases MALAT-1 RNA level by post-transcriptional regulation. - Abstract: Breast cancer cells, which express estrogen receptor α (ERα), respond to estrogen in a concentration dependent fashion, resulting in proliferation or apoptosis. But breast cancer cells without ERα show no effect on low concentration of estrogen treatment. Proliferation, migration and invasion of MCF10a, MCF7 and MB231 cells treated with low (1 nM) or high (100 nM) dose of 17β-Estradiol (E2) was performed. We identified the effects of E2 on these breast cell lines, and looked for the difference in the presence and absence of ERα. Specifically, we looked for the changes of long non-coding RNA metastasis associated lung adenocarcinoma transcript 1 (MALAT-1), which is found extensively and highly expressed in several kinds of tumor cells, including breast carcinoma. It was observed that proliferation, migration and invasion of breast cells were greatly affected by high concentration E2 treatment and were not affected by low concentration E2 treatment in an ERα independent way. We found that the high concentration E2 treatment largely decreased MALAT-1 RNA level. Interestingly, MALAT-1 decreasing by knocking down showed similar effects on proliferation, migration and invasion. E2 treatment affects breast tumor or non-tumor cells proliferation, migration and invasion in an ERα -independent, but a dose-dependent way by decreasing the MALAT-1 RNA level.

  7. MR-tomographic appearance of invasive lobular carcinoma of the breast; Case study. Das lobulaere Mammakarzinom in der Kernspintomographie; Ein Fallbeispiel

    Energy Technology Data Exchange (ETDEWEB)

    Wilhelm, K. (Inst. fuer Klinische Strahlenkunde, Universitaetsklinik Mainz (Germany)); Grebe, P. (Inst. fuer Klinische Strahlenkunde, Universitaetsklinik Mainz (Germany)); Teifke, A. (Inst. fuer Klinische Strahlenkunde, Universitaetsklinik Mainz (Germany)); Halbsguth, A. (Radiologische Gemeinschaftspraxis, Frankfurt am Main (Germany)); Mitze, M. (Klinik und Poliklinik fuer Geburtshilfe und Frauenkrankheiten, Universitaetsklinik Mainz (Germany)); Thelen, M. (Inst. fuer Klinische Strahlenkunde, Universitaetsklinik Mainz (Germany))

    1992-11-01

    The invasive lobular carcinoma of the breast, the incidence of which is 10-15%, occupies a special position in respect of histological differentiation and biological behaviour. No MR signal enhancement was seen after contrast medium application in the tumoral tissue in the case described here, namely, an invasive lobular carcinoma of the breast of 2 cm size. Hence, it is not always possible to exclude with absolute certainty the presence especially of an invasive lobular carcinoma of the breast in the absence of contrast medium uptake. (orig.)

  8. A systematic review to establish the frequency of cyclooxygenase-2 expression in normal breast epithelium, ductal carcinoma in situ, microinvasive carcinoma of the breast and invasive breast cancer

    OpenAIRE

    Glover, J A; Hughes, C M; Cantwell, M M; Murray, L J

    2011-01-01

    Background: Epidemiological studies have suggested a protective effect of cyclooxygenase (COX)-inhibiting non-steroidal anti-inflammatory drugs in breast cancer risk and disease progression. We performed a systematic review to evaluate the frequency of COX-2 expression in normal breast epithelium, ductal carcinoma in situ of breast (DCIS), DCIS-adjoining invasive breast cancer, microinvasive carcinoma of the breast (MICB) and invasive breast cancer. Methods: Literature searches were carried o...

  9. The assessment of angiogenesis and fibroblastic stromagenesis in hyperplastic and pre-invasive breast lesions

    Directory of Open Access Journals (Sweden)

    Louvrou Niki

    2008-04-01

    Full Text Available Abstract Background To investigate the changes of the neoplastic microenvironment during the different morphological alterations of hyperplastic and pre-invasive breast lesions. Methods 78 in situ ductal carcinomas of all degrees of differentiation, 22 atypical ductal hyperplasias, 25 in situ lobular carcinomas, 18 atypical lobular hyperplasias, 32 ductal epithelial hyperplasias of usual type and 8 flat atypias were immunohistochemically investigated for the expression of vascular endothelial growth factor (VEGF, smooth muscle actin (SMA and CD34, while microvessel density (MVD was counted using the anti-CD31 antibody. Results VEGF expression was strongly correlated with MVD in all hyperplastic and pre-invasive breast lesions (p Conclusion Angiogenesis is observed before any significant fibroblastic stromagenesis in pre-invasive breast lesions. A composite phenotype characterized by VEGF positive epithelial cells and SMA positive/CD34 negative stromal cells, is identified mostly in intermediate and high grade DCIS. These findings might imply for new therapeutic strategies using both anti-angiogenic factors and factors selectively targeting tumor stroma in order to prevent the progression of DCIS to invasive carcinoma.

  10. Clinical outcomes using accelerated partial breast irradiation in patients with invasive lobular carcinoma.

    Science.gov (United States)

    Shah, Chirag; Wilkinson, J Ben; Shaitelman, Simona; Grills, Inga; Wallace, Michelle; Mitchell, Christina; Vicini, Frank

    2011-11-15

    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). 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. 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 invasive lobular versus invasive ductal histology. Copyright © 2011 Elsevier Inc. All rights reserved.

  11. Giant phyllodes tumor of the breast: a clinical observation

    Directory of Open Access Journals (Sweden)

    A. A. Volchenko

    2012-01-01

    Full Text Available The paper describes a case of giant phyllodes tumor of the breast. Phyllodes tumor is a rare type of fibroepithelial tumor composed of epithelial and connective tissue with the predominant development of a connective tissue component. Surgery is the only radical treatment.

  12. The TGF-β/Smad pathway induces breast cancer cell invasion through the up-regulation of matrix metalloproteinase 2 and 9 in a spheroid invasion model system.

    Science.gov (United States)

    Wiercinska, Eliza; Naber, Hildegonda P H; Pardali, Evangelia; van der Pluijm, Gabri; van Dam, Hans; ten Dijke, Peter

    2011-08-01

    Transforming growth factor-β (TGF-β) has opposing roles in breast cancer progression by acting as a tumor suppressor in the initial phase, but stimulating invasion and metastasis at later stages. In contrast to the mechanisms by which TGF-β induces growth arrest, the pathways that mediate tumor invasion are not well understood. Here, we describe a TGF-β-dependent invasion assay system consisting of spheroids of MCF10A1 normal breast epithelial cells (M1) and RAS-transformed (pre-)malignant derivatives (M2 and M4) embedded in collagen gels. Both basal and TGF-β-induced invasion of these cell lines was found to correlate with their tumorigenic potential; M4 showing the most aggressive behavior and M1 showing the least. Basal invasion was strongly inhibited by the TGF-β receptor kinase inhibitor SB-431542, indicating the involvement of autocrine TGF-β or TGF-β-like activity. TGF-β-induced invasion in premalignant M2 and highly malignant M4 cells was also inhibited upon specific knockdown of Smad3 or Smad4. Interestingly, both a broad spectrum matrix metalloproteinase (MMP) inhibitor and a selective MMP2 and MMP9 inhibitor mitigated TGF-β-induced invasion of M4 cells, while leaving basal invasion intact. In line with this, TGF-β was found to strongly induce MMP2 and MMP9 expression in a Smad3- and Smad4-dependent manner. This collagen-embedded spheroid system therefore offers a valuable screening model for TGF-β/Smad- and MMP2- and MMP9-dependent breast cancer invasion.

  13. Emergent Behavior from A Cellular Automaton Model for Invasive Tumor Growth in Heterogeneous Microenvironments

    CERN Document Server

    Jiao, Yang

    2011-01-01

    Understanding tumor invasion and metastasis is of crucial importance for both fundamental cancer research and clinical practice. In vitro experiments have established that the invasive growth of malignant tumors is characterized by the dendritic invasive branches composed of chains of tumor cells emanating from the primary tumor mass. The preponderance of previous tumor simulations focused on non-invasive (or proliferative) growth. The formation of the invasive cell chains and their interactions with the primary tumor mass and host microenvironment are not well understood. Here, we present a novel cellular automaton (CA) model that enables one to efficiently simulate invasive tumor growth in a heterogeneous host microenvironment. By taking into account a variety of microscopic-scale tumor-host interactions, including the short-range mechanical interactions between tumor cells and tumor stroma, degradation of extracellular matrix by the invasive cells and oxygen/nutrient gradient driven cell motions, our CA mo...

  14. Intravital multiphoton imaging reveals multicellular streaming as a crucial component of in vivo cell migration in human breast tumors

    Science.gov (United States)

    Patsialou, Antonia; Bravo-Cordero, Jose Javier; Wang, Yarong; Entenberg, David; Liu, Huiping; Clarke, Michael; Condeelis, John S.

    2014-01-01

    Metastasis is the main cause of death in breast cancer patients. Cell migration is an essential component of almost every step of the metastatic cascade, especially the early step of invasion inside the primary tumor. In this report, we have used intravital multiphoton microscopy to visualize the different migration patterns of human breast tumor cells in live primary tumors. We used xenograft tumors of MDA-MB-231 cells as well as a low passage xenograft tumor from orthotopically injected patient-derived breast tumor cells. Direct visualization of human tumor cells in vivo shows two patterns of high-speed migration inside primary tumors: a. single cells and b. multicellular streams (i.e., cells following each other in a single file but without cohesive cell junctions). Critically, we found that only streaming and not random migration of single cells was significantly correlated with proximity to vessels, with intravasation and with numbers of elevated circulating tumor cells in the bloodstream. Finally, although the two human tumors were derived from diverse genetic backgrounds, we found that their migratory tumor cells exhibited coordinated gene expression changes that led to the same end-phenotype of enhanced migration involving activating actin polymerization and myosin contraction. Our data are the first direct visualization and assessment of in vivo migration within a live patient-derived breast xenograft tumor. PMID:25013744

  15. Malignant Mesothelioma Mimicking Invasive Mammary Carcinoma in a Male Breast

    Directory of Open Access Journals (Sweden)

    Mohamed Mokhtar Desouki

    2015-01-01

    Full Text Available Malignant mesothelioma is an uncommon tumor with strong association with asbestos exposure. Few cases of malignant pleural mesothelioma metastatic to the female breast have been reported. Herein, we presented, for the first time, a case of locally infiltrating malignant pleural mesothelioma forming a mass in the breast of a male as the first pathologically confirmed manifestation of the disease. Breast ultrasound revealed an irregular mass in the right breast which involves the pectoralis muscle. Breast core biopsy revealed a proliferation of neoplastic epithelioid cells mimicking an infiltrating pleomorphic lobular carcinoma. IHC studies showed the cells to be positive for calretinin, CK5/6, WT1, and CK7. The cells were negative for MOC-31, BerEp4, ER, and PR. A final diagnosis of malignant mesothelioma, epithelioid type, was rendered. This case demonstrates the importance of considering a broad differential diagnosis in the setting of atypical presentation with application of a panel of IHC markers.

  16. Invasive lobular carcinoma of the breast: morphology, biomarkers and 'omics.

    Science.gov (United States)

    McCart Reed, Amy E; Kutasovic, Jamie R; Lakhani, Sunil R; Simpson, Peter T

    2015-01-30

    Invasive lobular carcinoma of the breast is the most common 'special' morphological subtype of breast cancer, comprising up to 15% of all cases. Tumours are generally of a good prognostic phenotype, being low histological grade and low mitotic index, hormone receptor positive and HER2, p53 and basal marker negative, and with a generally good response to endocrine therapy. Despite this, clinicians face countless challenges in the diagnosis and long-term management of patients, as they encounter a tumour that can be difficult to detect through screening, elicits a very invasive nature, a propensity for widespread metastatic colonisation and, consequently, in some studies a worse long-term poor outcome compared with invasive carcinoma of no special type. Here we review the morphological and molecular features that underpin the disparate biological and clinical characteristics of this fascinating tumour type.

  17. SKI-606 (bosutinib), a novel Src kinase inhibitor, suppresses migration and invasion of human breast cancer cells

    Science.gov (United States)

    Vultur, Adina; Buettner, Ralf; Kowolik, Claudia; Liang, Wei; Smith, David; Boschelli, Frank; Jove, Richard

    2009-01-01

    Src family kinase (SFK) activity is elevated in many human tumors, including breast cancer, and is often associated with aggressive disease. We examined the effects of SKI-606 (bosutinib), a selective SFK inhibitor, on human cancer cells derived from breast cancer patients in order to assess its potential for breast cancer treatment. Our results show that SKI-606 caused a decrease in cell motility and invasion of breast cancer cell lines with an IC50 of ~250 nM, which was also the IC50 for inhibition of c-Src kinase activity in intact tumor cells. These changes were accompanied by an increase in cell-to-cell adhesion and membrane localization of beta-catenin. By contrast, cell proliferation and survival were unaffected by SKI-606 at concentrations sufficient to block cell migration and invasion. Analysis of downstream effectors of Src revealed that SKI-606 inhibits the phosphorylation of focal adhesion kinase (FAK), proline-rich tyrosine kinase 2 (Pyk2) and Crk-associated substrate (p130Cas) with an IC50 similar to inhibition of c-Src kinase. Our findings indicate that SKI-606 inhibits signaling pathways involved in controlling tumor cell motility and invasion, suggesting that SKI-606 is a promising therapeutic for breast cancer. PMID:18483306

  18. Dense and nondense mammographic area and risk of breast cancer by age and tumor characteristics.

    Science.gov (United States)

    Bertrand, Kimberly A; Scott, Christopher G; Tamimi, Rulla M; Jensen, Matthew R; Pankratz, V Shane; Norman, Aaron D; Visscher, Daniel W; Couch, Fergus J; Shepherd, John; Chen, Yunn-Yi; Fan, Bo; Wu, Fang-Fang; Ma, Lin; Beck, Andrew H; Cummings, Steven R; Kerlikowske, Karla; Vachon, Celine M

    2015-05-01

    Mammographic density (MD) is a strong breast cancer risk factor. We previously reported associations of percent mammographic density (PMD) with larger and node-positive tumors across all ages, and estrogen receptor (ER)-negative status among women ages breast cancer subtypes. Data were pooled from six studies including 4,095 breast cancers and 8,558 controls. DA and NDA were assessed from digitized film-screen mammograms and standardized across studies. Breast cancer odds by density phenotypes and age according to histopathologic characteristics and receptor status were calculated using polytomous logistic regression. DA was associated with increased breast cancer risk [OR for quartiles: 0.65, 1.00 (Ref), 1.22, 1.55; P(trend) ages and invasive tumor characteristics. There were significant trends in the magnitude of associations of both DA and NDA with breast cancer by increasing tumor size (P(trend) age. DA and NDA are important to consider when developing age- and subtype-specific risk models. ©2015 American Association for Cancer Research.

  19. Noninvasive measurement of the electrical bioimpedance of breast tumors.

    Science.gov (United States)

    Ohmine, Y; Morimoto, T; Kinouchi, Y; Iritani, T; Takeuchi, M; Monden, Y

    2000-01-01

    The purpose of this study was to evaluate the possibility of differential diagnosis of tumors, such as breast cancer, by measuring the mammary electrical bioimpedance via the skin surface noninvasively and by examining the relationship between the tissue structure of the breast and electrical bioimpedance. The mammary electrical bioimpedance was measured in 24 patients with breast cancer. Taking into account the measurement results and the distribution of the mammary glands and fatty tissue, a breast model with tumors was proposed. Based on this model, the distributions of the electric potential and electric field in the tissue were theoretically analyzed by the three-dimensional finite element method. In clinical cases, the Re values of the diseased breast were significantly larger than those of the contralateral healthy breast. In theoretical analysis based on the breast model, the Re value of mammary electrical bioimpedance varied due to the structure of the breast, that is, the ratio of fatty tissue to mammary gland and the presence of mammary tumors. The results of the measurement agreed with the theoretical analyses. These results suggest that differential diagnosis of breast tumors is possible by measuring the mammary electrical bioimpedance using noninvasive electrodes on the skin.

  20. Spatial distribution of mast cells and macrophages around tumor glands in human breast ductal carcinoma.

    Science.gov (United States)

    Tamma, Roberto; Guidolin, Diego; Annese, Tiziana; Tortorella, Cinzia; Ruggieri, Simona; Rega, Serena; Zito, Francesco A; Nico, Beatrice; Ribatti, Domenico

    2017-10-01

    Macrophages and mast cells are usually present in the tumor microenvironment and play an important role as regulators of inflammation, immunological response and angiogenesis in the tumor microenvironment. In this study, we have evaluated macrophage, mast cell, and microvessel density in a selected group of different grade of invasive breast carcinoma tumor specimens. Furthermore, we have investigated the pattern of distribution of CD68-positive macrophages and tryptase-positive mast cells around tumor glands. Results have shown that: A) Macrophages are more numerous in G2 and G3 breast cancer stages respect to controls, the per cent of macrophages in G1 samples was comparable to the controls, and the spatial relationship between macrophages and glands (as indicated by the mean cell-to-gland distance) correlated with CD31-positive vessels. B) Mast cells in G2 and G3 tumor specimens show a significant increase in their number as compared to control samples, and their spatial distribution around the glands did not show any significant difference among groups. Overall, the results of this study confirm the important role of macrophages and mast cells in tumor progression and angiogenesis in human ductal breast cancer, and pointed out the spatial relationship between tumor macrophages and glands, and its correlation with microvascular density. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Cell jamming: Collective invasion of mesenchymal tumor cells imposed by tissue confinement

    NARCIS (Netherlands)

    Haeger, A.; Krause, M.; Wolf, K. van der; Friedl, P.

    2014-01-01

    BACKGROUND: Cancer invasion is a multi-step process which coordinates interactions between tumor cells with mechanotransduction towards the surrounding matrix, resulting in distinct cancer invasion strategies. Defined by context, mesenchymal tumors, including melanoma and fibrosarcoma, develop

  2. Functional characterization of E- and P-cadherin in invasive breast cancer cells

    Directory of Open Access Journals (Sweden)

    Cano Amparo

    2009-03-01

    Full Text Available Abstract Background Alterations in the cadherin-catenin adhesion complexes are involved in tumor initiation, progression and metastasis. However, the functional implication of distinct cadherin types in breast cancer biology is still poorly understood. Methods To compare the functional role of E-cadherin and P-cadherin in invasive breast cancer, we stably transfected these molecules into the MDA-MB-231 cell line, and investigated their effects on motility, invasion and gene expression regulation. Results Expression of either E- and P-cadherin significantly increased cell aggregation and induced a switch from fibroblastic to epithelial morphology. Although expression of these cadherins did not completely reverse the mesenchymal phenotype of MDA-MB-231 cells, both E- and P-cadherin decreased fibroblast-like migration and invasion through extracellular matrix in a similar way. Moreover, microarray gene expression analysis of MDA-MB-231 cells after expression of E- and P-cadherins revealed that these molecules can activate signaling pathways leading to significant changes in gene expression. Although the expression patterns induced by E- and P-cadherin showed more similarities than differences, 40 genes were differentially modified by the expression of either cadherin type. Conclusion E- and P-cadherin have similar functional consequences on the phenotype and invasive behavior of MDA-MB-231 cells. Moreover, we demonstrate for the first time that these cadherins can induce both common and specific gene expression programs on invasive breast cancer cells. Importantly, these identified genes are potential targets for future studies on the functional consequences of altered cadherin expression in human breast cancer.

  3. Liposomes, modified with PTD(HIV-1) peptide, containing epirubicin and celecoxib, to target vasculogenic mimicry channels in invasive breast cancer.

    Science.gov (United States)

    Ju, Rui-Jun; Li, Xue-Tao; Shi, Ji-Feng; Li, Xiu-Ying; Sun, Meng-Ge; Zeng, Fan; Zhou, Jia; Liu, Lei; Zhang, Cheng-Xiang; Zhao, Wei-Yu; Lu, Wan-Liang

    2014-08-01

    Refractoriness of invasive breast cancer is closely related with the vasculogenic mimicry (VM) channels, which exhibit highly drug resistance to conventional chemotherapies. In the present study, the nanostructured targeting epirubicin plus celecoxib liposomes were developed by modifying a human immunodeficiency virus peptide lipid-derivative conjugate (DSPE-PEG2000-PTDHIV-1) for elimination of invasive breast cancer cells along with their VM channels. The studies were undertaken on invasive human breast cancer MDA-MB-435S cells and MDA-MB-435S xenografts in nude mice. The constructed targeting epirubicin plus celecoxib liposomes were approximately 100 nm in size. In vitro results showed that the targeting liposomes exhibited strong transport ability across cell and nuclei membranes of invasive breast cancer, were able to penetrate and destruct the invasive breast cancer spheroids, initiated apoptosis via activating apoptotic enzymes (caspase 8, 3), and destroyed the VM channels via down-regulating the protein indicators (MMP-9, VE-Cad, FAK, EphA2 and HIF-1α) in invasive breast cancer cells. In vivo results demonstrated that the targeting liposomes displayed a prolonged circulation time in blood system, accumulated more in tumor location, were able to eliminate the VM channels and angiogenesis in tumor tissues, and resulted in a robust overall anticancer efficacy in invasive breast cancer MDA-MB-435S xenografts in nude mice. In conclusion, the nanostructured targeting epirubicin plus celecoxib liposomes could eliminate invasive breast cancer along with the VM channels, hence providing a promising strategy for treatment of invasive breast cancer. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Pattern of Ipsilateral Breast Tumor Recurrence After Breast-Conserving Therapy

    NARCIS (Netherlands)

    Jobsen, Jan; van der Palen, Jacobus Adrianus Maria; Riemersma, Sietske; Heijmans, Harald; Ong, Francisca; Struikmans, Henk

    2014-01-01

    The rate of ipsilateral breast tumor recurrence (IBTR) in breast cancer after breast-conserving therapy was analyzed. We demonstrate that after 12 years' follow-up, there is an especially high recurrence rate for women ≤40 years old. For women ≤40 years old, the absence of adjuvant systemic therapy

  5. Estrogen switches pure mucinous breast cancer to invasive lobular carcinoma with mucinous features.

    Science.gov (United States)

    Jambal, Purevsuren; Badtke, Melanie M; Harrell, J Chuck; Borges, Virginia F; Post, Miriam D; Sollender, Grace E; Spillman, Monique A; Horwitz, Kathryn B; Jacobsen, Britta M

    2013-01-01

    Mucinous breast cancer (MBC) is mainly a disease of postmenopausal women. Pure MBC is rare and augurs a good prognosis. In contrast, MBC mixed with other histological subtypes of invasive disease loses the more favorable prognosis. Because of the relative rarity of pure MBC, little is known about its cell and tumor biology and relationship to invasive disease of other subtypes. We have now developed a human breast cancer cell line called BCK4, in which we can control the behavior of MBC. BCK4 cells were derived from a patient whose poorly differentiated primary tumor was treated with chemotherapy, radiation and tamoxifen. Malignant cells from a recurrent pleural effusion were xenografted in mammary glands of a nude mouse. Cells from the solid tumor xenograft were propagated in culture to generate the BCK4 cell line. Multiple marker and chromosome analyses demonstrate that BCK4 cells are human, near diploid and luminal, expressing functional estrogen, androgen, and progesterone receptors. When xenografted back into immunocompromised cycling mice, BCK4 cells grow into small pure MBC. However, if mice are supplemented with continuous estradiol, tumors switch to invasive lobular carcinoma (ILC) with mucinous features (mixed MBC), and growth is markedly accelerated. Tamoxifen prevents the expansion of this more invasive component. The unexpected ability of estrogens to convert pure MBC into mixed MBC with ILC may explain the rarity of the pure disease in premenopausal women. These studies show that MBC can be derived from lobular precursors and that BCK4 cells are new, unique models to study the phenotypic plasticity, hormonal regulation, optimal therapeutic interventions, and metastatic patterns of MBC.

  6. Phyllodes tumor masquerading as a fungating breast mass.

    Science.gov (United States)

    Bruce, Nolan R; Carlson, Jacob T; Barnard, Kayla J; Henry-Tillman, Ronda

    2017-12-01

    Phyllodes tumor of the breast is an uncommonly encountered disease. The tumor presenting as fungating breast mass or 'ruptured' breast is an even more rare presentation of an unusual disease. This report documents the case of a 60-year-old female with delayed presentation of a large exophytic mass of the left breast. Biopsy of this lesion was non-diagnostic, so excision via left total mastectomy was performed. The final pathology was consistent with malignant phyllodes tumor. This report highlights the features of a rare breast cancer, the challenges in obtaining a definitive diagnosis, and the treatment of this disease, in an effort to provide clinicians with an example of the management of such a peculiar entity.

  7. Causal Therapy of Breast Cancer Irrelevant of Age, Tumor Stage and ER-Status: Stimulation of Estrogen Signaling Coupled With Breast Conserving Surgery.

    Science.gov (United States)

    Suba, Zsuzsanna

    2016-01-01

    Results of long-term studies justify that the rate of breast cancer recurrence and tumor-related mortality remains quite unpredictable, regardless of the use of any current therapeutic measures. Since the application of standard therapies, such as surgery, radiation, chemotherapy and antiestrogen administration does not work as might be expected; our therapeutic practice requires thorough rethinking. Published long-term therapeutic results on breast cancer cases were analyzed in correlation with stage at diagnosis, ER-status of tumors and patients' age. The effectiveness of current therapeutic measures was also compared by estimating the rate of tumor-free survival, breast cancer recurrence and breast cancer-specific mortality. Diagnosis and treatment of breast cancer at an early stage cannot improve the rate of tumor-free survival. Poor differentiation of tumors, ER-negativity in particular, defines poor prognosis even after applying aggressive therapies. In patients treated with in situ breast cancer, the recurrence-rate of invasive tumor increased directly with ageing irrespective of tumor size or ER-status at diagnosis. Women who underwent lumpectomy without adjuvant radiation or chemotherapy exhibited significantly better overall and breast cancer specific survival rates than those receiving mastectomy, regardless of stage and ER-status of tumors. Antiestrogen treatment exhibited unforeseeable effectiveness even on targeted ERpositive tumors. Recent patents propose the detection of ESR1-gene amplification or restoration of ER-alpha expression for prediction of effective antiestrogen treatment, suggesting a crucial inhibitory role of estrogen-signaling against tumorgrowth. Estradiol-induced upregulation of estrogen signaling coupled with sparing of the estrogen-rich mammary fatpad are the most effective strategies against breast cancer.

  8. High-intensity focused ultrasound in breast pathology: non-invasive treatment of benign and malignant lesions.

    Science.gov (United States)

    Cavallo Marincola, Beatrice; Pediconi, Federica; Anzidei, Michele; Miglio, Elena; Di Mare, Luisa; Telesca, Marianna; Mancini, Massimiliano; D'Amati, Giulia; Monti, Massimo; Catalano, Carlo; Napoli, Alessandro

    2015-03-01

    Breast neoplasms are one of the leading causes of morbidity and mortality in women. Even if surgery is the treatment of choice, other forms of less invasive radical treatment are desirable. High-intensity focused ultrasound is already established as a valid non-invasive technique that ensures tumor ablation in various organs. The use of ultrasound or magnetic resonance guidance allows having some advantages such as the capability to treat tumors in moving organs or the possibility to have a real-time monitoring of the temperature increase. The aim of this paper is to report the use of high-intensity focused ultrasound technique with ultrasound and magnetic resonance guidance for the ablation of breast tumors, including both benign and malignant lesions.

  9. Tumor-to-breast volume ratio as measured on MRI: a possible predictor of breast-conserving surgery versus mastectomy.

    Science.gov (United States)

    Faermann, Renata; Sperber, Fani; Schneebaum, Schlomo; Barsuk, Daphna

    2014-02-01

    The surgical approach to breast cancer changed dramatically in the past 20 years. The surgical objective today is to remove the tumor, ensuring negative margins and good cosmetic results, and preserving the breast when possible. Magnetic resonance imaging of the breast has become an essential imaging tool prior to surgery, diagnosing additional tumors and assessing tumor extent. Tumor-to-breast volume ratio, an important predictor of breast conservation, can be measured with MRI and may change the surgical decision. To measure the tumor-to-breast volume ratio using MRI in order to assess whether there is a correlation between this ratio and the type of surgery selected (breast-conserving or mastectomy). The volumes of the tumor and the breast and the tumor-to-breast volume ratio were retrospectively calculated using preoperative breast MRI in 76 patients who underwent breast-conserving surgery or mastectomy. Breast-conserving surgery (lumpectomy) was performed in 64 patients and mastectomy in 12. The average tumor-to-breast volume ratio was 0.06 (6%) in the lumpectomy group and 0.30 (30%) in the mastectomy group (P < 0.0001). The tumor-to-breast volume ratio correlated with the type of surgery. As measured on MRI, this ratio is an accurate means of determining the type of surgery best suited for a given patient. It is recommended that MRI-determined tumor-to-breast volume ratio become part of the surgical planning protocol for patients diagnosed with breast cancer.

  10. Detection and identification of mouse mammary tumor virus-like DNA sequences in blood and breast tissues of breast cancer patients.

    Science.gov (United States)

    Naushad, Wasifa; Bin Rahat, Talha; Gomez, Miriam Kathleen; Ashiq, Muhammad Taimoor; Younas, Muhammad; Sadia, Hajra

    2014-08-01

    Mouse mammary tumor virus (MMTV) is a well-known cause of mammary tumors in mice transmitted as endogenous proviruses or exogenously as infectious virions. The hypothesis that a retrovirus homologous to MMTV is involved in human breast cancers has resulted in renewed interest in the etiology of human breast cancer. Therefore, the detection of MMTV-like exogenous sequences in 30-40 % of invasive breast cancer has increased attention towards this hypothesis. To detect the prevalence of MMTV in Pakistani population, 666-bp-long MMTV envelop and 630-bp LTR sequences were amplified from breast cancer patient samples (tissue biopsies and peripheral blood) using mouse with mammary tumor as control. MMTV-like virus env and LTR DNA sequences were detected in 20 and 26 % of breast tumor samples, respectively, from the total of 80 breast cancer patients' blood and tissue samples. No significant association was observed between age, grade of disease, and lymph node involvement with the prevalence of MMTV-like sequences. Our data add to the growing number of studies implicating MMTV-like virus in human breast cancer, but still clear causal association of MMTV to breast cancer remains to be reputable.

  11. Extremely rare borderline phyllodes tumor in the male breast: a case report.

    Science.gov (United States)

    Kim, Jung Gyu; Kim, Shin Young; Jung, Hae Yoen; Lee, Deuk Young; Lee, Jong Eun

    2015-01-01

    Phyllodes tumor of the male breast is an extremely rare disease, and far fewer cases of borderline phyllodes tumors than benign or malignant tumors in the male breast have been reported. We report a case of borderline phyllodes tumor in the male breast with imaging findings of the tumor and pathologic correlation. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Radiologic findings of metastatic tumors to the breast

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sang Heum; Cha, Eun Suk; Park, Jeong Mi; Kim, Hak Hee; Kim, Ji Young; Park, Young Ha; Shinn, Kyung Sub [The Catholic Univ. of Korea College of Medicine, Suwon (Korea, Republic of)

    1999-09-01

    To analyze the radiologic findings of metastatic tumors of the breast. We retrospectively analyzed the findings of mammography (n = 12), ultrasonography (n = 9) and CT (n = 4) of 13 patients with metastatic tumors of the breast. Methods for confirmation were biopsy (n = 8) and clinical follow-up (n = 5). The patient' s ages ranged from 24 to 63 (mean 43)years. Primary malignancies were contralateral breast cancer (n = 3), non-Hodgkin' s lymphoma (n = 3), stomach cancer (n = 2), uterine cervix cancer (n = 1), laryngeal cancer (n = 1), esophageal melanoma (n = 1), malignant thymoma (n 1), and lung cancer (n = 1). Patterns of metastasis from contralateral breast cancer and the stomach cancer were diffuse and infiltrative, while metastasis from other cancers was of the focal mass-forming type. The radiologic findings of metastasis from contralateral breast cancer (n = 3) were diffuse skin thickening and increased density or echogenicity in the medial aspect of the breast, while in cases involving metastasis from stomach cancer (n = 2) radiographs revealed extensive skin thickening, increased density or echogenicity, lymphedema and ipsilateral lymphadenopathy in the left breast. In cases of metastatic tumors to the breast in which focal masses were seen on mammography (n = 7), marginal spiculation or microcalcification of the tumors was not present. In six such cases, ultrasonography revealed well-defined margin, posterior acoustic shadowing or an irregular thick echogenic boundary was not seen. It two patients who underwent CT scanning, well-defined masses with moderate contrast enhancement were present. Radiographs of metastatic tumors to the breast from contralateral breast cancer and stomach cancer showed diffuse infiltration. The metastatic tumors with focal masses showed oval to round, smooth-mar-ginated, well-defined masses without spiculation or microcalcification on mammography, and a well-defined mass without posterior acoustic shadowing or irregular

  13. Contrast-enhanced dedicated breast CT detection of invasive breast cancer preceding mammographic diagnosis

    Directory of Open Access Journals (Sweden)

    Nicolas D. Prionas, MD, PhD

    2015-01-01

    Full Text Available Dedicated breast computed tomography (bCT generates high-resolution, three-dimensional images of the pendent uncompressed breast. Intravenous iodinated contrast during bCT provides additional physiologic information. In this case, a 10.0-mm invasive ductal carcinoma was visualized using contrast-enhanced breast CT one year before mammographic detection. Mammography four months before bCT was negative. The bCT contrast enhancement pattern closely matched the dynamic contrast-enhanced MRI obtained after diagnosis. Lesion enhancement at contrast-enhanced breast CT matched previously published enhancement values of breast cancer. Contrast-enhanced dedicated bCT provided high-resolution tomographic images and physiologic contrast enhancement data that facilitated the detection of an early breast cancer.

  14. Ubc9 promotes breast cell invasion and metastasis in a sumoylation-independent manner.

    Science.gov (United States)

    Zhu, S; Sachdeva, M; Wu, F; Lu, Z; Mo, Y-Y

    2010-03-25

    Ubc9 is an E2-conjugating enzyme that transfers the activated small ubiquitin-like modifier (SUMO) to protein substrates, and thus it has an important function in sumoylation-mediated cellular pathways. We have earlier reported that Ubc9 promotes tumor growth in the xenograft mouse model using breast cancer cell line MCF-7 in part through regulation of Bcl-2 expression. In this study, we show that ectopic expression of wild-type Ubc9 (Ubc9-WT) promotes cell invasion and metastasis. Surprisingly, the dominant negative mutant Ubc9 (Ubc9-DN) also causes the same phenotype, indicating that the ability of Ubc9 to promote invasion and metastasis is distinct from its ability to conjugate SUMO to protein substrates. Of considerable interest, several microRNAs such as miR-224 are regulated by Ubc9. Although ectopic expression of Ubc9 causes downregulation of miR-224, suppression of Ubc9 by Ubc9-siRNAs leads to its upregulation. We further show that miR-224 can inhibit cell invasion and directly targets CDC42 and CXCR4, and that suppression of CDC42 and CXCR4 by RNAi causes inhibition of Ubc9-mediated invasion. Together, these results show a molecular link between Ubc9 and the metastasis genes such as CDC42 and CXCR4, and thus provide new insight into the mechanism by which Ubc9 promotes tumor invasion and metastasis.

  15. Pattern of Ipsilateral Breast Tumor Recurrence After Breast-Conserving Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Jobsen, Jan, E-mail: j.jobsen@mst.nl [Department of Radiation Oncology, Medisch Spectrum Twente, Enschede (Netherlands); Palen, Job van der [Department of Epidemiology, Medisch Spectrum Twente, Enschede (Netherlands); Department of Research Methodology, Measurement, and Data Analysis, Faculty of Behavioral Science, University of Twente, Enschede (Netherlands); Riemersma, Sietske [Laboratory for Pathology Oost Nederland, Hengelo (Netherlands); Heijmans, Harald [Department of Surgery, Ziekenhuis Groep Twente, Hengelo (Netherlands); Ong, Francisca [Department of Radiation Oncology, Medisch Spectrum Twente, Enschede (Netherlands); Struikmans, Henk [Department of Radiation Oncology, Leiden University Medical Centre, Leiden (Netherlands); Radiotherapy Centre West, Medical Centre Haaglanden, The Hague (Netherlands)

    2014-08-01

    Purpose: To analyze the incidence and prognostic factors of ipsilateral breast tumor recurrence (IBTR) after breast-conserving therapy (BCT) in a large, population-based, single-center study with long-term follow-up. Methods and Materials: We analyzed 3595 cases in which BCT was performed in 3824 women with stage I or II breast cancer. The incidence of IBTR was analyzed over time and was based on IBTR as first event. Results: The 15-year local relapse-free survival was 90.9%. The hazard estimates for IBTR showed a time course with 2 peaks, the first at approximately 5 years and the second, twice as high, at 12 years. Stratifying subjects by age and margin status showed that, for women ≤40 years old with negative margins, adjuvant systemic therapy led to a 5-fold reduced risk of recurrence compared to none, and the presence of lymph vascular space invasion (LVSI) had a 3-fold increased risk compared to its absence. For women >40 years old, the presence of LVSI (hazard ratio [HR] 2.5) and the presence of lobular carcinoma in situ in the lumpectomy specimen (HR 2.3) were the only 2 risk factors. Conclusions: We demonstrated a pattern in risk of IBTR over time, with 2 peaks, first at approximately 5 years and a second, much higher peak at approximately 12 years, especially for women ≤40 years old. For women ≤40 years old with tumor-free resection margins, we noted that the absence of adjuvant systemic therapy and the presence of LVSI were independent prognostic factors of IBTR. For women >40 years old, the presence of LVSI and the presence of lobular carcinoma in situ were independent risk factors.

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

    Science.gov (United States)

    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 Pbreast 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 between ER+ lobular and ER+ IDC tumors. These data provide evidence for overlapping, but distinct etiological pathways within ER+ breast cancer between morphological subtypes. PMID:24743323

  17. FSIP1 binds HER2 directly to regulate breast cancer growth and invasiveness.

    Science.gov (United States)

    Liu, Tong; Zhang, Hao; Sun, Li; Zhao, Danyu; Liu, Peng; Yan, Meisi; Zaidi, Neeha; Izadmehr, Sudeh; Gupta, Animesh; Abu-Amer, Wahid; Luo, Minna; Yang, Jie; Ou, Xunyan; Wang, Yining; Bai, Xuefeng; Wang, Yan; New, Maria I; Zaidi, Mone; Yuen, Tony; Liu, Caigang

    2017-07-18

    Fibrous sheath interacting protein 1 (FSIP1), a spermatogenesis-related testicular antigen, is expressed in abundance in breast cancers, particularly in those overexpressing human epidermal growth factor receptor 2 (HER2); however, little is known about its role in regulating the growth and metastasis of breast cancer cells. We and others have shown previously that FSIP1 expression in breast cancer correlates positively with HER2-positivity, recurrence, and metastases and negatively with survival. Here, using coimmunoprecipitation and microscale thermophoresis, we find that FSIP1 binds to the intracellular domain of HER2 directly. We further show that shRNA-induced FSIP1 knockdown in SKBR3 and MCF-7 breast cancer cells inhibits proliferation, stimulates apoptosis, attenuates epithelial-mesenchymal transition, and impairs migration and invasiveness. Consistent with reduced proliferation and enhanced apoptosis, xenotransplantation of SKBR3 cells stably transfected with sh-FSIP1 into nu/nu mice results in reduced tumor volumes compared with sh-NC transplants. Furthermore, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) mapping using sh-FSIP1 gene signature yielded associations with extracellular matrix protein pathways, and a reduction in SNAI2 protein expression was confirmed on Western blot analysis. Complementarily, interrogation of the Connectivity Map using the same gene signature yielded, as top hits, chemicals known to inhibit epithelial-mesenchymal transition, including rapamycin, 17-N-allylamino-17-demethoxygeldanamycin, and LY294002. These compounds phenocopy the effects of sh-FSIP1 on SKBR3 cell viability. Thus, FSIP1 suppression limits oncogenesis and invasiveness in breast cancer cells and, considering its absence in most other tissues, including normal breast, may become a potential target for breast cancer therapy.

  18. Glucocorticoids and histone deacetylase inhibitors cooperate to block the invasiveness of basal-like breast cancer cells through novel mechanisms

    DEFF Research Database (Denmark)

    Law, M E; Corsino, P E; Jahn, S C

    2013-01-01

    Aggressive cancers often express E-cadherin in cytoplasmic vesicles rather than on the plasma membrane and this may contribute to the invasive phenotype of these tumors. Therapeutic strategies are not currently available that restore the anti-invasive function of E-cadherin in cancers. MDA-MB-231...... cells are a frequently used model of invasive triple-negative breast cancer, and these cells express low levels of E-cadherin that is mislocalized to cytoplasmic vesicles. MDA-MB-231 cell lines stably expressing wild-type E-cadherin or E-cadherin fused to glutathione S-transferase or green fluorescent...... protein were used as experimental systems to probe the mechanisms responsible for cytoplasmic E-cadherin localization in invasive cancers. Although E-cadherin expression partly reduced cell invasion in vitro, E-cadherin was largely localized to the cytoplasm and did not block the invasiveness...

  19. Simultaneous loss of the DLC1 and PTEN tumor suppressors enhances breast cancer cell migration

    Energy Technology Data Exchange (ETDEWEB)

    Heering, Johanna; Erlmann, Patrik [University of Stuttgart, Institute of Cell Biology and Immunology, Allmandring 31, 70569 Stuttgart (Germany); Olayioye, Monilola A., E-mail: monilola.olayioye@izi.uni-stuttgart.de [University of Stuttgart, Institute of Cell Biology and Immunology, Allmandring 31, 70569 Stuttgart (Germany)

    2009-09-10

    The phosphatase and tensin homolog (PTEN) gene is a tumor suppressor frequently deleted or mutated in sporadic tumors of the breast, prostate, endometrium and brain. The protein acts as a dual specificity phosphatase for lipids and proteins. PTEN loss confers a growth advantage to cells, protects from apoptosis and favors cell migration. The deleted in liver cancer 1 (DLC1) gene has emerged as a novel tumor suppressor downregulated in a variety of tumor types including those of the breast. DLC1 contains a Rho GTPase activating domain that is involved in the inhibition of cell proliferation, migration and invasion. To investigate how simultaneous loss of PTEN and DLC1 contributes to cell transformation, we downregulated both proteins by RNA interference in the non-invasive MCF7 breast carcinoma cell line. Joint depletion of PTEN and DLC1 resulted in enhanced cell migration in wounding and chemotactic transwell assays. Interestingly, both proteins were found to colocalize at the plasma membrane and interacted physically in biochemical pulldowns and coimmunoprecipitations. We therefore postulate that the concerted local inactivation of signaling pathways downstream of PTEN and DLC1, respectively, is required for the tight control of cell migration.

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

    Directory of Open Access Journals (Sweden)

    Elinor Sawyer

    2014-04-01

    Full Text Available 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

  1. Molecular aspects of tumor cell migration and invasion

    Directory of Open Access Journals (Sweden)

    Giuseppina Bozzuto

    2010-03-01

    Full Text Available Cell migration and invasion are crucial steps in many physiological events. However, they are also implicated in the physiopathology of many diseases, such as cancer. To spread through the tissues, tumor cells use mechanisms that involve several molecular actors: adhesion receptor families, receptor tyrosine kinases, cytoskeleton proteins, adapter and signalling proteins interplay in a complex scenario. The balance of cellular signals for proliferation and survival responses also regulates migratory behaviours of tumor cells. To complicate the scene of crime drug resistance players can interfere thus worsening this delicate situation. The complete understanding of this molecular jungle is an impossible mission: some molecular aspects are reviewed in this paper.

  2. Nerve fibers in breast cancer tissues indicate aggressive tumor progression.

    Science.gov (United States)

    Huang, Di; Su, Shicheng; Cui, Xiuying; Shen, Ximing; Zeng, Yunjie; Wu, Wei; Chen, Jianing; Chen, Fei; He, Chonghua; Liu, Jiang; Huang, Wei; Liu, Qiang; Su, Fengxi; Song, Erwei; Ouyang, Nengtai

    2014-12-01

    Emerging evidence has indicated nerve fibers as a marker in the progression of various types of cancers, such as pancreatic cancer and prostate cancer. However, whether nerve fibers are associated with breast cancer progression remains unclear. In this study, we evaluated the presence of nerve fibers in 352 breast cancer specimens and 83 benign breast tissue specimens including 43 cases of cystic fibrosis and 40 cases of fibroadenoma from 2 independent breast tumor center using immunohistochemical staining for specific peripheral nerve fiber markers.In all, nerve fibers were present in 130 out of 352 breast cancer tissue specimens, while none were detected in normal breast tissue specimens. Among 352 cases, we defined 239 cases from Sun Yat-Sen Memorial Hospital, Guangzhou, China, as the training set, and 113 cases from the First Affiliated Hospital of Shantou University, Guangdong, China, as the validation set. The thickness of tumor-involving nerve fibers is significantly correlated with poor differentiation, lymph node metastasis, high clinical staging, and triple negative subtype in breast cancer. More importantly, Cox multifactor analysis indicates that the thickness of tumor-involving nerve fibers is a previously unappreciated independent prognostic factors associated with shorter disease-free survival of breast cancer patients. Our findings are further validated by online Oncomine database. In conclusion, our results show that nerve fiber involvement in breast cancer is associated with progression of the malignancy and warrant further studies in the future.

  3. Nerve Fibers in Breast Cancer Tissues Indicate Aggressive Tumor Progression

    Science.gov (United States)

    Huang, Di; Su, Shicheng; Cui, Xiuying; Shen, Ximing; Zeng, Yunjie; Wu, Wei; Chen, Jianing; Chen, Fei; He, Chonghua; Liu, Jiang; Huang, Wei; Liu, Qiang; Su, Fengxi; Song, Erwei; Ouyang, Nengtai

    2014-01-01

    Abstract Emerging evidence has indicated nerve fibers as a marker in the progression of various types of cancers, such as pancreatic cancer and prostate cancer. However, whether nerve fibers are associated with breast cancer progression remains unclear. In this study, we evaluated the presence of nerve fibers in 352 breast cancer specimens and 83 benign breast tissue specimens including 43 cases of cystic fibrosis and 40 cases of fibroadenoma from 2 independent breast tumor center using immunohistochemical staining for specific peripheral nerve fiber markers. In all, nerve fibers were present in 130 out of 352 breast cancer tissue specimens, while none were detected in normal breast tissue specimens. Among 352 cases, we defined 239 cases from Sun Yat-Sen Memorial Hospital, Guangzhou, China, as the training set, and 113 cases from the First Affiliated Hospital of Shantou University, Guangdong, China, as the validation set. The thickness of tumor-involving nerve fibers is significantly correlated with poor differentiation, lymph node metastasis, high clinical staging, and triple negative subtype in breast cancer. More importantly, Cox multifactor analysis indicates that the thickness of tumor-involving nerve fibers is a previously unappreciated independent prognostic factors associated with shorter disease-free survival of breast cancer patients. Our findings are further validated by online Oncomine database. In conclusion, our results show that nerve fiber involvement in breast cancer is associated with progression of the malignancy and warrant further studies in the future. PMID:25501061

  4. Clinicopathological variables predicting HER-2 gene status in immunohistochemistry-equivocal (2+) invasive breast cancer.

    Science.gov (United States)

    Ji, Yongling; Sheng, Liming; Du, Xianghui; Qiu, Guoqin; Chen, Bo; Wang, Xiaojia

    2014-07-01

    Human epidermal growth factor receptor-2 (HER-2) gene status is crucial to guide treatment decisions regarding the use of HER-2-targeted therapies in breast cancer. An invasive breast cancer with HER-2 2+ score is regarded as HER-2 status equivocal and should further determine by fluorescent in situ hybridization (FISH), which is considered the standard test for HER-2 status. Here, we aimed to establish a risk score to allow for prediction of the presence of HER-2 gene status. A total of 182 HER-2 2+ by immunohistochemistry (IHC) invasive breast cancer cases were enrolled in this study. The association between clinicopathological variables like age, sex, tumor grade, hormone receptor (HR) status, P53 and proliferation index (Ki67), and FISH result using US Food and Drug Administration (FDA) criteria was evaluated. Also, we compared the HER-2 FISH results using FDA criteria and 2013 American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guideline. The study population had a median age of 48 years (range, 29-78 years). Estrogen receptor (ER) was expressed in 131 (72.0%) patients. 73.1% of patients (133/182) were progesterone receptor (PR) positive. The median Ki67 value was 20% (range, 3-90%). There was good agreement between the FDA and 2013 ASCO/CAP guideline. Sixty-three of all patients were HER-2 FISH amplified (positive) based on FDA criteria. Tumors with HER-2 amplified were more likely to harbor ER negative (58.8% vs. 25.2%, PHER-2 amplified groups (P=0.006). We created a risk score that comprised HR, P53 and Ki67. A significant association between risk score and HER-2 FISH amplification was observed (χ(2)=30.41, PHER-2 gene status in invasive breast cancer.

  5. Recurrent angio-fibroma of breast masquerading as phyllodes tumor.

    Science.gov (United States)

    Chaurasia, Jai K; Alam, Feroz; Shadan, Mariam; Naim, Mohammed

    2015-01-01

    A young Indian female presented with a recurring tumor in the right breast masquerading as phyllodes tumor. Patient had history of five times excision and recurrences of the tumor, diagnosed as fibrous phyllodes of the breast. Presently, a well-circumscribed tumor of about 10 cm size, comprising of benign fibrous-angiomatous tissue with evidence of foci of pyogenic vasculitis was observed. Immuno-histochemical markers for the myo-epithelial and epithelial elements excluded the possibility of fibrous phyllodes, inflammatory myofibroblastic tumor, desmoid fibromatosis, and metaplastic carcinoma. The present findings were diagnostic of an inflammatory angio-fibroma of the right breast, not reported in the earlier literature. The observations indicated that the female breast may be susceptible to spontaneous productive and common-antibiotic-resistant focal septic vascular inflammation giving rise to angio-fibromatous proliferation producing a well-defined tumor mass in the breast, distinguishable from the other breast lesions by the connective tissue stains and immuno-histochemical markers.

  6. Magnetic resonance imaging of benign phyllodes tumors of the breast.

    Science.gov (United States)

    Kinoshita, Takayuki; Fukutomi, Takashi; Kubochi, Kiyoshi

    2004-01-01

    Magnetic resonance imaging (MRI) has the potential to become a useful adjunct in breast imaging. Contrast-enhanced breast MRI has demonstrated a high sensitivity in the detection of benign and malignant breast disease. Our study aimed to correlate the dynamic contrast-enhanced MRI appearance of benign phyllodes tumor of the breast with histopathologic findings. We retrospectively reviewed the MRI findings in eight patients with benign phyllodes tumor of the breast to describe the image characteristics of this disease. The architectural features and enhancement patterns of this tumor were assessed and compared with other breast diseases. MRIs demonstrated some characteristics for large benign phyllodes tumors (more than 3 cm in size). On T(2)-weighted images, they were imaged as spotted tumors in high to iso signal intensity with cystic components or septations inside. In the time-signal intensity curve for the eight patients in our study who underwent dynamic MRI, we demonstrated two patterns of their curve: rapidly and gradually enhanced. In conclusion, MRI findings in benign phyllodes tumor include dynamic curves of gradually and rapidly enhancing types, and a low and inhomogeneous signal intensity on T(2)-weighted images compared with fibroadenoma. These findings appear to be useful for diagnosis.

  7. Phyllodes tumors of the breast: diagnosis, treatment and prognostic factors related to recurrence

    Science.gov (United States)

    Zhou, Zhi-Rui; Wang, Chen-Chen; Yang, Zhao-Zhi

    2016-01-01

    Phyllodes tumors of the breast are rare tumor types that consist of 0.3–1.0% in all breast tumors. The naming and classification of breast phyllodes tumor have been debated for years. Based on the classification criteria modified by WHO in 2003, this review mainly introduced the clinicopathologic characteristics, pre-operational diagnosis and the treatment of breast phyllodes tumors, and also summarized the prognostic factors related to tumor recurrence. PMID:28066617

  8. Breast Cancer Risk Prediction with Heterogeneous Risk Profiles According to Breast Cancer Tumor Markers

    OpenAIRE

    Rosner, Bernard; Glynn, Robert J.; Tamimi, Rulla M.; Chen, Wendy Y.; Colditz, Graham A.; Willett, Walter C.; Hankinson, Susan E.

    2013-01-01

    Relationships between some risk factors and breast cancer incidence are known to vary by tumor subtype. However, breast tumors can be classified according to a number of markers, which may be correlated, making it difficult to identify heterogeneity of risk factors with specific tumor markers when using standard competing-risk survival analysis. In this paper, we propose a constrained competing-risk survival model that allows for assessment of heterogeneity of risk factor associations accordi...

  9. Silencing of tumor suppressor genes RASSF1A, SLIT2, and WIF1 by promoter hypermethylation in hereditary breast cancer.

    Science.gov (United States)

    Alvarez, Carolina; Tapia, Teresa; Cornejo, Valeria; Fernandez, Wanda; Muñoz, Alex; Camus, Mauricio; Alvarez, Manuel; Devoto, Luigi; Carvallo, Pilar

    2013-06-01

    Promoter hypermethylation is gaining strength as one of the main mechanisms through which tumor suppressor genes are silenced during tumor progression. Three tumor suppressor genes are frequently found methylated in their promoter, in concordance with absence of expression, RASSF1A, SLIT2, and WIF1. In addition, a previous array-CGH analysis from our group showed that these genes are found in deleted genomic regions observed in hereditary breast cancer tumors. In the present work we analyzed the methylation status of these three tumor suppressor gene promoters in 47 hereditary breast cancer tumors. Promoter methylation status analysis of hereditary breast tumors revealed high methylation frequencies for the three genes (67% RASSF1A, 80% SLIT2, and 72% WIF1). Additionally, the presence of methylated PCR products was associated with absence of protein expression for the three genes and statistically significant for RASSF1A and WIF1. Interestingly, methylation of all the three genes was found in 4 out of 6 grade I invasive ductal carcinoma tumors. Association between RASSF1A methylation and DCIS tumors was found. These results suggest that silencing of these tumor suppressor genes is an early event in hereditary breast cancer, and could be a marker for pre-malignant phenotypes. Copyright © 2012 Wiley Periodicals, Inc.

  10. Thrombospondin-1 (TSP-1) up-regulates tissue inhibitor of metalloproteinase-1 (TIMP-1) production in human tumor cells: exploring the functional significance in tumor cell invasion.

    Science.gov (United States)

    John, Anitha S; Hu, Xioulong; Rothman, Vicki L; Tuszynski, George P

    2009-12-01

    Thrombospondin-1 (TSP-1), a matrix-bound adhesive glycoprotein, has been shown to modulate tumor progression. We previously demonstrated that TSP-1 up-regulates matrix metalloproteinases MMP-2 and MMP-9. Our studies suggested that the balance between MMPs and tissue inhibitors of metalloproteinases (TIMPs) is a key determinant in tumor cell invasion. We now report that TSP-1 up-regulates TIMP-1 expression in both human breast and prostate cancer cell lines. The effect of TSP-1 on TIMP-1 expression was examined in human breast adenocarcinoma cell lines (MDA-MB-231) and human prostate cancer cell lines (PC3-NI and PC3-ML) treated with exogenous TSP-1. TIMP-1 expression was also examined in TSP-1 stably transfected breast cancer cell line (MDA-MB-435). Northern and western blot analysis revealed TIMP-1 mRNA and TIMP-1 protein expression increased with increasing concentrations of TSP-1. This effect was inhibited by antibodies against the type I repeat domain of TSP-1 further suggesting that TSP-1 mediates TIMP-1 secretion. Inhibition of TSP-1 induced TIMP-1 levels increased tumor cell invasion. We conclude that TSP-1 is involved in influencing the critical balance between MMPs and their inhibitors, maintaining the controlled degradation of the extracellular matrix needed to support metastasis and our results may provide an explanation for the divergent activities reported for TSP-1 in tumor progression.

  11. Cancer-associated adipocytes promotes breast tumor radioresistance

    Energy Technology Data Exchange (ETDEWEB)

    Bochet, Ludivine; Meulle, Aline [Universite de Toulouse, UPS, F-31077 Toulouse Cedex (France); CNRS, IPBS (Institut de Pharmacologie et de Biologie Structurale), 205 route de Narbonne, BP 64182, F-31077 Toulouse Cedex (France); Institut National de la Sante et de la Recherche Medicale, INSERM U1048, 1 Avenue du Pr Jean Poulhes, BP 84225, F-31432 Toulouse Cedex (France); Imbert, Sandrine [CNRS, IPBS (Institut de Pharmacologie et de Biologie Structurale), 205 route de Narbonne, BP 64182, F-31077 Toulouse Cedex (France); Salles, Bernard [Universite de Toulouse, UPS, F-31077 Toulouse Cedex (France); CNRS, IPBS (Institut de Pharmacologie et de Biologie Structurale), 205 route de Narbonne, BP 64182, F-31077 Toulouse Cedex (France); Valet, Philippe [Universite de Toulouse, UPS, F-31077 Toulouse Cedex (France); Institut National de la Sante et de la Recherche Medicale, INSERM U1048, 1 Avenue du Pr Jean Poulhes, BP 84225, F-31432 Toulouse Cedex (France); Muller, Catherine, E-mail: muller@ipbs.fr [Universite de Toulouse, UPS, F-31077 Toulouse Cedex (France); CNRS, IPBS (Institut de Pharmacologie et de Biologie Structurale), 205 route de Narbonne, BP 64182, F-31077 Toulouse Cedex (France)

    2011-07-22

    Highlights: {yields} Tumor-surrounding adipocytes contribute to breast cancer progression. {yields} Breast tumor cells previously co-cultivated with mature adipocytes exhibit radioresistance. {yields} Increased in Chk1 phosphorylation is observed in irradiated co-cultivated tumor cells. {yields} IL-6 is over-expressed in tumor cells co-cultivated with adipocytes. {yields} IL-6 exposure confers increased Chk1 phosphorylation and radioresistance in tumor cells. -- Abstract: Mature adipocytes are excellent candidates to influence tumor behavior through heterotypic signaling processes since these cells produce hormones, growth factors, cytokines and other molecules, a heterogeneous group of molecules named adipokines. Using a 2D coculture system, we demonstrate that breast tumor cells previously co-cultivated with mature adipocytes exhibit radioresistance and an earlier and higher increase in the effector kinase Chk1, a phenotype that was associated with decreased cell death as compared to tumor cells grown alone. Interestingly, the adipocytes-induced tumor changes taking place during the coculture time preceding the exposure to IR were sufficient to confer the radioresistant effect. Notorious among the changes brought by adipocytes was the significant increase of IL-6 expression in tumor cells, whose activity may well account for the observed tumor cell protection from IR toxicity. Indeed, our data confirmed the protective role of this cytokine as tumor cells incubated after irradiation with recombinant IL-6 exhibit an increased in Chk1 phosphorylation and a radioresistant phenotype, thus far recapitulating the effects observed in the presence of adipocytes. Our current study sheds light on a new role of tumor-surrounding adipocytes in fostering a radioresistant phenotype in breast tumors, a finding that might have important clinical implications in obese patients that frequently exhibit aggressive diseases.

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

    DEFF Research Database (Denmark)

    Sawyer, Elinor; Roylance, Rebecca; Petridis, Christos

    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 can...

  13. Ubc9 promotes breast cell invasion and metastasis in a sumoylation-independent manner

    OpenAIRE

    Zhu, Shuomin; Sachdeva, Mohit; Wu, Fangting; Lu, Zhaohui; Mo, Yin-Yuan

    2009-01-01

    Ubc9 is an E2 conjugating enzyme that transfers the activated SUMO (small ubiquitin-related modifier) to protein substrates, and thus it plays a critical role in sumoylation-mediated cellular pathways. We have previously reported that Ubc9 promotes tumor growth in the xenograft mouse model using breast cancer cell line MCF-7 in part through regulation of Bcl-2 expression. In this study, we show that ectopic expression of wild type Ubc9 (Ubc9-WT) promotes cell invasion and metastasis. Surprisi...

  14. Correlation between 3 T apparent diffusion coefficient values and grading of invasive breast carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Cipolla, Valentina, E-mail: valentina.cipolla@yahoo.it [Department of Radiological Sciences, University of Rome “Sapienza”, Viale del Policlinico 155, 00161 Rome (Italy); Santucci, Domiziana; Guerrieri, Daniele; Drudi, Francesco Maria [Department of Radiological Sciences, University of Rome “Sapienza”, Viale del Policlinico 155, 00161 Rome (Italy); Meggiorini, Maria Letizia [Department of Gynaecological Sciences, University of Rome “Sapienza”, Viale del Policlinico 155, 00161 Rome (Italy); Felice, Carlo de [Department of Radiological Sciences, University of Rome “Sapienza”, Viale del Policlinico 155, 00161 Rome (Italy)

    2014-12-15

    Highlights: • Apparent diffusion coefficient is a quantitative parameter which reflects molecular water movement. • Grading is an independent prognostic factor which correlates with other histopathological features. • Apparent diffusion coefficient values were significantly different between G1 and G3 classes. - Abstract: Purpose: The aim of this study was to evaluate whether the apparent diffusion coefficient (ADC) provided by 3.0 T (3 T) magnetic resonance diffusion-weighted imaging (DWI) varied according to the grading of invasive breast carcinoma. Materials and methods: A total of 92 patients with 96 invasive breast cancer lesions were enrolled; all had undergone 3 T magnetic resonance imaging (MRI) for local staging. All lesions were confirmed by histological analysis, and tumor grade was established according to the Nottingham Grading System (NGS). MRI included both dynamic contrast-enhanced and DWI sequences, and ADC value was calculated for each lesion. ADC values were compared with NGS classification using the Mann–Whitney U and the Kruskal–Wallis H tests. Grading was considered as a comprehensive prognostic factor, and Rho Spearman test was performed to determine correlation between grading and tumor size, hormonal receptor status, HER2 expression and Ki67 index. Pearson's Chi square test was carried out to compare grading with the other prognostic factors. Results: ADC values were significantly higher in G1 than in G3 tumors. No significant difference was observed when G1 and G3 were compared with G2. Tumor size, hormonal receptor status, HER2 expression and Ki67 index correlated significantly with grading but there was a significant difference only between G1 and G3 related to the ER and PR status, HER2 expression and Ki67 index. There was no statistically significant difference in lesion size between the two groups. Conclusion: ADC values obtained on 3 T DWI correlated with low-grade (G1) and high-grade (G3) invasive breast carcinoma. 3

  15. ABL tyrosine kinase inhibition variable effects on the invasive properties of different triple negative breast cancer cell lines.

    Directory of Open Access Journals (Sweden)

    Clément Chevalier

    Full Text Available The non-receptor tyrosine kinase ABL drives myeloid progenitor expansion in human chronic myeloid leukemia. ABL inhibition by the tyrosine kinase inhibitor nilotinib is a first-line treatment for this disease. Recently, ABL has also been implicated in the transforming properties of solid tumors, including triple negative (TN breast cancer. TN breast cancers are highly metastatic and several cell lines derived from these tumors display high invasive activity in vitro. This feature is associated with the activation of actin-rich membrane structures called invadopodia that promote extracellular matrix degradation. Here, we investigated nilotinib effect on the invasive and migratory properties of different TN breast cancer cell lines. Nilotinib decreased both matrix degradation and invasion in the TN breast cancer cell lines MDA-MB 231 and MDA-MB 468. However, and unexpectedly, nilotinib increased by two-fold the invasive properties of the TN breast cancer cell line BT-549 and of Src-transformed fibroblasts. Both display much higher levels of ABL kinase activity compared to MDA-MB 231. Similar effects were obtained by siRNA-mediated down-regulation of ABL expression, confirming ABL central role in this process. ABL anti-tumor effect in BT-549 cells and Src-transformed fibroblasts was not dependent on EGF secretion, as recently reported in neck and squamous carcinoma cells. Rather, we identified the TRIO-RAC1 axis as an important downstream element of ABL activity in these cancer cells. In conclusion, the observation that TN breast cancer cell lines respond differently to ABL inhibitors could have implications for future therapies.

  16. Minimal elastographic modeling of breast cancer for model based tumor detection in a digital image elasto tomography (DIET) system

    Science.gov (United States)

    Lotz, Thomas F.; Muller, Natalie; Hann, Christopher E.; Chase, J. Geoffrey

    2011-03-01

    Digital Image Elasto Tomography (DIET) is a non-invasive breast cancer screening technology that images the surface motion of a breast under harmonic mechanical actuation. A new approach capturing the dynamics and characteristics of tumor behavior is presented. A simple mechanical model of the breast is used to identify a transfer function relating the input harmonic actuation to the output surface displacements using imaging data of a silicone phantom. Areas of higher stiffness cause significant changes of damping and resonant frequencies as seen in the resulting Bode plots. A case study on a healthy and tumor silicone breast phantom shows the potential for this model-based method to clearly distinguish cancerous and healthy tissue as well as correctly predicting the tumor position.

  17. Ets2 in tumor fibroblasts promotes angiogenesis in breast cancer.

    Directory of Open Access Journals (Sweden)

    Julie A Wallace

    Full Text Available Tumor fibroblasts are active partners in tumor progression, but the genes and pathways that mediate this collaboration are ill-defined. Previous work demonstrates that Ets2 function in stromal cells significantly contributes to breast tumor progression. Conditional mouse models were used to study the function of Ets2 in both mammary stromal fibroblasts and epithelial cells. Conditional inactivation of Ets2 in stromal fibroblasts in PyMT and ErbB2 driven tumors significantly reduced tumor growth, however deletion of Ets2 in epithelial cells in the PyMT model had no significant effect. Analysis of gene expression in fibroblasts revealed a tumor- and Ets2-dependent gene signature that was enriched in genes important for ECM remodeling, cell migration, and angiogenesis in both PyMT and ErbB2 driven-tumors. Consistent with these results, PyMT and ErbB2 tumors lacking Ets2 in fibroblasts had fewer functional blood vessels, and Ets2 in fibroblasts elicited changes in gene expression in tumor endothelial cells consistent with this phenotype. An in vivo angiogenesis assay revealed the ability of Ets2 in fibroblasts to promote blood vessel formation in the absence of tumor cells. Importantly, the Ets2-dependent gene expression signatures from both mouse models were able to distinguish human breast tumor stroma from normal stroma, and correlated with patient outcomes in two whole tumor breast cancer data sets. The data reveals a key function for Ets2 in tumor fibroblasts in signaling to endothelial cells to promote tumor angiogenesis. The results highlight the collaborative networks that orchestrate communication between stromal cells and tumor cells, and suggest that targeting tumor fibroblasts may be an effective strategy for developing novel anti-angiogenic therapies.

  18. IL-32 promotes breast cancer cell growth and invasiveness.

    Science.gov (United States)

    Wang, Shouman; Chen, Feiyu; Tang, Lili

    2015-01-01

    Interleukin (IL)-32 is a newly identified cytokine in humans and primates. It has been established that IL-32 may antagonize cancer growth. However, to the best of our knowledge, the direct effect of IL-32 on breast cancer cell growth has not yet been investigated. In addition, rodents lack the expression of IL-32; hence, the effects of IL-32 on breast cancer xenografts in nude mice have not been studied. The present study aimed to examine the potential regulatory effects of IL-32 on breast cancer cells in nude mice. The effects of IL-32 on tumor cell growth in cell cuture and a tumor xenograft model were investigated, as well as the effects of IL-32 on apoptosis. The effects of IL-32 on cell proliferation and apoptosis were investigated by MTT assay and TUNEL staining, respectively. The results revealed that IL-32 increases the proliferation rate of cancer cells and decreases the rate of apoptosis, In addition, IL-32 was found to enhance the growth of tumor xenografts in vivo. In summary, IL-32 may represent a useful therapeutic target for human breast cancer.

  19. Is "prepectoral edema" a morphologic sign for malignant breast tumors?

    Science.gov (United States)

    Kaiser, Clemens G; Herold, Michael; Baltzer, Pascal A T; Dietzel, Matthias; Krammer, Julia; Gajda, Mieczyslaw; Camara, Oumar; Schoenberg, Stefan O; Kaiser, Werner A; Wasser, Klaus

    2015-06-01

    A variety of morphologic and kinetic signs of benign or malignant breast lesions contribute to a final diagnosis and differential diagnosis in magnetic resonance (MR) mammography (MRM). As a new sign, prepectoral edema (PE) in patients without any history of previous biopsy, operation, radiation, or chemotherapy was detected during routine breast MR examinations. The purpose of this study was to retrospectively evaluate the role of this morphologic sign in the differential diagnosis of breast lesions. Between January 2005 and October 2006, a total of 1109 consecutive MRM examinations have been performed in our institution. In this study, only patients who would later be biopsied or operated in our own hospital were included. They had no previous operation, biopsy, intervention, chemotherapy, hormone replacement therapy, or previous mastitis. In total, 162 patients with 180 lesions were included, histologically correlated later-on by open biopsy (124 patients and 136 lesions) or core biopsy (38 patients and 44 lesions). The evaluations were performed by four experienced radiologists in consensus. One hundred eighty evaluated lesions included 104 malignant lesions (93 invasive and 11 noninvasive cancers) and 76 benign lesions. PE was detected in 2.6% of benign lesions (2 of 76), in none of the Ductal cacinoma in situ (DCIS) cases (0 of 11), and in 25.8% of malignant lesions (24 of 93; P 2 cm in diameter (48.5%, 17 of 35 vs. 13.8%, 8 of 58; P < .001). PE was not statistically associated to malignant tumor type, presence or absence of additional DCIS, and number of lesions. This resulted in the following diagnostic parameters for PE as an indicator for malignancy: sensitivity of 19.3%, specificity of 97.3%, positive predictive value (PPV) of 92.3%, negative predictive value of 48%, and accuracy of 57.7%. In case of occurrence, the "PE sign" seems to be a specific indicator for malignant tumors with a high PPV, independent from its entity. Copyright © 2015 AUR

  20. Interplay of Stem Cell Characteristics, EMT, and Microtentacles in Circulating Breast Tumor Cells

    Energy Technology Data Exchange (ETDEWEB)

    Charpentier, Monica [Program in Molecular Medicine, University of Maryland School of Medicine, 655 W. Baltimore St., Bressler Bldg., Rm 10-20, Baltimore, MD 21201 (United States); Marlene and Stewart Greenebaum National Cancer Institute Cancer Center, University of Maryland School of Medicine, 655 W. Baltimore St., Bressler Bldg., Rm 10-29, Baltimore, MD 21201 (United States); Martin, Stuart, E-mail: ssmartin@som.umaryland.edu [Marlene and Stewart Greenebaum National Cancer Institute Cancer Center, University of Maryland School of Medicine, 655 W. Baltimore St., Bressler Bldg., Rm 10-29, Baltimore, MD 21201 (United States); Department of Physiology, University of Maryland School of Medicine, 655 W. Baltimore St., Bressler Bldg., Rm 10-29, Baltimore, MD 21201 (United States)

    2013-11-14

    Metastasis, not the primary tumor, is responsible for the majority of breast cancer-related deaths. Emerging evidence indicates that breast cancer stem cells (CSCs) and the epithelial-to-mesenchymal transition (EMT) cooperate to produce circulating tumor cells (CTCs) that are highly competent for metastasis. CTCs with both CSC and EMT characteristics have recently been identified in the bloodstream of patients with metastatic disease. Breast CSCs have elevated tumorigenicity required for metastatic outgrowth, while EMT may promote CSC character and endows breast cancer cells with enhanced invasive and migratory potential. Both CSCs and EMT are associated with a more flexible cytoskeleton and with anoikis-resistance, which help breast carcinoma cells survive in circulation. Suspended breast carcinoma cells produce tubulin-based extensions of the plasma membrane, termed microtentacles (McTNs), which aid in reattachment. CSC and EMT-associated upregulation of intermediate filament vimentin and increased detyrosination of α-tubulin promote the formation of McTNs. The combined advantages of CSCs and EMT and their associated cytoskeletal alterations increase metastatic efficiency, but understanding the biology of these CTCs also presents new therapeutic targets to reduce metastasis.

  1. A comparative study of four serological tumor markers for the detection of breast cancer.

    Science.gov (United States)

    Clinton, Shawn R; Beason, Kevin L; Bryant, Sabrina; Johnson, James T; Jackson, Margaret; Wilson, Cynthia; Holifield, Kay; Vincent, Charlton; Hall, Margot

    2003-01-01

    Breast cancer is currently the third most common cause of cancer in the world. Circulating tumor antigens are often used as a minimally invasive tool for noting breast cancer progression. The objective of this study was to compare four tumor antigens (CA 15-3, CA 27.29, alpha-fetoprotein [AFP], and carcinoembryonic antigen [CEA]) for their diagnostic efficacy in breast cancer patients. It was hypothesized that CA 15-3 would proved to be superior to CA 27.29, CEA, and AFP in assay performance. Tumor marker assays were performed according to the manufacturers' directions. Assays used in this study were CA 15-3 and CA 27.29 (Fujirebio Diagnostics/Centocor Inc.), AFP (Abbott Inc.), and CEA (Hybritech Inc.). A total of 554 patient samples were obtained from an area hospital, plus 200 healthy adult samples which were used for the determination of normal reference intervals. The patients included patients with no disease (184), with non-malignant disease (11), with breast cancer (87), and with other types of cancer (272). Diagnostic percent sensitivities for each marker were: CA 15-3 (63%), CA 27.29 (39%), CEA (22%), and AFP (22%). Diagnostic specificities for each marker were comparable, ranging from 80-88%. Analytical parameters were evaluated for the assays and compared favorably. We concluded that CA 15-3 was the best tumor antigen for use as a diagnostic aid and monitoring agent.

  2. Mucocele-like tumor and columnar cell hyperplasia of the breast occurring in a morphologic continuum

    Directory of Open Access Journals (Sweden)

    Fadare Oluwole

    2008-04-01

    Full Text Available Abstract Introduction Mucocele-like tumor was originally described in 1986 as a benign breast proliferation consisting of multiple dilated cysts lined by cytologically bland, flat to cuboidal cells. Subsequent reports described the coexistence of, including the morphologic inter-transitions between, mucocele-like tumor and a variety of other breast proliferations, including intraductal carcinoma, invasive carcinoma, atypical ductal hyperplasia, and hyperplasia of the usual type. The spectrum of breast alterations characterized by variably enlarged terminal-ductal lobular units lined by variably hyperplastic and variably atypical columnar cells has been the subject of significant discussion in the recent literature. In one scheme, these lesions may be classified into four groups, that is, columnar cell change with and without atypia and columnar cell hyperplasia with and without atypia. Morphologic and molecular observations suggest an association, perhaps in a nonobligate precursor role, between some columnar cell lesions and a variety of other neoplastic lesions. Case presentation We describe the case of a 43-year-old woman whose breast tumor contained areas diagnostic of mucocele-like tumor and columnar cell hyperplasia, with morphologic transitions in between. Conclusion Our case represents the second broadly similar case that has been reported, and suggests a potential relationship between these two enigmatic lesions.

  3. Ganodermanontriol (GDNT) exerts its effect on growth and invasiveness of breast cancer cells through the down-regulation of CDC20 and uPA

    Energy Technology Data Exchange (ETDEWEB)

    Jiang, Jiahua; Jedinak, Andrej [Cancer Research Laboratory, Methodist Research Institute, Indiana University Health, Indianapolis, IN (United States); Sliva, Daniel, E-mail: dsliva@iuhealth.org [Cancer Research Laboratory, Methodist Research Institute, Indiana University Health, Indianapolis, IN (United States); Department of Medicine, School of Medicine, Indiana University, Indianapolis, IN (United States); Indiana University Simon Cancer Center, School of Medicine, Indiana University, Indianapolis, IN (United States)

    2011-11-18

    Highlights: Black-Right-Pointing-Pointer Ganodermanontriol (GDNT), a Ganoderma mushroom alcohol, inhibits growth of breast cancer cells. Black-Right-Pointing-Pointer CDC20 is over-expressed in tumors but not in the tumor surrounding tissue in breast cancer patients. Black-Right-Pointing-Pointer GDNT inhibits expression of CDC20 in breast cancer cells. Black-Right-Pointing-Pointer GDNT inhibits cell adhesion, cell migration and cell invasion of breast cancer cells. Black-Right-Pointing-Pointer GDNT inhibits secretion of uPA and down-regulates expression of uPAR in breast cancer cells. -- Abstract: Ganoderma lucidum is a medicinal mushroom that has been recognized by Traditional Chinese Medicine (TCM). Although some of the direct anticancer activities are attributed to the presence of triterpenes-ganoderic and lucidenic acids-the activity of other compounds remains elusive. Here we show that ganodermanontriol (GDNT), a Ganoderma alcohol, specifically suppressed proliferation (anchorage-dependent growth) and colony formation (anchorage-independent growth) of highly invasive human breast cancer cells MDA-MB-231. GDNT suppressed expression of the cell cycle regulatory protein CDC20, which is over-expressed in precancerous and breast cancer cells compared to normal mammary epithelial cells. Moreover, we found that CDC20 is over-expressed in tumors when compared to the tissue surrounding the tumor in specimens from breast cancer patients. GDNT also inhibited invasive behavior (cell adhesion, cell migration, and cell invasion) through the suppression of secretion of urokinase-plasminogen activator (uPA) and inhibited expression of uPA receptor. In conclusion, mushroom GDNT is a natural agent that has potential as a therapy for invasive breast cancers.

  4. The Reproducibility of Nuclear Morphometric Measurements in Invasive Breast Carcinoma

    Directory of Open Access Journals (Sweden)

    Pauliina Kronqvist

    1997-01-01

    Full Text Available The intraobserver and interobserver reproducibility of computerized nuclear morphometry was determined in repeated measurements of 212 samples of invasive breast cancer. The influence of biological variation and the selection of the measurement area was also tested. Morphometrically determined mean nuclear profile area (Pearson’s r 0.89, grading efficiency (GE 0.95 and standard deviation (SD of nuclear profile area (Pearson’s r 0.84, GE 0.89 showed high reproducibility. In this respect, nuclear morphometry equals with other established methods of quantitative pathology and exceeds the results of subjective grading of nuclear atypia in invasive breast cancer. A training period of eight days was sufficient to produce clear improvement in consistency of nuclear morphometry results. By estimating the sources of variation it could be shown that the variation associated with the measurement procedure itself is small. Instead, sample associated variation is responsible for the majority of variation in the measurements (82.9% in mean nuclear profile area and 65.9% in SD of nuclear profile area. This study points out that when standardized methods are applied computerized morphometry is a reproducible and reliable method of assessing nuclear atypia in invasive breast cancer. For further improvement special emphasize should be put on sampling rules of selecting the microscope fields and measurement areas.

  5. How to approach phyllodes tumors of the breast?

    Science.gov (United States)

    Acar, Turan; Tarcan, Ercüment; Hacıyanlı, Mehmet; Kamer, Erdinç; Peşkersoy, Mustafa; Yiğit, Seyran; Gür, Özlem; Cin, Necat; Sarı, Ayşegül Akder; Tatar, Fatma

    2015-01-01

    Objective: Phyllodes tumor of the breast is a rare fibroepithelial breast tumor that comprise 0.3–0.9% of primary breast neoplasms. In this study, we aimed to present clinicopathologic symptoms of our patients along with their treatment modality. Material and Methods: Clinicopathologic properties and treatment modality of 20 phyllodes tumor patients who underwent surgery between January 2008 and January 2013 were retrospectively evaluated. Results: Median patient age was 47 years (22–75). Fine-needle aspiration biopsy was applied to 19 patients. Biopsy results were reported as suspicious in four, malignant in three, benign in 11, and as non-diagnostic in one patient. Final histopathology reports revealed two benign, one malignant and one borderline tumor out of the four patients with suspicious findings on fine needle aspiration biopsy; all patients with malignant cytology had malignancy. There were two borderline and nine benign lesions within the benign biopsy group. Sixteen patients underwent segmental mastectomy, four patients underwent mastectomy with/without axillary dissection. The median tumor size was 6 (1–13) cm. Histopathologically, 11 (55%) tumors were benign, 5 (25%) were borderline, and 4 (20%) were malignant. Two of the four patients with malignancy underwent radiotherapy and chemotherapy, and one patient only received chemotherapy as adjuvant treatment. Conclusion: Phyllodes tumors are rare, mix-type breast tumors. Due to high rates of local recurrence and potential for malignancy, preoperative diagnosis and accurate management are important. PMID:26668526

  6. Cytotoxicity and anti-tumor effects of new ruthenium complexes on triple negative breast cancer cells.

    Directory of Open Access Journals (Sweden)

    Cecília P Popolin

    Full Text Available Triple-negative breast cancer (TNBC is a highly aggressive breast cancer subtype. The high rate of metastasis associated to the fact that these cells frequently display multidrug resistance, make the treatment of metastatic disease difficult. Development of antitumor metal-based drugs was started with the discovery of cisplatin, however, the severe side effects represent a limitation for its clinical use. Ruthenium (Ru complexes with different ligands have been successfully studied as prospective antitumor drugs. In this work, we demonstrated the activity of a series of biphosphine bipyridine Ru complexes (1 [Ru(SO4(dppb(bipy], (2 [Ru(CO3(dppb(bipy], (3 [Ru(C2O4(dppb(bipy] and (4 [Ru(CH3CO2(dppb(bipy]PF6 [where dppb = 1,4-bis(diphenylphosphinobutane and bipy = 2,2'-bipyridine], on proliferation of TNBC (MDA-MB-231, estrogen-dependent breast tumor cells (MCF-7 and a non-tumor breast cell line (MCF-10A. Complex (4 was most effective among the complexes and was selected to be further investigated on effects on tumor cell adhesion, migration, invasion and in apoptosis. Moreover, DNA and HSA binding properties of this complex were also investigated. Results show that complex (4 was more efficient inhibiting proliferation of MDA-MB-231 cells over non-tumor cells. In addition, complex (4 was able to inhibit MDA-MB231 cells adhesion, migration and invasion and to induce apoptosis and inhibit MMP-9 secretion in TNBC cells. Complex (4 should be further investigated in vivo in order to stablish its potential to improve breast cancer treatment.

  7. DEGRO practical guidelines: radiotherapy of breast cancer II. Radiotherapy of non-invasive neoplasia of the breast

    Energy Technology Data Exchange (ETDEWEB)

    Souchon, R. [University Hospital Tuebingen, Klinik fuer Radioonkologie, Tuebingen (Germany); Sautter-Bihl, M.L. [Municipal Hospital Karlsruhe, Karlsruhe (Germany); Sedlmayer, F. [LKH Salzburg, Paracelsus Medical University Hospital, Salzburg (Austria); Budach, W. [University Hospital Duesseldorf, Duesseldorf (Germany); Dunst, J. [University Hospital Schleswig-Holstein, Luebeck (Germany); Feyer, P. [Klinikum Neukoelln, Berlin (Germany); Fietkau, R.; Sauer, R. [University Hospital Erlangen, Erlangen (Germany); Harms, W. [St. Clara Hospital, Basel (Switzerland); Wenz, F. [University Hospital Mannheim, Mannheim (Germany); Haase, W.

    2014-01-15

    . Randomized clinical trials and a huge number of mostly observational studies have unanimously demonstrated that RT significantly reduces recurrence risks of ipsilateral DCIS as well as invasive breast cancer independent of patient age in all subgroups. The recommended total dose is 50 Gy administered as whole breast irradiation (WBI) in single fractions of 1.8 or 2.0 Gy given on 5 days weekly. Retrospective data indicate a possible beneficial effect of an additional tumor bed boost for younger patients. Prospective clinical trials of different dose-volume concepts (hypofractionation, accelerated partial breast irradiation, boost radiotherapy) are still ongoing. Postoperative radiotherapy permits breast conservation for the majority of women by halving local recurrence as well as reducing progression rates into invasive cancer. New data confirmed this effect in all patient subsets - even in low risk subgroups (LoE 1a). (orig.) [German] Aktualisierung und Ergaenzung der 2007 von der DEGRO-Expertengruppe Mammakarzinom publizierten Leitlinie zur Radiotherapie (RT) des Mammakarzinoms. Aufgrund der zunehmenden klinischen Relevanz nicht-invasiver epithelialer Neoplasien der Brust wurde diesen in der aktuellen Version ein eigenes Kapitel gewidmet. Schwerpunkte der hier vorgelegten Empfehlungen sind - in Ergaenzung zu den S3-Leitlinien der Deutschen Krebsgesellschaft von 2012 - die Indikation und Technik der postoperativen RT nach brusterhaltender Operation. Die DEGRO-Expertengruppe fuehrte eine Literaturrecherche aktueller klinisch kontrollierter Studien, systematischer Reviews und Metaanalysen, orientiert an den Kriterien der evidenzbasierten Medizin, im Hinblick auf neue Aspekte gegenueber 2005 und 2007 durch. Die Recherche umfasst die Zeitspanne 2008 bis September 2012 und erstreckte sich auf in PubMed und Guidelines International Network (G-I-N) gelisteten Publikationen. Suchbegriffe waren ''non invasive breast cancer'', ''ductal carcinoma in situ

  8. Blood vessel endothelium-directed tumor cell streaming in breast tumors requires the HGF/C-Met signaling pathway.

    Science.gov (United States)

    Leung, E; Xue, A; Wang, Y; Rougerie, P; Sharma, V P; Eddy, R; Cox, D; Condeelis, J

    2017-05-11

    During metastasis to distant sites, tumor cells migrate to blood vessels. In vivo, breast tumor cells utilize a specialized mode of migration known as streaming, where a linear assembly of tumor cells migrate directionally towards blood vessels on fibronectin-collagen I-containing extracellular matrix (ECM) fibers in response to chemotactic signals. We have successfully reconstructed tumor cell streaming in vitro by co-plating tumors cells, macrophages and endothelial cells on 2.5 μm thick ECM-coated micro-patterned substrates. We found that tumor cells and macrophages, when plated together on the micro-patterned substrates, do not demonstrate sustained directional migration in only one direction (sustained directionality) but show random bi-directional walking. Sustained directionality of tumor cells as seen in vivo was established in vitro when beads coated with human umbilical vein endothelial cells were placed at one end of the micro-patterned 'ECM fibers' within the assay. We demonstrated that these endothelial cells supply the hepatocyte growth factor (HGF) required for the chemotactic gradient responsible for sustained directionality. Using this in vitro reconstituted streaming system, we found that directional streaming is dependent on, and most effectively blocked, by inhibiting the HGF/C-Met signaling pathway between endothelial cells and tumor cells. Key observations made with the in vitro reconstituted system implicating C-Met signaling were confirmed in vivo in mammary tumors using the in vivo invasion assay and intravital multiphoton imaging of tumor cell streaming. These results establish HGF/C-Met as a central organizing signal in blood vessel-directed tumor cell migration in vivo and highlight a promising role for C-Met inhibitors in blocking tumor cell streaming and metastasis in vivo, and for use in human trials.

  9. Active Roles of Tumor Stroma in Breast Cancer Metastasis

    Directory of Open Access Journals (Sweden)

    Zahraa I. Khamis

    2012-01-01

    Full Text Available Metastasis is the major cause of death for breast cancer patients. Tumors are heterogenous cellular entities composed of cancer cells and cells of the microenvironment in which they reside. A reciprocal dynamic interaction occurs between the tumor cells and their surrounding stroma under physiological and pathological conditions. This tumor-host communication interface mediates the escape of tumor cells at the primary site, survival of circulating cancer cells in the vasculature, and growth of metastatic cancer at secondary site. Each step of the metastatic process is accompanied by recruitment of stromal cells from the microenvironment and production of unique array of growth factors and chemokines. Stromal microenvironment may play active roles in breast cancer metastasis. Elucidating the types of cells recruited and signal pathways involved in the crosstalk between tumor cells and stromal cells will help identify novel strategies for cotargeting cancer cells and tumor stromal cells to suppress metastasis and improve patient outcome.

  10. Is it useful to detect lymphovascular invasion in lymph node-positive patients with primary operable breast cancer?

    Science.gov (United States)

    Ragage, Florence; Debled, Marc; MacGrogan, Gaëtan; Brouste, Véronique; Desrousseaux, Marie; Soubeyran, Isabelle; de Lara, Christine Tunon; Mauriac, Louis; de Mascarel, Isabelle

    2010-07-01

    Lymphovascular invasion (LVI) is a widely recognized prognostic factor in lymph node-negative breast cancers. However, there are only limited and controversial data about its prognostic significance in lymph node-positive patients. Among 931 patients operated on and monitored at the authors' institution for an invasive breast carcinoma between 1989 and 1992, all 374 lymph node-positive breast cancers entered the study (median follow-up, 126 months). LVI was present in 46% of tumors and was associated with age < or = 40 years (P = .02), high histological grade (P = .01), and negative estrogen receptor status (P = .032), but not with tumor size, number of involved lymph nodes, or HER-2/neu status. LVI was an independent prognostic factor for distant metastases (P = .002). Furthermore, in HER-2/neu-negative/hormone receptor-positive (n = 287) tumors, the number of independent prognostic factors (LVI, age, histological grade, number of involved lymph nodes, and tumor size) was associated with a 5-years metastasis-free survival ranging from 100% if no factors (n = 25) to 89% +/- 2% if 1 or 2 factors (n = 186) and 67% +/- 6 if 3, 4, or 5 factors (n = 76) were present (P < .001). LVI is an independent prognostic factor in lymph node-positive breast cancer and merits further prospective investigations as a decision tool in the adjuvant chemotherapy setting.

  11. Mammographic evidence of microenvironment changes in tumorous breasts.

    Science.gov (United States)

    Marin, Zach; Batchelder, Kendra A; Toner, Brian C; Guimond, Lyne; Gerasimova-Chechkina, Evgeniya; Harrow, Amy R; Arneodo, Alain; Khalil, Andre

    2017-04-01

    The microenvironment of breast tumors plays a critical role in tumorigenesis. As long as the structural integrity of the microenvironment is upheld, the tumor is suppressed. If tissue structure is lost through disruptions in the normal cell cycle, the microenvironment may act as a tumor promoter. Therefore, the properties that distinguish between healthy and tumorous tissues may not be solely in the tumor characteristics but rather in surrounding non-tumor tissue. The goal of this paper was to show preliminary evidence that tissue disruption and loss of homeostasis in breast tissue microenvironment and breast bilateral asymmetry can be quantitatively and objectively assessed from mammography via a localized, wavelet-based analysis of the whole breast. A wavelet-based multifractal formalism called the 2D Wavelet Transform Modulus Maxima (WTMM) method was used to quantitate density fluctuations from mammographic breast tissue via the Hurst exponent (H). Each entire mammogram was cut in hundreds of 360 × 360 pixel subregions in a gridding scheme of overlapping sliding windows, with each window boundary separated by 32 pixels. The 2D WTMM method was applied to each subregion individually. A data mining approach was set up to determine which metrics best discriminated between normal vs. cancer cases. These same metrics were then used, without modification, to discriminate between normal vs. benign and benign vs. cancer cases. The density fluctuations in healthy mammographic breast tissue are either monofractal anti-correlated (H 1/2) for dense tissue. However, tissue regions with H~1/2, as well as left vs. right breast asymetries, were found preferably in tumorous (benign or cancer) breasts vs. normal breasts, as quantified via a combination metric yielding a P-value ~ 0.0006. No metric considered showed significant differences between cancer vs. benign breasts. Since mammographic tissue regions associated with uncorrelated (H~1/2) density fluctuations were

  12. Background parenchymal enhancement in breast MRIs of breast cancer patients: impact on tumor size estimation.

    Science.gov (United States)

    Baek, Ji Eun; Kim, Sung Hun; Lee, Ah Won

    2014-08-01

    To evaluate whether the degree of background parenchymal enhancement affects the accuracy of tumor size estimation based on breast MRI. Three hundred and twenty-two patients who had known breast cancer and underwent breast MRIs were recruited in our study. The total number of breast cancer cases was 339. All images were assessed retrospectively for the level of background parenchymal enhancement based on the BI-RADS criteria. Maximal lesion diameters were measured on the MRIs, and tumor types (mass vs. non-mass) were assessed. Tumor size differences between the MRI-based estimates and estimates based on pathological examinations were analyzed. The relationship between accuracy and tumor types and clinicopathologic features were also evaluated. The cases included minimal (47.5%), mild (28.9%), moderate (12.4%) and marked background parenchymal enhancement (11.2%). The tumors of patients with minimal or mild background parenchymal enhancement were more accurately estimated than those of patients with moderate or marked enhancement (72.1% vs. 56.8%; p=0.003). The tumors of women with mass type lesions were significantly more accurately estimated than those of the women with non-mass type lesions (81.6% vs. 28.6%; penhancement is related to the inaccurate estimation of tumor size based on MRI. Non-mass type breast cancer and HER2-positive breast cancer are other factors that may cause inaccurate assessment of tumor size. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  13. Studies on the relationship of pleiotrophin and MMP2 with the clinicopathological features of invasive breast carcinoma

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    Bo ZHANG

    2012-08-01

    Full Text Available Objective To study the correlation between the expressions of both pleitropin (PTN and matrix metalloproteinase-2 (MMP2 to the clinicopathological features of patients with breast cancer. Methods The pathological specimens were collected from 103 cases of invasive breast cancer, including 51 cases of triple negative breast cancer (TNBC, i.e. all the estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 were negatively expressed and 52 cases of non-TNBC. Ten specimens of paraneoplastic tissue were also collected as controls. The expressions of PTN and MMP2 were detected with immunohistochemical method, and the correlation of PTN and MMP2 expressions to the clinicopathological features of breast cancer (age, tumor size, histopathological grading and axillary lymph node metastases was assessed. Results Among the 103 patients with breast cancer, no statistical difference was found between TNBC group and non-TNBC group in age of onset, tumor size and the axillary lymph node metastasis (P > 0.05, but significant difference was found in histopathological grading (P < 0.05. The positive rate of PTN expression was 83.5% (86/103, and of MMP2 expression was 68% (70/103, and no significant difference was found between TNBC group and non-TNBC group. The expressions of PTN and MMP2 were correlated with the age of onset, histopathological grading and axillary lymph node metastasis, but showed poor consistency in breast cancer (Kappa coefficient=0.1817, 95% CI=-0.0091-0.3726; Z=2.0212, P=0.0433. Conclusions The expression of PTN and MMP2 is correlated with the age, histopathological grading and axillary lymph node metastasis of patients with invasive breast cancer, and not correlated with TNBC. The expression of PTN and MMP2 shows poor consistency in invasive breast cancer.

  14. "Ruptured" malignant phyllodes tumor of the breast: a case report

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    Ditsatham C

    2016-02-01

    Full Text Available Chagkrit Ditsatham, Areewan Somwangprasert, Kirati Watcharachan, Phanchaporn WongmaneerungDivision of Head, Neck and Breast, Department of Surgery, Chiang Mai University, Chiang Mai, ThailandAbstract: Phyllodes tumor or cystosarcoma phyllodes is a rare disease and is usually seen in middle-aged patients. Ruptured phyllodes tumor is a very rare condition. Our study reports patient presentation, diagnosis method, and treatment of an unusual case. A 58-year-old premenopausal female was diagnosed with a phyllodes tumor and presented with a rapidly growing mass for 2 months that ruptured 1 month later. She underwent simple mastectomy at the left side of her breast and received adjuvant radiotherapy. No recurrence was found 4 months after operation.Keywords: ruptured, malignant, phyllodes tumor, breast 

  15. Phyllodes Tumor of the Breast Metastasizing to the Vulva

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    Olusegun Kayode Ajenifuja

    2015-01-01

    Full Text Available Phyllodes tumors of the breast are rare breast tumors that resemble fibroadenoma. They are composed of two types of tissues: stromal and glandular tissues. Unlike fibroadenoma, they are commonly found in the third decade of life and they tend to grow more rapidly. Depending on the relative components of the cells and mitotic activity, they are classified into benign, borderline, and malignant. They are usually present as a lump in the breast. Phyllodes tumors are usually managed by wide excision. The excision should be wide enough to ensure a tumor-free margin. Recurrence rate is very high and most recurrences are usually local. Metastasis to the vulva has not been reported.

  16. HMGA1: a master regulator of tumor progression in triple-negative breast cancer cells.

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    Sandeep N Shah

    Full Text Available Emerging evidence suggests that tumor cells metastasize by co-opting stem cell transcriptional networks, although the molecular underpinnings of this process are poorly understood. Here, we show for the first time that the high mobility group A1 (HMGA1 gene drives metastatic progression in triple negative breast cancer cells (MDA-MB-231, Hs578T by reprogramming cancer cells to a stem-like state. Silencing HMGA1 expression in invasive, aggressive breast cancer cells dramatically halts cell growth and results in striking morphologic changes from mesenchymal-like, spindle-shaped cells to cuboidal, epithelial-like cells. Mesenchymal genes (Vimentin, Snail are repressed, while E-cadherin is induced in the knock-down cells. Silencing HMGA1 also blocks oncogenic properties, including proliferation, migration, invasion, and orthotopic tumorigenesis. Metastatic progression following mammary implantation is almost completely abrogated in the HMGA1 knock-down cells. Moreover, silencing HMGA1 inhibits the stem cell property of three-dimensional mammosphere formation, including primary, secondary, and tertiary spheres. In addition, knock-down of HMGA1 depletes cancer initiator/cancer stem cells and prevents tumorigenesis at limiting dilutions. We also discovered an HMGA1 signature in triple negative breast cancer cells that is highly enriched in embryonic stem cells. Together, these findings indicate that HMGA1 is a master regulator of tumor progression in breast cancer by reprogramming cancer cells through stem cell transcriptional networks. Future studies are needed to determine how to target HMGA1 in therapy.

  17. Tumor suppressor genes are frequently methylated in lymph node metastases of breast cancers

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    Xu Jia

    2010-07-01

    Full Text Available Abstract Introduction Metastasis represents a major adverse step in the progression of breast carcinoma. Lymph node invasion is the most relevant prognostic factor; however little is known on the molecular events associated with lymph node metastasis process. This study is to investigate the status and role of methylation in lymph node metastatic tumors. Materials and methods Bisulfite pyrosequencing is used to screen 6 putative tumor suppressor genes (HIN-1, RASSF1A, RIL, CDH13, RARβ2 and E-cadherin in 38 pairs of primary breast tumors and lymph node metastases. Results We found that HIN-1, CDH13, RIL, RASSF1A and RARβ2 were frequently methylated both in primary and metastatic tissues (range: 55.3%~89.5%. E-cadherin was not frequently methylated in either setting (range: 18.4%~23.7%. The methylation status of HIN-1, CDH13, RIL, and RARβ2 in lymph nodes metastasis were correlated with that in primary tumors. The Pearson correlation values ranged from 0.624 to 0.472 (p values HIN-1 methylation and hormone status in metastatic lymph nodes. Hypermethylation of HIN-1 in metastasis lymph nodes was significantly associated with expression of ER (odds ratio, 1.070; P = 0.024 and with PR (odds ratio, 1.046; P = 0.026. Conclusions This study suggests that hypermethylation of tumor suppressor genes is extended from primary to metastatic tumors during tumor progression.

  18. Expression Pattern of a Homeotic Gene, HOXA5, in Normal Breast and in Breast Tumors

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    Gregory S. Henderson

    2006-01-01

    Full Text Available Introduction: Homeotic (HOX gene products are now known to be functionally associated with breast cancer biogenesis. Recent evidence has indicated that HOXA5 regulates both p53 and progesterone receptor expression levels in breast cancer cells. In addition, HOXA5 has been shown to interact and regulate the activity of another protein referred to as Twist. As homeotic genes play a pivotal role in development, we sought to decipher the expression pattern in both normal breast tissues and in breast carcinomas. Methods: RT-PCR and immunohistochemistry were performed, to assay the levels of HOXA5 expression, on a panel of normal breast tissue and its corresponding primary breast tumors. Results and Conclusions: We show that HOXA5 expression was maintained at stable levels at different reproductive stages of a woman's life, except during lactation. This evidence indicates that HOXA5 may play a role in maintaining the differentiated state within the breast epithelium. However, nearly 70% of all breast carcinomas had decreased HOXA5 protein levels as compared to normal breast tissues. In addition, we demonstrate that HOXA5 protein expression levels in breast carcinomas inversely co-relates with Epidermal Growth Factor Receptor (EGFR expression. Furthermore, we found that the survival rate amongst the different low levels of HOXA5 expressing breast tumors was not significant, indicative of an early tumorigenesis process in the absence of innate levels of HOXA5 in normal breast cells.

  19. Epithelial periostin expression is correlated with poor survival in patients with invasive breast carcinoma.

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    Ga-Eon Kim

    Full Text Available Invasion and metastasis are direct causes of mortality in patients with breast cancer and require reciprocal interactions between cancer cells and the extracellular matrix (ECM. Periostin, a fasciclin-containing adhesive ECM glycoprotein, is frequently overexpressed in various types of human cancer, and its overexpression in cancer-associated stroma and/or cancer cells is usually associated with poor clinical outcomes. However, the expression of periostin in the successive steps of breast tumorigenesis and its association with outcome variables have not been well established in breast carcinoma. The present study aimed to assess the role of periostin alteration in breast tumorigenesis and evaluate the putative prognostic value of periostin as a function of its compartmentalization. Immunohistochemical staining with anti-periostin antibody was performed in a total of 300 patients (26 patients with normal breast tissues, 76 patients with ductal carcinoma in situ [DCIS], and 198 patients with invasive breast carcinoma [IBC] using tissue microarray. Periostin immunoreactivity was assessed in both epithelial tissue and the surrounding stromal compartment. The mRNA and protein expression of periostin were analyzed in 10 paired normal/invasive cancer frozen specimens by quantitative real time-polymerase chain reaction and western blot analysis, respectively. In cancer tissues, periostin mRNA and protein expression were increased compared with adjacent normal tissues. Both epithelial and stromal periostin staining scores significantly increased in a stepwise manner with disease progression from normal breast tissue to DCIS and IBC (P = 0.000 and 0.000, respectively. High epithelial and stromal periostin expression was observed in 109/189 (57.7% and 158/189 (83.6% cases of IBC, respectively. High epithelial periostin expression was more frequently observed in the distant metastatic relapse-positive group than in the distant metastatic relapse

  20. ADAM12 produced by tumor cells rather than stromal cells accelerates breast tumor progression

    DEFF Research Database (Denmark)

    Frohlich, Camilla; Nehammer, Camilla; Albrechtsen, Reidar

    2011-01-01

    Expression of ADAM12 is low in most normal tissues, but is markedly increased in numerous human cancers, including breast carcinomas. We have previously shown that overexpression of ADAM12 accelerates tumor progression in a mouse model of breast cancer (PyMT). In the present study, we found...

  1. The Potential Role of Hedgehog Signaling in the Luminal/Basal Phenotype of Breast Epithelia and in Breast Cancer Invasion and Metastasis

    Energy Technology Data Exchange (ETDEWEB)

    Flemban, Arwa [Department of Biological, Biomedical and Analytical Sciences, Faculty of Health and Applied Sciences, University of West of England, Bristol BS16 1QY (United Kingdom); Department of Pathology, Faculty of Medicine, Umm Al-Qura University, Makkah 24382 (Saudi Arabia); Qualtrough, David, E-mail: david.qualtrough@uwe.ac.uk [Department of Biological, Biomedical and Analytical Sciences, Faculty of Health and Applied Sciences, University of West of England, Bristol BS16 1QY (United Kingdom)

    2015-09-16

    The epithelium of the lactiferous ducts in the breast is comprised of luminal epithelial cells and underlying basal myoepithelial cells. The regulation of cell fate and transit of cells between these two cell types remains poorly understood. This relationship becomes of greater importance when studying the subtypes of epithelial breast carcinoma, which are categorized according to their expression of luminal or basal markers. The epithelial mesenchymal transition (EMT) is a pivotal event in tumor invasion. It is important to understand mechanisms that regulate this process, which bears relation to the normal dynamic of epithelial/basal phenotype regulation in the mammary gland. Understanding this process could provide answers for the regulation of EMT in breast cancer, and thereby identify potential targets for therapy. Evidence points towards a role for hedgehog signaling in breast tissue homeostasis and also in mammary neoplasia. This review examines our current understanding of role of the hedgehog-signaling (Hh) pathway in breast epithelial cells both during breast development and homeostasis and to assess the potential misappropriation of Hh signals in breast neoplasia, cancer stem cells and tumor metastasis via EMT.

  2. Invasive Lobular Carcinoma of the Breast: Appearance on Digital Breast Tomosynthesis.

    Science.gov (United States)

    Grubstein, Ahuva; Rapson, Yael; Morgenstern, Sara; Gadiel, Itai; Haboosheh, Amit; Yerushalmi, Rinat; Cohen, Maya

    2016-10-01

    The aim of this study was to characterize the signs of invasive lobular carcinoma of the breast on digital breast tomosynthesis (DBT) imaging. The study group included 23 women with pathologically proven invasive lobular carcinoma of the breast for whom both digital mammography (DM) and DBT images were available. The images were read jointly by 2 experienced breast radiologists. Findings were recorded according to the descriptors in the Breast Imaging and Reporting Data System lexicon and correlated with the detailed pathology results. In 21 of the 23 patients, the combination of DM and DBT yielded pathologic findings (91%). Architectural distortions or spiculations were demonstrated in 87% of cases. The addition of DBT to DM improved lesion detection by more clearly depicting both the lesion margins and architectural distortions. Only 2 lesions were occult by both DM and DBT, including 1 lesion in a peripheral location that was not incorporated in the standard mediolateral oblique and craniocaudal views. DBT improves the detection of invasive lobular carcinoma lesions by more clearly depicting architectural distortions and spiculations.

  3. Tumor antigens as proteogenomic biomarkers in invasive ductal carcinomas

    DEFF Research Database (Denmark)

    Olsen, Lars Rønn; Campos, Benito; Winther, Ole

    2014-01-01

    . Similarly, the use of proteomics methods for the discovery of cancer biomarkers is increasing. The emerging field of proteogenomics seeks to enrich the value of genomics and proteomics approaches by studying the intersection of genomics and proteomics data. This task is challenging due to the complex nature...... of transcriptional and translation regulatory mechanisms and the disparities between genomic and proteomic data from the same samples. In this study, we have examined tumor antigens as potential biomarkers for breast cancer using genomics and proteomics data from previously reported laser capture microdissected ER...

  4. Identification of H-Ras-Specific Motif for the Activation of Invasive Signaling Program in Human Breast Epithelial Cells

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    Hae-Young Yong

    2011-02-01

    Full Text Available Increased expression and/or activation of H-Ras are often associated with tumor aggressiveness in breast cancer. Previously, we showed that H-Ras, but not N-Ras, induces MCF10A human breast epithelial cell invasion and migration, whereas both H-Ras and N-Ras induce cell proliferation and phenotypic transformation. In an attempt to determine the sequence requirement directing the divergent phenotype induced by H-Ras and N-Ras with a focus on the induction of human breast cell invasion, we investigated the structural and functional relationships between H-Ras and N-Ras using domain-swap and site-directed mutagenesis approaches. Here, we report that the hypervariable region (HVR, consisting of amino acids 166 to 189 in H-Ras, determines the invasive/migratory signaling program as shown by the exchange of invasive phenotype by swapping HVR sequences between H-Ras and N-Ras. We also demonstrate that the H-Ras-specific additional palmitoylation site at Cys184 is not responsible for the signaling events that distinguish between H-Ras and N-Ras. Importantly, this work identifies the C-terminal HVR, especially the flexible linker domain with two consecutive proline residues Pro173 and Pro174, as a critical domain that contributes to activation of H-Ras and its invasive potential in human breast epithelial cells. The present study sheds light on the structural basis for the Ras isoform-specific invasive program of breast epithelial cells, providing information for the development of agents that specifically target invasion-related H-Ras pathways in human cancer.

  5. RKIP Inhibits Local Breast Cancer Invasion by Antagonizing the Transcriptional Activation of MMP13.

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    Ila Datar

    Full Text Available Raf Kinase Inhibitory Protein or RKIP was initially identified as a Raf-1 binding protein using the yeast 2-hybrid screen. RKIP inhibits the activation phosphorylation of MEK by Raf-1 by competitively inhibiting the binding of MEK to Raf-1 and thus exerting an inhibitory effect on the Raf-MEK-Erk pathway. RKIP has been identified as a metastasis suppressor gene. Expression of RKIP is low in cancer metastases. Although primary tumor growth remains unaffected, re- expression of RKIP inhibits cancer metastasis. Mechanistically, RKIP constrains metastasis by inhibiting angiogenesis, local invasion, intravasation, and colonization. The molecular mechanism of how RKIP inhibits these individual steps remains undefined. In our present study, using an unbiased PCR based screening and by analyzing DNA microarray expression datasets we observe that the expression of multiple metalloproteases (MMPs including MMP1, MMP3, MMP10 and MMP13 are negatively correlated with RKIP expression in breast cancer cell lines and clinical samples. Since expression of MMPs by cancer cells is important for cancer metastasis, we hypothesize that RKIP may mediate suppression of breast cancer metastasis by inhibiting multiple MMPs. We show that the expression signature of RKIP and MMPs is better at predicting high metastatic risk than the individual gene. Using a combination of loss- and gain-of-function approaches, we find that MMP13 is the cause of RKIP-mediated inhibition of local cancer invasion. Interestingly expression of MMP13 alone is not sufficient to reverse the inhibition of breast cancer cell metastasis to the lung due to the expression of RKIP. We find that RKIP negatively regulates MMP13 through the Erk2 signaling pathway and the repression of MMP13 by RKIP is transcription factor AP-1 independent. Together, our findings indicate that RKIP inhibits cancer cell invasion, in part, via MMP13 inhibition. These data also implicate RKIP in the regulation of MMP

  6. Invasive micropapillary carcinoma of the breast: MR imaging findings

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    Lim, Hyo Soon; Jeong, Seo In; Choi, You Ri; Kim, Jin Woong; Lee, Ji Shin; Park, Min Ho [Chonnam National University Medical School, Chonnam National University Hwasun Hospital, Hwasun (Korea, Republic of); Kuzmiak, Cherie M. [Department of Radiology, University of North Carolina, Chapel Hill (Korea, Republic of)

    2013-08-15

    To analyze the magnetic resonance (MR) imaging findings of invasive micropapillary carcinoma of the breast. MR images were retrospectively evaluated in 14 patients (age range: 37-67, mean age: 49 years) with pathologically confirmed invasive micropapillary carcinoma of the breast. The enhancement type (mass/non-mass), shape, margin, contrast enhancement, and time-intensity curve pattern on the dynamic study were correlated with the histopathologic features. Associated findings, such as edema, nipple change, skin change and enlarged axillary lymph nodes were also studied. The most common features of the masses were irregular shape (12 of 14 patients, 85.8%) and irregular or spiculated margin (11 of 14 patients, 78.7%). The contrast enhancement was heterogeneous in 11 patients (78.7%), rim enhancement in 2 cases (14.2%), and homogeneous in one patient (7.1%). The predominant kinetic pattern was rapid increase (14 of 14, 100%) in the initial phase and washout (11 of 14, 78.7%) in the delayed phase. Associated non-mass like enhancement was shown in 4 patients, representing ductal carcinoma in situ. MR imaging helped detect additional sites of cancer other than the index lesion in 3 patients (21.4%). Enlarged axillary lymphadenopathy was identified in 7 of the 14 patients (50%). Invasive micropapillary carcinoma appears as a mass with an irregular shape, irregular or spiculated margin and heterogeneous enhancement on MR imaging. Though these findings are not specific and are also observed with other breast malignancies, invasive micropapillary carcinoma frequently showed multiple lesions, accompanying non-mass enhancement and axillary lymph node enlargement.

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

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    Ellen Ackerstaff

    2007-03-01

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

  8. Associations of Breast Cancer Risk Factors With Tumor Subtypes: A Pooled Analysis From the Breast Cancer Association Consortium Studies

    Science.gov (United States)

    Chang-Claude, Jenny; Goode, Ellen L.; Couch, Fergus J.; Nevanlinna, Heli; Milne, Roger L.; Gaudet, Mia; Schmidt, Marjanka K.; Broeks, Annegien; Cox, Angela; Fasching, Peter A.; Hein, Rebecca; Spurdle, Amanda B.; Blows, Fiona; Driver, Kristy; Flesch-Janys, Dieter; Heinz, Judith; Sinn, Peter; Vrieling, Alina; Heikkinen, Tuomas; Aittomäki, Kristiina; Heikkilä, Päivi; Blomqvist, Carl; Lissowska, Jolanta; Peplonska, Beata; Chanock, Stephen; Figueroa, Jonine; Brinton, Louise; Hall, Per; Czene, Kamila; Humphreys, Keith; Darabi, Hatef; Liu, Jianjun; Van ‘t Veer, Laura J.; van Leeuwen, Flora E.; Andrulis, Irene L.; Glendon, Gord; Knight, Julia A.; Mulligan, Anna Marie; O’Malley, Frances P.; Weerasooriya, Nayana; John, Esther M.; Beckmann, Matthias W.; Hartmann, Arndt; Weihbrecht, Sebastian B.; Wachter, David L.; Jud, Sebastian M.; Loehberg, Christian R.; Baglietto, Laura; English, Dallas R.; Giles, Graham G.; McLean, Catriona A.; Severi, Gianluca; Lambrechts, Diether; Vandorpe, Thijs; Weltens, Caroline; Paridaens, Robert; Smeets, Ann; Neven, Patrick; Wildiers, Hans; Wang, Xianshu; Olson, Janet E.; Cafourek, Victoria; Fredericksen, Zachary; Kosel, Matthew; Vachon, Celine; Cramp, Helen E.; Connley, Daniel; Cross, Simon S.; Balasubramanian, Sabapathy P.; Reed, Malcolm W. R.; Dörk, Thilo; Bremer, Michael; Meyer, Andreas; Karstens, Johann H.; Ay, Aysun; Park-Simon, Tjoung-Won; Hillemanns, Peter; Arias Pérez, Jose Ignacio; Rodríguez, Primitiva Menéndez; Zamora, Pilar; Benítez, Javier; Ko, Yon-Dschun; Fischer, Hans-Peter; Hamann, Ute; Pesch, Beate; Brüning, Thomas; Justenhoven, Christina; Brauch, Hiltrud; Eccles, Diana M.; Tapper, William J.; Gerty, Sue M.; Sawyer, Elinor J.; Tomlinson, Ian P.; Jones, Angela; Kerin, Michael; Miller, Nicola; McInerney, Niall; Anton-Culver, Hoda; Ziogas, Argyrios; Shen, Chen-Yang; Hsiung, Chia-Ni; Wu, Pei-Ei; Yu, Jyh-Cherng; Chen, Shou-Tung; Hsu, Giu-Cheng; Haiman, Christopher A.; Henderson, Brian E.; Le Marchand, Loic; Kolonel, Laurence N.; Lindblom, Annika; Margolin, Sara; Jakubowska, Anna; Lubiński, Jan; Huzarski, Tomasz; Byrski, Tomasz; Górski, Bohdan; Gronwald, Jacek; Hooning, Maartje J.; Hollestelle, Antoinette; van den Ouweland, Ans M. W.; Jager, Agnes; Kriege, Mieke; Tilanus-Linthorst, Madeleine M. A.; Collée, Margriet; Wang-Gohrke, Shan; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Mononen, Kari; Grip, Mervi; Hirvikoski, Pasi; Winqvist, Robert; Mannermaa, Arto; Kosma, Veli-Matti; Kauppinen, Jaana; Kataja, Vesa; Auvinen, Päivi; Soini, Ylermi; Sironen, Reijo; Bojesen, Stig E.; Dynnes Ørsted, David; Kaur-Knudsen, Diljit; Flyger, Henrik; Nordestgaard, Børge G.; Holland, Helene; Chenevix-Trench, Georgia; Manoukian, Siranoush; Barile, Monica; Radice, Paolo; Hankinson, Susan E.; Hunter, David J.; Tamimi, Rulla; Sangrajrang, Suleeporn; Brennan, Paul; McKay, James; Odefrey, Fabrice; Gaborieau, Valerie; Devilee, Peter; Huijts, P.E.A.; Tollenaar, RAEM.; Seynaeve, C.; Dite, Gillian S.; Apicella, Carmel; Hopper, John L.; Hammet, Fleur; Tsimiklis, Helen; Smith, Letitia D.; Southey, Melissa C.; Humphreys, Manjeet K.; Easton, Douglas; Pharoah, Paul; Sherman, Mark E.; Garcia-Closas, Montserrat

    2011-01-01

    Background Previous studies have suggested that breast cancer risk factors are associated with estrogen receptor (ER) and progesterone receptor (PR) expression status of the tumors. Methods We pooled tumor marker and epidemiological risk factor data from 35 568 invasive breast cancer case patients from 34 studies participating in the Breast Cancer Association Consortium. Logistic regression models were used in case–case analyses to estimate associations between epidemiological risk factors and tumor subtypes, and case–control analyses to estimate associations between epidemiological risk factors and the risk of developing specific tumor subtypes in 12 population-based studies. All statistical tests were two-sided. Results In case–case analyses, of the epidemiological risk factors examined, early age at menarche (≤12 years) was less frequent in case patients with PR− than PR+ tumors (P = .001). Nulliparity (P = 3 × 10−6) and increasing age at first birth (P = 2 × 10−9) were less frequent in ER− than in ER+ tumors. Obesity (body mass index [BMI] ≥ 30 kg/m2) in younger women (≤50 years) was more frequent in ER−/PR− than in ER+/PR+ tumors (P = 1 × 10−7), whereas obesity in older women (>50 years) was less frequent in PR− than in PR+ tumors (P = 6 × 10−4). The triple-negative (ER−/PR−/HER2−) or core basal phenotype (CBP; triple-negative and cytokeratins [CK]5/6+ and/or epidermal growth factor receptor [EGFR]+) accounted for much of the heterogeneity in parity-related variables and BMI in younger women. Case–control analyses showed that nulliparity, increasing age at first birth, and obesity in younger women showed the expected associations with the risk of ER+ or PR+ tumors but not triple-negative (nulliparity vs parity, odds ratio [OR] = 0.94, 95% confidence interval [CI] = 0.75 to 1.19, P = .61; 5-year increase in age at first full-term birth, OR = 0.95, 95% CI = 0.86 to 1.05, P = .34; obesity in younger women, OR = 1.36, 95

  9. Genetic and epigenetic silencing of the beclin 1 gene in sporadic breast tumors

    Directory of Open Access Journals (Sweden)

    Wu Yiqing

    2010-03-01

    Full Text Available Abstract Background Beclin 1, an important autophagy-related protein in human cells, is involved in cell death and cell survival. Beclin 1 mapped to human chromosome 17q21. It is widely expressed in normal mammary epithelial cells. Although down-regulated expression with mono-allelic deletions of beclin 1 gene was frequently observed in breast tumors, whether there was other regulatory mechanism of beclin 1 was to be investigated. We studied the expression of beclin 1 and explored the possible regulatory mechanisms on its expression in breast tumors. Methods 20 pairs of tumors and adjacent normal tissues from patients with sporadic breast invasive ductal cancer (IDCs were collected. The mRNA expression of beclin 1 was detected by real-time quantitative RT-PCR. Loss of heterozygosity (LOH was determined by real-time quantitative PCR and microsatellite methods. The protein expression of beclin 1, p53, BRCA1 and BRCA2 was assessed by immunohistochemistry. CpG islands in 5' genomic region of beclin 1 gene were identified using MethylPrimer Program. Sodium bisulfite sequencing was used in examining the methylation status of each CpG island. Results Decreased beclin 1 mRNA expression was detected in 70% of the breast tumors, and the protein levels were co-related to the mRNA levels. Expression of beclin 1 mRNA was demonstrated to be much higher in the BRCA1 positive tumors than that in the BRCA1 negative ones. Loss of heterozygosity was detected in more than 45% of the breast tumors, and a dense cluster of CpG islands was found from the 5' end to the intron 2 of the beclin 1 gene. Methylation analysis showed that the promoter and the intron 2 of beclin 1 were aberrantly methylated in the tumors with decreased expression. Conclusions These data indicated that LOH and aberrant DNA methylation might be the possible reasons of the decreased expression of beclin 1 in the breast tumors. The findings here shed some new light on the regulatory mechanisms of

  10. Inhibition of proliferative and invasive capacities of breast cancer cells by arginine-glycine-aspartic acid peptide in vitro.

    Science.gov (United States)

    Yang, Wanhua; Meng, Li; Wang, Hui; Chen, Rui; Wang, Rui; Ma, Xiangyi; Xu, Gang; Zhou, Jianfeng; Wang, Shixuan; Lu, Yunping; Ma, Ding

    2006-01-01

    The Arg-Gly-Asp (RGD) sequence was selected by using phage-display peptides to target tumors, focusing on targeting alpha(v) integrins in tumor blood vessels. Recent studies suggest that peptides containing the RGD sequence can bind to tumor cells, as well as tumor endothelial cells. To investigate whether the RGD peptide has other effects on tumor cells expressing alpha(v) integrins, besides its tumor targeting capability, we designed and synthesized a 10-amino peptide that contained the RGD sequence in a cyclic conformation with a disulfide bond, which specifically bound to breast cancer cell lines MDA-MB-231 and MCF-7. We found that this RGD peptide, GCGGRGDGGC, inhibited tumor cell proliferation in a dose-dependent manner, and also induced apoptosis and G1-phase cell cycle arrest in both of the cell lines that bound and internalized the peptide. Normal ovarian epithelial cells, which did not bind the RGD peptide, were unaffected. RGD peptide treatment also reduced cell invasiveness in both cell lines in vitro. This study suggests that the RGD peptide not only possesses tumor targeting capacity, but also has direct tumor cytotoxic and invasiveness inhibition effects dependent on the blockage of alpha(v) integrin activity, which would make it more efficient in tumor targeting therapy.

  11. Serum total PSA and free PSA in breast tumors.

    Science.gov (United States)

    Dash, Prakruti; Pati, Sanghamitra; Mangaraj, Manaswini; Sahu, Pratima Kumari; Mohapatra, Prakash Chandra

    2011-04-01

    Now a days measurement of molecular forms of PSA has gained importance in clinical practice. Several studies have demonstrated the production of PSA in female tissues, such as breast. The present piece of work has been undertaken with an objective to estimate the relative proportion of the molecular forms of PSA in serum along with serum testosterone in benign and malignant breast tumor cases and to analyze their association with the severity of the disease process 34 malignant and 26 benign breast disease cases along with 33 healthy controls of same age group were enrolled in this study for evaluation. Serum testosterone was measured by ELISA, whereas serum total PSA (TPSA) and free PSA (FPSA) were estimated by electrochemiluminescence immunoassay. A significant rise of fasting plasma glucose along with prominent dyslipidemia was observed in breast tumor cases. Marked rise in serum testosterone as well as TPSA and FPSA was documented in both benign and malignant breast tumor cases. Serum testosterone revealed a significant positive association with both TPSA and FPSA pointing towards an etiological association between them. However, surgical removal of tumor mass resulted in a marked decline of presurgical value of both TPSA and FPSA with a non-significant fall in serum testosterone revealing tumor tissue as the source of FPSA and TPSA. Thus, estimation of PSA provides prognostic information that may assist in future treatment.

  12. Invasive Pleomorphic Lobular Carcinoma of the Breast: Pathologic, Clinical, and Therapeutic Considerations.

    Science.gov (United States)

    Al-Baimani, Khalid; Bazzarelli, Amy; Clemons, Mark; Robertson, Susan J; Addison, Christina; Arnaout, Angel

    2015-12-01

    Pleomorphic lobular carcinoma is an uncommon form of breast cancer and a subtype of invasive lobular carcinoma. It has unique histopathologic features that translate to a more aggressive phenotype with an associated poor prognosis. Unlike classical invasive lobular carcinoma, it can lose estrogen and progesterone receptor expression and demonstrate HER-2/neu amplification. It remains to be determined, however, whether the pleomorphic histology independently predicts a worse outcome or whether other known associated negative prognostic factors such as larger tumor size, increased metastatic disease, and associated worse molecular subtypes commonly present in pleomorphic carcinoma account for the poor prognosis. Here we present an updated review of the unique pathologic and clinical features of pleomorphic lobular carcinoma needed to guide management for women with this subtype of cancer. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Comparison of tumor-infiltrating lymphocytes between primary and metastatic tumors in breast cancer patients.

    Science.gov (United States)

    Ogiya, Rin; Niikura, Naoki; Kumaki, Nobue; Bianchini, Giampaolo; Kitano, Shigehisa; Iwamoto, Takayuki; Hayashi, Naoki; Yokoyama, Kozue; Oshitanai, Risa; Terao, Mayako; Morioka, Toru; Tsuda, Banri; Okamura, Takuho; Saito, Yuki; Suzuki, Yasuhiro; Tokuda, Yutaka

    2016-12-01

    The presence of tumor-infiltrating lymphocytes (TILs) is associated with favorable long-term outcome in breast cancer. However, little is known about changes in TILs during metastatic progression. To confirm our hypothesis that malignant tumors escape from the host immune system during metastasis, we evaluated the percentage of TILs in paired samples of primary and metastatic breast tumors. We retrospectively identified 25 patients with human epidermal growth factor receptor-2 (HER2 + , n = 14) and triple negative (TN, n = 11) early breast cancer diagnosed between 1990 and 2009 at Tokai University Hospital (Isehara, Japan) and who subsequently experienced regional or distant recurrence confirmed by tumor biopsy/resection. Hematoxylin-eosin-stained slides of these paired samples were evaluated for stromal TILs. Immunohistochemical staining was carried out using primary antibodies against CD4, CD8, Foxp3, programmed cell death ligand 1 (PD-L1), PD-L2, and HLA class I for characterizing the TILs and breast tumors. The percentage of TILs in the primary tumors was significantly higher (average 34.6%) than that in metastatic tumors (average 15.7%) (paired t-test, P = 0.004) and that of CD8 + and CD4 + T cells significantly decreased from primary to metastatic tumors (paired t-test, P = 0.008 and P = 0.026, respectively). The PD-L1, PD-L2, and HLA class I antibody expression changed from positive to negative and vice versa from the primary to the metastatic tumors. Tumors at first metastatic recurrence in HER2 + and TN breast cancers have a lower percentage of TILs and CD8 + and CD4 + T cells compared to primary tumors, which indicates that immune escape plays a role in tumor progression. © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  14. Breast Cancer Stem Cells and Tumor Suppressor Genes

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    Wendy W. Hwang-Verslues

    2008-10-01

    Full Text Available Studies of breast cancer stem cells are in their infancy and many fundamental questions have yet to be fully addressed. The molecular distinction between normal and cancerous breast stem cells is not clear. While there have been recent breakthroughs in mouse mammary stem cells and lineage determination in mammary glands, little has been determined in human cells. Microarray analyses have provided molecular categorization of breast cancer. However, the cellular origin of different types of breast cancer is largely unknown. In addition, the relationship between breast cancer stem cells and mammary progenitor cells has yet to be clarified. One of the key questions is how a normal mammary stem cell becomes a breast cancer stem cell. Importantly, the existence of different types of human breast cancers with distinct pathologic and molecular signatures suggests the possibility that different types of breast cancer stem cells may exist. Here, we aim to review the current evidence for the existence of different subtypes of breast cancer stem cells and provide further insight into how tumor suppressors might be involved in the initiation of breast cancer stem cells.

  15. Analysis of patients with phyllodes tumor of the breast.

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    Atalay, Can; Kınaş, Volkan; Çelebioğlu, Sait

    2014-01-01

    The diagnosis and management of phyllodes tumors is challenging due to its low incidence. The treatment of these tumors is surgery, however the extent of surgery, the application of adjuvant chemotherapy and radiotherapy are still controversial. Therefore, we aimed to evaluate patients who were treated with a diagnosis of phyllodes tumor of the breast in our clinic. Patients who were treated with a diagnosis of phyllodes tumor of the breast between June 2011 and June 2013 were reviewed retrospectively. Patient demographic characteristics (age, gender), menopausal status, symptoms, radiologic and surgical methods used for diagnosis and treatment, histopathologic features of the tumor and type of adjuvant therapy were evaluated. Patients were grouped as benign or borderline/malignant according to histopathological diagnosis. Patients in these groups were compared in terms of age, menopausal status, tumor size and the number of mitosis within the tumor. The median age was 26 years (17-59), and 30 patients were female. The surgical treatment of choice was wide local excision with tumor-free surgical margins in 29 patients and mastectomy in one patient. Histopathological diagnosis after surgery was benign in 21 patients (70%), borderline in 6 patients (20%) and malignant phyllodes tumor in 3 patients (10%). Patients with borderline and malignant phyllodes tumors were significantly older (p=0.002) and had higher mitotic counts (pphyllodes tumors and menopausal status (p=0.06) or tumor size (p=0.1). Surgery is the treatment of choice for phyllodes tumors, and obtaining tumor-free margins is important. Since phyllodes tumors might recur as borderline/malignant tumors, local control with surgery and adjuvant radiotherapy should be provided when required. In this way, distant metastases and death that may arise due to possible malignant recurrences might be avoided.

  16. Genomic aberrations in normal tissue adjacent to HER2-amplified breast cancers: field cancerization or contaminating tumor cells?

    Science.gov (United States)

    Sadanandam, Anguraj; Lal, Aseem; Benz, Stephen C; Eppenberger-Castori, Serenella; Scott, Gary; Gray, Joe W; Spellman, Paul; Waldman, Fred; Benz, Christopher C

    2012-12-01

    Field cancerization effects as well as isolated tumor cell foci extending well beyond the invasive tumor margin have been described previously to account for local recurrence rates following breast conserving surgery despite adequate surgical margins and breast radiotherapy. To look for evidence of possible tumor cell contamination or field cancerization by genetic effects, a pilot study (Study 1: 12 sample pairs) followed by a verification study (Study 2: 20 sample pairs) were performed on DNA extracted from HER2-positive breast tumors and matching normal adjacent mammary tissue samples excised 1-3 cm beyond the invasive tumor margin. High-resolution molecular inversion probe (MIP) arrays were used to compare genomic copy number variations, including increased HER2 gene copies, between the paired samples; as well, a detailed histologic and immunohistochemical (IHC) re-evaluation of all Study 2 samples was performed blinded to the genomic results to characterize the adjacent normal tissue composition bracketing the DNA-extracted samples. Overall, 14/32 (44 %) sample pairs from both studies produced genome-wide evidence of genetic aberrations including HER2 copy number gains within the adjacent normal tissue samples. The observed single-parental origin of monoallelic HER2 amplicon haplotypes shared by informative tumor-normal pairs, as well as commonly gained loci elsewhere on 17q, suggested the presence of contaminating tumor cells in the genomically aberrant normal samples. Histologic and IHC analyses identified occult 25-200 μm tumor cell clusters overexpressing HER2 scattered in more than half, but not all, of the genomically aberrant normal samples re-evaluated, but in none of the genomically normal samples. These genomic and microscopic findings support the conclusion that tumor cell contamination rather than genetic field cancerization represents the likeliest cause of local clinical recurrence rates following breast conserving surgery, and mandate caution

  17. Tumor-associated macrophages: unwitting accomplices in breast cancer malignancy.

    Science.gov (United States)

    Williams, Carly Bess; Yeh, Elizabeth S; Soloff, Adam C

    Deleterious inflammation is a primary feature of breast cancer. Accumulating evidence demonstrates that macrophages, the most abundant leukocyte population in mammary tumors, have a critical role at each stage of cancer progression. Such tumor-associated macrophages facilitate neoplastic transformation, tumor immune evasion and the subsequent metastatic cascade. Herein, we discuss the dynamic process whereby molecular and cellular features of the tumor microenvironment act to license tissue-repair mechanisms of macrophages, fostering angiogenesis, metastasis and the support of cancer stem cells. We illustrate how tumors induce, then exploit trophic macrophages to subvert innate and adaptive immune responses capable of destroying malignant cells. Finally, we discuss compelling evidence from murine models of cancer and early clinical trials in support of macrophage-targeted intervention strategies with the potential to dramatically reduce breast cancer morbidity and mortality.

  18. Non-invasive Detection of Breast Cancer Lymph Node Metastasis using Carbonic Anhydrases IX and XII Targeted Imaging Probes

    Science.gov (United States)

    Tafreshi, Narges K.; Bui, Marilyn M.; Bishop, Kellsey; Lloyd, Mark C.; Enkemann, Steven A.; Lopez, Alexis S.; Abrahams, Dominique; Carter, Bradford W.; Vagner, Josef; Grobmyer, Stephen R.; Gillies, Robert J.; Morse, David L.

    2014-01-01

    Purpose To develop targeted molecular imaging probes for the non-invasive detection of breast cancer lymph node metastasis. Methods Six cell surface or secreted markers were identified by expression profiling and from the literature as being highly expressed in breast cancer lymph node metastases. Two of these markers were cell surface carbonic anhydrase isozymes (CAIX and/or CAXII) and were validated for protein expression by immunohistochemistry (IHC) of patient tissue samples on a breast cancer tissue microarray containing 47 normal breast tissue samples, 42 ductal carcinoma in situ, 43 invasive ductal carcinomas without metastasis, 46 invasive ductal carcinomas with metastasis and 49 lymph node macrometastases of breast carcinoma. Targeted probes were developed by conjugation of CAIX and CAXII specific monoclonal antibodies (mAbs) to a near-infrared fluorescent dye. Results Together, these two markers were expressed in 100% of the lymph node metastases surveyed. Selectivity of the imaging probes were confirmed by intravenous injection into nude mice bearing mammary fat pad tumors of marker expressing cells, and non-expressing cells or by pre-injection of unlabeled antibody. Imaging of LN metastases showed that peritumorally-injected probes detected nodes harboring metastatic tumor cells. As few as 1,000 cells were detected, as determined by implanting, under ultrasound guidance, a range in number of CAIX and CAXII expressing cells into the axillary LNs. Conclusion These imaging probes have potential for non-invasive staging of breast cancer in the clinic and elimination of unneeded surgery, which is costly and associated with morbidities. PMID:22016510

  19. Up-regulation of METCAM/MUC18 promotes motility, invasion, and tumorigenesis of human breast cancer cells

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    Cai Shao-xi

    2011-03-01

    Full Text Available Abstract Background Conflicting research has identified METCAM/MUC18, an integral membrane cell adhesion molecule (CAM in the Ig-like gene super-family, as both a tumor promoter and a tumor suppressor in the development of breast cancer. To resolve this, we have re-investigated the role of this CAM in the progression of human breast cancer cells. Methods Three breast cancer cell lines were used for the tests: one luminal-like breast cancer cell line, MCF7, which did not express any METCAM/MUC18, and two basal-like breast cancer cell lines, MDA-MB-231 and MDA-MB-468, which expressed moderate levels of the protein. MCF7 cells were transfected with the human METCAM/MUC18 cDNA to obtain G418-resistant clones which expressed the protein and were used for testing effects of human METCAM/MUC18 expression on in vitro motility and invasiveness, and in vitro and in vivo tumorigenesis. Both MDA-MB-231 and MDA-MB-468 cells already expressed METCAM/MUC18. They were directly used for in vitro tests in the presence and absence of an anti-METCAM/MUC18 antibody. Results In MCF7 cells, enforced METCAM/MUC18 expression increased in vitro motility, invasiveness, anchorage-independent colony formation (in vitro tumorigenesis, and in vivo tumorigenesis. In both MDA-MB-231 and MDA-MB-468 cells, the anti-METCAM/MUC18 antibody inhibited both motility and invasiveness. Though both MDA-MB-231 and MDA-MB-468 cells established a disorganized growth in 3D basement membrane culture assay, the introduction of the anti-METCAM/MUC18 antibody completely destroyed their growth in the 3D culture. Conclusion These findings support the notion that human METCAM/MUC18 expression promotes the progression of human breast cancer cells by increasing their motility, invasiveness and tumorigenesis.

  20. Atypical Distant Metastasis of Breast Malignant Phyllodes Tumors: A Case Report and Literature Review

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    Tiphaine de Foucher

    2017-01-01

    Full Text Available Malignant phyllodes tumors (MPT are rare breast neoplasms. Preoperative diagnosis is often challenging due to the unspecific clinical, radiological, and histological characteristics of the tumor. Dissemination pathways are local with chest wall invasion, regional with lymph nodes metastasis, and distant, hematogenous, mostly to the lungs, bones, and brain. Distant metastasis (DM can be synchronous or appear months to years after the diagnosis and initial management. The current report describes the case of a 57-year-old woman presenting with a giant/neglected MPT of the breast, with no DM at initial staging, treated by radical modified mastectomy. Motor disorders due to medullar compression by a paravertebral mass appeared at short follow-up, also treated surgically. The patient died from several DM of rapid evolution. To our knowledge, this is the only case described of MPT with metastases to soft tissue causing medullar compression. We present a literature review on unusual metastatic localizations of MPT.

  1. Atypical Distant Metastasis of Breast Malignant Phyllodes Tumors: A Case Report and Literature Review

    Science.gov (United States)

    de Foucher, Tiphaine; Roussel, Hélène; Hivelin, Mikael; Rossi, Léa; Cornou, Caroline; Bats, Anne-Sophie; Deloménie, Myriam; Lécuru, Fabrice

    2017-01-01

    Malignant phyllodes tumors (MPT) are rare breast neoplasms. Preoperative diagnosis is often challenging due to the unspecific clinical, radiological, and histological characteristics of the tumor. Dissemination pathways are local with chest wall invasion, regional with lymph nodes metastasis, and distant, hematogenous, mostly to the lungs, bones, and brain. Distant metastasis (DM) can be synchronous or appear months to years after the diagnosis and initial management. The current report describes the case of a 57-year-old woman presenting with a giant/neglected MPT of the breast, with no DM at initial staging, treated by radical modified mastectomy. Motor disorders due to medullar compression by a paravertebral mass appeared at short follow-up, also treated surgically. The patient died from several DM of rapid evolution. To our knowledge, this is the only case described of MPT with metastases to soft tissue causing medullar compression. We present a literature review on unusual metastatic localizations of MPT.

  2. [Phyllodes tumor of the breast: clinicopathologic analysis of 22 cases].

    Science.gov (United States)

    Velázquez-Dohorn, Magalie; Gamboa-Domínguez, Armando; Medina-Franco, Heriberto

    2013-01-01

    Phyllodes tumors of the breast are uncommon fibroepithelial neoplasms that have potential for recurrence. They are classified as benign, borderline, and malignant, based on a constellation of histologic characteristics that includes the degree of stromal hypercellularity, cytologic atypia and mitotic activity. To analyze the clinical and pathological features of 22 women treated at a referral center in Mexico City. We performed a retrospective analysis of women with phyllodes tumors of the breast treated at our institution between 1998 and 2011. Age, tumor size, surgical method, stromal cellular atypia, mitotic activity, stromal overgrowth, histological classification and surgical margin status were analyzed to determine their possible association with tumor recurrence. Mean patient age at presentation was 42 years. Ten of them (43.5%) had late menarche. Six patients (27.27%) used hormones. Twenty patients (91%) had tumor detected by self-examination. Mean size of the lesion was 7.4 cm. Most lesions were located in the upper outer quadrant (77.3%) and in the left breast (59.1%). Fourteen patients (63.6%) were treated with conservative surgery. Three patients (13.6%) presented local recurrence, two as benign tumors and one patient with two recurrences, first as benign tumor thereafter as malignant phyllodes tumor at 72 and 108 months respectively. . In our study, surgical positive margin status is the main prognostic factor for recurrence.

  3. Tumor angiogenesis in colorectal cancer, correlation with tumor extension and invasion

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    Javadi P

    2001-09-01

    Full Text Available Tumor angiogenesis shown by Microvessel Count (MVC or Microvessel Density (MVD, is assessed by several studies as prognostic factor in some types of tumors, and also in colorectal carcinoma. This article is payed to correlation between clincopathologic factors and tumor angiogenesis. In this study, immunohistochemical techniques are used for vascular evaluation in specimens from twenty-nine colorectal carcinoma, and stained for Factor VIII-Related Antigen (F8RA by using monoclonal antibody. Uni and multivariate analysis disclosed that total MVC was higher in tumor [76.3±33 (×100=2.5 mm²/field and 29.8±11 (×200=0.785 mm²/field] than in normal tissue [37.7±15.8 (×100 and 17.6±7.8 (×200], (P=0.022, P=0.000009. Microvessel quantification was significantly higher in stage D (115±36.6, ×100 and 26.7±6.4, ×200, P=0.002 and P=0.04. In this study MVD has correlation with vascular invasion (P=0.024, ×100 and P=0.007, ×200, the mean tumor vessel count although was increased with clinicophatologic findings such as age<60 years, male, right colon involvement, infiltrating type, mucinous carcinoma, transmural penetration, grade III, lymphatic and perineural invasion, but was not statistically significant. Lymph node and hematogenous metastasis and size of tumor also, was not important. As a conclusion, MVD was increased in tumor and has shown correlation with metastasis, and vascular invasion. Resulting angiogenesis increase risk of metastasis.

  4. [Effects of MT1-MMP on the in vitro invasiveness of breast cancer cells].

    Science.gov (United States)

    Yao, Guang-yu; Zeng, Mu-sheng; Lin, Peng; Song, Li-bing; Zhang, Xing; He, Jie-hua; Yang, Ming-ting; Rong, Tie-hua

    2006-09-01

    To investigate the effect of membrane type-1 matrix metalloproteinase (MTI-MMP) on the invasive potential of breast cancer cell and analyze its mechanisms. After treatment of breast cancer MDA-MB-453 cell line with concanavalin A ( ConA, 20 microg/ml) for 24 h, MT1-MMP protein was detected in cancer cells by Western analysis and immunocytochemistry. MDA-MB-453 cells were cultured with exogenous latent proMMP-2 and MMP-2 activity was analyzed by gelatin zymography. The invasive potential of the tumor cells was measured with a membrane invasion culture system. Cancer cells of the cell line were divided into four groups: the control group treated by neither reagent, group ConA was only treated by ConA, group MMP-2 was treated only by MMP-2, and group ConA + MMP-2 was treated by both ConA and MMP-2. RESULTS The expression of MTI-MMP protein could be detected in groups ConA and ConA + MMP-2, but nothing was detected in control and group MMP-2. There was only 72 000 precursor form of MMP-2 in group MMP-2 and there were both 72 000 precursor form and 64 000 active enzyme form of MMP-2 in group ConA + MMP-2, but there was no forms of MMP-2 in the other two groups detected by gelatin zymography. The largest amount of cells penetrated through Matrigel was observed in group ConA + MMP-2 than in the other three groups. MTI-MMP can remarkably promote the invasive potential of breast cancer cells mainly through its ability of activating latent proMMP-2 to degrade

  5. Malignant peripheral nerve sheath tumor of the breast: case report

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    Roy Somak

    2007-12-01

    Full Text Available Abstract Background Malignant peripheral nerve sheath tumor is a rare soft tissue sarcoma of ectomesenchymal origin. It is the malignant counterpart of benign soft tissue tumors like neurofibromas and schwannomas and may often follow them. Common sites include deeper soft tissues, usually in the proximity of a nerve trunk. Breast is an extremely rare location of this lesion and presentation as a breast lump in the absence of pain or previous benign neural tumor is even rarer. Case presentation A 38-year-old female presented with complaints of painless, hard breast lump for three months which was clinically suspected to be a ductal carcinoma with inconclusive fine needle aspiration cytology. Histopathology revealed a malignant spindle cell tumor which was confirmed to be malignant peripheral nerve sheath tumor on the basis of immunopositivity for vimentin, neurone specific enolase and S-100. Conclusion To the best of our knowledge only six such case reports have been published in literature. The differential diagnosis of malignant peripheral nerve sheath tumor should be considered by the clinician as well as the pathologists in the work-up of a breast neoplasm as treatment and prognosis of this rare malignancy is different.

  6. Predicting local recurrence following breast-conserving treatment: parenchymal signal enhancement ratio (SER) around the tumor on preoperative MRI.

    Science.gov (United States)

    Kim, Mi Young; Cho, Nariya; Koo, Hye Ryoung; Yun, Bo La; Bae, Min Sun; Chie, Eui Kyu; Moon, Woo Kyung

    2013-09-01

    The level of background parenchymal enhancement around tumor is known to be associated with breast cancer risk. However, there is no study investigating predictive power of parenchymal signal enhancement ratio (SER) around tumor for ipsilateral breast tumor recurrence (IBTR). To investigate whether the breast parenchymal SER around the tumor on preoperative dynamic contrast-enhanced magnetic resonance imaging (MRI) is associated with subsequent IBTR in breast cancer patients who had undergone breast-conserving treatment. Nineteen consecutive women (mean age, 44 years; range, 34-63 years) with breast cancer who developed IBTR following breast-conserving treatment and 114 control women matched for age, as well as T and N stages were included. We compared the clinicopathologic features of the two groups including nuclear grade, histologic grade, hormonal receptor status, human epidermal growth factor receptor-2 (HER-2) status, lymphovascular invasion, negative margin width, use of adjuvant therapy, and parenchymal SER around the tumor on preoperative DCE-MRI. The SER was measured on a slice showing the largest dimension of the tumor. Multivariate conditional logistic regression analysis was used to identify independent factors associated with IBTR. In univariate analysis, ER negativity (odds ratio [OR] = 4.7; P = 0.040), PR negativity (OR = 4.0; P = 0.013), HER-2 positivity (OR = 3.6; P = 0.026), and a parenchymal SER greater than 0.53 (OR = 23.3; P = 0.011) were associated with IBTR. In multivariate analysis, ER negativity (OR = 3.8; P = 0.015) and a parenchymal SER greater than 0.53 (OR = 13.2; P = 0.040) on preoperative MRI were independent factors associated with IBTR. In addition to ER negativity, a higher parenchymal SER on preoperative MRI was an independent factor associated with subsequent IBTR in patients with breast cancer who had undergone breast-conserving treatment.

  7. Predicting local recurrence following breast-conserving treatment: parenchymal signal enhancement ratio (SER) around the tumor on preoperative MRI

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    Kim, Mi Young; Cho, Nariya; Koo, Hye Ryoung; Yun, Bo La; Bae, Min Sun; Moon, Woo Kyung [Dept. of Radiology, Seoul National Univ. Coll. of Medicine, Seoul National Univ. Hospital, Seoul (Korea, Republic of)], e-mail: river7774@gmail.com; Chie, Eui Kyu [Dept. of Radiation Oncology, Seoul National Univ. Coll. of Medicine, Seoul National Univ. Hospital, Seoul (Korea, Republic of)

    2013-09-15

    Background: The level of background parenchymal enhancement around tumor is known to be associated with breast cancer risk. However, there is no study investigating predictive power of parenchymal signal enhancement ratio (SER) around tumor for ipsilateral breast tumor recurrence (IBTR). Purpose: To investigate whether the breast parenchymal SER around the tumor on preoperative dynamic contrast-enhanced magnetic resonance imaging (MRI) is associated with subsequent IBTR in breast cancer patients who had undergone breast-conserving treatment. Material and Methods: Nineteen consecutive women (mean age, 44 years; range, 34-63 years) with breast cancer who developed IBTR following breast-conserving treatment and 114 control women matched for age, as well as T and N stages were included. We compared the clinicopathologic features of the two groups including nuclear grade, histologic grade, hormonal receptor status, human epidermal growth factor receptor-2 (HER-2) status, lymphovascular invasion, negative margin width, use of adjuvant therapy, and parenchymal SER around the tumor on preoperative DCE-MRI. The SER was measured on a slice showing the largest dimension of the tumor. Multivariate conditional logistic regression analysis was used to identify independent factors associated with IBTR. Results: In univariate analysis, ER negativity (odds ratio [OR] = 4.7; P = 0.040), PR negativity (OR = 4.0; P = 0.013), HER-2 positivity (OR = 3.6; P = 0.026), and a parenchymal SER greater than 0.53 (OR = 23.3; P = 0.011) were associated with IBTR. In multivariate analysis, ER negativity (OR = 3.8; P = 0.015) and a parenchymal SER greater than 0.53 (OR = 13.2; P = 0.040) on preoperative MRI were independent factors associated with IBTR. Conclusion: In addition to ER negativity, a higher parenchymal SER on preoperative MRI was an independent factor associated with subsequent IBTR in patients with breast cancer who had undergone breast-conserving treatment.

  8. Enantioselective Effects of o,p'-DDT on Cell Invasion and Adhesion of Breast Cancer Cells: Chirality in Cancer Development.

    Science.gov (United States)

    He, Xiangming; Dong, Xiaowu; Zou, Dehong; Yu, Yang; Fang, Qunying; Zhang, Quan; Zhao, Meirong

    2015-08-18

    The o,p'-dichlorodiphenyltrichloroethane (DDT) with a chiral center possesses enantioselective estrogenic activity, in which R-(-)-o,p'-DDT exerts a more potent estrogenic effect than S-(+)-o,p'-DDT. Although concern regarding DDT exposure and breast cancer has increased in recent decades, the mode of enantioselective action of o,p'-DDT in breast cancer development is still unknown. Herein, we conducted a systematic study of the effect of o,p'-DDT on stereoselective breast tumor cell progression in a widely used in vitro breast tumor cell model, MCF-7 cells. We demonstrated that R-(-)-o,p'-DDT promoted more cancer cell invasion mediated by the human estrogen receptor (ER) by inducing invasion-promoted genes (matrix metalloproteinase-2 and -9 and human telomerase reverse transcriptase) and inhibiting invasion-inhibited genes (tissue inhibitor of metalloproteinase-1 and -4). Molecular docking verified that the binding affinity between R-(-)-o,p'-DDT and human ER was stronger than that of S-(+)-o,p'-DDT. The enantioselective-induced decrease in cell-to-cell adhesion may involve the downregulation of adhesion-promoted genes (E-cadherin and β-catenin). For the first time, these results reveal that estrogenic-like chiral compounds are of significant concern in the progression of human cancers and that human health risk assessment of chiral chemicals should consider enantioselectivity.

  9. Analysis by MRI of residual tumor after radiofrequency ablation for early stage breast cancer.

    Science.gov (United States)

    Vilar, Vanessa Sales; Goldman, Suzan Menasce; Ricci, Marcos Desidério; Pincerato, Katia; Oliveira, Helio; Abud, Thiago Giansante; Ajzen, Sergio; Baracat, Edmund Chada; Szejnfeld, Jacob

    2012-03-01

    The objective of our study was to evaluate the effectiveness of MRI in the detection of possible residual lesions after radiofrequency ablation (RFA) in the treatment of breast cancer. We prospectively evaluated 14 patients who had undergone ultrasound-guided core biopsies diagnostic of invasive ductal carcinoma (IDC; range of diameters, 1.0-3.0 cm) and then ultrasound-guided percutaneous RFA with sentinel node biopsy as the primary treatment. Breast MRI was performed 1 week before RFA to evaluate tumor extension and again 3 weeks after RFA to verify the presence of possible residual lesions. Conventional surgical resection of the tumors was performed 1 week after RFA. The MRI findings were compared with histopathologic analyses to confirm the presence or absence of residual tumor. There was no residual enhancement in seven lesions on the postablation breast MRI scans. These findings were confirmed by negative histopathologic findings in the surgical specimens. The MRI scans of five patients showed small areas of irregular enhancement that corresponded to residual lesions. In the two remaining patients, we observed enhancement of almost the entire lesion, indicating that RFA had failed. Breast MRI is effective in detecting residual lesions after RFA in patients with IDC.

  10. Total RNA Sequencing Analysis of DCIS Progressing to Invasive Breast Cancer

    Science.gov (United States)

    2016-09-01

    epigenetic alterations of pre-invasive DCIS that did or did not progress to invasive breast cancer, with an in-depth...NIH- funded study of genetic and epigenetic alterations of pre-invasive DCIS that either progressed to invasive breast cancer IBC (cases) or had no...Hill, NC 27599 8. Special Reporting Requirements N/A 9. Appendices 19 References 1. R-Core-Team: R: A language and environment

  11. Assessment of HER-2 status in invasive breast cancer in Brazil.

    Science.gov (United States)

    Arias, Victor Eduardo Arrua; Gobbi, Helenice; Ioshii, Sérgio Ossamu; Scapulatempo, Cristovam; Paz, Alexandre Rolim da; Silva, Vinicius Duval da; Uchôa, Diego; Zettler, Claudio; Soares, Fernando Augusto

    2017-07-01

    To characterize the frequency of HER-2-positive breast cancer in Brazil. In this prospective observational study, we first ascertained the HER-2 status of invasive breast cancer specimens by automated immunohistochemistry (IHC). For specimens classified as 2+ by IHC, we performed in situ hybridization (ISH). From February, 2011 to December, 2012, 1,495 breast specimens were registered, and 1,310 samples collected at 24 centers were analyzed. Median patient age was 54 years, and the majority of samples were obtained from segmental (46.9%) or radical mastectomy (34.4%). The predominant histological type was invasive breast carcinoma of no special type (85%), 64.3% had tubule formation (grade 3), and estrogen/progesterone receptors (ER/PR) were positive in 77.4/67.8% of the specimens analyzed, respectively. Using IHC, we found a negative HER-2 status (0 or 1+) in 72.2% of specimens, and 3+ in 18.5%; the 9.3% scored as 2+ were further analyzed by ISH, of which 15.7% were positive (thus, 20.0% of samples were HER-2- -positive by either method). We found no association between HER-2 scores and menopausal status or histological type. Tumors classified as 3+ came from younger patients, and had higher histological grade and less frequent expression of ER/PR. In the North region of Brazil, 34.7% of samples were 3+, with lower frequencies in the other four regions of the country. Our findings provide estimates for the frequency of HER-2 positivity in Brazil and raise the hypothesis that biological differences may underlie the different distribution of breast-cancer phenotypes among different Brazilian regions.

  12. Heat shock protein 90β stabilizes focal adhesion kinase and enhances cell migration and invasion in breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Xiong, Xiangyang [Center for Experimental Medicine, The First Affiliated Hospital of Nanchang University, 17 Yongwai Street, Donghu District, Nanchang, Jiangxi 330006 (China); Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Nanchang University, Nanchang, Jiangxi 330006 (China); State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, Jiangxi 330047 (China); Wang, Yao [Center for Experimental Medicine, The First Affiliated Hospital of Nanchang University, 17 Yongwai Street, Donghu District, Nanchang, Jiangxi 330006 (China); Liu, Chengmei [State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, Jiangxi 330047 (China); Lu, Quqin [Department of Biostatistics and Epidemiology, School of Public Health, Nanchang University, Nanchang, Jiangxi 330006 (China); Liu, Tao [Center for Experimental Medicine, The First Affiliated Hospital of Nanchang University, 17 Yongwai Street, Donghu District, Nanchang, Jiangxi 330006 (China); Chen, Guoan [Department of Hematology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006 (China); Rao, Hai [Department of Molecular Medicine, University of Texas Health Science Center, San Antonio, TX 78229 (United States); Luo, Shiwen, E-mail: shiwenluo@ncu.edu.cn [Center for Experimental Medicine, The First Affiliated Hospital of Nanchang University, 17 Yongwai Street, Donghu District, Nanchang, Jiangxi 330006 (China)

    2014-08-01

    Focal adhesion kinase (FAK) acts as a regulator of cellular signaling and may promote cell spreading, motility, invasion and survival in malignancy. Elevated expression and activity of FAK frequently correlate with tumor cell metastasis and poor prognosis in breast cancer. However, the mechanisms by which the turnover of FAK is regulated remain elusive. Here we report that heat shock protein 90β (HSP90β) interacts with FAK and the middle domain (amino acids 233–620) of HSP90β is mainly responsible for this interaction. Furthermore, we found that HSP90β regulates FAK stability since HSP90β inhibitor 17-AAG triggers FAK ubiquitylation and subsequent proteasome-dependent degradation. Moreover, disrupted FAK-HSP90β interaction induced by 17-AAG contributes to attenuation of tumor cell growth, migration, and invasion. Together, our results reveal how HSP90β regulates FAK stability and identifies a potential therapeutic strategy to breast cancer. - Highlights: • HSP90β protects FAK from degradation by the ubiquitin-proteasome pathway. • Inhibition of HSP90β or FAK attenuates tumorigenesis of breast cancer cells. • Genetic repression of HSP90β or FAK inhibits tumor cell migration and proliferation. • Inhibition of HSP90β or FAK interferes cell invasion and cytoskeleton.

  13. Radiation therapy and chemotherapy after breast conserving surgery for invasive breast cancer: an intermediate result

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Seok Ho; Lee, Kyu Chan; Choi, Jin Ho; Lee, Young Don; Park, Heoung Kyu; Kim, Hyun Young; Park, Se Hoon [Gachon Medical School, Incheon (Korea, Republic of)

    2007-03-15

    Breast conserving surgery (BCS) followed by chemotherapy (CT{sub x}.) and radiation therapy (RT) is widely performed for the treatment of early breast cancer. This retrospective study was undertaken to evaluate our interim results in terms of failure patterns, survival and relative risk factors. From January 1999 through December 2003, 129 patients diagnosed with invasive breast cancer and treated with BCS followed by RT were subject to retrospective review. The median age of the patients was 45 years (age distribution, 27 {approx} 76 years). The proportions of patients according to their tumor, nodes, and metastases (TNM) stage were 65 (50.4%) in stage I, 41 (31.7%) in stage IIa, 13 (10.1%) in stage IIb, 9 (7.0%) in stage III, and 1 patient (0.8%) in stage IIIc. For 32 patients (24.8%), axillary node metastasis was found after dissection, BCS consisted of quadrantectomy in 115 patients (89.1%) and lumpectomy in 14 patients (10.6%). Axillary node dissection at axillary level I and II was performed for 120 patients (93%). For 7 patients (5.4%), only sentinel node dissection was performed with BCS. For 2 patients (1.6%) axillary dissection of any type was not performed. Postoperative RT was given with 6 MV X-rays. A tumor dose of 50.4 Gy was delivered to the entire breast area using a tangential field with a wedge compensator. An additional dose of 9 {approx} 16 Gy was given to the primary tumor bed areas with electron beams. In 30 patients (23.3%), RT was delivered to the supraclavicular node. Most patients had adjuvant CT{sub x}. with 4 {approx} 6 cycles of CMF (cyclophosphamide, methotrexate, 5-fluorouracil) regimens. The median follow-up period was 50 months (range: 17 {approx} 93 months). The actuarial 5 year survival rate (5Y-OSR) was 96.9%, and the 5 year disease free survival rate (5Y-DFSR) was 93.7%. Local recurrences were noted in 2 patients (true: 2, regional node: 1) as the first sign of recurrence at a mean time of 29.3 months after surgery. Five

  14. Serum total PSA and free PSA in breast tumors

    OpenAIRE

    Dash, Prakruti; Pati, Sanghamitra; Mangaraj, Manaswini; Sahu, Pratima Kumari; Mohapatra, Prakash Chandra

    2011-01-01

    Now a days measurement of molecular forms of PSA has gained importance in clinical practice. Several studies have demonstrated the production of PSA in female tissues, such as breast. The present piece of work has been undertaken with an objective to estimate the relative proportion of the molecular forms of PSA in serum along with serum testosterone in benign and malignant breast tumor cases and to analyze their association with the severity of the disease process 34 malignant and 26 benign ...

  15. Occult Invasive Lobular Carcinoma of Breast Detected by Stomach Metastasis: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    KIm, So Jung; Jung, Hae Kyoung; Ko, Kyung Hee; Yoon, Jung Hyun [Dept. of Radiology, Bundang CHA general Hospital, CHA University College of Medicine, Seongnam (Korea, Republic of)

    2012-02-15

    Gastric metastasis from primary breast cancer is a rare phenomenon that is more prevalent in the invasive lobular type of breast cancer. We describe a very rare case of occult invasive lobular cancer of the breast detected by the initial presentation of gastric metastasis in a patient without a history of breast cancer. A 18F-fluorodeoxyglucose positron-emission tomography/computed tomography (FDG PET/CT) which showed increased FDG uptake in the stomach, abdominal mesentery and the right breast, and played pivotal roles in the detection of occult primary breast cancer and a diagnosis of gastric metastasis as an ancillary method for obtaining histological results and immunohistochemical stains.

  16. Elemene inhibits the migration and invasion of 4T1 murine breast cancer cells via heparanase.

    Science.gov (United States)

    Zhang, Yi; Sun, Xu; Nan, Nan; Cao, Ke-Xin; Ma, Cong; Yang, Guo-Wang; Yu, Ming-Wei; Yang, Lin; Li, Jin-Ping; Wang, Xiao-Min; Zhang, Gan-Lin

    2017-07-01

    Elemene (ELE), a natural plant drug extracted from Curcumae Rhizoma, has been widely used for cancer treatment in China for more than 20 years. Although it is reported to be a broad‑spectrum anticancer drug, the mechanism underlying the action of ELE in the treatment of breast cancer remains to be fully elucidated. Heparanase, a mammalian endo‑D‑glucuronidase, is involved in degradation of the extracellular matrix (ECM), and thus promotes tumor progression and metastasis. The downregulation of heparanase can effectively reduce tumor malignant behaviors. In the present study, the inhibitory effects of ELE were evaluated in breast cancer cells using a Cell Counting kit 8 assay. The migratory and invasive capabilities of cancer cells were investigated using a wound healing assay, real‑time cell analysis and a Transwell assay. In addition, western blot analysis was used to assess alterations in the expression levels of key proteins. The present results confirmed the antiproliferative and antimetastatic effects of ELE, using low‑molecular weight heparin (LMWH) as a positive control. In addition, ELE was demonstrated to downregulate the expression of heparanase, and decrease the phosphorylation of extracellular signal‑regulated kinase and AKT. These findings suggested that ELE may be a promising agent targeting heparanase in the treatment of breast cancer.

  17. Tumor size, depth of invasion, and grading of the invasive tumor front are the main prognostic factors in early squamous cell cervical carcinoma.

    Science.gov (United States)

    Kristensen, G B; Abeler, V M; Risberg, B; Trop, C; Bryne, M

    1999-08-01

    The objective of this study was to evaluate the prognostic significance of clinical and histopathologic factors, including a new grading system focusing on the invasive tumor front. A retrospective analysis of 125 surgically treated patients with squamous cell cervical carcinoma FIGO stage IB was conducted. For each tumor, the degree of keratinization, nuclear polymorphism, pattern of invasion, and degree of lymphoid infiltration at the invasive tumor front were graded and given scores between 1 and 4. Clinical tumor size, depth of invasion, and grading of the invasive front had prognostic significance in multivariate analysis, while lymph vascular space involvement, lymph node status, and grade of differentiation did not. Based on clinical tumor size, depth of invasion, and grading of the invasive tumor front, patients could be separated into three groups: One group with minimal risk of recurrence (5-year disease-free survival (DFS) of 100%) consisting of 24% of the patients, an intermediate group with a fairly low risk of recurrence (5-year DFS of about 92%), and a high risk group with a 5-year DFS of 45%. This latter group contained 26% of the patients with 78% of all relapses occurring in the total group of patients. The invasive tumor front grading was reliably reproducible, with inter- and intraobserver agreement of 79 to 87% and kappa values of 0.47 to 0.66. Clinical tumor size, depth of invasion, and grading of the invasive tumor front were the main predictors of prognosis in patients with stage IB squamous cell cancer of the cervix. Copyright 1999 Academic Press.

  18. 3-D visualization and non-linear tissue classification of breast tumors using ultrasound elastography in vivo.

    Science.gov (United States)

    Sayed, Ahmed; Layne, Ginger; Abraham, Jame; Mukdadi, Osama M

    2014-07-01

    The goal of the study described here was to introduce new methods for the classification and visualization of human breast tumors using 3-D ultrasound elastography. A tumor's type, shape and size are key features that can help the physician to decide the sort and extent of necessary treatment. In this work, tumor type, being either benign or malignant, was classified non-invasively for nine volunteer patients. The classification was based on estimating four parameters that reflect the tumor's non-linear biomechanical behavior, under multi-compression levels. Tumor prognosis using non-linear elastography was confirmed with biopsy as a gold standard. Three tissue classification parameters were found to be statistically significant with a p-value linear parameter was highly significant, having a p-value < 0.001. Furthermore, each breast tumor's shape and size were estimated in vivo using 3-D elastography, and were enhanced using interactive segmentation. Segmentation with level sets was used to isolate the stiff tumor from the surrounding soft tissue. Segmentation also provided a reliable means to estimate tumors volumes. Four volumetric strains were investigated: the traditional normal axial strain, the first principal strain, von Mises strain and maximum shear strain. It was noted that these strains can provide varying degrees of boundary enhancement to the stiff tumor in the constructed elastograms. The enhanced boundary improved the performance of the segmentation process. In summary, the proposed methods can be employed as a 3-D non-invasive tool for characterization of breast tumors, and may provide early prognosis with minimal pain, as well as diminish the risk of late-stage breast cancer. Copyright © 2014 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

  19. Interventional MRI of the breast: minimally invasive therapy

    Energy Technology Data Exchange (ETDEWEB)

    Hall-Craggs, M.A. [MR Unit, Middlesex Hospital, London (United Kingdom)

    2000-01-01

    In recent years a variety of minimally invasive therapies have been applied to the treatment of breast lesions. These therapies include thermal treatments (interstitial laser coagulation, focused ultrasound, radiofrequency and cryotherapy), percutaneous excision, and interstitial radiotherapy. Magnetic resonance has been used in these treatments to visualize lesions before, during and after therapy and to guide interventions. ''Temperature-sensitive'' sequences have shown changes with thermal ablation which broadly correlate with areas of tumour necrosis. Consequently, MR has the potential to monitor treatment at the time of therapy. To date, experience in the treatment of breast cancer has been restricted to small studies. Large controlled studies are required to validate the efficacy and safety of these therapies in malignant disease. (orig.)

  20. [Metastatic cervical fasciitis revealing invasive lobular breast carcinoma].

    Science.gov (United States)

    Munoz, J; Garcia, C; Joujoux, J-M; Dandurand, M; Meunier, L; Stoebner, P-E

    2015-02-01

    We describe the case of a 71-year-old woman presenting cervical metastatic fasciitis with invasive lobular carcinoma (ILC) of the breast. The patient consulted for a deep and painless skin infiltration of the neck associated with dysphagia and restricted cervical mobility. Skin and muscle biopsies were normal. Muscle fascia biopsy showed a linear infiltration of metastatic cells in "single file", revealing ILC of the right breast. ILCs have a particular metastatic pattern. They can permeate through tissue planes, infiltrate solid organs and spread on serous membranes in an insidious fashion. Our case shows that ILC can metastasise into muscular fascia, causing "fasciitis-like" symptoms. Dermatologists should be aware of this particular pattern of dissemination. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  1. Aspirin blocks growth of breast tumor cells and tumor-initiating cells and induces reprogramming factors of mesenchymal to epithelial transition.

    Science.gov (United States)

    Maity, Gargi; De, Archana; Das, Amlan; Banerjee, Snigdha; Sarkar, Sandipto; Banerjee, Sushanta K

    2015-07-01

    Acetylsalicylic acid (ASA), also known as aspirin, a classic, nonsteroidal, anti-inflammatory drug (NSAID), is widely used to relieve minor aches and pains and to reduce fever. Epidemiological studies and other experimental studies suggest that ASA use reduces the risk of different cancers including breast cancer (BC) and may be used as a chemopreventive agent against BC and other cancers. These studies have raised the tempting possibility that ASA could serve as a preventive medicine for BC. However, lack of in-depth knowledge of the mechanism of action of ASA reshapes the debate of risk and benefit of using ASA in prevention of BC. Our studies, using in vitro and in vivo tumor xenograft models, show a strong beneficial effect of ASA in the prevention of breast carcinogenesis. We find that ASA not only prevents breast tumor cell growth in vitro and tumor growth in nude mice xenograft model through the induction of apoptosis, but also significantly reduces the self-renewal capacity and growth of breast tumor-initiating cells (BTICs)/breast cancer stem cells (BCSCs) and delays the formation of a palpable tumor. Moreover, ASA regulates other pathophysiological events in breast carcinogenesis, such as reprogramming the mesenchymal to epithelial transition (MET) and delaying in vitro migration in BC cells. The tumor growth-inhibitory and reprogramming roles of ASA could be mediated through inhibition of TGF-β/SMAD4 signaling pathway that is associated with growth, motility, invasion, and metastasis in advanced BCs. Collectively, ASA has a therapeutic or preventive potential by attacking possible target such as TGF-β in breast carcinogenesis.

  2. Effect of Depleting Tumor-Associated Macrophages on Breast Cancer Growth and Response to Chemotherapy

    National Research Council Canada - National Science Library

    Tsan, Min-Fu; Gao, Baochong

    2005-01-01

    Tumor-associated macrophages may comprise up to 50% of the tumor mass in breast cancer and are capable of producing estrogen and angiogenic cytokines that regulate the growth and angiogenesis of breast cancer...

  3. The PDZ protein TIP-1 facilitates cell migration and pulmonary metastasis of human invasive breast cancer cells in athymic mice.

    Science.gov (United States)

    Han, Miaojun; Wang, Hailun; Zhang, Hua-Tang; Han, Zhaozhong

    2012-05-25

    Tax-interacting protein 1 (TIP-1, also known as Tax1bp3) inhibited proliferation of colon cancer cells through antagonizing the transcriptional activity of beta-catenin. However, in this study, elevated TIP-1 expression levels were detected in human invasive breast cancers. Studies with two human invasive breast cancer cell lines indicated that RNAi-mediated TIP-1 knockdown suppressed the cell adhesion, proliferation, migration and invasion in vitro, and inhibited tumor growth in mammary fat pads and pulmonary metastasis in athymic mice. Biochemical studies showed that TIP-1 knockdown had moderate and differential effects on the beta-catenin-regulated gene expression, but remarkably down regulated the genes for cell adhesion and motility in breast cancer cells. The decreased expression of integrins and paxillin was accompanied with reduced cell adhesion and focal adhesion formation on fibronectin-coated surface. In conclusion, this study revealed a novel oncogenic function of TIP-1 suggesting that TIP-1 holds potential as a prognostic biomarker and a therapeutic target in the treatment of human invasive breast cancers. Copyright © 2012 Elsevier Inc. All rights reserved.

  4. Enhancing Tumor Detection in IR-UWB Breast Cancer System

    Science.gov (United States)

    Ghoname, Reda; Elmahdy, Abd Elmonem; Zekry, Abd Elhalim

    2017-01-01

    An ultra-wideband (UWB) microwave system for breast cancer detection is presented. The proposed system includes monocycle pulse generator, antipodal Vivaldi antenna, breast model, and calibration algorithm for tumor detection. Firstly, our pulse generator employs transmission gate in glitch generator to achieve several advantages such as low power consumption and low ringing level. Secondly, the antipodal Vivaldi antenna is designed assuming FR4 dielectric substrate material, and developed antenna element (80 × 80 mm2) features a −10 dB return loss and bandwidth ranges from 2.3 GHz to more than 11 GHz. Thirdly, the phantom breast can be modeled as a layer of skin, fat, and then tumor is inserted in this layer. Finally, subtract and add algorithm (SAD) is used as a calibration algorithm in tumor detection system. The proposed system suggested that horizontal antenna position with 90° between transmitting and receiving antennas is localized as a suitable antenna position with different rotating location and a 0.5 cm near to phantom. The mean advantages of this localization and tracking position around breast is a high received power signal approximately around mv as a higher recognized signal in tumor detection. Using our proposed system we can detect tumor in 5 mm diameter. PMID:28421208

  5. Enhancing Tumor Detection in IR-UWB Breast Cancer System

    Directory of Open Access Journals (Sweden)

    Sara Fouad

    2017-01-01

    Full Text Available An ultra-wideband (UWB microwave system for breast cancer detection is presented. The proposed system includes monocycle pulse generator, antipodal Vivaldi antenna, breast model, and calibration algorithm for tumor detection. Firstly, our pulse generator employs transmission gate in glitch generator to achieve several advantages such as low power consumption and low ringing level. Secondly, the antipodal Vivaldi antenna is designed assuming FR4 dielectric substrate material, and developed antenna element (80×80 mm2 features a −10 dB return loss and bandwidth ranges from 2.3 GHz to more than 11 GHz. Thirdly, the phantom breast can be modeled as a layer of skin, fat, and then tumor is inserted in this layer. Finally, subtract and add algorithm (SAD is used as a calibration algorithm in tumor detection system. The proposed system suggested that horizontal antenna position with 90° between transmitting and receiving antennas is localized as a suitable antenna position with different rotating location and a 0.5 cm near to phantom. The mean advantages of this localization and tracking position around breast is a high received power signal approximately around mv as a higher recognized signal in tumor detection. Using our proposed system we can detect tumor in 5 mm diameter.

  6. Glutathione Transferase GSTπ In Breast Tumors Evaluated By Three Techniques

    Directory of Open Access Journals (Sweden)

    Rafael Molina

    1993-01-01

    Full Text Available The glutathione transferases are involved in intracellular detoxification reactions. One of these, GSTπ, is elevated in some breast cancer cells, particularly cells selected for resistance to anticancer agents. We evaluated GSTπ expression in 60 human breast tumors by three techniques, immunohistochemistry, Northern hybridization, and Western blot analysis. There was a significant positive correlation between the three methods, with complete concordance seen in 64% of the tumors. There was strong, inverse relationship between GSTπ expression and steroid receptor status with all of the techniques utili zed. [n addition, there was a trend toward higher GSTπ expression in poorly differentiated tumors, but no correlation was found between tumor GSTπ content and DNA ploidy or %S-phase. GSTπ expression was also detected in adjacent benign breast tissue as well as infiltrating lymphocytes; this expression may contribute to GSTπ measurements using either Northern hybridization or Western blot analysis. These re sults suggest that immunohistochemistry is the method of choice for measuring GSTπ in breast tumors.

  7. Tumor thickness and histological features as predictors of invasive foci within preoperatively diagnosed ductal carcinoma in situ.

    Science.gov (United States)

    Mori, Kiyoshi; Takeda, Masashi; Kodama, Yoshinori; Kiyokawa, Hiroki; Yasojima, Hiroyuki; Mizutani, Makiko; Otani, Yoko; Morikawa, Nozomi; Masuda, Norikazu; Mano, Masayuki

    2017-06-01

    Small invasion into ductal carcinoma in situ (DCIS) can easily be overlooked in resected breast specimens. To disclose useful markers predictive of invasive foci within preoperatively diagnosed DCIS lesions, a retrospective histopathological comparison was made between postoperatively diagnosed invasive ductal carcinoma with a predominant intraductal component (IDCPIC) (n=43) and pure DCIS (n=82). Through a multivariate logistic regression analysis model, 5 variables (DCIS grade, "tumor thickness," extent of retraction cleft, presence of lymph node metastasis, and HER2 score) were found to be significantly associated with the presence of invasive foci within DCIS; with a cutoff point of 0.315, sensitivity, specificity, positive predictive value, and negative predictive value were 0.93, 0.77, 0.68, and 0.95, respectively. No statistically significant difference was observed in recurrence-free survival between IDCPIC and pure DCIS, whereas the IDCPIC curve showed a slightly earlier decline than the DCIS one. In general, preoperative detection of lymph node metastasis in DCIS patients is elusive because of the extremely tiny metastatic size in most cases; thus, a 4-variable model, without lymph node metastasis, would be the actual working model. Furthermore, tumor "thickness" was found to be the most significant parameter predictive of invasive foci within DCIS. Although IDCPIC and pure DCIS showed similar recurrence-free survival curves, prediction of invasive foci within DCIS necessitates postoperative pathological analysis of surgically resected lesions. Copyright © 2017 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    2016-12-01

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

  9. High tumor budding count is associated with adverse clinicopathologic features and poor prognosis in breast carcinoma.

    Science.gov (United States)

    Li, Xiaoxian; Wei, Bo; Sonmez, Ceyda; Li, Zaibo; Peng, Limin

    2017-08-01

    This study is to address the significance of tumor budding (TB) in breast carcinoma. Totally 244 estrogen receptor-positive (ER+)/HER2-negative (HER2-) and 131 triple-negative breast carcinoma (TNBC) diagnosed from 2004 to 2014 were analyzed. TB (cluster of up to 5 tumor cells at the invasive front) was evaluated using five 200× high-power fields (HPF) at the hotspot. The highest TB (H-TB) in 1 HPF and average TB (A-TB) in 5 HPFs were correlated with lymph node and distant metastasis, lymphovascular invasion (LVI), local recurrence, overall survival (OS), and disease-free survival (DFS). In ER+/HER2- cancer, H-TB and A-TB were significantly associated with distant metastasis. In TNBC, H-TB was associated with distant metastasis by univariate but not multivariate analysis; H-TB and A-TB were associated with LVI and worse OS (all P < .05). TB is associated with poor prognosis in ER+/HER2- and TNBC cancer. Evaluation of H-TB may be sufficient in breast carcinoma. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Simulation study of an X-ray diffraction system for breast tumor detection

    Science.gov (United States)

    Marticke, F.; Montémont, G.; Paulus, C.; Michel, O.; Mars, J. I.; Verger, L.

    2017-09-01

    X-ray diffraction (XRD) is a powerful technique used to determine the molecular structure of biological tissues. In breast tissues for example, the scattering signatures of dense fibroglandular tissue and carcinoma have been shown to be significantly different. In this study, XRD was used as a second control level when conventional mammography results were unclear, for instance because of overly high breast density. A system optimized for this issue, called multifocal XRD, was developed combining energy dispersive spectral information at different scattering angles. This system allows depth-imaging in one go but needs an x,y-direction scan to image the region conventional mammography identified as suspect. The scan-time for about 10 cm3 with an incident flux of about 4.8·107 photons per second would be around 2 s. For this study, breast phantoms with and without cancerous nodule were simulated to assess the separation power of the method and to determine the radiation dose required to obtain nearly ideal separation. For tumors situated in the center of the breast, the required dose was only about 0.3 mGy, even for breasts with high density. The tumor position was shown to have a low impact on detectability provided it remained in a zone where the system was sufficiently sensitive. The influence of incident spectrum maximum energy was also studied. The required dose remained very low with any of the incident spectra tested. Finally, an image slice was reconstructed in the x-direction and showed that the system can detect the presence of a small tumor (4 mm). Hence, XRD is a very promising tool to reduce the number of unnecessary invasive breast biopsies.

  11. Postoperative CMF Does Not Ameliorate Poor Outcomes in Women With Residual Invasive Breast Cancer After Neoadjuvant Epirubicin/Docetaxel Chemotherapy.

    Science.gov (United States)

    Promberger, Regina; Dubsky, Peter; Mittlböck, Martina; Ott, Johannes; Singer, Christian; Seemann, Rudolf; Exner, Ruth; Panhofer, Peter; Steger, Günther; Bergen, Elisabeth; Gnant, Michael; Jakesz, Raimund; Bago-Horvath, Zsuzsanna; Rudas, Margaretha; Bartsch, Rupert

    2015-12-01

    Neoadjuvant chemotherapy (NACT) is an accepted treatment approach in early-stage breast cancer. In contrast, the potential role of postneoadjuvant chemotherapy after taxane-containing NACT remains unclear. The aim of this study was to evaluate postneoadjuvant chemotherapy and further prognostic factors that predict outcome in women without pathologic complete remission (pCR). A total of 377 patients with breast cancer who received preoperative chemotherapy were included in this retrospective study. Patients without standard NACT (6 cycles of epirubicin with docetaxel) or primary metastatic breast cancer and locally advanced, inoperable cancer were excluded from further analysis (n = 186). This resulted in a study population of 191 women (30 [15.7%] with pCR; 161 [84.3%] without pCR). Major outcome parameters were event-free survival (EFS) and overall survival (OS). The following parameters were tested for their prognostic role: postneoadjuvant chemotherapy, patient age, breast cancer subtype (luminal/HER2-negative tumors, HER2-positive tumors, and triple-negative tumors), histological grade, pCR, residual lymph node invasion, and residual invasive tumor size. At a median follow-up of 54 months, 51 disease relapses (26.7%) and 21 deaths (11%) were observed. In a comparison of patients with pCR with those without, no significant differences in EFS or OS were observed. Postneoadjuvant chemotherapy was significantly associated with shorter OS in patients without pCR. In this population, which included a high percentage of patients with luminal cancers, pCR did not predict for improved OS. Postneoadjuvant chemotherapy showed no discernible benefit even in subgroups with aggressive tumor biology or significant remaining tumor burden. The use of such treatment should therefore be discouraged outside of clinical trials. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Background parenchymal enhancement in breast MRIs of breast cancer patients: Impact on tumor size estimation

    Energy Technology Data Exchange (ETDEWEB)

    Baek, Ji Eun [Department of Radiology, Seoul St. Mary' s Hospital, College of Medicine, The Catholic University of Korea (Korea, Republic of); Kim, Sung Hun, E-mail: rad-ksh@catholic.ac.kr [Department of Radiology, Seoul St. Mary' s Hospital, College of Medicine, The Catholic University of Korea (Korea, Republic of); Lee, Ah Won [Department of Hospital Pathology, Seoul St. Mary' s Hospital, College of Medicine, The Catholic University of Korea (Korea, Republic of)

    2014-08-15

    Objective: To evaluate whether the degree of background parenchymal enhancement affects the accuracy of tumor size estimation based on breast MRI. Methods: Three hundred and twenty-two patients who had known breast cancer and underwent breast MRIs were recruited in our study. The total number of breast cancer cases was 339. All images were assessed retrospectively for the level of background parenchymal enhancement based on the BI-RADS criteria. Maximal lesion diameters were measured on the MRIs, and tumor types (mass vs. non-mass) were assessed. Tumor size differences between the MRI-based estimates and estimates based on pathological examinations were analyzed. The relationship between accuracy and tumor types and clinicopathologic features were also evaluated. Results: The cases included minimal (47.5%), mild (28.9%), moderate (12.4%) and marked background parenchymal enhancement (11.2%). The tumors of patients with minimal or mild background parenchymal enhancement were more accurately estimated than those of patients with moderate or marked enhancement (72.1% vs. 56.8%; p = 0.003). The tumors of women with mass type lesions were significantly more accurately estimated than those of the women with non-mass type lesions (81.6% vs. 28.6%; p < 0.001). The tumor of women negative for HER2 was more accurately estimated than those of women positive for HER2 (72.2% vs. 51.6%; p = 0.047). Conclusion: Moderate and marked background parenchymal enhancement is related to the inaccurate estimation of tumor size based on MRI. Non-mass type breast cancer and HER2-positive breast cancer are other factors that may cause inaccurate assessment of tumor size.

  13. ?Ruptured? malignant phyllodes tumor of the breast: a case report

    OpenAIRE

    Ditsatham, Chagkrit; Somwangprasert, Areewan; Watcharachan, Kirati; Wongmaneerung, Phanchaporn

    2016-01-01

    Chagkrit Ditsatham, Areewan Somwangprasert, Kirati Watcharachan, Phanchaporn WongmaneerungDivision of Head, Neck and Breast, Department of Surgery, Chiang Mai University, Chiang Mai, ThailandAbstract: Phyllodes tumor or cystosarcoma phyllodes is a rare disease and is usually seen in middle-aged patients. Ruptured phyllodes tumor is a very rare condition. Our study reports patient presentation, diagnosis method, and treatment of an unusual case. A 58-year-old premenopausal female was diagnosed...

  14. One-Carbon Metabolism and Methylation in Breast Tumors

    Science.gov (United States)

    2007-06-01

    149 TABLE A.34 Odds ratios and 95% CI for risk of p16 methylation tumor by MTHFR A1298C genotype, WNYDS *adjusted for age, education...AD_________________ Award Number: DAMD17-03-1-0344 TITLE: One – Carbon Metabolism and Methylation ...CONTRACT NUMBER One – Carbon Metabolism and Methylation in Breast Tumors 5b. GRANT NUMBER DAMD17-03-1-0344 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR

  15. Gene Promoter Hypermethylation in Tumors and Plasma of Breast Cancer Patients

    Science.gov (United States)

    Shim, Young Ran; Choi, Joon Hyuk; Kim, Mi Jin; Gabrielson, Edward; Lee, Soo Jung; Hwang, Tae Yoon; Shin, Sei One

    2005-01-01

    Purpose To measure the hypermethylation of four genes in primary tumors and paired plasma samples to determine the feasibility of gene promoter hypermethylation markers for detecting breast cancer in the plasma. Materials and Methods DNA was extracted from the tumor tissues and peripheral blood plasma of 34 patients with invasive breast cancer, and the samples examined for aberrant hypermethylation in cyclin D2, retinoic acid receptor β (RARβ), twist and high in normal-1 (HIN-1) genes using methylation-specific PCR (MSP), and the results correlated with the clinicopathological parameters. Results Promoter hypermethylation was detected at high frequency in the primary tumors for cyclin D2 (53%), RARβ (56%), twist (41%) and HIN-1 (77%). Thirty-three of the 34 (97%) primary tumors displayed promoter hypermethylation in at least one of the genes examined. The corresponding plasma samples showed hyperme thylation of the same genes, although at lower frequencies (6% for cyclin D2, 16% for RARβ, 36% for twist, and 54% for HIN-1). Overall, 22 of the 33 (67%) primary tumors with hypermethylation of at least one of the four genes also had abnormally hypermethylated DNA in their matched plasma samples. No significant relationship was recognized between any of the clinical or pathological parameters (tumor size, axillary lymph node metastasis, stage, or Ki-67 labeling index) with the frequency of hypermethylated DNA in the primary tumor or plasma. Conclusion The detection of aberrant promoter hypermethylation of cancer-related genes in the plasma may be a useful tool for the detection of breast cancer. PMID:19956520

  16. Spontaneous formation of tumorigenic hybrids between breast cancer and multipotent stromal cells is a source of tumor heterogeneity.

    Science.gov (United States)

    Rappa, Germana; Mercapide, Javier; Lorico, Aurelio

    2012-06-01

    Breast cancer progression involves cancer cell heterogeneity, with generation of invasive/metastatic breast cancer cells within populations of nonmetastatic cells of the primary tumor. Sequential genetic mutations, epithelial-to-mesenchymal transition, interaction with local stroma, and formation of hybrids between cancer cells and normal bone marrow-derived cells have been advocated as tumor progression mechanisms. We report herein the spontaneous in vitro formation of heterotypic hybrids between human bone marrow-derived multipotent stromal cells (MSCs) and two different breast carcinoma cell lines, MDA-MB-231 (MDA) and MA11. Hybrids showed predominantly mesenchymal morphological characteristics, mixed gene expression profiles, and increased DNA ploidy. Both MA11 and MDA hybrids were tumorigenic in immunodeficient mice, and some MDA hybrids had an increased metastatic capacity. Both in culture and as xenografts, hybrids underwent DNA ploidy reduction and morphological reversal to breast carcinoma-like morphological characteristics, while maintaining a mixed breast cancer-mesenchymal expression profile. Analysis of coding single-nucleotide polymorphisms by RNA sequencing revealed genetic contributions from both parental partners to hybrid tumors and metastasis. Because MSCs migrate and localize to breast carcinoma, our findings indicate that formation of MSC-breast cancer cell hybrids is a potential mechanism of the generation of invasive/metastatic breast cancer cells. Our findings reconcile the fusion theory of cancer progression with the common observation that breast cancer metastases are generally aneuploid, but not tetraploid, and are histopathologically similar to the primary neoplasm. Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  17. Electric Field Analysis of Breast Tumor Cells

    Directory of Open Access Journals (Sweden)

    V. Gowri Sree

    2011-01-01

    Full Text Available An attractive alternative treatment for malignant tumors that are refractive to conventional therapies, such as surgery, radiation, and chemotherapy, is electrical-pulse-mediated drug delivery. Electric field distribution of tissue/tumor is important for effective treatment of tissues. This paper deals with the electric field distribution study of a tissue model using MAXWELL 3D Simulator. Our results indicate that tumor tissue had lower electric field strength compared to normal cells, which makes them susceptible to electrical-pulse-mediated drug delivery. This difference could be due to the altered properties of tumor cells compared to normal cells, and our results corroborate this.

  18. Surgical options for Chinese patients with early invasive breast cancer: Data from the Hong Kong Breast Cancer Registry

    Directory of Open Access Journals (Sweden)

    Sharon W.W. Chan

    2017-11-01

    Conclusion: Chinese patients have lower BCS and breast reconstruction rate. Besides cultural difference, patient-related factors such as age, education, marital status, mammography screening, the use of private medical facilities, and clinical characteristics including smaller tumor size and peripherally located tumor were significant predictors for type of surgical treatments in Chinese women with early breast cancer.

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

    NARCIS (Netherlands)

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

    2014-01-01

    textabstractInvasive 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

  20. Ki-67 marker useful for classification of malignant invasive ductal breast cancer

    Directory of Open Access Journals (Sweden)

    Irmawati Hassan

    2015-12-01

    The study showed that invasive ductal breast cancer with high Ki-67 index was significantly associated with high grade of malignacy. The high Ki-67 marker index can be used for classification of the grade of malignancy of invasive ductal breast cancer.

  1. Tumor tissue protein signatures reflect histological grade of breast cancer.

    Science.gov (United States)

    Skoog, Petter; Ohlsson, Mattias; Fernö, Mårten; Rydén, Lisa; Borrebaeck, Carl A K; Wingren, Christer

    2017-01-01

    Histological grade is one of the most commonly used prognostic factors for patients diagnosed with breast cancer. However, conventional grading has proven technically challenging, and up to 60% of the tumors are classified as histological grade 2, which represents a heterogeneous cohort less informative for clinical decision making. In an attempt to study and extend the molecular puzzle of histologically graded breast cancer, we have in this pilot project searched for additional protein biomarkers in a new space of the proteome. To this end, we have for the first time performed protein expression profiling of breast cancer tumor tissue, using recombinant antibody microarrays, targeting mainly immunoregulatory proteins. Thus, we have explored the immune system as a disease-specific sensor (clinical immunoproteomics). Uniquely, the results showed that several biologically relevant proteins reflecting histological grade could be delineated. In more detail, the tentative biomarker panels could be used to i) build a candidate model classifying grade 1 vs. grade 3 tumors, ii) demonstrate the molecular heterogeneity among grade 2 tumors, and iii) potentially re-classify several of the grade 2 tumors to more like grade 1 or grade 3 tumors. This could, in the long-term run, lead to improved prognosis, by which the patients could benefit from improved tailored care.

  2. Tumor associated macrophage × cancer cell hybrids may acquire cancer stem cell properties in breast cancer.

    Directory of Open Access Journals (Sweden)

    Jingxian Ding

    Full Text Available Breast cancer is one of the most frequently diagnosed cancers among women, and metastasis makes it lethal. Tumor-associated macrophages (TAMs that acquire an alternatively activated macrophage (M2 phenotype may promote metastasis. However, the underlying mechanisms are still elusive. Here, we examined how TAMs interact with breast cancer cells to promote metastasis. Immunohistochemistry was used to examine the expression of the M2-specific antigen CD163 in paraffin-embedded mammary carcinoma blocks to explore fusion events in breast cancer patients. U937 cells were used as a substitute for human monocytes, and these cells differentiated into M2 macrophages following phorbol 12-myristate 13-acetate (PMA and M-CSF stimulation. M2 macrophages and the breast cancer cell lines MCF-7 and MDA-MB-231 fused in the presence of 50% polyethylene glycol. Hybrids were isolated by fluorescence-activated cell sorting, and the relevant cell biological properties were compared with their parental counterparts. Breast cancer stem cell (BCSC-related markers were quantified by immunofluorescence staining, RT-PCR, quantitative RT-PCR and/or western blotting. The tumor-initiating and metastatic capacities of the hybrids and their parental counterparts were assessed in NOD/SCID mice. We found that the CD163 expression rate in breast cancer tissues varied significantly and correlated with estrogen receptor status (p0.05. Characterization of the fusion hybrids revealed a more aggressive phenotype, including increased migration, invasion and tumorigenicity, but reduced proliferative ability, compared with the parental lines. The hybrids also gained a CD44(+CD24(-/low phenotype and over-expressed epithelial-mesenchymal transition-associated genes. These results indicate that TAMs may promote breast cancer metastasis through cell fusion, and the hybrids may gain a BCSC phenotype.

  3. Compromised margins following mastectomy for stage I-III invasive breast cancer.

    Science.gov (United States)

    Yu, Jennifer; Al Mushawah, Fatema; Taylor, Marie E; Cyr, Amy E; Gillanders, William E; Aft, Rebecca L; Eberlein, Timothy J; Gao, Feng; Margenthaler, Julie A

    2012-09-01

    We investigated factors associated with positive margins following mastectomy and the impact on outcomes. We identified 240 patients with stage I-III invasive breast cancer who underwent mastectomy from 1999 to 2009. Data included patient and tumor characteristics, pathologic margin assessment, and outcomes. Margin positivity was defined as the presence of in situ or invasive malignancy at any margin. Descriptive statistics were used for data summary and were compared using χ(2). Of the 240 patients, 132 (55%) had a simple mastectomy with sentinel lymph node biopsy and 108 (45%) had a modified radical mastectomy. Overall, 21 patients (9%) had positive margins, including 12 (57%) with one positive margin, 3 (14%) with two positive margins, and 6 (29%) with three or more positive margins. The most commonly affected margin was the deep margin (48% of patients). Eight of the 21 patients (38%) received adjuvant chest wall irradiation. There were no differences between patients who had a positive margin and those who did not with respect to patient age, race, percentage of in situ component, tumor size, tumor grade, lymphovascular invasion, or immunostain profile (P > 0.05 for all). None of the patients with positive margins experienced a local recurrence. Positive margins following mastectomy occurred in nearly 10% of our patients. No specific patient or tumor characteristics predicted a risk for having a positive margin. Despite the finding that only approximately 40% of patients received adjuvant radiation in the setting of a positive margin, no local recurrences have been observed. Copyright © 2012 Elsevier Inc. All rights reserved.

  4. Malignant phyllodes tumor of the breast: treatment and prognosis.

    Science.gov (United States)

    Mituś, Jerzy; Reinfuss, Marian; Mituś, Jerzy W; Jakubowicz, Jerzy; Blecharz, Pawel; Wysocki, Wojciech M; Skotnicki, Piotr

    2014-01-01

    Surgery remains the mainstay of the treatment in patients with malignant phyllodes tumor of the breast (MPTB); however, the extent of surgery (breast conserving surgery [BCS] versus mastectomy) and the role of adjuvant radiotherapy have been controversial. We report a single institution's experience with MPTB. We discuss controversial therapeutic aspects of this rare tumor. Seventy patients with MPTB treated primarily with surgery were evaluated. The mean age was 50 years (21-76), and the mean size of the tumor was 6 cm. Thirty-four (48.6%) patients were treated with total mastectomy, and 36 (51.4%) were treated with BCS (lumpectomy or wide local excision). Microscopic surgical margins were free of tumor in all cases. In 64 (91.4%) patients, margins were ≥1 cm. Remaining 6 (8.6%) patients treated with BCS margins were tumor-free margin ≥1 cm) and BCS with irradiation (tumor-free margin tumor-free margins cannot be obtained by BCS. Adjuvant radiotherapy may be considered if tumor-free margins are <1 cm. © 2014 Wiley Periodicals, Inc.

  5. Modeling the Effect of Tumor Size in Early Breast Cancer

    Science.gov (United States)

    Verschraegen, Claire; Vinh-Hung, Vincent; Cserni, Gábor; Gordon, Richard; Royce, Melanie E.; Vlastos, Georges; Tai, Patricia; Storme, Guy

    2005-01-01

    Summary Background Data: The purpose of this study was to determine the type of relationship between tumor size and mortality in early breast carcinoma. Methods: The data was abstracted from 83,686 cases registered in the Surveillance, Epidemiology, and End Results Program of women diagnosed with primary breast carcinoma between 1988 and 1997 presenting with a T1–T2 lesion and no metastasis in whom axillary node dissection was performed: 58,070 women were node-negative (N0) and 25,616 were node-positive (N+). End point was death from any cause. Tumor size was modeled as a continuous variable by proportional hazards using a generalized additive models procedure. Results: Functionally, a Gompertzian expression exp(-exp(-(size-15)/10)) provided a good fit to the effect of tumor size (in millimeters) on mortality, irrespective of nodal status. Quantitatively, for tumor size between 3 and 50 mm, the increase of crude cumulative death rate (number of observed deaths divided by the number of patients at risk) increased with size from 10% to 25% for N0 and from 20% to 40% for N+. Conclusions: The functional relationship of tumor size with mortality is concordant with current knowledge of tumor growth. However, its qualitative and quantitative independence of nodal status is in contradiction with the prevailing concept of sequential disease progression from primary tumor to regional nodes. This argues against the perception that nodal metastases are caused by the primary tumor. PMID:15650642

  6. ABCG2 is a potential marker of tumor-initiating cells in breast cancer.

    Science.gov (United States)

    Sicchieri, Renata Danielle; da Silveira, Willian Abraham; Mandarano, Larissa Raquel Mouro; de Oliveira, Tatiane Mendes Gonçalves; Carrara, Hélio Humberto Angotti; Muglia, Valdair Francisco; de Andrade, Jurandyr Moreira; Tiezzi, Daniel Guimarães

    2015-12-01

    The existence of tumor-initiating cells (TICs) within solid tumors has been hypothesized to explain tumor heterogeneity and resistance to cancer therapy. In breast cancer, the expression of CD44 and CD24 and the activity of aldehyde dehydrogenase 1 (ALDH1) can be used to selectively isolate a cell population enriched in TICs. However, the ideal marker to identify TICs has not been established. The aim of this study was to evaluate the expression of novel potential markers for TIC in breast carcinoma. We prospectively analyzed the expression of CD44, CD24, ABCG2, and CXCR4, and the activity of ALDH1 by using flow cytometry in 48 invasive ductal carcinomas from locally advanced and metastatic breast cancer patients who were administered primary chemotherapy. A mammosphere assay was employed in 30 samples. The relationship among flow cytometric analyses, ABCG2 gene expression, and clinical and pathological responses to therapy was analyzed. The GSE32646 database was analyzed in silico to identify genes associated with tumors with low and high ABCG2 expression. We observed that the presence of ABCG2(+) cells within the primary tumor was the only marker to predict the formation of mammospheres in vitro (R (2) = 0.15, p = 0.029). Quantitative polymerase chain reaction (qPCR) revealed a positive correlation between ABCG2 expression and the presence of ABCG2(+) cells within the primary tumor. The expression of ABCG2 was predictive of the response to neoadjuvant chemotherapy in our experiments and in the GSE32646 dataset (p = 0.04 and p = 0.002, respectively). The in silico analysis demonstrated that ABCG2(Up) breast cancer samples have a slower cell cycle and a higher expression of membrane proteins but a greater potential for chromosomal instability, metastasis, immune evasion, and resistance to hypoxia. Such genetic characteristics are compatible with highly aggressive and resistant tumors. Our results support the hypothesis that the presence of ABCG2

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

    Directory of Open Access Journals (Sweden)

    Suhail Mahmoud M

    2011-12-01

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

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

    Science.gov (United States)

    2011-01-01

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

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

    Science.gov (United States)

    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

    2016-04-04

    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.

  10. Crosstalk between chemokine receptor CXCR4 and cannabinoid receptor CB2 in modulating breast cancer growth and invasion.

    Directory of Open Access Journals (Sweden)

    Mohd W Nasser

    Full Text Available BACKGROUND: Cannabinoids bind to cannabinoid receptors CB(1 and CB(2 and have been reported to possess anti-tumorigenic activity in various cancers. However, the mechanisms through which cannabinoids modulate tumor growth are not well known. In this study, we report that a synthetic non-psychoactive cannabinoid that specifically binds to cannabinoid receptor CB(2 may modulate breast tumor growth and metastasis by inhibiting signaling of the chemokine receptor CXCR4 and its ligand CXCL12. This signaling pathway has been shown to play an important role in regulating breast cancer progression and metastasis. METHODOLOGY/PRINCIPAL FINDINGS: We observed high expression of both CB(2 and CXCR4 receptors in breast cancer patient tissues by immunohistochemical analysis. We further found that CB(2-specific agonist JWH-015 inhibits the CXCL12-induced chemotaxis and wound healing of MCF7 overexpressing CXCR4 (MCF7/CXCR4, highly metastatic clone of MDA-MB-231 (SCP2 and NT 2.5 cells (derived from MMTV-neu by using chemotactic and wound healing assays. Elucidation of the molecular mechanisms using various biochemical techniques and confocal microscopy revealed that JWH-015 treatment inhibited CXCL12-induced P44/P42 ERK activation, cytoskeletal focal adhesion and stress fiber formation, which play a critical role in breast cancer invasion and metastasis. In addition, we have shown that JWH-015 significantly inhibits orthotopic tumor growth in syngenic mice in vivo using NT 2.5 cells. Furthermore, our studies have revealed that JWH-015 significantly inhibits phosphorylation of CXCR4 and its downstream signaling in vivo in orthotopic and spontaneous breast cancer MMTV-PyMT mouse model systems. CONCLUSIONS/SIGNIFICANCE: This study provides novel insights into the crosstalk between CB(2 and CXCR4/CXCL12-signaling pathways in the modulation of breast tumor growth and metastasis. Furthermore, these studies indicate that CB(2 receptors could be used for developing

  11. Sensitivity of Breast Tumors to Oncolytic Viruses

    National Research Council Canada - National Science Library

    Ahmed, Maryam

    2006-01-01

    ...). Studies have shown that matrix (M) protein mutants of VSV such as rM51R-M virus are excellent candidates for anti-tumor therapies due to the ability of these viruses to target and kill tumor cells while sparing normal cells...

  12. Caffeine mediates sustained inactivation of breast cancer-associated myofibroblasts via up-regulation of tumor suppressor genes.

    Science.gov (United States)

    Al-Ansari, Mysoon M; Aboussekhra, Abdelilah

    2014-01-01

    Active cancer-associated fibroblasts (CAFs) or myofibroblasts play important roles not only in the development and progression of breast carcinomas, but also in their prognosis and treatment. Therefore, targeting these cells through suppressing their supportive procarcinogenic paracrine effects is mandatory for improving the current therapies that are mainly targeting tumor cells. To this end, we investigated the effect of the natural and pharmacologically safe molecule, caffeine, on CAF cells and their various procarcinogenic effects. We have shown here that caffeine up-regulates the tumor suppressor proteins p16, p21, p53 and Cav-1, and reduces the expression/secretion of various cytokines (IL-6, TGF-β, SDF-1 and MMP-2), and down-regulates α-SMA. Furthermore, caffeine suppressed the migratory/invasiveness abilities of CAF cells through PTEN-dependent Akt/Erk1/2 inactivation. Moreover, caffeine reduced the paracrine pro-invasion/-migration effects of CAF cells on breast cancer cells. These results indicate that caffeine can inactivate breast stromal myofibroblasts. This has been confirmed by showing that caffeine also suppresses the paracrine pro-angiogenic effect of CAF cells through down-regulating HIF-1αand its downstream effector VEGF-A. Interestingly, these effects were sustained in absence of caffeine. The present findings provide a proof of principle that breast cancer myofibroblasts can be inactivated, and thereby caffeine may provide a safe and effective prevention against breast tumor growth/recurrence through inhibition of the procarcinogenic effects of active stromal fibroblasts.

  13. Ovarian granulosa cell tumor and increased risk of breast cancer.

    Science.gov (United States)

    Hammer, Anne; Lauszus, Finn F; Petersen, Astrid C

    2013-12-01

    Granulosa cell tumor of the ovary (GCT) is a rare neoplasm. The tumor often secretes estrogens and then presents at an earlier stage due to hormone-related symptoms. GCT women are at increased risk of endometrial carcinoma, but there is only limited information about GCTs and potential association to other hormone-related neoplasms such as breast cancer. We conducted a retrospective follow-up study on 163 women with GCT. Medical records and histological sections were reviewed and a search in the pathology registry performed. Eight [95% confidence interval (CI); 3.4-15.8] GCT women were diagnosed with a breast neoplasm; one with Paget's disease of the nipple and seven with breast carcinoma. Based on calculations using incidence rates on breast cancer among Danish women, we would have expected 2.5 cases of breast cancer. The odds ratio was 3.3 (95% CI, 1.6-6.6), suggesting an increased risk of breast cancer in GCT women. © 2013 Nordic Federation of Societies of Obstetrics and Gynecology.

  14. Percutaneous Image-Guided Ablation of Breast Tumors: An Overview

    OpenAIRE

    Sag, Alan A.; Maybody, Majid; Comstock, Christopher; Solomon, Stephen B.

    2014-01-01

    Percutaneous non-surgical image-guided ablation is emerging as an adjunct or alternative to surgery in the management of benign and malignant breast tumors. This review covers the current state of the literature regarding percutaneous image-guided ablation modalities, clinical factors regarding patient selection, and future directions for research.

  15. Percutaneous image-guided ablation of breast tumors: an overview.

    Science.gov (United States)

    Sag, Alan A; Maybody, Majid; Comstock, Christopher; Solomon, Stephen B

    2014-06-01

    Percutaneous non-surgical image-guided ablation is emerging as an adjunct or alternative to surgery in the management of benign and malignant breast tumors. This review covers the current state of the literature regarding percutaneous image-guided ablation modalities, clinical factors regarding patient selection, and future directions for research.

  16. Invasive lobular carcinoma of the breast: MRI pathological correlation following bilateral total mastectomy.

    Science.gov (United States)

    Stivalet, Aude; Luciani, Alain; Pigneur, Frederic; Dao, Thu Ha; Beaussart, Pauline; Merabet, Zahira; Perlbarg, Julie; Meyblum, Evelyne; Baranes, Laurence; Calitchi, Elie; Lepage, Christophe; Belkacemi, Yazid; Lagrange, Jean-Leon; Lantieri, Laurent; Rahmouni, Alain

    2012-05-01

    Invasive lobular carcinoma (ILC) is more often multifocal and bilateral than invasive ductal carcinoma. MRI is usually recommended for detection of all ILC sites. The performance of known diagnostic breast MRI criteria for ILC characterization has not been evaluated to date using bilateral mastectomy specimens as gold standard. To determine the value of BI-RADS 2006 MRI criteria for ILC detection and characterization, using pathological examination of bilateral mastectomy specimens as the reference standard. Between 2004 and 2007, we retrospectively included all patients with pathologically documented ILC referred to our institution for bilateral mastectomy and preoperative bilateral breast MRI. The location, diameter, and characteristics (BI-RADS) of all lesions were compared with pathological findings. The sensitivity and positive predictive value of bilateral breast MRI for the diagnosis of ILC were calculated. Association of MRI BI-RADS categorical variables and characterization of ILC were assessed (Fisher exact test). Among 360 patients treated for ILC in 2004-2007, 15 patients qualified for this study. Thirty-one ILC foci were found on pathological examination (30 ipsilateral and 1 contralateral tumor; mean diameter 23 mm; range 2-60 mm) and all were identified on MRI, with 90% of masses and 10% non-mass-like enhancements; MRI features significantly associated with ILC included absence of smooth margins (P = 0.02) and rim-shaped enhancement (P = 0.039). Enhancement kinetics of the 31 foci were evenly distributed among wash-out, plateau, and persistent profiles. Eleven additional lesions were seen on MRI, mainly corresponding to fibrocystic disease; 91% presented as masses and 9% had a wash-out profile. Based on the 2006 BI-RADS criteria, breast MRI shows a high sensitivity for ILC detection, at the expense of a 26% false-positive rate, suggesting that a pathological proof by US- or MR-guided biopsy is required in case of suspicious MRI images in this context.

  17. Invasive lobular carcinoma of the breast: MRI pathological correlation following bilateral total mastectomy

    Energy Technology Data Exchange (ETDEWEB)

    Stivalet, Aude; Pigneur, Frederic (AP-HP, Groupe Henri Mondor Albert Chenevier, Imagerie Medicale, Creteil (France)); Luciani, Alain (AP-HP, Groupe Henri Mondor Albert Chenevier, Imagerie Medicale, Creteil (France); INSERM Unite U 955, Equipe 17, Univ. Paris Est Creteil, Creteil (France)), email: alain.luciani@hmn.aphp.fr (and others)

    2012-05-15

    Background: Invasive lobular carcinoma (ILC) is more often multifocal and bilateral than invasive ductal carcinoma. MRI is usually recommended for detection of all ILC sites. The performance of known diagnostic breast MRI criteria for ILC characterization has not been evaluated to date using bilateral mastectomy specimens as gold standard. Purpose: To determine the value of BI-RADS 2006 MRI criteria for ILC detection and characterization, using pathological examination of bilateral mastectomy specimens as the reference standard. Material and Methods: Between 2004 and 2007, we retrospectively included all patients with pathologically documented ILC referred to our institution for bilateral mastectomy and preoperative bilateral breast MRI. The location, diameter, and characteristics (BI-RADS) of all lesions were compared with pathological findings. The sensitivity and positive predictive value of bilateral breast MRI for the diagnosis of ILC were calculated. Association of MRI BI-RADS categorical variables and characterization of ILC were assessed (Fisher exact test). Results: Among 360 patients treated for ILC in 2004-2007, 15 patients qualified for this study. Thirty-one ILC foci were found on pathological examination (30 ipsilateral and 1 contralateral tumor; mean diameter 23 mm; range 2-60 mm) and all were identified on MRI, with 90% of masses and 10% non-mass-like enhancements; MRI features significantly associated with ILC included absence of smooth margins (P = 0.02) and rim-shaped enhancement (P = 0.039). Enhancement kinetics of the 31 foci were evenly distributed among wash-out, plateau, and persistent profiles. Eleven additional lesions were seen on MRI, mainly corresponding to fibrocystic disease; 91% presented as masses and 9% had a wash-out profile. Conclusion: Based on the 2006 BI-RADS criteria, breast MRI shows a high sensitivity for ILC detection, at the expense of a 26% false-positive rate, suggesting that a pathological proof by US- or MR

  18. Tetrathiomolybdate inhibits head and neck cancer metastasis by decreasing tumor cell motility, invasiveness and by promoting tumor cell anoikis

    Directory of Open Access Journals (Sweden)

    Merajver Sofia D

    2010-08-01

    Full Text Available Abstract Background The metastatic spread of solid tumors is directly or indirectly responsible for most cancer-related deaths. Tumor metastasis is very complex and this process requires a tumor cell to acquire enhanced motility, invasiveness and anoikis resistance to successfully establish a tumor at a distal site. Metastatic potential of tumor cells is directly correlated with the expression levels of several angiogenic cytokines. Copper is a mandatory cofactor for the function of many of these angiogenic mediators as well as other proteins that play an important role in tumor cell motility and invasiveness. We have previously shown that tetrathiomolybdate (TM is a potent chelator of copper and it mediates its anti-tumor effects by suppressing tumor angiogenesis. However, very little is known about the effect of TM on tumor cell function and tumor metastasis. In this study, we explored the mechanisms underlying TM-mediated inhibition of tumor metastasis. Results We used two in vivo models to examine the effects of TM on tumor metastasis. Animals treated with TM showed a significant decrease in lung metastasis in both in vivo models as compared to the control group. In addition, tumor cells from the lungs of TM treated animals developed significantly smaller colonies and these colonies had significantly fewer tumor cells. TM treatment significantly decreased tumor cell motility and invasiveness by inhibiting lysyl oxidase (LOX activity, FAK activation and MMP2 levels. Furthermore, TM treatment significantly enhanced tumor cell anoikis by activating p38 MAPK cell death pathway and by downregulating XIAP survival protein expression. Conclusions Taken together, these results suggest that TM is a potent suppressor of head and neck tumor metastasis by modulating key regulators of tumor cell motility, invasiveness and anoikis resistance.

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

    Science.gov (United States)

    Schmidt, Marjanka K; Hogervorst, Frans; van Hien, Richard; Cornelissen, Sten; Broeks, Annegien; Adank, Muriel A; Meijers, Hanne; Waisfisz, Quinten; Hollestelle, Antoinette; Schutte, Mieke; van den Ouweland, Ans; Hooning, Maartje; Andrulis, Irene L; Anton-Culver, Hoda; Antonenkova, Natalia N; Antoniou, Antonis C; Arndt, Volker; Bermisheva, Marina; Bogdanova, Natalia V; Bolla, Manjeet K; Brauch, Hiltrud; Brenner, Hermann; Brüning, Thomas; Burwinkel, Barbara; Chang-Claude, Jenny; Chenevix-Trench, Georgia; Couch, Fergus J; Cox, Angela; Cross, Simon S; Czene, Kamila; Dunning, Alison M; Fasching, Peter A; Figueroa, Jonine; Fletcher, Olivia; Flyger, Henrik; Galle, Eva; García-Closas, Montserrat; Giles, Graham G; Haeberle, Lothar; Hall, Per; Hillemanns, Peter; Hopper, John L; Jakubowska, Anna; John, Esther M; Jones, Michael; Khusnutdinova, Elza; Knight, Julia A; Kosma, Veli-Matti; Kristensen, Vessela; Lee, Andrew; Lindblom, Annika; Lubinski, Jan; Mannermaa, Arto; Margolin, Sara; Meindl, Alfons; Milne, Roger L; Muranen, Taru A; Newcomb, Polly A; Offit, Kenneth; Park-Simon, Tjoung-Won; Peto, Julian; Pharoah, Paul D P; Robson, Mark; Rudolph, Anja; Sawyer, Elinor J; Schmutzler, Rita K; Seynaeve, Caroline; Soens, Julie; Southey, Melissa C; Spurdle, Amanda B; Surowy, Harald; Swerdlow, Anthony; Tollenaar, Rob A E M; Tomlinson, Ian; Trentham-Dietz, Amy; Vachon, Celine; Wang, Qin; Whittemore, Alice S; Ziogas, Argyrios; van der Kolk, Lizet; Nevanlinna, Heli; Dörk, Thilo; Bojesen, Stig; Easton, Douglas F

    2016-08-10

    CHEK2*1100delC is a well-established breast cancer risk variant that is most prevalent in European populations; however, there are limited data on risk of breast cancer by age and tumor subtype, which limits its usefulness in breast cancer risk prediction. We aimed to generate tumor subtype- and age-specific risk estimates by using data from the Breast Cancer Association Consortium, including 44,777 patients with breast cancer and 42,997 controls from 33 studies genotyped for CHEK2*1100delC. CHEK2*1100delC genotyping was mostly done by a custom Taqman assay. Breast cancer odds ratios (ORs) for CHEK2*1100delC carriers versus noncarriers were estimated by using logistic regression and adjusted for study (categorical) and age. Main analyses included patients with invasive breast cancer from population- and hospital-based studies. Proportions of heterozygous CHEK2*1100delC carriers in controls, in patients with breast cancer from population- and hospital-based studies, and in patients with breast cancer from familial- and clinical genetics center-based studies were 0.5%, 1.3%, and 3.0%, respectively. The estimated OR for invasive breast cancer was 2.26 (95%CI, 1.90 to 2.69; P = 2.3 × 10(-20)). The OR was higher for estrogen receptor (ER)-positive disease (2.55 [95%CI, 2.10 to 3.10; P = 4.9 × 10(-21)]) than it was for ER-negative disease (1.32 [95%CI, 0.93 to 1.88; P = .12]; P interaction = 9.9 × 10(-4)). The OR significantly declined with attained age for breast cancer overall (P = .001) and for ER-positive tumors (P = .001). Estimated cumulative risks for development of ER-positive and ER-negative tumors by age 80 in CHEK2*1100delC carriers were 20% and 3%, respectively, compared with 9% and 2%, respectively, in the general population of the United Kingdom. These CHEK2*1100delC breast cancer risk estimates provide a basis for incorporating CHEK2*1100delC into breast cancer risk prediction models and into guidelines for intensified screening and follow-up. © 2016

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

    Science.gov (United States)

    Hogervorst, Frans; van Hien, Richard; Cornelissen, Sten; Broeks, Annegien; Adank, Muriel A.; Meijers, Hanne; Waisfisz, Quinten; Hollestelle, Antoinette; Schutte, Mieke; van den Ouweland, Ans; Hooning, Maartje; Andrulis, Irene L.; Anton-Culver, Hoda; Antonenkova, Natalia N.; Antoniou, Antonis C.; Arndt, Volker; Bermisheva, Marina; Bogdanova, Natalia V.; Bolla, Manjeet K.; Brauch, Hiltrud; Brenner, Hermann; Brüning, Thomas; Burwinkel, Barbara; Chang-Claude, Jenny; Chenevix-Trench, Georgia; Couch, Fergus J.; Cox, Angela; Cross, Simon S.; Czene, Kamila; Dunning, Alison M.; Fasching, Peter A.; Figueroa, Jonine; Fletcher, Olivia; Flyger, Henrik; Galle, Eva; García-Closas, Montserrat; Giles, Graham G.; Haeberle, Lothar; Hall, Per; Hillemanns, Peter; Hopper, John L.; Jakubowska, Anna; John, Esther M.; Jones, Michael; Khusnutdinova, Elza; Knight, Julia A.; Kosma, Veli-Matti; Kristensen, Vessela; Lee, Andrew; Lindblom, Annika; Lubinski, Jan; Mannermaa, Arto; Margolin, Sara; Meindl, Alfons; Milne, Roger L.; Muranen, Taru A.; Newcomb, Polly A.; Offit, Kenneth; Park-Simon, Tjoung-Won; Peto, Julian; Pharoah, Paul D.P.; Robson, Mark; Rudolph, Anja; Sawyer, Elinor J.; Schmutzler, Rita K.; Seynaeve, Caroline; Soens, Julie; Southey, Melissa C.; Spurdle, Amanda B.; Surowy, Harald; Swerdlow, Anthony; Tollenaar, Rob A.E.M.; Tomlinson, Ian; Trentham-Dietz, Amy; Vachon, Celine; Wang, Qin; Whittemore, Alice S.; Ziogas, Argyrios; van der Kolk, Lizet; Nevanlinna, Heli; Dörk, Thilo; Bojesen, Stig; Easton, Douglas F.

    2016-01-01

    Purpose CHEK2*1100delC is a well-established breast cancer risk variant that is most prevalent in European populations; however, there are limited data on risk of breast cancer by age and tumor subtype, which limits its usefulness in breast cancer risk prediction. We aimed to generate tumor subtype- and age-specific risk estimates by using data from the Breast Cancer Association Consortium, including 44,777 patients with breast cancer and 42,997 controls from 33 studies genotyped for CHEK2*1100delC. Patients and Methods CHEK2*1100delC genotyping was mostly done by a custom Taqman assay. Breast cancer odds ratios (ORs) for CHEK2*1100delC carriers versus noncarriers were estimated by using logistic regression and adjusted for study (categorical) and age. Main analyses included patients with invasive breast cancer from population- and hospital-based studies. Results Proportions of heterozygous CHEK2*1100delC carriers in controls, in patients with breast cancer from population- and hospital-based studies, and in patients with breast cancer from familial- and clinical genetics center–based studies were 0.5%, 1.3%, and 3.0%, respectively. The estimated OR for invasive breast cancer was 2.26 (95%CI, 1.90 to 2.69; P = 2.3 × 10−20). The OR was higher for estrogen receptor (ER)–positive disease (2.55 [95%CI, 2.10 to 3.10; P = 4.9 × 10−21]) than it was for ER-negative disease (1.32 [95%CI, 0.93 to 1.88; P = .12]; P interaction = 9.9 × 10−4). The OR significantly declined with attained age for breast cancer overall (P = .001) and for ER-positive tumors (P = .001). Estimated cumulative risks for development of ER-positive and ER-negative tumors by age 80 in CHEK2*1100delC carriers were 20% and 3%, respectively, compared with 9% and 2%, respectively, in the general population of the United Kingdom. Conclusion These CHEK2*1100delC breast cancer risk estimates provide a basis for incorporating CHEK2*1100delC into breast cancer risk prediction models and into

  1. Thyroid hormone receptor alpha (TRa) tissue expression in ductal invasive breast cancer: A study combining quantitative immunohistochemistry with digital slide image analysis.

    Science.gov (United States)

    Charalampoudis, P; Agrogiannis, G; Kontzoglou, K; Kouraklis, G; Sotiropoulos, G C

    2017-08-01

    In breast cancer, hormonal receptors hold promise for developing novel targeted therapies. The thyroid exerts its actions via the thyroid hormone receptors alpha and beta. The clinical significance of the expression of thyroid hormone receptors in breast cancer is unclear. We studied thyroid hormone receptor alpha (TRa) expression in 82 samples from 41 women with ductal invasive breast cancer and no thyroid disease. We performed quantitative immunohistochemistry with digital image analysis and correlated TRa expression with clinicopathological parameters. TRa was expressed in both normal breast epithelium and breast cancer, but expression in breast cancer was significantly lower. TRa was expressed significantly less in larger and grade III tumors. Conversely, breast cancers with lymphovascular invasion showed increased TRa expression compared to cancers without lymphovascular invasion. TRa expression was not significantly different between node-positive and node-negative breast cancers, or among different hormonal profiles and intrinsic subtypes. This is the first-in-human study to combine quantitative immunohistochemistry with image analysis to study TRa expression in women with ductal invasive breast cancer and no clinical or biochemical evidence of thyroid dysfunction. We confirm that TRa is expressed in both normal and malignant breast epithelium and suggest that TRa expression is downregulated during breast carcinogenesis. Larger and higher grade breast cancers demonstrate partial loss in TRa expression. Alterations in TRa expression take place even in the absence of clinical or biochemical thyroid disease. The underlying mechanism of these findings and their potential significance in survival and relapse mandate further research. Copyright © 2017 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

  2. Inhibitory effect of miR-184 on the potential of proliferation and invasion in human glioma and breast cancer cells in vitro.

    Science.gov (United States)

    Feng, Ren; Dong, Lei

    2015-01-01

    MiR-184 was an important suppressor to tumor cells proliferation and invasion and some studies show that it was down-regulated in aggressive human tumor cells and a potential tumor therapy target through expression of miR-184 results in reduced tumor cell aggressiveness. In this study, miR-184 showed an inhibitive activity of glioma U87MG cell line and breast cancer MCF-7 cell line in proliferation and invasion by MTS and transwell assay. We found that the miR-184 also could arrest cell cycle and adhesion by up-regulating the expression of p53 and p21 and activity of caspase-3/8, suppressing the expression of SND1, MMP-2/9, CD44 and activity of AKT/NF-κB pathway. The results showed that miR-184 could be a potential target for glioma and breast cancer treatment.

  3. Mass spectrometry images acylcarnitines, phosphatidylcholines, and sphingomyelin in MDA-MB-231 breast tumor models[S

    Science.gov (United States)

    Chughtai, Kamila; Jiang, Lu; Greenwood, Tiffany R.; Glunde, Kristine; Heeren, Ron M. A.

    2013-01-01

    The lipid compositions of different breast tumor microenvironments are largely unknown due to limitations in lipid imaging techniques. Imaging lipid distributions would enhance our understanding of processes occurring inside growing tumors, such as cancer cell proliferation, invasion, and metastasis. Recent developments in MALDI mass spectrometry imaging (MSI) enable rapid and specific detection of lipids directly from thin tissue sections. In this study, we performed multimodal imaging of acylcarnitines, phosphatidylcholines (PC), a lysophosphatidylcholine (LPC), and a sphingomyelin (SM) from different microenvironments of breast tumor xenograft models, which carried tdTomato red fluorescent protein as a hypoxia-response element-driven reporter gene. The MSI molecular lipid images revealed spatially heterogeneous lipid distributions within tumor tissue. Four of the most-abundant lipid species, namely PC(16:0/16:0), PC(16:0/18:1), PC(18:1/18:1), and PC(18:0/18:1), were localized in viable tumor regions, whereas LPC(16:0/0:0) was detected in necrotic tumor regions. We identified a heterogeneous distribution of palmitoylcarnitine, stearoylcarnitine, PC(16:0/22:1), and SM(d18:1/16:0) sodium adduct, which colocalized primarily with hypoxic tumor regions. For the first time, we have applied a multimodal imaging approach that has combined optical imaging and MALDI-MSI with ion mobility separation to spatially localize and structurally identify acylcarnitines and a variety of lipid species present in breast tumor xenograft models. PMID:22930811

  4. Administrative data algorithms to identify second breast cancer events following early-stage invasive breast cancer.

    Science.gov (United States)

    Chubak, Jessica; Yu, Onchee; Pocobelli, Gaia; Lamerato, Lois; Webster, Joe; Prout, Marianne N; Ulcickas Yood, Marianne; Barlow, William E; Buist, Diana S M

    2012-06-20

    Studies of breast cancer outcomes rely on the identification of second breast cancer events (recurrences and second breast primary tumors). Cancer registries often do not capture recurrences, and chart abstraction can be infeasible or expensive. An alternative is using administrative health-care data to identify second breast cancer events; however, these algorithms must be validated against a gold standard. We developed algorithms using data from 3152 women in an integrated health-care system who were diagnosed with stage I or II breast cancer in 1993-2006. Medical record review served as the gold standard for second breast cancer events. Administrative data used in algorithm development included procedures, diagnoses, prescription fills, and cancer registry records. We randomly divided the cohort into training and testing samples and used a classification and regression tree analysis to build algorithms for classifying women as having or not having a second breast cancer event. We created several algorithms for researchers to use based on the relative importance of sensitivity, specificity, and positive predictive value (PPV) in future studies. The algorithm with high specificity and PPV had 89% sensitivity (95% confidence interval [CI] = 84% to 92%), 99% specificity (95% CI = 98% to 99%), and 90% PPV (95% CI = 86% to 94%); the high-sensitivity algorithm had 96% sensitivity (95% CI = 93% to 98%), 95% specificity (95% CI = 94% to 96%), and 74% PPV (95% CI = 68% to 78%). Algorithms based on administrative data can identify second breast cancer events with high sensitivity, specificity, and PPV. The algorithms presented here promote efficient outcomes research, allowing researchers to prioritize sensitivity, specificity, or PPV in identifying second breast cancer events.

  5. Immunohistochemical Assessment of Expression of Centromere Protein—A (CENPA) in Human Invasive Breast Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Rajput, Ashish B. [Department of Pathology and Molecular Medicine, Queen' s University, Kingston, ON K7L 3N6 (Canada); Hu, Nianping [Cancer Research institute, Queen' s University, Kingston, ON K7L 3N6 (Canada); Varma, Sonal; Chen, Chien-Hung [Department of Pathology and Molecular Medicine, Queen' s University, Kingston, ON K7L 3N6 (Canada); Ding, Keyue [NCIC Clinical Trials Group, Queen' s University, Kingston, ON K7L 3N6 (Canada); Park, Paul C. [Department of Pathology and Molecular Medicine, Queen' s University, Kingston, ON K7L 3N6 (Canada); Chapman, Judy-Anne W. [NCIC Clinical Trials Group, Queen' s University, Kingston, ON K7L 3N6 (Canada); SenGupta, Sandip K. [Department of Pathology and Molecular Medicine, Queen' s University, Kingston, ON K7L 3N6 (Canada); Madarnas, Yolanda [Cancer Research institute, Queen' s University, Kingston, ON K7L 3N6 (Canada); Department of Oncology, Cancer Center of Southeastern Ontario, Kingston, ON K7L 2V7 (Canada); Elliott, Bruce E.; Feilotter, Harriet E., E-mail: feilotth@kgh.kari.net [Department of Pathology and Molecular Medicine, Queen' s University, Kingston, ON K7L 3N6 (Canada)

    2011-12-06

    Abnormal cell division leading to the gain or loss of entire chromosomes and consequent genetic instability is a hallmark of cancer. Centromere protein –A (CENPA) is a centromere-specific histone-H3-like variant gene involved in regulating chromosome segregation during cell division. CENPA is one of the genes included in some of the commercially available RNA based prognostic assays for breast cancer (BCa)—the 70 gene signature MammaPrint{sup ®} and the five gene Molecular Grade Index (MGI{sup SM}). Our aim was to assess the immunohistochemical (IHC) expression of CENPA in normal and malignant breast tissue. Clinically annotated triplicate core tissue microarrays of 63 invasive BCa and 20 normal breast samples were stained with a monoclonal antibody against CENPA and scored for percentage of visibly stained nuclei. Survival analyses with Kaplan–Meier (KM) estimate and Cox proportional hazards regression models were applied to assess the associations between CENPA expression and disease free survival (DFS). Average percentage of nuclei visibly stained with CENPA antibody was significantly higher (p = 0.02) in BCa than normal tissue. The 3-year DFS in tumors over-expressing CENPA (>50% stained nuclei) was 79% compared to 85% in low expression tumors (<50% stained nuclei). On multivariate analysis, IHC expression of CENPA showed weak association with DFS (HR > 60.07; p = 0.06) within our small cohort. To the best of our knowledge, this is the first published report evaluating the implications of increased IHC expression of CENPA in paraffin embedded breast tissue samples. Our finding that increased CENPA expression may be associated with shorter DFS in BCa supports its exploration as a potential prognostic biomarker.

  6. Immunohistochemical Assessment of Expression of Centromere Protein—A (CENPA in Human Invasive Breast Cancer

    Directory of Open Access Journals (Sweden)

    Bruce E. Elliott

    2011-12-01

    Full Text Available Abnormal cell division leading to the gain or loss of entire chromosomes and consequent genetic instability is a hallmark of cancer. Centromere protein –A (CENPA is a centromere-specific histone-H3-like variant gene involved in regulating chromosome segregation during cell division. CENPA is one of the genes included in some of the commercially available RNA based prognostic assays for breast cancer (BCa—the 70 gene signature MammaPrint® and the five gene Molecular Grade Index (MGISM. Our aim was to assess the immunohistochemical (IHC expression of CENPA in normal and malignant breast tissue. Clinically annotated triplicate core tissue microarrays of 63 invasive BCa and 20 normal breast samples were stained with a monoclonal antibody against CENPA and scored for percentage of visibly stained nuclei. Survival analyses with Kaplan–Meier (KM estimate and Cox proportional hazards regression models were applied to assess the associations between CENPA expression and disease free survival (DFS. Average percentage of nuclei visibly stained with CENPA antibody was significantly higher (p = 0.02 in BCa than normal tissue. The 3-year DFS in tumors over-expressing CENPA (>50% stained nuclei was 79% compared to 85% in low expression tumors ( 60.07; p = 0.06 within our small cohort. To the best of our knowledge, this is the first published report evaluating the implications of increased IHC expression of CENPA in paraffin embedded breast tissue samples. Our finding that increased CENPA expression may be associated with shorter DFS in BCa supports its exploration as a potential prognostic biomarker.

  7. Comparison of Treatment Outcome Between Invasive Lobular and Ductal Carcinomas in Patients Receiving Partial Breast Irradiation With Intraoperative Electrons.

    Science.gov (United States)

    Leonardi, Maria Cristina; Maisonneuve, Patrick; Mastropasqua, Mauro Giuseppe; Cattani, Federica; Fanetti, Giuseppe; Morra, Anna; Lazzari, Roberta; Bazzani, Federica; Caputo, Mariangela; Rotmensz, Nicole; Gerardi, Marianna Alessandra; Ricotti, Rosalinda; Enrica Galimberti, Viviana; Veronesi, Paolo; Dicuonzo, Samantha; Viale, Giuseppe; Jereczek-Fossa, Barbara Alicja; Orecchia, Roberto

    2017-09-01

    To investigate the local outcome of patients after accelerated partial breast irradiation with intraoperative electrons (IORT) for invasive lobular carcinoma (ILC) compared with invasive ductal carcinoma (IDC). From 1999 to 2007, 2173 patients were treated with breast-conserving surgery and IORT (21 Gy/1 fraction) as the sole local treatment: 252 patients with ILC (11.6%) were compared with 1921 patients with IDC in terms of local control. Compared with the IDC subgroup, patients with ILC had a low-risk profile and were more hormone responsive. The 5- and 10-year in-breast tumor reappearance (IBTR) rates were 5.5% and 14.4%, respectively, for the IDC group and 7.5% and 21.8%, respectively, for the ILC group (log-rank P=.03). The excess risk of IBTR associated with ILC was particularly high for small tumors (≤1 cm: hazard ratio [HR], 2.24; 95% confidence interval [CI], 1.03-4.85), elderly patients (60-69 years: HR, 2.27; 95% CI, 1.11-4.63; ≥70 years: HR, 3.28; 95% CI, 1.08-10.0), low-grade tumors (grade 1: HR, 3.50; 95% CI, 1.05-11.7), and luminal A molecular subtype (HR, 3.18; 95% CI, 1.49-6.77). Among the ILC histologic variants, no difference between classic and nonclassic subgroups was observed, although the signet ring cell and solid variants had the worst local control. Despite a favorable tumor profile, accelerated partial breast irradiation with IORT led to a higher incidence of IBTRs in patients with ILC compared with those with IDC. Our institutional experience emphasized the importance of the size of the irradiation field, pointing to the use of larger collimators, even when dealing with small tumors, to improve local control. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. ID genes mediate tumor reinitiation during breast cancer lung metastasis

    Science.gov (United States)

    Gupta, Gaorav P.; Perk, Jonathan; Acharyya, Swarnali; de Candia, Paola; Mittal, Vivek; Todorova-Manova, Katia; Gerald, William L.; Brogi, Edi; Benezra, Robert; Massagué, Joan

    2007-01-01

    The establishment of distant metastases depends on the capacity of small numbers of cancer cells to regenerate a tumor after entering a target tissue. The mechanisms that confer this capacity remain to be defined. Here we identify a role for the transcriptional inhibitors of differentiation Id1 and Id3 as selective mediators of lung metastatic colonization in the triple negative [TN, i.e., lacking expression of estrogen receptor and progesterone receptor, and lacking Her2 (human epidermal growth factor receptor 2) amplification] subgroup of human breast cancer. Although broad expression of Id1 has recently been documented in tumors of the rare metaplastic subtype, here we report that rare Id1-expressing cells are also present in the more common TN subset of human breast tumors but not in other subtypes. We also provide evidence that Id1 expression is enriched in clinically obtained hormone receptor negative lung metastases. Functional studies demonstrate that Id1 and its closely related family member Id3 are required for tumor initiating functions, both in the context of primary tumor formation and during metastatic colonization of the lung microenvironment. In vivo characterization of lung metastatic progression reveals that Id1 and Id3 facilitate sustained proliferation during the early stages of metastatic colonization, subsequent to extravasation into the lung parenchyma. These results shed light on the proliferative mechanisms that initiate metastatic colonization, and they implicate Id1 and Id3 as mediators of this malignant function in the TN subgroup of breast cancers. PMID:18048329

  9. CDDO-Me Redirects Activation of Breast Tumor Associated Macrophages.

    Science.gov (United States)

    Ball, Michael S; Shipman, Emilie P; Kim, Hyunjung; Liby, Karen T; Pioli, Patricia A

    2016-01-01

    Tumor-associated macrophages can account for up to 50% of the tumor mass in breast cancer patients and high TAM density is associated with poor clinical prognosis. Because TAMs enhance tumor growth, development, and metastatic potential, redirection of TAM activation may have significant therapeutic benefit. Our studies in primary human macrophages and murine breast TAMs suggest that the synthetic oleanane triterpenoid CDDO-methyl ester (CDDO-Me) reprograms the activation profile of TAMs from tumor-promoting to tumor-inhibiting. We show that CDDO-Me treatment inhibits expression of IL-10 and VEGF in stimulated human M2 macrophages and TAMs but increases expression of TNF-α and IL-6. Surface expression of CD206 and CD163, which are characteristic of M2 activation, is significantly attenuated by CDDO-Me. In contrast, CDDO-Me up-regulates surface expression of HLA-DR and CD80, which are markers of M1 activation, and importantly potentiates macrophage activation of autologous T cells but inhibits endothelial cell vascularization. These results show for the first time that CDDO-Me redirects activation of M2 macrophages and TAMs from immune-suppressive to immune-stimulatory, and implicate a role for CDDO-Me as an immunotherapeutic in the treatment of breast and potentially other types of cancer.

  10. SMARCAD1 knockdown uncovers its role in breast cancer cell migration, invasion, and metastasis.

    Science.gov (United States)

    Al Kubaisy, Elham; Arafat, Kholoud; De Wever, Olivier; Hassan, Ahmed H; Attoub, Samir

    2016-09-01

    Breast cancer is the most common cancer seen in women worldwide and breast cancer patients are at high risk of recurrence in the form of metastatic disease. Identification of genes associated with invasion and metastasis is crucial in order to develop novel anti-metastasis targeted therapy. It has been demonstrated that the DEAD-BOX helicase DP103 was implicated in breast cancer invasion and metastasis. SMARCAD1 is also a DEAD/H box-containing helicase, suggested to play a role in genetic instability. However, its involvement in cancer migration, invasion, and metastasis has never been explored. Using two different designs of shRNA targeting SMARCAD1, we investigated the impact of SMARCAD1 knockdown on the migration, invasion, and metastasis potential of the breast cancer cells MDA-MB-231 and T47D. We observed that SMARCAD1 knockdown in the invasive breast cancer cells MDA-MB-231, unlike in the non-invasive breast cancer cells T47D, was associated with an increased cell-cell adhesion and a significant decrease in cell migration, invasion, and metastasis due at least in part to a strong inhibition of STAT3 phosphorylation. These results indicate that SMARCAD1 is involved in breast cancer metastasis and can be a promising target for metastatic breast cancer therapy.

  11. A novel method to understand tumor cell invasion: integrating extracellular matrix mimicking layers in microfluidic chips by "selective curing".

    Science.gov (United States)

    Eslami Amirabadi, H; SahebAli, S; Frimat, J P; Luttge, R; den Toonder, J M J

    2017-10-17

    A major challenge in studying tumor cell invasion into its surrounding tissue is to identify the contribution of individual factors in the tumor microenvironment (TME) to the process. One of the important elements of the TME is the fibrous extracellular matrix (ECM) which is known to influence cancer cell invasion, but exactly how remains unclear. Therefore, there is a need for new models to unravel mechanisms behind the tumor-ECM interaction. In this article, we present a new microfabrication method, called selective curing, to integrate ECM-mimicking layers between two microfluidic channels. This method enables us to study the effect of 3D matrices with controlled architecture, beyond the conventionally used hydrogels, on cancer invasion in a controlled environment. As a proof of principle, we have integrated two electrospun Polycaprolactone (PCL) matrices with different fiber diameters in one chip. We then studied the 3D migration of MDA-MB-231 breast cancer cells into the matrices under the influence of a chemotactic gradient. The results show that neither the invasion distance nor the general cell morphology is affected significantly by the difference in fiber size of these matrices. The cells however do produce longer and more protrusions in the matrix with smaller fiber size. This microfluidic system enables us to study the influence of other factors in the TME on cancer development as well as other biological applications as it provides a controlled compartmentalized environment compatible with cell culturing.

  12. Downregulated long non-coding RNA MEG3 in breast cancer regulates proliferation, migration and invasion by depending on p53’s transcriptional activity

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Lin [West Biostatistics and Cost-effectiveness Research Center, Medical Insurance Office, West China Hospital of Sichuan University, 610041, Sichuan (China); Li, Yu [Department of Anesthesiology, West China Hospital, Sichuan University, 610041, Sichuan (China); Yang, Bangxiang, E-mail: b19933009@qq.coom [Department of Pain Management, West China Hospital of Sichuan University, 610041, Sichuan (China)

    2016-09-09

    Long non-coding RNAs (lncRNAs) was found to play critical roles in tumorigenesis, hence, screen of tumor-related lncRNAs, identification of their biological roles is important for understanding the processes of tumorigenesis. In this study, we identified the expressing difference of several tumor-related lncRNAs in breast cancer samples and found that, MEG3, which is downregulated in non-small cell lung cancer (NSCLC) tumor tissues, is also downregulated in breast cancer samples compared with adjacent tissues. For figuring out the effect of MEG3 in breast cancer cells MCF7 and MB231, we overexpressed MEG3 in these cells, and found that it resulted the inhibition of proliferation, colony formation, migration and invasion capacities by enhancing p53’s transcriptional activity on its target genes, including p21, Maspin and KAI1. MEG3 presented similar effects in MB157, which is a p53-null breast cancer cell line, when functional p53 but not p53R273H mutant, which lacks transcriptional activity, was introduced. Surprisingly, overexpression of MEG3 activates p53’s transcriptional activity by decreasing MDM2’s transcription level, and thus stabilizes and accumulates P53. Taken together, our findings indicate that MEG3 is downregulated in breast cancer tissues and affects breast cancer cells’ malignant behaviors, which indicate MEG3 a potential therapeutic target for breast cancer. - Highlights: • MEG3 RNA is widely downregulated in breast tumor tissue. • MEG3 regulates P53 indirectly through transcriptional regulation of MDM2. • Under unstressed condition, MEG3-related P53 accumulation transcriptionally activates p53’s target genes. • MEG3 expression level tightly regulates proliferation, colony formation, migration and invasion in breast tumor cells.

  13. Elevated cyclin B2 expression in invasive breast carcinoma is associated with unfavorable clinical outcome

    Directory of Open Access Journals (Sweden)

    Shubbar Emman

    2013-01-01

    Full Text Available Abstract Background Breast cancer is a potentially fatal malignancy in females despite the improvement in therapeutic techniques. The identification of novel molecular signatures is needed for earlier detection, monitoring effects of treatment, and predicting prognosis. We have previously used microarray analysis to identify differentially expressed genes in aggressive breast tumors. The purpose of the present study was to investigate the prognostic value of the candidate biomarkers CCNB2, ASPM, CDCA7, KIAA0101, and SLC27A2 in breast cancer. Methods The expression levels and subcellular localization of the CCNB2, ASPM, CDCA7, KIAA0101, and SLC27A2 proteins were measured using immunohistochemistry (IHC on a panel of 80 primary invasive breast tumors. Furthermore, the mRNA levels of CCNB2, KIAA0101, and SLC27A2 were subsequently examined by qRT-PCR to validate IHC results. Patient disease-specific survival (DSS was evaluated in correlation to protein levels using the Kaplan-Meier method. Multivariate Cox regression analysis was used to determine the impact of aberrant protein expression of the candidate biomarkers on patient DSS and to estimate the hazard ratio at 8-year follow-up. Results Elevated cytoplasmic CCNB2 protein levels were strongly associated with short-term disease-specific survival of breast cancer patients (≤ 8 years; PP= 0.04. However, no association with other clinicopathological parameters was observed. Multivariate Cox regression analysis specified that CCNB2 protein expression is an independent prognostic marker of DSS in breast cancer. The predictive ability of several classical clinicopathological parameters was improved when used in conjunction with CCNB2 protein expression (C-index = 0.795 in comparison with a model without CCNB2 expression (C-index = 0.698. The protein levels of ASPM, CDCA7, KIAA0101, and SLC27A2 did not correlate with any clinicopathological parameter and had no influence on DSS. However, a significant

  14. Polyclonal breast cancer metastases arise from collective dissemination of keratin 14-expressing tumor cell clusters.

    Science.gov (United States)

    Cheung, Kevin J; Padmanaban, Veena; Silvestri, Vanesa; Schipper, Koen; Cohen, Joshua D; Fairchild, Amanda N; Gorin, Michael A; Verdone, James E; Pienta, Kenneth J; Bader, Joel S; Ewald, Andrew J

    2016-02-16

    Recent genomic studies challenge the conventional model that each metastasis must arise from a single tumor cell and instead reveal that metastases can be composed of multiple genetically distinct clones. These intriguing observations raise the question: How do polyclonal metastases emerge from the primary tumor? In this study, we used multicolor lineage tracing to demonstrate that polyclonal seeding by cell clusters is a frequent mechanism in a common mouse model of breast cancer, accounting for >90% of metastases. We directly observed multicolored tumor cell clusters across major stages of metastasis, including collective invasion, local dissemination, intravascular emboli, circulating tumor cell clusters, and micrometastases. Experimentally aggregating tumor cells into clusters induced a >15-fold increase in colony formation ex vivo and a >100-fold increase in metastasis formation in vivo. Intriguingly, locally disseminated clusters, circulating tumor cell clusters, and lung micrometastases frequently expressed the epithelial cytoskeletal protein, keratin 14 (K14). RNA-seq analysis revealed that K14(+) cells were enriched for desmosome and hemidesmosome adhesion complex genes, and were depleted for MHC class II genes. Depletion of K14 expression abrogated distant metastases and disrupted expression of multiple metastasis effectors, including Tenascin C (Tnc), Jagged1 (Jag1), and Epiregulin (Ereg). Taken together, our findings reveal K14 as a key regulator of metastasis and establish the concept that K14(+) epithelial tumor cell clusters disseminate collectively to colonize distant organs.

  15. Polyclonal breast cancer metastases arise from collective dissemination of keratin 14-expressing tumor cell clusters

    Science.gov (United States)

    Cheung, Kevin J.; Padmanaban, Veena; Silvestri, Vanesa; Schipper, Koen; Cohen, Joshua D.; Fairchild, Amanda N.; Gorin, Michael A.; Verdone, James E.; Pienta, Kenneth J.; Bader, Joel S.; Ewald, Andrew J.

    2016-01-01

    Recent genomic studies challenge the conventional model that each metastasis must arise from a single tumor cell and instead reveal that metastases can be composed of multiple genetically distinct clones. These intriguing observations raise the question: How do polyclonal metastases emerge from the primary tumor? In this study, we used multicolor lineage tracing to demonstrate that polyclonal seeding by cell clusters is a frequent mechanism in a common mouse model of breast cancer, accounting for >90% of metastases. We directly observed multicolored tumor cell clusters across major stages of metastasis, including collective invasion, local dissemination, intravascular emboli, circulating tumor cell clusters, and micrometastases. Experimentally aggregating tumor cells into clusters induced a >15-fold increase in colony formation ex vivo and a >100-fold increase in metastasis formation in vivo. Intriguingly, locally disseminated clusters, circulating tumor cell clusters, and lung micrometastases frequently expressed the epithelial cytoskeletal protein, keratin 14 (K14). RNA-seq analysis revealed that K14+ cells were enriched for desmosome and hemidesmosome adhesion complex genes, and were depleted for MHC class II genes. Depletion of K14 expression abrogated distant metastases and disrupted expression of multiple metastasis effectors, including Tenascin C (Tnc), Jagged1 (Jag1), and Epiregulin (Ereg). Taken together, our findings reveal K14 as a key regulator of metastasis and establish the concept that K14+ epithelial tumor cell clusters disseminate collectively to colonize distant organs. PMID:26831077

  16. Infrared Spectra of Human Breast Tumor Tissue and Experimental Animal Tumors

    Science.gov (United States)

    Tolstorozhev, G. B.; Belkov, M. V.; Skornyakov, I. V.; Pekhnyo, V. I.; Kozachkova, A. N.; Tsarik, H. V.; Kutsenko, I. P.; Sharykina, N. I.; Butra, V. A.

    2015-01-01

    We have used Fourier transform IR spectroscopy methods to conduct comparative studies of human breast tumors and sarcoma 180 tumor grafted into mice. The IR spectral parameters used to identify tumor tissue in mice with the sarcoma 180 strain proved to be identical to the parameters for human breast tissue in cancer. In the presence of a malignant tumor in humans, the most intense C=O vibrational bands in the protein molecules are observed in the interval 1710-1680 cm-1. For a benign tumor, in the IR spectra of breast tissue the intense bands are located in the interval 1670-1650 cm-1. We spectroscopically monitored the diagnosis and the chemotherapy process using the model of sarcoma 180 in mice. As the therapeutic drugs, we used synthesized coordination compounds based on palladium complexes with diphosphonic acid derivatives. We demonstrate the promising potential of palladium complexes with zoledronic acid as an effective cytostatic. In therapy using a palladium complex with zoledronic acid, the effect of tumor growth inhibition is accompanied by a change in its spectral characteristics. The parameters of the IR spectra for tumor tissue after treatment are close to those of the IR spectra for healthy tissue.

  17. Metastatic pattern of invasive lobular carcinoma of the breast-Emphasis on gastric metastases.

    Science.gov (United States)

    El-Hage, Ali; Ruel, Carolanne; Afif, Wahiba; Wissanji, Hussein; Hogue, Jean-Charles; Desbiens, Christine; Leblanc, Guy; Poirier, Éric

    2016-10-01

    Breast invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) have different metastatic patterns, but the exact pattern of metastases from ILC is poorly known. This study aimed to determine the frequency of ILC metastases in atypical locations, with an emphasis on gastric metastases. Patients with ILC treated at the Saint-Sacrement Hospital (Quebec City, Canada) and the Maisonneuve-Rosemont Hospital (Montreal, Canada) between January 2003 and December 2009 were retrospectively reviewed. Demographic, clinical, and follow-up data were retrieved from the medical charts. Metastases that were diagnosed during follow-up were recorded. Among the 481 patients with ILC, 74 (15.4%) were diagnosed with metastases after a median follow-up of 46 months. Among these 74 patients, 41.9% had metastases in atypical sites. Five patients were diagnosed with histologically confirmed gastric metastases of ILC. Metastases of breast ILC to atypical sites might be more frequent than previously reported. Clinicians should keep a high level of suspicion when a patient with a history of ILC develops digestive symptoms. It is important to differentiate metastases from a primary GI tumor by using immunohistochemical markers. J. Surg. Oncol. 2016;114:543-547. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  18. Benchmarking clinical practice quality: an audit of ipsilateral breast tumor recurrence in patients managed for T1/T2 breast carcinoma.

    Science.gov (United States)

    Suttie, Clare; Back, Michael; Donovan, Jennifer; Holecek, Milan; Morgia, Marita; Guo, Lesley; Lamoury, Gillian

    2016-12-01

    Breast conserving surgery and adjuvant radiotherapy has equivalent oncological outcomes to mastectomy and is the standard of care for treatment of early-stage invasive breast cancer. Auditing is an essential component of ongoing quality assurance and clinical governance. It also serves to identify patient and tumor factors that have prognostic and therapeutic implications. The aim of this paper is to report on the clinical audit of treatment outcomes for patients undergoing adjuvant radiation treatment for early breast cancer at the Northern Sydney Cancer Care Centre. A total of 1252 patients with T1/2 breast cancer received adjuvant radiation treatment between January 2003 and December 2010. Medical records, including the departmental database, were reviewed to extract pathological, treatment, patient and clinical details. Median follow-up was 54 months (mean 56.4 months). Sixty-six (5.27%) patients died from breast cancer, and 27 (2.16%) patients died from other disease. Twenty-three (1.84%) patients were alive with metastatic disease, 7 (0.56%) patients were alive following ipsilateral breast tumor recurrence and 7 (0.56%) patients were alive with nodal recurrence. 9 (0.72%) patients were alive with contralateral breast cancer. Documented rates of late toxicity were low: 6.8% of patients had grade 1 late toxicity and 1.6% of patients had grade 2-3 late toxicity. Our ipsilateral breast tumor recurrence rate of 0.56% is well within international standards, as is our toxicity rate. We propose that centralized data collection be implemented on a nation-wide level for breast cancer patients undergoing radiotherapy. Further research is planned to identify potential markers of radio-resistance, and allow tailoring of treatment technique to optimize oncological outcome. © 2016 John Wiley & Sons Australia, Ltd.

  19. Therapeutic effects of dendrosomal solanine on a metastatic breast tumor.

    Science.gov (United States)

    Mohsenikia, Maryam; Farhangi, Baharak; Alizadeh, Ali Mohammad; Khodayari, Hamid; Khodayari, Saeed; Khori, Vahid; Arjmand Abbassi, Yasaman; Vesovic, Milica; Soleymani, Ali; Najafi, Farhood

    2016-03-01

    Our previous studies showed that alpha-solanine can inhibit tumor growth in cell culture and animal models of breast cancer. However, solanine is insoluble in common solvents; therefore, we developed a special nanoparticle with high-capacity solubility. The present study is aimed to deliberate the therapeutic effects of dendrosomal solanine (DNS) on a metastatic breast tumor in vitro and in vivo. After DNS preparation and dosing procedures, forty-five mice were equally divided into five groups to investigate the anti-metastatic effects of DNS on mammary tumor-bearing mice. Compared to solanine, DNS significantly suppressed the proliferation of 4 T1 cells in a dose- and time-dependent manner. DNS showed a remarkable safety rate of up to 10mg/kg. A significant decrease in white blood-cell count was seen at 20mg/kg DNS in comparison with control animals. Mice treated with DNS had smaller tumor volume (mm(3)) in comparison with control and solanine groups. Moreover, the incidence of the breast tumor metastases was about 67% in the control animals, where as solanine and DNS 1mg/kg were about 22% and 0%, respectively. Furthermore, the number of metastases per mouse varied from one to three. The tissues of tumor, brain, liver, spleen, and lung showed higher expression levels of Bcl-2 but lower expression levels of Bax, MMP-2, MMP-9, mTOR, and Akt in DNS-treated mice than control and solanine groups. The findings suggest that DNS has a more impactful therapeutic effect than solanine on 4 T1-induced breast tumorigenesis via influencing the tissue microenvironment. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Elasticity, adhesion and tether extrusion on breast cancer cells provide a signature of their invasive potential.

    Science.gov (United States)

    Smolyakov, Georges; Thiebot, Bénédicte; Campillo, Clément C; Labdi, Sid; Séverac, Childérick; Pelta, Juan; Dague, Etienne

    2016-10-05

    We use single cell force spectroscopy to compare elasticity, adhesion and tether extrusion on four breast cancer cell lines with an increasing invasive potential. We perform cell attachment/detachment experiments either on fibronectin or on another cell using an Atomic Force Microscope. Our study on the membrane tether formation from cancer cells show that they are easier to extrude from aggressive invasive cells. Measured elastic modulus values confirm that more invasive cells are softer. Moreover, the adhesion force increases with the invasive potential. Our results provide a mechanical signature of breast cancer cells that correlates with their invasivity.

  1. Technical Note: Multipurpose CT, ultrasound, and MRI breast phantom for use in radiotherapy and minimally invasive interventions.

    Science.gov (United States)

    Ruschin, Mark; Davidson, Sean R H; Phounsy, William; Yoo, Tae Sun; Chin, Lee; Pignol, Jean-Philippe; Ravi, Ananth; McCann, Claire

    2016-05-01

    To develop a multipurpose gel-based breast phantom consisting of a simulated tumor with realistic imaging properties in CT, ultrasound and MRI, or a postsurgical cavity on CT. Applications for the phantom include: deformable image registration (DIR) quality assurance (QA), autosegmentation validation, and localization testing and training for minimally invasive image-guided procedures such as those involving catheter or needle insertion. A thermoplastic mask of a typical breast patient lying supine was generated and then filled to make an array of phantoms. The background simulated breast tissue consisted of 32.4 g each of ballistic gelatin (BG) powder and Metamusil™ (MM) dissolved in 800 ml of water. Simulated tumors were added using the following recipe: 12 g of barium sulfate (1.4% v/v) plus 0.000 14 g copper sulfate plus 0.7 g of MM plus 7.2 g of BG all dissolved in 75 ml of water. The phantom was evaluated quantitatively in CT by comparing Hounsfield units (HUs) with actual breast tissue. For ultrasound and MRI, the phantoms were assessed based on subjective image quality and signal-difference to noise (SDNR) ratio, respectively. The stiffness of the phantom was evaluated based on ultrasound elastography measurements to yield an average Young's modulus. In addition, subjective tactile assessment of phantom was performed under needle insertion. The simulated breast tissue had a mean background value of 24 HU on CT imaging, which more closely resembles fibroglandular tissue (40 HU) as opposed to adipose (-100 HU). The tumor had a mean CT number of 45 HU, which yielded a qualitatively realistic image contrast relative to the background either as an intact tumor or postsurgical cavity. The tumor appeared qualitatively realistic on ultrasound images, exhibiting hypoechoic characteristics compared to background. On MRI, the tumor exhibited a SDNR of 3.7. The average Young's modulus was computed to be 15.8 ± 0.7 kPa (1 SD). We have developed a process to

  2. Technical Note: Multipurpose CT, ultrasound, and MRI breast phantom for use in radiotherapy and minimally invasive interventions

    Energy Technology Data Exchange (ETDEWEB)

    Ruschin, Mark, E-mail: Mark.Ruschin@sunnybrook.ca; Chin, Lee; Ravi, Ananth; McCann, Claire [Department of Medical Physics, Sunnybrook Odette Cancer Centre, Toronto, Ontario M4N 3M5, Canada and Department of Radiation Oncology, University of Toronto, Toronto, Ontario M4N 3M5 (Canada); Davidson, Sean R. H. [Techna Institute, University Health Network, Toronto, Ontario M5G 1P5 (Canada); Phounsy, William [Department of Physics, Ryerson University, Toronto, Ontario M5B 2K3 (Canada); Yoo, Tae Sun [Institute of Health Policy, University of Toronto, Toronto, Ontario M5T 3M6 (Canada); Pignol, Jean-Philippe [Department of Radiation Oncology, Erasmus MC Cancer Institute, 3075 EA Rotterdam (Netherlands)

    2016-05-15

    Purpose: To develop a multipurpose gel-based breast phantom consisting of a simulated tumor with realistic imaging properties in CT, ultrasound and MRI, or a postsurgical cavity on CT. Applications for the phantom include: deformable image registration (DIR) quality assurance (QA), autosegmentation validation, and localization testing and training for minimally invasive image-guided procedures such as those involving catheter or needle insertion. Methods: A thermoplastic mask of a typical breast patient lying supine was generated and then filled to make an array of phantoms. The background simulated breast tissue consisted of 32.4 g each of ballistic gelatin (BG) powder and Metamusil™ (MM) dissolved in 800 ml of water. Simulated tumors were added using the following recipe: 12 g of barium sulfate (1.4% v/v) plus 0.000 14 g copper sulfate plus 0.7 g of MM plus 7.2 g of BG all dissolved in 75 ml of water. The phantom was evaluated quantitatively in CT by comparing Hounsfield units (HUs) with actual breast tissue. For ultrasound and MRI, the phantoms were assessed based on subjective image quality and signal-difference to noise (SDNR) ratio, respectively. The stiffness of the phantom was evaluated based on ultrasound elastography measurements to yield an average Young’s modulus. In addition, subjective tactile assessment of phantom was performed under needle insertion. Results: The simulated breast tissue had a mean background value of 24 HU on CT imaging, which more closely resembles fibroglandular tissue (40 HU) as opposed to adipose (−100 HU). The tumor had a mean CT number of 45 HU, which yielded a qualitatively realistic image contrast relative to the background either as an intact tumor or postsurgical cavity. The tumor appeared qualitatively realistic on ultrasound images, exhibiting hypoechoic characteristics compared to background. On MRI, the tumor exhibited a SDNR of 3.7. The average Young’s modulus was computed to be 15.8 ± 0.7 kPa (1 SD

  3. Monitoring of tumor growth and metastasis potential in MDA-MB-435s/tk-luc human breast cancer xenografts

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Y.-F. [Department of Radiological Sciences, National Yang-Ming University, 155, Sec. 2, Li-Nong Street, Pei-tou 112, Taipei, Taiwan (China); Lin, Y.-Y. [Department of Radiological Sciences, National Yang-Ming University, 155, Sec. 2, Li-Nong Street, Pei-tou 112, Taipei, Taiwan (China); Wang, H.-E. [Department of Radiological Sciences, National Yang-Ming University, 155, Sec. 2, Li-Nong Street, Pei-tou 112, Taipei, Taiwan (China); Liu, R.-S. [Department of Nuclear Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan (China); Nuclear Medicine Department, Veterans General Hospital, Taipei, Taiwan (China); Pang Fei [Department of Veterinary Medicine, National Taiwan University, Taipei, Taiwan (China); Hwang, J.-J. [Department of Radiological Sciences, National Yang-Ming University, 155, Sec. 2, Li-Nong Street, Pei-tou 112, Taipei, Taiwan (China)]. E-mail: jjhwang@ym.edu.tw

    2007-02-01

    Molecular imaging of reporter gene expression provides a rapid, sensitive and non-invasive monitoring of tumor behaviors. In this study, we reported the establishment of a novel animal model for longitudinal examination of tumor growth kinetics and metastatic spreading in vivo. The highly metastatic human breast carcinoma MDA-MB-435s cell line was engineered to stably express herpes simplex virus type 1 thymidine kinase (HSV-1-tk) and luciferase (luc). Both {sup 131}I-FIAU and D-luciferin were used as reporter probes. For orthotopic tumor formation, MDA-MB-435s/tk-luc cells were implanted into the first nipple of 6-week-old female NOD/SCID mice. For metastatic study, cells were injected via the lateral tail vein. Mice-bearing MDA-MB-435s/tk-luc tumors were scanned for tumor growth and metastatsis using Xenogen IVIS50 system. Gamma scintigraphy and whole-body autoradiography were also applied to confirm the tumor localization. The results of bioluminescence imaging as well as histopathological finding showed that tumors could be detected in femur, spine, ovary, lungs, kidney, adrenal gland, lymph nodes and muscle at 16 weeks post i.v. injection, and correlated photons could be quantified. This MDA-MB-435s/tk-luc human breast carcinoma-bearing mouse model combined with multimodalities of molecular imaging may facilitate studies on the molecular mechanisms of cancer invasion and metastasis.

  4. Monitoring of tumor growth and metastasis potential in MDA-MB-435s/ tk-luc human breast cancer xenografts

    Science.gov (United States)

    Chang, Ya-Fang; Lin, Yi-Yu; Wang, Hsin-Ell; Liu, Ren-Shen; Pang, Fei; Hwang, Jeng-Jong

    2007-02-01

    Molecular imaging of reporter gene expression provides a rapid, sensitive and non-invasive monitoring of tumor behaviors. In this study, we reported the establishment of a novel animal model for longitudinal examination of tumor growth kinetics and metastatic spreading in vivo. The highly metastatic human breast carcinoma MDA-MB-435s cell line was engineered to stably express herpes simplex virus type 1 thymidine kinase (HSV-1- tk) and luciferase ( luc). Both 131I-FIAU and D-luciferin were used as reporter probes. For orthotopic tumor formation, MDA-MB-435s/ tk-luc cells were implanted into the first nipple of 6-week-old female NOD/SCID mice. For metastatic study, cells were injected via the lateral tail vein. Mice-bearing MDA-MB-435s/ tk-luc tumors were scanned for tumor growth and metastatsis using Xenogen IVIS50 system. Gamma scintigraphy and whole-body autoradiography were also applied to confirm the tumor localization. The results of bioluminescence imaging as well as histopathological finding showed that tumors could be detected in femur, spine, ovary, lungs, kidney, adrenal gland, lymph nodes and muscle at 16 weeks post i.v. injection, and correlated photons could be quantified. This MDA-MB-435s/ tk-luc human breast carcinoma-bearing mouse model combined with multimodalities of molecular imaging may facilitate studies on the molecular mechanisms of cancer invasion and metastasis.

  5. Immunohistochemical and genetic exploration of incompatible A blood group antigen expression in invasive micropapillary breast carcinoma: A case report.

    Science.gov (United States)

    Zouine, S; Orfi, Z; Kojok, K; Benayad, S; Zaid, Y; Marnissi, F; Habti, N

    Invasive Micropapillary Carcinoma (IMPC) of the breast is a relatively rare subtype of invasive ductal carcinoma and represents the most inherently aggressive form. Expression of incompatible blood group A antigen in cancer of type O patients has been reported in several types of cancer, however, the biosynthetic mechanism and the genetic basis remain unclear until today. The aim of the present case report study was to evaluate the expression of incompatible blood group A antigen and to identify the genetic basis of this expression in IMPC of the breast. One patient blood group O with Invasive Micropapillary Carcinoma was screened at Pathology Department of University Hospital CHU Ibn Rochd, Casablanca. ABH antigens expression was assessed by immunohistochemistry. ABO genotyping was performed by allele specific primers PCR-ASP and Exon 6 of ABO gene was sequenced with Sanger method. H antigen was expressed in endothelial and epithelial cells of normal tissue. However, H antigen expression was lost in both invasive micropapillary carcinomas. A antigen was expressed in IMPC with approximately 80% of positive cells. Tumor DNA was genotyped as heterozygous A/O. In normal DNA, we identified a single frameshift deletion c.320delA p.(Glu107Glyfs*12), which is removed from tumor DNA. Our findings suggest that incompatible A antigen expression in IMPC is due to glycosyltransferase A encoded by an A allele which is derived from O allele with a deletion at the position 320. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  6. Giant breast tumors: Surgical management of phyllodes tumors, potential for reconstructive surgery and a review of literature

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    McKelvey Michael T

    2008-11-01

    Full Text Available Abstract Background Phyllodes tumors are biphasic fibroepithelial neoplasms of the breast. While the surgical management of these relatively uncommon tumors has been addressed in the literature, few reports have commented on the surgical approach to tumors greater than ten centimeters in diameter – the giant phyllodes tumor. Case presentation We report two cases of giant breast tumors and discuss the techniques utilized for pre-operative diagnosis, tumor removal, and breast reconstruction. A review of the literature on the surgical management of phyllodes tumors was performed. Conclusion Management of the giant phyllodes tumor presents the surgeon with unique challenges. The majority of these tumors can be managed by simple mastectomy. Axillary lymph node metastasis is rare, and dissection should be limited to patients with pathologic evidence of tumor in the lymph nodes.

  7. Aberrant expression of novel and previously described cell membrane markers in human breast cancer cell lines and tumors.

    Science.gov (United States)

    Huang, Huayi; Groth, Jeff; Sossey-Alaoui, Khalid; Hawthorn, Lesleyann; Beall, Stephanie; Geradts, Joseph

    2005-06-15

    In a previous gene expression array study, we identified some 300 genes that were differentially expressed in human epidermal growth factor receptor tyrosine kinase 2 (HER2)-positive versus HER2-negative breast cancer cells. We have now done validation experiments on a group of three cell membrane components that had previously not been implicated in breast cancer. We also studied the expression of three other cell membrane proteins known to play a role in mammary neoplasia. By immunohistochemistry, we examined up to 130 archival breast carcinomas for Celsr2, E-cadherin, Kai1, and CD9 expression. The expression levels of NET-6 and TROP-2 were determined by quantitative reverse transcription-PCR in a subset of frozen tumors. We also studied fresh pellets and paraffin-embedded cell buttons of nine human breast cell lines. The relationship between the expression of all six membrane proteins and a variety of pathologic and biological variables, including estrogen receptor, HER2, and epidermal growth factor receptor status, was also examined. The NET-6 gene was transfected into a low-expressing cell line, and the effect on cellular morphology, growth, and invasion in vitro was recorded. Celsr2 was down-regulated in one cell line and in 7% of breast cancers. E-cadherin, Kai1, and CD9 were down-regulated in 35%, 76%, and 79% of tumors, respectively, confirming the important role of these markers in human mammary neoplasia. In breast cancer cell lines and tissues, TROP-2 was generally expressed at low levels, although a few specimens showed relative overexpression. NET-6 levels were lower in HER2-negative breast carcinoma cells. In addition, NET-6 was markedly down-regulated in estrogen receptor-negative breast cancers, and expression was lowest in "basal-like" tumors. Ectopic expression of NET-6 in low-expressing MDA-MB-231 cells altered cellular morphology, inhibited growth in vitro, and decreased invasion in a Boyden chamber assay. We have confirmed the expression of

  8. Breast cancer tumor classification using LASSO method selection approach

    Energy Technology Data Exchange (ETDEWEB)

    Celaya P, J. M.; Ortiz M, J. A.; Martinez B, M. R.; Solis S, L. O.; Castaneda M, R.; Garza V, I.; Martinez F, M.; Ortiz R, J. M., E-mail: morvymm@yahoo.com.mx [Universidad Autonoma de Zacatecas, Av. Ramon Lopez Velarde 801, Col. Centro, 98000 Zacatecas, Zac. (Mexico)

    2016-10-15

    Breast cancer is one of the leading causes of deaths worldwide among women. Early tumor detection is key in reducing breast cancer deaths and screening mammography is the widest available method for early detection. Mammography is the most common and effective breast cancer screening test. However, the rate of positive findings is very low, making the radiologic interpretation monotonous and biased toward errors. In an attempt to alleviate radiological workload, this work presents a computer-aided diagnosis (CAD x) method aimed to automatically classify tumor lesions into malign or benign as a means to a second opinion. The CAD x methos, extracts image features, and classifies the screening mammogram abnormality into one of two categories: subject at risk of having malignant tumor (malign), and healthy subject (benign). In this study, 143 abnormal segmentation s (57 malign and 86 benign) from the Breast Cancer Digital Repository (BCD R) public database were used to train and evaluate the CAD x system. Percentile-rank (p-rank) was used to standardize the data. Using the LASSO feature selection methodology, the model achieved a Leave-one-out-cross-validation area under the receiver operating characteristic curve (Auc) of 0.950. The proposed method has the potential to rank abnormal lesions with high probability of malignant findings aiding in the detection of potential malign cases as a second opinion to the radiologist. (Author)

  9. Clinicopathologic characteristics and molecular subtypes of invasive papillary carcinoma of the breast: a large case study.

    Science.gov (United States)

    Liu, Zi Yu; Liu, Ning; Wang, Ya Hong; Yang, Cui Cui; Zhang, Jing; Lv, Shu Hua; Niu, Yun

    2013-01-01

    Although patients with invasive papillary carcinoma (IPC) often have favorable prognoses, it remains unclear whether this special type of breast cancer represents a distinct morphological entity with its own biological features and clinical behavior distinct from those of invasive ductal carcinoma (IDC) and whether its four molecular subtypes are associated with different prognoses. The study is a retrospective analysis of a large patient cohort from a single institution. 284 IPC samples were collected from January 2000 to May 2011. 300 IDC cases were selected randomly from 13,428 cases of IDC during the same periods. We assessed the clinicopathologic characteristics, molecular features, and prognostic value of IPC (n = 284) and compared them to those of IDC (n = 300). Clinicopathologic features and survival status of the four subtypes of IPC were also evaluated. IPC differed from IDC with respect to age upon diagnosis, tumor grade, lymph node status, and menopausal status (P IPC was associated with a better 5-year overall survival rate (OS) (92.77 vs. 87.95 %) and disease-free survival rate (DFS) (87.95 vs. 80.72 %) than IDC. Tumors of the luminal A subtype had a better 5-year OS (97.78 %) and DFS (95.56 %) than other subtypes. The biologic behavior of IPC is more favorable to patient outcome than that of IDC. The chance of pure IPC causing death without an intervening event of a different histologic type is exceptionally low. Luminal A subtypes have better outcomes when compared to the other subtypes.

  10. Rap2B promotes proliferation, migration, and invasion of human breast cancer through calcium-related ERK1/2 signaling pathway.

    Science.gov (United States)

    Di, Jiehui; Huang, Hui; Qu, Debao; Tang, Juangjuan; Cao, Wenjia; Lu, Zheng; Cheng, Qian; Yang, Jing; Bai, Jin; Zhang, Yanping; Zheng, Junnian

    2015-07-23

    Rap2B, a member of GTP-binding proteins, is widely upregulated in many types of tumors and promotes migration and invasion of human suprarenal epithelioma. However, the function of Rap2B in breast cancer is unknown. Expression of Rap2B was examined in breast cancer cell lines and human normal breast cell line using Western blot analysis. Using the CCK-8 cell proliferation assay, cell cycle analysis, and transwell migration assay, we also elucidated the role of Rap2B in breast cancer cell proliferation, migration, and invasion. Results showed that the expression of Rap2B is higher in tumor cells than in normal cells. Flow cytometry and Western blot analysis revealed that Rap2B elevates the intracellular calcium level and further promotes extracellular signal-related kinase (ERK) 1/2 phosphorylation. By contrast, calcium chelator BAPTM/AM and MEK inhibitor (U0126) can reverse Rap2B-induced ERK1/2 phosphorylation. Furthermore, Rap2B knockdown inhibits cell proliferation, migration, and invasion abilities via calcium related-ERK1/2 signaling. In addition, overexpression of Rap2B promotes cell proliferation, migration and invasion abilities, which could be neutralized by BAPTM/AM and U0126. Taken together, these findings shed light on Rap2B as a therapeutic target for breast cancer.

  11. Quantification of in vitro mesenchymal stem cell invasion into tumor spheroids using selective plane illumination microscopy.

    Science.gov (United States)

    Rühland, Svenja; Wechselberger, Alexandra; Spitzweg, Christine; Huss, Ralf; Nelson, Peter J; Harz, Hartmann

    2015-04-01

    Mesenchymal stem cell (MSC) homing and integration into tumors are under evaluation for clinical application. This approach requires the identification of conditions for optimal tumor invasion. We describe a tool for the in vitro comparison of parameters influencing invasion. Human MSC added to experimental tumor spheroids variably migrates toward the center of the structure. To determine MSC distribution inside the three-dimensional specimen, spatial analysis was performed using selective plane illumination microscopy. A standardized method to quantify and compare the invasion potential of variably treated MSC into experimental tumor environments allows efficient screening for optimizing conditions.

  12. Dissecting Tumor-Stromal Interactions in Breast Cancer Bone Metastasis

    Directory of Open Access Journals (Sweden)

    Yibin Kang

    2016-06-01

    Full Text Available Bone metastasis is a frequent occurrence in breast cancer, affecting more than 70% of late stage cancer patients with severe complications such as fracture, bone pain, and hypercalcemia. The pathogenesis of osteolytic bone metastasis depends on cross-communications between tumor cells and various stromal cells residing in the bone microenvironment. Several growth factor signaling pathways, secreted micro RNAs (miRNAs and exosomes are functional mediators of tumor-stromal interactions in bone metastasis. We developed a functional genomic approach to systemically identified molecular pathways utilized by breast cancer cells to engage the bone stroma in order to generate osteolytic bone metastasis. We showed that elevated expression of vascular cell adhesion molecule 1 (VCAM1 in disseminated breast tumor cells mediates the recruitment of pre-osteoclasts and promotes their differentiation to mature osteoclasts during the bone metastasis formation. Transforming growth factor β (TGF-β is released from bone matrix upon bone destruction, and signals to breast cancer to further enhance their malignancy in developing bone metastasis. We furthered identified Jagged1 as a TGF-β target genes in tumor cells that engaged bone stromal cells through the activation of Notch signaling to provide a positive feedback to promote tumor growth and to activate osteoclast differentiation. Substantially change in miRNA expression was observed in osteoclasts during their differentiation and maturation, which can be exploited as circulating biomarkers of emerging bone metastasis and therapeutic targets for the treatment of bone metastasis. Further research in this direction may lead to improved diagnosis and treatment strategies for bone metastasis.

  13. Correlation of serum intercellular adhesion molecule 1 and vascular endothelial growth factor with tumor grading and staging in breast cancer patients.

    Science.gov (United States)

    Haghi, Alireza Rastgoo; Vahedi, Amir; Shekarchi, Ali Akbar; Kamran, Aziz

    2017-01-01

    Breast cancer is the most common cancer among women. There are several prognostic factors for this disease. The aim of this article is to explore the correlation of serum level of vascular endothelial growth factor (VEGF) and intercellular adhesion molecule 1 (ICAM1) with tumor, node, metastasis staging and grading of breast cancer. Serum samples of 51 patients with breast cancer were assessed with enzyme-linked immunosorbent assay for the level of VEGF and ICAM1 preoperatively. After the operation, histopathologic specimens stained with hematoxylin and eosin were evaluated for tumor size, histopathologic subtype, grade, lymph node, vascular and lymphatic involvement. Then, the correlation of tumor stage and grade and serum level of markers was analyzed. There was no significant correlation between serum level of markers with vascular invasions, lymph node involvement, and menstruation. There was a weak correlation between tumor size and serum level of ICAM1 with Pearson score correlation, but there was no significant correlation with VEGF. There was no significant correlation between tumor grading and staging with the level of markers. There was a significant correlation between the level of VEGF and ICAM1 and histologic type of tumors in invasive through in situ tumors. Levels of VEGF and ICAM1 can be used as a predictor of tumor invasion and also for target therapy.

  14. Raloxifene reduces triple-negative breast cancer tumor growth and decreases EGFR expression.

    Science.gov (United States)

    Taurin, Sebastien; Allen, Kirstie M; Scandlyn, Marissa J; Rosengren, Rhonda J

    2013-09-01

    The poor prognosis of patients with triple-negative breast cancer (TNBC) and the lack of targeted treatments have raised the need for alternative therapies. Previous studies have suggested an effect of raloxifene, a selective estrogen receptor modulator that is independent of the estrogen receptor (ER). Therefore, we assessed the therapeutic value of raloxifene in TNBC mouse models. Mice received a daily oral treatment with different doses of raloxifene. Tumor progression was monitored weekly; in addition microvessel density, proliferation, migration and invasion, apoptosis and tumorigenicity were analyzed. This study demonstrates that raloxifene (0.85 mg/kg) prevents TNBC tumor growth and induces tumor regression. The treated tumors showed a 54% decreased microvascular density and proliferation and a 7-fold increase in apoptosis. The underlying therapeutic mechanism of raloxifene was associated with a 27-fold decrease in the expression of the epidermal growth factor receptor (EGFR). Moreover, raloxifene promoted the translocation of EGFR into endosomes associated with decreased cell migration, cell