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Sample records for invasive breast carcinomatransition

  1. 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.

  2. 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

  3. [Lobular neoplasms and invasive lobular breast cancer].

    Science.gov (United States)

    Sinn, H-P; Helmchen, B; Heil, J; Aulmann, S

    2014-02-01

    The term lobular neoplasia (LN) comprises both atypical lobular hyperplasia (ALH), and lobular carcinoma in situ (LCIS) and thus a spectrum of morphologically heterogeneous but clinically and biologically related lesions. LN is regarded as a nonobligatory precursor lesion of invasive breast cancer and at the same time as an indicator lesion for ipsilateral and contralateral breast cancer risk of the patient. Rare pleomorphic or florid variants of LCIS must be differentiated from classical LCIS. The classical type of invasive lobular carcinoma (ILC) can be distinguished from the non-special type of invasive breast cancer (NST) by E-cadherin inactivation, loss of E-cadherin related cell adhesion and the subsequent discohesive growth pattern. Variant forms of ILC may show different molecular features, and solid and pleomorphic differentiation patterns in cases of high grade variants. Important parameters for the prognostic assessment of ILC are tumor grading and the recognition of morphological variants.

  4. Apoptosis and Tumor Invasion in Breast Cancer

    Science.gov (United States)

    2000-08-01

    while down- regulating the synthesis of at least one inhibitor S~ < of the matrix metalloproteases (TIMP-1) and f / / ,,"* , cystatin C . We are...UNCLASSIFIED AD Award Number: DAMD17-97-1-7268 TITLE: Apoptosis and Tumor Invasion in Breast Cancer PRINCIPAL INVESTIGATOR: Martin Tenniswood, Ph.D...preparing the same or similar computer software, or ( c ) used by a party other than the Government, except that the Government may release or disclose

  5. 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.

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

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    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.

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

    OpenAIRE

    Sobinsky, Justin D.; Willson, Thomas D.; 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...

  8. Preoperative breast MRI in patients with invasive lobular breast cancer

    International Nuclear Information System (INIS)

    Schelfout, K.; Colpaert, C.; Van Goethem, M.; Verslegers, I.; Biltjes, I.; De Schepper, A.; Kersschot, E.; Leyman, P.; Thienpont, L.; Van den Haute, J.; Gillardin, J.P.; Tjalma, W.; Buytaert, Ph.

    2004-01-01

    To investigate the use of MRI in preoperative characterization of invasive lobular breast cancer (ILC) and in detection of multifocal/multicentric disease. We retrospectively reviewed T1-weighted FLASH 3D precontrast and postcontrast MR images together with subtraction images of 26 women with histopathologically proven invasive lobular cancer. Two experienced radiologists described tumor patterns of ILC independently. MR findings of unifocal, multifocal, single quadrant and multiquadrant disease were correlated with results of other imaging techniques and compared with histopathological findings as gold standard. Most ILC presented on MRI as a single spiculated/irregular, inhomogeneous mass (pattern 1, n=12) or as a dominant lesion surrounded by multiple small enhancing foci (pattern 2, n=8). Multiple small enhancing foci with interconnecting enhancing strands (pattern 3) and an architectural distortion (pattern 4) were both described in three cases. There was one case of a focal area of inhomogeneous enhancement (pattern 5) and one normal MR examination (pattern 6). Unifocal and multifocal lesions were identified on MRI in four patients with normal conventional imaging. In nine women, multiple additional lesions or more extensive multiquadrant disease were correctly identified only on MRI. MRI may play an important role in the evaluation of patients with ILC, which is often difficult to diagnose on clinical examination and conventional imaging and more likely occur in multiple sites and in both breasts. However, false-negative MR findings do occur in a small percentage of ILC. (orig.)

  9. Preoperative breast MRI in patients with invasive lobular breast cancer

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    Schelfout, K.; Colpaert, C. [Department of Pathology, University Hospital Antwerp, Wilrijkstraat 10, 2650, Edegem (Belgium); Van Goethem, M.; Verslegers, I.; Biltjes, I.; De Schepper, A. [Department of Radiology, University Hospital Antwerp, Wilrijkstraat 10, 2650, Edegem (Belgium); Kersschot, E.; Leyman, P. [Department of Radiology, O.L.V. Hospital Aalst, Moorselbaan 164, 9000, Aalst (Belgium); Thienpont, L. [Department of Pathology, O.L.V. Hospital Aalst, Moorselbaan 164, 9000, Aalst (Belgium); Van den Haute, J. [Department of Gynecology, O.L.V. Hospital Aalst, Moorselbaan 164, 9000, Aalst (Belgium); Gillardin, J.P. [Department of Surgery, O.L.V. Hospital Aalst, Moorselbaan 164, 9000, Aalst (Belgium); Tjalma, W.; Buytaert, Ph. [Department of Gynecology, University Hospital Antwerp, Wilrijkstraat 10, 2650, Edegem (Belgium)

    2004-07-01

    To investigate the use of MRI in preoperative characterization of invasive lobular breast cancer (ILC) and in detection of multifocal/multicentric disease. We retrospectively reviewed T1-weighted FLASH 3D precontrast and postcontrast MR images together with subtraction images of 26 women with histopathologically proven invasive lobular cancer. Two experienced radiologists described tumor patterns of ILC independently. MR findings of unifocal, multifocal, single quadrant and multiquadrant disease were correlated with results of other imaging techniques and compared with histopathological findings as gold standard. Most ILC presented on MRI as a single spiculated/irregular, inhomogeneous mass (pattern 1, n=12) or as a dominant lesion surrounded by multiple small enhancing foci (pattern 2, n=8). Multiple small enhancing foci with interconnecting enhancing strands (pattern 3) and an architectural distortion (pattern 4) were both described in three cases. There was one case of a focal area of inhomogeneous enhancement (pattern 5) and one normal MR examination (pattern 6). Unifocal and multifocal lesions were identified on MRI in four patients with normal conventional imaging. In nine women, multiple additional lesions or more extensive multiquadrant disease were correctly identified only on MRI. MRI may play an important role in the evaluation of patients with ILC, which is often difficult to diagnose on clinical examination and conventional imaging and more likely occur in multiple sites and in both breasts. However, false-negative MR findings do occur in a small percentage of ILC. (orig.)

  10. Immune Infiltration in Invasive Lobular Breast Cancer.

    Science.gov (United States)

    Desmedt, Christine; Salgado, Roberto; Fornili, Marco; Pruneri, Giancarlo; Van den Eynden, Gert; Zoppoli, Gabriele; Rothé, Françoise; Buisseret, Laurence; Garaud, Soizic; Willard-Gallo, Karen; Brown, David; Bareche, Yacine; Rouas, Ghizlane; Galant, Christine; Bertucci, François; Loi, Sherene; Viale, Giuseppe; Di Leo, Angelo; Green, Andrew R; Ellis, Ian O; Rakha, Emad A; Larsimont, Denis; Biganzoli, Elia; Sotiriou, Christos

    2018-02-20

    Invasive lobular breast cancer (ILC) is the second most common histological subtype of breast cancer after invasive ductal cancer (IDC). Here, we aimed at evaluating the prevalence, levels, and composition of tumor-infiltrating lymphocytes (TILs) and their association with clinico-pathological and outcome variables in ILC, and to compare them with IDC. We considered two patient series with TIL data: a multicentric retrospective series (n = 614) and the BIG 02-98 study (n = 149 ILC and 807 IDC). We compared immune subsets identified by immuno-histochemistry in the ILC (n = 159) and IDC (n = 468) patients from the Nottingham series, as well as the CIBERSORT immune profiling of the ILC (n = 98) and IDC (n = 388) METABRIC and The Cancer Genome Atlas patients. All ILC/IDC comparisons were done in estrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative tumors. All statistical tests were two-sided. TIL levels were statistically significantly lower in ILC compared with IDC (fold-change = 0.79, 95% confidence interval = 0.70 to 0.88, P lobular series, although they did not reach statistical significance in the latter. The Nottingham series revealed that the levels of intratumoral but not total CD8+ were statistically significantly lower in ILC compared with IDC. Comparison of the CIBERSORT profiles highlighted statistically significant differences in terms of immune composition. This study shows differences between the immune infiltrates of ER-positive/HER2-negative ILC and IDC in terms of prevalence, levels, localization, composition, and clinical associations.

  11. 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 cancers. Even though lobular structures are quite infrequent in the male breast, rare cases of invasive lobular breast carcinoma have been described, representing 1-2% of all breast cancers in men. Risk factors include undescended testes, congenital inguinal hernia, orchiectomy, orchitis, testicular injury, infertility and Klinefelter's syndrome, previous thoracic radiotherapy, alterations of the oestrogen-testosterone ratio and familial history (BRCA 2 and 1). The authors present a case of a 52-year-old man with no relevant predisposing factors to breast cancer, who presented with a painless, firm nodule, fixed to the nipple on the left breast, associated with nipple retraction and ulceration, and fully characterised by mammogram and ultrasound. Histopathological and immunohistochemical analysis revealed the diagnosis of invasive lobular breast carcinoma and the patient underwent left radical mastectomy, followed by adjuvant chemotherapy, radiotherapy and hormonotherapy. A brief review of the literature is presented. 2016 BMJ Publishing Group Ltd.

  12. Invasive Cystic Hypersecretory Carcinoma of the Breast: A Case Report

    OpenAIRE

    Lee, Ji Shin; Lee, Young Jik

    2004-01-01

    Cystic hypersecretory lesions of the breast are rare. These breast lesions include cystic hypersecretory hyperplasia (CHH), atypical CHH, and cystic hypersecretory carcinoma (CHC). The characteristic features are dilated ducts and cysts filled with thyroid colloid-like eosinophilic secretion. Only seven cases of invasive CHC have been reported in the literature. Here, we report an additional case of invasive CHC. The histologic features of the tumor showed both micropapillary intraductal carc...

  13. 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

  14. An unusual case of invasive papillary carcinoma of the breast

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    Aysen Terzi

    2012-01-01

    Full Text Available Invasive papillary carcinoma is a rare variant of breast cancer. We report an unusual case of invasive papillary carcinoma of the breast with high nuclear grade, brisk mitosis, necrosis, extensive apocrine differentiation, and intense lymphoplasmacytic infiltrate; additionally triple-negativity for estrogen and progesterone receptors and Her2 neu. The patient underwent modified radical mastectomy and adjuvant chemotherapy. But, it was a node negative breast carcinoma. Increasing the awareness of this clinicopathologic entity would be helpful in avoiding overtreatment of patients with this cancer even if the tumor has negative morphological and immunohistochemical prognosticators.

  15. 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.

  16. 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.

  17. Is axillary sonographic staging less accurate in invasive lobular breast cancer than in ductal breast cancer?

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    Sankaye, Prashant; Chhatani, Sharmila; Porter, Gareth; Steel, Jim; Doyle, Sarah

    2014-10-01

    The purpose of this study was to determine whether axillary sonography is less accurate in invasive lobular breast cancer than in ductal breast cancer. Patients with invasive breast cancer were retrospectively identified from histologic records from 2010 to 2012. Staging axillary sonograms from 96 patients with primary breast cancer in each of 2 subgroups, invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC), were reviewed. Preoperative sonographically guided 14-gauge core biopsy was performed on morphologically abnormal lymph nodes. Thirty-one of 96 patients (32%) in each subgroup were node positive on final postoperative histopathologic analysis. Axillary staging sensitivity was 17 of 31 patients (54%) in the IDC subgroup and 15 of 31(48%) in the ILC subgroup. Further analysis of the data showed no statistically significant differences between these subgroups. We found that there was no statistically significant difference in the accuracy of axillary sonographic staging between ILC and IDC. © 2014 by the American Institute of Ultrasound in Medicine.

  18. Invasive ductal breast cancer metastatic to the sigmoid colon

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    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. Elevated incidence of fractures in women with invasive breast cancer.

    Science.gov (United States)

    Edwards, B J; Gradishar, W J; Smith, M E; Pacheco, J A; Holbrook, J; McKoy, J M; Nardone, B; Tica, S; Godinez-Puig, V; Rademaker, A W; Helenowski, I B; Bunta, A D; Stern, P H; Rosen, S T; West, D P; Guise, T A

    2016-02-01

    This study evaluates the incidence of bone fractures in women with BC.We found that women with invasive breast cancer are at an increased risk for bone fractures, with fractures most commonly occurring at lower extremity and vertebral sites. The risk is further increased in women undergoing cancer therapy. Bone loss and fractures in breast cancer have generally been attributed to aromatase inhibitor use. This study assessed the incidence of fractures after invasive breast cancer diagnosis and evaluated bone density and FRAX risk calculation at time of fracture occurrence. Retrospective cohort study of women with invasive breast cancer [June 2003-December 2011] who participated in an academic hospital based genetic biobank. Demographic and clinical characteristics were abstracted from the electronic medical record (EMR). A total of 422 women with invasive breast cancer were assessed; 79 (28 %) sustained fractures during the observation period; fractures occurred at multiple skeletal sites in 27 cases (116 fractures). The incidence of fractures was 40 per 1000 person-years. Women who sustained fractures were mostly white and had a family history of osteoporosis (36.9 %, p = 0.03) or history of a prior fracture (6/79, p = 0.004). Fractures occurred 4.0 years (range 0-12 years) after cancer diagnosis. Fracture cases had femoral neck bone mineral density (BMD) of 0.72 + 0.12 g/cm(2), T-score of -1.2, that is, within the low bone mass range. Fractures most commonly occurred in lower extremities, vertebral, and wrist sites. Hip fractures accounted for 11 % of fractures, occurring at a median age of 61 years. Fractures occur shortly after commencing cancer therapy. Rapid bone loss associated with cancer therapy may precipitate fractures. Fractures occur at relatively higher BMD in BC. Occurrence of fractures in invasive breast cancer raises the possibility of cancer-induced impairment in bone quality.

  20. Globular adiponectin enhances invasion in human breast cancer cells

    Science.gov (United States)

    FALK LIBBY, EMILY; LIU, JIANZHONG; LI, YI; LEWIS, MONICA J.; DEMARK-WAHNEFRIED, WENDY; HURST, DOUGLAS R.

    2016-01-01

    Every year, a large number of women succumb to metastatic breast cancer due to a lack of curative approaches for this disease. Adiponectin (AdipoQ) is the most abundant of the adipocyte-secreted adipokines. In recent years, there has been an interest in the use of AdipoQ and AdipoQ receptor agonists as therapeutic agents for the treatment of breast cancer. However, while multiple epidemiological studies have previously indicated that low levels of circulating plasma AdipoQ portend poor prognosis in patients with breast cancer, recent studies have reported that elevated expression levels of AdipoQ in breast tissue are correlated with advanced stages of the disease. Thus, the aim of the present study was to clarify the mechanism by which AdipoQ in breast tissue acts directly on tumor cells to regulate the early steps of breast cancer metastasis. In the present study, the effects of different AdipoQ isoforms on the metastatic potential of human breast cancer cells were investigated. The results revealed that globular adiponectin (gAd) promoted invasive cell morphology and significantly increased the migration and invasion abilities of breast cancer cells, whereas full-length adiponectin (fAd) had no effect on these cells. Additionally, gAd, but not fAd, increased the expression levels of microtubule-associated protein 1 light chain 3 beta (LC3B)-II and intracellular LC3B puncta, which are indicators of autophagosome formation, thus suggesting autophagic induction by gAd. Furthermore, the inhibition of autophagic function by autophagy-related protein 7 knockdown attenuated the gAd-induced increase in invasiveness in breast cancer cells. Therefore, the results of the present study suggested that a specific AdipoQ isoform may enhance breast cancer invasion, possibly via autophagic induction. Understanding the roles of the different AdipoQ isoforms as microenvironmental regulatory molecules may aid the development of effective AdipoQ-based treatments for breast cancer

  1. 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.

  2. 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.

  3. Recurrent invasive lobular carcinoma presenting as a ruptured breast implant

    International Nuclear Information System (INIS)

    Botros, Maikel; Chang, Kenneth; Miller, Robert; Krishnan, Sunil; Iott, Matthew

    2011-01-01

    For years, the treatment for invasive lobular carcinoma (ILC) has been mastectomy secondary to the lack of studies investigating the efficacy of breast conservation therapy on patients afflicted with ILC and due to the lack of long-term follow up investigating locoregional recurrence in this patient population. In this article we report the clinical course of a patient diagnosed with ILC. We describe the case of a 50-year-old woman with stage IIB (T2N1M0) ER/PR positive right breast ILC who underwent a right modified radical mastectomy, postoperative chemotherapy, a prophylactic left simple mastectomy with bilateral breast reconstruction and tamoxifen. Approximately 12 years later, she presented with a deflated breast implant and recurrent breast cancer with metastatic spread. She received palliative radiotherapy then palliative chemotherapy. Unfortunately, she succumbed to the cancer less than a year after being diagnosed with metastatic disease. This may be the first case report of a ruptured breast implant presenting at the same time as the diagnosis of recurrent breast cancer

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

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    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.

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

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    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.

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

    International Nuclear Information System (INIS)

    Vermeulen, Jeroen F; Brussel, Aram SA van; Groep, Petra van der; Morsink, Folkert HM; Bult, Peter; Wall, Elsken van der; Diest, Paul J van

    2012-01-01

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

  7. 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.

  8. Transcriptomic and genomic features of invasive lobular breast cancer.

    Science.gov (United States)

    Desmedt, Christine; Zoppoli, Gabriele; Sotiriou, Christos; Salgado, Roberto

    2017-06-01

    Accounting for 10-15% of all breast neoplasms, invasive lobular breast cancer (ILC) is the second most common histological subtype of breast cancer after invasive ductal breast cancer (IDC). Understanding ILC biology, which differs from IDC in terms of clinical presentation, treatment response, relapse timing and patterns, is essential in order to adopt novel, disease-specific management strategies. While the contribution of the histological subtypes to tumour biology has been poorly investigated and acknowledged in the past, recently several major, independent efforts have led to the assembly and molecular characterization of well-annotated ILC case sets. In this review, we provide a critical overview of the literature exploring ILC, through comprehensive and multiomic methods. The first part specifically focuses on ILC transcriptomic features by reviewing the intrinsic molecular subtypes, the application of gene expression scores for the prediction of recurrence, and the identification of gene expression subtypes. The second part describes the main research efforts that lead to the identification of the genomic landscape of ILC, with a special focus to findings that differentiate ILC from IDC and carry potential clinical relevance. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. 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.

  10. Conservative treatment for invasive lobular carcinoma of the breast

    International Nuclear Information System (INIS)

    Dilhuydy, Jean-Marie; Salem, Naji; Durand, Michel; Prie, Loiec; Stoeckle, Eberhard; Benyoucef, Ahmed; Dilhuydy, Marie-Helene

    1997-01-01

    Purpose/Objective: To evaluate the place of conservative treatment in invasive lobular carcinoma. Materials and Methods: From 01/01/85 to 31/12/92, 109 patients with clinically and mammographically unifocal invasive lobular carcinoma of the breast (T<35 mm) underwent tumorectomy, axillary dissection and radiation therapy; they received an adjuvant treatment in case of nodal involvement (n = 31) or lack of estrogen and progesterone receptors (n = 16). The entire breast received 50 Gy with a systematic boost of 10 Gy. Results: With a median follow-up of 86 months, we observed 11 isolated local recurrences (T0 = (3(19)), T1 = (6(41)), T2 = (2(49))), 7 local recurrences associated with metastases (T1 = (3(41)), T2 = (4(49))) and 7 cases of metastatic diseases (T1 = (4(41)), T2 = (3(49))). Among the 11 patients with isolated local recurrence, 7 are alive with no evidence of disease after salvage mastectomy. Nine contro-lateral breast cancers occurred, 2 synchronous and 7 metachronous. The 5-year actuarial local relapse free survival, metastase free survival and overall survival are respectively 87.3%, 89.5% and 92.5%, whatever histological subtypes. These results are comparable to those obtained in 1393 cases of infiltrating ductal carcinoma similarly treated during the same period in our institute, except for local relapse (87.3% vs 91%, p = 0.008). Conclusion: Conservative treatment for invasive lobular carcinoma of the breast (T<35 mm) is appropriate in the absence of clinical or mammographic multifocality

  11. Investigating Mechanisms of Alkalinization for Reducing Primary Breast Tumor Invasion

    Directory of Open Access Journals (Sweden)

    Ian F. Robey

    2013-01-01

    Full Text Available The extracellular pH (pHe of many solid tumors is acidic as a result of glycolytic metabolism and poor perfusion. Acidity promotes invasion and enhances metastatic potential. Tumor acidity can be buffered by systemic administration of an alkaline agent such as sodium bicarbonate. Tumor-bearing mice maintained on sodium bicarbonate drinking water exhibit fewer metastases and survive longer than untreated controls. We predict this effect is due to inhibition of tumor invasion. Reducing tumor invasion should result in fewer circulating tumor cells (CTCs. We report that bicarbonate-treated MDA-MB-231 tumor-bearing mice exhibited significantly lower numbers of CTCs than untreated mice (. Tumor pHe buffering may reduce optimal conditions for enzymes involved in tumor invasion such as cathepsins and matrix metalloproteases (MMPs. To address this, we tested the effect of transient alkalinization on cathepsin and MMP activity using enzyme activatable fluorescence agents in mice bearing MDA-MB-231 mammary xenografts. Transient alkalinization significantly reduced the fluorescent signal of protease-specific activatable agents in vivo (. Alkalinization, however, did not affect expression of carbonic anhydrase IX (CAIX. The findings suggest a possible mechanism in a live model system for breast cancer where systemic alkalinization slows the rate of invasion.

  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, Kristin; 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

    2015-10-08

    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. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Histology and Immunophenotype of Invasive Lobular Breast Cancer. Daily Practice and Pitfalls

    OpenAIRE

    Varga, Z; Mallon, E

    2009-01-01

    Invasive lobular carcinomas (ILC) represent the most common subtype of invasive breast cancer and account for about 5-15% of all breast cancer cases. Invasive lobular carcinoma is often accompanied by in situ lesions, by lobular neoplasia (LN). Invasive lobular carcinomas display diverse histologic patterns varying from classical through solid to pleomorphic subtypes. When analyzing histological subtypes, the classical variant is reported to have a more favorable outcome. The majority of inva...

  14. 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.

  15. Occult Invasive Lobular Carcinoma of Breast Detected by Stomach Metastasis: A Case Report

    International Nuclear Information System (INIS)

    KIm, So Jung; Jung, Hae Kyoung; Ko, Kyung Hee; Yoon, Jung Hyun

    2012-01-01

    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. Usefulness of three dimensional MRI for invasive breast cancer

    International Nuclear Information System (INIS)

    Nakada, Yutaka; Kakizaki, Dai; Kurata, Chishio; Akata, Soichi; Tokuuye, Koichi; Araki, Youchi; Katsuyama, Katsuhiro; Sasaki, Kazuhiro

    2011-01-01

    The first step in the therapeutic plan for breast cancer is to determine the presence and location of the lesion. In a significant number of cases, however, the lesion is difficult to detect, even using various diagnostic imaging modalities. MRI is therefore highly anticipated as a modality for breast cancer detection. In this study we evaluated the diagnostic efficacy of dynamic imaging and 3D imaging with high-resolution MRI in 236 cases of papillo-tubular carcinoma, solid-tubular carcinoma and scirrhous carcinoma: the 3 most common histological types of invasive ductal cancer. The cases were examined by fat-saturated T1/T2-weighted and dynamic MRI imaging, and 3D images were generated for comparison. Breast cancer lesions were detected in 100% of the 3D images obtained by dynamic imaging using contrast media and equilibrium phase, versus 12.2% and 31.4% of the T1- and T2-weighted images, respectively. These results show that 3D imaging is highly useful for detecting the presence of breast cancer. Similar methods are expected to be applied for stereoscopic imaging of tumors and lymph nodes, as well as for surgical simulation. (author)

  17. 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.)

  18. Interventional MRI of the breast: minimally invasive therapy

    International Nuclear Information System (INIS)

    Hall-Craggs, M.A.

    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.)

  19. Invasive Carcinoma of Breast with Adnexal Differentiation of Trichoblastic Type

    Directory of Open Access Journals (Sweden)

    Sarala Ravindran

    2016-06-01

    Full Text Available We present a rare distinctive variant of invasive carcinoma of breast characterized by adnexal differentiation of tumor of trichoblastic type. The neoplasm was identified in a mastectomy specimen from an 83-year-old Chinese woman. Morphologically, the trichoblastic differentiation was characterized by the formation of solid sheets and nests of basaloid cells. The tumor cells were positive for cytokeratin 5/6, BER-EP4, bcl-2, and beta-catenin. Stromal cells were positive for CD10. The tumor cells exhibited a and ldquo;triple negative and rdquo; profile; the nuclei did not react with antibodies to estrogen and progesterone receptors but failed to show overexpression of the HER2/neu protein. The MIB-1 labeling index averaged 20%. It is hoped that this case increases awareness for this unique morphological variant of invasive ductal carcinoma. [J Interdiscipl Histopathol 2016; 4(2.000: 48-51

  20. [An analysis of 68 invasive lobular breast cancer cases in clinicopathological characteristics and the prognostic determinants].

    Science.gov (United States)

    Liu, Q; Xiang, H Y; Ye, J M; Xu, L; Zhang, H; Zhang, S; Duan, X N; Liu, Y H

    2018-02-01

    Objective: To study the clinicopathological characteristics and the prognostic determinants of the invasive lobular carcinoma breast cancer. Methods: This was a retrospective single-center study of invasive lobular breast cancer cases diagnosed from January 2008 to December 2014 at Peking University First Hospital Breast Disease Center. The study enrolled 68 invasive lobular breast cancer patients, which represented 3.64% (68/1 870) of total invasive breast cancer. The median age of all selected patients was 46 years ranging from 36 to 83 years. All patients were restaged based on the 8(th) edition of AJCC cancer staging system and follow-up data including disease-free survival (DFS) and overall survival (OS) were analyzed to explore the prognostic determinants. The 5-year OS and DFS were calculated using Kaplan-Meier method; the significance of correlations between clinicopathological features and prognostic factors was estimated using log-rank test. Results: There were significant differences in OS between patients with different anatomic stage, prognostic stage, lymph node metastasis, progesterone receptor (PR) expression, lymphvascular invasion and perineural invasion (χ(2:) 4.318 to 32.394, all P invasion (χ(2:) 4.347 to 27.369, all P invasion are the prognostic factors of invasive lobular breast cancer. Regard to invasive lobular breast cancer patients, clinicians should pay close attention to the differences between prognostic stage and anatomic stage.

  1. Effect of adjuvant chemotherapy in postmenopausal patients with invasive ductal versus lobular breast cancer

    NARCIS (Netherlands)

    Truin, W.; Voogd, A.C.; Vreugdenhil, G.; van der Heiden-van der Loo, M.; Siesling, Sabine; Roumen, R.M.

    2012-01-01

    Background On the basis of the lack of response of invasive lobular breast cancer to neoadjuvant chemotherapy, we questioned the effectiveness of adjuvant chemotherapy in relation to histology. Patients and methods Women with primary nonmetastatic invasive ductal or (mixed type) lobular breast

  2. 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.

  3. [Second operation more frequent following breast-conserving treatment for invasive lobular than for invasive non-lobular carcinoma

    NARCIS (Netherlands)

    Zeeuw, S. de; Wildenberg, F.; Strobbe, L.; Wobbes, T.

    2009-01-01

    OBJECTIVE: To establish the frequency of re-excision or mastectomy in women who had breast-conserving treatment for invasive lobular mammary carcinoma. DESIGN: Retrospective. METHOD: Data on the number of patients with invasive carcinoma from 1998-2006 were obtained from the national pathology

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

    Science.gov (United States)

    2003-05-01

    IMMUNOHISTOCHEMICAL ASSESSMENT OF \\ Breast Disease PRIMARY LESIONS OF BREAST EPITHELIAL February 13-16, 2003 INVASION INTO BLOOD VESSELS Ritz - Carlton , Amelia...myoepithelial cell lineages: A new cell biological concept . Lab Invest 2002;82(6):737-46. 2. Tavassoli FA. Pathology of the Breast, 2nd edn. Hong Kong: McGraw

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

    Energy Technology Data Exchange (ETDEWEB)

    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.)

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

    Directory of Open Access Journals (Sweden)

    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.

  7. Outcome of invasive lobular carcinoma of breast in Malaysia

    Directory of Open Access Journals (Sweden)

    Kamudin Nur Allaiyna Ferdaus

    2017-12-01

    Full Text Available Background: Breast cancer is the commonest cancer and 2nd most common cause of cancer death among women worldwide. Histologically breast cancer can be divided into Invasive Lobular Carcinoma (ILC, Invasive Ductal Carcinoma (IDC and others. ILC has its own unique patient’s demographic, histological appearance, imaging characteristics and clinical outcome. Previous published study has shown that ILC has better overall survival compared to IDC. Sadly, despite being so common, there is still lack of study comparing ILC and IDC in Malaysia setting. Methods: 5225 of patients diagnosed with ILC and IDC were managed in University Malaya Medical Center within 1993 to 2013 has been included in this study. Chi square test were performed to determine the demographic and clinical factors associated with ILC and IDC. Kaplen-Meier method was used to obtain overall survival of these patients. Through a Cox regression analysis, mortality in patients diagnosed with ILC and IDC were identified, by adjusting the possible confounding factors. Results: ILC is more common in elderly compared to younger patients. There is no association between ethnicity and types of invasive carcinoma. Patients with ILC were more likely to have lymph nodes involvement (p = 0.001, estrogen receptor positive (p = 0.001, absent of lymphovascular invasion (p = 0.028, mastectomy (p = 0.022 and hormonal therapy (p = 0.002 compared to IDC and it is statistically significant. Nevertheless, survival was not significantly different between ILC and IDC; 5-year OS; 77.4% (95% CI 77.34 to 77.46 and 71.3% (95% CI 71.29 to 71.30, respectively; the 10 year OS; 52.2% (95% CI 52.13 to 52.27 and 49.7% (95% CI 49.68 to 49.72, respectively. The adjusted hazard ratio comparing ILC and IDC using Cox regression was 1.21 (0.85 to 1.72 showing there is no significant difference between patients presented with ILC and IDC in terms of survival. Conclusion: Based on Malaysian data gathered from University

  8. The urokinase-system in tumor tissue stroma of the breast and breast cancer cell invasion.

    Science.gov (United States)

    Hildenbrand, Ralf; Schaaf, Antonela

    2009-01-01

    The urokinase-system has been implicated in tumor spread. The serine protease urokinase-type plasminogen activator (uPA), its receptor (uPAR) and its inhibitor (PAI-1) are involved in the control of extracellular turnover, cell migration, invasion, cell signalling, proliferation, apoptosis and angiogenesis leading to a variety of different responses, under both physiological and pathological conditions. uPA and PAI-1 were the first novel tumor biological factors to be validated at the highest level of evidence regarding their clinical utility in breast cancer. However, it is unclear whether it is their (relative) levels in the tumor stroma or in the tumor cells themselves that is the most relevant to patients outcome. This is the first study in which tumor cells and stromal tissue of invasive breast carcinomas were separated by laser capture microdissection followed by ELISA-based determination of the uPA, uPAR and PAI-1 levels. In addition, we localized uPA, uPAR and PAI-1 distribution in invasive breast cancer (n=30) and in ductal carcinoma in situ (DCIS, n=30) by immunohistochemistry and in situ hybridization. We have demonstrated that no significant differences between uPA, uPAR and PAI-1 levels in tumor stroma only, tumor cells only and not separated breast cancer tissue exist (p>0.05). Our results suggest that similar expression levels of these factors in both compartments and in not separated breast cancer tissue may have the same impact on the clinical behavior of breast cancer. These results are an important issue for practical use of tissue sampling. For using uPA and PAI-1 levels as prognostic and predictive factors in breast cancer the quantity of tumor stroma in the tumor tissue specimen is not relevant for assessment patients outcome. Our results were confirmed by immunohistochemistry and in situ hybridization analysis showing that in nearly all cases of invasive carcinomas and DCIS fibroblasts as well as macrophages strongly express uPA, uPAR and PAI

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

    International Nuclear Information System (INIS)

    Sedlmayer, F.

    2013-01-01

    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 research lies in partial breast

  10. 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

  11. Genomic Characterization of Primary Invasive Lobular Breast Cancer.

    Science.gov (United States)

    Desmedt, Christine; Zoppoli, Gabriele; Gundem, Gunes; Pruneri, Giancarlo; Larsimont, Denis; Fornili, Marco; Fumagalli, Debora; Brown, David; Rothé, Françoise; Vincent, Delphine; Kheddoumi, Naima; Rouas, Ghizlane; Majjaj, Samira; Brohée, Sylvain; Van Loo, Peter; Maisonneuve, Patrick; Salgado, Roberto; Van Brussel, Thomas; Lambrechts, Diether; Bose, Ron; Metzger, Otto; Galant, Christine; Bertucci, François; Piccart-Gebhart, Martine; Viale, Giuseppe; Biganzoli, Elia; Campbell, Peter J; Sotiriou, Christos

    2016-06-01

    Invasive lobular breast cancer (ILBC) is the second most common histologic subtype after invasive ductal breast cancer (IDBC). Despite clinical and pathologic differences, ILBC is still treated as IDBC. We aimed to identify genomic alterations in ILBC with potential clinical implications. From an initial 630 ILBC primary tumors, we interrogated oncogenic substitutions and insertions and deletions of 360 cancer genes and genome-wide copy number aberrations in 413 and 170 ILBC samples, respectively, and correlated those findings with clinicopathologic and outcome features. Besides the high mutation frequency of CDH1 in 65% of tumors, alterations in one of the three key genes of the phosphatidylinositol 3-kinase pathway, PIK3CA, PTEN, and AKT1, were present in more than one-half of the cases. HER2 and HER3 were mutated in 5.1% and 3.6% of the tumors, with most of these mutations having a proven role in activating the human epidermal growth factor receptor/ERBB pathway. Mutations in FOXA1 and ESR1 copy number gains were detected in 9% and 25% of the samples. All these alterations were more frequent in ILBC than in IDBC. The histologic diversity of ILBC was associated with specific alterations, such as enrichment for HER2 mutations in the mixed, nonclassic, and ESR1 gains in the solid subtype. Survival analyses revealed that chromosome 1q and 11p gains showed independent prognostic value in ILBC and that HER2 and AKT1 mutations were associated with increased risk of early relapse. This study demonstrates that we can now begin to individualize the treatment of ILBC, with HER2, HER3, and AKT1 mutations representing high-prevalence therapeutic targets and FOXA1 mutations and ESR1 gains deserving urgent dedicated clinical investigation, especially in the context of endocrine treatment. © 2016 by American Society of Clinical Oncology.

  12. Invasive ductal carcinoma with lobular features: a comparison study to invasive ductal and invasive lobular carcinomas of the breast.

    Science.gov (United States)

    Arps, David P; Healy, Patrick; Zhao, Lili; Kleer, Celina G; Pang, Judy C

    2013-04-01

    Invasive ductal carcinoma with lobular features (IDC-L) is not recognized as a distinct subtype of breast cancer, and its clinicopathologic features and outcomes are unknown. In this retrospective study, we focused on characterization of clinicopathologic features and outcomes of IDC-L and compared them to invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC). 183 cases of IDC-L from 1996 to 2011 were compared with 1,499 cases of IDC and 375 cases of ILC. Available slides of IDC-L (n = 150) were reviewed to quantify the lobular component (≤ 20, 21-50, 51-80, >80 %), defined as small cells individually dispersed, arranged in linear cords, or in loose aggregates without the formation of tubules or cohesive nests. E-cadherin immunostain was performed to confirm ductal origin. Compared to IDC, IDC-L was more likely to have lower histologic grade (p lobular component in IDC-L had no impact on the size, nodal status, stage, or outcome. Our data suggest that although IDC-L may be a variant of IDC, with >90 % of cases being E-cadherin positive, the clinical and biological characteristics are more similar to that of ILC.

  13. [Epithelial cadherins and associated molecules in invasive lobular breast cancer].

    Science.gov (United States)

    Brilliant, Yu M; Brilliant, A A; Sazonov, S V

    to estimate the expression of cell adhesion molecules E- and P-cadherin, as well as that of cadherin-catenin complexes in invasive lobular breast cancer (BC) cells. 250 cases of postoperative material from patients diagnosed with invasive lobular BC were studied. The expressions of cell adhesion molecules E-cadherin, P-cadherin, β-catenin, p120 catenin, and vimentin were determined by immunohistochemical assay in all cases. The examined cases were divided into molecular biological subtypes, based on the evaluation of estrogen receptors (ER), progesterone receptors (PR), HER-2/neu, and Ki-67 proliferative index. The membrane expression of E-cadherin on the tumor cells was found to be preserved in 93%; the cytoplasmic expression of β-catenin and p120-catenin appeared in 60 and 72% of cases, respectively. The expression of P-cadherin was detected in 82% of cases. The coexpression of E- and P-cadherin was noted in 90% of all the examined cases. There was a correlation between the expression of E- and P-cadherins (V=0.34; pcancer and its metastasis.

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

    International Nuclear Information System (INIS)

    Souchon, R.; Sautter-Bihl, M.L.; Sedlmayer, F.; Budach, W.; Dunst, J.; Feyer, P.; Fietkau, R.; Sauer, R.; Harms, W.; Wenz, F.; Haase, W.

    2014-01-01

    To complement and update the 2007 practice guidelines of the breast cancer expert panel of the German Society of Radiation Oncology (DEGRO) for radiotherapy (RT) of breast cancer. Owing to its growing clinical relevance, in the current version, a separate paper is dedicated to non-invasive proliferating epithelial neoplasia of the breast. In addition to the more general statements of the German interdisciplinary S3 guidelines, this paper is especially focused on indication and technique of RT in addition to breast conserving surgery. The DEGRO expert panel performed a comprehensive survey of the literature comprising recently published data from clinical controlled trials, systematic reviews as well as meta-analyses, referring to the criteria of evidence-based medicine yielding new aspects compared to 2005 and 2007. The literature search encompassed the period 2008 to September 2012 using databases of PubMed and Guidelines International Network (G-I-N). Search terms were ''non invasive breast cancer'', ''ductal carcinoma in situ, ''dcis'', ''borderline breast lesions'', ''lobular neoplasia'', ''radiotherapy'' and ''radiation therapy''. In addition to the more general statements of the German interdisciplinary S3 guidelines, this paper is especially focused on indications of RT and decision making of non-invasive neoplasia of the breast after surgery, especially ductal carcinoma in situ. Among different non-invasive neoplasia of the breast only the subgroup of pure ductal carcinoma in situ (DCIS; synonym ductal intraepithelial neoplasia, DIN) is considered for further recurrence risk reduction treatment modalities after complete excision of DCIS, particularly RT following breast conserving surgery (BCS), in order to avoid a mastectomy. About half of recurrences are invasive cancers. Up to 50?% of all recurrences require salvage mastectomy. Randomized clinical trials and a huge number of mostly observational studies have unanimously demonstrated that RT significantly

  15. Effects of omega-3 fatty acids on progestin stimulation of invasive properties in breast cancer.

    Science.gov (United States)

    Moore, Michael R; King, Rebecca A

    2012-12-01

    Clinical studies have shown that progestins increase breast cancer risk in hormone replacement therapy, while we and others have previously reported that progestins stimulate invasive properties in progesterone receptor (PR)-rich human breast cancer cell lines. Based on others' reports that omega-3 fatty acids inhibit metastatic properties of breast cancer, we have reviewed the literature for possible connections between omega-3 fatty-acid-driven pathways and progestin-stimulated pathways in an attempt to suggest theoretical mechanisms for possible omega-3 fatty acid inhibition of progestin stimulation of breast cancer invasion. We also present some data suggesting that fatty acids regulate progestin stimulation of invasive properties in PR-rich T47D human breast cancer cells, and that an appropriate concentration of the omega-3 fatty acid eicosapentaenoic acid inhibits progestin stimulation of invasive properties. It is hoped that focus on the inter-relationship between pathways by which omega-3 fatty acids inhibit and progestins stimulate breast cancer invasive properties will lead to further in vitro, in vivo, and clinical studies testing the hypothesis that omega-3 fatty acids can inhibit progestin stimulation of invasive properties in breast cancer, and ameliorate harmful effects of progestins which occur in combined progestin-estrogen hormone replacement therapy.

  16. Outcomes After Breast Conservation Treatment With Radiation in Women With Prior Nonbreast Malignancy and Subsequent Invasive Breast Carcinoma

    International Nuclear Information System (INIS)

    Nemani, Deepika; Vapiwala, Neha; Hwang, W.-T.; Solin, Lawrence J.

    2009-01-01

    Purpose: Little information has been reported regarding outcomes after treatment for patients with early-stage invasive breast cancer and a prior nonbreast malignancy. This report analyzes the outcomes in patients with Stage I and II breast cancer after breast conservation treatment (BCT) with a prior nonbreast malignancy. Methods and Materials: The study cohort comprised 66 women with invasive breast cancer and a prior nonbreast malignancy. All patients were treated with breast conservation surgery followed by definitive breast irradiation between 1978 and 2003. Median ages at diagnosis of invasive breast cancer and prior malignancy were 57 and 50 years, respectively. The median interval between the prior malignancy and breast cancer was 7.0 years. Median and mean follow-up times after BCT were 5.3 and 7.0 years. Results: The 5-year and 10-year overall survival rates were 94% (95% confidence interval [CI], 82-98%) and 78% (95% CI, 59-89%), respectively. There were 4 patients (6%) with local failure and 10 patients (15%) with distant metastases. The 10-year rate of local failure rate was 5% (95% CI, 2-16%) and freedom from distant metastases was 78% (95% CI, 61-88%). No obvious differences in survival or local control were noted compared with the reported results in the literature for patients with invasive breast cancer alone. Conclusions: Both overall survival and local control at 5 and 10 years were comparable to rates observed in early-stage breast cancer patients without a prior malignancy. Prior nonbreast malignancy is not a contraindication to BCT, if the primary cancer is effectively controlled

  17. Total RNA Sequencing Analysis of DCIS Progressing to Invasive Breast Cancer

    Science.gov (United States)

    2015-09-01

    Assay Kits respectively on the Qubit 2.0 Fluorometer (Life Technologies). The BioRad Experion Automated Electrophoresis System RNA kit was used to...AWARD NUMBER: W81XWH-14-1-0080 TITLE: Total RNA Sequencing Analysis of DCIS Progressing to Invasive Breast Cancer. PRINCIPAL INVESTIGATOR...Aug 2015 4. TITLE AND SUBTITLE Total RNA Sequencing Analysis of DCIS Progressing to Invasive Breast Cancer. 5a. CONTRACT NUMBER 5b. GRANT

  18. Microvesicles secreted by macrophages shuttle invasion-potentiating microRNAs into breast cancer cells

    Directory of Open Access Journals (Sweden)

    Lin Ling

    2011-09-01

    Full Text Available Abstract Background Tumor-associated macrophages (TAMs are alternatively activated cells induced by interleukin-4 (IL-4-releasing CD4+ T cells. TAMs promote breast cancer invasion and metastasis; however, the mechanisms underlying these interactions between macrophages and tumor cells that lead to cancer metastasis remain elusive. Previous studies have found microRNAs (miRNAs circulating in the peripheral blood and have identified microvesicles, or exosomes, as mediators of cell-cell communication. Therefore, one alternative mechanism for the promotion of breast cancer cell invasion by TAMs may be through macrophage-secreted exosomes, which would deliver invasion-potentiating miRNAs to breast cancer cells. Results We utilized a co-culture system with IL-4-activated macrophages and breast cancer cells to verify that miRNAs are transported from macrophages to breast cancer cells. The shuttling of fluorescently-labeled exogenous miRNAs from IL-4-activated macrophages to co-cultivated breast cancer cells without direct cell-cell contact was observed. miR-223, a miRNA specific for IL-4-activated macrophages, was detected within the exosomes released by macrophages and was significantly elevated in the co-cultivated SKBR3 and MDA-MB-231 cells. The invasiveness of the co-cultivated breast cancer cells decreased when the IL-4-activated macrophages were treated with a miR-223 antisense oligonucleotide (ASO that would inhibit miR-223 expression. Furthermore, results from a functional assay revealed that miR-223 promoted the invasion of breast cancer cells via the Mef2c-β-catenin pathway. Conclusions We conclude that macrophages regulate the invasiveness of breast cancer cells through exosome-mediated delivery of oncogenic miRNAs. Our data provide insight into the mechanisms underlying the metastasis-promoting interactions between macrophages and breast cancer cells.

  19. Microvesicles secreted by macrophages shuttle invasion-potentiating microRNAs into breast cancer cells

    Science.gov (United States)

    2011-01-01

    Background Tumor-associated macrophages (TAMs) are alternatively activated cells induced by interleukin-4 (IL-4)-releasing CD4+ T cells. TAMs promote breast cancer invasion and metastasis; however, the mechanisms underlying these interactions between macrophages and tumor cells that lead to cancer metastasis remain elusive. Previous studies have found microRNAs (miRNAs) circulating in the peripheral blood and have identified microvesicles, or exosomes, as mediators of cell-cell communication. Therefore, one alternative mechanism for the promotion of breast cancer cell invasion by TAMs may be through macrophage-secreted exosomes, which would deliver invasion-potentiating miRNAs to breast cancer cells. Results We utilized a co-culture system with IL-4-activated macrophages and breast cancer cells to verify that miRNAs are transported from macrophages to breast cancer cells. The shuttling of fluorescently-labeled exogenous miRNAs from IL-4-activated macrophages to co-cultivated breast cancer cells without direct cell-cell contact was observed. miR-223, a miRNA specific for IL-4-activated macrophages, was detected within the exosomes released by macrophages and was significantly elevated in the co-cultivated SKBR3 and MDA-MB-231 cells. The invasiveness of the co-cultivated breast cancer cells decreased when the IL-4-activated macrophages were treated with a miR-223 antisense oligonucleotide (ASO) that would inhibit miR-223 expression. Furthermore, results from a functional assay revealed that miR-223 promoted the invasion of breast cancer cells via the Mef2c-β-catenin pathway. Conclusions We conclude that macrophages regulate the invasiveness of breast cancer cells through exosome-mediated delivery of oncogenic miRNAs. Our data provide insight into the mechanisms underlying the metastasis-promoting interactions between macrophages and breast cancer cells. PMID:21939504

  20. 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 cancer treatment for a large proportion of patients with breast cancer. Cancer 2017;123:3015-21. © 2017 American Cancer Society. © 2017 American Cancer Society.

  1. Alcohol promotes breast cancer cell invasion by regulating the Nm23-ITGA5 pathway

    Directory of Open Access Journals (Sweden)

    Poh Karen

    2011-08-01

    Full Text Available Abstract Background Alcohol consumption is an established risk factor for breast cancer metastasis. Yet, the mechanism by which alcohol promotes breast cancer metastases is unknown. The ability of cancer cells to invade through tissue barriers (such as basement membrane and interstitial stroma is an essential step towards establishing cancer metastasis. In the present study, we identify and examine the roles of two genes, Nm23 and ITGA5, in alcohol-induced breast cancer cell invasion. Methods Human breast cancer T47D cells were treated with ethanol at various concentrations. Boyden chamber invasion assays were used to measure cellular invasive ability. The mRNA expression level of metastasis suppressor genes including Nm23 was determined by qRT-PCR. ITGA5 was identified using a qRT-PCR array of 84 genes important for cell-cell and cell-extracellular matrix interactions. Nm23 overexpression in addition to Nm23- and ITGA5 knock-down were used to determine the role of the Nm23-ITGA5 pathway on cellular invasive ability of T47D cells. Protein expression levels were verified by Western blot. Results Alcohol increased the invasive ability of human breast cancer T47D cells in a dose-dependent manner through the suppression of the Nm23 metastatic suppressor gene. In turn, Nm23 down-regulation increased expression of fibronectin receptor subunit ITGA5, which subsequently led to increased cellular invasion. Moreover, Nm23 overexpression was effective in suppressing the effects of alcohol on cell invasion. In addition, we show that the effects of alcohol on invasion were also inhibited by knock-down of ITGA5. Conclusions Our results suggest that the Nm23-ITGA5 pathway plays a critical role in alcohol-induced breast cancer cell invasion. Thus, regulation of this pathway may potentially be used to prevent the establishment of alcohol-promoted metastases in human breast cancers.

  2. Five-Year Risk of Interval-Invasive Second Breast Cancer

    Science.gov (United States)

    Buist, Diana S. M.; Houssami, Nehmat; Dowling, Emily C.; Halpern, Elkan F.; Gazelle, G. Scott; Lehman, Constance D.; Henderson, Louise M.; Hubbard, Rebecca A.

    2015-01-01

    Background: Earlier detection of second breast cancers after primary breast cancer (PBC) treatment improves survival, yet mammography is less accurate in women with prior breast cancer. The purpose of this study was to examine women presenting clinically with second breast cancers after negative surveillance mammography (interval cancers), and to estimate the five-year risk of interval-invasive second cancers for women with varying risk profiles. Methods: We evaluated a prospective cohort of 15 114 women with 47 717 surveillance mammograms diagnosed with stage 0-II unilateral PBC from 1996 through 2008 at facilities in the Breast Cancer Surveillance Consortium. We used discrete time survival models to estimate the association between odds of an interval-invasive second breast cancer and candidate predictors, including demographic, PBC, and imaging characteristics. All statistical tests were two-sided. Results: The cumulative incidence of second breast cancers after five years was 54.4 per 1000 women, with 325 surveillance-detected and 138 interval-invasive second breast cancers. The five-year risk of interval-invasive second cancer for women with referent category characteristics was 0.60%. For women with the most and least favorable profiles, the five-year risk ranged from 0.07% to 6.11%. Multivariable modeling identified grade II PBC (odds ratio [OR] = 1.95, 95% confidence interval [CI] = 1.15 to 3.31), treatment with lumpectomy without radiation (OR = 3.27, 95% CI = 1.91 to 5.62), interval PBC presentation (OR = 2.01, 95% CI 1.28 to 3.16), and heterogeneously dense breasts on mammography (OR = 1.54, 95% CI = 1.01 to 2.36) as independent predictors of interval-invasive second breast cancers. Conclusions: PBC diagnosis and treatment characteristics contribute to variation in subsequent-interval second breast cancer risk. Consideration of these factors may be useful in developing tailored post-treatment imaging surveillance plans. PMID:25904721

  3. Managing the risk of invasive breast cancer in women at risk for breast cancer and osteoporosis: the role of raloxifene

    Directory of Open Access Journals (Sweden)

    Victor G Vogel

    2008-12-01

    Full Text Available Victor G VogelThe University of Pittsburgh Cancer Institute, Magee-Womens Hospital, Pittsburgh, PA, USAAbstract: Raloxifene hydrochloride is a selective estrogen receptor modulator (SERM that has antiestrogenic effects on breast and endometrial tissue and estrogenic effects on bone, lipid metabolism, and blood clotting. Raloxifene significantly improves serum lipids and serum markers of cardiovascular disease risk, but it has no significant effect on the risk of primary coronary events. A meta-analysis of randomized, double-blind, placebo-controlled trials of raloxifene for osteoporosis showed the odds of fracture risk were 0.60 (95% confidence interval [CI] = 0.49–0.74 for raloxifene 60 mg/day compared with placebo. During 8 years of follow-up in an osteoporosis trial, the raloxifene group had a 76% reduction in the incidence of invasive ER-positive breast cancer compared with the placebo group. In the STAR trial, the incidence of invasive breast cancer was 4.30 per 1000 women-years with raloxifene and 4.41 per 1000 with tamoxifen; RR = 1.02; 95% CI, 0.82–1.28. The effect of raloxifene on invasive breast cancer was, therefore, equivalent to that of tamoxifen with more favorable rates of adverse effects including uterine malignancy and clotting events. Millions of postmenopausal women could derive net benefit from raloxifene through reduced rates of fracture and invasive breast cancer.Keywords: raloxifene, osteoporosis, breast cancer risk reduction

  4. The effectiveness of MR imaging in the assessment of invasive lobular carcinoma of the breast.

    NARCIS (Netherlands)

    Mann, R.M.

    2010-01-01

    Invasive lobular carcinoma (ILC) of the breast is, due to its diffuse infiltrative growth pattern, a diagnostic challenge. Even in retrospect, only up to 80% are visible at mammography. Moreover, both mammography and ultrasound tend to structurally underestimate the size of ILC. Breast magnetic

  5. Abdominal Wall Metastasis from an Invasive Lobular Carcinoma of the Breast: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hana; Son, Eun Ju; Youk, Ji Hyun; Chung, Jin [Dept. of Radiology, Gangnam Severance Hospital, Yensei University College of Medicine, Seoul (Korea, Republic of); Noh, Song Mi; Jung, Woo Hee [Dept. of Diagnostic Pathology, Gangnam Severance Hospital, Yensei University College of Medicine, Seoul (Korea, Republic of)

    2011-06-15

    Breast cancer is one of the most common malignancies in women. Breast cancer frequently metastasizes to the bones, lungs, and liver. However, the recurrence of distant soft-tissue metastasis except to the chest wall is extremely rare. Here, we describe our experience with a patient in whom invasive lobular carcinoma of the breast with metastasis to the abdominal wall presented as subcutaneous nodules without local recurrence.

  6. Abdominal Wall Metastasis from an Invasive Lobular Carcinoma of the Breast: A Case Report

    International Nuclear Information System (INIS)

    Kim, Hana; Son, Eun Ju; Youk, Ji Hyun; Chung, Jin; Noh, Song Mi; Jung, Woo Hee

    2011-01-01

    Breast cancer is one of the most common malignancies in women. Breast cancer frequently metastasizes to the bones, lungs, and liver. However, the recurrence of distant soft-tissue metastasis except to the chest wall is extremely rare. Here, we describe our experience with a patient in whom invasive lobular carcinoma of the breast with metastasis to the abdominal wall presented as subcutaneous nodules without local recurrence.

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

    Directory of Open Access Journals (Sweden)

    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.

  8. Mitosis Detection for Invasive Breast Cancer Grading in Histopathological Images.

    Science.gov (United States)

    Paul, Angshuman; Mukherjee, Dipti Prasad

    2015-11-01

    Histopathological grading of cancer not only offers an insight to the patients' prognosis but also helps in making individual treatment plans. Mitosis counts in histopathological slides play a crucial role for invasive breast cancer grading using the Nottingham grading system. Pathologists perform this grading by manual examinations of a few thousand images for each patient. Hence, finding the mitotic figures from these images is a tedious job and also prone to observer variability due to variations in the appearances of the mitotic cells. We propose a fast and accurate approach for automatic mitosis detection from histopathological images. We employ area morphological scale space for cell segmentation. The scale space is constructed in a novel manner by restricting the scales with the maximization of relative-entropy between the cells and the background. This results in precise cell segmentation. The segmented cells are classified in mitotic and non-mitotic category using the random forest classifier. Experiments show at least 12% improvement in F1 score on more than 450 histopathological images at 40× magnification.

  9. High mammographic breast density predicts locoregional recurrence after modified radical mastectomy for invasive breast cancer: a case-control study.

    Science.gov (United States)

    Huang, Yu-Sen; Chen, Jenny Ling-Yu; Huang, Chiun-Sheng; Kuo, Sung-Hsin; Jaw, Fu-Shan; Tseng, Yao-Hui; Ko, Wei-Chun; Chang, Yeun-Chung

    2016-12-01

    We aimed to evaluate the influence of mammographic breast density at diagnosis on the risk of cancer recurrence and survival outcomes in patients with invasive breast cancer after modified radical mastectomy. This case-control study included 121 case-control pairs of women diagnosed with invasive breast cancer between 2004 and 2009, and who had undergone modified radical mastectomy and had mammographic breast density measured before or at diagnosis. Women with known locoregional recurrence or distant metastasis were matched by pathological disease stage, age, and year of diagnosis to women without recurrence. Locoregional recurrence was defined as recurrence in the ipsilateral chest wall, or axillary, internal mammary, or supraclavicular nodes. The median follow-up duration was 84.0 months for case patients and 92.9 months for control patients. Patients with heterogeneously dense (50-75% density) and extremely dense (>75% density) breasts had an increased risk of locoregional recurrence (hazard ratios 3.1 and 5.7, 95% confidence intervals 1.1-9.8 and 1.2-34.9, p = 0.043 and 0.048, respectively) than did women with less dense breasts. Positive margins after surgery also increased the risk of locoregional recurrence (hazard ratio 3.3, 95% confidence interval 1.3-8.3, p = 0.010). Multivariate analysis that included dense breasts (>50% density), positive margin, no adjuvant radiotherapy, and no adjuvant chemotherapy revealed that dense breasts were significant factors for predicting locoregional recurrence risk (hazard ratio 3.6, 95% confidence interval 1.2-11.1, p = 0.025). Our results demonstrate that dense breast tissue (>50% density) increased the risk of locoregional recurrence after modified radical mastectomy in patients with invasive breast cancer. Additional prospective studies are necessary to validate these findings. The study is retrospectively registered with ClinicalTrials.gov, number NCT02771665 , on May 11, 2016.

  10. 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

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

    International Nuclear Information System (INIS)

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

    2009-01-01

    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 (BK Ca ) 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 BK Ca 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 BK Ca 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 BK Ca 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 BK Ca channel activity, leading to greater invasiveness and transendothelial migration, both of which could be attenuated by blocking KCNMA1. Determining the relative abundance of BK Ca channel expression in breast cancer metastatic to brain and the mechanism of its

  12. [Lobular invasive breast cancer prognostic factors: About 940 patients].

    Science.gov (United States)

    Jauffret, C; Houvenaeghel, G; Classe, J-M; Garbay, J-R; Giard, S; Charitansky, H; Cohen, M; Bélichard, C; Faure, C; Darai, É; Hudry, D; Azuar, P; Villet, R; Gimbergues, P; Tunon de Lara, C; Martino, M; Coutant, C; Dravet, F; Chauvet, M-P; Chéreau Ewald, E; Penault-Llorca, F; Goncalves, A; Lambaudie, É

    2015-11-01

    significance (HR: 2,43, IC: 0,99-5,93). There was no detectable effect of chemotherapy regarding disease free survival (odds ratio [OR] 0,8, IC: 0,35-1,80) and overall survival (OR: 0,72, IC: 0,28-1,82). Disease free survival was similar between no axillary invasion (pN0) and isolated tumor cells (pNi+), or micrometastatic lymph nodes (pNmic). There were no difference neither between one or more than one macromatastatic lymph node. But disease free survival was statistically worse for pN1 compared to other lymph node status (pN0, pNi+ or pNmic). Factors associated with lymph node involvement after logistic regression was: age from 51 to 65 years (OR: 2,1, IC 1,45-3,04), age inferior to 50 years (OR 3,2, IC: 2,05-5,03), Tumour size superior to 2cm (OR 4,4, IC: 3,2-6,14), SBR grading 2 (OR 1,9, IC: 1,30-2,90) and SBR grade 3 (OR 3,5, IC: 1,61-7,75). The analysis of this series of 940 T1 and T2 lobular invasive breast carcinomas offers several information: factors associated with axillary lymph node involvement are age under 65 years, tumor size greater than 20mm, and a SBR grade 2 or 3. The same factors were significantly associated with the OS and DFS. The macrometastatic lymph node involvement has a significant impact on DFS and OS, which is not true for isolated cells and micrometastases, which seem to have the same prognosis as pN0. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  13. Elevated expression of LSD1 (Lysine-specific demethylase 1 during tumour progression from pre-invasive to invasive ductal carcinoma of the breast

    Directory of Open Access Journals (Sweden)

    Serce Nuran

    2012-08-01

    Full Text Available Abstract Background Lysine-specific demethylase1 (LSD1 is a nuclear protein which belongs to the aminooxidase-enzymes playing an important role in controlling gene expression. It has also been found highly expressed in several human malignancies including breast carcinoma. Our aim was to detect LSD1 expression also in pre-invasive neoplasias of the breast. In the current study we therefore analysed LSD1 protein expression in ductal carcinoma in situ (DCIS in comparison to invasive ductal breast cancer (IDC. Methods Using immunohistochemistry we systematically analysed LSD1 expression in low grade DCIS (n = 27, intermediate grade DCIS (n = 30, high grade DCIS (n = 31 and in invasive ductal breast cancer (n = 32. SPSS version 18.0 was used for statistical analysis. Results LSD1 was differentially expressed in DCIS and invasive ductal breast cancer. Interestingly, LSD1 was significantly overexpressed in high grade DCIS versus low grade DCIS. Differences in LSD1 expression levels were also statistically significant between low/intermediate DCIS and invasive ductal breast carcinoma. Conclusions LSD1 is also expressed in pre-invasive neoplasias of the breast. Additionally, there is a gradual increase of LSD1 expression within tumour progression from pre-invasive DCIS to invasive ductal breast carcinoma. Therefore upregulation of LSD1 may be an early tumour promoting event.

  14. 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

  15. 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.

  16. 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.

  17. Nuclear localization of the transcriptional coactivator YAP is associated with invasive lobular breast cancer.

    Science.gov (United States)

    Vlug, Eva J; van de Ven, Robert A H; Vermeulen, Jeroen F; Bult, Peter; van Diest, Paul J; Derksen, Patrick W B

    2013-10-01

    Yes Associated Protein (YAP) has been implicated in the control of organ size by regulating cell proliferation and survival. YAP is a transcriptional coactivator that controls cellular responses through interaction with TEAD transcription factors in the nucleus, while its transcriptional functions are inhibited by phosphorylation-dependent translocation to the cytosol. YAP overexpression has been associated with different types of cancer, such as lung, skin, prostate, ovary and liver cancer. Recently, YAP was linked to E-cadherin-dependent regulation of contact inhibition in breast cancer cells. In this study we examined YAP protein expression and cellular localization in 237 cases of human invasive breast cancer by immunohistochemistry and related its expression to clinicopathological features and E-cadherin expression. We observed that invasive lobular carcinoma is characterized by higher expression levels of both nuclear and cytosolic YAP (p invasive breast cancer. We observed that high nuclear and cytosolic YAP expression are associated with the E-cadherin deficient breast cancer subtype ILC (p cancers and conditional mouse models of human lobular breast cancer. Since our data indicate that nuclear YAP localization is more common in breast cancers lacking functional adherens junctions, it suggests that YAP-mediated transcription may be involved in the development and progression of invasive lobular breast cancer.

  18. Gastric metastasis from invasive lobular breast cancer, mimicking primary gastric cancer: A case report.

    Science.gov (United States)

    Kim, Dae Hoon; Son, Seung-Myoung; Choi, Young Jin

    2018-03-01

    Gastric metastasis from invasive lobular breast cancer is relatively rare, commonly presented among multiple metastases, several years after primary diagnosis of breast cancer. Importantly, gastric cancer that is synchronously presented with lobular breast cancer can be misdiagnosed as primary gastric cancer; therefore, accurate differential diagnosis is required. A 39-year-old woman was visited to our hospital because of right breast mass and progressive dyspepsia. Invasive lobular carcinoma of breast was diagnosed on core needle biopsy. Gastroscopy revealed a diffuse scirrhous mass at the prepyloric antrum and diagnosed as poorly differentiated adenocarcinoma on biopsy. Synchronous double primary breast and gastric cancers were considered. Detailed pathological analysis focused on immunohistochemical studies of selected antibodies, including those of estrogen receptors, gross cystic disease fluid protein-15, and caudal-type homeobox transcription factor 2, were studied. As a result, gastric lesion was diagnosed as metastatic gastric cancer originating from breast. Right breast conserving surgery was performed, and duodenal stent was inserted under endoscopic guidance to relieve the patient's symptoms. Systemic chemotherapy with combined administration of paclitaxel and trastuzumab was initiated. Forty-one months after the diagnosis, the patient is still undergoing the same therapy. No recurrent lesion has been identified in the breast and evidence of a partial remission of gastric wall thickening has been observed on follow-up studies without new metastatic lesions. Clinical suspicion, repeat endoscopic biopsy, and detailed histological analysis, including immunohistochemistry, are necessary for diagnosis of metastatic gastric cancer from the breast.

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

    International Nuclear Information System (INIS)

    Wenz, Frederik; Sperk, Elena; Budach, Wilfried; Dunst, Juergen; Feyer, Petra; Fietkau, Rainer; Sauer, Rolf; Haase, Wulf; Harms, Wolfgang; Piroth, Marc D.; Sautter-Bihl, Marie-Luise; Sedlmayer, Felix; Fussl, Christoph; Souchon, Rainer

    2014-01-01

    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 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.) [de

  20. Proanthocyanidin in red rice inhibits MDA-MB-231 breast cancer cell invasion via the expression control of invasive proteins.

    Science.gov (United States)

    Pintha, Komsak; Yodkeeree, Supachai; Limtrakul, Pornngarm

    2015-01-01

    Proanthocyanidin is one of the main active compounds found in red jasmine rice. We previously reported that red rice extract could reduce cancer cell invasion. However, the direct effect of proanthocyanidin from red rice on the invasion of cancer cells and the exact molecular mechanism remained unclear. Here, we report for the first time that proanthocyanidin-rich fraction from red rice (PRFR) reduced the migration and invasion of MDA-MB-231 human breast cancer cells. The types of proanthocyanidin in PRFR were identified as procyanidins and prodelphinidins by acid hydrolysis. For cancer cell invasion, degradation of the extracellular matrix (ECM) is required. Treatment of the cells with PRFR reduced the expression of ECM degradation-associated proteins, including matrix metalloproteinase-9 (MMP-9), membrane type-1 matrix metalloproteinase, urokinase plasminogen activator, urokinase plasminogen activator receptor and plasminogen activator-1. Moreover, PRFR also reduced the activity of collagenase and MMP-9. Furthermore, PRFR significantly suppressed the expression of intercellular adhesion molecule-1 and interleukin-6. We also found that PRFR reduced the DNA-binding activity of nuclear factor kappa B (NF-κB), which is the expressed mediator of ECM degradation-associated proteins. These results suggest that proanthocyanidin from red rice mediates MDA-MB-231 breast cancer cell invasion by altering the expression of the invasion-associated proteins, possibly by targeting NF-κB activity.

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

    International Nuclear Information System (INIS)

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

    2015-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-02-01

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

  3. Population-based study of peritumoral lymphovascular invasion and outcome among patients with operable breast cancer

    DEFF Research Database (Denmark)

    Ejlertsen, Bent; Jensen, Maj-Britt; Rank, Fritz

    2009-01-01

    report forms, central review, and querying, were specified in advance. Kaplan-Meier analyses were used to estimate disease-free intervals and overall survival rates among patients with and without lymphovascular invasion, and multivariable analysis was used to adjust for differences in baseline...... alive. These differences persisted in a multivariable analysis, and for overall survival, a statistically significant interaction (P = .03) was observed between lymphovascular invasion and risk group. CONCLUSIONS: In this prospective population-based study, lymphovascular invasion was not an independent......BACKGROUND: Lymphovascular invasion has been associated with poor prognosis in women with breast cancer, but it is unclear whether the presence of lymphovascular invasion should be considered sufficient to reclassify breast cancer patients who are at a low risk of recurrence into a high...

  4. Metastatic nonpalpable invasive lobular breast carcinoma presenting as rectal stenosis: a case report.

    Science.gov (United States)

    Osaku, Tadatoshi; Ogata, Hideaki; Magoshi, Shunsuke; Kubota, Yorichika; Saito, Fumi; Kanazawa, Shinsaku; Kaneko, Hironori

    2015-04-24

    Invasive lobular carcinomas have an increased propensity for distant metastases, particularly to the peritoneum, ovaries, and uterus. In contrast, distant metastases of nonpalpable lobular carcinomas are extremely rare, and the causes of underlying symptoms of primary carcinomas remain unclear. We report a case of an asymptomatic invasive lobular carcinoma with a primary mammary lesion in a patient with rectal stenosis. A 69-year-old Japanese woman presented to our hospital for treatment of constipation. Although rectal stenosis was confirmed, thorough testing of her lower digestive tract did not identify its cause. Thus, an exploratory laparotomy and tissue biopsy was performed, and the presence of an invasive lobular carcinoma was confirmed. Subsequent breast examinations showed that the invasive lobular carcinoma that led to the rectal stenosis was a metastatic lesion from a primary lesion of the breast duct. As the present breast lobular carcinoma was asymptomatic and nonpalpable, we did not initially consider metastatic breast cancer as a cause of her symptoms, and the final diagnosis was delayed. Peritoneal metastasis from nonpalpable invasive lobular carcinomas is very rare. However, breast cancer metastasis should be considered when carcinomatous peritonitis is present in a patient with an unknown primary cancer.

  5. Metallothionein-3 Increases Triple-Negative Breast Cancer Cell Invasiveness via Induction of Metalloproteinase Expression.

    Directory of Open Access Journals (Sweden)

    Alicja M Kmiecik

    Full Text Available It has been recently found that metallothionein-3 (MT3 enhances the invasiveness and tumorigenesis of prostate cancer cells. This finding is in contrast to those of earlier studies, which indicated that overexpression of MT3 in breast cancer and prostate cancer cell lines inhibits their growth in vitro. Therefore, to clarify the role of MT3 in breast cancer progression, we analyzed the effect of MT3-overexpression on proliferation, invasiveness, migration, and tumorigenesis of breast cancer MDA-MB-231/BO2 cells. It was found that MDA-MB-231/BO2 cells overexpressing MT3 were characterized by increased invasiveness in vitro, compared to the control cells. Interestingly, this increased invasiveness correlated with a highly increased concentration of MMP3 in the culture supernatants (p<0.0001. Our data suggest that MT3 may regulate breast cancer cell invasiveness by modulating the expression of MMP3. These experimental results, obtained using triple-negative MDA-MB-231/BO2 cells, were further supported by clinical data. It was found that, in triple-negative breast cancer (TNBC, nuclear MT3 immunoreactivity in cancer cells tended to be associated with patients' shorter disease-specific survival, suggesting that nuclear MT3 expression may be a potential marker of poor prognosis of triple-negative TNBC cases.

  6. Metallothionein-3 Increases Triple-Negative Breast Cancer Cell Invasiveness via Induction of Metalloproteinase Expression.

    Science.gov (United States)

    Kmiecik, Alicja M; Pula, Bartosz; Suchanski, Jaroslaw; Olbromski, Mateusz; Gomulkiewicz, Agnieszka; Owczarek, Tomasz; Kruczak, Anna; Ambicka, Aleksandra; Rys, Janusz; Ugorski, Maciej; Podhorska-Okolow, Marzena; Dziegiel, Piotr

    2015-01-01

    It has been recently found that metallothionein-3 (MT3) enhances the invasiveness and tumorigenesis of prostate cancer cells. This finding is in contrast to those of earlier studies, which indicated that overexpression of MT3 in breast cancer and prostate cancer cell lines inhibits their growth in vitro. Therefore, to clarify the role of MT3 in breast cancer progression, we analyzed the effect of MT3-overexpression on proliferation, invasiveness, migration, and tumorigenesis of breast cancer MDA-MB-231/BO2 cells. It was found that MDA-MB-231/BO2 cells overexpressing MT3 were characterized by increased invasiveness in vitro, compared to the control cells. Interestingly, this increased invasiveness correlated with a highly increased concentration of MMP3 in the culture supernatants (p<0.0001). Our data suggest that MT3 may regulate breast cancer cell invasiveness by modulating the expression of MMP3. These experimental results, obtained using triple-negative MDA-MB-231/BO2 cells, were further supported by clinical data. It was found that, in triple-negative breast cancer (TNBC), nuclear MT3 immunoreactivity in cancer cells tended to be associated with patients' shorter disease-specific survival, suggesting that nuclear MT3 expression may be a potential marker of poor prognosis of triple-negative TNBC cases.

  7. Patients with Invasive Lobular Breast Cancer Are Less Likely to Undergo Breast-Conserving Surgery: A Population Based Study in The Netherlands

    NARCIS (Netherlands)

    Truin, W.; Roumen, R.M.; Siesling, Sabine; van der Heiden-van der Loo, M.; Duijm, E.M.; Tjan-Heijnen, V.C.G.; Voogd, A.C.

    2015-01-01

    Purpose The aim of this study was to compare the frequency of breast-conserving surgery (BCS) between early-stage invasive ductal (IDC) and invasive lobular breast cancer (ILC). Methods Women with primary non-metastatic pT1 and pT2 IDC or ILC diagnosed between 1990 and 2010 were selected from the

  8. HN1 contributes to migration, invasion, and tumorigenesis of breast cancer by enhancing MYC activity.

    Science.gov (United States)

    Zhang, Chen; Xu, Bingfei; Lu, Shi; Zhao, Ying; Liu, Pian

    2017-05-11

    Hematological and neurological expressed 1 (HN1) is upregulated in many tumors, but the role of HN1 in breast cancer progression and its regulatory mechanism have not been well understood. To study the role of HN1 in the initiation and progression of breast cancer, we examined HN1 levels in breast cancer cells and tissues and analyzed the relationship between HN1 levels and patient survival. We used mammosphere formation assay, side population analysis, wound healing assay, transwell assay, soft agar formation assay, and xenografted tumor model to determine the effect of HN1 on the expansion of breast cancer stem cells, and the migration, invasion and tumorigenesis of breast cancer. To determine whether HN1 regulates MYC, we used quantitative real-time PCR and Western blot analysis to assess the expression of MYC and their targeted genes to determine the phenotype caused by knockdown of MYC in breast cancer cell with HN1 overexpression. In this study, we found that HN1 was upregulated in breast cancer tissues. Patients with high levels of HN1 expression had significantly shorter survival than those with low HN1 expression. In breast cancer cell line, ectopic overexpression of HN1 not only promoted the expansion of breast cancer stem cells, but also promoted cell migration, invasion, and tumorigenesis, while knockdown of HN1 reduced these effects. Furthermore, there was a positive correlation between MYC (also known as c-MYC) level and HN1 level, mechanism analysis suggested HN1 promoted the expression of MYC and its targeted genes like CDK4, CCND1, p21, CAV1, and SFRP1. Downregulation of MYC abrogated the effect of HN1 overexpression in breast cancer cell lines. Taken together, these data reveal that HN1 promotes the progression of breast cancer by upregulating MYC expression, and might be a therapeutic target for breast cancer.

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

    Science.gov (United States)

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

    2014-11-01

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

  10. 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

  11. 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.

  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......(-4)). Of the 75 known breast cancer polymorphisms that were genotyped, 56 were associated with ILC and 15 with LCIS at P... 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 rs...

  13. Correlation of MRI apparent diffusion coefficient of invasive breast cancer with tumor tissue growth and angiogenesis

    Directory of Open Access Journals (Sweden)

    Ze-Hong Fu

    2017-08-01

    Full Text Available Objective: To study the correlation of MRI apparent diffusion coefficient (ADC value of invasive breast cancer with tumor tissue growth and angiogenesis. Methods: Patients with breast mass who were treated in Wuhan No. 6 Hospital between March 2014 and May 2017 were selected as the research subjects and divided into group A with invasive ductal carcinoma, group B with intraductal carcinoma and group C with benign lesion according to the biopsy results, magnetic resonance diffusion-weighted imaging was conducted to determine ADC values, and biopsy tissue was taken to determine the expression of proliferation genes and angiogenesis genes. Results: USP39, CyclinD1, VEGF, bFGF, Angplt-2, Angplt-3 and Angplt-4 protein expression levels in lesions of group A and group B were significantly higher than those of group C while ADC value as well as ALEX1 and Bax protein expression levels were significantly lower than those of group C; USP39, CyclinD1, VEGF, bFGF, Angplt-2, Angplt-3 and Angplt-4 protein expression levels in lesions of group A were significantly higher than those of group B while ADC value as well as ALEX1 and Bax protein expression levels was significantly lower than those of group B; USP39, CyclinD1, VEGF, bFGF, Angplt-2, Angplt-3 and Angplt-4 protein expression levels in invasive breast cancer tissue with high ADC value were significantly lower than those in invasive breast cancer tissue with low ADC value while ALEX1 and Bax protein expression levels were significantly higher than those in invasive breast cancer tissue with low ADC value. Conclusion: The decrease of ADC value of invasive breast cancer is closely related to cancer cell proliferation and angiogenesis.

  14. Magnetic resonance imaging of invasive breast cancer | Corr | SA ...

    African Journals Online (AJOL)

    Breast MR is a sensitive but nonspecific imaging investigation to detect breast cancer. MR imaging strengths lie in the accurate staging of the primary tumour, detecting recurrent cancer following lumpectomy and radiation therapy, problem solving in cases where there are equivocal mammographic findings, and screening ...

  15. Use of Exogenous Progestins and Risk or In Situ and Invasive Breast Cancer

    Science.gov (United States)

    2011-10-01

    IRREGULAR OR HEAVY BLEEDING ........................................... [3] CANCER (OVARY, ENDOMETRIUM/UTERUS, CERVIX ) ........... [4] ENDOMETRIOSIS...maximum height is reached as a risk factor for breast cancer among young U.S. women. Epidemiology 1997;8:559-565. 3. van Oers HJJ, de Kloet ER, Li C...05-1-0482 TITLE: Use of Exogenous Progestins and Risk or In Situ and Invasive Breast Cancer PRINCIPAL INVESTIGATOR: Dr

  16. 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.

  17. Recruitment & Regulation of N-Wasp by F-Bar Family Member CIP4 in Invasive Breast Cancer Cells

    Science.gov (United States)

    2009-07-01

    The focus of this project is the contribution of the Cdc42-interacting protein CIP4 to the invasive phenotype of MDA-MB-231 cancer cells . CIP4 is a...breast cancer cell lines. My research investigates the role of CIP4 in promoting invasion and invadopodia in breast cancer cells in vitro through its

  18. Identification of EDIL3 on extracellular vesicles involved in breast cancer cell invasion.

    Science.gov (United States)

    Lee, Jeong-Eun; Moon, Pyong-Gon; Cho, Young-Eun; Kim, Young-Bum; Kim, In-San; Park, Hoyong; Baek, Moon-Chang

    2016-01-10

    Cancer cell-derived extracellular vesicles have been linked to the pathogenesis of various cancers; however, the role of extracellular vesicles in tumorigenesis remains unclear. To identify extracellular vesicle proteins involved in cancer metastasis, quantitative proteomic analyses were performed on extracellular vesicles derived from two representative breast cancer cell lines: the less invasive MCF-7 and the invasive MDA-MB-231. Proteomic analysis allowed for the identification of 270 proteins in the extracellular vesicles. Here we report a new function of EDIL3 on extracellular vesicles, which are sufficient for enhancement of cell invasion and for acceleration of lung metastasis in vivo. This invasion is most likely mediated via the integrin-FAK signaling cascade in breast cancer cells. However, these effects are suppressed when EDIL3 is inactivated, providing evidence for a critical role of EDIL3 in development of cancer. Consistently, in human patients with metastatic breast cancer, the levels of EDIL3 on circulating extracellular vesicles are significantly elevated. This information is a remarkable breakthrough in understanding of the molecular mechanism underlying metastasis of breast cancer as well as in the research for cancer biomarkers using circulating extracellular vesicles. Furthermore, targeting EDIL3 on extracellular vesicles may lead to a new therapeutic option for treatment of breast cancer. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. miRNA-135a promotes breast cancer cell migration and invasion by targeting HOXA10

    International Nuclear Information System (INIS)

    Chen, Yating; Zhang, Hongwei; Ma, Duan; Zhang, Jin; Wang, Huijun; Zhao, Jiayi; Xu, Cheng; Du, Yingying; Luo, Xin; Zheng, Fengyun; Liu, Rui

    2012-01-01

    miRNAs are a group of small RNA molecules regulating target genes by inducing mRNA degradation or translational repression. Aberrant expression of miRNAs correlates with various cancers. Although miR-135a has been implicated in several other cancers, its role in breast cancer is unknown. HOXA10 however, is associated with multiple cancer types and was recently shown to induce p53 expression in breast cancer cells and reduce their invasive ability. Because HOXA10 is a confirmed miR-135a target in more than one tissue, we examined miR-135a levels in relation to breast cancer phenotypes to determine if miR-135a plays role in this cancer type. Expression levels of miR-135a in tissues and cells were determined by poly (A)-RT PCR. The effect of miR-135a on proliferation was evaluated by CCK8 assay, cell migration and invasion were evaluated by transwell migration and invasion assays, and target protein expression was determined by western blotting. GFP and luciferase reporter plasmids were constructed to confirm the action of miR-135a on downstream target genes including HOXA10. Results are reported as means ± S.D. and differences were tested for significance using 2-sided Student's t-test. Here we report that miR-135a was highly expressed in metastatic breast tumors. We found that the expression of miR-135a was required for the migration and invasion of breast cancer cells, but not their proliferation. HOXA10, which encodes a transcription factor required for embryonic development and is a metastasis suppressor in breast cancer, was shown to be a direct target of miR-135a in breast cancer cells. Our analysis showed that miR-135a suppressed the expression of HOXA10 both at the mRNA and protein level, and its ability to promote cellular migration and invasion was partially reversed by overexpression of HOXA10. In summary, our results indicate that miR-135a is an onco-miRNA that can promote breast cancer cell migration and invasion. HOXA10 is a target gene for mi

  20. Reoperation Rates in Ductal Carcinoma In Situ vs Invasive Breast Cancer After Wire-Guided Breast-Conserving Surgery

    DEFF Research Database (Denmark)

    Langhans, Linnea; Jensen, Maj-Britt; Talman, Maj-Lis M

    2017-01-01

    to be established for comparison, as previous studies on this procedure include a variety of malignant and benign breast lesions. Objectives: To determine the reoperation rate after wire-guided BCS in patients with histologically verified nonpalpable invasive breast cancer (IBC) or ductal carcinoma in situ (DCIS......Importance: New techniques for preoperative localization of nonpalpable breast lesions may decrease the reoperation rate in breast-conserving surgery (BCS) compared with rates after surgery with the standard wire-guided localization. However, a valid reoperation rate for this procedure needs.......9 [8.7] years). A total of 725 patients (17.6%) underwent a reoperation: 593 were reexcisions (14.4%) and 132 were mastectomies (3.2%). Significantly more patients with DCIS (271 of 727 [37.3%]) than with IBC (454 of 3391 [13.4%]) underwent a reoperation (adjusted odds ratio, 3.82; 95% CI, 3.19-4.58; P...

  1. 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.

  2. 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.

  3. miR-613 inhibits proliferation and invasion of breast cancer cell via VEGFA

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Junzhao; Yuan, Peng; Mao, Qixin [Breast Surgery, The Affiliated Cancer Hospital of Zhengzhou University, Henan (China); Lu, Peng [Gastrointestinal Surgery Department, People' s Hospital of Zhengzhou, Henan (China); Xie, Tian; Yang, Hanzhao [Breast Surgery, The Affiliated Cancer Hospital of Zhengzhou University, Henan (China); Wang, Chengzheng, E-mail: wangchengzheng@126.com [Breast Surgery, The Affiliated Cancer Hospital of Zhengzhou University, Henan (China)

    2016-09-09

    MicroRNAs (miRNAs) play important roles in the pathogenesis of many types of cancers by negatively regulating gene expression at posttranscriptional level. However, the role of microRNAs in breast cancer, has remained elusive. Here, we identified that miR-613 inhibits breast cancer cell proliferation by negatively regulates its target gene VEGFA. In breast cancer cell lines, CCK-8 proliferation assay indicated that the cell proliferation was inhibited by miR-613, while miR-613 inhibitor significantly promoted the cell proliferation. Transwell assay showed that miR-613 mimics significantly inhibited the migration and invasion of breast cancer cells, whereas miR-613 inhibitors significantly increased cell migration and invasion. Luciferase assays confirmed that miR-613 directly bound to the 3′ untranslated region of VEGFA, and western blotting showed that miR-613 suppressed the expression of VEGFA at the protein levels. This study indicated that miR-613 negatively regulates VEGFA and inhibits proliferation and invasion of breast cancer cell lines. Thus, miR-613 may represent a potential therapeutic molecule for breast cancer intervention.

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

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Hongsheng [Department of Histology and Embryology, Guangdong Medical College, Dongguan 523808, Guangdong (China); Wu, Fenping [The 7th People’s Hospital of Chengdu, Chengdu 610041, Sichuan (China); Wang, Yan [The Second School of Clinical Medicine, Guangdong Medical College, Dongguan 523808, Guangdong (China); Yan, Chong [School of Pharmacy, Guangdong Medical College, Dongguan 523808, Guangdong (China); Su, Wenmei, E-mail: wenmeisutg@126.com [Oncology of Affiliated Hospital Guangdong Medical College, Zhanjiang 524000, Guangdong (China)

    2014-08-08

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

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

    International Nuclear Information System (INIS)

    Guo, Hongsheng; Wu, Fenping; Wang, Yan; Yan, Chong; Su, Wenmei

    2014-01-01

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

  6. 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.

  7. Comparative genomic hybridization analysis of benign and invasive male breast neoplasms

    DEFF Research Database (Denmark)

    Ojopi, Elida Paula Benquique; Cavalli, Luciane Regina; Cavalieri, Luciane Mara Bogline

    2002-01-01

    Comparative genomic hybridization (CGH) analysis was performed for the identification of chromosomal imbalances in two benign gynecomastias and one malignant breast carcinoma derived from patients with male breast disease and compared with cytogenetic analysis in two of the three cases. CGH...... and CGH analysis. CGH analysis of the invasive ductal carcinoma confirmed a gain of 17p11.2 through qter previously detected by cytogenetic analysis. These regions showed some similarity in their pattern of imbalance to the chromosomal alterations described in female and male breast cancer....

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

    Directory of Open Access Journals (Sweden)

    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.

  9. Impact of a prior diagnosis of DCIS on survival from invasive breast cancer.

    Science.gov (United States)

    Sopik, Victoria; Iqbal, Javaid; Sun, Ping; Narod, Steven A

    2016-07-01

    A diagnosis of invasive breast cancer after DCIS can be described as a new primary cancer or as a local invasive recurrence. It is of interest to determine if, among women with early-stage breast cancer, a past history of DCIS influences survival. We retrieved the records of 306,249 women diagnosed with stage I or stage II breast cancer between 2004 and 2012, in the surveillance, epidemiology, and end results registries database, of whom 5395 had a previous diagnosis of DCIS. For each patient, we extracted information on the year of diagnosis, age at diagnosis, tumor size, nodal status, grade, estrogen receptor status, type of surgery (lumpectomy/mastectomy), use of radiotherapy (no/yes), prior DCIS (no/yes), cause of death, and follow-up time. For each case with prior DCIS, we recorded information on the year of diagnosis of DCIS, laterality of DCIS, and treatments received for DCIS. We matched 3979 patients with a prior DCIS to 3979 patients without a prior DCIS, according to the various prognostic features of the invasive cancer. We estimated the risk of death from breast cancer for patients with invasive ductal carcinoma, with and without a prior diagnosis of DCIS. We identified 306,249 women with stage I/II breast cancer, of whom 2335 had a prior ipsilateral DCIS and 3060 had a prior contralateral DCIS. Breast cancer-specific survival at 9 years was 94.6 % for patients with a prior DCIS (ipsilateral or contralateral) and was 95.2 % for patients with no prior DCIS (p = 0.32). In a matched analysis (3979 matched pairs), the hazard ratio for death from breast cancer for patients with a prior ipsilateral DCIS, compared to patients with no prior DCIS, was 0.91 (95 % CI = 0.49-1.68; p = 0.75). A prior diagnosis of ipsilateral DCIS does not impact upon the prognosis of women with early-stage invasive breast cancer. This suggests that primary breast cancers and local invasive recurrences following DCIS are similar conditions and should be treated in the same

  10. GSE1 negative regulation by miR-489-5p promotes breast cancer cell proliferation and invasion

    Energy Technology Data Exchange (ETDEWEB)

    Chai, Peng, E-mail: chaiyisheng0508@sina.com [Department of General Surgery, The People' s Hospital of Bozhou, Bozhou 236800 (China); Tian, Jingzhong [Department of General Surgery, The People' s Hospital of Bozhou, Bozhou 236800 (China); Zhao, Deyin [Dept of General Surgery, The Hospital of Suzhou, Suzhou 234000 (China); Zhang, Hongyan; Cui, Jian [Department of General Surgery, The People' s Hospital of Bozhou, Bozhou 236800 (China); Ding, Keshuo [Department of Pathology, Anhui Medical University, Hefei 230022 (China); Liu, Bin, E-mail: 13399519008@163.com [Dept of Vascular Surgery, The First Affiliated Hospital, Anhui Medical University, Hefei 230022 (China)

    2016-02-26

    Gse1 coiled-coil protein (GSE1), also known as KIAA0182, is a proline rich protein. However, the function of GSE1 is largely unknown. In this study, we reported that GSE1 is overexpression in breast cancer and silencing of GSE1 significantly suppressed breast cancer cells proliferation, migration and invasion. Furthermore, GSE1 was identified as a direct target of miR-489-5p, which is significantly reduced in breast cancer tissues. In addition, forced expression of miR-489-5p suppressed breast cancer cells proliferation, migration and invasion. Moreover, depletion of GSE1 by siRNAs significantly abrogated the enhanced proliferation, migration and invasion of breast cancer cells consequent to miR-489-5p depletion. Taken together, these findings suggest that GSE1 may function as a novel oncogene in breast cancer and it can be regulated by miR-489-5p. - Highlights: • GSE1 is overexpressed in breast cancer and increased GSE1 expression predicts poor prognosis in breast cancer patients. • Knockdown of GSE1 inhibits breast cancer cell proliferation, migration and invasion. • GSE1 is a direct target of miR-489-5p. • Forced expression of miR-489-5p inhibits breast cancer cell proliferation, migration and invasion.

  11. Utilization of neoadjuvant chemotherapy varies in the treatment of women with invasive breast cancer.

    Directory of Open Access Journals (Sweden)

    Adedayo A Onitilo

    Full Text Available BACKGROUND: Treatment with neoadjuvant chemotherapy (NAC has made it possible for some women to be successfully treated with breast conservation therapy (BCT who were initially considered ineligible. Factors related to current practice patterns of NAC use are important to understand particularly as the surgical treatment of invasive breast cancer has changed. The goal of this study was to determine variations in neoadjuvant chemotherapy use in a large multi-center national database of patients with breast cancer. METHODS: We evaluated NAC use in patients with initially operable invasive breast cancer and potential impact on breast conservation rates. Records of 2871 women ages 18-years and older diagnosed with 2907 invasive breast cancers from January 2003 to December 2008 at four institutions across the United States were examined using the Breast Cancer Surgical Outcomes (BRCASO database. Main outcome measures included NAC use and association with pre-operatively identified clinical factors, surgical approach (partial mastectomy [PM] or total mastectomy [TM], and BCT failure (initial PM followed by subsequent TM. RESULTS: Overall, NAC utilization was 3.8%l. Factors associated with NAC use included younger age, pre-operatively known positive nodal status, and increasing clinical tumor size. NAC use and BCT failure rates increased with clinical tumor size, and there was significant variation in NAC use across institutions. Initial TM frequency approached initial PM frequency for tumors >30-40 mm; BCT failure rate was 22.7% for tumors >40 mm. Only 2.7% of patients undergoing initial PM and 7.2% undergoing initial TM received NAC. CONCLUSIONS: NAC use in this study was infrequent and varied among institutions. Infrequent NAC use in patients suggests that NAC may be underutilized in eligible patients desiring breast conservation.

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

    NARCIS (Netherlands)

    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

  13. Hypoxia-Targeting Fluorescent Nanobodies for Optical Molecular Imaging of Pre-Invasive Breast Cancer

    NARCIS (Netherlands)

    van Brussel, Aram S A; Adams, Arthur; Oliveira, Sabrina; Dorresteijn, Bram; El Khattabi, Mohamed; Vermeulen, J. F.; van der Wall, Elsken; Mali, Willem P Th M; Derksen, Patrick W B; van Diest, Paul J; van Bergen En Henegouwen, Paul M P

    PURPOSE: The aim of this work was to develop a CAIX-specific nanobody conjugated to IRDye800CW for molecular imaging of pre-invasive breast cancer. PROCEDURES: CAIX-specific nanobodies were selected using a modified phage display technology, conjugated site-specifically to IRDye800CW and evaluated

  14. Hypoxia-Targeting Fluorescent Nanobodies for Optical Molecular Imaging of Pre-Invasive Breast Cancer

    NARCIS (Netherlands)

    van Brussel, Aram S A; Adams, Arthur; Oliveira, Sabrina; Dorresteijn, Bram; El Khattabi, Mohamed; Vermeulen, Jeroen F.; van der Wall, Elsken; Mali, W.P.T.M.; Derksen, Patrick W B; van Diest, Paul J.; van Bergen En Henegouwen, Paul M P

    Purpose: The aim of this work was to develop a CAIX-specific nanobody conjugated to IRDye800CW for molecular imaging of pre-invasive breast cancer. Procedures: CAIX-specific nanobodies were selected using a modified phage display technology, conjugated site-specifically to IRDye800CW and evaluated

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

    Directory of Open Access Journals (Sweden)

    Bathmapriya Balakrishnan MD

    2016-03-01

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

  17. Concomitant endometrial and gallbladder metastasis in advanced multiple metastatic invasive lobular carcinoma of the breast: A rare case report.

    Science.gov (United States)

    Bezpalko, Kseniya; Mohamed, Mohamed A; Mercer, Leo; McCann, Michael; Elghawy, Karim; Wilson, Kenneth

    2015-01-01

    At time of presentation, fewer than 10% of patients have metastatic breast cancer. The most common sites of metastasis in order of frequency are bone, lung, pleura, soft tissue, and liver. Breast cancer metastasis to the uterus or gallbladder is rare and has infrequently been reported in the English literature. A 47 year old female with a recent history of thrombocytopenia presented with abnormal vaginal bleeding. Pelvic ultrasound revealed multiple uterine fibroids and endometrial curettings revealed cells consistent with lobular carcinoma of the breast. Breast examination revealed edema and induration of the lower half of the right breast. Biopsy of the right breast revealed invasive lobular carcinoma. Bone marrow aspiration obtained at a previous outpatient visit revealed extensive involvement by metastatic breast carcinoma. Shortly after discharge, the patient presented with acute cholecystitis and underwent cholecystectomy. Microscopic examination of the gallbladder revealed metastatic infiltrating lobular carcinoma. The final diagnosis was invasive lobular carcinoma of the right breast with metastasis to the bone marrow, endometrium, gallbladder, regional lymph nodes, and peritoneum. The growth pattern of invasive lobular carcinoma of the breast is unique and poses a challenge in diagnosing the cancer at an early stage. Unlike other types of breast cancer, it tends to metastasize more to the peritoneum, ovary, and gastrointestinal tract. Metastasis to the endometrium or gallbladder is rare. Metastatic spread should be considered in the differential diagnosis of patients with invasive lobular breast carcinoma presenting with abnormal vaginal bleeding or acute cholecystitis. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  18. Biologic markers in axillary node-negative breast cancer: differential expression in invasive ductal carcinoma versus invasive lobular carcinoma.

    Science.gov (United States)

    Gonzalez-Angulo, Ana Maria; Sahin, Aysegul; Krishnamurthy, Savitry; Yang, Ying; Kau, Shu-Wan; Hortobagyi, Gabriel N; Cristofanilli, Massimo

    2006-12-01

    The objective of this study was to compare the differential expression of established histopathologic and biologic markers of proliferation, apoptosis, and angiogenesis in invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) in a group of axillary node-negative breast cancers. Two hundred twenty patients with axillary node-negative ILC and IDC who underwent surgery at the University of Texas M. D. Anderson Cancer Center between 1978 and 1995 had tissue available for analysis. Of these, 206 (94%) had IDC and 14 (6%) had ILC. Estrogen receptors, progesterone receptors, tumor and stromal expression of vascular endothelial growth factor receptor 2, CD44, laminin-5, E-cadherin, and topoisomerase-2 were evaluated by immunohistochemical analysis. HER2/neu and alpha6beta4 integrin were evaluated by in situ hybridization. The Fisher exact test was used to calculate significant differences between ILC and IDC. Median age was 59 years. Invasive lobular carcinoma was more likely to occur in patients aged > 50 years. Invasive lobular carcinoma tended to be > 2 cm (50% vs. 39%), have a nuclear grade of 1/2 (100% vs. 72%), be estrogen receptor positive (93% vs. 70%), HER2/neu negative (92% vs. 68%), have high CD44 expression (31% vs. 16%), low stromal vascular endothelial growth factor receptor 2 expression (36% vs. 47%), no E-cadherin expression (0 vs. 90%), and low laminin-5 expression (15% vs. 25%), compared with IDC. Invasive lobular carcinoma and IDC might be distinct histologic types of breast cancer with different expression of biologic markers. These differences, not all being statistically significant in this small study, might generate hypotheses to develop tailored options for future systemic therapy.

  19. Investigating mechanisms of alkalinization for reducing primary breast tumor invasion.

    Science.gov (United States)

    Robey, Ian F; Nesbit, Lance A

    2013-01-01

    The extracellular pH (pHe) of many solid tumors is acidic as a result of glycolytic metabolism and poor perfusion. Acidity promotes invasion and enhances metastatic potential. Tumor acidity can be buffered by systemic administration of an alkaline agent such as sodium bicarbonate. Tumor-bearing mice maintained on sodium bicarbonate drinking water exhibit fewer metastases and survive longer than untreated controls. We predict this effect is due to inhibition of tumor invasion. Reducing tumor invasion should result in fewer circulating tumor cells (CTCs). We report that bicarbonate-treated MDA-MB-231 tumor-bearing mice exhibited significantly lower numbers of CTCs than untreated mice (P cancer where systemic alkalinization slows the rate of invasion.

  20. Mammotome HH biopsy - the future of minimal invasive breast surgery?

    International Nuclear Information System (INIS)

    Pietrzyk, G.; Nowicki, J.; Bojarski, B.; Kedzierski, B.; Wysocki, A.; Prudlak, E.

    2007-01-01

    Vacuum-assisted breast biopsy / Mammotome HH '' R '' Breast Biopsy System/ is the milestone in the diagnosis of breast lesions. This system has proven to be as diagnostically reliable as open surgery, but without scarring, deformations and hospitalizations associated with an open procedure. The aim of our study was to assess the role and possibilities of using this biopsy in treatment of benign breast lesions like fibroadenoma. From 2001 to 2004, about 1118 Mammotome biopsies were performed in our Department. Among 445 Mammotome biopsies performed under US control there were 211 cases of fibroadenomas. Follow-up was performed in 156 patients with this result at 6 and 12 months after biopsy. In our study we took into considerations the size, localizations as well as performers. In 2002 there were 70.8% patients with total lesion excision, 16.7% with residual lesion and 12.5% women with hematomas or scars. In 2003-2004 there were more women with total lesion excision (84.3%), fewer residual tumors and other lesions. In future, Mammotome breast biopsy can replace scalpel, and will become an alternative method to open surgical excision of fibroadenomas. It is important especially in the cases of young women to prevent cosmetic deformations and scars. (author)

  1. 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....... Using unbiased stereology, the three-dimensional mean nuclear size, v v(nuc), was estimated in routine histological sections, along with morphometric point-counting based estimates of the mean nuclear profile area, aH(nuc), and estimates of the nuclear density index, NI, the mitotic index, MI......) with those obtained in tumors of pure lobular carcinoma in situ (N = 7), only the difference in mean NI reached statistical significance (2p = 0.001). Several significant differences were found between means of quantitative histopathological estimates obtained in normal breast epithelium, pure in situ...

  2. 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....... Using unbiased stereology, the three-dimensional mean nuclear size, v v(nuc), was estimated in routine histological sections, along with morphometric point-counting based estimates of the mean nuclear profile area, aH(nuc), and estimates of the nuclear density index, NI, the mitotic index, MI...... obtained in tumors of pure lobular carcinoma in situ (N = 7), only the difference in mean NI reached statistical significance (2p = 0.001). Several significant differences were found between means of quantitative histopathological estimates obtained in normal breast epithelium, pure in situ lesions...

  3. Update on raloxifene: role in reducing the risk of invasive breast cancer in postmenopausal women

    Directory of Open Access Journals (Sweden)

    Vogel VG

    2011-10-01

    Full Text Available Victor G Vogel Cancer Institute, Geisinger Health System, Danville, PA, USA Abstract: Risk factors allow us to define women who are at increased lifetime risk for breast cancer, and the most important factor is age. Benign breast disease increases risk, and the most important histologies are atypical lobular or ductal hyperplasia and lobular carcinoma in situ. Family history of breast cancer among first-degree relatives (mother, sisters, daughters also increases risk. Quantitative measures of risk give accurate predictions of breast cancer incidence for groups of women but not for individual subjects. Multiple published, randomized controlled trials, which employed selective estrogen receptor (ER modulators (SERMs, have demonstrated consistent reductions of 35% or greater in the risk of ER-positive invasive and noninvasive breast cancer in postmenopausal women. Professional organizations in the US now recommend the use of SERMs to reduce the risk of breast cancer in high-risk, postmenopausal women. Raloxifene and tamoxifen reduce the risk of ER-positive invasive breast cancer with equal efficacy, but raloxifene is associated with a lower risk of thromboembolic disease, benign uterine conditions, and cataracts than tamoxifen in postmenopausal women. No evidence exists establishing whether a reduction in breast cancer risk from either agent translates into reduced breast cancer mortality. Overall quality of life is similar with raloxifene or tamoxifen, but the incidence of dyspareunia, weight gain, and musculoskeletal complaints is higher with raloxifene use, whereas vasomotor symptoms, bladder incontinence, gynecologic symptoms, and leg cramps were higher with tamoxifen use. Keywords: selective estrogen receptor modulators (SERMs, raloxifene, risk reduction, chemoprevention

  4. 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.

  5. 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.

  6. Clinical significance of CD151 overexpression in subtypes of invasive breast cancer.

    Science.gov (United States)

    Kwon, M J; Park, S; Choi, J Y; Oh, E; Kim, Y J; Park, Y-H; Cho, E Y; Kwon, M J; Nam, S J; Im, Y-H; Shin, Y K; Choi, Y-L

    2012-02-28

    CD151 is a member of the tetraspanin family, which interacts with laminin-binding integrins and other tetraspanins. This protein is implicated in motility, invasion, and metastasis of cancer cells, but the prevalence of CD151 expression in subtypes of breast cancers and its influence on clinical outcome remains to be evaluated. The immunohistochemistry-based tissue microarray analysis showed that 127 (14.3%) cases overexpressed CD151 among 886 breast cancer patients. CD151 overexpression was found to be significantly associated with larger tumour size, higher nodal stage, advanced stage, absence of oestrogen receptor and progesterone receptor, and human epidermal growth factor receptor 2 overexpression. CD151 overexpression resulted in poorer overall survival (OS) (Pbreast cancer (QNBC) subtypes, one subgroup of triple-negative breast cancer (P=0.0170). Multivariate analysis that included stage, subtype, and adjuvant chemotherapy showed that CD151 overexpression was independently associated with poor OS in invasive breast cancer. CD151 overexpression may be a potential molecular therapeutic target for breast cancer, especially in QNBC subtype and more advanced stages of breast cancer.

  7. Urinary Cadmium and Risk of Invasive Breast Cancer in the Women's Health Initiative

    Science.gov (United States)

    Adams, Scott V.; Shafer, Martin M.; Bonner, Matthew R.; LaCroix, Andrea Z.; Manson, JoAnn E.; Meliker, Jaymie R.; Neuhouser, Marian L.; Newcomb, Polly A.

    2016-01-01

    Cadmium is a widespread heavy metal pollutant that may act as an exogenous estrogenic hormone. Environmental cadmium exposure has been associated with risk of breast cancer in retrospective studies. We prospectively assessed the relationship between cadmium exposure, evaluated by creatinine-normalized urinary cadmium concentration, and invasive breast cancer among 12,701 postmenopausal women aged ≥50 years in a Women's Health Initiative study of bone mineral density. After a median of 13.2 years of follow-up (1993–2010), 508 cases of invasive breast cancer and 1,050 comparison women were identified for a case-cohort analysis. Multivariable Cox regression was used to calculate hazard ratios and 95% confidence intervals. Risk of breast cancer was not associated with urinary cadmium parameterized either in quartiles (comparing highest quartile with lowest, hazard ratio = 0.80, 95% confidence interval: 0.56, 1.14; P for trend = 0.20) or as a log-transformed continuous variable (per 2-fold higher urinary cadmium concentration, hazard ratio = 0.94, 95% confidence interval: 0.86, 1.03). We did not observe an association between urinary cadmium and breast cancer risk in any subgroup examined, including never smokers and women with body mass index (weight (kg)/height (m)2) less than 25. Results were consistent in both estrogen receptor–positive and estrogen receptor–negative tumors. Our results do not support the hypothesis that environmental cadmium exposure is associated with risk of postmenopausal breast cancer. PMID:27037269

  8. Ki-67 marker useful for classification of malignant invasive ductal breast cancer

    Directory of Open Access Journals (Sweden)

    Irmawati Hassan

    2013-12-01

    Full Text Available BACKGROUND Breast cancer is an important health problem in the world. Uncontrolled cell proliferation represents a malignant characteristic of neoplasia such as breast cancer, and can be examined immunohistochemically by measuring the Ki-67 proliferative marker. The objective of this study was to determine the role of Ki-67 for classification of the degree of malignancy in women with invasive ductal breast cancer. METHODS A cross-sectional study was conducted on 20 women with invasive ductal breast cancer. The samples were immuno-histochemically tested for Ki-67 using anti-Ki-67 primary antibody. The Ki-67 proliferative index was determined by enumerating the proportion of Ki-67 positive nuclei among the total number of cells in ten areas observed at 400x magnification, using a 20% cut-off value to distinguish between low and high proliferative indices. Statistical analysis was by means of the chi-square test. RESULTS Seventy five persent of the high grade malignancies had a high Ki-67 proliferative index (>20%, while only 12.5% of the low grade malignancies had a high Ki-67 index (>20%. The difference in grade malignancy was statistically significant (p=0.022, whereas tumor size was not associated with a statistically significant difference in Ki-67 index (p=0.648. CONCLUSION 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.

  9. Nuclear Kaiso expression is associated with high grade and triple-negative invasive breast cancer.

    Directory of Open Access Journals (Sweden)

    Jeroen F Vermeulen

    Full Text Available Kaiso is a BTB/POZ transcription factor that is ubiquitously expressed in multiple cell types and functions as a transcriptional repressor and activator. Little is known about Kaiso expression and localization in breast cancer. Here, we have related pathological features and molecular subtypes to Kaiso expression in 477 cases of human invasive breast cancer. Nuclear Kaiso was predominantly found in invasive ductal carcinoma (IDC (p = 0.007, while cytoplasmic Kaiso expression was linked to invasive lobular carcinoma (ILC (p = 0.006. Although cytoplasmic Kaiso did not correlate to clinicopathological features, we found a significant correlation between nuclear Kaiso, high histological grade (p = 0.023, ERα negativity (p = 0.001, and the HER2-driven and basal/triple-negative breast cancers (p = 0.018. Interestingly, nuclear Kaiso was also abundant in BRCA1-associated breast cancer (p<0.001 and invasive breast cancer overexpressing EGFR (p = 0.019. We observed a correlation between nuclear Kaiso and membrane-localized E-cadherin and p120-catenin (p120 (p<0.01. In contrast, cytoplasmic p120 strongly correlated with loss of E-cadherin and low nuclear Kaiso (p = 0.005. We could confirm these findings in human ILC cells and cell lines derived from conditional mouse models of ILC. Moreover, we present functional data that substantiate a mechanism whereby E-cadherin controls p120-mediated relief of Kaiso-dependent gene repression. In conclusion, our data indicate that nuclear Kaiso is common in clinically aggressive ductal breast cancer, while cytoplasmic Kaiso and a p120-mediated relief of Kaiso-dependent transcriptional repression characterize ILC.

  10. MCP-1 is overexpressed in triple-negative breast cancers and drives cancer invasiveness and metastasis.

    Science.gov (United States)

    Dutta, Pranabananda; Sarkissyan, Marianna; Paico, Kimberly; Wu, Yanyuan; Vadgama, Jaydutt V

    2018-03-28

    Triple-negative breast cancer (TNBC) is the most aggressive type of breast cancer that lacks ER/PR and HER2 receptors. Hence, there is urgency in developing new or novel therapeutic strategies for treatment of TNBC. Our study shows that the Monocyte Chemoattractant Protein-1 (MCP-1) is a marker associated with TNBC and may play a key role in TNBC disease progression. ELISA method was used to measure secreted MCP-1, and mRNA levels were determined by Real-time PCR in numerous cancer cell lines, representing various breast cancer subtypes. Cellular invasiveness was determined by Boyden chamber assay. Our data show that MCP-1 is upregulated in TNBC cell lines both transcriptionally as well as in secreted protein levels compared to ER-positive luminal cell line, MCF-7. Breast cancer patients, with Basal or Claudin-low subtypes, also showed high expression of MCP-1. MCP-1 treatment induced cell invasion in various breast cancer cell types, without affecting cell proliferation. Small molecule antagonists against Chemokine Receptor 2 (CCR2), cognate receptor for MCP-1 as well as the MAP kinase pathway inhibitor U0126 negatively affected MCP-1 induced MCF-7 cell invasion. This suggests that MCP-1-CCR2 axis may regulate invasiveness via the MAP Kinase pathway. Knocking down MCP-1 decreased cell invasion in TNBC cell line BT-549, along with downregulation of key epithelial to mesenchymal transition markers, N-cadherin and Vimentin. Our study suggests that MCP-1 mediated pathways could be potential therapeutic targets for the treatment of TNBC, and could reduce cancer health disparities.

  11. Low doses ionizing radiation enhances the invasiveness of breast cancer cells by inducing epithelial-mesenchymal transition

    International Nuclear Information System (INIS)

    Zhang, Xin; Li, Xiaoyan; Zhang, Ning; Yang, Qifeng; Moran, Meena S.

    2011-01-01

    Highlights: → Low doses ionizing irradiation would enhance the invasiveness of breast cancer cells by inducing EMT. → Low doses ionizing radiation induced morphologic changes in breast cancer cells. → Low doses ionizing radiation led to upregulation of mesenchymal markers and down-regulation of epithelial markers. → Low doses ionizing radiation increased migration and invasion of breast cancer cells. -- Abstract: Epithelial-mesenchymal transition (EMT) is a process cellular morphologic and molecular alterations facilitate cell invasion. We hypothesized that low dose ionizing irradiation (LDIR) enhances the invasiveness of breast cancer cells by inducing EMT. The effects of LDIR on cellular morphology and the EMT markers of MCF-7 breast cancer cells were analyzed by western blot/RT-PCR and migration/invasion was examined using the transwell assay. We found that LDIR led to the phenotypic changes of EMT in MCF-7 cells and down-regulation of epithelial differentiation markers and transcriptional induction of mesenchymal markers. Furthermore, the radiated cells demonstrated enhanced migration/invasion MCF-7 cells compared with non-radiated cells. In summary, LDIR promotes the invasiveness of breast cancer cells through epithelial to mesenchymal transition. These findings may ultimately provide a new targeted approach for improving the therapeutic effectiveness of radiation in breast cancer.

  12. 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

    To complement and update the 2007 practice guidelines of the breast cancer expert panel of the German Society of Radiation Oncology (DEGRO) for radiotherapy (RT) of breast cancer. Owing to its growing clinical relevance, in the current version, a separate paper is dedicated to non-invasive proliferating epithelial neoplasia of the breast. In addition to the more general statements of the German interdisciplinary S3 guidelines, this paper is especially focused on indication and technique of RT in addition to breast conserving surgery. The DEGRO expert panel performed a comprehensive survey of the literature comprising recently published data from clinical controlled trials, systematic reviews as well as meta-analyses, referring to the criteria of evidence-based medicine yielding new aspects compared to 2005 and 2007. The literature search encompassed the period 2008 to September 2012 using databases of PubMed and Guidelines International Network (G-I-N). Search terms were ''non invasive breast cancer'', ''ductal carcinoma in situ, ''dcis'', ''borderline breast lesions'', ''lobular neoplasia'', ''radiotherapy'' and ''radiation therapy''. In addition to the more general statements of the German interdisciplinary S3 guidelines, this paper is especially focused on indications of RT and decision making of non-invasive neoplasia of the breast after surgery, especially ductal carcinoma in situ. Among different non-invasive neoplasia of the breast only the subgroup of pure ductal carcinoma in situ (DCIS; synonym ductal intraepithelial neoplasia, DIN) is considered for further recurrence risk reduction treatment modalities after complete excision of DCIS, particularly RT following breast conserving surgery (BCS), in order to avoid a mastectomy. About half of recurrences are invasive cancers. Up to 50?% of all recurrences require salvage mastectomy

  13. Dihydroavenanthramide D inhibits human breast cancer cell invasion through suppression of MMP-9 expression

    International Nuclear Information System (INIS)

    Lee, Young-Rae; Noh, Eun-Mi; Oh, Hyun Ju; Hur, Hyun; Kim, Jeong-Mi; Han, Ji-Hey; Hwang, Jin-Ki; Park, Byung-Hyun; Park, Jin-Woo; Youn, Hyun Jo; Jung, Sung Hoo; Kim, Byeong-Soo; Jung, Ji-Youn; Lee, Sung-Ho; Park, Chang-Sik; Kim, Jong-Suk

    2011-01-01

    Research highlights: → MMP-9 plays a pivotal role in the invasion of MCF-7 breast cancer cells. → TPA stimulates MMP-9 expression through activation of MAPK/NF-κB and MAPK/AP-1 pathways. → Dihydroavenanthramide D suppresses MMP-9 expression via inhibition of TPA-induced MAPK/NF-κB and MAPK/AP-1 activations. → Dihydroavenanthramide D blocks cell invasion of MCF-7 breast cancer cells. -- Abstract: Dihydroavenanthramide D (DHAvD) is a synthetic analog to naturally occurring avenanthramide, which is the active component of oat. Previous study demonstrates that DHAvD strongly inhibits activation of nuclear factor-kappa B (NF-κB), which is a major component in cancer cell invasion. The present study investigated whether DHAvD can modulate MMP-9 expression and cell invasion in MCF-7 human breast cancer cells. MMP-9 expression and cell invasion in response to 12-O-tetradecanoylphorbol-13-acetate (TPA) was increased, whereas these inductions were muted by DHAvD. DHAvD also suppressed activation of mitogen-activated protein kinase (MAPK), and MAPK-mediated nuclear factor-kappa B (NF-κB) and activator protein-1 (AP-1) activations in TPA-treated MCF-7 cells. The results indicate that DHAvD-mediated inhibition of TPA-induced MMP-9 expression and cell invasion involves the suppression of the MAPK/NF-κB and MAPK/AP-1 pathways in MCF-7 cells. DHAvD may have potential value in breast cancer metastasis.

  14. Dietary Cadmium and Risk of Invasive Postmenopausal Breast Cancer in the VITAL Cohort

    Science.gov (United States)

    Adams, Scott V.; Newcomb, Polly A.; White, Emily

    2012-01-01

    Purpose Estimate the association between dietary intake of cadmium, a carcinogenic heavy metal, and risk of invasive breast cancer. Methods Study subjects were 30,543 postmenopausal women in the VITamins And Lifestyle (VITAL) cohort who completed a food frequency questionnaire (FFQ) at baseline (2000–2002). Dietary cadmium consumption was estimated by combining FFQ responses with US Food and Drug Administration data on food cadmium content. Incidence of invasive breast cancer was ascertained through linkage of the cohort to the western Washington Surveillance, Epidemiology, and End Results cancer registry through December 31, 2009. Cox regression was applied to estimate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for breast cancer with increasing dietary cadmium intake, adjusted for total energy intake, smoking history, consumption of vegetables, potatoes, and whole grains, multivitamin use, education, race, body mass index, physical activity, age at first birth, postmenopausal hormone use, and mammography. Results Vegetables and grains together contributed an average of 66% of estimated dietary cadmium. During a mean of 7.5 years of follow-up, 1,026 invasive postmenopausal breast cancers were identified. Among 899 cases with complete covariate information, no evidence of an association between dietary cadmium intake and breast cancer risk was observed (aHR (95% CI), highest to lowest quartile cadmium: 1.00 (0.72–1.41), Ptrend=0.95). No evidence was found for interactions between dietary cadmium and breast cancer risk factors, smoking habits, or total intake of calcium, iron, or zinc from diet, supplements, and multivitamins. Conclusions This study does not support the hypothesis that dietary cadmium intake is a risk factor for breast cancer. However, non-differential measurement error in the estimate of cadmium intake is likely the most important factor that could have obscured an association. PMID:22527162

  15. 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.

  16. 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.

  17. The Runx transcriptional co-activator, CBFβ, is essential for invasion of breast cancer cells

    Directory of Open Access Journals (Sweden)

    Lopez-Camacho Cesar

    2010-06-01

    Full Text Available Abstract Background The transcription factor Runx2 has an established role in cancers that metastasize to bone. In metastatic breast cancer cells Runx2 is overexpressed and contributes to the invasive capacity of the cells by regulating the expression of several invasion genes. CBFβ is a transcriptional co-activator that is recruited to promoters by Runx transcription factors and there is considerable evidence that CBFβ is essential for the function of Runx factors. However, overexpression of Runx1 can partially rescue the lethal phenotype in CBFβ-deficient mice, indicating that increased levels of Runx factors can, in some situations, overcome the requirement for CBFβ. Since Runx2 is overexpressed in metastatic breast cancer cells, and there are no reports of CBFβ expression in breast cells, we sought to determine whether Runx2 function in these cells was dependent on CBFβ. Such an interaction might represent a viable target for therapeutic intervention to inhibit bone metastasis. Results We show that CBFβ is expressed in the metastatic breast cancer cells, MDA-MB-231, and that it associates with Runx2. Matrigel invasion assays and RNA interference were used to demonstrate that CBFβ contributes to the invasive capacity of these cells. Subsequent analysis of Runx2 target genes in MDA-MB-231 cells revealed that CBFβ is essential for the expression of Osteopontin, Matrixmetalloproteinase-13, Matrixmetalloproteinase-9, and Osteocalcin but not for Galectin-3. Chromatin immunoprecipitation analysis showed that CBFβ is recruited to both the Osteopontin and the Galectin-3 promoters. Conclusions CBFβ is expressed in metastatic breast cancer cells and is essential for cell invasion. CBFβ is required for expression of several Runx2-target genes known to be involved in cell invasion. However, whilst CBFβ is essential for invasion, not all Runx2-target genes require CBFβ. We conclude that CBFβ is required for a subset of Runx2-target genes

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

    Science.gov (United States)

    Sherman, Mark E; Ichikawa, Laura; Pfeiffer, Ruth M; Miglioretti, Diana L; Kerlikowske, Karla; Tice, Jeffery; Vacek, Pamela M; Gierach, Gretchen L

    2016-01-01

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

  19. 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.

  20. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  2. Lactoferrin- Endothelin-1 Axis Contributes to the Development and Invasiveness of Triple Negative Breast Cancer Phenotypes

    Science.gov (United States)

    Ha, Ngoc-Han; Nair, Vasudha; Reddy, Divijendra Natha Sirigiri; Mudvari, Prakriti; Ohshiro, Kazufumi; Ghanta, Krishna Sumanth; Pakala, Suresh B.; Li, Da-Qiang; Costa, Luis; Lipton, Allan; Badwe, Rajendra A.; Fuqua, Suzanne; Wallon, Margaretha; Prendergast, George C.; Kumar, Rakesh

    2013-01-01

    Triple-negative breast cancer (TNBC) is characterized by the lack of expression of ERα, PR and HER-2 receptors and the pathway(s) responsible for this downregulation and thus aggressiveness, remains unknown. Here we discovered that lactoferrin (Lf) efficiently downregulates the levels of ERα, PR and HER-2 receptors in a proteasome-dependent manner in breast cancer cells, and accounts for the loss of responsiveness to ER- or HER-2- targeted therapies. Further we found that Lf increases migration and invasiveness of both non-TNBC and TNBC cell lines. We discovered that Lf directly stimulates the transcription of endothelin-1 (ET-1), a secreted pro-invasive polypeptide that acts through a specific receptor ET(A)R, leading to secretion of bioactive ET-1 peptide. Interestingly, a therapeutic ET-1 receptor antagonist drug completely blocked Lf-dependent motility and invasiveness of breast cancer cells. Physiologic significance of this newly discovered Lf-ET-1 axis in the manifestation of TNBC phenotypes is revealed by elevated plasma and tissue Lf and ET-1 levels in TNBC patients as compared to those in ER+ cases. These findings describe the first physiologically relevant polypeptide as a functional determinant of downregulating all three therapeutic receptors in breast cancer which utilizes another secreted ET-1 system to confer invasiveness. Results presented here provide proof-of-principle evidence in support of therapeutic effectiveness of ET-1 receptor antagonist to completely block the Lf-induced motility and invasiveness of the TNBC as well as non-TBNC cells, and thus, opening a remarkable opportunity to treat TNBC by targeting the Lf-ET-1 axis using an approved developmental drug. PMID:22006997

  3. Accuracy of contrast-enhanced breast ultrasound for pre-operative tumor size assessment in patients diagnosed with invasive ductal carcinoma of the breast

    Science.gov (United States)

    van Esser, S.; Veldhuis, W.B.; van Hillegersberg, R.; van Diest, P.J.; Stapper, G.; ElOuamari, M.; Borel Rinkes, I.H.M.; Mali, W.P.Th.M.

    2007-01-01

    Abstract Our aim was to assess the feasibility and accuracy of contrast-enhanced ultrasound (CEUS) of the breast with SonoVue microbubbles for pre-operative size measurement of invasive breast carcinomas. Seven patients diagnosed with nine invasive breast carcinomas prospectively underwent gray-scale ultrasound and CEUS of the breast according to a standardized protocol. CEUS of the breast was performed by a Philips iU22 scanner equipped with a 4–8 MHz linear array transducer. We used a single dose of 2.4 ml SonoVue as contrast agent. Breast lesion morphology was scored according to the sonographic BI-RADS lexicon criteria and classified accordingly. The greatest tumor dimensions on gray-scale ultrasound and CEUS of the breast were finally compared with the greatest histopathologic tumor sizes. Gray-scale ultrasound underestimated the histopathologic tumor size in 6/9 cases (67%), whereas CEUS of the breast underestimated tumor size in only 3/9 (33%) cases. CEUS of the breast was significantly more accurate for tumor size assessment. Greatest tumor dimension as measured with gray-scale ultrasound of the breast was within 2 mm of the pathologic tumor size in only 2/9 cases (22%), whereas CEUS of the breast accurately assessed tumor size within 2 mm of pathologic tumor size in 6/9 (67%) of the cases (P<0.05). CEUS of the breast proved to be a feasible and safe procedure. It is more accurate than gray-scale ultrasound of the breast for pre-operative size assessment of invasive ductal breast carcinomas. PMID:17513187

  4. Increased detection of lymphatic vessel invasion by D2-40 (podoplanin) in early breast cancer: possible influence on patient selection for accelerated partial breast irradiation.

    NARCIS (Netherlands)

    Debald, M.; Polcher, M.; Flucke, U.E.; Walgenbach-Brunagel, G.; Walgenbach, K.J.; Holler, T.; Wolfgarten, M.; Rudlowski, C.; Buttner, R.; Schild, H.; Kuhn, W.; Braun, M.

    2010-01-01

    PURPOSE: Several international trials are currently investigating accelerated partial breast irradiation (APBI) for patients with early-stage breast cancer. According to existing guidelines, patients with lymphatic vessel invasion (LVI) do not qualify for APBI. D2-40 (podoplanin) significantly

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

    Directory of Open Access Journals (Sweden)

    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.

  6. 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

  7. Estrogen Receptor and Progesterone Receptor Expression in Normal Terminal Duct Lobular Units Surrounding Invasive Breast Cancer

    Science.gov (United States)

    Yang, Xiaohong R.; Figueroa, Jonine D.; Hewitt, Stephen M.; Falk, Roni T.; Pfeiffer, Ruth M.; Lissowska, Jolanta; Peplonska, Beata; Brinton, Louise A.; Garcia-Closas, Montserrat; Sherman, Mark E.

    2014-01-01

    Introduction Molecular and morphological alterations related to carcinogenesis have been found in terminal duct lobular units (TDLUs), the microscopic structures from which most breast cancer precursors and cancers develop, and therefore, analysis of these structures may reveal early changes in breast carcinogenesis and etiologic heterogeneity. Accordingly, we evaluated relationships of breast cancer risk factors and tumor pathology to estrogen receptor (ER) and progesterone receptor (PR) expression in TDLUs surrounding breast cancers. Methods We analyzed 270 breast cancer cases included in a population-based breast cancer case-control study conducted in Poland. TDLUs were mapped in relation to breast cancer: within the same block as the tumor (TDLU-T), proximal to tumor (TDLU-PT), or distant from (TDLU-DT). ER/PR was quantitated using image analysis of immunohistochemically stained TDLUs prepared as tissue microarrays. Results In surgical specimens containing ER-positive breast cancers, ER and PR levels were significantly higher in breast cancer cells than in normal TDLUs, and higher in TDLU-T than in TDLU-DT or TDLU-PT, which showed similar results. Analyses combining DT-/PT TDLUs within subjects demonstrated that ER levels were significantly lower in premenopausal women vs. postmenopausal women (odds ratio [OR]=0.38, 95% confidence interval [CI]=0.19, 0.76, P=0.0064) and among recent or current menopausal hormone therapy users compared with never users (OR=0.14, 95% CI=0.046–0.43, Ptrend=0.0006). Compared with premenopausal women, TDLUs of postmenopausal women showed lower levels of PR (OR=0.90, 95% CI=0.83–0.97, Ptrend=0.007). ER and PR expression in TDLUs was associated with epidermal growth factor receptor (EGFR) expression in invasive tumors (P=0.019 for ER and P=0.03 for PR), but not with other tumor features. Conclusions Our data suggest that TDLUs near breast cancers reflect field effects, whereas those at a distance demonstrate influences of breast

  8. Prescription of Chinese herbal products is associated with a decreased risk of invasive breast cancer

    Science.gov (United States)

    Tsai, Yueh-Ting; Lai, Jung-Nien; Lo, Pei-Chia; Chen, Chin-Nu; Lin, Jaung-Geng

    2017-01-01

    Abstract The finding of a decrease in endometrial cancer incidence among breast cancer survivors following the use of Chinese herbal products (CHPs) has led to speculation that CHPs might play a role in breast cancer prevention. This study provides an overview of breast cancer incidence, comparing CHP users with those who do not use traditional Chinese medicine (TCM), referred to as non-TCM users. The results can provide information to clinicians for counseling women about the preventive use of TCM. A total of 184,386 women (20–79 years of age) were recruited from a nationwide 1-million-person representative sample of those covered by National Health Insurance in Taiwan and were followed from 1999 to 2012. A total of 1853 incidents of invasive breast cancer were diagnosed. The person-year approach with the Poisson assumption was used to estimate the incidence density rate. The age-specific hazard ratios of breast cancer in relation to either CHP or siwutang (SWT) use were calculated with multivariate Cox proportional hazard regression. More than 78% of patients had used a CHP at some point previously. The overall incidence density rate of breast cancer for non-TCM users was estimated at 1.73 per 10,000 patient-years. The corresponding values for CHP and SWT users were lower than those of the non-TCM group (CHP group = 0.85; SWT group = 0.63 per 10,000 patient-years). The covariate adjusted HRs for breast cancer were 0.57 (95% confidence interval [CI] 0.50–0.65) and 0.36 (95% CI 0.28–0.46) in women using CHPs and SWT, respectively. The findings were confirmed using propensity score matching. Consumption of CHPs reduces the incidence of invasive breast cancer. Although the mechanism of action of these products is unclear, their use as a preventive agent for breast cancer is appropriate for many women at an increased risk of breast cancer. PMID:28858112

  9. Mixed Lineage Kinase3 as a Novel Target for Invasive Breast Cancer

    Science.gov (United States)

    2013-04-01

    myeloid M1 cell line. J Cell Biochem 86: 1–11. Hanahan D, Weinberg RA. (2000). The hallmarks of cancer. Cell 100: 57–70. Jacinto A, Woolner S, Martin P...papillomavirus E7 repression in cervical carcinoma cells initiates a transcriptional cascade driven by the retinoblastoma family, resulting in...axis induces expression of several breast cancer invasion genes (16). The mechanics of cancer cell migration involve cytoskeletal remodeling and focal

  10. Curcumin inhibition of integrin (alpha6beta4)-dependent breast cancer cell motility and invasion.

    Science.gov (United States)

    Kim, Hong Im; Huang, Huang; Cheepala, Satish; Huang, Shile; Chung, Jun

    2008-10-01

    Curcumin, a polyphenol natural product isolated from the rhizome of the plant Curcuma longa, has emerged as a promising anticancer therapeutic agent. However, the mechanism by which curcumin inhibits cancer cell functions such as cell growth, survival, and cell motility is largely unknown. We explored whether curcumin affects the function of integrin alpha(6)beta(4), a laminin adhesion receptor with an established role in invasion and migration of cancer cells. Here we show that curcumin significantly reduced alpha(6)beta(4)-dependent breast cancer cell motility and invasion in a concentration-dependent manner without affecting apoptosis in MDA-MB-435/beta4 (beta(4)-integrin transfectants) and MDA-MB-231 breast cancer cell lines. Further, curcumin selectively reduced the basal phosphorylation of beta(4) integrin (Y1494), which has been reported to be essential in mediating alpha(6)beta(4)-dependent phosphatidylinositol 3-kinase activation and cell motility. Consistent with this finding, curcumin also blocked alpha(6)beta(4)-dependent Akt activation and expression of the cell motility-promoting factor ENPP2 in MDA-MB-435/beta4 cell line. A multimodality approach using curcumin in combination with other pharmacologic inhibitors of alpha(6)beta(4) signaling pathways showed an additive effect to block breast cancer cell motility and invasion. Taken together, these findings show that curcumin inhibits breast cancer cell motility and invasion by directly inhibiting the function of alpha(6)beta(4) integrin, and suggest that curcumin can serve as an effective therapeutic agent in tumors that overexpress alpha(6)beta(4).

  11. Total RNA Sequencing Analysis of DCIS Progressing to Invasive Breast Cancer

    Science.gov (United States)

    2016-09-01

    for Public Release; Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT: This project is designed to complement a multi-institutional, NIH...the minority of cases of preinvasive breast cancer (DCIS), that do in fact progress to invasive disease (IBC), and complements our multi-institutional...Pathology & Laboratory Medicine Lineberger Comprehensive Cancer Center 125 Mason Farm Road The University of North Carolina at Chapel Hill Chapel

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

    Science.gov (United States)

    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.

  13. FRK inhibits breast cancer cell migration and invasion by suppressing epithelial-mesenchymal transition.

    Science.gov (United States)

    Ogunbolude, Yetunde; Dai, Chenlu; Bagu, Edward T; Goel, Raghuveera Kumar; Miah, Sayem; MacAusland-Berg, Joshua; Ng, Chi Ying; Chibbar, Rajni; Napper, Scott; Raptis, Leda; Vizeacoumar, Frederick; Vizeacoumar, Franco; Bonham, Keith; Lukong, Kiven Erique

    2017-12-22

    The human fyn-related kinase (FRK) is a non-receptor tyrosine kinase known to have tumor suppressor activity in breast cancer cells. However, its mechanism of action has not been fully characterized. We generated FRK-stable MDA-MB-231 breast cancer cell lines and analyzed the effect on cell proliferation, migration, and invasiveness. We also used kinome analysis to identify potential FRK-regulated signaling pathways. We employed both immunoblotting and RT-PCR to identify/validate FRK-regulated targets (proteins and genes) in these cells. Finally, we interrogated the TCGA and GENT gene expression databases to determine the correlation between the expression of FRK and epithelial/mesenchymal markers. We observed that FRK overexpression suppressed cell proliferation, migration, and invasiveness, inhibited various JAK/STAT, MAPK and Akt signaling pathways, and suppressed the expression of some STAT3 target genes. Also, FRK overexpression increased the expression of epithelial markers including E-cadherin mRNA and down-regulated the transcript levels of vimentin, fibronectin, and slug. Finally, we observed an inverse correlation between FRK expression and mesenchymal markers in a large cohort of breast cancer cells. Our data, therefore, suggests that FRK represses cell proliferation, migration and invasiveness by suppressing epithelial to mesenchymal transition.

  14. Cell surface heparan sulfate proteoglycans control adhesion and invasion of breast carcinoma cells

    DEFF Research Database (Denmark)

    Lim, Hooi Ching; Multhaupt, Hinke A. B.; Couchman, John R.

    2015-01-01

    Background: Cell surface proteoglycans interact with numerous regulators of cell behavior through their glycosaminoglycan chains. The syndecan family of transmembrane proteoglycans are virtually ubiquitous cell surface receptors that are implicated in the progression of some tumors, including bre...... syndecan-2, may be important regulators of breast carcinoma progression through regulation of cytoskeleton, cell adhesion and invasion.......Background: Cell surface proteoglycans interact with numerous regulators of cell behavior through their glycosaminoglycan chains. The syndecan family of transmembrane proteoglycans are virtually ubiquitous cell surface receptors that are implicated in the progression of some tumors, including...... breast carcinoma. This may derive from their regulation of cell adhesion, but roles for specific syndecans are unresolved. Methods: The MDA-MB231 human breast carcinoma cell line was exposed to exogenous glycosaminoglycans and changes in cell behavior monitored by western blotting, immunocytochemistry...

  15. SEMA6D Expression and Patient Survival in Breast Invasive Carcinoma

    Directory of Open Access Journals (Sweden)

    Dongquan Chen

    2015-01-01

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

  16. 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.

  17. Increased beta1 integrin is associated with decreased survival in invasive breast cancer.

    Science.gov (United States)

    Yao, Evelyn S; Zhang, Hui; Chen, Yunn-Yi; Lee, Brian; Chew, Karen; Moore, Dan; Park, Catherine

    2007-01-15

    Aberrant microenvironments and loss of balance in cell-extracellular matrix signaling are associated with breast cancer invasion, metastasis, and resistance to therapy. We have recently shown that increased beta1 integrin signaling is involved in malignant progression and that inhibitory antibody to beta1 integrin leads to selective apoptosis and decreased proliferation in three-dimensional cultures and in xenograft models of breast cancer in vivo. To investigate the clinical importance of these findings, in the present study we examined the expression of beta1 integrin and extracellular beta1 integrin ligands fibronectin and laminin-1 in a cohort of 249 breast cancer patients who had a median follow-up of 8.4 years. Among the 149 scorable cases, the highest beta1 integrin intensity score (3+ versus 0-2+) was associated with significantly decreased 10-year overall survival of 48% versus 71% (Pintegrin intensity score was significantly correlated with fibronectin expression (Kendall's tau-b=0.19; P=0.03). In a multivariate Cox proportional hazards model, beta1 integrin intensity score remained a significant independent predictor of overall survival [hazard ratio (HR), 1.69; 95% confidence interval (95% CI), 1.19-2.38; Pintegrin expression has potential prognostic value in invasive breast cancer and that coexpression of fibronectin may help identify patients with more aggressive tumors who may benefit from targeted therapy.

  18. Prognostic Value of MammaPrint® in Invasive Lobular Breast Cancer.

    Science.gov (United States)

    Beumer, Inès J; Persoon, Marion; Witteveen, Anke; Dreezen, Christa; Chin, Suet-Feung; Sammut, Stephen-John; Snel, Mireille; Caldas, Carlos; Linn, Sabine; van 't Veer, Laura J; Bernards, Rene; Glas, Annuska M

    2016-01-01

    MammaPrint® is a microarray-based gene expression test cleared by the US Food and Drug Administration to assess recurrence risk in early-stage breast cancer, aimed to guide physicians in making neoadjuvant and adjuvant treatment decisions. The increase in the incidence of invasive lobular carcinomas (ILCs) over the past decades and the modest representation of ILC in the MammaPrint development data set calls for a stratified survival analysis dedicated to this specific subgroup. The current study aimed to validate the prognostic value of the MammaPrint test for breast cancer patients with early-stage ILCs. Univariate and multivariate survival associations for overall survival (OS), distant metastasis-free interval (DMFI), and distant metastasis-free survival (DMFS) were studied in a study population of 217 early-stage ILC breast cancer patients from five different clinical studies. A significant association between MammaPrint High Risk and poor clinical outcome was shown for OS, DMFI, and DMFS. A subanalysis was performed on the lymph node-negative study population. In the lymph node-negative study population, we report an up to 11 times higher change in the diagnosis of an event in the MammaPrint High Risk group. For DMFI, the reported hazard ratio is 11.1 (95% confidence interval = 2.3-53.0). Study results validate MammaPrint as an independent factor for breast cancer patients with early-stage invasive lobular breast cancer. Hazard ratios up to 11 in multivariate analyses emphasize the independent value of MammaPrint, specifically in lymph node-negative ILC breast cancers.

  19. Prolactin signaling stimulates invasion via Na+/H+ exchanger NHE1 in T47D human breast cancer cells

    DEFF Research Database (Denmark)

    Pedraz Cuesta, Elena; Fredsted, Jacob; Jensen, Helene H.

    2016-01-01

    Prolactin (PRL) and its receptor the PRLR are implicated in breast cancer invasiveness, although their exact roles remain controversial. The Na(+)/H(+) exchanger NHE1 plays essential roles in cancer cell motility and invasiveness, but the PRLR and NHE1 have not previously been linked. Here, we show...

  20. IGF-1 regulates Cyr61 induced breast cancer cell proliferation and invasion.

    Directory of Open Access Journals (Sweden)

    Suren Sarkissyan

    Full Text Available Studies from our laboratory and others have shown that cysteine-rich 61 (Cyr61 may be involved in tumor proliferation and invasion. In earlier studies, we demonstrated increased insulin-like growth factor-I (IGF-1 is associated with breast tumor formation and poor clinical outcomes. In our current study we have investigated IGF-1 regulation of Cyr61 and whether targeting IGF-1 could inhibit Cyr61 induced tumor growth and proliferation.Several ATCC derived normal and breast cancer cell lines were used in this study: MDA-MB231, BT474, MCF-7, and SKBR3. We also tested cells stably transfected in our laboratory with active Akt1 (pAkt; SKBR3/AA and MCF-7/AA and dominant negative Akt1 (SKBR3/DN and MCF-7/DN. In addition, we used MCF-7 cells transfected with full length Cyr61 (CYA. Monolayer cultures treated with IGF-1 were analyzed for Cyr61 expression by RT-PCR and immunohistochemical staining. Migration assays and MTT based proliferation assays were used to determine invasive characteristics in response to IGF-1/Cyr61 activation.Cells with activated Akt have increased levels of Cyr61. Conversely, cells with inactive Akt have decreased levels of Cyr61. IGF-1 treatment increased Cyr61 expression significantly and cells with high level of Cyr61 demonstrate increased invasiveness and proliferation. Cyr61 overexpression and activation led to decrease in E-cadherin and decrease in FOXO1. Inhibition of the PI3K and MAPK pathways resulted in significant decrease in invasiveness and proliferation, most notably in the PI3K pathway inhibited cells.The findings of this study show that IGF-1 upregulates Cyr61 primarily through activation of the Akt-PI3K pathway. IGF-1 induced MAPK plays a partial role. Increase in Cyr61 leads to increase in breast cancer cell growth and invasion. Hence, targeting Cyr61 and associated pathways may offer an opportunity to inhibit IGF-1 mediated Cyr61 induced breast cancer growth and invasion.

  1. PTH-related protein enhances MCF-7 breast cancer cell adhesion, migration, and invasion via an intracrine pathway.

    Science.gov (United States)

    Shen, Xiaoli; Qian, Lihui; Falzon, Miriam

    2004-04-01

    Breast cancer is the most common carcinoma that metastasizes to the bone. Parathyroid hormone-related protein (PTHrP), a known stimulator of osteoclastic bone resorption, is a major mediator of the osteolytic process in breast cancer. PTHrP overexpression increases mitogenesis and decreases apoptosis in the human breast cancer cell line MCF-7. In this study, MCF-7 cells were used as a model system to study the effects of PTHrP on breast cancer cell adhesion, migration, and invasion. Clones of MCF-7 cells were established that overexpress wild-type PTHrP or PTHrP mutated in the nuclear localization sequence (NLS). Wild-type PTHrP-overexpressing cells showed significantly higher laminin adhesion and migration, and Matrigel invasion than empty vector-transfectants or cells overexpressing NLS-mutated PTHrP. Wild-type PTHrP also increased the cell surface expression of the pro-invasive integrins alpha6 and beta4; deletion of the NLS negated these effects. Exogenous PTHrP (1-34), (67-86), (107-139), and (140-173) had no effect on integrin expression, or on cell adhesion, migration, and invasion. These results indicate that PTHrP exerts its effects on cell adhesion, migration, invasion, and integrin expression via an intracrine pathway. PTHrP may play a role in breast cancer metastasis by upregulating proinvasive integrin expression, and controlling PTHrP production in breast cancer may provide therapeutic benefit.

  2. A Cost Analysis of Preoperative Breast MRI Use for Patients with Invasive Lobular Cancer.

    Science.gov (United States)

    Bedrosian, Isabelle; Xing, Yan; Abdel Rahman, Shereen; Allen, Lisa; Le-Petross, Huong; Whitman, Gary J; Meric-Bernstam, Funda; Hunt, Kelly K; Babiera, Gildy V; Cormier, Janice N

    2016-01-01

    Whereas the impact of magnetic resonance imaging (MRI) of the breast on the surgical management of breast cancer patients is well documented, less is known about its effect on health care costs. This study aimed to evaluate whether MRI use for women with invasive lobular carcinoma (ILC) significantly changes the cost of care. Patients with ILC were recruited to a prospective registry study of breast MRI. Women who met the same inclusion criteria but had not undergone breast MRI were retrospectively identified for comparison. A micro-costing analysis using institutional billing records was conducted. Nonparametric bootstrapping was used to compare the unadjusted cost differences between the patients receiving MRI and those receiving no MRI. Of the patients in this study, 51 had preoperative MRI, and 60 did not. Method of diagnostic biopsy, disease stage, oncologic procedure, and rates of contralateral prophylactic mastectomy were similar between the two groups. The patients in the MRI group were younger (median age 55 vs. 64 years; p = 0.01) and more likely to undergo reconstruction (45.1 vs. 25 %; p = 0.03). The median costs of care were significantly higher in the MRI group ($24,781 vs. $18,921; p 1; p < 0.01), and use of reconstruction (p < 0.01). Preoperative breast MRI increases the median total cost of care per patient. However, the contribution to the overall cost of care is modest compared with the cost of other interventions.

  3. Myiasis associated with an invasive ductal carcinoma of the left breast: case study

    Directory of Open Access Journals (Sweden)

    Felipe Tavares Rodrigues

    Full Text Available ABSTRACT Most breast cancers originate in the ductal epithelium and are referred to as invasive ductal carcinoma. In this study we report on the clinical procedures adopted to diagnose myiasis in association with infiltrating metastatic breast carcinoma in a female patient. A 41 years old woman came to the Federal Hospital of Andaraí complaining of intense itching, warmth, redness and hardening of the breast, which had acquired the aspect of an orange peel. A lesion in the left breast was cavitated, dimpled, had fetid odor, and had fibrotic and infected air nodules filled with exudate and Dipteran larvae. The tissue was cleaned and 33 larvae were extracted. The patient was hospitalized and received Ivermectin. Eighteen of the larvae extracted from the patient were placed in 70% alcohol, and twelve were placed in a container with sterile wood shavings under controlled conditions until they metamorphosed into adults. The taxonomic identification of the flies revealed that the culprit was Cochliomyia hominivorax. A histopathological exam conducted three months earlier had revealed infiltrating ductal carcinoma. Two months after the myiasis treatment, the breast tissue had healed. The patient had waited ten days from the onset of the myiasis to seek treatment, and that delay interfered negatively in the prognosis of both the neoplasm and the myiasis. This study is relevant to public health in view of the strong social impact of myiasis.

  4. The role of angiotensin II in the regulation of breast cancer cell adhesion and invasion.

    Science.gov (United States)

    Puddefoot, J R; Udeozo, U K I; Barker, S; Vinson, G P

    2006-09-01

    As breast cancer remains the most common cause of cancer death in women, there is a continuing need not only to further characterise the processes of cancer progression, but also to improve accuracy of prognostic markers. Breast epithelial cells express components of the renin angiotensin system and studies suggest that these may be altered in disease progression. In addition, altered integrin expression correlates with lymph node metastasis. The aim of this study was to investigate the relationship between angiotensin II (AII) and integrins in breast tissue and, in particular, their role in breast cancer cell metastasis. Using in vitro assays, AII (10(-6) M)-treated MCF-7 and T47D breast cancer cells both show reduced adhesion to extracellular matrix proteins collagen-, fibronectin- and laminin-coated wells (Plaminin-coated membranes (Pintegrin alpha3 and beta1. Using specific inhibitors, this was shown to occur through protein kinase C signalling. These data suggest that AII reduces cell adhesion and invasion through the type 1 receptor and that this effect may be due to reduced expression of integrins, and in particular alpha3 and beta1.

  5. VI-14, a novel flavonoid derivative, inhibits migration and invasion of human breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Li, Fanni; Li, Chenglin; Zhang, Haiwei; Lu, Zhijian [State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009 (China); Li, Zhiyu; You, Qidong [Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009 (China); Lu, Na [State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009 (China); Guo, Qinglong, E-mail: anticancer_drug@yahoo.com.cn [State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009 (China)

    2012-06-01

    It has been well characterized that flavonoids possess pronounced anticancer potentials including anti-angiogenesis, anti-metastasis, and pro-apoptosis. Herein, we report, for the first time, that VI-14, a novel flavonoid derivative, possesses anti-cancer properties. The purpose of this study is to investigate the anti-migration and anti-invasion activities of VI-14 in breast cancer cells. Our data indicate that VI-14 inhibits adhesion, migration and invasion of MDA-MB-231 and MDA-MB-435 human breast cancer cells. MDA-MB-231 cells treated with VI-14 display reduced activities and expressions of ECM degradation-associated proteins including matrix metalloproteinase 2 (MMP-2) and 9 (MMP-9) at both the protein and mRNA levels. Meanwhile, VI-14 treatment induces an up-regulated expression of tissue inhibitor of metalloproteinase 1 (TIMP-1) and 2 (TIMP-2) in MDA-MB-231 cells. Western blotting results show that phosphorylation levels of critical components of the MAPK signaling pathway, including ERK, JNK and P38, are dramatically decreased in VI-14-treated MDA-MB-231 cells. Furthermore, treatment of VI-14 significantly decreases the nuclear levels and the binding ability of nuclear factor-kappa B (NF-κB) and activator protein-1 (AP-1). Taken together, our data suggest that VI-14 treatment suppresses migration and motility of breast cancer cells, and VI-14 may be a potential compound for cancer therapy. Highlights: ► We report for the first time that VI-14 possesses anti-cancer properties. ► VI-14 weakens the adhesion, migration and invasion of human breast cancer cells. ► VI-14 decreases the activities and expressions of MMP-2/9. ► VI-14 suppresses the phosphorylation levels of the MAPK signaling pathway. ► VI-14 decreases the nuclear levels and the binding ability of NF-κB and AP-1.

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

    International Nuclear Information System (INIS)

    Pavlakis, Kitty; Messini, Irene; Vrekoussis, Thomas; Yiannou, Petros; Keramopoullos, Dimitrios; Louvrou, Niki; Liakakos, Theodoros; Stathopoulos, Efstathios N

    2008-01-01

    To investigate the changes of the neoplastic microenvironment during the different morphological alterations of hyperplastic and pre-invasive breast lesions. 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. VEGF expression was strongly correlated with MVD in all hyperplastic and pre-invasive breast lesions (p < 0.05). Stromagenesis, as characterized by an increase in SMA and a decrease in CD34 positive myofibroblasts was observed mostly around ducts harboring high grade in situ carcinoma and to a lesser extent around moderately differentiated DCIS. In these two groups of in situ carcinomas, a positive correlation between MVD and SMA (p < 0.05) was observed. On the contrary, CD34 was found to be inversely related to MVD (p < 0.05). No statistically significant changes of the stromal fibroblasts were observed in low grade DCIS neither in any of the other lesions under investigation as compared to normal mammary intra- and interlobular stroma. 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

  7. Non-Invasive In Vivo Characterization of Breast Tumors Using Photon Migration Spectroscopy

    Directory of Open Access Journals (Sweden)

    Bruce J. Tromberg

    2000-01-01

    Full Text Available Frequency-domain photon migration (FDPM is a noninvasive optical technique that utilizes intensity-modulated, near-infrared (NIR light to quantitatively measure optical properties in thick tissues. Optical properties (absorption, μa, and scattering, μs′, parameters derived from FDPM measurements can be used to construct low-resolution (0.5 to 1 cm functional images of tissue hemoglobin (total, oxy-, and deoxyforms, oxygen saturation, blood volume fraction, water content, fat content and cellular structure. Unlike conventional NIR transillumination, FDPM enables quantitative analysis of tissue absorption and scattering parameters in a single non-invasive measurement. The unique functional information provided by FDPM makes it well-suited to characterizing tumors in thick tissues. In order to test the sensitivity of FDPM for cancer diagnosis, we have initiated clinical studies to quantitatively determine normal and malignant breast tissue optical and physiological properties in human subjects. Measurements are performed using a non-invasive, multi-wavelength, diode-laser FDPM device optimized for clinical studies. Results show that ductal carcinomas (invasive and in situ and benign fibroadenomas exhibit 1.25 to 3-fold higher absorption than normal breast tissue. Within this group, absorption is greatest for measurements obtained from sites of invasive cancer. Optical scattering is approximately 20% greater in pre-menopausal versus post-menopausal subjects due to differences in gland/cell proliferation and collagen/fat content. Spatial variations in tissue scattering reveal the loss of differentiation associated with breast disease progression. Overall, the metabolic demands of hormonal stimulation and tumor growth are detectable using photon migration techniques. Measurements provide quantitative optical property values that reflect changes in tissue perfusion, oxygen consumption, and cell/matrix development.

  8. Mammographic, sonographic and MR imaging features of invasive micropapillary breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Alsharif, Shaza; Daghistani, Razan; Kamberoğlu, Elif Aşik; Omeroglu, Atilla; Meterissian, Sarkis; Mesurolle, Benoît, E-mail: benoit.mesurolle@muhc.mcgill.ca

    2014-08-15

    Purpose: Describe mammographic, sonographic and MRI findings of invasive micropapillary carcinoma (IMPC) of the breast. Materials and methods: Review of the pathology database identified 43 patients (mean age, 59.3 years) with the diagnosis of breast IMPC. Three patients had no available imaging studies. Mammograms (40), breast ultrasounds (33) and MRIs (8) were retrospectively evaluated by two radiologists in consensus following the BI-RADS Lexicon. Clinical, histopathologic features, as well as hormone status were recorded. Results: Twenty patients presented with palpable abnormality (20/40, 50%). Thirty-five patients had an abnormal mammogram (87.5%, 35/40) showing 39 lesions, 29 corresponding to masses (29/39, 74.4%), 11 associated with microcalcifications and two associated with architectural distortion. Sonography identified 41 masses (in 33 patients) displaying an irregular shape (30/41, 73.2%), appearing hypoechoic (39/41, 95%), with spiculated or angular margins (26/41, 63.4%), non-parallel orientation (26/41, 63.4%) and combined acoustic posterior pattern (18/41, 44%). MRI identified 13 lesions (in eight patients), 12 as masses (12/13, 92.3%) with irregular or spiculated margins (12/12, 100%), eight displaying an irregular or lobulated shape (8/12, 66.7%), six with homogeneous internal enhancement (6/12, 50%) and eight with type 3 enhancement curve (8/12, 61.5%). Associated non-mass like enhancement was noted in two patients. Twenty-nine patients had associated lymphovascular invasion (29/40, 72.5%) and axillary lymph node metastases were present in 22 of the 39 patients (22/39, 56%). Conclusion: Invasive ductal carcinoma with IMPC features display imaging findings highly suspicious of malignant lesions. They are associated with high lymphovascular invasion and lymph node metastases rates.

  9. 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

  10. Physiological COX-2 Expression in Breast Epithelium Associates with COX-2 Levels in Ductal Carcinoma in Situ and Invasive Breast Cancer in Young Women

    Science.gov (United States)

    Fornetti, Jaime; Jindal, Sonali; Middleton, Kara A.; Borges, Virginia F.; Schedin, Pepper

    2015-01-01

    Cyclooxygenase-2 (COX-2) overexpression is implicated in increased risk and poorer outcomes in breast cancer in young women. We investigated COX-2 regulation in normal premenopausal breast tissue and its relationship to malignancy in young women. Quantitative COX-2 immunohistochemistry was performed on adjacent normal and breast cancer tissues from 96 premenopausal women with known clinical reproductive histories, and on rat mammary glands with distinct ovarian hormone exposures. COX-2 expression in the normal breast epithelium varied more than 40-fold between women and was associated with COX-2 expression levels in ductal carcinoma in situ and invasive cancer. Normal breast COX-2 expression was independent of known breast cancer prognostic indicators, including tumor stage and clinical subtype, indicating that factors regulating physiological COX-2 expression may be the primary drivers of COX-2 expression in breast cancer. Ovarian hormones, particularly at pregnancy levels, were identified as modulators of COX-2 in normal mammary epithelium. However, serial breast biopsy analysis in nonpregnant premenopausal women suggested relatively stable baseline levels of COX-2 expression, which persisted independent of menstrual cycling. These data provide impetus to investigate how baseline COX-2 expression is regulated in premenopausal breast tissue because COX-2 levels in normal breast epithelium may prove to be an indicator of breast cancer risk in young women, and predict the chemopreventive and therapeutic efficacy of COX-2 inhibitors in this population. PMID:24518566

  11. Epidemiology and patterns of care for invasive breast carcinoma at a community hospital in Southern India

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    Venkata Phanindra

    2007-05-01

    Full Text Available Abstract Background Breast cancer incidence in India is on rise. We report epidemiological, clinical and survival patterns of breast cancer patients from community perspective. Methods All breast cancer patients treated at this hospital from July 2000 to July 2005 were included. All had cytological or histological confirmation of breast cancer. TNM guidelines for staging and Immunohistochemistry to assess the receptor status were used. Either lumpectomy with axillary lymph node dissection or Modified radical mastectomy (MRM was done for operable breast cancer, followed by 6 cycles of adjuvant chemotherapy with FAC or CMF regimens to patients with pT >1 cm or lymph node positive or estrogen receptor negative and radiotherapy to patients after breast conservation surgery, pT size > 5 cm, 4 or more positive nodes and stage IIIB disease. Patients with positive Estrogen receptor or Progesterone receptor were advised Tamoxifene 20 mg per day for 3 years. Descriptive analysis was performed. Independent T test and Chi-square test were used. Overall survival time was computed by Kaplan – Meier method. Results Of 1488 cancer patients, 122 (8.2% had breast cancer. Of 122 patients, 96.7% had invasive breast carcinoma and 3.3% had sarcoma. 94% came from the rural and semi urban areas. Premenopausal women were 27%. The median age was 50 years. Stage I-6.8%, II-45.8%, III-22%, IV-6.8%, Bilateral breast cancer – 2.5%. The mean pT size was 3.9 cm. ER and PR were positive in 31.6% and 28.1% respectively. MRM was done in 93.8%, while 6.3% patients underwent breast conservation surgery. The mean of the lymph nodes dissected were 3. CMF and FAC regimens were used in 48.8% and 51.2% of patients respectively. FAC group were younger than the CMF group (43.6 yr vs. 54 yrs, P = 0.000. Toxicities were more in FAC than CMF group, alopecia (100% vs. 26.2%, grade2 or more emesis (31.8% vs. 9.2%, grade2 or more fatigue (40.9% vs.19%, anemia (43.1% vs. 16.6%. Median

  12. Prospective Clinical Trial of 18F-Fluciclovine PET/CT for Determining the Response to Neoadjuvant Therapy in Invasive Ductal and Invasive Lobular Breast Cancers.

    Science.gov (United States)

    Ulaner, Gary A; Goldman, Debra A; Corben, Adriana; Lyashchenko, Serge K; Gönen, Mithat; Lewis, Jason S; Dickler, Maura

    2017-07-01

    18 F-labeled 1-amino-3-fluorocyclobutane-1-carboxylic acid ( 18 F-fluciclovine) is a leucine analog radiotracer that depicts amino acid transport into cells. 18 F-fluciclovine PET/CT visualizes malignancy, including prostate cancer, invasive ductal breast cancer, and invasive lobular breast cancer. Whether changes in 18 F-fluciclovine avidity reflect changes in tumor burden resulting from treatment has not been shown. In this prospective clinical trial (clinical trials.gov: NCT01864083), changes in 18 F-fluciclovine avidity after neoadjuvant therapy were compared to breast cancer therapy response, as determined by residual tumor burden on pathology, were evaluated. Methods: Twenty-four women with a new diagnosis of locally advanced invasive ductal breast cancer ( n = 18) or invasive lobular breast cancer ( n = 6) underwent 18 F-fluciclovine PET/CT before and after the completion of neoadjuvant systemic therapy. SUV max , SUV mean , metabolic tumor volume, and total lesion avidity were obtained for the primary breast tumor, axillary lymph nodes, and extraaxillary lymph nodes on each examination and corrected for background 18 F-fluciclovine avidity. The relationship between changes in 18 F-fluciclovine avidity and the percentage of reduction of tumor on pathology was assessed with the Spearman rank correlation. Results: The median decrease in the corrected SUV max of the primary breast lesions was 99% (range, 33%-100%). The median reduction of tumor on pathology was 92% (range, 10%-100%). Changes in 18 F-fluciclovine avidity were strongly correlated with the percentage of reduction of tumor on pathology (Spearman ρ, 0.79; 95% CI, 0.56-0.90; P < 0.001). Conclusion: Changes in 18 F-fluciclovine avidity strongly correlated with the tumor response on pathology in this pilot study. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

  13. Chapter 27 -- Breast Cancer Genomics, Section VI, Pathology and Biological Markers of Invasive Breast Cancer

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    Spellman, Paul T.; Heiser, Laura; Gray, Joe W.

    2009-06-18

    Breast cancer is predominantly a disease of the genome with cancers arising and progressing through accumulation of aberrations that alter the genome - by changing DNA sequence, copy number, and structure in ways that that contribute to diverse aspects of cancer pathophysiology. Classic examples of genomic events that contribute to breast cancer pathophysiology include inherited mutations in BRCA1, BRCA2, TP53, and CHK2 that contribute to the initiation of breast cancer, amplification of ERBB2 (formerly HER2) and mutations of elements of the PI3-kinase pathway that activate aspects of epidermal growth factor receptor (EGFR) signaling and deletion of CDKN2A/B that contributes to cell cycle deregulation and genome instability. It is now apparent that accumulation of these aberrations is a time-dependent process that accelerates with age. Although American women living to an age of 85 have a 1 in 8 chance of developing breast cancer, the incidence of cancer in women younger than 30 years is uncommon. This is consistent with a multistep cancer progression model whereby mutation and selection drive the tumor's development, analogous to traditional Darwinian evolution. In the case of cancer, the driving events are changes in sequence, copy number, and structure of DNA and alterations in chromatin structure or other epigenetic marks. Our understanding of the genetic, genomic, and epigenomic events that influence the development and progression of breast cancer is increasing at a remarkable rate through application of powerful analysis tools that enable genome-wide analysis of DNA sequence and structure, copy number, allelic loss, and epigenomic modification. Application of these techniques to elucidation of the nature and timing of these events is enriching our understanding of mechanisms that increase breast cancer susceptibility, enable tumor initiation and progression to metastatic disease, and determine therapeutic response or resistance. These studies also

  14. Female breast cancer in Świętokrzyskie Voivodeship in 1999–2012. New cases and the incidence of invasive breast cancer

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    Ewa Błaszkiewicz

    2015-07-01

    Full Text Available Introduction : Breast cancer is the most common malignant tumour among women in Poland. In 2012 invasive breast cancer was diagnosed in 17,000 Polish women. The effective fight against breast cancer is based on activities to prevent its occurrence or to enable early detection of the disease and then its effective treatment (cure. Aim of the research: To assess the prevalence of invasive breast cancer in women in Świętokrzyskie Voivodeship in 1999–2012. Material and methods: A total of 6079 new female invasive breast cancer cases were analysed. Crude rates (CRs and age-standarised rates (ASRs per 100,000 population were calculated. The total value of incidence rates was analysed for all ages (0–85+ and in separate age groups (15–49, 50–69, and 70–85+. Results : In 1999–2012 in Świętokrzyskie Voivodeship 6079 new invasive female breast cancer cases were diagnosed. Fifty-three percent of them were in the age group of 50–69 years, 25.0% in the age group 70–85+, and 21.5% in the age group 15–49 years. The incidence of BC in general (0–85+ increased from 41.2/105 in 1999 to 43.8/105 in 2012. In the women aged 15–49 years the value of ASRs of incidence increased. In the age group of 50–69 years the value of ASRs increased from 146.6/105 in 1999 to 163.5/105 in 2012. The increase in the incidence of breast cancer was reported among women in perimenopausal age and in premenopausal women. The decrease in breast cancer cases was observed among young, premenopausal women (15–49 years as well as among women over 70 years of age. Conclusions: Świętokrzyskie Voivodeship is a region in Poland with moderate risk of breast cancer.

  15. An Analysis of Oncotype DX Recurrence Scores and Clinicopathologic Characteristics in Invasive Lobular Breast Cancer.

    Science.gov (United States)

    Felts, Jesse L; Zhu, Junjia; Han, Bing; Smith, Stanley J; Truica, Cristina I

    2017-11-01

    The Oncotype DX breast cancer assay (Genomic Health, Redwood City, CA) is increasingly being used to guide treatment decisions for patients with early stage, hormone-positive, Her-2-negative breast cancer. The utility of the Oncotype DX in decision making for treatment of invasive lobular carcinoma (ILC) has not been investigated as the results reported by Genomic Health are largely in a population with invasive ductal carcinoma (IDC). The authors hypothesized that the Oncotype DX recurrence score (RS) distribution for ILC is different than that for IDC. We performed a retrospective analysis of early stage breast cancer patients treated at Penn State Cancer Institute from 2001 to 2011 and identified 102 patients with ILC. We also pulled RS data from our institution's prospective registry of consecutive patients with early stage IDC treated during the same time period. Median follow-up was 55 months. We found that the RS distribution for ILC differed significantly from that of IDC (p = 0.024). We also found a statistically significant difference in the RS distribution between the pure ILC and pleomorphic ILC subtypes (p = 0.027). The Oncotype DX RS distribution in ILC is unique, differing significantly from that in ductal carcinoma. Consequently, the clinical usefulness and cost-effectiveness of the Oncotype DX in guiding treatment for ILC should be further investigated. © 2017 Wiley Periodicals, Inc.

  16. Effect of adjuvant chemotherapy in postmenopausal patients with invasive ductal versus lobular breast cancer.

    Science.gov (United States)

    Truin, W; Voogd, A C; Vreugdenhil, G; van der Heiden-van der Loo, M; Siesling, S; Roumen, R M

    2012-11-01

    On the basis of the lack of response of invasive lobular breast cancer to neoadjuvant chemotherapy, we questioned the effectiveness of adjuvant chemotherapy in relation to histology. Women with primary nonmetastatic invasive ductal or (mixed type) lobular breast cancer, aged 50-70 years, diagnosed between 1995 and 2008, were selected from the Netherlands Cancer Registry and followed until January 1, 2010. The patients were divided in two groups: one group receiving adjuvant hormonal therapy only and the other receiving adjuvant hormonal therapy in combination with adjuvant chemotherapy. In total, 19,609 patients had ductal cancer and 3685 had lobular cancer. The 10-year overall survival rate in ductal cancer when treated with hormonal therapy alone was 69%, compared with 74% with the combination therapy (P lobular cancer, 10-year survival rates were 68% after hormonal treatment alone and 66% after the combination therapy (P = 0.45). The hazard ratio (HR) for mortality in ductal cancer after combination therapy was 0.70 [95% confidence interval (CI) 0.64-0.76; P lobular cancer was 1.00 (95% CI 0.82-1.21; P = 0.97). Adjuvant chemotherapy seems to confer no additional beneficial effects in postmenopausal patients with pure or mixed type lobular breast cancer receiving hormonal therapy.

  17. 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.

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

    International Nuclear Information System (INIS)

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

    2008-01-01

    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). 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. 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. Tumor-derived, but not stromal fibroblast-derived, MMP-13 correlated with aggressive tumor phenotypes, and inversely correlated with the

  19. 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.

  20. Nipple-sparing Mastectomy in Patients with Preoperative Diagnosis of Non-invasive Breast Carcinoma. A Single-center Experience.

    Science.gov (United States)

    Amabile, Maria Ida; Monti, Massimo; Merola, Raffaele; Frusone, Federico; D'Orazi, Valerio; Pasta, Vittorio

    2016-02-01

    Nipple-sparing mastectomy (NSM) is a recognized treatment for selected patients with breast cancer (BC). Our study aimed to analyze 7 years' experience in NSM and breast reconstruction for patients with preoperative diagnosis of non-invasive BC. All NSMs with breast reconstruction, performed between January 2007 and December 2013 in patients with preoperative diagnosis of non-invasive BC, were considered. Thirty-five NSMs were performed, 23 cases confirming the diagnosis of non-invasive BC, and in 12 patients it also resulted in findings of an invasive component. Patients were stratified into two groups: breast reconstruction was performed i) with silicone definitive implant, ii) with a temporary breast tissue expander. An invasive component at the postoperative histological examination was significantly associated with tissue expander reconstruction (p=0.03). In selected cases, NSM is a valid and safe procedure. Further critical evaluations are required for more evidence on this argument. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  1. The influence of aging on pathologic and immunobiologic parameters of invasive ductal breast carcinoma

    Directory of Open Access Journals (Sweden)

    Ivković-Kapicl Tatjana

    2006-01-01

    Full Text Available Background/Aim. Most human cancers, including breast one, increase in frequency with aging. The aim of this study was to explore the hypothesis that aging also alters breast cancer biology. Methods. The study included 120 women with primary invasive ductal carcinoma of the breast. We correlated the patients age and diagnosis with the commonly used clinical, pathological factors and newer tumor biomarkers. Immunohistochemical staining was conducted for p53, c-erbB-2, Ki-67, estrogen (ER, progesterone (PR receptors, and angiogenesis. Results. In our study, the patients with axillary lymph node metastases and negative steroid hormone receptors (ER and PR were significantly younger than the patients with nodal involvement and positive hormone receptors. There was also a significant association between the patients age, diagnosis and angiogenesis. No association was found between the patients age and tumor size, histological grade, p53, c-erbB-2, and Ki-67. Conclusion. The results of our study supported only partially the hypothesis that the breast cancer biology is significantly affected by a patient's age.

  2. Computer-aided-detection marker value and breast density in the detection of invasive lobular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Destounis, Stamatia; Hanson, Sarah [The Elizabeth Wende Breast Clinic, Rochester, NY (United States); Roehrig, Jimmy [R2/Hologic, Inc., Santa Clara, CA (United States)

    2007-08-15

    Invasive Lobular Carcinoma (ILC) is frequently a mammographic and diagnostic dilemma; thus any additional information that CAD (Computer-Aided Detection) systems can give radiologists may be helpful. Our study was to evaluate the role of CAD numeric values as indicators of malignancy and the effect of breast density in the diagnosis of ILC. Eighty consecutive biopsy-proven ILC cases with CAD (ImageChecker {sup registered}, Hologic vertical stroke R2, Santa Clara, CA, versions 2.3, 3.1, 3.2, 5.0, 5.2) diagnosed between June 2002 and December 2004 were retrospectively reviewed. Data included: BIRADS {sup registered} breast density, whether CAD marked the cancer at diagnosis year or years prior, and lesion type. Study mammograms underwent additional CAD scans (Image Checker {sup registered} V5.3, V8.0, V8.1) to obtain a numeric value associated with each marker, low values represent increasingly suspicious features. CAD correctly marked 65% (52/80) of ILC cases, detection was found to decrease with increased breast density. Numeric values of CAD marks at sites of carcinoma showed median score of 171 (range 0 - 1121). The CAD marker may potentially be used as an additional indicator of suspicious lesion features in all breast densities and higher likelihood that an area on the mammogram requires further investigation. (orig.)

  3. Computer-aided-detection marker value and breast density in the detection of invasive lobular carcinoma

    International Nuclear Information System (INIS)

    Destounis, Stamatia; Hanson, Sarah; Roehrig, Jimmy

    2007-01-01

    Invasive Lobular Carcinoma (ILC) is frequently a mammographic and diagnostic dilemma; thus any additional information that CAD (Computer-Aided Detection) systems can give radiologists may be helpful. Our study was to evaluate the role of CAD numeric values as indicators of malignancy and the effect of breast density in the diagnosis of ILC. Eighty consecutive biopsy-proven ILC cases with CAD (ImageChecker registered , Hologic vertical stroke R2, Santa Clara, CA, versions 2.3, 3.1, 3.2, 5.0, 5.2) diagnosed between June 2002 and December 2004 were retrospectively reviewed. Data included: BIRADS registered breast density, whether CAD marked the cancer at diagnosis year or years prior, and lesion type. Study mammograms underwent additional CAD scans (Image Checker registered V5.3, V8.0, V8.1) to obtain a numeric value associated with each marker, low values represent increasingly suspicious features. CAD correctly marked 65% (52/80) of ILC cases, detection was found to decrease with increased breast density. Numeric values of CAD marks at sites of carcinoma showed median score of 171 (range 0 - 1121). The CAD marker may potentially be used as an additional indicator of suspicious lesion features in all breast densities and higher likelihood that an area on the mammogram requires further investigation. (orig.)

  4. Is Mistletoe Treatment Beneficial in Invasive Breast Cancer? A New Approach to an Unresolved Problem.

    Science.gov (United States)

    Fritz, Peter; Dippon, Jürgen; Müller, Simon; Goletz, Sven; Trautmann, Christian; Pappas, Xenophon; Ott, German; Brauch, Hiltrud; Schwab, Matthias; Winter, Stefan; Mürdter, Thomas; Brinkmann, Friedhelm; Faisst, Simone; Rössle, Susanne; Gerteis, Andreas; Friedel, Godehard

    2018-03-01

    In this retrospective study, we compared breast cancer patients treated with and without mistletoe lectin I (ML-I) in addition to standard breast cancer treatment in order to determine a possible effect of this complementary treatment. This study included 18,528 patients with invasive breast cancer. Data on additional ML-I treatments were reported for 164 patients. We developed a "similar case" method with a distance measure retrieved from the beta variable in Cox regression to compare these patients, after stage adjustment, with their non-ML-1 treated counterparts in order to answer three hypotheses concerning overall survival, recurrence free survival and life quality. Raw data analysis of an additional ML-I treatment yielded a worse outcome (p=0.02) for patients with ML treatment, possibly due to a bias inherent in the ML-I-treated patients. Using the "similar case" method (a case-based reasoning approach) we could not confirm this harm for patients using ML-I. Analysis of life quality data did not demonstrate reliable differences between patients treated with ML-I treatment and those without proven ML-I treatment. Based on a "similar case" model we did not observe any differences in the overall survival (OS), recurrence-free survival (RFS), and quality of life data between breast cancer patients with standard treatment and those who in addition to standard treatment received ML-I treatment. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  5. G Protein Coupled Receptor Kinase 3 Regulates Breast Cancer Migration, Invasion, and Metastasis.

    Directory of Open Access Journals (Sweden)

    Matthew J Billard

    Full Text Available Triple negative breast cancer (TNBC is a heterogeneous disease that has a poor prognosis and limited treatment options. Chemokine receptor interactions are important modulators of breast cancer metastasis; however, it is now recognized that quantitative surface expression of one important chemokine receptor, CXCR4, may not directly correlate with metastasis and that its functional activity in breast cancer may better inform tumor pathogenicity. G protein coupled receptor kinase 3 (GRK3 is a negative regulator of CXCR4 activity, and we show that GRK expression correlates with tumorigenicity, molecular subtype, and metastatic potential in human tumor microarray analysis. Using established human breast cancer cell lines and an immunocompetent in vivo mouse model, we further demonstrate that alterations in GRK3 expression levels in tumor cells directly affect migration and invasion in vitro and the establishment of distant metastasis in vivo. The effects of GRK3 modulation appear to be specific to chemokine-mediated migration behaviors without influencing tumor cell proliferation or survival. These data demonstrate that GRK3 dysregulation may play an important part in TNBC metastasis.

  6. G Protein Coupled Receptor Kinase 3 Regulates Breast Cancer Migration, Invasion, and Metastasis

    Science.gov (United States)

    Billard, Matthew J.; Fitzhugh, David J.; Parker, Joel S.; Brozowski, Jaime M.; McGinnis, Marcus W.; Timoshchenko, Roman G.; Serafin, D. Stephen; Lininger, Ruth; Klauber-Demore, Nancy; Sahagian, Gary; Truong, Young K.; Sassano, Maria F.; Serody, Jonathan S.; Tarrant, Teresa K.

    2016-01-01

    Triple negative breast cancer (TNBC) is a heterogeneous disease that has a poor prognosis and limited treatment options. Chemokine receptor interactions are important modulators of breast cancer metastasis; however, it is now recognized that quantitative surface expression of one important chemokine receptor, CXCR4, may not directly correlate with metastasis and that its functional activity in breast cancer may better inform tumor pathogenicity. G protein coupled receptor kinase 3 (GRK3) is a negative regulator of CXCR4 activity, and we show that GRK expression correlates with tumorigenicity, molecular subtype, and metastatic potential in human tumor microarray analysis. Using established human breast cancer cell lines and an immunocompetent in vivo mouse model, we further demonstrate that alterations in GRK3 expression levels in tumor cells directly affect migration and invasion in vitro and the establishment of distant metastasis in vivo. The effects of GRK3 modulation appear to be specific to chemokine-mediated migration behaviors without influencing tumor cell proliferation or survival. These data demonstrate that GRK3 dysregulation may play an important part in TNBC metastasis. PMID:27049755

  7. Association study of prostate cancer susceptibility variants with risks of invasive ovarian, breast, and colorectal cancer

    DEFF Research Database (Denmark)

    Song, H.; Koessler, T.; Ahmed, S.

    2008-01-01

    test of association was a comparison of genotype frequencies between cases and controls, and a test for trend stratified by study where appropriate. Genotype-specific odds ratios (OR) were estimated by logistic regression. SNP rs2660753 (chromosome 3p12) showed evidence of association with ovarian......Several prostate cancer susceptibility loci have recently been identified by genome-wide association studies. These loci are candidates for susceptibility to other epithelial cancers. The aim of this study was to test these tag single nucleotide polymorphisms (SNP) for association with invasive...... ovarian, colorectal, and breast cancer. Twelve prostate cancer-associated tag SNPs were genotyped in ovarian (2,087 cases/3,491 controls), colorectal (2,148 cases/2,265 controls) and breast (first set, 4,339 cases/4,552 controls; second set, 3,800 cases/3,995 controls) case-control studies. The primary...

  8. Heterogeneous Chromosomal Aberrations in Intraductal Breast Lesions Adjacent to Invasive Carcinoma

    Directory of Open Access Journals (Sweden)

    Michaela Aubele

    2000-01-01

    Full Text Available There is evidence that breast cancer is a heterogeneous disease phenotypically as well as molecular biologically. So far, heterogeneity on the molecular biological level has not been investigated in potential precursor lesions, such as ductal hyperplasia (DH and ductal carcinoma in situ (DCIS. In this study we applied comparative genomic hybridization (CGH to formalin‐fixed, paraffin‐embedded breast tissue with DH and DCIS, adjacent to invasive ductal carcinoma (IDC, to screen these potential precursor lesions for whole genomic chromosomal imbalances. Laser‐microdissection was used to select pure cell populations from the sections. Isolated DNA was amplified by degenerate oligonucleotide primed PCR (DOP‐PCR and further processed for CGH analysis.

  9. Value of shear-wave elastography in the diagnosis of symptomatic invasive lobular breast cancer

    International Nuclear Information System (INIS)

    Sim, Y.T.; Vinnicombe, S.; Whelehan, P.; Thomson, K.; Evans, A.

    2015-01-01

    Aim: To investigate the contribution of shear-wave elastography (SWE) in diagnosing invasive lobular breast cancer (ILC) in symptomatic patients. Materials and methods: A retrospective case-controlled study of 52 patients with ILC and 52 patients with invasive ductal cancer (IDC), matched for age and tumour size, was performed. Breast density and mammographic and greyscale ultrasound features were graded using Breast Imaging-Reporting and Data System (BI-RADS) classification by two radiologists, blinded to SWE and pathology findings. Forty-four benign lesions were also included. The sensitivity of SWE was assessed, using a cut-off value of 50 kPa for mean elasticity. Statistical significance was evaluated using Chi-square and Chi-square for trend tests. Results: Mean age for both ILC and IDC groups was 67 years. Mean size for ILC was 44 mm and IDC was 37 mm. The sensitivity for detection of ILC and IDC for mammography, greyscale ultrasound, and SWE were 79% versus 87%, 87% versus 98%, 94% versus 100%, respectively. SWE had significantly higher sensitivities than mammography for the detection of both ILC and IDC (p = 0.012 and p = 0.001, respectively). SWE was not significantly more sensitive than greyscale ultrasound for the detection of either tumour type. Four (8%) lobular cancers were benign/normal at both mammography and greyscale ultrasound, but suspicious on SWE. The incremental gain in sensitivity by using SWE in ILC was statistically significant compared to IDC (p = 0.01). Conclusion: SWE can diagnose lobular cancers that have benign/normal findings on conventional imaging as suspicious. - Highlights: • Sensitivity of shear-wave elastography (SWE) for detecting lobular cancers is 94%. • Sensitivity of SWE for detecting invasive ductal cancers is 100%. • SWE is more sensitive than mammography for detecting ductal and lobular cancers. • SWE can diagnose ILC as suspicious, which are benign/normal on conventional imaging

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

    Directory of Open Access Journals (Sweden)

    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

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

    Science.gov (United States)

    2017-11-15

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

  12. 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

  13. 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

  14. 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.

  15. 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.

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

    Directory of Open Access Journals (Sweden)

    de Souza Emanuel M

    2009-03-01

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

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

    International Nuclear Information System (INIS)

    Seniski, Gerusa G; Zanata, Silvio M; Costa, Fabrício F; Klassen, Giseli; Camargo, Anamaria A; Ierardi, Daniela F; Ramos, Edneia AS; Grochoski, Mariana; Ribeiro, Enilze SF; Cavalli, Iglenir J; Pedrosa, Fabio O; Souza, Emanuel M de

    2009-01-01

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

  18. Peritumoral apparent diffusion coefficients for prediction of lymphovascular invasion in clinically node-negative invasive breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Mori, Naoko; Mugikura, Shunji; Takasawa, Chiaki; Shimauchi, Akiko; Ota, Hideki; Takase, Kei; Takahashi, Shoki [Tohoku University Graduate School of Medicine, Department of Diagnostic Radiology, Sendai (Japan); Miyashita, Minoru; Ishida, Takanori [Tohoku University Graduate School of Medicine, Department of Surgical Oncology, Sendai (Japan); Kasajima, Atsuko [Tohoku University Graduate School of Medicine, Department of Pathology, Sendai (Japan); Kodama, Tetsuya [Tohoku University Graduate School of Medicine, Department of Biomedical Engineering, Sendai (Japan)

    2016-02-15

    To evaluate whether visual assessment of T2-weighted imaging (T2WI) or an apparent diffusion coefficient (ADC) could predict lymphovascular invasion (LVI) status in cases with clinically node-negative invasive breast cancer. One hundred and thirty-six patients with 136 lesions underwent MRI. Visual assessment of T2WI, tumour-ADC, peritumoral maximum-ADC and the peritumour-tumour ADC ratio (the ratio between them) were compared with LVI status of surgical specimens. No significant relationship was found between LVI and T2WI. Tumour-ADC was significantly lower in the LVI-positive (n = 77, 896 ± 148 x 10{sup -6} mm{sup 2}/s) than the LVI-negative group (n = 59, 1002 ± 163 x 10{sup -6} mm{sup 2}/s; p < 0.0001). Peritumoral maximum-ADC was significantly higher in the LVI-positive (1805 ± 355 x 10{sup -6} mm{sup 2}/s) than the LVI-negative group (1625 ± 346 x 10{sup -6} mm{sup 2}/s; p = 0.0003). Peritumour-tumour ADC ratio was significantly higher in the LVI-positive (2.05 ± 0.46) than the LVI-negative group (1.65 ± 0.40; p < 0.0001). Receiver operating characteristic curve analysis revealed that the area under the curve (AUC) of the peritumour-tumour ADC ratio was the highest (0.81). The most effective threshold for the peritumour-tumour ADC ratio was 1.84, and the sensitivity, specificity, positive predictive value and negative predictive value were 77 % (59/77), 76 % (45/59), 81 % (59/73) and 71 % (45/63), respectively. We suggest that the peritumour-tumour ADC ratio can assist in predicting LVI status on preoperative imaging. (orig.)

  19. Breast conserving treatment for breast cancer: dosimetric comparison of different non-invasive techniques for additional boost delivery

    International Nuclear Information System (INIS)

    Van Parijs, Hilde; Reynders, Truus; Heuninckx, Karina; Verellen, Dirk; Storme, Guy; De Ridder, Mark

    2014-01-01

    Today it is unclear which technique for delivery of an additional boost after whole breast radiotherapy for breast conserved patients should be state of the art. We present a dosimetric comparison of different non-invasive treatment techniques for additional boost delivery. For 10 different tumor bed localizations, 7 different non-invasive treatment plans were made. Dosimetric comparison of PTV-coverage and dose to organs at risk was performed. The Vero system achieved an excellent PTV-coverage and at the same time could minimize the dose to the organs at risk with an average near-maximum-dose (D2) to the heart of 0.9 Gy and the average volume of ipsilateral lung receiving 5 Gy (V5) of 1.5%. The TomoTherapy modalities delivered an average D2 to the heart of 0.9 Gy for the rotational and of 2.3 Gy for the static modality and an average V5 to the ipsilateral lung of 7.3% and 2.9% respectively. A rotational technique offers an adequate conformity at the cost of more low dose spread and a larger build-up area. In most cases a 2-field technique showed acceptable PTV-coverage, but a bad conformity. Electrons often delivered a worse PTV-coverage than photons, with the planning requirements achieved only in 2 patients and with an average D2 to the heart of 2.8 Gy and an average V5 to the ipsilateral lung of 5.8%. We present advices which can be used as guidelines for the selection of the best individualized treatment

  20. Phenotype-dependent effects of EpCAM expression on growth and invasion of human breast cancer cell lines

    Directory of Open Access Journals (Sweden)

    Martowicz Agnieszka

    2012-10-01

    Full Text Available Abstract Background The epithelial cell adhesion molecule (EpCAM has been shown to be overexpressed in breast cancer and stem cells and has emerged as an attractive target for immunotherapy of breast cancer patients. This study analyzes the effects of EpCAM on breast cancer cell lines with epithelial or mesenchymal phenotype. Methods For this purpose, shRNA-mediated knockdown of EpCAM gene expression was performed in EpCAMhigh breast cancer cell lines with epithelial phenotype (MCF-7, T47D and SkBR3. Moreover, EpCAMlow breast carcinoma cell lines with mesenchymal phenotype (MDA-MB-231, Hs578t and inducible overexpression of EpCAM were used to study effects on proliferation, migration and in vivo growth. Results In comparison to non-specific silencing controls (n/s-crtl knockdown of EpCAM (E#2 in EpCAMhigh cell lines resulted in reduced cell proliferation under serum-reduced culture conditions. Moreover, DNA synthesis under 3D culture conditions in collagen was significantly reduced. Xenografts of MCF-7 and T47D cells with knockdown of EpCAM formed smaller tumors that were less invasive. EpCAMlow cell lines with tetracycline-inducible overexpression of EpCAM showed no increased cell proliferation or migration under serum-reduced growth conditions. MDA-MB-231 xenografts with EpCAM overexpression showed reduced invasion into host tissue and more infiltrates of chicken granulocytes. Conclusions The role of EpCAM in breast cancer strongly depends on the epithelial or mesenchymal phenotype of tumor cells. Cancer cells with epithelial phenotype need EpCAM as a growth- and invasion-promoting factor, whereas tumor cells with a mesenchymal phenotype are independent of EpCAM in invasion processes and tumor progression. These findings might have clinical implications for EpCAM-based targeting strategies in patients with invasive breast cancer.

  1. Phenotype-dependent effects of EpCAM expression on growth and invasion of human breast cancer cell lines

    International Nuclear Information System (INIS)

    Martowicz, Agnieszka; Spizzo, Gilbert; Gastl, Guenther; Untergasser, Gerold

    2012-01-01

    The epithelial cell adhesion molecule (EpCAM) has been shown to be overexpressed in breast cancer and stem cells and has emerged as an attractive target for immunotherapy of breast cancer patients. This study analyzes the effects of EpCAM on breast cancer cell lines with epithelial or mesenchymal phenotype. For this purpose, shRNA-mediated knockdown of EpCAM gene expression was performed in EpCAM high breast cancer cell lines with epithelial phenotype (MCF-7, T47D and SkBR3). Moreover, EpCAM low breast carcinoma cell lines with mesenchymal phenotype (MDA-MB-231, Hs578t) and inducible overexpression of EpCAM were used to study effects on proliferation, migration and in vivo growth. In comparison to non-specific silencing controls (n/s-crtl) knockdown of EpCAM (E#2) in EpCAM high cell lines resulted in reduced cell proliferation under serum-reduced culture conditions. Moreover, DNA synthesis under 3D culture conditions in collagen was significantly reduced. Xenografts of MCF-7 and T47D cells with knockdown of EpCAM formed smaller tumors that were less invasive. EpCAM low cell lines with tetracycline-inducible overexpression of EpCAM showed no increased cell proliferation or migration under serum-reduced growth conditions. MDA-MB-231 xenografts with EpCAM overexpression showed reduced invasion into host tissue and more infiltrates of chicken granulocytes. The role of EpCAM in breast cancer strongly depends on the epithelial or mesenchymal phenotype of tumor cells. Cancer cells with epithelial phenotype need EpCAM as a growth- and invasion-promoting factor, whereas tumor cells with a mesenchymal phenotype are independent of EpCAM in invasion processes and tumor progression. These findings might have clinical implications for EpCAM-based targeting strategies in patients with invasive breast cancer

  2. 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.

  3. Macrophages promote matrix protrusive and invasive function of breast cancer cells via MIP-1β dependent upregulation of MYO3A gene in breast cancer cells

    Science.gov (United States)

    Baghel, Khemraj Singh; Tewari, Brij Nath; Shrivastava, Richa; Malik, Showkat Ahmad; Lone, Mehraj U-Din; Jain, Nem Kumar; Tripathi, Chakrapani; Kanchan, Ranjana Kumari; Dixit, Sameer; Singh, Kavita; Mitra, Kalyan; Negi, Mahendra Pal Singh; Srivastava, Mukesh; Misra, Sanjeev; Bhatt, Madan Lal Brahma; Bhadauria, Smrati

    2016-01-01

    ABSTRACT The potential of a tumor cell to metastasize profoundly depends on its microenvironment, or “niche” interactions with local components. Tumor-associated-macrophages (TAMs) are the most abundant subpopulation of tumor stroma and represent a key component of tumor microenvironment. The dynamic interaction of cancer cells with neighboring TAMs actively drive cancer progression and metastatic transformation through intercellular signaling networks that need better elucidation. Thus, current study was planned for discerning paracrine communication networks operational between TAMs, and breast cancer cells with special reference to cancer cell invasion and dissemination to distant sites. Here, we report role of MIP-1β in enhancing invasive potential of metastatic breast cancer MDA-MB-231 and MDA-MB-468 cells. In addition, the poorly metastatic MCF-7 cells were also rendered invasive by MIP-1β. The MIP-1β-driven cancer cell invasion was dependent on upregulated expression levels of MYO3A gene, which encodes an unconventional myosin super-family protein harboring a kinase domain. Ex ovo study employing Chick-embryo-model and in vivo Syngenic 4T1/BALB/c mice-model further corroborated aforementioned in vitro findings, thereby substantiating their physiological relevance. Concordantly, human breast cancer specimen exhibited significant association between mRNA expression levels of MIP-1β and MYO3A. Both, MIP-1β and MYO3A exhibited positive correlation with MMP9, an established molecular determinant of cancer cell invasion. Higher expression of these genes correlated with poor survival of breast cancer patients. Collectively, these results point toward so far undisclosed MIP-1β/MYO3A axis being operational during metastasis, wherein macrophage-derived MIP-1β potentiated cancer cell invasion and metastasis via up regulation of MYO3A gene within cancer cells. Our study exposes opportunities for devising potential anti-metastatic strategies for efficient

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

    Directory of Open Access Journals (Sweden)

    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. ADAMTS1-mediated targeting of TSP-1 by PPARδ suppresses migration and invasion of breast cancer cells.

    Science.gov (United States)

    Ham, Sun Ah; Yoo, Taesik; Lee, Won Jin; Hwang, Jung Seok; Hur, Jinwoo; Paek, Kyung Shin; Lim, Dae-Seog; Han, Sung Gu; Lee, Chi-Ho; Seo, Han Geuk

    2017-11-07

    Migration and invasion of cancer cells into surrounding tissue is a key stage of cancer metastasis. Here, we show that peroxisome proliferator-activated receptor (PPAR) δ regulates migration and invasion of human breast cancer cells via thrombospondin-1 (TSP-1) and its degrading protease, a disintegrin and metalloprotease domains with thrombospondin motifs 1 (ADAMTS1). Activation of PPARδ by GW501516, a specific ligand for PPARδ, led to marked inhibition in the cell migration and TSP-1 expression of breast cancer. These effects were suppressed by small interfering RNA-mediated knock-down of ADAMTS1, indicating that ADAMTS1 is involved in PPARδ-mediated inhibition of migration and TSP-1 expression in breast cancer cells. In addition, ligand-activated PPARδ upregulated expression of ADAMTS1 at the transcriptional level via binding of PPARδ to a direct repeat-1 site within the ADAMTS1 gene promoter. Furthermore, ligand-activated PPARδ suppressed invasion of breast cancer cells in an ADAMTS1-dependent manner. Taken together, these results demonstrate that PPARδ suppresses migration and invasion of breast cancer cells by downregulating TSP-1 in a process mediated by upregulation of ADAMTS1.

  6. Correlation between conductivity and prognostic factors in invasive breast cancer using magnetic resonance electric properties tomography (MREPT).

    Science.gov (United States)

    Kim, Soo-Yeon; Shin, Jaewook; Kim, Dong-Hyun; Kim, Min Jung; Kim, Eun-Kyung; Moon, Hee Jung; Yoon, Jung Hyun

    2016-07-01

    To investigate the correlation between conductivity and prognostic factors of invasive breast cancer using magnetic resonance electric properties tomography (MREPT). This retrospective study was approved by the Institutional Review Board, and verbal informed consent was obtained prior to breast MRI. This study included 65 women with surgically confirmed invasive breast cancers measuring 1 cm or larger on T2-weighted fast spin echo (FSE). Phase-based MREPT and the coil combination technique were used to reconstruct conductivity. Simple and multiple linear regression analysis were used to find an independent factor associated with conductivity. In total tumours, tumours with HER-2 overexpression showed lower conductivity than those without, and HER-2 overexpression was independently associated with conductivity. In 37 tumours 2 cm or larger, tumours with high mitosis or PR positivity showed higher conductivity than those without, and high mitosis and PR positivity were independently associated with conductivity. In 28 tumours 1-2 cm in size, there were no differences in conductivity according to the prognostic factors. Conductivity values measured using MREPT are associated with the HER-2 overexpression status, and may provide information about mitosis and the PR status of invasive breast cancers 2 cm or larger. • In all tumours, HER-2 overexpression was independently associated with conductivity. • In tumours ≥ 2 cm, high mitosis and PR positivity were associated with conductivity. • Conductivity is associated with the HER-2 overexpression status of invasive breast cancers.

  7. Invasive lobular breast cancer: the prognostic impact of histopathological grade, E-cadherin and molecular subtypes.

    Science.gov (United States)

    Engstrøm, Monica J; Opdahl, Signe; Vatten, Lars J; Haugen, Olav A; Bofin, Anna M

    2015-02-01

    The aim of this study was to compare breast cancer specific survival (BCSS) for invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) and, further, to evaluate critically the prognostic value of histopathological grading of ILC and examine E-cadherin as a prognostic marker in ILC. The study comprised 116 lobular and 611 ductal breast carcinomas occurring between 1961 and 2008. All cases had been classified previously according to histopathological type and grade, stained for oestrogen receptor (ER), progesterone receptor (PR), antigen Ki67 (Ki67), epithelial growth factor receptor (EGFR), cytokeratin 5 (CK5) and human epidermal growth factor receptor 2 (HER2) and classified into molecular subtypes. For the present study, immunohistochemical staining for E-cadherin was performed. The Kaplan-Meier method and Cox proportional hazards models were used in the analyses. Grade 2 tumours comprised 85.3% of the lobular tumours and 51.9% of the ductal tumours. BCSS in ILC grade 2 was comparable to that of IDC grade 3. E-cadherin-negative ILC had a poorer prognosis compared to E-cadherin positive ILC and to IDC regardless of E-cadherin status. The implication of histopathological grading may differ in ILC compared to IDC. E-cadherin may be useful in prognostication in ILC and thereby influence the determination of treatment strategies for this group of women. © 2014 The Authors. Histopathology published by John Wiley & Sons Ltd.

  8. ERBB2 mutations associated with solid variant of high-grade invasive lobular breast carcinomas.

    Science.gov (United States)

    Deniziaut, Gabrielle; Tille, Jean Christophe; Bidard, François-Clément; Vacher, Sophie; Schnitzler, Anne; Chemlali, Walid; Trémoulet, Laurence; Fuhrmann, Laetitia; Cottu, Paul; Rouzier, Roman; Bièche, Ivan; Vincent-Salomon, Anne

    2016-11-08

    ERBB2 and ERBB3 somatic gain-of-function mutations, which may be targeted by anti-ERBB2 therapies, were reported by high-throughput sequencing studies in 1% and 2% of invasive breast cancers respectively. Our study aims to determine ERBB2 and ERBB3 mutations frequencies in grade 3 and/or ERBB2-positive invasive lobular breast carcinomas (ILC). All the 529 ILC surgically-excised registered at Institut Curie in the years 2005 to 2008 were reviewed. Thirty-nine grade 3 ERBB2-negative ILC and 16 ERBB2-positive ILC were retrieved and subjected to Sanger sequencing of the ERBB2 and ERBB3 activation mutation hotspots (ERBB2: exons 8, 17, 19, 20, 21; ERBB3: exons 3, 6, 7, 8). Among the 39 grade 3 ERBB2-negative ILC, six tumors were found to have at least one detectable ERBB2 activating mutation (incidence rate: 15%, 95%CI [4%-27%]). No ERBB2 mutation was found among the 16 ERBB2-positive ILC. No ERBB3 mutation was found in any of the 55 ILC. ERBB2 mutations were statistically associated with solid ILC features (p=0.01). Survival analyses showed no significant prognostic impact of ERBB2 mutations. Our study demonstrates that high grade ERBB2-negative ILC display a high frequency of ERBB2 mutations, and should be subjected to systematic genetic screening.

  9. 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.

  10. Breast MRI in Invasive Lobular Carcinoma: A Useful Investigation in Surgical Planning?

    Science.gov (United States)

    Parvaiz, Muhammad Asad; Yang, Peiming; Razia, Eisha; Mascarenhas, Margaret; Deacon, Caroline; Matey, Pilar; Isgar, Brian; Sircar, Tapan

    2016-01-01

    Magnetic resonance imaging (MRI) is highly sensitive in detecting invasive lobular carcinoma (ILC) of the breast. In our institution, patients who are deemed to be suitable for breast conserving surgery (BCS) with unifocal small ILC on standard imaging are offered breast MRI to exclude multifocal and larger ILC. Our study investigates the usefulness of breast MRI in ILC. A prospective cohort study over a 58-month period, including all consecutive patients with ILC having breast MRI. Primary objective was to find out the proportion of ILC patients where preoperative MRI caused a change in the surgical treatment. Secondary objectives included finding mastectomy rate (initial & final), re-operation rate, cancer size correlation with different imaging modalities and final histopathology, loco-regional recurrence and disease-free survival. A total of 334 bilateral breast MRI were performed including 72 (21.5%) MRI for ILC patients. All these MRI were carried out within 2 week of patients given the diagnosis (median 5.5 days). Age range was 24-83 (median 56.5) years. Nineteen of 72 ILC patients (26.4%) had a change in their planned operation from BCS to a different operation owing to MRI findings (seven patients with multifocal cancers, 10 with significantly larger size of the cancer and two with contralateral malignancy). Initial mastectomy rate was 31.9%, final mastectomy rate was 36.1% and re-operation rate in BCS group was 18.3%. MRI correlated better with ILC histopathology cancer size than mammogram and ultrasound scans. There was no statistically significant difference (p = 0.999) between the cancer size on histology (median 23 mm) and MRI (median 25 mm). However, mammogram (median 17 mm) and ultrasound (median 14.5 mm) scans showed cancer sizes significantly different to final histology cancer size (p = 0.0008 and p = 0.0021 respectively). Over a 44 months median follow-up (range 27-85), 95.8% disease-free survival and 98.6% overall survival have been observed

  11. Mammographic findings predicting an extensive intraductal component in early stage invasive breast cancer : analysis on microcalcification

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jeong Ah; Kim, Mi Hye; Lee, Mi Kyung; Oh, Ki Keun [College of Medicine, Yonsei University, Seoul (Korea, Republic of); Kim, Eun Kyung [Pundang CHA General Hospital, College of Medicine, Pochon CHA University, Seoul (Korea, Republic of)

    2000-05-01

    To analyze the mammographic findings of extensive intraductal component (EIC)-positive early invasive breast carcinoma and to determine the mammographic features which predict an EIC positivity in an invasive carcinoma. The mammographic and pathologic findings in 71 patients aged 34-79 (mean 50) years in whom stage I or II invasive breast carcinoma had been diagnosed were retrospectively analysed. The mammographic findings were assigned to one of three groups: mass, mass with microcalcification, or microcalcification only. The shape and distribution of a calcification were classified according to the BI-RADS lexicon, and its extent was classified as either more or less than 3 cm. To detect the presence or absence of EIC and the type of ductal carcinoma in situ (DCIS), the findings were re-examined by means of slide mappings. Twenty-eight of 71 patients (39%) showed ECI positivity. The mammographic findings of EIC-positive invasive cancer (n=3D28) were mass with microcalcification (n=3D14), microcalcification only (n=3D7) and mass only (n=3D7). The mammographic finding which predicted EIC positivity was mass with microcalcification (PPV:0.67, NPV:0.33, p=3D0.02). A mammographic of mass only (n=3D39) showed a significantly high negative predictive value for EIC positivity. (PPV 0.18, NPV 0.82, P less than 0.01). A comparison of cases with or without calcification showed that those with microcalcifications (n=3D32) showed a significantly high PPV of 0.66 (NPV:0.34, p less than 0.01) while those without calcification (n=3D39) showed a significantly high NPV of 0.82 (PPV:0.18, p less than 0.01). There were no significant differences in positive predictive values for EIC between the shape, distribution and extent of calcifications. Whenever microcalcification with or without mass is seen on mammographs obtained during early breast cancer, we can predict EIC-positivity, regardless of shape or distribution according to the BI-RADS lexicon. (author)

  12. Intratumoral metabolic heterogeneity predicts invasive components in breast ductal carcinoma in situ

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Hai-Jeon [Ewha Womans University School of Medicine, Department of Nuclear Medicine, Yangchun-Ku, Seoul (Korea, Republic of); Kim, Yemi [Ewha Womans University, Clinical Research Institute, Seoul (Korea, Republic of); Kim, Bom Sahn [Ewha Womans University School of Medicine, Department of Nuclear Medicine, Yangchun-Ku, Seoul (Korea, Republic of); Ewha Womans University, Clinical Research Institute, Seoul (Korea, Republic of)

    2015-12-15

    This study investigated whether texture-based imaging parameters could identify invasive components of ductal carcinoma in situ (DCIS). We enrolled 65 biopsy-confirmed DCIS patients (62 unilateral, 3 bilateral) who underwent {sup 18}F-FDG PET, diffusion-weighted imaging (DWI), or breast-specific gamma imaging (BSGI). We measured SUV{sub max} and intratumoral metabolic heterogeneity by the area under the curve (AUC) of cumulative SUV histograms (CSH) on PET, tumour-to-normal ratio (TNR) and coefficient of variation (COV) as an index of heterogeneity on BSGI, minimum ADC (ADC{sub min}) and ADC difference (ADC{sub diff}) as an index of heterogeneity on DWI. After surgery, final pathology was categorized as pure-DCIS (DCIS-P), DCIS with microinvasion (DCIS-MI), or invasive ductal carcinoma (IDC). Clinicopathologic features of DCIS were correlated with final classification. Final pathology confirmed 44 DCIS-P, 14 DCIS-MI, and 10 IDC. The invasive component of DCIS was significantly correlated with higher SUV{sub max} (p = 0.017) and lower AUC-CSH (p < 0.001) on PET, higher TNR (p = 0.008) and COV (p = 0.035) on BSGI, lower ADC{sub min} (p = 0.016) and higher ADC{sub diff} (p = 0.009) on DWI, and larger pathologic size (p = 0.018). On multiple regression analysis, AUC-CSH was the only significant predictor of invasive components (p = 0.044). The intratumoral metabolic heterogeneity of {sup 18}F-FDG PET was the most important predictor of invasive components of DCIS. (orig.)

  13. Design and pharmacophore modeling of biaryl methyl eugenol analogs as breast cancer invasion inhibitors.

    Science.gov (United States)

    Abdel Bar, Fatma M; Khanfar, Mohammad A; Elnagar, Ahmed Y; Badria, Farid A; Zaghloul, Ahmed M; Ahmad, Kadria F; Sylvester, Paul W; El Sayed, Khalid A

    2010-01-15

    Cell invasion and migration are required for the parent solid tumor cells to metastasize to distant organs. Microtubules form a polarized network, enabling organelle and protein movement throughout the cell. Cytoskeletal elements coordinately regulate cell's motility, adhesion, migration, exocytosis, endocytosis, and division. Thus, microtubule disruption can be a useful target to control cancer cell invasion and metastasis. The phenolic ether methyl eugenol (1), the major component of the essential oil of the leaves of Melaleuca ericifolia Sm. (Myrtaceae), was used as a starting scaffold to design eleven new and three known anti-tubulin agents 2-15 using carbon-carbon coupling reactions. A computer-assisted approach was used to design these new biaryl derivatives using colchicine-binding site of tubulin as the molecular target and colchicine as an active ligand. Several derivatives showed potent inhibitory activity against MDA-MB-231 cell migration at the 1-4microM dose range. The Z isomers, 4 and 15 were more active as invasion inhibitors compared to their structurally related E isomers, 2 and 14. The cytotoxic activities of compounds 2-15 against two breast cancer cell lines MDA-MB-231 and MCF-7 were evaluated. Anti-invasive activity of the semisynthetic derivatives is not due to a direct cytotoxic effect on MDA-MB-231. Analogs 2-15 may promote their anti-invasive activity through the induction of changes in cell morphology. A pharmacophore model was generated involving seven essential features for activity, which was consistent with a previously generated colchicine site inhibitors model. Copyright 2009 Elsevier Ltd. All rights reserved.

  14. Intratumoral metabolic heterogeneity predicts invasive components in breast ductal carcinoma in situ

    International Nuclear Information System (INIS)

    Yoon, Hai-Jeon; Kim, Yemi; Kim, Bom Sahn

    2015-01-01

    This study investigated whether texture-based imaging parameters could identify invasive components of ductal carcinoma in situ (DCIS). We enrolled 65 biopsy-confirmed DCIS patients (62 unilateral, 3 bilateral) who underwent 18 F-FDG PET, diffusion-weighted imaging (DWI), or breast-specific gamma imaging (BSGI). We measured SUV max and intratumoral metabolic heterogeneity by the area under the curve (AUC) of cumulative SUV histograms (CSH) on PET, tumour-to-normal ratio (TNR) and coefficient of variation (COV) as an index of heterogeneity on BSGI, minimum ADC (ADC min ) and ADC difference (ADC diff ) as an index of heterogeneity on DWI. After surgery, final pathology was categorized as pure-DCIS (DCIS-P), DCIS with microinvasion (DCIS-MI), or invasive ductal carcinoma (IDC). Clinicopathologic features of DCIS were correlated with final classification. Final pathology confirmed 44 DCIS-P, 14 DCIS-MI, and 10 IDC. The invasive component of DCIS was significantly correlated with higher SUV max (p = 0.017) and lower AUC-CSH (p < 0.001) on PET, higher TNR (p = 0.008) and COV (p = 0.035) on BSGI, lower ADC min (p = 0.016) and higher ADC diff (p = 0.009) on DWI, and larger pathologic size (p = 0.018). On multiple regression analysis, AUC-CSH was the only significant predictor of invasive components (p = 0.044). The intratumoral metabolic heterogeneity of 18 F-FDG PET was the most important predictor of invasive components of DCIS. (orig.)

  15. 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

  16. New Roles of Osteocytes in Proliferation, Migration and Invasion of Breast and Prostate Cancer Cells.

    Science.gov (United States)

    Cui, Yu-Xin; Evans, Bronwen A J; Jiang, Wen G

    2016-03-01

    Most cases of prostate and breast cancer metastasis occur to the bone, and are responsible for the majority of cancer-related deaths. Osteocytes constitute over 90% of adult bone cells. They orchestrate bone remodelling through determining osteoclast activity and affecting osteoblasts. The osteocyte lacuno-canalicular network is also intimately associated with the blood vessel network in the bone matrix. However, the roles of osteocytes in cancer cell invasion and metastasis remain unknown. In this study, we investigated the effects of early osteocytes on the behaviour of breast and prostate cancer cells. The proliferation of cultured cells was assessed using the AlamarBlue assay. The electric cell-substrate impedance sensing (ECIS) system was used to measure spreading, attachment and migratory behaviour of cancer cells in response to conditioned medium (CM) from mouse osteocytes. Other cell assays, including in vitro wound healing and transwell migration/invasion assays, were also applied to evaluate the effect of osteocytes on cancer cells. We found that CM from osteocytes from both monolayer and three-dimensional (3D) cultures, stimulated proliferation of DU145 and PC3 prostate cancer cells but not LNCaP cells compared to control medium. Osteocyte CM also stimulated proliferation of MDA-MB-231 and MCF-7 breast cancer cells. However, osteocyte CM promoted the migration and adhesion of PC3 and DU145 in prostate cancer cells but had the reverse effect on PZHPV7, a normal prostate epithelial cell line. In the breast cancer cells studied, osteocyte CM inhibited post-wound migration of MCF-7 and ZR-75.1 cells but not MDA-MB-231 cells. Moreover, osteocyte CM stimulated transwell chemotactic migration of MDA-MB-231 cells but not of MCF-7 and ZR-75.1 cells. Osteocytes play diverse roles in the proliferative and migratory potential of breast and prostate cancer cells that may be associated with cancer-specific bone metastasis and requires further investigation. Copyright

  17. Treatment choices for patients with invasive lobular breast cancer: a doctor survey.

    Science.gov (United States)

    Jacobs, Carmel; Ibrahim, Mohamed F K; Clemons, Mark; Hutton, Brian; Simos, Demetrios; Caudrelier, Jean-Michel; Graham, Ian D; Smith, Stephanie; Addison, Christina; Arnaout, Angel

    2015-08-01

    Invasive lobular breast cancer (ILC) has distinct features that present challenges for management. We surveyed doctors regarding management approaches, opinions on quality of evidence supporting their practice, and future research needs. An online questionnaire was developed and circulated to breast cancer surgical, radiation and medical oncologists. The questionnaire was completed by 88/428 doctors (20.6%); 22/56 (39.3%) surgeons, 21/64 (32.8%) radiation oncologists and 45/308 (14.6%) medical oncologists. The majority (65%) of surgeons were comfortable treating ILC patients using the same surgical management as patients with invasive ductal cancers (IDC). Furthermore, 25% would perform a similar surgery but would obtain larger gross margins. There was equipoise for radiation oncologists regarding whether or not ILC was an independent risk factor for local-regional recurrence after either breast-conserving surgery or mastectomy. Of those radiation oncologists who believe ILC is an independent risk factor for recurrence after mastectomy, 44.4% would offer radiation in the absence of usual indications. Medical oncologists approached systemic therapy for ILC patients similarly to those with comparable IDCs. Areas identified as most controversial and requiring future research were preoperative magnetic resonance imaging, radiotherapy post-mastectomy and the responsiveness of ILC to adjuvant chemotherapy compared with endocrine therapy. There is a variation in doctors' beliefs, management and opinions regarding the quality of evidence for the management of ILC. Clinical trials specifically assessing the management of ILC are required to guide clinical practice. © 2015 John Wiley & Sons, Ltd.

  18. Value of shear-wave elastography in the diagnosis of symptomatic invasive lobular breast cancer.

    Science.gov (United States)

    Sim, Y T; Vinnicombe, S; Whelehan, P; Thomson, K; Evans, A

    2015-06-01

    To investigate the contribution of shear-wave elastography (SWE) in diagnosing invasive lobular breast cancer (ILC) in symptomatic patients. A retrospective case-controlled study of 52 patients with ILC and 52 patients with invasive ductal cancer (IDC), matched for age and tumour size, was performed. Breast density and mammographic and greyscale ultrasound features were graded using Breast Imaging-Reporting and Data System (BI-RADS) classification by two radiologists, blinded to SWE and pathology findings. Forty-four benign lesions were also included. The sensitivity of SWE was assessed, using a cut-off value of 50 kPa for mean elasticity. Statistical significance was evaluated using Chi-square and Chi-square for trend tests. Mean age for both ILC and IDC groups was 67 years. Mean size for ILC was 44 mm and IDC was 37 mm. The sensitivity for detection of ILC and IDC for mammography, greyscale ultrasound, and SWE were 79% versus 87%, 87% versus 98%, 94% versus 100%, respectively. SWE had significantly higher sensitivities than mammography for the detection of both ILC and IDC (p = 0.012 and p = 0.001, respectively). SWE was not significantly more sensitive than greyscale ultrasound for the detection of either tumour type. Four (8%) lobular cancers were benign/normal at both mammography and greyscale ultrasound, but suspicious on SWE. The incremental gain in sensitivity by using SWE in ILC was statistically significant compared to IDC (p = 0.01). SWE can diagnose lobular cancers that have benign/normal findings on conventional imaging as suspicious. Copyright © 2015 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Ellen Ackerstaff

    2007-03-01

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

  20. 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

    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......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...

  1. Effect of aluminium on migratory and invasive properties of MCF-7 human breast cancer cells in culture.

    Science.gov (United States)

    Darbre, Philippa D; Bakir, Ayse; Iskakova, Elzira

    2013-11-01

    Aluminium (Al) has been measured in human breast tissue, nipple aspirate fluid and breast cyst fluid, and recent studies have shown that at tissue concentrations, aluminium can induce DNA damage and suspension growth in human breast epithelial cells. This paper demonstrates for the first time that exposure to aluminium can also increase migratory and invasive properties of MCF-7 human breast cancer cells. Long-term (32 weeks) but not short-term (1 week) exposure of MCF-7 cells to 10(-4) M aluminium chloride or 10(-4) M aluminium chlorohydrate increased motility of the cells as measured by live cell imaging (cumulative length moved by individual cells), by a wound healing assay and by migration in real time through 8 μm pores of a membrane using xCELLigence technology. Long-term exposure (37 weeks) to 10(-4) M aluminium chloride or 10(-4) M aluminium chlorohydrate also increased the ability of MCF-7 cells to invade through a matrigel layer as measured in real time using the xCELLigence system. Although molecular mechanisms remain to be characterized, the ability of aluminium salts to increase migratory and invasive properties of MCF-7 cells suggests that the presence of aluminium in the human breast could influence metastatic processes. This is important because mortality from breast cancer arises mainly from tumour spread rather than from the presence of a primary tumour in the breast. © 2013.

  2. The impact of lobular carcinoma in situ in association with invasive breast cancer on the rate of local recurrence in patients with early-stage breast cancer treated with breast-conserving therapy

    International Nuclear Information System (INIS)

    Jolly, Shruti; Kestin, Larry L.; Goldstein, Neal S.; Vicini, Frank A.

    2006-01-01

    Purpose: The significance of lobular carcinoma in situ (LCIS) associated with invasive breast cancer in patients undergoing breast-conserving therapy (BCT) remains controversial. We examined the impact of the presence and extent of LCIS associated with invasive breast cancer on clinical outcome in BCT patients. Methods and Materials: From 1980 to 1996, 607 cases of invasive breast cancer were treated with BCT. All slides were reviewed by a single pathologist. Positive margin was defined as presence of invasive carcinoma/ductal carcinoma in situ at the inked margin. Multiple clinical, pathologic, and treatment-related variables were analyzed for their association with ipsilateral breast tumor recurrence (IBTR) and true recurrence/marginal miss (TR/MM). Median follow-up was 8.7 years. Results: Fifty-six patients (9%) had LCIS in association with invasive cancer. On univariate analysis, positive final margin, positive/no reexcision, smaller maximum specimen dimension, and the presence of LCIS predicted for IBTR. The 10-year IBTR rate was 14% for cases with LCIS vs. 7% without LCIS (p = 0.04). On multivariate analysis, positive margin (p < 0.01), positive/no reexcision (p = 0.04), and presence of LCIS (p = 0.02) remained independently associated with IBTR; positive margin (p < 0.01) and LCIS (p = 0.04) were also associated with TR/MM failure. When examining only cases with negative final margins, the presence of LCIS remained associated with higher IBTR and TR/MM rates (p < 0.01). Conclusion: The presence of LCIS was independently associated with higher rate of IBTR and TR/MM after BCT for invasive breast cancer. LCIS may have significant premalignant potential and progress to an invasive IBTR at the site of index lesion. The adequacy of excision of LCIS associated with invasive carcinoma should be considered in patients undergoing BCT

  3. Epstein-Barr virus infection and breast invasive ductal carcinoma in Egyptian women: A single center experience.

    Science.gov (United States)

    El-Naby, Noha Ed Hassab; Hassan Mohamed, Hameda; Mohamed Goda, Asmaa; El Sayed Mohamed, Ahmed

    2017-06-01

    A controversy of the role of Epstein-Barr virus (EBV) infection in breast carcinomas has been reported in the literature. We carried on this research to explore possible association between EBV infection and breast invasive ductal carcinoma (IDC) in Egyptian women attending our center. This study carried out at Sohag university hospital on 84 paraffin embedded samples of breast tissue, of them 42 breast IDC as the case group and 42 breast fibroadenomas as the control group. Nested PCRand immunohistochemistry (IHC) done separately for all samples to identify the Epstein-Barr nuclear antigen-1 (EBNA-1) gene and EBV latent membrane protein-1 (LMP-1) respectively, in breast cancer cells and controls. Specimen considered positive when both (EBNA-1) gene and LMP-1 were detected using PCR and IHC separately for the same sample, this was achieved by 10/42 (23.81%) of breast IDC (case group) and 6/42 (14.29%) of breast fibro-adenomas (control group) (P-value=0.4). Nodal involvement was the only parameter that demonstrated a significant statistical relationship with EBV presence in cancerous tissue with p-value=0.003. Our research could not find a significant statistical association between EBV infection and breast IDC in Egyptian women attending our center, but, there might be an association between the existence of EBV and tumor aggressiveness. Copyright © 2017 National Cancer Institute, Cairo University. Production and hosting by Elsevier B.V. All rights reserved.

  4. Extra-nuclear signaling of progesterone receptor to breast cancer cell movement and invasion through the actin cytoskeleton.

    Directory of Open Access Journals (Sweden)

    Xiao-Dong Fu

    2008-07-01

    Full Text Available Progesterone plays a role in breast cancer development and progression but the effects on breast cancer cell movement or invasion have not been fully explored. In this study, we investigate the actions of natural progesterone and of the synthetic progestin medroxyprogesterone acetate (MPA on actin cytoskeleton remodeling and on breast cancer cell movement and invasion. In particular, we characterize the nongenomic signaling cascades implicated in these actions. T47-D breast cancer cells display enhanced horizontal migration and invasion of three-dimensional matrices in the presence of both progestins. Exposure to the hormones triggers a rapid remodeling of the actin cytoskeleton and the formation of membrane ruffles required for cell movement, which are dependent on the rapid phosphorylation of the actin-regulatory protein moesin. The extra-cellular small GTPase RhoA/Rho-associated kinase (ROCK-2 cascade plays central role in progesterone- and MPA-induced moesin activation, cell migration and invasion. In the presence of progesterone, progesterone receptor A (PRA interacts with the G protein G alpha(13, while MPA drives PR to interact with tyrosine kinase c-Src and to activate phosphatidylinositol-3 kinase, leading to the activation of RhoA/ROCK-2. In conclusion, our findings manifest that progesterone and MPA promote breast cancer cell movement via rapid actin cytoskeleton remodeling, which are mediated by moesin activation. These events are triggered by RhoA/ROCK-2 cascade through partially differing pathways by the two compounds. These results provide original mechanistic explanations for the effects of progestins on breast cancer progression and highlight potential targets to treat endocrine-sensitive breast cancers.

  5. Prolactin Signaling Stimulates Invasion via Na(+)/H(+) Exchanger NHE1 in T47D Human Breast Cancer Cells.

    Science.gov (United States)

    Pedraz-Cuesta, Elena; Fredsted, Jacob; Jensen, Helene H; Bornebusch, Annika; Nejsum, Lene N; Kragelund, Birthe B; Pedersen, Stine F

    2016-07-01

    Prolactin (PRL) and its receptor (PRLR) are implicated in breast cancer invasiveness, although their exact roles remain controversial. The Na(+)/H(+) exchanger (NHE1) plays essential roles in cancer cell motility and invasiveness, but the PRLR and NHE1 have not previously been linked. Here we show that in T47D human breast cancer cells, which express high levels of PRLR and NHE1, exposure to PRL led to the activation of Janus kinase-2 (JAK2)/signal transducer and activator of transcription-5 (STAT5), Akt, and ERK1/2 signaling and the rapid formation of peripheral membrane ruffles, known to be associated with cell motility. NHE1 was present in small ruffles prior to PRL treatment and was further recruited to the larger, more dynamic ruffles induced by PRL exposure. In PRL-induced ruffles, NHE1 colocalized with activated Akt, ERK1/2, and the ERK effector p90Ribosomal S kinase (p90RSK), known regulators of NHE1 activity. Stimulation of T47D cells with PRL augmented p90RSK activation, Ser703-phosphorylation of NHE1, NHE1-dependent intracellular pH recovery, pericellular acidification, and NHE1-dependent invasiveness. NHE1 activity and localization to ruffles were attenuated by the inhibition of Akt and/or ERK1/2. In contrast, noncancerous MCF10A breast epithelial cells expressed NHE1 and PRLR at lower levels than T47D cells, and their stimulation with PRL induced neither NHE1 activation nor NHE1-dependent invasiveness. In conclusion, we show for the first time that PRLR activation stimulates breast cancer cell invasiveness via the activation of NHE1. We propose that PRL-induced NHE1 activation and the resulting NHE1-dependent invasiveness may contribute to the metastatic behavior of human breast cancer cells.

  6. Prolactin Signaling Stimulates Invasion via Na+/H+ Exchanger NHE1 in T47D Human Breast Cancer Cells

    Science.gov (United States)

    Pedraz-Cuesta, Elena; Fredsted, Jacob; Jensen, Helene H.; Bornebusch, Annika; Nejsum, Lene N.; Kragelund, Birthe B.

    2016-01-01

    Prolactin (PRL) and its receptor (PRLR) are implicated in breast cancer invasiveness, although their exact roles remain controversial. The Na+/H+ exchanger (NHE1) plays essential roles in cancer cell motility and invasiveness, but the PRLR and NHE1 have not previously been linked. Here we show that in T47D human breast cancer cells, which express high levels of PRLR and NHE1, exposure to PRL led to the activation of Janus kinase-2 (JAK2)/signal transducer and activator of transcription-5 (STAT5), Akt, and ERK1/2 signaling and the rapid formation of peripheral membrane ruffles, known to be associated with cell motility. NHE1 was present in small ruffles prior to PRL treatment and was further recruited to the larger, more dynamic ruffles induced by PRL exposure. In PRL-induced ruffles, NHE1 colocalized with activated Akt, ERK1/2, and the ERK effector p90Ribosomal S kinase (p90RSK), known regulators of NHE1 activity. Stimulation of T47D cells with PRL augmented p90RSK activation, Ser703-phosphorylation of NHE1, NHE1-dependent intracellular pH recovery, pericellular acidification, and NHE1-dependent invasiveness. NHE1 activity and localization to ruffles were attenuated by the inhibition of Akt and/or ERK1/2. In contrast, noncancerous MCF10A breast epithelial cells expressed NHE1 and PRLR at lower levels than T47D cells, and their stimulation with PRL induced neither NHE1 activation nor NHE1-dependent invasiveness. In conclusion, we show for the first time that PRLR activation stimulates breast cancer cell invasiveness via the activation of NHE1. We propose that PRL-induced NHE1 activation and the resulting NHE1-dependent invasiveness may contribute to the metastatic behavior of human breast cancer cells. PMID:27176613

  7. The presence of proliferative breast disease with atypia does not influence outcome in invasive breast cancer treated with conservative surgery and radiation

    International Nuclear Information System (INIS)

    Fowble, B.; Hanlon, A.L.; Patchefsky, A.; Hoffman, J.P.; Sigurdson, E.R.; Goldstein, L.J.

    1997-01-01

    Purpose: Atypical hyperplasia (AH) (ductal or lobular) represents a marker for an increased risk for subsequent breast cancer in either breast, especially in premenopausal women and those with a positive family history. However, the impact of the presence of AH in association with an invasive breast cancer on ipsilateral breast recurrence rates or contralateral breast cancer in women treated with conservative surgery and radiation is unknown. For a number of clinicians the presence of marked proliferative changes with atypia at the time of diagnosis of an invasive cancer is an indication for mastectomy. In an attempt to address this issue, we compared the outcome of patients (pts) with proliferative disease with atypia to those in whom this pathologic feature was absent. Materials and Methods: From 1982-1994, 1537 women with stage I-II breast cancer underwent excisional biopsy, axillary dissection and radiation. 459 of these women had pathologic evaluation of the background adjacent benign breast tissue and represent the study population. The median followup was 6.3 yrs (range .1-14.5). The median age was 55 yrs (range 24 to 88). 23% had positive axillary nodes. 25% received adjuvant chemotherapy (CMF or CAF) with (9%) or without (16%) tamoxifen. 24% received tamoxifen alone. The study population was divided into 2 groups: 131 pts with atypical hyperplasia (ductal 99 pts, lobular 20 pts, and type not specified 12 pts) and 328 pts with no proliferative changes or proliferative changes without atypia. The comparability of the 2 groups was assessed for the following factors: clinical (race, age, menopausal status, method of detection of primary, primary tumor size, and family history), pathologic (histology, final resection margin, pathologic nodal status, presence or absence of LCIS, histologic subtype DCIS when present and estrogen and progesterone receptor status) and treatment related (re-excision and adjuvant chemotherapy and/or tamoxifen). Outcome was evaluated

  8. Increased Detection of Lymphatic Vessel Invasion by D2-40 (Podoplanin) in Early Breast Cancer: Possible Influence on Patient Selection for Accelerated Partial Breast Irradiation

    International Nuclear Information System (INIS)

    Debald, Manuel; Poelcher, Martin; Flucke, Uta; Walgenbach-Bruenagel, Gisela

    2010-01-01

    Purpose: Several international trials are currently investigating accelerated partial breast irradiation (APBI) for patients with early-stage breast cancer. According to existing guidelines, patients with lymphatic vessel invasion (LVI) do not qualify for APBI. D2-40 (podoplanin) significantly increases the frequency of LVI detection compared with conventional hematoxylin and eosin (HE) staining in early-stage breast cancer. Our purpose was to retrospectively assess the hypothetical change in management from APBI to whole breast radiotherapy with the application of D2-40. Patients and Methods: Immunostaining with D2-40 was performed on 254 invasive breast tumors of 247 patients. The following criteria were used to determine the eligibility for APBI: invasive ductal adenocarcinoma of ≤3 cm, negative axillary node status (N0), and unifocal disease. Of the 247 patients, 74 with available information concerning LVI, as detected by D2-40 immunostaining and routine HE staining, formed our study population. Results: Using D2-40, our results demonstrated a significantly greater detection rate (p = .031) of LVI compared with routine HE staining. LVI was correctly identified by D2-40 (D2-40-positive LVI) in 10 (13.5%) of 74 tumors. On routine HE staining, 4 tumors (5.4%) were classified as HE-positive LVI. Doublestaining of these specimens with D2-40 unmasked false-positive LVI status in 2 (50%) of the 4 tumors. According to the current recommendations for APBI, immunostaining with D2-40 would have changed the clinical management from APBI to whole breast radiotherapy in 8 (10.8%) of 74 patients and from whole breast radiotherapy to APBI in 2 patients (2.7%). Conclusion: These data support the implementation of D2-40 immunostaining in the routine workup to determine a patient's eligibility for APBI.

  9. Preoperative Magnetic Resonance Imaging in Patients With Stage I Invasive Ductal Breast Cancer: A Prospective Randomized Study.

    Science.gov (United States)

    Brück, N; Koskivuo, I; Boström, P; Saunavaara, J; Aaltonen, R; Parkkola, R

    2018-03-01

    Preoperative magnetic resonance imaging has become an important complementary imaging technique in patients with breast cancer, providing additional information for preoperative local staging. Magnetic resonance imaging is recommended selectively in lobular breast cancer and in patients with dense breast tissue in the case when mammography and ultrasound fail to fully evaluate the lesion, but the routine use of magnetic resonance imaging in all patients with invasive ductal carcinoma is controversial. The purpose of this randomized study was to investigate the diagnostic value of preoperative magnetic resonance imaging and its impact on short-term surgical outcome in newly diagnosed unifocal stage I invasive ductal carcinoma. A total of 100 patients were randomized to either receive preoperative breast magnetic resonance imaging or to be scheduled directly to operation without magnetic resonance imaging on a 1:1 basis. There were 50 patients in both study arms. In 14 patients (28%), breast magnetic resonance imaging detected an additional finding and seven of them were found to be malignant. Six additional cancer foci were found in the ipsilateral breast and one in the contralateral breast. Magnetic resonance imaging findings caused a change in planned surgical management in 10 patients (20%). Mastectomy was performed in six patients (12%) in the magnetic resonance imaging group and in two patients (4%) in the control group ( p = 0.140). The breast reoperation rate was 14% in the magnetic resonance imaging group and 24% in the control group ( p = 0.202). The mean interval between referral and first surgical procedure was 34 days in the magnetic resonance imaging group and 21 days in the control group ( p magnetic resonance imaging may be beneficial for some patients with early-stage invasive ductal carcinoma, but its routine use is not recommended without specific indications.

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

    Directory of Open Access Journals (Sweden)

    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.

  11. The role of annexin A1 in expression of matrix metalloproteinase-9 and invasion of breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Hyereen [Department of Medicine, Graduate School, University of Ulsan, Pungnap-2 dong, Songpa-gu, Seoul (Korea, Republic of); Ko, Jesang [School of Life Sciences and Biotechnology, Korea University, Seoul 136-701 (Korea, Republic of); Jang, Sung-Wuk, E-mail: swjang@amc.seoul.kr [Department of Medicine, Graduate School, University of Ulsan, Pungnap-2 dong, Songpa-gu, Seoul (Korea, Republic of)

    2012-06-22

    Highlights: Black-Right-Pointing-Pointer We evaluated the effect of ANXA1 on promoting migration and invasion in MDA-MB-231 cells. Black-Right-Pointing-Pointer ANXA1 siRNA inhibits invasion and migration. Black-Right-Pointing-Pointer ANXA1 regulates MMP-9 expression and activity. Black-Right-Pointing-Pointer ANX-1 siRNA inhibits the activation of NF-{kappa}B in MDA-MB-231 cells. -- Abstract: Matrix metalloproteinase-9 (MMP-9) plays an important role in the invasion and metastasis of cancer cells. However, the regulatory mechanism of MMP-9 expression and its biological effects on breast cancer development remain obscure. In the current study, we examined the potential role of annexin A1 (ANXA1) in regulating migration and invasion in breast cancer cell lines. Both ANXA1 mRNA and protein are expressed in the highly invasive, hormone-insensitive human breast cancer cell lines MDA-MB-231 and SKBr3, but not in the hormone-responsive cell lines MCF-7 and T47D. Downregulation of ANXA1 expression with specific small interfering RNAs (ANXA1 siRNA) in MDA-MB-231 cells resulted in decreased cancer cell migration and invasion. Ablation of ANXA1 expression decreases the expression of MMP-9 at both the mRNA and protein levels and also reduces the proteolytic activity of MMP-9 in MDA-MB-231 cells. Moreover, silencing ANXA1 also decreases the transcriptional activity of MMP-9 by the suppression of nuclear factor kappa-B (NF-{kappa}B) activity. Collectively, these results indicate that ANXA1 functions as a positive regulator of MMP-9 expression and invasion of breast cancer cells through specific activation of the NF-{kappa}B signaling pathway.

  12. Trends in incidence and tumour grade in screen-detected ductal carcinoma in situ and invasive breast cancer.

    Science.gov (United States)

    Luiten, Jacky D; Voogd, Adri C; Luiten, Ernest J T; Duijm, Lucien E M

    2017-11-01

    In a biennial screening mammography programme, we analysed the trends in incidence of screen-detected DCIS and invasive breast cancers in the era of screen-film mammography (SFM) screening, the period of the transition to full-field digital mammography (FFDM) screening and the period of FFDM screening. We also investigated a possible association between the incidence and grading of screen-detected DCIS and invasive breast cancer. In the southern part of the Netherlands, FFDM screening gradually replaced SFM screening between May 2009 and April 2010. We included a consecutive series of 484, 422 screens obtained between July 2005 and July 2015 and divided these screens into three groups; SFM-only cohort, transition cohort and FFDM-only cohort. A total of 3059 referred women were diagnosed with DCIS (n = 623) or invasive breast cancer (n = 2436). The majority of DCIS were high-grade (48.2%), whereas the majority of the invasive breast cancers were low-grade (45.4%) or intermediate-grade (41.6%). The cancer detection rate (CDR) per 1000 screened women showed the same distribution by grade in both groups. The transition to FFDM was characterised by an increased overall detection rate of invasive cancers. Screening mammography detects mostly high-grade DCIS and low- or intermediate-grade invasive cancers. The grade distribution as well as the CDR in the years after the introduction of FFDM remained stable compared to the era of SFM screening. By diagnosing and treating high-grade DCIS, which otherwise may develop into high-grade invasive carcinoma, our findings provide new evidence for the beneficial value of screening mammography programmes.

  13. Simultaneous loss of E-cadherin and catenins in invasive lobular breast cancer and lobular carcinoma in situ

    NARCIS (Netherlands)

    de Leeuw, W. J.; Berx, G.; Vos, C. B.; Peterse, J. L.; van de Vijver, M. J.; Litvinov, S.; van Roy, F.; Cornelisse, C. J.; Cleton-Jansen, A. M.

    1997-01-01

    Loss of expression of the intercellular adhesion molecule E-cadherin frequently occurs in invasive lobular breast carcinomas as a result of mutational inactivation. Expression patterns of E-cadherin and the molecules comprising the cytoplasmic complex of adherens junctions, alpha-, beta- and

  14. Overexpression of ErbB2 induces invasion of MCF10A human breast epithelial cells via MMP-9.

    Science.gov (United States)

    Kim, In-Young; Yong, Hae-Young; Kang, Keon Wook; Moon, Aree

    2009-03-18

    Metastasis is the principal cause of death from breast cancer. ErbB2 (HER-2/neu) has been identified as an important regulator of metastatic potential of breast cancer. The present study investigated the molecular mechanism underlying the role of ErbB2 in malignant phenotypic conversion of MCF10A human breast epithelial cells which originally have 'normal' cell character. Here we report that ErbB2 induces invasion and migration of MCF10A cells though up-regulation of matrix metalloproteinase (MMP)-9. We also observed a marked reduction of an epithelial cell marker, E-cadherin, and an induction of vimentin in ErbB2-MCF10A cells, suggesting that epithelial-mesenchymal transition may play a role in the ErbB2-induced invasion and migration of MCF10A cells. Overexpression of ErbB2 significantly activated p38 MAPK and Akt, while Raf-1/MEK/ERK pathway was not activated by ErbB2. Using pharmacological inhibitors, we further show that p38 MAPK and Akt signaling pathways are crucial for the ErbB2-induced MMP-9 up-regulation, invasion and migration of MCF10A cells. Given that ErbB2 is one of the most important oncogenes in human breast cancer and thus is an attractive therapeutic target, our findings may provide a molecular basis for the promoting role of ErbB2 in breast cancer progression.

  15. Stanniocalicin 2 suppresses breast cancer cell migration and invasion via the PKC/claudin-1-mediated signaling.

    Directory of Open Access Journals (Sweden)

    Jing Hou

    Full Text Available Stanniocalcin (STC, a glycoprotein hormone, is expressed in a wide variety of tissues to regulate Ca2+ and PO4- homeostasis. STC2, a member of STC family, has been reported to be associated with tumor development. In this study, we investigated whether the expression of STC2 is associated with migration and invasion of breast cancer cells. We found that breast cancer cell line 231 HM transfected with STC2 shRNA displayed high motility, fibroblast morphology, and enhanced cell migration and invasion. Introduction of STC2 in 231 cells reduced cell migration and invasion. In response to irradiation, silencing of STC2 in 231 HM cells reduced apoptosis, whereas overexpression of STC2 in 231 cells promoted apoptosis, compared with in control cells. Mechanistic study showed that STC2 negatively regulated PKC to control the expression of Claudin-1, which subsequently induced the expressions of EMT-related factors including ZEB1, ZO-1, Slug, Twist, and MMP9. Suppression of PKC activity by using a PKC inhibitor (Go 6983 restored the normal motility of STC2-silenced cells. Furthermore, in vivo animal assay showed that STC2 inhibited tumorigenesis and metastasis of breast cancer cells. Collectively, these results indicate that STC2 may inhibit EMT at least partially through the PKC/Claudin-1-mediated signaling in human breast cancer cells. Thus, STC2 may be exploited as a biomarker for metastasis and targeted therapy in human breast cancer.

  16. Invasive Pleomorphic Lobular Histology Is an Adverse Prognostic Factor on Survival in Patients with Breast Cancer.

    Science.gov (United States)

    Sahin, Suleyman; Karatas, Fatih; Erdem, Gokmen U; Hacioglu, Bekir; Altundag, Kadri

    2017-04-01

    Invasive pleomorphic lobular carcinoma (IPLC) is defined to be an uncommon and different subtype of classical invasive lobular carcinoma (ILC). This special variant is characterized by significant cytological atypia and pleomorphism which differs from the cytological uniformity of ILC. IPLC has been shown to have some poor prognostic factors such as axillary node metastasis and higher histological grade which may lead to poor clinical courses including a short relapse time, increased risk of recurrence and a decreased survival. The aim of this study is to investigate the clinicopathological characteristics and prognosis of IPLC in comparison with ILC and also to evaluate if IPLC is a different clinical entity compared to ILC. A total number of 4418 breast cancer patients treated between 1996 and 2015 in Hacettepe University Cancer Institute, were retrospectively analyzed. Among 4418 patients, 210 were diagnosed with ILC and 23 patients diagnosed with pure IPLC. In this present study, clinicopathological characteristics, disease free survival (DFS) and overall survival (OS) of patients with ILC and IPLC were compared. This study design is one of the rare face to face comparison of pure IPLC and ILC. Patients with IPLC had an increased rate of higher histologic grade, extracapsular extension, lymphovascular invasion and lower percentage of hormone positivity than those of patients with ILC. During the follow-up time, IPLC group experienced 4 cases (17.3%) of recurrence, 5 cases (21.7%) of death and 2 cases (8.7%) of progression in 3 metastatic patients compared to that of 27 cases (12.9%) of recurrence, 29 cases (13,8%) of death and 14 cases (6.7%) of progression in 19 metastatic patients in the ILC group. Patients with IPLC had a worse DFS and OS duration than patients with ILC (P = 0.02 for OS, P = 0.04 for DFS). In conclusion, IPLC is a different and a special breast cancer subtype. This study suggests that IPLC is a distinct clinical entity with an advanced stage

  17. Clinical Outcomes Using Accelerated Partial Breast Irradiation in Patients With Invasive Lobular Carcinoma

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    Shah, Chirag; Wilkinson, J. Ben; Shaitelman, Simona; Grills, Inga; Wallace, Michelle; Mitchell, Christina [Department of Radiation Oncology, Beaumont Cancer Institute, Oakland University William Beaumont School of Medicine, Royal Oak, MI (United States); Vicini, Frank, E-mail: fvicini@beaumont.edu [Department of Radiation Oncology, Beaumont Cancer Institute, Oakland University William Beaumont School of Medicine, Royal Oak, MI (United States)

    2011-11-15

    Purpose: We compared clinical outcomes of women diagnosed with either invasive lobular carcinoma (ILC) or invasive ductal carcinoma (IDC) treated with accelerated partial breast irradiation (APBI). Methods and Materials: A total of 16 patients with ILC received APBI as part of their breast-conservation therapy (BCT) and were compared with 410 patients with IDC that received APBI as part of their BCT. Clinical, pathologic, and treatment related variables were analyzed including age, tumor size, hormone receptor status, surgical margins, lymph node status, adjuvant hormonal therapy, adjuvant chemotherapy, and APBI modality. Clinical outcomes including local recurrence (LR), regional recurrence (RR), disease-free survival (DFS), cause-specific survival (CSS), and overall survival (OS) were analyzed. Results: Median follow-up was 3.8 years for the ILC patients and 6.0 years for the IDC patients. ILC patients were more likely to have positive margins (20.0% vs. 3.9%, p = 0.006), larger tumors (14.1 mm vs. 10.9 mm, p = 0.03) and less likely to be node positive (0% vs. 9.5%, p < 0.001) when compared with patients diagnosed with IDC. The 5-year rate of LR was 0% for the ILC cohort and 2.5% for the IDC cohort (p = 0.59). No differences were seen in the rates of RR (0% vs. 0.7%, p = 0.80), distant metastases (0% vs. 3.5%, p = 0.54), DFS (100% vs. 94%, p = 0.43), CSS (100% vs. 97%, p = 0.59), or OS (92% vs. 89%, p = 0.88) between the ILC and IDC patients, respectively. Additionally, when node-positive patients were excluded from the IDC cohort, no differences in the rates of LR (0% vs. 2.2%, p = 0.62), RR (0% vs. 0%), DFS (100% vs. 95%, p = 0.46), CSS (100% vs. 98%, p = 0.63), or OS (92% vs. 89%, p = 0.91) were noted between the ILC and IDC patients. Conclusion: Women with ILC had excellent clinical outcomes after APBI. No difference in local control was seen between patients with invasive lobular versus invasive ductal histology.

  18. Clinical Outcomes Using Accelerated Partial Breast Irradiation in Patients With Invasive Lobular Carcinoma

    International Nuclear Information System (INIS)

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

    2011-01-01

    Purpose: We compared clinical outcomes of women diagnosed with either invasive lobular carcinoma (ILC) or invasive ductal carcinoma (IDC) treated with accelerated partial breast irradiation (APBI). Methods and Materials: A total of 16 patients with ILC received APBI as part of their breast-conservation therapy (BCT) and were compared with 410 patients with IDC that received APBI as part of their BCT. Clinical, pathologic, and treatment related variables were analyzed including age, tumor size, hormone receptor status, surgical margins, lymph node status, adjuvant hormonal therapy, adjuvant chemotherapy, and APBI modality. Clinical outcomes including local recurrence (LR), regional recurrence (RR), disease-free survival (DFS), cause-specific survival (CSS), and overall survival (OS) were analyzed. Results: Median follow-up was 3.8 years for the ILC patients and 6.0 years for the IDC patients. ILC patients were more likely to have positive margins (20.0% vs. 3.9%, p = 0.006), larger tumors (14.1 mm vs. 10.9 mm, p = 0.03) and less likely to be node positive (0% vs. 9.5%, p < 0.001) when compared with patients diagnosed with IDC. The 5-year rate of LR was 0% for the ILC cohort and 2.5% for the IDC cohort (p = 0.59). No differences were seen in the rates of RR (0% vs. 0.7%, p = 0.80), distant metastases (0% vs. 3.5%, p = 0.54), DFS (100% vs. 94%, p = 0.43), CSS (100% vs. 97%, p = 0.59), or OS (92% vs. 89%, p = 0.88) between the ILC and IDC patients, respectively. Additionally, when node-positive patients were excluded from the IDC cohort, no differences in the rates of LR (0% vs. 2.2%, p = 0.62), RR (0% vs. 0%), DFS (100% vs. 95%, p = 0.46), CSS (100% vs. 98%, p = 0.63), or OS (92% vs. 89%, p = 0.91) were noted between the ILC and IDC patients. Conclusion: Women with ILC had excellent clinical outcomes after APBI. No difference in local control was seen between patients with invasive lobular versus invasive ductal histology.

  19. 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.

  20. Three-dimensional collagen represses cyclin E1 via β1 integrin in invasive breast cancer cells.

    Science.gov (United States)

    Wu, Yuehan; Guo, Xun; Brandt, Yekaterina; Hathaway, Helen J; Hartley, Rebecca S

    2011-06-01

    The behavior of breast epithelial cells is influenced by their microenvironment which includes stromal cells and extracellular matrix (ECM). During cancer progression, the tissue microenvironment fails to control proliferation and differentiation, resulting in uncontrolled growth and invasion. Upon invasion, the ECM encountered by breast cancer cells changes from primarily laminin and collagen IV to primarily collagen I. We show here that culturing invasive breast cancer cells in 3-dimensional (3D) collagen I inhibits proliferation through direct regulation of cyclin E1, a G(1)/S regulator that is overexpressed in breast cancer. When the breast cancer cell line MDA-MB-231 was cultured within 3D collagen I gels, the G(1)/S transition was inhibited as compared to cells cultured on conventional 2D collagen or plastic dishes. Cells in 3D collagen downregulated cyclin E1 protein and mRNA, with no change in cyclin D1 level. Cyclin D1 was primarily cytoplasmic in 3D cultures, and this was accompanied by decreased phosphorylation of Rb, a nuclear target for both cyclin E1- and cyclin D1-associated kinases. Positive regulators of cyclin E1 expression, the transcription factor c-Myc and cold-inducible RNA binding protein (CIRP), were decreased in 3D collagen cultures, while the collagen I receptor β1 integrin was greatly increased. Inhibition of β1 integrin function rescued proliferation and cyclin E1 expression as well as c-Myc expression and Rb phosphorylation, but cyclin D1 remained cytoplasmic. We conclude that cyclin E1 is repressed independent of effects on cyclin D1 in a 3D collagen environment and dependent on β1 integrin interaction with collagen I, reducing proliferation of invasive breast cancer cells.

  1. Calycosin Inhibits the Migration and Invasion of Human Breast Cancer Cells by Down-Regulation of Foxp3 Expression

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    Shuangxi Li

    2017-12-01

    Full Text Available Background/Aims: Calycosin, a phytoestrogenic compound, has recently emerged as a promising antitumor drug. It has been shown that calycosin suppresses growth and induces apoptosis of breast cancer cells. However, the effect of calycosin on migration and invasion of breast cancer cells and the underlying molecular mechanisms have not been elucidated. Methods: Human breast cancer cells MCF-7 and T47D were treated with, or without, different doses (0, 6.25, 12.5, 25, 50, 100 or 150 μM of calycosin, and the viability of different groups was determined by MTT assay. Next, the inhibitory effect of higher doses (50, 100 or 150 μM of calycosin on migration and invasion of the two cell lines was determined by wound healing and transwell assay. The relative expression levels of forkhead box P3 (Foxp3, vascular endothelial growth factor (VEGF and matrix metalloproteinase-9 (MMP-9 in MCF-7 and T47D cells were determined by quantitative RT-PCR and Western blot. Results: Treatment with lower doses (6.25 or 12.5 μM promoted proliferation of breast cancer cells, but with higher doses significantly reduced the viability of MCF-7 and T47D cells. Furthermore, higher doses of calycosin were found to inhibit migration and invasion of the two cell lines in a dose-dependent manner. Additionally, treatment with a higher dose of calycosin significantly reduced the expression levels of Foxp3, followed by down-regulation of VEGF and MMP-9 in both MCF-7 and T47D breast cancer cells. Conclusion: Treatment with a higher dose of calycosin tends to reduce migration and invasion capacity of human breast cancer cells, by targeting Foxp3-mediated VEGF and MMP-9 expression.

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

    Directory of Open Access Journals (Sweden)

    Cai Shao-xi

    2011-03-01

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

  3. Development and validation of algorithms to differentiate ductal carcinoma in situ from invasive breast cancer within administrative claims data.

    Science.gov (United States)

    Hirth, Jacqueline M; Hatch, Sandra S; Lin, Yu-Li; Giordano, Sharon H; Silva, H Colleen; Kuo, Yong-Fang

    2018-04-18

    Overtreatment is a common concern for patients with ductal carcinoma in situ (DCIS), but this entity is difficult to distinguish from invasive breast cancers in administrative claims data sets because DCIS often is coded as invasive breast cancer. Therefore, the authors developed and validated algorithms to select DCIS cases from administrative claims data to enable outcomes research in this type of data. This retrospective cohort using invasive breast cancer and DCIS cases included women aged 66 to 70 years in the 2004 through 2011 Texas Cancer Registry (TCR) data linked to Medicare administrative claims data. TCR records were used as "gold" standards to evaluate the sensitivity, specificity, and positive predictive value (PPV) of 2 algorithms. Women with a biopsy enrolled in Medicare parts A and B at 12 months before and 6 months after their first biopsy without a second incident diagnosis of DCIS or invasive breast cancer within 12 months in the TCR were included. Women in 2010 Medicare data were selected to test the algorithms in a general sample. In the TCR data set, a total of 6907 cases met inclusion criteria, with 1244 DCIS cases. The first algorithm had a sensitivity of 79%, a specificity of 89%, and a PPV of 62%. The second algorithm had a sensitivity of 50%, a specificity of 97%. and a PPV of 77%. Among women in the general sample, the specificity was high and the sensitivity was similar for both algorithms. However, the PPV was approximately 6% to 7% lower. DCIS frequently is miscoded as invasive breast cancer, and thus the proposed algorithms are useful to examine DCIS outcomes using data sets not linked to cancer registries. Cancer 2018. © 2018 American Cancer Society. © 2018 American Cancer Society.

  4. 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.

  5. Novel CT and scintigraphic findings of bone metastasis from invasive lobular breast cancer.

    Science.gov (United States)

    Al-Ogaili, Zeyad; Troedson, Russell

    2016-02-01

    The aim of this study is to identify and describe the computed tomography and scintigraphic imaging patterns of osseous metastasis from invasive lobular breast cancer (ILC). CT and skeletal scintigraphy (SS) studies of 23 patients with diagnosis of ILC and osseous metastasis on their initial presentation were reviewed. Osseous metastases in 14 patients (60.8%) appear as uniform small sclerotic lesions (USSL) on CT scan. The SS in these patients were interpreted as negative for metastasis (either normal or with some equivocal findings not typical for metastasis). Osseous metastasis from ILC can have a characteristic imaging pattern on CT and SS. The pattern of USSL on CT scan with negative SS is highly suggestive of osseous metastasis from ILC. © 2015 The Royal Australian and New Zealand College of Radiologists.

  6. Novel CT and scintigraphic findings of bone metastasis from invasive lobular breast cancer

    International Nuclear Information System (INIS)

    Al-Ogaili, Zeyad; Troedson, Russell

    2016-01-01

    The aim of this study is to identify and describe the computed tomography and scintigraphic imaging patterns of osseous metastasis from invasive lobular breast cancer (ILC). CT and skeletal scintigraphy (SS) studies of 23 patients with diagnosis of ILC and osseous metastasis on their initial presentation were reviewed.Osseous metastases in 14 patients (60.8%) appear as uniform small sclerotic lesions (USSL) on CT scan. The SS in these patients were interpreted as negative for metastasis (either normal or with some equivocal findings not typical for metastasis). Osseous metastasis from ILC can have a characteristic imaging pattern on CT and SS. The pattern of USSL on CT scan with negative SS is highly suggestive of osseous metastasis from ILC.

  7. Cdc42 Interacting Protein 4 promotes breast cancer cell invasion and formation of invadopodia through activation of N-WASp

    Science.gov (United States)

    Pichot, Christina S.; Arvanitis, Constadina; Hartig, Sean M.; Jensen, Samuel A.; Bechill, John; Marzouk, Saad; Yu, Jindan; Frost, Jeffrey A.; Corey, Seth J.

    2010-01-01

    In the earliest stages of metastasis, breast cancer cells must reorganize the cytoskeleton to affect cell shape change and promote cell invasion and motility. These events require the cytoskeletal regulators Cdc42 and Rho, their effectors, such as N-WASp/WAVE, and direct inducers of actin polymerization such as Arp2/3. Little consideration has been given to molecules that shape the cell membrane. The F-BAR proteins CIP4, TOCA-1, and FBP17 generate membrane curvature and act as scaffolding proteins for activated Cdc42 and N-WASp. We found that expression of CIP4, but not TOCA-1 or FBP17, was increased in invasive breast cancer cell lines in comparison to weakly or non-invasive breast cancer cell lines. Endogenous CIP4 localized to the leading edge of migrating cells and to invadopodia in cells invading gelatin. Because CIP4 serves as a scaffolding protein for Cdc42, Src, and N-WASp, we tested whether loss of CIP4 could result in decreased N-WASp function. Interaction between CIP4 and N-WASp was EGF-responsive, and CIP4 silencing by siRNA caused decreased tyrosine phosphorylation of N-WASp at a Src-dependent activation site (Y256). CIP4 silencing also impaired the migration and invasion of MDA-MB-231 cells and was associated with decreased formation of invadopodia and gelatin degradation. This study presents a new role for CIP4 in the promotion of migration and invasion of MDA-MB-231 breast cancer cells and establishes the contribution of F-BAR proteins to cancer cell motility and invasion. PMID:20940394

  8. GENOMIC PREDICTOR OF RESPONSE AND SURVIVAL FOLLOWING TAXANE-ANTHRACYCLINE CHEMOTHERAPY FOR INVASIVE BREAST CANCER

    Science.gov (United States)

    Hatzis, Christos; Pusztai, Lajos; Valero, Vicente; Booser, Daniel J.; Esserman, Laura; Lluch, Ana; Vidaurre, Tatiana; Holmes, Frankie; Souchon, Eduardo; Martin, Miguel; Cotrina, José; Gomez, Henry; Hubbard, Rebekah; Chacón, J. Ignacio; Ferrer-Lozano, Jaime; Dyer, Richard; Buxton, Meredith; Gong, Yun; Wu, Yun; Ibrahim, Nuhad; Andreopoulou, Eleni; Ueno, Naoto T.; Hunt, Kelly; Yang, Wei; Nazario, Arlene; DeMichele, Angela; O’Shaughnessy, Joyce; Hortobagyi, Gabriel N.; Symmans, W. Fraser

    2017-01-01

    CONTEXT Accurate prediction of who will (or won’t) have high probability of survival benefit from standard treatments is fundamental for individualized cancer treatment strategies. OBJECTIVE To develop a predictor of response and survival from chemotherapy for newly diagnosed invasive breast cancer. DESIGN Development of different predictive signatures for resistance and response to neoadjuvant chemotherapy (stratified according to estrogen receptor (ER) status) from gene expression microarrays of newly diagnosed breast cancer (310 patients). Then prediction of breast cancer treatment-sensitivity using the combination of signatures for: 1) sensitivity to endocrine therapy, 2) chemo-resistance, and 3) chemo-sensitivity. Independent validation (198 patients) and comparison with other reported genomic predictors of chemotherapy response. SETTING Prospective multicenter study to develop and test genomic predictors for neoadjuvant chemotherapy. PATIENTS Newly diagnosed HER2-negative breast cancer treated with chemotherapy containing sequential taxane and anthracycline-based regimens then endocrine therapy (if hormone receptor-positive). MAIN OUTCOME MEASURES Distant relapse-free survival (DRFS) if predicted treatment-sensitive and absolute risk reduction (ARR, difference in DRFS of the two predicted groups) at median follow-up (3 years), and their 95% confidence intervals (CI). RESULTS Patients in the independent validation cohort (99% clinical Stage II–III) who were predicted to be treatment-sensitive (28% of total) had DRFS of 92% (CI 85–100) and survival benefit compared to others (absolute risk reduction (ARR) 18%; CI 6–28). Predictions were accurate if breast cancer was ER-positive (30% predicted sensitive, DRFS 97%, CI 91–100; ARR 11%, CI 0.1–21) or ER-negative (26% predicted sensitive, DRFS 83%, CI 68–100; ARR 26%, CI 4–28), and were significant in multivariate analysis after adjusting for relevant clinical-pathologic characteristics. Other

  9. Differences in Response and Surgical Management with Neoadjuvant Chemotherapy in Invasive Lobular Versus Ductal Breast Cancer.

    Science.gov (United States)

    Truin, W; Vugts, G; Roumen, R M H; Maaskant-Braat, A J G; Nieuwenhuijzen, G A P; van der Heiden-van der Loo, M; Tjan-Heijnen, V C G; Voogd, A C

    2016-01-01

    This study was conducted to determine the impact of neoadjuvant chemotherapy (NAC) on the likelihood of breast-conserving surgery (BCS) performed for patients with invasive lobular breast carcinoma (ILC) and invasive ductal carcinoma (IDC). Female patients with a diagnosis of ILC or IDC in The Netherlands between July 2008 and December 2012 were identified through the population-based Netherlands Cancer Registry. A total of 466 ILC patients received NAC compared with 3622 IDC patients. Downstaging by NAC was seen in 49.7 % of the patients with ILC and in 69.6 % of the patients with IDC, and a pathologic complete response (pCR) was observed in 4.9 and 20.2 % of these patients, respectively (P Lobular histology was independently associated with a higher mastectomy rate (odds ratio 1.91; 95 % confidence interval 1.49-2.44). Among the patients with clinical T2 and T3 disease, BCS was achieved more often when NAC was administered in ILC as well as IDC. The patients with ILC receiving NAC were less likely to experience a pCR and less likely to undergo BCS than the patients with IDC. With regard to BCS, the impact of NAC for ILC patients was lower than for patients receiving surgery without NAC. However, despite the high number to treating in order to achieve BCS, a small subset of ILC patients, especially cT2 and cT3 patients, still may benefit from NAC.

  10. Lobular carcinomain situof the breast - correlation between minimally invasive biopsy and final pathology.

    Science.gov (United States)

    Szynglarewicz, Bartłomiej; Kasprzak, Piotr; Hałoń, Agnieszka; Matkowski, Rafał

    2017-04-01

    Lobular carcinoma in situ (LCIS) is regarded as a non-obligate precursor of invasive breast cancer (IBC). Hence, the optimal management of LCIS found on minimally invasive breast biopsy remains a subject of debate. The aim of this study was to evaluate the correlation of biopsy findings with postoperative histology and to identify risk factors for upstaging to IBC. Twenty-seven patients with pure LCIS diagnosed on image-guided biopsy (vacuum-assisted or core-needle) underwent subsequent surgery. Clinical, radiological and histological features were compared to the final pathology after surgical excision. Median age of patients was 56 years while median size of LCIS was 15 mm. Final examination demonstrated IBC foci in 29.6% of lesions. Upstaged patients were younger and had larger lesions but without statistical significance ( p = 0.07 and p = 0.09, respectively). Palpable tumours ( p = 0.0004), BIRADS 5 lesions ( p = 0.0001), masses ( p = 0.016) and pleomorphic LCIS ( p = 0.0001) had a significantly increased rate of upstaging. Guidance of the procedure (ultrasound vs. stereotactic) was significantly associated with the upstaging risk ( p = 0.016), while the importance of the biopsy technique (core-needle vs. vacuum-assisted) was not confirmed ( p = 0.37). After excluding pleomorphic LCIS and mass-forming classic LCIS, there was no risk of upstaging for lesions with BIRADS 4 mammographic abnormalities. Pleomorphic histology, mass formation and BIRADS 5 category reflect more aggressive behaviour of LCIS and identify patients who need subsequent surgery. For other patients, close follow-up could be a safe alternative.

  11. Geographic Disparity in the Use of Hypofractionated Radiation Therapy Among Elderly Women Undergoing Breast Conservation for Invasive Breast Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Gillespie, Erin F.; Matsuno, Rayna K.; Xu, Beibei; Triplett, Daniel P.; Hwang, Lindsay; Boero, Isabel J.; Einck, John P.; Yashar, Catheryn; Murphy, James D., E-mail: j2murphy@ucsd.edu

    2016-10-01

    Purpose: To evaluate geographic heterogeneity in the delivery of hypofractionated radiation therapy (RT) for breast cancer among Medicare beneficiaries across the United States. Methods and Materials: We identified 190,193 patients from the Centers for Medicare and Medicaid Services Chronic Conditions Warehouse. The study included patients aged >65 years diagnosed with invasive breast cancer treated with breast conservation surgery followed by radiation diagnosed between 2000 and 2012. We analyzed data by hospital referral region based on patient residency ZIP code. The proportion of women who received hypofractionated RT within each region was analyzed over the study period. Multivariable logistic regression models identified predictors of hypofractionated RT. Results: Over the entire study period we found substantial geographic heterogeneity in the use of hypofractionated RT. The proportion of women receiving hypofractionated breast RT in individual hospital referral regions varied from 0% to 61%. We found no correlation between the use of hypofractionated RT and urban/rural setting or general geographic region. The proportion of hypofractionated RT increased in regions with higher density of radiation oncologists, as well as lower total Medicare reimbursements. Conclusions: This study demonstrates substantial geographic heterogeneity in the use of hypofractionated RT among elderly women with invasive breast cancer treated with lumpectomy in the United States. This heterogeneity persists despite clinical data from multiple randomized trials proving efficacy and safety compared with standard fractionation, and highlights possible inefficiency in health care delivery.

  12. Geographic Disparity in the Use of Hypofractionated Radiation Therapy Among Elderly Women Undergoing Breast Conservation for Invasive Breast Cancer

    International Nuclear Information System (INIS)

    Gillespie, Erin F.; Matsuno, Rayna K.; Xu, Beibei; Triplett, Daniel P.; Hwang, Lindsay; Boero, Isabel J.; Einck, John P.; Yashar, Catheryn; Murphy, James D.

    2016-01-01

    Purpose: To evaluate geographic heterogeneity in the delivery of hypofractionated radiation therapy (RT) for breast cancer among Medicare beneficiaries across the United States. Methods and Materials: We identified 190,193 patients from the Centers for Medicare and Medicaid Services Chronic Conditions Warehouse. The study included patients aged >65 years diagnosed with invasive breast cancer treated with breast conservation surgery followed by radiation diagnosed between 2000 and 2012. We analyzed data by hospital referral region based on patient residency ZIP code. The proportion of women who received hypofractionated RT within each region was analyzed over the study period. Multivariable logistic regression models identified predictors of hypofractionated RT. Results: Over the entire study period we found substantial geographic heterogeneity in the use of hypofractionated RT. The proportion of women receiving hypofractionated breast RT in individual hospital referral regions varied from 0% to 61%. We found no correlation between the use of hypofractionated RT and urban/rural setting or general geographic region. The proportion of hypofractionated RT increased in regions with higher density of radiation oncologists, as well as lower total Medicare reimbursements. Conclusions: This study demonstrates substantial geographic heterogeneity in the use of hypofractionated RT among elderly women with invasive breast cancer treated with lumpectomy in the United States. This heterogeneity persists despite clinical data from multiple randomized trials proving efficacy and safety compared with standard fractionation, and highlights possible inefficiency in health care delivery.

  13. Diagnostic and prognostic relevance of Cullin1 expression in invasive ductal carcinoma of the breast.

    Science.gov (United States)

    Min, Kyueng-Whan; Kim, Dong-Hoon; Do, Sung-Im; Sohn, Jin Hee; Chae, Seoung Wan; Pyo, Jung-Soo; Park, Chan Heun; Oh, Young-Ha; Jang, Ki-Seok; Kim, Hack-Lyoung; Kim, Min

    2012-10-01

    Cullin1 (Cul1) is a matrix degrading enzyme known to be involved in the remodelling of extracellular matrix proteins. This enzyme has recently been reported to play a key role in tumour progression and its presence is associated with poor clinical outcome for several different types of tumours. 159 patients diagnosed with invasive ductal carcinoma between 2000 and 2005 were studied. Cul1 expression was analysed by immunohistochemical staining on a tissue microarray. The relationship between Cul1 expression and clinicopathological parameters was evaluated. Tumour expression of Cul1 was correlated with prognostic factors such as high histological grade and p53 expression, and was also linked to negative ER and positive HER2 as therapeutic markers (all pCul1 expression in both univariate and multivariate analyses (all pCul1 expression was significantly associated with high-grade tumours and poor prognosis, suggesting that it may play a role in breast tumour progression. Cul1 expression may therefore be crucial for the prediction of disease outcome in breast cancer patients.

  14. Stromal cell derived factor-1: its influence on invasiveness and migration of breast cancer cells in vitro, and its association with prognosis and survival in human breast cancer

    International Nuclear Information System (INIS)

    Kang, Hua; Watkins, Gareth; Parr, Christian; Douglas-Jones, Anthony; Mansel, Robert E; Jiang, Wen G

    2005-01-01

    Stromal cell-derived factor (SDF)-1 (CXC chemokine ligand-12) is a member of the CXC subfamily of chemokines, which, through its cognate receptor (CXC chemokine receptor [CXCR]4), plays an important role in chemotaxis of cancer cells and in tumour metastasis. We conducted the present study to evaluate the effect of SDF-1 on the invasiveness and migration of breast cancer cells, and we analyzed the expression of SDF-1 and its relation to clinicopathological features and clinical outcomes in human breast cancer. Expression of SDF-1 mRNA in breast cancer, endothelial (HECV) and fibroblast (MRC5) cell lines and in human breast tissues were studied using RT-PCR. MDA-MB-231 cells were transfected with a SDF-1 expression vector, and their invasiveness and migration was tested in vitro. In addition, the expression of SDF-1 was investigated using immunohistochemistry and quantitative RT-PCR in samples of normal human mammary tissue (n = 32) and mammary tumour (n = 120). SDF-1 expression was identified in MRC5, MDA-MB-435s and MDA-MB-436 cell lines, but CXCR4 expression was detected in all cell lines and breast tissues. An autocrine loop was created following transfection of MDA-MB-231 (which was CXCR4 positive and SDF-1 negative) with a mammalian expression cassette encoding SDF-1 (MDA-MB-231SDF1 +/+ ) or with control plasmid pcDNA4/GFP (MDA-MB-231 +/- ). MDA-MB-231SDF1 +/+ cells exhibited significantly greater invasion and migration potential (in transfected cells versus in wild type and empty MDA-MB-231 +/- ; P < 0.01). In mammary tissues SDF-1 staining was primarily seen in stromal cells and weakly in mammary epithelial cells. Significantly higher levels of SDF-1 were seen in node-positive than in node-negative tumours (P = 0.05), in tumours that metastasized (P = 0.05), and tumours from patients who died (P = 0.03) than in tumours from patients who were disease free. It was most notable that levels of SDF-1 correlated significantly with overall survival (P = 0.001) and

  15. Gamma Imaging-Guided Minimally Invasive Breast Biopsy: Initial Clinical Experience.

    Science.gov (United States)

    Brem, Rachel F; Mehta, Anita K; Rapelyea, Jocelyn A; Akin, Esma A; Bazoberry, Adriana M; Velasco, Christel D

    2018-03-01

    The purpose of this study was to evaluate our initial experience with gamma imaging-guided vacuum-assisted breast biopsy in women with abnormal findings. A retrospective review of patients undergoing breast-specific gamma imaging (BSGI), also known as molecular breast imaging (MBI), between April 2011 and October 2015 found 117 nonpalpable mammographically and sonographically occult lesions for which gamma imaging-guided biopsies were recommended. Biopsy was performed with a 9-gauge vacuum-assisted device with subsequent placement of a titanium biopsy site marker. Medical records and pathologic findings were evaluated. Of the 117 biopsies recommended, 104 were successful and 13 were canceled. Of the 104 performed biopsies, 32 (30.8%) had abnormal pathologic findings. Of those 32 biopsies, nine (28.1%) found invasive cancers, six (18.8%) found ductal carcinoma in situ (DCIS), and 17 (53.1%) found high-risk lesions. Of the 17 high-risk lesions, there were three (17.6%) lobular carcinomas in situ, five (29.4%) atypical ductal hyperplasias, two (11.8%) atypical lobular hyperplasias, one (5.9%) flat epithelial atypia, and six (35.3%) papillomas. Two cases of atypical ductal hyperplasia were upgraded to DCIS at surgery. The overall cancer detection rate for gamma imaging-guided biopsy was 16.3%. In this study, gamma imaging-guided biopsy had a positive predictive value of total successful biopsies of 16.3% for cancer and 30.8% for cancer and high-risk lesions. Gamma imaging-guided biopsy is a viable approach to sampling BSGI-MBI-detected lesions without sonographic or mammographic correlate. Our results compare favorably to those reported for MRI-guided biopsy.

  16. Autocrine/paracrine erythropoietin regulates migration and invasion potential and the stemness of human breast cancer cells

    Science.gov (United States)

    Liang, Ke; Qiu, Songbo; Lu, Yang; Fan, Zhen

    2014-01-01

    Recent studies suggest that erythropoietin (EPO) has pleiotropic effects in several cell types in addition to hematopoietic cells; however, the role of EPO-mediated cell signaling in nonhematopoietic cells, including in cancer cells, remains controversial. Here, we report our findings of autocrine/paracrine production of EPO by breast cancer cells and its functional significance. We detected a significant level of autocrine/paracrine EPO in the conditioned medium from the culture of SKBR3 breast cancer cells, particularly when the cells were cultured in hypoxia. Through knockdown of EPO and EPO receptor expression and experimental elevation of EPO receptor expression in SKBR3 breast cancer cells, we demonstrated novel roles of autocrine/paracrine EPO-mediated cell signaling in regulating migration and invasion potential and stemness-like properties of breast cancer cells. PMID:24100272

  17. Association between invasive ovarian cancer susceptibility and 11 best candidate SNPs from breast cancer genome-wide association study

    DEFF Research Database (Denmark)

    Song, Honglin; Ramus, Susan J; Kjaer, Susanne Krüger

    2009-01-01

    Because both ovarian and breast cancer are hormone-related and are known to have some predisposition genes in common, we evaluated 11 of the most significant hits (six with confirmed associations with breast cancer) from the breast cancer genome-wide association study for association with invasive...... cases and 6308 controls from eight independent studies. Only rs4954956 was significantly associated with ovarian cancer risk both in the replication study and in combined analyses. This association was stronger for the serous histological subtype [per minor allele odds ratio (OR) 1.07 95% CI 1.......01-1.13, P-trend = 0.02 for all types of ovarian cancer and OR 1.14 95% CI 1.07-1.22, P-trend = 0.00017 for serous ovarian cancer]. In conclusion, we found that rs4954956 was associated with increased ovarian cancer risk, particularly for serous ovarian cancer. However, none of the six confirmed breast...

  18. The invasive lobular carcinoma as a prototype luminal A breast cancer: A retrospective cohort study

    Directory of Open Access Journals (Sweden)

    Park In

    2010-12-01

    Full Text Available Abstract Background Although the invasive lobular carcinoma (ILC is the second most frequent histologic subtype in Western countries, its incidence is much lower in Asia, and its characteristics are less well known. Methods We assessed the clinical characteristics and outcomes of 83 Korean patients (2.8% with ILC for comparison with 2,833 (97.2% with the invasive ductal carcinoma (IDC, including 1,088 (37.3% with the luminal A subtype (LA-IDC. Results The mean age of all patients was 48.2 years, with no significant differences among the groups. Compared to IDC, ILC showed a larger tumor size (≥T2, 59.8% vs. 38.8%, P = 0.001, a lower histologic grade (HG 1/2, 90.4% vs. 64.4%, P P P P P P P = 0.57; HR 0.75 for death, 95% CI 0.18-3.09, P = 0.70 and significantly better than for the non-LA-IDC (HR 1.69 for recurrence, 95% CI 1.23-2.33, P = 0.001; HR 1.50 for death, 95% CI 0.97-2.33, P = 0.07. Conclusions ILC, a rare histologic type of breast cancer in Korea, has distinctive clinicopathological characteristics similar to those of LA-IDC.

  19. Rb suppresses collective invasion, circulation and metastasis of breast cancer cells in CD44-dependent manner.

    Directory of Open Access Journals (Sweden)

    Kui-Jin Kim

    Full Text Available Basal-like breast carcinomas (BLCs present with extratumoral lymphovascular invasion, are highly metastatic, presumably through a hematogenous route, have augmented expression of CD44 oncoprotein and relatively low levels of retinoblastoma (Rb tumor suppressor. However, the causal relation among these features is not clear. Here, we show that Rb acts as a key suppressor of multiple stages of metastatic progression. Firstly, Rb suppresses collective cell migration (CCM and CD44-dependent formation of F-actin positive protrusions in vitro and cell-cluster based lymphovascular invasion in vivo. Secondly, Rb inhibits the release of single cancer cells and cell clusters into the hematogenous circulation and subsequent metastatic growth in lungs. Finally, CD44 expression is required for collective motility and all subsequent stages of metastatic progression initiated by loss of Rb function. Altogether, our results suggest that Rb/CD44 pathway is a crucial regulator of CCM and metastatic progression of BLCs and a promising target for anti-BLCs therapy.

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

    Science.gov (United States)

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

    2016-08-01

    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 outcomes. We evaluated the effect of axillary staging procedures and subsequent axillary nodal status in patients with invasive lobular carcinoma (ILC) versus invasive ductal carcinoma (IDC) from 1998 to 2013. The use of SLN biopsy and the nodal status distribution were analyzed in patients with stage T1-T2 ILC and IDC. Logistic regression analysis was performed to determine the independent effect of histologic type on the probability of the presence of isolated tumor cells (ITCs), micrometastases, and macrometastases. A total of 89,971 women were diagnosed, 10,146 with ILC (11%) and 79,825 with IDC (89%). The patients who had undergone SLN biopsy were more frequently diagnosed with ITCs than were those who had undergone axillary lymph node dissection only (odds ratio, 8.8; 95% confidence interval, 7.0-11.2). In 2013, the proportion of patients with ITCs in the axillary nodes was 8% in those with ILC and 4.4% in those with IDC. Patients with ILC were significantly more likely to have ITCs in their axillary lymph nodes than were patients with IDC (odds ratio, 1.8; 95% confidence interval, 1.6-2.0). With the introduction of SLN biopsy and the renewed 2002 TNM classification, patients with ILC have been more frequently diagnosed with ITCs than have patients with IDC. The clinical consequence of this finding must be established from further research. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Correlation between conductivity and prognostic factors in invasive breast cancer using magnetic resonance electric properties tomography (MREPT)

    International Nuclear Information System (INIS)

    Kim, Soo-Yeon; Kim, Min Jung; Kim, Eun-Kyung; Moon, Hee Jung; Yoon, Jung Hyun; Shin, Jaewook; Kim, Dong-Hyun

    2016-01-01

    To investigate the correlation between conductivity and prognostic factors of invasive breast cancer using magnetic resonance electric properties tomography (MREPT). This retrospective study was approved by the Institutional Review Board, and verbal informed consent was obtained prior to breast MRI. This study included 65 women with surgically confirmed invasive breast cancers measuring 1 cm or larger on T2-weighted fast spin echo (FSE). Phase-based MREPT and the coil combination technique were used to reconstruct conductivity. Simple and multiple linear regression analysis were used to find an independent factor associated with conductivity. In total tumours, tumours with HER-2 overexpression showed lower conductivity than those without, and HER-2 overexpression was independently associated with conductivity. In 37 tumours 2 cm or larger, tumours with high mitosis or PR positivity showed higher conductivity than those without, and high mitosis and PR positivity were independently associated with conductivity. In 28 tumours 1-2 cm in size, there were no differences in conductivity according to the prognostic factors. Conductivity values measured using MREPT are associated with the HER-2 overexpression status, and may provide information about mitosis and the PR status of invasive breast cancers 2 cm or larger. (orig.)

  2. Reactivation of HIC-1 gene by saRNA inhibits clonogenicity and invasiveness in breast cancer cells.

    Science.gov (United States)

    Zhao, Feng; Pan, Shengli; Gu, Yan; Guo, Shanyu; Dai, Qiancheng; Yu, Yingyan; Zhang, Wei

    2015-01-01

    Hypermethylated in cancer 1 (HIC-1) is a tumor suppressor gene, which is epigenetically silenced in breast cancer. It is known that the loss of HIC-1, caused by promoter hypermethylation, is associated with tumor aggression and poor survival in breast carcinoma. It has been shown that small activating RNA (saRNA) targeting promoter sequences may induce gene re-expression. In the current study, saRNA was used to restore HIC-1 expression, and the effects on colony formation, invasiveness and the cell cycle in breast cancer cells were explored. dsHIC1-2998, an saRNA, exhibited activating efficacy on MCF-7 and MDA-MB-231 cancer cell lines. A clonogenicity assay showed that evident colony inhibition was induced via saRNA-mediated re-expression of HIC-1 in the two cancer cell lines. Reactivation of HIC-1 significantly inhibited cell migration and invasion, resulting in G0/G1 cell cycle arrest in these cell lines. These findings suggest that HIC-1 may be a potential target in gene therapy for the treatment of breast cancer. saRNA may function as a therapeutic option for upregulating tumor suppressor genes in breast cancer.

  3. EFFECTS OF ESTETROL ON MIGRATION AND INVASION IN T47-D BREAST CANCER CELLS THROUGH THE ACTIN CYTOSKELETON

    Directory of Open Access Journals (Sweden)

    Maria Silvia eGiretti

    2014-05-01

    Full Text Available Estetrol (E4 is a natural human estrogen present at high concentrations during pregnancy. Due to its high oral bioavailability and long plasma half-life, E4 is particularly suitable for therapeutic applications. E4 acts as a selective estrogen receptor modulator, exerting estrogenic actions on the endometrium or the central nervous system, while antagonizing the actions of estradiol in the breast. We tested the effects of E4 on its own or in the presence of 17β-estradiol (E2 on T47-D estrogen receptor (ER positive breast cancer cell migration and invasion of three-dimensional matrices. E4 administration to T47-D cells weakly stimulated migration and invasion. However, E4 decreased the extent of movement and invasion induced by E2. Breast cancer cell movement requires a remodeling of the actin cytoskeleton. During exposure to E4, a weak, concentration-dependent, redistribution of actin fibers towards the cell membrane was observed. However, when E4 was added to E2, a inhibition of actin remodeling induced by E2 was seen. Estrogens stimulate ER+ breast cancer cell movement through the ezrin-radixin-moesin (ERM family of actin regulatory proteins, inducing actin and cell membrane remodeling. E4 was a weak inducer of moesin phosphorylation on Thr558, which accounts for its functional activation. In co-treatment with E2, E4 blocked the activation of this actin controller in a concentration-related fashion. These effects were obtained through recruitment of ERα. In conclusion, E4 acted as a weak estrogen on breast cancer cell cytoskeleton remodeling and movement. However, when E2 was present, E4 counteracted the stimulatory actions of E2. This contributes to the emerging hypothesis that E4 may be a naturally occurring estrogen receptor modulator in the breast.

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

    Science.gov (United States)

    2018-04-06

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

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

    Directory of Open Access Journals (Sweden)

    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.

  6. In vitro regulation of human breast cancer cell adhesion and invasion via integrin receptors to the extracellular matrix.

    Science.gov (United States)

    Gui, G P; Puddefoot, J R; Vinson, G P; Wells, C A; Carpenter, R

    1995-09-01

    The extracellular matrix consists of the interstitium and the basement membrane. Cellular interaction with fibronectin, laminin and collagen provides a possible mechanism by which cancer cells adhere, invade and metastasize. The integrins are a major family of adhesion molecules that recognize epitopes on the extracellular matrix as ligands. These include the alpha 2 beta 1, alpha 3 beta 1, alpha v beta 1 and alpha v beta 5 integrins, most of which were found to be expressed on MCF-7, T47D, MDA-MB-231, ZR75-1 and Hs578T breast cancer cell lines. Each cell line adhered to the matrix proteins in a dose-dependent manner and was inhibited by monoclonal antibodies against relevant integrins. Only Hs578T was significantly invasive through fibronectin but both Hs578T and MDA-MB-231 invaded through laminin and type IV collagen in an in vitro assay. The invasive potential of these cell lines could be inhibited by integrin antibodies added to cells before incubation, but the addition of antibodies after cells were allowed to adhere to the matrix failed to inhibit invasion. Inhibition of cellular adhesion to the matrix reduced the invasive potential of breast cancer cell lines. As integrin antibodies inhibit cell invasion in vitro, the integrins may be of potential value as antitumour therapeutic agents.

  7. Overweight, Obesity, and Postmenopausal Invasive Breast Cancer Risk: A Secondary Analysis of the Women's Health Initiative Randomized Clinical Trials.

    Science.gov (United States)

    Neuhouser, Marian L; Aragaki, Aaron K; Prentice, Ross L; Manson, JoAnn E; Chlebowski, Rowan; Carty, Cara L; Ochs-Balcom, Heather M; Thomson, Cynthia A; Caan, Bette J; Tinker, Lesley F; Urrutia, Rachel Peragallo; Knudtson, Jennifer; Anderson, Garnet L

    2015-08-01

    More than two-thirds of US women are overweight or obese, placing them at increased risk for postmenopausal breast cancer. To investigate in this secondary analysis the associations of overweight and obesity with risk of postmenopausal invasive breast cancer after extended follow-up in the Women's Health Initiative (WHI) clinical trials. The WHI clinical trial protocol incorporated measured height and weight, baseline and annual or biennial mammography, and adjudicated breast cancer end points in 67 142 postmenopausal women ages 50 to 79 years at 40 US clinical centers. The women were enrolled from 1993 to 1998 with a median of 13 years of follow-up through 2010; 3388 invasive breast cancers were observed. Height and weight were measured at baseline, and weight was measured annually thereafter. Data were collected on demographic characteristics, personal and family medical history, and personal habits (smoking, physical activity). Women underwent annual or biennial mammograms. Breast cancers were verified by medical records reviewed by physician adjudicators. Women who were overweight and obese had an increased invasive breast cancer risk vs women of normal weight. Risk was greatest for obesity grade 2 plus 3 (body mass index [BMI], calculated as weight in kilograms divided by height in meters squared, >35.0) (hazard ratio [HR] for invasive breast cancer, 1.58; 95% CI, 1.40-1.79). A BMI of 35.0 or higher was strongly associated with risk for estrogen receptor-positive and progesterone receptor-positive breast cancers (HR, 1.86; 95% CI, 1.60-2.17) but was not associated with estrogen receptor-negative cancers. Obesity grade 2 plus 3 was also associated with advanced disease, including larger tumor size (HR, 2.12; 95% CI, 1.67-2.69; P = .02), positive lymph nodes (HR, 1.89; 95% CI, 1.46-2.45; P = .06), regional and/or distant stage (HR, 1.94; 95% CI, 1.52-2.47; P = .05), and deaths after breast cancer (HR, 2.11; 95% CI, 1.57-2.84; P risk (HR

  8. Breast Tissue Composition and Its Dependence on Demographic Risk Factors for Breast Cancer: Non-Invasive Assessment by Time Domain Diffuse Optical Spectroscopy

    Science.gov (United States)

    Taroni, Paola; Quarto, Giovanna; Pifferi, Antonio; Abbate, Francesca; Balestreri, Nicola; Menna, Simona; Cassano, Enrico; Cubeddu, Rinaldo

    2015-01-01

    Background Breast tissue composition is recognized as a strong and independent risk factor for breast cancer. It is a heritable feature, but is also significantly affected by several other elements (e.g., age, menopause). Nowadays it is quantified by mammographic density, thus requiring the use of ionizing radiation. Optical techniques are absolutely non-invasive and have already proved effective in the investigation of biological tissues, as they are sensitive to tissue composition and structure. Methods Time domain diffuse optical spectroscopy was performed at 7 wavelengths (635-1060 nm) on 200 subjects to derive their breast tissue composition (in terms of water, lipid and collagen content), blood parameters (total hemoglobin content and oxygen saturation level), and information on the microscopic structure (scattering amplitude and power). The dependence of all optically-derived parameters on age, menopausal status, body mass index, and use of oral contraceptives, and the correlation with mammographic density were investigated. Results Younger age, premenopausal status, lower body mass index values, and use of oral contraceptives all correspond to significantly higher water, collagen and total hemoglobin content, and lower lipid content (always p < 0.05 and often p < 10-4), while oxygen saturation level and scattering parameters show significant dependence only on some conditions. Even when age-adjusted groups of subjects are compared, several optically derived parameters (and in particular always collagen and total hemoglobin content) remain significantly different. Conclusions Time domain diffuse optical spectroscopy can probe non-invasively breast tissue composition and physiologic blood parameters, and provide information on tissue structure. The measurement is suitable for in vivo studies and monitoring of changes in breast tissue (e.g., with age, lifestyle, chemotherapy, etc.) and to gain insight into related processes, like the origin of cancer risk

  9. The presence of proliferative breast disease with atypia does not significantly influence outcome in early-stage invasive breast cancer treated with conservative surgery and radiation

    International Nuclear Information System (INIS)

    Fowble, B.; Hanlon, A.L.; Patchefsky, A.; Freedman, G.; Hoffman, J.P.; Sigurdson, E.R.; Goldstein, L.J.

    1998-01-01

    Purpose: To evaluate the influence of the benign background breast-tissue change of atypical hyperplasia (AH) on outcome in patients with early-stage invasive breast cancer treated with conservative surgery and radiation. Materials and Methods: Four hundred and sixty women with Stage I--II breast cancer treated with conservative surgery and radiation from 1982-1994 had pathologic assessment of their background adjacent benign breast tissue. The median follow-up was 5.6 years (range 0.1-15). The median age was 55 years (range 24-88). Of these, 23% had positive axillary nodes; 25% received adjuvant chemotherapy (CMF or CAF) with (9%) or without (17%) tamoxifen. Of the total, 24% received adjuvant tamoxifen alone. The patients were divided into 2 groups: 131 patients with atypical hyperplasia (ductal, 99 patients; lobular, 20 pts; and type not specified, 12 pts), and 329 patients with no proliferative changes or proliferative changes without atypia. Result: A statistically significant difference was observed between the 2 groups for method of detection, primary tumor size, presence of lobular carcinoma in situ (LCIS), pathologic nodal status, region(s) treated with radiation, and type of adjuvant therapy. Patients with atypical hyperplasia (AH) had smaller primary tumors (T1 80% vs. 70%) more often detected solely by mammography (51% vs. 36%) with negative axillary nodes (87% vs. 73%) and radiation treatment to the breast only (93% vs. 78%). LCIS was observed in 9% of the patients with AH and 3% of those without AH. Patients with AH more often received tamoxifen alone (32% vs. 21%), rather than chemotherapy (15% vs. 29%). There were no statistically significant differences between the 2 groups for race, age, menopausal status, family history, histology, histologic subtype DCIS when present, the presence or absence of an extensive intraductal component, final margin status, estrogen or progesterone receptor status, use of re-excision, or total radiation dose to the

  10. LPP is Required for TGF-Beta Induced Motility and Invasion of Neu/ErbB-2 Expressing Breast Cancer Cells

    Science.gov (United States)

    2012-09-01

    cancer cells . Furthermore, we show that focal adhesion targeting of LPP, through its LIM1 domain, is required for the migratory and invasive...phenotypes of ErbB2 positive breast cancer cells in response to TGF Beta. Using Fluorescence Recovery After Photobleaching (FRAP) techniques, we also...have identified LPP as a novel mediator that integrates TGF Beta and ErbB2 signaling to promote the migration and invasion of breast cancer cells . Thus

  11. Tumour characteristics and survival in patients with invasive interval breast cancer classified according to mammographic findings at the latest screening

    DEFF Research Database (Denmark)

    Vitak, B; Olsen, K E; Månson, J C

    1999-01-01

    with invasive interval cancer detected from May 1978 to August 1995 (n = 544). The tumours were evaluated with regard to age, radiological category, interval between the latest screen and diagnosis and tumour characteristics at the time of diagnosis. We investigated possible relationships between the survival...... screen and diagnosis were not genuine predictors of the prognosis in patients with invasive interval breast cancer. No certain prognostic difference existed between true interval cancers and overlooked or misinterpreted interval breast cancers, despite higher proportions of grade-I tumours, ER positive......The aim of this study was to investigate whether different mammographic categories of interval cancer classified according to findings at the latest screening are associated with different distributions of prognostic factors or with different survival rates. The series consisted of all patients...

  12. Salivary Duct Carcinoma and Invasive Ductal Carcinoma of the Breast: A Comparative Immunohistochemical Study.

    Science.gov (United States)

    Jalaly, Jalal B; Sanati, Souzan; Chernock, Rebecca D; Dibe, Dikson G; El-Mofty, Samir K

    2018-01-04

    Salivary duct carcinoma (SDC) is a high-grade salivary gland malignancy with great morphological resemblance to invasive ductal carcinoma (IDC) of the breast. Rarely, female patients may have a past history of both SDC and IDC. When these patients present with distant metastasis, accurate identification of the primary tumor is particularly difficult. Additionally, rare metastasis of SDC to the breast and IDC to the salivary (parotid) gland can also present a diagnostic challenge. Our aim was to develop an immunohistochemical panel that reliably distinguishes SDC from IDC. We included all SDCs diagnosed from 1989 to 2016 (23 cases) and 29 treatment naïve and histologically similar IDCs. All cases were stained with androgen receptor (AR), estrogen receptor-alpha (ER-α), progesterone receptor (PR), HER-2, CK5/6, p63, and beta-catenin. The great majority (> 90%) of both SDCs and IDCs reacted positively to AR. The main discrepancy in the immunohistochemical profiles was a distinctly different reactivity to ER-α, PR and HER-2. While 28 IDCs (96.6%) reacted positively to ER-α and/or PR, the majority expressing both (82.8%) with a moderate to strong staining intensity, only 2 SDCs expressed ER-α (8.7%) and 5 others expressed PR (21.7%) with only one case expressing both (P value SDC (34.8%) were positive for HER-2 while none of the IDCs were positive (P value SDC from IDC. Positive reactivity to ER-α, PR or both and negative HER-2 favors a diagnosis of IDC while ER-α, PR negative, HER-2 positive tumors are more likely SDC.

  13. CLINICAL RELEVANCE OF COEXISTENCE OF DUCTAL CA IN SITU AND INVASIVE DUCTAL CARCINOMA OF BREAST

    Directory of Open Access Journals (Sweden)

    Kirithiga Ramalingam

    2017-06-01

    Full Text Available BACKGROUND There are many studies reported in the literature with respect to the Ductal Carcinoma in Situ (DCIS progressing into Invasive Ductal Carcinoma (IDC of the breast. However, there is hardly any study on the coexistence of both and its clinical significance. The aim of the study is to analyse the clinical and pathological parameters of synchronous DCIS and IDC to predict the prognostic factors. MATERIALS AND METHODS 42 patients with a final pathological diagnosis of synchronous DCIS and IDC diagnosed in 2009-11 were included in the study. Statistical analysis was done using SPSS software utilising the appropriate analytical methods. RESULTS Majority of the patients in this study group presented with early breast cancer (64.3%. Forty eight percent were Her2 subtype (ER, PR negative and HER2/neu-positive and 31% were triple negative. Eighty one percent of the IDC associated histology was Not Otherwise Specified (NOS type. Grade 3 lesions were more common (57%. Recurrence of the disease occurred in 66% of patients during a mean duration of follow up of 3.6 years with predominance of visceral metastasis (51.5%. Recurrence was more common in node positive disease (59.5%, those with lymphovascular emboli (59.5% and perinodal spread (76% on histopathological examination. CONCLUSION Synchronous DCIS and IDC disease entity appears to have an aggressive nature compared to the course of IDC alone entity. Prognostic factors relating to IDC appears to correlate well with recurrence than that of the prognostic factors of DCIS component in such synchronous setting.

  14. Mammographic and ultrasound features of invasive lobular carcinoma of the breast

    International Nuclear Information System (INIS)

    Porter, Alan J.; Evans, Elizabeth B.; Foxcraft, Loani M.; Simpson, Peter T.; Lakhani, Sunil R.

    2014-01-01

    Invasive lobular cancer (ILC) is an important contributor to false negative mammography. This study aims to assess the value of digital mammography and to identify imaging features that could assist the radiologist to suggest the diagnosis of ILC prior to biopsy. Three hundred sixty-one cases of pure ILC diagnosed at the Wesley Breast Clinic during the period 1995–2010 were reviewed by one of the authors (AP). Radiological features were categorized, and clinical features and needle sampling results were recorded. Mammography was negative in 29.9% of ILCs. The commonest positive finding was a localized spiculated mass (41.8%). Thirty-four point nine per cent of lesions were visible in only one view, usually cranio-caudal. Calcification was not a feature of ILC. The use of digital mammography in 30% of cases did not decrease the false negative rate for ILC. Breast ultrasound (BUS) showed an abnormality in 97.8%, most commonly a localized irregular hypoechoic mass with shadowing. Digital mammography does not reduce false negative mammography in ILC. The poor visibility of ILCs may be partly related to their low density (mass/unit volume). ILCs may sometimes be poor attenuators of X-rays but excellent attenuators of ultrasound, causing marked acoustic shadowing. Bilateral whole BUS has a very low false negative rate in experienced hands and is mandatory in symptomatic women. The combination of poor visibility on mammography with high visibility on ultrasound, as well as certain characteristic ultrasound appearances of ILC, may enable the radiologist to suggest ILC as a diagnostic possibility, prior to biopsy.

  15. Mammographic features of screening detected pT1 (a–b) invasive breast cancer using BI-RADS lexicon

    International Nuclear Information System (INIS)

    Bargalló, Xavier; Santamaría, Gorane; Velasco, Martín; Amo, Montse del; Arguis, Pedro; Burrel, Marta; Capurro, Sebastian

    2012-01-01

    Aim: To describe mammographic features in screening detected invasive breast cancer less than or equal to 10 mm using Breast Imaging Reporting and Data System lexicon in full-field digital mammography. Patients and methods: A retrospective analysis of 123 pT1 (a–b) invasive breast cancers in women aged 50–69 years from our screening program. Radiologic patterns were: masses, calcifications, distortions, asymmetries and mixed. Masses: shape, margins and density, and calcifications: morphology, number of flecks and size of the cluster were taken into account, following Breast Imaging Reporting and Data System terminology. Results: We found 61 masses (49.6%), 8 masses with calcifications (6.5%), 30 groups of calcifications (24.4%), 19 architectural distortions (15.4%), 1 architectural distortion with calcifications (0.8%), 4 asymmetries (3.2%). Sixty out of 69 masses were irregular in shape, 6 lobular, 2 ovals and 1 round. Thirty-four showed ill-defined margins, 29 spiculated and 6 microlobulated. Most of them showed a density similar to surrounding fibroglandular tissue. Calcifications were pleomorphic or fine linear in 24 of 30 (80%). Most of cases showed more than 10 flecks and a size greater than 1 cm. Conclusion: The predominant radiologic finding is an irregular, isodense mass those margins tend to share different descriptors, being ill-defined margins the most constant finding. Calcifications representing invasive cancer are predominantly pleomorphic with more than 10 flecks per cm. Architectural distortion and invasive tubular carcinoma are more common than reported in general series

  16. Mammographic features of screening detected pT1 (a–b) invasive breast cancer using BI-RADS lexicon

    Energy Technology Data Exchange (ETDEWEB)

    Bargalló, Xavier, E-mail: xbarga@clinic.ub.es [Department of Radiology (CDIC), Hospital Clínic de Barcelona, C/Villarroel, 170, 08036 Barcelona (Spain); Santamaría, Gorane, E-mail: gsanta@clinic.ub.es [Department of Radiology (CDIC), Hospital Clínic de Barcelona, C/Villarroel, 170, 08036 Barcelona (Spain); Velasco, Martín, E-mail: mvelasco@clinic.ub.es [Department of Radiology (CDIC), Hospital Clínic de Barcelona, C/Villarroel, 170, 08036 Barcelona (Spain); Amo, Montse del, E-mail: mdelamo@clinic.ub.es [Department of Radiology (CDIC), Hospital Clínic de Barcelona, C/Villarroel, 170, 08036 Barcelona (Spain); Arguis, Pedro, E-mail: parguis@clinic.ub.es [Department of Radiology (CDIC), Hospital Clínic de Barcelona, C/Villarroel, 170, 08036 Barcelona (Spain); Burrel, Marta, E-mail: mburrel@clinic.ub.es [Department of Radiology (CDIC), Hospital Clínic de Barcelona, C/Villarroel, 170, 08036 Barcelona (Spain); Capurro, Sebastian, E-mail: scapurro@clinic.ub.es [Department of Radiology (CDIC), Hospital Clínic de Barcelona, C/Villarroel, 170, 08036 Barcelona (Spain)

    2012-10-15

    Aim: To describe mammographic features in screening detected invasive breast cancer less than or equal to 10 mm using Breast Imaging Reporting and Data System lexicon in full-field digital mammography. Patients and methods: A retrospective analysis of 123 pT1 (a–b) invasive breast cancers in women aged 50–69 years from our screening program. Radiologic patterns were: masses, calcifications, distortions, asymmetries and mixed. Masses: shape, margins and density, and calcifications: morphology, number of flecks and size of the cluster were taken into account, following Breast Imaging Reporting and Data System terminology. Results: We found 61 masses (49.6%), 8 masses with calcifications (6.5%), 30 groups of calcifications (24.4%), 19 architectural distortions (15.4%), 1 architectural distortion with calcifications (0.8%), 4 asymmetries (3.2%). Sixty out of 69 masses were irregular in shape, 6 lobular, 2 ovals and 1 round. Thirty-four showed ill-defined margins, 29 spiculated and 6 microlobulated. Most of them showed a density similar to surrounding fibroglandular tissue. Calcifications were pleomorphic or fine linear in 24 of 30 (80%). Most of cases showed more than 10 flecks and a size greater than 1 cm. Conclusion: The predominant radiologic finding is an irregular, isodense mass those margins tend to share different descriptors, being ill-defined margins the most constant finding. Calcifications representing invasive cancer are predominantly pleomorphic with more than 10 flecks per cm. Architectural distortion and invasive tubular carcinoma are more common than reported in general series.

  17. Advanced glycation endproducts increase proliferation, migration and invasion of the breast cancer cell line MDA-MB-231.

    Science.gov (United States)

    Sharaf, Hana; Matou-Nasri, Sabine; Wang, Qiuyu; Rabhan, Zaki; Al-Eidi, Hamad; Al Abdulrahman, Abdulkareem; Ahmed, Nessar

    2015-03-01

    Diabetic patients have increased likelihood of developing breast cancer. Advanced glycation endproducts (AGEs) underlie the pathogenesis of diabetic complications but their impact on breast cancer cells is not understood. This study aims to determine the effects of methylglyoxal-derived bovine serum albumin AGEs (MG-BSA-AGEs) on the invasive MDA-MB-231 breast cancer cell line. By performing cell counting, using wound-healing assay, invasion assay and zymography analysis, we found that MG-BSA-AGEs increased MDA-MB-231 cell proliferation, migration and invasion through Matrigel™ associated with an enhancement of matrix metalloproteinase (MMP)-9 activities, in a dose-dependent manner. Using Western blot and flow cytometry analyses, we demonstrated that MG-BSA-AGEs increased expression of the receptor for AGEs (RAGE) and phosphorylation of key signaling protein extracellular signal-regulated kinase (ERK)-1/2. Furthermore, in MG-BSA-AGE-treated cells, phospho-protein micro-array analysis revealed enhancement of phosphorylation of the ribosomal protein 70 serine S6 kinase beta 1 (p70S6K1), which is known to be involved in protein synthesis, the signal transducer and activator of transcription (STAT)-3 and the mitogen-activated protein kinase (MAPK) p38, which are involved in cell survival. Blockade of MG-BSA-AGE/RAGE interactions using a neutralizing anti-RAGE antibody inhibited MG-BSA-AGE-induced MDA-MB-231 cell processes, including the activation of signaling pathways. Throughout the study, non-modified BSA had a negligible effect. In conclusion, AGEs might contribute to breast cancer development and progression partially through the regulation of MMP-9 activity and RAGE signal activation. The up-regulation of RAGE and the concomitant increased phosphorylation of p70S6K1 induced by AGEs may represent promising targets for drug therapy to treat diabetic patients with breast cancer. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. Intratumoral androgen metabolism and actions in invasive lobular carcinoma of the breast.

    Science.gov (United States)

    Yoda, Tomomi; McNamara, Keely May; Miki, Yasuhiro; Takagi, Mayu; Rai, Yoshiaki; Ohi, Yasuyo; Sagara, Yasuaki; Tamaki, Kentaro; Hirakawa, Hisashi; Ishida, Takanori; Suzuki, Takashi; Ohuchi, Noriaki; Sasano, Hironobu

    2014-11-01

    Invasive lobular carcinoma (ILC) accounts for approximately 10% of all breast carcinomas and is characterized by higher levels of androgen receptor (AR) compared to invasive ductal carcinoma (IDC). Despite this potentially androgen-responsive environment, the combined importance of AR and androgen metabolism in non-neoplastic lobules and lobular carcinoma remains unknown. Therefore, in this study, we evaluated the status of pivotal androgen-producing enzymes 17β-hydroxysteroid dehydrogenase type 5 (17βHSD5) and 5α-reductase type 1 (5αRed1) in 178 cases of ILC and surrounding histologically non-neoplastic lobular tissue using immunohistochemistry. Androgen receptor prevalence was higher but androgenic enzymes lower in ILC than non-neoplastic lobules. In ILC cases the status of 5αRed1 and 17βHSD5 was inversely correlated with tumor size (P = 0.0053) and nuclear grade (P = 0.0290), and significantly associated with better overall survival of the patients (P = 0.0059). Based on these findings, we hypothesized that androgen signaling could act as a tumor suppressor. As previous studies suggested that androgens might partially act by increasing levels of the estrogen inactivating enzyme 17β-hydroxysteroid dehydrogenase type 2 (17βHSD2) in IDC tissues, this was reasonably considered a potential mechanism of androgen actions. Significantly positive correlation was detected between the status of androgenic enzymes and 17βHSD2 (P Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

  19. Lobular histology and response to neoadjuvant chemotherapy in invasive breast cancer.

    Science.gov (United States)

    Lips, Esther H; Mukhtar, Rita A; Yau, Christina; de Ronde, Jorma J; Livasy, Chad; Carey, Lisa A; Loo, Claudette E; Vrancken-Peeters, Marie-Jeanne T F D; Sonke, Gabe S; Berry, Donald A; Van't Veer, Laura J; Esserman, Laura J; Wesseling, Jelle; Rodenhuis, Sjoerd; Shelley Hwang, E

    2012-11-01

    Invasive lobular carcinoma (ILC) has been reported to be less responsive to neoadjuvant chemotherapy (NAC) than invasive ductal carcinoma (IDC). We sought to determine whether ILC histology indeed predicts poor response to NAC by analyzing tumor characteristics such as protein expression, gene expression, and imaging features, and by comparing NAC response rates to those seen in IDC after adjustment for these factors. We combined datasets from two large prospective NAC trials, including in total 676 patients, of which 75 were of lobular histology. Eligible patients had tumors ≥3 cm in diameter or pathologic documentation of positive nodes, and underwent serial biopsies, expression microarray analysis, and MRI imaging. We compared pathologic complete response (pCR) rates and breast conservation surgery (BCS) rates between ILC and IDC, adjusted for clinicopathologic factors. On univariate analysis, ILCs were significantly less likely to have a pCR after NAC than IDCs (11 vs. 25 %, p = 0.01). However, the known differences in tumor characteristics between the two histologic types, including hormone receptor (HR) status, HER2 status, histological grade, and p53 expression, accounted for this difference with the lowest pCR rates among HR+/HER2- tumors in both ILC and IDC (7 and 5 %, respectively). ILC which were HR- and/or HER2+ had a pCR rate of 25 %. Expression subtyping, particularly the NKI 70-gene signature, was correlated with pCR, although the small numbers of ILC in each group precluded significant associations. BCS rate did not differ between IDC and ILC after adjusting for molecular characteristics. We conclude that ILC represents a heterogeneous group of tumors which are less responsive to NAC than IDC. However, this difference is explained by differences in molecular characteristics, particularly HR and HER2, and independent of lobular histology.

  20. Chromosomal aberrations detected by comparative genomic hybridization technique (CGH in invasive ductal carcinoma of breast

    Directory of Open Access Journals (Sweden)

    Nooshiravanpour P

    2007-10-01

    Full Text Available Background: Nonlethal genetic damage is the basis for carcinogenesis. As various gene aberrations accumulate, malignant tumors are formed, regardless of whether the genetic damage is subtle or large enough to be distinguished in a karyotype. The study of chromosomal changes in tumor cells is important in the identification of oncogenes and tumor suppressor genes by molecular cloning of genes in the vicinity of chromosomal aberrations. Furthermore, some specific aberrations can be of great diagnostic and prognostic value. Comparative genomic hybridization (CGH is used to screen the entire genome for the detection and/or location chromosomal copy number changes.Methods: In this study, frozen sections of 20 primary breast tumors diagnosed as invasive ductal carcinoma from the Cancer Institute of Imam Khomeini Hospital, Tehran, Iran, were studied by CGH to detect chromosomal aberrations. We compared histopathological and immunohistochemical findings.Results: Hybridization in four of the cases was not optimal for CGH analysis and they were excluded from the study. DNA copy number changes were detected in 12 (75% of the remaining 16 cases. Twenty-one instances of chromosomal aberrations were detected in total, including: +1q, +17q, +8q, +20q, -13q, -11q, -22q, -1p, -16q, -8p. The most frequent were +1q, +17q, +8q, -13q, similar to other studies. In three cases, we detected -13q, which is associated with axillary lymph node metastasis and was reported in one previous study. The mean numbers of chromosomal aberrations per tumor in metastatic and nonmetastatic tumors was 1.5 and 1, respectively. No other association between detected chromosomal aberrations and histopathological and immunohistochemical findings were seen.Conclusion: Since intermediately to widely invasive carcinomas are more likely to have chromosomal aberrations, CGH can be a valuable prognostic tool. Furthermore, CGH can be used to detect targeting molecules within novel amplifications

  1. Divergent effects of insulin-like growth factor-1 receptor expression on prognosis of estrogen receptor positive versus triple negative invasive ductal breast carcinoma

    NARCIS (Netherlands)

    Hartog, Hermien; Horlings, Hugo M; van der Vegt, Bert; Kreike, Bas; Ajouaou, Abderrahim; van de Vijver, Marc J; Boezen, Hendrika; de Bock, Geertruida H; van der Graaf, Wilhelmina; Wesseling, Jelle

    2011-01-01

    The insulin-like growth factor type 1 receptor (IGF1R) is involved in progression of breast cancer and resistance to systemic treatment. Targeting IGF1R signaling may, therefore, be beneficial in systemic treatment. We report the effect of IGF1R expression on prognosis in invasive ductal breast

  2. The anticancer potential of steroidal saponin, dioscin, isolated from wild yam (Dioscorea villosa) root extract in invasive human breast cancer cell line MDA-MB-231 in vitro

    Science.gov (United States)

    Previously, we observed that wild yam (Dioscorea villosa) root extract (WYRE) was able to activate GATA3 in human breast cancer cells targeting epigenome. This study aimed to 'nd out if dioscin (DS), a bioactive compound of WYRE, can modulate GATA3 functions and cellular invasion in human breast can...

  3. Polyphenol-rich strawberry extract (PRSE) shows in vitro and in vivo biological activity against invasive breast cancer cells.

    Science.gov (United States)

    Amatori, Stefano; Mazzoni, Luca; Alvarez-Suarez, Josè Miguel; Giampieri, Francesca; Gasparrini, Massimiliano; Forbes-Hernandez, Tamara Yuliett; Afrin, Sadia; Errico Provenzano, Alfredo; Persico, Giuseppe; Mezzetti, Bruno; Amici, Augusto; Fanelli, Mirco; Battino, Maurizio

    2016-08-08

    We describe the biological effects of a polyphenol-rich strawberry extract (PRSE), obtained from the "Alba" variety, on the highly aggressive and invasive basal-like breast cancer cell line A17. Dose-response and time-course experiments showed that PRSE is able to decrease the cellular viability of A17 cells in a time- and dose-dependent manner. PRSE effect on cell survival was investigated in other tumor and normal cell lines of both mouse and human origin, demonstrating that PRSE is more active against breast cancer cells. Cytofluorimetric analysis of A17 cells demonstrated that sub-lethal doses of PRSE reduce the number of cells in S phase, inducing the accumulation of cells in G1 phase of cell cycle. In addition, the migration of A17 cells was studied monitoring the ability of PRSE to inhibit cellular mobility. Gene expression analysis revealed the modulation of 12 genes playing different roles in the cellular migration, adhesion and invasion processes. Finally, in vivo experiments showed the growth inhibition of A17 cells orthotopically transplanted into FVB syngeneic mice fed with PRSE. Overall, we demonstrated that PRSE exerts important biological activities against a highly invasive breast cancer cell line both in vitro and in vivo suggesting the strawberry extracts as preventive/curative food strategy.

  4. 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.

  5. PCP4/PEP19 promotes migration, invasion and adhesion in human breast cancer MCF-7 and T47D cells.

    Science.gov (United States)

    Yoshimura, Takuya; Hamada, Taiji; Hijioka, Hiroshi; Souda, Masakazu; Hatanaka, Kazuhito; Yoshioka, Takako; Yamada, Sohsuke; Tsutsui, Masato; Umekita, Yoshihisa; Nakamura, Norifumi; Tanimoto, Akihide

    2016-08-02

    Purkinje cell protein (PCP) 4/peptide (PEP) 19 is expressed in Purkinje cells where it has a calmodulin-binding, anti-apoptotic function. We recently demonstrated that PCP4/PEP19 is expressed and inhibit apoptosis in human breast cancer cell lines. In the present study we investigated the role of PCP4/PEP19 in cell morphology, adhesion, migration, and invasion in MCF-7 and T47D human breast cancer cell lines. Knockdown of PCP4/PEP19 reduced the formation of filopodia-like cytoplasmic structures and vinculin expression, and enhanced E-cadherin expression. Activities of migration, invasion, and cell adhesion were also decreased after the knockdown of PCP4/PEP19 in MCF-7 and T47D cells. These results suggested that PCP4/PEP19 promotes cancer cell adhesion, migration, and invasion and that PCP4/PEP19 may be a potential target for therapeutic agents in breast cancer treatment which act by inhibiting epithelial-mesenchymal transition and enhancing apoptotic cell death.

  6. Heat shock protein 90β stabilizes focal adhesion kinase and enhances cell migration and invasion in breast cancer cells

    International Nuclear Information System (INIS)

    Xiong, Xiangyang; Wang, Yao; Liu, Chengmei; Lu, Quqin; Liu, Tao; Chen, Guoan; Rao, Hai; Luo, Shiwen

    2014-01-01

    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

  7. 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.

  8. Is there an association between invasive lobular carcinoma of the breast and a family history of gastric cancer?

    Science.gov (United States)

    Chikman, Bar; Davidson, Tima; Kais, Hasan; Jeroukhimov, Igor; Leshno, Ari; Sandbank, Judith; Halevy, Ariel; Lavy, Ron

    2016-01-01

    CDH1 gene mutations have been found to be associated with diffuse type gastric cancer and invasive lobular carcinoma (ILC) of the breast. To the best of our knowledge, this is the only study relating a family history of gastric cancer to ILC of the breast. We conducted a retrospective study comparing the family history of malignancies in patients with invasive ductal carcinoma (IDC) of the breast and ILC treated in our Medical Center. The comparison was evaluated in both types of breast cancer groups, dividing the patients into two age groups, cancer was reported in 7.2 % in the ILC group as compared to 2.3 % in the IDC group, P cancer was more common in the ILC group as opposed to the IDC group, 18 versus 8.1 % respectively, P = 0.002 and persisted in both age groups. We conclude that a family history of malignancies in first degree relatives is more common in patients with ILC than IDC and that there is a significant association between a family history of gastric cancer and ILC.

  9. RNAi-mediated knockdown of FANCF suppresses cell proliferation, migration, invasion, and drug resistance potential of breast cancer cells

    Directory of Open Access Journals (Sweden)

    L. Zhao

    2014-01-01

    Full Text Available Fanconi anemia complementation group F protein (FANCF is a key factor, which maintains the function of FA/BRCA, a DNA damage response pathway. However, the functional role of FANCF in breast cancer has not been elucidated. We performed a specific FANCF-shRNA knockdown of endogenous FANCF in vitro. Cell viability was measured with a CCK-8 assay. DNA damage was assessed with an alkaline comet assay. Apoptosis, cell cycle, and drug accumulation were measured by flow cytometry. The expression levels of protein were determined by Western blot using specific antibodies. Based on these results, we used cell migration and invasion assays to demonstrate a crucial role for FANCF in those processes. FANCF shRNA effectively inhibited expression of FANCF. We found that proliferation of FANCF knockdown breast cancer cells (MCF-7 and MDA-MB-435S was significantly inhibited, with cell cycle arrest in the S phase, induction of apoptosis, and DNA fragmentation. Inhibition of FANCF also resulted in decreased cell migration and invasion. In addition, FANCF knockdown enhanced sensitivity to doxorubicin in breast cancer cells. These results suggest that FANCF may be a potential target for molecular, therapeutic intervention in breast cancer.

  10. Resveratrol suppresses migration, invasion and stemness of human breast cancer cells by interfering with tumor-stromal cross-talk.

    Science.gov (United States)

    Suh, Jinyoung; Kim, Do-Hee; Surh, Young-Joon

    2018-04-02

    Cancer-associated fibroblasts (CAFs) constitute a major compartment of the tumor microenvironment. CAFs produce a variety of cytokines, growth factors and extracellular matrix proteins, thereby stimulating tumor progression. CAFs are distinct from normal fibroblasts for their overexpression of α-smooth muscle actin. Recent studies suggest that CAFs play an important role in proliferation and migration of cancer cells through cross-talk with them. Resveratrol (trans-3,4'5,-trihydroxystilbene), a phytoalexin present in grapes, has been reported to possess chemopreventive and chemotherapeutic activities. In the present study, we examined the effects of resveratrol on CAF-induced migration, invasion and self-renewal activity of breast cancer cells. Resveratrol inhibited proliferation, migration and invasion of human breast cancer cells treated with CAF-conditioned media (CAF-CM). Resveratrol treatment suppressed the CAF-CM-induced expression of Cyclin D1, c-Myc, MMP-2 and MMP-9. In addition, resveratrol inhibited Sox2 expression as well as activation of Akt and STAT3 induced by CAF-CM in breast cancer cells. Further, resveratrol abrogated stemness properties and reduced the expression of self-renewal signaling molecules in stem-like breast cancer cells. Taken together, the present study provides insights into the role of resveratrol in tumor microenvironment with focus on interaction between cancer cells and the hosting niche. Copyright © 2018 Elsevier Inc. All rights reserved.

  11. RNAi-mediated knockdown of FANCF suppresses cell proliferation, migration, invasion, and drug resistance potential of breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, L.; Li, N.; Yu, J.K.; Tang, H.T.; Li, Y.L.; He, M.; Yu, Z.J.; Bai, X.F. [Department of Pharmacology, School of Pharmacy, China Medical University, Heping Ward, Shenyang City, Liaoning (China); Zheng, Z.H.; Wang, E.H. [Institute of Pathology and Pathophysiology, China Medical University, Heping Ward, Shenyang City, Liaoning (China); Wei, M.J. [Department of Pharmacology, School of Pharmacy, China Medical University, Heping Ward, Shenyang City, Liaoning (China)

    2013-12-12

    Fanconi anemia complementation group F protein (FANCF) is a key factor, which maintains the function of FA/BRCA, a DNA damage response pathway. However, the functional role of FANCF in breast cancer has not been elucidated. We performed a specific FANCF-shRNA knockdown of endogenous FANCF in vitro. Cell viability was measured with a CCK-8 assay. DNA damage was assessed with an alkaline comet assay. Apoptosis, cell cycle, and drug accumulation were measured by flow cytometry. The expression levels of protein were determined by Western blot using specific antibodies. Based on these results, we used cell migration and invasion assays to demonstrate a crucial role for FANCF in those processes. FANCF shRNA effectively inhibited expression of FANCF. We found that proliferation of FANCF knockdown breast cancer cells (MCF-7 and MDA-MB-435S) was significantly inhibited, with cell cycle arrest in the S phase, induction of apoptosis, and DNA fragmentation. Inhibition of FANCF also resulted in decreased cell migration and invasion. In addition, FANCF knockdown enhanced sensitivity to doxorubicin in breast cancer cells. These results suggest that FANCF may be a potential target for molecular, therapeutic intervention in breast cancer.

  12. Active and passive cigarette smoking and mortality among Hispanic and non-Hispanic white women diagnosed with invasive breast cancer.

    Science.gov (United States)

    Boone, Stephanie D; Baumgartner, Kathy B; Baumgartner, Richard N; Connor, Avonne E; John, Esther M; Giuliano, Anna R; Hines, Lisa M; Rai, Shesh N; Riley, Elizabeth C; Pinkston, Christina M; Wolff, Roger K; Slattery, Martha L

    2015-11-01

    Women who smoke at breast cancer diagnosis have higher risk of breast cancer-specific and all-cause mortality than nonsmokers; however, differences by ethnicity or prognostic factors and risk for noncancer mortality have not been evaluated. We examined associations of active and passive smoke exposure with mortality among Hispanic (n = 1020) and non-Hispanic white (n = 1198) women with invasive breast cancer in the Breast Cancer Health Disparities Study (median follow-up of 10.6 years). Risk of breast cancer-specific (HR = 1.55, 95% CI = 1.11-2.16) and all-cause (HR = 1.68, 95% CI = 1.30-2.17) mortality was increased for current smokers, with similar results stratified by ethnicity. Ever smokers had an increased risk of noncancer mortality (HR = 1.68, 95% CI = 1.12-2.51). Associations were strongest for current smokers who smoked for 20 years or more were postmenopausal, overweight and/or obese, or reported moderate and/or high alcohol consumption; however, interactions were not significant. Breast cancer-specific mortality was increased two fold for moderate and/or high recent passive smoke exposure among never smokers (HR = 2.12, 95% CI = 1.24-3.63). Findings support associations of active-smoking and passive-smoking diagnosis with risk of breast cancer-specific and all-cause mortality and ever smoking with noncancer mortality, regardless of ethnicity, and other factors. Smoking is a modifiable lifestyle factor and effective smoking cessation, and maintenance programs should be routinely recommended for women with breast cancer. Copyright © 2015 Elsevier Inc. All rights reserved.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  14. PAX2 is activated by estradiol in breast cancer cells of the luminal subgroup selectively, to confer a low invasive phenotype

    Science.gov (United States)

    2011-01-01

    Background Metastasis is the leading cause of death among breast cancer patients. Identifying key cellular factors controlling invasion and metastasis of breast cancer cells should pave the way to new therapeutic strategies efficiently interfering with the metastatic process. PAX2 (paired box 2) transcription factor is expressed by breast cancer cells in vivo and recently, it was shown to negatively regulate the expression of ERBB2 (erythroblastic leukemia viral oncogene homolog 2, HER-2/neu), a well-documented pro-invasive and pro-metastastic gene, in luminal/ERalpha-positive (ERα+) breast cancer cells. The objective of the present study was to investigate a putative role for PAX2 in the control of luminal breast cancer cells invasion, and to begin to characterize its regulation. Results PAX2 activity was higher in cell lines from luminal compared to non-luminal subtype, and activation of PAX2 by estradiol was selectively achieved in breast cancer cell lines of the luminal subtype. This process was blocked by ICI 182780 and could be antagonized by IGF-1. Knockdown of PAX2 in luminal MCF-7 cells completely abrogated estradiol-induced downregulation of ERBB2 and decrease of cell invasion, whereas overexpression of PAX2 in these cells enhanced estradiol effects on ERBB2 levels and cell invasion. Conclusions The study demonstrates that PAX2 activation by estradiol is selectively achieved in breast cancer cells of the luminal subtype, via ERα, and identifies IGF-1 as a negative regulator of PAX2 activity in these cells. Further, it reveals a new role for PAX2 in the maintenance of a low invasive behavior in luminal breast cancer cells upon exposure to estradiol, and shows that overexpression and activation of PAX2 in these cells is sufficient to reduce their invasive ability. PMID:22168360

  15. The impact of postmastectomy radiotherapy on local control in patients with invasive lobular breast cancer

    International Nuclear Information System (INIS)

    Diepenmaat, Lindy A.; Sangen, Maurice J.C. van der; Poll-Franse, Lonneke V. van de; Beek, Mike W.P.M. van; Berlo, Charles L.H. van; Luiten, Ernest J.T.; Nieuwenhuijzen, Grard A.P.; Voogd, Adri C.

    2009-01-01

    Purpose: The aim of this population-based study was to examine the impact of postmastectomy radiotherapy on the risk of local recurrence in patients with invasive lobular breast cancer (ILC). Methods: The population-based Eindhoven Cancer Registry was used to select all patients with ILC, who underwent mastectomy in five general hospitals in the southern part of Netherlands between 1995 and 2002. Of the 499 patients 383 patients fulfilled the eligibility criteria. Of these patients, 170 (44.4%) had received postmastectomy radiotherapy. The median follow-up was 7.2 years. Fourteen patients (3.7%) were lost to follow-up. Results: During follow-up 22 patients developed a local recurrence, of whom 4 had received postmastectomy radiotherapy. The 5-year actuarial risk of local recurrence was 2.1% for the patients with and 8.7% for the patients without postmastectomy radiotherapy. After adjustment for age at diagnosis, tumour stage and adjuvant systemic treatment, the patients who underwent postmastectomy radiotherapy were found to have a more than 3 times lower risk of local recurrence compared to the patients without (Hazard Ratio 0.30; 95% Confidence Interval: 0.10-0.89). Conclusion: Local control is excellent for patients with ILC who undergo postmastectomy radiotherapy and significantly better than for patients not receiving radiotherapy.

  16. Association of C-MYC amplification with progression from the in situ to the invasive stage in C-MYC-amplified breast carcinomas

    NARCIS (Netherlands)

    Robanus-Maandag, Els C.; Bosch, Cathy A. J.; Kristel, Petra M.; Hart, Augustinus A. M.; Faneyte, Ian F.; Nederlof, Petra M.; Peterse, Johannes L.; van de Vijver, Marc J.

    2003-01-01

    Human carcinoma in situ of the breast already demonstrates genomic changes found in invasive lesions. However, no specific genetic alterations have previously been identified that are associated with progression from the in situ to the invasive stage. By comparative genomic hybridization (CGH) and

  17. Broccoli and watercress suppress matrix metalloproteinase-9 activity and invasiveness of human MDA-MB-231 breast cancer cells

    International Nuclear Information System (INIS)

    Rose, Peter; Huang, Qing; Ong, Choon Nam; Whiteman, Matt

    2005-01-01

    A high dietary intake of cruciferous vegetables has been associated with a reduction in numerous human pathologies particularly cancer. In the current study, we examined the inhibitory effects of broccoli (Brassica oleracea var. italica) and watercress (Rorripa nasturtium aquaticum) extracts on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced cancer cell invasion and matrix metalloproteinase-9 activity using human MDA-MB-231 breast cancer cells. Aberrant overexpression of matrix metalloproteinases, including metalloproteinase-9, is associated with increased invasive potential in cancer cell lines. Our results demonstrate that extracts of broccoli and Rorripa suppressed TPA-induced MMP-9 activity and invasiveness in a concentration dependant manner as determined by zymographic analysis. Furthermore, fractionation of individual extracts followed by liquid chromatography mass spectroscopy analysis (LC-MS) revealed that the inhibitory effects of each vegetable were associated with the presence of 4-methysulfinylbutyl (sulforaphane) and 7-methylsulphinylheptyl isothiocyanates. Taken together, our data indicate that isothiocyanates derived form broccoli and Rorripa inhibit metalloproteinase 9 activities and also suppress the invasive potential of human MDA-MB-231 breast cancer cells in vitro. The inhibitory effects observed in the current study may contribute to the suppression of carcinogenesis by diets high in cruciferous vegetables

  18. Evaluation of aqueous extracts of Taraxacum officinale on growth and invasion of breast and prostate cancer cells.

    Science.gov (United States)

    Sigstedt, Sophia C; Hooten, Carla J; Callewaert, Manika C; Jenkins, Aaron R; Romero, Anntherese E; Pullin, Michael J; Kornienko, Alexander; Lowrey, Timothy K; Slambrouck, Severine Van; Steelant, Wim F A

    2008-05-01

    Ethnotraditional use of plant-derived natural products plays a significant role in the discovery and development of potential medicinal agents. Plants of the genus Taraxacum, commonly known as dandelions, have a history of use in Chinese, Arabian and Native American traditional medicine, to treat a variety of diseases including cancer. To date, however, very few studies have been reported on the anti-carcinogenic activity of Taraxacum officinale (TO). In the present study, three aqueous extracts were prepared from the mature leaves, flowers and roots, and investigated on tumor progression related processes such as proliferation and invasion. Our results show that the crude extract of dandelion leaf (DLE) decreased the growth of MCF-7/AZ breast cancer cells in an ERK-dependent manner, whereas the aqueous extracts of dandelion flower (DFE) and root (DRE) had no effect on the growth of either cell line. Furthermore, DRE was found to block invasion of MCF-7/AZ breast cancer cells while DLE blocked the invasion of LNCaP prostate cancer cells, into collagen type I. Inhibition of invasion was further evidenced by decreased phosphorylation levels of FAK and src as well as reduced activities of matrix metalloproteinases, MMP-2 and MMP-9. This study provides new scientific data on TO and suggests that TO extracts or individual components present in the extracts may be of value as novel anti-cancer agents.

  19. Exosome-bound WD repeat protein Monad inhibits breast cancer cell invasion by degrading amphiregulin mRNA.

    Directory of Open Access Journals (Sweden)

    Makio Saeki

    Full Text Available Increased stabilization of mRNA coding for key cancer genes can contribute to invasiveness. This is achieved by down-regulation of exosome cofactors, which bind to 3'-UTR in cancer-related genes. Here, we identified amphiregulin, an EGFR ligand, as a target of WD repeat protein Monad, a component of R2TP/prefoldin-like complex, in MDA-MB-231 breast cancer cells. Monad specifically interacted with both the 3'-UTR of amphiregulin mRNA and the RNA degrading exosome, and enhanced decay of amphiregulin transcripts. Knockdown of Monad increased invasion and this effect was abolished with anti-amphiregulin neutralizing antibody. These results suggest that Monad could prevent amphiregulin-mediated invasion by degrading amphiregulin mRNA.

  20. Relationship between morphological features and kinetic patterns of enhancement of the dynamic breast magnetic resonance imaging and clinico-pathological and biological factors in invasive breast cancer

    International Nuclear Information System (INIS)

    Fernández-Guinea, Oscar; Andicoechea, Alejandro; González, Luis O; González-Reyes, Salomé; Merino, Antonio M; Hernández, Luis C; López-Muñiz, Alfonso; García-Pravia, Paz; Vizoso, Francisco J

    2010-01-01

    To investigate the relationship between the magnetic resonance imaging (MRI) features of breast cancer and its clinicopathological and biological factors. Dynamic MRI parameters of 68 invasive breast carcinomas were investigated. We also analyzed microvessel density (MVD), estrogen and progesterone receptor status, and expression of p53, HER2, ki67, VEGFR-1 and 2. Homogeneous enhancement was significantly associated with smaller tumor size (T1: < 2 cm) (p = 0.015). Tumors with irregular or spiculated margins had a significantly higher MVD than tumors with smooth margins (p = 0.038). Tumors showing a maximum enhancement peak at two minutes, or longer, after injecting the contrast, had a significantly higher MVD count than those which reached this point sooner (p = 0.012). The percentage of tumors with vascular invasion or high mitotic index was significantly higher among those showing a low percentage (≤ 150%) of maximum enhancement before two minutes than among those ones showing a high percentage (>150%) of enhancement rate (p = 0.016 and p = 0.03, respectively). However, there was a significant and positive association between the mitotic index and the peak of maximum intensity (p = 0.036). Peritumor inflammation was significantly associated with washout curve type III (p = 0.042). Variations in the early phase of dynamic MRI seem to be associated with parameters indicatives of tumor aggressiveness in breast cancer

  1. Smurf2 E3 ubiquitin ligase modulates proliferation and invasiveness of breast cancer cells in a CNKSR2 dependent manner.

    Science.gov (United States)

    David, Diana; Jagadeeshan, Sankar; Hariharan, Ramkumar; Nair, Asha Sivakumari; Pillai, Radhakrishna Madhavan

    2014-01-01

    Smurf2 is a member of the HECT family of E3 ubiquitin ligases that play important roles in determining the competence of cells to respond to TGF- β/BMP signaling pathway. However, besides TGF-β/BMP pathway, Smurf2 regulates a repertoire of other signaling pathways ranging from planar cell polarity during embryonic development to cell proliferation, migration, differentiation and senescence. Expression of Smurf2 is found to be dysregulated in many cancers including breast cancer. The purpose of the present study is to examine the effect of Smurf2 knockdown on the tumorigenic potential of human breast cancer cells emphasizing more on proliferative signaling pathway. siRNAs targeting different regions of the Smurf2 mRNA were employed to knockdown the expression of Smurf2. The biological effects of synthetic siRNAs on human breast cancer cells were investigated by examining the cell proliferation, migration, invasion, focus formation, anchorage-independent growth, cell cycle arrest, and cell cycle and cell proliferation related protein expressions upon Smurf2 silencing. Smurf2 silencing in human breast cancer cells resulted in a decreased focus formation potential and clonogenicity as well as in vitro cell migration/invasion capabilities. Moreover, knockdown of Smurf2 suppressed cell proliferation. Cell cycle analysis showed that the anti-proliferative effect of Smurf2 siRNA was mediated by arresting cells in the G0/G1 phase, which was caused by decreased expression of cyclin D1and cdk4, followed by upregulation p21 and p27. Furthermore, we demonstrated that silencing of Smurf2 downregulated the proliferation of breast cancer cells by modulating the PI3K- PTEN-AKT-FoxO3a pathway via the scaffold protein CNKSR2 which is involved in RAS-dependent signaling pathways. The present study provides the first evidence that silencing Smurf2 using synthetic siRNAs can regulate the tumorigenic properties of human breast cancer cells in a CNKSR2 dependent manner. Our results

  2. Our approach for breast cancer screening using both mammography and echography, with special reference to detection of nonpalpable minute invasive cancer

    International Nuclear Information System (INIS)

    Takebe, Koji; Izumori, Ayumi; Yasumo, Naomi

    2007-01-01

    We present the results of our approach for breast cancer screening using both mammography and echography. A total of 4,632 participants underwent screening with our own combined method using mammography and echography at our clinic during a two-year period in 2005 and 2006. Recall studies were carried out in 364 women (recall rate, 79%), and breast cancer was detected in 36 women (cancer detection rate, 0.78%). When the detected cancers were classified histopathologically, 22 were invasive ductal cancers and the remaining 14 were non-invasive cancers. Of the 22 women who proved to have invasive cancers, 14 had been unaware of their tumors, which were non-palpable. If an invasive cancer is overlooked, the consequences may be more serious than if a non-invasive cancer is missed, because the former is can be potentially fatal. In order to decrease breast cancer mortality, invasive cancers must be detected when they are small. Since we were able to detect many small and non-palpable breast cancers that had not been noticed by the participants, our current breast cancer screening system appears to be more efficient for life-saving than other systems. (author)

  3. [Lack of progesterone receptor expression predicts poor prognosis in patients with operable ER-positive invasive breast cancer].

    Science.gov (United States)

    Ma, R M; Chen, C Z; Lin, C Q; Zhang, W; Guo, G L

    2016-09-23

    To investigate the impact of lack of progesterone receptor (PR) expression on the prognosis of patients with operable ER (estrogen receptor)-positive invasive breast cancer. We retrospectively analyzed the clinicopathological features, treatment and survival data of 318 women with ER+ /PR+ and ER+ /PR- invasive breast cancer. Among the 318 patients, there were 219 PR-positive and 99 PR-negative cases. The 5-year overall survival (OS) rate was 92.5%, and the 5-year disease-free survival (DFS) rate was 87.2% in the 318 ER-positive patients. Among them, the 5-year OS rates were significantly different between the PR-positive group (94.6%) and PR-negative group (87.8%, P=0.020), and the 5-year DFS rates were also significantly different from each other (89.8% and 81.6%, respectively, P=0.019). Univariate analysis showed that PR status, tumor size, T stage, axillary lymph node metastasis, and clinical stage were prognostic factors for OS (Plack of PR expression, T stage ≥2, and positive axillary lymph node metastasis were independent risk factors for poor DFS and OS in ER-positive breast cancer patients (Plack of PR expression was not significant in predicting poor DFS or OS when patients were in stage Ⅰ or with a small tumor (≤2 cm) (P>0.05 for all), and also showed that premenopausal women with PR-negative disease had poorer DFS and OS than PR-positive patients (PLack of PR expression is an independent risk factor for poor prognosis in patients with operable ER-positive invasive breast cancer, especially in patients with a large tumor (>2 cm), advanced clinical stage (Stage Ⅱ or Ⅲ) or in premenopausal status.

  4. BOLD-MRI of breast invasive ductal carcinoma: correlation of R2* value and the expression of HIF-1{alpha}

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Min; Guo, Xiaojuan; Wang, Shuangkun [Capital Medical University, Department of Radiology, Beijing Chao Yang Hospital, Beijing (China); Jin, Mulan; Wang, Ying [Capital Medical University Beijing, Department of Pathology, Beijing Chaoyang Hospital, Beijing (China); Li, Jie; Liu, Jun [Capital Medical University Beijing, Department of Breast Surgery, Beijing Chaoyang Hospital, Beijing (China)

    2013-12-15

    To explore the reliability and feasibility of blood oxygenation level-dependent-based functional magnetic resonance imaging (BOLD-fMRI) to depict hypoxia in breast invasive ductal carcinoma. A total of 103 women with 104 invasive ductal carcinomas (IDCs) underwent breast BOLD-fMRI at 3.0 T. Histological specimens were analysed for tumour size, grade, axillary lymph nodes and expression of oestrogen receptors, progesterone receptors, human epidermal growth factor receptor 2, p53, Ki-67 and hypoxia inducible factor 1{alpha} (HIF-1{alpha}). The distribution and reliability of R2* were analysed. Correlations of the R2* value with the prognostic factors and HIF-1{alpha} were respectively analysed. The R2* map of IDC demonstrated a relatively heterogeneous signal. The mean R2* value was (53.4 {+-} 18.2) Hz. The Shapiro-Wilk test (W = 0.971, P = 0.020) suggested that the sample did not follow a normal distribution. The inter-rater and intrarater correlation coefficient was 0.967 and 0.959, respectively. The R2* values of IDCs were significantly lower in patients without axillary lymph nodes metastasis. The R2* value had a weak correlation with Ki67 expression (r = 0.208, P = 0.038). The mean R2* value correlated moderately with the level of HIF-1{alpha} (r = 0.516, P = 0.000). BOLD-fMRI is a simple and non-invasive technique that yields hypoxia information on breast invasive ductal carcinomas. (orig.)

  5. Mammographic casting-type calcification associated with small screen-detected invasive breast cancers: is this a reliable prognostic indicator?

    Energy Technology Data Exchange (ETDEWEB)

    Peacock, C.; Given-Wilson, R.M. E-mail: rosalind.given-wilson@stgeorges.nhs.uk; Duffy, S.W

    2004-02-01

    AIM: The aim of the present study was to establish whether mammographic casting-type calcification associated with small screen-detected invasive breast cancers is a reliable prognostic indicator. METHODS AND MATERIALS: We retrospectively identified 50 consecutive women diagnosed with an invasive cancer less than 15 mm who showed associated casting calcification on their screening mammograms. Controls were identified that showed no microcalcification and were matched for tumour size, histological type and lymph node status. A minimum of 5 years follow-up was obtained, noting recurrence and outcome. Conditional and unconditional logistic regression, depending on the outcome variable, were used to analyse the data, taking the matched design into account in both cases. Where small numbers prohibited the use of logistic regression, Fisher's exact test was used. RESULTS: Five deaths from breast cancer occurred out of the 50 cases, of which three were lymph node positive, two were lymph node negative and none were grade 3. None of the 78 control cases died from breast cancer. The difference in breast cancer death rates was significant by Fisher's exact test (p=0.02). Risk of recurrence was also significantly increased in the casting cases (OR=3.55, 95% CI 1.02-12.33, p=0.046). CONCLUSION: Although the overall outcome for small screen-detected breast cancers is good, our study suggests that casting calcification is a poorer prognostic factor. The advantage of a mammographic feature as an independent prognostic indicator lies in early identification of high-risk patients, allowing optimization of management.

  6. Prognostic significance of basal-like phenotype and fascin expression in node-negative invasive breast carcinomas.

    Science.gov (United States)

    Rodríguez-Pinilla, Socorro María; Sarrió, David; Honrado, Emiliano; Hardisson, David; Calero, Francisco; Benitez, Javier; Palacios, José

    2006-03-01

    Basal-like phenotype tumors are frequently found among BRCA1 germ-line mutated breast carcinomas. They are biologically aggressive and have a tendency towards visceral metastasis when untreated. Nevertheless, it has been suggested that they respond to chemotherapy better than other types of tumors. Fascin expression has been associated with lung metastasis in breast cancer. The aim of this study was to determine whether basal-like phenotype and fascin were related in both sporadic and familial tumors and with prognosis in node-negative sporadic breast cancers. 230 nonfamilial and 28 hereditary node-negative invasive breast carcinomas were immunohistochemically analyzed using tissue microarrays. Tumors that were estrogen receptor/HER2 negative and cytokeratin 5/6 and/or epidermal growth factor receptor positive were considered to have a basal-like phenotype. A basal-like phenotype was found in 11.9% of sporadic cancers. Among patients not receiving adjuvant chemotherapy, a basal-like phenotype was associated with poor prognosis (P = 0.001, log-rank test) whereas no such association was found in patients receiving it. Tumors with a basal-like phenotype showed local recurrence (17.4%) or visceral metastasis (13%) but not bone metastasis (P = 0.001). Fascin expression was observed in 25.1% of sporadic invasive breast carcinomas and was associated with the basal-like phenotype, but not with prognosis or recurrence pattern. Fascin was expressed in 83.3% and 16.7% BRCA1- and BRCA2-associated carcinomas, respectively (P = 0.048). Basal-like tumors had a tendency towards visceral metastasis and their prognosis was dependent on the use of postoperative chemotherapy. Although fascin expression was associated with the basal-like phenotype, it was not associated with their metastatic behavior. Fascin expression is frequent in BRCA1-associated tumors.

  7. Zinc presence in invasive ductal carcinoma of the breast and its correlation with oestrogen receptor status

    International Nuclear Information System (INIS)

    Farquharson, M J; Al-Ebraheem, A; Geraki, K; Leek, R; Jubb, A; Harris, A L

    2009-01-01

    Zinc is known to play an important role in many cellular processes, and the levels of zinc are controlled by specific transporters from the ZIP (SLC39A) influx transporter group and the ZnT (SLC30A) efflux transporter group. The distribution of zinc was measured in 59 samples of invasive ductal carcinoma of breast using synchrotron radiation micro probe x-ray fluorescence facilities. The samples were formalin fixed paraffin embedded tissue micro arrays (TMAs) enabling a high throughput of samples and allowing us to correlate the distribution of trace metals with tumour cell distribution and, for the first time, important biological variables. The samples were divided into two classes, 34 oestrogen receptor positive (ER+ve) and 25 oestrogen receptor negative (ER-ve) based on quantitative immunohistochemistry assessment. The overall levels of zinc (i.e. in tumour and surrounding tissue) in the ER+ve samples were on average 60% higher than those in the ER-ve samples. The zinc levels were higher in the ER+ve tumour areas compared to the ER-ve tumour areas with the mean levels in the ER+ve samples being approximately 80% higher than the mean ER-ve levels. However, the non-tumour tissue regions of the samples contained on average the same levels of zinc in both types of breast cancers. The relative levels of zinc in tumour areas of the tissue were compared with levels in areas of non-tumour surrounding tissue. There was a significant increase in zinc in the tumour regions of the ER+ve samples compared to the surrounding regions (P < 0.001) and a non-significant increase in the ER-ve samples. When comparing the increase in zinc in the tumour regions expressed as a percentage of the surrounding non-tumour tissue zinc level in the same sample, a significant difference between the ER+ve and ER-ve samples was found (P < 0.01).

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

    International Nuclear Information System (INIS)

    Jiang, Jiahua; Jedinak, Andrej; Sliva, Daniel

    2011-01-01

    Highlights: ► Ganodermanontriol (GDNT), a Ganoderma mushroom alcohol, inhibits growth of breast cancer cells. ► CDC20 is over-expressed in tumors but not in the tumor surrounding tissue in breast cancer patients. ► GDNT inhibits expression of CDC20 in breast cancer cells. ► GDNT inhibits cell adhesion, cell migration and cell invasion of breast cancer cells. ► 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.

  9. 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.

  10. Invasive lobular carcinoma of the male breast: A rare histology of an uncommon disease

    International Nuclear Information System (INIS)

    Upadhyay, R.; Kumar, P.; Sharma, D.N.; Haresh, K.P.; Gupta, S.; Julka, P.K.; Rath, G.K.; Bhankar, H.

    2016-01-01

    Male breast carcinoma is a rare malignancy comprising less than 1% of all breast cancers. It is a serious disease with most patients presenting in advanced stages. Infiltrating ductal carcinoma is the most common histology while lobular carcinoma represents less than 1% of all these tumors. We report a case of locally advanced lobular carcinoma of breast in a 60 year old male

  11. The invasive lobular carcinoma as a prototype luminal A breast cancer: A retrospective cohort study

    International Nuclear Information System (INIS)

    Jung, So-Youn; Lee, Seeyoun; Kim, Seok Won; Kang, Han-Sung; Ro, Jungsil; Jeong, Junsoo; Shin, Seung-Ho; Kwon, Youngmee; Kim, Eun-A; Ko, Kyoung Lan; Shin, Kyung Hwan; Lee, Keun Seok; Park, In Hae

    2010-01-01

    Although the invasive lobular carcinoma (ILC) is the second most frequent histologic subtype in Western countries, its incidence is much lower in Asia, and its characteristics are less well known. We assessed the clinical characteristics and outcomes of 83 Korean patients (2.8%) with ILC for comparison with 2,833 (97.2%) with the invasive ductal carcinoma (IDC), including 1,088 (37.3%) with the luminal A subtype (LA-IDC). The mean age of all patients was 48.2 years, with no significant differences among the groups. Compared to IDC, ILC showed a larger tumor size (≥T2, 59.8% vs. 38.8%, P = 0.001), a lower histologic grade (HG 1/2, 90.4% vs. 64.4%, P < 0.001), more frequent estrogen receptor positive (90.4% vs. 64.4%, P < 0.001), progesterone receptor positive (71.1% vs. 50.1%, P < 0.001) and HER2 negative (97.5% vs. 74.6%, P < 0.001) status, and lower Ki-67 expression (10.3% ± 10.6% vs. 20.6% ± 19.8%, P < 0.001), as well as being more likely to be of the luminal A subtype (91.4% vs. 51.2%, P < 0.001). Six (7.2%) ILC and 359 (12.7%) IDC patients developed disease recurrence, with a median follow-up of 56.4 (range 4.9-136.6) months. The outcome of ILC was close to LA-IDC (HR 0.77 for recurrence, 95% CI 0.31-1.90, P = 0.57; HR 0.75 for death, 95% CI 0.18-3.09, P = 0.70) and significantly better than for the non-LA-IDC (HR 1.69 for recurrence, 95% CI 1.23-2.33, P = 0.001; HR 1.50 for death, 95% CI 0.97-2.33, P = 0.07). ILC, a rare histologic type of breast cancer in Korea, has distinctive clinicopathological characteristics similar to those of LA-IDC

  12. Specific sites of metastases in invasive lobular carcinoma: a retrospective cohort study of metastatic breast cancer.

    Science.gov (United States)

    Inoue, Masayuki; Nakagomi, Hiroshi; Nakada, Haruka; Furuya, Kazushige; Ikegame, Kou; Watanabe, Hideki; Omata, Masao; Oyama, Toshio

    2017-09-01

    Invasive lobular carcinoma (ILC) is known to be the second most common histological type following invasive ductal carcinoma (IDC). Definitive clinical features of ILC are controversial. We retrospectively analyzed a cohort of 330 patients with metastatic breast cancer, 303 of IDC, 19 of ILC, and 8 of others. We compared the patient age and tumor-node-metastasis factors, disease-free survival (DFS), estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor 2 (HER2) expression at the primary site between ILC and IDC. We then selected the patients in the ER + or PR + /HER2 - subtype specifically and compared sites of recurrence, and the survival curve starting from the point of development of metastatic disease. The clinical stage was significantly higher in the ILC patients than in the IDC (p = 0.001). The mean (±SD) of DFS for the ILC and IDC patients was 2.6 ± 0.6 and 2.4 ± 0.3 years, respectively, with no significant difference (p = 0.18). However, the hormone receptor status was same between both groups; the rate of HER2 positivity was significantly lower in the ILC group (0%) than in the IDC group (16.2%) (p = 0.05). In ER + or PR + /HER2 - subtype, the mean DFS for the ILC and IDC was 2.9 ± 0.6 and 3.1 ± 0.3 years, and the median survival time after the recurrence for ILC and IDC patients was 4.2 ± 0.7 and 5.6 ± 0.7 years, respectively, with no significant difference (p = 0.77). The frequency of lung metastases was significantly lower in the ILC group (6.3%) than in the IDC group (53.7%) (p cancer patients with ILC. We need to reveal the definitive feature of ILC and develop new therapeutic strategies to prevent the dissemination of ILCs.

  13. Broccoli Sprout Extract in Treating Patients With Breast Cancer

    Science.gov (United States)

    2017-08-30

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

  14. Bmi-1 promotes invasion and metastasis, and its elevated expression is correlated with an advanced stage of breast cancer

    Science.gov (United States)

    2011-01-01

    Background B-lymphoma Moloney murine leukemia virus insertion region-1 (Bmi-1) acts as an oncogene in various tumors, and its overexpression correlates with a poor outcome in several human cancers. Ectopic expression of Bmi-1 can induce epithelial-mesenchymal transition (EMT) and enhance the motility and invasiveness of human nasopharyngeal epithelial cells (NPECs), whereas silencing endogenous Bmi-1 expression can reverse EMT and reduce the metastatic potential of nasopharyngeal cancer cells (NPCs). Mouse xenograft studies indicate that coexpression of Bmi-1 and H-Ras in breast cancer cells can induce an aggressive and metastatic phenotype with an unusual occurrence of brain metastasis; although, Bmi-1 overexpression did not result in oncogenic transformation of MCF-10A cells. However, the underlying molecular mechanism of Bmi-1-mediated progression and the metastasis of breast cancer are not fully elucidated at this time. Results Bmi-1 expression is more pronouncedly increased in primary cancer tissues compared to matched adjacent non-cancerous tissues. High Bmi-1 expression is correlated with advanced clinicopathologic classifications (T, N, and M) and clinical stages. Furthermore, a high level of Bmi-1 indicates an unfavorable overall survival and serves as a high risk marker for breast cancer. In addition, inverse transcriptional expression levels of Bmi-1 and E-cadherin are detected between the primary cancer tissues and the matched adjacent non-cancerous tissues. Higher Bmi-1 levels are found in the cancer tissue, whereas the paired adjacent non-cancer tissue shows higher E-cadherin levels. Overexpression of Bmi-1 increases the motility and invasive properties of immortalized human mammary epithelial cells, which is concurrent with the increased expression of mesenchymal markers, the decreased expression of epithelial markers, the stabilization of Snail and the dysregulation of the Akt/GSK3β pathway. Consistent with these observations, the repression of Bmi

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

    Science.gov (United States)

    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.

  16. HER2 evaluation using the novel rabbit monoclonal antibody SP3 and CISH in tissue microarrays of invasive breast carcinomas.

    Science.gov (United States)

    Ricardo, Sara Alexandra Vinhas; Milanezi, Fernanda; Carvalho, Sílvia Teresa; Leitão, Dina Raquel Aguilera; Schmitt, Fernando Carlos Lander

    2007-09-01

    Laboratory methods for HER2 assessment currently include immunohistochemical (IHC) methods (measuring protein overexpression) and fluorescence in situ hybridisation (FISH) (measuring gene amplification). The measure of HER2 protein by IHC is usually assessed by the mouse monoclonal antibody CB11, and polyclonal antibodies (Herceptest) directed against the internal portion of the receptor. Recently, chromogenic in situ hybridisation (CISH), in which HER2 is detected by a peroxidase reaction and the gene amplification can be determined by regular bright-field microscopy, has emerged as an alternative to FISH. To evaluate the status of HER2 in tissue microarrays (TMAs) of invasive breast cancer using the novel rabbit monoclonal antibody SP3 directed against the external portion of HER2, and correlate the results with CB11 and CISH. IHC was performed with two antibodies (CB11 and SP3) and CISH for HER2 in 10 TMA blocks with 190 formalin-fixed paraffin-embedded cases of invasive breast carcinomas. The correlation between SP3 and CB11 was significant (pCISH (pCISH, shows that this novel antibody is a reliable candidate to evaluate the expression of HER2 in breast cancer.

  17. Nogo-B receptor expression correlates negatively with malignancy grade and ki-67 antigen expression in invasive ductal breast carcinoma.

    Science.gov (United States)

    Pula, Bartosz; Olbromski, Mateusz; Owczarek, Tomasz; Ambicka, Aleksandra; Witkiewicz, Wojciech; Ugorski, Maciej; Rys, Janusz; Zabel, Maciej; Dziegiel, Piotr; Podhorska-Okolow, Marzena

    2014-09-01

    Nogo-B receptor (NgBR) has been shown to be involved in endothelial cell chemotaxis and morphogenesis. However, few studies analyzing its expression in cancer cells have been performed. We examined NgBR expression in 233 patients with invasive ductal breast carcinoma (IDC) and corresponding non-malignant breast tissues (NMBT) on mRNA (real-time polymerase chain reaction) and protein levels (immunohistochemistry; IHC and western-blot analysis). NgBR expression was found also analyzed in breast cancer cell lines of varying invasiveness. NgBR expression was increased in IDC compared to NMBT on the mRNA (p=0.0007) and protein level (p=0.018). NgBR expression decreased significantly with IDC malignancy grade and correlated negatively with the Ki-67 antigen expression (r=-0.18; p=0.0005). High NgBR mRNA expression was associated with estrogen receptor negativity (p=0.0023) and the triple-negative phenotype of the tumors (p=0.0129). NgBR may be involved in IDC development, however, its role in its progression requires further research. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  18. Automated image analysis of cyclin D1 protein expression in invasive lobular breast carcinoma provides independent prognostic information.

    Science.gov (United States)

    Tobin, Nicholas P; Lundgren, Katja L; Conway, Catherine; Anagnostaki, Lola; Costello, Sean; Landberg, Göran

    2012-11-01

    The emergence of automated image analysis algorithms has aided the enumeration, quantification, and immunohistochemical analyses of tumor cells in both whole section and tissue microarray samples. To date, the focus of such algorithms in the breast cancer setting has been on traditional markers in the common invasive ductal carcinoma subtype. Here, we aimed to optimize and validate an automated analysis of the cell cycle regulator cyclin D1 in a large collection of invasive lobular carcinoma and relate its expression to clinicopathologic data. The image analysis algorithm was trained to optimally match manual scoring of cyclin D1 protein expression in a subset of invasive lobular carcinoma tissue microarray cores. The algorithm was capable of distinguishing cyclin D1-positive cells and illustrated high correlation with traditional manual scoring (κ=0.63). It was then applied to our entire cohort of 483 patients, with subsequent statistical comparisons to clinical data. We found no correlation between cyclin D1 expression and tumor size, grade, and lymph node status. However, overexpression of the protein was associated with reduced recurrence-free survival (P=.029), as was positive nodal status (Pinvasive lobular carcinoma. Finally, high cyclin D1 expression was associated with increased hazard ratio in multivariate analysis (hazard ratio, 1.75; 95% confidence interval, 1.05-2.89). In conclusion, we describe an image analysis algorithm capable of reliably analyzing cyclin D1 staining in invasive lobular carcinoma and have linked overexpression of the protein to increased recurrence risk. Our findings support the use of cyclin D1 as a clinically informative biomarker for invasive lobular breast cancer. Copyright © 2012 Elsevier Inc. All rights reserved.

  19. Histopathological Features of Non-Neoplastic Breast Parenchyma Do Not Predict BRCA Mutation Status of Patients with Invasive Breast Cancer

    Directory of Open Access Journals (Sweden)

    Soley Bayraktar

    2015-01-01

    Full Text Available Background Several studies have evaluated histologic features of nonneoplastic breast parenchyma in patients with BRCA1/2 mutations, but the results are conflicting. The limited data suggest a much higher prevalence of high-risk precursor lesions in BRCA carriers. Therefore, we designed this study to compare the clinicopathological characteristics of peritumoral benign breast tissue in patients with and without deleterious BRCA mutations. Methods Women with breast cancer (BC who were referred for genetic counseling and underwent BRCA genetic testing in 2010 and 2011 were included in the study. Results Of the six benign histological features analyzed in this study, only stromal fibrosis grade 2/3 was found to be statistically different, with more BRCA noncarriers having stromal fibrosis grade 2/3 than BRCA1/2 carriers ( P = 0.04. Conclusion There is no significant association between mutation risk and the presence of benign histologic features of peritumoral breast parenchyma.

  20. Elucidation of the Molecular Mechanisms for Aberrant Expression of Breast Cancer Specific Gene 1 in Invasive and Metastatic Breast Carcinomas

    National Research Council Canada - National Science Library

    Liu, Jingwen

    2005-01-01

    ...%) of tumor tissues of diversified cancer types including liver, esophagus, colon, gastric, lung, prostate, cervical, and breast cancer but rarely expressed in tumor matched non neoplastic adjacent tissues (NNAT) (0.6...

  1. Ductal carcinoma in situ diagnosed at US-guided 14-gauge core-needle biopsy for breast mass: Preoperative predictors of invasive breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Park, Ah Young; Gweon, Hye Mi; Son, Eun Ju; Yoo, Miri; Kim, Jeong-Ah; Youk, Ji Hyun, E-mail: jhyouk@yuhs.ac

    2014-04-15

    Objectives: To identify preoperative features that could be used to predict invasive breast cancer in women with a diagnosis of ductal carcinoma in situ (DCIS) at ultrasound (US)-guided 14-gauge core needle biopsy (CNB). Methods: A total of 86 DCIS lesions that were diagnosed at US-guided 14-gauge CNB and excised surgically in 84 women were assessed. We retrospectively reviewed the patients’ medical records, mammography, US, and MR imaging. We compared underestimation rates of DCIS for the collected clinical and radiologic variables and determined the preoperative predictive factors for upstaging to invasive cancer. Results: Twenty-seven (31.4%) of 86 DCIS lesions were upgraded to invasive cancer. Preoperative features that showed a significantly higher underestimation of DCIS were palpability or nipple discharge (p = 0.040), number of core specimens less than 5 (p = 0.011), mammographic maximum lesion size of 25 mm or larger (p = 0.022), mammographic mass size of 40 mm or larger (p = 0.046), sonographic mass size of 32 mm or larger (p = 0.009), lesion size of 30 mm on MR (p = 0.004), lower signal intensity (SI) on fat-saturated T2-weighted MR images (FS-T2WI) (p = 0.005), heterogeneous or rim enhancement on MR images (p = 0.009), and apparent diffusion coefficient (ADC) values lower than 1.04 × 10{sup −3} mm{sup 2}/s on diffusion-weighted MR imaging (DWI) (p < 0.001). Conclusion: Clinical symptom of palpability or nipple discharge, number of core specimen, mammographic maximum lesion or mass size, SI on FS-T2WI, heterogeneous or rim enhancement on MR, and ADC value may be helpful in predicting the upgrade to invasive breast cancer for DCIS diagnosed at US-guided 14-gauge CNB.

  2. Effect of Interval to Definitive Breast Surgery on Clinical Presentation and Survival in Early-Stage Invasive Breast Cancer

    International Nuclear Information System (INIS)

    Vujovic, Olga; Yu, Edward; Cherian, Anil; Perera, Francisco; Dar, A. Rashid; Stitt, Larry; Hammond, A.

    2009-01-01

    Purpose: To examine the effect of clinical presentation and interval to breast surgery on local recurrence and survival in early-stage breast cancer. Methods and Materials: The data from 397 patients with Stage T1-T2N0 breast carcinoma treated with conservative surgery and breast radiotherapy between 1985 and 1992 were reviewed at the London Regional Cancer Program. The clinical presentation consisted of a mammogram finding or a palpable lump. The intervals from clinical presentation to definitive breast surgery used for analysis were 0-4, >4-12, and >12 weeks. The Kaplan-Meier estimates of the time to local recurrence, disease-free survival, and cause-specific survival were determined for the three groups. Cox regression analysis was used to evaluate the effect of clinical presentation and interval to definitive surgery on survival. Results: The median follow-up was 11.2 years. No statistically significant difference was found in local recurrence as a function of the interval to definitive surgery (p = .424). A significant difference was noted in disease-free survival (p = .040) and cause-specific survival (p = .006) with an interval of >12 weeks to definitive breast surgery. However, the interval to definitive surgery was dependent on the presentation for cause-specific survival, with a substantial effect for patients with a mammographic presentation and a negligible effect for patients with a lump presentation (interaction p = .041). Conclusion: The results of this study suggest that an interval of >12 weeks to breast surgery might be associated with decreased survival for patients with a mammographic presentation, but it appeared to have no effect on survival for patients presenting with a palpable breast lump.

  3. Comparison of intraoperative frozen section analysis for sentinel lymph node biopsy during breast cancer surgery for invasive lobular carcinoma and invasive ductal carcinoma

    Directory of Open Access Journals (Sweden)

    Povoski Stephen P

    2009-03-01

    Full Text Available Abstract Background Sentinel lymph node (SLN biopsy is the standard of care for the surgical assessment of the axilla during breast cancer surgery. However, the diagnostic accuracy of intraoperative frozen section analysis for confirming metastatic involvement of SLNs in cases of invasive lobular carcinoma (ILC versus that of invasive ductal carcinoma (IDC has generated controversy secondary to a frequently low-grade cytologic appearance and an often discohesive pattern displayed by metastatic lymph nodes in ILC. In the current report, we present a comparison of intraoperative frozen section analysis for confirming the presence of metastatic disease within SLNs during breast cancer surgery for ILC and IDC. Methods We evaluated the results of 131 consecutive cases of ILC from 1997 to 2008 and 133 cases of IDC (selected by a random sequence generator program from amongst 1163 consecutive cases of IDC from the same time period. All cases had at least one SLN that had both intraoperative frozen section analysis and confirmatory permanent section analysis performed. Results No statistically significant difference was found in the sensitivity (67% vs. 75%, P = 0.385, specificity (100% vs. 100%, accuracy (86% vs. 92%, P = 0.172, false negative rate (33% vs. 25%, P = 0.385, negative predictive value (81% vs. 89%, P = 0.158, and positive predictive value (100% vs. 100% for frozen section analysis for confirming the presence of metastatic disease within SLNs during breast cancer surgery for ILC and IDC. Conclusion Since there was no statistically significant difference in sensitivity, specificity, accuracy, false negative rate, negative predictive value, and positive predictive value between frozen section analysis of SLNs for patients with ILC and IDC, the clinical accuracy of confirming metastatic involvement of SLNs on frozen section analysis for ILC should not be considered inferior to the clinical accuracy for IDC. Therefore, frozen section analysis

  4. Outcomes in women with invasive ductal or invasive lobular early stage breast cancer treated with anastrozole or exemestane in CCTG (NCIC CTG) MA.27.

    Science.gov (United States)

    Strasser-Weippl, K; Sudan, G; Ramjeesingh, R; Shepherd, L E; O'Shaughnessy, J; Parulekar, W R; Liedke, P E R; Chen, B E; Goss, P E

    2018-02-01

    Histological subtype, (invasive ductal breast cancer (IDBC)/invasive lobular breast cancer (ILBC)), might be a marker for differential response to endocrine therapy in breast cancer. Clinical trial MA.27 compared 5 years of adjuvant anastrozole or exemestane in postmenopausal patients with hormone receptor positive early breast cancer. We evaluated IDBC versus ILBC (based on original pathology reports) as predictor for event-free survival (EFS) and overall survival (OS). A total of 5709 patients (5021 with IDBC and 688 with ILBC) were included (1876 were excluded because of missing or other histological subtype). Median follow-up was 4.1 years. Overall, histological subtype did not influence OS or EFS (HR (hazard ratio) 1.14, 95% confidence interval (CI) [0.79-1.63], P = 0.49 and HR 1.04, 95% CI [0.77-1.41], P = 0.81, respectively). There was no significant difference in OS between treatment with exemestane versus treatment with anastrozole in the IDBC group (HR = 0.92, 95% CI [0.73-1.16], P = 0.46). In the ILBC group, a marginally significant difference in favour of treatment with anastrozole was seen (HR = 1.79, 95% CI [0.98-3.27], P = 0.055). In multivariable analysis a prognostic effect of the interaction between treatment and histological subtype on OS (but not on EFS) was noted, suggesting a better outcome for patients with ILBC on anastrozole (HR 2.1, 95% CI [0.99-4.29], P = 0.05). After stepwise selection in the multivariable model, a marginally significant prognostic effect for the interaction variable (treatment with histological subtype) on OS (but not on EFS) was noted (Ratio of HR 2.1, 95% CI [1.00-4.31], P = 0.05). Our data suggest an interaction effect between treatment and histology (P = 0.05) on OS. Here, patients with ILBC cancers had a better OS when treated with anastrozole versus exemestane, whereas no difference was noted for patients with IDBC. NCT00066573. Crown Copyright © 2017. Published by Elsevier Ltd. All rights

  5. Contribution of germline mutations in cancer predisposition genes to tumor etiology in young women diagnosed with invasive breast cancer.

    Science.gov (United States)

    Rummel, Seth K; Lovejoy, Leann; Shriver, Craig D; Ellsworth, Rachel E

    2017-08-01

    Although breast cancer in young women accounts for cancer predisposition genes is needed to improve the understanding of breast cancer etiology in young women. All female patients enrolled in the Clinical Breast Cancer Project between 2001 and 2015 and diagnosed with invasive breast cancer before age 40 were included in this study. Family history was classified using the NCCN Familial Risk Assessment guidelines. Targeted sequencing of 94 cancer predisposition genes was performed using peripheral blood DNA. Variants were detected using VariantStudio and classified using ClinVar. Seven percent (141/1980) of patients were young women and 44 had a significant family history. Sequencing was completed for 118 women with genomic DNA. Pathogenic mutations were present in 27 patients: BRCA1 (n = 10), BRCA2 (n = 12), TP53 (n = 1), and CHEK2 (n = 4). Mutations classified as pathogenic were also detected in APC (n = 1) and MUTYH (n = 2). Variants of uncertain significance (VUS) were detected in an additional 17 patients in ten genes. Pathogenic mutations in high- and moderate-risk breast cancer genes were detected in 23% of young women with an additional 3% having pathogenic mutations in colon cancer predisposition genes. VUS were observed in 14% of women in genes such as ATM, BRCA2, CDH1, CHEK2, and PALB2. Identification of those non-genetic factors is critical to reduce the burden of breast cancer in this population.

  6. Effect of Hydrochloric Acid Decalcification on Expression Pattern of Prognostic Markers in Invasive Breast Carcinomas.

    Science.gov (United States)

    Maclary, Shawn C; Mohanty, Sambit K; Bose, Shikha; Chung, Fai; Balzer, Bonnie L

    2017-02-01

    In the United States, it is estimated that 100,000 people are living with metastatic breast cancer (BC) with bone representing the most common site of involvement. However, patients with isolated bone metastasis at presentation may have a longer survival. Therapeutic options for BC bone metastases often include systemic anticancer therapy (endocrine, chemotherapy, monoclonal antibodies, and/or other targeted therapies), which is largely dependent on the immunohistochemical (IHC) repertoire of the cancer for the prognostic markers [estrogen (ER) and progesterone receptors (PR), Ki-67, p53, and Her-2/neu] at its osseous metastatic site. Traditionally, specimens obtained from the bone metastasis require decalcification, which may affect the immunoreactivity of these prognostic markers. To the best of our knowledge, limited studies describe the effect of decalcification on immunoexpression of the above-mentioned markers. A detailed illustration of the effect of decalcification on BC specimens in a real-time manner is lacking in the literature. Herein, we sought to determine the impact of decalcification on the IHC expression pattern of the above listed markers on BC tissue following decalcification. After Institutional Review Board approval, sections from the residual tumor specimens were collected prospectively from 15 BC excision specimens and 1 curetting from a BC bone metastasis. The sections (3 to 6 sections/case) for decalcification were collected following routine submission for pathologic evaluation. The sections were subjected to hydrochloric acid (HCl)-based Decal Stat decalcifying solution for 2, 12, 18, and 24 hours in each case. IHC studies for ER, PR, Ki-67, p53, and Her-2/neu were performed on 1 representative section of the regularly processed tumor block and 1 decalcified tumor block from each time point. Scoring of ER and PR were performed according to the Allred scoring system. Scoring of Her-2/neu was performed according to CAP/ASCO guidelines. The

  7. ErbB2-enhanced invasiveness of H-Ras MCF10A breast cells requires MMP-13 and uPA upregulation via p38 MAPK signaling.

    Science.gov (United States)

    Yong, Hae-Young; Kim, In-Young; Kim, Jong Suk; Moon, Aree

    2010-02-01

    Overexpression of ErbB2 has been frequently found in mammary carcinoma. We have previously shown that the aberrant activation of H-Ras induces human breast cell invasion and migration. The present study was aimed at investigating the effect of ErbB2 overexpression on H-Ras-induced breast cell invasion and to elucidate the underlying mechanisms. Herein, we show that overexpression of ErbB2 promotes invasive and migratory abilities of H-Ras-activated MCF10A human breast epithelial cells through upregulation of matrix metalloproteinase (MMP)-13 and urokinase-type plasminogen activator (uPA). We also demonstrate that the p38 MAPK is an important signaling molecule in the ErbB2-induced upregulation of MMP-13 and uPA and invasion/migration of H-Ras MCF10A cells overexpressing ErbB2. The present study elucidating the molecular mechanism underlying ErbB2-induced promotion of H-Ras MCF10A cell invasion may provide invaluable information for understanding breast cancer progression and establishing therapeutic interventions for breast cancer.

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

    Science.gov (United States)

    2017-09-25

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

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

    Science.gov (United States)

    2011-12-07

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

  10. Matrix-assisted laser desorption/ionization mass spectrometry imaging of cell cultures for the lipidomic analysis of potential lipid markers in human breast cancer invasion.

    Science.gov (United States)

    Wang, Shujuan; Chen, Xiaowu; Luan, Hemi; Gao, Dan; Lin, Shuhai; Cai, Zongwei; Liu, Jianjun; Liu, Hongxia; Jiang, Yuyang

    2016-02-28

    Breast cancer is the leading cause of cancer death among women worldwide. Identification of lipid targets that play a role in breast cancer invasion may advance our understanding of the rapid progression of cancer and may lead to the development of new biomarkers for the disease. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) was applied for the lipidomic profiling of two poorly invasive and two highly invasive breast cancer cell lines to identify the differentially accumulated lipids related to the invasive phenotype. The four cell lines were individually grown on indium tin oxide (ITO)-coated glass slides, analyzed as cell cultures. The raster width and matrix for detection were optimized to improve detection sensitivity. Optimized MSI measurements were performed directly on the cell culture with 9-aminoacridine as matrix, resulting in 215 endogenous compounds detected in positive ion mode and 267 endogenous compounds in negative ion mode in all the four cell lines, representing the largest group of analytes that have been analyzed from cells by a single MSI study. In highly invasive cell lines, 31 lipids including phosphatidylglycerol (PG) and phosphatidic acids were found upregulated and eight lipids including sphingomyelin (SM) downregulated in negative ion mode. The products of de novo fatty acid synthesis incorporated into membrane phospholipids, like oleic-acid-containing PG, may be involved in mitochondrial dysfunction and thus affect the invasion of breast cancer cells. The deficiency of SM may be related to the disruption of apoptosis in highly invasive cancer cells. This work uncovered more analytes in cells by MSI than previous reports, providing a better visualization and novel insights to advance our understanding of the relationship between rapid progression of breast cancer and lipid metabolism. The most altered lipids may aid the discovery of diagnostic markers and therapeutic targets of breast cancer. Copyright

  11. Prostate-Derived Ets Transcription Factor Overexpression is Associated with Nodal Metastasis, Hormone Receptor Positivity in Invasive Breast Cancer

    Directory of Open Access Journals (Sweden)

    Simon Turcotte

    2007-10-01

    Full Text Available Prostate-derived Ets transcription factor (PDEF has recently been associated with invasive breast cancer, but no expression profile has been defined in clinical specimens. We undertook a comprehensive PDEF transcriptional expression study of 86 breast cancer clinical specimens, several cell lines, normal tissues. PDEF expression profile was analyzed according to standard clinicopathologic parameters, compared with hormonal receptor, HER-2/neu status, to the expression of the new tumor biomarker Dikkopf-1 (DKK1. Wide ranging PDEF overexpression was observed in 74% of tested tumors, at higher levels than the average expression found in normal breasts. High PDEF expression was associated with hormone receptor positivity (P < .001, moderate to good differentiation (less than grade III, P = .01, dissemination to axillary lymph nodes (P = .002. PDEF was an independent risk factor for nodal involvement (multivariate analysis, odds ratio 1.250, P = .002. It was expressed in a different subgroup compared to DKK1-expressing tumors (P < .001. Our data imply that PDEF mRNA expression could be useful in breast cancer molecular staging. Further insights into PDEF functions at the protein level, possible links with hormone receptors biology, bear great potential for new therapeutic avenues.

  12. The exon 38-containing ARHGEF11 splice isoform is differentially expressed and is required for migration and growth in invasive breast cancer cells.

    Science.gov (United States)

    Itoh, Masahiko; Radisky, Derek C; Hashiguchi, Masaaki; Sugimoto, Hiroyuki

    2017-11-03

    Breast cancer invasion involves the loss of cell-cell junctions and acquisition of an invasive, migratory phenotype, and breast cancer cells of the basal intrinsic subtype are more invasive and metastatic than breast cancer cells of other subtypes. ARHGEF11 is a RhoGEF that was previously shown to bind to the tight junction protein ZO-1 at perijunctional actomyosin ring (PJAR), a network of cortically organized actin and myosin filaments associated with junctional complexes that regulates cell-cell adhesion and polarization. We show here that ARHGEF11 shows splice isoform expression that differs according to the intrinsic subtype of breast cancer cells and that controls their invasive phenotype. Luminal subtype breast cancer cells express the isoform of ARHGEF11 lacking exon 38 (38-), which binds to ZO-1 at PJAR and is necessary for formation and maintenance of cell-cell junctions. Basal subtype breast cancer cells express the isoform of ARHGEF11 containing exon 38 (38+), which does not bind to ZO-1 and which drives cell migration and motility. Depletion of ARHGEF11 in basal subtype breast cancer cells is sufficient to alter cell morphology from a mesenchymal stellate form with extensive cell protrusions to a cobblestone-like epithelial form, and to suppress growth and survival both in vitro and in vivo . These findings show that the expression of the particular splice isoform of ARHGEF11 is critically linked to the malignant phenotype of breast cancer cells, identifying ARHGEF11 exon 38(+) as a biomarker and target for therapy of breast cancer.

  13. 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.

  14. Hypofractionated Radiation Therapy in Treating Patients With Stage 0-IIB Breast Cancer

    Science.gov (United States)

    2017-12-05

    Ductal Breast Carcinoma In Situ; Invasive Breast Carcinoma; Stage 0 Breast Cancer; Stage I Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer

  15. Polyphenol-rich strawberry extract (PRSE) shows in vitro and in vivo biological activity against invasive breast cancer cells

    OpenAIRE

    Amatori, Stefano; Mazzoni, Luca; Alvarez-Suarez, Jos? Miguel; Giampieri, Francesca; Gasparrini, Massimiliano; Forbes-Hernandez, Tamara Yuliett; Afrin, Sadia; Errico Provenzano, Alfredo; Persico, Giuseppe; Mezzetti, Bruno; Amici, Augusto; Fanelli, Mirco; Battino, Maurizio

    2016-01-01

    We describe the biological effects of a polyphenol-rich strawberry extract (PRSE), obtained from the ?Alba? variety, on the highly aggressive and invasive basal-like breast cancer cell line A17. Dose-response and time-course experiments showed that PRSE is able to decrease the cellular viability of A17 cells in a time- and dose-dependent manner. PRSE effect on cell survival was investigated in other tumor and normal cell lines of both mouse and human origin, demonstrating that PRSE is more ac...

  16. Expression of TNF-superfamily members BAFF and APRIL in breast cancer: Immunohistochemical study in 52 invasive ductal breast carcinomas

    Directory of Open Access Journals (Sweden)

    Stathopoulos Efstathios N

    2008-03-01

    Full Text Available Abstract Background Recent studies suggest an association between chronic inflammation, modulating the tissue microenvironment, and tumor biology. Tumor environment consists of tumor, stromal and endothelial cells and infiltrating macrophages, T lymphocytes, and dendritic cells, producing an array of cytokines, chemokines and growth factors, accounting for a complex cell interaction and regulation of differentiation, activation, function and survival of tumor and surrounding cells, responsible for tumor progression and spreading or induction of antitumor immune responses and rejection. Tumor Necrosis Factor (TNF family members (19 ligands and 29 receptors represent a pleiotropic family of agents, related to a plethora of cellular events from proliferation and differentiation to apoptosis and tumor reduction. Among these members, BAFF and APRIL (CD257 and CD256 respectively gained an increased interest, in view of their role in cell protection, differentiation and growth, in a number of lymphocyte, epithelial and mesenchymal structures. Methods We have assayed by immunohistochemistry 52 human breast cancer biopsies for the expression of BAFF and APRIL and correlated our findings with clinicopathological data and the evolution of the disease. Results BAFF was ubiquitely expressed in breast carcinoma cells, DCIS, normal-appearing glands and ducts and peritumoral adipocytes. In contrast, APRIL immunoreactive expression was higher in non-malignant as compared to malignant breast structures. APRIL but not BAFF immunoreactivity was higher in N+ tumors, and was inversely related with the grade of the tumors. Neither parameter was related to DFS or the OS of patients. Conclusion Our data show, for the first time, an autocrine secretion of BAFF and APRIL from breast cancer cells, offering new perspectives for their role in neoplastic and normal breast cell biology and offering new perspectives for possible selective intervention in breast cancer.

  17. Use of RNA interference to inhibit integrin (alpha6beta4)-mediated invasion and migration of breast carcinoma cells.

    Science.gov (United States)

    Lipscomb, Elizabeth A; Dugan, Aisling S; Rabinovitz, Isaac; Mercurio, Arthur M

    2003-01-01

    The application of small interfering RNA (siRNA) oligonucleotides to silence gene expression has profound implications for the intervention of human diseases including cancer. Using this technique, we explored the possibility that the alpha6beta4 integrin, a laminin adhesion receptor with a recognized role in the invasive phenotype of many carcinomas, represents a potential therapeutic target to inhibit the migration and invasion of carcinoma cells. We found that siRNA oligonucleotides targeted to either subunit of the alpha6beta4 integrin reduced cell surface expression of this integrin and resulted in decreased invasion of MDA-MB-231 breast carcinoma cells. Interestingly, reduced alpha6beta4 expression also promoted decreased migration on non-laminin substrata indicating that this integrin can function in a ligand-independent manner. In addition, the absence of beta4 expression in these cells augmented the formation of alpha6beta1 heterodimers and increased adhesion to laminin-1. Taken together, these results substantiate the importance of the alpha6beta4 integrin in invasion and migration that has been demonstrated previously by expression of the beta4 subunit in beta4-deficient cell lines and by function blocking antibodies. Furthermore, these data suggest that the utilization of siRNA oligonucleotides to reduce the expression of the alpha6beta4 integrin may be a useful approach to prevent carcinoma cell progression.

  18. 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

  19. PD-L1 expression and the immune microenvironment in primary invasive lobular carcinomas of the breast.

    Science.gov (United States)

    Thompson, Elizabeth D; Taube, Janis M; Asch-Kendrick, Rebecca J; Ogurtsova, Aleksandra; Xu, Haiying; Sharma, Rajni; Meeker, Alan; Argani, Pedram; Emens, Leisha A; Cimino-Mathews, Ashley

    2017-11-01

    Tumor-infiltrating lymphocytes and immune checkpoint proteins such as PD-L1 are potential prognostic factors and therapeutic targets in breast cancer. Most studies characterizing the breast tumor immune microenvironment have focused on ductal carcinomas. Here we investigate the tumor microenvironment of primary invasive lobular carcinomas. Previously constructed tissue microarrays of 47 lobular carcinomas were labeled by immunohistochemistry for PD-L1, CD8, CD20, and FoxP3. The stromal immune infiltrate density was qualitatively scored as a percentage of tumor area: 1+ (50%). The average immune cell subtype per high-power field was quantitatively scored. The percentage PD-L1 labeling on tumor-infiltrating lymphocytes was scored as none, focal (lobular carcinomas contained PD-L1 + tumor-infiltrating lymphocytes with the majority showing 1+ immune infiltrates with focal-moderate PD-L1 labeling. PD-L1 was expressed by tumor cells in 17% of lobular carcinomas. In contrast to ductal carcinomas, there was no correlation between the immune infiltrate density, the PD-L1 expression by lobular carcinoma cells, tumor grade, or the expression of estrogen receptor or human epidermal growth factor receptor-2. However, both the tumor-infiltrating lymphocyte density and the average CD8 + T-cell counts correlated with immune cell PD-L1 status (P=0.004 and 0.03, respectively). Similar to breast ductal carcinomas, PD-L1 + lobular breast carcinomas had higher numbers of PD-L1 + tumor-infiltrating lymphocytes (63%) than PD-L1 - lobular carcinomas (23%; P=0.04). These data show that a subset of primary breast lobular carcinomas both express PD-L1 on tumor cells and contain PD-L1 + tumor-infiltrating lymphocytes, suggesting the possibility of both constitutive and adaptive PD-L1 expression. Together, these results support immunotherapy as a potential treatment for a subset of patients with primary invasive lobular breast carcinomas.

  20. The diagnosis and management of pre-invasive breast disease: Problems associated with management of pre-invasive lesions

    International Nuclear Information System (INIS)

    Purushotham, Anand D

    2003-01-01

    The treatment of ductal carcinoma in situ (DCIS) involves adequate surgical excision with adjuvant radiotherapy where appropriate. An inadequate excision margin and young age are independent risk factors for local recurrence. Routine surgery to axillary lymph nodes is not recommended in pure DCIS. In localised DCIS, adjuvant radiotherapy is recommended on the basis of tumour size, margin width and pathological subtypes. The role of adjuvant tamoxifen as systemic therapy is controversial. The treatment of atypical ductal/lobular hyperplasia and lobular carcinoma in situ involves surgical excision to exclude coexisting DCIS or invasive disease

  1. p130Cas substrate domain signaling promotes migration, invasion, and survival of estrogen receptor-negative breast cancer cells

    Directory of Open Access Journals (Sweden)

    Anna C Cunningham-Edmondson

    2009-12-01

    Full Text Available Anna C Cunningham-Edmondson1,2, Steven K Hanks11Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN, USA; 2Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta, GA, USAAbstract: Elevated Src tyrosine kinase activity is commonly observed in breast cancer and likely contributes to neoplasia and malignancy. p130Cas (“Crk-associated substrate” is a major Src substrate found at the sites where integrins mediate cell adhesion to the extracellular matrix. Src phosphorylates multiple tyrosines in the p130Cas “substrate domain” (SD and this signaling event has been implicated in the promotion of cell motility, primarily from studies on fibroblasts. In breast cancer, studies on p130Cas have focused on its role in conferring antiestrogen resistance to cells that express the estrogen receptor (ER+. However, little is known regarding the role of p130Cas in the more aggressive estrogen receptor negative (ER- breast cancers for which there is a need for development of effective targeted therapies. We found high levels of p130Cas SD tyrosine phosphorylation to be a common characteristic of ER- breast cancer cell lines, with particularly high levels observed for the BT-549 cell line. Using RNA interference to knock down p130Cas expression in BT-549 cells, combined with rescue by WT p130Cas versus a signaling-deficient control, we provide evidence that p130Cas SD tyrosine phosphorylation is an important signaling event in the migration, invasion, proliferation, and survival of this ER- breast cancer cell line.Keywords: adhesion, BCAR1, integrins, Src, FAK, tyrosine phosphorylation

  2. Loss of cadherin-based cell adhesion and the progression of Invasive Lobular Breast Cancer

    NARCIS (Netherlands)

    Vlug, E.J.

    2015-01-01

    Lobular breast cancer is a type of breast cancer that is histologically characterized by a noncohesive growth pattern of small regular cells, where single cells infiltrate as one-layered strands of cells. This noncohesive growth pattern is due to inactivation of the E-cadherin complex and a

  3. Comparative genomic hybridization analysis of benign and invasive male breast neoplasms

    DEFF Research Database (Denmark)

    Ojopi, Elida Paula Benquique; Cavalli, Luciane Regina; Cavalieri, Luciane Mara Bogline

    2002-01-01

    Comparative genomic hybridization (CGH) analysis was performed for the identification of chromosomal imbalances in two benign gynecomastias and one malignant breast carcinoma derived from patients with male breast disease and compared with cytogenetic analysis in two of the three cases. CGH analy...

  4. The nude mouse as an in vivo model for human breast cancer invasion and metastasis

    DEFF Research Database (Denmark)

    Brünner, N; Boysen, B; Rømer, J

    1993-01-01

    Human breast cancer xenografts only rarely invade and metastasize in nude mice, and have therefore only had limited use as a model for studying mechanisms involved in breast cancer spreading. However, recent reports describe differences not only between various cell lines but also between strains...

  5. Comparison of Visual and automated assessment of Ki-67 proliferative activity and their impact on outcome in primary operable invasive ductal breast cancer

    OpenAIRE

    Mohammed, Z M A; McMillan, D C; Elsberger, B; Going, J J; Orange, C; Mallon, E; Doughty, J C; Edwards, J

    2012-01-01

    Background: Immunohistochemistry of Ki-67 protein is widely used to assess tumour proliferation, and is an established prognostic factor in breast cancer. There is interest in automating the assessment of Ki-67 labelling index (LI) with possible benefits in handling increased workload, with improved accuracy and precision. Patients and methods: Visual and automated assessment of Ki-67 LI and survival were examined in patients with primary operable invasive ductal breast cancer. Tissue microar...

  6. Targeting Alpha5 Beta1 Integrin to Prevent Metastatic Breast Cancer Cell Invasion: PhScN Target Site Definition and Plasma Stability

    Science.gov (United States)

    2015-11-01

    phosphatidylinositol 3’-kinase and its downstream signals in erbB-2- mediated transformation . Mol Cancer Res, 2003. 1(7): p. 551-60. PMID: 12754302 16. Aota S, Nomizu M... mediated invasion through noncovalent interaction with α5β1 receptors of SUM149PT and MDA-MB-231 metastatic human breast cancer cells, and laid the...foundation for detailed structure–activity relationship (SAR) studies for both peptides as inhibitors of α5β1– mediated metastatic breast cancer invasion

  7. Strong adverse effect of epidermal growth factor receptor 2 overexpression on prognosis of patients with invasive lobular breast cancer: a comparative study with invasive ductal breast cancer in Chinese population.

    Science.gov (United States)

    Wang, Tong; Ma, Yuanyuan; Wang, Liang; Liu, Hong; Chen, Meixuan; Niu, Ruifang

    2015-08-01

    The data on the outcome of breast invasive lobular carcinoma (ILC) are conflicting. In addition, the prognostic effect of molecular subtypes on ILC remains unclear. In this study, the clinicopathological and prognostic data between 269 ILC and 816 invasive ductal carcinoma (IDC) cases in a Chinese population were extensively compared, with a median follow-up time of 7.8 years. Compared with the IDC group, ILC tumors had more lymph node invasion, hormonal receptor positivity, and human epidermal growth factor receptor 2 (HER2) negativity. ILC patients showed overall survival (OS) and recurrence/metastasis-free survival (RFS) rates similar to those of IDC patients but exhibited worse disease-free survival (DFS) rate because of the higher rate of contralateral breast cancer (BC). Further analysis showed that OS, RFS, and DFS were similar between ILC and IDC patients in the subgroups of luminal A and triple-negative BC with HER2 negativity but were worse in ILC patients than those in IDC patients in the subgroups of luminal B and HER2 overexpression with positive HER2 expression. Multivariate analysis indicated HER2 positivity as an independent risk factor for OS, RFS, and DFS of ILC patients, which increased the risk in the ILC group than that in IDC group. The interaction of HER2 and ILC was also defined as an independent risk factor for OS, RFS, and DFS of the entire population. In conclusion, overexpression of HER2 exhibited stronger negative effect on the prognosis of ILC patients than that in IDC patients, suggesting that treatment targeting HER2 is crucial for this BC subgroup.

  8. Integration of genomic, transcriptomic and proteomic data identifies two biologically distinct subtypes of invasive lobular breast cancer.

    Science.gov (United States)

    Michaut, Magali; Chin, Suet-Feung; Majewski, Ian; Severson, Tesa M; Bismeijer, Tycho; de Koning, Leanne; Peeters, Justine K; Schouten, Philip C; Rueda, Oscar M; Bosma, Astrid J; Tarrant, Finbarr; Fan, Yue; He, Beilei; Xue, Zheng; Mittempergher, Lorenza; Kluin, Roelof J C; Heijmans, Jeroen; Snel, Mireille; Pereira, Bernard; Schlicker, Andreas; Provenzano, Elena; Ali, Hamid Raza; Gaber, Alexander; O'Hurley, Gillian; Lehn, Sophie; Muris, Jettie J F; Wesseling, Jelle; Kay, Elaine; Sammut, Stephen John; Bardwell, Helen A; Barbet, Aurélie S; Bard, Floriane; Lecerf, Caroline; O'Connor, Darran P; Vis, Daniël J; Benes, Cyril H; McDermott, Ultan; Garnett, Mathew J; Simon, Iris M; Jirström, Karin; Dubois, Thierry; Linn, Sabine C; Gallagher, William M; Wessels, Lodewyk F A; Caldas, Carlos; Bernards, Rene

    2016-01-05

    Invasive lobular carcinoma (ILC) is the second most frequently occurring histological breast cancer subtype after invasive ductal carcinoma (IDC), accounting for around 10% of all breast cancers. The molecular processes that drive the development of ILC are still largely unknown. We have performed a comprehensive genomic, transcriptomic and proteomic analysis of a large ILC patient cohort and present here an integrated molecular portrait of ILC. Mutations in CDH1 and in the PI3K pathway are the most frequent molecular alterations in ILC. We identified two main subtypes of ILCs: (i) an immune related subtype with mRNA up-regulation of PD-L1, PD-1 and CTLA-4 and greater sensitivity to DNA-damaging agents in representative cell line models; (ii) a hormone related subtype, associated with Epithelial to Mesenchymal Transition (EMT), and gain of chromosomes 1q and 8q and loss of chromosome 11q. Using the somatic mutation rate and eIF4B protein level, we identified three groups with different clinical outcomes, including a group with extremely good prognosis. We provide a comprehensive overview of the molecular alterations driving ILC and have explored links with therapy response. This molecular characterization may help to tailor treatment of ILC through the application of specific targeted, chemo- and/or immune-therapies.

  9. Modeling invasive lobular breast carcinoma by CRISPR/Cas9-mediated somatic genome editing of the mammary gland.

    Science.gov (United States)

    Annunziato, Stefano; Kas, Sjors M; Nethe, Micha; Yücel, Hatice; Del Bravo, Jessica; Pritchard, Colin; Bin Ali, Rahmen; van Gerwen, Bas; Siteur, Bjørn; Drenth, Anne Paulien; Schut, Eva; van de Ven, Marieke; Boelens, Mirjam C; Klarenbeek, Sjoerd; Huijbers, Ivo J; van Miltenburg, Martine H; Jonkers, Jos

    2016-06-15

    Large-scale sequencing studies are rapidly identifying putative oncogenic mutations in human tumors. However, discrimination between passenger and driver events in tumorigenesis remains challenging and requires in vivo validation studies in reliable animal models of human cancer. In this study, we describe a novel strategy for in vivo validation of candidate tumor suppressors implicated in invasive lobular breast carcinoma (ILC), which is hallmarked by loss of the cell-cell adhesion molecule E-cadherin. We describe an approach to model ILC by intraductal injection of lentiviral vectors encoding Cre recombinase, the CRISPR/Cas9 system, or both in female mice carrying conditional alleles of the Cdh1 gene, encoding for E-cadherin. Using this approach, we were able to target ILC-initiating cells and induce specific gene disruption of Pten by CRISPR/Cas9-mediated somatic gene editing. Whereas intraductal injection of Cas9-encoding lentiviruses induced Cas9-specific immune responses and development of tumors that did not resemble ILC, lentiviral delivery of a Pten targeting single-guide RNA (sgRNA) in mice with mammary gland-specific loss of E-cadherin and expression of Cas9 efficiently induced ILC development. This versatile platform can be used for rapid in vivo testing of putative tumor suppressor genes implicated in ILC, providing new opportunities for modeling invasive lobular breast carcinoma in mice. © 2016 Annunziato et al.; Published by Cold Spring Harbor Laboratory Press.

  10. Breast cancer cells induce stromal fibroblasts to secrete ADAMTS1 for cancer invasion through an epigenetic change.

    Directory of Open Access Journals (Sweden)

    Shiaw-Wei Tyan

    Full Text Available Microenvironment plays an important role in cancer development. We have reported that the cancer-associated stromal cells exhibit phenotypic and functional changes compared to stromal cells neighboring to normal tissues. However, the molecular mechanisms as well as the maintenance of these changes remain elusive. Here we showed that through co-culture with breast cancer cells for at least three to four passages, breast normal tissue-associated fibroblasts (NAFs gained persistent activity for promoting cancer cell invasion, partly via up-regulating ADAM metallopeptidase with thrombospondin type 1 motif, 1 (ADAMTS1. Furthermore, we demonstrated that the DNA methylation pattern in the ADAMTS1 promoter has no alteration. Instead, the loss of EZH2 binding to the ADAMTS1 promoter and the resulting decrease of promoter-associated histone H3K27 methylation may account for the up-regulation of ADAMTS1. Importantly, the lack of EZH2 binding and the H3K27 methylation on the ADAMTS1 promoter were sustained in cancer cell-precocultured NAFs after removal of cancer cells. These results suggest that cancer cells are capable of inducing stromal fibroblasts to secrete ADAMTS1 persistently for their invasion and the effect is epigenetically inheritable.

  11. Progestin Stimulation of Manganese Superoxide Dismutase and Invasive Properties in T47D Human Breast Cancer Cells

    Science.gov (United States)

    Holley, Aaron K.; Kiningham, Kelley K.; Spitz, Douglas R.; Edwards, Dean P.; Jenkins, Jeffrey T.; Moore, Michael R.

    2009-01-01

    Superoxide Dismutase (SOD) occurs in two intracellular forms in mammals, copper-zinc SOD (CuZnSOD), found in the cytoplasm, mitochondria and nucleus, and manganese superoxide dismutase (MnSOD), in mitochondria. Changes in MnSOD expression (as compared to normal cells) have been reported in several forms of cancer, and these changes have been associated with regulation of cell proliferation, cell death, and metastasis. We have found that progestins stimulate MnSOD in T47D human breast cancer cells in a time and physiological concentration-dependent manner, exhibiting specificity for progestins and inhibition by the antiprogestin RU486. Progestin stimulation occurs at the level of mRNA, protein, and enzyme activity. Cycloheximide inhibits stimulation at the mRNA level, suggesting that progestin induction of MnSOD mRNA depends on synthesis of protein. Experiments with the MEK inhibitor UO126 suggest involvement of the MAP kinase signal transduction pathway. Finally, MnSOD-directed siRNA lowers progestin-stimulated MnSOD and inhibits progestin stimulation of migration and invasion, suggesting that up-regulation of MnSOD may be involved in the mechanism of progestin stimulation of invasive properties. To our knowledge, this is the first characterization of progestin stimulation of MnSOD in human breast cancer cells . PMID:19563893

  12. Modeling invasive lobular breast carcinoma by CRISPR/Cas9-mediated somatic genome editing of the mammary gland

    Science.gov (United States)

    Annunziato, Stefano; Kas, Sjors M.; Nethe, Micha; Yücel, Hatice; Del Bravo, Jessica; Pritchard, Colin; Bin Ali, Rahmen; van Gerwen, Bas; Siteur, Bjørn; Drenth, Anne Paulien; Schut, Eva; van de Ven, Marieke; Boelens, Mirjam C.; Klarenbeek, Sjoerd; Huijbers, Ivo J.; van Miltenburg, Martine H.; Jonkers, Jos

    2016-01-01

    Large-scale sequencing studies are rapidly identifying putative oncogenic mutations in human tumors. However, discrimination between passenger and driver events in tumorigenesis remains challenging and requires in vivo validation studies in reliable animal models of human cancer. In this study, we describe a novel strategy for in vivo validation of candidate tumor suppressors implicated in invasive lobular breast carcinoma (ILC), which is hallmarked by loss of the cell–cell adhesion molecule E-cadherin. We describe an approach to model ILC by intraductal injection of lentiviral vectors encoding Cre recombinase, the CRISPR/Cas9 system, or both in female mice carrying conditional alleles of the Cdh1 gene, encoding for E-cadherin. Using this approach, we were able to target ILC-initiating cells and induce specific gene disruption of Pten by CRISPR/Cas9-mediated somatic gene editing. Whereas intraductal injection of Cas9-encoding lentiviruses induced Cas9-specific immune responses and development of tumors that did not resemble ILC, lentiviral delivery of a Pten targeting single-guide RNA (sgRNA) in mice with mammary gland-specific loss of E-cadherin and expression of Cas9 efficiently induced ILC development. This versatile platform can be used for rapid in vivo testing of putative tumor suppressor genes implicated in ILC, providing new opportunities for modeling invasive lobular breast carcinoma in mice. PMID:27340177

  13. Targeting Epirubicin Plus Quinacrine Liposomes Modified with DSPE-PEG2000-C(RGDfK) Conjugate for Eliminating Invasive Breast Cancer.

    Science.gov (United States)

    Sun, Meng-Ge; Shi, Ji-Feng; Li, Xiu-Ying; Zhao, Yao; Ju, Rui-Jun; Mu, Li-Min; Yan, Yan; Li, Xue-Tao; Zeng, Fan; Lu, Wan-Liang

    2015-08-01

    Recurrence of invasive breast cancer could arise from the residual cancer cells after comprehensive treatment. It is possible that residual invasive cancer cells are capable of forming highly patterned vasculogenic mimicry (VM) channels, leading to relapse and metastasis. In the present study, a new type of targeting epirubicin plus quinacrine liposomes was developed by modifying functional DSPE-PEG2000 with C(RGDfK), a cyclic peptide containing Arg-Gly-Asp. These liposomes could potentially eliminate invasive breast cancer and destroy VM channels. Evaluations were made in human invasive breast cancer cells and their xenografts in nude mice. The results showed that the targeting epirubicin plus quinacrine liposomes could enhance the accumulation and uptake of the drugs in cancer tissues, kill cancer cells directly, activate apoptotic enzymes, destroy the VM channels and downregulate the VM channel-forming marker molecules (EphA2, FAK, PI3K, MMP 9, MMP 14, VE-Cad and HIF-α), thereby exhibiting a strong overall anticancer efficacy. The targeting epirubicin plus quinacrine liposomes provided a promising strategy to treat invasive breast cancer and to prevent the relapse arising from VM channels after chemotherapy.

  14. Retrospective evaluation of histopathological examinations in invasive ductal breast cancer of no special type: an analysis of 691 patients.

    Science.gov (United States)

    Badowska-Kozakiewicz, Anna M; Liszcz, Anna; Sobol, Maria; Patera, Janusz

    2017-10-01

    Invasive ductal carcinoma (IDC) is the most common type of breast cancer in women and accounts for about 80% of all breast cancers. The material consisted of histological preparations derived from 691 patients treated for IDC-NST. In our own study material, invasive ductal breast cancer of no special type accounted for more than 60% of cases, with the largest percentage of tumors being classified as G2 (53.96%) and G3 (28.98%). In terms of tumor size, the most common IDC-NST tumors were those of stage T1c (34.59%) and T2 (35.31%). The incidence of lymph node involvement was also assessed to reveal that no lymph node metastases were present in 45.44% of IDC-NST tumors. In the histopathological analysis of IDC-NST, significant statistical correlation was demonstrated between the presence of lymph node metastases and the histological malignancy grade (N0/G1-G3 p = 0.0103; N1A/G1-G3 p = 0.0498; N1B/G1-G3 p < 0.001; N3/G1-G3 p = 0.0027; N4/G1-G3 p < 0.001), between the presence of lymph node metastases and the tumor size (N0/T1-T4 p = 0.00295; N1B/T1-T4 p < 0.001; N2/T1-T4 p < 0.001; N2A/T1-T2 p < 0.001; N4/T1-T4 p < 0.001; Nx/T1-T4 p = 0.0447), as well as between the histological malignancy grade and the tumor size (G1/T1-T4 p < 0.001; G1/2/T1-T4 p < 0.001; G2/3/T1-T4 p < 0.0267). Own research demonstrated that the most common histological type of breast cancer is invasive ductal carcinoma of no special type (IDC-NST); statistically significant correlations were demonstrated in IDC-NST patients between the lymph node involvement status and the histological malignancy grade or tumor size as well as between the histological malignancy grade and the tumor size.

  15. Non-invasive optical estimate of tissue composition to differentiate malignant from benign breast lesions: A pilot study

    Science.gov (United States)

    Taroni, Paola; Paganoni, Anna Maria; Ieva, Francesca; Pifferi, Antonio; Quarto, Giovanna; Abbate, Francesca; Cassano, Enrico; Cubeddu, Rinaldo

    2017-01-01

    Several techniques are being investigated as a complement to screening mammography, to reduce its false-positive rate, but results are still insufficient to draw conclusions. This initial study explores time domain diffuse optical imaging as an adjunct method to classify non-invasively malignant vs benign breast lesions. We estimated differences in tissue composition (oxy- and deoxyhemoglobin, lipid, water, collagen) and absorption properties between lesion and average healthy tissue in the same breast applying a perturbative approach to optical images collected at 7 red-near infrared wavelengths (635-1060 nm) from subjects bearing breast lesions. The Discrete AdaBoost procedure, a machine-learning algorithm, was then exploited to classify lesions based on optically derived information (either tissue composition or absorption) and risk factors obtained from patient’s anamnesis (age, body mass index, familiarity, parity, use of oral contraceptives, and use of Tamoxifen). Collagen content, in particular, turned out to be the most important parameter for discrimination. Based on the initial results of this study the proposed method deserves further investigation.

  16. MRI kinetics with volumetric analysis in correlation with hormonal receptor subtypes and histologic grade of invasive breast cancers.

    Science.gov (United States)

    Leong, Lester Chee Hao; Gombos, Eva C; Jagadeesan, Jayender; Fook-Chong, Stephanie Man Chung

    2015-03-01

    OBJECTIVE. The aim of this study was to assess whether computer-assisted detection-processed MRI kinetics data can provide further information on the biologic aggressiveness of breast tumors. MATERIALS AND METHODS. We identified 194 newly diagnosed invasive breast cancers presenting as masses on contrast-enhanced MRI by a HIPAA-compliant pathology database search. Computer-assisted detection-derived data for the mean and median peak signal intensity percentage increase, most suspicious kinetic curve patterns, and volumetric analysis of the different kinetic patterns by mean percentage tumor volume were compared against the different hormonal receptor (estrogen-receptor [ER], progesterone-receptor [PR], ERRB2 (HER2/neu), and triple-receptor expressivity) and histologic grade subgroups, which were used as indicators of tumor aggressiveness. RESULTS. The means and medians of the peak signal intensity percentage increase were higher in ER-negative, PR-negative, and triple-negative (all p ≤ 0.001), and grade 3 tumors (p = 0.011). Volumetric analysis showed higher mean percentage volume of rapid initial enhancement in biologically more aggressive ER-negative, PR-negative, and triple-negative tumors compared with ER-positive (64% vs 53.6%, p = 0.013), PR-positive (65.4% vs 52.5%, p = 0.001), and nontriple-negative tumors (65.3% vs 54.6%, p = 0.028), respectively. A higher mean percentage volume of rapid washout component was seen in ERRB2-positive tumors compared with ERRB2-negative tumors (27.5% vs 17.9%, p = 0.020). CONCLUSION. Peak signal intensity percentage increase and volume analysis of the different kinetic patterns of breast tumors showed correlation with hormonal receptor and histologic grade indicators of cancer aggressiveness. Computer-assisted detection-derived MRI kinetics data have the potential to further characterize the aggressiveness of an invasive cancer.

  17. Bilateral invasive lobular breast cancer in a female teenager: a rare finding of a common disease - case report and review of literature

    Directory of Open Access Journals (Sweden)

    Ndumbe Peter

    2010-07-01

    Full Text Available Management of cancer patients in low-resource communities presents enormous challenges. Breast cancer is a public health problem in Cameroon and occurs mostly in elderly women. The predominant histological type is a duct carcinoma. Lobular carcinoma in teenagers is rare. In this report we present a case of bilateral invasive lobular carcinoma of the breast that was confirmed on biopsies in a 22-year-old female. We present this rare finding and review the pathological, clinical and radiographic challenges of the disease. Nodules in the breast from patients of any age should be submitted for histology. Public education is beneficial and should be intensified

  18. The Contribution of Risk Factors to the Higher Incidence of Invasive and In Situ Breast Cancers in Women With Higher Levels of Education in the European Prospective Investigation Into Cancer and Nutrition

    NARCIS (Netherlands)

    Menvielle, Gwenn; Kunst, Anton E.; van Gils, Carla H.; Peeters, Petra H.; Boshuizen, Hendriek; Overvad, Kim; Olsen, Anja; Tjonneland, Anne; Hermann, Silke; Kaaks, Rudolf; Bergmann, Manuela M.; Illner, Anne-Kathrin; Lagiou, Pagona; Trichopoulos, Dimitrios; Trichopoulou, Antonia; Palli, Domenico; Berrino, Franco; Mattiello, Amelia; Tumino, Rosario; Sacerdote, Carlotta; May, Anne; Monninkhof, Evelyn; Braaten, Tonje; Lund, Eiliv; Ramon Quiros, Jose; Duell, Eric J.; Sanchez, Maria-Jose; Navarro, Carmen; Ardanaz, Eva; Borgquist, Signe; Manjer, Jonas; Khaw, Kay Tee; Allen, Naomi E.; Reeves, Gillian K.; Chajes, Veronique; Rinaldi, Sabina; Slimani, Nadia; Gallo, Valentina; Vineis, Paolo; Riboli, Elio; Bueno-de-Mesquita, H. Bas

    2011-01-01

    The authors investigated the role of known risk factors in educational differences in breast cancer incidence. Analyses were based on the European Prospective Investigation Into Cancer and Nutrition and included 242,095 women, 433 cases of in situ breast cancer, and 4,469 cases of invasive breast

  19. The contribution of risk factors to the higher incidence of invasive and in situ breast cancers in women with higher levels of education in the European prospective investigation into cancer and nutrition

    NARCIS (Netherlands)

    Menvielle, Gwenn; Kunst, Anton E.; van Gils, Carla H.; Peeters, Petra H.; Boshuizen, Hendriek; Overvad, Kim; Olsen, Anja; Tjonneland, Anne; Hermann, Silke; Kaaks, Rudolf; Bergmann, Manuela M.; Illner, Anne-Kathrin; Lagiou, Pagona; Trichopoulos, Dimitrios; Trichopoulou, Antonia; Palli, Domenico; Berrino, Franco; Mattiello, Amelia; Tumino, Rosario; Sacerdote, Carlotta; May, Anne; Monninkhof, Evelyn; Braaten, Tonje; Lund, Eiliv; Quirós, José Ramón; Duell, Eric J.; Sánchez, Maria-José; Navarro, Carmen; Ardanaz, Eva; Borgquist, Signe; Manjer, Jonas; Khaw, Kay Tee; Allen, Naomi E.; Reeves, Gillian K.; Chajes, Véronique; Rinaldi, Sabina; Slimani, Nadia; Gallo, Valentina; Vineis, Paolo; Riboli, Elio; Bueno-de-Mesquita, H. Bas

    2011-01-01

    The authors investigated the role of known risk factors in educational differences in breast cancer incidence. Analyses were based on the European Prospective Investigation Into Cancer and Nutrition and included 242,095 women, 433 cases of in situ breast cancer, and 4,469 cases of invasive breast

  20. Axillary fine needle aspiration cytology for pre-operative staging of patients with screen-detected invasive breast carcinoma.

    LENUS (Irish Health Repository)

    Hayes, Brian D

    2012-02-01

    INTRODUCTION: Fine needle aspiration cytology (FNAC) of radiologically abnormal axillary lymph nodes in patients with breast cancer can identify patients suitable for primary axillary clearance (AC) rather than sentinel node biopsy, enabling surgical axillary staging by a single operation. This study assessed the accuracy of FNAC in predicting positive axillary lymph nodes. METHODS: 161 patients with screen-detected invasive carcinoma and who had pre-operative FNAC of a radiologically abnormal axillary lymph node were identified from two screening units, The axillary FNAC reports were correlated with sentinel node biopsy and AC reports, and sensitivity, specificity, positive (PPV) and negative (NPV) predictive values were calculated. RESULTS: FNAC had a moderate sensitivity (66.3%) and NPV (71.8%), and a high specificity (98.7%) and PPV (98.3%). Most patients (86%) had a single axillary operation. The sensitivity was highest in grade 3 (81.8%) and ductal type (77.8%) tumours. The sensitivity was lower in tumours of special type (34.8%), grade 1 tumours (50%) and those without lymphovascular invasion (LVI) (55.9%). The NPV was highest in pT1 (86.7%) and in grade 1 (84.5%) tumours, and lowest (44%) in tumours with LVI. The PPV was 100% in grade 1 and 3 tumours, stage pT2 and pT3 tumours and those without LVI, and was high (>96%) in all other groups. In lymph-node-positive patients, the mean number of lymph nodes involved was higher in the case of a positive (6.4) than negative FNAC (4.4). CONCLUSIONS: FNAC of ultrasonically abnormal axillary lymph nodes achieved surgical staging by a single operation in most patients with screen-detected invasive breast carcinoma, with moderate sensitivity and high specificity.

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

    Directory of Open Access Journals (Sweden)

    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

  2. Lobular histology and response to neoadjuvant chemotherapy in invasive breast cancer

    NARCIS (Netherlands)

    Lips, Esther H.; Mukhtar, Rita A.; Yau, Christina; de Ronde, Jorma J.; Livasy, Chad; Carey, Lisa A.; Loo, Claudette E.; Vrancken-Peeters, Marie-Jeanne T. F. D.; Sonke, Gabe S.; Berry, Donald A.; van't Veer, Laura J.; Esserman, Laura J.; Wesseling, Jelle; Rodenhuis, Sjoerd; Shelley Hwang, E.

    2012-01-01

    Invasive lobular carcinoma (ILC) has been reported to be less responsive to neoadjuvant chemotherapy (NAC) than invasive ductal carcinoma (IDC). We sought to determine whether ILC histology indeed predicts poor response to NAC by analyzing tumor characteristics such as protein expression, gene

  3. Localization of uPAR and MMP-9 in lipid rafts is critical for migration, invasion and angiogenesis in human breast cancer cells

    Directory of Open Access Journals (Sweden)

    Estes Norman

    2010-11-01

    Full Text Available Abstract Background uPAR and MMP-9, which play critical roles in tumor cell invasion, migration and angiogenesis, have been shown to be associated with lipid rafts. Methods To investigate whether cholesterol could regulate uPAR and MMP-9 in breast carcinoma, we used MβCD (methyl beta cyclodextrin, which extracts cholesterol from lipid rafts to disrupt lipid rafts and studied its effect on breast cancer cell migration, invasion, angiogenesis and signaling. Results Morphological evidence showed the association of uPAR with lipid rafts in breast carcinoma cells. MβCD treatment significantly reduced the colocalization of uPAR and MMP-9 with lipid raft markers and also significantly reduced uPAR and MMP-9 at both the protein and mRNA levels. Spheroid migration and invasion assays showed inhibition of breast carcinoma cell migration and invasion after MβCD treatment. In vitro angiogenesis studies showed a significant decrease in the angiogenic potential of cells pretreated with MβCD. MβCD treatment significantly reduced the levels of MMP-9 and uPAR in raft fractions of MDA-MB-231 and ZR 751 cells. Phosphorylated forms of Src, FAK, Cav, Akt and ERK were significantly inhibited upon MβCD treatment. Increased levels of soluble uPAR were observed upon MβCD treatment. Cholesterol supplementation restored uPAR expression to basal levels in breast carcinoma cell lines. Increased colocalization of uPAR with the lysosomal marker LAMP1 was observed in MβCD-treated cells when compared with untreated cells. Conclusion Taken together, our results suggest that cholesterol levels in lipid rafts are critical for the migration, invasion, and angiogenesis of breast carcinoma cells and could be a critical regulatory factor in these cancer cell processes mediated by uPAR and MMP-9.

  4. β-Arrestin2 regulates lysophosphatidic acid-induced human breast tumor cell migration and invasion via Rap1 and IQGAP1.

    Directory of Open Access Journals (Sweden)

    Mistre Alemayehu

    Full Text Available β-Arrestins play critical roles in chemotaxis and cytoskeletal reorganization downstream of several receptor types, including G protein-coupled receptors (GPCRs, which are targets for greater than 50% of all pharmaceuticals. Among them, receptors for lysophosphatidic acid (LPA, namely LPA(1 are overexpressed in breast cancer and promote metastatic spread. We have recently reported that β-arrestin2 regulates LPA(1-mediated breast cancer cell migration and invasion, although the underlying molecular mechanisms are not clearly understood. We show here that LPA induces activity of the small G protein, Rap1 in breast cancer cells in a β-arrestin2-dependent manner, but fails to activate Rap1 in non-malignant mammary epithelial cells. We found that Rap1A mRNA levels are higher in human breast tumors compared to healthy patient samples and Rap1A is robustly expressed in human ductal carcinoma in situ and invasive tumors, in contrast to the normal mammary ducts. Rap1A protein expression is also higher in aggressive breast cancer cells (MDA-MB-231 and Hs578t relative to the weakly invasive MCF-7 cells or non-malignant MCF10A mammary cells. Depletion of Rap1A expression significantly impaired LPA-stimulated migration of breast cancer cells and invasiveness in three-dimensional Matrigel cultures. Furthermore, we found that β-arrestin2 associates with the actin binding protein IQGAP1 in breast cancer cells, and is necessary for the recruitment of IQGAP1 to the leading edge of migratory cells. Depletion of IQGAP1 blocked LPA-stimulated breast cancer cell invasion. Finally, we have identified that LPA enhances the binding of endogenous Rap1A to β-arrestin2, and also stimulates Rap1A and IQGAP1 to associate with LPA(1. Thus our data establish novel roles for Rap1A and IQGAP1 as critical regulators of LPA-induced breast cancer cell migration and invasion.

  5. Breast Cancer Gene Therapy: Development of Novel Non-Invasive Magnetic Resonance Assay to Optimize Efficacy

    National Research Council Canada - National Science Library

    Mason, Ralph P

    2005-01-01

    Gene therapy holds great promise for treatment of breast cancer. In particular; clinical trials are underway to apply therapeutic genes related to pro-drug activation or to modulate the activity of oncogenes by blocking promoter sites...

  6. Breast Cancer Gene Therapy: Development of Novel Non-Invasive Magnetic Resonance Assay to Optimize Efficacy

    National Research Council Canada - National Science Library

    Mason, Ralph

    2004-01-01

    Gene therapy holds great promise for treatment of breast cancer. In particular, clinical trials are underway to apply therapeutic genes related to pro-drug activation or to modulate the activity of oncogenes by blocking promoter sites...

  7. Breast Cancer Gene Therapy: Development of Novel Non-Invasive Magnetic Resonance Assay to Optimize Efficacy

    National Research Council Canada - National Science Library

    Mason, Ralph P

    2007-01-01

    Gene therapy holds great promise for treatment of breast cancer. In particular clinical trials are underway to apply therapeutic genes related to pro-drug activation or to modulate the activity of oncogenes by blocking promoter sites...

  8. Breast Cancer Gene Therapy: Development of Novel Non-Invasive Magnetic Resonance Assay to Optimize Efficacy

    National Research Council Canada - National Science Library

    Mason, Ralph P

    2006-01-01

    Gene therapy holds great promise for treatment of breast cancer. In particular clinical trials are underway to apply therapeutic genes related to pro-drug activation or to modulate the activity of oncogenes by blocking promoter sites...

  9. Association study of prostate cancer susceptibility variants with risks of invasive ovarian, breast, and colorectal cancer

    DEFF Research Database (Denmark)

    Song, H.; Koessler, T.; Ahmed, S.

    2008-01-01

    cancer [per minor allele OR, 1.19; 95% confidence interval (95% CI), 1.04-1.37; P(trend) = 0.012]. This association was stronger for the serous histologic subtype (OR, 1.29; 95% CI, 1.09-1.53; P = 0.003). SNP rs7931342 (chromosome 11q13) showed some evidence of association with breast cancer (per minor...... ovarian, colorectal, and breast cancer. Twelve prostate cancer-associated tag SNPs were genotyped in ovarian (2,087 cases/3,491 controls), colorectal (2,148 cases/2,265 controls) and breast (first set, 4,339 cases/4,552 controls; second set, 3,800 cases/3,995 controls) case-control studies. The primary...... may also be associated with ovarian and breast cancer susceptibility. However, the effects are modest and warrant replication in larger studies Udgivelsesdato: 2008/11/1...

  10. Use of Exogenous Progestins and Risk of In Situ and Invasive Breast Cancer

    National Research Council Canada - National Science Library

    Li, Christopher I

    2006-01-01

    Given the large number of women exposed to progestins through either contraceptives or menopausal hormone therapies, clarifying the etiologic role of progestin in relation to breast cancer is of public health importance...

  11. Trastuzumab Exposure in Early Pregnancy for a Young Lady With Locally Invasive Breast Cancer.

    Science.gov (United States)

    Pianca, Natasha; Shafiei, Mohsen; George, Mathew

    2015-06-01

    Due to the lack of literature on the effects of trastuzumab in pregnancy, an interest has been taken in a patient that incidentally became pregnant while on adjuvant treatment in the first trimester following diagnosis of locally advanced breast cancer.

  12. Trastuzumab Exposure in Early Pregnancy for a Young Lady With Locally Invasive Breast Cancer

    OpenAIRE

    Pianca, Natasha; Shafiei, Mohsen; George, Mathew

    2015-01-01

    Due to the lack of literature on the effects of trastuzumab in pregnancy, an interest has been taken in a patient that incidentally became pregnant while on adjuvant treatment in the first trimester following diagnosis of locally advanced breast cancer.

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

    Science.gov (United States)

    2004-08-01

    messenger RNA level during breast carcinogenesis. Cancer Res 1997, 57:4992-4996 8. Lawrence JA, Merino MJ, Simpson JF, Manrow RE, Page DL, Steeg PS: A high...Kurek R, Wallwiener D, Merino MJ, Petricoin EF, 3rd, Zhao Y, Steeg PS: Proteomics of human breast ductal carcinoma in situ. Cancer Res 2002, 62:6740...JJ, Davenport GJ, Orenstein JM, Gutierrez P, Simmens SJ, Abraham J, Poola I, Stephan DA, Berg PE. Correlation of expression of BP1, a homeobox gene

  14. Hypofractionated Radiation Therapy After Mastectomy in Preventing Recurrence in Patients With Stage IIa-IIIa Breast Cancer

    Science.gov (United States)

    2018-04-06

    Ductal Breast Carcinoma; Invasive Breast Carcinoma; Lobular Breast Carcinoma; Medullary Breast Carcinoma; Stage II Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Tubular Breast Carcinoma

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  17. Lobular carcinoma in situ and invasive lobular breast cancer are characterized by enhanced expression of transcription factor AP-2β.

    Science.gov (United States)

    Raap, Mieke; Gronewold, Malte; Christgen, Henriette; Glage, Silke; Bentires-Alj, Mohammad; Koren, Shany; Derksen, Patrick W; Boelens, Mirjam; Jonkers, Jos; Lehmann, Ulrich; Feuerhake, Friedrich; Kuehnle, Elna; Gluz, Oleg; Kates, Ronald; Nitz, Ulrike; Harbeck, Nadia; Kreipe, Hans H; Christgen, Matthias

    2018-01-01

    Transcription factor AP-2β (TFAP2B) regulates embryonic organ development and is overexpressed in alveolar rhabdomyosarcoma, a rare childhood malignancy. Gene expression profiling has implicated AP-2β in breast cancer (BC). This study characterizes AP-2β expression in the mammary gland and in BC. AP-2β protein expression was assessed in the normal mammary gland epithelium, in various reactive, metaplastic and pre-invasive neoplastic lesions and in two clinical BC cohorts comprising >2000 patients. BCs from various genetically engineered mouse (GEM) models were also evaluated. Human BC cell lines served as functional models to study siRNA-mediated inhibition of AP-2β. The normal mammary gland epithelium showed scattered AP-2β-positive cells in the luminal cell layer. Various reactive and pre-invasive neoplastic lesions, including apocrine metaplasia, usual ductal hyperplasia and lobular carcinoma in situ (LCIS) showed enhanced AP-2β expression. Cases of ductal carcinoma in situ (DCIS) were more often AP-2β-negative (Pinvasive BC cohorts, AP-2β-positivity was associated with the lobular BC subtype (Plobular BC cell lines in vitro. In summary, AP-2β is a new mammary epithelial differentiation marker. Its expression is preferentially retained and enhanced in LCIS and invasive lobular BC and has prognostic implications. Our findings indicate that AP-2β controls tumor cell proliferation in this slow-growing BC subtype.

  18. The Function of Vacuolar ATPase (V-ATPase) a Subunit Isoforms in Invasiveness of MCF10a and MCF10CA1a Human Breast Cancer Cells*

    Science.gov (United States)

    Capecci, Joseph; Forgac, Michael

    2013-01-01

    The vacuolar H+ ATPases (V-ATPases) are ATP-driven proton pumps that transport protons across both intracellular and plasma membranes. Previous studies have implicated V-ATPases in the invasiveness of various cancer cell lines. In this study, we evaluated the role of V-ATPases in the invasiveness of two closely matched human breast cancer lines. MCF10a cells are a non-invasive, immortalized breast epithelial cell line, and MCF10CA1a cells are a highly invasive, H-Ras-transformed derivative of MCF10a cells selected for their metastatic potential. Using an in vitro Matrigel assay, MCF10CA1a cells showed a much higher invasion than the parental MCF10a cells. Moreover, this increased invasion was completely sensitive to the specific V-ATPase inhibitor concanamycin. MCF10CA1a cells expressed much higher levels of both a1 and a3 subunit isoforms relative to the parental line. Isoforms of subunit a are responsible for subcellular localization of V-ATPases, with a3 and a4 targeting V-ATPases to the plasma membrane of specialized cells. Knockdown of either a3 alone or a3 and a4 together using isoform-specific siRNAs inhibited invasion by MCF10CA1a cells. Importantly, overexpression of a3 but not the other a subunit isoforms greatly increased the invasiveness of the parental MCF10a cells. Similarly, overexpression of a3 significantly increased expression of V-ATPases at the plasma membrane. These studies suggest that breast tumor cells employ particular a subunit isoforms to target V-ATPases to the plasma membrane, where they function in tumor cell invasion. PMID:24072707

  19. The function of vacuolar ATPase (V-ATPase) a subunit isoforms in invasiveness of MCF10a and MCF10CA1a human breast cancer cells.

    Science.gov (United States)

    Capecci, Joseph; Forgac, Michael

    2013-11-08

    The vacuolar H(+) ATPases (V-ATPases) are ATP-driven proton pumps that transport protons across both intracellular and plasma membranes. Previous studies have implicated V-ATPases in the invasiveness of various cancer cell lines. In this study, we evaluated the role of V-ATPases in the invasiveness of two closely matched human breast cancer lines. MCF10a cells are a non-invasive, immortalized breast epithelial cell line, and MCF10CA1a cells are a highly invasive, H-Ras-transformed derivative of MCF10a cells selected for their metastatic potential. Using an in vitro Matrigel assay, MCF10CA1a cells showed a much higher invasion than the parental MCF10a cells. Moreover, this increased invasion was completely sensitive to the specific V-ATPase inhibitor concanamycin. MCF10CA1a cells expressed much higher levels of both a1 and a3 subunit isoforms relative to the parental line. Isoforms of subunit a are responsible for subcellular localization of V-ATPases, with a3 and a4 targeting V-ATPases to the plasma membrane of specialized cells. Knockdown of either a3 alone or a3 and a4 together using isoform-specific siRNAs inhibited invasion by MCF10CA1a cells. Importantly, overexpression of a3 but not the other a subunit isoforms greatly increased the invasiveness of the parental MCF10a cells. Similarly, overexpression of a3 significantly increased expression of V-ATPases at the plasma membrane. These studies suggest that breast tumor cells employ particular a subunit isoforms to target V-ATPases to the plasma membrane, where they function in tumor cell invasion.

  20. Society of Surgical Oncology–American Society for Radiation Oncology Consensus Guideline on Margins for Breast-Conserving Surgery With Whole-Breast Irradiation in Stages I and II Invasive Breast Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Moran, Meena S. [Department of Therapeutic Radiology, Yale School of Medicine, Yale University, New Haven, Connecticut (United States); Schnitt, Stuart J. [Department of Pathology, Harvard Medical School, Boston, Massachusetts (United States); Giuliano, Armando E. [Department of Surgery, Cedars Sinai Medical Center, Los Angeles, California (United States); Harris, Jay R. [Department of Radiation Oncology, Harvard Medical School, Boston, Massachusetts (United States); Khan, Seema A. [Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois (United States); Horton, Janet [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States); Klimberg, Suzanne [Department of Surgery, University of Arkansas for Medical Sciences, Fayetteville, Arkansas (United States); Chavez-MacGregor, Mariana [Department of Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Freedman, Gary [Department of Radiation Oncology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania (United States); Houssami, Nehmat [School of Public Health, Sydney Medical School, University of Sydney, Sydney, New South Wales (Australia); Johnson, Peggy L. [Advocate in Science, Susan G. Komen, Wichita, Kansas (United States); Morrow, Monica, E-mail: morrowm@mskcc.org [Breast Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York (United States)

    2014-03-01

    Purpose: To convene a multidisciplinary panel of breast experts to examine the relationship between margin width and ipsilateral breast tumor recurrence (IBTR) and develop a guideline for defining adequate margins in the setting of breast conserving surgery and adjuvant radiation therapy. Methods and Materials: A multidisciplinary consensus panel used a meta-analysis of margin width and IBTR from a systematic review of 33 studies including 28,162 patients as the primary evidence base for consensus. Results: Positive margins (ink on invasive carcinoma or ductal carcinoma in situ) are associated with a 2-fold increase in the risk of IBTR compared with negative margins. This increased risk is not mitigated by favorable biology, endocrine therapy, or a radiation boost. More widely clear margins than no ink on tumor do not significantly decrease the rate of IBTR compared with no ink on tumor. There is no evidence that more widely clear margins reduce IBTR for young patients or for those with unfavorable biology, lobular cancers, or cancers with an extensive intraductal component. Conclusions: The use of no ink on tumor as the standard for an adequate margin in invasive cancer in the era of multidisciplinary therapy is associated with low rates of IBTR and has the potential to decrease re-excision rates, improve cosmetic outcomes, and decrease health care costs.

  1. Positive Association of Fibroadenomatoid Change with HER2-Negative Invasive Breast Cancer: A Co-Occurrence Study

    Science.gov (United States)

    Kovatich, Albert J.; Hooke, Jeffrey A.; Liu, Jianfang; Kvecher, Leonid; Fantacone-Campbell, J. Leigh; Mitchell, Edith P.; Rui, Hallgeir; Shriver, Craig D.; Hu, Hai

    2015-01-01

    Background Risk assessment of a benign breast disease/lesion (BBD) for invasive breast cancer (IBC) is typically done through a longitudinal study. For an infrequently-reported BBD, the shortage of occurrence data alone is a limiting factor to conducting such a study. Here we present an approach based on co-occurrence analysis, to help address this issue. We focus on fibroadenomatoid change (FAC), an under-studied BBD, as our preliminary analysis has suggested its previously unknown significant co-occurrence with IBC. Methods A cohort of 1667 female patients enrolled in the Clinical Breast Care Project was identified. A single experienced breast pathologist reviewed all pathology slides for each case and recorded all observed lesions, including FAC. Fibroadenoma (FA) was studied for comparison since FAC had been speculated to be an immature FA. FA and Fibrocystic Changes (FCC) were used for method validation since they have been comprehensively studied. Six common IBC and BBD risk/protective factors were also studied. Co-occurrence analyses were performed using logistic regression models. Results Common risk/protective factors were associated with FA, FCC, and IBC in ways consistent with the literature in general, and they were associated with FAC, FA, and FCC in distinct patterns. Age was associated with FAC in a bell-shape curve so that middle-aged women were more likely to have FAC. We report for the first time that FAC is positively associated with IBC with odds ratio (OR) depending on BMI (OR = 6.78, 95%CI = 3.43-13.42 at BMI25 kg/m2). This association is only significant with HER2-negative IBC subtypes. Conclusions We conclude that FAC is a candidate risk factor for HER2-negative IBCs, and it is a distinct disease from FA. Co-occurrence analysis can be used for initial assessment of the risk for IBC from a BBD, which is vital to the study of infrequently-reported BBDs. PMID:26098961

  2. Positive Association of Fibroadenomatoid Change with HER2-Negative Invasive Breast Cancer: A Co-Occurrence Study.

    Directory of Open Access Journals (Sweden)

    Yaqin Chen

    Full Text Available Risk assessment of a benign breast disease/lesion (BBD for invasive breast cancer (IBC is typically done through a longitudinal study. For an infrequently-reported BBD, the shortage of occurrence data alone is a limiting factor to conducting such a study. Here we present an approach based on co-occurrence analysis, to help address this issue. We focus on fibroadenomatoid change (FAC, an under-studied BBD, as our preliminary analysis has suggested its previously unknown significant co-occurrence with IBC.A cohort of 1667 female patients enrolled in the Clinical Breast Care Project was identified. A single experienced breast pathologist reviewed all pathology slides for each case and recorded all observed lesions, including FAC. Fibroadenoma (FA was studied for comparison since FAC had been speculated to be an immature FA. FA and Fibrocystic Changes (FCC were used for method validation since they have been comprehensively studied. Six common IBC and BBD risk/protective factors were also studied. Co-occurrence analyses were performed using logistic regression models.Common risk/protective factors were associated with FA, FCC, and IBC in ways consistent with the literature in general, and they were associated with FAC, FA, and FCC in distinct patterns. Age was associated with FAC in a bell-shape curve so that middle-aged women were more likely to have FAC. We report for the first time that FAC is positively associated with IBC with odds ratio (OR depending on BMI (OR = 6.78, 95%CI = 3.43-13.42 at BMI25 kg/m2. This association is only significant with HER2-negative IBC subtypes.We conclude that FAC is a candidate risk factor for HER2-negative IBCs, and it is a distinct disease from FA. Co-occurrence analysis can be used for initial assessment of the risk for IBC from a BBD, which is vital to the study of infrequently-reported BBDs.

  3. Initial Results of a Prospective Clinical Trial of 18F-Fluciclovine PET/CT in Newly Diagnosed Invasive Ductal and Invasive Lobular Breast Cancers.

    Science.gov (United States)

    Ulaner, Gary A; Goldman, Debra A; Gönen, Mithat; Pham, Hanh; Castillo, Raychel; Lyashchenko, Serge K; Lewis, Jason S; Dang, Chau

    2016-09-01

    (18)F-labeled 1-amino-3-fluorocyclobutane-1-carboxylic acid ((18)F-fluciclovine) is a leucine analog PET/CT radiotracer that depicts amino acid transport into cells. Amino acid transport proteins have been shown to be upregulated in breast malignancies by microarray and immunohistochemical analysis, so we hypothesized that (18)F-fluciclovine may provide a novel method of visualizing breast cancer and now report a prospective clinical trial of (18)F-fluciclovine PET/CT in newly diagnosed advanced local invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC). Twenty-seven women with a new diagnosis of locally advanced IDC (n = 19) or ILC (n = 8) underwent PET/CT of the chest after intravenous administration of 370 MBq of (18)F-fluciclovine. The SUVmax, SUVmean, metabolic tumor volume, and total lesion avidity were obtained for the primary breast tumor, axillary lymph nodes, and extraaxillary lymph nodes. Sites of previously unsuspected malignancy were recorded and confirmed by pathology. Results of (18)F-fluciclovine PET/CT were compared with those of (18)F-FDG PET/CT, when available, using the concordance correlation coefficient. All locally advanced breast cancers were (18)F-fluciclovine-avid. Of 21 patients with pathologically proven axillary nodal metastases, (18)F-fluciclovine-avid axillary nodes were seen in 20. (18)F-fluciclovine detected pathologically proven extraaxillary nodal metastases in 3 patients, including 2 previously unsuspected internal mammary nodes. Fourteen patients underwent (18)F-FDG PET/CT for comparison with (18)F-fluciclovine. Concordance for metabolic tumor volume between (18)F-fluciclovine and (18)F-FDG was strong (concordance correlation coefficient, 0.89; 95% confidence interval, 0.73-0.96), but concordance for SUVmax was weak (concordance correlation coefficient, 0.04; 95% confidence interval, -0.16-0.24). In patients with both modalities available (n = 14), primary ILCs (n = 4) demonstrated (18)F-fluciclovine avidity

  4. Patients with invasive lobular breast cancer are less likely to undergo breast-conserving surgery: a population based study in the Netherlands.

    Science.gov (United States)

    Truin, W; Roumen, R M; Siesling, S; van der Heiden-van der Loo, M; Duijm, L E M; Tjan-Heijnen, V C G; Voogd, A C

    2015-05-01

    The aim of this study was to compare the frequency of breast-conserving surgery (BCS) between early-stage invasive ductal (IDC) and invasive lobular breast cancer (ILC). Women with primary non-metastatic pT1 and pT2 IDC or ILC diagnosed between 1990 and 2010 were selected from the NCR. All patients underwent BCS or primary mastectomy without neoadjuvant treatment and proportions per year were calculated. Logistic regression analysis with adjustment for period, age, nodal status and tumor size was performed to determine the impact of histology on the likelihood of undergoing BCS. A total of 152,574 patients underwent surgery in the period between 1990 and 2010, of which 89 % had IDC and 11 % had ILC. In the group of IDC with pT1 and pT2 tumors combined, 54 % underwent BCS compared with 43 % of patients with ILC (p < 0.0001). The proportion of patients with IDC treated by BCS increased from 46 % in 1990 to 62 % in 2010. The BCS rate among ILC patients increased from 39 % in 1990 to 48 % in 2010. Patients with ILC were less likely to undergo BCS compared with patients with IDC (odds ratio 0.69; 95 % confidence interval 0.66-0.71). The incidence of BCS for patients with IDC or ILC is rising in The Netherlands. However, the increase of BCS is less explicit in patients with ILC, with a higher chance of undergoing mastectomy compared with patients with IDC.

  5. Long-term results of breast conserving surgery vs. mastectomy for early stage invasive breast cancer: 20-year follow-up of the Danish randomized DBCG-82TM protocol

    DEFF Research Database (Denmark)

    Blichert-Toft, M.; Nielsen, M.; During, M.

    2008-01-01

    The main objective of the present study aims at comparing the long-term efficacy of breast conserving surgery (BCS) vs. mastectomy (M) based on a randomized design. The Danish Breast Cancer Cooperative Group (DBCG) conducted the trial (DBCG-82TM) from January 1983 to March 1989 recruiting 1154...... patients with invasive breast carcinoma. Follow-up time ended 1(st) May 2006 with a median follow-up time of 19.6 years (time span 17.1-23.3 years). Eligibility criteria included a one-sided, unifocal, primary operable breast carcinoma, patient age below 70 years, probability of satisfactory cosmetic......% of the complete series. 10-year recurrence free survival (RFS) and 20-year overall survival (OS) based on intent to treat did not reveal significant differences in outcome between breast conserving surgery vs. mastectomy, p=0.95 and p=0.10, respectively. Including the complete series comprising 1133 eligible...

  6. Morphine does not facilitate breast cancer progression in two preclinical mouse models for human invasive lobular and HER2⁺ breast cancer.

    Science.gov (United States)

    Doornebal, Chris W; Vrijland, Kim; Hau, Cheei-Sing; Coffelt, Seth B; Ciampricotti, Metamia; Jonkers, Jos; de Visser, Karin E; Hollmann, Markus W

    2015-08-01

    Morphine and other opioid analgesics are potent pain-relieving agents routinely used for pain management in patients with cancer. However, these drugs have recently been associated with a worse relapse-free survival in patients with surgical cancer, thus suggesting that morphine adversely affects cancer progression and relapse. In this study, we evaluated the impact of morphine on breast cancer progression, metastatic dissemination, and outgrowth of minimal residual disease. Using preclinical mouse models for metastatic invasive lobular and HER2 breast cancer, we show that analgesic doses of morphine do not affect mammary tumor growth, angiogenesis, and the composition of tumor-infiltrating immune cells. Our studies further demonstrate that morphine, administered in the presence or absence of surgery-induced tissue damage, neither facilitates de novo metastatic dissemination nor promotes outgrowth of minimal residual disease after surgery. Together, these findings indicate that opioid analgesics can be used safely for perioperative pain management in patients with cancer and emphasize that current standards of "good clinical practice" should be maintained.

  7. Detection of lymphovascular invasion in early breast cancer by D2-40 (podoplanin): a clinically useful predictor for axillary lymph node metastases.

    NARCIS (Netherlands)

    Braun, M.; Flucke, U.E.; Debald, M.; Walgenbach-Bruenagel, G.; Walgenbach, K.J.; Holler, T.; Polcher, M.; Wolfgarten, M.; Sauerwald, A.; Keyver-Paik, M.; Kuhr, M.; Buttner, R.; Kuhn, W.

    2008-01-01

    PURPOSE: The aim of this study was to investigate the use of D2-40 for the detection of lymphovascular invasion (LVI) in node positive and negative early breast cancer. LVI is associated with axillary lymph node metastases (ALNM) and a long-term prognostic factor. A precise identification of LVI

  8. Correlation between E-cadherin and p120 expression in invasive ductal breast cancer with a lobular component and MRI findings

    NARCIS (Netherlands)

    El Sharouni, Mary Ann; Postma, Emily L.; van Diest, Paul J.

    2017-01-01

    Invasive breast cancer comprises a spectrum of histological changes with purely lobular cancer on one side and purely ductal cancer on the other, with many mixed lesions in between. In a previous study, we showed that in patients with any percentage lobular component at core needle biopsy,

  9. ErbB2-Driven Breast Cancer Cell Invasion Depends on a Complex Signaling Network Activating Myeloid Zinc Finger-1-Dependent Cathepsin B Expression

    DEFF Research Database (Denmark)

    Rafn, Bo; Nielsen, Christian Thomas Friberg; Andersen, Sofie Hagel

    2012-01-01

    signaling network activates the transcription of cathepsin B gene (CTSB) via myeloid zinc finger-1 transcription factor that binds to an ErbB2-responsive enhancer element in the first intron of CTSB. This work provides a model system for ErbB2-induced breast cancer cell invasiveness, reveals a signaling...

  10. P2Y2 receptor promotes the migration and invasion of breast cancer cells via EMT-related genes Snail and E-cadherin.

    Science.gov (United States)

    Qiu, Ying; Liu, Yan; Li, Wei-Hua; Zhang, Hong-Quan; Tian, Xin-Xia; Fang, Wei-Gang

    2018-01-01

    Adenosine 5'-triphosphate (ATP) is one of the most abundant biochemical constituents within the tumor microenvironment and is postulated to play critical roles in the progression of a number of types of tumors via interaction with the P2Y2 receptor. In the present study, we demonstrated that the P2Y2 receptor was highly expressed in MCF7 and Hs578T breast cancer cells. Downregulation of the P2Y2 receptor by small interfering RNA (siRNA) significantly attenuated ATP- or UTP-driven migration and invasion of the breast cancer cells as well as expression of EMT-related genes Snail and E-cadherin. Consistent with the observations in vitro, the P2Y2 receptor was found to be abundantly expressed at the invasive edge of the tumor, in infiltrating tumor cells in breast adipose tissues and/or the cancer embolus in the lymphatic sinuses compared with the tumor core areas. Furthermore, high Snail expression and weak or negative expression of E-cadherin were observed at the invasive edge of tumors. Taken together, these data indicate that the P2Y2 receptor promoted cell migration and invasion in breast cancer cells via EMT-related genes Snail and E-cadherin.

  11. Shear-wave elastography and immunohistochemical profiles in invasive breast cancer: Evaluation of maximum and mean elasticity values

    International Nuclear Information System (INIS)

    Ganau, Sergi; Andreu, Francisco Javier; Escribano, Fernanda; Martín, Amaya; Tortajada, Lidia; Villajos, Maite

    2015-01-01

    Highlights: •Shear wave elastography provides a quantitative assessment of the hardness of breast lesions. •The hardness of breast lesions correlates with lesion size: larger lesions are harder than smaller ones. •Histologic type and grade do not correlate clearly with elastography parameters. •HER2, luminal B HER2+, and triple-negative tumors have lower maximum hardness and mean hardness than other tumor types. •Half the tumors classified as BI-RADS 3 were luminal A and half were HER2. -- Abstract: Purpose: To evaluate the correlations of maximum stiffness (Emax) and mean stiffness (Emean) of invasive carcinomas on shear-wave elastography (SWE) with St. Gallen consensus tumor phenotypes. Methods: We used an ultrasound system with SWE capabilities to prospectively study 190 women with 216 histologically confirmed invasive breast cancers. We obtained one elastogram for each lesion. We correlated Emax and Emean with tumor size, histologic type and grade, estrogen and progesterone receptors, HER2 expression, the Ki67 proliferation index, and the five St. Gallen molecular subtypes: luminal A, luminal B without HER2 overexpression (luminal B HER2−), luminal B with HER2 overexpression (luminal B HER2+), HER2, and triple negative. Results: Lesions larger than 20 mm had significantly higher Emax (148.04 kPa) and Emean (118.32 kPa) (P = 0.005) than smaller lesions. We found no statistically significant correlations between elasticity parameters and histologic type and grade or molecular subtypes, although tumors with HER2 overexpression regardless whether they expressed hormone receptors (luminal B HER2+ and HER2 phenotypes) and triple-negative tumors had lower Emax and Emean than the others. We assessed the B-mode ultrasound findings of the lesions with some of the Emax or Emean values less than or equal to 80 kPa; only four of these had ultrasound findings suggestive of a benign lesion (two with luminal A phenotype and two with HER2 phenotype). Conclusions: We

  12. Shear-wave elastography and immunohistochemical profiles in invasive breast cancer: Evaluation of maximum and mean elasticity values

    Energy Technology Data Exchange (ETDEWEB)

    Ganau, Sergi, E-mail: sganau@tauli.cat [Women' s Imaging Department, UDIAT-Centre Diagnòstic, Institut Universitari Parc Taulí – UAB, Parc Taulí, 1, 08205 Sabadell, Barcelona (Spain); Andreu, Francisco Javier, E-mail: xandreu@tauli.cat [Pathology Department, UDIAT-Centre Diagnòstic, Institut Universitari Parc Taulí – UAB, Parc Taulí, 1, 08205 Sabadell, Barcelona (Spain); Escribano, Fernanda, E-mail: fescribano@tauli.cat [Women' s Imaging Department, UDIAT-Centre Diagnòstic, Institut Universitari Parc Taulí – UAB, Parc Taulí, 1, 08205 Sabadell, Barcelona (Spain); Martín, Amaya, E-mail: amartino@tauli.cat [Women' s Imaging Department, UDIAT-Centre Diagnòstic, Institut Universitari Parc Taulí – UAB, Parc Taulí, 1, 08205 Sabadell, Barcelona (Spain); Tortajada, Lidia, E-mail: ltortajada@tauli.cat [Women' s Imaging Department, UDIAT-Centre Diagnòstic, Institut Universitari Parc Taulí – UAB, Parc Taulí, 1, 08205 Sabadell, Barcelona (Spain); Villajos, Maite, E-mail: mvillajos@tauli.cat [Women' s Imaging Department, UDIAT-Centre Diagnòstic, Institut Universitari Parc Taulí – UAB, Parc Taulí, 1, 08205 Sabadell, Barcelona (Spain); and others

    2015-04-15

    Highlights: •Shear wave elastography provides a quantitative assessment of the hardness of breast lesions. •The hardness of breast lesions correlates with lesion size: larger lesions are harder than smaller ones. •Histologic type and grade do not correlate clearly with elastography parameters. •HER2, luminal B HER2+, and triple-negative tumors have lower maximum hardness and mean hardness than other tumor types. •Half the tumors classified as BI-RADS 3 were luminal A and half were HER2. -- Abstract: Purpose: To evaluate the correlations of maximum stiffness (Emax) and mean stiffness (Emean) of invasive carcinomas on shear-wave elastography (SWE) with St. Gallen consensus tumor phenotypes. Methods: We used an ultrasound system with SWE capabilities to prospectively study 190 women with 216 histologically confirmed invasive breast cancers. We obtained one elastogram for each lesion. We correlated Emax and Emean with tumor size, histologic type and grade, estrogen and progesterone receptors, HER2 expression, the Ki67 proliferation index, and the five St. Gallen molecular subtypes: luminal A, luminal B without HER2 overexpression (luminal B HER2−), luminal B with HER2 overexpression (luminal B HER2+), HER2, and triple negative. Results: Lesions larger than 20 mm had significantly higher Emax (148.04 kPa) and Emean (118.32 kPa) (P = 0.005) than smaller lesions. We found no statistically significant correlations between elasticity parameters and histologic type and grade or molecular subtypes, although tumors with HER2 overexpression regardless whether they expressed hormone receptors (luminal B HER2+ and HER2 phenotypes) and triple-negative tumors had lower Emax and Emean than the others. We assessed the B-mode ultrasound findings of the lesions with some of the Emax or Emean values less than or equal to 80 kPa; only four of these had ultrasound findings suggestive of a benign lesion (two with luminal A phenotype and two with HER2 phenotype). Conclusions: We

  13. Role of Crk Adaptor Proteins in Cellular Migration and Invasion in Human Breast Cancer

    National Research Council Canada - National Science Library

    Fathers, Kelly E

    2007-01-01

    The Crk adaptor proteins (CrkI, CrkII and CrkL) play an important role during cellular signalling by mediating the formation of protein-protein complexes and are involved in cellular migration, invasion, and adhesion...

  14. Role of Crk Adaptor Proteins in Cellular Migration and Invasion in Human Breast Cancer

    National Research Council Canada - National Science Library

    Fathers, Kelly E

    2008-01-01

    The Crk adaptor proteins (CrkI, CrkII and CrkL) play an important role during cellular signalling by mediating the formation of protein-protein complexes and are involved in cellular migration, invasion, and adhesion...

  15. Role of Crk Adaptor Proteins in Cellular Migration and Invasion in Human Breast Cancer

    National Research Council Canada - National Science Library

    Fathers, Kelly E

    2008-01-01

    .... As migration and invasion are important components of the metastatic cascade, future work includes performing in vivo metastasis assays using cells with stably knocked down expression of Crk proteins...

  16. [The effect of leptin and its mechanisms on the migration and invasion of human breast cancer MCF-7 cells].

    Science.gov (United States)

    Wang, Lin; Cao, Hong; Pang, Xueli; Li, Kuangfa; Dang, Weiqi; Tang, Hao; Chen, Tingmei

    2013-12-01

    To investigate the effect and the relevant molecular mechanisms of leptin on the migration and invasion of human breast cancer MCF-7 cells. The expression of OB-R in MCF-7 cells was measured by RT-PCR and Western blotting. The effects of leptin (100 ng/mL) on the the phosphorylation of a few key cell signaling proteins, p-ERK1/2, p-STAT3, p-AKT in MCF-7 cells were examined by Western blotting. Cell scratch assay and Transwell(TM); assay were utilized to measure the effects of leptin on the migration and invasion capability of MCF-7 cells, respectively. The effects of leptin on the mRNA and protein expression of matrix metalloproteinas 9 (MMP-9) and transforming growth factor β (TGF-β) were measured by RT-PCR and Western blotting. Both OB-Rb and OB-Rt were expressed in MCF-7 cells. This indicated that leptin may have significant activities in MCF7 cells. Indeed, leptin increased the phosphorylation of p-ERK1/2, p-STAT3, and p-AKT in MCF-7 cells (P < 0.05). Further, leptin promoted migration and invasion of MCF-7 cells, which were attenuated by the JAK/STAT inhibitor AG490 (50 μmol/L), and the PI3K/AKT inhibitor LY294002 (10 μmol/L) (P < 0.05). Similarly, leptin also increased the mRNA and protein expression of MMP-9 and TGF-β, and these effects were blocked by AG490 and LY294002 as well (P < 0.05). Leptin promoted the migration and invasion capabilities of MCF-7 cells. These activities may be achieved by the upregulation of MMP-9 and TGF-β through JAK/STAT and PI3K/AKT signaling pathways.

  17. Docosahexaenoic Acid in Preventing Recurrence in Breast Cancer Survivors

    Science.gov (United States)

    2016-06-20

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

  18. Retroviral delivery of TIMP-2 inhibits H-ras-induced migration and invasion in MCF10A human breast epithelial cells.

    Science.gov (United States)

    Ahn, Seong-Min; Jeong, Seo-Jin; Kim, Yeon-Soo; Sohn, Yeowon; Moon, Aree

    2004-04-15

    The matrix metalloproteases (MMPs) play important roles in invasion, metastasis and angiogenesis in various cell types. Tissue inhibitor of metalloprotease (TIMP)-2, an endogenous inhibitor of MMP-2, has been shown to inhibit invasion and metastasis. We have previously shown that MMP-2 is responsible for the H-ras-induced invasive and migrative phenotypes in MCF10A human breast epithelial cells. Here, we investigated the effect of TIMP-2 overexpression on migration and invasion in H-ras MCF10A cells. Human TIMP-2 gene was effectively introduced into H-ras MCF10A cells by retrovirus-mediated gene delivery. TIMP-2 overexpression mediated by retrovirus significantly inhibited migration as well as invasion of H-ras MCF10A cells in a dose-dependent manner. We also show the antiangiogenic effect of TIMP-2 gene delivery. Taken together, our study shows that retrovirus-mediated delivery of TIMP-2 efficiently inhibits metastatic progression of ras-transformed human breast epithelial cells, suggesting a potential use of the TIMP-2 gene therapy for the treatment of breast cancer.

  19. 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.

  20. The Role of MicroRNAs in Breast Cancer Migration, Invasion and Metastasis

    Directory of Open Access Journals (Sweden)

    Joy Tang

    2012-10-01

    Full Text Available MicroRNAs (miRNAs are a major class of small, noncoding RNA molecules that regulate gene expression by targeting mRNAs to trigger either translational repression or mRNA degradation. They have recently been more widely investigated due to their potential role as targets for cancer therapy. Many miRNAs have been implicated in several human cancers, including breast cancer. miRNAs are known to regulate cell cycle and development, and thus may serve as useful targets for exploration in anticancer therapeutics. The link between altered miRNA signatures and breast cancer development and metastasis can be observed either through the loss of tumor suppressor miRNAs, such as let-7s, miR-30a/31/34a/125s/200s/203/205/206/342 or the overexpression of oncogenic miRNAs, such as miR-10b/21/135a/155/221/222/224/373/520c in breast cancer cells. Some of these miRNAs have also been validated in tumor specimens of breast cancer patients, underscoring their potential roles in diagnostics, as well as targets for novel therapeutics for breast cancer. In this review article, we will provide an overview and update of our current understanding of the mode of action of several of these well characterized miRNAs in breast cancer models. Therefore, better understanding of the gene networks orchestrated by these miRNAs may help exploit the full potential of miRNAs in regards to cancer diagnosis, treatment, and therapeutics.

  1. The diagnosis and management of pre-invasive breast disease: Flat epithelial atypia – classification, pathologic features and clinical significance

    International Nuclear Information System (INIS)

    Schnitt, Stuart J

    2003-01-01

    Flat epithelial atypia is a descriptive term that encompasses lesions of the breast terminal duct lobular units in which variably dilated acini are lined by one to several layers of epithelial cells, which are usually columnar in shape and which display low-grade cytologic atypia. Observational studies have suggested that at least some of these lesions may represent either a precursor of ductal carcinoma in situ (DCIS) or the earliest morphological manifestation of DCIS. In contrast, the limited available clinical follow-up data suggest that the risk of both local recurrence and progression of these lesions to invasive cancer is extremely low, supporting the notion that categorizing such lesions as 'clinging carcinoma' and managing them as if they were fully developed DCIS will result in overtreatment of many patients. Additional studies are needed to better understand the biological nature and clinical significance of these lesions

  2. The diagnosis and management of pre-invasive breast disease: Pathological diagnosis – problems with existing classifications

    International Nuclear Information System (INIS)

    Van de Vijver, Marc J; Peterse, Hans

    2003-01-01

    In this review, we comment on the reasons for disagreement in the concepts, diagnosis and classifications of pre-invasive intraductal proliferations. In view of these disagreements, our proposal is to distinguish epithelial hyperplasia, lobular carcinoma in situ and ductal carcinoma in situ, and to abandon the use of poorly reproducible categories, such as atypical ductal hyperplasia or ductal intraepithelial neoplasia, followed by a number to indicate the degree of proliferation and atypia, as these are not practical for clinical decision making, nor for studies aimed at improving the understanding of breast cancer development. If there is doubt about the classification of an intraductal proliferation, a differential diagnosis and the reason for and degree of uncertainty should be given, rather than categorizing a proliferation as atypical

  3. A comparison of different non-invasive screening methods in the diagnosis of stage T1 breast cancer

    International Nuclear Information System (INIS)

    Bartl, W.; Euller, A.; Pfersmann, C.; Bernaschek, G.; Breitenecker, G.

    1984-01-01

    52 women with stage T 1 breast cancer were investigated by thermography, mammography and ultrasound and the results compared with the patients age, histological tumour type and the degree of malignancy. The best results were achieved by mammography (sensitivity: 85%). In tumours with a large amount of connective tissue (scirrhous or invasive lobular cancer) sensitivity rose to 94%, whilst in tumours with little connective tissue (solid, medullary, adenomatous and papillary) sensitivity decreased to 69%. The respective values for thermographic sensitivity were 44% and 77% and for ultrasound sensitivity in palpable tumours 85% and 65%, respectively. On mammography 3 carcinomas were not recognized, all three in younger patients; on thermography also three false negative results were obtained, but all in older patients. The sensitivity of thermography increases in parallel with increasing degree of tumour malignancy. Whilst ultrasound is a valuable aid for differential diagnosis in palpable tumours only, screening results can evidently be improved by a combination of thermography and mammography. (Author)

  4. Expression of e-cadherin, n-cadherin and snail and their correlation with clinicopathological variants: an immunohistochemical study of 132 invasive ductal breast carcinomas in Egypt

    Directory of Open Access Journals (Sweden)

    Hanan Mohamed Abd ElMoneim

    2011-01-01

    Full Text Available OBJECTIVE: To evaluate the expression of the cell adhesion molecules E-cadherin and N-cadherin and the transcription factor Snail in invasive ductal breast carcinomas and to determine their relationships with clinicopathological features. METHODS: Immunohistochemistry was used to examine E-cadherin, N-cadherin, and Snail protein expression in 132 invasive breast carcinomas. RESULTS: The expression of E-cadherin was decreased (negative or weak in 37.1% of invasive carcinomas, while N-cadherin and Snail overexpression were detected in 51.9% and 40.9% of carcinomas, respectively. Low E-cadherin expression was significantly correlated with poorly differentiated carcinoma (53.1%, positive node status (80.9%, poor Nottingham Prognostic Index (64.7%, and the presence of estrogen and progesterone receptors. Overexpression of N-cadherin and Snail were also significantly correlated with poorly differentiated carcinoma, positive node status, and poor Nottingham Prognostic Index but were correlated with the absence of hormone receptors. Loss of E-cadherin immunoexpression was strongly associated with the presence of membranous N-cadherin (87.8% and nuclear Snail (69.4%. CONCLUSION: Loss of E-cadherin and overexpression of N-cadherin and Snail in breast carcinomas may play a central role in the development of invasive ductal breast carcinoma. These biomarkers may provide a valuable reference for the study of invasive ductal carcinoma progression and to characterize the biological behavior of the tumor. In the future, increased N-cadherin and decreased E-cadherin expression may be used as indicators of the progression and prognosis of invasive ductal carcinoma.

  5. Hypoxia-inducible factor-2a is associated with ABCG2 expression, histology-grade and Ki67 expression in breast invasive ductal carcinoma

    Directory of Open Access Journals (Sweden)

    Xiang Lei

    2012-03-01

    Full Text Available Abstract Background Breast cancer is the most common cancer and the leading cause of cancer mortality in women worldwide. Hypoxia is an important factor involved in the progression of solid tumors and has been associated with various indicators of tumor metabolism, angiogenesis and metastasis. But little is known about the contribution of Hypoxia-Inducible Factor-2a (HIF-2a to the drug resistance and the clinicopathological characteristics in breast cancer. Methods Immunohistochemistry was employed on the tissue microarray paraffin sections of surgically removed samples from 196 invasive breast cancer patients with clinicopathological data. The correlations between the expression of HIF-2a and ABCG2 as well as other patients' clinicopathological data were investigated. Results The results showed that HIF-2a was expressed in different intensities and distributions in the tumor cells of the breast invasive ductal carcinoma. A positive staining for HIF-2a was defined as a brown staining observed mainly in the nucleus. A statistically significant correlation was demonstrated between HIF-2a expression and ABCG2 expression (p = 0.001, histology-grade (p = 0.029, and Ki67 (p = 0. 043 respectively. Conclusion HIF-2a was correlated with ABCG2 expression, histology-grade and Ki67 expression in breast invasive ductal carcinoma. HIF-2a could regulate ABCG2 in breast cancer cells, and could be a novel potential bio-marker to predict chemotherapy effectiveness. The hypoxia/HIF-2a/ABCG2 pathway could be a new mechanism of breast cancer multidrug-resistance. Virtual slides http://www.diagnosticpathology.diagnomx.eu/vs/2965948166714795

  6. Bilateral invasive lobular breast cancer in a female teenager: A rare ...

    African Journals Online (AJOL)

    Management of cancer patients in low-resource communities presents enormous challenges. Breast cancer is a public health problem in Cameroon and occurs mostly in elderly women. The predominant histological type is a duct carcinoma. Lobular carcinoma in teenagers is rare. In this report we present a case of bilateral ...

  7. Percutaneous Needle Biopsies of the Breast in Women Younger than 35 Years: Minimally or Excessively Invasive?

    Science.gov (United States)

    Abou-Zamzam, Aida; Somers, Scott; Cora, Cherie; Pairawan, Seyed; Lum, Sharon

    2017-10-01

    Percutaneous needle biopsy (PNB) of the breast is commonly used for diagnosis of breast pathology, but has been less studied in young women. We sought to determine the effectiveness and necessity of PNB in patients younger than 35 years of age. The charts of sequential patients BIRADS) ≥4 in 137 (75.7%) cases, with mass on imaging in 139 (76.8%). Carcinoma was diagnosed in 12 (6.6%), PNB in eight unique patients (6.3%). Other PNB pathology included atypia in four (2.2%) patients; papillary lesion, five (2.8%); benign lymph node, 10 (5.5%); fibroepithelial lesion, 15 (8.3%); benign breast tissue, 63 (34.8%); and fibroadenoma, 72 (39.8%). Women with atypia or malignancy were older than those with benign findings (30.9 vs 28.0 years, P = 0.002). No other patient or imaging factors were significantly associated with pathologic diagnosis on PNB. Routine PNB for all BIRADS 4 findings may be over-used in young women as most results are benign and subsequent surgical findings are concordant. Improved diagnostic accuracy of breast imaging is warranted to reduce unnecessary procedures.

  8. Large core biopsy for diagnostic and prognostic evaluation of invasive breast carcinomas.

    Science.gov (United States)

    Di Loreto, C; Puglisi, F; Rimondi, G; Zuiani, C; Anania, G; Della Mea, V; Beltrami, C A

    1996-09-01

    Large core biopsy is a recently introduced method for pre-operative evaluation of breast lumps. The aim of this study was to evaluate the usefulness of this technique in providing pre-operative diagnostic and prognostic information that can lead to a correct line of treatment. We compared 41 cases of breast carcinomas diagnosed both by core biopsies and surgically removed samples. A high (93%) diagnostic agreement was obtained. Moreover, we found a significant correlation for mitotic count (r = 0.76), oestrogen receptor (r = 0.78), progesterone receptor (r = 0.80), p53 (r = 0.86) and c-erbB-2 (r = 0.90) analysis between core biopsy and definitive surgical pathology. An agreement for histological grading evaluation between the two techniques was obtained in 32 out of 40 cases (k = 0.65) whereas in the other cases, a lower grade was assigned by evaluating core biopsies. These findings suggest that percutaneous core breast biopsy is a valid tool for pre-operative management of breast lesions, but this should be confirmed in larger, prospective studies.

  9. Recurrent phyllodes sarcoma of breast with complete chest wall invasion; a multidisciplinary approach for radical resection.

    Science.gov (United States)

    Chaudhry, Ikram Ulhaq; Asban, Ammar; Mahboub, Tarek; Arini, Ali

    2013-02-19

    Phyllodes tumour of the breast is a relatively uncommon condition, and rarely invades the chest wall. We report a case of young women who had recurrent large phyllodes tumour invading the chest wall, following mastectomy, chemotherapy and radiotherapy. A multidisciplinary approach was used for radical resection of the tumour, chest wall and reconstruction.

  10. Recurrent phyllodes sarcoma of breast with complete chest wall invasion; a multidisciplinary approach for radical resection

    OpenAIRE

    Chaudhry, Ikram Ulhaq; Asban, Ammar; Mahboub, Tarek; Arini, Ali

    2013-01-01

    Phyllodes tumour of the breast is a relatively uncommon condition, and rarely invades the chest wall. We report a case of young women who had recurrent large phyllodes tumour invading the chest wall, following mastectomy, chemotherapy and radiotherapy. A multidisciplinary approach was used for radical resection of the tumour, chest wall and reconstruction.

  11. 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

  12. Clinicopathologic features of sentinel node metastases predictive of positive axillary clearance in grade 1 invasive breast carcinoma.

    LENUS (Irish Health Repository)

    Hayes, B

    2012-02-01

    BACKGROUND: Sentinel node (SN) biopsy is widely used to stage breast carcinoma and, when positive, typically leads to axillary clearance (AC). AIMS: This study assesses clinicopathologic features of grade 1 breast carcinoma SNs with the aim of identifying a group of patients, who are likely to have a negative AC and can, therefore, safely be spared further surgery. RESULTS: Two hundred and forty-seven patients with grade 1 invasive carcinoma were identified, of whom 29 had a positive SN. Four patients (13.8%) had a positive AC. Positive AC occurred in 3 of 6 (50%) patients whose SN showed extranodal extension (EE), but in only 1 of 23 (4.3%) patients without EE. All patients were staged as pN1(sn) following SN biopsy: only one, who had a 5.27 mm metastasis with EE, was pN2 following AC. CONCLUSIONS: Extranodal extension is a significant predictor of a positive AC in this group. In its absence, AC did not alter the post-SN biopsy pN stage.

  13. miR-424-5p regulates cell proliferation, migration and invasion by targeting doublecortin-like kinase 1 in basal-like breast cancer.

    Science.gov (United States)

    Wang, Jianling; Wang, Shibing; Zhou, Jijun; Qian, Qian

    2018-03-15

    Our previous study has showed doublecortin like kinase 1 (DCLK1) serves as an oncogene to regulate basal-like breast cancer cell proliferation, migration and invasion, and is associated with malignant status and poor prognosis. The aim of this study is to identify microRNAs (miRNAs), which target DCLK1 to regulate basal-like breast cancer cell proliferation, migration and invasion. In our results, we observed that miR-424-5p expression was decreased in basal-like breast cancer tissues and cell lines. Furthermore, we found 3'-UTR of DCLK1 had binding site of miR-424-5p based on microRNA target databases, and there was an inverse correlation between miR-424-5p and DCLK1 in basal-like breast cancer tissues. Moreover, we confirmed miR-424-5p directly targeted to 3'-UTR of DCLK1 through luciferase reporter assay, and miR-424-5p negatively regulated DCLK1 mRNA and protein expressions through qRT-PCR and western blot. The gain-of-function studies showed that miR-424-5p suppressed basal-like breast cancer cell proliferation, migration and invasion. The rescued-function studies suggested up-regulation of DCLK1 could rescue inhibition of miR-424-5p mimics in the regulation of basal-like breast cancer cell proliferation, migration and invasion. Finally, low-expression of miR-424-5p was associated with advanced clinical stage, large tumor size, more metastatic lymph nodes, present distant metastasis and poor histological grade in basal-like breast cancer patients. In conclusion, miR-424-5p is a tumor suppressive microRNA to regulate tumor cell proliferation, migration and invasion via binding to the functional target DCLK1, and associated with malignant status in basal-like breast cancer. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  14. X-linked inhibitor of apoptosis positive nuclear labeling: a new independent prognostic biomarker of breast invasive ductal carcinoma

    Directory of Open Access Journals (Sweden)

    Peng Bofang

    2011-06-01

    Full Text Available Abstract Background It's well recognized that X-linked inhibitor of apoptosis (XIAP was the most potent caspase inhibitor and second mitochondria-derived activator of caspase (Smac was the antagonist of XIAP. Experiments in vitro identified that down regulation of XIAP expression or applying Smac mimics could sensitize breast cancer cells to chemotherapeutics and promote apoptosis. However, expression status and biologic or prognostic significance of XIAP/Smac in breast invasive ductal carcinoma (IDC were not clear. The present study aimed to investigate relationship among expression status of XIAP/Smac, apoptosis index (AI, clinicopathologic parameters and prognosis in IDC. Methods Immunohistochemistry and TUNEL experiment were performed to detect expression of XIAP, Smac, ER, PR, HER2 and AI in 102 cases of paraffin-embedded IDC samples respectively. Expression of XIAP/Smac were also detected in limited 8 cases of fresh IDC specimens with Western blot. Results Positive ratio and immunoscore of XIAP was markedly higher than Smac in IDC (P P s = 0.265, P = 0.017. The present study first revealed that XIAP positive nuclear labeling (XIAP-N, but not cytoplasmic staining (XIAP-C, was the apoptotic marker correlated significantly with patients' shortened overall survival (P = 0.039. Survival analysis demonstrated that XIAP-N was a new independent prognostic factor except for patient age and lymph node status. Conclusion Disturbed balance of expression between XIAP and Smac probably contributed to carcinogenesis and XIAP positive nuclear labeling was a new independent prognostic biomarker of breast IDC.

  15. Prospective MRI assessment for invasive lobular breast cancer. Correlation with tumour size at histopathology and influence on surgical management

    International Nuclear Information System (INIS)

    Muttalib, M.; Ibrahem, R.; Khashan, A.S.; Hajaj, M.

    2014-01-01

    Aim: To evaluate the performance of breast magnetic resonance imaging (MRI) in determining the size of invasive lobular carcinoma (ILC) compared to histopathology, and its influence on breast surgical management. Materials and methods: Prospective evaluation was undertaken of standardized contrast-enhanced MRI images of 51 consecutive women over an 18 month period with pure ILC or with lobular features as the dominant subtype on breast core biopsy. Image interpretation was performed by one consultant radiologist (M.H.). The lesion size at MRI was compared with the size at final histopathology after surgical excision using a Bland–Altman agreement plot. Results: Of the 51 prospectively imaged consecutive women, seven were excluded as they had diffuse ILC. The remaining 44 patients had a mean histological tumour size of 34.9 mm (range 4–77 mm). MRI underestimated tumour size in 26 (59.1%) cases. In 21 (47.7%) patients, this discrepancy was small, ranging up to 16 mm. The largest underestimation occurred in five (11.4%) cases with a difference ranging between 31 and 48 mm. Fifteen (34.1%) tumours were overestimated by MRI where the discrepancy ranged up to 22 mm. In three (6.8%) patients MRI and histological size matched. The Bland–Altman agreement plot demonstrated that in 95% of cases the size at histopathology will be between 0.36 and 2.31 times the MRI size at extremes. MRI correlated better with histopathology in tumours up to T2 (<5 cm) size leading to a change in surgical management for nine of the 44 (20.5%) patients. Conclusion: MRI enables surgical management decisions to be made with increased confidence in patients with ILC up to T2 size

  16. Added Value of HER-2 Amplification Testing by Multiplex Ligation-Dependent Probe Amplification in Invasive Breast Cancer

    Science.gov (United States)

    Kuijpers, Chantal C. H. J.; Moelans, Cathy B.; van Slooten, Henk-Jan; Horstman, Anja; Hinrichs, John W. J.; Al-Janabi, Shaimaa; van Diest, Paul J.; Jiwa, Mehdi

    2013-01-01

    Background HER-2 is a prognostic and predictive marker, but as yet no technique is perfectly able to identify patients likely to benefit from HER-2 targeted therapies. We aimed to prospectively assess the added value of first-line co-testing by IHC, and multiplex ligation-dependent probe amplification (MLPA) and chromogenic in situ hybridization (CISH). Methods As local validation, HER-2 MLPA and CISH were compared in 99 breast cancers. Next, we reviewed 937 invasive breast cancers, from 4 Dutch pathology laboratories, that were prospectively assessed for HER-2 by IHC and MLPA (and CISH in selected cases). Results The validation study demonstrated 100% concordance between CISH and MLPA, if both methods were assessable and conclusive (81.8% of cases). Significant variation regarding percentages IHC 0/1+ and 2+ cases was observed between the laboratories (pCISH was 98.1% (575/586) (Kappa = 0.94). Of the IHC 3+ cases, 6.7% failed to reveal gene amplification, whereas 0.8% of the IHC 0/1+ cases demonstrated gene amplification. Results remained discordant after retrospective review in 3/11 discordant cases. In the remaining 8 cases the original IHC score was incorrect or adapted after repeated IHC staining. Conclusions MLPA is a low-cost and quantitative high-throughput technique with near perfect concordance with CISH. The use of MLPA in routinely co-testing all breast cancers may reduce HER-2 testing variation between laboratories, may serve as quality control for IHC, will reveal IHC 0/1+ patients with gene amplification, likely responsive to trastuzumab, and identify IHC 3+ cases without gene amplification that may respond less well. PMID:24324739

  17. Added value of HER-2 amplification testing by multiplex ligation-dependent probe amplification in invasive breast cancer.

    Directory of Open Access Journals (Sweden)

    Chantal C H J Kuijpers

    Full Text Available BACKGROUND: HER-2 is a prognostic and predictive marker, but as yet no technique is perfectly able to identify patients likely to benefit from HER-2 targeted therapies. We aimed to prospectively assess the added value of first-line co-testing by IHC, and multiplex ligation-dependent probe amplification (MLPA and chromogenic in situ hybridization (CISH. METHODS: As local validation, HER-2 MLPA and CISH were compared in 99 breast cancers. Next, we reviewed 937 invasive breast cancers, from 4 Dutch pathology laboratories, that were prospectively assessed for HER-2 by IHC and MLPA (and CISH in selected cases. RESULTS: The validation study demonstrated 100% concordance between CISH and MLPA, if both methods were assessable and conclusive (81.8% of cases. Significant variation regarding percentages IHC 0/1+ and 2+ cases was observed between the laboratories (p<0.0001. Overall concordance between IHC and MLPA/CISH was 98.1% (575/586 (Kappa = 0.94. Of the IHC 3+ cases, 6.7% failed to reveal gene amplification, whereas 0.8% of the IHC 0/1+ cases demonstrated gene amplification. Results remained discordant after retrospective review in 3/11 discordant cases. In the remaining 8 cases the original IHC score was incorrect or adapted after repeated IHC staining. CONCLUSIONS: MLPA is a low-cost and quantitative high-throughput technique with near perfect concordance with CISH. The use of MLPA in routinely co-testing all breast cancers may reduce HER-2 testing variation between laboratories, may serve as quality control for IHC, will reveal IHC 0/1+ patients with gene amplification, likely responsive to trastuzumab, and identify IHC 3+ cases without gene amplification that may respond less well.

  18. Distribution of myofibroblast cells and microvessels around invasive ductal carcinoma of the breast and comparing with the adjacent range of their normal-to-DCIS zones.

    Science.gov (United States)

    Dabiri, Shahriar; Talebi, Amin; Shahryari, Jahanbanoo; Meymandi, Manzoumeh Shamsi; Safizadeh, Hossein

    2013-02-01

    This study seeks to determine the relationships between manifestation of myofibroblasts in the stroma tissue of hyperplastic pre-invasive breast lesions to invasive cancer by investigating clinicopathological data of patients, their effect on steroid receptor expression and HER2, and angiogenesis according to CD34 antigen expression. 100 cases of invasive ductal carcinoma were immunohistochemically investigated for the presence of smooth muscle actin (SMA), ER/PR, HER2, anti-CD34 antibody and microvessel count (MVC). Patients were scored in four different zones of invasive areas: invasive cancer, DCIS, fibrocystic disease ± ductal intraepithelial neoplasia (FCD ± DIN), and normal tissue.  There was a significant difference in stromal myofibroblasts between all areas except for the stroma of DCIS and FCD ± DIN (P normal areas (P = 0.054). There was a significant difference in MVC observed in all areas except for DCIS and FCD ± DIN (P < 0.001). We noted significant inverse correlations between MVC, HER2 expression, and the numbers of involved lymph nodes in invasive cancer and DCIS (P < 0.001). Most MVC were present in grade I, with the least frequent observed in grade III cases in the stroma of invasive cancer, DCIS and FCD ± DIN (P < 0.001).  Angiogenesis can be observed before any significant myofibroblastic changes in the pre-invasive breast lesions. The elevated content of myofibroblasts in stroma of tumor; probably may be a worse prognostic factor  and the steps from atypical epithelial hyperplasia to DCIS and then to the invasive carcinoma do not appear to be always part of a linear progression.

  19. 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.

  20. Bilateral Invasive Lobular Breast Carcinoma in a Young Woman: Case Report

    International Nuclear Information System (INIS)

    Abella Calle, Jose; Valenzuela Gallego, Marcela

    2012-01-01

    The histopathological and clinical features of invasive lobular carcinoma (ILCs) are responsible for its varying imaging appearance; therefore, an adequate correlation between the different imaging modalities available aids in determining tumor extension and in identifying the number of lesions. This article presents the case of a young woman diagnosed with multiple and bilateral ILC with metastatic disease.

  1. Identification of Genetic Markers of the Invasive Phenotype in Human Breast Cancer

    Science.gov (United States)

    2000-10-01

    30 Al of probe per products of the two genes amplified from the same RT section) that had undergone postfixation with 4% para - reaction were loaded...group alone (n = 34, r = 0.39, P = 0.023). Cases with Expression of Psoriasin-mRNA in Invasive Western blot-detectable psoriasi [rp-rotein also showed

  2. ERβ1 inhibits the migration and invasion of breast cancer cells through upregulation of E-cadherin in a Id1-dependent manner

    International Nuclear Information System (INIS)

    Zhou, Yan; Ming, Jia; Xu, Yan; Zhang, Yi; Jiang, Jun

    2015-01-01

    Highlights: • Expression of ERβ1 was positively correlated with E-cadherin in breast cancer cell. • ERβ1 upregulates E-cadherin expression in breast cancer cell lines. • ERβ1 upregulates E-cadherin expression in a Id1-dependent manner. - Abstract: ERβ1 is a member of the nuclear receptor superfamily of ligand-regulated transcription factors. It plays an important role in regulating the progression of breast cancer. However, the mechanisms of ERβ1 in tumorigenesis, metastasis and prognosis are still not fully clear. In this study, we showed that the expression of ERβ1 was positively correlated with E-cadherin expression in breast cancer cell lines. In addition, we found that ERβ1 upregulates E-cadherin expression in breast cancer cell lines. Furthermore, we also found that ERβ1 inhibits the migration and invasion of breast cancer cells and upregulated E-cadherin expression in a Id1-dependent manner. Taken together, our study provides further understanding of the molecular mechanism of ERβ1 in tumor metastasis and suggests the feasibility of developing novel therapeutic approaches to target Id1 to inhibit breast cancer metastasis

  3. ERβ1 inhibits the migration and invasion of breast cancer cells through upregulation of E-cadherin in a Id1-dependent manner

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Yan [Breast Disease Center, Southwest Hospital, Third Military Medical University, Chongqing (China); Ming, Jia [Department of Breast, Thyroid and Pancreas Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing (China); Xu, Yan [Department of Breast and Thyroid Surgery, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing (China); Zhang, Yi, E-mail: zy53810@163.com [Breast Disease Center, Southwest Hospital, Third Military Medical University, Chongqing (China); Jiang, Jun, E-mail: Jcbd@medmail.com.cn [Breast Disease Center, Southwest Hospital, Third Military Medical University, Chongqing (China)

    2015-02-06

    Highlights: • Expression of ERβ1 was positively correlated with E-cadherin in breast cancer cell. • ERβ1 upregulates E-cadherin expression in breast cancer cell lines. • ERβ1 upregulates E-cadherin expression in a Id1-dependent manner. - Abstract: ERβ1 is a member of the nuclear receptor superfamily of ligand-regulated transcription factors. It plays an important role in regulating the progression of breast cancer. However, the mechanisms of ERβ1 in tumorigenesis, metastasis and prognosis are still not fully clear. In this study, we showed that the expression of ERβ1 was positively correlated with E-cadherin expression in breast cancer cell lines. In addition, we found that ERβ1 upregulates E-cadherin expression in breast cancer cell lines. Furthermore, we also found that ERβ1 inhibits the migration and invasion of breast cancer cells and upregulated E-cadherin expression in a Id1-dependent manner. Taken together, our study provides further understanding of the molecular mechanism of ERβ1 in tumor metastasis and suggests the feasibility of developing novel therapeutic approaches to target Id1 to inhibit breast cancer metastasis.

  4. Stroke due to non-bacterial thrombotic endocarditis as initial presentation of breast invasive ductal carcinoma.

    Science.gov (United States)

    Detremerie, Celine; Timmermans, Frank; De Pauw, Michel; Gheeraert, Peter; Hemelsoet, Dimitri; Toeback, Jonas; Bové, Thierry; Vandecasteele, Els

    2017-08-01

    We present a case of a 71-year-old woman with recurrent stroke episodes due to non-bacterial thrombotic endocarditis (NBTE) leading to the diagnosis of an early-stage breast carcinoma. NBTE is associated with a variety of inflammatory states, including malignancy. NBTE presents itself with systemic embolization, mostly stroke. Treatment consists of treating the underlying condition and start of systemic anticoagulation therapy. Cardiac surgery is restricted to highly selected cases, since prognosis usually is limited by the neoplasm, which usually is in an advanced stage at time of diagnosis of NBTE. The malignancy usually is diagnosed prior to NBTE. Cases presenting with NBTE leading to the diagnosis of malignancy, however, are rarely reported. To our knowledge, we present the first case leading to the diagnosis of an early-stage breast carcinoma.

  5. Prolactin receptor attenuation induces zinc pool redistribution through ZnT2 and decreases invasion in MDA-MB-453 breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Bostanci, Zeynep, E-mail: zbostanci@hmc.psu.edu [The Pennsylvania State University, Department of Nutritional Sciences, 209 Chandlee Lab, University Park, PA 16802 (United States); The Pennsylvania State University Milton S. Hershey Medical Center, Department of Surgery, 500 University Dr., Hershey, PA 17033 (United States); Alam, Samina, E-mail: sra116@psu.edu [The Pennsylvania State University, Department of Nutritional Sciences, 209 Chandlee Lab, University Park, PA 16802 (United States); The Pennsylvania State University Milton S. Hershey Medical Center, Department of Surgery, 500 University Dr., Hershey, PA 17033 (United States); Soybel, David I., E-mail: dsoybel@hmc.psu.edu [The Pennsylvania State University, Department of Nutritional Sciences, 209 Chandlee Lab, University Park, PA 16802 (United States); The Pennsylvania State University Milton S. Hershey Medical Center, Department of Surgery, 500 University Dr., Hershey, PA 17033 (United States); The Pennsylvania State University College of Medicine, Department of Cell and Molecular Physiology, 500 University Dr., Hershey, PA 17033 (United States); Kelleher, Shannon L., E-mail: slk39@psu.edu [The Pennsylvania State University, Department of Nutritional Sciences, 209 Chandlee Lab, University Park, PA 16802 (United States); The Pennsylvania State University Milton S. Hershey Medical Center, Department of Surgery, 500 University Dr., Hershey, PA 17033 (United States); The Pennsylvania State University College of Medicine, Department of Cell and Molecular Physiology, 500 University Dr., Hershey, PA 17033 (United States)

    2014-02-15

    Prolactin receptor (PRL-R) activation regulates cell differentiation, proliferation, cell survival and motility of breast cells. Prolactin (PRL) and PRL-R over-expression are strongly implicated in breast cancer, particularly contributing to tumor growth and invasion in the more aggressive estrogen-receptor negative (ER−) disease. PRL-R antagonists have been suggested as potential therapeutic agents; however, mechanisms through which PRL-R antagonists exert their actions are not well-understood. Zinc (Zn) is a regulatory factor for over 10% of the proteome, regulating critical cell processes such as proliferation, cell signaling, transcription, apoptosis and autophagy. PRL-R signaling regulates Zn metabolism in breast cells. Herein we determined effects of PRL-R attenuation on cellular Zn metabolism and cell function in a model of ER-, PRL-R over-expressing breast cancer cells (MDA-MB-453). PRL-R attenuation post-transcriptionally increased ZnT2 abundance and redistributed intracellular Zn pools into lysosomes and mitochondria. ZnT2-mediated lysosomal Zn sequestration was associated with reduced matrix metalloproteinase 2 (MMP-2) activity and decreased invasion. ZnT2-mediated Zn accumulation in mitochondria was associated with increased mitochondrial oxidation. Our results suggest that PRL-R antagonism in PRL-R over-expressing breast cancer cells may reduce invasion through the redistribution of intracellular Zn pools critical for cellular function. - Highlights: • PRL-R attenuation increased ZnT2 expression. • PRL-R attenuation increased lysosomal and mitochondrial Zn accumulation. • PRL-R attenuation decreased MMP-2 and invasion. • PRL-R antagonists may modulate lysosomal and mitochondrial Zn pools.

  6. New insight into Ki67 expression at the invasive front in breast cancer.

    Science.gov (United States)

    Gong, Peng; Wang, Yingxin; Liu, Gavin; Zhang, Jing; Wang, Zhongyu

    2013-01-01

    To investigate the distribution of Ki67+ cells in breast cancer in relation to clinical-pathological parameters and prognosis. Ki67 expression status was detected in 1,086 breast cancer specimens using immunohistochemistry staining and examining the relationship between the Ki67+ cells' location. Subsequently, clinical-pathological parameters and prognosis were determined. In total, Ki67 protein expression was found in 781 (71.92%) of the 1,086 breast cancer specimens. Among the 781 Ki67+ cases, 461 were defined as diffuse type and 320 were defined as borderline type. After universal correlation analysis, significant differences were observed in age, histological grade, metastatic nodes, postoperative distant metastasis, and molecular subtype between Ki67+ and Ki67- cases (P = 0.01, 0.001, 0.001, 0.001, and 0.001, respectively). After subgroup analysis, the borderline cases were found to be characterized by a high distant metastasis rate compared to the diffuse cases as well as the Ki67- cases (P = 0.001). No differences were observed between diffuse type or Ki67- cases (P = 0.105). Multivariate analysis showed that age, tumor size, histological grade, lymph node metastasis, molecular subtype, and the Ki67 distribution pattern were observed to be related to postoperative distant metastasis (all PKi67 distribution pattern was detected as an independent prognostic factor (P = 0.001). The distribution pattern of Ki67 may be a new independent prognostic factor for breast cancer.

  7. New insight into Ki67 expression at the invasive front in breast cancer.

    Directory of Open Access Journals (Sweden)

    Peng Gong

    Full Text Available PURPOSE: To investigate the distribution of Ki67+ cells in breast cancer in relation to clinical-pathological parameters and prognosis. MATERIALS AND METHODS: Ki67 expression status was detected in 1,086 breast cancer specimens using immunohistochemistry staining and examining the relationship between the Ki67+ cells' location. Subsequently, clinical-pathological parameters and prognosis were determined. RESULTS: In total, Ki67 protein expression was found in 781 (71.92% of the 1,086 breast cancer specimens. Among the 781 Ki67+ cases, 461 were defined as diffuse type and 320 were defined as borderline type. After universal correlation analysis, significant differences were observed in age, histological grade, metastatic nodes, postoperative distant metastasis, and molecular subtype between Ki67+ and Ki67- cases (P = 0.01, 0.001, 0.001, 0.001, and 0.001, respectively. After subgroup analysis, the borderline cases were found to be characterized by a high distant metastasis rate compared to the diffuse cases as well as the Ki67- cases (P = 0.001. No differences were observed between diffuse type or Ki67- cases (P = 0.105. Multivariate analysis showed that age, tumor size, histological grade, lymph node metastasis, molecular subtype, and the Ki67 distribution pattern were observed to be related to postoperative distant metastasis (all P<0.05. Furthermore, borderline type was shown to attain a significantly more distant bone and liver metastasis and worse disease-specific survival than the other types (P = 0.001. In the Cox regression test, the Ki67 distribution pattern was detected as an independent prognostic factor (P = 0.001. CONCLUSION: The distribution pattern of Ki67 may be a new independent prognostic factor for breast cancer.

  8. A Unique Case of Muscle Invasive Metastatic Breast Cancer Mimicking Myositis

    Science.gov (United States)

    2017-06-28

    of non-Hispanic white women, diagnosis of metastatic disease as the initial presentation is seen in 6% of patients (1). Breast cancer typically...of widely disseminated disease [3, 4). Extra nodal head and neck metastases are also uncommon with only a few case reports and case series documenting...involvement of the thyroid , mandible, subcutaneous tissues, or pharynx [S- 11]. Thus, metastases to muscles of the neck are almost unheard of, w ith

  9. The Effect of Coexistence of a Pair of Mutated Oncogenes on the Survival Rate of Invasive Breast Carcinoma Patients

    Science.gov (United States)

    Nair, D. R.

    2017-12-01

    The purpose of this project was to determine the effect of two mutated oncogenes on the survival rate from invasive breast carcinoma when in comparison to the mutation of a single oncogene on the survival rate. An oncogene is defined as a gene, that when mutated, can lead to cancer. The two oncogenes used in this project were human epidermal growth factor receptor 2 (HER2) and c-myc (MYC). HER2 and MYC are both oncogenes that contribute to the formation of cancer. HER2 proteins are receptors on breast cells, and when the HER2 gene is mutated, there is an overexpre