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Sample records for breast cancer invasion

  1. Magnetic resonance imaging of invasive breast cancer

    African Journals Online (AJOL)

    G5

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

  2. 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.

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

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

    2014-08-11

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

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

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    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.

  5. 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.

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

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

    2006-01-01

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

  7. Epitrochlear lymph node metastases from invasive ductal breast cancer

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    Kumar Pavan

    2009-01-01

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

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

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

    2012-06-13

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

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

    Directory of Open Access Journals (Sweden)

    Vermeulen Jeroen F

    2012-06-01

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

  10. 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.

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

    OpenAIRE

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

    2011-01-01

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

  12. 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

  13. Comprehensive molecular portraits of invasive lobular breast cancer

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

    2015-01-01

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

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

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

    2015-12-01

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

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

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

    2014-03-01

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

  16. 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.

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

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

    2017-12-01

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

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

    Science.gov (United States)

    2016-09-01

    epigenetic alterations of pre-invasive DCIS that did or did not progress to invasive breast cancer, with an in-depth...NIH- funded study of genetic and epigenetic alterations of pre-invasive DCIS that either progressed to invasive breast cancer IBC (cases) or had no...Hill, NC 27599 8. Special Reporting Requirements N/A 9. Appendices 19 References 1. R-Core-Team: R: A language and environment

  19. SMARCAD1 knockdown uncovers its role in breast cancer cell migration, invasion, and metastasis.

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    Al Kubaisy, Elham; Arafat, Kholoud; De Wever, Olivier; Hassan, Ahmed H; Attoub, Samir

    2016-09-01

    Breast cancer is the most common cancer seen in women worldwide and breast cancer patients are at high risk of recurrence in the form of metastatic disease. Identification of genes associated with invasion and metastasis is crucial in order to develop novel anti-metastasis targeted therapy. It has been demonstrated that the DEAD-BOX helicase DP103 was implicated in breast cancer invasion and metastasis. SMARCAD1 is also a DEAD/H box-containing helicase, suggested to play a role in genetic instability. However, its involvement in cancer migration, invasion, and metastasis has never been explored. Using two different designs of shRNA targeting SMARCAD1, we investigated the impact of SMARCAD1 knockdown on the migration, invasion, and metastasis potential of the breast cancer cells MDA-MB-231 and T47D. We observed that SMARCAD1 knockdown in the invasive breast cancer cells MDA-MB-231, unlike in the non-invasive breast cancer cells T47D, was associated with an increased cell-cell adhesion and a significant decrease in cell migration, invasion, and metastasis due at least in part to a strong inhibition of STAT3 phosphorylation. These results indicate that SMARCAD1 is involved in breast cancer metastasis and can be a promising target for metastatic breast cancer therapy.

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

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    Irmawati Hassan

    2015-12-01

    The study showed that invasive ductal breast cancer with high Ki-67 index was significantly associated with high grade of malignacy. The high Ki-67 marker index can be used for classification of the grade of malignancy of invasive ductal breast cancer.

  1. 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

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

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    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

  3. Delayed breast reconstruction with implants after invasive breast cancer does not impair prognosis

    DEFF Research Database (Denmark)

    Holmich, L.R.; During, M.; Henriksen, T.F.

    2008-01-01

    We investigated if delayed breast implant reconstruction after breast cancer impairs prognosis. Using data from the Danish Breast Cancer Cooperative Group register, we identified all women......We investigated if delayed breast implant reconstruction after breast cancer impairs prognosis. Using data from the Danish Breast Cancer Cooperative Group register, we identified all women...

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

    NARCIS (Netherlands)

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

    2012-01-01

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

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

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

    2016-01-28

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

  6. Elasticity, adhesion and tether extrusion on breast cancer cells provide a signature of their invasive potential.

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    Smolyakov, Georges; Thiebot, Bénédicte; Campillo, Clément C; Labdi, Sid; Séverac, Childérick; Pelta, Juan; Dague, Etienne

    2016-10-05

    We use single cell force spectroscopy to compare elasticity, adhesion and tether extrusion on four breast cancer cell lines with an increasing invasive potential. We perform cell attachment/detachment experiments either on fibronectin or on another cell using an Atomic Force Microscope. Our study on the membrane tether formation from cancer cells show that they are easier to extrude from aggressive invasive cells. Measured elastic modulus values confirm that more invasive cells are softer. Moreover, the adhesion force increases with the invasive potential. Our results provide a mechanical signature of breast cancer cells that correlates with their invasivity.

  7. Upregulation of MEK5 by Stat3 promotes breast cancer cell invasion and metastasis.

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    Liu, Fang; Zhang, Hao; Song, Hui

    2017-01-01

    Mitogen extracellular-signal-regulated kinase kinase 5 (MEK5) plays an important role in promoting cell proliferation and tumorigenesis. The aberrant expression of MEK5 has been reported in various malignant diseases including cancers of breast, prostate, lung, colorectal and brain. However, the function and regulation of MEK5 signaling pathway are ambiguous and remain elusive with respect to its oncogenic roles in various cancers, especially in the regulation of the initiation and progression of cancer invasion and metastasis. Ectopic expression of MEK5 or knockdown of MEK5 by shRNA with in vitro cell based models demonstrated the role of MEK5 in regulation of epithelial mesenchymal transition (EMT) and breast cancer invasion and metastasis. Here, we show that MEK5 upregulated by Stat3 promotes breast cancer cell invasion through EMT. Further study demonstrated that Stat3 could bind to promoter region of MEK5 and enhanced MEK5 transcription and expression. In addition, the phosphorylation of MEK5 significantly increased in breast cancer cells corresponding to metastatic capability of breast cancer cells. The depletion of MEK5 by shRNA significantly decreased breast cancer invasion. Ectopic expression of MEK5 could confer non-invasive breast cancer cells to become invasion capable cells. Moreover, the phosphorylation of Erk5, a MEK5-regulated downstream kinase, was also upregulated consistent with the increased level of active MEK5. Our studies provide insights into a molecular mechanism by which MEK5 transcriptionally upregulated by Stat3 augments breast cancer cell EMT, which subsequently enhances cancer cell invasion and metastasis. This finding may suggest that Stat3 and MEK5/Erk5 pathways could be an effective therapeutic target for inhibition of breast cancer invasion and metastasis.

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

    Science.gov (United States)

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

    2017-02-01

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

  9. 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.

  10. 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.

  11. 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

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

    Science.gov (United States)

    Vogel, Victor G

    2008-01-01

    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. PMID:19281053

  13. Patient Preferences for Minimally Invasive and Open Locoregional Treatment for Early-Stage Breast Cancer

    NARCIS (Netherlands)

    Knuttel, Floor; van den Bosch, Maurice A A J|info:eu-repo/dai/nl/182981630; Young-Afat, Danny A.; Emaus, Marleen J.; van den Bongard, Desirée H J G; Witkamp, Arjen J.|info:eu-repo/dai/nl/245008780; Verkooijen, Helena M.|info:eu-repo/dai/nl/213707705

    Background: Noninvasive or minimally invasive treatments are being developed as alternatives to surgery for patients with early-stage breast cancer. Patients' preferences with regard to these new treatments have not been investigated. Objectives: To assess preferences of patients with breast cancer

  14. 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

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

    Science.gov (United States)

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

    2009-07-29

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

  16. 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.

  17. Administrative data algorithms to identify second breast cancer events following early-stage invasive breast cancer.

    Science.gov (United States)

    Chubak, Jessica; Yu, Onchee; Pocobelli, Gaia; Lamerato, Lois; Webster, Joe; Prout, Marianne N; Ulcickas Yood, Marianne; Barlow, William E; Buist, Diana S M

    2012-06-20

    Studies of breast cancer outcomes rely on the identification of second breast cancer events (recurrences and second breast primary tumors). Cancer registries often do not capture recurrences, and chart abstraction can be infeasible or expensive. An alternative is using administrative health-care data to identify second breast cancer events; however, these algorithms must be validated against a gold standard. We developed algorithms using data from 3152 women in an integrated health-care system who were diagnosed with stage I or II breast cancer in 1993-2006. Medical record review served as the gold standard for second breast cancer events. Administrative data used in algorithm development included procedures, diagnoses, prescription fills, and cancer registry records. We randomly divided the cohort into training and testing samples and used a classification and regression tree analysis to build algorithms for classifying women as having or not having a second breast cancer event. We created several algorithms for researchers to use based on the relative importance of sensitivity, specificity, and positive predictive value (PPV) in future studies. The algorithm with high specificity and PPV had 89% sensitivity (95% confidence interval [CI] = 84% to 92%), 99% specificity (95% CI = 98% to 99%), and 90% PPV (95% CI = 86% to 94%); the high-sensitivity algorithm had 96% sensitivity (95% CI = 93% to 98%), 95% specificity (95% CI = 94% to 96%), and 74% PPV (95% CI = 68% to 78%). Algorithms based on administrative data can identify second breast cancer events with high sensitivity, specificity, and PPV. The algorithms presented here promote efficient outcomes research, allowing researchers to prioritize sensitivity, specificity, or PPV in identifying second breast cancer events.

  18. A Unique Case of Muscle Invasive Metastatic Breast Cancer Mimicking Myositis

    Science.gov (United States)

    2017-06-28

    TYPE 08/ 03/20 17 Publ ication/Journal 4. TITLE AND SUBTITLE A unique case of muscle-invasive metastatic breast cancer mimicking myositis 6...Rev. 8/98) Prescnbed by ANSI Std Z39. 18 Adobe Profes11on11 7.0 Title: A Unique Case of M uscle-Invasive Metastatic Breast Cancer M imicking...an 84-year-old female who presented with neck swelling and upper airway obstruction due to metastatic breast cancer invading the sternocleidomastoid

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

    Directory of Open Access Journals (Sweden)

    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.

  20. 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

  1. 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.

  2. 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.

  3. 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.

  4. Parameter estimates for invasive breast cancer progression in the Canadian National Breast Screening Study.

    Science.gov (United States)

    Taghipour, S; Banjevic, D; Miller, A B; Montgomery, N; Jardine, A K S; Harvey, B J

    2013-02-19

    The aim of screening is to detect a cancer in the preclinical state. However, a false-positive or a false-negative test result is a real possibility. We describe invasive breast cancer progression in the Canadian National Breast Screening Study and construct progression models with and without covariates. The effect of risk factors on transition intensities and false-negative probability is investigated. We estimate the transition rates, the sojourn time and sensitivity of diagnostic tests for women aged 40-49 and 50-59. Although younger women have a slower transition rate from healthy state to preclinical, their screen-detected tumour becomes evident sooner. Women aged 50-59 have a higher mortality rate compared with younger women. The mean sojourn times for women aged 40-49 and 50-59 are 2.5 years (95% CI: 1.7, 3.8) and 3.0 years (95% CI: 2.1, 4.3), respectively. Sensitivity of diagnostic procedures for older women is estimated to be 0.75 (95% CI: 0.55, 0.88), while women aged 40-49 have a lower sensitivity (0.61, 95% CI: 0.42, 0.77). Age is the only factor that affects the false-negative probability. For women aged 40-49, 'age at entry', 'history of breast disease' and 'families with breast cancer' are found to be significant for some of the transition rates. For the age-group 50-59, 'age at entry', 'history of breast disease', 'menstruation length' and 'number of live births' are found to affect the transition rates. Modelling and estimating the parameters of cancer progression are essential steps towards evaluating the effectiveness of screening policies. The parameters include the transition rates, the preclinical sojourn time, the sensitivity, and the effect of different risk factors on cancer progression.

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

    Energy Technology Data Exchange (ETDEWEB)

    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

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

    Science.gov (United States)

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

    2017-12-01

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

  7. Treatment of osteoporosis and reduction in risk of invasive breast cancer in postmenopausal women with raloxifene

    Science.gov (United States)

    Ko, Seung Sang; Jordan, V Craig

    2011-01-01

    Introduction Raloxifene, a non-steroidal selective estrogen receptor modulator (SERM), offers a new dimension for the treatment and prevention of osteoporosis and risk reduction of invasive breast cancer in postmenopausal populations at high risk. Both osteoporosis and breast cancer are important public health issues for postmenopausal women. It is well known that estrogen and estrogen receptors play an important role in the pathogenesis of both diseases. Initially, hormone replacement therapy (HRT) was used for the purpose of preventing and treating postmenopausal osteoporosis. However, HRT significantly contributed to an increase in breast cancer risk. The SERM, raloxifene, is used for the prevention and for the treatment of post-menopausal osteoporosis and reducing the risk of invasive breast cancer in postmenopausal women. Areas covered This article reviews the emerging evidence of the efficacy of raloxifene in postmenopausal women, summarizes the results and places in perspective their therapeutic uses for women having either a high risk of osteoporosis or breast cancer. Emerging clinical evidence suggests bisphosphonates, currently used as drugs for the treatment of osteoporosis, may also reduce breast cancer risk. The status of other SERMs and bisphosphonates are included for completeness. A Medline search of raloxifene, osteoporosis, breast cancer and SERMs was used to derive a database of 355 references. Expert opinion Readers will understand the value of raloxifene to prevent osteoporosis and breast cancer in postmenopausal women. Although most women do not require pharmacotherapy for menopausal symptoms, many are severely affected by osteoporosis or breast cancer at and beyond menopause and, for such women, pharmacologic intervention is important if they are to retain an acceptable quality of life. It is reasonable to use raloxifene or bisphosphonate as an appropriate drug that targets symptom-free postmenopausal women for treatment and prevention of

  8. 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.

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

    Science.gov (United States)

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

    2016-01-01

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

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

    OpenAIRE

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

    2012-01-01

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

  11. 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.

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

    Science.gov (United States)

    Wang, Shouman; Chen, Feiyu; Tang, Lili

    2015-01-01

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

  13. 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...

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

    Science.gov (United States)

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

    2014-07-01

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

  15. Evaluation of carbonic anhydrase IX as a therapeutic target for inhibition of breast cancer invasion and metastasis using a series of in vitro breast cancer models.

    Science.gov (United States)

    Ward, Carol; Meehan, James; Mullen, Peter; Supuran, Claudiu; Dixon, J Michael; Thomas, Jeremy S; Winum, Jean-Yves; Lambin, Philippe; Dubois, Ludwig; Pavathaneni, Nanda-Kumar; Jarman, Edward J; Renshaw, Lorna; Um, In Hwa; Kay, Charlene; Harrison, David J; Kunkler, Ian H; Langdon, Simon P

    2015-09-22

    Triple negative, resistant or metastatic disease are major factors in breast cancer mortality, warranting novel approaches. Carbonic anhydrase IX (CAIX) is implicated in survival, migration and invasion of breast cancer cells and inhibition provides an innovative therapeutic strategy. The efficacy of 5 novel ureido-substituted sulfamate CAIX inhibitors were assessed in increasingly complex breast cancer models, including cell lines in normoxia and hypoxia, 3D spheroids and an ex-vivo explant model utilizing fresh biopsy tissue from different breast cancer subtypes. CAIX expression was evaluated in a tissue microarray (TMA) of 92 paired lymph node and primary breast cancers and 2 inhibitors were appraised in vivo using MDA-MB-231 xenografts. FC11409B, FC9398A, FC9403, FC9396A and S4 decreased cell proliferation and migration and inhibited 3D spheroid invasion. S4, FC9398A and FC9403A inhibited or prevented invasion into collagen. FC9403A significantly reversed established invasion whilst FC9398A and DTP348 reduced xenograft growth. TMA analysis showed increased CAIX expression in triple negative cancers. These data establish CAIX inhibition as a relevant therapeutic goal in breast cancer, targeting the migratory, invasive, and metastatic potential of this disease. The use of biopsy tissue suggests efficacy against breast cancer subtypes, and should provide a useful tool in drug testing against invasive cancers.

  16. Life expectancy of screen-detected invasive breast cancer patients compared with women invited to the Nijmegen Screening Program

    NARCIS (Netherlands)

    J.D.M. Otten; M.J.M. Broeders (Mireille); G.J. den Heeten (Gerard); R. Holland (Roland); J. Fracheboud (Jacques); H.J. de Koning (Harry); A.L.M. Verbeek (Andre)

    2010-01-01

    textabstractBACKGROUND: Screening can lead to earlier detection of breast cancer and thus to an improvement in survival. The authors studied the life expectancy of women with screen-detected invasive breast cancer (patients) compared with women invited to the breast cancer screening program in

  17. Life expectancy of screen-detected invasive breast cancer patients compared with women invited to the Nijmegen screening program

    NARCIS (Netherlands)

    Otten, Johannes D. M.; Broeders, Mireille J. M.; den Heeten, Gerard J.; Holland, Roland; Fracheboud, Jacques; de Koning, Harry J.; Verbeek, André L. M.

    2010-01-01

    BACKGROUND:: Screening can lead to earlier detection of breast cancer and thus to an improvement in survival. The authors studied the life expectancy of women with screen-detected invasive breast cancer (patients) compared with women invited to the breast cancer screening program in Nijmegen, the

  18. 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.

  19. Prognostic value of proliferation in invasive breast cancer: a review

    NARCIS (Netherlands)

    Diest, P.J. van; Wall, E. van der; Baak, J.P.A.

    2004-01-01

    Breast cancer is the leading cause of death among solid tumours in women, and its incidence is increasing in the West. Adjuvant chemotherapy and hormonal treatment improve survival but have potentially serious side effects, and are costly. Because adjuvant treatment should be given to high risk

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

    Science.gov (United States)

    2018-01-12

    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

  1. 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.

  2. The mammographic correlations of a new immunohistochemical classification of invasive breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Taneja, S. [Nottingham Breast Institute, City Hospital, Hucknall Road, Nottingham NG5 1PB (United Kingdom)], E-mail: sheeba_taneja@yahoo.co.uk; Evans, A.J. [Nottingham Breast Institute, City Hospital, Hucknall Road, Nottingham NG5 1PB (United Kingdom); Rakha, E.A.; Green, A.R. [Division of Pathology, School of Molecular Medical Sciences, Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham (United Kingdom); Ball, G. [Nottingham Trent University, School of Biomedical and Natural Sciences, Nottingham (United Kingdom); Ellis, I.O. [Division of Pathology, School of Molecular Medical Sciences, Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham (United Kingdom)

    2008-11-15

    Aim: Recent protein expression profiling of breast cancer has identified specific subtypes with clinical, biological, and therapeutic implications. The aim of this study was to identify the mammographic correlates of these novel molecular classes of invasive breast cancer. Materials and methods: The mammographic findings of 415 patients with operable breast cancer were correlated with the previously described protein expression classes identified by our group using immunohistochemical (IHC) assessment of a large series of breast cancer cases prepared as tissue microarrays (TMAs). Twenty-five proteins of known relevance in breast cancer were assessed, including hormone receptors, HER-2 status, basal and luminal markers, p53 expression, and E-cadherin. Results: The mammographic background pattern and proportion of lesions that were mammographically occult were similar in all groups. Groups characterized by luminal and hormone receptor positivity had significantly more spiculate lesions at mammography. Groups characterized by HER-2 overexpression, basal characteristics, and E-cadherin positivity had a significantly higher proportion of ill-defined masses. These findings were independent of histological grade. Conclusion: The mammographic features of breast cancer show significant correlation with molecular classes of invasive breast cancer identified by protein expression IHC analysis. The biological reasons for the findings and implications of these regarding imaging protocols require further study and may provide mechanisms for improvement of detection of these lesions.

  3. Inflammatory Breast Cancer

    Science.gov (United States)

    ... breast cancer correctly. Their recommendations are summarized below. Minimum criteria for a diagnosis of inflammatory breast cancer ... Initial biopsy samples from the affected breast show invasive carcinoma. Further examination of tissue from the affected ...

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

    Science.gov (United States)

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

    2017-04-01

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

  5. Predictors of competing mortality to invasive breast cancer incidence in the Canadian National Breast Screening study

    Directory of Open Access Journals (Sweden)

    Taghipour Sharareh

    2012-07-01

    Full Text Available Abstract Background Evaluating the cost-effectiveness of breast cancer screening requires estimates of the absolute risk of breast cancer, which is modified by various risk factors. Breast cancer incidence, and thus mortality, is altered by the occurrence of competing events. More accurate estimates of competing risks should improve the estimation of absolute risk of breast cancer and benefit from breast cancer screening, leading to more effective preventive, diagnostic, and treatment policies. We have previously described the effect of breast cancer risk factors on breast cancer incidence in the presence of competing risks. In this study, we investigate the association of the same risk factors with mortality as a competing event with breast cancer incidence. Methods We use data from the Canadian National Breast Screening Study, consisting of two randomized controlled trials, which included data on 39 risk factors for breast cancer. The participants were followed up for the incidence of breast cancer and mortality due to breast cancer and other causes. We stratified all-cause mortality into death from other types of cancer and death from non-cancer causes. We conducted separate analyses for cause-specific mortalities. Results We found that “age at entry” is a significant factor for all-cause mortality, and cancer-specific and non-cancer mortality. “Menstruation length” and “number of live births” are significant factors for all-cause mortality, and cancer-specific mortality. “Ever noted lumps in right/left breasts” is a factor associated with all-cause mortality, and non-cancer mortality. Conclusions For proper estimation of absolute risk of the main event of interest common risk factors associated with competing events should be identified and considered.

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

    NARCIS (Netherlands)

    Michaut, M; Chin, SF; Majewski, I; Severson, TM; Bismeijer, T; de Koning, L; Peeters, JK; Schouten, PC; Rueda, OM; Bosma, AJ; Wessels, L.F.A.; Authors, More

    2016-01-01

    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

  7. 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.

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

    NARCIS (Netherlands)

    van der Velden, Bas; Dmitriev, Ivan; Loo, C.E.; Pijnappel, Ruud; Gilhuijs, Kenneth

    2015-01-01

    Purpose To retrospectively investigate whether parenchymal enhancement in dynamic contrast material–enhanced magnetic resonance (MR) imaging of the contralateral breast in patients with unilateral invasive breast cancer is associated with therapy outcome. Materials and Methods After obtaining

  9. 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

  10. 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.

  11. 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

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

    Science.gov (United States)

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

    2010-07-01

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

  13. 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.

  14. 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

  15. 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

    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...... ovarian cancer. Eleven SNPs were initially genotyped in 2927 invasive ovarian cancer cases and 4143 controls from six ovarian cancer case-control studies. Genotype frequencies in cases and controls were compared using a likelihood ratio test in a logistic regression model stratified by study. Initially......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...

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Marta Hergueta-Redondo

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

  18. Breaking down barriers: the importance of the stromal microenvironment in acquiring invasiveness in young women's breast cancer

    OpenAIRE

    Schedin, Pepper; Borges, Virginia

    2009-01-01

    Gene expression profiling was performed on laser captured breast stroma and epithelium obtained from 14 breast cancer patients. As with breast epithelium, of the stromal gene expression changes observed between normal tissue and invasive ductal carcinoma, greater than 90% occurred early, at the normal to ductal carcinoma in situ transition. Only 10% of stromal and 0% of epithelial genes were differentially regulated between non-invasive ductal carcinoma in situ and invasive disease. These dat...

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

    Science.gov (United States)

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

    2011-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Mateusz Zajac

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

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

    OpenAIRE

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

    2015-01-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

  3. 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.

  4. 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

  5. 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.|info:eu-repo/dai/nl/338877169; van der Wall, Elsken; Mali, W.P.T.M.; Derksen, Patrick W B|info:eu-repo/dai/nl/256054797; van Diest, Paul J.|info:eu-repo/dai/nl/075281775; 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

  6. 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

  7. 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.

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

    Science.gov (United States)

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

    2014-07-09

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

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

    Science.gov (United States)

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

    2017-04-01

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

  10. Invasive Breast Cancer Incidence Trends by Detailed Race/Ethnicity and Age

    Science.gov (United States)

    Liu, Lihua; Zhang, Juanjuan; Wu, Anna H.; Pike, Malcolm C.; Deapen, Dennis

    2011-01-01

    Racial/ethnic disparities in breast cancer incidence may contain important evidence for understanding and control of the disease. Monitoring the incidence trends of breast cancer by race/ethnicity allows identification of high risk groups and development of targeted prevention programs. Using population-based cancer registry data from the Los Angeles Cancer Surveillance Program, we examined the invasive female breast cancer incidence trends among the diverse racial/ethnic populations in Los Angeles County, California, from 1972 to 2007. Age-adjusted incidence rates (AAIR) and age-specific incidence rates (ASIR) were calculated and examined respectively for non-Hispanic (NH) white, black, Hispanic, Chinese, Filipina, Japanese, and Korean women by calendar year and time period. Rising trends of AAIR were found in all racial/ethnic groups during the 1980s and 1990s. The breast cancer risk increased more substantially in Japanese and Filipinas than in Chinese and Koreans. During 2000–2007, the trends of AAIR declined significantly among NH white women and slightly in blacks, remained unchanged for Hispanics, and continued to rise significantly among all Asian subgroups. The patterns of ASIR by race/ethnicity changed dramatically over time. By 2000–2007, younger Hispanic women had the lowest breast cancer risk, replacing the Chinese and Koreans who formerly had the lowest risk. Rapidly increasing breast cancer incidence trends among Asian-Americans underline the importance of behavioral and lifestyle changes as a result of acculturation on the development of the disease. The unique trends of breast cancer incidence by race/ethnicity suggest the need for targeted breast cancer control programs for different racial/ethnic populations. PMID:21351091

  11. 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.

  12. Associations between gene expression profiles of invasive breast cancer and Breast Imaging Reporting and Data System MRI lexicon.

    Science.gov (United States)

    Kim, Ga Ram; Ku, You Jin; Cho, Soon Gu; Kim, Sei Joong; Min, Byung Soh

    2017-07-01

    To evaluate whether the Breast Imaging Reporting and Data System (BI-RADS) MRI lexicon could reflect the genomic information of breast cancers and to suggest intuitive imaging features as biomarkers. Matched breast MRI data from The Cancer Imaging Archive and gene expression profile from The Cancer Genome Atlas of 70 invasive breast cancers were analyzed. Magnetic resonance images were reviewed according to the BI-RADS MRI lexicon of mass morphology. The cancers were divided into 2 groups of gene clustering by gene set enrichment an alysis. Clinicopathologic and imaging characteristics were compared between the 2 groups. The luminal subtype was predominant in the group 1 gene set and the triple-negative subtype was predominant in the group 2 gene set (55 of 56, 98.2% vs. 9 of 14, 64.3%). Internal enhancement descriptors were different between the 2 groups; heterogeneity was most frequent in group 1 (27 of 56, 48.2%) and rim enhancement was dominant in group 2 (10 of 14, 71.4%). In group 1, the gene sets related to mammary gland development were overexpressed whereas the gene sets related to mitotic cell division were overexpressed in group 2. We identified intuitive imaging features of breast MRI associated with distinct gene expression profiles using the standard imaging variables of BI-RADS. The internal enhancement pattern on MRI might reflect specific gene expression profiles of breast cancers, which can be recognized by visual distinction.

  13. 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

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

    Directory of Open Access Journals (Sweden)

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

    Science.gov (United States)

    Valle Oseguera, Cendy A; Spencer, Juliet V

    2017-01-01

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

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

    Science.gov (United States)

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

    2017-10-01

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

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

    Directory of Open Access Journals (Sweden)

    Camila M. Lopes

    2015-12-01

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

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

    Science.gov (United States)

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

    2012-10-01

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

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

    Science.gov (United States)

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

    2017-07-18

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

  20. Risk factors for breast carcinoma in situ versus invasive breast cancer in a prospective study of pre- and post-menopausal women.

    Science.gov (United States)

    Reinier, Kyndaron S; Vacek, Pamela M; Geller, Berta M

    2007-07-01

    Risk factors for breast carcinoma in situ and invasive breast cancer were compared using data from 61,844 women (61% post-menopausal) with no prior breast cancer and at least one screening mammogram between April 1, 1996 and June 30, 2001. The women were followed until a subsequent mammogram before July 1, 2001, or a benign biopsy or breast cancer diagnosis before June 30, 2002. A total of 1,191 breast cancers (300 in situ and 891 invasive) were diagnosed during an average follow-up of 3.1 years. Multivariate Cox regression models were used to estimate the relative risks (RR) of in situ and invasive cancer associated with family history of breast cancer, age at first childbirth or nulliparity, post-menopausal hormone use, body mass index (BMI), and mammographic breast density. Separate analyses were done for pre- and post-menopausal women. BMI was unrelated to risk of in situ cancer regardless of menopausal status, but was associated with an increased risk of invasive cancer in post-menopausal women (RR = 1.9 for BMI > or = 30 vs. BMI < 22, 95% confidence interval 1.4-2.5). Later childbearing and nulliparity were more strongly associated with in situ than invasive cancer in pre-menopausal women. Post-menopausal hormone use was more strongly associated with invasive disease. RR associated with family history and breast density were similar for in situ cancer and invasive cancer. Results indicating that BMI is related to post-menopausal invasive cancers but unrelated to in situ cancers are consistent with the hypothesis that concomitants of obesity activate proliferation.

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

    Science.gov (United States)

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

    2014-12-30

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

  2. Acidosis promotes invasiveness of breast cancer cells through ROS-AKT-NF-κB pathway.

    Science.gov (United States)

    Gupta, Subash C; Singh, Ramesh; Pochampally, Radhika; Watabe, Kounosuke; Mo, Yin-Yuan

    2014-12-15

    It is well known that acidic microenvironment promotes tumorigenesis, however, the underlying mechanism remains largely unknown. In the present study, we show that acidosis promotes invasiveness of breast cancer cells through a series of signaling events. First, our study indicates that NF-κB is a key factor for acidosis-induced cell invasion. Acidosis activates NF-κB without affecting STAT3 activity; knockdown of NF-κB p65 abrogates the acidosis-induced invasion activity. Next, we show that the activation of NF-κB is mediated through phosphorylation and degradation of IκBα; and phosphorylation and nuclear translocation of p65. Upstream to NF-κB signaling, AKT is activated under acidic conditions. Moreover, acidosis induces generation of reactive oxygen species (ROS) which can be suppressed by ROS scavengers, reversing the acidosis-induced activation of AKT and NF-κB, and invasiveness. As a negative regulator of AKT, PTEN is oxidized and inactivated by the acidosis-induced ROS. Finally, inhibition of NADPH oxidase (NOX) suppresses acidosis-induced ROS production, suggesting involvement of NOX in acidosis-induced signaling cascade. Of considerable interest, acidosis-induced ROS production and activation of AKT and NF-κB can be only detected in cancer cells, but not in non-malignant cells. Together, these results demonstrate a cancer specific acidosis-induced signaling cascade in breast cancer cells, leading to cell invasion.

  3. 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.

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

    Directory of Open Access Journals (Sweden)

    Yan-gao Man

    2010-01-01

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

  5. 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

  6. Reduction in late-stage breast cancer incidence in the mammography era: Implications for overdiagnosis of invasive cancer.

    Science.gov (United States)

    Helvie, Mark A; Chang, Joanne T; Hendrick, R Edward; Banerjee, Mousumi

    2014-09-01

    Mammographic screening is expected to decrease the incidence of late-stage breast cancer. In the current study, the authors determined the decrease in late-stage cancer incidence and the changes in invasive cancer incidence that occurred in the mammographic era after adjusting for prescreening temporal trends. Breast cancer incidence and stage data were obtained from the Surveillance, Epidemiology, and End Results program. The premammography period (1977-1979) was compared with the mammographic screening period (2007-2009) for women aged ≥ 40 years. The authors estimated prescreening temporal trends using 5 measures of annual percentage change (APC). Stage-specific incidence values from 1977 through 1979 (baseline) were adjusted using APC values of 0.5%, 1.0%, 1.3%, and 2.0% and then compared with observed stage-specific incidence in 2007 through 2009. Prescreening APC temporal trend estimates ranged from 0.8% to 2.3%. The joinpoint estimate of 1.3% for women aged ≥ 40 years approximated the 4-decade long APC trend of 1.2% noted in the Connecticut Tumor Registry. At an APC of 1.3%, late-stage breast cancer incidence decreased by 37% (56 cases per 100,000 women) with a reciprocal increase in early-stage rates noted from 1977 through 1979 to 2007 through 2009. Resulting late-stage cancer incidence decreased from 21% at an APC of 0.5% to 48% at an APC of 2.0%. Total invasive breast cancer incidence decreased by 9% (27 cases per 100,000 women) at an APC of 1.3%. There is evidence that a substantial reduction in late-stage breast cancer has occurred in the mammography era when appropriate adjustments are made for prescreening temporal trends. At background APC estimates of ≥ 1%, the total invasive breast cancer incidence also decreased. © 2014 American Cancer Society.

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

    Science.gov (United States)

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

    2017-06-01

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

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

    Directory of Open Access Journals (Sweden)

    Cano Amparo

    2009-03-01

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

  9. 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

  10. 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...

  11. Baseline mammographic breast density and the risk of invasive breast cancer in postmenopausal women participating in the NSABP Study of Tamoxifen and Raloxifene (STAR)

    Science.gov (United States)

    Cecchini, Reena S.; Costantino, Joseph P.; Cauley, Jane A.; Cronin, Walter M.; Wickerham, D. Lawrence; Bandos, Hanna; Weissfeld, Joel L.; Wolmark, Norman

    2012-01-01

    Mammographic breast density is an established risk factor for breast cancer. However, results are inconclusive regarding its use in risk prediction models. The current study evaluated 13,409 postmenopausal participants in the NSABP Study of Tamoxifen and Raloxifene. A measure of breast density as reported on the entry mammogram report was extracted and categorized according to The American College of Radiology Breast Imaging Reporting and Data System (BI-RADS) classifications. An increased risk of invasive breast cancer was associated with higher mammographic breast density (Pbreast density and Gail score. Breast density was also significant when added to an abbreviated model tailored for estrogen receptor-positive breast cancers (P=0.02). In this study, high BI-RADS breast density was significantly associated with increased breast cancer risk when considered in conjunction with Gail score but provided only slight improvement to the Gail score for predicting the incidence of invasive breast cancer. The BI-RADS breast composition classification system is a quick and readily available method for assessing breast density for risk prediction evaluations; however, its addition to the Gail model does not appear to provide substantial predictability improvements in this population of postmenopausal healthy women at increased risk for breast cancer. PMID:23060039

  12. 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.

  13. VARIATION IN PRACTICE OF THE DIAGNOSTIC WORKUP OF ASYMPTOMATIC PATIENTS DIAGNOSED WITH INVASIVE BREAST CANCER

    Directory of Open Access Journals (Sweden)

    Anees eChagpar

    2016-03-01

    Full Text Available Introduction:Breast cancer is frequently diagnosed, yet variation remains in terms of practice patterns in presurgical workup. We sought to determine factors associated with this variation.Methods:An anonymous web-based survey was distributed to surgeons regarding their practices. Statistical analyses were conducted using SPSS.Results:253 surgeons responded to the survey. 17.0% were in academic practice, 37.5%% were hospital employed, and 41.5% were in private practice. 53.3% claimed that > 50% of their practice was breast-related. Surgeons were asked how often they would use various tests in the workup of an otherwise healthy asymptomatic patients, presenting with a non-palpable mammographic abnormality and a core needle biopsy showing invasive breast cancer. 23.5% stated they always would obtain a breast ultrasound, 17.2% stated they never would. 12.8% stated they never order a breast MRI; 4.1% always would. Workup of patients did not vary significantly based on number of years in practice nor practice setting. However, those whose practice was >50% breast were more likely to state that they would always order a breast ultrasound (32.5% vs. 12.9%, p<0.001, and less likely to state they would never order a breast MRI (3.4% vs. 25.8%, p<0.001. However, the proportions of surgeons who would always order a breast MRI was similar in the two groups (3.4% and 3.2%, respectively. Conclusions:These data highlight the lack of uniformity in the workup of asymptomatic patients presenting with non-palpable breast cancers, pointing to potential areas for improving value by minimizing variability.

  14. 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

  15. 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

  16. ABCB5-ZEB1 Axis Promotes Invasion and Metastasis in Breast Cancer Cells.

    Science.gov (United States)

    Yao, Juntao; Yao, Xuan; Tian, Tao; Fu, Xiao; Wang, Wenjuan; Li, Suoni; Shi, Tingting; Suo, Aili; Ruan, Zhiping; Guo, Hui; Nan, Kejun; Huo, Xiongwei

    2017-03-13

    ABCB5 belongs to the ATP-binding cassette (ABC) superfamily, which is recognized for playing a role in the failure of chemotherapy. ABCB5 has also been found to be overexpressed at the transcriptional level in a number of cancer subtypes, including breast cancer. However, the exact mechanism ABCB5 uses on cancer cell metastasis is still unclear. In the present study, we demonstrate that ABCB5 expression was increased in metastatic tissues when compared with nonmetastatic tissues. ABCB5 can significantly enhance metastasis and epithelial-mesenchymal transition (EMT), while knockdown of ABCB5 inhibited these processes. Microarray analysis indicated that ZEB1 may function as a downstream factor of ABCB5. Furthermore, the expression of ZEB1 in tissues is positively relevant to ABCB5 in breast cancer. Knocking down ZEB1 inhibits ABCB5 ectopic expression-induced migration and invasion, as well as EMT. Taken together, these results helped to realize the oncogene functions of ABCB5 in breast cancer cells and provided a new direction in treating breast cancer.

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

    Science.gov (United States)

    Li, Fanni; Li, Chenglin; Zhang, Haiwei; Lu, Zhijian; Li, Zhiyu; You, Qidong; Lu, Na; Guo, Qinglong

    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. Copyright © 2012 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    2006-09-01

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

  19. Hair keratin KRT81 is expressed in normal and breast cancer cells and contributes to their invasiveness.

    Science.gov (United States)

    Nanashima, Naoki; Horie, Kayo; Yamada, Toshiyuki; Shimizu, Takeshi; Tsuchida, Shigeki

    2017-05-01

    Keratins are fibrous proteins. Hair keratins constitute hard structures such as the hair and nails, and cytokeratins have been used as markers of breast carcinoma. However, the expression and function of full-size hair keratin genes have not been previously demonstrated in breast cancer. We investigated the expression of the hair keratin, KRT81, and its function in human breast cancer and normal mammary epithelial cells. Western blotting showed full size 55-kDa KRT81 expression in the human breast cancer cell lines, MCF7, SKBR3 and MDA-MB-231, normal human mammary epithelial cells (HMEC), and non-neoplastic cells (MCF10A). Reverse transcription-polymerase chain reaction revealed that the full size KRT81, including its 5' region is expressed in breast cells. Immunohistochemical and immunofluorescence analyses showed that KRT81 was located in the cytoplasm. To investigate the function of KRT81, we knocked down KRT81 by siRNA in MCF10A cells. Microarray analysis revealed that the expression of genes related to invasion such as matrix metallopeptidase (MMP)9 was decreased. In KRT81-knockdown MDA-MB231 cells, zymography revealed a decrease in MMP9 activity, while scratch and invasion assays revealed that KRT81-knockdown decreased cell migration and invasion abilities. This is the first study showing that full size KRT81 is expressed in normal breast epithelial cells and breast cancer cells. Moreover, our results indicate that KRT81 contributes to the migration and invasion of breast cancer cells.

  20. 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.

  1. Projecting Individualized Absolute Invasive Breast Cancer Risk in US Hispanic Women.

    Science.gov (United States)

    Banegas, Matthew P; John, Esther M; Slattery, Martha L; Gomez, Scarlett Lin; Yu, Mandi; LaCroix, Andrea Z; Pee, David; Chlebowski, Rowan T; Hines, Lisa M; Thompson, Cynthia A; Gail, Mitchell H

    2017-02-01

    There is no model to estimate absolute invasive breast cancer risk for Hispanic women. The San Francisco Bay Area Breast Cancer Study (SFBCS) provided data on Hispanic breast cancer case patients (533 US-born, 553 foreign-born) and control participants (464 US-born, 947 foreign-born). These data yielded estimates of relative risk (RR) and attributable risk (AR) separately for US-born and foreign-born women. Nativity-specific absolute risks were estimated by combining RR and AR information with nativity-specific invasive breast cancer incidence and competing mortality rates from the California Cancer Registry and Surveillance, Epidemiology, and End Results program to develop the Hispanic risk model (HRM). In independent data, we assessed model calibration through observed/expected (O/E) ratios, and we estimated discriminatory accuracy with the area under the receiver operating characteristic curve (AUC) statistic. The US-born HRM included age at first full-term pregnancy, biopsy for benign breast disease, and family history of breast cancer; the foreign-born HRM also included age at menarche. The HRM estimated lower risks than the National Cancer Institute's Breast Cancer Risk Assessment Tool (BCRAT) for US-born Hispanic women, but higher risks in foreign-born women. In independent data from the Women's Health Initiative, the HRM was well calibrated for US-born women (observed/expected [O/E] ratio = 1.07, 95% confidence interval [CI] = 0.81 to 1.40), but seemed to overestimate risk in foreign-born women (O/E ratio = 0.66, 95% CI = 0.41 to 1.07). The AUC was 0.564 (95% CI = 0.485 to 0.644) for US-born and 0.625 (95% CI = 0.487 to 0.764) for foreign-born women. The HRM is the first absolute risk model that is based entirely on data specific to Hispanic women by nativity. Further studies in Hispanic women are warranted to evaluate its validity. Published by Oxford University Press 2016. This work is written by US Government employees and is in the

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

    Science.gov (United States)

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

    2015-11-17

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-10-13

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

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

    Science.gov (United States)

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

    2015-08-18

    The o,p'-dichlorodiphenyltrichloroethane (DDT) with a chiral center possesses enantioselective estrogenic activity, in which R-(-)-o,p'-DDT exerts a more potent estrogenic effect than S-(+)-o,p'-DDT. Although concern regarding DDT exposure and breast cancer has increased in recent decades, the mode of enantioselective action of o,p'-DDT in breast cancer development is still unknown. Herein, we conducted a systematic study of the effect of o,p'-DDT on stereoselective breast tumor cell progression in a widely used in vitro breast tumor cell model, MCF-7 cells. We demonstrated that R-(-)-o,p'-DDT promoted more cancer cell invasion mediated by the human estrogen receptor (ER) by inducing invasion-promoted genes (matrix metalloproteinase-2 and -9 and human telomerase reverse transcriptase) and inhibiting invasion-inhibited genes (tissue inhibitor of metalloproteinase-1 and -4). Molecular docking verified that the binding affinity between R-(-)-o,p'-DDT and human ER was stronger than that of S-(+)-o,p'-DDT. The enantioselective-induced decrease in cell-to-cell adhesion may involve the downregulation of adhesion-promoted genes (E-cadherin and β-catenin). For the first time, these results reveal that estrogenic-like chiral compounds are of significant concern in the progression of human cancers and that human health risk assessment of chiral chemicals should consider enantioselectivity.

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

    Science.gov (United States)

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

    2014-07-01

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

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

    DEFF Research Database (Denmark)

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

    2015-01-01

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

  7. 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.

  8. 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

  9. Study of Estrogen Receptor and Progesterone Receptor Expression in Breast Ductal Carcinoma In Situ by Immunohistochemical Staining in ER/PgR-Negative Invasive Breast Cancer.

    Science.gov (United States)

    Dobrescu, Andrei; Chang, Monique; Kirtani, Vatsala; Turi, George K; Hennawy, Randa; Hindenburg, Alexander A

    2011-01-01

    Background. To our knowledge, the hormone receptor status of noncontiguous ductal carcinoma in situ (DCIS) occurring concurrently in ER/PgR-negative invasive cancer has not been studied. The current study was undertaken to investigate the ER/PgR receptor status of DCIS of the breast in patients with ER/PgR-negative invasive breast cancer. Methods. We reviewed the immunohistochemical (IHC) staining for ER and PgR of 187 consecutive cases of ER/PgR-negative invasive breast cancers, collected from 1995 to 2002. To meet the criteria for the study, we evaluated ER/PgR expression of DCIS cancer outside of the invasive breast cancer. Results. A total of 37 cases of DCIS meeting the above criteria were identified. Of these, 16 cases (43.2%) showed positive staining for ER, PgR, or both. Conclusions. In our study of ER/PgR-negative invasive breast cancer we found that in 8% of cases noncontiguous ER/PR-positive DCIS was present. In light of this finding, it may be important for pathologists to evaluate the ER/PgR status of DCIS occurring in the presence of ER/PgR-negative invasive cancer, as this subgroup could be considered for chemoprevention.

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

    Science.gov (United States)

    2017-06-07

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

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

    Science.gov (United States)

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

    2015-09-01

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

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

    DEFF Research Database (Denmark)

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

    2015-01-01

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

  13. The forkhead box transcription factor FOXC1 promotes breast cancer invasion by inducing matrix metalloprotease 7 (MMP7) expression.

    Science.gov (United States)

    Sizemore, Steven T; Keri, Ruth A

    2012-07-13

    Therapeutic options for treatment of basal-like breast cancers are limited and identification of molecular targets for novel therapies to treat this aggressive cancer is urgently needed. Recently, FOXC1, a forkhead box transcription factor, was identified as a functionally important biomarker of breast cancer aggressiveness and the basal-like breast cancer subtype. However, the mechanism through which FOXC1 controls aggressiveness of basal-like breast cancer remains to be elucidated. Here, we identify matrix metalloprotease 7 (MMP7) as a key downstream effector of FOXC1-mediated invasiveness. Expression of FOXC1 and MMP7 is significantly correlated in breast cancer samples and cell lines at both the mRNA and protein levels. Transient expression of FOXC1 in nontransformed mammary epithelial cell lines resulted in significantly increased expression of MMP7 and an MMP7-dependent increase in invasiveness. In reciprocal experiments, silencing endogenous FOXC1 in basal-like breast cancer cell lines resulted in decreased expression of MMP7 without decreased expression of other matrix metalloproteinases. We also demonstrate that elevated co-expression of FOXC1 and MMP7 is an independent predictor of patient outcome in multivariate analyses of two breast cancer patient cohorts. Together, our findings identify MMP7 as a novel mechanism through which FOXC1 may regulate the basal-like breast cancer invasive phenotype and the propensity of these cancers to metastasize. Furthermore, our findings demonstrate for the first time a correlation between MMP7 expression and basal-like breast cancers, suggesting that MMP7 may be a useful therapeutic target for treatment of this disease.

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

    Science.gov (United States)

    Şahin, Ertan; Elboğa, Umut

    2017-10-01

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

  15. Kindlin-2 could influence breast nodule elasticity and improve lymph node metastasis in invasive breast cancer.

    Science.gov (United States)

    Xue, Xiaowei; Li, Junlai; Wan, Wenbo; Shi, Xianquan; Zheng, Yiqiong

    2017-07-28

    This study investigated the relationship between quantitative parameters of shear wave elastography (SWE, maximum elasticity [Emax], minimum elasticity [Emin], mean elasticity [Emean]), collagen intensity and Kindlin-2 expression in benign and malignant breast nodules, and if Kindlin-2 expression is related with lymph node metastasis. A total of 102 breast nodules from 102 patients were included in our study who underwent ultrasound elastography before surgery or core needle biopsy. There was a significant difference between benign and malignant breast nodules in Emax, Emean, collagen intensity and Kindlin-2 expression, but it had no difference in Emin. Collagen intensity and Kindlin-2 expression both correlated positively with Emax, but not with Emean. Among 38 malignant breast nodules, the average Emax of the metastasis group was higher than that of the non-metastasis group, but it had no statistical significance. Compared with the non-metastasis group, Kindlin-2 expression was considerably higher in the metastasis group. However, there was no difference in collagen intensity between the metastasis group and the non-metastasis group. In conclusion, Kindlin-2 and collagen might contribute to breast nodule elasticity through molecular mechanisms. In breast cancer, overexpression of Kindlin-2 might be a risk factor for lymph node metastasis.

  16. Assessment of HER-2 status in invasive breast cancer in Brazil.

    Science.gov (United States)

    Arias, Victor Eduardo Arrua; Gobbi, Helenice; Ioshii, Sérgio Ossamu; Scapulatempo, Cristovam; Paz, Alexandre Rolim da; Silva, Vinicius Duval da; Uchôa, Diego; Zettler, Claudio; Soares, Fernando Augusto

    2017-07-01

    To characterize the frequency of HER-2-positive breast cancer in Brazil. In this prospective observational study, we first ascertained the HER-2 status of invasive breast cancer specimens by automated immunohistochemistry (IHC). For specimens classified as 2+ by IHC, we performed in situ hybridization (ISH). From February, 2011 to December, 2012, 1,495 breast specimens were registered, and 1,310 samples collected at 24 centers were analyzed. Median patient age was 54 years, and the majority of samples were obtained from segmental (46.9%) or radical mastectomy (34.4%). The predominant histological type was invasive breast carcinoma of no special type (85%), 64.3% had tubule formation (grade 3), and estrogen/progesterone receptors (ER/PR) were positive in 77.4/67.8% of the specimens analyzed, respectively. Using IHC, we found a negative HER-2 status (0 or 1+) in 72.2% of specimens, and 3+ in 18.5%; the 9.3% scored as 2+ were further analyzed by ISH, of which 15.7% were positive (thus, 20.0% of samples were HER-2- -positive by either method). We found no association between HER-2 scores and menopausal status or histological type. Tumors classified as 3+ came from younger patients, and had higher histological grade and less frequent expression of ER/PR. In the North region of Brazil, 34.7% of samples were 3+, with lower frequencies in the other four regions of the country. Our findings provide estimates for the frequency of HER-2 positivity in Brazil and raise the hypothesis that biological differences may underlie the different distribution of breast-cancer phenotypes among different Brazilian regions.

  17. Elemene inhibits the migration and invasion of 4T1 murine breast cancer cells via heparanase.

    Science.gov (United States)

    Zhang, Yi; Sun, Xu; Nan, Nan; Cao, Ke-Xin; Ma, Cong; Yang, Guo-Wang; Yu, Ming-Wei; Yang, Lin; Li, Jin-Ping; Wang, Xiao-Min; Zhang, Gan-Lin

    2017-07-01

    Elemene (ELE), a natural plant drug extracted from Curcumae Rhizoma, has been widely used for cancer treatment in China for more than 20 years. Although it is reported to be a broad‑spectrum anticancer drug, the mechanism underlying the action of ELE in the treatment of breast cancer remains to be fully elucidated. Heparanase, a mammalian endo‑D‑glucuronidase, is involved in degradation of the extracellular matrix (ECM), and thus promotes tumor progression and metastasis. The downregulation of heparanase can effectively reduce tumor malignant behaviors. In the present study, the inhibitory effects of ELE were evaluated in breast cancer cells using a Cell Counting kit 8 assay. The migratory and invasive capabilities of cancer cells were investigated using a wound healing assay, real‑time cell analysis and a Transwell assay. In addition, western blot analysis was used to assess alterations in the expression levels of key proteins. The present results confirmed the antiproliferative and antimetastatic effects of ELE, using low‑molecular weight heparin (LMWH) as a positive control. In addition, ELE was demonstrated to downregulate the expression of heparanase, and decrease the phosphorylation of extracellular signal‑regulated kinase and AKT. These findings suggested that ELE may be a promising agent targeting heparanase in the treatment of breast cancer.

  18. Radiation therapy and chemotherapy after breast conserving surgery for invasive breast cancer: an intermediate result

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Seok Ho; Lee, Kyu Chan; Choi, Jin Ho; Lee, Young Don; Park, Heoung Kyu; Kim, Hyun Young; Park, Se Hoon [Gachon Medical School, Incheon (Korea, Republic of)

    2007-03-15

    Breast conserving surgery (BCS) followed by chemotherapy (CT{sub x}.) and radiation therapy (RT) is widely performed for the treatment of early breast cancer. This retrospective study was undertaken to evaluate our interim results in terms of failure patterns, survival and relative risk factors. From January 1999 through December 2003, 129 patients diagnosed with invasive breast cancer and treated with BCS followed by RT were subject to retrospective review. The median age of the patients was 45 years (age distribution, 27 {approx} 76 years). The proportions of patients according to their tumor, nodes, and metastases (TNM) stage were 65 (50.4%) in stage I, 41 (31.7%) in stage IIa, 13 (10.1%) in stage IIb, 9 (7.0%) in stage III, and 1 patient (0.8%) in stage IIIc. For 32 patients (24.8%), axillary node metastasis was found after dissection, BCS consisted of quadrantectomy in 115 patients (89.1%) and lumpectomy in 14 patients (10.6%). Axillary node dissection at axillary level I and II was performed for 120 patients (93%). For 7 patients (5.4%), only sentinel node dissection was performed with BCS. For 2 patients (1.6%) axillary dissection of any type was not performed. Postoperative RT was given with 6 MV X-rays. A tumor dose of 50.4 Gy was delivered to the entire breast area using a tangential field with a wedge compensator. An additional dose of 9 {approx} 16 Gy was given to the primary tumor bed areas with electron beams. In 30 patients (23.3%), RT was delivered to the supraclavicular node. Most patients had adjuvant CT{sub x}. with 4 {approx} 6 cycles of CMF (cyclophosphamide, methotrexate, 5-fluorouracil) regimens. The median follow-up period was 50 months (range: 17 {approx} 93 months). The actuarial 5 year survival rate (5Y-OSR) was 96.9%, and the 5 year disease free survival rate (5Y-DFSR) was 93.7%. Local recurrences were noted in 2 patients (true: 2, regional node: 1) as the first sign of recurrence at a mean time of 29.3 months after surgery. Five

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

    Science.gov (United States)

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

    2013-05-01

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

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

    Science.gov (United States)

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

    2008-01-01

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

  1. P08.23MULTIPLE CALCIFIED BRAIN METASTASES IN A MALE PATIENT WITH INVASIVE DUCTAL BREAST CANCER

    OpenAIRE

    Ressl, N.; Haindl, M.; Schenk, T.; Ungersboeck, K.; Sedivy, R.; Oberndorfer, S.

    2014-01-01

    Breast cancer in men is a rare disease and accounts for 1.6% of all malignancies of the breast. We report a case of a 51-year-old man with invasive ductal carcinoma of the breast with multiple calcified brain metastases. After modified radical mastectomy he received adjuvant chemotherapy with cyclophosphamide and doxorubicin, hormonal therapy and trastuzumab. About one year after initial diagnosis he developed a generalized epileptic seizure. Neuroradiological imaging (MRI) revealed multiple ...

  2. 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

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

    Science.gov (United States)

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

    2017-10-01

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

  4. A failure analysis of invasive breast cancer: most deaths from disease occur in women not regularly screened.

    Science.gov (United States)

    Webb, Matthew L; Cady, Blake; Michaelson, James S; Bush, Devon M; Calvillo, Katherina Zabicki; Kopans, Daniel B; Smith, Barbara L

    2014-09-15

    Mortality reduction from mammographic screening is controversial. Individual randomized trials and meta-analyses demonstrate statistically significant mortality reductions in all age groups invited to screening. In women actually screened, mortality reductions are greater. Individual trials and meta-analyses show varying rates of mortality reduction, leading to questions about screening's value and whether treatment advances have diminished the importance of early detection. This study hypothesized that breast cancer deaths predominantly occurred in unscreened women. Invasive breast cancers diagnosed between 1990 and 1999 were followed through 2007. Data included demographics, mammography use, surgical and pathology reports, and recurrence and death dates. Mammograms were categorized as screening or diagnostic based on absence or presence of breast signs or symptoms, and were substantiated by medical records. Breast cancer deaths were defined after documentation of prior distant metastases. Absence of recurrent cancer and lethal other diseases defined death from other causes. Invasive breast cancer failure analysis defined 7301 patients between 1990 and 1999, with 1705 documented deaths from breast cancer (n = 609) or other causes (n = 905). Among 609 confirmed breast cancer deaths, 29% were among women who had been screened (19% screen-detected and 10% interval cancers), whereas 71% were among unscreened women, including > 2 years since last mammogram (6%), or never screened (65%). Overall, 29% of cancer deaths were screened, whereas 71% were unscreened. Median age at diagnosis of fatal cancers was 49 years; in deaths not from breast cancer, median age at diagnosis was 72 years. Most deaths from breast cancer occur in unscreened women. To maximize mortality reduction and life-years gained, initiation of regular screening before age 50 years should be encouraged. Copyright © 2013 American Cancer Society.

  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. 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

  7. Local recurrence after breast-conserving therapy for invasive breast cancer: high incidence in young patients and association with poor survival

    NARCIS (Netherlands)

    Elkhuizen, P. H.; van de Vijver, M. J.; Hermans, J.; Zonderland, H. M.; van de Velde, C. J.; Leer, J. W.

    1998-01-01

    PURPOSE: To study risk factors for local recurrence (LR) after breast-conserving therapy (BCT) for invasive breast cancer and, for patients with an LR, the mode of detection, location, treatment, influence of radiation therapy, and impact on survival. METHODS AND MATERIALS: 1360 patients (median age

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

    Science.gov (United States)

    Muscella, Antonella; Vetrugno, Carla; Marsigliante, Santo

    2017-11-01

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

  9. Multivitamin supplement use and risk of invasive breast cancer

    NARCIS (Netherlands)

    Meulepas, J.M.; Newcomb, P.A.; Burnett-Hartman, A.N.; Hampton, J.M.; Trentham-Dietz, A.

    2010-01-01

    Objective: Multivitamin supplements are used by nearly half of middle-aged women in the USA. Despite this high prevalence of multivitamin use, little is known about the effects of multivitamins on health outcomes, including cancer risk. Our main objective was to determine the association between

  10. A preclinical mouse model of invasive lobular breast cancer metastasis

    NARCIS (Netherlands)

    Doornebal, Chris W.; Klarenbeek, Sjoerd; Braumuller, Tanya M.; Klijn, Christiaan N.; Ciampricotti, Metamia; Hau, Cheei-Sing; Hollmann, Markus W.; Jonkers, Jos; de Visser, Karin E.

    2013-01-01

    Metastatic disease accounts for more than 90% of cancer-related deaths, but the development of effective antimetastatic agents has been hampered by the paucity of clinically relevant preclinical models of human metastatic disease. Here, we report the development of a mouse model of spontaneous

  11. Surgical options for Chinese patients with early invasive breast cancer: Data from the Hong Kong Breast Cancer Registry

    Directory of Open Access Journals (Sweden)

    Sharon W.W. Chan

    2017-11-01

    Conclusion: Chinese patients have lower BCS and breast reconstruction rate. Besides cultural difference, patient-related factors such as age, education, marital status, mammography screening, the use of private medical facilities, and clinical characteristics including smaller tumor size and peripherally located tumor were significant predictors for type of surgical treatments in Chinese women with early breast cancer.

  12. 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

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

    DEFF Research Database (Denmark)

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

    2013-01-01

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

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

    Science.gov (United States)

    2016-10-11

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

  15. Migration and invasion enhancer 1 (MIEN1) is overexpressed in breast cancer and is a potential new therapeutic molecular target.

    Science.gov (United States)

    Zhao, H-B; Zhang, X-F; Wang, H-B; Zhang, M-Z

    2017-02-08

    Migration and invasion enhancer 1 (MIEN1) is a membrane-anchored protein that is highly expressed in various types of cancer, and is correlated with the PI3K/AKT pathway. The aim of this study was to investigate the expression of MIEN1 and its clinical pathological significance in breast cancer. We used immunohistochemical staining to examine the expression of MIEN1 in 40 samples of human breast cancer tissue and 10 samples taken from regions adjacent to normal breast tissue. The rate of detection of MIEN1 protein was 67.5%, which was significantly higher than that in adjacent non-cancerous breast tissue (0%, P cancer. Kaplan-Meier survival analysis showed that patients with positive MIEN1 protein expression had a lower overall survival rate than patients who did not express MIEN1. Downregulation of MIEN1 suppressed the expression of matrix metallopeptidase 9 by downregulating the expression of protein kinase B (also known as AKT) in breast cancer cells. Our results indicate that MIEN1 overexpression may facilitate migration and invasion in breast cancer, and MIEN1 is a potential molecular target for cancer chemotherapy.

  16. 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.

  17. Pregnancy-associated breast cancer and pregnancy following treatment for breast cancer, in a cohort of women from Victoria, Australia, with a first diagnosis of invasive breast cancer.

    Science.gov (United States)

    Bell, Robin J; Fradkin, Pamela; Parathithasan, Nishanthinie; Robinson, Penelope J; Schwarz, Max; Davis, Susan R

    2013-10-01

    This study examined pregnancy-associated breast cancer (PABC) and pregnancy following treatment for breast cancer. We analysed data from a questionnaire-based, prospective study of women diagnosed with breast cancer. Timing of diagnosis in relation to pregnancy was self-reported in the enrolment questionnaire. Women reported subsequent pregnancies in annual follow-up questionnaires, up to at least 5 years from diagnosis. Women with PABC made up 3.3% of women pregnancies following treatment. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. MiR-132 prohibits proliferation, invasion, migration, and metastasis in breast cancer by targeting HN1

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Zhan-Guo, E-mail: zhang_zhanguo@hotmail.com; Chen, Wei-Xun, E-mail: chenweixunclark@163.com; Wu, Yan-Hui, E-mail: wuyanhui84@126.com; Liang, Hui-Fang, E-mail: lianghuifang1997@126.com; Zhang, Bi-Xiang, E-mail: bixiangzhang@163.com

    2014-11-07

    Highlights: • MiR-132 is down-regulated in breast cancer tissues and cell lines. • MiR-132 directly regulates HN1 by binding its 3′ UTR. • MiR-132 shows regulatory role in proliferation, invasion, migration and metastasis. • HN1 is involved in miR-132-mediated cell behavior. • Aberrant HN1 is associated with worse overall survival of breast cancer patients. - Abstract: Accumulating evidence indicates that miRNAs play critical roles in tumorigenesis and cancer progression. This study aims to investigate the role and the underlying mechanism of miR-132 in breast cancer. Here, we report that miR-132 is significantly down-regulated in breast cancer tissues and cancer cell lines. Additional study identifies HN1 as a novel direct target of miR-132. MiR-132 down-regulates HN1 expression by binding to the 3′ UTR of HN1 transcript, thereby, suppressing multiple oncogenic traits such as cancer cell proliferation, invasion, migration and metastasis in vivo and in vitro. Overexpression of HN1 restores miR-132-suppressed malignancy. Importantly, higher HN1 expression is significantly associated with worse overall survival of breast cancer patients. Taken together, our data demonstrate a critical role of miR-132 in prohibiting cell proliferation, invasion, migration and metastasis in breast cancer through direct suppression of HN1, supporting the potential utility of miR-132 as a novel therapeutic strategy against breast cancer.

  19. 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

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

    Science.gov (United States)

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

    2013-02-01

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

  1. 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.

  2. 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.

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

    Science.gov (United States)

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

    2009-01-01

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

  4. Glucocorticoids induce CCN5/WISP-2 expression and attenuate invasion in oestrogen receptor-negative human breast cancer cells.

    Science.gov (United States)

    Ferrand, Nathalie; Stragier, Emilien; Redeuilh, Gérard; Sabbah, Michèle

    2012-10-01

    CCN5 (cysteine-rich 61/connective tissue growth factor/nephroblastoma overexpressed 5)/WISP-2 [WNT1 (wingless-type MMTV integration site family, member 1)-inducible signalling pathway protein 2] is an oestrogen-regulated member of the CCN family. CCN5 is a transcriptional repressor of genes associated with the EMT (epithelial-mesenchymal transition) and plays an important role in maintenance of the differentiated phenotype in ER (oestrogen receptor)-positive breast cancer cells. In contrast, CCN5 is undetectable in more aggressive ER-negative breast cancer cells. We now report that CCN5 is induced in ER-negative breast cancer cells such as MDA-MB-231 following glucocorticoid exposure, due to interaction of the endogenous glucocorticoid receptor with a functional glucocorticoid-response element in the CCN5 gene promoter. Glucocorticoid treatment of MDA-MB-231 cells is accompanied by morphological alterations, decreased invasiveness and attenuated expression of mesenchymal markers, including vimentin, cadherin 11 and ZEB1 (zinc finger E-box binding homeobox 1). Interestingly, glucocorticoid exposure did not increase CCN5 expression in ER-positive breast cancer cells, but rather down-regulated ER expression, thereby attenuating oestrogen pathway signalling. Taken together, our results indicate that glucocorticoid treatment of ER-negative breast cancer cells induces high levels of CCN5 expression and is accompanied by the appearance of a more differentiated and less invasive epithelial phenotype. These findings propose a novel therapeutic strategy for high-risk breast cancer patients.

  5. 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

  6. The PDZ protein TIP-1 facilitates cell migration and pulmonary metastasis of human invasive breast cancer cells in athymic mice.

    Science.gov (United States)

    Han, Miaojun; Wang, Hailun; Zhang, Hua-Tang; Han, Zhaozhong

    2012-05-25

    Tax-interacting protein 1 (TIP-1, also known as Tax1bp3) inhibited proliferation of colon cancer cells through antagonizing the transcriptional activity of beta-catenin. However, in this study, elevated TIP-1 expression levels were detected in human invasive breast cancers. Studies with two human invasive breast cancer cell lines indicated that RNAi-mediated TIP-1 knockdown suppressed the cell adhesion, proliferation, migration and invasion in vitro, and inhibited tumor growth in mammary fat pads and pulmonary metastasis in athymic mice. Biochemical studies showed that TIP-1 knockdown had moderate and differential effects on the beta-catenin-regulated gene expression, but remarkably down regulated the genes for cell adhesion and motility in breast cancer cells. The decreased expression of integrins and paxillin was accompanied with reduced cell adhesion and focal adhesion formation on fibronectin-coated surface. In conclusion, this study revealed a novel oncogenic function of TIP-1 suggesting that TIP-1 holds potential as a prognostic biomarker and a therapeutic target in the treatment of human invasive breast cancers. Copyright © 2012 Elsevier Inc. All rights reserved.

  7. 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.

  8. Preventing Breast Cancer: Making Progress

    Science.gov (United States)

    ... Navigation Bar Home Current Issue Past Issues Preventing Breast Cancer: Making Progress Past Issues / Fall 2006 Table of ... 000 women will have been diagnosed with invasive breast cancer, and nearly 41,000 women will die from ...

  9. c-Myb Enhances Breast Cancer Invasion and Metastasis through the Wnt/β-Catenin/Axin2 Pathway.

    Science.gov (United States)

    Li, Yihao; Jin, Ke; van Pelt, Gabi W; van Dam, Hans; Yu, Xiao; Mesker, Wilma E; Ten Dijke, Peter; Zhou, Fangfang; Zhang, Long

    2016-06-01

    The molecular underpinnings of aggressive breast cancers remain mainly obscure. Here we demonstrate that activation of the transcription factor c-Myb is required for the prometastatic character of basal breast cancers. An analysis of breast cancer patients led us to identify c-Myb as an activator of Wnt/β-catenin signaling. c-Myb interacted with the intracellular Wnt effector β-catenin and coactivated the Wnt/β-catenin target genes Cyclin D1 and Axin2 Moreover, c-Myb controlled metastasis in an Axin2-dependent manner. Expression microarray analyses revealed a positive association between Axin2 and c-Myb, a target of the proinflammatory cytokine IL1β that was found to be required for IL1β-induced breast cancer cell invasion. Overall, our results identified c-Myb as a promoter of breast cancer invasion and metastasis through its ability to activate Wnt/β-catenin/Axin2 signaling. Cancer Res; 76(11); 3364-75. ©2016 AACR. ©2016 American Association for Cancer Research.

  10. [Breast cancer surgery].

    Science.gov (United States)

    Vlastos, Georges; Berclaz, Gilles; Langer, Igor; Pittet-Cuenod, Brigitte; Delaloye, Jean-François

    2007-10-24

    Breast conserving surgery followed by radiation therapy is the treatment of choice for early breast cancer. For patients who choice or need a mastectomy, breast reconstruction provides an acceptable alternative. Breast cancer surgery has been evolving through minimally invasive approaches. Sentinel node biopsy has already remplaced axillary lymph node dissection in the evaluation of the axilla. Local ablation of the tumor may be a valuable alternative to surgery in the future.

  11. Gamma-secretase/Notch Signalling Pathway Inhibitor RO4929097 in Treating Patients With Advanced, Metastatic, or Recurrent Triple Negative Invasive Breast Cancer

    Science.gov (United States)

    2017-02-28

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

  12. 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

    2015-01-01

    Aims 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. Methods and results 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. Conclusions 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. PMID:25283075

  13. 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.

  14. 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)

  15. Severe depression more common in patients with ductal carcinoma in situ than early-stage invasive breast cancer patients

    NARCIS (Netherlands)

    Gregorowitsch, M.L. (M. L.); D.J. van den Bongard (Desirée); Young-Afat, D.A. (D. A.); J.-P. Pignol (Jean-Philippe); C.H. van Gils (Carla); May, A.M. (A. M.); H.M. Verkooijen (Helena)

    2017-01-01

    textabstractPurpose: Ductal carcinoma in situ (DCIS) is associated with an excellent prognosis; historical studies have shown similar levels of psychological distress in patients with DCIS and with early-stage invasive breast cancer (early-IBC). It is suggested that these results might have led to

  16. Immunohistochemical Assessment of Expression of Centromere Protein—A (CENPA) in Human Invasive Breast Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Rajput, Ashish B. [Department of Pathology and Molecular Medicine, Queen' s University, Kingston, ON K7L 3N6 (Canada); Hu, Nianping [Cancer Research institute, Queen' s University, Kingston, ON K7L 3N6 (Canada); Varma, Sonal; Chen, Chien-Hung [Department of Pathology and Molecular Medicine, Queen' s University, Kingston, ON K7L 3N6 (Canada); Ding, Keyue [NCIC Clinical Trials Group, Queen' s University, Kingston, ON K7L 3N6 (Canada); Park, Paul C. [Department of Pathology and Molecular Medicine, Queen' s University, Kingston, ON K7L 3N6 (Canada); Chapman, Judy-Anne W. [NCIC Clinical Trials Group, Queen' s University, Kingston, ON K7L 3N6 (Canada); SenGupta, Sandip K. [Department of Pathology and Molecular Medicine, Queen' s University, Kingston, ON K7L 3N6 (Canada); Madarnas, Yolanda [Cancer Research institute, Queen' s University, Kingston, ON K7L 3N6 (Canada); Department of Oncology, Cancer Center of Southeastern Ontario, Kingston, ON K7L 2V7 (Canada); Elliott, Bruce E.; Feilotter, Harriet E., E-mail: feilotth@kgh.kari.net [Department of Pathology and Molecular Medicine, Queen' s University, Kingston, ON K7L 3N6 (Canada)

    2011-12-06

    Abnormal cell division leading to the gain or loss of entire chromosomes and consequent genetic instability is a hallmark of cancer. Centromere protein –A (CENPA) is a centromere-specific histone-H3-like variant gene involved in regulating chromosome segregation during cell division. CENPA is one of the genes included in some of the commercially available RNA based prognostic assays for breast cancer (BCa)—the 70 gene signature MammaPrint{sup ®} and the five gene Molecular Grade Index (MGI{sup SM}). Our aim was to assess the immunohistochemical (IHC) expression of CENPA in normal and malignant breast tissue. Clinically annotated triplicate core tissue microarrays of 63 invasive BCa and 20 normal breast samples were stained with a monoclonal antibody against CENPA and scored for percentage of visibly stained nuclei. Survival analyses with Kaplan–Meier (KM) estimate and Cox proportional hazards regression models were applied to assess the associations between CENPA expression and disease free survival (DFS). Average percentage of nuclei visibly stained with CENPA antibody was significantly higher (p = 0.02) in BCa than normal tissue. The 3-year DFS in tumors over-expressing CENPA (>50% stained nuclei) was 79% compared to 85% in low expression tumors (<50% stained nuclei). On multivariate analysis, IHC expression of CENPA showed weak association with DFS (HR > 60.07; p = 0.06) within our small cohort. To the best of our knowledge, this is the first published report evaluating the implications of increased IHC expression of CENPA in paraffin embedded breast tissue samples. Our finding that increased CENPA expression may be associated with shorter DFS in BCa supports its exploration as a potential prognostic biomarker.

  17. Meta-Analysis of Local Invasive Breast Cancer Recurrence After Electron Intraoperative Radiotherapy.

    Science.gov (United States)

    Harness, Jay K; Davies, Kalatu; Via, Christina; Brooks, Elizabeth; Zambelli-Weiner, April; Shah, Chirag; Vicini, Frank

    2017-11-06

    Electron intraoperative radiotherapy (IORT) can be used during breast conserving surgery to treat early-stage invasive breast cancer. Using data from current clinical and observational studies, this study aimed to assess the impact of single-fraction electron IORT on local recurrence rates. Studies on single-fraction electron IORT during breast conserving surgery were identified through a search of PubMed and Google Scholar, as well as through secondary referencing. Local recurrence rate was the main outcome of interest. A meta-analysis of proportions using a binomial distribution to model the within-study variability and a random effects model was conducted to estimate a pooled local recurrence rate. To estimate a 5-year recurrence rate, a single-sample Poisson-normal model was applied to model the probability of events occurring during a fixed period (60 months). The study identified 13 publications. The analysis demonstrated a pooled monthly local recurrence rate of 0.02% per person-month (95% confidence interval CI 0.00-0.06%) for the studies with a follow-up period shorter than 5 years, 0.03% per person-month (95% CI 0.02-0.06%) for studies with a follow-up period of 5 years or longer, and 0.02% per person-month (95% CI 0.01-0.04%) overall. Based on this model, the predicted 5-year local recurrence rate was 2.7% (range 1.9-3.7%). According to the published literature, the rate of breast cancer local recurrence after electron IORT was 0.02% per person-month, with an adjusted 5-year recurrence rate of 2.7%. These findings support the recent guidelines from the American Society for Radiation Oncology (ASTRO) supporting the use of electron IORT for low-risk patients.

  18. Immunohistochemical Assessment of Expression of Centromere Protein—A (CENPA in Human Invasive Breast Cancer

    Directory of Open Access Journals (Sweden)

    Bruce E. Elliott

    2011-12-01

    Full Text Available Abnormal cell division leading to the gain or loss of entire chromosomes and consequent genetic instability is a hallmark of cancer. Centromere protein –A (CENPA is a centromere-specific histone-H3-like variant gene involved in regulating chromosome segregation during cell division. CENPA is one of the genes included in some of the commercially available RNA based prognostic assays for breast cancer (BCa—the 70 gene signature MammaPrint® and the five gene Molecular Grade Index (MGISM. Our aim was to assess the immunohistochemical (IHC expression of CENPA in normal and malignant breast tissue. Clinically annotated triplicate core tissue microarrays of 63 invasive BCa and 20 normal breast samples were stained with a monoclonal antibody against CENPA and scored for percentage of visibly stained nuclei. Survival analyses with Kaplan–Meier (KM estimate and Cox proportional hazards regression models were applied to assess the associations between CENPA expression and disease free survival (DFS. Average percentage of nuclei visibly stained with CENPA antibody was significantly higher (p = 0.02 in BCa than normal tissue. The 3-year DFS in tumors over-expressing CENPA (>50% stained nuclei was 79% compared to 85% in low expression tumors ( 60.07; p = 0.06 within our small cohort. To the best of our knowledge, this is the first published report evaluating the implications of increased IHC expression of CENPA in paraffin embedded breast tissue samples. Our finding that increased CENPA expression may be associated with shorter DFS in BCa supports its exploration as a potential prognostic biomarker.

  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. 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, <50 and ≥50 years. One thousand one hundred and sixty-seven patients with IDC and ILC entered the study. A family history of malignancies was reported in 21.6 % of patients with IDC as opposed to 37.8 % of patients with ILC (P < 0.001). A history of gastric cancer was reported in 7.2 % in the ILC group as compared to 2.3 % in the IDC group, P < 0.008. A family history of breast 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.

  1. Mast cells in invasive ductal breast cancer: different behavior in high and minimum hormone-receptive cancers.

    Science.gov (United States)

    della Rovere, Filippo; Granata, Angelo; Familiari, Dario; D'Arrigo, Graziella; Mondello, Baldassare; Basile, Giacomo

    2007-01-01

    Studies on the role of mast cells (MC) in cancer have given contrasting results. In order to contribute to the clarification of their role, research on breast cancer was carried out, because some aspects of its carcinogenesis, such as the diversity of the hormonal component, differ greatly. This study included 50 cases of invasive ductal breast cancer not otherwise specified (NOS): 25 of them were high hormone-receptive (HHR) cancers with estrogen and progesterone receptor values not lower than 50%, 25 were minimum hormone-receptive (MHR) cancers (< 5%). In both groups, mast cells were quantified in the peritumoral area. Twenty cases of surgical interventions for non-neoplastic esthetic prosthesis in healthy women were examined as controls. The proliferation index Ki-67 (MIB1) and the c-erb B2 receptor protein were also considered in cancer patients. Mast cells were detected using Giemsa and Alcian blue stains. The results obtained showed that there was a highly significant increase in the number of mast cells mainly in the peritumoral area in HHR cancer cases (p < 0.0001) compared to MHR cancers and controls (p < 0.0001). Comparison between mast cells in MHR cancer and control cases was not significant (p = 0.114). Hormone-receptive cancers have a less severe prognosis for their higher responsiveness to therapy. This element may suggest that the higher mast cell number present in these types of cancer is a favorable prognostic factor. Moreover, mast cells tend to accumulate around the cancer area and this can be seen as an attempt to oppose the progression of the anomalous tissue. Mast cells were reported to exhibit cytolytic activity against tumor cells.

  2. PET/MR in invasive ductal breast cancer: correlation between imaging markers and histological phenotype.

    Science.gov (United States)

    Catalano, Onofrio Antonio; Horn, Gary Lloyd; Signore, Alberto; Iannace, Carlo; Lepore, Maria; Vangel, Mark; Luongo, Angelo; Catalano, Marco; Lehman, Constance; Salvatore, Marco; Soricelli, Andrea; Catana, Ciprian; Mahmood, Umar; Rosen, Bruce Robert

    2017-03-28

    Differences in genetics and receptor expression (phenotypes) of invasive ductal breast cancer (IDC) impact on prognosis and treatment response. Immunohistochemistry (IHC), the most used technique for IDC phenotyping, has some limitations including its invasiveness. We explored the possibility of contrast-enhanced positron emission tomography magnetic resonance (CE-FDG PET/MR) to discriminate IDC phenotypes. 21 IDC patients with IHC assessment of oestrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor-2 (HER2), and antigen Ki-67 (Ki67) underwent CE-FDG PET/MR. Magnetic resonance-perfusion biomarkers, apparent diffusion coefficient (ADC), and standard uptake value (SUV) were compared with IHC markers and phenotypes, using a Student's t-test and one-way ANOVA. ER/PR- tumours demonstrated higher Kepmean and SUVmax than ER or PR+ tumours. HER2- tumours displayed higher ADCmean, Kepmean, and SUVmax than HER2+tumours. Only ADCmean discriminated Ki67⩽14% tumours (lower ADCmean) from Ki67>14% tumours. PET/MR biomarkers correlated with IHC phenotype in 13 out of 21 patients (62%; P=0.001). Positron emission tomography magnetic resonance might non-invasively help discriminate IDC phenotypes, helping to optimise individual therapy options.

  3. Non-Invasive Breast Cancer Diagnosis through Electrochemical Biosensing at Different Molecular Levels

    Science.gov (United States)

    Campuzano, Susana

    2017-01-01

    The rapid and accurate determination of specific circulating biomarkers at different molecular levels with non- or minimally invasive methods constitutes a major challenge to improve the breast cancer outcomes and life quality of patients. In this field, electrochemical biosensors have demonstrated to be promising alternatives against more complex conventional strategies to perform fast, accurate and on-site determination of circulating biomarkers at low concentrations in minimally treated body fluids. In this article, after discussing briefly the relevance and current challenges associated with the determination of breast cancer circulating biomarkers, an updated overview of the electrochemical affinity biosensing strategies emerged in the last 5 years for this purpose is provided highlighting the great potentiality of these methodologies. After critically discussing the most interesting features of the electrochemical strategies reported so far for the single or multiplexed determination of such biomarkers with demonstrated applicability in liquid biopsy analysis, existing challenges still to be addressed and future directions in this field will be pointed out. PMID:28858236

  4. HER2/neu Immunostaining in Invasive Breast Cancer: Analysis of False Positive Factors

    Directory of Open Access Journals (Sweden)

    Maha Arafah

    2010-10-01

    Full Text Available Objectives: HER2/neu gene amplification by Fluorescent in situ hybridization and protein expression by immunohistochemistry have been used for prognosis and guidance for the treatment of invasive ductal carcinoma of the breast with Trastuzumab. False positive results are a significant problem where immunohistochemistry is exclusively used to test HER2/neu protein over expression. A minority of cases of breast cancer scoring HER2 (3+ by immunohistochemistry using Hercep test may not be associated with amplification of the HER2/neu gene by FISH, a test which is a more specific and sensitive than immunohistochemistry. This study aims to examine the factors contributing to false positive results by immunohistochemistry and subsequently not showing HER2/neu gene amplification by FISH analysis.Methods: A retrospective analysis of 18 cases (3+ by immunohistochemistry in the pathology laboratory not associated with HER2/neu gene amplification was performed. The histological review of these cases was done, the technical error (i.e staining of blood vessels or benign ducts and the interpretation errors were evaluated.Results: Polysomy 17 was absent in all the cases studied by FISH analysis. By immunohistochemistry, five of the 18 cases were purely interpretation errors and the remaining were a combination of technical and interpretational errors.Conclusion: False positive results related to technical and interpretational errors can be prevented by properly educating the technologist and pathologist to perform high quality immunostains and to render an accurate diagnosis respectively. This issue is of utmost importance as it may have deleterious effects on the selection of therapeutic arsenal in invasive ductal carcinoma of the breast.

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

    Science.gov (United States)

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

    2014-08-01

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

  6. Correlates of fear of cancer recurrence in women with ductal carcinoma in situ and early invasive breast cancer

    Science.gov (United States)

    Liu, Ying; Pérez, Maria; Schootman, Mario; Aft, Rebecca L.; Gillanders, William E.; Jeffe, Donna B.

    2011-01-01

    Fear of cancer recurrence (FCR) is a common and persistent concern among breast cancer survivors. Little is known about factors associated with FCR in women with ductal carcinoma in situ (DCIS) or early invasive breast cancer (EIBC). Women with first primary DCIS, or stages I–IIA breast cancer were prospectively enrolled in a quality-of-life study and completed interviews at 4–6 weeks, 6 months, and 2 years after definitive surgical treatment. In three stepwise multivariable linear regression models, including both time-independent and time-varying variables measured at each respective interview, we identified independent correlates of mean FCR scores (range 1–6) using four items from the Concern About Recurrence Scale (CARS) at 2-year follow-up. Of 506 disease-free patients at 2-year follow-up (mean [SD] age, 58 [10] years; 81% White; 34% DCIS), the average FCR score of 2.0 was low. However, 145 (29%) reported moderate-to-high levels of FCR (scores 3.0–6.0). All three models showed that younger age, stage IIA breast cancer (vs. DCIS), lower social support, and elevated anxiety were consistently associated with higher FCR at 2-year follow-up (each P < 0.05; final models R2 = 0.25–0.32). DCIS patients reported lower FCR than stage IIA patients (each P ≤ 0.01) but had similar FCR as stage I patients. Although mean FCR was low, 29% of DCIS and EIBC survivors reported moderate-to-high levels of FCR at 2-year follow-up. Management of anxiety, provision of social support, and patient education may help reduce FCR among DCIS and EIBC survivors, especially among younger survivors. PMID:21553295

  7. Breast Cancer

    Science.gov (United States)

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

  8. 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 cancer

  9. Phosphatidylinositol 4-phosphate in the Golgi apparatus regulates cell-cell adhesion and invasive cell migration in human breast cancer.

    Science.gov (United States)

    Tokuda, Emi; Itoh, Toshiki; Hasegawa, Junya; Ijuin, Takeshi; Takeuchi, Yukiko; Irino, Yasuhiro; Fukumoto, Miki; Takenawa, Tadaomi

    2014-06-01

    Downregulation of cell-cell adhesion and upregulation of cell migration play critical roles in the conversion of benign tumors to aggressive invasive cancers. In this study, we show that changes in cell-cell adhesion and cancer cell migration/invasion capacity depend on the level of phosphatidylinositol 4-phosphate [PI(4)P] in the Golgi apparatus in breast cancer cells. Attenuating SAC1, a PI(4)P phosphatase localized in the Golgi apparatus, resulted in decreased cell-cell adhesion and increased cell migration in weakly invasive cells. In contrast, silencing phosphatidylinositol 4-kinase IIIβ, which generates PI(4)P in the Golgi apparatus, increased cell-cell adhesion and decreased invasion in highly invasive cells. Furthermore, a PI(4)P effector, Golgi phosphoprotein 3, was found to be involved in the generation of these phenotypes in a manner that depends on its PI(4)P-binding ability. Our results provide a new model for breast cancer cell progression in which progression is controlled by PI(4)P levels in the Golgi apparatus. ©2014 American Association for Cancer Research.

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

    Science.gov (United States)

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

    2014-01-01

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

  11. 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.

  12. 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.

  13. 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.

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

    Science.gov (United States)

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

    2011-08-01

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

  15. 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

  16. 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...

  17. 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

  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; 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

  19. Predicting biopsy outcome after mammography: what is the likelihood the patient has invasive or in situ breast cancer?

    Science.gov (United States)

    Weaver, Donald L; Vacek, Pamela M; Skelly, Joan M; Geller, Berta M

    2005-08-01

    As many as 1,000,000 breast biopsies are performed annually in the United States. Although substantial effort has been devoted to estimating breast cancer risk, there have been no studies to predict outcome in women undergoing breast biopsy. A population-based study was undertaken to develop and test models for predicting the probability of invasive breast cancer and/or ductal carcinoma-in-situ in 7670 women undergoing breast biopsy after mammography. Logistical prediction models were developed by using data from 6129 randomly selected women and tested with data from the remaining women. The overall cancer prevalence among women undergoing biopsy was 22.4%. Prevalence in women with mammograms highly suggestive of malignancy (category 5) was 84.6%, with minimal variation in individual cancer probabilities due to age. A total of 24.6% of women with suspicious mammograms (category 4) had cancer, but individual probability estimates ranged from .01 to .86, depending on age, presence of a lump, previous biopsy, menopausal status, and use of postmenopausal hormone therapy. These variables also influenced biopsy outcome in women with other mammography assessments (categories 0-3), but the overall prevalence was lower (8.6%), and estimated probabilities ranged from .01 to .45. When cancer was present, the probability of invasive disease was influenced by mammogram assessment category, absence of mammogram calcifications, and presence of a lump. The probabilities of invasive cancer and ductal carcinoma-in-situ in women undergoing biopsy can be more accurately predicted by using clinical characteristics in addition to mammography findings. This information could potentially influence decisions regarding immediate biopsy or continued surveillance.

  20. FGF10: Type III Epithelial Mesenchymal Transition and Invasion in Breast Cancer Cell Lines

    Science.gov (United States)

    Abolhassani, Ali; Riazi, Gholam Hossein; Azizi, Ebrahim; Amanpour, Saeid; Muhammadnejad, Samad; Haddadi, Mahnaz; Zekri, Ali; Shirkoohi, Reza

    2014-01-01

    Purpose: Fibroblastic growth factor-10 (FGF-10) has an important role in type I epithelial mesenchymal transition (EMT) during the embryonic period of life (gastrulation). Since EMT has a critical role during cancer cells invasion and metastasis (type III) this study sought to investigate the possible role of FGF-10 in type III EMT by monitoring breast cancer cell lines' behavior by FGF-10 regulation. Methods: MCF-7 and MDA-MB-231 cell lines with different levels of FGF10 expression were treated with FGF-10 recombinant protein and FGF-10 siRNA, respectively. Results: The cell viability, migration, colony formation and wound healing have a direct relationship with FGF-10 expression, while FGF-10 expression decreased apoptosis. All mesenchymal factors (such as vimentin, N cadherin, snail, slug, TGF-β) increased due to FGF-10 expression with contrary expression of epithelial markers (such as E-cadherin). Moreover, GSK3β phosphorylation (inactivation) increased with FGF-10 expression. Conclusion: The important role of FGF-10 in type III EMT on cancer cells and initiation of metastasis via various kinds of signaling pathways has been suggested. PMID:25057305

  1. Computer-aided diagnosis of mammography using an artificial neural network: predicting the invasiveness of breast cancers from image features

    Science.gov (United States)

    Lo, Joseph Y.; Kim, Jeffrey; Baker, Jay A.; Floyd, Carey E., Jr.

    1996-04-01

    The study aim is to develop an artificial neural network (ANN) for computer-aided diagnosis of mammography. Using 9 mammographic image features and patient age, the ANN predicted whether breast lesions were benign, invasive malignant, or noninvasive malignant. Given only 97 malignant patients, the 3-layer backpropagation ANN successfully predicted the invasiveness of those breast cancers, performing with Az of 0.88 plus or minus 0.03. To determine more generalized clinical performance, a different ANN was developed using 266 consecutive patients (97 malignant, 169 benign). This ANN predicted whether those patients were benign or noninvasive malignant vs. invasive malignant with Az of 0.86 plus or minus 0.03. This study is unique because it is the first to predict the invasiveness of breast cancers using mammographic features and age. This knowledge, which was previously available only through surgical biopsy, may assist in the planning of surgical procedures for patients with breast lesions, and may help reduce the cost and morbidity associated with unnecessary surgical biopsies.

  2. 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

  3. β-elemene decreases cell invasion by upregulating E-cadherin expression in MCF-7 human breast cancer cells.

    Science.gov (United States)

    Zhang, Xian; Zhang, Yang; Li, Yinghua

    2013-08-01

    Inactivation of E-cadherin results in cell migration and invasion, hence leading to cancer aggressiveness and metastasis. Downregulation of E-cadherin is closely correlated with a poor prognosis in invasive breast cancer. Thus, re-introducing E-cadherin is a novel strategy for cancer therapy. The aim of the present study was to determine the effects of the traditional Chinese medicine, β-elemene (ELE), on E-cadherin expression, cell migration and invasion in the breast cancer cell line MCF-7. MCF-7 cells were treated with 50 and 100 µg/ml ELE. E-cadherin mRNA was analyzed by reverse transcription‑polymerase chain reaction. E-cadherin protein levels were determined by immunofluorescence and western blot assays. Cell motility was measured by a Transwell assay. ELE increased both the protein and mRNA levels of E-cadherin, accompanied by decreased cell migration and invasion. Further analysis demonstrated that ELE upregulated estrogen receptor‑α (ERα) and metastasis-associated protein 3 (MTA3), and decreased the nuclear transcription factor Snail. In conclusion, our results demonstrate that ELE decreases cell migration and invasion by upregulating E-cadherin expression via controlling the ERα/MTA3/Snail signaling pathway.

  4. 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.)

  5. 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.

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

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    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.

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

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    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.

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

    Science.gov (United States)

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

    2012-03-01

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

  9. Docosahexaenoic acid inhibits the invasion of MDA-MB-231 breast cancer cells through upregulation of cytokeratin-1.

    Science.gov (United States)

    Blanckaert, Vincent; Kerviel, Vincent; Lépinay, Alexandra; Joubert-Durigneux, Vanessa; Hondermarck, Hubert; Chénais, Benoît

    2015-01-01

    Docosahexaenoic acid (DHA), the main member of the omega-3 essential fatty acid family, has been shown to reduce the invasion of the triple-negative breast cancer cell line MDA-MB-231, but the mechanism involved remains unclear. In the present study, a proteomic approach was used to define changes in protein expression induced by DHA. Proteins from crude membrane preparations of MDA-MB-231 cells treated with 100 µM DHA were separated by two-dimensional electrophoresis (2-DE) and differentially expressed proteins were identified using MALDI-TOF mass spectrometry. The main changes observed were the upregulation of Keratin, type Ⅱ cytoskeletal 1 (KRT1), catalase and lamin-A/C. Immunocytochemistry analyses confirmed the increase in KRT1 induced by DHA. Furthermore, in vitro invasion assays showed that siRNA against KRT1 was able to reverse the DHA-induced inhibition of breast cancer cell invasion. In conclusion, KRT1 is involved in the anti-invasive activity of DHA in breast cancer cells.

  10. 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.

  11. 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.

  12. Surgical complications of skin sparing mastectomy and immediate prosthetic reconstruction after neoadjuvant chemotherapy for invasive breast cancer.

    Science.gov (United States)

    Donker, M; Hage, J J; Woerdeman, L A E; Rutgers, E J Th; Sonke, G S; Vrancken Peeters, M-J T F D

    2012-01-01

    Neoadjuvant chemotherapy is gaining acceptance as an option for breast cancer treatment, particularly in young women. These women may seek immediate breast reconstruction after mastectomy even though it is not known whether such preoperative chemotherapy may be detrimental to post-reconstruction wound healing. Therefore, we set out to assess the influence of neoadjuvant chemotherapy for invasive breast cancer on the short-term complications after skin sparing mastectomy and immediate prosthetic reconstruction. The short-term surgical outcome of 48 immediate breast reconstructions in 37 women treated with neoadjuvant chemotherapy from 2006 through 2009 was prospectively compared to that of 215 immediate reconstructions in 176 women who were operated in the same period without neoadjuvant chemotherapy. The overall rate of short-term postoperative complications was significantly less among neoadjuvantly treated women (15% vs. 29%; p = 0.042) but this did not result in a reduction of loss of prostheses (8% vs. 11%; p = 0.566). Because neoadjuvant chemotherapy is not associated with an increase in short-term complications after skin sparing mastectomy and immediate prosthetic reconstruction in patients with invasive breast cancer, such combined surgical therapy may be offered as treatment option for this particular group of patients also. Copyright © 2011 Elsevier Ltd. All rights reserved.

  13. Kindlin-2 could influence breast nodule elasticity and improve lymph node metastasis in invasive breast cancer

    National Research Council Canada - National Science Library

    Xiaowei Xue; Junlai Li; Wenbo Wan; Xianquan Shi; Yiqiong Zheng

    2017-01-01

    ... (SWE, maximum elasticity [Emax], minimum elasticity [Emin], mean elasticity [Emean]), collagen intensity and Kindlin-2 expression in benign and malignant breast nodules, and if Kindlin-2 expression is related with lymph node metastasis...

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

    Science.gov (United States)

    2017-06-07

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

  15. Kindlin-2 could influence breast nodule elasticity and improve lymph node metastasis in invasive breast cancer

    OpenAIRE

    Xue, Xiaowei; Li, Junlai; Wan, Wenbo; Shi, Xianquan; Zheng, Yiqiong

    2017-01-01

    This study investigated the relationship between quantitative parameters of shear wave elastography (SWE, maximum elasticity [Emax], minimum elasticity [Emin], mean elasticity [Emean]), collagen intensity and Kindlin-2 expression in benign and malignant breast nodules, and if Kindlin-2 expression is related with lymph node metastasis. A total of 102 breast nodules from 102 patients were included in our study who underwent ultrasound elastography before surgery or core needle biopsy. There was...

  16. 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.

  17. Evaluation of the potential for lymph node metastasis using CRP 1846C>T genetic polymorphism in invasive breast cancer.

    Science.gov (United States)

    Terata, Kaori; Motoyama, Satoru; Kamata, Shuichi; Hinai, Yudai; Miura, Masatomo; Sato, Yusuke; Yoshino, Kei; Ito, Aki; Imai, Kazuhiro; Saito, Hajime; Minamiya, Yoshihiro

    2014-06-01

    Lymph node status is a key indicator of the best approach to treatment of invasive breast cancer. However, the accuracy with which lymph node metastasis is diagnosed is not currently satisfactory. New and more reliable methods that enable one to know who has a greater potential for lymph node metastasis would be highly desirable. We previously reported that lymph node involvement in esophageal and lung cancer may have a genetic component: C-reactive protein (CRP) 1846C>T genetic polymorphism. Here we examined the diagnostic value of CRP 1846C>T polymorphism for assessing the risk of lymph node metastasis in cases of invasive breast cancer. The study participants were 185 women with invasive breast cancer who underwent curative surgery with lymph node dissection. Using DNA from blood samples and polymerase chain reaction-restriction fragment length polymorphism, the utility of CRP genetic 1846C>T polymorphism (rs1205) for assessing the risk of lymph node metastasis was evaluated. Fifty-two (28 %) patients had lymph node metastasis. After the patients were divided into two groups based on their CRP 1846 genotypes (C/C+C/T and T/T), the clinical characteristics did not differ between the groups, but there was a significantly greater incidence of lymph node metastasis among patients in the T/T group. Moreover, the odds ratio for lymph node involvement in patients carrying the 1846 T/T genotype was more than 2.2 in multivariate logistic regression models. CRP genetic polymorphism may be a novel predictor of the risk of lymph node metastasis in invasive breast cancer.

  18. Breast cancer

    Science.gov (United States)

    ... help you not feel alone. Outlook (Prognosis) New, improved treatments are helping people with breast cancer live ... carcinoma in situ Patient Instructions Breast radiation - discharge Chemotherapy - what to ask your doctor Lymphedema - self-care ...

  19. Compromised margins following mastectomy for stage I-III invasive breast cancer.

    Science.gov (United States)

    Yu, Jennifer; Al Mushawah, Fatema; Taylor, Marie E; Cyr, Amy E; Gillanders, William E; Aft, Rebecca L; Eberlein, Timothy J; Gao, Feng; Margenthaler, Julie A

    2012-09-01

    We investigated factors associated with positive margins following mastectomy and the impact on outcomes. We identified 240 patients with stage I-III invasive breast cancer who underwent mastectomy from 1999 to 2009. Data included patient and tumor characteristics, pathologic margin assessment, and outcomes. Margin positivity was defined as the presence of in situ or invasive malignancy at any margin. Descriptive statistics were used for data summary and were compared using χ(2). Of the 240 patients, 132 (55%) had a simple mastectomy with sentinel lymph node biopsy and 108 (45%) had a modified radical mastectomy. Overall, 21 patients (9%) had positive margins, including 12 (57%) with one positive margin, 3 (14%) with two positive margins, and 6 (29%) with three or more positive margins. The most commonly affected margin was the deep margin (48% of patients). Eight of the 21 patients (38%) received adjuvant chest wall irradiation. There were no differences between patients who had a positive margin and those who did not with respect to patient age, race, percentage of in situ component, tumor size, tumor grade, lymphovascular invasion, or immunostain profile (P > 0.05 for all). None of the patients with positive margins experienced a local recurrence. Positive margins following mastectomy occurred in nearly 10% of our patients. No specific patient or tumor characteristics predicted a risk for having a positive margin. Despite the finding that only approximately 40% of patients received adjuvant radiation in the setting of a positive margin, no local recurrences have been observed. Copyright © 2012 Elsevier Inc. All rights reserved.

  20. 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.

  1. 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.

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

    Science.gov (United States)

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

    2016-07-08

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

  3. Kempopeptin C, a Novel Marine-Derived Serine Protease Inhibitor Targeting Invasive Breast Cancer

    Directory of Open Access Journals (Sweden)

    Fatma H. Al-Awadhi

    2017-09-01

    Full Text Available Kempopeptin C, a novel chlorinated analogue of kempopeptin B, was discovered from a marine cyanobacterium collected from Kemp Channel in Florida. The structure was elucidated using NMR spectroscopy and mass spectrometry (MS. The presence of the basic Lys residue adjacent to the N-terminus of the 3-amino-6-hydroxy-2-piperidone (Ahp moiety contributed to its selectivity towards trypsin and related proteases. The antiproteolytic activity of kempopeptin C was evaluated against trypsin, plasmin and matriptase and found to inhibit these enzymes with IC50 values of 0.19, 0.36 and 0.28 μM, respectively. Due to the significance of these proteases in cancer progression and metastasis, as well as their functional redundancy with respect to targeting overlapping substrates, we examined the effect of kempopeptin C on the downstream cellular substrates of matriptase: CDCP1 and desmoglein-2 (Dsg-2. Kempopeptin C was shown to inhibit the cleavage of both substrates in vitro. Additionally, kempopeptin C reduced the cleavage of CDCP1 in MDA-MB-231 cells up to 10 µM. The functional relevance of targeting matriptase and related proteases was investigated by assessing the effect of kempopeptin C on the migration of breast cancer cells. Kempopeptin C inhibited the migration of the invasive MDA-MB-231 cells by 37 and 60% at 10 and 20 µM, respectively.

  4. Breast Cancer Prevention

    Science.gov (United States)

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

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

    Science.gov (United States)

    2011-10-01

    Rosenberg LU, Magnusson C, Lindstrom E, Wedren S, Hall P, Dickman PW. Menopausal hormone therapy and other breast cancer risk factors in relation...2876-2880. 39. Desruisseau S, Palmari J, Giusti C, Romain S, Martin PM, Berthois Y. Clinical relevance of amphiregulin and VEGF in primary breast

  6. Crosstalk between chemokine receptor CXCR4 and cannabinoid receptor CB2 in modulating breast cancer growth and invasion.

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    Mohd W Nasser

    Full Text Available BACKGROUND: Cannabinoids bind to cannabinoid receptors CB(1 and CB(2 and have been reported to possess anti-tumorigenic activity in various cancers. However, the mechanisms through which cannabinoids modulate tumor growth are not well known. In this study, we report that a synthetic non-psychoactive cannabinoid that specifically binds to cannabinoid receptor CB(2 may modulate breast tumor growth and metastasis by inhibiting signaling of the chemokine receptor CXCR4 and its ligand CXCL12. This signaling pathway has been shown to play an important role in regulating breast cancer progression and metastasis. METHODOLOGY/PRINCIPAL FINDINGS: We observed high expression of both CB(2 and CXCR4 receptors in breast cancer patient tissues by immunohistochemical analysis. We further found that CB(2-specific agonist JWH-015 inhibits the CXCL12-induced chemotaxis and wound healing of MCF7 overexpressing CXCR4 (MCF7/CXCR4, highly metastatic clone of MDA-MB-231 (SCP2 and NT 2.5 cells (derived from MMTV-neu by using chemotactic and wound healing assays. Elucidation of the molecular mechanisms using various biochemical techniques and confocal microscopy revealed that JWH-015 treatment inhibited CXCL12-induced P44/P42 ERK activation, cytoskeletal focal adhesion and stress fiber formation, which play a critical role in breast cancer invasion and metastasis. In addition, we have shown that JWH-015 significantly inhibits orthotopic tumor growth in syngenic mice in vivo using NT 2.5 cells. Furthermore, our studies have revealed that JWH-015 significantly inhibits phosphorylation of CXCR4 and its downstream signaling in vivo in orthotopic and spontaneous breast cancer MMTV-PyMT mouse model systems. CONCLUSIONS/SIGNIFICANCE: This study provides novel insights into the crosstalk between CB(2 and CXCR4/CXCL12-signaling pathways in the modulation of breast tumor growth and metastasis. Furthermore, these studies indicate that CB(2 receptors could be used for developing

  7. 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 note, the prognosis after the diagnosis of peritoneal metastases was poor, with a median survival time of 19 ± 9 months and resistance to hormone therapy. The extremely high rate (68.8%) of peritoneal metastases was observed in long-term follow-up for the metastatic breast cancer patients with ILC. We need to reveal the definitive feature of ILC and develop new therapeutic strategies to prevent the dissemination of ILCs.

  8. Invasive Breast Cancer Incidence in 2,305,427 Screened Asymptomatic Women: Estimated Long Term Outcomes during Menopause Using a Systematic Review.

    Directory of Open Access Journals (Sweden)

    Winnifred Cutler

    Full Text Available Earlier studies of breast cancer, screening mammography, and mortality reduction may have inflated lifetime and long-term risk estimates for invasive breast cancer due to limitations in their data collection methods and interpretation.To estimate the percentage of asymptomatic peri/postmenopausal women who will be diagnosed with a first invasive breast cancer over their next 25 years of life.A systematic review identified peer-reviewed published studies that: 1 enrolled no study participants with a history of invasive breast cancer; 2 specified the number of women enrolled; 3 reported the number of women diagnosed with a first invasive breast cancer; 4 did not overcount [count a woman multiple times]; and, 5 defined the length of follow-up. Data sources included PubMed, Cochrane Library, and an annotated library of 4,409 full-text menopause-related papers collected and reviewed by the first author from 1974 through 2008. Linear regression predicted incidence of first invasive breast cancer, based on follow-up duration in all studies that met the our inclusion criteria, and in a subset of these studies that included only women who were 1 at least 50 years old and 2 either at least 50 or less than 50 but surgically menopausal at enrollment.Nineteen studies met the inclusion criteria. They included a total of 2,305,427 peri/postmenopasual women. The mean cumulative incidence rate of first invasive breast cancer increased by 0.20% for each year of age (95% CI: 0.17, 0.23; p < 0.01; R2 = 0.90. Over 25 years of follow-up, an estimated 94.55% of women will remain breast cancer-free (95% CI: 93.97, 95.13. In the 12 studies (n = 1,711,178 that enrolled only postmenopausal women, an estimated 0.23% of women will be diagnosed with a first invasive breast cancer each year (95% CI: 0.18, 0.28; p < 0.01, R2 = 0.88.The vast majority (99.75% of screened asymptomatic peri/postmenopasual women will not be diagnosed with invasive breast cancer each year

  9. Invasive Breast Cancer Incidence in 2,305,427 Screened Asymptomatic Women: Estimated Long Term Outcomes during Menopause Using a Systematic Review.

    Science.gov (United States)

    Cutler, Winnifred; Bürki, Regula; Kolter, James; Chambliss, Catherine; Friedmann, Erika; Hart, Kari

    2015-01-01

    Earlier studies of breast cancer, screening mammography, and mortality reduction may have inflated lifetime and long-term risk estimates for invasive breast cancer due to limitations in their data collection methods and interpretation. To estimate the percentage of asymptomatic peri/postmenopausal women who will be diagnosed with a first invasive breast cancer over their next 25 years of life. A systematic review identified peer-reviewed published studies that: 1) enrolled no study participants with a history of invasive breast cancer; 2) specified the number of women enrolled; 3) reported the number of women diagnosed with a first invasive breast cancer; 4) did not overcount [count a woman multiple times]; and, 5) defined the length of follow-up. Data sources included PubMed, Cochrane Library, and an annotated library of 4,409 full-text menopause-related papers collected and reviewed by the first author from 1974 through 2008. Linear regression predicted incidence of first invasive breast cancer, based on follow-up duration in all studies that met the our inclusion criteria, and in a subset of these studies that included only women who were 1) at least 50 years old and 2) either at least 50 or less than 50 but surgically menopausal at enrollment. Nineteen studies met the inclusion criteria. They included a total of 2,305,427 peri/postmenopasual women. The mean cumulative incidence rate of first invasive breast cancer increased by 0.20% for each year of age (95% CI: 0.17, 0.23; p < 0.01; R2 = 0.90). Over 25 years of follow-up, an estimated 94.55% of women will remain breast cancer-free (95% CI: 93.97, 95.13). In the 12 studies (n = 1,711,178) that enrolled only postmenopausal women, an estimated 0.23% of women will be diagnosed with a first invasive breast cancer each year (95% CI: 0.18, 0.28; p < 0.01, R2 = 0.88). The vast majority (99.75%) of screened asymptomatic peri/postmenopasual women will not be diagnosed with invasive breast cancer each year. Approximately

  10. Breast cancer in situ. From pre-malignant lesion of uncertain significance to well-defined non-invasive malignant lesion. The Danish Breast Cancer Cooperative Group Register 1977-2007 revisited

    DEFF Research Database (Denmark)

    Laenkholm, A.V.; Jensen, Maiken Brit; Kroman, N.

    2008-01-01

    In addition to nationwide standardized pathology forms for operable primary invasive breast cancer, the Danish Breast Cancer cooperative Group (DBCG) in 1982 introduced pathology forms for breast cancer in situ (CIS). The histological reporting form was used primarily for ductal cancer in situ...... receptor (ER) and Progesteron receptor (PR) status. Also mastectomy specimens were included. In 2004 the previous malignancy grading was replaced by the Van Nuys classification, and information on microcalcifications was introduced. The axillary status now included the sentinel node technique only. In 2006...

  11. 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.

  12. Expression of ghrelin is correlated to a favorable outcome in invasive breast cancer.

    Science.gov (United States)

    Grönberg, Malin; Fjällskog, Marie-Louise; Jirström, Karin; Janson, Eva T

    2012-03-01

    Expression of the peptide hormones ghrelin and obestatin has previously been demonstrated in human mammary glands. However, the clinical implications of the expression of these peptides in breast cancer are unclear. The aim of this study was to investigate the potential clinical value of ghrelin and obestatin as breast cancer biomarkers. A tissue microarray containing breast cancer specimens from 144 patients was immunostained with antibodies directed towards ghrelin and obestatin. Using varying cut-offs, the expression of the two peptides was evaluated and correlated to previously known prognostic factors in breast cancer and to the outcome. Cox regression analysis was used to assess whether these markers may predict survival of breast cancer patients. Moderate to strong immunoreactivity for ghrelin and obestatin was observed in 71.5% and 77.1% of the cases, respectively. Ghrelin and obestatin expression was significantly but weakly correlated to low histological grade, estrogen receptor positivity, small tumor size and low proliferation. Only ghrelin expression was significantly correlated to better recurrence-free and breast cancer-specific survival (HR = 0.3-0.4, p = 0.02-0.05) in both uni- and multivariate analyses. The optimal cut-off was any ghrelin expression versus none. Reproducibility between the two readers was very good for both stainings with kappa values of 0.94-1.00. Patients with tumors expressing ghrelin had 2.5-3 times lower risk for recurrence or breast cancer death than those lacking ghrelin expression. Ghrelin expression is easily assessable with high reproducibility using immunohistochemistry. Further investigations are needed to establish the clinical significance of ghrelin as a biomarker in breast cancer.

  13. A Unique Case of Muscle-Invasive Metastatic Breast Cancer Mimicking Myositis

    Directory of Open Access Journals (Sweden)

    Janelle Gyorffy

    2017-01-01

    Full Text Available Breast cancer rarely metastasizes to the muscles, and it is even more unusual for this phenomenon to result in airway compromise. We present a unique case of an 84-year-old female who presented with neck swelling and upper airway obstruction due to metastatic breast cancer invading the sternocleidomastoid muscles. After establishing the diagnosis and discussing possible treatment options, the patient elected for antiestrogen therapy, palliative tracheostomy, radiation therapy, and hospice services.

  14. 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.

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

    Science.gov (United States)

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

    2010-07-01

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

  16. 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.

  17. 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

  18. Breast Cancer: Treatment Options

    Science.gov (United States)

    ... Breast Cancer > Breast Cancer: Treatment Options Request Permissions Breast Cancer: Treatment Options Approved by the Cancer.Net Editorial ... as possible. Learn more about palliative care . Recurrent breast cancer If the cancer does return after treatment for ...

  19. [Specific features of neovascularization of dysplastic invasiveness and cancer of the breast].

    Science.gov (United States)

    Khadyrov, E A; Mchedlishvili, M Iu

    2007-01-01

    There are shown the results of study related to angioarchitechtonices of displastic pre-cancer outgrows, fibroadenoma and carcinoma of the breast (non-proliferative and proliferative forms of fibro-cystic disease - 35 cases, fibroadenoma - 32 cases, cancer - 55 cases) using histological (hematoxylin and eosin and picrofuxin staining) and immunohistochemical (angiogenesis marker - CD31 and marker of proliferation - Ki67) methods. It was estimated that the character and intensity of vascularization as well as neoangiogenesis of above-named pathologic conditions and breast cancer could be determined by the differentiation of tissue structures and neoplastic cells. The microangioarxitectonics pre-cancer outgrowths and cancer of the breast is so peculiar and characteristic for each concrete case that it should be considered for morphological diagnosing and determining the tactic of treatment.

  20. 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.

  1. 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.

  2. Breast Cancer Treatment

    Science.gov (United States)

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

  3. Stages of Breast Cancer

    Science.gov (United States)

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

  4. Breast cancer screening

    Science.gov (United States)

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

  5. Immunohistochemical analysis of phosphorylated mammalian target of rapamycin and its downstream signaling components in invasive breast cancer.

    Science.gov (United States)

    Ma, Bin-Lin; Shan, Mei-Hui; Sun, Gang; Ren, Guang-Hui; Dong, Chao; Yao, Xuemei; Zhou, Mei

    2015-10-01

    The present study aimed to investigate whether the mammalian target of rapamycin (mTOR) signaling pathway is activated in invasive breast cancer. The expression levels of phosphorylated (p)‑mTOR at ser2448 were detected, as well as the expression levels of its downstream signaling molecules: Eukaryotic translation initiation factor 4E‑binding protein 1 (4E‑BP1), and p70 ribosomal protein S6 kinase 1 (S6K1). The correlation between p‑mTOR, p‑4E‑BP1, p‑S6K1, and the clinicopathological parameters of breast cancer were also determined. p‑mTOR, p‑4E‑BP1 and p‑S6K1 expression was detected in 285 breast cancer tumor samples and adjacent normal tissue samples using immunohistochemistry. The expression levels and the location of the proteins were analyzed and compared in the various tissue samples. Multivariate Cox regression was used to analyze the clinicopathological factors and prognosis associated with the tissue samples. The disease‑free survival rate was examined using survival analyses and Log‑rank tests. The results of the present study indicated that the expression levels of p‑mTOR, p‑4E‑BP1, and p‑S6K1 were significantly higher in breast cancer tissue, as compared with normal tissue (Pbreast cancer tissue samples, as compared with normal tissue samples (P0.05). Thus suggesting that these markers are not adequate risk factors for disease free survival (P>0.05). In conclusion, the results of the present study suggested that p‑mTOR, p‑4E‑BP1, and p‑S6K1 are activated in invasive breast cancer. In addition, the exclusive expression of p‑4E‑BP1 and p‑S6K1 in the cytoplasm may be characteristic of progressive breast cancer. However, p‑mTOR, p‑4E‑BP1, and p‑S6K1 are not prognostic factors for breast cancer.

  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. Paired ductal carcinoma in situ and invasive breast cancer lesions in the D-loop of the mitochondrial genome indicate a cancerization field effect.

    Science.gov (United States)

    Maggrah, Andrea; Robinson, Kerry; Creed, Jennifer; Wittock, Roy; Gehman, Ken; Gehman, Teresa; Brown, Helen; Harbottle, Andrew; Froberg, M Kent; Klein, Daniel; Reguly, Brian; Parr, Ryan

    2013-01-01

    Alterations in the mitochondrial genome have been chronicled in most solid tumors, including breast cancer. The intent of this paper is to compare and document somatic mitochondrial D-loop mutations in paired samples of ductal carcinoma in situ (DCIS) and invasive breast cancer (IBC) indicating a potential breast ductal epithelial cancerization field effect. Paired samples of these histopathologies were laser-captured microdissected (LCM) from biopsy, lumpectomy, and mastectomy tissues. Blood samples were collected as germplasm control references. For each patient, hypervariable region 1 (HV1) in the D-loop portion of the mitochondrial genome (mtGenome) was sequenced for all 3 clinical samples. Specific parallel somatic heteroplasmic alterations between these histopathologies, particularly at sites 16189, 16223, 16224, 16270, and 16291, suggest the presence of an epithelial, mitochondrial cancerization field effect. These results indicate that further characterization of the mutational pathway of DCIS and IBC may help establish the invasive potential of DCIS. Moreover, this paper indicates that biofluids with low cellularity, such as nipple aspirate fluid and/or ductal lavage, warrant further investigation as early and minimally invasive detection mediums of a cancerization field effect within breast tissue.

  8. Paired Ductal Carcinoma In Situ and Invasive Breast Cancer Lesions in the D-Loop of the Mitochondrial Genome Indicate a Cancerization Field Effect

    Directory of Open Access Journals (Sweden)

    Andrea Maggrah

    2013-01-01

    Full Text Available Alterations in the mitochondrial genome have been chronicled in most solid tumors, including breast cancer. The intent of this paper is to compare and document somatic mitochondrial D-loop mutations in paired samples of ductal carcinoma in situ (DCIS and invasive breast cancer (IBC indicating a potential breast ductal epithelial cancerization field effect. Paired samples of these histopathologies were laser-captured microdissected (LCM from biopsy, lumpectomy, and mastectomy tissues. Blood samples were collected as germplasm control references. For each patient, hypervariable region 1 (HV1 in the D-loop portion of the mitochondrial genome (mtGenome was sequenced for all 3 clinical samples. Specific parallel somatic heteroplasmic alterations between these histopathologies, particularly at sites 16189, 16223, 16224, 16270, and 16291, suggest the presence of an epithelial, mitochondrial cancerization field effect. These results indicate that further characterization of the mutational pathway of DCIS and IBC may help establish the invasive potential of DCIS. Moreover, this paper indicates that biofluids with low cellularity, such as nipple aspirate fluid and/or ductal lavage, warrant further investigation as early and minimally invasive detection mediums of a cancerization field effect within breast tissue.

  9. 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.

  10. Postoperative CMF Does Not Ameliorate Poor Outcomes in Women With Residual Invasive Breast Cancer After Neoadjuvant Epirubicin/Docetaxel Chemotherapy.

    Science.gov (United States)

    Promberger, Regina; Dubsky, Peter; Mittlböck, Martina; Ott, Johannes; Singer, Christian; Seemann, Rudolf; Exner, Ruth; Panhofer, Peter; Steger, Günther; Bergen, Elisabeth; Gnant, Michael; Jakesz, Raimund; Bago-Horvath, Zsuzsanna; Rudas, Margaretha; Bartsch, Rupert

    2015-12-01

    Neoadjuvant chemotherapy (NACT) is an accepted treatment approach in early-stage breast cancer. In contrast, the potential role of postneoadjuvant chemotherapy after taxane-containing NACT remains unclear. The aim of this study was to evaluate postneoadjuvant chemotherapy and further prognostic factors that predict outcome in women without pathologic complete remission (pCR). A total of 377 patients with breast cancer who received preoperative chemotherapy were included in this retrospective study. Patients without standard NACT (6 cycles of epirubicin with docetaxel) or primary metastatic breast cancer and locally advanced, inoperable cancer were excluded from further analysis (n = 186). This resulted in a study population of 191 women (30 [15.7%] with pCR; 161 [84.3%] without pCR). Major outcome parameters were event-free survival (EFS) and overall survival (OS). The following parameters were tested for their prognostic role: postneoadjuvant chemotherapy, patient age, breast cancer subtype (luminal/HER2-negative tumors, HER2-positive tumors, and triple-negative tumors), histological grade, pCR, residual lymph node invasion, and residual invasive tumor size. At a median follow-up of 54 months, 51 disease relapses (26.7%) and 21 deaths (11%) were observed. In a comparison of patients with pCR with those without, no significant differences in EFS or OS were observed. Postneoadjuvant chemotherapy was significantly associated with shorter OS in patients without pCR. In this population, which included a high percentage of patients with luminal cancers, pCR did not predict for improved OS. Postneoadjuvant chemotherapy showed no discernible benefit even in subgroups with aggressive tumor biology or significant remaining tumor burden. The use of such treatment should therefore be discouraged outside of clinical trials. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. 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...

  12. 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

  13. Breast cancer statistics, 2013.

    Science.gov (United States)

    DeSantis, Carol; Ma, Jiemin; Bryan, Leah; Jemal, Ahmedin

    2014-01-01

    In this article, the American Cancer Society provides an overview of female breast cancer statistics in the United States, including data on incidence, mortality, survival, and screening. Approximately 232,340 new cases of invasive breast cancer and 39,620 breast cancer deaths are expected to occur among US women in 2013. One in 8 women in the United States will develop breast cancer in her lifetime. Breast cancer incidence rates increased slightly among African American women; decreased among Hispanic women; and were stable among whites, Asian Americans/Pacific Islanders, and American Indians/Alaska Natives from 2006 to 2010. Historically, white women have had the highest breast cancer incidence rates among women aged 40 years and older; however, incidence rates are converging among white and African American women, particularly among women aged 50 years to 59 years. Incidence rates increased for estrogen receptor-positive breast cancers in the youngest white women, Hispanic women aged 60 years to 69 years, and all but the oldest African American women. In contrast, estrogen receptor-negative breast cancers declined among most age and racial/ethnic groups. These divergent trends may reflect etiologic heterogeneity and the differing effects of some factors, such as obesity and parity, on risk by tumor subtype. Since 1990, breast cancer death rates have dropped by 34% and this decrease was evident in all racial/ethnic groups except American Indians/Alaska Natives. Nevertheless, survival disparities persist by race/ethnicity, with African American women having the poorest breast cancer survival of any racial/ethnic group. Continued progress in the control of breast cancer will require sustained and increased efforts to provide high-quality screening, diagnosis, and treatment to all segments of the population. © 2013 American Cancer Society, Inc.

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

    OpenAIRE

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

    2009-01-01

    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 ...

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

    Science.gov (United States)

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

    2017-05-01

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

  16. Triple-negative invasive breast cancer on dynamic contrast-enhanced and diffusion-weighted MR imaging: comparison with other breast cancer subtypes

    Energy Technology Data Exchange (ETDEWEB)

    Youk, Ji Hyun; Son, Eun Ju; Chung, Jin; Kim, Jeong-Ah; Kim, Eun-kyung [Department of Radiology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2012-08-15

    To determine the MRI features of triple-negative invasive breast cancer (TNBC) on dynamic contrast-enhanced MR imaging (DCE-MRI) and diffusion-weighted MR imaging (DWI) in comparison with ER-positive/HER2-negative (ER+) and HER2-positive cancer (HER2+). A total of 271 invasive cancers in 269 patients undergoing preoperative MRI and surgery were included. Two radiologists retrospectively assessed morphological and kinetic characteristics on DCE-MRI and tumour detectability on DWI. Apparent diffusion coefficient (ADC) values of lesions were measured. Clinical and MRI features of the three subtypes were compared. Compared with ER+ (n = 119) and HER2+ (n = 94), larger size, round/oval mass shape, smooth mass margin, and rim enhancement on DCE-MRI were significantly associated with TNBC (n = 58; P < 0.0001). On DWI, mean ADC value (x 10{sup -3} mm{sup 2}/s) of TNBC (1.03) was higher than the mean ADC values for ER+ and HER2+ (0.89 and 0.84; P < 0.0001). There was no difference in tumour detectability (P = 0.099). Tumour size (P = 0.009), mass margin (smooth, P < 0.0001; irregular, P = 0.020), and ADC values (P = 0.002) on DCE-MRI and DWI were independent features of TNBC. In addition to the morphological features, higher ADC values on DWI were independently associated with TNBC and could be useful in differentiating TNBC from ER+ and HER2+. (orig.)

  17. 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.

  18. MicroRNA-340 inhibits the migration, invasion, and metastasis of breast cancer cells by targeting Wnt pathway.

    Science.gov (United States)

    Mohammadi-Yeganeh, Samira; Paryan, Mahdi; Arefian, Ehsan; Vasei, Mohammad; Ghanbarian, Hossein; Mahdian, Reza; Karimipoor, Morteza; Soleimani, Masoud

    2016-07-01

    MicroRNAs (miRNAs) play a key role in tumor metastasis based on their capacity to regulate the expression of tumor-related genes. Over-expression of key genes such as c-MYC and CTNNB1 (encoding β-catenin) in Wnt/β-catenin-dependent and ROCK1 in Wnt/β-catenin-independent signaling pathways (Rho/Rho-associated kinase (ROCK) signaling pathway) has already been identified as the hallmarks of many tumors, and their role in breast cancer has also been investigated and confirmed. miR-340 characterization as an onco-suppressor miRNA has been previously reported. However, the mechanism by which it inhibits metastasis has not been completely elucidated. Quantitative real-time PCR (qPCR), Western blot, and luciferase assays were used to confirm the effect of miR-340 on the 3'-untranslated region (UTR) of the target genes. Lentiviral particles containing miR-340 were also used to evaluate the effect of miR-340 restoration on cell proliferation, migration, and invasion in vitro in the invasive MDA-MB-231 cell line. By applying bioinformatic approaches for the prediction of miRNAs targeting 3'-UTRs of CTNNB1, c-MYC, and ROCK1, we found out that miR-340 could dramatically down-regulate metastasis by targeting Wnt signaling in breast cancer cells. In the current study, analyzing miR-340 by reverse transcription quantitative PCR (RT-qPCR) in MDA-MB-231 showed that it was remarkably down-regulated in the metastatic breast cancer cell line. We found that restoration of miR-340 in the invasive breast cancer cell line, MDA-MB-231, suppresses the expression of the target genes' messenger RNA (mRNA) and protein and, as a result, inhibits tumor cell invasion and metastasis. Our findings highlight the ability of bioinformatic approaches to find miRNAs targeting specific genes. By bioinformatic analysis, we confirmed the important role of miR-340 as a pivotal regulator of breast cancer metastasis in targeting previously validated (ROCK1) and potentially novel genes, i.e., (CTNNB1 and c-MYC).

  19. Breast cancer in situ. From pre-malignant lesion of uncertain significance to well-defined non-invasive malignant lesion

    DEFF Research Database (Denmark)

    Laenkholm, Anne-Vibeke; Jensen, Maj-Britt; Kroman, Niels

    2008-01-01

    In addition to nationwide standardized pathology forms for operable primary invasive breast cancer, the Danish Breast Cancer cooperative Group (DBCG) in 1982 introduced pathology forms for breast cancer in situ (CIS). The histological reporting form was used primarily for ductal cancer in situ...... receptor (ER) and Progesteron receptor (PR) status. Also mastectomy specimens were included. In 2004 the previous malignancy grading was replaced by the Van Nuys classification, and information on microcalcifications was introduced. The axillary status now included the sentinel node technique only. In 2006...

  20. 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...... as effectors of ErbB2-induced invasion in vitro. We identify Cdc42-binding protein kinase beta, extracellular regulated kinase 2, p21-activated protein kinase 4, and protein kinase C alpha as essential mediators of ErbB2-induced cysteine cathepsin expression and breast cancer cell invasiveness. The identified...

  1. 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

    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. 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. 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 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 associated with breast density.

  2. miR-217 inhibits triple-negative breast cancer cell growth, migration, and invasion through targeting KLF5.

    Directory of Open Access Journals (Sweden)

    Wenhui Zhou

    Full Text Available Triple negative breast cancer (TNBC is one of the most aggressive breast cancers without effective targeted therapies. Numerous studies have implied that KLF5 plays an important roles in TNBC. How is KLF5 regulated by microRNAs has not been well studied. Here, we demonstrated that miR-217 down-regulates the expression of KLF5 and KLF5's downstream target gene FGF-BP and Cyclin D1 in TNBC cell lines HCC1806 and HCC1937. Consequently, miR-217 suppresses TNBC cell growth, migration, and invasion. MiR-217 suppresses TNBC, at least partially, through down-regulating the KLF5 expression. These results suggest that the miR-217-KLF5 axis might serve as a potential target for treatment of TNBC.

  3. 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.

  4. Cytokines, Neovascularization and Breast Cancer

    Science.gov (United States)

    1996-10-01

    Rationale Angiogenesis is important in the growth and metastases of human breast cancer . We hypothesize that this process is under the control of...staining patern seen in invasive cancer , in situ cancer , and benign breast tissue. Note that staining was graded as the most intensly staining area. The...blocked, tumors do not grow or metastasize . The purpose of this study was to demonstrate that breast cancer cells are capable of participating in this

  5. 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.

  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. Breast cancer

    CERN Multimedia

    2002-01-01

    "Cancer specialists will soon be able to compare mammograms with computerized images of breast cancer from across Europe, in a bid to improve diagnosis and treatment....The new project, known as MammoGrid, brings together computer and medical imaging experts, cancer specialists, radiologists and epidemiologists from Bristol, Oxford, Cambridge, France and Italy" (1 page).

  8. BSP gene silencing inhibits migration, invasion, and bone metastasis of MDA-MB-231BO human breast cancer cells.

    Directory of Open Access Journals (Sweden)

    Jie Wang

    Full Text Available Bone sialoprotein (BSP has been implicated in a variety of physiological and pathophysiological events, including tumor cell invasion, bone homing, adhesion, and matrix degradation. To explore the potential involvement of BSP in human breast cancer cell invasion and metastasis, we used retrovirus-mediated RNAi to deplete BSP levels in the human bone-seeking breast cancer cell line MDA-MB-231BO (231BO and established the 231BO-BSP27 and 231BO-BSP81 cell clones. Cell proliferation, colony formation, wound healing, and the ability to invade into matrigel of these BSP-depleted clones were all decreased. Both 231BO-BSP27 cells and 231BO-BSP81 cells showed a significant (15.4% and 28.6% respectively reduction of bone metastatic potential following intracardiac injection as determined by X-ray detection and by hematoxylin and eosin staining. Moreover, the expression of integrins αvβ3 and β3 was decreased in the BSP-silenced cells whereas ectopic BSP expression increased the integrins αvβ3 and β3 levels. These results together suggest that BSP silencing decreased the integrin αvβ3 and β3 levels, in turn inhibiting cell migration and invasion and decreasing the ability of the cells to metastasize to bone.

  9. 6 Common Cancers - Breast Cancer

    Science.gov (United States)

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

  10. Breast Cancer

    Science.gov (United States)

    ... a reduced risk of breast cancer. The Mediterranean diet focuses mostly on plant-based foods, such as fruits and vegetables, whole grains, legumes, and nuts. People who follow the Mediterranean diet choose healthy fats, such as olive oil, over ...

  11. Breast Cancer

    Science.gov (United States)

    ... disease. It’s estimated that about 10% of breast cancer cases are hereditary (run in the family). In many of these cases, you inherited a gene from your parents that has mutated (changed from ...

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

    Science.gov (United States)

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

    2015-10-01

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

  13. High Prevalence of MRI-Detected Contralateral and Ipsilateral Malignant Findings in Patients With Invasive Ductolobular Breast Cancer : Impact on Surgical Management

    NARCIS (Netherlands)

    El Sharouni, Mary Ann; Postma, Emily L; Menezes, Gisela L G|info:eu-repo/dai/nl/413920763; van den Bosch, Maurice A A J|info:eu-repo/dai/nl/182981630; Pijnappel, Ruud M.|info:eu-repo/dai/nl/239429583; Witkamp, Arjen J.|info:eu-repo/dai/nl/245008780; van der Pol, Carmen C.|info:eu-repo/dai/nl/41397006X; Verkooijen, Helena M.|info:eu-repo/dai/nl/213707705; van Diest, Paul J.|info:eu-repo/dai/nl/075281775

    2016-01-01

    INTRODUCTION: Invasive breast cancer comprises a spectrum of histologic changes with purely lobular and purely ductal cancer on either side and mixed lesions in between. Our aim was to evaluate to what extent preoperative magnetic resonance imaging (MRI) leads to the finding of additional

  14. 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.

  15. Phosphorylation of calcium/calmodulin-stimulated protein kinase II at T286 enhances invasion and migration of human breast cancer cells.

    Science.gov (United States)

    Chi, Mengna; Evans, Hamish; Gilchrist, Jackson; Mayhew, Jack; Hoffman, Alexander; Pearsall, Elizabeth Ann; Jankowski, Helen; Brzozowski, Joshua Stephen; Skelding, Kathryn Anne

    2016-09-08

    Calcium/calmodulin-stimulated protein kinase II (CaMKII) is a multi-functional kinase that controls a range of cellular functions, including proliferation, differentiation and apoptosis. The biological properties of CaMKII are regulated by multi-site phosphorylation. However, the role that CaMKII phosphorylation plays in cancer cell metastasis has not been examined. We demonstrate herein that CaMKII expression and phosphorylation at T286 is increased in breast cancer when compared to normal breast tissue, and that increased CAMK2 mRNA is associated with poor breast cancer patient prognosis (worse overall and distant metastasis free survival). Additionally, we show that overexpression of WT, T286D and T286V forms of CaMKII in MDA-MB-231 and MCF-7 breast cancer cells increases invasion, migration and anchorage independent growth, and that overexpression of the T286D phosphomimic leads to a further increase in the invasive, migratory and anchorage independent growth capacity of these cells. Pharmacological inhibition of CaMKII decreases MDA-MB-231 migration and invasion. Furthermore, we demonstrate that overexpression of T286D, but not WT or T286V-CaMKII, leads to phosphorylation of FAK, STAT5a, and Akt. These results demonstrate a novel function for phosphorylation of CaMKII at T286 in the control of breast cancer metastasis, offering a promising target for the development of therapeutics to prevent breast cancer metastasis.

  16. Interactions between αv-Integrin and HER2 and Their Role in the Invasive Phenotype of Breast Cancer Cells In Vitro and in Rat Brain.

    Science.gov (United States)

    Lal, Sangeet; Kersch, Cymon; Beeson, Kathleen A; Wu, Y Jeffrey; Muldoon, Leslie L; Neuwelt, Edward A

    2015-01-01

    We tested the hypothesis that αv-integrin and the human epidermal growth factor receptor type 2 (HER2) interact with each other in brain trophic metastatic breast cancer cells and influence their invasive phenotype. Clones of MDA-MB231BR human breast cancer cells with stable knock down of αv-integrin in combination with high or low levels of HER2 were created. The interactions of these two proteins and their combined effect on cell migration and invasion were investigated in vitro and in vivo. Knockdown of αv-integrin in MDA-MB231BR clones altered the actin cytoskeleton and cell morphology. HER2 co-precipitated with αv-integrin in three breast cancer cell lines in vitro, suggesting they complex in cells. Knockdown of αv-integrin altered HER2 localization from its normal membrane position to a predominantly lysosomal localization. When αv-integrin expression was decreased by 69-93% in HER2-expressing cells, cellular motility was significantly reduced. Deficiency of both αv-integrin and HER2 decreased cellular migration and invasion by almost 90% compared to cells expressing both proteins (Pcancer cells and may regulate HER2 localization. The combined impacts of αv-integrin and HER2 influence the invasive phenotype of breast cancer cells. Targeting αv-integrin in HER2-positive breast cancer may slow growth and decrease infiltration in the normal brain.

  17. Induction of discrete apoptotic pathways by bromo-substituted indirubin derivatives in invasive breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Nicolaou, Katerina A. [Department of Biological Sciences, University of Cyprus, Nicosia (Cyprus); Liapis, Vasilis; Evdokiou, Andreas [Department of Surgery, Basil Hetzel Institute, Adelaide University, Adelaide (Australia); Constantinou, Constantina [St. George' s University of London Medical School at the University of Nicosia, Nicosia (Cyprus); Magiatis, Prokopios; Skaltsounis, Alex L. [Faculty of Pharmacy, University of Athens, Athens (Greece); Koumas, Laura; Costeas, Paul A. [Center for Study of Hematological Malignancies, Nicosia (Cyprus); Constantinou, Andreas I., E-mail: andreasc@ucy.ac.cy [Department of Biological Sciences, University of Cyprus, Nicosia (Cyprus)

    2012-08-17

    Highlights: Black-Right-Pointing-Pointer The effects of 6BIO and 7BIO are evaluated against five breast cancer cell lines. Black-Right-Pointing-Pointer 6BIO induces a caspase dependent apoptotic effect via the intrinsic pathway. Black-Right-Pointing-Pointer 7BIO promotes G{sub 2}/M cells cycle arrest. Black-Right-Pointing-Pointer 7BIO triggers a caspase-8 mediated apoptotic pathway. Black-Right-Pointing-Pointer 7BIO triggers and a caspase independent pathway. -- Abstract: Indirubin derivatives gained interest in recent years for their anticancer and antimetastatic properties. The objective of the present study was to evaluate and compare the anticancer properties of the two novel bromo-substituted derivatives 6-bromoindirubin-3 Prime -oxime (6BIO) and 7-bromoindirubin-3 Prime -oxime (7BIO) in five different breast cancer cell lines. Cell viability assays identified that 6BIO and 7BIO are most effective in preventing the proliferation of the MDA-MB-231-TXSA breast cancer cell line from a total of five breast cancer cell lined examined. In addition it was found that the two compounds induce apoptosis via different mechanisms. 6BIO induces caspase-dependent programmed cell death through the intrinsic (mitochondrial) caspase-9 pathway. 7BIO up-regulates p21 and promotes G{sub 2}/M cell cycle arrest which is subsequently followed by the activation of two different apoptotic pathways: (a) a pathway that involves the upregulation of DR4/DR5 and activation of caspase-8 and (b) a caspase independent pathway. In conclusion, this study provides important insights regarding the molecular pathways leading to cell cycle arrest and apoptosis by two indirubin derivatives that can find clinical applications in targeted cancer therapeutics.

  18. Effects of alpha-difluoromethylornithine on markers of proliferation, invasion, and apoptosis in breast cancer.

    Science.gov (United States)

    Izbicka, Elzbieta; Streeper, Robert T; Yeh, I-Tien; Pressley, Oredius; Grant, Michael; Andrews, J Valerie R; Kuhn, Joseph; O'Shaughnessy, Joyce

    2010-06-01

    To examine changes in biomarkers expressed in breast tumors in response to patient treatment with the polyamine synthesis inhibitor alpha-difluoromethylornithine (DFMO). The expression of Ki-67 (MIB-1), matrix metalloproteinases (MMP) 2 and 9, urokinase-type plasminogen activator (uPA) were examined by immunohistochemistry in breast tissue specimens (controls: n=15, 13 evaluable, and DFMO group; n=27, 21 evaluable). Apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL). Significant increases in apoptosis, MMP-9 and uPA (tumor) were observed in 7 patients >or=50 years who received DFMO for >or=14 days relative to patients <50 years and/or who received <14 days of treatment (n=11). No other measured characteristics, including tumor estrogen and progesterone receptor status, hormone replacement therapy history, histopathological characteristics or tumor grade were correlated with these biomarker changes. Unexpected correlation of proapoptotic DFMO activity in postmenopausal women with breast cancer warrants further study.

  19. 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.

  20. Novel circulating microRNA signature as a potential non-invasive multi-marker test in ER-positive early-stage breast cancer

    DEFF Research Database (Denmark)

    Kodahl, Annette R; Lyng, Maria Bibi; Binder, Harald

    2014-01-01

    INTRODUCTION: There are currently no highly sensitive and specific minimally invasive biomarkers for detection of early-stage breast cancer. MicroRNAs (miRNAs) are present in the circulation and may be unique biomarkers for early diagnosis of human cancers. The aim of this study was to investigate......RNA signature to stratify samples from breast cancer patients and healthy controls was confirmed in the validation set (p = 0.012) with a corresponding AUC = 0.665 in the ROC-curve analysis. No association between miRNA expression and tumor grade, tumor size, menopausal- or lymph node status was observed....... The signature was also successfully validated in a previously published independent data set of circulating miRNAs in early-stage breast cancer (p = 0.024). CONCLUSIONS: We present herein a 9 miRNA signature capable of discriminating between ER-positive breast cancer and healthy controls. Using a specific...

  1. Risks of Breast Cancer Screening

    Science.gov (United States)

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

  2. Suppression of Invasion and Metastasis of Triple-Negative Breast Cancer Lines by Pharmacological or Genetic Inhibition of Slug Activity

    Directory of Open Access Journals (Sweden)

    Giovanna Ferrari-Amorotti

    2014-12-01

    Full Text Available Most triple-negative breast cancers (TNBCs exhibit gene expression patterns associated with epithelial-to-mesenchymal transition (EMT, a feature that correlates with a propensity for metastatic spread. Overexpression of the EMT regulator Slug is detected in basal and mesenchymal-type TNBCs and is associated with reduced E-cadherin expression and aggressive disease. The effects of Slug depend, in part, on the interaction of its N-terminal SNAG repressor domain with the chromatin-modifying protein lysine demethylase 1 (LSD1; thus, we investigated whether tranylcypromine [also known as trans-2-phenylcyclopropylamine hydrochloride (PCPA or Parnate], an inhibitor of LSD1 that blocks its interaction with Slug, suppresses the migration, invasion, and metastatic spread of TNBC cell lines. We show here that PCPA treatment induces the expression of E-cadherin and other epithelial markers and markedly suppresses migration and invasion of TNBC cell lines MDA-MB-231 and BT-549. These effects were phenocopied by Slug or LSD1 silencing. In two models of orthotopic breast cancer, PCPA treatment reduced local tumor growth and the number of lung metastases. In mice injected directly in the blood circulation with MDA-MB-231 cells, PCPA treatment or Slug silencing markedly inhibited bone metastases but had no effect on lung infiltration. Thus, blocking Slug activity may suppress the metastatic spread of TNBC and, perhaps, specifically inhibit homing/colonization to the bone.

  3. Rap2B promotes proliferation, migration, and invasion of human breast cancer through calcium-related ERK1/2 signaling pathway.

    Science.gov (United States)

    Di, Jiehui; Huang, Hui; Qu, Debao; Tang, Juangjuan; Cao, Wenjia; Lu, Zheng; Cheng, Qian; Yang, Jing; Bai, Jin; Zhang, Yanping; Zheng, Junnian

    2015-07-23

    Rap2B, a member of GTP-binding proteins, is widely upregulated in many types of tumors and promotes migration and invasion of human suprarenal epithelioma. However, the function of Rap2B in breast cancer is unknown. Expression of Rap2B was examined in breast cancer cell lines and human normal breast cell line using Western blot analysis. Using the CCK-8 cell proliferation assay, cell cycle analysis, and transwell migration assay, we also elucidated the role of Rap2B in breast cancer cell proliferation, migration, and invasion. Results showed that the expression of Rap2B is higher in tumor cells than in normal cells. Flow cytometry and Western blot analysis revealed that Rap2B elevates the intracellular calcium level and further promotes extracellular signal-related kinase (ERK) 1/2 phosphorylation. By contrast, calcium chelator BAPTM/AM and MEK inhibitor (U0126) can reverse Rap2B-induced ERK1/2 phosphorylation. Furthermore, Rap2B knockdown inhibits cell proliferation, migration, and invasion abilities via calcium related-ERK1/2 signaling. In addition, overexpression of Rap2B promotes cell proliferation, migration and invasion abilities, which could be neutralized by BAPTM/AM and U0126. Taken together, these findings shed light on Rap2B as a therapeutic target for breast cancer.

  4. Danish Breast Cancer Cooperative Group

    DEFF Research Database (Denmark)

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

    2016-01-01

    AIM OF DATABASE: Danish Breast Cancer Cooperative Group (DBCG), with an associated database, was introduced as a nationwide multidisciplinary group in 1977 with the ultimate aim to improve the prognosis in breast cancer. Since then, the database has registered women diagnosed with primary invasive...

  5. Epidemiology of Breast Cancer

    OpenAIRE

    南, 優子; ミナミ, ユウコ; MINAMI, Yuko

    2007-01-01

    During recent decades, breast cancer incidence has been increasing in Japan. Epidemiological studies have clarified the trend in breast cancer incidence and identified risk factors for breast cancer. Established risk factors for breast cancer include early age at menarche, late age at first birth, low parity, postmenopausal obesity, family history of breast cancer, and history of benign breast disease. Breast-feeding and physical activity may also be associated with breast cancer risk. Detail...

  6. 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.

  7. 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

  8. 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

  9. 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.

  10. 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.

  11. miR-409-3p suppresses breast cancer cell growth and invasion by targeting Akt1

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Guoqiang [Department of Breast Surgery, Qilu Hospital, Shandong University, Jinan 250012 (China); Department of Thyroid and Breast Surgery, Hospital Affiliated to Binzhou Medical University, 661 Second Huanghe Street, Binzhou 256603 (China); Liu, Zengyan [Department of Hematology, Hospital Affiliated to Binzhou Medical University, 661 Second Huanghe Street, Binzhou 256603 (China); Xu, Hao [Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029 (China); Yang, Qifeng, E-mail: qifengy_sdu1@163.com [Department of Breast Surgery, Qilu Hospital, Shandong University, Jinan 250012 (China)

    2016-01-08

    Altered levels and functions of microRNAs (miRNAs) are correlated with carcinogenesis. While miR-409-3p has been shown to play important roles in several cancer types, its function in the context of breast cancer (BC) remains unknown. In this study, miR-409-3p was significantly downregulated in BC tissues and cell lines, compared with the corresponding control counterparts. Overexpression of miR-409-3p inhibited BC cell proliferation, migration and invasion in vitro and suppressed tumor growth in vivo. Notably, miR-409-3p induced downregulation of Akt1 protein through binding to its 3′ untranslated region (UTR). Conversely, restoring Akt1 expression rescued the suppressive effects of miR-409-3p. Our data collectively indicate that miR-409-3p functions as a tumor suppressor in BC through downregulating Akt1, supporting the targeting of the novel miR-409-3p/Akt1 axis as a potentially effective therapeutic approach for BC. - Highlights: • miR-409-3p inhibits proliferation, migration and invasion of BC cells. • miR-409-3p suppresses tumor growth in nude mice. • Akt1 is a direct downstream target of miR-409-3p. • Ectopic expression of Akt1 reverses the effects of miR-409-3p on cell proliferation, migration and invasion.

  12. Genetic clonal mapping of in situ and invasive ductal carcinoma indicates the field cancerization phenomenon in the breast.

    Science.gov (United States)

    Foschini, Maria P; Morandi, Luca; Leonardi, Elisa; Flamminio, Federica; Ishikawa, Yuko; Masetti, Riccardo; Eusebi, Vincenzo

    2013-07-01

    Nearly 80% of well-differentiated in situ duct carcinomas (g1 DCIS) have been shown to be multicentric (multilobar) lesions, while most in situ poorly differentiated duct carcinomas (g3 DCIS) were unifocal (unilobar) lesions. Here we present a clonality study of 15 cases of DCIS, all showing multiple foci. Twelve of these cases were associated with an invasive duct carcinoma. Fifteen cases of female breast cancer patients all showing multiple DCIS foci (5 g1 DCIS, 5 g2 DCIS, 5 g3 DCIS) were randomly selected and histologically studied using large histological sections. Care was taken to laser-microdissect DCIS foci that were most distantly located from one another in the same large section, and pertinent cells were genetically studied. Invasive duct carcinoma and ipsilateral lymph node metastases and/or contralateral lesions, whenever present, were additionally microdissected. DNA of neoplastic cells was purified, and the mtDNA D-loop region was sequenced. Genetic distance of different foci from the same case was visualized by phylogenetic analyses using the neighbor-joining method. Patients ranged in age from 36 to 87 years (mean 65.1). All 9 cases of widely spread DCIS were not clonal. Four of 6 cases that showed multiple adjacent foci were clonally related on mtDNA analysis. In the present series, 11/15 DCIS appeared as multiple synchronous primary breast tumors, genetically not related to one another. The present data enhance the view that breast can also show the field cancerization phenomenon, paralleling what has already been proposed in other organs. Copyright © 2013 Elsevier Inc. All rights reserved.

  13. 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

  14. 10-Gingerol inhibits proliferation and invasion of MDA-MB-231 breast cancer cells through suppression of Akt and p38MAPK activity.

    Science.gov (United States)

    Joo, Ji-Hye; Hong, Seong-Su; Cho, Young-Rak; Seo, Dong-Wan

    2016-02-01

    In the present study, we investigated the roles and molecular mechanism of 10-gingerol, a phenolic compound isolated from Zingiber officinale, in regulating cell proliferation and invasion of MDA‑MB‑231 breast cancer cells. 10-gingerol treatment inhibited cell proliferation through downregulation of cell cycle regulatory proteins such as cyclin-dependent kinases and cyclins, and subsequent induction of G1 phase arrest. In addition, 10‑gingerol treatment blocked cell invasion in response to mitogenic stimulation. These antitumor activities of 10‑gingerol were mediated through inactivation of Akt and p38MAPK activity, and suppression of epidermal growth factor receptor expression. Collectively, these findings demonstrate the pharmacological roles of 10-gingerol in regulating breast cancer cell growth and progression, and suggest further evaluation and development as a potential therapeutic agent for the prevention and treatment of breast cancer.

  15. Novel Function of NIBP in Breast Cancer

    Science.gov (United States)

    2012-05-01

    histologically diagnosed as invasive ductal carcinoma , 21 (7.1%) have invasive lobular carcinoma and 11 (3.8%) suffered other types of breast cancer. The...understand the molecular mechanisms for NIBP/NFB signaling in cancer cells that play a pivotal role in promoting tumor development and invasion . The...tumor formation and metastatic invasion of breast cancer cells. We anticipate that overexpression of NIBP may promote the proliferation and survival

  16. [Pregnancy and breast cancer].

    Science.gov (United States)

    Ramírez-Torres, Nicolás; Asbun-Bojalil, Juan; Hernández-Valencia, Marcelino

    2013-01-01

    association of breast cancer and pregnancy is not common. The objective of this investigation was to evaluate the pregnancy, young age, stage, treatment, prognosis and mortality of women with breast cancer during pregnancy. retrospective analysis from March 1992 to February 2009, 16 patients were included with breast cancer and pregnancy. They were analized: histological characteristic of tumor, therapeutic response of the oncological treatment, evolution of the pregnancy. From of baby born: Apgar and weight. The woman's mortality with breast cancer during pregnancy was evaluated for age group and for interval of time between late pregnancy and diagnosis posterior of breast cancer and pregnancy. characteristic predominant clinicohistological: stage III (81.2%), T3-T4 (75%), N+ 93.7%, invasive ductal carcinoma (87.5%), histological grade 2-3 (93.7%), receptor estrogeno positive (43.7%); RPpositive (25%); HER-2/neu positive (31.2%). 27 chemotherapy cycles were applied with 5-fluorouracil, epirubicin and cyclophosphamide during the second or third trimester of the pregnancy, there were not severe adverse effects for the mothers and the baby born exposed to chemotherapy. The mean time to disease recurrence was 18.8 months (range, 6-62 months). The rate of mortality for specific age (breast cancer and pregnancy.

  17. Basal Subtype of Invasive Breast Cancer Is Associated With a Higher Risk of True Recurrence After Conventional Breast-Conserving Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Hattangadi-Gluth, Jona A. [Harvard Radiation Oncology Program, Boston, Massachusetts (United States); Wo, Jennifer Y. [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Nguyen, Paul L. [Department of Radiation Oncology, Dana-Farber Cancer Institute/Brigham and Women' s Hospital, Boston, Massachusetts (United States); Abi Raad, Rita F. [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Sreedhara, Meera [Department of Radiation Oncology, Dana-Farber Cancer Institute/Brigham and Women' s Hospital, Boston, Massachusetts (United States); Niemierko, Andrzej [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Freer, Phoebe E. [Department of Radiology, Massachusetts General Hospital, Boston, Massachusetts (United States); Georgian-Smith, Dianne [Department of Radiology, Brigham and Women' s Hospital, Boston, Massachusetts (United States); Bellon, Jennifer R.; Wong, Julia S. [Department of Radiation Oncology, Dana-Farber Cancer Institute/Brigham and Women' s Hospital, Boston, Massachusetts (United States); Smith, Barbara L. [Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts (United States); Harris, Jay R. [Department of Radiation Oncology, Dana-Farber Cancer Institute/Brigham and Women' s Hospital, Boston, Massachusetts (United States); Taghian, Alphonse G., E-mail: ataghian@partners.org [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States)

    2012-03-01

    Purpose: To determine whether breast cancer subtype is associated with patterns of ipsilateral breast tumor recurrence (IBTR), either true recurrence (TR) or elsewhere local recurrence (ELR), among women with pT1-T2 invasive breast cancer (IBC) who receive breast-conserving therapy (BCT). Methods and Materials: From Jan 1998 to Dec 2003, 1,223 women with pT1-T2N0-3 IBC were treated with BCT (lumpectomy plus whole-breast radiation). Ninety percent of patients received adjuvant systemic therapy, but none received trastuzumab. Biologic cancer subtypes were approximated by determining estrogen receptor-positive (ER+), progesterone receptor-positive (PR+), and human epidermal growth factor receptor-2-positive (HER-2+) expression, classified as luminal A (ER+ or PR+ and HER-2 negative [HER-2-]), luminal B (ER+ or PR+ and HER-2+), HER-2 (ER- and PR- and HER-2+), and basal (ER- and PR- and HER-2- ) subtypes. Imaging, pathology, and operative reports were reviewed by two physicians independently, including an attending breast radiologist. Readers were blinded to subtype and outcome. TR was defined as IBTR within the same quadrant and within 3 cm of the primary tumor. All others were defined as ELR. Results: At a median follow-up of 70 months, 24 patients developed IBTR (5-year cumulative incidence of 1.6%), including 15 TR and 9 ELR patients. At 5 years, basal (4.4%) and HER-2 (9%) subtypes had a significantly higher incidence of TR than luminal B (1.2%) and luminal A (0.2%) subtypes (p < 0.0001). On multivariate analysis, basal subtype (hazard ratio [HR], 4.8, p = 0.01), younger age at diagnosis (HR, 0.97; p = 0.05), and increasing tumor size (HR, 2.1; p = 0.04) were independent predictors of TR. Only younger age (HR, 0.95; p = 0.01) significantly predicted for ELR. Conclusions: Basal and HER-2 subtypes are significantly associated with higher rates of TR among women with pT1-T2 IBC after BCT. Younger age predicts for both TR and ELR. Strategies to reduce TR in basal

  18. Identification of Genetic Markers of the Invasive Phenotype in Human Breast Cancer

    Science.gov (United States)

    2000-10-01

    image analysis, using MCID tional positive control MDA-MB-231 human breast cancer M4 software (Imaging Research, ST. Catherine’s, ON). All cells were...tumor sections run with each video image capture and with a MCID -M4 image analysis batch. Levels were scored semiquantitatively as previ- program...oestrogen receptor prior to quantitation by video-image analysis and (ER) levels (three ER ᝺ fmol/mg, three ER 10-20, densitometry using an MCID M4 system

  19. Early Adoption of the SSO-ASTRO Consensus Guidelines on Margins for Breast-Conserving Surgery with Whole-Breast Irradiation in Stage I and II Invasive Breast Cancer: Initial Experience from Memorial Sloan Kettering Cancer Center.

    Science.gov (United States)

    Rosenberger, Laura H; Mamtani, Anita; Fuzesi, Sarah; Stempel, Michelle; Eaton, Anne; Morrow, Monica; Gemignani, Mary L

    2016-10-01

    Reexcision rates in patients undergoing breast-conserving surgery (BCS) for early-stage invasive breast cancer are highly variable. The Society of Surgical Oncology (SSO) and American Society for Radiation Oncology (ASTRO) published consensus guidelines to help standardize practice. We sought to determine reexcision rates before and after guideline adoption at our institution. We identified patients with stage I or II invasive breast cancer initially treated with BCS between June 1, 2013, and October 31, 2014. Margins were defined as positive (tumor on ink), close (≤1 mm), or negative (>1 mm), and were recorded for both invasive cancer and ductal carcinoma-in situ (DCIS) components. Reexcision rates were quantified, characteristics were compared between groups, and multivariable logistic regression was performed. A total of 1205 patients were identified, 504 before and 701 after the guideline adoption (January 1, 2014). Clinical and pathologic characteristics were similar between time periods. Reexcision rates significantly declined from 21.4 to 15.1 % (p = 0.006) after guideline adoption. A multivariable model identified extensive intraductal component (odds ratio [OR] 2.5, 95 % confidence interval [CI] 1.2-5.2), multifocality (OR 2.0, 95 % CI 1.2-3.6), positive (OR 844.4, 95 % CI 226.3-5562.5) and close (OR 38.3, 95 % CI 21.5-71.8) ductal carcinoma-in situ margin, positive (OR 174.2, 95 % CI 66.2-530.0) and close (OR 6.4, 95 % CI 3.0-13.6) invasive margin, and time period (OR 0.5, 95 % CI 0.3-0.9 for post vs. pre) as independently associated with reexcision. Overall reexcision rates declined significantly after guideline adoption. Close invasive margins were associated with higher rates of reexcision than negative invasive margins in both time periods; however, the effect diminished in the postguideline adoption period. Thus, we expect continued decline in reexcision rates as adherence to guidelines becomes more uniform.

  20. 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.; 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

  1. Effectiveness of routine visits and routine tests in detecting isolated locoregional recurrences after treatment for early-stage invasive breast cancer : A meta-analysis and systematic review

    NARCIS (Netherlands)

    de Bock, GH; Bonnema, J; van der Hage, J; Kievit, J; van de Velde, CJH

    2004-01-01

    Purpose To review the effectiveness of routine visits and routine tests in detecting isolated locoregional recurrences in asymptomatic patients after treatment for early-stage invasive breast cancer. Methods Systematic review and meta-analysis. The proportion of isolated locoregional recurrences

  2. Breast Cancer Overview

    Science.gov (United States)

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

  3. Breast Cancer -- Male

    Science.gov (United States)

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

  4. 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

    Science.gov (United States)

    Menvielle, Gwenn; Kunst, Anton E.; Van Gils, Carla H.; Peeters, Petra H. M.; 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

    This paper aims to investigate the role of known risk factors in explaining educational differences in breast cancer incidence. Analyses were based on the European Prospective Investigation into Cancer and Nutrition, and included 242,095 women, 433 in situ and 4,469 invasive breast cancers. Reproductive history (age at first full term pregnancy and parity), exposure to endogenous and exogenous hormones, height, and health behaviours were accounted for in the analyses. Relative indices of inequality (RII) for education were estimated using Cox regression models. Higher invasive breast cancer risk was found among women with higher education (RII=1.22: 1.09,1.37). This association was not observed among nulliparous women (RII=1.13: 0.84,1.52). Inequalities in breast cancer incidence decreased substantially after adjusting for reproductive history (RII=1.11: 0.98,1.25), most of the association being explained by age at first full term pregnancy. Each other risk factor explained a small additional part of inequalities in breast cancer incidence. Height contributed most of these factors. When all known risk factors were adjusted for, no association remained between education and invasive breast cancer risk. Inequalities in incidence were more pronounced for in situ breast cancers and remained after adjustment for all known risk factors (RII=1.61: 1.07,2.41), especially among nulliparous women. PMID:21084553

  5. Breast Cancer

    Science.gov (United States)

    ... the Mediterranean diet choose healthy fats, such as olive oil, over butter and fish instead of red meat. Breast cancer risk reduction for women with a high risk If your doctor has assessed your family history and determined that you have other factors, such ...

  6. Silencing of Prrx2 Inhibits the Invasion and Metastasis of Breast Cancer both In Vitro and In Vivo by Reversing Epithelial-Mesenchymal Transition

    Directory of Open Access Journals (Sweden)

    Zhi-Dong Lv

    2017-07-01

    Full Text Available Background/Aims: Epithelial-mesenchymal transition (EMT is recognized as a crucial mechanism in breast cancer progression and metastasis. Paired-related homeobox 2 (Prrx2 has been identified as a new EMT inducer in cancer, but the underlying mechanisms are still poorly understood. Methods: The expression of Prrx2 was assessed by immunohistochemistry in breast cancer tissues to evaluate the clinicopathological significance of Prrx2, as well as the correlation between Prrx2 and EMT. Short hairpin RNA knockdown of Prrx2 was used to examine cellular effects of Prrx2, detecte the expression of Wnt/β-catenin signaling and EMT-associated proteins, and observe cell proliferation, invasion and migration abilities in vitro and in vivo. Results: Clinical association studies showed that Prrx2 expression was related to tumor size, lymph node metastasis, tumor node metastasis stages, EMT and poor survival. Results also showed that knockdown of Prrx2 could alter cell morphology, suppressed the abilities of cell proliferation, invasion and migration in breast cancer. Moreover, silencing of Prrx2 induced the mesenchymal-epithelial transition and prevented nuclear translocation of β-catenin, inhibited wnt/β-catenin signaling pathway. Conclusion: Our study indicated that Prrx2 may be an important activator of EMT in human breast cancer and it can serve as a molecular target of therapeutic interventions for breast cancer.

  7. Morphologic complexity of epithelial architecture for predicting invasive breast cancer survival

    Directory of Open Access Journals (Sweden)

    Tambasco Mauro

    2010-12-01

    Full Text Available Abstract Background Precise criteria for optimal patient selection for adjuvant chemotherapy remain controversial and include subjective components such as tumour morphometry (pathological grade. There is a need to replace subjective criteria with objective measurements to improve risk assessment and therapeutic decisions. We assessed the prognostic value of fractal dimension (an objective measure of morphologic complexity for invasive ductal carcinoma of the breast. Methods We applied fractal analysis to pan-cytokeratin stained tissue microarray (TMA cores derived from 379 patients. Patients were categorized according to low (1.75, N = 90 fractal dimension. Cox proportional-hazards regression was used to assess the relationship between disease-specific and overall survival and fractal dimension, tumour size, grade, nodal status, estrogen receptor status, and HER-2/neu status. Results Patients with higher fractal score had significantly lower disease-specific 10-year survival (25.0%, 56.4%, and 69.4% for high, intermediate, and low fractal dimension, respectively, p Conclusion Except for nodal status, morphologic complexity of breast epithelium as measured quantitatively by fractal dimension was more strongly and significantly associated with disease-specific and overall survival than standard prognosticators.

  8. Inositol hexaphosphate (IP6) inhibits key events of cancer metastasis: I. In vitro studies of adhesion, migration and invasion of MDA-MB 231 human breast cancer cells.

    Science.gov (United States)

    Tantivejkul, Kwanchanit; Vucenik, Ivana; Shamsuddin, Abulkalam M

    2003-01-01

    The anti-cancer agent inositol hexaphosphate (IP6) is an abundant intrinsic component of both plant and mammalian cells. In addition to inducing differentiation and inhibiting growth of numerous cancer cell lines in vitro, IP6 has been demonstrated to prevent and abrogate both primary tumor and metastasis in vivo. Using MDA-MB 231 human breast cancer cells, we studied the potential of IP6 to inhibit cell adhesion, migration and invasion, the key steps in cancer metastasis, utilizing the extracellular matrix (ECM) proteins, a culture wounding assay, modified Boyden chambers, immunocytochemistry and zymography. IP6 treatment caused a 65% reduction of cell adhesion to fibronection (p = 0.002) and a 37% reduction to collagen (p = 0.005). To determine whether a decrease in cell adhesion leads to a decrease in cell motility, migration assays were performed; IP6 decreased both the number of migrating cells and the distance of cell migration into the denuded area by 72% (p < 0.001). Haptotatic cell migration in a modified Boyden chambers was also reduced in a dose-dependent manner. While cell migration on fibronectin was inhibited by 65% (p < 0.001), migration on collagen and laminin was decreased by 32% (p < 0.01) and 13% (p < 0.05), respectively. Immunocytochemistry revealed the absence of lamellipodia structure in IP6-treated cells as compared to untreated cells, corresponding to a diminished ability of cancer cells to form cellular network as determined by Matrigel outgrowth assay. Likewise, cell invasion also was decreased (by 72% after IP6 treatment, p = 0.001) in a dose-dependent fashion. Additionally, IP6 significantly (p = 0.006) inhibited the secretion of matrix metalloproteinase (MMP)-9 as assessed by zymography. The results of this study show that IP6 inhibits the metastasis of human breast cancer cells in vitro through effects on cancer cell adhesion, migration and invasion.

  9. 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.

  10. Time-dependent risk of depression, anxiety, and stress-related disorders in patients with invasive and in situ breast cancer.

    Science.gov (United States)

    Yang, Haomin; Brand, Judith S; Fang, Fang; Chiesa, Flaminia; Johansson, Anna L V; Hall, Per; Czene, Kamila

    2017-02-15

    Despite concerns about the mental health of breast cancer patients, little is known regarding the temporal risk pattern and risk factors of common mental disorders among these patients. We estimated standardized incidence ratios (SIRs) of depression, anxiety and stress-related disorders in a Swedish nationwide cohort of 40,849 women with invasive and 4,402 women with in situ breast cancer (2001-2010, median follow-up = 4.5 years). The impact of patient, tumor and treatment characteristics was analyzed using flexible parametric survival models in a regional cohort of 7,940 invasive breast cancer patients (2001-2013, median follow-up = 7.5 years). Women with invasive breast cancer showed increased rates of depression, anxiety and stress-related disorders [overall SIR (95% CI) = 1.57 (1.46-1.69), 1.55 (1.43-1.68) and 1.77 (1.60-1.95), respectively]. SIRs were highest shortly after diagnosis, but remained increased up to 5 years. Younger age at diagnosis, comorbidity, higher-grade disease, lymph node involvement and chemotherapy were independently associated with the risk of depression and anxiety in invasive cancer patients, with chemotherapy and higher-grade disease conferring short-term risk only, while comorbidities were mainly associated with late-onset events. No clinical risk factors were identified for stress-related disorders except for a greater risk associated with younger age. Patients with in situ cancer only showed an increased incidence of stress-related disorders during the first 6 months after diagnosis [SIR (95% CI) = 2.76 (1.31-5.79)]. The time-dependent risk profile of invasive cancer patients may guide health care professionals for timely and targeted psycho-oncologic interventions. © 2016 UICC.

  11. 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.

  12. c-Myb regulates matrix metalloproteinases 1/9, and cathepsin D: implications for matrix-dependent breast cancer cell invasion and metastasis

    Directory of Open Access Journals (Sweden)

    Knopfová Lucia

    2012-03-01

    Full Text Available Abstract Background The c-Myb transcription factor is essential for the maintenance of stem-progenitor cells in bone marrow, colon epithelia, and neurogenic niches. c-Myb malfunction contributes to several types of malignancies including breast cancer. However, the function of c-Myb in the metastatic spread of breast tumors remains unexplored. In this study, we report a novel role of c-Myb in the control of specific proteases that regulate the matrix-dependent invasion of breast cancer cells. Results Ectopically expressed c-Myb enhanced migration and ability of human MDA-MB-231 and mouse 4T1 mammary cancer cells to invade Matrigel but not the collagen I matrix in vitro. c-Myb strongly increased the expression/activity of cathepsin D and matrix metalloproteinase (MMP 9 and significantly downregulated MMP1. The gene coding for cathepsin D was suggested as the c-Myb-responsive gene and downstream effector of the migration-promoting function of c-Myb. Finally, we demonstrated that c-Myb delayed the growth of mammary tumors in BALB/c mice and affected the metastatic potential of breast cancer cells in an organ-specific manner. Conclusions This study identified c-Myb as a matrix-dependent regulator of invasive behavior of breast cancer cells.

  13. c-Myb regulates matrix metalloproteinases 1/9, and cathepsin D: implications for matrix-dependent breast cancer cell invasion and metastasis

    Science.gov (United States)

    2012-01-01

    Background The c-Myb transcription factor is essential for the maintenance of stem-progenitor cells in bone marrow, colon epithelia, and neurogenic niches. c-Myb malfunction contributes to several types of malignancies including breast cancer. However, the function of c-Myb in the metastatic spread of breast tumors remains unexplored. In this study, we report a novel role of c-Myb in the control of specific proteases that regulate the matrix-dependent invasion of breast cancer cells. Results Ectopically expressed c-Myb enhanced migration and ability of human MDA-MB-231 and mouse 4T1 mammary cancer cells to invade Matrigel but not the collagen I matrix in vitro. c-Myb strongly increased the expression/activity of cathepsin D and matrix metalloproteinase (MMP) 9 and significantly downregulated MMP1. The gene coding for cathepsin D was suggested as the c-Myb-responsive gene and downstream effector of the migration-promoting function of c-Myb. Finally, we demonstrated that c-Myb delayed the growth of mammary tumors in BALB/c mice and affected the metastatic potential of breast cancer cells in an organ-specific manner. Conclusions This study identified c-Myb as a matrix-dependent regulator of invasive behavior of breast cancer cells. PMID:22439866

  14. Male Breast Cancer

    Science.gov (United States)

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

  15. Breast Cancer Trends

    Science.gov (United States)

    ... 2011 Funding: Increasing Awareness and Support Among Young Women with Breast Cancer Funding: Young Breast Cancer Survivors Funding: Breast Cancer Genomics Statistics Rates by Race and Ethnicity Rates by State ...

  16. Better postdiagnosis diet quality is associated with reduced risk of death among postmenopausal women with invasive breast cancer in the women's health initiative.

    Science.gov (United States)

    George, Stephanie M; Ballard-Barbash, Rachel; Shikany, James M; Caan, Bette J; Freudenheim, Jo L; Kroenke, Candyce H; Vitolins, Mara Z; Beresford, Shirley A; Neuhouser, Marian L

    2014-04-01

    Few studies have evaluated whether adherence to dietary recommendations is associated with mortality among cancer survivors. In breast cancer survivors, we examined how postdiagnosis Healthy Eating Index (HEI)-2005 scores were associated with all-cause and cause-specific mortality. Our prospective cohort study included 2,317 postmenopausal women, ages 50 to 79 years, in the Women's Health Initiative's Dietary Modification Trial (n = 1,205) and Observational Study (n = 1,112), who were diagnosed with invasive breast cancer and completed a food frequency questionnaire after being diagnosed. We followed women from this assessment forward. We used Cox proportional hazards models to estimate multivariate-adjusted HRs and 95% confidence intervals (CI) for death from any cause, breast cancer, and causes other than breast cancer, according to HEI-2005 quintiles. Over 9.6 years, 415 deaths occurred. After adjustment for key covariates, women consuming better quality diets had a 26% lower risk of death from any cause (HRQ4:Q1, 0.74; 95% CI, 0.55-0.99; Ptrend = 0.043) and a 42% lower risk of death from non-breast cancer causes (HRQ4:Q1, 0.58; 95% CI, 0.38-0.87; Ptrend = 0.011). HEI-2005 score was not associated with breast cancer death (HRQ4:Q1, 0.91; 95% CI, 0.60-1.40; Ptrend = 0.627). In analyses stratified by tumor estrogen receptor (ER) status, better diet quality was associated with a reduced risk of all-cause mortality among women with ER(+) tumors (n = 1,758; HRQ4:Q1, 0.55; 95% CI, 0.38-0.79; Ptrend = 0.0009). Better postdiagnosis diet quality was associated with reduced risk of death, particularly from non-breast cancer causes. Breast cancer survivors may experience improved survival by adhering to U.S. dietary guidelines.

  17. Codonolactone, a sesquiterpene lactone isolated from Chloranthus henryi Hemsl, inhibits breast cancer cell invasion, migration and metastasis by downregulating the transcriptional activity of Runx2.

    Science.gov (United States)

    Wang, Wei; Chen, Bin; Zou, Ruolan; Tu, Xiuying; Tan, Songlin; Lu, Hong; Liu, Zhaojie; Fu, Jianjiang

    2014-11-01

    Metastasis is the most insidious aspect of breast cancer, but effective strategies to control this malignant process are still lacking. In previous studies, we screened over 200 extracts from plants of genus Chloranthaceae by bioactivity-guided fractionation, and found that Codonolactone (CLT) exhibited potential antimetastatic properties in breast cancer cells. This sesquiterpene lactone was isolated from Chloranthus henryi Hemsl, and is also found in other medical herbs, such as Codonopsis pilosula, Atractylodes macrocephala Koidz and others. Here, we report that CLT inhibited the ability of invasion and migration in metastatic breast cancer cells. Furthermore, CLT exhibited significant suppression on formation of lung metastatic foci of breast cancer in vivo. We next investigated the mechanism of CLT-induced metastasis inhibitory effects in breast cancer cells. A significant inhibition on activity and expression of MMP-9 and MMP-13 was observed. Moreover, data from western blotting, Runx2 transcription factor assay and chromatin immunoprecipitation assay showed that binding ability of Runx2 to sequences of the mmp-13 promoter was inhibited by CLT. Collectively, these findings suggested that the antimetastatic properties of CLT in breast cancer were due to the inhibition of MMPs, which might be associated with a downregulation of Runx2 transcriptional activity.

  18. Breast Cancer Surgery

    Science.gov (United States)

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

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

    OpenAIRE

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

    2013-01-01

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

  20. Breast cancer in pregnancy.

    Science.gov (United States)

    Krishna, Iris; Lindsay, Michael

    2013-09-01

    Pregnancy-associated breast cancer is defined as breast cancer diagnosed during pregnancy or in the first postpartum year. Breast cancer is one of the more common malignancies to occur during pregnancy and, as more women delay childbearing, the incidence of breast cancer in pregnancy is expected to increase. This article provides an overview of diagnosis, staging, and treatment of pregnancy-associated breast cancer. Recommendations for management of breast cancer in pregnancy are discussed. Copyright © 2013 Elsevier Inc. All rights reserved.

  1. 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.

  2. 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

  3. Interleukin-19 in Breast Cancer

    Directory of Open Access Journals (Sweden)

    Ying-Yin Chen

    2013-01-01

    Full Text Available Inflammatory cytokines within the tumor microenvironment are linked to progression in breast cancer. Interleukin- (IL- 19, part of the IL-10 family, contributes to a range of diseases and disorders, such as asthma, endotoxic shock, uremia, psoriasis, and rheumatoid arthritis. IL-19 is expressed in several types of tumor cells, especially in squamous cell carcinoma of the skin, tongue, esophagus, and lung and invasive duct carcinoma of the breast. In breast cancer, IL-19 expression is correlated with increased mitotic figures, advanced tumor stage, higher metastasis, and poor survival. The mechanisms of IL-19 in breast cancer have recently been explored both in vitro and in vivo. IL-19 has an autocrine effect in breast cancer cells. It directly promotes proliferation and migration and indirectly provides a microenvironment for tumor progression, which suggests that IL-19 is a prognostic marker in breast cancer and that antagonizing IL-19 may have therapeutic potential.

  4. The role of p53-microRNA 200-Moesin axis in invasion and drug resistance of breast cancer cells.

    Science.gov (United States)

    Alam, Farheen; Mezhal, Fatima; El Hasasna, Hussain; Nair, Vidhya A; Aravind, S R; Saber Ayad, Maha; El-Serafi, Ahmed; Abdel-Rahman, Wael M

    2017-09-01

    This study aimed to analyze the expression of microRNAs in relation to p53 status in breast cancer cells and to delineate the role of Moesin in this axis. We used three isogenic breast carcinoma cell lines MCF7 (with wild-type p53), 1001 (MCF7 with mutated p53), and MCF7-E6 (MCF7 in which p53 function was disrupted). MicroRNA expression was analyzed using microarray analysis and confirmed by real-time polymerase chain reaction. The 1001 clone with mutant p53 showed 22 upregulated and 25 downregulated microRNAs. The predicted targets of these 47 microRNAs were >700 human genes belonging to interesting functional groups such as stem cell development and maintenance. The most significantly downregulated microRNAs in the p53-mutant cell line were from the miR-200 family. We focused on miR-200c which targets many transcripts involved in epithelial-to-mesenchymal transition including Moesin. We found that Moesin was expressed in 1001 but not in its p53 wild-type parental MCF7 consistent with the observed mesenchymal features in the 1001, such as vimentin positivity, E-cadherin negativity, and ZEB1 positivity in addition to the morphological changes. After Moesin silencing, the p53-mutant cells 1001 reverted from mesenchymal-to-epithelial phenotype and showed subtle reduction in migration and invasion and loss of ZEB1 and SNAIL expression. Interestingly, Moesin silencing restored the 1001 sensitivity to Doxorubicin. These results indicate that loss of miR-200c, as a consequence of p53 mutation, can upregulate Moesin oncogene and thus promote carcinogenesis. Moesin may play a role in metastasis and drug resistance of breast cancer.

  5. Morin, a flavonoid from Moraceae, suppresses growth and invasion of the highly metastatic breast cancer cell line MDA-MB‑231 partly through suppression of the Akt pathway.

    Science.gov (United States)

    Jin, Hana; Lee, Won Sup; Eun, So Young; Jung, Ji Hyun; Park, Hyeon-Soo; Kim, Gonsup; Choi, Yung Hyun; Ryu, Chung Ho; Jung, Jin Myung; Hong, Soon Chan; Shin, Sung Chul; Kim, Hye Jung

    2014-10-01

    Morin, a flavonoid found in figs and other Moraceae, displays a variety of biological actions, such as anti-oxidant, anti-inflammatory and anti-carcinogenic. However, the anticancer effects of morin and in particular its anti-metastatic effects are not well known. Therefore, in the present study, we investigated the anticancer effects of morin on highly metastatic human breast cancer cells. Our results showed that morin significantly inhibited the colony forming ability of highly metastatic MDA-MB‑231 breast cancer cells from low doses (50 µM) without cytotoxicity. In addition, morin changed MDA-MB‑231 cell morphology from mesenchymal shape to epithelial shape and inhibited the invasion of MDA-MB‑231 cells in a dose-dependent manner. Morin decreased matrix metalloproteinase-9 (MMP-9) secretion and expression of the mesenchymal marker N-cadherin of MDA-MB‑231 cells, suggesting that morin might suppress the EMT process. Furthermore, morin significantly decreased the phosphorylation of Akt, and inhibition of the Akt pathway significantly reduced MDA-MB‑231 invasion. In an in vivo xenograft mouse model, morin suppressed MDA-MB‑231 cancer cell progression. Taken together, our findings suggest that morin exhibits an inhibitory effect on the cancer progression and EMT process of highly metastatic breast cancer cells at least in part through inhibiting Akt activation. This study provides evidence that morin may have anticancer effects against metastatic breast cancer.

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

    Science.gov (United States)

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

    2016-05-05

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

  7. Impaired MicroRNA Processing Facilitates Breast Cancer Cell Invasion by Upregulating Urokinase-Type Plasminogen Activator Expression

    National Research Council Canada - National Science Library

    Noh, Hyangsoon; Hong, Sungguan; Dong, Zheng; Pan, Zhixing K; Jing, Qing; Huang, Shuang

    2011-01-01

    ...) expression in breast cancer cells. Short hairpin RNAs specific for Drosha, DGCR8, and Dicer, key components of miRNA processing machinery, were introduced into 2 breast cancer cell lines with high uPA expression and 2 lines with poor uPA expression...

  8. Analysis of factors influencing the degree of detectability on diffusion-weighted MRI and diffusion background signals in patients with invasive breast cancer.

    Science.gov (United States)

    Hahn, Soo Yeon; Ko, Eun Sook; Han, Boo-Kyung; Lim, Yaeji; Gu, Seonhye; Ko, Eun Young

    2016-07-01

    To determine the factors influencing the degree of detectability of lesions and diffusion background signals on magnetic resonance diffusion-weighted imaging (DWI) in invasive breast cancer.Institutional review board approval was obtained and patient consent was waived. Patients with newly diagnosed invasive ductal carcinoma, who underwent preoperative breast magnetic resonance imaging with DWI were included in this study (n = 167). Lesion detectability on DWI and contrast-enhanced subtracted T1-weighted images, the degree of background parenchymal enhancement (BPE), and diffusion background signal were qualitatively rated. Detectability of lesions on DWI was compared with clinicopathological findings including menopausal status, mammographic density, and molecular subtype of breast cancer. Multivariate linear regression analysis was performed to determine variables independently associated with detectability of lesions on DWI and diffusion background signals.Univariate analysis showed that the detectability of lesions on DWI was significantly associated with lesion size (P = 0.001), diffuse background signal (P enhanced T1-weighted subtraction images (P = 0.000). The degree of diffusion background signal was significantly affected by age (P breast cancer. Only BPE was correlated with the amount of diffusion background signal on DWI (P breast cancers, detectability on DWI was significantly affected by the diffusion background signal. BPE, menopausal status, menstrual cycle, or mammographic density did not show statistically significant correlation with the diffusion detectability of lesions on DWI.

  9. 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.

  10. 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

  11. Gain of oncogenic function of p53 mutants induces invasive phenotypes in human breast cancer cells by silencing CCN5/WISP-2.

    Science.gov (United States)

    Dhar, Gopal; Banerjee, Snigdha; Dhar, Kakali; Tawfik, Ossama; Mayo, Matthew S; Vanveldhuizen, Peter J; Banerjee, Sushanta K

    2008-06-15

    CCN5/WISP-2 is overexpressed in noninvasive breast cancer cells and tissue samples, whereas its expression is minimal or undetected in invasive conditions. CCN5/WISP-2 has been considered as an antiinvasive gene because CCN5/WISP-2 silencing augments the invasive phenotypes in vitro. However, the mechanism of silencing of CCN5 during the progression of the disease has been elusive. Because p53 mutations are associated with breast cancer progression and have been shown to correlate inversely with CCN5/WISP-2 expression in other cancer cell types, the objective of this study was to explore whether p53 mutants suppress CCN5 expression in breast tumor cells resulting in the progression of this disease. We found CCN5 expression is inversely correlated with the mutational activation of p53 in human breast tumor cells. The ectopic expression of p53 mutants in ER-positive noninvasive breast tumor cells silenced the CCN5/WISP-2 expression and enhanced invasive phenotypes, including the induction of morphologic changes from the epithelial-to-mesenchymal type along with the alterations of hallmark proteins of these cell types and an augmentation of the migration of these cells. The suppression of CCN5 by the p53 mutants can be nullified by estrogen signaling in these cells through the transcriptional activation of the CCN5 gene. Moreover, the invasive changes can be imitated by blocking the CCN5/WISP-2 expression through RNA interference or can be reversed by the addition of CCN5/WISP-2 recombinant protein in the culture. Thus, these studies suggest that CCN5 inactivation could be an essential molecular event for p53 mutant-induced invasive phenotypes.

  12. Treatment Option Overview (Breast Cancer)

    Science.gov (United States)

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

  13. General Information about Breast Cancer

    Science.gov (United States)

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

  14. Murine model of hepatic breast cancer.

    Science.gov (United States)

    Rikhi, Rishi; Wilson, Elizabeth M; Deas, Olivier; Svalina, Matthew N; Bial, John; Mansoor, Atiya; Cairo, Stefano; Keller, Charles

    2016-12-01

    Breast cancer is the most common cancer in women and the second leading cause of cancer-related deaths in this population. Breast cancer related deaths have declined due to screening and adjuvant therapies, yet a driving clinical need exists to better understand the cause of the deadliest aspect of breast cancer, metastatic disease. Breast cancer metastasizes to several distant organs, the liver being the third most common site. To date, very few murine models of hepatic breast cancer exist. In this study, a novel murine model of liver breast cancer using the MDA-MB-231 cell line is introduced as an experimental (preclinical) model. Histological typing revealed consistent hepatic breast cancer tumor foci. Common features of the murine model were vascular invasion, lung metastasis and peritoneal seeding. The novel murine model of hepatic breast cancer established in this study provides a tool to be used to investigate mechanisms of hepatic metastasis and to test potential therapeutic interventions.

  15. Platinum Based Chemotherapy or Capecitabine in Treating Patients With Residual Triple-Negative Basal-Like Breast Cancer Following Neoadjuvant Chemotherapy

    Science.gov (United States)

    2017-10-03

    Estrogen Receptor Negative; HER2/Neu Negative; Invasive Breast Carcinoma; Progesterone Receptor Negative; Stage II Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage III Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Triple-Negative Breast Carcinoma

  16. Trends in invasive breast cancer incidence among French women not exposed to organized mammography screening: an age-period-cohort analysis.

    Science.gov (United States)

    Viel, Jean-François; Rymzhanova, Raouchan; Fournier, Evelyne; Danzon, Arlette

    2011-12-01

    The long tenure of the Doubs cancer registry (France) and the late implementation of a mass screening program provide a unique opportunity to assess the relative contributions of age, period and cohort effects to the increase in female invasive breast cancer incidence, while avoiding the influence of an organized screening program. Population and incidence data were provided for the Doubs region during the 1978-2003 period. Breast cancer counts and person-years were tabulated into 1-year classes by age and time period. Age-period-cohort models with parametric smooth functions were fitted to the data, assuming a Poisson distribution for the number of observed cases. A total of 5688 incident cases of invasive breast cancer in women were diagnosed in women aged 30-84 years in the Doubs region between 1978 and 2003. The annual percentage increase in incidence is 2.09%. Age effects rise dramatically until age 50, and at a slower pace afterwards. Large cohort curvature effects (pDoubs region. Although the future trend for breast cancer incidence is difficult to predict, the introduction of an organized screening program, and the sharp decline in hormone replacement therapy use will likely contribute to period effects in future analyses. Copyright © 2011 Elsevier Ltd. All rights reserved.

  17. Lattice-based model of ductal carcinoma in situ suggests rules for breast cancer progression to an invasive state.

    Directory of Open Access Journals (Sweden)

    Eline Boghaert

    2014-12-01

    Full Text Available Ductal carcinoma in situ (DCIS is a heterogeneous group of non-invasive lesions of the breast that result from abnormal proliferation of mammary epithelial cells. Pathologists characterize DCIS by four tissue morphologies (micropapillary, cribriform, solid, and comedo, but the underlying mechanisms that distinguish the development and progression of these morphologies are not well understood. Here we explored the conditions leading to the emergence of the different morphologies of DCIS using a two-dimensional multi-cell lattice-based model that incorporates cell proliferation, apoptosis, necrosis, adhesion, and contractility. We found that the relative rates of cell proliferation and apoptosis governed which of the four morphologies emerged. High proliferation and low apoptosis favored the emergence of solid and comedo morphologies. In contrast, low proliferation and high apoptosis led to the micropapillary morphology, whereas high proliferation and high apoptosis led to the cribriform morphology. The natural progression between morphologies cannot be investigated in vivo since lesions are usually surgically removed upon detection; however, our model suggests probable transitions between these morphologies during breast cancer progression. Importantly, cribriform and comedo appear to be the ultimate morphologies of DCIS. Motivated by previous experimental studies demonstrating that tumor cells behave differently depending on where they are located within the mammary duct in vivo or in engineered tissues, we examined the effects of tissue geometry on the progression of DCIS. In agreement with our previous experimental work, we found that cells are more likely to invade from the end of ducts and that this preferential invasion is regulated by cell adhesion and contractility. This model provides additional insight into tumor cell behavior and allows the exploration of phenotypic transitions not easily monitored in vivo.

  18. 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.

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

    DEFF Research Database (Denmark)

    Kim, Jiyoung; Villadsen, René; Sørlie, Therese

    2012-01-01

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

  20. [Prognostic differences of phenotypes in pT1-2N0 invasive breast cancer: a large cohort study with cluster analysis].

    Science.gov (United States)

    Wang, Z; Wang, W H; Wang, S L; Jin, J; Song, Y W; Liu, Y P; Ren, H; Fang, H; Tang, Y; Chen, B; Qi, S N; Lu, N N; Li, N; Tang, Y; Liu, X F; Yu, Z H; Li, Y X

    2016-06-23

    To find phenotypic subgroups of patients with pT1-2N0 invasive breast cancer by means of cluster analysis and estimate the prognosis and clinicopathological features of these subgroups. From 1999 to 2013, 4979 patients with pT1-2N0 invasive breast cancer were recruited for hierarchical clustering analysis. Age (≤40, 41-70, 70+ years), size of primary tumor, pathological type, grade of differentiation, microvascular invasion, estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER-2) were chosen as distance metric between patients. Hierarchical cluster analysis was performed using Ward's method. Cophenetic correlation coefficient (CPCC) and Spearman correlation coefficient were used to validate clustering structures. The CPCC was 0.603. The Spearman correlation coefficient was 0.617 (P40 years, smaller primary tumor, lower histologic grade, positive ER and PR status, and mainly negative HER-2. Patients in the cluster 1 and 11 had the worst prognosis, The cluster 1 was characterized by a larger tumor, higher grade and negative ER and PR status, while the cluster 11 was characterized by positive microvascular invasion. Patients in other 7 clusters had a moderate prognosis, and patients in each cluster had distinctive clinicopathological features and recurrent patterns. This study identified distinctive clinicopathologic phenotypes in a large cohort of patients with pT1-2N0 breast cancer through hierarchical clustering and revealed different prognosis. This integrative model may help physicians to make more personalized decisions regarding adjuvant therapy.

  1. High levels of γ-glutamyl hydrolase (GGH are associated with poor prognosis and unfavorable clinical outcomes in invasive breast cancer

    Directory of Open Access Journals (Sweden)

    Shubbar Emman

    2013-02-01

    Full Text Available Abstract Background Previously, we performed analysis of gene expression in 46 axillary lymph node negative tumors and identified molecular gene signatures that resulted in different clinical outcomes. The aim of this study was to determine the correlation of γ-glutamyl hydrolase (GGH, fatty acid amide hydrolase (FAAH, Pirin (PIR and TAF5-like RNA polymerase II, p300/CBP-associated factor (PCAF-associated factor, 65 kDa (TAF5L, selected from identified gene signatures, with clinical outcomes as well as classical clinicopathological characteristics in primary invasive breast cancer patients. Methods The protein levels of GGH, FAAH, PIR and TAF5L were assessed by immunohistochemistry (IHC on a panel of 80 primary invasive breast tumors. Quantitative real-time PCR (qRT-PCR and western blot analysis were performed to verify the expression levels of the candidate biomarkers. Patient disease-specific survival (DSS and recurrence-free survival (RFS were evaluated using the Kaplan-Meier method. The prognostic biomarkers were identified by univariate analysis with a log-rank test and by multivariate analysis with Cox proportional hazards regression models. Results The GGH and FAAH protein levels were significantly up-regulated in invasive breast cancer tumors compared with adjacent non-cancerous tissues. Furthermore, the protein levels of GGH and FAAH were significantly correlated in tumor tissues. Tumoral GGH protein expression was significantly correlated with shorter DSS and RFS. Furthermore, the protein expression of GGH was positively correlated with undifferentiated tumors (BRE grade III and ER/PR expressing tumors. Multivariate regression analysis showed that only GGH protein expression independently predicts DSS. No such correlations were found for FAAH, PIR and TAF5L protein expression. However, elevated protein levels of FAAH were positively associated with high number of lymph node involvement and upregulated levels of PIR were positively

  2. Breast Cancer Disparities

    Science.gov (United States)

    ... 2.65 MB] Read the MMWR Science Clips Breast Cancer Black Women Have Higher Death Rates from Breast ... of Page U.S. State Info Number of Additional Breast Cancer Deaths Among Black Women, By State SOURCE: National ...

  3. 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.

    Science.gov (United States)

    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 cancer. Reproductive history (age at first full-term pregnancy and parity), exposure to endogenous and exogenous hormones, height, and health behaviors were accounted for in the analyses. Relative indices of inequality (RII) for education were estimated using Cox regression models. A higher risk of invasive breast cancer was found among women with higher levels of education (RII = 1.22, 95% confidence interval (CI): 1.09, 1.37). This association was not observed among nulliparous women (RII = 1.13, 95% CI: 0.84, 1.52). Inequalities in breast cancer incidence decreased substantially after adjusting for reproductive history (RII = 1.11, 95% CI: 0.98, 1.25), with most of the association being explained by age at first full-term pregnancy. Each other risk factor explained a small additional part of the inequalities in breast cancer incidence. Height accounted for most of the remaining differences in incidence. After adjusting for all known risk factors, the authors found no association between education level and risk of invasive breast cancer. Inequalities in incidence were more pronounced for in situ breast cancer, and those inequalities remained after adjustment for all known risk factors (RII = 1.61, 95% CI: 1.07, 2.41), especially among nulliparous women.

  4. 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.

  5. Identification of TG100-115 as a new and potent TRPM7 kinase inhibitor, which suppresses breast cancer cell migration and invasion.

    Science.gov (United States)

    Song, Chiman; Bae, Yeonju; Jun, JinJoo; Lee, Hyomin; Kim, Nam Doo; Lee, Kyung-Bok; Hur, Wooyoung; Park, Jae-Yong; Sim, Taebo

    2017-04-01

    Transient receptor potential melastatin 7 (TRPM7) regulates breast cancer cell proliferation, migration, invasion and metastasis in its ion channel- and kinase domain-dependent manner. The pharmacological effects of TRPM7 ion channel inhibitors on breast cancer cells have been studied, but little is known about the effects of TRPM7 kinase domain inhibitors due to lack of potent TRPM7 kinase inhibitors. Screening was performed by using TRPM7 kinase assay. Effects of TG100-115 on breast cancer cell proliferation, migration, invasion, myosin IIA phosphorylation, and TRPM7 ion channel activity were assessed by using MTT, wound healing, transwell assay, Western blotting, and patch clamping, respectively. We found that CREB peptide is a potent substrate for the TR-FRET based TRPM7 kinase assay. Using this method, we discovered a new and potent TRPM7 kinase inhibitor, TG100-115. TG100-115 inhibited TRPM7 kinase activity in an ATP competitive fashion with over 70-fold stronger activity than that of rottlerin, known as a TRPM7 kinase inhibitor. TG100-115 has little effect on proliferation of MDA-MB-231 cells, but significantly decreases cell migration and invasion. Moreover, TG100-115 inhibits TRPM7 kinase regulated phosphorylation of the myosin IIA heavy chain and phosphorylation of focal adhesion kinase. TG100-115 also suppressed TRPM7 ion channel activity. TG100-115 can be used as a potent TRPM7 kinase inhibitor and a potent inhibitor of breast cancer cell migration. TG100-115 could be a useful tool for studying the pharmacological effects of TRPM7 kinase activity aimed at providing insight into new therapeutic approaches to the treatment of breast cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Dioxin emissions from a municipal solid waste incinerator and risk of invasive breast cancer: a population-based case-control study with GIS-derived exposure

    Directory of Open Access Journals (Sweden)

    Challier Bruno

    2008-01-01

    Full Text Available Abstract Background To date, few epidemiologic studies have examined the relationship between environmental PCDD/F exposure and breast cancer in human populations. Dioxin emissions from municipal solid waste incinerators (MSWIs are one of the major sources of environmental dioxins and are therefore an exposure source of public concern. The purpose of this study was to examine the association between dioxins emitted from a polluting MSWI and invasive breast cancer risk among women residing in the area under direct influence of the facility. Methods We compared 434 incident cases of invasive breast cancer diagnosed between 1996 and 2002, and 2170 controls randomly selected from the 1999 population census. A validated dispersion model was used as a proxy for dioxin exposure, yielding four exposure categories. The latter were linked to individual places of residence, using Geographic Information System technology. Results The age distribution at diagnosis for all cases combined showed a bimodal pattern with incidence peaks near 50 and 70 years old. This prompted us to run models separately for women aged 20–59 years, and women aged 60 years or older. Among women younger than 60 years old, no increased or decreased risk was found for any dioxin exposure category. Conversely, women over 60 years old living in the highest exposed zone were 0.31 time less likely (95% confidence interval, 0.08–0.89 to develop invasive breast cancer. Conclusion Before speculating that this decreased risk reflects a dioxin anti-estrogenic activity with greater effect on late-onset acquired breast cancer, some residual confounding must be envisaged.

  7. Dioxin emissions from a municipal solid waste incinerator and risk of invasive breast cancer: a population-based case-control study with GIS-derived exposure.

    Science.gov (United States)

    Viel, Jean-François; Clément, Marie-Caroline; Hägi, Mathieu; Grandjean, Sébastien; Challier, Bruno; Danzon, Arlette

    2008-01-28

    To date, few epidemiologic studies have examined the relationship between environmental PCDD/F exposure and breast cancer in human populations. Dioxin emissions from municipal solid waste incinerators (MSWIs) are one of the major sources of environmental dioxins and are therefore an exposure source of public concern. The purpose of this study was to examine the association between dioxins emitted from a polluting MSWI and invasive breast cancer risk among women residing in the area under direct influence of the facility. We compared 434 incident cases of invasive breast cancer diagnosed between 1996 and 2002, and 2170 controls randomly selected from the 1999 population census. A validated dispersion model was used as a proxy for dioxin exposure, yielding four exposure categories. The latter were linked to individual places of residence, using Geographic Information System technology. The age distribution at diagnosis for all cases combined showed a bimodal pattern with incidence peaks near 50 and 70 years old. This prompted us to run models separately for women aged 20-59 years, and women aged 60 years or older. Among women younger than 60 years old, no increased or decreased risk was found for any dioxin exposure category. Conversely, women over 60 years old living in the highest exposed zone were 0.31 time less likely (95% confidence interval, 0.08-0.89) to develop invasive breast cancer. Before speculating that this decreased risk reflects a dioxin anti-estrogenic activity with greater effect on late-onset acquired breast cancer, some residual confounding must be envisaged.

  8. Shear-wave elastography and immunohistochemical profiles in invasive breast cancer: evaluation of maximum and mean elasticity values.

    Science.gov (United States)

    Ganau, Sergi; Andreu, Francisco Javier; Escribano, Fernanda; Martín, Amaya; Tortajada, Lidia; Villajos, Maite; Baré, Marisa; Teixidó, Milagros; Ribé, Judit; Sentís, Melcior

    2015-04-01

    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. 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. 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). We were unable to demonstrate statistically significant differences among the subtypes of invasive tumors, although there appears to be a trend toward lower Emax and Emean in the aggressive phenotypes. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  9. Breast cancer in men

    Science.gov (United States)

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

  10. Saussurea lappa Clarke-Derived Costunolide Prevents TNFα-Induced Breast Cancer Cell Migration and Invasion by Inhibiting NF-κB Activity

    Directory of Open Access Journals (Sweden)

    Youn Kyung Choi

    2013-01-01

    Full Text Available Saussurea lappa Clarke (SLC has been used as a traditional medicine in Korea, China, and Japan for the treatment of abdominal pain and tenesmus. Costunolide, a sesquiterpene lactone isolated from SLC, has diverse medicinal effects. However, the anticancer effects of costunolide are still unclear in breast cancer. In this study, we demonstrate that costunolide suppresses tumor growth and metastases of MDA-MB-231 highly metastatic human breast cancer cells via inhibiting TNFα-induced NF-κB activation. Costunolide inhibited MDA-MB-231 tumor growth and metastases without affecting body weights in the in vivo mouse orthotopic tumor growth assays. In addition, costunolide inhibited in vitro TNFα-induced invasion and migration of MDA-MB-231 cells. Costunolide further suppressed TNFα-induced NF-κB signaling activation, resulting in a reduced expression of MMP-9, a well-known NF-κB-dependent gene to mediate breast cancer cell growth and metastases. Therefore, we conclude that SLC and its derivative costunolide suppress breast cancer growth and metastases by inhibiting TNFα-induced NF-κB activation, suggesting that costunolide as well as SLC may be promising anticancer drugs, especially for metastatic breast cancer.

  11. Cotylenin A and arsenic trioxide cooperatively suppress cell proliferation and cell invasion activity in human breast cancer cells.

    Science.gov (United States)

    Kasukabe, Takashi; Okabe-Kado, Junko; Kato, Nobuo; Honma, Yoshio; Kumakura, Shunichi

    2015-02-01

    Arsenic trioxide (ATO) is an approved treatment for acute promyelocytic leukemia (APL). It has also shown potential for treatment of multiple myeloma and various solid tumors including breast cancer. The requirement of high, toxic concentrations for the induction of apoptosis in non-APL and solid tumor cells is a major limitation for its use in other hematological malignancies and solid tumors. We have examined whether inducers of differentiation of leukemia cells can control the growth of solid tumor cells. In the present study, we found that cotylenin A, a plant growth regulator and a potent inducer of differentiation in myeloid leukemia cells, significantly potentiated both ATO-induced inhibition of cell growth in a liquid culture, and ATO-induced inhibition of anchorage-independent growth in a semi-solid culture in human breast cancer MCF-7 and MDA-MB-231 cells. ISIR-005 (a synthetic cotylenin A-derivative) was also able to enhance ATO-induced growth inhibition. The combined treatment with cotylenin A and ATO induced cleaved caspase-7 in MCF-7 cells at the concentrations which ATO alone scarcely induced and cotylenin A alone only weakly induced. Expression of survivin in MCF-7 cells was markedly decreased with the presence of both cotylenin A and ATO, although the expression of survivin was only slightly decreased by cotylenin A or ATO alone. The pretreatment with N-acetylcysteine significantly reduced the combination treatment-induced cell growth inhibition. These data suggest that induction of cleaved caspase-7, inhibition of survivin and oxidative responses are important events in the corporative inhibition in the growth of MCF-7 cells induced by both cotylenin A and ATO. Furthermore, we found that the combined treatment with cotylenin A and ATO also could be effective in suppressing the invasive capacity of MDA-MB-231 cells determined with the impedance-based xCELLigence Real-Time Cell Analysis technology. These results suggest that cotylenin A is an

  12. Optimizing non-invasive radiofrequency hyperthermia treatment for improving drug delivery in 4T1 mouse breast cancer model.

    Science.gov (United States)

    Ware, Matthew J; Krzykawska-Serda, Martyna; Chak-Shing Ho, Jason; Newton, Jared; Suki, Sarah; Law, Justin; Nguyen, Lam; Keshishian, Vazrik; Serda, Maciej; Taylor, Kimberly; Curley, Steven A; Corr, Stuart J

    2017-03-13

    Interactions of high-frequency radio waves (RF) with biological tissues are currently being investigated as a therapeutic platform for non-invasive cancer hyperthermia therapy. RF delivers thermal energy into tissues, which increases intra-tumoral drug perfusion and blood-flow. Herein, we describe an optical-based method to optimize the short-term treatment schedules of drug and hyperthermia administration in a 4T1 breast cancer model via RF, with the aim of maximizing drug localization and homogenous distribution within the tumor microenvironment. This method, based on the analysis of fluorescent dyes localized into the tumor, is more time, cost and resource efficient, when compared to current analytical methods for tumor-targeting drug analysis such as HPLC and LC-MS. Alexa-Albumin 647 nm fluorphore was chosen as a surrogate for nab-paclitaxel based on its similar molecular weight and albumin driven pharmacokinetics. We found that RF hyperthermia induced a 30-40% increase in Alexa-Albumin into the tumor micro-environment 24 h after treatment when compared to non-heat treated mice. Additionally, we showed that the RF method of delivering hyperthermia to tumors was more localized and uniform across the tumor mass when compared to other methods of heating. Lastly, we provided insight into some of the factors that influence the delivery of RF hyperthermia to tumors.

  13. Optimizing non-invasive radiofrequency hyperthermia treatment for improving drug delivery in 4T1 mouse breast cancer model

    Science.gov (United States)

    Ware, Matthew J.; Krzykawska-Serda, Martyna; Chak-Shing Ho, Jason; Newton, Jared; Suki, Sarah; Law, Justin; Nguyen, Lam; Keshishian, Vazrik; Serda, Maciej; Taylor, Kimberly; Curley, Steven A.; Corr, Stuart J.

    2017-03-01

    Interactions of high-frequency radio waves (RF) with biological tissues are currently being investigated as a therapeutic platform for non-invasive cancer hyperthermia therapy. RF delivers thermal energy into tissues, which increases intra-tumoral drug perfusion and blood-flow. Herein, we describe an optical-based method to optimize the short-term treatment schedules of drug and hyperthermia administration in a 4T1 breast cancer model via RF, with the aim of maximizing drug localization and homogenous distribution within the tumor microenvironment. This method, based on the analysis of fluorescent dyes localized into the tumor, is more time, cost and resource efficient, when compared to current analytical methods for tumor-targeting drug analysis such as HPLC and LC-MS. Alexa-Albumin 647 nm fluorphore was chosen as a surrogate for nab-paclitaxel based on its similar molecular weight and albumin driven pharmacokinetics. We found that RF hyperthermia induced a 30-40% increase in Alexa-Albumin into the tumor micro-environment 24 h after treatment when compared to non-heat treated mice. Additionally, we showed that the RF method of delivering hyperthermia to tumors was more localized and uniform across the tumor mass when compared to other methods of heating. Lastly, we provided insight into some of the factors that influence the delivery of RF hyperthermia to tumors.

  14. Therapeutic IMC-C225 antibody inhibits breast cancer cell invasiveness via Vav2-dependent activation of RhoA GTPase.

    Science.gov (United States)

    Molli, Poonam R; Adam, Liana; Kumar, Rakesh

    2008-10-01

    Abnormalities in the expression and signaling pathways downstream of epidermal growth factor receptor (EGFR) contribute to progression, invasion, and maintenance of the malignant phenotype in human cancers. Accordingly, biological agents, such as the EGFR-blocking antibody IMC-C225 have promising anticancer potential and are currently in various stages of clinical development. Because use of IMC-C225 is limited, at present, only for treatment of cancer with high EGFR expression, the goal of the present study was to determine the effect of IMC-C225 on the invasiveness of breast cancer cells with high and low levels of EGFR expression. The effect of IMC-C225 on invasion was studied using breast cancer cell lines with high and low levels of EGFR expression. The addition of EGF led to progressive stress fiber dissolution. In contrast, cells treated with IMC-C225 showed reduced invasiveness and increased stress-fiber formation. Interestingly, IMC-C225 pretreatment was accompanied by EGFR phosphorylation, as detected using an anti-phosphorylated tyrosine antibody (PY99), which correlated with phosphorylation of Vav2 guanine nucleotide exchange factor and activation of RhoA GTPase irrespective of EGFR level, and Vav2 interacted with EGFR only in IMC-C225-treated cells. The underlying mechanism involved an enhanced interaction between beta1 integrins and EGFR upon IMC-C225 treatment. Here, we defined a new mechanism for IMC-C225 that cross-links integrins with EGFR, leading to activation of RhoA and inhibition of breast cancer cell invasion irrespective of the level of EGFR in the cells, thus providing a rationale for using IMC-C225 in the metastatic setting independent of the levels of EGFR.

  15. Downregulation of COX-2 and CYP 4A signaling by isoliquiritigenin inhibits human breast cancer metastasis through preventing anoikis resistance, migration and invasion

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, Hao; Li, Ying [Department of Pharmacology, School of Medicine, Wuhan University, Wuhan 430071 (China); Wang, Yuzhong [Key Laboratory for Oral Biomedical Engineering of Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan 430079 (China); Zhao, Haixia [Department of Pharmacology, School of Medicine, Wuhan University, Wuhan 430071 (China); Zhang, Jing [Animal Experimental Center of Wuhan University, Wuhan 430071 (China); Chai, Hongyan [Center for Gene Diagnosis, Zhongnan Hospital, Wuhan University, Wuhan 430071 (China); Tang, Tian [Department of Oncology, Renmin Hospital of Wuhan University, Wuhan 430060 (China); Yue, Jiang [Department of Pharmacology, School of Medicine, Wuhan University, Wuhan 430071 (China); Guo, Austin M., E-mail: Austin_Guo@nymc.edu [Department of Pharmacology, School of Medicine, Wuhan University, Wuhan 430071 (China); Department of Pharmacology, New York Medical College, Valhalla, NY 10595 (United States); Yang, Jing, E-mail: yangjingliu2013@163.com [Department of Pharmacology, School of Medicine, Wuhan University, Wuhan 430071 (China)

    2014-10-01

    Flavonoids exert extensive in vitro anti-invasive and in vivo anti-metastatic activities. Anoikis resistance occurs at multiple key stages of the metastatic cascade. Here, we demonstrate that isoliquiritigenin (ISL), a flavonoid from Glycyrrhiza glabra, inhibits human breast cancer metastasis by preventing anoikis resistance, migration and invasion through downregulating cyclooxygenase (COX)-2 and cytochrome P450 (CYP) 4A signaling. ISL induced anoikis in MDA-MB-231 and BT-549 human breast cancer cells as evidenced by flow cytometry and the detection of caspase cleavage. Moreover, ISL inhibited the mRNA expression of phospholipase A2, COX-2 and CYP 4A and decreased the secretion of prostaglandin E{sub 2} (PGE{sub 2}) and 20-hydroxyeicosatetraenoic acid (20-HETE) in detached MDA-MB-231 cells. In addition, it decreased the levels of phospho-PI3K (Tyr{sup 458}), phospho-PDK (Ser{sup 241}) and phospho-Akt (Thr{sup 308}). Conversely, the exogenous addition of PGE{sub 2}, WIT003 (a 20-HETE analog) and an EP4 agonist (CAY10580) or overexpression of constitutively active Akt reversed ISL-induced anoikis. ISL exerted the in vitro anti-migratory and anti-invasive activities, whereas the addition of PGE{sub 2}, WIT003 and CAY10580 or overexpression of constitutively active Akt reversed the in vitro anti-migratory and anti-invasive activities of ISL in MDA-MB-231 cells. Notably, ISL inhibited the in vivo lung metastasis of MDA-MB-231 cells, together with decreased intratumoral levels of PGE{sub 2}, 20-HETE and phospho-Akt (Thr{sup 308}). In conclusion, ISL inhibits breast cancer metastasis by preventing anoikis resistance, migration and invasion via downregulating COX-2 and CYP 4A signaling. It suggests that ISL could be a promising multi-target agent for preventing breast cancer metastasis, and anoikis could represent a novel mechanism through which flavonoids may exert the anti-metastatic activities. - Highlights: • Isoliquiritigenin induces anoikis and suppresses

  16. 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.

  17. MR imaging features associated with distant metastasis-free survival of patients with invasive breast cancer: a case-control study.

    Science.gov (United States)

    Song, Sung Eun; Shin, Sung Ui; Moon, Hyeong-Gon; Ryu, Han Suk; Kim, Kwangsoo; Moon, Woo Kyung

    2017-04-01

    Preoperative breast magnetic resonance (MR) imaging features of primary breast cancers may have the potential to act as prognostic biomarkers by providing morphologic and kinetic features representing inter- or intra-tumor heterogeneity. Recent radiogenomic studies reveal that several radiologist-annotated image features are associated with genes or signal pathways involved in tumor progression, treatment resistance, and distant metastasis (DM). We investigate whether preoperative breast MR imaging features are associated with worse DM-free survival in patients with invasive breast cancer. Of the 3536 patients with primary breast cancers who underwent preoperative MR imaging between 2003 and 2009, 147 patients with DM were identified and one-to-one matched with control patients (n = 147) without DM according to clinical-pathologic variables. Three radiologists independently reviewed the MR images of 294 patients, and the association of DM-free survival with MR imaging and clinical-pathologic features was assessed using Cox proportional hazard models. Of MR imaging features, rim enhancement (hazard ratio [HR], 1.83 [95% confidence interval, CI 1.29, 2.51]; p = 0.001) and peritumoral edema (HR, 1.48 [95% CI 1.03, 2.11]; p = 0.032) were the significant features associated with worse DM-free survival. The significant MR imaging features, however, were different between breast cancer subtypes and stages. Preoperative breast MR imaging features of rim enhancement and peritumoral edema may be used as prognostic biomarkers that help predict DM risk in patients with breast cancer, thereby potentially enabling improved personalized treatment and monitoring strategies for individual patients.

  18. Atomic force microscope-based single cell force spectroscopy of breast cancer cell lines: an approach for evaluating cellular invasion.

    Science.gov (United States)

    Omidvar, Ramin; Tafazzoli-Shadpour, Mohammad; Shokrgozar, Mohammad Ali; Rostami, Mostafa

    2014-10-17

    The adhesiveness of cancerous cells to their neighboring cells significantly contributes to tumor progression and metastasis. The single-cell force spectroscopy (SCFS) approach was implemented to survey the cell-cell adhesion force between cancerous cells in three cancerous breast cell lines (MCF-7, T47D, and MDA-MB-231). The gene expression levels of two dominant cell adhesion markers (E-cadherin and N-cadherin) were quantified by real-time PCR. Additionally, the local stiffness of the cell bodies was measured by atomic force microscopy (AFM), and the actin cytoskeletal organization was examined by confocal microscopy. Results indicated that the adhesion force between cells was conversely correlated with their invasion potential. The highest adhesion force was observed in the MCF-7 cells. A reduction in cell-cell adhesion, which is required for the detachment of cells from the main tumor during metastasis, is partly due to the loss of E-cadherin expression and the enhanced expression of N-cadherins. The reduced adhesion was accompanied by the softening of cells, as described by the rearrangement of actin filaments through confocal microscopy observations. The softening of the cell body and the reduced cellular adhesiveness are two adaptive mechanisms through which malignant cells achieve the increased deformability, motility, and strong metastasis potential necessary for passage through endothelial junctions and positioning in host tissue. This study presented application of SCFS to survey cell phenotype transformation during cancer progression. The results can be implemented as a platform for further investigations that target the manipulation of cellular adhesiveness and stiffness as a therapeutic choice. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Inhibitory effect of miR-184 on the potential of proliferation and invasion in human glioma and breast cancer cells in vitro.

    Science.gov (United States)

    Feng, Ren; Dong, Lei

    2015-01-01

    MiR-184 was an important suppressor to tumor cells proliferation and invasion and some studies show that it was down-regulated in aggressive human tumor cells and a potential tumor therapy target through expression of miR-184 results in reduced tumor cell aggressiveness. In this study, miR-184 showed an inhibitive activity of glioma U87MG cell line and breast cancer MCF-7 cell line in proliferation and invasion by MTS and transwell assay. We found that the miR-184 also could arrest cell cycle and adhesion by up-regulating the expression of p53 and p21 and activity of caspase-3/8, suppressing the expression of SND1, MMP-2/9, CD44 and activity of AKT/NF-κB pathway. The results showed that miR-184 could be a potential target for glioma and breast cancer treatment.

  20. Muscadine grape skin extract can antagonize Snail-cathepsin L-mediated invasion, migration and osteoclastogenesis in prostate and breast cancer cells.

    Science.gov (United States)

    Burton, Liza J; Smith, Basil A; Smith, Bethany N; Loyd, Quentin; Nagappan, Peri; McKeithen, Danielle; Wilder, Catera L; Platt, Manu O; Hudson, Tamaro; Odero-Marah, Valerie A

    2015-09-01

    To develop new and effective chemopreventive agents against bone metastasis, we assessed the effects of muscadine grape skin extract (MSKE), whose main bioactive component is anthocyanin, on bone turnover, using prostate and breast cancer cell models overexpressing Snail transcription factor. MSKE has been shown previously to promote apoptosis in prostate cancer cells without affecting normal prostate epithelial cells. Snail is overexpressed in prostate and breast cancer, and is associated with increased invasion, migration and bone turnover/osteoclastogenesis. Cathepsin L (CatL) is a cysteine cathepsin protease that is overexpressed in cancer and involved in bone turnover. Snail overexpression in prostate (LNCaP, ARCaP-E) and breast (MCF-7) cancer cells led to increased CatL expression/activity and phosphorylated STAT-3 (pSTAT-3), compared to Neo vector controls, while the reverse was observed in C4-2 (the aggressive subline of LNCaP) cells with Snail knockdown. Moreover, CatL expression was higher in prostate and breast tumor tissue compared to normal tissue. MSKE decreased Snail and pSTAT3 expression, and abrogated Snail-mediated CatL activity, migration and invasion. Additionally, Snail overexpression promoted osteoclastogenesis, which was significantly inhibited by the MSKE as effectively as Z-FY-CHO, a CatL-specific inhibitor, or osteoprotegerin, a receptor activator of nuclear factor kappa B ligand (RANKL) antagonist. Overall, these novel findings suggest that Snail regulation of CatL may occur via STAT-3 signaling and can be antagonized by MSKE, leading to decreased cell invasion, migration and bone turnover. Therefore, inhibition using a natural product such as MSKE could potentially be a promising bioactive compound for bone metastatic cancer. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  1. Imaging male breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Doyle, S., E-mail: sdoyle2@nhs.net [Primrose Breast Care Unit, Derriford Hospital, Plymouth (United Kingdom); Steel, J.; Porter, G. [Primrose Breast Care Unit, Derriford Hospital, Plymouth (United Kingdom)

    2011-11-15

    Male breast cancer is rare, with some pathological and radiological differences from female breast cancer. There is less familiarity with the imaging appearances of male breast cancer, due to its rarity and the more variable use of preoperative imaging. This review will illustrate the commonest imaging appearances of male breast cancer, with emphasis on differences from female breast cancer and potential pitfalls in diagnosis, based on a 10 year experience in our institution.

  2. 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

    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...... of patients diagnosed with DCIS, making a precise localization of nonpalpable DCIS lesions even more important....

  3. Ultrasound-guided excision combined with intraoperative assessment of gross macroscopic margins decreases the rate of reoperations for non-palpable invasive breast cancer.

    Science.gov (United States)

    Ramos, Manuel; Díaz, Juan Carlos; Ramos, Teresa; Ruano, Ricardo; Aparicio, Martín; Sancho, Magdalena; González-Orús, José María

    2013-08-01

    The standard technique for intraoperative tumour localization of clinically occult tumours is wire-guided localization (WGL). This, however, this has several disadvantages. The aim of the present work is to report our single-centre experience with intraoperative ultrasound-guided (IOUS) excision, performed by surgeons, combined with intraoperative assessment of macroscopic pathologic and ultrasound margins in non-palpable invasive cancers indicated for conservative breast therapy. Two-hundred and twenty-five non-palpable invasive breast cancers were subjected to excision with IOUS. The lesion was located in the operating room with a high-frequency ultrasound probe (8-12 MHz), which was then used to guide surgical removal. The specimen margins were estimated by ultrasonography and macroscopic pathologic examination. The sensitivity of IOUS and effectiveness in the characterization of the specimen margins were evaluated, assessing the need for reoperation. Pathologic tumour size was 12.0 ± 6.7 mm and 13 lesions (6.4 %) were margins in the 4% of cases (9/225). In 5 cases remains of in situ or invasive carcinoma were found. In two cases, conservative surgery was converted to mastectomy. IOUS excision combined with the intraoperative assessment of the macroscopic margins of non-palpable breast cancers is a safe, useful, and efficient technique. We obtained an excellent characterization of tumour margins with moderate removal of breast tissue and consequently a lower number of reoperations were required and good cosmetic results were obtained. We believe that use of this technique in conservative breast cancer surgery should be recommended. Copyright © 2012 Elsevier Ltd. All rights reserved.

  4. 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.

  5. Imaging features of breast cancers on digital breast tomosynthesis according to molecular subtype: association with breast cancer detection.

    Science.gov (United States)

    Lee, Su Hyun; Chang, Jung Min; Shin, Sung Ui; Chu, A Jung; Yi, Ann; Cho, Nariya; Moon, Woo Kyung

    2017-12-01

    To evaluate imaging features of breast cancers on digital breast tomosynthesis (DBT) according to molecular subtype and to determine whether the molecular subtype affects breast cancer detection on DBT. This was an institutional review board--approved study with a waiver of informed consent. DBT findings of 288 invasive breast cancers were reviewed according to Breast Imaging Reporting and Data System lexicon. Detectability of breast cancer was quantified by the number of readers (0-3) who correctly detected the cancer in an independent blinded review. DBT features and the cancer detectability score according to molecular subtype were compared using Fisher's exact test and analysis of variance. Of 288 invasive cancers, 194 were hormone receptor (HR)-positive, 48 were human epidermal growth factor receptor 2 (HER2) positive and 46 were triple negative breast cancers. The most common DBT findings were irregular spiculated masses for HR-positive cancer, fine pleomorphic or linear branching calcifications for HER2 positive cancer and irregular masses with circumscribed margins for triple negative breast cancers (p Cancer detectability on DBT was not significantly different according to molecular subtype (p = 0.213) but rather affected by tumour size, breast density and presence of mass or calcifications. Breast cancers showed different imaging features according to molecular subtype; however, it did not affect the cancer detectability on DBT. Advances in knowledge: DBT showed characteristic imaging features of breast cancers according to molecular subtype. However, cancer detectability on DBT was not affected by molecular subtype of breast cancers.

  6. P-Rex1 Expression in Invasive Breast Cancer in relation to Receptor Status and Distant Metastatic Site

    Directory of Open Access Journals (Sweden)

    Jonathan D. Marotti

    2017-01-01

    Full Text Available Background. Phosphatidylinositol-3,4,5-trisphosphate-dependent Rac exchange factor 1 (P-Rex1 has been implicated in cancer growth, metastasis, and response to phosphatidylinositol 3-kinase (PI3K inhibitor therapy. The aim of this study was to determine whether P-Rex1 expression differs between primary and metastatic human breast tumors and between breast cancer subtypes. Design. P-Rex1 expression was measured in 133 specimens by immunohistochemistry: 40 and 42 primary breast tumors from patients who did versus did not develop metastasis, respectively, and 51 breast-derived tumors from metastatic sites (36 of which had matching primary tumors available for analysis. Results. Primary breast tumors showed significant differences in P-Rex1 expression based on receptor subtype. ER+ and HER2+ primary tumors showed higher P-Rex1 expression than primary triple-negative tumors. HER2+ metastases from all sites showed significantly higher P-Rex1 expression compared to other metastatic receptor subtypes. Solid organ (i.e., brain, lung, and liver metastases showed higher P-Rex1 expression compared to bone metastases. Conclusions. P-Rex1 expression is increased in ER+ and HER2+ breast cancers compared to triple-negative tumors. P-Rex1 may be differentially expressed in metastatic tumors based on site and receptor status. The role of P-Rex1 in the development of breast cancer metastases and as a predictive biomarker of therapeutic response warrants further investigation.

  7. Obesity and Survival Among Black Women and White Women 35 to 64 Years of Age at Diagnosis With Invasive Breast Cancer

    Science.gov (United States)

    Lu, Yani; Ma, Huiyan; Malone, Kathleen E.; Norman, Sandra A.; Sullivan-Halley, Jane; Strom, Brian L.; Marchbanks, Polly A.; Spirtas, Robert; Burkman, Ronald T.; Deapen, Dennis; Folger, Suzanne G.; Simon, Michael S.; Press, Michael F.; McDonald, Jill A.; Bernstein, Leslie

    2011-01-01

    Purpose To evaluate the effect of obesity on survival among black women and white women with invasive breast cancer and to determine whether obesity explains the poorer survival of black women relative to white women. Patients and Methods We observed 4,538 (1,604 black, 2,934 white) women who were 35 to 64 years of age when diagnosed with incident invasive breast cancer between 1994 and 1998. Multivariate Cox regression models were used to examine the effect of body mass index (BMI, in kilograms per square meter) 5 years before diagnosis on risk of death from any cause and from breast cancer. Results During a median of 8.6 years of follow-up, 1,053 women died (519 black, 534 white), 828 as a result of breast cancer (412 black, 416 white). Black women were more likely to die than white women (multivariate-adjusted relative risk [RR], 1.33; 95% CI, 1.16 to 1.53). Compared with women with BMI of 20 to 24.9 kg/m2, those who were obese (BMI ≥ 30 kg/m2) had a greater risk of all-cause mortality (RR, 1.23; 95% CI, 1.04 to 1.47) and breast cancer–specific mortality (RR, 1.20; 95% CI, 0.99 to 1.46). These associations were observed among white women (all-cause RR, 1.54; 95% CI, 1.21 to 1.96; breast cancer RR, 1.46; 95% CI, 1.11 to 1.92), but not among black women (all-cause RR, 1.03; 95% CI, 0.81 to 1.29; breast cancer RR, 1.02; 95% CI, 0.79 to 1.33). Conclusion Obesity may play an important role in mortality among white but not black patients with breast cancer. It is unlikely that differences in obesity distributions between black women and white women account for the poorer survival of black women. PMID:21788570

  8. 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

  9. lincRNA-RoR and miR-145 regulate invasion in triple-negative breast cancer via targeting ARF6.

    Science.gov (United States)

    Eades, Gabriel; Wolfson, Benjamin; Zhang, Yongshu; Li, Qinglin; Yao, Yuan; Zhou, Qun

    2015-02-01

    Triple-negative (ER(-), HER2(-), PR(-)) breast cancer (TNBC) is an aggressive disease with a poor prognosis with no available molecularly targeted therapy. Silencing of microRNA-145 (miR-145) may be a defining marker of TNBC based on molecular profiling and deep sequencing. Therefore, the molecular mechanism behind miR-145 downregulation in TNBC was examined. Overexpression of the long intergenic noncoding RNA regulator of reprogramming, lincRNA-RoR, functions as a competitive endogenous RNA sponge in TNBC. Interestingly, lincRNA-RoR is dramatically upregulated in TNBC and in metastatic disease and knockdown restores miR-145 expression. Previous reports suggest that miR-145 has growth-suppressive activity in some breast cancers; however, these data in TNBC indicate that miR-145 does not affect proliferation or apoptosis but instead, miR-145 regulates tumor cell invasion. Investigation of miR-145-regulated pathways involved in tumor invasion revealed a novel target, the small GTPase ADP-ribosylation factor 6 (Arf6). Subsequent analysis demonstrated that ARF6, a known regulator of breast tumor cell invasion, is dramatically upregulated in TNBC and in breast tumor metastasis. Mechanistically, ARF6 regulates E-cadherin localization and affects cell-cell adhesion. These results reveal a lincRNA-RoR/miR-145/ARF6 pathway that regulates invasion in TNBCs. The lincRNA-RoR/miR-145/ARF6 pathway is critical to TNBC metastasis and could serve as biomarkers or therapeutic targets for improving survival. ©2014 American Association for Cancer Research.

  10. The tumour border on contrast-enhanced spectral mammography and its relation to histological characteristics of invasive breast cancer

    Directory of Open Access Journals (Sweden)

    Aleksandra Ambicka

    2016-11-01

    Full Text Available Contrast-enhanced spectral mammography (CESM is one of the new diagnostic modalities implemented in clinical practice. In the case of these techniques, there are two major issues to be addressed: (1 their diagnostic usefulness, and (2 the relation between parameters assessed using these techniques and well-known diagnostic/prognostic/predictive markers (histological, clinical, and molecular. Therefore, we studied the relationship between the tumour margin assessed on CESM and (1 tumour borders defined on the basis of macroscopic and microscopic examination, (2 pT, (3 pN, and (4 tumour grade in a group of 82 breast cancer patients. Based on CESM, the tumour border was defined as sharp, indistinct or spiculated, whereas in the case of lesions showing weak or medium enhancement on CESM the borders were classified as unspecified. We found a statistically significant relationship between tumour margin on CESM and (1 macroscopic border (a spiculated margin on CESM was found only in carcinomas with an invasive border on histological examination; p = 0.004, (2 pT (p = 0.016, and (3 pN (nodal involvement was observed most frequently in carcinomas with a spiculated or indistinct margin on CESM; p = 0.045. Moreover, in cases with an undefined margin on CESM (cases showing weak or medium enhancement on CESM, both invasive and pushing borders were found on histological examination. The results of our preliminary study suggest that it is possible to assess macroscopic borders of examined lesions on the basis of CESM imaging. This might be useful in planning the extent of surgical excision. On the other hand, the assessment of the tumour margin on CESM might not be precise in cases showing weak enhancement.

  11. Linc-ROR induces epithelial-mesenchymal transition and contributes to drug resistance and invasion of breast cancer cells.

    Science.gov (United States)

    Chen, Yao-Min; Liu, Yu; Wei, Hai-Yan; Lv, Ke-Zhen; Fu, Peifen

    2016-08-01

    We aimed to investigate the role of large intergenic noncoding RNA regulator of reprogramming (linc-ROR) in the chemotherapy resistance of human breast cancer (BC) cells and its mechanism. A total of 142 patients diagnosed with BC in the First Affiliated Hospital, Zhejiang University between January 2012 and January 2014 were enrolled in our study. The BC tissues and the adjacent normal tissues (5 cm away from tumor tissue) of the enrolled patients were selected, and human BC cell lines (MCF10A, SK-BR-3, MCF-7, Bcap-37, MDA-MB-231, and T47D) were also selected. Quantitative real-time polymerase chain reaction (qRT-PCR), Western blot, 3-(4, 5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) assay, and Transwell were applied in our study. Expression level of linc-ROR messenger RNA (mRNA) in BC tissues was clearly higher than that in adjacent normal tissues, and significant difference was found between expression level of linc-ROR mRNA and lymph node metastasis (all P ROR was highly expressed in others BC cell lines compared with that in immortalized mammary epithelial cells (MECs) MCF10A (both P ROR cell presented decreased sensibility of 5-FU and paclitaxel with decreased E-cadherin expression, increased Vimentin, N-cadherin expression, and invasion ability (all P ROR is an important marker for multidrug resistance of BC, and its up-regulation is important for chemotherapy tolerance and invasion of BC.

  12. Stages of Male Breast Cancer

    Science.gov (United States)

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

  13. ATP‐P2Y2‐β‐catenin axis promotes cell invasion in breast cancer cells

    National Research Council Canada - National Science Library

    Zhang, Jiang‐Lan; Liu, Ying; Yang, Hui; Zhang, Hong‐Quan; Tian, Xin‐Xia; Fang, Wei‐Gang

    2017-01-01

    .... Our previous study demonstrated that ATP treatment in vitro could promote invasion in human prostate cancer cells via P2Y2, a preferred receptor for ATP, by enhancing EMT process. However, the pro...

  14. 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

    characteristics and therapy. All statistical tests were two-sided. RESULTS: Complete follow-up was achieved for 15,659 patients. The median estimated potential follow-up was 6.4 years for invasive disease-free interval and 7.7 years for overall survival. Invasive disease-free interval and overall survival were...... high-risk criterion. Lymphovascular invasion should not by itself be considered sufficient to move patients from a low-risk group to a high-risk group....

  15. "Smart" Nanoparticles Enhance the Cytoplasmic Delivery of Anti-RhoC Silencing RNA and Inhibit the Migration and Invasion of Aggressive Breast Cancer Cells.

    Science.gov (United States)

    Kaushal, Neha; Durmaz, Yasemin Yuksel; Bao, LeWei; Merajver, Sofia D; ElSayed, Mohamed E H

    2015-07-06

    Rho-GTPases are small GTP-binding proteins that contribute to the epithelial-to-mesenchymal transition by regulating several cellular processes including organization of the actin cytoskeleton, cell motility, transcription, and cell proliferation. Overexpression of RhoC-GTPases (RhoC) in breast cancer has been implicated in poor disease prognosis due to increased cancer cells invasion, migration, and motility, which warranted its consideration as a therapeutic target for inhibiting breast cancer metastasis. Using silencing RNA (siRNA) molecules to knockdown RhoC expression is a promising approach to inhibit breast cancer metastases. However, transforming anti-RhoC siRNA molecules into a viable therapy remains a challenge due to the lack of a biocompatible carrier that can selectively deliver the RNA cargo into breast cancer cells. We report the use of a degradable, pH-sensitive, β-cyclodextrin (βCD)-based polymeric carrier that condenses anti-RhoC siRNA forming "smart" particles. These smart anti-RhoC particles were efficiently internalized, successfully escaped the endosome, and delivered the RNA cargo into the cytoplasm of SUM149 and MDA-MB-231 breast cancer cells. Our results show that anti-RhoC particles used at a low N/P ratio of 2.5/1 suppressed RhoC protein levels by 100% and 90% in SUM149 and MDA-MB-231 cells, respectively. Further, anti-RhoC particles inhibited the invasion, motility, and migration of SUM149 and MDA-MB-231 cells by 40-47%, 57-60%, and 61.5-73%, respectively. Smart particles encapsulating the scrambled siRNA sequence did not affect RhoC protein expression or the invasion, motility, and migration of SUM149 and MDA-MB-231 cells, which indicate the biocompatibility of the polymeric carrier and selectivity of the observed RhoC knockdown. These results collectively indicate the therapeutic potential of smart anti-RhoC particles in arresting the metastatic spread of breast cancer cells.

  16. 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...

  17. 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...

  18. Beating Breast Cancer

    Science.gov (United States)

    ... of this page please turn JavaScript on. Feature: Breast Cancer Beating Breast Cancer Past Issues / Winter 2017 Table of Contents Melanie ... Her mother had died at age 49 of breast cancer after three battles with the disease. Ovarian cancer ...

  19. Update of the National Surgical Adjuvant Breast and Bowel Project Study of Tamoxifen and Raloxifene (STAR) P-2 Trial: Preventing breast cancer

    National Research Council Canada - National Science Library

    Vogel, Victor G; Costantino, Joseph P; Wickerham, D Lawrence; Cronin, Walter M; Cecchini, Reena S; Atkins, James N; Bevers, Therese B; Fehrenbacher, Louis; Pajon, Eduardo R; Wade, 3rd, James L; Robidoux, André; Margolese, Richard G; James, Joan; Runowicz, Carolyn D; Ganz, Patricia A; Reis, Steven E; McCaskill-Stevens, Worta; Ford, Leslie G; Jordan, V Craig; Wolmark, Norman

    2010-01-01

    .... The FDA approved the SERM raloxifene for breast cancer risk reduction following its demonstrated effectiveness in preventing invasive breast cancer in the Study of Tamoxifen and Raloxifene (STAR...

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

    National Research Council Canada - National Science Library

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

    2011-01-01

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

  1. Tamoxifen for Breast Cancer

    Directory of Open Access Journals (Sweden)

    A Karn

    2010-03-01

    Full Text Available Breast cancer is one of the common cancers. Hormonal therapy along with surgery, chemotherapy, radiotherapy and targeted therapy are vital modalities for the management of breast cancer. Tamoxifen has been the most widely used hormonal therapy for more than two decades. In this article we review the benefits, dose, duration and timing of Tamoxifen therapy in patients with breast cancer. Keywords: breast cancer, hormonal therapy, tamoxifen.

  2. Targeting CD44-STAT3 signaling by Gemini vitamin D analog leads to inhibition of invasion in basal-like breast cancer.

    Science.gov (United States)

    So, Jae Young; Smolarek, Amanda K; Salerno, David M; Maehr, Hubert; Uskokovic, Milan; Liu, Fang; Suh, Nanjoo

    2013-01-01

    CD44, a transmembrane glycoprotein, is a major receptor for extracellular proteins involved in invasion and metastasis of human cancers. We have previously demonstrated that the novel Gemini vitamin D analog BXL0124 [1α,25-dihydroxy-20R-21(3-hydroxy-3-deuteromethyl-4,4,4-trideuterobutyl)-23-yne-26,27-hexafluro-cholecalciferol] repressed CD44 expression in MCF10DCIS.com basal-like human breast cancer cells and inhibited MCF10DCIS xenograft tumor growth. In the present study, we investigated potential factors downstream of CD44 and the biological role of CD44 repression by BXL0124 in MCF10DCIS cells. The treatment with Gemini vitamin D BXL0124 decreased CD44 protein level, suppressed STAT3 signaling, and inhibited invasion and proliferation of MCF10DCIS cells. The interaction between CD44 and STAT3 was determined by co-immunoprecipitation. CD44 forms a complex with STAT3 and Janus kinase 2 (JAK2) to activate STAT3 signaling, which was inhibited by BXL0124 in MCF10DCIS cells. The role of CD44 in STAT3 signaling and invasion of MCF10DCIS cells was further determined by the knockdown of CD44 using small hairpin RNA in vitro and in vivo. MCF10DCIS cell invasion was markedly decreased by the knockdown of CD44 in vitro. The knockdown of CD44 also significantly decreased mRNA expression levels of invasion markers, matrix metalloproteinases (MMPs) and urokinase plasminogen activator (uPA), in MCF10DCIS cells. In MCF10DCIS xenograft tumors, CD44 knockdown decreased tumor size and weight as well as invasion markers. The present study identifies STAT3 as an important signaling molecule interacting with CD44 and demonstrates the essential role of CD44-STAT3 signaling in breast cancer invasion. It also suggests that repression of CD44-STAT3 signaling is a key molecular mechanism in the inhibition of breast cancer invasion by the Gemini vitamin D analog BXL0124.

  3. Targeting CD44-STAT3 signaling by Gemini vitamin D analog leads to inhibition of invasion in basal-like breast cancer.

    Directory of Open Access Journals (Sweden)

    Jae Young So

    Full Text Available CD44, a transmembrane glycoprotein, is a major receptor for extracellular proteins involved in invasion and metastasis of human cancers. We have previously demonstrated that the novel Gemini vitamin D analog BXL0124 [1α,25-dihydroxy-20R-21(3-hydroxy-3-deuteromethyl-4,4,4-trideuterobutyl-23-yne-26,27-hexafluro-cholecalciferol] repressed CD44 expression in MCF10DCIS.com basal-like human breast cancer cells and inhibited MCF10DCIS xenograft tumor growth. In the present study, we investigated potential factors downstream of CD44 and the biological role of CD44 repression by BXL0124 in MCF10DCIS cells.The treatment with Gemini vitamin D BXL0124 decreased CD44 protein level, suppressed STAT3 signaling, and inhibited invasion and proliferation of MCF10DCIS cells. The interaction between CD44 and STAT3 was determined by co-immunoprecipitation. CD44 forms a complex with STAT3 and Janus kinase 2 (JAK2 to activate STAT3 signaling, which was inhibited by BXL0124 in MCF10DCIS cells. The role of CD44 in STAT3 signaling and invasion of MCF10DCIS cells was further determined by the knockdown of CD44 using small hairpin RNA in vitro and in vivo. MCF10DCIS cell invasion was markedly decreased by the knockdown of CD44 in vitro. The knockdown of CD44 also significantly decreased mRNA expression levels of invasion markers, matrix metalloproteinases (MMPs and urokinase plasminogen activator (uPA, in MCF10DCIS cells. In MCF10DCIS xenograft tumors, CD44 knockdown decreased tumor size and weight as well as invasion markers.The present study identifies STAT3 as an important signaling molecule interacting with CD44 and demonstrates the essential role of CD44-STAT3 signaling in breast cancer invasion. It also suggests that repression of CD44-STAT3 signaling is a key molecular mechanism in the inhibition of breast cancer invasion by the Gemini vitamin D analog BXL0124.

  4. Prognostic significance of equivocal human epidermal growth factor receptor 2 results and clinical utility of alternative chromosome 17 genes in patients with invasive breast cancer: A cohort study.

    Science.gov (United States)

    Sneige, Nour; Hess, Kenneth R; Multani, Asha S; Gong, Yun; Ibrahim, Nuhad K

    2017-04-01

    The 2013 testing guidelines for determining the human epidermal growth factor receptor 2 (HER2) status include new cutoff points for the HER2/chromosome enumeration probe 17 (CEP17) ratio and the average HER2 copy number per cell, and they recommend using a reflex test with alternative chromosome 17 probes (Ch17Ps) to resolve equivocal HER2 results. This study sought to determine the clinical utility of alternative Ch17Ps in equivocal cases and the effects of equivocal results and/or a change in the HER2 status on patients' outcomes. The University of Texas MD Anderson Cancer Center database of HER2 dual-probe fluorescence in situ hybridization results from 2000 to 2010 was searched for cases of invasive breast cancer with HER2/CEP17 ratios Cancer 2017;123:1115-1123. © 2016 American Cancer Society. © 2016 American Cancer Society.

  5. Danish Breast Cancer Cooperative Group

    DEFF Research Database (Denmark)

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

    2016-01-01

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

  6. The Prognostic Value of the Proliferation Marker Phosphohistone H3 (PPH3) in Luminal, Basal-Like and Triple Negative Phenotype Invasive Lymph Node-Negative Breast Cancer

    Science.gov (United States)

    Skaland, Ivar; Janssen, Emiel A. M.; Gudlaugsson, Einar; Guo, Lydia Hui Ru; Baak, Jan P. A.

    2009-01-01

    Purpose: Prognostic comparison of phosphohistone-H3 (PPH3) with Cytokeratin 5/6 and/or 14 positive (= basal-CK), triple (ER, PR, HER2)-negative (= TNP) and basal-like (= TNP and basal-CK positive) phenotype in invasive breast cancers. Patients and Methods: Classical variables, PPH3, ER, PR, basal-CK and HER2 in 240 T1–2N0M0 patients under 71 years. Results: TNP and basal-like cancers had higher PPH3 expression than the other cancers (mean 48 versus 11, P < 0.001). Fifteen percent of the patients in the whole group, but 32–38% of TNP and basal-like cancers recurred.With multivariate analysis, PPH3 < 13 (n = 156) versus ≥ 13 (n = 84 = 35% of all cases) was the strongest and only prognosticator (10-year survival 96% and 64%, P ≤ 0.001, Hazard ratio = 9.0). Conclusion: PPH3 is the strongest prognosticators in luminal, Triple negative and basal-like T1–2N0M0 invasive breast cancers. PMID:19633363

  7. Family History of Breast Cancer, Breast Density, and Breast Cancer Risk in a U.S. Breast Cancer Screening Population.

    Science.gov (United States)

    Ahern, Thomas P; Sprague, Brian L; Bissell, Michael C S; Miglioretti, Diana L; Buist, Diana S M; Braithwaite, Dejana; Kerlikowske, Karla

    2017-06-01

    Background: The utility of incorporating detailed family history into breast cancer risk prediction hinges on its independent contribution to breast cancer risk. We evaluated associations between detailed family history and breast cancer risk while accounting for breast density.Methods: We followed 222,019 participants ages 35 to 74 in the Breast Cancer Surveillance Consortium, of whom 2,456 developed invasive breast cancer. We calculated standardized breast cancer risks within joint strata of breast density and simple (1st-degree female relative) or detailed (first-degree, second-degree, or first- and second-degree female relative) breast cancer family history. We fit log-binomial models to estimate age-specific breast cancer associations for simple and detailed family history, accounting for breast density.Results: Simple first-degree family history was associated with increased breast cancer risk compared with no first-degree history [Risk ratio (RR), 1.5; 95% confidence interval (CI), 1.0-2.1 at age 40; RR, 1.5; 95% CI, 1.3-1.7 at age 50; RR, 1.4; 95% CI, 1.2-1.6 at age 60; RR, 1.3; 95% CI, 1.1-1.5 at age 70). Breast cancer associations with detailed family history were strongest for women with first- and second-degree family history compared with no history (RR, 1.9; 95% CI, 1.1-3.2 at age 40); this association weakened in higher age groups (RR, 1.2; 95% CI, 0.88-1.5 at age 70). Associations did not change substantially when adjusted for breast density.Conclusions: Even with adjustment for breast density, a history of breast cancer in both first- and second-degree relatives is more strongly associated with breast cancer than simple first-degree family history.Impact: Future efforts to improve breast cancer risk prediction models should evaluate detailed family history as a risk factor. Cancer Epidemiol Biomarkers Prev; 26(6); 938-44. ©2017 AACR. ©2017 American Association for Cancer Research.

  8. Magnetic Resonance Arterial Spin Tagging for Non-Invasive Pharmacokinetic Analysis of Breast Cancer

    Science.gov (United States)

    2000-10-01

    116 *bo Z C’ o U U) 0 0 C- v Ed tc)iý to rn CPg 1170 of the breast. The ROIs with the size of 35 mm2 have been identified from all 10 slices acquired...input(’The size of the P files (in Bytes) is: ’); fid = fopen(pfile,’r’); [B, count] = fread( fid ,(rawSize/2), ’short’); % fclose( fid ); count Pg. 167

  9. The lipid-reactive oxygen species phenotype of breast cancer. Raman spectroscopy and mapping, PCA and PLSDA for invasive ductal carcinoma and invasive lobular carcinoma. Molecular tumorigenic mechanisms beyond Warburg effect.

    Science.gov (United States)

    Surmacki, Jakub; Brozek-Pluska, Beata; Kordek, Radzislaw; Abramczyk, Halina

    2015-04-07

    Vibrational signatures of human breast tissue (invasive ductal carcinoma and invasive lobular carcinoma) were used to identify, characterize and discriminate structures in normal (noncancerous) and cancerous tissues by confocal Raman imaging, Raman spectroscopy and IR spectroscopy. The most important differences between normal and cancerous tissues were found in regions characteristic for vibrations of carotenoids, fatty acids, proteins, and interfacial water. Particular attention was paid to the role played by unsaturated fatty acids and their derivatives. K-means clustering and basis analysis followed by PCA and PLSDA is employed to analyze Raman spectroscopic maps of human breast tissue and for a statistical analysis of the samples (82 patients, 164 samples). Raman maps successfully identify regions of carotenoids, fatty acids, and proteins. The intensities, frequencies and profiles of the average Raman spectra differentiate the biochemical composition of normal and cancerous tissues. The paper demonstrates that Raman imaging has reached a clinically relevant level in regard to breast cancer diagnosis applications. The sensitivity and specificity obtained directly from PLSLD and cross validation are equal to 90.5% and 84.8% for calibration and 84.7% and 71.9% for cross-validation respectively.

  10. Predictors of invasive breast cancer and lymph node involvement in ductal carcinoma in situ initially diagnosed by vacuum-assisted breast biopsy: experience of 733 cases.

    Science.gov (United States)

    Trentin, Chiara; Dominelli, Valeria; Maisonneuve, Patrick; Menna, Simona; Bazolli, Barbara; Luini, Alberto; Cassano, Enrico

    2012-10-01

    To predict presence of invasive component and nodal involvement in women diagnosed preoperatively with ductal carcinoma in situ (DCIS) by vacuum-assisted breast biopsy (VABB). We retrospectively analyzed 733 patients with preoperatively diagnosed DCIS, investigating the association of clinical-radiological variables with invasive component and nodal involvement. Mammographic size >20 mm and residual lesion on post-VABB mammogram were related to invasive component (both p 20 mm with nodal involvement, both highly significant. Older age, lesion <20 mm, and no residual lesion predict absence of invasion and no nodal involvement in VABB-diagnosed DCIS. However it would be imprudent to routinely forego sentinel node biopsy in such patients as non-negligible proportions of them have invasive disease. Copyright © 2012 Elsevier Ltd. All rights reserved.

  11. Adverse prognostic value of peritumoral vascular invasion: is it abrogated by adequate endocrine adjuvant therapy? Results from two International Breast Cancer Study Group randomized trials of chemoendocrine adjuvant therapy for early breast cancer

    Science.gov (United States)

    Viale, G.; Giobbie-Hurder, A.; Gusterson, B. A.; Maiorano, E.; Mastropasqua, M. G.; Sonzogni, A.; Mallon, E.; Colleoni, M.; Castiglione-Gertsch, M.; Regan, M. M.; Brown, R. W.; Golouh, R.; Crivellari, D.; Karlsson, P.; Öhlschlegel, C.; Gelber, R. D.; Goldhirsch, A.; Coates, A. S.

    2010-01-01

    Background: Peritumoral vascular invasion (PVI) may assist in assigning optimal adjuvant systemic therapy for women with early breast cancer. Patients and methods: Patients participated in two International Breast Cancer Study Group randomized trials testing chemoendocrine adjuvant therapies in premenopausal (trial VIII) or postmenopausal (trial IX) node-negative breast cancer. PVI was assessed by institutional pathologists and/or central review on hematoxylin–eosin-stained slides in 99% of patients (analysis cohort 2754 patients, median follow-up >9 years). Results: PVI, present in 23% of the tumors, was associated with higher grade tumors and larger tumor size (trial IX only). Presence of PVI increased locoregional and distant recurrence and was significantly associated with poorer disease-free survival. The adverse prognostic impact of PVI in trial VIII was limited to premenopausal patients with endocrine-responsive tumors randomized to therapies not containing goserelin, and conversely the beneficial effect of goserelin was limited to patients whose tumors showed PVI. In trial IX, all patients received tamoxifen: the adverse prognostic impact of PVI was limited to patients with receptor-negative tumors regardless of chemotherapy. Conclusion: Adequate endocrine adjuvant therapy appears to abrogate the adverse impact of PVI in node-negative disease, while PVI may identify patients who will benefit particularly from adjuvant therapy. PMID:19633051

  12. Breast cancer staging

    Science.gov (United States)

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

  13. HEREDITARY BREAST CANCER

    Directory of Open Access Journals (Sweden)

    E. M. Bit-Sava

    2013-01-01

    Full Text Available Hereditary breast cancer occurs in 5–20 % of cases and it is associated with inherited mutations in particular genes, such as BRCA1 и BRCA2 in most cases. The CHEK2, PTEN, TP53, ATM, RAD51, BLM, PALB2, Nbs genes are associated with low and median risks ofdeveloping breast cancer. Molecular genetic studies identify germinal mutations underlying hereditary breast cancer. In most cases hereditary breast cancer refers to triple-negative phenotype, which is the most aggressive type of breast cancer, that does not express the genes for estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 (HER2. The review presents the diagnostic and treatment methods of hereditary breast cancer. Clinical-morphological aspects allow the new diagnostic and treatment methods of hereditary breast cancer to be identified. Poly (ADP-ribose polymerase (PARP inhibitors demonstrate the potential for effective treatment of BRCA-associated breast cancer.

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

    DEFF Research Database (Denmark)

    Sawyer, Elinor; Roylance, Rebecca; Petridis, Christos

    2014-01-01

    Invasive lobular breast cancer (ILC) accounts for 10-15% of all invasive breast carcinomas. It is generally ER positive (ER+) and often associated with lobular carcinoma in situ (LCIS). Genome-wide association studies have identified more than 70 common polymorphisms that predispose to breast can...

  15. [Breast cancer: new therapeutic strategies].

    Science.gov (United States)

    Espie, M

    1998-12-12

    NEED FOR NEW CHEMOTHERAPY AGENTS: Metastasic breast cancer is an excellent model for studying anticancer agents: chemotherapy or hormonotherapy or compounds modifying the organism's response. If no adjuvant treatment is given after locoregional treatment of breast cancer, metastasis will develop within 10 years in 30% of the patients free of initial nodal invasion and within 5 years in 50% of the patients with initial nodal invasion. ADJUVANT TREATMENTS: Hormonotherapy and chemotherapy reduce mortality due to breast cancer by 10%. New adjuvant agents have been recently introduced. Taxans (docetaxel, paclitaxel) are the most active molecules since antracyclines. New aromataase inhibitors include letrozole and anastrozole. Their efficacy has been demonstrated in phase II and phase III trials, allowing their experimentation as adjuvant treatments.

  16. Breast Cancer and Infertility

    Directory of Open Access Journals (Sweden)

    Guluzar Arzu Turan

    2015-09-01

    Full Text Available Breast cancer is the most common malignancy among women and may accompany infertility. The relationship between infertility treatment and breast cancer has not yet been proven. However, estrogen exposure is well known to cause breast cancer. Recent advances in treatment options have provided young patients with breast cancer a chance of being mother [Archives Medical Review Journal 2015; 24(3.000: 317-323

  17. Breast Cancer (For Kids)

    Science.gov (United States)

    ... Staying Safe Videos for Educators Search English Español Breast Cancer KidsHealth / For Kids / Breast Cancer What's in this ... for it when they are older. What Is Breast Cancer? The human body is made of tiny building ...

  18. Markers of progression in early-stage invasive breast cancer: a predictive immunohistochemical panel algorithm for distant recurrence risk stratification.

    Science.gov (United States)

    Aleskandarany, Mohammed A; Soria, D; Green, A R; Nolan, C; Diez-Rodriguez, Maria; Ellis, I O; Rakha, E A

    2015-06-01

    Accurate distant metastasis (DM) prediction is critical for risk stratification and effective treatment decisions in breast cancer (BC). Many prognostic markers/models based on tissue marker studies are continually emerging using conventional statistical approaches analysing complex/dimensional data association with DM/poor prognosis. However, few of them have fulfilled satisfactory evidences for clinical application. This study aimed at building DM risk assessment algorithm for BC patients. A well-characterised series of early invasive primary operable BC (n = 1902), with immunohistochemical expression of a panel of biomarkers (n = 31) formed the material of this study. Decision tree algorithm was computed using WEKA software, utilising quantitative biomarkers' expression and the absence/presence of distant metastases. Fifteen biomarkers were significantly associated with DM, with six temporal subgroups characterised based on time to development of DM ranging from 15 years of follow-up. Of these 15 biomarkers, 10 had a significant expression pattern where Ki67LI, HER2, p53, N-cadherin, P-cadherin, PIK3CA and TOMM34 showed significantly higher expressions with earlier development of DM. In contrast, higher expressions of ER, PR and BCL2 were associated with delayed occurrence of DM. DM prediction algorithm was built utilising cases informative for the 15 significant markers. Four risk groups of patients were characterised. Three markers p53, HER2 and BCL2 predicted the probability of DM, based on software-generated cut-offs, with a precision rate of 81.1 % for positive predictive value and 77.3 %, for the negative predictive value. This algorithm reiterates the reported prognostic values of these three markers and underscores their central biological role in BC progression. Further independent validation of this pruned panel of biomarkers is therefore warranted.

  19. What are safe margins of resection for invasive and in situ breast cancer?

    Science.gov (United States)

    Revesz, Elizabeth; Khan, Seema A

    2011-09-01

    Adequate surgical margins in breast-conserving surgery are an important predictor of local recurrence (LR) rates. The definition of tumor-free margins in National Surgical Adjuvant Breast and Bowel Project (NSABP) trials requires that tumor cells do not touch ink, but subsequent retrospective single-institution studies have suggested that wider margins confer greater protection against LR. Particularly wide margins have been proposed for ductal carcinoma in situ. However, wider margin requirements lead to higher re-excision rates, with attendant economic, psychological, and cosmetic costs, and perhaps increased mastectomy rates. Juxtaposed against these concerns about optimal margin width, a meta-analysis of clinical trials has demonstrated the survival value of minimizing LR. We are therefore at a juncture where a reduction of LR may be achieved by tumor resection with wide margins, but data regarding optimal margin width are conflicting and the risk/benefit balance of tumorectomy with wide margins has not been demonstrated. A randomized trial of reexcision for close margins inserted into trials of systemic therapy could be considered but seems unlikely. Alternatively, detailed longitudinal data need to balance the value and the cost of wide margins. Until better data are available, the desirable margin width will vary depending on individual circumstances, including age, histology, and patient preference.

  20. The role of pre-invasive disease in overdiagnosis: A microsimulation study comparing mass screening for breast cancer and cervical cancer

    NARCIS (Netherlands)

    P.A. van Luijt (Paula); K. Rozemeijer (Kirsten); S.K. Naber (Steffie); E.A.M. Heijnsdijk (Eveline); J.M. van Rosmalen (Joost); M. van Ballegooijen (Marjolein); H.J. de Koning (Harry)

    2016-01-01

    textabstractObjective: Although early detection of cancer through screening can prevent cancer deaths, a drawback of screening is overdiagnosis. Overdiagnosis has been much debated in breast cancer screening, but less so in cervical cancer screening. We examined the impact of overdiagnosis by

  1. Computer-aided Diagnosis-generated Kinetic Features of Breast Cancer at Preoperative MR Imaging: Association with Disease-free Survival of Patients with Primary Operable Invasive Breast Cancer.

    Science.gov (United States)

    Kim, Jin Joo; Kim, Jin You; Kang, Hyun Jung; Shin, Jong Ki; Kang, Taewoo; Lee, Seok Won; Bae, Young Tae

    2017-07-01

    Purpose To retrospectively investigate the relationship between the kinetic features of breast cancer assessed with computer-aided diagnosis (CAD) at preoperative magnetic resonance (MR) imaging and disease-free survival in patients with primary operable invasive breast cancer. Materials and Methods This retrospective study was approved by the institutional review board. The requirement to obtain informed consent was waived. The authors identified 329 consecutive women (mean age, 52.9 years; age range, 32-88 years) with newly diagnosed invasive breast cancer who had undergone preoperative MR imaging and surgery between January 2012 and February 2013. All MR images were retrospectively reviewed by using a commercially available CAD system, and the following kinetic parameters were noted for each lesion: peak enhancement (highest pixel signal intensity in the first series obtained after administration of contrast material), angio-volume (total volume of the enhancing lesion), and delayed enhancement profiles (the proportions of washout, plateau, and persistently enhancing component within a tumor). Cox proportional hazards modeling was used to identify the relationship between CAD-generated kinetics and disease-free survival after adjusting for clinical-pathologic variables. Results A total of 36 recurrences developed at a median follow-up of 50 months (range, 15-55 months). CAD-measured peak enhancement at preoperative MR imaging enabled differentiation between patients with and patients without recurrence (area under the receiver operating characteristic curve = 0.728; 95% confidence interval [CI]: 0.676, 0.775; P < .001). Multivariate Cox analysis showed that a higher peak enhancement (hazard ratio [HR] = 1.001; 95% CI: 1.000, 1.002; P = .004), a higher washout component (HR = 1.029; 95% CI: 1.005, 1.054; P = .017), and lymphovascular invasion at histopathologic examination (HR = 3.011; 95% CI: 1.302, 6.962; P = .010) were associated with poorer disease

  2. Screening for Breast Cancer.

    Science.gov (United States)

    Niell, Bethany L; Freer, Phoebe E; Weinfurtner, Robert Jared; Arleo, Elizabeth Kagan; Drukteinis, Jennifer S

    2017-11-01

    The goal of screening is to detect breast cancers when still curable to decrease breast cancer-specific mortality. Breast cancer screening in the United States is routinely performed with mammography, supplemental digital breast tomosynthesis, ultrasound, and/or MR imaging. This article aims to review the most commonly used breast imaging modalities for screening, discuss how often and when to begin screening with specific imaging modalities, and examine the pros and cons of screening. By the article's end, the reader will be better equipped to have informed discussions with patients and medical professionals regarding the benefits and disadvantages of breast cancer screening. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Breast asymmetry and predisposition to breast cancer

    OpenAIRE

    Scutt, D; Lancaster, GA; Manning, JT

    2006-01-01

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

  4. p300 and p53 levels determine activation of HIF-1 downstream targets in invasive breast cancer

    NARCIS (Netherlands)

    Vleugel, M.M.; Shvarts, D.; Wall, E. van der; Diest, P.J. van

    2006-01-01

    In previous studies, we noted that overexpression of hypoxia-inducible factor (HIF)–1a in breast cancer, especially the diffuse form, does not always lead to functional activation of its downstream genes. Transcriptional activity of HIF-1 may be repressed by p53 through competition

  5. Synergistic effects of curcumin with emodin against the proliferation and invasion of breast cancer cells through upregulation of miR-34a.

    Science.gov (United States)

    Guo, Jiaoli; Li, Wenping; Shi, Hongliu; Xie, Xinhua; Li, Laisheng; Tang, Hailin; Wu, Minqing; Kong, Yanan; Yang, Lu; Gao, Jie; Liu, Peng; Wei, Weidong; Xie, Xiaoming

    2013-10-01

    Curcumin, a biphenyl compound derived from rhizome, is a powerful anti-cancer agent. Emodin is an active component isolated from the root and rhizome of Rheum palmatum that has been widely used in traditional Chinese medicine for the treatment of various diseases. Currently, there are no studies examining the effect of curcumin in combination with emodin on tumor cell growth. In this study, we report for the first time that combined curcumin and emodin administration synergistically inhibits proliferation (MTT assay), survival (flow cytometry), and invasion (transwell migration assay) of breast cancer cells. Synergism is determined by the Chou-Talalay method. Moreover, we demonstrate that miR-34a is upregulated by curcumin and emodin. This microRNA helps mediate the anti-tumor effects of curcumin and emodin by downregulating Bcl-2 and Bmi-1. Our results not only provide insight into the mechanism of synergy between curcumin and emodin in breast cancer cells, but also suggest a new and potentially useful approach for breast cancer therapy.

  6. Multiplication of Chromosome 17 Centromere Is Associated with Prognosis in Patients with Invasive Breast Cancers Exhibiting Normal HER2 and TOP2A Status.

    Science.gov (United States)

    Kim, Aeri; Shin, Hyung Chan; Bae, Young Kyung; Kim, Min Kyoung; Kang, Su Hwan; Lee, Soo Jung; Lee, Eun Hee

    2012-03-01

    This study aimed to investigate the clinical significance of chromosome 17 centromere (CEP17) multiplication (increased copy number of CEP17) related to human epidermal growth factor receptor 2 (HER2) and topoisomerase II alpha (TOP2A) status in patients with invasive breast cancer. We constructed tissue microarrays using 594 invasive breast cancer samples and performed single-color silver-enhanced in situ hybridization (SISH) assay for HER2, TOP2A, and CEP17 to assess for copy number aberrations. The association of CEP17 multiplication with patient survival was analyzed according to HER2 and TOP2A status. Among 567 informative cases, HER2 amplification was noted in 22.8%, TOP2A amplification in 8.3% and TOP2A deletion in 11.1%. CEP17 multiplication was identified in 33.2% and was significantly associated with worse overall survival (OS) (p=0.02) and disease-free survival (DFS) (p=0.02). CEP17 multiplication correlated with patient survival in patients with normal TOP2A or non-amplified HER2 status, but the prognostic significance was lost in those with altered TOP2A or amplified HER2. On multivariate analyses, CEP17 multiplication was an independent prognostic factor for poorer OS (p=0.02) and DFS (p=0.01) in patients with normal TOP2A and non-amplified HER2. CEP17 multiplication was identified as a promising prognostic marker in patients with invasive breast cancer exhibiting either non-amplified HER2 or normal TOP2A status.

  7. Breast Cancer Rates by State

    Science.gov (United States)

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

  8. Computed tomography of the breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Soo Young; Lee, Yul; Bae, Sang Hoon; Yoon, Jong Sup; Lee, Ki Chu [Hallym University Medical Center, Seoul (Korea, Republic of)

    1985-12-15

    The indication of computed tomography for the breast lesion are 1) Unusually extensive or small breast caused technical difficulties in performing mammograms. 2) Questionable mammographic findings, especially in dense proliferative breast parenchyme. 3) Microcancer. 4) Suspicious regional lymph node enlargement or invasive of the chest wall by breast cancer. The diagnosis of breast CT in breast cancer is based on pathologic anatomic changes and characteristic increase of mean CT No. of lesion following contrast enhancement. Authors analysed CT of the 34 patients who were clinically suspected breast cancer, and compared with mammography. The results are as follows: 1. Pathological diagnosis of 34 cases were 27 cases of breast cancer, 4 cases of fibrocystic disease, 2 cases of fibroadenoma, and 1 case of intraductal papilloma. The diagnostic accuracy of CT in 27 breast cancer was 93% (25 cases) and mammography 71% (19 case). 2. Correct diagnosis of CT in 7 benign breast disease is in 5 cases and mammography in 5 cases. 3. The most important finding of CT in breast cancer is characteristic increase of CT No. of lesion following contrast enhancement (200 ml, 65%): over average 50 HU in 19 cases of 27 breast cancers, 30-50 HU in a 6 cases, 20-30 HU in 2 cases with tumor necrosis. 4. Computed with mammography, other more valuable CT findings of breast cancer are axillary lymph node enlargement and adjacentic pectoral muscle invasion. 5. In conclusion, breast CT is considered as valuable diagnostic tool in evaluation of breast cancer, but not of benign breast disease.

  9. Dynamics of cancerous tissue correlates with invasiveness

    Science.gov (United States)

    West, Ann-Katrine Vransø; Wullkopf, Lena; Christensen, Amalie; Leijnse, Natascha; Tarp, Jens Magelund; Mathiesen, Joachim; Erler, Janine Terra; Oddershede, Lene Broeng

    2017-03-01

    Two of the classical hallmarks of cancer are uncontrolled cell division and tissue invasion, which turn the disease into a systemic, life-threatening condition. Although both processes are studied, a clear correlation between cell division and motility of cancer cells has not been described previously. Here, we experimentally characterize the dynamics of invasive and non-invasive breast cancer tissues using human and murine model systems. The intrinsic tissue velocities, as well as the divergence and vorticity around a dividing cell correlate strongly with the invasive potential of the tissue, thus showing a distinct correlation between tissue dynamics and aggressiveness. We formulate a model which treats the tissue as a visco-elastic continuum. This model provides a valid reproduction of the cancerous tissue dynamics, thus, biological signaling is not needed to explain the observed tissue dynamics. The model returns the characteristic force exerted by an invading cell and reveals a strong correlation between force and invasiveness of breast cancer cells, thus pinpointing the importance of mechanics for cancer invasion.

  10. E-cadherin expression phenotypes associated with molecular subtypes in invasive non-lobular breast cancer: evidence from a retrospective study and meta-analysis.

    Science.gov (United States)

    Liu, Jiang-Bo; Feng, Chen-Yi; Deng, Miao; Ge, Dong-Feng; Liu, De-Chun; Mi, Jian-Qiang; Feng, Xiao-Shan

    2017-08-01

    This retrospective study and meta-analysis was designed to explore the relationship between E-cadherin (E-cad) expression and the molecular subtypes of invasive non-lobular breast cancer, especially in early-stage invasive ductal carcinoma (IDC). A total of 156 post-operative cases of early-stage IDCs were retrospectively collected for the immunohistochemistry (IHC) detection of E-cad expression. The association of E-cad expression with molecular subtypes of early-stage IDCs was analyzed. A literature search was conducted in March 2016 to retrieve publications on E-cad expression in association with molecular subtypes of invasive non-lobular breast cancer, and a meta-analysis was performed to estimate the relational statistics. E-cad was expressed in 82.7% (129/156) of early-stage IDCs. E-cad expression was closely associated with the molecular types of early-stage IDCs (P molecular subtypes were an independent factor influencing E-cad expression in early-stage IDCs. A total of 12 observational studies (including our study) were included in the meta-analysis. The meta-analytical results show a significantly greater risk of E-cad expression loss in triple-negative breast cancer (TNBC) than in other molecular subtypes (TNBC vs. luminal A: RR = 3.45, 95% CI = 2.79-4.26; TNBC vs. luminal B: RR = 2.41, 95% CI = 1.49-3.90; TNBC vs. HER2-enriched: RR = 1.95, 95% CI = 1.24-3.07). Early-stage IDCs or invasive non-lobular breast cancers with the TNBC molecular phenotype have a higher risk for the loss of E-cad expression than do tumors with non-TNBC molecular phenotypes, suggesting that E-cad expression phenotypes were closely related to molecular subtypes and further studies are needed to clarify the underlying mechanism.

  11. The prognostic value of age for invasive lobular breast cancer depending on estrogen receptor and progesterone receptor-defined subtypes: A NCDB analysis.

    Science.gov (United States)

    Liu, Jieqiong; Chen, Kai; Mao, Kai; Su, Fengxi; Liu, Qiang; Jacobs, Lisa K

    2016-02-02

    We aimed to assess the effect of age on survival according to estrogen receptor (ER) and progesterone receptor (PR)-defined lobular breast cancer subtype in a wide age range. 43,230 invasive lobular breast cancer women without comorbidities diagnosed between 2004 and 2011 in the National Cancer Database (NCDB) were analyzed. The effects of age on overall survival (OS) among different age groups were evaluated by log-rank test and Cox proportional model. Multivariate analysis showed that patients diagnosed at both young (ages had worse prognosis compared with those in the middle ages. We further analyzed the interaction between age and molecular subtype for predicting OS: in ER+PR+ subtype, the HR of OS declined with age from 1.55 (95% CI, 1.08-2.22; P = 0.019) in the group younger than 35 years to 1.38 (1.02-1.86; P = 0.036) in the 35-39 group, but increased with age to 10.1 (8.49-11.94; P 0.1); and in ER-PR+ subgroup, the HRs were similar in patients younger than 70 (P > 0.1); thus, the plots of HRs in these three subtypes remained steady until the age of 60 or 70. Our findings identified that the effect of age on OS in lobular breast cancer varied with ER/PR-defined subtypes. Personalized treatment strategies should be developed to improve outcomes of breast cancer patients with different ages and ER/PR statuses.

  12. Breast Cancer Screening in Denmark

    DEFF Research Database (Denmark)

    Jørgensen, Karsten Juhl; Gøtzsche, Peter C; Kalager, Mette

    2017-01-01

    Background: Effective breast cancer screening should detect early-stage cancer and prevent advanced disease. Objective: To assess the association between screening and the size of detected tumors and to estimate overdiagnosis (detection of tumors that would not become clinically relevant). Design......) and nonadvanced (≤20 mm) breast cancer tumors in screened and nonscreened women were measured. Two approaches were used to estimate the amount of overdiagnosis: comparing the incidence of advanced and nonadvanced tumors among women aged 50 to 84 years in screening and nonscreening areas; and comparing...... rate ratio, 1.49 [95% CI, 1.43 to 1.54]). The first estimation approach found that 271 invasive breast cancer tumors and 179 ductal carcinoma in situ (DCIS) lesions were overdiagnosed in 2010 (overdiagnosis rate of 24.4% [including DCIS] and 14.7% [excluding DCIS]). The second approach, which accounted...

  13. Study on IL-2 and CA 15-3 level as combined biomarkers in monitoring chemotherapeutic response among invasive breast cancer patients

    Science.gov (United States)

    Hameed, Ahmed Muthanna Abdul; Hamid, Auni Fatin Abdul; Shahfiza Noor, Nurul; Appalanaido, Gokula Kumar; Bariyah Sahul Hamid, Shahrul

    2017-05-01

    In Malaysia, breast cancer is the most frequent type of disease among women. This study was designed to determine the clinical usefulness of carbohydrate antigen (CA 15-3) and interleukin 2 (IL-2) levels as combined biomarkers in monitoring breast cancer patient’s response to chemotherapy. Ethical approval was obtained to recruit patients with histologically confirmed invasive ductal carcinoma (IDC) attending Oncology Clinic at Advanced Medical and Dental Institute. Whole blood was collected from 10 IDC breast cancer patients’ pre and post primary chemotherapy. Plasma was separated from the whole blood to determine the CA 15-3 level and IL-2 level using enzyme-linked immunosorbent assay (ELISA) pre and post-treatment. In addition, the histological findings, tumour stage and other patients’ data were obtained from the medical record. Findings showed that IL-2 had borderline significant changes between pre- and post-chemotherapy (p = 0.074) whereas for CA 15-3, there was insignificant differences of CA 15-3 level between pre and post-chemotherapy (p > 0.05). It was noted that only CA 15-3 level had significant correlation with tumour size. This study demonstrates that IL-2 level requires further investigation in a larger sample size to correlate its potential use as combined biomarker with CA 15-3 in monitoring response to chemotherapy.

  14. Characterization of a Test for Invasive Breast Cancer Using X-ray Diffraction of Hair - Results of a Clinical Trial

    Directory of Open Access Journals (Sweden)

    Gary L. Corino

    2009-11-01

    Full Text Available Objective: To assess the performance of a test for breast cancer utilizing synchrotron x-ray diffraction analysis of scalp hair from women undergoing diagnostic radiology assessment. Design and Setting: A double-blinded clinical trial of women who attended diagnostic radiology clinics in Australia. Patients: 1796 women referred for diagnostic radiology, with no previous history of cancer. Main Outcome Measures: Sensitivity, specificity and accuracy of the hair test analysis compared to the gold standard of imaging followed by biopsy where indicated. Results: The hair-based assay had an overall accuracy of >77% and a negative predictive value of 99%. For all women, the sensitivity of both mammography and x-ray diffraction alone was 64%, but when used together the sensitivity rose to 86%. The sensitivity of the hair test for women under the age of 70 was 74%. Conclusion: In this large population trial the association between the presence of breast cancer and an altered hair fibre X-ray diffraction pattern previously reported has been confirmed. It appears that mammography and X-ray diffraction of hair detect different populations of breast cancers, and are synergistic when used together.

  15. Association between breast cancer, breast density, and body adiposity evaluated by MRI.

    Science.gov (United States)

    Zhu, Wenlian; Huang, Peng; Macura, Katarzyna J; Artemov, Dmitri

    2016-07-01

    Despite the lack of reliable methods with which to measure breast density from 2D mammograms, numerous studies have demonstrated a positive association between breast cancer and breast density. The goal of this study was to study the association between breast cancer and body adiposity, as well as breast density quantitatively assessed from 3D MRI breast images. Breast density was calculated from 3D T1-weighted MRI images. The thickness of the upper abdominal adipose layer was used as a surrogate marker for body adiposity. We evaluated the correlation between breast density, age, body adiposity, and breast cancer. Breast density was calculated for 410 patients with unilateral invasive breast cancer, 73 patients with ductal carcinoma in situ (DCIS), and 361 controls without breast cancer. Breast density was inversely related to age and the thickness of the upper abdominal adipose layer. Breast cancer was only positively associated with body adiposity and age. Age and body adiposity are predictive of breast density. Breast cancer was not associated with breast density; however, it was associated with the thickness of the upper abdominal adipose layer, a surrogate marker for body adiposity. Our results based on a limited number of patients warrant further investigations. • MRI breast density is negatively associated with body adiposity. • MRI breast density is negatively associated with age. • Breast cancer is positively associated with body adiposity. • Breast Cancer is not associated with MRI breast density.

  16. breast cancer screening in

    African Journals Online (AJOL)

    Is Breast transillumination a viable option for breast cancer screening in limited resource settings? Authors: Elobu EA M.Med, Galukande M M M.Med, MSc, FCS, Namuguzi D M.Med, Muyinda Z M.Med. Affiliations: breast cancer screening in limited resource settings? Authors: Elobu EA1 M.Med, Galukande M1 M M.Med, ...

  17. 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...... rate of patients with interval cancer and the interval between the latest screen and diagnosis, tumour characteristics and radiological category of the interval tumours. The study focused on comparison of patients with true interval and missed interval cancer. Women with mammographically occult tumours...

  18. PRL-3 engages the focal adhesion pathway in triple-negative breast cancer cells to alter actin structure and substrate adhesion properties critical for cell migration and invasion.

    Science.gov (United States)

    Gari, Hamid H; DeGala, Gregory D; Ray, Rahul; Lucia, M Scott; Lambert, James R

    2016-10-01

    Triple-negative breast cancers (TNBCs) are among the most aggressive cancers characterized by a high propensity to invade, metastasize and relapse. We previously reported that the TNBC-specific inhibitor, AMPI-109, significantly impairs the ability of TNBC cells to migrate and invade by reducing levels of the metastasis-promoting phosphatase, PRL-3. Here, we examined the mechanisms by which AMPI-109 and loss of PRL-3 impede cell migration and invasion. AMPI-109 treatment or knock down of PRL-3 expression were associated with deactivation of Src and ERK signaling and concomitant downregulation of RhoA and Rac1/2/3 GTPase protein levels. These cellular changes led to rearranged filamentous actin networks necessary for cell migration and invasion. Conversely, overexpression of PRL-3 promoted TNBC cell invasion by upregulating matrix metalloproteinase 10, which resulted in increased TNBC cell adherence to, and degradation of, the major basement membrane component laminin. Our data demonstrate that PRL-3 engages the focal adhesion pathway in TNBC cells as a key mechanism for promoting TNBC cell migration and invasion. Collectively, these data suggest that blocking PRL-3 activity may be an effective method for reducing the metastatic potential of TNBC cells. Copyright © 2016 The Author(s). Published by Elsevier Ireland Ltd.. All rights reserved.

  19. Metaplastic Breast Cancer

    OpenAIRE

    T?rkan, Halil; G?kg?z, M. ?ehsuvar; Parlak, N. Serhat

    2016-01-01

    Metaplastic Breast Cancer (MBC) is a term referring to a heterogeneous group with malignant epithelial and mesenchymal tissue components. MBC is a rare disease, accounting for 0.2% of all breast cancers. Most MBC are triple negative cancers with poor prognosis and an aggressive clinical course. Herein, we aimed to present a 74-year-old patient with metaplastic breast cancer along with clinical, radiologic and pathologic properties.

  20. Is there different correlation with prognostic factors between “non-mass” and “mass” type invasive ductal breast cancers?

    Energy Technology Data Exchange (ETDEWEB)

    Jiang, Lei, E-mail: jiang_belinder@sina.com [Radiology Department, Beijing Hospital, Peking University, The Ministry of Health, Dahua Road 1#, East District, Beijing 100730 (China); Zhou, Yiming, E-mail: zhou_belly@sina.com [Radiology Department, Chaoyang Hospital, Capital University, Baijiazhuang Road 8#, Chaoyang District, Beijing 100020 (China); Wang, Zheng, E-mail: wangzhengmay@163.com [Pathology Department, Beijing Hospital, Peking University, The Ministry of Health, Dahua Road 1#, East District, Beijing 100730 (China); Lu, Xu, E-mail: luxu01@sina.cn [Surgery Department, Beijing Hospital, Peking University, The Ministry of Health, Dahua Road 1#, East District, Beijing 100730 (China); Chen, Min, E-mail: chenmin62@yahoo.com [Radiology Department, Beijing Hospital, Peking University, The Ministry of Health, Dahua Road 1#, East District, Beijing 100730 (China); Zhou, Cheng, E-mail: Chengzhou2000@yahoo.com [Radiology Department, Beijing Hospital, Peking University, The Ministry of Health, Dahua Road 1#, East District, Beijing 100730 (China)

    2013-09-15

    Purpose: To investigate the association between non-mass type breast cancer and common clinical–pathological prognostic factors, compared with mass type breast cancer. Materials and methods: After institutional review board approval, retrospective blind review of contrast-enhanced breast MRI was carried out for 88 histologically proven breast invasive ductal carcinoma (IDC) patients, presenting from January 2008 to December 2011. Two radiologists assessed the images of each lesion for the morphologic enhancement type [mass enhancement or non-mass-like enhancement (NMLE)] and the distribution/internal enhancement of NMLE. Two pathologists evaluated the histological grade of IDC, presence or absence of ductal carcinoma in situ (DCIS), lymph node status, presence or absence of vascular invasion, and expression status of estrogen receptor (ER)/progesterone receptor (PR)/HER-2/p53 tumor suppressor gene (p53)/Ki-67. Inter-observer agreement was assessed with kappa test. Chi-square test and Spearman rank correlation were performed to explore the associations of morphologic enhancement type with the age, lesion size and the above pathological prognostic factors Results: Inter-observer agreement was excellent, with kappa > 0.75. Morphologic enhancement type was significantly correlated with age (P = 0.02), with NMLE more commonly seen in women less than 50 y/o. The size of NMLE was larger than that of mass and, with the increase of lesion size, proportion of NMLE among the cases increased (P = 0.001). NMLE was also significantly correlated with low histologic grade of IDC (P = 0.003) and presence of DCIS (P < 0.001). There was no significant correlation between morphologic enhancement type and lymph node status, vascular invasion, ER/PR/HER-2/p53/Ki-67 status. The histological grade was higher in clumped enhancement than non-clumped (P = 0.011). There was no correlation between enhancement distribution and prognostic factors Conclusions: Non-mass type breast cancer may

  1. Epsilon-aminocaproic acid prevents high glucose and insulin induced-invasiveness in MDA-MB-231 breast cancer cells, modulating the plasminogen activator system.

    Science.gov (United States)

    Viedma-Rodríguez, Rubí; Martínez-Hernández, María Guadalupe; Flores-López, Luis Antonio; Baiza-Gutman, Luis Arturo

    2018-01-01

    Obesity and type II diabetes mellitus have contributed to the increase of breast cancer incidence worldwide. High glucose concentration promotes the proliferation of metastatic cells, favoring the activation of the plasminogen/plasmin system, thus contributing to tumor progression. The efficient formation of plasmin is dependent on the binding of plasminogen to the cell surface. We studied the effect of ε-aminocaproic acid (EACA), an inhibitor of the binding of plasminogen to cell surface, on proliferation, migration, invasion, epithelial-mesenchymal transition (EMT), and plasminogen activation system, in metastatic MDA-MB-231 breast cancer cells grown in a high glucose microenvironment and treated with insulin. MDA-MB-231 cells were treated with EACA 12.5 mmol/L under high glucose 30 mmol/L (HG) and high glucose and insulin 80 nmol/L (HG-I) conditions, evaluating: cell population growth, % of viability, migratory, and invasive abilities, as well as the expression of uPA, its receptor (uPAR), and its inhibitor (PAI-1), by real-time reverse transcription-polymerase chain reaction (RT-PCR) and Western blot, MMP-2 and MMP-9 mRNAs were evaluated by RT-PCR. Markers of EMT were evaluated by Western blot. Additionally, the presence of active uPA was studied by gel zymography, using casein-plasminogen as substrates. EACA prevented the increase in cell population, migration and invasion induced by HG and insulin, which was associated with the inhibition of EMT and the attenuation of HG- and insulin-dependent expression of uPA, uPAR, PAI-1, MMP-2, MMP-9, α-enolase (ENO A), and HCAM. The interaction of plasminogen to the cell surface and plasmin formation are mediators of the prometastasic action of hyperglycemia and insulin, potentially, EACA can be employed in the prevention and as adjuvant treatment of breast tumorigenesis promoted by hyperglycemia and insulin.

  2. Histopathological Types of Breast Cancer in Nigerian Women: A 12 ...

    African Journals Online (AJOL)

    Breast cancer occur more on the left (53.3%) than the right (45.7%). Bilateral breast cancer was found in only 0.8% of the cases. The frequency of invasive breast cancer is still very high among Nigerian women. Late presentation possible due to ignorance, alternative medicine and fear of surgery may account for this high ...

  3. 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.

  4. Technical success, technique efficacy and complications of minimally-invasive imaging-guided percutaneous ablation procedures of breast cancer: A systematic review and meta-analysis.

    Science.gov (United States)

    Mauri, Giovanni; Sconfienza, Luca Maria; Pescatori, Lorenzo Carlo; Fedeli, Maria Paola; Alì, Marco; Di Leo, Giovanni; Sardanelli, Francesco

    2017-08-01

    To systematically review studies concerning imaging-guided minimally-invasive breast cancer treatments. An online database search was performed for English-language articles evaluating percutaneous breast cancer ablation. Pooled data and 95% confidence intervals (CIs) were calculated. Technical success, technique efficacy, minor and major complications were analysed, including ablation technique subgroup analysis and effect of tumour size on outcome. Forty-five studies were analysed, including 1,156 patients and 1,168 lesions. Radiofrequency (n=577; 50%), microwaves (n=78; 7%), laser (n=227; 19%), cryoablation (n=156; 13%) and high-intensity focused ultrasound (HIFU, n=129; 11%) were used. Pooled technical success was 96% (95%CI 94-97%) [laser=98% (95-99%); HIFU=96% (90-98%); radiofrequency=96% (93-97%); cryoablation=95% (90-98%); microwave=93% (81-98%)]. Pooled technique efficacy was 75% (67-81%) [radiofrequency=82% (74-88); cryoablation=75% (51-90); laser=59% (35-79); HIFU=49% (26-74)]. Major complications pooled rate was 6% (4-8). Minor complications pooled rate was 8% (5-13%). Differences between techniques were not significant for technical success (p=0.449), major complications (p=0.181) or minor complications (p=0.762), but significant for technique efficacy (p=0.009). Tumour size did not impact on variables (p>0.142). Imaging-guided percutaneous ablation techniques of breast cancer have a high rate of technical success, while technique efficacy remains suboptimal. Complication rates are relatively low. • Imaging-guided ablation techniques for breast cancer are 96% technically successful. • Overall technique efficacy rate is 75% but largely inhomogeneous among studies. • Overall major and minor complication rates are low (6-8%).

  5. Clinical use of the Oncotype DX genomic test to guide treatment decisions for patients with invasive breast cancer

    Directory of Open Access Journals (Sweden)

    McVeigh TP

    2017-05-01

    Full Text Available Terri P McVeigh, Michael J Kerin Discipline of Surgery, Lambe Institute for Translational Research, National University of Ireland Galway, Galway, Republic of Ireland Abstract: Implementation of the Oncotype DX assay has led to a change in the manner in which chemotherapy is utilized in patients with early stage, estrogen receptor (ER-positive, node-negative breast cancer; ensuring that patients at highest risk of recurrence are prescribed systemic treatment, while at the same time sparing low-risk patients potential adverse events from therapy unlikely to influence their survival. This test generates a recurrence score between 0 and 100, which correlates with probability of distant disease recurrence. Patients with low-risk recurrence scores (0–17 are unlikely to derive significant survival benefit with adjuvant chemotherapy and hormonal agents derived from using adjuvant hormonal therapy only. Conversely, adjuvant chemotherapy has been shown to significantly improve survival in patients with high-risk recurrence scores (≥31. Trials are ongoing to determine how best to manage patients with recurrence scores in the intermediate range. This review outlines the introduction and impact of Oncotype DX testing on practice; ongoing clinical trials investigating its utility; and challenging clinical scenarios where the absolute recurrence score may require careful interpretation. We also performed a bibliometric analysis of publications on the topics of breast cancer and Oncotype DX as a surrogate marker of acceptability and incorporation of the assay into the management of patients with breast cancer. Keywords: Oncotype DX, gene expression profiling, personalized medicine, precision medicine, breast cancer

  6. Gold nanoparticle-conjugated quercetin inhibits epithelial-mesenchymal transition, angiogenesis and invasiveness via EGFR/VEGFR-2-mediated pathway in breast cancer.

    Science.gov (United States)

    Balakrishnan, S; Bhat, F A; Raja Singh, P; Mukherjee, S; Elumalai, P; Das, S; Patra, C R; Arunakaran, J

    2016-12-01

    Epidermal growth factor plays a critical role in breast malignancies by enhancing cell proliferation, invasion, angiogenesis and metastasis. Epithelial-mesenchymal transition (EMT) is a crucial process by which epithelial cells lose polarity and acquire migratory mesenchymal properties. Gold nanoparticles are an efficient drug delivery vehicle for carrying chemotherapeutic agents to target cancer cells and quercetin is an anti-oxidative flavonoid known with potent anti-malignant cell activity. Cell viability was assessed by MTT assay, and protein expression was examined by Western blotting and immunocytochemistry. Cell invasion was monitored using invasion chambers, and cell migration was analysed by scratch wound-healing assay. In vitro and ex vivo angiogenesis studies were performed by capillary-like tube formation assay and chick embryo angiogenesis assay (CEA). 7,12-dimethylbenz(a)anthracene (DMBA) induced mammary carcinoma in Sprague-Dawley rats. We observed a significant reduction in protein expression of vimentin, N-cadherin, Snail, Slug, Twist, MMP-2, MMP-9, p-EGFR, VEGFR-2, p-PI3K, Akt and p-GSK3β, and enhanced E-cadherin protein expression in response to AuNPs-Qu-5 treatment. AuNPs-Qu-5 inhibited migration and invasion of MCF-7 and MDA-MB-231 cells compared to free quercetin. AuNPs-Qu-5-treated HUVECs had reduced cell viability and capillary-like tube formation. In vitro and in vivo angiogenesis assays showed that AuNPs-Qu-5 suppressed tube and new blood vessel formation. Treatment with AuNPs-Qu-5 impeded tumour growth in DMBA-induced mammary carcinoma in SD rats compared to treatment with free quercetin. Our results suggest that AuNPs-Qu-5 inhibited EMT, angiogenesis and metastasis of the breast cancer cells tested by targeting the EGFR/VEGFR-2 signalling pathway. © 2016 John Wiley & Sons Ltd.

  7. Low dose of kaempferol suppresses the migration and invasion of triple-negative breast cancer cells by downregulating the activities of RhoA and Rac1.

    Science.gov (United States)

    Li, Shoushan; Yan, Ting; Deng, Rong; Jiang, Xuesong; Xiong, Huaping; Wang, Yuan; Yu, Qiao; Wang, Xiaohua; Chen, Cheng; Zhu, Yichao

    2017-01-01

    Triple-negative breast cancer (TNBC) is an especially aggressive and hard-to-treat disease. Although the anticancer role of kaempferol has been reported in breast cancer, the effect of kaempferol on TNBC remains unclear. This experiment investigated the migration-suppressive role of a low dose of kaempferol in TNBC cells. Wound-healing assays and cell invasion assays were used to confirm the migration and invasion of cells treated with kaempferol or transfected indicated constructs. We evaluated the activations of RhoA, Rac1 and Cdc42 in TNBC cells with a Rho activation assay. A panel of inhibitors of estrogen receptor/progesterone receptor/human epidermal growth factor receptor 2 (ER/PR/HER2) treated non-TNBC (SK-BR-3 and MCF-7) cells and blocked the ER/PR/HER2 activity. Wound-healing assays and Rho activation assays were employed to measure the effect of kaempferol and ER/PR/HER2 inhibitors on Rho activation and cell migration rates. A low dose of kaempferol (20 μmol/L) had a potent inhibitory effect on the migration and invasion of TNBC cells, but not on the migration of non-TNBC (SK-BR-3 and MCF-7) cells. The low dose of kaempferol downregulated the activations of RhoA and Rac1 in TNBC cells. Moreover, the low dose of kaempferol also inhibited the migration and RhoA activations of HER2-silence SK-BR-3 and ER/PR-silence MCF-7 cells. Overexpressed HER2 rescued the cell migration and RhoA and Rac1 activations of kaempferol-treated MDA-MB-231 cells. The low dose of kaempferol inhibits the migration and invasion of TNBC cells via blocking RhoA and Rac1 signaling pathway.

  8. Danish Breast Cancer Cooperative Group

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    Christiansen P

    2016-10-01

    Full Text Available Peer Christiansen,1 Bent Ejlertsen,2,3 Maj-Britt Jensen,3 Henning Mouridsen3 1Department of Surgery P, Breast Surgery Unit, Aarhus University Hospital/Randers Regional Hospital, Aarhus C, 2Department of Oncology, Rigshospitalet, Copenhagen University Hospital, 3DBCG-secretariat, Department 2501, Rigshospitalet, Copenhagen Ø, Denmark Aim of database: Danish Breast Cancer Cooperative Group (DBCG, with an associated database, was introduced as a nationwide multidisciplinary group in 1977 with the ultimate aim to improve the prognosis in breast cancer. Since then, the database has registered women diagnosed with primary invasive nonmetastatic breast cancer. The data reported from the departments to the database included details of the characteristics of the primary tumor, of surgery, radiotherapy, and systemic therapies, and of follow-up reported on specific forms from the departments in question. Descriptive data: From 1977 through 2014, ~110,000 patients are registered in the nationwide, clinical database. The completeness has gradually improved to more than 95%. DBCG has continuously prepared evidence-based guidelines on diagnosis and treatment of breast cancer and conducted quality control studies to ascertain the degree of adherence to the guidelines in the different departments. Conclusion: Utilizing data from the DBCG database, a long array of high-quality DBCG studies of various designs and scope, nationwide or in international collaboration, have contributed to the current updating of the guidelines, and have been an instrumental resource in the improvement of management and prognosis of breast cancer in Denmark. Thus, since the establishment of DBCG, the prognosis in breast cancer has continuously improved with a decrease in 5-year mortality from ~37% to 15%. Keywords: breast cancer, database, guidelines, quality control, research

  9. Breast Cancer Risk in American Women

    Science.gov (United States)

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

  10. Biomarker signatures of mitochondrial NDUFS3 in invasive breast carcinoma

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-09-09

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

  11. Human papilloma viruses (HPV and breast cancer.

    Directory of Open Access Journals (Sweden)

    James Sutherland Lawson

    2015-12-01

    Full Text Available Purpose: Human papillomaviruses (HPV may have a role in some breast cancers. The purpose of this study is to fill important gaps in the evidence. These gaps are: (i confirmation of the presence of high risk for cancer HPVs in breast cancers, (ii evidence of HPV infections in benign breast tissues prior to the development of HPV positive breast cancer in the same patients, (iii evidence that HPVs are biologically active and not harmless passengers in breast cancer.Methods: RNA-seq data from The Cancer Genome Atlas (TCGA was used to identify HPV RNA sequences in breast cancers. We also conducted a retrospective cohort study based on polymerase chain reaction (PCR analyses to identify HPVs in archival specimens from Australian women with benign breast biopsies who later developed breast cancer. To assess whether HPVs in breast cancer were biologically active, the expression of the oncogenic protein HPV E7 was assessed by immunohistochemistry (IHC.Results: Thirty (3.5% low risk and 20 (2.3% high risk HPV types were identified in 855 breast cancers from the TCGA data base. The high risk types were HPV 18 (48%, HPV 113 (24%, HPV 16 (10%, HPV 52 (10%. Data from the PCR cohort study, indicated that HPV type 18 was the most common type identified in breast cancer specimens (55% of