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Sample records for dedicated molecular breast

  1. Molecular Imaging in Breast Cancer: From Whole-Body PET/CT to Dedicated Breast PET

    Directory of Open Access Journals (Sweden)

    B. B. Koolen

    2012-01-01

    Full Text Available Positron emission tomography (PET, with or without integrated computed tomography (CT, using 18F-fluorodeoxyglucose (FDG is based on the principle of elevated glucose metabolism in malignant tumors, and its use in breast cancer patients is frequently being investigated. It has been shown useful for classification, staging, and response monitoring, both in primary and recurrent disease. However, because of the partial volume effect and limited resolution of most whole-body PET scanners, sensitivity for the visualization of small tumors is generally low. To improve the detection and quantification of primary breast tumors with FDG PET, several dedicated breast PET devices have been developed. In this nonsystematic review, we shortly summarize the value of whole-body PET/CT in breast cancer and provide an overview of currently available dedicated breast PETs.

  2. Performance characteristics of dedicated molecular breast imaging systems at low doses

    Energy Technology Data Exchange (ETDEWEB)

    Long, Zaiyang; Conners, Amy L.; Hunt, Katie N.; Hruska, Carrie B.; O’Connor, Michael K., E-mail: mkoconnor@mayo.edu [Department of Radiology, Mayo Clinic, Rochester, Minnesota 55905 (United States)

    2016-06-15

    Purpose: The purpose of this study was to compare the system performance characteristics and lesion detection capability of two molecular breast imaging (MBI) systems: a multicrystal sodium iodide (NaI)-based single-head system and a cadmium zinc telluride (CZT)-based dual-head system at low administered doses (150–300 MBq) of Tc-99m sestamibi. Methods: System performance characteristics including count sensitivity, uniformity, energy resolution, and spatial resolution were measured using standard NEMA methods, or a modified version thereof in cases where the standard NEMA protocol could not be applied. A contrast-detail phantom with 48 lesions at varying depths from the collimator surface was used to assess lesion contrast-to-noise-ratio (CNR) using background count densities comparable to those observed in patient studies performed with administered doses of 150 MBq Tc-99m sestamibi. Lesions with CNR >3 were deemed to be detectable. Thirty patients undergoing MBI examinations with administered doses of 150–300 MBq were scanned for an additional view on the pixelated NaI system. CNR was calculated for lesions observed on patient images. Background count densities of patient images were measured and compared between the two systems. Results: Over the central field of view, integral and differential uniformity were 6.1% and 4.2%, respectively, for the pixelated NaI system, and 3.8% and 2.7%, respectively, for the CZT system. Count sensitivity was 10.8 kcts/min/MBq for the NaI system and 32.9 kcts/min/MBq for the CZT system. Energy resolution was 13.5% on the pixelated NaI system and 4.5% on the CZT system. Spatial resolution (full-width at half-maximum) for the pixelated NaI detector was 4.2 mm at a distance of 1.2 cm from the collimator and 5.2 mm at 3.1 cm. Spatial resolution of a single CZT detector was 2.9 mm at a distance of 1.2 cm from the collimator and 4.7 mm at 3.1 cm. Effective spatial resolution obtained with dual-head CZT was below 4.7 mm throughout

  3. Automation and Preclinical Evaluation of a Dedicated Emission Mammotomography System for Fully 3-D Molecular Breast Imaging

    National Research Council Canada - National Science Library

    Cutler, Spencer J

    2007-01-01

    .... A retrospective study of 103 clinical MRI uncompressed breast scans was conducted to create surface renderings of the uncompressed breasts and analyze how to adapt existing acquisition orbits for varying breast shapes...

  4. Scintillator performance considerations for dedicated breast computed tomography

    Science.gov (United States)

    Vedantham, Srinivasan; Shi, Linxi; Karellas, Andrew

    2017-09-01

    Dedicated breast computed tomography (BCT) is an emerging clinical modality that can eliminate tissue superposition and has the potential for improved sensitivity and specificity for breast cancer detection and diagnosis. It is performed without physical compression of the breast. Most of the dedicated BCT systems use large-area detectors operating in cone-beam geometry and are referred to as cone-beam breast CT (CBBCT) systems. The large-area detectors in CBBCT systems are energy-integrating, indirect-type detectors employing a scintillator that converts x-ray photons to light, followed by detection of optical photons. A key consideration that determines the image quality achieved by such CBBCT systems is the choice of scintillator and its performance characteristics. In this work, a framework for analyzing the impact of the scintillator on CBBCT performance and its use for task-specific optimization of CBBCT imaging performance is described.

  5. Cone-beam micro computed tomography dedicated to the breast.

    Science.gov (United States)

    Sarno, Antonio; Mettivier, Giovanni; Di Lillo, Francesca; Cesarelli, Mario; Bifulco, Paolo; Russo, Paolo

    2016-12-01

    We developed a scanner for micro computed tomography dedicated to the breast (BµCT) with a high resolution flat-panel detector and a microfocus X-ray tube. We evaluated the system spatial resolution via the 3D modulation transfer function (MTF). In addition to conventional absorption-based X-ray imaging, such a prototype showed capabilities for propagation-based phase-contrast and related edge enhancement effects in 3D imaging. The system limiting spatial resolution is 6.2mm -1 (MTF at 10%) in the vertical direction and 3.8mm -1 in the radial direction, values which compare favorably with the spatial resolution reached by mini focus breast CT scanners of other groups. The BµCT scanner was able to detect both microcalcification clusters and masses in an anthropomorphic breast phantom at a dose comparable to that of two-view mammography. The use of a breast holder is proposed in order to have 1-2min long scan times without breast motion artifacts. Copyright © 2016 IPEM. Published by Elsevier Ltd. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Nicolas D. Prionas, MD, PhD

    2015-01-01

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

  7. Dedication

    OpenAIRE

    2013-01-01

    This work is dedicated, to my mom, Bridget, and my dad, (the late) Daniel Enwerem, who taught me to respect people but not fear them; and to those who are engaged or have been victims in the struggle for an egalitarian society in Nigeria.

  8. Performance evaluation of a high resolution dedicated breast PET scanner

    Energy Technology Data Exchange (ETDEWEB)

    García Hernández, Trinitat, E-mail: mtrinitat@eresa.com; Vicedo González, Aurora; Brualla González, Luis; Granero Cabañero, Domingo [Department of Medical Physics, ERESA, Hospital General Universitario, Valencia 46014 (Spain); Ferrer Rebolleda, Jose; Sánchez Jurado, Raúl; Puig Cozar Santiago, Maria del [Department of Nuclear Medicine, ERESA, Hospital General Universitario, Valencia 46014 (Spain); Roselló Ferrando, Joan [Department of Medical Physics, ERESA, Hospital General Universitario, Valencia 46014 (Spain); Department of Physiology, University of Valencia, Valencia 46010 (Spain)

    2016-05-15

    Purpose: Early stage breast cancers may not be visible on a whole-body PET scan. To overcome whole-body PET limitations, several dedicated breast positron emission tomography (DbPET) systems have emerged nowadays aiming to improve spatial resolution. In this work the authors evaluate the performance of a high resolution dedicated breast PET scanner (Mammi-PET, Oncovision). Methods: Global status, uniformity, sensitivity, energy, and spatial resolution were measured. Spheres of different sizes (2.5, 4, 5, and 6 mm diameter) and various 18 fluorodeoxyglucose ({sup 18}F-FDG) activity concentrations were randomly inserted in a gelatine breast phantom developed at our institution. Several lesion-to-background ratios (LBR) were simulated, 5:1, 10:1, 20:1, 30:1, and 50:1. Images were reconstructed using different voxel sizes. The ability of experienced reporters to detect spheres was tested as a function of acquisition time, LBR, sphere size, and matrix reconstruction voxel size. For comparison, phantoms were scanned in the DbPET camera and in a whole body PET (WB-PET). Two patients who just underwent WB-PET/CT exams were imaged with the DbPET system and the images were compared. Results: The measured absolute peak sensitivity was 2.0%. The energy resolution was 24.0% ± 1%. The integral and differential uniformity were 10% and 6% in the total field of view (FOV) and 9% and 5% in the central FOV, respectively. The measured spatial resolution was 2.0, 1.9, and 1.7 mm in the radial, tangential, and axial directions. The system exhibited very good detectability for spheres ≥4 mm and LBR ≥10 with a sphere detection of 100% when acquisition time was set >3 min/bed. For LBR = 5 and acquisition time of 7 min the detectability was 100% for spheres of 6 mm and 75% for spheres of 5, 4, and 2.5 mm. Lesion WB-PET detectability was only comparable to the DbPET camera for lesion sizes ≥5 mm when acquisition time was >3 min and LBR > 10. Conclusions: The DbPET has a good

  9. Design and evaluation of the MAMMI dedicated breast PET

    International Nuclear Information System (INIS)

    Moliner, L.; González, A. J.; Soriano, A.; Sánchez, F.; Correcher, C.; Orero, A.; Carles, M.; Vidal, L. F.; Barberá, J.; Caballero, L.; Seimetz, M.; Vázquez, C.; Benlloch, J. M.

    2012-01-01

    Purpose: A breast dedicated positron emission tomography (PET) scanner has been developed based on monolithic LYSO crystals coupled to position sensitive photomultiplier tubes (PSPMTs). In this study, we describe the design of the PET system and report on its performance evaluation. Methods: MAMMI is a breast PET scanner based on monolithic LYSO crystals. It consists of 12 compact modules with a transaxial field of view (FOV) of 170 mm in diameter and 40 mm axial FOV that translates to cover up to 170 mm. The patient lies down in a prone position that facilitates maximum breast elongation. Quantitative performance analysis of the calculated method for the attenuation correction specifically developed for MAMMI, and based on PET image segmentation, has also been conducted in this evaluation. In order to fully determine the MAMMI prototype's performance, we have adapted the measurements suggested for National Electrical Manufacturers Association (NEMA) NU 2-2007 and NU 4-2008 protocol tests, as they are defined for whole-body and small animal PET scanners, respectively. Results: Spatial resolutions of 1.6, 1.8, and 1.9 mm were measured in the axial, radial, and tangential directions, respectively. A scatter fraction of 20.8% was obtained and the maximum NEC was determined to be 25 kcps at 44 MBq. The average sensitivity of the system was observed to be 1% for an energy window of (250 keV–750 keV) and a maximum absolute sensitivity of 1.8% was measured at the FOV center. Conclusions: The overall performance of the MAMMI reported on this evaluation quantifies its ability to produce high quality PET images. Spatial resolution values below 3 mm were measured in most of the FOV. Only the radial component of spatial resolution exceeds the 3 mm at radial positions larger than 60 mm. This study emphasizes the need for standardized testing methodologies for dedicated breast PET systems similar to NEMA standards for whole-body and small animal PET scanners.

  10. Performance evaluation of a high resolution dedicated breast PET scanner

    International Nuclear Information System (INIS)

    García Hernández, Trinitat; Vicedo González, Aurora; Brualla González, Luis; Granero Cabañero, Domingo; Ferrer Rebolleda, Jose; Sánchez Jurado, Raúl; Puig Cozar Santiago, Maria del; Roselló Ferrando, Joan

    2016-01-01

    Purpose: Early stage breast cancers may not be visible on a whole-body PET scan. To overcome whole-body PET limitations, several dedicated breast positron emission tomography (DbPET) systems have emerged nowadays aiming to improve spatial resolution. In this work the authors evaluate the performance of a high resolution dedicated breast PET scanner (Mammi-PET, Oncovision). Methods: Global status, uniformity, sensitivity, energy, and spatial resolution were measured. Spheres of different sizes (2.5, 4, 5, and 6 mm diameter) and various 18 fluorodeoxyglucose ("1"8F-FDG) activity concentrations were randomly inserted in a gelatine breast phantom developed at our institution. Several lesion-to-background ratios (LBR) were simulated, 5:1, 10:1, 20:1, 30:1, and 50:1. Images were reconstructed using different voxel sizes. The ability of experienced reporters to detect spheres was tested as a function of acquisition time, LBR, sphere size, and matrix reconstruction voxel size. For comparison, phantoms were scanned in the DbPET camera and in a whole body PET (WB-PET). Two patients who just underwent WB-PET/CT exams were imaged with the DbPET system and the images were compared. Results: The measured absolute peak sensitivity was 2.0%. The energy resolution was 24.0% ± 1%. The integral and differential uniformity were 10% and 6% in the total field of view (FOV) and 9% and 5% in the central FOV, respectively. The measured spatial resolution was 2.0, 1.9, and 1.7 mm in the radial, tangential, and axial directions. The system exhibited very good detectability for spheres ≥4 mm and LBR ≥10 with a sphere detection of 100% when acquisition time was set >3 min/bed. For LBR = 5 and acquisition time of 7 min the detectability was 100% for spheres of 6 mm and 75% for spheres of 5, 4, and 2.5 mm. Lesion WB-PET detectability was only comparable to the DbPET camera for lesion sizes ≥5 mm when acquisition time was >3 min and LBR > 10. Conclusions: The DbPET has a good performance

  11. Reducing radiation dose to the female breast during conventional and dedicated breast computed tomography

    Science.gov (United States)

    Rupcich, Franco John

    The purpose of this study was to quantify the effectiveness of techniques intended to reduce dose to the breast during CT coronary angiography (CTCA) scans with respect to task-based image quality, and to evaluate the effectiveness of optimal energy weighting in improving contrast-to-noise ratio (CNR), and thus the potential for reducing breast dose, during energy-resolved dedicated breast CT. A database quantifying organ dose for several radiosensitive organs irradiated during CTCA, including the breast, was generated using Monte Carlo simulations. This database facilitates estimation of organ-specific dose deposited during CTCA protocols using arbitrary x-ray spectra or tube-current modulation schemes without the need to run Monte Carlo simulations. The database was used to estimate breast dose for simulated CT images acquired for a reference protocol and five protocols intended to reduce breast dose. For each protocol, the performance of two tasks (detection of signals with unknown locations) was compared over a range of breast dose levels using a task-based, signal-detectability metric: the estimator of the area under the exponential free-response relative operating characteristic curve, AFE. For large-diameter/medium-contrast signals, when maintaining equivalent AFE, the 80 kV partial, 80 kV, 120 kV partial, and 120 kV tube-current modulated protocols reduced breast dose by 85%, 81%, 18%, and 6%, respectively, while the shielded protocol increased breast dose by 68%. Results for the small-diameter/high-contrast signal followed similar trends, but with smaller magnitude of the percent changes in dose. The 80 kV protocols demonstrated the greatest reduction to breast dose, however, the subsequent increase in noise may be clinically unacceptable. Tube output for these protocols can be adjusted to achieve more desirable noise levels with lesser dose reduction. The improvement in CNR of optimally projection-based and image-based weighted images relative to photon

  12. Breast Imaging Utilizing Dedicated Gamma Camera and (99m)Tc-MIBI: Experience at the Tel Aviv Medical Center and Review of the Literature Breast Imaging.

    Science.gov (United States)

    Even-Sapir, Einat; Golan, Orit; Menes, Tehillah; Weinstein, Yuliana; Lerman, Hedva

    2016-07-01

    The scope of the current article is the clinical role of gamma cameras dedicated for breast imaging and (99m)Tc-MIBI tumor-seeking tracer, as both a screening modality among a healthy population and as a diagnostic modality in patients with breast cancer. Such cameras are now commercially available. The technology utilizing a camera composed of a NaI (Tl) detector is termed breast-specific gamma imaging. The technology of dual-headed camera composed of semiconductor cadmium zinc telluride detectors that directly converts gamma-ray energy into electronic signals is termed molecular breast imaging. Molecular breast imaging system has been installed at the Department of Nuclear medicine at the Tel Aviv Sourasky Medical Center, Tel Aviv in 2009. The article reviews the literature well as our own experience. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. A minimum spanning forest based classification method for dedicated breast CT images

    International Nuclear Information System (INIS)

    Pike, Robert; Sechopoulos, Ioannis; Fei, Baowei

    2015-01-01

    Purpose: To develop and test an automated algorithm to classify different types of tissue in dedicated breast CT images. Methods: Images of a single breast of five different patients were acquired with a dedicated breast CT clinical prototype. The breast CT images were processed by a multiscale bilateral filter to reduce noise while keeping edge information and were corrected to overcome cupping artifacts. As skin and glandular tissue have similar CT values on breast CT images, morphologic processing is used to identify the skin based on its position information. A support vector machine (SVM) is trained and the resulting model used to create a pixelwise classification map of fat and glandular tissue. By combining the results of the skin mask with the SVM results, the breast tissue is classified as skin, fat, and glandular tissue. This map is then used to identify markers for a minimum spanning forest that is grown to segment the image using spatial and intensity information. To evaluate the authors’ classification method, they use DICE overlap ratios to compare the results of the automated classification to those obtained by manual segmentation on five patient images. Results: Comparison between the automatic and the manual segmentation shows that the minimum spanning forest based classification method was able to successfully classify dedicated breast CT image with average DICE ratios of 96.9%, 89.8%, and 89.5% for fat, glandular, and skin tissue, respectively. Conclusions: A 2D minimum spanning forest based classification method was proposed and evaluated for classifying the fat, skin, and glandular tissue in dedicated breast CT images. The classification method can be used for dense breast tissue quantification, radiation dose assessment, and other applications in breast imaging

  14. ClearPEM: prototype PET device dedicated to breast imaging

    CERN Multimedia

    Joao Varela

    2009-01-01

    Clinical trials have begun in Portugal on a new breast imaging system (ClearPEM) using positron emission tomography (PET). The system, developed by a Portuguese consortium in collaboration with CERN and laboratories participating in the Crystal Clear collaboration, will detect even the smallest tumours and thus help avoid unnecessary biopsies.

  15. Local curvature analysis for classifying breast tumors: Preliminary analysis in dedicated breast CT

    International Nuclear Information System (INIS)

    Lee, Juhun; Nishikawa, Robert M.; Reiser, Ingrid; Boone, John M.; Lindfors, Karen K.

    2015-01-01

    Purpose: The purpose of this study is to measure the effectiveness of local curvature measures as novel image features for classifying breast tumors. Methods: A total of 119 breast lesions from 104 noncontrast dedicated breast computed tomography images of women were used in this study. Volumetric segmentation was done using a seed-based segmentation algorithm and then a triangulated surface was extracted from the resulting segmentation. Total, mean, and Gaussian curvatures were then computed. Normalized curvatures were used as classification features. In addition, traditional image features were also extracted and a forward feature selection scheme was used to select the optimal feature set. Logistic regression was used as a classifier and leave-one-out cross-validation was utilized to evaluate the classification performances of the features. The area under the receiver operating characteristic curve (AUC, area under curve) was used as a figure of merit. Results: Among curvature measures, the normalized total curvature (C_T) showed the best classification performance (AUC of 0.74), while the others showed no classification power individually. Five traditional image features (two shape, two margin, and one texture descriptors) were selected via the feature selection scheme and its resulting classifier achieved an AUC of 0.83. Among those five features, the radial gradient index (RGI), which is a margin descriptor, showed the best classification performance (AUC of 0.73). A classifier combining RGI and C_T yielded an AUC of 0.81, which showed similar performance (i.e., no statistically significant difference) to the classifier with the above five traditional image features. Additional comparisons in AUC values between classifiers using different combinations of traditional image features and C_T were conducted. The results showed that C_T was able to replace the other four image features for the classification task. Conclusions: The normalized curvature measure

  16. MR-Guided High-Intensity Focused Ultrasound Ablation of Breast Cancer with a Dedicated Breast Platform

    International Nuclear Information System (INIS)

    Merckel, Laura G.; Bartels, Lambertus W.; Köhler, Max O.; Bongard, H. J. G. Desirée van den; Deckers, Roel; Mali, Willem P. Th. M.; Binkert, Christoph A.; Moonen, Chrit T.; Gilhuijs, Kenneth G. A.; Bosch, Maurice A. A. J. van den

    2013-01-01

    Optimizing the treatment of breast cancer remains a major topic of interest. In current clinical practice, breast-conserving therapy is the standard of care for patients with localized breast cancer. Technological developments have fueled interest in less invasive breast cancer treatment. Magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) is a completely noninvasive ablation technique. Focused beams of ultrasound are used for ablation of the target lesion without disrupting the skin and subcutaneous tissues in the beam path. MRI is an excellent imaging method for tumor targeting, treatment monitoring, and evaluation of treatment results. The combination of HIFU and MR imaging offers an opportunity for image-guided ablation of breast cancer. Previous studies of MR-HIFU in breast cancer patients reported a limited efficacy, which hampered the clinical translation of this technique. These prior studies were performed without an MR-HIFU system specifically developed for breast cancer treatment. In this article, a novel and dedicated MR-HIFU breast platform is presented. This system has been designed for safe and effective MR-HIFU ablation of breast cancer. Furthermore, both clinical and technical challenges are discussed, which have to be solved before MR-HIFU ablation of breast cancer can be implemented in routine clinical practice.

  17. A dedicated breast-PET/CT scanner: Evaluation of basic performance characteristics.

    Science.gov (United States)

    Raylman, Raymond R; Van Kampen, Will; Stolin, Alexander V; Gong, Wenbo; Jaliparthi, Gangadhar; Martone, Peter F; Smith, Mark F; Sarment, David; Clinthorne, Neal H; Perna, Mark

    2018-04-01

    Application of advanced imaging techniques, such as PET and x ray CT, can potentially improve detection of breast cancer. Unfortunately, both modalities have challenges in the detection of some lesions. The combination of the two techniques, however, could potentially lead to an overall improvement in diagnostic breast imaging. The purpose of this investigation is to test the basic performance of a new dedicated breast-PET/CT. The PET component consists of a rotating pair of detectors. Its performance was evaluated using the NEMA NU4-2008 protocols. The CT component utilizes a pulsed x ray source and flat panel detector mounted on the same gantry as the PET scanner. Its performance was assessed using specialized phantoms. The radiation dose to a breast during CT imaging was explored by the measurement of free-in-air kerma and air kerma measured at the center of a 16 cm-diameter PMMA cylinder. Finally, the combined capabilities of the system were demonstrated by imaging of a micro-hot-rod phantom. Overall, performance of the PET component is comparable to many pre-clinical and other dedicated breast-PET scanners. Its spatial resolution is 2.2 mm, 5 mm from the center of the scanner using images created with the single-sliced-filtered-backprojection algorithm. Peak NECR is 24.6 kcps; peak sensitivity is 1.36%; the scatter fraction is 27%. Spatial resolution of the CT scanner is 1.1 lp/mm at 10% MTF. The free-in-air kerma is 2.33 mGy, while the PMMA-air kerma is 1.24 mGy. Finally, combined imaging of a micro-hot-rod phantom illustrated the potential utility of the dual-modality images produced by the system. The basic performance characteristics of a new dedicated breast-PET/CT scanner are good, demonstrating that its performance is similar to current dedicated PET and CT scanners. The potential value of this system is the capability to produce combined duality-modality images that could improve detection of breast disease. The next stage in development of this system

  18. TU-CD-207-11: Patient-Driven Automatic Exposure Control for Dedicated Breast CT

    International Nuclear Information System (INIS)

    Hernandez, A; Gazi, P; Seibert, J; Boone, J

    2015-01-01

    Purpose: To implement automatic exposure control (AEC) in dedicated breast CT (bCT) on a patient-specific basis using only the pre-scan scout views. Methods: Using a large cohort (N=153) of bCT data sets, the breast effective diameter (D) and width in orthogonal planes (Wa,Wb) were calculated from the reconstructed bCT image and pre-scan scout views, respectively. D, Wa, and Wb were measured at the breast center-of-mass (COM), making use of the known geometry of our bCT system. These data were then fit to a second-order polynomial “D=F(Wa,Wb)” in a least squares sense in order to provide a functional form for determining the breast diameter. The coefficient of determination (R 2 ) and mean percent error between the measured breast diameter and fit breast diameter were used to evaluate the overall robustness of the polynomial fit. Lastly, previously-reported bCT technique factors derived from Monte Carlo simulations were used to determine the tube current required for each breast diameter in order to match two-view mammographic dose levels. Results: F(Wa,Wb) provided fitted breast diameters in agreement with the measured breast diameters resulting in R 2 values ranging from 0.908 to 0.929 and mean percent errors ranging from 3.2% to 3.7%. For all 153 bCT data sets used in this study, the fitted breast diameters ranged from 7.9 cm to 15.7 cm corresponding to tube current values ranging from 0.6 mA to 4.9 mA in order to deliver the same dose as two-view mammography in a 50% glandular breast with a 80 kV x-ray beam and 16.6 second scan time. Conclusion: The present work provides a robust framework for AEC in dedicated bCT using only the width measurements derived from the two orthogonal pre-scan scout views. Future work will investigate how these automatically chosen exposure levels affect the quality of the reconstructed image

  19. TU-CD-207-11: Patient-Driven Automatic Exposure Control for Dedicated Breast CT

    Energy Technology Data Exchange (ETDEWEB)

    Hernandez, A; Gazi, P [Biomedical Engineering Graduate Group, University of California Davis, Davis, CA (United States); Department of Radiology, UC Davis Medical Center, Sacramento, CA (United States); Seibert, J; Boone, J [Department of Radiology, UC Davis Medical Center, Sacramento, CA (United States); Department of Biomedical Engineering, University of California Davis, Davis, CA (United States)

    2015-06-15

    Purpose: To implement automatic exposure control (AEC) in dedicated breast CT (bCT) on a patient-specific basis using only the pre-scan scout views. Methods: Using a large cohort (N=153) of bCT data sets, the breast effective diameter (D) and width in orthogonal planes (Wa,Wb) were calculated from the reconstructed bCT image and pre-scan scout views, respectively. D, Wa, and Wb were measured at the breast center-of-mass (COM), making use of the known geometry of our bCT system. These data were then fit to a second-order polynomial “D=F(Wa,Wb)” in a least squares sense in order to provide a functional form for determining the breast diameter. The coefficient of determination (R{sup 2}) and mean percent error between the measured breast diameter and fit breast diameter were used to evaluate the overall robustness of the polynomial fit. Lastly, previously-reported bCT technique factors derived from Monte Carlo simulations were used to determine the tube current required for each breast diameter in order to match two-view mammographic dose levels. Results: F(Wa,Wb) provided fitted breast diameters in agreement with the measured breast diameters resulting in R{sup 2} values ranging from 0.908 to 0.929 and mean percent errors ranging from 3.2% to 3.7%. For all 153 bCT data sets used in this study, the fitted breast diameters ranged from 7.9 cm to 15.7 cm corresponding to tube current values ranging from 0.6 mA to 4.9 mA in order to deliver the same dose as two-view mammography in a 50% glandular breast with a 80 kV x-ray beam and 16.6 second scan time. Conclusion: The present work provides a robust framework for AEC in dedicated bCT using only the width measurements derived from the two orthogonal pre-scan scout views. Future work will investigate how these automatically chosen exposure levels affect the quality of the reconstructed image.

  20. Molecular genetics of breast cancer

    International Nuclear Information System (INIS)

    Radice, P.; Pierotti, M. A.

    1997-01-01

    In the last two decades, molecular studies have enlightened the complexity of the genetic alterations that occur in breast cancer cells. To date, more than 40 different genes or loci have been found to be altered in breast carcinomas. Although some of these genes, as for example ERBB2, appear to be mutated in a high proportion of cases, their mechanism of action and their role in the different stages of cancer development are still poorly understood. More recently, two major determinants of the inherited predisposition to breast cancer, BRCA1 and BRCA2, have been isolated. As a consequence, it is now possible to screen families with a positive history of breast carcinomas for the identification of mutations carriers, in order to address these individuals into adequate programs of cancer surveillance and prevention

  1. BI-RADS categorisation of 2708 consecutive nonpalpable breast lesions in patients referred to a dedicated breast care unit

    International Nuclear Information System (INIS)

    Hamy, A.S.; Giacchetti, S.; Cuvier, C.; Perret, F.; Bonfils, S.; Charveriat, P.; Hocini, H.; Espie, M.; Albiter, M.; Bazelaire, C. de; Roquancourt, A. de

    2012-01-01

    To determine the malignancy rate of nonpalpable breast lesions, categorised according to the Breast Imaging Reporting and Data System (BI-RADS) classification in the setting of a Breast Care Unit. All nonpalpable breast lesions from consecutive patients referred to a dedicated Breast Care Unit were prospectively reviewed and classified into 5 BI-RADS assessment categories (0, 2, 3, 4, and 5). A total of 2708 lesions were diagnosed by mammography (71.6%), ultrasound (8.7%), mammography and ultrasound (19.5%), or MRI (0.2%). The distribution of the lesions by BI-RADS category was: 152 in category 0 (5.6%), 56 in category 2 (2.1%), 742 in category 3 (27.4%), 1523 in category 4 (56.2%) and 235 in category 5 (8.7%). Histology revealed 570 malignant lesions (32.9%), 152 high-risk lesions (8.8%), and 1010 benign lesions (58.3%). Malignancy was detected in 17 (2.3%) category 3 lesions, 364 (23.9%) category 4 lesions and 185 (78.7%) category 5 lesions. Median follow-up was 36.9 months. This pragmatic study reflects the assessment and management of breast impalpable abnormalities referred for care to a specialized Breast Unit. Multidisciplinary evaluation with BI-RADS classification accurately predicts malignancy, and reflects the quality of management. This assessment should be encouraged in community practice appraisal. (orig.)

  2. Detector design issues for compact nuclear emission cameras dedicated to breast imaging

    International Nuclear Information System (INIS)

    Levin, Craig S.

    2003-01-01

    Certain gamma ray and positron emitting radiotracers have shown great promise for use in the detection, diagnosis and staging of breast cancer. Unfortunately, standard nuclear emission cameras (SPECT, PET) found in the clinic are not practical for breast imaging of these emissions due to inadequate spatial and energy resolutions and sensitivity, large and awkward size, and relatively high cost per study. High spatial and energy resolutions and sensitivity are needed for good lesion detectability. Due to these limitations of standard cameras, there has been recent research into the development of small, compact nuclear emission imagers dedicated for close-proximity breast imaging. The small detector head size means a variety of exotic detectors or collimators may be implemented to improve spatial and energy resolution and sensitivity performances at a reasonable cost. In this paper, we will present some of the compact gamma ray and annihilation photon imaging detector designs that have been proposed and/or developed for dedicated breast imaging. We will review the physics and discuss the advantages and disadvantages of various detector configurations. Finally we will estimate the fundamental spatial resolution potential available with close-proximity nuclear emission imaging and discuss how one may approach those limits through proper detector design

  3. WE-FG-207A-00: Advances in Dedicated Breast CT

    International Nuclear Information System (INIS)

    2016-01-01

    Mammography-based screening has been a valuable imaging tool for the early detection of non-palpable lesions and has contributed to significant reduction in breast cancer associated mortality. However, the breast imaging community recognizes that mammography is not ideal, and in particular is inferior for women with dense breasts. Also, the 2-D projection of a 3-D organ results in tissue superposition contributing to false-positives. The sensitivity of mammography is breast-density dependent. Its sensitivity, especially in dense breasts, is low due to overlapping tissue and the fact that normal breast tissue, benign lesions and breast cancers all have similar “densities”, making lesion detection more difficult. We ideally need 3-D imaging for imaging the 3-D breast. MRI is 3-D, whole breast ultrasound is 3-D, digital breast tomosynthesis is called 3-D but is really “pseudo 3-D” due to poor resolution along the depth-direction. Also, and importantly, we need to be able to administer intravenous contrast agents for optimal imaging, similar to other organ systems in the body. Dedicated breast CT allows for 3-D imaging of the uncompressed breast. In current designs, the patient is positioned prone on the table and the breast is pendant through an aperture and the scan takes approximately 10 seconds [O’Connell et al., AJR 195: 496–509, 2010]. Almost on the heels of the invention of CT itself, work began on the development of dedicated breast CT. These early breast CT systems were used in clinical trials and the results from comparative performance evaluation of breast CT and mammography for 1625 subjects were reported in 1980 [Chang et al., Cancer 46: 939–46, 1980]. However, the technological limitations at that time stymied clinical translation for decades. Subsequent to the landmark article in 2001 [Boone et al., Radiology 221: 657–67, 2001] that demonstrated the potential feasibility in terms of radiation dose, multiple research groups are actively

  4. WE-FG-207A-01: Introduction to Dedicated Breast CT - Early Studies

    International Nuclear Information System (INIS)

    Vedantham, S.

    2016-01-01

    Mammography-based screening has been a valuable imaging tool for the early detection of non-palpable lesions and has contributed to significant reduction in breast cancer associated mortality. However, the breast imaging community recognizes that mammography is not ideal, and in particular is inferior for women with dense breasts. Also, the 2-D projection of a 3-D organ results in tissue superposition contributing to false-positives. The sensitivity of mammography is breast-density dependent. Its sensitivity, especially in dense breasts, is low due to overlapping tissue and the fact that normal breast tissue, benign lesions and breast cancers all have similar “densities”, making lesion detection more difficult. We ideally need 3-D imaging for imaging the 3-D breast. MRI is 3-D, whole breast ultrasound is 3-D, digital breast tomosynthesis is called 3-D but is really “pseudo 3-D” due to poor resolution along the depth-direction. Also, and importantly, we need to be able to administer intravenous contrast agents for optimal imaging, similar to other organ systems in the body. Dedicated breast CT allows for 3-D imaging of the uncompressed breast. In current designs, the patient is positioned prone on the table and the breast is pendant through an aperture and the scan takes approximately 10 seconds [O’Connell et al., AJR 195: 496–509, 2010]. Almost on the heels of the invention of CT itself, work began on the development of dedicated breast CT. These early breast CT systems were used in clinical trials and the results from comparative performance evaluation of breast CT and mammography for 1625 subjects were reported in 1980 [Chang et al., Cancer 46: 939–46, 1980]. However, the technological limitations at that time stymied clinical translation for decades. Subsequent to the landmark article in 2001 [Boone et al., Radiology 221: 657–67, 2001] that demonstrated the potential feasibility in terms of radiation dose, multiple research groups are actively

  5. WE-FG-207A-00: Advances in Dedicated Breast CT

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2016-06-15

    Mammography-based screening has been a valuable imaging tool for the early detection of non-palpable lesions and has contributed to significant reduction in breast cancer associated mortality. However, the breast imaging community recognizes that mammography is not ideal, and in particular is inferior for women with dense breasts. Also, the 2-D projection of a 3-D organ results in tissue superposition contributing to false-positives. The sensitivity of mammography is breast-density dependent. Its sensitivity, especially in dense breasts, is low due to overlapping tissue and the fact that normal breast tissue, benign lesions and breast cancers all have similar “densities”, making lesion detection more difficult. We ideally need 3-D imaging for imaging the 3-D breast. MRI is 3-D, whole breast ultrasound is 3-D, digital breast tomosynthesis is called 3-D but is really “pseudo 3-D” due to poor resolution along the depth-direction. Also, and importantly, we need to be able to administer intravenous contrast agents for optimal imaging, similar to other organ systems in the body. Dedicated breast CT allows for 3-D imaging of the uncompressed breast. In current designs, the patient is positioned prone on the table and the breast is pendant through an aperture and the scan takes approximately 10 seconds [O’Connell et al., AJR 195: 496–509, 2010]. Almost on the heels of the invention of CT itself, work began on the development of dedicated breast CT. These early breast CT systems were used in clinical trials and the results from comparative performance evaluation of breast CT and mammography for 1625 subjects were reported in 1980 [Chang et al., Cancer 46: 939–46, 1980]. However, the technological limitations at that time stymied clinical translation for decades. Subsequent to the landmark article in 2001 [Boone et al., Radiology 221: 657–67, 2001] that demonstrated the potential feasibility in terms of radiation dose, multiple research groups are actively

  6. WE-FG-207A-01: Introduction to Dedicated Breast CT - Early Studies

    Energy Technology Data Exchange (ETDEWEB)

    Vedantham, S. [University of Massachusetts Medical School (United States)

    2016-06-15

    Mammography-based screening has been a valuable imaging tool for the early detection of non-palpable lesions and has contributed to significant reduction in breast cancer associated mortality. However, the breast imaging community recognizes that mammography is not ideal, and in particular is inferior for women with dense breasts. Also, the 2-D projection of a 3-D organ results in tissue superposition contributing to false-positives. The sensitivity of mammography is breast-density dependent. Its sensitivity, especially in dense breasts, is low due to overlapping tissue and the fact that normal breast tissue, benign lesions and breast cancers all have similar “densities”, making lesion detection more difficult. We ideally need 3-D imaging for imaging the 3-D breast. MRI is 3-D, whole breast ultrasound is 3-D, digital breast tomosynthesis is called 3-D but is really “pseudo 3-D” due to poor resolution along the depth-direction. Also, and importantly, we need to be able to administer intravenous contrast agents for optimal imaging, similar to other organ systems in the body. Dedicated breast CT allows for 3-D imaging of the uncompressed breast. In current designs, the patient is positioned prone on the table and the breast is pendant through an aperture and the scan takes approximately 10 seconds [O’Connell et al., AJR 195: 496–509, 2010]. Almost on the heels of the invention of CT itself, work began on the development of dedicated breast CT. These early breast CT systems were used in clinical trials and the results from comparative performance evaluation of breast CT and mammography for 1625 subjects were reported in 1980 [Chang et al., Cancer 46: 939–46, 1980]. However, the technological limitations at that time stymied clinical translation for decades. Subsequent to the landmark article in 2001 [Boone et al., Radiology 221: 657–67, 2001] that demonstrated the potential feasibility in terms of radiation dose, multiple research groups are actively

  7. Molecular imaging of small animals with dedicated PET tomographs

    International Nuclear Information System (INIS)

    Chatziioannou, A.F.

    2002-01-01

    Biological discovery has moved at an accelerated pace in recent years, with a considerable focus on the transition from in vitro to in vivo models. As a result, there has been a significant increase in the need to adapt clinical imaging methods, as well as for novel imaging technologies for biological research. Positron emission tomography (PET) is a clinical imaging modality that permits the use of positron-labeled molecular imaging probes for non-invasive assays of biochemical processes. The imaging procedure can be repeatedly performed before and after interventions, thereby allowing each animal to be used as its own control. Positron-labeled compounds that target a range of molecular targets have been and continue to be synthesized, with examples of biological processes ranging from receptors and synthesis of transmitters in cell communication, to metabolic processes and gene expression. In animal research, PET has been used extensively in the past for studies of non-human primates and other larger animals. New detector technology has improved spatial resolution, and has made possible PET scanning for the study of the most important modern molecular biology model, the laboratory mouse. This paper presents the challenges facing PET technology as applied to small animal imaging, provides a historical overview of the development of small animal PET systems, and discusses the current state of the art in small animal PET technology. (orig.)

  8. Iterative reconstruction using a Monte Carlo based system transfer matrix for dedicated breast positron emission tomography

    Energy Technology Data Exchange (ETDEWEB)

    Saha, Krishnendu [Ohio Medical Physics Consulting, Dublin, Ohio 43017 (United States); Straus, Kenneth J.; Glick, Stephen J. [Department of Radiology, University of Massachusetts Medical School, Worcester, Massachusetts 01655 (United States); Chen, Yu. [Department of Radiation Oncology, Columbia University, New York, New York 10032 (United States)

    2014-08-28

    To maximize sensitivity, it is desirable that ring Positron Emission Tomography (PET) systems dedicated for imaging the breast have a small bore. Unfortunately, due to parallax error this causes substantial degradation in spatial resolution for objects near the periphery of the breast. In this work, a framework for computing and incorporating an accurate system matrix into iterative reconstruction is presented in an effort to reduce spatial resolution degradation towards the periphery of the breast. The GATE Monte Carlo Simulation software was utilized to accurately model the system matrix for a breast PET system. A strategy for increasing the count statistics in the system matrix computation and for reducing the system element storage space was used by calculating only a subset of matrix elements and then estimating the rest of the elements by using the geometric symmetry of the cylindrical scanner. To implement this strategy, polar voxel basis functions were used to represent the object, resulting in a block-circulant system matrix. Simulation studies using a breast PET scanner model with ring geometry demonstrated improved contrast at 45% reduced noise level and 1.5 to 3 times resolution performance improvement when compared to MLEM reconstruction using a simple line-integral model. The GATE based system matrix reconstruction technique promises to improve resolution and noise performance and reduce image distortion at FOV periphery compared to line-integral based system matrix reconstruction.

  9. Personalized estimates of radiation dose from dedicated breast CT in a diagnostic population and comparison with diagnostic mammography

    International Nuclear Information System (INIS)

    Vedantham, Srinivasan; Shi, Linxi; Karellas, Andrew; O'Connell, Avice M; Conover, David L

    2013-01-01

    This study retrospectively analyzed the mean glandular dose (MGD) to 133 breasts from 132 subjects, all women, who participated in a clinical trial evaluating dedicated breast CT in a diagnostic population. The clinical trial was conducted in adherence to a protocol approved by institutional review boards and the study participants provided written informed consent. Individual estimates of MGD to each breast from dedicated breast CT was obtained by combining x-ray beam characteristics with estimates of breast dimensions and fibroglandular fraction from volumetric breast CT images, and using normalized glandular dose coefficients. For each study participant and for the breast corresponding to that imaged with breast CT, an estimate of the MGD from diagnostic mammography (including supplemental views) was obtained from the DICOM image headers for comparison. This estimate uses normalized glandular dose coefficients corresponding to a breast with 50% fibroglandular weight fraction. The median fibroglandular weight fraction for the study cohort determined from volumetric breast CT images was 15%. Hence, the MGD from diagnostic mammography was corrected to be representative of the study cohort. Individualized estimates of MGD from breast CT ranged from 5.7 to 27.8 mGy. Corresponding to the breasts imaged with breast CT, the MGD from diagnostic mammography ranged from 2.6 to 31.6 mGy. The mean (± inter-breast SD) and the median MGD (mGy) from dedicated breast CT exam were 13.9 ± 4.6 and 12.6, respectively. For the corresponding breasts, the mean (± inter-breast SD) and the median MGD (mGy) from diagnostic mammography were 12.4 ± 6.3 and 11.1, respectively. Statistical analysis indicated that at the 0.05 level, the distributions of MGD from dedicated breast CT and diagnostic mammography were significantly different (Wilcoxon signed ranks test, p = 0.007). While the interquartile range and the range (maximum–minimum) of MGD from dedicated breast CT was lower than

  10. Dedicated breast CT: radiation dose for circle-plus-line trajectory

    International Nuclear Information System (INIS)

    Vedantham, Srinivasan; Shi, Linxi; Karellas, Andrew; Noo, Frederic

    2012-01-01

    Purpose: Dedicated breast CT prototypes used in clinical investigations utilize single circular source trajectory and cone-beam geometry with flat-panel detectors that do not satisfy data-sufficiency conditions and could lead to cone beam artifacts. Hence, this work investigated the glandular dose characteristics of a circle-plus-line trajectory that fulfills data-sufficiency conditions for image reconstruction in dedicated breast CT. Methods: Monte Carlo-based computer simulations were performed using the GEANT4 toolkit and was validated with previously reported normalized glandular dose coefficients for one prototype breast CT system. Upon validation, Monte Carlo simulations were performed to determine the normalized glandular dose coefficients as a function of x-ray source position along the line scan. The source-to-axis of rotation distance and the source-to-detector distance were maintained constant at 65 and 100 cm, respectively, in all simulations. The ratio of the normalized glandular dose coefficient at each source position along the line scan to that for the circular scan, defined as relative normalized glandular dose coefficient (RD g N), was studied by varying the diameter of the breast at the chest wall, chest-wall to nipple distance, skin thickness, x-ray beam energy, and glandular fraction of the breast. Results: The RD g N metric when stated as a function of source position along the line scan, relative to the maximum length of line scan needed for data sufficiency, was found to be minimally dependent on breast diameter, chest-wall to nipple distance, skin thickness, glandular fraction, and x-ray photon energy. This observation facilitates easy estimation of the average glandular dose of the line scan. Polynomial fit equations for computing the RD g N and hence the average glandular dose are provided. Conclusions: For a breast CT system that acquires 300-500 projections over 2π for the circular scan, the addition of a line trajectory with equal

  11. X-ray scatter correction method for dedicated breast computed tomography: improvements and initial patient testing

    International Nuclear Information System (INIS)

    Ramamurthy, Senthil; D’Orsi, Carl J; Sechopoulos, Ioannis

    2016-01-01

    A previously proposed x-ray scatter correction method for dedicated breast computed tomography was further developed and implemented so as to allow for initial patient testing. The method involves the acquisition of a complete second set of breast CT projections covering 360° with a perforated tungsten plate in the path of the x-ray beam. To make patient testing feasible, a wirelessly controlled electronic positioner for the tungsten plate was designed and added to a breast CT system. Other improvements to the algorithm were implemented, including automated exclusion of non-valid primary estimate points and the use of a different approximation method to estimate the full scatter signal. To evaluate the effectiveness of the algorithm, evaluation of the resulting image quality was performed with a breast phantom and with nine patient images. The improvements in the algorithm resulted in the avoidance of introduction of artifacts, especially at the object borders, which was an issue in the previous implementation in some cases. Both contrast, in terms of signal difference and signal difference-to-noise ratio were improved with the proposed method, as opposed to with the correction algorithm incorporated in the system, which does not recover contrast. Patient image evaluation also showed enhanced contrast, better cupping correction, and more consistent voxel values for the different tissues. The algorithm also reduces artifacts present in reconstructions of non-regularly shaped breasts. With the implemented hardware and software improvements, the proposed method can be reliably used during patient breast CT imaging, resulting in improvement of image quality, no introduction of artifacts, and in some cases reduction of artifacts already present. The impact of the algorithm on actual clinical performance for detection, diagnosis and other clinical tasks in breast imaging remains to be evaluated. (paper)

  12. Library based x-ray scatter correction for dedicated cone beam breast CT

    International Nuclear Information System (INIS)

    Shi, Linxi; Zhu, Lei; Vedantham, Srinivasan; Karellas, Andrew

    2016-01-01

    Purpose: The image quality of dedicated cone beam breast CT (CBBCT) is limited by substantial scatter contamination, resulting in cupping artifacts and contrast-loss in reconstructed images. Such effects obscure the visibility of soft-tissue lesions and calcifications, which hinders breast cancer detection and diagnosis. In this work, we propose a library-based software approach to suppress scatter on CBBCT images with high efficiency, accuracy, and reliability. Methods: The authors precompute a scatter library on simplified breast models with different sizes using the GEANT4-based Monte Carlo (MC) toolkit. The breast is approximated as a semiellipsoid with homogeneous glandular/adipose tissue mixture. For scatter correction on real clinical data, the authors estimate the breast size from a first-pass breast CT reconstruction and then select the corresponding scatter distribution from the library. The selected scatter distribution from simplified breast models is spatially translated to match the projection data from the clinical scan and is subtracted from the measured projection for effective scatter correction. The method performance was evaluated using 15 sets of patient data, with a wide range of breast sizes representing about 95% of general population. Spatial nonuniformity (SNU) and contrast to signal deviation ratio (CDR) were used as metrics for evaluation. Results: Since the time-consuming MC simulation for library generation is precomputed, the authors’ method efficiently corrects for scatter with minimal processing time. Furthermore, the authors find that a scatter library on a simple breast model with only one input parameter, i.e., the breast diameter, sufficiently guarantees improvements in SNU and CDR. For the 15 clinical datasets, the authors’ method reduces the average SNU from 7.14% to 2.47% in coronal views and from 10.14% to 3.02% in sagittal views. On average, the CDR is improved by a factor of 1.49 in coronal views and 2.12 in sagittal

  13. Library based x-ray scatter correction for dedicated cone beam breast CT

    Energy Technology Data Exchange (ETDEWEB)

    Shi, Linxi; Zhu, Lei, E-mail: leizhu@gatech.edu [Nuclear and Radiological Engineering and Medical Physics Programs, The George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, Georgia 30332 (United States); Vedantham, Srinivasan; Karellas, Andrew [Department of Radiology, University of Massachusetts Medical School, Worcester, Massachusetts 01655 (United States)

    2016-08-15

    Purpose: The image quality of dedicated cone beam breast CT (CBBCT) is limited by substantial scatter contamination, resulting in cupping artifacts and contrast-loss in reconstructed images. Such effects obscure the visibility of soft-tissue lesions and calcifications, which hinders breast cancer detection and diagnosis. In this work, we propose a library-based software approach to suppress scatter on CBBCT images with high efficiency, accuracy, and reliability. Methods: The authors precompute a scatter library on simplified breast models with different sizes using the GEANT4-based Monte Carlo (MC) toolkit. The breast is approximated as a semiellipsoid with homogeneous glandular/adipose tissue mixture. For scatter correction on real clinical data, the authors estimate the breast size from a first-pass breast CT reconstruction and then select the corresponding scatter distribution from the library. The selected scatter distribution from simplified breast models is spatially translated to match the projection data from the clinical scan and is subtracted from the measured projection for effective scatter correction. The method performance was evaluated using 15 sets of patient data, with a wide range of breast sizes representing about 95% of general population. Spatial nonuniformity (SNU) and contrast to signal deviation ratio (CDR) were used as metrics for evaluation. Results: Since the time-consuming MC simulation for library generation is precomputed, the authors’ method efficiently corrects for scatter with minimal processing time. Furthermore, the authors find that a scatter library on a simple breast model with only one input parameter, i.e., the breast diameter, sufficiently guarantees improvements in SNU and CDR. For the 15 clinical datasets, the authors’ method reduces the average SNU from 7.14% to 2.47% in coronal views and from 10.14% to 3.02% in sagittal views. On average, the CDR is improved by a factor of 1.49 in coronal views and 2.12 in sagittal

  14. Clear-PEM: A dedicated PET camera for improved breast cancer detection

    International Nuclear Information System (INIS)

    Abreu, M. C.; Almeida, P.; Balau, F.; Ferreira, N. C.; Fetal, S.; Fraga, F.; Martins, M.; Matela, N.; Moura, R.; Ortigao, C.; Peralta, L.; Rato, P.; Ribeiro, R.; Rodrigues, P.; Santos, A. I.; Trindade, A.; Varela, J.

    2005-01-01

    Positron emission mammography (PEM) can offer a non-invasive method for the diagnosis of breast cancer. Metabolic images from PEM using 18 F-fluoro-deoxy-glucose, contain unique information not available from conventional morphologic imaging techniques like X-ray radiography. In this work, the concept of Clear-PEM, the system presently developed in the frame of the Crystal Clear Collaboration at CERN, is described. Clear-PEM will be a dedicated scanner, offering better perspectives in terms of position resolution and detection sensitivity. (authors)

  15. Clear-PEM: A PET imaging system dedicated to breast cancer diagnostics

    CERN Document Server

    Abreu, M C; Albuquerque, E; Almeida, F G; Almeida, P; Amaral, P; Auffray, Etiennette; Bento, P; Bruyndonckx, P; Bugalho, R; Carriço, B; Cordeiro, H; Ferreira, M; Ferreira, N C; Gonçalves, F; Lecoq, Paul; Leong, C; Lopes, F; Lousã, P; Luyten, J; Martins, M V; Matela, N; Rato-Mendes, P; Moura, R; Nobre, J; Oliveira, N; Ortigão, C; Peralta, L; Rego, J; Ribeiro, R; Rodrigues, P; Santos, A I; Silva, J C; Silva, M M; Tavernier, Stefaan; Teixeira, I C; Texeira, J P; Trindade, A; Trummer, Julia; Varela, J

    2007-01-01

    The Clear-PEM scanner for positron emission mammography under development is described. The detector is based on pixelized LYSO crystals optically coupled to avalanche photodiodes and readout by a fast low-noise electronic system. A dedicated digital trigger (TGR) and data acquisition (DAQ) system is used for on-line selection of coincidence events with high efficiency, large bandwidth and small dead-time. A specialized gantry allows to perform exams of the breast and of the axilla. In this paper we present results of the measurement of detector modules that integrate the system under construction as well as the imaging performance estimated from Monte Carlo simulated data.

  16. TU-EF-207-05: Dedicated Cone-beam Breast CT

    Energy Technology Data Exchange (ETDEWEB)

    Vedantham, S. [Univ. of Massachusetts Medical School (United States)

    2015-06-15

    mode due to lower photon fluence per projection. This may require fast-frame acquisition and symmetric or asymmetric pixel binning in some systems. Recent studies investigated the performance of increased conversion layer thickness for contrast-enhanced imaging of the breast in dual-energy acquisition mode. In other direct conversion detectors operating in the avalanche mode, sensitivities close to the single photon response are also explored for mammography and breast tomosynthesis. The potential advantages and challenges of this approach are described. Dedicated breast CT brings x-ray imaging of the breast to true tomographic 3D imaging. It can eliminate the tissue superposition problem and does not require physical compression of the breast. Using cone beam geometry and a flat-panel detector, several hundred projections are acquired and reconstructed to near isotropic voxels. Multiplanar reconstruction facilitates viewing the breast volume in any desired orientation. Ongoing clinical studies, the current state-of-the art, and research to advance the technology are described. Learning Objectives: To understand the ongoing developments in x-ray imaging of the breast To understand the approaches and applications of spectral mammography To understand the potential advantages of distributed x-ray source arrays for digital breast tomosynthesis To understand the ongoing developments in detector technology for digital mammography and breast tomosynthesis To understand the current state-of-the-art for dedicated cone-beam breast CT and research to advance the technology. Research collaboration with Koning Corporation.

  17. TU-EF-207-05: Dedicated Cone-beam Breast CT

    International Nuclear Information System (INIS)

    Vedantham, S.

    2015-01-01

    mode due to lower photon fluence per projection. This may require fast-frame acquisition and symmetric or asymmetric pixel binning in some systems. Recent studies investigated the performance of increased conversion layer thickness for contrast-enhanced imaging of the breast in dual-energy acquisition mode. In other direct conversion detectors operating in the avalanche mode, sensitivities close to the single photon response are also explored for mammography and breast tomosynthesis. The potential advantages and challenges of this approach are described. Dedicated breast CT brings x-ray imaging of the breast to true tomographic 3D imaging. It can eliminate the tissue superposition problem and does not require physical compression of the breast. Using cone beam geometry and a flat-panel detector, several hundred projections are acquired and reconstructed to near isotropic voxels. Multiplanar reconstruction facilitates viewing the breast volume in any desired orientation. Ongoing clinical studies, the current state-of-the art, and research to advance the technology are described. Learning Objectives: To understand the ongoing developments in x-ray imaging of the breast To understand the approaches and applications of spectral mammography To understand the potential advantages of distributed x-ray source arrays for digital breast tomosynthesis To understand the ongoing developments in detector technology for digital mammography and breast tomosynthesis To understand the current state-of-the-art for dedicated cone-beam breast CT and research to advance the technology. Research collaboration with Koning Corporation

  18. Scaling-law for the energy dependence of anatomic power spectrum in dedicated breast CT

    Energy Technology Data Exchange (ETDEWEB)

    Vedantham, Srinivasan; Shi, Linxi; Glick, Stephen J.; Karellas, Andrew [Department of Radiology, University of Massachusetts Medical School, Worcester, Massachusetts 01655 (United States)

    2013-01-15

    Purpose: To determine the x-ray photon energy dependence of the anatomic power spectrum of the breast when imaged with dedicated breast computed tomography (CT). Methods: A theoretical framework for scaling the empirically determined anatomic power spectrum at one x-ray photon energy to that at any given x-ray photon energy when imaged with dedicated breast CT was developed. Theory predicted that when the anatomic power spectrum is fitted with a power curve of the form k f{sup -{beta}}, where k and {beta} are fit coefficients and f is spatial frequency, the exponent {beta} would be independent of x-ray photon energy (E), and the amplitude k scales with the square of the difference in energy-dependent linear attenuation coefficients of fibroglandular and adipose tissues. Twenty mastectomy specimens based numerical phantoms that were previously imaged with a benchtop flat-panel cone-beam CT system were converted to 3D distribution of glandular weight fraction (f{sub g}) and were used to verify the theoretical findings. The 3D power spectrum was computed in terms of f{sub g} and after converting to linear attenuation coefficients at monoenergetic x-ray photon energies of 20-80 keV in 5 keV intervals. The 1D power spectra along the axes were extracted and fitted with a power curve of the form k f{sup -{beta}}. The energy dependence of k and {beta} were analyzed. Results: For the 20 mastectomy specimen based numerical phantoms used in the study, the exponent {beta} was found to be in the range of 2.34-2.42, depending on the axis of measurement. Numerical simulations agreed with the theoretical predictions that for a power-law anatomic spectrum of the form k f{sup -{beta}}, {beta} was independent of E and k(E) =k{sub 1}[{mu}{sub g}(E) -{mu}{sub a}(E)]{sup 2}, where k{sub 1} is a constant, and {mu}{sub g}(E) and {mu}{sub a}(E) represent the energy-dependent linear attenuation coefficients of fibroglandular and adipose tissues, respectively. Conclusions: Numerical

  19. Molecular pathology of breast apocrine carcinomas

    DEFF Research Database (Denmark)

    Celis, J.E.; Gromova, I.; Gromov, P.

    2006-01-01

    .5% of all invasive breast cancers according to the Danish Breast Cancer Cooperative Group Registry, and despite the fact that they are morphologically distinct from other breast lesions, there are at present no standard molecular criteria available for their diagnosis. In addition, the relationship between...

  20. SU-F-I-01: Normalized Mean Glandular Dose Values for Dedicated Breast CT Using Realistic Breast-Shaped Phantoms

    Energy Technology Data Exchange (ETDEWEB)

    Hernandez, A [Department of Radiology, Biomedical Engineering Graduate Group, University of California Davis, Sacramento, CA (United States); Boone, J [Departments of Radiology and Biomedical Engineering, Biomedical Engeering Graduate Group, University of California Davis, Sacramento, CA (United States)

    2016-06-15

    Purpose: To estimate normalized mean glandular dose values for dedicated breast CT (DgN-CT) using breast CT-derived phantoms and compare to estimations using cylindrical phantoms. Methods: Segmented breast CT (bCT) volume data sets (N=219) were used to measure effective diameter profiles and were grouped into quintiles by volume. The profiles were averaged within each quintile to represent the range of breast sizes found clinically. These profiles were then used to generate five voxelized computational phantoms (V1, V2, V3, V4, V5 for the small to large phantom sizes, respectively), and loaded into the MCNP6 lattice geometry to simulate normalized mean glandular dose coefficients (DgN-CT) using the system specifications of the Doheny-prototype bCT scanner in our laboratory. The DgN-CT coefficients derived from the bCT-derived breast-shaped phantoms were compared to those generated using a simpler cylindrical phantom using a constant volume, and the following constraints: (1) Length=1.5*radius; (2) radius determined at chest wall (Rcw), and (3) radius determined at the phantom center-of-mass (Rcm). Results: The change in Dg-NCT coefficients averaged across all phantom sizes, was - 0.5%, 19.8%, and 1.3%, for constraints 1–3, respectively. This suggests that the cylindrical assumption is a good approximation if the radius is taken at the breast center-of-mass, but using the radius at the chest wall results in an underestimation of the glandular dose. Conclusion: The DgN-CT coefficients for bCT-derived phantoms were compared against the assumption of a cylindrical phantom and proved to be essentially equivalent when the cylinder radius was set to r=1.5/L or Rcm. While this suggests that for dosimetry applications a patient’s breast can be approximated as a cylinder (if the correct radius is applied), this assumes a homogenous composition of breast tissue and the results may be different if the realistic heterogeneous distribution of glandular tissue is considered

  1. TU-F-18C-07: Hardware Advances for MTF Improvement in Dedicated Breast CT

    International Nuclear Information System (INIS)

    Gazi, P; Burkett, G; Yang, K; Boone, J

    2014-01-01

    Purpose: In this study, we have designed and implemented a prototype dedicated breast CT system (bCT) to improve the spatial resolution characteristics, in order to improve detection of micro-calcifications. Methods: A 10.8 kW water-cooled, tungsten anode x-ray tube, running up to 240 mA at 60 kV, coupled with an x-ray generator specifically designed for this application, and 0.3 mm of added copper filter was used to generate x-ray pulses. A CsI CMOS flat panel detector with a pixel pitch of 0.075 mm in native binning mode was used. The system geometry was designed in a way to achieve an FOV on par with similar bCT prototypes, resulting in a magnification factor of 1.39. A 0.013 mm tungsten wire was used to generate point spread functions. Multiple scans were performed with different numbers of projections, different reconstruction kernel sizes and different reconstruction filters to study the effects of each parameter on MTF. The resulting MTFs were then evaluated quantitatively using the generated PFSs. Duplicate scans with the same parameters were performed on two other dedicated breast CT systems to compare the performance of the new prototype. Results: The results of the MTF experiments demonstrate a significant improvement in the spatial resolution characteristics. In the new prototype, using the pulsed x-ray source results in a restoration of the azimuthal MTF degradation, due to motion blurring previously seen in other bCT systems. Moreover, employing the higher resolution x-ray detector considerably improves the MTF. The MTF at 10% of the new system is at 3.5 1/mm, a factor of 4.36 greater than an earlier bCT scanner. Conclusion: The MTF analysis of the new prototype bCT shows that using the new hardware and control results in a significant improvement in visualization of finer detail. This suggests that the visualization of micro-calcifications will be significantly improved

  2. Genetics and molecular biology of breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    King, M.C. [California Univ., Berkeley, CA (United States); Lippman, M. [Georgetown Univ. Medical Center, Washington, DC (United States)] [comps.

    1992-12-31

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

  3. Time of flight measurements based on FPGA using a breast dedicated PET

    International Nuclear Information System (INIS)

    Aguilar, A; García-Olcina, R; Martos, J; Soret, J; Torres, J; Benlloch, J M; González, A J; Sánchez, F

    2014-01-01

    In this work the implementation of a Time-to-Digital Converter (TDC) using a Nutt delay line FPGA-based and applied on a Positron Emission Tomography (PET) device is going to be presented in order to check the system's suitability for Time of Flight (TOF) measurements. In recent years, FPGAs have shown great advantages for precise time measurements in PET. The architecture employed for these measurements is described in detail. The system developed was tested on a dedicated breast PET prototype, composed of LYSO crystals and Positive Sensitive Photomultipliers (PSPMTs). Two distinct experiments were carried out for this purpose. In the first test, system linearity was evaluated in order to calibrate the time measurements, providing a linearity error of less than 2% and an average time resolution of 1.4 ns FWHM. The second set of measurements tested system resolution, resulting in a FWHM as good as 1.35 ns. The results suggest that the coincidence window for the current PET can be reduced in order to minimize the random events and thus, achieve better image quality

  4. Development of a circular shape Si-PM-based detector ring for breast-dedicated PET system

    Science.gov (United States)

    Nakanishi, Kouhei; Yamamoto, Seiichi; Watabe, Hiroshi; Abe, Shinji; Fujita, Naotoshi; Kato, Katsuhiko

    2018-02-01

    In clinical situations, various breast-dedicated positron emission tomography (PET) systems have been used. However, clinical breast-dedicated PET systems have polygonal detector ring. Polygonal detector ring sometimes causes image artifact, so complicated reconstruction algorithm is needed to reduce artifact. Consequently, we developed a circular detector ring for breast-dedicated PET to obtain images without artifact using a simple reconstruction algorithm. We used Lu1.9Gd0.1SiO5 (LGSO) scintillator block which was made of 1.5 x 1.9 x 15 mm pixels that were arranged in an 8 x 24 matrix. As photodetectors, we used silicon photomultiplier (Si-PM) arrays whose channel size was 3 x 3 mm. A detector unit was composed of four scintillator blocks, 16 Si-PM arrays and a light guide. The developed detector unit had angled configuration since the light guide was bending. A detector unit had three gaps with an angle of 5.625° between scintillator blocks. With these configurations, we could arrange 64 scintillator blocks in nearly circular shape (regular 64-sided polygon) using 16 detector units. The use of the smaller number of detector units could reduce the size of the front-end electronics circuits. The inner diameter of the developed detector ring was 260 mm. This size was similar to those of brain PET systems, so our breast-dedicated PET detector ring can measure not only breast but also brain. Measured radial, tangential and axial spatial resolution of the detector ring reconstructed by the filtered back-projection (FBP) algorithm were 2.1 mm FWHM, 2.0 mm FWHM and 1.7 mm FWHM at center of field of view (FOV), respectively. The sensitivity was 2.0% at center of the axial FOV. With the developed detector ring, we could obtain high resolution image of the breast phantom and the brain phantom. We conclude that our developed Si-PM-based detector ring is promising for a high resolution breast-dedicated PET system that can also be used for brain PET system.

  5. First clinical experience with a dedicated MRI-guided high-intensity focused ultrasound system for breast cancer ablation

    Energy Technology Data Exchange (ETDEWEB)

    Merckel, Laura G.; Knuttel, Floor M.; Peters, Nicky H.G.M.; Mali, Willem P.T.M.; Bosch, Maurice A.A.J. van den [University Medical Center Utrecht, Department of Radiology, HP E 01.132, Utrecht (Netherlands); Deckers, Roel; Moonen, Chrit T.W.; Bartels, Lambertus W. [University Medical Center Utrecht, Image Sciences Institute, Utrecht (Netherlands); Dalen, Thijs van [Diakonessenhuis Utrecht, Department of Surgery, Utrecht (Netherlands); Schubert, Gerald [Philips Healthcare, Best (Netherlands); Weits, Teun [Diakonessenhuis Utrecht, Department of Radiology, Utrecht (Netherlands); Diest, Paul J. van [University Medical Center Utrecht, Department of Pathology, Utrecht (Netherlands); Vaessen, Paul H.H.B. [University Medical Center Utrecht, Department of Anesthesiology, Utrecht (Netherlands); Gorp, Joost M.H.H. van [Diakonessenhuis Utrecht, Department of Pathology, Utrecht (Netherlands)

    2016-11-15

    To assess the safety and feasibility of MRI-guided high-intensity focused ultrasound (MR-HIFU) ablation in breast cancer patients using a dedicated breast platform. Patients with early-stage invasive breast cancer underwent partial tumour ablation prior to surgical resection. MR-HIFU ablation was performed using proton resonance frequency shift MR thermometry and an MR-HIFU system specifically designed for breast tumour ablation. The presence and extent of tumour necrosis was assessed by histopathological analysis of the surgical specimen. Pearson correlation coefficients were calculated to assess the relationship between sonication parameters, temperature increase and size of tumour necrosis at histopathology. Ten female patients underwent MR-HIFU treatment. No skin redness or burns were observed in any of the patients. No correlation was found between the applied energy and the temperature increase. In six patients, tumour necrosis was observed with a maximum diameter of 3-11 mm. In these patients, the number of targeted locations was equal to the number of areas with tumour necrosis. A good correlation was found between the applied energy and the size of tumour necrosis at histopathology (Pearson = 0.76, p = 0.002). Our results show that MR-HIFU ablation with the dedicated breast system is safe and results in histopathologically proven tumour necrosis. (orig.)

  6. WE-FG-207A-05: Dedicated Breast CT as a Diagnostic Imaging Tool: Physics and Clinical Feasibility

    International Nuclear Information System (INIS)

    Karellas, A.

    2016-01-01

    Mammography-based screening has been a valuable imaging tool for the early detection of non-palpable lesions and has contributed to significant reduction in breast cancer associated mortality. However, the breast imaging community recognizes that mammography is not ideal, and in particular is inferior for women with dense breasts. Also, the 2-D projection of a 3-D organ results in tissue superposition contributing to false-positives. The sensitivity of mammography is breast-density dependent. Its sensitivity, especially in dense breasts, is low due to overlapping tissue and the fact that normal breast tissue, benign lesions and breast cancers all have similar “densities”, making lesion detection more difficult. We ideally need 3-D imaging for imaging the 3-D breast. MRI is 3-D, whole breast ultrasound is 3-D, digital breast tomosynthesis is called 3-D but is really “pseudo 3-D” due to poor resolution along the depth-direction. Also, and importantly, we need to be able to administer intravenous contrast agents for optimal imaging, similar to other organ systems in the body. Dedicated breast CT allows for 3-D imaging of the uncompressed breast. In current designs, the patient is positioned prone on the table and the breast is pendant through an aperture and the scan takes approximately 10 seconds [O’Connell et al., AJR 195: 496–509, 2010]. Almost on the heels of the invention of CT itself, work began on the development of dedicated breast CT. These early breast CT systems were used in clinical trials and the results from comparative performance evaluation of breast CT and mammography for 1625 subjects were reported in 1980 [Chang et al., Cancer 46: 939–46, 1980]. However, the technological limitations at that time stymied clinical translation for decades. Subsequent to the landmark article in 2001 [Boone et al., Radiology 221: 657–67, 2001] that demonstrated the potential feasibility in terms of radiation dose, multiple research groups are actively

  7. WE-FG-207A-05: Dedicated Breast CT as a Diagnostic Imaging Tool: Physics and Clinical Feasibility

    Energy Technology Data Exchange (ETDEWEB)

    Karellas, A. [University of Massachusetts Medical School (United States)

    2016-06-15

    Mammography-based screening has been a valuable imaging tool for the early detection of non-palpable lesions and has contributed to significant reduction in breast cancer associated mortality. However, the breast imaging community recognizes that mammography is not ideal, and in particular is inferior for women with dense breasts. Also, the 2-D projection of a 3-D organ results in tissue superposition contributing to false-positives. The sensitivity of mammography is breast-density dependent. Its sensitivity, especially in dense breasts, is low due to overlapping tissue and the fact that normal breast tissue, benign lesions and breast cancers all have similar “densities”, making lesion detection more difficult. We ideally need 3-D imaging for imaging the 3-D breast. MRI is 3-D, whole breast ultrasound is 3-D, digital breast tomosynthesis is called 3-D but is really “pseudo 3-D” due to poor resolution along the depth-direction. Also, and importantly, we need to be able to administer intravenous contrast agents for optimal imaging, similar to other organ systems in the body. Dedicated breast CT allows for 3-D imaging of the uncompressed breast. In current designs, the patient is positioned prone on the table and the breast is pendant through an aperture and the scan takes approximately 10 seconds [O’Connell et al., AJR 195: 496–509, 2010]. Almost on the heels of the invention of CT itself, work began on the development of dedicated breast CT. These early breast CT systems were used in clinical trials and the results from comparative performance evaluation of breast CT and mammography for 1625 subjects were reported in 1980 [Chang et al., Cancer 46: 939–46, 1980]. However, the technological limitations at that time stymied clinical translation for decades. Subsequent to the landmark article in 2001 [Boone et al., Radiology 221: 657–67, 2001] that demonstrated the potential feasibility in terms of radiation dose, multiple research groups are actively

  8. Design, Implementation, and Characterization of a Dedicated Breast Computed Mammotomography System for Enhanced Lesion Imaging

    National Research Council Canada - National Science Library

    McKinley, Randolph L

    2006-01-01

    .... Half cone-beam orbits have been implemented and investigated and have indicated they are feasible for a wide range of breast sizes. Future studies will focus on characterizing the system in terms of dose efficiency, contrast sensitivity, and evaluation for a range of breast sizes and compositions. Patient bed optimization will also be investigated.

  9. Monte Carlo evaluation of glandular dose in cone-beam X-ray computed tomography dedicated to the breast: Homogeneous and heterogeneous breast models.

    Science.gov (United States)

    Sarno, Antonio; Mettivier, Giovanni; Tucciariello, Raffaele M; Bliznakova, Kristina; Boone, John M; Sechopoulos, Ioannis; Di Lillo, Francesca; Russo, Paolo

    2018-06-07

    In cone-beam computed tomography dedicated to the breast (BCT), the mean glandular dose (MGD) is the dose metric of reference, evaluated from the measured air kerma by means of normalized glandular dose coefficients (DgN CT ). This work aimed at computing, for a simple breast model, a set of DgN CT values for monoenergetic and polyenergetic X-ray beams, and at validating the results vs. those for patient specific digital phantoms from BCT scans. We developed a Monte Carlo code for calculation of monoenergetic DgN CT coefficients (energy range 4.25-82.25 keV). The pendant breast was modelled as a cylinder of a homogeneous mixture of adipose and glandular tissue with glandular fractions by mass of 0.1%, 14.3%, 25%, 50% or 100%, enveloped by a 1.45 mm-thick skin layer. The breast diameter ranged between 8 cm and 18 cm. Then, polyenergetic DgN CT coefficients were analytically derived for 49-kVp W-anode spectra (half value layer 1.25-1.50 mm Al), as in a commercial BCT scanner. We compared the homogeneous models to 20 digital phantoms produced from classified 3D breast images. Polyenergetic DgN CT resulted 13% lower than most recent published data. The comparison vs. patient specific breast phantoms showed that the homogeneous cylindrical model leads to a DgN CT percentage difference between -15% and +27%, with an average overestimation of 8%. A dataset of monoenergetic and polyenergetic DgN CT coefficients for BCT was provided. Patient specific breast models showed a different volume distribution of glandular dose and determined a DgN CT 8% lower, on average, than homogeneous breast model. Copyright © 2018 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

  10. Interpretation of digital breast tomosynthesis: preliminary study on comparison with picture archiving and communication system (PACS) and dedicated workstation.

    Science.gov (United States)

    Kim, Young Seon; Chang, Jung Min; Yi, Ann; Shin, Sung Ui; Lee, Myung Eun; Kim, Won Hwa; Cho, Nariya; Moon, Woo Kyung

    2017-08-01

    To compare the diagnostic accuracy and efficiency in the interpretation of digital breast tomosynthesis (DBT) images using a picture archiving and communication system (PACS) and a dedicated workstation. 97 DBT images obtained for screening or diagnostic purposes were stored in both a workstation and a PACS and evaluated in combination with digital mammography by three independent radiologists retrospectively. Breast Imaging-Reporting and Data System final assessments and likelihood of malignancy (%) were assigned and the interpretation time when using the workstation and PACS was recorded. Receiver operating characteristic curve analysis, sensitivities and specificities were compared with histopathological examination and follow-up data as a reference standard. Area under the receiver operating characteristic curve values for cancer detection (0.839 vs 0.815, p = 0.6375) and sensitivity (81.8% vs 75.8%, p = 0.2188) showed no statistically significant differences between the workstation and PACS. However, specificity was significantly higher when analysing on the workstation than when using PACS (83.7% vs 76.9%, p = 0.009). When evaluating DBT images using PACS, only one case was deemed necessary to be reanalysed using the workstation. The mean time to interpret DBT images on PACS (1.68 min/case) was significantly longer than that to interpret on the workstation (1.35 min/case) (p < 0.0001). Interpretation of DBT images using PACS showed comparable diagnostic performance to a dedicated workstation, even though it required a longer reading time. Advances in knowledge: Interpretation of DBT images using PACS is an alternative to evaluate the images when a dedicated workstation is not available.

  11. Three dimensional dose distribution comparison of simple and complex acquisition trajectories in dedicated breast CT

    Energy Technology Data Exchange (ETDEWEB)

    Shah, Jainil P., E-mail: jainil.shah@duke.edu [Department of Biomedical Engineering, Duke University, Durham, North Carolina 27705 and Multi Modality Imaging Lab, Duke University Medical Center, Durham, North Carolina 27710 (United States); Mann, Steve D. [Medical Physics Graduate Program, Duke University Medical Center, Durham, North Carolina 27705 and Multi Modality Imaging Lab, Duke University Medical Center, Durham, North Carolina 27710 (United States); McKinley, Randolph L. [ZumaTek, Inc., Research Triangle Park, North Carolina 27709 (United States); Tornai, Martin P. [Department of Biomedical Engineering, Duke University, Durham, North Carolina 27705 (United States); Medical Physics Graduate Program, Duke University Medical Center, Durham, North Carolina 27705 (United States); Multi Modality Imaging Lab, Duke University Medical Center, Durham, North Carolina 27710 (United States)

    2015-08-15

    Purpose: A novel breast CT system capable of arbitrary 3D trajectories has been developed to address cone beam sampling insufficiency as well as to image further into the patient’s chest wall. The purpose of this study was to characterize any trajectory-related differences in 3D x-ray dose distribution in a pendant target when imaged with different orbits. Methods: Two acquisition trajectories were evaluated: circular azimuthal (no-tilt) and sinusoidal (saddle) orbit with ±15° tilts around a pendant breast, using Monte Carlo simulations as well as physical measurements. Simulations were performed with tungsten (W) filtration of a W-anode source; the simulated source flux was normalized to the measured exposure of a W-anode source. A water-filled cylindrical phantom was divided into 1 cm{sup 3} voxels, and the cumulative energy deposited was tracked in each voxel. Energy deposited per voxel was converted to dose, yielding the 3D distributed dose volumes. Additionally, three cylindrical phantoms of different diameters (10, 12.5, and 15 cm) and an anthropomorphic breast phantom, initially filled with water (mimicking pure fibroglandular tissue) and then with a 75% methanol-25% water mixture (mimicking 50–50 fibroglandular-adipose tissues), were used to simulate the pendant breast geometry and scanned on the physical system. Ionization chamber calibrated radiochromic film was used to determine the dose delivered in a 2D plane through the center of the volume for a fully 3D CT scan using the different orbits. Results: Measured experimental results for the same exposure indicated that the mean dose measured throughout the central slice for different diameters ranged from 3.93 to 5.28 mGy, with the lowest average dose measured on the largest cylinder with water mimicking a homogeneously fibroglandular breast. These results align well with the cylinder phantom Monte Carlo studies which also showed a marginal difference in dose delivered by a saddle trajectory in the

  12. Three dimensional dose distribution comparison of simple and complex acquisition trajectories in dedicated breast CT

    International Nuclear Information System (INIS)

    Shah, Jainil P.; Mann, Steve D.; McKinley, Randolph L.; Tornai, Martin P.

    2015-01-01

    Purpose: A novel breast CT system capable of arbitrary 3D trajectories has been developed to address cone beam sampling insufficiency as well as to image further into the patient’s chest wall. The purpose of this study was to characterize any trajectory-related differences in 3D x-ray dose distribution in a pendant target when imaged with different orbits. Methods: Two acquisition trajectories were evaluated: circular azimuthal (no-tilt) and sinusoidal (saddle) orbit with ±15° tilts around a pendant breast, using Monte Carlo simulations as well as physical measurements. Simulations were performed with tungsten (W) filtration of a W-anode source; the simulated source flux was normalized to the measured exposure of a W-anode source. A water-filled cylindrical phantom was divided into 1 cm"3 voxels, and the cumulative energy deposited was tracked in each voxel. Energy deposited per voxel was converted to dose, yielding the 3D distributed dose volumes. Additionally, three cylindrical phantoms of different diameters (10, 12.5, and 15 cm) and an anthropomorphic breast phantom, initially filled with water (mimicking pure fibroglandular tissue) and then with a 75% methanol-25% water mixture (mimicking 50–50 fibroglandular-adipose tissues), were used to simulate the pendant breast geometry and scanned on the physical system. Ionization chamber calibrated radiochromic film was used to determine the dose delivered in a 2D plane through the center of the volume for a fully 3D CT scan using the different orbits. Results: Measured experimental results for the same exposure indicated that the mean dose measured throughout the central slice for different diameters ranged from 3.93 to 5.28 mGy, with the lowest average dose measured on the largest cylinder with water mimicking a homogeneously fibroglandular breast. These results align well with the cylinder phantom Monte Carlo studies which also showed a marginal difference in dose delivered by a saddle trajectory in the

  13. Design study of a high-resolution breast-dedicated PET system built from cadmium zinc telluride detectors

    International Nuclear Information System (INIS)

    Peng Hao; Levin, Craig S

    2010-01-01

    We studied the performance of a dual-panel positron emission tomography (PET) camera dedicated to breast cancer imaging using Monte Carlo simulation. The proposed system consists of two 4 cm thick 12 x 15 cm 2 area cadmium zinc telluride (CZT) panels with adjustable separation, which can be put in close proximity to the breast and/or axillary nodes. Unique characteristics distinguishing the proposed system from previous efforts in breast-dedicated PET instrumentation are the deployment of CZT detectors with superior spatial and energy resolution, using a cross-strip electrode readout scheme to enable 3D positioning of individual photon interaction coordinates in the CZT, which includes directly measured photon depth-of-interaction (DOI), and arranging the detector slabs edge-on with respect to incoming 511 keV photons for high photon sensitivity. The simulation results show that the proposed CZT dual-panel PET system is able to achieve superior performance in terms of photon sensitivity, noise equivalent count rate, spatial resolution and lesion visualization. The proposed system is expected to achieve ∼32% photon sensitivity for a point source at the center and a 4 cm panel separation. For a simplified breast phantom adjacent to heart and torso compartments, the peak noise equivalent count (NEC) rate is predicted to be ∼94.2 kcts s -1 (breast volume: 720 cm 3 and activity concentration: 3.7 kBq cm -3 ) for a ∼10% energy window around 511 keV and ∼8 ns coincidence time window. The system achieves 1 mm intrinsic spatial resolution anywhere between the two panels with a 4 cm panel separation if the detectors have DOI resolution less than 2 mm. For a 3 mm DOI resolution, the system exhibits excellent sphere resolution uniformity (σ rms /mean) ≤ 10%) across a 4 cm width FOV. Simulation results indicate that the system exhibits superior hot sphere visualization and is expected to visualize 2 mm diameter spheres with a 5:1 activity concentration ratio within

  14. Molecular Imaging Probes for Diagnosis and Therapy Evaluation of Breast Cancer

    Directory of Open Access Journals (Sweden)

    Qingqing Meng

    2013-01-01

    Full Text Available Breast cancer is a major cause of cancer death in women where early detection and accurate assessment of therapy response can improve clinical outcomes. Molecular imaging, which includes PET, SPECT, MRI, and optical modalities, provides noninvasive means of detecting biological processes and molecular events in vivo. Molecular imaging has the potential to enhance our understanding of breast cancer biology and effects of drug action during both preclinical and clinical phases of drug development. This has led to the identification of many molecular imaging probes for key processes in breast cancer. Hormone receptors, growth factor receptor, and angiogenic factors, such as ER, PR, HER2, and VEGFR, have been adopted as imaging targets to detect and stage the breast cancer and to monitor the treatment efficacy. Receptor imaging probes are usually composed of targeting moiety attached to a signaling component such as a radionuclide that can be detected using dedicated instruments. Current molecular imaging probes involved in breast cancer diagnosis and therapy evaluation are reviewed, and future of molecular imaging for the preclinical and clinical is explained.

  15. Early Detection of Breast Cancer Using Molecular Beacons

    National Research Council Canada - National Science Library

    Yang, Lily

    2008-01-01

    .... We proposed to use molecular beacon technology to detect the level of expression of several biomarker genes that are highly expressed in breast cancer cells but not in normal breast epithelial cells...

  16. WE-DE-207B-11: Implementation of Size-Specific 3D Beam Modulation Filters On a Dedicated Breast CT Platform Using Breast Immobilization

    Energy Technology Data Exchange (ETDEWEB)

    Hernandez, A [Department of Radiology, Biomedical Engineering Graduate Group, University of California Davis, Sacramento, CA (United States); Boone, J [Departments of Radiology and Biomedical Engineering, University of California Davis, Sacramento, CA (United States)

    2016-06-15

    Purpose: To implement a 3D beam modulation filter (3D-BMF) in dedicated breast CT (bCT) and develop a method for conforming the patient’s breast to a pre-defined shape, optimizing the effects of the filter. This work expands on previous work reporting the methodology for designing a 3D-BMF that can spare unnecessary dose and improve signal equalization at the detector by preferentially filtering the beam in the thinner anterior and peripheral breast regions. Methods: Effective diameter profiles were measured for 219 segmented bCT images, grouped into volume quintiles, and averaged within each group to represent the range of breast sizes found clinically. These profiles were then used to generate five size-specific computational phantoms and fabricate five size-specific UHMW phantoms. Each computational phantom was utilized for designing a size-specific 3D-BMF using previously reported methods. Glandular dose values and projection images were simulated in MCNP6 with and without the 3DBMF using the system specifications of our prototype bCT scanner “Doheny”. Lastly, thermoplastic was molded around each of the five phantom sizes and used to produce a series of breast immobilizers for use in conforming the patient’s breast during bCT acquisition. Results: After incorporating the 3D-BMF, MC simulations estimated an 80% average reduction in the detector dynamic range requirements across all phantom sizes. The glandular dose was reduced on average 57% after normalizing by the number of quanta reaching the detector under the thickest region of the breast. Conclusion: A series of bCT-derived breast phantoms were used to design size-specific 3D-BMFs and breast immobilizers that can be used on the bCT platform to conform the patient’s breast and therefore optimally exploit the benefits of the 3D-BMF. Current efforts are focused on fabricating several prototype 3D-BMFs and performing phantom scans on Doheny for MC simulation validation and image quality analysis

  17. WE-DE-207B-11: Implementation of Size-Specific 3D Beam Modulation Filters On a Dedicated Breast CT Platform Using Breast Immobilization

    International Nuclear Information System (INIS)

    Hernandez, A; Boone, J

    2016-01-01

    Purpose: To implement a 3D beam modulation filter (3D-BMF) in dedicated breast CT (bCT) and develop a method for conforming the patient’s breast to a pre-defined shape, optimizing the effects of the filter. This work expands on previous work reporting the methodology for designing a 3D-BMF that can spare unnecessary dose and improve signal equalization at the detector by preferentially filtering the beam in the thinner anterior and peripheral breast regions. Methods: Effective diameter profiles were measured for 219 segmented bCT images, grouped into volume quintiles, and averaged within each group to represent the range of breast sizes found clinically. These profiles were then used to generate five size-specific computational phantoms and fabricate five size-specific UHMW phantoms. Each computational phantom was utilized for designing a size-specific 3D-BMF using previously reported methods. Glandular dose values and projection images were simulated in MCNP6 with and without the 3DBMF using the system specifications of our prototype bCT scanner “Doheny”. Lastly, thermoplastic was molded around each of the five phantom sizes and used to produce a series of breast immobilizers for use in conforming the patient’s breast during bCT acquisition. Results: After incorporating the 3D-BMF, MC simulations estimated an 80% average reduction in the detector dynamic range requirements across all phantom sizes. The glandular dose was reduced on average 57% after normalizing by the number of quanta reaching the detector under the thickest region of the breast. Conclusion: A series of bCT-derived breast phantoms were used to design size-specific 3D-BMFs and breast immobilizers that can be used on the bCT platform to conform the patient’s breast and therefore optimally exploit the benefits of the 3D-BMF. Current efforts are focused on fabricating several prototype 3D-BMFs and performing phantom scans on Doheny for MC simulation validation and image quality analysis

  18. Breast Cancer Molecular Subtypes Among Moroccan Women

    Directory of Open Access Journals (Sweden)

    Wissal Mahir

    2016-12-01

    Full Text Available Introduction: Breast cancer remains despite the therapeutic progress, the leading cause of death by cancer among women. It represents a group of very heterogeneous clinical, histopathological and molecular diseases. Molecular heterogeneity has been demonstrated by genomic analysis, even for similar histology cancers. Four subgroups of breast carcinomas are distinguished: Luminal A, Luminal B, HER2 over expression and Basal - like. The Immuno-histo-chemical analysis useip (estrogen receptors RE, the PR (progesterone receptors, the ((Human Epidermal Growth Factor Receptor-2, the Ki67 (proliferation marker HER2, CK5/6 has shown a subdivision into subgroups similar to those found by genomic analysis. These subgroups are different from the point of view of clinical course and response to adjuvant treatment.Objectives: The aim of this work is to study the molecular profile of the breast cancers by immunostaining on Moroccan series to a classification with a prognostic value allowing a treatment tailored to each group of patients. Furthermore, the molecular subgroups were correlated to other clinical and histological factors.Material and methods: It is a prospective study of the laboratory of Anatomy and Pathologic cytology of the children's Hospital, the service I of the maternity hospital in Rabat and in cooperation with the United Nations Centre of pathological anatomy. To do this, 88 cases of breast cancer together were diagnosed between January 1, 2010 and December 31, 2014, taking a period of five years. All tissue samples made subject study of Immuno-histo-chemistry with the following markers: RE, PR, HER2 and Ki67. Only negative triple cases (HR and HER2 negative benefited from an additional marking with CK5/6 and EGFR to set the basal profile.Results: Series of 88 cases of mammary carcinomas observed on operating parts, ranged in age between 28 and 84 years old, with an average of 51 ± 12, 8. Carcinoma infiltrating non-specific (DOCTORS was

  19. Prognostic molecular markers in early breast cancer

    International Nuclear Information System (INIS)

    Esteva, Francisco J; Hortobagyi, Gabriel N

    2004-01-01

    A multitude of molecules involved in breast cancer biology have been studied as potential prognostic markers. In the present review we discuss the role of established molecular markers, as well as potential applications of emerging new technologies. Those molecules used routinely to make treatment decisions in patients with early-stage breast cancer include markers of proliferation (e.g. Ki-67), hormone receptors, and the human epidermal growth factor receptor 2. Tumor markers shown to have prognostic value but not used routinely include cyclin D 1 and cyclin E, urokinase-like plasminogen activator/plasminogen activator inhibitor, and cathepsin D. The level of evidence for other molecular markers is lower, in part because most studies were retrospective and not adequately powered, making their findings unsuitable for choosing treatments for individual patients. Gene microarrays have been successfuly used to classify breast cancers into subtypes with specific gene expression profiles and to evaluate prognosis. RT-PCR has also been used to evaluate expression of multiple genes in archival tissue. Proteomics technologies are in development

  20. Texture analysis of high-resolution dedicated breast {sup 18}F-FDG PET images correlates with immunohistochemical factors and subtype of breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Moscoso, Alexis; Dominguez-Prado, Ines; Herranz, Michel; Argibay, Sonia; Silva-Rodriguez, Jesus [Complexo Hospitalario Universitario de Santiago de Compostela CHUS-IDIS, Nuclear Medicine Department and Molecular Imaging Group, Santiago de Compostela (Spain); Ruibal, Alvaro [Complexo Hospitalario Universitario de Santiago de Compostela CHUS-IDIS, Nuclear Medicine Department and Molecular Imaging Group, Santiago de Compostela (Spain); University of Santiago de Compostela (USC), Molecular Imaging Group, Department of Radiology, Faculty of Medicine, Santiago de Compostela (Spain); Fundacion Tejerina, Madrid (Spain); Fernandez-Ferreiro, Anxo [Complexo Hospitalario Universitario de Santiago de Compostela CHUS-IDIS, Pharmacy Department and Pharmacology Group, Santiago de Compostela (Spain); Albaina, Luis [University Hospital A Coruna (SERGAS), Department of General Surgery, A Coruna (Spain); Pardo-Montero, Juan [Complexo Hospitalario Universitario de Santiago de Compostela CHUS-IDIS, Nuclear Medicine Department and Molecular Imaging Group, Santiago de Compostela (Spain); Complexo Hospitalario Universitario de Santiago de Compostela (CHUS), Medical Physics Department, Santiago de Compostela (Spain); Aguiar, Pablo [Complexo Hospitalario Universitario de Santiago de Compostela CHUS-IDIS, Nuclear Medicine Department and Molecular Imaging Group, Santiago de Compostela (Spain); University of Santiago de Compostela (USC), Molecular Imaging Group, Department of Radiology, Faculty of Medicine, Santiago de Compostela (Spain)

    2018-02-15

    This study aims to determine whether PET textural features measured with a new dedicated breast PET scanner reflect biological characteristics of breast tumors. One hundred and thirty-nine breast tumors from 127 consecutive patients were included in this analysis. All of them underwent a {sup 18}F-FDG PET scan before treatment. Well-known PET quantitative parameters such as SUV{sub m} {sub a} {sub x}, SUV{sub m} {sub e} {sub a} {sub n}, metabolically active tumor volume (MATV) and total lesion glycolysis (TLG) were extracted. Together with these parameters, local, regional, and global heterogeneity descriptors, which included five textural features (TF), were computed. Immunohistochemical classification of breast cancer considered five subtypes: luminal A like (LA), luminal B like/HER2 - (LB -), luminal B like/HER2+ (LB+), HER2-positive-non-luminal (HER2pnl), and triple negative (TN). Associations between PET features and tumor characteristics were assessed using non-parametric hypothesis tests. Along with well-established associations, new correlations were found. HER2-positive tumors had significantly higher uptake (p < 0.001, AUCs > 0.70) and presented different global and regional heterogeneity (p = 0.002, p = 0.016, respectively, AUCs < 0.70). Nine out of ten analyzed features were significantly associated with immunohistochemical subtype. Uptake was lower for LA tumors (p < 0.001) with AUCs ranging from 0.71 to 0.88 for each subgroup comparison. Heterogeneity metrics were significantly associated when comparing LA and LB - (p < 0.01), being regional heterogeneity metrics more discriminative than any other parameter (AUC = 0.80 compared to AUC = 0.71 for SUV). LB+ and HER2pnl tumors also showed more regional heterogeneity than LA tumors (AUCs = 0.79 and 0.84, respectively). After comparison with whole-body PET studies, we observed an overall improvement in the classification ability of both non-heterogeneity metrics and textural features. PET parameters

  1. Multicenter study for the evaluation of a dedicated biopsy device for MR-guided vacuum biopsy of the breast

    International Nuclear Information System (INIS)

    Perlet, C.; Sittek, H.; Schneider, P.; Reiser, M.; Heinig, A.; Stets, C.; Heywang-Koebrunner, S.H.; Prat, X.; Lamarque, J.; Taourel, P.; Casselman, J.; Baath, L.; Anderson, I.

    2002-01-01

    The purpose of this multicenter study was to determine the accuracy and clinical value of a dedicated breast biopsy system which allows for MR-guided vacuum biopsy (VB) of contrast-enhancing lesions. In five European centers, MR-guided 11-gauge VB was performed on 341 lesions. In 7 cases VB was unsuccessful. This was immediately realized on postinterventional images or direct follow-up combined with histopathology-imaging correlation; thus, a false-negative diagnosis was avoided. Histology of 334 successful biopsies yielded 84 (25%) malignancies, 17 (5%) atypical ductal hyperplasias, and 233 (70%) benign entities. Verification of malignant or borderline lesions included reexcision of the biopsy cavity. Benign histologic biopsy results were verified by retrospective correlation with the pre- and postinterventional MRI and by subsequent follow-up. Our results indicate that MR-guided VB, in combination with the dedicated biopsy coil, offers the possibility to accurately diagnose even very small lesions that can only be visualized or localized by MRI. (orig.)

  2. Bowtie filters for dedicated breast CT: Analysis of bowtie filter material selection

    Energy Technology Data Exchange (ETDEWEB)

    Kontson, Kimberly, E-mail: Kimberly.Kontson@fda.hhs.gov; Jennings, Robert J. [Department of Bioengineering, University of Maryland, College Park, Maryland 20742 and Division of Imaging and Applied Mathematics, Office of Science and Engineering Laboratories, Center for Devices and Radiological Health, U.S. Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, Maryland 20993 (United States)

    2015-09-15

    , and scatter were investigated. Results: Analytical calculations with and without each bowtie filter show that some materials for a given design produce bowtie filters that are too large for implementation in breast CT scanners or too small to accurately manufacture. Results also demonstrate the ability to manipulate the energy fluence distribution (dynamic range) by using different materials, or different combinations of materials, for a given bowtie filter design. This feature is especially advantageous when using photon counting detector technology. Monte Carlo simulation results from PENELOPE show that all studied material choices for bowtie design #2 achieve nearly uniform dose distribution, noise uniformity index less than 5%, and nearly uniform scatter-to-primary ratio. These same features can also be obtained using certain materials with bowtie designs #1 and #3. Conclusions: With the three bowtie filter designs used in this work, the selection of material is an important design consideration. An appropriate material choice can improve image quality, dose uniformity, and dynamic range.

  3. Bowtie filters for dedicated breast CT: Analysis of bowtie filter material selection

    International Nuclear Information System (INIS)

    Kontson, Kimberly; Jennings, Robert J.

    2015-01-01

    , and scatter were investigated. Results: Analytical calculations with and without each bowtie filter show that some materials for a given design produce bowtie filters that are too large for implementation in breast CT scanners or too small to accurately manufacture. Results also demonstrate the ability to manipulate the energy fluence distribution (dynamic range) by using different materials, or different combinations of materials, for a given bowtie filter design. This feature is especially advantageous when using photon counting detector technology. Monte Carlo simulation results from PENELOPE show that all studied material choices for bowtie design #2 achieve nearly uniform dose distribution, noise uniformity index less than 5%, and nearly uniform scatter-to-primary ratio. These same features can also be obtained using certain materials with bowtie designs #1 and #3. Conclusions: With the three bowtie filter designs used in this work, the selection of material is an important design consideration. An appropriate material choice can improve image quality, dose uniformity, and dynamic range

  4. WE-DE-207B-12: Scatter Correction for Dedicated Cone Beam Breast CT Based On a Forward Projection Model

    Energy Technology Data Exchange (ETDEWEB)

    Shi, L; Zhu, L [Georgia Institute of Technology, Atlanta, GA (Georgia); Vedantham, S; Karellas, A [University of Massachusetts Medical School, Worcester, MA (United States)

    2016-06-15

    Purpose: The image quality of dedicated cone-beam breast CT (CBBCT) is fundamentally limited by substantial x-ray scatter contamination, resulting in cupping artifacts and contrast-loss in reconstructed images. Such effects obscure the visibility of soft-tissue lesions and calcifications, which hinders breast cancer detection and diagnosis. In this work, we propose to suppress x-ray scatter in CBBCT images using a deterministic forward projection model. Method: We first use the 1st-pass FDK-reconstructed CBBCT images to segment fibroglandular and adipose tissue. Attenuation coefficients are assigned to the two tissues based on the x-ray spectrum used for imaging acquisition, and is forward projected to simulate scatter-free primary projections. We estimate the scatter by subtracting the simulated primary projection from the measured projection, and then the resultant scatter map is further refined by a Fourier-domain fitting algorithm after discarding untrusted scatter information. The final scatter estimate is subtracted from the measured projection for effective scatter correction. In our implementation, the proposed scatter correction takes 0.5 seconds for each projection. The method was evaluated using the overall image spatial non-uniformity (SNU) metric and the contrast-to-noise ratio (CNR) with 5 clinical datasets of BI-RADS 4/5 subjects. Results: For the 5 clinical datasets, our method reduced the SNU from 7.79% to 1.68% in coronal view and from 6.71% to 3.20% in sagittal view. The average CNR is improved by a factor of 1.38 in coronal view and 1.26 in sagittal view. Conclusion: The proposed scatter correction approach requires no additional scans or prior images and uses a deterministic model for efficient calculation. Evaluation with clinical datasets demonstrates the feasibility and stability of the method. These features are attractive for clinical CBBCT and make our method distinct from other approaches. Supported partly by NIH R21EB019597, R21CA134128

  5. Molecular basis of the triple negative breast cancer

    Directory of Open Access Journals (Sweden)

    Ayse Feyda Nursal

    2015-06-01

    Full Text Available Breast cancer is the most common type of cancer in women and more than 1 million breast cancer cases are diagnosed each year all over the world. Breast cancer is a complex and heterogeneous disease in terms of its molecular structure, mutation type, metastase properties, clinical course and therapeutic response. Breast cancer is divided into subtypes based on expression properties of molecular markers as estrogen receptor, progestron receptor, human epidermal growth factor receptor 2. Triple-negative breast cancer is characterized by the lack of tumors that estrogen receptor, progestron receptor, human epidermal growth factor receptor 2 gene expression. These type of tumors lead to agressive clinical course due to unresponsiveness to systemic endocrine therapy and poor prognosis. Triple negative breast cancer constitutes 10-20% of all breast cancers. It affects generally young and African-American women. Triple negative breast cancer have several subtypes based on the gene expression properties. The majority of them are basal-like breast cancers. In this review, current literature is revised and summarized with respect to the molecular basis of triple negative cancers. [Archives Medical Review Journal 2015; 24(2.000: 251-259

  6. Physical effects of mechanical design parameters on photon sensitivity and spatial resolution performance of a breast-dedicated PET system.

    Science.gov (United States)

    Spanoudaki, V C; Lau, F W Y; Vandenbroucke, A; Levin, C S

    2010-11-01

    This study aims to address design considerations of a high resolution, high sensitivity positron emission tomography scanner dedicated to breast imaging. The methodology uses a detailed Monte Carlo model of the system structures to obtain a quantitative evaluation of several performance parameters. Special focus was given to the effect of dense mechanical structures designed to provide mechanical robustness and thermal regulation to the minuscule and temperature sensitive detectors. For the energies of interest around the photopeak (450-700 keV energy window), the simulation results predict a 6.5% reduction in the single photon detection efficiency and a 12.5% reduction in the coincidence photon detection efficiency in the case that the mechanical structures are interspersed between the detectors. However for lower energies, a substantial increase in the number of detected events (approximately 14% and 7% for singles at a 100-200 keV energy window and coincidences at a lower energy threshold of 100 keV, respectively) was observed with the presence of these structures due to backscatter. The number of photon events that involve multiple interactions in various crystal elements is also affected by the presence of the structures. For photon events involving multiple interactions among various crystal elements, the coincidence photon sensitivity is reduced by as much as 20% for a point source at the center of the field of view. There is no observable effect on the intrinsic and the reconstructed spatial resolution and spatial resolution uniformity. Mechanical structures can have a considerable effect on system sensitivity, especially for systems processing multi-interaction photon events. This effect, however, does not impact the spatial resolution. Various mechanical structure designs are currently under evaluation in order to achieve optimum trade-off between temperature stability, accurate detector positioning, and minimum influence on system performance.

  7. Molecular biology of breast cancer metastasis Molecular expression of vascular markers by aggressive breast cancer cells

    International Nuclear Information System (INIS)

    Hendrix, Mary JC; Seftor, Elisabeth A; Kirschmann, Dawn A; Seftor, Richard EB

    2000-01-01

    During embryogenesis, the formation of primary vascular networks occurs via the processes of vasculogenesis and angiogenesis. In uveal melanoma, vasculogenic mimicry describes the 'embryonic-like' ability of aggressive, but not nonaggressive, tumor cells to form networks surrounding spheroids of tumor cells in three-dimensional culture; these recapitulate the patterned networks seen in patients' aggressive tumors and correlates with poor prognosis. The molecular profile of these aggressive tumor cells suggests that they have a deregulated genotype, capable of expressing vascular phenotypes. Similarly, the embryonic-like phenotype expressed by the aggressive human breast cancer cells is associated with their ability to express a variety of vascular markers. These studies may offer new insights for consideration in breast cancer diagnosis and therapeutic intervention strategies

  8. Molecular biology of breast cancer stem cells: potential clinical applications.

    Science.gov (United States)

    Nguyen, Nam P; Almeida, Fabio S; Chi, Alex; Nguyen, Ly M; Cohen, Deirdre; Karlsson, Ulf; Vinh-Hung, Vincent

    2010-10-01

    Breast cancer stem cells (CSC) have been postulated recently as responsible for failure of breast cancer treatment. The purpose of this study is to review breast CSCs molecular biology with respect to their mechanism of resistance to conventional therapy, and to develop treatment strategies that may improve survival of breast cancer patients. A literature search has identified in vitro and in vivo studies of breast CSCs. Breast CSCs overexpress breast cancer resistance protein (BCRP) which allows cancer cells to transport actively chemotherapy agents out of the cells. Radioresistance is modulated through activation of Wnt signaling pathway and overexpression of genes coding for glutathione. Lapatinib can selectively target HER-2 positive breast CSCs and improves disease-free survival in these patients. Metformin may target basal type breast CSCs. Parthenolide and oncolytic viruses are promising targeting agents for breast CSCs. Future clinical trials for breast cancer should include anti-cancer stem cells targeting agents in addition to conventional chemotherapy. Hypofractionation radiotherapy may be indicated for residual disease post chemotherapy. 2010 Elsevier Ltd. All rights reserved.

  9. Breast cancer lung metastasis: Molecular biology and therapeutic implications.

    Science.gov (United States)

    Jin, Liting; Han, Bingchen; Siegel, Emily; Cui, Yukun; Giuliano, Armando; Cui, Xiaojiang

    2018-03-26

    Distant metastasis accounts for the vast majority of deaths in patients with cancer. Breast cancer exhibits a distinct metastatic pattern commonly involving bone, liver, lung, and brain. Breast cancer can be divided into different subtypes based on gene expression profiles, and different breast cancer subtypes show preference to distinct organ sites of metastasis. Luminal breast tumors tend to metastasize to bone while basal-like breast cancer (BLBC) displays a lung tropism of metastasis. However, the mechanisms underlying this organ-specific pattern of metastasis still remain to be elucidated. In this review, we will summarize the recent advances regarding the molecular signaling pathways as well as the therapeutic strategies for treating breast cancer lung metastasis.

  10. The implications of breast cancer molecular phenotype for radiation oncology

    Directory of Open Access Journals (Sweden)

    Shirin eSioshansi

    2011-06-01

    Full Text Available The identification of distinct molecular subtypes of breast cancer has advanced the understanding and treatment of breast cancer by providing insight into prognosis, patterns of recurrence and effectiveness of therapy. The prognostic significance of molecular phenotype with regard to distant recurrences and overall survival are well established in the literature and has been readily incorporated into systemic therapy management decisions. However, despite the accumulating data suggesting similar prognostic significance for locoregional recurrence, integration of molecular phenotype into local management decision making has lagged. Although there are some conflicting reports, collectively the literature supports a low risk of local recurrence in the hormone receptor positive luminal subtypes compared to hormone receptor negative subtypes (triple negative and HER2-enriched. The development of targeted therapies, such as trastuzumab for the treatment of HER2-enriched subtype, has been shown to mitigate the increased risk of local recurrence. Unfortunately, no such remedy exists to address the increased risk of local recurrence for patients with triple negative tumors, making it a clinical challenge for radiation oncologists. In this review we discuss the correlation between molecular subtype and local recurrence following either breast conservation therapy or mastectomy. We also explore the possible mechanisms for increased local recurrence in triple negative breast cancer and radiotherapeutic implications for this population, such as the safety of breast conservation, consideration of dose escalation and the appropriateness of accelerated partial breast irradiation.

  11. The Implications of Breast Cancer Molecular Phenotype for Radiation Oncology

    Energy Technology Data Exchange (ETDEWEB)

    Sioshansi, Shirin [Department of Radiation Oncology, Tufts Medical Center, Tufts University School of Medicine, Boston, MA (United States); Department of Radiation Oncology, Rhode Island Hospital, Warren Alpert School of Medicine at Brown University, Providence, RI (United States); Huber, Kathryn E. [Department of Radiation Oncology, Tufts Medical Center, Tufts University School of Medicine, Boston, MA (United States); Wazer, David E., E-mail: dwazer@tuftsmedicalcenter.org [Department of Radiation Oncology, Tufts Medical Center, Tufts University School of Medicine, Boston, MA (United States); Department of Radiation Oncology, Rhode Island Hospital, Warren Alpert School of Medicine at Brown University, Providence, RI (United States)

    2011-06-28

    The identification of distinct molecular subtypes of breast cancer has advanced the understanding and treatment of breast cancer by providing insight into prognosis, patterns of recurrence, and effectiveness of therapy. The prognostic significance of molecular phenotype with regard to distant recurrences and overall survival are well established in the literature and has been readily incorporated into systemic therapy management decisions. However, despite the accumulating data suggesting similar prognostic significance for locoregional recurrence, integration of molecular phenotype into local management decision making has lagged. Although there are some conflicting reports, collectively the literature supports a low risk of local recurrence (LR) in the hormone receptor (HR) positive luminal subtypes compared to HR negative subtypes [triple negative (TN) and HER2-enriched]. The development of targeted therapies, such as trastuzumab for the treatment of HER2-enriched subtype, has been shown to mitigate the increased risk of LR. Unfortunately, no such remedy exists to address the increased risk of LR for patients with TN tumors, making it a clinical challenge for radiation oncologists. In this review we discuss the correlation between molecular subtype and LR following either breast conservation therapy or mastectomy. We also explore the possible mechanisms for increased LR in TN breast cancer and radiotherapeutic implications for this population, such as the safety of breast conservation, consideration of dose escalation, and the appropriateness of accelerated partial breast irradiation.

  12. The Implications of Breast Cancer Molecular Phenotype for Radiation Oncology

    International Nuclear Information System (INIS)

    Sioshansi, Shirin; Huber, Kathryn E.; Wazer, David E.

    2011-01-01

    The identification of distinct molecular subtypes of breast cancer has advanced the understanding and treatment of breast cancer by providing insight into prognosis, patterns of recurrence, and effectiveness of therapy. The prognostic significance of molecular phenotype with regard to distant recurrences and overall survival are well established in the literature and has been readily incorporated into systemic therapy management decisions. However, despite the accumulating data suggesting similar prognostic significance for locoregional recurrence, integration of molecular phenotype into local management decision making has lagged. Although there are some conflicting reports, collectively the literature supports a low risk of local recurrence (LR) in the hormone receptor (HR) positive luminal subtypes compared to HR negative subtypes [triple negative (TN) and HER2-enriched]. The development of targeted therapies, such as trastuzumab for the treatment of HER2-enriched subtype, has been shown to mitigate the increased risk of LR. Unfortunately, no such remedy exists to address the increased risk of LR for patients with TN tumors, making it a clinical challenge for radiation oncologists. In this review we discuss the correlation between molecular subtype and LR following either breast conservation therapy or mastectomy. We also explore the possible mechanisms for increased LR in TN breast cancer and radiotherapeutic implications for this population, such as the safety of breast conservation, consideration of dose escalation, and the appropriateness of accelerated partial breast irradiation.

  13. Molecular Imaging and Precision Medicine in Breast Cancer.

    Science.gov (United States)

    Chudgar, Amy V; Mankoff, David A

    2017-01-01

    Precision medicine, basing treatment approaches on patient traits and specific molecular features of disease processes, has an important role in the management of patients with breast cancer as targeted therapies continue to improve. PET imaging offers noninvasive information that is complementary to traditional tissue biomarkers, including information about tumor burden, tumor metabolism, receptor status, and proliferation. Several PET agents that image breast cancer receptors can visually demonstrate the extent and heterogeneity of receptor-positive disease and help predict which tumors are likely to respond to targeted treatments. This review presents applications of PET imaging in the targeted treatment of breast cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Molecular Concordance Between Primary Breast Cancer and Matched Metastases

    DEFF Research Database (Denmark)

    Krøigård, Anne Bruun; Larsen, Martin Jakob; Thomassen, Mads

    2016-01-01

    Clinical management of breast cancer is increasingly personalized and based on molecular profiling. Often, primary tumors are used as proxies for systemic disease at the time of recurrence. However, recent studies have revealed substantial discordances between primary tumors and metastases, both....... The purpose of this review is to illuminate the extent of cancer genome evolution through disease progression and the degree of molecular concordance between primary breast cancers and matched metastases. We present an overview of the most prominent studies investigating the expression of endocrine receptors......, transcriptomics, and genome aberrations in primary tumors and metastases. In conclusion, biopsy of metastatic lesions at recurrence of breast cancer is encouraged to provide optimal treatment of the disease. Furthermore, molecular profiling of metastatic tissue provides invaluable mechanistic insight...

  15. Potential Use of American College of Radiology BI-RADS Mammography Atlas for Reporting and Assessing Lesions Detected on Dedicated Breast CT Imaging: Preliminary Study.

    Science.gov (United States)

    Jung, Hae Kyoung; Kuzmiak, Cherie M; Kim, Keum Won; Choi, Na Mi; Kim, Hye Jeong; Langman, Eun Lee; Yoon, Sora; Steen, Doreen; Zeng, Donglin; Gao, Fei

    2017-11-01

    Dedicated breast computed tomography (DBCT) is an emerging and promising modality for breast lesions. The objective of this study was to evaluate the potential use of applying the BI-RADS Mammography Atlas 5th Edition for reporting and assessing breast lesions on DBCT. Currently, no atlas exists for DBCT. Four radiologists trained in breast imaging were recruited in this institutional review board-approved, Health Insurance Portability and Accountability Act-compliant study. The enrolled radiologists, who were blinded to mammographic and histopathologic findings, individually reviewed 30 randomized DBCT cases that contained marked lesions. Thirty-four lesions were included in this study: 24 (70.6%) masses, 7 (20.6%) calcifications, and 3 (8.8%) architectural distortions. Eight (23.5%) lesions were malignant and 26 (76.5%) were benign. The reader was asked to specify according to the BI-RADS Mammography Atlas for each marked DBCT lesion: primary findings, features, breast density, and final assessment. We calculated readers' diagnostic performances for differentiating between benign and malignant lesions and interobserver variability for reporting and assessing lesions using a generalized estimating equation and the Fleiss kappa (κ) statistic. The estimated overall sensitivity of the readers was 0.969, and the specificity was 0.529. There were no significant differences in the sensitivity and the specificity between lesion types. For reporting the presence of a primary finding, the overall substantial agreement (κ = 0.70) was seen. In assigning the breast density and the final assessment, the overall agreement was moderate (κ = 0.53) and fair (κ = 0.30). The use of the BI-RADS Mammography Atlas 5th Edition for DBCT showed high performance and good agreement among readers. Copyright © 2017 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

  16. Biomarker assessment and molecular testing for prognostication in breast cancer.

    Science.gov (United States)

    Kos, Zuzana; Dabbs, David J

    2016-01-01

    Current treatment of breast cancer incorporates clinical, pathological and molecular data. Oestrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) define prognosis and identify tumours for targeted therapy, and remain the sole established single-molecule biomarkers defining the minimum breast cancer pathology data set. Ki67 remains one of the most promising yet controversial biomarkers in breast cancer, implemented routinely in some, but not all, pathology departments. Beyond the single-molecule biomarkers, a host of multigene expression tests have been developed to interrogate the driver pathways and biology of individual breast cancers to predict clinical outcome more accurately. A minority of these assays have entered into clinical practice. This review focuses on the established biomarkers of ER, PR and HER2, the controversial but clinically implemented biomarker Ki67 and the currently marketed gene expression signatures. © 2015 John Wiley & Sons Ltd.

  17. WE-DE-207B-10: Library-Based X-Ray Scatter Correction for Dedicated Cone-Beam Breast CT: Clinical Validation

    Energy Technology Data Exchange (ETDEWEB)

    Shi, L; Zhu, L [Georgia Institute of Technology, Atlanta, GA (Georgia); Vedantham, S; Karellas, A [University of Massachusetts Medical School, Worcester, MA (United States)

    2016-06-15

    Purpose: Scatter contamination is detrimental to image quality in dedicated cone-beam breast CT (CBBCT), resulting in cupping artifacts and loss of contrast in reconstructed images. Such effects impede visualization of breast lesions and the quantitative accuracy. Previously, we proposed a library-based software approach to suppress scatter on CBBCT images. In this work, we quantify the efficacy and stability of this approach using datasets from 15 human subjects. Methods: A pre-computed scatter library is generated using Monte Carlo simulations for semi-ellipsoid breast models and homogeneous fibroglandular/adipose tissue mixture encompassing the range reported in literature. Projection datasets from 15 human subjects that cover 95 percentile of breast dimensions and fibroglandular volume fraction were included in the analysis. Our investigations indicate that it is sufficient to consider the breast dimensions alone and variation in fibroglandular fraction does not significantly affect the scatter-to-primary ratio. The breast diameter is measured from a first-pass reconstruction; the appropriate scatter distribution is selected from the library; and, deformed by considering the discrepancy in total projection intensity between the clinical dataset and the simulated semi-ellipsoidal breast. The deformed scatter-distribution is subtracted from the measured projections for scatter correction. Spatial non-uniformity (SNU) and contrast-to-noise ratio (CNR) were used as quantitative metrics to evaluate the results. Results: On the 15 patient cases, our method reduced the overall image spatial non-uniformity (SNU) from 7.14%±2.94% (mean ± standard deviation) to 2.47%±0.68% in coronal view and from 10.14%±4.1% to 3.02% ±1.26% in sagittal view. The average contrast to noise ratio (CNR) improved by a factor of 1.49±0.40 in coronal view and by 2.12±1.54 in sagittal view. Conclusion: We demonstrate the robustness and effectiveness of a library-based scatter correction

  18. Validation of a radiosensitivity molecular signature in breast cancer

    NARCIS (Netherlands)

    S.A. Eschrich (Steven); C. Fulp (Carl); Y. Pawitan (Yudi); J.A. Foekens (John); M. Smid (Marcel); J.W.M. Martens (John); M. Echevarria (Michelle); P.S. Kamath (Patrick); J.-H. Lee (Ji-Hyun); E.E. Harris (Eleanor); J. Bergh (Jonas); J.F. Torres-Roca (Javier)

    2012-01-01

    textabstractPurpose: Previously, we developed a radiosensitivity molecular signature [radiosensitivity index (RSI)] that was clinically validated in 3 independent datasets (rectal, esophageal, and head and neck) in 118 patients. Here, we test RSI in radiotherapy (RT)-treated breast cancer patients.

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

    International Nuclear Information System (INIS)

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

    2012-01-01

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

  20. 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.

  1. Clinical application of S-Detect to breast masses on ultrasonography: A study evaluating the diagnostic performance and agreement with a dedicated breast radiologist

    International Nuclear Information System (INIS)

    Kim, Ki Wook; Kim, Eun Kyung; Yoon, Jung Hyun; Song, Mi Kyung

    2017-01-01

    The purpose of this study was to evaluate the diagnostic performance of S-Detect when applied to breast ultrasonography (US), and the agreement with an experienced radiologist specializing in breast imaging. From June to August 2015, 192 breast masses in 175 women were included. US features of the breast masses were retrospectively analyzed by a radiologist who specializes in breast imaging and S-Detect, according to the fourth edition of the American College of Radiology Breast Imaging Reporting and Data System lexicon and final assessment categories. Final assessments from S-Detect were in dichotomized form: possibly benign and possibly malignant. Kappa statistics were used to analyze the agreement between the radiologist and S-Detect. Diagnostic performance of the radiologist and S-Detect was calculated, including sensitivity, specificity, positive predictive value (PPV), negative predictive value, accuracy, and area under the receiving operator characteristics curve. Of the 192 breast masses, 72 (37.5%) were malignant, and 120 (62.5%) were benign. Benign masses among category 4a had higher rates of possibly benign assessment on S-Detect for the radiologist, 63.5% to 36.5%, respectively (P=0.797). When the cutoff was set at category 4a, the specificity, PPV, and accuracy was significantly higher in S-Detect compared to the radiologist (all P<0.05), with a higher area under the receiver operator characteristics curve of 0.725 compared to 0.653 (P=0.038). Moderate agreement (k=0.58) was seen in the final assessment between the radiologist and S-Detect. S-Detect may be used as an additional diagnostic tool to improve the specificity of breast US in clinical practice, and guide in decision making for breast masses detected on US

  2. Comparison of fan beam, slit-slat and multi-pinhole collimators for molecular breast tomosynthesis.

    Science.gov (United States)

    van Roosmalen, Jarno; Beekman, Freek J; Goorden, Marlies C

    2018-05-16

    Recently, we proposed and optimized dedicated multi-pinhole molecular breast tomosynthesis (MBT) that images a lightly compressed breast. As MBT may also be performed with other types of collimators, the aim of this paper is to optimize MBT with fan beam and slit-slat collimators and to compare its performance to that of multi-pinhole MBT to arrive at a truly optimized design. Using analytical expressions, we first optimized fan beam and slit-slat collimator parameters to reach maximum sensitivity at a series of given system resolutions. Additionally, we performed full system simulations of a breast phantom containing several tumours for the optimized designs. We found that at equal system resolution the maximum achievable sensitivity increases from pinhole to slit-slat to fan beam collimation with fan beam and slit-slat MBT having on average a 48% and 20% higher sensitivity than multi-pinhole MBT. Furthermore, by inspecting simulated images and applying a tumour-to-background contrast-to-noise (TB-CNR) analysis, we found that slit-slat collimators underperform with respect to the other collimator types. The fan beam collimators obtained a similar TB-CNR as the pinhole collimators, but the optimum was reached at different system resolutions. For fan beam collimators, a 6-8 mm system resolution was optimal in terms of TB-CNR, while with pinhole collimation highest TB-CNR was reached in the 7-10 mm range.

  3. Breast cancer molecular subtype classification using deep features: preliminary results

    Science.gov (United States)

    Zhu, Zhe; Albadawy, Ehab; Saha, Ashirbani; Zhang, Jun; Harowicz, Michael R.; Mazurowski, Maciej A.

    2018-02-01

    Radiogenomics is a field of investigation that attempts to examine the relationship between imaging characteris- tics of cancerous lesions and their genomic composition. This could offer a noninvasive alternative to establishing genomic characteristics of tumors and aid cancer treatment planning. While deep learning has shown its supe- riority in many detection and classification tasks, breast cancer radiogenomic data suffers from a very limited number of training examples, which renders the training of the neural network for this problem directly and with no pretraining a very difficult task. In this study, we investigated an alternative deep learning approach referred to as deep features or off-the-shelf network approach to classify breast cancer molecular subtypes using breast dynamic contrast enhanced MRIs. We used the feature maps of different convolution layers and fully connected layers as features and trained support vector machines using these features for prediction. For the feature maps that have multiple layers, max-pooling was performed along each channel. We focused on distinguishing the Luminal A subtype from other subtypes. To evaluate the models, 10 fold cross-validation was performed and the final AUC was obtained by averaging the performance of all the folds. The highest average AUC obtained was 0.64 (0.95 CI: 0.57-0.71), using the feature maps of the last fully connected layer. This indicates the promise of using this approach to predict the breast cancer molecular subtypes. Since the best performance appears in the last fully connected layer, it also implies that breast cancer molecular subtypes may relate to high level image features

  4. The pathology of familial breast cancer: Immunohistochemistry and molecular analysis

    International Nuclear Information System (INIS)

    Osin, Pinchas P; Lakhani, Sunil R

    1999-01-01

    Extensive studies of BRCA1- and BRCA2-associated breast tumours have been carried out in the few years since the identification of these familial breast cancer predisposing genes. The morphological studies suggest that BRCA1 tumours differ from BRCA2 tumours and from sporadic breast cancers. Recent progress in immunohistochemistry and molecular biology techniques has enabled in-depth investigation of molecular pathology of these tumours. Studies to date have investigated issues such as steroid hormone receptor expression, mutation status of tumour suppressor genes TP53 and c-erbB2, and expression profiles of cell cycle proteins p21, p27 and cyclin D 1 . Despite relative paucity of data, strong evidence of unique biological characteristics of BRCA1-associated breast cancer is accumulating. BRCA1-associated tumours appear to show an increased frequency of TP53 mutations, frequent p53 protein stabilization and absence of imunoreactivity for steroid hormone receptors. Further studies of larger number of samples of both BRCA1- and BRCA2-associated tumours are necessary to clarify and confirm these observations

  5. Progress on dedicated animal PET

    International Nuclear Information System (INIS)

    Liu Wei

    2002-01-01

    Positron emission tomography, as the leading technology providing molecular imaging of biological processes, is widely used on living laboratory animals. High-resolution dedicated animal PET scanners have been developed. Although the dedicated animal PET faces obstacles and challenges, this advanced technology would play an important role in molecular biomedicine researches, such as diseases study, medicine development, and gene therapy

  6. Mammographic Breast Density and Breast Cancer Molecular Subtypes: The Kenyan-African Aspect

    Directory of Open Access Journals (Sweden)

    Asim Jamal Shaikh

    2018-01-01

    Full Text Available Introduction. Data examining mammographic breast density (MBD among patients in Sub-Saharan Africa are sparse. We evaluated how MBD relates to breast cancer characteristics in Kenyan women undergoing diagnostic mammography. Methods. This cross-sectional study included women with pathologically confirmed breast cancers (n=123. Pretreatment mammograms of the unaffected breast were assessed to estimate absolute dense area (cm2, nondense area (cm2, and percent density (PD. Relationships between density measurements and clinical characteristics were evaluated using analysis of covariance. Results. Median PD and dense area were 24.9% and 85.3 cm2. Higher PD and dense area were observed in younger women (P<0.01. Higher dense and nondense areas were observed in obese women (P-trend < 0.01. Estrogen receptor (ER positive patients (73% had higher PD and dense area than ER-negative patients (P≤0.02. Triple negative breast cancer (TNBC patients (17% had lower PD and dense area (P≤0.01 compared with non-TNBCs. No associations were observed between MBD and tumor size and grade. Conclusions. Our findings show discordant relationships between MBD and molecular tumor subtypes to those previously observed in Western populations. The relatively low breast density observed at diagnosis may have important implications for cancer prevention initiatives in Kenya. Subsequent larger studies are needed to confirm these findings.

  7. Nanotechnology-Enabled Optical Molecular Imaging of Breast Cancer

    Science.gov (United States)

    2011-07-01

    quantitatively and dynamically detect molecular markers of breast cancer in vivo without tissue removal or directly after removal in a surgical...hour oshells by c es, the nano ting to a fin ER2- positiv (CHTN) th tinction spect ter of 276 nm sert depicts co microscopy. n was visua rption...conclusively determine the penetration depth of the nanoshells. Additionally, a quantitative difference of the nanoshell signal at the surface of the Her2

  8. Molecular Classification of Lobular Carcinoma of the Breast

    Science.gov (United States)

    Fu, Denggang; Zuo, Qi; Huang, Qi; Su, Li; Ring, Huijun Z.; Ring, Brian Z.

    2017-01-01

    The morphology of breast tumors is complicated and diagnosis can be difficult. We present here a novel diagnostic model which we validate on both array-based and RNA sequencing platforms which reliably distinguishes this tumor type across multiple cohorts. We also examine how this molecular classification predicts sensitivity to common chemotherapeutics in cell-line based assays. A total of 1845 invasive breast cancer cases in six cohorts were collected, split into discovery and validation cohorts, and a classifier was created and compared to pathological diagnosis, grade and survival. In the validation cohorts the concordance of predicted diagnosis with a pathological diagnosis was 92%, and 97% when inconclusively classified cases were excluded. Tumor-derived cell lines were classified with the model as having predominantly ductal or lobular-like molecular physiologies, and sensitivity of these lines to relevant compounds was analyzed. A diagnostic tool can be created that reliably distinguishes lobular from ductal carcinoma and allows the classification of cell lines on the basis of molecular profiles associated with these tumor types. This tool may assist in improved diagnosis and aid in explorations of the response of lobular type breast tumor models to different compounds. PMID:28303886

  9. Comparison of Tc-99m maraciclatide and Tc-99m sestamibi molecular breast imaging in patients with suspected breast cancer.

    Science.gov (United States)

    O'Connor, Michael K; Morrow, Melissa M B; Hunt, Katie N; Boughey, Judy C; Wahner-Roedler, Dietlind L; Conners, Amy Lynn; Rhodes, Deborah J; Hruska, Carrie B

    2017-12-01

    Molecular breast imaging (MBI) performed with 99m Tc sestamibi has been shown to be a valuable technique for the detection of breast cancer. Alternative radiotracers such as 99m Tc maraciclatide may offer improved uptake in breast lesions. The purpose of this study was to compare relative performance of 99m Tc sestamibi and 99m Tc maraciclatide in patients with suspected breast cancer, using a high-resolution dedicated gamma camera for MBI. Women with breast lesions suspicious for malignancy were recruited to undergo two MBI examinations-one with 99m Tc sestamibi and one with 99m Tc maraciclatide. A radiologist interpreted MBI studies in a randomized, blinded fashion to assign an assessment score (1-5) and measured lesion size. Lesion-to-background (L/B) ratio was measured with region-of-interest analysis. Among 39 analyzable patients, 21 malignant tumors were identified in 21 patients. Eighteen of 21 tumors (86%) were seen on 99m Tc sestamibi MBI and 19 of 21 (90%) were seen on 99m Tc maraciclatide MBI (p = 1). Tumor extent measured with both radiopharmaceuticals correlated strongly with pathologic size ( 99m Tc sestamibi, r = 0.84; 99m Tc maraciclatide, r = 0.81). The L/B ratio in detected breast cancers was similar for the two radiopharmaceuticals: 1.55 ± 0.36 (mean ± S.D.) for 99m Tc sestamibi and 1.62 ± 0.37 (mean ± S.D.) for 99m Tc maraciclatide (p = 0.53). No correlation was found between the L/B ratio and molecular subtype for 99m Tc sestamibi (r s  = 0.12, p = 0.63) or 99m Tc maraciclatide (r s  = -0.12, p = 0.64). Of 20 benign lesions, 10 (50%) were seen on 99m Tc sestamibi and 9 of 20 (45%) were seen on 99m Tc maraciclatide images (p = 0.1). The average L/B ratio for benign lesions was 1.34 ±0.40 (mean ±S.D.) for 99m Tc sestamibi and 1.41 ±0.52 (mean ±S.D.) for 99m Tc maraciclatide (p = 0.75). Overall diagnostic performance was similar for both radiopharmaceuticals. AUC from ROC

  10. Imaging features of automated breast volume scanner: Correlation with molecular subtypes of breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, Feng-Yang, E-mail: fyzheng16@fudan.edu.cn [Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai 200032 (China); Shanghai Institute of Medical Imaging, Shanghai 200032 (China); Lu, Qing, E-mail: lu.qing@zs-hospital.sh.cn [Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai 200032 (China); Huang, Bei-Jian, E-mail: huang.beijian@zs-hospital.sh.cn [Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai 200032 (China); Shanghai Institute of Medical Imaging, Shanghai 200032 (China); Xia, Han-Sheng, E-mail: zs12036@126.com [Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai 200032 (China); Yan, Li-Xia, E-mail: dndyanlixia@163.com [Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai 200032 (China); Wang, Xi, E-mail: wang.xi@zs-hospital.sh.cn [Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai 200032 (China); Shanghai Institute of Medical Imaging, Shanghai 200032 (China); Yuan, Wei, E-mail: yuan.wei@zs-hospital.sh.cn [Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai 200032 (China); Wang, Wen-Ping, E-mail: wang.wenping@zs-hospital.sh.cn [Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai 200032 (China); Shanghai Institute of Medical Imaging, Shanghai 200032 (China)

    2017-01-15

    Highlights: • ABVS imaging features have a strong correlation with breast cancer molecular subtypes. • Retraction phenomenon on the coronal planes was the most important predictor for Luminal A and Triple Negative subtypes. • ABVS expand the scope of ultrasound in identifying breast cancer molecular subtypes. - Abstract: Objectives: To investigate the correlation between the imaging features obtained by an automated breast volume scanner (ABVS) and molecular subtypes of breast cancer. Methods: We examined 303 malignant breast tumours by ABVS for specific imaging features and by immunohistochemical analysis to determine the molecular subtype. ABVS imaging features, including retraction phenomenon, shape, margins, echogenicity, post-acoustic features, echogenic halo, and calcifications were analysed by univariate and multivariate logistic regression analyses to determine the significant predictive factors of the molecular subtypes. Results: By univariate logistic regression analysis, the predictive factors of the Luminal-A subtype (n = 128) were retraction phenomenon (odds ratio [OR] = 10.188), post-acoustic shadowing (OR = 5.112), and echogenic halo (OR = 3.263, P < 0.001). The predictive factors of the Human-epidermal-growth-factor-receptor-2-amplified subtype (n = 39) were calcifications (OR = 6.210), absence of retraction phenomenon (OR = 4.375), non-mass lesions (OR = 4.286, P < 0.001), absence of echogenic halo (OR = 3.851, P = 0.035), and post-acoustic enhancement (OR = 3.641, P = 0.008). The predictors for the Triple-Negative subtype (n = 47) were absence of retraction phenomenon (OR = 5.884), post-acoustic enhancement (OR = 5.255, P < 0.001), absence of echogenic halo (OR = 4.138, P = 0.002), and absence of calcifications (OR = 3.363, P = 0.001). Predictors for the Luminal-B subtype (n = 89) had a relatively lower association (OR ≤ 2.328). By multivariate logistic regression analysis, retraction phenomenon was the strongest independent predictor for

  11. Imaging features of automated breast volume scanner: Correlation with molecular subtypes of breast cancer

    International Nuclear Information System (INIS)

    Zheng, Feng-Yang; Lu, Qing; Huang, Bei-Jian; Xia, Han-Sheng; Yan, Li-Xia; Wang, Xi; Yuan, Wei; Wang, Wen-Ping

    2017-01-01

    Highlights: • ABVS imaging features have a strong correlation with breast cancer molecular subtypes. • Retraction phenomenon on the coronal planes was the most important predictor for Luminal A and Triple Negative subtypes. • ABVS expand the scope of ultrasound in identifying breast cancer molecular subtypes. - Abstract: Objectives: To investigate the correlation between the imaging features obtained by an automated breast volume scanner (ABVS) and molecular subtypes of breast cancer. Methods: We examined 303 malignant breast tumours by ABVS for specific imaging features and by immunohistochemical analysis to determine the molecular subtype. ABVS imaging features, including retraction phenomenon, shape, margins, echogenicity, post-acoustic features, echogenic halo, and calcifications were analysed by univariate and multivariate logistic regression analyses to determine the significant predictive factors of the molecular subtypes. Results: By univariate logistic regression analysis, the predictive factors of the Luminal-A subtype (n = 128) were retraction phenomenon (odds ratio [OR] = 10.188), post-acoustic shadowing (OR = 5.112), and echogenic halo (OR = 3.263, P < 0.001). The predictive factors of the Human-epidermal-growth-factor-receptor-2-amplified subtype (n = 39) were calcifications (OR = 6.210), absence of retraction phenomenon (OR = 4.375), non-mass lesions (OR = 4.286, P < 0.001), absence of echogenic halo (OR = 3.851, P = 0.035), and post-acoustic enhancement (OR = 3.641, P = 0.008). The predictors for the Triple-Negative subtype (n = 47) were absence of retraction phenomenon (OR = 5.884), post-acoustic enhancement (OR = 5.255, P < 0.001), absence of echogenic halo (OR = 4.138, P = 0.002), and absence of calcifications (OR = 3.363, P = 0.001). Predictors for the Luminal-B subtype (n = 89) had a relatively lower association (OR ≤ 2.328). By multivariate logistic regression analysis, retraction phenomenon was the strongest independent predictor for

  12. Molecular imaging: High-resolution detectors for early diagnosis and therapy monitoring of breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Garibaldi, F. [Istituto Superiore di Sanita and INFN-gr. Sanita-Rome (Italy)]. E-mail: Franco.garibaldi@iss.infn.it; Cisbani, E. [Istituto Superiore di Sanita and INFN-gr. Sanita-Rome (Italy); Colilli, S. [Istituto Superiore di Sanita and INFN-gr. Sanita-Rome (Italy); Cusanno, F. [Istituto Superiore di Sanita and INFN-gr. Sanita-Rome (Italy); Fratoni, R. [Istituto Superiore di Sanita and INFN-gr. Sanita-Rome (Italy); Giuliani, F. [Istituto Superiore di Sanita and INFN-gr. Sanita-Rome (Italy); Gricia, M. [Istituto Superiore di Sanita and INFN-gr. Sanita-Rome (Italy); Lucentini, M. [Istituto Superiore di Sanita and INFN-gr. Sanita-Rome (Italy); Fratoni, R. [Istituto Superiore di Sanita and INFN-gr. Sanita-Rome (Italy); Lo Meo, S. [Istituto Superiore di Sanita and INFN-gr. Sanita-Rome (Italy); Magliozzi, M.L. [Istituto Superiore di Sanita and INFN-gr. Sanita-Rome (Italy); Santanvenere, F. [Istituto Superiore di Sanita and INFN-gr. Sanita-Rome (Italy); Cinti, M.N. [University La Sapienza, Rome (Italy); Pani, R. [University La Sapienza, Rome (Italy); Pellegrini, R. [University La Sapienza, Rome (Italy); Simonetti, G. [University Tor Vergata, Rome (Italy); Schillaci, O. [University Tor Vergata, Rome (Italy); Del Vecchio, S. [CNR Napoli, Naples (Italy); Salvatore, M. [CNR Napoli, Naples (Italy); Majewski, S. [Jefferson Lab, Newport News, VA (United States); Lanza, R.C. [Massachusetts Institute of Technology, Cambridge, MA (United States); De Vincentis, G. [University La Sapienza, Rome (Italy); Scopinaro, F. [University La Sapienza, Rome (Italy)

    2006-12-20

    Dedicated high-resolution detectors are required for detection of small cancerous breast tumours by molecular imaging with radionuclides. Absorptive collimation is normally applied in imaging single photon emitters, but it results in a strong reduction in detection efficiency. Systems based on electronic collimation are complex and expensive. For these reasons simulations and measurements have been performed to design optimised dedicated high-resolution mini gamma camera. Critical parameters are contrast and signal-to-noise ratio (SNR). Intrinsic performance (spatial resolution, pixel identification, and response linearity and uniformity) were first optimised. Pixellated scintillator arrays (NaI(Tl)) of different pixel size were coupled to arrays of PSPMTs with different anode pad dimensions (6x6 mm{sup 2} and 3x3 mm{sup 2}). Detectors having a field of view (FOV) of 100x100 mm{sup 2} and 150x200 mm{sup 2} were designed and built. The electronic system allows read out of all the anode pad signals. The collimation technique was then considered and limits of coded aperture option were studied. Preliminary results are presented.

  13. Implementation and analysis of list mode algorithm using tubes of response on a dedicated brain and breast PET

    Science.gov (United States)

    Moliner, L.; Correcher, C.; González, A. J.; Conde, P.; Hernández, L.; Orero, A.; Rodríguez-Álvarez, M. J.; Sánchez, F.; Soriano, A.; Vidal, L. F.; Benlloch, J. M.

    2013-02-01

    In this work we present an innovative algorithm for the reconstruction of PET images based on the List-Mode (LM) technique which improves their spatial resolution compared to results obtained with current MLEM algorithms. This study appears as a part of a large project with the aim of improving diagnosis in early Alzheimer disease stages by means of a newly developed hybrid PET-MR insert. At the present, Alzheimer is the most relevant neurodegenerative disease and the best way to apply an effective treatment is its early diagnosis. The PET device will consist of several monolithic LYSO crystals coupled to SiPM detectors. Monolithic crystals can reduce scanner costs with the advantage to enable implementation of very small virtual pixels in their geometry. This is especially useful for LM reconstruction algorithms, since they do not need a pre-calculated system matrix. We have developed an LM algorithm which has been initially tested with a large aperture (186 mm) breast PET system. Such an algorithm instead of using the common lines of response, incorporates a novel calculation of tubes of response. The new approach improves the volumetric spatial resolution about a factor 2 at the border of the field of view when compared with traditionally used MLEM algorithm. Moreover, it has also shown to decrease the image noise, thus increasing the image quality.

  14. Implementation and analysis of list mode algorithm using tubes of response on a dedicated brain and breast PET

    International Nuclear Information System (INIS)

    Moliner, L.; Correcher, C.; González, A.J.; Conde, P.; Hernández, L.; Orero, A.; Rodríguez-Álvarez, M.J.; Sánchez, F.; Soriano, A.; Vidal, L.F.; Benlloch, J.M.

    2013-01-01

    In this work we present an innovative algorithm for the reconstruction of PET images based on the List-Mode (LM) technique which improves their spatial resolution compared to results obtained with current MLEM algorithms. This study appears as a part of a large project with the aim of improving diagnosis in early Alzheimer disease stages by means of a newly developed hybrid PET-MR insert. At the present, Alzheimer is the most relevant neurodegenerative disease and the best way to apply an effective treatment is its early diagnosis. The PET device will consist of several monolithic LYSO crystals coupled to SiPM detectors. Monolithic crystals can reduce scanner costs with the advantage to enable implementation of very small virtual pixels in their geometry. This is especially useful for LM reconstruction algorithms, since they do not need a pre-calculated system matrix. We have developed an LM algorithm which has been initially tested with a large aperture (186 mm) breast PET system. Such an algorithm instead of using the common lines of response, incorporates a novel calculation of tubes of response. The new approach improves the volumetric spatial resolution about a factor 2 at the border of the field of view when compared with traditionally used MLEM algorithm. Moreover, it has also shown to decrease the image noise, thus increasing the image quality

  15. Molecular Mechanisms of Anticancer Effects of Phytoestrogens in Breast Cancer.

    Science.gov (United States)

    Hsieh, Chia-Jung; Hsu, Ya-Ling; Huang, Ya-Fang; Tsai, Eing-Mei

    2018-01-01

    Phytoestrogens derived from plants exert estrogenic as well as antiestrogenic effects and multiple actions within breast cancer cells. Chemopreventive properties of phytoestrogens have emerged from epidemiological observations. In recent clinical research studies, phytoestrogens are safe and may even protect against breast cancer. In this brief review, the molecular mechanisms of phytoestrogens on regulation of cell cycle, apoptosis, estrogen receptors, cell signaling pathways, and epigenetic modulations in relation to breast cancer are discussed. Phytoestrogens have a preferential affinity for estrogen receptor (ER)-β, which appears to be associated with antiproliferative and anticarcinogenic effects. Moreover, while phytoestrogens not only inhibit ER-positive but also ER-negative breast cancer cells, the possibility of epigenetic modulation playing an important role is also discussed. In conclusion, as there are multiple targets and actions of phytoestrogens, extensive research is still necessary. However, due to low toxicity, low cost, and easy availability, their potent chemoprevention effects deserve further study. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  16. Comprehensive Molecular Portraits of Invasive Lobular Breast Cancer.

    Science.gov (United States)

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

    2015-10-08

    Invasive lobular carcinoma (ILC) is the second most prevalent histologic subtype of invasive breast cancer. Here, we comprehensively profiled 817 breast tumors, including 127 ILC, 490 ductal (IDC), and 88 mixed IDC/ILC. Besides E-cadherin loss, the best known ILC genetic hallmark, we identified mutations targeting PTEN, TBX3, and FOXA1 as ILC enriched features. PTEN loss associated with increased AKT phosphorylation, which was highest in ILC among all breast cancer subtypes. Spatially clustered FOXA1 mutations correlated with increased FOXA1 expression and activity. Conversely, GATA3 mutations and high expression characterized luminal A IDC, suggesting differential modulation of ER activity in ILC and IDC. Proliferation and immune-related signatures determined three ILC transcriptional subtypes associated with survival differences. Mixed IDC/ILC cases were molecularly classified as ILC-like and IDC-like revealing no true hybrid features. This multidimensional molecular atlas sheds new light on the genetic bases of ILC and provides potential clinical options. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Molecular subtypes and imaging phenotypes of breast cancer

    International Nuclear Information System (INIS)

    Cho, Nariya

    2016-01-01

    During the last 15 years, traditional breast cancer classifications based on histopathology have been reorganized into the luminal A, luminal B, human epidermal growth factor receptor 2 (HER2), and basal-like subtypes based on gene expression profiling. Each molecular subtype has shown varying risk for progression, response to treatment, and survival outcomes. Research linking the imaging phenotype with the molecular subtype has revealed that non-calcified, relatively circumscribed masses with posterior acoustic enhancement are common in the basal-like subtype, spiculated masses with a poorly circumscribed margin and posterior acoustic shadowing in the luminal subtype, and pleomorphic calcifications in the HER2-enriched subtype. Understanding the clinical implications of the molecular subtypes and imaging phenotypes could help radiologists guide precision medicine, tailoring medical treatment to patients and their tumor characteristics

  18. Molecular subtypes and imaging phenotypes of breast cancer

    Directory of Open Access Journals (Sweden)

    Nariya Cho

    2016-10-01

    Full Text Available During the last 15 years, traditional breast cancer classifications based on histopathology have been reorganized into the luminal A, luminal B, human epidermal growth factor receptor 2 (HER2, and basal-like subtypes based on gene expression profiling. Each molecular subtype has shown varying risk for progression, response to treatment, and survival outcomes. Research linking the imaging phenotype with the molecular subtype has revealed that non-calcified, relatively circumscribed masses with posterior acoustic enhancement are common in the basal-like subtype, spiculated masses with a poorly circumscribed margin and posterior acoustic shadowing in the luminal subtype, and pleomorphic calcifications in the HER2-enriched subtype. Understanding the clinical implications of the molecular subtypes and imaging phenotypes could help radiologists guide precision medicine, tailoring medical treatment to patients and their tumor characteristics.

  19. Molecular subtypes and imaging phenotypes of breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Nariya [Dept. of Radiology, Seoul National University Hospital, Seoul (Korea, Republic of)

    2016-08-15

    During the last 15 years, traditional breast cancer classifications based on histopathology have been reorganized into the luminal A, luminal B, human epidermal growth factor receptor 2 (HER2), and basal-like subtypes based on gene expression profiling. Each molecular subtype has shown varying risk for progression, response to treatment, and survival outcomes. Research linking the imaging phenotype with the molecular subtype has revealed that non-calcified, relatively circumscribed masses with posterior acoustic enhancement are common in the basal-like subtype, spiculated masses with a poorly circumscribed margin and posterior acoustic shadowing in the luminal subtype, and pleomorphic calcifications in the HER2-enriched subtype. Understanding the clinical implications of the molecular subtypes and imaging phenotypes could help radiologists guide precision medicine, tailoring medical treatment to patients and their tumor characteristics.

  20. [Molecular characterization of breast cancer in clinical practice].

    Science.gov (United States)

    Zemmouri, Y; De Croze, D; Vincent Salomon, A; Rouzier, R; Bonneau, C

    2016-05-01

    Breast cancer involves various types of tumors. The objective of this review was to provide a summary of the main methods currently available in clinical practice to characterize breast cancers at a molecular level and to discuss their prognostic and predictive values. Hormonal receptors expression and the HER2 status are prognostic markers and can also predict the response to targeted therapies. Their analysis through immunohistochemistry is systematical. Ki67 is an effective prognostic marker, but its reliability is debated because of its low reproducibility between laboratories and between pathologists. Commercial genomic signatures are all considered valid prognostic tools and may guide physicians to make therapeutic choices. These signatures are costly and should therefore be restricted to situations in which the use of chemotherapy remains equivocal. Copyright © 2016. Published by Elsevier SAS.

  1. Breast Conservation Therapy: The Influence of Molecular Subtype and Margins

    International Nuclear Information System (INIS)

    Demirci, Senem; Broadwater, Gloria; Marks, Lawrence B.; Clough, Robert; Prosnitz, Leonard R.

    2012-01-01

    Purpose: To evaluate treatment results and prognostic factors, especially margin status and molecular subtype, in early-stage breast cancer patients treated with breast conservation therapy (BCT). Methods and Materials: The records of 1,058 Stage I or II breast cancer patients treated with BCT (surgical excision plus radiotherapy) at Duke University Medical Center, Durham, North Carolina, from 1985–2005 were retrospectively reviewed. Conventional receptor analyses were used as surrogate markers for molecular subtype classification (luminal A, luminal B, Her2 positive, and basal like). Actuarial estimates of overall survival (OS), cause-specific survival (CSS), failure-free survival, and locoregional control (LRC) were computed by use of Kaplan-Meier plots. We analyzed prognostic variables for significance using Cox proportional hazards univariate and multivariate analysis. The study was approved by the Duke University Medical Center Institutional Review Board. Results: The median age of the patients was 56 years (range, 18–89 years). Of the patients, 80% had T1 disease and 66% N0 disease pathologically. With a median follow-up of 9.8 years, an in-breast recurrence developed in 53 patients and 10 patients had nodal failure. For all patients, the 10-year CSS rate was 94%; LRC rate, 94%; and failure-free survival rate, 88%. Luminal A patients had a CSS rate of 95% and LRC rate of 99%. Basal-type patients appeared to do worse, with regard to both CSS rate (74%) and LRC rate (76%), but the numbers were small and the difference was not statistically significant. LRC rates of patients with negative margins (widely negative, close, and extent of margin not known) were virtually identical (93%, 96%, and 94%, respectively). Those with positive margins appeared to fare slightly worse based on LRC rate (88%), but again, the numbers were small and the difference was not statistically significant. Conclusions: BCT remains the treatment of choice for early-stage breast cancer

  2. Breast Conservation Therapy: The Influence of Molecular Subtype and Margins

    Energy Technology Data Exchange (ETDEWEB)

    Demirci, Senem, E-mail: senem.demirci@ege.edu.tr [Department of Radiation Oncology, Duke University Medical Center, Durham, NC (United States); Department of Radiation Oncology, Ege University Faculty of Medicine, Izmir (Turkey); Broadwater, Gloria [Department of Biostatistics and Bioinformatics, Duke Cancer Institute, Durham, NC (United States); Cancer and Leukemia Group B Statistical Center, Duke Cancer Institute, Durham, NC (United States); Marks, Lawrence B. [Department of Radiation Oncology, University of North Carolina School of Medicine, Chapel Hill, NC (United States); Clough, Robert; Prosnitz, Leonard R. [Department of Radiation Oncology, Duke University Medical Center, Durham, NC (United States)

    2012-07-01

    Purpose: To evaluate treatment results and prognostic factors, especially margin status and molecular subtype, in early-stage breast cancer patients treated with breast conservation therapy (BCT). Methods and Materials: The records of 1,058 Stage I or II breast cancer patients treated with BCT (surgical excision plus radiotherapy) at Duke University Medical Center, Durham, North Carolina, from 1985-2005 were retrospectively reviewed. Conventional receptor analyses were used as surrogate markers for molecular subtype classification (luminal A, luminal B, Her2 positive, and basal like). Actuarial estimates of overall survival (OS), cause-specific survival (CSS), failure-free survival, and locoregional control (LRC) were computed by use of Kaplan-Meier plots. We analyzed prognostic variables for significance using Cox proportional hazards univariate and multivariate analysis. The study was approved by the Duke University Medical Center Institutional Review Board. Results: The median age of the patients was 56 years (range, 18-89 years). Of the patients, 80% had T1 disease and 66% N0 disease pathologically. With a median follow-up of 9.8 years, an in-breast recurrence developed in 53 patients and 10 patients had nodal failure. For all patients, the 10-year CSS rate was 94%; LRC rate, 94%; and failure-free survival rate, 88%. Luminal A patients had a CSS rate of 95% and LRC rate of 99%. Basal-type patients appeared to do worse, with regard to both CSS rate (74%) and LRC rate (76%), but the numbers were small and the difference was not statistically significant. LRC rates of patients with negative margins (widely negative, close, and extent of margin not known) were virtually identical (93%, 96%, and 94%, respectively). Those with positive margins appeared to fare slightly worse based on LRC rate (88%), but again, the numbers were small and the difference was not statistically significant. Conclusions: BCT remains the treatment of choice for early-stage breast cancer

  3. Molecular Imaging of Breast Cancer: Present and future directions

    Directory of Open Access Journals (Sweden)

    David eAlcantara

    2014-12-01

    Full Text Available Medical imaging technologies have undergone explosive growth over the past few decades and now play a central role in clinical oncology. But the truly transformative power of imaging in the clinical management of cancer patients lies ahead. Today, imaging is at a crossroads, with molecularly targeted imaging agents expected to broadly expand the capabilities of conventional anatomical imaging methods. Molecular imaging will allow clinicians to not only see where a tumour is located in the body, but also to visualize the expression and activity of specific molecules (e.g. proteases and protein kinases and biological processes (e.g. apoptosis, angiogenesis, and metastasis that influence tumour behavior and/or response to therapy. Breast cancer, the most common cancer among women and a research area where our group is actively involved, is a very heterogeneous disease with diverse patterns of development and response to treatment. Hence, molecular imaging is expected to have a major impact on this type of cancer, leading to important improvements in diagnosis, individualized treatment, and drug development, as well as our understanding of how breast cancer arises.

  4. Molecular Characterization of ERα-positive and Triple Negative Breast Cancer

    NARCIS (Netherlands)

    Severson, T.M.

    2016-01-01

    Breast cancer, one of the most common of all cancers, is diagnosed in over 1.5 million people world-wide each year. Overall, treatments for breast cancer are considered relatively successful, however recurrence is a clinical problem of paramount importance. Molecular subtypes of breast cancer,

  5. Breast cancer molecular subtype classifier that incorporates MRI features.

    Science.gov (United States)

    Sutton, Elizabeth J; Dashevsky, Brittany Z; Oh, Jung Hun; Veeraraghavan, Harini; Apte, Aditya P; Thakur, Sunitha B; Morris, Elizabeth A; Deasy, Joseph O

    2016-07-01

    To use features extracted from magnetic resonance (MR) images and a machine-learning method to assist in differentiating breast cancer molecular subtypes. This retrospective Health Insurance Portability and Accountability Act (HIPAA)-compliant study received Institutional Review Board (IRB) approval. We identified 178 breast cancer patients between 2006-2011 with: 1) ERPR + (n = 95, 53.4%), ERPR-/HER2 + (n = 35, 19.6%), or triple negative (TN, n = 48, 27.0%) invasive ductal carcinoma (IDC), and 2) preoperative breast MRI at 1.5T or 3.0T. Shape, texture, and histogram-based features were extracted from each tumor contoured on pre- and three postcontrast MR images using in-house software. Clinical and pathologic features were also collected. Machine-learning-based (support vector machines) models were used to identify significant imaging features and to build models that predict IDC subtype. Leave-one-out cross-validation (LOOCV) was used to avoid model overfitting. Statistical significance was determined using the Kruskal-Wallis test. Each support vector machine fit in the LOOCV process generated a model with varying features. Eleven out of the top 20 ranked features were significantly different between IDC subtypes with P machine-learning-based predictive model using features extracted from MRI that can distinguish IDC subtypes with significant predictive power. J. Magn. Reson. Imaging 2016;44:122-129. © 2016 Wiley Periodicals, Inc.

  6. Added value of dedicated axillary hybrid 18F-FDG PET/MRI for improved axillary nodal staging in clinically node-positive breast cancer patients. A feasibility study

    International Nuclear Information System (INIS)

    Nijnatten, Thiemo J.A. van; Goorts, B.; Voeoe, S.; Wildberger, J.E.; Boer, M. de; Kooreman, L.F.S.; Heuts, E.M.; Mottaghy, F.M.; Lobbes, M.B.I.; Smidt, M.L.

    2018-01-01

    To investigate the feasibility and potential added value of dedicated axillary 18F-FDG hybrid PET/MRI, compared to standard imaging modalities (i.e. ultrasound [US], MRI and PET/CT), for axillary nodal staging in clinically node-positive breast cancer. Twelve patients with clinically node-positive breast cancer underwent axillary US and dedicated axillary hybrid 18F-FDG PET/MRI. Nine of the 12 patients also underwent whole-body PET/CT. Maximum standardized uptake values (SUVmax) were measured for the primary breast tumor and the most FDG-avid axillary lymph node. A positive axillary lymph node on dedicated axillary hybrid PET/MRI was defined as a moderate to very intense FDG-avid lymph node. The diagnostic performance of dedicated axillary hybrid PET/MRI was calculated by comparing quantitative and its qualitative measurements to results of axillary US, MRI and PET/CT. The number of suspicious axillary lymph nodes was subdivided as follows: N0 (0 nodes), N1 (1-3 nodes), N2 (4-9 nodes) and N3 (≥ 10 nodes). According to dedicated axillary hybrid PET/MRI findings, seven patients were diagnosed with N1, four with N2 and one with N3. With regard to mean SUVmax, there was no significant difference in the primary tumor (9.0 [±5.0] vs. 8.6 [±5.7], p = 0.678) or the most FDG-avid axillary lymph node (7.8 [±5.3] vs. 7.7 [±4.3], p = 0.767) between dedicated axillary PET/MRI and PET/CT. Compared to standard imaging modalities, dedicated axillary hybrid PET/MRI resulted in changes in nodal status as follows: 40% compared to US, 75% compared to T2-weighted MRI, 40% compared to contrast-enhanced MRI, and 22% compared to PET/CT. Adding dedicated axillary 18F-FDG hybrid PET/MRI to diagnostic work-up may improve the diagnostic performance of axillary nodal staging in clinically node-positive breast cancer patients. (orig.)

  7. Added value of dedicated axillary hybrid 18F-FDG PET/MRI for improved axillary nodal staging in clinically node-positive breast cancer patients. A feasibility study

    Energy Technology Data Exchange (ETDEWEB)

    Nijnatten, Thiemo J.A. van; Goorts, B. [Maastricht University Medical Center+, Department of Radiology and Nuclear Medicine (Netherlands); Maastricht University Medical Center+, Department of Surgery, Maastricht (Netherlands); Maastricht University Medical Center+, GROW - School for Oncology and Developmental Biology, Maastricht (Netherlands); Voeoe, S.; Wildberger, J.E. [Maastricht University Medical Center+, Department of Radiology and Nuclear Medicine (Netherlands); Boer, M. de [Maastricht University Medical Center+, GROW - School for Oncology and Developmental Biology, Maastricht (Netherlands); Maastricht University Medical Center+, Division of Internal Medicine, Department of Medical Oncology, Maastricht (Netherlands); Kooreman, L.F.S. [Maastricht University Medical Center+, GROW - School for Oncology and Developmental Biology, Maastricht (Netherlands); Maastricht University Medical Center+, Department of Pathology, Maastricht (Netherlands); Heuts, E.M. [Maastricht University Medical Center+, Department of Surgery, Maastricht (Netherlands); Mottaghy, F.M. [Maastricht University Medical Center+, Department of Radiology and Nuclear Medicine (Netherlands); RWTH Aachen University, Department of Nuclear Medicine, University Hospital, Aachen (Germany); Lobbes, M.B.I. [Maastricht University Medical Center+, Department of Radiology and Nuclear Medicine (Netherlands); Maastricht University Medical Center+, GROW - School for Oncology and Developmental Biology, Maastricht (Netherlands); Smidt, M.L. [Maastricht University Medical Center+, Department of Surgery, Maastricht (Netherlands); Maastricht University Medical Center+, GROW - School for Oncology and Developmental Biology, Maastricht (Netherlands)

    2018-02-15

    To investigate the feasibility and potential added value of dedicated axillary 18F-FDG hybrid PET/MRI, compared to standard imaging modalities (i.e. ultrasound [US], MRI and PET/CT), for axillary nodal staging in clinically node-positive breast cancer. Twelve patients with clinically node-positive breast cancer underwent axillary US and dedicated axillary hybrid 18F-FDG PET/MRI. Nine of the 12 patients also underwent whole-body PET/CT. Maximum standardized uptake values (SUVmax) were measured for the primary breast tumor and the most FDG-avid axillary lymph node. A positive axillary lymph node on dedicated axillary hybrid PET/MRI was defined as a moderate to very intense FDG-avid lymph node. The diagnostic performance of dedicated axillary hybrid PET/MRI was calculated by comparing quantitative and its qualitative measurements to results of axillary US, MRI and PET/CT. The number of suspicious axillary lymph nodes was subdivided as follows: N0 (0 nodes), N1 (1-3 nodes), N2 (4-9 nodes) and N3 (≥ 10 nodes). According to dedicated axillary hybrid PET/MRI findings, seven patients were diagnosed with N1, four with N2 and one with N3. With regard to mean SUVmax, there was no significant difference in the primary tumor (9.0 [±5.0] vs. 8.6 [±5.7], p = 0.678) or the most FDG-avid axillary lymph node (7.8 [±5.3] vs. 7.7 [±4.3], p = 0.767) between dedicated axillary PET/MRI and PET/CT. Compared to standard imaging modalities, dedicated axillary hybrid PET/MRI resulted in changes in nodal status as follows: 40% compared to US, 75% compared to T2-weighted MRI, 40% compared to contrast-enhanced MRI, and 22% compared to PET/CT. Adding dedicated axillary 18F-FDG hybrid PET/MRI to diagnostic work-up may improve the diagnostic performance of axillary nodal staging in clinically node-positive breast cancer patients. (orig.)

  8. Molecular Characterization and Mortality From Breast Cancer in Men.

    Science.gov (United States)

    Massarweh, Suleiman Alfred; Sledge, George W; Miller, Dave P; McCullough, Debbie; Petkov, Valentina I; Shak, Steven

    2018-05-10

    Purpose Limited data exist on the molecular biology, treatment, and outcomes of breast cancer in men, and much of our understanding in this area remains largely an extrapolation from data in women with breast cancer. Materials and Methods We studied men and women with hormone receptor-positive breast cancer and the 21-gene Breast Recurrence Score (RS) results. Differences in clinical characteristics and gene expression were determined, and distribution of RS results was correlated with 5-year breast cancer-specific survival (BCSS) and overall survival. Results There were 3,806 men and 571,115 women. Men were older than women (mean age, 64.2 v 59.1 years; P < .001). RS < 18 predominated in both genders, but RS ≥ 31 was more frequent in men (12.4% v 7.4%; P < .001), as were very low scores (RS < 11; 33.8% v 22.1%; P < .001). Mean gene expression was higher in men for the estrogen receptor (ER), proliferation, and invasion groups. ER was lowest and progesterone receptor was highest in women younger than 50 years of age, with a progressive increase in ER with age. Men younger than 50 years of age had slightly lower ER and progesterone receptor compared with older men. Survival data were available from SEER for 322 men and 55,842 women. Five-year BCSS was 99.0% (95% CI, 99.3% to 99.9%) and 95.9% (95% CI, 87.6% to 98.7%) for men with RS < 18 and RS 18-30, respectively, and for women, it was 99.5% (95% CI, 99.4% to 99.6%) and 98.6% (95% CI, 98.4% to 98.8%), respectively. RS ≥ 31 was associated with an 81.0% 5-year BCSS in men (95% CI, 53.3% to 93.2%) and 94.9% 5-year BCSS (95% CI, 93.9% to 95.7%) in women. Five-year BCSS and overall survival were lower in men than in women. Conclusion This study reveals some distinctive biologic features of breast cancer in men and an important prognostic role for RS testing in both men and women.

  9. Validation of a Radiosensitivity Molecular Signature in Breast Cancer

    Science.gov (United States)

    Eschrich, Steven A.; Fulp, William J.; Pawitan, Yudi; Foekens, John A.; Smid, Marcel; Martens, John W. M.; Echevarria, Michelle; Kamath, Vidya; Lee, Ji-Hyun; Harris, Eleanor E.; Bergh, Jonas; Torres-Roca, Javier F.

    2014-01-01

    Purpose Previously, we developed a radiosensitivity molecular signature (RSI) that was clinically-validated in three independent datasets (rectal, esophageal, head and neck) in 118 patients. Here, we test RSI in radiotherapy (RT) treated breast cancer patients. Experimental Design RSI was tested in two previously published breast cancer datasets. Patients were treated at the Karolinska University Hospital (n=159) and Erasmus Medical Center (n=344). RSI was applied as previously described. Results We tested RSI in RT-treated patients (Karolinska). Patients predicted to be radiosensitive (RS) had an improved 5 yr relapse-free survival when compared with radioresistant (RR) patients (95% vs. 75%, p=0.0212) but there was no difference between RS/RR patients treated without RT (71% vs. 77%, p=0.6744), consistent with RSI being RT-specific (interaction term RSIxRT, p=0.05). Similarly, in the Erasmus dataset RT-treated RS patients had an improved 5-year distant-metastasis-free survival over RR patients (77% vs. 64%, p=0.0409) but no difference was observed in patients treated without RT (RS vs. RR, 80% vs. 81%, p=0.9425). Multivariable analysis showed RSI is the strongest variable in RT-treated patients (Karolinska, HR=5.53, p=0.0987, Erasmus, HR=1.64, p=0.0758) and in backward selection (removal alpha of 0.10) RSI was the only variable remaining in the final model. Finally, RSI is an independent predictor of outcome in RT-treated ER+ patients (Erasmus, multivariable analysis, HR=2.64, p=0.0085). Conclusions RSI is validated in two independent breast cancer datasets totaling 503 patients. Including prior data, RSI is validated in five independent cohorts (621 patients) and represents, to our knowledge, the most extensively validated molecular signature in radiation oncology. PMID:22832933

  10. Bioanalytics of mycotoxins and development of dedicated analyte-selective molecularly imprinted materials for solid-phase extraction

    International Nuclear Information System (INIS)

    Jodlbauer, H.J.

    2001-09-01

    Mycotoxins are secondary metabolites produced by several fungal species, growing on agricultural products during cultivation, harvest, transport or storage. Ochratoxin A (OTA) is a mycotoxin of great natural abundance and can be found in various plant products. Due to its frequent occurrence and toxic properties many countries have set up tolerance levels for OTA. Thus, the need for sensitive analytical and in particular selective sample preparation methods for analyte enrichment and removal of interfering matrix compounds is obvious. Molecular imprinting generates polymeric matrices that can selectively recognize and bind target molecules. It was previously demonstrated that molecularly imprinted polymers (MIPs) can be employed in sample preparation. MIPs capable of recognizing OTA have been prepared using an analyte mimic approach. Crucial to the success was the introduction of a novel class of quinuclidine-derived functional monomers which utilize ionic binding increments and hydrophobic interactions for selective recognition of the target analyte and its mimics. Since optimization of SPE procedures demonstrated the convenient use of several solvent systems, the developed MIPs represents an enrichment for the field of mycotoxin analysis. Zeranol has been widely adopted as a growth stimulant for cattle and other animals due to its anabolic and estrogenic properties. Application of zeranol has been banned in the European Union since 1985. Researchers, however, found that the illegal administration of this anabolic agent may not be the only source of zeranol residues in biologically relevant matrices. Previously, it was demonstrated that zeranol was also formed in vivo from the mycotoxins zearalenone (ZON) and α-zearalenol that are carried over from mycotoxin contaminated feed into the animal body. A fast, robust and sensitive LC-MS method for the determination for these compounds in urine and tissue samples has been developed. Crucial for the achievement of low

  11. Multiparametric and molecular imaging of breast tumors with MRI and PET/MRI

    International Nuclear Information System (INIS)

    Pinker, K.; Marino, M.A.; Meyer-Baese, A.; Helbich, T.H.

    2016-01-01

    Magnetic resonance imaging (MRI) of the breast is an indispensable tool in breast imaging for many indications. Several functional parameters with MRI and positron emission tomography (PET) have been assessed for imaging of breast tumors and their combined application is defined as multiparametric imaging. Available data suggest that multiparametric imaging using different functional MRI and PET parameters can provide detailed information about the hallmarks of cancer and may provide additional specificity. Multiparametric and molecular imaging of the breast comprises established MRI parameters, such as dynamic contrast-enhanced MRI, diffusion-weighted imaging (DWI), MR proton spectroscopy ( 1 H-MRSI) as well as combinations of radiological and MRI techniques (e.g. PET/CT and PET/MRI) using radiotracers, such as fluorodeoxyglucose (FDG). Multiparametric and molecular imaging of the breast can be performed at different field-strengths (range 1.5-7 T). Emerging parameters comprise novel promising techniques, such as sodium imaging ( 23 Na MRI), phosphorus spectroscopy ( 31 P-MRSI), chemical exchange saturation transfer (CEST) imaging, blood oxygen level-dependent (BOLD) and hyperpolarized MRI as well as various specific radiotracers. Multiparametric and molecular imaging has multiple applications in breast imaging. Multiparametric and molecular imaging of the breast is an evolving field that will enable improved detection, characterization, staging and monitoring for personalized medicine in breast cancer. (orig.) [de

  12. Molecular markers in breast cancer: new tools in imaging and prognosis

    NARCIS (Netherlands)

    Vermeulen, J.F.

    2012-01-01

    Breast cancer is the most frequently diagnosed cancer in women. Although breast cancer is mainly diagnosed by mammography, other imaging modalities (e.g. MRI, PET) are increasingly used. The most recent developments in the field of molecular imaging comprise the application of near-infrared

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

    Science.gov (United States)

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

    2015-09-01

    The purposes of this study were to compare the tumor appearance of invasive breast cancer on direct-conversion molecular breast imaging using a standardized lexicon and to determine how often direct-conversion molecular breast imaging identifies all known invasive tumor foci in the breast, and whether this differs for invasive ductal versus lobular histologic profiles. Patients with prior invasive breast cancer and concurrent direct-conversion molecular breast imaging examinations were retrospectively reviewed. Blinded review of direct-conversion molecular breast imaging examinations was performed by one of two radiologists, according to a validated lexicon. Direct-conversion molecular breast imaging findings were matched with lesions described on the pathology report to exclude benign reasons for direct-conversion molecular breast imaging findings and to document direct-conversion molecular breast imaging-occult tumor foci. Associations between direct-conversion molecular breast imaging findings and tumor histologic profiles were examined using chi-square tests. In 286 patients, 390 invasive tumor foci were present in 294 breasts. A corresponding direct-conversion molecular breast imaging finding was present for 341 of 390 (87%) tumor foci described on the pathology report. Invasive ductal carcinoma (IDC) tumor foci were more likely to be a mass (40% IDC vs 15% invasive lobular carcinoma [ILC]; p < 0.001) and to have marked intensity than were ILC foci (63% IDC vs 32% ILC; p < 0.001). Direct-conversion molecular breast imaging correctly revealed all pathology-proven foci of 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 < 0.0001). Overall, direct-conversion molecular breast imaging showed all known 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

  14. Association Between Imaging Characteristics and Different Molecular Subtypes of Breast Cancer.

    Science.gov (United States)

    Wu, Mingxiang; Ma, Jie

    2017-04-01

    Breast cancer can be divided into four major molecular subtypes based on the expression of hormone receptor (estrogen receptor and progesterone receptor), human epidermal growth factor receptor 2, HER2 status, and molecular proliferation rate (Ki67). In this study, we sought to investigate the association between breast cancer subtype and radiological findings in the Chinese population. Medical records of 300 consecutive invasive breast cancer patients were reviewed from the database: the Breast Imaging Reporting and Data System. The imaging characteristics of the lesions were evaluated. The molecular subtypes of breast cancer were classified into four types: luminal A, luminal B, HER2 overexpressed (HER2), and basal-like breast cancer (BLBC). Univariate and multivariate logistic regression analyses were performed to assess the association between the subtype (dependent variable) and mammography or 15 magnetic resonance imaging (MRI) indicators (independent variables). Luminal A and B subtypes were commonly associated with "clustered calcification distribution," "nipple invasion," or "skin invasion" (P cancers showed association with persistent enhancement in the delayed phase on MRI and "clustered calcification distribution" on mammography (P breast tumor, which are potentially useful tools in the diagnosis and subtyping of breast cancer. Copyright © 2017 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

  15. Correlativity study on MRI morphologic features, pathology, and molecular biology of breast cancer

    International Nuclear Information System (INIS)

    Chen Rong; Gong Shuigen; Zhang Weiguo; Chen Jinhua; He Shuangwu; Liu Baohua; Li Zengpeng

    2004-01-01

    Objective: To investigate the correlation among MRI morphologic features, pathology, and molecular biology of breast cancer. Methods: MR scanning was performed in 78 patients with breast cancer before operation and MRI morphologic features of breast cancer were analyzed. The mastectomy specimens of the breast neoplasm were stained with immunohistochemistry, and the expression of estrogen receptor (ER), progesterone receptor (PR), C-erbB-2, p53, and the distribution of microvessel density (MVD) was measured. The pathologic results were compared with MRI features. Results: Among the 80 breast cancers, ER positive expression was positively correlated with the spiculate margin of breast cancer (P 0.05). Among the 41 breast cancers with dynamic MR scans, there was positive correlation between the spatial distribution of contrast agent and MVD (P<0.01). Conclusion: There exists some correlation among MRI morphologic features, pathology, and molecular biology factors in breast cancer to certain extent. The biologic behavior and prognosis of the breast cancer can be assessed according to MRI features

  16. Treatment outcome in patients with triple negative early stage breast cancers compared with other molecular subtypes

    International Nuclear Information System (INIS)

    Kim, Ja Young; Chang, Sei Kyung; Lee, Bo Mi; Shin, Hyun Soo; Park, Heily

    2012-01-01

    To determine whether triple negative (TN) early stage breast cancers have poorer survival rates compared with other molecular types. Between August 2000 and July 2006, patients diagnosed with stage I, II early stage breast cancers, in whom all three markers (estrogen receptor, progesterone receptor, and human epidermal growth factor receptor [HER]-2) were available and treated with modified radical mastectomy or breast conserving surgery followed by radiotherapy, were retrospectively reviewed. Of 446 patients, 94 (21.1%) were classified as TN, 57 (12.8%) as HER-2 type, and 295 (66.1%) as luminal. TN was more frequently associated with young patients younger than 35 years old (p = 0.002), higher histologic grade (p 0.05). We found that patients with TN early stage breast cancers had no difference in survival rates compared with other molecular subtypes. Prospective study in homogeneous treatment group will need for a prognosis of TN early stage breast cancer.

  17. Hereditary breast cancer: from molecular pathology to tailored therapies.

    Science.gov (United States)

    Tan, D S P; Marchiò, C; Reis-Filho, J S

    2008-10-01

    Hereditary breast cancer accounts for up to 5-10% of all breast carcinomas. Recent studies have demonstrated that mutations in two high-penetrance genes, namely BRCA1 and BRCA2, are responsible for about 16% of the familial risk of breast cancer. Even though subsequent studies have failed to find another high-penetrance breast cancer susceptibility gene, several genes that confer a moderate to low risk of breast cancer development have been identified; moreover, hereditary breast cancer can be part of multiple cancer syndromes. In this review we will focus on the hereditary breast carcinomas caused by mutations in BRCA1, BRCA2, Fanconi anaemia (FANC) genes, CHK2 and ATM tumour suppressor genes. We describe the hallmark histological features of these carcinomas compared with non-hereditary breast cancers and show how an accurate histopathological diagnosis may help improve the identification of patients to be screened for mutations. Finally, novel therapeutic approaches to treat patients with BRCA1 and BRCA2 germ line mutations, including cross-linking agents and PARP inhibitors, are discussed.

  18. A Comprehensive Pan-Cancer Molecular Study of Gynecologic and Breast Cancers

    NARCIS (Netherlands)

    Berger, Ashton C.; Korkut, Anil; Kanchi, Rupa S.; Hegde, Apurva M.; Lenoir, Walter; Liu, Wenbin; Liu, Yuexin; Fan, Huihui; Shen, Hui; Ravikumar, Visweswaran; Rao, Arvind; Schultz, Andre; Li, Xubin; Sumazin, Pavel; Williams, Cecilia; Mestdagh, Pieter; Gunaratne, Preethi H.; Yau, Christina; Bowlby, Reanne; Robertson, A. Gordon; Tiezzi, Daniel G.; Wang, Chen; Cherniack, Andrew D.; Godwin, Andrew K.; Kuderer, Nicole M.; Rader, Janet S.; Zuna, Rosemary E.; Sood, Anil K.; Lazar, Alexander J.; Ojesina, Akinyemi I.; Adebamowo, Clement; Adebamowo, Sally N.; Baggerly, Keith A.; Chen, Ting Wen; Chiu, Hua Sheng; Lefever, Steve; Liu, Liang; MacKenzie, Karen; Orsulic, Sandra; Roszik, Jason; Shelley, Carl Simon; Song, Qianqian; Vellano, Christopher P.; Wentzensen, Nicolas; Caesar-Johnson, Samantha J.; Demchok, John A.; Felau, Ina; Kasapi, Melpomeni; Ferguson, Martin L.; Hutter, Carolyn M.; Sofia, Heidi J.; Tarnuzzer, Roy; Wang, Zhining; Yang, Liming; Zenklusen, Jean C.; Zhang, Jiashan (Julia); Chudamani, Sudha; Liu, Jia; Lolla, Laxmi; Naresh, Rashi; Pihl, Todd; Sun, Qiang; Wan, Yunhu; Wu, Ye; Cho, Juok; DeFreitas, Timothy; Frazer, Scott; Gehlenborg, Nils; Getz, Gad; Heiman, David I.; Kim, Jaegil; Lawrence, Michael S.; Lin, Pei; Meier, Sam; Noble, Michael S.; Saksena, Gordon; Voet, Doug; Zhang, Hailei; Bernard, Brady; Chambwe, Nyasha; Dhankani, Varsha; Knijnenburg, Theo; Kramer, Roger; Leinonen, Kalle; Liu, Yuexin; Miller, Michael; Reynolds, Sheila; Shmulevich, Ilya; Thorsson, Vesteinn; Zhang, Wei; Akbani, Rehan; Broom, Bradley M.; Hegde, Apurva M.; Ju, Zhenlin; Kanchi, Rupa S.; Korkut, Anil; Li, Jun; Liang, Han; Ling, Shiyun; Liu, Wenbin; Lu, Yiling; Mills, Gordon B.; Ng, Kwok Shing; Rao, Arvind; Ryan, Michael; Wang, Jing; Weinstein, John N.; Zhang, Jiexin; Abeshouse, Adam; Armenia, Joshua; Chakravarty, Debyani; Chatila, Walid K.; de Bruijn, Ino; Gao, Jianjiong; Gross, Benjamin E.; Heins, Zachary J.; Kundra, Ritika; La, Konnor; Ladanyi, Marc; Luna, Augustin; Nissan, Moriah G.; Ochoa, Angelica; Phillips, Sarah M.; Reznik, Ed; Sanchez-Vega, Francisco; Sander, Chris; Schultz, Nikolaus; Sheridan, Robert; Sumer, S. Onur; Sun, Yichao; Taylor, Barry S.; Wang, Jioajiao; Zhang, Hongxin; Anur, Pavana; Peto, Myron; Spellman, Paul; Benz, Christopher; Stuart, Joshua M.; Wong, Christopher K.; Yau, Christina; Hayes, D. Neil; Parker, Joel S.; Wilkerson, Matthew D.; Ally, Adrian; Balasundaram, Miruna; Bowlby, Reanne; Brooks, Denise; Carlsen, Rebecca; Chuah, Eric; Dhalla, Noreen; Holt, Robert; Jones, Steven J.M.; Kasaian, Katayoon; Lee, Darlene; Ma, Yussanne; Marra, Marco A.; Mayo, Michael; Moore, Richard A.; Mungall, Andrew J.; Mungall, Karen; Robertson, A. Gordon; Sadeghi, Sara; Schein, Jacqueline E.; Sipahimalani, Payal; Tam, Angela; Thiessen, Nina; Tse, Kane; Wong, Tina; Berger, Ashton C.; Beroukhim, Rameen; Cherniack, Andrew D.; Cibulskis, Carrie; Gabriel, Stacey B.; Gao, Galen F.; Ha, Gavin; Meyerson, Matthew; Schumacher, Steven E.; Shih, Juliann; Kucherlapati, Melanie H.; Kucherlapati, Raju S.; Baylin, Stephen; Cope, Leslie; Danilova, Ludmila; Bootwalla, Moiz S.; Lai, Phillip H.; Maglinte, Dennis T.; Van Den Berg, David J.; Weisenberger, Daniel J.; Auman, J. Todd; Balu, Saianand; Bodenheimer, Tom; Fan, Cheng; Hoadley, Katherine A.; Hoyle, Alan P.; Jefferys, Stuart R.; Jones, Corbin D.; Meng, Shaowu; Mieczkowski, Piotr A.; Mose, Lisle E.; Perou, Amy H.; Perou, Charles M.; Roach, Jeffrey; Shi, Yan; Simons, Janae V.; Skelly, Tara; Soloway, Matthew G.; Tan, Donghui; Veluvolu, Umadevi; Fan, Huihui; Hinoue, Toshinori; Laird, Peter W.; Shen, Hui; Zhou, Wanding; Bellair, Michelle; Chang, Kyle; Covington, Kyle; Creighton, Chad J.; Dinh, Huyen; Doddapaneni, Harsha Vardhan; Donehower, Lawrence A.; Drummond, Jennifer; Gibbs, Richard A.; Glenn, Robert; Hale, Walker; Han, Yi; Hu, Jianhong; Korchina, Viktoriya; Lee, Sandra; Lewis, Lora; Li, Wei; Liu, Xiuping; Morgan, Margaret; Morton, Donna; Muzny, Donna; Santibanez, Jireh; Sheth, Margi; Shinbrot, Eve; Wang, Linghua; Wang, Min; Wheeler, David A.; Xi, Liu; Zhao, Fengmei; Hess, Julian; Appelbaum, Elizabeth L.; Bailey, Matthew; Cordes, Matthew G.; Ding, Li; Fronick, Catrina C.; Fulton, Lucinda A.; Fulton, Robert S.; Kandoth, Cyriac; Mardis, Elaine R.; McLellan, Michael D.; Miller, Christopher A.; Schmidt, Heather K.; Wilson, Richard K.; Crain, Daniel; Curley, Erin; Gardner, Johanna; Lau, Kevin; Mallery, David; Morris, Scott; Paulauskis, Joseph; Penny, Robert; Shelton, Candace; Shelton, Troy; Sherman, Mark; Thompson, Eric; Yena, Peggy; Bowen, Jay; Gastier-Foster, Julie M.; Gerken, Mark; Leraas, Kristen M.; Lichtenberg, Tara M.; Ramirez, Nilsa C.; Wise, Lisa; Zmuda, Erik; Corcoran, Niall; Costello, Tony; Hovens, Christopher; Carvalho, Andre L.; de Carvalho, Ana C.; Fregnani, José H.; Longatto-Filho, Adhemar; Reis, Rui M.; Scapulatempo-Neto, Cristovam; Silveira, Henrique C.S.; Vidal, Daniel O.; Burnette, Andrew; Eschbacher, Jennifer; Hermes, Beth; Noss, Ardene; Singh, Rosy; Anderson, Matthew L.; Castro, Patricia D.; Ittmann, Michael; Huntsman, David; Kohl, Bernard; Le, Xuan; Thorp, Richard; Andry, Chris; Duffy, Elizabeth R.; Lyadov, Vladimir; Paklina, Oxana; Setdikova, Galiya; Shabunin, Alexey; Tavobilov, Mikhail; McPherson, Christopher; Warnick, Ronald; Berkowitz, Ross; Cramer, Daniel; Feltmate, Colleen; Horowitz, Neil; Kibel, Adam; Muto, Michael; Raut, Chandrajit P.; Malykh, Andrei; Barnholtz-Sloan, Jill S.; Barrett, Wendi; Devine, Karen; Fulop, Jordonna; Ostrom, Quinn T.; Shimmel, Kristen; Wolinsky, Yingli; Sloan, Andrew E.; De Rose, Agostino; Giuliante, Felice; Goodman, Marc; Karlan, Beth Y.; Hagedorn, Curt H.; Eckman, John; Harr, Jodi; Myers, Jerome; Tucker, Kelinda; Zach, Leigh Anne; Deyarmin, Brenda; Hu, Hai; Kvecher, Leonid; Larson, Caroline; Mural, Richard J.; Somiari, Stella; Vicha, Ales; Zelinka, Tomas; Bennett, Joseph; Iacocca, Mary; Rabeno, Brenda; Swanson, Patricia; Latour, Mathieu; Lacombe, Louis; Têtu, Bernard; Bergeron, Alain; McGraw, Mary; Staugaitis, Susan M.; Chabot, John; Hibshoosh, Hanina; Sepulveda, Antonia; Su, Tao; Wang, Timothy; Potapova, Olga; Voronina, Olga; Desjardins, Laurence; Mariani, Odette; Roman-Roman, Sergio; Sastre, Xavier; Stern, Marc Henri; Cheng, Feixiong; Signoretti, Sabina; Berchuck, Andrew; Bigner, Darell; Lipp, Eric; Marks, Jeffrey; McCall, Shannon; McLendon, Roger; Secord, Angeles; Sharp, Alexis; Behera, Madhusmita; Brat, Daniel J.; Chen, Amy; Delman, Keith; Force, Seth; Khuri, Fadlo; Magliocca, Kelly; Maithel, Shishir; Olson, Jeffrey J.; Owonikoko, Taofeek; Pickens, Alan; Ramalingam, Suresh; Shin, Dong M.; Sica, Gabriel; Van Meir, Erwin G.; Zhang, Hongzheng; Eijckenboom, Wil; Gillis, Ad; Korpershoek, Esther; Looijenga, Leendert; Oosterhuis, Wolter; Stoop, Hans; van Kessel, Kim E.; Zwarthoff, Ellen C.; Calatozzolo, Chiara; Cuppini, Lucia; Cuzzubbo, Stefania; DiMeco, Francesco; Finocchiaro, Gaetano; Mattei, Luca; Perin, Alessandro; Pollo, Bianca; Chen, Chu; Houck, John; Lohavanichbutr, Pawadee; Hartmann, Arndt; Stoehr, Christine; Stoehr, Robert; Taubert, Helge; Wach, Sven; Wullich, Bernd; Kycler, Witold; Murawa, Dawid; Wiznerowicz, Maciej; Chung, Ki; Edenfield, W. Jeffrey; Martin, Julie; Baudin, Eric; Bubley, Glenn; Bueno, Raphael; De Rienzo, Assunta; Richards, William G.; Kalkanis, Steven; Mikkelsen, Tom; Noushmehr, Houtan; Scarpace, Lisa; Girard, Nicolas; Aymerich, Marta; Campo, Elias; Giné, Eva; Guillermo, Armando López; Van Bang, Nguyen; Hanh, Phan Thi; Phu, Bui Duc; Tang, Yufang; Colman, Howard; Evason, Kimberley; Dottino, Peter R.; Martignetti, John A.; Gabra, Hani; Juhl, Hartmut; Akeredolu, Teniola; Stepa, Serghei; Hoon, Dave; Ahn, Keunsoo; Kang, Koo Jeong; Beuschlein, Felix; Breggia, Anne; Birrer, Michael; Bell, Debra; Borad, Mitesh; Bryce, Alan H.; Castle, Erik; Chandan, Vishal; Cheville, John; Copland, John A.; Farnell, Michael; Flotte, Thomas; Giama, Nasra; Ho, Thai; Kendrick, Michael; Kocher, Jean Pierre; Kopp, Karla; Moser, Catherine; Nagorney, David; O'Brien, Daniel; O'Neill, Brian Patrick; Patel, Tushar; Petersen, Gloria; Que, Florencia; Rivera, Michael; Roberts, Lewis; Smallridge, Robert; Smyrk, Thomas; Stanton, Melissa; Thompson, R. Houston; Torbenson, Michael; Yang, Ju Dong; Zhang, Lizhi; Brimo, Fadi; Ajani, Jaffer A.; Angulo Gonzalez, Ana Maria; Behrens, Carmen; Bondaruk, Jolanta; Broaddus, Russell; Czerniak, Bogdan; Esmaeli, Bita; Fujimoto, Junya; Gershenwald, Jeffrey; Guo, Charles; Lazar, Alexander J.; Logothetis, Christopher; Meric-Bernstam, Funda; Moran, Cesar; Ramondetta, Lois; Rice, David; Sood, Anil; Tamboli, Pheroze; Thompson, Timothy; Troncoso, Patricia; Tsao, Anne; Wistuba, Ignacio; Carter, Candace; Haydu, Lauren; Hersey, Peter; Jakrot, Valerie; Kakavand, Hojabr; Kefford, Richard; Lee, Kenneth; Long, Georgina; Mann, Graham; Quinn, Michael; Saw, Robyn; Scolyer, Richard; Shannon, Kerwin; Spillane, Andrew; Stretch, Jonathan; Synott, Maria; Thompson, John; Wilmott, James; Al-Ahmadie, Hikmat; Chan, Timothy A.; Ghossein, Ronald; Gopalan, Anuradha; Levine, Douglas A.; Reuter, Victor; Singer, Samuel; Singh, Bhuvanesh; Tien, Nguyen Viet; Broudy, Thomas; Mirsaidi, Cyrus; Nair, Praveen; Drwiega, Paul; Miller, Judy; Smith, Jennifer; Zaren, Howard; Park, Joong Won; Hung, Nguyen Phi; Kebebew, Electron; Linehan, W. Marston; Metwalli, Adam R.; Pacak, Karel; Pinto, Peter A.; Schiffman, Mark; Schmidt, Laura S.; Vocke, Cathy D.; Wentzensen, Nicolas; Worrell, Robert; Yang, Hannah; Moncrieff, Marc; Goparaju, Chandra; Melamed, Jonathan; Pass, Harvey; Botnariuc, Natalia; Caraman, Irina; Cernat, Mircea; Chemencedji, Inga; Clipca, Adrian; Doruc, Serghei; Gorincioi, Ghenadie; Mura, Sergiu; Pirtac, Maria; Stancul, Irina; Tcaciuc, Diana; Albert, Monique; Alexopoulou, Iakovina; Arnaout, Angel; Bartlett, John; Engel, Jay; Gilbert, Sebastien; Parfitt, Jeremy; Sekhon, Harman; Thomas, George; Rassl, Doris M.; Rintoul, Robert C.; Bifulco, Carlo; Tamakawa, Raina; Urba, Walter; Hayward, Nicholas; Timmers, Henri; Antenucci, Anna; Facciolo, Francesco; Grazi, Gianluca; Marino, Mirella; Merola, Roberta; de Krijger, Ronald; Gimenez-Roqueplo, Anne Paule; Piché, Alain; Chevalier, Simone; McKercher, Ginette; Birsoy, Kivanc; Barnett, Gene; Brewer, Cathy; Farver, Carol; Naska, Theresa; Pennell, Nathan A.; Raymond, Daniel; Schilero, Cathy; Smolenski, Kathy; Williams, Felicia; Morrison, Carl; Borgia, Jeffrey A.; Liptay, Michael J.; Pool, Mark; Seder, Christopher W.; Junker, Kerstin; Omberg, Larsson; Dinkin, Mikhail; Manikhas, George; Alvaro, Domenico; Bragazzi, Maria Consiglia; Cardinale, Vincenzo; Carpino, Guido; Gaudio, Eugenio; Chesla, David; Cottingham, Sandra; Dubina, Michael; Moiseenko, Fedor; Dhanasekaran, Renumathy; Becker, Karl Friedrich; Janssen, Klaus Peter; Slotta-Huspenina, Julia; Abdel-Rahman, Mohamed H.; Aziz, Dina; Bell, Sue; Cebulla, Colleen M.; Davis, Amy; Duell, Rebecca; Elder, J. Bradley; Hilty, Joe; Kumar, Bahavna; Lang, James; Lehman, Norman L.; Mandt, Randy; Nguyen, Phuong; Pilarski, Robert; Rai, Karan; Schoenfield, Lynn; Senecal, Kelly; Wakely, Paul; Hansen, Paul; Lechan, Ronald; Powers, James; Tischler, Arthur; Grizzle, William E.; Sexton, Katherine C.; Kastl, Alison; Henderson, Joel; Porten, Sima; Waldmann, Jens; Fassnacht, Martin; Asa, Sylvia L.; Schadendorf, Dirk; Couce, Marta; Graefen, Markus; Huland, Hartwig; Sauter, Guido; Schlomm, Thorsten; Simon, Ronald; Tennstedt, Pierre; Olabode, Oluwole; Nelson, Mark; Bathe, Oliver; Carroll, Peter R.; Chan, June M.; Disaia, Philip; Glenn, Pat; Kelley, Robin K.; Landen, Charles N.; Phillips, Joanna; Prados, Michael; Simko, Jeffry; Smith-McCune, Karen; VandenBerg, Scott; Roggin, Kevin; Fehrenbach, Ashley; Kendler, Ady; Sifri, Suzanne; Steele, Ruth; Jimeno, Antonio; Carey, Francis; Forgie, Ian; Mannelli, Massimo; Carney, Michael; Hernandez, Brenda; Campos, Benito; Herold-Mende, Christel; Jungk, Christin; Unterberg, Andreas; von Deimling, Andreas; Bossler, Aaron; Galbraith, Joseph; Jacobus, Laura; Knudson, Michael; Knutson, Tina; Ma, Deqin; Milhem, Mohammed; Sigmund, Rita; Godwin, Andrew K.; Madan, Rashna; Rosenthal, Howard G.; Adebamowo, Clement; Adebamowo, Sally N.; Boussioutas, Alex; Beer, David; Giordano, Thomas; Mes-Masson, Anne Marie; Saad, Fred; Bocklage, Therese; Landrum, Lisa; Mannel, Robert; Moore, Kathleen; Moxley, Katherine; Postier, Russel; Walker, Joan; Zuna, Rosemary; Feldman, Michael; Valdivieso, Federico; Dhir, Rajiv; Luketich, James; Mora Pinero, Edna M.; Quintero-Aguilo, Mario; Carlotti, Carlos Gilberto; Dos Santos, Jose Sebastião; Kemp, Rafael; Sankarankuty, Ajith; Tirapelli, Daniela; Catto, James; Agnew, Kathy; Swisher, Elizabeth; Creaney, Jenette; Robinson, Bruce; Shelley, Carl Simon; Godwin, Eryn M.; Kendall, Sara; Shipman, Cassaundra; Bradford, Carol; Carey, Thomas; Haddad, Andrea; Moyer, Jeffey; Peterson, Lisa; Prince, Mark; Rozek, Laura; Wolf, Gregory; Bowman, Rayleen; Fong, Kwun M.; Yang, Ian; Korst, Robert; Rathmell, W. Kimryn; Fantacone-Campbell, J. Leigh; Hooke, Jeffrey A.; Kovatich, Albert J.; Shriver, Craig D.; DiPersio, John; Drake, Bettina; Govindan, Ramaswamy; Heath, Sharon; Ley, Timothy; Van Tine, Brian; Westervelt, Peter; Rubin, Mark A.; Lee, Jung Il; Aredes, Natália D.; Mariamidze, Armaz; Weinstein, John N.; Mills, Gordon B.; Levine, Douglas A.; Akbani, Rehan

    2018-01-01

    We analyzed molecular data on 2,579 tumors from The Cancer Genome Atlas (TCGA) of four gynecological types plus breast. Our aims were to identify shared and unique molecular features, clinically significant subtypes, and potential therapeutic targets. We found 61 somatic copy-number alterations

  19. Molecular epidemiology, and possible real-world applications in breast cancer.

    Science.gov (United States)

    Ito, Hidemi; Matsuo, Keitaro

    2016-01-01

    Gene-environment interaction, a key idea in molecular epidemiology, has enabled the development of personalized medicine. This concept includes personalized prevention. While genome-wide association studies have identified a number of genetic susceptibility loci in breast cancer risk, however, the application of this knowledge to practical prevention is still underway. Here, we briefly review the history of molecular epidemiology and its progress in breast cancer epidemiology. We then introduce our experience with the trial combination of GWAS-identified loci and well-established lifestyle and reproductive risk factors in the risk prediction of breast cancer. Finally, we report our exploration of the cumulative risk of breast cancer based on this risk prediction model as a potential tool for individual risk communication, including genetic risk factors and gene-environment interaction with obesity.

  20. Breast-specific gamma-imaging: molecular imaging of the breast using 99mTc-sestamibi and a small-field-of-view gamma-camera.

    Science.gov (United States)

    Jones, Elizabeth A; Phan, Trinh D; Blanchard, Deborah A; Miley, Abbe

    2009-12-01

    Breast-specific gamma-imaging (BSGI), also known as molecular breast imaging, is breast scintigraphy using a small-field-of-view gamma-camera and (99m)Tc-sestamibi. There are many different types of breast cancer, and many have characteristics making them challenging to detect by mammography and ultrasound. BSGI is a cost-effective, highly sensitive and specific technique that complements other imaging modalities currently being used to identify malignant lesions in the breast. Using the current Society of Nuclear Medicine guidelines for breast scintigraphy, Legacy Good Samaritan Hospital began conducting BSGI, breast scintigraphy with a breast-optimized gamma-camera. In our experience, optimal imaging has been conducted in the Breast Center by a nuclear medicine technologist. In addition, the breast radiologists read the BSGI images in correlation with the mammograms, ultrasounds, and other imaging studies performed. By modifying the current Society of Nuclear Medicine protocol to adapt it to the practice of breast scintigraphy with these new systems and by providing image interpretation in conjunction with the other breast imaging studies, our center has found BSGI to be a valuable adjunctive procedure in the diagnosis of breast cancer. The development of a small-field-of-view gamma-camera, designed to optimize breast imaging, has resulted in improved detection capabilities, particularly for lesions less than 1 cm. Our experience with this procedure has proven to aid in the clinical work-up of many of our breast patients. After reading this article, the reader should understand the history of breast scintigraphy, the pharmaceutical used, patient preparation and positioning, imaging protocol guidelines, clinical indications, and the role of breast scintigraphy in breast cancer diagnosis.

  1. Molecular Epidemiology of Breast Cancer in Korean Women

    National Research Council Canada - National Science Library

    Gabrielson, Edward

    2002-01-01

    ... profiles as objective measures of breast cancer phenotypes. The study is being conducted using samples from Korean women because this likely represents a relatively homogeneous population from genetic and cultural perspectives...

  2. Breast cancer in Ethiopia: evidence for geographic difference in the distribution of molecular subtypes in Africa.

    Science.gov (United States)

    Hadgu, Endale; Seifu, Daniel; Tigneh, Wondemagegnhu; Bokretsion, Yonas; Bekele, Abebe; Abebe, Markos; Sollie, Thomas; Merajver, Sofia D; Karlsson, Christina; Karlsson, Mats G

    2018-02-14

    Breast cancer is a heterogeneous disease with several morphological and molecular subtypes. Widely accepted molecular classification system uses assessment of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and proliferation marker Ki67. Few studies have been conducted on the incidence and molecular types of breast cancer in Sub-Saharan Africa. Previous studies mainly from Western and Central Africa, showed breast cancer to occur at younger ages and to present with aggressive features, such as high-grade, advanced stage and triple-negative phenotype (negative for ER, PR and HER2). Limited data from East Africa including Ethiopia however shows hormone receptor negative tumors to account for a lower proportion of all breast cancers than has been reported from elsewhere in Africa. In this study from Tikur Anbessa Specialized Hospital, 114 breast cancer patients diagnosed between 2012 and 2015 were enrolled. ER, PR, Ki67 and HER2 receptor status were assessed using immunohistochemistry from tissue microarrays. FISH was used for assessment of gene amplification in all equivocal tumor samples and for confirmation in HER2-enriched cases. The distribution of molecular subtypes was: Luminal A: 40%; Luminal B: 26%; HER2-enriched: 10%; TNBC: 23%. ER were positive in 65% of all tumors and 43% the cases were positive for PR. There was statistically significant difference in median age at diagnosis between the molecular subtypes (P molecular subtypes in different age ranges with Luminal B subtype being more common at younger ages (median = 36) and Luminal A subtype more prevalent at older ages (median = 42). There were no statistically significant differences in tumor grade, histology, and stage between the molecular subtypes of breast cancer. The present study detected Luminal A breast cancer to be the most common subtype and reveals a relatively low rate of hormone receptor negative and TNBC. Our findings and

  3. Intra-tumor heterogeneity in breast cancer has limited impact on transcriptomic-based molecular profiling.

    Science.gov (United States)

    Karthik, Govindasamy-Muralidharan; Rantalainen, Mattias; Stålhammar, Gustav; Lövrot, John; Ullah, Ikram; Alkodsi, Amjad; Ma, Ran; Wedlund, Lena; Lindberg, Johan; Frisell, Jan; Bergh, Jonas; Hartman, Johan

    2017-11-29

    Transcriptomic profiling of breast tumors provides opportunity for subtyping and molecular-based patient stratification. In diagnostic applications the specimen profiled should be representative of the expression profile of the whole tumor and ideally capture properties of the most aggressive part of the tumor. However, breast cancers commonly exhibit intra-tumor heterogeneity at molecular, genomic and in phenotypic level, which can arise during tumor evolution. Currently it is not established to what extent a random sampling approach may influence molecular breast cancer diagnostics. In this study we applied RNA-sequencing to quantify gene expression in 43 pieces (2-5 pieces per tumor) from 12 breast tumors (Cohort 1). We determined molecular subtype and transcriptomic grade for all tumor pieces and analysed to what extent pieces originating from the same tumors are concordant or discordant with each other. Additionally, we validated our finding in an independent cohort consisting of 19 pieces (2-6 pieces per tumor) from 6 breast tumors (Cohort 2) profiled using microarray technique. Exome sequencing was also performed on this cohort, to investigate the extent of intra-tumor genomic heterogeneity versus the intra-tumor molecular subtype classifications. Molecular subtyping was consistent in 11 out of 12 tumors and transcriptomic grade assignments were consistent in 11 out of 12 tumors as well. Molecular subtype predictions revealed consistent subtypes in four out of six patients in this cohort 2. Interestingly, we observed extensive intra-tumor genomic heterogeneity in these tumor pieces but not in their molecular subtype classifications. Our results suggest that macroscopic intra-tumoral transcriptomic heterogeneity is limited and unlikely to have an impact on molecular diagnostics for most patients.

  4. Background parenchymal uptake on molecular breast imaging as a breast cancer risk factor: a case-control study.

    Science.gov (United States)

    Hruska, Carrie B; Scott, Christopher G; Conners, Amy Lynn; Whaley, Dana H; Rhodes, Deborah J; Carter, Rickey E; O'Connor, Michael K; Hunt, Katie N; Brandt, Kathleen R; Vachon, Celine M

    2016-04-26

    Molecular breast imaging (MBI) is a functional test used for supplemental screening of women with mammographically dense breasts. Additionally, MBI depicts variable levels of background parenchymal uptake (BPU) within nonmalignant, dense fibroglandular tissue. We investigated whether BPU is a risk factor for breast cancer. We conducted a retrospective case-control study of 3027 eligible women who had undergone MBI between February 2004 and February 2014. Sixty-two incident breast cancer cases were identified. A total of 179 controls were matched on age, menopausal status, and MBI year. Two radiologists blinded to case status independently assessed BPU as one of four categories: photopenic, minimal to mild, moderate, or marked. Conditional logistic regression analysis was performed to estimate the associations (OR) of BPU categories (moderate or marked vs. minimal to mild or photopenic) and breast cancer risk, adjusted for other risk factors. The median age was 60.2 years (range 38-86 years) for cases vs. 60.2 years (range 38-88 years) for controls (p = 0.88). Women with moderate or marked BPU had a 3.4-fold (95 % CI 1.6-7.3) and 4.8-fold (95 % CI 2.1-10.8) increased risk of breast cancer, respectively, compared with women with photopenic or minimal to mild BPU, for two radiologists. The results were similar after adjustment for BI-RADS density (OR 3.3 [95 % CI 1.6-7.2] and OR 4.6 [95 % CI 2.1-10.5]) or postmenopausal hormone use (OR 3.6 [95 % CI 1.7-7.7] and OR 5.0 [95 % CI 2.2-11.4]). The association of BPU with breast cancer remained in analyses limited to postmenopausal women only (OR 3.8 [95 % CI 1.5-9.3] and OR 4.1 [95 % CI 1.6-10.2]) and invasive breast cancer cases only (OR 3.6 [95 % CI 1.5-8.8] and OR 4.4 [95 % CI 1.7-11.1]). Variable BPU was observed among women with similar mammographic density; the distribution of BPU categories differed across density categories (p factor for breast cancer. Among women with dense breasts, who comprise

  5. Correlation of microarray-based breast cancer molecular subtypes and clinical outcomes: implications for treatment optimization

    Directory of Open Access Journals (Sweden)

    Hsu Hui-Chi

    2011-04-01

    Full Text Available Abstract Background Optimizing treatment through microarray-based molecular subtyping is a promising method to address the problem of heterogeneity in breast cancer; however, current application is restricted to prediction of distant recurrence risk. This study investigated whether breast cancer molecular subtyping according to its global intrinsic biology could be used for treatment customization. Methods Gene expression profiling was conducted on fresh frozen breast cancer tissue collected from 327 patients in conjunction with thoroughly documented clinical data. A method of molecular subtyping based on 783 probe-sets was established and validated. Statistical analysis was performed to correlate molecular subtypes with survival outcome and adjuvant chemotherapy regimens. Heterogeneity of molecular subtypes within groups sharing the same distant recurrence risk predicted by genes of the Oncotype and MammaPrint predictors was studied. Results We identified six molecular subtypes of breast cancer demonstrating distinctive molecular and clinical characteristics. These six subtypes showed similarities and significant differences from the Perou-Sørlie intrinsic types. Subtype I breast cancer was in concordance with chemosensitive basal-like intrinsic type. Adjuvant chemotherapy of lower intensity with CMF yielded survival outcome similar to those of CAF in this subtype. Subtype IV breast cancer was positive for ER with a full-range expression of HER2, responding poorly to CMF; however, this subtype showed excellent survival when treated with CAF. Reduced expression of a gene associated with methotrexate sensitivity in subtype IV was the likely reason for poor response to methotrexate. All subtype V breast cancer was positive for ER and had excellent long-term survival with hormonal therapy alone following surgery and/or radiation therapy. Adjuvant chemotherapy did not provide any survival benefit in early stages of subtype V patients. Subtype V was

  6. Correlation of microarray-based breast cancer molecular subtypes and clinical outcomes: implications for treatment optimization

    International Nuclear Information System (INIS)

    Kao, Kuo-Jang; Chang, Kai-Ming; Hsu, Hui-Chi; Huang, Andrew T

    2011-01-01

    Optimizing treatment through microarray-based molecular subtyping is a promising method to address the problem of heterogeneity in breast cancer; however, current application is restricted to prediction of distant recurrence risk. This study investigated whether breast cancer molecular subtyping according to its global intrinsic biology could be used for treatment customization. Gene expression profiling was conducted on fresh frozen breast cancer tissue collected from 327 patients in conjunction with thoroughly documented clinical data. A method of molecular subtyping based on 783 probe-sets was established and validated. Statistical analysis was performed to correlate molecular subtypes with survival outcome and adjuvant chemotherapy regimens. Heterogeneity of molecular subtypes within groups sharing the same distant recurrence risk predicted by genes of the Oncotype and MammaPrint predictors was studied. We identified six molecular subtypes of breast cancer demonstrating distinctive molecular and clinical characteristics. These six subtypes showed similarities and significant differences from the Perou-Sørlie intrinsic types. Subtype I breast cancer was in concordance with chemosensitive basal-like intrinsic type. Adjuvant chemotherapy of lower intensity with CMF yielded survival outcome similar to those of CAF in this subtype. Subtype IV breast cancer was positive for ER with a full-range expression of HER2, responding poorly to CMF; however, this subtype showed excellent survival when treated with CAF. Reduced expression of a gene associated with methotrexate sensitivity in subtype IV was the likely reason for poor response to methotrexate. All subtype V breast cancer was positive for ER and had excellent long-term survival with hormonal therapy alone following surgery and/or radiation therapy. Adjuvant chemotherapy did not provide any survival benefit in early stages of subtype V patients. Subtype V was consistent with a unique subset of luminal A intrinsic

  7. Next Generation Molecular Histology Using Highly Multiplexed Ion Beam Imaging (MIBI) of Breast Cancer Tissue Specimens for Enhanced Clinical Guidance

    Science.gov (United States)

    2016-07-01

    AWARD NUMBER: W81XWH- 14-1-0192 TITLE: Next-Generation Molecular Histology Using Highly Multiplexed Ion Beam Imaging (MIBI) of Breast Cancer...DATES COVERED 4. TITLE AND SUBTITLE Next-Generation Molecular Histology Using Highly Multiplexed Ion Beam Imaging (MIBI) of Breast Cancer Tissue

  8. Investigation of the molecular relationship between breast cancer and obesity by candidate gene prioritization methods

    Directory of Open Access Journals (Sweden)

    Saba Garshasbi

    2015-10-01

    Full Text Available Background: Cancer and obesity are two major public health concerns. More than 12 million cases of cancer are reported annually. Many reports confirmed obesity as a risk factor for cancer. The molecular relationship between obesity and breast cancer has not been clear yet. The purpose of this study was to investigate priorities of effective genes in the molecular relationship between obesity and breast cancer. Methods: In this study, computer simulation method was used for prioritizing the genes that involved in the molecular links between obesity and breast cancer in laboratory of systems biology and bioinformatics (LBB, Tehran University, Tehran, Iran, from March to July 2014. In this study, ENDEAVOUR software was used for prioritizing the genes and integrating multiple data sources was used for data analysis. Training genes were selected from effective genes in obesity and/or breast cancer. Two groups of candidate genes were selected. The first group was included the existential genes in 5 common region chromosomes (between obesity and breast cancer and the second group was included the results of genes microarray data analysis of research Creighton, et al (In 2012 on patients with breast cancer. The microarray data were analyzed with GER2 software (R online software on GEO website. Finally, both training and candidate genes were entered in ENDEAVOUR software package. Results: The candidate genes were prioritized to four style and five genes in ten of the first priorities were repeated twice. In other word, the outcome of prioritizing of 72 genes (Product of microarray data analysis and genes of 5 common chromosome regions (Between obesity and breast cancer showed, 5 genes (TNFRSF10B, F2, IGFALS, NTRK3 and HSP90B1 were the priorities in the molecular connection between obesity and breast cancer. Conclusion: There are some common genes between breast cancer and obesity. So, molecular relationship is confirmed. In this study the possible effect

  9. System geometry optimization for molecular breast tomosynthesis with focusing multi-pinhole collimators

    Science.gov (United States)

    van Roosmalen, Jarno; Beekman, Freek J.; Goorden, Marlies C.

    2018-01-01

    Imaging of 99mTc-labelled tracers is gaining popularity for detecting breast tumours. Recently, we proposed a novel design for molecular breast tomosynthesis (MBT) based on two sliding focusing multi-pinhole collimators that scan a modestly compressed breast. Simulation studies indicate that MBT has the potential to improve the tumour-to-background contrast-to-noise ratio significantly over state-of-the-art planar molecular breast imaging. The aim of the present paper is to optimize the collimator-detector geometry of MBT. Using analytical models, we first optimized sensitivity at different fixed system resolutions (ranging from 5 to 12 mm) by tuning the pinhole diameters and the distance between breast and detector for a whole series of automatically generated multi-pinhole designs. We evaluated both MBT with a conventional continuous crystal detector with 3.2 mm intrinsic resolution and with a pixelated detector with 1.6 mm pixels. Subsequently, full system simulations of a breast phantom containing several lesions were performed for the optimized geometry at each system resolution for both types of detector. From these simulations, we found that tumour-to-background contrast-to-noise ratio was highest for systems in the 7 mm-10 mm system resolution range over which it hardly varied. No significant differences between the two detector types were found.

  10. Evaluation of the pathological response and prognosis following neoadjuvant chemotherapy in molecular subtypes of breast cancer

    Directory of Open Access Journals (Sweden)

    Zhao Y

    2015-06-01

    Full Text Available Yue Zhao,1 Xiaoqiu Dong,2 Rongguo Li,1 Xiao Ma,1 Jian Song,1 Yingjie Li,3 Dongwei Zhang1 1Department of General Surgery, Second Affiliated Hospital of Harbin Medical University, 2Department of Ultrasonography, Fourth Affiliated Hospital of Harbin Medical University, 3Department of Pathology, Second Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China Background: The pathological complete response of neoadjuvant chemotherapy for breast cancer correlates with the prognosis for survival. Tumors may have different prognoses according to their molecular subtypes. This study was performed to evaluate the relevance of the pathological response and prognosis following neoadjuvant chemotherapy in the molecular subtypes of breast cancer.Methods: A consecutive series of 88 patients with operable breast cancer treated with neoadjuvant chemotherapy was analyzed. Patients were classified into four molecular subtypes based on the immunohistochemistry profile of the estrogen receptor, progesterone receptor, HER2, and Ki-67. The histological response was assessed according to Miller-Payne grading (MPG and Residual Disease in Breast and Nodes (RDBN.Results: Ten patients (11.4% achieved a pathological complete response, assessed according to RDBN. The pathological complete response rate was 13.6% according to MPG. Patients with the triple-negative subtype were more likely to achieve a pathological complete response than those with luminal A breast cancer (P=0.03. MPG and RDBN are independent predictors of distant disease-free survival and local recurrence-free survival, but do not predict overall survival. Ki-67, size of invasive carcinoma, lymph nodes, molecular subtypes, MPG, and RDBN are important predictors of distant disease-free survival, local recurrence-free survival, and overall survival.Conclusion: MPG and RDBN were similarly related to the patient’s prognosis. MPG was more suitable for evaluation of distant disease

  11. Pattern of distant recurrence according to the molecular subtypes in Korean women with breast cancer

    Directory of Open Access Journals (Sweden)

    Park Hyung Seok

    2012-01-01

    Full Text Available Abstract Background Distant recurrence is one of the most important risk factors in overall survival, and distant recurrence is related to a complex biologic interaction of seed and soil factors. The aim of the study was to investigate the association between the molecular subtypes and patterns of distant recurrence in patients with breast cancer. Methods In an investigation of 313 women with breast cancer who underwent surgery from 1994 and 2000, the expressions of estrogen and progestrone receptor (ER/PR, and human epithelial receptor-2 (HER2 were evaluated. The subtypes were defined as luminal-A, luminal-HER2, HER2-enriched, and triple negative breast cancer (TNBC according to ER, PR, and HER2 status. Results Bone was the most common site of distant recurrence. The incidence of first distant recurrence site was significantly different among the subtypes. Brain metastasis was more frequent in the luminal-HER2 and TNBC subtypes. In subgroup analysis, overall survival in patients with distant recurrence after 24 months after surgery was significantly different among the subtypes. Conclusions Organ-specific metastasis may depend on the molecular subtype of breast cancer. Tailored strategies against distant metastasis concerning the molecular subtypes in breast cancer may be considered.

  12. Metastatic Organotropism: An Intrinsic Property of Breast Cancer Molecular Subtypes.

    Science.gov (United States)

    Wei, Shi; Siegal, Gene P

    2017-03-01

    It has long been known that some cancers have the propensity to metastasize to certain organs thus creating a nonrandom distribution of sites for distant relapse, a phenomenon known as "metastatic organotropism." Some of these examples include ovary primary to abdominal cavity, prostate primary to bone, and pancreas primary to liver. In contrast, other tumor types, such as mammary and renal cell carcinoma, can relapse in multiple organs although approximately half of advanced breast cancers metastasize to bone. On the other hand gene expression profiling studies have identified various breast cancer classes with prognostic significance. Recent studies have revealed that breast cancer subtypes differ not only in primary tumor characteristics but also in their metastatic behavior. In particular, the luminal tumors are remarkable for their significant bone-seeking phenotype; the HER2 subtype demonstrates a significant liver-homing characteristic; whereas so-called triple-negative breast cancers predispose to lung metastases. These findings suggest that this knowledge could potentially be utilized in the development of effective disease surveillance strategies in the pursuit of precision medicine, thus necessitating further investigation.

  13. Molecular profiles of progesterone receptor loss in human breast tumors

    NARCIS (Netherlands)

    Creighton, Chad J.; Kent Osborne, C.; van de Vijver, Marc J.; Foekens, John A.; Klijn, Jan G.; Horlings, Hugo M.; Nuyten, Dimitry; Wang, Yixin; Zhang, Yi; Chamness, Gary C.; Hilsenbeck, Susan G.; Lee, Adrian V.; Schiff, Rachel

    2009-01-01

    Background Patient prognosis and response to endocrine therapy in breast cancer correlate with protein expression of both estrogen receptor (ER) and progesterone receptor (PR), with poorer outcome in patients with ER+/PR- compared to ER+/PR+ tumors. Methods To better understand the underlying

  14. Review Article: Molecular Epidemiology of Breast Cancer: A Review ...

    African Journals Online (AJOL)

    The standard paradigm providing a general mechanistic explanation for the association of cumulative, excessive oestrogen exposure and breast cancer risk is that the proliferative stimulus provided by 17β-estradiol (E2) leads to the appearance of spontaneous mutations. Thus, the key contribution of E2) is the stimulation of ...

  15. Molecular Subtypes and Clinical Outcomes of Breast Cancer

    African Journals Online (AJOL)

    2010-01-04

    Jan 4, 2010 ... Some early work has started in earnest at both the. AKUH(N) and Kijabe Hospitals to try and stratify our breast cancer patients to those mentioned subtypes to help in both diagnosis and treatment. The limiting fac- tors are small numbers of patients expense to undertake the tests and lack of both internal ...

  16. Molecular Biology In Young Women With Breast Cancer: From Tumor Gene Expression To DNA Mutations.

    Science.gov (United States)

    Gómez-Flores-Ramos, Liliana; Castro-Sánchez, Andrea; Peña-Curiel, Omar; Mohar-Betancourt, Alejandro

    2017-01-01

    Young women with breast cancer (YWBC) represent roughly 15% of breast cancer (BC) cases in Latin America and other developing regions. Breast tumors occurring at an early age are more aggressive and have an overall worse prognosis compared to breast tumors in postmenopausal women. The expression of relevant proliferation biomarkers such as endocrine receptors and human epidermal growth factor receptor 2 appears to be unique in YWBC. Moreover, histopathological, molecular, genetic, and genomic studies have shown that YWBC exhibit a higher frequency of aggressive subtypes, differential tumor gene expression, increased genetic susceptibility, and specific genomic signatures, compared to older women with BC. This article reviews the current knowledge on tumor biology and genomic signatures in YWBC.

  17. Prediction consistency and clinical presentations of breast cancer molecular subtypes for Han Chinese population

    Directory of Open Access Journals (Sweden)

    Huang Chi-Cheng

    2012-09-01

    Full Text Available Abstract Background Breast cancer is a heterogeneous disease in terms of transcriptional aberrations; moreover, microarray gene expression profiles had defined 5 molecular subtypes based on certain intrinsic genes. This study aimed to evaluate the prediction consistency of breast cancer molecular subtypes from 3 distinct intrinsic gene sets (Sørlie 500, Hu 306 and PAM50 as well as clinical presentations of each molecualr subtype in Han Chinese population. Methods In all, 169 breast cancer samples (44 from Taiwan and 125 from China of Han Chinese population were gathered, and the gene expression features corresponding to 3 distinct intrinsic gene sets (Sørlie 500, Hu 306 and PAM50 were retrieved for molecular subtype prediction. Results For Sørlie 500 and Hu 306 intrinsic gene set, mean-centring of genes and distance-weighted discrimination (DWD remarkably reduced the number of unclassified cases. Regarding pairwise agreement, the highest predictive consistency was found between Hu 306 and PAM50. In all, 150 and 126 samples were assigned into identical subtypes by both Hu 306 and PAM50 genes, under mean-centring and DWD. Luminal B tended to show a higher nuclear grade and have more HER2 over-expression status than luminal A did. No basal-like breast tumours were ER positive, and most HER2-enriched breast tumours showed HER2 over-expression, whereas, only two-thirds of ER negativity/HER2 over-expression tumros were predicted as HER2-enriched molecular subtype. For 44 Taiwanese breast cancers with survival data, a better prognosis of luminal A than luminal B subtype in ER-postive breast cancers and a better prognosis of basal-like than HER2-enriched subtype in ER-negative breast cancers was observed. Conclusions We suggest that the intrinsic signature Hu 306 or PAM50 be used for breast cancers in the Han Chinese population during molecular subtyping. For the prognostic value and decision making based on intrinsic subtypes, further prospective

  18. Immunohistochemical Expression of Survivin in Breast Carcinoma: Relationship with Clinico pathological Parameters, Proliferation and Molecular Classification

    International Nuclear Information System (INIS)

    YOUSSEF, N.S.; HEWEDI, I.H.; ABD RABOH, N.M.

    2008-01-01

    Background and Objective: Survivin is a novel member of the inhibitor of apoptosis (IAP) gene family. It is associated with more aggressive behavior and parameters of poor prognosis in most human cancers including gastric, colorectal and bladder carcinomas. However, conflicting data exist on its prognostic effect in breast cancer. This current study is designed to assess survivin expression in breast carcinoma relating results with clinico pathological parameters, proliferation (MIB-1) and molecular classification. Material and Methods: Our retrospective study com- prised of 65 archived cases of breast carcinoma. Samples from the tumor and the adjacent normal breast tissue were immuno stained for survivin and MIB-1. Nuclear and cytoplasmic survivin expression was evaluated in normal breast tissue and carcinoma regarding both the intensity and the percentage of positive cells. ER, PR, HER2 were used as surrogate markers to classify the cases into four molecular subtypes. Results: Survivin expression was detected in 78.5% of breast carcinomas. The adjacent normal breast tissue was immuno negative. Survivin expression showed significant association with increased tumor size ( p <0.0001), high histologic grade ( p =0.04), lymph node metastases ( p <0.001), advanced tumor stage ( p <0.0001), MIB-1 expression ( p =0.02), negative estrogen receptor status ( p =0.01) and negative progesterone receptor status ( p <0.0001). The subcellular localization of survivin significantly related to histologic grade, stage and lymph node involvement. The percentage of TNP (triple negative phenotype) and HER2+/ER-PR- tumors expressing survivin were significantly higher compared to the Luminal subtypes ( p =0.01). Conclusion: Survivin expression was associated with parameters of poor prognosis in breast cancer. Moreover, the cancer-specific expression of survivin, coupled with its importance in inhibiting cell death and in regulating cell division, makes it a potential target for novel

  19. Baseline staging tests based on molecular subtype is necessary for newly diagnosed breast cancer.

    Science.gov (United States)

    Chen, Xuesong; Sun, Lichun; Cong, Yingying; Zhang, Tingting; Lin, Qiushi; Meng, Qingwei; Pang, Hui; Zhao, Yanbin; Li, Yu; Cai, Li; Dong, Xiaoqun

    2014-03-17

    Bone scanning (BS), liver ultrasonography (LUS), and chest radiography (CXR) are commonly recommended for baseline staging in patients with newly diagnosed breast cancer. The purpose of this study is to demonstrate whether these tests are indicated for specific patient subpopulation based on clinical staging and molecular subtype. A retrospective study on 5406 patients with newly diagnosed breast cancer was conducted to identify differences in occurrence of metastasis based on clinical staging and molecular subtypes. All patients had been evaluated by BS, LUS and CXR at diagnosis. Complete information on clinical staging was available in 5184 patients. For stage I, II, and III, bone metastasis rate was 0%, 0.6% and 2.7%, respectively (P diagnosed breast cancer.

  20. 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

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

    NARCIS (Netherlands)

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

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

  2. Molecular Mechanisms of Breast Cancer Metastasis and Potential Anti-metastatic Compounds.

    Science.gov (United States)

    Tungsukruthai, Sucharat; Petpiroon, Nalinrat; Chanvorachote, Pithi

    2018-05-01

    Throughout the world, breast cancer is among the major causes of cancer-related death and is the most common cancer found in women. The development of cancer molecular knowledge has surpassed the novel concept of cancer biology and unraveled principle targets for anticancer drug developments and treatment strategies. Metastatic breast cancer cells acquire their aggressive features through several mechanisms, including augmentation of survival, proliferation, tumorigenicity, and motility-related cellular pathways. Clearly, natural product-derived compounds have since long been recognized as an important source for anticancer drugs, several of which have been shown to have promising anti-metastasis activities by suppressing key molecular features supporting such cell aggressiveness. This review provides the essential details of breast cancer, the molecular-based insights into metastasis, as well as the effects and mechanisms of potential compounds for breast cancer therapeutic approaches. As the abilities of cancer cells to invade and metastasize are addressed as the hallmarks of cancer, compounds possessing anti-metastatic effects, together with their defined molecular drug action could benefit the development of new drugs as well as treatment strategies. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  3. Advances in the Molecular Analysis of Breast Cancer: Pathway Toward Personalized Medicine.

    Science.gov (United States)

    Rosa, Marilin

    2015-04-01

    Breast cancer is a heterogeneous disease that encompasses a wide range of clinical behaviors and histological and molecular variants. It is the most common type of cancer affecting women worldwide and is the second leading cause of cancer death. A comprehensive literature search was performed to explore the advances in molecular medicine related to the diagnosis and treatment of breast cancer. During the last few decades, advances in molecular medicine have changed the landscape of cancer treatment as new molecular tests complement and, in many instances, exceed traditional methods for determining patient prognosis and response to treatment options. Personalized medicine is becoming the standard of care around the world. Developments in molecular profiling, genomic analysis, and the discovery of targeted drug therapies have significantly improved patient survival rates and quality of life. This review highlights what pathologists need to know about current molecular tests for classification and prognostic/ predictive assessment of breast carcinoma as well as their role as part of the medical team.

  4. Molecular Modification of Metadherin/MTDH Impacts the Sensitivity of Breast Cancer to Doxorubicin.

    Directory of Open Access Journals (Sweden)

    Zhenchuan Song

    Full Text Available Breast cancer is a leading cause of death in women and with an increasing worldwide incidence. Doxorubicin, as a first-line anthracycline-based drug is conventional used on breast cancer clinical chemotherapy. However, the drug resistances limited the curative effect of the doxorubicin therapy in breast cancer patients, but the molecular mechanism determinants of breast cancer resistance to doxorubicin chemotherapy are not fully understood. In order to explore the association between metadherin (MTDH and doxorubicin sensitivity, the differential expressions of MTDH in breast cancer cell lines and the sensitivity to doxorubicin of breast cancer cell lines were investigated.The mRNA and protein expression of MTDH were determined by real-time PCR and Western blot in breast cancer cells such as MDA-MB-231, MCF-7, MDA-MB-435S, MCF-7/ADR cells. Once MTDH gene was knocked down by siRNA in MCF-7/ADR cells and overexpressed by MTDH plasmid transfection in MDA-MB-231 cells, the cell growth and therapeutic sensitivity of doxorubicin were evaluated using MTT and the Cell cycle assay and apoptosis rate was determined by flow cytometry.MCF-7/ADR cells revealed highly expressed MTDH and MDA-MB-231 cells had the lowest expression of MTDH. After MTDH gene was knocked down, the cell proliferation was inhibited, and the inhibitory rate of cell growth and apoptosis rate were enhanced, and the cell cycle arrest during the G0/G1 phase in the presence of doxorubicin treatment. On the other hand, the opposite results were observed in MDA-MB-231 cells with overexpressed MTDH gene.MTDH gene plays a promoting role in the proliferation of breast cancer cells and its high expression may be associated with doxorubicin sensitivity of breast cancer.

  5. Molecular Effects of Doxorubicin on Choline Metabolism in Breast Cancer

    Directory of Open Access Journals (Sweden)

    Menglin Cheng

    2017-08-01

    Full Text Available Abnormal choline phospholipid metabolism is a hallmark of cancer. The magnetic resonance spectroscopy (MRS detected total choline (tCho signal can serve as an early noninvasive imaging biomarker of chemotherapy response in breast cancer. We have quantified the individual components of the tCho signal, glycerophosphocholine (GPC, phosphocholine (PC and free choline (Cho, before and after treatment with the commonly used chemotherapeutic drug doxorubicin in weakly metastatic human MCF7 and triple-negative human MDA-MB-231 breast cancer cells. While the tCho concentration did not change following doxorubicin treatment, GPC significantly increased and PC decreased. Of the two phosphatidylcholine-specific PLD enzymes, only PLD1, but not PLD2, mRNA was down-regulated by doxorubicin treatment. For the two reported genes encoding GPC phosphodiesterase, the mRNA of GDPD6, but not GDPD5, decreased following doxorubicin treatment. mRNA levels of choline kinase α (ChKα, which converts Cho to PC, were reduced following doxorubicin treatment. PLD1 and ChKα protein levels decreased following doxorubicin treatment in a concentration dependent manner. Treatment with the PLD1 specific inhibitor VU0155069 sensitized MCF7 and MDA-MB-231 breast cancer cells to doxorubicin-induced cytotoxicity. Low concentrations of 100 nM of doxorubicin increased MDA-MB-231 cell migration. GDPD6, but not PLD1 or ChKα, silencing by siRNA abolished doxorubicin-induced breast cancer cell migration. Doxorubicin induced GPC increase and PC decrease are caused by reductions in PLD1, GDPD6, and ChKα mRNA and protein expression. We have shown that silencing or inhibiting these genes/proteins can promote drug effectiveness and reduce adverse drug effects. Our findings emphasize the importance of detecting PC and GPC individually.

  6. Tryptophan metabolism in breast cancers: molecular imaging and immunohistochemistry studies

    International Nuclear Information System (INIS)

    Juhász, Csaba; Nahleh, Zeina; Zitron, Ian; Chugani, Diane C.; Janabi, Majid Z.; Bandyopadhyay, Sudeshna; Ali-Fehmi, Rouba; Mangner, Thomas J.; Chakraborty, Pulak K.; Mittal, Sandeep; Muzik, Otto

    2012-01-01

    Introduction: Tryptophan oxidation via the kynurenine pathway is an important mechanism of tumoral immunoresistance. Increased tryptophan metabolism via the serotonin pathway has been linked to malignant progression in breast cancer. In this study, we combined quantitative positron emission tomography (PET) with tumor immunohistochemistry to analyze tryptophan transport and metabolism in breast cancer. Methods: Dynamic α-[ 11 C]methyl-L-tryptophan (AMT) PET was performed in nine women with stage II–IV breast cancer. PET tracer kinetic modeling was performed in all tumors. Expression of L-type amino acid transporter 1 (LAT1), indoleamine 2,3-dioxygenase (IDO; the initial and rate-limiting enzyme of the kynurenine pathway) and tryptophan hydroxylase 1 (TPH1; the initial enzyme of the serotonin pathway) was assessed by immunostaining of resected tumor specimens. Results: Tumor AMT uptake peaked at 5–20 min postinjection in seven tumors; the other two cases showed protracted tracer accumulation. Tumor standardized uptake values (SUVs) varied widely (2.6–9.8) and showed a strong positive correlation with volume of distribution values derived from kinetic analysis (P < .01). Invasive ductal carcinomas (n = 6) showed particularly high AMT SUVs (range, 4.7–9.8). Moderate to strong immunostaining for LAT1, IDO and TPH1 was detected in most tumor cells. Conclusions: Breast cancers show differential tryptophan kinetics on dynamic PET. SUVs measured 5–20 min postinjection reflect reasonably the tracer's volume of distribution. Further studies are warranted to determine if in vivo AMT accumulation in these tumors is related to tryptophan metabolism via the kynurenine and serotonin pathways.

  7. Clinical and molecular characterization of BRCA-associated breast cancer

    DEFF Research Database (Denmark)

    Soenderstrup, I. M.H.; Laenkholm, A. V.; Jensen, M. B.

    2018-01-01

    Background: In breast cancer (BC) patients a cancer predisposing BRCA1/2 mutation is associated with adverse tumor characteristics, risk assessment and treatment allocation. We aimed to estimate overall- (OS) and disease-free survival (DFS) according to tumor characteristics and treatment among...... women who within two years of definitive surgery for primary BC were shown to carry a mutation in BRCA1/2 . Material and methods: From the clinical database of the Danish Breast Cancer Group we included 141 BRCA1 and 96 BRCA2 BC patients. Estrogen receptor and HER2 status were centrally reviewed......–81). Ten-year OS and DFS for BRCA2 BC were 88% (95% CI 78–94) and 84% (95% CI 74–91). BRCA1 BC patients as compared to BRCA2 BC patients had a higher risk of BC relapse or non-breast cancer within ten years of follow-up, independent of ER status (adjusted HR 2.78 95% CI 1.28–6.05, p = .01), but BRCA...

  8. Quantitative background parenchymal uptake on molecular breast imaging and breast cancer risk: a case-control study.

    Science.gov (United States)

    Hruska, Carrie B; Geske, Jennifer R; Swanson, Tiffinee N; Mammel, Alyssa N; Lake, David S; Manduca, Armando; Conners, Amy Lynn; Whaley, Dana H; Scott, Christopher G; Carter, Rickey E; Rhodes, Deborah J; O'Connor, Michael K; Vachon, Celine M

    2018-06-05

    Background parenchymal uptake (BPU), which refers to the level of Tc-99m sestamibi uptake within normal fibroglandular tissue on molecular breast imaging (MBI), has been identified as a breast cancer risk factor, independent of mammographic density. Prior analyses have used subjective categories to describe BPU. We evaluate a new quantitative method for assessing BPU by testing its reproducibility, comparing quantitative results with previously established subjective BPU categories, and determining the association of quantitative BPU with breast cancer risk. Two nonradiologist operators independently performed region-of-interest analysis on MBI images viewed in conjunction with corresponding digital mammograms. Quantitative BPU was defined as a unitless ratio of the average pixel intensity (counts/pixel) within the fibroglandular tissue versus the average pixel intensity in fat. Operator agreement and the correlation of quantitative BPU measures with subjective BPU categories assessed by expert radiologists were determined. Percent density on mammograms was estimated using Cumulus. The association of quantitative BPU with breast cancer (per one unit BPU) was examined within an established case-control study of 62 incident breast cancer cases and 177 matched controls. Quantitative BPU ranged from 0.4 to 3.2 across all subjects and was on average higher in cases compared to controls (1.4 versus 1.2, p Quantitative BPU was strongly correlated with subjective BPU categories (Spearman's r = 0.59 to 0.69, p quantitative BPU measure, assessed by intraclass correlation, was 0.92 and 0.98, respectively. Quantitative BPU measures showed either no correlation or weak negative correlation with mammographic percent density. In a model adjusted for body mass index and percent density, higher quantitative BPU was associated with increased risk of breast cancer for both operators (OR = 4.0, 95% confidence interval (CI) 1.6-10.1, and 2.4, 95% CI 1.2-4.7). Quantitative

  9. Molecular Mechanisms of Metastasis Suppression in Human Breast Cancer

    Science.gov (United States)

    1997-07-01

    immune system? Ann N Y Acad Sci, JR, 1986, The role of NK cells in tumour growth and 741, 212-15. metastasis in beige mice. Nature, 284, 622-4. 89. Stone ...77. Simmons ML and Brick JO, 1969, The Laboratory 96. Senger DR, Brown LF, Claffey KP and Dvorak HF, Mouse. Hollaender A, ed. Englewood Cliffs, NJ...ranfe of huan tumo sme I I su ding the human chromosome 11 into the highly metastatic MDA-MB-435 breast tumorigenic phenotype of several tumor lines

  10. Integration of a Radiosensitivity Molecular Signature Into the Assessment of Local Recurrence Risk in Breast Cancer

    International Nuclear Information System (INIS)

    Torres-Roca, Javier F.; Fulp, William J.; Caudell, Jimmy J.; Servant, Nicolas; Bollet, Marc A.; Vijver, Marc van de; Naghavi, Arash O.; Harris, Eleanor E.; Eschrich, Steven A.

    2015-01-01

    Purpose: Recently, we developed radiosensitivity (RSI), a clinically validated molecular signature that estimates tumor radiosensitivity. In the present study, we tested whether integrating RSI with the molecular subtype refines the classification of local recurrence (LR) risk in breast cancer. Methods and Materials: RSI and molecular subtype were evaluated in 343 patients treated with breast-conserving therapy that included whole-breast radiation therapy with or without a tumor bed boost (dose range 45-72 Gy). The follow-up period for patients without recurrence was 10 years. The clinical endpoint was LR-free survival. Results: Although RSI did not uniformly predict for LR across the entire cohort, combining RSI and the molecular subtype identified a subpopulation with an increased risk of LR: triple negative (TN) and radioresistant (reference TN-radioresistant, hazard ratio [HR] 0.37, 95% confidence interval [CI] 0.15-0.92, P=.02). TN patients who were RSI-sensitive/intermediate had LR rates similar to those of luminal (LUM) patients (HR 0.86, 95% CI 0.47-1.57, P=.63). On multivariate analysis, combined RSI and molecular subtype (P=.004) and age (P=.001) were the most significant predictors of LR. In contrast, integrating RSI into the LUM subtype did not identify additional risk groups. We hypothesized that radiation dose escalation was affecting radioresistance in the LUM subtype and serving as a confounder. An increased radiation dose decreased LR only in the luminal-resistant (LUM-R) subset (HR 0.23, 95% CI 0.05-0.98, P=.03). On multivariate analysis, the radiation dose was an independent variable only in the LUMA/B-RR subset (HR 0.025, 95% CI 0.001-0.946, P=.046), along with age (P=.008), T stage (P=.004), and chemotherapy (P=.008). Conclusions: The combined molecular subtype–RSI identified a novel molecular subpopulation (TN and radioresistant) with an increased risk of LR after breast-conserving therapy. We propose that the combination of RSI and

  11. Integration of a Radiosensitivity Molecular Signature Into the Assessment of Local Recurrence Risk in Breast Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Torres-Roca, Javier F., E-mail: javier.torresroca@moffitt.org [Department of Radiation Oncology, Moffitt Cancer Center, Tampa, Florida (United States); Department of Chemical Biology and Molecular Medicine, Moffitt Cancer Center, Tampa, Florida (United States); Fulp, William J. [Department of Bioinformatics, Moffitt Cancer Center, Tampa, Florida (United States); Department of Biostatistics, Moffitt Cancer Center, Tampa, Florida (United States); Caudell, Jimmy J. [Department of Radiation Oncology, Moffitt Cancer Center, Tampa, Florida (United States); Servant, Nicolas [Institut Curie, INSERM U900, Paris (France); Mines ParisTech, Paris (France); Bollet, Marc A. [Institut Curie, INSERM U900, Paris (France); Vijver, Marc van de [Netherlands Cancer Institute, Amsterdam (Netherlands); Naghavi, Arash O. [Department of Radiation Oncology, Moffitt Cancer Center, Tampa, Florida (United States); Harris, Eleanor E. [East Carolina University, Greensborough, North Carolina (United States); Eschrich, Steven A. [Department of Bioinformatics, Moffitt Cancer Center, Tampa, Florida (United States)

    2015-11-01

    Purpose: Recently, we developed radiosensitivity (RSI), a clinically validated molecular signature that estimates tumor radiosensitivity. In the present study, we tested whether integrating RSI with the molecular subtype refines the classification of local recurrence (LR) risk in breast cancer. Methods and Materials: RSI and molecular subtype were evaluated in 343 patients treated with breast-conserving therapy that included whole-breast radiation therapy with or without a tumor bed boost (dose range 45-72 Gy). The follow-up period for patients without recurrence was 10 years. The clinical endpoint was LR-free survival. Results: Although RSI did not uniformly predict for LR across the entire cohort, combining RSI and the molecular subtype identified a subpopulation with an increased risk of LR: triple negative (TN) and radioresistant (reference TN-radioresistant, hazard ratio [HR] 0.37, 95% confidence interval [CI] 0.15-0.92, P=.02). TN patients who were RSI-sensitive/intermediate had LR rates similar to those of luminal (LUM) patients (HR 0.86, 95% CI 0.47-1.57, P=.63). On multivariate analysis, combined RSI and molecular subtype (P=.004) and age (P=.001) were the most significant predictors of LR. In contrast, integrating RSI into the LUM subtype did not identify additional risk groups. We hypothesized that radiation dose escalation was affecting radioresistance in the LUM subtype and serving as a confounder. An increased radiation dose decreased LR only in the luminal-resistant (LUM-R) subset (HR 0.23, 95% CI 0.05-0.98, P=.03). On multivariate analysis, the radiation dose was an independent variable only in the LUMA/B-RR subset (HR 0.025, 95% CI 0.001-0.946, P=.046), along with age (P=.008), T stage (P=.004), and chemotherapy (P=.008). Conclusions: The combined molecular subtype–RSI identified a novel molecular subpopulation (TN and radioresistant) with an increased risk of LR after breast-conserving therapy. We propose that the combination of RSI and

  12. Molecular Heterogeneity in Primary Breast Carcinomas and Axillary Lymph Node Metastases Assessed by Genomic Fingerprinting Analysis

    Science.gov (United States)

    Ellsworth, Rachel E; Toro, Allyson L; Blackburn, Heather L; Decewicz, Alisha; Deyarmin, Brenda; Mamula, Kimberly A; Costantino, Nicholas S; Hooke, Jeffrey A; Shriver, Craig D; Ellsworth, Darrell L

    2015-01-01

    Molecular heterogeneity within primary breast carcinomas and among axillary lymph node (LN) metastases may impact diagnosis and confound treatment. In this study, we used short tandem repeated sequences to assess genomic heterogeneity and to determine hereditary relationships among primary tumor areas and regional metastases from 30 breast cancer patients. We found that primary carcinomas were genetically heterogeneous and sampling multiple areas was necessary to adequately assess genomic variability. LN metastases appeared to originate at different time periods during disease progression from different sites of the primary tumor and the extent of genomic divergence among regional metastases was associated with a less favorable patient outcome (P = 0.009). In conclusion, metastasis is a complex process influenced by primary tumor heterogeneity and variability in the timing of dissemination. Genomic variation in primary breast tumors and regional metastases may negatively impact clinical diagnostics and contribute to therapeutic resistance. PMID:26279627

  13. Molecular Heterogeneity in Primary Breast Carcinomas and Axillary Lymph Node Metastases Assessed by Genomic Fingerprinting Analysis

    Directory of Open Access Journals (Sweden)

    Rachel E. Ellsworth

    2015-01-01

    Full Text Available Molecular heterogeneity within primary breast carcinomas and among axillary lymph node (LN metastases may impact diagnosis and confound treatment. In this study, we used short tandem repeated sequences to assess genomic heterogeneity and to determine hereditary relationships among primary tumor areas and regional metastases from 30 breast cancer patients. We found that primary carcinomas were genetically heterogeneous and sampling multiple areas was necessary to adequately assess genomic variability. LN metastases appeared to originate at different time periods during disease progression from different sites of the primary tumor and the extent of genomic divergence among regional metastases was associated with a less favorable patient outcome ( P = 0.009. In conclusion, metastasis is a complex process influenced by primary tumor heterogeneity and variability in the timing of dissemination. Genomic variation in primary breast tumors and regional metastases may negatively impact clinical diagnostics and contribute to therapeutic resistance.

  14. Mammary Stem Cells and Breast Cancer Stem Cells: Molecular Connections and Clinical Implications.

    Science.gov (United States)

    Celià-Terrassa, Toni

    2018-05-04

    Cancer arises from subpopulations of transformed cells with high tumor initiation and repopulation ability, known as cancer stem cells (CSCs), which share many similarities with their normal counterparts. In the mammary gland, several studies have shown common molecular regulators between adult mammary stem cells (MaSCs) and breast cancer stem cells (bCSCs). Cell plasticity and self-renewal are essential abilities for MaSCs to maintain tissue homeostasis and regenerate the gland after pregnancy. Intriguingly, these properties are similarly executed in breast cancer stem cells to drive tumor initiation, tumor heterogeneity and recurrence after chemotherapy. In addition, both stem cell phenotypes are strongly influenced by external signals from the microenvironment, immune cells and supportive specific niches. This review focuses on the intrinsic and extrinsic connections of MaSC and bCSCs with clinical implications for breast cancer progression and their possible therapeutic applications.

  15. Revealing the Molecular Portrait of Triple Negative Breast Tumors in an Understudied Population through Omics Analysis of Formalin-Fixed and Paraffin-Embedded Tissues.

    Science.gov (United States)

    Vaca-Paniagua, Felipe; Alvarez-Gomez, Rosa María; Maldonado-Martínez, Hector Aquiles; Pérez-Plasencia, Carlos; Fragoso-Ontiveros, Veronica; Lasa-Gonsebatt, Federico; Herrera, Luis Alonso; Cantú, David; Bargallo-Rocha, Enrique; Mohar, Alejandro; Durand, Geoffroy; Forey, Nathalie; Voegele, Catherine; Vallée, Maxime; Le Calvez-Kelm, Florence; McKay, James; Ardin, Maude; Villar, Stéphanie; Zavadil, Jiri; Olivier, Magali

    2015-01-01

    Triple negative breast cancer (TNBC), defined by the lack of expression of the estrogen receptor, progesterone receptor and human epidermal receptor 2, is an aggressive form of breast cancer that is more prevalent in certain populations, in particular in low- and middle-income regions. The detailed molecular features of TNBC in these regions remain unexplored as samples are mostly accessible as formalin-fixed paraffin embedded (FFPE) archived tissues, a challenging material for advanced genomic and transcriptomic studies. Using dedicated reagents and analysis pipelines, we performed whole exome sequencing and miRNA and mRNA profiling of 12 FFPE tumor tissues collected from pathological archives in Mexico. Sequencing analyses of the tumor tissues and their blood pairs identified TP53 and RB1 genes as the most frequently mutated genes, with a somatic mutation load of 1.7 mutations/exome Mb on average. Transcriptional analyses revealed an overexpression of growth-promoting signals (EGFR, PDGFR, VEGF, PIK3CA, FOXM1), a repression of cell cycle control pathways (TP53, RB1), a deregulation of DNA-repair pathways, and alterations in epigenetic modifiers through miRNA:mRNA network de-regulation. The molecular programs identified were typical of those described in basal-like tumors in other populations. This work demonstrates the feasibility of using archived clinical samples for advanced integrated genomics analyses. It thus opens up opportunities for investigating molecular features of tumors from regions where only FFPE tissues are available, allowing retrospective studies on the search for treatment strategies or on the exploration of the geographic diversity of breast cancer.

  16. [Molecular classification of breast cancer patients obtained through the technique of chromogenic in situ hybridization (CISH)].

    Science.gov (United States)

    Fernández, Angel; Reigosa, Aldo

    2013-12-01

    Breast cancer is a heterogeneous disease composed of a growing number of biological subtypes, with substantial variability of the disease progression within each category. The aim of this research was to classify the samples object of study according to the molecular classes of breast cancer: luminal A, luminal B, HER2 and triple negative, as a result of the state of HER2 amplification obtained by the technique of chromogenic in situ hybridization (CISH). The sample consisted of 200 biopsies fixed in 10% formalin, processed by standard techniques up to paraffin embedding, corresponding to patients diagnosed with invasive ductal carcinoma of the breast. These biopsies were obtained from patients from private practice and the Institute of Oncology "Dr. Miguel Pérez Carreño", for immunohistochemistry (IHC) of hormone receptors and HER2 made in the Hospital Metropolitano del Norte, Valencia, Venezuela. The molecular classification of the patient's tumors considering the expression of estrogen and progesterone receptors by IHC and HER2 amplification by CISH, allowed those cases originally classified as unknown, since they had an indeterminate (2+) outcome for HER2 expression by IHC, to be grouped into the different molecular classes. Also, this classification permitted that some cases, initially considered as belonging to a molecular class, were assigned to another class, after the revaluation of the HER2 status by CISH.

  17. Novel Molecular Markers of Malignancy in Histologically Normal and Benign Breast

    Directory of Open Access Journals (Sweden)

    Aejaz Nasir

    2011-01-01

    Full Text Available To detect the molecular changes of malignancy in histologically normal breast (HNB tissues, we recently developed a novel 117-gene-malignancy-signature. Here we report validation of our leading malignancy-risk-genes, topoisomerase-2-alpha (TOP2A, minichromosome-maintenance-protein-2 (MCM2 and “budding-uninhibited-by-benzimidazoles-1-homolog-beta” (BUB1B at the protein level. Using our 117-gene malignancy-signature, we classified 18 fresh-frozen HNB tissues from 18 adult female breast cancer patients into HNB-tissues with low-grade (HNB-LGMA; =9 and high-grade molecular abnormality (HNB-HGMA; =9. Archival sections of additional HNB tissues from these patients, and invasive ductal carcinoma (IDC tissues from six other patients were immunostained for these biomarkers. TOP2A/MCM2 expression was assessed as staining index (% and BUB1B expression as H-scores (0–300. Increasing TOP2A, MCM2, and BUB1B protein expression from HNB-LGMA to HNB-HGMA tissues to IDCs validated our microarray-based molecular classification of HNB tissues by immunohistochemistry. We also demonstrated an increasing expression of TOP2A protein on an independent test set of HNB/benign/reductionmammoplasties, atypical-ductal-hyperplasia with and without synchronous breast cancer, DCIS and IDC tissues using a custom tissue microarray (TMA. In conclusion, TOP2A, MCM2, and BUB1B proteins are potential molecular biomarkers of malignancy in histologically normal and benign breast tissues. Larger-scale clinical validation studies are needed to further evaluate the clinical utility of these molecular biomarkers.

  18. Musculoskeletal MRI: dedicated systems

    International Nuclear Information System (INIS)

    Masciocchi, C.; Barile, A.; Satragno, L.

    2000-01-01

    The ''dedicated'' MRI units have characteristics of high diagnostic accuracy and lower installation and management costs as compared with whole-body systems. The dedicated MRI units are easy to install. The low weight allows their installation also under unfavorable circumstances. In a dedicated system cost-effectiveness and ease of installation must be accompanied by the capability of providing high-quality images. In our experience, the high number of examinations performed, the most part of which provided with the surgical controls, allowed an accurate evaluation of the diagnostic potentialities of the dedicated magnet. We were not able to perform the examinations in only 3 % of cases due to the physical shape of the patient and the clinical condition of the patient which may hinder the correct positioning of the limb. The overlapping of the diagnostic accuracy of the E-scan and Artoscan units in the study of the lower limbs, compared with whole-body units and surgery, prompted us to exploit the potentialities of the E-Scan in the study of the shoulder. We had a good correlation between E-Scan, whole-body units, and surgical findings, which confirmed the high diagnostic accuracy of the dedicated system. In conclusion, in our experience carried out in the musculoskeletal system, the dedicated magnets showed promising results. Their diagnostic reliability and utility was comparable to that obtained from conventional units operating at higher magnetic fields. (orig.)

  19. Proteomics Characterization of the Molecular Mechanisms of Mutant P53 Reactivation with PRIMA-1 in Breast Cancer Cells

    National Research Council Canada - National Science Library

    Daoud, Sayed S

    2006-01-01

    The main purpose of the study is to identify novel protein-protein interactions in various locations of cells to establish the molecular mechanisms of mutant p53 reactivation with PRIMA-1 in breast cancer cells...

  20. Integrated Molecular Imaging and Therapy for Breast Cancer

    National Research Council Canada - National Science Library

    Panchapakesan, Balaji

    2008-01-01

    ...) and NIR dosing of cancer cells using SWCNT. While previous studies have shown the transport of DNA into cells using nanotubes, in this study we show multi-component molecular targeting of both IGF1R and Her2 surface markers in cancer cells...

  1. Molecular Epidemiology of Breast Cancer: Establishment of an at Risk Cohort and Methods to Improve the Collection and Use of Risk Factor Data

    National Research Council Canada - National Science Library

    Johnson, Christine

    1997-01-01

    The aim of the research program we are developing is to define molecular markers and their interaction with other risk factors as risk indicators for development of breast cancer among women with benign breast disease (BBD...

  2. Molecular biology of breast cancer metastasis: Genetic regulation of human breast carcinoma metastasis

    International Nuclear Information System (INIS)

    Welch, Danny R; Steeg, Patricia S; Rinker-Schaeffer, Carrie W

    2000-01-01

    The present is an overview of recent data that describes the genetic underpinnings of the suppression of cancer metastasis. Despite the explosion of new information about the genetics of cancer, only six human genes have thus far been shown to suppress metastasis functionally. Not all have been shown to be functional in breast carcinoma. Several additional genes inhibit various steps of the metastatic cascade, but do not necessarily block metastasis when tested using in vivo assays. The implications of this are discussed. Two recently discovered metastasis suppressor genes block proliferation of tumor cells at a secondary site, offering a new target for therapeutic intervention

  3. Molecular Features of Subtype-Specific Progression from Ductal Carcinoma In Situ to Invasive Breast Cancer

    Directory of Open Access Journals (Sweden)

    Robert Lesurf

    2016-07-01

    Full Text Available Breast cancer consists of at least five main molecular “intrinsic” subtypes that are reflected in both pre-invasive and invasive disease. Although previous studies have suggested that many of the molecular features of invasive breast cancer are established early, it is unclear what mechanisms drive progression and whether the mechanisms of progression are dependent or independent of subtype. We have generated mRNA, miRNA, and DNA copy-number profiles from a total of 59 in situ lesions and 85 invasive tumors in order to comprehensively identify those genes, signaling pathways, processes, and cell types that are involved in breast cancer progression. Our work provides evidence that there are molecular features associated with disease progression that are unique to the intrinsic subtypes. We additionally establish subtype-specific signatures that are able to identify a small proportion of pre-invasive tumors with expression profiles that resemble invasive carcinoma, indicating a higher likelihood of future disease progression.

  4. Molecular profiling of advanced breast cancer tumors is beneficial in assisting clinical treatment plans.

    Science.gov (United States)

    Carter, Philip; Alifrangis, Costi; Cereser, Biancastella; Chandrasinghe, Pramodh; Del Bel Belluz, Lisa; Moderau, Nina; Poyia, Fotini; Schwartzberg, Lee S; Tabassum, Neha; Wen, Jinrui; Krell, Jonathan; Stebbing, Justin

    2018-04-03

    We used data obtained by Caris Life Sciences, to evaluate the benefits of tailoring treatments for a breast carcinoma cohort by using tumor molecular profiles to inform decisions. Data for 92 breast cancer patients from the commercial Caris Molecular Intelligence database was retrospectively divided into two groups, so that the first always followed treatment recommendations, whereas in the second group all patients received at least one drug after profiling that was predicted to lack benefit. The biomarker and drug associations were based on tests including fluorescent in situ hybridization and DNA sequencing, although immunohistochemistry was the main test used. Patients whose drugs matched those recommended according to their tumor profile had an average overall survival of 667 days, compared to 510 days for patients that did not (P=0.0316). In the matched treatment group, 26% of patients were deceased by the last time of monitoring, whereas this was 41% in the unmatched group (P=0.1257). We therefore confirm the ability of tumor molecular profiling to improve survival of breast cancer patients. Immunohistochemistry biomarkers for the androgen, estrogen and progesterone receptors were found to be prognostic for survival.

  5. Molecular portrait of breast cancer in China reveals comprehensive transcriptomic likeness to Caucasian breast cancer and low prevalence of luminal A subtype

    International Nuclear Information System (INIS)

    Huang, Xiaoyan; Dugo, Matteo; Callari, Maurizio; Sandri, Marco; De Cecco, Loris; Valeri, Barbara; Carcangiu, Maria Luisa; Xue, Jingyan; Bi, Rui; Veneroni, Silvia; Daidone, Maria Grazia; Ménard, Sylvie; Tagliabue, Elda; Shao, Zhimin; Wu, Jiong; Orlandi, Rosaria

    2015-01-01

    The recent dramatic increase in breast cancer incidence across China with progressive urbanization and economic development has signaled the urgent need for molecular and clinical detailing of breast cancer in the Chinese population. Our analyses of a unique transethnic collection of breast cancer frozen specimens from Shanghai Fudan Cancer Center (Chinese Han) profiled simultaneously with an analogous Caucasian Italian series revealed consistent transcriptomic data lacking in batch effects. The prevalence of Luminal A subtype was significantly lower in Chinese series, impacting the overall prevalence of estrogen receptor (ER)-positive disease in a large cohort of Chinese/Caucasian patients. Unsupervised and supervised comparison of gene and microRNA (miRNA) profiles of Chinese and Caucasian samples revealed extensive similarity in the comprehensive taxonomy of transcriptional elements regulating breast cancer biology. Partition of gene expression data using gene lists relevant to breast cancer as “intrinsic” and “extracellular matrix” genes identified Chinese and Caucasian subgroups with equivalent global gene and miRNA profiles. These findings indicate that in the Chinese and Caucasian groups, breast neoplasia and the surrounding stromal characteristics undergo the same differentiation and molecular processes. Transcriptional similarity across transethnic cohorts may simplify translational medicine approaches and clinical management of breast cancer patients worldwide

  6. Molecular characterization of breast cancer cell lines through multiple omic approaches.

    Science.gov (United States)

    Smith, Shari E; Mellor, Paul; Ward, Alison K; Kendall, Stephanie; McDonald, Megan; Vizeacoumar, Frederick S; Vizeacoumar, Franco J; Napper, Scott; Anderson, Deborah H

    2017-06-05

    Breast cancer cell lines are frequently used as model systems to study the cellular properties and biology of breast cancer. Our objective was to characterize a large, commonly employed panel of breast cancer cell lines obtained from the American Type Culture Collection (ATCC 30-4500 K) to enable researchers to make more informed decisions in selecting cell lines for specific studies. Information about these cell lines was obtained from a wide variety of sources. In addition, new information about cellular pathways that are activated within each cell line was generated. We determined key protein expression data using immunoblot analyses. In addition, two analyses on serum-starved cells were carried out to identify cellular proteins and pathways that are activated in these cells. These analyses were performed using a commercial PathScan array and a novel and more extensive phosphopeptide-based kinome analysis that queries 1290 phosphorylation events in major signaling pathways. Data about this panel of breast cancer cell lines was also accessed from several online sources, compiled and summarized for the following areas: molecular classification, mRNA expression, mutational status of key proteins and other possible cancer-associated mutations, and the tumorigenic and metastatic capacity in mouse xenograft models of breast cancer. The cell lines that were characterized included 10 estrogen receptor (ER)-positive, 12 human epidermal growth factor receptor 2 (HER2)-amplified and 18 triple negative breast cancer cell lines, in addition to 4 non-tumorigenic breast cell lines. Within each subtype, there was significant genetic heterogeneity that could impact both the selection of model cell lines and the interpretation of the results obtained. To capture the net activation of key signaling pathways as a result of these mutational combinations, profiled pathway activation status was examined. This provided further clarity for which cell lines were particularly deregulated

  7. Analysis of molecular markers as predictive factors of lymph node involvement in breast carcinoma.

    Science.gov (United States)

    Paula, Luciana Marques; De Moraes, Luis Henrique Ferreira; Do Canto, Abaeté Leite; Dos Santos, Laurita; Martin, Airton Abrahão; Rogatto, Silvia Regina; De Azevedo Canevari, Renata

    2017-01-01

    Nodal status is the most significant independent prognostic factor in breast cancer. Identification of molecular markers would allow stratification of patients who require surgical assessment of lymph nodes from the large numbers of patients for whom this surgical procedure is unnecessary, thus leading to a more accurate prognosis. However, up to now, the reported studies are preliminary and controversial, and although hundreds of markers have been assessed, few of them have been used in clinical practice for treatment or prognosis in breast cancer. The purpose of the present study was to determine whether protein phosphatase Mg2+/Mn2+ dependent 1D, β-1,3-N-acetylglucosaminyltransferase, neural precursor cell expressed, developmentally down-regulated 9, prohibitin, phosphoinositide-3-kinase regulatory subunit 5 (PIK3R5), phosphatidylinositol-5-phosphate 4-kinase type IIα, TRF1-interacting ankyrin-related ADP-ribose polymerase 2, BCL2 associated agonist of cell death, G2 and S-phase expressed 1 and PAX interacting protein 1 genes, described as prognostic markers in breast cancer in a previous microarray study, are also predictors of lymph node involvement in breast carcinoma Reverse transcription-quantitative polymerase chain reaction analysis was performed on primary breast tumor tissues from women with negative lymph node involvement (n=27) compared with primary tumor tissues from women with positive lymph node involvement (n=23), and was also performed on primary tumors and paired lymph node metastases (n=11). For all genes analyzed, only the PIK3R5 gene exhibited differential expression in samples of primary tumors with positive lymph node involvement compared with primary tumors with negative lymph node involvement (P=0.0347). These results demonstrate that the PIK3R5 gene may be considered predictive of lymph node involvement in breast carcinoma. Although the other genes evaluated in the present study have been previously characterized to be involved with

  8. A profile of prognostic and molecular factors in European and Māori breast cancer patients

    International Nuclear Information System (INIS)

    Dachs, Gabi U; Wells, J Elisabeth; Robinson, Bridget A; Kano, Maiko; Volkova, Ekaterina; Morrin, Helen R; Davey, Valerie CL; Harris, Gavin C; Cheale, Michelle; Frampton, Christopher; Currie, Margaret J

    2010-01-01

    New Zealand Māori have a poorer outcome from breast cancer than non-Māori, yet prognostic data are sparse. The objective of this study was to quantify levels of prognostic factors in a cohort of self-declared Māori and European breast cancer patients from Christchurch, New Zealand. Clinicopathological and survival data from 337 consecutive breast cancer patients (27 Māori, 310 European) were evaluated. Fewer tumours were high grade in Māori women than European women (p = 0.027). No significant ethnic differences were detected for node status, tumour type, tumour size, human epidermal growth factor receptor, oestrogen and progesterone receptor (ER/PR) status, or survival. In addition, tumour and serum samples from a sub-cohort of 14 Māori matched to 14 NZ European patients were analyzed by immunohistochemistry and enzyme linked immunosorbent assay for molecular prognostic factors. Significant correlations were detected between increased grade and increased levels of hypoxia inducible factor-1 (HIF-1α), glucose transporter-1 (GLUT-1), microvessel density (MVD) and cytokeratins CK5/6 (p < 0.05). High nodal status correlated with reduced carbonic anhydrase IX (CA-IX). Negative ER/PR status correlated with increased GLUT-1, CA-IX and MVD. Within the molecular factors, increased HIF-1α correlated with raised GLUT-1, MVD and CK5/6, and CK5/6 with GLUT-1 and MVD (p < 0.05). The small number of patients in this sub-cohort limited discrimination of ethnic differences. In this Christchurch cohort of breast cancer patients, Māori women were no more likely than European women to have pathological or molecular factors predictive of poor prognosis. These data contrast with data from the North Island NZ, and suggest potential regional differences

  9. MRI and pathological features of different molecular subtypes of breast cancers

    International Nuclear Information System (INIS)

    Yu Yang; Huo Tianlong; Lai Yunyao; Hong Nan

    2014-01-01

    Objective: To investigate the MRI and pathological features of different molecular subtypes of breast cancer. Methods: The data of 202 patients who underwent primary breast cancer resection were retrospectively reviewed. All of the patients had MRI preoperatively. The molecular subtypes of breast cancer defined by immunohistochemistry were classified as basal-like, luminal and HER-2 overexpression. Morphology (including mass or non-mass like enhancement, shape and margin of masses, unifocal or multifocal masses) and enhancement characteristics on MRI, histologic types and grades of tumors were analyzed with Chi-square test, exact test, Fisher exact test, Kruskal-Wallis H test, and Wilcoxon test. Results: Among the 202 patients, 34 were basal-like, 144 were luminal and 24 were HER-2 overexpression. The number of mass cases in each subtype was 29, 133 and 19 respectively,making no significant difference (χ 2 =4.136, P=0.126). As for the shape of basal-like lesions,8 were round,19 were lobular and 2 were irregular, while this distribution was 23, 58, 52 in luminal subtype and 1, 11, 7 in HER-2 overexpression subtype (χ 2 =13.391, P<0.05). The margin was also strikingly different among three groups (smooth, spiculate, irregular): 20, 5, 4 respectively in basal-like, 27, 53, 53 respectively in luminal, and 4, 7, 8 respectively in HER-2 overexpression (χ 2 =28.515, P<0.01). 52.6% (10/19) of HER-2 overexpression cases were multifocal, while only 6.9% (2/29) of luminal and 8.0% (24/133) of basal-like ones were multifocal (χ 2 =16.140, P<0.01). Characteristics in dynamic contrast-enhanced MRI were statistically different, with homogeneous, heterogeneous, and rim enhancement 0, 13, 16 respectively in basal-like cases, 28, 93, 11 respectively in luminal cases and 2, 11, 6 respectively in HER-2 overexpression cases (P<0.01). However, the difference for enhancement curve did not reach significance (P =0.457). Histologic types were significantly different among molecular

  10. Identification of prognostic molecular features in the reactive stroma of human breast and prostate cancer.

    Directory of Open Access Journals (Sweden)

    Anne Planche

    Full Text Available Primary tumor growth induces host tissue responses that are believed to support and promote tumor progression. Identification of the molecular characteristics of the tumor microenvironment and elucidation of its crosstalk with tumor cells may therefore be crucial for improving our understanding of the processes implicated in cancer progression, identifying potential therapeutic targets, and uncovering stromal gene expression signatures that may predict clinical outcome. A key issue to resolve, therefore, is whether the stromal response to tumor growth is largely a generic phenomenon, irrespective of the tumor type or whether the response reflects tumor-specific properties. To address similarity or distinction of stromal gene expression changes during cancer progression, oligonucleotide-based Affymetrix microarray technology was used to compare the transcriptomes of laser-microdissected stromal cells derived from invasive human breast and prostate carcinoma. Invasive breast and prostate cancer-associated stroma was observed to display distinct transcriptomes, with a limited number of shared genes. Interestingly, both breast and prostate tumor-specific dysregulated stromal genes were observed to cluster breast and prostate cancer patients, respectively, into two distinct groups with statistically different clinical outcomes. By contrast, a gene signature that was common to the reactive stroma of both tumor types did not have survival predictive value. Univariate Cox analysis identified genes whose expression level was most strongly associated with patient survival. Taken together, these observations suggest that the tumor microenvironment displays distinct features according to the tumor type that provides survival-predictive value.

  11. Molecular biology of breast tumors and prognosis [version 1; referees: 3 approved

    Directory of Open Access Journals (Sweden)

    Gustavo Baldassarre

    2016-04-01

    Full Text Available Breast cancer is the most common cancer among women worldwide. Great scientific, economical, and organizational efforts are in place to understand the causes of onset, identify the critical molecular players of progression, and define new lines of intervention providing more benefits and less toxicity. These efforts have certainly not been vain, since overall survival, especially in specific subsets of breast cancer, has greatly improved during the last decades. At present, breast cancer patients’ treatment and care have reached a high standard of quality, and currently one of the most urgent needs resides in the necessity to better distinguish the tumors that need to be more aggressively treated and identify the best therapeutic option tailored to each patient. This objective will be achievable only if the information clarifying the biology of breast cancer can be successfully transferred to the clinic. A common effort by scientists and clinicians toward this integration and toward the use of multidisciplinary approaches will be necessary to reach this important goal.

  12. Resveratrol for breast cancer prevention and therapy: Preclinical evidence and molecular mechanisms.

    Science.gov (United States)

    Sinha, Dona; Sarkar, Nivedita; Biswas, Jaydip; Bishayee, Anupam

    2016-10-01

    Globally, breast cancer is the most frequently diagnosed cancer among women. The major unresolved problems with metastatic breast cancer is recurrence after receiving objective response to chemotherapy, drug-induced side effects of first line chemotherapy and delayed response to second line of treatment. Unfortunately, very few options are available as third line treatment. It is clear that under such circumstances there is an urgent need for new and effective drugs. Phytochemicals are among the most promising chemopreventive treatment options for the management of cancer. Resveratrol (3,5,4'-trihydroxy-trans-stilbene), a non-flavonoid polyphenol present in several dietary sources, including grapes, berries, soy beans, pomegranate and peanuts, has been shown to possess a wide range of health benefits through its effect on a plethora of molecular targets.The present review encompasses the role of resveratrol and its natural/synthetic analogue in the light of their efficacy against tumor cell proliferation, metastasis, epigenetic alterations and for induction of apoptosis as well as sensitization toward chemotherapeutic drugs in various in vitro and in vivo models of breast cancer. The roles of resveratrol as a phytoestrogen, an aromatase inhibitor and in stem cell therapy as well as adjuvent treatment are also discussed. This review explores the full potential of resveratrol in breast cancer prevention and treatment with current limitations, challenges and future directions of research. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Breast Cancer Patients Have Greatly Benefited from the Progress in Molecular Oncology.

    Directory of Open Access Journals (Sweden)

    Bernd L Groner

    2016-09-01

    Full Text Available Cancer research has become a global enterprise, and the number of researchers, as well as the cost for their activities, has skyrocketed. The budget for the National Cancer Institute of the United States National Institutes of Health alone was US$5.2 billion in 2015. Since most of the research is funded by public money, it is perfectly legitimate to ask if these large expenses are worth it. In this brief commentary, we recapitulate some of the breakthroughs that mark the history of breast cancer research over the past decades and emphasize the resulting benefits for afflicted women. In 1971, only 40% of women diagnosed with breast cancer would live another 10 years. Today, nearly 80% of women reach that significant milestone in most developed countries. This dramatic change has afforded breast cancer patients many productive years and a better quality of life. Progress resulted largely from advances in the understanding of the molecular details of the disease and their translation into innovative, rationally designed therapies. These developments are founded on the revolution in molecular and cellular biology, an entirely new array of methods and technologies, the enthusiasm, optimism, and diligence of scientists and clinicians, and the considerable funding efforts from public and private sources. We were lucky to be able to spend our productive years in a period of scientific upheaval in which methods and concepts were revolutionized and that allowed us to contribute, within the global scientific community, to the progress in basic science and clinical practice.

  14. Breast Cancer Patients Have Greatly Benefited from the Progress in Molecular Oncology.

    Science.gov (United States)

    Groner, Bernd L; Hynes, Nancy E

    2016-09-01

    Cancer research has become a global enterprise, and the number of researchers, as well as the cost for their activities, has skyrocketed. The budget for the National Cancer Institute of the United States National Institutes of Health alone was US$5.2 billion in 2015. Since most of the research is funded by public money, it is perfectly legitimate to ask if these large expenses are worth it. In this brief commentary, we recapitulate some of the breakthroughs that mark the history of breast cancer research over the past decades and emphasize the resulting benefits for afflicted women. In 1971, only 40% of women diagnosed with breast cancer would live another 10 years. Today, nearly 80% of women reach that significant milestone in most developed countries. This dramatic change has afforded breast cancer patients many productive years and a better quality of life. Progress resulted largely from advances in the understanding of the molecular details of the disease and their translation into innovative, rationally designed therapies. These developments are founded on the revolution in molecular and cellular biology, an entirely new array of methods and technologies, the enthusiasm, optimism, and diligence of scientists and clinicians, and the considerable funding efforts from public and private sources. We were lucky to be able to spend our productive years in a period of scientific upheaval in which methods and concepts were revolutionized and that allowed us to contribute, within the global scientific community, to the progress in basic science and clinical practice.

  15. Quantitative diffusion weighted imaging parameters in tumor and peritumoral stroma for prediction of molecular subtypes in breast cancer

    Science.gov (United States)

    He, Ting; Fan, Ming; Zhang, Peng; Li, Hui; Zhang, Juan; Shao, Guoliang; Li, Lihua

    2018-03-01

    Breast cancer can be classified into four molecular subtypes of Luminal A, Luminal B, HER2 and Basal-like, which have significant differences in treatment and survival outcomes. We in this study aim to predict immunohistochemistry (IHC) determined molecular subtypes of breast cancer using image features derived from tumor and peritumoral stroma region based on diffusion weighted imaging (DWI). A dataset of 126 breast cancer patients were collected who underwent preoperative breast MRI with a 3T scanner. The apparent diffusion coefficients (ADCs) were recorded from DWI, and breast image was segmented into regions comprising the tumor and the surrounding stromal. Statistical characteristics in various breast tumor and peritumoral regions were computed, including mean, minimum, maximum, variance, interquartile range, range, skewness, and kurtosis of ADC values. Additionally, the difference of features between each two regions were also calculated. The univariate logistic based classifier was performed for evaluating the performance of the individual features for discriminating subtypes. For multi-class classification, multivariate logistic regression model was trained and validated. The results showed that the tumor boundary and proximal peritumoral stroma region derived features have a higher performance in classification compared to that of the other regions. Furthermore, the prediction model using statistical features, difference features and all the features combined from these regions generated AUC values of 0.774, 0.796 and 0.811, respectively. The results in this study indicate that ADC feature in tumor and peritumoral stromal region would be valuable for estimating the molecular subtype in breast cancer.

  16. Risk Differences Between Prediabetes And Diabetes According To Breast Cancer Molecular Subtypes.

    Science.gov (United States)

    Crispo, A; Augustin, L S A; Grimaldi, M; Nocerino, F; Giudice, A; Cavalcanti, E; Di Bonito, M; Botti, G; De Laurentiis, M; Rinaldo, M; Esposito, E; Riccardi, G; Amore, A; Libra, M; Ciliberto, G; Jenkins, D J A; Montella, M

    2017-05-01

    Hyperglycemia and hyperinsulinemia may play a role in breast carcinogenesis and prediabetes and diabetes have been associated with increased breast cancer (BC) risk. However, whether BC molecular subtypes may modify these associations is less clear. We therefore investigated these associations in all cases and by BC molecular subtypes among women living in Southern Italy. Cases were 557 patients with non-metastatic incident BC and controls were 592 outpatients enrolled during the same period as cases and in the same hospital for skin-related non-malignant conditions. Adjusted multivariate logistic regression models were built to assess the risks of developing BC in the presence of prediabetes or diabetes. The analyses were repeated by strata of BC molecular subtypes: Luminal A, Luminal B, HER2+, and Triple Negative (TN). Prediabetes and diabetes were significantly associated with higher BC incidence after controlling for known risk factors (OR = 1.94, 95% CI 1.32-2.87 and OR = 2.46, 95% CI 1.38-4.37, respectively). Similar results were seen in Luminal A and B while in the TN subtype only prediabetes was associated with BC (OR = 2.43, 95% CI 1.11-5.32). Among HER2+ patients, only diabetes was significantly associated with BC risk (OR = 3.04, 95% CI 1.24-7.47). Furthermore, when postmenopausal HER2+ was split into hormone receptor positive versus negative, the association with diabetes remained significant only in the former (OR = 5.13, 95% CI 1.53-17.22). These results suggest that prediabetes and diabetes are strongly associated with BC incidence and that these metabolic conditions may be more relevant in the presence of breast cancer molecular subtypes with positive hormone receptors. J. Cell. Physiol. 232: 1144-1150, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  17. Preoperative core needle biopsy is accurate in determining molecular subtypes in invasive breast cancer

    International Nuclear Information System (INIS)

    Chen, Xiaosong; Yuan, Ying; Fei, Xiaochun; Jin, Xiaolong; Shen, Kunwei; Sun, Long; Mao, Yan; Zhu, Siji; Wu, Jiayi; Huang, Ou; Li, Yafen; Chen, Weiguo; Wang, Jianhua

    2013-01-01

    Estrogen receptor (ER), progesterone receptor (PgR), HER2, and Ki67 have been increasingly evaluated by core needle biopsy (CNB) and are recommended for classifying breast cancer into molecular subtypes. However, the concordance rate between CNB and open excision biopsy (OEB) has not been well documented. Patients with paired CNB and OEB samples from Oct. 2009 to Feb. 2012 in Ruijin Hospital were included. ER, PgR, HER2, and Ki67 were determined by immunohistochemistry (IHC). Patients with HER2 IHC 2+ were further examined by FISH. Cutoff value for Ki67 high expression was 14%. Molecular subtypes were constructed as follows: Luminal A, Luminal B, Triple Negative, and HER2 positive. There were 298 invasive breast cancer patients analyzed. Concordance rates for ER, PgR, and HER2 were 93.6%, 85.9%, and 96.3%, respectively. Ki67 expression was slightly higher in OEB than in CNB samples (29.3% vs. 26.8%, P = 0.046). Good agreement (κ = 0.658) was demonstrated in evaluating molecular subtypes between CNB and OEB, with a concordance rate of 77.2%. We also used a different Ki67 cutoff value (20%) for determining Luminal A and B subtypes in HR (hormone receptor) +/HER2- diseases and the overall concordance rate was 79.2%. However, using a cut-point of Ki67 either 14% or 20% for both specimens, there will be about 14% of HR+/HER2- specimens that are called Luminal A on CNB and Luminal B on OEB. CNB was accurate in determining ER, PgR, and HER2 status as well as non-Luminal molecular subtypes in invasive breast cancer. Ki67 should be retested on OEB samples in HR+/HER2- patients to accurately distinguish Luminal A from B tumors

  18. Acquiring molecular interference functions of X-ray coherent scattering for breast tissues by combination of simulation and experimental methods

    International Nuclear Information System (INIS)

    Chaparian, A.; Oghabian, M. A.; Changizi, V.

    2009-01-01

    Recently, it has been indicated that X-ray coherent scatter from biological tissues can be used to access signature of tissue. Some scientists are interested in studying this effect to get early detection of breast cancer. Since experimental methods for optimization are time consuming and expensive, some scientists suggest using simulation. Monte Carlo codes are the best option for radiation simulation: however, one permanent defect with Monte Carlo codes has been the lack of a sufficient physical model for coherent (Rayleigh) scattering, including molecular interference effects. Materials and Methods: It was decided to obtain molecular interference functions of coherent X-ray scattering for normal breast tissues by combination of modeling and experimental methods. A Monte Carlo simulation program was written to simulate the angular distribution of scattered photons for the normal breast tissue samples. Moreover, experimental diffraction patterns of these tissues were measured by means of energy dispersive X-ray diffraction method. The simulation and experimental data were used to obtain a tabulation of molecular interference functions for breast tissues. Results: With this study a tabulation of molecular interference functions for normal breast tissues Was prepared to facilitate the simulation diffraction patterns of the tissues without any experimental. Conclusion: The method may lead to design new systems for early detection of breast cancer.

  19. Improved characterization of molecular phenotypes in breast lesions using 18F-FDG PET image homogeneity

    Science.gov (United States)

    Cao, Kunlin; Bhagalia, Roshni; Sood, Anup; Brogi, Edi; Mellinghoff, Ingo K.; Larson, Steven M.

    2015-03-01

    Positron emission tomography (PET) using uorodeoxyglucose (18F-FDG) is commonly used in the assessment of breast lesions by computing voxel-wise standardized uptake value (SUV) maps. Simple metrics derived from ensemble properties of SUVs within each identified breast lesion are routinely used for disease diagnosis. The maximum SUV within the lesion (SUVmax) is the most popular of these metrics. However these simple metrics are known to be error-prone and are susceptible to image noise. Finding reliable SUV map-based features that correlate to established molecular phenotypes of breast cancer (viz. estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) expression) will enable non-invasive disease management. This study investigated 36 SUV features based on first and second order statistics, local histograms and texture of segmented lesions to predict ER and PR expression in 51 breast cancer patients. True ER and PR expression was obtained via immunohistochemistry (IHC) of tissue samples from each lesion. A supervised learning, adaptive boosting-support vector machine (AdaBoost-SVM), framework was used to select a subset of features to classify breast lesions into distinct phenotypes. Performance of the trained multi-feature classifier was compared against the baseline single-feature SUVmax classifier using receiver operating characteristic (ROC) curves. Results show that texture features encoding local lesion homogeneity extracted from gray-level co-occurrence matrices are the strongest discriminator of lesion ER expression. In particular, classifiers including these features increased prediction accuracy from 0.75 (baseline) to 0.82 and the area under the ROC curve from 0.64 (baseline) to 0.75.

  20. Dedicated bifurcation stents

    Directory of Open Access Journals (Sweden)

    Ajith Ananthakrishna Pillai

    2012-03-01

    Full Text Available Bifurcation percutaneous coronary intervention (PCI is still a difficult call for the interventionist despite advancements in the instrumentation, technical skill and the imaging modalities. With major cardiac events relate to the side-branch (SB compromise, the concept and practice of dedicated bifurcation stents seems exciting. Several designs of such dedicated stents are currently undergoing trials. This novel concept and pristine technology offers new hope notwithstanding the fact that we need to go a long way in widespread acceptance and practice of these gadgets. Some of these designs even though looks enterprising, the mere complex delivering technique and the demanding knowledge of the exact coronary anatomy makes their routine use challenging.

  1. Dedicating Fermilab's Collider

    Energy Technology Data Exchange (ETDEWEB)

    Anon.

    1986-01-15

    It was a bold move to have a fullscale dedication ceremony for the new proton-antiproton Collider at the Fermilab Tevatron on 13 October, two days before the first collisions were seen. However the particles dutifully behaved as required, and over the following weekend the Collider delivered its goods at a total energy of 1600 GeV, significantly boosting the world record for laboratory collisions.

  2. Response monitoring of breast cancer patients receiving neoadjuvant chemotherapy using quantitative ultrasound, texture, and molecular features.

    Directory of Open Access Journals (Sweden)

    Lakshmanan Sannachi

    Full Text Available Pathological response of breast cancer to chemotherapy is a prognostic indicator for long-term disease free and overall survival. Responses of locally advanced breast cancer in the neoadjuvant chemotherapy (NAC settings are often variable, and the prediction of response is imperfect. The purpose of this study was to detect primary tumor responses early after the start of neoadjuvant chemotherapy using quantitative ultrasound (QUS, textural analysis and molecular features in patients with locally advanced breast cancer.The study included ninety six patients treated with neoadjuvant chemotherapy. Breast tumors were scanned with a clinical ultrasound system prior to chemotherapy treatment, during the first, fourth and eighth week of treatment, and prior to surgery. Quantitative ultrasound parameters and scatterer-based features were calculated from ultrasound radio frequency (RF data within tumor regions of interest. Additionally, texture features were extracted from QUS parametric maps. Prior to therapy, all patients underwent a core needle biopsy and histological subtypes and biomarker ER, PR, and HER2 status were determined. Patients were classified into three treatment response groups based on combination of clinical and pathological analyses: complete responders (CR, partial responders (PR, and non-responders (NR. Response classifications from QUS parameters, receptors status and pathological were compared. Discriminant analysis was performed on extracted parameters using a support vector machine classifier to categorize subjects into CR, PR, and NR groups at all scan times.Of the 96 patients, the number of CR, PR and NR patients were 21, 52, and 23, respectively. The best prediction of treatment response was achieved with the combination mean QUS values, texture and molecular features with accuracies of 78%, 86% and 83% at weeks 1, 4, and 8, after treatment respectively. Mean QUS parameters or clinical receptors status alone predicted the

  3. [Sentinel node biopsy after neoadjuvant chemotherapy in breast cancer. Its relation with molecular subtypes].

    Science.gov (United States)

    Ruano, R; Ramos, M; García-Talavera, J R; Ramos, T; Rosero, A S; González-Orus, J M; Sancho, M

    2014-01-01

    To evaluate the influence of the molecular subtype (MS) in the Sentinel Node Biopsy (SNB) technique after neoadjuvant chemotherapy (NAC) in women with locally advanced breast cancer (BC) and a complete axillary response (CR). A prospective study involving 70 patients with BC treated with NAC was carried out. An axillary lymph node dissection was performed in the first 48 patients (validation group: VG), and in case of micro- or macrometastases in the therapeutic application phase (therapy group:TG). Classified according to MS: 14 luminal A; 16 luminal B HER2-, 13 luminal B HER2+, 10HER2+ non-luminal, 17 triple-negative. SNB was carried out in 98.6% of the cases, with only one false negative result in the VG (FN=2%). Molecular subtype did not affect SN detection. Despite the existence of axillary CR, statistically significant differences were found in the proportion of macrometastasis (16.7% vs. 35.7%, p=0.043) on comparing the pre-NAC cN0 and cN+. Breast tumor response to NAC varied among the different MS, this being lowest in luminal A (21.5%) and highest in non-luminal HER2+ group (80%). HER2+ and triple-negative were the groups with the best axillary histological response both when there was prior clinical involvement and when there was not. Molecular subtype is a predictive factor of the degree of tumor response to NAC in breast cancer. However, it does not affect SNB detection and efficiency. SNB can also be used safely in women with prior node involvement as long as a complete clinical and radiological assessment is made of the node response to NAC. Copyright © 2014 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

  4. MOLECULAR DOCKING OF COMPOUNDS FROM Chaetomium Sp. AGAINST HUMAN ESTROGEN RECEPTOR ALPHA IN SEARCHING ANTI BREAST CANCER

    Directory of Open Access Journals (Sweden)

    Maywan Hariono

    2016-05-01

    Full Text Available A study on molecular docking-based virtual screening has been conducted to select virtual hit of compounds, reported its existence in fungal endophytes of Chaetomium sp. as cytotoxic agent of breast cancer. The ligands were docked into Human Estrogen Receptor alpha (HERa as the protein which regulates the breast cancer growth via estradiol-estrogen receptor binding intervention. The results showed that two compounds bearing xanthone and two compounds bearing benzonaphtyridinedione scaffolds were selected as virtual hit ligands for HERa leading to the conclusion that these compounds were good to be developed as anti breast cancer.

  5. Editors note, and Dedication

    Directory of Open Access Journals (Sweden)

    Laura Mugnai

    2011-12-01

    Full Text Available This Supplement to volume 50 of Phytopathologia Mediterranea contains original, peer reviewed research papers, prepared from presentations at the 7th International Workshop on Grapevine Trunk Diseases (IWGTD. This Workshop was held in Santa Cruz, Chile, 17–21 January 2010, and was organized by the International Council on Grapevine Trunk Diseases (ICGTD.  Publication of this Supplement has been financially assisted by the International Society for Plant Pathology (ISPP.This Supplementary Issue of Phytopathologia Mediterranea is dedicated to the memory of Dr Luigi Chiarappa, the founder and inspiration of the ICGTD.  

  6. Diffusion-weighted imaging features of breast tumours and the surrounding stroma reflect intrinsic heterogeneous characteristics of molecular subtypes in breast cancer

    KAUST Repository

    Fan, Ming

    2017-12-16

    Breast cancer heterogeneity is the main obstacle preventing the identification of patients with breast cancer with poor prognoses and treatment responses; however, such heterogeneity has not been well characterized. The purpose of this retrospective study was to reveal heterogeneous patterns in the apparent diffusion coefficient (ADC) signals in tumours and the surrounding stroma to predict molecular subtypes of breast cancer. A dataset of 126 patients with breast cancer, who underwent preoperative diffusion-weighted imaging (DWI) on a 3.0-T image system, was collected. Breast images were segmented into regions comprising the tumour and surrounding stromal shells in which features that reflect heterogeneous ADC signal distribution were extracted. For each region, imaging features were computed, including the mean, minimum, variance, interquartile range (IQR), range, skewness, kurtosis and entropy of ADC values. Univariate and stepwise multivariate logistic regression modelling was performed to identify the magnetic resonance imaging features that optimally discriminate luminal A, luminal B, human epidermal growth factor 2 (HER2)-enriched and basal-like molecular subtypes. The performance of the predictive models was evaluated using the area under the receiver operating characteristic curve (AUC). Univariate logistic regression analysis showed that the skewness in the tumour boundary achieved an AUC of 0.718 for discrimination between luminal A and non-luminal A tumours, whereas the IQR of the ADC value in the tumour boundary had an AUC of 0.703 for classification of the HER2-enriched subtype. Imaging features in the tumour boundary and the proximal peritumoral stroma corresponded to a higher overall prediction performance than those in other regions. A multivariate logistic regression model combining features in all the regions achieved an overall AUC of 0.800 for the classification of the four tumour subtypes. These findings suggest that features in the tumour

  7. Diffusion-weighted imaging features of breast tumours and the surrounding stroma reflect intrinsic heterogeneous characteristics of molecular subtypes in breast cancer

    KAUST Repository

    Fan, Ming; He, Ting; Zhang, Peng; Cheng, Hu; Zhang, Juan; Gao, Xin; Li, Lihua

    2017-01-01

    Breast cancer heterogeneity is the main obstacle preventing the identification of patients with breast cancer with poor prognoses and treatment responses; however, such heterogeneity has not been well characterized. The purpose of this retrospective study was to reveal heterogeneous patterns in the apparent diffusion coefficient (ADC) signals in tumours and the surrounding stroma to predict molecular subtypes of breast cancer. A dataset of 126 patients with breast cancer, who underwent preoperative diffusion-weighted imaging (DWI) on a 3.0-T image system, was collected. Breast images were segmented into regions comprising the tumour and surrounding stromal shells in which features that reflect heterogeneous ADC signal distribution were extracted. For each region, imaging features were computed, including the mean, minimum, variance, interquartile range (IQR), range, skewness, kurtosis and entropy of ADC values. Univariate and stepwise multivariate logistic regression modelling was performed to identify the magnetic resonance imaging features that optimally discriminate luminal A, luminal B, human epidermal growth factor 2 (HER2)-enriched and basal-like molecular subtypes. The performance of the predictive models was evaluated using the area under the receiver operating characteristic curve (AUC). Univariate logistic regression analysis showed that the skewness in the tumour boundary achieved an AUC of 0.718 for discrimination between luminal A and non-luminal A tumours, whereas the IQR of the ADC value in the tumour boundary had an AUC of 0.703 for classification of the HER2-enriched subtype. Imaging features in the tumour boundary and the proximal peritumoral stroma corresponded to a higher overall prediction performance than those in other regions. A multivariate logistic regression model combining features in all the regions achieved an overall AUC of 0.800 for the classification of the four tumour subtypes. These findings suggest that features in the tumour

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

    Directory of Open Access Journals (Sweden)

    de Souza Emanuel M

    2009-03-01

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

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

    International Nuclear Information System (INIS)

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

    2009-01-01

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

  10. Refinement of Triple-Negative Breast Cancer Molecular Subtypes: Implications for Neoadjuvant Chemotherapy Selection.

    Directory of Open Access Journals (Sweden)

    Brian D Lehmann

    Full Text Available Triple-negative breast cancer (TNBC is a heterogeneous disease that can be classified into distinct molecular subtypes by gene expression profiling. Considered a difficult-to-treat cancer, a fraction of TNBC patients benefit significantly from neoadjuvant chemotherapy and have far better overall survival. Outside of BRCA1/2 mutation status, biomarkers do not exist to identify patients most likely to respond to current chemotherapy; and, to date, no FDA-approved targeted therapies are available for TNBC patients. Previously, we developed an approach to identify six molecular subtypes TNBC (TNBCtype, with each subtype displaying unique ontologies and differential response to standard-of-care chemotherapy. Given the complexity of the varying histological landscape of tumor specimens, we used histopathological quantification and laser-capture microdissection to determine that transcripts in the previously described immunomodulatory (IM and mesenchymal stem-like (MSL subtypes were contributed from infiltrating lymphocytes and tumor-associated stromal cells, respectively. Therefore, we refined TNBC molecular subtypes from six (TNBCtype into four (TNBCtype-4 tumor-specific subtypes (BL1, BL2, M and LAR and demonstrate differences in diagnosis age, grade, local and distant disease progression and histopathology. Using five publicly available, neoadjuvant chemotherapy breast cancer gene expression datasets, we retrospectively evaluated chemotherapy response of over 300 TNBC patients from pretreatment biopsies subtyped using either the intrinsic (PAM50 or TNBCtype approaches. Combined analysis of TNBC patients demonstrated that TNBC subtypes significantly differ in response to similar neoadjuvant chemotherapy with 41% of BL1 patients achieving a pathological complete response compared to 18% for BL2 and 29% for LAR with 95% confidence intervals (CIs; [33, 51], [9, 28], [17, 41], respectively. Collectively, we provide pre-clinical data that could inform

  11. Dedicated accelerator and microprobe line

    International Nuclear Information System (INIS)

    Malmqvist, K.G.; Hylten, G.; Hult, M.; Haakansson, K.; Knox, J.M.; Larsson, N.P.O.; Nilsson, C.; Pallon, J.; Schofield, R.; Swietlicki, E.; Tapper, U.A.S.; Yang Changyi

    1993-01-01

    The development of a dedicated facility for nuclear microprobe analysis and the experiences from using it are discussed. The general properties of the present Lund nuclear microprobe will be described and the advantages of using a dedicated accelerator discussed. (orig.)

  12. Uncovering the molecular secrets of inflammatory breast cancer biology: an integrated analysis of three distinct affymetrix gene expression datasets.

    Science.gov (United States)

    Van Laere, Steven J; Ueno, Naoto T; Finetti, Pascal; Vermeulen, Peter; Lucci, Anthony; Robertson, Fredika M; Marsan, Melike; Iwamoto, Takayuki; Krishnamurthy, Savitri; Masuda, Hiroko; van Dam, Peter; Woodward, Wendy A; Viens, Patrice; Cristofanilli, Massimo; Birnbaum, Daniel; Dirix, Luc; Reuben, James M; Bertucci, François

    2013-09-01

    Inflammatory breast cancer (IBC) is a poorly characterized form of breast cancer. So far, the results of expression profiling in IBC are inconclusive due to various reasons including limited sample size. Here, we present the integration of three Affymetrix expression datasets collected through the World IBC Consortium allowing us to interrogate the molecular profile of IBC using the largest series of IBC samples ever reported. Affymetrix profiles (HGU133-series) from 137 patients with IBC and 252 patients with non-IBC (nIBC) were analyzed using unsupervised and supervised techniques. Samples were classified according to the molecular subtypes using the PAM50-algorithm. Regression models were used to delineate IBC-specific and molecular subtype-independent changes in gene expression, pathway, and transcription factor activation. Four robust IBC-sample clusters were identified, associated with the different molecular subtypes (Pmolecular subtype-independent 79-gene signature, which held independent prognostic value in a series of 871 nIBCs. Functional analysis revealed attenuated TGF-β signaling in IBC. We show that IBC is transcriptionally heterogeneous and that all molecular subtypes described in nIBC are detectable in IBC, albeit with a different frequency. The molecular profile of IBC, bearing molecular traits of aggressive breast tumor biology, shows attenuation of TGF-β signaling, potentially explaining the metastatic potential of IBC tumor cells in an unexpected manner. ©2013 AACR.

  13. Distinct distribution and prognostic significance of molecular subtypes of breast cancer in Chinese women: a population-based cohort study

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    Cai Qiuyin

    2011-07-01

    Full Text Available Abstract Background Molecular classification of breast cancer is an important prognostic factor. The distribution of molecular subtypes of breast cancer and their prognostic value has not been well documented in Asians. Methods A total of 2,791 breast cancer patients recruited for a population-based cohort study were evaluated for molecular subtypes of breast cancer by immunohistochemical assays. Data on clinicopathological characteristics were confirmed by centralized pathology review. The average follow-up of the patients was 53.4 months. Overall and disease-free survival by molecular subtypes of breast cancer were evaluated. Results The prevalence of the luminal A, luminal B, human epidermal growth factor receptor 2 (HER2, and triple-negative subtypes were 48.6%, 16.7%, 13.7%, and 12.9%, respectively. The luminal A subtype was more likely to be diagnosed in older women (P = 0.03 and had a stronger correlation with favorable clinicopathological factors (smaller tumor size, lower histologic grade, and earlier TNM stage than the triple-negative or HER2 subtypes. Women with triple-negative breast cancer had a higher frequency of family history of breast cancer than women with other subtypes (P = 0.048. The 5-year overall/disease-free survival percentages for the luminal A, luminal B, HER2, and triple-negative subtypes were 92.9%/88.6%, 88.6%/85.1%, 83.2%/79.1%, and 80.7%/76.0%, respectively. A similar pattern was observed in multivariate analyses. Immunotherapy was associated with improved overall and disease-free survival for luminal A breast cancer, but reduced disease-free survival (HR = 2.21, 95% CI, 1.09-4.48 for the HER2 subtype of breast cancer. Conclusions The triple-negative and HER2 subtypes were associated with poorer outcomes compared with the luminal A subtype among these Chinese women. The HER2 subtype was more prevalent in this Chinese population compared with Western populations, suggesting the importance of standardized HER2

  14. Molecular characterization of apocrine carcinoma of the breast: validation of an apocrine protein signature in a well-defined cohort

    DEFF Research Database (Denmark)

    Celis, J.E.; Cabezon, T.; Moreira, José

    2009-01-01

    Invasive apocrine carcinomas (IACs), as defined by morphological features, correspond to 0.3-4% of all invasive ductal carcinomas (IDC), and despite the fact that they are histologically distinct from other breast lesions there are currently no standard molecular criteria available...... characterize these lesions as well as to dissect some of the steps in the processes underlying breast apocrine metaplasia and development of precancerous apocrine lesions. Establishing these apocrine-specific markers as best practice for the routine pathology evaluation of breast cancer, however, will require......1), in addition to a set of categorizing markers that are consistently expressed (AR, CD24) or not expressed (ERalpha, PgR, Bcl-2, and GATA-3) by apocrine metaplasia in benign breast lesions and apocrine sweat glands. This panel was used to analyze a well-defined cohort consisting of 14 apocrine...

  15. Revisiting the impact of age and molecular subtype on overall survival after radiotherapy in breast cancer patients

    NARCIS (Netherlands)

    Mao, Jian Hua; Diest, Paul J.Van; Perez-Losada, Jesus; Snijders, Antoine M

    2017-01-01

    Adjuvant radiotherapy (RT) in breast cancer (BC) is often used to eradicate remaining tumor cells following surgery with the goal of maximizing local control and increasing overall survival. The current study investigated the impact of age and BC molecular subtype on overall survival after RT using

  16. Are Breast Cancer Molecular Classes Predictive of Survival in Patients with Long Follow-Up?

    Directory of Open Access Journals (Sweden)

    Danae Pracella

    2013-01-01

    Full Text Available In this study we investigate the clinical outcomes of 305 breast cancer (BC patients, aged 55 years or younger, with long follow-up and according to intrinsic subtypes. The cohort included 151 lymph node negative (LN− and 154 lymph node positive (LN+ patients. Luminal A tumors were mainly LN−, well differentiated, and of stage I; among them AR was an indicator of good prognosis. Luminal B and HER2 positive nonluminal cancers showed higher tumor grade and nodal metastases as well as higher proliferation status and stage. Among luminal tumors, those PR positive and vimentin negative showed a longer survival. HER2-positive nonluminal and TN patients showed a poorer outcome, with BC-specific death mostly occurring within 5 and 10 years. Only luminal tumor patients underwent BC death over 10 years. When patients were divided in to LN− and LN+ no differences in survival were observed in the luminal subgroups. LN− patients have good survival even after 20 years of follow-up (about 75%, while for LN+ patients survival at 20 years (around 40% was comparable to HER2-positive nonluminal and TN groups. In conclusion, in our experience ER-positive breast tumors are better divided by classical clinical stage than molecular classification, and they need longer clinical follow-up especially in cases with lymph node involvement.

  17. Molecular genetics analysis of hereditary breast and ovarian cancer patients in India

    Science.gov (United States)

    Soumittra, Nagasamy; Meenakumari, Balaiah; Parija, Tithi; Sridevi, Veluswami; Nancy, Karunakaran N; Swaminathan, Rajaraman; Rajalekshmy, Kamalalayam R; Majhi, Urmila; Rajkumar, Thangarajan

    2009-01-01

    Background Hereditary cancers account for 5–10% of cancers. In this study BRCA1, BRCA2 and CHEK2*(1100delC) were analyzed for mutations in 91 HBOC/HBC/HOC families and early onset breast and early onset ovarian cancer cases. Methods PCR-DHPLC was used for mutation screening followed by DNA sequencing for identification and confirmation of mutations. Kaplan-Meier survival probabilities were computed for five-year survival data on Breast and Ovarian cancer cases separately, and differences were tested using the Log-rank test. Results Fifteen (16%) pathogenic mutations (12 in BRCA1 and 3 in BRCA2), of which six were novel BRCA1 mutations were identified. None of the cases showed CHEK2*1100delC mutation. Many reported polymorphisms in the exonic and intronic regions of BRCA1 and BRCA2 were also seen. The mutation status and the polymorphisms were analyzed for association with the clinico-pathological features like age, stage, grade, histology, disease status, survival (overall and disease free) and with prognostic molecular markers (ER, PR, c-erbB2 and p53). Conclusion The stage of the disease at diagnosis was the only statistically significant (p < 0.0035) prognostic parameter. The mutation frequency and the polymorphisms were similar to reports on other ethnic populations. The lack of association between the clinico-pathological variables, mutation status and the disease status is likely to be due to the small numbers. PMID:19656415

  18. Molecular genetics analysis of hereditary breast and ovarian cancer patients in India

    Directory of Open Access Journals (Sweden)

    Soumittra Nagasamy

    2009-08-01

    Full Text Available Abstract Background Hereditary cancers account for 5–10% of cancers. In this study BRCA1, BRCA2 and CHEK2*(1100delC were analyzed for mutations in 91 HBOC/HBC/HOC families and early onset breast and early onset ovarian cancer cases. Methods PCR-DHPLC was used for mutation screening followed by DNA sequencing for identification and confirmation of mutations. Kaplan-Meier survival probabilities were computed for five-year survival data on Breast and Ovarian cancer cases separately, and differences were tested using the Log-rank test. Results Fifteen (16% pathogenic mutations (12 in BRCA1 and 3 in BRCA2, of which six were novel BRCA1 mutations were identified. None of the cases showed CHEK2*1100delC mutation. Many reported polymorphisms in the exonic and intronic regions of BRCA1 and BRCA2 were also seen. The mutation status and the polymorphisms were analyzed for association with the clinico-pathological features like age, stage, grade, histology, disease status, survival (overall and disease free and with prognostic molecular markers (ER, PR, c-erbB2 and p53. Conclusion The stage of the disease at diagnosis was the only statistically significant (p

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

    Science.gov (United States)

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

    2015-02-01

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

  20. Integrated Bioinformatics, Environmental Epidemiologic and Genomic Approaches to Identify Environmental and Molecular Links between Endometriosis and Breast Cancer

    Directory of Open Access Journals (Sweden)

    Deodutta Roy

    2015-10-01

    Full Text Available We present a combined environmental epidemiologic, genomic, and bioinformatics approach to identify: exposure of environmental chemicals with estrogenic activity; epidemiologic association between endocrine disrupting chemical (EDC and health effects, such as, breast cancer or endometriosis; and gene-EDC interactions and disease associations. Human exposure measurement and modeling confirmed estrogenic activity of three selected class of environmental chemicals, polychlorinated biphenyls (PCBs, bisphenols (BPs, and phthalates. Meta-analysis showed that PCBs exposure, not Bisphenol A (BPA and phthalates, increased the summary odds ratio for breast cancer and endometriosis. Bioinformatics analysis of gene-EDC interactions and disease associations identified several hundred genes that were altered by exposure to PCBs, phthalate or BPA. EDCs-modified genes in breast neoplasms and endometriosis are part of steroid hormone signaling and inflammation pathways. All three EDCs–PCB 153, phthalates, and BPA influenced five common genes—CYP19A1, EGFR, ESR2, FOS, and IGF1—in breast cancer as well as in endometriosis. These genes are environmentally and estrogen responsive, altered in human breast and uterine tumors and endometriosis lesions, and part of Mitogen Activated Protein Kinase (MAPK signaling pathways in cancer. Our findings suggest that breast cancer and endometriosis share some common environmental and molecular risk factors.

  1. A molecular analysis by gene expression profiling reveals Bik/NBK overexpression in sporadic breast tumor samples of Mexican females

    International Nuclear Information System (INIS)

    García, Normand; Salamanca, Fabio; Astudillo-de la Vega, Horacio; Curiel-Quesada, Everardo; Alvarado, Isabel; Peñaloza, Rosenda; Arenas, Diego

    2005-01-01

    Breast cancer is one of the most frequent causes of death in Mexican women over 35 years of age. At molecular level, changes in many genetic networks have been reported as associated with this neoplasia. To analyze these changes, we determined gene expression profiles of tumors from Mexican women with breast cancer at different stages and compared these with those of normal breast tissue samples. 32 P-radiolabeled cDNA was synthesized by reverse transcription of mRNA from fresh sporadic breast tumor biopsies, as well as normal breast tissue. cDNA probes were hybridized to microarrays and expression levels registered using a phosphorimager. Expression levels of some genes were validated by real time RT-PCR and immunohistochemical assays. We identified two subgroups of tumors according to their expression profiles, probably related with cancer progression. Ten genes, unexpressed in normal tissue, were turned on in some tumors. We found consistent high expression of Bik gene in 14/15 tumors with predominant cytoplasmic distribution. Recently, the product of the Bik gene has been associated with tumoral reversion in different neoplasic cell lines, and was proposed as therapy to induce apoptosis in cancers, including breast tumors. Even though a relationship among genes, for example those from a particular pathway, can be observed through microarrays, this relationship might not be sufficient to assign a definitive role to Bik in development and progression of the neoplasia. The findings herein reported deserve further investigation

  2. Breast

    International Nuclear Information System (INIS)

    Ribeiro, G.G.

    1985-01-01

    The treatment of malignant disease of the breast arouses more controversy and emotion than that of any other form of malignant disease. Many clinical trials have been carried out and others are still in progress. In addition, research work continues in regard to other aspects of the disease, such as epidemiology, population screening, and endocrine factors; yet little is really known about the true biological nature of carcinoma of the breast. A vast amount of literature has accumulated on the treatment of ''operable'' carcinoma of the breast, but it is not proposed to discuss here the merits or demerits of the various suggested treatments. Instead this chapter will be confined to the practical management of carcinoma of the breast as seen from the point of view of radiotherapist. For this reason greater attention will be paid to the radiotherapy techniques as practised at the Christie Hospital

  3. Mass spectrometry-based serum proteome pattern analysis in molecular diagnostics of early stage breast cancer

    Directory of Open Access Journals (Sweden)

    Stobiecki Maciej

    2009-07-01

    Full Text Available Abstract Background Mass spectrometric analysis of the blood proteome is an emerging method of clinical proteomics. The approach exploiting multi-protein/peptide sets (fingerprints detected by mass spectrometry that reflect overall features of a specimen's proteome, termed proteome pattern analysis, have been already shown in several studies to have applicability in cancer diagnostics. We aimed to identify serum proteome patterns specific for early stage breast cancer patients using MALDI-ToF mass spectrometry. Methods Blood samples were collected before the start of therapy in a group of 92 patients diagnosed at stages I and II of the disease, and in a group of age-matched healthy controls (104 women. Serum specimens were purified and the low-molecular-weight proteome fraction was examined using MALDI-ToF mass spectrometry after removal of albumin and other high-molecular-weight serum proteins. Protein ions registered in a mass range between 2,000 and 10,000 Da were analyzed using a new bioinformatic tool created in our group, which included modeling spectra as a sum of Gaussian bell-shaped curves. Results We have identified features of serum proteome patterns that were significantly different between blood samples of healthy individuals and early stage breast cancer patients. The classifier built of three spectral components that differentiated controls and cancer patients had 83% sensitivity and 85% specificity. Spectral components (i.e., protein ions that were the most frequent in such classifiers had approximate m/z values of 2303, 2866 and 3579 Da (a biomarker built from these three components showed 88% sensitivity and 78% specificity. Of note, we did not find a significant correlation between features of serum proteome patterns and established prognostic or predictive factors like tumor size, nodal involvement, histopathological grade, estrogen and progesterone receptor expression. In addition, we observed a significantly (p = 0

  4. A novel high resolution and high efficiency dual head detector for molecular breast imaging: New results from clinical trials

    Energy Technology Data Exchange (ETDEWEB)

    Garibaldi, F., E-mail: franco.garibaldi@iss.infn.i [ISS and INFN Roma, gr. Sanita, Rome (Italy); Cisbani, E.; Colilli, S.; Cusanno, F.; Fratoni, R.; Giuliani, F.; Gricia, M.; Lucentini, M.; Magliozzi, M.L.; Santavenere, F.; Torrioli, S. [ISS and INFN Roma, gr. Sanita, Rome (Italy); Musico, P. [INFN Genova, Genova (Italy); Argentieri, A. [INFN Bari, Bari (Italy); Cossu, E.; Padovano, F.; Simonetti, G. [ISS and INFN Roma, gr. Sanita, Rome (Italy); Schillaci, O. [University of Tor Vergata, Rome (Italy); Majewski, S. [West Virginia University, Morgantown, West Virginia (United States)

    2010-05-21

    Detecting small breast tumors is a challenging task. Molecular Breast Imaging with radionuclides has a central role to play in this respect. Our group has recently designed and implemented a dual detector setup that allows spot compression and improves significantly the performance of the system. The single head detector has been successfully used for clinical trials with 10 patients in comparison with a commercial high resolution detector. Then the dual head system has been showed to have significant advantages for the detection of small tumors.

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

    National Research Council Canada - National Science Library

    Liu, Jingwen

    2005-01-01

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

  6. Mutant p53 protein in serum could be used as a molecular marker in human breast cancer.

    Science.gov (United States)

    Balogh, G A; Mailo, D A; Corte, M M; Roncoroni, P; Nardi, H; Vincent, E; Martinez, D; Cafasso, M E; Frizza, A; Ponce, G; Vincent, E; Barutta, E; Lizarraga, P; Lizarraga, G; Monti, C; Paolillo, E; Vincent, R; Quatroquio, R; Grimi, C; Maturi, H; Aimale, M; Spinsanti, C; Montero, H; Santiago, J; Shulman, L; Rivadulla, M; Machiavelli, M; Salum, G; Cuevas, M A; Picolini, J; Gentili, A; Gentili, R; Mordoh, J

    2006-04-01

    p53 wild-type is a tumor suppressor gene involved in DNA gene transcription or DNA repair mechanisms. When damage to DNA is unrepairable, p53 induces programmed cell death (apoptosis). The mutant p53 gene is the most frequent molecular alteration in human cancer, including breast cancer. Here, we analyzed the genetic alterations in p53 oncogene expression in 55 patients with breast cancer at different stages and in 8 normal women. We measured by ELISA assay the serum levels of p53 mutant protein and p53 antibodies. Immunohistochemistry and RT-PCR using specific p53 primers as well as mutation detection by DNA sequencing were also evaluated in breast tumor tissue. Serological p53 antibody analysis detected 0/8 (0%), 0/4 (0%) and 9/55 (16.36%) positive cases in normal women, in patients with benign breast disease and in breast carcinoma, respectively. We found positive p53 mutant in the sera of 0/8 (0.0%) normal women, 0/4 (0%) with benign breast disease and 29/55 (52.72%) with breast carcinoma. Immunohistochemistry evaluation was positive in 29/55 (52.73%) with mammary carcinoma and 0/4 (0%) with benign breast disease. A very good correlation between p53 mutant protein detected in serum and p53 accumulation by immunohistochemistry (83.3% positive in both assays) was found in this study. These data suggest that detection of mutated p53 could be a useful serological marker for diagnostic purposes.

  7. Molecular predictors of 3D morphogenesis by breast cancer cell lines in 3D culture.

    Directory of Open Access Journals (Sweden)

    Ju Han

    2010-02-01

    Full Text Available Correlative analysis of molecular markers with phenotypic signatures is the simplest model for hypothesis generation. In this paper, a panel of 24 breast cell lines was grown in 3D culture, their morphology was imaged through phase contrast microscopy, and computational methods were developed to segment and represent each colony at multiple dimensions. Subsequently, subpopulations from these morphological responses were identified through consensus clustering to reveal three clusters of round, grape-like, and stellate phenotypes. In some cases, cell lines with particular pathobiological phenotypes clustered together (e.g., ERBB2 amplified cell lines sharing the same morphometric properties as the grape-like phenotype. Next, associations with molecular features were realized through (i differential analysis within each morphological cluster, and (ii regression analysis across the entire panel of cell lines. In both cases, the dominant genes that are predictive of the morphological signatures were identified. Specifically, PPARgamma has been associated with the invasive stellate morphological phenotype, which corresponds to triple-negative pathobiology. PPARgamma has been validated through two supporting biological assays.

  8. Molecular and protein markers for clinical decision making in breast cancer: today and tomorrow.

    Science.gov (United States)

    Harbeck, Nadia; Sotlar, Karl; Wuerstlein, Rachel; Doisneau-Sixou, Sophie

    2014-04-01

    In early breast cancer (eBC), established clinicopathological factors are not sufficient for clinical decision making particularly regarding adjuvant chemotherapy since substantial over- or undertreatment may occur. Thus, novel protein- and molecular markers have been put forward as decision aids. Since these potential prognosis and/or predictive tests differ substantially regarding their methodology, analytical and clinical validation, this review attempts to summarize the essential facts for clinicians. This review focuses on those markers which are the most advanced so far in their development towards routine clinical application, i.e. two protein markers (i.e. uPA/PAI-1 and IHC4) and six molecular multigene tests (i.e. Mammaprint®, Oncotype DX®, PAM50, Endopredict®, the 97-gene genomic grade, and 76 gene Rotterdam signatures). Next to methodological aspects, we summarized the clinical evidences, in particular the main prospective clinical trials which have already been fully recruited (i.e. MINDACT, TAILORx, WSG PLAN B) or are still ongoing (i.e. RxPONDER/SWOG S1007, WSG-ADAPT). Last but not least, this review points out the key elements for clinicians to select one test among the wide panel of proposed assays, for a specific population of patients in term of level of evidence, analytical and clinical validity as well as cost effectiveness. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. Molecular Predictors of 3D Morphogenesis by Breast Cancer Cell Lines in 3D Culture

    Energy Technology Data Exchange (ETDEWEB)

    Han, Ju; Chang, Hang; Giricz, Orsi; Lee, Genee; Baehner, Frederick; Gray, Joe; Bissell, Mina; Kenny, Paraic; Parvin, Bahram

    2010-02-01

    Correlative analysis of molecular markers with phenotypic signatures is the simplest model for hypothesis generation. In this paper, a panel of 24 breast cell lines was grown in 3D culture, their morphology was imaged through phase contrast microscopy, and computational methods were developed to segment and represent each colony at multiple dimensions. Subsequently, subpopulations from these morphological responses were identified through consensus clustering to reveal three clusters of round, grape-like, and stellate phenotypes. In some cases, cell lines with particular pathobiological phenotypes clustered together (e.g., ERBB2 amplified cell lines sharing the same morphometric properties as the grape-like phenotype). Next, associations with molecular features were realized through (i) differential analysis within each morphological cluster, and (ii) regression analysis across the entire panel of cell lines. In both cases, the dominant genes that are predictive of the morphological signatures were identified. Specifically, PPAR? has been associated with the invasive stellate morphological phenotype, which corresponds to triple-negative pathobiology. PPAR? has been validated through two supporting biological assays.

  10. Molecular profiles of screen detected vs. symptomatic breast cancer and their impact on survival: results from a clinical series

    International Nuclear Information System (INIS)

    Crispo, Anna; Esposito, Emanuela; Amore, Alfonso; Di Bonito, Maurizio; Botti, Gerardo; Montella, Maurizio; Barba, Maddalena; D’Aiuto, Giuseppe; De Laurentiis, Michelino; Grimaldi, Maria; Rinaldo, Massimo; Caolo, Giuseppina; D’Aiuto, Massimiliano; Capasso, Immacolata

    2013-01-01

    Stage shift is widely considered a major determinant of the survival benefit conferred by breast cancer screening. However, factors and mechanisms underlying such a prognostic advantage need further clarification. We sought to compare the molecular characteristics of screen detected vs. symptomatic breast cancers and assess whether differences in tumour biology might translate into survival benefit. In a clinical series of 448 women with operable breast cancer, the Kaplan-Meier method and the log-rank test were used to estimate the likelihood of cancer recurrence and death. The Cox proportional hazard model was used for the multivariate analyses including mode of detection, age at diagnosis, tumour size, and lymph node status. These same models were applied to subgroups defined by molecular subtypes. Screen detected breast cancers tended to show more favourable clinicopathological features and survival outcomes compared to symptomatic cancers. The luminal A subtype was more common in women with mammography detected tumours than in symptomatic patients (68.5 vs. 59.0%, p=0.04). Data analysis across categories of molecular subtypes revealed significantly longer disease free and overall survival for screen detected cancers with a luminal A subtype only (p=0.01 and 0.02, respectively). For women with a luminal A subtype, the independent prognostic role of mode of detection on recurrence was confirmed in Cox proportional hazard models (p=0.03). An independent role of modality of detection on survival was also suggested (p=0.05). Molecular subtypes did not substantially explain the differences in survival outcomes between screened and symptomatic patients. However, our results suggest that molecular profiles might play a role in interpreting such differences at least partially. Further studies are warranted to reinterpret the efficacy of screening programmes in the light of tumour biology

  11. Molecular imaging of neutropilin-1 receptor using photoacoustic spectroscopy in breast tumors

    Science.gov (United States)

    Stantz, Keith M.; Cao, Minsong; Liu, Bo; Miller, Kathy D.; Guo, Lili

    2010-02-01

    Purpose: Our purpose is to develop and test a molecular probe that can detect the expression of neutropilin-1 receptor (NPR-1) in vivo using fluorescence imaging and photoacoustic spectroscopy. Introduction: NPR-1 is expressed on endothelial cells and some breast cancer cells, and binds to vascular endothelial growth factor VEGF165, a growth factor associated with pathological tumor angiogenesis. This receptor is coexpressed with VEGFR2 and shown to enhance the binding of VEGF165; therefore, it has the potential to be used as a marker of angiogenic activity and targeted for therapy. Material and Methods: A peptide specific to NPR-1 receptor was synthesized and conjugated to a NIR fluorochrome (IRDye800CW) and was intravenously injected into mice with breast tumors (MCF7VEGF). Probe kinetics was monitored in vivo via near infrared fluorescence (NIRF) within an optical imager for up to 72 hours within the tumor and compared to other organs (liver, muscle) for binding specificity. A multivariate fitting algorithm was used to spectrally deconvolve the IRDye800CW from endogenous hemoglobin signature (hemoglobin concentration and oxygen saturation). Results: Dynamics of the NIR fluorescence signal within the first hour after injection indicates specific binding compared to muscle, with an average tumor-to-muscle ration of 2.00 (+/- 0.27). Spectral analysis clearly indentified the presence of the NPR-1 probe. Based on calibration data, the average tumor concentration from both NIRF and PCT-S was measured to be ~200-300nM. Conclusion: These preliminary results show the capability of PCT to image an exogenous probe in vivo in addition to its hemoglobin state.

  12. Molecular breast imaging: First results from Italian-National-Institute-of-Health clinical trials

    Energy Technology Data Exchange (ETDEWEB)

    Cusanno, F. [Istituto Superiore di Sanita' and INFN gruppo Sanita, Viale Regina Elena 299, 00161 Rome (Italy)]. E-mail: francesco.cusanno@iss.infn.it; Cisbani, E. [Istituto Superiore di Sanita' and INFN gruppo Sanita, Viale Regina Elena 299, 00161 Rome (Italy); Colilli, S. [Istituto Superiore di Sanita' and INFN gruppo Sanita, Viale Regina Elena 299, 00161 Rome (Italy); Fratoni, R. [Istituto Superiore di Sanita' and INFN gruppo Sanita, Viale Regina Elena 299, 00161 Rome (Italy); Garibaldi, F. [Istituto Superiore di Sanita' and INFN gruppo Sanita, Viale Regina Elena 299, 00161 Rome (Italy); Giuliani, F. [Istituto Superiore di Sanita' and INFN gruppo Sanita, Viale Regina Elena 299, 00161 Rome (Italy); Gricia, M. [Istituto Superiore di Sanita' and INFN gruppo Sanita, Viale Regina Elena 299, 00161 Rome (Italy); Lucentini, M. [Istituto Superiore di Sanita' and INFN gruppo Sanita, Viale Regina Elena 299, 00161 Rome (Italy); Magliozzi, M.L. [Istituto Superiore di Sanita' and INFN gruppo Sanita, Viale Regina Elena 299, 00161 Rome (Italy); Santanvenere, F. [Istituto Superiore di Sanita' and INFN gruppo Sanita, Viale Regina Elena 299, 00161 Rome (Italy); Torrioli, S. [Istituto Superiore di Sanita' and INFN gruppo Sanita, Viale Regina Elena 299, 00161 Rome (Italy); Cinti, M.N. [University La Sapienza, Rome (Italy); Pani, R. [University La Sapienza, Rome (Italy); Pellegrini, R. [University La Sapienza, Rome (Italy); Simonetti, G. [University Tor Vergata, Rome (Italy); Schillaci, O. [University Tor Vergata, Rome (Italy); Del Vecchio, S. [CNR Napoli, Naples (Italy); Salvatore, M. [CNR Napoli, Naples (Italy); Majewski, S. [Jefferson Lab, Newport News (United States); De Vincentis, G. [University La Sapienza, Rome (Italy); Scopinaro, F. [University La Sapienza, Rome (Italy)

    2007-02-01

    Dedicated high resolution detectors are needed for detection of small tumors by molecular imaging with radionuclides. Absorptive collimation are typically used for imaging single photon emitters, but it results in a strong reduction in efficiency. Systems based on electronic collimation offer higher efficiency but they are complex and expensive. In case of scintimammography, dual-head detectors increase sensitivity and cancel out the dependence of the lesion depth. In the system presented here, pixellated scintillator arrays (NaI:Tl) were coupled to arrays of PSPMT's, HPK H8500 Flat Panel. A dual-head detector having field of view of 100x100 mm{sup 2} and 150x200 mm{sup 2} were designed and built. The electronic system allows readout of all the anode pad signals. First clinical trials, performed in the framework of the Scintimammography project of Italian National Institute of Health and University of Tor Vergata in Rome, and University of Naples, are presented.

  13. Development of HER2-targeted nanobodies for molecular optical imaging and therapy of breast cancer

    NARCIS (Netherlands)

    Kijanka, M.M.

    2014-01-01

    Breast cancer is a complex disease and the most prevalent cancer in women worldwide. It has been estimated that 1 in 8 women and 1 in 1,000 men will develop breast cancer. Surgical-, chemical- and radiation based therapies are available to breast cancer patients. Early detection of cancer is crucial

  14. Cathepsin K induces platelet dysfunction and affects cell signaling in breast cancer - molecularly distinct behavior of cathepsin K in breast cancer

    International Nuclear Information System (INIS)

    Andrade, Sheila Siqueira; Gouvea, Iuri Estrada; Silva, Mariana Cristina C.; Castro, Eloísa Dognani; Paula, Cláudia A. A. de; Okamoto, Debora; Oliveira, Lilian; Peres, Giovani Bravin; Ottaiano, Tatiana; Facina, Gil; Nazário, Afonso Celso Pinto; Campos, Antonio Hugo J. F. M.; Paredes-Gamero, Edgar Julian; Juliano, Maria; Silva, Ismael D. C. G. da; Oliva, Maria Luiza V.; Girão, Manoel J. B. C.

    2016-01-01

    Breast cancer comprises clinically and molecularly distinct tumor subgroups that differ in cell histology and biology and show divergent clinical phenotypes that impede phase III trials, such as those utilizing cathepsin K inhibitors. Here we correlate the epithelial-mesenchymal-like transition breast cancer cells and cathepsin K secretion with activation and aggregation of platelets. Cathepsin K is up-regulated in cancer cells that proteolyze extracellular matrix and contributes to invasiveness. Although proteolytically activated receptors (PARs) are activated by proteases, the direct interaction of cysteine cathepsins with PARs is poorly understood. In human platelets, PAR-1 and −4 are highly expressed, but PAR-3 shows low expression and unclear functions. Platelet aggregation was monitored by measuring changes in turbidity. Platelets were immunoblotted with anti-phospho and total p38, Src-Tyr-416, FAK-Tyr-397, and TGFβ monoclonal antibody. Activation was measured in a flow cytometer and calcium mobilization in a confocal microscope. Mammary epithelial cells were prepared from the primary breast cancer samples of 15 women with Luminal-B subtype to produce primary cells. We demonstrate that platelets are aggregated by cathepsin K in a dose-dependent manner, but not by other cysteine cathepsins. PARs-3 and −4 were confirmed as the cathepsin K target by immunodetection and specific antagonists using a fibroblast cell line derived from PARs deficient mice. Moreover, through co-culture experiments, we show that platelets activated by cathepsin K mediated the up-regulation of SHH, PTHrP, OPN, and TGFβ in epithelial-mesenchymal-like cells from patients with Luminal B breast cancer. Cathepsin K induces platelet dysfunction and affects signaling in breast cancer cells. The online version of this article (doi:10.1186/s12885-016-2203-7) contains supplementary material, which is available to authorized users

  15. Tumour-associated endothelial-FAK correlated with molecular sub-type and prognostic factors in invasive breast cancer

    International Nuclear Information System (INIS)

    Alexopoulou, Annika N; Ho-Yen, Colan M; Papalazarou, Vassilis; Elia, George; Jones, J Louise; Hodivala-Dilke, Kairbaan

    2014-01-01

    Breast cancer is a heterogeneous disease that can be classified into one of 4 main molecular sub-types: luminal A, luminal B, Her2 over-expressing and basal-like (BL). These tumour sub-types require different treatments and have different risks of disease progression. BL cancers can be considered a sub-group of Triple negative (TN) cancers since they lack estrogen (ER), progesterone (PR) and Her2 expression. No targeted treatment currently exists for TN/BL cancers. Thus it is important to identify potential therapeutic targets and describe their relationship with established prognostic factors. Focal adhesion kinase (FAK) is upregulated in several human cancers and also plays a functional role in tumour angiogenesis. However, the association between breast cancer sub-types and tumour endothelial-FAK expression is unknown. Using immunofluorescence, we quantified FAK expression in tumour endothelial and tumour cell compartments in 149 invasive breast carcinomas and correlated expression with clinical, pathological and molecular parameters. Low endothelial-FAK expression was independently associated with luminal A tumours at univariate (p < 0.001) and multivariate (p = 0.001) analysis. There was a positive correlation between FAK expression in the vascular and tumour cell compartments (Spearman’s correlation co-efficient = 0.394, p < 0.001). Additionally, endothelial and tumour cell FAK expression were significantly increased in TN tumours (p = 0.043 and p = 0.033 respectively), in tumours with negative ER and PR status, and in high grade tumours at univariate analysis. Our findings establish a relationship between endothelial-FAK expression levels and the molecular sub-type of invasive breast cancer, and suggest that endothelial-FAK expression is potentially more clinically relevant than tumour cell FAK expression in breast cancer

  16. The Prognostic Impact of Molecular Subtypes and Very Young Age on Breast Conserving Surgery in Early Stage Breast Cancer

    Science.gov (United States)

    McGuire, Kandace; Alco, Gul; Nur Pilanci, Kezban; Koksal, Ulkuhan I; Elbüken, Filiz; Erdogan, Zeynep; Agacayak, Filiz; Ilgun, Serkan; Sarsenov, Dauren; Öztürk, Alper; İğdem, Şefik; Okkan, Sait; Eralp, Yeşim; Dincer, Maktav; Ozmen, Vahit

    2016-01-01

    Background Premenopausal breast cancer with a triple-negative phenotype (TNBC) has been associated with inferior locoregional recurrence free survival (LRFS) and overall survival (OS) after breast conserving surgery (BCS). The aim of this study is to analyze the association between age, subtype, and surgical treatment on survival in young women (≤40 years) with early breast cancer in a population with a high rate of breast cancer in young women. Methods Three hundred thirty-two patients ≤40 years old with stage I-II invasive breast cancer who underwent surgery at a single institution between 1998 and 2012 were identified retrospectively. Uni- and multivariate analysis evaluated predictors of LRFS, OS, and disease free survival (DFS). Results Most patients (64.2%) underwent BCS. Mean age and follow-up time were 35 (25 ± 3.61) years, and 72 months (range, 24–252), respectively. In multivariate analysis, multicentricity/multifocality and young age (<35 years) independently predicted for poorer DFS and OS. Those aged 35–40 years had higher LRFS and DFS than those <35 in the mastectomy group (p=0.007 and p=0.039, respectively). Patients with TNBC had lower OS compared with patients with luminal A subtype (p=0.042), and those who underwent BCS had higher OS than patients after mastectomy (p=0.015). Conclusion Young age (< 35 years) is an independent predictor of poorer OS and DFS as compared with ages 35–40, even in countries with a lower average age of breast cancer presentation. In addition, TNBC in the young predicts for poorer OS. BCS can be performed in young patients with TNBC, despite their poorer overall survival. PMID:27433412

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

    Directory of Open Access Journals (Sweden)

    MA Hosseinpour Feizi

    2013-12-01

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

  18. The prognostic role of tumor size in early breast cancer in the era of molecular biology.

    Directory of Open Access Journals (Sweden)

    Anaid Anna Kasangian

    Full Text Available The prognosis of early breast cancer (EBC depends on patient and tumor characteristics. The association between tumor size, the largest diameter in TNM staging, and prognosis is well recognized. According to TNM, tumors classified as T2, could have very different volumes; e.g. a tumor of 2.1 cm has a volume of 4500 mm3, while a tumor of 4.9 cm has a volume of 60.000 mm3 even belonging to the same class. The aim of the study is to establish if the prognostic role of tumor size, expressed as diameter and volume, has been overshadowed by other factors.The primary objective is to evaluate the association between tumor dimensions and overall survival (OS / disease free survival (DFS, in our institution from January 1st 2005 to September 30th 2013 in a surgical T1-T2 population. Volume was evaluated with the measurement of three half-diameters of the tumor (a, b and c, and calculated using the following formula: 4/3π x a x b x c.341 patients with T1-T2 EBC were included. 86.5% were treated with conservative surgery. 85.1% had a Luminal subtype, 9.1% were Triple negative and 7.4% were HER2 positive. Median volume was 942 mm3 (range 0.52-31.651.2. 44 patients (12.9% relapsed and 23 patients died. With a median follow-up of 6.5 years, the univariate analysis for DFS showed an association between age, tumor size, volume, histological grading and molecular subtype. The multivariate analysis confirmed the statistically significant association only for molecular subtype (p 0.005, with a worse prognosis for Triple negative and HER2 positive subtypes compared with Luminal (HR: 2.65; 95%CI: 1.34-5.22. Likewise for OS, an association was shown by the multivariate analysis solely for molecular subtype (HER2 and Triple negative vs. Luminal. HR: 2.83; 95% CI:1.46-5.49; p 0.002.In our study, the only parameter that strongly influences survival is molecular subtype. These findings encourage clinicians to choose adjuvant treatment not based on dimensional criteria

  19. Release of low molecular weight silicones and platinum from silicone breast implants.

    Science.gov (United States)

    Lykissa, E D; Kala, S V; Hurley, J B; Lebovitz, R M

    1997-12-01

    We have conducted a series of studies addressing the chemical composition of silicone gels from breast implants as well as the diffusion of low molecular weight silicones (LM-silicones) and heavy metals from intact implants into various surrounding media, namely, lipid-rich medium (soy oil), aqueous tissue culture medium (modified Dulbecco's medium, DMEM), or an emulsion consisting of DMEM plus 10% soy oil. LM-silicones in both implants and surrounding media were detected and quantitated using gas chromatography (GC) coupled with atomic emission (GC-AED) as well as mass spectrometric (GC/MS) detectors, which can detect silicones in the nanogram range. Platinum, a catalyst used in the preparation of silicone gels, was detected and quantitated using inductive argon-coupled plasma/mass spectrometry (ICP-MS), which can detect platinum in the parts per trillion range. Our results indicate that GC-detectable low molecular weight silicones contribute approximately 1-2% to the total gel mass and consist predominantly of cyclic and linear poly-(dimethylsiloxanes) ranging from 3 to 20 siloxane [(CH3)2-Si-O] units (molecular weight 200-1500). Platinum can be detected in implant gels at levels of approximately 700 micrograms/kg by ICP-MS. The major component of implant gels appears to be high molecular weight silicone polymers (HM-silicones) too large to be detected by GC. However, these HM-silicones can be converted almost quantitatively (80% by mass) to LM-silicones by heating implant gels at 150-180 degrees C for several hours. We also studied the rates at which LM-silicones and platinum leak through the intact implant outer shell into the surrounding media under a variety of conditions. Leakage of silicones was greatest when the surrounding medium was lipid-rich, and up to 10 mg/day LM-silicones was observed to diffuse into a lipid-rich medium per 250 g of implant at 37 degrees C. This rate of leakage was maintained over a 7-day experimental period. Similarly, platinum was

  20. The prognostic role of tumor size in early breast cancer in the era of molecular biology.

    Science.gov (United States)

    Kasangian, Anaid Anna; Gherardi, Giorgio; Biagioli, Elena; Torri, Valter; Moretti, Anna; Bernardin, Elena; Cordovana, Andrea; Farina, Gabriella; Bramati, Annalisa; Piva, Sheila; Dazzani, Maria Chiara; Paternò, Emanuela; La Verde, Nicla Maria

    2017-01-01

    The prognosis of early breast cancer (EBC) depends on patient and tumor characteristics. The association between tumor size, the largest diameter in TNM staging, and prognosis is well recognized. According to TNM, tumors classified as T2, could have very different volumes; e.g. a tumor of 2.1 cm has a volume of 4500 mm3, while a tumor of 4.9 cm has a volume of 60.000 mm3 even belonging to the same class. The aim of the study is to establish if the prognostic role of tumor size, expressed as diameter and volume, has been overshadowed by other factors. The primary objective is to evaluate the association between tumor dimensions and overall survival (OS) / disease free survival (DFS), in our institution from January 1st 2005 to September 30th 2013 in a surgical T1-T2 population. Volume was evaluated with the measurement of three half-diameters of the tumor (a, b and c), and calculated using the following formula: 4/3π x a x b x c. 341 patients with T1-T2 EBC were included. 86.5% were treated with conservative surgery. 85.1% had a Luminal subtype, 9.1% were Triple negative and 7.4% were HER2 positive. Median volume was 942 mm3 (range 0.52-31.651.2). 44 patients (12.9%) relapsed and 23 patients died. With a median follow-up of 6.5 years, the univariate analysis for DFS showed an association between age, tumor size, volume, histological grading and molecular subtype. The multivariate analysis confirmed the statistically significant association only for molecular subtype (p 0.005), with a worse prognosis for Triple negative and HER2 positive subtypes compared with Luminal (HR: 2.65; 95%CI: 1.34-5.22). Likewise for OS, an association was shown by the multivariate analysis solely for molecular subtype (HER2 and Triple negative vs. Luminal. HR: 2.83; 95% CI:1.46-5.49; p 0.002). In our study, the only parameter that strongly influences survival is molecular subtype. These findings encourage clinicians to choose adjuvant treatment not based on dimensional criteria but on

  1. MRI texture analysis in differentiating luminal A and luminal B breast cancer molecular subtypes - a feasibility study.

    Science.gov (United States)

    Holli-Helenius, Kirsi; Salminen, Annukka; Rinta-Kiikka, Irina; Koskivuo, Ilkka; Brück, Nina; Boström, Pia; Parkkola, Riitta

    2017-12-29

    The aim of this study was to use texture analysis (TA) of breast magnetic resonance (MR) images to assist in differentiating estrogen receptor (ER) positive breast cancer molecular subtypes. Twenty-seven patients with histopathologically proven invasive ductal breast cancer were selected in preliminary study. Tumors were classified into molecular subtypes: luminal A (ER-positive and/or progesterone receptor (PR)-positive, human epidermal growth factor receptor type 2 (HER2) -negative, proliferation marker Ki-67 MaZda. Texture parameters and tumour volumes were correlated with tumour prognostic factors. Textural differences were observed mainly in precontrast images. The two most discriminative texture parameters to differentiate luminal A and luminal B subtypes were sum entropy and sum variance (p = 0.003). The AUCs were 0.828 for sum entropy (p = 0.004), and 0.833 for sum variance (p = 0.003), and 0.878 for the model combining texture features sum entropy, sum variance (p = 0.001). In the LOOCV, the AUC for model combining features sum entropy and sum variance was 0.876. Sum entropy and sum variance showed positive correlation with higher Ki-67 index. Luminal B types were larger in volume and moderate correlation between larger tumour volume and higher Ki-67 index was also observed (r = 0.499, p = 0.008). Texture features which measure randomness, heterogeneity or smoothness and homogeneity may either directly or indirectly reflect underlying growth patterns of breast tumours. TA and volumetric analysis may provide a way to evaluate the biologic aggressiveness of breast tumours and provide aid in decisions regarding therapeutic efficacy.

  2. Dielectric and FT-Raman spectroscopic approach to molecular identification of breast tumor tissues.

    Science.gov (United States)

    Abd El-Hakam, Rasha; Khalil, Safaa; Mahani, Ragab

    2015-01-01

    FT-Raman spectra and dielectric properties of benign and malignant women breast tissues in vitro were investigated. FT-Raman spectra for the malignant tissues showed a remarkably decrease in the lipid/protein ratio. Dielectric properties of women breast tissues measured in the low frequency range (42-10(6)Hz) were interpreted in spite of electrode polarization effect. Experimental results showed a contrast between the dielectric properties of malignant (Grade II) and benign tissues within the frequency range studied. The permittivity of malignant to normal breast tissue was found to be 160:1 while it could be 1.3:1 for fibrocystic breast tissues. These findings could contribute to distinguish between two breast tissues. The differences in spectral features between benign and malignant tissues may lead to breast cancer detection. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. WE-EF-207-06: Dedicated Cone-Beam Breast CT with Laterally-Shifted Detector: Monte Carlo Evaluation of X-Ray Scatter Distribution and Scatter-To-Primary Ratio

    International Nuclear Information System (INIS)

    Shi, L; Vedantham, S; Karellas, A

    2015-01-01

    Purpose: To determine the spatial distribution of x-ray scatter and scatter-to-primary ratio (SPR) in projections during cone-beam breast CT (CBBCT) with laterally-shifted detector that results in coronal (fan-angle) truncation. Methods: We hypothesized that CBBCT with coronal truncation would lower SPR due to reduction in irradiated breast volume, and that the location of maximum x-ray scatter fluence (scatter-peak) in the detector plane can be determined from the ratio of irradiated-to-total breast volume, breast dimensions and system geometry. Monte Carlo simulations (GEANT4) reflecting a prototype CBBCT system were used to record the position-dependent primary and scatter x-ray photon fluence incident on the detector without coronal truncation (full fan-angle, 2f=24-degrees) and with coronal truncation (fan-angle, f+ f=12+2.7-degrees). Semi-ellipsoidal breasts (10/14/18-cm diameter, chest-wall to nipple length: 0.75xdiameter, 2%/14%/100% fibroglandular content) aligned with the axis-of-rotation (AOR) were modeled. Mono-energy photons were simulated and weighted for 2 spectra (49kVp, 1.4-mm Al HVL; 60kVp, 3.76-mm Al HVL). In addition to SPR, the scatter maps were analyzed to identify the location of the scatter-peak. Results: For CBBCT without fan-angle truncation, the scatter-peaks were aligned with the projection of the AOR onto the detector for all breasts. With truncated fan-beam, the scatter-peaks were laterally-shifted from the projection of the AOR along the fan-angle direction by 14/38/70-pixels for 10/14/18-cm diameter breasts. The corresponding theoretical shifts were 14.8/39.7/68-pixels (p=0.47, 2-tailed paired-ratio t-test). Along the cone-angle, the shift in scatter-peaks between truncated and full-fan angle CBBCT were 2/2/4 -pixels for 10/14/18-cm diameter breasts. CBBCT with fan-angle truncation reduced SPR by 14/22/28% for 10/14/18-cm diameter breasts. 60kVp reduced SPR by 21–25% compared to 49kVp. Peak SPR for CBBCT with fan-angle truncation

  4. Triple-negative breast cancer: the importance of molecular and histologic subtyping, and recognition of low-grade variants.

    Science.gov (United States)

    Pareja, Fresia; Geyer, Felipe C; Marchiò, Caterina; Burke, Kathleen A; Weigelt, Britta; Reis-Filho, Jorge S

    2016-01-01

    Triple-negative breast cancers (TNBCs), defined by lack of expression of estrogen receptor, progesterone receptor and HER2, account for 12-17% of breast cancers and are clinically perceived as a discrete breast cancer subgroup. Nonetheless, TNBC has been shown to constitute a vastly heterogeneous disease encompassing a wide spectrum of entities with marked genetic, transcriptional, histological and clinical differences. Although most TNBCs are high-grade tumors, there are well-characterized low-grade TNBCs that have an indolent clinical course, whose natural history, molecular features and optimal therapy vastly differ from those of high-grade TNBCs. Secretory and adenoid cystic carcinomas are two histologic types of TNBCs underpinned by specific fusion genes; these tumors have an indolent clinical behavior and lack all of the cardinal molecular features of high-grade triple-negative disease. Recent studies of rare entities, including lesions once believed to constitute mere benign breast disease (e.g., microglandular adenosis), have resulted in the identification of potential precursors of TNBC and suggested the existence of a family of low-grade triple-negative lesions that, despite having low-grade morphology and indolent clinical behavior, have been shown to harbor the complex genomic landscape of common forms of TNBC, and may progress to high-grade disease. In this review, we describe the heterogeneity of TNBC and focus on the histologic and molecular features of low-grade forms of TNBC. Germane to addressing the challenges posed by the so-called triple-negative disease is the realization that TNBC is merely a descriptive term, and that low-grade types of TNBC may be driven by distinct sets of genetic alterations.

  5. Association of Screening and Treatment With Breast Cancer Mortality by Molecular Subtype in US Women, 2000-2012.

    Science.gov (United States)

    Plevritis, Sylvia K; Munoz, Diego; Kurian, Allison W; Stout, Natasha K; Alagoz, Oguzhan; Near, Aimee M; Lee, Sandra J; van den Broek, Jeroen J; Huang, Xuelin; Schechter, Clyde B; Sprague, Brian L; Song, Juhee; de Koning, Harry J; Trentham-Dietz, Amy; van Ravesteyn, Nicolien T; Gangnon, Ronald; Chandler, Young; Li, Yisheng; Xu, Cong; Ergun, Mehmet Ali; Huang, Hui; Berry, Donald A; Mandelblatt, Jeanne S

    2018-01-09

    Given recent advances in screening mammography and adjuvant therapy (treatment), quantifying their separate and combined effects on US breast cancer mortality reductions by molecular subtype could guide future decisions to reduce disease burden. To evaluate the contributions associated with screening and treatment to breast cancer mortality reductions by molecular subtype based on estrogen-receptor (ER) and human epidermal growth factor receptor 2 (ERBB2, formerly HER2 or HER2/neu). Six Cancer Intervention and Surveillance Network (CISNET) models simulated US breast cancer mortality from 2000 to 2012 using national data on plain-film and digital mammography patterns and performance, dissemination and efficacy of ER/ERBB2-specific treatment, and competing mortality. Multiple US birth cohorts were simulated. Screening mammography and treatment. The models compared age-adjusted, overall, and ER/ERBB2-specific breast cancer mortality rates from 2000 to 2012 for women aged 30 to 79 years relative to the estimated mortality rate in the absence of screening and treatment (baseline rate); mortality reductions were apportioned to screening and treatment. In 2000, the estimated reduction in overall breast cancer mortality rate was 37% (model range, 27%-42%) relative to the estimated baseline rate in 2000 of 64 deaths (model range, 56-73) per 100 000 women: 44% (model range, 35%-60%) of this reduction was associated with screening and 56% (model range, 40%-65%) with treatment. In 2012, the estimated reduction in overall breast cancer mortality rate was 49% (model range, 39%-58%) relative to the estimated baseline rate in 2012 of 63 deaths (model range, 54-73) per 100 000 women: 37% (model range, 26%-51%) of this reduction was associated with screening and 63% (model range, 49%-74%) with treatment. Of the 63% associated with treatment, 31% (model range, 22%-37%) was associated with chemotherapy, 27% (model range, 18%-36%) with hormone therapy, and 4% (model range, 1

  6. The Role of Ovarian Sex Steroids in Metabolic Homeostasis, Obesity, and Postmenopausal Breast Cancer: Molecular Mechanisms and Therapeutic Implications

    Directory of Open Access Journals (Sweden)

    Viroj Boonyaratanakornkit

    2015-01-01

    Full Text Available Obese postmenopausal women have an increased risk of breast cancer and are likely to have a worse prognosis than nonobese postmenopausal women. The cessation of ovarian function after menopause results in withdrawal of ovarian sex steroid hormones, estrogen, and progesterone. Accumulating evidence suggests that the withdrawal of estrogen and progesterone causes homeostasis imbalances, including decreases in insulin sensitivity and leptin secretion and changes in glucose and lipid metabolism, resulting in a total reduction in energy expenditure. Together with a decrease in physical activity and consumption of a high fat diet, these factors significantly contribute to obesity in postmenopausal women. Obesity may contribute to breast cancer development through several mechanisms. Obesity causes localized inflammation, an increase in local estrogen production, and changes in cellular metabolism. In addition, obese women have a higher risk of insulin insensitivity, and an increase in insulin and other growth factor secretion. In this review, we describe our current understanding of the molecular actions of estrogen and progesterone and their contributions to cellular metabolism, obesity, inflammation, and postmenopausal breast cancer. We also discuss how modifications of estrogen and progesterone actions might be used as a therapeutic approach for obesity and postmenopausal breast cancer.

  7. Integrated Development of Serum Molecular Markers for Early Diagnosis of Breast Cancer

    Science.gov (United States)

    2006-09-01

    development of breast cancer screening test. Increasing our understanding of the role of biomarkers in the etiology and progression of breast cancer...granulocyte-colony-stimulating factor in normal pregnancy and preeclampsia . Hypertens Pregnancy 1999;18:95 – 106. 50. Bux J, Hofmann C, Welte K. Serum G-CSF

  8. Dedication

    NARCIS (Netherlands)

    Hoek, van den C.

    1967-01-01

    Joséphine Th. Koster entered her service at the Rijksherbarium as an assistant, April 1930, in the midst of the economic crisis. She was engaged as an, unsalaried collaborator, the then current type of position the Netherlands’ State could offer its scientific offspring. When Prof. Dr. H. J. Lam,

  9. Dedication

    NARCIS (Netherlands)

    NN,

    1948-01-01

    It is not without some pride and much satisfaction that the present volume, fourth planned in the series, second in sequence of publication, is brought to a successful end. Satisfaction I feel through the fact that the scheme and aim of this work is not only understood by the scientific-botanical

  10. Dedication

    NARCIS (Netherlands)

    Holttum, R.E.

    1959-01-01

    CARL FREDRICK ALBERT CHRISTENSEN (1872-1942) was the founder of modern fern taxonomy. To appreciate the scope of his work, it is necessary to understand the confusions of thought on the subject which persisted through the 19th century and were still evident in the summary prepared (by DIELS) for

  11. Dedicated radial ventriculography pigtail catheter

    Energy Technology Data Exchange (ETDEWEB)

    Vidovich, Mladen I., E-mail: miv@uic.edu

    2013-05-15

    A new dedicated cardiac ventriculography catheter was specifically designed for radial and upper arm arterial access approach. Two catheter configurations have been developed to facilitate retrograde crossing of the aortic valve and to conform to various subclavian, ascending aortic and left ventricular anatomies. The “short” dedicated radial ventriculography catheter is suited for horizontal ascending aortas, obese body habitus, short stature and small ventricular cavities. The “long” dedicated radial ventriculography catheter is suited for vertical ascending aortas, thin body habitus, tall stature and larger ventricular cavities. This new design allows for improved performance, faster and simpler insertion in the left ventricle which can reduce procedure time, radiation exposure and propensity for radial artery spasm due to excessive catheter manipulation. Two different catheter configurations allow for optimal catheter selection in a broad range of patient anatomies. The catheter is exceptionally stable during contrast power injection and provides equivalent cavity opacification to traditional femoral ventriculography catheter designs.

  12. Breast cancer molecular subtypes and survival in a hospital-based sample in Puerto Rico

    International Nuclear Information System (INIS)

    Ortiz, Ana Patricia; Frías, Orquidea; Pérez, Javier; Cabanillas, Fernando; Martínez, Lisa; Sánchez, Carola; Capó-Ramos, David E; González-Keelan, Carmen; Mora, Edna; Suárez, Erick

    2013-01-01

    Information on the impact of hormone receptor status subtypes in breast cancer (BC) prognosis is still limited for Hispanics. We aimed to evaluate the association of BC molecular subtypes and other clinical factors with survival in a hospital-based female population of BC cases in Puerto Rico. We analyzed 663 cases of invasive BC diagnosed between 2002 and 2005. Information on HER-2/neu (HER-2) overexpression, estrogen (ER), and progesterone (PR) receptor status and clinical characteristics were retrieved from hospitals cancer registries and record review. Survival probabilities by covariates of interest were described using the Kaplan–Meier estimators. Cox proportional hazards models were employed to assess factors associated with risk of BC death. Overall, 17.3% of BC cases were triple-negative (TN), 61.8% were Luminal-A, 13.3% were Luminal-B, and 7.5% were HER-2 overexpressed. In the multivariate Cox model, among patients with localized stage, women with TN BC had higher risk of death (adjusted hazard ratio [HR]: 2.57, 95% confidence interval [CI]: 1.29–5.12) as compared to those with Luminal-A status, after adjusting for age at diagnosis. In addition, among women with regional/distant stage at diagnosis, those with TN BC (HR: 5.48, 95% CI: 2.63–11.47) and those HER-2+, including HER-2 overexpressed and Luminal-B, (HR: 2.73, 95% CI:1.30–5.75) had a higher mortality. This is the most comprehensive epidemiological study to date on the impact of hormone receptor expression subtypes in BC survival in Puerto Rico. Consistent to results in other populations, the TN subtype and HER-2+ tumors were associated with decreased survival

  13. Evaluation of breast cancer using intravoxel incoherent motion (IVIM) histogram analysis: comparison with malignant status, histological subtype, and molecular prognostic factors.

    Science.gov (United States)

    Cho, Gene Young; Moy, Linda; Kim, Sungheon G; Baete, Steven H; Moccaldi, Melanie; Babb, James S; Sodickson, Daniel K; Sigmund, Eric E

    2016-08-01

    To examine heterogeneous breast cancer through intravoxel incoherent motion (IVIM) histogram analysis. This HIPAA-compliant, IRB-approved retrospective study included 62 patients (age 48.44 ± 11.14 years, 50 malignant lesions and 12 benign) who underwent contrast-enhanced 3 T breast MRI and diffusion-weighted imaging. Apparent diffusion coefficient (ADC) and IVIM biomarkers of tissue diffusivity (Dt), perfusion fraction (fp), and pseudo-diffusivity (Dp) were calculated using voxel-based analysis for the whole lesion volume. Histogram analysis was performed to quantify tumour heterogeneity. Comparisons were made using Mann-Whitney tests between benign/malignant status, histological subtype, and molecular prognostic factor status while Spearman's rank correlation was used to characterize the association between imaging biomarkers and prognostic factor expression. The average values of the ADC and IVIM biomarkers, Dt and fp, showed significant differences between benign and malignant lesions. Additional significant differences were found in the histogram parameters among tumour subtypes and molecular prognostic factor status. IVIM histogram metrics, particularly fp and Dp, showed significant correlation with hormonal factor expression. Advanced diffusion imaging biomarkers show relationships with molecular prognostic factors and breast cancer malignancy. This analysis reveals novel diagnostic metrics that may explain some of the observed variability in treatment response among breast cancer patients. • Novel IVIM biomarkers characterize heterogeneous breast cancer. • Histogram analysis enables quantification of tumour heterogeneity. • IVIM biomarkers show relationships with breast cancer malignancy and molecular prognostic factors.

  14. Imaging breast adipose and fibroglandular tissue molecular signatures by using hybrid MRI-guided near-infrared spectral tomography

    Science.gov (United States)

    Brooksby, Ben; Pogue, Brian W.; Jiang, Shudong; Dehghani, Hamid; Srinivasan, Subhadra; Kogel, Christine; Tosteson, Tor D.; Weaver, John; Poplack, Steven P.; Paulsen, Keith D.

    2006-06-01

    Magnetic resonance (MR)-guided near-infrared spectral tomography was developed and used to image adipose and fibroglandular breast tissue of 11 normal female subjects, recruited under an institutional review board-approved protocol. Images of hemoglobin, oxygen saturation, water fraction, and subcellular scattering were reconstructed and show that fibroglandular fractions of both blood and water are higher than in adipose tissue. Variation in adipose and fibroglandular tissue composition between individuals was not significantly different across the scattered and dense breast categories. Combined MR and near-infrared tomography provides fundamental molecular information about these tissue types with resolution governed by MR T1 images. hemoglobin | magnetic resonance imaging | water | fat | oxygen saturation

  15. Scalable cloud without dedicated storage

    Science.gov (United States)

    Batkovich, D. V.; Kompaniets, M. V.; Zarochentsev, A. K.

    2015-05-01

    We present a prototype of a scalable computing cloud. It is intended to be deployed on the basis of a cluster without the separate dedicated storage. The dedicated storage is replaced by the distributed software storage. In addition, all cluster nodes are used both as computing nodes and as storage nodes. This solution increases utilization of the cluster resources as well as improves fault tolerance and performance of the distributed storage. Another advantage of this solution is high scalability with a relatively low initial and maintenance cost. The solution is built on the basis of the open source components like OpenStack, CEPH, etc.

  16. Prevalence of molecular subtypes and prognosis of invasive breast cancer in north-east of Morocco: retrospective study

    Directory of Open Access Journals (Sweden)

    Bennis Sanae

    2012-08-01

    Full Text Available Abstract Background Breast carcinoma is known as a heterogeneous disease because gene expression analyses identify several subtypes and the molecular profiles are prognostic and predictive for patients. Our aim, in this study, is to estimate the prevalence of breast cancer subtypes and to determine the relationship between clinico-pathological characteristics, overall survival (OS and disease free survival (DFS for patients coming from north-east of Morocco. Methods We reviewed 366 cases of breast cancer diagnosed between January 2007 to June 2010 at the Department of pathology. Age, size tumor, metastatic profile, node involvement profile, OS and DFS were analyzed on 181 patients. These last parameters were estimated by Kaplan-Meier analysis and log-rank test to estimate outcome differences among subgroups. Results The average age was 45 years, our patients were diagnosed late (57% stage III, 17.5% stage IV with a high average tumor size. Luminal A subtype was more prevalent (53.6% associated with favorable clinic-pathological characteristics, followed by luminal B (16.4%, Her2-overexpressing (12.6%, basal-like (12.6% and unclassified subtype (4.9%. Survival analysis showed a significant difference between subtypes. The triple negative tumors were associated with poor prognosis (49% OS, 39% DFS, whereas the luminal A were associated with a better prognosis (88% OS, 59% DFS. The luminal B and the Her2-overexpressing subtypes were associated with an intermediate prognosis (77% and 75% OS, and 41% and 38% DFS respectively. Conclusion This study showed that molecular classification by immunohistochemistry was necessary for therapeutic decision and prognosis of breast carcinoma. The luminal A subtype was associated with favorable biological characteristics and a better prognosis than triple negative tumors that were associated with a poor prognosis and unfavorable clinic-pathological characteristics.

  17. Early metabolic response using FDG PET/CT and molecular phenotypes of breast cancer treated with neoadjuvant chemotherapy

    International Nuclear Information System (INIS)

    Keam, Bhumsuk; Moon, Woo Kyung; Kim, Tae-You; Park, In Ae; Noh, Dong-Young; Chung, June-Key; Bang, Yung-Jue; Im, Seock-Ah; Koh, Youngil; Han, Sae-Won; Oh, Do-Youn; Cho, Nariya; Kim, Jee Hyun; Han, Wonshik; Kang, Keon Wook

    2011-01-01

    This study was aimed 1) to investigate the predictive value of FDG PET/CT (fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography) for histopathologic response and 2) to explore the results of FDG PET/CT by molecular phenotypes of breast cancer patients who received neoadjuvant chemotherapy. Seventy-eight stage II or III breast cancer patients who received neoadjuvant docetaxel/doxorubicin chemotherapy were enrolled in this study. FDG PET/CTs were acquired before chemotherapy and after the first cycle of chemotherapy for evaluating early metabolic response. The mean pre- and post-chemotherapy standard uptake value (SUV) were 7.5 and 3.9, respectively. The early metabolic response provided by FDG PET/CT after one cycle of neoadjuvant chemotherapy was correlated with the histopathologic response after completion of neoadjuvant chemotherapy (P = 0.002). Sensitivity and negative predictive value were 85.7% and 95.1%, respectively. The estrogen receptor negative phenotype had a higher pre-chemotherapy SUV (8.6 vs. 6.4, P = 0.047) and percent change in SUV (48% vs. 30%, P = 0.038). In triple negative breast cancer (TNBC), the pre-chemotherapy SUV was higher than in non-TNBC (9.8 vs. 6.4, P = 0.008). The early metabolic response using FDG PET/CT could have a predictive value for the assessment of histopathologic non-response of stage II/III breast cancer treated with neoadjuvant chemotherapy. Our findings suggest that the initial SUV and the decline in SUV differed based on the molecular phenotype. ClinicalTrials.gov: http://www.clinicaltrials.gov/ct2/show/NCT01396655

  18. Association of primary tumour FDG uptake with clinical, histopathological and molecular characteristics in breast cancer patients scheduled for neoadjuvant chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Koolen, B.B.; Aukema, T.S. [Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Department of Nuclear Medicine, Amsterdam (Netherlands); Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Department of Surgical Oncology, Amsterdam (Netherlands); Vrancken Peeters, M.J.T.F.D.; Rutgers, E.J.T. [Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Department of Surgical Oncology, Amsterdam (Netherlands); Wesseling, J.; Lips, E.H. [Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Department of Pathology and Experimental Therapy, Amsterdam (Netherlands); Vogel, W.V.; Valdes Olmos, R.A. [Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Department of Nuclear Medicine, Amsterdam (Netherlands); Werkhoven, E. van [Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Department of Biometrics, Amsterdam (Netherlands); Gilhuijs, K.G.A. [Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Department of Radiology, Amsterdam (Netherlands); University Medical Centre Utrecht, Department of Radiology, Utrecht (Netherlands); Rodenhuis, S. [Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Department of Medical Oncology, Amsterdam (Netherlands)

    2012-12-15

    The aim of this study was to evaluate the association of primary tumour {sup 18}F-fluorodeoxyglucose (FDG) uptake with clinical, histopathological and molecular characteristics of breast cancer patients scheduled for neoadjuvant chemotherapy. Second, we wished to establish for which patients pretreatment positron emission tomography (PET)/CT could safely be omitted because of low FDG uptake. PET/CT was performed in 214 primary stage II or III breast cancer patients in the prone position with hanging breasts. Tumour FDG uptake was qualitatively evaluated to determine the possibility of response monitoring with PET/CT and was quantitatively assessed using maximum standardized uptake values (SUV{sub max}). FDG uptake was compared with age, TNM stage, histology, hormone and human epidermal growth factor receptor 2 status, grade, Ki-67 and molecular subtype in univariable and multivariable analyses. In 203 tumours (95 %) FDG uptake was considered sufficient for response monitoring. No subgroup of patients with consistently low tumour FDG uptake could be identified. In a univariable analysis, SUV{sub max} was significantly higher in patients with distant metastases at staging examination, non-lobular carcinomas, tumours with negative hormone receptors, triple negative tumours, grade 3 tumours, and in tumours with a high proliferation index (Ki-67 expression). After multiple linear regression analysis, triple negative and grade 3 tumours were significantly associated with a higher SUV{sub max}. Primary tumour FDG uptake in breast cancer patients scheduled for neoadjuvant chemotherapy is significantly higher in tumours with prognostically unfavourable characteristics. Based on tumour characteristics associated with low tumour FDG uptake, this study was unable to identify a subgroup of patients unlikely to benefit from pretreatment PET/CT. (orig.)

  19. Baseline blood immunological profiling differentiates between Her2-breast cancer molecular subtypes: implications for immunomediated mechanisms of treatment response.

    Science.gov (United States)

    Tudoran, Oana; Virtic, Oana; Balacescu, Loredana; Lisencu, Carmen; Fetica, Bogdan; Gherman, Claudia; Balacescu, Ovidiu; Berindan-Neagoe, Ioana

    2015-01-01

    Breast cancer patients' response to treatment is highly dependent on the primary tumor molecular features, with triple-negative breast tumors having the worst prognosis of all subtypes. According to the molecular features, tumors stimulate the microenvironment to induce distinct immune responses, baseline immune activation being associated with higher likelihood of pathologic response. In this study, we investigated the deconvolution of the immunological status of triple-negative tumors in comparison with luminal tumors and the association with patients' clinicopathological characteristics. Gene expression of 84 inflammatory molecules and their receptors were analyzed in 40 peripheral blood samples from patients with Her2- primary breast cancer tumors. We studied the association of triple-negative phenotype with age, clinical stage, tumor size, lymph nodes, and menopausal status. We observed that more patients with estrogen (ER)/progesterone (PR)-negative tumors had grade III, while more patients with ER/PR-positive tumors had grade II tumors. Gene expression analysis revealed a panel of 14 genes to have differential expression between the two groups: several interleukins: IL13, IL16, IL17C and IL17F, IL1A, IL3; interleukin receptors: IL10RB, IL5RA; chemokines: CXCL13 and CCL26; and cytokines: CSF2, IFNA2, OSM, TNSF13. The expression levels of these genes have been previously shown to be associated with reduced immunological status; indeed, the triple-negative breast cancer patients presented with lower counts of lymphocytes and eosinophils than the ER/PR-positive ones. These results contribute to a better understanding of the possible role of antitumor immune responses in mediating the clinical outcome.

  20. Protein expression profile and prevalence pattern of the molecular classes of breast cancer - a Saudi population based study

    International Nuclear Information System (INIS)

    Al Tamimi, Dalal M; Shawarby, Mohamed A; Ahmed, Ayesha; Hassan, Ammar K; AlOdaini, Amal A

    2010-01-01

    Breast cancer is not a single entity but a diverse group of entities. Advances in gene expression profiling and immunohistochemistry as its surrogate marker have led to the unmasking of new breast cancer molecular subtypes, resulting in the emergence of more elaborate classification systems that are therapeutically and prognostically more predictive. Molecular class distribution across various ethnic groups may also reveal variations that can lead to different clinical outcomes in different populations. We aimed to analyze the spectrum of molecular subtypes present in the Saudi population. ER, PR, HER2, EGFR and CK5/6 were used as surrogate markers for gene expression profiling to classify 231 breast cancer specimens. Correlation of each molecular class with Ki-67 proliferation index, p53 mutation status, histologic type and grade of the tumor was also carried out. Out of 231 cases 9 (3.9%) were classified as luminal A (strong ER +ve, PR +ve or -ve), 37 (16%) as luminal B (weak to moderate ER +ve, and/or PR +ve), 40 (17.3%) as HER2+ (strong or moderately positive HER 2 with confirmation by silver enhanced in-situ hybridization) and 23 (10%) as basal (CK5/6 or EGFR +ve). Co-positivity of different markers in varied patterns was seen in 23 (10%) of cases which were grouped into a hybrid category comprising luminal B-HER2, HER2-basal and luminal-basal hybrids. Ninety nine (42.8%) of the tumors were negative for all five immunohistochemical markers and were labelled as unclassified (penta negative). A high Ki-67 proliferation index was seen in basal (p = 0.007) followed by HER2+ class. Overexpression of p53 was predominantly seen in HER2 + (p = 0.001) followed by the basal group of tumors. A strong correlation was noted between invasive lobular carcinoma and hormone receptor expression with 8 out of 9 lobular carcinoma cases (88.9%) classifiable as luminal cancers. Otherwise, there was no association between the molecular class and the histologic type or grade of the

  1. 15-prostaglandin dehydrogenase expression alone or in combination with ACSM1 defines a subgroup of the apocrine molecular subtype of breast carcinoma

    DEFF Research Database (Denmark)

    Celis, J.E.; Gromov, P.; Cabezon, T.

    2008-01-01

    , papillary, medullary, metaplastic, and apocrine breast carcinomas. Molecular profiling technologies, on the other hand, subdivide breast tumors into five subtypes, basal-like, luminal A, luminal B, normal breast tissue-like, and ERBB2-positive, that have different prognostic characteristics. An additional......Established histopathological criteria divide invasive breast carcinomas into defined groups. Ductal of no specific type and lobular are the two major subtypes accounting for around 75 and 15% of all cases, respectively. The remaining 10% include rarer types such as tubular, cribriform, mucinous...... subclass termed "molecular apocrine" has recently been described, but these lesions did not exhibit all the histopathological features of classical invasive apocrine carcinomas (IACs). IACs make up 0.5-3% of the invasive ductal carcinomas, and despite the fact that they are morphologically distinct from...

  2. Molecular characterization of breast cancer in young Brazilian women Caracterização Molecular do câncer de mama e mulheres brasileiras jovens

    Directory of Open Access Journals (Sweden)

    Leda Viegas de Carvalho

    2010-01-01

    Full Text Available OBJECTIVE: To evaluate the distribution of molecular subtypes of breast tumors diagnosed in young Brazilian women and to analyze the frequency of loss of heterozygocity (LOH in BRCA1 among different molecular subtypes of early-onset breast cancer. METHODS: Samples from 72 cases of invasive breast carcinoma diagnosed in women aged between 19 and 40 years were evaluated using an immunohistochemical panel of biomarkers. Three intragenic BRCA1 locus microsatellites, D17S1322, D17S1323, and D17S855, were PCR amplified from matched normal (lymphocyte and tumor DNAs for (LOH analysis. RESULTS: We found 13 cases (18% that had an immunohistochemical profile consistent with being basal-like. Forty cases (55% were luminal A type; 11% (8 cases were luminal B type, 13% (9 cases were HER2-overexpressing tumors and two cases were ER-/HER2- carcinomas lacking basal marker expression. Four of the 16 informative cases at D17S1322, one of the four informative cases at D17S855, and none of the five informative cases at D17S1323 displayed LOH (four basal-like and one Luminal A. Microsatellite instability (MSI at D17S855 and D17S1322 was found in two cases (one a basal-like and one Luminal A. CONCLUSION: In our study, basal-like tumor was the second most frequent molecular type among young Brazilian women and was only observed in women diagnosed under the age of 35 years. There was no significant difference of LOH at BRCA1 locus rates between basal-like breast tumors and not-basal-like breast tumors (p=0.62. LOH in BRCA1 and MSI in these breast cancers were not frequent but may indicate a small group of breast cancers with a specific molecular makeup.OBJETIVO: Avaliar a distribuição dos subtipos moleculares dos tumores de mama diagnosticados em mulheres brasileiras jovens e determinar a frequência de perda de heterozigose (LOH no gene BRCA1 entre os diferentes subtipos moleculares de tumores. MÉTODOS: Setenta e dois casos de carcinoma invasivo de mama

  3. Widespread molecular patterns associated with drug sensitivity in breast cancer cell lines, with implications for human tumors.

    Directory of Open Access Journals (Sweden)

    Chad J Creighton

    Full Text Available BACKGROUND: Recent landmark studies have profiled cancer cell lines for molecular features, along with measuring the corresponding growth inhibitory effects for specific drug compounds. These data present a tool for determining which subsets of human cancer might be more responsive to particular drugs. To this end, the NCI-DREAM-sponsored DREAM7: Drug Sensitivity Prediction Challenge (sub-challenge 1 set out to predict the sensitivities of 18 breast cancer cell lines to 31 previously untested compounds, on the basis of molecular profiling data and a training subset of cell lines. METHODS AND RESULTS: With 47 teams submitting blinded predictions, team Creighton scored third in terms of overall accuracy. Team Creighton's method was simple and straightforward, incorporated multiple expression data types (RNA-seq, gene array, RPPA, and incorporated all profiled features (not only the "best" predictive ones. As an extension of the approach, cell line data, from public datasets of expression profiling coupled with drug sensitivities (Barretina, Garnett, Heiser were used to "predict" the drug sensitivities in human breast tumors (using data from The Cancer Genome Atlas. Drug sensitivity correlations within human breast tumors showed differences by expression-based subtype, with many associations in line with the expected (e.g. Lapatinib sensitivity in HER2-enriched cancers and others inviting further study (e.g. relative resistance to PI3K inhibitors in basal-like cancers. CONCLUSIONS: Molecular patterns associated with drug sensitivity are widespread, with potentially hundreds of genes that could be incorporated into making predictions, as well as offering biological clues as to the mechanisms involved. Applying the cell line patterns to human tumor data may help generate hypotheses on what tumor subsets might be more responsive to therapies, where multiple cell line datasets representing various drugs may be used, in order to assess consistency of

  4. Anticancer potential of phytochemicals against breast cancer: Molecular docking and simulation approach

    Directory of Open Access Journals (Sweden)

    Bilal Ahmed

    2014-12-01

    Full Text Available Breast cancer malignancy is prevailing among the women not only from the developing countries but also from the developed one at the rate of 18% of total population worldwide. One of the main causes of breast cancer is estrogen receptor alpha. Overexpression of estrogen receptor is seen in number of cases of breast cancer. Tamoxifen was used as a reference drug in present study. Almost 80,000 species of plants are used as a source of medicines. Current study was totally based on the screening of phytochemicals to find out the biomolecules having strong bonding actions as compared to tamoxifen. Present study exhibited that 10 molecules (kushenol K, silybin, taxifolin 3-O-acetate, rosemarinic acid, secundifloran, kushenol N, kurarinol, podophyllotoxone, AC1LCW2L, leachianone G have successful and potential binding with the target molecule as compared to tamoxifen. These molecules can be used for the treatment of breast cancer and birth control.

  5. Glycolytic activity in breast cancer using 18F-FDG PET/CT as prognostic predictor: A molecular phenotype approach.

    Science.gov (United States)

    Garcia Vicente, A M; Soriano Castrejón, A; Amo-Salas, M; Lopez Fidalgo, J F; Muñoz Sanchez, M M; Alvarez Cabellos, R; Espinosa Aunion, R; Muñoz Madero, V

    2016-01-01

    To explore the relationship between basal (18)F-FDG uptake in breast tumors and survival in patients with breast cancer (BC) using a molecular phenotype approach. This prospective and multicentre study included 193 women diagnosed with BC. All patients underwent an (18)F-FDG PET/CT prior to treatment. Maximum standardized uptake value (SUVmax) in tumor (T), lymph nodes (N), and the N/T index was obtained in all the cases. Metabolic stage was established. As regards biological prognostic parameters, tumors were classified into molecular sub-types and risk categories. Overall survival (OS) and disease free survival (DFS) were obtained. An analysis was performed on the relationship between semi-quantitative metabolic parameters with molecular phenotypes and risk categories. The effect of molecular sub-type and risk categories in prognosis was analyzed using Kaplan-Meier and univariate and multivariate tests. Statistical differences were found in both SUVT and SUVN, according to the molecular sub-types and risk classifications, with higher semi-quantitative values in more biologically aggressive tumors. No statistical differences were observed with respect to the N/T index. Kaplan-Meier analysis revealed that risk categories were significantly related to DFS and OS. In the multivariate analysis, metabolic stage and risk phenotype showed a significant association with DFS. High-risk phenotype category showed a worst prognosis with respect to the other categories with higher SUVmax in primary tumor and lymph nodes. Copyright © 2015 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

  6. Sarcoglycans in the normal and pathological breast tissue of humans: an immunohistochemical and molecular study.

    Science.gov (United States)

    Arco, Alba; Favaloro, Angelo; Gioffrè, Mara; Santoro, Giuseppe; Speciale, Francesco; Vermiglio, Giovanna; Cutroneo, Giuseppina

    2012-01-01

    The sarcoglycan complex, consisting of α-, β-, γ-, δ- and ε-sarcoglycans, is a multimember transmembrane system providing a mechanosignaling connection from the cytoskeleton to the extracellular matrix. Whereas the expression of α- and γ-sarcoglycan is restricted to striated muscle, other sarcoglycans are widely expressed. Although many studies have investigated sarcoglycans in all muscle types, insufficient data are available on the distribution of the sarcoglycan complex in nonmuscle tissue. On this basis, we used immunohistochemical and RT-PCR techniques to study preliminarily the sarcoglycans in normal glandular breast tissue (which has never been studied in the literature on these proteins) to verify the effective wider distribution of this complex. Moreover, to understand the role of sarcoglycans, we also tested samples obtained from patients affected by fibrocystic mastopathy and breast fibroadenoma. Our data showed, for the first time, that all sarcoglycans are always detectable in all normal samples both in epithelial and myoepithelial cells; in pathological breast tissue, all sarcoglycans appeared severely reduced. These data demonstrated that all sarcoglycans, not only β-, δ-, and ε-sarcoglycans, have a wider distribution, implying a new unknown role for these proteins. Moreover, in breast diseases, sarcoglycans containing cadherin domain homologs could provoke a loss of strong adhesion between epithelial cells, permitting and facilitating the degeneration of these benign breast tumors into malignant tumors. Consequently, sarcoglycans could play an important and intriguing role in many breast diseases and in particular in tumor progression from benign to malignant. Copyright © 2011 S. Karger AG, Basel.

  7. Epstein-Barr virus and breast cancer: Epidemiological and Molecular study on Egyptian and Iraqi women

    International Nuclear Information System (INIS)

    Zekri, A.N.; Mohamed, W.S.; Hafez, M.M.; Hassan, Z.K.; Bahnassy, A.A.; El-Kassem, F.A.; El-Khalidi, S.J.

    2012-01-01

    Background and purpose: The role of Epstein-Barr virus (EBV) in breast carcinogenesis is still controversial. Unraveling this relationship is potentially important for better understanding of breast cancer etiology, early detection and possibly prevention of breast cancer. The aim of the current study is to unravel the association between EBV and primary invasive breast cancer (PIBC) in two different Arab populations (Egyptian and Iraqi women). Patients and Methods: The study was done on paraffin-embedded tissues of 40 Egyptian and 50 Iraqi patients with PIBC in addition to 20 normal breast tissues as controls for each group. Both controls and neoplastic tissues were assessed for the expression of EBV genes and proteins (EBNA-1, LMP-1, and EBER) as well as CD21 marker by immunohistochemistry (IHC), in situ hybridization (ISH) and PCR techniques. Results: Our gold standard for EBV reactivity in breast cancer cases was positivity of both EBNA1 by PCR and EBER by in situ hybridization. EBV was detected in 18/40 (45%) and 14/50 (28%) of Egyptian and Iraqi women; respectively where p = 0.073, compared to 0/20 (0%) of their control groups (p < 0.05). Regarding the association between EBV positivity and tumor grade, there was not any statistical significant difference between EBV presence and tumor grade in both populations

  8. Precursors and preinvasive lesions of the breast: the role of molecular prognostic markers in the diagnostic and therapeutic dilemma

    Directory of Open Access Journals (Sweden)

    Zografos George C

    2007-05-01

    Full Text Available Abstract Precursors and preinvasive lesions of the breast include atypical ductal hyperplasia (ADH, ductal carcinoma in situ (DCIS, and lobular neoplasia (LN. There is a significant debate regarding the classification, diagnosis, prognosis and management of these lesions. This review article describes the current theories regarding the pathogenesis and molecular evolution of these lesions. It reviews the implication of a variety of molecules in the continuum of breast lesions: estrogen receptors (ER-alpha and ER-beta, c-erb-B2 (Her2/neu, p53, Ki-67, bcl-2, E-cadherin, transforming growth factor-beta (TGF-beta, p27 (Kip1, p16 (INK4a, p21 (Waf1, vascular endothelial growth factor (VEGF. With respect to the aforementioned molecules, this article reviews their pathophysiological importance, and puts the stress on whether they confer additional risk for invasive breast cancer or not. This knowledge has the potential to be of importance in the therapeutic decisions presenting in the common clinical practice.

  9. Enrichment and Molecular Analysis of Breast Cancer Disseminated Tumor Cells from Bone Marrow Using Microfiltration.

    Directory of Open Access Journals (Sweden)

    Sreeraj G Pillai

    Full Text Available Molecular characterization of disseminated tumor cells (DTCs in the bone marrow (BM of breast cancer (BC patients has been hindered by their rarity. To enrich for these cells using an antigen-independent methodology, we have evaluated a size-based microfiltration device in combination with several downstream biomarker assays.BM aspirates were collected from healthy volunteers or BC patients. Healthy BM was mixed with a specified number of BC cells to calculate recovery and fold enrichment by microfiltration. Specimens were pre-filtered using a 70 μm mesh sieve and the effluent filtered through CellSieve microfilters. Captured cells were analyzed by immunocytochemistry (ICC, FISH for HER-2/neu gene amplification status, and RNA in situ hybridization (RISH. Cells eluted from the filter were used for RNA isolation and subsequent qRT-PCR analysis for DTC biomarker gene expression.Filtering an average of 14×106 nucleated BM cells yielded approximately 17-21×103 residual BM cells. In the BC cell spiking experiments, an average of 87% (range 84-92% of tumor cells were recovered with approximately 170- to 400-fold enrichment. Captured BC cells from patients co-stained for cytokeratin and EpCAM, but not CD45 by ICC. RNA yields from 4 ml of patient BM after filtration averaged 135ng per 10 million BM cells filtered with an average RNA Integrity Number (RIN of 5.3. DTC-associated gene expression was detected by both qRT-PCR and RISH in filtered spiked or BC patient specimens but, not in control filtered normal BM.We have tested a microfiltration technique for enrichment of BM DTCs. DTC capture efficiency was shown to range from 84.3% to 92.1% with up to 400-fold enrichment using model BC cell lines. In patients, recovered DTCs can be identified and distinguished from normal BM cells using multiple antibody-, DNA-, and RNA-based biomarker assays.

  10. Molecular and immunohistochemical profiling of invasive micropapillary carcinoma of the breast

    Directory of Open Access Journals (Sweden)

    Thomas A

    2014-10-01

    Full Text Available Alexandra Thomas,1 Ryan W Askeland,2 Natalya V Guseva,2 Ramakrishna Sompallae,2,3 Deqin Ma2 1Department of Internal Medicine, 2Department of Pathology, 3Bioinformatics Division, Iowa Institute of Human Genetics, University of Iowa Hospitals and Clinics, Iowa City, IA, USABackground: In this study, molecular and immunohistochemical profiling of invasive micropapillary carcinoma of the breast was used to identify potentially useful markers for targeted therapies with a focus on BRAF V600E mutation.Methods: Formalin-fixed, paraffin-embedded tumor blocks from seven patients were identified from the archives at our institution and tumor registry from 1997 to 2012. Massively parallel (Next-generation sequencing was performed using the Ion AmpliSeq™ Cancer Hotspot Panel version 2 (Life Technologies, Carlsbad, CA, USA. Mutation analysis for BRAF V600E was performed using a single nucleotide primer extension assay. Immunohistochemistry studies for estrogen receptor (ER, progesterone receptor (PR, Her2/Neu, phosphatase and tensin homolog (PTEN, and non-metastatic protein 23 homologue 1 (NM23H1 were performed using the same tumor blocks. Staining for ER, PR, and Her2/Neu was scored according to American Society of Clinical Oncology/College of American Pathologists guidelines, and a four-tier system, ie, strong homogenous, heterogeneous, positive with negative foci, reduced in more than 50%, and lost in all or majority was used for PTEN and NM23H1 staining.Results: No pathogenic mutations were identified in the tumors by next-generation sequencing. The lack of BRAF V600E mutation was confirmed by single nucleotide primer extension assay. All tumors were positive for ER and PR, and showed no overexpression of Her2/Neu. Loss of or reduced PTEN expression was observed in six of seven cases and was associated with lymph node metastasis. Reduced NM23H1 expression was observed in three of seven cases, all of which had concurrent PTEN loss.Conclusion: No somatic

  11. Efficient dynamic molecular simulation using QSAR model to know inhibition activity in breast cancer medicine

    Science.gov (United States)

    Zharifah, A.; Kusumowardani, E.; Saputro, A.; Sarwinda, D.

    2017-07-01

    According to data from GLOBOCAN (IARC) at 2012, breast cancer was the highest rated of new cancer case by 43.3 % (after controlled by age), with mortality rated as high as 12.9 %. Oncology is a major field which focusing on improving the development of drug and therapeutics cancer in pharmaceutical and biotechnology companies. Nowadays, many researchers lead to computational chemistry and bioinformatic for pharmacophore generation. A pharmacophore describes as a group of atoms in the molecule which is considered to be responsible for a pharmacological action. Prediction of biological function from chemical structure in silico modeling reduces the use of chemical reagents so the risk of environmental pollution decreased. In this research, we proposed QSAR model to analyze the composition of cancer drugs which assumed to be homogenous in character and treatment. Atomic interactions which analyzed are learned through parameters such as log p as descriptors hydrophobic, n_poinas descriptor contour strength and molecular structure, and also various concentrations inhibitor (micromolar and nanomolar) from NCBI drugs bank. The differences inhibitor activity was observed by the presence of IC 50 residues value from inhibitor substances at various concentration. Then, we got a general overview of the state of safety for drug stability seen from its IC 50 value. In our study, we also compared between micromolar and nanomolar inhibitor effect from QSAR model results. The QSAR model analysis shows that the drug concentration with nanomolar is better than micromolar, related with the content of inhibitor substances concentration. This QSAR model got the equation: Log 1/IC50 = (0.284) (±0.195) logP + (0.02) (±0.012) n_poin + (-0.005) (±0.083) Inhibition10.2nanoM + (0.1) (±0.079) Inhibition30.5nanoM + (-0.016) (±0.045) Inhibition91.5nanoM + (-2.572) (±1.570) (n = 13; r = 0.813; r2 = 0.660; s = 0.764; F = 2.720; q2 = 0.660).

  12. Molecular characterization of irinotecan (SN-38) resistant human breast cancer cell lines

    DEFF Research Database (Denmark)

    Jandu, Haatisha; Aluzaite, Kristina; Fogh, Louise

    2016-01-01

    Background: Studies in taxane and/or anthracycline refractory metastatic breast cancer (mBC) patients have shown approximately 30 % response rates to irinotecan. Hence, a significant number of patients will experience irinotecan-induced side effects without obtaining any benefit. The aim of this ......Background: Studies in taxane and/or anthracycline refractory metastatic breast cancer (mBC) patients have shown approximately 30 % response rates to irinotecan. Hence, a significant number of patients will experience irinotecan-induced side effects without obtaining any benefit. The aim...... or an initial high dose of SN-38 (the active metabolite of irinotecan), respectively. The resistant cell lines were analyzed for cross-resistance to other anti-cancer drugs, global gene expression, growth rates, TOP1 and TOP2A gene copy numbers and protein expression, and inhibition of the breast cancer...... of the BCRP in breast cancer patients scheduled for irinotecan treatment. Moreover, LMP400 should be tested in a clinical setting in breast cancer patients with resistance to irinotecan....

  13. СD44+/CD24- markers of cancer stem cells in patients with breast cancer of different molecular subtypes.

    Science.gov (United States)

    Chekhun, S V; Zadvorny, T V; Tymovska, Yu O; Anikusko, M F; Novak, O E; Polishchuk, L Z

    2015-03-01

    To determine frequency of tumors with immunohistochemical markers of cancer stem cells (CSC) CD44+/CD24- in patients with breast cancer (BC) of different molecular subtype and to evaluate their prognostic value. Surgical material of 132 patients with BC stage I-II, age from 23 to 75 years, mean age - 50.2 ± 3.1 years was studied. Clinical, immunohistochemical (expression CD44+/CD24-), morphological, statistical. BC is characterized by heterogeneity of molecular subtypes and expression of markers (CD44+/CD24-). Immunohistochemical study of expression of CSC markers in surgical material has detected their expression in 34 (25.4%) patients with BC of different molecular subtypes. The highest frequency of cells with expression of CSC marker was observed in patients with basal molecular subtype (44.8% patients). Most of BC patients with phenotype CD44+/CD24 had stage I of tumor process (34.3%). Statistical processing of data has showen that Yule colligation coefficient equaled 0.28 (р > 0.05) that argues poor correlation between stage of tumor process and number of tumors with positive expression of CSC markers. Statistical processing of data has showen high correlation between presence of cells with expression of CSC markers and metastases of BC in regional lymph nodes (Yule colligation coefficient equals 0.943; р molecular subtype depending on expression of CSC CD44+/CD24- markers was detected. Survival of patients with basal BC was reliably higher at lack in tumors of cells with CSC markers CD44+/CD24- and, correspondingly, lower at presence of such cells (р markers was not determined (р > 0.05). Significance of tumor cells with markers CD44+/CD24- within the limits of molecular subtype of BC may be additional criterion for advanced biological characteristic of BC, and in patients with BC of basal molecular subtype - for predictive evaluation of individual potential of tumor to aggressive clinical course.

  14. Oral Administration and Detection of a Near-Infrared Molecular Imaging Agent in an Orthotopic Mouse Model for Breast Cancer Screening.

    Science.gov (United States)

    Bhatnagar, Sumit; Verma, Kirti Dhingra; Hu, Yongjun; Khera, Eshita; Priluck, Aaron; Smith, David E; Thurber, Greg M

    2018-05-07

    Molecular imaging is advantageous for screening diseases such as breast cancer by providing precise spatial information on disease-associated biomarkers, something neither blood tests nor anatomical imaging can achieve. However, the high cost and risks of ionizing radiation for several molecular imaging modalities have prevented a feasible and scalable approach for screening. Clinical studies have demonstrated the ability to detect breast tumors using nonspecific probes such as indocyanine green, but the lack of molecular information and required intravenous contrast agent does not provide a significant benefit over current noninvasive imaging techniques. Here we demonstrate that negatively charged sulfate groups, commonly used to improve solubility of near-infrared fluorophores, enable sufficient oral absorption and targeting of fluorescent molecular imaging agents for completely noninvasive detection of diseased tissue such as breast cancer. These functional groups improve the pharmacokinetic properties of affinity ligands to achieve targeting efficiencies compatible with clinical imaging devices using safe, nonionizing radiation (near-infrared light). Together, this enables development of a "disease screening pill" capable of oral absorption and systemic availability, target binding, background clearance, and imaging at clinically relevant depths for breast cancer screening. This approach should be adaptable to other molecular targets and diseases for use as a new class of screening agents.

  15. Molecular genetics analysis of hereditary breast and ovarian cancer patients in India

    OpenAIRE

    Soumittra, Nagasamy; Meenakumari, Balaiah; Parija, Tithi; Sridevi, Veluswami; Nancy, Karunakaran N; Swaminathan, Rajaraman; Rajalekshmy, Kamalalayam R; Majhi, Urmila; Rajkumar, Thangarajan

    2009-01-01

    Abstract Background Hereditary cancers account for 5–10% of cancers. In this study BRCA1, BRCA2 and CHEK2*(1100delC) were analyzed for mutations in 91 HBOC/HBC/HOC families and early onset breast and early onset ovarian cancer cases. Methods PCR-DHPLC was used for mutation screening followed by DNA sequencing for identification and confirmation of mutations. Kaplan-Meier survival probabilities were computed for five-year survival data on Breast and Ovarian cancer cases separately, and differe...

  16. A Partnership Training Program in Breast Cancer Research Using Molecular Imaging Techniques

    National Research Council Canada - National Science Library

    Wang, Paul C

    2006-01-01

    In the first year of this training grant, five faculty members from different departments at the Howard University were trained in molecular imaging with the faculty at the In Vivo Cellular Molecular...

  17. Validation of the prognostic gene portfolio, ClinicoMolecular Triad Classification, using an independent prospective breast cancer cohort and external patient populations

    Science.gov (United States)

    2014-01-01

    Introduction Using genome-wide expression profiles of a prospective training cohort of breast cancer patients, ClinicoMolecular Triad Classification (CMTC) was recently developed to classify breast cancers into three clinically relevant groups to aid treatment decisions. CMTC was found to be both prognostic and predictive in a large external breast cancer cohort in that study. This study serves to validate the reproducibility of CMTC and its prognostic value using independent patient cohorts. Methods An independent internal cohort (n = 284) and a new external cohort (n = 2,181) were used to validate the association of CMTC between clinicopathological factors, 12 known gene signatures, two molecular subtype classifiers, and 19 oncogenic signalling pathway activities, and to reproduce the abilities of CMTC to predict clinical outcomes of breast cancer. In addition, we also updated the outcome data of the original training cohort (n = 147). Results The original training cohort reached a statistically significant difference (p risk groups. Conclusions Both prospective internal cohorts and the independent external cohorts reproduced the triad classification of CMTC and its prognostic significance. CMTC is an independent prognostic predictor, and it outperformed 12 other known prognostic gene signatures, molecular subtype classifications, and all other standard prognostic clinicopathological factors. Our results support further development of CMTC portfolio into a guide for personalized breast cancer treatments. PMID:24996446

  18. Education Level Is a Strong Prognosticator in the Subgroup Aged More Than 50 Years Regardless of the Molecular Subtype of Breast Cancer: A Study Based on the Nationwide Korean Breast Cancer Registry Database.

    Science.gov (United States)

    Hwang, Ki-Tae; Noh, Woochul; Cho, Se-Heon; Yu, Jonghan; Park, Min Ho; Jeong, Joon; Lee, Hyouk Jin; Kim, Jongjin; Oh, Sohee; Kim, Young A

    2017-10-01

    This study investigated the role of the education level (EL) as a prognostic factor for breast cancer and analyzed the relationship between the EL and various confounding factors. The data for 64,129 primary breast cancer patients from the Korean Breast Cancer Registry were analyzed. The EL was classified into two groups according to the education period; the high EL group (≥ 12 years) and low EL group (EL conferred a superior prognosis compared to a low EL in the subgroup aged > 50 years (hazard ratio, 0.626; 95% confidence interval [CI], 0.577 to 0.678) but not in the subgroup aged ≤ 50 years (hazard ratio, 0.941; 95% CI, 0.865 to 1.024). The EL was a significant independent factor in the subgroup aged > 50 years according to multivariate analyses. The high EL group showed more favorable clinicopathologic features and a higher proportion of patients in this group received lumpectomy, radiation therapy, and endocrine therapy. In the high EL group, a higher proportion of patients received chemotherapy in the subgroups with unfavorable clinicopathologic features. The EL was a significant prognosticator across all molecular subtypes of breast cancer. The EL is a strong independent prognostic factor for breast cancer in the subgroup aged > 50 years regardless of the molecular subtype, but not in the subgroup aged ≤ 50 years. Favorable clinicopathologic features and active treatments can explain the main causality of the superior prognosis in the high EL group.

  19. Effects of core needle biopsy and subsequent neoadjuvant chemotherapy on molecular alterations and outcome in breast cancer

    Directory of Open Access Journals (Sweden)

    Xie L

    2018-02-01

    Full Text Available Lingmin Xie,1 Xiaolei Li,2 Qinchuan Wang,1 Jichun Zhou,1 Jun Shen,1 Lixi Luo,1 Yi Lu,1 Linbo Wang1 1Division of Surgical Oncology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Zhejiang, 2Division of Surgical Oncology, The First People’s Hospital of Wenling, Zhejiang, China Objectives: The aim of our study is to evaluate the effect of core needle biopsy (CNB and subsequent neoadjuvant chemotherapy (NAC on the expression of estrogen receptor (ER, progesterone receptor (PR, human epidermal growth hormone receptor 2 (HER2 and Ki67 in breast cancer, and the associated influencing factors.Materials and methods: In this retrospective cohort study, 143 patients with primary operable breast cancer who received NAC were included. ER, PR, HER2 and Ki67 statuses were compared between pretreatment and posttreatment residual samples. A control group of paired core and excision tumors from 123 patients who did not receive NAC within the same study period was also assessed. Data on patients’ clinicopathologic features were collected to identify associated influencing factors.Results: Ki67 value significantly increased in excision tumors compared with paired core samples in controls without presurgery treatment (P<0.01, which was associated with the pathologic lymph node status and the interaction of PR and HER2 status (P=0.008 and 0.028, respectively. In 143 patients who underwent NAC, a significant decrease was observed in the expression of PR and Ki67 after NAC (P=0.003 and P<0.01, respectively. Further subgroup analysis showed that PR decrease was more obvious in premenopausal patients and Luminal A patients (P=0.006 and 0.002, respectively.Conclusion: Core samples could provide more reliable information on determination of molecular subtype than surgical excisions. Decreases in PR and Ki67 expression following NAC could be used as positive prognostic factors. We recommend repeat testing of these biologic markers following NAC for

  20. Molecular characterization of circulating tumor cells from patients with metastatic breast cancer reflects evolutionary changes in gene expression under the pressure of systemic therapy

    Czech Academy of Sciences Publication Activity Database

    Aaltonen, K. E.; Novosadová, Vendula; Bendahl, P.-O.; Graffman, C.; Larsson, A.-M.; Ryden, L.

    2017-01-01

    Roč. 8, č. 28 (2017), s. 45544-45565 ISSN 1949-2553 Institutional support: RVO:86652036 Keywords : metastatic breast cancer * circulating tumor cells * gene expression Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Genetics and heredity (medical genetics to be 3) Impact factor: 5.168, year: 2016

  1. The molecular portraits of breast tumors are conserved across microarray platforms

    Directory of Open Access Journals (Sweden)

    Perreard Laurent

    2006-04-01

    Full Text Available Abstract Background Validation of a novel gene expression signature in independent data sets is a critical step in the development of a clinically useful test for cancer patient risk-stratification. However, validation is often unconvincing because the size of the test set is typically small. To overcome this problem we used publicly available breast cancer gene expression data sets and a novel approach to data fusion, in order to validate a new breast tumor intrinsic list. Results A 105-tumor training set containing 26 sample pairs was used to derive a new breast tumor intrinsic gene list. This intrinsic list contained 1300 genes and a proliferation signature that was not present in previous breast intrinsic gene sets. We tested this list as a survival predictor on a data set of 311 tumors compiled from three independent microarray studies that were fused into a single data set using Distance Weighted Discrimination. When the new intrinsic gene set was used to hierarchically cluster this combined test set, tumors were grouped into LumA, LumB, Basal-like, HER2+/ER-, and Normal Breast-like tumor subtypes that we demonstrated in previous datasets. These subtypes were associated with significant differences in Relapse-Free and Overall Survival. Multivariate Cox analysis of the combined test set showed that the intrinsic subtype classifications added significant prognostic information that was independent of standard clinical predictors. From the combined test set, we developed an objective and unchanging classifier based upon five intrinsic subtype mean expression profiles (i.e. centroids, which is designed for single sample predictions (SSP. The SSP approach was applied to two additional independent data sets and consistently predicted survival in both systemically treated and untreated patient groups. Conclusion This study validates the "breast tumor intrinsic" subtype classification as an objective means of tumor classification that should be

  2. Molecular subtyping of breast cancer improves identification of both high and low risk patients

    DEFF Research Database (Denmark)

    Rossing, Maria; Østrup, Olga; Majewski, Wiktor W.

    2018-01-01

    classification and final reports were available prior to the multidisciplinary conference. Using a prognostic standard mortality rate index (PSMRi) developed by the Danish Breast Cancer Group (DBCG) 39 patients were assigned with an intermediate risk and among these 16 (41%) were furthermore diagnosed...... by the multi-gene signature assigned with a luminal A tumor and consequently spared adjuvant chemotherapy. There was overall agreement between mRNA derived and IHC hormone receptor status, whereas IHC Ki67 protein proliferative index proved inaccurate, compared to the mRNA derived index. Forty-one patients...... with basal-like (basL) subtypes were screened for predisposing mutations regardless of clinical predisposition. Of those 17% carried pathogenic mutations. Conclusion: Transcriptome based subtyping of breast tumors evidently reduces the need for adjuvant chemotherapy and improves identification of women...

  3. The role of tumor molecular subtypes in formation of personalized approach to the theatment of the breast cancer

    Directory of Open Access Journals (Sweden)

    Bondarenko I.N.

    2016-05-01

    Full Text Available Extreme heterogeneity of breast cancer (BC is considered to be one of the reasons that affects the success of treatment. According to current classifications, there are 4 molecular subtypes (MS. The basis for subtypes division is immunohistochemical testing of tumor cell receptors - estrogen (ER, progesterone (PR, HER2-neu and Ki-67. The doctrine of the tumor MS was the basis for the individualization of therapeutic tactics in patients with breast cancer. It was studied that luminal A subtype is the most common and the most favorable, with hormone therapy being a highly effective treatment method. Luminal B subtype, HER2 - positive and triple negative MS is characterized by a high ag­gressiveness, worse survival rate of patients and better prognostic effect of chemotherapy. The importance of determining the level of Ki-67 for assessment of tumor aggressiveness was revealed. Significant differences in receptor status of the primary tumor and metastases were proven. Data on the impact of changes in receptor status of the tumor prognosis are ambiguous and need further study. The use of targeted agents in the treatment of HER2 + patients can significantly improve treatment outcomes, turning this MS from historically aggressive subgroup to quite favorable.

  4. The application of surgical navigation system using optical molecular imaging technology in orthotopic breast cancer and metastasis studies

    Science.gov (United States)

    Chi, Chongwei; Zhang, Qian; Kou, Deqiang; Ye, Jinzuo; Mao, Yamin; Qiu, Jingdan; Wang, Jiandong; Yang, Xin; Du, Yang; Tian, Jie

    2014-02-01

    Currently, it has been an international focus on intraoperative precise positioning and accurate resection of tumor and metastases. The methods such as X-rays, computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography (PET) have played an important role in preoperative accurate diagnosis. However, most of them are inapplicable for intraoperative surgery. We have proposed a surgical navigation system based on optical molecular imaging technology for intraoperative detection of tumors and metastasis. This system collects images from two CCD cameras for real-time fluorescent and color imaging. For image processing, the template matching algorithm is used for multispectral image fusion. For the application of tumor detection, the mouse breast cancer cell line 4T1-luc, which shows highly metastasis, was used for tumor model establishment and a model of matrix metalloproteinase (MMP) expressing breast cancer. The tumor-bearing nude mice were given tail vein injection of MMP 750FAST (PerkinElmer, Inc. USA) probe and imaged with both bioluminescence and fluorescence to assess in vivo binding of the probe to the tumor and metastases sites. Hematoxylin and eosin (H&E) staining was performed to confirm the presence of tumor and metastasis. As a result, one tumor can be observed visually in vivo. However liver metastasis has been detected under surgical navigation system and all were confirmed by histology. This approach helps surgeons to find orthotopic tumors and metastasis during intraoperative resection and visualize tumor borders for precise positioning. Further investigation is needed for future application in clinics.

  5. Early Diagnosis of Breast Cancer using Molecular, Biochemical and Pathological Markers

    OpenAIRE

    Salah E.D. El-Assal; Adel A. El-Tarras; Samir M. Abd-alla

    2011-01-01

    Problem statement: Laboratory diagnosis of breast cancer in most of the hospitals has traditionally been performed using cell culture and the direct hormone receptor assay, which are money and time consuming. Approach: This study was performed in order to direct the attention toward increasing the efficiency of early diagnosis in clinical laboratories at the western region of KSA and Egypt using recent PCR-dependent protocols i.e., Randomly Amplified Polymorphic DNA (RAPDs) and Reverse Transc...

  6. The Risk and Clinical/Molecular Characteristics of Breast Cancer in Women with Neurofibromatosis Type 1

    Science.gov (United States)

    2016-03-01

    diagnostic criteria for her case. Without the family history , this woman would not fit the diagnostic criteria for NF1. In addition, based on the... woman in this cohort and belong to a total of 16 kinships (Table 1). Family history of NF1 in female relatives was collected based on the pedigree in...cancer and other cancers. A total of 423 cases of NF1 women have been reviewed. History of breast cancer was found in 20. Family history of cancer

  7. Clinical Trials of Precision Medicine through Molecular Profiling: Focus on Breast Cancer.

    Science.gov (United States)

    Zardavas, Dimitrios; Piccart-Gebhart, Martine

    2015-01-01

    High-throughput technologies of molecular profiling in cancer, such as gene-expression profiling and next-generation sequencing, are expanding our knowledge of the molecular landscapes of several cancer types. This increasing knowledge coupled with the development of several molecularly targeted agents hold the promise for personalized cancer medicine to be fully realized. Moreover, an expanding armamentarium of targeted agents has been approved for the treatment of specific molecular cancer subgroups in different diagnoses. According to this paradigm, treatment selection should be dictated by the specific molecular aberrations found in each patient's tumor. The classical clinical trials paradigm of patients' eligibility being based on clinicopathologic parameters is being abandoned, with current clinical trials enrolling patients on the basis of specific molecular aberrations. New, innovative trial designs have been generated to better tackle the multiple challenges induced by the increasing molecular fragmentation of cancer, namely: (1) longitudinal cohort studies with or without downstream trials, (2) studies assessing the clinical utility of molecular profiling, (3) master or umbrella trials, (4) basket trials, (5) N-of-1 trials, and (6) adaptive design trials. This article provides an overview of the challenges for clinical trials in the era of molecular profiling of cancer. Subsequently, innovative trial designs with respective examples and their potential to expedite efficient clinical development of targeted anticancer agents is discussed.

  8. A comparative study of the biologic and molecular basis of murine mammary carcinoma: a model for human breast cancer

    International Nuclear Information System (INIS)

    Schlom, J.; Kufe, D.; Hehlman, R.; Spiegelman, S.; Bentvelzen, P.; Michalides, R.; Hageman, P.

    1976-01-01

    Tritiated-DNA complementary to mouse mammary tumor virus (MMTV) RNA was synthesized in an endogeneous reaction with MMTV particles. This DNA was used as a probe via molecular hybridization to detect MMTV-specific RNA in 'spontaneous' mammary tumors of several strains of mice, including the 'nonproducer' BALB/c mammary tumors. MMTV-specific RNA was also found in certain normal tissues (spleen, kidney, and epididymis) of a high-mammary-cancer strain (GR). Aging or treatment with nonviral carcinogens also induced the appearance of MMTV-specific RNA in certain normal tissues of the low-mammary-cancer strains, C57BL and BALB/c. The relationship of the presence of MMTV-specific RNA to the etiology and pathogenesis of murine mammary neoplasia and its potential application to human breast cancer are discussed

  9. Dedicated education unit: student perspectives.

    Science.gov (United States)

    Nishioka, Vicki M; Coe, Michael T; Hanita, Makoto; Moscato, Susan R

    2014-01-01

    The study compared students' perceptions of their clinical learning experiences in a dedicated education unit (DEU) with their experiences in traditional clinical education. Unlike traditional academic-instructor models, expert nurses in the DEU provide clinical education to students with faculty support. This repeated measures design used student surveys, supplemented by focus group data. Students were more likely to agree that their clinical learning experience was high quality and they had a consistent mentoring relationship during DEU rotations. Students also reported the quality of the unit's learning environment, the leadership style of the nurse manager, and the nursing care on the unit was more favorable in DEUs than traditional units. Consistent with their changed role in DEUs, faculty members were less active in helping students integrate theory and practice. These findings provide additional evidence of the value that the DEU model contributes to high-quality clinical education.

  10. Phosphoproteomic analysis for the identification of predictive molecular factors and new molecular targets in breast, colorectal, ovary, and lung cancer

    International Nuclear Information System (INIS)

    Belluco, C.; De Paoli, P.

    2009-01-01

    Neoadjuvant chemotherapy is a standard therapeutic approach for several types of locally advanced and metastatic tumors. Molecular factors predictive of response to therapy are highly needed for exploiting the potential benefit of properative chemotherapy. Moreover, neoadjuvant chemotherapy represents an ideal clinical model for studying predictive factors since it allows to obtain pre-treatment tissue biopsies which can be analyzed and the results compared to clinical and pathological response. Protein kinases represent some of the most important drug targets in medicine today and their aberrant activation are involved in many disease processes including cancer development and progression

  11. Clear-PEM, a dedicated PET camera for mammography

    CERN Document Server

    Lecoq, P

    2002-01-01

    Preliminary results suggest that Positron Emission Mammography (PEM) can offer a noninvasive method for the diagnosis of breast cancer. Metabolic images from PEM contain unique information not available from conventional morphologic imaging techniques and aid in expeditiously establishing the diagnosis of cancer. A dedicated machine seems to offer better perspectives in terms of position resolution and sensitivity. This paper describes the concept of Clear-PEM, the system presently developed by the Crystal Clear Collaboration at CERN for an evaluation of this approach. This device is based on new crystals introduced by the Crystal Clear as well as on modern data acquisition techniques developed for the large experiments in high energy physics experiments.

  12. [{sup 18}F]FDG PET/CT features for the molecular characterization of primary breast tumors

    Energy Technology Data Exchange (ETDEWEB)

    Antunovic, Lidija [Humanitas Research Hospital, Nuclear Medicine Department, Milan (Italy); Gallivanone, Francesca; Castiglioni, Isabella [National Research Council, Laboratory of Innovation and Integration in Molecular Medicine, Institute of Molecular Bioimaging and Physiology, Milan (Italy); Sollini, Martina; Kirienko, Margarita [Humanitas University, Department of Biomedical Sciences, Milan (Italy); Sagona, Andrea; Tinterri, Corrado [Humanitas Research Hospital, Breast Unit, Milan (Italy); Invento, Alessandra [Integrated University Hospital, Breast Unit, Verona (Italy); Manfrinato, Giulia [University of Milan, Residency Program in Nuclear Medicine, Milan (Italy); Chiti, Arturo [Humanitas Research Hospital, Nuclear Medicine Department, Milan (Italy); Humanitas University, Department of Biomedical Sciences, Milan (Italy)

    2017-11-15

    The aim of this study was to evaluate the role of imaging features derived from [{sup 18}F]FDG-PET/CT to provide in vivo characterization of breast cancer (BC). Images from 43 patients with a first diagnosis of BC were reviewed. Images were acquired before any treatment. Histological data were derived from pretreatment biopsy or surgical histological specimen; these included tumor type, grade, ER and PgR receptor status, lymphovascular invasion, Ki67 index, HER2 status, and molecular subtype. Standard parameters (SUV{sub mean}, TLG, MTV) and advanced imaging features (histogram-based and shape and size features) were evaluated. Univariate analysis, hierarchical clustering analysis, and exact Fisher's test were used for statistical analysis of data. Imaging-derived metrics were reduced evaluating the mutual correlation within group of features as well as the mutual correlation between groups of features to form a signature. A significant correlation was found between some advanced imaging features and the histological type. Different molecular subtypes were characterized by different values of two histogram-based features (median and energy). A significant association was observed between the imaging signature and luminal A and luminal B HER2 negative molecular subtype and also when considering luminal A, luminal B HER2-negative and HER2-positive groups. Similar results were found between the signature and all five molecular subtypes and also when considering the histological types of BC. Our results suggest a complementary role of standard PET imaging parameters and advanced imaging features for the in vivo biological characterization of BC lesions. (orig.)

  13. 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 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.

  14. Hemangiosarcoma after breast-conserving therapy of breast cancer. Report of four cases with molecular genetic diagnosis and literature review; Haemangiosarkom nach brusterhaltender Therapie beim Mammakarzinom. Vier Fallbeispiele mit molekulargenetischer Diagnostik und Literaturuebersicht

    Energy Technology Data Exchange (ETDEWEB)

    Nestle-Kraemling, Carolin [Universitaetsklinikum, Duesseldorf (Germany). Frauenklinik; Boelke, Edwin; Budach, Wilfried [Universitaetsklinikum Duesseldorf (DE). Klinik und Poliklinik fuer Strahlentherapie und radiologische Onkologie] (and others)

    2011-10-15

    Hemangiosarcomas of the breast represent a rare disease of the breast mainly occurring as secondary neoplasias with a latency of 5-10 years after primary treatment of breast cancer and are associated with an unfavourable prognosis. Radiation therapy, which is integrated within the concept of breast conserving therapy ranks as the main risk factor. In this report we describe the clinical course of 4 patients including their molecular genetic pattern and give a summary of the actual literature. Hemangiosarcomas occur as a secondary neoplasm with a latency of 5-10 years after primary treatment of breast cancer and have an unfavorable prognosis. A genetic predisposition is assumed, but we could not find a significant role of tumor suppressor genes BRCA1, BRCA2 or p53 in our patients. Due to limited data available for these tumors, recommendations for therapy include radical tumor resection achieving wide free margins and inconsistent regimens of chemo- and/or immunetherapy modalities. In the majority these are based on systemic therapy regimens for other cutaneous sarcomas, such as Kaposi's sarcoma. Efforts should be taken for a nation-wide systematic registration of all cases of post-irradiation hemangiosarcomas.

  15. Molecular MR Imaging of CD44 in Breast Cancer with Hyaluronan-Based Contrast Agents

    Science.gov (United States)

    2009-09-01

    linear polysaccharide composed of alternating (β-1,4)-linked d- glucuronic acid and (β-1,3) N-acetyl-d-glucosamine residues with molecular weights as...enzymatic reactions in-vivo that generate polysaccharides of decreasing sizes, which in principle may facilitate the timely excretion of HA based...14CO2) or in urine (as low molecular weight HA or monosaccharide fragments). The same authors also reported that the total amount of excretion into

  16. Inhibitory effects and molecular mechanisms of tetrahydrocurcumin against human breast cancer MCF-7 cells

    Directory of Open Access Journals (Sweden)

    Xiao Han

    2016-02-01

    Full Text Available Background: Tetrahydrocurcumin (THC, an active metabolite of curcumin, has been reported to have similar biological effects to curcumin, but the mechanism of the antitumor activity of THC is still unclear. Methods: The present study was to investigate the antitumor effects and mechanism of THC in human breast cancer MCF-7 cells using the methods of MTT assay, LDH assay, flow cytometry analysis, and western blot assay. Results: THC was found to have markedly cytotoxic effect and antiproliferative activity against MCF-7 cells in a dose-dependent manner with the IC50 for 24 h of 107.8 μM. Flow cytometry analysis revealed that THC mediated the cell-cycle arrest at G0/G1 phase, and 32.8% of MCF-7 cells entered the early phase of apoptosis at 100 μM for 24 h. THC also dose-dependently led to apoptosis in MCF-7 cells via the mitochondrial pathway, as evidenced by the activation of caspase-3 and caspase-9, the elevation of intracellular ROS, a decrease in Bcl-2 and PARP expression, and an increase in Bax expression. Meanwhile, cytochrome C was released to cytosol and the loss of mitochondria membrane potential (Δψm was observed after THC treatment. Conclusion: THC is an excellent source of chemopreventive agents in the treatment of breast cancer and has excellent potential to be explored as antitumor precursor compound.

  17. Unique molecular signatures as a hallmark of patients with metastatic breast cancer: implications for current treatment paradigms.

    Science.gov (United States)

    Wheler, Jennifer J; Parker, Barbara A; Lee, Jack J; Atkins, Johnique T; Janku, Filip; Tsimberidou, Apostolia M; Zinner, Ralph; Subbiah, Vivek; Fu, Siqing; Schwab, Richard; Moulder, Stacy; Valero, Vicente; Schwaederle, Maria; Yelensky, Roman; Miller, Vincent A; Stephens, M Philip J; Meric-Bernstam, Funda; Kurzrock, Razelle

    2014-05-15

    Our analysis of the tumors of 57 women with metastatic breast cancer with next generation sequencing (NGS) demonstrates that each patient's tumor is unique in its molecular fingerprint. We observed 216 somatic aberrations in 70 different genes, including 131 distinct aberrations. The most common gene alterations (in order of decreasing frequency) included: TP53, PIK3CA, CCND1, MYC, HER2 (ERBB2), MCL1, PTEN, FGFR1, GATA3, NF1, PIK3R1, BRCA2, EGFR, IRS2, CDH1, CDKN2A, FGF19, FGF3 and FGF4. Aberrations included mutations (46%), amplifications (45%), deletions (5%), splices (2%), truncations (1%), fusions (0.5%) and rearrangements (0.5%), with multiple distinct variants within the same gene. Many of these aberrations represent druggable targets, either through direct pathway inhibition or through an associated pathway (via 'crosstalk'). The 'molecular individuality' of these tumors suggests that a customized strategy, using an "N-of-One" model of precision medicine, may represent an optimal approach for the treatment of patients with advanced tumors.

  18. Mutational myriad of tumor suppressor p53 in Filipino breast cancer: results and perspectives in molecular pathology and epidemiology

    International Nuclear Information System (INIS)

    Deocaris, Custer C.

    2000-04-01

    The p53 tumor suppressor is by far the most widely mutated gene in human cancers. p53 encodes a 53-kDa phosphoprotein, transcription-activator whose targets include genes and gene products that orchestrate genomic stability, cellular response to DNA damage, cell cycle progression apoptosis and aging (senescence). Analysis of the p53 gene profile has previously resulted in identifying several cancer-causative factors in the human setting, as well as, in creating a unique molecular profile of a tumor useful in the design of tailored-therapies for individual cancer patients. Our results in screening for p53 abnormalities in 140 Filipino patients with primary breast lesions confined from 1997-1998 in 5 major hospitals in Manila reveal that p53 plays an important role in the development and progression of breast cancer in at least 48% of all cases. Two methods of p53 analysis are employed, enzyme-linked immunosorbent assay (ELISA) and polymerase chain reaction-temporal temperature gradient electrophoresis (PCR-TTGE). Inter-comparisons of method exhibit 63.3% concordance in 21 fresh breast carcinoma samples, with ELISA demonstrating 14% false-positives and 10% false-negatives. Only mutations in exon 7 (p=0.063) in the tumor samples how significant correlation with abnormal cellular elevation of p53. PCR-TTGE screening in a large series of 140 patients show that most genetic lesions are localized in exons 5 (41% of the total cases) and 6 (27% of the total cases). No mutations are, however, detected in the transactivation (exons 2-4) and oligomerization (exons 10-11) domains. Invasive carcinomas (stages II and III) are characterized with more frequent and diverse genetic alterations compared with benign tumors, most significantly at exon 5B (p=0.066) and at independently multiple sites (p=0.066). Earlier-onset cases (age of diagnosis < 50 yrs), known to be more clinico-pathologically aggressive, are diagnosed harboring more frequent p53 mutations centered at exon 7 (p=0

  19. Mutational myriad of tumor suppressor p53 in Filipino breast cancer: results and perspectives in molecular pathology and epidemiology

    Energy Technology Data Exchange (ETDEWEB)

    Deocaris, Custer C

    2000-04-01

    The p53 tumor suppressor is by far the most widely mutated gene in human cancers. p53 encodes a 53-kDa phosphoprotein, transcription-activator whose targets include genes and gene products that orchestrate genomic stability, cellular response to DNA damage, cell cycle progression apoptosis and aging (senescence). Analysis of the p53 gene profile has previously resulted in identifying several cancer-causative factors in the human setting, as well as, in creating a unique molecular profile of a tumor useful in the design of tailored-therapies for individual cancer patients. Our results in screening for p53 abnormalities in 140 Filipino patients with primary breast lesions confined from 1997-1998 in 5 major hospitals in Manila reveal that p53 plays an important role in the development and progression of breast cancer in at least 48% of all cases. Two methods of p53 analysis are employed, enzyme-linked immunosorbent assay (ELISA) and polymerase chain reaction-temporal temperature gradient electrophoresis (PCR-TTGE). Inter-comparisons of method exhibit 63.3% concordance in 21 fresh breast carcinoma samples, with ELISA demonstrating 14% false-positives and 10% false-negatives. Only mutations in exon 7 (p=0.063) in the tumor samples how significant correlation with abnormal cellular elevation of p53. PCR-TTGE screening in a large series of 140 patients show that most genetic lesions are localized in exons 5 (41% of the total cases) and 6 (27% of the total cases). No mutations are, however, detected in the transactivation (exons 2-4) and oligomerization (exons 10-11) domains. Invasive carcinomas (stages II and III) are characterized with more frequent and diverse genetic alterations compared with benign tumors, most significantly at exon 5B (p=0.066) and at independently multiple sites (p=0.066). Earlier-onset cases (age of diagnosis < 50 yrs), known to be more clinico-pathologically aggressive, are diagnosed harboring more frequent p53 mutations centered at exon 7 (p=0

  20. Breast Cancer Mortality in African-American and Non-Hispanic White Women by Molecular Subtype and Stage at Diagnosis: A Population-Based Study.

    Science.gov (United States)

    Tao, Li; Gomez, Scarlett Lin; Keegan, Theresa H M; Kurian, Allison W; Clarke, Christina A

    2015-07-01

    Higher breast cancer mortality rates for African-American than non-Hispanic White women are well documented; however, it remains uncertain if this disparity occurs in disease subgroups defined by tumor molecular markers and stage at diagnosis. We examined racial differences in outcome according to subtype and stage in a diverse, population-based series of 103,498 patients. We obtained data for all invasive breast cancers diagnosed between January 1, 2005, and December 31, 2012, and followed through December 31, 2012, among 93,760 non-Hispanic White and 9,738 African-American women in California. Molecular subtypes were categorized according to tumor expression of hormone receptor (HR, based on estrogen and progesterone receptors) and human epidermal growth factor receptor 2 (HER2). Cox proportional hazards models were used to calculate relative hazard (RH) and 95% confidence intervals (CI) for breast cancer-specific mortality. After adjustment for patient, tumor, and treatment characteristics, outcomes were comparable by race for stage I or IV cancer regardless of subtype, and HR(+)/HER2(+) or HR(-)/HER2(+) cancer regardless of stage. We found substantially higher hazards of breast cancer death among African-American women with stage II/III HR(+)/HER2(-) (RH, 1.31; 95% CI, 1.03-1.65; and RH, 1.39; 95% CI, 1.10-1.75, respectively) and stage III triple-negative cancers relative to Whites. There are substantial racial/ethnic disparities among patients with stages II/III HR(+)/HER2(-) and stage III triple-negative breast cancers but not for other subtype and stage. These data provide insights to assess barriers to targeted treatment (e.g., trastuzumab or endocrine therapy) of particular subtypes of breast cancer among African-American patients. ©2015 American Association for Cancer Research.

  1. Relationship between the inflammatory molecular profile of breast carcinomas and distant metastasis development.

    Directory of Open Access Journals (Sweden)

    Noemí Eiró

    Full Text Available Inflammatory conditions may promote tumor progression and aggressiveness. In previous reports, we found a group of breast cancer tumors characterized by metalloprotease-11 (MMP-11 expression by intratumoral mononuclear inflammatory cells (MICs, which was associated with distant metastasis development. Thus, in the present study we evaluated the relationship between MMP-11 expression by MICs, distant metastasis development, and a wide panel of inflammatory factors in breast carcinoma. In an initial approach, we analyzed 65 factors associated with tumor progression and inflammation, in a tumor population classified in good or bad prognosis, based on MMP-11 expression by intratumoral MICs. The most differentially expressed factors were then analyzed in a wider tumor population classified according to MMP-11 expression by MICs and also according to metastasis development. These analyses were carried out by Real-time PCR. The results showed that of the 65 starting factors analyzed, those related with MMP-11 expression by MICs were: IL-1, -5, -6, -8, -17, -18, MMP-1, TIMP-1, ADAM-8, -10, -15, -23, ADAMTS-1, -2, -15, Annexin A2, IFNβ, Claudin-3, CCL-3, MyD88, IRAK-4 and NFκB. Of them, factors more differentially expressed between both groups of tumors were IL-1, IL-5, IL-6, IL-17, IFNβ and NFκB. Thereafter, we confirmed in the wider tumor population, that there is a higher expression of those factors in tumors infiltrated by MMP-11 positive MICs. Altogether these results indicate that tumors developing worse prognosis and identified by MMP-11 expression by intratumoral MICs, shows an up-regulation of inflammatory-related genes.

  2. Validation of the prognostic gene portfolio, ClinicoMolecular Triad Classification, using an independent prospective breast cancer cohort and external patient populations.

    Science.gov (United States)

    Wang, Dong-Yu; Done, Susan J; Mc Cready, David R; Leong, Wey L

    2014-07-04

    Using genome-wide expression profiles of a prospective training cohort of breast cancer patients, ClinicoMolecular Triad Classification (CMTC) was recently developed to classify breast cancers into three clinically relevant groups to aid treatment decisions. CMTC was found to be both prognostic and predictive in a large external breast cancer cohort in that study. This study serves to validate the reproducibility of CMTC and its prognostic value using independent patient cohorts. An independent internal cohort (n = 284) and a new external cohort (n = 2,181) were used to validate the association of CMTC between clinicopathological factors, 12 known gene signatures, two molecular subtype classifiers, and 19 oncogenic signalling pathway activities, and to reproduce the abilities of CMTC to predict clinical outcomes of breast cancer. In addition, we also updated the outcome data of the original training cohort (n = 147). The original training cohort reached a statistically significant difference (p value of the triad classification was reproduced in the second independent internal cohort and the new external validation cohort. CMTC achieved even higher prognostic significance when all available patients were analyzed (n = 4,851). Oncogenic pathways Myc, E2F1, Ras and β-catenin were again implicated in the high-risk groups. Both prospective internal cohorts and the independent external cohorts reproduced the triad classification of CMTC and its prognostic significance. CMTC is an independent prognostic predictor, and it outperformed 12 other known prognostic gene signatures, molecular subtype classifications, and all other standard prognostic clinicopathological factors. Our results support further development of CMTC portfolio into a guide for personalized breast cancer treatments.

  3. Luminal B tumors are the most frequent molecular subtype in breast cancer of North African women: an immunohistochemical profile study from Morocco

    Directory of Open Access Journals (Sweden)

    El Fatemi Hinde

    2012-12-01

    Full Text Available Abstract Background Breast cancer may be classified into luminal A, luminal B, HER2+/ER-, basal-like and normal-like subtypes based on gene expression profiling or immunohistochemical (IHC characteristics. The aim of our study is to show the molecular profile characteristic of breast cancer in the North African population of Morocco. This work showed preliminary results and correlations with clinicopathological and histological parameters. Three hundred and ninety primary breast carcinomas tumor tissues were immunostained for ER, PR, HER2, CK5/6, CK8/18 and Ki67 using paraffin tissue. Methods We reviewed 390 cases of breast cancer diagnosed on January 2008 to December 2011 at the Department of pathology, Hassan II teaching hospital, Fez, Morocco. Age, size tumor, metastatic profile, node involvement profile, histological type and immunohistochemical profile were studied. Results The average age was 46 years; our patients were diagnosed late with a high average tumor size. Luminal B subtype was more prevalent (41.8%, followed by luminal A (30.5%, basal-like (13, 6%, Her2-overexpressing (9, 2%, and unclassified subtype (4.9%. Conclusion This study showed that molecular classification and biological profile may be different according to geographical distribution, to encourage further studies to know the genomic profile of tumors and the environment. Virtual slide http://www.diagnosticpathology.diagnomx.eu/vs/1675272504826544

  4. Study of the Expression of Survivin & Its Splice Variants; ΔEx3, 2b and 3b as Diagnostic Molecular Markers in Breast Cancer

    Directory of Open Access Journals (Sweden)

    E Babaei

    2009-07-01

    Full Text Available Introduction: Survivin is a new member of the Inhibitor Apotosis Protein family (IAP which plays an important role in the regulation of both cell cycle and apoptosis. Its distinct expression in tumor cells as compared to normal adult cells introduces Survivin as the fourth transcriptom demonstrated in tumors. Breast cancer is the most common malignancy among women and scientist`s efforts to classify it has lead to various molecular subtypes and controversial results. Because of the high prevalence of these tumors and lack of suitable molecular markers for diagnosis and prognosis, there are ongoing efforts to find molecular markers which can distinguish nontumoral from tumor tissues. In this study we evaluate the potential usefulness of Survivin and its splice variants ΔEx3, 2b and 3b as molecular markers in breast cancer. Methods: We studied 18 tumor and 17 non tumor adjacent tissues. Transcription levels were measured by Semiquantitative Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR and normalized by ß2m as an internal control. Results: 1Survivin and its splice variants; Δex3, 2b and 3b showed differentially higher expression levels in tumors than adjacent normal tissues. 2 The expression levels of Survivin, Survivin-ΔEx3 and Survivin-3b were significantly correlated with the type of tumors. 3 Survivin-2b was expressed in a few samples. 4 Survivin-3b was detected only in tumor samples. Also, our results showed that ΔEx3 variant can be introduced as a dominant expressed variant in breast cancer. Conclusion: Our data indicated that the expression of Survivin, Survivin ∆Ex3 and especially, Survivin-3b were correlated with cancerous nature of tumors and Survivin-∆Ex3 was the most common expressed variant in breast carcinomas. These results besides confirming the potential usefulness of Survivin and its splice variants as molecular markers in breast cancer, demonstrated the role of the gene and its splice variants, especially 3b

  5. Molecular essence and endocrine responsiveness of estrogen receptor-negative, progesterone receptor-positive, and HER2-negative breast cancer.

    Science.gov (United States)

    Yu, Ke-Da; Jiang, Yi-Zhou; Hao, Shuang; Shao, Zhi-Ming

    2015-10-05

    The clinical significance of progesterone receptor (PgR) expression in estrogen receptor-negative (ER-) breast cancer is controversial. Herein, we systemically investigate the clinicopathologic features, molecular essence, and endocrine responsiveness of ER-/PgR+/HER2- phenotype. Four study cohorts were included. The first and second cohorts were from the Surveillance, Epidemiology, and End Results database (n = 67,932) and Fudan University Shanghai Cancer Center (n = 2,338), respectively, for clinicopathologic and survival analysis. The third and fourth cohorts were from two independent publicly available microarray datasets including 837 operable cases and 483 cases undergoing neoadjuvant chemotherapy, respectively, for clinicopathologic and gene-expression analysis. Characterized genes defining subgroups within the ER-/PgR+/HER2- phenotype were determined and further validated. Clinicopathologic features and survival outcomes of the ER-/PgR+ phenotype fell in between the ER+/PgR+ and ER-/PgR- phenotypes, but were more similar to ER-/PgR-. Among the ER-/PgR+ phenotype, 30% (95% confidence interval [CI] 17-42%, pooled by a fixed-effects method) were luminal-like and 59% (95% CI 45-72%, pooled by a fixed-effects method) were basal-like. We further refined the characterized genes for subtypes within the ER-/PgR+ phenotype and developed an immunohistochemistry-based method that could determine the molecular essence of ER-/PgR+ using three markers, TFF1, CK5, and EGFR. Either PAM50-defined or immunohistochemistry-defined basal-like ER-/PgR+ cases have a lower endocrine therapy sensitivity score compared with luminal-like ER-/PgR+ cases (P defined basal-like ER-/PgR+ cases might not benefit from adjuvant endocrine therapy (log-rank P = 0.61 for sufficient versus insufficient endocrine therapy). The majority of ER-/PgR+/HER2- phenotype breast cancers are basal-like and associated with a lower endocrine therapy sensitivity score. Additional studies are needed

  6. Selected Aspects of Molecular Diagnostics of Constitutional Alterations in BRCA1 and BRCA2 Genes Associated with Increased Risk of Breast Cancer in the Polish Population

    Directory of Open Access Journals (Sweden)

    Górski Bohdan

    2006-08-01

    discovered in 8.1% and NBS1 mutation (657del5 in 0.8% of the patients. The changes were more frequent in the study than the control group. However, the risk of breast cancer was significantly higher for only three of them. Two changes, namely 5382insC and C61G of the BRCA1 gene revealed a high penetrance (OR 6.2 and 15.0, respectively, while I157T of the CHEK2 gene was associated with a low risk of breast cancer (OR 1.4. Mutations of the BRCA1, CHEK2 and NSB1 genes were significantly more frequent in patients with breast cancer diagnosed prior to 50 years of age. The mean age at diagnosis was 47.2 years for carriers of the BRCA1 mutation, 50.7 years for NBS1 and 54.2 for CHEK2. The mean age at diagnosis in the group of patients without any if the mutations described above was 56.1 years. When breast cancer patients with the diagnosis before and after 50 years of age were compared, the greatest difference in the frequency of mutation was revealed for the BRCA1 gene (5.5% vs 1.5%. BRCA1 mutations were significantly more frequent I familial aggregates of the tumor (10.8%, but were also present in sporadic cases (1.8%. For the CHEK2 and NBS1 genes, there was no correlation between frequency and family history of cancer in probands. 5. A higher frequency of heterozygous carriers of 5972C/T polymorphism of the BRCA2 gene was demonstrated for breast cancer prior to 50 years of age (OR 1.4. the risk of breast cancer prior to 50 years of age was particularly high in 5972T/T homozygote (OR 4.7. This polymorphism was associated with breast cancer notable for intraductal growth. Conclusions 1. Efficient molecular diagnostics of genetic predisposition to breast/ovarian cancer in Poland could be based on relatively simple tests disclosing some of the most frequent recurrent mutations of the BRCA1 gene. 2. The risk of breast cancer seems to be only slightly higher in carriers of some BRCA1 gene mutations. This finding should be taken into account during work on prevention schemes for

  7. New insights into the metastatic behavior after breast cancer surgery, according to well-established clinicopathological variables and molecular subtypes.

    Directory of Open Access Journals (Sweden)

    Oreste Claudio Buonomo

    Full Text Available Despite advances in treatment, up to 30% of patients with early breast cancer (BC experience distant disease relapse. However, a comprehensive understanding of tumor spread and site-specific recurrence patterns remains lacking. This retrospective case-control study included 103 consecutive patients with metastatic BC admitted to our institution (2000-2013. Cases were matched according to age, tumor biology, and clinicopathological features to 221 patients with non-metastatic BC (control group. The median follow-up period among the 324 eligible patients was 7.3 years. While relatively low values for sensitivity (71% and specificity (56% were found for axillary lymph node (ALN involvement as an indicator of risk and pattern of distant relapse, nodal status remained the most powerful predictor of metastases (OR: 3.294; CL: 1.9-5.5. Rates of dissemination and metastatic efficiency differed according to molecular subtype. HER2-positive subtypes showed a stronger association with systemic spread (OR: 2.127; CL: 1.2-3.8 than other subgroups. Classification as Luminal or Non-Luminal showed an increased risk of lung and distant nodal recurrence, and a decreased risk in bone metastases in the Non-Luminal group (OR: 2.9, 3.345, and 0.2, respectively. Tumors with HER2 overexpression had a significantly high risk for distant relapse (OR: 2.127 compared with HER2-negative tumors and also showed higher central nervous system (CNS and lung metastatic potential (OR: 5.6 and 2.65, respectively and low risk of bone disease progression (OR: 0.294. Furthermore, we found significant associations between biological profiles and sites of recurrence. A new process of clinical/diagnostic staging, including molecular subtypes, could better predict the likelihood of distant relapses and their anatomical location. Recognition and appreciation of clinically distinct molecular subtypes may assist in evaluation of the probability of distant relapses and their sites. Our

  8. Clinical application of a microfluidic chip for immunocapture and quantification of circulating exosomes to assist breast cancer diagnosis and molecular classification.

    Science.gov (United States)

    Fang, Shimeng; Tian, Hongzhu; Li, Xiancheng; Jin, Dong; Li, Xiaojie; Kong, Jing; Yang, Chun; Yang, Xuesong; Lu, Yao; Luo, Yong; Lin, Bingcheng; Niu, Weidong; Liu, Tingjiao

    2017-01-01

    Increasing attention has been attracted by exosomes in blood-based diagnosis because cancer cells release more exosomes in serum than normal cells and these exosomes overexpress a certain number of cancer-related biomarkers. However, capture and biomarker analysis of exosomes for clinical application are technically challenging. In this study, we developed a microfluidic chip for immunocapture and quantification of circulating exosomes from small sample volume and applied this device in clinical study. Circulating EpCAM-positive exosomes were measured in 6 cases breast cancer patients and 3 healthy controls to assist diagnosis. A significant increase in the EpCAM-positive exosome level in these patients was detected, compared to healthy controls. Furthermore, we quantified circulating HER2-positive exosomes in 19 cases of breast cancer patients for molecular classification. We demonstrated that the exosomal HER2 expression levels were almost consistent with that in tumor tissues assessed by immunohistochemical staining. The microfluidic chip might provide a new platform to assist breast cancer diagnosis and molecular classification.

  9. Multiparametric and molecular imaging of breast tumors with MRI and PET/MRI; Multiparametrische und molekulare Bildgebung von Brusttumoren mit MRT und PET-MRT

    Energy Technology Data Exchange (ETDEWEB)

    Pinker, K. [Medizinische Universitaet Wien, Universitaetsklinik fuer Radiologie und Nuklearmedizin, Division fuer Molekulare und Gender Bildgebung, Wien (Austria); Memorial Sloan-Kettering Cancer Center, Department of Radiology, Molecular Imaging and Therapy Service, New York (United States); State University of Florida, Department of Scientific Computing in Medicine, Florida (United States); Marino, M.A. [Medizinische Universitaet Wien, Universitaetsklinik fuer Radiologie und Nuklearmedizin, Division fuer Molekulare und Gender Bildgebung, Wien (Austria); Policlinico Universitario G. Martino, University of Messina, Department of Biomedical Sciences and Morphologic and Functional Imaging, Messina (Italy); Meyer-Baese, A. [State University of Florida, Department of Scientific Computing in Medicine, Florida (United States); Helbich, T.H. [Medizinische Universitaet Wien, Universitaetsklinik fuer Radiologie und Nuklearmedizin, Division fuer Molekulare und Gender Bildgebung, Wien (Austria)

    2016-07-15

    Magnetic resonance imaging (MRI) of the breast is an indispensable tool in breast imaging for many indications. Several functional parameters with MRI and positron emission tomography (PET) have been assessed for imaging of breast tumors and their combined application is defined as multiparametric imaging. Available data suggest that multiparametric imaging using different functional MRI and PET parameters can provide detailed information about the hallmarks of cancer and may provide additional specificity. Multiparametric and molecular imaging of the breast comprises established MRI parameters, such as dynamic contrast-enhanced MRI, diffusion-weighted imaging (DWI), MR proton spectroscopy ({sup 1}H-MRSI) as well as combinations of radiological and MRI techniques (e.g. PET/CT and PET/MRI) using radiotracers, such as fluorodeoxyglucose (FDG). Multiparametric and molecular imaging of the breast can be performed at different field-strengths (range 1.5-7 T). Emerging parameters comprise novel promising techniques, such as sodium imaging ({sup 23}Na MRI), phosphorus spectroscopy ({sup 31}P-MRSI), chemical exchange saturation transfer (CEST) imaging, blood oxygen level-dependent (BOLD) and hyperpolarized MRI as well as various specific radiotracers. Multiparametric and molecular imaging has multiple applications in breast imaging. Multiparametric and molecular imaging of the breast is an evolving field that will enable improved detection, characterization, staging and monitoring for personalized medicine in breast cancer. (orig.) [German] Die Magnetresonanztomographie (MRT) der Brust ist ein etabliertes nichtinvasives bildgebendes Verfahren mit vielfaeltigen Indikationen. In den letzten Jahren wurden zahlreiche funktionelle MRT- und Positronenemissionstomographie(PET)-Parameter in der Brustbildgebung evaluiert, und ihre kombinierte Anwendung ist als multiparametrische Bildgebung definiert. Bisherige Daten legen nahe, dass die multiparametrische Bildgebung mit MRT und PET

  10. Design, synthesis and molecular modeling of new 4-phenylcoumarin derivatives as tubulin polymerization inhibitors targeting MCF-7 breast cancer cells.

    Science.gov (United States)

    Batran, Rasha Z; Kassem, Asmaa F; Abbas, Eman M H; Elseginy, Samia A; Mounier, Marwa M

    2018-07-23

    A new set of 4-phenylcoumarin derivatives was designed and synthesized aiming to introduce new tubulin polymerization inhibitors as anti-breast cancer candidates. All the target compounds were evaluated for their cytotoxic effects against MCF-7 cell line, where compounds 2f, 3a, 3b, 3f, 7a and 7b, showed higher cytotoxic effect (IC 50  = 4.3-21.2 μg/mL) than the reference drug doxorubicin (IC 50  = 26.1 μg/mL), additionally, compounds 1 and 6b exhibited the same potency as doxorubicin (IC 50  = 25.2 and 28.0 μg/mL, respectively). The thiazolidinone derivatives 3a, 3b and 3f with potent and selective anticancer effects towards MCF-7 cells (IC 50  = 11.1, 16.7 and 21.2 μg/mL) were further assessed for tubulin polymerization inhibition effects which showed that the three compounds were potent tubulin polymerization suppressors with IC 50 values of 9.37, 2.89 and 6.13 μM, respectively, compared to the reference drug colchicine (IC 50  = 6.93 μM). The mechanistic effects on cell cycle progression and induction of apoptosis in MCF-7 cells were determined for compound 3a due to its potent and selective cytotoxic effects in addition to its promising tubulin polymerization inhibition potency. The results revealed that compound 3a induced cell cycle cessation at G2/M phase and accumulation of cells in pre-G1 phase and prevented its mitotic cycle, in addition to its activation of caspase-7 mediating apoptosis of MCF-7 cells. Molecular modeling studies for compounds 3a, 3b and 3f were carried out on tubulin crystallography, the results indicated that the compounds showed binding mode similar to the co-crystalized ligand; colchicine. Moreover, pharmacophore constructed models and docking studies revealed that thiazolidinone, acetamide and coumarin moieties are crucial for the activity. Molecular dynamics (MD) studies were carried out for the three compounds over 100 ps. MD results of compound 3a showed that it reached the stable state

  11. Evaluation of the BreastSimulator software platform for breast tomography

    Science.gov (United States)

    Mettivier, G.; Bliznakova, K.; Sechopoulos, I.; Boone, J. M.; Di Lillo, F.; Sarno, A.; Castriconi, R.; Russo, P.

    2017-08-01

    The aim of this work was the evaluation of the software BreastSimulator, a breast x-ray imaging simulation software, as a tool for the creation of 3D uncompressed breast digital models and for the simulation and the optimization of computed tomography (CT) scanners dedicated to the breast. Eight 3D digital breast phantoms were created with glandular fractions in the range 10%-35%. The models are characterised by different sizes and modelled realistic anatomical features. X-ray CT projections were simulated for a dedicated cone-beam CT scanner and reconstructed with the FDK algorithm. X-ray projection images were simulated for 5 mono-energetic (27, 32, 35, 43 and 51 keV) and 3 poly-energetic x-ray spectra typically employed in current CT scanners dedicated to the breast (49, 60, or 80 kVp). Clinical CT images acquired from two different clinical breast CT scanners were used for comparison purposes. The quantitative evaluation included calculation of the power-law exponent, β, from simulated and real breast tomograms, based on the power spectrum fitted with a function of the spatial frequency, f, of the form S(f)  =  α/f   β . The breast models were validated by comparison against clinical breast CT and published data. We found that the calculated β coefficients were close to that of clinical CT data from a dedicated breast CT scanner and reported data in the literature. In evaluating the software package BreastSimulator to generate breast models suitable for use with breast CT imaging, we found that the breast phantoms produced with the software tool can reproduce the anatomical structure of real breasts, as evaluated by calculating the β exponent from the power spectral analysis of simulated images. As such, this research tool might contribute considerably to the further development, testing and optimisation of breast CT imaging techniques.

  12. Outcome disparities in African American women with triple negative breast cancer: a comparison of epidemiological and molecular factors between African American and Caucasian women with triple negative breast cancer

    International Nuclear Information System (INIS)

    Sturtz, Lori A; Melley, Jen; Mamula, Kim; Shriver, Craig D; Ellsworth, Rachel E

    2014-01-01

    Although diagnosed less often, breast cancer in African American women (AAW) displays different characteristics compared to breast cancer in Caucasian women (CW), including earlier onset, less favorable clinical outcome, and an aggressive tumor phenotype. These disparities may be attributed to differences in socioeconomic factors such as access to health care, lifestyle, including increased frequency of obesity in AAW, and tumor biology, especially the higher frequency of triple negative breast cancer (TNBC) in young AAW. Improved understanding of the etiology and molecular characteristics of TNBC in AAW is critical to determining whether and how TNBC contributes to survival disparities in AAW. Demographic, pathological and survival data from AAW (n = 62) and CW (n = 98) with TNBC were analyzed using chi-square analysis, Student’s t-tests, and log-rank tests. Frozen tumor specimens were available from 57 of the TNBC patients (n = 23 AAW; n = 34 CW); RNA was isolated after laser microdissection of tumor cells and was hybridized to HG U133A 2.0 microarrays. Data were analyzed using ANOVA with FDR <0.05, >2-fold difference defining significance. The frequency of TNBC compared to all BC was significantly higher in AAW (28%) compared to CW (12%), however, significant survival and pathological differences were not detected between populations. Gene expression analysis revealed the tumors were more similar than different at the molecular level, with only CRYBB2P1, a pseudogene, differentially expressed between populations. Among demographic characteristics, AAW consumed significantly lower amounts of caffeine and alcohol, were less likely to breastfeed and more likely to be obese. These data suggest that TNBC in AAW is not a unique disease compared to TNBC in CW. Rather, higher frequency of TNBC in AAW may, in part, be attributable to the effects of lifestyle choices. Because these risk factors are modifiable, they provide new opportunities for the development of risk

  13. Department of Defense Era of Hope Scholar Award Nanotechnology-Enabled Optical Molecular Imaging of Breast Cancer

    Science.gov (United States)

    2009-07-01

    detection, and management of breast cancer today. A variety of imaging methods including screening and diagnostic x- ray mammography and resonance...profile of a tumor. In addition, techniques such as x- ray imaging and MRI are not able to detect small early cancers or pre-cancerous breast...227 (2007). 18. S. Oldenburg , J. Jackson, S. Westcott, and N. Halas, “Infrared extinction properties of gold nanoshells,” Appl. Phys. Lett. 75, 2897

  14. The prognostic role of 99mTc-MDP breast scintigraphy. Comparison of scintigrafic findings with histologic and molecular parameters

    International Nuclear Information System (INIS)

    Dimonte, M.; Leo, G.; Marsigliante, S.

    1999-01-01

    Breast scintigraphy (BS) with the bone-seeking agent 99m Tc-medronate (MDP) can be usefully combined with mammography to diagnose and characterize questionable breast lumps. However this radiotracer does not seem to provide any further prognostic information about breast cancer. Therefore it is investigated the prognostic yield of MDP-BS searching for correlations between scintigraphic findings and the major biological and histologic parameters. It is retrospectively analyzed a series of 44 primary breast cancers. All patients had undergone 99m Tc-MDP bone scan for preoperative staging, as well as conventional breast imaging. It is statistically compared the cancer/background ratio (c/b index) with lesion histotype, diameter, grading, and the tissue concentrations of steroid receptors, cathepsine D, type 1 timidine kinase, pS2 and p53 proteins). Differently from BS with 99m Tc-MIBI, 201 Tl, 18 F-FDG, 111 In-OCT and radiolabeled estrogens and despite its good overall accuracy, MDP-BS appears to have no prognostic role. In fact, despite the well-known capability of soft tissue lesions to take up the tracer, MDP tumor trapping seems to depend mainly on the increased permeability of neo vessels and on interstitial space enlargement. Few reports are available in the literature on the correlation between in vivo MDP uptake by the breast cancer and prognostic parameters. Thus, it are tested possible correlations between the amount of MDP taken up by the breast cancer, histologic features and cell concentrations of some major biomarkers. The lack of any statistical significance is in agreement with the theory, and confirms the little prognostic value of MDP-BS. Nevertheless, further trials are warranted on larger series of cases to validate personal findings [it

  15. Long-term use of metformin and the molecular subtype in invasive breast carcinoma patients – a retrospective study of clinical and tumor characteristics

    International Nuclear Information System (INIS)

    Besic, Nikola; Satej, Nika; Ratosa, Ivica; Horvat, Andreja Gojkovic; Marinko, Tanja; Gazic, Barbara; Petric, Rok

    2014-01-01

    Metformin may exhibit inhibitory effects on cancer cells by inhibiting mTOR signaling pathway. The aim of our retrospective study was to examine if patients with breast carcinoma (BC) and diabetes mellitus (DM) receiving metformin have a lower stage of carcinoma in comparison to patients not receiving metformin, and if the use of metformin correlates with the molecular subtype of BC. A chart review of 253 patients with invasive BC and DM (128 on metformin and 125 not on metformin) was performed. Control group consisted of 320 consecutive patients with invasive BC without DM. BC subtypes were classified by immunohistochemical surrogates as luminal A (estrogen receptor [ER] + and/or progesterone receptor [PR]+, HER-2-), luminal B (ER + and/or PR+, HER-2+), HER-2 (ER-, PR-, HER-2+), triple-negative/basal (ER-, PR-, HER-2-). Patients on metformin had a lower proportion of T3 or T4 tumors than patients who were not receiving metformin (16% vs. 26%; p = 0.035). No statistical difference was found between the two study groups in N stage. Patients with DM on metformin, with DM not on metformin and the control group had different molecular subtypes of BC (p = 0.01): the luminal A subtype was found in 78%, 83% and 71%, the luminal B in 12.6%, 9% and 11%, HER-2 in 0.8%, 1.6% and 8%, and the triple-negative/basal-like subtype in 8.6%, 6.4% and 10%, respectively. Our data indicate that long-term use of metformin use correlates with molecular subtype of BC in diabetics on metformin in comparison to diabetics not on metformin and patients without DM. However, most likely, different distribution of the molecular subtypes of BC in these three groups of patients was caused by other risk factors for breast carcinoma, such as age of patients or obesity

  16. Novel cancer gene variants and gene fusions of triple-negative breast cancers (TNBCs) reveal their molecular diversity conserved in the patient-derived xenograft (PDX) model.

    Science.gov (United States)

    Jung, Jaeyun; Jang, Kiwon; Ju, Jung Min; Lee, Eunji; Lee, Jong Won; Kim, Hee Jung; Kim, Jisun; Lee, Sae Byul; Ko, Beom Seok; Son, Byung Ho; Lee, Hee Jin; Gong, Gyungyup; Ahn, Sei Yeon; Choi, Jung Kyoon; Singh, Shree Ram; Chang, Suhwan

    2018-04-20

    Despite the improved 5-year survival rate of breast cancer, triple-negative breast cancer (TNBC) remains a challenge due to lack of effective targeted therapy and higher recurrence and metastasis than other subtypes. To identify novel druggable targets and to understand its unique biology, we tried to implement 24 patient-derived xenografts (PDXs) of TNBC. The overall success rate of PDX implantation was 45%, much higher than estrogen receptor (ER)-positive cases. Immunohistochemical analysis revealed conserved ER/PR/Her2 negativity (with two exceptions) between the original and PDX tumors. Genomic analysis of 10 primary tumor-PDX pairs with Ion AmpliSeq CCP revealed high degree of variant conservation (85.0% to 96.9%) between primary and PDXs. Further analysis showed 44 rare variants with a predicted high impact in 36 genes including Trp53, Pten, Notch1, and Col1a1. Among them, we confirmed frequent Notch1 variant. Furthermore, RNA-seq analysis of 24 PDXs revealed 594 gene fusions, of which 163 were in-frame, including AZGP1-GJC3 and NF1-AARSD1. Finally, western blot analysis of oncogenic signaling proteins supporting molecular diversity of TNBC PDXs. Overall, our report provides a molecular basis for the usefulness of the TNBC PDX model in preclinical study. Copyright © 2018. Published by Elsevier B.V.

  17. Prognostic Value of Molecular Subtypes, Ki67 Expression and Impact of Postmastectomy Radiation Therapy in Breast Cancer Patients With Negative Lymph Nodes After Mastectomy

    Energy Technology Data Exchange (ETDEWEB)

    Selz, Jessica, E-mail: chaumontjessica@yahoo.fr [Department of Radiation Oncology, Institut Curie, Hopital Rene Huguenin, Saint Cloud (France); Stevens, Denise; Jouanneau, Ludivine [Department of Medical Statistics, Institut Curie, Hopital Rene Huguenin, Saint Cloud (France); Labib, Alain [Department of Radiation Oncology, Institut Curie, Hopital Rene Huguenin, Saint Cloud (France); Le Scodan, Romuald [Department of Radiation Oncology, Centre Hospitalier Prive Saint Gregoire, Saint Gregoire (France)

    2012-12-01

    Purpose: To determine whether Ki67 expression and breast cancer subtypes could predict locoregional recurrence (LRR) and influence the postmastectomy radiotherapy (PMRT) decision in breast cancer (BC) patients with pathologic negative lymph nodes (pN0) after modified radical mastectomy (MRM). Methods and Materials: A total of 699 BC patients with pN0 status after MRM, treated between 2001 and 2008, were identified from a prospective database in a single institution. Tumors were classified by intrinsic molecular subtype as luminal A or B, HER2+, and triple-negative (TN) using estrogen, progesterone, and HER2 receptors. Multivariate Cox analysis was used to determine the risk of LRR associated with intrinsic subtypes and Ki67 expression, adjusting for known prognostic factors. Results: At a median follow-up of 56 months, 17 patients developed LRR. Five-year LRR-free survival and overall survival in the entire population were 97%, and 94.7%, respectively, with no difference between the PMRT (n=191) and no-PMRT (n=508) subgroups. No constructed subtype was associated with an increased risk of LRR. Ki67 >20% was the only independent prognostic factor associated with increased LRR (hazard ratio, 4.18; 95% CI, 1.11-15.77; P<.0215). However, PMRT was not associated with better locoregional control in patients with proliferative tumors. Conclusions: Ki67 expression but not molecular subtypes are predictors of locoregional recurrence in breast cancer patients with negative lymph nodes after MRM. The benefit of adjuvant RT in patients with proliferative tumors should be further investigated in prospective studies.

  18. Prognostic Value of Molecular Subtypes, Ki67 Expression and Impact of Postmastectomy Radiation Therapy in Breast Cancer Patients With Negative Lymph Nodes After Mastectomy

    International Nuclear Information System (INIS)

    Selz, Jessica; Stevens, Denise; Jouanneau, Ludivine; Labib, Alain; Le Scodan, Romuald

    2012-01-01

    Purpose: To determine whether Ki67 expression and breast cancer subtypes could predict locoregional recurrence (LRR) and influence the postmastectomy radiotherapy (PMRT) decision in breast cancer (BC) patients with pathologic negative lymph nodes (pN0) after modified radical mastectomy (MRM). Methods and Materials: A total of 699 BC patients with pN0 status after MRM, treated between 2001 and 2008, were identified from a prospective database in a single institution. Tumors were classified by intrinsic molecular subtype as luminal A or B, HER2+, and triple-negative (TN) using estrogen, progesterone, and HER2 receptors. Multivariate Cox analysis was used to determine the risk of LRR associated with intrinsic subtypes and Ki67 expression, adjusting for known prognostic factors. Results: At a median follow-up of 56 months, 17 patients developed LRR. Five-year LRR-free survival and overall survival in the entire population were 97%, and 94.7%, respectively, with no difference between the PMRT (n=191) and no-PMRT (n=508) subgroups. No constructed subtype was associated with an increased risk of LRR. Ki67 >20% was the only independent prognostic factor associated with increased LRR (hazard ratio, 4.18; 95% CI, 1.11-15.77; P<.0215). However, PMRT was not associated with better locoregional control in patients with proliferative tumors. Conclusions: Ki67 expression but not molecular subtypes are predictors of locoregional recurrence in breast cancer patients with negative lymph nodes after MRM. The benefit of adjuvant RT in patients with proliferative tumors should be further investigated in prospective studies.

  19. Integrated molecular targeting of IGF1R and HER2 surface receptors and destruction of breast cancer cells using single wall carbon nanotubes

    International Nuclear Information System (INIS)

    Shao Ning; Lu Shaoxin; Wickstrom, Eric; Panchapakesan, Balaji

    2007-01-01

    Molecular targeting and photodynamic therapy have shown great potential for selective cancer therapy. We hypothesized that monoclonal antibodies that are specific to the IGF1 receptor and HER2 cell surface antigens could be bound to single wall carbon nanotubes (SWCNT) in order to concentrate SWCNT on breast cancer cells for specific near-infrared phototherapy. SWCNT functionalized with HER2 and IGF1R specific antibodies showed selective attachment to breast cancer cells compared to SWCNT functionalized with non-specific antibodies. After the complexes were attached to specific cancer cells, SWCNT were excited by ∼808 nm infrared photons at ∼800 mW cm -2 for 3 min. Viability after phototherapy was determined by Trypan blue exclusion. Cells incubated with SWCNT/non-specific antibody hybrids were still alive after photo-thermal treatment due to the lack of SWNT binding to the cell membrane. All cancerous cells treated with IGF1R and HER2 specific antibody/SWCNT hybrids and receiving infrared photons showed cell death after the laser excitation. Quantitative analysis demonstrated that all the cells treated with SWCNT/IGF1R and HER2 specific antibody complex were completely destroyed, while more than 80% of the cells with SWCNT/non-specific antibody hybrids remained alive. Following multi-component targeting of IGF1R and HER2 surface receptors, integrated photo-thermal therapy in breast cancer cells led to the complete destruction of cancer cells. Functionalizing SWCNT with antibodies in combination with their intrinsic optical properties can therefore lead to a new class of molecular delivery and cancer therapeutic systems

  20. DARE: a dedicated aerosols retrieval instrument

    NARCIS (Netherlands)

    Court, A.J.; Smorenburg, K.; Courrèges-Lacoste, G.B.; Visser, H.; Leeuw, G. de; Decae, R.

    2004-01-01

    Satellite remote sensing of aerosols is a largely unresolved problem. A dedicated instrument aimed at aerosols would be able to reduce the large uncertainties connected to this kind of remote sensing. TNO is performing a study of a space based instrument for aerosol measurements, together with the

  1. Molecular detection of peripheral blood breast cancer mRNA transcripts as a surrogate biomarker for circulating tumor cells.

    Directory of Open Access Journals (Sweden)

    Adriana Lasa

    Full Text Available Circulating tumor cells (CTCs are becoming a scientifically recognized indicator of primary tumors and/or metastasis. These cells can now be accurately detected and characterized as the result of technological advances. We analyzed the presence of CTCs in the peripheral blood of patients with metastatic breast cancer by real-time reverse-transcription PCR (RT-qPCR using a panel of selected genes. The analysis of a single marker, without an EpCAM based enrichment approach, allowed the positive identification of 35% of the metastatic breast cancer patients. The analysis of five genes (SCGB2, TFF1, TFF3, Muc1, KRT20 performed in all the samples increased the detection to 61%. We describe a sensitive, reproducible and easy to implement approach to characterize CTC in patients with metastasic breast cancer.

  2. Study the Molecular Association between a Deletion Mutation in CHEK2 gene (5395 bp and Breast Cancer

    Directory of Open Access Journals (Sweden)

    Manijeh Jalilvand

    2015-07-01

    Full Text Available Background & Objectives: Breast cancer is the most common cancer among women and the second most common cause of cancer death. Genetic factors play an important role in the development of breast cancer. Among these genetic factors, CHEk2 (checkpoint kinase 2 gene, as a tumor suppressor gene, plays a critical role in DNA repair. Germline mutations in CEHK2 result in the loss of this feature. One of the mutations in CHEK2 gene is a 5395 bp deletion mutation which has been associated with the increasing risk of Breast Cancer in some populations in the world.  In the present study, we investigated the association between a 5395 bp deletion mutation in CHEK2 gene and the risk of Breast Cancer in the women of an Iranian population. Methods: Pathologic information of 38 cases under the age of 45 and 62 cases over the age of 45 referring to surgery ward of Milad Hospital in Tehran were extracted. 100 healthy controls were included in the study as well. After obtaining informed consent, 5 mL whole blood was taken DNA was successfully isolated. Multiplex PCR was used to investigate the association between a 5395bp deletion mutation in CHEK2 gene and increasing risk of Breast Cancer among patients. Results: The 5395bp deletion mutation in CHEK2 gene was not found in any of the participating groups of patients or heathy controls. Conclusion: The present study revealed that there is no significant relation between increasing the risk of Breast Cancer and bearing large deletion mutation in exon 9 and exon 10 of CHECK2 gene.

  3. Clinical utility of scintimammography: From the Anger-camera to new dedicated devices

    Energy Technology Data Exchange (ETDEWEB)

    Schillaci, Orazio [Department of Biopathology and Diagnostic Imaging, University ' Tor Vergata' , Viale G. Mazzini 121, 00195 Rome (Italy)]. E-mail: oschil@tiscali.it; Danieli, Roberta [Department of Biopathology and Diagnostic Imaging, University ' Tor Vergata' , Viale G. Mazzini 121, 00195 Rome (Italy); Romano, Pasquale [Department of Biopathology and Diagnostic Imaging, University ' Tor Vergata' , Viale G. Mazzini 121, 00195 Rome (Italy); Cossu, Elsa [Department of Biopathology and Diagnostic Imaging, University ' Tor Vergata' , Viale G. Mazzini 121, 00195 Rome (Italy); Simonetti, Giovanni [Department of Biopathology and Diagnostic Imaging, University ' Tor Vergata' , Viale G. Mazzini 121, 00195 Rome (Italy)

    2006-12-20

    Scintimammography is a functional imaging technique which uses a radiation detection camera to detect radionuclide tracers in the patient's breasts. Tracers are designed to accumulate in tumours more than in healthy tissue: the most used are Tc-99 m sestamibi and Tc-99 m tetrofosmin. Scintimammography is useful in some clinical indications as an adjunct to mammography: it is recommended for those lesions where additional information is required to reach a definitive diagnosis. Patients with dubious mammograms may benefit from this test, as well as women with dense breasts or with implants. Scintimammography is a valuable diagnostic tool also in patients with locally advanced breast cancer for monitoring and predicting response to neoadjuvant chemotherapy. Nevertheless, using an Anger-camera this technique shows a high sensitivity only for cancers >1 cm. Since other modalities are increasingly employed for the early identification of small abnormalities, the issue of detecting small cancers is critical for the future development and clinical utility of breast imaging with radiopharmaceuticals. The use of high-resolution cameras dedicated for breast imaging is the best option to improve the detection of small cancers: they allow higher flexibility in patient positioning, and the availability of mammography-like projections. Moreover, the detector can be placed directly in contact with the breast allowing a mild compression with reduction of the breast's thickness, thus increasing the target-to-background ratio and the sensitivity. These new devices have the potential of increasing the total number of breast scintigraphies performed thereby enhancing the role of nuclear medicine in breast cancer imaging.

  4. Metastatic Breast Cancer With ESR1 Mutation: Clinical Management Considerations From the Molecular and Precision Medicine (MAP) Tumor Board at Massachusetts General Hospital.

    Science.gov (United States)

    Bardia, Aditya; Iafrate, John A; Sundaresan, Tilak; Younger, Jerry; Nardi, Valentina

    2016-09-01

    : The last decade in oncology has witnessed impressive response rates with targeted therapies, largely because of collaborative efforts at understanding tumor biology and careful patient selection based on molecular fingerprinting of the tumor. Consequently, there has been a push toward routine molecular genotyping of tumors, and large precision medicine-based clinical trials have been launched to match therapy to the molecular alteration seen in a tumor. However, selecting the "right drug" for an individual patient in clinic is a complex decision-making process, including analytical interpretation of the report, consideration of the importance of the molecular alteration in driving growth of the tumor, tumor heterogeneity, the availability of a matched targeted therapy, efficacy and toxicity considerations of the targeted therapy (compared with standard therapy), and reimbursement issues. In this article, we review the key considerations involved in clinical decision making while reviewing a molecular genotyping report. We present the case of a 67-year-old postmenopausal female with metastatic estrogen receptor-positive (ER+) breast cancer, whose tumor progressed on multiple endocrine therapies. Molecular genotyping of the metastatic lesion revealed the presence of an ESR1 mutation (encoding p.Tyr537Asn), which was absent in the primary tumor. The same ESR1 mutation was also detected in circulating tumor DNA (ctDNA) extracted from her blood. The general approach for interpretation of genotyping results, the clinical significance of the specific mutation in the particular cancer, potential strategies to target the pathway, and implications for clinical practice are reviewed in this article. ER+ breast tumors are known to undergo genomic evolution during treatment with the acquisition of new mutations that confer resistance to treatment.ESR1 mutations in the ligand-binding domain of ER can lead to a ligand-independent, constitutively active form of ER and mediate

  5. Intratumor cholesteryl ester accumulation is associated with human breast cancer proliferation and aggressive potential: a molecular and clinicopathological study

    International Nuclear Information System (INIS)

    a Claret, 167 08025, Barcelona (Spain))" data-affiliation=" (Cardiovascular Research Center, CSIC-ICCC, IIB-Sant Pau, Hospital de la Santa Creu i Sant Pau, Sant Antoni Ma Claret, 167 08025, Barcelona (Spain))" >Gonzalo-Calvo, David de; López-Vilaró, Laura; a Claret, 167 08025, Barcelona (Spain))" data-affiliation=" (Cardiovascular Research Center, CSIC-ICCC, IIB-Sant Pau, Hospital de la Santa Creu i Sant Pau, Sant Antoni Ma Claret, 167 08025, Barcelona (Spain))" >Nasarre, Laura; Perez-Olabarria, Maitane; Vázquez, Tania; Escuin, Daniel; a Claret, 167 08025, Barcelona (Spain))" data-affiliation=" (Cardiovascular Research Center, CSIC-ICCC, IIB-Sant Pau, Hospital de la Santa Creu i Sant Pau, Sant Antoni Ma Claret, 167 08025, Barcelona (Spain))" >Badimon, Lina; Barnadas, Agusti; Lerma, Enrique; a Claret, 167 08025, Barcelona (Spain))" data-affiliation=" (Cardiovascular Research Center, CSIC-ICCC, IIB-Sant Pau, Hospital de la Santa Creu i Sant Pau, Sant Antoni Ma Claret, 167 08025, Barcelona (Spain))" >Llorente-Cortés, Vicenta

    2015-01-01

    The metabolic effect of intratumor cholesteryl ester (CE) in breast cancer remains poorly understood. The objective was to analyze the relationship between intratumor CE content and clinicopathological variables in human breast carcinomas. We classified 30 breast carcinoma samples into three subgroups: 10 luminal-A tumors (ER+/PR+/Her2-), 10 Her-2 tumors (ER-/PR-/Her2+), and 10 triple negative (TN) tumors (ER-/PR-/Her2-). We analyzed intratumor neutral CE, free cholesterol (FC) and triglyceride (TG) content by thin layer chromatography after lipid extraction. RNA and protein levels of lipid metabolism and invasion mediators were analyzed by real time PCR and Western blot analysis. Group-wise comparisons, linear regression and logistic regression models showed a close association between CE-rich tumors and higher histologic grade, Ki-67 and tumor necrosis. CE-rich tumors displayed higher mRNA and protein levels of low-density lipoprotein receptor (LDLR) and scavenger receptor class B member 1 (SCARB1). An increased expression of acetyl-Coenzyme A acetyltransferase 1 (ACAT1) in CE-rich tumors was also reported. Intratumor CE accumulation is intimately linked to proliferation and aggressive potential of breast cancer tumors. Our data support the link between intratumor CE content and poor clinical outcome and open the door to new antitumor interventions. The online version of this article (doi:10.1186/s12885-015-1469-5) contains supplementary material, which is available to authorized users

  6. 78 FR 61805 - National Breast Cancer Awareness Month, 2013

    Science.gov (United States)

    2013-10-04

    ... National Breast Cancer Awareness Month, 2013 By the President of the United States of America A... from it. As we observe National Breast Cancer Awareness Month, we salute the women and men who dedicate... October 2013 as National Breast Cancer Awareness Month. I encourage citizens, government agencies, private...

  7. Long-Term Efficacy and Patterns of Failure After Accelerated Partial Breast Irradiation: A Molecular Assay-Based Clonality Evaluation

    International Nuclear Information System (INIS)

    Vicini, Frank A.; Antonucci, J. Vito; Wallace, Michelle R.N.; Gilbert, Samuel; Goldstein, Neal S.; Kestin, Larry; Chen, Peter; Kunzman, Jonathan; Boike, Thomas; Benitez, Pamela; Martinez, Alvaro

    2007-01-01

    Purpose: To determine the long-term efficacy and cosmetic results of accelerated partial breast irradiation (APBI) by reviewing our institution's experience. Methods and Materials: A total of 199 patients with early-stage breast cancer were treated prospectively with adjuvant APBI after lumpectomy using interstitial brachytherapy. All patients had negative margins, 82% had Stage I disease, median tumor size was 1.1 cm, and 12% had positive lymph nodes. The median follow-up for surviving patients was 8.6 years. Fifty-three patients (27%) have been followed for ≥10 years. Results: Six ipsilateral breast tumor recurrences (IBTRs) were observed, for a 5-year and 10-year actuarial rate of 1.6% and 3.8%, respectively. A total of three regional nodal failures were observed, for a 10-year actuarial rate of 1.6%. Five contralateral breast cancers developed, for a 5- and 10-year actuarial rate of 2.2% and 5.2%, respectively. The type of IBTR (clonally related vs. clonally distinct) was analyzed using a polymerase chain reaction-based loss of heterozygosity assay. Eighty-three percent of IBTRs (n = 5) were classified as clonally related. Multiple clinical, pathologic, and treatment-related factors were analyzed for an association with the development of an IBTR, regional nodal failure, or contralateral breast cancer. On multivariate analysis, no variable was associated with any of these events. Cosmetic results were rated as excellent/good in 99% of patients. Conclusions: Long-term results with APBI using interstitial brachytherapy continue to demonstrate excellent long-term local and regional control rates and cosmetic results. According to a polymerase chain reaction-based loss of heterozygosity assay, 83% of recurrences were classified as clonally related

  8. The AMFEC: a tool for dedications

    International Nuclear Information System (INIS)

    Pastor Escobar, H.; Gomar Vidal, J.

    2014-01-01

    The process of dedication, consists of a series of activities intended to ensure that a component of commercial grade can be used in applications related with the Security at nuclear facilities. However, in one of the steps of essential dedication, is often the problem defined with certain accuracy the most relevant characteristics or critical acceptance of the component characteristics, which through its verification, give by valid the commercial component for security-related use. Due to lack of information, they can sometimes not be identified clearly, and therefore it is necessary to resort to some alternative method that will allow us to define them, the AMFEC (analysis of failure modes, effects and criticality. (Author)

  9. Dedication of Fermilab's LHC Remote Operations Center

    CERN Multimedia

    Claudia Marcelloni

    2007-01-01

    Fermilab's Remote Operations Center will be dedicated simultaneously at Fermilab in the U.S. and from CMS (Point 5) in Cessy, France. Speakers will include: from the U.S. DOE Undersecretary for Science Raymond Orbach and Fermilab Director Pier Oddone (U.S.); and from CERN Director General Robert Aymar, CMS Spokesperson Jim Virdee, LHC Project Leader Lyn Evans and US CMS Project Manager Joel Butler.

  10. Dedicating Fermilab's Collider

    International Nuclear Information System (INIS)

    Anon.

    1986-01-01

    It was a bold move to have a fullscale dedication ceremony for the new proton-antiproton Collider at the Fermilab Tevatron on 13 October, two days before the first collisions were seen. However the particles dutifully behaved as required, and over the following weekend the Collider delivered its goods at a total energy of 1600 GeV, significantly boosting the world record for laboratory collisions

  11. Breast Cancer Tissue Repository

    National Research Council Canada - National Science Library

    Iglehart, J

    1997-01-01

    The Breast Tissue Repository at Duke enters its fourth year of finding. The purpose of the Repository at Duke is to provide substantial quantities of frozen tissue for explorative molecular studies...

  12. Highly sensitive detection of ESR1 mutations in cell-free DNA from patients with metastatic breast cancer using molecular barcode sequencing.

    Science.gov (United States)

    Masunaga, Nanae; Kagara, Naofumi; Motooka, Daisuke; Nakamura, Shota; Miyake, Tomohiro; Tanei, Tomonori; Naoi, Yasuto; Shimoda, Masafumi; Shimazu, Kenzo; Kim, Seung Jin; Noguchi, Shinzaburo

    2018-01-01

    We aimed to develop a highly sensitive method to detect ESR1 mutations in cell-free DNA (cfDNA) using next-generation sequencing with molecular barcode (MB-NGS) targeting the hotspot segment (c.1600-1713). The sensitivity of MB-NGS was tested using serially diluted ESR1 mutant DNA and then cfDNA samples from 34 patients with metastatic breast cancer were analyzed with MB-NGS. The results of MB-NGS were validated in comparison with conventional NGS and droplet digital PCR (ddPCR). MB-NGS showed a higher sensitivity (0.1%) than NGS without barcode (1%) by reducing background errors. Of the cfDNA samples from 34 patients with metastatic breast cancer, NGS without barcode revealed seven mutations in six patients (17.6%) and MB-NGS revealed six additional mutations including three mutations not reported in the COSMIC database of breast cancer, resulting in total 13 ESR1 mutations in ten patients (29.4%). Regarding the three hotspot mutations, all the patients with mutations detected by MB-NGS had identical mutations detected by droplet digital PCR (ddPCR), and mutant allele frequency correlated very well between both (r = 0.850, p < 0.01). Moreover, all the patients without these mutations by MB-NGS were found to have no mutations by ddPCR. In conclusion, MB-NGS could successfully detect ESR1 mutations in cfDNA with a higher sensitivity of 0.1% than conventional NGS and was considered as clinically useful as ddPCR.

  13. Magnetic resonance imaging in breast cancer treated with neoadjuvant chemotherapy: radiologic-pathologic correlation of the response and disease-free survival depending on molecular subtype.

    Science.gov (United States)

    Cruz Ciria, S; Jiménez Aragón, F; García Mur, C; Esteban Cuesta, H; Gros Bañeres, B

    2014-01-01

    To evaluate the radiologic and pathologic responses to neoadjuvant chemotherapy and their correlation in the molecular subtypes of breast cancer and to analyze their impact in disease-free survival. We included 205 patients with breast cancer treated with neoadjuvant chemotherapy. We evaluated the radiologic response by comparing MRI images acquired before and after chemotherapy. The pathologic response was classified on the Miller and Payne scale. For each subtype (HER2+, TN, luminal A, luminal B HER2-, and luminal B HER2+), we used the χ(2) test, Student's t-test, ANOVA, and Kendall's Tau-b to evaluate the radiologic response and the pathologic response, the radiologic-pathologic correlation, and the disease-free survival. The subtypes HER2+ (62.1%) and TN (45.2%) had higher rates of complete radiologic response. The pathologic response was 65.5% in the HER2+ subtype, 38.1% in the TN subtype, 2.6% in the luminal A subtype, 8.2% in the luminal B HER2- subtype, and 31% in the luminal B HER2+ subtype. The rate of radiologic-pathologic correlation was significant in all subtypes, higher in TN and HER2 (Tau-b coefficients 0.805 and 0.717, respectively). Disease-free survival was higher in HER2+ (91.9±3.3 months) and lower in TN (69.5±6.3 months), with significant differences between the cases with poor and good radiologic responses (P=.040). Survival was greater in cases with good radiologic response, except in cases with luminal A subtype. MRI can be a useful tool that provides information about the evolution of breast cancer treated with neoadjuvant chemotherapy, which varies with the immunohistochemical subtype. Copyright © 2012 SERAM. Published by Elsevier Espana. All rights reserved.

  14. Integrating molecular mechanisms and clinical evidence in the management of trastuzumab resistant or refractory HER-2⁺ metastatic breast cancer.

    Science.gov (United States)

    Wong, Hilda; Leung, Roland; Kwong, Ava; Chiu, Joanne; Liang, Raymond; Swanton, Charles; Yau, Thomas

    2011-01-01

    Human epidermal growth factor receptor (HER)-2(+) breast cancer is a distinct molecular and clinical entity, the prognosis of which is improved by trastuzumab. However, primary resistance to trastuzumab is observed in >50% of patients with HER-2(+) advanced breast cancer, and the majority of patients who initially respond to treatment eventually develop disease progression. To facilitate crosstrial comparisons and the understanding of resistance mechanisms, we propose a unifying definition of trastuzumab resistance as progression at first radiological reassessment at 8-12 weeks or within 3 months after first-line trastuzumab in the metastatic setting or new recurrences diagnosed during or within 12 months after adjuvant trastuzumab. In contrast, we define trastuzumab-refractory breast cancer as disease progression after two or more lines of trastuzumab-containing regimens that initially achieved disease response or stabilization at first radiological assessment. We review mechanisms of trastuzumab resistance mediated by p95HER-2 overexpression, phosphoinositide 3-kinase pathway activation, and signaling pathway activation driven by HER-3, epidermal growth factor receptor, and insulin-like growth factor 1 receptor. We distinguish in vitro from in vivo evidence, highlighting that most data describing trastuzumab resistance are derived from preclinical studies or small retrospective patient cohorts, and discuss targeted therapeutic approaches to overcome resistance. Prospective analysis through clinical trials with robust tissue collection procedures, prior to and following acquisition of resistance, integrated with next-generation tumor genome sequencing technologies, is identified as a priority area for development. The identification of predictive biomarkers is of paramount importance to optimize health economic costs and enhance stratification of anti-HER-2 targeted therapies.

  15. Effects on image quality of a 2D antiscatter grid in x-ray digital breast tomosynthesis: Initial experience using the dual modality (x-ray and molecular) breast tomosynthesis scanner

    Energy Technology Data Exchange (ETDEWEB)

    Patel, Tushita, E-mail: tp3rn@virginia.edu [Department of Physics, University of Virginia, Charlottesville, Virginia 22904 (United States); Peppard, Heather [Department of Radiology and Medical Imaging, University of Virginia, Charlottesville, Virginia 22908 (United States); Williams, Mark B. [Department of Physics, University of Virginia, Charlottesville, Virginia 22904 (United States); Department of Radiology and Medical Imaging, University of Virginia, Charlottesville, Virginia 22908 (United States); Department of Biomedical Engineering, University of Virginia, Charlottesville, Virginia 22908 (United States)

    2016-04-15

    Purpose: Radiation scattered from the breast in digital breast tomosynthesis (DBT) causes image degradation, including loss of contrast between cancerous and background tissue. Unlike in 2-dimensional (2D) mammography, an antiscatter grid cannot readily be used in DBT because changing alignment between the tube and detector during the scan would result in unacceptable loss of primary radiation. However, in the dual modality breast tomosynthesis (DMT) scanner, which combines DBT and molecular breast tomosynthesis, the tube and detector rotate around a common axis, thereby maintaining a fixed tube-detector alignment. This C-arm geometry raises the possibility of using a 2D (cellular) focused antiscatter grid. The purpose of this study is to assess change in image quality when using an antiscatter grid in the DBT portion of a DMT scan under conditions of fixed radiation dose. Methods: Two 2D focused prototype grids with 80 cm focal length were tested, one stack-laminated from copper (Cu) and one cast from a tungsten-polymer (W-poly). They were reciprocated using a motion scheme designed to maximize transmission of primary x-ray photons. Grid-in and grid-out scatter-to-primary ratios (SPRs) were measured for rectangular blocks of material simulating 30%, 50%, and 70% glandular tissue compositions. For assessment of changes in image quality through the addition of a grid, the Computerized Imaging Reference Systems, Inc., phantom Model 011A containing a set of 1 cm thick blocks simulating a range of glandular/adipose ratios from 0/100 to 100/0 was used. To simulate 6.5 and 8.5 cm thick compressed breasts, 1 cm thick slices of PMMA were added to the Model 011A phantom. DBT images were obtained with and without the grid, with exposure parameters fixed for a given compressed thickness. Signal-difference-to-noise ratios (SDNRs), contrast, and voxel value-based attenuation coefficients (μ) were measured for all blocks from reconstructed phantom images. Results: For 4, 6, and

  16. Development of RNA aptamers as molecular probes for HER2+ breast cancer study using cell-SELEX

    Directory of Open Access Journals (Sweden)

    Seyedeh Alia Moosavian

    2015-06-01

    Full Text Available Objective(s: Development of molecules that specifically recognize cancer cells is one of the major areas in cancer research. Human epidermal growth factor receptor 2 (HER2 is specifically expressed on the surface of breast cancer cells. HER2 is associated with an aggressive phenotype and poor prognosis. In this study we aimed to isolate RNA aptamers that specifically bind to HER2 overexpressing TUBO cell line. Materials and Methods: Panel of aptamers was selected using cell-based systematic evolution of ligands by exponential enrichment (cell-SELEX. Results: Binding studies showed that selected aptamers can identify TUBO cell line with high affinity and selectivity. Our preliminary investigation of the target of aptamers suggested that aptamers bind with HER2 proteins on the surface of TUBO cells. Conclusion: We believe the selected aptamers could be useful ligands for targeted breast cancer therapy.

  17. Molecular analysis of the eighteen most frequent mutations in the BRCA1 gene in 63 Chilean breast cancer families

    Directory of Open Access Journals (Sweden)

    LILIAN JARA

    2004-01-01

    Full Text Available BRCA1 gene mutations account for nearly all families with multiple cases of both early onset breast and/or ovarian cancer and about 30% of hereditary breast cancer. Although to date more than 1,237 distinct mutations, polymorphisms, and variants have been described, several mutations have been found to be recurrent in this gene. We have analyzed 63 Chilean breast/ovarian cancer families for eighteen frequent BRCA1 mutations. The analysis of the five exons and two introns in which these mutations are located was made using mismatch PCR assay, ASO hybridization assay, restriction fragment analysis, allele specific PCR assay and direct sequentiation techniques. Two BRCA1 mutations (185delAG and C61G and one variant of unknown significance (E1250K were found in four of these families. Also, a new mutation (4185delCAAG and one previously described polymorphism (E1038G were found in two other families. The 185delAG was found in a 3.17 % of the families and the others were present only in one of the families of this cohort. Therefore these mutations are not prominent in the Chilean population. The variant of unknown significance and the polymorphism detected could represent a founder effect of Spanish origin

  18. Breast Pain

    Science.gov (United States)

    ... result in the development of breast cysts. Breast trauma, prior breast surgery or other factors localized to the breast can lead to breast pain. Breast pain may also start outside the breast — in the chest wall, muscles, joints or heart, for example — and ...

  19. Quantum mechanical/molecular mechanical and docking study of the novel analogues based on hybridization of common pharmacophores as potential anti-breast cancer agents.

    Science.gov (United States)

    Asadi, Parvin; Khodarahmi, Ghadamali; Farrokhpour, Hossein; Hassanzadeh, Farshid; Saghaei, Lotfollah

    2017-06-01

    In an attempt to identify some new potential leads as anti-breast cancer agents, novel hybrid compounds were designed by molecular hybridization approach. These derivatives were structurally derived from hybrid benzofuran-imidazole and quinazolinone derivatives, which had shown good cytotoxicity against the breast cancer cell line (MCF-7). Since aromatase enzyme (CYP19) is highly expressed in the MCF-7 cell line, the binding of these novel hybrid compounds to aromatase was investigated using the docking method. In this study, due to the positive charge on the imidazole ring of the designed ligands and also, the presence of heme iron in the active site of the enzyme, it was decided to optimize the ligand inside the protein to obtain more realistic atomic charges for it. Quantum mechanical/molecular mechanical (QM/MM) method was used to obtain more accurate atomic charges of ligand for docking calculations by considering the polarization effects of CYP19 on ligands. It was observed that the refitted charge improved the binding energy of the docked compounds. Also, the results showed that these novel hybrid compounds were adopted properly within the aromatase binding site, thereby suggesting that they could be potential inhibitors of aromatase. The main binding modes in these complexes were through hydrophobic and H bond interactions showing agreement with the basic physicochemical features of known anti aromatase compounds. Finally, the complex structures obtained from the docking study were used for single point QM/MM calculations to obtain more accurate electronic interaction energy, considering the electronic polarization of the ligand by its protein environment.

  20. A PET imaging system dedicated to mammography

    CERN Document Server

    Varela, J

    2007-01-01

    The imaging system Clear-PEM for positron emission mammography, under development within the framework of the Crystal Clear Collaboration at CERN, is presented. The detector is based on pixelized LYSO crystals optically coupled to avalanche photodiodes (APD) and readout by a fast low-noise electronic system. A dedicated digital trigger and data acquisition system is used for on-line selection of coincidence events with high efficiency, large bandwidth and negligible dead-time. The detector module performance was characterized in detail.

  1. Ford F250 Dedicated CNG Pickup

    International Nuclear Information System (INIS)

    Eudy, Leslie

    1999-01-01

    The U.S. Department of Energy (DOE) is encouraging the use of alternative fuels and alternative fuel vehicles (AFVs). To support this activity, DOE has directed the National Renewable Energy Laboratory (NREL) to conduct projects to evaluate the performance and acceptability of light-duty AFVs. In this study, we tested a pair of 1998 Ford F-250 pickups: one dedicated compressed natural gas (CNG) model and a gasoline model as closely matched as possible. Each vehicle was run through a series of tests to evaluate acceleration, fuel economy, braking, and cold-start capabilities, as well as more subjective performance indicators such as handling, climate control, and noise

  2. Snail-induced epithelial-to-mesenchymal transition of MCF-7 breast cancer cells: systems analysis of molecular changes and their effect on radiation and drug sensitivity

    International Nuclear Information System (INIS)

    Mezencev, Roman; Matyunina, Lilya V.; Jabbari, Neda; McDonald, John F.

    2016-01-01

    Epithelial-to-mesenchymal transition (EMT) has been associated with the acquisition of metastatic potential and the resistance of cancer cells to therapeutic treatments. MCF-7 breast cancer cells engineered to constitutively express the zinc-finger transcriptional repressor gene Snail (MCF-7-Snail cells) have been previously shown to display morphological and molecular changes characteristic of EMT. We report here the results of a comprehensive systems level molecular analysis of changes in global patterns of gene expression and levels of glutathione and reactive oxygen species (ROS) in MCF-7-Snail cells and the consequence of these changes on the sensitivity of cells to radiation treatment and therapeutic drugs. Snail-induced changes in global patterns of gene expression were identified by microarray profiling using the Affymetrix platform (U133 Plus 2.0). The resulting data were processed and analyzed by a variety of system level analytical methods. Levels of ROS and glutathione (GSH) were determined by fluorescent and luminescence assays, and nuclear levels of NF-κB protein were determined by an ELISA based method. The sensitivity of cells to ionizing radiation and anticancer drugs was determined using a resazurin-based cell cytotoxicity assay. Constitutive ectopic expression of Snail in epithelial-like, luminal A-type MCF-7 cells induced significant changes in the expression of >7600 genes including gene and miRNA regulators of EMT. Mesenchymal-like MCF-7-Snail cells acquired molecular profiles characteristic of triple-negative, claudin-low breast cancer cells, and displayed increased sensitivity to radiation treatment, and increased, decreased or no change in sensitivity to a variety of anticancer drugs. Elevated ROS levels in MCF-7-Snail cells were unexpectedly not positively correlated with NF-κB activity. Ectopic expression of Snail in MCF-7 cells resulted in morphological and molecular changes previously associated with EMT. The results underscore the

  3. Selective molecularly imprinted polymer combined with restricted access material for in-tube SPME/UHPLC-MS/MS of parabens in breast milk samples

    International Nuclear Information System (INIS)

    Souza, Israel D.; Melo, Lidervan P.; Jardim, Isabel C.S.F.; Monteiro, Juliana C.S.; Nakano, Ana Marcia S.; Queiroz, Maria Eugênia C.

    2016-01-01

    A new molecularly imprinted polymer modified with restricted access material (a hydrophilic external layer), (MIP-RAM) was synthesized via polymerization in situ in an open fused silica capillary. This stationary phase was used as sorbent for in-tube solid phase microextraction (in-tube SPME) to determine parabens in breast milk samples by ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Scanning electron micrographs (SEM) illustrate MIP surface modification after glycerol dimethacrylate (hydrophilic monomer) incorporation. The interaction between parabens and MIP-RAM was investigated by Fourier-transform infrared (FTIR) spectroscopy. The Scatchard plot for MIP-RAM presented two linear parts with different slopes, illustrating binding sites with high- and low-affinity. Endogenous compounds exclusion from the MIP-RAM capillary was demonstrated by in-tube SPME/LC-UV assays carried out with blank milk samples. The in-tube SPME/UHPLC-MS/MS method presented linear range from 10 ng mL"−"1 (LLOQ) to 400 ng mL"−"1 with coefficients of determination higher than 0.99, inter-assay precision with coefficient of variation (CV) values ranging from 2 to 15%, and inter-assay accuracy with relative standard deviation (RSD) values ranging from −1% to 19%. Analytical validation parameters attested that in-tube SPME/UHPLC-MS/MS is an appropriate method to determine parabens in human milk samples to assess human exposure to these compounds. Analysis of breast milk samples from lactating women demonstrated that the proposed method is effective. - Highlights: • Molecularly imprinted polymer modified with a hydrophilic external layer (RAM-MIP) was synthesized in a silica capillary. • RAM-MIP capillary, used as sorbent for in-tube SPME, established specific interaction with parabens present in milk samples. • The matrix components that interacted only with the hydrophilic external layer (non-adsorptive network) were excluded. • The

  4. Selective molecularly imprinted polymer combined with restricted access material for in-tube SPME/UHPLC-MS/MS of parabens in breast milk samples

    Energy Technology Data Exchange (ETDEWEB)

    Souza, Israel D.; Melo, Lidervan P. [Departamento de Química, Faculdade de Filosofia Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Jardim, Isabel C.S.F. [Instituto de Química, Universidade Estadual de Campinas, Campinas, SP (Brazil); Monteiro, Juliana C.S.; Nakano, Ana Marcia S. [Escola de Enfermagem de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Queiroz, Maria Eugênia C., E-mail: mariaeqn@ffclrp.usp.br [Departamento de Química, Faculdade de Filosofia Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil)

    2016-08-17

    A new molecularly imprinted polymer modified with restricted access material (a hydrophilic external layer), (MIP-RAM) was synthesized via polymerization in situ in an open fused silica capillary. This stationary phase was used as sorbent for in-tube solid phase microextraction (in-tube SPME) to determine parabens in breast milk samples by ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Scanning electron micrographs (SEM) illustrate MIP surface modification after glycerol dimethacrylate (hydrophilic monomer) incorporation. The interaction between parabens and MIP-RAM was investigated by Fourier-transform infrared (FTIR) spectroscopy. The Scatchard plot for MIP-RAM presented two linear parts with different slopes, illustrating binding sites with high- and low-affinity. Endogenous compounds exclusion from the MIP-RAM capillary was demonstrated by in-tube SPME/LC-UV assays carried out with blank milk samples. The in-tube SPME/UHPLC-MS/MS method presented linear range from 10 ng mL{sup −1} (LLOQ) to 400 ng mL{sup −1} with coefficients of determination higher than 0.99, inter-assay precision with coefficient of variation (CV) values ranging from 2 to 15%, and inter-assay accuracy with relative standard deviation (RSD) values ranging from −1% to 19%. Analytical validation parameters attested that in-tube SPME/UHPLC-MS/MS is an appropriate method to determine parabens in human milk samples to assess human exposure to these compounds. Analysis of breast milk samples from lactating women demonstrated that the proposed method is effective. - Highlights: • Molecularly imprinted polymer modified with a hydrophilic external layer (RAM-MIP) was synthesized in a silica capillary. • RAM-MIP capillary, used as sorbent for in-tube SPME, established specific interaction with parabens present in milk samples. • The matrix components that interacted only with the hydrophilic external layer (non-adsorptive network) were excluded.

  5. Genomic features of lobular breast carcinoma

    Science.gov (United States)

    Investigators with The Cancer Genome Atlas (TCGA) Research Network have identified molecular characteristics of a type of breast cancer, invasive lobular carcinoma (ILC), that distinguishes it from invasive ductal carcinoma (IDC), the most common invasive breast cancer subtype.

  6. Dedicated Filter for Robust Occupancy Grid Mapping

    Directory of Open Access Journals (Sweden)

    KS Nagla

    2015-03-01

    Full Text Available Sensor based perception of the environment is an emerging area of the mobile robot research where sensors play a pivotal role. For autonomous mobile robots, the fundamental requirement is the convergent of the range information in to high level internal representation. Internal representation in the form of occupancy grid is commonly used in autonomous mobile robots due to its various advantages. There are several sensors such as vision sensor, laser rage finder, and ultrasonic and infrared sensors etc. play roles in mapping. However the sensor information failure, sensor inaccuracies, noise, and slow response are the major causes of an error in the mapping. To improve the reliability of the mobile robot mapping multisensory data fusion is considered as an optimal solution. This paper presents a novel architecture of sensor fusion frame work in which a dedicated filter (DF is proposed to increase the robustness of the occupancy grid for indoor environment. The technique has been experimentally verified for different indoor test environments. The proposed configuration shows improvement in the occupancy grid with the implementation of dedicated filters.

  7. Dedicated low-field MRI in mice

    International Nuclear Information System (INIS)

    Choquet, P; Breton, E; Goetz, C; Constantinesco, A; Marin, C

    2009-01-01

    The rationale of this work is to point out the relevance of in vivo MR images of mice obtained using a dedicated low-field system. For this purpose a small 0.1 T water-cooled electro-magnet and solenoidal radio frequency (RF) transmit-receive coils were used. All MR images were acquired in three-dimensional (3D) mode. An isolation cell was designed allowing easy placement of the RF coils and simple delivery of gaseous anesthesia as well as warming of the animal. Images with and without contrast agent were obtained in total acquisition times on the order of half an hour to four hours on normal mice as well as on animals bearing tumors. Typical in plane pixel dimensions range from 200 x 200 to 500 x 500 μm 2 with slice thicknesses ranging between 0.65 and 1.50 mm. This work shows that, besides light installation and low cost, dedicated low-field MR systems are suitable for small rodents imaging, opening this technique even to small research units.

  8. Dedicated low-field MRI in mice

    Science.gov (United States)

    Choquet, P.; Breton, E.; Goetz, C.; Marin, C.; Constantinesco, A.

    2009-09-01

    The rationale of this work is to point out the relevance of in vivo MR images of mice obtained using a dedicated low-field system. For this purpose a small 0.1 T water-cooled electro-magnet and solenoidal radio frequency (RF) transmit-receive coils were used. All MR images were acquired in three-dimensional (3D) mode. An isolation cell was designed allowing easy placement of the RF coils and simple delivery of gaseous anesthesia as well as warming of the animal. Images with and without contrast agent were obtained in total acquisition times on the order of half an hour to four hours on normal mice as well as on animals bearing tumors. Typical in plane pixel dimensions range from 200 × 200 to 500 × 500 µm2 with slice thicknesses ranging between 0.65 and 1.50 mm. This work shows that, besides light installation and low cost, dedicated low-field MR systems are suitable for small rodents imaging, opening this technique even to small research units.

  9. The molecular cues for the biological effects of ionizing radiation dose and post-irradiation time on human breast cancer SKBR3 cell line: A Raman spectroscopy study.

    Science.gov (United States)

    Jafarzadeh, Naser; Mani-Varnosfaderani, Ahmad; Gilany, Kambiz; Eynali, Samira; Ghaznavi, Habib; Shakeri-Zadeh, Ali

    2018-03-01

    Radiotherapy is one of the main modalities of cancer treatment. The utility of Raman spectroscopy (RS) for detecting the distinct radiobiological responses in human cancer cells is currently under investigation. RS holds great promises to provide good opportunities for personalizing radiotherapy treatments. Here, we report the effects of the radiation dose and post-irradiation time on the molecular changes in the human breast cancer SKBR3 cells, using RS. The SKBR3 cells were irradiated by gamma radiation with different doses of 0, 1, 2, 4, and 6 Gy. The Raman signals were acquired 24 and 48 h after the gamma radiation. The collected Raman spectra were analyzed by different statistical methods such as principal component analysis, linear discriminant analysis, and genetic algorithm. A thorough analysis of the obtained Raman signals revealed that 2 Gy of gamma radiation induces remarkable molecular and structural changes in the SKBR3 cells. We found that the wavenumbers in the range of 1000-1400 cm -1 in Raman spectra are selective for discriminating between the effects of the different doses of irradiation. The results also revealed that longer post-irradiation time leads to the relaxation of the cells to their initial state. The molecular changes that occurred in the 2Gy samples were mostly reversible. On the other hand, the exposure to doses higher than 4Gy induced serious irreversible changes, mainly seen in 2700-2800 cm -1 in Raman spectra. The classification models developed in this study would help to predict the radiation-based molecular changes induced in the cancer cells by only using RS. Also, this designed framework may facilitate the process of biodosimetry. Copyright © 2018 Elsevier B.V. All rights reserved.

  10. Heterogeneity of Mesenchymal Markers Expression—Molecular Profiles of Cancer Cells Disseminated by Lymphatic and Hematogenous Routes in Breast Cancer

    International Nuclear Information System (INIS)

    Markiewicz, Aleksandra; Książkiewicz, Magdalena; Seroczyńska, Barbara; Skokowski, Jarosław; Szade, Jolanta; Wełnicka-Jaśkiewicz, Marzena; Zaczek, Anna J.

    2013-01-01

    Breast cancers can metastasize via hematogenous and lymphatic routes, however in some patients only one type of metastases are detected, suggesting a certain proclivity in metastatic patterns. Since epithelial-mesenchymal transition (EMT) plays an important role in cancer dissemination it would be worthwhile to find if a specific profile of EMT gene expression exists that is related to either lymphatic or hematogenous dissemination. Our study aimed at evaluating gene expression profile of EMT-related markers in primary tumors (PT) and correlated them with the pattern of metastatic spread. From 99 early breast cancer patients peripheral blood samples (N = 99), matched PT (N = 47) and lymph node metastases (LNM; N = 22) were collected. Expression of TWIST1, SNAI1, SNAI2 and VIM was analyzed in those samples. Additionally expression of CK19, MGB1 and HER2 was measured in CTCs-enriched blood fractions (CTCs-EBF). Results were correlated with each other and with clinico-pathological data of the patients. Results show that the mesenchymal phenotype of CTCs-EBF correlated with poor clinico-pathological characteristics of the patients. Additionally, PT shared more similarities with LNM than with CTCs-EBF. Nevertheless, LNM showed increased expression of EMT-related markers than PT; and EMT itself in PT did not seem to be necessary for lymphatic dissemination

  11. Commercial Grade Item (CGI) dedication - on complex electronic equipment

    International Nuclear Information System (INIS)

    Sohn, Kwang Young; Kim, Joong Han; Koo, In Soo; Lee, Sang Yong

    2008-01-01

    In future more complicated IT-based hardware and software is supposed to used in the safety-grade systems in nuclear power plants. Also there are the efforts to establish the criteria for CGI dedications in NRC and CEC dedication in other standard organizations. The highly complicated components, i.e. CEC should be dedication plans. Thus work to be done in later is to prepare the strategies, plans, guide and procedures that is more specific for CEC dedication

  12. A dedicated fund supports technological innovation

    CERN Document Server

    Katarina Anthony

    2010-01-01

    The Knowledge and Technology Transfer (KTT) Group is calling on CERN Departments to take their technology out of the confines of the laboratory and make it ready for dissemination. For the first time, projects can apply for financial support from the newly established KTT Fund.   Scientific inquiry can lead to unexpected developments for society when researchers apply their expertise for public use. CERN actively encourages this transfer of knowledge and technology and, for the first time, has created a dedicated fund to provide financial support to projects aiming at disseminating their technologies to external audiences. CERN’s technology transfer schemes were formalised in the recent Policy on the Management of Intellectual Property in Technology Transfer, approved in March. Revenues generated by commercial exploitation will be distributed between the members of the team that developed the technology, their Department, and the KTT Fund for reinvestment in further KTT projects. &qu...

  13. Optical Design Using Small Dedicated Computers

    Science.gov (United States)

    Sinclair, Douglas C.

    1980-09-01

    Since the time of the 1975 International Lens Design Conference, we have developed a series of optical design programs for Hewlett-Packard desktop computers. The latest programs in the series, OSLO-25G and OSLO-45G, have most of the capabilities of general-purpose optical design programs, including optimization based on exact ray-trace data. The computational techniques used in the programs are similar to ones used in other programs, but the creative environment experienced by a designer working directly with these small dedicated systems is typically much different from that obtained with shared-computer systems. Some of the differences are due to the psychological factors associated with using a system having zero running cost, while others are due to the design of the program, which emphasizes graphical output and ease of use, as opposed to computational speed.

  14. 47 CFR 69.125 - Dedicated signalling transport.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 3 2010-10-01 2010-10-01 false Dedicated signalling transport. 69.125 Section... (CONTINUED) ACCESS CHARGES Computation of Charges § 69.125 Dedicated signalling transport. (a) Dedicated signalling transport shall consist of two elements, a signalling link charge and a signalling transfer point...

  15. Human Leukocyte Antigen (HLA) Genotype as a Contributor to Racial/Ethnic Differences in Breast Cancer: A Population-Based, Molecular Epidemiologic Study

    National Research Council Canada - National Science Library

    Glaser, Sally L

    2005-01-01

    ...; whether HLA genotype is related to breast cancer overall; whether associations and prevalence of associated HLA genotypes vary by race/ethnicity, and how much such differences explain racial/ethnic differences in breast cancer incidence...

  16. PAM50 Breast Cancer Subtyping by RT-qPCR and Concordance with Standard Clinical Molecular Markers

    Directory of Open Access Journals (Sweden)

    Bastien Roy RL

    2012-10-01

    Full Text Available Abstract Background Many methodologies have been used in research to identify the “intrinsic” subtypes of breast cancer commonly known as Luminal A, Luminal B, HER2-Enriched (HER2-E and Basal-like. The PAM50 gene set is often used for gene expression-based subtyping; however, surrogate subtyping using panels of immunohistochemical (IHC markers are still widely used clinically. Discrepancies between these methods may lead to different treatment decisions. Methods We used the PAM50 RT-qPCR assay to expression profile 814 tumors from the GEICAM/9906 phase III clinical trial that enrolled women with locally advanced primary invasive breast cancer. All samples were scored at a single site by IHC for estrogen receptor (ER, progesterone receptor (PR, and Her2/neu (HER2 protein expression. Equivocal HER2 cases were confirmed by chromogenic in situ hybridization (CISH. Single gene scores by IHC/CISH were compared with RT-qPCR continuous gene expression values and “intrinsic” subtype assignment by the PAM50. High, medium, and low expression for ESR1, PGR, ERBB2, and proliferation were selected using quartile cut-points from the continuous RT-qPCR data across the PAM50 subtype assignments. Results ESR1, PGR, and ERBB2 gene expression had high agreement with established binary IHC cut-points (area under the curve (AUC ≥ 0.9. Estrogen receptor positivity by IHC was strongly associated with Luminal (A and B subtypes (92%, but only 75% of ER negative tumors were classified into the HER2-E and Basal-like subtypes. Luminal A tumors more frequently expressed PR than Luminal B (94% vs 74% and Luminal A tumors were less likely to have high proliferation (11% vs 77%. Seventy-seven percent (30/39 of ER-/HER2+ tumors by IHC were classified as the HER2-E subtype. Triple negative tumors were mainly comprised of Basal-like (57% and HER2-E (30% subtypes. Single gene scoring for ESR1, PGR, and ERBB2 was more prognostic than the corresponding IHC markers as

  17. Multifunctional dendrimer-based nanoparticles for in vivo MR/CT dual-modal molecular imaging of breast cancer

    Directory of Open Access Journals (Sweden)

    Li K

    2013-07-01

    Full Text Available Kangan Li,1,4,5,* Shihui Wen,2,* Andrew C Larson,4,5 Mingwu Shen,2 Zhuoli Zhang,4,5 Qian Chen,3 Xiangyang Shi,2,3 Guixiang Zhang1 1Department of Radiology, Shanghai First People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China; 2College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai, People’s Republic of China; 3State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, Donghua University, Shanghai, People’s Republic of China; 4Departments of Radiology and Biomedical Engineering, Northwestern University, Chicago, IL, USA; 5Robert H Lurie Comprehensive Cancer Center, Chicago, IL, USA *These authors contributed equally to this work Abstract: Development of dual-mode or multi-mode imaging contrast agents is important for accurate and self-confirmatory diagnosis of cancer. We report a new multifunctional, dendrimer-based gold nanoparticle (AuNP as a dual-modality contrast agent for magnetic resonance (MR/computed tomography (CT imaging of breast cancer cells in vitro and in vivo. In this study, amine-terminated generation 5 poly(amidoamine dendrimers modified with gadolinium chelate (DOTA-NHS and polyethylene glycol monomethyl ether were used as templates to synthesize AuNPs, followed by Gd(III chelation and acetylation of the remaining dendrimer terminal amine groups; multifunctional dendrimer-entrapped AuNPs (Gd-Au DENPs were formed. The formed Gd-Au DENPs were used for both in vitro and in vivo MR/CT imaging of human MCF-7 cancer cells. Both MR and CT images demonstrate that MCF-7 cells and the xenograft tumor model can be effectively imaged. The Gd-Au DENPs uptake, mainly in the cell cytoplasm, was confirmed by transmission electron microscopy. The cell cytotoxicity assay, cell morphology observation, and flow cytometry show that the developed Gd-Au DENPs have good biocompatibility in the given concentration range. Our results

  18. Selective molecularly imprinted polymer combined with restricted access material for in-tube SPME/UHPLC-MS/MS of parabens in breast milk samples.

    Science.gov (United States)

    Souza, Israel D; Melo, Lidervan P; Jardim, Isabel C S F; Monteiro, Juliana C S; Nakano, Ana Marcia S; Queiroz, Maria Eugênia C

    2016-08-17

    A new molecularly imprinted polymer modified with restricted access material (a hydrophilic external layer), (MIP-RAM) was synthesized via polymerization in situ in an open fused silica capillary. This stationary phase was used as sorbent for in-tube solid phase microextraction (in-tube SPME) to determine parabens in breast milk samples by ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Scanning electron micrographs (SEM) illustrate MIP surface modification after glycerol dimethacrylate (hydrophilic monomer) incorporation. The interaction between parabens and MIP-RAM was investigated by Fourier-transform infrared (FTIR) spectroscopy. The Scatchard plot for MIP-RAM presented two linear parts with different slopes, illustrating binding sites with high- and low-affinity. Endogenous compounds exclusion from the MIP-RAM capillary was demonstrated by in-tube SPME/LC-UV assays carried out with blank milk samples. The in-tube SPME/UHPLC-MS/MS method presented linear range from 10 ng mL(-1) (LLOQ) to 400 ng mL(-1) with coefficients of determination higher than 0.99, inter-assay precision with coefficient of variation (CV) values ranging from 2 to 15%, and inter-assay accuracy with relative standard deviation (RSD) values ranging from -1% to 19%. Analytical validation parameters attested that in-tube SPME/UHPLC-MS/MS is an appropriate method to determine parabens in human milk samples to assess human exposure to these compounds. Analysis of breast milk samples from lactating women demonstrated that the proposed method is effective. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Gene trio signatures as molecular markers to predict response to doxorubicin cyclophosphamide neoadjuvant chemotherapy in breast cancerpatients

    Directory of Open Access Journals (Sweden)

    M.C. Barros Filho

    2010-12-01

    Full Text Available In breast cancer patients submitted to neoadjuvant chemotherapy (4 cycles of doxorubicin and cyclophosphamide, AC, expression of groups of three genes (gene trio signatures could distinguish responsive from non-responsive tumors, as demonstrated by cDNA microarray profiling in a previous study by our group. In the current study, we determined if the expression of the same genes would retain the predictive strength, when analyzed by a more accessible technique (real-time RT-PCR. We evaluated 28 samples already analyzed by cDNA microarray, as a technical validation procedure, and 14 tumors, as an independent biological validation set. All patients received neoadjuvant chemotherapy (4 AC. Among five trio combinations previously identified, defined by nine genes individually investigated (BZRP, CLPTM1,MTSS1, NOTCH1, NUP210, PRSS11, RPL37A, SMYD2, and XLHSRF-1, the most accurate were established by RPL37A, XLHSRF-1based trios, with NOTCH1 or NUP210. Both trios correctly separated 86% of tumors (87% sensitivity and 80% specificity for predicting response, according to their response to chemotherapy (82% in a leave-one-out cross-validation method. Using the pre-established features obtained by linear discriminant analysis, 71% samples from the biological validation set were also correctly classified by both trios (72% sensitivity; 66% specificity. Furthermore, we explored other gene combinations to achieve a higher accuracy in the technical validation group (as a training set. A new trio, MTSS1, RPL37 and SMYD2, correctly classified 93% of samples from the technical validation group (95% sensitivity and 80% specificity; 86% accuracy by the cross-validation method and 79% from the biological validation group (72% sensitivity and 100% specificity. Therefore, the combined expression of MTSS1, RPL37 and SMYD2, as evaluated by real-time RT-PCR, is a potential candidate to predict response to neoadjuvant doxorubicin and cyclophosphamide in breast cancer

  20. Combined SPECT/CT and PET/CT for breast imaging

    Energy Technology Data Exchange (ETDEWEB)

    Russo, Paolo [Università di Napoli Federico II, Dipartimento di Fisica, Via Cintia, Naples I-80126 (Italy); INFN Sezione di Napoli, Via Cintia, Naples I-80126 (Italy); Larobina, Michele [Istituto di Biostrutture e Bioimmagini, Consiglio Nazionale delle Ricerche, Via Tommaso De Amicis, 95, Naples I-80145 (Italy); Di Lillo, Francesca [Università di Napoli Federico II, Dipartimento di Fisica, Via Cintia, Naples I-80126 (Italy); INFN Sezione di Napoli, Via Cintia, Naples I-80126 (Italy); Del Vecchio, Silvana [Università di Napoli Federico II, Dipartimento di Scienze Biomediche Avanzate, Via Pansini, 5, Naples I-80131 (Italy); Mettivier, Giovanni, E-mail: mettivier@na.infn.it [Università di Napoli Federico II, Dipartimento di Fisica, Via Cintia, Naples I-80126 (Italy); INFN Sezione di Napoli, Via Cintia, Naples I-80126 (Italy)

    2016-02-11

    In the field of nuclear medicine imaging, breast imaging for cancer diagnosis is still mainly based on 2D imaging techniques. Three-dimensional tomographic imaging with whole-body PET or SPECT scanners, when used for imaging the breast, has performance limits in terms of spatial resolution and sensitivity, which can be overcome only with a dedicated instrumentation. However, only few hybrid imaging systems for PET/CT or SPECT/CT dedicated to the breast have been developed in the last decade, providing complementary functional and anatomical information on normal breast tissue and lesions. These systems are still under development and clinical trials on just few patients have been reported; no commercial dedicated breast PET/CT or SPECT/CT is available. This paper reviews combined dedicated breast PET/CT and SPECT/CT scanners described in the recent literature, with focus on their technological aspects.

  1. Income, productivity, and satisfaction of breast surgeons.

    Science.gov (United States)

    Bendorf, David C; Helmer, Stephen D; Osland, Jacqueline S; Tenofsky, Patty L

    2010-03-01

    The purpose of this study was to assess how the practice patterns of breast surgeons affect their income and job satisfaction. A 19-question survey regarding practice patterns and income and job satisfaction was mailed to all active US members of the American Society of Breast Surgeons. There were 772 responses. An increasing percentage of breast care was associated with lower incomes (P=.0001) and similar income satisfaction (P=.4517) but higher job satisfaction (P=.0001). The increasing proportion of breast care was also associated with fewer hours worked per week (P=.0001). Although incomes were lower in surgeons with a higher proportion of their practice in breast care, income satisfaction was not affected. Although cause and effect relationships between income and breast surgery are difficult to establish, several trends do emerge. Most significantly, we found that dedicated breast surgeons have higher job satisfaction ratings and similar income satisfaction despite lower incomes. Copyright (c) 2010 Elsevier Inc. All rights reserved.

  2. Evaluation of tilted cone-beam CT orbits in the development of a dedicated hybrid mammotomograph

    International Nuclear Information System (INIS)

    Madhav, P; Crotty, D J; Tornai, M P; McKinley, R L

    2009-01-01

    A compact dedicated 3D breast SPECT-CT (mammotomography) system is currently under development. In its initial prototype, the cone-beam CT sub-system is restricted to a fixed-tilt circular rotation around the patient's pendant breast. This study evaluated stationary-tilt angles for the CT sub-system that will enable maximal volumetric sampling and viewing of the breast and chest wall. Images of geometric/anthropomorphic phantoms were acquired using various fixed-tilt circular and 3D sinusoidal trajectories. The iteratively reconstructed images showed more distortion and attenuation coefficient inaccuracy from tilted cone-beam orbits than from the complex trajectory. Additionally, line profiles illustrated cupping artifacts in planes distal to the central plane of the tilted cone-beam, otherwise not apparent for images acquired with complex trajectories. This indicates that undersampled cone-beam data may be an additional cause of cupping artifacts. High-frequency objects could be distinguished for all trajectories, but their shapes and locations were corrupted by out-of-plane frequency information. Although more acrylic balls were visualized with a fixed-tilt and nearly flat cone-beam at the posterior of the breast, 3D complex trajectories have less distortion and more complete sampling throughout the reconstruction volume. While complex trajectories would ideally be preferred, negatively fixed-tilt source-detector configuration demonstrates minimally distorted patient images.

  3. Study of association and molecular analysis of human papillomavirus in breast cancer of Indian patients: Clinical and prognostic implication.

    Directory of Open Access Journals (Sweden)

    Saimul Islam

    Full Text Available Human papillomavirus (HPV causes tumors primarily Cervical cancer. Recently, inconsistent reports came up in Breast cancer (BC too. In India, despite treatment 70,218 BC patients die each year. So, we explored the association of HPV, if any, with BC prognosis in Indian pre-therapeutic (PT and Neo-adjuvant chemotherapy (NACT patients with subsequent analysis of HPV profile.HPV prevalence was checked and analysis of physical status, copy number, genome variation, promoter methylation and expression (mRNA and protein of the prevalent subtype was done.High prevalence of HPV was observed in both PT (64.0% and NACT (71.0% cases with significant association with younger (20-45 yrs PT patients. Interestingly, HPV infection was significantly increased from adjacent normal breast (9.5%, 2/21, fibro adenomas (30%, 3/10 to tumors (64.8%, 203/313 samples. In both PT and NACT cases, HPV16 was the most prevalent subtype (69.0% followed by HPV18 and HPV33. Survival analysis illustrated hrHPV infected PT patients had worst prognosis. So, detailed analysis of HPV16 profile was done which showed Europian-G350 as the most frequent HPV16 variant along with high rate of integration. Moreover, low copy number and hyper-methylation of P97 early promoter were concordant with low HPV16 E6 and E7 mRNA and protein expression. Notably, four novel variations (KT020838, KT020840, KT020841 and KT020839 in the LCR region and two (KT020836 and KT020837 in the E6 region were identified for the first time along with two novel E6^E7*I (KU199314 and E6^E7*II (KU199315 fusion transcript variants.Thus, significant association of hrHPV with prognosis of Indian BC patients led to additional investigation of HPV16 profile. Outcomes indicated a plausible role of HPV in Indian BC patients.

  4. Cost effective nuclear commercial grade dedication

    International Nuclear Information System (INIS)

    Maletz, J.J.; Marston, M.J.

    1991-01-01

    This paper describes a new computerized database method to create/edit/view specification technical data sheets (mini-specifications) for procurement of spare parts for nuclear facility maintenance and to develop information that could support possible future facility life extension efforts. This method may reduce cost when compared with current manual methods. The use of standardized technical data sheets (mini-specifications) for items of the same category improves efficiency. This method can be used for a variety of tasks, including: Nuclear safety-related procurement; Non-safety related procurement; Commercial grade item procurement/dedication; Evaluation of replacement items. This program will assist the nuclear facility in upgrading its procurement activities consistent with the recent NUMARC Procurement Initiative. Proper utilization of the program will assist the user in assuring that the procured items are correct for the applications, provide data to assist in detecting fraudulent materials, minimize human error in withdrawing database information, improve data retrievability, improve traceability, and reduce long-term procurement costs

  5. Virtual Machine Scheduling in Dedicated Computing Clusters

    CERN Document Server

    Boettger, Stefan; Zicari, V Roberto

    2014-01-08

    Time-critical applications process a continuous stream of input data and have to meet specific timing constraints. A common approach to ensure that such an application satisfies its constraints is over-provisioning: The application is deployed in a dedicated cluster environment with enough processing power to achieve the target performance for every specified data input rate. This approach comes with a drawback: At times of decreased data input rates, the cluster resources are not fully utilized. A typical use case is the HLT-Chain application that processes physics data at runtime of the ALICE experiment at CERN. From a perspective of cost and efficiency it is desirable to exploit temporarily unused cluster resources. Existing approaches aim for that goal by running additional applications. These approaches, however, a) lack in flexibility to dynamically grant the time-critical application the resources it needs, b) are insufficient for isolating the time-critical application from harmful side-effects i...

  6. A subjective scheduler for subjective dedicated networks

    Science.gov (United States)

    Suherman; Fakhrizal, Said Reza; Al-Akaidi, Marwan

    2017-09-01

    Multiple access technique is one of important techniques within medium access layer in TCP/IP protocol stack. Each network technology implements the selected access method. Priority can be implemented in those methods to differentiate services. Some internet networks are dedicated for specific purpose. Education browsing or tutorial video accesses are preferred in a library hotspot, while entertainment and sport contents could be subjects of limitation. Current solution may use IP address filter or access list. This paper proposes subjective properties of users or applications are used for priority determination in multiple access techniques. The NS-2 simulator is employed to evaluate the method. A video surveillance network using WiMAX is chosen as the object. Subjective priority is implemented on WiMAX scheduler based on traffic properties. Three different traffic sources from monitoring video: palace, park, and market are evaluated. The proposed subjective scheduler prioritizes palace monitoring video that results better quality, xx dB than the later monitoring spots.

  7. Conception of comics dedicated to optics learning

    Science.gov (United States)

    Machemy, Jacques; Bousquet, Bruno

    2015-10-01

    Optics' teaching is commonly based on the use of lessons including several mathematical tools. For example, ray tracing can be described through matrix algebra, and interference and polarization can be supported by the use of complex numbers. Thus, the numerous mathematical descriptions included in the optics' lessons represent a real difficulty for students having insufficient skills in mathematics. Moreover, despite of very impressive optical effects one can observe in real life, e.g. rainbows, their description in optics' courses is often considered as too academic and boring, and finally not really exciting. In this context, we have invented a new type of comics dedicated to optics' learning. Based on a dialogue between two imaginary characters, one considered as the young student and the other one as the old teacher, we have chosen to reduce the role of mathematics and to mix realistic and unrealistic elements in the drawing to complete the explanations faster. Starting from reflection and refraction, the Snell's laws then allow for describing natural phenomena such as mirage and rainbow as well as technical points such as light propagation into an optical fiber and the measurement of the refraction index. The first volume presented here will be evaluated during the fall semester 2015 in different high schools and at university through a linked survey and the students will also get access to an online version while the following parts are in preparation.

  8. CSMB | Center For Structural Molecular Biology

    Data.gov (United States)

    Federal Laboratory Consortium — The Center for Structural Molecular Biologyat ORNL is dedicated to developing instrumentation and methods for determining the 3-dimensional structures of proteins,...

  9. Breast composition: Measurement and clinical use

    International Nuclear Information System (INIS)

    Ekpo, E.U.; Hogg, P.; Highnam, R.; McEntee, M.F.

    2015-01-01

    Breast density is a measure of the extent of radiodense fibroglandular tissue in the breast. The risk of developing breast cancer and the risk of missing cancer at screening rise with higher breast density. In this paper, the historical background to breast density measurement is outlined and current evidence based practice is explained. The relevance of breast density knowledge to mammographic practice and image interpretation is considered in the light of clinical assessment and notification of mammographic breast density (MBD). The current work also discusses risk stratification for decision-making regarding screening frequency and better modalities for earlier detection of breast cancer in the dense breast. Automated volumetric approaches are explained while ultrasound, digital breast tomosynthesis, molecular breast imaging, and magnetic resonance imaging are introduced as valuable adjuncts to digital mammography for imaging the dense breast. The work concludes on the important note that screened women should be notified of their breast density, and such notification should be accompanied with clear and adequate information about breast density and cancer risk, strategies associated with lower MBD, as well as best screening intervals and pathways for women with dense breasts. Adoption of these strategies may be crucial to early detection and treatment of cancer and improving survival from the disease. - Highlights: • Breast density is associated with breast cancer risk and interval breast cancer. • Breast density can be measured manually or automatically. • Radiographic exposure factors impact on breast density measurements. • Dense breast often require imaging with three-dimensional modalities. • National breast density data could enable breast cancer risk stratification.

  10. miRNA-135b Contributes to Triple Negative Breast Cancer Molecular Heterogeneity: Different Expression Profile in Basal-like Versus non-Basal-like Phenotypes.

    Science.gov (United States)

    Uva, Paolo; Cossu-Rocca, Paolo; Loi, Federica; Pira, Giovanna; Murgia, Luciano; Orrù, Sandra; Floris, Matteo; Muroni, Maria Rosaria; Sanges, Francesca; Carru, Ciriaco; Angius, Andrea; De Miglio, Maria Rosaria

    2018-01-01

    The clinical and genetic heterogeneity of Triple Negative Breast Cancer (TNBC) and the lack of unambiguous molecular targets contribute to the inadequacy of current therapeutic options for these variants. MicroRNAs (miRNA) are a class of small highly conserved regulatory endogenous non-coding RNA, which can alter the expression of genes encoding proteins and may play a role in the dysregulation of cellular pathways. Our goal was to improve the knowledge of the molecular pathogenesis of TNBC subgroups analyzing the miRNA expression profile, and to identify new prognostic and predictive biomarkers. We conducted a human miRNome analysis by TaqMan Low Density Array comparing different TNBC subtypes, defined by immunohistochemical basal markers EGFR and CK5/6. RT-qPCR confirmed differential expression of microRNAs. To inspect the function of the selected targets we perform Gene Ontology and KEGG enrichment analysis. We identified a single miRNA signature given by miR-135b expression level, which was strictly related to TNBC with basal-like phenotype. miR-135b target analysis revealed a role in the TGF-beta, WNT and ERBB pathways. A significant positive correlation was identified between neoplastic proliferative index and miR-135b expression. These findings confirm the oncogenic roles of miR-135b in the pathogenesis of TNBC expressing basal markers. A potential negative prognostic role of miR-135b overexpression might be related to the positive correlation with high proliferative index. Our study implies potential clinical applications: miR-135b could be a potential therapeutic target in basal-like TNBCs.

  11. Integrated molecular analysis of Tamoxifen-resistant invasive lobular breast cancer cells identifies MAPK and GRM/mGluR signaling as therapeutic vulnerabilities.

    Science.gov (United States)

    Stires, Hillary; Heckler, Mary M; Fu, Xiaoyong; Li, Zhao; Grasso, Catherine S; Quist, Michael J; Lewis, Joseph A; Klimach, Uwe; Zwart, Alan; Mahajan, Akanksha; Győrffy, Balázs; Cavalli, Luciane R; Riggins, Rebecca B

    2018-08-15

    Invasive lobular breast cancer (ILC) is an understudied malignancy with distinct clinical, pathological, and molecular features that distinguish it from the more common invasive ductal carcinoma (IDC). Mounting evidence suggests that estrogen receptor-alpha positive (ER+) ILC has a poor response to Tamoxifen (TAM), but the mechanistic drivers of this are undefined. In the current work, we comprehensively characterize the SUM44/LCCTam ILC cell model system through integrated analysis of gene expression, copy number, and mutation, with the goal of identifying actionable alterations relevant to clinical ILC that can be co-targeted along with ER to improve treatment outcomes. We show that TAM has several distinct effects on the transcriptome of LCCTam cells, that this resistant cell model has acquired copy number alterations and mutations that impinge on MAPK and metabotropic glutamate receptor (GRM/mGluR) signaling networks, and that pharmacological inhibition of either improves or restores the growth-inhibitory actions of endocrine therapy. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  12. Special Issue Dedication to Stephen H. Schneider

    Directory of Open Access Journals (Sweden)

    Paul Baer

    2011-12-01

    Full Text Available It is with both pleasure and sadness that we dedicate this special climate change issue of Portal to the late Dr. Stephen H. Schneider. Steve, as he was known to his friends and colleagues, was as rare a bird as any he sought out in his passion as a birdwatcher. A brilliant climate scientist, author of countless books and papers, path breaking inter-disciplinarian, eminent public communicator, mentor to dozens of young scholars; the list of roles and adulatory adjectives could fill an IPCC special report. Steve would have appreciated this special issue, with its multidisciplinary approach, and its quest for solutions based on analytical scholarship. He understood better than most the inseparability of normative and descriptive concerns, the need for academics and scientists of all kinds to be involved with public processes of communication, policy design and deliberation. While his last book was called “Science as a Contact Sport,” the unspoken title of his career might have been “Science as a Public Service.” He was endlessly testifying, consulting and giving interviews, and encouraged others to learn to do the same. Notwithstanding a battle with lymphoma in the last decade (chronicled in the wonderful book The Patient from Hell, Steve maintained a frenetic level of activity and was still going strong when he was felled by a pulmonary embolism in July of 2010 at age 65. He leaves behind a legacy embodied in his publications, institutions like the IPCC and the journal Climatic Change, and in the hearts and minds of the countless persons he interacted with, mentored, and loved. Exuberant, passionate, full of warmth and good humor, Steve was a mensch among mensches. He will be sorely missed. Paul Baer, with the assistance of Terry Root and Ian McGregor.

  13. Multimodality Registration without a Dedicated Multimodality Scanner

    Directory of Open Access Journals (Sweden)

    Bradley J. Beattie

    2007-03-01

    Full Text Available Multimodality scanners that allow the acquisition of both functional and structural image sets on a single system have recently become available for animal research use. Although the resultant registered functional/structural image sets can greatly enhance the interpretability of the functional data, the cost of multimodality systems can be prohibitive, and they are often limited to two modalities, which generally do not include magnetic resonance imaging. Using a thin plastic wrap to immobilize and fix a mouse or other small animal atop a removable bed, we are able to calculate registrations between all combinations of four different small animal imaging scanners (positron emission tomography, single-photon emission computed tomography, magnetic resonance, and computed tomography [CT] at our disposal, effectively equivalent to a quadruple-modality scanner. A comparison of serially acquired CT images, with intervening acquisitions on other scanners, demonstrates the ability of the proposed procedures to maintain the rigidity of an anesthetized mouse during transport between scanners. Movement of the bony structures of the mouse was estimated to be 0.62 mm. Soft tissue movement was predominantly the result of the filling (or emptying of the urinary bladder and thus largely constrained to this region. Phantom studies estimate the registration errors for all registration types to be less than 0.5 mm. Functional images using tracers targeted to known structures verify the accuracy of the functional to structural registrations. The procedures are easy to perform and produce robust and accurate results that rival those of dedicated multimodality scanners, but with more flexible registration combinations and while avoiding the expense and redundancy of multimodality systems.

  14. Identification of Novel Molecular Targets for Pleckstrin Homology (PH) Domains Found in Oncogenes Implicated in Breast Cancer

    Science.gov (United States)

    2008-03-01

    roles as a positive regulator of IL- 2 gene induction in T cells (Deckert et al, 1998), NK cell-mediated cytotoxicity (Jevremovic et al, 2001), and FcRI...Identification of a gene encoding a human oxysterol-binding protein-homologue: a potential general molecular marker for blood dissemination of solid...Biol. 6(5), 384-385. Scanlan, MJ, Gout , I, Gordon, CM, Williamson, B, Stockert, E, Gure, AO, Jager, D, Chen, YT, Mackay, A, O’Hare, MJ, and Old LJ

  15. Breast Tomosynthesis

    Science.gov (United States)

    ... in distinguishing non-cancerous breast conditions from breast cancers. Breast implants may also impede accurate mammogram readings because both ... view as much as possible without rupturing the implant. top of ... discuss breast cancer screening options with their doctors: Breast Density and ...

  16. Hereditary breast cancer

    DEFF Research Database (Denmark)

    Larsen, Martin J; Thomassen, Mads; Gerdes, Anne-Marie

    2014-01-01

    Pathogenic mutations in BRCA1 or BRCA2 are only detected in 25% of families with a strong history of breast cancer, though hereditary factors are expected to be involved in the remaining families with no recognized mutation. Molecular characterization is expected to provide new insight...... into the tumor biology to guide the search of new high-risk alleles and provide better classification of the growing number of BRCA1/2 variants of unknown significance (VUS). In this review, we provide an overview of hereditary breast cancer, its genetic background, and clinical implications, before focusing...... on the pathologically and molecular features associated with the disease. Recent transcriptome and genome profiling studies of tumor series from BRCA1/2 mutation carriers as well as familial non-BRCA1/2 will be discussed. Special attention is paid to its association with molecular breast cancer subtypes as well...

  17. Elevated Levels of Serum Tumor Markers CEA and CA15-3 Are Prognostic Parameters for Different Molecular Subtypes of Breast Cancer

    OpenAIRE

    Shao, Yingbo; Sun, Xianfu; He, Yaning; Liu, Chaojun; Liu, Hui

    2015-01-01

    Background & Aims The utility of measuring carcinoembryonic antigen(CEA) and cancer antigen 15-3 (CA15-3) levels in patients with breast cancer remains controversial. The present study aims to investigate the prognostic value of preoperative serum CEA and CA15-3 levels in breast cancer patients. Methods Serum preoperative CEA and CA 15-3 concentration levels were measured in a total of 432 breast cancer patients. The association of tumor markers levels with clinicopathological parameters and ...

  18. Use of commercial grade item dedication to reduce procurement costs

    International Nuclear Information System (INIS)

    Rosch, F.

    1995-01-01

    In the mid-1980s, the Nuclear Regulatory Industry (NRC) began inspecting utility practices of procuring and dedicating commercial grade items intended for plant safety-related applications. As a result of the industry efforts to address NRC concerns, nuclear utilities have enhanced existing programs and procedures for dedication of commercial grade items. Though these programs were originally enhanced to meet NRC concerns, utilities have discovered that the dedication of commercial grade items can also reduce overall procurement costs. This paper will discuss the enhancement of utility dedication programs and demonstrates how utilities have utilized them to reduce procurement costs

  19. Breast Cancer Immunotherapy

    Institute of Scientific and Technical Information of China (English)

    JuhuaZhou; YinZhong

    2004-01-01

    Breast cancer is a leading cause of cancer-related deaths in women worldwide. Although tumorectomy, radiotherapy, chemotherapy and hormone replacement therapy have been used for the treatment of breast cancer, there is no effective therapy for patients with invasive and metastatic breast cancer. Immunotherapy may be proved effective in treating patients with advanced breast cancer. Breast cancer immunotherapy includes antibody based immunotherapy, cancer vaccine immunotherapy, adoptive T cell transfer immunotherapy and T cell receptor gene transfer immunotherapy. Antibody based immunotherapy such as the monoclonal antibody against HER-2/neu (trastuzumab) is successfully used in the treatment of breast cancer patients with over-expressed HER-2/neu, however, HER-2/neu is over-expressed only in 25-30% of breast cancer patients. Cancer vaccine immunotherapy is a promising method to treat cancer patients. Cancer vaccines can be used to induce specific anti-tumor immunity in breast cancer patients, but cannot induce objective tumor regression. Adoptive T cell transfer immunotherapy is an effective method in the treatment of melanoma patients. Recent advances in anti-tumor T cell generation ex vivo and limited clinical trial data have made the feasibility of adoptive T cell transfer immunotherapy in the treatment of breast cancer patients. T cell receptor gene transfer can redirect the specificity of T cells. Chimeric receptor, scFv(anti-HER-2/neu)/zeta receptor, was successfully used to redirect cytotoxic T lymphocyte hybridoma cells to obtain anti-HER-2/neu positive tumor cells, suggesting the feasibility of treatment of breast cancer patients with T cell receptor gene transfer immunotherapy. Clinical trials will approve that immunotherapy is an effective method to cure breast cancer disease in the near future. Cellular & Molecular Immunology.

  20. AMYPdb: A database dedicated to amyloid precursor proteins

    Directory of Open Access Journals (Sweden)

    Delamarche Christian

    2008-06-01

    Full Text Available Abstract Background Misfolding and aggregation of proteins into ordered fibrillar structures is associated with a number of severe pathologies, including Alzheimer's disease, prion diseases, and type II diabetes. The rapid accumulation of knowledge about the sequences and structures of these proteins allows using of in silico methods to investigate the molecular mechanisms of their abnormal conformational changes and assembly. However, such an approach requires the collection of accurate data, which are inconveniently dispersed among several generalist databases. Results We therefore created a free online knowledge database (AMYPdb dedicated to amyloid precursor proteins and we have performed large scale sequence analysis of the included data. Currently, AMYPdb integrates data on 31 families, including 1,705 proteins from nearly 600 organisms. It displays links to more than 2,300 bibliographic references and 1,200 3D-structures. A Wiki system is available to insert data into the database, providing a sharing and collaboration environment. We generated and analyzed 3,621 amino acid sequence patterns, reporting highly specific patterns for each amyloid family, along with patterns likely to be involved in protein misfolding and aggregation. Conclusion AMYPdb is a comprehensive online database aiming at the centralization of bioinformatic data regarding all amyloid proteins and their precursors. Our sequence pattern discovery and analysis approach unveiled protein regions of significant interest. AMYPdb is freely accessible 1.

  1. Dedicated Beamline Facilities for Catalytic Research. Synchrotron Catalysis Consortium (SCC)

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Jingguang [Columbia Univ., New York, NY; Frenkel, Anatoly [Yeshiva Univ., New York, NY (United States); Rodriguez, Jose [Brookhaven National Lab. (BNL), Upton, NY (United States); Adzic, Radoslav [Brookhaven National Lab. (BNL), Upton, NY (United States); Bare, Simon R. [UOP LLC, Des Plaines, IL (United States); Hulbert, Steve L. [Brookhaven National Lab. (BNL), Upton, NY (United States); Karim, Ayman [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Mullins, David R. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Overbury, Steve [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2015-03-04

    Synchrotron spectroscopies offer unique advantages over conventional techniques, including higher detection sensitivity and molecular specificity, faster detection rate, and more in-depth information regarding the structural, electronic and catalytic properties under in-situ reaction conditions. Despite these advantages, synchrotron techniques are often underutilized or unexplored by the catalysis community due to various perceived and real barriers, which will be addressed in the current proposal. Since its establishment in 2005, the Synchrotron Catalysis Consortium (SCC) has coordinated significant efforts to promote the utilization of cutting-edge catalytic research under in-situ conditions. The purpose of the current renewal proposal is aimed to provide assistance, and to develop new sciences/techniques, for the catalysis community through the following concerted efforts: Coordinating the implementation of a suite of beamlines for catalysis studies at the new NSLS-II synchrotron source; Providing assistance and coordination for catalysis users at an SSRL catalysis beamline during the initial period of NSLS to NSLS II transition; Designing in-situ reactors for a variety of catalytic and electrocatalytic studies; Assisting experimental set-up and data analysis by a dedicated research scientist; Offering training courses and help sessions by the PIs and co-PIs.

  2. A mathematical prediction model incorporating molecular subtype for risk of non-sentinel lymph node metastasis in sentinel lymph node-positive breast cancer patients: a retrospective analysis and nomogram development.

    Science.gov (United States)

    Wang, Na-Na; Yang, Zheng-Jun; Wang, Xue; Chen, Li-Xuan; Zhao, Hong-Meng; Cao, Wen-Feng; Zhang, Bin

    2018-04-25

    Molecular subtype of breast cancer is associated with sentinel lymph node status. We sought to establish a mathematical prediction model that included breast cancer molecular subtype for risk of positive non-sentinel lymph nodes in breast cancer patients with sentinel lymph node metastasis and further validate the model in a separate validation cohort. We reviewed the clinicopathologic data of breast cancer patients with sentinel lymph node metastasis who underwent axillary lymph node dissection between June 16, 2014 and November 16, 2017 at our hospital. Sentinel lymph node biopsy was performed and patients with pathologically proven sentinel lymph node metastasis underwent axillary lymph node dissection. Independent risks for non-sentinel lymph node metastasis were assessed in a training cohort by multivariate analysis and incorporated into a mathematical prediction model. The model was further validated in a separate validation cohort, and a nomogram was developed and evaluated for diagnostic performance in predicting the risk of non-sentinel lymph node metastasis. Moreover, we assessed the performance of five different models in predicting non-sentinel lymph node metastasis in training cohort. Totally, 495 cases were eligible for the study, including 291 patients in the training cohort and 204 in the validation cohort. Non-sentinel lymph node metastasis was observed in 33.3% (97/291) patients in the training cohort. The AUC of MSKCC, Tenon, MDA, Ljubljana, and Louisville models in training cohort were 0.7613, 0.7142, 0.7076, 0.7483, and 0.671, respectively. Multivariate regression analysis indicated that tumor size (OR = 1.439; 95% CI 1.025-2.021; P = 0.036), sentinel lymph node macro-metastasis versus micro-metastasis (OR = 5.063; 95% CI 1.111-23.074; P = 0.036), the number of positive sentinel lymph nodes (OR = 2.583, 95% CI 1.714-3.892; P model based on the results of multivariate analysis was established to predict the risk of non

  3. Breast infection

    Science.gov (United States)

    Mastitis; Infection - breast tissue; Breast abscess ... must continue to breastfeed or pump to relieve breast swelling from milk production. In case if the abscess does not go away, needle aspiration under ultrasound ...

  4. Breast lump

    Science.gov (United States)

    ... with milk). These cysts can occur with breastfeeding. Breast abscess . These typically occur if you are breastfeeding or ... Breast infections are treated with antibiotics. Sometimes a breast abscess needs to be drained with a needle or ...

  5. Breast Diseases

    Science.gov (United States)

    ... bumps, and discharges (fluids that are not breast milk). If you have a breast lump, pain, discharge or skin irritation, see your health care provider. Minor and serious breast problems have similar ...

  6. Breast lift

    Science.gov (United States)

    ... and areola may be moved. Sometimes, women have breast augmentation (enlargement with implants) when they have a breast lift. Why the ... MD, FACS, general surgery practice specializing in breast cancer, Virginia Mason Medical Center, Seattle, WA. Also reviewed ...

  7. Breast cancer

    Science.gov (United States)

    ... can help you know how to prevent breast cancer. Breast implants, using antiperspirants, and wearing underwire bras do not increase the risk for breast cancer. There is also no evidence of a direct ...

  8. Fibroadenoma - breast

    Science.gov (United States)

    Breast lump - fibroadenoma; Breast lump - noncancerous; Breast lump - benign ... The cause of fibroadenomas is not known. They may be related to hormones. Girls who are going through puberty and women who are ...

  9. Breast reconstruction - implants

    Science.gov (United States)

    Breast implants surgery; Mastectomy - breast reconstruction with implants; Breast cancer - breast reconstruction with implants ... harder to find a tumor if your breast cancer comes back. Getting breast implants does not take as long as breast reconstruction ...

  10. Energy Secretary Dedicates ESIF at NREL | News | NREL

    Science.gov (United States)

    3 » Energy Secretary Dedicates ESIF at NREL Energy Secretary Dedicates ESIF at NREL September 18 prey. Enlarge image Energy Secretary Ernest Moniz (center) joins NREL Director Dan Arvizu (left) and newest Energy Department supercomputer. The high performance computer inside NREL's new Energy Systems

  11. Dedicated auxiliary power units for Hybrid Electric Vehicles

    NARCIS (Netherlands)

    Mourad, S.; Weijer, C.J.T. van de

    1998-01-01

    The use of a dedicated auxiliary power unit is essential to utilize the potential that hybrid vehicles offer for efficient and ultra-clean transportation. An example of a hybrid project at the TNO Road-Vehicles Research Institute shows the development and the results of a dedicated auxiliary power

  12. Coherence in Professional Education: Does It Foster Dedication and Identification?

    Science.gov (United States)

    Heggen, Kåre; Terum, Lars Inge

    2013-01-01

    This article examines the impact of professional education on students' dedication to and identification with a profession. The premise is that professional education is not only about knowledge acquisition and reasoning but also about attitudes and aspirations. In fostering dedication and identification, students' experiences of relevance seem to…

  13. Adipokines in human breast milk.

    Science.gov (United States)

    Kratzsch, Juergen; Bae, Yoon Ju; Kiess, Wieland

    2018-01-01

    The review describes the molecular characteristics of so far detected breast milk adipokines and ranks their breast milk level compared to the respective levels in maternal and infant blood. Moreover, analytical knowledge for measurements of breast milk adipokines will be delineated. Next, we summarized data about two main potential influencing factors on adipokine concentration in breast milk, maternal weight and pasteurization of milk. Finally, associations between adipokines in breast milk and weight gain in infants as well as the putative mechanisms for effects of breast milk adipokines on food intake and weight gain in later life will debated. Our findings suggest that a source of adipokines in human breast milk cannot be uniformly defined. In dependence on the ratio between serum and breast milk levels the major quantity of these proteins may be derived from peripheral tissues, from the breast tissue itself or from both. Thus, leptin and in part adiponectin levels in breast milk are dependent on a plenty of influencing factors with an important relevance of maternal anthropometric characteristics There is some evidence that leptin, adiponectin and ghrelin levels in breast milk may be associated with growth gain of infants and even with increased risk for being overweight during infancy or childhood. We hypothesize that a dysregulation in adipokine homeostasis in early life could promote obesity and metabolic disturbance in later life. Copyright © 2018 Elsevier Ltd. All rights reserved.

  14. Prognosis value of molecular sub-types in breast cancers free of ganglionary invasion after mastectomy and impact of radiotherapy; Valeur pronostique des sous-types moleculaires dans les cancers du sein indemnes d'envahissement ganglionnaire apres mastectomie et impact de la radiotherapie

    Energy Technology Data Exchange (ETDEWEB)

    Selz, J.; Stevens, D.; Jouanneau, L.; Labib, A.; Le Scodan, R. [Hopital Rene-Huguenin, Saint-Cloud (France)

    2011-10-15

    The authors report the assessment of the prognosis value in terms of local control of molecular subtypes in patients suffering from breast cancer without ganglionary invasion, and of their predictive value for adjuvant irradiation. Medical files of nearly 700 patients have been analyzed. Some had an irradiation after mastectomy, some hadn't. The distribution of molecular sub-types is indicated, and the relationship with relapse is examined. The different molecular sub-types do not allow sub-groups with high risk of relapse to be defined. Breast cancers of stage pN0 after mastectomy seem to have a very good prognosis. Short communication

  15. The role of postmastectomy radiotherapy in different molecular subtypes of breast cancer patients with T1 - T2 and one to three positive axillary nodes

    International Nuclear Information System (INIS)

    Wang Hao; Luo Yangkun; Wang Jie; Peng Ying; Wen Hao; Wang Weidong; Lang Jinyi

    2011-01-01

    Objective: To analyze the role of postmastectomy radiotherapy in different molecular subtypes of breast cancer patients with Stage T 1 -T 2 and one to three positive axillary nodes. Methods: A total of 436 breast cancer patients with T 1 -T 2 and one to three positive axillary lymph nodes treated with mastectomy and axillary dissection were retrospectively analyzed. Patients were grouped as the following four subtypes:Luminal A, Luminal B, Her 2 + and triple-negative. The local recurrence (LR), distant metastasis ( DM ), disease free survival (DFS) and overall survival (OS) rates were compared between patients with or without radiotherapy in univariate analyses. Multivariate analyses for LR were performed. Results: The follow-up rate was 86. 0%. In patients with Luminal A subtype, radiotherapy decreased the 5-year LR rate (4.6% vs 15.8%, χ 2 =5.74, P=0.017) but had no influences on DM, DFS or OS rates (17.2% vs 19.7%, χ 2 =0.17, P=0.682; 77.0% vs 67.1%, χ 2 =1.99, P=0.158 or 87.4% : 85.5%, χ 2 =0.12, P=0.733). In patients with Luminal B subtype, radiotherapy decreased the 5-year LR rate (3.7% vs 12. 1%, χ 2 =4.13, P =0.042), increased DFS and OS (84.0% vs 57.6% (χ 2 =14.61, P =0.000) and 91.4% vs 70. 7% (χ 2 =11.87, P =0.001), but had no influence on DM (12.3% vs 22.2%, χ 2 =2.97, P =0.085). In patients with Her 2 + subtype, radiotherapy decreased the 5-year LR rate (5.6% vs 31.0%, χ 2 =4.31, P=0.035) , increased DFS (61.1% vs 13.8%, χ 2 =11.44, P=0.001) ,but had no influence on DM and OS (27.8% vs 41.4%, χ 2 =0.89, P =0.345 and 66.7% vs 48.3%, χ 2 =1.52, P =0.218). In patients with triple-negative subtype, radiotherapy had no influence in LR, DM, DFS or OS (8.7% vs 26.1%, χ 2 =2.42, P=0.120; 39.1% vs 47.8%, χ 2 =0.35, P=0.552; 52.2% vs 26.1%, χ 2 =3.29, P =0.070 or 65.2% vs 56.5%, χ 2 =0.37, P =0.546). Tumor size and radiotherapy were independent prognostic factors for LR rate in multivariate analyses (χ 2 =4.76, P =0.029 and χ 2 =8.06, P =0

  16. Isolation of Taxol-Producing Endophytic Fungi from Iranian Yew Through Novel Molecular Approach and Their Effects on Human Breast Cancer Cell Line.

    Science.gov (United States)

    Kasaei, Abdollah; Mobini-Dehkordi, Mohsen; Mahjoubi, Foruzandeh; Saffar, Behnaz

    2017-06-01

    Taxol or paclitaxel, an approved drug by the Food and Drug Administration, is being used for the treatment of human cancers. This study aimed to isolate and determine different species of native endophytic fungi from Iranian Taxus baccata (yew) plants located in the northern forests of Iran. To do so, a novel molecular screening approach was performed for 50 isolated endophytic fungi through amplification of exon No. 1 of taxadine synthase as a key gene in taxol production pathway. We used effective colony-polymerase chain reaction technique for rapid screening of potent taxol-producing fungi instead of genomic DNA extraction. Production of taxol was performed in batch culture by selected fungi individually and produced taxol was assayed quantitatively by high-performance liquid chromatography using standard taxanes. We found that only six fungi could produce taxol and baccatin III. Interestingly, after 7 days of incubation, the highest level of taxol was found to be 129 and that of baccatin 139.2 mg/kg dw for two native isolated Cladosporium sp. named F1 and F3. The fungal taxols could decrease cell viability in MTT assay same as commercial taxol. The fungal taxols semi-quantitatively showed antimitotic effects on MCF-7 cells as human breast cancer cell line. The expression of bcl-2 anti-apoptotic gene, in contrast to bax pro-apoptotic gene, significantly decreased after treatment by standard and fungal taxols. As fungal taxol was produced simpler than other methods and could significantly affect viability and specific genes expression profile, it is recommended that using of taxol-producing fungi from Iranian yew could be a safe and confident procedure to overcome challenges of using other methods.

  17. Strategy to find molecular signatures in a small series of rare cancers: validation for radiation-induced breast and thyroid tumors.

    Directory of Open Access Journals (Sweden)

    Nicolas Ugolin

    Full Text Available Methods of classification using transcriptome analysis for case-by-case tumor diagnosis could be limited by tumor heterogeneity and masked information in the gene expression profiles, especially as the number of tumors is small. We propose a new strategy, EMts_2PCA, based on: 1 The identification of a gene expression signature with a great potential for discriminating subgroups of tumors (EMts stage, which includes: a a learning step, based on an expectation-maximization (EM algorithm, to select sets of candidate genes whose expressions discriminate two subgroups, b a training step to select from the sets of candidate genes those with the highest potential to classify training tumors, c the compilation of genes selected during the training step, and standardization of their levels of expression to finalize the signature. 2 The predictive classification of independent prospective tumors, according to the two subgroups of interest, by the definition of a validation space based on a two-step principal component analysis (2PCA. The present method was evaluated by classifying three series of tumors and its robustness, in terms of tumor clustering and prediction, was further compared with that of three classification methods (Gene expression bar code, Top-scoring pair(s and a PCA-based method. Results showed that EMts_2PCA was very efficient in tumor classification and prediction, with scores always better that those obtained by the most common methods of tumor clustering. Specifically, EMts_2PCA permitted identification of highly discriminating molecular signatures to differentiate post-Chernobyl thyroid or post-radiotherapy breast tumors from their sporadic counterparts that were previously unsuccessfully classified or classified with errors.

  18. AutoIHC-scoring: a machine learning framework for automated Allred scoring of molecular expression in ER- and PR-stained breast cancer tissue.

    Science.gov (United States)

    Tewary, S; Arun, I; Ahmed, R; Chatterjee, S; Chakraborty, C

    2017-11-01

    In prognostic evaluation of breast cancer Immunohistochemical (IHC) markers namely, oestrogen receptor (ER) and progesterone receptor (PR) are widely used. The expert pathologist investigates qualitatively the stained tissue slide under microscope to provide the Allred score; which is clinically used for therapeutic decision making. Such qualitative judgment is time-consuming, tedious and more often suffers from interobserver variability. As a result, it leads to imprecise IHC score for ER and PR. To overcome this, there is an urgent need of developing a reliable and efficient IHC quantifier for high throughput decision making. In view of this, our study aims at developing an automated IHC profiler for quantitative assessment of ER and PR molecular expression from stained tissue images. We propose here to use CMYK colour space for positively and negatively stained cell extraction for proportion score. Also colour features are used for quantitative assessment of intensity scoring among the positively stained cells. Five different machine learning models namely artificial neural network, Naïve Bayes, K-nearest neighbours, decision tree and random forest are considered for learning the colour features using average red, green and blue pixel values of positively stained cell patches. Fifty cases of ER- and PR-stained tissues have been evaluated for validation with the expert pathologist's score. All five models perform adequately where random forest shows the best correlation with the expert's score (Pearson's correlation coefficient = 0.9192). In the proposed approach the average variation of diaminobenzidine (DAB) to nuclear area from the expert's score is found to be 7.58%, as compared to 27.83% for state-of-the-art ImmunoRatio software. © 2017 The Authors Journal of Microscopy © 2017 Royal Microscopical Society.

  19. Proteomic classification of breast cancer.

    LENUS (Irish Health Repository)

    Kamel, Dalia

    2012-11-01

    Being a significant health problem that affects patients in various age groups, breast cancer has been extensively studied to date. Recently, molecular breast cancer classification has advanced significantly with the availability of genomic profiling technologies. Proteomic technologies have also advanced from traditional protein assays including enzyme-linked immunosorbent assay, immunoblotting and immunohistochemistry to more comprehensive approaches including mass spectrometry and reverse phase protein lysate arrays (RPPA). The purpose of this manuscript is to review the current protein markers that influence breast cancer prediction and prognosis and to focus on novel advances in proteomic classification of breast cancer.

  20. ROS-dependent mitochondria molecular mechanisms underlying antitumor activity of Pleurotus abalonus acidic polysaccharides in human breast cancer MCF-7 cells.

    Directory of Open Access Journals (Sweden)

    Xiaolong Shi

    Full Text Available BACKGROUND: A greater reduction in cancer risk associated with mushroom diet rich in fungus polysaccharides is generally accepted. Meanwhile, edible Pleurotus abalonus as a member of Abalone mushroom family is a popular nutritional supplement that purportedly prevents cancer occurrence. However, these anecdotal claims are supported by limited studies describing tumor-inhibitory responses to the promising polysaccharides, and the molecular mechanisms underlying these properties have not yet been elucidated. METHODOLOGY/PRINCIPAL FINDINGS: We here fractionated the crude polysaccharide preparation from the fruiting bodies of P. abalonus into three fractions, namely PAP-1, PAP-2 and PAP-3, and tested these fractions for antiproliferative activity in human breast cancer MCF-7 cells. The largest PAP-3, an acidic polysaccharide fraction with a molecular mass of 3.68×10(5 Da, was the most active in inhibiting MCF-7 cancer cells with an IC50 of 193 µg/mL. The changes in cell normal morphology were observed by DAPI staining and the PAP-3-induced apoptosis was confirmed by annexin V/propidium iodide staining. The apoptosis was involved in mitochondria-mediated pathway including the loss of mitochondrial membrane potential (Δψm, the increase of Bax/Bcl-2 ratio, caspase-9/3 activation, and poly(ADP-ribose polymerase (PARP degradation, as well as intracellular ROS production. PAP-3 also induced up-regulation of p53, and cell cycle arrest at the S phase. The incubation of MCF-7 cells with antioxidant superoxide dismutase (SOD and N-acetylcysteine (NAC significantly attenuated the ROS generation and apoptosis caused by PAP-3, indicating that intracellular ROS plays a pivotal role in cell death. CONCLUSIONS/SIGNIFICANCE: These findings suggest that the polysaccharides, especially acidic PAP-3, are very important nutritional ingredients responsible for, at least in part, the anticancer health benefits of P. abalonus via ROS-mediated mitochondrial apoptotic

  1. PIP breast implants: rupture rate and correlation with breast cancer.

    Science.gov (United States)

    Moschetta, M; Telegrafo, M; Cornacchia, I; Vincenti, L; Ranieri, V; Cirili, A; Rella, L; Stabile Ianora, A A; Angelelli, G

    2014-01-01

    To evaluate the incidence of Poly Implant Prosthése (PIP) rupture as assessed by magnetic resonance imaging (MRI), the prevalence of the detected signs and the potential correlation with breast carcinoma. 67 patients with silicone breast implants and clinical indications for breast MRI were evaluated for a total of 125 implants: 40 (32%) PIP in 21 patients and 85 non-PIP in 46 patients (68%), the latest considered as control group. A 1.5-T MR imaging device was used in order to assess implant integrity with dedicated sequences and in 6 cases a dynamic study was performed for characterizing breast lesions. Two radiologists with more than 5 years' experience in the field of MRI evaluated in consensus all MR images searching for the presence of clear signs of intra or extra-capsular implant rupture. 20/40 (50%) PIP implants presented signs of intra-capsular rupture: linguine sign in 20 cases (100%), tear-drop sign in 6 (30%). In 12/20 cases (60%), MRI signs of extra-capsular rupture were detected. In the control group, an intra-capsular rupture was diagnosed in 12/85 cases (14%) associated with extra-capsular one in 5/12 cases (42%). Among the six cases with suspected breast lesions, in 2/21 patients with PIP implants (10%) a breast carcinoma was diagnosed (mucinous carcinoma, n=1; invasive ductal carcinoma, n=1). In 4/46 patients (9%) with non-PIP implants, an invasive ductal carcinoma was diagnosed. The rupture rate of PIP breast implants is significantly higher than non-PIP (50% vs 14%). MRI represents the most accurate imaging tool for evaluating breast prostheses and the linguine sign is the most common MRI sign to be searched. The incidence of breast carcinoma does not significantly differ between the PIP and non-PIP implants and a direct correlation with breast cancer can not been demonstrated.

  2. Magnetic resonance imaging of breast. Actual technique and indications

    International Nuclear Information System (INIS)

    Tardivon, Anne

    2007-01-01

    Optimal breast MRI protocols are required using dedicated breast coils, high spatial resolution dynamic sequences (morphologic criteria are significantly more accurate than kinetic criteria) and bolus injection of contrast medium. Any abnormal MR enhancement must be described using BI-RADSMRI lexicon. Main indications of breast MRI are: suspicion of intra-capsular rupture (silicone implants), local relapse in a treated breast, search for breast cancer (metastatic axillary lymph nodes), locals staging of a breast cancer (dense breasts), follow-up of cancer under neoadjuvant chemotherapy, and screening in high-risk patients (gene mutation background). MRI is also useful for patients with unresolved problems at standard imaging (high negative predictive value of MRI). In patients with breast cancer, it is important to underline the need for radiologists to work with the multidisciplinary team and the ability to perform MR-guided biopsies for additional suspicious enhancements. (author) [es

  3. Editorial: A dedication to Professor Jan Evetts

    Science.gov (United States)

    Weber, Harald; Dew-Hughes, David; Campbell, Archie; Barber, Zoe; Somekh, Rob; Glowacki, Bartek

    2006-03-01

    A few days before the beginning of the 7th European Conference on Applied Superconductivity we learned that Professor Jan Evetts, a pioneer of superconductor research, a brilliant scientist, a wonderful person and a great personal friend, had passed away. We therefore decided to dedicate the 7th European Conference on Applied Superconductivity to the memory of Jan Evetts. The following citation is based on material provided by his former supervisor (D Dew-Hughes) and his closest co-workers in Cambridge. Professor Jan Edgar Evetts (1939-2005) Professor Jan Edgar Evetts (1939-2005) Jan Evetts passed away after losing his second battle with cancer on 24th August 2005. He made an outstanding series of contributions to the science of superconductivity and to the understanding of superconducting materials and was an indefatigable champion of the development of applications of superconductivity. The loss to the superconductivity community is incalculable, as attested by the many communications received from colleagues throughout the world. Jan was born on 31 March 1939, and attended the Dragon School in Oxford, and later Haileybury. He was awarded an exhibition to read Natural Sciences at Pembroke College, Cambridge. He entered the college in 1958 and took his BA degree in 1961. He then undertook a Certificate of Postgraduate Study in Physics under the supervision of Professor Neville Mott. He was the first student to undertake this newly-instituted course; the title of his thesis was `The Resistance of Transition Metals'. In 1962 he joined David Dew-Hughes' superconducting materials research group, along with Archie Campbell and Anant Narlikar. In fact it was Jan's enthusiasm for the proposed course of research that helped convince David that he should follow Professor Alan Cottrell's suggestion to apply metallurgical methodology to the study of the factors that controlled critical current density in the type II superconductors that were then under development for

  4. Elevated Levels of Serum Tumor Markers CEA and CA15-3 Are Prognostic Parameters for Different Molecular Subtypes of Breast Cancer.

    Science.gov (United States)

    Shao, Yingbo; Sun, Xianfu; He, Yaning; Liu, Chaojun; Liu, Hui

    2015-01-01

    The utility of measuring carcinoembryonic antigen(CEA) and cancer antigen 15-3 (CA15-3) levels in patients with breast cancer remains controversial. The present study aims to investigate the prognostic value of preoperative serum CEA and CA15-3 levels in breast cancer patients. Serum preoperative CEA and CA 15-3 concentration levels were measured in a total of 432 breast cancer patients. The association of tumor markers levels with clinicopathological parameters and outcomes were analyzed. Elevated serum levels of CEA and CA15-3 were identified in 47 (10.9%) and 60(13.9%) patients, respectively. Larger tumor size, advanced axillary lymph nodal and TNM stage exhibited higher proportion of elevated CEA and CA15-3 levels. The elevation of CEA levels was significantly greater in patients with HER2 positive tumors, and the elevation of CA15-3 levels was significantly greater in ER negative breast patients. Univariate and multivariate Cox's regression analysis revealed that elevated preoperative CEA and CA 15-3 levels were independent prognostic factors for DFS and OS. When considering the combination of both markers levels, patients with both elevated markers presented the worst survival. Independent prognostic significance of elevated preoperative serum CEA and CA15-3 levels were reconfirmed in Luminal B breast cancer. Preoperative serum levels of CEA and CA15-3 are independent prognostic parameters for breast cancer.

  5. Elevated Levels of Serum Tumor Markers CEA and CA15-3 Are Prognostic Parameters for Different Molecular Subtypes of Breast Cancer.

    Directory of Open Access Journals (Sweden)

    Yingbo Shao

    Full Text Available The utility of measuring carcinoembryonic antigen(CEA and cancer antigen 15-3 (CA15-3 levels in patients with breast cancer remains controversial. The present study aims to investigate the prognostic value of preoperative serum CEA and CA15-3 levels in breast cancer patients.Serum preoperative CEA and CA 15-3 concentration levels were measured in a total of 432 breast cancer patients. The association of tumor markers levels with clinicopathological parameters and outcomes were analyzed.Elevated serum levels of CEA and CA15-3 were identified in 47 (10.9% and 60(13.9% patients, respectively. Larger tumor size, advanced axillary lymph nodal and TNM stage exhibited higher proportion of elevated CEA and CA15-3 levels. The elevation of CEA levels was significantly greater in patients with HER2 positive tumors, and the elevation of CA15-3 levels was significantly greater in ER negative breast patients. Univariate and multivariate Cox's regression analysis revealed that elevated preoperative CEA and CA 15-3 levels were independent prognostic factors for DFS and OS. When considering the combination of both markers levels, patients with both elevated markers presented the worst survival. Independent prognostic significance of elevated preoperative serum CEA and CA15-3 levels were reconfirmed in Luminal B breast cancer.Preoperative serum levels of CEA and CA15-3 are independent prognostic parameters for breast cancer.

  6. President Roosevelt's 1940 Dedication of the First NCI Building

    Science.gov (United States)

    Watch this video excerpt of the dedication of the National Institute of Health, October 31, 1940. President Roosevelt spoke of the importance of the National Cancer Institute, which would be located in Building 6.

  7. Evaluating the use of dedicated swab for rapid antigen detection ...

    African Journals Online (AJOL)

    Evaluating the use of dedicated swab for rapid antigen detection testing in group a ... African Journal of Clinical and Experimental Microbiology ... Several generations of rapid antigen detection tests (RADTs) have been developed to facilitate ...

  8. Don't Forget About Dedicated Sea Mine Countermeasures

    National Research Council Canada - National Science Library

    Potts, Malcolm H

    2005-01-01

    .... Struggling through the Korean Conflict, the U.S. Navy began a slow improvement of MCM forces leading up to the first Gulf War where experiences led to the conclusion that a well equipped dedicated MCM force structure is essential...

  9. Minimizing Warehouse Space with a Dedicated Storage Policy

    Directory of Open Access Journals (Sweden)

    Andrea Fumi

    2013-07-01

    inevitably be supported by warehouse management system software. On the contrary, the proposed methodology relies upon a dedicated storage policy, which is easily implementable by companies of all sizes without the need for investing in expensive IT tools.

  10. Analysis of molecular subtypes for the increased HER2 equivocal cases caused by application of the updated 2013 ASCO/CAP HER2 testing guidelines in breast cancer.

    Science.gov (United States)

    Guo, Lei; Yuan, Pei; Zhang, Jing; Ling, Yun; Li, Wenbin; Zhao, Bohui; Ying, Jianming; Xuan, Lixue

    2017-11-01

    Accurate testing of the status of human epidermal growth factor receptor type 2 (HER2) is a prerequisite for HER2-directed therapy. The American Society of Clinical Oncology (ASCO) and the College of American Pathologists (CAP) published joint guideline recommendations for HER2 testing in breast cancer in 2007 and it was updated in 2013. We compared the HER2 gene amplification status based on these two guidelines and analyzed the molecular characteristics of the equivocal cases. A total of 1894 patient samples were analyzed for both immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). HER2 FISH amplification was examined and re-assessed using 2013 guidelines. According to the 2013 ASCO/CAP recommendations, 763 (40.3%) cases were classified as HER2 positive compared with 729 (38.5%) cases defined by 2007 guidelines. There was a significant increase of 6.1% in the proportion of HER2 FISH equivocal cases that were interpreted using ASCO/CAP 2013 (7.3%) compared with 2007 (1.2%) guidelines (P guidelines, 125 cases were IHC2+ and 13 cases were IHC1+. These 125 cases included 4 double equivocal cases which were defined as equivocal by both 2007 and 2013 guidelines and 121 cases whose status was changed from negative defined by 2007 guidelines to equivocal defined by 2013 guidelines. Compared with luminal A type and luminal B type respectively, these 121 equivocal cases demonstrated no significant difference with luminal B type in T stage and N stage (P = 0.192, P = 0.421). When we divided the luminal B type into two parts that included HER2 negative cases and HER2 positive cases, the equivocal cases also showed no significant difference with these two subtypes in T stage and N stage. Our study suggested that implementation of the revised ASCO/CAP 2013 guidelines resulted in an increase of 1.7% in overall HER2 positivity rate and of 6.1% in equivocal cases. Pathological analysis revealed that these equivocal cases exhibit similar biological

  11. Breast cancer screening controversies: who, when, why, and how?

    Science.gov (United States)

    Chetlen, Alison; Mack, Julie; Chan, Tiffany

    2016-01-01

    Mammographic screening is effective in reducing mortality from breast cancer. The issue is not whether mammography is effective, but whether the false positive rate and false negative rates can be reduced. This review will discuss controversies including the reduction in breast cancer mortality, overdiagnosis, the ideal screening candidate, and the optimal imaging modality for breast cancer screening. The article will compare and contrast screening mammography, tomosynthesis, whole-breast screening ultrasound, magnetic resonance imaging, and molecular breast imaging. Though supplemental imaging modalities are being utilized to improve breast cancer diagnosis, mammography still remains the gold standard for breast cancer screening. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Breast Gangrene

    Directory of Open Access Journals (Sweden)

    Husasin Irfan

    2011-08-01

    Full Text Available Abstract Background Breast gangrene is rare in surgical practice. Gangrene of breast can be idiopathic or secondary to some causative factor. Antibiotics and debridement are used for management. Acute inflammatory infiltrate, severe necrosis of breast tissue, necrotizing arteritis, and venous thrombosis is observed on histopathology. The aim of was to study patients who had breast gangrene. Methods A prospective study of 10 patients who had breast gangrene over a period of 6 years were analyzed Results All the patients in the study group were female. Total of 10 patients were encountered who had breast gangrene. Six patients presented with breast gangrene on the right breast whereas four had on left breast. Out of 10 patients, three had breast abscess after teeth bite followed by gangrene, one had iatrogenic trauma by needle aspiration of erythematous area of breast under septic conditions. Four had history of application of belladonna on cutaneous breast abscess and had then gangrene. All were lactating female. Amongst the rest two were elderly, one of which was a diabetic who had gangrene of breast and had no application of belladonna. All except one had debridement under cover of broad spectrum antibiotics. Three patients had grafting to cover the raw area. Conclusion Breast gangrene occurs rarely. Etiology is variable and mutifactorial. Teeth bite while lactation and the iatrogenic trauma by needle aspiration of breast abscess under unsterlised conditions could be causative. Uncontrolled diabetes can be one more causative factor for the breast gangrene. Belladonna application as a topical agent could be inciting factor. Sometimes gangrene of breast can be idiopathic. Treatment is antibiotics and debridement.

  13. Breast Exam

    Science.gov (United States)

    ... ends. What you can expect Begin with a visual examination of your breasts Sit or stand shirtless ... to the next section. If you have a disability that makes it difficult to examine your breasts ...

  14. Breast cancer

    African Journals Online (AJOL)

    A collaborative article gives an overview of breast cancer in LICs, ... approach to the problem; therefore they are published as two separate ... attached to the diagnosis of breast cancer. ... Their founding statement in its early form is included.

  15. A rare case of silicone mammary implant infection by Streptomyces spp. in a patient with breast reconstruction after mastectomy: taxonomic characterization using molecular techniques

    DEFF Research Database (Denmark)

    Manteca, Angel; Pelaez, Ana Isabel; del Mar Garcia-Suarez, Maria

    2009-01-01

    A Streptomyces sp. isolated from a patient who had had breast reconstruction after a mastectomy was identified at the species level by comparative sequence analysis of 16S ribosomal DNA (rDNA) and the hypervariable alpha-region of the 16S rDNA.......A Streptomyces sp. isolated from a patient who had had breast reconstruction after a mastectomy was identified at the species level by comparative sequence analysis of 16S ribosomal DNA (rDNA) and the hypervariable alpha-region of the 16S rDNA....

  16. Dedication increases productivity: an analysis of the implementation of a dedicated medical team in the emergency department.

    Science.gov (United States)

    Ramos, Pedro; Paiva, José Artur

    2017-12-01

    In several European countries, emergency departments (EDs) now employ a dedicated team of full-time emergency medicine (EM) physicians, with a distinct leadership and bed-side emergency training, in all similar to other hospital departments. In Portugal, however, there are still two very different models for staffing EDs: a classic model, where EDs are mostly staffed with young inexperienced physicians from different medical departments who take turns in the ED in 12-h shifts and a dedicated model, recently implemented in some hospitals, where the ED is staffed by a team of doctors with specific medical competencies in emergency medicine that work full-time in the ED. Our study assesses the effect of an intervention in a large academic hospital ED in Portugal in 2002, and it is the first to test the hypothesis that implementing a dedicated team of doctors with EM expertise increases the productivity and reduces costs in the ED, maintaining the quality of care provided to patients. A pre-post design was used for comparing the change on the organisational model of delivering care in our medical ED. All emergency medical admissions were tracked in 2002 (classic model with 12-h shift in the ED) and 2005/2006 (dedicated team with full-time EM physicians), and productivity, costs with medical human resources and quality of care measures were compared. We found that medical productivity (number of patients treated per hour of medical work) increased dramatically after the creation of the dedicated team (X 2 KW = 31.135; N = 36; p work reduced both in regular hours and overtime. Moreover, hospitalisation rates decreased and the length of stay in the ED increased significantly after the creation of the dedicated team. Implementing a dedicated team of doctors increased the medical productivity and reduced costs in our ED. Our findings have straightforward implication for Portuguese policymakers aiming at reducing hospital costs while coping with increased ED demand.

  17. Expression of HIF-1α and Markers of Angiogenesis Are Not Significantly Different in Triple Negative Breast Cancer Compared to Other Breast Cancer Molecular Subtypes: Implications for Future Therapy.

    Science.gov (United States)

    Yehia, Lamis; Boulos, Fouad; Jabbour, Mark; Mahfoud, Ziyad; Fakhruddin, Najla; El-Sabban, Marwan

    2015-01-01

    Triple negative breast cancer lacks estrogen, progesterone and epidermal growth factor receptors rendering it refractory to available targetedtherapies. TNBC is associated with central fibrosis and necrosis, both indicators of tumor hypoxia. Hypoxia inducible factor 1α is up-regulated under hypoxia and its expression is associated with induction of angiogenesis resulting in proliferation, aggressive tumor phenotype and metastasis. In this study we evaluate the potential use of HIF-1α as aTNBC-specific marker. 62 TNBC, 64 HER2+, and 64 hormone-receptors positive breast cancer cases were evaluated for central fibrosis and necrosis, HIF-1α, HIF-1β, VEGFR3, CD31 expression and microvessel density. RNA extraction from paraffin-embedded samples, followed by quantitative real-time polymerase chain reaction (qRT-PCR) evaluation of HIF-1α and VEGF transcripts was performed on 54 cases (18 from each subtype). HIF-1α protein was expressed in 35.5% TNBC, 45.3% HER2+and 25.0% ER+/PR+ (p = 0.055; χ2 test). PCRanalysis of subgroup of breast cancers, 84.2% expressed HIF-1α protein and its transcripts, while only 66.7% expressed VEGF transcripts simultaneously with the HIF-1α protein and its transcripts. Central fibrosis and necrosis was highest in TNBC (p = 0.015; χ2 test), while MVD was comparable among all groups (p = 0.928; χ2 test). VEGFR3 was highest in TNBC expressing HIF-1α. HIF-1β protein was expressed in 32.0% of HIF-1α(+), and in (44.3%) of HIF-1α(-) breast cancer cases (p = 0.033; χ2 test). Moreover, HIF-1α expression in cases with central fibrosis and necrosis was highest in the HER2+ followed by the TNBC (p = 0.156; χ2 test). A proportion of TNBC express HIF-1α but not in a significantly different manner from other breast cancer subtypes. The potential of anti-HIF-1α targeted therapy is therefore not a candidate for exclusive use in TNBC, but should be considered in all breast cancers, especially in the setting of clinically aggressive or

  18. Primary Neuroendocrine Carcinoma of Breast: A Rare Case Report

    African Journals Online (AJOL)

    Introduction. Primary neuroendocrine carcinoma (PNEC) of breast ... than 50% neoplastic tumor cells expressing neuroendocrine. (NE) markers .... subtype also concluded that molecular classification helps ... decreased disease free survival.

  19. 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. ...

  20. The diagnosis and management of pre-invasive breast disease: Promise of new technologies in understanding pre-invasive breast lesions

    International Nuclear Information System (INIS)

    Jeffrey, Stefanie S; Pollack, Jonathan R

    2003-01-01

    Array-based comparative genomic hybridization, RNA expression profiling, and proteomic analyses are new molecular technologies used to study breast cancer. Invasive breast cancers were originally evaluated because they provided ample quantities of DNA, RNA, and protein. The application of these technologies to pre-invasive breast lesions is discussed, including methods that facilitate their implementation. Data indicate that atypical ductal hyperplasia and ductal carcinoma in situ are precursor lesions molecularly similar to adjacent invasive breast cancer. It is expected that molecular technologies will identify breast tissue at risk for the development of unfavorable subtypes of invasive breast cancer and reveal strategies for targeted chemoprevention or eradication

  1. Operating dedicated data centers – is it cost-effective?

    International Nuclear Information System (INIS)

    Ernst, M; Hogue, R; Hollowell, C; Strecker-Kellog, W; Wong, A; Zaytsev, A

    2014-01-01

    The advent of cloud computing centres such as Amazon's EC2 and Google's Computing Engine has elicited comparisons with dedicated computing clusters. Discussions on appropriate usage of cloud resources (both academic and commercial) and costs have ensued. This presentation discusses a detailed analysis of the costs of operating and maintaining the RACF (RHIC and ATLAS Computing Facility) compute cluster at Brookhaven National Lab and compares them with the cost of cloud computing resources under various usage scenarios. An extrapolation of likely future cost effectiveness of dedicated computing resources is also presented.

  2. Operating Dedicated Data Centers - Is It Cost-Effective?

    Science.gov (United States)

    Ernst, M.; Hogue, R.; Hollowell, C.; Strecker-Kellog, W.; Wong, A.; Zaytsev, A.

    2014-06-01

    The advent of cloud computing centres such as Amazon's EC2 and Google's Computing Engine has elicited comparisons with dedicated computing clusters. Discussions on appropriate usage of cloud resources (both academic and commercial) and costs have ensued. This presentation discusses a detailed analysis of the costs of operating and maintaining the RACF (RHIC and ATLAS Computing Facility) compute cluster at Brookhaven National Lab and compares them with the cost of cloud computing resources under various usage scenarios. An extrapolation of likely future cost effectiveness of dedicated computing resources is also presented.

  3. Human Leukocyte Antigen (HLA) Genotype as a Contributor to Racial/Ethnic Differences in Breast Cancer: A Population-Based, Molecular Epidemiologic Study

    National Research Council Canada - National Science Library

    Glaser, Sally L

    2005-01-01

    ... some of its racial/ethnic variation. Therefore, for a population-based series of post-menopausal white, black and Hispanic breast cancer cases and controls, we are determining HLA class I (A, B) and class II (DR, DO) genotypes...

  4. Human Leukocyte Antigen (HLA) Genotype as a Contributor to Racial/Ethnic Differences in Breast Cancer: A Population-Based, Molecular Epidemiologic Study

    National Research Council Canada - National Science Library

    Glaser, Sally

    2004-01-01

    ... may explain some of its variation by race/ethnicity. Therefore, for a population-based series of white, black and Hispanic breast cancer cases and controls, we are determining: 1) HLA class I (A, B) and class II (DQ, DR...

  5. Impact of established prognostic factors and molecular subtype in very young breast cancer patients: pooled analysis of four EORTC randomized controlled trials

    NARCIS (Netherlands)

    van der Hage, Jos A.; Mieog, J. Sven D.; van de Velde, Cornelis J. H.; Putter, Hein; Bartelink, Harry; van de Vijver, Marc J.

    2011-01-01

    Young age at the time of diagnosis of breast cancer is an independent factor of poor prognosis. In many treatment guidelines, the recommendation is to treat young patients with adjuvant chemotherapy regardless of tumor characteristics. However, limited data on prognostic factors are available for

  6. Overexpression of molecular chaperons GRP78 and GRP94 in CD44(hi)/CD24(lo) breast cancer stem cells.

    Science.gov (United States)

    Nami, Babak; Ghasemi-Dizgah, Armin; Vaseghi, Akbar

    2016-01-01

    Breast cancer stem cell with CD44(hi)/CD24(lo) phonotype is described having stem cell properties and represented as the main driving factor in breast cancer initiation, growth, metastasis and low response to anti-cancer agents. Glucoseregulated proteins (GRPs) are heat shock protein family chaperons that are charged with regulation of protein machinery and modulation of endoplasmic reticulum homeostasis whose important roles in stem cell development and invasion of various cancers have been demonstrated. Here, we investigated the expression levels of GRP78 and GRP94 in CD44(hi)/CD24(lo) phenotype breast cancer stem cells (BCSCs). MCF7, T-47D and MDA-MB-231 breast cancer cell lines were used. CD44(hi)/CD24(lo) phenotype cell population were analyzed and sorted by fluorescence-activated cell sorting (FACS). Transcriptional and translational expression of GRP78 and GRP94 were investigated by western blotting and quantitative real time PCR. RESULTS showed different proportion of CD44(hi)/CD24(lo) phenotype cell population in their original bulk cells. The ranking of the cell lines in terms of CD44(hi)/CD24(lo) phenotype cell population was as MCF7hi)/CD24(lo) phenotype cells exhibited higher mRNA and protein expression level of GRP78 and GRP94 compared to their original bulk cells. Our results show a relationship between overexpression of GRP78 and GRP94 and exhibiting CD44hi/CD24lo phenotype in breast cancer cells. We conclude that upregulation of GRPs may be an important factor in the emergence of CD44hi/CD24lo phenotype BCSCs features.

  7. Regulation of the O-glycan-type Sialyl-Lewis X (sLex) Bio-synthesis Pathway during Cell Transformation Programs: Epithelial-Mesenchymal Transition (EMT) and Molecular Subtypes in Breast Carcinoma and Human T Cell Activation

    KAUST Repository

    AbuElela, Ayman

    2017-12-01

    During tumor progression and development of distant metastases, a subset of cancer cells undergoes transformation programs, such as epithelial-mesenchymal transition (EMT), to acquire enhanced migratory attributes to commence the metastatic cascade with the intension of achieving an active cell adhesion molecule-mediated organ-specific homing. Similarly, naive T cells reform the assemblage of their surface adhesion molecules during differentiation to activated T cells in order to successfully home to sites of inflammation and other extra-lymphoid organs for surveillance purposes. Sialyl-Lewis X (sLex) is well-known for mediating the homing of epithelial circulating tumor cellss (CTCs) and activated T cells to target sites through the interaction with endothelial selectins. Since glycan structures are not directly encoded by the genome, their expression is dependent on the glycosyltransferase (GT) expression and activity. Yet, the modulation of GTs during breast cancer transformation and in different molecular subtypes is still unknown. In addition, although the regulation of GTs during T cell activation is well-understood, the regulation at the epigenetic level is lacking. O-glycan-type sLex expression and E-selectin binding under static and flow conditions varies among molecular subtypes of breast cancer and upon the induction of EMT which is linked to the expression patterns of GTs. GTs displayed a significant prognostic value of in the association with the patients\\' survival profiles and in the ability to predict the breast cancer molecular subtypes from the expression data of a random patient sample. Also, GTs were able to differentiate between tumor and their normal counterparts as well as cancer types and glioblastoma subtypes. On the other hand, we studied the regulation of GTs in human CD4+ memory T cells compared to the naive cells at the epigenetic level. Memory T cell subsets demonstrated differential chromatin accessibility and histone marks within

  8. Pseudomonas aeruginosa burn wound infection in a dedicated ...

    African Journals Online (AJOL)

    Background. Pseudomonas aeruginosa infection is a major cause of morbidity in burns patients. There is a paucity of publications dealing with this infection in the paediatric population. We describe the incidence, microbiology and impact of P. aeruginosa infection in a dedicated paediatric burns unit. Methods.

  9. Dedicating time to volunteering : Values, engagement, and commitment to beneficiaries

    NARCIS (Netherlands)

    Shantz, A.; Saksida, T.; Alfes, K.

    2014-01-01

    A moderated mediation model was developed to explain the variation in the amount of time volunteers dedicate to their chosen voluntary cause. Data from 534 volunteers of an international aid and development agency in the United Kingdom revealed a positive relationship between prosocial values and

  10. Commercial Grade Item (CGI) Dedication for Leak Detection Relays

    International Nuclear Information System (INIS)

    KOCH, M.R.; JOHNS, B.R.

    1999-01-01

    This Test Plan provides a test method to dedicate the leak detection relays used on the new Pumping and Instrumentation Control (PIC) skids. The new skids are fabricated on-site. The leak detection system is a safety class system per the Authorization Basis

  11. Spectrograph dedicated to measuring tropospheric trace gas constituents from space

    NARCIS (Netherlands)

    Vries, J. de; Laan, E.C.; Deutz, A.F.; Escudero-Sanz, I.; Bokhove, H.; Hoegee, J.; Aben, I.; Jongma, R.; Landgraf, J.; Hasekamp, O.P.; Houweling, S.; Weele, M. van; Oss, R. van; Oord, G. van den; Levelt, P.

    2005-01-01

    Several organizations in the Netherlands are cooperating to develop user requirements and instrument concepts in the line of SCIAMACHY and OMI but with an increased focus on measuring tropospheric constituents from space. The concepts use passive spectroscopy in dedicated wavelength sections in the

  12. Performance of TCP over UMTS common and dedicated channels

    NARCIS (Netherlands)

    Lo, Anthony; Heijenk, Geert; Bruma, Cezar; Gameiro, A.

    2003-01-01

    Universal Mobile Telecommunications System (UMTS) is a third-generation cellular network that enables high-speed wireless Internet access. This paper investigates the performance of Transmission Control Protocol (TCP) over UMTS utilizing a common and four dedicated transport channels with bit rates

  13. [Advanced online search techniques and dedicated search engines for physicians].

    Science.gov (United States)

    Nahum, Yoav

    2008-02-01

    In recent years search engines have become an essential tool in the work of physicians. This article will review advanced search techniques from the world of information specialists, as well as some advanced search engine operators that may help physicians improve their online search capabilities, and maximize the yield of their searches. This article also reviews popular dedicated scientific and biomedical literature search engines.

  14. Virginia Tech's College Of Natural Resources Dedicates Cheatham Hall Expansion

    OpenAIRE

    Davis, Lynn

    2003-01-01

    Thanks to funding by private donors, Alyce Cheatham and her family of Portland, Oregon, Virginia Tech's College of Natural Resources will dedicate a much-needed, three-story addition to its current Cheatham Hall on Wednesday, March 19, at 2:30 p.m.

  15. Cost of a dedicated ART clinic | Harling | South African Medical ...

    African Journals Online (AJOL)

    Abstract. Background. The provision of antiretroviral therapy (ART) is being rolled out across South Africa. Little evidence exists on the cost of running clinics for ART provision. Objectives. To determine the cost per patient-month enrolled in an ART programme and per patient-visit for a dedicated, public-sector ART clinic in a ...

  16. Service differentiation in spare parts supply through dedicated stocks

    NARCIS (Netherlands)

    Alvarez, Elisa; van der Heijden, Matthijs C.; Zijm, Willem H.M.

    2012-01-01

    We investigate keeping dedicated stocks at customer sites in addition to stock kept at some central location as a tool for applying service differentiation in spare parts supply. We study the resulting two-echelon system in a multi-item setting, both under backordering and under emergency shipments

  17. A Molecular Case-Control Study on the Association of Melatonin Hormone and rs#10830963 Single Nucleotide Polymorphism in its Receptor MTNR1B Gene with Breast Cancer

    Directory of Open Access Journals (Sweden)

    Nadia A Abd El Moneim

    2015-01-01

    Full Text Available Background: The main function of the pineal hormone melatonin which is mediated via its two receptors, MTNR1A and MTNR1B, is to mediate dark signals in addition to anti-oxidation, immune system enhancement, protection from radiation, and anti-cancer functions. A common single nucleotide polymorphism in the MTNR1B gene is rs#10830963, which is well known as a risk factor for type 2 diabetes mellitus. This study intends to figure out the role of melatonin and its receptor MTNR1B gene rs#10830963 polymorphism in breast cancer incidence, diagnosis and prognosis. Methods: This study included 43 females with breast cancer and 45 apparently normal healthy females. Restriction fragment length polymorphism-PCR was used for amplification and genotyping of the MTNR1B gene rs#10830963 polymorphism in whole blood. Serum melatonin levels were measured using a ready-for-use radioimmunoassay kit. Results: For the MTNR1B gene rs#10830963 polymorphism, we observed a significantly higher GG genotype frequency among cases (72.1% than controls (13.3%, with a diagnostic sensitivity of 83.78% and specificity of 76.47%. The cases had a frequency of 11.6% for the CC genotype and 16.3% for the CG genotype which was significantly lower compared to controls that had a 44.4% frequency of the CC genotype and 42.2% frequency of the CG genotype. The GG genotype had a significant association with larger tumor volume (P=0.048. Serum melatonin levels were significantly lower among breast cancer patients than controls. Using the ROC curve analysis, serum melatonin showed a significant AUC (72.6%, P39.5 pg/ml. Conclusion: The risk for breast cancer incidence increased as the serum levels of melatonin decreased and in females homozygous for the G allele (GG genotype of the MTNR1B gene rs#10830963 polymorphism. The GG genotype was found to be associated with increased breast tumor volume as a marker of a poor prognosis breast cancer.

  18. Correlation of molecular subtypes of invasive ductal carcinoma of breast with glucose metabolism in FDG PET/CT: Based on the recommendations of the St. Gallen Consenesus Meeting 2013

    Energy Technology Data Exchange (ETDEWEB)

    Bae, Sang Kyun [Dept. of Nuclear Medicine, Haeundae Paik Hospital, University of Inje College of Medicine, Busan (Korea, Republic of); Lee, Sun Seong; Park, Yun Soo; Park, Ji Sun; Kim, Tae Hyun; Yoon, Hye Kyoung; Ahn, Hyo Jung; Lee, Seok Mo [Busan Paik Hospital, University of Inje College of Medicine, Busan (Korea, Republic of)

    2017-03-15

    This study aimed to investigate the relationship between the SUVmax of primary breast cancer lesions and the molecular subtypes based on the recommendations of the St. Gallen consensus meeting 2013. Clinical records of patients who underwent F-18 FDG PET/CT for initial staging of invasive ductal carcinoma (IDC) of the breast were reviewed. A total of 183 patients were included. SUV{sub max} was correlated with the molecular subtypes defined by the St. Gallen Consensus Meeting 2013, i.e., luminal A-like (LA), luminal B-like HER2 negative (LBHER2-), luminal B-like HER2 positive (LBHER2+), HER2 positive (HER2+), and triple negative (TN), and with the clinicohistopathologic characteristics. The molecular subtype was LA in 38 patients, LBHER2- in 72, LBHER2+ in 21, HER2+ in 30, and TN in 22. The mean SUV{sub max} in the LA, LBHER2-, LBHER2+, HER2+, and TN groups were 4.5 ± 2.3, 7.2 ± 4.9, 7.2 ± 4.3, 10.2 ± 5.5, and 8.8 ± 7.1, respectively. Although SUV{sub max} differed significantly among these subtypes (p < 0.001), the values showed a wide overlap. Optimal cut-off SUV{sub max} to differentiate LA from LBHER2-, LBHER2+, HER2+ and TN were 5.9, 5.8, 7.5, and 10.2 respectively, with area under curve (AUC) of 0.648, 0.709, 0.833, and 0.697 respectively. The cut-off value of 5.9 yielded the highest accuracy for differentiation between the LA and non-LA subtypes, with sensitivity, specificity, and AUC of 79.4 %, 57.9 %, and 0.704 respectively. The SUV{sub max} showed a significant correlation with the molecular subtype. Although SUV{sub max} measurements could be used along with immunohistochemical analysis for differentiating between molecular subtypes, its application to individual patients may be limited due to the wide overlaps in SUV{sub max}.

  19. Correlation of molecular subtypes of invasive ductal carcinoma of breast with glucose metabolism in FDG PET/CT: Based on the recommendations of the St. Gallen Consenesus Meeting 2013

    International Nuclear Information System (INIS)

    Bae, Sang Kyun; Lee, Sun Seong; Park, Yun Soo; Park, Ji Sun; Kim, Tae Hyun; Yoon, Hye Kyoung; Ahn, Hyo Jung; Lee, Seok Mo

    2017-01-01

    This study aimed to investigate the relationship between the SUVmax of primary breast cancer lesions and the molecular subtypes based on the recommendations of the St. Gallen consensus meeting 2013. Clinical records of patients who underwent F-18 FDG PET/CT for initial staging of invasive ductal carcinoma (IDC) of the breast were reviewed. A total of 183 patients were included. SUV_m_a_x was correlated with the molecular subtypes defined by the St. Gallen Consensus Meeting 2013, i.e., luminal A-like (LA), luminal B-like HER2 negative (LBHER2-), luminal B-like HER2 positive (LBHER2+), HER2 positive (HER2+), and triple negative (TN), and with the clinicohistopathologic characteristics. The molecular subtype was LA in 38 patients, LBHER2- in 72, LBHER2+ in 21, HER2+ in 30, and TN in 22. The mean SUV_m_a_x in the LA, LBHER2-, LBHER2+, HER2+, and TN groups were 4.5 ± 2.3, 7.2 ± 4.9, 7.2 ± 4.3, 10.2 ± 5.5, and 8.8 ± 7.1, respectively. Although SUV_m_a_x differed significantly among these subtypes (p < 0.001), the values showed a wide overlap. Optimal cut-off SUV_m_a_x to differentiate LA from LBHER2-, LBHER2+, HER2+ and TN were 5.9, 5.8, 7.5, and 10.2 respectively, with area under curve (AUC) of 0.648, 0.709, 0.833, and 0.697 respectively. The cut-off value of 5.9 yielded the highest accuracy for differentiation between the LA and non-LA subtypes, with sensitivity, specificity, and AUC of 79.4 %, 57.9 %, and 0.704 respectively. The SUV_m_a_x showed a significant correlation with the molecular subtype. Although SUV_m_a_x measurements could be used along with immunohistochemical analysis for differentiating between molecular subtypes, its application to individual patients may be limited due to the wide overlaps in SUV_m_a_x

  20. Breast Reconstruction After Mastectomy

    Science.gov (United States)

    ... Cancer Prevention Genetics of Breast & Gynecologic Cancers Breast Cancer Screening Research Breast Reconstruction After Mastectomy On This Page What is breast reconstruction? How do surgeons use implants to reconstruct a woman’s breast? How do surgeons ...

  1. 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. ...

  2. 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 ...

  3. 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 ...

  4. 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 ...

  5. Dual-Modality Breast Tomosynthesis1

    OpenAIRE

    Williams, Mark B.; Judy, Patricia G.; Gunn, Spencer; Majewski, Stanislaw

    2010-01-01

    Pilot clinical evaluation of this dual-modality tomosynthesis system suggests that it is a feasible and accurate method with which to detect and diagnose breast cancer and that specificity and positive predictive value can be improved by adding molecular breast imaging tomosynthesis to x-ray tomosynthesis.

  6. PET/CT and dedicated PET in breast cancer: Implications for classification, staging, and response monitoring

    NARCIS (Netherlands)

    Koolen, B.B.

    2013-01-01

    De PET-CT, een scan die gebruik maakt van radioactiviteit om tumoren in beeld te brengen, is een zinvol instrument voor beeldvorming van patiënten met borstkanker, met name van patiënten met een tumor groter dan drie centimeter of tumor-positieve lymfeklieren. De PET-CT is vooral van waarde voor de

  7. The Dedicated Aerosol Retrieval Experiment (DARE): scientific requirements for a dedicated satellite instrument to measure atmospheric aerosols

    NARCIS (Netherlands)

    Decae, R.; Courrèges-Lacoste, G.B.; Leeuw, G. de

    2004-01-01

    DARE (Dedicated Aerosol Retrieval Experiment) is a study to design an instrument for accurate remote sensing of aerosol properties from space. DARE combines useful properties of several existing instruments like TOMS, GOME, ATSR and POLDER. It has a large wavelength range, 330 to 1000 nm, to

  8. Breast cancer

    OpenAIRE

    Gablerová, Pavlína

    2010-01-01

    In this work the topic of breast cancer treated more generally and mainly focused on risk factors for the development. The theoretical part describes the general knowledge about breast cancer as a stage or treatment. The practical part is to have clarified the risk factors that have some bearing on the diagnosis of breast cancer. What level are involved in the probability of occurrence? Can we eliminate them? As a comparison of risk factors examined in the Czech Republic, England, Australia a...

  9. Engine with pulse-suppressed dedicated exhaust gas recirculation

    Science.gov (United States)

    Keating, Edward J.; Baker, Rodney E.

    2016-06-07

    An engine assembly includes an intake assembly, a spark-ignited internal combustion engine, and an exhaust assembly. The intake assembly includes a charge air cooler disposed between an exhaust gas recirculation (EGR) mixer and a backpressure valve. The charge air cooler has both an inlet and an outlet, and the back pressure valve is configured to maintain a minimum pressure difference between the inlet of the charge air cooler and an outlet of the backpressure valve. A dedicated exhaust gas recirculation system is provided in fluid communication with at least one cylinder and with the EGR mixer. The dedicated exhaust gas recirculation system is configured to route all of the exhaust gas from the at least one cylinder to the EGR mixer for recirculation back to the engine.

  10. Dedication of Stotz-Kontakt switches for Spanish utility owners

    International Nuclear Information System (INIS)

    Lopez Vergara, T.; Martin de la Torre, M.; Alminana, J.

    1996-01-01

    The Spanish Utility Owners Group commissioned Empresarios Agrupados to perform the work for the dedication of the S280 series of Stotz-KONTAKT switches and two of its possible accessories. As a results of this process, the components can be used in safety-related applications in the conditions and locations expected. This article describes the different phases of the dedication process: Technical Evaluation considering the application of switches as new or alternative elements, Acceptance Process and Purchasing Documentation. It sets out the main conclusion drawn from each phase. It also includes details of the activities performed by Empresarios Agrupados as part of the seismic qualification of components: selection of the sample to be tested, the definition of electrical tests before and after the seismic test, and the mounting, electrical powering, operating requirements and monitoring of components during seismic tests. (Author)

  11. Preliminary design of a dedicated proton therapy linac

    International Nuclear Information System (INIS)

    Hamm, R.W.; Crandall, K.R.; Potter, J.M.

    1991-01-01

    The preliminary design has been completed for a low current, compact proton linac dedicated to cancer therapy. A 3 GHz side-coupled structure accelerates the beam from a 70 MeV drift tube linac using commercially available S-band rf power systems and accelerating cavities. This significantly reduces the linac cost and allows incremental energies up to 250 MeV. The short beam pulse width and high repetition rate make the linac similar to the high energy electron linacs now used for cancer therapy, yet produce a proton flux sufficient for treatment of large tumors. The high pulse repetition rate permits raster scanning, and the small output beam size and emittance result in a compact isocentric gantry design. Such a linac will reduce the facility and operating costs for a dedicated cancer therapy system

  12. Dedicated data recording video system for Spacelab experiments

    Science.gov (United States)

    Fukuda, Toshiyuki; Tanaka, Shoji; Fujiwara, Shinji; Onozuka, Kuniharu

    1984-04-01

    A feasibility study of video tape recorder (VTR) modification to add the capability of data recording etc. was conducted. This system is an on-broad system to support Spacelab experiments as a dedicated video system and a dedicated data recording system to operate independently of the normal operation of the Orbiter, Spacelab and the other experiments. It continuously records the video image signals with the acquired data, status and operator's voice at the same time on one cassette video tape. Such things, the crews' actions, animals' behavior, microscopic views and melting materials in furnace, etc. are recorded. So, it is expected that experimenters can make a very easy and convenient analysis of the synchronized video, voice and data signals in their post flight analysis.

  13. Entraigues, a system dedicated to industrial radiography interpretation

    International Nuclear Information System (INIS)

    Fleuet, E.; Lavayssiere, B.

    1995-01-01

    Some inspections including radiography are periodically done among the components of a nuclear power plant in order to check their integrity. Today the operator is in charge of acquiring data, of analysing and of quantifying the produced X-ray films. EDF has built a digital system called ENTRAIGUES which aims to help the processing and the interpretation of radiographic images. The hardware of ENTRAIGUES is composed of a digitizer, a dedicated image processor and a PC. The software has been designed to facilitate the analysis of X-ray images. With the inclusion of compression algorithms and automatic image procedures ENTRAIGUES has become a complete tool dedicated to digitization, processing and archiving of nuclear power plant radiographs. (authors). 2 refs

  14. Cost of a dedicated ART clinic | Harling | South African Medical ...

    African Journals Online (AJOL)

    Little evidence exists on the cost of running clinics for ART provision. Objectives. To determine the cost per patient-month enrolled in an ART programme and per patient-visit for a dedicated, public-sector ART clinic in a South African peri-urban setting in 2004/05 and 2005/06, as the clinic moved from a temporary to a ...

  15. Dedicated training in adult education among otolaryngology faculty.

    Science.gov (United States)

    McMains, Kevin C; Peel, Jennifer

    2014-12-01

    Most faculty members undergo ad hoc training in education. This survey was developed to assess the prevalence and type of dedicated training in education received by academic otolaryngology-head and neck surgery (OTO-HNS) faculty in the United States. Survey. An 11-item survey was developed to assess the prevalence of dedicated instruction in education theory and practice, the types of instruction received, and the barriers to receiving instruction. The survey was sent to all OTO-HNS program directors for distribution among their respective faculty. A total of 216 responses were received. Seventy respondents (32.7%) serve as program director, associate program director, or assistant program director in their respective programs. Forty-six respondents (21.8%) had received dedicated training in education. Of the respondents who described the type of education training received, 48.7% participated in didactics/seminar, 35.9% in degree/certificate programs, 10.3% in multimodality training, and 5.1% online training. Among the barriers encountered to participation in instruction in education, time/productivity pressures was the most commonly cited reason (60.2%), followed by not knowing about the opportunity to receive training (36.4%), lack of departmental support (26.2%), lack of available training (22.3%), and the perception that such training would not be useful (7.8%). Presently, only a minority of surveyed academic otolaryngologists in the United States have received any dedicated instruction in the theory and practice of education. Personal, departmental, and institutional barriers exist in many practice environments that hinder otolaryngology faculty from participating in education training. N/A. © 2014 The American Laryngological, Rhinological and Otological Society, Inc.

  16. Quality assurance requirements for dedication process in Angra 1

    Energy Technology Data Exchange (ETDEWEB)

    Baliza, Ana Rosa, E-mail: baliza@eletronuclear.gov.br [Eletrobras Termonuclear S.A. (ELETRONUCLEAR), Angra dos Reis, RJ (Brazil). Departamento GQO.G; Morghi, Youssef, E-mail: ymo@cdtn.br [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil)

    2015-07-01

    In Brazil the regulatory body is CNEN (Comissao Nacional de Energia Nuclear), according to its requirements, when there is not a Brazilian standard, the utilities shall follow the requirements of the designer. For Angra 1, the designer is an American company - Westinghouse. So, the requirements for dedication of U.S. NRC (United States Nuclear Regulatory Commission) shall be applied, these requirements are in 10CFR21 - Reporting of Defects and Noncompliance. According to 10CFR21, when applied to nuclear power plants licensed dedication is an acceptance process undertaken to provide reasonable assurance that a commercial grade item to be used as a basic component will perform its intended safety function and, in this respect, is deemed equivalent to an item designed and manufactured under a quality assurance program standard for nuclear power plant. This assurance is achieved by identifying the critical characteristics of the item and verifying their acceptability by inspections, tests, or analyses by the purchaser or third-party dedicating entity. (author)

  17. Prospects of dedicated biodiesel engine vehicles in Malaysia and Indonesia

    International Nuclear Information System (INIS)

    Jayed, M.H.; Masjuki, H.H.; Kalam, M.A.; Mahlia, T.M.I.; Liaquat, A.M.; Husnawan, M.

    2011-01-01

    Petro diplomacy has played its role in last few decades and that makes energy security a major concern worldwide. Rapid climate change and environmental protection is another vital issue to be addressed in recent energy policies. So an alternative carbon neutral transport fuel is a must in new sustainable energy mix. Biodiesel has immense potentiality to be a part of a sustainable energy mix. In this energy scenario, Brazil's success is a role model in utilizing its agro-industry for reducing poverty, greenhouse gas emission and petro-dependency simultaneously. Brazil commercialized bioethanol in mass scale by introducing flexible fuel vehicles in market. This dedicated engine idea moralizes a new concept of dedicated biodiesel engine vehicles for Malaysia and Indonesia. Southeast Asian countries, i.e. Malaysia and Indonesia is the largest producer as well as exporter of palm oil. Growing at highest yield rate among other biodiesel feedstock, palm based biodiesel is a top exported product for this region. This paper will quantify the prospects of a dedicated biodiesel engine vehicle for Malaysia and Indonesia that will initiate palm based biodiesel in fuel supply chain by leapfrogging the barriers of biodiesel utilization by boosting local automobile industry simultaneously. This article will also review on energy scenario of Malaysia and Indonesia and their renewable energy policies and challenges for coming decades. (author)

  18. Quality assurance requirements for dedication process in Angra 1

    International Nuclear Information System (INIS)

    Baliza, Ana Rosa

    2015-01-01

    In Brazil the regulatory body is CNEN (Comissao Nacional de Energia Nuclear), according to its requirements, when there is not a Brazilian standard, the utilities shall follow the requirements of the designer. For Angra 1, the designer is an American company - Westinghouse. So, the requirements for dedication of U.S. NRC (United States Nuclear Regulatory Commission) shall be applied, these requirements are in 10CFR21 - Reporting of Defects and Noncompliance. According to 10CFR21, when applied to nuclear power plants licensed dedication is an acceptance process undertaken to provide reasonable assurance that a commercial grade item to be used as a basic component will perform its intended safety function and, in this respect, is deemed equivalent to an item designed and manufactured under a quality assurance program standard for nuclear power plant. This assurance is achieved by identifying the critical characteristics of the item and verifying their acceptability by inspections, tests, or analyses by the purchaser or third-party dedicating entity. (author)

  19. Methodology for creating dedicated machine and algorithm on sunflower counting

    Science.gov (United States)

    Muracciole, Vincent; Plainchault, Patrick; Mannino, Maria-Rosaria; Bertrand, Dominique; Vigouroux, Bertrand

    2007-09-01

    In order to sell grain lots in European countries, seed industries need a government certification. This certification requests purity testing, seed counting in order to quantify specified seed species and other impurities in lots, and germination testing. These analyses are carried out within the framework of international trade according to the methods of the International Seed Testing Association. Presently these different analyses are still achieved manually by skilled operators. Previous works have already shown that seeds can be characterized by around 110 visual features (morphology, colour, texture), and thus have presented several identification algorithms. Until now, most of the works in this domain are computer based. The approach presented in this article is based on the design of dedicated electronic vision machine aimed to identify and sort seeds. This machine is composed of a FPGA (Field Programmable Gate Array), a DSP (Digital Signal Processor) and a PC bearing the GUI (Human Machine Interface) of the system. Its operation relies on the stroboscopic image acquisition of a seed falling in front of a camera. A first machine was designed according to this approach, in order to simulate all the vision chain (image acquisition, feature extraction, identification) under the Matlab environment. In order to perform this task into dedicated hardware, all these algorithms were developed without the use of the Matlab toolbox. The objective of this article is to present a design methodology for a special purpose identification algorithm based on distance between groups into dedicated hardware machine for seed counting.

  20. Survey VS audit by using method 2 to dedicate commercial grade services

    International Nuclear Information System (INIS)

    Martinez ayucar, F. J.

    2014-01-01

    Since the start of the commercial grade dedications, both 10CFR21 and EPRI documents, plus the dedication of commercial grade components, and the stage of commercial grade dedication of the services contemplated. And recently the NRC through various communications and answers trafficking among other issues the commercial grade dedication service. The NRC has detected repeatedly incorrect application of the survey as a method of commercial grade dedication and instead has done an audit of the program elements of commercial quality. (Author)

  1. Dedicated researcher brings cancer care to rural communities

    Directory of Open Access Journals (Sweden)

    Sharan Bhuller

    2016-10-01

    that lack reliable clean water or electricity. It is an incredibly cost-effective option for low-resource countries seeking to develop national cervical cancer screening and treatment programs according to PATH.“Both projects were completed successfully and brought out research conclusions in the form of national and international publications,” Dr. Asthana says. In addition to the projects, she had also developed health education materials to create cervical cancer awareness among the women of rural Indian community, while providing training to auxiliary nurses and midwives for cervical cancer screening.Dr. Asthana graduated with a degree in Bachelor of Medicine and Bachelor of Surgery from King George Medical College (KGMC, Lucknow, Uttar Pradesh, India, before pursuing her Doctor of Medicine (MD in Community Medicine from Ganesh Shankar Vidyarthi Memorial (GSVM Medical College, Kanpur, India.  Throughout her career, she has published over 40 articles in national and international journals. As a result of her hard work and dedication toward the medical field, she has been awarded first prizes for oral presentation in international conferences such as Indian Cancer Congress (ICC 2014 and Asia Oceania Research Organisation on Genital Infections and Neoplasia (AOGIN 2012.She is an active member of various scientific associations and societies such as the Indian Association for Cancer Research (IACR, Indian Society for Medical Statistics (ISMS, Indian Association of Preventive and Social Medicine (IAPSM, and International Epidemiological Association (IEA. In her effort to provide impactful messages via research publications, she is currently working on remodeling the cancer registry data, which includes a diversified field for incidence of childhood cancer, breast and cervical cancer, trends of major cancer, cancer burden in Northeast of India, among other things.According to Dr. Asthana, her vision is the utilization of voluminous cancer registry data to produce

  2. Breast asymmetry and predisposition to breast cancer

    OpenAIRE

    Scutt, Diane; Lancaster, Gillian A; Manning, John T

    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 ...

  3. MOLECULAR BASIS OF EPIDERMAL GROWTH FACTOR RECEPTOR AND CYCLIN E EXPRESSION INTERDEPENDENCE IN BASAL-LIKE SUBTYPE OF INVASIVE BREAST CARCINOMA.

    Science.gov (United States)

    Mariamidze, A; Gogiashvili, L; Khardzeishvili, O; Javakhishvili, T; Makaridze, D

    2018-03-01

    Aim of the study was the simultaneous assessment of EGFR and Cyclin E in "basal-like" carcinoma group, in order to establish their interactivity in the aspect of the age and grade of the tumor, taking into account the common parallel HER2+ samples. The study involved postoperative and/or biopsy material (paraffin blocks) of 237 patients from archived data, who were operated due to breast cancer (National Cancer Center of Tbilisi, 2008-2012 years). In TNBC group and "basal-like" tumor subgroup expression of ESFR, Cyclin E and Cytokeratins 5/6 and 17 were shown advanced activity of processes and high dependence to patients age. Taking into account all above mentioned, the immunohistochemical profile of "basal-like" type of breast cancer is defined mostly by sensitivity to cytokeratins CK5,6/17 and EGFR. In addition, the defected synthesis and activity of the latter, which is actually observed in "basal-like" carcinoma, leads to increased malignancy grade and mitotic activity, which creates the phenotypic and group characteristics for this type of carcinomas overall.

  4. Detection of high frequency of mutations in a breast and/or ovarian cancer cohort: implications of embracing a multi-gene panel in molecular diagnosis in India.

    Science.gov (United States)

    Mannan, Ashraf U; Singh, Jaya; Lakshmikeshava, Ravikiran; Thota, Nishita; Singh, Suhasini; Sowmya, T S; Mishra, Avshesh; Sinha, Aditi; Deshwal, Shivani; Soni, Megha R; Chandrasekar, Anbukayalvizhi; Ramesh, Bhargavi; Ramamurthy, Bharat; Padhi, Shila; Manek, Payal; Ramalingam, Ravi; Kapoor, Suman; Ghosh, Mithua; Sankaran, Satish; Ghosh, Arunabha; Veeramachaneni, Vamsi; Ramamoorthy, Preveen; Hariharan, Ramesh; Subramanian, Kalyanasundaram

    2016-06-01

    Breast and/or ovarian cancer (BOC) are among the most frequently diagnosed forms of hereditary cancers and leading cause of death in India. This emphasizes on the need for a cost-effective method for early detection of these cancers. We sequenced 141 unrelated patients and families with BOC using the TruSight Cancer panel, which includes 13 genes strongly associated with risk of inherited BOC. Multi-gene sequencing was done on the Illumina MiSeq platform. Genetic variations were identified using the Strand NGS software and interpreted using the StrandOmics platform. We were able to detect pathogenic mutations in 51 (36.2%) cases, out of which 19 were novel mutations. When we considered familial breast cancer cases only, the detection rate increased to 52%. When cases were stratified based on age of diagnosis into three categories, ⩽40 years, 40-50 years and >50 years, the detection rates were higher in the first two categories (44.4% and 53.4%, respectively) as compared with the third category, in which it was 26.9%. Our study suggests that next-generation sequencing-based multi-gene panels increase the sensitivity of mutation detection and help in identifying patients with a high risk of developing cancer as compared with sequential tests of individual genes.

  5. Breast cancer

    International Nuclear Information System (INIS)

    Tokunaga, Masayoshi

    1992-01-01

    More than 20-year follow-up of A-bomb survivors in Hiroshima and Nagasaki has a crucial role in determining the relationship of radiation to the occurrence of breast cancer. In 1967, Wanebo et al have first reported 27 cases of breast cancer during the period 1950-1966 among the Adult Health Study population of A-bomb survivors. Since then, follow-up surveys for breast cancer have been made using the Life Span Study (LSS) cohort, and the incidence of breast cancer has increased year by year; that is breast cancer was identified in 231 cases by the first LSS series (1950-1969), 360 cases by the second LSS series (1950-1974), 564 cases by the third LSS series (1950-1980), and 816 cases in the fourth LSS series (1950-1085). The third LSS series have revealed a high risk for radiation-induced breast cancer in women aged 10 or less at the time of exposure (ATE). Both relative and absolute risks are found to be decreased with increasing ages ATE. Based on the above-mentioned findings and other studies on persons exposed medical radiation, radiation-induced breast cancer is characterized by the following: (1) the incidence of breast cancer is linearly increased with increasing radiation doses; (2) both relative and absolute risks for breast cancer are high in younger persons ATE; (3) age distribution of breast cancer in proximally exposed A-bomb survivors is the same as that in both distally A-bomb survivors and non-exposed persons, and there is no difference in histology between the former and latter groups. Thus, immature mammary gland cells before the age of puberty are found to be most radiosensitive. (N.K.)

  6. Technical validation of an RT-qPCR in vitro diagnostic test system for the determination of breast cancer molecular subtypes by quantification of ERBB2, ESR1, PGR and MKI67 mRNA levels from formalin-fixed paraffin-embedded breast tumor specimens.

    Science.gov (United States)

    Laible, Mark; Schlombs, Kornelia; Kaiser, Katharina; Veltrup, Elke; Herlein, Stefanie; Lakis, Sotiris; Stöhr, Robert; Eidt, Sebastian; Hartmann, Arndt; Wirtz, Ralph M; Sahin, Ugur

    2016-07-07

    MammaTyper is a novel CE-marked in vitro diagnostic RT-qPCR assay which assigns routinely processed breast cancer specimens into the molecular subtypes Luminal A-like, Luminal B-like (HER2 positive or negative), HER2 positive (non-luminal) and Triple negative (ductal) according to the mRNA expression of ERBB2, ESR1, PGR and MKI67 and the St Gallen consensus surrogate clinical definition. Until now and regarding formalin-fixed, paraffin-embedded material (FFPE), this has been a task mostly accomplished by immunohistochemistry (IHC). However the discrepancy rates of IHC for the four breast cancer biomarkers are frequently under debate, especially for Ki-67 which carries the highest degree of inter- and even intra-observer variability. Herein we describe a series of studies in FFPE specimens which aim to fully validate the analytical performance of the MammaTyper assay, including the site to site reproducibility of the individual marker measurements. Tumor RNA was extracted with the novel RNXtract RNA extraction kit. Synthetic RNA was used to assess the sensitivity of the RNXtract kit. DNA and RNA specific qPCR assays were used so as to determine analyte specificity of RNXtract. For the assessment of limit of blank, limit of detection, analytical measurement range and PCR efficiency of the MammaTyper kit serial dilutions of samples were used. Analytical precision studies of MammaTyper were built around two different real time PCR platforms and involved breast tumor samples belonging to different subtypes analyzed across multiple sites and under various stipulated conditions. The MammaTyper assay robustness was tested against RNA input variations, alternative extraction methods and tumor cell content. Individual assays were linear up to at least 32.33 and 33.56 Cqs (quantification cycles) for the two qPCR platforms tested. PCR efficiency ranged from 99 to 109 %. In qPCR platform 1, estimates for assay specific inter-site standard deviations (SD) were between 0.14 and

  7. Technical validation of an RT-qPCR in vitro diagnostic test system for the determination of breast cancer molecular subtypes by quantification of ERBB2, ESR1, PGR and MKI67 mRNA levels from formalin-fixed paraffin-embedded breast tumor specimens

    International Nuclear Information System (INIS)

    Laible, Mark; Schlombs, Kornelia; Kaiser, Katharina; Veltrup, Elke; Herlein, Stefanie; Lakis, Sotiris; Stöhr, Robert; Eidt, Sebastian; Hartmann, Arndt; Wirtz, Ralph M.; Sahin, Ugur

    2016-01-01

    MammaTyper is a novel CE-marked in vitro diagnostic RT-qPCR assay which assigns routinely processed breast cancer specimens into the molecular subtypes Luminal A-like, Luminal B-like (HER2 positive or negative), HER2 positive (non-luminal) and Triple negative (ductal) according to the mRNA expression of ERBB2, ESR1, PGR and MKI67 and the St Gallen consensus surrogate clinical definition. Until now and regarding formalin-fixed, paraffin-embedded material (FFPE), this has been a task mostly accomplished by immunohistochemistry (IHC). However the discrepancy rates of IHC for the four breast cancer biomarkers are frequently under debate, especially for Ki-67 which carries the highest degree of inter- and even intra-observer variability. Herein we describe a series of studies in FFPE specimens which aim to fully validate the analytical performance of the MammaTyper assay, including the site to site reproducibility of the individual marker measurements. Tumor RNA was extracted with the novel RNXtract RNA extraction kit. Synthetic RNA was used to assess the sensitivity of the RNXtract kit. DNA and RNA specific qPCR assays were used so as to determine analyte specificity of RNXtract. For the assessment of limit of blank, limit of detection, analytical measurement range and PCR efficiency of the MammaTyper kit serial dilutions of samples were used. Analytical precision studies of MammaTyper were built around two different real time PCR platforms and involved breast tumor samples belonging to different subtypes analyzed across multiple sites and under various stipulated conditions. The MammaTyper assay robustness was tested against RNA input variations, alternative extraction methods and tumor cell content. Individual assays were linear up to at least 32.33 and 33.56 Cqs (quantification cycles) for the two qPCR platforms tested. PCR efficiency ranged from 99 to 109 %. In qPCR platform 1, estimates for assay specific inter-site standard deviations (SD) were between 0.14 and 0

  8. The role of general nuclear medicine in breast cancer

    International Nuclear Information System (INIS)

    Greene, Lacey R; Wilkinson, Deborah

    2015-01-01

    The rising incidence of breast cancer worldwide has prompted many improvements to current care. Routine nuclear medicine is a major contributor to a full gamut of clinical studies such as early lesion detection and stratification; guiding, monitoring, and predicting response to therapy; and monitoring progression, recurrence or metastases. Developments in instrumentation such as the high-resolution dedicated breast device coupled with the diagnostic versatility of conventional cameras have reinserted nuclear medicine as a valuable tool in the broader clinical setting. This review outlines the role of general nuclear medicine, concluding that targeted radiopharmaceuticals and versatile instrumentation position nuclear medicine as a powerful modality for patients with breast cancer

  9. New Developments in Breast Cancer Screening and Treatment.

    Science.gov (United States)

    Tilstra, Sarah; McNeil, Melissa

    2017-01-01

    The clinical update serves as a brief review of recently published, high-impact, and potentially practice-changing journal articles summarized for our readers. In this clinical update, we selected top recent articles regarding breast health that may change the clinical practice of women's health providers. We identified articles by reviewing high-impact medical and women's health journals as well as national practice guidelines. Three of our articles are dedicated to the rapid changes in breast cancer screening. With regard to breast cancer treatment, we focused on two articles that impact who we treat with traditional aggressive regimens.