bluuebunny/crossref_metadata_2025_split huggingface dataset:
First clinical experience of contrast enhanced digital mammography (CEDM) for the detection of breast carcinomas.
Authors: Dromain C , Balleyguier C , Tardivon A , Rimareix F , Delaloge S 
Published: December 2010

Abstract
Abstract #5001
Purpose: CEDM is a recent development of digital mammography using the intra-venous injection of an iodinated contrast agent in conjunction with a mammography examination. The objective of this paper is to present two techniques developed to perform CEDM examinations, the preliminary clinical experiences and potential clinical applications of this new breast imaging procedure.&#x2028; Material and methods: Between 2005 and 2008, 140 consenting women with suspicious findings on mammography and or ultrasonography underwent CEDM using modified full-field digital mammography systems (GE Healthcare, Chalfont St-Giles, UK). A temporal subtraction sequence with acquisition of high-energy images before and after contrast medium injection was used for the first 20 patients. A dual energy technique with acquisition of a pair of low and high-energy images only after contrast medium injection was used for the other 120 patients.&#x2028; Results: CEDM, either using temporal or dual energy technique, improved the probability of malignancy and the BIRADS assessment compared to conventional mammography alone. The temporal subtraction technique offered the possibility to analyze the kinetic curve of enhancement of breast lesions, similar to breast MRI. Dual energy technique did not provide information about the kinetic of tumor enhancement but allowed the acquisition of multiples views of the same breast or bilateral examination and was less sensitive to patient motion than temporal CEDM. The potential clinical applications are the determination of the extent of disease, the assessment of recurrent disease, the clarification of mammographically equivocal lesions, the detection of occult lesions on standard mammography, particularly in dense breast, and the monitoring of the response to chemotherapy.&#x2028; &#x2028; &#x2028; &#x2028; Conclusion: Initial clinical experience has shown the ability of CEDM to map the distribution of neovasculature induced by cancer using mammography. CEDM should result in a simple way to enhance the detection and the characterization of breast lesions and to provide some prognostic factors of breast carcinomas.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5001.
A potential serum panel for breast cancer diagnosis: ongoing clinical validation for its clinical implication.
Authors: Lee J , Kim B , Han W , Ko E , Kim E , Hwang K , Kim S , Park P , Kim C , Noh D 
Published: December 2010

Abstract
Abstract #5006
Although every effort has been made to discover single potent biomarkers in oncology, the promising single biomarker often loses its clinical potency in the course of clinical validations. We aimed to construct and verify a biomarker panel with multiple proteins for breast cancer diagnosis. Using Surface-Enhanced Laser Desorption/ Ionization Time-of-Flight mass spectrometry (SELDI-TOF-MS) and microbead array system, epidermal growth factor (EGF), vascular cell adhesion molecule-1 (VCAM-1), CD40L, vitronectin, plasminogen activation inhibitor-1 (PAI-1), vitamin-D binding protein (VDBP), C-reactive protein (CRP), kininogen, apolipoprotein A1 and proapolipoprotein A1 were identified and validated as useful biomarkers for detection of breast cancer. The multiplexing panel (MP) which was constructed by combining algorithm (random forest, support vector machine) with above biomarkers showed that the diagnostic accuracy approached 91% in 216 test samples. A following double blind test verified that the diagnostic accuracy of the MP was 68% with an additional validation set including sera from 49 patients with breast cancer and 51 healthy women (sensitivity=74%; 95% confidence interval (CI)=58.9–85.0%, specificity=62.7%; 95% CI=48.1–75.9%, positive predictive value=65.5%; 95% CI=55.7-75.3%, negative predictive value=71.7%; 95% CI=61.7-80.35%). We suggest that these results support the potential use of the MP as an early detector of breast cancer. In order to validate the role and potency of the MP in routine clinical practice, a large scale clinical validation in a cohort consisting of 500 patients with breast cancer and the same number of healthy women are underway and the results will be released in the near future.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5006.
Detecting BRCA2 protein truncation in breast tissue biopsies to identify hereditary cancer.
Authors: Lieberman R , Snyder C , Clark V , Lynch H , Holt J 
Published: December 2010

Abstract
Abstract #501
Background: Mutations in the BRCA2 gene are dominantly inherited but cause cancers when the wildtype allele has LOH (loss of heterozygosity) within the cancer. It is important to identify breast cancer patients with BRCA mutations so they can be appropriately treated and affected family members can implement cancer prevention strategies. Because most disease-associated BRCA2 mutations are truncating mutations, a test for truncated BRCA2 proteins should identify most BRCA2 hereditary cancers. Methods: We have developed a tissue truncation test to identify truncated BRCA2 proteins in breast cancer tissue biopsies by direct immunohistochemistry, without amplification or genetic manipulations. N-terminal and C-terminal antibodies are used to visualize protein truncation by demonstrating that the beginning of the protein is present but the end (terminus) is absent. Results: A quantitative C-terminal immunostaining score or a C/N terminal truncation ratio correctly classified 20/21 breast cancers from BRCA2 mutation carriers and 57/58 sporadic breast cancers. This represents a sensitivity of 95% and specificity of 98%. Figure 1 shows a loss of C-terminal staining (except for a lymphocyte) in the upper panel but strong N-terminal staining in the lower panel sections of the same hereditary breast cancer.&#x2028; &#x2028; Due to the presence of C-terminal BRCA2 protein and atypical clinical features of the misclassifed cancer in a BRCA2 mutation carrier,we performed PCR and sequence analyses on this cancer. The results showed continued presence of the BRCA2 wildtype allele in the cancer, indicating that this represents a sporadic cancer which occurred in a mutation carrier. Conclusions: This immunohistochemistry based test (which takes only 4 hours) appears to identify BRCA2 hereditary cancer with high accuracy. The test also appears to diagnose the biochemical loss of BRCA2 protein in cancers (BRCA2 mutant genotype) which will usually but not always agree with the presence of a germline BRCA2 mutation found by susceptibility testing by DNA sequencing of blood samples. This rapid but accurate tissue test can diagnose hereditary BRCA2 breast cancer at time of biopsy, allowing medical oncologists to implement targeted therapies and surgeons to perform timely prophylactic surgery without the usual 4 week wait for DNA sequencing results.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 501.
Evolution of breast cancer screening in France from 2005 to 2008: results of the EDIFICE survey.
Authors: Pivot X , Coscas Y , Morere J , Namer M , Blay J , Roussel C , Eisinger F 
Published: December 2010

Abstract
Abstract #5010
Background: In 2005, a first EDIFICE survey was aimed to provide a better understanding of population s adherence to the screening tests available in France and results pertaining to breast cancer are reported (Int. J. Med. Sci. 2008, 5: 106-112). In 2008, EDIFICE survey is performed again to assess the evolution 3 years later. Taking into account that the Implementation of breast cancer screening has been generalized in France since 2003: All women aged between 50 and 74 years are systematically invited to perform a mammography every two years.&#x2028; Methods: This second nationwide observational survey was carried out from December 12, 2007 to January 07, 2008 among a representative samples of 1802 French people aged between 40 and 85 years and 600 general practitioners (GPs). Information collected included socio-demographic characteristics, attitude towards cancer screening and actual experience of cancer screening, as well as GPs practice regarding screening. The precision of the results is 4.3% for a 95% confidence interval.&#x2028; Results: In EDIFICE–1 and -2, 501 and 488 participating women aged between 50 and 74 years are assessed, respectively.&#x2028; &#x2028; In EDIFICE-2, there was a significant relationship (p&lt;0.05) between the existence of a first mammography screening on women s own initiative and age (odd ratio 0.35; 95%CI 0.13 – 0.95). Main factors associated with performing the screening test every two years were: knowledge of screening process (odd ratio 3.59 ; 95%CI 1.54 – 8.38), Own motivation (odd ratio 5.03; 95%CI 1.6 – 15.8), First mammography performed in the organized screening (odd ratio 6.53 ; 95%CI 1.15 – 37.3), and gynecologist consultation (odd ratio 8.68; 95%CI 2.21 – 34.11).&#x2028; Of the 600 participating GPs, 68% systematically recommended a mammography to their patients in the screening national plan. GPs perceptions of the reasons for women s avoidance of the screening test were unwillingness to be aware of mammography results (46%) and négligence (24%).&#x2028; Conclusion: The main result of this second EDIFICE Survey is to stress the impact of the breast cancer screening in France. Between 2005 and 2008 the rate of women s attendance at mammography screening has increased and the proportion of women who repeat the test every two years has been dramaticaly improve.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5010.
Improving community access for breast cancer screening.
Authors: Bell JL , Gray KD , Huggler PZ 
Published: December 2010

Abstract
Abstract #5016
Background: The Breast Health Outreach Program (BHOP) at the University of Tennessee Medical Center's Cancer Institute began in 1996 delivery breast health education and mobile mammography to underserved areas in East Tennessee. Through grant funding, dedicated personnel and community support, the program is able to provide breast health services to 25 East Tennessee counties.&#x2028; Study Design: The BHOP is designed to deliver culturally and educationally sensitive breast health education classes prior to onsite mobile mammography screening. Thirty-minute classes inform women of appropriate, best breast health practices, eliminate fears associated with mammography and encourage women to obtain annual screening. Once relationships are established, the BHOP is offered annually in churches, industrial work sites, and community centers.&#x2028; &#x2028; Results: Since 1996, the BHOP has educated over 13,500 women, delivered approximately 8,800 screening mammograms and diagnosed 20 cancers. As delivery processes improved, 6,851 screening mammograms were provided between 2002 and 2006 with 1,080 women receiving their first-ever mammogram. Fourteen breast cancers were diagnosed in this period. Further data analysis from this time period reveals increases in education, screenings, first-ever mammograms and diagnosed cancers.&#x2028; Conclusions: Mobile mammography is becoming "standard" in rural communities of East Tennessee. Most of the women now participating in the program have had previous mammograms through the BHOP. Each year the BHOP has increased the number of women obtaining their first-ever mammogram by targeting new sites. Companies and communities are moving to support healthy living practices and providing healthier environments for employees and their families. As the BHOP has matured and become widely recognized, measures of program effectiveness have improved. Future areas for research will address longitudinal data tracking to assess mortality impact and early diagnosis trends.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5016.
Characterization of the HER2 status on circulating breast cancer cells.
Authors: Alix-Panabières C , Riethdorf S , Fehm T , Vendrell J , Pantel K 
Published: December 2010

Abstract
Abstract #5018
Background: Detection and characterization of circulating tumor cells (CTC) in the peripheral blood of breast cancer patients could help to guide treatment decisions before the onset of overt metastasis as well as in the setting of advanced disease. The HER2 oncogene is the most prominent therapeutic target in breast cancer and shedding of the extracellular domain of this receptor seems to contribute to constitutive activation of HER2. Here we developed a novel assay to detect shedding of the extracellular domain (ECD) of the HER2 oncogene on single CTC and applied this assay to the analysis of blood from metastatic breast cancer patients.&#x2028; Material and Methods: Using a new dual fluorescent CK19/HER2-EPISPOT assay, the shedding of HER2 ECD by CTC from 49 metastatic breast cancer patients was assessed. In parallel, using the CellSearch system, the number of CTC and their HER2 expression were determined on 42 samples from metastatic breast cancer patients. A subgroup (n=34) of these patients was analyzed with both methods. This work was performed in the context of the activities of the DETECT study group.&#x2028; Results: In the CK19/HER2-EPISPOT assay 24 of 49 (48.9%) patients had CTC (mean, 12.4; median, 5; range 1-141) and among these positive patients, 7 of 24 (29.2%) showed also HER2-secreting CTC (mean, 3.3; median, 2; range, 1-14). Using the CellSearch™ system, in 23/42 (54.8%) patients CTC were found (mean, 82; median, 13; range, 1-656). HER2 staining intensity was heterogeneous even among CTC from the same patient. Regarding the samples analyzed with both methods, we found that 23.5%, 50.0%, 50.0% and 76.5% of the patients were positive with both detection methods, the EPISPOT assay only, the CellSearch™ system only and one or the other method, respectively.&#x2028; Discussion: These findings demonstrate, for the first time, that (i) CTC can secrete HER2 and (ii) HER2 secretion is not closely linked to HER2 CellSearch™ status. Both assays (i.e., EPISPOT and CellSearch™) have a comparative sensitivity and appear to be complementary for the detection and characterization of the HER2-status of CTC.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5018.
HER-2 expression on circulating tumor cells in metastatic breast cancer.
Authors: Hayashi N , Yagata H , Hamaoka T , Sarumaru S , Tsugawa K , Yoshida A , Tsunoda-Shimizu H , Suzuki K , Shimada M , Shimoda Y , Nakamura S 
Published: December 2010

Abstract
Abstract #5020
Background: HER-2 Overexpression in breast cancer is associated with poor prognosis. The circulating tumor cells (CTCs) in peripheral blood can be identified in patients with breast cancer. They are recognized as a predictor of the effect of systemic therapy, and also as a prognostic marker recently. Cristofanilli et al reported that progression-free Survival (PFS) and overall survival(OS) in metastatic breast cancer patients with &lt;5CTCs per7.5ml are significantly better than those with &gt;5CTCs before initiation of a new line of therapy and at the 1st follow-up visit. However, the detection rate and value of HER-2 Overexpression on CTCs has been not determined well.Materials and Methods:CTCs were obtained prospectively for 22 patients with metastatic breast cancer to start a new line of treatment at single institution. Blood specimens were collected at monthly intervals for a period of up to 12 weeks. CT scans were also performed before start of the treatment and 12 weeks after. HER-2 expression on primary lesions and CTCs were determined by both immunohistochemical methods and fluorescence in situ hybridization (FISH) analysis. Mean age was 54.4 years (range, 32-75 years). 8 patients received first line therapy, one patient received second line therapy, and 13 patients received over third line therapy. Of the 22 primary cancer, 7(31.8%) were HER-2 positive(score,+3 or +2/FISH positive) and 15 (68.2%) were HER-2 negative. CTCs were determined using Cell Search™ System.Results:14(63.6%) patients had clinical benefit (partial response and stable disease) during the course. CTCs were detected in 16 patients (72.7%). OS for patients with &lt;5CTCs were significantly longer than those with 5&lt; at any period. In 15 patients with HER-2 negative primary cancer, 5 patients (33.3%) were with HER-2 positive CTCs. However, in 7 patients with HER-2 positive primary cancer, 6 patients (85.7%) who had been treated with trastuzumab was with HER-2 negative CTCs. But only one patient (14.3%) treated without trastuzumab was with HER-2 positive CTCs. The patient had been treated with trastuzumab and failed in past. And the median OS time for those patients with HER2 Positive CTCs were significantly shorter (130.5 days) than for those patients with HER2 negative CTCs (283.3 days). Surprisingly, 5 (83.3%) of 6 patients with HER-2 positive CTCs were dead within 7 months.Conclusion:The number of CTCs is a prognostic marker for the patients with metastatic breast cancer. Furthermore, HER-2 positive CTCs is much related to poor prognosis. And these results indicated that the possibility of negative conversion of HER2 expression on CTCs for patients with HER-2 positive primary cancer due to trastuzumab. Trastuzumab may be effective for the patients with HER2 negative primary cancer and HER-2 positive CTCs.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5020.
Multicenter study on the detection of disseminated tumor cells in primary breast cancer.
Authors: Effenberger KE , Borgen E , Christine EE , Andrea G , Marit S , Kaaresen R , Jahn NM , Pantel K , Bjorn N 
Published: December 2010

Abstract
Abstract #5021
Background: Detection of disseminated tumor cells (DTC) in bone marrow (BM) has prognostic value in primary breast cancer (BC) and is currently under investigation for therapy stratification and monitoring. Anti-cytokeratin (CK) antibodies (Abs) have been established as markers for detection of such DTC in patients with BC. Here we present a direct comparison of the two Abs most frequently used for DTC detection over the past 10 years.&#x2028; Material and Methods: We screened BM samples from 391 BC patients of which 64 were node-positive (N+). All patients were free of any signs of overt metastases (stage M0, pT1-3, pN0-3). Tumor cells in BM were enriched by Ficoll-Hypaque gradient and the mononuclear cell (MNC) fraction was spun on slides. For each patient 2*106 MNC were analyzed per Ab, using A45-B/B3 (A45) and AE1/AE3 (AE) Abs in parallel. A45 staining was, however, performed a couple of years later than AE staining, on cytospins stored at -80°C. All samples were screened automatically for the presence of CK-positive cells. By morphological evaluation only TC-compatible cells were scored positive. Median follow-up times ranged from 5 to 118 months.&#x2028; Results: For both Abs, the number of DTC revealed was 5 or less. Of the 391 patients, 24 patients (6.1%) were positive for A45, and 41 patients (10.5%) for AE, respectively. Concordance obtained by cross-analysis for the two Abs was 84.4%, whereas the overlap in positive cases was only 3.2%. Regarding immunohistopathological characteristics AE- and A45-positive BM were found significantly more frequent in tumors of higher nodal status (p=0.003 and p=0.026), and for AE also in hormone receptor negative (HR-) compared to HR+ patients (p=0.006). Positivity for AE and/or A45 staining in BM correlated with high nodal status and large tumor size (p=0.001 and p= 0.016, respectively). Survival analyses revealed shorter relapse-free survival for A45-positive patients (p=0.026). In node-positive patients, a significantly worse prognosis regarding overall and BC specific survival was observed for AE-positive (p=0.0245 and p=0.0125) and for AE- and/or A45-positive patients (p=0.035 and p=0.044, respectively). In node-negative patients, A45-positivity was correlated to a significantly shorter relapse-free survival (p=0.032). Immunocytochemical double staining of BM samples from 26 patients (M+ and M0) revealed subpopulations of DTC labeled with both Abs (in 8/26 cases) and other DTC exclusively stained for either A45 or AE (4/26).&#x2028; Discussion: Our results indicate that the two anti-cytokeratin Abs most frequently used for DTC detection in BM do not give identical results. They appear to identify at least partially different subpopulations of DTC in BC patients. This implies a possible advantage of the combined use of these Abs in future trials using DTC diagnostics.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5021.
Circulating tumour cell (CTC) detection: a direct comparison between the CellSearch system, the AdnaTest, CK19/MAM RT-PCR and unmethylated/methylated free DNA in patients with metastatic breast cancer.
Authors: Van Der Auwera I , Elst H , Benoy I , Prové A , Wuyts H , Maes H , Van Dam P , Huget P , Vermeulen P , Dirix L 
Published: December 2010

Abstract
Abstract #5025
Introduction: The detection, enumeration and isolation of CTC has considerable potential to influence the clinical management of patients with breast cancer. There is however a substantial variability in the rates of positive samples using existing detection techniques. This study was designed to compare the sensitivities and specificities of three techniques for detecting CTC in blood of patients with metastatic breast cancer (MBC). Furthermore, correlations between CTC and circulating total and tumor-related methylated DNA were investigated.&#x2028; Material and Methods: The presence of CTC in blood samples of 80 patients with MBC and 20 healthy controls was assessed by two commercial systems: i) the CellSearch System (Veridex LLC, Warren, NJ), in which epithelial cells are immunomagnetically separated and fluorescently labeled, and nucleated (DAPI+) cells with the EpCAM+, cytokeratin (CK) 8/18/19+, and CD45- phenotype are counted as CTC and ii) the AdnaTest and a real-time qRT-PCR assay for the detection of CK-19 and mammaglobin (MAM) transcripts. Plasma total DNA levels were measured by a qPCR method. Sera were analyzed by methylation-specific qPCR for three methylated markers: APC, RASSF1A and ESR1. The results obtained with AdnaTest are being analyzed and will be presented at the meeting.&#x2028; Results: Numbers of CTC identified by the CellSearch test were significantly higher in blood samples of patients with MBC than in healthy controls: the median number of CTC detected in 7.5 ml of blood was 1 (range 0-2617) in patients with MBC and 0 (range 0-1) in controls (P&lt;0.001). Using ≥2 cells as a threshold for positivity, which corresponds to 100% specificity in the control population, 34% of samples from patients with MBC were positive with the CellSearch test. Using a cut-off to ensure 100% specificity in the control population, 31% of patients were positive for CK-19, 49% for MAM and 61% for CK-19 and/or MAM by qRT-PCR. When the CellSearch test and the qRT-PCR for CK-19 and MAM were compared, the concordance was 57%. Positive samples with the CellSearch test, but not with the qRT-PCR assay, also showed significantly higher levels of circulating total DNA and were more likely to be positive for one of the methylated DNA markers in serum.&#x2028; Conclusion : We observed a substantial variation in the detection rates of CTC in blood from breast cancer patients using different techniques. A higher rate of positive samples was observed using a combined qRT-PCR approach for CK-19 and MAM, which suggests that this is currently the most sensitive technique for detecting CTC.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5025.