bluuebunny/crossref_metadata_2025_split huggingface dataset:
DNA Methylation – Role in Gene Regulation and Detection Methods.
Authors: Sukumar S. 
Published: December 2010

Abstract
Alteration in the epigenome, which includes DNA methylation, is by far, the most frequent cancer-specific event, and likely one of the earliest in the process of carcinogenesis. Human tumors display global hypomethylation, but selective hypermethylation occurs in the promoters of growth and tumor suppressor genes, which leads to subsequent silencing of gene expression. In addition to protein coding genes, this epigenetic control is exercised in the case of microRNAs as well. DNA methylation acts in concert with histone modifications to achieve an open or closed chromatin conformation that is conducive to gene transcription or silencing respectively. Methylation of DNA takes place at cytosine residues of CpG dinucleotides. When it occurs at multiple CpG dinucleotides (CpG islands) present in the promoter region of the gene, silencing of gene expression can ensue. The current state of knowledge regarding the components of this complex but reversible machinery will be discussed. Tumor specific methylation of genes and microRNAs has been reported in all types of liquid and solid tumors. Thus, tumor specific gene methylation has provided an embarrassment of riches as potential markers for risk assessment, early detection, predictive markers for drug susceptibility, and for predicting response to therapy. The ability to pharmacologically reverse epigenetic silencing of gene expression has resulted in the identification of number of drugs with great potential for treating all types of cancers. How does one detect methylation in DNA? The study of DNA methylation was revolutionized by the development of PCR and methods that rely on base changes brought about by treatment of DNA with sodium bisulfite. Recently, other methods have relied on separation of DNA using antibodies that recognize methylated DNA. These analyses are performed on a selected panel of genes or aim to determine the global methylation profile of a specific subset of cells in a tissue. A major challenge in the clinic is the application of these methods to very small clinical samples such as single biopsy sections, or microliters of body fluids while retaining a high level of sensitivity and specificity. These methods will be discussed, presenting advantages and disadvantages of each.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr ES4-1.
Diagnostic and Therapeutic Applications of Nanotechnology.
Authors: West J. 
Published: December 2010

Abstract
The increasing capability to manipulate matter at the nanoscale is generating new materials with unique properties that promise to address unmet medical needs for future generations. As an example, metal nanoshells are a relatively new class of nanoparticles with highly tunable optical properties. Metal nanoshells consist of a dielectric core nanoparticle such as silica surrounded by an ultrathin metal shell, usually composed of gold for biomedical applications. Depending on the size and composition of each layer of the nanoshell, particles can be designed to either absorb or scatter light over much of the visible and infrared regions of the electromagnetic spectrum, including the near infrared region where penetration of light through tissue is maximal. These particles are also easily conjugated to antibodies and other biomolecules for specific targeting. Further, the biocompatibility of these particles is excellent. One can envision a myriad of potential applications of such tunable particles. Several potential biomedical applications are under development, including immunoassays, modulated drug delivery, photothermal cancer therapy, and imaging contrast agents. For example, in photothermal cancer therapy, nanoshells can be injected intravenously, accumulate at tumor sites due to the enhanced permeability and retention (EPR) effect and/or molecular targeting, then generate heat upon illumination with near infrared light, leading to destruction of the tumor. This has shown very promising results in several animal models. For example, in a mouse colon carcinoma model, we demonstrated 100% survival of nanoshell treated mice at 1 year. These materials are now in phase I human clinical trials. For use in diagnostics and imaging, nanoshells can be designed to strongly scatter near infrared light. Molecularly targeted nanoshells have been used as optical contrast agents for cancer imaging with sub-cellular resolution. For example, anti-HER2 conjugated nanoshells allow near infrared imaging of HER2+ breast carcinoma cells. Furthermore, integrated imaging and therapy applications have been accomplished with nanoshells designed to provide both absorption and scattering, potentially enabling “see-and-treat” approaches to cancer therapy.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr MS1-1.
International Breast Cancer Research: Launching an Expedition to the Moon.
Authors: Piccart M. 
Published: December 2010

Abstract
In his State of the Union address in 1971, President Nixon launched a "war on cancer" by calling for the "same kind of concentrated effort that split the atom and took man to the moon" to be turned towards conquering cancer. Since this landmark address, great strides have been made in the war on breast cancer. Lumpectomy with adjuvant radiotherapy, sentinel lymph node dissection, and adjuvant systemic therapy in the form of chemotherapy, hormonal therapy and trastuzumab have improved the quality of life and long-term survival of women diagnosed with early breast cancer. International collaboration involving research groups and initiatives such as the Early Breast Cancer Trialists' Collaborative Group quinquennial overviews has provided the clinical trials infrastructure and framework necessary to synthesize the evidence-based data upon which these gains have been achieved. Despite these successes, the pathway to new drug development and improved medical effectiveness today is costly, labor-intensive, and far too slow for our patients. Over the last decade, the advent of molecular technologies has dramatically improved our understanding of the biology of breast cancer. We now have targeted therapies available to inhibit specific signaling pathways that are aberrant in subpopulations of breast cancer. To further improve breast cancer care, we must fundamentally rethink how translational research is performed in clinical trials. The challenge of making personalized medicine a reality demands the launch of an expedition taking us to and beyond the moon: it will involve clinicians, basic scientists, bioinformaticians, statisticians, industry sponsors, regulators, and patients in new partnership that is committed to changing the vision, culture and methodology of breast cancer research. The Breast International Group's efforts in this direction will be presented.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr W1-1.
Assessment of the performance of the Stanford online calculator for the prediction of non-sentinel lymph node metastasis in sentinel node positive breast cancer patients.
Authors: Scow JS , Degnim AC , Hoskin TL , Reynolds C , Boughey JC 
Published: December 2010

Abstract
Abstract #1005
Background: Several models for the prediction of non-sentinel lymph node metastasis (+NSLN) in sentinel lymph node positive (+SLN) breast cancer patients have been published. Multiple variables have been shown to be important in prediction of +NSLN. To this date, models that utilize 7-8 variables have been significantly more discriminatory than models using only 2-3 variables. In this study, we evaluate the performance of the newly created Stanford online calculator (SOC) to predict the likelihood of +NSLN. The SOC uses 3 variables: primary tumor size, sentinel lymph node metastasis size, and presence/absence of lymphovascular invasion.&#x2028; Methods: From 1997-2004, 465 breast cancer patients with clinically negative axillae were found to have a +SLN and underwent completion axillary lymph node dissection (ALND) at the Mayo Clinic. Using the SOC the probability of having +NSLN was determined for each patient. Complete variable data was available for 464 patients which make up the cohort reported here. A receiver-operating characteristic (ROC) curve was created and the area-under-the-curve (AUC) was calculated. Mean probabilities of patients with and without +NSLN were compared. Additionally, patients with a low Stanford probability were examined to determine the model's accuracy in discriminating patients who could potentially be spared ALND. These results were compared to the results of the Mayo Clinic and Memorial Sloan Kettering Cancer Center (MSKCC) nomograms which have been previously applied to this same cohort of patients.&#x2028; Results: The AUC of the Stanford model was 0.72 (95% CI 0.67-0.77). The mean Stanford probabilities for patients with and without NSLN disease were 0.75 (range 0.06 to 1.0) and 0.50 (range 0.05 to 1.0), respectively (p &lt; 0.0001). Examining patients with a Stanford probability &lt;= 10%, we found that 47 patients met this criterion; 6 had +NSLN and 41 did not, for a false negative (FN) prediction rate of 13%. There was only 1 patient with Stanford probability &lt;= 5%, and this patient did not have +NSLN. The AUC of the MSKCC and Mayo nomograms in this same patient population was 0.74 and 0.77, respectively. The AUCs did not differ significantly (p = 0.13) among the 3 models.&#x2028; &#x2028; Conclusion: Despite using only three variables, the Stanford nomogram appears to perform as well as, but not better than the MSKCC and Mayo nomograms in our patient cohort. Further validation in other patient populations is needed prior to widespread utilization of this nomogram.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1005.
Technical aspects of the sentinel node biopsy in the EORTC AMAROS sentinel node trial.
Authors: Straver ME , Meijnen P , van Tienhoven G , van de Velde CJ , Mansel RE , Bogaerts J , Demonty G , Rutgers EJ 
Published: December 2010

Abstract
Abstract #1006
Background: The AMAROS trial is a phase III study comparing axillary lymph node dissection (ALND) with axillary radiation therapy (ART) in patients with proven axillary metastasis by sentinel node biopsy (SNB). The main objective of the trial is to prove equivalent locoregional control and reduced morbidity for ART. The aim of this interim analysis was to analyze the technical aspects of the SNB.&#x2028; Methods: The first 2000 patients with operable unifocal invasive breast cancer (5-30 mm) and clinically negative lymph nodes enrolled in the AMAROS trial between 2001 and 2005 were analyzed. The 26 participating institutions have been site visited as part of the surgical quality assurance. SNB is performed using preoperative lymphoscintigraphy, blue dye and a gamma-ray detection probe. Patients with a negative sentinel node were not subjected to ALND or ART.&#x2028; Results: The SN identification rate was 97% (range per institute 89%- 99%), 33% (n=658) of the patients were SNB positive, 62% (n=1245) were SNB negative and 2%(n=32) had other outcomes (non-axillary, missing data). Median two sentinel nodes were removed in the SNB positive as well as the SNB negative group. In 17% (344) of the patients, non-blue and non radio-active nodes were removed during the sentinel node procedure, median 1 node. In 11 patients, these nodes were the only tumor positive nodes found. In the SNB positive group the incidence of macro-, micrometastasis and isolated tumor cells was 61% (389), 26% (164) and 13% (80), respectively. In the ALND arm, further nodal involvement was seen 47,5% , 21,4 % and 16,7%, respectively. There was no correlation between the size of metastasis and the tumor size, grade or histological subtype. Of the sentinel nodes 59% (1907/3259) were radioactive and blue, 33% (1087/3259) were only radioactive, 8 %(265/3259) were only blue. Non-visualization on lymphoscintigraphy was seen in 7.6%(152), in 78%(118) of these cases a sentinel node was found during surgery. At least one sentinel node was located in the axilla in 89%(1777), in the internal mammary chain in 5% (104) and infra/supraclavicular in 1%(15). The injection site was intra/peritumoral in 53% subcutane/intradermal over the tumor in 9% periareolair in 16%, a combination in 4%, missing data 17%. Sentinel nodes in the internal mammary chain were significantly correlated with a intratumoral injection technique.&#x2028; Conclusions: These results indicate that with a 97% detection rate in this prospective international multicenter study using the combination of radioactive tracer and blue dye, the sentinel node procedure is highly effective. Differences in injection site affect the finding of non axillary sentinel nodes.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1006.
Intra-operative touch imprint cytology for assessing sentinel lymph nodes in patients with lobular breast cancer.
Authors: Fazel MZ , Gogalniceanu P , Patel A , Capitano A , Kocjan G , Falzon M , Douek M 
Published: December 2010

Abstract
Abstract #1008
Background: Touch imprint cytology (TIC) as a tool for intra-operative assessment of sentinel lymph nodes (SLN) in breast cancer has been shown to be rapid, reliable and cost-effective. Its use in lobular cancer is however more challenging due to the pattern of lymph node infiltration, smaller cells, similarity to lymphocytes and low grade cytomorphology. The aim of this study was to evaluate the sensitivity and specificity of intra-operative TIC in assessing SLN metastases in patients with lobular breast cancer.&#x2028; Material and Methods: All patients with lobular carcinoma who underwent intra-operative TIC assessment of the SLN were identified within our prospectively collected database. The SLN was bi-valved along its longitudinal axis and imprinted onto a slide at least six times before air-drying. The slide was treated with the rapid Giemsa stain before examination by one of three cytopathologists. Where TIC revealed SLN metastases, the patient underwent immediate axillary clearance. The SLN were then processed for histopathology by sectioning at three levels before haematoxylin and eosin staining. Those lymph nodes found to be negative then underwent immunocytohistochemistry staining before being declared truly negative. All patients with SLN metastases not identified during surgery received a delayed axillary clearance. The TIC results were compared to the final histopathology result of the SLN and the sensitivity and specificity calculated.&#x2028; Results: 51 patients with lobular cancer who underwent TIC were identified. The table below summarises the results:&#x2028; &#x2028; The sensitivity thus calculated was 76.0%; the specificity 100.0% and the negative predictive value 81.25%. Of the 6 false negative cases, 4 were grade 1 and 2 were grade 2. The mean primary tumour size in this group was 17mm (range 11 to 27mm). In all 6 cases, axillary metastases was found in 3 or fewer lymph nodes post axillary clearance.&#x2028; Discussion: This study demonstrates the reliability of using intra-operative TIC to evaluate SLN during surgery for lobular cancer. It compares very favourably to data published in the literature from other institutions that have examined the use of TIC in lobular carcinoma and may relate to the presence of experienced, highly motivated cytopathologists at our unit. In addition, it also compares well with other studies describing the use of TIC in ductal carcinoma, including our own unit's previously published data. Thus, in experienced hands, TIC is feasible with an acceptable accuracy allowing intra-operative SLN assessment in patients with lobular breast cancer.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1008.
The significance of intramammary lymph node metastases in breast cancer management.
Authors: Hogan BV , Peter MB , Shenoy HG , Horgan KM , Shaaban AM 
Published: December 2010

Abstract
Abstract #1009
Introduction &#x2028; Intramammary lymph nodes are defined as lymph nodes surrounded by breast tissue. They are a potential site of regional spread for breast cancer and metastases in this node is reported in up to 9.8% of operable breast cancers. Despite this, the existence of the intramammary node is not widely appreciated and the clinical significance of intramammary nodal metastases remains uncertain. The aim of this study is to determine the prognostic relevance of intramammary lymph node metastases and how it impacts on current breast cancer treatment modalities.&#x2028; Methods&#x2028; All patients with cytologically or histologically proven intramammary nodes were identified from the pathology database at the Leeds Teaching Hospitals. A total of 102 specimens were identified in 100 patients with a primary breast malignancy over a 13 year period (1994-2007). Clinical data including information on recurrences and death was obtained from patient records.&#x2028; Results&#x2028; One hundred patients were identified on our pathology database to have intramammary lymph nodes in association with a primary breast cancer. Ten were identified pre-operatively on breast imaging and 90 were first discovered on pathological assessment of excised breast tissue. Twenty one contained metastases. Factors that predicted for intramammary node metastases were lymphovascular invasion (p=0.002) and grade of tumour (p=0.012). The presence of metastases within the intramammary lymph node was associated with a poorer disease free survival (p=0.0072) and reduced overall survival (p=0.0128) at a mean follow up of 34.7 months. Sixty seven percent of patients with intramammary node metastases had further axillary metastases. In no case was the intramammary node identified as the sentinel node. One patient had an intramammary node metastases but benign axillary sentinel node. An axillary node clearance was not performed and she presented 19 months later with an axillary nodal recurrence.&#x2028; Conclusion&#x2028; The presence of intramammary lymph node metastases is associated with poorer outcome in breast cancer patients. Pre-operative detection of intramammary lymph node metastases is helpful to guide breast and axillary surgery. With the use of lymphoscintigraphy intramammary nodes will be increasingly identified as the sentinel node. Intramammary lymph node metastases predicts strongly for axillary metastatic disease and axillary node clearance should be recommended even when it is associated with a benign axillary sentinel node biopsy.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1009.
Predicting the burden of axillary disease in breast cancer patients with a positive sentinel node.
Authors: Unal B , Gur SA , Beriwal S , Johnson R , Ahrendt G , Bonaventura M , Soran A 
Published: December 2010

Abstract
Abstract #1010
Background: Current practice is to perform a completion axillary lymph node dissection (ALND) for breast cancer (BC) patients with tumor-positive sentinel lymph nodes (SLNs). However, not all patients with positive SLNs have further ALND. Katz et al suggested a nomogram for predicting having four or more positive nodes for SLN-positive BC which could change the adjuvant radiation treatment fields. Our goal is to validate the accuracy in predicting &gt; 4 positive axillary lymph nodes in BC patients with a positive SLN in our institution. Methods: Katz nomogram was developed from the multivariate logistic regression model using tumor histology, primary tumor size, lymphovascular space invasion, extranodal extension, the number of involved SLNs, the number of uninvolved SLNs, and the size of the largest SLN metastasis. Area Under (AUC) Receiver Operating Characteristics Curve (ROC) was calculated for the nomogram and a value more than 0.70 was accepted as providing considerable discrimination. Results: We reviewed the records of 319 patients with invasive BC and positive SLNs who underwent completion ALND at MWH of UPMC. None of these patients received neoadjuvant chemotherapy The mean age was 54.2 (30-84) years. Eighty-nine patients (27.8%) had four or more positive nodes. Histology was invasive ductal carcinoma for 86.2 % of patients. The median tumor size was 2.22 (0.5-8.0) cm. Seventy percent of patients had only one involved SLN. The median size of the largest SLN metastasis on H&E staining was 9.7 mm (range, &lt; 0.2 to 35 mm), and 24.4% of the patients had micrometastases (2 mm). Ninety nine patients (31%) had extranodal extension. The mean predicted probability of having ≥ 4 involved axillary LNs was 31.9 % (range, 1 to 99) in patients with ≥ 4 involved axillary LNs while it was it is 9.1% (range, 0.5 to 80) in patients having &lt; 4 axillary LN metastases (P&lt;0.001). The AUC value was 0.809. Conclusions: The Katz nomogram developed to predict having ≥ 4 involved axillary lymph nodes in BC patients with a positive SLNs is validated in our patients. Nomograms developed at other institutions should be used with caution when counseling patients regarding the risk of additional nodal disease. This nomogram will be helpful to clinicians making adjuvant treatment recommendations in practice.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1010.
Cost utility analysis on one-step nucleic acid amplification method for the detection of axillary metastasis in breast cancer.
Authors: Nishimura K , Sugiyama D , Moronobu A , Kawano S , Kumagai S 
Published: December 2010

Abstract
Abstract #1014
Back ground :OSNA method, One-step Nucleic Acid Amplification(OSNA) method is a new method for rapid detection of axillary lymph node metastases of breast cancer using PCR to detect cytokeratin 19's mRNA and different from conventional hsitopathological examination. It can be automated and can detect the axillary lymph node metastases quickly and precisely during operation. No cost effectiveness studies are conducted for this method.&#x2028; Materials and Method: We conducted the cost effectiveness analysis for this method comparing with conventional hsitopathological method using Markov models. We adopted the societal perspectives and the time horizon for fives years. We used TreeAge Pro 2005 (TreeAge Software Inc, Williamsontown, MA) to conduct Markov simulations. One way sensitivities analysis were conducted for all parameters. Cost and utilities data were collected from the studies and clinical trials for OSNA and conventional methods.&#x2028; Results: When the cost of OSNA is assumed as the same as intra-operative lymph node diagnosis by histopathology, the Markov model has shown the cost saving of $11,527/QALY by OSNA method. When the sensitivity analysis was performed by changing the cost of OSNA, the result has shown that OSNA can still show cost saving until the cost of OSNA method is $1,094 higher than the hsitopathological examination. Discussion: Our results clearly revealed OSNA methods is cost saving compared with convention intraoperative hsitopathological examinations. Result is robust for all parameters included in the model. Since OSNA method can avoid unnecessary re operations for axillary lymphadenectomy, this method can improve the quality of life for breast cancer patients.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1014.