bluuebunny/crossref_metadata_2025 huggingface dataset:
Bandgap Engineering in ZnO By Doping with 3d Transition Metal Ions
Authors: Joseph D. Paul , Venkateswaran C.
Published: April 2011

Bulk Zn0.95TM0.05O (TM=Cr, Mn, Fe, Co, and Ni) were synthesized by the standard ceramic method and explored for variation in their band gap energies using Diffuse Reflectance Spectroscopy in the ultraviolet-visible region. Phase quantification and compositional studies were performed using Rietveld analysis of the X-Ray Diffraction patterns, Scanning Electron microscopy, and Energy Dispersive X-Ray Analysis. Due to 3d transition ion doping, the samples have brilliant colors, and the absorption edge of Zn0.95TM0.05O was found to shift towards the visible and ultraviolet-visible region. The blue and red shifts in band gaps observed for various transition metal ion-doped ZnO are discussed.
Treatment of Facial Basal Cell Carcinoma: A Review
Authors: Smith Vanessa , Walton Shernaz
Published: April 2011

Basal cell carcinomas (BCCs) are locally destructive malignancies of the skin. They are the most common type of cancer in the western world. The lifetime incidence may be up to 39%. UV exposure is the most common risk factor. The majority of these tumours occur on the head and neck. Despite BCCs being relatively indolent the high incidence means that their treatment now contributes a significant and increasing workload for the health service. A good understanding of the options available is important. Management decisions may be influenced by various factors including the patient's age and comorbidities and the lesion subtype and location. Due to the importance of a good cosmetic and curative outcome for facial BCCs treatment decisions may differ significantly to those that would be made for BCCs arising elsewhere. There is little good randomized controlled data available comparing treatment modalities. Although traditionally standard excision has been the treatment of choice various other options are available including: Mohs micrographic surgery, curettage and cautery, cryosurgery, radiotherapy, topical imiquimod, photodynamic therapy and topical 5-fluorouracil. We discuss and review the literature and evidence base for the treatment options that are currently available for facial BCCs.
Encapsulation of Protein-Polysaccharide HIP Complex in Polymeric Nanoparticles
Authors: Gaudana Ripal , Khurana Varun , Parenky Ashwin , Mitra Ashim K.
Published: April 2011

The objective of the present study is to formulate and characterize a nanoparticulate-based formulation of a macromolecule in a hydrophobic ion pairing (HIP) complex form. So far, HIP complexation approach has been studied only for proteins with molecular weight of 10–20 kDa. Hence, we have selected bovine serum albumin (BSA) having higher molecular weight (66.3 kDa) as a model protein and dextran sulphate (DS) as a complexing polymer to generate HIP complex. We have prepared and optimized the HIP complex formation process of BSA with DS. Ionic interactions between basic amino acids of BSA with sulphate groups of DS were confirmed by FTIR analysis. Further, nanoparticles were prepared and characterized with respect to size and surface morphology. We observed significant entrapment of BSA in nanoparticles prepared with minimal amounts of PLGA polymer. Finally, results of circular dichroism and intrinsic fluorescence assay have clearly indicated that HIP complexation and method of nanoparticle preparation did not alter the secondary and tertiary structures of BSA.
Iterative Approximation of Common Fixed Points of Two Nonself Asymptotically Nonexpansive Mappings
Authors: Turkmen Esref , Khan Safeer Hussain , Ozdemir Murat
Published: April 2011

Suppose that K is nonempty closed convex subset of a uniformly convex and smooth Banach space E with P as a sunny nonexpansive retraction and F : = F(T1)∩F(T2) = {x ∈ K : T1x = T2x = x} ≠ ∅. Let T1, T2 : K → E be two weakly inward nonself asymptotically nonexpansive mappings with respect to P with two sequences satisfying (i = 1,2), respectively. For any given x1 ∈ K, suppose that {xn} is a sequence generated iteratively by , , n ∈ ℕ, where {αn} and {βn} are sequences in [a, 1 − a] for some a ∈ (0,1). Under some suitable conditions, the strong and weak convergence theorems of {xn} to a common fixed point of T1 and T2 are obtained.
Patients' Perceptions of Nurses' Behaviour That Influence Patient Participation in Nursing Care: A Critical Incident Study
Authors: Larsson Inga E. , Sahlsten Monika J. M. , Segesten Kerstin , Plos Kaety A. E.
Published: April 2011

Patient participation is an important basis for nursing care and medical treatment and is a legal right in many Western countries. Studies have established that patients consider participation to be both obvious and important, but there are also findings showing the opposite and patients often prefer a passive recipient role. Knowledge of what may influence patients' participation is thus of great importance. The aim was to identify incidents and nurses' behaviours that influence patients' participation in nursing care based on patients' experiences from inpatient somatic care. The Critical Incident Technique (CIT) was employed. Interviews were performed with patients (), recruited from somatic inpatient care at an internal medical clinic in West Sweden. This study provided a picture of incidents, nurses' behaviours that stimulate or inhibit patients' participation, and patient reactions on nurses' behaviours. Incidents took place during medical ward round, nursing ward round, information session, nursing documentation, drug administration, and meal.
Emerging Longitudinal Trends in Health Indicators for Rural
Residents Participating in a Diabetes and Cardiovascular Screening
Program in Northern Alberta, Canada
Authors: Ralph-Campbell Kelli , Oster Richard T. , Connor Tracy , Toth Ellen L.
Published: April 2011

Background. Geographic isolation, poverty, and loss of culture/tradition contribute to “epidemic” rates of diabetes amongst indigenous Canadians. The Mobile Diabetes Screening Initiative travels to rural indigenous and other remote communities in Alberta to screen for diabetes and cardiovascular risk. We sought to examine risk factors longitudinally. Methods. Clinical and anthropometric measurements were undertaken for 809 adults (aged 20–91) between November 2003 and December 2009. For those who had more than one MDSi visit, trend estimates (actual changes) were calculated for body mass index (BMI), weight, waist circumference, hemoglobin A1c (A1c), total cholesterol, and blood pressure. Results. Among those without diabetes (N=629), BMI and weight increased (P<.01) and blood pressure decreased (P<.05). For those with diabetes (N=180), significant improvements (P<.05) were observed for all indicators except waist circumference. Conclusion. Improvements observed suggest that MDSi's model may effectively mediate some barriers and support subjects in managing their health.
Nanospider Technology for the Production of Nylon-6 Nanofibers for Biomedical Applications
Authors: El-Newehy Mohamed H. , Al-Deyab Salem S. , Kenawy El-Refaie , Abdel-Megeed Ahmed
Published: April 2011

Nylon-6 nanofiber mat incorporated with 5,5-dimethyl hydantoin (DMH) as an antimicrobial drug was electrospun from formic acid. The morphology of the nanofiber mat using scanning electron microscope (SEM) showed that the obtained fiber had an average diameter of around 15–328 nm. The nanofiber was characterized by FTIR spectra, TGA, and DSC. The nanofiber containing drug showed initial fast release. It released about 55% of its drug content within the first two hours. Moreover, the antimicrobial activity of the electrospun nylon-6 nanofiber containing drug was examined againstEscherichia coli,Pseudomonas aeruginosa,Aspergillus niger, andAspergillus flavus. The nylon-6 nanofiber exhibited high inhibitory effects against the microbes. The results clearly indicate that the antimicrobial activity of the electrospun nylon-6 nanofiber containing drug varies with the species of the organisms used. Thus, the study ascertains the value of the use of electrospun nanofiber, which could be of considerable interest to the development of new antimicrobial materials. The microbes, examined by SEM, were totally deformed and exhibited severe destruction. Abnormal cell division was observed at high frequencies among cells that tried to divide in the presence of the nanofiber. Many cells were enlarged, elongated, empty ghosts, or fragmented, consistent with the extremely low viability.
NNK-Induced Lung Tumors: A Review of Animal Model
Authors: Zheng Hua-Chuan , Takano Yasuo
Published: April 2011

The incidence of lung adenocarcinoma has been remarkably increasing in recent years due to the introduction of filter cigarettes and secondary-hand smoking because the people are more exposed to higher amounts of nitrogen oxides, especially 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone(NNK), which is widely applied in animal model of lung tumors. In NNK-induced lung tumors, genetic mutation, chromosome instability, gene methylation, and activation of oncogenes have been found so as to disrupt the expression profiles of some proteins or enzymes in various cellular signal pathways. Transgenic animal with specific alteration of lung cancer-related molecules have also been introduced to clarify the molecular mechanisms of NNK in the pathogenesis and development of lung tumors. Based on these animal models, many antioxidant ingredients and antitumor chemotherapeutic agents have been proved to suppress the NNK-induced lung carcinogenesis. In the future, it is necessary to delineate the most potent biomarkers of NNK-induced lung tumorigenesis, and to develop efficient methods to fight against NNK-associated lung cancer using animal models.
Hypothesis: The Role of Sterols in Autism Spectrum Disorder
Authors: Lee Ryan W. Y. , Tierney Elaine
Published: April 2011

A possible role for sterols in the development of autism spectrum disorder (ASD) has not been proven, but studies in disorders of sterol biosynthesis, chiefly Smith-Lemli-Opitz syndrome (SLOS), enable hypotheses on a causal relationship to be discussed. Advances in genetic technology coupled with discoveries in membrane physiology have led to renewed interest for lipids in the nervous system. This paper hypothesizes on the role of sterol dysfunction in ASD through the framework of SLOS. Impaired sonic hedgehog patterning, alterations in membrane lipid rafts leading to abnormal synaptic plasticity, and impaired neurosteroid synthesis are discussed. Potential therapeutic agents include the development of neuroactive steroid-based agents and enzyme-specific drugs. Future investigations should reveal the specific mechanisms underlying sterol dysfunction in neurodevelopmental disorders by utilizing advanced imaging and molecular techniques.
Psychosocial Development and First Substance Use in Third and Fourth Grade Students: A Short-Term Longitudinal Study
Authors: Jones Randall M.
Published: April 2011

Third and fourth grade students () completed measures of psychosocial development, substance use, and intentions to use in January, and again in May, 1998. A revised Erikson Psychosocial Inventory Scale (EPSI) was employed to assess psychosocial development while estimates of substance use and intentions were obtained from anonymous self-reports. The sample was split on the basis of change in substance use and intentions from January to May. Using this grouping scheme as an independent variable, scores on the EPSI subscales (trust, autonomy, initiative, industry, and identity) were compared over time. Interestingly, no differences in psychosocial development were evident for the initial substance use comparisons, but differences were evident five months later. Respondents who initiated substance use and/or increased intentions during the five-month interval exhibited small gains (averaging less than 2.0%) on measures of trust, autonomy, and initiative and modest declines in industry and identity (−1.2%). Respondents who neither initiated substance use nor increased intentions during the five-month interval experienced significant gains (averaging 6.0%) on all five of the EPSI subscales. These findings suggest that early substance use may impede psychosocial development, thus justifying prevention efforts in the earlier grades as well as efforts to delay onset.
The Cretaceous Alkaline Dyke Swarm in the Central Segment of the Asunción Rift, Eastern Paraguay: Its Regional Distribution, Mechanism of Emplacement, and Tectonic Significance
Authors: Velázquez Victor F. , Riccomini Claudio , Gomes Celso de Barros , Kirk Jason
Published: April 2011

A structural analysis of Cretaceous alkaline dykes swarm associated with the central segment of the Asunción Rift is reported here. Dykes are generally single near-vertical tabular bodies, less than 5 m wide, although multiple and composite intrusions also occur. Many of these small bodies have been emplaced into Paleozoic sedimentary rocks and exhibit a regional NW-SE orientation pattern. Petrographical and geochemical data allow recognition of two different lineages of potassic dykes: a silica-undersaturated suite ranging from basanite to phonolite (B-P) and a silica-saturated suite ranging from alkali basalt to trachyte (AB-T). The morphological features, the regional en-échelon distribution, and the NW-SE orientation pattern suggest that the dykes were injected along fractures and faults, under a transtensional tectonic regime with σ1 NW/horizontal, σ2/vertical, and σ3 NE/horizontal. Detailed analysis, combining dyke petrography, orientation pattern, and relative chronology reveals a rotation from WNW toward NNW during dyke emplacement. In terms of the paleostress field orientation, the evidence indicates that the dykes were diachronically formed under a similar stress condition. Finally, the pattern of orientation documented for the Cretaceous alkaline dykes of the Asunción Rift is consistent, temporally and spatially, with the phases of regional deformation that occurred during the process of the Atlantic Ocean opening.
Abstract ES2-2: DNA Repair and Breast Cancer: Therapeutic Opportunities
Authors: Silver DP
Published: April 2011

The recognition that BRCA1 and BRCA2 have roles in DNA repair and that defects in either of these genes leads to specific therapeutic vulnerabilities has increased our understanding of why some tumors are susceptible to chemotherapy. Mutations in BRCA1 or BRCA2 cause defective homologous recombination, one of the fundamental systems for DNA repair. Preclinical modeling, clinical trials, and observations about acquired chemotherapy resistance all suggest strongly that mutations in BRCA1 or BRCA2 also sensitize tumors to the platinum agents, cisplatinum and carboplatinum, underscoring the important role of homologous recombination in response to these agents. Further, data concerning the increased dependence of cells with defects in another DNA repair system, base excision repair, on homologous recombination has led to the development of PARP inhibitors. These new therapeutic agents exploit this relationship between these DNA repair pathways and underscore the utility of synthetic lethality as a concept in drug development. These insights as they apply to breast cancer therapy will be discussed.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr ES2-2.
Abstract ES3-3: Management of Women with a High Predisposition to Breast Cancer: Standard of Care
Authors: Domchek SM
Published: April 2011

Women who have inherited germ line mutations in BRCA1 and BRCA2 are at significantly increased risk for breast and ovarian cancer. Fortunately, our understanding of the management of BRCA1 and BRCA2 mutation carriers has increased significantly in the 15 years since these genes were identified. There have been improvements in genetic testing techniques resulting in fewer “missed” BRCA1 and BRCA2 mutations, as well as a better understanding of the risks of these mutations. Incorporating breast MRI into screening results in earlier detection of breast cancer. Prophylactic mastectomy significantly reduces breast cancer risk, while improvements in reconstructive surgery allow women more options. Risk reducing salpingo-oophorectomy in BRCA1/2 mutation carriers decreases breast cancer risk, ovarian cancer risk and improves breast cancer specific-, ovarian cancer specific-and overall survival. Emerging data suggest that BRCA1/2 mutation testing can play a role in newly diagnosed breast cancer, particularly from the standpoint of surgical decision making. Finally, knowledge of BRCA1 and BRCA2 mutation status has the potential to impact decisions on systemic therapy as will be reviewed.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr ES3-3.
Abstract ES4-1: Statistical Challenges in Predictive and Prognostic Biomarker Studies: How To Avoid Wasting Your Time and Specimens
Authors: McShane LM
Published: April 2011

A better understanding of tumor biology through identification of specific biological characteristics of tumor and host that predict tumor behavior and responsiveness to therapy will be essential for the discovery of new therapies and for optimization of cancer care for individual patients. Progress in identifying promising biomarkers in correlative studies and moving them to the clinic has been slow. Many correlative studies are conducted without clearly specified hypotheses, have poor statistical designs, use assays that are not standardized or lack reproducibility, and often employ inappropriate or misleading statistical analysis approaches. Common statistical problems include underpowered studies or overly optimistic reporting of effect sizes and significance levels due to multiple testing, subset analyses, cutpoint optimization, and model overfitting. For studies aiming to a assess a biomarker's ability to guide treatment decisions, the importance of appropriate control groups and the potential for confounding of prognostic and predictive effects have been underappreciated. Compounding these problems, many correlative studies have not been reported in a rigorous fashion, and published articles often lack sufficient information to allow adequate assessment of the quality of the study or the generalizability of the results. Suggestions are provided for how to avoid some of the common statistical pitfalls, how to identify problematic studies, and how to report correlative studies to maximize the interpretability and usefulness of the results.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr ES4-1.
Abstract ES4-2: The importance of Technical Validation
Authors: Reis-Filho JS
Published: April 2011

The development of biomarkers for the diagnosis and classification of breast cancers and stratification of breast cancer patients into clinically meaningful groups is one of the lynchpins of individualised medicine. The correct and robust assignment of patients into subgroups of therapeutic relevance is of utmost importance. In breast cancer management, this is currently performed through the analyses of a few immunohistochemical markers (e.g. oestrogen receptor, progesterone receptor and HER2), fluorescence and/or chromogenic in situ hybridisation, protein analysis of lysates, and quantitative real-time PCR. It has become patently clear, however, that these markers are not sufficient for the potential of individualised therapy to be realised. With the advent of high throughput technologies, fundamental and translational research approaches have provided a wealth of data on diagnostic markers, potential prognostic and predictive markers, and therapeutic targets, which ultimately will need to be incorporated in clinical practice. Some of the major challenges in this process are to determine the accuracy of the research hypothesis, the exclusion of potential biases, and to define whether the reagents and methodologies are fit for purpose. This requires a thorough assessment of the accuracy, robustness and reproducibility of the markers and the methods for their analysis. For instance, immunohistochemistry has become one of the major tools for the identification of expression of potential markers in cancer tissues; albeit at first glance trivial to perform, immunohistochemical analysis can be affected by numerous parameters that can affect its accuracy. Likewise, several approaches for the identification of molecular subgroups by gene expression profiling have been shown not to assign the same patients into the same molecular subgroups consistently. Interpretation of in situ hybridisation is also fraught with difficulties and discrepancies have often been attributed to intra-tumour heterogeneity rather than technical variation. The challenges for the assessment and validation of biomarkers in human tissues and the approaches to overcome them will be discussed.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr ES4-2.
Abstract ES6-1: Quantitative Methods To Assess Eligibility for Breast Cancer Therapy
Authors: DL Rimm
Published: April 2011

Breast cancer is one of the few tumors where the judgment of level of protein expression by immunohistochemistry (IHC) directly results in therapy. Although the pathologist is not the prescribing physician, their “reading” of ER, PR, and Her2 can result in prescription of life-saving therapies. As a result of that, many studies have been done to attempt to be more quantitative in the assessment of exactly how much protein is on the slide. However, these efforts have largely failed to gain clinical acceptance, even up to April 2010, when the ASCO/CAP guidelines recommended, but did not require, a quantitative approach. Key reasons for the hesitation to require quantification included lack of standardization, lack of data on pre-analytic variables and lack of a universally accepted reproducible quantitative method. This presentation will examine the current methods for quantitative measurement of ER and Her2 in breast cancer tissue including review of the current technologies and devices for both IHC and quantitative immunofluorescence (QIF). Then issues and some new data related to standardization and pre-analytic variability will be presented.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr ES6-1.
Abstract ES7-1: Next Generation Sequencing for the Clinician: A Breast Cancer Study
Authors: Mardis ER , Ding L , Shen D , Wallis J , Chen K , Watson M , Hoog J , Ellis MJ , RK Wilson
Published: April 2011

The ability to study genome-wide sequence alterations in cancer genomes has transformed our understanding of the intricacies of this disease. We have applied whole genome sequencing and analysis to tease apart the genomic predictors of aromatase inhibitor (AI) response, by selecting luminal breast cancer cases obtained within a clinical trial of aromatase inhibitor treatment (ACOSOG Z1031). Our study compared the constitutional genome to the cancer genome for patients that exhibit either a response or a resistance phenotype, based on their Ki67 IHC score following 4 month AI treatment and resection. My talk will highlight the process by which these genomes are sequenced and analyzed, and will provide our most recent insights into how the combination of the constitutional and somatic genomes determine whether a patient will respond to AI treatment.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr ES7-1.
Abstract ES8-1: Systems Biology — Can It Explain Everything?
Authors: Faratian D
Published: April 2011

Systems biology has entered the biological lexicon but is only just gaining acceptance within the clinical community. Some reasons for slow uptake include a misunderstanding of the opportunities (and limitations) offered by systems approaches, an absence of real-life ‘success-stories’ of clinical application, and perhaps deficiencies in cross-disciplinary training and multidisciplinary teamwork. Nevertheless, breast cancer, and its management, is complex and multi-parametric and therefore ideally suited to the systems approach. There are a number of opportunities to apply systems biology to real clinical problems, such as drug and biomarker discovery, the integration of clinical and biological data for therapeutic decision-making, and refining pharmacogenetic and pharmacogenomic algorithms for prognosis and prediction in breast cancer patients. In some of these areas there has been success, in others a more complete understanding of systems biology is required in order to tailor new technologies, mathematics, and clinical trial design to successfully utilize systems approaches. In this talk I will discuss where and how systems biology may be useful to the clinician, both now and in the future.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr ES8-1.
Abstract ES8-2: Modeling Sensitivity to Therapeutic Agents
Authors: Spellman PT
Published: April 2011

Single agent targeted chemotherapeutics are now being deployed with the goal of revolutionizing clinical treatments. It is likely that many of these agents will be successfully used to improve outcomes for patients, and potentially in patients with localized disease there may even be cures as are seen with Trastuzumab. Unfortunately it is unlikely that single agent therapies, or targeted therapies in conjunction with standard chemotherapies will provide cure to the many patients who have metastatic disease. The true challenge then is the use of multiple targeted therapies to systematically disrupt and eliminate tumors based on the use of genomic and systems modeling. Modeling therapeutic responses of individual tumors will require not just knowledge of the pathways that tumors use (or misuse) but will also require knowledge of how these pathways interact. Equally important, to avoid side effects, it will be essential to understand these systems across the body. New initiatives are now underway to construct these models (both computational and biological) and test them in the laboratory. The challenge then is to move the models from models to patients by fostering collaborative interactions between pharmaceutical companies, systems biologists, and clinicians. I will illustrate these principles by showing how we attempt to address them in our own work.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr ES8-2.
Abstract MS1-2: Long Noncoding RNAs in Breast Cancer Progression
Authors: HY Chang
Published: April 2011

Long intergenic noncoding RNAs (lincRNAs) are pervasively transcribed in the genome, yet their potential involvement in human disease is not well understood. Recent studies of dosage compensation, imprinting, and homeotic gene expression suggest that individual lincRNAs can function as the interface between DNA and specific chromatin remodeling activities. We found that many lincRNAs become systematically dysregulated during breast cancer progression. A lincRNA termed HOTAIR is increased in expression in primary breast tumors and metastases, and HOTAIR expression level in primary tumors is a powerful predictor of eventual metastasis and death. Enforced expression of HOTAIR in epithelial cancer cells induced genome-wide re-targeting of Polycomb Repressive Complex 2 (PRC2) to an occupancy pattern more resembling embryonic fibroblasts, leading to altered histone H3 lysine 27 methylation, gene expression, and increased cancer invasiveness and metastasis in a manner dependent on PRC2. Conversely, loss of HOTAIR can inhibit cancer invasiveness, particularly in cells that possess excessive PRC2 activity. A second long noncoding RNA, named PANDA, is part of the DNA damage response mediated by p53 and controls the balance between cell death and cell cycle arrest. Collectively, these findings suggest that lincRNAs play active roles in modulating the cancer epigenome and may be important targets for cancer diagnosis and therapy.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr MS1-2.
Abstract P1-01-04: Axillary Intervention in Patients Undergoing Neoadjuvant Therapy (NST) — First Results from the SENTINA Study
Authors: Thorsten K , Bauerfeind I , Fehm T , Fleige B , Gisela H , Lebeau A , Liedtke C , Mai M , Von Minckwitz G , Schrenk P , Staebler A , Untch M.
Published: April 2011

Background: The optimal scheduling for sentinel lymph node biopsy (SLNB) among patients with breast cancer undergoing neoadjuvant systemic therapy (NST) is unclear. SENTINA-study is the first prospective multicenter trial that systematically examines the feasibilty and reliability of SLNB prior to and after (NST). Here we present results of a first exploratory analysis by examining distribution of N-stages in the different treatment arms and correlating the axillary status with the type of breast surgery (breast conserving therapy [BCT] vs mastectomy [ME]).

Methods: The SENTINA study is a four-arm multicenter (n= XXX) observation study. Patients will be stratified based on their clinical lymph node status prior to treatment. If the lymph node status is clinically negative SLNB is performed before NST. Patients with a negative SLN will undergo no further axillary surgery (Arm A), whereas patients with a positive SLN will be treated with sentinel-node-guided axillary dissection (SLNB-AD) after NST (Arm B). If the lymph node is clinically positive upon initial presentation, patients will undergo NST prior to any axillary intervention. If patients convert to a clinically negative lymph node status through NST they will undergo SLNB-AD (ARM C). Patients with persistent positive nodes or whose tumors progress under NST undergo primary axillary dissection (Arm D). Clinically node positive patients will be endcouraged to undergo FNA to confirm their lymph node status. A total of 1508 patients in the entire study will be needed to calculate the false-negative rate in this group with a one-sided 95% confidence interval not exceeding 10%.

Results: 873 patients have been accrued into SENTINA until may 31th 2010, 523 (59,9%) have completed their treatment. 180 (34,4%) women have been treated in Arm A and 117 (22,4%) in Arm B. In 170 (32,5%) patients the clinical axillary status converted from a clinical positive to a clinical negative status (Arm C). In 65 pts (12,4%) the axillary status remained positive or the tumor progressed under NCHT (Arm D). BCT rates in Arm A-D were 88.3%, 75.2%, 61.8% and 22.2% respectively.

Conclusion: First results of the SENTINA study show a strong correlation between the axillary status and the type of breast surgery in patients, who are treated with NST. Importantly, we demonstrate that the clinical assessment of the axillary status is unprecise. There is an urgent need to optimize the tailoring of axillary intervention in the setting of NST

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-01-04.
Abstract P1-01-13: Immediate Breast Reconstruction after Mastectomy in Invasive Breast Cancer: Identification of Patients Not Needing Postoperative Radiotherapy
Authors: Moorman AM , de Leeuw D , Bourez RLJH , Leeksma NG , Kouwenhoven EA.
Published: April 2011

Background: Immediate breast reconstruction after ablative breast surgery is psychologically and cosmetically preferable above second stage reconstruction. Since postoperative radiotherapy strongly increases risk of implant loss, it is a challenge to select preoperatively those patients who do not need postoperative locoregional radiotherapy after breast reconstruction. Besides radicality of tumour resection, it would be helpful to accurate identify N0-1 positive patients preoperatively. Aim: Risk assessment of postoperative locoregional radiotherapy in breast cancer patients with preoperative negative axillary lymphnodes. Patients and Methods: During period January 2007-2010 478 consecutive primary breast cancer patients were analysed. Each patient had regular X-mammography and breast ultrasonography. Ipsilateral axillary ultrasonography was routinely performed in case of BIRADS 4, 5 or 6 status of the breast tumour. Suspected lymphnodes (thickness of cortex > 2.3mm) were analysed by cytology or histology. Sentinel node biopsies (SNB) were harvested after Scintigraphy and Patent Blue Dye injection. Pathologic examination of SNB were classified as macrometastais (2mm), micrometasasis (0,2-2mm), isolated tumour cells (<0,2mm). Complete axillary lymphnode dissection (ALD) was routinely performed when one micro-or macrometastasis was present in the SNB, according to the Dutch Guidelines.

Results: Threehunderd fourty four patients had radiological unsuspected axillary lymphnodes (77.5%). Their tumour-status was cT1 (216), cT2 (68), cT3 (4).

In all these 344 patients 82 micro-and macrometastasis were found in the first SNB. Secondary ALD showed ≥4 metastasis in 5 patients: One of these 5 patients had a cT1c tumour, two a cT2, and two had a tumour larger than 5 cm. Overall risk for ≥4 positive lymphnode in patients with radiological unsuspected lymphnode is (5/344) 1.5%. Based on cT-status the risk for ≥4 positive lymphnodes with radiological unsuspected lymphnodes is 1/216 (0.46%) for cT1, 2/68 (3%) for cT2, 2/4 (50%) for cT3 tumours, respectively .

Conclusion: Risk for postoperative locoregional radiotherapy is minimal for cT1-2 breast cancer patients with preoperative radiological unsuspected axillary lymphnodes. Direct reconstruction after ablative therapy for these patients appears to be safe.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-01-13.
Abstract P1-01-23: Magnetic Sentinel Lymph Node Detection for Breast Cancer
Authors: Johnson L , Pankhurst QA , Purushotham A , Brazdeikis A , Douek M.
Published: April 2011

Background

The combined technique is the preferred technique for sentinel lymph node biopsy (SLNB) but blue dye and radioisotope both have significant drawbacks including poor pre-operative imaging, radiation exposure regulation, blue dye obscuring the surgical field and skin tattooing. We have developed a non-invasive non-radioactive method for SLNB using magnetic nanoparticles and a handheld magnetometer (SentiMag), and have previously demonstrated proof of principle in an ex-vivo pilot study. Materials and methods

Patients with newly diagnosed breast cancer underwent SLNB following injection of patent blue dye (Guerbet, Paris), radioisotope and 2ml of superparamagnetic iron oxide (Endorem, Guerbet, Paris). Endorem was injected subcutaneously at the circumareolar aspect of the upper outer quadrant in the affected breast. Intraoperatively, the SLN was identified using a combination of blue staining, black staining and gamma probe. Nodes were considered to be SLNs if their count exceeded 1/10th of the highest ex-vivo gamma count for any lymph node in that patient. Ex-vivo, gamma and SentiMag counts were compared. Receiver-operator curves were used to identify the optimal detection count for SentiMag. Results

Of 32 patients, 1 was excluded for technical failure of the device intra-operatively. In all patients 1 or more sentinel nodes were detected with the combined technique (31/31). In 26/31 (84%) patients the node was positive for superparamagnetic iron oxide. Receiver-operator curves demonstrated a SentiMag reading of 20 units or above which was the optimal cut-off for SLN detection (sensitivity 61.75% specificity 62.5%).

Success by node and by patient of the combined technique and the SentiMag technique

Discussion

Sentinel node biopsy using magnetic nanoparticles is feasible and the optimal cut-off point for sentinel node detection is 20 units. Further evaluation is needed to identify optimal injection dose and time delay between injection and nodal harvest in order to improve sensitivity and specificity.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-01-23.
Abstract P1-01-26: Clinical Implications of pN0 mol+ in Breast Cancer Patients
Authors: Falo C , Varela MAR , Moreno A , Villalba E , Serra JM , Benito E , Fernandez A , Morilla I , Guma A , Escobedo AP.
Published: April 2011

Introduction: Axillary lymph node involvement is the most significant prognostic factor in breast cancer patients. The real-time PCR (RT-PCR) appeared to be a sensitive method to diagnose the lymph node axillary stage, but the clinical relevance of pN0 (mol+) has not yet been established. We present the clinical characteristics of the subgroup of patients diagnosed as pN0 (mol+) and their clinical outcome after a mean follow-up of 72 months.

Material & Methods: Between June 2000 and November 2006, 674 patients with T1-T3 primary invasive breast cancer and low probability of axillary lymph node involvement, were included in a prospective study of the molecular analyses of the sentinel lymph node (SLN) biopsy. Each SLN was bi-dissected; one half was snap frozen for subsequent molecular analysis, on the other half, routine pathological analyses was performed, including immunoassaying for cam 5.2 antibody. The molecular analyses was performed by RT-PCR using the gene marker KRT 19. Adjuvant treatment and clinical outcome has been recorded after a mean follow-up of 72 months.

Results: 135 cases were staged as pN0 (mol+). Most of them corresponded to infiltrating ductal carcinoma (95%), 2.2% lobular, 1.5% colloid and 1.5% medullar. Nuclear grade: I in 5% of cases, II in 35% and III in 34% of them. By tumour stage, 1.5% were pT1a; 24% pT1b: 58% pT1c; 15% pT2 and 1.5% pT3. According to molecular subtypes, 73% of cases were luminal, 18.5% triple negative ones and 8.5% HER2 positive. All the patients except 5 ones received adjuvant systemic treatment: 41.5% hormonal therapy for at least 5 years; 32% chemotherapy followed by hormonotherapy and 18.5% chemotherapy, of those two patients received trastuzumab for 1 year. At the time of the analysis, there have been 4 local recurrences, 3 metastasic recurrences and 2 contra lateral ones. For survival analyses, 2 cases were excluded for presenting a previous breast cancer history, and one patient died after the last CMF from a septic shock. Of the 132 resting patients, 122 are free of relapse at the time of this analysis, the 3 patients with distant metastasis are on treatment for metastatic disease, 2 patients were death by other neoplastic diseases and 5 cases were death by other medical causes (4 cardiac and 1 respiratory failure). Survival rate for N0 mol+ was 94%, no specific breast cancer death have occurred at the present survival analyses.

Conclusions: Tumours diagnosed as pN0 (mol+) presented clinical and molecular characteristics of worse prognosis than pN0 (mol-) and this is translated in a higher proportion of patients staged N0 (mol+) treated with chemotherapy than pN0 (mol-). Survival in this subgroup of patients is high in relation to the adjuvant treatment delivered.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-01-26.
Abstract P1-01-27: Level III and Interpectoral Lymph Nodes Involvement in Breast Cancer with Positive Axillary Lymph Nodes after Neoadjuvant Chemotherapy
Authors: Fan Z , Li J , Wang T , Xie Y , Fan T , Lin B , Ouyang T.
Published: April 2011

Background: In the era of sentinel node biopsy (SNB), mainly aimed at local control, the axillary dissection (AD) was performed for breast cancer with positive node. It was argued that only level I/II lymph nodes dissection might be inadequate because nodes involvement was found in level III and interpectoral region when axillary node was positive. It is necessary to assess the extent of AD after modern preoperative axillary staging. The aim of this study was to investigate the incidence and associated factors of node involvement in level III/interpectoral region. Methods: A consecutive series of 338 core needle biopsy confirmed T0-2 invasive breast cancer cases were included in this study. Axillary node metastases were proved by ultrasound guided needle biopsy (NB) if ultrasonographic abnormal node was detected prior to SNB or by SNB if no abnormal node was detected. Cases of negative NB but positive SNB with image abnormal node were excluded. Prior to AD included level III and interpectoral lymph nodes, 4 to 8 cycles of neoadjuvant chemotherapy with anthrocyclin and/or taxane regimen were completed for each case. The chi-square test was used to determine the relation between level III/interpectoral lymph nodes metastases and clinicopathological factors. Multivariate logistic regression was analyzed for covariate selection. Results: A median of 19 axillary nodes was harvested per case (range: 5-46, average: 19.2). The pathologic complete response rate of axillary nodes was 35.3% (70/198) in NB positive subgroup. Level III and interpectoral lymph nodes were harvested in 76.9% (260/338) of cases (range: 1-8, average: 1.9, median: 1) and 49.7% (168/338) of cases (range: 1-10, average: 1.6, median: 1), respectively. The incidence of positive level III and interpectoral lymph nodes were 8.9% (30/338) and 8.9% (30/338), respectively. Node involvement of level III/interpectoral region was found in 13.3% (45/338) of these cases. The incidence of node involvement in level III/interpectoral region of NB positive subgroup (14.6%, 29/198) was not significantly higher compared with SNB positive subgroup (11.4%, 16/140, P=0.391). Increasing tumor size was significantly correlated with increasing likelihood of node involvement in level III/interpectoral region (T0-1: 6.3% vs T2: 16.7%, P=0.008). In SNB positive T0-1 subgroup, there was no positive node found in level III/interpectoral region. Multivariate analysis showed that tumor size was the only independent factors predicting node involvement in level III/interpectoral region (OR=3.488, 95%CI:1.427-8.528, P=0.006).

Conclusions: The incidence of node involvement in level III/interpectoral region was 13.3% of nodes positive T0-2 breast cancer treated with neoadjuvant chemotherapy. Tumor size may be the predictor of node involvement in this region.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-01-27.
Abstract P1-01-29: Clinical and Histopathological Factors Affecting Failed Sentinel Node Localization in Axillary Staging for Breast Cancer
Authors: Dordea M , Colvin H , Pujol Nicolas A , Oshodi T , Iwuchukwu O.
Published: April 2011

Background: Sentinel lymph node biopsy (SLNB) has become the standard of care in axillary staging of clinically node-negative breast cancer patients. We hypothesize that clinical parameters are associated with failure to identify an axillary sentinel lymph node.

Methods: We performed a retrospective review of 164 consecutive breast cancer patients who underwent SLNB from March 2008 to January 2010. A superficial injection technique was used as advocated by the UK National Training Programme (NEW START). All patients had lymphoscintigrams. Delayed imaging was performed if initial lymphoscintigram was negative up to 22 hours post-injection. Patient/surgical data, histopathological data and tumour location data were recorded. A univariate and multivariate analysis was performed.

Results: Mean time from radiocolloid injection to surgery was 785.10 minutes (SD 435.97). 9/164 patients failed to show nodes on delayed imaging. In 2/9 patients successful SLNB was carried out following subareolar blue dye injection and 5 minute massage. 6/9 patients showed no evidence of radioactivity or blue dye. These patients underwent a stage 2 axillary clearance. 5/6 had multiple node involvement. Age and nodal status were significant factors (P<0.05). For every unit increase in age there was a 9% (CI, 0.84 - 0.99) reduced chance of failed sentinel node localization. Patients with negative nodal status had a 90% (CI, 0.02 - 0.99) reduced risk of failed sentinel node localization than patients with nodal macrometastasis and extracapsular nodal invasion. Weight (p=0.063, CI 0.91 - 1.03), previous breast surgery (p=0.062, CI 0.006 - 1.136) and tumour location (p=0.402, CI 0.03 - 4.17) showed weak association but failed to reach statistical significance.

Discussion: Our results suggest that aberrant lymphatic flow secondary to tumour burden increase the chance of failed axillary sentinel node localization. Review of lymphoscintigrams showed that in all failed localizations the radiocolloid persisted around the injection site, showing limited local diffusion only. Similar findings were observed for blue dye injection. We further hypothesize that technical factors at the time of the injection may also play a role.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-01-29.
Abstract P1-01-32: Usefulness of Clinical Exploration, Ultrasound and MRI for the Assessment of Axillary Lymph Nodes Status Previous to the Performance of Sentinel Node Depends on Tumor Molecular Subtype
Authors: Sabadell D , Vernet-Tomas MDM , Colome C , Rodriguez-Arana A , Plancarte F , Carreras R.
Published: April 2011

Introduction: A high detection of positive lymph nodes previous to the surgical procedure lowers the probability of a false negative sentinel node. The sensibility and specificity of different imaging methods could depend on the molecular features of each tumor

Objective: The aim of this study was to study sensibility and specificity of clinical exploration, ultrasound and MRI to assess the status of axilar lymph nodes in different molecular subtypes.

Material and Methods: we retrospectively reviewed T1 and T2 breast cancers not candidate for neoadjuvant chemotherapy, treated in our breast cancer unit from September 2008 to May 2010. Data on clinical exploration (CE), axillary ultrasound (AU) and MRI were reviewed for each patient. The pathology exam of the surgical specimen (sentinel node or lymph node dissection) was reviewed for each patient and sensibility and specificity were calculated for each exploration method. Sensibility and specificity were also calculated separately considering five different molecular subtypes: Tubular A, Tubular B, Triple negative tumors, cerbB2 positive tumors and lobular tumors.

Results: 290 patients with T1 and T2 breast cancer were included in the study. Sensibility for CE was 26.76% and specificity 91%. Sensibility for AU was 38.46% and specificity 86.81%. Sensibility for MRI was 44.06% and specificity 86.02%. For Tubular A tumors, the highest sensibility was for MRI (40%) and the best specificity for CE (91.35%). For Tubular B tumors, the highest sensibility was for CE (33.33%) and the highest specificity for AU (100%). For Triple negative tumors, the highest sensibility was for MRI (100%) and the highest specificity for CE (89.47%). For cerbB2 tumors, the highest sensibility was for MRI (75%) and the highest specificity was for CE (100%). For Lobular tumors, the highest sensibility and specificity were for AU (50% and 93.33%, respectively).

Conclusion: MRI is the exploration with a higher sensibility to assess the preoperative status of axillary lymph nodes considering all the tumors together and in Tubular A, Triple negative and cerbB2 positive tumors. MRI sensibility is specially high in Triple negative and cerbB2 positive tumors. When choosing different imaging methods to assess axilar status, molecular subtype should be considered.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-01-32.