bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract ES6-1: Quantitative Methods To Assess Eligibility for Breast Cancer Therapy
Authors: DL Rimm 
Published: April 2011

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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 &gt; 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 (&lt;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

Abstract
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

Abstract
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

Abstract
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

Abstract
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&lt;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.