bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract CS01-2: The role of radiation in the treatment of the axilla in the setting of neoadjuvant chemotherapy
Authors: Fowble B 
Published: August 2014

Abstract
There is considerable controversy regarding the appropriate surgical procedure and its timing for evaluating the status of the axillary nodes in the neoadjuvant setting. Sentinel lymph node (SLN) surgery following initial chemotherapy avoids an axillary dissection and its associated morbidity in clinical N0 patients who have pathologic negative SLN. SLN identification and false negative rates (FNR) have been acceptable in these women and axillary recurrence rates without radiation directed to the axilla are £1%. For clinical N1 disease, 2 recent studies (SENTINA, ACOSOG 1071) reported SLN identification rates of 80% and 91%, FNR of 12.8 and 14% and ypN0 rates of 52% and 40% respectively. The SLN was the only positive node(s) in 58% and 40% of the ypN1 patients. Several studies have evaluated the role of regional node (RN) irradiation in clinical N1 patients who are ypN0 following neoadjuvant chemotherapy and have found no improvement in local-regional disease free survival. RN failure rates are low as reported by the NSABP B18 and 27 trials in the absence of post mastectomy radiation or with breast only radiation. The question of RN radiation is being addressed by an NRG (NSABP-RTOG) randomized trial. For women with clinical N1 disease who remain ypN1, axillary radiation may substitute for axillary dissection. Axillary radiation has been shown in randomized trials to be equivalent to axillary dissection in the adjuvant setting for clinical N0 women (NSABP B04) including those with positive SLN (Dutch Mirror, IBCSG 23-01, AMAROS). The Alliance trial will address this question. The potential advantage of neoadjuvant chemotherapy is the ability to adjust surgical and radiation treatment based on pathologic response and thereby minimize the morbidity of combined therapy. Various clinical scenarios will be presented with treatment options.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr CS01-2.
Abstract ES04-1: Basic science 101 – Targeting cell signaling in breast cancer
Authors: Yee D 
Published: August 2014

Abstract
Since normal cells require extracellular signals to proliferate, it seems likely that some transformed breast cancer cells can still respond to these signals. This premise is now well established; disruption of estrogen receptor function, important in normal mammary gland biology, by estrogen deprivation (ovarian suppression or aromatase inhibition) or selective estrogen receptor modulators demonstrated the clinical value of interrupting these key signaling pathways. Further advances have included the disruption of the human epidermal growth factor 2 (HER2) by monoclonal antibodies and tyrosine kinases. These successes have generated greater enthusiasm for identifying mechanism of action of cell signaling with the hope of identifying new therapeutic targets. The intracellular signaling pathways that transduce proliferative signals is becoming better understood. Activation of the phosphatidyl 3-kinase (PI3K) and the mitogen activated protein kinase (MAPK) pathways are required for normal and malignant cell growth. Multiple strategies and drugs have been developed to target these pathways and are in clinical trial. It is also evident that co-targeting of new or established pathways also have utility over targeting only one molecule. For example, the demonstration that estrogen receptor targeting and mTOR inhibition has clinical value has revealed the potential for the inhibition of multiple pathways. Similar advances have been made in targeting HER2 by both trastuzumab and pertuzumab. These clinical strategies have value as combination therapy may more fully suppress cell signaling than single agent therapy. Additional concepts and strategies will be discussed based on the established targets of estrogen receptor and HER2.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr ES04-1.
Abstract ES08-2: Predicting tumor response by functional imaging, PET imaging as a functional predictive biomarker
Authors: Mankoff D 
Published: August 2014

Abstract
The ability to measure biochemical and molecular processes to guide breast cancer treatment represents a significant advance in individualized breast cancer treatment. These assays have traditionally been performed by analysis of cell culture or tissue samples. More recently, functional and molecular imaging allows in vivo assay of biochemistry and molecular biology that is highly complementary to tissue-based assay. Molecular imaging can help inform drug trial of targeted breast cancer treatment and clinical decision making by (1) measuring regional expression of the therapeutic target, (2) testing the ability of drugs to interact with their intended targets, and (3) by measuring cancer response early in the course of treatment.
This talk will review basic principals of molecular imaging in breast cancer, with an emphasis on those methods that have been tested in patients. The talk will review the current state of molecular imaging in breast cancer patients, including methods in routine clinical use, those undergoing advanced clinical trials, and those in early-phase testing. Current trials and future directions will be highlighted.
The session is designed for a broad audience, ranging from breast cancer translational scientists to practicing physicians caring for breast cancer patients.
References
1. Mankoff DA. Molecular imaging as a tool for translating breast cancer science. Breast Cancer Res. 2008;10 Suppl 1:S3.
2. Specht JM, Mankoff DA. Advances in molecular imaging for breast cancer detection and characterization. Breast Cancer Res. 2012 Mar 16;14(2):206.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr ES08-2.
Abstract ES09-3: Symptom management and quality of life in metastatic breast cancer
Authors: Niravath P 
Published: August 2014

Abstract
Approximately 40,000 women in the US die each year of metastatic breast cancer. Because the disease is incurable at this stage, effective symptom management and preservation of quality of life are paramount for these patients. For those with brain metastases, consideration of cognition, quality of life, and overall survival are extremely important because some subsets of patients with breast cancer metastases to the brain may now enjoy prolonged survival of almost 2 years. For solitary brain metastasis, surgical resection followed by whole brain radiotherapy is known to prolong survival, though the addition of whole brain radiotherapy is associated with significant cognitive impairment and decreased quality of life without clear improvement in overall survival. Stereotactic radiosurgery (SRS) shows promise as a therapeutic option for patients with asymptomatic, smaller brain lesions. SRS, as compared to open surgery, results in improved quality of life. Bone metastasis is another common management dilemma for breast cancer patients. Commonly used bone agents, such as bisphosphonates and RANK ligand inhibitors, are known to decrease bone pain and increase quality of life, as well as reduce skeletal-related events. However, safe and optimal duration of bisphosphonates or RANK ligand inhibitors remains unclear in the metastatic breast cancer population. Finally, we will discuss quality measures for delivering end of life care, trends in the country, and methods for improving end of life care with goals of earlier hospice referrals and less treatments at end of life which lead to hospitalizations or ICU stays.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr ES09-3.
Abstract MS01-2: Artificial receptors and the cellular therapy of breast cancer
Authors: Brenner MK 
Published: August 2014

Abstract
It is clear that targeting therapy to the specific molecular lesions of breast cancer affords the best opportunity to obtain effective treatment without adverse effects on normal tissues. The immune system remains one of the most effective targeting systems known, and tumor-directed monoclonal antibodies have already shown significant success in treating this and other malignant disorders. Cellular therapies based on T lymphocytes, by contrast, have not yet made an equivalent impact, even though T cell-based immune responses to tumor have many unique characteristics that should make them highly effective. In this presentation I will discuss one historic success story for cellular immunotherapy -the treatment of EBV-associated lymphoid and epithelial malignancies by tumor specific T cells -and show how the lessons learned from analyzing the mechanisms underlying this success can be implemented to treat other solid tumors including breast cancer Four components are required for effective activity;-. 1) The infused T cells must target strong and unique antigens, presented with ample accessory signals and co-stimulation; 2) The T cells should contain a polyclonal and multispecific memory population directed to tumor; 3) The T cells must be able to overcome potent immune escape mechanisms 4) The environment should favor (homeostatic) lymphoid expansion. We and others are developing a systematic approach to meet these requirements by introducing novel artificial receptors (Chimeric Antigen Receptors – CARs) and other cell engineering components into T lymphocytes. As an increasing level of success becomes documented in hematological malignancy and solid tumors, we can be hopeful that these therapies will become part of the standard of care for breast cancer as well.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr MS01-2.
Abstract OT1-1-08: PERSEPHONE: Duration of trastuzumab with chemotherapy in women with HER-2+ve early breast cancer
Authors: Earl HM , Vallier A-L , Ogburn-Storey E , Cameron DA , Wardley AM , Miles D , Loi S , Hiller L , Higgins HB , Dunn JA 
Published: August 2014

Abstract
Background: PERSEPHONE is a randomised controlled trial comparing six months of trastuzumab to the standard 12 months in patients with HER2 positive early breast cancer. PERSEPHONE is funded by the NIHR HTA programme in the UK.
Methods: 4000 patients (pts) will be randomised into the two arms (1:1). The power calculations assume that the disease-free survival (DFS) of the standard treatment (12 months trastuzumab) is 80% at 4 years. Randomisation of 4000 pts will allow the trial to prove non-inferiority of six months trastuzumab (5% 1-sided significance and 85% power). Non-inferiority is defined as ‘no worse than 3%’ below the control arm (12 month) 4 year DFS. Primary outcome is DFS, and secondary outcomes are overall survival (OS) non-inferiority; cost effectiveness; cardiac function and quality of life. Tumour blocks are collected to research molecular predictors of survival with respect to duration of trastuzumab treatment. Blood samples are analysed for single nucleotide polymorphisms (SNPs) as pharmaco-genetic determinants of prognosis, toxicity and treatment outcome. PHARE, a similar trial from the Institut National du Cancer in France, closed to recruitment in 2010 and presented early data at ESMO 2012. Following this an unplanned interim analysis of PERSEPHONE was presented to the Data Monitoring and Safety Committee (DMSC).
Results: PERSEPHONE commenced recruitment in October 2007. At abstract submission, 2781 pts (70%) had been randomised from 145 UK sites. Recruitment is due to complete in 2015 with the first planned interim analysis of the primary outcome mid-2016. The iDMSC reviewed all data available on HERA and PHARE as well as a PERSEPHONE interim analysis. There were no safety findings or signals that would warrant a change of the study plan and the high quality of data returns was noted.
Conclusion: PERSEPHONE continues the active recruitment phase as planned. Preliminary but inconclusive PHARE data have reinforced interest in the PERSEPHONE trial both nationally and internationally. There has been full support from the Breast International Group (BIG) and the international breast cancer community to answer this important shorter duration question.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr OT1-1-08.
Abstract OT2-3-02: NSABP B-43: A phase III clinical trial to compare trastuzumab (T) given concurrently with radiation therapy (RT) to RT alone for women with HER2+ DCIS resected by lumpectomy (Lx)
Authors: Cobleigh MA , Anderson SJ , Juilan TB , Siziopikou KP , Arthur DW , Rabinovitch RA , Zheng P , Mamounas EP , Wolmark N 
Published: August 2014

Abstract
Background: A significant amount of DCIS is ER negative and/or overexpresses HER2. This provides an opportunity to test targeted therapy in DCIS. In xenograft models and cell lines, T boosts RT effectiveness. In T-treated HER2+ patients, apoptosis occurs within 1 wk of single agent T use, with T found in ductal aspirates. Ample safety evidence for T exists. T given during whole breast irradiation (WBI) may improve results for lumpectomy (Lx) resected HER2+ DCIS. A trial to examine this question will enhance the understanding of breast tumor biology and the prevention of such tumors and could possibly extend breast-conserving surgery benefits for women with DCIS.
Method: After Lx for pure DCIS, each patient's DCIS lesion is centrally tested for HER2 by IHC analysis. HER2 2+ tumors undergo FISH analysis. HER2 3+ or FISH+ patients can be randomly assigned to 2 doses of T, 3 weeks apart during WBI or to WBI alone.
Women ≥18 yrs. with a margin-clear Lx for pure DCIS, with ECOG status 0/1 who are clinically or pathologically node negative are eligible. Centrally tested DCIS must be HER2 +. ER and/or PR status must be known before randomization.
Primary aims are to determine if T decreases ipsilateral breast cancer recurrence, ipsilateral skin cancer recurrence, or ipsilateral DCIS. Secondary aims are to determine the benefit of T in preventing regional or distant recurrence and contralateral invasive breast cancer or DCIS. NSABP B-43 will determine if DFS, recurrence-free interval, and OS can be improved with the use of T. 2000 patients will be accrued over 7.9 yrs, with a definitive analysis of primary endpoints performed at 163 ipsilateral breast cancer events (7.5 - 8 yrs. after protocol initiation) with an 80% power to detect a hazard reduction of 36%, from 1.73 ipsilateral breast cancer events per 100 pt-yrs to 1.11 events per 100 pt-yrs. The 36% observed reduction in the hazard of IIBCR-SCR-DCIS on the T arm is based on a projection of 40% hazard reduction if the compliance were perfect, with a 10% noncompliance rate. As of 5-31-13, 1,349 patients have been randomized.
NCT00769379
Support: PHS NCI-U10-CA-69651, -12027; NCI P30-CA-14599; Genentech, Inc.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr OT2-3-02.
Abstract P1-01-12: Intraoperative detection of sentinel lymph nodes in breast cancer patients using ultrasonography-guided direct indocyanine green dye-marking by real-time virtual sonography constructed with three-dimensional computed tomography-lymphography
Authors: Yamamoto S , Maeda K , Maeda N , Yoshimura K , Oka M 
Published: August 2014

Abstract
Purpose: This study aims to determine the utility of ultrasonography (US)-guided direct dye-marking of sentinel lymph nodes (SLNs) by real-time virtual sonography (RVS) constructed with three-dimensional (3D) computed tomography (CT)-lymphography (LG).
Patients and Methods: We identified SLNs in 258 clinically node-negative breast cancer patients using an RVS system to display in real time a virtual multiplanar reconstruction CT image obtained from CT volume data corresponding to the same cross-sectional image from US. CT volume data were obtained using our original 3D CT-LG, which accurately detects SLNs in breast cancer. We then perform US-guided dye-marking close to SLNs using indocyanine green (ICG). Subsequently, indigo carmine blue dye was injected into the subareolar and peritumoral areas around each primary tumor. All patients underwent SLN biopsy and SLN metastases were examined pathologically.
Results: In all 258 patients, we were able to detect the same SLNs visualized on 3DCT-LG, using the RVS system. We detected ICG close to SLNs in 257 of 258 patients (99.6%) during SLN biopsy. In 25 patients (9%), we failed to follow the blue lymphatic route stained by indigo carmine and SLNs were not stained by indigo carmine, but easily detected SLNs by ICG marking.
Conclusion: US-guided direct ICG dye-marking of SLNs using this RVS system seems useful for the detection of SLNs, allowing easy detection of SLNs even when the stained lymphatic route is not followed.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-01-12.
Abstract P1-01-23: Intraoperative optical coherence tomography for the assessment of metastatic disease in human lymph nodes
Authors: Marjanovic M , Adie SG , Nolan RM , Chaney EJ , Shemonski ND , South FA , Erickson-Bhatt SJ , Shelton RL , Bower AJ , Simpson DG , Ray PS , Cradock KA , Brockenbrough J , Liu G , Boppart SA 
Published: August 2014

Abstract
The status of lymph nodes is an important factor in staging cancer since the transport of primary cancer cells via the lymphatic system is one of the main pathways of metastasis to distant organs. During cancer surgery, lymph node status is evaluated via sentinel lymph node biopsy (SLNB), which involves the removal and analysis of the first (or sentinel) nodes along the lymphatic chain of nodes draining the primary tumor. The sentinel nodes are identified through the accumulation of a radioactive agent (technetium-99) and/or isosulfan blue dye within the nodes, frequently resulting in the resection of multiple nodes for subsequent, often time-consuming, histopathological analysis. The majority of these resected nodes are found by histological analysis to be normal, leading to unnecessary complications, including increased risk of lymphedema. Thus, a method for the in situ assessment of node status could reduce the number of normal lymph nodes that are resected. In this study we evaluated the sensitivity and specificity of three-dimensional optical coherence tomography (OCT) for the intraoperative assessment of metastatic disease in lymph nodes.
OCT is the optical analogue to ultrasound imaging, except images are based on the optical scattering properties of near-infrared light. Real-time OCT with micron-scale resolution affords optical biopsies of tissue for immediate feedback. Intraoperative OCT imaging was conducted on human lymph nodes resected from 49 subjects during breast and, head and neck cancer surgeries. Three-dimensional OCT datasets were recorded ex vivo from one or more locations per node, and marked with surgical ink for subsequent correlation to histology. These lymph nodes then underwent the standard histological processing.
A double-blinded study was performed comparing the assessment of OCT datasets to the co-registered histological findings. Three-dimensional -OCT datasets from 206 sites were independently analyzed by six observers and classified as cancerous or non-cancerous. Seventy-nine sets were identified as unsuitable for OCT analysis due to insufficient nodal tissue within the imaged field-of-view. Early training classification results from three of the six observers resulted in a sensitivity of 64.8% and a specificity of 73.3% for identifying metastatic lymph nodes intraoperatively, in real-time, compared to the gold standard of post-operative histopathology. Final study results are expected to improve with observer training and a decision tree for interpreting OCT images.
Our initial imaging studies of resected lymph nodes in human cancer subjects demonstrate the potential of OCT as a technique for real-time optical biopsy of lymph nodes for the intraoperative staging of cancer.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-01-23.
Abstract P1-04-08: Co-expression of putative stemness and epithelial-to-mesenchymal transition markers on single circulating tumour cells from patients with early and metastatic breast cancer
Authors: Papadaki MA , Agelaki S , Kallergi G , Zafeiriou Z , Theodoropoulos PA , Georgoulias V , Mavroudis D 
Published: August 2014

Abstract
Background: The detection of circulating tumor cells (CTCs) in peripheral blood (PB) of patients with breast cancer (BC) has been associated with poor disease outcome. Cancer cells with stemness and epithelial-to-mesenchymal transition (EMT) properties are considered to display enhanced metastatic potential. The presence of these features in CTCs could be an important determinant of increased metastatic behaviour. A new methodology was developed to investigate the co-expression of the stemness marker ALDH1 and the EMT marker TWIST on CTCs from patients with early and metastatic breast cancer, at the single-cell level.
Patients and Methods : PBMC’ cytospins were prepared from PB obtained from 80 patients with early and 50 with metastatic breast cancer. Triple immunofluorescence staining was performed using anti-pancytokeratin (A45-B/B3), anti-ALDH1 and anti-TWIST antibodies. Classification of ALDH1 expression levels (high or low) and TWIST subcellular localization (nuclear or cytoplasmic) was performed in HepG2 control cells and three representative BC cell lines, using the ARIOL system. A total of 500.000 PBMCs per patient were subsequently analyzed.
Results : CTCs were detected in 13 out of 80 (16%) and in 25 out of 50 (50%) patients with early and metastatic BC, respectively. Although co-expression of ALDH1 and TWIST was observed on almost all CTCs in both patient groups, CTCs expressing the phenotype ALDH1high/TWISTnuclear were more frequently detected among patients with metastatic compared to early disease (76% vs. 15% of patients, p = 0.0004). Moreover, a higher proportion of ALDH1high/TWISTnuclear CTCs was confirmed in the metastatic setting (62% vs. 13% of CTCs, p&lt;0.0001). On the contrary, the phenotype ALDH1low/TWISTcytoplasmic was more prevalent among CTCs detected in early disease (32% vs. 8% of CTCs, p = 0.0006).
Conclusions : A new assay is provided for the evaluation of ALDH1 and TWIST co-expression at the single-CTC level. CTCs bearing the ALDH1high/TWISTnuclear phenotype were more commonly detected in metastatic compared to early BC, suggesting that this phenotype prevails during disease progression. The characterization of CTCs according to these markers could be used to improve risk stratification in BC.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-04-08.