bluuebunny/crossref_metadata_2025_split huggingface dataset:
P3-07-33: Are Single Node Metastases More Common in Patients with Breast Cancer in the Sentinel Node Era?
Authors: Shetty G , Randhawa S , Mohammed I , Harries S , Jones L , Clarke D 
Published: June 2012

Abstract
Background: The axillary recurrence rate after axillary lymph node dissection has been reported as approximately 3%. Since the introduction of sentinel node biopsy (SNB), it has become apparent that, there is a significant decrease in axillary recurrence, ranging from 0.26% to 0.9% in published literature. One of the concerns that arises from this data is that, the sentinel node may have been missed when routine axillary node clearance were being performed. The aim of this study was to compare the results of a cohort of patients who had an axillary staging procedure prior to the introduction of SNB (axillary clearance) with patients after the introduction of SNB in relation to the number who had only one positive node in the axilla.
Methods: From June 2003 to November 2010 data was collected on demographics, histopathology and procedure performed. All patients with invasive breast cancer prior to April 2005 had an axillary node clearance (ANC) with either wide local excision or mastectomy. Since April 2005 all patients with invasive breast cancer had a SNB and patients with a positive sentinel node (SN) underwent ANC. Patients with a negative SNB had no further axillary surgery.
Results: 702 patients had axillary node surgery between June 2003 and November 2010. 251 patients had axillary node clearance (pre SN period) and 451 had SNB (SN period). Average age was 57 years. 509 patients (156 in pre SNB period and 353 in post SNB period) had no nodal metastases. Amongst the 193 node positive patients, 100 had single node involvement. In the pre SNB period 33 (34.7%) patients had single node involvement, compared to 67 (68.3%) in SNB period. The histopathological type of cancer did not vary significantly between the one node positive, multiple node positive and node negative groups.
Conclusion: Our study confirms a significant rise in patients with a single node positive in the sentinel node period. This could be due to the SLN being “missed” during surgery when an axillary node clearance was performed, which would explain the reported higher axillary recurrence rates in the pre sentinel node period compared to the sentinel node period. Another possibility is that the SN is undergoing more detailed histopathological assessment as there are fewer number of lymph nodes to be examined.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-07-33.
P3-07-39: Where To Look for Sentinel Lymph Node in Breast Cancer.
Authors: Düran A 
Published: June 2012

Abstract
Hypothesis: The sentinel Lymph node (SLN) is not only the first extra mammary point of metastatic spread, it also undergoes reactive changes. Sonographically this is evident through an increased width of the hypo-echoic cortex of the lymph node. We examined, if it is possible to localize SLN on sono-morphological features, if it is sonographic detection comparable with the radio nuclide tracer method and if false negative rate (FNR) of SLNB can be reduced by ultrsound.
Method: From 1/2001 to 5/2003, 117 patients with breast cancer where prospectively examined for SLN localization using sonography in addition to radio nuclide -Tc99m- and/or patent blue-methods. The lymph node identified as the SLN in ultrasound was marked using a hook-wire. The sonographic parameters used to identify the SLN were: The node with the widest hypo echoic cortex, located in the caudal axilla and the closest to the glandular tissue and with the greatest diameter.
Results: In all 117 patients, in the region of the caudal axilla, an enlarged, reactive, either tumor free or metastatic SLN could be verified. The location of the SLN was in all cases on the lateral-caudal thoracic wall and consistent with the lymph node group at the lateral border of the pectoralis major. The sonographic detection rate of the SLN was 86%. 70.6% of the sentinel lymph nodes where affected by metastatic spread. In those patients with a pT1a-c-tumor the rate of SLN metastatic spread was 20%. The false negative rate (FNR) for SLN localization with Tc99m/Blau was 10.6 %. Experience has shown that the FNR increases with increasing degree of metastatic spread to the SLN. With the addition of sonography of the axilla the FNR could be decreased to 3.5%.
Sonographic SLN detection rate: 86% ( n=101/117)
False-negative-rate (Blue/Tc) 10.7% (n=6sln- /56N+)
False-negative-rate (Blue/Tc + Sonography) 3.5% (n=2sln-/56N+)
Conclusions: The false-negative-rate of detection of suspected lymph nodes can be reduced using sonographic localization of the SLN. Sonography of the axilla should therefore be an integral part of and standard in the sentinel node-biopsy of breast cancer patients.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-07-39.
P3-07-42: Lymphovascular Invasion Best Correlates with Presence of Nodal Metastasis in Sentinel Lymph Node Biopsy.
Authors: Absar MS , Adelekan MO , Patel E , Cotterill S 
Published: June 2012

Abstract
Background. Sentinel lymph node biopsy (SLNB) biopsy is routinely practised for axillary staging with 25–30% having positive SLN. Tumour size is the most important parameter taken into consideration in decision making in node negative patients with a size cut off for 4–5cm dependant on different units. Lymphovascular invasion (LVI) and Ki-67 a cell-cycle antigen are known important prognostic markers along with the tumour grade, oestrogen receptor and herceptin receptor status.
Aim. To examine whether lymphovascular invasion, Ki-67 or any other factors can be used as a predictor for axillary lymph node involvement and hence prognosis.
METHODS. A prospective study of 264 patients with invasive breast cancer undergoing SLN biopsy between January 2009 and December 2010.
Histopathology reports were reviewed regarding LVI, Ki-67, grade, oestrogen, Progesterone and Herceptin receptor and SLN status. Stats direct was used to analyse data. Logistic regression was used and p-value calculated.
RESULTS. LVI (p value=0.0001) and size(p value=0.0273) were the two most significant factors associated with node positivity. Grade of tumour had a p-value of 0.0825 and Ki67 had a p-value of 0.5217 which were not significant.

DISCUSSION. LVI is the factor which best corelates with presence of metastasis in sentinel lymph node. If this information is available at the time of decision making, it should be strongly considered and pathologists should be encouraged to provide the information. In the absence of LVI, size still remains the best predictor of sentinel lymph node metastasis pre-operatively although consideration of other factors, such as the grade is definitely relevant.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-07-42.
P3-07-44: Feasibility of Axillary Reverse Mapping during Sentinel Lymph Node Biopsy in Breast Cancer.
Authors: Noguchi M , Ohno Y , Nakano Y , Noguchi M , Kosaka T 
Published: June 2012

Abstract
Background: The axillary reverse mapping (ARM) procedure is based on the hypothesis that the lymphatic drainage from the upper arm is different from that of the breast. However, the oncologic safety of the procedure has not yet been determined.
Methods: The ARM nodes were identified using a fluorescence imaging system. Sentinel lymph node (SLN) biopsy was performed in patients with clinically uninvolved nodes. If the SLN was positive, ALND was performed with removal of ARM nodes. Otherwise, the identified ARM nodes were preserved unless they were the same as the SLN.
Results: The ARM node was identified in 30 of 91 patients who underwent SLN biopsy, and it was the same as the SLN in 23 patients. However, in 13 patients with a positive SLN who subsequently underwent ALND, ARM nodes were tumor-free when they were not the same as the positive SLN.
Conclusions: There are limits to the principle of non-overlap between breast and arm nodes. However, it may be feasible to spare ARM nodes during ALND in patients with clinically negative nodes.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-07-44.
P3-09-01: Change in Carbohydrate Intake and Breast Cancer Prognosis.
Authors: Emond JA , Patterson RE , Pierce JP 
Published: June 2012

Abstract
Breast tumors over express insulin-like-growth-factor receptors (IGF-IR), and levels of expression may be inversely related to tumor grade. Dietary factors, particularly carbohydrate intake, may stimulate activation of IGF-1R and affect prognosis.
METHODS: Data are from N=2,651 women in the Women's Healthy Eating and Living (WHEL) Dietary Intervention trial, a plant based intervention trial that did not have a carbohydrate goal. All women were diagnosed with breast cancer within the previous 4 years. Carbohydrate dietary intake data were extracted from multiple 24-hour dietary recalls at study entry and one year, and were compared by recurrence status. Time to recurrence was modeled on year-one change in carbohydrate intake adjusted for baseline intake, menopausal status, and disease, treatment, and study characteristics.
RESULTS: Baseline carbohydrate intake was 233 g/day. Women who recurred had a mean increase in carbohydrate intake over the first year, compared to those who did not recur (2.3 vs. −2.7 g/day; p=0.188). Change in starch intakes accounted for 48% of the change in carbohydrate intake (R-squared: 48%; p&lt;0.001). Baseline starch intake did not differ by recurrence status (95.8 g/day; p=0.219). Mean year-one change in starch intake was −4.1 g/day among women who recurred vs. −8.7 g/day among women who did not recur (p=0.015). Year-one change in starch intake was independent of the study intervention (p=0.326). In the adjusted model, a 5-g/day increase in starch related to a 3% increased risk of recurrence (HR=1.03; 95% CI 1.01 - 1.06; p=0.017). The increased risk was limited to women diagnosed with low grade tumors (Table 1).

DISCUSSION: Dietary modifications targeting starch intake warrant further investigation as a preventive measure against breast cancer recurrence.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-09-01.
P3-10-03: Bardoxolone (5MeCDDO) Inhibits Cancer Initiation but Promotes Progression in Rodent Models of Breast Cancer. What Does It Mean for the Antioxidant Response Element (ARE) as a Primary Prevention Target?
Authors: Lubet RA , Townsend R , Vedell P , Steele VE , Grubbs CJ 
Published: June 2012

Abstract
The preventive efficacies of the triterprenoid 5MeCDDO were examined in three preclinical models of breast cancer. We initially evaluated 5MeCDDO in an ER+ mammary model in which female Sprague-Dawley rats were administered MNU, i.v., at 50 days of age. 5MeCDDO (27 ppm) was administered in the diet beginning 5 days after MNU, and continuing for the duration of the study. Doses &gt;50 ppm were toxic. 5MeCDDO failed to decrease tumor latency or multiplicity and, in fact, increased the size of the cancers which did develop. This concentration of 5MeCDDO greatly increased liver to body weight ratios. We also examined the preventive efficacy of 5MeCDDO (54 and 27 mg/kg diet) in a bitransgenic model (MMTV-Neu/p53KO) of ER− mammary cancer. In this model, animals develop cancers which overexpress Neu and fail to have a mutation in the transmembrane domain of Neu. Similarly to results in the MNU model, 5 MeCDDO did not alter either tumor latency or multiplicity. The effect of 5MeCDDO was further evaluated in a third model in which ER+ tumors were induced by the procarcinogen dimethylbenzanthracene (DMBA). DMBA was administered by gavage to female Sprague-Dawley rats at 50 days of age. In this model (which examines the ability of an agent to alter the activation of the carcinogen) the preventive agent was administered beginning 7 days prior to DMBA and was continued until 7 days post DMBA. 5,6 Benzoflavone (500 ppm), a positive control, decreased tumor multiplicity &gt;90%, while 5MeCDDO (27 or 2.7 ppm) decreased multiplicity 65 and 35%, respectively. The efficacy observed in this model is in agreement with the ability of the agent to stimulate the ARE, and to induce a variety of ARE related genes (e.g., GST PI, quinone reductase, etc). Thus, as expected, high induction of the ARE was associated with a decrease in DMBA-induced cancer initiation, but not a decrease in the progression stage of mammary cancer development in three cancer models. This latter finding brings into question whether merely measuring induction of the ARE (e.g., quinone reductase) is sufficient to imply the general preventive efficacy of a given agent or mixture. Supported by NCI contract number HHSN261200433001C.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-10-03.
P3-11-07: Mammary Gland Biopsy To Examine Surrogate Endpoint Biomarkers of Preventive Agent Efficacy.
Authors: Heckman-Stoddard B , Lubet RA , Bode AM , Grubbs CJ 
Published: June 2012

Abstract
Phase II breast cancer prevention trials examine agent activity by sampling and imaging the breast through core needle biopsy, fine needle aspiration, or imaging (e.g., mammography). The biomarker endpoints in normal or at risk breast tissue employed with biopsies or fine needle aspirates (e.g., Ki67 or apoptosis) have often not been formally validated relative to a tumor endpoint. In this study, we have attempted to examine these endpoints in a preclinical model for which we have final tumor data. In the methylnitrosourea (MNU)-induced rat mammary cancer model, estrogen receptor positive cancers develop that are histologically similar to a large majority of human tumors. Here we present a protocol for correlating surrogate endpoint biomarkers and agent efficacy in the same animal. Biopsy samples are taken of the normal mammary gland after MNU treatment, and a week later the animals are started on the preventive agent. After 2 weeks, a second biopsy is taken and the animals are followed for tumor development. To test the protocol, we examined surrogate endpoints of tamoxifen efficacy at human equivalent dosages (5mg/d and 20mg/d). Both doses of tamoxifen prevented the development of tumors in the MNU-treated rats. The pre/post biopsy analysis revealed a statistically significant reduction in Ki-67 consistent with the clinical trial data. Additional biomarkers of apoptosis and the chromosome condensation pathway will be presented.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-11-07.
P3-14-16: Molecular Phenotype and the Use of HER-2 Targeted Agents Influence the Accuracy of Breast MRI after Neoadjuvant Chemotherapy.
Authors: Moon H-G , Han W , Noh D-Y , Ahn S , Kim J , Shin H , Min J 
Published: June 2012

Abstract
Background: Improved understanding of factors affecting the accuracy of breast magnetic resonance imaging (MRI) after neoadjuvant systemic therapy (NST) can lead to more tailored use of MRI in deciding surgical extent after NST.
Materials and Methods: We analyzed the imaging and clinicopathologic data of 463 patients who underwent NST. We aimed to investigate whether the molecular subtypes, as well as the use of targeted therapies, were associated with changes in the accuracy of MRI predicting residual tumor extent.
Results: The accuracy of MRI predicting the residual tumor extent was most accurate in triple negative breast cancer and was least accurate in Luminal A subtype (Pearson's correlation coefficient of 0.754 and 0.531, respectively). Multivariate analysis suggested estrogen receptor status as an independent factor influencing the MRI accuracy. In HER2−amplified tumors, the use of HER2−targeted agents was associated with less accurate MRI prediction. Dual HER2−blockade by using trastuzumab and pertuzumab resulted in lowest MRI accuracy among the patients treated with HER2−targeted agents.
Conclusion: The accuracy of MRI in predicting residual tumor extent was lowest in ER positive tumors treated with NST. In HER2 positive tumors, the use of HER2−targeted agents resulted in less accurate MRI after NST.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-14-16.
P3-17-05: Beyond HER2 and Hormonal Agents: The Heat Shock Protein 90 Inhibitor Ganetespib as a Potential New Breast Cancer Therapy.
Authors: Friedland JC , Sang J , Modi S , Bradley R , El-Hariry I , Wada Y , Proia DA 
Published: June 2012

Abstract
Background: Ganetespib is a fully synthetic and selective inhibitor of heat shock protein 90 (HSP90), a molecular chaperone recognized as a key facilitator of breast cancer initiation, progression and metastasis.
Methods: Preclinical activity of ganetespib across the four major breast cancer subtypes and inflammatory breast cancer was assessed in vitro and in vivo. Modulation of cell proliferation and viability was determined both in monolayer and three-dimensional cultures. HSP90 client protein expression and activity was monitored by Western blot and protein array. To recapitulate clinical dosing, kinetics of client protein destabilization were measured following short exposures to drug in vitro. Anticancer activity of ganetespib was further investigated in vivo using breast cancer xenografts.
Results: Ganetespib displayed potent, low nanomolar activity in luminal (A and B), basal (A and B) and inflammatory breast cancer cell lines grown as monolayers in vitro. BT-474 (HER2 amplified) luminal cells grown as mammospheres in 3D were equally as sensitive to ganetespib as those grown in monolayer. In luminal cells, ganetespib simultaneously disrupted multiple signaling components including the estrogen and progesterone receptor, several receptor and non-receptor tyrosine kinases, as well as the MAPK pathway. Further, ganetespib effectively inhibited AKT, PDK1 and SGK3 activity in PIK3CA mutant cells suggesting that HSP90 is essential for both AKT-dependent and AKT-independent signaling. Clinically relevant exposure times to ganetespib in vitro resulted in potent, long term destabilization of HER2. In the basal-like breast cancer cell line MDA-MB-231, enriched in CD44+CD24- stem like cells that commonly display chemotherapeutic resistance and activated JAK2/STAT3 signaling, ganetespib (50 nM) induced significant degradation of JAK2 concordant with loss of both tyrosine and serine phosphorylation of STAT3, followed by cell death. The potent anticancer activity in vitro translated in vivo, where ganetespib was effective in modulating breast cancer xenograft growth as a single agent in both luminal and basal-like breast cancer models. Finally, ganetespib has demonstrated encouraging signs of clinical activity in breast cancer patients, including confirmed partial responses in both a triple negative breast cancer patient and a HER2 positive breast cancer patient.
Conclusions: Ganetespib is a highly potent HSP90 inhibitor that displays preclinical activity in breast cancer due to its ability to simultaneously perturb multiple oncogenic signaling pathways.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-17-05.
P3-17-10: EpCAM as a Target for Chemical Antibodies in Metastatic Breast Cancer.
Authors: Shigdar SL , Duan W 
Published: June 2012

Abstract
EpCAM is a 40kDa glycoprotein that functions as an adhesion molecule in benign epithelium. However, it is over-expressed in nearly all carcinomas, including breast carcinomas, and has been implicated in the pathogenesis and progression of cancer. In primary breast carcinoma, its over-expression correlates with a diminished overall survival in patients with node-positive disease. Indeed, recent evidence has shown that EpCAM is expressed at a higher level in metastases than in matched primary breast carcinoma. This has led to the suggestion that EpCAM over-expression is associated with aggressive behaviour, and that it could be considered a promising therapeutic target for breast cancer. Several immunotherapy trials are ongoing, though there are limitations to their delivery and distribution, suggesting a smaller and more effective EpCAM targeting molecule is required.
Aptamers, also known as chemical antibodies, are short-stranded DNA or RNA molecules and are selected via the systematic evolution of ligands by exponential enrichment (SELEX). They are 10 to 20 times smaller than antibodies and exhibit superb tissue penetration, thereby indicating their suitability in cancer targeting. In addition, aptamers are more stable, non-immunogenic and non-toxic. Following 12 rounds of SELEX using EpCAM protein as a target, we generated several EpCAM specific RNA aptamers. These were investigated using flow cytometry and confocal microscopy for their ability to bind to three breast cancer cell lines, MCF-7, T47D and MDA-MB-231. Our 19-nt aptamer showed specific binding to all three cell lines. In addition, it also showed superior penetration of breast cancer 3-D spheroid tumor models, as compared to a control aptamer and negative cell lines. This aptamer has also shown efficient internalisation via receptor-mediated endocytosis, suggesting it to be a suitable targeting moiety for drug delivery to both primary and metastatic tumors. The usefulness of this aptamer in clinical applications is being actively investigated.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-17-10.
P3-18-07: Multiplex RTK Inhibitor Screening Utilizing a Plate-Based Immunoassay with Near-Infrared Detection.
Authors: Finkel DJ , James AE , Felix RA , Wegner GJ 
Published: June 2012

Abstract
Receptor-tyrosine kinases (RTKs) are transmembrane proteins that have been implicated in various cancers and are considered therapeutic targets. The phosphorylation of RTKs on tyrosine residues leads to their activation. We have previously used the Proteome Profiler™ 96 Human Phospho-RTK Antibody Array, a plate-based multiplex immunoassay, to determine the phospho-tyrosine profile of RTKs in MDA-MB-453 breast cancer cells. Most notably, the ErbB family of RTKs were shown to be hyperactivated in this cell line. In this study, we use the same multiplex assay to screen a small molecule kinase inhibitor library (TOCRIS, Catalog # 3514) to identify inhibitors with selectivity towards the ErbB receptors. MDA-MB-453 cells were treated with the kinase inhibitor library prior to treatment with ligands to stimulate ErbB receptor tyrosine phosphorylation and subsequently lysed. The lysates were analyzed with the Proteome Profiler 96 Human Phospho-RTK Antibody Array using near-infrared fluorescent detection. Ligand-dependent tyrosine phosphorylation of all four ErbB receptors was monitored simultaneously and the effects of different kinase inhibitors were determined. While several known ErbB inhibitors blocked ErbB phosphorylation, our screen also identified several inhibitors reported to be selective for other kinases that effectively inhibited ErbB activation. The activation of ErbB2 was selectively inhibited by NH 125, GF 109203X, SB 202190, SB 216763, and ZM 306416 hydrochloride. The results obtained with this multiplex assay were confirmed by singleplex ELISA for ErbB receptors. Hence, the data collected with our multiplex assay provides a rapid method for the analysis of inhibitor effects on a defined signaling pathway. This may facilitate a faster identification of selective kinase inhibitors that have therapeutic potential for treating ErbB-overexpressing cancers.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-18-07.