bluuebunny/crossref_metadata_2025_split huggingface dataset:
Six month follow up on a series of patients treated with an electronic brachytherapy technique for intracavitary accelerated partial breast irradiation.
Authors: Mehta V , Griem KL , Haile KL , Stevens R , Syzek L , Elliott K 
Published: December 2010

Abstract
Abstract #5149
Purpose: Phase IV prospective post market study to evaluate the safety and device performance of electronic brachytherapy treatment using the Xoft Axxent System as adjuvant therapy for early stage breast cancer.&#x2028; Methods and Materials: 44 patients were enrolled between April 2007 and March 2008, and 13 patients have completed 6 months of follow up to date. Patients were eligible if they were older than 50 years, had completely resected DCIS (&lt;2.0cm) or invasive ductal carcinoma (&lt;2.0cm), and microscopic surgical margins of at least 1mm. The balloon applicator was placed in a closed cavity and a balloon surface to skin distance of at least 7mm was required for treatment. The radiation treatment (RT) consisted of delivering 3.4 Gy/fraction twice a day for 10 total fractions. The primary endpoint was the successful delivery of the prescribed RT. Secondary endpoint was adverse device related events.&#x2028; Results: Thirteen of the forty-four patients that were enrolled and treated on this study have been followed a minimum of 6 months. The three month follow-up included cosmesis evaluation using the Harvard Cosmesis Scale, and adverse events. The three month cosmesis evaluated by physicians' showed 100% of the patients rated with excellent to good cosmesis. Related adverse events reported through three months included a total of fifteen CTC v3 Grade One AEs. Events included erythema, itching, induration, skin firmness, rash/ desquamation, fatigue. Of these events 90% were resolved. The six month cosmesis physician evaluations showed 82% of the patients had excellent to good cosmesis. Twelve of the 13 patients rated the appearance of their breast, in addition to the physician assessment, and 12 out of 12 rated their appearance good to excellent, one patient did not select any rating. Adverse events reported at six months were a total of three new CTC v3 Grade One. These AEs included occurrences of induration, skin firmness, and hyperpigmentation. A patient satisfaction survey at 6 months follow-up was completed by the patients. Certain survey questions required an answer using a scale of 0-6 for the ratings, where six was the best score. The patients' mean overall rating of satisfaction with the study participation was 5.55 out of 6 (min 3, max 6), satisfied with the radiation treatment was rated 5.54 out of 6 (min 3, max 6). All 13 patients, 100%, stated they would recommend this treatment to a friend.&#x2028; Conclusion: This report provides an early look at the experience of using electronic brachytherapy as a means for intracavitary partial breast radiotherapy. The first cohort has reached a minimum of 6 months of follow up and the results appear promising. Additional patient follow up will be presented at the meeting.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5149.
Objective cosmetic analyses after breast surgery with the breast analysing tool (BAT) correlates with subjective and objective scores: a new tool for prospective trials.
Authors: Krois W , Riedl O , Dubsky P , Jakesz R , Gnant M , Wild T , Fitzal F 
Published: December 2010

Abstract
Abstract #5150
Objective: Objective cosmetic analyses are important to reproducibly evaluate cosmetic outcome after oncoplastic surgery, breast conserving surgery or new radiotherapy methods such as partial breast irradiation. We developed a new objective scoring software, the breast analysing tool (BAT), to measure cosmesis using a single frontal picture. Method: Images from 129 breast cancer patients after breast conserving therapy and radiotherapy were analysed with the software. Distances from the breast border to the nipple, from the Jugulum to the nipple and the breast circumference of one breast was subtracted from the other. The difference in pixels transferred to a breast symmetry index (BSI) by using a mathematic formula. This results in a BSI ranging between 0 (excellent cosmesis) and 11 (bad cosmesis). The results were correlated with the subjective Harris scale ranging from 1-4 (excellent, good, fair and poor cosmesis) and another objective tool, the breast cancer conserving treatment cosmetic result (bcct.core) software. Subjective analyses were done by students (n=4), surgeons (n=10) and experts in breast surgery (n=2) as well as by international experts using a Delphi procedure (n=13). Results: All subjective scores significantly (p&lt;0.05) correlated with the BAT score with a Pearson correlation coefficient of 0.719 (students), 0.697 (surgeons), 0.760 (experts local) and 0.60 (experts international). There was also a significant correlation between the bcct.core and the BAT software with a correlation coefficient of 0.581.&#x2028; &#x2028; Conclusion: The BAT software is ready to be used for prospective and retrospective trials in local breast cancer therapy.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5150.
Ipsilateral breast tumor recurrence rates in breast cancer patients treated with preoperative chemotherapy, breast conserving surgery and intraoperative radiotherapy with electrons.
Authors: Reitsamer R , Sedlmayer F , Menzel C , Glueck S , Kopp M , Peintinger F 
Published: December 2010

Abstract
Abstract #5156
Introduction: Ipsilateral breast tumor recurrence (IBTR) rates are reported to be increased in patients treated with breast conserving surgery after preoperative chemotherapy. Aim of this study was to evaluate the IBTR rate in patients who were treated with preoperative chemotherapy followed by breast conserving surgery and intraoperative radiotherapy with electrons (IOERT).&#x2028; Patients and Methods: 84 patients with clinical stage II or III breast cancer were included in the study. Patients received 3 to 6 cycles of anthracyclin/taxane containing preoperative chemotherapy. All patients had breast conserving surgery with sentinel node biopsy and axillary lymph node dissection and received intraoperative radiotherapy with 9 Gy to the 90% reference isodose as an anticipated boost radiation. Whole breast radiotherapy (WBRT) was performed after surgery for all patients.&#x2028; Results: Pathologic complete response was achieved in 18/84 (21%) patients. Mean resection volume was 250 ml. After a median follow-up of 30.5 months (range 6 – 77 months) no IBTR could be observed. One patient developed a locoregional recurrence in the axilla and nine patients developed distant disease, five of those died of disease. Three patients developed contralateral breast cancer. 71 patients are alive without evidence of disease.&#x2028; Conclusion: Breast conserving surgery with IOERT in boost modality after preoperative chemotherapy is a reliable tool for the prevention of IBTR. The period between IOERT and WBRT is short as no adjuvant chemotherapy is necessary. Cosmetic outcome is excellent.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5156.
Pharmacogenetic (CYP2D6) and gene expression profiles (HOXB13/IL17BR and molecular grade index) for prediction of adjuvant endocrine therapy benefit in the ABCSG 8 trial.
Authors: Goetz M , Ames M , Gnant M , Filpits M , Jakesz R , Greil R , Marth C , Samonigg H , Suman V , Safgren S , Kuffel M , Weinshilboum R , Erlander M , Ma X , Ingle J 
Published: December 2010

Abstract
Abstract #57
Background: ABCSG 8 is the only prospective trial examining the value of switching patients (pts) to an aromatase inhibitor after tamoxifen (Tam) in which randomization occurred prior to therapy. This trial demonstrated that 2 years (yrs) of Tam followed by 3 yrs of anastrozole (TAM to A) was superior to 5 yrs of Tam (Jakesz SABC 2005). Tam is metabolically activated by CYP2D6 to endoxifen and pts with impaired CYP2D6 metabolism have a higher risk of recurrence (Goetz JCO 2005). The HOXB13/IL17BR (H/I) index (Ma Cancer Cell 2004) is associated with Tam resistance while a 5-gene molecular grade index (MGI) distinguishes outcome in grade II tumors. H/I and MGI are complementary prognostic factors that define low (low MGI), intermediate (low H/I, high MGI) and high risk groups (high H/I and MGI) (Ma Clin Cancer Res 2008). We sought to validate these biomarkers in ABCSG Trial 8, and hypothesized that they may predict the benefit of sequencing TAM to A versus Tam alone.&#x2028; Methods: From 1996-2004, ABCSG 8 randomized 3,901 pts with ER positive breast cancer. The primary endpoint was event-free survival. Assuming 40% of pts had reduced CYP2D6 metabolism, we designed a nested case control study in which 110 Tam treated cases matched to 2 controls would yield 80% power to detect a relative risk of 2.3 for pts with reduced CYP2D6 metabolism. Additionally, we sought to perform an exploratory analysis of the benefit of switching from Tam to A in pts with impaired vs non-impaired CYP2D6 metabolism. DNA and RNA derived from paraffin embedded sections were used to genotype for CYP2D6 and to obtain H/I and MGI RT-PCR profiles.&#x2028; Findings: Thus far, CYP2D6 genotyping is complete in 345 pts corresponding to 53 cases/106 controls (Tam) and 62 cases/124 controls (Tam to A). DNA and RNA yields were excellent with a CYP2D6 genotype call rate of &gt;95%. CYP2D6 allele frequencies were as expected: *3 (.01), *4, (.23), *6 (.01), *10 (.02), *17 (.00), and *41 (.10). 44% of pts had reduced CYP2D6 metabolism (at least one CYP2D6 null allele or intermediate metabolizer) and 8% were CYP2D6 poor metabolizers. For H/I and MGI, 340 pts were profiled with 64%, 20% and 16% in the low, intermediate, and high risk groups, respectively. Tissue sectioning/genotyping for additional cases/controls is ongoing.&#x2028; Discussion: This is the first retrospective analysis of a large Tam versus Tam to A trial to evaluate the association between 1) CYP2D6, HOXB13/IL17BR, and MGI with TAM treatment outcome and 2) the predictive benefit of these biomarkers in pts randomized to switch from Tam to AI versus Tam alone. Final results will be presented at the meeting.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 57.
Molecular targeting of HER2 for diagnosis and therapy of breast cancer.
Authors: Capala J , Kramer-Marek G , Lee S , Hassan M , Kiesewetter DO , Puri A , Chernomordik V , Gandjbakhche A , Griffiths G , Blumenthal R 
Published: December 2010

Abstract
Abstract #6004
Background: Expression of HER2 receptors in breast cancer is correlated with poor prognosis and may be different in distant metastases as compared to the primary tumor. We are developing methods to assess global expression of HER2 in vivo and to deliver therapeutic agents specifically to HER2-positve cells.&#x2028; Materials and Methods: As the targeting agent we use an Affibody molecule (http://www.affibody.com). These very stable and highly soluble proteins are relatively small (8.3 kDa) and bind to HER2 receptors with high affinity (22 pM). For imaging with PET, SPECT, or optical methods, an appropriate group containing the imaging beacon can be attached by a selective chemical reaction to a unique C-terminal cysteine residue of Affibody. For therapeutic purposes, they can be conjugated to multifunctional nanoparticles containing both imaging and therapeutic agents. We have conjugated affibody molecules with thermo-sensitive liposomes or gold nanoparticles (subsequently activated with neutrons) and characterized their biodistribution using optical imaging and SPECT, respectively. We used PET imaging with 18F-ZHER2-Affibody to monitor the down-regulation of HER2 following four doses (50 mg/kg) of 17-dimethylaminoethylamino-17-demethoxy-geldanamycin, 17-DMAG, an inhibitor of Hsp90 known to decrease HER2 expression. Animals were scanned before and after treatment. Immediately after the last scan, the mice were euthanized and tumors were frozen for ex-vivo analysis of receptor expression. For optical imaging, we used AlexaFluor dyes conjugated with affibody molecules containing an albumin binding domain that extended their circulation time. We have attached nanoparticles (liposomes and gold) to Affibody molecules using the same type of maleimide chemistry.&#x2028; Results: Our results showed that Affibody molecules do not affect the targeted cells and that their binding does not interfere with either the binding or the effectiveness of trastuzumab. 18F-ZHER2-Affibody was eliminated quickly from blood and normal tissues, providing high tumor/blood and tumor/muscle ratios by 1h post injection. The signal obtained from PET and optical imaging correlated well with the number of receptors expressed in the studied tumors as assessed by western blot, ELISA, and IHC. Following 17-DMAG treatment, the level of HER2 expression, estimated by PET imaging, in BT474 and Mcf-7/clone18 tumors decreased 70% and 30%. This change was confirmed by the biodistribution studies, ELISA and western blot.&#x2028; Discussion: This strategy, involving assessment of target presence and distribution in an individual patient followed by optimized, target-specific drug delivery, may significantly improve efficacy of breast cancer treatment while reducing side effects.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6004.
Multi-modality imaging of N-methyl-N-nitrosourea-induced mammary tumors by MRI and small animal PET.
Authors: Shoghi KI , He J , Su Y , Yan Y , Rowland D , Garbow J , Mach RH , Lubet RA , You M 
Published: December 2010

Abstract
Abstract #6008
Background: We evaluated the use of high resolution Magnetic Resonance Imaging (MRI) and small animal Positron Emission Tomography (PET) imaging in assessing tumor proliferation and response to therapy in N-methyl-N-nitrosourea (MNU)-induced mammary tumors.&#x2028; Materials and Methods: The study comprised of 30 untreated MNU rats, 6 Targretin-treated MNU rats, and 6 Vorozole-treated MNU rats. Rats received a baseline imaging session when they developed their first palpable mammary tumor and were subsequently randomized into a control group or a treatment group with either Targretin (220mg/kg in the diet) or Vorozole (1.25mg/kg body weight by gavage). Treatment lasted for 8 weeks following the baseline imaging session. Each rat was imaged for 10-weeks at 2-week intervals with a) FDG to assess the metabolic state of tumors, b) MRI to monitor tumor volume, and c) [18F]ISO-1, a Sigma-2 radiolabeled ligand, to assess the proliferative status of MNU-induced tumors. Static images (10-minute) were obtained 60-minutes post-injection of FDG and [18F]ISO-1. In untreated tumors, a minimum of 40 PET outcome measures were assessed for their ability to predict changes in MRI-derived volume measurements between consecutive imaging sessions. In addition, regression analysis was performed to assess the correlation (R) between the measures. In treated tumors, the time-course of changes in PET outcome measures relative to baseline was evaluated to assess the efficacy of Targretin and Vorozole, in particular in characterizing short-term response (initial 2-weeks) and response to treatment withdrawal (weeks 8-10).&#x2028; Results: An index characterizing a MRI-normalized [18F]ISO-1 uptake significantly correlated (R=0.7, P&lt;0.0003) with changes in tumor volume between consecutive imaging sessions in untreated tumors. In contrast, there was no correlation between FDG outcome measures and changes in tumor volume. Targretin had the strongest short-term efficacy with a reduction in tumor load, on average, by as much as 60% compared with Vorozole's 20% reduction in tumor load. We observed higher rate of tumor resurgence in rats treated with Vorozole compared with Targretin, suggesting a residual effect of Targretin. In general, PET outcome measures of both FDG and [18F]ISO-1 delineated short-term response to treatment and non-responding tumors. [18F]ISO-1 was more sensitive than FDG in capturing tumor growth following treatment withdrawal at week 8.&#x2028; Conclusion: MRI and small animal PET provide a platform to assess MNU-induced tumor proliferation and the efficacy of therapeutic interventions non-invasively, as demonstrated in this work.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6008.
Prognostic and predictive value of enzymes of the sphingolipid metabolism in breast cancer.
Authors: Ruckhäberle E , Rody A , Gaetje R , Engels K , Holtrich U , Karn T , Kaufmann M 
Published: December 2010

Abstract
Abstract #6014
Backround:&#x2028; Sphingolipids do not only have structural roles for the cell membrane, but also act as effector molecules and second messengers in signal transduction with links to cancer initiation, progression and treatment response. Knowledge of sphingolipid's impact on breast cancer and its prognosis is limited to in vitro data. Clinical data is rare but needed.&#x2028; Material and Methods: We analyzed gene expression of 43 proteins from the sphingolipid pathways in different subtypes of breast cancer using microarray data of 1269 tumor samples (test set n=171; validation sets n=1098). Kaplan Meier analysis of disease free survival was performed to examine the prognostic value of different markers. In addition immunohistochemistry was done to determine whether the genes of the sphingolipid rheostat are expressed in cancer or stroma cells of the tumor.&#x2028; Results: Significant relationships of several genes of the sphingolipid metabolism with clinical parameters were obtained. Sphingosine kinase 1 (SPHK1), ceramide galactosyltransferase (UGT8), and Ganglioside GD3-Synthase (ST8SIA1) displayed higher expression among ER negative tumors. In contrast, glucosylceramidesynthase (GCS), dihydroceramidesynthases (LASS4, LASS 6) and acid ceramidase (ASAH1) were higher expressed in ER positive samples. Survival analysis revealed a significant worse outcome of patients with high SPHK1 expression. LASS 6 and GCS gene expression had no prognostic impact when the estrogen receptor status was taken into account in multivariate analyses. Immunohistochemistry identified the carcinoma cells as the major source of SPHK1 expression in the tumor.&#x2028; Conclusions: These studies of a large cohort of clinical breast cancer samples reveal that sphingolipids do play a role in breast cancer. Enzymes of the sphingolipid metabolism have impact on the prognosis of breast cancer patients and targeting the sphingolipid rheostat can open new treatment options.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6014.
Notch-1 activates ErbB-2 through a PEA3-dependent mechansim.
Authors: Clementz AG , Osipo C 
Published: December 2010

Abstract
Abstract #6015
Over-expression or gene amplification of ErbB-2 occurs in 25% of breast cancer which is associated with malignancy, poor overall survival, and resistance to some anti-hormonal therapies. Although trastuzumab has had a tremondous impact on survival, resistance results within the first year of treatment in 15% of cases and remains a major problem in the metastatic setting. We have recently published (Osipo et al., 2008. Oncogene) that the expression and activity of Notch-1, a potent breast oncogene and cell fate determinant is increased in ErbB-2 positive breast cancer cells in response to trastuzumab. Furthermore, we have shown that Notch-1 might contribute to trastuzumab resistance. In the current study, we asked whether Notch-1 could activate ErbB-2. Results demonstrated that a Notch inhibitor, γ-secretase inhibitor (GSI) or a Notch-1 siRNA decreased tyrosine phosphorylated and total ErbB-2 expression in SKBR3, MCF-7, and MDA-MB-231 cells. Furthermore, overexpression of constitutively active Notch-1 increased tyrosine phosphorylated ErbB-2 and reversed the inhibition by a GSI. ErbB-2 promoter activity using a luciferase reporter construct was decreased by Notch-1 siRNA only when the PEA3 Ets binding site was mutated. These results suggest that Notch-1 is an activator of ErbB-2 in breast cancer cells that express low or inactive PEA3.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6015.
Involvement of notch and RUNX pathways in human breast cancer.
Authors: Yong T , Meyers S , Davis N , Sun A 
Published: December 2010

Abstract
Abstract #6021
Background: Recent studies have demonstrated that the Notch signaling and the RUNX-mediated transcription pathways converge in mammalian hematopoiesis where they regulate proliferation and development. Evidence from in vitro experiments, mouse models and human tumors demonstrate that Notch signaling plays an oncogenic role in human breast cancer. Studies of RUNX factors involvement in human breast cancer suggest that the Core Binding Factor [CBF, a heterodimeric transcription factor composed of a RUNX DNA binding protein (RUNX1, RUNX2, or RUNX3) and a single non-DNA binding component termed CBFβ] participates in regulating the malignant phenotype of the tumor. Thus, the RUNX factors are primarily important to Notch signaling, and it seems likely that Notch:RUNX cross-talk will be important to cellular function and disease in a variety of tissue types. Here, we present our findings on cross-talk between Notch and RUNX pathways, which will lead to a better understanding of Notch and RUNX regulated transcription in breast carcinogenesis.&#x2028; Material and Methods: The expression and localization of the Notch1 NICD and RUNX2 in normal breast tissue and breast tumor were determined by immunohistochemistry on human breast tissue microarray obtained from Feist-Weiller Cancer Center. The expression profiles of Notch and RUNX were evaluated by real-time RT-PCR, Western Immunoblot, and electrophoretic mobility shift assay (EMSA).&#x2028; Results and Discussion: We found activated Notch1 and RUNX2 predominantly expressed in the cytoplasm and nucleus of cells in human normal breast tissues, respectively. However, in human breast cancer tissue samples, activated Notch1 was found in the nucleus in a high proportion of the cancer cells, while RUNX2 presence in the nucleus was much reduced and this could be due to mislocalization, over-expression or delayed degradation of the proteins. The major transcript in the breast cancer cell lines is RUNX1, but by EMSA, RUNX2 factor is the predominant biologically active and functional form of RUNX factors associated with breast cancer cell line-derived CBF. Transcript degradation and protein stability may play significant role in the regulation of RUNX factors in breast carcinogenesis. Down-regulation of CBFβ was found to affect Notch signaling in breast cancer cells and this may lead to the identification of new therapeutic targets for the successful treatment of breast cancer.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6021.