bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase I study of an autologous GM-CSF-secreting breast cancer vaccine.
Authors: Anderson KS , Hodi FS , Sasada T , Canning C , Hassett M , Mayer E , Hannagan K , Wong J , Colson Y , Shoji B , Najita J , Sibani S , LaBaer J , Winer EP , Dranoff G 
Published: December 2010

Abstract
Abstract #4124
Background: Vaccination with tumor cells engineered to secrete granulocyte-macrophage colony stimulating factor (GM-CSF) generates potent, specific, and long-lasting anti-tumor immunity in multiple tumor models. At DF/HCC, over 100 patients with melanoma, ovarian cancer, and lung cancer have been vaccinated. These studies have led to the identification of targets of immune-mediated tumor destruction. Here, we present analysis on the safety, feasibility, and biologic activity of an autologous GM-CSF-secreting breast cancer vaccine.&#x2028; Methods:27 patients with metastatic breast cancer have undergone tumor procurement for vaccine from malignant pleural effusions (23), ascites (1), tumor nodules (2), lymph node (1), and 12 patients have received vaccine. Cells were transduced with a replication defective adenoviral vector encoding GM-CSF, irradiated, and GM-CSF secretion was measured by ELISA. Patients were required to have received at least one prior chemotherapy for metastatic disease and have an ECOG performance status 0-1. Vaccine was delivered s.c. and i.d. weekly for three weeks, then every other week. Immune monitoring included skin biopsies of vaccine sites, measurement of leukocyte populations, and proteomic-based assessment of antibody responses.&#x2028; Results: Sufficient viable tumor cell yields for vaccination were obtained from all patients, with cellular yields ranging from 1.1-679 x 106 cells and viabilities ranging from 71-100%. Dose levels were based on cellular yield, ranging from 105 -107 cells/dose. The average yield of GM-CSF was 838 ng/106 cells/24 hrs (range: 24.4-5696), higher than the average yields for lung cancer and melanoma. Vaccinated patients were 34-69 years, and received 3-23 vaccines. 9 patients had progressive disease after 3-10 vaccines (1-4 months). One patient had stable disease after 23 vaccines (11 months), resumed vaccination at 16 months for progression and remains on study. One other patient remains on study, and one patient did not have measurable disease. Toxicities related to treatment include grade I/II local injection-site reactions, grade I/II inflammation at tumor sites as well as grade I/II fatigue, fever, nausea, and edema. Skin biopsies of vaccination sites revealed mild-moderate infiltration of lymphocytes, granulocytes, and macrophages.&#x2028; Conclusion: Breast cancer cells can be harvested in sufficient number for autologous vaccine production from solid tumor as well as from malignant effusions. Autologous vaccination can induce coordinated immune responses with limited toxicity. The proteomic-based identification of antigen-specific immune responses following vaccination will be presented.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4124.
Hermodulins: bispecific ligand traps inhibit breast tumor growth and metastasis.
Authors: Turin L , Beryt M , Zhang J , Brdlik C , Jin P , Huang J , Bai X , Shepard H 
Published: December 2010

Abstract
Abstract #4127
Signalling by the human EGF (HER) receptor family can induce tumorigenicity and metastasis of cancer cells. Activation of these receptors has been associated with aggressive phenotypes and poor prognosis of breast cancer and other malignancies. Currently approved HER family targeted therapeutics are primarily directed against one member of the HER family.&#x2028; We have engineered a family of bispecific (HER1:HER3) heterodimers comprised of a human IgG1-Fc fragment fused with modified extracellular domains of HER1 and HER3. These compounds, termed Hermodulins, act as “ligand traps” and inhibit ligand-stimulated activity of all members of the HER family. In this study we have shown that Hermodulins can inhibit in vitro growth and motility in breast cancer cell lines, act synergistically with other HER-directed tyrosine kinase inhibitors and monoclonal antibody therapeutics in tumor cell antiproliferation assays, and decrease the formation of osteolytic bone metastases in animal models.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4127.
Radiofrequency ablation of breast cancer lumpectomy cavities – a technique intended to increase negative margins after breast conservation surgery. From benchtop to clinical use.
Authors: Rubio IT , Landolfi S , Kylstra JW , Klimberg VS , Coad JE 
Published: December 2010

Abstract
Abstract #4136
INTRODUCTION: Following breast conservation surgery, up to 49% of women require additional surgery due to close or positive lumpectomy margins. This results in significant additional burden for patient and society. This in vivo study assesses the feasibility of using intraoperative radiofrequency ablation (RFA) to treat the lumpectomy cavity walls and in situ extend the final negative margins, with consequent reduced need for re-excision surgery.&#x2028; METHODS: First, an in vitro study was performed to establish the performance characteristics of a RFA device in 12 mock lumpectomy cavities in fresh human breast or panniculus. These cavities were RFA-treated for 18 minutes with thermocouples recording. Second, an in vivo feasibility study was performed in 10 breast cancer pts (Italy) with clinically less than 2 cm tumors. The patients underwent lumpectomy, followed by in vivo 15 minute RFA cavity treatment, and subsequent quadrantectomy of the treated region. Third, an initial 5 pts (Spain) underwent lumpectomy and RFA only, with 4-5 punch biopsies obtained from the radial resection margin. The devitalized tissue radii around the cavity were measured using triphenyltetrazolium chloride (TTC) viability staining.&#x2028; RESULTS: In vitro temperatures in excess of 55C for 5 minutes were obtained 3mm from the radiofrequency probe and exceeded 45C at the treatment region edge. The in vitro and in vivo anterior/posterior treatment zone heights were 3.9 ± 0.5 cm and 4.4 ± 1.3 cm, respectively. The in vitro and in vivo distance between the anterior ablation zone edge and adjacent skin dermis measured 1.4 ± 1.1 cm and 0.9 ± 0.6 cm, respectively. The ablation zone edge focally extended to the dermal junction in one in vivo case. The three-dimensional devitalized tissue radii are presented in Table 1. In the 5 patients (Spain) where respective ablation radii were verified by punch biopsies, the devitalized tissue typically extended beyond the 7-14 mm radial depth of the biopsy sample. There were no postoperative complications with the use of RFA.&#x2028; &#x2028; CONCLUSIONS: This pilot data supports the feasibility of adjuvant radiofrequency lumpectomy cavity treatment to extend final negative tissue margins by approximately 1 cm. The extended margins have the potential to reduce the number of patients requiring re-excision surgery for close or focally positive margins. A multi-center trial aimed at validation of this technique has recently started.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4136.
Intra-operative specimen sonography: a valuable tool to identify tumor free margins during breast-conserving therapy.
Authors: Zarghooni V , Hübbel A , Moers C , Würstlein R , Mallmann P , Warm M 
Published: December 2010

Abstract
Abstract #4146
Background:&#x2028; Today, breast conserving therapy (BCT) represents the standard of care for the majority of patients with breast cancer. One significant technical difficulty remaining for the surgeon is the intraoperative estimation of tumor size in the attempt to achieve clear margins. We hypothesized that the use of intraoperative ultrasound evaluation of specimen would increase the rate of microscopically clear margins during lumpectomy.&#x2028; Methods:&#x2028; All patients who underwent lumpectomy for breast cancer at our hospital during 2007 were eligible. The study was non-randomized with retrospective data acquisition. In cases with positive ultrasound margins, the surgeon was guided to achieve disease- free margins. All cases with intraoperative specimen ultrasound were compared to cases without specimen sonography. We evaluated the technique of intraoperative sonography, the rate of tumor free margins, and the rate of re-excisions.&#x2028; Results:&#x2028; Of the 252 patients, 78 patients (31%) were evaluated with intraoperative specimen sonography. Operation times did not show significant differences in both groups.&#x2028; In the group with intraoperative specimen sonography the rate of microscopically free margins was 96%, compared to 81% in the control group. Intraoperative specimen sonography proved to be a useful adjunct in this series of patients because it significantly reduced the rate of re-excisions.&#x2028; Conclusion:&#x2028; Intraoperative specimen sonography proved to be a reliable and helpful tool for detection of tumor free margins in lumpectomy for breast cancer. It significantly reduces the rate of re-excions during breast conserving therapy.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4146.
The effect of zoledronic acid on aromatase inhibitor associated bone loss in postmenopausal women with early breast cancer receiving adjuvant letrozole: 36 months follow-up of ZO-FAST.
Authors: Eidtmann H , Bundred NJ , DeBoer R , Llombart A , Davidson N , Neven P , von Minckwitz G , Miller J , Schenk N , Coleman R 
Published: December 2010

Abstract
Abstract #44
Background: Aromatase inhibitors (AI) administered alone or sequentially following tamoxifen are the preferred treatments for hormone-receptor-positive (HRP) early breast cancer (EBC) in postmenopausal women (PMW). As a class effect, long term AI use is associated with an increased loss of bone loss. The primary analysis at 12 months of the Z-FAST and ZO-FAST studies demonstrated that the loss of bone mineral density (BMD) can effectively be prevented by zoledronic acid (ZA). Also, the ABCSG-12 study recently demonstrated a positive impact by ZA on disease recurrence in pre-menopausal women. This 36-months (mo) follow-up for ZO-FAST provides an insight into these issues and longer term safety data as pre-planned secondary endpoints.&#x2028; Materials and Methods: ZO-FAST has 1064 PMW with HRP EBC receiving Let (2.5 mg qd x 5 yrs). Pts with a BMD T-score &gt;-2 were randomized to immediate ZA arm (IMZA) vs delayed ZA arm (DZA). DZA pts receive ZA when either the post baseline T-score decreases to &lt; -2.0 or if a non-traumatic fracture occurs. All patients underwent a spine x-ray at baseline and at 36-mo to assess for asymptomatic fractures.&#x2028; Results: The updated primary endpoint continues to demonstrate the benefit of IMZA vs. DZA, with a treatment difference of 9.29(p&lt;0.0001) at the lumbar spine and 5.41(p&lt;0.0001) at the hip. 110 pts (20.5%) in the DZA have started ZA as per protocol at a median of 11.8 mo (range 0.03-38.3). The majority of these (82 pts) for T-score &lt; –2.0. There were 24(4.6%) pts who experienced clinical fractures in the IMZA and 26(4.9%) in DZA (Fisher's exact test:p value=0.88). A total of 676 pts (335 IMZA and 341 DZA) had both baseline and 36-mo spine x-ray reviewed centrally. The log rank test for disease recurrence (22 events-IMZA vs 37-DZA) has a p value of 0.0423. The log rank test for disease free survival (26 vs 43) has a p value of 0.0336. The median duration of Let is 43.3 vs 43.4 mo. Adverse events remain as previously reported, and are consistent with the known safety profile of the study drugs.&#x2028; Conclusion: The 36-month data continues to demonstrate the efficacy of ZA in preventing BMD loss. The trends in disease events are significant though preliminary at this 36 month analysis. Further follow up is needed to confirm these promising results. These benefits are observed in the context of a favorable safety profile. To date in this relatively small sample size, the rates of fracture are low and similar.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 44.
Chromosome 17 polysomy (Ch17) as a predictor of anthracycline response: emerging evidence from the UK NEAT adjuvant breast cancer trial.
Authors: Bartlett J , Munro A , Dunn J , Hiller L , Jordan S , Twelves C , Cameron D , Thomas J , Campbell F , Rea D , Provenzano E , Pharoah P , Caldas C , Earl H , Poole C 
Published: December 2010

Abstract
Abstract #45
Background: The role of HER2 and Topoisomerase IIα (TOPO2α) as predictors of anthracycline sensitivity remains controversial. To address this we conducted an analysis of HER2, Topoisomerase IIα amplification (TOPO2α-amp) and deletion (TOPO2α-del), chromosome 17 polysomy (C17) and Ki67 as prognostic and predictive markers in the UK National Epirubicin Adjuvant Trial (NEAT) which compared classical CMF with Epirubicin followed by CMF (NEJM 2006;355:1851-62).&#x2028; Methods: TMAs constructed with 1638/2021 tumors from patients in the NEAT study were analysed for HER2/TopoIIα gene alterations, C17 polysomy, and Ki67. Log-rank analyses explored the prognostic value of markers on relapse-free survival (RFS) and overall survival (OS). Cox-regression models tested independent prognostic value on RFS and OS in the presence of treatment, age, type of surgery, tumor size, nodal status, ER status and grade, and marker x treatment interactions for RFS and OS.&#x2028; Results: Of 1625 NEAT samples analysed, 806(50%) received anthracycline-containing treatment; 985(61%) were ≤50 years old; 1114(69%) had nodal involvement; 791 (49%) were ER+ve; 961(59%) had G3 tumours; and 893 (56%) had tumour size &gt;2cm. 19% were HER2-amp, 9% were TOPO2α-amp, 9% were TOPO2α-del, 18% were polysomic for C17 and 62% had high Ki67 (&gt;13.0%). HER2-amp and TOPO2α-del were significant poor prognostic factors (P&lt;0.001) for RFS and OS, and were independent variables in multivariate analyses. Other factors did not reach significance at the 1% level. No significant treatment interaction with anthracyclines was seen for HER2-amp (OS p=0.25, RFS p=0.51). Polysomy C17 was not prognostic but exhibited a significant treatment interaction with anthracyclines (RFS p=0.02, HRs 0.96 95%CI 0.73-1.26 vs 0.56 95%CI 0.33-0.97, OS p=0.06, HRs 0.97 95%CI 0.72-1.30 vs 0.60 95%CI 0.33-1.08). Patients with C17 polysomic tumours had significantly greater benefit from anthracyclines.&#x2028; Conclusions: Analysis of samples from the NEAT trial, which for the first time included HER2, TOPO2α, Ki67 and C17, strongly suggest that the most powerful predictor of benefit from adjuvant anthracyclines is chromosome 17 polysomy, perhaps as a marker of chromosomal instability, with a weak effect for HER2-amp. No effect was observed for differing TOPO2α status. Given the lack of consistency seen in previous studies with respect to HER2 and TOPO2α, we suggest that polysomy C17 could be the unifying predictive marker of anthracycline sensitivity, particularly as these data are confirmed by data from a separate meta-analysis of MA5 and BR9601 trials (SABCS2008).
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 45.
Association of estrogen receptor gene alpha polymorphisms with postmenopausal mammary density.
Authors: Ramos EH , Facina G , Silva ID , Costa AM , Nazario AC , Kemp C 
Published: December 2010

Abstract
Abstract #5003
Background: With the human genome studies, knowledge about polymorphisms started raising interest in a variety of fields and, in medicine, the evidence of direct action of polymorphisms on the arising and progression of diseases, disclosing the possibility of using them as disease predisposition markers. Substitutions, insertions or deletions which are transmitted through generations and reach frequencies equal or superior to 1% in the population are named polymorphisms. Knowing that the mammographic pattern is a multifactorial character, the objectives of this study were to evaluate a possible association of clinical characteristics and polymorphisms HaeIII, MspI and XbaI of the estrogen receptor gene alpha with postmenopausal mammary density. Materials and Methods: A prospective evaluation was made of 120 women who were not hormone therapy users and had no clinically or mammographically identified breast lesions. All of them underwent bilateral mammography, and the radiological density was determined by three independent observers, with two subjective evaluations based on the ACR-BIRADS® classification of mammographic patterns, 2003, and one computerized evaluation – the grey-scale histogram tool of the Adobe Photoshop® 7.0 software. Peripheral blood samples were obtained for DNA extraction, performed according to the GFX® Kit protocol from Amersham-Pharmacia. After DNA extraction, PCR-RFLP (Polymerase Chain Reaction - Restriction Fragment Length Polymorphism) was carried out for an analysis of the polymorphisms present in intron 1 (HaeIII and XbaI) and in exon 1 (MspI) of the estrogen receptor gene. Results: There was a high degree of concordance among the observers in the determination of mammary density (Kappa, Pearson and Spearman - p&lt;0.001). The associations of clinical characteristics with mammary density were: age (p=0.04), body mass index (p&lt;0.0001), age at menarche (p=0.02), age at menopause (p=0.120), age at first delivery (p=0.120), parity (p=0.09). The relation between the allele distribution of the polymorphisms and the density was: XbaI (p=0.02), HaeIII (p=0.65), and MspI (p=0.65). Conclusion: Polymorphism XbaI and the clinical factors age, menarche and body mass index showed to be associated with postmenopausal mammary density.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5003.
Fetal microchimerism in normal breast in healthy women and women with breast cancer.
Authors: Walline AD , Gadi V 
Published: December 2010

Abstract
Abstract #5048
Introduction: A lasting legacy of a fetus to his mother is a small number of stably persistent allogeneic cells, a phenomenon known as fetal microchimerism. We have been testing the hypothesis that fetal microchimerism is protective against cancer in the mother by participation in immune surveillance. Prior studies demonstrated that fetal microchimerism in the peripheral blood is associated with protection from breast cancer (Cancer Res, 67(19):9035-8 and PLoS ONE, 3(3):e1706). Here we examine whether the same association of fetal microchimerism extends to the tissue of interest, the breast.&#x2028; Methods: Total genomic DNA was extracted from frozen normal breast tissue adjacent to invasive disease in women with breast cancer. Control tissues were from reduction mammoplasty procedures performed for women with no prior history of invasive breast cancer. The presence of male DNA, presumably from a prior male fetus, was tested with a quantitative PCR assay for the Y chromosome gene, DYS14. Proportions of tissues harboring fetal microchimerism were compared between women with and without prior history of invasive breast cancer.&#x2028; Results: At present, tissues from 19 women with cancer and 19 without have been tested for the presence and quantity of fetal microchimerism using the DYS14 assay. Fetal microchimerism was detected less frequently in tissues from women with cancer (26%) than without (63%). The odds ratio for this protective association of fetal microchimerism with breast cancer is 0.21 (0.04-1.0 95% confidence interval; p=0.05). A trend towards larger median quantities of fetal microchimerism was noted in control tissues versus normal breast from cancer patients (0.34 versus 0 fetal genomes/million maternal cells, p&gt;0.05).&#x2028; Conclusions: Preliminary results suggest that the negative association of breast cancer and fetal microchimerism observed previously in the blood is also reflected at the level of the tissue of interest. These results merit further investigation in the breast tissue of controls to identify the phenotype of the cells detected. Furthermore, the findings here provide further support to the overall hypothesis that fetal microchimerism may participate in immune surveillance against breast cancer in healthy women.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5048.
Infiltration of intratumoral T cells and regulatory T cells are associated with p53 expression and ER status in early breast cancer: a Korean breast cancer study.
Authors: Park K , Kim A , Woo O , Ryu W , Yoon S , Suh H , Choi I , Suh J , Kim Y , Kim J , Koo B 
Published: December 2010

Abstract
Abstract #5049
Background: Immune responses, such as rich lymphocyte infiltrate, have shown associated with improved clinical outcomes in patients with breast cancer. Recently, number of tumor-infiltrating regulatory T cell has been identified as a poor prognostic marker. There is, however, not enough data evaluating the associations between the clinicopathologic factors and quantity or quality of TILs in Asian breast cancer patients.&#x2028; Material and methods: CD4-, CD8-, and Foxp3-positive tumor-infiltrating lymphocytes (TILs) were detected by immunohistochemistry using the paraffin-embedded samples from the 40 patients with early stage (I-III) breast cancer. Expression status of ER, PR, HER-2, p53, and Ki-67 were also evaluated by immunohistochemistry. Clinical data, such as pathologic stage, patient's age, were available for statistical analysis.&#x2028; Results: Statistically significant correlation between ER expression and CD8/CD4 ratio of the TILs (Spearman r=0.447, p=0.024) was observed. Other clinicopathlogical factors, such as PR, tumor size, nodal metastasis, tumor grade, did not show significant correlation with ratio of the TILs. Additionally, tumors with more dense accumulation of p53 protein were associated with recruitment of higher number of Foxp3-positive regulatory T cells (Spearman r=0.52, p=0.0002). Ki-67, a proliferation index of the tumor cells, was also statistically significantly associated with infiltration of regulatory T cells (Spearman r=0.46, p=0.019).&#x2028; Discussion: Our data showed that ER-positive tumors had higher ratio of CD8/CD4 TILs, which is opposite result from the previous studies. In addition, p53 overexpression and high proliferation index of the breast cancer were associated with high regulatory T cell infiltration, but not with total TIL. The role of the p53 overexpression of the tumor cells in determining immune balance and its prognostic implication will be evaluated in the future study.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5049.