bluuebunny/crossref_metadata_2025_split huggingface dataset:
A multistage nanodelivery system for therapeutic applications and medical imaging: in vivo biodistribution and efficacy study in a murine orthotopic breast cancer model.
Authors: Tasciotti E , Bhavane R , Godin-Vilentchouk B , Serda R , Liu X , Robertson F , Ferrari M 
Published: December 2010

Abstract
Abstract #2160
The ability to deliver therapeutic compounds specifically to diseased sites is crucial for effectively treating human illnesses. Nanotechnology is emerging as a tool for resolving challenges in the delivery of poorly administrable drugs by transforming them into nanometer-sized particles (nanotherapeutics). The progress thus far gave rise to a large number of nanotherapeutics, but the accomplishment of the original objective, which is to increase drug concentration at target sites, has not been fully realized. A series of biological barriers pose as insurmountable obstacles which limit or completely abolish the ability to selectively deliver a therapeutic agent. We hypothesized that a multi-stage system for systemic delivery (MSDS) could be designed to interact with and successfully overcome sequential biological barriers. We developed a MSDS using biodegradable, biocompatible silicon particles optimally sized and shaped to travel into the blood flow, avoid RES, marginate and adhere to tumor vasculature. The first stage carriers (FSCs) contain nanopores of specific size that can load, carry, release over time, and deliver multiple types of second stage nanoparticles (SSNs). The nanoparticles can be optimized to reach, through vessels fenestrations, the tumor environment and finally release their therapeutic payload into target cells.&#x2028; &#x2028; The ease in chemically modifying the silicon surface permits the attachment of fluorescent and radiolabeled imaging molecules to the FSCs. Fluorescent and magnetic SSNs can be loaded into the pores of the FSCs. Once assembled, the resulting MSDS can be imaged using different in vivo imaging modalities from its administration to its final localization into the body. We further modified our FSCs with PEG molecules to increase their circulation time and with antibodies directed against the VEGFR2 membrane protein to increase the localization of the MSDS in tumor associated vessels. We monitored the biodistribution of all MSDSs and characterized their biocompatibility in the different tissues. Finally, we loaded the pores of the FSCs with a lipidic nanoformulation of the potent anti cancer drug doxorubicin (dox-liposomes and dox-micelles) and followed the efficacy of this treatment. Taken together, these studies provide first time evidence that silicon nanoporous particles can be used as effective carriers for the simultaneous delivery of different nanotherapeutics in vivo.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2160.
Can nipple-areola-sparing mastectomy be an alternative to mastectomy? Over 10 years of follow up at a Japanese institution.
Authors: Sakurai T , Umemura T , Jinta E , Shimizu S , Suzuma T , Yoshimura G , Sakurai T 
Published: December 2010

Abstract
Abstract #22
Introduction: Cosmetic outcome is one of the most important aspects of surgical treatment of breast cancer. Therefore, to maximize the cosmetic outcome for patients who require a mastectomy, what can be done from an oncologically safe perspective must be considered. Recent reports have suggested that nipple-areola-sparing mastectomy (NSM) is oncologically as safe as a classical mastectomy (MT) and provides a better cosmetic outcome than MT. However, little is known about the long-term outcome of NSM.&#x2028; Aim: To determine the oncological and technical outcomes of NSM compared with MT using long term follow-up data.&#x2028; Patients and Methods: We retrospectively analyzed 788 patients, median age 51 years, with primary breast cancer who underwent NSM from 1985 to 2004. The indication of NSM in this study was defined as being for any stage, any tumor size and any tumor-areola distance. Briefly, NAC was preserved when palpation and the outlook of the nipple was normal. Median tumor size and tumor-areola distance were 2.5cm (0-10.0) and 1.8cm (0-9.0), respectively. Our surgical notes for NSM were; (1) a thin flap (approximately 5 mm thick subcutaneous adipose tissue) was placed close to the tumor, and a thick flap (more than 1cm thick subcutaneous adipose tissue) was created more than 2cm away from the tumor to conserve breast volume using subcutaneous fat, and (2) tissue under the NAC was left at 5 mm in thickness, but the major ducts were removed from within its lumen. Eighty-one patients (10%) underwent immediate breast reconstruction (IBR) using implants. We also analyzed 144 patients with breast cancer who underwent MT in the same period as those who underwent NSM. No patient received radiotherapy. We compared the local recurrence rate (LRR), disease-free survival (DFS) and overall survival (OS) between 788 NSM and 144 MT cases.&#x2028; Results: Median follow-up of NSM and MT was 92 (10-252) and 87 (0-231) months, respectively. To our surprise, no complications of NSM including nipple and areola necrosis were recorded (0/788). For NSM, there were 70 patients (8.9%) with local recurrence, including 23 (2.9%) at the nipple, 4 (0.5%) at the areola, 4 (0.5%) at both nipple and areola, and 39 at the skin flap (4.9%). This suggested that the rate of NAC relapse was quite low. There were no significant differences in LLR between NSM and MT, (10y, 8.9% vs. 7.6%, p=0.62), DFS (10y, 83% vs. 83%, p=0.34) and OS (10y, 88% vs. 86%, p=0.34), respectively. Cosmetic outcome of NSM was better than that of MT in the majority of patients.&#x2028; Conclusion: These results suggested that NSM provides a good cosmetic outcome and is as safe oncologically as MT. Our long term follow-up data shows that NSM is a possible alternative to mastectomy.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 22.
GRB7-dependent pathways are potential therapeutic targets in triple-negative breast cancer.
Authors: Sparano JA , Gray R , Goldstein LJ , Childs BH , Bugarini R , Rowley S , Baker J , Shak S , Badve S , Baehner FL , Perez EA , Shulman LN , Martino S , Sledge Jr. GW , Davidson NE 
Published: December 2010

Abstract
Abstract #25
Background: Breast cancer lacking expression of the estrogen and progesterone receptor and overexpression of HER2/neu (ie, "triple-negative” disease) accounts for about 10-15% of all breast cancer and is characterized by a higher risk of recurrence, early recurrence, resistance to cytotoxic therapy, and lack of any specific targeted therapy.&#x2028; Methods: We extracted RNA from primary tumor samples of 246 patients with stage I-III triple-negative breast cancer (confirmed in a central lab) treated with 4 cycles of adjuvant doxorubicin (60 mg/m2) plus cyclophosphamide (600 mg/m2) or docetaxel (60 mg/m2) who were enrolled on trial E2197, and correlated RNA expression (by quantitative RT-PCR using a panel of 371 rationally selected genes) with recurrence. There was no difference in recurrence between the two treatment arms in the entire study population, nor in the 246 patients in this analysis (of whom 59 recurred) after a median followup of 76 months.&#x2028; Results: Higher expression of GRB7 was the only gene significantly associated with an increased risk of recurrence (nominal p value 0.0000853, Korn's adjusted p value controlling false discovery at 10% (KP10) p=0.0359), but did not correlate with any clinicopathologic features except age (low expression associated with age &gt; 65 years, p=0.03). In a Cox proportional hazards model adjusted for age, nodal status, tumor size, and grade, higher GRB7 expression was associated with an increased risk of recurrence when evaluated as a continuous variable (hazard ratio 3.41; p = 0.001) or as a dichotomous variable (hazard ratio 2.24 above vs. below median; p=0.006). The 5-year recurrence rates were 10.5% (95% C.I.7.8%, 14.1%) in the low and 20.4% (95% C.I. 16.5%, 25.0%) in the high GRB7 groups. There were only six genes whose expression correlated with GRB7 (r&gt; 0.4), including ERBB2 (r=0.70), DDR1 (discoidin domain receptor tyrosine kinase 1; r=0.53), KRT19 (keratin 19; r=0.49), ERBB3 (r=0.48), GPR56 (G protein-coupled receptor 56; r=0.48) and PHB (prohibitin; r=0.42).&#x2028; Conclusions: GRB7 is a calmodulin-binding protein which has an SH2 (Src homology 2) domain that binds to phosphorylated tyrosine residues and other specific protein targets, and which plays a critical role in signaling (EGFR, HER2), motility (eprhins), migration (focal adhesion kinase), and cell-matrix/cell-cell interactions (integrins). Higher GRB7 RNA expression is associated with a significantly higher risk of recurrence in triple-negative breast cancer, indicating that GRB7 or GRB7-dependent pathways are potential therapeutic targets in triple-negative disease.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 25.
Atypical and columnar cell lesions in breast needle biopsies for indeterminate microcalcifications: predictors of higher risk findings requiring surgical excision.
Authors: Albarracin CT , Sigauke E , Whitman G , Yang WT , Resetkova E , Johnson MM , Nguyen CV , Sneige N 
Published: December 2010

Abstract
Abstract #3004
Background: Columnar cell lesions (CCL) are frequently identified in biopsies performed for calcifications. The primary objective of this study is to identify histologic features of CCL in directional vacuum-assisted needle biopsies (DVAB) that could predict a higher risk lesion requiring excision.&#x2028; Design: From June 2002 to January 2008, we retrieved the materials for 88 DVABs and their subsequent segmental resections. We excluded carcinomas, intraductal papillomas, fibroadenomas, adenosis, or radial scars. Using World Health Organization criteria, CCLs were classified as CCL with no atypia (CCL-NA), CCL with cytologic atypia (CCL-CA; flat epithelial atypia), or architectural atypia/atypical ductal hyperplasia (CCL-ADH) in the background of CCL. In cases with atypia, the involved terminal duct lobular units/ducts (TDLUs) were quantified. Atypical cases were separated two groups as follows: minimal ADH (≤2 TDLU and minimal cytologic atypia) and extensive ADH/borderline DCIS (≥3 TDLU and/or significant cytologic atypia bordering on DCIS).Radiographs were evaluated to assess amount of calcifications removed. Biopsy results were correlated with the subsequent surgical excision results.&#x2028; Results: Eight of 88 biopsies were excluded because of overdiagnosis or because the lesions were not associated with microcalcifications. The remaining 80 biopsies included 5 cases of CCL-NA, 4 pure CCL-CA, 20 mixed CCL-CA + ADH and 51 pure CCL-ADH. Microcalcifications were identified in association with the targeted lesions. There were no higher risk findings in any of the resection specimens with CCL-NA and pure CCL-CA. Ten of the atypical lesions showed carcinoma on excision (9 DCIS and 1 invasive cancer). Twenty-five percent (9/36) extensive ADH/borderline DCIS showed carcinoma on excision. In contrast, only 2.5% (1/39) of minimal ADH cases showed carcinoma on excision. Radiologic review revealed residual abnormality in this one case.&#x2028; Conclusion: In summary, the extent of lobular involvement by atypia (CCL-CA or CCL-ADH) correlated with the presence or absence of higher risk lesions upon subsequent excision. These results suggest that additional surgery may not be necessary for CCL-CA or CCL-ADH that is limited to ≤ 2 foci provided sampling of the microcalcifications is adequate.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3004.
MUC1 expression in early-stage triple-negative breast cancer.
Authors: Miedler J , Abdul-Karim F , Wang N , Baar J 
Published: December 2010

Abstract
Abstract #3009
Background. Triple-negative breast cancer (TNBC) comprises ∼10-15% of newly-diagnosed early-stage breast cancer. Most TN tumors are high grade and have a high incidence of recurrence and distant metastases. Patients with early stage TNBC usually do not receive any maintenance systemic therapy beyond standard cytotoxic chemotherapy and may therefore benefit from novel experimental therapies, including immunotherapy. MUC1 is a tumor antigen expressed on differentiated tumor cells, including BC, and therefore represents an ideal target for MUC1-based vaccination. In this study, we evaluated TNBC for the expression of MUC1 by immunohistochemical (IHC) analysis.&#x2028; Material and Methods. Fifty-three cases of ER(-) PR(-) HER-2/neu(-) early-stage BC were evaluated for expression of the MUC1 glycoprotein by IHC stain analysis. Immunoreactivity was graded based on the intensity and percent of tumor cells staining for MUC1. Intensity of staining was graded as negative (0), positive (1) or strongly-positive (2), and the percent of tumor cells staining positively was graded from 0 to 100%. A specimen was considered positive if immunoreactive cells were found in at least 5% of tumor cells. An overall score of 0 to 2.0 was then calculated for each case by multiplying the intensity of staining by the percent of tumor cells staining positively.&#x2028; Results. Forty nine of the fifty three cases of TNBC (92%) were MUC1+ by IHC stain analysis. The mean score was 0.90, with a range of 0 to 1.9. Cases were evenly distributed over this range, and the majority of cases (66%) exhibited moderate to strong expression of MUC1 (score 0.5 to 1.90). A minority of cases (26%) demonstrated weak expression, and 8% of cases lacked expression of MUC1 by study criteria.&#x2028; Discussion. MUC1 expression has been documented in the epithelium of secretory tubules, acini, and intralobular ducts of normal breast tissue and in breast carcinoma of undefined subtype. However, this is the first study to specifically evaluate TNBC for the expression of MUC1. The results of our study suggest that the vast majority of cases of early stage TNBC express MUC1. Since other MUC1+ tumors such as prostate, pancreatic and ER+ breast cancer have been successfully vaccinated with MUC1-based peptide vaccines, this study suggests that consideration may be given to patients with early stage TNBC as possible candidates for such novel MUC1-based vaccines after having completed standard therapies for TNBC.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3009.
Intra operative determination of axillary node metastasis by RT PCR: experience on 50 breast cancer patients.
Authors: Baranzelli M , Chauvet M , Verhults P , Giard S , Révillion F , Peyrat J , Robin Y , Bonneterre J 
Published: December 2010

Abstract
Abstract #3012
Background: Sentinel lymph node (SLN) status is highly predictive of overall axillary lymph node involvement. SLN positive patients(pts)with macro or micrometastasis require delayed axillary clearance. Intraoperative imprints have a good sensitivity for detection of macrometastasis but micrometastases are seldom diagnosed. Thus, we tested the intraoperative determination of axillary node metastasis according to the Rapid Gene Search Breast Lymph Node (BLN) Assay (Veridex) based on RT-PCR.&#x2028; Patients and methods:50 pts operated between September 17 and March 20 ,2008, had a SLN procedure. Lymph nodes were cut in 2 mm slices, and 1 out of 2 was examined with Rapid BLN Assay; the other one had intraoperative imprints and definitive histological assessement in paraffin-embedded sections including serial slices with hematoxilin eosine safran coloration and Cytokeratine AE1-AE3 immunochemistry.&#x2028; Results : 103 lymph nodes were examined with a median number of 2 SLN by pt. With Rapid BLN Assay, 12(9 pts) were positive and confirmed by histological interpretation on the other half for 11 (8 pts). 89 lymph nodes were negative (41 pts); in 1 (1 pt), isolated tumor cells (CTI) were detected in the other half at histological interpretation. Intraoperative imprints detected 4 macrometastases. One node declared positive at the intra-operative examination imprint corresponded to a granulomatous lesion after histological interpretation and Rapid BLN Assay was negative. Sensitivity was 31% for intraoperative imprints, 92% for Rapid BLN Assay and the histological examination of paraffin--embedded sections. The median time for intraoperative determination was 34 minutes for 1 SLN compared with 20 minutes for imprints.&#x2028; Conclusion: Given the high sensitivity of the rapid BLN assay, the excess duration of the procedure is acceptable for the surgeon. Furthermore, this procedure avoids a secondary axillary clearance in pts without intraoperative examination or with negative imprints and with metastases in SLN.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3012.
Quality improvement analysis of HER2 FISH testing in breast cancer in response to the new ASCO/CAP guidelines.
Authors: Fang M , Thalody V , Tannenbaum S 
Published: December 2010

Abstract
Abstract #3013
Background: The new ASCO/CAP guidelines for HER2 testing in breast cancer redefined the interpretation of HER2 FISH testing result. A new category of equivocal result is defined as FISH ratio of 1.8-2.2. Patients with equivocal results constitute a poorly studied subgroup with uncertain association of test scores to benefit from HER2-directed therapy. Additional quality control and quality assurance recommendations were also detailed in the guideline. As part of our institutional effort for quality improvement of HER2 testing, we reviewed the FISH HER2 testing performed in our institution for the past four years.&#x2028; Methods: The FDA-approved PathVision HER2 FISH kit (Abbott Molecular, CA) was used for all FISH testing. The Herceptest ParmDx antibody (Dako Cytomation) and the Neu-Her2/Cerb-2 antibody (Vision Biosystems) were used for all IHC testing. The new ASCO/CAP interpretation criteria were applied to the FISH enumeration results and compared with the IHC results and interpretation. Correlation with clinical decision of trastuzumab therapy and clinical outcome was reviewed.&#x2028; Results: A total of 554 samples between 2004 and 2008 were tested for HER2 FISH. According to the new interpretation criteria, 12.8% of the samples had amplified values and 3.8% of the samples had equivocal values. IHC was negative for Her2 for all the samples with equivocal FISH results. Only one patient was treated with trastuzumab. In addition to this equivocal category, some samples showed genetic heterogeneity with some of the tumor showing cells with HER2 amplification whereas cells at different areas of the same tumor were not amplified. Half of these patients were treated and the remaining 50% were not. The discordant rate between FISH and IHC was 3.6% overall, and aneusomy 17 may explain some of the discordance. Of patients with discordant HER2 results by FISH and IHC, physicians' decision to treat with trastuzumab or not appeared to be based on either FISH or IHC with equal frequencies.&#x2028; Conclusion: Due to small sample size and retrospective nature of this review, outcome data was uninformative in these small cohorts. As suggested by the ASCO/CAP expert panel, pooling data from all adjuvant trastuzumab trails on subjects with equivocal results would be helpful to provide an evidence base for physicians to make treatment decisions. Alternatively, we are beginning to explore molecular expression profiles to see whether some of these equivocal or discordant cases behave more like HER2 positive or negative patients.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3013.
Effects of short-time tamoxifen therapy on breast cancer apoptosis and cell cycle regulators.
Authors: Madeira M , Millen EC , Vivian F , Logullo [F , Gebrim LH 
Published: December 2010

Abstract
Abstract #3017
Background: Tamoxifen is the most used endocrine therapy in patients with estrogen and/or progesterone positive receptors breast cancer. Tamoxifen acts in a complex manner as estrogen antagonists in tumor tissue, and its interaction with growth factors may lead to inhibition of cell proliferation.&#x2028; Objectives: The aim of this study was to evaluate the expression of estrogen receptor (ER), progesterone receptor (PR), COX-2, Ciclyn D-1, Bcl-2, BAK, BAX and nitric oxide synthase (NOS I, II and III) in breast carcinoma cells using immunohistochemical essay on tumor samples before and after short-time (14 days) exposure to tamoxifen.&#x2028; Material and Methods: A randomized double-blind study was performed with 29 stage II and III breast cancer patients divided according to the following groups: Group C (n= 15 / control) and Group T (n=14 / 20mg of TAM/day for 14 days). Immunohistochemical expression of ER, PR, COX-2, Ciclyn D-1, Bcl-2, BAK, BAX and NOS I, II and III were evaluated before (diagnosis biopsy) and after treatment. The results were classified according Allred score (semi quantitative), based on the intensity and fraction marked cells. The scores of each reaction were compared pre and post treatment, and also to the control group.&#x2028; Results: The mean scores of each reaction before and after treatment for Group T and Group C are seen in the table 1.&#x2028; &#x2028; No significant difference was observed with short-time tamoxifen therapy (table 2 - Mann Whitney test).&#x2028; &#x2028; Discussion: Although tamoxifen has been in clinical use for over 30 years in oncology, its complex manner of action is not totally elucidated. Our results did not show a significant change in breast cancer apoptosis and cell cycle regulators, but bring new data about the short-time exposure to tamoxifen.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3017.