bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic significance of sentinel nodes metastases in breast cancer patients without axillary node dissection or axillary radiotherapy: CBCSG-001 trial.
Authors: Wang Y , Wang C , Fan L , Mu D , Gao Y , Li J , Zhong W 
Published: December 2010

Abstract
Abstract #1015
Background: China multicenter study of sentinel lymph node biopsy (SLNB) substituting axillary lymph node dissection (ALND) in breast cancer– CBCSG-001 trial was conducted from Jan. 2002 to Jun. 2007, with 1,970 SLNB pts recruitment. One of the second objectives of the CBCSG–001 trial was to evaluate the optimal methods and intervals for the detection of SLN macrometastases, MMs and isolated tumor cells (ITCs) and their prognostic significance in patients received SLNB without ALND or axillary radiotherapy.&#x2028; Material and Methods: Two hundred and forty-five continuous breast cancer patients with 569 SLNs identified “negative” with routine standard HE stain carried on initial 4 levels were retrospectively analyzed. All the patients received SLNB only, without ALND or axillary radiotherapy after the diagnoses of metastases in their SLNs later. All SLNs were step sectioned (SS) at 100µm interval, and for each level both HE and IHC with AE1/AE3 were performed. Forty-nine patients were identified to have metastases, with macrometastases of 12.2%, micrometastases of 61.2%, and isolated tumor cells of 26.5%. All patients had received SLNB only, with no ALND and axillary radiotherapy.&#x2028; Results: Of the 245 patients, breast conserved surgery and SLNB were performed on 106 patients (43.3%), and mastectomy and SLNB in 139 patients. With a median follow up of 50 months, there were 20 breast related events occurred. The disease free survival (DFS) of patients with routine negative SLNs was 91.6%, and 93.9% for patients with positive SLNs after SS with HE+IHC (p&gt;0.05). The overall survival (OS) were 97.4% and 98.0 for each group, respectively (p&gt;0.05). The results were the same for patients with macrometastases, micrometastases, and isolated tumor cells. Due to the relatively less events occurred, the DFS and OS had not been calculated for macrometastases, micrometastases, and isolated tumor cells, separately.&#x2028; Discussion and Conclusions: Without ALND and axillary radiotherapy, there were no significant differences of DFS and OS between patients with routine negative SLNs and patients with positive SLNs after SS with HE+IHC. It might be safe for these patients to receive SLNB only. The possible reasons might include: SLNs were the only positive lymph nodes in more than 60% patients, effective adjuvant systemic therapy for regional lymph nodes just as neoadjuvant chemotherapy, axillary coverage of radiotherapy in patients with breast conserved therapy, and the relatively less events occurred during the 50 months follow up period.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1015.
Intraoperative training on the techniques of sentinel node biopsy in breast cancer.
Authors: Delaloye JF , Pampallona S , Cuchard P , Monod JF , Brunisholz Y 
Published: December 2010

Abstract
Abstract #1016
Background: Sentinel node biopsy (SNB) is an accurate procedure for axillary staging and the surgeons' experience is crucial for its proper application. A training session involving 20-30 cases is widely practiced. In order to speed up this learning curve, surgeons were trained intraoperatively by one instructor. The purpose of this report was to evaluate the procedure by comparing the results of the instructor with those of the trainees.&#x2028; Material and Methods: Patients with invasive breast cancer (T0-T2[&lt;3cm]N0M0) were considered eligible. Lymphatic mapping was obtained by peritumoral or periareolar injections of technetium with or without blue dye. Complementary axillary lymph node (LN) dissection was performed when SNB was unsuccessful or when SN were positive. Patients were distributed in 4 groups : (i) teacher's learning curve (SNB followed by complementary axillary dissection) (n=40), (ii) SNB by instructor (n=130), (iii) SNB by trainees with supervision from instructor (n=63), and (iv) SNB by trainees alone (n=303). The criteria of patients' selection, the parameters of success of the SNB procedure, and the LN metastases were compared. Reported p-values compare groups (ii) to (iv).&#x2028; Results : From May 1999 to December 2007, 808 patients underwent a SNB. The SN identification rate was 98% in the group (i), 98% in the group (ii), 97% in the group (iii), and 99% in the group (iv) (p=0.196). SN were positive in respectively 28%, 31%, 28%, and 29% of patients. Overall positive nodes (SN and LN) were diagnosed in respectively 28%, 31%, 30%, and 30% of patients (p=0.833). The distribution of isolated tumor cells, micrometastases, and metastases was not statistically different between the four groups (p=0.163).&#x2028; Conclusion: These comparable results confirm the success with which the SNB was taught. This strategy avoided the 20-30 SNB with complementary axillary dissection.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1016.
A new hand-held gamma camera for sentinel node detection in breast cancer. The Minicam experience in 50 cases.
Authors: Garbay J , Ricard M , Lumbroso J , Rimareix F , Uzan C , Gouy S , Leroy P 
Published: December 2010

Abstract
Abstract #1021
Background: The Minicam* is a high-resolution 1.6 inches field-of-view hand-held gamma camera. We used it to detect breast cancer sentinel nodes (SN).&#x2028; Material and Methods : This is a prospective, non-randomized, blind study comparing the minicam (MC) and classic scintigraphy (CS) in 50 cases. All patients underwent CS, and the surgeon used the MC in the operating room blinded to the CS results. Then CS images were visualized and the operation was performed as usual with a probe. At the end of the procedure, control MC images were obtained and displayed.&#x2028; Results : Isotopic detection failed in a single case (1/50). Concordance between the MC and CS was very good in 33 cases (67.5%). In 6 cases (12%), the MC was better and in 10 cases (20.5%) CS was better, in terms of the number of detected nodes. The post-procedure control images were always negative. The surgeon found that the MC was better than the probe for node localization in 2 difficult cases. It took 4 to 10 minutes using the MC in the first 8 cases, and a mean of 2 minutes (range 1-3 min) thereafter. The small screen size (1.6x1.6 inches) was noted as the cause of difficulties in 12 cases and was associated with 4/10 failures.&#x2028; Discussion : This minicam device is easy to use for the surgeon, with a user-friendly software, a short learning curve and good accuracy. The small screen size is really the only drawback. On the basis of this first blind comparison with CS, a larger multicentric study will be initiated.&#x2028; * Euromedical, France.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1021.
Correlation between pN0(mol+) and standard clinico-pathological prognostic factors in SLN of breast cancer patients.
Authors: Varela M , Moreno A , Falo C , Villalba E , Benito E , Serra J , Fernández A , Escobedo AP 
Published: December 2010

Abstract
Abstract #1025
Objective: To establish the significance of disease detected by reverse transcription polymerase reaction (RT-PCR) in sentinel lymph nodes (SLN) of breast cancer patients.&#x2028; Background: In breast cancer patients, the axillary status is the most important prognostic factor. The RT-PCR appeared to be a sensitive method, but the relevance of pN0(mol+) has not yet been established.&#x2028; Methods: 674 patients with T1-T3 primary invasive breast cancer were included in a prospective study. SLN were analysed by routine pathology analysis (staging with hematoxylin-eosin – H&E– and immunohistochemistry – IHQ–) and RT-PCR. Correlations between molecular diagnostics and standard clinicopathological prognostic factors, including St. Gallen risk categories were analyzed.&#x2028; Results:&#x2028; Of the 674 patients, 131 (19.4%) had one or more pathology-positive SLN detected by routine pathological, 137 (20.3%) were exclusive molecular positive - pN0 (mol+) - and 406 (60.2%) were without evidence of disease.&#x2028; We evaluated correlation between nodal staging with pathological and molecular analysis and clinicopathological factors in the whole patient cohort. Positive cases were significantly associated with tumor size (p&lt;0.010), histological grade (I-II vs. III) (p&lt;0.048), vascular invasion (p&lt;0.000) and St. Gallen risk category (p&lt;0.003).&#x2028; Conclusions: molecular staging of SLN using RT-PCR could serve as a useful complement to standard clinico-pathological risk factors. Correlation between pN0(mol+) patient group with survival rates will define the clinical relevance of lymph node molecular detected micrometastases in this patient population.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1025.
Efficacy of bevacizumab (BV) plus docetaxel (D) does not correlate with hypertension (HTN) or G-CSF use in patients (pts) with locally recurrent (LR) or metastatic breast cancer (mBC) in the AVADO phase III study.
Authors: Chan A , Vanlemmens L , Conte PF , Beith J , Samonigg H , Verma S , Srimuninnimit V , Martoni A , Miles DW 
Published: December 2010

Abstract
Abstract #1027
Background: BV (Avastin®), a monoclonal antibody to VEGF, significantly improved PFS and response rate in pts with LR or mBC when combined with 1st-line taxane CTx in two randomised phase III studies: E2100 (BV + weekly paclitaxel) and double-blind, PL-controlled study AVADO (two different BV doses + D). Efficacy of some biological agents correlates with certain toxicities. This was hypothesised for HTN with BV use and investigated in the AVADO study in an exploratory analysis. In contrast, CSF use in pts receiving CTx may adversely affect response, so correlation of G-CSF use with efficacy was also examined.&#x2028; Methods: This study compared BV 7.5 or 15mg/kg + D 100mg/m2 with PL + D in 736 pts with inoperable LR or mBC with no CTx 6 months prior to randomisation (12 months if taxane-based), ECOG PS 0–1 and adequate LVEF. D was administered q3w for up to 9 cycles, BV/PL q3w until disease progression or unacceptable toxicity.&#x2028; Results: The safety population consisted of 730 pts. Reported grade 3–4 HTN was low in the AVADO BV arms (1 pt, 0.4% [BV 7.5mg/kg]; 8 pts, 3.2% [BV 15mg/kg]), therefore the analysis of correlation with efficacy was performed for all grades of HTN. Data for HTN of all grades and G-CSF use in all randomised pts are shown below. Use of G-CSF did not affect dose intensity of D.&#x2028; &#x2028; Conclusions: Efficacy of BV + D in pts with LR or mBC did not appear to correlate with incidence of all grade HTN or G-CSF use. The apparent PFS and response benefit in the BV 7.5mg/kg arm for pts with HTN should be taken with caution as it is based on a small number of pts and may be due to an imbalance in baseline characteristics or a higher likelihood of detecting HTN in patients receiving study therapy for longer. Analysis of a larger dataset is needed to provide further data in this context.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1027.
VEGF, VEGFR2 and HIF-1α expression in circulating tumor cells (CTCs) of breast cancer patients.
Authors: Kallergi G , Agelaki S , Gannoukaraki V , Markomanolaki H , Lianidou E , Mavroudis D , Georgoulias V 
Published: December 2010

Abstract
Abstract #1028
Background: Development of metastasis is associated with the presence of circulating (CTCs) and disseminated (DTCs) tumor cells in peripheral blood and bone marrow of breast cancer patients, respectively. Hypoxia and Vascular Endothelial Growth Factor (VEGF) play an important role in angiogenesis. There is no data published concerning the expression of HIF-1α and VEGF/VEGFR in CTCs. Methods: Double staining immunofluoresent experiments were designed to test the expression of VEGF, VEGFR and HIF-1α in CK (Cytokeratin)-positive CTCs from 34 metastatic breast cancer patients. PBMC cytospins were double stained with a monoclonal pancytokeratin antibody (A45-B/B3) along with each of the following: VEGF, VEGFR2 or HIF-1α polyclonal antibodies, respectively. Results: According to our experiments, CTCs from 62%, 47% and 76% of patients expressed VEGF, VEGFR2 and HIF-1α, respectively. In addition, VEGF, VEGFR2 and HIF-1α were expressed in 73%, 71% and 56% of the total number of examined CTCs, respectively. In 24% of the patients CTCs expressed all the investigated molecules. VEGF expression in CTCs was confirmed by performing RT-PCR with VEGF-specific primers in immunomagnetically-separated epithelial cells. Double and triple staining experiments and confocal microscopic analysis of immunomagnetically-isolated CTCs confirmed that VEGF was co-expressed with HIF-1α and VEGFR. Discussion: VEGF and VEGFR2 colocalization in CTCs indicate the presence of an autocrine loop in these cells. Our results demonstrate VEGF, VEGFR2 and HIF-1α expression in CTCs of patients with metastatic breast cancer and thus constitute the basis for using anti-angiogenic therapy for their elimination.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1028.
Populations of cells exhibiting epithelial-mesenchymal transition (EMT) or stem cell characteristics can be propagated from a single inflammatory breast cancer (IBC) cell line based on culture conditions.
Authors: Debeb BG , Hall CS , Xu W , Ueno NT , Reuben JM , Robertson F , Lucci A , Buchholz TA , Hortobagyi GN , Cristofanilli M , Woodward WA 
Published: December 2010

Abstract
Abstract #103
We have previously reported the isolation of a novel IBC cell line (MDA-IBC-1) from human pleural effusion fluid by passaging cells under 3-dimensional (3D) mammosphere (progenitor-promoting) conditions and isolating attached 2-dimensional (2D) cells from ultralow attachment plates. Mammosphere culture is serum-free and growth factor enriched. Serum-starving 2D cells leads to spontaneous formation of floating mammospheres with the same percentage of CD44+24- cells as 3D cultured mammospheres. 2D cells display distinct fibroblastic morphology. Here we report that passage in 2D (standard) or 3D (mammosphere) culture selects for different molecular phenotypes: EMT in 2D and stem/progenitor-like in 3D. 3D cells are generated from 2D cells for all experiments and are examined at second passage. RT-PCR reveals embryonic stem cell pluripotency factors Oct-4, Nanog, Sox-2 and Rex-1 are expressed in 3D but not 2D MDA-IBC-1 cells. MicroRNAs reported to be involved in self-renewal of breast cancer cells including Let-7a,b,c,d,e and f are decreased in 3D cultures (&gt;5 fold decrease) compared to 2D. MiR16, 21, 125b and 200c are also markedly reduced in 3D vs. 2D cells. On the other hand, EMT proteins, N-cadherin, vimentin, and fibronectin are only expressed in 2D culture and higher expression of snail and slug is observed in 2D compared to 3D. Correspondingly, E-cadherin is absent from 2D cells. Moreover, Notch1, a putative stem cell signaling pathway protein that has been shown to promote EMT by snail induction is upregulated in 2D cells compared to 3D, and in response to radiation in both 2D and 3D. It has been reported in some systems that EMT promotion can induce stem cells. The data herein suggest the MDA-IBC-1 maintains pluripotent cells capable of both EMT and stem-like phenotypes. MDA-IBC-1 provides a unique model to examine the interaction between stem cells and EMT and to examine the mechanisms of resistance and proliferation of both cell types.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 103.
Safety of surgery in patients (pts) with locally recurrent (LR) or metastatic breast cancer (mBC) treated with docetaxel (D) plus bevacizumab (BV) or placebo (PL) in the AVADO phase III study.
Authors: Cortés J , Pivot X , Schneeweiss A , Wilcken N , Ellis P , Linderholm BK , Ribelles N , Clemens M , Haslbauer F , Miles DW 
Published: December 2010

Abstract
Abstract #1030
Background: The monoclonal antibody BV (Avastin®) specifically inhibits the biological activity of VEGF to disrupt tumour angiogenesis. The addition of BV to first-line taxane chemotherapy (CTx) increased clinical benefit in two randomised phase III studies of pts with LR or mBC, E2100 and AVADO. It is hypothesised that VEGF is essential for wound-healing, so it is recommended that BV therapy is interrupted prior to surgery and not restarted until the wound is fully healed. Incidence of wound-healing complications and bleeding events was investigated in pts undergoing surgery during the AVADO study.&#x2028; Methods: Pts with HER2-negative, inoperable LR or mBC, no CTx 6 months prior to randomisation (12 months if taxane-based), ECOG PS 0–1, adequate LVEF were randomised to BV (7.5 or 15mg/kg q3w) + D (100mg/m2 q3w for ≤9 cycles) or PL + D until disease progression or unacceptable toxicity. Safety of BV was evaluated in pts undergoing surgery. Major surgery was defined as any surgery requiring opening of a body cavity or more than local anaesthesia.&#x2028; Results: 42 surgical procedures were performed on the ITT population of 736 pts; ranging from minimally invasive procedures to major operations. The number of surgical events was similar in each study arm (PL: 17, BV 7.5mg/kg: 17, BV 15mg/kg: 8). Bleeding and wound-healing events reported in these pts after the date of surgery are presented below.&#x2028; &#x2028; Conclusions: This is the first analysis of the safety of surgery in pts with LR or mBC receiving BV. Treatment with BV + D did not affect the number of pts undergoing surgery. No effect of BV therapy was seen on the frequency of grade 3–5 bleeding and wound-healing adverse events in these pts. BV therapy was interrupted for longer periods pre- and post-major surgery, which may explain why bleeding and wound-healing adverse events are not increased in pts undergoing these procedures. Larger studies are required to obtain a more accurate picture of the safety of surgery in advanced breast cancer pts treated with BV.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1030.
Heterogeneity of gene expression in stromal fibroblasts of breast carcinomas and normal breast.
Authors: Bauer M , Su G , He R , Rehrauer WM , Kendziorski CM , Casper TC , Jonat W , Friedl A 
Published: December 2010

Abstract
Abstract #105
Background: The cancer microenvironment plays a critical role in tumor development and progression. Cancer associated fibroblasts (CAF) constitute a significant component of the tumor stroma and participate in reciprocal communication with the tumor cells. Information on differential gene expression specifically in stromal fibroblasts is sparse and data describing the variability of gene expression in CAF and normal fibroblasts (NF) is currently lacking. The purpose of this study was to identify genes differentially expressed in CAF and matched NF and to analyze the heterogeneity of gene expression profiles in the two cell types.&#x2028; Materials and methods: Fibroblast cell cultures were established from 6 patients with primary invasive breast cancer. Gene expression profiles were generated using oligonucleotide microarrays (Affymetrix HG-U133 Plus 2.0). Differentially expressed genes were ranked using Empirical Bayes modeling. A cut-off value of 0.005 was chosen for the posterior probability of equivalent expression. Lists of overexpressed genes were generated after eliminating genes with less than two-fold overexpression.&#x2028; Results: 17 genes were overexpressed in CAF compared to NF with known functions in paracrine and intracellular signaling, transcription regulation and extracellular matrix production. Using the same posterior probability cut-off, we identified 7 genes which were expressed at least two-fold higher in NF than in CAF. These genes have purported roles in steroid hormone metabolism, transcription, migration and cell signaling. Using semiquantitative RT-PCR and immunohistochemistry, we confirmed the over- and underexpression of a subset of 10 differentially expressed genes. The heterogeneity of gene expression in CAF vs. NF was compared with F-tests to determine variances. The estimated probability of NF gene expression variance being higher than CAF gene expression variance was 0.547 with a 95% confidence interval of 0.543 to 0.551 (p&lt;0.0001), indicating that gene expression is more variable in NF than in CAF. By ranking the q-values of individual genes we identified 3 known genes, which show a significant difference in variance between CAF and NF (p&lt;0.05).&#x2028; Conclusion: Altered gene expression in fibroblasts likely contributes to tumor growth and progression by enhancing ECM production, promoting stromal-epithelial paracrine signaling and altering steroid hormone metabolism. The inter-individual heterogeneity of gene expression in NF may indicate that the mammary stroma varies between individuals, supporting the hypothesis that the ability of the stroma to act as a barrier to cancer development and tumor progression may also be variable. Conversely, the heterogeneous gene expression in NF may be a reflection of a relative synchronization and uniformity of gene expression in CAF.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 105.