bluuebunny/crossref_metadata_2025_split huggingface dataset:
P3-03-04: Targeted Modulation of HER Receptor Signaling in Breast Cancer Using miR-21.
Authors: Aubele M , Ludyga N , Braselmann H , Atkinson MJ , Auer G , Anastasov N 
Published: June 2012

Abstract
Introduction: MicroRNAs (miRNAs) are multifunctional nucleic acids that regulate the stability and translational efficiency of targeted messenger RNAs. Endogenously altered miRNA levels have been linked in breast cancer to acquired chemoresistance and changed radiosensitivity. Thus the modification of miRNA expression represents an attractive therapeutic strategy. We now show that the targeted inhibition of miR-21 can modify expression of the HER2 receptor in breast cancer.
Materials and Methods: Using TaqMan-based technology the expression of five selected miRNAs (miR-7b, miR-10a, miR-17-5p, miR-125a, and miR-21) was investigated in formalin-fixed, paraffin-embedded breast carcinoma tissues expressing different levels of HER2 (n=60). Possible regulation of HER2 was explored in cell lines using lentivirus to stably downregulate or upregulate HER2 and miR-21 expressions. The effects were analyzed using qRT-PCR, Western blots, proliferation and migration assays.
Results: In tumor tissues we identified overexpression of miR-10a and miR-21, and underexpression of miR-17-5p and miR-125a in most of the tumor tissue samples. Significant associations (p≤0.05) were found between HER receptor expression and the expression of miR-17-5p and miR-125a, and miR-21 showed correlation with expression of ER and PR. Furthermore, analysis of miR-21 downregulation in breast cancer cell lines showed inhibition of cellular proliferation and HER2 protein synthesis. Additionally, downregulation of HER2 expression decreased miR-21 expression and showed moderate change in cellular proliferation activity.
Conclusions: Based on these results we conclude that there is tight interplay between HER2 and miR-21 expression in breast cancer cells. Because miRNAs modulate gene expression we suggest that modulation of miR-21 has the potential to impact tumor therapy by interference with specific signaling pathways.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-03-04.
P3-04-02: Bevacizumab Treatment Alters Intrinsic Subtypes in a VEGF-Reinforced Xenograft Model of ER-Positive Breast Cancer.
Authors: Gökmen-Polar Y , Toroni RA , Goswami C , Sanders KL , Sirimalle U , Mehta R , Li L , Ivan M , Badve S , Sledge GW 
Published: June 2012

Abstract
Background: Anti-vascular endothelial growth factor (anti-VEGF) therapy improves disease-free but not overall survival in metastatic breast cancer. To seek further insight on resistance to anti-VEGF antibody bevacizumab (BEV) at the molecular level, we developed breast cancer xenograft models allowing comparison of tumor response at different time-points. Here we report the gene expression and miRNA analyses of response and non-response to BEV in these models.
Methods: MCF-7 cells transfected with control vector (ML20) or VEGF (MV165) were implanted into the mammary fat pads of athymic mice. Tumors from short-term treatment with BEV (3 weeks; Responders to BEV, R) or long-term treatment (8 weeks; Non-Responders, NR) or with vehicle control group (V) were subjected to whole-genome gene expression analysis (Human WG-6v2 Expression Beadchips, Illumina) and miRNA profiling (TaqMan ArrayHuman MicroRNA A+B Cards Set v3.0, Applied Biosystems).Validation of the chosen genes was performed using quantitative real-time RT-PCR (qRT-PCR) and Immunohistochemistry (IHC). Results: Short-term treatment to BEV (3 weeks; 5 mg/kg, i.p./twice weekly) inhibited primary tumor growth significantly in MV165 xenografts compared with vehicle control, whereas BEV treatment did not affect the tumor growth in the ML20 model. MV165 xenografts progressed after 8 weeks of BEV treatment. Gene set enrichment analysis (GSEA) revealed that luminal A-related gene sets were enriched in MV165-R compared to MV165-NR group including DESMEDT (ESR1), SMID_Breast_Cancer_Luminal_A_up, and MASSARWEH_ Tamoxifen_Resistance_ Down. Myoepithelial-specific gene sets were upregulated in both the R and NR groups compared with the vehicle group. qRT-PCR analysis showed that estrogen receptor alpha (ESR1) representative for luminal A decreased significantly in the MV-165-NR group (P=0.001) compared to vehicle. In contrast, Cytokeratin 5 (KRT5) levels increased significantly in both R (P=0.02) and NR (P=0.03) groups. In addition, KRT14 was upregulated in R (P= 0.04) and in NR (P=0.14) group in comparison with the vehicle group, suggesting the upregulation of myoepithelial phenotype specific to BEV treated MV165 model, but not ML20 model. Similar results were obtained by IHC. Consistent with mRNA changes, ESR1 regulated miRNA such as miR-107 (P=0.007) and miRNA important in tamoxifen resistance such as mir-451 (P= 0.0003) were also altered in MV165-NR group compared to vehicle. Conclusion: These results suggest that treatment with BEV may alter the intrinsic subtypes in the presence of VEGF expression. These data may help to explain the variable results to anti-VEGF therapy based on the duration of BEV treatment.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-04-02.
P3-05-04: Changes in Recurrence Risk of Breast Cancer Intrisic Subtypes over Time.
Authors: Ribelles N , Perez-Villa L , Pajares B , Jerez JM , Vicioso L , Jimenez B , de Luque V , Franco L , Alvarez M , Perez-Rivas LG , Sanchez-Muñoz A , Gallego E , Marquez A , Hierro I , Alba E 
Published: June 2012

Abstract
Background: Gene expression profiling and their immunohistochemistry-based surrogates have consistently revealed prognostically significant breast cancer (BC) subtypes: Luminal A (Lum A), Luminal B (Lum B), HER2, Basal-like (BL) and Triple negative phenotype-nonbasal (TNP-nb). In addition, there are clinical evidence that hazard of BC recurrence varies over time with two peaks of high risk at 18–24 and 60 months. This study compares the time-related patterns of recurrence within BC subtypes. Methods: Tissue microarrays were constructed from 937 early BC patients diagnosed and treated at our Hospital from 1982 to 2005 with available archival paraffin tissue blocks. BC subtypes were defined using an immunopanel of estrogen receptor, progesterone receptor, HER2, epidermal growth factor receptor, cytokeratin 5/6 and Ki67 by prespecified published methods. Univariate and multivariate analysis (Cox regression) were performed on progression-free survival. Smoothed curves for hazard rates (HR) were estimated by a Kernel-like smoothing procedure. The statistical analysis was done by using the R software environment.
Results: Cases were classified as follows: Lum A 46.8%, Lum B 25.2%, HER2 11.3%, BL 11.3%, TNP-nb 5.4%. None of the patients were treated with adjuvant trastuzumab. With a median follow up of 80 months age, tumor size, nodal status and intrinsic subtypes were independent prognostic factors. HER2 and BL show high and early peak in HR curves and decreasing sharply to 36 and 48 months respectively. HR in Lum A, Lum B and TNP-nb exhibit a smoother and nearly steady curve.

Conclusions: BC subtypes have distinct outcome but also displays different pattern of recurrence over time. These data might imply that pathways underlying early and late recurrences could be different. This additional information would suggest the convenience of considering different timings and duration of adjuvant treatments depending of BC subtypes, and also in the design of surveillance recommendations.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-05-04.
P3-05-09: Comparison of Clinical Features and Patterns of Recurrence in Triple Negative Breast Cancers in Relation to Other Breast Cancers.
Authors: Tosello de Oliveira C , Barbosa EM , Costa de Andrade J , Lyra EC , Felzener MC , Krutman Zveibil D , Grosso SHG , Sampaio Goes de Oliveira R , Sampaio Góes JC 
Published: June 2012

Abstract
Background : Breast cancer is an heterogeneous disease that have several and different biological characteristics and clinical behaviours. Of these, triple negative breast cancer represents 10–17%.This kind of tumor is characterized by estrogen, progesterone and HER2 receptor negativity and they are very aggressive, associated with poor prognosis, younger patients, high incidence of metastases and shorter relapse free survival. Triple negative breast tumours are more likely to experience local recurrence and distant relapse than other breast tumors, and require a more aggressive intervention.
PURPOSE : To compare the incidence of metastases, clinical features and outcome among patients with triple negative breast cancer and women with other types of breast cancer.
METHODS : This is a retrospective cohort analysis from 3893 patients with invasive breast cancer, diagnosed between January 2000 and April 2011 and attended at Brazilian Institute of Cancer Control (IBCC) in Sao Paulo, Brazil. Five hundred of these tumors were triple negative. We made a correlation of clinical variables such as age, tumor stage (TNM) and analysis of last follow-ups, such as metastases, disease free survival, death for tumor, death for other reasons, lost of follow-up, hygiene and diet regime (RHD) and local recurrence.
Results: The median follow-up for the cohort was 4,29 years. The mean age at diagnosis in triple negative group was 54,8 and for the others group was 57,1 years. Subgroup analysis of tumor grade showed that the triple negative breast tumors were diagnosed later (Stage II and III; p:&lt;0,0001). There was no difference in the appearance of the two types of tumors, when considering diagnose age. The incidence of metastases, death for tumor and free survival in triple negative tumors, respectively; 25,6%, 13,8% and 57,2% (p:&lt;0,0001) demonstrates the aggressiveness of this kind of tumor.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-05-09.
P3-06-05: Comparison of Oncotype DX® Recurrence Scores between Surgical and Core Biopsy Specimens in Breast Cancer Patients.
Authors: Stull TS , Goodwin MC , Anderson JM , Baehner FL , Sing AP , Yoshizawa CN , Barrio AV , Frazier TG 
Published: June 2012

Abstract
Introduction: The Oncotype DX® 21 gene assay is usually performed on surgical resection specimens (SRx) for patients (pts) with early stage, estrogen receptor positive (ER+) breast cancer to predict the risk of recurrence and likelihood of benefit from adjuvant chemotherapy (CT) and hormonal therapy (HT). Using the Recurrence Score (RS) to aid in making a decision to administer preoperative CT requires assaying the core biopsy specimen (CBx). The objective of this study is to compare the RS obtained from paired CBx and SRx specimens. Methods: 25 pts with invasive breast cancer diagnosed by CBx with a subsequent Oncotype DX® 21 gene assay performed on the SRx were identified. Fixed, paraffin embedded tissue from these paired CBx were sent to Genomic Health. The H&E slide from the paired SRx sample sent for the RS was used to compare the histology with the paired CBx. The RS from the CBx and SRx pairs were examined descriptively with scatterplots and Pearson correlation coefficients.
Results: Median age of diagnosis was 64 (range 39–78). Sufficient RNA was obtained from all but 1 of the CBx. H&E from CBx and SRx were histologically dissimilar for 3 of 24 pairs with RT-PCR data. The Pearson correlation for RS between CBx and SRx was 0.83 (95% CI 0.64, 0.92) for all 24 pairs. The distribution of RS groups from CBx was 19 low (RS&lt;18), 3 intermediate (RS 18–30), 2 high (RS&gt;31). The RS group from SRx was unchanged for 22 (92%) pts. Two pts switched RS groups, CBx RS 5 to SRx RS 18 and CBx RS 8 to SRx RS 24; only the latter is clinically meaningful because the former straddles the low-intermediate cutpoint. Correlations between CBx and SRx for individual single gene scores were 0.84 (95% CI 0.65, 0.93) for ER, 0.83 (95% CI 0.64, 0.92) for PR, and 0.82 (95% CI 0.61, 0.92) for HER2. Similar results were obtained excluding the 3 histologically dissimilar pairs.
Conclusion: The RS's obtained from CBx's were consistently similar to the RS's obtained from the paired SRx. Using an RS obtained from a CBx in pts with ER+ disease to make a decision regarding neoadjuvant CT or HT is clinically acceptable, thus, giving physicians an additional tool to improve pt care and outcomes.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-06-05.
P3-07-03: One-Step Nucleic Acid Amplification (OSNA) for the Diagnosis of Sentinel Lymph Nodes of Breast Cancer – Results of the China Multicenter Study CBCSG-001c.
Authors: Wang YS , Ouyang T , Wu J , Liu YH , Cao XC 
Published: June 2012

Abstract
Background
With the adoption of sentinel lymph node (SLN) biopsy as the standard of care, there is an increasing need for the rapid and accurate intra-operative diagnosis of SLNs. CBCSG-001c was a prospective multicenter trial to validate the One-step nucleic acid amplification (OSNA) assay in China. The primary endpoint was the concordance rates of intraoperative OSNA assay with the in-depth permanent histological analyses based both on cases and SLNs.
Methods: From Feb. to Dec. 2010, 1188 SLNs from 552 breast cancer patients were enrolled in the CBCSG-001c study at 5 centers. SLNs were cut into alternating ∼2mm sections. One half of the sections were sampled for H&E, with 4 sections at different intervals. The other half was fully tested with the OSNA assay. Predetermined cutoffs were calibrated so only metastases &gt;0.2 mm were detected.
Results: The concordance rate was 89.1% (95% CI, 86.3−91.5%), sensitivity 87.7% (95% CI, 81.0−92.7%), and specificity 89.6% (95% CI, 86.3−92.4%) based on 552 cases, and the concordance rate was 91.4% (95% CI, 89.7−92.9%), sensitivity 83.7% (95% CI, 77.7−88.6%), and specificity 92.9% (95% CI, 91.1−94.4%) based on the 1188 SLNs. This quantitative molecular assessment allows the distinction of the size of the metastasis, and the PPV of OSNA [++] for macrometastases was 83.2% (95% CI, 75.0- 89.1%). Discordant results were thought to be partly due to the fact that different tissue sections were used for OSNA assay and histology, and SLNs with ITCs were not considered as histological positive nodes. After discordant case investigation, the senstivity of OSNA assay was significantly higher than that of intraoprative frozen section and touch imprint cyctology.
Discussion: As the largest OSNA study to date, our results, together with that of Japan, Germany, and France study, proved the OSNA assay based on CK19 mRNA expression to be a reliable and standardized tool for the intraoperative detection of SLN metastases of breast cancer patients as compared to in-depth permanent histology. The high sensitivity of OSNA assay means reducing the risk of second operation for ALND, medical care costs and patients anxiety.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-07-03.
P3-07-10: Sentinel Lymph Node Navigation Surgery Using Combination of Indocyanine Green Fluorescence and Blue Dye for Breast Cancer Patients.
Authors: Takahashi M , Hayashida T , Jinno H , Kitagawa Y 
Published: June 2012

Abstract
Background: Sentinel lymph node (SLN) biopsy is now widely accepted for staging the axilla in breast cancer patients. Several methods are presently used to detect SLNs. Combined use of blue dye and radiocolloid has previously been described as a superior method for detecting SLNs in breast cancer patients, but radiocolloid is not generally available in Japan. SLN detection guided by indocyanine green (ICG) fluorescence could emerge as a new and effective method for SLN biopsy. The aim of this study was to evaluate SLN biopsy using combination of ICG fluorescence and blue dye methods for breast cancer patients.
Material and Methods: We enrolled 75 patients with clinically node-negative breast cancer. An isosulfan blue dye solution (5ml) was injected subcutaneously just above the tumor and in the periareolar area after the induction of anesthesia. The injection site was massaged for five minutes and ICG (2ml) was then injected subcutaneously just above the tumor and in the periareolar area before starting the surgical procedure. Subcutaneous lymphatic channels draining from the areola to the axilla were visualized with a fluorescence imaging system (Photodynamic Eye: PDE, Hamamatsu Photonics Corporation, Japan) under fluorescence within several minutes. SLNs were dissected under direct visualization supported by fluorescence and dye navigation and diagnosed by intraoperative frozen section with hematoxylin and eosin staining. Any patient with a positive SLN underwent immediate axillary lymph node dissection (ALND).
Results: SLNs were detected in all 75 patients. The fluorescence imaging identified 2.6 SLNs in 74 (98.7%) of 75 patients. The blue dye identified 1.6 SLNs in 68 (90.1%) of 75 patients. Twelve of the 75 (16.0%) patients had metastatic SLNs and ALND was immediately performed. No metastasis revealed in any non-SLN in eight of these 12 patients. Metastatic SLNs were detected by the ICG fluorescence and not by blue dye in four of these 12 patients. Discussion: The combination of ICG fluorescence and blue dye method had two advantages: it could reveal lymph flow on the surface before we determined the skin incision line; and it had a high SLN detection rate. In hospitals where radioisotopes are unavailable, a combination of the two methods would be advantageous.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-07-10.
P3-07-16: The Efficacy of Arm Node Preserving Surgery Using Axillary Reverse Mapping for Preventing Lymphedema in Patients with Breast Cancer.
Authors: Seo YJ , Hwang MJ , Lee JH , Son GT , Choi JE , Bae YK , Kang SH , Lee SJ 
Published: June 2012

Abstract
Background
Lymphedema affects over 20% of breast cancer patients undergoing axillary dissection. Axillary reverse mapping (ARM) technique to identify and preserve arm node during sentinel lymph node biopsy (SLNB) or axillary lymph node dissection (ALND) was developed to prevent lymphedema. The purpose of this study was to investigate the location and the metastatic rate of the arm node, and finally to evaluate the short term incidence of lymphedema after arm node preserving surgery.
Patients and Methods
From January 2009 to October 2010, 97 breast cancer patients who underwent ARM were enrolled. 2.5ml blue dye was injected in ipsilateral upper inner arm. After at least 20 minutes after injection, SLNB or ALND was performed in the usual manner and blue stained arm nodes and/or lymphatics were identified. We checked arm circumference at baseline and average of 8.8 months after operation in ALND cases and 13.7 months in SLNB cases. Patients were divided into two groups, arm node preserved group (70 patients in ALND, 10 patients in SLNB) and unpreserved group (13 patients in ALND, 4 patients in SLNB). The difference of arm circumference between preoperative and postoperative was checked in these groups.
Results: The mean number of identified blue stained arm nodes was 1.4±0.6. The arm nodes were found in the inferolateral side of axillary and thoracodorsal vessels in 57 patients (58.76%), the inferomedial side in 37 patients (38.14%), the superolateral side in 2 patients (2.06%), and the superomedial side in 1 patient (1.04%). In the majority of patients (92%), arm nodes were located between the lower level of the axillary vein and just below the second intercostal brachial nerve.
In arm node unpreserved group, 2 patients had metastasis in their arm node. The one had a common pathway between the arm node and the sentinel lymph node. Another did not have a common pathway, but had extranodal extension with N3 metastasis. Among ALND patients, in arm node preserved group, the difference of arm circumference between preoperative and postoperative in ipsilateral and contralateral arm was 0.27cm and 0.07cm, respectively, whereas 0.47cm and −0.03cm in unpreserved group, and one lymphedema was found after 6 months. No difference was found between arm node preserved and unpreserved group amoung SLNB patients (0.21cm and 0.39cm in in preserved group, 0.2cm and 0.02cm in unpreserved group).

Conclusion: Arm node preserving was possible in all breast cancer patients with identifiable arm node, during ALND or SLNB, except for those with high surgical N stage, and lymphedema did not developed in patient with arm node preserving surgery. Metastasis was not found in arm node preserving group in current results, but need to be observed in the ongoing progress.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-07-16.
P3-07-31: Intra-Operative Assessment of Sentinel Lymph Nodes in Breast Cancer with Touch Imprint Cytology (TIC) in 460 Consecutive Patients.
Authors: Iqbal M , Shetty G , Randhawa S , Sandhu F , Chachlani N , Simon J , Harries S , Jones L , Clarke D 
Published: June 2012

Abstract
Background
Sentinel node biopsy (SNB) accurately predicts the axillary lymph node status in patients with breast cancer. The sentinel lymph node (SLN) is evaluated by routine histology, requiring 3–5 days for the results and a second operation if the SLN is positive. However a second operation can be avoided if a reliable intraoperative assessment of the SLN was available. The techniques used for intra-operative assessment of the SLN include frozen section, touch imprint cytology (TIC) and more recently molecular biology assays. The aim of this study was to evaluate the accuracy of TIC in the assessment of the SLN.
Methods: A prospective study to include 460 patients with breast cancer who underwent SNB and had the sentinel node assessed intra-operatively with TIC. The SLN was bisected and a touch imprint was made on to a slide. The imprint was stained with Giemsa stain. Permanent sections were evaluated with H&E and immunohistochemical staining. The TIC results were compared with the final histology of the SLN.
Results: 766 SLN's were harvested from 460 patients (Mean - 1.66). Of the 460 patients, TIC was falsely negative in 50(24%) patients. No patients had false positive results. Negative predictive value was 87%. The accuracy rate was 89%. 94 patients were positive on histology. TIC was positive in 44 patients and negative in 50. The sensitivity, specificity and positive predictive value of TIC was 47%, 100% and 100% respectively. By acting on the results of TIC, 44 patients (47%) had an axillary clearance at the primary operation and were thus spared a second operation.
Conclusion: TIC in our cohort of 460 patients and 766 sentinel lymph nodes had an accuracy rate of 89% and specificity of 100%. Our study compares favourably with published literature, confirming that TIC is a simple, quick, reliable and reproducible technique that can be used for intra operative assessment of the SLN. A sensitivity of 47% means that about half of the SLN positive patients were spared a second operation. We had hoped that with more experience, our sensitivity would improve but since this has not been the case we are now moving towards molecular biology assays (OSNA) to assess the SN intra-operatively.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-07-31.