bluuebunny/crossref_metadata_2025_split huggingface dataset:
P3-01-03: The Hominoid-Specific Gene SHON Is Oncogenic in Human Mammary Carcinoma.
Authors: Jung Y , Shastri BG , Kong X-J , Zhu T , Perry JK , Lobie PE , Liu D-X 
Published: June 2012

Abstract
Breast cancer is still the most common malignancy and the leading cause of cancer deaths in both developed and under developed countries. Molecular targeted therapy, in particular monoclonal antibody-based treatment, has emerged as a promising approach to treat this disease because of its high specificity and reduced toxicity. As a consequence, identification of novel molecular therapeutic targets is of crucial importance. In an effort to discover new targets for monoclonal antibody-based targeted therapy, we have identified a novel and secreted hominoid-specific molecule, SHON (secreted hominoid-specific oncogene), in the human mammary carcinoma cell line, MCF-7. Like other hominoid-specific genes, SHON has no known orthologs outside of the primate lineage. It is highly expressed in all cancer cell lines tested so far including breast, lung, liver, stomach, colon and prostate cancer as determined at the mRNA level by RT-PCR and at the protein level by western blotting. Forced expression of SHON in MCF-7 cells significantly increased cell proliferation and survival as demonstrated by 5-bromo-2'-deoxyuridine (BrdU) incorporation and Annexin V/propidium iodide apoptosis assays, respectively. Forced expression of SHON also promoted MCF-7 cell anchorage independent growth in soft agar and enhanced cell migration and invasion. Moreover, forced expression of SHON in MCF-7 cells increased tumour volume in a xenograft model of human breast cancer in immunodeficient mice. Furthermore, depletion of endogenous SHON expression using small interfering RNAs, or functional inhibition using an inhibitory rabbit anti-SHON polyclonal antibody, decreased MCF-7 cell proliferation and survival, and reduced MCF-7 oncogenicity and invasiveness. Therefore, SHON is a novel oncogene for mammary carcinoma cells which may be useful as a therapeutic target for the treatment of breast cancer.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-01-03.
P3-05-05: Cyclin D1 Gene Amplification Is Rarely Heterogeneous in Breast Cancer.
Authors: Burandt E , Grünert M , Choschzick M , Müller V , Bokemeyer C , Simon R , Sauter G , Lebeau A , Jänicke F , Wilczak W 
Published: June 2012

Abstract
Background: Amplification of Cyclin D1 (CCND1) occurs in about 10–20% of breast cancers and has been suggested to predict resistance to anti-hormonal therapy. As the diagnostic accuracy of predictive biomarkers can be substantially limited by regional expression differences within tumors, heterogeneity of CCND1 amplification was assessed in this study. To assess heterogeneity, a novel tissue microarray based analysis platform was developed.
Material and Methods: To comprehensively asses the three-dimensional molecular composition of breast cancers, a “heterogeneity TMA” was constructed containing 8 different tissue cylinders from as many different cancer containing tumor blocks as possible (at least 4) from 147 primary breast cancers. Additional tissue samples were taken from 1–4 corresponding nodal metastases from 35 of these patients. Dual labeling fluorescence in situ hybridization (FISH) with probes for CCND1 and centromere 11 was applied.
Results: The analysis revealed amplification in 29 of 133 (21.8%) patients with interpretable FISH data. CCND1 amplification was more frequently seen in ductal (22 of 87; 25.29%) than in lobular type (5 of 32; 15.63%) (p=0.251). CCND1 amplification was also associated with high tumor grade with amplification rates of 1 of 18 (5.56%) in grade 1, 15 of 72 (20.83%) in grade 2 and 12 of 40 (30%) in grade 3 carcinoma (p=0.075). CCND1 amplification was more frequently seen in ER positive cases (27 of 110; 24.55%) than in ER negative cases (1 of 17; 5.88%) (p=0.052). No association could be found between CCND1 amplification and tumor stage (p=0.445) and CCND1 amplification and PR status (p=0.752). Heterogeneous amplification status was detected in 9 of 29 (31.0%) amplified tumors, i.e. in 6.8% of all informative cases. Heterogeneity was successfully validated on large sections in all 4 heterogeneous cases with high level amplification. In the remaining 5 “heterogeneous cases” discordant results were due to variable interpretation of borderline amplification results with CCND1/centromer 11 ratios between 1.7 and 2.3. There were no discrepancies seen between primary tumors and matched lymph node metastases.
Discussion: The high degree of homogeneity seen for CCND1 amplification suggests that this alteration represents an early event in tumor development/progression in a subset of breast cancers. CCND1 status determined in a small biopsy will be highly representative of the entire tumor and will thus be appropriate for predicting treatment outcome.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-05-05.
P3-07-01: Are the Findings of ASOCOG Z0011 Applicable to District General Hospital Breast Unit – And How Should They Change Our Practice?
Authors: Olsen SB , Amr B , Omar A , Smith J , Thomson S , Monib S , Lai LM 
Published: June 2012

Abstract
Background: There has been considerable debate on the management of the axilla in breast cancer patients with lymph node metastasis found on sentinel lymph node biopsy (SLNB) following publication of the ACOSOG Z0011 study. This study conclude that axillary lymph node dissection (ALND) does not add any benefit to overall and disease free survival in some patients with positive SLNB. However it is not know if the patient characteristics of this study are transferable to other settings. A previous UK study has suggested that only a minority of patients from an academic specialist centre fit the ASOCOG Z0011 criteria and that the patient populations may not be comparable. The aim of our study was to assess the applicability of the Z0011 study to our patient population of a large District General Hospital in the UK and to what extent it should influence our practice.
Methods: The Z0011 eligibility criteria for inclusion in analysis were applied to all patients undergoing SLNB for invasive cancer at West Hertfordshire Breast Unit from 2007–2011. These were: no neo-adjuvant chemotherapy, clinical T1 and T2 tumours, breast conserving surgery followed by whole breast radiotherapy and 1–3 positive nodes on SLNB. Patent characteristics and results were compared using fisher's exact test.
Results: In our unit a total of 434 patients underwent SNLB of whom 64(14.7%) met the inclusion criteria of Z0011. Our patient population was comparable to that of Z0011 with regards to lymphovascular invasion, proportion of patients with micro-metastases and those with additional lymph nodes found on completion ALND. Our patients had significantly more T2 tumours. The only other statistically significant difference was in the proportion of estrogen receptor(ER) and progestrogen receptor (PR) positivity.

Conclusion: Only a small proportion (14%) of patients undergoing SNLB in our patient population fit the criteria for Z0011. This was a higher proportion than in the previous UK study of this type. Similar to this study we found the proportion of patients with T2 tumours were greater in our patient population compared to Z0011. This is most likely a reflection of this unit not being a screening centre and brings in to question the international generalisability of Z0011. However the only other significant difference in our patients was a lower risk profile in terms of hormone rector positivity with more ER/PR positive and fewer ER/PR negative patients. The implications of Z0011, will in our practice, not make a significant difference to the rate of ANLD. We are however considering changing our patient management based on the result of Z0011 and this current study of our population, to offer no further axillary surgery to patients over 50 with T1 and ER/PR positive tumours who otherwise fit the Z0011 protocol.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-07-01.
P3-07-11: Multicenter Comparative Study between One-Step Nucleic Acid Amplification (OSNA) Whole Node Assay and Standard Frozen Section Histology: Intraoperative Molecular Assay for Sentinel Lymph Node Metastases in Early Breast Cancer Can Avoid a Second Surgery.
Authors: Espinosa-Bravo M , Ramos T , Aizpurua Gomez M , Sao Avilés A , Peg Carmara V , Sancho M , Gónzalez-Orus JM , Xercavins Montosa J , Ramos M , Rubio IT 
Published: June 2012

Abstract
Studies on intraoperative assessment of sentinel nodes by frozen section in breast cancer have reported low sensitivity rates. Recently, a molecular-based procedure to detect lymph node metastases, one-step nucleic acid amplification (OSNA) assay, has been developed. OSNA assay can assess a whole lymph node and yields definitive semi quantitative results. The aim of this study was to evaluate the ability of intraoperative assessment comparing sentinel lymph node (SLN) metastases with OSNA assay versus routine H&E frozen section (FS) histology.
METHODS: A cohort of 478 consecutive patients diagnosed in 2010 with early breast cancer in two centers was analyzed. Frozen section was performed intraoperatively in 228 patients and OSNA assay in 250 patients. Patient characteristics were evaluated in both groups and rates of metastasis detected by both methods were compared.
RESULTS: Patients and tumor characteristic are summarized in the table.

A median of 1,95 SLNs were assessed by FS and a median of 2,06 SLNs by OSNA (p=0.15). Intraoperative histopathological assessment detected 67 SLNs metastasis by FS and 107 SLNs metastasis by OSNA assay (p=0.07). There were no differences in rates of macrometastasis (54 by FS and 74 by OSNA) and micrometastasis (13 by FS and 33 by OSNA) (p=0.09). When compared the OSNA assay with permanent section, 92 SLNs had metastasis by permanent section (63 macrometastasis and 29 micrometastasis) with no statistically significant differences (p=0.5).
SLNs metastasis were found in 71 patients (31,1 %) by permanent section and in 83 (33,2 %) by OSNA assay (p=0.69).
Axillary lymph node dissection (ALND) for metastatic SLN was performed in 148 patients, 79 (31,6 %) in OSNA group and 69 (30,2 %) in the permanent section group (p=0.68). All patients diagnosed by OSNA had a complete ALND during the initial surgical procedure. On the other hand, ALND was performed in 51 patients (73,9 %) in the permanent section in the initial surgery, and ALND was performed in a second surgical procedure in18 patients (26 %), due to false negative results of the FS (p&lt;0.001).
CONCLUSIONS: The OSNA assay can detect SLN metastasis as accurately as conventional pathology, with no increased detection of positive SLNs. Given the definitive pathology of the SLN intraoperatively, the use of OSNA can reduce the need for a second surgery in 26 % of patients with breast cancer and a positive SLN.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-07-11.
P3-07-13: Validation and Comparison of Models To Predict Nonsentinel Lymph Node Metastasis in Chinese Breast Cancer Patients with Positive Sentinel Lymph Nodes.
Authors: Chen K , Jia W , Zeng Y , Fan M , Su F , Li S 
Published: June 2012

Abstract
Background: Several models for predicting the risk of nonsentinel lymph node (NSLN) metastasis in breast cancer patients with positive sentinel lymph nodes (SLNs) have been developed. Independent validation of these models in different populations is necessary before clinical application. This study aimed to validate and compare these models in Chinese patients.
Patients and Methods: A total of 159 breast cancer patients with positive SLNs treated at our institution were included. Chi-squared tests, RP-ROC, CART and multivariate logistic regression were used to analyze the risk factors for NSLN involvement in our population. ROC curves, calibration plots and false-negative (FN) rates were evaluated for 11 reported models. The threshold of each model for classifying patients into the low-risk group was adjusted to render the FN rate close to 10%.
Results: In total, 81 (50.9%) patients had at least one NSLN involvement. Univariate and multivariate analyses revealed that the number of negative SLNs (P&lt;0.01, HR=0.63) and the metastasis size of the positive SLNs (P&lt;0.01, HR=1.15) independently predicted the NSLN status in our population. The Cambridge and Mou models outperformed the others, both with AUCs of 0.73. The other models performed as follows: the Mayo, Tenon, MDA, MSKCC, Ljubljana, SNUH and Louisville models had AUCs of 0.68, 0.66, 0.66, 0.64, 0.62, 0.61 and 0.60, respectively. The Stanford and Saidi models did not present any discriminative capabilities, with AUCs of 0.54 and 0.50, respectively. The Cambridge, MSKCC and Mayo models were well calibrated. The Ljubljana model did not calibrate well.

With adjusted thresholds, the Mayo model outperformed the others by classifying the highest proportion of patients (20%) into the low-risk group. The Cambridge, Mou and MDA models defined 17.0%, 14.5% and 15.1% of patients as low-risk, respectively.

Conclusion: The Cambridge and Mou models performed well in Chinese patients. ROC curves, calibration plots and FN rates should be used together for the accurate evaluation of prediction models. The analysis of the clinicopathological features of the targeted population is critical for the selection of the most appropriate model. The models specifically designed for patients with micrometastases or macrometastases of SLNs are needed in the future.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-07-13.
P3-07-15: Sequential Peri-Areolar and Peri-Tumoural SPECT/CT Lymphoscintigraphy Has Identified High Rates of Discordance in Both Axillary and Internal Mammary Sentinel Lymph Node Mapping.
Authors: Noushi F , Spillane A , Gebski V , Snook K , Gillet D , Cooper R , Allwright S , Uren R 
Published: June 2012

Abstract
Introduction: The release of the MA20 intergroup trial results has confirmed the importance of locoregional radiation on local and distant disease control and survival. Sentinel lymph node (SLN) evaluation is the gold standard for regional lymph node evaluation and radiation oncologists continue to utilize the nodal staging to plan adjuvant locoregional therapy. Despite over a decade of experience in SLN evaluation there persists a common belief that the lymphatic drainage of the whole breast is to anteropectoral axillary lymph nodes. Several different lymphoscintigraphy injection techniques are in use with claims that they all identify the same axillary sentinel nodes. However this is not based on a high level of evidence. The evolution of SPECT/CT has led to the accurate anatomic identification of SLN, hence the different lymphoscintigraphy techniques can now be directly compared.
Method: 38 patients underwent double sequential lymphoscintigraphy (peri-areolar followed by peri-tumoural) separated by 1–7 days. Patients were referred by 4 surgeons to 3 separate lymphoscintigraphy centres with standardisation of tracer substance (99mTc-antimony sulfide colloid), lymphoscintigraphy and SPECT/CT evaluation techniques. The degree of discordance in sentinel node evaluation was defined as:
Type 1 - One study demonstrates SLN(s) in a nodal basin [axilla or internal mammary chain (IMC)] and the other study demonstrates none. Type 2 - Both studies identified SLN(s) in a nodal basin however the SLN(s) are all different. Type 3 - Both studies identified SLNs in a nodal basin, however some SLN(s) are identical and others not.
Results:

Notably 21 patients (55%) had either axilla or IMC lymphoscintigraphy discordance. Two patients had both axilla and IMC lymphoscintigraphy discordance.
The majority of discordance was identified in the IMC. In the concordant IMC lymphoscintigraphies neither study demonstrated IMC SLN. There were no studies that identified identical IMC nodes in both PA and PT lymphoscintigraphy.
Discordant axillary drainage was more evident in patients with lateral sector tumours compared to IM discordance with medial sector tumours.
Conclusions: Accurate lymphoscintigraphy is the road map to assist a surgeon identify lymph node metastases. In turn accurate staging will determine appropriate adjuvant therapy decisions particularly regional node irradiation. This study demonstrates a high degree of discordance between PA and PT lymphoscintigraphy techniques in 55% of patients. Inadequate lymphoscintigraphy can result in unrealized false negative results, which could impact patient outcomes and clinical trial results.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-07-15.
P3-07-27: ROCK II Expression Can Be a Potential Marker of Non-Sentinel Lymph Node Metastasis in Breast Cancer Patients with Sentinel Lymph Node Involvement.
Authors: Shigematsu H , Taguchi K , Shiotani S , Kawaguchi H , Nishiyama K , Ohno S , Okada M 
Published: June 2012

Abstract
(Background) It becomes controversy whether axillary lymph node dissection is mandatory performed for breast cancer patients with positive sentinel lymph nodes (SNs), given that more than half of patients with a positive sentinel lymph biopsy have no metastasis in non-sentinel lymph nodes (non-SNs). Rho-associated kinase (ROCK) is essential part in tumor invasion and metastasis, and its activation is reported to be potential marker of lymph node metastasis.
(Purpose) The purpose of this study was to evaluate the expression of ROCK II as predictive factor of non-SNs metastasis in breast cancer patients with positive SNs.
(Patients and Method) ROCK II protein expression was determined using immunohistochemical analysis on formalin-fixed and paraffin-embedded primary tumor samples composed of 119 SN-positive patients who underwent axillary lymph node dissection in National Kyushu Cancer Center. ROCK II expression was defined positive when there was strong intensity of cytoplasm staining.
(Results) ROCK II expression tended to be strong in invasive area, but weak in intraductal component. Of the 119 patients, 35 (29%) were determined to be positive for ROCK II expression. Patients with ROCK II positive tumor had significantly higher probability of non-SNs metastasis compared with patients with ROCK II negative tumor (20/35, 57% for positive; 28/84, 33% for negative, p=0.02). In multivariate analysis, positive ROCK II expression was significantly associated with non-SNs metastasis even after accounting for other predictive factors including tumor size, lymphovascular invasion, number of SNs metastasis and extra-capsule invasion (positive vs. negative, HR 2.6, p=0.04).

(Conclusion) These findings suggest that ROCK II expression can be a predictive factor for non-SNs involvement in breast cancer patients with SNs metastasis.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-07-27.
P3-07-32: The Role of Axillary Ultrasound in the Detection of Metastases from Primary Breast Cancers.
Authors: Yamashita M , Little E , Fraley J , Hovanessian-Larsen L , Sener SF 
Published: June 2012

Abstract
Background: The value of ultrasound (US) in the preoperative evaluation of axillary nodes has yet to be completely clarified. Preliminary experience with this technique in our institution was examined.
Methods: Patients with a radiographic or palpable abnormality of the breast had simultaneous breast and axillary US. The exams were performed by dedicated breast radiologists using a 12 MHz linear array transducer (HDI 5000: Philips Ultrasound). Results were reviewed for all patients with invasive cancers who were cN0 and had definitive surgical procedures between June 2006 and May 2008. Criteria for abnormal lymph nodes were loss of reniform shape, focal or diffuse cortical thickening, or eccentric/replaced fatty hilum. US-guided biopsies were done using a 16g spring-loaded core biopsy device (16g MD TECH SuperCore). Patients with positive axillary node biopsies bypassed sentinel lymph node biopsy (SLNB) and had axillary dissection, whereas those with sonographically normal nodes or benign/non-diagnostic biopsy results had SLNB at the time of definitive surgery.
Results: Of 128 patients diagnosed with invasive cancer, 23 (18%) had abnormal axillary US at the time of initial diagnosis. Biopsies were performed in 18 of the 23, of which 12 (67%) were malignant and 6 (33%) were benign. Ultrasounds were negative in 105 (82%) patients. SLNB was done in 110 patients: 103 with negative US; 4 patients with abnormal US but negative axillary biopsies; 2 patients with abnormal US but no core biopsies; and 1 patient with a positive US biopsy. SLNB was negative in 91 (83%) patients and positive in 19 (17%). The node-positive status was N1a in 14 patients and N1mic in 5. Axillary dissection was done in 32 (25%) of 128 patients, comprised of 11 patients with US-guided positive biopsies, 12 with positive sentinel nodes, 2 with US-guided negative biopsies, 2 with negative ultrasounds, 3 with unbiospied abnormal ultrasounds, and 2 with a false-negative SLNB. For determining axillary metastases with US, sensitivity was 16/31 (52%), specificity was 90/97 (93%), positive predictive value was 16/23 (69%), and negative predictive value was 90/105 (86%).
Conclusions: US examination was a valuable method of evaluating the axilla in newly diagnosed breast cancers. Of 32 patients having an axillary dissection, abnormal US eliminated the need for SLNB in 17 (53%). Patients with US-guided positive nodes were submitted to axillary dissection without SLNB. Therefore, we were unable to determine how often US identified an abnormal non-sentinel node, thus upstaging the axilla relative to SLNB alone. This question should be the topic of further clinical study.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-07-32.
P3-07-34: Occult Metastasis in Sentinel Node: Should This Affect the Clinical Decision Making? A Systematic Review and Meta-Analysis.
Authors: Valachis A , Nearchou A , Polyzos NP , Lind P , Berqvist J 
Published: June 2012

Abstract
Background: The role of occult metastases (micrometastasis or isolated tumor cells [ITC]) in sentinel lymph nodes (SLN) remains a field of debate and speculation. The purpose of this systematic review and meta-analysis was to investigate the prognostic relevance of occult metastases in SLN.
Methods: We searched PubMed, without year or language restriction through June 2011, for studies on patients with invasive breast cancer with micrometastasis or ITC in the SLN and presented Hazard Ratios (HR) on Overall Survival (OS) / Disease-Free Survival (DFS) or enough data for HR-calculation. We used fixed- or random-effects meta-analyses, as appropriate, to calculate pooled estimates of HR. Results: Fifteen studies were considered eligible. Of those, 3 studies were excluded due to the lack of data for HR-calculation. Both the presence of ITC (5 studies; 1264 patients with ITC) and micrometastasis (10 studies; 1093 patients with micrometastasis) were associated with worse DFS (pooled HR 1.29, 95% Confidence Interval [CI]: 1.09−1.52, P-value = 0.002 for ITC, pooled HR 1.45, 95% CI: 1.28−1.64, P-value &lt; 0.001 for micrometastasis). No significant differences were observed regarding OS neither for the presence of ITC (5 studies; 877 patients with ITC; pooled HR 1.20, 95% CI 0.98−1.46) nor for micrometastasis (8 studies; 1094 patients with micrometastasis; pooled HR 1.36, 95% CI: 0.98−1.88).
Conclusion: Based on the current evidence, it seems that the presence of occult metastasis in SLN is of prognostic significance in regard to DFS. However, the clinical significance of this difference is questioned since it cannot be translated into differences in OS. In anticipation of randomized trials aimed to evaluating the optimal management of each category of tumor burden within SLN, current evidence suggest a limited clinical significance of occult metastases in SLN.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-07-34.