bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P1-01-08: Diagnostic accuracy of pre-operative ultrasonographic evaluation of axillary lymph nodes in breast cancer patients: Is there a place for axillary ultrasonography in future nomograms?
Authors: Moorman AM , Bourez R , de Leeuw D , Kouwenhoven EA 
Published: August 2014

Abstract
Background
During the years there has been a significant interest in the development of clinical prediction tools to estimate the risk of having positive lymph nodes in the axilla, and thereby making it possible to plan specific therapies. A non-invasive and widely available method is axillary ultrasonography.
Aim
The purpose of this study was to evaluate the diagnostic accuracy of axillary ultrasonography.
Patients and methods
Between January 2007 and July 2011, pre-operative axillary ultrasonography was performed in 1124 consecutive primary breast cancer patients who underwent surgery with sentinel node biopsy (SNB) and/or complete axillary lymph node dissection (ALND). Suspected lymph nodes (cortex thickness &gt; 2.3 mm) were further analysed by cytology or histology. In case of a negative axillary ultrasonography, standard SNB was performed during operation. In case of suspected lymph nodes with axillary ultrasonography, confirmed by biopsy, routine complete ALND was performed.
Results
Of the 1124 patients, 922 (82%) had unsuspected lymph nodes and 202 (18%) had suspicious lymph nodes during axillary ultrasonography. The sensitivity and specificity of axillary ultrasonography was 46.6% and 93.0% respectively in case of a macrometastases. In all cases of suspected malignancy, axillary core biopsy was performed. The sensitivity and specificity of axillary ultrasonography in combination with core biopsy was 40.5% and 97.2% respectively. With increasing number of axillary nodes the sensitivity increases: 53.9% in case of 2 macrometastases and 83.3% in case of 3 macrometastases.
Conclusion
Ultrasonography and core biopsy are effective in predicting the presence of axillary metastases in breast cancer patients. Especially the high specificity might be of additional value for future nomograms in the surgical treatment of breast cancer patients. In addition, the sensitivity is of greater value in case of gross nodal disease.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-01-08.
Abstract P1-01-13: Intraoperative evaluation of sentinel lymph nodes using touch imprint cytology in patients with early-stage breast cancer: A series of 4367 procedures
Authors: Chen Y , Chen J , Chen J , Yang B , Li L , Huang X , Shao Z , Shen Z , Wu J 
Published: August 2014

Abstract
Background: As the screening for breast cancer becomes common in China, an increasing number of early-stage breast cancer has been detected. For those patients, especially the ones with cliniaclly negetive lymph nodes, sentinel lymph node biopsy (SLNB) plays an important role in the assessment of the axillary status, while minimizing the mobidity of axillary lymph node dissection(ALND). Accurate intraoperative assessment of SLN metastases enables the selection of patients for ALND during the same operation. Touch imprint cytology (TIC) serves as a main intraoperative evaluation of SLNs in our institute since Feb-2005. The purpose of this study is to evaluate its clinical value.
Methods: Early-stage breast cancer patients treated in our institute between Feb-2005 and Apr-2013 enrolled in this study. To avoid breast tissue contamination, all patients had an intraoperative SLNB performed before undergoing lumpectomy or mastectomy. The fresh SLNs were sectioned into 1.5-3.0mm pieces along the short axis, TIC was performed on both surfaces of each piece, its result was correlated with the histological assessments with Hematoxylin-Eosin (H&E) staining, which considered as the gold standard.
Results: A total of 4,367 early-stage breast cancer patients enrolled in the study, and 14,112 SLNs were successfully harvested. Among those, 917 (21.0%) patients were confirmed to have at least one SLN positive for metastases, and 1343 (9.5%) positive SLNs were removed. Based on the final H&E report, the sensitivity, specificity and overall accuracy of TIC was 71.4%, 99.2% and 93.6%, respectively on a per patient basis, and 69.6%, 99.5% and 96.6%, respectively on a per node basis. The sensitivity for macrometastasis and micrometastasis was 74.8% and 26.5%, respectively on a per patient basis, and 78.9% and 25.2%, respectively on a per node basis. To discuss the influence of error results on the surgery procedure, we further reviewed the detail medical records of the patients enrolled in the recent 3 years. Of all the 3290 patiens treated between Jun-2010 and Apr-2013, 207(6.5%) patients needed a second opereation to have the ALN dissected. Meanwhile, 20(0.6%) patients had undergone extra ALND because of the false positive results of TIC.
Conclusion: The sensitivity of TIC seems a little lower then the ones reported previously, but the overall accuracy still remains acceptable. In addition, only 7.1% patients were influenced by the error results of TIC, along with the advantages, such as the shorter preparation time and the less cost of cytological specimens, we consider TIC a feasible method, and believe it can serve well in the intraoperative evaluation of SLNs for early-stage breast cancer patients.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-01-13.
Abstract P1-01-17: Sentinel node biopsy for breast cancer: Intraoperative injection of radiocolloid
Authors: Vu HN , O'Connor PW , Shoemaker RR , Wan W , Fratkin MJ , Bear HD 
Published: August 2014

Abstract
INTRODUCTION. Preoperative injection of radiocolloid for axillary sentinel node biopsy for breast cancer is visibly uncomfortable for many patients. We sought to determine whether injection of the radiocolloid once the patient has been anesthetized would be reliable for sentinel lymph node identification when compared to preoperative injection.
METHODS. A cohort of patients with breast cancer who underwent intraoperative injection of radiocolloid was compared to those who received their injection preoperatively. All injections employed 1mCi 0.5 ml of filtered (0.22 micron) Tc-99m sulfur colloid. All operative surgeons directed injections into the retroareolar tissue; some also intradermally directly over the tumor.
RESULTS. 904 sentinel node biopsy procedures were performed in the six years study period. 759 sentinel node biopsies were analyzed, 664 with preoperative injection of radiocolloid for localization and ninety-five with intraoperative injection. The average age of the patients was 56.8 years: 57.3 years in the preoperative injection group and 53.8 years in the intraoperative injection group. 753 of the 759 patients were women.
Sentinel Node Identification. The overall sentinel lymph node identification rate was similar for the two groups: 94.1% for the preoperative injection group and 93.5% for the intraoperative injection group (P = NS). The identification rate remained equivalent for both groups when analyzed by T stage of the tumor. Similarly, the average number of lymph nodes removed did not differ between preoperative vs. intraoperative injection: 2.66 nodes and 2.55 nodes, respectively.
Sentinel Node Positivity. The overall rate of positive sentinel nodes was also similar for the two groups, 24.7% for the preoperative injection group and 26.4% for the intraoperative injection group (P = NS). When analyzed by T stage, the positivity rate remained similar and not statistically significant. T1 tumors were 21.6% positive in the preoperative group versus 23.9% in the intraoperative group, and T2 tumors were 40.1% vs. 37.0%, respectively.
DISCUSSIONS. Our sentinel lymph node identification rate of 93.5% for the intraoperative injection group appears similar to that of the published literature (96-100%). Our study also showed no statistical difference in positive sentinel node biopsy between preoperative injection (24.7%) and intraoperative injection (26.2%) and is comparable to that of others When analyzed by T stage, our study had 23.9% positive sentinel node biopsies for T1, and 37% for T2 with intraoperative injection.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-01-17.
Abstract P1-01-19: Role of axillary clearance with tumor positive sentinel node in mastectomy group: Is the results of ACOSOG Z0011 trial adaptable to mastectomy patient?
Authors: You JY , Song EJ , Lee MH , Jung SY , Lee SY , Kang HS , Lee ES 
Published: August 2014

Abstract
Background: Recent data from ACOSOG Z0011 trial or AMAROS trial suggest that axillary lymph node dissection(ALND) may be unnecessary for patients with positive sentinel lymph node biopsy(SLNB) receiving breast conserving surgery(BCS) with irradiation. However, consensus statements and guidelines until recently recommended that patients with mastectomy and tumor positive sentinel node undergo completion ALND. In this preliminary study, we compared these patients who did not undergo ALND with the patients who received BCS with SLNB only and irradiation and we analyzed the locoregional recurrence rate to show no differences of outcomes between two groups.
Method: We identified 6,163 women with invasive breast cancer who underwent surgical resection at the National Cancer Center (Goyang,Gyeonggi-do,Korea) between January 2000 to December 2011. Clinico-pathological data obtained from prospective collecting medical database of our institution were analyzed retrospectively. The mastectomy with positive SLNB group was 47 patients and BCS with positive SLNB and irradiation group was 172 patients. The primary end point was loco-regional recurrence rate.
Result : Clinical and tumor characteristics were similar between two groups except T stage and receptor status. The mean tumor size was 5.5cm with mastectomy group and 3.5cm with BCS group. The median number of nodes removed was three. There was not a single case of locoregional recurrence in both groups. At a median follow-up of 53.5 months (last follow-up, May 2013), 5-year overall survival was 85.7% with mastectomy and 97.3% with BCS group.
Conclusion : In our study, there was no case of locoregional recurrence as above. This results lend weight to the argument that SLNB without ALND may be reasonable management for selected patients with appropriate surgery and adjuvant systemic therapy. This study can be regarded as a preliminary study with a sufficient value despite of the prognosis showed some statistical differences between two groups. It resides in the difference of initial stage of patients of two groups. We will present additional data compared with the mastectomy with axillary clearance group at the meeting.
Acknowledgement This work was supported by grant from the National Cancer Center Korea (1210331-2).
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-01-19.
Abstract P1-02-05: Identification of HER-2/neu amplification using amplicon based benchtop next generation sequencing
Authors: Portier BP , Patel K , Medeiros LJ , Singh R , Aldape KJ , Hamilton S , Luthra R , Routbort M 
Published: August 2014

Abstract
Introduction
Aplicon based next generation sequencing (NGS) assays have the potential to incorporate simultaneous assessment of somatic mutations and copy number variation into a single platform. Although not specifically designed for this purpose, we noted numerous examples of apparent HER-2/neu gene amplification in analyzing results from our mutation profiling 46-gene cancer NGS panel (Life Technologies, South San Francisco, CA).
Material and Methods
Existing amplicon coverage data from the TorrentSuite 2.0 (Life Technologies) pipeline was accessed and used to generate a HER-2/neu coverage proportion (ratio between all HER-2/neu amplicon reads and all other amplicon reads). This ratio was calculated for 170 unique cases of breast carcinoma. A total of 4 cases were eliminated from analysis due to indeterminate IHC/FISH results. Using a total of 166 cases, we performed ROC curve analysis to determine the sensitivity and specificity of NGS based HER-2/neu amplification compared to that of traditional IHC and FISH testing (MedCalc v8.0).
Results
The NGS based HER-2/neu coverage proportions in the 166 cases showed a clearly non-normal distribution with an outlier cluster of cases with an elevated NGS HER-2/neu ratio (6 cases with ratios &gt;0.045). The distribution of NGS based HER-2/neu ratios for the entire population ranged from 0.01 to a maximum of 0.34. ROC curve analysis of NGS HER-2/neu proportions compared to IHC/FISH data showed a maximal sensitivity of 75.0% and specificity of 100% at an NGS ratio cut off of ≥0.045.
In the 166 cases, 6 showed a HER-2/neu coverage proportion of &gt; 0.045 (range 0.045-0.34). Utilizing the 0.045 NGS ratio cut off value, the population frequency of cases positive for HER2 expression was 3.4%. Of the 160 samples with NGS coverage proportion &lt; 0.045, only two cases were positive by IHC/FISH testing.
The correlation between NGS HER-2/neu coverage proportion and IHC/FISH testing was highly significant (Spearman rank correlation r = 0.67, p &lt; 0.0001 CI: 0.58-0.75).
Conclusions
Even utilizing a limited somatic cancer panel that includes less than 200 amplicons in 46 genes, clinically significant HER-2/neu amplification can be readily identified. This is the first study to describe the functional utility of HER-2/neu amplification detection using a NGS based amplicon assay. This study shows that in addition to mutation analysis, amplification data can be simultaneously obtained, which has striking implications for potential clinical utility and HER-2/neu amplification detection outside of traditional IHC and HER2 testing modalities. Furthermore, utilizing this assay as a primary screening modality could limit the additional expense of multiple single gene testing.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-02-05.
Abstract P1-02-07: Discordance for low and intermediate levels (1+ or 2+ by IHC) of HER2 protein expression in the phase III PRESENT trial
Authors: Rugo HS , Melisko M , Ben-Baruch NE , Price Hiller J , Dahkil S , Sutton L , Mazanet R , Mittendorf E 
Published: August 2014

Abstract
Background
Significant discordance has been described between different laboratories and between testing methodologies for HER2 overexpression and gene amplification. Concern has focused on missing patients who might benefit from treatment with HER2 targeted therapy. Concordance rates between local and central testing for tumors selected for HER2 0-2+ is not well described. We describe discordance rates between local and central testing performed to identify tumors with 1 and 2+ HER2 expression.
Methods
The PRESENT study is a multicenter, multinational, prospective, randomized, double-blind, controlled Phase 3 study assessing efficacy and safety of the peptide vaccine NeuVax, in HLA-A2 and/or A3 positive patients with early stage, node positive breast cancer expressing low and intermediate levels (1/2+ by IHC) of HER2 protein. PRESENT 2-step screening includes HLA testing followed by central lab confirmation of HER2 1 or 2+ expression using the DAKO HercepTest.
Results
215 patients underwent central IHC testing for HER2. Discordance between local and central testing was seen in 54% (117/215); 34% (65/192) of those eligible by local results were ineligible on central testing, and 48% (11/23) of those not eligible by local results were eligible on central testing.
Local testingCentral testing (IHC (%))IHC (n)01+2+3+0 (15)5 (33%)7 (47%3 (20%)—1+ (127)39 (31%)68 (53%)15 (12%)5 (4%)2+ (65)11 (17%)23 (35%)21 (32%)10 (16%)3+ (8)3 (38%)—1 (12%)4 (50%)
Of those with 1 or 2+ local results, 8% (15/192) were found to be 3+ on central testing. Discordant rates varied by geographic location with higher rates seen in Eastern Europe and Russia.
Conclusion
Significant discordance exists between local and central laboratory test results for HER2 expression by IHC even at lower levels of expression, and current tests are defined by their ability to determine 3+ positivity. In order to improve accuracy of testing and to develop a companion diagnostic for NeuVax, the Leica Bond Oracle HER2 IHC System will be incorporated into future HER2 screening for the PRESENT trial.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-02-07.
Abstract P1-02-08: Papillary lesions of the breast on core biopsies: Should routine surgical excision be performed?
Authors: Ho CS , Yap WM , Chong BK 
Published: August 2014

Abstract
Background: The optimal management of papillary lesions, particularly benign papillomas, detected on core needle biopsies remains debatable. The purpose of this study was to determine the risk of upgrade to malignancy of core biopsy diagnosed papillary lesions on the subsequent surgical excision.
Methods: Following institutional ethics review board approval, the pathology database was searched for all papillary lesions diagnosed on core needle biopsies from Jun 2005 to June 2010. The papillary lesions were histologically categorized as benign, atypical, suspicious for malignancy and definite for malignancy. The core biopsy findings were compared with the follow-up excision biopsy material to identify any upgrade to malignancy (i.e. ductal carcinoma in situ or invasive carcinoma). The presence of any associated significant risk lesions such as atypical ductal hyperplasia (ADH) and lobular neoplasia (LN) were also recorded.
Results: A total of 113 papillary lesions were diagnosed on core needle biopsies of 98 patients, with a mean age of 57 years. A median of 5 cores of breast tissue were obtained per papillary lesion. Of these papillary lesions, 73 were benign, 25 atypical, 8 suspicious for malignancy and 7 definite for malignancy. The overall excision rate was 83%. Of the 58 benign papillary lesions excised, only one (1.7%) showed malignancy (3mm ductal carcinoma in situ) - of interest, the papillary lesion per se was confirmed benign on excision, while an adjacent focus of flat epithelial atypia was present in the initial core biopsy. Nine papillomas were associated with adjacent ADH and/or LN on excision and the rest of the excisions (n = 48) showed no residual papillary lesion or benign papillomas. Among the 24 excised atypical papillary lesions, the positive predictive value (PPV) for malignancy was 42% (10 in situ papillary carcinomas, 4 of these associated with invasive carcinoma). The remaining excisions disclosed ADH and/or LN (n = 3) or benign breast tissue/papillomas (n = 11). None of the 4 papillary lesions with the apocrine atypia were malignant on excision. Of the 5 excised papillary lesions which were suspicious for malignancy on the cores, all showed malignancy (5 in situ carcinomas; 2 associated with invasive carcinoma) on open surgical biopsy. The PPV for malignancy of the 7 core biopsy diagnosed malignant papillary lesions was 100%.
Conclusions: Papillary lesions diagnosed as atypical or suspicious for malignancy on core needle biopsies should be completely excised to exclude malignancy. Our findings suggest, however, that routine surgical excision may not be necessary for core biopsy detected benign papillomas which are not associated with atypia.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-02-08.
Abstract P1-02-10: Variation in HER2 positive rates in California by geographic region: Implications for setting pathology laboratory benchmarks
Authors: Allison KH , Jensen KC , West RB , Clarke CA , Gomez SL , Kurian AW 
Published: August 2014

Abstract
Background: It is unclear how much regional variation there is for HER2 positive rates in breast cancer. By looking at regional variation, we can begin to examine the impact of both demographic variation and pathology laboratory practice on HER2 positive rates so that valid laboratory benchmarks can be established.
Methods: Utilizing data from the California Cancer Registry (CCR), we examined the HER2 positive rates sorted by 58 California counties. Counties were grouped into 10 geographic regions for analysis. Stage at presentation and total numbers of breast cancer cases were studied at as variables. Results: 97,248 breast cancer cases were included in the CCR data. Overall, the HER2 positive rate was 16.5%. HER2 positive rates increased with increasing stage at presentation both overall and by region. Overall they were 12.9% for stage 1, 17.4% for stage 2, 23.2% for stage 3, 25.9% for stage 4 and 25.2% for unstaged cases. There was significant regional variation in overall HER2 positive rates ranging from 13.2-18.9%. 4 regions had overall rates within 0.5% of each other, 3 regions had rates &gt; 0.5% below average and 3 regions had rates &gt;0.5% above average. In the regions with overall rates below the average, one region (region 4, N = 4,636) had lower rates across all stages, and two regions (region 7, N = 8,623 and region 8, N = 14,152) had lower rates only for stages 1-2. Of regions with overall rates higher than the average, one region had increased rates across all stages (region 9, N = 24,279) and two regions had increased rates only in stages 1-3 (region 5, N = 9,176 and region 6, N = 4,888).
Conclusions: In California, there is significant variation in HER2 positive rates by geographic region, even when controlling for stage. The possible influence of differences in regional population characteristics versus differences in laboratory practices to explain this variation should be further examined so that valid regional laboratory benchmarks can be established.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-02-10.
Abstract P1-04-03: Genome-wide analysis of copy number variations and mutation profiles of single circulating tumour cells using massively parallel paired-end sequencing
Authors: Peeters DJE , Kumar P , Van der Aa N , Rothé F , Theunis K , Op de Beeck K , Van Laere SJ , Vermeulen PB , van Dam PA , Vincent D , Desmedt C , Sotiriou C , Dirix LY , Ignatiadis M , Voet T 
Published: August 2014

Abstract
INTRODUCTION
Recent advances in single cell isolation techniques and next generation sequencing (NGS) have paved the way for the genome-wide molecular analysis of individual circulating tumour cells (CTCs) in patients with metastatic carcinomas. Here we present the results of a pilot study evaluating the feasibility and reliability of NGS of single CTC from whole blood samples.
MATERIALS & METHODS
Single cells of the human breast cancer cell line HCC38 were harvested from spiked blood samples in a semi-automated workflow consisting of immunomagnetic enrichment using the CellSearch system and dielectrophoretic cell sorting using the DEPArray system. DNA was isolated and amplified using the Ampli1 whole genome amplification (WGA) kit and subjected to low-coverage genome-wide paired-end sequencing for copy number variation (CNV) analysis and targeted re-sequencing of 200 cancer-related genes for somatic mutation analysis.
RESULTS
Single-cell WGA products of four HCC38 cells were subjected to whole genome sequencing for CNV analysis. Average coverage depth was 0,68x. At a binning window of 50 kb, detection results of CNVs in single-cell samples were highly consistent (&gt;81% copy number concordance per bin genome wide) with CNV profiles from non-amplified multi-cell samples of the same cell line. We could demonstrate that part of the discordance was due to the acquisition of novel DNA-rearrangements in the single cells. Three of the single-cell WGA products were additionally subjected to targeted re-sequencing for mutation analysis of 200 selected genes, of which the analysis is currently ongoing.
DISCUSSION
Our study demonstrates the feasibility of a comprehensive genome-wide CNV analysis and targeted mutation analysis using NGS of single tumour cells isolated from whole blood samples in a highly automated isolation workflow. This approach provides a robust framework for the study of intercellular heterogeneity within the CTC population in blood samples of patients with (metastatic) breast cancer. In addition, our results document the extent of WGA-induced bias of a recently commercialized PCR-based WGA kit.
These authors contributed equally to the data presented in this abstract.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-04-03.