bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P3-10-21: Audit of the Accuracy of Immunohistochemical (IHC) Testing of HER2 Status of Breast Cancer in the United Kingdom: An Interim Analysis
Authors: Starczynski JL , Campbell FM , Jones P , Gilbert J , Dowds JC , Miller K , Ibrahim M , Jasani B 
Published: April 2011

Abstract
Background: The analysis of the level and distribution of HER2 protein expressed by cancer cells (HER2 status) is of great clinical value in the management of breast cancer patients both for the determination of the prognosis of disease and for identification of those patients who are eligible for anti-HER2 therapy. Accurate assessment of the HER2 status is essential for identifying patients which will benefit from HER2 targeted therapy. HER2 status in the UK is established using a two tier strategy with IHC as the initial test and subsequent reflex of equivocal results to in situ hybridization (ISH). IHC staining of the HER2 protein is graded as 0- 3+ dependent upon the intensity of staining, cellular localisation and the percentage of cells positive in accordance with CAP/ASCO and UK guidelines. HER2 3+ cases are considered as positive, with HER2 2+ cases (equivocal) retested by ISH to ascertain the gene amplification status. Cases that are scored as 0 and 1+ by IHC have no additional testing and are classed as negative. The literature indicates that a subset of these IHC negative cases show HER2 gene amplification by FISH (range 1.1-10.7%). The aim of this audit is to evaluate the discordance rate of HER2 IHC negative, FISH positive breast cancer in the UK, with a secondary objective to resolve if this is related to the choice of antibody used. Materials and methods: This audit selected a total of 1000 sequential cases reported as HER2 negative on IHC, from three UK reference centres receiving cases from 29 different hospitals. The cases were given a unique identifying number and annonymised. Each of the three centres used a different IHC method for frontline HER2 testing with centre one using HercepTest™ (DAKO), centre two Pathway 4B5 (Roche), and centre three, Oracle (Leica Microsystems). HER2 gene amplification status was determined using dual colour FISH analysis, PathVysion (ABBOTT) fluorescence ISH (FISH) in a single centre to provide standardised methodology and assessment. HER2 was classed as amplified when the HER2/cep 17 ratio was two or greater in accordance with UK guidelines. All cases which showed discordance between IHC and FISH were retested with each of the HER2 IHC platforms to discover whether these are truly discordant results or if the discrepancy is a consequence of the choice of antibody.
Results: An interim analysis of 170 cases shows an overall IHC negative/FISH positive discordance rate of 2.37%. The discordance rate per antibody was 1.7% for HercepTest, 3.3% with 4B5 and 2.5% with Oracle. Of the FISH positive cases the HER2/cep 17 ratios ranged from 2.2 - 6.17. The overall discordance rate between IHC negative and FISH positive is in keeping with the literature and is comparable between the three IHC platforms.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-10-21.
Abstract P3-10-29: Health-Related Quality of Life (HRQoL) as Prognostic Factor for Time to Progression (TTP) and Survival in Women with Metastatic Breast Cancer
Authors: Svensson H , Einbeigi Z , Johansson H , Hatschek T , Brandberg Y 
Published: April 2011

Abstract
Background: Prognostic factors provide important information for women with breast cancer and they are used for information on the prognosis and choice of treatment. In early breast cancer, stage, malignancy grade and hormone receptor status are used regularly as prognostic factors, while age, performance status, sites of metastasis and disease-free interval (DFI) influence the outcome in metastatic disease.
The aim of the present paper was to investigate the role of HRQoL (physical, role, emotional, cognitive, and social functioning, global quality of life, fatigue and pain) at randomization as independent prognostic factors to predict time to progression (TTP) and survival. Material and methods: In the TEX trial, 287 patients with documented locally advanced or distant metastatic breast cancer were randomized to either ET (epirubicin and paclitaxel) or TEX (epirubicin, paclitaxel and capecitabine). Treatment was repeated every 3 weeks. The EORTC QLQ-C30 questionnaire was used to assess baseline HRQoL data before randomization into the trial. Data on TTP and survival were collected from the study database.
Results
A total of 252 (88%) of the patients recruited within the trial completed questionnaires before randomization. A multivariate analysis shows that the HRQoL variables fatigue, pain and role functioning was related to prolonged survival (P&lt;0. 01). Clinical variables included in the multivariate model were age, bone metastases, and treatment arm. Analyses of the relationship between HRQoL and TTP (time to progression) will be presented.
Conclusions: The present study shows that HRQoL variables, i.e. role functioning, fatigue and pain could contribute as important predictors of the outcome and may influence the choice of therapy in situations when two treatments are equally effective.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-10-29.
Abstract P3-10-33: Mammostrat® as an Immunohistochemical Multigene Assay for Prediction of Early Relapse Risk in Postmenopausal Early Breast Cancer: Preliminary Data of the TEAM Pathology Study
Authors: Bartlett JMS , Bloom KJ , Goldstein NS , van de Velde CJH , Ross DT , Seitz RS , Beck RA , Hasenburg A , Kieback D , Putter H , Markopoulos C , Dirix L , Robson T , Seynaeve C , Rea D. 
Published: April 2011

Abstract
Background: Postmenopausal early breast cancer patients, treated with endocrine therapy, have approximately 90% five year disease free survival (DFS). However, for patients at higher risk of relapse, additional adjuvant chemotherapy may be indicated. The challenge is to prospectively identify such patients. The Mammostrat test uses five immunohistochemical markers to stratify patients on tamoxifen (T) therapy into various risk groups potentially guiding treatment choices. We tested the efficacy of this panel in the TEAM trial (exemestane (E) versus T→E) to determine the relevance in patients treated with an AI.
Patients & Methods: Pathology blocks from 4598 TEAM patients were collected and tissue microarrays constructed. The cohort overall was 47% node positive, and 36% also received adjuvant chemotherapy. Samples were stained, using triplicate 0.6mm2 TMA cores, and positivity for p53, HTF9C, CEACAM5, NDRG1, SLC7A5 assessed. Each case was assigned a Mammostrat risk score and analysed for disease free survival (DFS) by marker positivity and risk score.
Results: Preliminary results on the UK TEAM cohort (1059 cases) showed 18.9% stained positive for p53 (184/972), 21.3% for NRDG1 (204/956), 26.4% for SLC7A (253/957), 21.9% for HTF9C (220/1004), 18.3% for CEACAM5 (185/1009). Complete data was available for 919 cases including patients treated with chemotherapy, with 447 (49%) designated low risk, 213 (23%) medium and 259 (28%) high risk. In univariate analysis, Mammostrat scores were prognostic (p=0.02), with 5 year DFS (see comment above) results being 86.9±1.7%, 80.1±3.0% and 80.8±2.6% for patients with low, medium and high Mammostrat scores respectively. Analyses on the entire TEAM pathology cohort are ongoing, and further data with sufficient power to evaluate the impact of Mammostrat in multivariate regression analyses will be presented. Conclusion: Preliminary analysis of the impact of the Mammostrat score in both tamoxifen and exemestane treated patients suggests it retains its prognostic value in this context. Further analysis with the power to evaluate the impact of Mammostrat in multivariate regression analyses will be presented.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-10-33.
Abstract P3-10-34: HER2 Testing by FISH: Discordance between HER2 Signals Per Cell and HER2:CEP 17 Ratio
Authors: Dintzis SM , Allison KH , Schmidt RA. 
Published: April 2011

Abstract
Background: HER2 gene amplification status may be tested by FISH using either HER2 signals per cell or HER2:CEP17 ratio. Established HER2 testing CAP/ASCO reporting guidelines allow for interpretation and reporting using either method. Both methods classify cases as amplified, not amplified or equivocal yet the two methods may yield different interpretations for the same case. We analyzed a large dataset to quantify concordance between these two testing and reporting methodologies. Materials and Methods:
We collected individual cell HER2 and CEP17 counts in 32,116 tumor cells from 1329 consecutive breast cancer cases. Data from Excel counting sheets were imported to a SQL Server database for analysis and statistics;
histograms and analyses were also performed in Excel. We specifically computed concordances between methods for HER2 signals per cell and HER2:CEP17 ratio reporting. Results:
Concordance between HER2 signals per cell and HER2:CEP17 ratio case averages was 89.8%. Most discordances involved cases classified as equivocal by either method. 7.8% of cases reported by HER2 signals per cell and 4.0% of cases reported by HER2:CEP17 ratio were classified as equivocal. 1% of cases were amplified by one method and not amplified by the other. Discussion:
This very large dataset shows that HER2 FISH reporting by established CAP/ASCO guidelines is generally concordant between the two testing methods. However, a substantial number of cases are discordant and patient treatment could vary depending on reporting criteria used. These results indicate the need for reporting by both methods to prevent missing patients who could potentially benefit from HER2 targeted therapy. Further study is necessary to determine the most clinically relevant reporting method and criteria.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-10-34.
Abstract P3-10-35: Using Automated Image Analysis To Validate Ki67 as a Clinical Prognostic Biomarker for Estrogen-Receptor Positive Breast Cancers
Authors: Magliocco AM , Kornaga EN , Klimowicz AC , Petrillo SK , Konno M , Yau A. 
Published: April 2011

Abstract
Background: Ki67, an indicator of proliferation, has been shown to be a useful prognostic and predictive marker for breast cancer. Ki67 can be used to identify two distinct estrogen-receptor positive subtypes: luminal A and luminal B. Luminal A breast cancers have been identified as having a lower proliferation and better outcome compared to luminal B. Furthermore, early clinical trials suggest that Ki67 may be useful in identifying a subset of patients that are sensitive to adjuvant docetaxel treatment. Currently, only estrogen-receptor (ER), progesterone-receptor (PR), and human epidermal growth-factor (HER2) are routinely performed. We have optimized and validated an immunohistochemical (IHC) Ki67 assay and automated computerized image analysis platform for routine clinical testing. Materials and Methods: Immunohistochemical staining was quantitatively assessed using the ACIS® III platform on a cohort (N=761) of tamoxifen treated patients who were diagnosed with breast cancer in Calgary between 1990 and 2001. Tissue microarrays were constructed using three 0.6 mm cores. Ki67 results were available for 510 patients, 461 of which are ER/PR positive and HER2 negative. Staining was performed using the DAKO FLEX ready-to-use system. The percent nuclear area positive was calculated using ACIS III and the maximum value was used in statistical analysis
Results: X-tile statistical software was used to identify an optimal Ki67 cut point to distinguish differential overall survival in node negative ER positive cancers of 18.75%. This cut point was then used to categorize the 461 ER/PR positive and HER2 negative breast cancers into luminal A (407; 88.3%) or luminal B (54; 11.7%) subtypes. The 8-year breast cancer specific survival was 85.2% (95% CI = 81.3% - 89.1%) for luminal A and 53.6% (95% CI = 39.3% - 67.9%) for luminal B (P&lt;0.0001). Cox regression showed a hazard ratio of 1.63 (95% CI = 0.99 — 2.67, p=0.055), adjusting for age, tumor size, grade and lymph node status. Discussion: Quantification of Ki67 expression using automated image analysis can be used clinically to distinguish luminal A from luminal B in ER/PR positive and HER2 negative breast cancers. The purpose of this project was to develop a reliable Ki67 assay that can be easily adopted by other testing centers. Using a ready-to-use IHC system — such as DAKO FLEX — allows for consistent results between other clinical laboratories. Additionally, using an automated, quantitative imaging system — such as the ACIS® III — reduces inter-observer variation that can occur by human visual assessment.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-10-35.
Abstract P3-11-09: Body Mass Index (BMI) and Survival: A Retrospective Review of Women with Triple Negative Breast Cancer (An Update)
Authors: Sudhindra A , Dammarich D , Ochoa R , Takita C , Mendiola MF , Hurley J , Gluck S , Welsh C , Slingerland J , Richman S , Gomez-Fernandez C , Timothee P , Diaz A , Silva OE. 
Published: April 2011

Abstract
Body Mass Index (BMI) has been reported as a risk factor for recurrence and decreased survival in women with breast cancer. At the Inter-American Breast Cancer Conference we presented data showing the effect BMI has on overall survival in women with triple negative breast cancer (TNBC). Here we present an update of this data which to our knowledge is the only study addressing the effect BMI has on outcomes in TNBC. We conducted a retrospective review of 170 patients with TNBC seen at the University of Miami Sylvester Comprehensive Cancer Center and Jackson Memorial Hospital between December of 1999 and April 2010. Charts were reviewed looking at BMI at the time of diagnosis and overall survival defined as date of last contact or date of death when known. 163 patients were included in the study. BMI was defined as normal (BMI 18.5-24.9) and overweight or obese (25 or greater). The average age at diagnosis was 50.96 years with a mean OS of 44.67 months. 21 patients (13%) had stage I disease, 61 (37.4%) had stage II disease, 81 (49.6%) had stage III disease. In patients with stage I disease 33% had a normal BMI with a mean OS of 51.7 months. 67% were overweight or obese with a mean OS of 60.2 months. In patients with stage II disease 33% had a normal BMI with a mean OS of 30.8 months. 67% were overweight or obese with a mean OS of 48.4 months. In patients with stage III disease 28% had a normal BMI with a mean OS of 37.2 months. 72% were overweight or obese with a mean OS of 43.1 months.
Survival in patients with TNBC does not appear to be negatively impacted by the patients BMI at diagnosis. While not statistically significant (p=0.274) patients with stage I TNBC that were overweight or obese tended to have an increased OS compared to those with a normal BMI. In patients with stage II disease there was a statistically significant (p=0.010) increase in OS in overweight or obese patients compared to those with a normal BMI. In the patients with stage III disease there was no significant difference in the OS (p=0.458) between patients with a normal BMI and those that were overweight or obese.
Our study shows that increased BMI at the time of diagnosis may have a positive impact on OS in patients with TNBC. Overweight and obese patients with stage I and II TNBC have an increased OS compared to those with a normal BMI. In those with stage II disease the difference was statistically significant. Although this study was limited by small sample size, if confirmed, it might suggest a relationship between obesity and survival in TNBC. Further studies are needed to evaluate these findings.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-11-09.
Abstract P3-12-06: Biomarkers of Malignant Potential in Breast Tissue in Relation to Short-Term Breast Cancer Risk
Authors: Hill D , Nibbe A , Lomo L , Royce M , Wallace AM , Bocklage T. 
Published: April 2011

Abstract
Background:
Biomarkers expressed in benign or normal breast tissue may be important indicators of subsequent risk of malignancy, but investigations identifying such have been few. Limited previous evidence suggests that loss of expression of several breast cancer tumor markers in benign tissue, relative to normal tissue, may contribute to malignant progression. We examined expression of markers implicated in tumorigenesis among women who developed breast cancer shortly after benign biopsy. Material and Methods:
We conducted a nested case-control study within a population-based cohort of 15,000 women who received benign breast biopsies between 1996 and 2005 in six New Mexico counties. We identified 95 women who developed breast cancer within 5 years of biopsy, and matched them to 3 similar controls who did not develop cancer. Benign breast as well as adjacent normal tissue was assayed using immunohistochemistry for epithelial and stromal markers plausibly related to risk of cancer development. Logistic regression models were employed to estimate odds ratios and 95% confidence intervals for breast cancer risk after adjustment for age, race/ethnicity, and risk category of benign biopsy. Results:
Women who expressed estrogen receptor alpha in their normal tissue (10% or greater staining) had a 2.9-fold increased breast cancer risk (95% confidence interval (CI) 1.0-8.3). Those who expressed Cytokeratin 5/6 (Odds ratio (OR) 3.3; 95% CI 1.2-8.8) or Her2/neu (30% or greater staining) (OR 8.2; 95% CI 0.9-70.6) in normal tissue also appeared to have an elevated breast cancer risk, relative to those with expression below the threshold. In contrast, the presence of these markers in benign tissue was unrelated to subsequent development of breast cancer. Estrogen receptor staining of 10% or greater in normal tissue, but absence of staining in benign tissue, was not a risk factor for progression to breast malignancy (OR 4.9; 95% CI 0.7-34.8) Discussion:
Our results suggest that biomarker expression in normal breast tissue may be an important component of risk assessment among women whoreceive benign breast biopsies. Findings such as these aim to identify women at highest risk for breast cancer development, allowing for the implementation of more frequent follow-up and new targeted interventions, while classifying most women as at low risk, providing reassurance and reducing the need for chemoprevention.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-12-06.
Abstract P3-12-08: Molecular Breast Cancer Subtypes in Women from Northeast China: Eight-Year Retrospective Study about Clinicopathologic Features and Survival
Authors: Nie G , Shi A-p , Song D , Yang M , Fu T , Li S-j , Han B , Zhao G , Wu D , Jia H-y , Fan Z-m. 
Published: April 2011

Abstract
Background and objectives: Analysis of gene expression has identified various molecular subtypes. These molecular subtypes defined by immunohistochemistry expression of estrogen receptor (ER) or progesterone receptor (PR) and human epidermal growth factor receptor 2 (Her2) : luminal A, luminal B, basal cell-like and HER2-expresing. This study evaluates clinical and pathologic features and survival of the four molecular subtypes in premenopausal and postmenopausal women from northeast China.
Methods: A retrospective analysis of 1214 women diagnosed with breast cancer from 2000 to 2007 in Breast Surgery Department, First Hospital of Jilin University. Four molecular breast cancer subtypes defined as: luminal A (ER+ and/or PR+, HER2-), luminal B (ER+ and/or PR+, HER2+), basal-like (ER-, PR-, HER2-), and HER2-expresing, (ER-, PR-, and HER2+). We examined the prevalence of breast cancer subtypes and analyzed the associations with patient clinicopathologic features: age, menopausal status, tumor size, lymph node status, stage of cancer at diagnosis, histological characteristics, and breast cancer-specific survival.
Results: Among the all cases, the luminal A subtype was the most prevalent in our study sample (56.0%) compared with basal -like (18.5%), luminal B (13.7%), and HER2-expresing subtypes (11.8%). The four molecular subtypes differed significantly by menopausal status (P=0.011), age (P&lt;0.001) and lymph node status (P&lt;0.001). Luminal A subtype was more likely to with Stage II breast cancer (P&lt;0.001) and most present with size of 2.1-5 cm (P&lt;0.001). The luminal B and the HER2-expresing subtypes presented an increased association with more aggressive clinical course when compared with others subtypes. The estimated median follow-up period for all subjects was 54 months (range, 1 month to 120 months). The 8-year overall survival for all patients was 81.3% (95%CI, 79.4-83.7) and disease-free survival was 77.8% (95% CI, 75.4-79.9). The Kaplan-Meier curve showed breast cancer-specific survival differed significantly among the molecular subtypes (P &lt; 0.03), with the luminal B and HER2-expresing subtypes having the poorest outcome.
Conclusion: Luminal A breast tumor appeared the better outcome than the others three subtypes and the shortest survival was HER2-expresing subtype. The poor clinical outcomes of luminal B subtype with women from northeast China were different from those of Western women could contribute to the poor prognosis of breast cancer observed in this cohort of patients and some of them couldn't accept molecular targeted therapy with trastuzumab by poor economic situations.
Figure available in online version.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-12-08.