bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preliminary Comparison between AQUA and Centralised ER/PgR Analysis within the TEAM Pathology Study.
Authors: Bartlett J. , Rimm D. , Brookes C. , Dolled-Filhart M. , Robson T. , van de Velde C. , Billingham L. , Campbell F. , Hasenburg A. , Hille E. , Kieback D. , Putter H. , Markopoulos C. , Christiansen J. , Gustavson M. , Mallon E. , Meershoek-Klein Kranenburg E. , Parideans R. , Seynaeve C. , Rea D. 
Published: December 2010

Abstract
Background: The Tamoxifen and Exemestane Adjuvant Multinational (TEAM) trial identified quantitative relationships between ER/PgR (Can Res 69:83S) and patient prognosis, and suggested that high ER expression might be predictive for benefit from aromatase inhibitors. Conventional immunohistochemical assays, even when performed centrally, appear to be more variable than fluorescent immunohistochemical assays analysed by automated image analysis such as the AQUA system. However, output from the two systems may provide subtly different results for biomarkers. We have performed analysis of ER/PgR using AQUA technology in the TEAM pathology cohort and will present data on the full anlaysis of ER/PgR by central IHC and AQUA in 4600 cases. Preliminary data on ER (using a single TMA core) are included in the current analysis.Patients & Methods: TMAs from 4598 TEAM patients were analysed by AQUA and image analysis using established algorithms performed. Comparisons between IHC and AQUA were performed and outcome data will be analysed and presented.Results: Interim AQUA results from a single core were available from 2319 TEAM cases. Analysis of results suggested incremental increases in AQUA scores across conventional Allred categories (2-8). Regression analysis suggests that multiple cores may be required adequate representation of ER expression. PgR data will be presented.Conclusion: Initial comparison between AQUA and ER expression by central IHC suggests these methods are comparable. Further data is required to assess the potential value of AQUA scores and will be presented.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3045.
Computerized Histologic Image-Based Risk Score (IbRiS) Classifier for ER+ Breast Cancer.
Authors: Ganesan S. , Madabhushi A. , Basavanhally A. , Xu J. , Bhanot G. , Barnard N. , Toppmeyer D. 
Published: December 2010

Abstract
Background: Measurement of estrogen receptor (ER) expression is a routine part of clinical evaluation of individual breast cancers and is used to guide treatment. However not all ER+ breast cancers show equal benefit from hormonal or other treatment. The RT-PCR based Oncotype Dx assay, has been recently shown to robustly stratify early stage ER+ breast cancer and identify those tumors that will have low recurrence rates when treated with adjuvant hormonal therapy alone. Interestingly, standard pathologic grading, based on visual analysis of tumor morphology by trained pathologists, has a strong correlation with Oncotype Dx recurrence scores; low recurrence tumors are mostly low grade, and high recurrence tumors are mostly high grade. However, a major problem with use of pathologist-assigned histologic grade as a prognostic tool is the lack of reproducibility of histological grading between different pathologists. Computer aided image analysis and machine learning techniques offer a way to obtain highly reproducible image-based classification of ER+ breast cancer. These analyses can be performed on digital images of routinely obtained breast cancer histology and be incorporated into a prognostic assay.Materials and Methods: High resolution digital images were obtained for a series of ER+ breast cancers for which associated Oncotype Dx Assay results were available. Regions of invasive breast cancer were identified and then processed by computer-assisted image analysis methods. An automated nuclear detection scheme based on Expectation Maximization algorithm was used to identify cancer cell nuclei, followed by graph-based feature extraction using the Voronoi graph, Delaunay Triangulation and Minimum Spanning Trees, and dimensionality reduction using Graph Embedding with Support Vector Machine based classification. The final manifold generated by GE was unwrapped into a linear space and a Euclidean distance metric was used to generate a single score (Image Based Risk Score- (IbRiS)) for each sample. Correlations between IbRS, clinical features such as grade, and Oncotype Dx Recurrance Score were determined.Results: Unsupervised analysis of image-based features of high resolution digital images of ER+ breast cancer histology leads to natural separation of tumors, with low grade tumors separating from high grade tumors. There is also a robust separation of tumors with high Oncotype Dx Recurrance Scores from tumors with low Recurrance Scores.Discussion: Unsupervised analysis of high resolution image-based features can stratify ER+ breast cancers in a fashion that correlates well with a gene-expression based prognostic assay, Oncotype Dx. These data suggest that tumors with distinct gene-expression profiles also have distinct image-based features that can be measured by computer-aided image analysis and used to build prognostic and predictive assays.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3046.
Tumor-Stroma Ratio within the Primary Tumor Is a Prognostic Factor in Early Breast Cancer Patients, Especially in Triple-Negative-Carcinoma Patients.
Authors: de Kruijf E. , van Nes J. , van de Velde C. , Putter H. , Smit V. , Liefers G. , Kuppen P. , Tollenaar R. , Mesker W. 
Published: December 2010

Abstract
Background: Breast cancer patients comprise a prognostic heterogeneous group. Stroma-tissue surrounding cancer cells plays an important role in tumor behavior. The prognostic value of the tumor-stroma ratio was evaluated.Material and Methods: A cohort of 574 patients with early breast cancer, primarily treated by surgery between 1985 and 1994 was analyzed. The percentage of intra-tumoral stroma was visually estimated on haematoxylin-eosin-stained histological sections from primary tumor tissue by two observers. Patients with more than 50% intra-tumor stroma were quantified as stroma-rich and patients with less than 50% intra-tumor stroma as stroma-poor.Results: Of all tumors, 68% were classified as stroma-rich and 32% as stroma-poor. Cohen's kappa coefficient revealed an almost perfect agreement in classification (kappa=0.85; 94% concordance in classification) between the two observers. For the total group of patients, stroma-rich tumors had a shorter relapse free period (RFP) (Hazard ratio (HR) 1.62; 95%CI 1.23-2.13; p=0.001) and overall survival (OS) (HR1.29; 95%CI 1.03-1.60; p=0.025) compared to stroma-poor tumors. Tumor-stroma ratio was an independent prognostic parameter for all patients (p&lt;0.001) and in stratified analysis for patients that received systemic treatment. Importantly, within the triple-negative-cancer (TNC) subpopulation, patients with stroma-rich tumors had a 3.19 times higher risk of relapse (p=0.003) compared to patients with stroma-poor tumors, independently of grade and lymph node status. Five year RFP-rates for patients with stroma-rich compared to stroma-poor tumors were 56% and 81% respectively.Discussion: Tumor-stroma ratio was an independent prognostic factor for RFP in breast cancer patients, especially in TNC. The tumor-stroma ratio is easy to apply, of low cost and reproducible. It is a candidate parameter that can easily be implemented in routine daily diagnostics to optimize risk-stratification for breast cancer patients and should therefore be considered to be implemented in standard pathology reports.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3049.
Feasibility of Sentinel Lymph Node Biopsy in Multiple Unilateral Synchronous Breast Cancer: Results of a French Prospective Multi-Institutional Study (IGASSU 0502).
Authors: Giard S. , Penel N. , Chauvet M. , Mignotte H. , Martel P. , Tunon de Lara C. , Gimbergues P. , Dessogne P. , Classe J. , Fondrinier E. , Marmousez T. , Blanchot J. 
Published: December 2010

Abstract
Introduction: Controversy remains over whether to perform sentinel lymph node biopsy (SLNB) in multiple (multicentric or multifocal) unilateral synchronous breast cancer. Several small retro- or prospective studies, included pre- or post-operative (or both) multiple synchronous tumours (MST) have suggested that the test performance of SLNB is similar to that seen in unifocal disease. The purpose of this study was to evaluate the feasibility and accuracy of SLNB in preoperatively diagnosed invasive MST.Patients and Methods: The Interest of Axillary SLNB in Multiple Invasive Breast Cancer (IGASSU) study was a prospective multi-institutional study with initial breast surgery, SLNB, and systematic level I to II axillary lymph node dissection (ALND). Patients eligible for the IGASSU study had an operable invasive MST, defined as two or more physically separate invasive tumours in the same or different breast quadrant. The diagnosis of invasive MST was confirmed histologically in all patients by core needle biopsy before surgery. Detection of sentinel node was performed by using either blue patent or radiocolloide injection or both. Injection sites were subareolar.Statistical Analysis: Sensitivity (Se), negative predictive value (NPV), accuracy (A), false negative rate (FNR) and their 95%-confidence intervals (95%CI) were calculated with a classical 2x2 contingency table. A univariate analysis using odds ratio calculation was performed to identify the risk factors for false negative results.Results: Between March 1, 2006, and August 31, 2007, 216 patients were prospectively included from 16 institutions. Of these patients, 211 were evaluable. The SLNB identified rate were 93.4% (197/211). A mean number of 2.2 SLN (range, 1 to 8, ± 1.4) was successfully excised. The mean number of resected nodes in ALND was 12 (range, 1 to 39, ± 5.7). The FNR was 13.6% (14/103) [95%CI: 7- 20%], Se was 86 .4% (89/103) [95%CI: 79- 93%], NPV was 87% (94/108) [95%CI: 80-93%], A was 92.9% (183/197) [95%CI: 89- 96%]. For the 14 false-negative SN, all had ≤ 3 involved nodes in ALND. Table 1 shows patterns of management of the axilla.Table 1 ALND+ALND-Non-identified SLNB113Identified SLNB+4544Identified SLNB-1494 In a univariate analysis, tumour location (only external location vs other location) was the only clinico-pathological factor influencing the FNR (22% [11-33%] vs 7% [4-10%]), even then median aggregate histological tumour size was smaller in external tumours (17mm [range, 12-80] vs 34mm [range, 8- 90], p=0.016).Conclusion: With a FNR of 13.6% (95%CI: 7-20%), we do not recommend SLNB as a routine procedure for multiple unilateral synchronous breast cancer, even for small tumour foci.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 305.
The Influence of Mode of Presentation on the Pattern of Recurrence in Early Breast Cancer (EBC).
Authors: Mansell J. , Angerson W. , Wilson C. , Doughty J. 
Published: December 2010

Abstract
IntroductionAn early peak in recurrence exists in women with EBC. This may be explained underlying tumour biology or a reaction to surgery. Screen detection has been shown to have a prognostic effect independent of disease stage suggesting a connection with underlying tumour biology. We aim to determine if the pattern of recurrence differs between modes of presentation.MethodsData from 3 centres in Glasgow of consecutive women aged between 50-65yrs with early stage breast cancer (EBC) diagnosed between 1995 and 2001 were examined. Recurrence was defined as invasive disease at any site. Patients were grouped by mode of presentation into screen detection and symptomatic. Kaplan Meier and time dependent Cox analysis were performed.Results1534 women were included with a median follow up of 5.5yrs. Mode of presentation was screening in 1007 (65.6%) women. At 2.5yrs cumulative recurrence was 2.5% (95% CI 1.5-3.5) in the screen detected group and 9.7% (7.2-12.2) in the symptomatic group. At five years the corresponding rates were 7.8% (6.0-9.6) vs. 19.1% (15.6-22.6). Time dependent multivariate analysis showed that the difference in the risk of recurrence between the modes of presentation was significantly different within 2.5yrs from diagnosis compared with later than 2.5yrs (p = 0.019). The hazard ratio for recurrence within 2.5 yrs was 0.59 (95% CI 0.34-1.00, p=0.05) and after 2.5yrs was 1.23 (0.84-1.80, p =0.285).ConclusionsThese results suggest that women with screen detected cancers have a better prognosis initially following diagnosis independent of disease stage. However this additional benefit isn't maintained with longer follow up.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3056.
Incidence and Demographic and Tumor Characteristics of HER2-Positive Invasive Breast Cancer in a Large, Unselected Population, 2000-2006.
Authors: Fehrenbacher L. , Habel L. , Capra A. , Anthony A. , Li X. , Quesenberry C. , Fulton R. 
Published: December 2010

Abstract
BACKGROUND: Most HER2 data have been generated from populations of invasive breast cancer (IBC) patients with selected patient and tumor characteristics (clinical trials, referral centers). The average age of women in US adjuvant trastuzumab trials was 49. Pre 2000, clinical trials of adjuvant chemotherapy included 25-40% HER2+ cases. We used an unselected population of women with IBC to estimate the age-specific incidence rates of HER2+ IBC and compare patient and tumor characteristics of HER2+ and HER2- disease.METHODS: Among female members of Kaiser Permanente Northern California (KPNC) 20 years or older (n=1.22 million), we identified all those diagnosed with a new primary IBC in 2000-2006 (n=16,975). During this period, all IBCs were routinely tested for HER2 by KPNC's regional IHC laboratory (center of excellence for HercepTest, CLIA licensed and CAP certified) and those that were IHC 2+ were sent for FISH testing; IHC 3+ or IHC 2+/FISH+ (ratio ≥ 2.0) were considered HER2+. Demographic and tumor characteristics were derived from the KPNC tumor registry. *Complete HER2 testing available for 94% of IBCs.RESULTS: Incidence of HER2+ IBC increased less dramatically with age and peaked 20 years earlier than incidence of all IBC (Table 1). Among those with IBC, the percent that were HER2+ decreased with age. Of all HER2+ IBCs, 69% were ≥50 years old and 42% were ≥60 years old.Incidence of all IBC and incidence of HER2+ diseaseAge GroupPerson-YrsNo. of IBCsIBC rate/100KHER2+ IBCs*%HER2+HER2+IBC rate/100K20-39288153371024.6416424.75.6940-4917402132680154.0049819.728.6250-5915535284354280.2759914.538.5660-699677624280442.2649412.351.0570-796676013318497.002718.740.5980+3666531633445.381429.638.73ALL817729016975207.59216813.626.51 The percent of tumors that were HER2+ increased with stage (local=11%, regional=18%, distant =25%), tumor differentiation (well =2%, moderate =12%, poor=26%, undifferentiated=30%), and generally with size (&lt;0.5cm=17%, 0.5-0.9cm=7%, 1-1.9 cm=10%, 2-4.9 cm=17%, &gt;5 cm=20%). ER- and PR- tumors were more likely to be HER2+ (of all ER- tumors, 29% were HER2+; of all PR- tumors, 25% were HER2+; of all ER+ tumors, 10% were HER2+; of all PR+ tumors, 9% were HER2+). Among all IBC patients, percent of disease that was HER2+ was highest for Asians (20%) and lowest for Caucasians (12%).CONCLUSION: In a large, unselected, population of invasive breast cancer patients, the incidence of HER2+ disease was highest among women aged 60-69 years. Among breast cancer patients, HER2+ disease was highest in Asians. The percent HER2+ was 13.6% for all breast cancer patients in this population based cohort and highest (24.7%) in the 20-39 year age group.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3058.
The TGFBR1*6A/9A Polymorphism Is Not Associated with Differential Risk of Breast Cancer.
Authors: McInerney N. , McInerney N. , Colleran G. , Rowan A. , Barclay E. , Jones A. , Curran C. , Miller N. , Tomlinson I. , Sawyer E. , Sawyer E. , Kerin M. 
Published: December 2010

Abstract
Background: A polymorphic 9-bp deletion in exon 1 of TGFBR1 (TGFBR1*6A) has been identified as a low-penetrance cancer susceptibility allele. The strongest association in the initial studies was with breast cancer; however these studies included patients with different types of cancer, including colon, cervical and breast carcinomas, with only a small proportion being breast cancer patients. In subsequent case-control studies focussing on breast cancer alone, the results have been equivocal. Methods: In order to clarify whether TGFBR1*6A is associated with breast cancer risk, we have genotyped this polymorphism in 988 breast cancer cases and 1016 controls form the West of Ireland and also performed a meta-analysis of previously published data (5150 cases and 6344 controls). All statistical analyses were undertaken using STATA 9.2.Results: In our series from the West of Ireland, we found no association (genotypic odds ratio (OR) under a dominant model= 0.93, 95% confidence interval (CI) 0.73-1.19, p=0.57; allelic OR=0.93, 95% CI 0.74-1.15, p=0.49). Meta-analysis showed evidence of heterogeneity among studies. Using the random effects model, there was no evidence of an association of the *6A allele with breast cancer (genotypic OR under a dominant model= 1.10, 95% CI = 0.94 to 1.28, p=0.24, allelic OR=1.12, 95%CI 0.97-1.31, p=0.13) with breast cancer. Conclusions: This study confirms that TGFBR1*6A is not associated with breast cancer and highlights the problems associated with small case-control studies, especially where minor allele frequencies are low. It remains to be seen whether the association with other cancer types, including colorectal cancer, can be validated in large case-control series.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3062.
In Asian-American Women, Westernization Influences Estrogen Metabolism, but Not Total Endogenous Estrogen Production.
Authors: Ziegler R. , Fuhrman B. , Xu X. , Gail M. , Keefer L. , Veenstra T. , Hoover R. 
Published: December 2010

Abstract
Background: Historically, breast cancer incidence rates were 4-7 times higher in the United States than in China and Japan. When Asian women migrate to the U.S., their risk rises over several generations and approaches that in U.S. Whites. Endogenous estrogen has been postulated to explain these international differences. Methods: In a population-based case-control study in Chinese, Japanese, and Filipino women living in San Francisco-Oakland, CA; Los Angeles, CA; or Oahu, HI, we documented a six-fold gradient in breast cancer risk with Westernization. Using 12-h, overnight urines from 263 premenopausal mid-luteal and 168 postmenopausal control subjects, we investigated associations of estrogens and estrogen metabolites (EM) with Westernization, particularly birthplace in the East or West. Fifteen EM were measured concurrently by liquid chromatography-tandem mass spectrometry with high accuracy, precision, and sensitivity. Log-transformed EM measures, adjusted for age and ethnicity, were compared by robust linear regression. Results: Total urinary EM (pmol/mg creatinine) was not associated with birthplace in premenopausal or postmenopausal women. When the three estrogen hydroxylation pathways were expressed as percent of total EM, the relative difference by birthplace, West compared to East, was 15% lower for 2-pathway EM (p=0.009), 7% lower for 4-pathway EM (p=0.37), and 10% higher for 16-pathway EM (p=0.008). Similar results were observed for individual EM in each pathway, premenopausal and postmenopausal women, and the three ethnicities. In both menopausal groups, 2-pathway EM concentration decreased steadily with increasing risk across six categories of Westernization. Conclusions: Our results do not indicate that total estrogen production explains the increased breast cancer risk in Western societies. However, estrogen metabolism patterns, especially reduced 2-hydroxylation, may contribute to the elevated risk; and underlying mechanisms merit further exploration.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3063.
Prevalence of Methylenetetrahydrofolate Reductase C677T and A1298C Polymorphisms and Risk of Breast Cancer in Mexican Women: An Interim Report of a Case-Control Study.
Authors: Scott S. , Loyo T. , Borbolla J. , Villela L. , Perfecto Y. , Cardona S. 
Published: December 2010

Abstract
Background: Among other causes, Breast Cancer (BC) appears as a result of genetic and epigenetic changes. Modifications in important pathways, such as the reactions that provide essential cofactors for synthesis of S-adenosylmethionine (one-carbon metabolism), and those involved in DNA synthesis and methylation could be linked to the development of this disease. Research has been conducted about whether MTHFR polymorphisms are related to the development of breast cancer in at least 10 different races, with different outcomes. Two of the most frequently studied MTHFR polymorphisms are C677T and A1298C, and their frequency is unknown among Mexican women. Our objective was to determine the frequency of these two polymorphisms and to ascertain weather their presence increases the risk of developing BC in our population.Materials and methods: 37 blood samples from histopatologically confirmed breast cancer patients were collected from hospitals in Monterrey, Uruapan and Villahermosa, all in Mexico. 115 healthy control samples were obtained from the same cities, and were matched for age in 5-year interval-groups. Cases and controls were third generation Mexican and older than 18 years. Genotyping of every sample was performed by PCR and restriction with enzymes.Results: The C677T Polymorphism was found in 28 cases (75.67%), whereas 76/115 controls (66.08%) showed the polymorphic allele. Case-controls analysis was adjusted to the confounding variable age group, an odds ratio of 1.58 (IC 95% de 0.66 – 3.82) was obtained. We did not find a significant relationship between the presence of the C677T polymorphism and the presence of breast cancer. The A1298C Polymorphism was found in 19/37 cases (51.35%), while only 32/115 (27.82%) of the control samples contained the allele. The odds ratio adjusted for the same confounding variable was 2.72 (IC 95%: 1.26 – 5.87). These results suggest a significant association between the presence of the polymorphism and BC.Discussion: Despite the exhaustive research that has been conducted regarding MTHFR polymorphisms C677T and A1298C, their association to the risk of breast cancer remains unclear. Some research groups even suggest that the presence of the polymorphisms, either individually or combined, confers certain protection against the disease. Up until now there were no data in Mexican population. Differences in the results of different works probably lie in the nature of the populations analyzed and the experimental design. We believe that a bigger sample size will allow us to determine if A1298C polymorphism is indeed, a risk factor for BC in Mexican women.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3064.