bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P3-10-01: Quantitative Gene Expression Analysis in a Large Cohort of Estrogen-Receptor Positive Breast Cancers: Characterization of the Tumor Profiles in Younger Patients (≥40 yrs) and in Older Patients (≥70 yrs)
Authors: Shak S , Baehner FL , Stein M , Chen I , Yoshizawa C , Watson D , Swain SM. 
Published: April 2011

Abstract
Background: Previous studies have identified differences in the presentation, biology, and behavior of breast cancer as a function of patient age. To directly study breast cancer tumor profiles as a function of patient age, we examined the Oncotype DX Recurrence Score (RS) and the expression of ER, PR, and proliferation-related genes in a large cohort of invasive breast cancers.
Material and Methods: All tumor specimens successfully examined in the Genomic Health laboratory from June 2004 through March 2010 were included. Standard RS testing was performed. Quantitative expression for ER, PR, HER2, and the five proliferation genes, CCNB1, Ki-67, MYBL2, STK15, and Survivin, was measured by quantitative RT-PCR on a scale from 2 to 15 (relative to reference genes), where a one unit increment is associated with an approximate 2-fold increase in expression. The proliferation index (PI), a component of the RS, was calculated as the average of the expression of the five proliferation genes. ER negative tumors (ER&lt;6.5) were excluded. Means and medians were calculated; with this very large sample size, all comparisons between groups were statistically significant (P&lt;0.05).
Results: Among the 145,236 breast cancers, 5,794 (4.0%) were ≥40 yrs, 117,740 (81.1%) were 41 — 69 yrs, and 21,702 (14.9%) were ≥70 yrs. A wide range of RS (0 to &gt;80) was observed in all age groups. The mean RS, median RS, and proportion of patients in each of the standard RS groups are shown in the Table. The average RS is slightly higher in the younger age group and lower in the older age group. Similarly, the proportion of high RS tumors is higher in the younger age group and lower in the older age group. However, many young patients are in the low RS group and many older patients are in the high RS group. Small differences in the mean expression of quantitative ER, quantitative PR, and the Proliferation Index were observed. Younger patients had lower mean ER, higher mean PR and higher proliferation.
Discussion: Among estrogen receptor positive breast cancers, the average RS is slightly higher in younger patients and is slightly lower in older patients. However, it is notable that a wide range of RS was observed in all age groups; many young patients are in the low RS group and many older patients are in the high RS group. These results demonstrate the importance of standardized quantitative measurement of gene expression on a continuous scale, and suggest that, for ER positive breast cancer, age per se does not predict individual tumor biology.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-10-01.
Abstract P3-10-16: Quantitative Subtractive Immunofluorescence To Develop a Surrogate for Mena Inv(asive) Isoform Is Associated with Poor Outcome in Breast Cancer
Authors: Agarwal S , Jones JG , Oktay M , Balsamo M , Condeelis J , Gertler F , Rimm DL 
Published: April 2011

Abstract
Introduction:
Previous work has shown that the inv isoform of Mena, an actin binding protein, is associated with invasion at the cellular level and metastasis in the context of the microenvironment in both animal models and humans (Robinson, B.D. et al. Clin Cancer Res 15, 2433-2441 (2009). However, the prognostic value for metastasis of MenaINV itself is unknown because there is no antibody that directly recognizes this isoform. Here we describe a method to assess a surrogate for MenaINV by measuring total Mena and subtracting the levels of the 11a (non-invasive) isoform. Method: Total Mena and Mena11a were measured in two independent retrospective breast cancer cohorts with 20 year follow-up using tissue microarray and quantitative immunofluorescence (AQUA) technology in a previously described multiplexed mode. AQUA scores for each marker were converted into z scores followed by subtraction of Mena 11a (noninvasive form of Mena) from total Mena (invasive and non-invasive) = Mena(inv) surrogate. This was calculated for each patient and correlated with clinical and pathological characteristics as well as disease-free survival in both cohorts.
Results: In the older Yale cohort, Kaplan Meier analysis dividing the Mena(inv) surrogate by quartiles suggested collapse of the top three quartiles followed by comparison to the fourth quartile (log rank p= 0.0003, n=501). The 4th quartile was also significant in node positive (log rank p=0.0047, n=267) and estrogen negative (ER) patient subgroups (log rank p=0.0003, n=234). Cox multivariate analysis showed Mena(inv) was independent of age, tumor size, nuclear grade, nodal status, ER, PR, Her2 (HR=0.636, 95% CI=0.47-0.86, p=0.0038, n=420). The newer Yale cohort showed similar results, but that cohort also had data on local vs. distant recurrence. The relative risk of distant recurrence in this cohort is 2.56 (p=0.011) for patients with high Mena (inv) compared to 1.96 (p=0.055) for any recurrence.
Conclusions: High Mena (inv) surrogate shows prognostic value for poor survival in two independent breast cancer cohorts with some suggestion of preferential prognostic value for distant recurrence.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-10-16.
Abstract P3-10-18: Early Detection of Recurrent Breast Cancer Using Metabolite Profiling
Authors: Asiago VM , Alverado LZ , Shanaiah N , Gowda NG , Owusu-Sarfo K , Ballas R , Raftery D 
Published: April 2011

Abstract
Background: The growing field of metabolite profiling (or metabolomics) focuses on the quantitative detection of multiple small molecules in biological systems that result from pathophysiological stimuli. As is the case for early detection of primary breast cancer, it is anticipated that early diagnosis of breast cancer recurrence will not only improve survival but also help clinicians determine the best therapeutic strategies for patients by avoiding under or over treatment. We report on the development of an early test for recurrent breast cancer using metabolite profiling methods. Methods: We applied a combination of nuclear magnetic resonance (NMR) and gas chromatography-mass spectrometry (2D GC-MS) to analyze the metabolite profiles of 257 serial serum samples from breast cancer patients consisting 116 samples from breast cancer recurrence and 141 samples from breast cancer patients with no evidence of disease (NED). NMR and GC-MS data were analyzed by combining advanced univariate and multivariate statistical methods and comparison of individual spectral features between patients with and without recurrent breast cancer. Results: From multivariate analysis of hundreds of spectral features, ten metabolite markers (7 from NMR and 3 from GC-MS) were targeted to build logistic regression model, which yielded a prediction model with a high accuracy (AUROC &gt;0.89 using 5 fold cross validation) with a sensitivity of 86% and specificity of 89%. When the model was tested using leave one patient cross validation it yielded a sensitivity of 75% and a specificity of 83% (AUROC &gt;0.88). In addition, strikingly, over 55% of the patients could be correctly predicted to have recurrence as early as 13 months before the recurrence was actually diagnosed clinically, representing a large improvement over the current diagnostic assay CA 27.29. A second statistical approach using independent training and testing sets yielded very similar results. To the best of our knowledge, this is the first study to develop and validate a prediction model for early detection of recurrent breast cancer based on the metabolic profiling. The combination of complementary NMR and MS analytical methodologies is particularly useful for building accurate profiles. Conclusion: Metabolite profiling methods provide a powerful approach for the development of diagnostic tests for monitoring breast cancer patients.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-10-18.
Abstract P3-10-19: Breast Cancer Risk Prediction Model in Korean Women Using Five Polymorphisms Identified in Genome Wide Association Studies
Authors: Han W , Woo JH , Yu J-H , Ahn SK , Kim HS , Shin HC , Yom CK , Moon H-G , Noh D-Y 
Published: April 2011

Abstract
Background: Recently indentified genetic variants from genome-wide association studies of breast cancer have not been validated in Asian population except for Chinese. We sought to confirm the association in ethnically distinct Korean women and to make genetic risk assessment model using multi-gene markers
Materials and Methods: 3321 invasive breast cancer patients operated in Seoul National University Hospital and 3500 healthy control women from a population based cohort were genotyped for 5 single nucleotide polymorphisms (SNPs) using Taqman assay. The SNPs genotyped were rs2046210 (6q25.1), rs4973768 (3p), rs2981582 (FGFR2), rs3803662 (TNRC9), and rs889312 (MAP3K1).
Results: The five SNPs were significantly associated with the risk of breast cancer in dominant, recessive, and co-dominant model (p-values from 0.012 to 3.41E-08). Minor allele frequencies were between 0.2 and 0.5. Odds ratios were between 1.14 and 1.51. Multi-gene logistic regression risk model was made with this 5 SNPs. Women who have all protective variants showed odds ratio of 0.43, while women who are homozygous for risk variants in all 5 SNPs showed odds ratio of 2.36 compared with women with the most common genotype.
Conclusion: We found that 5 SNPs from GWAS in mostly women of European ancestry were also significantly associated with breast cancer risk in Korean women. The multi-gene risk assessment model might be useful to classify women into relevant risk groups.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-10-19.
Abstract P3-10-22: Prognostic Significance of Aurora Kinase A Expression in Three Cohorts of Node-Negative Breast Cancer Patients
Authors: Schmidt M , Petry IB , Boehm D , Gebhard S , Lebrecht A , Koelbl H , Gehrmann M , Hengstler JG 
Published: April 2011

Abstract
Background: Aurora kinase A (AURKA) is important for cell cycle progression. Inhibitors that target AURKA are currently in clinical development. We examined the prognostic impact of AURKA in three cohorts of node-negative breast cancer patients without adjuvant systemic therapy (n=766).
Methods: AURKA (probe set ID 204092_s_at) was analysed utilizing microarray based gene-expression data of three independent and previously published cohorts of node-negative breast cancer patients (Mainz, Rotterdam, TRANSBIG). In addition to AURKA, we examined the prognostic impact of age, histological grade, tumor size, estrogen receptor (ER) and HER2. Metastasis-free survival (MFS) was analyzed with univariate and multivariate Cox regression.
Results: AURKA displayed a strong positive correlation with grade (P&lt;0.001), tumor size (P&lt;0.001), HER2 (P&lt;0.001), and a negative correlation with ER (P&lt;0.001), respectively. Patients with higher expression of IGKC showed shorter MFS in the Mainz cohort (HR 1.629, 95% CI 1.243-2.134, P&lt;0.001), Rotterdam cohort (HR 1.567, 95% CI 1.271-1.933, P&lt;0.001), and TRANSBIG cohort (HR 1.331, 95% CI 1.081-1.640, p=0.007), respectively. Accordingly, AURKA was significant in univariate analysis in the whole cohort of patients (HR 1.523, 95% CI 1.343-1.726, P&lt;0.001). Using multivariate Cox regression, only tumor size retained its independent prognostic significance (HR 1.818, 95% CI 1.196-2.765, p=0.005). AURKA (HR 1.221, 95% CI 0.987-1.511, p=0.065) and histological grade (HR 1.551, 95% CI 0.955-2.520, p=0.076) showed only borderline significance for MFS.
Conclusion: AURKA has prognostic relevance in three independent cohorts of node-negative breast cancer patients making it a suitable target for therapy with Aurora kinase inhibitors.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-10-22.
Abstract P3-10-27: Caspase Variant as Prognostic Marker in Patients with Early Breast Cancer
Authors: Chae YS , Lee SJ , Jung JH , Park HY , Lee S-W , Kim WW , Lee SJ , Kang BW 
Published: April 2011

Abstract
Background: Since apoptosis induced by caspases may play a role in the prognosis of breast cancer, the present study analyzed the polymorphisms of caspase genes and their impact on the survival of 240 patients with early invasive ductal breast cancer.
Material and Methods: The genomic DNA was extracted from paraffin-embedded tumor-free tissue or blood, and 8 single nucleotide polymorphisms (SNPs) of 5 apoptosis-related genes in the apoptosis pathway determined using a Sequenom MassARRAY system. Results: During the median follow-up of 68.6 (range, 36.3-173.1) months, 43 relapses and 25 deaths occurred. Among the target polymorphisms, the caspase 9 gene polymorphism (CASP9 rs4645978) in a dominant model of the A allele was associated with survival in a log-rank test (P &lt; 0.05). In a multivariate analysis, the GA+AA genotype of CASP9 rs4645978 was significantly correlated with a better disease-free survival (HR = 0.250; 95% CI = 0.075 - 0.840; P = 0.025), while marginally with distant disease-free or overall survival (HR = 0.360 and 0.337; P = 0.118 and 0.158, respectively). No clinicopathologic difference was observed according to the genotypes of this polymorphism. Discussion: The CASP9 rs4645978 was identified as a possible prognostic factor of survival in patients with operated invasive breast cancer.
Figures available in online version.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-10-27.
Abstract P3-10-28: Breast Cancer Patients with Neoadjuvant Chemotherapy Have a Different Clinical Significance of the Ki-67 Expression before and after the Treatment
Authors: Wada N , Asaga S , Yamauchi C , Fujii S 
Published: April 2011

Abstract
Background: Reliable predictive and prognostic markers for routine diagnostic purposes are needed for breast cancer patients treated with neoadjuvant chemotherapy (NAC). Ki-67 is a marker for proliferating cells and is overexpressed in many breast cancers. Aim of this analysis was to evaluate the potential role of Ki-67 as a biomarker for the breast cancer patients with NAC.
Patients and Methods: A retrospective search of a prospectively maintained clinical breast cancer database was performed to identify patients treated with NAC at the National Cancer Center Hospital East. The expression of Ki-67 was assessed using immunohistochemistry (MIB-1) in pretherapy core-needle biopsy and post-therapy surgical excision specimens. Levels of Ki-67 index (percentage of Ki-67 positive cancer nuclei) were dichotomized as high (over 10%) and low (less or equal 10%). Survival curve was calculated using Kaplan-Meier method. Log-Rank test was used to detect differences.
Results: Records were available for 296 patients who were received NAC (anthracycline and/or taxane based) between Nov 2001 and Nov 2009. High and low Ki-67 index in pre-therapy were 173 and 123 cases, respectively. 51 cases (17%) of all achieved a pathological complete response (pCR: no residual invasive disease in the breast). pCR rate (23%) in high Ki-67 was significantly different from that (9%) in low Ki-67. 5-year overall survival estimates were 69% and 75%, respectively. However, there was not difference between the groups in overall survival curve at a median follow-up time of 31 months. Of 245 cases with residual invasive, high and low Ki-67 index in post-therapy were 80 and 165 cases, respectively. 62 cases maintained high Ki-67 index before and after NAC, 94 cases maintained low Ki-67 index. There was significantly difference between high and low Ki-67 indexes of post-therapy in overall survival curve (P&lt;0.01), 5-year overall survival estimates were 51% and 81%, respectively. Moreover, there was not significant different between 51 cases with pCR and low Ki-67 index in overall survival curve.
Conclusions: Although Ki-67 index in pre-therapy is a useful predictor for the therapeutic response to NAC, high Ki-67 index in pre-therapy dose not imply that the patients have a worse prognosis. Ki-67 index in post-therapy is useful to predict outcomes for patients with residual invasive disease.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-10-28.
Abstract P3-10-40: Expression and Prognostic Significance of Cancer Testis Antigens (CTA) in Primary Breast Cancer: Possible Diagnostic Markers and Therapeutical Targets
Authors: Balafoutas D , zur Hausen A , Jungbluth A , Denschlag D , Jäger M , Gitsch G , Stickeler E. 
Published: April 2011

Abstract
Backround: Cancer Testis Antigens (CTA) are a family of proteins normally expressed in the human germ cells such as in the testis. They also have been found in various types of malignant tumors including breast cancer. Because of their restricted expression pattern they are frequently able to elicit T-cell immune responses, and therefore they are considered as ideal targets for cancer immunotherapy. Breast differentiation antigen NY-BR-1 has also immunogenic properties. The aim of this study was to explore the CTA expression in breast cancer and detect possible clinical correlations.
Materials and Methods: The expression patterns of 6 CTAs (MAGE A1- MA454, MAGE A3-M3H67, MAGE A4-57B, NY-ESO-1-E978, GAGE, MAGE A-6C1) and NY-BR-1 were examined by immunohistochemistry in a series of 210 non-selected patients with primary invasive breast cancer using the tissue microarray technique. The intensity of the stain was scored semi-quantitatively in a scale 0 to+3. The expression of the antigens was correlated to established clinicopathological parameters as well as disease-free (DFS) and overall (OS) survival.
Results: CTA expression exhibited a predominantly cytoplasmic and occasionally nuclear localization. At least one CTA was identified in 37.2% of cases with expression of each antigen varying from 4.5 to 15%. NY-BR-1 was positive in 46.6% of tumors, with the well differentiated tumors showing more frequent expression. MAGE A4-57B (p=0.028 and 0.015) and MAGE A3-M3H67 (p=0.001 and 0.004, respectively) positivestaining was significantly correlated to shorter OS and DFS. MAGE A1-MA454 correlated significantly only with OS (p=0.028). GAGE and MAGE A-6C1 displayed a clear trend, but not statistically significant prognostic value concerning shorter DFS and OS. In multivariate analysis only MAGE A3-M3H67 (p=0.007 OS) and MAGE A4-57B (p=0.017 DFS, 0.052 OS) showed and independent prognostic relevance. Additionally, the mortality rate increased substantially if co-expression of any 3 or more CTAs was observed.
Discussion: Our findings suggest that CTAs could serve as potential prognostic markers in primary breast cancer patients. The exclusive expression of CTAs in tumor tissues as well as the frequent expression of NY-BR-1 could define potential new targets for specific breast cancer therapies.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-10-40.
Abstract P3-10-41: Quantitative Immunohistochemical Analysis and Prognostic Significance of TRPS-1, a New GATA Transcription Factor Family Member, in Breast Cancer
Authors: Chen JQ , Litton J , Xiao L , Zhang H-Z , Warneke CL , Wu Y , Shen X , Sahin A , Katz R , Murray JL , Radvanyi L. 
Published: April 2011

Abstract
The Trichorhinophalangeal Syndrome-1 gene (TRPS-1) is a novel GATA transcription factor family member expressed in &gt;90% of human breast cancers. In this study, we developed a new quantitative IHC (qIHC) method to study TRPS-1 as a possible indicator ofprognosis in BC. Using this method, a quantitative parameter for TRPS-1 expression called a Quick Score (QS) was derived from the measured Labeling Index (LI) and Mean Optical Density (MOD) after IHC and applied to a set of 152 Stage II/III BC patients from 1993-2006 who did not receive preoperative chemotherapy. Although highly prevalent in BC, a wide range of TRPS-1 QS was found among the sample set with higher TRPS-1 QS significantly associated with tumor ER-alpha (p= 0.023 for QS, and p= 0.028 for Allred score), PR (p= 0.009), GATA-3 (P&lt;0.0001), and E-cadherin (p&lt; 0.001). TRPS-1 QS was also positively associated with HER2 status (p=0.026). Analysis of different ductal structures revealed that TRPS-1 was expressed at low levels in normal ducts and in usual ductal hyperplasia, but showed a marked increase in DCIS and invasive carcinoma lesions. An analysis of TRPS-1 expression in association with overall survival revealed that TRPS-1 QS (≥4.0) was significantly associated with improved survival (p=0.0165). Patients with TRPS-1 QS &lt;4 had a hazard ratio of 2 (p=0.019) after univariate Cox proportional hazards analysis. Further analysis of the patient samples revealed an ER-/lo, HER2+ (amplified) BC subset in which TRPS-1 expression above a critical quantitative threshold was predictive of greatly improved survival (median survival not reached after 10 years), while patients in this subset with TRPS-1 expression below this threshold having a median survival of less than 5 years. In summary, this new qIHC approach revealed critical differences in TRPS-1 expression in primary BC samples and found that this new GATA family member may be a promising positive prognostic marker that may regulate BC progression. In addition, TRPS-1 may also be a relevant new marker in a luminal ER-/low, HER2+ BC subset.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-10-41.
Abstract P3-11-10: Risk Factors for Pregnancy-Associated Breast Cancer: A Report from the Nigerian Breast Cancer Study
Authors: Huo D , Hou N , Ogundiran T , Olopade OI. 
Published: April 2011

Abstract
Background: It is known that pregnancy has a dual effect on breast cancer risk, with increased risk of breast cancer in short term and decreased risk in the long run. Pregnancy-associated breast cancer (PABC), occurring during pregnancy and several years postpartum, has poor prognosis and is challenging in clinical management. However, risk factors for PABC, except for pregnancy per se, are less understood. Other reproductive factors including age at menarche and age at first live birth may play important roles in the development of PABC.
Methods: The study is based on the Nigerian Breast Cancer Study, a case-control study of breast cancer conducted in Ibadan, Nigeria, between 1998 and 2009. In-person interviews were conducted using structured questionnaires to collect detailed epidemiologic data. Pre-menopausal women who were 50 years old or younger were eligible to this analysis. The breast cancer cases were divided in two groups: PABC (diagnosed during pregnancy or within 5 years postpartum) and non-PABC. Polytomous logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CI), contrasting each group of cases versus controls. Age in 3-year category, ethnicity, education, family history of breast cancer, history of benign breast disease, hormonal contraceptive use, alcohol drinking, height, and body mass index were adjusted in the multivariate models.
Results: In total, 1440 women were eligible to this study, including 311 PABC cases, 357 non-PABC cases, and 772 healthy controls. In the multivariate analysis adjusting aforementioned potential confounders, age at menarche was inversely associated with non-PABC (p=0.002, Table 1) but only trend towards significance for PABC (p=0.12). Age at first live birth was associated with lower risk of non-PABC but was associated with elevated risk of PABC.
Table 1. Odds ratios and 95% confidence intervals for PABC and non-PABC
Conclusions: We found menarche at older age may be protective against all premenopausal breast cancer, but age at first live birth has different role in the development of pregnancy-associated breast cancer and other premenopausal breast cancer in Nigerian women. The findings suggest that the trend towards delayed child-bearing may increase in the occurrence of breast cancer complicated by pregnancy.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-11-10.