bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular Characterization of Breast Cancer Core Biopsy Specimens by Gene Expression Analysis Using Standardized Quantitative RT-PCR.
Authors: Anderson J. , Shak S. , Millward C. , Labusch M. , Chen I. , Watson D. , Baehner F. 
Published: December 2010

Abstract
Background: Core biopsies (CBx) are increasingly the initial diagnostic procedure of choice for breast masses. Clinical studies of the 21 gene assay, which was optimized for small amounts of fixed paraffin-embedded tumor tissue, have been performed on core biopsies in the neoadjuvant setting (Gianni et al, JCO 2005 and Chang et al, Br Cancer Res Treat 2008). We report here the results of pathology review and quantitative RT-PCR analysis of a large number of CBx in clinical practice.Methods: Cases included all Oncotype DX tests reported by the Genomic Health laboratory from July 15, 2005 through May 31, 2009. Pathology review of H and E stained sections, manual microdissection, RNA quantification, and quantitative RT-PCR analysis for each gene were performed according to the pre-specified eligibility criteria and methods used in the NSABP and Kaiser Permanente clinical validation studies. Descriptive analysis was performed on de-identified data with IRB approval.Results: There were 103,863 submissions to the clinical laboratory, of which 11,757 (11.3%) were identified on pathology review as CBx. The initial submission success rate was 94.3% on all cases, and was slightly lower in the CBx (91.6%) than in surgical resections (SRx) (95.7%). The most common reason for initial failure was insufficient tumor or no tumor found in 5.6% of CBx and 3.0% of SRx. Insufficient RNA (&lt;275 ng) was found in 2.6% of CBx and 0.3% of SRx. Other causes of failure, such as RT-PCR process failures, were uncommon. In 80% of cases of initial failure another specimen was submitted by the site; the success rate on the resubmissions was 80% for both initial CBx and initial SRx. Thus, the overall success rate was &gt;97%. As expected, the rate of manual microdissection to remove non-tumor elements was higher in SRx than CBx (33.0 vs 3.9% of cases). In addition, the total yield of RNA, on average, was greater in SRx than CBx (4.2 µg vs 2.5 µg). The average Recurrence Score (RS) in CBx and SRx was similar - RS mean (±SD) = 18.9 (±12.4) in CBx and 19.7 (±11.3) in SRx. A wide range of RS was observed in CBx. The proportion of tumors with RS &lt;18, 18 - 30, and ≥ 31 was 58.8%, 28.6%, and 12.6% in CBx and 52.3%, 35.6%, and 12.1% in SRx. The distributions of quantitative ER, PR, and HER2 in CBx were also similar to SRx.Conclusions: This large study indicates that quantitative RT-PCR analysis can be successfully performed on breast cancer core biopsies. Rigorous pathology review prior to gene expression analysis to identify cases with insufficient or no tumor is required to ensure the quality of gene expression analysis.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6021.
Factors, Predicting Failure of Adjuvant Hormonotherapy of Breast Carcinoma. A Study in Tamoxifen Treated Patients.
Authors: Petrakova K. , Nenutil R. , Grell P. , Palacova M. , Vyzula R. 
Published: December 2010

Abstract
Background: The latest clinical trials indicate better performance of aromatase inhibitors, compared to tamoxifen, in adjuvant hormonotherapy of breast carcinoma. The identification of molecular markers, predicting resistance to tamoxifen, could help to identify patients, which are most likely to benefit from aromatase inhibitors in up-front adjuvant hormonotherapy.Material and methods: Tissue microarrays were constructed from archival paraffin blocks of primary tumors of 179 patients with estrogen receptor positive operable breast carcinoma in stage I-III, subsequently treated with tamoxifen for five years or until relapse, with at least 7 years follow up available. The amplifications of Her-2 and cyclin D1 genes were evaluated by fluorescence in-situ hybridization. The level of progesterone receptor (PR) and Ki67 were estimated by immunohistochemistry.Results: 54 of above patients recurred during follow up. In univariate analysis of disease free survival, the presence of more than three nodal metastases (RR=4,5 p&lt;0,001), grade 3 (RR=2,3 p=0,035), cyclin D1 (RR=3,06 p&lt;0,001) and Her-2 (RR=3,06 p&lt;0,001) amplifications were identified as significant risk factors, together with the negativity of PR (RR=2,1 p=0,013). In multivariate analysis, only clinical stage III (RR=2,6 p=0,003), cyclin D1 (RR=2,7 p=0,001) and Her-2 (RR=2,1 p=0,014) amplifications proved significant. In 77 patients who received adjuvant chemotherapy no statistically significant risk factor was identified. In multivariate analysis of 102 patients without adjuvant chemotherapy only stage III (RR=6,9 p=0,001) and Her-2 amplification (RR=4,5 p=0,001) were confirmed.Discussion: The advanced clinical stage, cyclin D1 and Her-2 gene amplifications represent factors, predicting the failure of adjuvant tamoxifen treatment, but their predictive value is much lower in patients receiving adjuvant chemotherapy. This fact indicates, they can reflect the common biological aggressiveness of tumor and need not to be tamoxifen specific.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6031.
The Relationship between Pre-Operative Biomarkers of Inflammation, Clinicopathological Characteristics and Cancer Specific Survival in Early Breast Cancer.
Authors: Obondo C. , Mansell J. , Afra A. , Doughty J. , Lannigan A. , McMillan D. 
Published: December 2010

Abstract
Breast cancer is the second most common malignancy in women. Established prognostic factors include tumour size, grade, nodal involvement, and hormonal receptor status. Recently, the systemic inflammatory response (as evidenced by elevated C-reactive protein and low serum albumin) has been established as an independent predictor of survival in patients with metastatic breast cancer (1). However, the relationship between these systemic inflammatory markers, clinicopathological characteristics and cancer specific survival has not been established in early breast cancer.During the period June 2001 to May 2008, patients with early breast cancer presenting to two hospitals in the West of Scotland were prospectively included into this study (n=959). Preoperative C-reactive protein, albumin and clinico-pathological data were recorded for each patient. The thresholds for normal C-reactive protein and albumin were taken as &lt;6 mg/l and &gt;43g/l respectively.The median follow-up of the survivors was 4.1yrs. During this period, 93 patients died of their cancer. On multivariate analysis, tumour size (HR 2.03; 95%CI 1.41-2.91, P&lt;0.001), lymph node status (HR 2.23; 95%CI 1.45-3.41, P&lt;0.001), hormone receptor status (HR 1.58; 95%CI 1.24-2.00, P&lt;0.001) and albumin &lt;43g/l (HR 1.97; 95%CI 1.28-3.01, P=0.002) were significant independent predictors of cancer-specific survival. Lower serum albumin concentrations (&lt;43g/l) were associated with deprivation (P=0.019) and significantly poorer 5-year cancer-specific survival (85 vs 92% P=0.005).The results of the present study show that lower preoperative albumin concentrations, but not elevated C-reactive protein concentrations, predict cancer-specific survival, independent of clinico-pathologic status in early breast cancer. Further, evaluation of the pre-operative systemic inflammatory response and outcome in patient subsets is warranted.1. Al Murri AM, Wilson C, Lannigan A, Doughty JC, Angerson WJ, McArdle CS, McMillan DC. Evaluation of the relationship between the systemic inflammatory response and cancer-specific survival in patients with primary operable breast cancer.Br J Cancer. 2007;96:891-5
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6033.
Sequential Treatment with Epirubicin/Cyclophosphamide, Followed by Docetaxel Is Equieffective, but Less Toxic Than FEC120 in the Adjuvant Treatment of Breast Cancer Patients with Extensive Lymph Node Involvement: The German ADEBAR Phase III Study.
Authors: Janni W. , Harbeck N. , Sommer H. , Rack B. , Augustin D. , Simon W. , Jueckstock J. , Wischnik A. , Annecke K. , Hepp P. , Friese K. , Kiechle M. 
Published: December 2010

Abstract
Background: Based on meta-analytic evidence, taxane containing adjuvant chemotherapy has been established as standard treatment in node-positive breast cancer. However, in the MA-21 study, adriamycin-cyclophosphamide, followed by paclitaxel (AC-P) was significantly inferior to the gold standard of anthracycline treatment, FEC120 (Burnell, SABCS 2006). We prospectively compared a sequential epirubicin-docetaxel chemotherapy regimen to FEC120.Patients and Methods:The ADEBAR study was a multicenter phase III trial (n=1502) to evaluate whether breast cancer (BC) pts with &gt; 3 axillary lymph node metastases benefit from a sequential anthracycline-docetaxel regimen (E90C–D: 4 cycles epirubicin [E] 90 mg/m2 plus cyclophosphamide [C] 600 mg/m2 q21 days followed by 4 cycles docetaxel [D] 100mg/m2 q21 days) compared to dose-intensive anthracycline-containing polychemotherapy (FE120C: 6 cycles E 60 mg/m² d 1+8, 5-FU 500mg/m² d 1+8 and C 75 mg/m² d 1-14, q4 weeks). The median follow-up time was 47 mts.(range 2-83 mts).Results:Treatment was stopped prematurely in 3.7% of the pts in the E90C–D arm and in 8.0% in the FE120C arm due to toxicity (p=0.0009). Antibiotic treatment was given in 10.4% (E90C–D) vs. 19.7% (FE120C), G-CSF support in 39.2% vs 61.4 % and erythropoietin stimulation in 8.7% vs. 20.0%, respectively (p&lt;0.0001). Haematological toxicity (leucopenia, neutropenic fever, thrombocytopenia, anemia) was significantly higher in the FE120C-arm.At the time of the current analysis, 281 events of recurrence of breast cancer, were observed: 128 events in the FE120C group and 153 in the E90C–D group. The unadjusted hazard ratio (HR) was 0.88 (95 percent confidence interval, 0.694 to 1.115; p=0.2197, log-rank test). Overall survival in the two groups was not significantly different: (84 deaths with FE120C vs. 88 with E90C–D (HR 0.999, 0.738-1.352, p=0.99). Subgroup analyses, stratifying for tumor size, lymph node involvement, hormone receptor and HER2-neu status showed no significant difference between the two treatment arms.Conclusion:Different toxicity profiles given, hematological toxicity in the FE120C group was more severe than in the E90C–D.In contrast to AC-P in earlier studies, EC-Doc provides a feasible and effective alternative option to dose-intensified FEC with different saftey profile in this high risk breast cancer cohort.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 604.
Cyclin B1 Is an Independent Prognostic Proliferation Marker with a High Reproducibility in a Population-Based Lymph Node Negative Breast Cancer Cohort.
Authors: Niméus-Malmström E. , Koliadi A. , Ahlin C. , Holmqvist M. , Holmberg L. , Amini R. , Jirström K. , Wärnberg F. , Blomqvist C. , Fernö M. , Fjällskog M. 
Published: December 2010

Abstract
Purpose: A large proportion of women with lymph node negative breast cancer treated with chemotherapy do not benefit from such treatment. Proliferation markers can recognize patients at high risk for recurrence. However, no proliferation marker is generally accepted for clinical use. We investigated the independent prognostic importance of cyclin B1 in node negative breast cancer and included a study of the reproducibility.Study Design: In a population-based, case-control study, 190 women who died from breast cancer were defined as cases and 190 women alive at the time for the corresponding case's death as controls. Inclusion criteria were tumor size ≤ 50 mm, no lymph node metastases, and no adjuvant chemotherapy. Tumor tissue was immunostained for cyclin B1. Two investigators evaluated the staining independently by counting approximately 100, 200, 500, and 1000 cells.Results: Cyclin B1 was statistically significantly associated to breast cancer death, in both uni- and multivariate analyses (adjusted for tumor size, age, and endocrine therapy), with odds ratios 2-3 for both investigators. The reproducibility between the two investigators was good to very good, regardless of the number of counted cells (kappa values between 0.74 and 0.82).Conclusions: Cyclin B1 is a prognostic factor for breast cancer death in a population-based and node negative patient cohort and can identify high-risk node negative patients with a good to very good reproducibility.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6051.
A Retrospective Analysis of Risk Factors of Central Nervous System Metastases in Operable Breast Cancer: Different Survival by Biological Subtype and Ki67 Overexpression.
Authors: Ishihara M. , Mukai H. , Onozawa M. , Nihei K. , Shimada T. , Wada N. , Nagai S. 
Published: December 2010

Abstract
Background: New agents have improved systemic disease control, but the control of central nervous system (CNS) metastases is still insufficient. The identification of factors that may predispose to CNS metastases may help lead to earlier detection possibly to improvement in disease management.Methods: Patients (pts) with metastatic who were diagnosed with clinical stage I-III primary breast cancer at National Cancer Center Hospital East from January 2003 to December 2005 were screened. All pts with CNS metastases were identified by CT or MRI. Cox proportional hazards models were fitted to find risk factors of CNS metastases. Factors included age, menopausal status, clinical stage, T stage, histological grade, lymphovascular invasion, hormone and HER2 status, and Ki67 (at least 30% tumor cells positive). Survival was calculated by the Kaplan-Meier method.Results: Median follow-up from operation was 53.5 months. Of 591 breast cancer pts, 76 pts (12.9%) relapsed. Seventeen pts (2.9%) developed CNS metastases; 5 pts developed as the first recurrence site. Multivariable analysis indicated the higher risk for developing CNS metastases were triple negative (TN) tumors (HR 5.532, 95% CI 1.445-21.180, p=0.013) and Ki67 overexpression (HR 3.906, 95% CI 1.179-12.939, p=0.026). There were no statistically significant differences in other factors. CNS metastasesCumulative incidence of CNS metastases (4 yrs)Median duration to CNS metastases (Months)Overall survival (4 yrs)Disease free survival (4 yrs)TN9.7% (9/93 pts)9.4%11.378.5%73.3%HER2 positive3.7% (4/107 pts)4.4%20.391.0%84.9%Others1.0% (4/391 pts)0.8% (p&lt;0.0001)24.197.5% (p&lt;0.0001)92.4% (p&lt;0.0001) Ki67 ≥30%8.6% (12/140 pts)9.4%12.382.4%75.0%Ki67 &lt;30%1.1% (5/446 pts)0.7% (p&lt;0.0001)23.996.7% (p&lt;0.0001)92.0% (p&lt;0.0001) Discussion: In our analysis, TN or Ki67 overexpression breast cancer showed earlier CNS metastases and shorter overall survival. In case of these tumors, there is higher probability for early detection of limited CNS metastatic involvement.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6053.
Prognostic Value of mib-1 in Patients with Early Invasive Breast Cancer and Its Correlation with Other Biologic Parameters in a Monoinstitutional Series.
Authors: Ferro A. , Barbareschi M. , Eccher C. , Caldara A. , Frisinghelli M. , Triolo R. , Aldovini D. , Pellegrini M. , Bernardi D. , Galligioni E. 
Published: December 2010

Abstract
INTRODUCTION: Mib-1 is a proliferation biomarker and a prognostic factor for breast cancer as reported in several studies.PURPOSE: The aim of the present study was to examine interactions between mib-1 and other clinical-pathological markers and their impact on outcomes in early invasive breast cancer.PATIENTS AND METHODS: Mib-1 was identified by immunohistochemical staining in 2660 EIBC patients treated in our institution from 2000 to 2008. Mib-1 was dichotomized at the value of 20%. Correlation between mib-1 (&gt; or ≤10620%) and age, tumour size (T), nodal status (N), ER, PR, HER-2, grading (G) was performed by χ2 test. Log-rank test and Cox regression model were performed to test mib-1 as prognostic factor for overall survival (OS) and Disease Free Survival (DFS) and evaluate its correlation with other known prognostic factors.RESULTS: Mib-1 was &gt; 20% in 1276 and ≤106 20% in 1384. Mib-1&gt; 20% was significantly (p=.000) associated with younger age, greater size, positive lymph nodes, poor grading, absent or low ER and/or PR expression level, HER-2 over-expression or amplification with or without co-expression of ER and/or PR, triple negative subtypes. Mib-1 was a significant predictor of worse DFS and OS (p=.000). At a median follow up of 32 months the DFS and OS were 97.4 and 99.2% respectively in Mib-1 ≤20% group and 92.4 and 97.2% respectively in Mib-1 &gt; 20%. There were 195 relapses (7,3%): 139 (5.2%) in Mib-1 &gt; 20% and 56 (2.1%) in Mib-1 ≤ 20%. Breast cancer related deaths were 74 (2.8%) with 58 (2.2%) in mib-1 &gt; 20% group and 16 (0.6%) in mib-1 ≤ 20%.Mib1 &gt;20% was predictive of poorer prognosis in &gt; 40 years patients, small tumors (T1), lower grading (G1 and G2), positive ER and/or PR group with high or intermediate expression, negative HER-2 tumors. However, in Cox multivariate analysis mib-1 didn't maintain independent prognostic value.CONCLUSIONS: In our experience, Mib-1 confirms to be a significant prognostic biomarker for DFS and OS in early breast cancer. It could provide additional information beside other clinico-pathological parameters to perform the risk stratification of early breast cancer patients.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6054.
The Early Prediction of Response to Neoadjuvant Chemotherapy Using MRI.
Authors: Kim H. , Ko E. , Kim E. , Jo E. , Kim M. , Noh W. 
Published: December 2010

Abstract
Purpose: Neoadjuvant chemotherapy is an effective method for down-staging the primary tumor before surgery. However, some of patients do not respond. In these patients, neoadjuvant chemotherapy is just an ineffective, toxic and expensive procedure. Therefore, it is very important to find the reliable method to differentiate the responder from non-responder as early as possible. In order to evaluate the role of magnetic resonance imaging (MRI) for the assessment of tumor response, we examined the correlation between the early MRI changes after the 1st cycle of neoadjuvant chemotherapy and later pathologic response after the 3rd cycle of neoadjuvant chemotherapy.Patients and method: 31 breast cancer patients who underwent neoadjuvant chemotherapy prior to surgery were analyzed. The baseline MRI was taken before neoadjuvant chemotherapy. Anthracycline plus taxane were administered to all patients. Post-chemotherapy MRI assessment was done just before the 2nd cycle of neoadjuvant chemotherapy. If the primary tumor was reduced more than 20% in the product of the longest and perpendicular diameter, those cases were classified as responders. Surgery was performed after the 3rd cycle of neoadjuvant chemotherapy. The pathologic response was assessed by measuring pathologic tumor size of viable tumor cells. Sensitivity, specificity, positive predictive value, and negative predictive value of MRI findings were calculated on the basis of histopathological examination.Results: Total 31 patients were examined. Of these patients, 2 patients had bilateral breast cancer. Therefore, a total of 33 lesions were evaluated. The median tumor size on baseline MRI was 4.5cm (range:2.1-10.0cm). 27 cases were classified as responders on early MRI findings. Of these cases, pathologic response was confirmed in 26 cases after surgery. Six cases were classified as non-responder on MRI. In this group, 3 cases showed pathologic response and 3 cases did not. Sensitivity, specificity, positive predictive value and negative predictive value of early MRI findings for the prediction of pathologic response were 89.7%, 75.0%, 96.3% and 50.0%, respectively.Conclusion: Post-chemotherapy MRI after the 1st cycle of neoadjuvant chemotherapy could differentiate responders from non-responders with high accuracy. It would be helpful to determine whether the chemotherapy regimen should be continued or not in the early phase of neoadjuvant therapy.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6057.
Interaction between Family History of Breast Cancer and the Remaining Gail Risk Factors.
Authors: Ni X. , Muram D. 
Published: December 2010

Abstract
Background: The Gail breast cancer risk assessment model takes into account the relative contribution of various breast cancer risk factors (RF) and provides 5-year and lifetime breast cancer risk estimates. The purpose of this analysis was to determine the relative contribution of the Gail model RF in patients with and without family history of breast cancer (FHBC).Materials and Methods: Patients from the RUTH trial, consisting of postmenopausal women with or at high risk for coronary artery disease (CAD), were included in this analysis, with the exception of women ≥86 years of age or with medical history of any breast cancer, ductal carcinoma in situ, or lobular carcinoma in situ. Patients with missing values for RF were also excluded. For the resulting study population (N=10015), the risk score was calculated using the breast cancer risk assessment (BCRA) tool from the National Cancer Institute. A descriptive analysis of the BCRA risk scores for each RF stratified based on the presence or absence of a FHBC was performed. Risk factors were categorized as follows: advancing age (&lt;65 or ≥65; 65 was the mean age); age at menarche (&gt;12 or ≤12), number of biopsies (None or ≥1), age at first live child birth (&lt;30 or ≥30; nulliparty included in &lt;30 group per model). Interaction plots based on the two-way analysis of variance (ANOVA) model were generated for each category of the RF.Results: Of the 10015 women, 9123 (91.1%) did not have FHBC, while 892 (8.9%) did. Among women without FHBC, the mean BCRA score (%) was 1.54±0.40; 62.2% were 65 years or older, 28.8% had early menarche, 8.4% had first child at ≥30 years of age, and 8.1% had a previous breast biopsy. Among women with FHBC, mean BCRA score was 3.46±1.24; 70.3% were 65 years or older, 30.4% had early menarche, 9.3% had first child at ≥30 years of age, and 15.4 % had a previous breast biopsy. A statistically significant (p&lt;0.001) amplification in the risk conferred by advancing age, previous biopsy, and early menarche was observed in patients with FHBC compared with patients with no family history for the disease (Figure 1). In contrast, the relative contribution to risk by late childbearing is more pronounced (p&lt;0.001) in patients without FHBC.Discussion: Family history is an independent and important determinant of breast cancer risk in postmenopausal women. Other RF have a different influence on the overall risk estimate in women with FHBC when compared to women without FHBC. Increased risk was observed for advancing age, early menarche, and previous breast biopsy. A different pattern was seen for late childbearing. While the data were obtained from a large cohort of women, further analysis may be required to determine if these results are generalizable for all women regardless of menopausal status or CAD.Figure 1. Mean BCRA risk within each risk factor group, stratified by FHBC.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6062.