bluuebunny/crossref_metadata_2025_split huggingface dataset:
Breast Cancer in Young Women: The University of New Mexico Cancer Center (UNMCC) Experience.
Authors: Movva S. , Ballinger L. , Saiki J. , Royce M. 
Published: December 2010

Abstract
Background: While only a small proportion of breast cancer is attributable to hereditary susceptibility, identifying high-risk individuals is essential for appropriate medical management. Furthermore, identifying individuals with inherited breast cancers have significant impact on both patient and their family. Beyond early age of onset, family history of multiple cancers may warrant a referral to cancer genetics professional. However, in a busy oncology practice, documentation of a full family history can be time consuming and referral opportunities for genetic counseling may be missed. In this study, we evaluated the strength of family history documentation in breast cancer patients' charts, and whether or not appropriate referrals to the Hereditary Cancer Assessment Program (HCAP) were made. Racial differences in these referral patterns were also assessed.Materials and Methods: All charts of patients last known to be living as of 03/29/06 per the UNMCC Tumor Registry with an invasive breast cancer who were 40 years old or younger at the time of diagnosis were reviewed. Baseline data included patient age at diagnosis, self-reported ethnicity, histology, bilaterality and cancer status. The presence or absence of family history of breast and other cancers, and referral to the HCAP was documented. Descriptive statistics were performed on baseline data. Correlative analyses were conducted to note any racial differences in referral to HCAP.Results: A total of 211 women met inclusion criteria. Patients in the Tumor Registry were seen at diagnosis at UNMCC from 01/01/67 through 12/31/04. Mean age was 35. Racial distribution was similar to that of the New Mexican population: 44% Caucasian, 41% Hispanic, 10% Native American (NA) and 3% African American. Predominant histology was infiltrating ductal carcinoma (79%); 10% of women had a second breast primary. 63% of women had a positive family history of cancer; however, family history was not recorded in 17%. After HCAP was established, 109 women were eligible for referral, yet 68 (62%) of women had not been referred for genetic counseling. Only 39% of Caucasian, 40% of Hispanic and 34% of NA eligible women were referred.Discussion: Women under the age of 40 at time of breast cancer diagnosis are more likely to have a hereditary cancer syndrome. In our population, 17% of women had no documentation of family history, and almost 70% were never referred for hereditary counseling. There was no difference in referral patterns among different racial/ethnic backgrounds. On the basis of this review, quality improvement initiatives were undertaken to improve referral patters of young women with breast cancer for genetic counseling and potential genetic testing.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4079.
Study of Neurobehavioral Symptoms and Impairments in Breast Cancer Patients Receiving Adjuvant Aromatase Inhibitor Therapy.
Authors: Weaver J. , Stark S. , Stark S. , Shahverdi K. , Jeter S. , Zorzi J. , Skolasky, Jr R. , Skolasky, Jr R. , Andrejczuk M. , Stearns V. , Gordon B. , Gordon B. 
Published: December 2010

Abstract
Background: Whether treatment with aromatase inhibitors (AI) may be associated with the development of cognitive or other mental impairments is under debate. Few studies have carefully assessed AI-associated changes in cognitive function, and none have assessed differences between the three third-generation AIs – anastrozole, letrozole, and exemestane. We initiated a prospective clinical trial to compare baseline and 1-year change in neurophysiological testing in women initiating adjuvant AI.Patients and Methods: Women with a hormone receptor-positive stage 0-III breast cancer who were about to begin AI treatment were eligible for enrollment. We compared intra-individual neurophysiological testing results at baseline (Session I) and following one year of AI (Session II). Cognitive/behavioral assessment included standardized tests sensitive to 8 neuropsychological domains: General Intelligence, Attention, Perceptual-motor Performance, Working Memory, Visual Long-term Memory, Verbal Long-term Memory, Language, and Executive Functioning. Scoring was based upon age- and education-adjusted normative data. In addition, participants completed several subjective reports of cognitive, physical, and emotional functioning.Results: To date, 53 subjects enrolled in Session I, and 30 completed Session II. Analysis of the 30 women who completed both sessions revealed statistically significant differences (with the significance level set at p=0.05, test-wise), including: impairment from Session I to Session II on the PASAT Trial I (p=0.005) and improvement from Session I to Session II on the following tests: FAS Total (p&lt;0.001); Animal Naming (p=0.025); RAVLT I-V, B, Delay, and Immediate (p&lt;0.001 for all); RAVLT 5-1 (p=0.017); RAVLT % (p=0.022); Logical Memory I (p=0.005) and II (p&lt;0.001); WMS-Faces I & II (p&lt;0.001 for both); WAIS-Picture Completion (p=0.027); and WAIS-Vocabulary (p&lt;0.001).Discussion: Only a few studies have examined the effect of AI treatment on cognitive functioning. Findings from the present study suggest that, following the administration of AI for 1 year, women as a group appear to exhibit impairments in attention (as evidenced by PASAT performance) and possibly in executive functioning. However, there was also improved performance in the areas of language, verbal long-term memory, and visual long-term memory. These preliminary results suggest a need to be sensitive to the possibility that AI treatment may have mixed effects on cognitive and related behavioral functions.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4084.
A Randomised Study Comparing the Effects of Adjuvant Anastrozole (A), Letrozole (L) and Exemestane (E) on Lipid Metabolism.
Authors: McCaig F. , Renshaw L. , Williams L. , Young O. , Murray J. , Macaskill E. , McHugh M. , Riermersma R. , Evans D. , Dixon J. 
Published: December 2010

Abstract
Background:Aromatase inhibitors (AIs) reduce circulating oestrogen which may have a detrimental effect on lipid metabolism and subsequently ↑ cardiovascular risk. This study compares the effects of adjuvant A, L and E on lipid metabolism.Patients and Methods:This was an open, randomised pharmacodynamic study. Plasma lipids were measured in 120 postmenopausal women with invasive ER +ve breast cancer. As part of their adjuvant hormone therapy, patients were randomized to receive either:• 4 months of A or• 4 months of L or• 4 months of EFasting blood and urine samples were collected at the same time of day on each of (a) the day of entry, (b) after 3 months and (c) after 4 months. Patients were then switched to tamoxifen (T) and further samples collected after 12 months.• Triglycerides, cholesterol, ApoB and cLDL were measured.↑ levels are associated with ↑ cardiovascular risk.• ApoA-1 and HDL were also measured.↑ levels are associated with ↓ cardiovascular risk.Analyses were performed using repeated measures or analysis of covariance.ResultsDifferences between A vs L vs ETriglycerides E significantly ↓ triglycerides. There was a borderline significant difference between the drugs (p=0.055).Cholesterol E significantly ↓ cholesterol (p=0.03).ApoB No significant changes were detected.cLDL No significant changes were detected.ApoA-1 There were no significant differences detected between A or L although the fall with E was less but not significantly different to A or L (p=0.08).HDL E significantly ↓ HDL (p=0.008).Differences between steroidal vs non-steroidal AIsTriglyceride and ApoA-1 levels fell significantly more with E compared to the non-steroidal A+L (p=0.02, p=0.045 respectively).Effects of tamoxifenChanges from baseline after treatment on AIs and subsequent treatment with TFollowing T there was no evidence to suggest that the changes from baseline were influenced by the type of AI that patients received.Changes from end of treatment on AIs and subsequent treatment with TT increased HDL by a statistically significant greater amount following E than it did after A or L (p=0.009). From the end of treatment with AIs, T produced significant rises in triglyceride (p=0.0001), HDL (p=0.006) and ApoA1 (p=0.0003), and significant falls in cholesterol (p=0.03) and cLDL (p&lt;0.0001).Conclusions:There were no significant differences between letrozole, anastrozole and exemestane and their effects on cholesterol, HDL, cLDL or ApoB.There was a significant difference between steroidal and non-steroidal in their effect on triglycerides and ApoA1.Tamoxifen had significant effects on lipids lowering cholesterol and cLDL and increasing triglycerides HDL and ApoA-1.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4086.
Letrozole in Combination with Trastuzumab Is Superior to Letrozole Monotherapy as First Line Treatment in Patients with Hormone-Receptor-Positive, HER2- Positive Metastatic Breast Cancer (MBC) – Results of the eLEcTRA Trial.
Authors: Huober J. , Fasching P. , Paepke S. , Kubista E. , Barsoum M. , Wallwiener D. , Harbeck N. 
Published: December 2010

Abstract
Background: Letrozole (LET) and trastuzumab (TRA) are established agents for the treatment of hormone-receptor (HR) positive metastatic breast cancer (MBC) patients and HER2 positive disease, respectively. The “eLEcTRA” trial was designed to compare the efficacy and safety of LET combined with TRA to LET alone in patients that are both HER2 and HR positive. Furthermore, LET alone was compared in patients with HER2 and HR positive disease vs. those with HER2 negative, HR positive tumors.Methods: In this multicenter trial, 92 pts from 32 sites in 7 countries were enrolled from 2003 to 2007. Initially, enrollment of 370 pts was planned, however, due to slow recruitment the trial was prematurely closed in 2007. Patients with HER2 and HR positive MBC were randomized to either LET alone (Arm A, n=31) or LET + TRA (Arm B, n=26) as first-line treatment. In addition, 35 patients with HER2 negative and HR positive tumors were assigned to receive LET alone as first-line treatment (Arm C). Tumor response assessments were based on RECIST. Primary endpoint was time to progression (TTP), secondary endpoints were overall response rate (ORR) and clinical benefit rate (CBR).Results: Median age in the three arms was 61 (arm A), 61,5 (arm B), and 70 years (arm C), respectively. Median TTP in the LET alone arm (A) was 3.3 months compared to 14.1 months in the LET + TRA combination arm (B) (hazard ratio=0.67; p=0.23) and 15.2 months in arm C (hazard ratio=0.71; p=0.03). CBR was 39% for arm A compared to 65% in arm B (odds ratio 3.15, CI 1.07-9.26) and 77% in arm C (odds ratio 5.34, CI 1.83-15.58), respectively. ORRs were 13% for arm A, 27% for arm B, and 11% for arm C.LVEF as cardiac safety parameter showed no change from baseline to the minimum value during the treatment for arms A and C and a slight decrease by 5% for arm B.The incidence of other cardiac adverse events was comparable in all arms (10%, 8%, and 9%). Gastrointestinal disorders or musculoskeletal and connective tissue disorders were slightly more frequent for patients receiving LET and TRA (arm B).Conclusion: The results of the eLEcTRA trial show that the combination of letrozole and trastuzumab can be safely administered and is superior to letrozole alone as first-line therapy in patients with HER2 and HR positive MBC. Our results also confirm earlier evidence that aromatase-inhibitor therapy alone is only associated with a rather short TTP in HER2 and HR positive MBC. In contrast, outcome in letrozole-treated patients with HER2 negative HR positive tumors is significantly better compared to that associated with tumors with both HR and HER2 expression.(Trial was sponsored by Novartis Pharmaceuticals)
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4094.
A Retrospective Analysis of Primary Tumour Histology and Survival in Breast Cancer Patients Developing Symptomatic Brain Metastases Treated with Whole Brain Radiotherapy (WBRT) at Mount Vernon Cancer Centre (MVCC).
Authors: Miller R. , Assoku M. , Assoku M. , Krell D. , Sasieni P. , Mulholland P. , Mulholland P. 
Published: December 2010

Abstract
Background: The purpose of this study was to determine the influence of primary tumour histology on survival following WBRT for brain metastases in patients with breast cancer.Methods: From treatment records we identified 294 patients with brain metastases and a diagnosis of primary breast cancer who were treated with WBRT at MVCC from January 2000 until December 2008. We obtained information from case notes and original pathology reports regarding TNM staging and receptor status: Estrogen (ER), progesterone (PR) and human epidermal growth factor receptor-2 (HER-2). Dates of diagnosis and death were sourced from records at MVCC, the Thames Cancer Registry and GP practices.Results: We obtained receptor status, TNM staging and dates of death for 294 patients; 19 were excluded as date of death could not be verified. The dates of primary diagnosis for the study cohort ranged from 1983 to 2008. The median age at diagnosis was 52 (range 24-81, interquartile range 42-62).Analysis of age at primary diagnosis expressed as &lt; 50 or ≥ 50 demonstrated improved survival in the younger age group (HR 0.64 95% CI 0.50-0.83). Time to brain relapse amongst patients receiving WBRT was not related to initial tumour size (p=0.8) but was related to the number of affected nodes (reduced by 9 months per node, p=0.038) and women with (non-brain) metastatic disease at diagnosis had WBRT on average 2.4 years earlier than those that did not (p=0.004). TNM staging did not affect post WBRT survival. After adjusting for age at diagnosis (&lt;,≥50), post WBRT survival was not affected by age at treatment. Controlling for the influence of age at diagnosis, Cox regression analysis of survival post WBRT demonstrated improved survival for ER positive patients (HR 0.66 95% CI 0.49-0.90). Survival post WBRT was not significantly influenced by HER-2 (HR 0.81 95% CI 0.55-1.19) or PR (HR 0.91 95% C.I. 0.63-1.33) status. Patients who experience late brain relapse (&gt; 4 years post diagnosis) have slightly better survival post WBRT (HR 0.77, p=0.054). ER positive patients in this study developed brain metastases on average 1.8 years later than ER negative patients (95% CI 0.9-2.8).Conclusions: In this cohort ER positive patients who relapse in the brain do so later and live longer following WBRT (figure 1). Our data suggests that HER-2 status has little effect on post WBRT survival.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4110.
Evidence for Unique Mechanisms of Estrogen Receptor Degradation Elicited by Estradiol and ICI 182,780 (Fulvestrant).
Authors: Casa A. , Casa A. , Lazard Z. , Thorne C. , Ouspenskia M. , Zhang P. , Lee A. , Lee A. , Lee A. 
Published: December 2010

Abstract
Selective estrogen receptor down-regulators (SERDs), such as ICI 182780 (Fulvestrant), comprise a class of drugs that has been developed to inhibit estrogen receptor alpha (ER) activity in breast cancer. ICI is a pure antagonist that competitively binds to the ligand-binding domain of ER. The binding of ICI is thought to reduce the receptor's half-life by increasing protein turnover. However, the exact mechanism of ICI action, including whether or not receptor degradation is actually required for its antiestrogenic action, is currently unknown. Our laboratory has shown that a cytoplasmic ER mutant (ERΔNLS) lacking a nuclear localization sequence (NLS) is completely resistant to ICI-mediated degradation in both MCF-7 breast cancer cells and their ER-negative derivatives, C4-12 cells. Immunofluorescence and confocal microscopy were performed to assess localization of all ER proteins. These cells were also treated for different lengths of time with varying concentrations of both estradiol (E2) and ICI. Immunoblotting was performed to determine levels of ER protein. A competitive radioligand binding assay was also conducted to assess the ligand-binding capability of the ERΔNLS mutant receptor. Immunofluorescence and confocal imaging of stably transfected C4-12 cells has confirmed distinct subcellular localization of each ER protein. Wild-type ER localizes mainly to the nucleus, while ERΔNLS is cytoplasmic. As expected, treatment of either wild-type MCF-7 cells or C4-12 cells expressing wild-type ER with E2 or ICI caused degradation of ER protein. Treatment of MCF-7/ ERΔNLS or C4-12/ ERΔNLS cells with E2 caused degradation of ERΔNLS protein. In stark contrast, increasing concentrations of ICI failed to cause degradation of ERΔNLS. Furthermore, experiments performed in the presence of cycloheximide have shown that ICI does not modulate ERΔNLS half-life. The inability of ICI to degrade ERΔNLS is not due to an inability of ERΔNLS to bind ligand, since results from competitive radioligand binding assays show that the affinity of ERΔNLS for both E2 and ICI is equal to the affinity of wild-type ER for both ligands. We have recently cloned the SV40-NLS onto ERΔNLS, and confocal microscopy has confirmed that the SV40-NLS is sufficient to force ERΔNLS into the nucleus. I am currently using this construct to determine if it is the NLS domain itself or merely subcellular localization of ER that is important for ICI-mediated degradation. In conclusion, ER is a critical marker for response to antiestrogen therapy. Treatment with ICI is not without its shortcomings. A better understanding of the mechanism by which ICI degrades ER may lead to the development of better antiestrogen therapies to inhibit ER action with less toxicity and greater specificity.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4137.
Sumoylation of Corepressor SAFB1 – Mechanism of Action and Biological Relevance in Breast Cancer.
Authors: Garee J. , Meyer R. , Oesterreich S. 
Published: December 2010

Abstract
Scaffold attachment factor B1 (SAFB1) was originally isolated due to its ability to bind Scaffold/Matrix attachment regions of genomic DNA. Subsequently, SAFB1 has also been shown to be involved in RNA processing, chromatin organization and stress response. Work from our laboratory has shown that SAFB1 can bind and modulate transcription of the HSP-27 promoter and repress activity of ERα. Repression of ERα occurs through an independent and transferable c-terminal repression domain. Further work has indicated that SAFB1 can interact with and repress transactivation of a host of nuclear receptors including PPARg and FXR, suggesting a general role for SAFB1 in transcriptional repression.Many proteins associated with transcriptional regulation are post translationally modified by small ubiquitin like modifier (SUMO). SUMO is a 98 amino acid mature polypeptide that is added post translationally to target proteins usually within a consensus sumoylation motif, ΨKXE (where Ψ is a large hydrophobic residue, K-lysine of modification and X any residue). The process of sumoylation is analogous to ubiquitination. SUMO modification of proteins associated with transcription has generally been associated with transcriptional repression. The mechanism by which this modification leads to transcriptional repression has yet to be defined.Work by our laboratory has indicated that SAFB1 is modified by sumoylation. In silico analysis indicated two consensus sumoylation motifs within SAFB1. Immunoprecipitation studies revealed SUMO modified forms of SAFB1. Mutating the lysine's within the sumoylation motifs to arginine (K231,294R) lead to a loss of sumo modified SAFB1 indicating these as the sites of modification. Transient ERE-Tk-Luciferase assays showed a loss of transcriptional repression with over expression of SAFB1 K231,294R compared to SAFB1 wildtype. Loss of transcriptional repression was also seen utilizing transient Gal4DBD reporter assays indicating an effect of sumoylation on SAFB1's intrinsic repressive function. Co-immunopreciptation studies have indicated interaction between SAFB1 and SUMO E3 ligases suggesting these may be important for modifying SAFB1. Additionally, over expression of members of the sumoylation machinery can enhance SAFB1 repressive activity indicating this modification is important for SAFB1 transcriptional repression. Loss of SAFB1 sumoylation does not alter protein half life indicating the loss of transcriptional repression is not through this mechanism.Our studied have indicated that sumoylation of SAFB1 is important for its repressive activity. Additional studies within the lab are aimed at addressing the mechanism and the complete extent of functional consequences of sumoylation of SAFB1. A better understanding of post translational modification of SAFB1 may provide additional insights into the diverse functions of SAFB1 and its role in breast cancer.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4142.
HER2-Associated Breast Cancer Signature Using a 3D Culture Model.
Authors: Chaluvally-Raghavan P. , Zeisel A. , Koestler W. , Jacob-Hirsch J. , Rechavi G. , Domany E. , Yarden Y. 
Published: December 2010

Abstract
Background: Carcinomas of the breast account for one third of all cancers occurring in woman and responsible for approximately one quarter of cancer-related deaths in females. The HER2/Neu -oncogene is amplified in 20-25% percent of human primary breast cancers and this alteration is associated with disease behaviour. Whereas signalling pathways emanating from HER2 have been characterized, much less is known about the transcriptionally regulated genes that contribute to HER2 tumorigenic effects.Materials and Methods: Normal and HER2 overexpressing mammary epithelial cells (MCF10A) were grown in extracellular matrix to form 3D structures, which allow epithelial cells to organize into structures that resemble their in vivo architecture. RNA was isolated from the 3D structures and hybridized to an Affymetrix HuGene 1.0 ST oligonucleotide array.Results: Upon HER2 overexpression, mammary epithelial cells lost their polarity and formed disorganized structures in matrigel. Using microarrays we analyzed transcriptional events responsible for the morphological changes and found that several sets of genes such as integral proteins, transcription factors, matrix proteases and chemokines were highly altered in the HER2 overexpressing group. Using gene annotation we defined molecular-pathways which are highly altered in HER2 overexpressing cells. More generally, our study proposes a mechanistic description of the processes underlying the HER2 transcriptional network.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4146.