bluuebunny/crossref_metadata_2025_split huggingface dataset:
Randomized Double-Blind Placebo-Controlled Clinical Trial Testing Ketorolac Tromethamine for Reducing the Pain and Discomfort Experienced during Mammography.
Authors: Freitas-Junior R. , Freitas-Junior R. , Silveira-Junior L. , Tokaski W. , Ximenes C. , Rahal R. , Santos A. , Tomazini M. , Martins E. , Freitas N. 
Published: December 2010

Abstract
OBJECTIVE: To study the possibility of reducing the pain and discomfort experienced during mammography, by means of using an analgesic as premedication. PATIENTS AND METHODS: This was a randomized double-blind placebo-controlled clinical trial testing ketorolac tromethamine for reducing the pain and discomfort experienced during mammography. There were 308 participants in the study, who all signed a free and informed consent statement. Of these, 153 patients (group 1) received 10 mg of ketorolac tromethamine orally and 155 (group 2) received placebo orally, 60 minutes before undergoing mammographic examination. After taking the medication and while waiting to undergo the procedure, the patients themselves filled out a form asking about personal data and possible factors relating to pain and discomfort while undergoing mammography. After the examination, the patients subjectively assessed the pain and discomfort experienced during the examination using a visual analog scale (VAS) graded from zero to ten. The statistical analysis consisted of characterizing the groups using absolute and relative frequencies and comparing the dependent and independent variables between the groups using the chi-squared association test, with Yates correction when necessary. RESULTS: The mean VAS pain level presented by the patients was 3.36 and the median was 2.90. It was observed that 51 (16.6%) of the patients did not present any pain, 106 (34.4%) presented mild pain, 94 (30.5%) moderate pain, 40 (13%) severe pain and 17 (5.5%) intolerable pain. With regard to discomfort, 68 (54.9%) reported tolerable discomfort, 63 (20.5%) a lot of discomfort and 8 (2.6%) intolerable discomfort. Among the factors related to pain, only the presence of previous mastalgia was significant (p &lt; 0.05). Somnolence was the adverse event most present: 2.6 and 5.8% in the ketorolac and placebo groups, respectively. CONCLUSIONS: The use of 10 mg of ketorolac tromethamine did not have any influence regarding reduction of the pain and discomfort experienced by the patients during mammography, when compared with placebo. Among the factors studied, the only one associated with greater possibility of pain and discomfort while undergoing mammography was a history of mastalgia.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4014.
Invasive Lobular Carcinoma: Imaging Characteristics, Size at Presentation and Bilaterality.
Authors: Hu J. , Lanitis S. , Dimopoulos N. , Bright-Thomas R. , Cunningham D. , Faissola B. , Al-Mufti R. , Rice A. , Cleator S. , Hadjiminas D. 
Published: December 2010

Abstract
Aims: Invasive Lobular Carcinoma (ILC) is often described as elusive to standard imaging modalities and usually requiring mastectomy to obtain clear margins. Its reputation of being bilateral has been disputed by most recent studies. The aim of this study is to investigate whether the radiological diagnosis of ILC at first symptomatic presentation is more difficult than that of Invasive Ductal Carcinoma (IDC) in a modern breast clinic; also whether its size, surgical treatment at presentation and bilaterality is different from IDC and its subtypes.Materials & Methods: The radiological codes given to all new symptomatic patients with invasive breast cancer, presenting at the breast clinic of St Mary's Hospital and undergoing surgery as first treatment, (n=754), were collected prospectively between 1998 and 2005 and final mastectomy rates were also recorded. Histological reports of all synchronous and metachronous bilateral cancers presenting with at least one tumour between 1998 and 2007 were analyzed (n=65).Results: ILC was given suspicious radiological codes as often as IDC (90% vs 93%). On final histology, ILC measured on average 3.6cm compared to 2.5cm for IDC (p&lt;0.05). There was a trend of ILC requiring mastectomy more often (51% vs 43%). 12.7% of patients with at least one ILC diagnosis have developed bilateral breast cancer compared to 4.5% of patients who have never had an ILC diagnosis (p&lt;0.05).Results IDCILCMixedSpecialUnknownTotalNo of patients551 (73%)86 (11%)52 (7%)62 (8%)3 (0.4%)754Age (mean)5861596157.659Mastectomy191 (43%)36 (51%)23 (49%)13 (25%) 263Breast conservation257 (58%)36 (51%)24 (51%)41 (77%) 358Size cm (mean)2.53.62.52.0-2.7USS suspicious473 (93%)72 (90%)41 (90%)42 (76%)2 (100%)630MMG suspicious412 (81%)58 (73%)39 (80%)43 (80&)2 (100%)554 Conclusions: ILC is as easy to diagnose radiologically as IDC in symptomatic breast patients. However, ILC is larger at first presentation. In our database, ILC identified a subgroup of breast cancer patients who have a 3-fold higher risk of developing bilateral breast cancer of various histological types.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4015.
Background Enhancement Patterns on Screening Breast MRI – Impact on Biopsy Rate and Short Interval Follow Up.
Authors: Hambly N. , Morris E. 
Published: December 2010

Abstract
Introduction:Marked background enhancement is one of the perceived limiting factors on breast MRI possibly obscuring suspicious lesions and reducing both the sensitivity and specificity of detection of small cancers. Background enhancement on MRI refers to the normal physiological enhancement of the woman's fibroglandular tissue and varies with age, hormonal status, menstrual cycle and breast glandularity. Patterns of enhancement vary greatly and marked enhancement can occur even when the MRI is performed in week 2 of the menstrual cycle or in postmenopausal women.Aim:To determine what impact background enhancement has on biopsy rate and short interval follow up rate.Method:231 consecutive baseline screening MRIs, in women aged between 16 -79 (average age 48) performed between Jan 2003 and Oct 2004 were selected. Indications for screening included significant family history (46.3%), personal history of contralateral mastectomy (25.1%), personal history of atypia (19.5%), other (3.0%), personal history of mantle radiation (2.2%), personal history of breast cancer &gt; 5 years previously (2.2%), personal history of ovarian cancer (1.7%).The background enhancement in each case was described as minimal (&lt; 25% glandular tissue showing enhancement), mild (25-50% enhancement), moderate (50-75% enhancement) and marked (&gt; 75% enhancement).The BIRADS category, positive predictive value of biopsy and false positive rate was determined and compared for enhancement patterns.Results:Of 231 screening studies 26.6% demonstrated minimal enhancement, 32.8% mild enhancement, 22.7% moderate enhancement and 17.9% marked enhancement. Patients with minimal/mild enhancement had significantly higher rate of normal (BIRADS 1/2) examinations than those with moderate/marked enhancement (47.8% vs. 30.5%, p = 0.008). Patients with minimal/mild enhancement had significantly lower rate of six month followup (BIRADS 3) (38.97% vs. 53.68%, p = 0.02). No significant difference in biopsy rate was noted (11.7% minimal/mild enhancement vs. 14.7% moderate/marked enhancement, p = 0.5). No significant difference in positive predictive value of biopsy between the groups was noted (35.7% for moderate/marked enhancement vs. 25% for minimal/mild enhancement, p = 0.52).Conclusion:No significant association was found between background enhancement pattern and biopsy rate or false positive rate. However, patients with moderate/marked enhancement were significantly more likely to be given a category of BIRADS 3 and assigned to short interval follow up. The increased rate of BIRADS 3 in patients with moderate/marked background enhancement may be related to reduced reader confidence in these patients. Recognition of normal background enhancement patterns is important to limit the number of patients undergoing short interval followup.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4020.
Dynamic Breast Magnetic Resonance Imaging in the Assessment of Breast Glandular Tissue in High Risk Patients after Prophylactic Ovariectomy.
Authors: Vilar V. , Dromain C. , Caramella C. , Delaloge S. , Caron O. , Uzan C. , Balleyguier C. 
Published: December 2010

Abstract
Purpose: To evaluate the enhancement of breast glandular tissue by dynamic magnetic resonance imaging (MRI) in high risk patients, before and after prophylactic ovariectomy.Materials and Methods: A retrospective study was performed on 28 patients with high risk for breast and ovarian cancer who underwent preventive bilateral ovariectomy. Seven patients who were at hormone replacement therapy and chemotherapy were excluded. From the 21 patients included, 12 were BRCA 1; 6 were BRCA 2; 1 was BRCA 1 – 2; and 2 patients had strong familiar history. All patients underwent contrast breast MRI before and after surgery, for breast cancer screening. MRI was performed at GE Healthcare 1.5 Tesla equipement before (mask) and after 5 phases of contrast injection. All pre contrast images were subtracted from the post contrast images. The second subtracted sequences of MRI images were analyzed qualitatively according to the type of glandular enhancement (1. no enhancement, 2. mild homogeneous, 3. strong heterogeneous, 4. strong homogeneous, 5. mild heterogeneous), and quantitatively by measuring signal intensity of glandular tissue in the upper outer quadrant of the breast in the second sequence of post-contrast images. Patients were divided into 2 groups: with and without the appearance of a lesion between the first and second MRI, for comparative analysis with the fibroglandular tissue.Results: Mean age was 44 years (39-51). In qualitative analysis at MRI before ovariectomy (MRI 1), 33% of the patients showed type 3 enhancement; 33% type 5; 29% type 4 and 5% type 1. At MRI post-ovariectomy (MRI 2), 67% of the patients presented enhancement type 1; 19% type 4 and 14% type 3. Twenty patients showed a higher enhancement at MRI 1 and for 1 patient the enhancement was the same at MRI 1 and 2. In quantitative analysis, the average of enhancement of the glandular tissue at MRI 1 was 356.1 and for MRI 2 was 65.2. Three patients presented an enhanced nodule on the first and second MRI. The average of enhancement of the lesions at MRI 1 was 890.9 and at MRI 2 was 452.9.Conclusion: Ovariectomy substantially reduces the physiological fibroglandular breast enhancement. The significant decrease of the glandular breast enhancement in MRI can help to detect organic focal breast lesion, such as atypical ductal hyperplasia and to differentiate it from functional foci. The comprehension of this changes can lead to decrease the number of false positives in breast MRI interpretation.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4024.
Adjuvant UK: A UK Prognostic Model for Early Breast Cancer That Includes Mode of Detection.
Authors: Wishart G. , Azzato E. , Pharoah P. , Greenberg D. , Rashbass J. , Kearins O. , Lawrence G. , Caldas C. , Ravdin P. 
Published: December 2010

Abstract
AIM: To develop and validate a prognostication model to predict overall survival for women treated for early breast cancer in the UK based on cancer registry data. Unlike SEER, this dataset includes accurate information on mode of detection as well as systemic therapy.METHOD: Using the Eastern Cancer Registration & Information Centre (ECRIC) dataset, information was collated for 5818 women diagnosed with invasive breast cancer in East Anglia from 1999-2003. All patients underwent surgery, had records of pathological staging (tumour size, grade, lymph node status, ER status), systemic treatment (chemotherapy, hormone therapy, both), mode of detection (screen-detected, symptomatic) and follow up, censored on 31 December 2007. A model was derived from these data using Cox proportional hazards, with ER positive and ER negative tumours modelled separately, and this was subsequently validated in an external dataset of 5468 patients from the West Midlands Cancer Intelligence Unit (WMCIU). Validation was performed by comparing (a) observed and expected mortality (overall & breast cancer specific) at 5 & 8 years and (b) receiver operating characteristic (ROC) curves in both ECRIC & WMCIU datasets.RESULTS:ECRIC datasetDifference in overall observed/expected mortality &lt;1% at 5 years (14.8% vs 14.9%) and 8 years (18.9% vs 18.9%). Area under ROC curve (AUC) was 0.81.Difference in breast cancer specific observed/expected mortality &lt;1% at 5 years (10.6% vs 11.0%) and 8 years (12.9% vs 13.5%). AUC was 0.84.WMCIU dataset:Difference in overall observed/expected mortality &lt; 1% at 5 years (15.8% vs 16.5%) and 8 years (17.5% vs 17.8%). AUC was 0.79.Difference in breast cancer specific observed/expected mortality &lt;2% at 5 years (11.0% vs 12.6%) and 8 years (12.2% vs 13.6%). AUC was 0.82.Overall model fit was good across all subgroups although the ER positive model provided better discrimination (AUC 0.82) than ER negative (AUC 0.75). There was no significant difference between the ROC curves generated with ECRIC and WMCIU data (ER positive X2 = 0.17, p=0.68; ER negative X2 =0.00, P=0.95).CONCLUSION: We have developed a prognostication model for early breast cancer based on data from a UK cancer registry that has included mode of detection for the first time. The model is well calibrated, provides a high degree of discrimination and has been validated in a second patient cohort. This model will underpin a new web-based prognostication and treatment benefit tool for early breast cancer based on UK data (Adjuvant UK).
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4033.
Secreted Frizzled Receptor Protein 1 (sFRP-1) as Both a Potential Novel Biomarker of Triple Negative Breast Cancer (TNBC), and Its Sensitivity Against Taxane/Anthracycline Containing Neoadjuvant Chemotherapy.
Authors: Liedtke C. , Ruckert C. , Goette M. , von Wahlde M. , Kiesel L. , Symmans W. , Pusztai L. 
Published: December 2010

Abstract
Background: Patients with triple negative breast cancer (TNBC) carry an unfavorable prognosis despite an increased response to chemotherapy compared to other breast cancer subtypes. While tumor grade/proliferation is one major determinant of chemosensitivity in TNBC, we have recently suggested additional (molecular) features to have a significant impact as well.Material and Methods: Differential gene expression analysis was performed between TNBC (n=27) versus non-TNBC (n=106) using gene expression profiles (Affymetrix U133A) from breast cancers of patients treated with neoadjuvant taxane/anthracycline chemotherapy at MDACC (Hess et al. 2006). Differentially expressed genes were validated using profiles of 286 patients with breast cancer who did not receive systemic therapy (Wang et al. 2006). Genes were tested for (a) an association with relapse free survival, (b) an association with response to neoadjuvant chemotherapy and (c) correlation with Ki67 expression. siRNA knockdown experiments using triple negative and non-triple negative cell lines were carried out using both (a) a proliferation assay and (b) a chemosensitivity assay.Results: The secreted frizzled receptor protein 1 (sFRP-1), a member of the wnt-pathway, was identified as the top differentially overexpressed gene in TNBC (i.e. false discovery rate [FDR] &lt; 0,0001) and successfully validated in the independent dataset. In TNBC, sFRP-1 expression showed no association with relapse-free survival, but significantly correlated with an increased sensitivity to neoadjuvant chemotherapy. Importantly, it did not correlate with expression of Ki67 in TNBC. siRNA-mediated knockdown of sFRP-1 expression intriple negative MDA-MB 468 breast cancer cell lines was associated with increased proliferation and most importantly decreased sensitivity to paclitaxel in vitro.Conclusion: We suggest sFRP-1 as a novel marker of (a) the triple negative breast cancer phenotype in general and (b) its chemosensitivity to taxane-containing chemotherapy independent of Ki67 expression. Preliminary siRNA-based cell culture experiments suggest sFRP-1 to play a causal role with regard to chemosensitivity of TNBC rather than solely constituting a novel marker thereof.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4047.
The Impact of Estrogen Receptor-beta on the Actions of Endoxifen in Breast Cancer Cells.
Authors: Hawse J. , Wu X. , Subramaniam M. , Negron V. , Lingle W. , Goetz M. , Spelsberg T. , Ingle J. 
Published: December 2010

Abstract
Background: We have previously demonstrated that endoxifen is the most potent tamoxifen metabolite responsible for eliciting the anti-estrogenic effects of this drug in breast cancer cells expressing ERα (Wu, Hawse et al. Cancer Res 2009;69:1722). These studies support the clinical findings which demonstrate that women with genetically impaired CYP2D6 metabolism have significantly reduced endoxifen levels and a higher risk of breast cancer recurrence. More recently, data has emerged from several laboratories suggesting that expression of ERβ in breast tumors leads to increased benefits from tamoxifen therapy. However, the role of ERβ in mediating endoxifen action has yet to be explored.Methods: Using U2OS osteosarcoma cells, as well as Hs578T and MCF7 breast cancer cells, stably expressing ERβ, we examined the effects of endoxifen on ERβ protein levels by western blotting, ERβ transcriptional activity by real-time RT-PCR, and on ERβ inhibition of breast cancer cell growth through the use of proliferation assays.Results: We have discovered that endoxifen stabilizes ERβ protein, unlike its targeted degradation of ERα, and induces ERα/ERβ heterodimerization in a concentration dependent manner. We have also found that endoxifen is a more potent inhibitor of estrogen induced gene expression in MCF7 cells stably expressing ERβ. Concentrations of endoxifen that mimic patients with impaired CYP2D6 activity (20-40 nM) do not significantly alter E2-induced cell proliferation in MCF7 cells expressing only ERα. However, these concentrations of endoxifen significantly reduce the estrogen induced proliferation rate of MCF7 cells expressing ERβ.Conclusions: Our data demonstrate that endoxifen stabilizes ERβ protein, induces ER heterodimerization and more potently inhibits the actions of estrogen in breast cancer cells expressing ERβ. The presence of ERβ sensitizes cells to the anti-estrogenic effects of endoxifen and growth inhibition occurs at substantially lower endoxifen concentrations (20-40 nM) than in cells that express only ERα (100 nm). Our data suggest that tamoxifen therapy may be beneficial even in patients with reduced CYP2D6 metabolism when ERβ is expressed. These studies also suggest that the increased effectiveness of tamoxifen therapy in patients whose tumors express ERβ may be due to the effects of endoxifen. Finally, these findings underscore the need to further elucidate the role of ERβ in the biology and treatment of breast cancer.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 405.
The Role of the Systemic Inflammatory Response in Long Term Outcome from Operable Breast Cancer.
Authors: Henley N. , Tovey S. , Doran C. , McMillan D. 
Published: December 2010

Abstract
Aims: It is recognised that the presence of a systemic inflammatory response has independent prognostic value in a number of advanced and operable tumours. There is also evidence in advanced breast cancer (Al Murri et al., 2006). However, results in operable breast cancer have been conflicting. Therefore, we prospectively examined the relationship between the systemic inflammatory response and long term survival in primary operable breast cancer.Methods: Patients with invasive primary operable breast cancer (n=154) treated at Royal and Western Infirmaries, Glasgow between October 2000- January 2002 were studied. The systemic inflammatory response, as evidenced by elevated CRP and Il-6, was measured pre-operatively and approximately 12 months later. An elevated CRP was defined as &gt;10mg/l, and IL-6 as &gt;5ng/l. Demographic and clinical data including age, tumour size, histological grade, lymph node status oestrogen receptor (ER) status and HER2 status were recorded. The Nottingham prognostic index (NPI) was calculated and subdivided into good (0-3.4), intermediate (3.41-5.4) and poor (&gt;5.41) prognosis. Patients were followed-up until 1st March 2009.Results: Mean age was 59 (range 34-87). HER-2 was positive in 18 patients (12%), ER status was positive in 121 patients (79%). NPI was good/ intermediate/poor in 55 (36%)/ 73 (47%)/ 26 (17%). Circulating concentrations of interleukin-6 were significantly correlated with those of C-reactive protein (rs=0.449, p&lt;0.001). Median follow-up was 8 years (range 7 – 8.5 years). During this period, there were 20 breast cancer deaths and 16 of other causes. On univariate analysis, NPI (p&lt;0.001), pre-operative CRP (p=0.03), pre-operative IL-6 (p=0.05) and post-operative CRP (p=0.05) predicted breast cancer specific survival. In contrast, post-operative IL-6, ER and HER2 status did not. On multivariate analysis, NPI (HR 7.78 95% CI: 3.44-17.61 p&lt;0.001) and pre-operative CRP (HR 6.36 95% CI: 2.11-19.18, p=0.001) predicted breast cancer specific survival.Conclusions: The results of the present study suggest that the presence of a systemic inflammatory response prior to surgery, in particular CRP, predicts breast cancer specific survival independent of tumour based factors. Therefore measurement of the systemic inflammatory response may be useful in the pre-operative assessment of patients with primary operable breast cancer.We acknowledge the advice and support of Timothy G Cooke who died 20th July 2008.ReferenceAl Murri AM, Bartlett JM, Canney PA, Doughty JC, Wilson C, McMillan DC. Evaluation of an inflammation-based prognostic score (GPS) in patients with metastatic breast cancer. Br J Cancer. 2006;94:227-30.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4050.