bluuebunny/crossref_metadata_2025_split huggingface dataset:
The sensitivity of multidisciplinary triple assessment for diagnosing breast cancer in a symptomatic breast clinic.
Authors: Britton PD , Forouhi P , O'Neill A , Wallis M , Sinnatamby R , Gaskarth M , Sue B , John BR , Wishart GC 
Published: December 2010

Abstract
Abstract #6009
Introduction: Triple assessment by a multidisciplinary team comprising clinical and radiological examination, supplemented with tissue diagnosis is the standard of care for evaluating patients with potential breast cancer in symptomatic breast clinics in the U.K. Currently there are no guidelines for acceptable sensitivity of this process. This study reports the proportion of patients who return with breast cancer after initially having been reassured and discharged (analogues to screening “interval” cancer)&#x2028; Methods: All new symptomatic episodes in the 3 year period from 01/01/2001 to 31/12/2003 were identified using a dedicated database. Patients discharged with a non-cancer diagnosis were traced through the database for a further 3 years and the clinical and imaging records of those subsequently diagnosed with cancer reviewed. Tissue diagnosis was obtained using percutaneous core biopsy in all cases.&#x2028; Results: Of the 7,740 new symptomatic patients assessed 518 (6.7%) were diagnosed with breast cancer and 7222 were discharged. Of these, 32 patients were diagnosed with breast cancer over the next 3 years (5 within 12 months, 19 within 24months). This equates to a symptomatic “interval” cancer rate of 0.6 per thousand women within 12 months, 2.5 per thousand women within 24 months and 4.1 per thousand women within 36 months. This reflects an overall sensitivity for histology-based triple assessment of 99.6%. On review a definite delay in diagnosis was found in 5 (16%, 0.6/1000), a possible delay in 9 (28%, 1.1/1000) and no delay in diagnosis (no signs of disease on original radiology and no related clinical findings) in 18 (56%).&#x2028; Conclusion: In this series less than 2 per thousand women discharged from a symptomatic clinic were subsequently found to have a cancer that might have been diagnosed at initial assessment, with an overall sensitivity for triple assessment of 99.6%. Modern multi-disciplinary “triple” assessment is a safe method of evaluating patients with potential breast cancer.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6009.
Increase in mastectomies performed in patients in the community settings undergoing MRI.
Authors: Ayoola AG , Alagarsamy S , Jaboin J , Rao S 
Published: December 2010

Abstract
Abstract #6010
Background: It is estimated that about 182,460 new cases of breast cancer will be diagnosed in 2008 with an estimated 40,500 deaths. Contrast-enhanced MRI has been shown to have a high sensitivity for the detection of breast cancer in high-risk women with variable specificity. MRI offers an advantage that it is less operator dependent and can demonstrate small cancers, ductal carcinoma in-situ (DCIS), and multifocal disease effectively. The role of MRI in average-risk women however is not well elucidated. In these patients, MRI detects more lesions than mammography but it is uncertain if these lesions have significant pathologic potential or if the use MRI alters the ultimate surgical intervention in these patients.&#x2028; Material and Methods:This is a retrospective study of 178 female patients over the age of 18 with breast carcinoma who underwent mammogram and MRI between January 2000 and December 2005. The patients' records were obtained from physician offices affiliated with three community hospitals in Baltimore, Maryland. The radiological and pathological reports of these patients were also examined.Of the 178 charts screened, 18 patients were excluded in the analysis because of missing data.&#x2028; Results: MRI detected more lesions than mammogram; however, these lesions were not cancerous. The lesions detected by mammogram correlated more with pathological lesions. MRI detected more lesions as compared to the pathological specimens.&#x2028; &#x2028; More patients who had both imaging modalities underwent mastectomies compared to those who had mammogram alone.&#x2028; &#x2028; Discussion: The ability of MRI to detect an increased number of truly pathologic lesions has been a matter of controversy. In our patient pool, we demonstrated that MRI lesions did not correlate significantly with the number of pathological lesions found in subsequent surgical specimens. These findings suggest that MRI has a high sensitivity and low specificity in the detection of pathologic lesions in our study population. Based on this data, we can hypothesize that the use of MR imaging resulted in a higher number of lesions necessitating conversion to a mastectomy over treatment with lumpectomy alone.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6010.
Prevalence of BRCA1 and BRCA2 genes mutations in a sample of families with high risk of breast and ovarian cancer in Brazil.
Authors: Esteves VF , Thuler LS , Amendola L , Frankel PP , Vieira RJ , Koifman RJ , Koifman S 
Published: December 2010

Abstract
Abstract #6020
Introduction: Of all malignant neoplasia among women, breast cancer has the highest incidence rate in Brazil. The objective of the present study was to ascertain the frequency of genetic modifications in a high risk population for breast and ovarian cancer from different regions of Brazil. Methods: An exploratory, descriptive study was carried out on the prevalence of the BRCA1 and BRCA2 mutations in case series of high risk families to breast and/or ovarian cancer. Following the respective heredogram construction, a sample of blood was taken and DNA extraction was performed to all index cases. The protein truncation test (PTT) was used to screen for truncated mutations in exon 11 of the BRCA1 gene and in exons 10 and 11 of the BRCA2 gene. Results: Of the 612 individuals submitted to genetic testing, 21 (3.4%), 19 women and 2 men, had mutations in the BRCA1 or BRCA2 genes. BRCA1 mutations consisted of ins6kb, 5382insC, 2156delGinsCC, 185delAG, C1201G, C3522T and 3450del4 mutations, while BRCA2 mutations were 5878del10, 5036delA and 4232insA. Conclusion: The prevalence of germline mutations in the BRCA1 and BRCA2 genes found in the present study was lower than reported by other studies in Brazil. The inclusion of individuals with medium risk may have contributed towards the lower observed prevalence. Nevertheless, individuals with a high probability of carrying mutations should be advised with respect to the possibility of undergoing genetic testing, and of the risks, benefits and limitations of these tests.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6020.
Obesity, insulin resistance and oxidative stress: implication for breast carcinogenesis.
Authors: Lewis CM , Bu D , Euhus DM 
Published: December 2010

Abstract
Abstract #6025
Background: Obesity is associated with a modest increase in the risk of postmenopausal breast cancer (RR = 1.5 – 2.0); but, because nearly a third of the U.S. population is obese, the population attributable risk is estimated at 15%. Obesity can cause insulin resistance culminating in Type II diabetes. Notably, breast cancer incidence is significantly increased in the years preceding a diagnosis of type II diabetes. Because IGFBP-1 expression is tightly regulated by insulin, it is an excellent marker of insulin resistance in healthy individuals.&#x2028; Methods: These data are based on well-annotated prospectively acquired baseline blood and breast tissue samples from 72 high risk women between the ages of 37 and 86 years who participated in a chemoprevention trial. None of the women had been diagnosed with Type II diabetes. Women with plasma IGFBP1 levels in the lowest tertile (mean 2.1 ng/ml) were classified as insulin-resistant.&#x2028; Results: Plasma IGFBP1 was strongly inversely correlated with BMI (R2 = 0.247, P &lt; 0.0001). Insulin-resistant women had marginally higher mean plasma free estradiol levels than women not classified as insulin-resistant (2.13 x 10-12M versus 1.53 x 10-12M, P = 0.072). There was no difference in plasma IGF1, IGF2, or IGFBP3 levels. Illumina whole genome expression microarray data was available for breast tissue from 55 women. Women classified as insulin-resistant showed evidence of an adaptive response to oxidative stress based on significant upregulation of NQO1, GSTK1, CYP4ZP2, and SRXN1 (P &lt; 0.001).&#x2028; Conclusions: Marginally increased circulating estradiol may contribute to the increased breast cancer risk observed in insulin-resistant women. However, insulin resistance increases oxidative stress in breast tissue and may promote carcinogenesis through induction of oxidative DNA damage.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6025.
Relationships between estrogen receptor co-regulators and intrinsic subtypes in breast cancer.
Authors: McCafferty MP , McNeill RE , Miller N , Kerin MJ 
Published: December 2010

Abstract
Abstract #603
Background: Gene expression profiling has characterised breast cancers into distinct subtypes largely based on the ER, PR and HER2/neu receptor status (i.e., luminal A, luminal B, HER2/neu over-expressing and basal-like groups). This study aims to investigate relationships between expression levels of genes representing these receptors i.e., ESR1, ESR2, PGR and ERBB2, and selected estrogen receptor co-activator genes (NCOA3, CREBBP) and co-repressor genes (NCOR1 and NCOR2). We also sought to identify whether these co-regulator genes were differentially expressed across subtype, related to patient outcome or known prognostic factors.&#x2028; Materials and Methods: Using quantitative real-time PCR, we measured mRNA expression in sixty primary breast tumors and ten normal mammary glands. Relationships between gene expression levels and clinicopathological parameters, intrinsic subtype and clinical outcomes were analysed using Pearson's correlation coefficient, student t-test, ANOVA, Kaplan-Meier survival curves and Cox's proportional hazards model. P&lt;0.05 was considered significant.&#x2028; Results: Statistically significant correlations were observed between CREBBP expression and ESR1 (r =0.324); ESR2 (r=0.387); PGR (r=0.397); and ERBB2 (r=0.306). CREBBP also correlated with NCOA3 (r=0.447), a steroid receptor co-activator previously shown to be over-expressed in breast cancers; and was differentially expressed in the luminal B subtype compared to the others (P&lt;0.001). An increase in tumour stage and NCOA3 expression was associated with shorter overall survival (Log Rank; P=0.009 and P=0.043). Prognostic significance of these parameters remained after multivariate analysis. We found no correlation between co-regulator expression and age at diagnosis, macroscopic tumour size and lymph node status.&#x2028; Discussion: These findings demonstrate a relationship between CREBBP, breast cancer subtype, and the expression of genes known to be prognostic indicators or indicators of treatment response in breast cancer. Further investigations are required to establish how co-regulator expression influences these intrinsic groups.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 603.
mTOR modulates cellular fat metabolism by regulating stearoyl-CoA desaturase 1 transcription.
Authors: Luyimbazi D , Akcakanat A , Zhang L , Zheng Y , Meric-Bernstam F 
Published: December 2010

Abstract
Abstract #6030
mTOR (mammalian target of rapamycin) signaling is a central regulator of cell growth and proliferation. Rapamycin and its analogues have been shown to inhibit breast cancer cell growth in preclinical models, and are actively being pursued in clinical trials. We performed a high-throughput microarray polysome analysis to identify novel genes whose expression was regulated by rapamycin at the level of transcription or translation. In three breast cancer cell lines representing different breast cancer subtypes, we found a significant decline in polysome-associated mRNA for stearoyl-CoA desaturase 1 (SCD1), the rate-limiting enzyme in monounsaturated fatty acid synthesis. Insulin and insulin-like growth factor, both activators of mTOR, increase SCD1 expression. Rapamycin and PI3K inhibitors decrease SCD1 protein, as does mTOR siRNA. Quantitative RT-PCR of total, polysomal and monosomal RNA, northern analysis and stability studies demonstrate that rapamycin regulates SCD1 at the level of transcription. Furthermore, rapamycin inhibits the SCD1 promoter activation by mevinolin, an inhibitor of cholesterol biosynthesis. We demonstrate that mTOR regulates SCD1 expression. This establishes a novel link between cell signaling and cancer cell fat metabolism. In doing so, we also present SCD1 as a potential marker of response to treatment by mTOR inhibitors.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6030.
Lack of TIMP-1 tumor cell immunoreactivity predicts effect of adjuvant anthracycline based chemotherapy in patients (n=647) with primary breast cancer.
Authors: Willemoe GL , Hertel PB , Bartels A , Jensen M , Balslev E , Mouridsen H , Ejlertsen B , Brünner N 
Published: December 2010

Abstract
Abstract #6042
Background: Randomized trials have in general demonstrated that anthracycline-based chemotherapy prolongs disease-free and overall survival as compared to CMF-based regimens. In the Danish Breast Cancer Cooperative Group (DBCG) 89D randomised trial a 21% improvement in overall survival was observed from substitution of methotrexate in the CMF combination with epirubicin. This suggests that the additional effect of anthracyclines is confined to a subset of the patients. We have previously shown that in vitro grown cancer cells devoid of Tissue Inhibitor of Metalloproteinases-1 (TIMP-1) are more sensitive towards chemotherapy than cells expressing TIMP-1 (Davidsen et al., Br J Cancer, 2005). In addition, we have recently published (Schrohl et al., Clin Cancer Res., 2006), that patients with metastatic breast cancer and high levels of TIMP-1 in their primary tumor tissues, have a significantly reduced likelihood of obtaining an objective response to chemotherapy.&#x2028; Purpose: The aim of the present study was to evaluate if Tissue Inhibitor of Metalloproteinses-1 (TIMP-1) tumor cell immunoreactivity could be used to identify a subset of patients who benefits from adjuvant chemotherapy.&#x2028; Patients and Methods: Formalin fixed paraffin embedded tissue micro arrays from 647 patients who were enrolled in the Danish Breast Cancer Cooperative Group randomized trial 89D comparing adjuvant CMF versus adjuvant CEF were analysed for tumor cell TIMP-1 immunoreactivity. The primary end-point was invasive disease free survival (IDFS). Immunohistochemistry was performed using the anti-TIMP-1 monoclonal antibody VT7 as described previously (Sørensen et al., J. Hist. Cytochem., 2006) and the slides were scored as + or – for positive immunoreactivity.&#x2028; Results: Tumor cell TIMP-1 immunoreactivity was found in 75% of the tumor samples. In the CEF treated patients, individuals with TIMP-1 negative tumors had a significant longer IDFS than patients with TIMP-1 positive tumors (p=0.047). The multivariate Cox regression analysis of IDFS showed that CEF was superior to CMF among patients with TIMP-1 negative tumors (HR: 0.51; 95%CI: 0.31 to 0.84, p=0.008), while no significant difference could be demonstrated among patients with TIMP-1 positive tumors (HR: 0.86; 95%CI: 0.66 to 1.11, p=0.24). However, only a non-significanct trend could be demonstrated between TIMP-1 status and CEF versus CMF (p=0.07 for interaction).&#x2028; Conclusion: Lack of TIMP-1 tumor cell immunoreactivity seems to predict a favourable effect of epirubicin containing adjuvant therapy in primary breast cancer. However, an independent study is awaited to validate the potential predictive value of TIMP-1 immunoreactivity.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6042.
Diffuse optical spectroscopic imaging measures tumor functional response to bevacizumab: initial studies.
Authors: Tanamai W , Cerussi AE , Mehta R , Hsiang D , Tromberg BJ 
Published: December 2010

Abstract
Abstract #6056
Background: Diffuse Optical Spectroscopic Imaging (DOSI) is a non-invasive, bedside functional imaging technique that quantifies the concentrations and molecular states of tissue hemoglobin, water, and lipids. Pilot studies have shown that DOSI may be a useful tool for quantifying neoadjuvant chemotherapy response, typically by comparing the degree of change in tumor water and deoxy-hemoglobin concentrations before and after therapy. DOSI may offer a point-of-care measurement of tumor responses to therapeutic intervention. The majority of these DOSI studies have measured responses to Anthracyclines. However, the optical response to Bevacizumab has not been demonstrated in vivo in human subjects.&#x2028; Materials and Methods: Twenty-one patients diagnosed with stage II/III cancers were followed with DOSI prior to and during their two-stage neoadjuvant chemotherapy regimen that featured (a) Anthracyclines (2-4 cycles) and (b) Trastuzumab/Bevacizumab (for HER2+/HER2- status, respectively). Changes between pre-treatment and pre-surgical DOSI-measured parameters were compared against final surgical pathology (complete, partial, or non-responder). A functional tissue optical index (TOI) was calculated that has been shown to discriminate between normal and malignant tissues.&#x2028; Results: Both short-term and long-term changes in tumor physiology were observed. For both therapy strategies (N=21), statistically significant changes were measured in TOI from baseline to pre-surgery between complete (95+/-15%), partial (79+/-11%) and non-responders (38+/-42%). TOI changes after the initial therapy stage were strongest in patients with more favorable pathological responses (78%, 56%, and 12% for complete, partial, and non-responders respectively). For patients receiving Bevacizumab (N=9), more detailed serial image analysis of tumor deoxy-hemoglobin revealed short-term changes (7-14 days) where initial decreases in hemoglobin were soon followed by slow increases back to pre-treatment levels. Two of the patients who received Bevacizumab demonstrated detectible residual disease by DOSI after completion of all neoadjuvant therapy, despite that contrast-enhanced MRI signals had disappeared.&#x2028; Discussion: We have provided evidence that DOSI may be well-suited to monitor the response of different cancer drugs, including anti-angiogenic compounds such as Bevacizumab, in breast cancer patients. While the usage of Bevacizumab in human subjects is still under investigation in breast cancer, we foresee that DOSI may be a useful tool in general for the development of drugs and dosing strategies.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6056.
Validation of the predictive value of tissue inhibitor of metalloproteinases-1 for the response to first-line chemotherapy in metastatic breast cancer.
Authors: Würtz S[ , Klintman M , Christensen IJ , Hertel PB , Fernø M , Malmberg M , Mouridsen H , Cold F , Schrohl A , Foekens JA , Malmström P , Brünner N 
Published: December 2010

Abstract
Abstract #6057
*Würtz SØ and Klintman M contributed equally, Malström P and Brünner N shares the senior authorship.&#x2028; Background. Predictive markers are scarcely represented in breast cancer. TIMP-1 has in a previous study (n = 173) performed in our laboratory been shown to carry predictive information for the response to chemotherapy in metastatic breast cancer as high tumor tissue levels of TIMP-1 were significantly associated with a low objective response rate to treatment with the most frequently used chemotherapeutic drugs (CMF or anthracyclines). The purpose of the present study was to validate these previous results with a new independent patient population.&#x2028; Methods. The TIMP-1 level was measured using a validated ELISA in 168 primary tumor extracts from patients with metastatic breast cancer and levels were associated with the objective response to CMF and anthracyclines. Patients were included in the study provided that they had received chemotherapy for their metastatic disease and that frozen tumor tissue as well as data on their objective response to chemotherapy was available.&#x2028; Results. The median TIMP-1 level in responders was 17.3 (2.9 – 75.8) ng TIMP-1/mg protein and in non-responders it was 19.6 (0-190.3) ng TIMP-1/mg protein. When analysed as a continuous log-transformed variable, increasing tumor levels of TIMP-1 were associated with a decreasing probability of objective response to CMF or anthracyclines (OR = 1.59, 95% CI: 0.97 – 2.62, p = 0.07). This is very similar to the original study and thus supporting previous data. Next, we used a more clinically relevant approach for analysing the data from the validation study. For this analysis, objective response was scored as complete or partial response versus stable disease lasting at least six months (clinical benefit) versus progressive disease (non-response). This analysis showed that increasing levels of TIMP-1 were associated with a poor clinical benefit rate from chemotherapy (OR = 1.56, 95% CI: 0.98 - 2.51, p=0.06). The original study has not previously been analysed using this endpoint. When performing this analysis, similar results were found (OR = 1.62, 95% CI: 1.06 - 2.48, p = 0.02). Combining the new population and the original population in a pooled analysis (n = 341) using a random effects model showed that high levels of TIMP-1 were highly significantly associated with a poor clinical benefit rate from chemotherapy compared with patients with low levels (OR = 1.59, 95% CI: 1.16 - 2.18, p=0.003).&#x2028; Conclusion. The present validation study supports previous findings that primary tumor tissue levels of TIMP-1 carries predictive information in metastatic breast cancer treated with chemotherapy.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6057.