bluuebunny/crossref_metadata_2025_split huggingface dataset:
Non-image guided fine needle aspiration of palpable axillary lymph nodes in breast cancer patients.
Authors: Marti JL , Ayo D , Levine P , Hernandez O , Rescigno J , Axelrod DM 
Published: December 2010

Abstract
Abstract #1013
Introduction&#x2028; While the utility of ultrasound-guided axillary lymph node FNA is well established, there is a paucity of data on non-image guided office-based FNA of palpable axillary lymphadenopathy. We investigate the sensitivity and specificity of non-image guided FNA of axillary lymphadenopathy in patients presenting with breast cancer, and report factors correlating with a positive FNA result.&#x2028; Methods&#x2028; Retrospective review of 80 consecutive patients who underwent office-based FNA of palpable axillary lymph nodes between 2004-2008, with cytology results compared with histology during axillary sentinel node or lymph node dissection. Pearson correlation, chi-square and Fisher exact tests were used to determine correlation with other clinical and pathologic data.&#x2028; Results&#x2028; Mean age was 56 with a median tumor size of 2.2 cm and 39% have pNO disease. Non-image guided axillary FNA was 82% sensitive, 100% specific, and 89% accurate. Positive predictive value was 100% and negative predictive value was 76%. Therefore only 24% of patients who had a negative FNA had axillary involvement compared to 61% for the entire group.&#x2028; A significant correlation or association was identified between positive FNA cytology and breast tumor size (p=0.02), number of pathologic positive lymph nodes (p&lt;0.0001), presentation with a palpable breast mass (p=0.003), radiographic lymphadenopathy (p=0.0005), lymphovascular invasion (p=0.003), stage of disease (P&lt;0.0001), and N stage (p&lt;0.0001). There was a borderline significant association with her2neu receptor status (p=0.08).&#x2028; Age, lymph node size, ER/PR status, Ki-67 index, tumor histology, multicentric disease, degree of differentiation and nuclear grade were all not significantly correlated or associated with positive FNA.&#x2028; Conclusions&#x2028; Non-image guided FNA of palpable axillary lymphadenopathy in breast cancer patients is a very sensitive and specific test. Prompt determination of lymph node positivity benefits select patients, permitting avoidance of ultrasound, sentinel lymph node biopsy, or delay in receiving neoadjuvant therapy. This results in time and cost savings for the patient and the health care system, and expedites definitive management of the patient.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1013.
Identification of BRCA1 and BRCA2 genetic modifiers.
Authors: Weyandt JD , Snyder C , Lynch HT , Gillanders E , Holmes TN , Bailey-Wilson J , Ellsworth RE 
Published: December 2010

Abstract
Abstract #1040
Background: Although mutations in BRCA1 and BRCA2 represent the primary lesions in hereditary breast and ovarian cancer (HBOC) families, these mutations are marked by incomplete penetrance, as 15-20% of carriers never develop either cancer. In addition, the expressivity of these gene mutations varies with manifestation in breast, ovary, or both breast and ovary, suggesting other genes may modify the effects of BRCA1 and BRCA2 mutations.&#x2028; Methods: DNA was isolated from nine large HBOC families with known BRCA1 and BRCA2 mutations. SNP data was generated using the GeneChip Mapping 10K Array (Affymetrix, Santa Clara, CA). The data were checked for deviation from Hardy-Weinberg equilibrium and Mendelian errors. SNPs with low completion rates were not used in the analyses. Two-point parametric linkage analysis was performed under dominant and recessive models using VITESSE and GAS.&#x2028; Results: Genotypes were generated for 301 individuals from nine families and included mutation carriers, and non-carriers with and without cancer. When all families were considered together using a dominant model, LOD scores &gt;3.0 were detected for SNPs on chromosomes 6q25.3 and 18q21.3 and &gt;2.0 for chromosomes 2q24, 5p13 and 5q33. When families were segregated by mutation type, linkage was detected at chromosome 22q12 (LOD =2.65) in BRCA1 families, and at 2q24 (LOD=2.17) in BRCA2 families.&#x2028; Conclusions: Chromosomal regions harboring putative genetic modifiers have been identified that may contribute to pathogenesis in both BRCA1 and BRCA2 families. For example, frequent gain of 2q24 has been detected in BRCA1 carriers with ovarian cancer, loss of 5q in breast tumors from BRCA1 patients, and SNP rs720321 is intragenic to the apoptosis gene BCL2 on chromosome 18q21, expression of which has been associated with BRCA2 tumors. Linkage to chromosome 22q12 was specific to BRCA1 families, of note, the loss of the CHEK2 gene, located on chromosome 22q12, may promote tumor progression in BRCA1 tumors. Further elucidation of the underlying genetic lesion from each of these chromosomal regions may improve the risk assessment and treatment regimens of women with BRCA1 and BRCA2 mutations.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1040.
Breast cancer instructs dendritic cells to express OX40 ligand and to prime pro-inflammatory type 2 CD4+ T cells that facilitate tumor development.
Authors: Palucka AK , Pedroza A , Aspord C , Gallegos M , Burton E , Banchereau J 
Published: December 2010

Abstract
Abstract #1050
We found that breast cancer tumors are infiltrated with mature dendritic cells (DCs), which cluster with CD4+ T cells. CD4+ T cells infiltrating breast cancer tumors secrete type 1 (IFN-g), pro-inflammatory (TNF) as well as high levels of type 2 (IL-4 and IL-13) cytokines. Immunofluorescence staining of tissue sections revealed intense IL-13 staining on breast cancer cells. The expression of phosphorylated STAT6 in breast cancer cells suggests that IL-13 actually delivers signals to cancer cells.&#x2028; To determine the link between breast cancer, DCs and CD4+ T cells, we implanted human breast cancer cell lines in NOD/SCID b2m-/- mice engrafted with human CD34+ hematopoietic progenitor cells (HPCs) and autologous T cells. There, CD4+ T cells promote early tumor development. This can be prevented by administration of IL-13 antagonists and is dependent on DCs. Furthermore, these humanized mice demonstrate a signature of IL-13.&#x2028; Similarly to patient samples, in humanized mice breast cancer but not melanoma tumors are infiltrated with large numbers of human myeloid DCs. DC isolated from breast tumor and its draining lymph nodes induce the production of high level of IL4, IL13 and TNF by naive CD4 T cells further demonstrating that breast tumor modulates DC to induce an inflammatory Th2 response.&#x2028; Accordingly, immunofluorescence staining of breast cancer tissue sections from patients shows high expression of OX40 ligand on DCs. This can be ascribed to activity of breast cancer cell-derived soluble factors. Finally, blocking OX40 ligand prevents generation of IL-13 secreting CD4+ T cells.&#x2028; Thus, breast cancer targets DCs to generate pro-inflammatory type 2 immunity that promotes its development.&#x2028; Supported by U19 AIO57234, RO-1 CA89440, CA78846, and CA85540.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1050.
Correlation of clinical data and expression levels of six tumor supressor genes in breast cancer.
Authors: Celebiler Cavusoglu A , Kilic Y , Saydam S , Canda T , Sevinc AI , Baskan Z , Sakizli M 
Published: December 2010

Abstract
Abstract #1058
As the scientists and physicians began to share more information for improving the personalization in medicine, we aimed to check the expression profiles for major tumor suppressor genes of 70 breast tumor samples obtained from the Dokuz Eylul Breast Tumor Biobank. We tried to figure out the levels of expressions of tumor suppressor genes by the quantity of the RNA which belongs to the examined gene in the tumor tissue samples. The expression level was measured by quantitative RT-PCR using total RNA extracted from the tissues. Fluorescence amplification plots were observed and the Ct values were used for comparing the expression levels. For quantification, we chose to normalize the Ct differences by using Genorm software with averaging four housekeeping genes (PUM1, RPL13A, ACTB, B2M). Correlation analysis is performed between genetic expression levels and the data obtained from the clinical records of the biobank.&#x2028; Although further statistical analysis is still continuing, we observed direct significant correlations between ki67 level and BRCA1 expression and between intraductal component level and CDH1 expression. Also significant relations between tubuler formation and BRCA1 expression; between intraductal component and P16 expression were observed. Dermal infiltration had significant correlatios with both TIMP3 and P16 expressions. Significant inverse correlation between estrogen receptor level and BRCA1 expression were found as well as the inverse correlation between progesteron receptor level and TIMP3 and BRCA1 expression levels. Staging had only significant correlations with TIMP3 levels.&#x2028; We also found out that expression status of BRCA1 and BRCA2; BRCA2 and CDH1; BRCA1 and GSTP1, and GSTP1 and TIMP3 shows significant correlations within themselves.&#x2028; *This study is supported by TÜBITAK, The Scientific and Technological Research Council of Turkiye.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1058.
TWIST1 and PITX2 expression in bone marrow of women with clinical stage II/III breast cancer identifies patients at risk for the development of early metastatic disease.
Authors: Dasgupta N , Watson M , Fleming T , Trinkaus K , Ferguson A , Aft R 
Published: December 2010

Abstract
Abstract #108
Background: The presence of disseminated tumor cells (DTCs) in bone marrow of women with newly diagnosed breast cancer has been associated with increased risk of recurrent disease development. We have previously described a 67-gene signature associated with the presence of DTCs using gene array analysis after immunomagnetic enrichment of these cells and found that the expression of one of the 67-genes in bone marrow of breast cancer patients, TWIST1, correlated with the development of early recurrent disease. We have now tested the remaining genes in the 67-gene signature for correlation with the development of recurrent disease. Our goal is to identify genes associated with DTCs with high metastatic potential for early detection and intervention.&#x2028; Methods: Expression of each of the 67 genes was analyzed using qRT-PCR in a breast cancer cell lines (MCF7, SKBR3, MDA/MB 231) diluted into normal human bone marrow at varying concentrations. Levels of expression in the breast cancer cells and in human bone marrow were quantitated. Genes with high expression in breast cancer cell lines and no observed expression in normal human bone marrow were further tested by qRT-PCR for expression in a validation set of bone marrows comprised of 50 specimens collected from 30 patients with clinical stage II/III breast cancer prior to any treatment. Thirteen of these patients developed recurrent disease within 16 months.&#x2028; Results: Within the 67 gene signature, 5 genes were identified that were highly expressed in breast cancer cell lines and had no detectable expression in normal human bone marrow. Expression of the 5 genes as well as keratin 19 were examined in the validation set of bone marrows. PITX2 was expressed in the bone marrow of 5 of the 13 patients who recurred within one year. Only expression of TWIST1 and PITX2 were found to correlate with the time to development of early recurrent disease (p &lt;0.0001 and 0.0002 respectively).&#x2028; Conclusion: We have found that the expression of TWIST1 and PITX2 in the bone marrow of breast cancer patients prior to any treatment identifies patients at risk of early distant disease recurrence. These genes are not expressed in normal human bone marrow. Both are transcription factors involved in the embryonic development and appear to be expressed by DTCs with high metastatic potential. Expression of TWIST1 and PITX2 may prove to be excellent markers for identifying women at high risk for distant relapse and lead to new targets for chemotherapeutic intervention.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 108.
Focal adhesion kinase overexpression in breast cancer molecular subtypes.
Authors: Melucci E , Buglioni S , Di Benedetto A , Perrone-Donnorso R , Marandino F , Antoniani B , Avetrani P , Nisticò C , Vici P , Cognetti F , Fabi A , Mottolese M 
Published: December 2010

Abstract
Abstract #1091
Focal adhesion kinase (FAK) is a protein tyrosine kinase which regulates multiple cellular processes including growth, differentiation, adhesion, motility and apoptosis and is a critical mediator of signalling events between cells and their extracellular matrix.&#x2028; FAK is highly expressed in invasive breast cancer (BC) where its upregulation has been implicated in the acquisition of an invasive tumor phenotype. Hierarchical cluster analysis identified subgroups of BC with separate gene expression profiles which detect four main tumor phenotypes, Luminal A (LA), Luminal B (LB), Basal-like (B), and HER2 subtype (HS) characterized by significant differences in prognosis. Up to now, there are no data concerning FAK distribution within the molecular BC subtypes. In this study FAK overexpression was evaluated, by immunohistochemistry (IHC), in a retrospective series of 193 invasive BC surgically treated at our Institution between 2002 and 2005. Associations with conventional pathological factors and with molecular subtypes were analyzed by Multiple Correspondence Analysis (MCA) and chi square test, aimed to determine the impact of FAK high positivity within BC molecular subtypes and to define a biologic profile associated to aggressive bio-pathologic variables such as tumor size (T), nodal status (N), grading (G), p53, Bcl2, Ki-67, p-AKT, p-MAPK . The anti-FAK 4.47 monoclonal antibody was used to detected FAK expression which was scored as high (2 or 3 intensity and ≥ 90% positive cells) or low (0 or 1 intensity and &lt; 90% positive cells).&#x2028; FAK was overexpressed in 41.7% of LA, 70% of LB, in 48.0% of HER2 subtype and 52.2% of Basal-like BC. The relationships among the bio-pathological factors, analysed by MCA, showed that FAK+ is located in the quadrant containing more aggressive tumor phenotypes such as HER2 and Basal like subtypes together with T3-4, N+, G3 and p53+, high Ki67, Bcl2–, p-MAPK+, p-AKT+. Moreover, in LA tumors, FAK overexpression is significantly related to nodal status (p=0.05), grading (p=0.007), p53 nuclear accumulation (p=0.047) and p-AKT overexpression (p=0.001) and it appears to be a useful tool in identifying BC patients at higher risk of progression.&#x2028; The presence of FAK upregulation in LA subtype, may represent a useful tool in identifying those LA patients who would benefit from more aggressive adjuvant therapy. In this context, further investigations are necessary to better assess the prognostic role of FAK overexpression in low risk BC.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1091.
Genetic counseling for BRCA1 and BRCA2 mutations in African American women.
Authors: Halbert C , Kessler L , Troxel AB , Stopfer JE , Domchek S 
Published: December 2010

Abstract
Abstract #1099
Background: Efforts are now focused on increasing access to genetic counseling and testing for BRCA1 and BRCA2 (BRCA1/2) mutations to address cancer disparities in African American women; however, limited empirical data are available on the effects of these services. Therefore, we evaluated the effects of genetic counseling among African American women at increased risk for hereditary disease.&#x2028; Materials and Methods: This study was conducted between February 2003 and November 2006. Participants were African American women (n=139) at increased risk for having a BRCA1 or BRCA2 (BRCA1/2) mutation. The effects of genetic counseling, including culturally tailored (CTGC) versus standard (SGC) counseling, on changes in risk perception and psychological functioning were evaluated.&#x2028; Results: Women who participated in genetic counseling had a significantly greater likelihood of reporting reductions in perceived risk compared to non-participants (P=0.03). Women who received BRCA1/2 results also had a significantly greater likelihood of reporting decreases in cancer worry (P=0.03). Similar effects were found among women who had a high prior probability of having a BRCA1/2 mutation (P=0.03) and those affected with cancer (P=0.04). There were no differences in CTGC and SGC in study outcomes.&#x2028; Discussion: African American women may experience some benefit from receiving BRCA1/2 test results. Participation in counseling and receiving test results may be especially beneficial to African American women who have high prior probability of having a BRCA1/2 mutation and those affected with cancer. Continued efforts should be made to increase access to genetic counseling and testing among African American women at increased risk for hereditary disease.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1099.
A gene expression signature predicts chemopreventive response of an EGFR inhibitor in a rat mammary cancer model.
Authors: Lu Y , Liu P , Wang Y , Grubbs C , Lubet R , You M 
Published: December 2010

Abstract
Abstract #1111
Rats treated with the carcinogen methylnitrosourea (MNU) develop multiple, hormonally dependent mammary tumors. The efficacy of the epidermal growth factor receptor (EGFR) inhibitor Gefitinib (Iressa) to prevent MNU-induced mammary cancers in female Sprague-Dawley rats was determined. Rats were given a single dose of MNU (75 mg/kg body weight) at 50 days of age. Rats bearing MNU-induced small palpable cancers showed variable responses to treatment with Iressa; with approximately 50% having a complete regression and the remaining 50% having a partial or no response. We conducted exon array studies of differentially expressed genes and/or alternative splicing exons related to the responses (complete vs partial or no response). Preliminary studies showed that, although there were genes whose expression was similarly modulated in both groups, a gene expression signature can be identified that is highly predictive of which rat mammary tumors are susceptible to treatment with Iressa. Cross validation results indicated that gene expression signatures may be useful in predicting the response of a rat mammary tumor to treatment with Iressa. Currently, we are conducting validation studies in a separate set of rat mammary tumors.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1111.
Prospective evaluation of neurotoxicity in breast cancer patients treated with adjuvant paclitaxel.
Authors: Crew KD , Zauderer MG , Cho C , Weimer LH , Brafman L , Fuentes D , Sierra A , Hershman DL 
Published: December 2010

Abstract
Abstract #1115
Background: Taxanes are increasingly used in the treatment of early stage breast cancer (BC). Up to 30% of patients develop moderate-severe neurotoxicity during treatment. We recently reported that about 60% of BC patients complain of some neuropathy up to 2 years after completing adjuvant paclitaxel (T) treatment. The prevalence, severity, and natural history of this syndrome have not been well described.&#x2028; Methods: Using a prospective cohort study design, women with stage I-III breast cancer undergoing adjuvant paclitaxel were enrolled. At baseline, 4 weeks, 8 weeks, 3 months, and 6 months, all patients completed the Functional Assessment of Cancer Therapy-Taxane (FACT-Tax) and quantitative sensory testing (touch perception and vibration threshold) was conducted. The FACT-Tax includes a 16-item subscale which measures the severity of neurotoxicity, where lower scores represent worsening symptoms. Blood was obtained at baseline and 2 weeks post-treatment to measure serum nerve growth factor (NGF) levels.&#x2028; Results: A total of 34 out of a target of 50 patients have been enrolled to date; median age: 48 (32-77); White/Hispanic/Black/Other: 10/17/4/1; median body mass index (kg/m2): 28 (21-44); stage I/II/III: 4/19/8; paclitaxel regimen T q2wks x4/T q2wks x6/T qwk x12: 19/8/5. Compared to baseline, there was a significant decrease in vibration sense at 8 weeks during active treatment. Mean scores on the Neurotoxicity subscale of the FACT-Tax decreased from 37.3 at baseline to 30.7 at week 4 (p=0.009) and 29.7 at week 8 (p=0.006). These scores remained lower than baseline at 3 months and 6 months after completing paclitaxel treatment (33.7 and 33.2, respectively). At 6 months, up to 50% of patients reported persistent numbness or discomfort in the hands and feet. Serum NGF analyses are underway to determine whether this biomarker correlates with neuropathy symptoms.&#x2028; Discussion: To our knowledge, this is one of the first studies to prospectively evaluate persistent neuropathy in women prior to, during and following adjuvant paclitaxel therapy. Over 50% of patients developed moderate to severe neuropathy during active treatment, which persisted 6 months post-treatment. Taxane-based chemotherapy has been shown to improve survival, however, neurotoxicity is the main long-term side effect. Understanding the natural history of this toxicity and validating appropriate measures to be used in interventions to prevent and treat taxane-induced neuropathy are critical.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1115.
Perception and measurement of strength and range of movement in women following treatment for breast cancer.
Authors: Lee M , Kilbreath SL , Beith J , Ward L , Refshauge K , Simpson JM 
Published: December 2010

Abstract
Abstract #1124
Introduction: About half the women who undergo breast cancer surgery report consequent shoulder problems. However, their perception of symptoms such as loss of movement and strength may not be reflected in physical measurements. The aim of this study was to compare the women's perception of symptoms with objective measurements of muscle strength and range of motion (ROM). Methods: One hundred thirty two women (mean age 53 years, SD 12) with early stage breast cancer participated in this study within 6 weeks of their surgery. Participants rated their perception of shoulder ROM and strength on a 5-point likert scale, with the anchors “no impairment” (0) to extreme (4). Shoulder abduction and forward flexion muscle strength were tested using a hand-held dynamometer and ROM with a digital inclinometer. Muscle weakness was defined as a deficit &gt; 20% compared to the unaffected side in either movement. Limited ROM was categorized as &gt; 20° deficit compared to the unaffected side. Results: Thirty two percent of women reported minor weakness, 17% reported moderated weakness, 4% reported major weakness, and no women reported extreme weakness. In addition, 36% reported a minor limited ROM, 32% reported moderate limited ROM, 11% reported major limited ROM, and no women reported extreme limited ROM. Fifty eight percent of women had &gt; 20% muscle weakness and 15% of women had &gt; 20° limited ROM in either shoulder flexion or abduction. There was a moderate relationship between participants' perception and objective measurements in range of motion (Spearman's rho = 0.55 and 0.57 for abduction and flexion, respectively) and a weak relationship for muscle strength (0.28 and 0.18). Interestingly, 28 women reported having no weakness on their affected side, although, strength measurements showed &gt; 20% weakness compared to the unaffected side. Also, 20 women showed less than 20% strength difference between arms but reported having minor to major loss of muscle strength. Conclusion: The women's perception was weakly related to the objective measurements. Physical and psychological factors may contribute to the perception of symptoms. Acknowledgement: Supported by NSW Cancer Council.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1124.