bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epstein-Barr virus (EBV) in fine needle aspirates containing inflammatory breast cancer cells.
Authors: Li C , Pusztai L , Cohen EN , Symmans F , Wang B , Lee B , Hortobagyi GN , Cristofanilli M , Reuben JM 
Published: December 2010

Abstract
Abstract #3084
BACKGROUND: Inflammatory breast cancer (IBC) is the most aggressive manifestation of primary breast cancer and its clinical presentation and the peculiar geographic distribution have suggested a possible viral etiology. Mouse Mammary Tumor, Human Herpes Virus 8 or Epstein-Barr virus (EBV) may play significant roles in the pathogenesis of the disease and account for the peculiar lymphangiogenic mechanism of growth and disease progression. In particular, EBV late membrane protein (LMP)-1 plays a critical role in tumor invasion lymphangiogenesis. In this study, EBV DNA was measured in each FNA sample from patients with IBC and locally advanced breast cancer (LABC) using real time PCR directed against 5 different targets within the EBV genome.&#x2028; PATIENTS AND METHODS: Sixty-eight fine needle aspirates (FNA) of breast cancer from patients with newly diagnosed IBC (n=18) and LABC (n=50) were examined. The FNA specimens were collected for the pharmacogenomic research program before any systemic therapy started. Median age of subjects was 53 yrs (range: 26-83 yrs). Total DNA was extracted from the FNA using the QIAmp Kit. EBV DNA were detected by quantitative polymerase chain reaction (QPCR) directed at five different targets within the EBV genome (BamH1W, LMP1, EBNA1, LMP2, and BZLF1) that encode products that are highly conserved across all EBV strains and important for viral pathogenesis. DNA extracted from Namalwa cells were used to construct the standard (R2 = 0.993); HL60 cells were used as EBV-negative controls. Data were collected and analyzed by Sequence Detection System software (Applied Biosystems Incorporated, ABI, Foster City, CA).&#x2028; RESULTS: EBV DNA was detected in freshly obtained breast cancer FNA samples using Q-PCR. The Q-PCR assays were sensitive to as low as 1 copy of EBV DNA per reaction. Of 68 breast tumor FNA specimens, EBV genes were detected in FNA from 4/18 (22%) IBC patients (range, 1-4 genes) and 5/50 (10%) LABC patients (range, 1-3 genes). Among the 9 positive specimens, BamH1W was detected in 6; EBNA1 in 5; LMP1 in 4; BZLF1 in 2; and LMP2 in 1, respectively.&#x2028; DISCUSSION AND CONCLUSIONS: Q-PCR is an effective method for detecting EBV DNA in FNA of breast cancer patients. The two most frequently detected EBV DNA sequences were BamH1W (6 of 9) and EBNA1 (5 of 9). BamH1W is a sequence that is frequently replicated throughout the EBV genome and EBNA1 is a reliable latent gene responsible for maintaining infection for life of the host. LMP-1 is a potential viral oncogene and was detected in 4/9 patients. The detection of these EBV sequences suggest latent EBV infections in IBC and LABC patients. The clinical significance of these findings warrants further investigation.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3084.
Cytochrome P450 2D6 variants and their association with breast cancer survival.
Authors: Abraham JE , Maranian M , Driver K , Greenberg D , Shah MN , Earl HM , Dunning AM , Pharoah PP , Caldas C 
Published: December 2010

Abstract
Abstract #3089
Background: Cytochrome P450 2D6 (CYP2D6), a phase I drug metabolising enzyme, is involved in the metabolism of up to 25% of all drugs. The CYP2D6 gene is highly polymorphic with over 60 reported variant forms. Many of these have been classified by their effect on drug metaboliser status (poor, intermediate, extensive and ultra). Many variants have low minor allele frequencies (MAF) and metaboliser classification is not always certain. There is conflicting evidence for the potential predictive value of CYP2D6 genotype in patients treated with tamoxifen. In this study we investigate the association of the CYP2D6 gene variants with breast cancer survival in patients treated with tamoxifen.&#x2028; Methods: Invasive breast cancer cases (n=6510), came from SEARCH (East Anglian, UK population-based study), 3155 of these cases had received Tamoxifen therapy. CYP2D6 single nucleotide polymorphisms (SNPs) for genotyping were selected using 2 approaches: (i) Known CYP2D6 functional variants (n=13; MAF&gt;0.01), (ii) tag SNPs , that efficiently tagged all known CYP2D6 common variants on the HapMap database (n=5; MAF&gt;0.05), such that known common SNPs had an rp2 of &gt;0.8 with at least one tagSNP. (Pairwise correlation coefficient (rp2) is a measure of how well one SNP tags another.) The combination of these two approaches aims to capture all known functional variants as well as any, as yet undiscovered variants that may be tagged by the common tagSNPs. Genotyping was carried out using Taqman Assays by Design.&#x2028; Results: Preliminary results, from this ongoing study, indicate that in patients treated with tamoxifen, one rare functional variant (carrier frequency = 0.02), CYP2D6*6, is associated with decreased breast cancer survival (P=0.007; HR=2.03; 95%CI=1.21-3.40), in comparison to patients who have not received hormone therapy (P=0.359; HR=0.52; 95%CI=0.13-2.10). None of the common tagSNPs (MAF&gt;0.05) were associated with differences in survival (at P&lt;/=0.05 level).&#x2028; Conclusion: We conclude that at least one variant of the CYP2D6 gene may affect breast cancer survival in patients treated with tamoxifen. CYP2D6*6 is associated with poor metaboliser status, resulting in impaired tamoxifen metabolism. Consequently genotyping for this CYP2D6 variant may help to determine which patients are unlikely to benefit from standard tamoxifen treatment.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3089.
Gene associations and risk of breast cancer.
Authors: Andavolu RG , Cone LA , Shu S , Izsac C , Andavolu MV , Luthra M 
Published: December 2010

Abstract
Abstract #3094
Background: Human BCCIPalpha (Tok-1alpha) was identified as a BRCA2 and CDKN1A (p21, or p21(Waf1/Cip1)) Interacting Protein. BCCIP binds to a highly conserved domain proximate to the C-terminus of BRCA2 protein and the C-terminal domain of the CDK-inhibitor p21. Previous reports showed that BCCIP alpha enhances the inhibitory activity of p21 toward CDK2 and that BCCIP alpha inhibits the growth of certain tumor cells. In cancers harboring wild type p53, the p53 transactivation activity may be compromised by other mechanisms. It is clear from previous reports that BCCIP functions through p53 to regulate the expression of p21Waf1/Cip1 and BCCIPalpha is an important cofactor for BRCA2 in tumor suppression. In this study, specific SNPs in BCCIP, CDKN2A, BRCA2 and KLF6 (tumor suppressor gene) were screened to evaluate the potential influence of these genes in the predisposition to breast cancer.&#x2028; Materials & Methods: Blood was drawn from 204 primary breast cancer patients and 197 normal healthy subjects. An informed consent was obtained from all the study subjects. Genotyping was done using polymerase chain reaction followed by restriction enzyme digestion. SPSS version10.1 for windows software was used for data analysis.&#x2028; Results: A relatively high frequency of the mutant alleles showing significant association with breast cancer was observed when compared with age, gender and ethnic matched control subjects (KLF6- p&lt;0.0001; BRCA2- p&lt;0.028; CDKN2A- p&lt;0.018). Association among these gene variables were determined using spearman correlation coefficients. Significant correlations were observed among BCCIP-BRCA2 (p&lt; 0.003); BCCIP-CDKN2A (p&lt; 0.004), BRCA2-CDKN2A (p&lt;0.037) genes.&#x2028; Conclusions: Our results confirm the strong correlation of BCCIP gene with BRCA2 and CDKN2A gene. A strong association of KLF6 (tumor suppressor gene) gene with breast cancer was observed but no such correlation was identified with BCCIP, CDKN2A and/or BRCA2 suggesting that KLF6 gene may be involved in tumorigenesis using different regulating pathway. To better understand the role of these genes in the progression of breast carcinoma, gene expression studies will be performed using quantitative PCR.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3094.
Neoadjuvant trastuzumab in patients with HER2-positive locally advanced breast cancer: primary efficacy analysis of the NOAH trial.
Authors: Gianni L , Eiermann W , Semiglazov V , Manikhas G , Lluch A , Tjulandin S , Feyereislova A , Valagussa P , Baselga J 
Published: December 2010

Abstract
Abstract #31
Background: Trastuzumab (Herceptin®; H) improves survival in HER2-positive early and metastatic breast cancer. The Phase III NOAH trial is the largest neoadjuvant study that evaluated the addition of H to an anthracyclines- and taxanes-based chemotherapy (CT) for patients (pts) with HER2-positive locally advanced breast cancer (LABC).&#x2028; Methods: In this multicentre, randomised, open-label trial, women aged ≥18 years with HER2-positive (IHC 3+ or FISH+) LABC (T3N1 or T4; any T + N2 or N3 or + ipsilateral supraclavicular node involvement) were randomised to receive 3 cycles of doxorubicin (60 mg/m²) and paclitaxel (150 mg/m²) q3w, 4 cycles of paclitaxel (175 mg/m² q3w) and 3 cycles of CMF (cyclophosphamide 600 mg/m², methotrexate 40 mg/m², 5-fluorouracil 600 mg/m² q4w) on Days 1 and 8, with or without concomitant H (8 mg/kg loading dose then 6 mg/kg q3w for 1 year) before surgery. In parallel, LABC pts screened as HER2-negative (IHC 0/1+) received the same CT regimen. The primary end point was event-free survival (EFS), defined as the time between randomisation and disease recurrence or progression, or death from any cause. Secondary end points were pathological complete response (pCR), overall response rate (ORR), overall survival (OS) and safety. We report for the first time here the study's primary endpoint.&#x2028; Results: 327 pts were enrolled. Baseline characteristics were balanced for randomised pts. Inflammatory breast cancer was present in 27% of HER2-positive vs 14% of HER2-negative tumours, while 35% vs 64%, respectively, were hormone-receptor positive. EFS was analyzed after 88 events in the HER2-positive group (n=228). EFS rate at 3 years was significantly better in the H + CT arm compared with CT alone: 70.1% vs 53.3%, respectively (HR 0.56; p=0.007). EFS rate in the HER2-negative arm was 67.4%. OS data were immature at this stage. Trastuzumab treatment was the only variable significantly associated with EFS outcome in multivariate analysis which included disease stage and hormonal receptor status. Both ORR and pCR were significantly higher in the H + CT arm compared to CT alone: 89% vs 77% for ORR, respectively (p=0.02); 39% vs 20% for pCR, respectively (p=0.002). Similar results for ORR and pCR were observed between the HER2-positive CT-alone arm and the HER2-negative arm. The addition of H to CT in the neoadjuvant setting was well tolerated with acceptable cardiac safety.&#x2028; Conclusion: Neoadjuvant H significantly increased EFS in pts with HER2-positive LABC. This analysis of the NOAH study establishes neoadjuvant H with CT as a standard treatment option in women with HER2-positive LABC.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 31.
A breast international group survey of young breast cancer patients' attitudes towards the risk of loss of fertility related to adjuvant therapies. EORTC protocol 10002 – BIG 3-98.
Authors: Neskovic-Konstantinovic Z , Gomez H , Senkus-Konefka E , Dirix L , Jerusalem G , Murray E , Bottomley A , Rampion J , Duez N , Demonty G , Di Leo A 
Published: December 2010

Abstract
Abstract #3106
Objectives: Under the auspices of the Breast International Group (BIG), the European Organization for Research and Treatment of Cancer (EORTC) conducted a survey with the International Breast Cancer Study Group (IBCSG) and German Breast Group (GBG) of breast cancer (BC) patients (pts) aged 35 years or less at the moment of BC diagnosis. The primary objective of our survey was to evaluate the attitude of BC pts towards the risk of sterility related to anti-cancer treatments.&#x2028; Patients and methods: Four hundred premenopausal, early stage BC pts participated in this survey after signing the informed consent, and 389 were evaluable. Patients completed a short, previously pilot-tested questionnaire, translated into 15 languages broadly following EORTC translation procedures.&#x2028; Results: 228 pts (59%) wanted to have children in the future, but 158 (41%) did not, with 57 (36%) of these women stating they were afraid the cancer would return, and as such they would not like to have children. The wish to have children in the future was more frequently expressed by those women who had no children (84% of these pts against 43% of patients with children). Thirty-two (8%) women stated they would not undergo chemotherapy, and this was dependent on whether they already had children or not. Of the 355 pts (91%) who agreed they would have chemotherapy even knowing that this may reduce their chance of having children in the future, 113 (32%) would accept treatment even if there were only 1-5% extra chance of being cured. However, 169 (48%) would accept chemotherapy only if the extra chance of being cured exceeded 20%. Ninety-one (26%) women who would undergo chemotherapy would accept only the minimal risk of sterility of 0-25%, while 171 (48%) would accept as high as 76-100% risk of sterility. The maximum risk of sterility that would be accepted by BC patients is clearly influenced by their already having children.&#x2028; Conclusion: Our international survey provides key evidence of young, early breast cancer patients' attitudes towards infertility related to breast cancer treatments. While obviously women are primarily interested in being cured, they are also highly concerned about the loss of fertility.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3106.
Extended follow-up results from a prospective multi-center study of the impact of the 21-gene recurrence score assay on medical oncologist and patient adjuvant breast cancer treatment selection, satisfaction, and anxiety.
Authors: Lo SS , Mumby PB , Rychlik K , Smerage J , Kash J , Chew HK , Hayes D , Albain KS 
Published: December 2010

Abstract
Abstract #3113
Background: The 21-gene Recurrence Score (RS) assay has been validated to quantify the risk of distant recurrence in tamoxifen treated patients (pts) in node negative, estrogen receptor positive breast cancer (BC) and predict magnitude of chemotherapy benefit. We previously showed that the RS impacted medical oncologists (MOs) and pts adjuvant treatment decision making, decreased situational anxiety and decisional conflict, and improved pt satisfaction regarding adjuvant treatment decisions. Herein, we present the 12 month post-RS data for MOs and pts.&#x2028; Material and Methods: MOs stated their treatment recommendation and confidence in it pre- and post-RS assay, and completed a 12 month questionnaire. Pts completed 4 questionnaires pre- and immediately post-RS, and 12 months later: 1) Patient Treatment Decision Making Questionnaire; 2) Decisional Conflict Scale (DCS); 3) State-Trait Anxiety Inventory; and 4) Functional Assessment of Cancer Therapy-Breast. Frequency distributions, means and standard deviations summarized data. Paired samples t-tests and repeated measures ANOVA assessed quality of life, decisional conflict and anxiety.&#x2028; Results: Accrual goal was met with 89 evaluable pts. 16/17 (94%) MOs and 67 pts (75%) completed the 12 month assessment. There were no breast cancer recurrences recorded at 12 months. The majority of MOs reported increase confidence in their treatment recommendation (n=15, 93.8%), felt the RS provided additional information (n=15, 93.8%), and influenced treatment recommendation (n=14, 87.6%). Results from the DCS immediately post-RS indicate reduced conflict over treatment (p &lt;.0001), greater pt satisfaction, and increased confidence with choice of adjuvant therapy (p &lt;.0001). Pts reported they were glad they took the test 12 months later (n=62, 92.5%), found results easy to understand (n=60, 89.6%), and the test influenced treatment decision (n=54, 80.6%). Sixty four (95.5%) were satisfied with their adjuvant decision. State anxiety decreased over the year (mean 38.9 to 34.0, p. = 007), the most significant decline occurred pre- to immediately post-RS. Quality of life remained constant.&#x2028; Conclusions: The RS assay has an immediate and enduring impact on MOs and pts adjuvant decision making. MOs and pts report continued confidence and satisfaction with the assay. Pts had a decrease in decisional conflict right after the test, situational anxiety declined over the next 12 months and quality of life remained stable.&#x2028; Investigator initiated trial supported by an unrestricted clinical trials grant from Genomic Health Inc.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3113.
Sequencing of type I IGF receptor (IGF1R) inhibition affects chemotherapy response in vitro and in vivo.
Authors: Zeng X , Sachdev D , Zhang H , Yee D 
Published: December 2010

Abstract
Abstract #3122
Purpose: To determine the optimal sequence of combining anti-IGF1R antibodies with chemotherapeutic drugs in cancer cells in vitro and in vivo.&#x2028; Experimental design: MCF-7 and LCC6 cells were treated with sub-cytotoxic concentrations of doxorubicin (DOX) with or without anti-IGF1R antibodies (scFv-Fc or EM164 and its humanized version AVE1642). Treatments were given simultaneously, DOX followed by anti-IGF1R antibody, or anti-IGF1R antibody followed by DOX, with measurement of in vitro proliferation, apoptosis, and anchorage-independent growth. Effects of sequencing on LCC6 xenograft growth and metastasis were studied.&#x2028; Results: DOX followed by anti-IGF1R antibody (scFv-Fc or EM164) was the most effective combination strategy to inhibit cell monolayer growth and anchorage-independent growth. This sequential combination triggered increased Poly (ADP-ribose) polymerase (PARP) cleavage compared to other treatment sequences. The reverse sequence, antibody followed by DOX treatment, protected cells from chemotherapy by decreasing apoptosis, arresting cells in S phase, and inhibiting the level and activity of topoisomerase IIα . Finally, our in vivo data show that recovery of IGF1R prior to DOX therapy resulted in the best therapeutic responses. Low doses of AVE1642 that allowed IGF1R expression to recover at one week were more effective in combination with DOX than higher antibody doses.&#x2028; Conclusion: The timing of IGF1R inhibition affects responses to chemotherapy. The optimal sequence was DOX followed by anti-IGF1R antibody, while the opposite sequence inhibited DOX effects. Thus, short course suppression in combination with DOX might be the optimal combination and provides a rationale for the design of future clinical trials.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3122.
Depression-anxiety and quality of life and the use of complementary and alternative medicine among breast cancer patients in Turkey.
Authors: Kalender ME , Dirier A , Sevinc A , Camci C 
Published: December 2010

Abstract
Abstract #3130
Purpose: Breast cancer is the most common cancer type among women. The aim of this study was to examine the association between the use of complementary and alternative medicine (CAM) and quality of life, and anxiety and depression, and demographic characteristics of Anatolian women with breast cancer.&#x2028; Methods: Quality of life was measured with European Organization for Treatment and Research of Cancer (EORTC) quality of life core questionnaire (QLQ-C30, version 3.0) and anxiety and depression was measured with Hospital Anxiety and Depression Scale (HADS). The demographic characteristics of patients were filled by patient to a standard form.&#x2028; Results: Totally 122 patients with breast cancer were enrolled, and 50% (n=61) of patients reported that they were using CAM. The most commonly used CAM methods were stinging nettle (57%) and prayer and spiritual healing (49%). The statistical analysis showed that, there was a meaningful correlation between CAM usage and education level (p=0.031) and radiotherapy (p=0.002). There was no relationship between use of CAM and patients age, time since diagnosis, stage of cancer, chemotherapy using, smoking and residence. Analysis of patients showed a positive correlation between CAM and RF2 (Role Functioning) (p=0.014) and FI (Financial Difficulties) (p=0.011) and negative correlation between CAM and EF (Emotional Functioning) (p=0.033). There was no correlation between use of CAM and anxiety and depression scale. The RF2 (p=0.02), EF (p=0.047), FA (Fatigue) (p=0.038), PA (Pain) (p=0.043) and depression results (p=0.008) were better at patients with high education level. We analysed CAM using in patients living in rural or urban area, and the EF (p=0.006), CF (Cognitive Functioning) (p=0.027), PA (p=0.025), DY (Dyspnoea) (p=0.045) and DI (Diarrhoea) (p=0.000) results were better in urban area.&#x2028; Conclusions: According to the various studies in the literature, 20-83.3% of breast cancer patients were using CAM and the CAM methods are different in different countries and cultures. Our results suggest that the use of CAM among Anatolian women with breast cancer is popular. This study findings showed no correlation between anxiety and depression and CAM usage. There is a tendency to CAM usage in patients with financial problems. Emotional functioning was also worse in those patients. The study results showed that the use of CAM is more common among breast patients with bad emotional status and poor financial status.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3130.