bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P6-06-02: UGT1A1*28 and Breast Cancer: Increased Risk for Gilbert's Syndrome Patients
Authors: Francisco ARF , Gomes DBD , Souza MMT , Martini RR , Maciel GAR , Ono-Nita SK , Góes JCS , Baracat EC. 
Published: April 2011

Abstract
Introduction: Estrogens are essential for the initiation and development of breast cancer (BC). Among the enzymes involved in conjugation and inactivation of estrogens and its metabolites, there is the UDP-glucuronosyltransferase 1A1 (UGT1A1). Polymorphisms in the promoter region of the UGT1A1 gene are common in patients with Gilbert's syndrome (GS), reducing the enzyme activity by about 80%. Although considered benign, patients with Gilbert's Syndrome (GS) have lower activity of UGT1A1, which may lead to a higher risk for estrogen-dependent cancers, such as breast cancer (BC).
Methods: Case control-study and meta-analysis. Setting: academic tertiary hospital in Brazil. Cases: Women with recently operated BC, no previous neoplasm or immunossuppression. Controls: Healthy women, older than 40 years old, mammography BIRADS 1 or 2 in the last 12 months, no previous neoplasm or immunossupression. Interventions: data collection; sequencing of the UGT1A1 gene. Literature search: PubMed, EMBASE, SciElo, hand search. Languages: English, German, Spanish, Portuguese. Studies: case-control studies, BC patients and healthy subjects, genetic diagnosis of GS.
Results: From August 2008 to November 2009, 89 cases and 56 controls were enrolled. Patients were significantly older than controls (median 52 (46-64) vs 47 (43-50) y/o p=0.013), with comparable body mass index (median 27.55 vs 25.95 p=0.46), age at menarche (median 13 vs 13 p=0.68), age at menopause (median 48 vs 45, p=0.24), age at first full-term pregnancy (median 22 vs 23 p=o.46) and proportion of individuals with first degree-relatives with BC (22% vs 19%, p=0.68). The prevalence of GS was 19.1% in cases and 12.5% in controls (adjusted OR 1.65 CI95% 0.63-4.28 p=0.29), but the study was underpowered to detect differences smaller than 21%. The meta-analysis included 10 studies with 5815 BC patients and 8255 controls. There was a weak association between GS and BC (OR 1.13 CI95% 1.01-1.26 I2=2%), which was stronger for Caucasians (OR 1.14 CI95% 1.01-1,29 I2 = 20%), estrogen-receptor positive BC (OR 1.18 CI 95% 1.02-1.35 I2=0%) and individuals with a family history of BC (OR 1.4 CI95% 1.01-1.95 I2=0%).
Conclusions: In our study, the polymorphism UGT1A1 *28/*28, present in most individuals with Gilbert's syndrome, was an important risk factor for developing breast cancer. Gilbert's syndrome, usually considered benign, may be a risk factor for breast cancer. There have been no studies evaluating the incidence of BC in patients with GS. Prospective studies with patients diagnosed with SG are needed to confirm this hypothesis and assess other patients subgroups.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-06-02.
Abstract P6-08-06: C-Reactive Protein Expression and Its Association with Disease Specific Survival and Disease Recurrence in ER Negative Breast Cancer Patients
Authors: Elsberger B , Tannahill C , Orange C , Mallon EA , Wilson C , Doughty JC , Edwards J. 
Published: April 2011

Abstract
Background: The systemic inflammatory response, as evidenced by elevated serum C-reactive protein (CRP) has been reported to be predictive of poor survival, independent of tumour stage, in a variety of solid tumours (1). Previous studies suggest that systemic elevated serum CRP did not predict relapse-free, cancer-specific (DSS) nor overall survival (2). Aim of this study was to examine the relationship between expression of CRP within ER negative breast cancers and patients’ clinical outcome. Methods: Tissue microarray technology was employed to analyse tissue taken from 171 ER negative breast cancer patients at time of surgery. Immunohistochemistry was performed using an antibody to CRP. Expression was assessed using the weighted histoscore method by two independent scorers.
Results: Cohort's median age was 56 years and tumour size was 20mm, 22% were pathologically graded G2 and 74% G3 and 46% were lymph node positive. 60% underwent a mastectomy, 56% received radiotherapy and 67% chemotherapy. 33% had recurrence after a median time of 5.6 years. 47/171 patient were deceased at time of analysis. There was a definitive trend noticed between high nuclear and cytoplasmic CRP expression and DSS (p=0.078 and p=0.173, figure 1a and 1b) and recurrence (p=0.133, p=0.253, figure 2a and 2b). There was a significant association seen with high CRP expression in the surrounding tumoural stroma and DSS (p=0.007) as well as recurrence (p=0.016). Conclusion: Due to small patient numbers only trends indicating that high CRP expression within and surrounding the tumour play an important role in ER negative patients regards poorer survival and earlier recurrence. We are currently expanding our cohort further. References:
(1) Roxburgh CSD (2009). Future Oncol. 2010 Jan;6(1):149-63
(2) Al Murri AM (2007) British Journal of Cancer, 96, 891-895 Figure available in online version.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-08-06.
Abstract P6-08-08: Nucleolin as an Intracellular Transporter of Hsp72
Authors: Asea A , Pradeep A , Kaur P , Bempong P , Lillard S. 
Published: April 2011

Abstract
Background: Our previous studies demonstrated that thermal stress induces the release of Hsp72 from cells by a mechanism independent of the classical protein transport pathway. However, the exact mechanism by which Hsp72, a leaderless protein, gains access to the extracellular milieu remains unknown.
Materials and Methods: In this study we use flow cytometry to measure the expression of surface bound Hsp72 in THP1 human monocytic cells. Sucrose gradient ultracentrifugation was also used to isolate and recover intracellular fractions. Western blot analysis was used to probe for intracellular fractions expressing Hsp72, Hsp90, Grp96, CAP2, TLR2, 4, or 7. Baculovirus expression vector system (BEVS) was used to generate highly purified endotoxin free Hsp72. Plasma membrane cross-linking assay was used to identify the interacting proteins of Hsp72 on cell plasma membrane. Laser scanning confocal microscopy was used to demonstrate the plasma membrane localization and internalization of Hsp72 with other interacting proteins. In-gel digestion and LC-mass spectrometry was used to identify unique proteins colocalizing with Hsp72. Results: The data presented in this study suggest that Hsp72 trafficking within the cell and its release is assisted in part by, nucleolin. We further demonstrate that within 60 minutes after first exposure of cells to heat shock treatment, plasma membrane bound Hsp72 is internalized and redistributed into cytosolic compartments. Inhibition of active cell transport by pre-treatment of cells with Cytochalasin B completely abrogated Hsp72 redistribution from the plasma membrane into the cytosol. Cross-linking of plasma membrane bound proteins with Hsp72 followed by Western blot analysis, in-gel digestion and LC-MS/MS analysis revealed seven interacting partners with Hsp72, including Hsp90, nucleolin, gp96, CAP2, TLR2, 4 and 7. Transfection of cells with nucleolin-siRNA completely inhibited baseline and heat shock-induced Hsp72 release. Discussion: Our study for the first time demonstrates that the plasma membrane acts as a reservoir for Hsp72 and confirms that nucleolin plays an important role in Hsp72 trafficking and release.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-08-08.
Abstract P6-08-09: Leptin and Estrogen Receptor Expression in Patients Suffered with Breast Cancer and Fibroadenoma
Authors: Peredereeva EV , Lushnikova AA , Lyubchenko LN , Parokonnaya AA , Polevaya EB. 
Published: April 2011

Abstract
Introduction: Leptin is a multifunctional hormone produced by adipocytes. It plays important role in angiogenesis. Induction of cell proliferation, survival and anchorage-independent growth. These leptin activities are mediated through leptin receptor (ObR) that binds leptin molecule and stimulates Jak/STAT 3, ERK ½, cyclin D1 expression and other signal pathways. A recent data show that targeting leptin signaling may reduce mammary carcinogenesis and breast cancer (BC) progression. However, the link between obesity and leptin expression in serum/breast tumor as well as its role in modulation of estrogen receptors (EsR) and HER2/neu expression is not clear. Material and methods: We studied leptin, ObR, EsR, HER2/neu expression in patients with sporadic, familial and pregnancy-associated BC by RT PCR using BC fresh tissue and primers for genes encoding leptin, ObR, EsR-α, β. Leptin level in the patient sera was estimated also by ELISA (Leptin Sandwich DRG, DRG Diagnostics, Germany) followed by comassie staining. The data on immunohistochemical staining of HER2/neu, EsR and PrR were also obtained. In control group were patients with benign fibroadenoma (BFa) and healthy women of comparable age. Results: RT PCR results and immunohistochemistry method are mainly concordant : only 5% (5/29) of data were different. In triplonegative tumors (n=40) leptin overexpression was significantly higher than in other tumor types. Blood sera leptin level was correlates positively with ObR expression. Leptin expression in tumor tissue also correlates with HER2/neu over expression in all BC groups except triplonegative ones: Esr (-), PrR(-), HER2/neu(-). Serum leptin levels in BFa patients was higher (100-300 ng/ml) than in healthy women and the mean leptin level in BC patient of comparable age and body weight. Moreover, leptin serum level was positively correlates with ObR expression in tumors on I-III BC stages and with high body weight index (obesity). Conclusions: The data obtained indicate that leptin/ObR maight involved in BC progression. It indicates that ObR suppression isthe possible way for target BC therapy, especially of triplonegative tumors which do not express HER2/neu, so hormone therapy is not effective for these neoplasia.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-08-09.
Abstract P6-08-10: Disease Specific Survival of Breast Cancer Patients Is Not Associated with Expression of Inactive or Even Partially Activated Src Kinase
Authors: Elsberger B , Tan BA , Brown SF , Mallon EA , Edwards J. 
Published: April 2011

Abstract
Background: c-Src is implicated as a regulator of cell proliferation and survival (1). Recent work has demonstrated that c-Src and fully activated Y419Src expression in breast cancer specimens was associated with poor clinical outcome of breast cancer patients (2). c-Src is activated by a number of pathways. Known as the classical activation pathway, dephosphorylation of Y530 is needed to initiate a configuration change of the protein allowing full activation by autophosphorylation of tyrosine site 419. Phosphorylation of the tyrosine residual 530 on the c-terminal tail by Csk tyrosine kinase acts as a negative regulatory protein binding site, keeping Src kinase in a closed confirmation (3).
The aim of this translational study was to assess associations between inactivate and partially activated Src expression to clinic-pathological features of the cohort and if different stages of c-Src activation equally influences breast cancer patients’ disease specific survival. Methods: Tissue microarray technology was used to analyse tissue taken from 165 breast cancer patients taken at time of surgical resection. Immunohistochemistry was performed using anti-Clone 28 and Clone 28 antibody. To investigate those different stages of Src kinase activation, Clone 28 antibody was employed to recognise the semi-active form of Src. To evaluate protein expression of inactive Src kinase, anti-Src family negative regulatory [pY] site (anti-Clone 28= AC28) antibody was utilised for detecting phosphorylated tyrosine site 530. Expression was assessed using the weighted histoscore method by two independent scorers. Results: Using those antibodies, 50% of AC28 and Clone28 expression was observed in the nucleus and 44% AC28 and 46% Clone28 expression in the cytoplasm. Only 3.6% of AC28 was detected in the membrane, compared to Clone28 with 53% in the membrane and 55 % perinuclear. Nuclear expression of AC28 correlated negatively with ER status (chi square P&lt;0.001), whereas cytoplasmic AC28 and Clone28 correlated negatively with membrane c-Src expression (chi square p=0.008, chi square P&lt;0.001). On univariate and multivariate analysis there was no significant association noticed between AC28 and Clone28 expression and disease specific survival at any cellular location.
Conclusions: ER negative breast cancers patients were more likely to express inactive Src in the nucleus. Breast cancer patients with higher cytoplasmic expression of inactive or partially activated Src were more likely not to express c-Src at the membrane (site of activation). Inactive and partially activated Src are not associated with patients’ survival. References:
1) Frame MC. Biochim Biophys Acta 2002; 1602: 114-130.
2) Elsberger B, et. al: Am J Path (2009);175(4):1389-97.
3) Roskoski R Jr. Biochem Biophys Res Commun. 2005 May 27;331(1):1- 14.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-08-10.
Abstract P6-09-01: Breast Cancer Incidence and Hormonal Infertility Treatments: A Systematic Review of Population Studies
Authors: Gennari A , Costa M , Puntoni M , De Censi A , D'Amico M , Bruzzi P. 
Published: April 2011

Abstract
Background: With the increasing practice of hormonal infertility treatments in infertile women, both for ovulation induction in anovulatory women and for ovarian hyperstimulation in assisted reproductive technologies, concerns have been raised about the long-term effects of such practice on the subsequent risk of breast cancer. Sterility itself is an independent risk factor, though its effect is not yet clear. In the past years, a number of population-based studies has investigated the possible association between breast cancer incidence and infertility treatments, with inconsistent results. With these premises, we performed a pooled analysis of the association between infertility treatments by any kind of hormonal manipulation and breast cancer incidence, based on published data. Methods: Population cohort studies, evaluating the association between BC incidence and hormonal infertility treatments were identified by MEDLINE search. Standardised Incidence Ratios (SIRs) were pooled across the studies by inverse variance weighting. Subgroup analyses were performed according to the following covariates: lenght of follow up (&lt; 10 yrs vs ≥10 yrs), type of hormonal therapy (clomiphene vs gonadotropins) and type of control group (population based on internal control, ie infertile women). All statistical tests were two-sided. Results: Thirteen eligible cohort studies, including 364.342 women were identified and retrieved. Data on breast cancer incidence and type of fertility treatments were available for all studies. Overall hormonal infertility treatments were associated with a 15% increase in the incidence of breast cancer as compared with untreated women (SIR 1.15, CI 1.09-1.21; p &lt; 0.0001). Breast cancer risk was significantly higher in clomiphene treated women (SIR 1.21; 95%CI 1.10-1.32) than in gonadotropins users (SIR 1.04; 95%CI 0.91-1.20, p for interaction &lt; 0.05). The increase in breast cancer incidence seems to be dependent on the length of follow up (SIR 1.05; 95%CI 0.96-1.14 for &lt;10 yrs versus 1.23; 95%CI 1.16-1.31 for ≥10yrs, p for interaction = 0.03). In the subset of cohort studies using population based estimates as controls, hormonal infertility treatment was associated with an increase in breast cancer risk (SIR 1.22; 95% CI 1.15-1.30); in studies with internal controls, i.e. cohorts of untreated infertile women, a similar breast cancer risk was observed (SIR 1.03; 95%CI 0.93-1.13; p for interaction = 0.09). Conclusions: Overall hormonal infertility treatments are associated with a significant increase in breast cancer incidence. This increase is mainly observed with clomiphene administration, whereas gonadotropins seem not to affect breast cancer risk. Finally, subset analyses according to type of controls suggest that the observed increased risk may be due to the infertility condition itself.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-09-01.
Abstract P6-09-08: Patient Preference for Intra-Operative (TARGIT) or External Beam Radiotherapy Following Breast Conservation
Authors: Alvarado M , Connolly J , Oboite M , Moore D , Park C , Esserman L. 
Published: April 2011

Abstract
Background: Recently published data for the TARGIT Trial (a randomized trial comparing Intraoperative Radiotherapy [IORT] for equivalence to External Beam Radiotherapy [EBRT] following lumpectomy for invasive breast cancer for selected low risk patients) shows equivalence for the IORT and EBRT arms at 4 years follow-up[1]. The TARGIT steering committee originally used a 2.5% non-inferiority margin for statistical considerations at trial initiation. We hypothesized that patients would indeed choose IORT even with the possible 2.5% inferior local recurrence rate and can now compare recently published data to patient preference. Methods: We used a validated tradeoff technique to quantify any additional risk patients would accept to receive either treatment. Subjects who were candidates for breast conserving radiation were presented with a slideshow comparing EBRT with IORT, and then asked their preference given hypothetical recurrence risks. Two initial Tradeoff Slides were used to assess whether the initial risk comparison had an effect on patients’ switch points. The first stated both forms of radiotherapy lead to a 10% 10 year risk of local recurrence, while the second stated EBRT leads to a 10% risk versus an IORT risk of 20%. Subsequent tradeoff slides incrementally increased or decreased the rate of recurrence associated with IORT until the subject preference changed.
Results: Data from 81 patients were analyzed. The median additional accepted risk to have IORT was 2% (-9% to 39%). There were two outliers who accepted 34% and 39% additional risk with IORT. Only 7 patients chose to accept additional risk for EBRT; 22 accepted IORT at no additional risk, and the remaining 52 chose IORT with some additional risk. Patients who were grade 2 or 3 (versus 1) were more likely to accept a higher additional risk for IORT. No other factors studied correlated with a higher additional tolerated risk for IORT.
Conclusions: Some patients chose to consider IORT even if experimental and with a higher risk for 10 year local recurrence compared to EBRT. The recetly published results from the TARGIT Trial at 4 years reported a 1.2% (95%CI 0.53-2.71) local recurrence rate for TARGIT and a 0.95% (95%CI 0.39-2.3) local recurrence for EBRT, clearly within the projected margin of 2.5% inferiority. Thus, it may be appropriate to consider offering TARGIT as an informed option on registry trial to selected low-risk patients.
1. Vaidya, J et al. Targeted intraoperative radiotherapy versus whole breast radiotherapy for breast cancer (TARGIT-A trial), Lancet available online June 4, 2010
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-09-08.
Abstract P6-10-05: Bilateral Breast Cancer: A Comparative Study with Unilateral Breast Cancer
Authors: Lee Y-m , Ahn S-H 
Published: April 2011

Abstract
Background
The clinical significance of bilateral breast cancer is unclear and its influence on prognosis is controversial, whether contralateral breast cancer occurs synchronous or metachronous. Our purpose is to assess the impact of bilateral breast cancer on prognosis and compared it to unilateral breast cancer. Methods
We included 9,327 patients who diagnosed breast cancer and treated at Asan Medical Center from 1990 to 2007. Bilateral breast cancer was classified as synchronous in patients with a second breast cancer diagnosed within 6 months after the first breast cancer and as metachronous if the second breast cancer occurred more than 6 months after the first. To compare clinical features, we used more advanced-stage tumor in synchronous cases and the first tumor in metachronous cases. The follow-up cut-off date of this study was December 2009 and median value of follow-up was 59 months. This study was performed by medical records review retrospectively. Results
117 (1.3%) had synchronous breast cancer and 114 (1.2%) had metachrnous breast cancer. Except menopausal status, there were no significant differences for clinical features between the patients with unilateral breast cancer and synchronous bilateral breast cancer. Patients with bilateral metachronous breast cancer were significantly younger at the time of first diagnosis and had more often a highly increased familial risk. And women who developed metachronous cancer underwent more often mastectomy for their first tumor.
Patients with synchronous (74.2%) or metachronous bilateral breast cancer (77.7%) had the same risk of death from breast cancer as patients with unilateral breast cancer. (82.7%) (10 years overall survival, p=0.703) Also, disease-free survival was no difference between these three groups. But when we analyzed disease-free survival according to recurrence pattern, patients with metachronous breast cancer had a higher risk of loco-regional recurrence, significantly, compared with other groups. Conclusion
Patients with metachronous breast cancer developed more loco-regional recurrence than patients with unilateral disease or synchronous disease, but this recurrence didn't affect overall survival. Bilaterality of breast cancer is not associated with impaired overall survival.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-10-05.