bluuebunny/crossref_metadata_2025_split huggingface dataset:
OT2-01-04: Cardiac Safety of Anthracycline-Containing Adjuvant Chemotherapy of Early Breast Cancer: OSCAR/ABC Ongoing, Observational, Multicentric Study.
Authors: Ricevuto E , Cocciolone V , Zilli M , Scognamiglio MT , Pistilli B , Di Menna G , Mancini M , Cannita K , Adinolfi MI , Ferrandina MG , Pancotti A , Recchia F , Latini L , Ficorella C , Iacobelli S 
Published: June 2012

Abstract
BACKGROUND: Among the different chemotherapeutic options available for adjuvant treatment of early breast cancer (EBC), anthracycline-containing regimens represent prevalent choices. OSCAR/ABC is an observational, prospectic, multicentric study aimed at evaluating, in the clinical practice, the relevance of cardiac dysfunction and congestive heart failure (CHF) associated to “free choice”, anthracycline-containing adjuvant regimens and to identify patients at increased cardiac risk. PATIENTS AND METHODS: patients candidate to receive adjuvant anthracycline-containing chemotherapy, will be enrolled in the study. Data on demographic and clinical characteristics of patients (age, cardio-vascular comorbidity) tumor features (TNM, histotype, ER and PgR status, Ki67, and HER2 status), type of adjuvant regimen and tolerability of treatment will be collected and centrally registered at the Consorzio Interuniversitario Nazionale per ***1a Bio-Oncologia (CINBO) using e-CRFs. Data on type, sites and doses of radiotherapy performed will be collected, to evaluate the possible impact on cardiac function. Primary aim of the study is to evaluate the prevalence of cardiac dysfunction and CHF among the whole population enrolled, particularly according to risk criteria and type of administered chemotherapy. Cardiac dysfunction is defined as limiting cardio-vascular toxicity (≥ Grade 3 dyspnea, arrhytmia, hypertension) and/or asymptomatic LVEF reduction ≥20% (if &gt;50% at the baseline) or ≥10% (if ≤50% at baseline); CHF is defined as clinical diagnosis and/or symptomatic LVEF reduction ≥20% (if &gt;50% at the baseline) or ≥10% (if ≤50% at baseline). Assessment of cardiac risk involves the evaluation of age (&lt; vs ≥ 65 years), cardio-vascular comorbidities (requiring treatment or not) and Left-Ventricular Ejection Fraction LVEF (&gt; vs ≤ 55%) at diagnosis. Clinical and instrumental cardiac evaluation (ECG, Ecocardiography) will be performed at study entry, on-treatment and up to 5 years thereafter. Secondary objective of the study is to evaluate the clinical properness of different adjuvant anthracyclines-containing chemotherapy options, with regard to prevalence of therapeutic regimens, safety, efficacy (DFS and OS) and costs analysis. Cardiac safety and general toxicity on-treatment will be evaluated according to NCI criteria. The expected enrollment is 1,200 patients in 36 months. From September 2010 to May 2011, 7 of the 13 Centers involved in the study are active, with 65 enrolled patients.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr OT2-01-04.
OT2-04-01: A Randomized Phase II Trial of Vitamin D vs Placebo in Premenopausal Women: CALGB 70806.
Authors: Wood ME , Kingsley F , Ambaye AB , Yee L , Jung S-H , Marshall JR , Paskett E 
Published: June 2012

Abstract
Background
Chemoprevention studies are long and expensive. Gaining information about the feasibility of an agent using biomarker endpoints can save money and ensure that only the most promising agents move forward. There is strong evidence to suggest breast cancer prevention properties for vitamin D. The safety and tolerability of this agent makes it a perfect candidate for a chemopreventive agent. This clinical trial will evaluate the effect of vitamin d on several breast cancer; providing important information regarding the feasibility of a larger chemoprevention study using cancer development as the endpoint. Successful completion of this study will also validate this design of biomarker testing of potential chemoprevention agents within a cooperative group setting and add to data validating these specific biomarkers.
Methods: This is a randomized placebo controlled trial of one year of 2000 units of vitamin D (cholecalciferol) for premenopausal women (≥ 35 years) with increased breast density. The primary aim of this study is to evaluate the effect of vitamin D on breast density. Secondary aims include evaluation of vitamin D effects on IGF1 and markers of cellular proliferation (Ki-67 and atypia). In addition 3 methods of density analysis (Breast Imaging Reporting and Data System (BI-RADS), Visual Analogue Scale (VAS), and the Boyd method) will be compared. For the primary endpoint of change in mammographic density we will have an 87% power to detect a standardized effect size (difference in means divided by standard deviation) of 0.4 in change of mammographic density between two arms. The target effect size is 2.64%.This study was activated 10/15/2010 and has been opened at 75 sites with 15 patients enrolled. Target accrual is 250.
Funding: This study is sponsored by the NCI and CALGB.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr OT2-04-01.
OT2-04-02: Metformin for Breast Cancer Prevention: A Pilot Study.
Authors: Ledgerwood MM , Ojeda-Fournier H , Patterson R , Hasteh F , Andre MP , Cadmus L , Blair S 
Published: June 2012

Abstract
Background
There is a body of accumulating evidence connecting metformin, a biguanide derivative which reduces hepatic gluconeogensis and improves skeletal muscle insulin sensitivity, to reduced breast cancer risk. This, in addition to a well established drug safety record among diabetics and non-diabetics, has provoked an interest in further study of metformin's effects on breast cancer risk indicators. In our study, we examine the effects of metformin on breast density and proliferative cell marker Ki67, both indicators of breast cancer risk. This is a small observational pilot study to determine the feasibility of subject recruitment, data collection through fine-needle aspiration, and breast density measurement.
Trial Design: Recruitment of 10 breast surgery patients with high risk histology to: 1. Undergo peri-areolar fine needle aspiration (RPFNA) used to collect breast cells for analysis of proliferative marker Ki67. 2. Breast density assessment by a) mammography (the standard method) and b) whole-breast ultrasound (an innovative method recently developed at UCSD).
Each subject will undergo a single view mammogram, whole-breast ultrasound, and intra-operative RPFNA. No drug or therapeutic intervention will take place in this pilot study.
Eligibility: Female undergoing excisional high risk breast surgery.
Specific Aims: Aim 1. To determine the feasibility of recruiting high risk breast surgery patients to an observational study involving RPFNA, mammography, and whole-breast ultrasound.
Aim 2. a) To compare mammography and whole-breast ultrasound for measurement of breast density. b) To examine potential for detecting biomarkers of cell proliferation through RPFNA.
Statistical Method: Breast density will be determined by the ratio of fibroglandular tissue to fat measured on mammogram and WBU. Cell proliferation will be assessed by the percentage of positivity for biomarker Ki67 in breast ductal cells.
Accrual and target accrual: Five of ten breast excisional high risk breast surgery subjects have been accrued at this time.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr OT2-04-02.
OT2-07-01: Pasireotide Long Acting Release (LAR) in Breast Cancer Patients To Prevent Lymphocele after Mastectomy and Axillary Node Dissection: A Randomized, Multicenter, Phase II Study.
Authors: Chereau E , Uzan C , Bezu C , Mazouni C , Ballester M , Gouy S , Rimareix F , Garbay J-R , Daraï E , Uzan S , Coutant C , Rouzier R 
Published: June 2012

Abstract
Background: Lymphocele is the principal post-operative morbidity following axillary node dissection. According to the literature, incidence can vary from 4 to 89%.
Encouraging results in terms of reducing postoperative lymphoceles as well as drainage duration and volume using octreotide have been recorded recently. A new molecule, namely pasireotide, developed by Novartis Pharma AG, Basle Switzerland, is a somatostatin analog possessing high binding affinity to 4 of the 5 somatostatin receptors. Trial design: We are performing a prospective, randomized 1:1, double blind, multicenter trial against placebo with a Bayesian design.
Eligibility criteria: any female patient scheduled for breast surgery with mastectomy and axillary node dissection indicated at the pre-surgical stage.
Specific aims: The purpose of this trial is to assess the efficacy of a single pre-surgical injection of pasireotide LAR 60 mg im in reducing the postoperative incidence of symptomatic lymphoceles following mastectomy with axillary node dissection for breast cancer. Patients are followed up for 4 weeks
Statistical methods: The statistical analysis will be carried out sequentially after observing the principal criterion (i.e. success is defined as a total volume of lymphocele following single or repeated aspiration ≤ 60 cc in the 28 days following surgery or a routine aspiration volume on the 28th day ≤ 120cc) of each patient included for each randomization group, with or without treatment.
It involves estimating the probability of a response in each group using a Bayesian design based on a beta-binomial model. With the Bayesian approach, the response rate in each group (πi) is considered as a random variable, with a priori density focused on the anticipated response rate of 80% in the group receiving treatment and 60% in the non-treatment group, which will be sequentially updated as the observations are made according to a so-called a posteriori law. Present accrual and target accrual: The sample size consists of a total of 90 patients with 45 patients in the active treatment group and 45 patients in the placebo one. To date more than 50% of the patients have been included.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr OT2-07-01.
OT3-01-15: Phase III Trial Evaluating the Addition of Bevacizumab to Endocrine Therapy as First-Line Treatment for Advanced Breast Cancer: The LEA Study.
Authors: De la Haba-Rodriguez JR , von Minckwitz G , Martín M , Morales S , Crespo C , Guerrero A , Anton-Torres A , Gil M , Muñoz M , Carrasco E , Rodríguez-Martin C , Porras I , Aktas B , Schoenegg W , Tio J , Mehta K , Loibl S , On Behalf of GEICAM and GBG 
Published: June 2012

Abstract
Background
Retrospective clinical data suggest that high vascular endothelial growth factor (VEGF) levels in breast tumors are associated with a decreased response to endocrine therapy. We designed the randomized phase III LEA study of first-line bevacizumab in combination with endocrine therapy, to address the hypothesis that anti-VEGF treatment can prevent resistance to endocrine therapy in patients with advanced breast cancer sensitive to such treatment.
Methods: Postmenopausal patients with evaluable locally recurrent or metastatic breast cancer, HER2−negative- and estrogen receptor (ER)-and/or progesterone receptor (PgR)-positive disease, and eligible to receive hormonal treatment are candidates for this study. Patients are randomized to receive letrozole 2.5mg daily or fulvestrant, 250mg every 4 weeks (Arm A) or the same hormonal therapy plus bevacizumab 15mg/kg every 3 weeks (Arm B). The primary objective is to compare progression-free survival (PFS) between the treatment arms. Secondary endpoints are overall survival, time to treatment failure, overall response rate, response duration, clinical benefit rate and safety. In total, 344 patients (172 in each treatment arm) will be needed to detect a hazard ratio of 0.69 (corresponding to a median PFS of 9 months in Arm A and 13 months in Arm B) with a power of 80% and a two-tailed log-rank test at 0.05. With an expected drop-out rate of 10%, 378 patients will be included. Efficacy analysis will be triggered after 270 events.
Results: Recruitment began in November 2007. To date, 348 patients have been included in the study in Spain (n=244) and Germany (n=104). We anticipate completing recruitment by September 2011. Baseline characteristics of the first 334 randomized patients are shown in the table.

Conclusions: LEA is the first study to explore the use of an anti-angiogenic drug in combination with endocrine therapy in the context of a phase III study.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr OT3-01-15.
OT3-01-16: A Phase 2 Study of Ridaforolimus (RIDA) and Dalotuzumab (DALO) in Estrogen Receptor Positive (ER+) Breast Cancer.
Authors: Lu BD , Blum JL , Cortes J , Rugo HS , Swanton C , Eaton L , Song Y , Zhang T , Ebbinghaus SW , Baselga J 
Published: June 2012

Abstract
Background: Activation of the PI3K/AKT/mTOR pathway is common in breast cancer. Preclinical studies indicate that the dual inhibition of IGFR and mTOR may be additive or synergistic and abrogates the feedback activation of AKT due to rapamycin analog mTOR inhibitors. A phase 1 study of the mTOR inhibitor RIDA and the anti-IGFR antibody DALO demonstrated that the combination was feasible and well-tolerated at doses that were nearly those used for the two single agents and with dose limiting toxicity of stomatitis, similar to RIDA as monotherapy. A preliminary signal of anti-tumor activity, including partial responses and prolonged progression free survival, was observed in ER+ breast cancer, especially in high proliferation tumors. This observation is supported by data from tumor profiling and preclinical data suggesting that ER+ high proliferation breast cancer may be responsive to the RIDA-DALO combination. Methods: This is a two-part, adaptive design study intended to first test the combination of RIDA-DALO against a standard agent, exemestane, for ER+ positive breast cancer that has progressed after aromatase inhibitors. The trial is a multi-center, international, randomized study with PFS as the primary endpoint. Patients (pts) are stratified into high and low proliferation strata based on baseline Ki67, and the low proliferation stratum is capped to ensure adequate enrollment of high proliferation pts. If Part A shows a PFS benefit for RIDA-DALO, Part B is intended to show the PFS benefit of the combination over the single agents by comparing RIDA-DALO to RIDA and DALO. Part B will be further adapted based on whether the PFS benefit in Part A is observed in all-comers or the high proliferation subset. Tumor tissue is collected for molecular profiling and analysis of intrinsic subtype, with an efficacy analysis based on classification of tumors using the genomic grade index (GGI) as an exploratory objective. This trial design is intended to establish proof of concept that RIDA-DALO can prolong PFS in ER+ breast cancer in all-comers or a high proliferation subset by Ki67, while efficiently addressing the development of two investigational agents in combination and leading to a two-arm Phase 3 design.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr OT3-01-16.
P1-01-08: Expression of Interleukin-15 (IL-15) and the IL-15 Receptor in Human Breast Cancer.
Authors: Sanders AJ , Ye L , Wei XQ , Mansel RE , Jiang WG 
Published: June 2012

Abstract
Introduction: Interleukin-15 (IL15) is a cytokine that influences activation and proliferation of T-lymphocytes. IL-15 is produced in the body leukocytes such as phagocytes and in many ways has similar immunoregulatory functions to IL-2 including stimulation of NK cells and CD8(+) T cells. It has been suggested that IL-15 may increase the immunity to cancer cells and cancer cell's response to therapeutic agents. IL-15 has also been shown to be able to inhibit tumour growth in vivo. However, the expression profile of IL-15 and IL-15 receptor (IL-15) in solid tumours including human breast cancer is not clear. The present study investigated the expression profile of both IL-15 and IL-15R in human breast cancer and deduced a clinical and pathological relevance with breast cancer.
Methods: Immunohistochemical methods were used to detect IL-15 and IL-15RA in mammary tissues. IL-15 and IL-15RA transcripts were analysed using real-time quantitative PCR method. Levels of IL-15 and IL-15RA were compared in normal and tumour tissues as well as against tumour staging, nodal status, disease progression and clinical outcome after a 10-year followup.
Results: Both IL-15 and IL-15RA were detectable in mammary tissues and were seen in both epithelial cells and infiltrating cells. Node positive tumours had low levels of IL-15 compared with node negative tumours (21.7±10 vs 103±46, respectively). Late stage tumour also had lower levels of IL-15 (95±43, 31±15, 3.7±2 and 1.3±1.15 for stage I, II, III and IV tumours respectively. p=0.036 and p=0.032, stage-II and Stage-III vs stage-I). Patients with metastatic disease (10.3±3) and patients died of breast cancer related conditions (8.5±6) had markedly low levels of IL-15 when compared with those who were disease free (54.7±25). The disease free survival time for patients with low levels IL-15 was 126 (114-138, 95%CI) months, compared with 139 (131-148) months for those with high levels of IL-15. Despite the reduced expression of IL-15 in aggressive tumours, expression of IL-15 receptor, IL-15RA, did not display a significant change and failed to showed a link with nodal status, tumour staging and clinical outcome.
Conclusions: Interleukin-15, an immuoregulatory cytokine, has an aberrant expression in human breast cancer. Low levels of IL-15, but not IL-15 receptor, is associated with the aggressiveness and disease progression of breast cancer. Together with reported effect of IL-15 on NK cells and other anti-tumour lymphocytes, IL-15 appears to be a useful therapeutic option.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-01-08.
P1-01-13: Prognostic Impact of CD8 in Node-Negative Breast Cancer.
Authors: Schmidt M , Chen Z , Hellwig B , Böhm D , Lebrecht A , Gebhard S , Gehrmann M , Koelbl H , Hengstler JG 
Published: June 2012

Abstract
Background: Infiltration of cytotoxic T lymphocytes (CTL) is a common feature in breast cancer. We examined the prognostic impact of CD8 positive CTL in formalin-fixed-paraffin-embedded (FFPE) tissue using immunohistochemistry (IHC) in node-negative breast cancer and validated our findings in previously published cohorts using RNA expression.
Methods: CD8 was evaluated in FFPE tissue of 339 medically untreated node-negative breast cancer patients utilizing IHC. Results were validated utilizing microarray based gene-expression data of four cohorts of medically untreated node-negative breast cancer patients (n=824). Impact of CD8 on metastasis-free survival (MFS) was analyzed with univariate and multivariate Cox regression. Meta-analysis of previously published cohorts was performed using a random effects model. Prognostic significance was examined in the whole cohort and in different molecular subtypes (ER+/HER2−, ER−/HER2−, HER2). Correlation between RNA expression and IHC was analyzed according to Spearman.
Results: Immunohistochemical detection of CD8+ CTL was associated with MFS in univariate (hazard ratio [HR] 0.76, 95% confidence interval [95% CI] 0.59−0.98, P=0.037) as well as in multivatiate analysis (HR 0.61, 95% CI 0.46−0.81, P=0.001). Protein levels of CD8 had a good correlation with RNA expression (r=0.488). Higher RNA expression of CD8 was related to better MFS in a meta-analysis of the whole cohort (HR 0.74, 95% CI 0.60−0.90, P=0.0023). However, prognostic significance was confined to ER+/HER2− (HR 0.71, 95% CI 0.51−0.99, P=0.0201) and HER2+ (HR 0.60, 95% CI 0.38−0.97, P=0.037) but not to ER−/HER2− molecular subtypes (HR 0.77, 95% CI 0.52−1.14, P=0.1965).
Conclusion: CD8 positive CTL have independent prognostic significance in node-negative breast cancer.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-01-13.
P1-02-04: Estrogen Receptor beta Inhibits Breast Cancer EMT by Regulating the Expression of miR-200.
Authors: Thomas C , Gayani R , Nikolos F , Hao R , Katchy A , McCollum C , Williams C , Bondesson M , Krishnamurthy S , Esteva F , Gustafsson J-A 
Published: June 2012

Abstract
Estrogen receptor beta (ERβ) mediates the effects of estrogens in a variety of human tissues and regulates cellular processes involved in initiation and progression of breast cancer such as cell proliferation and migration. Clinical studies produced contradictory data regarding the role for ERβ in prognosis of metastatic breast cancer and the molecular mechanism through which ERβ influences cell migration and invasion has not been fully elucidated. Here we show that induction of ERβ expression inhibits epithelial to mesenchymal transition (EMT) in metastatic breast cancer cells. This correlates with an ERβ-mediated induction in the expression of the epithelial marker E-cadherin and downregulation of its transcriptional repressors ZEB1 and SIP1. ERβ alters the expression of ZEB1 and SIP1 by inducing the expression of the miR-200a, miR200b and miR-429. Downregulation of these miRNAs in ERβ-expressing cells resulted in decreased cell-cell contact and decline of E-cadherin levels. In addition, ERβ was found to inhibit the invasiveness of metastatic breast cancer cells in a zebrafish xenotransplantation model. We are now examining breast cancer specimens derived from ductal carcinomas and metaplastic breast cancers to see whether ERβ levels decline in the mesenchymal regions and ERβ expression is correlated with epithelial markers. These data propose a crucial role for ERβ in the regulation of EMT and in prognosis of invasive and metastatic breast cancer.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-02-04.
P1-02-11: The BCL2 Antagonist of Death, BAD Is Down-Regulated in Breast Cancer and Inhibits Cancer Cell Invasion.
Authors: Cekanova M , Fernando R , Wimalasena J 
Published: June 2012

Abstract
Background: Recent clinical evidence suggest that expression of BCL2 and its antagonist BAD are good prognosticators for survival in breast cancer patients. BAD protein was previously shown by us to inhibit cyclin D1 expression and cJun activation, both may enhance invasiveness of tumor cells(Fernando et al JBC 07). However, the role of BAD and other BCL2 family proteins in invasion/metastasis of breast cancer is poorly characterized.
Methods: By immunohistochemistry nuclear and cytoplasmic staining of several proteins including BAD in normal epithelial was compared to that of cancer cells in human specimens. Western blotting and ELISA methods were used to compare BAD overexpressing MCF7 breast cancer cells with control cells for the expression of variety of signaling molecules, proteins that take part in metastasis and invasion and ability of cells to invade was measured. PCR was used to measure m RNA levels and reporter constructs utilized for transcriptional factor activity studies.
Results: Grade II breast cancer specimens express less total and phosphorylated forms of BAD in nuclei and cytoplasm compared to normals. BAD expression decreased Sp1, β-catenin and STAT proteins, which may increase cyclin D1 in vitro. BAD inhibited activation of the CRE and AP1 elements, and phosphorylation of BAD on S112 and S136 is required for this activity. BAD inhibited the Ras/MEK/ERK pathway and JNK, which may underlie inactivation of c Jun. BAD, like BCL2, may decrease metastasis,therefore, ability of BAD to modulate the expression of metastasis related proteins were measured and MMP10, VEGF, SNAIL, CXCR4, E-cadherin, and ***TlMP2 were regulated by BAD with a concomitant reduction in cell invasion.
Conclusion: Higher expression of BAD in breast cancer and a role in metastasis and proliferation suggests that BAD is valuable prognostic marker in breast cancer and a multi functional protein. Further given the overwhelming clinical evidence that BCL2 prolongs survival, a reevaluation of the role of BCL2 family proteins in metastasis is urgently required.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-02-11.