bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of ITO‐Silver Wire Electrode Structure on the Performance of Single‐Crystal Silicon Solar Cells
Authors: Jheng Wern-Dare
Published: June 2012

This study aimed to explore the effect of various electrode forms on single‐crystal silicon solar cells by changing their front and back electrode structures. The high light penetration depth of the Indium Tin Oxide (ITO) and the high conductivity of the silver wire that were coated on the single crystal silicon solar cells increased photoelectron export, thus increasing the efficiency of the solar cell. The experiment utilized a sol‐gel solution containing phosphorus that was spin coated on single‐crystal silicon wafers; this phosphorus also served as a phosphorus diffusion source. A p‐n junction was formed after annealing at high temperature, and the substrate was coated with silver wires and ITO films of various structures to produce the electrodes. This study proposed that applying a heat treatment to the aluminum of back electrodes would result in a higher efficiency for single‐crystal silicon solar cells, whereas single‐crystal silicon solar cells containing front electrodes with ITO film coated with silver wires would result in efficiencies that are higher than those achieved using pure ITO thin‐film electrodes.
Generalization of Some Coupled Fixed Point Results on Partial Metric Spaces
Authors: Shatanawi Wasfi , Nashine Hemant Kumar , Tahat Nedal
Published: June 2012

Using the setting of partial metric spaces, we prove some coupled fixed point results. Our results generalize several well-known comparable results of H. Aydi (2011). Also, we introduce an example to support our results.
Seasonal and Local Time Variations ofE-Region Field-Aligned Irregularities Observed with 30.8-MHz Radar at Kototabang, Indonesia
Authors: Otsuka Y.
Published: June 2012

A VHF backscatter radar with operating frequency 30.8 MHz has been operated at Kototabang (0.20°S, 100.32°E; dip latitude 10.36°S), Indonesia, since February 2006. We analyzedE-region field-aligned irregularities (FAIs) observed by this radar through a year of 2007 and found that theE-region FAI observed at Kototabang can be classified into two groups. One is “descending FAI”. Altitude of the FAI echo region descends with time from 102 km to 88 km altitude during 0700–1000 and 1900–0000 LT in June solstice season. The other is “low-altitude FAI”, which is observed in an altitude range from 88 to 94 km mainly during nighttime. The observed Doppler velocity show distinct local time and altitude dependence. The seasonally averaged zonal velocity above (below) approximately 94 km altitude is westward (eastward) during daytime and eastward (westward) during nighttime. Meridional/vertical velocity perpendicular to the geomagnetic fields is upward during daytime and downward during nighttime. The direction of the FAI velocity above approximately 94 km altitude is consistent with that of the backgroundE×Bplasma drifts reported previously.
Flexible LDPC Decoder Architectures
Authors: Awais Muhammad , Condo Carlo
Published: June 2012

Flexible channel decoding is getting significance with the increase in number of wireless standards and modes within a standard. A flexible channel decoder is a solution providing interstandard and intrastandard support without change in hardware. However, the design of efficient implementation of flexible low‐density parity‐check (LDPC) code decoders satisfying area, speed, and power constraints is a challenging task and still requires considerable research effort. This paper provides an overview of state‐of‐the‐art in the design of flexible LDPC decoders. The published solutions are evaluated at two levels of architectural design: the processing element (PE) and the interconnection structure. A qualitative and quantitative analysis
of different design choices is carried out, and comparison is provided in terms of achieved flexibility, throughput, decoding efficiency, and area (power) consumption.
A Review of the Optimisation of Photopolymer Materials for Holographic Data Storage
Authors: Guo Jinxin , Gleeson Michael R. , Sheridan John T.
Published: June 2012

Photopolymers are very interesting as optically sensitive recording media due to the fact that they are inexpensive, self-processing materials with the ability to capture low-loss, high-fidelity volume recordings of 3D illuminating patterns. We have prepared this paper in part in order to enable the recognition of outstanding issues, which limit in particular the data storage capacity in holographic data storage media. In an attempt to further develop the data storage capacity and quality of the information stored, that is, the material sensitivity and resolution, a deeper understanding of such materials in order to improve them has become ever more crucial. In this paper a brief review of the optimisation of photopolymer materials for holographic data storage (HDS) applications is described. The key contributions of each work examined and many of the suggestions made for the improvement of the different photopolymer material discussed are presented.
Alpha-Fetoprotein and Novel Tumor Biomarkers as Predictors of Hepatocellular Carcinoma Recurrence after Surgery: A Brilliant Star Raises Again
Authors: Lai Quirino , Melandro Fabio , Pinheiro Rafael S. , Donfrancesco Andrea , Fadel Bashir A. , Levi Sandri Giovanni B. , Rossi Massimo , Berloco Pasquale B. , Frattaroli Fabrizio M.
Published: June 2012

Alpha-fetoprotein (AFP), des-γ-carboxy prothrombin (DCP), and lens culinaris agglutinin-reactive fraction of AFP (AFP-L3) have been developed with the intent to detect hepatocellular carcinoma (HCC) and for the surveillance of at-risk patients. However, at present, none of these tests can be recommended to survey cirrhotic patients at risk for HCC development because of their suboptimal ability for routine clinical practice in HCC diagnosis. Starting from these considerations, these markers have been therefore routinely and successfully used as predictors of survival and HCC recurrence in patients treated with curative intent. All these markers have been largely used as predictors in patients treated with hepatic resection or locoregional therapies, mainly in Eastern countries. In recent studies, AFP has been proposed as predictor of recurrence after liver transplantation and as selector of patients in the waiting list. Use of AFP modification during the waiting list for LT is still under investigation, potentially representing a very interesting tool for patient selection. The development of a new predictive model combining radiological and biological features based on biological markers is strongly required. New genetic markers are continuously discovered, but they are not already fully available in the clinical practice.
Formation of Au-Silane Bonds
Authors: Yochelis Shira , Katzir Eran , Kalcheim Yoav , Gutkin Vitaly , Millo Oded , Paltiel Yossi
Published: June 2012

Many intriguing aspects of molecular electronics are attributed to organic-inorganic interactions, yet charge transfer through such junctions still requires fundamental study. Recently, there is a growing interest in anchoring groups, which considered dominating the charge transport. With this respect, we choose to investigate self-assembly of disilane molecules sandwiched between gold surface and gold nanoparticles. These assemblies are found to exhibit covalent bonds not only between the anchoring Si groups and the gold surfaces but also in plane crosslinks that increase the monolayer stability. Finally, using scanning tunneling spectroscopy we demonstrate that the disilane molecules provide strong electrical coupling between the Au nanoparticles and a superconductor substrate.
Aberrant Breast in a Rare Site: A Case Report
Authors: Yeniay Levent , Mulailwa Kilongo , Asgerov Elmir , Hoşcoşkun Cüneyt , Zekioğlu Osman
Published: June 2012

Aberrant breast tissue is an anomaly in the embryogenesis of the breast that is found along the mammary ridge or out of that line. We report a case of a 71-year-old female patient with an abdominal aberrant breast tissue found incidentally in a piece of mesenteric biopsy. The histological features were consistent with breast tissue.
A Self-Powered Medical Device for Blood Irradiation Therapy
Authors: Amsel Avigail D. , Rudnitsky Arkady , Zalevsky Zeev
Published: June 2012

Implantable wireless devices may allow localized real-time biomedical treating and monitoring. However, such devices require a power source, which ideally, should be self-powered and not battery dependent. In this paper, we present a novel self-powered light therapeutic device which is designed to implement blood irradiation therapy. This device is self-powered by a miniaturized turbine-based generator which uses hydraulic flow energy as its power source. The research presented in this paper may become the first step towards a new type of biomedical self-operational micromechanical devices deployed for biomedical applications.
Trigonometric Approximation of Signals (Functions) Belonging toW(Lr, ξ(t))Class by Matrix(C1·Np)Operator
Authors: Singh Uaday , Mittal M. L. , Sonker Smita
Published: June 2012

Various investigators such as Khan (1974), Chandra (2002), and Liendler (2005) have determined the degree of approximation of 2π-periodic signals (functions) belonging to Lip(α,r)class of functions through trigonometric Fourier approximation using different summability matrices with monotone rows. Recently, Mittal et al. (2007 and 2011) have obtained the degree of approximation of signals belonging to Lip(α,r)- class by general summability matrix, which generalize some of the results of Chandra (2002) and results of Leindler (2005), respectively. In this paper, we determine the degree of approximation of functions belonging to Lip αandW(Lr,ξ(t)) classes by using Cesáro-Nörlund(C1·Np)summability without monotonicity condition on{pn}, which in turn generalizes the results of Lal (2009). We also note some errors appearing in the paper of Lal (2009) and rectify them in the light of observations of Rhoades et al. (2011).
BS1-2: Stem and Progenitor Cells and the Origins of Breast Cancer Heterogeneity.
Authors: Smalley MJ , Molyneux G , Melchor L
Published: June 2012

Breast cancer heterogeneity results from different genetic lesions occurring in different stem or progenitor cells of origin. We previously demonstrated that deletion of the Brca1 tumour suppressor in basal stem cells or luminal estrogen receptor negative progenitors in the mouse mammary epithelium resulted in very different tumour phenotypes. Remarkably, the progenitor origin tumours most closely resembled human BRCA1 tumours. Having examined what occurs when the same genetic lesion is made is different cells of origin, we are now examining the results of making different lesions in the same cell. We have knocked out different combinations of Brca2, Pten and p53 in the luminal progenitors and carried out a comparative analysis of the resulting tumours. Confirming the hypothesis that tumour heterogeneity is dependent on both genetic lesion and cell of origin, widely differing tumour phenotypes were generated. Remarkably, one gene combination generated tumours in which the same cells expressed both basal and luminal cell lineage terminal differentiation markers. These results have important implications for our understanding of the origins of tumour cellular heterogeneity.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr BS1-2.
DL1-1: Adaptive Resistance to Targeted Therapies.
Authors: Brugge JS , Muranen T , Zoeller J , Worster D , Iwanicki M , Selfors L , Mills G
Published: June 2012

While therapies that target specific molecular alterations in human tumors are showing significant efficacy in the clinic, drug resistance remains a major obstacle. Studies from our laboratory and others have provided evidence that PI3K- and HER2− targeted therapies induce a program of molecular responses to drug treatment that significantly contributes to drug resistance. Interestingly, we have found that resistance in vitro and in mouse models is significantly enriched in cells attached to basement membrane. This resistance correlates with specific upregulation of the adaptive response in the matrix-attached cells. Importantly, inhibition of key components of the adaptive response, like BCL-2, abrogates the drug-induced adaptive resistance. We propose a model in which matrix-protection from targeted therapies allows survival of a subpopulation of tumor cells associated with matrix/basement membrane which expand and lead to more stable drug resistance.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr DL1-1.
ES2-3: Patient-Derived Xenograft Models for Preclinical Breast Cancer Research: Not Just "Basal" Anymore.
Authors: Lewis MT
Published: June 2012

Translational breast cancer research is hampered by difficulties in obtaining and studying primary human breast tissue, and by the lack of in vivo preclinical models that reflect the range of patient tumor biology accurately. In an effort to overcome these limitations, several groups have recently succeeded in propagating patient-derived breast cancer xenografts representing multiple breast cancer subtypes, including estrogen and progesterone receptor positive, and HER2 positive tumors. In our laboratory, we have developed a diverse set of human breast tumors grown as xenografts in the mammary fat pad of SCID/Beige and NOD/SCID/IL2γ-receptor null (NSG) mice, two relatively new immunocompromised mouse models, under various transplant conditions. In all cases, xenograft lines were established directly from breast cancer patient samples, without intervening culture in vitro, using the epithelium-free mammary fat pad as the transplantation site. Of the conditions tested, xenograft take rate was highest in the presence of a low-dose estradiol pellet without exogenous human fibroblasts. Thirty five stably transplantable xenograft lines representing 27 patients were established, using pre-treatment, mid-treatment, and/or post-treatment samples. Most patients yielding xenografts were “triple-negative” (ER−PR-HER2−) (n=21). However, we were able to establish lines from three ER−PR-HER2+ patients, one ER+PR+HER2−, one ER+PR-HER2−, and one “triple-positive” (ER+PR+HER2+) patients. Serially passaged xenografts show phenotypic consistency with the tumor of origin at the histopathology level, and remarkable stability across multiple transplant generations at both the genomic, transcriptomic, and proteomic levels. Of 27 lines evaluated fully, thirteen xenografts showed metastasis to the mouse lung. These models, in conjunction with others like them, thus serve as renewable, quality-controlled tissue resources, and are proving useful for preclinical evaluation of experimental therapeutics.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr ES2-3.
ES8-1: Breast Reconstruction with Implants and Post-Mastectomy Irradiation: Algorithm and Outcomes.
Authors: Cordeiro PG
Published: June 2012

Breast reconstruction in the face of radiotherapy proposes a unique set of challenges to the plastic surgeon and often alters the algorithm of the reconstruction. The impact of radiation changes on the alloplastic breast reconstruction is unpredictable. The author will review current approaches to reconstruction of the patient if they are to undergo post-mastectomy radiation. The algorithm for reconstruction and outcomes after radiation will be presented.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr ES8-1.
MS2-1: Early Life Exposures and Breast Cancer Risk: Preeclampsia and Puberty.
Authors: Forman MR
Published: June 2012

Women diagnosed with preeclampsia (PE) in pregnancy have a 12–72% reduced risk of breast cancer compared to women with a normotensive pregnancy while her daughter from the index pregnancy also has a lower breast cancer risk than normotensive (NT) daughters. Why is this so? The preeclamptic (PE) pregnancy is highly androgenic with low levels of estrogens and insulin-like growth factor −1 levels. We followed a cohort of offspring of preeclamptic pregnancies and of normotensive pregnancies from birth through 12.8 years to examine whether daughters of the PE pregnancy would delay breast development, have lower estrogens and IGF-1 levels in puberty compared to their normotensive offspring and also compared factors influencing age at onset of puberty in the PE and NT girls. In young pubertal aged girls of 10 years, high dehydroepiandosterone- sulfate levels (DHEAS) but low testosterone levels may reflect the in utero exposures of the PE compared to the NT offspring. By 13 years, PE daughters had a 20% lower risk of breast development (OR= 0.80 95% CI 0.70−1.00). In an examination of the role of early life exposures on age at onset of puberty, we report that age of greatest weight gain in infancy is earlier for the NT (3-6 months) than the PE (6-12 months) and that age of greatest weight gain in infancy is associated with the odds of age at onset of puberty. Our findings and those of others in early life exposures and breast cancer risk provide clues to tailoring the effect of early exposures by maternal morbidity in pregnancy.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr MS2-1.
MS2-3: Breast Cancer and the Environment: Developmental Reprogramming of Cancer Susceptibility by Early Life Environmental Exposures.
Authors: Walker CL
Published: June 2012

In the last two decades it has become appreciated that adverse environmental exposures early in life can have a profound impact on susceptibility to adult diseases such as obesity, cardiovascular disease, diabetes, metabolic syndrome and cancer. The “developmental origins of health and disease” or DOHaD hypothesis, posits that environmental exposures during key periods of tissue development and organogenesis can “reprogram” the cell's epigenome in a way that increases susceptibility to disease later in life. It is now clear that even brief environmental exposures can reprogram developing tissues and profoundly increase risk of developing cancer in adulthood decades after the exposures occurred. This developmental reprogramming has been best appreciated in the context of early life exposures to environmental agents such as xenoestrogens that mimic steroid hormones, with such exposures dramatically increasing susceptibility to hormone-dependent tumors of the breast and reproductive tract later in life. Recent advances in the field of environmental epigenomics have provided data that epigenetic alterations in both DNA methylation and histone methyl marks are induced during developmental reprogramming. In some tissues, xenoestrogens induce these epigenetic alterations via activation of non-genomic signaling, providing a direct link between xenoestrogen exposure and disruption of the cell's epigenetic machinery. For example, xenoestrogeninduced activation of non-genomic PI3K/AKT signaling has been shown to target the histone methyltransferase EZH2, modulating the activity of this epigenetic “writer” and disrupting the proper “installation” of epigenetic histone methyl marks during development. Understanding the nature of the epigenetic reprogramming induced by early life exposures to xenoestrogens (and other environmental agents) has important implications for our understanding of breast cancer susceptibility across the life-course and for identifying effective strategies to prevent this disease.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr MS2-3.
OT1-01-03: A Phase 3 Randomized, Double-Blind, Placebo-Controlled Multicenter Study Comparing Denosumab with Placebo as Adjuvant Treatment for Women with Early-Stage Breast Cancer Who Are at High Risk of Disease Recurrence (D-CARE).
Authors: Goss PE , Barrios CH , Bell R , Finkelstein D , Iwata H , Martin M , Braun A , Ke C , Maniar T , Braun S , Dansey R , Coleman RE
Published: June 2012

Background

Bone is a common site of distant recurrence in women with early-stage breast cancer. Cancer cells are thought to stimulate osteoclast-mediated bone resorption, which releases growth factors and cytokines that promote tumor growth. RANK Ligand (RANKL) is the key mediator of osteoclast-induced bone destruction. In preclinical studies, RANKL inhibition reduced the incidence of bone and lung metastases, suppressed tumor progression, and prolonged survival of tumor-bearing mice. Effects were additive with hormonal, chemotherapy, or targeted therapies. Denosumab is a fully human monoclonal antibody against RANKL, approved in the U.S. for the prevention of skeletal-related events in patients with bone metastases from solid tumors. In patients with castrate-resistant prostate cancer, denosumab significantly improved bone metastasis-free survival (BMFS) compared to placebo. The D-CARE trial evaluates BMFS effects of denosumab in women with stage II or III breast cancer.

Methods: Women with node-positive or locally advanced (T3 or T4) disease, and known hormone and HER-2 receptor status are eligible. Standard-of-care adjuvant or neoadjuvant chemo-, endocrine, or HER-2 targeted therapy, alone or in combination must be planned with curative intent. Women with a prior history of breast cancer (other than ductal carcinoma in situ [DCIS] or lobular carcinoma in situ [LCIS]) or distant metastasis, oral bisphosphonate (BP) use within 1 year or any intravenous BP use are excluded. Patients are randomized 1:1 to receive denosumab 120 mg or placebo subcutaneously monthly for 6 mos, then every 3 mos, for a total of 5 yrs treatment. All patients receive vitamin D (≥ 400 IU) and calcium (≥ 500 mg) supplements. Primary endpoint of this event-driven trial is BMFS. Secondary endpoints include disease-free (DFS) and overall survival. The study is powered for both, BMFS and DFS. Safety, quality of life assessments and biomarkers are additional endpoints. The trial, sponsored by Amgen Inc. and registered with the ClinicalTrials.gov identifier NCT01077154 began enrolling patients in June 2010. PG and DF are supported in part by the Avon Foundation, NY.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr OT1-01-03.
OT1-02-01: Phase II Neoadjuvant Trial of Anthracycline Based Regimens Followed by a Combination with Nanoparticle Almumin-Bound Paclitaxel and Trastuzumab in Patients with Operable T2-3,N0-1,Her2 Positive Breast Cancer.
Authors: Iwamoto M , Takahashi Y , Kimura K , Tanaka S , Uchiyama K
Published: June 2012

Background: Anthracycline and taxane have been widely used and studied in neoadjuvant setting for treatment of locally advanced breast cancer. Various regimens have explored the addition of newer agents to determine safety and efficacy, and pathological complete response(pCR) has been demonstrated to be associated with favorable overall survival in primary breast cancer. In addition, Three year median follow-up data of the TECHNO Trial revealed that the neoadjuvant combination of trastuzumab and chemotherapy resulted in a high chance for a pCR. We conducted a clinical Phase II neoadjuvant trial of Anthracycline based regimens(EC,AC,FEC) followed by a combination with nanoparticle albumin-bound Paclitaxel and Trastuzumab in patients with operable T2-3,N0-1,Her2 positive breast cancer.

Patients and Methods: The study is designed to evaluate EC or AC or FEC followed a combination of nanoparticle almumin-bound Paclitaxel and Trastuzumab as neoadjuvant therapy in patients with Her2 positive locally advanced(T2-3,N0-1) breast cancer. Patients are treated with neoadjuvant EC(Epirubicin 90 mg/m2, Cyclophosphamide 600 mg/m2) or AC(Doxorubicin 90 mg/m2, Cyclophosphamide 600 mg/m2) or FEC(Fluorouracil 500mg/m2, Epirubicin 100 mg/m2, Cyclophosphamide 500 mg/m2) q21d x 4, follosed by a combination with nanoparticle almumin-bound Paclitaxel(260 mg/m2) and Trastuzumab q21d x 4.

Patients undergo surgery 4–6 weeks later from completing chemotherapy. pCR, the primary endpoint is defined as no evidence of invasive tumors in the final surgical sample both in the breast and axillary lymph nodes. Secondary endpoints include objective clinical response rate, disease-free interval, overall survival, rate of breast concerving surgery, and the safety of the treatment.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr OT1-02-01.
OT1-02-02: HALT MBC: HER2 Suppression with the Addition of Lapatinib to Trastuzumab in HER2−Positive Metastatic Breast Cancer (LPT112515).
Authors: Lin N , Danso M , David A , Muscato J , Ellis C , DeSilvio M , Garofalo A , Nagarwala Y , Winer E
Published: June 2012

Background Lapatinib in combination with trastuzumab enhanced anti-tumor activity in HER2−positive breast cancer (BC) preclinical models. In patients (pts) with trastuzumab-treated, HER2−positive metastatic (M) BC, treatment with the combination was associated with longer progression-free (PFS) and overall survival (OS) compared with lapatinib alone. In pts with stage II/III BC, preoperative treatment with the combination plus paclitaxel resulted in significantly higher pathological complete response rates compared with paclitaxel combined with either agent alone. This evidence supports the concept of dual HER2 blockade as a treatment strategy for HER2−positive BC. This present study is designed to evaluate whether the addition of lapatinib improves PFS among women with HER2−positive MBC receiving trastuzumab as maintenance therapy.

Trial Design In this open-label, Phase III study, pts are stratified by line of treatment (first/second) and hormone receptor status (positive/negative) then randomized 1:1 to receive maintenance treatment with either lapatinib (1000mg once daily, continuously) in combination with trastuzumab (6mg/kg once every 3 weeks [Q3W]) or trastuzumab (6mg/kg Q3W) alone. Pts will receive study treatment until disease progression, death, discontinuation due to adverse events or other reasons.

Eligibility Criteria Pts with HER2−positive MBC who have completed 12–24 weeks of first- or second-line treatment with trastuzumab plus chemotherapy and have objective response or stable disease. Pts with stable brain metastasis are eligible if entering the study on second-line treatment.

Specific Aims The primary objective is to compare PFS of lapatinib in combination with trastuzumab to trastuzumab as continued HER2 suppression therapy. Secondary objectives are to evaluate OS, clinical benefit rate, safety and tolerability.

Statistical Methods Efficacy endpoints will be analyzed in the intent to treat population. A total of 193 PFS events from 280 randomized pts will be required to detect a 50% increase in median PFS in pts who receive lapatinib plus trastuzumab compared with trastuzumab (median PFS time is 27 versus 18 weeks, respectively); hazard ratio of 0.67 with an 80% power and a 1-sided type I error of 0.025.

Present and Target Accrual Sixteen of the target 280 pts have been randomized. The trial is currently open for accrual in the United States and Canada.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr OT1-02-02.
OT1-02-03: EGF114299: Safety and Efficacy of an Aromatase Inhibitor (AI) in Combination with Lapatinib (L), Trastuzumab (T) or Both for the Treatment of Hormone Receptor-Positive (HR+), HER2+ Metastatic Breast Cancer (MBC).
Authors: Johnston S , Leigh M , Florance A , Wroblewski S , Gradishar W
Published: June 2012

Background: Data from the L plus letrozole (EGF30008) and the Trastuzumab and Anastrozole Directed Against ER-Positive HER2−Positive Mammary Carcinoma (TaNDEM) studies demonstrated that HER2 targeted and endocrine therapy (ET) is a better strategy than ET alone. In EGF30008, progression-free survival (PFS) in the HER2+ population was statistically significantly longer in the letrozole plus L group compared with the letrozole plus placebo group. The HR was 0.71 (95% CI: 0.53−0.96; stratified log rank P=.019). Median PFS was 35.4 weeks in the letrozole plus L group compared with 13.0 weeks in the letrozole plus placebo group.

The present study (EGF114299) is a phase III, open-label, multicenter trial designed to evaluate benefit in overall survival (OS) provided by L/T/AI and L/AI, in pts with HR+/HER2+ MBC who have received neo-/adjuvant T and ET. It will also provide further data on dual HER2 suppression in an attempt to prevent acquired endocrine resistance.

Trial Design: Pts will be randomized to 1 of 3 treatment arms: L 1000 mg po QD plus T (loading dose of 8 mg/kg followed by maintenance with 6 mg/kg IV q3w plus an AI po QD); T plus an AI; or L 1500 mg po QD plus an AI). Choices of AI include letrozole, anastrozole, or exemestane.

Eligibility Criteria: HR+ (ER and/or PgR) and HER2+ Stage IV MBC pts are to be enrolled. Pts must have received neo-/adjuvant T and ET, and are treatment naive for MBC.

Specific Aims: The primary objective is to evaluate OS of L/T/AI as compared with T/AI. The secondary objectives are to assess: OS in T/AI vs L/AI and T/L/AI vs L/AI; PFS; overall response rate; clinical benefit rate; safety and tolerability; and QoL relative to baseline. A 4-year recruitment is anticipated. More than 200 centers across 25 countries are planned; approximately 50 centers are currently open for enrollment.

Statistical Methods: The study is powered to detect a 42% improvement in the risk of death (HR=0.70) in all pts receiving L/T/AI (median 28.5 months) compared with T/AI (median 20 months). The hypothesis will be tested using a 1-sided test for superiority with a=0.025 with a power of 80%.

Present and Target Accrual: One (1) of 525 pts has been randomized. The majority of eligible pts may reside in countries where T is commercially available and reimbursable, particularly North America and Western Europe. Patients who have participated in previous neo-/adjuvant trials including a T regimen are eligible, provided they meet all other inclusion criteria.

The study is currently recruiting pts, with an anticipated target accrual of 525 patients by March 2016.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr OT1-02-03.
OT2-03-02: Prospective Neo-Adjuvant Registry Trial Linking MammaPrint, Subtyping and Treatment Response: Neoadjuvant Breast Registry – Symphony Trial (NBRST).
Authors: Whitworth P , Beitsch P , Gittleman M , Akbari S
Published: June 2012

Background MammaPrint is performed on a diagnostic multi-gene array featuring >4,500 genes. This platform enables additional gene expression profiles to be analyzed simultaneously on one tumor specimen. BluePrint, an eighty gene Molecular Subtyping Profile, discriminates between three distinctive subtypes; Basal-type, Luminal-type, and ERBB2 (HER2)-type. Studies have shown marked differences in response to neo-adjuvant treatment in groups stratified by MammaPrint and BluePrint.

Trial design A prospective observational, case-only study linking MammaPrint, BluePrint, TargetPrint, TheraPrint (together referred to as the Symphony suite) and possible additional profiles of interest to neoadjuvant treatment response and Distant Metastases Free Survival (DMFS) and Relapse Free Survival (RFS).

20-30 institutions in the US will be invited to contribute clinical patient data from enrolled patients after a MammaPrint, TargetPrint, BluePrint and TheraPrint (Symphony suite) has been successfully performed and the patient has started neo-adjuvant therapy. Treatment is at the discretion of the physician, adhering to NCCN approved regimens or a recognized alternative.

Eligibility criteria

Women with histologically proven breast cancer, who have started or are scheduled to start neo-adjuvant chemotherapy therapy or neo-adjuvant hormone therapy, after successful Symphony suite assessment Age 18–90 Written informed consent No excisional biopsy or axillary dissection No confirmed distant metastatic disease No prior therapy for the treatment of breast cancer

Scope

The scope of this registry study is to measure chemosensitivity as defined by pCR (primary endpoint), or endocrine sensitivity as defined by partial response, (a primary endpoint for neo-adjuvant endocrine therapy and a secondary endpoint for neoadjuvant chemotherapy), metastasis-free survival and relapse-free survival (secondary endpoints) in molecular subgroups, determined by the MammaPrint and BluePrint; as well as correlation to Targetprint and Theraprint read outs in addition to investigating novel response profiles.

Statistical methods

The response rate and corresponding confidence intervals will be presented as a proportion of all patients enrolled. The confidence intervals will be calculated using the normal approximation to the binomial distribution. Comparison of response rates between different molecular subgroups will be conducted using Pearson Chi-square test. Correlation of chemosensitivity and endocrine sensitivity (as defined by pCR) to TheraPrint will be determined using Pearson correlation and linear fit models.

Kaplan-Meier curves for RFS and DMFS will be calculated for different molecular subgroups.

Present accrual and target accrual

The target accrual is to enroll approximately 500 patients in 4 years.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr OT2-03-02.
OT2-04-03: Uptake of a Randomized Breast Cancer Prevention Trial Comparing Letrozole to Placebo in BRCA1/2 Mutations Carriers: The FNCLCC ONCO-03/LIBER Trial.
Authors: Pujol P , Lasset C , Berthet P , Dugast C , Delaloge S , Fricker JP , Chabbert Buffet N , Lemonnier J , Roca L , Mijonnet S , Baudry K , Martin AL
Published: June 2012

Background: Women with germline BRCA1or BRCA2 (BRCA1/2) mutations are an extreme risk population for developing breast cancer, with a life-time risk of 56–80%. Prophylactic mastectomy provides a valid option to reduce such risk, but it considerably affects the quality of life. Medical prevention by aromatase inhibitor that has been recently shown to have preventive effect may thus be an alternative. LIBER is an ongoing, double-blind, randomized phase III trial to evaluate the efficacy of five-years letrozole versus placebo to decrease breast cancer incidence in post-menopausal BRCA1/2 mutation carriers (NCT00673335). We present data on the uptake of this trial. Methods: To evaluate theoretical feasibility, we compared inclusion criteria of women in the LIBER trial (n=113) to characteristics of women entered in the prospective ongoing national GENEPSO cohort (n=1505). Uptake was evaluated through a survey sent to all active centres, with responses obtained from 17 of the 20 (85%) centres. Results: According to characteristics of the women included in GENEPSO cohort (n=1505) and the survey, approximately one third of BRCA1/2 mutation carriers are eligible for this study. From november 2009 to may 2010, 534 women eligible from chart review have been informed by mail of the trial and were invited to an oral information by participating centres. Of them, 44% of women came to the dedicated medical visit. Uptake of drug prevention trial was 32 % of orally informed women and 15 % of overall eligible women. Main reasons of refusal were: potential side effects, probability to receive the placebo and lack of support from the women's physicians. Prior prophylactic oophorectomy and history ***of previous unilateral breast cancer were more frequent in women enrolled in the ONCO-03/LIBER trial than in the French cohort (93% versus 60% and 50 % versus 39 %, respectively), suggesting a higher motivation for medical prevention in these subgroups of patients.

Conclusion: One third of women with a BRCA1/2 mutation are eligible to the ONCO-03/LIBER prevention trial. 32 % of orally informed women and, only 15% of overall eligible women entered the trial. To reach accrual objective (n=308), a greater information of the trial should be offered to women with BRCA1/2 mutation and the trial has been proposed to other countries.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr OT2-04-03.
OT2-07-02: SWOG S0927: A Randomized Double Blind Placebo-Controlled Trial of Omega-3-Fatty Acid for the Control of Aromatase Inhibitor (AI)-Induced Musculoskeletal Pain in Women with Early Stage Breast Cancer.
Authors: Hershman DL , Unger JM , Crew KD , Moinpour CM , Minasian LM , Hansen L , Lew DL , Kaberle K , Wade JL , Meyskens FL
Published: June 2012

Background: Despite the well-proven efficacy of aromatase inhibitors(AIs) for the treatment of hormone-sensitive breast cancer, a significant number of women suffer from musculoskeletal side-effects which can result in early discontinuation of this important medication. Given the proposed anti-inflammatory effects of omega-3-fatty acid and the paucity of therapeutic options for AI-induced arthralgia, it is therefore reasonable to test the efficacy of omega-3-fatty acid in women with breast cancer who have developed moderate to severe joint symptoms after initiating AIs.

Specific aims: To assess if omega-3-fatty acid as compared to placebo causes a reduction in worst joint pain/stiffness in women with AI-associated arthralgias at 12weeks as measured by the modified Brief Pain Inventory (BPI). Additional measures will include the WOMAC, M-SACRAH, FACT-ES and global rating of change, which will be assessed at baseline, 6, 12 and 24 weeks. We will evaluate fasting lipids, hormone levels, serum inflammatory markers (TNF, IL2, CRP), and markers of joint destruction (CTX-II) at baseline, 12 and 24 weeks.

Eligibility criteria:Pts. must have histologically-confirmed stages I-III breast cancer, with no evidence of metastatic disease and undergone definitive breast cancer surgery. Pts must be post-menopausal and currently be taking a third-generation AI —anastrazole(Arimidex®), letrozole (Femara®), or exemestane (Aromasin®) for at least the previous 90 days prior to registration with plans to continue for at least an additional 180 days after registration.The patient must have a worse joint pain/stiffness score of 5 or greater on the 10-point scale of the BPI which started or increased after initiation of AI. Pts must not have taken omega-3-fatty acid supplements within the past 3 months prior to registration.Pts will be randomized to receive 6 capsules daily (at 1,000 mg each; ∼600mg combination of ethyl esters EPA/DHA) of omega-3-fattyacid or matching placebo daily for 24 weeks. Statistical methods:We stipulate an alpha=.05 two-sided test, with an estimated 5% non-adherenceand 20% dropout rate at the primary endpoint evaluation time of 12 weeks after randomization. For a two point difference in worst joint pain/stiffness and a 3.5 point SD at 12 weeks, 222 eligible patients would be required for 90% power under a two-arm normal design. To allow ineligibility rate of 10%, 246 total pts will be enrolled. The study should be activated September 2011. Funding: Supported by National Cancer Institute grant CA037429

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr OT2-07-02.
OT3-01-08: Phase II Study of S-1 Combined with Cisplatin in the First-Line Treatment of Triple Negative Breast Cancer.
Authors: Fan Y , Xu BH
Published: June 2012

Rationale: There is no standard choice of first-line treatment for triple negative breast cancer (TNBC). It is supposed that TNBC may be more sensitive to DNA damage agents such as platinum but resistant to cell cycle specific agents including taxanes and 5-fluorouracil. Currently these hypotheses are under investigation in several ongoing clinical trials. S-1 is an orally administered fluorinated pyrimidine with high activity in non-small-cell lung cancer and gastric cancer. Recently single agent S-1 has been reported to be effective in capecitabine-resistant metastatic breast cancer with a response rate of 27.8% and median TTP of 6.2 months. So it is intriguing to find whether S-1 plus cisplatin would be a valuable regimen in TNBC patients with limited choices of management.

Design: This is a prospective, single-arm phase II study. Eligible patients are treated first with S-1( 80mg/m2, 2 weeks on and 1 week off) and cisplatin (75mg/m2 intravenously day1) every 3 weeks as a cycle for up to 6 cycles, until disease progression, unacceptable toxicity or patient consent withdrawal. If no PD was observed after 6 cycles, patients can remain on S-1 until disease progression, unacceptable toxicity or patient consent withdrawal.

Eligibility: Major inclusion criteria includes: 1. histologically confirmed triple negative breast cancer; 2. advanced patients without prior treatment for locally recurrent or metastatic disease; 3. patients must have received anthracyclines and taxanes in neo/adjuvant setting; 4. at least one measurable disease according to RECIST 1.1; 5. adequate organ function within acceptable range.

Endpoints: The primary endpoint is objective response rate (ORR) and secondary endpoints include progression free survival (PFS), overall survival (OS) and safety profile. Exploratory biomarks will be studied for TS and DPD enzyme expression and genotyping.

Statistical considerations: The expected response rate is around 50% based on the literature, and the null hypothesis is based on a response rate no greater than 30%. According to Simon's two stage phase II design with errors of 0.05 and 0.20 respectively, a minimum of 15 patients would be required in the first stage and totally 46 patients after the second stage. Since a non-compliance rate of 10% is expected, we plan to enroll a total of 50 patients.

Recruitment: Currently it has just been initiated with 1 patient still on screening. The target accrual, as stated above, is 50 patients.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr OT3-01-08.
OT3-01-11: A Randomized, Phase II Multicenter, Double-Blind, Placebo-Controlled Trial Evaluating MetMAb and/or Bevacizumab in Combination with Weekly Paclitaxel in Patients with Metastatic Triple-Negative Breast Cancer.
Authors: Daniel BR , Campone M , Dieras V , Ervin T , Yu W , Paton VE , Xia Q , Peterson A
Published: June 2012

Background

Dysregulation of the HGF/Met pathway has been associated with tumorigenesis in many malignancies, including the basal sub-type of triple-negative breast cancer. MetMAb (RG3638) is a recombinant, humanized, monovalent monoclonal antibody directed against Met. By binding to the extracellular domain of Met, MetMAb selectively blocks ligand binding and subsequent activation by HGF. Pre-clinical data support the efficacy of combining MetMAb with numerous chemotherapy agents and with targeted agents including bevacizumab and erlotinib. In clinic, MetMAb has been generally well tolerated as a single agent (Phase I), in combination with bevacizumab (Phase Ib) and with bevacizumab in a dose escalation/expansion study (Phase Ib)1 as well as in combination with erlotinib in patients with previously treated NSCLC2. The combination of MetMAb + erlotinib in NSCLC demonstrated significant benefit in both PFS and OS in patients with Met diagnostic positive tumors whereas those patients with Met diagnostic negative tumors demonstrated a detrimental effect in both PFS and OS. The most commonly reported adverse events associated with MetMAb are peripheral edema and fatigue.

Methods: This clinical trial is a randomized three-arm Phase II study in patients with triple-negative metastatic breast cancer, which makes up the majority of basal sub-type breast cancer. Patients will be randomized (1:1:1) to either paclitaxel + bevacizumab + placebo; paclitaxel + placebo + MetMAb; or paclitaxel + bevacizumab + MetMAb. The primary endpoint of this study is PFS in all patients and by Met diagnostic status. Secondary endpoints include an evaluation of OS, ORR, safety, and pharmacokinetics. To date, 11 patients have been enrolled, and 10 patients have been treated.

Primary and secondary analyses will include all randomized patients, with patients analyzed according to the treatment arm to which they were assigned. Kaplan-Meier methodology will be used to estimate the median PFS for each treatment arm. An estimate of the HR with 95% CI will be determined using a Cox regression model with an indicator variable for the MetMAb-containing arm. Safety will be assessed through summaries of adverse events and will include all patients who receive any amount of study treatment.

This study remains open for accrual; further details on the trial can be found on the ClinicalTrials.gov website under NCT01186991.

1. Moss et al, In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2–6; Orlando, FL; AACR 2011 (abstr 4717).

2. Spigel et al, J Clin Oncol 29:2011 (suppl; abstr 7505).

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr OT3-01-11.
OT3-02-02: Yoga Compared to Exercise as a Therapeutic Intervention during (Neo)adjuvant Chemotherapy in Women with Stage I-III Breast Cancer.
Authors: Wiedemann F , Büssing A , Halle M , Kiechle M , Kohls N , Ostermann T , Sattler D , Ettl J
Published: June 2012

Background: Psychological and physical distress is high in breast cancer patients receiving neoadjuvant or adjuvant chemotherapy. The ***patients'ability to cope with this distress has an impact on treatment variables, i.e. deliverable chemotherapy dose, tolerabilty of side effects, and finaly treatment completion rate. Exercise intervention studies have shown physiological and psychological benefits when undertaken during cancer treatment. There is also evidence that mind/body interventions such as yoga are useful to manage treatment-related symptoms and anxiety in breast cancer patients. Considering the specific theoretical background of mind/body interventions this ongoing trial aims to elucidate the different effects of yoga and conventional exercise on physical and psychological factors in breast cancer patients undergoing neoadjuvant or adjuvant chemotherapy. Trial design: Longitudinal data collection within an open, prospective, randomized trial using standardized questionnaires about inner correspondence and peacefulness with practices (ICPH), health-related quality of life (EORTC QLC C-30), fatigue (Cancer Fatigue Scale, CFS-D), mindfulness (Freiburg Mindfulness Inventory, FMI), spiritual/religious attitudes and disease coping (SpREUK), and life satisfaction (Brief Multidimensional Life Satisfaction Scale, BMLSS). Patients with newly diagnosed stage I-III breast cancer undergoing neoadjuvant or adjuvant chemotherapy are randomly assigned to receive yoga or conventional exercise on a 1:1 ratio. The yoga intervention consists of a weekly 60-minute Iyengar-Yoga group-session together with individual home-based, selfcontained 20-minute sessions twice a week. The conventional exercise intervention consists of a weekly 60-minute physiotherapy exercise session together with individual home-based, selfcontained 20-minute sessions twice a week. Data assessments via questionnaires are done at baseline, right after the 12-week intervention period and 2 months after the end of intervention. Statistical analysis includes analysis of variance with all collected parameters and analysis of correlation between ICPH and above parameters. For statistical power 1-β=0.8 and twosided probability of error a=0.05 the target accrual is 120 patients. Patient accrual within two breast care units started in April 2011 with 12 patients being on study to date (2011, June 21). Planned period of accrual is 20 months.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr OT3-02-02.