bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P5-03-03: Designing a novel platinum chemotherapeutic (IO-125) for treatment of breast cancer
Authors: Sengupta A , Roy M , Sarkar A , Mylavarapu S , Modi S , Gupta N , B H , Hossain S , Ansari A , Pandey M , Yadav Y , Sengupta S 
Published: May 2016

Abstract
Triple-negative breast cancer (TNBC) is an aggressive form of cancer occurring in 15-20% of breast cancer patients, with most patients relapsing on currently approved therapy. Recent studies have shown activity of platinum chemotherapy in this class of patients. IO-125 is a novel platinum (II) chemotherapeutic agent with an unique coordination environment. In this study, we investigated the anti-tumor activity of IO-125 in pre-clinical models of TNBC.
The coordination environment in IO-125 facilitates supramolecular assembly and releases diaminocyclohexane (DACH)-platinum in a sustained pH-dependent manner. In vitro cell viability studies using an array of breast cancer cell lines shows IO-125 exerts increased potency compared to carboplatin or oxaliplatin. The maximum tolerated (platinum-equivalent) dose (MTD) of IO-125 in mice was 8-fold higher than the MTD (platinum-equivalent) dose of oxaliplatin. The biodistribution and pharmacokinetic profile of IO-125 in plasma and tumor revealed preferential tumor accumulation, significantly increased area-under-the-curve (AUC), a reduction in clearance (CL) and a longer terminal half-life (42 hours) in comparison to oxaliplatin (18 hours). In addition, DNA-Pt adduct formation in tumors was significantly higher for IO-125. When administered at their respective MTDs, IO-125 led to sustained regression of the tumor in a 4T1 syngeneic breast cancer model. Based on these observations, we conclude that IO-125 may emerge as a novel therapeutic against triple negative breast cancer.
Citation Format: Sengupta A, Roy M, Sarkar A, Mylavarapu S, Modi S, Gupta N, B H, Hossain S, Ansari A, Pandey M, Yadav Y, Sengupta S. Designing a novel platinum chemotherapeutic (IO-125) for treatment of breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-03-03.
Abstract P5-05-02: Regulation of glucose metabolism by the RUNX2 transcription factor has a negative impact on mitochondrial function in breast cancer cells
Authors: Kim MS , Choe M , Cho H , Polster BM , Girnun GD , Passaniti A 
Published: May 2016

Abstract
The RUNX2 transcription factor regulates breast cancer (BC) metastasis to bone and is itself a target of IGF-1 signaling pathways. We have shown that glucose can activate RUNX2 phopshorylation through IGF-1 receptor signaling and that RUNX2 was associated with inhibition of pyruvate dehydrogenase (PDHA1) activity and repression of mitochondrial respiration in BC cells. However, the mechanisms by which RUNX2 alters mitochondrial function and supports an oncogenic phenotype are not completely known. RUNX2 expression in a luminal BC cell line increased expression of glycolytic genes, and sensitivity to glucose starvation. However, RUNX2 knockdown in a triple-negative BC cell line inhibited expression of glycolytic genes. RUNX2 also repressed mitochondrial oxygen consumption rates (OCR), a measure of oxidative phosphorylation while overexpression of SIRT6, a NAD-dependent histone deacetylase, increased respiration in RUNX2-positive cells. RUNX2 repressed SIRT6 expression directly at the transcriptional and post-translational levels. High SIRT6 expression was observed in normal mammary tissue and cells that did not express RUNX2 but endogenous SIRT6 expression was low in malignant BC tissues or cell lines, which expressed high levels of RUNX2. These results suggest that SIRT6, a known tumor suppressor, was a critical mediator of these RUNX2-regulated metabolic changes. These results support a hypothesis whereby RUNX2 upregulation during BC progression leads to inactivation of the SIRT6 tumor suppressor to promote tumorigenesis. It will be important to investigate further changes in mitochondrial function to understand the precise mechanisms by which RUNX2 regulates BC metabolism.
Citation Format: Kim MS, Choe M, Cho H, Polster BM, Girnun GD, Passaniti A. Regulation of glucose metabolism by the RUNX2 transcription factor has a negative impact on mitochondrial function in breast cancer cells. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-05-02.
Abstract P5-06-03: Effect of obesity on molecular characteristics of invasive breast tumors: Gene expression analysis of 405 tumors by BMI
Authors: Ellsworth RE , Toro AL , Costantino NS , Shriver CD , Ellsworth DL 
Published: May 2016

Abstract
Background: Obesity is a risk factor for breast cancer in postmenopausal women and weight gain after diagnosis is associated with decreased survival and less favorable clinical characteristics such as greater tumor burden, higher grade, and poor prognosis, regardless of menopausal status. Despite the negative impact of obesity on clinical outcome, the molecular mechanisms by which excess adiposity influences breast cancer are not well-understood.
Methods: Affymetrix U133 2.0 gene expression data was available for 405 primary breast tumors and 20 tumor-adjacent adipose tissues; RNA was isolated from tumor epithelia or adipose using laser microdissection. Patients were classified as lean (BMI&lt;25), overweight (BMI 25-29.9) or obese (BMI&gt;30). Statistical analysis was performed by ANOVA using Partek Genomics Suite version 6.6.
Results: Obese patients were significantly more likely to be diagnosed &gt;50 years and to be of African American ancestry compared to lean or overweight women, while pathological characteristics including tumor stage, size or grade, lymph node status and intrinsic subtype did not differ significantly between groups. Principal component analysis could not effectively cluster the tumors by weight and no genes were differentially expressed using a false discovery rate &lt;0.05. Using a less stringent unadjusted P-value of &lt;0.01, 329 genes were differentially expressed, however, this gene expression profile could not discriminate patient tumors by BMI. In contrast, BMI was effective in clustering tumor-adjacent adipose samples by BMI based on differential expression of 156 genes.
Conclusions: Although tumor epithelial cells from obese women do not differ significantly from those of lean and/or overweight women at the gene expression level, tumor-adjacent adipose did differ by weight. These data demonstrate that less favorable outcomes in obese patients are not be attributable to the tumor itself but to influences from the microenvironment and suggest that decreasing breast adiposity may be an effective strategy to reducing risk and improving outcomes in obese women.
Citation Format: Ellsworth RE, Toro AL, Costantino NS, Shriver CD, Ellsworth DL. Effect of obesity on molecular characteristics of invasive breast tumors: Gene expression analysis of 405 tumors by BMI. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-06-03.
Abstract P5-08-19: A single-nucleotide polymorphism in the 3'-UTR region of the adipocyte fatty acid binding protein 4 gene is associated with prognosis of triple negative breast cancer
Authors: Yuan P , Wang W , Wu C , Lin D , Xu B 
Published: May 2016

Abstract
Objective Triple negative breast cancer (TNBC) is a subtype with poor prognosis and high heterogeneity. The aim of this study was to screen single nucleotide polymorphisms (SNPs) associated with the prognosis of TNBC patients and to explore the potential mechanism.
Methods We selected SNPs(MAF≥1%) located on the 3' untranslated region (3'UTR) of differentially expressed genes in breast cancer through databases (Nextbio,ensemble,NCBI,MirSNP). We investigated the possible associations between 111 SNPs and progression risk among 323 TNBC patients using two-step case-control study with discovery cohort (n=162) and validation cohort (n=161). The Benjamini Hochberg false discovery rate (FDR) method was used to assess the statistical significance after correction for multiple comparisons. Kaplan-Meier analysis was applied in order to assess the association between disease free survival (DFS) and positive SNPs, as well as Body Mass Index(BMI). We also investigated the expression of FABP4 in adipocytes adjacent to TNBC tissues (n=35) using immunohistochemistry. The integrated optical density (IOD) was measured as an approximation of FABP4 expression. Mann-Whitney U test was used in an attempt to assess the correlations among SNPs in FABP4, FABP4 expression and TNBC prognosis.
Results SNPs in FABP4, KRAS and NTRK2 genes associated with the recurrence risk of TNBC throughout the discovery cohort and validation cohort, while the statistical significance was retained after multiple comparisons only for FABP4 rs1054135. The G allele of rs1057035 was associated with decreased risk of disease progression (aHR 0.14, 95%CI0.03-0.66), as well as an increased DFS (P&lt;0.05). Furthermore, the expression of FABP4 was statistically significant lower in patients with rs1054135-GG genotype and those in disease-free group(P=0.0464,P=0.0061 respectively).
Conclusions Our study found a lipid metabolism related gene and an important SNP in the 3'UTR of FABP4 associated with TNBC prognosis, which may aid the screening of high-risk patients with TNBC recurrence and the development of novel chemotherapeutic agents.
Citation Format: Yuan P, Wang W, Wu C, Lin D, Xu B. A single-nucleotide polymorphism in the 3'-UTR region of the adipocyte fatty acid binding protein 4 gene is associated with prognosis of triple negative breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-08-19.
Abstract P5-09-07: Using the power of the internet to deliver breast teaching in Africa
Authors: Shaaban AM , Abdulkareem F , Rotimi O 
Published: May 2016

Abstract
Introduction:
Delivering high quality breast teaching to African countries is of utmost importance. Our previous audit of breast cancer reporting in Africa has identified areas that would benefit from teaching and education. However, time and resource issues limit the ability to deliver teachings to a large number of African pathologists in person.
Method
As part of a comprehensive national in house teaching for senior trainees in Nigeria, a distant module of teaching was delivered by a team of UK pathologists using a freely available internet application.
Results
Distant teaching formed part of a two week residential postgraduate histopathology course that was designed for trainees preparing for their exit Histopathology exam. Sixty African pathologists attended the teaching. Previous auditing of breast cancer reporting indicated the need for education on macroscopic specimen handling, typing and grading of breast cancer. Other topics included an update on inflammatory breast cancer which has a high incidence in Africa and columnar cell lesions that are increasingly being encountered by African pathologists in the context of breast screening. A set of anonymous virtual slides were scanned and distributed to delegates before the course date.
Teaching was delivered using Skype application that only required a computer with internet access at the UK and Nigeria. We utilised video-conferencing which allowed trainees to see their lecturers and vice versa. The new data sharing facility of the application allows simultaneous sharing of Power Point presentations, with annotation which facilitates interactive discussion. A slide seminar using the previously circulated virtual slides, covering areas of diagnostic challenges morphologically and by immunohistochemistry was also delivered. An approach to diagnosing these lesions was delivered with re-focussing on tumor typing and grading. Participants were able to ask questions and interact with the UK-based tutors thorough the sessions. The feedback collected from attendees was excellent.
Conclusion
Distant teaching using freely available internet applications is a valuable, time and cost effective method that allows sharing educational material including lectures and slide seminars in an interactive manner. It is particularly useful in delivering teaching to resource-poor countries.
Citation Format: Shaaban AM, Abdulkareem F, Rotimi O. Using the power of the internet to deliver breast teaching in Africa. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-09-07.
Abstract P5-14-03: A network meta-analysis of fulvestrant 500 mg versus alternative therapies for second-line treatment of postmenopausal, estrogen receptor-positive advanced breast cancer
Authors: Telford C , Jones N , Batson S 
Published: May 2016

Abstract
Background
A network meta-analysis (NMA) of randomized controlled trials compared overall survival (OS) and serious adverse events (SAEs) of fulvestrant 500 mg with alternative therapies for second-line treatment of postmenopausal, estrogen receptor-positive advanced breast cancer.
Methods
Data were identified by systematic literature review. Study level hazard ratios (HRs) were obtained by modeling survival data using Weibull distribution, based on statistical and visual fit. SAEs were calculated as rate of grade 3/4 adverse events per patient year. Fixed effect Bayesian NMA were conducted for both outcomes.The base case included the following comparators of interest: anastrozole 1 mg, letrozole 2.5 mg, fulvestrant 250 mg, exemestane 25 mg, everolimus 10 mg plus exemestane 25 mg. The first three comparators were included in a subgroup analysis of treatment post-antiestrogen (antiestrogen subgroup), the last three were included in a subgroup analysis of treatment post-aromatase inhibitor (aromatase inhibitor subgroup).
Results
Ten studies were included; all studies reported SAEs, 7 studies reported OS. In the base case, fulvestrant 500 mg improved OS versus all comparators and in the antiestrogen subgroup versus fulvestrant 250 mg (HR 0.74; 95% credible interval [CrI] 0.56, 1.00), anastrozole (HR 0.73; 95% CrI 0.52, 1.03), and letrozole (HR 0.69; 95% CrI 0.44, 1.09). In the aromatase inhibitor subgroup, fulvestrant 500 mg improved OS versus fulvestrant 250 mg (HR 0.89; 95% CrI 0.59, 1.33) and exemestane (HR 0.93; 95% CrI 0.58, 1.47); OS for fulvestrant 500 mg versus everolimus plus exemestane was similar (HR 1.02; 95% CrI 0.62, 1.69). Decreased SAE rates were seen for fulvestrant 500 mg versus letrozole, exemestane, and everolimus plus exemestane (13.22 versus 20.65, 46.63, 67.30 events, respectively) in base case and versus fulvestrant 250 mg and letrozole (14.88 versus 15.67, 23.41 events, respectively) in the antiestrogen subgroup. NMA in the aromatase inhibitor subgroup was not performed (lack of reporting SAEs).
Conclusions
This analysis suggests improved efficacy for fulvestrant 500 mg versus fulvestrant 250 mg and aromatase inhibitors, similar efficacy to everolimus plus exemestane, and decreased toxicity amongst a majority of the comparators. Fulvestrant 500 mg can be considered an efficacious and better tolerated alternative endocrine treatment in this setting.
Citation Format: Telford C, Jones N, Batson S. A network meta-analysis of fulvestrant 500 mg versus alternative therapies for second-line treatment of postmenopausal, estrogen receptor-positive advanced breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-14-03.
Abstract P6-02-01: Screening mammography in women over age 75: Is it beneficial?
Authors: Cate SP , Kohli MK , Gillego A , Chadha M , Fulop T , Boolbol SK 
Published: May 2016

Abstract
Background:
In 2015 the U.S. Preventive Services Task Force (USPSTF) stated that there was insufficient evidence for the use of screening mammography in women aged 75 and older. This statement was based on the lack of randomized controlled trials demonstrating survival benefit in this population. As per the American College of Radiology, the acceptable cancer detection rate via screening mammography is at least 2.5 cases per 1000 examinations for an institution, with reported rates as high as 4.7 cases per 1000.
Aim:
In this study, we sought to examine our institution's practice of screening mammography for women 75 years and older. We aimed to determine the incidence of cancer detection in this age group through screening mammography.
Methods:
A search was performed to identify women aged 75 and above who underwent screening mammography at Mount Sinai Beth Israel Medical Center between January 1, 2013 and December 31, 2014. Patients classified as BIRADS 0 on initial screening were reclassified based on their subsequent diagnostic imaging, if performed. A chart review was performed for those patients who underwent breast biopsies to obtain their pathology results.
Results:
In this two year period, 2057 patients aged 75 and older underwent screening mammography. The majority of women in this age group had non-actionable results of their screening mammography, and were classified as BIRADS 1 or 2 (96%). There were a total of 49 patients who had BIRADS 3 final results (2.4%). Twenty-two patients had screening mammograms that were classified as BIRADS 4 (1.1%). Biopsies revealed 6 invasive ductal carcinomas, 4 cases of in situ carcinoma, 2 cases of duct ectasia, 2 intraductal papillomas, 3 fibrocystic biopsies, and 3 fibroadenomas. In total, 10 of 2057 patients were diagnosed with breast cancer (0.5%).
Mammography results from 2013-2014Final radiologic classificationNumber of patientsPercent of populationBIRADS 182940.3%BIRADS 2114755.7%BIRADS 3492.4%BIRADS 4221.1%BIRADS 500%BIRADS 0100.5%Total screening mammograms2057
Conclusions:
In our institution, 98.4% of women aged 75 and older had screening mammography with benign results. Ten women in this group were found to have breast cancer. The breast cancer detection rate in this cohort was 4.9 per 1000 screening examinations, which is nearly double the cited recommendation put forth by the American College of Radiology. These results are certainly relevant when considering appropriateness of annual screening mammography in this age group.
Citation Format: Cate SP, Kohli MK, Gillego A, Chadha M, Fulop T, Boolbol SK. Screening mammography in women over age 75: Is it beneficial?. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-02-01.
Abstract P6-11-06: Time and value of chemotherapy administration burden in a Swedish hospital
Authors: Nilsson A , Lundkvist J , Lindman H 
Published: May 2016

Abstract
Background
Administration of treatment for cancer patients can require substantial health care resources and differences in administration burden between treatments are therefore important to take into account when comparing them. Besides the direct personnel and bed time, the administration can also have broader consequences on the organisation and process of care delivery, as well as on the patients. How to value differences in these parameters is however not straightforward.
Nab-paclitaxel and paclitaxel are examples of two treatments with important differences in administration burden, and the objective of this study was to perform a time-motion study to compare time required for treatment administration.
Material and methods
Breast cancer patients vising the oncology day care unit at the department of oncology at Akademiska Hospital in Uppsala, Sweden, as part of their regular treatment-course with nab-paclitaxel (n=13) or paclitaxel (n=9) were included in the study.
Time data collection was based on a questionnaire answered by hospital staff. Time for infusions and the total patient time in hospital were measured for each patient.
Results
Mean infusion times per administration of nab-paclitaxel and paclitaxel were 42.1 (Standard deviation (SD) 20.7) minutes and 104.3 (SD 43.3) minutes, respectively. Total patient times in clinic per infusion were 82.2 (SD 40.9) minutes and 183.9 (SD 34.8) minutes, respectively.
A 12-week treatment course of nab-paclitaxel (every three weeks), nab-paclitaxel (weekly) and paclitaxel (weekly) would require in total 2.8, 8.4 and 20.9 hours of infusion time, respectively. The corresponding patient time in hospital would be 5.5, 16.4 and 36.8 hours, respectively.
Conclusion
There can be substantial differences in nurse and facility resources required for administration of chemotherapy, our data showed approximately a 7-fold difference in patient, personnel and facility time requirements between the compared treatments.
In a time with shortage of both hospital personnel and facilities, the valuation of these resources is not easy and may have broader impact on the organisation and delivery of care. Monetary valuation using rent cost or salaries may in a time of resource shortage underestimate the true opportunity cost, and more research and discussions on how to prioritise use of these resources versus other costs are therefore needed.
Citation Format: Nilsson A, Lundkvist J, Lindman H. Time and value of chemotherapy administration burden in a Swedish hospital. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-11-06.