bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P1-09-26: Surgery for breast cancer in the elderly is associated with better outcomes
Authors: Jauhari Yasmin A , Chaichanavichkij Pam , Sainsbury Richard J 
Published: May 2015

Abstract
Background
Breast cancer often presents differently in the elderly with more neglected disease. There is patchy evidence to support surgery as a preferred management tool with a positive survival outcome. The objective of this study was to 1. Understand disease presentation and management of patients diagnosed with breast cancer over the age of 80, and 2. To review survival outcome between conservative and surgically managed elderly breast cancer patients.
Method
A retrospective single centre case series was conducted from 2008 to 2014 on patients aged 80 and over at breast cancer diagnosis. Survival outcome between conservative and surgical treatment groups were reported by Kaplan Meier analysis, with comparison by log-rank test.
Results
There were 156 patients, with a median age of 86.6 years (range 80 – 107). 67.9% had invasive ductal carcinoma.
At presentation, 9.6% had T4 fungating lesions and 11.9% had distant metastatic disease. The median tumour size was 25mm (range 4 – 85mm) and 81.5% were oestrogen receptor positive.
Conservative treatment (44.9%, n = 70) was accounted for in 80% of cases by patient choice and/or pre-morbid status precluding surgery. 55.1% of patients underwent surgical resections, the majority of which were performed with curative intent (96.4%). 11 patients had surgery under local anaesthetic with no complications. Median duration of hospital stay was 1 day.
Conservative vs. surgical cohorts were comparable in co-morbidities aside from age (89.6 +/- 5.1 vs. 85.2 +/- 4.2 years, p = 0.005)) and dementia (18 vs. 9 (p = 0.015). The overall survival for those treated conservatively was 29 +/- 4.1 months compared to 40 +/- 6.1 months (p = 0.004) for those having surgery.
Conclusion
The elderly are more likely to present with advanced or neglected breast cancer. Those undergoing surgery had a significant survival advantage and this modality should be offered unless co-morbidities are severe.
Citation Format: Yasmin A Jauhari, Pam Chaichanavichkij, Richard J Sainsbury. Surgery for breast cancer in the elderly is associated with better outcomes [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-09-26.
Abstract P1-10-03: NSABP B-43 is unlikely to produce a cost-effective treatment strategy for HER2+ DCIS
Authors: Alvarado Michael D , Hayes Mitchell T , Sethi Rajni , Ozanne Elissa 
Published: May 2015

Abstract
Background. National Surgical Adjuvant Breast and Bowel Project (NSABP) B-43 is an ongoing randomized clinical trial that compares breast conserving surgery, radiation therapy, and two infusions of trastuzumab to breast-conserving surgery and radiation only for HER2+ ductal carcinoma in situ (DCIS). We sought to identify, from a societal perspective, the level of risk reduction observed in this trial that would be required to make treating HER2+ DCIS patients with trastuzumab cost-effective.
Methods. We developed a Markov decision-analytic model to evaluate these treatment strategies in terms of life expectancy, quality-adjusted life years (QALYs), costs, and the incremental cost-effectiveness ratio (ICER) over 15 years. The results of NSABP B-43 are pending. We therefore assumed the hazard reduction to be 36%, based on the statistical considerations of the trial protocol and explored this in sensitivity analyses. A series of one and two-way sensitivity tests were conducted.
Results. The baseline ICER for switching from a breast-conserving surgery and radiation strategy without trastuzumab treatment to a breast-conserving surgery and radiation strategy with trastuzumab treatment is $1.57 million per life-year gained and $299,616.73 per QALY gained. Compared to a societal willingness-to-pay threshold of $100,000 per QALY gained, adding Herceptin treatment is not cost-effective in the treatment of DCIS under these baseline conditions. In a one-way sensitivity test, we found that the Herceptin strategy only became cost-effective at an 88.3% risk reduction for local recurrence. The model was not sensitive to any costs or probabilities within 20% of baseline values. The model was sensitive to the utilities of having had breast-conserving surgery and radiation with and without trastuzumab treatment. It was not sensitive to other utilities within 0.05 of baseline values.
Conclusions. High risk DCIS treated with breast-conserving surgery and radiation has a low risk of local recurrence as demonstrated in multiple randomized trials. The addition of a costly drug in order to reduce this small risk further is very unlikely to be cost-effective and could be considered overtreatment of a non-fatal disease that is sufficiently managed with local treatment. Prospective cost-effectiveness analyses have the potential to guide allocation of valuable resources for breast cancer research, and should be regularly integrated into the protocol design of large clinical trials.
Citation Format: Michael D Alvarado, Mitchell T Hayes, Rajni Sethi, Elissa Ozanne. NSABP B-43 is unlikely to produce a cost-effective treatment strategy for HER2+ DCIS [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-10-03.
Abstract P1-12-09: Possibility of GnRH agonist plus tamoxifen as an alternative treatment to AC (adriamycin plus cyclophosphamide) chemotherapy plus tamoxifen treatment in premenopausal hormone responsive HER2 negative breast cancer patients
Authors: Park Heeseung , Sohn Guiyun , Son Byung Ho , Lee Jong Won , Ahn SeiHyun 
Published: May 2015

Abstract
Background: The purpose of this study is to compare the treatment outcomes using GnRH agonist plus tamoxifen, and adriamycin and cyclophopsphamide(AC) containing chemotherapy plus tamoxifen in hormone responsive premenopausal node negative breast cancer patients.
Methods: Total 1027 premenopausal women with node negative, hormone receptor positive, Her-2 negative breast cancer were included in this retrospective cohort study. 595 patients (57.9%) were treated with GnRH agonist together with tamoxifen, and 432 patients (42.1%) were treated with adriamycin and cyclophsophamide containing chemotherapy with tamoxifen.
Results: A median follow up period was81 months. In pT1 disease, 7 year DFS (disease free survival)was 98.9% for GnRH agonist plus tamoxifen group and 97.4% for chemotherapy plus tamoxifen group, and in pT2 disease, 7 year DSS was 99.1% for GnRH agonist plus tamoxifen group, and 96.9% for chemotherapy plus tamoxifen groupwith nostatisticalsignificance (p=0.252 & 0.230).In pT1 disease, 7 year RFS was 95.4% for GnRH agonist plus tamoxifen group and 92.9% for chemotherapy plus tamoxifen group, and in pT2 disease, 7 year RFS was 91.6% for GnRH agonist plus tamoxifen group, and 91.7% for chemotherapy plus tamoxifen group with no statistical difference between two treatment groups (p=0.353 & 0.836). In subgroup analysis, ER+/PR+ patients and patientsyounger than 40 years old showed slightly better survival inGnRHagnonist plus tamoxifen group when compared to chemotherapy plus tamoxifen group with p-value of 0.046 & 0.018.
Conclusion: Adding GnRH agonist to tamoxifen is reasonable alternative to adding AC chemotherapy to tamoxifen in premenopausal luminal type node negative breast cancer patients.
Citation Format: Heeseung Park, Guiyun Sohn, Byung Ho Son, Jong Won Lee, SeiHyun Ahn. Possibility of GnRH agonist plus tamoxifen as an alternative treatment to AC (adriamycin plus cyclophosphamide) chemotherapy plus tamoxifen treatment in premenopausal hormone responsive HER2 negative breast cancer patients [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-12-09.
Abstract P2-01-16: Role of 18 FDG PET/CT in axillary staging in early breast cancer
Authors: Noblia Cristina , Azar Eugenia , Mansilla Dolores , Osorio Amilcar , Armanasco Eduardo , Montoya Diana , Ipiña Martin , Berman Gaston , Gonzalez Eduardo , Gonzalez Christian , Bruno Gabriel , Parma Patricia , Pulero Carla , Alvarez Ana 
Published: May 2015

Abstract
OBJETIVE To evaluate the 18F-FDG PET/CT capacity for the detection of axillary metastases and compare results with sentinel lymph node biopsy (SLNB).MATERIAL AND METHODS: 99 female patients with clinical T1T2N0 breast cancer were included. Patients with recent breast or axillary surgery, T3T4 disease, ductal carcinoma in situ, inflammatory carcinoma, uncontrolled diabetes mellitus and pregnant or lactation patients were excluded. Pre-operative FDG PET-CT was performed 15 days before surgery, SLNB took place with the combined method (radioisotopes and patent blue). Pearson and Spearman correlation test were used to evaluate association of main variables with a significance level (p) of 0.05.RESULTS: Breast PET-CT results: 80 positive PET/CT. Negative PET/ CT in 19 patients (4invasive lobular carcinoma, 7 tumors &lt;7mm) Sensitivity 81%, specificity 100%.97 patients were operated (2 were stage IV with no surgery criteria). We found significant correlation of the FDG tumor uptake (SUV) with tumor size (p&lt; 0.0001), histological grade (p&lt; 0.009), nuclear grade (p&lt;0.001), mitotic grade (p&lt; 0.007) and Ki 67 (p&lt; 0.0001).In all cases the correlation was positive.There was no correlation with hormonal receptors rate.Axillary PET CT results: positive PET/CT in 16 patients (16%). Of this 6 SNLB were negative (FPR= 9%). Specificity 91%, PET /CT were negative in 81 patients (84%), 17 had axillary metastases(5 micrometastases, 2 isolated tumor cells and 2 lobular carcinoma).Sensitivity:37%.FNR=63%. Correlation of histopatological axillary metastases was positive with breast tumor SUV (P&lt;0.0002) and tumor size (p&lt;0.01), but was not significant with histological, nuclear and mitotic grade, Ki 67,hormonal receptor rate and molecular subtype CONCLUSION: 1- PET / CT does not provide benefits for axillary staging in initial stages due to its low spatial resolution (6-8 mm) 2 –A negative axillary by PET/CT does not replace the sentinel node technique. 3 – We can suspect the presence of axillary metastases when there is an intense FDG uptake in the breast tumor.
Citation Format: Cristina Noblia, Eugenia Azar, Dolores Mansilla, Amilcar Osorio, Eduardo Armanasco, Diana Montoya, Martin Ipiña, Gaston Berman, Eduardo Gonzalez, Christian Gonzalez, Gabriel Bruno, Patricia Parma, Carla Pulero, Ana Alvarez. Role of 18 FDG PET/CT in axillary staging in early breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-01-16.
Abstract P2-01-20: The ratio and size of positive sentinel lymph nodes predicts the involvement of non-sentinel lymph nodes following completion axillary lymph node dissection
Authors: Dave Rajiv V , Chauhan Muhhamed N , Ghaus Maria , Ahmed Sana , Shapra Shiv , Marriott Joshua , Sayers Craig , Kryjak Zbigniew , Ali Deedar 
Published: May 2015

Abstract
Background: The role of Completion Axillary Lymph Node Dissection (CALND) following positive Sentinel Lymph Node Biopsy (SLNB) is being actively debated. The involvement of our unit in the POSNOC trial (which has a no-treatment arm), has prompted a review of our unit’s CALND results, in order to examine predictors of involvement of non-sentinel lymph nodes (n-SLN), to better inform our patients during recruitment.
Methods: We retrospectively analysed our experience of SNLB between July 2008 to 2013. A total of 1152 breast cancer patients underwent SLNB based on lymphoscintigraphy, intraoperative gamma probe detection, and blue dye mapping using 99mTc-nanocolloid and Patent Blue V injected peri-areola.
Results: Out of 1152 SLN biopsies performed, 224 were positive for metastatic disease. 203 patients were anaesthetically capable of progressing to CALND. On univariate analysis, involved n-SLN on CALND could not be predicted by age (&lt;50 years; 16/77 vs ≥50 years; 93/125, p=0.272), size of tumour (&lt;50mm; 44/193 and ≥50mm; 4/10, p=0.188), procedure (mastectomy; 24/93, WLE; 24/106, p=0.444), lymphovascular invasion (22/97 vs 26/106, p=0.812), number of positive SLN (≤2; 45/196, &gt;2; 3/7, p=0.213), receptor status; ER (negative; 3/13, positive 45/187, p=0.619), PR (negative; 6/28, positive 41/169, p=0.478), Her2 (negative; 43/175, positive 5/25, p=0.414), triple negative (2/8 vs 46/192, p=0.612). There was a trend toward higher incidence of positive n-SLN with increasing grade (G0-2; 28/139 vs G3; 20/64, p=0.062) and extracapsular spread (14/41 vs 32/149, p=0.073), but these did not reach statistical significance. Positive n-SLN on CALND was however predicted by macrometastases in SLN (macrometastases; 39/141 vs micrometastases; 9/62, p=0.029) and ratio of positive nodes (&lt;0.5; 18/109 vs ≥0.5; 30/94, p=0.008). There were 4/224 recurrences (3 distant metastases and 1 loco-regional), which were not predicted by any of the clinicopathological variables investigated. 3 patients who recurred only had one positive node on SLNB.
Conclusion
In our series of more than 200 SLNB, a ratio of &gt;0.5 positive SLN yield and presence of macrometastases in positive SLN, were associated with positive n-SLN on CALND.
Citation Format: Rajiv V Dave, Muhhamed N Chauhan, Maria Ghaus, Sana Ahmed, Shiv Shapra, Joshua Marriott, Craig Sayers, Zbigniew Kryjak, Deedar Ali. The ratio and size of positive sentinel lymph nodes predicts the involvement of non-sentinel lymph nodes following completion axillary lymph node dissection [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-01-20.
Abstract P2-03-18: Discovery of novel amplified genes in primary breast cancer with copy number and gene expression analysis of whole exome and transcriptome sequencing data
Authors: Lee Eunshin , Lim Woosung , Lee Kyung-Min , Yoo Tae-kyung , Kim Jongjin , Lee Han-Byoel , Kim Yun-Gyoung , Kang YoungJoon , Kim Min Kyoon , Moon Hyeong-Gon , Noh Dong-Young , Han Wonshik Han 
Published: May 2015

Abstract
Introduction: Copy number alteration of genome is common in breast cancer and tend to have more driver role than single point mutations. Traditionally, genome-wide analysis of DNA copy number changes were done by array CGH or SNP array method. Here, we did DNA whole exome sequencing (WES) and RNA-seq using Next Generation Sequencing (NGS) technology to find common genes or chromosomal regions of which DNA copy was highly amplified and at the same time RNA expression was also upregulated.
Materials and Method: RNA and DNA were extracted fromfresh frozen tissues of 93 breast cancer patients. WES and RNA-seq were done using NGS technology (Illumina HiSeq 2000). As a control, normal DNA from all matched patients were also sequenced. GATK was used to gain mean depth and coverage data for targeted regions.CNVs were calculated with ExomeCNV, a statistical method to detect somatic CNVs using depth-of-coverage information from mapped short sequence reads.To estimate expression levels, the relative transcript abundances were measured in FPKM using Cufflinks.
Results and Discussion: DNA of 1,737 genes were highly amplified (log R&gt;1.0) in two or more samples. The two most commonly amplified chromosomes were chromosome 8 and 17. We applied a cut-off for higher gene expression as relative FPKM &gt;1.5. ERBB2 amplifications and high expression were most common (21.5%) of all genes and it was in agreement withHER-2 IHC and FISH result. Among previously reported amplified genes, FGFR1 (5.4%) and PVT1 (8.6%) in chromosome 8, CCND1, PAK1 (3.2%) and EMSY (4.3%) in chromosome 11, CCNE1 (4.3%) in chromosome 19 were also identified in this study. IGF1R high amplification and expression was found in two samples, and ESR1, MDM2, KIT was found in only one sample each. We found uncommon but novel and recurrent highly amplified and expressed genes: CLK4 in 5q (3.2%), AHI/MYB in 6q (3.2%), MMP7(2.2%) andMALAT1 in 11q (1.1%), and NEK8 in 17q (4.3%) We designed FISH probe for this 5 new genes and confirmed the high amplifications in each sample with FISH. Functional study of these genes will be followed for the driver role of these genes in carcinogenesis and progression of breast cancer cells.
Citation Format: Eunshin Lee, Woosung Lim, Kyung-Min Lee, Tae-kyung Yoo, Jongjin Kim, Han-Byoel Lee, Yun-Gyoung Kim, YoungJoon Kang, Min Kyoon Kim, Hyeong-Gon Moon, Dong-Young Noh, Wonshik Han Han. Discovery of novel amplified genes in primary breast cancer with copy number and gene expression analysis of whole exome and transcriptome sequencing data [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-03-18.
Abstract P2-06-02: Breast cancer stem-like cell activity correlates with tumour progression to metastasis but not with clinical or tumour characteristics
Authors: Howell Sacha J , Alferez Denis , Spence Katherine , Eyre Rachel , Shaw Fran , Simoes Bruno , Santiago-Gomez Angelica , Bramley Maria , Absar Mohamed , Saad Zahida , Chatterjee Sumohan , Kirwan Cliona , Gandhi Ashu , Armstrong Anne C , Wardley Andrew M , Farnie Gillian , Clarke Robert B 
Published: May 2015

Abstract
Introduction: Breast cancers exhibit cellular heterogeneity, containing both stem-like and more differentiated cells. The activity of cancer stem cells (CSC) is likely to be dependent on the microenvironment or niche. Using 158 patient tumour samples, correlations between niche-independent breast CSC activity and clinical and tumour characteristics were tested.
Methods: 104 early breast cancer surgical samples and 54 unrelated metastatic samples from pleural or ascitic fluid were harvested. To test CSC activity, isolated cells were grown in both primary (formation) and secondary (self-renewal) mammosphere (MS) culture. Tumour initiating activity was also tested by transplanting breast cancer fragments or cells into the sub-cutaneous flanks of NSG mice (n=84 early and n=10 metastatic).
Results: No correlation was found between MS growth, MS formation (%), MS self-renewal (%) or in vivo tumour initiation and breast cancer sub-type, grade, node status or Nottingham prognostic index. 33% of the samples that formed MS in vitro initiated tumours in vivo while only 9% that failed to form MS initiated tumour growth. Metastatic compared to early BC samples grew MS more frequently (53/54 compared to 81/104), and had a higher primary MS formation efficiency (1% vs 0.6%; P&lt;0.001) although rates of MS self-renewal were similar. Tumour initiation in vivo was also more frequent in metastatic than early breast cancer samples (7/10 versus 25/84; P&lt;0.02).
Conclusions: In summary, niche-independent breast CSC activity measured in vitro by MS assay and in vivo by xenograft growth is not directly correlated with standard clinical parameters. However, both in vitro and in vivo CSC activity are increased in metastatic samples. These results suggest that breast CSC activity is independent of other prognostic indicators but may predict for poor outcome tumours. Relapse free survival data are maturing and will be presented with analysis of primary tumour ALDH1 expression.
Citation Format: Sacha J Howell, Denis Alferez, Katherine Spence, Rachel Eyre, Fran Shaw, Bruno Simoes, Angelica Santiago-Gomez, Maria Bramley, Mohamed Absar, Zahida Saad, Sumohan Chatterjee, Cliona Kirwan, Ashu Gandhi, Anne C Armstrong, Andrew M Wardley, Gillian Farnie, Robert B Clarke. Breast cancer stem-like cell activity correlates with tumour progression to metastasis but not with clinical or tumour characteristics [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-06-02.
Abstract P2-06-08: SIRT1 inhibitors significantly reduce cancer stem cells and block epithelial mesenchymal transformation in breast cancer cells
Authors: Zhang Songlin , Li Min , Guan Baoxiang , Brown Robert 
Published: May 2015

Abstract
Breast cancer stem cells are contribute to distance metastasis, breast cancer recurrence and drug resistance. SIRT1, a nicotinamide adenine dinucleotide (NAD+)-dependent histone deacetylase, play significant role in DNA repair, cell survival, stem cells and epigenetic modification. SIRT1 has been related to cancer stem cells in chronic myelogenous leukemia. In this study, we investigate the role of SIRT1 in breast cancer stem cells.
SIRT1 inhibitors cambinol and Ex527 are used for treatment in several breast cancer cell lines, including T47D, TB549, MDA-MB-231 and MDA-MB-468. Stem cell markers, SOX-2 and Nanog, are significantly decreased in SIRT1 inhibitor treated cancer cells by qRT-PCR and western blot in T47D cell line. The ALDH positive cells in MDA-MB-231 cell line are significant reduced from 29% to 3.2% with Adeflour assay, and the CD44 expression is significantly reduced in CD44/CD24 flow cytometry analysis. Using qRT-PCR, SIRT1 inhibitors significantly down regulate vimentin (-3.7 folds), N-cadherin and smooth muscle actin (-2.7 folds) and up regulate the gene of E-cadherin, indicating SIRT1 inhibitors can block the epithelial mesenchymal transformation (EMT) of breast cancer. SIRT1 inhibitors can significantly (40-50%) block the cancer cell invasion and migration in several triple negative breast cancer cell lines. SIRT1 inhibitors can inhibit cell proliferation on all tested breast cancer cell lines, and can induce significant cell apoptosis in T47D cells. In xenograft tumor study, SIRT1 inhibitor cambinol can significantly reduce tumor growth and inhibit tumor metastasis.
The molecular mechanism of SIRT1 inhibitors in blocking EMT and reducing cancer stem cells is likely associated with blocking the Wnt pathway. Several down stream target genes of Wnt pathway, such as cyclin D1, c-Myc and c-Jun, are significantly down regulated after using SIRT1 inhibitor cambinol, and the changes are more significant in TGF-beta stimulated cancer cells. Beta-catenin is significantly reduced including the active beta-catenin, and the decreasing beta-catenin protein may be related to the decreased Dvl proteins.
In summary, our study demonstrated that SIRT1 inhibitors can reduce breast cancer stem cell population in several cancer cell lines, block epithelial mesenchymal transformation, and inhibit breast cancer cell invasion and metastasis. SIRT1 inhibitors appear to inhibit Wnt pathway in cancer cells to block EMT and affect cancer stem cells.
Citation Format: Songlin Zhang, Min Li, Baoxiang Guan, Robert Brown. SIRT1 inhibitors significantly reduce cancer stem cells and block epithelial mesenchymal transformation in breast cancer cells [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-06-08.