bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract GS5-01: Appropriate margins for breast conserving surgery in patients with early stage breast cancer: A meta-analysis
Authors: Shah C , Verma V , Sayles H , Recht A , Vicini F 
Published: February 2018

Abstract
Background: Significant controversy exists regarding the appropriate minimum tumor-free margin width for patients undergoing breast-conserving therapy. The SSO-ASTRO guidelines recommend 'no ink on tumor' based upon a meta-analysis of 33 studies, but this had significant limitations. In order to address these concerns, a meta-analysis of all available data (using 31 of the initial studies) was performed but employing stricter criteria for acceptability and quality of evaluable studies.
Methods: Study eligibility criteria were: (1) minimum follow-up of 50 months; (2) explicit pathologic criteria for defining margins; and (3) consistent endpoints associated with local recurrence. The compiled studies were analyzed using generalized linear mixed models for the outcome of local recurrence, with random effects for study and fixed effects for various patient and study characteristics.
Results: The analysis incorporated 38 studies, which included 55,302 patients treated from 1968-2010. Two of the previous studies were excluded (one because of short follow-up, and the second because it was updated) with seven new studies added from the previous meta-analysis including an update of a previously included analysis. Median follow-up was 7.2 years. The median age of the cohort was 55 years, 74% of patients had T1 tumors, and 72% were node negative. The crude rate of local recurrence for patients with positive margins was 10.3%, compared to 3.8% for those with negative margins defined as no tumor on ink or wider (p&lt;0.001). The crude rates of local recurrence decreased as the margin distance increased: 7.2% for patients with margins &gt;0-&lt;2 mm, 3.6% for margins of 2-5 mm (3.6%), and 3.2% for margins wider than 5 mm (p&lt;0.001 for each). Use of endocrine therapy and increasing median study year were associated with a reduction in local recurrence in univariate models but not in multivariable analyses.
Conclusions: The current meta-analysis indicates that having margin widths 2 mm or greater is associated with a lower risk of ipsilateral breast failure than narrower but uninvolved margins. It therefore fails to confirm that 'no-tumor on ink' is optimal. Further analyses are needed to clarify this issue, particularly to identify the critical minimum tumor-free margin for different patient subgroups.
Citation Format: Shah C, Verma V, Sayles H, Recht A, Vicini F. Appropriate margins for breast conserving surgery in patients with early stage breast cancer: A meta-analysis [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr GS5-01.
Abstract MS1-1: Targeting DNA repair deficiency in triple negative breast cancers (TNBC) with G-quadruplex stabilisers
Authors: Aparicio S 
Published: February 2018

Abstract
Triple negative breast cancers (TNBC) represent a heterogeneous group of patients where pathway targeted interventions are lacking. We have recently identified new subgroups of TNBC tumours based on patterns of genomic instability, suggesting that deficiencies in DNA repair or genome maintenance could be exploited in specific subgroups of TNBC patients. We recently discovered synthetic lethal activity for small molecules that bind and stabilise G-quadruplex (G4) structures in the human genome. Stabilized G4 structures are considered "at risk" during DNA replication, leading to single strand and double strand breaks in the absence of DNA repair. This has specific application in cancers with DNA repair deficiency. We have shown that loss of homologous recombination repair capacity in breast cancers is associated with ∼ 1 log order increase in sensitivity to G4 binders. Moreover this activity has been observed in platinum pre-treated tumours, and in PARP insensitive tumours. Recently through CRISPR screening approaches we have defined additional DNA repair lesions that confer synthetic lethality to G4 binders. This mechanism of G4 stabilisation is now being tested in a phase 1/2 clinical trial of CX5461 in breast cancer patients.
Citation Format: Aparicio S. Targeting DNA repair deficiency in triple negative breast cancers (TNBC) with G-quadruplex stabilisers [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr MS1-1.
Abstract MS1-2: New clinical approaches for TNBC
Authors: Telli M 
Published: February 2018

Abstract
Over the last decade, triple-negative breast cancer (TNBC) has been the subject of intense clinical investigation. Importantly, an improved understanding of the critical role of DNA damage repair deficiency in TNBC has led to effective therapeutic strategies to target BRCA1 and BRCA2 mutation-associated TNBCs with platinum chemotherapy agents and PARP inhibitors. A major area of increasing clinical relevance focuses on the treatment of BRCA1 and BRCA2 mutation-associated breast cancers after the development of resistance to platinum and PARP inhibitor therapy. Lurbinectedin, a novel marine derived DNA damaging agent, has shown activity in BRCA1 and BRCA2 mutation-associated cancers, including those with platinum resistance.
While therapeutic strategies for TNBC patients with BRCA1 and BRCA2 mutations have increased, most TNBC patients lack an underlying germline mutation in these genes and continue to have high unmet clinical need. Multiple lines of investigation are currently underway. Androgen receptor (AR) blockade has shown preliminary proof-of-concept in AR expressing TNBCs. While monotherapy with PD-1/PD-L1 checkpoint inhibitors has shown modest activity in metastatic TNBC, multiple studies are exploring the role of these agents in combination with chemotherapy, targeted therapies and other immunotherapeutic agents. Given the high prevalence of TP53 mutations in TNBC, strategies to target additional cell cycle checkpoints including ATR, ATM, Wee1 and others may hold promise. Antibody-drug conjugates targeting Trop-2, LIV-1 and GPNMB expressing TNBCs have also shown clinical activity and are advancing in clinical development.
Citation Format: Telli M. New clinical approaches for TNBC [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr MS1-2.
Abstract OT2-07-11: Ixazomib in combination with carboplatin in pretreated women with advanced triple negative breast cancer, a phase I/II trial (AGMT MBC-10 trial)
Authors: Rinnerthaler G , Gampenrieder SP , Petzer A , Pusch R , Fridrik M , Rossmann D , Balic M , Egle D , Rumpold H , Singer C , Bartsch R , Melchardt T , Ulmer H , Mlineritsch B , Greil R 
Published: February 2018

Abstract
Background: Triple-negative breast cancer (TNBC) comprises a heterogeneous group of diseases which are generally associated with a poor prognosis. Up to now, no targeted treatment beyond anti-VEGF therapy is approved for TNBC so far and cytotoxic agents are the mainstay for the treatment of advanced tumor stages. Ixazomib is a selective, and reversible inhibitor of the proteasome, which has been mainly investigated in the treatment of multiple myeloma. In a preclinical study triple-negative breast cancer cells were treated with bortezomib, a first generation proteaseome inhibitor, alone and in combination with cisplatin, which had a synergistic effect. Clinical data are available for carboplatin plus bortezomib in metastatic ovarian and lung cancers showing remarkable antitumor activity and good tolerability. Based on this rational, the MBC-10 trial will evaluate the toxicity profile and efficacy of ixazomib in combination with carboplatin in patients with advanced TNBC.
Trial Design: Patients with metastatic TNBC pretreated with at least one prior line of chemotherapy for advanced disease with a confirmed disease progression and measurable disease are eligible for this study. Patients will receive ixazomib in combination with carboplatin on days 1, 8, and 15 in a 28-day cycle. The phase I part of this study uses an alternate dose escalation accelerated titration design. After establishing the maximum tolerated dose (MTD), accrual continues to evaluate the efficacy and safety of the combination (phase II, including 41 evaluable patients). All patients will continue on study drugs until disease progression, unacceptable toxicity or discontinuation for any other reason. Primary endpoint of the phase II is overall response rate, secondary endpoints include safety profile, progression-free survival and quality of life. This trial is open for patient enrollment since November 2016 in six Austrian cancer centers. Accrual is planned to be completed within two years. ClinicalTrials.gov Identifier: NCT02993094
Citation Format: Rinnerthaler G, Gampenrieder SP, Petzer A, Pusch R, Fridrik M, Rossmann D, Balic M, Egle D, Rumpold H, Singer C, Bartsch R, Melchardt T, Ulmer H, Mlineritsch B, Greil R. Ixazomib in combination with carboplatin in pretreated women with advanced triple negative breast cancer, a phase I/II trial (AGMT MBC-10 trial) [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr OT2-07-11.
Abstract P1-01-10: Expression of adipocyte fatty acid binding protein promotes obesity-associated mammary tumor growth
Authors: Sauter ER , Li B , Hao J , Kong M 
Published: February 2018

Abstract
Background: Obesity increases the risk of many types of cancer, including breast cancer. The underlying mechanisms that drive obesity-related breast cancer remain unclear. Fatty Acid Binding Proteins (FABPs) are a family of cytosolic proteins which are organ specific and coordinate lipid transportation. Adipocyte FABP (A-FABP) is highly expressed in adipose tissues and may provide a link to obesity-associated breast cancer risk. We previously observed that A-FABP serum levels were associated with obesity, and decreased with surgically induced weight loss. In this report, we evaluate the role of A-FABP in promoting obesity-associated mammary tumor growth. Hypothesis: Deficiency of A-FABP in mice decreases obesity-associated mammary tumor progression. Methods: Weaned wild type control and A-FABP-deficient (genetically depleted A-FABP-/-) female mice (n=15/group) were randomly grouped and fed either a high fat diet (HFD) (60% fat) or a low fat diet (LFD) (10% fat). After 6 months on the diets, serum was collected from the tail vein and measured for levels of circulating A-FABP by ELISA. E0771 mammary tumor cells (0.5x106/mouse) were injected into the mammary fat pad and tumor volume measured at 3-day intervals. The student's t-test was used to compare A-FABP levels and ANOVA to compare tumor sizes in the lean and obese mice. Results: HFD-fed control mice exhibited a significant increase in body weight (31.5±2.13g) compared to LFD-fed control mice (19.86±0.36) (p&lt;0.01). Serum levels of A-FABP were correspondingly elevated in obese (104.9±8.3 ng/ml) vs. lean controls (31.8±5.4 ng/ml) (p&lt;0.01). Interestingly, although A-FABP deficient mice fed a HFD were more obese than HFD-fed control mice (final body weight 43.4g vs. 31.5 g) (p&lt;0.05), tumor growth in the A-FABP deficient mice was significantly less than in controls (p&lt;0.0001), suggesting that A-FABP expression is critical for obesity-associated mammary tumor growth. Long term tumor growth in lean A-FABP deficient vs. control mice was not significantly different. Thus, A-FABP deficiency appears to uncouple obesity and mammary tumor growth in HFD-induced obese mice. Impact: A-FABP is associated with obesity related breast/mammary cancer, and appears to be an important driver of tumor development. Downregulation of this protein may be useful to prevent and/or treat these tumors.
Citation Format: Sauter ER, Li B, Hao J, Kong M. Expression of adipocyte fatty acid binding protein promotes obesity-associated mammary tumor growth [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-01-10.
Abstract P1-02-03: The Y537S ESR1 mutation carries unique metabolomics profiling in breast cancer
Authors: Gu G , Piyarathna B , Coarfa C , Ellis L , Ando' S , Fuqua S 
Published: February 2018

Abstract
Background:
Estrogen receptor (ESR1) mutations occur at a high frequency in metastatic breast tumors in patients treated with hormonal therapy in the metastatic setting. We do not know if these mutations changed metabolomics and whether these metabolomics change could affect metastasis.
Experimental design and methods:
We generated ESR1 Y537S homozygous mutations using CRISPR Casp-9 technology. Globe metabolites screening was performed using 6550 Agilent QTOF instrument. Athymic mice were used in tumor xenograft studies. Affymetrix microarrays were performed to compare gene expression changes in Y537S mutant compared with parental cells. Enriched metabolite pathways and gene expression integrated analysis was analyzed by using online analysis tool http://www.metaboanalyst.ca.
Results:
We generated CRISPR ESR1 Y537S mutation homozygous knock-in clones in MCF-7 cells. In vivo experiments revealed that mutant cells are dominant drivers of metastasis. Transcriptome profiling revealed elevated expression of Hallmark pathways, including EMT and estrogen-regulated gene expression. We performed globe metabolites screening using MCF-7 Y537S and MCF-7 parental and identified 134 metabolites. Serum starvation media was used and estrogen was used as control for both cell lines. As we expected estrogen treatment induced metabolites changes in parental cells. However, metabolites in mutant cells were not changed significantly under estrogen treatment. Interestingly, metabolites in the mutant cells at baseline were remarkably upregulated (78 out of 134 identified total metabolites) indicating mutant cells in serum starvation condition had significantly different metabolomics compared with parental cells. Top upregulated pathways include protein biosynthesis, betaine metabolism and ammonia recycling. Integration of microarray gene expression and metabolites reviewed several metabolomics pathways significantly changed in mutant compared with parental cells including for example aminoacyl-tRNA biosynthesis, arginine and proline metabolism and alanine, aspartate and glutamate metabolism.
Conclusion: The Y537S ER mutation is a driver of distant metastasis in ER-positive breast cancer cells. Y537S ER mutant had globe changes of metabolites expression which was confirmed by integrated analysis combining microarray gene expression. The roles of these metabolites need to be studied to correlate with metastasis. Enzymes responsible for converting these metabolites changes could be served as potential therapeutic targets.
Citation Format: Gu G, Piyarathna B, Coarfa C, Ellis L, Ando' S, Fuqua S. The Y537S ESR1 mutation carries unique metabolomics profiling in breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-02-03.
Abstract P1-03-06: GNBP2 suppresses tumor growth and cancer stem cell load of triple negative breast cancer by controlling STAT3 pathway
Authors: Zhang J 
Published: February 2018

Abstract
Background: Gametogenetin binding protein 2 (GGNBP2) is encoded in human chromosome 17q12-q23, a region known as a breast and ovarian cancer susceptibility locus. GGNBP2 has a single C2H2 zinc finger and a consensus LxxLL nuclear receptor (NR) binding motif. We have reported that GGNBP2 suppresses ERα-positive breast tumorigenesis by acting as a nuclear receptor co-repressor to restrain ERα activity. However, the detailed molecular mechanisms of GGNBP2 and its role in triple negative breast cancer (TNBC) remain largely unclear.
Methods: A human breast cancer tissue array containing 138 human breast tumor tissues were utilized to examine GGNBP2 expression in breast cancer samples by IHC. To address the potential anti-breast tumor activity of GGNBP2 in vitro, we expressed exogenous GGNBP2 in TNBC cells, including MDA-MB-231 and Cal51 cell lines. Cell proliferation and cell cycle were assessed by cell growth curve/EdU assays and flow cytometry after propidium Iodide staining. Apoptosis was determined by flow cytometry after annexin V staining, by caspase 3/7 and caspase 9 activity assays. Cancer stem cell properties were determined by expression of CD44/CD24/ALDH1 markers. The levels of phosphorylated STAT3 and total STAT3 were determined by western blot. Quantitative PCR and Western blot were carried out to evaluate the effects of GGNBP2 overexpression on STAT3 target genes, CCND1, Mcl-1, survivin, bax and bim expression.
Results: GGNBP2 expression is down-regulated in TNBC cells and patient tumors and it is associated with poor patient survival. Overexpression of GGNBP2 significanly induces cell cycle G0/G1 phase arrest and apoptosis in TNBC cell lines. Expression of cancer stem cell markers also decreased in GGNBP2-overexpressed TNBC cells. GGNBP2 reduces the expression levels of CCND1, Mcl-1 and survivin, promotes the expression levels of bax and bim proteins. Importantly, overexpression of GGNBP2 inhibits STAT3 phosphorylation and STAT3 downstream garget gene expression, including CCND1, Mcl-1 and survivin.
Conclusion: GGNBP2 serves as a critical nuclear negative regulator of STAT3-mediated gene expression and tumorigenesis.
Citation Format: Zhang J. GNBP2 suppresses tumor growth and cancer stem cell load of triple negative breast cancer by controlling STAT3 pathway [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-03-06.
Abstract P1-06-12: Optimizing the use of oncotype Dx in early breast cancer
Authors: Ruiz R , Namuche F , Flores C , Aguilar A , Gomez HL 
Published: February 2018

Abstract
Background: Oncotype Dx (ODX) prognosticates the risk of recurrence and predicts the benefit of adjuvant chemotherapy in estrogen-receptor-positive breast cancer (BC). However, its cost makes it prohibitive for many health care systems. Our objective was to develop a model that uses routine clinical and pathological parameters to identify ODX high risk patients which require adjuvant chemotherapy.
Methods: We retrospectively reviewed ODX and pathology reports from 190 early BC patients treated between 2014 and 2016 in a specialized cancer center. Our population was divided into a training (n:133) and validation set (n:57). In the training set, among available clinico-pathological variables (age, T, ER, PR, Ki67, Elston-Ellis grade) a multiple linear regression model was carried out to select those significantly associated with ODX. Coefficients of statistically significant variables were used to build an equation. The equation was applied in the training set. These results were confronted to ODX categories. The best threshold for selecting high risk patients was identified in the training set and tested in the validation set.
Results: Among the tested variables, tumor size (pT), progesterone receptor (PR), Ki67 and Ellston-Ellis grade were significantly associated with ODX RS (Table 1). The linear predictor is: (0.2544 x pT) – (0.0739 x PR) + (0.0861 x Ki67) + (5.4232 x Elston grade). The threshold score for this equation was set on 14 to discriminate high from low-intermediate risk patients. The test was able to correctly classify high risk patients with a sensitivity of 78%, a specificity of 72% and a negative predictive value of 98%.
Conclusion: With further refinement ODX could be omitted in patients classified as high risk by our predictor therefore restricting and optimizing the use of ODX to a smaller population of patients. The observed ODX distribution in our patients is similar to previously reported series suggesting that this equation could be informative in similar clinical settings. Additional external testing using new datasets is ongoing.
Citation Format: Ruiz R, Namuche F, Flores C, Aguilar A, Gomez HL. Optimizing the use of oncotype Dx in early breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-06-12.
Abstract P1-07-15: Withdrawn
Authors: Desmedt C , Fornili M , Poncet C , Clatot F , Orenti A , Boracchi P , Di Leo A , Viale G , de Azambuja E , Sotiriou C , Crown J , Francis PA , Bonnefoi H , Piccart M , Biganzoli E 
Published: February 2018

Abstract
This abstract was withdrawn by the authors.
Abstract P1-07-19: Protective effect of 27-hydoxycholesterol on disease recurrence in HER2-negative luminal type of early breast cancer
Authors: Sung Hoon S , In Hae P , So-Youn J , Seeyoun L , Sun-Young K , Han-Sung K , Eun Sook L , Keun Seok L 
Published: February 2018

Abstract
Background: 27-hydoxycholesterol (27-HC) is a metabolite of cholesterol (Chol) and known as endogeneous selective estrogen receptor modulator (SERM). Laboratory researches showed high 27-HC could stimulate cancer cell proliferation and promote metastasis processes in hormone receptor positive breast cancer. However, there is no clinical data about the effect of 27-HC on disease recurrence in early breast cancer.
Methods: A total of 539 early breast cancer patients who underwent surgery at the National Cancer Center Hospital between 2001 and 2010 with the deposition of blood samples at Tumor Bank were accrued. The blood samples were taken with overnight fasting at surgery day. Serum 27-HC was analyzed by liquid chromatography–mass spectrometry (LC-MS). 27-HC and Chol were categorized into two groups (low vs high) by median, respectively.
Results : Hormone receptor was positive in 441 patients and negative in 98 while HER2 was positive in 81, negative in 325 and unknown in 133 patients. The median follow up time was 92 months (range 24 -153.7). The 27-HC (median, 115.73 ng/ml with the range of 29.36- 234.0) and Chol (median, 170.0 mg/dl with the range of 91- 290) showed weak correlation (ρ=0.24, P&lt;0.001).
While 27-HC was not significant in analysis for RFS in all cases, it showed marginal significance for RFS in the subset analysis with HER2-negative luminal breast cancer patients (HR, 0.463; 95% CI, 0.208-1.031; P = 0.059). When the patients were grouped according to 27-HC and Chol level (group27HC/Chol) in luminal subgroup, it showed a trend for increasing RFS in the order of grouplow/high , grouplow/low, grouphigh/low and grouphigh/high(Ptrend= 0.009).
Conclusion : Serum 27-HC was not associated with poor RFS. High serum 27-HC could be related to good prognosis in HER2-negative luminal type of breast cancer, which may be related to the protective effect of 27-HC from disease recurrence. Further study is warranted.
Citation Format: Sung Hoon S, In Hae P, So-Youn J, Seeyoun L, Sun-Young K, Han-Sung K, Eun Sook L, Keun Seok L. Protective effect of 27-hydoxycholesterol on disease recurrence in HER2-negative luminal type of early breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-07-19.