bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract LB-333: Antagonistic interaction effects of aspirin and folic acid on inflammatory markers
Authors: Ho Gloria Y , Xue Xiaonan , Saibil Fred , Rohan Thomas , Baron John 
Published: May 2019

Abstract
This ancillary study to the Aspirin/Folate Polyp Prevention Trial examined the effects of low dose aspirin and folic acid (FA) supplementation on reducing the levels of inflammatory markers- CRP, IL-6, and TNF-α. The Aspirin/Folate Trial was a randomized, double-blind trial of aspirin and folate to prevent recurrent colorectal adenomas. In a 3x2 factorial design, patients were randomized to receive 81 mg/d or 325 mg/d of aspirin or placebo, and to receive 1 mg/d of FA or placebo. In this ancillary study, blood samples collected at baseline and year 3 were assayed for the 3 inflammation markers. Marker levels at year 3 were analyzed by linear regression, with main effects of the randomization groups and interaction between aspirin and FA modeled as independent variables. In the FA-placebo stratum, mean CRP at year 3 decreased with increasing dosage of aspirin, and it was 0.58 μg/mL lower in the aspirin-325 mg group than aspirin-placebo group (P=0.048). However, in the FA-1 mg stratum, the aspirin-325 mg group actually had a higher mean CRP than aspirin-placebo. Similarly, among individuals not given aspirin, the FA-1 mg group had a 0.58 μg/mL reduction in mean CRP as compared to the FA-placebo group (P=0.045), but in individuals who were also given 325 mg of aspirin, mean CRP was higher in FA-1 mg than FA-placebo. Therefore, 325 mg of aspirin or FA alone decreased CRP levels, but together they attenuated the effects of each single regimen (P=0.033 for interaction). There were also antagonistic interaction effects on TNF-α (P=0.019) and the overall proinflammatory index (P=0.009) calculated by combining the levels of the 3 markers. Similar results were obtained when adjusting for other covariates, including baseline marker levels. Long-term use of low dose aspirin or FA supplementation alone has a modest anti-inflammatory effect, but the two regimens together eliminate such beneficial effects, and the mechanism needs to be elucidated.
Table 1.Geometric mean of inflammation markers at year 3 by randomization groupAspirin: PlaceboAspirin: 81 mgAspirin: 325 mgFolic Acid: PlaceboCRP (μg/mL)2.452.141.87*IL-6 (pg/mL)2.102.012.01TNF-α (pg/mL)2.161.511.63Folic Acid: 1 mgCRP (μg/mL)1.87**2.172.15IL-6 (pg/mL)1.942.112.15TNF-α (pg/mL)1.661.652.42*P=0.048, mean CRP levels between aspirin-325 mg and aspirin-placebo in the FA-placebo subgroup. **PP=0.045, mean CRP levels between FA-1 mg and FA-placebo in the aspirin-placebo subgroup.
Abstract P1-06-08: Improved endocrine therapy response prediction using a whole slide digital ER and PR staining score to assess local ER pathway activity in hormone receptor positive breast cancer patients
Authors: van Ooijen H , van Hemert F , van der Ven J , de Inda MA , Velter R , Halter D , den Biezen-Timmermans E , van Brussel A , van de Wiel P , Wimberger-Friedl R , van de Stolpe A 
Published: May 2019

Abstract
This abstract was withdrawn by the authors.
Abstract P2-01-04: Use of axillary ultrasound impacts outcome of node positive breast cancer patients
Authors: Verheuvel NC , Voogd AC , Tjan-Heijnen VCG , Roumen RMH 
Published: May 2019

Abstract
Background The Z0011 trial initiated a paradigm shift in the treatment of axillary node positive breast cancer patients. Treatment strategy, however, starts with the information gathered by the diagnostic axillary work up. This can either be done by sentinel lymph node biopsy (SLNB) or ultrasound guided lymph node biopsy (UGLNB). We examined whether there are relevant clinical and prognostic differences between patients found node positive by these two diagnostic selection processes.
Methods Patients diagnosed with invasive breast cancer in the Netherlands between January 2000 and December 2013 were studied. Patients with no clinically palpable lymphadenopathy (cN0) and node-positive disease after an axillary lymph node dissection (ALND) were included. Patients with stage IV breast cancer, with clinical stage T3-T4 breast tumor according to the TNM-classification, those treated within the neo-adjuvant setting, patients with palpable axillary nodes (cN≥1) and patients who did not undergo an ALND were excluded.
Results A total of 14,730 patients fulfilled the inclusion criteria, of whom 9,448 were included in the SLNB group and 5,282 in the UGLNB group. Patients in the UGLNB group were older at diagnosis (p&lt;0.001), had larger tumors (p&lt;0.001), a higher tumor grade (p=0.001), and were more likely to have a negative hormonal receptor status (p&lt;0.001) and to undergo a mastectomy (p&lt;0.001). Patients in the UGLNB group were also more likely to have ≥3 positive axillary lymph nodes (p&lt;0.001) and, after adjustment for these differences, had a worseoverall survival (HR=1.64; 95% CI=1.53-1.75) compared to the node-positive patients in the SLNB group.
Conclusion Our multicenter study shows that patients with a positive UGLNB have less favorable disease characteristics and a worse prognosis compared to patients with a positive SLNB. The diagnostic selection process plays an important role when axillary treatment strategies are considered. Therefore, we conclude that the conclusions of the Z0011 trial cannot (yet) be applied to patients with a positive UGLNB.
Citation Format: Verheuvel NC, Voogd AC, Tjan-Heijnen VCG, Roumen RMH. Use of axillary ultrasound impacts outcome of node positive breast cancer patients [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-01-04.
Abstract P3-13-13: Breast-conserving surgery plus hormone therapy without irradiation in elderly women with early breast cancer
Authors: Inoue H , Hirano A , Ogura K , Hattori A , Yukawa H , Sakaguchi S , Matsuoka A , Tanaka N , Kodera A , Kamimura M , Fujibayashi M , Naritaka Y , Shimizu T 
Published: May 2019

Abstract
Background
The meta-analysis of the Early Breast Cancer Trialists' Collaborative Group (EBCTCG) revealed that whole-breast irradiation after breast conserving surgery (BCS) decreased ipsilateral breast tumor recurrence (IBTR) and breast cancer-related death. However, elderly patients can find daily hospital attendance difficult, and their IBTR risk is low. A randomized control trial was performed in women aged ≥70 years with hormone-positive breast cancer to investigate the usefulness of breast-conserving therapy without irradiation (Hughes et al. N Engl J Med 2004). Since September 2001, we have offered BCS plus hormone therapy without irradiation in patients who satisfy the following criteria: age ≥60 years; pathologically node negative, hormone-positive breast cancer; a negative surgical margin; and no lymphovascular invasion. We assessed prognosis in patients who chose this option.
Patients and methods
Between September 2001 and December 2014, 219 patients met the inclusion criteria; 90 and 129 patients underwent BCS plus hormone therapy with or without irradiation, respectively. The cumulative IBTR incidence and overall survival (OS) for the groups was evaluated. A negative surgical margin was defined as a margin of ≥5 mm.
Results
The median ages at operation were 73 years (range, 60–88 years) and 65 years (range, 60–80 years) for the without and with irradiation groups, respectively (p &lt;0.001). There were no significant differences in tumor size, lymph node metastasis, or adjuvant therapy between the groups. The median follow-up duration is presently 4.6 years. IBTR was observed in 5 (3.9%) and 1 (1.1%) patient(s) in the without and with irradiation groups, respectively (p = 0.192). The 5-year IBTR cumulative incidences were 0.9% and 2.2%, and the 10-year were 6.7% and 2.2%, for the without and with irradiation groups, respectively (p = 0.390). The 5-year OS rates were 93.8% and 98.5%, and the 10-year OS rates were 89.7% and 94.0 for the without and with irradiation groups, respectively (p = 0.205).
Conclusion
BCS plus hormone therapy without irradiation in elderly patients is an appropriate option.
Citation Format: Inoue H, Hirano A, Ogura K, Hattori A, Yukawa H, Sakaguchi S, Matsuoka A, Tanaka N, Kodera A, Kamimura M, Fujibayashi M, Naritaka Y, Shimizu T. Breast-conserving surgery plus hormone therapy without irradiation in elderly women with early breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P3-13-13.
Abstract P3-14-14: Endoscopic 3D latissimus dorsi muscle harvesting for immediate breast reconstruction. Results of our 7 patients experience in Antoine Lacassagne Nice Cancer Center
Authors: Barranger E , Dejode M 
Published: May 2019

Abstract
Introduction :
The harvest of the latissimus dorsi muscle for the realization of immediate breast reconstruction induces a large dorsal scar measuring up to 20 centimeters, while only the muscle is used. We present here the results of our experience of endoscopic harvesting of the latissimus dorsi muscle using 3D technology. Our main objective is to reduce the dorsal scar and second assess the functional consequences for patients.
Methods:
Between December 1st, 2015 , and June 1st, 2016, there were 7 patients who underwent latissimus dorsi endoscopic harvesting, with 3D technology, for an immediate breast reconstruction after a skin-sparing or nipple sparing mastectomy.
Results:
4 patients had latissimus dorsi muscle with breast implant and 3 patients by latissimus dorsi muscle only. The age average was 55 years (range 45-70). The mean length of surgery was 250 minutes (range 150- 380). The mean length of hospitalization was 7 days (range 4-12 days). One patient treated for local recurrence had skin necrosis because of previous radiotherapy. Donor site seroma was the main post surgery drawback. Patients on average benefited from 3 evacuations (range 1-5) of 850ml (range 640-1270ml). Acceptance of the reconstructed breast was good in six cases, and poor in one case. Only one patient reported discomfort at the donor site 1 month after surgery.
Conclusion:
The endoscopic 3D latissimus dorsi flap harvesting allows to reduce donor site scar. There is no significant difference concerning complications or post-operative pain and functional discomfort between the endoscopic and classic harvesting procedure.
Citation Format: Barranger E, Dejode M. Endoscopic 3D latissimus dorsi muscle harvesting for immediate breast reconstruction. Results of our 7 patients experience in Antoine Lacassagne Nice Cancer Center [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P3-14-14.
Abstract P4-15-02: Investigating the use estrogen receptor β agonists in the prevention of breast cancer using a transgenic mouse model
Authors: Samayoa C , Krishnegowda NK , Vadlamudi RK , Tekmal RR 
Published: May 2019

Abstract
Breast cancer is the most common cancer among women worldwide. In the United States, 1 in 8 women will develop breast cancer during her lifetime, and in 2016 over 240,000 new cases will be diagnosed. Incidence rates differ by geographic location, with women living in Asia having the lowest rates. However, after migrating to the U.S and adopting a western diet their rates increase. This highlights the importance of lifestyle, including diet, in modulating breast cancer risk. Soy has been previously implicated as the dietary component contributing to the reduced breast cancer rates in Asian women. Compounds that can selectively activate Estrogen Receptor β have been identified in plants, including soy. Given the tumor-suppressive properties of ERβ, it may be possible to use these agonists in the chemoprevention of breast cancer.
The objective of this study was to investigate the utility of using ERβ agonists in the prevention of breast cancer using a transgenic mouse model. MMTV-HER2/neu mice develop premalignant lesions at 4-5 months, and tumors starting at month 7 due to overexpression of the Her2/neu proto-oncogene. MMTV-HER2/neu mice were treated with 2 different ERβ agonists, S-equol or LY500307, for 3 months and evaluated for branching, hyperplasia and differential gene expression. When compared to controls, ERβ agonist-treated mice exhibited a significant decrease in branching and ductal hyperplasia, with no change in body weight. Differential gene expression analysis revealed 218 modified genes in response to S-equol treatment, and 258 genes modified by LY500307 treatment, with an overlap of 36 genes. Pathway analysis identified an enrichment for chemokines signaling pathways, particularly TNF, in the reversal of hyperbranching resulting from treatment with ERβ agonists.
Although previous studies have demonstrated crosstalk between ER's non-genomic signaling and growth factor signal transductions pathway, this is the first study to demonstrate the impact of ERβ activation on HER2/neu mediated pre-neoplastic changes. Our study suggest that ER β agonist treatment may be a valuable therapeutic option for the chemoprevention of breast cancer in women at increased risk.
Citation Format: Samayoa C, Krishnegowda NK, Vadlamudi RK, Tekmal RR. Investigating the use estrogen receptor β agonists in the prevention of breast cancer using a transgenic mouse model [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-15-02.
Abstract P6-01-04: Evolutionary analyses of matched primary and metastatic breast cancer reveal both linear and parallel progression with lack of axillary lymph node involvement
Authors: Ullah I , Muralidharan KG , Alkodsi A , Kjällquist U , Stålhammar G , Lövrot J , Martinez NF , Lagergren J , Hautaniemi S , Hartman J , Bergh J 
Published: May 2019

Abstract
This abstract was withdrawn by the authors.
Abstract BL1: Modeling Immune Response: Lessons Learned from Mouse Models of Cancer Development
Authors: Coussens L 
Published: May 2019

Abstract
The concept that leukocytes are critical components of solid tumors is now generally accepted, however, their role(s) in regulating aspects of cancer progression, and/or response to cytotoxic, targeted and/or immune therapy is only beginning to be understood. Utilizing de novo mouse models of mammary tumor development, we now appreciate that CD4+ T lymphocytes differentially regulate myeloid cell recruitment, activation and effector function, and in turn, activated tumor-infiltrating myeloid cells foster malignancy and repress anti-tumor immunity by a diversity of mechanisms. Treatment of tumor-bearing mice with therapeutic agents disrupting lymphocyte-myeloid interactions, myeloid activation, or myeloid functionality generally slow primary tumor growth kinetics when combined with cytotoxic therapy; however, their impact on metastases is variable. Similar to organ-specific regulatory programs co-opted to foster primary tumor growth, regulation of metastatic seeding and outgrowth is also regulated by tissue- and organ-specific mechanisms. Based on this, it stands to reason that therapeutic strategies may not be efficacious in both primary and metastatic locations. To be presented will be our recent insights into organ-specific regulation of primary and metastatic mammary cancer development by adaptive and innate immune cells regulating pro- and/or anti-tumor immunity, and new studies evaluating how attenuating protumor properties of select lymphoid and myeloid cells can be exploited to enhance therapeutic responses to cytotoxic and immune-based therapy.
LMC acknowledges generous support from the NIH / NCI, the Department of Defense Breast Cancer Research Program Era of Hope Scholar Expansion Award, Susan G. Komen Foundation, the Breast Cancer Research Foundation, the Brenden-Colson Center for Pancreatic Health, and a Stand Up To Cancer – Lustgarten Foundation Pancreatic Cancer Convergence Dream Team Translational Research Grant.
Citation Format: Coussens L. Modeling Immune Response: Lessons Learned from Mouse Models of Cancer Development [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr BL1.
Abstract BS1-3: New insights into early-stage bone colonization of disseminated breast cancer cells
Authors: Zhang X 
Published: May 2019

Abstract
The fate of disseminated tumor cells is heavily influenced by their microenvironment niche. The osteogenic niche promotes cancer cell proliferation and bone metastasis progression. We investigated the underlying mechanisms using a variety of pre-clinical models and bioinformatics analyses of clinical data. We find that disseminated tumor cells may follow a “migration-by-tethering” mechanism to reach the osteogenic niche and establish tight direct interaction with the osteogenic cells. This interaction in turn profoundly alters signaling cascades in bone micrometastases. Heterotypic adherens junctions between cancer cells and osteogenic cells induce activation of the mTOR signaling. Gap junctions mediate calcium flux from osteogenic cells to cancer cells, and activate the calcium signaling. Upon the development of these junctions, ER signaling in ER+ breast cancer cells is dramatically suppressed, conferring endocrine independence. These alterations lead to unexpected therapeutic resistance and sensitivity, which were elucidated in part by a novel ex vivo bone-in-culture array system. Our findings, together with others in the literature, demonstrate the importance of considering microenvironment effects in metastatic therapies, and suggest novel therapeutic strategies to eliminate micrometastases.
Citation Format: Zhang X. New insights into early-stage bone colonization of disseminated breast cancer cells [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr BS1-3.
Abstract ES1-3: Advanced HER2-positive breast cancer: Overcoming treatment resistance
Authors: Rimawi M 
Published: May 2019

Abstract
For two decades, HER2 has been an attractive therapeutic target. Anti-HER2 agents have transformed the care of HER2+ breast cancer and greatly improved its outcomes. However, treatment resistance remains a considerable clinical problem, and some patients still recur and progress despite optimal treatment. A particular challenge in advanced HER2+ breast cancer remains to be CNS metastasis. Special attention needs to be given to this devastating event given its serious sequelae, and its prevalence among patients battling this disease. As more agents are being approved in the early setting, improving outcomes in this setting, patients who suffer a recurrence may have more limited options and more resistant disease.
The good news is that there is a number of anti-HER2 agents being explore in the advanced setting of HER2+ breast cancer. They fit into three major categories: new or optimized monoclonal antibodies, antibody-drug conjugates, and tyrosine kinase inhibitors. There is also great interest in studying other classes of agents in combination with anti-HER2 treatment, like immune-oncology agents, in this space.
The plethora of agents being developed in this setting highlights the importance to understand more about potential mechanisms of resistance. This will help guide development strategies, deliver tailored treatment approaches, and design more effective agents and regimen.
Resistance may be the end result of many possible molecular changes that mediate its emergence, and a variety of strategies are needed to elucidate them. That includes comprehensive in depth molecular profiling, as well as functional validation of detected alterations. Moreover, each tumor may have many underlying molecular changes in different cell sub-populations.
It is therefore mandatory that development strategies for new agents and combinations should rely on clinical and biologic factors to help improve outcomes for patients with advanced HER2+ breast cancer.
Citation Format: Rimawi M. Advanced HER2-positive breast cancer: Overcoming treatment resistance [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr ES1-3.
Abstract ES10-2: Mining noncoding mutations for drivers of development in ER alpha-positive breast cancer
Authors: Lupien M 
Published: May 2019

Abstract
Large-scale analysis of whole genome sequencing of breast tumors has identified thousands of genetic alterations, such as single-nucleotide variants (SNVs), outside of gene coding sequences. Delineating the functional impact of these noncoding SNVs is challenging, limiting their inclusion in precision genomics medicine pipelines. Pan-cancer attempts to detect evidence for positive selection within individual CREs identified promoters of a limited number of genes such as TERT. By considering the enrichment of noncoding mutations in cistromes as opposed to individual CREs, we identify the enrichment of noncoding SNVs in cistromes of breast cancer driver transcription factors, including FOXA1. This parallels enrichment of breast cancer genetic predispositions over these transcription factor cistromes. Furthermore, somatic SNVs accumulate in the regulatory plexus of some of these driver transcription factors providing evidence for a multi-targeted approach to disrupt their activity in breast cancer. In conclusion, our results support a functional impact of somatic SNVs converging on the cistrome of driver transcription factors in breast cancer. Altogether, we show how to interrogate noncoding SNVs to delineate the oncogenic determinants of breast cancer to be considered for therapeutic intervention.
Citation Format: Lupien M. Mining noncoding mutations for drivers of development in ER alpha-positive breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr ES10-2.