bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract PD8-04: Neoadjuvant chemotherapy for breast cancer: Nodal downstaging is highly correlated with pathological complete response
Authors: Blumencranz P , Habibi M , Treece T , Blumencranz L , Yoder E , Audeh W , Carter E , McNaughton L , Roussos J , Shivers S , Acs G , Cox C , MINT Investigators Group 
Published: May 2019

Abstract
Background: Neoadjuvant chemotherapy (NAC) is employed in patients with larger tumors to attempt to downstage locally advanced cancers to allow breast conservation and to assess in vivo tumor response. The Multi-Institutional Neoadjuvant Therapy MammaPrint Project I (MINT) study asked a secondary question of whether complete nodal downstaging could also be achieved with NAC.
Methods: This analysis included 147 eligible invasive breast cancer patients with high tumor burdens, classified as cT2-4N0-3M0 (T2 greater than 3.5cm if N0). Patients who had a positive core biopsy and/or fine needle aspiration (FNA) on an axillary node prior to starting NAC were included in this analysis. Those who had a surgical sentinel lymph node biopsy were not included. Nodal involvement was established following neoadjuvant treatment by axillary lymph node dissection (ALND).
Results: This population was 54% postmenopausal, average age 53 yrs (range 25 to 80 yrs). Tumor characteristics were 91% invasive ductal carcinoma; 65% T2, 29% T3, 6% T4; 87% LN1, 13% LN2-3; 3% low grade, 38% intermediate grade, 59% high grade; 65% ER-positive, 49% PR-positive, and 28% HER2-positive by immunohistochemistry; 84% High Risk (HR) and 16% Low Risk (LR) by MammaPrint (MP). After NAC, 45% (66/147) of these LN-positive patients were down-staged to ypN0 and also achieved a complete pathological response in the primary tumor. The potential for down-staging was inversely-related to tumor burden, where 47% (60/128) of N1, 35% (6/17) of N2, and 0% (0/2) of N3 patients were down-staged to ypN0. There were 3 patients who were down-staged (2 N2 to N1, and 1 N3 to N2), but not to ypN0. At surgery, 34% (44/128) of patients had no change, and 19% (24/129) progressed in LN staging.
Pre vs Post NAC Nodal StagePre NAC Nodal StageypN0ypN1ypN2ypN3TotalcN16044222128cN2626317cN3 112Total6646296147
Conclusions: We confirmed that upon achieving a complete response of the primary tumor that there was also a pathologic complete response in the LN. About 53% of patients had no change or progression of LN involvement following NAC.
Citation Format: Blumencranz P, Habibi M, Treece T, Blumencranz L, Yoder E, Audeh W, Carter E, McNaughton L, Roussos J, Shivers S, Acs G, Cox C, MINT Investigators Group. Neoadjuvant chemotherapy for breast cancer: Nodal downstaging is highly correlated with pathological complete response [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 PD8-04.
Abstract PD8-06: Fluorescence guided breast conserving surgery
Authors: Sharma CK , Ranjan P , Qaiser D , Dhar A , Srivastava A , Kataria K 
Published: May 2019

Abstract
Background. Palpation guided breast conserving surgery for breast cancer is associated with tumor involved margins in up to 41% of cases. Ultrasound guided breast conserving surgery and frozen section biopsy result in a significant reduction in margin positivity. However, intra-operative USG and Frozen section biopsy are not widely available. We aimed to find a simple and effective technique for intra-operative margin assessment during breast conserving surgery.
Hypothesis. Intravenously injected Fluorescein reaches tumor tissue in high concentration due to increased tumor blood flow and increased capillary permeability which can be detected by blue light (494 nm).
Objective. To find diagnostic accuracy of fluorescence guided identification of tumor margins during breast conserving surgery.
Methods. A total of 60 patients with T1–T2 invasive breast cancer who underwent breast conserving surgery at AIIMS, New Delhi between March, 2016 to Feb, 2018 were included. Each patient received 2 ml of intra-venous 20% Fluorescein sodium just before skin incision. Breast conserving surgery was performed under USG guidance. Specimen was bisected and examined under blue light. Fluorescent tumor margins were identified and six biopsies taken from non-fluorescent area 5mm outside from fluorescent tumor margins at 2,4,6,8,10 and 12 o'clock position. The involvement of USG guided margin was compared with Fluorescence guided margins on histopathology.
Results. Mean age of the patient was 51.2 (SD=6.4) years. Fourteen patients (20.3 %) had T1 tumors while 46 patients(69.7%) had T2 tumors. Axillary nodes were involved in 19 patients (20.1%) and all underwent axillary node dissection. Eight patients (13.3%) received NACT. Fluorescent margins in two (3.3%) out of 60 patients were involved by tumor while USG guided margins in all the 60 patients were free. The specificity of fluorescence in identifying uninvolved tumor margins during breast conserving surgery is 96.7%.
No patient developed adverse drug reactions.
Conclusion. The fluorescence identifies tumor free margins with 96.7% accuracy. It is simple, effective and affordable method of identifying margin positivity in breast conservation surgery.
Citation Format: Sharma CK, Ranjan P, Qaiser D, Dhar A, Srivastava A, Kataria K. Fluorescence guided breast conserving surgery [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 PD8-06.
Abstract PL1: Breast Tumor Evolution and Intratumor Heterogeneity - Insights from Single Cell Genomics
Authors: Navin N 
Published: May 2019

Abstract
Breast tumors evolve from single cells in the ducts and acquire mutations leading to divergent lineages and intratumor heterogeneity in invasive cancers. To understand the genomic evolution of breast cancers during complex evolutionary processes including initiation, invasion and therapeutic resistance we have developed single cell sequencing (SCS) methods. I will discuss our efforts in applying SCS methods to study invasion in 10 premalignant breast cancer patients with ductal-carcinoma-in-situ (DCIS), which led to a discovery of early punctuated copy number evolution in the ducts and multi-clonal invasion. I will also discuss our work in applying both single cell DNA and RNA sequencing methods to study chemoresistance evolution in 20 triple-negative breast cancer patients using longitudinal samples, which identified an adaptive genomic evolution and acquired transcriptional reprogramming during resistance. Finally I will present unpublished work on our efforts to develop a 'Human Breast Cell Atlas' of cell types and cell states (transcriptional programs) of normal cell types, and recent work on delineating copy number evolution in BRCA-positive breast cancer patients.
Citation Format: Navin N. Breast Tumor Evolution and Intratumor Heterogeneity - Insights from Single Cell Genomics [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 PL1.
Abstract A08: CCL2-induced chemokine cascade promotes breast cancer metastasis via retention of metastasis-associated macrophages
Authors: Kitamura Takanori , Pollard Jeffrey W. 
Published: May 2019

Abstract
This abstract is being presented as a short talk in the scientific program. A full abstract is printed in the Proffered Abstracts section (PR17) of the Conference Proceedings.
Citation Format: Takanori Kitamura, Jeffrey W. Pollard. CCL2-induced chemokine cascade promotes breast cancer metastasis via retention of metastasis-associated macrophages. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Metastasis; 2015 Nov 30-Dec 3; Austin, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(7 Suppl):Abstract nr A08.
Abstract A14: A cholesterol metabolite acts on the host to increase breast cancer metastasis
Authors: Baek Amy Eun Joo , Nelson Erik Russell 
Published: May 2019

Abstract
With a woman's lifetime risk of developing invasive breast cancer at one in eight, breast cancer remains the most common cancer and the second leading cause of cancer death in women. Despite the success of frontline endocrine therapies, relapse with resistant metastatic disease is common, and triple negative disease remains without a targeted therapy. Importantly, breast cancer associated mortality is most often due to the metastatic spread of the disease. Therefore, there continues to be a need for studies that may lead to the development of new chemopreventive strategies and/or lifestyle changes that reduce breast cancer metastasis. In this regard, both obesity and elevated cholesterol are risk factors for metastatic relapse, while patients receiving cholesterol-lowering drugs such as HMG-CoA reductase inhibitors (statins) display an increased relapse-free survival time. Therefore, clinical observations strongly implicate cholesterol in the metastatic progression of, although the underlying mechanisms remain unknown. Thus, we initiated a series of studies to evaluate the mechanisms by which cholesterol promotes breast cancer metastasis. Using murine models of mammary cancer, we find that elevated cholesterol does indeed increase metastasis. Further, statins attenuated the metastatic effects of a high fat diet, implicating cholesterol as a primary mediator of this pathology. Importantly, the pro-metastatic effects of cholesterol required the presence of CYP27A1, the enzyme responsible for its conversion to 27-hydroxycholesterol (27HC). We have recently shown that 27HC is an endogenous ligand for the both the estrogen receptors (ERs) and liver X receptors (LXRs). Interestingly, however, the metastatic effects of 27HC were also prevalent in ER-negative models. While LXR activation did have a modest effect on epithelial to mesenchymal transition (EMT), we find that the robust pro-metastatic effects of 27HC are mediated in a cancer cell-extrinsic manner. Specifically, we find that 27HC alters myeloid cell recruitment and function at distal metastatic sites, and thereby facilitates cancer cell colonization and growth by modulating the host environment. In summary, our data strongly suggest that by altering the host immune system, 27HC is the down-stream mediator of the effects of obesity and cholesterol on breast cancer metastasis. These results provide additional support for development of specific CYP27A1 inhibitors and immune-modulatory therapies for the prevention and treatment of breast cancer metastasis.
This work was supported by an NIH-NCI grant to ERN (4R00CA172357-03).
Citation Format: Amy Eun Joo Baek, Erik Russell Nelson. A cholesterol metabolite acts on the host to increase breast cancer metastasis. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Metastasis; 2015 Nov 30-Dec 3; Austin, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(7 Suppl):Abstract nr A14.
Abstract A19: Pulmonary microthrombosis enhances tumorigenesis via myeloid hypoxia-inducible factors
Authors: Evans Colin E. , Palazon Asis , Sim Jingwei , Tyrakis Petros A. , Bendahl Par-Ola , Belting Mattias , Rundqvist Helene , Branco Cristina , Johnson Randall S. 
Published: May 2019

Abstract
Thrombosis causes local blood flow restriction and tissue hypoxia, and both of these are associated with tumor cell metastasis. To better understand the regulation of thrombosis-induced metastasis, we created a model incorporating elements of both processes. Controlled induction of pulmonary microthrombosis caused an increase in expression of first hypoxia-inducible factor (HIF)1α, and subsequently HIF2α. Induction of thrombosis before the introduction of tumor cells to venous circulation had no effect on pulmonary tumor number or size; but thrombosis at the time of tumor cell seeding increased number and size of tumors in the lung. Thrombosis on the day after seeding of tumor cells caused an even greater increase in tumor number and size, and this effect persisted until even when thrombosis was induced five days after the introduction of tumor cells into the blood. Experiments on myeloid HIF1α or HIF2α knockout mice demonstrated that loss of either HIF1α or HIF2α eliminated the advantage given to pulmonary tumorigenesis by thrombotic insult. In primary human tumours, markers of thrombosis were positively correlated with expression of the 2 HIFα isoforms. These data demonstrate the importance of microthrombosis in a novel model of metastasis and the essential role of the myeloid cell-specific HIFα response in mediating this process.
Citation Format: Colin E. Evans, Asis Palazon, Jingwei Sim, Petros A. Tyrakis, Par-Ola Bendahl, Mattias Belting, Helene Rundqvist, Cristina Branco, Randall S. Johnson. Pulmonary microthrombosis enhances tumorigenesis via myeloid hypoxia-inducible factors. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Metastasis; 2015 Nov 30-Dec 3; Austin, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(7 Suppl):Abstract nr A19.
Abstract A20: Mammary tumor-derived CCL2 enhances pro-metastatic systemic inflammation through upregulation of macrophage-derived IL1beta
Authors: Kersten Kelly , Coffelt Seth B. , Verstegen Niels J. , Vrijland Kim , Ciampricotti Metamia , Doornebal Chris W. , Hau Cheei-Sing , Doshi Parul , Visser Karin E. de 
Published: May 2019

Abstract
Metastatic breast cancer remains a major cause of cancer-related death among women. Metastasis is regulated by extensive crosstalk between cancer cells and immune cells. Besides the onset of a local inflammatory microenvironment, tumors frequently induce a systemic inflammatory state characterized by the release of various cytokines, chemokines and growth factors to mobilize myeloid cells that support metastasis, emphasizing the notion that cancer should be regarded as a systemic disease. Utilizing the K14cre;Cdh1F/F;Trp53F/F (KEP) conditional mouse model of metastatic breast cancer, we have recently unraveled a novel mechanistic link between mammary tumor-induced IL17-producing gamma delta T cells, systemic expansion of immunosuppressive neutrophils and metastasis formation. We identified tumor-derived IL1beta as one of the drivers of this cascade by inducing IL17 release from gamma delta T cells. However, it remains unclear how other inflammatory mediators are involved in this systemic inflammatory cascade. In the current study, we identified the pro-inflammatory cytokine CCL2 as a key regulator of the gamma delta T cell IL17 neutrophil axis. CCL2 blockade resulted in reduced IL17-production by gamma delta T cells, decreased systemic neutrophil accumulation and enhanced CD8+ T cell activity. We show that activation of this cascade relies on CCL2-mediated release of IL1beta from CCR2+ tumor-associated macrophages. These results indicate that CCL2, via IL1beta, acts as a key player in regulating the pro-metastatic gamma delta T cell IL17 neutrophil systemic inflammatory cascade and might be an interesting candidate for therapeutic targeting.
Citation Format: Kelly Kersten, Seth B. Coffelt, Niels J. Verstegen, Kim Vrijland, Metamia Ciampricotti, Chris W. Doornebal, Cheei-Sing Hau, Parul Doshi, Karin E. de Visser. Mammary tumor-derived CCL2 enhances pro-metastatic systemic inflammation through upregulation of macrophage-derived IL1beta. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Metastasis; 2015 Nov 30-Dec 3; Austin, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(7 Suppl):Abstract nr A20.
Abstract A22: The effects of Lipocalin-2 in the early stages of colorectal cancer metastasis
Authors: Hughes Daniel , Davis Celestia , Zhang Yu , Bonaparte John , Pena Maria 
Published: May 2019

Abstract
Colorectal cancer (CRC) is the second leading cause of cancer deaths in the United States. When diagnosed at an early, localized stage, the five year survival rate is approximately 90%; however, when patients are diagnosed at the metastatic stage, this drops to 12%. Metastasis, the spread of cancer cells from the primary tumor to a distant organ, is the primary cause of death in cancer patients. In CRC, metastasis is typically found in the liver, asymptomatic, and often detected at the final stage when therapeutic options are few. The genetic and cellular mechanisms driving the early stages of metastasis are still poorly understood. Recent studies have shown that prior to the arrival of cancer cells at the secondary organ, molecular signals from the tumor direct the recruitment of bone marrow derived cells to create a pre-metastatic niche where cancer cells can attach and develop into a metastatic lesion. Identifying and understanding these molecules can lead to the development of methods for early diagnosis or targets for intervention.
Using an orthotopic model of CRC liver metastasis, we performed microarray analyses of the liver microenvironment in tumor bearing mice before and after the arrival of metastatic cells. We found that Lipocalin-2 (LCN2, 24p3, NGAL) was highly expressed in the liver and in circulation of mice bearing highly metastatic cells. LCN2 is a 25 kD secreted glycoprotein that binds small lipophilic molecules. Its expression is upregulated in a number of primary tumors of epithelial origin, but its role in metastasis remains unclear. It has contrasting roles in metastasis in breast cancer models and has been associated with poor prognosis in CRC patients; however its role in the tumor microenvironment has not been studied. Our studies thus far show that overexpression of Lcn2 in mouse colon cancer cells either had little impact on tumor growth and invasiveness, or it enhanced invasion in the presence of macrophages; however, it resulted in an overall reduction of circulating iron levels in sera from tumor bearing mice. In-vitro, iron also seems to have an effect in conjunction with Lcn2 on the invasiveness of the tumor cells. The results from this study will allow us to better describe the role of LCN2 in tumor and stromal cells in the early stages of liver metastasis.
Citation Format: Daniel Hughes, Celestia Davis, Yu Zhang, John Bonaparte, Maria Pena. The effects of Lipocalin-2 in the early stages of colorectal cancer metastasis. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Metastasis; 2015 Nov 30-Dec 3; Austin, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(7 Suppl):Abstract nr A22.
Abstract A32: Targeting c-Met by Pterostilbene (PTER) suppresses breast cancer brain metastasis
Authors: Xing Fei , Sharma Sambad , Liu Yin , Wu Kerui , Watabe Kounosuke 
Published: May 2019

Abstract
At the late stage of breast cancer, most patients develop metastatic lesions and the brain is one of the major metastatic sites. Brain metastasis profoundly affects the cognitive and sensory function as well as morbidity of patients, and the one year survival rate among these patients remains less than 20%. The result of our newly developed gene set enrichment analysis (GSEA)-based pathway screening indicates that c-Met pathway is highly activated among the patients who developed early brain metastasis. To identify a novel target of c-Met pathway in brain metastasis, we performed the microarray analysis in two brain metastatic cell lines with the expression of doxycycline-inducible sh-cMet. Our results indicate that a group of inflammatory cytokines including IL1β, IL8 and CXCL1 were significantly induced by c-Met activation. Furthermore, we found that IL1β was able to induce the secretion of HGF (hepatocyte growth factor) from tumor associated astrocytes (TAA) which in turn activates c-Met pathway in cancer cells. Our results of endothelial cell tube formation assays also strongly suggest that c-Met-induced IL8 and CXCL1, promote tumor angiogenesis which is essential for the metastatic growth of cancer cells. Natural compounds (NC) have been extensively studied for their anti-tumor effects. However, much less studies have been done on NC for the treatment/prevention of brain tumors mainly due to the obstacle of Blood-brain-barrier (BBB) permeability. To identify the NCs that can be used for treating brain metastasis, we performed pathway analysis which only focused on BBB-permeable NC. The results of GSEA indicate that Resveratrol-targeting genes were significantly enriched among those patients who developed brain metastasis compared to metastasis-free patients. Furthermore, we found that the one of derivatives of Resveratrol, Pterostilbene (PTER), showed significantly more potent activity than Resveratrol and suppressed brain metastasis in vitro and in vivo by targeting the c-Met oncogene. These findings suggest that TAA-mediated c-Met activation plays a key role in brain metastasis and that PTER is a potential therapeutic agent to treat brain metastasis by suppressing the c-Met expression.
Citation Format: Fei Xing, Sambad Sharma, Yin Liu, Kerui Wu, Kounosuke Watabe. Targeting c-Met by Pterostilbene (PTER) suppresses breast cancer brain metastasis. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Metastasis; 2015 Nov 30-Dec 3; Austin, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(7 Suppl):Abstract nr A32.
Abstract A35: Axl overexpression in a prostate cancer mouse model delays metastasis and may prolong dormancy of disseminated tumor cells
Authors: Axelrod Haley D. , Valkenburg Kenneth C. , Pienta Kenneth J. 
Published: May 2019

Abstract
The most common site of metastasis in prostate cancer (PCa) patients is the bone marrow, where disseminated tumor cells (DTCs) preferentially home to the hematopoietic stem cell niche and can undergo a state of dormancy. These PCa cells may lie dormant in the bone marrow for years after prostatectomy, but may eventually re-enter the cell cycle resulting in lethal metastatic disease. Using mouse models of PCa metastasis, our group has previously shown that Gas6/Axl signaling is associated with dormant bone marrow DTCs. In this study we investigated the requirement of Axl in initiating and maintaining the dormant phase. We hypothesized that overexpression of Axl in PCa cells would prolong dormancy. Overexpression of Axl in the bone-homing AR-positive Axl-negative human PCa cell line C42B slows proliferation in vitro. Subcutaneous injection of C42B-Axl cells in a xenograft mouse model resulted in delayed onset of tumor growth relative to WT controls. C42B-WT tumors reached an average volume of 200mm3 at 6.6 weeks, while C42B-Axl tumors reached the same volume at 11 weeks. Regions of the primary tumor with a high percentage of Axl+ cells correlated with a low number of Ki67+ cells, indicating that Axl may inhibit proliferation even in the primary tumor. Surprisingly, C42B-Axl tumors were more vascular as observed by eye, and regions of increased vasculature correlated with a high percentage of Axl+ cancer cells. Metastatic outgrowth in soft tissues reached a lethal burden ~12 weeks following C42B-WT tumor removal, while mice bearing C42B-Axl tumors did not have detectable metastases by eye at the same timepoint post-tumor removal and were apparently healthy. Metastatic outgrowth in the bone was detected by the presence of osteoblastic and osteolytic activity at 5-12 weeks post-tumor removal in the femurs and tibiae of mice bearing C42B-WT tumors. At 8-12 weeks after C42B-Axl tumor removal, however, there was no evidence of metastatic bone disease. While these experiments are still ongoing, we have shown that Axl expression in the primary tumor delayed metastatic burden in both soft tissues and in bone in a mouse model of PCa metastasis. In ongoing studies, we will compare DTC number and time to metastasis in the bone marrow of C42B-WT and C42B-Axl tumor-bearing mice.
Citation Format: Haley D. Axelrod, Kenneth C. Valkenburg, Kenneth J. Pienta. Axl overexpression in a prostate cancer mouse model delays metastasis and may prolong dormancy of disseminated tumor cells. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Metastasis; 2015 Nov 30-Dec 3; Austin, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(7 Suppl):Abstract nr A35.