bluuebunny/crossref_metadata_2025_split huggingface dataset:
Persistent inequalities in Hospice at Home provision
Authors: Buck Jackie , Webb Liz , Moth Lorraine , Morgan Lynn , Barclay Stephen 
Published: February 2018

ObjectiveTo describe the nature and scope of a new Hospice at Home (H@H) service and to identify its equality of provision.MethodsCase note review of patients supported by a H@H service for 1 year from September 2012 to August 2013 (n=321). Descriptive analysis to report frequencies and proportions of quantitative data extracted from service logs, referral forms and care records; thematic analysis of qualitative data from care record free text.ResultsDemand outstripped supply. Twice as many night care episodes were requested (n=1237) as were provided (n=613). Inequalities in access to the service related to underlying diagnosis and socioeconomic status. 75% of patients using the service had cancer (221/293 with documented diagnosis). Of those who died at home in the areas surrounding the hospice, 53% (163/311) of people with cancer and 11% (49/431) of those without cancer received H@H support. People who received H@H care were often more affluent than the population average for the area within which they lived. Roles of the service identified included: care planning/implementation, specialist end-of-life care assessment and advice, ‘holding’ complex patients until hospice beds become available and clinical nursing care.ConclusionThere is significant unmet need and potentially large latent demand for the H@H service. People without cancer or of lower socioeconomic status are less likely to access the service. Action is needed to ensure greater and more equitable service provision in this and similar services nationally and internationally.
Developmental regulation of the intestinal FGF19 system in domestic pigs
Authors: Gavaldà-Navarro Aleix , Pastor Jose J. , Mereu Alessandro , Villarroya Francesc , Ipharraguerre Ignacio R. 
Published: February 2018

Fibroblast growth factor-19 (FGF19) is an emerging endocrine factor involved in the regulation of bile acid homeostasis and energy metabolism in rodents and humans. In pigs, however, the FGF19 system remains largely unexplored. This study was designed to investigate the developmental regulation of the FGF19 system in domestic pigs. Samples of intestinal sections, liver, and plasma were collected from 24 pigs ( n = 6) at four developmental stages (birth, preweaning, postweaning, and adulthood). In the intestine, expression of the farnesoid X receptor (FXR) and FGF19 showed a congruent time- and region-dependent regulation, beginning soon after birth to achieve maximal expression in ileum during adulthood. The same temporal pattern was followed by the circulating concentration of FGF19, and these changes were accompanied by a time-related increase in the ileal proportion of bile acids that potently activate FXR. Conversely, genes belonging to the FGF19 signaling machinery achieved maximal expression in the small intestine at birth to decrease sharply afterward. In the liver, gene expression of FGF19 receptors and enzymes involved in bile acid biosynthesis paralleled after-birth changes in plasma concentration of this enterokine and attained a maximum during postweaning when plasma FGF19 was the lowest. Although detectable at birth, the hepatic expression of genes belonging to the bile acid-FXR-FGF19 pathway was low before the onset of enteral feeding. In summary, the porcine FGF19 system is present from birth, operative before the onset of enteral feeding, and regulated in a temporal and section-specific manner. NEW & NOTEWORTHY Fibroblast growth factor-19 (FGF19) is an emerging endocrine factor. The domestic pig is a translational model of value in biomedical research. We show for the first time that in pigs the intestinal FGF19 system is present from birth, operative before the onset of enteral feeding, and regulated in a temporal and section-specific manner. This work identifies pigs as a suitable model for investigating the implications of FGF19 signaling within and beyond the gut-liver axis.
Abstract BS2-2: The perivascular niche protects dormant disseminated tumor cells from therapy
Authors: Ghajar CM 
Published: February 2018

Abstract
In a significant fraction of breast cancer patients, distant metastases emerge after years or even decades of latency. How disseminated tumor cells (DTCs) are kept dormant, and what wakes them up, are fundamental problems in tumor biology. To address these questions, we use metastasis assays in mice and zebrafish and have determined that the perivascular niche of distant sites like the lung, bone marrow and brain regulate DTC dormancy. We have developed organotypic microvascular niches to specify that endothelial cells regulate breast cancer cell growth, and applied proteomics to identify endothelial-derived mediators of DTC dormancy. More recently, we have begun to explore whether the perivascular niche confers therapeutic resistance to DTCs. I will present data that suggests strongly that the perivascular niche regulates therapeutic resistance of DTCs in a manner that is independent from its role in regulating DTC growth. We have uncovered mediators of perivascular signaling that, when targeted, cause dormant DTCs to respond robustly to chemotherapy. Critically, inhibiting these mediators causes chemosensitization without inducing dormant DTCs to re-enter the cell cycle. We are currently testing this treatment paradigm in pre-clinical models to determine the efficacy in killing dormant DTCs through this approach. I will discuss pre-clinical trial design and important caveats to accurately gauging whether eradication of dormant DTCs significantly prolongs metastasis-free survival.
Citation Format: Ghajar CM. The perivascular niche protects dormant disseminated tumor cells from therapy [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 BS2-2.
Abstract CS1-2: Searching for the optimal duration of adjuvant endocrine therapy in breast cancer
Authors: Stearns V 
Published: February 2018

Abstract
Endocrine therapy is an integral part of the adjuvant systemic management of women with early stage hormone receptor-positive breast cancer. Adjuvant endocrine therpay is associated with significant improvements in disease-free and overall survival. Several adjuvant endocrine therapy approaches are available to women based on their menopausal status, disease stage, tumor characteristics, co-morbidities, and individual preferences. The optimal duration of adjuvant endocrine therapy established to date is 5 to 10 years.
Extended adjuvant endocrine therpay provides only a modest additional benefit compared to a 5-year treatment duration. Studies reported in recent years offer some guidance to help clinicians provide recommendations regarding the type and duration of adjuvant endocrine therpay. Clinicians must weigh treatment benefits and potential adverse events for individual patients. Models to help individualize treatment recommendations are needed. Several opportunities are available to predict personalized risk of recurrence and likelihood of developing bothersome symptoms or serious adverse events. Women should have a close follow up with their physicians during the first year or therapy to identify emerging symptoms and to provide early interventions to optimize adherence to adjuvant endocrine therpay. Clinicians should engage in continuous discussion with each woman regarding the duration of treatment most appropriate for her and revisit recommendations based on evolving clinical trial results or events in the patient's life.
In this presentation I will discuss the available data regarding optimal length of adjuvant endocrine therapy. I will review expected benefits and toxicities. I will also discuss emerging biomarkers and approaches that may help individualize treatment duration for women with hormone receptor-positive breast cancer.
Citation Format: Stearns V. Searching for the optimal duration of adjuvant endocrine therapy 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 CS1-2.
Abstract ES10-2: A novel human derived organoid platform for breast cancer research
Authors: Kopper O 
Published: February 2018

Abstract
Breast cancer (BC) is a heterogeneous disease consisting of multiple tumor subtypes. We have recently established a novel human derived 3D in-vitro platform, which enables long-term expansion of BC organoids. Thus, we were able to derive ∼100 BC organoid lines from both primary and metastatic tumors. These lines represent the diversity of the disease and faithfully recapitulate the histology, hormone receptor and HER2 status of the tumors from which they were derived. Whole genome sequencing analysis of tumor-organoid pairs, demonstrated that copy number alterations and single nucleotide variations, were broadly maintained, even after extended passaging. BC organoids allowed performing in-vitro drug screens that were consistent with in-vivo xenografts and patient response.
Thus, we suggest that this platform can be utilized as a valuable tool for BC research, facilitate drug development and present us with new opportunities for personalized medicine.
Citation Format: Kopper O. A novel human derived organoid platform for breast cancer research [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 ES10-2.
Abstract ES11-1: Luminal ABC: optimal use of all available options?
Authors: DeMichele AM 
Published: February 2018

Abstract
Despite advanced in early detection and aggressive adjuvant endocrine therapy, recurrence and metastasis of estrogen-receptor (ER)- positive breast cancer remains a problem, with a substantial proportion of patients relapsing years after diagnosis. Biologically, these tumors are primarily of the luminal subtype, amenable to anti-estrogen strategies that can control disease growth and limit metastatic spread. However, resistance and progression are universal, and patients will eventually stop responding to endocrine approaches. Advances in our understanding of luminal breast cancer biology, metastatic progression and endocrine resistance have led to new approaches and additional targets for intervention. Most important among these are interactions between ER signaling pathways and cell cycle control mechanisms or PI3K/mTor signaling, leading to new strategies incorporating cyclin-dependent kinase (cdk) and mTOR inhibitors, respectively, into endocrine therapy. While successful, many questions remain unanswered regarding optimal combinations and sequencing of these agents in specific populations, and management at the time of progression. This session will address (1) the evidence supporting the use of cdk 4/6 and mTOR inhibitors in standard practice for luminal advanced breast cancer, including agent selection and management of toxicity, (2) current understanding of resistance mechanisms and (3) next generation clinical trials designed to address resistance and improve outcomes in women with luminal advanced breast cancer.
Citation Format: DeMichele AM. Luminal ABC: optimal use of all available options? [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 ES11-1.
Abstract ES5-3: Biologic and health system determinants of breast cancer disparities in African Americans
Authors: Reeder-Hayes KE 
Published: February 2018

Abstract
Despite significant progress in breast cancer screening and treatment over three decades, racial disparities in breast cancer mortality between African American (AA) and White women continue to widen. A cascade of factors, both biological and ecological, drive these disparities, including: (1) differences in presenting stage and uptake of breast cancer screening; (2) differences in subtype distribution, beginning with over-representation of hormone receptor negative, HER2 negative (triple negative) tumors in young AA women, and extending to recent evidence of potential biologic differences within hormone receptor positive (HR+) subtypes; (3) barriers to appropriate delivery of breast cancer care for AA women, including chemotherapy, radiation and targeted endocrine and biologic therapies; (4) differences in the impact of cancer treatment during survivorship and the impact of co-morbidities on post-diagnosis risk, including obesity, health-related quality of life and financial toxicity. Although the biologic and health system contributors to breast cancer disparities in AA women have been well studied, interventions designed to improve health equity for AA women with breast cancer are only beginning to emerge. Meaningful improvement in the survival gap will require close examination of how biology and healthcare access act as drivers of sub-optimal outcomes, and how both can be targeted to improve outcomes. Interventions with promise to impact racial disparities include programs that improve access to screening, patient navigation programs, and interventions to improve adherence to endocrine therapy, and some of these approaches are being tested in ongoing clinical trials. The impact of access to insurance should also be considered as an intervention for vulnerable populations, including AA women. Basic and translational research including efforts to identify therapeutic targets in triple negative breast cancer subtypes and to leverage genomics for better identification of high risk HR+ cancers may also disproportionately benefit AA patients due to their over-representation in these subtypes, but these efforts depend on adequate representation of AA patients in tissue biobanks and clinical trials, as well as adequate access to genomic testing.
Citation Format: Reeder-Hayes KE. Biologic and health system determinants of breast cancer disparities in African Americans [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 ES5-3.
Abstract ES6-3: Opportunities for immune therapy and prevention
Authors: Vonderheide RH 
Published: February 2018

Abstract
The recent demonstration of modest single-agent activity of PD-L1 and PD-1 antibodies in patients with breast cancer has generated hope for advancing immunotherapy in this disease. Depending on the subtype of breast cancer, in both primary and metastatic disease, the extent of tumor-infiltrating T cells is not only prognostic for survival but predictive of response to non-immune, standard therapies. Despite these findings, immune cytolytic activity in spontaneous breast tumors, the burden of nonsynonymous tumor mutations, and the predicted load of neo-epitopes – factors linked to response to checkpoint blockade in other malignancies – are all relatively modest in breast cancer, compared to melanoma or lung cancer. Thus, in breast cancer, combinations of immune agents with non-redundant mechanisms of action are the high-priority strategies. For most breast cancers that exhibit relatively modest T cell infiltration, major challenges include immune suppression in the tumor microenvironment as well as failed or suboptimal T cell priming. Agents that trigger de novo T cell responses may be critical for successful development of cancer immunotherapy and immune prevention in breast cancer. Success may also require reaching beyond nonsynonymous mutations as the T cell epitopes to target, especially as numerous unmutated proteins were validated as breast cancer associated antigens in the pre-checkpoint era. A deeper understanding of the immunobiology of breast cancer will be critical for immunotherapy to become broadly relevant in this disease.
Citation Format: Vonderheide RH. Opportunities for immune therapy and prevention [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 ES6-3.
Abstract ES7-1: Challenges in the management of locoregional recurrence
Authors: Morrow M 
Published: February 2018

Abstract
The increasing trend toward tailoring treatment of the primary breast cancer with limited surgery of both the breast and axilla has increased the challenge of managing locoregional recurrence (LRR). In the era when patients uniformly had axillary dissection, the appropriateness of repeat sentinel node biopsy was not a question. Similarly, the dogma that all ipsilateral breast tumor recurrences must be treated with mastectomy if the breast has been previously irradiated is also being challenged. LRR events are infrequent with modern multi-modality therapy, and there are no randomized trials to address these questions.
Re-operative sentinel node (SN) biopsy after breast conserving surgery therapy (BCT) has been shown to be feasible, with the likelihood of identifying additional SNs related to the number of nodes excised at the time of initial SN biopsy. The accuracy of SN biopsy after mastectomy is less clear. However, the impact of identification of nodal disease on management of LRR is controversial. In a study of 12 patients with isolated chest wall recurrence post mastectomy, 10/12 had successful mapping and 7/10 had an axillary SN. The absence of nodal metastases was an indication to avoid supraclavicular RT (Johnson J. Ann Surg Oncol 2016;23:715). In a study of 83 patients with in breast (n=79) or chest wall recurrence who were clinically node negative, 47 had axillary surgery and 36 did not. At a median of 4.2 years after LR, rates of axillary and non-axillary local recurrence, distant metastases, and death did not differ significantly between groups (Ugras S. Ann Surg Oncol 2016). With the findings of the CALOR trial that systemic chemotherapy is beneficial in the management of LRR, the finding of axillary metastases is less likely to influence systemic therapy than in the past and repeat axillary staging could potentially be avoided.
In the untreated breast, drainage to the contralateral axilla is very rare and contralateral axillary metastases classify a patient as Stage IV. After initial axillary dissection, between 4% and 33% of patients with local recurrence will have contralateral axillary drainage. In a systemic review of 48 cases of contralateral nodal recurrence without other distant metastatic disease, at a mean follow-up of 50.3 months disease free survival was 65% and overall survival 83% after treatment that included both local and systemic therapy (Moossdorff M. Eur J Surg Oncol 2015;41:1128). These findings raise the possibility that in the setting of LR, contralateral axillary metastases should be treated aggressively for cure after excluding distant metastases.
Citation Format: Morrow M. Challenges in the management of locoregional recurrence [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 ES7-1.
Abstract ES7-2: Local regional recurrence
Authors: Zellars RC 
Published: February 2018

Abstract
Through careful study, we are certain of the management necessary to achieve excellent local regional control rates in early stage breast cancer (ESBC). Due to less study, there is some uncertainty on how to best manage the small percentage of women with ESBC who have local regional recurrences (LRR). Classically, the management of LRR requires some form of salvage surgery. The surgery could be limited, as in wide local excision after initial mastectomy, or more radical, as in mastectomy after initial breast conserving therapy. Often after salvage surgery, radiation, or in some cases re-irradiation, is added. Today there is information which calls into question whether these common treatments for LRR are required, sufficient or the sole options. During this session, we will review the data supporting these common treatments for LRR, as well as alternatives such as surgery alone, partial breast re-irradiation, photodynamic therapy and hyperthermia. After the presentation, the attendee will have a greater understanding of the various local therapy options for treating LRR of breast cancer and the need for prospective study of this small but significant group of patients.
Citation Format: Zellars RC. Local regional recurrence [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 ES7-2.
Abstract ES8-2: Exosome analysis in breast cancer: Clinical translation
Authors: Bromberg JF 
Published: February 2018

Abstract
There is a growing appreciation that tumor secreted factors can function by orchestrating the cross-talk between cancer, stromal and immune cells. Tumors constitutively release membrane-derived extracellular vesicles (EVs) or exosomes that are readily detected in body fluids and have been appreciated to play important roles in signaling, immunomodulation and metastasis. We examined the role of circulating and stromal-derived EVs in hormonal therapy resistant breast cancer. We identified the full mitochondrial genome in circulating extracellular vesicles (EVs) from patients with hormonal-therapy resistant metastatic breast cancer. We generated xenograft models of hormonal therapy-resistant (HTR) metastatic disease characterized by EVs in the peripheral circulation containing mtDNA. Moreover, these human HT-resistant cells had acquired host-derived (murine) mtDNA promoting ER-independent metabolic proficiency. Functional studies identified cancer associated fibroblasts (CAF)-derived EVs (from patients and xenograft models) laden with the complete mitochondrial genome as a mediator of this phenotype. Specifically, the treatment of HT-naïve cells or HT-treated metabolically dormant populations with CAF-derived mtDNAhi EVs promoted an escape from metabolic quiescence and HTR disease both in vitro and in vivo. Moreover, this phenotype was associated with the acquisition of EV-mtDNA especially in cancer stem-like cells, expression of EV-mtRNA and restoration of metabolic activity. In addition to mtDNA, we also identified miR-221 in CAF derived EVs as a driver of HTR disease. Specifically, EV-mediated transfer of miR-221 to cancer cells and, in combination with hormone therapy, activated an ERlo/Notchhi feed-forward loop responsible for the generation of CD133hi cancer stem like cells. We further determined that the IL6-pStat3 pathway promoted the biogenesis of onco-miR-221hi CAF EVs. Our results illuminate how EV-mediated horizontal transfer of genetic material from host stromal cells to cancer cells triggers the evolution of therapy-resistant metastases, with potentially broad implications for their control.
Citation Format: Bromberg JF. Exosome analysis in breast cancer: Clinical translation [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 ES8-2.