bluuebunny/crossref_metadata_2025 huggingface dataset:
Protocol for a scoping review of implementation research approaches to universal health coverage in Africa
Authors: Nnaji Chukwudi A , Wiysonge Charles S , Okeibunor Joseph , Malinga Thobile , Adamu Abdu A , Tumusiime Prosper , Karamagi Humphrey
Published: February 2021

Introduction

Implementation research has emerged as part of evidence-based decision-making efforts to plug current gaps in the translation of research evidence into health policy and practice. While there has been a growing number of institutions and initiatives promoting the uptake of implementation research in Africa, their role and effectiveness remain unclear, particularly in the context of universal health coverage (UHC). This review aims to extensively identify and characterise the nature, facilitators and barriers to the use of implementation research for assessing or evaluating UHC-related interventions or programmes in Africa.

Methods and analysis

This scoping review will be developed based on the methodological framework proposed by Arksey and O’Malley and enhanced by the Joanna Briggs Institute. It will be reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines. A comprehensive search of the following electronic databases will be conducted: Medline (via PubMed), Scopus and the Cochrane Library. Relevant grey literature and reference lists will also be searched. All publications describing the application of implementation research in the context of UHC will be considered for inclusion. Findings will be narratively synthesised and analysed using a predefined conceptual framework. Where applicable, quantitative evidence will be aggregated using summary statistics. There will be consultation of stakeholders, including UHC-oriented health professionals, programme managers, implementation researchers and policy-makers; to provide methodological, conceptual and practical insights.

Ethics and dissemination

The data used in this review will be sourced from publicly available literature; hence, this study will not require ethical approval. Findings and recommendations will be disseminated to reach a diverse audience, including UHC advocates, implementation researchers and key health system stakeholders within the African region. Additionally, findings will be disseminated through an open-access publication in a relevant peer-reviewed journal.
Instruments for measuring nursing research competence: a protocol for a scoping review
Authors: Chen Qirong , Huang Chongmei , Castro Aimee R , Tang Siyuan
Published: February 2021

Introduction

Nursing research competence of nursing personnel has received much attention in recent years, as nursing has developed as both an independent academic discipline and an evidence-based practiing profession. Instruments for appraising nursing research competence are important, as they can be used to assess nursing research competence of the target population, showing changes of this variable over time and measuring the effectiveness of interventions for improving nursing research competence. There is a need to map the current state of the science of the instruments for nursing research competence, and to identify well validated and reliable instruments. This paper describes a protocol for a scoping review to identify, evaluate, compare and summarise the instruments designed to measure nursing research competence.

Methods and analysis

The scoping review will be conducted following Arksey and O’Malley’s methodological framework and Levacet al’s additional recommendations for applying this framework. The scoping review will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews checklist. The protocol is registered through the Open Science Framework (https://osf.io/ksh43/). Eight English databases and two Chinese databases will be searched between 1 December 2020 and 31 December 2020 to retrieve manuscripts which include instrument(s) of nursing research competence. The literature screening and data extraction will be conducted by two researchers, independently. A third researcher will be involved when consensus is needed. The COnsensus-based Standards for the selection of health Measurement INstruments methodology will be used to evaluate the methodological quality of the included studies on measurement properties of the instruments, as well as the quality of all the instruments identified.

Ethics and dissemination

Ethical approval is not needed. We will disseminate the findings through a conference focusing on nursing research competence and publication of the results in a peer-reviewed journal.
Improving centre-based group exercise participation of older adults using the behaviour change wheel
Authors: Kwok Boon Chong , Wong Wai Pong , Remedios Louisa
Published: February 2021

An emphasis on active ageing could help to delay the onset of frailty. In Singapore, Senior Activity Centres provide free and guided group exercise sessions for older adults. However, one such centre had very low participation rates among community-dwelling older adults despite running standardised programmes. Based on a needs analysis from a prior project, this paper reports on strategies implemented to improve the daily centre-based group exercise participation rate among community-dwelling older adults. Using the behaviour change wheel model, participant motivation domains were identified as primary gaps, while the psychological capability and physical opportunity were categorised as secondary gaps. A logic model was used to design a project to respond to these identified gaps and guide the evaluation approach. Three strategies were implemented over a 4-week period and reviewed at 6 months: (1) promotion of the exercise classes, (2) delayed rewards for participation and (3) health ambassadors. Evaluation findings highlighted that more resources were needed for the training of community-dwelling older adult healthcare ambassadors in the use of motivational interviewing. The interventions were found to be efficacious in increasing daily group exercise participation rate at the centre, from an average of three to nine participants per day over the 4 weeks. Furthermore, more than 60% of these participants achieved the WHO’s weekly minimum exercise recommendation for older adults (150 min moderate-intensity physical activity). To increase the engagement of older adults in physical activity or exercise participation, we recommend the use of behaviour change wheel model and the use of community-based health ambassadors. In conclusion, the project found improved daily centre-based group physical exercise participation rates when all the domains in the behaviour change wheel model were addressed.
WHSC1/NSD2 regulates immune infiltration in prostate cancer
Authors: Want Muzamil Y , Tsuji Takemasa , Singh Prashant K , Thorne James L , Matsuzaki Junko , Karasik Ellen , Gillard Bryan , Cortes Gomez Eduardo , Koya Richard C. , Lugade Amit , Odunsi Kunle , Battaglia Sebastiano
Published: February 2021

Background

Immunotherapy in prostate cancer (PCa) lags behind the progresses obtained in other cancer types partially because of its limited immune infiltration. Tumor-resident immune cells have been detected in the prostate, but the regulatory mechanisms that govern tumor infiltration are still poorly understood. To address this gap, we investigated the role of Wolf-Hirschhorn syndrome candidate 1 (WHSC1), a histone methyltransferase enzyme that targets dimethyl and trimethyl H3K36. WHSC1 is known to promote malignant growth and progression in multiple tumors, but its role in the interface between PCa and immune system is unknown.

Methods

RNA Sequencing (RNASeq) data from patients with PCa from The Cancer Genome Atlas (TCGA) were collected and divided into top/bottom 30% based on the expression of WHSC1 and disease-free survival was calculated. Publicly available chromatin immunoprecipitation (ChIPSeq) data were obtained from Cistrome and integrated with the available RNASeq data. RNASeq, ATACSeq and methylomic were analyzed using R Bioconductor packages comparing C42 cells with or without stable knockdown on WHSC1. Flow cytometry was used to measure Major Histocompatibility complex (MHC) levels, MHC-bound ovalbumin and tumor infiltration. C57B6 and NOD scid gamma (NSG) mice were subcutaneously grafted with TRansgenic Adenocarcinoma of the Mouse Prostate (TRAMP) C2 cells and treated with MCTP39 (10 mg/kg); tumor size was monitored over time and curves were compared using permutation analyses. All analyses used a significance threshold of 0.05.

Results

Leveraging TCGA data, we demonstrated that elevated WHSC1 levels positively correlate with the presence of an immunosuppressive microenvironment. We validated those results in vitro, demonstrating that genetic and pharmacological inhibition of WHSC1 restores antigen presentation. This occurs via an elegant epigenetic regulation of gene expression at the chromatin and DNA methylation levels. In vivo studies in immunocompetent mice also show an increased frequency of CD8+ T cells in tumors from mice treated with WHSC1 inhibitor, supporting the hypothesis that the antitumor effect following WHSC1 inhibition requires a fully functional immune system.

Conclusions

This study demonstrates a novel role for WHSC1 in defining immune infiltration in PCa, with significant future implications for the use of immunotherapies in prostate malignancies.
Immune-mediated ototoxicity associated with immune checkpoint inhibitors in patients with melanoma
Authors: Rosner Samuel , Agrawal Yuri , Sun Daniel Q , Aygun Nafi , Schollenberger Megan D , Lipson Evan , Naidoo Jarushka
Published: February 2021

Immune checkpoint inhibitors (ICIs) are associated with a range of organ-specific toxicities known as immune-related adverse events (irAEs). Immune-mediated ototoxicity from ICIs is poorly described. Herein, we describe the clinical presentation, diagnostic evaluation and management of six ICI-treated patients who developed immune-mediated ototoxicity, identified by a multidisciplinary immune-related toxicity team. This is the largest case series to date and identifies bilateral high-frequency hearing loss and tinnitus as the most common reported symptoms and can be associated with abnormal speech reception thresholds and word recognition ability on audiogram in select patients. We propose multidisciplinary evaluation of patients with suspected otologic irAEs including referral to otolaryngology, audiometry evaluation±magnetic resonance imaging for evaluation of suspected immune-mediated ototoxicity.
Integrating genome-wide CRISPR immune screen with multi-omic clinical data reveals distinct classes of tumor intrinsic immune regulators
Authors: Hou Jiakai , Wang Yunfei , Shi Leilei , Chen Yuan , Xu Chunyu , Saeedi Arash , Pan Ke , Bohat Ritu , Egan Nicholas A. , McKenzie Jodi A. , Mbofung Rina M. , Williams Leila J. , Yang Zhenhuang , Sun Ming , Liang Xiaofang , Rodon Ahnert Jordi , Varadarajan Navin , Yee Cassian , Chen Yiwen , Hwu Patrick , Peng Weiyi
Published: February 2021

Background

Despite approval of immunotherapy for a wide range of cancers, the majority of patients fail to respond to immunotherapy or relapse following initial response. These failures may be attributed to immunosuppressive mechanisms co-opted by tumor cells. However, it is challenging to use conventional methods to systematically evaluate the potential of tumor intrinsic factors to act as immune regulators in patients with cancer.

Methods

To identify immunosuppressive mechanisms in non-responders to cancer immunotherapy in an unbiased manner, we performed genome-wide CRISPR immune screens and integrated our results with multi-omics clinical data to evaluate the role of tumor intrinsic factors in regulating two rate-limiting steps of cancer immunotherapy, namely, T cell tumor infiltration and T cell-mediated tumor killing.

Results

Our studies revealed two distinct types of immune resistance regulators and demonstrated their potential as therapeutic targets to improve the efficacy of immunotherapy. Among them, PRMT1 and RIPK1 were identified as a dual immune resistance regulator and a cytotoxicity resistance regulator, respectively. Although the magnitude varied between different types of immunotherapy, genetically targetingPRMT1andRIPK1sensitized tumors to T-cell killing and anti-PD-1/OX40 treatment. Interestingly, a RIPK1-specific inhibitor enhanced the antitumor activity of T cell-based and anti-OX40 therapy, despite limited impact on T cell tumor infiltration.

Conclusions

Collectively, the data provide a rich resource of novel targets for rational immuno-oncology combinations.
Regional and local effects drive changes in spawning stream occupancy in a sockeye salmon metapopulation
Authors: Bradford Michael J. , Braun Douglas C.
Published: February 2021

There is a need to explicitly consider metapopulation dynamics in the development of conservation strategies for spatially structured populations. We examined the spatial dynamics of sockeye salmon (Oncorhynchus nerka) that spawn in 36 streams of the Stuart River watershed in British Columbia, Canada, using a 69-year record of spawner abundance and a demographically based Bayesian dynamic occupancy model. We identified a set of 12 streams with good habitat conditions that were occupied >90% of years despite large year-to-year changes in abundance. Over 85% of spawners were concentrated in these streams. Many other streams with poorer habitat had small populations that were not persistent over time and were periodically recolonized by dispersers from other streams. Although it is often assumed population diversity and resiliency is maximized when all available habitats are used, for this salmon metapopulation, resiliency is due to the core streams of higher habitat quality. Currently, other streams make only small contributions to population abundance; however, some may have conservation value if their habitats become more suitable for spawning in the future.
1,25-Dihydroxyvitamin D deficiency accelerates male reproductive senescence in aging mice and 1,25(OH)2D3alleviates oxidative stress via NF-κB/SOD
Authors: He Jialing , Wang Hui , Shi Jiaxin , Shi Mengfan , Sun Weiwei
Published: February 2021

Based on this studies, we propose that 1,25(OH)2D3can delay male reproductive aging, and we also propose that 1,25(OH)2D3regulates NF-κB to exert antioxidant effect. Therefore, by targeting a fundamental aging mechanism, 1,25(OH)2D3may be an effective agent in maintaining fertility and postponing male reproductive senescence.
Increased SGK1 activity potentiates mineralocorticoid/NaCl-induced kidney injury
Authors: Sierra-Ramos Catalina , Velazquez-Garcia Silvia , Keskus Ayse G. , Vastola-Mascolo Arianna , Rodríguez-Rodríguez Ana E. , Luis-Lima Sergio , Hernández Guadalberto , Navarro-González Juan F. , Porrini Esteban , Konu Ozlen , Alvarez de la Rosa Diego
Published: February 2021

Increased activity of protein kinase SGK1 may be a risk factor for accelerated renal damage. SGK1 expression could be a marker for rapid progression toward CKD and a potential therapeutic target to slow down the process.
Defining Heritage Science: A Consilience Pathway to Treasuring the Complexity of Inheritable Human Experiences through Historical Method, AI, and ML
Authors: Nanetti Andrea
Published: February 2021

Societies have always used their heritage to remain resilient and to express their cultural identities. Today, all the still‐available experiences accrued by human societies over time and across space are, in principle, essential in coping with the twenty‐first century grand challenges of humanity (refer to the 17 UN Sustainable Development Goals). Artificial intelligence and machine learning algorithms can assist the next generation of historians, heritage stakeholders, and decision‐makers in (1) decoding unstructured knowledge and wisdom embedded in selected cultural artefacts and social rituals, (2) encoding data in machine‐readable systems, (3) aggregating information according to the user’s needs in real time, and (4) simulating the consequences of either erasing, neglecting, putting in latency, or preserving and sharing specific human experiences. What our global society needs is a multilingual and transcultural approach to decode‐encode the treasure of human experience and transmit it to the next generation of world citizens. This approach can be the pathway to work on a new science of heritage, its ethics, and empathy.
Detecting Pronunciation Errors in Spoken English Tests Based on Multifeature Fusion Algorithm
Authors: Wang Yinping
Published: February 2021

In this study, multidimensional feature extraction is performed on the U‐language recordings of the test takers, and these features are evaluated separately, with five categories of features: pronunciation, fluency, vocabulary, grammar, and semantics. A deep neural network model is constructed to model the feature values to obtain the final score. Based on the previous research, this study uses a deep neural network training model instead of linear regression to improve the correlation between model score and expert score. The method of using word frequency for semantic scoring is replaced by the LDA topic model for semantic analysis, which eliminates the need for experts to manually label keywords before scoring and truly automates the critique. Also, this paper introduces text cleaning after speech recognition and deep learning‐based speech noise reduction technology in the scoring model, which improves the accuracy of speech recognition and the overall accuracy of the scoring model. Also, innovative applications and improvements are made to key technologies, and the latest technical solutions are integrated and improved. A new open oral grading model is proposed and implemented, and innovations are made in the method of speech feature extraction to improve the dimensionality of open oral grading.
Abstract PD1-08: Oral paclitaxel and encequidar (oPac+E) versus IV paclitaxel (IVPac) in the treatment of metastatic breast cancer (mBC) patients (study KX-ORAX-001): Progression free survival (PFS) and overall survival (OS) updates
Authors: Umanzor G , Rugo H S , Barrios F J , Vasallo R H , Chivalan M A , Bejarano S , Ramirez J R , Fein L , Kowalyszyn R D , Cutler D L , Kramer D , Goldfinch J , Wang H , Moore T , Kwan R MF
Published: February 2021

Background: IVPac is widely used to treat patients with breast cancer. oPac+E is oral paclitaxel in combination with Encequidar, an oral, minimally absorbed, specific p-glycoprotein inhibitor that enables the absorption of oral paclitaxel. Results of the phase III trial, KX-ORAX-001, were presented at SABCS, 2019, Abstract # GS6-01. At the time of the database lock for the final analysis of the primary endpoint of confirmed tumor response rate, analyses of PFS and OS were performed. The confirmed tumor response rate was significantly higher in the oPac+E group vs IVPac (35.8% vs 23.4%, p=0.011 ITT, population). The median overall survival was 27.7 months vs 16.7 months, respectively favoring oPac. An update of the duration of response, PFS and OS data comprising an additional 14 months follow-up will be presented. At the time of the update it is projected that approximately 60% of subjects will have had a survival event.

Methods: Study KX-ORAX-001 was a phase III, randomized, international study in women with mBC for whom treatment with IVPac was recommended. Eligible patients were randomized 2:1 to receive oPac+E or IVPac. Patients continued treatment until discontinuation due to progressive disease or toxicity. oPac 205 mg/m2 was given once daily for 3 days weekly. E 12.9 mg was given 1 hour before each dose of oPac. IVPac 175 mg/m2 was infused over 3 hours every 3 weeks. The primary endpoint was efficacy defined as tumor response confirmed by BICR at two consecutive evaluations. Key secondary endpoints included PFS, OS. Safety was monitored throughout the study.

Results: A total of 402 mBC patients were randomized (oPac+E 265: IVPac 137) and represent the ITT population of which 399 subjects were dosed. Updated data for duration of response, PFS and OS for the ITT and prespecified mITT populations will be presented. (NCT 02594371)

Citation Format: G Umanzor, H S Rugo, F J Barrios, R H Vasallo, M A Chivalan, S Bejarano, J R Ramirez, L Fein, R D Kowalyszyn, D L Cutler, D Kramer, J Goldfinch, H Wang, T Moore, R MF Kwan. Oral paclitaxel and encequidar (oPac+E) versus IV paclitaxel (IVPac) in the treatment of metastatic breast cancer (mBC) patients (study KX-ORAX-001): Progression free survival (PFS) and overall survival (OS) updates [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD1-08.
Abstract PD12-07: Incidences of endometrial events and frequencies of endometrial invasive diagnostic procedures in breast cancer survivors on tamoxifen: A nationwide study
Authors: Choi Soojeong , Jeong Jae ho , Jung Jinhong , Lee Young Jae , Lee Jong Won , Ko Beom Seok , Son Byung Ho , Ahn Sei Hyun , Lee Yura , Kim Hee jeong , Chung Il Yong
Published: February 2021

BackgroundBreast cancer survivors who taking tamoxifen as adjuvant therapy have been reported to have more endometrial lesions. According to guidelines, a gynecological assessment is recommended for postmenopausal women, but there is no mention of premenopausal women. The purpose of this study is to compare the risk of endometrial cancer by age at diagnosis, and to investigate frequencies of gynecological exam in breast cancer patients taking tamoxifen in South Korea.

MethodsA nationwide retrospective cohort study was conducted using South Korea Health Insurance Review and Assessment Service claims data. Between 2010 and 2015, a total of 60,545 (mean follow-up, 66.0 months) newly diagnosed female breast cancer survivors were included. Endometrial evaluation and Dilatation & Curettage (D&C) proportion were analyzed by age at diagnosis. The incidence of endometrial cancer and benign lesions were calculated as incident cases per person-year and analyzed with the Kaplan-Meier method. ResultsThe 26,374 patients who taking tamoxifen were divided into four groups by age at diagnosis. The incidence rate of endometrial cancer per 1,000 person-years was 1.13 and 1.45 for age range 50-59 and over 60 and 0.62 and 0.82 for in age under 40 and range 40-49. However, D&C proportion did not all differ from 10 to 11% in each subgroup.

ConclusionsThis nationwide cohort study showed that the risk of endometrial cancer in premenopausal breast cancer women taking tamoxifen was lower than that of postmenopausal women. However, the invasive diagnostic procedure such as aspiration, biopsy, polypectomy and D&C was proceeding at a level that makes no difference with those in postmenopausal women.

Citation Format: Soojeong Choi, Jae ho Jeong, Jinhong Jung, Young Jae Lee, Jong Won Lee, Beom Seok Ko, Byung Ho Son, Sei Hyun Ahn, Yura Lee, Hee jeong Kim, Il Yong Chung. Incidences of endometrial events and frequencies of endometrial invasive diagnostic procedures in breast cancer survivors on tamoxifen: A nationwide study [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD12-07.
Abstract PD15-08: The role of purinergic signaling in the chemotherapy response of triple negative breast cancer
Authors: Manouchehri Jasmine , Datta Jharna , Cherian Mathew
Published: February 2021

Triple negative breast cancer (TNBC) affects women worldwide with a higher incidence in minority populations. Patients with TNBCs often have poorer prognoses in comparison to other breast cancer sub-types due to a lack of effective therapeutic options. Chemotherapy and immunotherapy are the only effective treatments, but these modalities generally result in short-term response. Therefore, there is a need to identify additional therapies to intensify the chemotherapeutic response in TNBC. When cancer cells are exposed to chemotherapy, they release adenosine triphosphate (ATP) into the extracellular space. Extracellular ATP is degraded by CD39 (E-NTPDase) to adenosine diphosphate (ADP) and then adenosine monophosphate (AMP), and AMP is broken down to adenosine by CD73. We examined the potential role of extracellular ATP in chemotherapy- induced cancer cell death. We hypothesized that extracellular ATP sensitizes TNBC cells to chemotherapy and that ATP degrading enzymes such as CD39 and CD73 attenuate this effect. TNBC MDA-MB 231, MDA-MB 468, and Hs 578t cell lines were treated with the chemotherapeutic agent paclitaxel for different time courses. Extracellular ATP was measured via the ATPlite 1step luminescence assay, and cell viability was assessed by applying PrestoBlue HS cell viability reagent. Paclitaxel-treated TNBC cell lines revealed a dose-dependent increase in extracellular ATP release in the presence of an inhibitor of CD39 (POM-1), accompanied by a dose-dependent decrease in cell viability. In addition, the general P2X receptor (P2RX) inhibitor iso-PPADS and the P2RX7 specific inhibitor (A438079) were added separately to observe if the P2X receptors are necessary for the release of ATP upon paclitaxel treatment. After paclitaxel treatment, TNBC cell lines showed a decline in the amount of ATP released with the addition of the inhibitors iso-PPADS and A438079. Treatment of non-tumorigenic immortalized MCF-10A mammary epithelial cells with paclitaxel in the presence and absence of the inhibitors iso-PPADS and A438079 did not result in a significant increase in extracellular ATP or a decrease in cell viability. These results indicate that P2RX7 is necessary for ATP release in TNBC cell lines exposed to chemotherapy. Furthermore, when TNBC cell lines were treated with increasing concentrations of ATP, there was a dose-dependent decrease in cell viability. Overall, these findings suggest that extracellular ATP may impact the chemotherapeutic response in TNBC cell lines through the activation of the ATP-gated channel P2RX7.

Citation Format: Jasmine Manouchehri, Jharna Datta, Mathew Cherian. The role of purinergic signaling in the chemotherapy response of triple negative breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD15-08.
Abstract PD5-07: Mapping the tumor and microenvironmental evolution underlying DCIS progression throughmultiplexed ion beam imaging
Authors: Angelo Michael
Published: February 2021

Ductal Carcinoma in Situ (DCIS) is a pre-invasive lesion that accounts for nearly 20% of new breast cancer diagnoses. Of these cases, about half will progress to invasive breast cancer (IBC) within ten years. However, because diagnostic criteria for delineating low risk lesions from those likely to progress to IBC have not been identified, many patients are receiving unnecessary chemotherapy and surgery that can result in therapy-related morbidity and death. With this in mind, we used Multiplexed Ion Beam Imaging by time of flight (MIBI-TOF) and RNA-seq laser-capture microdissection (SMART-3SEQ) to construct a comprehensive spatial atlas describing the structure, function, and cellular composition of DCIS. MIBI-TOF and SMART-3SEQ were used to compare lesions from patients that later developed IBC with those from age- and history matched DCIS controls without recurrence. Using a 37-marker staining panel to interrogate 137 lesions, we identified 17 distinct cell populations of epithelial, stromal, and immune cells that were arranged in recurrent cellular microenvironments specific for DCIS or invasive disease. We observe a coordinated shift in the immune and stromal compartments as invasive disease arises, including a robust influx of lymphocytes and expansion reactive stromal phenotypes in synchronous DCIS + IBC, which was distinct from the macrophage-dominant, highly vascularized microenvironment of recurrent IBC. Further, single cell segmentation using a deep learning model was combined with pixel-level coexpression analysis to extensively evaluate how the thickness, continuity, and phenotype of ductal myoepithelium changes as tumors progress from a pre-invasive state. These data were incorporated into a comprehensive model which was subsequently used to identify a subset of features that correlate with disease-free survival following DCIS tumor resection. Taken together, these features represent important prognostic metrics that can be used to separate pre-invasive from indolent DCIS tumors, and allow for tailored therapy that improves patient outcomes and quality of life in this disease.

Citation Format: Michael Angelo. Mapping the tumor and microenvironmental evolution underlying DCIS progression throughmultiplexed ion beam imaging [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD5-07.
Abstract PD9-12: Concordance and use patterns of tissue and cell-free based genomic testing in metastatic breast cancer
Authors: Liu Minetta , Schaffer Jeff , Piwowarczyk Aneta , Beaubier Nike , Blackwell Kimberly , Park Ben
Published: February 2021

Genomic testing has transformed clinical care in metastatic breast cancer. Cell-free DNA (cfDNA) has made sequential testing feasible, however, concordance between tissue and cfDNA, sensitivity of cfDNA, and optimal sampling frequency have not been examined on large data sets with clinical annotation. Of the 648 genes in the tissue NGS Tempus xT assay, 105 genes are also included in the Tempus xF cfDNA plasma-based test. Both platforms are run on Illumina and detect SNVs, indels, CNVs, and rearrangements/fusions with high sensitivity and specificity (>90%). This study used the Tempus Labs LENS™ tool to identify the most recent ~3,300 metastatic breast cancer patients who underwent clinical testing and had either tissue-based testing, cfDNA testing or both. Of the 212 patients with xF and xT testing, 87 had xT before xF, 135 had xF before xT, and 7 had the testing performed at the same time. The most common pathogenic germline versus somatic alterations on tissue-based testing and their concordance will also be reported. In summary, this data suggests a variable amount of concordance between tissue-based and plasma-based assays. Timing of assay performance and inclusion of germline DNA might play an important role in contributing to these differences which need further exploration.

Table: Count of Reported Variants and xT/xF Concordance by GeneSomatic GenesxF frequency (n)xT frequency(n)Concordance Between xF and xTTP5313911043%PIK3CA848058%ESR1584141%BRCA238217%ERBB2372629%NF1322113%RB1272416%ATM30165%GATA3213441%FGFR13353%PTEN193036%ARID1A251823%

Citation Format: Minetta Liu, Jeff Schaffer, Aneta Piwowarczyk, Nike Beaubier, Kimberly Blackwell, Ben Park. Concordance and use patterns of tissue and cell-free based genomic testing in metastatic breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD9-12.
Abstract PS1-20: Pathologic lymph lode status of patients with T1 HER2-positive breast cancer who did not receive neoadjuvant chemotherapy using the national cancer database
Authors: DeCesare Laura , Perez Claudia , Nimmagadda Neha , Zhang Yanyu , Terranella Samantha , Skertich Nicholas , Wiegmann Aaron , Madrigrano Andrea , Alvarado Rosalinda , O'Donoghue Cristina
Published: February 2021

Purpose: HER2 directed neoadjuvant therapies for locally advanced HER2-positive breast cancer have improved complete pathologic response and event-free survival. For T1 breast cancer, lymph node status often determines whether neoadjuvant treatment is indicated. The aim of this study was to identify patient and tumor characteristics using the National Cancer Database.Methods: A retrospective review of patents diagnosed with T1 clinically node negative (cT1N0) HER2-positive breast cancers was performed using the American College of Surgeons National Cancer Database (ACS NCDB) from 2004-2016. Exclusion criteria included age <18 years and neoadjuvant treatment. Primary outcome was lymph node status. Additional variables included: age, tumor size, tumor location, histology, grade, lymphovascular invasion (LVI), grade, and estrogen receptor (ER) and progesterone receptor (PR) status. Chi-Square tests were performed to evaluate the relationship between these variables and lymph node positive disease.

Results: A total of 57,366 T1 HER2-positive patients were identified with 8,994 patients (15.68%) having positive lymph nodes. Characteristics associated with lymph node involvement included age (p<0.001), tumor location (p<0.001), lymphovascular involvement (p<0.001), ER positivity (p=0.021), and PR positivity (p<0.001). There was a significant difference in tumor size when comparing lymph node positive and negative disease (19.06 mm vs. 13.11 mm, p<0.001). Conclusion: Age, tumor location, LVI, ER positivity, PR positivity, and larger tumor size are associated with lymph node involvement in cT1N0 HER2-positive breast cancers. Future research includes determining best practices to identify which patients in this population would benefit from neoadjuvant chemotherapy.

Citation Format: Laura DeCesare, Claudia Perez, Neha Nimmagadda, Yanyu Zhang, Samantha Terranella, Nicholas Skertich, Aaron Wiegmann, Andrea Madrigrano, Rosalinda Alvarado, Cristina O'Donoghue. Pathologic lymph lode status of patients with T1 HER2-positive breast cancer who did not receive neoadjuvant chemotherapy using the national cancer database [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS1-20.
Abstract PS1-25: Axillary management after neoadjuvant chemotherapy in initially node positive early breast cancer
Authors: Murillo Serafin Morales , Cudós Ariadna Gasol , Subirats Ona Pallisé , Olivé Jordi Melé , Morales Carles Canosa , Villellas Felip Vilardell , Guzman Douglas René Sanchez , Rodriguez Joel Veas , Galindo Alvaro Rodriguez
Published: February 2021

Response to neoadjuvant treatment could modify axillary management of those with node involvement at diagnosis. We investigated whether histological response correlates with node response and could avoid axillary dissection. A series of 339 patients with node positive early breast cancer who received neoadjuvant chemotherapy was analysed. We reported the axillary conversion (ypN0) rate and its association between clinical/pathological parameters. Median age was of 52 (24-89), median tumor size of 38mm; 120 (35%) patients were HER2 positive, 132 (39%) were luminal, and 87 (26%) were triple negative breast cancer. 113 (33%) patients obtained breast pathological complete response (breastpCR): 53/120 (44%) in HER2 positive, 21/132 (16%) in luminal and 39/87 (45%) in triple negative breast cancer. Axillary conversion to ypN0 rate was of 157/339 (46%): 71/120 (59%) in HER2 positive, 40/132 (30%) in luminal and 46/87 (53%) in triple negative breast cancer. It was found a 105/339 (31%) of relapse, and mean survival was of 147 months (CI 95% 134-159). Of 113 patients with breastpCR, 94 achieved axillary ypN0 (83%) (OD=12.8, p=0.000): 45/53 of breastpCR in HER2 positive (85%) (OD=8.8; p=0.069); 16/21 of breastpCR in luminal (76%) (OD=11.6; p=0.000); 33/39 (85%) of breastpCR in triple negative breast cancer (OD=14.8; p=0.002). Residual axillary involvement in breastpCR is reported in the table.Conclusion: Global axillary conversion in patients with breastpCR was of 83%; being HER2 and triple negative those with major association. BreastpCR could predict axillary conversion in triple negative breast cancer (OD=14.8; p=0.002) and the residual node involvement never was more than 3 positive nodes. These patients could avoid axillary dissection if an adequate sentinel node biopsy is performed.

Axillary conversion in breastpCRGlobal (113)HER2 (53)Luminal (21)TN (39)ypN094 (83%)45 (85%)16 (76%)33 (85%)1 node8 (7%)3 (5%)1 (5%)4 (10%)2 nodes1 (0.8%)001 (2.5%)3 nodes1 (0.8%)001 (2.5%)>3nodes9 (7.9%)5 (10%)4 (19%)0

Citation Format: Serafin Morales Murillo, Ariadna Gasol Cudós, Ona Pallisé Subirats, Jordi Melé Olivé, Carles Canosa Morales, Felip Vilardell Villellas, Douglas René Sanchez Guzman, Joel Veas Rodriguez, Alvaro Rodriguez Galindo. Axillary management after neoadjuvant chemotherapy in initially node positive early breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS1-25.
Abstract PS1-32: A multicentre prospective feasibility study of carbon dye tattooing of biopsied axillary node and surgical localisation in breast cancer patients
Authors: Goyal Amit , Puri Shama , Marshall Andrea , Valassiadou Kalliope , Hoosein Moin , Carmichael Amtul R , Erdelyi Gabriella , Sharma Nisha , Dunn Janet , York Joanne
Published: February 2021

Background: The primary aim of this prospective, multicentre feasibility study was to determine whether the biopsied axillary node in patients with breast cancer can be marked using black carbon dye and successfully identified at the time of surgery. Methods: We included patients undergoing needle biopsy of the axillary lymph gland. The biopsied node was tattooed at the time of needle biopsy (fine needle aspiration or core biopsy) or at a separate visit with black carbon dye (Spot™ or Black Eye™). Participants underwent primary surgery or neoadjuvant chemotherapy and axillary surgery (SNB or ALND) as per routine care. Results: 110 patients were included. Median age of the women was 59 (range 31 to 88) years. 48 of 110 (44%) underwent SNB and 62 (56%) ALND. The median volume of dye injected was 2.0 ml (range 0.2-4.2).Tattooed node was identified in 90 of 110 (82%) patients. The identification rate was higher (86%) in the primary surgery group compared with NACT (64%). Of those undergoing NACT, the identification rate was better in the patients undergoing SNB (3 of 4, 75%) compared with ALND (11 of 18, 61%). The tattooed node was the sentinel node in 78% (28 of 36) patients in the primary surgery group and 100% (3 of 3) in the NACT group. For surgeons who had performed ≥5 operations, there was no learning curve. The identification rate did not vary with body mass index or volume of dye injected. There was no correlation between volume of dye and number of tattooed nodes removed. Conclusion: It is feasible to mark the axillary node with carbon dye and identify it intraoperatively. Modifications of the technique, such as injecting the dye in the cortex alone, restricting the volume to 0.2 to 0.4 ml and combining with clip, will improve the technical ability to identify the marked node.

Citation Format: Amit Goyal, Shama Puri, Andrea Marshall, Kalliope Valassiadou, Moin Hoosein, Amtul R Carmichael, Gabriella Erdelyi, Nisha Sharma, Janet Dunn, Joanne York. A multicentre prospective feasibility study of carbon dye tattooing of biopsied axillary node and surgical localisation in breast cancer patients [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS1-32.
Abstract PS1-59: Skin and nipple sparing mastectomies - oncologic outcomes from an oncologic center
Authors: Costeira Beatriz , da Silva Francisca Brito , Oom Rodrigo , Costa Cristina , Moniz João Vargas , Alves Rui Serra , Abecasis Nuno , Santos Catarina Rodrigues
Published: February 2021

Introduction: Skin and Nipple Sparing mastectomies are an alternative for patients not eligible for conservative breast surgery, allowing for better aesthetic results than classical mastectomies. We aimed to evaluate oncological safety outcomes and identify risk factors for locoregional recurrence in patients submetided to sparing mastectomies. Methods: A retrospective analysis was conducted on all consecutive cases of skin sparing mastectomy (SSM) or nipple sparing mastectomy (NSM) for a primary diagnosis of invasive or in situ breast carcinoma, treated at an oncologic center, from january 2013 to may 2019. Primary outcome was locoregional recurrence. Secondary outcomes included overall survival and disease-free survival, median time to recurrence and median follow-up time. Risk factors for locoregional recurrence were analysed using chi-square test and t test where suitable, followed by a logistic regression model. Survival analysis was performed using Kaplan-Meier curve. Results: We included 461 cases; 59 cases (13%) presented with carcinoma in situ and 402 (87%) with invasive carcinoma. Median age was 46 (24-78) years. Seventy-one (15%) patients had locally advanced disease. SSM were performed in 226 (49%) cases and NSM in 235 (51%). Neoadjuvant chemotherapy was administered in 141 (31%) cases and adjuvant radiotherapy in 203 (44%). Locoregional recurrence rate was 3,4% with no nipple-areolar complex (NAC) recurrence. Median time to recurrence was 22 (1-54) months. Overall survival was 91,7% and disease-free survival was 80,4% at a median follow-up time of 39 (1-86) months.Factors associated with locoregional recurrence in univariate analysis were tumor size over 4cm, high histological grade, negative endocrine receptors, neoadjuvant chemotherapy and absence of endocrine therapy (p<0,05), however none of these factors were independently associated with recurrence as ascertained by logistic regression model. There was no association of recurrence with familial risk mutation. Conclusions: SSM and NSM present as a safe surgical approach to breast cancer requiring mastectomy, with a locoregional recurrence rate comparable to classical mastectomy. It was not identified a group of patients who are at risk of recurrence. Nonetheless, risk factors such as tumor size, histological grade, absence of endocrine receptors, neoadjuvant chemotherapy and absence of endocrine therapy may correlate with less favorable outcomes.

Citation Format: Beatriz Costeira, Francisca Brito da Silva, Rodrigo Oom, Cristina Costa, João Vargas Moniz, Rui Serra Alves, Nuno Abecasis, Catarina Rodrigues Santos. Skin and nipple sparing mastectomies - oncologic outcomes from an oncologic center [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS1-59.
Abstract PS10-13: Impact of trastuzumab on Ipsilateral breast tumor recurrence after breast conserving surgery
Authors: Cheun Jong Ho , Lee Han-Byoel , Moon Hyeong-Gon , Noh Dong-Young , Han Wonshink
Published: February 2021

Background: Trastuzumab is well known to be effective to control locoregional recurrence and distant metastasis of human epidermal growth factor receptor 2 (HER2)-overexpressing breast tumor. However, few studies have reported the effect of ipsilateral breast tumor recurrence (IBTR) in spite of higher incidence of IBTR for HER2 overexpressing subtype than other subtypes. The purpose of this study is to investigate the difference in the incidence of IBTR of HER2-overexpressing breast tumor according to adjuvant trastuzumab.

Methods: We retrospectively reviewed 996 patients who had done surgery for HER2-overexpressing breast cancer between January 2000 and December 2017 in our institution. Patients with tumors smaller than 0.5cm without axillar node metastasis were excluded. As regarding IBTR as recurrence “in” the ipsilateral breast, only patients who had done breast conserving surgery were included.

Results: There were 735 patients who had finished adjuvant trastuzumab as first planned and 555 patients with hormone receptor positive. Median follow-up period for all patients was 70.7 months (range 12.7-239.6 months). The 10-year IBTR-free survival rate showed a significant benefit for the group treatment with trastuzumab than the group without trastuzumab (97.0% versus 91.9%; p=0.007). In a multivariate analysis, presence of lymphovascular invasion (Hazard ratio [HR], 2.53; 95% Confidence interval [CI], 1.19 - 5.41), closed or involved resection margin (HR, 2.62; 95% CI, 1.20 - 5.74), positive hormone receptor (HR, 3.70; 95% CI, 1.69 - 8.08), positive axillar lymph node (HR, 5.21; 95% CI, 1.75 - 15.57), and omitted or uncompleted adjuvant trastuzumab (HR, 2.72; 95% CI, 1.11 - 6.67) were independent predictors of IBTR. However, subgroup analysis of the patients with hormone receptor negative tumor showed no benefit of adjuvant trastuzumab (98.1% versus 96.6%, p=0.669) while it controlled IBTR for hormone receptor positive tumor (95.7% versus 86.2%; p=0.002). When additionally analzyed, trastuzumab showed benefit for 10-year locoregional recurrence-free survival (95.5% versus 89.7%, p=0.012) and distant metastasis-free survival (93.5% versus 77.8%, p<0.001).

Conclusions: Trastuzumab has a clinical benefit in not only locoregional recurrence but also IBTR among HER2-overexpression breast cancer, especially with negative hormone receptor.

Citation Format: Jong Ho Cheun, Han-Byoel Lee, Hyeong-Gon Moon, Dong-Young Noh, Wonshink Han. Impact of trastuzumab on Ipsilateral breast tumor recurrence after breast conserving surgery [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS10-13.