bluuebunny/crossref_metadata_2025 huggingface dataset:
Multilevel Structural Characteristics of Jinshajiang Main Fault and Its Influence on Engineering
Authors: Zhou Hui , Shen Yihuan , Zhu Yong , Han Gang , Zhang Chuanqing , Zhang Ning
Published: March 2022

It is of great significance to study the geological characteristics of faults and the corresponding displacement patterns for the tunnel engineering crossing active faults. On the basis of field investigation and geological data analysis, it is found that the secondary weak structures, such as narrow cleavage bands, narrow joint bands, fault gouge zones, and small folds, often appear in the fault fracture zones and affected zones. The multilevel structure of fault is proposed from mechanics and engineering by summarizing their main characteristics. Taking the outcrop of fracture zones of Batang section, Jinshajiang main fault in the Qinghai-Tibet Plateau as the research object, the geometric characteristics of rock masses, the particle size, mineral composition, and mechanical characteristics of rocks in the fault are studied through field investigation, geological mapping, mineral composition analysis, and mechanical tests. In addition, a displacement model of multilevel structure fault is presented by numerical simulation. The results show that the Jinshajiang main fault comprises a primary structure and several secondary weak structures, which has a typical structure of multilevel fault. There are several secondary weak structures in the outcrop of the fracture zone. Compared with the rock masses in the primary structure, the joints of the rock masses in the secondary weak structure are more developed, and the rock particle size is smaller, the mud content is higher, and the mechanical strength is lower. The geometric morphology, mineral composition, and mechanical properties of the rock masses in the secondary weak structure are obviously different from those of the primary structure. The overall displacement mode of multilevel structural fault is S-shaped distribution, and the secondary weak structure will affect the displacement distribution pattern and have the possibility of sliding when the fault moves. Therefore, the secondary weak structure section in the tunnel should be a priority for prevention and control when designing tunnels through active faults. The multilevel structure of the fault, together with centralized structure, distributed structure, and stepped structure of the fault, can be used as a structure classification method of fault structure, which provides a reference for the study of disaster mechanisms, and prevention and control measures of tunnels crossing active faults.
Analysis of Emotional Education Infiltration in College Physical Education Based on Emotional Feature Clustering
Authors: Wang Zhengfa , Wang Junheng
Published: March 2022

Integration of emotional education physical education research in colleges and universities is a topic that has both theoretical and practical implications. Teachers in physical education should pay attention not only to the development of students’ physical knowledge and skills but also to their emotional education, emphasizing the positive role of emotional factors. Emotion is a type of internal experience that people have when deciding whether or not objective things can meet their needs. The diversity of emotional needs, the contradiction of emotional experience, the singleness of emotional orientation, and the universality of negative emotions are all new characteristics of contemporary college students’ emotional development. A teaching feedback strategy generation algorithm based on the emotional learning ontology is designed to obtain the students’ perception and understanding of the learning process without the need for question-and-answer interaction with the students. Based on “emotional triggers,” a better understanding of students’ learning status can be provided, as well as better cognitive and emotional support. The main measure and means to improve teaching quality and efficiency in physical education is to combine cognition, emotion, and education. This paper discusses the connotation and scope of emotional education in colleges and universities and proposes ideas for strengthening emotional education in colleges and universities in light of the new characteristics of college students’ emotional development, based on the clustering of emotional features, in terms of emphasizing the emotional influence of teachers, bolstering students’ aesthetic education, and exploring new avenues for college students’ emotional education.
A Robust Detection Method for Multilane Lines in Complex Traffic Scenes
Authors: Song Xiang , Che Xiaoyu , Jiang Huilin , Yan Shun , Li Ling , Ren Chunxiao , Wang Hai
Published: March 2022

The robustness and stability of lane detection is vital for advanced driver assistance vehicle technology and even autonomous driving technology. To meet the challenges of real-time lane detection in complex traffic scenes, a simple but robust multilane detection method is proposed in this paper. The proposed method breaks down the lane detection task into two stages, that is, lane line detection algorithm based on instance segmentation and lane modeling algorithm based on adaptive perspective transform. Firstly, the lane line detection algorithm based on instance segmentation is decomposed into two tasks, and a multitask network based on MobileNet is designed. This algorithm includes two parts: lane line semantic segmentation branch and lane line Id embedding branch. The lane line semantic segmentation branch is mainly used to obtain the segmentation results of lane pixels and reconstruct the lane line binary image. The lane line Id embedding branch mainly determines which pixels belong to the same lane line, thereby classifying different lane lines into different categories and then clustering these different categories. Secondly, the adaptive perspective transformation model is adopted. In this model, the motion information is used to accurately convert the original image into a bird’s-eye view image, and then the least-squares second-order polynomial fitting is performed on the lane line pixels. Finally, experiments on the CULane dataset show that the proposed method achieved similar or better performance compared with several state-of-the-art methods, the F1 score of the proposed method in the normal test set and most challenge test sets is better than other algorithms, which verifies the effectiveness of the proposed method, and then the field experiments results show that the proposed method has good practical application value in various complex traffic scenes.
The Study on the Characteristics of Pressure Arch above the Twin‐Parallel Openings in the Jointed Rock Masses
Authors: Gao Kunpeng , Liang Kang , Wang Leyao , Li Changhao , Yu Jinghai , Wu Runyi
Published: March 2022

The self‐bearing capacity of the rock masses has been a hot pot in the research of supporting technology in underground engineering. The pressure arch has been considered the main hypothesis to explain the self‐bearing capacity of the rock masses. In this paper, the engineering of the twin‐parallel openings in the jointed rock masses was selected as the background of the research. The characteristics of the deformation or the movement of the rock masses above the openings were studied based on the pressure arch theory. The difference between the single opening and the twin‐parallel openings has been revealed, and the mechanism has also been illustrated. Besides, the joints’ strength, the in situ stress ratio, the distance between the two openings, and the excavation sequence were selected as the variable parameters, and their influences have also been illustrated by the DEM method.
Research on the Teaching Method of Environmental Landscape Design Practice Based on IoT Network and Digital VR Technology
Authors: Yang Bo , Huadong Liu
Published: March 2022

The traditional practical teaching methods are based on teachers’ narration and demonstration, with few practical opportunities for students, lack of interactivity in teaching, low interest of students in teaching, and poor teaching effect. In order to improve the teaching effect of environmental landscape design and enhance students’ learning enthusiasm, a practical teaching method of environmental landscape design based on IoT network and digital VR technology will be studied. After guiding students to carry out the cognitive construction of environmental landscape design, VR technology is used to establish virtual teaching scenes for students. To create effective virtual reality engagement in the teaching process and enable students to better grasp important design information, gesture recognition technology is employed to recognize students’ landscape design operations. After the application of the proposed teaching method in teaching was verified through examples, the students’ learning interest was significantly increased, and the excellent rate of students’ design works was increased by about 16.6%, with good teaching effect.
A Dual-Network Modeling Architecture for Statistical Evaluation of College Graduates’ Working Ability in Consistence with Their Job Position and Remuneration
Authors: Hong Shaoyong , Yang Chun , Wen Hongwei , Song Chao , Shi Jincheng , Chen Shaohong , Hu Xiaoyu
Published: March 2022

Optimal human resources allocation asks to employ a person to work in the position corresponding to his/her ability. Employment competence is the key feedback to the cultivation of college students’ working ability. The data relationship needs to analyze between the in-school cultivation items and the working abilities required by the companies. Machine learning framework is introduced to study the companies’ responses to the cultivation of college students. In this work, a dual-network architecture is built up for statistical modeling evaluation of college graduates’ working ability in consistence with their job position and remuneration. A requirement network and a cultivation network are constructed for extracting features from the original working ability data required by companies and cultivated ever in school. The networks are fully trained by adaptively tuning the linking weights. The extracted features are fused together to estimate the working competence of each target sample/person. To evaluate the dual-network model, a modeling index system is designed, including proposing a total evaluation index calculus for the dual-network model, and a variable importance index from the original data. The samples are consequently ranked by the model predicted index and by the variable importance index, respectively. The ranking difference is used to evaluate the prediction efficiency of the dual-network model. Experimental results show that the dual network architecture is feasible to establish statistical models for the evaluation of college graduates’ in-school cultivated working ability in consistence with the company’s required working ability at their job position and their deserved remuneration.
Research on Comprehensive Evaluation of Economic Management Performance Based on Improved Fuzzy Clustering Algorithm
Authors: Xian Shi
Published: March 2022

In order to solve the problems of low recall rate and precision rate, high error rate, and long evaluation time in traditional evaluation methods, a comprehensive evaluation of economic management performance based on an improved fuzzy clustering algorithm is designed. The improved magnetic optimization algorithm was used to optimize the fuzzy C-mean algorithm, the improved fuzzy clustering algorithm was completed, and the improved fuzzy clustering algorithm was used to mine the economic management performance data. Using data mining findings and AHP’s weighting formula, a complete method for evaluating economic management effectiveness was developed. The BP neural network was improved using a genetic algorithm based on the index weight calculation findings, and the full-assessment model of economic management performance was constructed. Using this approach, it is possible to accurately and quickly assess the economic management performance of a company with a high rate of recall and accuracy; the error rate of a thorough assessment ranges between −3 percent and 4 percent; the average duration for an assessment is 0.81 seconds.
Research on Massive Image Retrieval Method of Mobile Terminal Based on Weighted Aggregation Depth Feature
Authors: Zhao Guotao , Ding Jie
Published: March 2022

Image self-coupling and feature interference lead to poor retrieval performance in massive image retrieval of mobile terminals. This paper proposes a massive image retrieval method of mobile terminals based on weighted aggregation depth features. The pixel big data detection model of massive images of mobile terminals is constructed, the collected pixel information of massive images of mobile terminals is restructured, the edge contour feature parameter set of massive images of mobile terminals is extracted, the feature fusion processing of massive images of mobile terminals is carried out in gradient pixel space by means of feature reconstruction and gray moment invariant feature analysis, the depth feature detection of massive images of mobile terminals is realized by using weighted aggregation method, the gradient value of pixels of massive images of each mobile terminal is calculated, and the optimized retrieval of massive images of mobile terminals is realized according to the fusion result of gradient weighted information. Simulation results show that this method has better feature clustering, stronger image detection and recognition, and anti-interference ability and improves the precision and recall of image retrieval.
The Relationship between Thyroid-Stimulating Hormone and Insulin Resistance in Incipient Elderly Type 2 Diabetics with Normal Thyroid Function
Authors: Zhang Yajing , Zhang Lin
Published: March 2022

Objective. To explore correlations between serum thyroid-stimulating hormone (TSH) concentration within the normal range and insulin resistance and its possible mechanism in incipient type 2 diabetes in elderly patients. Methods. 453 elderly patients with type 2 diabetes were divided into four groups by the quartile of TSH. Body mass index (BMI), waist-to-hip ratio (WHR), fasting plasma glucose (FPG), fasting insulin (FINS), homeostasis model assessment of insulin resistance (HOMA-IR) and homeostasis model assessment of insulin secretion (HOMA-β), blood lipids, and other indicators were compared among all groups, and correlation and regression analysis were conducted. 3T3-L1 preadipocytes were induced into mature adipocytes in vitro, and different concentrations of bovine TSH were used to stimulate adipocytes. The levels of TNF-α in the culture medium were detected by ELISA. Results. (1) With the increase of TSH, TC showed an increasing trend. Compared with the G1 group (4.80 ± 1.08), G2 group (5.13 ± 1.16), G3 group (5.14 ± 1.39), and G4 group (5.38 ± 1.16), the difference was statistically significant (

P
<
0.05

or

P
<
0.01

). The LDL also showed an increasing trend. Compared with the G4 group (3.47 ± 0.89), the G1 (3.12 ± 0.82) and G2 groups (3.14 ± 1.05) had a lower LDL, and the difference was statistically significant (

P
<
0.01

). The BMI increased between the G4 group (26.7 ± 3.97) and the G1 group (25.6 ± 3.54), and the difference was statistically significant (

P
<
0.05

). (2) The serum TSH level was positively correlated with FPG, FINS, HOMA-IR, TC, and LDL (R = 0.292, 0.271, 0.394, 0.195, and 0.178, all

P
<
0.01

). (3) TSH is the dependent variable, other indicators are independent variables, and multiple stepwise regression analysis is performed; the results show that only HOMA-IR, TC, and LDL enter the regression equation. (4) The TSH stimulated TNF-α secretion of 3T3-L1 adipocytes in a dose-dependent manner. Conclusion. The TSH level was positively correlated with the insulin resistance and LDL in the elderly incipient type 2 diabetic patients. Higher levels of TSH may be involved in the development of insulin resistance in the elderly incipient type 2 diabetic patients.
Influence of Arch Foot Defect of Primary Support on Mechanical Behaviors of an Arch Frame in Underground Tunnels
Authors: Wang Yakun , Guo Junwei , Zhao Jizeng , Yang Xuxu , Li Weiteng , Liu Junfeng
Published: March 2022

During the blasting excavation of the large-span tunnels, the instability of the blasting caused the overexcavation phenomenon, making the grille arch difficult to land completely in the primary support of the tunnel, thus forming an arch foot defect. In order to reduce the security issues of tunnel engineering construction and scientifically evaluate the influence of arch foot defects on the force performance of the overall structure of the arch frame, combining the Qingdao Metro long-span hard rock tunnel project, this paper designs two grille arch test sections with arch foot defects and one conventional section to carry out field tests. Combining with FLAC3D numerical simulation, the results of the study were used for analyzing the stress characteristics of arch foot defect grille arch in the primary support of the tunnel. The results indicated that (1) the arch foot of conventional section arch frame is subjected to the force transferred from the upper part and the deformation pressure of surrounding rock within the arch foot range, and the upper transfer force borne by the arch foot mainly comes from the deformation of arch waist. (2) When the arch frame has arch foot defects, the deformation of surrounding rock at the arch foot and the deformation transferred from the upper part mainly depend on the shotcrete, thus resulting in the increase of shotcrete strain. (3) Anchoring bolt and shotcrete can integrate the grid arch with the surrounding rock, thus bearing local loads in the arch crown, arch waist, and shotcrete. (4) The numerical calculation of arch frame with arch crown, arch waist, and arch foot defects claims that the force reduction of the arch frame caused by the arch foot defect was the most obvious, and the calculation results were consistent with the actual project.
Copper Oxide Nanoparticle‐Decorated Carbon Nanoparticle Composite Colloidal Preparation through Laser Ablation for Antimicrobial and Antiproliferative Actions against Breast Cancer Cell Line, MCF‐7
Authors: Mohammed Salman A. A. , Khashan Khawla S. , Jabir Majid S. , Abdulameer Farah A. , Sulaiman Ghassan M. , Al-Omar Mohsen S. , Mohammed Hamdoon A. , Hadi Aseel A. , Khan Riaz A.
Published: March 2022

Copper oxide (CuO) nanoparticle‐ (NP‐) decorated carbon NPs (CNPs) were produced as colloidal suspension through pulsed laser ablation technique in liquid (PLAL) medium. The antimicrobial activity of the produced NPs was tested against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli), and anticancer activity was tested against breast cancer cell line, MCF‐7, together with the biocompatibility assessment of these NPs. The X‐ray diffraction (XRD) patterns of the obtained CNPs showed peaks at 26.58° and 43.78° (2θ) identical to (002) and (111) planes, respectively, of the carbon phases. It also displayed new peaks at 38.5° and 48.64° (2θ) after doping with CuO NPs. Transmission electron microscope (TEM) images revealed the crystalline nature with the spherical shape of the prepared CNPs with 5‐40 nm diameter ranges. In addition, the NP effects on the bacterial cell walls and nucleic acid were confirmed using a scanning electron microscope (SEM) and microscopic fluorescence analysis. The NPs showed antibacterial activity through SEM examinations against the pathogenic microbial species, S. aureus and E. coli. In the cellular material release assay, the optical density of the bacterial cells, treated with NPs, displayed a significant increase with the time of exposure to NPs, and the cytotoxicity reached more than 80% of the level for the CNPs decorated with CuO NPs. The morphology of the MCF‐7 cells treated with NPs decreased numbers, and the loss of contact with the surrounding cells was observed. These results confirmed that the CNPs decorated with CuO NPs have no observable side effects and can be safely used for therapeutic applications. It is also noteworthy that it is the first report of preparation of CuO NPs decorated with CNPs (CuO NPs‐CNPs) by PLAL, and the produced NPs showed antimicrobial antiproliferative activities against breast cancer cell lines, MCF‐7. The main advantage of the PLAL technique of synthesizing CuO NPs‐CNPs provided a two‐step, cost‐effective, and eco‐friendly method.
Detection Method of Compound Chemical Material Hole Based on Deep Learning Image
Authors: Chen Jiajian , Zu Yuwei , Yang Jiapeng
Published: March 2022

As the degree of industrialization is getting higher and higher, the requirements for the accuracy of materials are getting higher and higher. Among them, the detection of round holes in materials is particularly important. Round hole inspection is one of the important methods for material forming and precision inspection. This paper studies the round hole detection method of composite chemical materials and aims at using deep learning image technology to provide an efficient and convenient detection method for round hole detection. This paper proposes a fast circular hole detection algorithm based on contour extraction and validity judgment. The algorithm can extract the circular holes on the material sufficiently and quickly, and the image recognition technology based on deep learning can effectively improve the accuracy and efficiency of circular hole detection. Whether it is in circular contour extraction, validity analysis, or parameter calculation, the improved algorithm has shown good results. The experimental results show that the improved algorithm is significantly better than the canny algorithm for the extraction of circular hole contours. In terms of effectiveness, the calculation time of the improved algorithm is lower than the original algorithm in different data sets, and the highest is 1.14 seconds lower than the original algorithm. The error in parameter calculation is also the lowest, and the error of a set of data is as low as 0.1%.
Abstract ES11-2: Macro and Micro: Macrophage and microbiome diversity in the breast cancer microenvironment
Authors: Guerriero JL
Published: March 2022

The breast tumor microenvironment (TME), devoid of nutrients and oxygen, recruits tumor associated macrophages (TAMs) that promote angiogenesis, metastasis and tumor growth. Removal or conversion of TAMs to an anti-tumor phenotype enhances chemo- and immuno-therapy in pre-clinical models and establishes TAMs as targets for anti-cancer therapy. Translation to the clinic has been slow, likely because current strategies broadly target macrophages. Several subsets of TAMs have been identified, yet little is known about their subset diversity in breast cancer and response to therapy. The failure to characterize TAM subsets has likely hindered progress in therapeutic targeting. This educational talk will provide a broad overview of the diversity of TAMs as well as the microbiome and how they are potentially intertwined within the complex breast TME. The talk will incorporate the state of the field to include elucidating the complexity of TAMs in breast cancer including their ontogeny, tissue specificity, phenotype, subset diversity and spatial relationship within the breast tumor. In addition, how the tumor microbiome may influence myeloid function and phenotype will be explored.

Citation Format: JL Guerriero. Macro and Micro: Macrophage and microbiome diversity in the breast cancer microenvironment [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr ES11-2.
Abstract ES12-1: Monitoring of advanced breast cancer with liquid biopsies
Authors: Bidard F
Published: March 2022

This talk will focus on the currently available data supporting the validity and utility of circulating tumor DNA for the monitoring and management of metastatic breast cancers, and provide a perspective on future developments.

Citation Format: F Bidard. Monitoring of advanced breast cancer with liquid biopsies [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr ES12-1.
Abstract ES2-1: Everything you always wanted to know about AI but were afraid to ask
Authors: Barzilay R
Published: March 2022

In this talk, I will introduce the audience to the foundations of artificial intelligence and its application to breast cancer diagnostics and care. By nature, many of the traditional clinical tasks such as risk assessment, prediction of treatment efficacy and forecasting patient trajectory can be thought of as prediction problems. Given sufficient amounts of patient data with outcomes, a machine learning model can make predictions which often exceed in accuracy human experts. However, to make these tools more applicable in the clinical setting, we need to augment AI models with the ability to explain their decisions to humans, and assess their uncertainty. In my talk, I will give multiple examples of deployed AI applications, analyzing their strengths and weaknesses. First, I will describe a natural language processing system for extracting tumor information from pathology reports. Next, I will talk about image-based AI models for risk assessment and early detection of breast cancer. Finally, I will summarize AI drug discovery methods for personalized medicine.

Citation Format: R Barzilay. Everything you always wanted to know about AI but were afraid to ask [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr ES2-1.
Abstract ES6-2: CDK4/6 for ER+
Authors: Mayer IA
Published: March 2022

Hormone receptor positive (HR+) breast cancer is the most common subtype of breast cancer. A reasonable proportion of HR+ tumors recur during or following adjuvant endocrine therapy, and late recurrences (beyond 10 years from diagnosis) are not uncommon. The CDK4/6 inhibitors palbociclib, ribociclib and abemaciclib were approved in combination with endocrine therapy for the treatment of first and second-line metastatic HR+ breast cancer, based on impressive improvements in progression-free survival and overall survival. Therefore, transitioning these drugs to the adjuvant setting in high-risk patients made sense, to further prevent short and long-term metastatic recurrence of HR+ breast cancer. To date, 3 of the 4 phase III clinical trials with CDK4/6 inhibitors in the adjuvant setting have been reported, with mixed results. Penelope-B and PALLAS, both exploring the use of palbociclib for 1 and 2 years, respectively, along with endocrine therapy in patients with high-risk clinical characteristics failed to demonstrate a benefit in 4-years and 2-years disease-free survival (DFS), despite an early signal of benefit in the Penelope-B trial at 2-years. The Monarch-E trial, using abemaciclib for 2 years along with endocrine therapy for patients with very high anatomical and biologic recurrence risk, has shown a 3% higher 2-years DFS than endocrine therapy alone, but follow-up is quite short (19 months), and it is unclear if it will be maintained over time. The NATALEE trial, using ribociclib for 3 years with endocrine therapy is expected to yield results in 2025. These data highlight several questions that remained unanswered. Are the CDK4/6 inhibitors different from each other despite an identical mechanism of action? Does duration of treatment matter? Does disease biology matter? Discontinuation rates, albeit different between these trials, seems to be an unlikely answer for the discrepant results. Fortunately, all these adjuvant trials have collected a rich biorepository of tissue and blood, which allows the investigators to better ellucidate unique biomarkers that may predict individual benefit for each of the approved CDK4/6 inhibitors, that will hopefully guide optimal patient selection and treatment combinations. Till then, longer follow-up on the Monarch-E and NATALEE trials are necessary to explore if CDK4/6 inhibitors should or not be incorporated to endocrine therapy in the adjuvant setting for patients at high-risk of metastatic recurrence.

Citation Format: IA Mayer. CDK4/6 for ER+ [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr ES6-2.
Abstract MS1-2: Genomics of DNA repair defects in breast cancer
Authors: Nik-Zainal S
Published: March 2022

While driver mutations in cancer genomes were the focus of cancer research for a long time, passenger mutational signatures - the imprints of DNA damage and DNA repair processes that have been operative during tumorigenesis - are also biologically informative. In this lecture, I provide an update of what has been uncovered in breast cancers in relation to genomic imprints of DNA repair defects and showcase how we have developed computational applications that we hope to translate toward clinical utility.

Citation Format: S Nik-Zainal. Genomics of DNA repair defects in breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr MS1-2.
Abstract OT1-14-02: Phase 3 study of trastuzumab deruxtecan (T-DXd) with or without pertuzumab vs a taxane, trastuzumab and pertuzumab in first-line (1L), human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (mBC): DESTINY-Breast09
Authors: Tolaney Sara M , Barroso-Sousa Romualdo , Jiang Zefei , Park Yeon Hee , Rimawi Mothaffar , Saura Cristina , Schneeweiss Andreas , Toi Masakazu , Yu Tinghui , Shetty Jagdish , Herbolsheimer Pia , Loibl Sibylle
Published: March 2022

Background: A combination of a taxane, trastuzumab, and pertuzumab (THP) is the standard-of-care (SOC) 1L treatment for patients (pts) with HER2+ mBC; THP demonstrated median progression-free survival (mPFS) of 18.7 mo and overall survival (OS) of 56.5 mo (Swain et al. N Engl J Med. 2015;372:724-734). However, pts eventually develop resistance to treatment. Novel treatment options are necessary in order to delay the emergence of resistance and provide better clinical outcomes, improve quality of life (QOL), and prolong survival in the 1L setting. T-DXd has demonstrated efficacy in pts with heavily pretreated HER2+ mBC, with an objective response rate (ORR) of 61.4%, duration of response (DOR) of 20.8 mo, and mPFS of 19.4 mo (Modi et al. Cancer Res. 2021. Abstract PD3-06). Data from DESTINY-Breast01 supported global approvals of T-DXd in HER2+ mBC. Here we describe a phase 3 trial evaluating the efficacy and safety of T-DXd ± pertuzumab compared with THP in the 1L treatment of HER2+ mBC. Trial design: DESTINY-Breast09 (NCT04784715) is a global, multicenter, randomized, phase 3 trial assessing the efficacy and safety of T-DXd with or without pertuzumab compared with SOC THP as 1L treatment in pts with HER2+ (IHC 3+ or ISH+ assessed locally per ASCO-CAP guidelines and centrally confirmed) advanced or mBC. This study consists of 3 treatment arms: arm A (T-DXd + placebo), arm B (T-DXd + pertuzumab), and arm C (THP). Randomization is 1:1:1 and pts will be stratified by prior treatment status (de novo vs recurrent), hormone receptor status (positive vs negative), and PIK3CA mutation status (detected vs not detected). Pts (N≈1134) must have had no prior chemotherapy or HER2-targeted therapy for advanced or mBC (1 prior line of endocrine therapy is allowed for mBC). The primary endpoint is PFS by blinded independent central review. Secondary endpoints include PFS by investigator assessment, OS, ORR, DOR, PFS2, health-related quality of life (QOL), pharmacokinetics, immunogenicity, and safety.

Citation Format: Sara M Tolaney, Romualdo Barroso-Sousa, Zefei Jiang, Yeon Hee Park, Mothaffar Rimawi, Cristina Saura, Andreas Schneeweiss, Masakazu Toi, Tinghui Yu, Jagdish Shetty, Pia Herbolsheimer, Sibylle Loibl. Phase 3 study of trastuzumab deruxtecan (T-DXd) with or without pertuzumab vs a taxane, trastuzumab and pertuzumab in first-line (1L), human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (mBC): DESTINY-Breast09 [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr OT1-14-02.
Abstract OT1-16-01: A multicenter phase II study of vaccines to prevent recurrence in patients with HER-2 positive breast cancer
Authors: Han Hyo S , Disis Mary , Wesolowski Robert , Fisher Carla , Gandhi Shipra , Chan Nancy , Gwin William , Gogineni Keerthi , Mick Rosemarie , Rodriguez Christina Sierra , Hogue Deanna , Liu Hien , Costa Ricardo , Czerniecki Brian
Published: March 2022

Background: HER2-positive breast cancer patients are commonly treated with neoadjuvant therapy including HER2-targeted therapy. Patients who have residual invasive disease have less favorable outcomes with an increased risk of recurrent disease than patients with complete pathologic response (pCR). It has also been observed that these non-pCR patients have low or absent anti-HER-2 CD4 Th1 responses. We hypothesized that correcting the anti-HER-2 CD4 Th1 response using vaccines will increase interferon gamma production which we have shown is a potent inducer of apoptosis and senescence in HER2-positive breast cancer. This study will be evaluating safety and immunogenicity of two vaccines (multivalent anti-oncodriver DNA vaccine (WOKVAC) or HER-2-pulsed dendritic cell vaccine (DC1)). Methods: This is a multi-center, phase 2, randomized study to determine the safety and tolerability of HER2 vaccines (DC1 and WOKVAC), assess immunogenicity, and evaluate recurrence free survival. Patients with HER2-positive early breast cancer (stage I-III) are eligible if they have residual invasive disease in the breast or axilla at surgery after receiving neoadjuvant chemotherapy plus HER2 -targeted therapy. Patients are randomly assigned in a 1:1 ratio to receive 1 of 2 adjuvant HER2 vaccines, either DC1 or WOKVAC for 1 year. A permuted-block randomization scheme was used with stratification according to residual cancer burden (RCB) (1+2 vs 3). The primary end points are safety and immunogenicity (immune response rate measured by ELISPOT). Each treatment arm will be assessed separately. Any statistical comparison between arms is purely exploratory, as this study is neither designed nor powered for comparative hypotheses. Secondary endpoints include recurrence-free survival. Exploratory analyses include the assessment of prognostic and predictive biomarkers including circulating tumor cells, serum HER2 levels, and other immune markers. The enrollment began in 2018 and we plan to accrue the total of 110 patients. ClinicalTrials.gov Identifier: NCT03384914

Citation Format: Hyo S Han, Mary Disis, Robert Wesolowski, Carla Fisher, Shipra Gandhi, Nancy Chan, William Gwin, Keerthi Gogineni, Rosemarie Mick, Christina Sierra Rodriguez, Deanna Hogue, Hien Liu, Ricardo Costa, Brian Czerniecki. A multicenter phase II study of vaccines to prevent recurrence in patients with HER-2 positive breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr OT1-16-01.
Abstract OT2-10-01: The VIOLA study: Validating individualized breast cancer screening by offering a new link in access
Authors: Daily Anna
Published: March 2022

The VIOLA Study is a Clinical Utility Study designed to investigate the useability of Melody®, a tear-based screening assay for breast cancer developed and validated by Namida Lab, Inc., a high complexity CLIA certified lab. It is well established that disparities exist in breast health, preventative care, and screening mammography. Namida Lab believes in the potential of Melody® to be a tool that bridges the gap between underserved populations and positive health outcomes. As such, Namida Lab, Inc. is partnering with federally qualified health centers and large employers to evaluate the clinical utility of Melody®. Melody® consists of two parts: tear sample collection and clinical lab assay. Participants will have a tear sample collected at a study site. The clinical lab assay, Melody®, will be performed at Namida Lab, Inc. The results of the Melody® assay will be returned to the site clinician to be discussed with the participant. The administration of Melody® does not require additional appointments or trips and can be done by any member of a medical team. A minimum participation of 205 women who are 40 to 74 years of age, at average risk for developing breast cancer, asymptomatic, and have no concerns or breast abnormalities. To date 28 participants have been enrolled in the study. Study enrollment and eConsent will be conducted through our mobile application. Each participant will be required to take an enrollment survey that collects information on race, ethnicity, and socio-economic status. Participant's addresses will be obtained as part of the requisition process for the CLIA lab, from which information on geographic location can be obtained. In addition to the factors listed above, the enrollment survey also collects information on status and type of health insurance, reproductive health, breast health knowledge, prior screening history, and family and personal history of cancer The exit survey has been designed to collect information on the participant experience with Melody® and comprehension of the Melody® results relayed through their site clinician. In addition, information is collected on participant''s intention to schedule/participate in future screening mammograms and/or change in intention to participate in a previously scheduled screening mammogram. Primary endpoint: The VIOLA Study is designed to assess how incorporating Melody® into a primary care provider setting affects participation and confidence in the current breast health continuum of care. Secondary endpoint: Quantifying the relationship between Melody® and increased participation in breast health care offers the clinical utility evidence required for adoption into the Standard of Care.

Citation Format: Anna Daily. The VIOLA study: Validating individualized breast cancer screening by offering a new link in access [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr OT2-10-01.
Abstract P1-05-08: Targeting tumor heterogeneity and breast cancer metastasis through the metastatic microenvironment mediated epigenetic reprogramming
Authors: Yang Li , So Jae Young , Skrypek Nicolas , Merchant Anand , Nelson George , Yang Howard , Lee Maxwell
Published: March 2022

Targeting tumor heterogeneity and breast cancer metastasis through the metastaticmicroenvironment mediated epigenetic reprogrammingLi Yang and Jae Young So, Nicolas Skrypek, Anand Merchant, George Nelson, Howard H.Yang, Maxwell P. LeeNational Cancer Institute, National Institutes of Health, Bethesda, MD 20892Current cancer treatments are largely based on the genetic characterization of primarytumors and are ineffective for metastatic disease. There is lack of mechanistic understanding ashow cancer cells are selected and evolved to establish distant metastatic colonies. In addition,tumor heterogeneity and biomarker identification remain to be some of the most difficultchallenges in cancer treatment. In the current study, we discovered an increased DNAmethyltransferase 3B (DNMT3B) in metastatic nodules and in tumor cells with epithelia tomesenchymal (EMT) phenotype. Of great interest, high levels of DNMT3B were correlated withpoor clinical outcomes in multiple human breast cancer datasets. Mechanistically, DNMT3Balters multiple pathways including STAT3, NFkappaB, PI3K/Akt, beta-catenin, Notch signalingas well as EMT, which are critical for cancer cell survival, apoptosis, proliferation, invasion, andcolonization. We further identified PGE2 and IL6 as critical inflammatory mediators inDNMT3B induction. Importantly, targeting IL6 or PGE2 production reduced DNMT3Bexpression and improved chemo treatment or PD1 immune therapy. Furthermore, perioperative(surgical removal of primary tumors) targeting DNMT3B in combination with chemotherapymarkedly suppressed tumor recurrence and metastasis in preclinical mouse models for triplenegative breast cancer. Our studies identify DNMT3B as an important mechanism fortranscription regulation in tumor heterogeneity that is critical for tumor invasion and metastasis,thus suggesting a validated target for treating metastatic disease.

Citation Format: Li Yang, Jae Young So, Nicolas Skrypek, Anand Merchant, George Nelson, Howard Yang, Maxwell Lee. Targeting tumor heterogeneity and breast cancer metastasis through the metastatic microenvironment mediated epigenetic reprogramming [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-05-08.
Abstract P1-09-06: Insulinemic potential of diet and risk of total and subtypes of breast cancer among US women
Authors: Romanos-Nanclares Andrea , Willett Walter C. , Rosner Bernard A. , Tamimi Rulla M. , Tabung Fred K. , Holmes Michelle D. , Chen Wendy Y , Eliassen A. Heather
Published: March 2022

Background: Insulin resistance and hyperinsulinemia play important roles in the progression of multiple chronic disease and conditions. Diet modulates insulin response; however, evidence is limited regarding whether diet with higher insulinemic potential is associated with invasive breast cancer risk.Objectives: We prospectively evaluated the association between adherence to a food-based empirical dietary index for hyperinsulinemia (EDIH) and the incidence of invasive breast cancer.Methods: We prospectively followed 76,595 women from the Nurses’ Health Study (NHS, 1984-2016) and 93,295 women from the Nurses’ Health Study II (NHSII, 1991-2017). Diet was assessed by food frequency questionnaires every 4 years. The insulinemic potential of diet was evaluated using the EDIH that was pre-defined based on circulating C-peptide concentrations. Higher scores indicate higher insulinemic potential, while lower scores indicate lower insulinemic potential.Results: During 4,215,162 person-years of follow-up, we documented 10,595 breast cancer cases (6,639 NHS; 3,914 NHSII). Being in the highest, compared with the lowest, EDIH quintile was associated with higher breast cancer risk (HRQ5vsQ1 1.18; 95% CI 1.10, 1.27; P-trend<0.01). The association was suggestively strongest among women with current BMI<25 kg/m2 (HRQ5vsQ1 1.20; 95% CI 1.08, 1.34; P-trend<0.01; P-interaction=0.06) compared to overweight/obese women. Although heterogeneity by estrogen receptor (ER) status was non-significant (P=0.17), the strongest association between EDIH and breast cancer was observed with ER-negative tumors (HRQ5vsQ1 1.26; 95% CI 1.04, 1.51; P-trend<0.01). Among tumor molecular subtypes, the strongest associations were observed with HER2-enriched tumors (HRQ5vsQ1 1.75; 95% CI 1.08, 2.82; P-trend=0.01).Conclusions: A dietary pattern contributing to hyperinsulinemia was associated with greater breast cancer risk in women from the NHS/NHSII. In particular, a more hyperinsulinemic diet was associated with higher risk of breast cancer among lean women when compared to overweight or obese women. Moreover, the hyperinsulinemic diet showed a stronger positive association with ER-negative breast tumors, independent of adiposity. Our findings suggest that dietary interventions to reduce insulinemic potential may have a role in breast cancer prevention.

Citation Format: Andrea Romanos-Nanclares, Walter C. Willett, Bernard A. Rosner, Rulla M. Tamimi, Fred K. Tabung, Michelle D. Holmes, Wendy Y Chen, A. Heather Eliassen. Insulinemic potential of diet and risk of total and subtypes of breast cancer among US women [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-09-06.
Abstract P1-13-07: De-escalation of five-year adjuvant endocrine therapy in patients with ER-low positive breast cancer: Propensity-matched analysis from a prospectively maintained cohort
Authors: Yu Keda , Cai Yuwen , Shao Zhiming
Published: March 2022

Background The standard 5 years of endocrine therapy has shown additional benefits when compared with short-term 2-3 years of treatment in patients with estrogen receptor (ER)-positive breast cancer; however, whether the long-term treatment is still necessary for ER-low positive (1%-10% by immunohistochemistry) breast cancer is unclear. Methods The prospectively maintained Breast Surgery Database of Fudan University Shanghai Cancer Center was used for this propensity-matched analysis. The primary endpoint was disease-free survival (DFS). Multivariate Cox regression and propensity score matching methods were performed to minimize bias. Hazard ratio (HR) with 95% confidence interval (CI) was calculated. All statistics were 2-sided. Results From 2012 to 2017, there were 22768 consecutive women with pathologically confirmed early-stage breast cancer and 1013 (4.45%) were identified as ER-low positive. Among them, 634 cases met the inclusion criteria and were divided into three groups: received no endocrine therapy (n=89); received 2-3 years of endocrine therapy (n=185); and received approximately 5 years of endocrine therapy (n=360). At a median follow-up of 65 months, there was no significant difference in DFS between patients who received 2-3 years and 5 years of endocrine therapy (HR, 0.82; 95% CI: 0.51-1.33; P=0.43). In the multivariate Cox regression analysis of the propensity score-matched samples, the DFS was not significantly better for patients who received 5 years of endocrine therapy than those receiving 2-3 years of treatment (HR, 0.74; 95% CI: 0.41-1.31; P=0.30). Conclusion Short-term 2-3 years of endocrine therapy might be an alternative for ER-low positive breast cancer instead of standard 5 years.

Citation Format: Keda Yu, Yuwen Cai, Zhiming Shao. De-escalation of five-year adjuvant endocrine therapy in patients with ER-low positive breast cancer: Propensity-matched analysis from a prospectively maintained cohort [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-13-07.