bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P2-11-25: A 10-gene signature to predict the prognosis of early-stage triple-negative breast cancer
Authors: Kim Chang Min , Park Kyong Hwa , Yu Yun Suk , Kim Ju Won , Park Jin Young , Lee Jeong Eon , Sim Sung Hoon , Seo Bo Kyoung , Kim Jin Kyeoung , Lee Eun Sook , Park Yeon Hee , Kong Sun-Young 
Published: March 2023

Abstract
Background: Triple-negative breast cancer (TNBC) is highly heterogeneous cancer and the most challenging subtype of breast cancer. And its prognosis is poor compared to the other subtypes. Unlike luminal type cancers, there is no valid biomarker to predict the prognosis of patients with early TNBC. To establish an elaborate therapeutic strategy for TNBC, biomarkers that accurately predict the prognosis and response to treatment are needed. Method: 184 patients with early stage TNBC (training cohort, n = 76; validation cohort, n = 108) were enrolled. Median Follow-up period was 51.5 months (range: 4.6-230.8) for training cohort and 58.3 months (range: 6.6-99.8) for validation cohort. Of the patients in training cohort, 13 patients had recurrence or metastasis. Of the patients in validation cohort, 23 patients had recurrence or metastasis. Using a HiSeq sequencer, RNA sequencing was conducted to analyze the gene expression profiles of tumor samples from TNBC patients. Gene signature was analyzed by combination of DEGs which found in gene expression profiles. Cross validation and meta-analysis were conducted as pre-validation. Meta-analysis was conducted using CBS probePINGS. To compare gene signature and other methods, PAM 50 call and TCR diversity analysis were investigated. Statistical analyses were conducted using R language (v.3.4.3). Result: To predict prognosis of recurrence or metastasis for TNBC patients, we identified the 10-gene signature (DGKH, GADD45B, KLF7, LYST, NR6A1, PYCARD, ROBO1, SLC22A20P, SLC24A3 and SLC45A4) that stratified patients with TNBC by risk score (sensitivity = 92.31%; specificity = 92.06%; accuracy = 92.11%) and validated in a cohort of separate institutions. Meta-analysis supported the biological relevance of the 10-gene signature to well-known driving pathways in TNBC. When compared with other potential biomarkers like PAM 50 call and T-cell receptor β diversity, the 10-gene signature was the only independent factor that can predict prognosis for invasive disease-free survival in multivariate analysis. Conclusion: Our novel findings can contribute to solving the diagnostic challenges in TNBC and the 10-gene signature may serve as a novel biomarker for risk-based patient care.
Citation Format: Chang Min Kim, Kyong Hwa Park, Yun Suk Yu, Ju Won Kim, Jin Young Park, Jeong Eon Lee, Sung Hoon Sim, Bo Kyoung Seo, Jin Kyeoung Kim, Eun Sook Lee, Yeon Hee Park, Sun-Young Kong. A 10-gene signature to predict the prognosis of early-stage triple-negative breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-11-25.
Abstract P2-11-30: Performance of tumor vascularity as a biomarker is correlated with the change of tumor vascularity after preoperative systemic treatment in patients with breast cancer
Authors: Choi Hyang Suk , Son Eun Ju , Noh Hany Hany , Cho In-Jeong Cho In-Jeong , Lim Seung Taek , Lee Jong-In , Han Airi 
Published: March 2023

Abstract
Background) Breast cancer is a leading cause of death worldwide. Tumor vascularity is a hallmark of cancer including breast cancer. However, targeting tumor vascularity did not show consistent benefit when applied in clinic. This study aimed to investigate in which group of patients can tumor vascularity be a prognostic factor and how does change of tumor vascularity play in this situation. Materials and methods) Female patients with breast cancer who received preoperative chemotherapy due to breast cancer between 2003 and 2018 at Wonju Severance Hospital, Korea, were included. Clinocopathological characteristics were collected. Hounsfield units(HU) on contrast-enhanced computed tomography(CT) was used as a marker indicating tumor vascularity. Tumor to aortic arch ratio(TAR) of HU on contrast enhanced CT was applied to enhance objectivity of measurement. Patients were categorized according to the cut-off values retrieved from the receiver operating characteristic curve. Kaplan-Meier curves were generated to compare recurrence-free interval (RFI) and overall survival (OS). Results) The final cohort included 162 patients with a mean age of 48.63±7.9 (30-69) years. Initial TAR was 0.38±0.103 (range, 0.184-0.946) and TAR after completion of preoperative systemic treatment was 0.29 0.094(0.677-0.298). Difference between TAR of immediate before surgery and first clinical presentation was -0.0860.094(-0.386 – 0.176). TAR was decreased in 122 (75.3%) patients. Initial TAR was significantly correlated with recurrence free survival(RFS)(p=0.002). However, TAR after preoperative systemic treatment (p=0.221) or delta TAR (area under receiver operating characteristics = 0.498) were not significant. Interestingly, initial TAR was significant only in patients with decreased TAR after preoperative systemic treatment(p=0.005). Conclusion) Tumor vascularity represented with HU was significantly related with patients’ survival only when tumor vascularity was decreased in response to systemic treatment. Considering no antiangiogenic agents were applied as preoperative systemic treatment and still capacity of tumor vascularity as a biomarker was influenced by the change of itself, antiangiogenic agents could be used as a complimentary agent for the other agents which also impact tumor vascularity.
Citation Format: Hyang Suk Choi, Eun Ju Son, Hany Hany Noh, In-Jeong Cho In-Jeong Cho, Seung Taek Lim, Jong-In Lee, Airi Han. Performance of tumor vascularity as a biomarker is correlated with the change of tumor vascularity after preoperative systemic treatment in patients with breast cancer. [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-11-30.
Abstract P2-21-11: A high content imaging and analysis approach to screen compounds for novel drug targets in 3D breast cancer co-culture model
Authors: Ali Rizwan , Huwaizi Sarah , Alsubait Arwa , Boudjelal Mohamed 
Published: March 2023

Abstract
The desired effect of cancer therapeutics can only be conceived when applied to complex multicellular structures with different cell types and extracellular matrix (ECM) in three-dimensional (3D) space. Therefore, 3D cell culture systems have become very popular in drug screening and discovery. There is an immense demand for highly efficient and easy methods to produce 3D spheroids in any cell format. However, heterogeneity in size, extended cultivation times, and reproducibility for high throughput assays are limiting factors in the generation of spheroids. Recently we have established a naturally transformed breast cancer cell line, KAIMRC1 (1), from ductal breast carcinoma. We have developed a novel and easy method to produce spheroids (2) from KAIMRC1 cells in vitro, which can be used as a 3D model to study proliferation, differentiation, metabolism, cell death, and drug response of cells in the tumor microenvironment. We developed an in-vitro high content imaging (HCI) based cellular assay using commercially available compound panels to perform initial drug screening in the KAIMRC1 spheroids model. Our approach allows rapid screening of a panel of drugs to assess inhibitory effects on the growth of tumor cells in 3D cultures. To mimic the actual in-vivo tumor microenvironment, we are now developing an HCI-based assay utilizing 3D KAIMRC1 spheroids co-cultured with patient-derived fibroblast cells. 1. Ali, Rizwan, et al. “Isolation and Characterization of a New Naturally Immortalized Human Breast Carcinoma Cell Line, KAIMRC1.” BMC Cancer 17 (2017) 2. Rizwan Ali et al., (2021) New Born Calf Serum (NBCS) can induce spheroid formation in breast cancer KAIMRC1 cell line. Front. Mol. Biosci. DOI: 10.3389/fmolb.2021.769030
Citation Format: Rizwan Ali, Sarah Huwaizi, Arwa Alsubait, Mohamed Boudjelal. A high content imaging and analysis approach to screen compounds for novel drug targets in 3D breast cancer co-culture model [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-21-11.
Abstract P2-23-05: Trastuzumab-Induced Tumor Microenvironment Changes in Early HER2+ Breast Cancer
Authors: Kennedy Laura C. , Alvarez Rebeca , Dintzis Suzanne , Gadi Vijayakrishna K. 
Published: March 2023

Abstract
Background Trastuzumab (H) is a critical component of therapy (tx) for HER2+ breast cancers (BCs) and can induce anti-tumor immune responses that as part of its mechanism of action. Pre-clinical studies have suggested that antibody-dependent cell-mediated cytotoxicity (ADCC) through NK cells is a major driver of the immune response. However, there is also evidence that macrophages and dendritic cells (DCs) can play an important role in H immune response through antibody-dependent cellular phagocytosis (ADCP). Here, we present pre- and post-tx gene expression and immunohistochemistry (IHC) data to characterize the tumor microenvironment (TME) changes in response to a single dose of H in patients (pts) with early HER2+ BC. Methods Pts with Stage I-III HER2+ BC with minimum 1 cm tumors were eligible. Pts received 8 mg/kg IV H followed by tissue collection. There was a minimum of 14 days between (btw) H and post-tx tissue collection. Pre- and post-tx tissues were assessed for tumor-infiltrating lymphocytes (TILs), immune-related gene expression, and AE1/3, CD31, CD4, CD8, CD11b, CD68, and CD56 expression through IHC. Results Thirteen pts were enrolled and evaluable. 5/13 were estrogen-receptor positive (ER+). TILs were assessed independently by two pathologists and the results averaged. Tx with H resulted in an increase in TILs in the post-tx tissue (p &lt; 0.01). Pre-tx TILs ranged from 2-80% (median 6%) and post-tx TILs ranged from 2-80% (median 20%). 6/13 pts had immune infiltration (Inf), defined as a TIL increase of greater than 1 decile btw pre- and post-tx samples. 2/6 pts with Inf were ER+. Pts with Inf had a significantly higher DC immune signature (ISS) compared to pts without Inf (p &lt; 0.01, univariate analysis). No other ISS reached significance. 6 pts had paired pre- and post-tx samples evaluated by IHC. 4/6 pts had Inf per prior definition. Pts with Inf had an increase in CD11b+ (includes macrophages and some DCs) and CD56+ cells (includes NK cells) after H tx within the tumor compartment (p &lt; 0.05). Pts with Inf had an increase in CD11b+, CD56+, and CD44+ cells in the stromal compartment (p &lt; 0.05). Conclusions Innate immune cells such as macrophages and DCs are key players in H-induced immune response in the early HER2+ BC TME. This data is consistent with prior pre-clinical findings.
Citation Format: Laura C. Kennedy, Rebeca Alvarez, Suzanne Dintzis, Vijayakrishna K. Gadi. Trastuzumab-Induced Tumor Microenvironment Changes in Early HER2+ Breast Cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-23-05.
Abstract P2-26-08: Influence of genetic ancestry on breast stromal cells provides biologic basis for increased incidence of metaplastic breast cancer in women of African descent
Authors: Kumar Brijesh , Batic Katie , Bhat-Nakshatri Poornima , Granatir Maggie , Addison Rebekah , Szymanski Megan , Baldridge Lee Ann , Temm Constance , Sandusky George , Althouse Sandra , Storniolo Anna Maria , Nakshatri Harikrishna 
Published: March 2023

Abstract
The biologic basis of genetic ancestry-dependent variability in disease incidence and outcome is just beginning to be explored. We recently reported enrichment of a population of ZEB1-expressing cells located adjacent to the ductal epithelial cells in the normal breast of women of African Ancestry (AA) compared to European Ancestry (EA). By establishing and characterizing cell lines corresponding to these cells and validating in vitro findings with tissue microarrays of healthy breast tissue from AA, EA and Latina Ancestry (LA) women, we demonstrate that these cells have the properties of fibroadipogenic/mesenchymal stromal cells that express PROCR and PDGFR. PROCR+/ZEB1+/PDGFR+ cells, hence renamed as PZP cells, are enriched in the normal breast tissues of AA compared to EA or LA women. In vitro, PZP cells trans-differentiated into adipocytes or osteocytes. In co-culture conditions, PZP:epithelial cell communication resulted in luminal epithelial cells acquiring basal/stem cell characteristics and increased expression of IL-6 suggesting the impact of this communication on the microenvironment and breast epithelial hierarchy. Consistent with this possibility, the level of phospho-STAT3, which is a downstream target of IL-6, was higher in the normal and cancerous breast tissues of AA compared to EA women. PZP cells transformed with HRasG12V ± SV40-T/t antigens generated metaplastic carcinoma in NSG mice suggesting that these cells could be the cell-of-origin of metaplastic breast cancers. Collectively, these results identify a stromal cell component that could influence the biology of breast cancer in AA women.
Citation Format: Brijesh Kumar, Katie Batic, Poornima Bhat-Nakshatri, Maggie Granatir, Rebekah Addison, Megan Szymanski, Lee Ann Baldridge, Constance Temm, George Sandusky, Sandra Althouse, Anna Maria Storniolo, Harikrishna Nakshatri. Influence of genetic ancestry on breast stromal cells provides biologic basis for increased incidence of metaplastic breast cancer in women of African descent [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-26-08.
Abstract P3-04-07: Safety and artifact testing of a nitinol breast biopsy clip in an ultra-high resolution magnetic resonance imaging (MRI) environment
Authors: Dong William , Ramchandran Kanchna , Galloy Adam , Nino Marco A. , Kleingartner Marla , Raghavan Madhavan L. , Phadke Sneha , Magnotta Vincent A. 
Published: March 2023

Abstract
Background: The lack of safety clearance of several metallic breast implants in 7T(Tesla) poses a significant hurdle to standard clinical breast cancer care and research from reaping the benefits of ultra-high resolution MR imaging. A breast biopsy clip (Ultracor Twirl, Becton, Dickinson and Company, Vernon Hills, IL) composed of nitinol, was tested for safety and artifact susceptibility clearance in a 7T MRI scanner, using standardized procedures. This clearance is significant in henceforth allowing patients with this implant to be scanned in now FDA approved ultra-high-field MRI scanners of 7T or less for clinical and research purposes. Methods: Tests for magnetic susceptibility (torque and translational attraction), MRI-related heating, and artifacts were conducted as per standardized protocols. The torque and translational attraction tests evaluated the effects of magnetic force by the MRI to cause the clip to move and twist respectively. The heating test was conducted with customized MR parameters of short TR (repetition time) and maximum echo-train length, designed to induce temperature change. The artifact test using T1 weighted spin and gradient echo imaging sequences, evaluated potential localized signal loss that may result in misrepresentation of the imaged area. This may occur due to the presence of the metallic clip in the MR environment. Results: The torque and translational attraction tests respectively indicated that the MR environment did not induce any movement in the clip in eight orientations, with a deflection angle of 0 degrees. Results of the heating test indicated no significant temperature change of the clip. A temperature change of less than 0.45C° was observed in the phantom gel in both the absence and presence of the clip, which is well within the safety threshold (&lt; 1°C). Results of the artifact test indicated a very small artifact, with the largest artifact cross-sectional area appearing on gradient echo images. Conclusion: These cumulative results indicate that the Ultracor Twirl breast biopsy clip is safe for imaging patients at 7T.
Citation Format: William Dong, Kanchna Ramchandran, Adam Galloy, Marco A. Nino, Marla Kleingartner, Madhavan L. Raghavan, Sneha Phadke, Vincent A. Magnotta. Safety and artifact testing of a nitinol breast biopsy clip in an ultra-high resolution magnetic resonance imaging (MRI) environment [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-04-07.
Abstract P3-04-11: Longitudinal Changes of Contralateral Breast Mammographic Artificial Intelligence Algorithms Score in Ductal Carcinoma In Situ patient with Tamoxifen
Authors: Lim Changjin , Park Eun Kyung , Kim Hong-Kyu , Kang Eunhye , Jung Ji-Jung , Yeoh Hyunsu , Kim Jang-il , Chun Jung Whan , Lee Han-Byoel , Moon Hyeong-Gon , Han Wonshik 
Published: March 2023

Abstract
Background Mammographic Artificial intelligence (AI) algorithms (Lunit insight MMG) draws attention as a diagnostic support tool for breast cancer detection. Lunit insight MMG provides a location suspected of breast cancer with a heatmap and a score reflecting the probability of the presence of suspicious areas. We investigated whether the Lunit insight MMG score is relevant for predicting the response to adjuvant tamoxifen. Methods Patients diagnosed with DCIS and underwent treatment at Seoul National University Hospital in 2010 were retrospectively enrolled. Clinical characteristics, tamoxifen use, survival data, and mammography images were extracted from the electronic medical records, and Lunit insight MMG scores were calculated retrospectively. We classified two groups according to tamoxifen treatment and compared the score change of contralateral breast from baseline to 5 years after surgery for DCIS. Change categories of Lunit insight MMG score included maintaining high risk, maintaining low risk, increasing from low risk to high risk, and decreasing from high risk to low risk. Results Of 100 patients, 50 (50%) had undergone tamoxifen treatment (group 1) and 50 (50%) had not (group 2). The median age of the patients was 48.4 years for group 1 and 51.5 years for group 2 (p=0.172). The median follow-up duration was 8.7 years for the whole cohort. Using Lunit insight MMG score, more patients in group 1 decreased in contralateral breast cancer (CBC) risk compared with group 2 (6.0% vs. 2.0%; P=.008). No patients in group 1 had an increase in CBC risk while 9 patients increased in group 2 (0% vs. 18.0%; P =.008). There was no ipsilateral breast cancer recurrence for the whole cohort, and two patients experienced contralateral invasive breast cancer in group 2. In two patients with CBC, the Lunit insight MMG score increased five years after surgery, one year and three years before the CBC diagnosis. Conclusions Longitudinal Changes of Mammographic AI algorithms Score may be a predictive surrogate marker for response to tamoxifen therapy in hormone receptor-positive DCIS.
Citation Format: Changjin Lim, Eun Kyung Park, Hong-Kyu Kim, Eunhye Kang, Ji-Jung Jung, Hyunsu Yeoh, Jang-il Kim, Jung Whan Chun, Han-Byoel Lee, Hyeong-Gon Moon, Wonshik Han. Longitudinal Changes of Contralateral Breast Mammographic Artificial Intelligence Algorithms Score in Ductal Carcinoma In Situ patient with Tamoxifen [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-04-11.
Abstract P3-05-46: scRNA-seq profiling reveals different tumor immune-microenvironment in triple negative breast cancer and decodes pivotal role of THBS1- SDC1 axis in tumor metastasis
Authors: Zhang Liyi , Zhang Qi , Li Pei , Xiong Min , Zhou Yue , Xue Jingyan , Chen Ming , Chi Wei-Ru , Ren Hengyu , Goh Chih Wan , Liu Douwaner , Wangxu Liren , Chi Yayun , Xiu Bingqiu , Wu Jiong 
Published: March 2023

Abstract
ABSTRACT Background: Breast cancer has become the most common cancer worldwide and triple-negative breast cancer (TNBC) is the most aggressive subtype due to the lacks of hormone receptors and HER2 expression. Increasing rate of breast cancer metastasis also need to be solved. Nearly one in four breast cancer patients developed metastasis after treatment, which attributed to 90% cancer related death. Considering highly aggressive pattern of TNBC, TNBC showed higher metastasis probability rather than other subtypes. Therefore, exploring more biomarkers and therapeutic targets are on urgent. Methods: We profiled the transcriptomes of 59646 cells from 12 primary and 4 metastatic tumor samples from Gene Expression Omnibus (GEO) database (https://www.ncbi.nlm.nih.gov/geo/). Results: Comparing with primary site, metastatic site was predominated with immunosuppressive tumor microenvironment. In brief, metastatic samples showed increasing numbers of macrophages, lower anti-tumor microenvironment scores, higher malignant cell properties scores, less effective T cells and macrophages, enhanced immune escape potential tumor cells and a later pseudotime state of malignant cells, compared with primary samples. Remarkably, metastatic samples exhibited a stronger interaction of THBS1-SDC1 axis between macrophage subcluster named angiogenesis-1 and malignant cell subcluster named CDKN2A epithelial cells. We subsequently confirmed that higher THBS1-SDC1 expression indicated with poor overall survival and distant metastatic free survival of TNBC patients in The Cancer Genome Atlas (TCGA) TNBC cohort. Conclusion: Our immune landscape of TNBC ecosystem provide deeper insights into tumor metastasis and offer potential biomarkers and therapeutic target for TNBC. Key words: Breast cancer; immune-microenvironment; THBS1; SDC1; metastasis
Citation Format: Liyi Zhang, Qi Zhang, Pei Li, Min Xiong, Yue Zhou, Jingyan Xue, Ming Chen, Wei-Ru Chi, Hengyu Ren, Chih Wan Goh, Douwaner Liu, Liren Wangxu, Yayun Chi, Bingqiu Xiu, Jiong Wu. scRNA-seq profiling reveals different tumor immune-microenvironment in triple negative breast cancer and decodes pivotal role of THBS1- SDC1 axis in tumor metastasis [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-05-46.