bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P2-06-03: Dietary exposure to acrylamide and breast cancer risk: results from the NutriNet-Santé cohort
Authors: Bellicha Alice , Wendeu-Foyet Gaëlle , Coumoul Xavier , Koual Meriem , Pierre Fabrice , Guéraud Françoise , Zelek Laurent , Debras Charlotte , Srour Bernard , Sellem Laury , Kesse-Guyot Emmanuelle , Julia Chantal , Galan Pilar , Hercberg Serge , Deschasaux-Tanguy Mélanie , Touvier Mathilde 
Published: March 2023

Abstract
Background: Acrylamide is classified as a probable human carcinogen by the IARC but epidemiological evidence on the carcinogenicity of acrylamide from dietary sources is limited. This study aimed to investigate the associations between dietary acrylamide and breast cancer risk in the NutriNet-Santé cohort. Methods: This prospective cohort study included 80,597 French women (mean [SD] age at baseline: 40.8 [14] years) during a mean (SD) follow-up of 8.8 (2.3) years. Acrylamide intake was evaluated using repeated 24h dietary records (n= 5.5 [SD 3.0]), linked to a comprehensive food composition database. Associations between acrylamide intake and breast cancer risk (overall, premenopausal and post-menopausal) were assessed by Cox hazard models adjusted for known risk factors. Results: The mean (SD) dietary acrylamide intake was 30.1 (21.9) µg/d (main contributors: coffee, potato fries and chips, pastries and cakes, and bread). During follow-up, 1016 first incident breast cancer cases were diagnosed (431 premenopausal, 585 postmenopausal). A borderline significant positive association was observed between acrylamide intake and breast cancer risk overall (HRQ4 vs Q1= 1.21 [95% CI: 1.00-1.47]) and a positive association was observed with premenopausal cancer (HRQ4 vs Q1= 1.40 [95% CI: 1.04-1.88]). Restricted cubic spline analyses suggested evidence for non-linearity of these associations, with higher HR for intermediate (Q2) and high (Q4) exposures. Receptor-specific analyses revealed a positive association with estrogen receptor-positive breast cancer, which represented 86% of total cancer cases. Acrylamide intake was not associated with post-menopausal breast cancer. Conclusions: Results from this large prospective cohort study suggest the potential deleterious role of dietary acrylamide in breast cancer etiology, especially in premenopausal women, and provide new insights that should encourage further mitigation strategies to reduce the content of acrylamide in food.
Citation Format: Alice Bellicha, Gaëlle Wendeu-Foyet, Xavier Coumoul, Meriem Koual, Fabrice Pierre, Françoise Guéraud, Laurent Zelek, Charlotte Debras, Bernard Srour, Laury Sellem, Emmanuelle Kesse-Guyot, Chantal Julia, Pilar Galan, Serge Hercberg, Mélanie Deschasaux-Tanguy, Mathilde Touvier. Dietary exposure to acrylamide and breast cancer risk: results from the NutriNet-Santé cohort [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 P2-06-03.
Abstract P2-21-06: The relationship between the gene expression difference of fibroblasts in the tumor microenvironment and metastasis of triple-negative breast cancer
Authors: Heo Woo Hang , Lee Woochan , LI SONGBIN , Kim Jong-Il , Moon Hyeong-Gon 
Published: March 2023

Abstract
Background Triple negative breast cancer (TNBC) is a breast cancer subtype with increased risk of distant metastasis, especially to lung and liver. In addition to the intrinsic characteristics of tumor cells, the molecular features of the tumor microenvironment cells can also regulate the metastasis process of TNBC. In this study, we tried to characterize the transcriptomic features of microenvironment fibroblasts associated with the distant metastasis of TNBC. Method We established PDX models by obtaining tumor tissues from 26 triple-negative breast cancer patients and transplanting them into the mammary fat pads of immunodeficient mice. When the PDX tumors grew sufficiently in the fat pads, we excised them and saved the mice to assess whether each PDX tumor was capable of developing spontaneous distant metastasis. We used bulk RNA sequencing and single cell RNA sequencing to determine the transcriptomic features associated with the distant metastasis. Results We classified the 26 TNBC PDX models based on their in vivo metastasis capacity and the clinical outcomes of the corresponding patients. Non-metastatic PDX models were defined as the lack of developing distant metastasis in either mouse experiment or clinical follow-up data (n=5). PDX models were defined as metastatic models when they developed distant metastasis in both mouse and human (n=4). We performed single cell RNA sequencing using the nine PDX tumors and observed a substantial gene expression differences of fibroblasts in the tumor microenvironment between the metastatic and non-metastatic PDX models. The fibroblasts of the metastatic PDX models showed up-regulation of genes involved in the response to hypoxia, inflammatory response, neutrophil chemotaxis, cellular response to IL-1, positive regulation of cell proliferation, and negative regulation of apoptotic process. Moreover, this difference of gene expression between metastatic and non-metastatic TNBC PDX models were not identified by the bulk RNA sequencing data. Conclusion By using the single cell RNA sequencing using the TNBC PDX models, we identified key features of fibroblasts in the tumor microenvironment that contributes to the metastasis capacity of TNBC. Further studies are on-going to elucidate the underlying mechanisms.
Citation Format: Woo Hang Heo, Woochan Lee, SONGBIN LI, Jong-Il Kim, Hyeong-Gon Moon. The relationship between the gene expression difference of fibroblasts in the tumor microenvironment and metastasis of 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 P2-21-06.
Abstract P2-26-03: TRAF3 as a regulator of breast cancer aggressiveness
Authors: Papanastasiou Anastasios , Sirinian Chaido , Theakou Maria , Peroukidis Stavros , Chaniotis Dimitrios , Kalofonos Haralabos , Koutras Angelos 
Published: March 2023

Abstract
TRAF3 (TNF Receptor Associated Factor 3) is a regulator of NF-κB signaling, acting mainly as an inhibitor of the alternative NF-κB pathway through the interaction with other TRAF molecules and the downregulation of NIK (MAP3K14) kinase. While NF-κB has a well-established role in breast cancer development and progression, TRAF3 which acts as a ubiquitin-ligase in the NF-κB cascade has never been studied in mammary carcinomas. Here by employing breast cancer cell lines in invasion and colony formation assays, we show that TRAF3 forced expression inhibits aggressive traits of breast cancer cells. In addition, immunohistochemistry (IHC) for TRAF3 protein in breast cancer FFPE samples and analysis of TRAF3 gene expression from publicly available data sets, indicates that TRAF3 mRNA and protein expression in breast cancer tissue correlates with Recurrence Free Survival (RFS), Overall Survival (OS) and other clinicopathological parameters such as Histological Grade and proliferation index (ki-67). To our knowledge this is the first report on TRAF3 protein in breast cancer providing preliminary evidence for an inhibitory role of this protein in breast cancer development and progression.
Citation Format: Anastasios Papanastasiou, Chaido Sirinian, Maria Theakou, Stavros Peroukidis, Dimitrios Chaniotis, Haralabos Kalofonos, Angelos Koutras. TRAF3 as a regulator of breast cancer aggressiveness [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 P2-26-03.
Abstract P2-26-04: Human papillomavirus protein E6 regulates Toll like receptor-9 expression in breast cancer cells
Authors: Parviainen Essi , Nurmenniemi Sini , Bravaccini Sara , Pirini Francesca , Ravaioli Sara , Jukkola Arja , Selander Katri S. 
Published: March 2023

Abstract
Toll like receptor-9 (TLR9) is an innate immunity DNA-receptor, which is widely expressed in various cancers, including breast cancer. Low TLR9 expression in cancer cells was initially associated with poor prognosis among patients with triple negative breast cancer. We have now discovered a similar association also among among other breast cancer subtypes. The mechanism for TLR9-associated poor prognosis is not currently known, but our ongoing studies suggest that it may be due to poor chemotherapy responses. Regulation of TLR9 expression in breast cancer is poorly understood. It has been demonstrated that in cervical cancers, TLR9 expression is suppressed by human papillomavirus (HPV) infections. Although breast cancer is not typically considered HPV-associated, there are reports of HPV in breast cancer. The aim here was to test the hypothesis, that HPV-infections suppress TLR9 expression also in breast cancer. To study this, human breast cancer cells were infected with HPV16 E6-oncoprotein, followed by measurement of TLR9 mRNA and protein in vitro. We also aimed to compare the presence of HPV DNA with TLR9 protein expression in clinical breast cancer specimens. We further studied E6-infection effects on breast cancer proliferation, migration, and invasion. E6-infection decreased TLR9 protein expression in TNBC but not in estrogen receptor expressing (ER+) cells. E6-overexpression significantly altered breast cancer proliferation, but the impact was opposite in TNBC and ER+ cells. No effect on migration and invasion was observed. E6-transfected breast cancer cells were significantly less sensitive in vitro to chemotherapies typically used for the treatment of breast cancer in the adjuvant setting. In vivo studies are pending. HPV DNA was not detected in a pilot cohort of clinical breast cancer specimens (n=37) among Northern Finnish breast cancer specimens. These results indicate that HPV may affect breast cancer TLR9 expression and thereby breast cancer prognosis, through treatment responses. Although HPV was not detected in the small pilot set of our clinical samples, this issue needs to be further studied in larger data sets.
Citation Format: Essi Parviainen, Sini Nurmenniemi, Sara Bravaccini, Francesca Pirini, Sara Ravaioli, Arja Jukkola, Katri S. Selander. Human papillomavirus protein E6 regulates Toll like receptor-9 expression in breast cancer cells [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 P2-26-04.
Abstract P2-26-14: CDK4/6 inhibitors modulate the ubiquitin–proteasome pathway in ER+ breast cancer by downregulation of UBE2C/S/T
Authors: Lin Chih-Yi , Yu Chung-Jen , Liu Chun-Yu , Chao Ta-Chung , Huang Chi-Cheng , Tseng Ling-Ming , Lai Jiun-I 
Published: March 2023

Abstract
Despite significant improvement in therapeutic development in the past decades, breast cancer remains a formidable cause of death for women worldwide. The hormone positive subtype (HR(+)) (also known as luminal type) is the most prevalant category of breast cancer, comprising ~70% of patients. The clinical success of the three CDK4/6 inhibitors palbociclib, ribociclib, and abemaciclib has revolutionized the treatment of choice for metastatic HR(+) breast cancer. Accumulating evidence demonstrate that the properties of CDK4/6 inhibitors extend beyond inhibition of the cell cycle, including modulation of immune function, sensitizing PI3K inhibitors, metabolism reprogramming, kinome rewiring, modulation of the proteosome, and many others. The ubiquitin–proteasome pathway (UPP) is a crucial cellular proteolytic system that maintains the homeostasis and turnover of proteins. By transcriptional profiling of the HR(+) breast cancer cell lines MCF7 and T47D treated with Palbociclib, we have uncovered a novel mechanism that demonstrate the CDK4/6 inhibitors suppress the expression of three ubiquitin conjugating enzymes UBE2C, UBE2S, UBE2T. Further validation in the HR(+) cell lines show that Palbociclib and ribociclib decrease UBE2C at both the mRNA and protein level, but this phenomenon was not shared with abemaciclib. These three E2 enzymes modulate several E3 ubiquitin ligases, including the APC/C complex which plays a role in G1/S progression. We further demonstrate the UBE2C/UBE2T expression levels are associated with breast cancer survival, and HR(+) breast cancer cells demonstrate dependence on the UBE2C. Our study suggests a novel link between CDK4/6 inhibitor and UPP pathway, adding to the potential mechanisms of their clinical efficacy in cancer.
Citation Format: Chih-Yi Lin, Chung-Jen Yu, Chun-Yu Liu, Ta-Chung Chao, Chi-Cheng Huang, Ling-Ming Tseng, Jiun-I Lai. CDK4/6 inhibitors modulate the ubiquitin–proteasome pathway in ER+ breast cancer by downregulation of UBE2C/S/T [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 P2-26-14.
Abstract P3-05-49: Number of involved organs at baseline is prognostic for overall survival in patients with metastatic breast cancer: Results from the AGMT_MBC-Registry
Authors: Rinnerthaler Gabriel , Gampenrieder Simon P. , Tinchon Christoph , Petzer Andreas , Balic Marija , Heibl Sonja , Sandholzer Margit , Zabernigg August F. , Egle Daniel , Hager Christopher , Pichler Petra , Roitner Florian , Andel Johannes , Strasser-Weippl Kathrin , Knauer Michael , Hubalek Michael , Singer Christian F. , Greil Richard 
Published: March 2023

Abstract
Background: Hormone-receptor (HR) status, HER2 Status, de novo metastatic disease, distant recurrence-free interval (DRFI), and visceral disease are known prognostic factors in metastatic breast cancer (MBC). Therefore, in the majority of clinical trials, randomization is stratified for these parameters. Whether the number of involved organs at baseline has an additional prognostic value was examined in this analysis.
Patients and methods: The AGMT-MBC-Registry is a multicenter nationwide ongoing retrospective and prospective registry for MBC patients in Austria. In this analysis, patients with known HR status, HER2 status, and available survival data were included. Multivariable hazard ratios were estimated by COX proportional hazard models. For variable selection a backward stepwise model selection using the Akaike information criterion was performed.
Results: As of 04/05/2022, 2,235 patients have been included in the registry, of which 1,840 patients fulfilled the inclusion criteria. In two different multivariable COX proportional hazard models for overall survival, the number of involved organs was a highly statistically significant independent prognostic factor: (1) a model including the number of involved organs at baseline together with known prognostic factors (see Table 1); (2) a stepwise selection model additionally including menopausal status and involved metastatic organ sites (bone, liver, lung, brain, and lymph nodes) separately. This effect was maintained in sensitivity analysis taking different breast cancer subtypes as well as visceral and non-visceral disease into account.
Conclusion: The number of involved organs at baseline is an independent prognostic factor in MBC and should be considered as a stratification factor in randomized trials.
Table 1. Multivariable Model for overall survival.
Citation Format: Gabriel Rinnerthaler, Simon P. Gampenrieder, Christoph Tinchon, Andreas Petzer, Marija Balic, Sonja Heibl, Margit Sandholzer, August F. Zabernigg, Daniel Egle, Christopher Hager, Petra Pichler, Florian Roitner, Johannes Andel, Kathrin Strasser-Weippl, Michael Knauer, Michael Hubalek, Christian F. Singer, Richard Greil. Number of involved organs at baseline is prognostic for overall survival in patients with metastatic breast cancer: Results from the AGMT_MBC-Registry [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 P3-05-49.
Abstract P4-03-44: A Case Series of Male Breast Cancer Patients at Methodist Dallas Medical Center
Authors: Nong Huy , Moparty Vasu , Manhas Atisha 
Published: March 2023

Abstract
Male breast cancer is a rare disease accounting for less than 1% of all breast cancer diagnosis. Male breast cancers occur later in life and are more estrogen receptor-positive compared to female breast cancers. Breast cancer in men is often diagnosed later and survival rates are lower than in female cases. The aim of this retrospective study is to analyze the epidemiological, clinical and therapeutic data of all male breast cancer cases over the span of 11 years to at Methodist Dallas Medical Center between 2010 – 2021. During this time period, there was a total of 1,784 cases of breast cancer diagnosed. There were 8 cases male breast cancers, accounting for 0.45% of all breast cancer cases. The average age of diagnosis was 69.5 years old. The most common type of male breast cancer was invasive ductal carcinoma with 7 cases (87.7%). The remaining 1 case (12.5%) were ductal carcinoma in situ (DCIS). 100% of our male breast cancer cases were estrogen receptor and progesterone receptor positive. No male breast cancer case had Her2/Neu receptor over-expression. Of all male breast cancer cases, 75% had a family history of cancer suggesting that genetic factors play a significant role in the development of breast cancer in men. At time of diagnosis, 4 cases (50 %) were staged at cT4 and the remainder of cases were between cT0 - cT2. 37.5% of all cases had sentinel lymph node involvement at time of diagnosis. From the time period of 2010 – 2014 there were no incidences of male breast cancer; however, from 2015 – 2021 there were 8 total cases. There were 2 cases (25%) of death.
Number of Male Breast Cancer Cases by Year Number of Male Breast Cancer Cases by Year
Number of male breast cancer cases diagnosed by year at Methodist Dallas Medical Center
Epidemiological and Clinical Data of Male Breast Cancer Cases
Citation Format: Huy Nong, Vasu Moparty, Atisha Manhas. A Case Series of Male Breast Cancer Patients at Methodist Dallas Medical Center [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 P4-03-44.
Abstract P4-07-26: Development of CDCP1-targeting antibody-drug conjugate for Triple negative and metastatic breast cancer
Authors: Gough Madeline , Khan Tashbib , Kwah Kayden , He Yaowu , Ratnayake Gishan , Pyke Christopher , Snell Cameron , Hooper John , Kryza Thomas 
Published: March 2023

Abstract
Introduction: CUB-domain containing- protein 1 (CDCP1) is a transmembrane receptor involved in the progression of several cancers. Recent studies demonstrate that CDCP1 is a rational target for the development of innovative targeted therapies for cancer including theranostics agents and antibody-drug conjugates. Objective/Methods: To determine the therapeutic potential of CDCP1 in breast cancer, we investigated its expression in multiple cohorts of breast cancer tissues by immunohistochemistry, as well as in various preclinical models including cell lines, primary cells and patient-derived xenografts using flow cytometry, western blot and immunofluorescence staining. Then, we evaluated the capacity of the CDCP1-targeting chimeric antibody ch10D7 to specifically accumulate in breast cancer lesions in in vivo preclinical models including patient-derived xenografts and breast cancer metastasis models. Finally, we determined the efficacy of the ch10D7-MMAE antibody-drug conjugate to kill breast cancer cells in vitro and breast tumours ex-vivo and in vivo. Results: The CDCP1 receptor is expressed at targetable level in a significant proportion of breast cancer cases with high/intermediate expression detected in ~30% of localized ER-positive cases, ~50% of metastatic ER-positive cases and &gt;70% of Triple negative or HER2-positive cases. Similar proportion of expression was detected in cellular models. We demonstrated that ch10D7 antibody labelled with the radionucleotide Zircodium-89 specifically accumulates in breast cancer lesions in vivo allowing the detection of mammary-fat pad implanted patient-derived xenografts and of breast cancer metastasis by PET/CT imaging. Finally, we confirmed that the ch10D7-MMAE antibody-drug conjugate is very efficient at inducing cell death in vitro as well as controlling primary tumour and metastatic tumour burden in pre-clinical models, conferring a significant survival advantage compared to classical therapy. Conclusion: Our work demonstrates that CDCP1 is a potential target to detect and limit the progression of breast tumours and that biomolecules specifically recognising this receptor are promising agents which could improve survival of patients.
Citation Format: Madeline Gough, Tashbib Khan, Kayden Kwah, Yaowu He, Gishan Ratnayake, Christopher Pyke, Cameron Snell, John Hooper, Thomas Kryza. Development of CDCP1-targeting antibody-drug conjugate for Triple negative and metastatic 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 P4-07-26.