bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P1-03-10: Establishment and characterization of paired palbociclib-sensitive and resistant luminal A breast PDX models
Authors: Gamez Lizette , Moriarty Alyssa , Mashimo Tomoyuki , Papadopoulos Kyriakos , Rasco Drew , Patnaik Amita , Wick Michael J 
Published: March 2020

Abstract
Background: Palbociclib is one of three CDK 4/6 inhibitors approved in combination with an aromatase inhibitor for treatment of hormone receptor-positive breast cancer. Although this combination therapy has been found effective in some patients, resistance often develops. To aid in developing new therapies for CDK4/6-resistant breast cancer and better understand resistance mechanisms, we established a PDX model, designated ST1799, from a patient with luminal A breast cancer which was responsive to palbociclib in vivo and then conditioned the model with chronic drug administration until resistant. The resistant model, designated ST1799/PBR, and the parent were characterized for receptor expression, genomic alterations and in vivo drug sensitivity. Methods: ST1799 was established from an axillary lymph node FNA taken from a 66-year-old woman pretreated with various chemo and hormone therapies. The resulting model was passaged and a cohort challenged with chronic palbociclib treatment to produce drug resistance. The parent ST1799 and resistant ST1799/PBR were subjected to various comparative analyses including receptor expression, NGS and RNAseq and response to various relevant therapies. Results: Both models retained high ER staining (3+) expression and demonstrated comparable histopathology. DNA-based analysis of the parent model confirmed variants concordant with clinical mutation analysis. Comparison of the parent and resistant clone using RNAseq identified several alterations in variants and expression. In vivo palbociclib reported significant (p&lt;0.0001) activity towards ST1799 (T/C=11%) while ST1799/PBR was resistant towards the therapy (T/C=80%). Tamoxifen or fulvestrant treatment of ST1799 resulted in partial tumor regressions while activity in ST1799/PBR was less pronounced. Activity of abemaciclib or ribociclib was greater in ST1799/PBR compared with palbociclib treatment. Conclusion: We have established and characterized paired palbociclib-sensitive and resistant breast PDX models which can be utilized as valuable tools in better understanding CDK4/6i resistance and in developing new therapies for CDK4/6 inhibitor resistant patients.
Citation Format: Lizette Gamez, Alyssa Moriarty, Tomoyuki Mashimo, Kyriakos Papadopoulos, Drew Rasco, Amita Patnaik, Michael J Wick. Establishment and characterization of paired palbociclib-sensitive and resistant luminal A breast PDX models [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-03-10.
Abstract P1-04-01: Breast cancer patient derived scaffolds as a platform for studying cancer promoting properties of the microenvironment
Authors: Garre Elena , Gustafsson Anna , del Carmen Leiva-Arrabal Maria , Fitzpatrick Paul , Gregersson Pernilla , Ståhlberg Anders , Landberg Göran 
Published: March 2020

Abstract
Despite great efficiencies of today’s anti-cancer therapies in breast cancer medicine, recurrences and metastasis still remains a major challenge. The tumor initiating population of cancer stem cells (CSC) is believed to promote metastasis and drug resistance, suggesting that selectively targeting CSC and their niche may be a potential beneficial therapeutic strategy. However, specific driving factors in the microenvironment influencing the CSC niche remains unknown. To study the influence of specific cancer microenvironments, we have developed a novel three-dimensional cell culture platform, using cell-free patient derived scaffolds (PDS) from decellularized breast cancer tumors. We confirmed that our novel patient derived scaffold (PDS) recapitulates the native microenvironment where the cancer cells originate and, retains their biological properties. Our data demonstrate that culturing breast cancer cell lines in PDSs promotes CSC and EMT-like properties and decreases proliferation, similarly to in vivo conditions. Additionally, global gene expression profiling revealed that PDS cultures exhibit transcriptional patterns more similar to patient derived xenografts than to traditional monolayer cultures. Moreover, we analyzed the expression of cells cultured in 108 PDSs made from breast cancer tumors with clinical follow-up data, using a gene panel representative of relevant breast cancer related processes. This revealed that expression changes of several EMT markers and other CSC related genes in the PDS cultured cancer cells were correlated to clinical parameters such as grade, lymph node metastasis, patient survival and disease recurrences. Altogether, our data shows that PDS can reveal unique additional information about the malignancy-inducing properties of specific tumor microenvironments, potentially provides a complementary diagnosis tool for breast cancer tumors in vitro, and is a promising platform for drug screening of anti-cancer therapies.
Citation Format: Elena Garre, Anna Gustafsson, Maria del Carmen Leiva-Arrabal, Paul Fitzpatrick, Pernilla Gregersson, Anders Ståhlberg, Göran Landberg. Breast cancer patient derived scaffolds as a platform for studying cancer promoting properties of the microenvironment [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-04-01.
Abstract P1-04-02: Multicellular spheroids to dissect the interplay between human immune system and cancer
Authors: Ahmadzadeh Elaheh , Martinek Jan , Marches Florentina , Aucello Gabby , Yu Chun I , Palucka Karolina 
Published: March 2020

Abstract
The interaction between various components in the tumor environment plays a pivotal role in tumor development, migration and metastasis. While the 2-dimensional (2D) in vitro culture methods fail to assimilate the complexity of tumor microenvironment, the 3D multicellular tumor spheroids support co-culture conditions and allow a more physiologically relevant environment. We are working to establish such 3D model to investigate the molecular mechanisms regulating the interactions between human cancer cells such as melanoma or breast cancer, myeloid cells and T cells. Spheroids were developed using hanging drop technique with multiple cancer cell lines, dermal fibroblasts and immune cells. Preliminary experiments were carried out to determine the optimum conditions for spheroid formation. Spheroid formation occurred within 72 hours and their integrity was maintained throughout the experiments. Immunofluorescence analysis of spheroid cryosections showed a homogeneous distribution of fibroblasts in spheroids. Addition of purified blood CD14+ blood monocytes to the mixture of cancer cells and dermal fibroblasts enabled monocyte integration into spheroids. Adding melanoma specific CD8+ T cells to tumor spheroids formed by melanoma cell line (Me275), dermal fibroblasts and monocytes resulted in homogeneous infiltration and increased number of cell death. Addition of PBMCs to the mix of breast cancer cells and fibroblasts enabled the discrimination of spheroids into two groups, tumor spheroids with immune cells at the margin preferentially located at tumor margin and tumor spheroids with infiltrating immune cells. These preliminary observations resemble those from our in vivo models of humanized mice, where different tumor xenografts show different level of immune cell infiltration. Thus, our 3D model might allow the classification of tumor cells based on immune cell infiltration and could potentially be used to assess the distribution of immune infiltrates and the interaction of cancer cells with immune compartments.
Citation Format: Elaheh Ahmadzadeh, Jan Martinek, Florentina Marches, Gabby Aucello, Chun I Yu, Karolina Palucka. Multicellular spheroids to dissect the interplay between human immune system and cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-04-02.
Abstract P1-05-04: miR551b-3p promotes Oncostatin M signaling in breast cancer
Authors: Geethadevi Anjali , Parashar Deepak , Aure Miriam Ragle , George Jasmine , Chen Changliang , Mishra Jyotsna , Tahiri Andliena , Nair Bindu , Camara Amadou , Kristensen Vessela N , Pradeep Sunila , Raghavan Pradeep Chaluvally 
Published: March 2020

Abstract
An increased expression of oncogenic microRNA miR551b-3p (also known as miR551b) occurs in a subset of breast cancer due to genomic amplification of 3q26.2 locus. Using in silico and clinical sample analysis of breast cancer patient datasets, we identified that those breast cancer samples that encompass miR551b amplification express high levels of STAT3 mRNA and Oncostatin (OSM) family genes in triple-negative breast cancer (TNBC). Furthermore, high expression of Oncostatin family genes associates with poor outcome in estrogen receptor- negative breast cancer patients. In this study, we identified a previously unexplored mechanism that miR551b-3p promotes breast cancer progression and tumor growth by direct interaction of miR551b-3p with STAT3 promoter thereby activating STAT3 transcription. As a consequence, STAT3 upregulates a cytokine Oncostatin and its receptor Oncostatin M receptor (OSMR) and their interaction further induces STAT3 phosphorylation and an autocrine self-reinforcing loop in TNBC cells. In this study, we demonstrate that overexpression of miR551b-3p promoted proliferation, invasion and migration, epithelial to mesenchymal transition (EMT) and spheroid formation of breast cancer cells and its inhibition decreased the expression of miR551b-3p by inhibiting OSM, OSMR, IL6ST, IL31RA, phosphorylated and total STAT3 in breast cancer cells and reduced tumor cell growth. Overall, our results provide the first evidence that miR551b regulates OSM family gene expression by activating STAT3 and thereby promoting tumor cell growth and metastasis in breast cancer cells. Therefore, targeting miR-551b-3p-STAT3-OSMR axis and inhibiting their levels will provide an unprecedented therapeutic opportunity in breast cancer.
Citation Format: Anjali Geethadevi, Deepak Parashar, Miriam Ragle Aure, Jasmine George, Changliang Chen, Jyotsna Mishra, Andliena Tahiri, Bindu Nair, Amadou Camara, Vessela N Kristensen, Sunila Pradeep, Pradeep Chaluvally Raghavan. miR551b-3p promotes Oncostatin M signaling in breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-05-04.
Abstract P1-05-06: Functional characterization of lncRNA152 in ER+ and triple-negative breast cancers
Authors: Kim Daeseok 
Published: March 2020

Abstract
Genomic analyses have revealed that many RNA species other than protein-coding mRNAs are transcribed from mammalian genomes and may have profound effects on cellular physiology and pathology. One such class of RNAs are the long noncoding RNAs (lncRNAs). In our previous work using Global Run-On and sequencing (GRO-seq), we identified and annotated ~1,900 lncRNAs in MCF-7 human breast cancer cells, which are differentially expressed across the distinct molecular subtypes of breast cancer. Further meta-analysis identified lncRNA152 as a predictor of increased metastasis-free survival. Thus, lncRNA152 levels may serve as a biomarker to track disease progression in breast cancer patients. However, the precise mechanisms by which lncRNA152 regulates these clinical outcomes remain largely unknown. Interestingly, lncRNA152 is highly expressed in the luminal subtypes of breast cancer, but downregulated in triple-negative breast cancers (TNBC), suggesting that lncRNA152 expression may be associated with more aggressive cancer features. Through multiple complementary experimental approaches, we found that (1) FoxA1 regulates lncRNA152 transcription, (2) knockdown of lncRNA152 inhibits the growth, but promotes cell migration and invasion, of luminal breast cancer cell subtypes, and (3) ectopic overexpression of lncRNA152 inhibits TNBC cell growth, migration, and invasion. Importantly, our xenograft studies provide evidence that lncRNA152 inhibits estrogen-dependent tumor growth of luminal and TNBC cells. In addition, transcriptome analysis of TNBC cell-derived xenografts indicates that lncRNA152 expression downregulates many genes that are involved in biological processes such as cell growth, migration, invasion, and angiogenesis. Collectively, these results suggest that lncRNA152 is a novel tumor suppressor in luminal and basal subtype of breast cancer.
This work is supported by grants from the Cancer Prevention and Research Institute of Texas (CPRIT RP160318/RP190235) to W.L.K.
Citation Format: Daeseok Kim. Functional characterization of lncRNA152 in ER+ and triple-negative breast cancers [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-05-06.
Abstract P1-05-11: Breaking “vicious cycle”? The role of miR-223 in breast cancer metastasis to bone
Authors: Shan Zhen , Li Wen , Lin Ying , Zeng Huijuan , Qi Yunling , Lin Zefei , Fan Yuanjian 
Published: March 2020

Abstract
The “seed and soil” theory of metastasis was proposed by Stephen Paget in 1889. The theory suggests that bone acts as a fertile environment (soil) for cancer cells (seeds) colonization and growth. The theory successfully explains how bone and breast cancer cells interact to support breast cancer cell growth within the bone microenvironment.Breast cancer cells that metastasize to bone secrete growth factors and cytokines into the bone microenvironment that promote the production of receptor activator nuclear factor κ β ligand (RANKL), which, in turn, leads to osteoclast formation. The osteoclasts then cause bone resorption and the subsequent release of growth factors, include transforming growth factor-beta (TGF-β), bone morphogenetic proteins (BMPs), insulin-like growth factors (IGFs), fibroblast growth factors (FGFs), and platelet-derived growth factors (PDGF) into the bone microenvironment, which further stimulate the growth of breast cancer cells. Growth factors and cytokines produced by both breast cancer cells and bone cells result in a “vicious cycle” of bone breakdown: factors released from the bone promote breast cancer cell proliferation, which leads to more bone loss, and the subsequent release of more growth factors from the bone. The concept of the “vicious cycle” was proposed in 1997 by Mundy and Guise. Currently, the “vicious cycle” model provides the best description of our understanding of the interaction between breast cancer and bone. We found in miR-223 knockout mice, the bone volume of lowe limb bones is significantly lower than C57BL/6 mice (wild type), the osteoclastic resorption is more severe in miR-223 knockout mice according to H&E sections. Then, we hypothesized miR-223 may inhibit osteoclast formation. In vitro study, We found miR-223 can suppress RANKL activating osteocalst formation by targeting NF1A protein. These results indicated miR-223 may disturb the establishment of osteolytic lesion, which may destroy the “soil” in bone microenvironment. Besides, we also found in miR-223 knockout mice, the IGF-1R is over expressed and the PI3K-Akt pathway was excessively activated. miR-223 up-regulation can inhibit MDA-231 cell proliferation but enhance apoptosis, which may destroy the “seed” in bone microenvironment. In conclusion, we hypothesized that miR-223 may break the “vicious cycle” and suppress breast cancer metastasis to bone.
Citation Format: Zhen Shan, Wen Li, Ying Lin, Huijuan Zeng, Yunling Qi, Zefei Lin, Yuanjian Fan. Breaking “vicious cycle”? The role of miR-223 in breast cancer metastasis to bone [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-05-11.
Abstract P1-10-21: PD-L1 expression of tumor infiltrating immune cells has potential as a biomarker in triple-negative breast cancers
Authors: Harada Yurina , Kubo Makoto , Mori Hitomi , Kai Masaya , Yamada Mai , Kurata Kanako , Kawaji Hitomi , Kaneshiro Kazuhisa , Hayashi Saori , Shimazaki Akiko , Morisaki Takafumi , Yamaguchi Rin , Arima Nobuyuki , Nishimura Reiki , Okido Masayuki , Nakamura Masafumi 
Published: March 2020

Abstract
[background] In general, TNBC has a high distant metastasis rate and is highly aggressive. Despite good response to chemotherapy, it has a poorer prognosis compared to other subtypes. There is a need to develop new treatments for the selection of appropriate treatments. At present, treatments using an immune check point blockade are attracting attention, and the evaluations as biomarkers of and, PD-1 / PD-L1 expression on immune cells for therapeutic effects and prognosis in TNBC are controversial. In order to select patients with TNBC for who immunotherapy is likely to be effective, new biomarkers need to be explored.
[Purpose] Our aim is to investigate the possibility as a biomarker of PD-L1 expression on immune cells(PD-L1/IC) in TNBC. We also assess the relationship among PD-L1/IC, PD-L1 expression on tumor cells(PD-L1/TC) and TIL.
[Methods] This study included 248 patients with primary TNBC who underwent resection without neoadjuvant chemotherapy at Kyushu University Hospital(Fukuoka, Japan) and related hospitals between January 2004 and December 2014.
[Results] PD-L1/IC was positive in 129 cases (52.0%) of 248 TNBCs. Although there was no significant difference in RFS and OS between the positive and negative groups, PD-L1/IC-positive and TIL-High group showed the best prognosis, considering the combination whether PD-L1/IC was positive or negative, and TIL was high or low. PD-L1/IC was significantly correlated with PD-L1/TC(p&lt;0.001). In addition, there was a significant correlation between TIL rate and PD-L1/IC(p&lt;0.001). Moreover, PD-L1/IC-positive group showed stronger therapeutic effects of anthracycline both in OS and RFS, compared with the PD-L1/IC-negative group.
[Conclusion] In TNBC, the relationship between PD-L1/IC and prognosis is still not clear, but in IMpassion130 trial, PD-L1/IC is a predictive marker for the effect of Atezolizumab. PD-L1/IC has potential as an immune biomarker in TNBCs. This study also found that PD-L1/IC was related to the therapeutic effect of anthracycline. PD-L1/IC may be a predictive marker of the efficacy of various treatments.
Citation Format: Yurina Harada, Makoto Kubo, Hitomi Mori, Masaya Kai, Mai Yamada, Kanako Kurata, Hitomi Kawaji, Kazuhisa Kaneshiro, Saori Hayashi, Akiko Shimazaki, Takafumi Morisaki, Rin Yamaguchi, Nobuyuki Arima, Reiki Nishimura, Masayuki Okido, Masafumi Nakamura. PD-L1 expression of tumor infiltrating immune cells has potential as a biomarker in triple-negative breast cancers [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-10-21.
Abstract P1-15-08: Real world data on treatment patterns before and after reporting of the KATHERINE trial: A phase 3 study of adjuvant Ado-trastuzumab emtansine (TDM1) versus trastuzumab in early stage HER+ breast cancer
Authors: Margolis Neil , Kozlovsky Vlad , Flood William , Reddy Sandeep 
Published: March 2020

Abstract
BACKGROUND: At SABCS 2018 and simultaneous publication in the NEJM, results of the phase 3 KATHERINE clinical trial comparing TDM1 vs trastuzumab as adjuvant therapy in patients with HER2-positive early-stage breast cancer with residual invasive disease after receiving neoadjuvant chemotherapy and trastuzumab, showed that TDM1 reduced the risk of invasive recurrence or death by 50%. We sought to determine the effect of the release of this data on clinical practice of general medical oncologists in the US by comparing the requests for treatment authorization for TDM1 in the quarters preceding and following SABCS 2018. METHODS: data from a pre-authorization platform used by multiple commercial insurance companies in the US (Eviti) was analyzed. Analysis for request for use of TDM1 was limited to 2nd and 3rd line of therapy in patients with a diagnosis of HER2+ breast cancer in stage &lt;4 patients. Between 1/1/2018 and 6/30/2019, 29,525 breast cancer treatment plans were identified, of which 7,969 were identified as HER2-NEU+ (27%), either IHC3+ or FISH+. TDM1 was prescribed at any line of therapy in 886 patients (11%). RESULTS: Before April 5th 2019, when the adjuvant TDM1 regimen was published, users who entered the drug would have to pick one of the other 2 TDM1 regimens (1st line or 2nd line+). They could change the line of therapy to adjuvant if appropriate. TDM1 authorizations are shown in TABLE 1, indicating an immediate increase in TDM1 use in the quarter following SABCS and based on the quarter 2, 2019 data showing a 42% adjuvant-use rate, we model that 99 cases would have received adjuvant TDM1 in Q1 2019 after 0 in Q4 2018.
Q 1, 2018Q 2, 2018Q 3, 2018Q 4, 2018Q 1, 2019Q 2, 2019TDM1 Adjuvant097TDM1 First Line11178195925TDM1 Second Line+104939276177108
CONCLUSIONS: Clinical uptake of practice changing data presented at SABCS 2018 regarding TDM1 was relatively rapid. SABCS and rapid simultaneous publication serves as an important and effective mechanism to communicate practice changing clinical data to practicing oncologists in the US.
Citation Format: Neil Margolis, Vlad Kozlovsky, William Flood, Sandeep Reddy. Real world data on treatment patterns before and after reporting of the KATHERINE trial: A phase 3 study of adjuvant Ado-trastuzumab emtansine (TDM1) versus trastuzumab in early stage HER+ breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-15-08.