bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract OT1-01-04: A randomized phase 2 study of peri-operative ipilimumab, nivolumab and cryoablation versus standard care in women with residual, early stage/resectable, triple negative breast cancer after standard-of-care neoadjuvant chemotherapy
Authors: McArthur Heather , Comen Elizabeth , Bryce Yolanda , Solomon Stephen B , Leal Jorge , Rodine Micaela , Abaya Christina DiLauro , Patil Sujita , Page David , Norton Larry 
Published: March 2020

Abstract
Background: Local tumor destruction with cryoablation (cryo) induces inflammation and releases antigens that can activate tumor-specific immune responses. Pre-clinically, cryo with checkpoint inhibition augmented tumor-specific immune responses and prevented recurrence. Clinically, we established that peri-operative (peri-op) cryo with ipilimumab (ipi) +/- nivolumab (nivo) was not only safe in patients (pts) with operable, early stage breast cancer (ESBC) but also generated robust intra-tumoral and systemic immune responses. In this randomized phase 2 study, we evaluate the disease specific impact of peri-op ipi/nivo/cryo versus standard care in women with residual triple negative breast cancer (TNBC) after neoadjuvant chemotherapy (NAC), a subset at high risk of early relapse.
Methods: Eligible pts are ≥18y, with ER &lt;10%, PR &lt;10%, HER2 negative (per ASCO/CAP definition), ≥ 1.0 cm, residual operable disease after taxane-based NAC. Approximately 160 pts will be randomized to one of two arms: breast surgery (control arm) or ipi/nivo/cryo followed by breast surgery and adjuvant nivo (intervention arm). Pts in the intervention arm will undergo percutaneous, image-guided cryo with concurrent research core biopsy 7-10 days prior to surgery and will receive ipi (1mg/kg IV) with nivo (240mg IV) 1 to 5 days prior to cryo. After surgery, pts will receive 3 additional doses of nivo at 240mg IV Q2 weeks. Adjuvant capecitabine is recommended for all patients per local standard-of-care. Patients will be stratified by NAC platinum administration, NAC anthracycline administration, and clinical nodal status (positive versus negative). The primary endpoint is 3-year Event Free Survival (EFS). Secondary endpoints include Invasive Disease-Free Survival (IDFS), Distant Disease-Free Survival (DDFS), overall survival (OS) and safety. Exploratory correlative studies will be performed on tumor and serum to characterize the immunologic impact of the intervention and to explore predictors of efficacy and toxicity.
Citation Format: Heather McArthur, Elizabeth Comen, Yolanda Bryce, Stephen B Solomon, Jorge Leal, Micaela Rodine, Christina DiLauro Abaya, Sujita Patil, David Page, Larry Norton. A randomized phase 2 study of peri-operative ipilimumab, nivolumab and cryoablation versus standard care in women with residual, early stage/resectable, triple negative breast cancer after standard-of-care neoadjuvant chemotherapy [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 OT1-01-04.
Abstract OT1-01-05: AIPAC (Active Immunotherapy PAClitaxel): A randomized, double blind, placebo controlled, multinational phase IIb trial evaluating the efficacy of eftilagimod alpha (a soluble LAG-3 fusion protein) in combination with paclitaxel in hormone receptor positive metastatic breast cancer
Authors: Dirix Luc , Wildiers Hans , Huizing Manon T , De Cuypere Eveline , Schröder Carolina P , Armstrong Anne C , Huober Jans , Marmé Frederik , Schneeweiss Andreas , Khan Sarah , Triebel Fréderic 
Published: March 2020

Abstract
Background: Eftilagimod alpha (efti, previously IMP321) is a recombinant LAG-3Ig fusion protein that binds to MHC class II and mediates antigen-presenting cell (APC) activation followed by CD8 T-cell activation. Efti may lead to the activation of the dendritic cell network and to a strong anti-tumor CD8 T cell response when injected s.c. after chemotherapy at a time when these APC are loaded with tumor antigens. AIPAC (Active Immunotherapy PAClitaxel; NCT02614833) is a Phase IIb trial in hormone receptor (HR)-positive metastatic breast carcinoma patients receiving efti or placebo as adjunctive to weekly paclitaxel as a first-line chemotherapy. The randomized double blinded part (stage 2) has finished recruitment in June 2019. Primary analysis is expected Q1 2020.
Methods: This clinical trial is a placebo-controlled, double-blind, 1:1 randomized Phase IIb study aimed to enrol 226 patients at multiple centres across 7 different European countries. Patients with metastatic, HR-positive breast adenocarcinoma receiving first line chemotherapy with weekly paclitaxel and with measurable disease according to RECIST 1.1 are eligible. Patients suitable for Her2/neu targeted therapy are excluded from the trial. In the first treatment phase, paclitaxel (80 mg/m² IV at D1, D8, D15 plus efti (30 mg s.c.) or placebo at D2, D16 will be administered for 6 cycles (1 cycle = 4 weeks). This is followed by a maintenance phase in which stable or responding patients will receive efti or placebo for up to additional 52 weeks (12 injections). The primary endpoint is progression-free survival (PFS) by blinded independent central imaging review. Secondary endpoints include PFS by local assessment, overall survival, tumor response according to RECIST 1.1., time to and duration of response, duration of stable disease and quality of life.
Citation Format: Luc Dirix, Hans Wildiers, Manon T Huizing, Eveline De Cuypere, Carolina P Schröder, Anne C Armstrong, Jans Huober, Frederik Marmé, Andreas Schneeweiss, Sarah Khan, Fréderic Triebel. AIPAC (Active Immunotherapy PAClitaxel): A randomized, double blind, placebo controlled, multinational phase IIb trial evaluating the efficacy of eftilagimod alpha (a soluble LAG-3 fusion protein) in combination with paclitaxel in hormone receptor positive metastatic 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 OT1-01-05.
Abstract OT2-04-01: A prospective, multicentre, open-label, randomized phase II study of PEmbroLizumab in combination with neo-adjuvant (F)EC-paclitaxel regimen in HER2-negative Inflammatory breast CANcer
Authors: Gonçalves Anthony 
Published: March 2020

Abstract
Background: Inflammatory breast cancer (IBC) represents a rare but aggressive form of locally advanced BC. In spite of multimodality therapy including neoadjuvant chemotherapy (NAC), radical surgery and radiotherapy, prognosis remains poor, notably in HER2-negative subtypes. Whole-genome and gene expression profiling studies in IBC have identified an immune-enriched signature predicting for pathological complete response (pCR), suggesting a critical role for T-cell cytotoxicity in reaching complete tumor cell elimination after NAC. In addition, overexpression of programmed cell death ligand 1 (PD-L1) mRNA in IBC is more frequent than in non-IBC and has significant correlation with pCR. Pembrolizumab (PEM), an anti- programmed cell death 1 (PD 1) receptor antibody, inhibiting its interaction with PD-L1, is registered or in development across a large range of malignancies. PEM may boost anti-tumor immunity, eradicating residual tumor cells and thus improving pCR and outcome in HER2-negative IBC.
Trial design: PELICAN-IPC 2015-016 trial (NCT03515798), sponsored by Institut Paoli-Calmettes with financial support of MSD, is a multicenter, randomized phase II, non-comparative study evaluating the addition of PEM to anthracyclines/taxanes NAC in non-metastatic HER2-negative IBC. Patients will receive 4 cycles of Q3W FEC100 (5FU 500 mg/m², Epirubicin 100 mg/m², Cyclophosphamide 500 mg/m²; non-triple negative) or 4 cycles of Q2W EC (Epirubicin 90 mg/m², Cyclophosphamide 600 mg/m²; triple-negative) followed by Q1W paclitaxel 80 mg/m² x 12, with (arm B) or without (arm A) Q3W IV PEM 200 mg started with C2 FEC/EC. The primary endpoint will be pCR in the experimental arm. The study also includes a run-in safety phase. Secondary endpoints include tolerance, invasive disease-free, event-free and overall survivals in each arms and collection of pre- and post-treatment tissue and blood samples for pharmacodynamics measurements and biological correlates. Following Simon’s 2-stage optimal procedure a total of 54 patients in arm B is required to reject the null hypothesis of a truly ineffective experimental arm (H0: p&lt;= 20%) with 5% error risk and 90% power assuming a true pCR rate of 40%. 27 additional patients will be enrolled in the control arm A. Since June 2018, 7 patients have been enrolled in a single center and 13 additional centers are expected to open before the end of 2019.
Citation Format: Anthony Gonçalves. A prospective, multicentre, open-label, randomized phase II study of PEmbroLizumab in combination with neo-adjuvant (F)EC-paclitaxel regimen in HER2-negative Inflammatory 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 OT2-04-01.
Abstract OT3-14-01: GERA: A health economic trial to analyze the impact of ehealth in breast cancer care
Authors: Eggersmann Tanja , Riese Christoph , Wenzel Claudia , Schinkoethe Timo , Degenhardt Tom , Wuerstlein Rachel , Harbeck Nadia , Welslau Manfred 
Published: March 2020

Abstract
Background: In breast oncology, the increasing number of oral drug therapies pose great challenges for patient management. Numerous studies demonstrate that well-informed patients develop higher confidence in their treatment and a greater sense of disease control, resulting in increased adherence and persistence as well as potentially better outcome. Patients need knowledge, skills and confidence to actively participate in their own care. Moreover, such skills also contribute to reduction of planned and unplanned visits and of accompanying a time expenditure of the practice staff, thus lowering the costs of the whole treatment. Enhanced quality of life also affects financial resources by reducing sick leaves at work. The electronic Patient Reported Outcome (ePRO) tool CANKADO is designed to help oncologists to bridge the gap between good, personalized care and a time and resource-saving treatment for cancer patients. CANKADO helps patients and their physicians regarding therapy management by a standardized documentation procedure and, if needed, direct feedback to patients by the integrated Pro-React system. Methods: Aim of GERA is to assess the economic impact of an ePRO tool in breast cancer care. It is a prospective, single arm, non-interventional trial, based on questionnaires that answered by patients via the CANKADO Patient App. All patients undergoing systemic therapy for breast cancer with access to CANKADO will be included in the evaluation. This study will take place in 10 German centers and 337 patients will be included in the study. The enrollment phase of patients will last 6 months, while the individual patient observation and accompaniment phase through CANKADO will continue for 3 months. Primary objective is to gain knowledge on the health economic impact of CANKADO resource utilization in breast cancer care including the evaluation of physicians’ time and patient experience. As secondary objectives, exploratory analysis of all collected information is planned. This includes the socio-demographic patient information, clinical characteristics, quality-of life and patient documentation behavior. Results: The GERA trial is ongoing. Results will be presented at the conference. Conflict of interest: None declared
Citation Format: Tanja Eggersmann, Christoph Riese, Claudia Wenzel, Timo Schinkoethe, Tom Degenhardt, Rachel Wuerstlein, Nadia Harbeck, Manfred Welslau. GERA: A health economic trial to analyze the impact of ehealth in breast cancer care [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 OT3-14-01.
Abstract P1-01-05: Intraoperative three-dimensions MiniiSCANR for determine adequate margin in breast cancer specimens before histopathological examination
Authors: Laohawiriyakamol Suphawat , Wangkulankul Piyanun , Woodtichartpreecha Piyanoot , Puttawibul Puttisak 
Published: March 2020

Abstract
Background: 20-30% of breast conserving surgery patients undergo a second re-excision procedure due to tumor-positive margins at final histopathology. Various modalities are used to assess the adequacy of surgical resection to minimize positive margin and reoperation rates. MiniiSCAN™ is a method of intraoperative specimen radiography that allows for margin evaluation following excisional breast lesion either BI-RADS 4 and 5. The mechanism of MiniiSCAN™ is similar to computer tomography but specimen is rotated on the plate instead circular rotating frame with an x-ray tube mounted on 1 side and a detector on the opposite side in conventional computerized tomography scan. It is easily and short time to reconstructed into 3 dimensions. This machine was developed by Songklanagarind hospital and National Science and Technology Development Agency, Thailand.
Objective: To evaluate the efficacy of MiniiSCAN™ as a surgical margin guidance tool compared with pathological margin in breast cancer specimens.
Materials & Methods: A retrospective review was designed, 62 consecutive cases of abnormal mammogram (BI-RADS 4,5) with or without wire localization from 1 June 2016 to 30 June 2019 were identified from the electronic medical records at Prince of Songkla University.
Results: Of the 62 specimens imaged, 17 had invasive cancer and ten had in-situ pathological diagnoses. Of these, 10 patients had a positive tumor margin and 17 a negative tumor margin at final histopathology. Margin status evaluation by MiniiSCAN™ reconstruction were calculated in 4 minutes (acquisition and reconstruction time). Of the 27 specimens readings, the margin status in 24 patients was correctly predicted by MiniiSCAN™. There were two false-negative predictions. The accuracy, sensitivity, specificity, positive predictive value and negative predictive value of MiniiSCAN™ in margin status prediction were 88.89%, 80%, 94.11%, 88.89% and 88.89%, respectively.
Conclusion: MiniiSCAN™ could be integrated into routine care, enabling the surgical team to perform and interpret specimen radiographs rapidly and make immediate surgical decisions.
Keywords: Abnormal mammography, Breast cancer, CT scan, Specimen radiography
Citation Format: Suphawat Laohawiriyakamol, Piyanun Wangkulankul, Piyanoot Woodtichartpreecha, Puttisak Puttawibul. Intraoperative three-dimensions MiniiSCANR for determine adequate margin in breast cancer specimens before histopathological examination [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 P1-01-05.
Abstract P1-01-08: Optical metabolic imaging of the effects of acute and intermittent hypoxia in murine breast cancer cells
Authors: Rebello Lisa , Rajaram Narasimhan 
Published: March 2020

Abstract
About 90% of the patients diagnosed with breast cancer succumb due to metastases and not from primary tumor. There are currently few methods that can distinguish indolent and aggressive breast tumors. Recent studies have shown differences in the metabolic profiles of primary, circulating, and metastatic breast cancer cells. One of the key regulators of metastases in breast cancer is the transcription factor Twist. The goal of our study was to determine the relationship between Twist expression and cellular metabolism, and the effect of this relationship on metastatic potential. Multiphoton microscopy can provide non-invasive, label-free and reproducible measurements of cellular metabolism. An optical redox ratio of endogenous fluorescence from nicotinamide adenine dicnucleotide (NADH) and flavin adenine dinucleotide (FAD) (calculated as FAD/NADH+FAD) can reflect the balance between mitochondrial oxidative phosphorylation and glucose catabolism in the cell. Because hypoxia is known to promote metastasis, we studied the effect of both intermittent and acute hypoxia on cellular metabolism in 4T1 murine breast cancer cells. We generated a 4T1-Twist− cell line using CRISPR-Cas9 technology. Western blots of Twist protein expression confirmed that Twist expression was significantly lower in the selected cell population compared with the parental 4T1 line. Both cell lines were exposed to 0.5% oxygen for 3 hours and one hour of reoxygenation (acute hypoxia), and 3 cycles of one-hour hypoxia followed by one-hour reoxygenation (intermittent hypoxia). Multiphoton imaging of endogenous fluorescence as well as metabolic flux analysis (Seahorse Biosciences) was performed for both hypoxic exposures in both cell lines. Our results indicate a significant increase in the optical redox ratio in 4T1 cells when exposed to acute hypoxia, indicating a possible increase in oxidative metabolism. There were no signfiicant differences in the 4T1-Twist− line. On the other hand, we observed a decrease in the optical redox ratio in response to intermittent hypoxia in the 4T1 cells and the opposite effect in the 4T1-Twist− line. In addition to these cell lines, we will also present data from sibling cell lines of the 4T1 with varying Twist levels and hence metastatic potential. These data indicate indicate potentially measurable metabolic differences between indolent and aggressive breast cancer cells when subject to a hypoxia-reoxygenation regimen.
Citation Format: Lisa Rebello, Narasimhan Rajaram. Optical metabolic imaging of the effects of acute and intermittent hypoxia in murine breast cancer cells [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 P1-01-08.
Abstract P1-03-05: Patient-derived xenografts in humanized mice classify metastatic potential of primary triple negative breast cancer
Authors: Yu Chun I , Wu Te-Chia , Kim Kyung In , Menghi Francesca , Oliveira Vanessa , Marches Florentina , Liu Edison T , Banchereau Jacques , Palucka Karolina 
Published: March 2020

Abstract
Triple-negative breast cancer (TNBC) is a particularly aggressive form of breast cancer with high risk of recurrence and approximately 22% rate of five-year survival when the disease becomes metastatic. Thus, understanding of mechanisms supporting metastatic colonization of distant organs is of critical importance for the development of new therapies and possibly improved outcomes. Syngeneic mouse models suggest the role of innate immune cells, particularly neutrophils, in support of metastatic dissemination of TNBC. However, it is not possible to study human cancer in immunocompetent mice. Furthermore, organoids or other 3D tissue models do not allow investigations of distant organs colonization with metastatic TNBC tumors. Here, we used humanized mice and patient-derived xenograft (PDX) from treatment naïve primary TNBC tumors to investigate the mechanisms that promote metastasis. NSG mice with transgenic expression of human hematopoietic cytokines SCF/GM-CSF/IL-3 were engrafted with human CD34+ hematopoietic progenitor cells (HPCs) to generate humanized (h)NSG-SGM3 mice. All eleven (11) analyzed to date PDX tumors grew after orthotopic implantation at week 8-12. The presence of distant metastasis was determined by macroscopic evaluation of distant organs and further confirmed by E-cadherin and cytokeratin 19 expression using polychromatic immunofluorescence on frozen tissue section. Among 11 PDX tumors tested, five did not develop metastasis, four developed only lung metastasis and two developed multi-organ metastasis (lung and liver). Transcriptional profiling with RNAseq revealed significant differences in the immune landscape of primary and metastatic tumors. In particular, liver metastases were enriched in myeloid and plasma cell transcripts. Further analysis is ongoing to uncover specific pathways involved. Thus, our model enables mechanistic and pre-clinical studies of human TNBC metastasis.
Citation Format: Chun I Yu, Te-Chia Wu, Kyung In Kim, Francesca Menghi, Vanessa Oliveira, Florentina Marches, Edison T Liu, Jacques Banchereau, Karolina Palucka. Patient-derived xenografts in humanized mice classify metastatic potential of primary triple negative 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 P1-03-05.
Abstract P1-03-09: The role of E2F5 in breast cancer progression and metastasis
Authors: To Briana , Andrechek Eran Robert 
Published: March 2020

Abstract
Advances in cancer genomics and transcriptomics have provided a better understanding of the diverse genetic landscape driving breast cancer pathogenesis. Despite these advances, the molecular drivers of triple negative breast cancer, an aggressive and heterogenous disease, remains highly elusive. Utilizing a genomic approach, we examined genetic differences across mouse models of breast cancer and identified a gene that was consistently deleted in basal-like mouse models, the predominant intrinsic subtype of triple negative breast cancer. Specifically, we identified a consistent deletion in the transcription factor E2F5. In human breast cancer, E2F5 activity and expression is associated with better overall survival and relapse free survival. To further study the role of E2F5 in breast cancer, E2F5 was deleted in the mammary gland of FVB mice (E2F5cKO) through the use of a cre-lox system driven by the MMTV promoter. E2F5cKO mouse demonstrated a delay a mammary outgrowth, suggesting a potential role in mammary gland development. E2F5cKO mice were aged and observed for tumor development. This revealed mammary tumor formation after an extended latency of 19 months. The resulting mammary tumors demonstrated diverse histological patterns. E2F5cKO tumors also demonstrate high metastatic potential with 70% of tumor bearing mice developing metastasis to the lung. In addition, E2F5cKO tumors have a propensity to metastasize to axillary lymph nodes when transplanted into MMTV-Cre mice, a unique feature that is not commonly observed in other mouse models of breast cancer. To begin to understand the mechanism of tumor progression in E2F5cKO mice, differential gene expression was performed on gene expression data derived from E2F5 or GFP overexpression Human Mammary Epithelial Cells. The resulting differentially expressed genes were further filtered based on fold change, established role in cancer, potential E2F binding site and gene ontology. One of the leading candidates that arose from this analysis was KRas, an oncogene that is highly implicated in tumorigenesis. KRas expression negatively correlated with E2F5 expression. Using a bioinformatic approach, we demonstrated that this inverse relationship between KRas and E2F5 appears to be conserved in human breast cancer. Given this inverse relationship between E2F5 and KRas, we postulate that E2F5 deletion in the mammary gland of mice leads to increased KRas activity. Consistent with our hypothesis, western blot analysis revealed high activity in two major KRas signaling pathways, Akt and Erk, in the majority of E2F5cKO tumors. Together, this preliminary data suggest that E2F5 may behave as a tumor suppressor by negatively regulating the oncogene KRas.
Citation Format: Briana To, Eran Robert Andrechek. The role of E2F5 in breast cancer progression and metastasis [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 P1-03-09.