bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P1-10-16: Cardiac conduction system exposure with modern radiotherapy techniques for breast cancer irradiation
Authors: Loap Pierre , Goudjil Farid , De Marzi Ludovic , Servois Vincent , Kirov Krassen , Fourquet Alain , Kirova Youlia M. 
Published: March 2023

Abstract
Introduction: Exposition of cardiac conduction system during breast radiotherapy has never been studied, despite increasing use of intensity modulated radiotherapy which expose larger volume to low dose bath. We evaluated conduction node exposure during breast irradiation with volumetric modulated arctherapy (VMAT) and estimated the potential dosimetric benefit with intensity modulated protontherapy (IMPT). Materials and methods: Atrioventricular (AVN) and sinoatrial (SAN) nodes were retrospectively delineated according to published guidelines on the simulation CT scans of twelve breast cancer patients having undergone conserving surgery and adjuvant locoregional VMAT. IMPT treatment was re-planned on the simulation CT scans for all breast cancer patients. Mean and maximum doses to the SAN and the AVN were retrieved and compared. Correlation coefficients were calculated between doses to the SAN or the AVN and to the whole heart. Results: Average mean doses to the SAN and to the AVN were 2.8 Gy and 2.3 Gy respectively for left-sided irradiation and 9.6 Gy and 3.6 Gy respectively for right-sided irradiation. Average maximum doses to the SAN and to the AVN were 3.5 Gy and 2.8 Gy respectively for left-sided irradiation and 13.1 Gy and 4.6 Gy respectively for right-sided irradiation. IMPT significantly reduces doses to conduction nodes. Correlations between doses to the SAN or the AVN and the whole heart were usually significant. Conclusion: SAN and AVN can be substantially exposed during breast VMAT, especially for right-sided irradiation. Cardiotoxicity studies evaluating conduction node exposure might define dose constraints and criteria for additional cardiac sparing techniques, such as respiratory techniques or proton therapy, which could be beneficial to patients with underlying rhythmic or conduction disorders.
Citation Format: Pierre Loap, Farid Goudjil, Ludovic De Marzi, Vincent Servois, Krassen Kirov, Alain Fourquet, Youlia M. Kirova. Cardiac conduction system exposure with modern radiotherapy techniques for breast cancer irradiation [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 P1-10-16.
Abstract P1-14-04: A Phase 0 Clinical trial of Sacituzumab Govitecan in Patients with Breast Cancer Brain Metastases and Recurrent Glioblastoma
Authors: Ghamasaee Pegah , Balinda Henriette , Brenner Andrew , Floyd John 
Published: March 2023

Abstract
Purpose: Sacituzumab govitecan has shown efficacy and acceptable tolerability in a multicenter phase I/II clinical trial (NCT01631552) in patients with advanced epithelial cancers. Our study was initiated to determine the bioavailability of Sacituzumab govitecan (SG) in breast brain metastasis and glioblastoma. The goals were to evaluate the extent by which SG can penetrate the blood brain barrier and access tumor tissues by testing free SN-38, SN-38G and total SN-38 concentrations in tumor tissue, serum, and CSF. Patients and methods: Patients diagnosed with brain metastatic breast cancer and recurrent glioblastoma were enrolled in a single-center clinical phase 0 study to receive a single intravenous dose of SG at 10 mg/kg one day before surgical resection. Tumor and corresponding serum were collected during surgery to measure their levels of SN-38 and its metabolites. Following recovery, patients resumed SG treatment at 10 mg/kg on days 1 and 8 of 21-day cycles and were assessed for responses by MRI every third cycle using response assessment in neuro-oncology (RANO) criteria. Total Sn-38 levels were quantified in tumor tissue and corresponding serum from the patients. Trop-2 and carbonic anhydrase IX (CAIX) expression was investigated by IHC. SG activity was tested in a breast cancer intracranial mouse model. Results: An average of 2365 ng/ml in serum and 132 ng/g in tissue of total SN-38 was quantified in our patient samples. Trop-2 expression was observed in 90% of patient tumors. 40% of the samples showed high expression of CAIX. SG significantly inhibited tumor growth in vivo and increased overall survival. 20% of patients in the breast cancer arm of the trial demonstrated a complete response by RANO criteria and the remaining 80% of patients demonstrated a partial response. Ultimately, 80% of the patients in the breast cancer metastasis arm survived. Conclusion: Sacituzumab govitecan is an effective drug that crosses the blood brain barrier to inhibit the growth of metastatic breast cancer to the brain after tumor resection surgery.
Citation Format: Pegah Ghamasaee, Henriette Balinda, Andrew Brenner, John Floyd. A Phase 0 Clinical trial of Sacituzumab Govitecan in Patients with Breast Cancer Brain Metastases and Recurrent Glioblastoma [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 P1-14-04.
Abstract P2-11-15: Focal ESR1 gene amplification is an independent prognostic marker in postmenopausal patients with endocrine-responsive early breast cancer
Authors: Singer Christian F. , Holst Frederik , Steurer Stefan , Burandt Eike , Lax Sigurd , Jakesz Raimund , Rudas Margaretha , Stöger Herbert , Greil Richard , Sauter Guido , Filipits Martin , Simon Ronald , Gnant Michael 
Published: March 2023

Abstract
Purpose: Estrogen receptor (ER) expression predicts response to endocrine therapy and is a prognostic biomarker. However, no ER-associated biomarker is able to identify patients with particularly favorable outcome among ER+ tumors. We investigated the value of ESR1 amplification in predicting long-term outcome in tamoxifen-treated postmenopausal women with early breast cancer with and without nodal involvement. Patients and Methods: 394 patients with ER+ breast cancer (235 node-negative, 159 patients node- positive), who had received adjuvant tamoxifen for 5 years in the prospective randomized ABCSG-06 trial, and in whom FFPE tumor tissue was available, were included in this analysis. ER alpha immunoreactivity was evaluated using the Allred score, while ESR1 gene amplification was evaluated by FISH analysis. Results: Focal ESR1 amplification was detected in 187 (47%) tumors, and was associated with a favorable outcome. After a median follow-up of 10 years, women with focal ESR1 amplification had a significantly longer distant recurrence-free survival (DRFS; adjusted HR 0.48; 95% CI 0.26-0.91; p=0.02) and breast cancer-specific survival (BCSS; adjusted HR 0.47; CI 0.27-0.80; p=0.01) compared to women without ESR1 amplification. The association between ESR1 amplification and improved DRFS and BCSS was only found in node-positive tumors, but not in nodal-negative tumors. ER alpha immunoreactivity, evaluated by Allred score, correlated significantly with focal ESR1 amplification (p&lt; 0∙0001; Chi-squared test), but without prognostic significance. Conclusion: We suggest focal ESR1 amplification as predictor of improved long-term outcome in postmenopausal women with node-positive ER+ early breast cancer.
Citation Format: Christian F. Singer, Frederik Holst, Stefan Steurer, Eike Burandt, Sigurd Lax, Raimund Jakesz, Margaretha Rudas, Herbert Stöger, Richard Greil, Guido Sauter, Martin Filipits, Ronald Simon, Michael Gnant. Focal ESR1 gene amplification is an independent prognostic marker in postmenopausal patients with endocrine-responsive early 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 P2-11-15.
Abstract P2-16-03: The Speckle-type POZ protein (SPOP) inhibits breast cancer malignancy by destabilizing oncogene TWIST1
Authors: Wei Chunli , Liu Yun , Liu Xiaoyan , Cheng Jingliang , Fu Jiewen , Xiao Xiuli , Moses Robb E , Li Xiaotao , Fu Junjiang 
Published: March 2023

Abstract
Epithelial-mesenchymal transition (EMT) inducing transcription factor TWIST1 plays a vital role in cancer metastasis. How the tumor-suppressive E3 ligase, Speckle-type POZ protein (SPOP), regulates TWIST1 in breast cancer remains unknown. In this study, we report that SPOP physically interacts with, ubiquitinates, and destabilizes TWIST1. SPOP promotes K63-and K48-linked ubiquitination of TWIST1, predominantly at K73, thereby suppressing cancer cell migration and invasion. Silencing SPOP significantly enhances EMT, which accelerates breast cancer cell migration and invasiveness in vitro and lung metastasis in vivo. Clinically, SPOP is negatively correlated with the levels of TWIST1 in highly invasive breast carcinomas. Reduced SPOP expression, along with elevated TWIST1 levels, is associated with poor prognosis in advanced breast cancer patients, particularly those with metastatic triple-negative breast cancer (TNBC). Taken together, we have disclosed a new mechanism linking SPOP to TWIST1 degradation. Thus SPOP may serve as a prognostic marker and a potential therapeutic target for advanced TNBC patients.
Citation Format: Chunli Wei, Yun Liu, Xiaoyan Liu, Jingliang Cheng, Jiewen Fu, Xiuli Xiao, Robb E Moses, Xiaotao Li, Junjiang Fu. The Speckle-type POZ protein (SPOP) inhibits breast cancer malignancy by destabilizing oncogene TWIST1 [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 P2-16-03.
Abstract P2-17-01: Targeted CRISPR screen to identify synthetic lethal combinations between APOBEC3B and DNA repair
Authors: Stefanovska Bojana , Lin Kevin , Troness Benjamin , Myers Chad , Harris Reuben 
Published: March 2023

Abstract
APOBEC-catalyzed deamination of cytosine bases is the largest enzymatic and second largest overall source of mutation in cancer. One member from the APOBEC family of enzymes, APOBEC3B (A3B) is overexpressed and dysregulated in many different cancer types. In addition to hallmark C-to-T transitions and C-to-G transversions, APOBEC-catalyzed uracil lesions can be processed into single- and double-strand DNA breaks. Therefore, A3B-positive tumors are under continual stress to repair DNA breaks and may be vulnerable to DNA repair inhibition. Previous results from the Harris lab have identified UNG2, DNA uracil glycosylase 2 (UNG2), initiator of the base excision repair pathway, as synthetic lethal pair with A3B. The genetic disruption of UNG2 combined with high expression of A3B, causes cell death. This provides the rational to hypothesize that also other DNA repair proteins could be putative synthetic lethal pairs with A3B, when its expression and activity are high. To test this hypothesis, CRISPR guide RNA library targeting 237 DNA damage repair and response genes was used in doxycycline-inducible TREX-293-A3Bi-eGFP cell line. Cells expressing or not A3B were harvested for DNA extraction and sequencing at different time points. Comparison of guide RNA abundance between doxycycline and H2O treated cells revealed the dropout guides that disrupt genes and create putative synthetic lethal combinations with A3B. The screen design and overall results will be presented
Citation Format: Bojana Stefanovska, Kevin Lin, Benjamin Troness, Chad Myers, Reuben Harris. Targeted CRISPR screen to identify synthetic lethal combinations between APOBEC3B and DNA repair [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 P2-17-01.
Abstract P2-24-01: The development of covalent microtubule stabilizers for drug-resistant cancers
Authors: Essif Jacob N. , Risinger April 
Published: March 2023

Abstract
Microtubule targeting agents (MTAs) are some of the most commonly used and effective chemotherapeutic agents used in the treatment of breast cancer and other solid tumors. Clinically approved MTAs include microtubule destabilizers, such as the vinca alkaloids or eribulin, as well as the taxane class of microtubule stabilizers, including paclitaxel. While MTAs are effective chemotherapeutics, the development of resistance due to drug efflux or changes in β-tubulin isotype expression are major clinical limitations to each the currently approved drugs of this class. One strategy for overcoming drug resistance is the development of drugs that covalently bind to their drug target, which has been validated in the clinic with the success of irreversible EGFR inhibitors in drug resistant non-small cell lung cancer. We have identified the C22,23-epoxytaccalonolides (taccas) as a class of plant-derived microtubule stabilizers that covalently bind to β-tubulin with a high degree of specificity and retain efficacy in drug-resistant models in vitro and in vivo. Although the taccas have potent and persistent antitumor efficacy in vivo, they suffer from a narrow therapeutic index and short serum half-life that provides optimal efficacy when targeted directly to the tumor site. We are undertaking a multipronged approach to generate synthetic tacca analogs (taccalogs) that retain the efficacy of the natural product with improved pharmacokinetic properties, including improved serum binding, to increase half-life and provide better in vivo tolerability. We are also identifying strategies to improve tumor targeting of the taccas, which is being guided by determining their in vivo distribution with radiolabeled analogs. In a complementary approach, we tested the hypothesis that non-covalent microtubule stabilizers that have increased binding affinity to tubulin share properties with the taccas, such as the ability to circumvent drug resistance and provide potent and persistent in vivo efficacy with a more tolerable therapeutic window. Our data suggest that while non-covalent microtubule stabilizers with improved binding compared to paclitaxel provide improved cellular persistence after drug washout and potent antitumor efficacy, they are not able to overcome drug resistance to some degree as covalent inhibitors, demonstrating the advantage of continuing to develop irreversible drugs such as the taccalonolides for the treatment of drug resistant disease.
Citation Format: Jacob N. Essif, April Risinger. The development of covalent microtubule stabilizers for drug-resistant cancers [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 P2-24-01.
Abstract P2-26-12: Interaction between CTCs and platelets complicate their detection by masking surface epitopes
Authors: Schott Dorothea , PIZON Monika , Pachmann Katharina 
Published: March 2023

Abstract
1) Background: It is well known that solid tumors have the ability to form metastases. The development of distant metastases is due to the primary tumor shedding cells that travel to distant sites via the blood vessels. Platelets specifically promote tumor cells survival in the bloodstream. To investigate the interplay between platelets and circulating tumor cells, we implemented our approach to label simultaneously circulating epithelial tumor cells and platelets. 2) Methods: 40 breast cancer patients were enrolled into the study. Blood samples were collected in EDTA tubes without fixatives and processed at 3 timepoints (0h, 24h and 48h) using the maintrac® approach. In order to visualize platelets we used anti-CD36 antibody staining. 3) Results: We observed at 0h post-blood draw platelet aggregates strictly attached to single cells that did not stain with anti-EpCAM antibody. After keeping blood samples at room temperature for 24h platelet aggregates could still be detected, but the anti-EpCAM antibody became accessible to the underlying cells. CTCs were detected in 94% of patients on day 1 post-blood draw. At 48h following initial blood drawing, platelets had almost completely disappeared from the cell surface and the number of detected CTCs remains stable between 24h and 48h. Furthermore, the number of CTCs correlates with clinical stage of disease. Patients with stage I/II have significantly less CTCs as compared to patients with stage III/IV (median 5 vs. 19 CTCs/100µl cell suspension, p&lt; 0.05). 4) Conclusion: Our results suggest that platelets play a key role in masking circulating tumor cells. Masking may explain the difficulties in detection of these cells and prevention of their elimination by the immune system.
Citation Format: Dorothea Schott, Monika PIZON, Katharina Pachmann. Interaction between CTCs and platelets complicate their detection by masking surface epitopes [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 P2-26-12.
Abstract P3-02-01: Chemotherapy plus immunotherapy in stage IV triple-negative breast cancer patient during pregnancy: a case report
Authors: Lima Candice , Apolinario Thiago L. 
Published: March 2023

Abstract
Introduction Cancer during pregnancy is uncommon but the incidence is increasing, particularly in breast cancer, the most common tumor diagnosed in this scenario. The treatment decision in pregnant patients with triple-negative breast cancer is challenging, even more so in cases with advanced disease. Clinical case A 36-year-old woman was referred to our hospital in January, 2020 with the diagnosis of an early (T2N0M0, stage IIA) invasive carcinoma of no special type triple-negative tumor on the left breast and germinative CHEK2 mutation. She received neoadjuvant treatment with four cycles of ACdd followed by nine weeks of paclitaxel and carboplatin, interrupted for local disease progression. The patient underwent a nipple-sparing mastectomy plus sentinel lymph node biopsy without complications. The pathology report showed gross residual disease, so we decided on adjuvant treatment with radiotherapy followed by capecitabine. Twelve months after the end of the treatment, she received the diagnosis of second-trimester pregnancy but also presented suspicion of pulmonary, nodal, and liver relapse. The liver biopsy confirmed triple-negative histology with CPS &gt; 10. The first-line chemotherapy was liposomal doxorubicin, which showed hepatic disease progression after two cycles. As second-line, we started carboplatin, gemcitabine, and pembrolizumab. The radiologic evaluation after two cycles showed a partial response in the lung and liver, with the patient presenting excellent tolerability without fetal complications. The treatment plan is to wait until the term for delivery and continue treatment until progression or toxicity. Conclusion We report the first stage IV triple-negative breast cancer case in a pregnant patient treated with chemotherapy plus immunotherapy. This case indicates that the treatment is feasible and should be considered in this scenario.
Citation Format: Candice Lima, Thiago L. Apolinario. Chemotherapy plus immunotherapy in stage IV triple-negative breast cancer patient during pregnancy: a case report [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 P3-02-01.
Abstract P3-04-06: Artificial intelligence-based triaging of breast cancer screening mammograms and radiologist workload reduction: a systematic review and meta-analysis
Authors: Xavier Debora , Miyawaki Isabele A. , Jorge Carlos Alberto Campello , Moreira Matheus Jose Barbosa , Carvalho Bruno M. , Batalini Felipe 
Published: March 2023

Abstract
Introduction: Deep learning (DL) has shown promising results for mammographic breast cancer diagnosis. However, the impact of artificial intelligence (AI) in the screening process have not yet been fully addressed in terms of workload reduction, which has potential to decrease healthcare disparities. Radiologists are tasked with overwhelming volumes of screening mammograms, particularly in medically underserved areas. Therefore, when applied to workflow improvement, AI might be a tool to reduce healthcare disparities. The purpose of this systematic review and meta-analysis was to assess if AI-based triaging of breast cancer screening mammograms could reduce the radiologist’s workload with non-inferior sensitivity. Methods: PubMed, EMBASE, Cochrane Central and Web of Science databases were systematically searched for studies that evaluated AI algorithms on computer-aided triage of breast cancer screening mammograms. We extracted data from homogenous studies and performed a proportion meta-analysis with random-effects model to verify the radiologist’s workload reduction and the software’s sensitivity. Results: A total of 14 studies were systematically selected. Three studies using the same commercially available DL algorithm were included in the meta-analysis, with 156852 examinations evaluated at the threshold of 8. The radiologist’s workload decreased by 68.3% (95%CI 0.655-0.711, I² = 98.76%, p &lt; 0.001), with a sensitivity of 93.1% (95%CI 0.882-0.979, I² = 83.86%, p = 0.002). Conclusion: Our findings suggest that DL computer-aided triage of breast cancer screening mammograms significantly reduces the radiologist’s workload with high sensitivity. Although AI’s implementation remains complex and heterogeneous, it is a promising tool to optimize healthcare resources with a potential large impact in low resource settings that struggle with workforce shortage.
Citation Format: Debora Xavier, Isabele A. Miyawaki, Carlos Alberto Campello Jorge, Matheus Jose Barbosa Moreira, Bruno M. Carvalho, Felipe Batalini. Artificial intelligence-based triaging of breast cancer screening mammograms and radiologist workload reduction: a systematic review and meta-analysis [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 P3-04-06.