bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract PS14-06: Changes in management of breast cancer patients during first wave of COVID19, throughout the area of Kent, United Kingdom. An audit of ESMO guideline implementation
Authors: Rodney Simon N , Abson Charlotte , Burcombe Russell , Jyothirmayi Rema , Harper-Wynne Catherine 
Published: February 2021

Abstract
Background: The global COVID-19 pandemic has placed unprecedented burden on individual oncology patients, oncology departments, hospitals and national health systems. In order to protect individual patients from the risk of COVID-19 infection as well as improve capacity for COVID-19 patient management, a series of national and internationally agreed measures were proposed. During the first wave of infections the virulence and effect on cancer patients was not known. It is vitally important that the measures implemented to combat these risks are assessed and evaluated in order to learn best how to manage potential future waves of known and unknown viral infections.Methods: The international ESMO COVID-19 guidelines and national (NICE) guidelines were implemented across Kent, UK. All changes to treatment regimens were audited to assess what were the most frequent changes and in which patient groups could these be implemented. Data was subdivided for both early and advanced breast cancer as well as ER+, HER2+ or triple negative disease.Results: We collected full treatment history from 1,718 breast cancer patients currently receiving active oncology treatments. We were able to change treatment regimens due to COVID19 for 32.8% of patients. Of these 27.1% were early breast cancer patients compared with 43.7% were those with advanced metastatic disease. The most common changes for neoadjuvant changes were proceeding to surgery before completion of planned chemotherapy (10.2%), switch to 3 weekly Paclitaxel (10%) and chemotherapy break (8%). For adjuvant patients the most common changes included postponement of bisphosphonates (70.8%), chemotherapy break (13.5%), and curtailment to 6 months of adjuvant Trastuzumab (10.4%). For our palliative patients the most common changes included delay CDK4/6 inhibitor treatment (79.2%), postponement of bisphosphonates (24.8%), break in HER2 antibody (9.6%) and break in chemotherapy (8%).Conclusions: A large proportion of breast cancer oncology patients were deemed suitable to have a change in original planned treatment. We are fortunate to have comparatively large number of treatment options that can be customised on a patient basis to individual reduce risk of COVID-19. Further analysis is needed over time to compare the oncological outcomes of those in whom treatment was changes from the current gold standards of care.
Citation Format: Simon N Rodney, Charlotte Abson, Russell Burcombe, Rema Jyothirmayi, Catherine Harper-Wynne. Changes in management of breast cancer patients during first wave of COVID19, throughout the area of Kent, United Kingdom. An audit of ESMO guideline implementation [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS14-06.
Abstract PS14-13: National comprehensive cancer network (NCCN) recommendations for drugs without US food and drug administration (FDA) approval in metastatic breast cancer: A cross-sectional study
Authors: Etan Tal , Amir Eitan , Tibau Adriana , Yerushalmi Rinat , Moore Assaf , Shepshelovich Daniel , Goldvaser Hadar 
Published: February 2021

Abstract
Background: NCCN guidelines include recommendations not approved by the FDA. We aimed to compare the NCCN recommendations for metastatic breast cancer (MBC) with the FDA approved indications and to identify characteristics that are associated with NCCN recommendations for off-label treatment. Methods: All NCCN recommendations for MBC and their supporting data were identified. Drug labels were reviewed to determine whether recommendations are FDA approved indications. Odds ratio (OR) and 95% confidence interval (CI) were calculated to compare between FDA approved and off-label recommendations for pre-specified categories including drug type, tumor subtype, level of recommendation and line of therapy. Results: Of 124 recommendations identified, 68 (55%) were off-label. Chemotherapy and human epidermal growth factor receptor 2 (HER2) targeted drugs were associated with less frequent approved indications (OR=0.28, 95% CI 0.12-0.62, p=0.001 and OR=0.29, 95% CI 0.12-0.70, p=0.005, respectively). Recommendations for endocrine therapy (OR=3.44, 95% CI 1.32-9.09, p=0.009) and non-HER2 targeted treatment (OR=10.0, 95% CI 3.03-33.33, p&lt;0.001) were associated with FDA approved indications. Compared to combination therapies, monotherapies were more likely to be FDA approved (OR=3.45, 95% CI 1.64-7.23, p=0.001). Category 1 (OR=7.63, 95% CI 2.19-26.55, p=0.001) and preferred NCCN recommendations (OR=5.49, 95% CI 2.36-12.77, p&lt;0.001) were more likely to be FDA-approved indications. Compared to off-label recommendations, NCCN recommendations of approved drugs were based on significantly higher sample size (mean 477 vs. 342 patients, p=0.017) and were non-
significantly associated with availability of randomized data (OR=1.92, 95% CI 0.87-4.24, p=0.10).Conclusion: More than half of all NCCN recommendations for MBC are off-label, mostly involving chemotherapy containing regimes for HER2 negative disease and combinations which include HER2 targeting drugs. The clarity of the NCCN guidelines can be improved by underlining the strength of the evidence supporting various recommendations for MBC and the hierarchy between various treatment options.
Citation Format: Tal Etan, Eitan Amir, Adriana Tibau, Rinat Yerushalmi, Assaf Moore, Daniel Shepshelovich, Hadar Goldvaser. National comprehensive cancer network (NCCN) recommendations for drugs without US food and drug administration (FDA) approval in metastatic breast cancer: A cross-sectional study [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS14-13.
Abstract PS14-16: Novel iodine nanoparticle micro-localization and resultant radiotherapy-enhancement of triple negative human breast cancer growing in the brains of athymic nude mice
Authors: Ridwan Sharif M , Hainfeld James F , Stanishevskiy Yaroslav , Ross Vanessa , Smilowitz Henry M 
Published: February 2021

Abstract
About 30% of breast cancers metastasize to brain; those widely disseminated are fatal typically in 3-4 months, even with the best available surgery, drugs, and radiotherapy. To address this dire situation, we have developed iodine nanoparticles (INPs) that target brain tumors after intravenous (IV) injection. The iodine then absorbs X-rays during radiotherapy (RT), creating free radicals and local tumor damage, effectively boosting the local RT dose at the tumor. Efficacy was tested using the very aggressive human triple negative breast cancer (TNBC, MDA-MB-231 cells) growing in the brains of athymic nude mice. With a well-tolerated non-toxic IV dose of the INPs (7 g iodine/kg body weight), tumors showed a heavily iodinated rim surrounding the tumor having an average uptake of 2.9% iodine by weight (peaks at 4.5%), calculated to provide dose enhancement factors of ~5.5 (peaks at 8.0) – the highest ever reported for any radio-enhancing agents. With 15-Gy, single dose RT, all animals died by 72 days; INP pretreatment resulted in longer-term remissions with 40% of mice surviving 150 days and 30% surviving &gt; 280 days (Hainfeld et al., 2020). Fluorescence confocal microscopy revealed most INP staining co-localized with CD31 in the tumor center and tumor periphery. Greatest INP and CD31 staining was in the tumor periphery, the region of increased Micro CT contrast. Tumor cells are seen to line irregularly-shaped spaces (ISS) with INP and CD31 staining very close to or on the tumor cell surface and with PAS stain on their boundary and may represent a unique form of CD31-expressing vascular mimicry in intracerebral 231-tumors. INP and CD31 co-staining is also seen around ISS formed around tumor cells migrating on CD31 positive blood-vessels. We hypothesize that breast cancer cells secrete a CD31 containing scaffold to which IV-injected INPs bind; tumor cells proliferate along the scaffold forming the boundaries of the ISS creating a form of vascular mimicry. The significant radiation dose enhancement to the prolific INP-binding ISS found throughout the tumor but concentrated in the tumor rim, may contribute significantly to the life extensions observed after INP-RT; vascular mimicry could represent a new nanoparticle, particularly INP, tumor-homing target.
Citation Format: Sharif M Ridwan, James F Hainfeld, Yaroslav Stanishevskiy, Vanessa Ross, Henry M Smilowitz. Novel iodine nanoparticle micro-localization and resultant radiotherapy-enhancement of triple negative human breast cancer growing in the brains of athymic nude mice [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS14-16.
Abstract PS15-03: Breast complications in patients who received intraoperative radiation therapy compared to other forms of radiation therapy following breast conserving surgery
Authors: Wheeler James , Vaghefi Houman , Morris Laura , Liu Fang , Sparks Irina , Denham Fiona , Henry Leonard , Hardy Ashley , Schrock Meghan , DePue Vanessa , Coody Leon 
Published: February 2021

Abstract
Introduction: Intraoperative radiation therapy (IORT) is a convenient treatment option for appropriate women with early stage breast cancer. Some patients undergoing IORT also need adjuvant whole breast radiation therapy due to adverse final pathologic features. Although there are various reports of the complication rates with patients undergoing IORT, comparisons with patients undergoing other forms of radiation therapy such as whole breast or accelerated partial breast radiation are sparse. Methods: A total of 293 patients underwent breast conserving surgery at the study institution between January 2016 and December 2019 for either ductal carcinoma in situ (DCIS) or invasive breast cancer. Three patients had bilateral breast cancer and one patient had a local recurrence having refused adjuvant treatment following breast conserving surgery, for a total of 297 treated breasts. 124 received whole breast radiation therapy, 70 did not receive radiation therapy, 47 received IORT alone, 15 received IORT and whole breast radiation therapy, 30 received accelerated partial breast radiation using external beam radiation (APBI-EB), and 9 received Ir-192 based high dose rate accelerated partial breast radiation (APBI-HDR). One patient with bilateral breast cancer did not complete whole breast radiation therapy to either breast. Complications included cellulitis, wound drainage, symptomatic seroma, delayed wound healing, and wet desquamation. Interventions included observation, antibiotics, wound packing, debridement, fluid aspiration, hydrogel dressings, and wound vacuums. Results: For the entire group, the incidence of wound complications was 20%. The risk of complications was 27.4% for those undergoing IORT (with or without whole breast radiation) compared to 18.3% for those not receiving IORT, which was not statistically different at the 5% significance level. For those who received both IORT and whole breast radiation, however, the proportion having complication was 53.3% versus 18.4% in the other groups. The difference was significant with a p-value 0.0032. Conclusion: Patients who undergo both IORT and whole breast radiation have an increased risk for wound complications.
Citation Format: James Wheeler, Houman Vaghefi, Laura Morris, Fang Liu, Irina Sparks, Fiona Denham, Leonard Henry, Ashley Hardy, Meghan Schrock, Vanessa DePue, Leon Coody. Breast complications in patients who received intraoperative radiation therapy compared to other forms of radiation therapy following breast conserving surgery [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS15-03.
Abstract PS15-11: Intraoperative radiation therapy (IORT) for1200 early breast tumors
Authors: Epstein Melinda , Silverstein Melvin , Chen Peter , Lin Kevin , Kim Brian , Khan Sadia , Snyder Lincoln , Guerra Lisa E. , Coleman Colleen 
Published: February 2021

Abstract
Introduction: Two prospective randomized trials, TARGIT-A and ELIOT, have shown intraoperative radiation therapy (IORT) to be a safe alternative with a low-risk of local recurrence compared to whole breast radiation therapy following breast conserving surgery for selected low-risk patients. We report the first 1200 tumors treated with this modality at our facility.Methods: 1200 distinct breast cancers in 1169 patients (31 bilateral) were treated with breast conserving surgery and X-ray IORT, using the Xoft Accent System from June 2010 to November 2018. Patients were enrolled in an IORT registry trial and data were collected at 1 week, 1 month, 6 months, 1 year, and yearly thereafter. The primary endpoint was local recurrence.Results: To date, there have been 61 events in 54 patients: 50 ipsilateral local recurrences (14 DCIS and 36 invasive), 7 regional nodal recurrences and 4 distant recurrences. Of local recurrences, 9 were within the IORT field, 21 outside of the IORT field but within the same quadrant as the index cancer, and 20 were new cancers in different quadrants. There has been no breast cancer related deaths and 27 non-breast cancer deaths. Currently, with a median follow-up of 52 months, Kaplan Meier analysis projects 5.2 % local recurrence rate at 5 years. In the table below, the five-year probability of local recurrence is analyzed by quadrant and/or type of recurrence (all recurrences or just invasive). Using the 2017, ASTRO Categories, 520 patients (43%) were suitable for IORT, 415 (35%) were cautionary, and 265 (22%) were unsuitable for IORT after final histopathology was evaluated.Conclusion: IORT is profoundly convenient. When used as the only adjuvant breast irradiation, it eliminates approximately 15-35 outpatient visits. This has become increasingly important during the current COVID-19 pandemic. In the group of patients described here, more that 100,000 patient-hours were saved. The local, regional, and distant recurrence rates observed in this trial were slightly higher than those of the prospective randomized TARGIT-A and ELIOT Trials. This may be explained by 22% of our patients being considered unsuitable for IORT by ASTRO Criteria. The low complication rates previously reported by our group as well as the low recurrence rates reported in this study support the cautious use and continued study of X-ray IORT in women with low-risk breast cancer.
Citation Format: Melinda Epstein, Melvin Silverstein, Peter Chen, Kevin Lin, Brian Kim, Sadia Khan, Lincoln Snyder, Lisa E. Guerra, Colleen Coleman. Intraoperative radiation therapy (IORT) for1200 early breast tumors [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS15-11.
Abstract PS15-13: Safe margins for delineation of left anterior descending artery (LAD) using cardiac-gated CT-scan (CG-CT) in left side breast cancer patients
Authors: Nicolas Eliot , Khalifa Nadjoua , Bouhroum Sabrina , Laporte Cyril , Kirova Youlia 
Published: February 2021

Abstract
Background: Cardiac toxicity after breast cancer (BC) radiotherapy (RT) is partly due to the large radiation doses to coronary arteries. The left anterior descending artery (LAD) is particularly exposed. A first step in achieving robustly proven dose constraints to the LAD during treatment planning is homogeneous delineation based on guidelines. LAD delineation can be problematic due to heart movements.Purpose/Objective(s): The aim of the study was to establish a safety margin for delineation of the LAD in BC patients.Materials/Methods: We studied 45 left-sided BC patients who had an indication for adjuvant radiotherapy between 2015 and 2018. They all underwent cardiac-gated computed tomography scan (CG-CT), as well as planning CT scans (P-CT) with or without contrast agents, to assess LAD diameter and movements. CG-CT was performed while monitoring the cardiac cycle. Acquisition was launched immediately after contrast injection (arterial sequence), with deep inspiration breath hold and use of a beta-receptor blocking agent. By manually reviewing each scan, the LAD positions and diameter were defined at 20 different phases of the cardiac cycle at 5 different sites: ostium, circumflex (Cx) bifurcation (bfc), first diagonal (D1) bfc, second diagonal (D2) bfc and apex (right coronary anastomosis). Next step is to introduce it in softwear of automatic delineation to improve the atlas of cardiac structures.Results: Movement of the LAD is maximal at the ostium, then constant overall even when far from its origin. The diameter decreases with the distance from ostium: 4.9 mm (OS), 3.9 mm (Cx), 3.5 mm (D2) and 3.1 mm (D2).Conclusion: We suggest using a safety delineation margin consisting of a cylinder with a diameter of 10 mm surrounding the LAD. These findings must be validated in independent series of patients treated for BC.
Citation Format: Eliot Nicolas, Nadjoua Khalifa, Sabrina Bouhroum, Cyril Laporte, Youlia Kirova. Safe margins for delineation of left anterior descending artery (LAD) using cardiac-gated CT-scan (CG-CT) in left side breast cancer patients [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS15-13.
Abstract PS16-10: Tao kinase 3 augment the resistance to microtubule-disrupting agents in breast cancer cells
Authors: Fang Chih-Yeu , Lai Tsung-Ching , Hsiao Michael 
Published: February 2021

Abstract
Breast cancer is the leading type of cancer in women worldwide. It is a heterogeneous disease that contains several subtypes with substantial differences in pathology and clinical outcome. With the advancements in imaging and targeted therapy, many patients with early stages of this disease have a great opportunity to be cured. However, recurrence or metastasis of tumor still occurs in patients even after successful primary treatment. Chemotherapy remains one of the most important treatment for advanced breast cancer. Anti-microtubule agents including taxanes, eribulin and vinca-alkaloids constitutes the major anti-breast cancer chemotherapeutic category, while chemoresistance remains a thorny issue for advanced disease. We aimed to discover novel candidate regulators for chemoresistance in breast cancer. A lentiviral-based, high-throughput shRNA platform was developed for screening the variation of global kinome to find new therapeutic targets in paclitaxel-resistant breast cancer cells. The underlying molecular mechanisms was further explored by global phosphoprotein array and expression microarray. The serine/threonine kinase, TAO Kinase 3 (TAOK3), was identified from 724 kinase genes. Knockdown of TAOK3 exhibited the most profound reduction of IC50 values in response to paclitaxel treatment in breast cancer cells. High expression of TAOK3 was related to poor prognosis in breast cancer patients after adjuvant chemotherapy. Furthermore, the expression of TAOK3 also decreased the sensitivity to other anti-microtubule drugs, including eribulin and vinorelbine. Expression microarray analysis revealed that NF-κB signaling plays the major regulation roles in TAOK3-associated resistance. Taken together, our results showed that TAOK3 increases resistance to anti-microtubule drug through upregulating the NF-κB signaling in breast cancer. Inhibitors that disrupt TAOK3 and NF-κB signaling pathway may overcome the drug resistance for patients treated with anti-microtubule agents.
Citation Format: Chih-Yeu Fang, Tsung-Ching Lai, Michael Hsiao. Tao kinase 3 augment the resistance to microtubule-disrupting agents in breast cancer cells [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS16-10.
Abstract PS16-16: B-catenin-ccl2 axis regulates breast cancer stem cells via crosstalk between cancer cells and tumor-associated macrophages
Authors: Liu Hao , Liu Bolin 
Published: February 2021

Abstract
Breast cancer is most frequently diagnosed cancer among women worldwide. Though advance in diagnosis and treatment strategies have prolonged disease-free survival (DFS) and overall survival (OS) for different molecular types of breast cancer patients, many patients initially benefit from chemotherapy but experience recurrence, metastasis, and ultimately death. Breast cancer stem cells (BCSCs) are tumor initiating cells with self-renewal, low differentiation, and high tumorigenicity and metastasis abilities. The ineffectiveness of conventional chemotherapy to eradicate BCSCs frequently results in therapy failure. Therefore, understanding the molecular pathways sustaining BCSC characteristics and targeting BCSCs will ultimately improve breast cancer treatments. Here, we found that activation of β-Catenin directly regulated CCL2 expression at the transcriptional level, and in turn, promoted tumor-associated macrophage (TAM) infiltration and M2 polarization. Moreover, crosstalk between the TAM and breast cancer cells increased secretion of CCL2, which promoted cancer progression by regulating BCSCs characteristics through feedback activation of β-Catenin. The combined inhibition of CCR2 and β-catenin synergistically suppressed breast cancer growth. The results described herein provide novel insights into our understanding how the β-Catenin-CCL2 feedback loop mediates the crosstalk between cancer stem cells and tumor-associated macrophages. They may also facilitate the development of useful therapeutic targets against BCSCs for breast cancer therapy.
Citation Format: Hao Liu, Bolin Liu. B-catenin-ccl2 axis regulates breast cancer stem cells via crosstalk between cancer cells and tumor-associated macrophages [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS16-16.