bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P1-05-36: AI-Based Smartphone App Using a Single-Lead ECG for Automated QTc Diagnostics in Oncology
Authors: Schinköthe Timo , Tonk Christian Horst , Harbeck Nadia , Carmelo Vanda , Feliciano Joana Gomes , Wuerstlein Rachel , Küemmel Sherko , Schmidt Annette 
Published: March 2023

Abstract
Introduction: Long QT syndrome is a common cardiotoxic side effect of various anti-tumor drugs. Previous cardiological monitoring of oncological patients is primarily complex and requires for non-internal oncologists a consultation. Therefore, the QTc-Tracker smartphone APP was developed, which enabled a tele-cardiological diagnosis of the QTc time with standard single-lead ECG devices. As a result, diagnosis times could already be reduced by 99%. The further development examined an automatic determination of the QT time using the smartphone APP. However, since single-lead ECG devices are significantly more susceptible to interference, the determination of the QT time is more complex than with 12-lead ECGs. Methods: The QTc-Tracker smartphone APP was developed to determine the QT time. Self-tracker single-lead ECG devices were used to record the lead I signal. The ECG recordings were analyzed in the APP and passed on to an external cardiologist as reference. The APP used artificial intelligence and was trained in the first phase and validated in the second phase. The first phase aimed to improve QT time detection. The results of the APP were compared with the findings of the external cardiologist. In both phases, ECGs from breast cancer patients receiving ribociclib were used. Results: A total of 1889 single-lead ECGs were carried out. 248 of these could not be evaluated (13%). QTc prolongation, according to CTCAE, was diagnosed in 41 cases (2.5%). 878 of the evaluable ECGs were used for the training phase and 763 for the evaluation phase. In the first group (before the improvement), the sensitivity to automatically detect a prolongation of the QT time was 36%, and the specificity was 96%. In the evaluation collective (after the training), the sensitivity went up to 85%, and the specificity was unchanged at 96%. Conclusions: The trained method of the QTc tracker is able to reliably detect a QT time lengthening even without a cardiological diagnosis only by using single-lead self-tracker ECG’s. In the rare cases in which an elongation was not detected, the cardiac diagnosis was only a few milliseconds above the threshold value. This artificial intelligence-based smartphone APP is not intended to replace the cardiological diagnosis, but it can simplify routine processes and help to decide which patients need a cardiological examination more urgently.
Citation Format: Timo Schinköthe, Christian Horst Tonk, Nadia Harbeck, Vanda Carmelo, Joana Gomes Feliciano, Rachel Wuerstlein, Sherko Küemmel, Annette Schmidt. AI-Based Smartphone App Using a Single-Lead ECG for Automated QTc Diagnostics in Oncology [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 P1-05-36.
Abstract P1-09-07: Omission of Axillary Surgery for Ipsilateral Breast Tumor Recurrence with Negative Nodes after Previous Breast-Conserving Surgery: Is It Oncologically Safe?
Authors: Qu Feilin , Lin Caijin , Li Jun-Jie , Shao Zhi-Ming 
Published: March 2023

Abstract
Background: Salvage mastectomy is traditionally recommended for patients who developed ipsilateral breast tumor recurrence (IBTR) in light of the previous breast irradiation. However, it remains controversial whether surgical axillary staging (SAS) is necessary for IBTR patients with negative nodes. This study aimed to evaluate the oncologic safety of omitting SAS for IBTR.
Methods: We retrospectively identified patients who developed invasive IBTR with negative nodes after undergoing breast-conserving surgery (BCS). Patterns of care in nodal staging were analyzed based on prior axillary staging status. Clinicopathologic characteristics and adjuvant treatment of the initial tumor, as well as the IBTR, were compared between SAS and no SAS groups. Kaplan-Meier method and Cox regression model were utilized to compare the loco-regional recurrence-free survival (LRRFS), distant metastasis-free survival (DMFS), and overall survival (OS) rates after IBTR removal between the two groups.
Results: A total of 154 IBTR patients were eligible for final analysis. Compared to no SAS group, SAS group was less likely to undergo ALND (15.1% vs 73.3%, p &lt;  0.001) at initial BCS, had a longer recurrence interval (2.8 vs 2.1 years, p=0.03), and were more likely to have discordant molecular subtype with primary tumor (35.8% vs 12.9%, p=0.001). However, the extent of axillary staging did not affect systemic or radiation recommendations. In the subgroup of patients without previous ALND, the clinicopathologic characteristics were roughly comparable. Pathologic analysis revealed pathologically uninvolved nodal status in approximately 85% of patients receiving SAS at time of IBTR in the overall population and the subgroup (Table 1). No significant differences were observed in LRRFS, DMFS and OS between the two groups (Table 2).
Conclusion: For node-negative IBTR patients, we observed selection bias on the basis of prior ALND, shorter recurrence interval, and concordant molecular subtype favoring no SAS, but comparable LRRFS, DMFS, and OS. These results support wider consideration of sparing SAS in the management of IBTR, especially in patients without previous ALND.
Table 1. Pathologic axillary staging in patients receiving axillary surgery at time of IBTR.
Table 2. Cox regression analysis of LRRFS, DMFS, and OS after IBTR.
Citation Format: Feilin Qu, Caijin Lin, Jun-Jie Li, Zhi-Ming Shao. Omission of Axillary Surgery for Ipsilateral Breast Tumor Recurrence with Negative Nodes after Previous Breast-Conserving Surgery: Is It Oncologically Safe? [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 P1-09-07.
Abstract P2-06-01: Improving the health of women on Aromatase Inhibitors: A pilot controlled dietary and exercise intervention trial
Authors: Carpenter Catherine L. , Master Aashini K. , Julian Olivia , Ben-Nissan Dina , Rakoff Michele , Thames Gail , Li Zhaoping 
Published: March 2023

Abstract
Background: In spite of aromatase inhibitors reducing risk of recurrence and mortality, painful side effects often cause women to discontinue use of the drug. Side effects of aromatase inhibitors include joint and muscle pain, loss of bone mineral density, and impairment of heart functioning. Discontinuation of aromatase inhibitors due to these side effects occur in up to 40% of breast cancer survivors, and consequently risks of recurrence and mortality increase. Objective: We developed two interventions designed to reduce inflammation, alleviate pain and stabilize bone mineral density. Methods: We are currently conducting a pilot parallel intervention trial that is targeted toward alleviating side effects from aromatase inhibitors through dietary and exercise controlled interventions lasting for three months. The dietary intervention is an anti-inflammatory Mediterranean diet designed to decrease inflammation and lessen joint and muscle pain. Participants randomized to the Mediterranean dietary intervention are exclusively consuming food provided by Territory Foods®, an outside food preparation and delivery service, local to Los Angeles. Our exercise intervention is designed to mobilize the joints, and strengthen and reduce bone loss. Participants are visiting the UCLA Kinross gym for three days per week and are undergoing tailored exercise sessions delivered from personal trainers following our bone strengthening intervention protocol. Anthropometric measures, muscle strength, DXA scanning of bone mineral density, peripheral arterial tonometry, pulse wave velocity and biomarkers of inflammation, bone turnover and heart functioning are conducted at baseline, mid- and end of intervention. Results: Our trial is targeted to accrue 20 participants. Thus far we enrolled six participants, with three participants completing the trial. Analysis is ongoing and preliminary results will be presented at the San Antonio Breast Cancer Symposium in December, 2022. Post intervention reports from participants have noted a reduction in pain symptoms, moderate weight loss and increase in muscle strength.
Citation Format: Catherine L. Carpenter, Aashini K. Master, Olivia Julian, Dina Ben-Nissan, Michele Rakoff, Gail Thames, Zhaoping Li. Improving the health of women on Aromatase Inhibitors: A pilot controlled dietary and exercise intervention trial [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 P2-06-01.
Abstract P2-24-07: Combination of complete estrogen receptor antagonist, OP-1250, and CDK4/6 inhibitors enhances tumor suppression and inhibition of cell cycle-related gene expression
Authors: Parisian Alison D. , Palanisamy Gopinath S. , Ortega Fabian , Sapugay Judevin L. , Bodell William J. , Kulp David , Kushner Peter , Harmon Cyrus 
Published: March 2023

Abstract
OP-1250, a complete estrogen receptor antagonist (CERAN) and selective estrogen receptor degrader (SERD), is currently in Phase I/II clinical trials for the treatment of estrogen receptor positive (ER+)/human epidermal growth factor receptor 2 negative (HER2-) breast cancer. OP-1250 has previously demonstrated efficacy in both estrogen receptor 1 (ESR1) wild-type and Y537S mutant breast cancer xenograft models. Inhibitors of cyclin-dependent kinases 4 and 6 (CDK4/6) are a standard first-line treatment for ER+ advanced or metastatic breast cancer in combination with endocrine therapy. To characterize OP-1250 efficacy in this setting, we explored the combination of OP-1250 with CDK4/6 inhibitors palbociclib and ribociclib in ER+/HER2- breast cancer preclinical models, and profiled the transcriptional changes associated with single agent and combination therapy. OP-1250 and CDK4/6 inhibitors were tested alone and in combination in ESR1 wild-type MCF7 and ESR1 Y537S mutant ST941 xenograft models. Higher doses of OP-1250 and either CDK4/6 inhibitor, when given as a monotherapy, suppress tumor growth and increase animal survival, while lower doses of the compounds display a modest or minimal effect on tumor growth or survival. In combination, lower doses of OP-1250 and either CDK4/6 inhibitor result in significantly greater tumor growth suppression (both xenograft models), tumor regression (MCF7) and animal survival (ST491) than each compound individually. RNA sequencing revealed substantially more gene expression changes with combination treatment than monotherapy. In particular, pathways associated with cell cycle progression displayed greater changes with combination treatment, similar to what was observed with a much higher dose of monotherapy. This study supports the clinical evaluation of OP-1250 in combination with CDK4/6 inhibitors (palbociclib or ribociclib) and provides additional context to mechanisms of combination efficacy. OP-1250 is currently being evaluated in a Phase Ib clinical trial in combination with palbociclib and a study including evaluation of the combination of OP-1250 with ribociclib is planned to initiate in Q3 2022.
Citation Format: Alison D. Parisian, Gopinath S. Palanisamy, Fabian Ortega, Judevin L. Sapugay, William J. Bodell, David Kulp, Peter Kushner, Cyrus Harmon. Combination of complete estrogen receptor antagonist, OP-1250, and CDK4/6 inhibitors enhances tumor suppression and inhibition of cell cycle-related gene expression [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 P2-24-07.
Abstract P2-26-13: Gene deletion of insulin receptor in MCF-7L breast cancer cells by CRISPR gene editing
Authors: Zhang Xihong , Monteiro Marvis , Yee Douglas 
Published: March 2023

Abstract
The type I insulin-like Growth Factor Receptor (IGF-IR) plays important roles in breast cancer cell proliferation and metastasis. However, preclinical and clinical research targeting IGF-IR also revealed the potential for insulin receptor (IR) to compensate for IGF-1R inhibition. IR is expressed as two isoforms (IRA and IRB) through alternative splicing. The IRB is expressed in adult tissues and thought responsible for cell metabolism while IRA is expressed in fetal development to enhance cell growth. Since breast cancer cells usually express both IGF-IR and IRA/IRB, differential signaling by IRA and IRB has not been clearly demonstrated. To further define the role for IR, we used CRISPR technology for gene editing in exon 2 of IR in MCF-7L cells to delete IR. Cells were selected for absent IR expression by flow cytometry and Sanger sequencing confirmed that one of the clones (CL35) had the targeted 4 base pair deletions in exon 2. Immunoblotting using an antibody to the  subunit of IR showed no expression in CL35. Unexpectedly, 10 nM insulin exposure resulted in downstream AKT and Erk1,2 phosphorylation. Immunoprecipitation showed that IGF-IR was activated by the insulin in CL35 cells. Insulin signaling in CL35 through IGF-IR was inhibited by huEM164, an anti IGF-IR monoclonal antibody. Compared to MCF-7L parental cells, CL35 was more sensitive to IGF-I and less sensitive to insulin as demonstrated by downstream AKT phosphorylation and MTT monolayer growth assay. Insulin stimulated monolayer growth of CL35 measured by MTT was not affected in testing serum free media (SFM) unless transferrin was deleted from the media. These data suggest IGF-IR can function to activate signaling in response to insulin. To ensure that our clone does not contain alternate splicing products resulting in aberrant IR proteins, we are further sequencing IR mRNA in CL35. In conclusion, we have established an IR null breast cancer cell line with reduced sensitivity to insulin and increased sensitivity to IGF-I. This cell line can be used to express the IRA and IRB isoforms to characterize their function in breast cancer cells.
Citation Format: Xihong Zhang, Marvis Monteiro, Douglas Yee. Gene deletion of insulin receptor in MCF-7L breast cancer cells by CRISPR gene editing [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 P2-26-13.
Abstract P3-03-03: Risk factors associated with chemotherapy-induced nausea and vomiting among breast cancer patients receiving highly emetogenic chemotherapy
Authors: Yeo Winnie , Ngai Nicole , Yip Christopher , Yeo Victoria , Ko Jonathan , Yip Claudia , Mo Frankie 
Published: March 2023

Abstract
Purpose: Although risk factors related to chemotherapy-induced nausea and vomiting (CINV) have been identified by prior studies, there are only few studies evaluating risk factors associated with the contemporary antiemetic prophylaxis, including that of olanzapine/aprepitant- or NEPA- containing regimens. The present study aimed to identify the risk factors related to CINV development in Chinese breast cancer patients receiving doxorubicin and cyclophosphamide chemotherapy. Methods: Data from 304 patients who were enrolled to 3 previously reported prospective antiemetic studies were included. Multivariate logistic regression models were used to predict risk factors associated with the occurrence of CINV. Additionally, likelihood of treatment failure in relation to number of risk factors of individual patient was evaluated. Results: Multivariate analysis of the entire study group revealed that obese status (defined as body mass index &gt;/= 25.0 kg/m2) and the use of olanzapine/aprepitant- or NEPA- containing antiemetic regimens were associated with high likelihood, while history of motion sickness was associated with lower likelihood, of complete response (CR) and ‘no nausea’ in the overall phase. History of vomiting in pregnancy was also associated with lower likelihood of overall CR. Patients with increasing number of risk factors had higher likelihood of treatment failure as well as shorter time to first vomiting. Those who did not achieve CR and ‘no nausea’ in the first cycle were less likely to achieve these parameters in the subsequent cycle of chemotherapy. Conclusions: This present study confirmed the previously reported risk factors to be important for CINV in Chinese breast cancer patients receiving doxorubicin and cyclophosphamide. Further optimization of CINV control is required for patients with identifiable risk factors; olanzapine/aprepitant- or NEPA- containing prophylaxes are the preferred contemporary antiemetics regimens for Chinese breast cancer patients undergoing doxorubicin and cyclophosphamide chemotherapy.
Citation Format: Winnie Yeo, Nicole Ngai, Christopher Yip, Victoria Yeo, Jonathan Ko, Claudia Yip, Frankie Mo. Risk factors associated with chemotherapy-induced nausea and vomiting among breast cancer patients receiving highly emetogenic chemotherapy [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 P3-03-03.
Abstract P3-03-15: Physical Activity and Risk of Death in Breast Cancer Survivors: A Prospective Study
Authors: Chen Lie Hong , Irwin Michael R. , Olmstead Richard , Haque Reina 
Published: March 2023

Abstract
BACKGROUND. Strong evidence exists supporting the protective effect of physical activity on the risk of developing breast cancer; however, its impact on survival after breast cancer diagnosis remains controversial with limited research in long-term survivors. The aim of the current study was to evaluate the association of physical activity and risk of all-cause mortality in long-term breast cancer survivors.
METHODS. We conducted a prospective cohort of 315 post-menopausal breast cancer survivors who were at least 2 years post their initial diagnosis (median 6 years of survivorship). They initially were diagnosed with early stage (AJCC TNM Stages 0-II) breast cancer between January 1996-December 2012. Baseline interviews were conducted between August 2013 and March 2015, and participants were followed until date of death or study’s end (April 2022). Subjects were queried on physical activity and fatigue using validated questionnaires, Godin Leisure Physical Activity Scale (GLPAS) and Fatigue Symptom Inventory (FSI). Physical activity was defined in 3 levels (active, moderately active, insufficiently active). Cox proportional hazards regression model was used to estimate the association of physical activity with risk of all-cause mortality, adjusted for age at baseline, breast cancer stage, Charlson comorbidity index (CCI), years since cancer diagnosis, fatigue, race/ethnicity, lifetime history of insomnia and depression, and adjuvant cancer treatments (endocrine, chemotherapy and radiation).
RESULTS. Of the 315 women, mean age at interview was 71 years (range: 57-86). The cohort included 30% women of color, mainly African American/Black and Asian/Pacific Islander women. Over a maximum follow-up of 8.7 years (median:7.8, IQR:7.3-8.3) after their baseline interview, 45 subjects (14.3%) died due to all causes. The mortality rates were: 12.9 per 1000 person years (PY) for active; 13.4 per 1000 PY for moderately active; and 32.9 per 1000 PY for insufficiently active. In multivariable analysis, compared to insufficiently active women, those who were active or moderately active had a markedly 60% decreased risk of death (active: HR=0.42, 95% CI: 0.21-0.85; moderately active: HR=0.40, 95% CI:0.17-0.95).
CONCLUSION: We found that even moderate physical activity was associated with a significantly decreased risk of all-cause death in long-term breast cancer survivors. Survivorship care plans should consider incorporating physical activity because even moderate activity is vital for extending survival as well as health-related quality of life.

Citation Format: Lie Hong Chen, Michael R. Irwin, Richard Olmstead, Reina Haque. Physical Activity and Risk of Death in Breast Cancer Survivors: A Prospective Study [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 P3-03-15.
Abstract P3-07-01: Mebendazole displays selective anti-breast cancer cytotoxicity via the induction of mitotic catastrophe
Authors: Yan Ying , Baranowska-Kortylewicz Janina , Graff Brendan 
Published: March 2023

Abstract
Metastatic breast cancer (mBC) is still an incurable disease and is responsible for the majority of breast cancer-related death, despite tremendous efforts spent on developing better regimens for mBC. Microtubule-targeting chemotherapy agents (MTAs) have been on the front lines of treating mBC. However, many of these drugs become ineffective following treatment, as a consequence of either primary or acquired resistance, which leads to refractory disease. Furthermore, failures of the first-line MTA treatment will negatively affect the effectiveness of the second- and third-line agents in the patients, as the overall response rates of the subsequent treatments are in a range of only ~12% to 35%. Thus, there is an urgent need for alternative MTAs that are significantly different in biological characteristics from those currently used MTAs for mBC therapy. For this purpose, we investigated Mebendazole (methyl 5-benzoyl-2-benzimidazole-carbamate (MEB), which binds different sites on the α/β-tubulin remote from the binding sites of other MTAs, for its potential against mBC cells. MEB has much lower in vivo toxicity than the other MTAs used to treat mBC and it can be orally administrated. We explored MEB for its effectiveness in anti-mBC cells with a panel of human breast normal and mBC cell lines. The data from clonogenic survival studies indicate that MEB delivers &lt; 10-fold greater cytotoxicity toward mBC cells compared to normal mammary epithelial (HME) or benign breast tumor cells. Furthermore, the cytotoxicity in detected in mBC cells was attributed to the induction of mitotic catastrophe, as demonstrated by the increased mitotic cell population (cells with 4N-DNA content and Histon-H3-Ser10 phosphorylation) and concurrent nuclear fragmentation. In contrast, under the same dose range, MEB did not cause mitotic catastrophe in HME cells. In addition, our data also show that MEB is much more efficient in killing p53-deficient mBC cells than p53-proficient mBC cells for the same reason, induction of mitotic catastrophe, which suggest the protective function of p53 against MEB-induced mitotic catastrophe. Collectively, our data support a great potential for MEB as an innovative regimen for improving mBC treatment.
Citation Format: Ying Yan, Janina Baranowska-Kortylewicz, Brendan Graff. Mebendazole displays selective anti-breast cancer cytotoxicity via the induction of mitotic catastrophe [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 P3-07-01.