bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract PO3-28-11: Potassium channel activity unveils breast cancer vulnerability
Authors: Gentile Saverio 
Published: May 2024

Abstract
Decades of studies on ion channels have vastly demonstrated the critical functions of these proteins in many physiological and pathological conditions and have provided for an extraordinary pharmacopeia of useful compounds, often with selective actions and minimal side effects. Nevertheless, the function of ion channels in controlling cancer biology is still unknown and underexplored. Our research demonstrates that breast cancer downregulates expression of specific potassium channels (e.g., Kv11.1, KCa3.1) independently of their molecular characterization (ER+, HERB2+ and TNBC). Furthermore, breast cancer patients expressing high protein level of each of these channels presents a better overall survival when compared with patients with low expression. These data indicate that potassium channels can be prognostic factors and that high activity of these protein affects tumor growth. Therefor we wanted to understand the therapeutic benefits of pharmacological targeting specific potassium channels in breast cancer. We discovered that stimulation of the Kv11.1 with specific and selective activator molecules produced a significant growth arrest in a variety of experimental systems including in vitro, in vivo and ex vivo (e.g. Patient-derived organoids) systems. Studying the biochemical pathways that underline these events we discovered that Kv11.1 agonists affects different hallmarks of cancer including metabolism, growth and metastasis signaling without producing significant side effects. For example, use of Kv11.1 agonists produced a strong suppression of oncogene protein function including c-Myc while increasing oncosuppressors such as p21 and p16. These events associated with activation of a senescent phenotype. Furthermore, stimulation of Kv11.1 channel reversed the epithelial-to-mesenchymal transition by inhibiting the WNT signaling and reduced spreading of a TNBC by arresting the metastatic process.. Furthermore, Kv11.1 activation produced a Ca2+-dependent mitochondria damage where the antioxidant transcription factor NRF2 played a fundamental role in determining resistance to death. Therefore, we conclude that targeting the Kv11.1 potassium channel in breasts cancer can be considered a new, effective and safe targeting strategy for breast cancer.
Citation Format: Saverio Gentile. Potassium channel activity unveils breast cancer vulnerability [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-28-11.
Abstract PO4-05-10: A Carryover Effect: Antibody Drug Conjugates Constantly Provide a Substantial Improvement in Overall Survival more than in Progression-free Survival
Authors: Chen I-Chun , Lin Ching-Hung , Lu Yen-Shen 
Published: May 2024

Abstract
Background: In metastatic breast cancer (MBC), progression-free survival (PFS) improvement does not always translate into overall survival (OS) benefit. Multiple treatment options after progression resulted in a long post-progression survival in MBC patients, and these would make the dissociation of PFS benefit and OS benefit. We have reported the constant correlation of PFS improvement and OS improvement in anti-HER2 containing treatment (Breast 2021; 59:211-220). The relationship between PFS and OS improvement in antibody drug conjugate has not been thoroughly examined.
Methods: “Metastatic breast cancer” and “antibody drug conjugate” (ADC) were used as keywords to search for randomized clinical trials that report both PFS and OS. Hazard ratios (HR) and median survival were analyzed. Increments in PFS (delta PFS) and increments in OS (delta OS) were compared between studies.
Results: A total of 8 trials were identified and summarized in table 1. The target of ADC was HER2 (N=6) or Trop2 (N=2). In DESTINY-Breast 03 trial, the control arm was another ADC (T-DM1). The control arms in all the other 7 trials were chemotherapy. The HR of PFS (range 0.28-0.66) was smaller than HR of OS (range 0.48- 0.83) in all of the trials. The median OS was not reached (NR) in 1 of the trials (DB-03) and was thus removed from the analysis for delta PFS and delta OS. In the comparison of delta PFS, the increments of median PFS fell between 1.5 and 10.9 months(m). The increments of median OS were between 1.6 and 12.7 m. All the delta OS are greater than the delta PFS in the 7 trials with available PFS and OS data.
Conclusion: In MBC, ADCs targeting HER2 and Trop2 both constantly provide improvement of OS greater than PFS. Further investigation on the potential mechanism is warranted.
Table 1
Citation Format: I-Chun Chen, Ching-Hung Lin, Yen-Shen Lu. A Carryover Effect: Antibody Drug Conjugates Constantly Provide a Substantial Improvement in Overall Survival more than in Progression-free Survival [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-05-10.
Abstract PO4-10-08: Building a standard methodology: Early Gynecologic Consultation and Bone Mass Density Examination in Breast Cancer Patients Receiving Endocrine Therapy
Authors: Ching-Wen Chiu , Ka-Wai Tam , Chih-Ming Su , Hsueh-Chi Wu 
Published: May 2024

Abstract
Purpose
Hormone receptor-positive type of breast cancer is typically treated with hormone therapy (HT), including tamoxifen and aromatase inhibitors (AI). However, long-term use of HT may increase the risks of endometrial cancer, vaginal dryness, and osteoporosis. To minimize the risks, breast surgeons should schedule regular follow-up with gynecologists and arrange bone mass density (BMD) examination. Using the Plan-Do-Study-Act (PDSA) methodology, we aimed to increase cross-team care with gynecology department and to promote BMD examination for breast cancer patients receiving HT.
Methods
We formed a multidisciplinary team including breast surgery department and gynecologic department in our hospital that care for female patients with breast cancer and related side effects. We arranged a lecture for all collaborative doctors, introducing our aims, interventions, and measurement strategies to test in multiple PDSA cycles. The interventions with standardized criteria include: (1) a gynecologic consultation, triggered if a patient initially receive tamoxifen and (2) a BMD examination, triggered if a patient initially receive AI. The triggering mechanism is embedded in the ambulatory alarming system. Both the intervention rates were tracked during PDSA cycle 1 in 2023 and compared with baseline rates in 2020-2022. Adherence to the plan was maintained and measured using data analytic reports and chart audits.
Results
The gynecologic consultation rate during PDSA cycle 1 is significantly higher than the baseline, which is 40.4% and 22.4% (p = 0.006), respectively. In patients who received tamoxifen, 6-month-consultation rate during PDSA cycle 1 is also significantly higher than the baseline group, which is 77.77% and 42.9% (p = 0.005), respectively. The median time from HT therapy to first gynecologic consultation decreased from 51 days to 28 days. Furthermore, the baseline BMD testing rate before our intervention was 30.6%. This increased to 48.3% during PDSA cycle 1.
Conclusion
Standardized gynecologic consultation criteria led to earlier gynecologic consultation in breast cancer patients receiving tamoxifen and higher BMD test rates in patients receiving AI. Future PDSA cycles will focus on assessing the frequency of subsequent gynecologic encounters in patients who received a triggered gynecologic consult.
Citation Format: Chiu Ching-Wen, Tam Ka-Wai, Su Chih-Ming, Wu Hsueh-Chi. Building a standard methodology: Early Gynecologic Consultation and Bone Mass Density Examination in Breast Cancer Patients Receiving Endocrine Therapy [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-10-08.
Abstract PO4-13-01: A randomised trial comparing 6-monthly dosing of adjuvant zoledronate with a single one-time dose in patients with early breast cancer (REaCT-ZOL): Quality of life and toxicity outcomes
Authors: Machado Igor , Clemons Lucas , Stober Carol , Pond Gregory , Awan Arif , Conter Henry , Simos Demetrios , Dhesy-Thind Sukhbinder , Mates Mihaela , Kumar Vikaash , Hilton John , Vandermeer Lisa , Clemons Mark 
Published: May 2024

Abstract
Background: While adjuvant 6-monthly zoledronate is widely used in patients with early-stage breast cancer (EBC), questions remain around optimal scheduling of adjuvant bisphosphonates. We reviewed quality of life and bisphosphonate-related toxicities observed within a prospective randomised trial.
Methods: Patients with EBC were randomised to either a single infusion of adjuvant zoledronate (4mg IV) or to 6-monthly treatment for 3 years. Quality of life was measured using the EQ-5D-5L questionnaire (before and after each infusion and 6-monthly thereafter in the single infusion arm). Acute phase reaction (APRs) data was collected after each infusion and data on other bisphosphonate-related toxicities (hypocalcaemia, renal impairment, ONJ and atypical fractures) was collected 6-monthly for 3 years.
Results: Between 21-Nov-2018 and 02-Apr-2020, 211 patients were randomized to either a single infusion (n=107) or 6-monthly (n=104) adjuvant zoledronate. While each zoledronate infusion was associated with a worsening QoL, the overall QoL was the same in the two study arms. APRs occurred in 75% of patients after receiving zoledronate. Other bisphosphonate-related toxicities were uncommon in either arm. Significantly more patients discontinued study treatment in the 6-monthly arm (30/104, 28.8%) compared with the single infusion arm (3/107, 2.8%) (p &lt; 0.001). The most common reason for study discontinuation was the occurrence of APRs, pain and malaise. Disease-free and overall survival rates were not significantly different in the study arms.
Discussion: A single infusion of adjuvant zoledronate may offer patients a more convenient and better tolerate regimen than repeat infusions. APRs remain an important toxicity with repeat infusions of zoledronate, leading to increased rates of treatment discontinuation. Larger, definitive, trials comparing a single infusion with repeat treatments are required.
Citation Format: Igor Machado, Lucas Clemons, Carol Stober, Gregory Pond, Arif Awan, Henry Conter, Demetrios Simos, Sukhbinder Dhesy-Thind, Mihaela Mates, Vikaash Kumar, John Hilton, Lisa Vandermeer, Mark Clemons. A randomised trial comparing 6-monthly dosing of adjuvant zoledronate with a single one-time dose in patients with early breast cancer (REaCT-ZOL): Quality of life and toxicity outcomes [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-13-01.
Abstract PO4-17-09: Epidemiological Analysis and Overall Survival of Male Breast Cancer in a Developing Middle Eastern Country Over 18 Years
Authors: Abdulelah Zaid , Abdulelah Ahmed , Alhajahjeh Abdulrahman , Ghazzawi Ahmad , El-Amayreh Layla , Abdel-Razeq Hikmat 
Published: May 2024

Abstract
Background: despite the profound rarity of breast cancer in males, it remains of importance given the associated morbidity and mortality, including the association with worse prognosis than female patients. Nonetheless, male breast cancer epidemiology remains poorly studied in middle eastern populations.
Methodology: This retrospective cohort study examined male patients aged 15 to 85 years who were diagnosed with breast cancer between 2000 and 2018, using data from the Jordan Cancer Registry. Kaplan-Meier analysis was performed to assess the 5-year overall survival of the patients over time.
Results: A total of 22,600 patients were diagnosed with breast cancer since 2000 in Jordan, of which 362 (1.6%) patients were males. 39.8% of male breast cancer cases occurred in the right breast, while the left breast was affected in 43.4% of the cases, and 3.3% of the cases were bilateral. Meanwhile, laterality was not mentioned in 13.5% of registry records.
All male breast cancer cases were malignant in origin with the breast being the primary cancer. Most male patients had grade II (N=112, 30.9%) followed by grade III breast cancer (N=88, 24.3%).
Among the male breast cancer cohort, 224 (62.2%) were treated with surgical intervention, 103 (28.8%) patients were given chemotherapy, 84 (23.4%) patients had radiotherapy and 24 (6.70%) patients had hormonal therapy.
27 patients died during the follow up period. The 5-year overall survival rate for the patients was 92.5% (95% CI, 89.9% to 95.3%).
Conclusion: Breast cancer in middle eastern males tends to more commonly present in the left breast, and at a more advanced stage in comparison to females.
Citation Format: Zaid Abdulelah, Ahmed Abdulelah, Abdulrahman Alhajahjeh, Ahmad Ghazzawi, Layla El-Amayreh, Hikmat Abdel-Razeq. Epidemiological Analysis and Overall Survival of Male Breast Cancer in a Developing Middle Eastern Country Over 18 Years [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-17-09.
Abstract PO4-17-10: Epidemiological Analysis and Overall Survival of Female Adolescent and Young Adults Breast Cancer in a Developing Middle Eastern Country Over 18 Years
Authors: Abdulelah Ahmed , Abdulelah Zaid , Alhajahjeh Abdulrahman , Ghazzawi Ahmad , El-Amayreh Layla , Abdel-Razeq Hikmat 
Published: May 2024

Abstract
Background: Breast cancer is the most common type of cancer among female adolescents and young adults (AYAs) aged 15-39 years at diagnosis. AYAs with breast cancer have worse prognosis and are more likely to present with unfavorable tumor biology. However, breast cancer in AYAs is still poorly reported in middle eastern populations.
Methodology: This is a retrospective cohort study which examined female AYAs patients aged 15 to 39 years at the time of diagnosis who were diagnosed with breast cancer between 2000 and 2018, using data from the Jordan Cancer Registry. Kaplan-Meier analysis was performed to assess the 5-year overall survival of the patients over time.
Results: A total of 3831 Female AYAs were diagnosed with breast cancer in Jordan between 2000 and 2018 with a median age of 34.2 (IQR 30.9-38.3) years. 43.2% of female AYAs breast cancer cases were right breast cancer, whereas left breast cancer occurred in 47.4% of cases, and only 2.15% of cases were bilateral breast cancer. Meanwhile, 7.31% of cases did not have a reported laterality in the registry records.
Most female AYAs patients had high grade breast cancer with grade III breast cancer being the most common (N=1349, 35.2%) followed by grade II breast cancer (N=1093, 28.5%).
Among this female AYA cohort, 2208 (59.3%) were treated with surgical intervention, 1621 (43.5%) patients were given chemotherapy, 1220 (32.7%) patients had radiotherapy, 265 (7.15%) patients had hormonal therapy and only 47 (1.27%) were treated with immunotherapy.
Among the entire studied cohort, 229 (5.98%) patients died during follow up period. The 5-year overall survival was 94% (95% CI 93.3% to 94.8%)
Conclusion: Female AYAs breast cancer tends to have a predilection towards the left breast, but presents at a more advanced grade compared with other age groups in females.
Citation Format: Ahmed Abdulelah, Zaid Abdulelah, Abdulrahman Alhajahjeh, Ahmad Ghazzawi, Layla El-Amayreh, Hikmat Abdel-Razeq. Epidemiological Analysis and Overall Survival of Female Adolescent and Young Adults Breast Cancer in a Developing Middle Eastern Country Over 18 Years [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-17-10.
Abstract PO4-22-04: Evaluation of acute toxicity in breast cancer patients receiving concurrent capecitabine and radiation
Authors: Shalaby Ahmed , Sherwani Zohaib , Hathout Lara , Jan Imraan , Haffty Bruce , George Mridula , Kumar Shicha , Omene Coral , Toppmeyer Deborah , Ohri Nisha 
Published: May 2024

Abstract
Purpose: Adjuvant capecitabine has been shown to improve disease-free survival and overall survival in breast cancer patients who have residual disease after neoadjuvant chemotherapy, particularly in those with triple negative breast cancer (TNBC). While adjuvant chemotherapy is often completed prior to adjuvant radiotherapy (RT), capecitabine may be administered concurrent with RT to reduce the time from surgery to RT. The purpose of this study was to evaluate the feasibility of concurrent therapy and the associated rates of acute loco-regional toxicity.
Materials and Methods: A retrospective chart review was performed to identify all breast cancer patients who received adjuvant capecitabine and RT. Patients with a history of prior RT, patients who were treated with capecitabine and RT sequentially, and patients who were treated with palliative intent were excluded. Capecitabine was given Monday-Friday during RT. Patient and disease characteristics, capecitabine and RT treatment details, acute toxicity, and treatment breaks were recorded. Toxicity was scored by the Common Terminology Criteria for Adverse Events (CTCAE) version 5.
Results: A total of 27 patients with non-metastatic breast cancer who received concurrent capecitabine and RT with definitive intent treated from 2013 to 2023 were identified. Median age at diagnosis was 52 years [Interquartile Range (IQR) 40-60]. Adjuvant capecitabine dose ranged from 500-1500 mg twice daily. Adjuvant RT dose ranged from 42.56 Gray (Gy) to 50.4Gy. The majority of patients (92.6%) received a sequential 10-14 Gy boost to the lumpectomy site or mastectomy scar, and 70.3% of patients received elective regional nodal RT. During treatment, all patients developed Grade 1 or 2 radiation dermatitis, while Grade 3 radiation dermatitis was noted in 4 (14.8%) patients. Two patients required a treatment break from RT, and both patients were able to subsequently complete their planned RT course. Seven patients (25.9%) required a capecitabine dose reduction or capecitabine treatment break during RT. No Grade 4 or 5 toxicities were reported. Median follow-up from RT completion was 7 months [IQR 0.98-12.2]. At last follow-up, radiation dermatitis had improved to Grade 0-1 for all patients.
Conclusion: Concurrent adjuvant capecitabine and RT is a feasible treatment approach that is well tolerated with acceptable acute toxicities.
Citation Format: Ahmed Shalaby, Zohaib Sherwani, Lara Hathout, Imraan Jan, Bruce Haffty, Mridula George, Shicha Kumar, Coral Omene, Deborah Toppmeyer, Nisha Ohri. Evaluation of acute toxicity in breast cancer patients receiving concurrent capecitabine and radiation [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-22-04.
Abstract PO4-23-03: The Influence of Reconstruction Type on Outcomes in Women Undergoing Mastectomy with Immediate Reconstruction: A Nationwide Study
Authors: Hernandez Lucia Castro , Parreco Joshua 
Published: May 2024

Abstract
INTRODUCTION:
Outcomes after mastectomy with immediate reconstruction may vary depending on the type of reconstruction, but the evidence is limited and inconsistent. The purpose of this study was to compare the most common reconstruction techniques in a large national cohort of women undergoing these procedures.
METHODS:
The Nationwide Readmissions Database for 2016-2020 was queried for all women aged 18 years or older undergoing mastectomy for breast cancer with immediate reconstruction. The primary outcome was prolonged length of stay (LOS) greater than 7 days. The secondary outcomes were readmission within 30 days and readmission to a different hospital. The types of reconstruction were compared along with all other relevant variables from the database. Univariable comparison was performed using chi-squared tests for each outcome. Multivariable logistic regression was performed using all significant confounders.
RESULTS:
During the study period, 35,430 patients were identified undergoing mastectomy for breast cancer with immediate reconstruction. The rate of prolonged (LOS) was 2.4% (n= 840) and the readmission rate was 5.4% (n=1,919). From the readmitted patients, the rate of readmission to a different hospital was 14.2% (n=273). Controlling for confounders with multivariable logistic regression revealed the strongest risk factors for prolonged LOS were latissimus dorsi flap (OR 5.4 [4.0-7.4] p&lt; 0.001) and an investor-owned hospital (OR 4.3 [3.5-5.2] p&lt; 0.001). The highest risk of readmission was a transverse rectus abdominis flap (OR 1.3 [1.1-1.6] p&lt; 0.001) and the highest risk of readmission to a different hospital was a small hospital (OR 2.2 [1.6-3.1] p&lt; 0.001).
CONCLUSION:
Reconstruction type influences outcomes in women undergoing mastectomy. These outcomes have significant implications for surgical decision-making and fragmentation of care. Further research to identify ways to reduce adverse outcomes and improve patient satisfaction is warranted.
Citation Format: Lucia Castro Hernandez, Joshua Parreco. The Influence of Reconstruction Type on Outcomes in Women Undergoing Mastectomy with Immediate Reconstruction: A Nationwide Study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-23-03.
Abstract PO4-25-05: LYVE-1 expressing macrophages modulate the extracellular matrix and contribute to mammary tumor growth
Authors: Elfstrum Alexis , Rumahorbo Annisa , McCluskey Braedan , Nelson Emma , Schwertfeger Kaylee 
Published: May 2024

Abstract
Macrophages represent a heterogeneous myeloid population with varied functions in normal tissue and tumors. We identify a tissue resident macrophage subpopulation marked by the protein LYVE-1 in both the female mammary gland and mammary tumor. In a genetic LYVE-1+ macrophage deletion model, loss of LYVE-1+ macrophage leads to accumulation of the extracellular matrix glycosaminoglycan hyaluronan. Further, qRT-PCR of tissue lacking LYVE-1+ macrophages yields a gene signature associated with extracellular matrix disorganization. Supporting a tissue remodeling functionality, inducing a LYVE-1 macrophages phenotype in vitro prompts HA internalization and increases hyaluronidase expression. In a murine tumor model, deletion of LYVE-1+ macrophages slows tumor progression and increases HA accumulation, suggesting an anti-tumorigenic, tissue remodeling phenotype. LYVE-1+ macrophages preferentially localize to HA dense regions of tumors, specifically in the tumor stroma, while scRNA-seq of murine tumors demonstrates a LYVE-1+ macrophage phenotype associated with tissue remodeling and immunosuppression. Our data illustrate a LYVE-1+ macrophage population critical for HA homeostasis and tumor progression.
Citation Format: Alexis Elfstrum, Annisa Rumahorbo, Braedan McCluskey, Emma Nelson, Kaylee Schwertfeger. LYVE-1 expressing macrophages modulate the extracellular matrix and contribute to mammary tumor growth [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-25-05.