bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract PO5-12-08: QTc prolongation as Adverse Effect of CDK4/6 inhibitors: A systematic review and meta-analysis of randomized controlled trials
Authors: Carvalho Bruno , Reis Pedro Cotta Abrahão , Marinho Alice , Comini Ana Carolina , Xavier Debora , Pessoa Beatriz Mella S. , Batalini Felipe 
Published: May 2024

Abstract
Introduction: CDK4/6 inhibitors (CDK4/6i), such as abemaciclib, ribociclib, and palbociclib, have significantly improved outcomes for patients with ER+/HER2− breast cancer. Nevertheless, they differ among each other in terms of chemical, biological, and pharmacological features, as well as toxicity profiles. Ribociclib causes concentration-dependent increases in the QTc interval, particularly in combination with tamoxifen. However, the pathogenesis of ribociclib-induced QTc prolongation remains unclear. We aim to determine whether QTc prolongation is caused by CDK4/6i in general or if it is associated with ribociclib only.
Methods: We performed a systematic review and meta-analysis of randomized clinical trials (RCTs) to compare QTc prolongation in patients using CDK4/6i in combination with hormonal agents to patients that did not use CDK4/6i, including neoadjuvant, adjuvant, or metastatic scenarios in breast cancer. We searched Embase, PubMed and Cochrane Library databases from inception to June 2023. The outcomes evaluated were QTc prolongation of all grades. Statistical analysis was performed with R software version 2023.03.0+386.
Results: We included 14 RCTs comprising 16,013 patients in the quantitative analysis, of whom 8,585 underwent therapy with CDK4/6i, and one more paper was included only in the qualitative analysis due to not reporting the exact number of events of QTc prolongation. An increased risk of QTc prolongation was associated with the use of CDK4/6i (RR 2.32; 95% CI 1.67–3.23; p=0.000001; I²=46%). Subgroup analyses revealed a significant increase in the QTc interval for the ribociclib and palbociclib cohorts. The ribociclib subgroup showed a risk ratio of 3.07 (RR 3.07; 95% CI 2.17-4.36; p&lt; 0.000001; I² = 21%) while the palbociclib subgroup had a risk ratio of 1.52 (RR 1.51; 95% CI 1.05-2.16; p=0.025, I²=0%).
Conclusion: Our findings suggest that QTc prolongation may be a common adverse effect of CDK4/6i, with ribociclib carrying greater risk. These results are important for guiding clinical decision-making, and further investigation is warranted to better understand the mechanisms and clinical implications of CDK4/6 i-induced QTc prolongation.
Citation Format: Bruno Carvalho, Pedro Cotta Abrahão Reis, Alice Marinho, Ana Carolina Comini, Debora Xavier, Beatriz Mella S. Pessoa, Felipe Batalini. QTc prolongation as Adverse Effect of CDK4/6 inhibitors: A systematic review and meta-analysis of randomized controlled trials [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 PO5-12-08.
Abstract PO5-16-06: Prophylactic Neurokinin-1 Receptor Antagonist Use Pre- and Post- Choosing Wisely Initiative among Women with Breast Cancer
Authors: Kamat Shweta , Brown Britny , Cohen Steven , Vyas Ami 
Published: May 2024

Abstract
Objective: In April 2012, the American Society of Clinical Oncology (ASCO) issued recommendations as a part of the Choosing Wisely (CW) campaign with the aim to identify the areas of low-value utilization. One of the CW recommendations is not to use expensive antiemetics, specifically Neurokinin-1 Receptor Antagonist (NK1-RA) for patients initiating low or moderate emetic risk chemotherapy. The purpose of this study was to determine the impact of CW on prophylactic NK1-RA use among women with breast cancer.
Methods: Using Optum’s de-identified Clinformatics® Data Mart Database for 2010 to 2018, a retrospective cohort study was conducted for women aged ≥18 years with breast cancer with at least one newly initiated claim for low/minimal/moderate emetic risk chemotherapy (n = 25,549). All approved antiemetics - aprepitant, fosaprepitant, rolapitant, and netupitant/palonosetron) were included. An interrupted time series using a segmented regression model was used to assess the effect of CW on the prophylactic NK1-RA use.
Results: The prophylactic use of NK1-RAs among patients with breast cancer receiving low/minimal/moderate emetic risk chemotherapy decreased from 11.1% pre-CW to 7.7% post-CW. Segmented regression analysis showed that there was a significant increase of 0.11 per 100 patients per quarter in the use of prophylactic NK1-RAs prior to CW recommendation. However, immediately after the CW (occurred in Q42013), there was a significant decline in prophylactic NK1-RA use by 1.03 per 100 patients in Q22014. For the time after intervention, there was a significant decline in NK1-RA use by 0.37 per 100 patients per quarter in the post-CW period compared to the pre-CW period (p&lt; 0.05).
Conclusion: This study highlights a significant but modest decline in the inappropriate use of prophylactic NK1-RAs after the implementation of CW antiemetic recommendation. Continued statewide or local educational efforts for dissemination of CW recommendations are needed to facilitate appropriate prophylactic use of NK1-RAs.
Table. Adjusted* Interrupted Time Series Segmented Regression Analysis of Prophylactic NK1-RA use among women with breast cancer before and after the Choosing Wisely initiative *Adjusted for insurance, health plan type, age, comorbidity, and emetic risk
Citation Format: Shweta Kamat, Britny Brown, Steven Cohen, Ami Vyas. Prophylactic Neurokinin-1 Receptor Antagonist Use Pre- and Post- Choosing Wisely Initiative among Women with Breast Cancer [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 PO5-16-06.
Abstract PO5-17-02: Triple-negative breast cancer as an untraceable tumor compared to other immunohistochemical subtypes: a cross-sectional study
Authors: Silva Morgana , Nazário Afonso , Sanvido Vanessa 
Published: May 2024

Abstract
Objective: To compare the form of presentation at diagnosis of triple negative breast tumors with other immunohistochemical subtypes, in relation to clinical examination or imaging examination. Methods: This is a cross sectional study that evaluated data related to the presentation of breast carcinomas at diagnosis (clinical examination or screening imaging examination findings), immunohistochemical subtype, histological grade and tumor size, in diagnosed and referred patients. for the Mastology service at Hospital São Paulo – Unifesp, in São Paulo – Brazil, in the period between 2012 and 2021, by analyzing data from the medical records of these patients. Results: Among the 699 invasive carcinomas diagnosed, 246 patients were diagnosed with luminal profile A (35.2%), 257 luminal B (36.8%), 58 luminal B HER-2+ (8.3%), 26 HER-2 enriched (3.7%) and 112 triple negative (16%). Triple negative carcinomas had a higher rate of diagnosis by clinical examination (86.6%), 6.65 times more likely to be diagnosed by clinical examination than luminal A, in addition to having a larger lesion. The triple negative and HER-2 enriched subtypes presented the worst scenarios of clinical stage at diagnosis. Among the tumors diagnosed by screening examination, those belonging to the luminal A were associated with nodules seen on imaging (in 45.1%) and the subtypes luminal B and luminal B HER-2+ with the appearance of microcalcifications. There were no cases of triple negatives involving microcalcifications in our sample. Asymmetries were more common in images of luminal B HER-2+ tumors. In the multivariate analysis, it was observed that only the histological grade and the Ki-67 value are related to the form of diagnosis. Tumors with histological grade 2 or 3 are more likely to be diagnosed by clinical examination and not be traceable in relation to histological grade 1. As for Ki-67, its increase of 1 percentage point leads to an increase of 1.3% in the chance finding on physical examination. There was no correlation of hormone receptors and HER-2 with the chance of the tumor not being screenable. Conclusions: triple negative subtype breast carcinomas present a higher risk of diagnosis by clinical examination compared to other immunohistochemical subtypes and, therefore, tend not to be traceable. Parameters such as high Ki-67 and histological grade correlate with this trend.
Citation Format: Morgana Silva, Afonso Nazário, Vanessa Sanvido. Triple-negative breast cancer as an untraceable tumor compared to other immunohistochemical subtypes: a cross-sectional 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 PO5-17-02.
Abstract PO5-18-06: On-going phase 1A clinical trial of A01, a chimerized monoclonal antibody to Progranulin/Glycoprotein 88 (GP88) in patients with advanced malignancy
Authors: Tkaczuk Katherine , Rosenblatt Paula , Mehra Ranee , Scilla Katherine , Tait Nancy , Yue Binbin , Serrero Ginette 
Published: May 2024

Abstract
Progranulin (PGRN/GP88) is an 88 kDa glycoprotein characterized by seven and a half double cysteine rich repeats which is the largest member of the granulin-epithelin protein family. PGRN/GP88 has been demonstrated as a biological driver of tumorigenesis, survival, and drug resistance in several cancers including breast cancer (BC), lung prostate, ovarian and digestive cancers. PGRN/GP88 tissue expression is an independent prognostic factor of recurrence in breast, lung cancers while elevated serum PGRN/GP88 level in metastatic breast, lung, ovarian and prostate cancer patients. Elevated PGRN/GP88 levels are associated with poor outcomes such as progression and shortened survival. An anti-human PGRN/GP88 monoclonal antibody able to inhibit the the in vitro and in vivo action of human PGRN/GP88 has been developed, chimerized and expressed in CHO cells. All IND enabling activities including pharmacology, GMP manufacturing, formulation and GLP toxicology studies have been conducted. The IND application has been filed and cleared by the Food and Drug Administration. A first-in-human, first-in-class phase 1 safety and efficacy clinical study of AG01 in patients with solid tumors and advanced disease with special focus on patients with breast, lung and ovarian cancers has been initiated and is on-going at the University of Maryland Greenebaum Cancer Center. The trial is registered as NCT05627960 to clinicaltrials.gov site. The presentation will provide an update on the number of patients enrolled in this on-going phase 1A trial.
Supported by grants R44CA162629 and R44CA224718 from the National Cancer Institute to GS.
Citation Format: Katherine Tkaczuk, Paula Rosenblatt, Ranee Mehra, Katherine Scilla, Nancy Tait, Binbin Yue, Ginette Serrero. On-going phase 1A clinical trial of A01, a chimerized monoclonal antibody to Progranulin/Glycoprotein 88 (GP88) in patients with advanced malignancy [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 PO5-18-06.
Abstract PO5-23-02: Targeted Axillary Dissection with Paramagnetic Marker Localization
Authors: Reitsamer Roland , Sir Andreas , Forsthuber Ernst , Peintinger Florentia 
Published: May 2024

Abstract
Background: Targeted axillary dissection (TAD), the combination of sentinel lymph node biopsy (SLNB) and targeted lymph node biopsy (TLNB), can reduce the false negative rates of SLNB alone dramatically in breast cancer patients, who received neoadjuvant chemotherapy (NACT). However optimal methods for TAD are still under investigation. A paramagnetic marker Magseed® was used for the identification of the TLN in this study. Methods: 80 patients eligible to receive NACT were included. All patients had positive axillary lymph nodes verified by core biopsy. Six patients did not receive NACT for any reason. After NACT the targeted lymph nodes (TLNs) were marked with Magseed®, a non-radioactive paramagnetic marker. The SLNs were marked with dual tracer method. The SLNB and the selective TLNB were performed in 74 patients. The Magseed® marked TLNs were identified with the Sentimag® probe and excised. Specimen x-ray was performed to confirm the Magseed® within the prior to NACT biopsied and clipped lymph node. The identification rates of TLNs and SLNs, and the concordance rates were calculated. Results: The TLN identification rate was 100% (74/74), the SLN identification rate was 81.1% (60/74), the concordance rate of TLN and SLN was 58.1% (43/74). In 66.2% (49/74) of the patients the TLN converted to negative, and no ALND was performed. When the TLN converted to negative, a SLN could not be identified in 18.4% (9/49) of the patients. In 33.8% (25/74) of the patients the TLN remained positive after NACT and ALND was performed. When the TLN remained positive, a SLN could not be identified in 40% (10/25) of the patients. Complications according Magseed® deployment or identification could not be observed. Conclusion: Magseed® is a reliable and feasible marker for the identification of TLNs after NACT.
Citation Format: Roland Reitsamer, Andreas Sir, Ernst Forsthuber, Florentia Peintinger. Targeted Axillary Dissection with Paramagnetic Marker Localization [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 PO5-23-02.
Abstract PO5-24-09: Optimizing the Therapeutic Treatment of Breast Cancer Through a Dual Data-driven Theoretical Model
Authors: Najafi A. 
Published: May 2024

Abstract
Despite rapid advancements in treatments and technology, breast cancer remains the second leading cause of cancer related morbidity in women in the US. As a heterogeneous disease, the unique genetic and phenotypic profile of each tumor complicates the prediction of treatment responses and optimized treatment strategies. One primary manifestation of phenotypic plasticity and concomitant intra-tumoral heterogeneity is the Epithelial-Mesenchymal Transition (EMT). The acquisition of migratory and invasive properties through EMT facilitates tumor metastasis and results in worse patient outcomes. As a result, the EMT and its reverse process (MET) often influence treatment response. However, the different mechanisms through which these therapeutic drugs affect the EMT-related phenotypic switching rates as well as each phenotype’s replication rates are unclear, and further investigation is required for better understanding their precise effect for directing optimal treatment strategies and improved patient outcomes. Here, we compile an atlas of publicly available metastatic and non-metastatic RNA sequencing data of breast cancer cell lines treated with therapeutic and chemotherapeutic drugs and propose a dual data-driven theoretical framework for understanding the effects of each drug on breast cancer treatment response. We infer the cell fractions, EMT phenotypic transition rates and phenotypic replication rates of each case through an extension of our previously developed hybrid data-driven and theoretical model, COMET. We infer single-cell RNA sequencing-derived EMT-related trajectories and apply a continuous time Markov chain model to infer inter-state transition rates. By analyzing the atlas of RNA sequencing data and integration with our framework, we gain novel insights into the context-specific mechanisms by which therapeutic drugs affect the phenotypic transition rates. This comprehensive understanding will contribute to optimizing breast cancer therapy and ultimately improving patient outcomes.
Citation Format: A. Najafi. Optimizing the Therapeutic Treatment of Breast Cancer Through a Dual Data-driven Theoretical Model [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 PO5-24-09.
Abstract PO5-25-05: Crosstalk between adipocyte and tumor cells with ESR1 mutations via adipsin enhances tumor growth
Authors: Belyakov Artem , Jin Kideok 
Published: May 2024

Abstract
While endocrine therapies have shown clinical benefits for breast cancer with ESR1 mutations, resistance development is a significant challenge. Evidence suggests that the complement system is critical to tumor development, and recent studies highlight the role of adipsin in breast cancer growth. In a previous study, we characterized the role of complement pathway-mediated adipsin in ESR1 mutant cell lines (Y537S and D538G), identifying the upregulation of adipsin, C3, and C3aR in ESR1 mutant cells. The interaction between C3a and C3aR enhanced ESR1 mutant cell growth, and inhibiting C3aR abolished cell growth and increased apoptosis. Combining C3aR inhibitors with fulvestrant or CDK4/6 inhibitors had a synergistic inhibitory effect on ESR1 mutant cells. Our findings suggest that the complement pathway plays a role in ESR1 mutant cell proliferation and that C3aR is a potential target to mitigate ESR1 mutant breast cancer growth and metastasis. Additionally, we demonstrated the critical role of the feedback loop of adipsin in ESR1 mutant cell growth in adipocyte crosstalk. Using differentiated mouse 3T3-L1 adipocytes induced with tumor-conditioned media from ESR1 mutant cells, we observed the upregulation of adipsin, C3, and C3a in the adipocyte secretome, which enhanced C3a levels. Blocking the interaction between C3a and C3aR in ESR1 mutant cells using a C3aR inhibitor significantly inhibited ESR1 mutant cell growth compared to wild-type cells and enhanced apoptosis. Our findings suggest that upregulation of adipsin from ESR1 mutant cells and adipocytes in crosstalk increases tumor cell growth. Future studies will investigate the critical role of adipsin's auto- and paracrine effects in breast cancer with ESR1 mutations.
Citation Format: Artem Belyakov, Kideok Jin. Crosstalk between adipocyte and tumor cells with ESR1 mutations via adipsin enhances 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 PO5-25-05.
Abstract PO5-27-03: Mutational impact of APOBEC3A and APOBEC3B in a human cell line
Authors: Carpenter Michael , Temiz Nuri , Ibrahim Mahmoud , Jarvis Matthew , Brown Margaret , Argyris Prokopios , Brown William , Yee Douglas , Harris Reuben 
Published: May 2024

Abstract
A major source of mutation in cancer is DNA cytosine deamination by APOBEC3 enzymes resulting in C-to-T and C-to-G mutations in TCA and TCT motifs. Here, we develop a selectable system to quantify genomic mutations and compare the mutagenic activities of three leading APOBEC3 candidates - APOBEC3A, APOBEC3B, and APOBEC3H. The human cell line, HAP1, is engineered to express the thymidine kinase (TK) gene of HSV-1, which confers sensitivity to ganciclovir. Expression of APOBEC3A and APOBEC3B, but not catalytic mutant controls or APOBEC3H, triggers increased frequencies of TK mutation and nearly indistinguishable TC-biased cytosine mutation profiles in the selectable TK reporter gene. Whole genome sequences from TK mutant clones enabled an analysis of thousands of single base substitution mutations and extraction of local sequence preferences with APOBEC3A preferring YTCW motifs over 70% of the time and APOBEC3B just under 50% of the time (Y=C/T; W=A/T). Signature comparisons with breast tumor whole genome sequences indicate that most malignancies manifest intermediate percentages of APOBEC3 signature mutations in YTCW motifs, mostly between 50 and 70%, suggesting that both enzymes are contributing in a combinatorial manner to the overall mutation landscape. These studies combine to help resolve a long-standing etiologic debate on the source of APOBEC3 signature mutations in cancer and indicate that future diagnostic and therapeutic efforts should focus on both enzymes.
Citation Format: Michael Carpenter, Nuri Temiz, Mahmoud Ibrahim, Matthew Jarvis, Margaret Brown, Prokopios Argyris, William Brown, Douglas Yee, Reuben Harris. Mutational impact of APOBEC3A and APOBEC3B in a human cell line [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 PO5-27-03.
Abstract PO5-27-08: Cytotoxicity and motility inhibitory effect of FA-Hep-CuS nanoparticles on breast cancer cells
Authors: Arreola David 
Published: May 2024

Abstract
In spite of a decreased rate of cancer onset, by about 33%, since 1991, it is still as dreadful and a major cause of death globally. After heart disease, cancer continues to be the second most prevalent cause of death in the US. According to the American Cancer Society, there will be around 2 million new cases of cancer identified in Americans in 2023, along with approximately 610,000 cancer-related deaths. Breast cancer will continue to be the most common invasive cancer diagnosed in women. Each year about 2.3 million women are diagnosed with breast cancer. In consideration of the severity of breast cancer, herein we designed and synthesized a multimode photothermal agent, FA-Hep-CuS, for the advancement of photothermal therapy of cancer. CuS nanoparticles deposited on heparin-conjugated folic acid (FA-Hep-CuS) were prepared by gently heating unfractionated heparin in dimethyl formamide (DMF), then adding N-(3-dimethylaminopropyl)-N-ethylcarbodiimide hydrochloride (EDC), and finally adding the aminated folic acid in DMF and stirring for four days. Further, FA-Hep was dispersed in DI water, then citrated CuS nanoparticles dispersed in DI water were added, and the mixture was stirred for 8 hours to prepare FA-Hep-CuS. Moreover, the activation of the nanoparticles by non-ionizing radiation (NIR; l= 808 nm) was also evaluated for increased anti-cancer efficiency. In MDA-MB-231 (Triple-negative or TNBC or ER⁻/PR⁻/Her2⁻) breast cancer cell lines, the cytotoxic effects of FA, CuS, and FA-Hep-CuS, as well as their ability to impede motility, have been investigated. They have also been examined to determine how they affect the expression of mesenchymal indicators and clonogenicity. All these demonstrated significant dose-dependent in-vitro cytotoxicity against MDA-MB- 231 breast cancer cells. The cell viability assay showed that the FA-CuS was more effective than FA and CuS. Activation of the nanoparticles with NIR resulted in the significantly enhanced dose-dependent inhibitory potential of the nanoparticles against the migratory properties of the aggressive TNBC cells. In agreement, the clonogenicity of the TNBC cells was also inhibited dose-dependently. We are now focusing on its inhibitory potential on the EMT markers of the TNBC cells. We further aim to investigate the effects of FA-Hep-CuS in in-vivo models of breast cancers.
Citation Format: David Arreola. Cytotoxicity and motility inhibitory effect of FA-Hep-CuS nanoparticles on breast cancer cells [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 PO5-27-08.