tbuckley/cabot-search huggingface dataset:
Abstract PO5-25-09: rs2242652 POLYMORPHISM OF THE hTERT GENE IN WOMEN WITH BREAST CANCER
Authors: Miriam Alvares, Elisa Mascarenhas, Joao Matos
Journal: Cancer Research (2024)

Abstract Introduction: Breast cancer is the most common neoplasm in women around the world. There are several risk factors for this cancer: sex, age, body mass index (BMI), hormone therapy, family history, genetic mutations, among several others. The vast majority of breast tumors are characterized as carcinomas and may originate from ducts or lobules. Immunohistochemistry is related to the expressions of the estrogen receptor (ER) and progesterone receptor (PR), as well as the expression of the human epidermal growth factor receptor 2 (HER2), cell proliferation or the absence of any expression from receptors on the tumor membrane. The telomeres protect the chromosomes natural endings from suffering DNA loss. Telomerase is a ribonuclear protein complex (RNA and protein) that neutralizes telomeres' shortening. Recurrent point mutations in the TERT telomerase promoter have been identified in several cancers, and the rs2242652 polymorphism is a single nucleotide change, and has been described as associated with breast cancer risk. Objective: The objective of this study is to analyze the TERT rs2242652 polymorphism in breast cancer women and to test the correlation of such data with the prognosis and various clinical variables. Methods: The study was conducted as an observational clinical study of women with breast cancer. A blood sample was collected from the patient and PCR was performed to extract the DNA and to analyze the telomerase polymorphisms in this population. To ensure a more descriptive analysis, the data was used in the construction of tables and graphs, that were then studied in a qualitative manner. The associations were analyzed through direct correlation tests and were followed by comparisons of categorization groups. Results and discussion: Fifty-four women presented polymorphism of the telomerase hTERT gene rs2242652. They were divided into two groups according to the A or G allele that confer the GA/AA and GG gene variants. It was found that the GA/AA group had a trend towards more aggressive tumors, presenting 33% triple negative and 22% of tumors with HER2 overexpression, different from the GG group: 19% triple negative and 10% HER2 overexpression. More aggressive T4 tumors, were more expressive in the GA/AA gene variant group representing 20% of the patients, whereas in the GG group they represented only 8%. Conclusion: The data found in this study on the telomerase TERT gene polymorphism rs2242652 with breast cancer refers to a tendency found in tumors that have a more severe prognosis, to associate with the gene variant linked to the A allele of this gene, however a larger sample number is required for statistical confirmation. Citation Format: Miriam Alvares, Elisa Mascarenhas, Joao Matos. rs2242652 POLYMORPHISM OF THE hTERT GENE IN 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 PO5-25-09.
Abstract PO5-24-09: Optimizing the Therapeutic Treatment of Breast Cancer Through a Dual Data-driven Theoretical Model
Authors: A. Najafi
Journal: Cancer Research (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 PO5-27-08: Cytotoxicity and motility inhibitory effect of FA-Hep-CuS nanoparticles on breast cancer cells
Authors: David Arreola
Journal: Cancer Research (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.
Abstract PO5-27-09: Pharmacological eIF4E inhibition suppresses anti-tumor activity in ER+ breast cancer
Authors: Matthew Friedersdorf, Devon Blake, Sarah Thompson, Krista Marran, Jessica Sorrentino
Journal: Cancer Research (2024)

Abstract Elevated levels of eukaryotic initiation factor 4E (eIF4E) are found in a broad range of cancers, including breast, and have been associated with aggressive, drug resistant tumors. Furthermore, elevated eIF4E activity is sufficient to cause transformation in various cancers, while inhibition suppresses tumor growth. eIF4E, the main regulator and rate limiting factor of protein synthesis, is the downstream integrator of several important oncogenic signaling pathways (PI3K/AKT/mTOR, Ras/Raf/MEK, and Myc). Activation of eIF4E results in increased protein levels of key proliferation and metabolism proteins such as Cyclin D1 (CCND1) and Ornithine Decarboxylase 1 (ODC1), as well as an overall increase in cellular synthesis machinery, causing cellular growth and proliferation. Here, we describe the development and characterization of novel, potent, and selective eIF4E inhibitors. Compounds from this chemical series have nanomolar activity in multiple biochemical and biophysical m7G cap-competition assays as well as potent inhibition of translation in cellular and biochemical assays. In cells, these compounds rapidly and reversibly decrease protein levels of several oncogenes, including CCND1, leading to a G1 cell cycle arrest. We demonstrate that eIF4E inhibitors cause growth inhibition in a variety of breast cancer cell lines, including ER+ breast cancer. These inhibitors also inhibit growth of breast cancer lines with acquired resistance to Palbociclib with the same potency as the parental cell lines. Additionally, eIF4E inhibition shows an increased sensitivity in resistant cell lines when combined with standard of care (SOC), including Palbociclib. Select analogs from the series demonstrate favorable ADMET/PK properties with good oral bioavailability and low safety risk. Lastly, these compounds have demonstrated near complete tumor growth inhibition in non-breast cancer in vivo models. Ongoing experiments will address in vivo efficacy in ER+ breast cancer in both monotherapy and in combination with SOC. Citation Format: Matthew Friedersdorf, Devon Blake, Sarah Thompson, Krista Marran, Jessica Sorrentino. Pharmacological eIF4E inhibition suppresses anti-tumor activity in ER+ 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 PO5-27-09.
Abstract PO5-23-02: Targeted Axillary Dissection with Paramagnetic Marker Localization
Authors: Roland Reitsamer, Andreas Sir, Ernst Forsthuber, Florentia Peintinger
Journal: Cancer Research (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 PO5-27-07: A novel ROR1 inhibitor CPD86 suppresses Triple-Negative Breast Cancer cells via regulation of AKT/GSK3β pathway
Authors: Tram Ta, Victoria Reed, Nikhil Chandra, Nick Dwyer, Norman Fultang, Shradheya Gupta, Indrakant Singh, Bela Peethambaran
Journal: Cancer Research (2024)

Abstract Breast cancer is the second most commonly diagnosed cancer in women in the United States. The most aggressive subtype is triple negative breast cancer (TNBC), which accounts for 15-20% of new cases on average each year. Histologically, it is characterized by the absence of estrogen receptors (ER), progesterone receptors (PR) and human epidermal growth factor receptor 2 (HER2), which are typically targeted by hormone therapies such as tamoxifen, fulvestrant, or letrozole. Standard of care for TNBC includes traditional chemotherapy and radiation, which are detrimental to both cancerous and normal cells. Therefore, the lack of all hormone receptors in TNBC calls for the investigation of novel anti-cancer compounds that specifically target TNBC with minimal damage to non-cancerous tissues. Receptor orphan tyrosine kinase-like receptor 1 (ROR1) is an oncoprotein that is overexpressed in several human malignancies such as lung, breast, prostate and pancreatic cancers, but not in normal tissues. Inhibition of ROR1 signaling has shown to repress proliferation and induce apoptosis of cancer cells. Through in-silico docking and isothermal titration calorimetry, we identified a novel compound CPD86 that interacts with and inhibits ROR1. We hypothesize that CPD86 selectively targets TNBC cells by reducing the phosphorylation of AKT/GSK3β via the inhibition of ROR1. Our in vitro results suggest that CPD86 inhibits cell viability and induces intrinsic apoptosis of TNBC cells at a half-maximal inhibitory concentration of 2-5 µM, but not in normal breast epithelial cells with minimal ROR1 expression. CPD86 also represses TNBC cell migration and invasion while leaving non-malignant cells unharmed. This study highlights that ROR1 inhibitors could be developed as a potential therapeutic for TNBC and the data would serve as proof-of-concept justification for evaluation in other ROR1-upregulated cancers. Citation Format: Tram Ta, Victoria Reed, Nikhil Chandra, Nick Dwyer, Norman Fultang, Shradheya Gupta, Indrakant Singh, Bela Peethambaran. A novel ROR1 inhibitor CPD86 suppresses Triple-Negative Breast Cancer cells via regulation of AKT/GSK3β pathway [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 PO5-27-07.
Abstract PO5-27-11: A COMPARATIVE STUDY OF DIAGNOSTICS MADE BY FINE NEEDLE ASPIRATION (FNA) BIOPSY VERSUS TRU-CUT FOR BREAST PATHOLOGY IN A ONE STOP CLINIC PROGRAM IN MEDELLIN, COLOMBIA
Authors: Sara Gil, Carlos Agudelo, Jorge Castaño, Melissa Naranjo, Clara Piedrahita, Daniel Wilches, Kelly Corredor
Journal: Cancer Research (2024)

Abstract Breast cancer is the leading cause of morbidity and mortality among women in Colombia due to non-communicable chronic diseases. This has prompted health insurance companies to develop innovative initiatives to mitigate these negative outcomes. Since September 2018, Ayudas Diagnósticas SURA, in alliance with the Gustave Roussy Hospital and General Electric Healthcare has promoted a “One-stop clinic” program called: “TIEMPO PARA TI”. One of the primary challenges was to demonstrate that breast cytology, based on the Yokohama guidelines approved by The International Academy of Cytology has a high sensitivity, specificity, and diagnostic accuracy. The Yokohama system for classifying breast cytology is comprised of five categories: C1 not satisfactory, C2 benign, C3 atypical, C4 malignancy suspected, and C5 malignant. From September 2018 to December 2022, consecutive patients referred for breast biopsy and suspected of having breast cancer underwent triple assessment of breast tumor and were included in this retrospective study. Descriptive analysis was made using STATA v17 software to compare fine needle aspiration (FNA) biopsy versus Tru-cut. A total of 14,501 patients were included, 14.398 FNA and 14.401 trucut biopsies were performed. The comparative analysis showed a 99% concordance between categories 2, which correspond to benign lesions and 96.7% between categories 5, which correspond to malignant lesions. Our findings demonstrate that a well-executed FNA biopsy is not inferior to a trucut biopsy, as revealed by the Yokohama system, and offers significant advantages, such as cost-effectiveness and prompt diagnosis. Both techniques should be used with caution, considering their advantages and disadvantages. Citation Format: Sara Gil, Carlos Agudelo, Jorge Castaño, Melissa Naranjo, Clara Piedrahita, Daniel Wilches, Kelly Corredor. A COMPARATIVE STUDY OF DIAGNOSTICS MADE BY FINE NEEDLE ASPIRATION (FNA) BIOPSY VERSUS TRU-CUT FOR BREAST PATHOLOGY IN A ONE STOP CLINIC PROGRAM IN MEDELLIN, COLOMBIA [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 PO5-27-11.
Abstract PO2-23-10: Obesity May Modulate the Relationship Between High Mammographic Breast Density and Neoadjuvant Chemoresistance in Early Breast Cancer
Authors: Andrew Redfern, Veenoo Agarwal, Ellie Darcey, Lisa Spalding, Hilary Martin, Jennifer Stone
Journal: Cancer Research (2024)

Abstract Background - An inverse association has been described in a number of studies between mammographic breast density (MBD) and pathologic complete response (pCR) following neoadjuvant chemotherapy (NAC) for early breast cancer (BC), implicating high MBD in chemotherapy resistance. However, this effect has not been seen in all there is a paucity of data exploring whether this relationship extends the relationship beyond pCR to overall survival. This study aims to validate the relationship between MBD and pCR in patients undergoing NAC for early BC as well as to assess the relation of MBD with clinical complete response (cCR), relapse-free (RFS) and BC-specific survival (BCSS). Further, this study examines these associations stratified by body mass index (BMI). Methods - MBD was measured in contralateral mammograms in 127 women before NAC, using Cumulus software. As the study spanned the transition period from film to digital mammography, film mammograms were digitised using a high-powered scanner and processed full-field digital mammograms were extracted from the imaging storage facility. Basic patient, tumour and treatment demographics were collated including BMI. Percent dense area (PDA) was correlated with patient and tumour characteristics, short-term (pCR/cCR incidences), and long-term chemotherapy outcomes (RFS and BCSS). Results - Overall rates of cCR and pCR of 49% and 21% were observed across the whole cohort. Mean PDA was higher in those not undergoing cCR (p=0.041) and relapsing patients (p=0.041) but did not significantly vary by pCR or BC-deaths. As a dichotomous variable, high PDA relative to low PDA corresponded to lower cCR (40 v 58%, p=0.027), but no significant difference was seen for pCR (17.5 v 25.0%, p=0.15), BC relapse (38 v 30%, p=0.15) or BC-death (32 v 25%, p=0.20). High PDA (relative to low PDA) in patients with obesity (BMI &amp;gt;30kg/m2) was associated with lower pCR (0% v 28.1%, p=0.036) and numerically higher relapse rates (56% v 28%, p=0.063) and breast cancer deaths (56 v 28%, p=0.071. No such relationship was observed in patients with a BMI&amp;lt; 30kg/m2. Conclusion - Higher MBD associated with lower cCR and higher relapse but not with pCR or BC death. The inferior outcomes with high MBD were confined to patients with obesity in our study. Further analysis of the relationship between MBD and outcomes, including by BMI, is warranted. Citation Format: Andrew Redfern, Veenoo Agarwal, Ellie Darcey, Lisa Spalding, Hilary Martin, Jennifer Stone. Obesity May Modulate the Relationship Between High Mammographic Breast Density and Neoadjuvant Chemoresistance in Early 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 PO2-23-10.
Abstract PO2-24-07: Investigation into potential Estrogen Receptor (ER)-mediated regulation of Phosphoserine Aminotransferase (PSAT1)
Authors: Mary Sumlut, James Wittliff, Brian Clem
Journal: Cancer Research (2024)

Abstract Breast cancer is one of the leading causes of death among women. Expression of different proteins, such as hormone receptors (HR), are used to classify different types of breast cancer (i.e., HR+BC or triple negative breast cancer (TNBC)). While activation of the estrogen receptor (ER) in HR+BC is known to regulate a vast number of downstream targets in promoting breast cancer, there may be additional ER-regulated processes that are still unknown. The serine synthetic pathway has been demonstrated to be crucial in the proliferation and survival of select subtypes of breast cancer and phosphoserine aminotransferase 1 (PSAT1) is a key regulatory step. Previous studies have demonstrated higher PSAT1 levels in cells lacking ER and we now show a negative correlation between ERα protein levels and PSAT1 transcripts in human patient samples. This indicates that ER may potentially regulate PSAT1 expression. To initially investigate this potential relationship, either WT or constitutively active mutant ERα was expressed in TNBC cells (MDA-MB-231), which have high endogenous PSAT1 expression and no ER. Immunoblot was used to verify ERα levels and to assess effects on PSAT1. We observed a qualitative trend in decreasing PSAT1 levels with re-expression of ERα in the TNBC cells. While the variabilities in these results preclude any conclusion of a ERα:PSAT1 regulatory axis, the lack of a quantifiable effect on PSAT1 levels is postulated to be due to the transient nature of ERα expression/suppression in these systems. A more profound effect would be expected under durable changes in ERα levels and is a focus on-going studies. Citation Format: Mary Sumlut, James Wittliff, Brian Clem. Investigation into potential Estrogen Receptor (ER)-mediated regulation of Phosphoserine Aminotransferase (PSAT1) [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 PO2-24-07.