tbuckley/cabot-search huggingface dataset:
Abstract ED11-01: Is inflammatory breast cancer a genomically different type of breast cancer?
Authors: F. Howard
Journal: Cancer Research (2024)

Abstract Inflammatory Breast Cancer (IBC) is a unique and aggressive disease, constituting 2 - 4% of breast cancer diagnoses yet responsible for up to 10% of breast cancer related deaths. IBC remains a clinical diagnosis, without highly specific molecular markers, and the genomic drivers of the disease are incompletely characterized. The overrepresentation of human epidermal growth factor 2 amplification and triple-negative disease within IBC have confounded comparisons between IBC and non-IBC. Nonetheless, some consistent genomic observations have emerged that may begin to explain the characteristic behavior of IBC, supported by both comparative clinical studies and preclinical models. This session will review mutational analysis, gene expression profiling, and epigenetic findings that highlight similarities as well as subtle differences between IBC and non-IBC. Citation Format: F. Howard. Is inflammatory breast cancer a genomically different type of 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 ED11-01.
Abstract PO3-16-05: Mitochondrial DNA mutation detection in tumors and circulating extracellular vesicles of triple negative breast cancer patients for biomarker development
Authors: Kunwar Vikramdeo, Shashi Anand, Sarabjeet Sudan, Paramahansa Pramanik, Seema Singh, Andrew Godwin, Ajay Singh, Santanu Dasgupta
Journal: Cancer Research (2024)

Abstract Early detection of triple-negative breast cancer (TNBC) patients and their recurrence prediction are daunting tasks. We aim to develop mitochondrial DNA (mtDNA) based biomarkers to improve the management strategies of TNBC patients. We have undertaken mitochondrial genome (MG) enrichment and next-generation sequencing approaches to map the entire MG in 73 samples (64 tissues, 9 extracellular vesicle samples) from 32 highly-aggressive TNBC patients. Measurement of mtDNA and cardiolipin contents, in concert with NDUFB8 and SDHB proteins’ expression, was carried out in tumors and matched extracellular vesicles (EVs) of all the above TNBC patients. Overall, we identified 168 nonsynonymous mtDNA mutations, of which 73% (123/186) were coding and 27% (45/168) were non-coding. Twenty percent of mutations were nucleotide transversions. Respiratory complex I (RCI) appears to be the key target, which harbored 44% (74/168) of the overall mtDNA mutations. A panel of 11 hotspot mtDNA mutations was identified among 19-38% TNBCs, each of which was detectable in the matched EV samples with 82% specificity. Overall, 38% of the metastatic tumor-signature mtDNA mutations were detectable in matched EVs of the TNBC patients. An appreciable number of mtDNA mutations were homoplasmic (18%, 31/168), novel (14%, 23/168), and potentially pathogenic (9%, 15/168). The overall and RCI-specific mtDNA mutational load was recorded to be higher in African American (AA) compared to European American (EA) women with an exclusive abundance of respiratory complex (RC) protein NDUFB8 (RCI) and SDHB (RCII) therein. Increased mtDNA (p &amp;lt; 0.0001) content was measured in both tumors and matched EV samples along with an abundance of cardiolipin (p=0.0001) content in the EVs of the TNBC patients. Lethal tumor-signature mtDNA mutation detection and measurement of altered mtDNA and cardiolipin contents in the EVs at an early time point bear the potential to formulate noninvasive early detection and recurrence prediction strategies in TNBCs to improve the overall survival of the patients. Citation Format: Kunwar Vikramdeo, Shashi Anand, Sarabjeet Sudan, Paramahansa Pramanik, Seema Singh, Andrew Godwin, Ajay Singh, Santanu Dasgupta. Mitochondrial DNA mutation detection in tumors and circulating extracellular vesicles of triple negative breast cancer patients for biomarker development [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 PO3-16-05.
Abstract PO2-10-06: The Rising Burden of Contraception Requirements in Breast Cancer Clinical Trials: Time for Change?
Authors: Camila Chiodi, Munzir Hamid, Catherine Weadick, Maeve Hennessy, Ana Martin-Quesada, Louise Kenny, Matteo Lambertini, Ines Vaz Luis, Seamus O'Reilly
Journal: Cancer Research (2024)

Abstract Background: Breast cancer clinical trials often involve therapies with potentially deleterious effects on the fetus and the baby in the event of pregnancy or breastfeeding. Consequently, eligibility criteria include contraceptive requirements for both the patient and their partner. Patient feedback on the burden of requirements in clinical trials prompted an evaluation of changes in contraceptive requirements in breast cancer clinical trials over the past two decades. Methods: Breast cancer ClinicalTrials.gov trials protocols over three periods of enrollment were reviewed: 01/01/2001 - 01/01/2002, 01/01/2011 - 01/01/2012, and 01/01/2021 - 01/01/2022. Inclusion criteria: 1. Interventional studies including (neo)adjuvant or palliative systemic therapy, 2. Premenopausal female patients. Data, including the required number, types, and duration of contraceptive strategies, treatment regimen, and study design, were collated. A descriptive analysis by time period was performed. Results: 305 studies were included from the three periods: 63 (2001), 127 (2011), and 115 (2021). Of these, contraception requirements were specified in ClinicalTrial.gov protocol information in 4, 61, and 71 CT for 2001, 2011, and 2021, respectively, limiting our analyses in the two later periods. Complete data is available in Table 1. Conclusions: Our data demonstrates a time trend towards more stringent contraception requirements in breast cancer clinical trials inclusion criteria. The impact of contraception burden on enrollment, patient compliance, and investigator insight warrants further assessment. Citation Format: Camila Chiodi, Munzir Hamid, Catherine Weadick, Maeve Hennessy, Ana Martin-Quesada, Louise Kenny, Matteo Lambertini, Ines Vaz Luis, Seamus O'Reilly. The Rising Burden of Contraception Requirements in Breast Cancer Clinical Trials: Time for Change? [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 PO2-10-06.
Abstract Wrk2-02: Modelling the effects of cell-cell interactions in the tumor microenvironment from single cell variability
Authors: A. Laughney
Journal: Cancer Research (2024)

Abstract Multicellular programs underly emergent phenotypes in health and disease. Yet, deciphering the functional effects of interactions amongst cell types remains a major challenge. Cells typically send messages to their microenvironment by emitting ligands, which bind to complimentary receptors on the surfaced of target cells; then triggering a change in the behavior of the target cell. Complimentary ligand-receptor-pairs are well annotated and methods have been developed to infer cell-cell interactions from single cell expression data based on their mutual expression. However, these methods do not assess the effect of ligand-receptor-mediated interactions on the microenvironment. Thus, we developed ContactTracing – a fundamentally new, systems level approach that exploits inter- and intra-sample variability to infer ligand effects on gene expression in target (receptor-expressing) cells without prior knowledge of downstream signaling (Nature, 2023). Foundational work towards benchmarking and validation of this method was performed in isogenic breast cancer models distinguished by tumor cell-intrinsic rates of chromosome missegregation (a cellular process called chromosomal instability, or CIN). Through this, we identified tumor ligands emanating from an endoplasmic reticulum (ER)-stress response as potential mediators of immune suppression in chromosomally unstable tumors. Indeed, CIN-induced chronic STING activation led to rapid interferon-selective desensitization and a switch to ER-stress-dependent transcription. Moreover, inhibition of chronic STING - or key mediators of its unfolded protein response to ER-stress - suppressed metastasis in syngeneic models of melanoma, breast and colorectal cancer; validating this innovative methodology and identifying a targetable mediator of cancer metastasis. Citation Format: A. Laughney. Modelling the effects of cell-cell interactions in the tumor microenvironment from single cell variability [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 Wrk2-02.
Abstract PO3-12-02: SAFETY AND TOLERANCE OF THE USE OF SHOCK WAVE THERAPY IN LYMPHEDEMA SECONDARY TO THE TREATMENT OF BREAST CANCER
Authors: Patricia Lima Ventura, Cinira Haddad, Vanessa Sanvido, Afonso Nazário, Gil Facina, Amanda Estevao, Samantha Lopes de Almeida Rizzi
Journal: Cancer Research (2024)

Abstract Introduction: Lymphedema is a very common complication of breast cancer treatment. The first-line therapeutic method for lymphedema is Complex Physical Therapy. An option currently mentioned as an adjuvant and non-invasive treatment for lymphedema secondary to breast cancer is Shockwave Therapy. Objectives: To evaluate the safety and tolerance of shockwave therapy for the treatment of upper limb lymphedema secondary to breast cancer treatment. Methods: This is a quasi-experimental study carried out with 17 women who underwent breast surgery associated with axillary lymphadenectomy or Sentinel Lymph Node Biopsy and who had upper limb lymphedema secondary to the treatment of breast cancer. All were treated with complex physical therapy prior to the study. Four sessions of Shockwave Therapy were applied, 4000 shocks at 0.06 mJ/mm2, 1 time per week for 4 consecutive weeks. For that, the participants were evaluated through the application of questionnaires and physical examination and underwent shock wave therapy for the upper limb ipsilateral to the surgery. Results: After the intervention, none of the participants had skin lesions, blisters, desquamation or hyperthermia of the limbs, and 17.65% had skin redness. Most patients reported no change in their social life and that they felt safer in daily activities and very satisfied with the treatment. The patients showed improvement in upper limb functionality after the intervention versus baseline (p=0.02). No difference in limb volume and shoulder range of motion over time for all movements performed was found after the intervention and at the evaluated intervals. In addition, improvements were observed in some domains of the quality-of-life questionnaires. Conclusion: Shockwave Therapy proved to be safe and tolerable in patients with lymphedema, with improved functionality and no significant change in the volume of the affected limb. Keywords: Extracorporeal shock wave therapy; Lymphedema; Breast cancer. Citation Format: Patricia Lima Ventura, Cinira Haddad, Vanessa Sanvido, Afonso Nazário, Gil Facina, Amanda Estevao, Samantha Lopes de Almeida Rizzi. SAFETY AND TOLERANCE OF THE USE OF SHOCK WAVE THERAPY IN LYMPHEDEMA SECONDARY TO THE TREATMENT OF 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 PO3-12-02.
Abstract ED02-02: The Challenges of Lobular Carcinoma
Authors: T. King
Journal: Cancer Research (2024)

Abstract Infiltrating lobular carcinoma (ILC) and lobular carcinoma in situ (LCIS) were first described in the1940s by two Memorial Hospital pathologists, Foote and Stewart. They were most intrigued by the infiltrative appearance of these lobular cancers which they described as demonstrating large numbers of isolated, loose or dyscohesive cells of rather uniform size but of varying shape. We now recognize that this dyscohesive growth pattern is the result of loss of a functional e-cadherin protein; a distinguishing feature between ILC and invasive ductal carcinoma (IDC). Several studies comparing clinical features and outcomes between ILC and IDC have generated consistent findings. Lobular cancers are more likely to be ER+, larger, lower grade, less likely to be detected on MMG and more likely to have positive margins at breast conserving surgery (BCS), or to require mastectomy. Yet importantly, if BCS is successful, local recurrence and rates of contralateral breast cancer are equal for ILC and IDC. Although lobular cancers represents only 5-15% of all breast cancer, numerically, if ILC was an independent cancer in women, it would rank as the 6th most common cancer in women. Notably the incidence of ILC rose sharply in the late 80s throughout the 90s, and it has become clear that there is a strong relationship between ILC and hormone replacement therapy. Perhaps the “strongest” risk factor for ILC, is LCIS. Classic LCIS is an incidental finding – there are no pathnogmonic features on breast imaging or gross examination of tissue. On microscopic examination it is often multicentric and bilateral. Although originally considered a precursor to ILC and treated with mastectomy, over the years it was realized that rates of ipsilateral cancer in women who were not treated for LCIS were lower than expected and were quite similar to rates of contralateral breast cancer – and this combined with the fact that only 50% of the cancers were of the lobular phenotype led to a movement to consider LCIS as a high risk lesion. Contemporary data continue to support this management approach as rates of cancer development in women with a diagnosis of LCIS are consistently reported at 1-2% per year and the risk is conferred bilaterally, with a slightly higher representation of ILC in the ipsilateral breast. In this presentation we will review areas of clinical controversy, including the use of MRI, the safety of breast conservation, the role of neoadjuvant chemotherapy and the utility of genomic assays in patients with ILC. Citation Format: T. King. The Challenges of Lobular Carcinoma [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 ED02-02.
Abstract ED03-02: Mechanisms for the effects of incretin and dual-incretin to produce substantial weight loss
Authors: R. Seeley
Journal: Cancer Research (2024)

Abstract We are in the midst of a revolution when it comes to treating individuals with obesity. "Incretin" and "Dual-Incretin" drugs now can produce weight loss that was only possible via bariatric surgery just five years ago. Key questions remain concerning just how these drugs exert these powerful effects and how those effects compare to weight loss induced by bariatric surgery. Evidence points toward these drugs not just being "anorexic" agents that reduce food intake but rather lowering the "set-point" for body weight/body fat. The presentation will focus on how weight is regulated and how that system interacts with these newest classes of drugs. Citation Format: R. Seeley. Mechanisms for the effects of incretin and dual-incretin to produce substantial weight loss [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 ED03-02.
Abstract PO3-12-04: Pulmonary Complication related to Trastuzumab Deruxtecan. A pharmacovigilance study from 2022-2023 FAERS Database
Authors: Niraj Neupane, Himal Kharel, Sangharsha Thapa
Journal: Cancer Research (2024)

Abstract Background: The horizon of Trastuzumab Deruxtecan (T-DXd), an antibody-drug conjugate, has been expanding. After its promising results in HER2-positive/HER2-low Breast cancer, it has been on trial for other cancers, such as HER2-negative breast cancers, Gastrointestinal, lung, colorectal, urothelial, etc., and it has shown promising results in clinical trials. However, there have been reports of pulmonary adverse events associated with T-DXd, including interstitial lung disease (ILD) and pneumonitis. Understanding the occurrence and characteristics of these pulmonary complications is essential for optimizing patient care and ensuring the safe use of T-DXd. Using the FAERS (FDA Adverse Event Reporting System) database for 2022-2023 aims to see T-DXd-related pulmonary complications and guide healthcare professionals in monitoring and managing these adverse events effectively. Methods: We conducted a retrospective analysis of all reported cases of respiratory complications in patients using TDXD, utilizing data reported to the FDA Adverse Event Reporting System (FAERS) database for January 2022 to March 2023. We included patients of more than 18; these cases were identified and classified using the Medical Dictionary for Regulatory Activities (MedDRA) terminology. Results: In this study, a total of 296 cases of adverse events were reported in patients using TDXD. Among these cases, 74 (27%) were respiratory adverse events. The most frequently observed respiratory complications were interstitial lung disease (ILD) and pneumonitis, with 21 cases each, accounting for 56% of the total respiratory complications. Out of the 14 reported deaths in this cohort, pneumonitis was the most commonly seen respiratory complication, occurring in 8 patients, followed by pulmonary embolism and ILD, each reported in 4 patients. Conclusion: Respiratory complications were the most frequent among the reported adverse events, accounting for 27% of all cases. ILD and pneumonitis were the most common complications, with 14 deaths reported in this group. These findings underline the importance of closely monitoring and managing pulmonary adverse events in patients treated with T-DXd. Healthcare professionals can use this information to optimize patient care and ensure the safe use of T-DXd. However, it is important to note that this study was based on a database and has limitations such as underreporting bias and lack of a control group, which hinders establishing a causal relationship. Additional research is needed to identify risk factors and improve patient outcomes. Citation Format: Niraj Neupane, Himal Kharel, Sangharsha Thapa. Pulmonary Complication related to Trastuzumab Deruxtecan. A pharmacovigilance study from 2022-2023 FAERS Database [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 PO3-12-04.
Abstract PO1-08-05: Using the CTS5 Score to Predict Late Recurrence in Male and Female Estrogen Receptor-Positive Breast Cancer Patients: a SEER database analysis of 65,729 cases
Authors: Fenhua Wang, Fang Ren, Jian Qian, Yunxia Xu, Jiayi Wu, Yu Zong, Xidong Gu
Journal: Cancer Research (2024)

Abstract Purpose: The Clinical Treatment Score post-5 years (CTS5) score is a prognostic prediction tool to predict the risk of late distant recurrence in postmenopausal women with estrogen receptor-positive (ER+) breast cancer. Here we aimed to evaluate the prediction role of CTS5 in male breast cancer patients using the Surveillance, Epidemiology, and End Results (SEER) database. Methods: ER+ early male and female breast cancer patients from the SEER database 2010-2013 were included. Clinicopathological features and the CTS5 score between the gender groups were compared using chi-square test. Overall survival (OS) and breast cancer-specific survival (BCSS) were estimated by Kaplan-Meier plots and compared between the groups with Log-rank test and multivariate cox proportional hazard regression models was used to determine the relationship between the CTS5 score and breast cancer survival outcomes in different gender cohorts. Results: A total of 65,729 ER+ breast cancer patients were included in the study and 611 were men. Male breast cancer was more likely to be diagnosed later in life (&amp;gt;50 years old, 87.1% vs 73.6%, p &amp;lt; 0.001), with more aggressive biological features (grade Ⅱ 51.6% vs 47.2%, p &amp;lt; 0.001; grade Ⅲ 37.8% vs 28.3%, p &amp;lt; 0.001) , and higher tumor burden (stage Ⅱ 45.8% vs 32.9%, p &amp;lt; 0.001, stage Ⅲ 17.5% vs 10.5%, p &amp;lt; 0.001) when compared to female counterparts. More male patients were CTS5 intermediate- or high-risk than female patients (high 7.9% vs 6.3%, intermediate 41.1% vs 24.6%, low 51.1% vs 69.1%, p &amp;lt; 0.001). Patients were divided into 0-5 year and &amp;gt;5 year cohorts based on whether they had a BCSS event within 5 years. In the &amp;gt;5 year cohort, patients with CTS5 high- or intermediate- risk had worse survival outcomes compared with low-risk cases in male and postmenopausal female patients but not in premenopausal female patients. In the 0-5 year cohort, the CTS5 score was not predictive for disease recurrence in male or postmenopausal patients. Conclusion: Male breast cancer patients were more likely to have aggressive tumors and worse survival outcomes. The CTS5 score could be applied to predict breast cancer-specific mortality risk beyond 5 years in male ER+ breast cancer patients. Citation Format: Fenhua Wang, Fang Ren, Jian Qian, Yunxia Xu, Jiayi Wu, Yu Zong, Xidong Gu. Using the CTS5 Score to Predict Late Recurrence in Male and Female Estrogen Receptor-Positive Breast Cancer Patients: a SEER database analysis of 65,729 cases [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 PO1-08-05.