tbuckley/cabot-search huggingface dataset:
Abstract PO4-08-03: Prognostic Effect of Ductal Carcinoma in Situ in Breast Cancer with BRCA1/2 Mutations
Authors: Kyung-Hwak Yoon, Eun-Kyu Kim, Hee-Chul Shin
Journal: Cancer Research (2024)

Abstract Abstract Background: Although Breast Cancer Susceptibility Gene (BRCA)-associated invasive breast cancer has been extensively studied, there are few reports on ductal carcinoma in situ (DCIS) in patients with BRCA1/2 mutations. This study aims to evaluate the prognostic effect of DCIS in breast cancer patients with pathologic variants of BRCA1/2 genes. Methods: Retrospective analysis was performed on a prospective cohort of 157 patients who were found positive for BRCA1/2 mutations through genetic testing from August 2003 to January 2022 at Seoul National University Bundang Hospital. Survival outcomes were compared between patients who had both invasive ductal carcinoma (IDC) and DCIS components (IDC-DCIS group, n = 121) and patients who had IDC only (IDC group, n = 36). Cox regression analysis was performed for evaluation of predictive factors for recurrence. Results: Among the 157 patients, 65 (41.4%) patients showed BRCA1 mutations, 90 (57.3%) patients had pathological variants of BRCA2, and 2 (1.3%) patients tested positive for both BRCA1/2 mutations. There was no difference in baseline clinical characteristics between the IDC-DCIS and IDC groups. When pathological features were compared, the IDC-DCIS group was more likely to express positivity in both estrogen receptor (IDC 5 (13.9%) vs. IDC-DCIS 74 (61.2%), P &amp;lt; 0.001) and progesterone receptor status (IDC 5 (13.9%) vs. IDC-DCIS 67 (55.4%), P &amp;lt; 0.001). Tumors in the IDC group were associated with a higher histologic grade (P = 0.004). There was no statistically significant difference in 5-year disease-free survival between the two groups (IDC 83.6% vs. IDC-DCIS 89.3%, P = 0.989). In univariate Cox regression analysis, younger age at diagnosis was a significant predictor for recurrence (hazard ratio (HR) 2.236, P = 0.049); salpingo-oophorectomy showed a risk-reducing effect (HR 0.106, P &amp;lt; 0.001). Further multivariate analysis found only the effect of salpingo-oophorectomy to be prognostic (HR 0.112, P &amp;lt; 0.001). Presence of DCIS was not a risk factor for recurrence in patients with BRCA1/2 mutations (HR 1.006, P = 0.989). Conclusion: BRCA1/2-positive breast cancer with DCIS components is more likely to be hormone receptor-positive and of lower grade compared to patients with IDC only. A tailored approach might be necessary in establishing treatment options for breast cancer patients with BRCA1/2 mutations according to the presence of DCIS. Citation Format: Kyung-Hwak Yoon, Eun-Kyu Kim, Hee-Chul Shin. Prognostic Effect of Ductal Carcinoma in Situ in Breast Cancer with BRCA1/2 Mutations [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 PO4-08-03.
Abstract PO5-04-10: Clinical and prognostic value of MLN51 (Metastatic lymph node gene 51)/CASC3 (Cancer susceptibility candidate gene 3) in clinical breast cancer, connection with nodal and hormonal receptor status
Authors: Binbin Cong, Tracey Martin, Xiaoshan Cao, Robert E Mansel, Eleri Davies, Wen Jiang
Journal: Cancer Research (2024)

Abstract Introduction: Metastatic Lymph Node Gene 51 Protein (MLN51) also known as Cancer Susceptibility Candidate Gene 3 Protein (CASC3) or Barentsz (BTZ) is a molecule that was first identified in malignant breast tumours. The CASC3 gene encodes the protein that binds to mRNA and is a key component of the exon junction complex (EJC), playing an important role in the metabolism of mRNA and in cellular recovery after stress responses. It is not clear, however, if MLN51 has a clinical value in assessing the disease progression of breast cancer. Methods: We analysed the transcription expression levels of MLN51 in a cohort of human breast cancer tissues and correlated the expression pattern with clinical outcome, pathological type and hormonal receptor status. Results: High levels of MLN51 was found to be a favourable prognostic indicator for overall survival (p=0.008, Hazard Ratio [HR=0.262]), the prognostic value being independent of other clinical and pathological factors. Likewise, high levels of MLN51 were also a significant and independent predictive factor for disease free survival (DFS) (p=0.003, HR=0.262). It was found that the favourable prediction in both OS and DFS was associated with node positive tumours, with significance with OS (p=0.004), compared in node negative tumours (p=0.143) and to DFS (p=0.001 in node positive compared with p=0.079 in node negative tumours). Levels of MLN51 had a significant correlation with EGFR in both normal and tumour mammary tissues but correlated with Her-2 and Her-3 in tumour tissues only. The prognostic power of MLN51 for DFS was significant in both Her-2 positive and Her-2 negative (p=0.003 and p=0.012) tumours and in ER negative tumours (p=0.003). The prediction for OS by MLN51 was particularly strong for Her-2 positive and ER positive (p=0.007 for both) tumours. Conclusions: MLN51 (CASC3) is a favourable prognostic factor in patients with breast cancer. This is clearly linked to the nodal status and hormone receptor status, particularly ER and HER-2. Citation Format: Binbin Cong, Tracey Martin, Xiaoshan Cao, Robert E Mansel, Eleri Davies, Wen Jiang. Clinical and prognostic value of MLN51 (Metastatic lymph node gene 51)/CASC3 (Cancer susceptibility candidate gene 3) in clinical breast cancer, connection with nodal and hormonal receptor status [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 PO5-04-10.
Abstract PO4-20-02: A prospective, randomized, controlled clinical trial comparing different PEG-rhG-CSF administration times to treat chemotherapy-induced neutropenia and febrile neutropenia in early breast cancer
Authors: Xiaoming Zha, Jue Wang, Yinggang Xu, Jinzhi He, Ye Wang, Weiwei Zhang, Xinyu Wan, Wenjie Shi
Journal: Cancer Research (2024)

Abstract Background: Pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) injection time is still referred as recombinant human granulocyte CSF (rhG-CSF) as a treatment for preventing febrile neutropenia (FN) in patients with early breast cancer. The trial examined whether PEG-rhG-CSF injection on day 7 following chemotherapy was superior to injection on day 3. Patients and methods: Patients with early breast cancer were randomly assigned to receive a preventive injection on days 7 or 3 following chemotherapy. The experimental group (n = 80) received PEG-rhG-CSF treatment on day 7 after chemotherapy, whereas the control group (n=80) received it on day 3. The occurrence of grades 3–4 neutropenia and FN was the primary endpoint. The secondary endpoint was the frequency of PEG-rhG-CSF dose reduction. Results: Compared with the control group, the white blood count (WBC) or absolute neutrophil count (ANC) in the experimental group was higher on days 9 and 13 (P &amp;lt; 0.05) after chemotherapy, and the incidence of grade 3–4 neutropenia was lower (P = 0.038). The experimental group met the standard for lowering the PEG-rhG-CSF dose were more than that in the control group (69.74% vs. 35.06%, P &amp;lt; 0.001). Patients receiving a lower PEG-rhG-CSF dose had higher WBC count and ANC after chemotherapy, but were more likely to suffer from mild arthralgia. (P &amp;lt; 0.05). Conclusion: In comparison with PEG-rhG-CSF injection on day 3 after chemotherapy, the incidence of grade 3–4 myelosuppression is lower, and the safety is more manageable after the injection on day 7. Thus, more patients will receive dose reduction and lower patient medical costs. Citation Format: Xiaoming Zha, Jue Wang, Yinggang Xu, Jinzhi He, Ye Wang, Weiwei Zhang, Xinyu Wan, Wenjie Shi. A prospective, randomized, controlled clinical trial comparing different PEG-rhG-CSF administration times to treat chemotherapy-induced neutropenia and febrile neutropenia 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 PO4-20-02.
Abstract PO4-13-05: Spotlight on PSMA as a new theranostic biomarker for breast cancer
Authors: Sara Bravaccini, Stefania Cortecchia, Flavia Foca, Giovanni Martinelli, Sara Ravaioli, Maria Maddalena Tumedei, Federica Matteucci, Roberta Maltoni, Giovanni Paganelli, Francesca Poli, Maurizio Puccetti
Journal: Cancer Research (2024)

Abstract Breast cancer patients are risk-stratified on the basis of the subtype classification. However, this parameter is not completely accurate in discriminating between high- and low-risk disease, creating a need for a reliable marker to determine aggressiveness. Prostate-specific membrane antigen (PSMA) could fulfill this need given that it has been reported to be expressed by breast cancer tumor cells and the endothelial cells of tumor vessels. We analyzed 68 breast cancers (BC) of whom 14 luminal A, 28 Luminal B, 15 HER2 positive and 11 triple negative BC to assess whether PSMA expression by immunohistochemistry was different in the several tumor subtypes and was related to ki67 expression and stromal TILs. PSMA positivity was calculated as the number of positive vessels on 10 fields at 40X magnifications. Kruskal Wallis’s test was used to assess difference in PSMA positivity among BC subgroups and Dunn’s test was performed for post-hoc comparisons; Spearman’s rho coefficient was calculated to analyze the correlation among PSMA, KI67 and TILs. Our results show that median PSMA was higher both considering the number of positive vessels and the staining intensity in TNBC compared to Luminal A and B tumors (p&amp;lt; 0.001). Ki67 was higher in TNBC compared to Luminal A tumors (p&amp;lt; 0.001). We saw a correlation between PSMA and ki67, especially in HER2+ tumors (p=0.002), while a correlation between PSMA and TILs was observed in TNBC (p=0.014). The analysis of PSMA expression on the lymph nodes showed the same trend observed for the primary tumors given that it was higher in TNBC compared to HER2 positive and luminal cancers. Our results suggest that PSMA could be used as theranostic biomarker in BC considering that it is highly expressed in more aggressive tumors and the possibility to treat PSMA-expressing patients for anti-angiogenesis and/or radionuclide treatment. Citation Format: Sara Bravaccini, Stefania Cortecchia, Flavia Foca, Giovanni Martinelli, Sara Ravaioli, Maria Maddalena Tumedei, Federica Matteucci, Roberta Maltoni, Giovanni Paganelli, Francesca Poli, Maurizio Puccetti. Spotlight on PSMA as a new theranostic biomarker for 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 PO4-13-05.
Continuously improving outcome over time after second allogeneic stem cell transplantation in relapsed acute myeloid leukemia: an EBMT registry analysis of 1540 patients
Authors: Ann-Kristin Schmälter, Maud Ngoya, Jacques-Emmanuel Galimard, Ali Bazarbachi, Jürgen Finke, Nicolaus Kröger, Martin Bornhäuser, Matthias Stelljes, Friedrich Stölzel, Johanna Tischer, Thomas Schroeder, Peter Dreger, Igor-Wolfgang Blau, Bipin Savani, Sebastian Giebel, Jordi Esteve, Arnon Nagler, Christoph Schmid, Fabio Ciceri, Mohamad Mohty
Journal: Blood Cancer Journal (2024)
Abstract PO5-13-11: Quantitative Assessment of HER2 Expression in Intraductal Neoplasms of the Breast
Authors: Nay Nwe Nyein Chan, Haiying Zhan, Revekka Khaimova, Thazin Aung, Charles Robbins, Patricia Gaule, David Rimm
Journal: Cancer Research (2024)

Abstract HER2 (ERBB2) is an established prognostic and predictive marker for patients with invasive breast cancer and used in HER2-targeted therapy. The clinical and biological significance of expression of HER2 protein in patients with intraductal neoplasms of the breast is not well characterized. In this study, we used our HS-HER2 (High Sensitivity-HER2) which is a CAP/CLIA certified laboratory derived test (LDT) using quantitative immunofluorescence (QIF). We evaluated HER2 expression in DCIS (ductal carcinoma in situ), LCIS (lobular carcinoma in situ) and benign lesions to correlate with their clinicopathologic characteristics. Thirty- eight cases of DCIS, and fourteen cases of LCIS and thirty benign cases were selected from the Yale Pathology department archives and 252 ROIs (regions of interest) were annotated by a board-certified pathologist. DCIS is classified according to the three-tier nuclear grading system: low, intermediate, and high-nuclear grade. LCIS is classified as PLCIS (pleomorphic variant) and CLCIS (classic LCIS) according to the WHO classification of breast tumors. Serial sections of FFPE tumor specimens were used to accurately quantify the HER2 expression by the HS-HER2 assay and the acquisition by QuPath v.04 with Qymia extension. According to the LOD (limit of detection,3 amol/mm2), LOQ (limit of quantification, 9 amol/mm2) and LOL (limit of linearity, 23 amol/mm2) of the optimized HS-HER2 assay as performed in our CLIA lab shows a broad range of HER2 expression in both DCIS and LCIS lesions, ranging from 0.7 amol/mm2 to 111.4 amol/mm2 in DCIS and 3.6 amol/mm2 to 49.9 amol/mm2 in LCIS. High grade DCIS lesions express higher average HER2 levels (111.4 + 0.7 amol/mm2) than combined low and intermediate grade DCIS (77.9 +1.9 amol/mm2) with no significant difference between low/intermediate and high-grade DCIS. CLCIS lesions express higher average HER2 level (49.9 + 3.6 amol/mm2) than PLCIS (35.1 + 5.4amol/mm2) but again this is not statistically significant. HER protein expression is relatively low in benign lesions ranging from 0.8 to 8.4 amol/mm2. Using the HS-HER2 assay, our results show quantitative level HER2 levels in DCIS and LCIS breast lesions. These findings may be important as HER2 targeted therapies that work in gene-unamplified cancer (HER2 conjugated ADCs) gain broader usage in the clinic. Citation Format: Nay Nwe Nyein Chan, Haiying Zhan, Revekka Khaimova, Thazin Aung, Charles Robbins, Patricia Gaule, David Rimm. Quantitative Assessment of HER2 Expression in Intraductal Neoplasms of the Breast [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 PO5-13-11.
Abstract PS08-07: BL-B01D1, a first-in-class EGFRxHER3 bispecific antibody-drug conjugate, in patients with Locally Advanced or Metastatic Breast Cancer and other Solid Tumor: Results from a phase 1 study
Authors: Jiong Wu, Jian Zhang, Yiqun Du, Wen Zou, Muran Ding, Hui Yang, Sa Xiao, Hongwei Wang, Hai Zhu, Martin Olivo, Yi Zhu
Journal: Cancer Research (2024)

Abstract Background: BL-B01D1 is a first-in-class novel antibody drug conjugate (ADC) consisting of an EGFRxHER3 bispecific antibody bounded to a novel TOP-I inhibitor payload via a cleavable linker. We now present safety/efficacy data from a phase I study of BL-B01D1 in breast cancer. Methods: This study included patients (pts) with locally advanced or metastatic breast cancer (BC) and other solid tumors. BL-B01D1 was administered intravenously at doses of 2.5mg/kg Day 1 &amp; Day 8 every 3 weeks (D1D8Q3W) or 5.0mg/kg Day 1 every 3 weeks (D1Q3W) during dose escalation (D-ESC, i3+3) based on the information obtained during the first-in-human study in solid tumors. A subset of pts will be enrolled in the dose-expansion (D-EXP) phase. Results: As of June 26, 2023, 42 pts were enrolled and received at least one dose (D-ESC, n=8; D-EXP, n=34) of BL-B01D1. Only one DLT of febrile neutropenia was observed at 5.0mg/kg D1 Q3W, maximum tolerated dose (MTD) has not been reached. D-EXP was conducted at 2.5mg/kg D1D8 Q3W. Forty-one pts with BC and 1 pt with non-small cell lung cancer (NSCLC) were enrolled in this study. The most common TRAEs ( &amp;gt;10%, all grade/≥ G3) were leukopenia (67%/24%), neutropenia (55%/33%), anemia (55%/26%), thrombocytopenia (60%/24%), nausea (38%/0%), vomiting (38%/0%), stomatitis (31%/2%), asthenia (29%/0%), hypokalemia (21%/5%), aspartate aminotransferase increased (19%/0), alanine aminotransferase increased (19%/0%), decreased appetite (19%/0%), hypertriglyceridemia (19%/0%), hyperglycemia (19%/0%), hyperglycemia (17%/0%), weight decreased (14%/0%), diarrhea (12%/0%), epistaxis (12%/0%), hypercholesterolemia (12%/0%). No ILD was observed. Twenty-four pts. were evaluable for efficacy (at least 1 tumor assessment). Updated information will be provided during the meeting. Conclusions: BL-B01D1 demonstrated encouraging efficacy in metastatic/locally advanced breast cancer that have failed standard of care, especially in pts with TNBC. The safety profile showed adequate safety and tolerability. Clinical trial information: NCT05470348. Efficacy in Patients with Breast Cancer 1 Including pts whose PRs were not yet confirmed but still under treatment. Citation Format: Jiong Wu, Jian Zhang, Yiqun Du, Wen Zou, Muran Ding, Hui Yang, Sa Xiao, Hongwei Wang, Hai Zhu, Martin Olivo, Yi Zhu. BL-B01D1, a first-in-class EGFRxHER3 bispecific antibody-drug conjugate, in patients with Locally Advanced or Metastatic Breast Cancer and other Solid Tumor: Results from a phase 1 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 PS08-07.
Immunotherapy drives mesenchymal tumour cell state shift and TME immune response in glioblastoma patients
Authors: Josephine D Hendriksen, Alessio Locallo, Simone Maarup, Olivia Debnath, Naveed Ishaque, Benedikte Hasselbach, Jane Skjøth-Rasmussen, Christina Westmose Yde, Hans S Poulsen, Ulrik Lassen, Joachim Weischenfeldt
Journal: Neuro-Oncology (2024)

Glioblastoma is a highly aggressive type of brain tumor for which there is no curative treatment available. Immunotherapies have shown limited responses in unselected patients, and there is an urgent need to identify mechanisms of treatment resistance to design novel therapy strategies.
Meningioma: International Consortium on Meningiomas consensus review on scientific advances and treatment paradigms for clinicians, researchers, and patients
Authors: Justin Z Wang, Alexander P Landry, David R Raleigh, Felix Sahm, Kyle M Walsh, Roland Goldbrunner, Leeor S Yefet, Jörg C Tonn, Chloe Gui, Quinn T Ostrom, Jill Barnholtz-Sloan, Arie Perry, Yosef Ellenbogen, C Oliver Hanemann, Gerhard Jungwirth, Michael D Jenkinson, Ghazaleh Tabatabai, Tiit I Mathiesen, Michael W McDermott, Marcos Tatagiba, Christian la Fougère, Sybren L N Maas, Norbert Galldiks, Nathalie L Albert, Priscilla K Brastianos, Felix Ehret, Giuseppe Minniti, Katrin Lamszus, Franz L Ricklefs, Jens Schittenhelm, Katharine J Drummond, Ian F Dunn, Omar N Pathmanaban, Aaron A Cohen-Gadol, Erik P Sulman, Emeline Tabouret, Emelie Le Rhun, Christian Mawrin, Jennifer Moliterno, Michael Weller, Wenya (Linda) Bi, Andrew Gao, Stephen Yip, Maximilian Niyazi, Kenneth Aldape, Patrick Y Wen, Susan Short, Matthias Preusser, Farshad Nassiri, Gelareh Zadeh
Journal: Neuro-Oncology (2024)

Abstract Meningiomas are the most common primary intracranial tumors in adults and are increasing in incidence due to the aging population and increased access to neuroimaging. While most exhibit nonmalignant behavior, a subset of meningiomas are biologically aggressive and are associated with treatment resistance, resulting in significant neurologic morbidity and even mortality. In recent years, meaningful advances in our understanding of the biology of these tumors have led to the incorporation of molecular biomarkers into their grading and prognostication. However, unlike other central nervous system (CNS) tumors, a unified molecular taxonomy for meningiomas has not yet been established and remains an overarching goal of the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy-Not Official World Health Organization (cIMPACT-NOW) working group. Additionally, clinical equipoise still remains on how specific meningioma cases and patient populations should be optimally managed. To address these existing gaps, members of the International Consortium on Meningiomas including field-leading experts, have prepared this comprehensive consensus narrative review directed toward clinicians, researchers, and patients. Included in this manuscript are detailed overviews of proposed molecular classifications, novel biomarkers, contemporary treatment strategies, trials on systemic therapies, health-related quality-of-life studies, and management strategies for unique meningioma patient populations. In each section, we discuss the current state of knowledge as well as ongoing clinical and research challenges to road map future directions for further investigation.
Postprandial symptoms in disorders of gut-brain interaction and their potential as a treatment target
Authors: Alexander C Ford, Heidi M Staudacher, Nicholas J Talley
Journal: Gut (2024)

Postprandial, or meal-related, symptoms, such as abdominal pain, early satiation, fullness or bloating, are often reported by patients with disorders of gut-brain interaction, including functional dyspepsia (FD) or irritable bowel syndrome (IBS). We propose that postprandial symptoms arise via a distinct pathophysiological process. A physiological or psychological insult, for example, acute enteric infection, leads to loss of tolerance to a previously tolerated oral food antigen. This enables interaction of both the microbiota and the food antigen itself with the immune system, causing a localised immunological response, with activation of eosinophils and mast cells, and release of inflammatory mediators, including histamine and cytokines. These have more widespread systemic effects, including triggering nociceptive nerves and altering mood. Dietary interventions, including a diet low in fermentable oligosaccharides, disaccharides, monosaccharides and polyols, elimination of potential food antigens or gluten, IgG food sensitivity diets or salicylate restriction may benefit some patients with IBS or FD. This could be because the restriction of these foods or dietary components modulates this pathophysiological process. Similarly, drugs including proton pump inhibitors, histamine-receptor antagonists, mast cell stabilisers or even tricyclic or tetracyclic antidepressants, which have anti-histaminergic actions, all of which are potential treatments for FD and IBS, act on one or more of these mechanisms. It seems unlikely that food antigens driving intestinal immune activation are the entire explanation for postprandial symptoms in FD and IBS. In others, fermentation of intestinal carbohydrates, with gas release altering reflex responses, adverse reactions to food chemicals, central mechanisms or nocebo effects may dominate. However, if the concept that postprandial symptoms arise from food antigens driving an immune response in the gastrointestinal tract in a subset of patients is correct, it is paradigm-shifting, because if the choice of treatment were based on one or more of these therapeutic targets, patient outcomes may be improved.