tbuckley/cabot-search huggingface dataset:
Abstract TS2-2: Biology, Vulnerabilities and Clinical Implications of CTC Clusters
Authors: N Aceto
Journal: Cancer Research (2020)

Abstract CTC clusters have recently emerged as key players in the metastatic process. With a combination of microfluidic technologies and single cell-resolution molecular analysis applied to breast cancer patients and mouse models, we gained fundamental insights into the biology, vulnerabilities, and clinical implications of CTC clusters. For instance, we found that their physical features enable molecular changes that promote stemness and metastasis, allowing us to define new treatments to suppress their metastatic potential. Further, we investigated CTC heterogeneity at the single cell level, revealing fundamental interactions that occur between CTCs and immune cells and that accelerate metastasis formation. Thus, our findings support a model whereby CTCs form multicellular aggregates with each other as well as with immune cells to expand their metastatic potential, providing a new rationale for targeting these interactions in breast cancer. Citation Format: N Aceto. Biology, Vulnerabilities and Clinical Implications of CTC Clusters [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr TS2-2.
Missing the Target
Authors: Christopher Iriarte, Henrikas Vaitkevicius, Francisco M. Marty, Amy L. Miller, Joseph Loscalzo
Journal: New England Journal of Medicine (2020)

A 58-year-old man presented to the emergency department with a 2-week history of pelvic pain on the left side, with subsequent development of severe pain in the abdomen, lower back, and groin. He also reported numbness originating near his umbilicus and spreading to his thighs. There was no antecedent trauma.
5-Azacitidine in patients with IDH1/2-mutant recurrent glioma
Authors: Laetitia Federici, Laurent Capelle, Maxime Annereau, Franck Bielle, Christophe Willekens, Caroline Dehais, Florence Laigle-Donadey, Khê Hoang-Xuan, Jean-Yves Delattre, Ahmed Idbaih, Francois Lemare, Stéphane de Botton, Marc Sanson, Mehdi Touat
Journal: Neuro-Oncology (2020)
Randomized study of a pedagogical tool on organ and tissue donation in high schools in Rio de Janeiro, Brazil
Authors: Victor Diniz, Jose Eulalio, Victoria Brant, Ingrid Vieira, Raphael Correa, Ingrid Ribeiro, Rodrigo Furtado, Assad Bon-Habib, Anna Carvalho, Daiane Soares, Victor Secomandi, Eduardo Fernandes, Felipe Mello, Ronaldo Andrade, Leandro Pimentel, Camila Girao, Camilla Cesar, Caio Wierzchon, Munique Siqueira, Jose Cardoso
Journal: International Journal of Surgery (2020)
Pediatric liver transplantation in Ankara University, Children’s Hospital. Comparision of two eras
Authors: Meltem Kologlu, Elvan Onur Kırımker, Zarife Kuloglu, Ceyda Tuna Kırşaçlıoğlu, Ufuk Ateş, Özlem Selvi Can, Tanıl Kendirli, Aydan Kansu, Kaan Karayalçın, Suat Fitöz, Deniz Balcı
Journal: International Journal of Surgery (2020)
Abstract P2-09-08: Breast cancer tumor sequencing coupled with germline genetic testing aids the identification of at-risk individuals for hereditary breast cancer disorders
Authors: Daniel E Pineda-Alvarez, Scott T Michalski, Meaghan Russell, Shan Yang, Ihn Young Song, Robert L Nussbaum, Edward D. Esplin
Journal: Cancer Research (2020)

Abstract Background: With the rise of precision medicine, hereditary cancer germline testing and tumor genetic testing have been increasingly used to inform the management of patients with cancer. Recent studies report that approximately 10% of patient’s tumors have clinically significant variants in genes known to predispose to a hereditary cancer syndrome. Here we report the concordance rate between tumor genetic testing and germline genetic testing in patients with breast cancer and review its impact on the patients’ management and implications for their relatives. Methods: In this study, we used de-identified data from 101 consecutive patients with breast cancer who underwent tumor genetic testing followed by germline testing with NGS-based hereditary cancer gene panels. Results: Tumor genetic testing results included likely pathogenic or pathogenic (LP/P) variants in BRCA2 (21%), BRCA1 (20%), TP53 (10%), CDH1 (7%), ATM (4.3%), PALB2,CHEK2, and PTEN (3.7% each), and PIK3CA (2.5%) among 22 other genes. In 33/101 cases (33%) the P/LP variant was also detected in the germline. Genes in which disease-causing variants were most frequently confirmed to be in the germline included: BRCA2 (36%), BRCA1(21%), PALB2 (12%), and CHEK2 (12%). Variants in ATM, FH, FANCA, and MSH6 were confirmed in the germline in &amp;lt;10% of patients with variants in these genes. Variants in the TP53, CDH1, and PIK3CA genes were detected in the tumor but not in the germline. In 1 case a pathogenic germline variant was detected in the BRIP1 gene but not reported in the tumor, because the gene was not included in the tumor testing panel. Conclusions: A significant proportion (33%) of patients with clinically significant variants in tumors were identified to carry the same variant in the germline, uncovering a previously unknown risk of hereditary breast cancer disorder. Notably, some genes had a high probability of variants occurring in the germline, while others were primarily seen in tumors. Performing simultaneous germline and tumor testing may inform susceptibility to a hereditary cancer disorder, identify targets for precision therapy, early detection of secondary malignancies, and guide genetic counseling for relatives. Citation Format: Daniel E Pineda-Alvarez, Scott T Michalski, Meaghan Russell, Shan Yang, Ihn Young Song, Robert L Nussbaum, Edward D. Esplin. Breast cancer tumor sequencing coupled with germline genetic testing aids the identification of at-risk individuals for hereditary breast cancer disorders [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-09-08.
Roles of Palmitoylation and the KIKK Membrane-Targeting Motif in Leukemogenesis By Oncogenic KRAS4A
Authors: Huanbin Zhao, Ping Liu, Ruihong Zhang, Min Wu, Donghe Li, Xuemei Zhao, Chun Zhang, Bo Jiao, Zhu Chen, Ruibao Ren
Journal: Blood (2015)
Abstract P4-14-12: Effects of hepatitis C virus infection on the safety of chemotherapy for breast cancer patients: A retrospective chart analysis
Authors: Saptaparni Ghosh, Minghua L Chen, Janice Weinberg, Naomi Y Ko
Journal: Cancer Research (2020)

Abstract Background: Hepatitis C virus (HCV) infection is a major health problem in the United States and breast cancer is the second most common cancer in US women. Despite these prevalent diseases, there is limited information available on the effects of a concurrent HCV infection among breast cancer patients receiving chemotherapy and the problems they face during their treatment. There are limited guidelines for chemotherapy treatment in HCV positive breast cancer patients. Methods: We performed a retrospective 2:1 matched case control analysis on breast cancer patients with a confirmed active HCV infection who received chemotherapy at Boston Medical Center between January 2000 and April 2015. Cases with HCV infection (n=6) were matched with controls (n=12) who were HCV negative. The controls were matched on age (decade) of diagnosis, stage of breast cancer, and intended chemotherapy regimen. We investigated dose delays, dose changes, hospitalization, hematologic reasons for dose delays, and variation in blood counts during the treatment period in these patients from their medical records. Statistical analysis was done using R version 3.4.0 to compare these outcomes of interest between the two groups. Fisher’s exact and Wilcoxon rank sum tests were used to compare the categorical and continuous variables respectively. Results: The HCV positive group was at a significantly higher risk of dose delays (100% vs. 33%, p = 0.01), dose changes (67% vs. 8%, p = 0.02), and hospitalization during chemotherapy (83% vs. 25%, p = 0.04) than their HCV matched controls. The risk of getting a dose delay due to hematotoxicity was significantly higher in the HCV positive group than the HCV negative group (83% vs. 8%, p = 0.003). The HCV positive patients took longer time to complete their treatment cycles than the HCV negative group. Conclusions: Chronic HCV infection in breast cancer patients receiving chemotherapy may be complicated by their active HCV infection. Treatment challenges due to dose changes, dose delays and hospitalizations were significantly more common when compared to controls. Chemotherapy delays and dose changes during breast cancer treatment has a negative consequence. In the era of curative treatment for HCV, future studies focused on the effect and treatment of concurrent HCV and breast cancer treatment is warranted. Citation Format: Saptaparni Ghosh, Minghua L Chen, Janice Weinberg, Naomi Y Ko. Effects of hepatitis C virus infection on the safety of chemotherapy for breast cancer patients: A retrospective chart analysis [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-14-12.
Abstract P5-04-21: Analysis of serum immune biomarkers for response to therapeutic personalized peptide vaccination in patients with metastatic breast cancer
Authors: Uhi Toh, Shuko Saku, Yuko Takao, Sayaka Sakurai, Miki Takenaka, Shigeki Shichijo, Kyogo Itoh, Yoshito Akagi
Journal: Cancer Research (2020)

Abstract Purpose: Our results from the previous clinical trials using personalized peptide vaccines (PPV) combined conventional chemo-hormonal therapies have confirmed the potential for clinical benefit in patients who had higher IgG antibody and/or CTL response to the immunized PPV (SABCS 2018 U Toh etc.). The aim of this study is to evaluate the association between the serum immunologic factors including cytokines, haptoglobin (HP), B-cell activating factor (BAFF) etc. and the clinical outcome of patients(pt) with metastatic breast cancer (mBC) who treated by personalized peptide vaccines (PPV). Methods: Peripheral blood samples from 57 pts and 52 pts obtained before and after the vaccination of PPV, respectively. Serum HP and IL-6 were analyzed by ELISA(R&amp;D Systems, Life Technologies)and bead-based multiplex assays(Luminex 200 system)were performed for GM-CSF,IFN-γ,TNF-α, BAFF, TGF-β, IFNγ-induced protein 10(IP-10), IL-1β, IL-2,-4,-5,-8, -10. The association between each factor and clinical outcome was statistically evaluated. Results: Pt’s group (n=28) with low BAFF and high HP level (&amp;gt;544 pg/ml), high IFN-γ and high HP level or low IL-8 and high HP level before PPV treatment showed a significantly shorter median survival time (MST; p=0.015;0.068;0.002, respectively). There was no difference in high BAFF, low IFN-γ or high IL-8 level group(n=29). In contrast, pt’s group with low serum level of IL-10, GM-CSF, IL-5, IL-4 and low HP level (&amp;lt;544 pg/ml MV) after PPV treatment associated with significantly shorter MST (p=0.002; 0.001; 0.001; &amp;lt;0.001, respectively). Conclusions: The combination of serum levels of HP and BAFF, IFN-γ or cytokines of IL-8, -10, - 5, -4 might be useful prognostic biomarkers for mBC pts receiving PPV therapy. Citation Format: Uhi Toh, Shuko Saku, Yuko Takao, Sayaka Sakurai, Miki Takenaka, Shigeki Shichijo, Kyogo Itoh, Yoshito Akagi. Analysis of serum immune biomarkers for response to therapeutic personalized peptide vaccination in patients with metastatic breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-04-21.
Comparison of Priority vs Standard US Food and Drug Administration Premarket Approval Review for High-Risk Medical Devices
Authors: Caroline Ong, Vy K. Ly, Rita F. Redberg
Journal: JAMA Internal Medicine (2020)

The mean cost of breast cancer screening was $353 per beneficiary screened (Table).The main contributor to this mean (SD) cost was initial screening mammography (mean [SD] per-person cost, $249 [$125]) followed by recall (mean [SD] perperson cost, $56 [$172]) and other diagnostic tests (mean [SD] per-person cost, $45 [$421]).The median cost of breast cancer screening was $250 (interquartile range, $174-367) per beneficiary screened (Table ).When extrapolating these costs to the population who have private insurance in the US, the total national cost of screening women in their 40s was $2.13 billion per year, most of which was accounted for by the initial screening mammography ($1.50 billion; Table ).There was substantial regional variation in breast cancer screening costs.The total annual mean (SD) costs of breast cancer screening varied from $151 ($258) to $751 ($1100) per beneficiary screened across HRRs (Figure).Discussion | We found that although fewer than half of the women aged 40 through 49 years who had private insurance and were eligible received annual breast cancer screening in 2017, the estimated annual national cost was $2.13 billion.These costs are borne despite the unclear tradeoff between clinical benefits and risks of screening women aged 40 through 49 years.Furthermore, the cost per beneficiary screened varied 5-fold across regions.Of note, the costs identified in this study were substantially higher than estimates used in previous cost analyses (eg, 2-dimensional mammography unit cost: $213 in this study, compared with $140-$155 in prior studies). 5,6ur data add clarity around the costs of breast cancer screening for women in their 40s, drivers of these costs, and magnitude of regional variation.
Sourcing Personal Protective Equipment During the COVID-19 Pandemic
Authors: Edward Livingston, Angel Desai, Michael Berkwits
Journal: JAMA (2020)

The editors of JAMA recognize the challenges, concerns, and frustration about the shortage of personal protective equipment (PPE) that is affecting the care of patients and safety of health care workers in the US and around the world.We seek creative immediate solutions for how to maximize the use of PPE, to conserve the supply of PPE, and to identify new sources of PPE.We are in-terested in suggestions, recommendations, and potential actions from individuals who have relevant experience, especially from physicians, other health care professionals, and administrators in hospitals and other clinical settings.JAMA is inviting immediate suggestions, which can be added as online comments to this article.
Peroral pancreatoscopy-assisted removal of internally migrated fractured pancreatic stent
Authors: Shujaath Asif, Rakesh Kalpala, D. Nageshwar Reddy
Journal: Endoscopy (2020)

Endoscopic removal of internally migrated pancreatic stents is sometimes challenging even in the hands of expert endoscopists, because of the high risk of pancreatitis, pancreatic ductal leak, and perforation. Often multiple sessions are required to achieve successful retrieval. Peroral pancreatoscopy (POPS) for direct visualization of the main pancreatic duct was initially described in 1976 by Kawai et al. [1]. Pancreatoscopy is used for visualization and histological diagnosis of intraductal papillary mucinous neoplasms [2] [3], and also to delineate pancreatic duct strictures and to differentiate between benign and malignant disease. It is also used for lithotripsy of pancreatic ductal stones [3] [4].
Protect our healthcare workers
Authors: Fiona Godlee
Journal: BMJ (2020)

For healthcare staff at the front line of the covid-19 pandemic, work has suddenly become a frightening place. Impossible decisions threaten long term psychological damage from moral injury, say Neil Greenberg and colleagues (doi:10.1136/bmj.m1211). And there is real and justified fear about personal safety, fuelled by a scandalous and widespread lack of personal protective equipment (PPE). Doctors have been reduced to sourcing improvised eye protection, making public appeals for respirator masks, and fundraising for supplies (doi:10.1136/bmj.m1286). Their families (my own included) are parcelling up masks and scrubs and sending them by post, reminiscent of the parcels fondly sent …
Abstract P5-08-23: Personalized, prevention decision aid developed for breast cancer risk-reducing discussions and interventions in the WISDOM study
Authors: Holly Keane, Yash Huilgol, W. Patrick Shibley, Yiwey Shieh, Deborah Goodman, Jeff Tice, Jeff Belkora, Karen Sepucha, Elissa Ozzane, Allison Fiscalini, Laura Esserman
Journal: Cancer Research (2020)

Abstract Problem statement: Breast cancer risk reduction has been validated by Level I evidence generated in large-scale clinical trials, however uptake of chemoprevention among women at high risk remains very low. Methods: A patient-facing shared decision-making aid was designed to inform women enrolled in the PCORI-funded WISDOM Study of their individualized breast cancer risk and ways to reduce their risk. It built upon a breast health decision tool used for the prior ten years. The tool displays the key factors that are used to calculate a participant’s risk (Breast Cancer Surveillance Consortium [BCSC] and Polygenic Risk Score). The aid also estimates the anticipated change in a participant’s risk due to particular risk-reduction interventions (medication, lifestyle). After Institutional Review Board approval, we used a mixed-methods analysis to evaluate the decision aid. Expert opinion was sought from decision scientists, low literacy experts, breast health specialists, epidemiologists, and breast cancer specialists, in order to generate a tool with suitable language and adequate communication of content. We piloted the decision-making aid with 15 elevated risk WISDOM Study participants without a common mutation associated with breast cancer. Results: To date, the pilot has enrolled 10 elevated-risk participants with an average age of 63. Six have completed the quantitative survey. 3 (50%) indicated that they would consider chemoprevention. 6 (100%) indicated that they would consider lifestyle changes, such as exercise or reducing their body mass index (BMI). 3 (50%) indicated the aid has been “extremely helpful” and 6 (100%) indicated that they had a better understanding of their breast cancer risk. Participants also indicated the benefit of visuals and greater engagement with high-risk counselors when using the aid. The full pilot data plus the ongoing experience will be presented. Conclusion: The WISDOM Study shared decision-making aid represents a novel, participant-centered approach to integrate breast cancer prevention and personal breast cancer risk. This decision aid will be used in the WISDOM Study to evaluate whether risk-based screening will improve uptake of chemoprevention in the WISDOM Study population. Citation Format: Holly Keane, Yash Huilgol, W. Patrick Shibley, Yiwey Shieh, Deborah Goodman, Jeff Tice, Jeff Belkora, Karen Sepucha, Elissa Ozzane, Allison Fiscalini, Laura Esserman. Personalized, prevention decision aid developed for breast cancer risk-reducing discussions and interventions in the WISDOM study [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-08-23.
Abstract ES4-1: Adaptive Resistance to Hormonal Therapy
Authors: S Fuqua
Journal: Cancer Research (2020)

Abstract While recurrences are delayed by the use of endocrine therapy (ET), resistance can evolve with the development of metastatic breast cancer (MBC) in about one-fourth of ER-positive patients. MBC is incurable with a median 5-year survival rate of less than 25%. We know that ET resistance can result from an adaptive process in which escape survival mechanisms are used to evade treatment. One of the best-characterized ET resistance mechanisms is transcriptional activation of growth factor receptor (GFR) signaling, and subsequent estrogen-independent activation of ER via “cross-talk” with downstream signaling from GFRs. We will discuss distinct mechanisms of ligand-independent activation of ER discovered using transcriptional profiling of metastatic, ET-resistant tumors. It is now estimated that ~20% of therapy-resistant MBCs contain ESR1 mutations. Recent data has also shown that mutations in the MAPK/RAS pathway and transcription factor regulatory programs (for example, MYC) only account for an additional 22% of recurrent breast tumors. Thus, acquired mutations alone do not account for the majority of ET resistance mechanisms in MBC. ER-positive breast cancer cell lines display profound transcriptional variability at the single cell level associated with the acquisition of therapy resistance. Recently, bulk and single cell RNA sequencing was used on sequential samples from patients with ER-positive, ET-resistant patients and identified RNA expression patterns that represented different cellular phenotypes, including an increased epithelial mesenchymal transition state that could provide a selective advantage for selective phenotypic subclones to dominate. We will focus our discussion of transcriptional reprograming as a major mechanism of ET resistance. Citation Format: S Fuqua. Adaptive Resistance to Hormonal Therapy [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr ES4-1.
Covid-19: trials of four potential treatments to generate “robust data” of what works
Authors: Anna Sayburn
Journal: BMJ (2020)

The World Health Organization (WHO) is to coordinate an international study of treatments for covid-19 that will focus on four potential treatment strategies.

Tedros Ghebreyesus, WHO director general, said on 18 March that the SOLIDARITY trial was a response to fears that “multiple small trials with different methodologies may not give us the clear, strong evidence we need about which treatments help to save lives.”1

The trial “is designed to generate the robust data we need, to show which treatments are the most effective,” he said. It will also be designed to put minimal burden on over-stretched hospitals.

The study will focus on four treatment options …