tbuckley/cabot-search huggingface dataset:
Application of the 2015 American Cancer Society screening mammography guidelines: Risk assessment for women ages 40-44.
Authors: Jennifer Kay Plichta, Alan Semine, Claire T Cronin, Taryn Rourke, Caroline Cole Block, Kevin S. Hughes
Journal: Journal of Clinical Oncology (2016)

1557 Background: The new ACS screening mammography guidelines suggest that only women with an above average risk require mammography screening between ages 40-44 (≥15% lifetime risk of breast cancer and/or ≥5% risk of BRCA mutation). In addition, the ACS recommends yearly MRI if the lifetime risk is ≥20%. We previously found that 50% of women ages 40-44 who were evaluated at an academic breast surgery practice would be eligible for mammograms, MRI, and/or genetic testing. Here, we sought to determine these numbers at a community breast imaging center, which we assumed would be a cohort more representative of the general population. Methods: Under IRB approval, we reviewed a database from 10/1/2015 - 12/28/2015 of patient-reported risk factors and family history at a community breast imaging center. We excluded all men, and women with a history of breast cancer. Using Tyrer Cuzick, Claus, or BRCAPRO, those with a ≥15% lifetime risk of breast cancer or ≥5% risk of BRCA mutation (eligible for genetic testing) were considered above average risk. Those with a ≥20% lifetime risk were also eligible for screening MRI. We assessed these results in Jewish and non-Jewish women. Results: 7357 women age ≥40 years without breast cancer were evaluated. Of these, 909 (12.4%) were ages 40-44 and constitute our cohort. Risk assessment identified 485 women (53.4%) who were eligible for mammography. Conclusions: At this community breast imaging center, 53.4% of women ages 40-44 would have been eligible for screening mammography. These numbers were higher in Jewish women. Thus, it is critical that women ages 40-44 have formal risk assessment, in order to identify those who would qualify for screening mammography, screening MRI, and genetic testing. Non-Jewish N=806 (89%) Jewish N=103 (11%) Total N=909 (100%) All mammography 410 (50.9%) 75 (72.8%) 485 (53.4%) Mammography, no MRI or genetic testing 169 (21%) 29 (28.2%) 198 (21.8%) Mammography + MRI, no genetic testing 176 (21.8%) 12 (11.7%) 188 (20.7%) Mammography + MRI + genetic testing 38 (4.7%) 24 (23.3%) 62 (6.8%) Mammography + genetic testing, no MRI 27 (3.3%) 10 (9.7%) 37 (4.1%)
Distant recurrences in triple negative breast cancer (TNBC) according to androgen receptor (AR) status.
Authors: Nadine M. Tung, Judy Ellen Garber, Michele R Hacker, Vanda Torous, Tessa Nalven, Brian Michael Alexander, Larissa Janeen Lee, Laura C. Collins, Stuart J. Schnitt
Journal: Journal of Clinical Oncology (2016)

1085 Background: TNBC comprises 15% of breast cancers and a subset expresses AR. Reported outcomes for estrogen receptor-negative or TNBC according to AR expression have been inconsistent. We assessed distant recurrence according to AR expression in patients with TNBC treated with chemotherapy. Methods: We retrospectively studied women with a first diagnosis of Stage I-III TNBC treated from 1996-2004 who received (neo)adjuvant chemotherapy. Clinical data were abstracted from medical records including age, tumor size, axillary node status and surgical, radiation and chemotherapy treatment. Histologic type, grade, lymphovascular invasion, and tumor infiltrating lymphocytes (TILs) were evaluated on H and E sections. Tissue microarrays were constructed (three 0.6mm cores/tumor) and sections were immunostained for AR; we categorized as AR-positive tumors in which ≥ 1% of cancer cells showed nuclear staining for AR and as strongly AR-positive tumors with > 10% nuclear staining. Cox proportional hazards regression was used to calculate the hazard ratio (HR) and 95% confidence interval (CI). Results: Among 94 cases of TNBC, 20.2% were AR-positive; 13.8% were strongly AR-positive. Most women (90.4%) received anthracycline-based chemotherapy and 46.8% also received a taxane; none received platinum chemotherapy. There was no significant difference in tumor size, nodal status or any histologic or treatment parameters between women with AR-positive and AR-negative TNBC other than a higher incidence of radiation treatment for women with AR-negative TNBC (78.7% vs 52.6%; p = 0.02). With a median follow-up time of 96.8 months (interquartile range: 36.7-117.5 months), distant recurrence was significantly less frequent in women with AR-positive TNBC than with AR-negative TNBC (5.3% vs 34.7%; p = 0.01) with an age-adjusted freedom from distant metastasis HR of 0.12 (95% CI: 0.02-0.89). Adding tumor size, nodal involvement, grade and TILs individually to the model did not appreciably alter the HR. Conclusions: We found that distant recurrence is significantly less likely among women with TNBC treated with anthracycline-based chemotherapy if the tumor is AR-positive.
Argininosuccinate synthase 1 (ASS1): A marker of unclassified hepatocellular adenoma and high bleeding risk
Authors: Elodie Henriet, Aya Abou Hammoud, Jean‐William Dupuy, Benjamin Dartigues, Zakaria Ezzoukry, Nathalie Dugot‐Senant, Thierry Leste‐Lasserre, Nestor Pallares‐Lupon, Macha Nikolski, Brigitte Le Bail, Jean‐Frédéric Blanc, Charles Balabaud, Paulette Bioulac‐Sage, Anne‐Aurélie Raymond, Frédéric Saltel
Journal: Hepatology (2017)

Hepatocellular adenomas (HCAs) are rare benign tumors divided into three main subgroups defined by pathomolecular features, HNF1A (H-HCA), mutated β-catenin (b-HCA), and inflammatory (IHCA). In the case of unclassified HCAs (UHCAs), which are currently identified by default, a high risk of bleeding remains a clinical issue. The objective of this study was to explore UHCA proteome with the aim to identify specific biomarkers. Following dissection of the tumoral (T) and nontumoral (NT) tissue on formalin-fixed, paraffin-embedded HCA tissue sections using laser capture methodology, we performed mass spectrometry analysis to compare T and NT protein expression levels in H-HCA, IHCA, b-HCA, UHCA, and focal nodular hyperplasia. Using this methodology, we searched for proteins which are specifically deregulated in UHCA. We demonstrate that proteomic profiles allow for discriminating known HCA subtypes through identification of classical biomarkers in each HCA subgroup. We observed specific up-regulation of the arginine synthesis pathway associated with overexpression of argininosuccinate synthase (ASS1) and arginosuccinate lyase in UHCA. ASS1 immunohistochemistry identified all the UHCA, of which 64.7% presented clinical bleeding manifestations. Interestingly, we demonstrated that the significance of ASS1 was not restricted to UHCA, but also encompassed certain hemorrhagic cases in other HCA subtypes, particularly IHCA.ASS1 + HCA combined with a typical hematoxylin and eosin stain aspect defined a new HCA subgroup at a high risk of bleeding. (Hepatology 2017;66:2016-2028).
Change in prostate biopsy outcomes and costs of care for prostate cancer in underserved population after changes in USPSTF guidelines.
Authors: Amit Mohan Algotar, Parminder Singh, Jennica Billins, Glen Thomazin
Journal: Journal of Clinical Oncology (2016)

1548 Background: This study investigates the impact of United States Preventive Services Task Force (USPSTF) guideline changes regarding prostate specific antigen (PSA) based screening for prostate cancer (PCa) on prostate biopsy outcomes and costs of care in a population of underserved men. Methods: Data were abstracted from male subjects ≥ 50years old who had a prostate biopsy and were part of the Inland Empire Health Plan. After reviewing data from 935 subjects, complete data were obtained from 580 subjects (430 subjects who had a biopsy after the guideline change and 130 who had biopsy before the guideline change). Direct medical cost of cancer care were obtained through claims data (Pharmacy, Professional and Institutional Claims) and were calculated for each member based on the services they had received. Results: Although PSA at time of prostate biopsy was not statistically different between the post and pre guideline subjects (Mean(SD), ng/ml: 6.3(6.2) vs 6.7(7.7), p = 0.73), the risk of being diagnosed with PCa as well as the risk of being diagnosed with high grade disease (Gleason score ≥ 7) was higher in the post guideline group as compared to the pre-guideline group (37.0% vs 30.7% (p = 0.11) and 75.5% vs 56.5% (p = 0.01) respectively). Results from logistic regression (adjusted for age, PSA and race) indicate that the odds of being diagnosed with high grade PCa amongst the subjects that had prostate biopsy after the guideline change was 2.8 times higher as compared to those subjects who had prostate biopsy before the guideline change (Odds ratio and 95% Confidence intervals: 2.8(1.30, 6.07)). Direct medical cost of care for PCa has increased by 78% in the post guideline change era as compared to those prior to the guideline change ($13,292.03 per subject as compared to $7,484.87 per subject respectively). Conclusions: Changes in USPSTF guidelines are associated with higher grade of disease at biopsy as well as cost of care. This could potentially be due to delay in the diagnosis due to lack of PSA screening leading to disease progression. Not only are these results concerning because of its magnitude but also because it has occurred in a short span of 3 years.
Regulation of body weight and energy homeostasis by neuronal cell adhesion molecule 1
Authors: Thomas Rathjen, Xin Yan, Natalia L Kononenko, Min-Chi Ku, Kun Song, Leiron Ferrarese, Valentina Tarallo, Dmytro Puchkov, Gaga Kochlamazashvili, Sebastian Brachs, Luis Varela, Klara Szigeti-Buck, Chun-Xia Yi, Sonja C Schriever, Sudhir Gopal Tattikota, Anne Sophie Carlo, Mirko Moroni, Jan Siemens, Arnd Heuser, Louise van der Weyden, Andreas L Birkenfeld, Thoralf Niendorf, James F A Poulet, Tamas L Horvath, Matthias H Tschöp, Matthias Heinig, Mirko Trajkovski, Volker Haucke, Matthew N Poy
Journal: Nature Neuroscience (2017)
Review of next generation sequencing outcomes in patients with metastatic breast cancer.
Authors: Irene Kang, Anishka D'souza, Darcy V. Spicer, Christy Ann Russell, Julie E. Lang, Maria Nelson, Howard Silberman, Janice M. Lu
Journal: Journal of Clinical Oncology (2017)

e12558 Background: Among patients with newly diagnosed breast cancer in the US, 6-10% will have metastatic disease. With many treatment options to choose from, Next Generation Sequencing (NGS) is a technology that can potentially guide treatment. However studies on the clinical use of NGS are currently limited. Methods: We identified patients with metastatic breast cancer treated at Norris Comprehensive Cancer Center and Los Angeles County Medical Center who underwent NGS with FoundationOne, a clinical-grade NGS tool. Medical records were reviewed for genetic findings, tumor type, treatment outcomes and impact of NGS testing. Results: NGS data derived from FoundationOne testing were analyzed in 27 patients tested between 2013 and 2017. The most commonly occurring mutations were TP53 and PIK3 occurring in 29% of tested patients; followed by MYC, CDH1 and CCND1 (26% each). Clinical data were available for 26 patients:18 patients were hormone receptor (HR) positive Her2 negative, 6 were triple negative, one had HR positive Her2 positive disease, and one had adenoid cystic pathology. A median of 4 mutations per patient (range 0-13) were detected by NGS testing. Twenty-one of 27 patients (78%) were found to have clinically actionable mutations with a median of 1 clinically actionable mutation (range 0-3) per patient. Of these patients, 10 (47%) received treatment directed at their mutation. Five patients were treated on clinical trial as a result of AKT, PTEN or ERBB2 mutations. An additional two patients had received targeted treatments empirically before the time of NGS and three cases are intended for future use. Patients had received on average 5 lines of therapy (range 0-13) at time of study. Conclusions: In patients with metastatic breast cancer, NGS provides data that may drive clinical care. Potential benefits include more precise selection of treatment regimens as well as identifying benefit from drugs that are not yet standard of care in breast cancer. Here we report that clinically actionable mutations are found in a majority of patients tested. Further study is necessary to determine the utility of NGS in this population.
CCND1 and CCND2 Mutations Are Frequent in Adults with Core-Binding Factor Acute Myeloid Leukemia (CBF-AML) with t(8;21)(q22;q22)
Authors: Ann-Kathrin Eisfeld, Jessica Kohlschmidt, Sebastian Schwind, Deedra Nicolet, James S. Blachly, Shelley Orwick, Chandni Shah, Maryam Bainazar, Karl Kroll, Christopher J Walker, Andrew J. Carroll, Bayard L Powell, Richard M. Stone, Jonathan E. Kolitz, Maria R. Baer, Albert de la Chapelle, Krzysztof Mrózek, John C. Byrd, Clara D. Bloomfield
Journal: Blood (2016)
Volumetric breast density, breast cancer subtypes and race.
Authors: Hitesh Shivalingappa, Mahvish Muzaffar, Kathryn Verbanac, Nasreen A. Vohra
Journal: Journal of Clinical Oncology (2016)

e12067 Background: Fully-automated volumetric methods for quantifying breast density have been shown to be reliable and take into account the 3-dimensional nature of breast tissue. BC is classified into several different subtypes which have varying associations with factors such as parity and race. The differences in volumetric breast density (VBD) among BC patients with different subtypes of BC have not been elucidated. We hypothesized that significant differences in VBD and the components that comprise VBD (i.e. fibroglandular volume (FGV) and total breast volume (BV)) occur in triple negative (TNBC) and hormone positive (HPBC) BC patients. Methods: We conducted a retrospective study of BC patients from Eastern North Carolina from 2006-2013. Age, race, body mass index (BMI), BC subtype and raw mammographic data for the contralateral cancer free breast were collected. Volpar (v1.5.12), an automated software, was used for estimating FGV, BV and VBD. Results: The average age, BMI, VBD, FGV and BV are summarized in the table below by BC subtype and race, A = African American, W = White. Conclusions: Overall AA cancer patients have a higher BMI, lower VBD and, higher FGV and BV compared to White patients regardless of BC subtype. TNBC patients were younger and had higher average FGV compared to HPBC patients. Association of volumetric density measures to BC subtypes may differ compared to visual measures. An ongoing case-control study will clarify these associations. Breast cancer subtypes (total n = 1,840). Variable mean±SD Hormone Positive n = 1348 (73%) Triple Negative n = 492 (27%) Race (n, %) A (398, 29.5%); W (929, 68.9%) A (249, 50.1%); W (237, 48.2%) Age (years) A (59±12); W (62±12) A (55±12); W (58±13) BMI (kg/m2) A (33.9±8.8); W (30.2±7.4) A (33.7±8.1); W (28.2±6.0) VBD % A (7.3±4.7); W (8.9±14.4) A (7.4±4.3); W (8.1±5.4) FGV cm3 A (66±38.6); W (57.5±35) A (72.03±35.9); W (58.1±30) BV cm3 A (1142.6±705.2); W (863.1± 474.5) A (1180.7±667.6); W (870.3± 447.1)
The impact of HIV infection on outcomes in patients with common non-AIDS defining malignancies: A systematic review and meta-analysis.
Authors: Sashidhar Manthravadi, Sheshadri Madhusudhana
Journal: Journal of Clinical Oncology (2016)

e13078 Background: HIV infection is associated with an increased risk for several non-AIDS defining cancers (NADC). An earlier meta-analysis (Shiels et al, 2009) had shown higher incidence of certain cancers in HIV patients. However, the influence that HIV status may have on long term outcomes in these patients is unclear. Methods: A systematic search of MEDLINE and Embase was performed, utilizing individual search strategies, to identify studies which described the impact of HIV infection in patients with Hodgkin’s lymphoma, leukemia and cancers of the liver, lung, anus, head and neck, stomach and kidney. Pooled hazard ratios (HR) with 95% confidence intervals (CI) were calculated using a random effects model. Results: After applying inclusion criteria, 22 studies were selected for inclusion in the meta-analysis. In these 22 studies, outcomes were reported on HIV status for Hodgkin’s lymphoma (3 studies), leukemia (1) and cancers of the liver (7), lung (9), anus (8), head and neck (4), stomach (1) and kidney (1). A total of 759,427 cancer patients were followed across these studies, of whom 4,663 were infected with HIV. Concurrent presence of HIV infection was associated with worse overall survival in cancers of the lung (HR 1.51; 95% CI 1.09- 2.10), liver (HR 1.41; 95% CI 1.15, 1.73), head and neck (HR 2.23; 95% CI 1.42- 3.51), anal canal (HR 1.86; 95% CI 1.28- 2.69), kidney (HR 2.36; 95% CI 1.86, 3.00), stomach (HR 2.5; 95% CI 0.9- 6.8), Hodgkin’s lymphoma (HR 4.09; 95% CI 3.59- 4.66) and leukemia (HR 6.5; 95% CI 1.7- 24.2). Substantial heterogeneity was found in most of these meta-analyses, reflecting the likely presence of treatment disparities and comorbidities in these patients that may have affected long term survival in cancer survivors with HIV. Conclusions: HIV infection is associated with adverse prognosis in cancer patients in population-based studies. Survival in HIV patients with cancer is highly variable and additional studies are required to ascertain the contribution of variation in tumor biology, treatment disparities and presence of comorbidity to this difference in survival.
Maintenance treatment with capecitabine and bevacizumab versus observation in metastatic colorectal cancer: updated results and molecular subgroup analyses of the phase 3 CAIRO3 study
Authors: K.K.H. Goey, S.G. Elias, H. van Tinteren, M.M. Laclé, S.M. Willems, G.J.A. Offerhaus, W.W.J. de Leng, E. Strengman, A.J. ten Tije, G.-J. M. Creemers, A. van der Velden, F.E. de Jongh, F.L.G. Erdkamp, B.C. Tanis, C.J.A. Punt, M. Koopman
Journal: Annals of Oncology (2017)
Expansion and Maintenance of Hematopoietic Stem and Progenitor Cells in Course of Long-Term Inhibition of CXCR4/CXCL12 Signaling
Authors: Darja Karpova, Julie Ritchey, Matthew Holt, Darlene Monlish, Laura G. Schuettpelz, Wei Yang, Jean-Pierre Levesque, Allison Robyn Pettit, Michael P. Rettig, Halvard Bonig, John F DiPersio
Journal: Blood (2016)
Benefit from chemotherapy in metastatic breast cancer: A retrospective analysis at the BC Cancer Agency—Vancouver Island Centre.
Authors: Natasha Qureshi, Adam McIntyre, Jason J. Hart, David William Fenton, John Paul McGhie, Nicol Macpherson
Journal: Journal of Clinical Oncology (2016)

e12505 Background: Chemotherapy (CTX) can palliate symptoms and modestly prolong survival in patients with metastatic breast cancer (MBC). From clinical trials we have an understanding of the toxicity, response rate, and progression free survival associated with earlier lines of CTX. The difficulty for both medical oncologists and patients is in estimating the likelihood of benefit from CTX in later lines of treatment, and how response in prior lines influences that estimation. Methods: We performed a retrospective review of 288 patients with Her2-negative or Her2-unknown MBC treated with at least two lines of CTX to identify predictors of benefit or lack of benefit to further lines of therapy at the BC Cancer Agency (Vancouver Island Centre) from 2000-2010. We assigned the score of “Benefit” to those who had improvement in disease symptoms and/or improvement on imaging, and then examined for predictors of that Benefit. Initial improvement but then progression prior to the completion of 6 cycles of CTX, or no change in symptoms or imaging through the 6 cycles, were scored as Minimal-Benefit. Treatment which was stopped prior to cycle 4 due to worsening of symptoms or progression on imaging, or if death occurred prior to cycle 4, was scored as No-Benefit. Results: 288 patients received two lines of CTX; 36% had Benefit to 1st line CTX, and 18% had Benefit to 2nd line CTX. 3rd line CTX was given to 163 patients and 14% had Benefit. The Benefit in lines 4, 5 and 6, were 12% or less. If Benefit or Minimal-Benefit was obtained in 1st or 2nd line, the chance of Benefit in line 3 was 18% compared to 8% in those patients who did not have Benefit or Minimal Benefit in the first two lines. The chance of Benefit decreased with subsequent lines of CTX for MBC. Obtaining Benefit to 1st line did not substantially increase the chance of Benefit in 2nd line compared to those who achieved No-Benefit in 1st line. Conclusions: In an unselected, non-clinical trials, population of patients with MBC treated with CTX the chance of Benefit was 14% or less in 3rd and subsequent lines of CTX. Response in earlier lines of treatment modestly modified the likelihood of such benefit.
Medical school entry requirements discriminate against poorer students
Authors: Anthea Tinker, Victoria Berdugo, Michael Buckland, Lois Crabtree, Anistta Maheswaran, Andrea Ong, Jasmine Patel, Emilia Pusey, Chandini Sureshkumar
Journal: BMJ (2017)

McCartney says that “student interview courses are unfair.”1 We have recently examined all the websites and …
Abstract P110: EBP50 Regulates Vascular Smooth Muscle Cell Growth by Skp2-Mediated Degradation of p21/cip1
Authors: Gyun Jee Song, Stacey Barrick, Kristen L Leslie, Nathalie M Fiaschi-Taesch, Alessandro Bisello
Journal: Circulation Research (2011)

The PDZ domain-containing scaffolding protein, Ezrin-Radixin-Moesin-binding phosphoprotein 50 (EBP50) regulates vascular stenosis following endoluminal vessel injury. Its expression in vascular smooth muscle cells (VSMC) increases after wire injury, and neointima formation is significantly reduced in EBP50 knockout (KO) mice. The molecular mechanisms underlying EBP50 actions in VSMC are unknown. Genetic ablation of EBP50 reduced VSMC proliferation and was associated with increased (5-fold) expression of the cell cycle inhibitor p21cip1 both in vessels and in primary cells. No differences in mRNA levels of p21cip1 were observed in WT and KO cells. However, the half-life of p21cip1 in KO VSMC was significantly longer than in WT VSMC (80 min vs. 45 min) and p21cip1 levels were similar in WT and KO VSMC treated with the proteasome inhibitor MG132. These observations suggest that EBP50 regulates post-translational degradation of p21cip1. The S-phase kinase-associated protein 2 (skp2) is a component of the E3 ligase complex that degrades p21cip1. The C-terminal four amino acids of skp2 (ProSerCysLeu) are a canonical PDZ-binding sequence. Indeed, co-immunoprecipitation and in-gel overlay assays demonstrated the direct interaction between EBP50 and skp2. Mutation of the C-terminal Leu to Ala (L424A-skp2) abrogated the interaction with EBP50. Skp2 expression was significantly lower in KO than in WT cells and inhibition of EBP50 expression by an shRNA lentivirus decreased skp2 expression in WT cells. Moreover, expression of skp2, but not of the mutant L424A-skp2, in WT cells reduced p21cip1 levels. Therefore, EBP50 regulates both expression and activity of skp2 with attendant effects on p21cip1 and VSMC proliferation. Collectively, these experiments show that EBP50, by regulating skp2 and p21cip1 expression, controls VSMC proliferation and the progression of neointima formation. These studies identify a novel function for EBP50 in the direct regulation of the cell cycle and provide a mechanistic basis for the remarkable effect of this scaffolding protein on vascular remodeling.
Left ventricular‐only pacing in heart failure patients with normal atrioventricular conduction improves global function and left ventricular regional mechanics compared with biventricular pacing: an adaptive cardiac resynchronization therapy sub‐study
Authors: Kevin V. Burns, Ryan M. Gage, Antonia E. Curtin, John Gorcsan, Alan J. Bank
Journal: European Journal of Heart Failure (2017)
Tonic B-cell receptor signaling in diffuse large B-cell lymphoma
Authors: Ondrej Havranek, Jingda Xu, Stefan Köhrer, Zhiqiang Wang, Lisa Becker, Justin M. Comer, Jared Henderson, Wencai Ma, John Man Chun Ma, Jason R. Westin, Dipanjan Ghosh, Nicholas Shinners, Luhong Sun, Allen F. Yi, Anusha R. Karri, Jan A. Burger, Tomasz Zal, R. Eric Davis
Journal: Blood (2017)