bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multicenter Italian bone metastasis database: First prospective data on breast cancer patients.
Authors: Bongiovanni Alberto , Foca Flavia , Fantini Manuela , Forcignano Rosachiara , Artioli Fabrizio , Berardi Rossana , Campadelli Enrico , Procopio Giuseppe , Silvestris Francesco , Riva Nada , Gurrieri Lorena , Di Menna Giandomenico , Recine Federica , Fausti Valentina , Debonis Silvia Angela , Mercatali Laura , Spadazzi Chiara , Menis Jessica , Vespignani Roberto , Ibrahim Toni ,   Banca Dati Metastasi Ossee Study Team
Published: May 2020

e13072 Background: Bone Metastases (BM) are still the main cause of morbidity and morbility in cancer patients because of their complications defined as skeletal-related events (SREs).SREs reduce pts quality of life and are associated with an increasing in social and health costs. At present, data concerning BM are mainly obtained retrospectively from monocentric experiences. Methods: We performed a multicentre prospective observational study of patients with BM from breast cancer (BC) with at least 6 month (m)'s follow-up who were registered in a prospective BM database (BMDB). Detailed information on patients at first diagnosis of BM was recorded in a custom-built software system, updated every 6 m by participating centres and reviewed by the coordinator centre.All pts have signed an informed consent. Results: Since October 2014,618 pts with BM from solid tumors were enrolled of whom 220 have BC as primitive site with a 6 m follow-up. Median age was 62 y (range 26-86). Median Follow up was 34 m (6-149). At enrolment 109 (50%) had only BM and 109 (50%) pts had concomitant visceral and BM. Median time to first BM was 47 m (range 0-312) in Bone only disease and 78.6 m in pts with visceral bone metastases. Disease Free interval (DFI) was different according to BC molecular subtypes and stage. The univariate hazard ratio (HR) for visceral or bone metastasis was higher in luminal B tumors (1.56, 95% confidence interval [CI]:1.1-2.3) (p = 0.002), basal-like (2.50, 95% CI:1.1-6.0) (p = 0.043), and HER2-enriched tumors (1.37, 95% CI:0.78-2.4) (p = 0.273). DFI for pts with stage I disease at diagnosis of primary BC was longer than that for stage III pts (median 67.2 m, 95%CI:53.1-96.1, vs. 58.1 m, 95%CI:41.9-73.4), with a HR of 1.84 (95% CI:1.1-3.0) (p = 0.015) for the stage III group, and 0.98 (95% C.I.:0.6-1.5) (p = 0.930) for the stage II group. During BM disease, 98 pts had at least 1 SREs . Zoledronate was used in 69.1% and Denosumab in 28.3% of cases. First line treatment was hormone-based (n = 105, 50.7%) chemo-based therapy (n = 80, 38.7%) and chemo+ormono based (n = 20, 9.7%). During follow up progression disease occurred in 167 pts. Median progression-free (mPFS) and overall survival calculated from metastatic disease diagnosis (mOS) were 15.1 m (95%CI 12.6-18.4) and 66.8 m (95%CI 52.1-79.2),respectively. Conclusions: This study presents prospective data about a cohort of BC pts enrolled at the first BM occurrence and followed over the time, extrapolated by the multicentric observational BMDB in order to better understed the clinical history of breast cancer and bone metastases.
Del-1 and MFG-E8 expression to differentially modulate prognosis of patients with triple-negative breast cancer.
Authors: Lee Soo Jung , Park Ho Yong , Jung Jin Hyang , Lee Jeeyeon , Lee In Hee , Park Ji-young , Chae Yee Soo 
Published: May 2020

e13093 Background: Del-1 was previously found to be prognostic biomarker in early breast cancer patients. Del-1 shares both structural and functional homology with Milk fat globule-epidermal growth factor-factor VIII (MFG-E8). To date, the biological functions of Del-1 and MFG-E8 have not been sufficiently compared in side-by-side experiments. MFG-E8 is a secreted glycoprotein from macrophages that promotes clearance of apoptotic cells. In this study, we investigated the function of MFG-E8 and Del-1 and prognosis in a large cohort of EBC patients. Methods: The MFG-E8 levels were measured using a qRT-PCR in breast cancer cells (MDA-MB-231, Hs578T, MCF7, SK-BR3, and T-47D), and tissues from 20 patients with EBC. The effects of MFG-E8 and Del-1 on cell proliferation, migration, and invasion were determined using MTT, wound healing, and Matrigel Transwell assays. The expressions of MFG-E8 and Del-1 protein were detected by immunohistochemical staining in 436 tumor tissues. The relationship between MFG-E8, Del-1 expression levels and clinicopathological features were evaluated. Results: MFG-E8 and Del-1 levels were significantly elevated in MDA-MB-231 and Hs578T cell lines (p < 0.001). Given that MFG-E8 and Del-1 share similar protein structure, we wanted to explore the effect of dual knockdown of MFG-E8 and Del-1 in migration and invasion assay. As expected, knockdown of Del-1 alone decreased cell migration in TNBC cell lines, but dual knockdown of MFG-E8 and Del-1 showed reduction was restored. Dual knockdown of MFG-E8 and Del-1 showed consistent result in invasion assay. Down-regulation of Del-1 inhibited TNBC cells invasion and recovered by the MFG-E8 knockdown. Interestingly, for the 436 patients, Del-1 high- and MFG-E8 low- expression shows correlation with aggressive histologic grade, high Ki-67 (p < 0.001 and p = 0.042, respectively) and shorter survival outcome (distant disease free survival p = 0.028, breast cancer specific survival p = 0.001). Conclusions: Overall, these findings suggest that MFG-E8 and Del-1 protein expression could be a prognostic marker for patients in triple negative breast cancer (TNBC). Thus, MFG-E8 reduction may contributes to tumorigenesis by increasing Del-1. However, functions of Del-1 and MFG-E8 have not yet been thoroughly analyzed, further studies are required.
Physician treatment preferences for metastatic triple negative breast cancer (mTNBC) in an era of immunotherapy.
Authors: Gajra Ajeet , Wojtynek Jeffrey , Dokubo Igoni , Jeune-Smith Yolaine , Kish Jonathan , Feinberg Bruce A. 
Published: May 2020

e13095 Background: TNBC accounts for 10-20% of all breast cancer and has poor prognosis. Guidelines now list atezolizumab with nab-paclitaxel (ANP) as preferred for mTNBC w/ PD-L1 expression > 1%. We sought to assess current mTNBC prescribing and sequencing preferences for first-line (1L), second-line (2L), and third-line (3L) therapy among U.S. community oncologists (c-oncs). Methods: C-oncs were presented 4 hypothetical mTNBC clinical scenarios (CS 1-4) via web-based survey. CS differed by PD-L1 expression, menopausal status, prior adjuvant therapy and nature of metastases (bulky liver, lung, bone) but were otherwise uniform in terms of being asymptomatic, BRCA negative, with identical response extent and duration of each line of therapy. Respondents selected their preferred treatment for 1L, 2L, and 3L in each CS in the following categories: single agent (SA) chemotherapy, combination chemotherapy (CC), or ANP. The proportion of c-oncs selecting each treatment approach per CS for each line of therapy was calculated. We describe these preference patterns and how these may deviate from current guidelines. Results: 47 c-oncs participated from across the U.S. (northeast = 23%, midwest = 28%, south = 32%, west = 17%): mean years in practice was 22.7 and mean number of mTNBC patients under treatment was 18.8. The proportion of c-oncs preferring SA, CC or ANP per CS per line of therapy is listed in the table. Deviations from guidelines include preferences for: 1L ANP despite PD-L1 < 1% (26% in CS 1 and 4); 1L CC (45%) in asymptomatic bone only disease (CS1); 2L CC (19-34%) in asymptomatic visceral metastases (CS 2, 3 and 4). The SA 2L (74%)/3L (90%) preferences: capecitabine (36% 2L; 18% 3L) and eribulin (24% 2L; 35% 3L). Gemcitabine + carboplatin was the preferred CC regimen in 2L (50%) and 3L (28%). Conclusions: There is deviation from current guidelines in the treatment preferences for mTNBC patients among c-oncs, specifically the preference for ANP in PD-L1 negative patients and CC in 2L and 3L for asymptomatic patients. [Table: see text]
Economic evaluation of SP142 IHC assay versus 22C3 IHC assay in patients with unresectable locally advanced or metastatic triple-negative breast cancer in the Brazilian private healthcare system.
Authors: Shimabukuro Ho Rodrigo , Mioti Sebastião Mariana , Carvalho Joao , Neves Tomás , Nussbaum Micha 
Published: May 2020

e13097 Background: The IMpassion130 trial has demonstrated that atezolizumab plus nab-paclitaxel results in significant clinical benefits for patients with unresectable locally advanced or metastatic (aTNBC). The SP142 IHC assay is a clinically validated and FDA-approved PD-L1 test to identify patients with aTNBC for treatment with atezolizumab plus nab-paclitaxel. A post hoc analysis of IMpassion130 evaluated two other PD-L1 IHC assays, 22C3 and SP263, for analytical and clinical concordance with SP142 and the PD-L1 prevalence by each assay. The prevalence of PD-L1+ per SP142 (tumor-infiltrating immune cells 1%), 22C3 (combined positive score1) and SP263 (tumor-infiltrating immune cells 1%), were 46%, 81% and 75%, respectively. The study compared only SP142 assay with 22C3 assay because patients with SP142 negative and 22C3 positive did not demonstrate a significant clinical benefit for progression-free survival (PFS) and overall survival (OS). Therefore the study aimed to demonstrate the economic impact of these assays in the treatment with atezolizumab plus nab-paclitaxel. Methods: Data of PFS and OS from the post hoc analysis of Impassion130 were extracted to develop a Markov model to simulate the clinical and economic impact of the patient with atezolizumab plus nab-paclitaxel guided by SP142 and 22C3 assays. The analysis considered the cost of atezolizumab+nab-paclitaxel, the cost associated with the management of the adverse events and the cost of the assay. The costs were based on CBHPM (Classificação Brasileira Hierarquizada de Procedimentos Médicos), CMED PF18% (Câmara de Regulação do Mercado de Medicamentos) and local publications. An univariate sensitivity analysis was performed. Results: The study demonstrated that SP142 assay has the potential to save 175,917 BRL (45,595 USD) with atezolizumab plus nab-paclitaxel per patients with aTNBC in three years. Conclusions: The SP142 assay can optimize the use of atezolizumab plus nab-paclitaxel avoiding its use in patient who will not have a significant clinical improvement.
Comprehensive profiling of MDM2/TP53 genomic aberration in Chinese patients with diverse malignancies.
Authors: Zhou Dongkai , Wang Weilin , Yan Sheng , Ye Song , Wu Yingsheng , Ding Yuan , Sun Qiang , Qian Xiaohui , Gao Bingqiang , Kong Yang , Yang Qifan , Ji Weiping , Zheng Zhihai , Zhou Xiumin , Xu Weihua , She Mingjin , Yang Yong , Dong Qiantong , Yu Yaojun , Zhang Shiyue 
Published: May 2020

e13508 Background: Murine double minute-2 (MDM2) has increasing clinic relevance as preclinical and early clinical evidences have showed that the MDM2 inhibitors are promising alternative treatments for patients with MDM2-amplified (-amp) and TP53-wild-type (-WT) tumors by preventing TP53 protein degradation. However, exploration into genomic landscape of MDM2/TP53 across various solid tumors in Chinese patients is still limited. Methods: Formalin-fixed, paraffin-embedded (FFPE) tumor samples were collected from 10010 Chinese patients with solid tumors and subjected to a clinical-grade next-generation sequencing (NGS)-based 450 gene panel testing carried out by a College of American Pathologists (CAP) accredited and Clinical Laboratory Improvement Amendments (CLIA) certified laboratory. Genomic alterations (GAs) including single base substitutions, short and long insertion/deletions (Indels), copy number variations, gene fusions, and rearrangements were analyzed. Tumor mutational burden (TMB) was measured by a NGS algorithm. Results: Amplification of MDM2 occurred in 3.3% of Chinese patients. MDM2-amp was detected most frequently in soft tissue sarcoma (STS, 11.4 %), melanoma (10.3 %) and osteosarcoma (6.3 %). Notably, MDM2-amp was revealed to be mutually exclusive with TP53-mut in most tumor types other than esophageal carcinoma (93.9 %), head and neck carcinoma (68.4%) and ovarian carcinoma (50 %). Tumors with highest frequencies of MDM2-amp/ TP53-WT were melanoma (100%), osteosarcoma (100%) and urothelial carcinoma (100 %). The most common co-altered genes accompanied with MDM2-amp were FRS2 (84%), CDK4 (38%), EGFR (26%), TP53 (17%) and GLI1 (14%). 82.8% patients who had one or more co-alterations potentially targetable with either FDA-approved or investigational agent. Moreover, TMB of MDM2-amp tumors were significantly lower than that of MDM2-WT and MDM2-mutation (-mut) tumors (median TMB: 3.1 vs. 4.6 vs. 10.8, p < 0.001 respectively). Conclusions: MDM2 amplification was found in 3.3% of 10010 Chinese cancer patients, 83.4% of whom harbored wild-type TP53 that were potentially responsive to MDM2 inhibitors. In addition, 82.8% of the patients with MDM2-amp harbored genomic co-alterations and were potentially therapy targetable. This study provided insights into identifying patients who might potentially benefit from anti-MDM2 therapies.
Association between MUC5B mutation and prognosis across solid tumors.
Authors: Zhao Qun , Zheng Hong , Duan Wei , Li Chengcheng , Xie Wenzhuan , Wang Guoqiang , Zhang Yuzi , Bai Yuezong , Zhou Yingchun 
Published: May 2020

e13515 Background: MUC5B encodes Mucin 5B, which is a gel-forming mucin and a major constituent of mucus in the respiratory tract. Previous studies have revealed an increased expression of MUC5B in invasive mucinous adenocarcinoma (IMA) of the lung, indicating it may be involved in the tumorigenesis, and its family member MUC16, which encodes cancer antigen 125 (CA125), a biomarker for tumor diagnosis and the MUC16 mutation was reported to be associated with higher tumor mutation load, and a better survival outcomes in Gastric Cancer. However, the association between MUC5B mutation and prognosis has never been investigated in solid tumors. Methods: Whole-exome sequencing, RNA sequencing and clinical data for 27 types of solid tumors were downloaded from The Cancer Genome Atlas (TCGA). Associations between MUC5B mutation and prognosis were analyzed, and gene set enrichment analysis (GSEA) was used to investigate the underlying mechanism. Results: Among the 27 tumors, MUC5B mutation was associated with a superior disease specific survival (DSS) in Uterine Corpus Endometrial Carcinoma (UCEC) (HR, 0.32; 95% CI, 0.13-0.80; P = 0.01), Bladder Urothelial Carcinoma (BLCA) (HR, 0.43; 95% CI, 0.18-1.05; P = 0.06) and lung adenocarcinoma(LUAD) (HR, 0.44; 95% CI, 0.2-0.95; P = 0.03). MUC5B was also or tended to be associated with longer progression-free survival (PFS) and overall survival (OS) in UCEC (PFS: HR, 0.40; 95% CI, 0.23-0.70; P < 0.001; OS: HR, 0.57, 95% CI 0.31-1.03, P = 0.06), BLCA (PFS: HR, 0.40; 95% CI, 0.19-0.86; P = 0.02; OS: HR 0.42, 95% CI 0.20-0.90, P = 0.02) and LUAD (PFS: HR, 0.63; 95% CI, 0.38-1.06; P = 0.08; OS: HR 0.55, 95% CI 0.31-0.97, P = 0.04). However, MUC5B mutation was associated with poorer OS (HR 1.64, 95% CI 1.03-2.59, P = 0.03) and tended to be associated with poorer PFS (HR 1.56, 95% CI 0.95-2.57, P = 0.08) in Head and Neck squamous cell carcinoma (HNSC). MUC5B mutation was not associated with survival in other tumors. MUC5B mutation was associated with a higher TMB in UCEC, BLCA and LUAD, and GSEA revealed prominent enrichment of signatures related to DNA repair in MUC5B mutation group, compared to MUC5B wide-type group in UCEC (FDR < 0.05), BLCA (FDR < 0.05), and LUAD (FDR < 0.05), but not in HNSC. Conclusions: MUC5B mutation may be a potential predictor for better prognosis in UCEC, BLCA and LUAD, through potentiating DNA damage repair signaling. Identification of MUC5B mutation by genomic profiling provides a potentially novel and convenient approach for these patients to predict the prognosis, and refines patients' management in clinical practice.
Features of iso-miR expression in colon tumor tissue.
Authors: Timoshkina Natalya N. , Kutilin Denis S. , Novikova Inna A. , Poluektov Sergey I. , Tolmakh Roman E. , Dashkov Andrey V. , Haragezov Dmitry , Kolesnikov Evgeniy N. , Dontsov Vladimir A. , Petrov Dmitry S. , Soldatkina Natalya V. , Kit Oleg Ivanovich 
Published: May 2020

e13518 Background: With the advent of deep sequencing, enormous variability in miRNA biogenesis was detected, which means that many different sequences can potentially be generated from the same miRNA precursor, potentially having different targets and opposite changes in expression. These variable forms of micro-RNA that differ from the reference sequence are called iso-miR. To date, features of iso-miR expression have not been studied in patients with colorectal cancer (CRC). The aim of the study was to analyze the differential expression of iso-miR in the tumor and normal tissues of patients with CRC. Methods: For iso-miR identification by method of multiple parallel sequencing, 18 patients with CRC (colon adenocarcinoma, G2-3) were selected. The mirVana miRNA Isolation Kit protocol (Ambion, Life Science Technologies, USA) was used to isolate small RNA fractions. The library was prepared using the TruSeq Small RNASample Preparation Kit (Illumina, USA). Sequencing of the nucleotide sequences of cDNA libraries was performed using a MiSeq (Illumina, USA). The determination of iso-miR expression was carried out by comparing the nucleotide sequence of the sequenced molecules in each sample with the known nucleotide sequences of micro-RNA presented in the databases. When analyzing the iso-miR differential expression, the DESeq method implemented in R medium was used. Results: Several iso-miR classes were found (exact, lv3p, mv (multiple variant), nta#T#1 (non-templated T addition)). The most represented is the exact class (corresponding to the canonical miRBase sequence) and lv3pE (3 'extended: it starts from the same position as the canonical sequence, but is longer than the canonical sequence). Statistically significant (p < 0.001) differences in the expression of tumor tissue relative to normal were found for hsa-miR-143 (exact), hsa-miR-26a (exact) and hsa-miR-27b (exact) - a decrease in expression in 3, 32 and 6 times respectively, for hsa-miR-10a (lv3p), hsa-miR-10b (lv3p), hsa-miR-10b (mv) - a decrease of 2 times, for hsa-miR-143 (lv3p) - an increase of 2 times, hsa-miR-143 (nta # T # 1) - a decrease of 5 times, for hsa-miR-192 (lv3p) and (nta # T # 1) - a decrease of 16 and 3 times, respectively. Conclusions: Differential expression of 4 iso-miR classes (exact, lv3p, mv, nta # T) hsa-miR-26a, hsa-miR-27b, hsa-miR-10a, hsa-miR-10b, hsa-miR-143 and hsa-miR-192 was found in patients with CRC, which probably can affect the transcriptional activity of the genes they target. These iso-miRs are also likely to act as potential tumor markers.
An analysis of growth in the genetic counseling profession 2009 to 2019.
Authors: Hooker Gillian , Allain Dawn C. , Buchanan Adam H , Care Melanie , Conway Laura , Cumming Alessandra , Dixon Shannan , Paulyson-Nuñez Kristin , Riordan Sara , Williams Janet 
Published: May 2020

e13526 Background: Genetic counselors (GCs) are health care professionals who provide support to patients and physicians navigating the rapidly changing landscape of genetic testing and the genetic underpinnings of disease. Increased demand for genetic counseling services prompted an analysis of changes in the workforce over the last decade. Methods: To quantify the growth in the GC profession in the U.S and Canada in the last decade, we acquired data from the American Board of Genetic Counseling, National Society of Genetic Counselors, Canadian Association of Genetic Counselors, Accreditation Council for Genetic Counseling and Association of Genetic Counseling Program Directors. Results: Between 2009 and 2019, the workforce more than doubled, growing from 2,205 ABGC-certified GCs to 5,172. In Canada, the number of CAGC-certified GCs has grown from 211 in 2009 to 327 in 2019. Growth is striking in cancer genetic counseling; the proportion of GCs providing direct patient care in North America who report cancer as a primary specialty has increased from 25% in 2008 to 50% in 2019. Similar growth has been seen in training opportunities for GCs. The number of accredited graduate programs has increased from 33 in 2009 to 51 in 2019, with several more in development. Combined, these programs had 464 training slots in 2019, up from 223 in 2009. In 2019, 1569 applicants registered for the applicant match for training. Training opportunities and clinical genetic counselors are concentrated in large metropolitan areas, with over half of GCs working in 28 metro regions. GC services in rural areas are increasingly provided remotely via telemedicine, with 59% of GCs in direct patient care in 2018 reporting providing services by phone and 19% using web or video services to deliver care. In cancer genetics, about 50% of GCs nationwide reported in 2018 their 3rd next available appointment for new patients was within 14 days. Conclusions: The past decade has seen significant growth in the numbers of GCs and more patients have access to GCs than a decade ago. Reimbursement for services remains a significant barrier to access. Further research is warranted to understand additional political, administrative and logistical facilitators and barriers to providing care to all who need genetics services.