bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of clinicopathological parameters with outcome in patients with metastatic breast cancer treated with eribulin in South East London.
Authors: Li Su , Agorastos Antonios , Kristeleit Hartmut 
Published: September 2018

e12567 Background: Eribulin is licensed for the ≥2-line treatment of patients with metastatic breast cancer. We assessed outcome of eribulin treatment in real world patients. Methods: We conducted a retrospective analysis of consecutive patients treated with eribulin for metastatic breast cancer at Guys Cancer Centre and affiliated units in South East London between Oct 2011 and Nov 2016. All data was extracted from electronic patient records. Results: We identified 158 patients with a median age of 55.8 years (range 30-94). Median WHO performance status (PS) was 1 (0-4). 68% were of white ethnicity, 23% black and 5% other. 67% were ER+, 13% Her2+ and 26% triple negative breast cancer (TNBC). 96% had visceral disease and 15% of patients had CNS involvement. Eribulin was given in 1% of patients as 1st line, 10% as 2nd, 51% as 3rd, 21% as 4th and 17% as 5thline treatment or beyond. Patients received a median of 4 cycles of eribulin (range 1-35). Median overall survival (OS) was 9.3 months and progression free survival (PFS) 3.4 months. A response was seen in 34% of patients, disease stability in 19%. OS was significantly better for patients > 60 years of age compared to < 60 years (10.3 vs 8.3 months, HR 1.45, 95% CI 1.04-2.10). OS for ER+ was 10.2 vs 7.6 months for ER- and for TNBC. OS for white patients was 9.4 months vs 8 months for black ethnicity. Black patients were younger (median age 50.5 vs 59.9). We observed that amongst TNBC patients black ethnicity had a trend towards longer survival (9.1 months for black vs 7.7 months for white). Due to the retrospective nature of this study toxicity was not well documented. Dose reductions were required in 35% of patients and 3% experienced neutropenic fever. Conclusions: OS was inferior to documented outcome in the EMBRACE trial (9.3 vs 13.1 months). This is despite a lower median number of previous lines of chemotherapy. Our cohort had a poorer baseline PS (20% PS2, 3% PS3 and above vs 8% PS2 in EMBRACE) and a higher proportion of black patients (23% vs 4% in EMBRACE). 15% had known CNS disease. The observation that triple negative patients of black ethnicity fare better than white patients treated with eribulin warrants further exploration.
Outcomes in BRCA1/2 breast cancer patients treated with everolimus followed by chemotherapy+/- PARP inhibitors.
Authors: Soliman Hatem Hussein , Anderson Matthew , Han Hyo S. 
Published: September 2018

e12569 Background: Research demonstrates blocking mTOR signaling can suppress homologous DNA repair pathways. Use of drugs like everolimus can sensitize cancer cells to DNA damaging agents, particularly if they already harbor defects in DNA repair, such as mutations in BRCA1/2 genes. We sought to analyze our Total Cancer Care (TCC) dataset including BRCA1/2 germline mutation carrier patients who were enrolled on a completed randomized phase 2 trial (NCT01506609) of carboplatin/taxol (CT) or temozolimide (TEM) +/- veliparib (PARPi) at Moffitt Cancer Center (MCC). Time on study treatment (TOT) for patients who received everolimus (EVE+) prior to study enrollment was compared to those who did not (EVE-). Methods: We identified MCC patients treated on trial who were TCC consented to provide clinicopathologic and treatment data. Information on prior treatments, EVE exposure, Estrogen receptor (ER) status, unblinded trial treatment if known, and TOT were collected. Summary statistics and comparison of median TOT in EVE+ vs. EVE- pts using a two tail Mann-Whitney test (significance p < .05), and Wilcoxon Signed Rank Test of TOT EVE+ vs. reported PFS of CT+PARPi arm were performed. Results: Fourteen pts (6 EVE+, 8 EVE-) were identified with clinical data described in Table 1. Median TOT for EVE+ = 25.1 mos (95% CI 19.5-29.8), EVE- = 7.4 mos (95% CI 3.9-15.4) with p = .002. EVE+ TOT was significantly higher than median PFS of 14.1 mos for CT+PARPi arm (p = .03). Median TOT on EVE was 4.3 mos (95% CI 2.7-16.3). In EVE+ 5 pts discontinued for progression, 1 for toxicity. In EVE- 5 pts discontinued for progression, 3 for other causes. Conclusions: Significantly better TOT on DNA damaging therapy was observed in a small group of ER+ BRCA1/2 mutated breast cancer pts previously exposed to EVE compared to EVE- pts. This observation requires further study in the entire study population and confirmation in prospective trials with sequenced EVE-CT+/-PARPi for ER+ BRCA1/2 pts. [Table: see text]
Retrospective review of steroid-induced acne in patients with breast cancer.
Authors: Krishnasamy Shalini R , Jung Jae 
Published: September 2018

e12570 Background: With the rapid development of targeted inhibitors, the incidence of cutaneous chemotoxicities is rising and represents a significant cause of morbidity in cancer patients. Therefore, rapid recognition of rashes that warrant dose reduction or discontinuing treatment is critical. Unfortunately, the concomitant use of systemic steroids with chemotherapeutics that can produce acneiform eruptions, make it difficult to distinguish a cutaneous chemotoxicity from systemic steroid induced acne (SSIA). Although SSIA is a well known complication of systemic steroid administration, there are few published studies regarding this condition, none of which have been done in cancer patients. In this study, we sought to examine the incidence of SSIA, the patient and tumor characteristics as well as the chemotherapy regimen most commonly associated with SSIA in breast cancer patients treated with chemotherapy at the City of Hope National Comprehensive Cancer Center. Methods: We performed a retrospective study. Using the institutional registry of patients, we identified 3,848 patients that received a diagnosis of breast cancer between 1/2009-6/2015, 1,991 (51%) of which received at least one cycle of chemotherapy. 61 of these patients received a ICD-9 billing code for “acne” or “ steroid acne”, 10 of whom had explicit documentation of acne or acneiform eruption in their chart. Results: All 10 patients were female with a median age of 49 (range 36-56). 50% of patients had ER+/PR+ disease and 30% had ER-/PR-/HER2- breast cancer. 90% of patients had stage I or II disease. 70% of patients developed steroid induced acne after the 1st cycle of chemotherapy. All regimens contained either docetaxel or paclitaxel. Dexamethasone was implicated in all but one case. We report an overall incidence of SSIA of 0.05% among breast cancer patients treated with at least once cycle of chemotherapy at our institution. Conclusions: These results suggest that breast cancer patients at highest risk for SSIA are on taxane-based regimens with early stage disease and are most likely to develop the reaction after their first cycle of chemotherapy. This study however is limited by the retrospective design, the reliance on ICD 9 billing codes, and the limited sample size.
Safety and efficacy of eribulin in combination with gemcitabine in patients with advanced triple negative breast cancer.
Authors: Michalaki Vasiliki , Fragulidis Georgios , Kondis Ioannis , Karvouni Eleni , Dafnios Nikolaos , Kotsiou Antonia , Vassiliou Ioannis , Papadimitriou Christos 
Published: September 2018

e12578 Background: Triple negative breast cancer (TNBC) characterized by aggressive tumor behavior with very poor prognosis following progression after standard chemotherapeutic regimens.The combination of Gemcitabine, a nucleoside analogue, and eribulin a microtubule-targeting agent exhibited synergistic cytotoxic effects in pre-clinicall and clinical setting . Thus, eribulin combined with gemcitabine may synergistically induce tumor cell death, especially in tumors like TNBC. Based on this rationale, we conducted a phase II study evaluating this combination either in first- or in second-line treatment for advanced TNBC.Methods: Females with locally advanced or metastatic TNBC who had received previous chemotherapy , with an ECOG (PS) ≤ 1, and adequate hematological, renal and hepatic function. Patients received eribulin (1mg/m2) plus gemcitabine (1000 mg/m2) on day 1 and 8, q21 until disease progression. CT scans were performed every 12 weeks. The main objective of this trial was to evaluate the overall response rate (ORR) and secondary were Feasibiliy, safety and clinical benefit rate (CBR ). Results: Thirty –two females (median age: 62 years, median ECOG performance status (PS) 1) were enrolled the study. The majority had visceral disease (78.5%). A median of 9 (range:4–18) treatment cycles was administered (69% of patients received ≥ 6 cycles), .All patients were evaluable for response. We did observe 12 partial responses for an overall response rate of 37.5% (95%CI,26.1-57.0). A stable disease was observed in 15 patients (46.8%). Clinical benefit, was observed in 21 patients (65.6%; 95%CI,48.1-76.6). The most common grade 3 or 4 toxicities were haematologic . The main grade 3 or 4 non-hematolgic toxicities were fatigue, diarrhoea, nausea and vomiting. Of the 32 patients in total 7 patients had dose reductions and 14 patients had dose delays. Conclusions: Resistance to current standard therapieslimits the available options for previously treated patients with metastatic TNBC and there is currently no preferred standard chemotherapy. This study demonstrated that the combination of eribulin and gemcitabine was efficacious, feasible and toxicity was generally manageable
Long term follow up of patients with locally advanced triple negative breast cancer treated with adjuvant high dose chemotherapy and autologous stem cell transplantation: A single center experience.
Authors: Bukari Sani Mohammed , Usman Muhammad , Abrams Judith , Ratanatharathorn Voravit , Uberti Joseph P. , Deol Abhinav , Bhutani Divaya , Alavi Asif , Ayash Lois Jeanne ,   Blood and Marrow Transplant Program, Wayne State University/Karmanos Cancer Institute
Published: September 2018

e12590 Background: Adjuvant high dose chemotherapy (HDC) with Autologous Hematopoietic Stem Cell Transplantation (AuSCT) as part treatment of high risk locally advanced breast cancer has remained controversial. Multiple trials reported disease free survival (DFS) without Overall survival (OS) resulting in its abandonment in early 2000s. However, post hoc analysis of these trials consistently reported DFS and OS benefit in young and triple negative breast cancer (TNBC) subgroups. This has not been re-evaluated till date. Recent European registry reports coupled with improved transplant related mortality (TRM) and still poor out-come of standard of care in TNBC subgroup has generated renewed interest. We report long term out-come of locally advanced high risk TNBC treated with HDC and AuSCT treated in Karmanos Cancer Institute from 1995 to 2001 Methods: Majority of the patients were treated with Adriamycin and Taxane based induction chemotherapy. Patients without evidence of metastatic disease proceeded to HDC and AuSCT using Carmustine 600mg/sqm Cyclophosphamide 5.6gm/sqm and Cisplatin 165mg/sqm (STAMP 1 regimen). This is followed with loco- regional radiation per protocol. Results: 72 hormone negative patients with Lymph Node(LN) > 4 or inflammatory breast cancers were selected from 576 treated for advanced or metastatic breast cancer. 33 patients were TNB with HER2 status of 39 patients unknown. Median time from diagnosis to stem cell transplantation was 6 months. Median age at diagnosis was 47yrs. Mean LN involvement was 9 with 90% having (4-20) LN positivity. With median follow up of 16 years,10yrs DFS and OS were both 62.5%. Median follow up for DFS and OS was not reached.TRM was 9% mostly from pulmonary toxicity. Conclusions: This study of locally advanced high risk TNBC treated with adjuvant HDC and AuSCT have high 10yr OS of 62.5% compared to current standard of care. With the current improvement in TRM, reevaluation of this strategy through clinical trials in this subgroup whose outcome remain poor is reasonable.
Risk evaluation about genetic screening among ovary cancer with regard to Lynch syndrome.
Authors: Kim Min Kyu 
Published: September 2018

e13000 Background: Hereditary cancer syndrome about ovary cancer is mostly BRCA related. But mismatch repair genes related Lynch syndrome is also associated with it.There is not much study about risk evaluation about this among Korean population. We investigate this. Methods: A retrospective review of ovary cancer patients who was counseled about Lynch syndrome in Department of Obstetrics and gynecology, Samsung Changwon Hospital by single surgeon was done. Clinical information was extracted from the medical record including age, family and personal history of cancer, immunohistochemistry (IHC) of MLH1/MSH2, microsatellite instability test (MSI). Results: Total test was 26.mean age was 54(16~75) and fifty percent was serous type (13/26).There were 2 patients with Lynch syndrome related cancer family history (stomach and ovary) among their 1st degree relatives. Only one patient has abnormal MLH1 IHC.There were three unstable MSI patients (BAT26, D2S123, D55346, and NR21). Conclusions: We found three abnormal MSI patients among this population. Cost effective algorithm using multiple genetic testing to find Lynch syndrome associated ovary cancer patients should be developed through large population study.
A novel approach to detect large indels from targeted sequencing data in clinical cancer setting.
Authors: Chen Lijuan , Chen Caiping , Chen Dongling , Zou Qiuyi , Qin Gungwei , Kang Hui , Yao Ming , Wang Kai 
Published: September 2018

e13002 Background: Next generation sequencing (NGS) technologies have already shown numerous advances to revolutionize our understanding of cancer genomic profiling and improve cancer treatments. There have been many NGS data analysis tools available for identification of different genomic alternations including short insertion and deletion (short indel, < 25 bp in general). However, detection of > 100 bp large indel (L-indel) from short reads (generally < 200 bp) remains a huge challenge. L-indels identified in genes like MET and FLT3 have proven a critical implication in cancer treatments. Moreover, there is an urgent need for an algorithm to validate L-indels generated by genomic modification systems like ZFN, TALENs and CRISPR/Cas9. Methods: A novel algorithm was developed for calling L-indels in targeted sequencing data as following: raw reads were first filtered by selecting high-quality ones and correcting wrong bases; a chunk of contig (unitig) was then assembled and aligned to reference genome; lastly, break point information was collected and L-indels were calculated. The algorithm was applied on the reads generated from NA12878 cell line and FFPE samples collected in our lab respectively on the Illumina platform. Validation were performed by PCR and Sanger sequencing. Results: 22 novel exonic L-indels (17 deletions and 5 insertions) were identified with a median size of 1,616 bp (range: 25-6,684 bp) from NA12878 sequencing data and 100% successfully confirmed by Sanger sequencing. In addition, 6 out of 9 reported L-indels were also found with the rest awaiting for further exploration. Strikingly, a 2,446 bp deletion on MSH6, encodes an important component in mismatch repair (MMR) system, was detected on a FFPE sample of a lung cancer adenocarcinoma, which prompted to consideration of MMR deficiency otherwise. Conclusions: We have developed and validated a novel and accurate method for NGS large indels detection dedicated for targeted sequencing data in clinical cancer setting. Equipment of this method will greatly increase the capability of comprehensively understanding genomic alterations from a single NGS-based assay, and provide more information for potential clinical use.
Identification of genes with clonal mutations for the tumorigenesis of breast cancer subtypes.
Authors: Cheung Yee Him , Wu Jie , Dimitrova Nevenka 
Published: September 2018

e13006 Background: Current analyses on somatic mutations mainly involve counting samples as either carriers or non-carriers. Such a binary approach misses to take into account the fraction of tumor cells that carry a mutation, which is a significant measure of the influence of a mutation on the overall phenotype, such as gene expressions, subtype and pathway activity. Methods: In this study, we re-analyzed the 72,084 non-synonymous somatic mutation in 16,164 genes of 817 TCGA breast cancer samples (HER2+: 65, Luminal A: 415, Luminal B: 176, Basal: 136 and Normal-like: 25) using variant allele frequency (VAF) adjusted by sample purity derived from multiple methods. We obtained a gene-based VAF by choosing the maximum VAF among all mutations found in each gene for each sample. For each breast cancer subtype, we filtered for top 100 genes with highest number of mutation carriers and then ranked them by decreasing average VAF across all samples. We assume genes with higher average VAF are more likely to harbor clonal mutations in early tumor progression. We further evaluated the Pearson correlation between VAF of genes having at least ten mutation carriers and the expression levels of ESR1, PGR and ERBB2 in Luminal A subtype. Results: The top two genes with highest VAF for each of the four subtypes are as follows: (a) HER2+: ERBB2 (VAF = 0.39 ± 0.21, n = 4), KAT6A (0.31 ± 0.09, 4), (b) Luminal A: CTCF (0.41 ± 0.19, 13), MAP2K4 (0.37 ± 0.14, 24), (c) Luminal B: MAP2K4 (0.46 ± 0.11, 5), TP53 (0.46 ± 0.17, 64), and (d) Basal: SCN10A (0.46 ± 0.29, 5), MYH9 (0.43 ± 0.16, 5). The strongest correlations for Luminal A are: (i) SPEN (corr. = 0.85, n= 14), KMT2C (0.73, 24) and DMD (0.73, 11) with ESR1, (ii) DMD (0.69, 11) and NBL1 (0.67, 10) with PGR, and (iii) TBX3 (-0.51, 12) and MUC12 (0.47, 14) with ERBB2. Conclusions: While carrier count is effective for identifying genes prone to mutations, average VAF opens another perspective for uncovering genes that tend to harbor clonal mutations. Our work shows the potential of VAF analysis for identifying driver genes, understanding tumor progression and evaluating the impact of a mutation on a patient. As future work, we may improve the VAF estimates by adjusting for copy number variations and weight each variant by pathogenicity.
MFN2 might be a risk factor for lung adenocarcinoma.
Authors: Lou Yuqing , Zhang Yanwei , Xu Jianlin , Gu Ping , Zhang Wei , Zhang Xueyan , Zhong Hua , Jiang Liyan , Han Baohui 
Published: September 2018

e13007 Background: Genetic mutations in Mitofusin-2(MFN2) interrupt mitochondrial fusion and cause the untreatable neurodegenerative condition Charcot-Marie-Tooth disease type 2A( Nature, December 2016). MFN2 was initially identified as a hypertension-associated gene and implicated in the pathogenesis of multiple cancer types. However, underlying mechanisms of MFN2 in lung adenocarcinoma was unclear. Methods: MFN2 expression at protein level was examined in 30 pair lung adenocarcinoma/adjacent normal lung samples with immunohistochemistry staining. Then MFN2 knocked down in human lung adenocarcinoma cells A549 with lentiviral-mediated shRNA strategy. The effects of MFN2 knockdown on cell proliferation, cell cycle process, cell migration and invasion was investigated in A549 cells. MFN2-knockdown induced gene expression changes was analyzed by microarray assay and then functional pathway enrichment analysis was performed to identify critical pathways involved in MFN2-mediated lung adenocarcinoma development. The expression changes of downstream factors were determined by western blot. Furthermore, tumor models in nude mice were generated. Tumor formation and progression in these mice were analyzed. Results: As compared to adjacent normal lung tissues, MFN2 expression was significantly higher in lung adenocarcinoma tissues with positive MFN2 signals in 90% (27/30) lung adenocarcinoma tissues and only in 26.7% (8/30) adjacent normal tissues. Furthermore, MFN2 knockdown inhibited cell proliferation, induced cell cycle arrest and blocked invasion behavior in A549 cells. MFN2-knockdown induced gene expression changes in A549 cells was analyzed by microarray assay. Functional pathway enrichment analysis revealed that 6 pathways were enriched in deregulated genes including Cell cycle, DNA replication, ECM-receptor interaction, Focal adhesion, MAPK signaling pathway and Chemokine signaling pathway. Downregulation of RAP1A and upregulation of RALB and ITGA2 identified in MFN2-knockdown cells by microarray analysis were confirmed by western blot. In vivo, tumor formation and progression in nude mice showed that MFN2 knockdown reduced tumorigenesis of A549 cells. Conclusions: MFN2 overexpression run a risk of lung adenocarcinoma.
Effectiveness of tablet family history collection in a multidisciplinary pancreatic tumor clinic in identifying patients with risk factors for hereditary cancer.
Authors: Everett Jessica , Schradle Kara , Cameron Heather , Patel Anisha , Koeppe Erika , Stoffel Elena Martinez , Simeone Diane M. 
Published: September 2018

e13020 Background: A substantial percentage of patients with pancreatic adenocarcinoma (PDAC) harbor pathogenic germline variants in known cancer risk genes, some with relevance for treatment options. Robust collection of relevant personal and family cancer history risk factors for all patients with PDAC is needed to optimize identification of those who could benefit from genetic counseling and testing (GC/GT). Methods: 464 adult patients (≥18 years of age) presenting to a multi-disciplinary pancreatic tumor clinic were invited to complete a tablet based family cancer history survey prior to their clinic appointments. Standard family history entry into electronic medical record (EMR) was reviewed for comparison. Eight GC/CT referral criteria were developed based on existing guidelines for known syndromes associated with PDAC, reported findings from studies of GC/GT outcomes in patients with PDAC, and expert opinion. Presence of any of the 8 criteria were documented for both tablet and EMR collection methods in the subset of patients with PDAC (n = 230). Results: Completion rate for the tablet survey was high (87%). 78% of users completed the survey in ≤15 minutes (x̄ = 12 minutes). 202 patients with PDAC (88%) completed the tablet survey, and 100 (50%) met ≥1 GC/GT criteria. Most frequent criteria identified were: ≥2 relatives with related cancers (28%); ≥1 relative with PDAC (12.9%); personal history of related cancer (12.9%). Tablet data collection improved identification of relatives with breast cancer ca < age 50 from 1.5% to 5.5% due to missing ages at diagnosis in the EMR. The tablet survey also identified 12 patients with Ashkenazi Jewish (AJ) ancestry (6%), a risk factor not accounted for in EMR. Conclusions: Tablet based family cancer history collection is well accepted by patients and easily integrated into clinic work flow. The tablet survey found GC/GT criteria in 50%, and improved identification of key risk factors for BRCA1/2 mutation (AJ ancestry, relative with breast ca < age 50). Further work should focus on integration of tablet based survey data into EMR, and decision support tools to optimize referral and follow through with genetic services.