bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pilot trial of chidamide, an oral histone deacetylase (HDAC) inhibitor, in combination with exemestane in hormone receptor-positive advanced breast cancer.
Authors: Zhang Qingyuan , Wang Tao , Geng Cuizhi , Zhang Yue , Zhang Jinwen , Ning Zhi-Qiang , Jiang Zefei 
Published: September 2018

e12543 Background: Chidamide (CHI) is a novel benzamide type of subtype-selective histone deacetylase inhibitor approved in China for refractory and relapsed peripheral T-cell lymphoma with a dosage of 30 mg PO twice a week. A randomized, double blind and placebo-controlled phase 3 clinical trial of CHI plus exemestane (EXE) is currently ongoing in patients (pts) with hormone receptor-positive (HR+) advanced breast cancer (ABC). This abstract reports the results from the pilot study preceded the phase 3 trial. Methods: Eligible pts were postmenopausal women recurrent or progressed to at least one endocrine therapy. In the run-in period for pharmacokinetic (PK) analysis, pts received EXE 25 mg on day (D) 1 and CHI 30 mg on D 2. From D 5 pts started combination treatment having EXE 25 mg daily and CHI 30 mg twice a week until progression of disease (PD) or intolerable toxicities. A treatment cycle was defined as 28 days. Safety, PK parameters and preliminary efficacy were assessed. Results: 20 pts with HR+ and HER-2 negative were enrolled between Jul and Dec, 2015. Median duration of treatment was 5 cycles (range 0-16), with 4 pts still on treatment. 3 pts discontinued due to adverse events (AE). Drug-related AEs ≥ grade 3 in 2 or more pts were neutropenia (35%), thrombocytopenia (30%), and leucopenia (20%). Similar plasma exposure of EXE was observed in the absence and presence of CHI ( 73 ± 27 vs. 80 ± 29 ng·hr/mL). A potential increased plasma exposure of CHI was noted in the presence of EXE compared with CHI alone ( 2232 ± 973 vs 1787 ± 946 ng·hr/mL), apparently related to the inter-patient variations in CHI plasma concentrations. Best response in 18 pts was assessed by RECIST, including 3 pts with partial response, 12 pts with stable disease and 3 pts with PD. Median progression free survival was 7.6 months. Conclusions: The combination of CHI and EXE was generally well tolerated. Most AEs were related to the CHI single-agent treatment that are generally manageable. Encouraging antitumor activity was observed. The overall results from this pilot trial enabled the next-stage clinical development of this combination regimen in HR+ ABC pts. Clinical trial information: NCT02482753.
Review of next generation sequencing outcomes in patients with metastatic breast cancer.
Authors: Kang Irene , D'souza Anishka , Spicer Darcy V. , Russell Christy Ann , Lang Julie E. , Nelson Maria , Silberman Howard , Lu Janice M. 
Published: September 2018

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.
Multicenter study of the evaluation of eribulin (E) use in Sicily in metastatic breast cancer (MBC): A prospective registry (VESPRY trial).
Authors: Adamo Vincenzo , Ricciardi Giuseppina , Giuffrida Dario , Scandurra Giuseppa , Russo Antonio , Blasi Livio , Spadaro Pietro , Lucenti Antonio , Soto Parra Hector J. , Savarino Antonino , Ferraú Francesco , Zerilli Filippo , Verderame Francesco , Butera Alfredo , Franchina Veronica , Cottini Lorenzo , Fedele Guido , Caruso Michele 
Published: September 2018

e12565 Background: Eribulin Mesylate is a non taxane microtubule dynamics inhibitor, approved for heavily-pretreated MBC patients (pts). Methods: This is a multicenter, prospective, single arm study for E-treatment of third line in pretreated MBC pts, conducted in 14 oncology centers in Sicily. All pts had received two previous chemotherapy regimens for MBC. Pts received E at 1.23 mg/m2 on days 1,8 every 3 weeks until progression. Primary Endpoints: overall response rate (ORR) according to the site of metastases and safety. Secondary objectives: Progression-free survival (PFS) and ORR according to different subtypes. PFS curve was estimated using the Kaplan-Meier method. Multivariable logistic regression model were used to evaluate the associations of each variables with tumor response. ORR was assessed according to RECIST 1.1 and safety with CTCAE v4.0. Results: 122 pts were enrolled and received at least 1 dose of E. Median age was 58 (range 29-79). All received previously anthracycline and taxane based-therapies. Subtypes: Luminal A 69%, Luminal B 7%, HER2 enriched 4% and Triple Negative 20%. The most common metastatic sites were bone and liver; 67% had metastatic disease involving two or more organs. A median of 5 cycles of E (range 1-26) was administrated. 106/122 pts were evaluable for efficacy, all for safety. ORR was 48%. Exploratory subset analysis showed significantly higher ORR in the lung, liver and bone lesions compared to other site of metastases and in HER2 negative pts. Multivariable regression model showed that HER2 positive subtype was correlated with a poor response (odd ratio 6.7, 95% CI 1.2-36.5). The median PFS was 14.7 months (mos) (95% CI 7.2–25.7). Among pts with < 65 and ≥ 65 years, the median PFS was 14.7 and 25.7 mos, respectively. Most common toxicities: G2 diarrhea 1%, asthenia G1 4%, G2 neutropenia 6%, G1 neurotoxicity 5%, QT prolongation 1%, G4 mucositis in only one case. Conclusions: This study showed a significant improved of PFS with E in third line setting and a favorable safety profile compared with results reported in the pivotal trial. Our findings suggest that E has substantial antitumor activity when used early for the treatment for MBC with acceptable safety.
Do the efficacy of BP-C1 correlate to receptor status in patients suffering from metastatic breast cancer stage IV?
Authors: Larsen Stig Einride , Butthongkomvong Kritiya , Sorraritchingchai Sirikul , Sangsaikae Isaraporn , Manikas Alexey , Trishkina Ekaterina , Matrosova Marina , Poddubuskaya Elena 
Published: September 2018

e12581 Background: Cis-coordinated complexes of platinum(II) with polymer of benzene polycarboxylic is currently evaluated in clinical trials for treatment of metastatic breast cancer (MBC) patients. The RECIST was used for evaluation of the target lesions and the sum diameter of the five largest target lesions was measured. BP-C1 inhibits tumor growth, improves quality of life with only few mild to moderate adverse events. The aim was to investigate the correlation between the efficacy of BP-C1 and the receptor status of Estrogen (ER), Progesterone (PR) and Human epidermal growth factor (HER-2) Methods: The material consists of prospectively collected results from 30 Thai and 30 Russian MBC patients included in two randomized and double-blinded controlled clinical trial with stratified semi-cross-over design. The patients received daily IM injections of 0.035mg/ml bw BP-C1 for 32 days. The results from Russia available by March 2017, and will be included in the final presentation Results: Negative ER recorded in 13 patients and positive in 15. During 32 days of BP-C1 treatment, the sum lesion diameters reduces with 1.9 % in the negative receptor group, but increases with 8.0 % among the positive. Similar pattern also detected regarding the PR. Negative PR detected in 17 patients and positive in 12. No changes (0.1%) in the sum lesion diameter found in the group with negative PR, but an increase of 8.8% in the positive group. Negative HER-2 receptor recorded in 13 patients and positive in 13. The sum lesion diameter increases with 7% in the negative group and 6.0% in the positive. In five patients, all the three receptors were positive, 10 patients had one negative receptor, 12 had two negative and three were triple negative. During the 32 days of BP-C1 treatment, the sum lesions increases by 20.7% in the triple positive group and by 7.6% in the group with one negative receptor. In the patients with two or three negative receptors, the sum lesion diameter was unchanged; -0.6% and 0.5%, respectively. The reduction sum lesion diameter seem to increase with increasing number of negative receptors. Conclusions: These findings indicate that BP-C1 may be an important treatment of stage IV MBC with negative ER, PR or HER-2 receptor.
Triple negative breast cancer: An Indian problem— Experience from a tertiary care oncology centre.
Authors: Gupta Sameer , Paryani Jeetendra , Chaturvedi Arun , Kumar Vijay , Akhtar Naseem 
Published: September 2018

e12583 Background: Breast cancer is a heterogeneous disease with distinct biological subtypes as determined by gene expression profiling studies. Breast cancer is most common cancer in Indian females and is believed to be biologically different from west, notably in terms of high prevalence of Triple negative subtype (TNBC). Reliable data on clinical and epidemiological profile of TNBC in Indian population is scarce. Aim of this study was to analyze the epidemiological and clinical profile of TNBCs Methods: Data of 355 patients of breast cancer registered in our department between 2013 and 2015 and followed up until December 2016 was collected and reviewed for epidemiological and clinical features Results: Of total 355 patients analysed, TNBC group was most common (n = 152) (43%) followed by Luminal A (25%). Median age at disease presentation in TNBC was 42.4 years compared to overall age of 45.3 years (24–73 years). In TNBC subgroup, 48% patients presented in locally advanced and 15% in metastatic stage, more commonly in pre-menopausal patients. Overall 268 (76%) patients underwent surgery with Modified radical mastectomy being preferred surgical option (86%), followed by adjuvant chemotherapy. TNBC subgroup demonstrated low response rate to neoadjuvant chemotherapy with only 9% of patients having complete response and 25% patients having progressive disease. Median followup was 34 months (6 50 months). Of the total recurrences (n = 19), nearly 2/3rd (n = 13) were documented in TNBC subgroup. Disease free survival (DFS) of TNBC subgroup was lower than of other luminal subtypes (p = .043) Conclusions: TNBC was the most common breast cancer subtype (43%) in Indian population which is nearly twice the rate reported in Western countries. This finding has significant clinical relevance as it may contribute to poor outcomes in Indian patients. Our study also corraborated this fact with higher prevalence of premenopausal breast cancer, poor response to neoadjuvant chemotherapy, high recurrence rates and decreased disease free survival. Additional research is needed to understand the determinants of TNBC in India as it is a prognostic group with aggressive behaviour that commonly lack the benefit of any specific targeted therapy
Triple-NOTE (Triple Negative Outcome in ESME): Large recent real-world prognostic data on triple negative metastatic breast cancers (mTNBC).
Authors: Sablin Marie-Paule , Tchokothe Corinne , Loirat Delphine , Bachelot Thomas Denis , Fourme Emmanuelle , Carton Matthieu , Mokdad-Adi Meriem , Berchery Delphine , Levy Christelle , Jacot William , Penault-Llorca Frederique Madeleine , Goncalves Anthony , Vanlemmens Laurence , Eymard Jean-Christophe , Campone Mario , Simon Gaetane , Robain Mathieu , Cailliot Christian , Le Tourneau Christophe , Ricci Francesco 
Published: September 2018

e12592 Background: During last decade, therapeutic arsenal has expanded for metastatic breast cancer (mBC), but few data are available about mTNBC, a poor prognosis subtype. In 2014, UNICANCER (composed of 18 French Comprehensive Cancer Centers) launched the Epidemiological Strategy and Medical Economics (ESME) program to centralize real-world data. This base represents a great opportunity to update the outcomes and the treatment practice patterns of this population. Methods: The ESME-mBC database was built from information systems, treatment databases and patients’ electronic files including quality control processes. All pts who initiated treatment for mBC between 01-Jan-2008 and 31-Dec-2014 were selected. The primary objective of this study was to assess overall survival (OS) of mTNBC pts. TNBC status was defined as ER and PR < 10% in both primary and metastatic disease, as well as the absence of overexpression or amplification of HER2. The secondary objectives were to describe the characteristics of this population, clinical management (duration and sequence of treatments) and to evaluate the prognostic value of several clinical factors (age, distant disease free interval, location and number of metastatic sites) Results: Among 16703 pts in the ESME-mBC database, 2368 (14%) had mTNBC. Median OS over this time period was 14.8 months (95% CI 14-15.6). Median age at diagnosis of mBC was 57 years. For the pts who relapsed, median metastasis free interval was 24 months, while 25.5% of the pts were de novo metastatic. 61% of the pts presented visceral metastasis and 12% had cerebral metastasis as first metastatic site. The pattern of metastatic involvement (visceral and cerebral) and a short metastasis free interval ( < 24 months) were the most important prognostic factors in multivariate analysis. The description of treatment sequences (duration, prognostic value) will be presented. Conclusions: In this real-life setting database, mTNBC remain of poor prognosis despite a trend for a better OS than the historical data available (12-13 ms). This TNBC ESME cohort is one of the largest available and offers an updated assessment of the outcomes of this population.
Genetic counseling to outpatient cancer population.
Authors: Ce Coelho Juliano , Trasel Henrique de Araujo Vianna , Koech Bruno Lopes , Oliveita Netto Cristina , Azevedo Sergio J , Ashton-Prolla Patricia 
Published: September 2018

e13009 Background: Recent advances in genetics and molecular biology have made possible to define the hereditary risk of certain diseases. About 10% of cancer are due to a hereditary syndrome and increasing access to genetic testing allows us to identify people or families at risk. Methods: A multidisciplinary team composed of clinical oncologists and geneticists retrospectively evaluated all cancer patients referred to the outpatient clinics of the Hospital de Clínicas de Porto Alegre Cancer Center between October 1st, 2014 and July 31st, 2015. Epidemiological data, pathological examination and family history of cancer recorded in the electronic database at the first visit to the oncologist were analyzed. Results: A total of 708 patients were analyzed. 44 (6.21%) patients were identified and referred for genetic evaluation by the clinical oncologist. Another 85 (12.0%) patients were identified by the multidisciplinary team, completing a total of 129 (18.22%), patients that should be evaluated to the presence of a hereditary syndrome. 164 (23.16%) patients could not be evaluated by the multidisciplinary team because insufficient data were recorded especially those related to family history of cancer. The main diagnosis that indicated genetic evaluation were colorectal cancer (47 cases - 36.43%), breast cancer (36 cases - 27.90%) and ovarian cancer (8 cases - 6.20%). Conclusions: A multidisciplinary evaluation of the oncologic patient is mandatory. Few patients are referred to a genetic counseling and 1 out of 4 patient could not be evaluated because there was missing data in the medical records. A precise genetic evaluation can identify patient / families at risk to develop cancer, allowing the development of cancer prevention strategies in this high-risk population.
Prevalence of BRCA1/2 mutations among an Irish cohort unrestricted by testing eligibility thresholds.
Authors: Conroy Michael , Gallagher David James , Farrell Michael P. 
Published: September 2018

e13013 Background: Diagnostic criteria for BRCA1/2 genetic testing vary worldwide. Different eligibility thresholds for testing are used in different healthcare systems. In the public system in Ireland, this threshold is based on the Manchester Score (MS), with a score of ≥16 (approximately 10% likelihood of BRCA1/2 mutation) required for testing. Individuals unaffected by cancer are not eligible for diagnostic testing. Testing is also available privately by self-paying. We reviewed all self-pay patients in Ireland who were unrestricted by national guidelines. Methods: We performed a retrospective chart review of results from BRCA1/2 genetic testing in the Mater Private Hospital genetics clinic. Outcomes were recorded as ‘positive’, ‘wild type’ or ‘variant of uncertain significance’ (VUS). Results: 276 patients underwent testing between 2011 and 2016. 203 were affected with a median age of diagnosis of 48 (range 14-76), and 73 were unaffected individuals with a median age of 45 (range 30-74) at testing. 103 affected patients had a MS of ≥ 16: 7(6.8%) tested positive for BRCA1 mutation and 11(10.7%) tested positive for a BRCA2 mutation. Seven (6.8%) had a VUS characterised. 100 affected patients had an MS of <16: 3(3%) tested positive for a BRCA1 mutation and 5(5%)tested positive for a BRCA2 mutation. Eight (8%) had a VUS identified. 39 unaffected individuals had a MS ≥ 16: 6(15.4%) tested positive for a BRCA1 mutation, and 1(2.6%) for a BRCA2 mutation. 5(12.8%) had a VUS. 34 unaffected patients had an MS of <16: 2 (5.8%) tested positive for a BRCA2 mutation and 1 (2.9%) had a VUS. A total of 134 patients had a MS<16, and the prevalence of BRCA1/2 mutation in this group was 7% (n=10). Conclusions: The mutation detection rate was higher than expected in unaffected individuals and individuals belonging to families with MS < 16. Scoring systems such as the MS help to prioritise resources but miss many BRCA1/2 mutation carriers. [Table: see text]
Clinical actionability of germline testing in patients with limited colorectal polyps.
Authors: Rohanizadegan Mersedeh , Aldubayan Saud H , Giannakis Marios , Mu Xinmeng Jasmine , Nishihara Reiko , Qian Zhi Rong , Nowak Jonathan , Cao Yin , Liu Li , Song Mingyang , Chan Andrew T. , Garraway Levi A. , Ogino Shuji , Fuchs Charles S. , Van Allen Eliezer Mendel 
Published: September 2018

e13027 Background: As classic adenoma-carcinoma sequence is the main process underlying most colorectal cancer (CRC), early detection and removal of colorectal adenomas is crucial in preventing CRC. Although adenomatous polyps are usually sporadic, several inherited CRC syndromes such as Familial adenomatous polyposis, MUTYH-associated polyposis and Lynch syndrome can present initially with colon polyps. The identification of germline defects in patients with colon polyps is thus critical for proper cancer risk counseling and CRC prevention. Current guidelines recommend germline testing for patients with more than 20 polyps or those with more than 10 polyps and a family history of CRC. However, the diagnostic yield of germline testing on otherwise healthy individuals with 10 or fewer colon polyps has not been well studied. Here, we performed a pilot study to evaluate the clinical actionability of germline genetic testing on these patients. Methods: A total of 13 cancer-free adults, who presented with colon polyps (n < 10) and who otherwise were not selected based on age of onset or family history underwent germline Exome Sequencing. Variants in 13 well-established CRC risk genes ( APC, CHEK2, MYH, MLH1, MSH2, MSH6, PMS2, NTHL1, BMPR1A, SMAD4, PTEN, STK11, TP53) were evaluated for pathogenicity. Results: A total of 13 patients (12 male, 1 female) were evaluated. The median age of presentation was 69 (range 49 to 88). The median number of adenomatous colon polyps was 1 (range 1 to 8). Two (15.4%, 95% CI = 1.9 - 45.4, Binomial Exact) patients had at least one disruptive mutation in the examined genes. One of these patients had a truncating mutation in APC (p.Arg216*) and presented with two tubulovillous adenomas at age 49. The second patient had 8 adenomas in distal colon and rectum at age 64, and harbored a known pathogenic mutation in MSH6(p.Arg1035*). Conclusions: This pilot study provides evidence that a relatively high percentage of patients presenting with a few colon polyps may have inherited defects in highly actionable genes. If validated in larger cohorts with appropriate population controls, these findings may influence the clinical care of such patients and their families and suggest germline molecular testing in those patients.