bluuebunny/crossref_metadata_2025_split huggingface dataset:
CA 15-3 elevation in U.S. women without breast cancer.
Authors: Hu Xiao , Cao Yu 
Published: May 2020

e13609 Background: Cancer antigen 15-3 (CA 15-3) is an epitope of Mucin 1 transmembrane glycoprotein, used to monitor response to therapy in metastatic breast cancer. Elevated CA 15-3 levels have been noted in other malignant and non-malignant conditions. This is the first population-based study examining CA 15-3 elevation in US women without breast cancer. Methods: Women without breast cancer were identified from the National Health and Nutrition Examination Survey 2001-2002 with CA 15-3 measurements via Meso Scale Discovery immunoassay. CA 15-3 levels were dichotomized per previously reported cutoffs of 20, 25, 30, and 40 U/ml, and also logarithmically transformed. Logistic and linear regression models were used to examine associations between CA 15-3 and demographic characteristics, gynecologic/reproductive history, inflammatory markers, non-malignant chronic conditions and non-breast malignancies. Results: Of 2432 women ages 20-85 (mean 48) years old, eighty (3.3%) had CA 15-3 ≥30 U/ml. Based on cutoff ≥30 U/ml, univariate logistic regression showed ages 40-59, uterine fibroids history, and salpingectomy history were associated with normal CA 15-3; Mexican American ethnicity and increasing C-reactive protein were associated with elevated CA 15-3. Multivariate logistic regression confirmed that only ages 40-49 (OR = 0.162, p = 0.0013) and uterine fibroids history (OR = 0.216, p = 0.0373) remained significantly associated. Similar results were found using other cutoffs. Univariate linear regression showed ages 40-59, salpingectomy history, and longer oral contraceptive pill (OCP) use correlated with lower CA 15-3; Black ethnicity, increasing ferritin, endometriosis history, and lung cancer history correlated with higher CA 15-3. Multivariate linear regression revealed significant associations: ages 50-59 (17.1% lower CA 15-3 vs ages < 40, p = 0.028); race other than White, Black, Hispanic, Mexican (32.0% lower CA 15-3 vs White, p = 0.039); longer OCP use (14.0% lower CA 15-3 for 2-5 yrs’ OCP use, p = 0.023; 21.0% lower for > 10 yrs’ OCP use, p = 0.006; vs OCP use < 2 yrs); endometriosis history (22.9% higher CA 15-3 vs no history, p = 0.051). CA 15-3 levels were not significantly associated with chronic liver conditions, coronary artery disease, or metabolic conditions (elevated BMI, diabetes, hyperlipidemia). Conclusions: Perimenopausal women, uterine fibroids history, and longer OCP use were associated with lower CA 15-3 levels, while non-White ethnicity and history of endometriosis were associated with higher CA 15-3. These findings help to elucidate interpretation of CA 15-3 in clinical practice.
Disparities in cancer premature mortality in Brazil: Predictions up to 2030 and sustainable development goals.
Authors: De Camargo Cancela Marianna , Borges Lopes de Souza Leonardo , Leite Martins Luis Felipe , Correa Schilithz Arthur , Souza Dyego , Hanly Paul , Barchuk Anton , Soerjomataram Isabelle , Sharp Linda , Pearce Alison 
Published: May 2020

e13614 Background: Premature mortality affects the economy directly due to the loss of productivity of individuals who decease, thus ceasing to contribute economically to the country. The 1/3 reduction in premature mortality (30-69 years) from chronic noncommunicable diseases is goal 3.4 of the UN Sustainable Development Goals (SDG). Although cancer is a chronic disease, it comprises more than 100 different conditions, with different risk factors and prognosis. This study aimed to calculate current and predicted premature mortality by 2030 for Brazil and regions, compare with SDG 3.4 target and identify regional progress and future needs. Methods: Mortality data were extracted from the National Mortality Information System of Brazil (SIM) and subsequently corrected for ill-defined causes. Crude and age-standardized mortality rates per 100,000 inhabitants were calculated. NordPred package by software R was used to calculate predictions up to 2030 and compared with the goal of 1/3 reduction of premature deaths. Results: Comparison of observed (2011-2015) and predicted (2016-2030) mortality rates show a 12.0% reduction in the likelihood of death among men and 4.6% among women nationally. Although predicted rates for 2026-2030 are lower than those observed in 2011-2015 predicted number of deaths increases by 75,341 for men and 90,513 for women. Lung cancer mortality rates are predicted to decrease more among men than women, while colorectal cancer mortality will increase for both sexes. Conclusions: The profile of cancer premature mortality is diverse in Brazil. Nationally, only male lung cancer will be close to reaching SDG 3.4 target, endorsing government’s long term efforts to reduce tobacco consumption. Colorectal cancer mortality increases in most regions, reflecting the epidemiological transition. Despite progress in cervical cancer control, it will continue to be a major challenge, especially in the North and Northeast. Our results provide a baseline for public policies for both prevention and access to treatment to reduce premature mortality in Brazil. Differences in cancer patterns show the need to plan and to adapt regionally for each reality.
Mortgage discrimination and breast cancer survival among older women in the United States.
Authors: Beyer Kirsten M. M. , Zhou Yuhong M. , Laud Purushottam W. , McGinley Emily , Yen Tina W.F. , Nattinger Ann B 
Published: May 2020

e13615 Background: Although racism and racial residential segregation are widely considered to contribute to health disparities, including in breast cancer, studies examining the impact of mortgage discrimination, a factor contributing to residential racial segregation, and breast cancer survival are limited. The objective of this study is to examine the relationship between redlining (mortgage discrimination based on property location) and survival among older women with breast cancer. Methods: Using the Home Mortgage Disclosure Act (HMDA) database, we estimated redlining for all census tracts in the Metropolitan Statistical Areas (MSAs) within 15 Surveillance Epidemiology and End Results (SEER) areas. This measure was linked by tract with a SEER-Medicare cohort of 27,516 women aged 66-90 years with an incident stage I-IV breast cancer in 2007-2009 and claims information through 2014. We used cox proportional hazards regression models with survival time as the outcome variable and a 4-level categorical logged redlining variable as the key predictor. We also modeled the hazard ratio using redlining as a continuous variable. Models were stratified by stage, ER/PR status, and age group and adjusted for comorbidity and MSA-level standard error. Results: At a median follow-up of 72 months, one-third of the cohort was deceased. The majority of the cohort had no comorbidities and had hormone receptor-positive, early stage (I/II) cancers. Redlining was associated with poorer survival. When redlining is discretized into four groups with approximate equal-sized intervals, the first and second highest redlining groups are significantly associated with all-cause mortality (HR = 1.226 [1.108, 1.355] for the highest group; HR = 1.159 [1.095, 1.228] for the second highest group). When redlining and its quadratic terms are included in the model, the original and square terms are significantly associated with all-cause mortality (HR = 1.177 [1.111, 1.248] for redlining; HR = 0.982 [0.973, 0.991] for squared redlining). Conclusions: The study suggests that redlining could negatively contribute to breast cancer survival. Persistent place-based mortgage discrimination, as a manifestation of institutional racism, could have long-term effects on people’s health, possibly by impacting health care access or exposing residents to harmful neighborhood conditions. Housing policies that seek to reduce or eliminate place-based mortgage discrimination could contribute to reducing breast cancer survival disparities.
Cardiac events and breast cancer survival analysis in caucasians and minorities: A retrospective study in central Illinois.
Authors: Cheema Asad , Maini Ruby , Koester Cameron , Tandan Nitin , Lara Garcia Odalys Estefania , Regmi Manjari Rani , Parajuli Priyanka , Niaz Zurain , Abedrabo Sabree , Sahib Hamsa , Mirihagalle Noupama , Johnson Alexander , Ibrahim Abdisamad M. , Bhandari Bishal , Delfino Kristin , Robinson Kathy , Desai Meghna R. , Kulkarni Abhishek 
Published: May 2020

e13622 Background: Breast cancer is the most prevalent malignancy affecting the female population in the United States and poses a significant mortality risk. In central Illinois, our objective was to analyze cardiac events (described as a new diagnosis of heart failure, heart failure hospitalizations, and acute coronary syndrome) in patients diagnosed with breast cancer and overall survival. Methods: A retrospective analysis completed in February 2020 identified patients (n = 1618) based on ICD diagnosis codes with a primary diagnosis of breast cancer. The inclusion criteria comprised of confirmed pathology report with diagnosis of breast cancer between January 2014 and December 2017. A cohort of 478 patients was identified as having met the inclusion criteria. Baseline characteristics and qualitative information were obtained from retrospective chart review. Continuous variables were described with measures of central tendency (mean, median) and dispersion (range, standard deviation). Categorical variables were summarized as frequencies and percentages. Furthermore, comparison between categorical variables were analyzed using Chi-Square test. Survival curves were estimated using kaplan-meier methodology and analyzed with a log rank test. Qualitative variables were analyzed using chi-square test and reported as hazard ratio using SAS software. All significance was assumed at the p < 0.05 level. Results: Of the 478 patients that were included as part of the analysis, 425 (89.6%) were of caucasian background and 49 (10.34%) were minorities (Asian, African American, and Hispanic). In regards to heart failure, our data demonstrated increased heart failure hospitalizations in minorities (7.89%) compared to caucasians (1.22%) which was a significant association (p = 0.026). In the overall survival among caucasian and minority groups there was no statistically significant difference (hazard ratio 0.939 with a 95% CI between 0.218-4.048), however it showed slight trend suggesting improved survival in the caucasian population. Conclusions: Our data illustrates that minorities with breast cancer experienced a higher incidence of heart failure when compared to the caucasian population. This supports closer observation at cardiac risk factors of such patients and medical optimization in an effort to prevent cardiac complications. While we did not see a significant difference in overall survival, further studies may be warranted in such population.
Healthcare disparities and the demand for expanding hereditary breast cancer screening guidelines in African Americans.
Authors: Ciuro Jordan Alana , Ahsan Samira , Beyer Alisha , Jackson Nancy 
Published: May 2020

e13636 Background: The role of predictive genetic testing on cancer care continues to rise in the healthcare community due to increased development, high demand and utilization of multi-panel testing and genome sequencing. BRCA1 and BRCA2 (BRCA1/2) mutations constitute some of the most common, targetable and clinically important markers in breast cancer. Individuals who harbor BRCA1/2 mutation have a substantially increased risk of developing a multitude of cancers, including breast and ovarian cancer. Early detection of these mutations leads to genetic and prevention counselling. The National Comprehensive Cancer Network (NCCN) guidelines recommend BRCA1/2 screening in high risk individuals however has not incorporated differences within ethnic cohorts. Methods: This study reviewed data collected from a genetics clinic in a tertiary community hospital from 2008 to 2018 to analyze the prevalence of BRCA1/2 mutations in various ethnicities as well as identify high risk personal characteristics and family history. A retrospective chart analysis was conducted on 1090 high risk patients seen for genetic counselling for hereditary breast and ovarian cancer syndrome. Results: Among cases, BRCA1/2 mutations were significantly more common in African American when compared to non-Ashkenazi Jewish Caucasians (8.1% vs 3.6%, p = 0.020). African Americans were more likely to have a personal history of any cancer compared to non-Ashkenazi Jewish Caucasians (90.4% vs 84.5 %, p = 0.048). African Americans were also more likely to have personal history of breast cancer compared to non-Ashkenazi Jewish Caucasians (86.4% vs 79.6%, p = 0.048). Regarding family history, there was no significant difference in the prevalence of cancer. Conclusions: In conclusion, we observed a significantly higher rate of BRCA1/2 in the African American population when compared to non-Ashkenazi Jewish Caucasians. Given the documented social barriers such as insurance and lack of knowledge of family history, the prevalence of BRCA1/2 might be underrepresented in literature. It is critical for healthcare providers to assess probability of BRCA1/2 mutations in the African American population and consequently order genetic testing when appropriate. Future studies are needed in this ethnic cohort to establish if a more tailored approach would help identify higher risk individuals.
The actionable genomic mutational landscape in solid tumours.
Authors: Loddo Marco , Hardisty Keeda-Marie , Thatcher Robert Paul , Haddow Tiffany Eira , Williams Gareth Haydn 
Published: May 2020

e13642 Background: The recent exponential increase in targeted agents and immunotherapies provide new therapeutic opportunities for patients with advanced cancers who have failed first line therapy. However, lack of comprehensive precision oncology testing as part of routine pathology assessment means potential therapeutic opportunities are difficult to identify or remain undiscovered for many patients. Methods: To address this unmet clinical need we established Oncofocus, a clinically validated, ISO15189/2012 and CLIA accredited, precision oncology test optimized for analysis of small diagnostic PWET clinical biopsy samples (sample acceptance 94%). Oncofocus detects actionable genetic variants in 505 genes linked to 764 anti-cancer targeted therapy protocols, either on-market FDA and EMA approved, carrying ESMO and NCCN guideline references or currently in clinical trials. Oncofocus trending data was analyzed for a real-life cohort of 1111 patients with the aim of determining the frequency of actionable mutations in this population. This cohort represent patients with advanced stage disease who underwent Oncofocus testing having failed first line treatment protocols. Results: Analysis of trending data revealed a complex mutational landscape in which 90% of solid tumors harbored actionable mutations. The majority of patients harbored one or more actionable mutations (median 2, range 0-13) affecting key cancer related regulatory networks including the PI3K/AKT/MTOR and RAS/RAF/MEK/MAPK signaling pathways, DNA-damage repair pathways and cell cycle checkpoints. Actionable genetic variants across 33 DNA Damage and Repair (DDR) genes were identified in 30% of tumors. Using a defined predictive cut point of > 10% for tumor proportion score, PD-L1 expression levels were significantly raised in 19% of cases. Abrogation of DDR function and elevated PD-L1 levels were identified in 5% of patients, a subpopulation potentially more responsive to immunotherapy. Notably, many of the actionable mutations identified did not show linkage with histological type or site of origin. Conclusions: Our data indicates that comprehensive precision oncology testing should be strongly considered as part of the diagnostic work up for all patients with advanced cancers, independent of tumor type, thereby ensuring capture of all targeted therapy opportunities and accelerating “site agnostic” molecular basket clinical trials. Comprehensive precision oncology testing was performed successfully on routine biopsy samples circumventing the requirement for fresh tissue or large sample specimens.
Validation of the fully automated idylla system for microsatellite instability detection in Chinese colorectal cancer patients.
Authors: Wang Qian , Zhang Jing , Yu Chengli , Bao Longlong , Cai Xu , Jiang Wenhua , Huang Dan , Zhu Xiaoli , Bai Qianming , Zhou Xiaoyan 
Published: May 2020

e13644 Background: Mismatch repair (MMR)/microsatellite instability (MSI) testing is recommended by NCCN Guidelines to screen for Lynch Syndrome as well as to predict response to immune checkpoint inhibitors in solid tumors. Conventional methods for MSI detection, immunohistochemistry (IHC) and polymerase chain reaction (PCR), often require non-tumor controls as well as a long turnaround time. The Idylla system, in contrast, is a fully automated quantitative PCR unit with a turnaround time of 2.5 hours. Neither does it require normal tissue or special training to operate. The Idylla MSI Test has been CE-marked for its reliability among Caucasian colorectal cancer (CRC) patients, but has never been validated in Chinese CRC population. Methods: Formalin-fixed paraffin-embedded (FFPE) tissue samples were collected from 87 CRC patients and were subjected to MMR/MSI detection using IHC, PCR and the Idylla test separately. The Idylla MSI Test incorporates 7 novel MSI loci, ACVR2A, BTBD7, DIDO1, MRE11, RYR3, SEC31A, and SULF2. The sensitivity and specificity of the Idylla system were evaluated in comparison with PCR and IHC. Results: Of the 87 patients enrolled, both IHC and PCR identified 55 to be MMR-deficient (dMMR)/MSI-high (MSI-H), of which 4 were MSS using Idylla, and 32 to be MMR-proficient (pMMR)/microsatellite stable (MSS) where Idylla classified one as MSI-H, yielding a sensitivity of 92.7%, a specificity of 96.9% and an overall concordance of 94.3%. Re-examination of the 5 discordant cases (4 false negatives and 1 false positive) using DNA extractions instead of tissue slices on the Idylla platform displayed 100% consistency with IHC/PCR. Confirmation on the Idylla system using recut sections corrected 3 false negatives and 1 false positive, with all tumor contents of ≥20%, 1 Idylla-defined MSS sample with 5% tumor content remained discordant even after sample enrichment. Conclusions: The Idylla system provides a fast, reliable, and user-friendly solution to MSI detection in Chinese CRC patients with high sensitivity and specificity. Upfront assessment of tissue sample quality ( i.e. tumor area and tumor cell fraction) is critical for the accuracy of this test. The reproducibility of the assay warrants further investigation.
Determine the impact of hybrid capture-based comprehensive genomic profiling (CGP) on the treatment strategies in patients with solid tumors: A national, multicenter, retrospective study.
Authors: Disel Umut , Kose Fatih , Bilici Ahmet , Özgüroğlu Mustafa , Saglam Sezer , Seker Mesut , Aksoy Sercan , Tek Ibrahim , Eralp Yesim , Mandel Nil Molinas , Demir Gokhan , Arslan Cagatay , Demiray Mutlu , Salepci Taflan , Ozturk Mehmet Akif , Selcukbiricik Fatih , Temizas Gokce , Fidan Ebru Gul 
Published: May 2020

e13646 Background: Most of the frequent cancers present a large number of very rare targetable genomic alterations. Moreover, some oncogenic drivers are shared across several diseases, and their targeting could improve outcome. We think that testing a large number of genes across all tumor types could improve outcomes in patients with “hard-to-treat” advanced cancers. The most important factor for the cancer patient to benefit from precision medicine therapy is the detection of the targeted driver mutations. The objective of this study is to determine clinical advantages of hybrid capture based comprehensive genomic profiling over classical diagnostic methods in the treatment strategies of patients with advanced stage diverse solid tumors in Turkey. Methods: This study was designed as a national, multicenter, descriptive, non-drug, retrospective cohort study. Study data were collected from medical files of patients. Besides, a survey was conducted to investigate the impact of CGP results on the treatment decisions of the clinicians. Results: The study included the data of 118 patients (55; %46.6 female, 63; %53.4 male). The mean period between the diagnosis and CGP analysis was 748 days. For either due to progression (97; 75.2%) or intolerance to therapy (12; 9.3%), the treatment of some cases was discontinued after CGP analysis. The results of the electronic survey for the clinicians indicated that the 57;48.3% of the clinicians change their treatment approach based on the results of the CGP analysis, of these 24; 42.1% preferred on-label treatments,3; 5.3% clinical trials and the 30; 52.6% preferred off-label treatments. 59;69.8% of the clinicians declared that their patients can reach to the revised treatment. 48;42.1% of the clinicians expressed that CGP support was very important in the last treatment decision. This is the interim descriptive statistics of the study. Conclusions: This is the preliminary results of the study. Conclusions will be done after the final analysis of the study
Economic burden of not testing for FLT3 to treat acute myeloid leukemia.
Authors: Henderson Raymond , Smart Dave , French Declan , Clark Jordan , Bloom Kenneth Joel , Hosty Derek , Lawler Mark 
Published: May 2020

e13652 Background: Acute myeloid leukemia (AML) is a hematologic neoplasm with poor 5-year survival (33%; US 2016), a median survival of only 4 months for relapsed/refractory cases, and in 2016, a US incidence of 19,950 cases and 10,340 deaths. With the largest patient cohort over 65, AML treatment costs in the first year are > $25,000 per patient per month (PPPM); the initial month’s cost is $82,328. Mutations in the FMS-like tyrosine kinase 3 ( FLT3+) pathway confer resistance to standard chemotherapy and reduce the likelihood of survival after relapse. In 2017 and 2018, the FDA approved midostaurin and gilteritinib, two current FLT3+ precision medicines for AML. Here, we determine the economic burden of not testing for FLT3+. Methods: AML healthcare costs were assessed and modelled for the following settings: hospital, outpatient, emergency, and primary care. Pharmaceutical activity and cost data were extracted from the Centers for Medicare and Medicaid Services (CMS) database, employing Diaceutics’ proprietary Global Diagnostic Index. Our model forecasts the economic impact of precision testing to guide FLT3+ precision medicines in 2017 through 2019. Our algorithm calculates the number of AML patients with FLT3+ based on AML Medicare patients in the Healthcare Cost and Utilization Project database and FLT3+ prevalence and switching data. Results: Total US 2016 AML costs were $1.574 billion (bn), consisting of (i) hospital care $1 bn (including $229 million (mn) for bone marrow transplantation and $20.5 mn for pharmaceuticals); (ii) outpatient care $9.8 mn; (iii) emergency care $553.9 mn; (iv) primary care $6.6 mn. Analysis of CMS data revealed a paucity of FLT3+ testing to guide therapy. We estimate that after testing, 2,164 FLT3+ Medicare patients could benefit from precision medicine interventions, generating 2,965 quality-adjusted life years (QALYs) or 2,783 QALYs when administering midostaurin or gilteritinib respectively. Conclusions: This study is the most detailed analysis of the economic burden of AML among US Medicare patients to date and is the only AML cost-of-illness study to incorporate data concerning patients’ QALYs lost by failure to employ precision medicine. This study not only illustrates the minimal FLT3 testing conducted, but also the lack of precision medicines administered.