bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mammography adherence among medically underserved women undergoing cancer genetic risk assessment.
Authors: Schwartz Candice , Chukwudozie Ifeanyi Beverly , Tejeda Silvia , Vijayasiri Ganga , Abraham Ivy , Remo Mylene Hernandez , Shah Hiral A. , Ferrans Carol Estwing , Warnecke Richard , Hoskins Kent 
Published: May 2020

1554 Background: Medically underserved women bear a disproportionate burden of breast cancer (BC) mortality. Early detection is vital for reducing BC deaths. Cancer genetic risk assessment (CGRA) provides an opportunity to identify women at highest risk so that risk-adapted screening can be implemented. The effect of CGRA on mammography adherence among underserved women is unknown. Methods: We conducted a study to test the feasibility of performing cancer genetic risk assessment (CGRA) as part of standard primary healthcare at two Federally Qualified Health Centers in Chicago, IL. Racial/ethnically diverse women age 25-69 without a personal history of BC underwent CGRA at the time of an annual well-visit and received the result from their PCP. Medical record review provided data on mammography adherence. Demographic data and measures of perceived BC risk, BC cultural beliefs, fatalism, and BC worry were collected with an enrollment survey. McNemar’s test compared the rate of adherence to screening mammography before and after implementation of CGRA, defined as completing a screening mammogram within 18 months prior to or following CGRA, resp., among women eligible for screening (age > 40 at study enrollment). Logistic regression models tested for associations between mammography adherence and demographic characteristics/health beliefs. Results: Data was available for 90 participants with increased BC risk (IR) who were eligible for screening and 98 eligible, average risk (AR) participants (in total, 61% black and 37% Latina). Overall, adherence improved from 38% at baseline to 49% following CGRA (p = 0.03). Adherence increased from 35% to 51% among IR participants (p = 0.04), and from 40% to 47% among AR participants (p = 0.39). Data on predictors of adherence will be presented. Conclusions: Implementing CGRA as a standard component of primary healthcare improved adherence to screening mammography among racial/ethnically diverse underserved women. The effect was seen primarily in those with increased risk. This intervention could be used to improve uptake of mammography in the subgroup of underserved women who benefit the most from screening.
Evaluation of a mobile cervical cancer screening program in São Luis, Maranhão, Brazil: Impact and challenges.
Authors: Cossetti Leal Rachel Jorge Dino , Pereira Emanuel Cabral , Ribeiro Thamires Sales , Machado Monalisa Leal Matta , de Carvalho Roseline Braga , Neme Larisa Machado , Alves Deborah Costa , Leal Plinio da Cunha , Brito Luciane Maria Oliveira , Chein Maria Bethânia da Costa 
Published: May 2020

1558 Background: Cervical cancer (CC) still represents a public health priority in Brazil, with estimated incidence of 15,43 cases per 100.000 women. CC is the most frequent cause of cancer and cancer-related mortality in women in the state of Maranhão. The Brazilian national screening program recommends cervical cytology (Pap test) every 3 years in women 25-64 years old. Although of public access, the screening program continues to be non-organized. This was a real-life CC screening intervention through a mobile screening unit (MSU) in communities of São Luis, Maranhão. Methods: Prospective, intervention-based, analytic study, from April to August, 2018. Women in the assisted communities were offered Pap tests. Tests were collected and results were retrieved within 4 weeks along with further screening recommendations. Quality control and monitoring of the test were done. A structured questionnaire was applied. Results: 960 tests were collected and 545 women answered the questionnaire. Median age: 43 (34 – 52), with 88.2% of women within the target age. Socioeconomic charachteristics: 47.3% completed high school education; 37.8% were housewives, 16.1% were unemployed; 56.3% were married; 59.8% had a monthly family-income up to 1 minimum wage ($ 250,00). Previous Pap tests and difficulties: 94.1% had at least one previous test; 78,2% had a test within the past 3 years; 48.4% referred to dificculties to scheduling, 23.3% time constraints, 11.2% being ashamed, and 10.4% financial restrains. There were 65 (6.9%) abnormal results (LSIL in 3%, HSIL in 0.7%, and in situ adenocarcinoma in 1 case), for whom further investigation was recommended. Follow-up was possible in 31 of these cases. More than 50% were still awaiting for additional screening tests at time of contact (>6 month interval). Conclusions: MSU strategy faccilitated the access to Pap tests, their results and recommendations. Although Pap test was easily available, the non-organized process of invitation, follow-up and referal of positive cases for further investigation, as offered by the Brazilian public health services, limit screening efficacy and CC control.
Epigenetic control of breast cancer susceptibility.
Authors: Marino Natascia , German Rana , Harikrishna Nakshatri , Podicheti Ram , Vode Ashley , Liu Jun , Huang Jie , Rusch Douglas B , Cao Sha , Storniolo Anna Maria 
Published: May 2020

1560 Background: Epigenetic mechanisms such as DNA methylation are important regulators of gene expression and are frequently dysregulated early in breast carcinogenesis. The relationship between DNA methylation aberrations in normal breast tissue and breast cancer risk remains unclear. Methods: Disease-free breast tissue cores donated by 71 high-risk (Tyrer-Cuzick lifetime risk ≥20%) and 79 average-risk women were obtained from the Komen Tissue Bank and processed for whole methylome (Diagenode's MethylCap Library and single-end 75-bp sequencing on Illumina Nextseq) and whole transcriptome (Illumina Nextseq) profiling. Reads from RNA-seq data were aligned to the human genome reference, GRCh38.p12 using STAR v.2.5.2b and tested for differential gene expression using DESeq2 ver. 1.24.0. For DNA methylation data, difference of variation in deduplicated read coverage among 250-bp fixed sized bins spanning CpG islands between high- and average-risk libraries was computed as z-ratios to identify differentially methylated regions. Pathway analysis was performed using IPA v06_01. Results: We identified 1355 CpGs that were differentially methylated between high- and average-risk breast tissues (ΔZ > 0.5, FDR < 0.05). Hypomethylated CpGs were overrepresented in high-risk tissue and were found predominantly (68%) in non-coding regions. Hypermethylated CpG sites were found equally in the gene body and non-coding regions. Transcriptomic analysis identified 112 differentially expressed genes (fold change≥2, FDR < 0.05), involved in chemokines signaling, metabolism and estrogen biosynthesis. Among those, FAM83A (logfc = 2.3, FDR = 0.004) was previously described as epigenetically dysregulated in multiple cancers and transforms breast epithelial cell in vitro. Methylation-expression correlations revealed 11 epigenetically regulated genes including cellular transformation-associated BMPR1B. Two hypomethylated/upregulated long non-coding RNAs were also identified in high-risk breasts. Conclusions: This is the first gene expression/DNA methylation analysis of normal breasts from women at either high or average risk of breast cancer. Our discovery of epigenetically regulated genes associated with breast cancer risk provides an opportunity to mechanistically dissect breast cancer susceptibility and risk-associated molecular alterations. Unlike the current focus of identifying germline mutations or single nucleotide polymorphisms responsible for higher risk, our studies reveal an epigenetic mechanism, which is not discernable through simple genomic sequencing.
Mammography utilization among women with a negative circulating tumor DNA-based early cancer detection test.
Authors: Jones Claire , Parker Alex , Warren Andrew , Vanenkevort Erin A , Gupta Mudit , Lagerman Braxton , Honushefsky Ashley M , Cohain Ariella , Leeming Rosemary , O'Broin-Lennon Anne Marie , Buchanan Adam H 
Published: May 2020

1563 Background: Blood-based tests may enable minimally invasive detection of multiple cancer types. One such test, CancerSEEK, employs ctDNA and protein biomarkers for this purpose. Test performance has been evaluated in women without a history of cancer in an ongoing prospective study called DETECT-A. The introduction of such blood tests holds promise, and their future utility lies in augmenting, not displacing, standard-of-care (SOC) cancer screening. One important safety concern is that a negative test result could provide false reassurance that discourages adherence to SOC cancer screening. To investigate this possibility, we studied delivery of mammography to DETECT-A participants before and after receipt of a negative CancerSEEK result. Methods: DETECT-A screened 10,000 women aged 65-75 using CancerSEEK. Participants completed a survey about cancer screening at enrollment and at one-year post-enrollment. We analyzed only those participants who had received a negative CancerSEEK result, were insured by Geisinger Health Plan (GHP), and had completed both surveys. GHP claims data were used to identify mammograms performed within one year prior-to and post-enrollment. Overall utilization was determined by combining claims and survey data at enrollment and one-year post-enrollment. In addition to comparing SOC screening rates pre- versus post-testing, we evaluated the impact of primary care physician (PCP) type (Geisinger versus any other institution), as screening reminder mechanisms differ between institutions. Results: Of the 2,241 participants who met analysis criteria, 73.6% (n = 1,650) had a mammogram in the year before enrollment while a significantly great number (79.3%, n = 1,777) did so during the one-year follow-up (χ2(1) = 59.05, p < 0.001). At enrollment, there were 591 participants who had not had a mammogram completed in the previous year, but 404 (68.4%) of them did have a mammogram during the one-year follow-up. The rate of change in mammography utilization did not differ between those who had a Geisinger versus a non-Geisinger PCP (χ2(2) = 1.83, p = 0.40). Conclusions: Participants in a study using a novel blood test for earlier cancer detection had a significantly higher rate of annual mammography after study enrollment and testing. These results indicate that introduction of a minimally invasive ctDNA and protein biomarker-based cancer screening test may engender greater, not lesser, utilization of SOC cancer screening. Further study is required to understand the root causes of increased utilization in this context.
Protein intake and breast cancer incidence and mortality.
Authors: Pan Kathy , Larson Joseph C , Chlebowski Rowan T. , Mortimer Joanne E. , Manson JoAnn E , Van Horn Linda , Rohan Thomas E , Lane Dorothy 
Published: May 2020

1569 Background: Associations between dietary protein intake and breast cancer are unclear, in part due to limitations of dietary self-report. Women’s Health Initiative (WHI) investigators compared the accuracy of food frequency questionnaire (FFQ) data on energy and protein intake with objective measures of dietary intake using biomarkers (doubly labeled water for energy and urinary nitrogen for protein [n=544]). Subsequently, regression equations incorporating participant characteristics were developed acknowledging differential reporting dietary data errors based on participant characteristics (Neuhouser Am J Epidemiol). FFQ findings were then used to determine biomarker- adjusted animal vs vegetable protein ratios. Methods: We examined associations of energy and protein intake with breast cancer incidence and mortality in Women’s Health Initiative (WHI) participants 50-79 years of age at entry between1993-1998, with breast cancers verified by medical record review and survival enhanced by serial National Death Index (NDI) searches through 2016. Associations between sources of protein intake (animal versus vegetable) quintiles and breast cancer incidence and mortality were estimated using multivariable Cox proportional hazards regression. Results: With 100,024 eligible participants, after 14 years follow-up, women with higher total protein intake had greater body mass index, were more likely White, menopausal hormone therapy users with higher total energy intake and fat intake. With 6,340 incident breast cancers, 764 deaths from breast cancer and 2,059 deaths after breast cancer, higher vegetable protein intake was associated with significantly lower breast cancer incidence (P for linear trend = 0.01) while higher animal protein intake was associated with significantly higher breast cancer incidence (P for linear trend = 0.03). Higher vegetable protein intake was also associated with significantly lower risk of death after breast cancer (P <0.001) but not with lower risk of deaths from breast cancer (breast cancer followed by death attributed to breast cancer). Animal protein intake was not associated with deaths from breast cancer or deaths after breast cancer. Conclusions: Based on findings from biomarker-calibrated determination of protein intake by source, higher vegetable protein intake was associated with significantly lower risk of breast cancer incidence and of death after breast cancer while higher animal protein intake was associated with significantly higher risk of breast cancer incidence, but not mortality.
The increasing incidence of colorectal cancer in younger patients in the United States: Who, what, when, and where?
Authors: Abel Mary Kathryn , Liao Cheng-I , Van Loon Katherine , Tian Chunqiao , Darcy Kathleen M. , Mann Amandeep Kaur , Kapp Daniel Stuart , Chan John K. 
Published: May 2020

1573 Background: Prior studies have shown an increase in the rate of colorectal cancer (CRC) in young individuals in the United States. However, few studies have evaluated the health disparities that exist in this population, particularly using large, national cohorts. We examined differences in age, race, stage, region, and tumor location in younger and older patients with CRC. Methods: Data were extracted from the United States Cancer Statistics (USCS) for individuals diagnosed between 2001 and 2014. CRC incidence data among individuals < 50 years old were compared to those > 50 years old. Age-specific and age-adjusted incidences and trend analyses reported as annual percent change (APC) were performed using SEER*Stat and Joinpoint regression. Results: Of 1,886,441 individuals, the overall age-adjusted incidence of CRC decreased from 52.59 (per 100,000) in 2001 to 35.22 in 2014, with an APC of -3.24. Although over 35% cases were diagnosed in the Southern United States, the Northeast had the highest age-adjusted incidence at 45.26 per 100,000 patients. Younger patients were diagnosed with distant disease at 25.8% compared to only 18.4% in older patients. Younger patients were also more likely to have sigmoid or rectal cancers compared to older patients (64.3% vs. 45.7%). Of the 170,244 individuals < 50 years, 90,855 (53.4%) were men and 79,389 (46.6%) were women. The age-specific incidence in this younger cohort increased from 5.63 to 6.48 between 2001-2014, with an APC of +1.24 in 2001-2008 compared to +2.55 in 2012-2014. The incidence of CRC in patients aged 0-29, 30-39, and 40-49 years was 0.41 (per 100,000), 6.08, and 21.09, respectively. Black individuals < 50 years had the highest age-specific incidence of CRC (7.16 per 100,000) compared to Asian (6.43), White (6.07), or Hispanic (4.76) individuals. Conclusions: Our data suggests that CRC is increasing in young patients, particularly for those between 40-49 years and Black individuals. In our younger cohort, CRC was more commonly found in the sigmoid colon and rectum compared to older patients. Further research is warranted to direct resources towards improved colonoscopy or sigmoidoscopy screening for younger patients at risk.
Hereditary leiomyomatosis and renal cell cancer syndrome (HLRCC): Genotype and phenotype characteristics in a cohort of 197 patients.
Authors: Sanchez-Heras Ana Beatriz , Castillejo Adela , García-Diaz Juan de Dios , Robledo Mercedes , Teule Alex , Sánchez Rosario , Zuñiga Angel , Lastra Enrique , Duran Dominguez Mercedes , Llort Gemma , Yague Carmen , Ramon Y Cajal Teresa , Lopez Consol , Lopez Adria , Balmana Gelpi Judith , Robles Luis , Fonfria Esparza María , Chirivella Isabel , Gomez Luis , Soto José Luís 
Published: May 2020

1580 Background: HLRCC is a hereditary condition with autosomal dominant inheritance due to germline mutations in the fumarate-hydratase gene ( FH). It is characterized by skin leiomyomas (SLM) in 48-84% of individuals, uterine leiomyomas (ULM) in 30-72%, renal cysts (RCy) and renal cell cancer (RCC) in 15-34%. We aimed to describe the genetics, the clinical features and the potential genotype-phenotype associations in the largest cohort of FH mutation carriers from Spain. Methods: We performed a multicenter, observational, retrospective study of individuals with genetic or clinical diagnosis of HLRCC. We collected clinical information from medical records. We analyzed genetic variants and looked for genotype-phenotype associations. Statistical analyses were performed by IBM-SPSS Statistics-v.22. Results: We included 197 individuals (113 women, 84 men), 74 index cases and 123 relatives. Twenty-seven different variants were detected, 26 pathogenic (12 missense, 5 frameshift, 4 large-deletions, 3 splice-site and 2 nonsense) and 1 variant of unknown significance (missense). Of 182 patients with full skin examination, 64.8% presented SLM (median age 36 years; range 8-85). ULM were diagnosed in 90.3% of 103 women with gynecologic exam (median age 30 years; range 17- 55). Hysterectomy was performed in 62.9% (median age 34 years; range 21-54). Of 153 patients with radiological records, 37.3 % presented RCy. Nineteen patients (10.9%) presented RCC, 11 males and 8 females (median age 37 years; range 10-67). The histological diagnoses were: 14 papillary, of which 10 were type 2; 3 clear cell carcinoma and 2 unclassified carcinoma. Six tumors had stage I, 2 stage II, 3 stage III, 4 stage IV, and 4 not available. The median overall survival among patients at stages 3-4 was 2.9 years [1.3-4.5]. Patients with missense pathogenic variants showed higher risk of developing SLM (p = 0.043) and ULM (p = 0.002) than those with loss of function variants. Conclusions: In our cohort, the frequency of RCC (10.9%) is lower than that published in cohorts of similar sample size. The most frequent histology was the papillary type-2; however, other histological patterns do not exclude HLRCC. Individuals with missense pathogenic variants show higher incidence of SLM and ULM.
Value of multigene panel retesting of families with BRCA1/2 mutation-negative hereditary breast and ovarian cancer (HBOC).
Authors: Meshoulam Nikolaeva Ekaterina , Terés Raul , Camacho Daniela , Bujosa Aida , Borrell Maria , Gallardo Pablo , Martin Berta , Calvo Nuria , Lopez Consol , Alfonso Rosa , Sola Carla , Cornet Monia , Cliville Nuria , Lasa Adriana , Tibau Ariadna , Arqueros Cristina , Barnadas Agusti , Ramon y Cajal Teresa 
Published: May 2020

1582 Background: Despite the use of clinical eligibility criteria and mutation predictive models, a great proportion of families are negative for germline mutations in BRCA1/2 genes. Traditionally, risk assessment of inconclusive results included the recommendation of high-risk surveillance protocol, the update of incident cancer cases in the family and the consideration of additional testing to rule out the possibility of phenocopy. More recently, next generation sequencing multigene panels have become a standard practice in cancer genetics clinics worldwide. We addressed the value of multigene panel retesting of BRCA1/2 negative HBOC families in our institution. Methods: After genetic counseling session and informed consent, a total of 137 individuals (119 probands and 18 extra cancer-affected relatives) from distinct BRCA1/2 negative families were retested using a panel containing 11 breast and ovarian cancer susceptibility genes ( BRCA1/2, PALB2, ATM, CHEK2, PTEN, TP53, STK11, BRIP1, RAD51C, RAD51D). Results: According to the BOADICEA model, the remaining probability of mutation in BRCA1/2 or PALB2 genes in our cohort was 5.5% (0.1-61). The reasons for considering retesting were the addition of any incident cancer diagnosis in 33 cases (24%), a prior study with a low sensitivity screening technique (dHPLC) in 6 families (5%) and the expansion of the study to other putative breast and ovarian susceptibility genes in 98 families (71%). Overall, 3 pathogenic (2 BRCA2, 1 CHEK2) and 8 likely pathogenic variants (1 BRCA2, 4 CHEK2 and 3 ATM) were found. The prevalence was 8%. The detection rate among 19 families with a > 10% remaining probability of mutation in BRCA1/2 and PALB2 genes was 26%. The 3 clinically significant variants in BRCA2 were detected in 2 families and 1 updated cancer family history (BOADICEA remaining probability of 59, 61 and 12%, respectively). Cascade testing was subsequently done in 15 relatives resulting 8 in mutation carriers and 9 true negatives. Conclusions: Our results support the value of updating cancer incident cases and considering expanded panels in selected families.
Chemotherapy remote care monitoring program (CRCMP): Integration of an SMS text patient-reported outcome (PRO) in the electronic health record (EHR) to identify patients needing pharmacist intervention for chemotherapy-induced nausea and vomiting (CINV).
Authors: Hough Shannon , McDevitt Rachel , Nachar Victoria , Kraft Shawna , Brown Anna , Christen Catherine , Walters Barbara , Smerage Jeffrey B. 
Published: May 2020

2001 Background: CINV is a feared side effect of cancer therapy. Despite advances in management, CINV is a common cause for emergency department (ED) evaluation and other unplanned health care utilization. The University of Michigan Rogel Cancer Center initiated the CRCMP to proactively identify patients (pts) experiencing CINV and intervene prior to the need for urgent evaluation. Methods: Pts receiving highly emetogenic chemotherapy are identified by administration of a NK1 antagonist. Once enrolled in the CRCMP, pts receive a daily text message survey for 7 days after treatment. The survey is based on the validated MASCC anti-emesis tool (MAT). Responses are stored within a flowsheet in the EHR. Responses above a set threshold trigger a message to the team pharmacist for intervention. Data presented was reviewed from EHR and claims data. Results: In 8 mo, 652 pts received a NK-1 antagonist (2244 total cycles) and 387 pts enrolled in the CRCMP (59%). Each pt enrolled for an average of 1.8 cycles of chemo (range 1-8). Of patients enrolled, 61.4% were female and 86.2% were Caucasian. Chemotherapy intent was curative for 51.7% and palliative for 48.3% of pts. Pts enrolled most commonly received cisplatin-based (29.7%) followed by carboplatin-based (22.5%), and 5-fluoruracil-based (20.9%) therapy. Text message response rate was 94% (N=18,143 responses of 19,256 total messages sent). During 861 cycles of therapy, 7% of responses noted vomiting and 33% of responses noted nausea. Since implementation of CRCMP, total hospitalization, ED, and urgent care use has decreased (p=0.029) compared to historical data. When utilization for nausea-related diagnoses was considered, the reduction was more notable (Table). Conclusions: Pts engaged in the CRCMP for CINV, allowing for rapid assessment of PROs by a pharmacist. Health care utilization related to nausea was reduced following implementation of CRCMP. While these changes were numerically small, reduction in unnecessary care utilizing PROs can contribute to high value care for cancer patients. [Table: see text]