bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of 5- and 10-year breast cancer risk predictions.
Authors: Hopper John L. , Dite Gillian S. , Spaeth Tuff Erika Leigh 
Published: June 2023

10529 Background: Breast cancer risk assessment is valuable in personalizing risk-reduction and screening approaches for the general population. Maximizing the benefits while reducing the harms associated with current breast cancer screening and risk-reduction recommendations should increase the efficacy of these paradigms. Because healthcare providers have limited time with their patients, we developed a risk prediction model, BRISK, which uses the most important clinical risk factors for breast cancer (in an easily collected format), polygenic risk and mammographic density. We previously validated BRISK 5-year risk predictions and found that it performed better than IBISv7 and BCRAT. Methods: The dataset comprised 241,633 women (mean age at baseline assessment = 56.6 years). We included all races/ethnicities available in the UK Biobank. There were 3726 women affected during the first five years of follow-up and 7482 women affected during the full 10 years of follow-up. We compared the performance of the 5-year and 10-year risk predictions by assessing the association with breast cancer using Cox regression to estimate the hazard ratio (HR) per SD of risk, discrimination using calculating Harrell’s C-index and calibration using logistic regression to estimate the slope and the intercept of the logit of the risk predictions. Nelson–Aalen estimates of the hazard function by quintiles of risk and standardized incidence ratios (SIRs) of the number of breast cancer cases expected were used to illustrate performance. Results: The predictive performance of BRISK was consistent for 5-year and 10-year risk predictions. Discrimination was similar, with a Harrell’s C-index of 0.645 (95% CI = 0.636, 0.654) for the 5-year risk and of 0.638 (95% CI = 0.632, 0.645) for the 10-year risk. We used Nelson_Aalen cumulative hazard estimates to compare breast cancer incidence by risk quintile for both 5 and 10-year risk. Both risk scores overestimated risk in the top two deciles with the 5-year expected risks of 2.8% and 5.0% corresponding to observed risks of 2.3% and 3.3%. The 10-year expected risks for the top two deciles were 5.6% and 9.8% while the corresponding observed risks were 4.6% and 6.4%. Finally, we used clinically actionable thresholds to show the standard incidence ratios (SIR) of 1.77 (95% CI = 1.69, 1.85) for women ≥3% 5-year risk and 2.05 (95% CI = 1.93, 2.18) ≥8% 10-year risk. Conclusions: The BRISK 5-year and 10-year risk prediction perform equally well. There is an overestimation of risk for the top decile in both models. This is important to consider in risk-management conversations between clinician and patient. While the observed risk of the top decile remained above the 3% 5-year risk threshold used in the United States, the top decile observed risk dropped below the 8% 10-year risk threshold used in the United Kingdom. Risk scores are not used in isolation, but it may be preferable to err on the side of overestimation rather than underestimation.
Epidemiologic effectors on the breast tumor microenvironment: Results from the Cancer Prevention Study-II and -3 cohorts.
Authors: Elsebaie Maha AT , Amgad Mohamed , Hodge James M. , Gaudet Mia M. , Teras Lauren R. , Shah Ami N. , Cooper Lee A.D. 
Published: June 2023

10530 Background: Despite breast cancer being the leading cancer among women, we have a poor understanding of the impact of epidemiologic risk factors on its tumor microenvironment (TME). We examined risk factors for TME favorability using a novel aggregate marker: the Histomic Prognostic Score (HiPS). Methods: Data were from whole slide image (WSI) scans of hematoxylin & eosin slides from women in the Cancer Prevention Studies CPS-II and -3, diagnosed with nonmetastatic breast cancer. Diagnoses occurred between enrollment and the last administrative date (1992/1993 to 2011 in CPS-II and 2006–2013 to 2018 in CPS-3). Median year of diagnosis was 2004 in CPS-II and 2014 in CPS-3. Using the WSI, a deep-learning model was trained to extract features and summarize the morphology of the epithelium, stroma, and tumor-infiltrating lymphocytes within the TME. These features, along with demographic, tumor biomarkers, and survival data, were then used to generate the HiPS, a novel measurement of “ prognostic favorability” of TME, ranging from 0 (favorable) to 10 (unfavorable). Multivariable linear models estimated associations between the HiPS score and epidemiologic risk factors: hormone replacement therapy use (HRT; current vs. former/never), cigarette smoking (current vs. former/never), alcohol intake (>1 drink vs. <1 drink/day), aspirin intake (daily vs. not daily) controlled for, age at diagnosis, body mass index (BMI), race, and cancer detection method (screen- vs. self-detected). Results: We included 1264 CPS-II and 651 CPS-3 participants in the analysis. Compared to CPS-II, CPS-3 participants were younger (mean (± sd) age 54.7 ± 7.6 vs. 72.2 ± 7, p<0.001), heavier (mean (± sd) BMI 27.1 ± 5.8 vs. 26 ± 4.8, p<0.001), and more diverse (7.4% vs. 2.1% non-White, p<0.001). Most breast cancers (69.9% of CPS-II and 64.1% of CPS-3) were screen-detected, p=0.206. Increasing age and BMI were associated with higher HiPS score in both cohorts, Table. Daily aspirin use and current HRT use were associated with lower HiPS scores in CPS-3 only. The inverse association for HRT use was lost in the following subgroups age < 50, ER-, HER2+, TNM stage-1, and screen-detected cancers. Conclusions: Increasing age and BMI have independent adverse effects on breast TME. Daily aspirin intake and current HRT use were only associated with a favorable TME in the younger, more contemporary cohort. Additional studies are needed to confirm these findings and better understand the role of these epidemiologic factors on the TME. [Table: see text]
Trends in mortality caused by neoplasms of the heart in the United States between 2000 and 2019: An observational analysis of disparities by gender and race.
Authors: Shahapurkar Abhishek , Alhariri Housam , Jani Chinmay , Ganatra Sarju 
Published: June 2023

10532 Background: Neoplasms of the heart, primary and metastatic, are relatively rare diseases in the US. Metastatic neoplasms are 30 times more common than primary neoplasms and constitute more than 99.3% of the total neoplasms of the heart. Only a few studies have evaluated the mortality trends of this rare disease. Therefore, we aim to analyze the trends of mortality caused by benign and malignant neoplasms of the heart from 2000-2019 and compare them based on gender and race. Methods: We utilized the CDC WONDER database to extract data on Heart Benign Neoplasms (ICD 10 D15.1), Heart Malignant Neoplasms (C38.0), and overlapping lesions of Heart, Mediastinum, and pleura (C38.8) mortality in the United States between 2000 to 2019. ICD codes were applied to multiple causes of death. Age-standardized mortality rates (ASMR) per 1,000,000 with a 95% confidence interval were presented for the total population, stratified by gender and race. We assessed the mortality trends using joinpoint trend analysis. Results: From 2000 to 2019, 3493 deaths were reported due to neoplasms of the heart, out of which 1672 (47.86%) were due to benign neoplasms, and 1821 (52.13%) were due to malignant neoplasms. Overall, total deaths and ASMR decreased from 221 to 139 and 0.82 to 0.35, respectively, with an Average Annual Percentage change (AAPC) of -3.5. Out of 3493, the majority were females (2254, 64.5%). On evaluating ASMR based on gender, it decreased from 0.65 to 0.32 (AAPC -2.6) for males and from 0.89 to 0.35 for females (AAPC -3.9). On dividing based on racial subgroups, 2962 deaths were in whites, 413 were in African Americans (AA), and 118 were from other races (Asian, Pacific Islanders, Native Indians). On further comparison between Whites and AA, ASMR was found to be higher in AA throughout the study period. For AA, ASMR decreased from 1.18 to 0.51 (AAPC -4.9), and for Whites, from 0.76 to 0.33 (AAPC -2.5). Conclusions: This study has shown a decline in overall mortality trends across genders and races. This could be attributed to increased cardiac workups for cardiovascular conditions and advances in imaging modalities, cardiac oncology, and therapeutic interventions. Although the mortality trend in females is decreasing, they still have higher mortality rates than males. At the same time, although AA showed a higher rate of reduction in ASMR, they showed an overall higher ASMR throughout the study period. Further studies are needed to assess if increased screening, early detection, and management plans are causing a decrease in overall mortality in neoplasms of the heart. [Table: see text]
Association between excess body mass index trajectory and change in monoclonal protein level in patients diagnosed with monoclonal gammopathy of undetermined significance.
Authors: Liu Lawrence , Grandhi Nikhil , Wang Mei , Thomas Theodore Seth , Kumar Akhil , Sanfilippo Kristen Marie , Colditz Graham A. , Chang Su-Hsin 
Published: June 2023

10538 Background: Obesity is a known risk factor for the development of multiple myeloma (MM) and for progression of its asymptomatic premalignant state, monoclonal gammopathy of undetermined significance (MGUS) to MM. Prior studies have demonstrated that monoclonal protein (M-spike) at MGUS diagnosis as well as high M-spike velocity within a year following MGUS diagnosis predict progression of MGUS to MM, making M-spike a useful, readily available, and less invasive (compared to bone marrow biopsy) marker to assess progression risk. However, no studies have evaluated to what extent exposure to high body mass index (BMI) over time influences M-spike trajectory. Methods: Patients diagnosed with MGUS from 1999-2021 in the Veterans Health Administration were identified. We used a natural language processing-based algorithm to confirm MGUS diagnosis and progression to smoldering MM or MM. MGUS patients without IgM or IgD subtype or Diabetes Mellitus and were black or white were included in the analysis. Other exclusion criteria were progression within 5 years of MGUS diagnosis, patients without M-spike level within a year before or after MGUS diagnosis, and patients without BMI data 3 years or more after MGUS diagnosis. The exposure was the trajectory of excess BMI (defined as BMI > 25 kg/m2), defined by an area under the curve (AUC) of excess BMI during the 5 years following MGUS diagnosis. The outcome was continuous M-spike trajectory post-MGUS diagnosis since a prior study demonstrated that this was a reliable marker for progression risk A multivariable mixed model was used to estimate the association of excess BMI trajectory AUC with M-spike trajectory to control for correlation between M-spike values overtime. The covariates included BMI at MGUS diagnosis, M-spike level ( > = 1.5g/dL) at MGUS diagnosis, age at MGUS diagnosis, sex, race, MGUS heavy chain subtype, and light-chain MGUS. Results: After applying the inclusion and exclusion criteria, the analytic cohort consisted of 6757 MGUS patients. Our multivariable analysis demonstrated a positive association between excess BMI trajectory and increasing M-spike trajectory (β = 0.005, p = 0.007). Conclusions: In patients diagnosed with MGUS, increasing BMI over time following MGUS diagnosis was associated with increasing M-spike level. This further supports the relationship between obesity and weight gain in the pathway of MGUS to MM progression.
County-level food insecurity to predict cancer incidence and mortality in the United States, 2015-2020.
Authors: Chen Krista Y. , Blackford Amanda L. , Hussaini S. M. Qasim 
Published: June 2023

10539 Background: Modifiable dietary patterns incorporating inexpensive, calorie-dense, processed foods and meals low in fiber and other nutrients are associated with development of cancer. Inadequate access to quality nutrition is a crucial but underappreciated social determinant of health and predictor of poor cancer outcomes. We investigated the impact of county-level food insecurity on age-adjusted incidence and mortality rates (AAIR, AAMR) for all cancers. Methods: We linked county-level cancer incidence and mortality rates for 2015-2020 from NCI State Cancer Profiles to food insecurity measures from Feeding America and County Business Patterns. Measures included percentage of individuals experiencing food insecurity (as defined by USDA), percentage on Supplemental Nutrition Assistance Program (SNAP) benefits, average cost per meal, and density of fast-food restaurants. AAIR and AAMRs of all cancers per 100,000 individuals were compared between 1st and 4th quartiles for each measure using robust linear regression models with log transformation and population weights. Results: There was an annual average of 1,728,431 cancer diagnoses with AAIR 449 and 599,666 deaths with AAMR 149. Highest AAIRs were observed in >50y (1351), men (488), non-Hispanic Whites (467), and urban counties (459). This differed from highest AAMR groups including >50y (502), men (178), non-Hispanic Blacks (175), and rural counties (168) suggesting factors of increased disease severity or decreased access to care in the latter. Both AAIRs and AAMRs increased significantly when moving from least to most insecure counties, as defined by overall food insecurity, higher proportion of population on SNAP, higher fast-food density, and lower meal cost. AAMRs and AAIRs for lung cancer and CRC, and for rural residents were most exacerbated by changes in all measures of food insecurity, even when adjusting for screening rates for CRC in low access areas. Conclusions: Our study highlights the most food insecure counties have higher cancer incidence and even greater mortality burden. We recognize food insecurity as a proxy for socioeconomic disadvantage prior to and during cancer treatment. These results encourage prioritization of policies that optimize food assistance programs and clinical practices that incorporate food insecurity-related screenings in care delivery models. [Table: see text]
The role of metabolic perturbations in mediating the effects of ambient air pollution on lung cancer in the cancer prevention studies.
Authors: Liang Donghai , Chow Sabrina S. , Sarnat Jeremy A , Diver Ryan , Deubler Emily L , Tang Ziyin , Pope C. Arden , Jerrett Michael , Turner Michele , Wang Ying 
Published: June 2023

10541 Background: Exposure to ambient air pollution is an established risk factor for lung cancer. Investigation on the underlying mechanisms of air pollution carcinogenicity remains challenging due to the complex composition of air pollution and a lack of sensitive biomarkers to accurately measure exposure and corresponding response. To address the knowledge gaps, we applied high-resolution metabolomics to identify metabolic signatures of exogenous air pollution exposures and endogenous processes involved in lung carcinogenesis. Methods: A total of 683 matched lung cancer and control pairs within the established Cancer Prevention Study-II (CPS-II) Nutrition and CPS-3 cohorts were included in this study. The plasma metabolome was profiled with ultrahigh-performance liquid chromatography-tandem mass spectrometry. Assessment of exposure to six ambient air pollutants, including carbon monoxide (CO), nitrogen dioxide (NO2), particulate matter (PM10), fine particulate matter (PM2.5), sulfur dioxide (SO2), and ozone (O3), was conducted using spatiotemporally-resolved models based on residential address at blood draw and calculated based on yearly average levels. We conducted metabolome-wide association studies with multiple linear regression models to assess associations of ambient air pollution and lung cancer with a meet-in-the-middle approach. Models controlled for potential confounders and covariates including age at blood draw, sex, race, body mass index, alcohol consumption, smoking status, passive smoke exposure, vegetable and fruit intake, and educational level. Metabolites significant at the FDR < 0.2 level in the air pollution model were analyzed in the lung cancer model. High-dimensional mediation analysis was used as a secondary analysis to compare results from the meet-in-the-middle analysis. Results: Among 1,204 metabolic features extracted from the blood samples, seven features were significantly associated with air pollution exposure and lung cancer incidence at the FDR < 0.2 level in the meet-in-the-middle analysis. Six features were significant at the p < 0.01 level through high-dimensional mediation analysis. All confirmed metabolites are enriched within peptide, lipid, and amino acid pathways. Gamma-glutamylglutamine and gamma-glutamylmethionine were statistically significantly associated with CO, NO2, and PM10 exposure and lung cancer incidence in both analyses. Conclusions: This is the largest prospective metabolomics study examining biological perturbations associated with air pollution exposure and lung cancer incidence. Peptide metabolism may play an important role in mediating the association between air pollution and lung cancer. Findings from this study will lay the foundation for future studies to further understand the biological mechanisms underlying the carcinogenicity of air pollution.
Global burden and economic impact of vaccine-preventable cancer mortality.
Authors: Bencina Goran , Oliver Edward , Meiwald Anne , Hughes Robert , Morais Edith , Schillinger Julia A , Weston Georgie 
Published: June 2023

10542 Background: Cancer has a high clinical and economic burden, with ~10 million deaths globally in 2020. In Europe, the total cost of cancer was €199 billion in 2018. Infections are responsible for approximately 13% of cancer cases worldwide. Human papillomavirus (HPV) and hepatitis B (HBV) are among the most important infections associated with cancer for which vaccines are available. However, global vaccination rates for these cancer-causing infections remain low (~12% for HPV; 42% for HBV). Elimination of vaccine-preventable cancers is a public health priority, and the World Health Organization (WHO) has proposed a strategy to eliminate cervical cancer and viral hepatitis by 2030. This analysis aims to estimate the global burden and economic impact due to vaccine-preventable cancer mortality. Methods: The number of deaths and Years of Life Lost (YLL) in 2019 from liver cancer caused by hepatitis B (ICD-10 C22), head and neck cancers (ICD-10 C00-14 and C32), and cancer of the cervix uteri (ICD-10 C53) were sourced from the Institute for Health Metrics Evaluation (IHME) Global Burden of Disease. Deaths and YLL were applied to attributable fractions for each vaccine-preventable cancer based on published data. The Value of YLL (VYLL) was estimated by multiplying the GDP per capita (World Bank; in USD) and YLL for each cancer, in each WHO region. Sensitivity and scenario analyses were performed to test the robustness of results. Results: In 2019, there were 479,750 potentially vaccine-preventable cancer deaths and 14,561,049 YLL (38% in males) across WHO regions (Table). The estimated economic impact due to vaccine-preventable cancer deaths was over $171 billion globally with the Americas and European region accounting for 63% of the total cost ($107 billion). Cervical cancer had the highest mortality burden (52% of total deaths). Globally, 78% of non-cervical HPV-related cancer deaths were in males. Conclusions: In 2019, 1,314 people died per day due to vaccine-preventable cancers leading to substantial YLL and economic impact. The overall burden is likely to be higher since several other HPV-related cancers were not included in this analysis. Improved implementation of HPV and HBV vaccination programs should be prioritized to decrease this burden.[Table: see text]
Impact of social media messages on perceived risk and severity of adverse effects and regret of HPV vaccination: The moderating role of decision-making preference.
Authors: Villegas Jorge , Chen Cheng-Chia (Brian) , Lee Min Jee 
Published: June 2023

10543 Background: The HPV vaccine has proven to be a highly effective and safe public health intervention for reducing the risk of various types of cancer. Despite its efficacy and safety, misinformation and negative opinions about the vaccine on social media can lead to negative emotions such as regret among those who have received it. This study investigated the impact of different content of social media messages on perceived risk and severity of adverse effects and regret of HPV vaccination. Methods: An experiment was designed to expose participants to messages posted on social media that manipulated the number of Vaccine Adverse Effects and the appeal used (narrative vs. statistics). The study measured the effect of the message on decisional regret and also assessed preferred level of involvement with medical decision-making. The online study was implemented among college students enrolled in a Midwestern or a South Texas university. We used structural equation modeling (SEM) to systematically test the relationships between the variables of interest. Results: A total of 721 participants were exposed to the experimental materials and completed the questionnaire. The results of the SEM (with overall good fitness of RMSEA = 0.015, CMIN/df = 1.172) suggest that messages that contained more numeric information (standardized regression weights [Std Reg Wght = 0.161]) and more adverse effects of the HPV vaccine (Std Reg Wght = 0.076) led to a higher perception of the risk of vaccine adverse effects. The severity of adverse effects was significantly associated with the number of side effects in the message (Std Reg Wght = 0.147). This increase in perceived risk (Std Reg Wght = 0.182) and severity of side effects of the vaccine (Std Reg Wght = 0.163) seem to increase decisional regret. However, this relationship was moderated by individuals’ preferences for making their own medical decisions. Individuals with a higher preference to make their own health decisions were less likely to experience decisional regret (Std Reg Wght = -0.238). Conclusions: Messages on social media can exacerbate negative emotions and lead to hesitation in following future medical advice. Encouraging individuals to play a more active role in their medical decision-making appears to reduce this negative emotion and increase their confidence in health decisions.