Logistic burdens of cancer care: A qualitative study.

Cancer treatment often creates logistic conflicts with everyday life priorities; however, these challenges and how they are subjectively experienced have been largely unaddressed in cancer care. Our goal was to describe time and logistic requirements of cancer care and whether and how they interfered with daily life and well-being. We conducted interviews with 20 adults receiving cancer-directed treatment at a single academic cancer center. We focused on participants' perception of the time, effort, and energy-intensiveness of cancer care activities, organization of care requirements, and preferences in how to manage the logistic burdens of their cancer care. Participant interview transcripts were analyzed using an inductive thematic analysis approach. Burdens related to travel, appointment schedules, healthcare system navigation, and consequences for relationships had roots both at the system-level (e.g. labs that were chronically delayed, protocol-centered rather than patient-centered bureaucratic requirements) and in individual circumstances (e.g. greater stressors among those working and/or have young children versus those who are retired) that determined subjective burdensomeness, which was highest among patients who experienced multiple sources of burdens simultaneously. Our study illustrates how objective burdens of cancer care translate into subjective burden depending on patient circumstances, emphasizing that to study burdens of care, an exclusive focus on objective measures does not capture the complexity of these issues. The complex interplay between healthcare system factors and individual circumstances points to clinical opportunities, for example helping patients to find ways to meet work and childcare requirements while receiving care.

A pilot randomized controlled trial of an online intervention for Hodgkin lymphoma survivors to increase knowledge about late effects and recommended screening.

BACKGROUND: Hodgkin lymphoma (HL) survivors who received chest radiotherapy are at risk for breast cancer and cardiovascular disease, but screening adherence is low. We assessed the acceptability/feasibility of a web-based educational intervention and its impact on knowledge of health risks and screening. METHODS: HL survivors were randomized to either an interactive online educational intervention or handouts only. Surveys were completed at baseline and 3 months post-intervention. We described the acceptability/feasibility of the intervention and compared knowledge between groups. RESULTS: Fifty-two HL survivors participated; 27 in the intervention group and 25 in the control group. Eighteen (66%) intervention participants completed the intervention and reported high acceptability (89-100%). At baseline, adherence to breast cancer screening was low across all participants. Post-intervention, those in the intervention group more often than controls correctly identified breast cancer and echocardiogram screening guidelines (35% vs. 28%, P = 0.02 and 82% vs. 52%, P = 0.04) and reported knowing how to address potential complications from cancer treatments (87% vs. 64%, P = 0.03). We detected no increase in screening behavior post-intervention. CONCLUSION: Online education modules for high-risk HL survivors are an acceptable method to improve knowledge of health risks and screening guidelines. Future interventions should focus on improving screening uptake in this population. IMPLICATIONS FOR CANCER SURVIVORS: Web-based learning can be useful in increasing cancer survivor knowledge of their unique risks and screening recommendations but does not necessarily change patient behavior. Involvement in a cancer survivorship program can help assess individual barriers and monitor uptake of screening.

Health Care Contact Days Among Older Cancer Survivors.

PURPOSE: Health care contact days-days spent receiving health care outside the home-represent an intuitive, practical, and person-centered measure of time consumed by health care. METHODS: We linked 2019 Medicare Current Beneficiary Survey and traditional Medicare claims data for community-dwelling older adults with a history of cancer. We identified contact days (ie, spent in a hospital, emergency department, skilled nursing facility, or inpatient hospice or receiving ambulatory care including an office visit, procedure, treatment, imaging, or test) and described patterns of total and ambulatory contact days. Using weighted Poisson regression models, we identified factors associated with contact days. RESULTS: We included 1,168 older adults representing 4.51 million cancer survivors (median age, 76.4 years, 52.8% women). The median (IQR) time from cancer diagnosis was 65 (27-126) months. In 2019, these adults had mean (standard deviation) total contact days of 28.4 (27.6) and ambulatory contact days of 24.2 (23.6). These included days for tests (8.0 [8.8]), imaging (3.6 [4.1]), visits with any clinicians (12.4 [11.5]), and visits with primary care clinicians (4.4 [4.7]), and nononcology specialists (7.1 [9.4]) specifically. Sixty-four percent of days with a nonvisit ambulatory service (eg, a test) were not on the same day as a clinician visit. Factors associated with more total contact days included younger age, lower income, more chronic conditions, poor self-rated health, and tendency to "go to doctor as soon as feel bad." CONCLUSION: Older adult cancer survivors spent nearly 1 month of the year receiving health care outside the home. This care was largely ambulatory, often delivered by nononcologists, and varied by factors beyond clinical characteristics. These results highlight the need to recognize patient burdens and improve survivorship care delivery, including through care coordination.

Comparisons of financial hardship in cancer care by family structure and among those with and without minor children using nationally representative data.

INTRODUCTION: While demographic risk factors of cancer-related financial hardships have been studied, having minor children or being single have rarely been assessed in the context of healthcare-related financial hardships. METHODS: Using data from the 2015 to 2018 National Health Interview Survey, we assessed financial hardship (material and psychological hardship; behavioral coping due to costs: delaying/foregoing care, reducing prescription costs, or skipping specialists or follow-up care) among adults aged 18-59 years with cancer (N = 2844) by minor child parenting status and family structure. In a secondary analysis, we compared this group with individuals without cancer. Using logistic regression models, we compared those with and without children aged <18 years, further distinguishing between those who were single versus one of two or more adults in the family. RESULTS: Compared to individuals from families with two or more adults/without children, single adults with children more often reported cancer-related financial hardships, for example material hardship (45.9% vs. 38.8%), and reducing prescription costs, (50.7% vs. 34.4%, adjusted OR 1.57, 95% CI 1.07-2.28). Single adults without minor children and those from families with two or more adults/with minor children also reported greater financial hardships on some dimensions. Associations were similar among those without cancer, but the overall magnitude of financial hardships was lower compared to those with cancer. CONCLUSIONS: Our findings suggest that having minor children, and being a single adult are risk factors for cancer-related financial hardship. Financial vulnerability associated with family structure should be taken into consideration in healthcare, and especially cancer care.

Rural-urban differences in meeting of physical activity recommendations by sun exposure and protection behaviors in the United States.

OBJECTIVE: To examine associations between sun protection behaviors and physical activity (PA) by rural and urban residence in the United States. METHODS: We analyzed data from the National Health and Nutrition Examination Survey (2013-2018), restricting to participants ages 20-59 with sun behavior data. Sunburns, sun exposure, and sun protection measures were dichotomized (yes/no): ≥1 sunburn in the past year, 2+ hour outside during workdays or non-workdays, and never/rarely/sometimes using sunscreen, wearing long sleeves, and staying in the shade. Meeting PA recommendations (yes/no) was defined as ≥150 min of vigorous/moderate or ≥ 75 min vigorous PA per week. Associations between sun behaviors and PA were analyzed using logistic regression models, which accounted for survey-weights and potential confounders, and stratified by rural-urban status. RESULTS: Rural and urban individuals meeting PA recommendations had greater odds of spending 2+ hour outside during workdays (OR: 2.26 [1.88, 2.74] and 3.95 [2.72, 5.73]) and non-workdays (OR: 2.06 [1.78, 2.38] and 3.33 [2.47, 4.46]). Among urban residents, odds of staying in the shade were lower among those who met PA recommendations (OR: 0.78 [0.66, 0.92]). We did not observe differences in sunburns or other sun behaviors by PA status, regardless of rurality. CONCLUSIONS: Meeting PA recommendations was associated with greater sun exposure in both rural and urban populations. Additional exercise location (indoors/outside) data is needed to inform PA and skin cancer prevention interventions to reduce unintended increases in sun exposure and reductions in PA, respectively, especially among rural populations.

Consuming Patients' Days: Time Spent on Ambulatory Appointments by People With Cancer.

BACKGROUND: In qualitative work, patients report that seemingly short trips to clinic (eg, a supposed 10-minute blood draw) often turn into "all-day affairs." We sought to quantify the time patients with cancer spend attending ambulatory appointments. METHODS: We conducted a retrospective study of patients scheduled for oncology-related ambulatory care (eg, labs, imaging, procedures, infusions, and clinician visits) at an academic cancer center over 1 week. The primary exposure was the ambulatory service type(s) (eg, clinician visit only, labs and infusion, etc.). We used Real-Time Location System badge data to calculate clinic times and estimated round-trip travel times and parking times. We calculated and summarized clinic and total (clinic + travel + parking) times for ambulatory service types. RESULTS: We included 435 patients. Across all service day type(s), the median (IQR) clinic time was 119 (78-202) minutes. The estimated median (IQR) round-trip driving distance and travel time was 34 (17-49) miles and 50 (36-68) minutes. The median (IQR) parking time was 14 (12-15) minutes. Overall, the median (IQR) total time was 197 (143-287) minutes. The median total times for specific service type(s) included: 99 minutes for lab-only, 144 minutes for clinician visit only, and 278 minutes for labs, clinician visit, and infusion. CONCLUSION: Patients often spent several hours pursuing ambulatory cancer care on a given day. Accounting for opportunity time costs and the coordination of activities around ambulatory care, these results highlight the substantial time burdens of cancer care, and support the notion that many days with ambulatory health care contact may represent "lost days."

Rural-Urban Differences in Sun Exposure and Protection Behaviors in the United States.

BACKGROUND: Evidence regarding whether rural residence is a risk factor for skin cancer is mixed. We compared sun exposure and protection behaviors between rural and urban residents by ethno-racial group in the United States. METHODS: We analyzed data from three (2013-2018) National Health and Nutrition Examination Survey cycles. We compared self-reported sun exposure and protection measures (sunburn, time spent outside, sunscreen use, wearing long sleeves, staying in shade) by rural-urban residential status using survey-weighted logistic regression models stratified by ethno-racial group, adjusting for age, sex, income, education, body mass index, and smoking. RESULTS: Hispanic rural versus urban residents more often reported sunburns in the past year [41.6% vs. 31.2%, adjusted OR (aOR): 1.46 (1.15-1.86)]. White rural versus urban residents more often spent 2+ hours outside on workdays [42.9% vs. 29.1%, aOR: 1.60 (1.27-2.01)] and non-workdays [72.2% vs. 64.8%, aOR: 1.45 (1.12-1.88)] and less often used sunscreen [26.0% vs. 35.1%, aOR: 0.74 (0.59-0.93)] and stayed in the shade [21.7% vs. 26.7%, aOR: 0.72 (0.57-0.89)]. Black rural versus urban residents stayed in the shade less often [31.6% vs. 43.9%, aOR: 0.60 (0.39-0.91)] but less often spent 2+ hours outside on non-workdays [47.6% vs. 56.8%, aOR: 0.67 (0.51-0.90)]. CONCLUSIONS: Across all ethno-racial groups included, rural residents reported greater sun risk behaviors than urban residents, with some nuances by ethno-racial identity, suggesting rural residence is a potential risk factor for skin cancer. IMPACT: Sun protection promotion programs should consider rural-urban settings while also accounting for ethno-racial identities.

Quantification of low-level human cytomegalovirus and Epstein-Barr virus DNAemia by digital PCR.

BACKGROUND: Digital PCR (dPCR) can quantify cell-free viral DNA (DNAemia), a biomarker of active viral infection. To accelerate epidemiologic investigation into low-level viral reactivation in chronic disease, we have evaluated the performance of dPCR to detect cytomegalovirus (CMV) and Epstein-Barr virus (EBV) DNAemia across platforms and blood matrices. METHODS: The droplet-based (BioRad) dPCR platform performance was compared to chip-based (BioMark), and assay validation followed dMIQE guidelines. CMV and EBV DNA reference materials were spiked into known negative plasma and serum samples. In addition, two independent cohorts of ovarian cancer patients were evaluated for viral DNAemia (n = 65 serum and 79 plasma samples). RESULTS: The limit of quantification (LOQ) was at or slightly above 100 copies/mL for both instruments: 105-135 copies/mL for droplet-based detection and 100 copies/mL for chip-based detection. DNAemia in serum had a slightly lower LOQ (105-110 copies/mL) compared to plasma (LOQ; 115-135 copies/mL). The variation (CV) coefficients for each assay and machine were less than 5 %. In patient samples, CVs ranged from 4.5 - 7.4 % and were similar for cell-free DNA derived from serum or plasma. There was good correlation between DNAemia measurements in patient samples across dPCR platforms (r > 0.90 for each assay and matrix). CONCLUSION: dPCR can quantify low-level herpes virus DNAemia with CVs below 8 %. Our results indicate that using serum-derived cell-free DNA and droplet-based dPCR is optimal for quantitating low-level viral DNAemia; however, plasma and chip-based approaches are acceptable alternatives and suitable for epidemiologic investigation.

Treatment with tumor-treating fields (TTFields) suppresses intercellular tunneling nanotube formation in vitro and upregulates immuno-oncologic biomarkers in vivo in malignant mesothelioma.

Disruption of intercellular communication within tumors is emerging as a novel potential strategy for cancer-directed therapy. Tumor-Treating Fields (TTFields) therapy is a treatment modality that has itself emerged over the past decade in active clinical use for patients with glioblastoma and malignant mesothelioma, based on the principle of using low-intensity alternating electric fields to disrupt microtubules in cancer cells undergoing mitosis. There is a need to identify other cellular and molecular effects of this treatment approach that could explain reported increased overall survival when TTFields are added to standard systemic agents. Tunneling nanotube (TNTs) are cell-contact-dependent filamentous-actin-based cellular protrusions that can connect two or more cells at long-range. They are upregulated in cancer, facilitating cell growth, differentiation, and in the case of invasive cancer phenotypes, a more chemoresistant phenotype. To determine whether TNTs present a potential therapeutic target for TTFields, we applied TTFields to malignant pleural mesothelioma (MPM) cells forming TNTs in vitro. TTFields at 1.0 V/cm significantly suppressed TNT formation in biphasic subtype MPM, but not sarcomatoid MPM, independent of effects on cell number. TTFields did not significantly affect function of TNTs assessed by measuring intercellular transport of mitochondrial cargo via intact TNTs. We further leveraged a spatial transcriptomic approach to characterize TTFields-induced changes to molecular profiles in vivo using an animal model of MPM. We discovered TTFields induced upregulation of immuno-oncologic biomarkers with simultaneous downregulation of pathways associated with cell hyperproliferation, invasion, and other critical regulators of oncogenic growth. Several molecular classes and pathways coincide with markers that we and others have found to be differentially expressed in cancer cell TNTs, including MPM specifically. We visualized short TNTs in the dense stromatous tumor material selected as regions of interest for spatial genomic assessment. Superimposing these regions of interest from spatial genomics over the plane of TNT clusters imaged in intact tissue is a new method that we designate Spatial Profiling of Tunneling nanoTubes (SPOTT). In sum, these results position TNTs as potential therapeutic targets for TTFields-directed cancer treatment strategies. We also identified the ability of TTFields to remodel the tumor microenvironment landscape at the molecular level, thereby presenting a potential novel strategy for converting tumors at the cellular level from 'cold' to 'hot' for potential response to immunotherapeutic drugs.

Prevalence of active cytomegalovirus infection at diagnosis of ovarian cancer and during chemotherapy and subsequent changes in cognitive functioning.

PURPOSE: One of the most frequently reported effects of cancer and its treatments is cancer-related cognitive impairment (CRCI). Viral infections may affect inflammation and immune function and therefore may influence patient symptoms, including CRCI. The goal of this study was to describe the prevalence of cytomegalovirus (CMV) infections at diagnosis, during, and after chemotherapy in individuals with ovarian cancer and explore CMV infection at diagnosis with cancer-related cognitive impairment (CRCI) following chemotherapy. METHODS: We recruited adults newly diagnosed with ovarian, primary peritoneal or fallopian tube cancer at a single academic cancer center into two prospective studies. In Study 1 (N = 71), participants provided blood samples at diagnosis. In Study 2 (N = 18), participants provided blood samples and completed symptom surveys before, during and after front-line adjuvant chemotherapy. Serum CMV DNA levels were assessed using digital PCR; >100 copies/mL of serum was considered positive for active CMV infection (CMV+). CRCI was measured using the Functional Assessment of Cancer Therapy - Cognitive Function (FACT-Cog) questionnaire. Changes in FACT-Cog scores were compared by CMV status at diagnosis using t-tests at each time point. RESULTS: At diagnosis, 29.2% were CMV+ (28.2% in Study 1, 33.3% in Study 2). Following three cycles of chemotherapy (Study 2), CMV positivity rose to 60.0% and then back down to 31.3% after chemotherapy. We observed significant differences in CRCI following chemotherapy by CMV status at diagnosis. CONCLUSION: Our data suggest that active CMV infection is common among patients undergoing treatment for ovarian cancer and may contribute to symptoms of CRCI.

Human APOBEC3B promotes tumor development in vivo including signature mutations and metastases.

The antiviral DNA cytosine deaminase APOBEC3B has been implicated as a source of mutation in many cancers. However, despite years of work, a causal relationship has yet to be established in vivo. Here, we report a murine model that expresses tumor-like levels of human APOBEC3B. Animals expressing full-body APOBEC3B appear to develop normally. However, adult males manifest infertility, and older animals of both sexes show accelerated rates of carcinogenesis, visual and molecular tumor heterogeneity, and metastasis. Both primary and metastatic tumors exhibit increased frequencies of C-to-T mutations in TC dinucleotide motifs consistent with the established biochemical activity of APOBEC3B. Enrichment for APOBEC3B-attributable single base substitution mutations also associates with elevated levels of insertion-deletion mutations and structural variations. APOBEC3B catalytic activity is required for all of these phenotypes. Together, these studies provide a cause-and-effect demonstration that human APOBEC3B is capable of driving both tumor initiation and evolution in vivo.

Sustaining positive perceptions of science in the face of conflicting health information: An experimental test of messages about the process of scientific discovery.

BACKGROUND: The public is often exposed to conflicting health information, with evidence of concerning consequences, yet little attention has been paid to identifying strategies that can mitigate its effects. OBJECTIVE: The current study tests whether three different approaches to communicating about the process of scientific discovery-a rational appeal using analogical evidence, a rational appeal using testimonial evidence, and a logic-based inoculation approach-could reduce the adverse effects of exposure to conflict by positively framing how people construe the scientific process, increasing their perceived knowledge about the scientific process, and helping them to respond to critiques about the scientific process, which, in turn, might make them less apt to counterargue the science they subsequently encounter in health news stories and other exposures to conflict. METHODS: We fielded a survey experiment in May 2022 with a national sample of U.S. adults (N = 1604). RESULTS: Providing any of the three messages about science prior to exposure to conflicting health information encouraged both positive construal of science and greater science knowledge perceptions and discouraged counterarguing science, compared to a control condition in which people were only exposed to conflict. Of the three messaging approaches tested, the testimonial evidence message was slightly more effective, but was also considered slightly more accurate, credible, and trustworthy. CONCLUSIONS: Developing and implementing messages that describe the process of scientific discovery could prove successful, not only in improving public perceptions of science but perhaps ultimately in better equipping people to make sense of conflicting information and its causes. However, additional research on such strategies is needed, particularly as part of larger interventions with multiple messages across multiple exposures, if they are to have implications for health and science communication.

Health Care Contact Days Experienced by Decedents With Advanced GI Cancer.

PURPOSE: Frequent visits to health care facilities can be time intensive and all-consuming for people with cancer. We measured health care contact days (days with healthcare contact outside the home) among decedents with advanced GI cancer and examined sources of contact days, their associations with demographic and clinical factors, and their temporal patterns over the course of illness. METHODS: We conducted a retrospective cohort study using a tumor registry and electronic medical record data for decedents with stage IV GI cancer between 2011 and 2019 in a large health care network in MN. We determined contact days from diagnosis to death using chart review. Using multivariable beta regression adjusted for sociodemographic and clinical characteristics offset by survival, we calculated adjusted estimates of contact days and determined patient-level factors associated with percentage of contact days. RESULTS: We identified 809 patients eligible for analysis (median [IQR] age at diagnosis, 65 [56-73] years). The median (IQR) overall survival was 175 (56-459) days. Patients spent a median (IQR) of 25.8% (17.4%-39.1%) of these as contact days. Of these days, 83.6% were spent on outpatient visits. In the multivariable analysis, older age, Black race, and never receiving systemic cancer-directed treatment were associated with a higher percentage of contact days. The percentage of contact days was highest in the first month after diagnosis (39.6%) and before death (32.2%), with a more moderate middle phase (U-shaped curve). CONCLUSION: Decedents with advanced GI cancer spend 1 in 4 days alive with health care contact, despite a median survival of under 6 months. This is even higher immediately postdiagnosis and near death. These findings highlight the need to understand sources of variation, benchmark appropriate care, and deliver more efficient care for this vulnerable population with limited time.

Usability and Satisfaction Testing of Game-Based Learning Avatar-Navigated Mobile (GLAm), an App for Cervical Cancer Screening: Mixed Methods Study.

BACKGROUND: Barriers to cervical cancer screening in young adults include a lack of knowledge and negative perceptions of testing. Evidence shows that mobile technology reduces these barriers; thus, we developed a web app, Game-based Learning Avatar-navigated mobile (GLAm), to educate and motivate cervical cancer screening using the Fogg Behavioral Model as a theoretic guide. Users create avatars to navigate the app, answer short quizzes with education about cervical cancer and screening, watch videos of the screening process, and earn digital trophies. OBJECTIVE: We tested ease of use, usefulness, and satisfaction with the GLAm app among young adults. METHODS: This mixed methods study comprised a qualitative think-aloud play interview session and a quantitative survey study. Participants were cervical cancer screening-eligible US residents aged 21 to 29 years recruited through social media. Qualitative study participants explored the app in a think-aloud play session conducted through videoconference. Data were analyzed using directed content analysis to identify themes of ease of use, usefulness, and content satisfaction. Qualitative study participants and additional participants then used the app independently for 1 week and completed a web-based survey (the quantitative study). Ease of use, usefulness, and satisfaction were assessed using the validated Technology Acceptance Model and Computer System Usability Questionnaire adapted to use of an app. Mean (SD) scores (range 1-7) are presented. RESULTS: A total of 23 individuals participated in one or both study components. The mean age was 25.6 years. A majority were cisgender women (21/23, 91%) and White (18/23, 78%), and 83% (19/23) had at least some secondary education. Nine participants completed the think-aloud play session. Direct content analysis showed desire for content that is concise, eases anxiety around screenings, and uses game features (avatars and rewards). Twenty-three individuals completed the quantitative survey study. Mean scores showed the app was perceived to be easy to use (mean score 6.17, SD 0.27) and moderately useful to increase cervical cancer screening knowledge and uptake (mean score 4.94, SD 0.27). Participants were highly satisfied with the app (mean score 6.21, SD 1.20). CONCLUSIONS: Survey results showed participants were satisfied with the app format and found it easy to use. The app was perceived to be moderately useful to inform and motivate cervical cancer screening; notably, the screening reminder function was not tested in this study. Qualitative study results demonstrated the app's ability to ease anxiety about screening through demonstration of the screening process, and brevity of app components was favored. Interpretation of results is limited by the predominantly cisgender, White, and educated study population; additional testing in populations which historically have lower cervical cancer screening uptake is needed. A modified version of the app is undergoing efficacy testing in a randomized clinical trial.

DNA Deamination Is Required for Human APOBEC3A-Driven Hepatocellular Carcinoma In Vivo.

Although the APOBEC3 family of single-stranded DNA cytosine deaminases is well-known for its antiviral factors, these enzymes are rapidly gaining attention as prominent sources of mutation in cancer. APOBEC3's signature single-base substitutions, C-to-T and C-to-G in TCA and TCT motifs, are evident in over 70% of human malignancies and dominate the mutational landscape of numerous individual tumors. Recent murine studies have established cause-and-effect relationships, with both human APOBEC3A and APOBEC3B proving capable of promoting tumor formation in vivo. Here, we investigate the molecular mechanism of APOBEC3A-driven tumor development using the murine Fah liver complementation and regeneration system. First, we show that APOBEC3A alone is capable of driving tumor development (without Tp53 knockdown as utilized in prior studies). Second, we show that the catalytic glutamic acid residue of APOBEC3A (E72) is required for tumor formation. Third, we show that an APOBEC3A separation-of-function mutant with compromised DNA deamination activity and wildtype RNA-editing activity is defective in promoting tumor formation. Collectively, these results demonstrate that APOBEC3A is a "master driver" that fuels tumor formation through a DNA deamination-dependent mechanism.

Endothelial Dysfunction in Breast Cancer Survivors on Aromatase Inhibitors: Changes over Time.

Background: Aromatase inhibitors (AIs) are recommended as adjuvant treatment for estrogen-receptor positive breast carcinoma in postmenopausal women. Studies demonstrate mixed results as to the impact of AIs on cardiovascular (CV) events and overall survival. With the increasing number of pre- and postmenopausal women on AIs for five to ten years, understanding the long-term impact of AIs on blood vessels and CV risk in cancer survivors is vital. Methods: A single arm longitudinal study of 14 postmenopausal women with ER+ breast cancer prescribed adjuvant AIs at the University of Minnesota. Subjects with a history of tobacco use, hypertension, or hyperlipidemia were excluded. Participants underwent routine labs, blood pressure assessments, and vascular testing at baseline (prior to starting AIs) and at six months. Vascular assessment was performed using the EndoPAT 2000 and HDI/PulseWave CR-2000 Cardiovascular Pro ling System and pulse contour analysis on two occasions as previously described. Vascular measurements were conducted by one trained vascular technician. Assessments were performed in triplicate, and the mean indices were used for analyses. All subjects were on an AI at the follow-up visit. The protocol was approved by the UMN Institutional Review Board and all participants were provided written informed consent. Baseline and follow-up characteristics were compared using Wilcoxon signed-rank tests. Analyses were performed using R version 3.6.1 (R Foundation for Statistical Computing, Vienna, Austria). Results: After six months of AI treatment, EndoPAT® ratio declined to a median 1.12 (Q1: 0.85, Q3: 1.86; p=0.045) and median estradiol levels decreased to 2 pg/mL (Q1: 2, Q3: 3; p=0.052). There was no evidence of association between change in EndoPAT® and change in estradiol level (p=0.91). There were no statistically significant changes in small or large arterial elasticity. Conclusion: Endovascular dysfunction is an early sign for atherosclerosis and vascular impairment. This study suggests that postmenopausal breast cancer survivors on aromatase inhibitor therapy develop endothelial dysfunction as early as six months which is a predictor of adverse CV disease. We hypothesize that long-term use of AIs can lead to persistent endothelial dysfunction. It is unclear if these changes are reversible once AI use is discontinued and further investigation is necessary.

Human APOBEC3B promotes tumor heterogeneity in vivo including signature mutations and metastases.

The antiviral DNA cytosine deaminase APOBEC3B has been implicated as a source of mutation in many different cancers. Despite over 10 years of work, a causal relationship has yet to be established between APOBEC3B and any stage of carcinogenesis. Here we report a murine model that expresses tumor-like levels of human APOBEC3B after Cre-mediated recombination. Animals appear to develop normally with full-body expression of APOBEC3B. However, adult males manifest infertility and older animals of both sexes show accelerated rates of tumorigenesis (mostly lymphomas or hepatocellular carcinomas). Interestingly, primary tumors also show overt heterogeneity, and a subset spreads to secondary sites. Both primary and metastatic tumors exhibit increased frequencies of C-to-T mutations in TC dinucleotide motifs consistent with the established biochemical activity of APOBEC3B. Elevated levels of structural variation and insertion-deletion mutations also accumulate in these tumors. Together, these studies provide the first cause-and-effect demonstration that human APOBEC3B is an oncoprotein capable of causing a wide range of genetic changes and driving tumor formation in vivo .

Genetic variants associated with post-traumatic stress symptoms in patients with gynecologic cancer.

OBJECTIVE: Patients with cancer experience symptoms of post-traumatic stress disorder (PTSD) more commonly than the general population. The objective of this study was to identify single nucleotide polymorphisms (SNPs) associated with increased risk of post-traumatic stress disorder (PTSD) in patients with gynecologic cancer. METHODS: A prospective cohort study recruited 181 gynecologic cancer survivors receiving care at the University of Minnesota between 2017 and 2020 who completed PTSD DSM-V surveys to self-report their symptoms of PTSD and provided saliva samples. DNA samples were genotyped for 11 SNPs in 9 genes involved in dopaminergic, serotonergic, and opioidergic systems previously associated with risk of PTSD in populations without cancer. RESULTS: Most participants had either ovarian (42.5%) or endometrial (46.4%) cancer; fewer had cervical (7.7%) or vaginal/vulvar (3.3%) cancer. Two SNPS were identified as statistically significantly associated with higher PTSD scores: rs622337 in HTR2A and rs510769 in OPRM1. CONCLUSIONS: Genetic variation likely plays a role in development of PTSD. HTR2A is involved in the serotonin pathway, and OPRM1 is involved in the opioid receptor pathway. This information can be used by oncologic providers to identify patients at greater risk of developing PTSD and may facilitate referral to appropriate consultants and resources early in their treatment.

Incidental sun exposures as a source of sunburn among rural compared to urban residents in the United States.

PURPOSE: Melanoma incidence is higher in rural than in urban areas in the United States, possibly due to greater incidental sun exposures from rural outdoor-focused lifestyles and occupational patterns. Our aim was to compare activities at the time of a sunburn between rural and urban residents. METHODS: Utilizing the nationally representative 2019 cross-sectional Health Information National Trends Survey (HINTS), we report odds ratios (OR) and confidence intervals (CI) from logistic regression models comparing self-reported activities at most recent sunburn among rural versus urban adults. FINDINGS: About one-third of participants (37.2%) reported a sunburn in the past year, higher in urban (38.0%) than in rural populations (32.5%). At the time of most recent sunburn, swimming (36.6%) and working outside a home (29.4%) were the most commonly reported activities. Working on a job (30.4% vs 10.4%; OR: 3.30, 95% CI: 1.33, 8.20) or outside the house (38.7% vs 28.1%; OR: 1.86, 95% CI: 1.03, 3.33) were more common, while exercising or sunbathing were less common, among rural compared to urban participants. CONCLUSIONS: Incidental sun exposures during outdoor-focused rural occupations and work outside the house may be critical skin cancer prevention targets in rural populations; outdoor exercise and sunbathing may be more important in urban populations; incidental exposures while swimming may be important in both populations.

Cross-sectional study of physical activity among long-term melanoma survivors and population controls.

Physical activity has been associated with improved outcomes among cancer survivors of various malignancies; however, this topic is understudied among melanoma survivors. Our objective was to determine whether long-term melanoma survivors are less likely to meet American Cancer Society physical activity guidelines than non-melanoma population controls. We conducted a cross-sectional survey in 2015 to follow up participants from a case-control study of melanoma and population controls in Minnesota. The primary outcome was meeting American Cancer Society recommendations for healthy physical activity levels. Physical activity, sun protection practices and time spent outside were compared between survivors and controls using generalized linear regression models. Melanoma survivors (N = 724) and controls (N = 639) were similar with the exceptions of daily hours spent outside, sun protection scores, skin tone, and smoking status. Half (50.8%) of melanoma survivors reported meeting the physical activity guidelines, compared to 39.7% of controls (p < 0.0001), with an 11% (95% CI 0.05-0.17) difference after adjusting for potential confounders. While long-term melanoma survivors were more likely to meet American Cancer Society physical activity guidelines than population controls, nearly 50% did not meet recommendations. This finding is concerning given the known improvements in quality of life and survival among physically active cancer survivors. Opportunities remain to promote physical activity among melanoma survivors. Health communications that promote outdoor exercise, in particular, should include advice about sun protection.