Collaborative Modeling to Compare Different Breast Cancer Screening Strategies: A Decision Analysis for the US Preventive Services Task Force.

Importance: The effects of breast cancer incidence changes and advances in screening and treatment on outcomes of different screening strategies are not well known. Objective: To estimate outcomes of various mammography screening strategies. Design, Setting, and Population: Comparison of outcomes using 6 Cancer Intervention and Surveillance Modeling Network (CISNET) models and national data on breast cancer incidence, mammography performance, treatment effects, and other-cause mortality in US women without previous cancer diagnoses. Exposures: Thirty-six screening strategies with varying start ages (40, 45, 50 years) and stop ages (74, 79 years) with digital mammography or digital breast tomosynthesis (DBT) annually, biennially, or a combination of intervals. Strategies were evaluated for all women and for Black women, assuming 100% screening adherence and "real-world" treatment. Main Outcomes and Measures: Estimated lifetime benefits (breast cancer deaths averted, percent reduction in breast cancer mortality, life-years gained), harms (false-positive recalls, benign biopsies, overdiagnosis), and number of mammograms per 1000 women. Results: Biennial screening with DBT starting at age 40, 45, or 50 years until age 74 years averted a median of 8.2, 7.5, or 6.7 breast cancer deaths per 1000 women screened, respectively, vs no screening. Biennial DBT screening at age 40 to 74 years (vs no screening) was associated with a 30.0% breast cancer mortality reduction, 1376 false-positive recalls, and 14 overdiagnosed cases per 1000 women screened. Digital mammography screening benefits were similar to those for DBT but had more false-positive recalls. Annual screening increased benefits but resulted in more false-positive recalls and overdiagnosed cases. Benefit-to-harm ratios of continuing screening until age 79 years were similar or superior to stopping at age 74. In all strategies, women with higher-than-average breast cancer risk, higher breast density, and lower comorbidity level experienced greater screening benefits than other groups. Annual screening of Black women from age 40 to 49 years with biennial screening thereafter reduced breast cancer mortality disparities while maintaining similar benefit-to-harm trade-offs as for all women. Conclusions: This modeling analysis suggests that biennial mammography screening starting at age 40 years reduces breast cancer mortality and increases life-years gained per mammogram. More intensive screening for women with greater risk of breast cancer diagnosis or death can maintain similar benefit-to-harm trade-offs and reduce mortality disparities.

Need for Culturally Competent and Responsive Cancer Education for African Immigrant Families and Youth Living in the United States.

Cancer prevalence data for Black Americans is monolithic and fails to consider the diverse cultures and backgrounds within that community. For instance, African immigrants constitute a meaningful proportion of the foreign-born Black immigrants in the United States (42%), but the prevalence of cancer in the African immigrant community itself is unknown. Therefore, without accurate cancer prevalence data, it is impossible to identify trends and other key factors that are needed to support the health of African immigrants and their children. Moreover, it is impossible to understand how the culture and language of subgroups influence their cancer-related health behavior. While research in this area is limited, the existing literature articulates the need for culturally responsive and culturally tailored cancer education for African immigrants and their adolescent children, which is what we advocate for in this viewpoint paper. Existing projects demonstrate the feasibility of culturally responsive programming for adults; however, few projects include or focus on adolescents or children born to African immigrants. To best meet the needs of this understudied community, researchers must use culturally competent interventions alongside familiar, usable media. For adolescents, technology is ubiquitous thus, the creation of a culturally tailored digital intervention has immense potential to improve cancer awareness and prevention for youth and their community. More research is needed to address many of the existing research gaps and develop a rich understanding of the unique experience of cancer among African immigrant families that can be used to inform intervention development. Through this viewpoint, we review the current state of cancer-related research among African immigrant families in the United States. In this paper, we acknowledge the current knowledge gaps and issues surrounding measurement and then discuss the factors relevant to designing an educational intervention targeted at African immigrants and the role of African immigrant youth.

Analysis of Breast Cancer Mortality in the US-1975 to 2019.

Importance: Breast cancer mortality in the US declined between 1975 and 2019. The association of changes in metastatic breast cancer treatment with improved breast cancer mortality is unclear. Objective: To simulate the relative associations of breast cancer screening, treatment of stage I to III breast cancer, and treatment of metastatic breast cancer with improved breast cancer mortality. Design, Setting, and Participants: Using aggregated observational and clinical trial data on the dissemination and effects of screening and treatment, 4 Cancer Intervention and Surveillance Modeling Network (CISNET) models simulated US breast cancer mortality rates. Death due to breast cancer, overall and by estrogen receptor and ERBB2 (formerly HER2) status, among women aged 30 to 79 years in the US from 1975 to 2019 was simulated. Exposures: Screening mammography, treatment of stage I to III breast cancer, and treatment of metastatic breast cancer. Main Outcomes and Measures: Model-estimated age-adjusted breast cancer mortality rate associated with screening, stage I to III treatment, and metastatic treatment relative to the absence of these exposures was assessed, as was model-estimated median survival after breast cancer metastatic recurrence. Results: The breast cancer mortality rate in the US (age adjusted) was 48/100 000 women in 1975 and 27/100 000 women in 2019. In 2019, the combination of screening, stage I to III treatment, and metastatic treatment was associated with a 58% reduction (model range, 55%-61%) in breast cancer mortality. Of this reduction, 29% (model range, 19%-33%) was associated with treatment of metastatic breast cancer, 47% (model range, 35%-60%) with treatment of stage I to III breast cancer, and 25% (model range, 21%-33%) with mammography screening. Based on simulations, the greatest change in survival after metastatic recurrence occurred between 2000 and 2019, from 1.9 years (model range, 1.0-2.7 years) to 3.2 years (model range, 2.0-4.9 years). Median survival for estrogen receptor (ER)-positive/ERBB2-positive breast cancer improved by 2.5 years (model range, 2.0-3.4 years), whereas median survival for ER-/ERBB2- breast cancer improved by 0.5 years (model range, 0.3-0.8 years). Conclusions and Relevance: According to 4 simulation models, breast cancer screening and treatment in 2019 were associated with a 58% reduction in US breast cancer mortality compared with interventions in 1975. Simulations suggested that treatment for stage I to III breast cancer was associated with approximately 47% of the mortality reduction, whereas treatment for metastatic breast cancer was associated with 29% of the reduction and screening with 25% of the reduction.

Data gaps and opportunities for modeling cancer health equity.

Population models of cancer reflect the overall US population by drawing on numerous existing data resources for parameter inputs and calibration targets. Models require data inputs that are appropriately representative, collected in a harmonized manner, have minimal missing or inaccurate values, and reflect adequate sample sizes. Data resource priorities for population modeling to support cancer health equity include increasing the availability of data that 1) arise from uninsured and underinsured individuals and those traditionally not included in health-care delivery studies, 2) reflect relevant exposures for groups historically and intentionally excluded across the full cancer control continuum, 3) disaggregate categories (race, ethnicity, socioeconomic status, gender, sexual orientation, etc.) and their intersections that conceal important variation in health outcomes, 4) identify specific populations of interest in clinical databases whose health outcomes have been understudied, 5) enhance health records through expanded data elements and linkage with other data types (eg, patient surveys, provider and/or facility level information, neighborhood data), 6) decrease missing and misclassified data from historically underrecognized populations, and 7) capture potential measures or effects of systemic racism and corresponding intervenable targets for change.

Population simulation modeling of disparities in US breast cancer mortality.

BACKGROUND: Populations of African American or Black women have persistently higher breast cancer mortality than the overall US population, despite having slightly lower age-adjusted incidence. METHODS: Three Cancer Intervention and Surveillance Modeling Network simulation teams modeled cancer mortality disparities between Black female populations and the overall US population. Model inputs used racial group-specific data from clinical trials, national registries, nationally representative surveys, and observational studies. Analyses began with cancer mortality in the overall population and sequentially replaced parameters for Black populations to quantify the percentage of modeled breast cancer morality disparities attributable to differences in demographics, incidence, access to screening and treatment, and variation in tumor biology and response to therapy. RESULTS: Results were similar across the 3 models. In 2019, racial differences in incidence and competing mortality accounted for a net ‒1% of mortality disparities, while tumor subtype and stage distributions accounted for a mean of 20% (range across models = 13%-24%), and screening accounted for a mean of 3% (range = 3%-4%) of the modeled mortality disparities. Treatment parameters accounted for the majority of modeled mortality disparities: mean = 17% (range = 16%-19%) for treatment initiation and mean = 61% (range = 57%-63%) for real-world effectiveness. CONCLUSION: Our model results suggest that changes in policies that target improvements in treatment access could increase breast cancer equity. The findings also highlight that efforts must extend beyond policies targeting equity in treatment initiation to include high-quality treatment completion. This research will facilitate future modeling to test the effects of different specific policy changes on mortality disparities.

Change in alcohol consumption during the Covid-19 pandemic and associations with mental health and financial hardship: results from a survey of Wisconsin patients with cancer.

PURPOSE: Alcohol consumption increases health risks for patients with cancer. The Covid-19 pandemic may have affected drinking habits for these individuals. We surveyed patients with cancer to examine whether changes in drinking habits were related to mental health or financial effects of the pandemic. METHODS: From October 2020 to April 2021, adult patients (age 18-80 years at diagnosis) treated for cancer in southcentral Wisconsin were invited to complete a survey. Age-adjusted percentages for history of anxiety or depression, emotional distress, and financial impacts of Covid-19 overall and by change in alcohol consumption (non-drinker, stable, decreased, or increased) were obtained via logistic regression. RESULTS: In total, 1,875 patients were included in the analysis (median age 64, range 19-87 years), including 9% who increased and 23% who decreased drinking. Compared to stable drinkers (32% of sample), a higher proportion of participants who increased drinking alcohol also reported anxiety or depression (45% vs. 26%), moderate to severe emotional distress (61% vs. 37%) and viewing Covid-19 as a threat to their community (67% vs. 55%). Decreased (vs. stable) drinking was associated with higher prevalence of depression or anxiety diagnosis, emotional distress, and negative financial impacts of the pandemic. Compared to non-drinkers (36% of sample), participants who increased drinking were more likely to report emotional distress (61% vs. 48%). CONCLUSIONS: Patients with cancer from Wisconsin who changed their alcohol consumption during the Covid-19 pandemic were more likely to report poor mental health including anxiety, depression, and emotional distress than persons whose alcohol consumption was stable. IMPLICATIONS FOR CANCER SURVIVORS: Clinicians working with cancer survivors should be aware of the link between poor mental health and increased alcohol consumption and be prepared to offer guidance or referrals to counseling, as needed.

Estimated US Cancer Deaths Prevented With Increased Use of Lung, Colorectal, Breast, and Cervical Cancer Screening.

Importance: Increased use of recommended screening could help achieve the Cancer Moonshot goal of reducing US cancer deaths. Objective: To estimate the number of cancer deaths that could be prevented with a 10-percentage point increase in the use of US Preventive Services Task Force (USPSTF)-recommended screening. Design, Setting, and Participants: This decision analytical model study is an extension of previous studies conducted for the USPSTF from 2018 to 2023. This study simulated contemporary cohorts of US adults eligible for lung, colorectal, breast, and cervical cancer screening. Exposures: Annual low-dose computed lung tomography among eligible adults aged 50 to 80 years; colonoscopy every 10 years among adults aged 45 to 75 years; biennial mammography among female adults aged 40 to 74 years; and triennial cervical cytology screening among female adults aged 21 to 29 years, followed by human papillomavirus testing every 5 years from ages 30 to 65 years. Main Outcomes and Measures: Estimated number of cancer deaths prevented with a 10-percentage point increase in screening use, assuming screening commences at the USPSTF-recommended starting age and continues throughout the lifetime. Outcomes were presented 2 ways: (1) per 100 000 and (2) among US adults in 2021; and they were expressed among the target population at the age of screening initiation. For lung cancer, estimates were among those who will also meet the smoking eligibility criteria during their lifetime. Harms from increased uptake were also reported. Results: A 10-percentage point increase in screening use at the age that USPSTF recommended screening commences was estimated to prevent 226 lung cancer deaths (range across models within the cancer site, 133-332 deaths), 283 (range, 263-313) colorectal cancer deaths, 82 (range, 61-106) breast cancer deaths, and 81 (1 model; no range available) cervical cancer deaths over the lifetimes of 100 000 persons eligible for screening. These rates corresponded with an estimated 1010 (range, 590-1480) lung cancer deaths prevented, 11 070 (range, 10 280-12 250) colorectal cancer deaths prevented, 1790 (range, 1330-2310) breast cancer deaths prevented, and 1710 (no range available) cervical cancer deaths prevented over the lifetimes of eligible US residents at the recommended age to initiate screening in 2021. Increased uptake was also estimated to generate harms, including 100 000 (range, 45 000-159 000) false-positive lung scans, 6000 (range, 6000-7000) colonoscopy complications, 300 000 (range, 295 000-302 000) false-positive mammograms, and 348 000 (no range available) colposcopies over the lifetime. Conclusions and Relevance: In this decision analytical model study, a 10-percentage point increase in uptake of USPSTF-recommended lung, colorectal, breast, and cervical cancer screening at the recommended starting age was estimated to yield important reductions in cancer deaths. Achieving these reductions is predicated on ensuring equitable access to screening.

Time-specific impact of mono-benzyl phthalate (MBzP) and perfluorooctanoic acid (PFOA) on breast density of a Chilean adolescent Cohort.

INTRODUCTION: High mammographic density is among the strongest and most established predictors for breast cancer risk. Puberty, the period during which breasts undergo exponential mammary growth, is considered one of the critical stages of breast development for environmental exposures. Benzylbutyl phthalate (BBP) and perfluorooctanoic acid (PFOA) are pervasive endocrine disrupting chemicals that may increase hormone-sensitive cancers. Evaluating the potential impact of BBP and PFOA exposure on pubertal breast density is important to our understanding of early-life environmental influences on breast cancer etiology. OBJECTIVE: To prospectively assess the effect of biomarker concentrations of monobenzyl phthalate (MBzP) and PFOA at specific pubertal window of susceptibility (WOS) on adolescent breast density. METHOD: This study included 376 Chilean girls from the Growth and Obesity Cohort Study with data collection at four timepoints: Tanner breast stages 1 (B1) and 4 (B4), 1- year post- menarche (1YPM) and 2-years post-menarche (2YPM). Dual-energy X-ray absorptiometry was used to assess the absolute fibroglandular volume (FGV) and percent breast density (%FGV) at 2YPM. We used concentrations of PFOA in serum and MBzP in urine as an index of exposure to PFOA and BBP, respectively. Parametric G-formula was used to estimate the time-specific effects of MBzP and PFOA on breast density. The models included body fat percentage as a time-varying confounder and age, birthweight, age at menarche, and maternal education as fixed covariates. RESULTS: A doubling of serum PFOA concentration at B4 resulted in a non-significant increase in absolute FGV (ß:11.25, 95% confidence interval (CI): -0.28, 23.49)), while a doubling of PFOA concentration at 1YPM resulted in a decrease in % FGV (ß:-4.61, 95% CI: -7.45, -1.78). We observed no associations between urine MBzP and breast density measures. CONCLUSION: In this cohort of Latina girls, PFOA serum concentrations corresponded to a decrease in % FGV. No effect was observed between MBzP and breast density measures across pubertal WOS.

Building relationships to connect cancer researchers with community members: 'bench to community pipeline'.

PURPOSE: Partnerships between researchers and community members and organizations can offer multiple benefits for research relevance and dissemination. The goal of this project was to build infrastructure to create bidirectional relationships between University of Wisconsin Carbone Cancer Center (UWCCC) researchers and community educators in the Division of Extension, which connects the knowledge and resources of the university to communities across the state. METHODS: This project had three aims: (1) create linkages with Extension; (2) establish an in-reach program to educate and train researchers on the science of Community Outreach and Engagement (COE); and (3) identify and facilitate collaborative projects between scientists and communities. Survey and focus group-based needs assessments were completed with both researchers and Extension educators and program activity evaluations were conducted. RESULTS: Most Extension educators (71%) indicated a strong interest in partnering on COE projects. UWCCC faculty indicated interest in further disseminating their research, but also indicated barriers in connecting with communities. Outreach webinars were created and disseminated to community, a "COE in-reach toolkit" for faculty was created and a series of "speed networking" events were hosted to pair researchers and community. Evaluations indicated the acceptability and usefulness of these activities and supported continuation of collaborative efforts. CONCLUSION: Continued relationship and skill building, along with a sustainability plan, is critical to support the translation of basic, clinical, and population research to action in the community outreach and engagement context. Further incentives for faculty should be explored for the recruitment of basic scientists into community engagement work.

Current Approaches to Serving Catchment Areas in Cancer Centers: Insights from the Big Ten Cancer Research Consortium Population Science Working Group.

In 2021, the NCI issued updated guidance clarifying the mission and organizational structure for Community Outreach and Engagement (COE) for Cancer Center Support Grants. These guidelines outlined how cancer centers should address the cancer burden of the catchment area (CA) and define how COE would partner with the community to inform cancer research and implement programs to reduce the cancer burden. In this paper, the Common Elements Committee of the Population Science Working Group in the Big Ten Cancer Research Consortium describes their respective approaches to implementing these guidelines. We discuss our definitions and rationales for each CA, data sources used, and our approach to assessing the impact of COE efforts on the burden of cancer in our respective CA. Importantly, we describe methods of translating unmet CA needs into our cancer-relevant outreach activities, and cancer research addressing the needs of respective CAs. Implementing these new guidelines is a challenge, and we hope that sharing approaches and experiences will foster cross-center collaborations that may more effectively reduce the burden of cancer in the US and meet the mission of the NCI's Cancer Center Program.

Breast cancer risk for women with diabetes and the impact of metformin: A meta-analysis.

BACKGROUND: Diabetes mellitus has been associated with increased breast cancer (BC) risk; however, the magnitude of this effect is uncertain. This study focused on BC risk for women with type 2 diabetes mellitus (T2DM). METHODS: Two separate meta-analyses were conducted (1) to estimate the relative risk (RR) of BC for women with T2DM and (2) to evaluate the risk of BC for women with T2DM associated with the use of metformin, a common diabetes treatment. In addition, subgroup analyses adjusting for obesity as measured by body mass index (BMI) and menopausal status were also performed. Studies were identified via PubMed/Scopus database and manual search through April 2021. RESULTS: A total of 30 and 15 studies were included in the first and second meta-analyses, respectively. The summary RR of BC for women with T2DM was 1.15 (95% confidence interval [CI], 1.09-1.21). The subgroup analyses adjusting BMI and adjusting BMI and menopause resulted in a summary RR of 1.22 (95% CI, 1.15-1.30) and 1.20 (95% CI, 1.05-1.36), respectively. For women with T2DM, the summary RR of BC was 0.82 (95% CI, 0.60-1.12) for metformin users compared with nonmetformin users. CONCLUSIONS: Women with T2DM were more likely to be diagnosed with BC and this association was strengthened by adjusting for BMI and menopausal status. No statistically significant reduction of BC risk was observed among metformin users. IMPACT: These two meta-analyses can inform decision-making for women with type 2 diabetes regarding their use of metformin and the use of screening mammography for early detection of breast cancer.

Team Science Principles Enhance Cancer Care Delivery Quality Improvement: Interdisciplinary Implementation of Breast Cancer Screening Shared Decision Making.

PURPOSE: Implementing shared decision making (SDM), recommended in screening mammography by national guidelines for women age 40-49 years, faces challenges that innovations in quality improvement and team science (TS) are poised to address. We aimed to improve the effectiveness, patient-centeredness, and efficiency of SDM in primary care for breast cancer screening. METHODS: Our interdisciplinary team included primary and specialty care, psychology, epidemiology, communication science, engineering, and stakeholders (patients and clinicians). Over a 6-year period, we executed two iterative cycles of plan-do-study-act (PDSA) to develop, revise, and implement a SDM tool using TS principles. Patient and physician surveys and retrospective analysis of tool performance informed our first PDSA cycle. Patient and physician surveys, toolkit use, and clinical outcomes in the second PDSA cycle supported SDM implementation. We gathered team member assessments on the importance of individual TS activities. RESULTS: Our first PDSA cycle successfully generated a SDM tool called Breast Cancer Risk Estimator, deemed valuable by 87% of patients surveyed. Our second PDSA cycle increased Breast Cancer Risk Estimator utilization, from 2,000 sessions in 2017 to 4,097 sessions in 2019 while maintaining early-stage breast cancer diagnoses. Although TS activities such as culture, trust, and communication needed to be sustained throughout the project, shared goals, research/data infrastructure support, and leadership were more important earlier in the project and persisted in the later stages of the project. CONCLUSION: Combining rigorous quality improvement and TS principles can support the complex, interdependent, and interdisciplinary activities necessary to improve cancer care delivery exemplified by our implementation of a breast cancer screening SDM tool.

Treatment Inequity: Examining the Influence of Non-Hispanic Black Race and Ethnicity on Pancreatic Cancer Care and Survival in Wisconsin.

INTRODUCTION: We investigated race and ethnicity-based disparities in first course treatment and overall survival among Wisconsin pancreatic cancer patients. METHODS: We identified adults diagnosed with pancreatic adenocarcinoma in the Wisconsin Cancer Reporting System from 2004 through 2017. We assessed race and ethnicity-based disparities in first course of treatment via adjusted logistic regression and overall survival via 4 incremental Cox proportional hazards regression models. RESULTS: The study included 8,490 patients: 91.3% (n = 7,755) non-Hispanic White; 5.1% (n = 437) non-Hispanic Black, 1.8% (n = 151) Hispanic, 0.6% Native American (n = 53), and 0.6% Asian (n = 51) race and ethnicities. Non-Hispanic Black patients had lower odds of treatment than non-Hispanic White patients for full patient (OR, 0.52; 95% CI, 0.41-0.65) and Medicare cohorts (OR, 0.40; 95% CI, 0.29-0.55). Non-Hispanic Black patients had lower odds of receiving surgery than non-Hispanic White patients (full cohort OR, 0.67 [95% CI, 0.48-0.92]; Medicare cohort OR, 0.57 [95% CI, 0.34-0.93]). Non-Hispanic Black patients experienced worse survival than non-Hispanic White patients in the first 2 incremental Cox proportional hazard regression models (model II HR, 1.18; 95% CI, 1.06-1.31). After adding insurance and treatment course, non-Hispanic Black and non-Hispanic White patients experienced similar survival (HR, 0.98; 95% CI, 0.88-1.09). CONCLUSION: Non-Hispanic Black patients were almost 50% less likely to receive any treatment and 33% less likely to receive surgery than non-Hispanic White patients. After including treatment course, non-Hispanic Black and non-Hispanic White patient survival was similar. Increasing non-Hispanic Black patient treatment rates by addressing structural factors affecting treatment availability and employing culturally humble approaches to treatment discussions may mitigate these disparities.

A Flexible Method for Identifying Spatial Clusters of Breast Cancer Using Individual-Level Data.

Prior research has shown that cancer risk varies by geography, but scan statistics methods for identifying cancer clusters in case-control studies have been limited in their ability to identify multiple clusters and adjust for participant-level risk factors. We develop a method to identify geographic patterns of breast cancer odds using the Wisconsin Women's Health Study, a series of 5 population-based case-control studies of female Wisconsin residents aged 20-79 enrolled in 1988-2004 (cases=16,076, controls=16,795). We create sets of potential clusters by overlaying a 1 km grid over each county-neighborhood and enumerating a series of overlapping circles. Using a two-step approach, we fit a penalized binomial regression model to the number of cases and trials in each grid cell, penalizing all potential clusters by the least absolute shrinkage and selection operator (Lasso). We use BIC to select the number of clusters, which are included in a participant-level logistic regression model. We identify 15 geographic clusters, resulting in 23 areas of unique geographic odds ratios. After adjustment for known risk factors, confidence intervals narrowed but breast cancer odds ratios did not meaningfully change; one additional hotspot was identified. By considering multiple overlapping spatial clusters simultaneously, we discern gradients of spatial odds across Wisconsin.

A Framework for Equitable Partnerships to Promote Cancer Prevention and Control in Rural Settings.

Rural populations continue to experience persistent cancer disparities compared with urban populations particularly in cancers that can be prevented or detected early through screening and vaccination. Although the National Cancer Institute and the larger cancer research community have identified rural community partnerships as the foundation for reducing the disparities, we have identified limited application of community-based participatory research in cancer prevention and control research. Guided by the Community-Based Participatory Research Conceptual Model and our collective experience, we provide a framework for a community-cancer center partnership that focuses on promoting health equity. In this commentary, we articulate that the partnership process must foster capacity for communities and cancer centers, strive for rural representation in clinical trials and biobanking, build a pipeline for dissemination and implementation research, and create a bidirectional flow of knowledge between communities and academic institutions. Authentic partnerships with rural communities should be the ultimate goal of cancer centers, and the process described in this commentary can serve as an initial platform to build capacity and continue to strive toward that goal.

Breast Cancer Screening Strategies for Women With ATM, CHEK2, and PALB2 Pathogenic Variants: A Comparative Modeling Analysis.

IMPORTANCE: Screening mammography and magnetic resonance imaging (MRI) are recommended for women with ATM, CHEK2, and PALB2 pathogenic variants. However, there are few data to guide screening regimens for these women. OBJECTIVE: To estimate the benefits and harms of breast cancer screening strategies using mammography and MRI at various start ages for women with ATM, CHEK2, and PALB2 pathogenic variants. DESIGN, SETTING, AND PARTICIPANTS: This comparative modeling analysis used 2 established breast cancer microsimulation models from the Cancer Intervention and Surveillance Modeling Network (CISNET) to evaluate different screening strategies. Age-specific breast cancer risks were estimated using aggregated data from the Cancer Risk Estimates Related to Susceptibility (CARRIERS) Consortium for 32 247 cases and 32 544 controls in 12 population-based studies. Data on screening performance for mammography and MRI were estimated from published literature. The models simulated US women with ATM, CHEK2, or PALB2 pathogenic variants born in 1985. INTERVENTIONS: Screening strategies with combinations of annual mammography alone and with MRI starting at age 25, 30, 35, or 40 years until age 74 years. MAIN OUTCOMES AND MEASURES: Estimated lifetime breast cancer mortality reduction, life-years gained, breast cancer deaths averted, total screening examinations, false-positive screenings, and benign biopsies per 1000 women screened. Results are reported as model mean values and ranges. RESULTS: The mean model-estimated lifetime breast cancer risk was 20.9% (18.1%-23.7%) for women with ATM pathogenic variants, 27.6% (23.4%-31.7%) for women with CHEK2 pathogenic variants, and 39.5% (35.6%-43.3%) for women with PALB2 pathogenic variants. Across pathogenic variants, annual mammography alone from 40 to 74 years was estimated to reduce breast cancer mortality by 36.4% (34.6%-38.2%) to 38.5% (37.8%-39.2%) compared with no screening. Screening with annual MRI starting at 35 years followed by annual mammography and MRI at 40 years was estimated to reduce breast cancer mortality by 54.4% (54.2%-54.7%) to 57.6% (57.2%-58.0%), with 4661 (4635-4688) to 5001 (4979-5023) false-positive screenings and 1280 (1272-1287) to 1368 (1362-1374) benign biopsies per 1000 women. Annual MRI starting at 30 years followed by mammography and MRI at 40 years was estimated to reduce mortality by 55.4% (55.3%-55.4%) to 59.5% (58.5%-60.4%), with 5075 (5057-5093) to 5415 (5393-5437) false-positive screenings and 1439 (1429-1449) to 1528 (1517-1538) benign biopsies per 1000 women. When starting MRI at 30 years, initiating annual mammography starting at 30 vs 40 years did not meaningfully reduce mean mortality rates (0.1% [0.1%-0.2%] to 0.3% [0.2%-0.3%]) but was estimated to add 649 (602-695) to 650 (603-696) false-positive screenings and 58 (41-76) to 59 (41-76) benign biopsies per 1000 women. CONCLUSIONS AND RELEVANCE: This analysis suggests that annual MRI screening starting at 30 to 35 years followed by annual MRI and mammography at 40 years may reduce breast cancer mortality by more than 50% for women with ATM, CHEK2, and PALB2 pathogenic variants. In the setting of MRI screening, mammography prior to 40 years may offer little additional benefit.

Coordinating Centers as a Strategy for Accelerating Cancer Epidemiology Consortia: Best Practices.

Purposeof Review: This review highlights six "best practices" for cancer epidemiology coordinating centers to facilitate the success of a research consortium. Recent Findings: Evidence from emerging literature regarding the Science of Team Science suggests that coordinating centers can more effectively foster collaborative cancer epidemiology research in consortia by (1) establishing collaboration as a shared goal at the start, (2) providing scientific expertise complementary to the research sites that adapts over the course of the project, (3) enacting anti-racist and inclusive approaches in all consortium decisions and activities, (4) fostering early-stage investigator career development, (5) engaging stakeholders including cancer survivors as peers, and (6) delivering reliable logistical support and technology tools with planned process evaluation so that researchers can collaboratively focus on the science. Summary: By drawing on the Science of Team Science, coordinating centers can accelerate research progress and increase the impact of cancer epidemiology consortia.

Mortality risk and physical activity across the lifespan in endometrial cancer survivors.

PURPOSE: Physical activity (pre- and post-diagnosis) has been studied in prevention and survivorship contexts for endometrial cancer. However, the association of physical activity (PA) across the lifespan on mortality risk among endometrial cancer survivors is understudied. The study's objective was to identify the association of lifetime PA on mortality risk in endometrial cancer survivors. METHODS: Seven hundred forty-five endometrial cancer survivors drawn from a population-based cancer registry (diagnosed between 1991 and 1994) reported the frequency (sessions/week) of moderate- and vigorous intensity physical activity (MVPA) at age 12, age 20, and 5 years pre-interview (post-diagnosis). Cox proportional hazards were used to estimate hazard ratios (HR) and 95% confidence intervals for the association between PA, all-cause, and cardiovascular disease mortality as assessed in 2016. MVPA was modeled using natural cubic splines. RESULTS: Diagnosis age, body mass index, and smoking (pack-years) were each positively associated with increased all-cause mortality risk. Those who did one session of MVPA 5 years pre-interview had a lower mortality risk (HR 0.61; 95% CI 0.41-0.92) compared to those with no MVPA. Those reporting one session of MVPA was similarly observed at age 12 (HR 0.95; 95% CI 0.86-1.06) and at age 20 (HR 0.87; 95% CI 0.65-1.16). CONCLUSION: Those who participated in PA, compared to those who did not, in the 5 years before diagnosis had a lower mortality risk. While PA was not independently protective against mortality risk at ages 12 or 20, PA is still important for endometrial cancer survivors for other non-mortality outcomes.

Breast Cancer Screening Among Childhood Cancer Survivors Treated Without Chest Radiation: Clinical Benefits and Cost-Effectiveness.

BACKGROUND: Early initiation of breast cancer screening is recommended for high-risk women, including survivors of childhood cancer treated with chest radiation. Recent studies suggest that female survivors of childhood leukemia or sarcoma treated without chest radiation are also at elevated early onset breast cancer risk. However, the potential clinical benefits and cost-effectiveness of early breast cancer screening among these women are uncertain. METHODS: Using data from the Childhood Cancer Survivor Study, we adapted 2 Cancer Intervention and Surveillance Modeling Network simulation models to reflect the elevated risks of breast cancer and competing mortality among leukemia and sarcoma survivors. Costs and utility weights were based on published studies and databases. Outcomes included breast cancer deaths averted, false-positive screening results, benign biopsies, and incremental cost-effectiveness ratios. RESULTS: In the absence of screening, the lifetime risk of dying from breast cancer among survivors was 6.8% to 7.0% across models. Early initiation of annual mammography with breast magnetic resonance imaging screening between ages 25 and 40 years would avert 52.6% to 64.3% of breast cancer deaths. When costs and quality-of-life impacts were considered, screening starting at age 40 years was the only strategy with an incremental cost-effectiveness ratio below the $100 000 per quality-adjusted life-year (QALY) gained cost-effectiveness threshold ($27 680 to $44 380 per QALY gained across models). CONCLUSIONS: Among survivors of childhood leukemia or sarcoma, early initiation of breast cancer screening at age 40 years may reduce breast cancer deaths by half and is cost-effective. These findings could help inform screening guidelines for survivors treated without chest radiation.