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Background: Identifying risk factors for breast cancer specific to women in their 40s could inform screening decisions.Purpose: To determine what factors increase risk for breast cancer in women aged 40 to 49 years and the magnitude of risk for each factor.Data Sources: MEDLINE (January 1996 to the second week of November 2011), Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews (fourth quarter of 2011), Scopus, reference lists of published studies, and the Breast Cancer Surveillance Consortium.Study Selection: English-language studies and systematic reviews of risk factors for breast cancer in women aged 40 to 49 years. Additional inclusion criteria were applied for each risk factor.Data Extraction: Data on participants, study design, analysis, follow-up, and outcomes were abstracted. Study quality was rated by using established criteria, and only studies rated as good or fair were included. Results were summarized by using meta-analysis when sufficient studies were available or from the best evidence based on study quality, size, and applicability when meta-analysis was not possible. Data from the Breast Cancer Surveillance Consortium were analyzed with proportional hazards models by using partly conditional Cox regression. Reference groups for comparisons were set at U.S. population means.Data Synthesis: Sixty-six studies provided data for estimates. Extremely dense breasts on mammography or first-degree relatives with breast cancer were associated with at least a 2-fold increase in risk for breast cancer. Prior breast biopsy, second-degree relatives with breast cancer, or heterogeneously dense breasts were associated with a 1.5- to 2.0-fold increased risk; current use of oral contraceptives, nulliparity, and age 30 years or older at first birth were associated with a 1.0- to 1.5-fold increased risk.Limitations: Studies varied by measures, reference groups, and adjustment for confounders, which could bias combined estimates. Effects of multiple risk factors were not considered.Conclusion: Extremely dense breasts and first-degree relatives with breast cancer were each associated with at least a 2-fold increase in risk for breast cancer in women aged 40 to 49 years. Identification of these risk factors may be useful for personalized mammography screening.Primary Funding Source: National Cancer Institute. [ABSTRACT FROM AUTHOR]

Although caffeine can enhance cognitive function acutely, long-term effects of consumption of caffeine-containing beverages such as tea and coffee are uncertain. Data on 4,809 participants aged 65 and older from the Cardiovascular Health Study (CHS) were used to examine the relationship of consumption of tea and coffee, assessed by food frequency questionnaire, on change in cognitive function by gender. Cognitive performance was assessed using serial Modified Mini-Mental State (3MS) examinations, which were administered annually up to 9 times. Linear mixed models were used to estimate rates of change in standard 3MS scores and scores modeled using item response theory (IRT). Models were adjusted for age, education, smoking status, clinic site, diabetes, hypertension, stroke, coronary heart disease, depression score, and APOE genotype. Over the median 7.9 years of follow-up, participants who did not consume tea or coffee declined annually an average of 1.30 points (women) and 1.11 points (men) on standard 3MS scores. In fully adjusted models using either standard or IRT 3MS scores, we found modestly reduced rates of cognitive decline for some, but not all, levels of coffee and tea consumption for women, with no consistent effect for men. Caffeine consumption was also associated with attenuation in cognitive decline in women. Dose-response relationships were not linear. These longitudinal analyses suggest a somewhat attenuated rate of cognitive decline among tea and coffee consumers compared to non-consumers in women but not in men. Whether this association is causal or due to unmeasured confounding requires further study. [ABSTRACT FROM AUTHOR]

The authors used data from the Multi-Ethnic Study of Atherosclerosis and latent trajectory class modeling to determine patterns of neighborhood poverty over 20 years (1980-2000 residential history questionnaires were geocoded and linked to US Census data). Using these patterns, the authors examined 1) whether trajectories of neighborhood poverty were associated with differences in the amount of subclinical atherosclerosis (common carotid intimal-media thickness) and 2) associated risk factors (body mass index, hypertension, diabetes, current smoking) at baseline (January 2000-August 2002). The authors found evidence of 5 stable trajectory groups with differing levels of neighborhood poverty ( approximately 6%, 12%, 20%, 30%, and 45%) and 1 group with 29% poverty in 1980 and approximately 11% in 2000. Mostly for women, higher cumulative neighborhood poverty was generally significantly associated with worse cardiovascular outcomes. Trends generally persisted after adjustment for adulthood socioeconomic position and race/ethnicity, although they were no longer statistically significant. Among women who had moved during the 20 years, the long-term measure had stronger associations with outcomes (except smoking) than a single, contemporaneous measure. Results indicate that cumulative 20-year exposure to neighborhood poverty is associated with greater cardiovascular risk for women. In residentially mobile populations, single-point-in-time measures underestimate long-term effects. [ABSTRACT FROM AUTHOR]

Context: The herbal product Ginkgo biloba is taken frequently with the intention of improving cognitive health in aging. However, evidence from adequately powered clinical trials is lacking regarding its effect on long-term cognitive functioning.Objective: To determine whether G. biloba slows the rates of global or domain-specific cognitive decline in older adults.Design, Setting, and Participants: The Ginkgo Evaluation of Memory (GEM) study, a randomized, double-blind, placebo-controlled clinical trial of 3069 community-dwelling participants aged 72 to 96 years, conducted in 6 academic medical centers in the United States between 2000 and 2008, with a median follow-up of 6.1 years.Intervention: Twice-daily dose of 120-mg extract of G. biloba (n = 1545) or identical-appearing placebo (n = 1524).Main Outcome Measures: Rates of change over time in the Modified Mini-Mental State Examination (3MSE), in the cognitive subscale of the Alzheimer Disease Assessment Scale (ADAS-Cog), and in neuropsychological domains of memory, attention, visual-spatial construction, language, and executive functions, based on sums of z scores of individual tests.Results: Annual rates of decline in z scores did not differ between G. biloba and placebo groups in any domains, including memory (0.043; 95% confidence interval [CI], 0.034-0.051 vs 0.041; 95% CI, 0.032-0.050), attention (0.043; 95% CI, 0.037-0.050 vs 0.048; 95% CI, 0.041-0.054), visuospatial abilities (0.107; 95% CI, 0.097-0.117 vs 0.118; 95% CI, 0.108-0.128), language (0.045; 95% CI, 0.037-0.054 vs 0.041; 95% CI, 0.033-0.048), and executive functions (0.092; 95% CI, 0.086-0.099 vs 0.089; 95% CI, 0.082-0.096). For the 3MSE and ADAS-Cog, rates of change varied by baseline cognitive status (mild cognitive impairment), but there were no differences in rates of change between treatment groups (for 3MSE, P = .71; for ADAS-Cog, P = .97). There was no significant effect modification of treatment on rate of decline by age, sex, race, education, APOE*E4 allele, or baseline mild cognitive impairment (P > .05).Conclusion: Compared with placebo, the use of G. biloba, 120 mg twice daily, did not result in less cognitive decline in older adults with normal cognition or with mild cognitive impairment.Trial Registration: clinicaltrials.gov Identifier: NCT00010803. [ABSTRACT FROM AUTHOR]

Little is known about environmental determinants of type 2 diabetes. The authors hypothesized that insulin resistance is positively related to distance to a wealthy area and to local neighborhood poverty. Data were derived from The Multi-Ethnic Study of Atherosclerosis, a study of adults aged 45-84 years in six US locales, and the 2000 US Census. The homeostasis model assessment (HOMA) index was used to measure insulin resistance. Linear regression was used to estimate associations between area characteristics and insulin resistance after adjustment for age, sex, income, education, and race/ethnicity and for the potential mediators diet, physical activity, and body mass index (n = 4,821). Among persons not treated for diabetes, distance to a wealthy area was associated with HOMA independent of local poverty and person-level covariates: per 4.4-km change, the relative increase in HOMA was 13% (95% confidence interval: 7%, 19%), similar to the effect of a body mass index increase of 1.7 kg/m(2) on HOMA. This association was reduced after adjustment for physical activity, diet, and body mass index (relative increase = 9%, 95% confidence interval: 3%, 15%). Local neighborhood poverty was also positively, but more weakly associated with insulin resistance, with no association after adjustment for race/ethnicity. This study shows that proximity to resources in high-income areas is related to insulin resistance. [ABSTRACT FROM AUTHOR]

Breast density is associated with risk of breast cancer (BC) diagnosis, impacting risk prediction tools and patient notification policies. Density affects mammography sensitivity and may influence screening intensity. Therefore, the observed association between density and BC diagnosis may not reflect the relationship between density and disease risk. We investigate the association between breast density and BC risk using data sourced from 33,542 women in the Breast Cancer Surveillance Consortium, 2000-2018. We estimated mammogram sensitivity and rates of screening mammography among dense (BI-RADS c, d) and non-dense (BI-RADS a, b) breasts. We used Kaplan-Meier estimates to summarize the relative risks of BC diagnosis (RRdx) by density and fit a natural history model to estimate the relative risks of BC onset (RRonset) given density-specific sensitivities. RRdx for dense versus non-dense breasts was 1.80 (95% CI 1.46 to 2.57). Based on estimated screening sensitivities of 0.88 and .78 for non-dense and dense breasts, respectively, RRonset was 1.73 (95% CI 1.43 to 2.25). Sensitivity analyses suggested higher breast density is robustly associated with increased risk of BC onset, similar in magnitude to the increased risk of BC diagnosis. These finding support laws requiring notifications to women with dense breasts of their increased BC risk., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background It is unclear whether breast US screening outcomes for women with dense breasts vary with levels of breast cancer risk. Purpose To evaluate US screening outcomes for female patients with dense breasts and different estimated breast cancer risk levels. Materials and Methods This retrospective observational study used data from US screening examinations in female patients with heterogeneously or extremely dense breasts conducted from January 2014 to October 2020 at 24 radiology facilities within three Breast Cancer Surveillance Consortium (BCSC) registries. The primary outcomes were the cancer detection rate, false-positive biopsy recommendation rate, and positive predictive value of biopsies performed (PPV3). Risk classification of participants was performed using established BCSC risk prediction models of estimated 6-year advanced breast cancer risk and 5-year invasive breast cancer risk. Differences in high- versus low- or average-risk categories were assessed using a generalized linear model. Results In total, 34 791 US screening examinations from 26 489 female patients (mean age at screening, 53.9 years ± 9.0 [SD]) were included. The overall cancer detection rate per 1000 examinations was 2.0 (95% CI: 1.6, 2.4) and was higher in patients with high versus low or average risk of 6-year advanced breast cancer (5.5 [95% CI: 3.5, 8.6] vs 1.3 [95% CI: 1.0, 1.8], respectively; P = .003). The overall false-positive biopsy recommendation rate per 1000 examinations was 29.6 (95% CI: 22.6, 38.6) and was higher in patients with high versus low or average 6-year advanced breast cancer risk (37.0 [95% CI: 28.2, 48.4] vs 28.1 [95% CI: 20.9, 37.8], respectively; P = .04). The overall PPV3 was 6.9% (67 of 975; 95% CI: 5.3, 8.9) and was higher in patients with high versus low or average 6-year advanced cancer risk (15.0% [15 of 100; 95% CI: 9.9, 22.2] vs 4.9% [30 of 615; 95% CI: 3.3, 7.2]; P = .01). Similar patterns in outcomes were observed by 5-year invasive breast cancer risk. Conclusion The cancer detection rate and PPV3 of supplemental US screening increased with the estimated risk of advanced and invasive breast cancer. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Helbich and Kapetas in this issue.

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.

Background: Examining screening outcomes by breast density for breast magnetic resonance imaging (MRI) with or without mammography could inform discussions about supplemental MRI in women with dense breasts., Methods: We evaluated 52 237 women aged 40-79 years who underwent 2611 screening MRIs alone and 6518 supplemental MRI plus mammography pairs propensity score-matched to 65 810 screening mammograms. Rates per 1000 examinations of interval, advanced, and screen-detected early stage invasive cancers and false-positive recall and biopsy recommendation were estimated by breast density (nondense = almost entirely fatty or scattered fibroglandular densities; dense = heterogeneously/extremely dense) adjusting for registry, examination year, age, race and ethnicity, family history of breast cancer, and prior breast biopsy., Results: Screen-detected early stage cancer rates were statistically higher for MRI plus mammography vs mammography for nondense (9.3 vs 2.9; difference = 6.4, 95% confidence interval [CI] = 2.5 to 10.3) and dense (7.5 vs 3.5; difference = 4.0, 95% CI = 1.4 to 6.7) breasts and for MRI vs MRI plus mammography for dense breasts (19.2 vs 7.5; difference = 11.7, 95% CI = 4.6 to 18.8). Interval rates were not statistically different for MRI plus mammography vs mammography for nondense (0.8 vs 0.5; difference = 0.4, 95% CI = -0.8 to 1.6) or dense breasts (1.5 vs 1.4; difference = 0.0, 95% CI = -1.2 to 1.3), nor were advanced cancer rates. Interval rates were not statistically different for MRI vs MRI plus mammography for nondense (2.6 vs 0.8; difference = 1.8 (95% CI = -2.0 to 5.5) or dense breasts (0.6 vs 1.5; difference = -0.9, 95% CI = -2.5 to 0.7), nor were advanced cancer rates. False-positive recall and biopsy recommendation rates were statistically higher for MRI groups than mammography alone., Conclusion: MRI screening with or without mammography increased rates of screen-detected early stage cancer and false-positives for women with dense breasts without a concomitant decrease in advanced or interval cancers., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Guidelines recommend shared decision-making (SDM) around mammography screening for women ≥ 75 years old., Objective: To use microsimulation modeling to estimate the lifetime benefits and harms of screening women aged 75, 80, and 85 years based on their individual risk factors (family history, breast density, prior biopsy) and comorbidity level to support SDM in clinical practice., Design, Setting, and Participants: We adapted two established Cancer Intervention and Surveillance Modeling Network (CISNET) models to evaluate the remaining lifetime benefits and harms of screening U.S. women born in 1940, at decision ages 75, 80, and 85 years considering their individual risk factors and comorbidity levels. Results were summarized for average- and higher-risk women (defined as having breast cancer family history, heterogeneously dense breasts, and no prior biopsy, 5% of the population)., Main Outcomes and Measures: Remaining lifetime breast cancers detected, deaths (breast cancer/other causes), false positives, and overdiagnoses for average- and higher-risk women by age and comorbidity level for screening (one or five screens) vs. no screening per 1000 women., Results: Compared to stopping, one additional screen at 75 years old resulted in six and eight more breast cancers detected (10% overdiagnoses), one and two fewer breast cancer deaths, and 52 and 59 false positives per 1000 average- and higher-risk women without comorbidities, respectively. Five additional screens over 10 years led to 23 and 31 additional breast cancer cases (29-31% overdiagnoses), four and 15 breast cancer deaths avoided, and 238 and 268 false positives per 1000 average- and higher-risk screened women without comorbidities, respectively. Screening women at older ages (80 and 85 years old) and high comorbidity levels led to fewer breast cancer deaths and a higher percentage of overdiagnoses., Conclusions: Simulation models show that continuing screening in women ≥ 75 years old results in fewer breast cancer deaths but more false positive tests and overdiagnoses. Together, clinicians and 75 + women may use model output to weigh the benefits and harms of continued screening., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Objectives: Cancer risk prediction may be subject to detection bias if utilization of screening is related to cancer risk factors. We examine detection bias when predicting breast cancer risk by race/ethnicity., Methods: We used screening and diagnosis histories from the Breast Cancer Surveillance Consortium to estimate risk of breast cancer onset and calculated relative risk of onset and diagnosis for each racial/ethnic group compared with non-Hispanic White women., Results: Of 104,073 women aged 40-54 receiving their first screening mammogram at a Breast Cancer Surveillance Consortium facility between 2000 and 2018, 10.2% (n = 10,634) identified as Asian, 10.9% (n = 11,292) as Hispanic, and 8.4% (n = 8719) as non-Hispanic Black. Hispanic and non-Hispanic Black women had slightly lower screening frequencies but biopsy rates following a positive mammogram were similar across groups. Risk of cancer diagnosis was similar for non-Hispanic Black and White women (relative risk vs non-Hispanic White = 0.90, 95% CI 0.65 to 1.14) but was lower for Asian (relative risk = 0.70, 95% CI 0.56 to 0.97) and Hispanic women (relative risk = 0.82, 95% CI 0.62 to 1.08). Relative risks of disease onset were 0.78 (95% CI 0.68 to 0.88), 0.70 (95% CI 0.59 to 0.83), and 0.95 (95% CI 0.84 to 1.09) for Asian, Hispanic, and non-Hispanic Black women, respectively., Conclusions: Racial/ethnic differences in mammography and biopsy utilization did not induce substantial detection bias; relative risks of disease onset were similar to or modestly different than relative risks of diagnosis. Asian and Hispanic women have lower risks of developing breast cancer than non-Hispanic Black and White women, who have similar risks., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: DLM received an honorarium from Society for Breast Imaging for keynote lecture in April 2019 and receives royalties from Elsevier. CIL received a Research Grant from GE Healthcare and receives textbook royalties from McGraw-Hill, Oxford University Press, Wolters Kluwer and payments from the American College of Radiology for JACR Deputy Editor duties.

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., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

There are >1.9 million survivors of adolescent and young adult cancers (AYA, diagnosed at ages 15-39) living in the U.S. today. Epidemiologic studies to address the cancer burden in this group have been a relatively recent focus of the research community. In this article, we discuss approaches and data resources for cancer epidemiology and health services research in the AYA population. We consider research that uses data from cancer registries, vital records, healthcare utilization, and surveys, and the accompanying challenges and opportunities of each. To illustrate the strengths of each data source, we present example research questions or areas that are aligned with these data sources and salient to AYAs. Integrating the respective strengths of cancer registry, vital records, healthcare data, and survey-based studies sets the foundation for innovative and impactful research on AYA cancer treatment and survivorship to inform a comprehensive understanding of diverse AYA needs and experiences., Competing Interests: Conflicts of interest/Competing interests The authors declare there are no potential conflicts of interest.

Background: There are no consensus guidelines for supplemental breast cancer screening with whole-breast ultrasound. However, criteria for women at high risk of mammography screening failures (interval invasive cancer or advanced cancer) have been identified. Mammography screening failure risk was evaluated among women undergoing supplemental ultrasound screening in clinical practice compared with women undergoing mammography alone., Methods: A total of 38,166 screening ultrasounds and 825,360 screening mammograms without supplemental screening were identified during 2014-2020 within three Breast Cancer Surveillance Consortium (BCSC) registries. Risk of interval invasive cancer and advanced cancer were determined using BCSC prediction models. High interval invasive breast cancer risk was defined as heterogeneously dense breasts and BCSC 5-year breast cancer risk ≥2.5% or extremely dense breasts and BCSC 5-year breast cancer risk ≥1.67%. Intermediate/high advanced cancer risk was defined as BCSC 6-year advanced breast cancer risk ≥0.38%., Results: A total of 95.3% of 38,166 ultrasounds were among women with heterogeneously or extremely dense breasts, compared with 41.8% of 825,360 screening mammograms without supplemental screening (p < .0001). Among women with dense breasts, high interval invasive breast cancer risk was prevalent in 23.7% of screening ultrasounds compared with 18.5% of screening mammograms without supplemental imaging (adjusted odds ratio, 1.35; 95% CI, 1.30-1.39); intermediate/high advanced cancer risk was prevalent in 32.0% of screening ultrasounds versus 30.5% of screening mammograms without supplemental screening (adjusted odds ratio, 0.91; 95% CI, 0.89-0.94)., Conclusions: Ultrasound screening was highly targeted to women with dense breasts, but only a modest proportion were at high mammography screening failure risk. A clinically significant proportion of women undergoing mammography screening alone were at high mammography screening failure risk., (© 2023 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Importance: Digital breast tomosynthesis (DBT) was developed with the expectation of improving cancer detection in women with dense breasts. Studies are needed to evaluate interval invasive and advanced breast cancer rates, intermediary outcomes related to breast cancer mortality, by breast density and breast cancer risk., Objective: To evaluate whether DBT screening is associated with a lower likelihood of interval invasive cancer and advanced breast cancer compared with digital mammography by extent of breast density and breast cancer risk., Design, Setting, and Participants: Cohort study of 504 427 women aged 40 to 79 years who underwent 1 003 900 screening digital mammography and 375 189 screening DBT examinations from 2011 through 2018 at 44 US Breast Cancer Surveillance Consortium (BCSC) facilities with follow-up for cancer diagnoses through 2019 by linkage to state or regional cancer registries., Exposures: Breast Imaging Reporting and Data System (BI-RADS) breast density; BCSC 5-year breast cancer risk., Main Outcomes and Measures: Rates per 1000 examinations of interval invasive cancer within 12 months of screening mammography and advanced breast cancer (prognostic pathologic stage II or higher) within 12 months of screening mammography, both estimated with inverse probability weighting., Results: Among 504 427 women in the study population, the median age at time of mammography was 58 years (IQR, 50-65 years). Interval invasive cancer rates per 1000 examinations were not significantly different for DBT vs digital mammography (overall, 0.57 vs 0.61, respectively; difference, -0.04; 95% CI, -0.14 to 0.06; P = .43) or among all the 836 250 examinations with BCSC 5-year risk less than 1.67% (low to average-risk) or all the 413 061 examinations with BCSC 5-year risk of 1.67% or higher (high risk) across breast density categories. Advanced cancer rates were not significantly different for DBT vs digital mammography among women at low to average risk or at high risk with almost entirely fatty, scattered fibroglandular densities, or heterogeneously dense breasts. Advanced cancer rates per 1000 examinations were significantly lower for DBT vs digital mammography for the 3.6% of women with extremely dense breasts and at high risk of breast cancer (13 291 examinations in the DBT group and 31 300 in the digital mammography group; 0.27 vs 0.80 per 1000 examinations; difference, -0.53; 95% CI, -0.97 to -0.10) but not for women at low to average risk (10 611 examinations in the DBT group and 37 796 in the digital mammography group; 0.54 vs 0.42 per 1000 examinations; difference, 0.12; 95% CI, -0.09 to 0.32)., Conclusions and Relevance: Screening with DBT vs digital mammography was not associated with a significant difference in risk of interval invasive cancer and was associated with a significantly lower risk of advanced breast cancer among the 3.6% of women with extremely dense breasts and at high risk of breast cancer. No significant difference was observed in the 96.4% of women with nondense breasts, heterogeneously dense breasts, or with extremely dense breasts not at high risk.

Background: Mammography screening can lead to overdiagnosis-that is, screen-detected breast cancer that would not have caused symptoms or signs in the remaining lifetime. There is no consensus about the frequency of breast cancer overdiagnosis., Objective: To estimate the rate of breast cancer overdiagnosis in contemporary mammography practice accounting for the detection of nonprogressive cancer., Design: Bayesian inference of the natural history of breast cancer using individual screening and diagnosis records, allowing for nonprogressive preclinical cancer. Combination of fitted natural history model with life-table data to predict the rate of overdiagnosis among screen-detected cancer under biennial screening., Setting: Breast Cancer Surveillance Consortium (BCSC) facilities., Participants: Women aged 50 to 74 years at first mammography screen between 2000 and 2018., Measurements: Screening mammograms and screen-detected or interval breast cancer., Results: The cohort included 35 986 women, 82 677 mammograms, and 718 breast cancer diagnoses. Among all preclinical cancer cases, 4.5% (95% uncertainty interval [UI], 0.1% to 14.8%) were estimated to be nonprogressive. In a program of biennial screening from age 50 to 74 years, 15.4% (UI, 9.4% to 26.5%) of screen-detected cancer cases were estimated to be overdiagnosed, with 6.1% (UI, 0.2% to 20.1%) due to detecting indolent preclinical cancer and 9.3% (UI, 5.5% to 13.5%) due to detecting progressive preclinical cancer in women who would have died of an unrelated cause before clinical diagnosis., Limitations: Exclusion of women with first mammography screen outside BCSC., Conclusion: On the basis of an authoritative U.S. population data set, the analysis projected that among biennially screened women aged 50 to 74 years, about 1 in 7 cases of screen-detected cancer is overdiagnosed. This information clarifies the risk for breast cancer overdiagnosis in contemporary screening practice and should facilitate shared and informed decision making about mammography screening., Primary Funding Source: National Cancer Institute.

Introduction: Limited evidence exists on the impact of age and comorbidity on biopsy rates and findings among older women., Materials and Methods: We used data from 170,657 women ages 66-94 enrolled in the United States Breast Cancer Surveillance Consortium (BCSC). We estimated one-year rates of biopsy by type (any, fine-needle aspiration (FNA), core or surgical) and yield of the most invasive biopsy finding (benign, ductal carcinoma in situ (DCIS) and invasive breast cancer) by age and comorbidity. Statistical significance was assessed using Wald statistics comparing coefficients estimated from logistic regression models adjusted for age, comorbidity, BCSC registry, and interaction between age and comorbidity., Results: Of 524,860 screening mammograms, 9830 biopsies were performed following 7930 exams (1.5%) within one year, specifically 5589 core biopsies (1.1%), 3422 (0.7%) surgical biopsies and 819 FNAs (0.2%). Biopsy rates per 1000 screens decreased with age (66-74:15.7, 95%CI:14.8-16.8), 75-84:14.5(13.5-15.6), 85-94:13.2(11.3,15.4), p trend  < 0.001) and increased with Charlson Comorbidity Score (CCS = 0:14.4 (13.5-15.3), CCS = 1:16.6 (15.2-18.1), CCS ≥2:19.0 (16.9-21.5), p trend  < 0.001).Biopsy rates increased with CCS at ages 66-74 and 75-84 but not 85-94. Core and surgical biopsy rates increased with CCS at ages 66-74 only. For each biopsy type, the yield of invasive breast cancer increased with age irrespective of comorbidity., Discussion: Women aged 66-84 with significant comorbidity in a breast cancer screening population had higher breast biopsy rates and similar rates of invasive breast cancer diagnosis than their counterparts with lower comorbidity. A considerable proportion of these diagnoses may represent overdiagnoses, given the high competing risk of death from non-breast-cancer causes among older women., Competing Interests: Declaration of Competing Interest Dr. Braithwaite reports grants from National Cancer Institute (NCI) during the conduct of the study. Dr. Lee reports grants from NCI during the conduct of the study. Dr. Lee also reports grants from GE Healthcare to his institution, research consulting fees from GRAIL, Inc., personal fees for editorial board work from American College of Radiology, and textbook royalties from McGraw Hill, Inc., Oxford University Press, and UpToDate, Inc.; all outside the submitted work. Ms. Abraham reports grants from NCI during the conduct of the study. Dr. Buist reports grants from NCI during the conduct of the study. Dr. Miglioretti reports grants from NIH/NCI during the conduct of the study. Dr. O'Meara reports grants from NIH/NCI, during the conduct of the study. Dr. Sprague reports grants from NIH during the conduct of the study., (Published by Elsevier Ltd.)

Prior studies of screening mammography patterns by functional status in older women show inconsistent results. We used Breast Cancer Surveillance Consortium-Medicare linked data (1999-2014) to investigate the association of functional limitations with adherence to screening mammography in 145,478 women aged 66-74 years. Functional limitation was represented by a claims-based function-related indicator (FRI) score which incorporated 16 items reflecting functional status. Baseline adherence was defined as mammography utilization 9-30 months after the index screening mammography. Longitudinal adherence was examined among women adherent at baseline and defined as time from the index mammography to end of the first 30-month gap in mammography. Multivariable logistic regression and Cox proportional hazards models were used to investigate baseline and longitudinal adherence, respectively. Subgroup analyses were conducted by age (66-70 vs. 71-74 years). Overall, 69.6% of participants had no substantial functional limitation (FRI score 0), 23.5% had some substantial limitations (FRI score 1), and 6.8% had serious limitations (FRI score ≥ 2). Mean age at baseline was 68.5 years (SD = 2.6), 85.3% of participants were white, and 77.1% were adherent to screening mammography at baseline. Women with a higher FRI score were more likely to be non-adherent at baseline (FRI ≥ 2 vs. 0: aOR = 1.13, 95% CI = 1.06, 1.20, p-trend < 0.01). Similarly, a higher FRI score was associated with longitudinal non-adherence (FRI ≥ 2 vs. 0: aHR = 1.16, 95% CI = 1.11, 1.22, p-trend < 0.01). Effect measures of FRI did not differ substantially by age categories. Older women with a higher burden of functional limitations are less likely to be adherent to screening mammography recommendations., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: The cost-effectiveness of screening mammography beyond age 75 years remains unclear., Objective: To estimate benefits, harms, and cost-effectiveness of extending mammography to age 80, 85, or 90 years according to comorbidity burden., Design: Markov microsimulation model., Data Sources: SEER (Surveillance, Epidemiology, and End Results) program and Breast Cancer Surveillance Consortium., Target Population: U.S. women aged 65 to 90 years in groups defined by Charlson comorbidity score (CCS)., Time Horizon: Lifetime., Perspective: National health payer., Intervention: Screening mammography to age 75, 80, 85, or 90 years., Outcome Measures: Breast cancer death, survival, and costs., Results of Base-Case Analysis: Extending biennial mammography from age 75 to 80 years averted 1.7, 1.4, and 1.0 breast cancer deaths and increased days of life gained by 5.8, 4.2, and 2.7 days per 1000 women for comorbidity scores of 0, 1, and 2, respectively. Annual mammography beyond age 75 years was not cost-effective, but extending biennial mammography to age 80 years was ($54 000, $65 000, and $85 000 per quality-adjusted life-year [QALY] gained for women with CCSs of 0, 1, and ≥2, respectively). Overdiagnosis cases were double the number of deaths averted from breast cancer., Results of Sensitivity Analysis: Costs per QALY gained were sensitive to changes in invasive cancer incidence and shift of breast cancer stage with screening mammography., Limitation: No randomized controlled trials of screening mammography beyond age 75 years are available to provide model parameter inputs., Conclusion: Although annual mammography is not cost-effective, biennial screening mammography to age 80 years is; however, the absolute number of deaths averted is small, especially for women with comorbidities. Women considering screening beyond age 75 years should weigh the potential harms of overdiagnosis versus the potential benefit of averting death from breast cancer., Primary Funding Source: National Cancer Institute and National Institutes of Health.

The COVID-19 pandemic disrupted breast cancer screening and diagnostic imaging in the United States. We sought to evaluate how medical facilities prioritized breast imaging services during periods of reduced capacity or upon re-opening after closures. In fall 2020, we surveyed 77 breast imaging facilities within the Breast Cancer Surveillance Consortium in the United States. The survey ascertained the pandemic's impact on clinical practices during March-September 2020. Nearly all facilities (97%) reported closing or operating at reduced capacity at some point during this period. All facilities were open by August 2020, though 14% were still operating at reduced capacity in September 2020. During periods of re-opening or reduced capacity, 93% of facilities reported prioritizing diagnostic breast imaging over breast cancer screening. For diagnostic imaging, facilities prioritized based on rescheduling canceled appointments (89%), specific indication for diagnostic imaging (89%), patient demand (84%), individual characteristics and risk factors (77%), and time since last imaging examination (72%). For screening mammography, facilities prioritized based on rescheduled cancelations (96%), patient demand (83%), individual characteristics and risk factors (73%), and time since last mammogram (71%). For biopsy services, more than 90% of facilities reported prioritization based on rescheduling of canceled exams, patient demand, patient characteristics and risk factors and level of suspicion on imaging. The observed patterns from this large and geographically diverse sample of facilities in the United States indicate that multiple factors were commonly used to prioritize breast imaging services during periods of reduced capacity., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Previous reports suggested risk of death and breast cancer varied by comorbidity and age in older women undergoing mammography. However, impacts of functional limitations remain unclear., Methods: We used data from 238,849 women in the Breast Cancer Surveillance Consortium-Medicare linked database (1999-2015) who had screening mammogram at ages 66-94 years. We estimated risk of breast cancer, breast cancer death, and non-breast cancer death by function-related indicator (FRI) which incorporated 16 claims-based items and was categorized as an ordinal variable (0, 1, and 2+). Fine and Gray proportional sub-distribution hazards models were applied with breast cancer and death treated as competing events. Risk estimates by FRI scores were adjusted by age and NCI comorbidity index separately and stratified by these factors., Results: Overall, 9,252 women were diagnosed with breast cancer, 406 died of breast cancer, and 41,640 died from non-breast cancer causes. The 10-year age-adjusted invasive breast cancer risk slightly decreased with FRI score [FRI = 0: 4.0%, 95% confidence interval (CI) = 3.8-4.1; FRI = 1: 3.9%, 95% CI = 3.7-4.2; FRI ≥ 2: 3.5%, 95% CI = 3.1-3.9). Risk of non-breast cancer death increased with FRI score (FRI = 0: 18.8%, 95% CI = 18.5-19.1; FRI = 1: 24.4%, 95% CI = 23.9-25.0; FRI ≥ 2: 39.8%, 95% CI = 38.8-40.9]. Risk of breast cancer death was low with minimal differences across FRI scores. NCI comorbidity index-adjusted models and stratified analyses yielded similar patterns., Conclusions: Risk of non-breast cancer death substantially increases with FRI score, whereas risk of breast cancer death is low regardless of functional status., Impact: Older women with functional limitations should be informed that they may not benefit from screening mammography., (©2021 American Association for Cancer Research.)

Importance: Breast cancer screening, surveillance, and diagnostic imaging services were profoundly limited during the initial phase of the coronavirus disease 2019 (COVID-19) pandemic., Objective: To develop a risk-based strategy for triaging mammograms during periods of decreased capacity., Design, Setting, and Participants: This population-based cohort study used data collected prospectively from mammography examinations performed in 2014 to 2019 at 92 radiology facilities in the Breast Cancer Surveillance Consortium. Participants included individuals undergoing mammography. Data were analyzed from August 10 to November 3, 2020., Exposures: Clinical indication for screening, breast symptoms, personal history of breast cancer, age, time since last mammogram/screening interval, family history of breast cancer, breast density, and history of high-risk breast lesion., Main Outcomes and Measures: Combinations of clinical indication, clinical history, and breast cancer risk factors that subdivided mammograms into risk groups according to their cancer detection rate were identified using classification and regression trees., Results: The cohort included 898 415 individuals contributing 1 878 924 mammograms (mean [SD] age at mammogram, 58.6 [11.2] years) interpreted by 448 radiologists, with 1 722 820 mammograms in individuals without a personal history of breast cancer and 156 104 mammograms in individuals with a history of breast cancer. Most individuals were aged 50 to 69 years at imaging (1 113 174 mammograms [59.2%]), and 204 305 (11.2%) were Black, 206 087 (11.3%) were Asian or Pacific Islander, 126 677 (7.0%) were Hispanic or Latina, and 40 021 (2.2%) were another race/ethnicity or mixed race/ethnicity. Cancer detection rates varied widely based on clinical indication, breast symptoms, personal history of breast cancer, and age. The 12% of mammograms with very high (89.6 [95% CI, 82.3-97.5] to 122.3 [95% CI, 108.1-138.0] cancers detected per 1000 mammograms) or high (36.1 [95% CI, 33.1-39.3] to 47.5 [95% CI, 42.4-53.3] cancers detected per 1000 mammograms) cancer detection rates accounted for 55% of all detected cancers and included mammograms to evaluate an abnormal mammogram or breast lump in individuals of all ages regardless of breast cancer history, to evaluate breast symptoms other than lump in individuals with a breast cancer history or without a history but aged 60 years or older, and for short-interval follow-up in individuals aged 60 years or older without a breast cancer history. The 44.2% of mammograms with very low cancer detection rates accounted for 13.1% of detected cancers and included annual screening mammograms in individuals aged 50 to 69 years (3.8 [95% CI, 3.5-4.1] cancers detected per 1000 mammograms) and all screening mammograms in individuals younger than 50 years regardless of screening interval (2.8 [95% CI, 2.6-3.1] cancers detected per 1000 mammograms)., Conclusions and Relevance: In this population-based cohort study, clinical indication and individual risk factors were associated with cancer detection and may be useful for prioritizing mammography in times and settings of decreased capacity.

Introduction: Cardiovascular disease risk calculators can inform and guide preventive strategies and treatment decisions by clinicians and patients. However, their uptake in primary care has been slow despite the recommendation in national cardiovascular disease prevention guidelines. Identifying the barriers to the implementation of cardiovascular disease risk calculators is essential for promoting their adoption., Methods: The authors qualitatively analyzed structured physician educator notes written during an outreach education intervention with 44 small- and medium-sized primary care clinics that participated in the Agency for Healthcare Research and Quality‒funded EvidenceNOW Healthy Hearts Northwest trial. The authors coded barriers to the implementation of cardiovascular disease risk calculation and aligned them to the Consolidated Framework for Implementation Research., Results: The authors identified 13 barriers from the physician educators' notes. The majority (n=8, 62%) mapped to the framework's Inner Setting domain. The 5 most commonly noted barriers were (1) time constraints to use a calculator (N=23 clinics), (2) limitations to accessing a calculator or the necessary information to use a calculator (N=22 clinics), (3) no or minimal buy-in from clinicians or staff to use a calculator (N=19 clinics), (4) reported patient fear of side effects from statin medications or patient dislike of taking medications per the guidelines (N=17 clinics), and (5) lack of documented clinic workflow for using a calculator (N=16 clinics)., Conclusions: To improve the uptake of cardiovascular disease risk calculation in primary care, future cardiovascular disease prevention and implementation research should consider tailoring interventions to the common barriers to implementing cardiovascular disease risk calculation., Trial Registration: This study is registered at www.clinicaltrials.gov NCT02839382., (Copyright © 2020 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)

Importance: Digital breast tomosynthesis (DBT) has reduced recall and increased cancer detection compared with digital mammography (DM), depending on women's age and breast density. Whether DBT screening access and use are equitable across groups of women based on race/ethnicity and socioeconomic characteristics is uncertain., Objective: To determine women's access to and use of DBT screening based on race/ethnicity, educational attainment, and income., Design, Setting, and Participants: This cross-sectional study included 92 geographically diverse imaging facilities across 5 US states, at which a total of 2 313 118 screening examinations were performed among women aged 40 to 89 years from January 1, 2011, to December 31, 2017. Data were analyzed from June 13, 2019, to August 18, 2020., Exposures: Women's race/ethnicity, educational level, and community-level household income., Main Outcomes and Measures: Access to DBT (on-site access) at time of screening by examination year and actual use of DBT vs DM screening by years since facility-level DBT adoption (≤5 years)., Results: Among the 2 313 118 screening examinations included in the analysis, the proportion of women who had DBT access at the time of their screening appointment increased from 11 558 of 354 107 (3.3%) in 2011 to 194 842 of 235 972 (82.6%) in 2017. In 2012, compared with White women, Black (relative risk [RR], 0.05; 95% CI, 0.03-0.11), Asian American (RR, 0.28; 95% CI, 0.11-0.75), and Hispanic (RR, 0.38; 95% CI, 0.18-0.80) women had significantly less DBT access, and women with less than a high school education had lower DBT access compared with college graduates (RR, 0.18; 95% CI, 0.10-0.32). Among women attending facilities with both DM and DBT available at the time of screening, Black women experienced lower DBT use compared with White women attending the same facility (RRs, 0.83 [95% CI, 0.82-0.85] to 0.98 [95% CI, 0.97-0.99]); women with lower educational level experienced lower DBT use (RRs, 0.79 [95% CI, 0.74-0.84] to 0.88 [95% CI, 0.85-0.91] for non-high school graduates and 0.90 [95% CI, 0.89-0.92] to 0.96 [95% CI, 0.93-0.99] for high school graduates vs college graduates); and women within the lowest income quartile experienced lower DBT use vs women in the highest income quartile (RRs, 0.89 [95% CI, 0.87-0.91] to 0.99 [95% CI, 0.98-1.00]) regardless of the number of years after facility-level DBT adoption., Conclusions and Relevance: In this cross-sectional study, women of minority race/ethnicity and lower socioeconomic status experienced lower DBT access during the early adoption period and persistently lower DBT use when available over time. Future efforts should address racial/ethnic, educational, and financial barriers to DBT screening.

Background: Social determinants of health (SDOH) contribute to health care disparities, with social and economic barriers often leading to difficulties in obtaining necessary care. We evaluated barriers to receiving health care, focusing on caretaker responsibilities, health insurance and cost, and transportation. Materials and Methods: We included women ages ≥40 years receiving screening mammography across three Breast Cancer Surveillance Consortium registries from 2012 to 2017. Women self-reported social and financial barriers to receiving health care in the 12 months before their screening mammogram. We evaluated woman- and census-based community-level factors associated with reporting a barrier using multivariate logistic regression. We assessed interaction with urban versus nonurban residence using Wald tests. Results: Among 393,430 women, 3.6% reported a barrier with a higher proportion in urban versus nonurban settings (3.9% [ n  = 11,977] vs. 2.2% [ n  = 1,655], respectively; p  < 0.001). Among women reporting a barrier, health care cost and/or no insurance was the most common (49.3%), and no transportation was the least common (7.8%). Compared with white women, odds of reporting barriers were higher among black (adjusted odds ratio [aOR] = 1.30, 95% confidence interval [CI]: 1.16-1.44), Hispanic (aOR = 1.66, 95% CI: 1.53-1.80), and other race (aOR = 1.84, 95% CI: 1.65-2.04) women. Barriers were less likely in women with higher median household income (aOR = 0.69, 95% CI: 0.61-0.79) or higher average health insurance costs (aOR = 0.85, 95% CI: 0.74-0.98), but were more likely in high diversity index areas (aOR = 1.28, 95% CI: 1.11-1.48). Conclusions: Social and financial barriers exist based on race/ethnicity and SDOH related to income, insurance costs, and place of residence among women undergoing screening mammography. Breast imaging facilities could utilize information on these barriers to improve biennial screening adherence or ensure that women with abnormal findings obtain appropriate follow-up care through targeted interventions.

Background: Potential benefits of screening mammography among women ages 75 years and older remain unclear., Methods: We evaluated 10-year cumulative incidence of breast cancer and death from breast cancer and other causes by Charlson Comorbidity Index (CCI) and age in the Medicare-linked Breast Cancer Surveillance Consortium (1999-2010) cohort of 222 088 women with no less than 1 screening mammogram between ages 66 and 94 years., Results: During median follow-up of 107 months, 7583 were diagnosed with invasive breast cancer and 1742 with ductal carcinoma in situ; 471 died from breast cancer and 42 229 from other causes. The 10-year cumulative incidence of invasive breast cancer did not change with increasing CCI but decreased slightly with age: ages 66-74 years (CCI0 = 4.0% [95% CI = 3.9% to 4.2%] vs CCI  ≥ 2 = 3.9% [95% CI = 3.5% to 4.3%]); ages 75-84 years (CCI0 = 3.7% [95% CI = 3.5% to 3.9%] vs CCI  ≥ 2 = 3.4% [95% CI = 2.9% to 3.9%]); and ages 85-94 years (CCI0 = 2.7% [95% CI = 2.3% to 3.1%] vs CCI  ≥ 2 = 2.1% [95% CI = 1.3% to 3.0%]). The 10-year cumulative incidence of other-cause death increased with increasing CCI and age: ages 66-74 years (CCI0 = 10.4% [95% CI = 10.3 to 10.7%] vs CCI ≥ 2 = 43.4% [95% CI = 42.2% to 44.4%]), ages 75-84 years (CCI0 = 29.8% [95% CI = 29.3% to 30.2%] vs CCI ≥ 2 = 61.7% [95% CI = 60.2% to 63.3%]), and ages 85 to 94 years (CCI0 = 60.3% [95% CI = 59.1% to 61.5%] vs CCI  ≥ 2 = 84.8% [95% CI = 82.5% to 86.9%]). The 10-year cumulative incidence of breast cancer death was small and did not vary by age: ages 66-74 years = 0.2% (95% CI = 0.2% to 0.3%), ages 75-84 years = 0.29% (95% CI = 0.25% to 0.34%), and ages 85 to 94 years = 0.3% (95% CI = 0.2% to 0.4%)., Conclusions: Cumulative incidence of other-cause death was many times higher than breast cancer incidence and death, depending on comorbidity and age. Hence, older women with increased comorbidity may experience diminished benefit from continued screening., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Importance: Federal legislation proposes requiring that screening mammography reports to practitioners and women incorporate breast density information and that women with dense breasts discuss supplemental imaging with their practitioner given their increased risk of interval breast cancer. Instead of discussing supplemental imaging with all women with dense breasts, it may be more efficient to identify women at high risk of advanced breast cancer who may benefit most from supplemental imaging., Objective: To identify women at high risk of advanced breast cancer to target woman-practitioner discussions about the need for supplemental imaging., Design, Setting, and Participants: This prospective cohort study assessed 638 856 women aged 40 to 74 years who had 1 693 163 screening digital mammograms taken at Breast Cancer Surveillance Consortium (BCSC) imaging facilities from January 3, 2005, to December 31, 2014. Data analysis was performed from October 10, 2018, to March 20, 2019., Exposures: Breast Imaging Reporting and Data System (BI-RADS) breast density and BCSC 5-year breast cancer risk., Main Outcomes and Measures: Advanced breast cancer (stage IIB or higher) within 12 months of screening mammography; high advanced cancer rates (≥0.61 cases per 1000 mammograms) defined as the top 25th percentile of advanced cancer rates, and discussions per potential advanced cancer prevented., Results: A total of 638 856 women (mean [SD] age, 56.5 [8.9] years) were included in the study. Women with dense breasts (heterogeneously or extremely dense) accounted for 47.0% of screened women and 60.0% of advanced cancers. Low advanced cancer rates (<0.61 per 1000 mammograms) occurred in 34.5% of screened women with dense breasts. High advanced breast cancer rates occurred in women with heterogeneously dense breasts and a 5-year risk of 2.5% or higher (6.0% of screened women) and those with extremely dense breasts and a 5-year risk of 1.0% or higher (6.5% of screened women). Density-risk subgroups at high advanced cancer risk comprised 12.5% of screened women and 27.1% of advanced cancers. Density-risk subgroups had the fewest supplemental imaging discussions per potential advanced cancer prevented compared with a strategy based on dense breasts (1097 vs 1866 discussions). Women with heterogeneously dense breasts and a 5-year risk less than 1.67% (21.7% of screened women) had high rates of false-positive short-interval follow-up recommendation without undergoing supplemental imaging., Conclusions and Relevance: The findings suggest that breast density notification should be combined with breast cancer risk so women at highest risk for advanced cancer are targeted for supplemental imaging discussions and women at low risk are not. BI-RADS breast density combined with BCSC 5-year risk may offer a more efficient strategy for supplemental imaging discussions than targeting all women with dense breasts.

Purpose: We conducted a randomized controlled trial to compare the effectiveness of adding various forms of enhanced external support to practice facilitation on primary care practices' clinical quality measure (CQM) performance., Methods: Primary care practices across Washington, Oregon, and Idaho were eligible if they had fewer than 10 full-time clinicians. Practices were randomized to practice facilitation only, practice facilitation and shared learning, practice facilitation and educational outreach visits, or practice facilitation and both shared learning and educational outreach visits. All practices received up to 15 months of support. The primary outcome was the CQM for blood pressure control. Secondary outcomes were CQMs for appropriate aspirin therapy and smoking screening and cessation. Analyses followed an intention-to-treat approach., Results: Of 259 practices recruited, 209 agreed to be randomized. Only 42% of those offered educational outreach visits and 27% offered shared learning participated in these enhanced supports. CQM performance improved within each study arm for all 3 cardiovascular disease CQMs. After adjusting for differences between study arms, CQM improvements in the 3 enhanced practice support arms of the study did not differ significantly from those seen in practices that received practice facilitation alone (omnibus P = .40 for blood pressure CQM). Practices randomized to receive both educational outreach visits and shared learning, however, were more likely to achieve a blood pressure performance goal in 70% of patients compared with those randomized to practice facilitation alone (relative risk = 2.09; 95% CI, 1.16-3.76)., Conclusions: Although we found no significant differences in CQM performance across study arms, the ability of a practice to reach a target level of performance may be enhanced by adding both educational outreach visits and shared learning to practice facilitation., (© 2019 Annals of Family Medicine, Inc.)

Background: Breast density is strongly related to breast cancer. Identifying associations between environmental exposures and density may elucidate relationships with breast cancer. Metals and polycyclic aromatic hydrocarbons (PAHs) may influence breast density via oxidative stress or endocrine disruption., Methods: Study participants (n = 222,581) underwent a screening mammogram in 2011 at a radiology facility in the Breast Cancer Surveillance Consortium. Zip code residential levels of airborne PAHs and metals (arsenic, cadmium, chromium, cobalt, lead, manganese, mercury, nickel, and selenium) were assessed using the 2011 EPA National Air Toxics Assessment. Breast density was measured using the Breast Imaging-Reporting and Data System (BI-RADS) lexicon. Logistic regression was used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CI) for the individual air toxics and dense breasts (BI-RADS 3 or 4). Weighted quantile sum (WQS) regression was used to model the association between the air toxic mixture and density., Results: Higher residential levels of arsenic, cobalt, lead, manganese, nickel, or PAHs were individually associated with breast density. Comparing the highest to the lowest quartile, higher odds of having dense breasts were observed for cobalt (OR = 1.60, 95% CI 1.56-1.64) and lead (OR = 1.56, 95% CI 1.52-1.64). Associations were stronger for premenopausal women. The WQS index was associated with density overall (OR = 1.22, 95% CI 1.20-1.24); the most heavily weighted air toxics were lead and cobalt., Conclusions: In this first study to evaluate the association between air toxics and breast density, women living in areas with higher concentrations of lead and cobalt were more likely to have dense breasts.

Objective: The purpose of this study was to determine whether digital breast tomosynthesis (DBT) adoption was associated with a decrease in screening mammography capacity across Breast Cancer Screening Consortium facilities, given concerns about increasing imaging and interpretation times associated with DBT., Subjects and Methods: Facility characteristics and examination volume data were collected prospectively from Breast Cancer Screening Consortium facilities that adopted DBT between 2011 and 2014. Interrupted time series analyses using Poisson regression models in which facility was considered a random effect were used to evaluate differences between monthly screening volumes during the 12-month preadoption period and the 12-month postadoption period (with the two periods separated by a 3-month lag) and to test for changes in month-to-month facility-level screening volume during the preadoption and postadoption periods., Results: Across five regional breast imaging registries, 15 of 83 facilities (18.1%) adopted DBT for screening between 2011 and 2014. Most had no academic affiliation (73.3% [11/15]), were nonprofit (80.0% [12/15]), and were general radiology practices (66.7% [10/15]). Facility-level monthly screening volumes were slightly higher during the postadoption versus preadoption periods (relative risk [RR], 1.09; 95% CI, 1.06-1.11). Monthly screening volumes remained relatively stable within the preadoption period (RR, 1.00 per month; 95% CI 1.00-1.01 per month) and the postadoption period (RR, 1.00; 95% CI, 1.00-1.01 per month)., Conclusion: In a cohort of facilities with varied characteristics, monthly screening examination volumes did not decrease after DBT adoption.

Background: Disruption of insulin-like growth factor-I (IGF-I) increases health and life span in animal models, though this is unconfirmed in humans. If IGF-I stability indicates homeostasis, the absolute level of IGF-I may be less clinically relevant than maintaining an IGF-I setpoint., Methods: Participants were 945 U.S. community-dwelling individuals aged ≥65 years enrolled in the Cardiovascular Health Study with IGF-I levels at 3-6 timepoints. We examined the association of baseline IGF-I level, trajectory slope, and variability around the trajectory with mortality., Results: There were 633 deaths over median 11.3 years of follow-up. Lower IGF-I levels, declining or increasing slope, and increasing variability were each individually associated with higher mortality (all p < .001). In an adjusted model including all three trajectory parameters, baseline IGF-I levels <70 ng/mL (hazard ratio [HR] 1.58, 95% CI 1.28-1.96 relative to IGF-I levels of 170 ng/mL), steep declines and steep increases in trajectory slope (HR 2.22, 1.30-3.80 for a 15% decline; HR 1.40, 1.07-1.84 for a 10% decline; HR 1.80, 1.12-2.89 for a 15% increase; HR 1.31, 1.00-1.72 for a 10% increase, each vs no change), and variability ≥10% (HR 1.59, 1.09-2.32 for ≥ 30%; HR 1.36, 1.06-1.75 for 20%; and HR 1.17, 1.03-1.32 for 10% variability, each vs 0%) in IGF-I levels were independently associated with mortality., Conclusions: In contrast to data from animal models, low IGF-I levels are associated with higher mortality in older humans. Irrespective of the actual IGF-I level, older individuals with stability of IGF-I levels have lower mortality than those whose IGF-I levels fluctuate over time.

Background: Women at high lifetime breast cancer risk may benefit from supplemental breast magnetic resonance imaging (MRI) screening, in addition to routine mammography screening for earlier cancer detection., Materials and Methods: We performed a cross-sectional study of 422,406 women undergoing routine mammography screening across 86 Breast Cancer Surveillance Consortium (BCSC) facilities during calendar year 2012. We determined availability and use of on-site screening breast MRI services based on woman-level characteristics, including >20% lifetime absolute risk using the National Cancer Institute risk assessment tool. Multivariate analyses were performed to determine sociodemographic characteristics associated with on-site screening MRI use., Results: Overall, 43.9% (2403/5468) of women at high lifetime risk attended a facility with on-site breast MRI screening availability. However, only 6.6% (158/2403) of high-risk women obtained breast MRI screening within a 2-year window of their screening mammogram. Patient factors associated with on-site MRI screening use included younger (<40 years) age (odds ratio [OR] = 2.39, 95% confidence interval [CI]: 1.34-4.21), family history (OR = 1.72, 95% CI: 1.13-2.63), prior breast biopsy (OR = 2.09, 95% CI: 1.22-3.58), and postsecondary education (OR = 2.22, 95% CI: 1.04-4.74)., Conclusions: While nearly half of women at high lifetime breast cancer risk undergo routine screening mammography at a facility with on-site breast MRI availability, supplemental breast MRI remains widely underutilized among those who may benefit from earlier cancer detection. Future studies should evaluate whether other enabling factors such as formal risk assessment and patient awareness of high lifetime breast cancer risk can mitigate the underutilization of supplemental screening breast MRI.

Importance: There is little evidence on population-based harms and benefits of screening breast magnetic resonance imaging (MRI) in women with and without a personal history of breast cancer (PHBC)., Objective: To evaluate biopsy rates and yield in the 90 days following screening (mammography vs magnetic resonance imaging with or without mammography) among women with and without a PHBC., Design, Setting, and Participants: Observational cohort study of 6 Breast Cancer Surveillance Consortium (BCSC) registries. Population-based sample of 812 164 women undergoing screening, 2003 through 2013., Exposures: A total of 2 048 994 digital mammography and/or breast MRI screening episodes (mammogram alone vs MRI with or without screening mammogram within 30 days)., Main Outcomes and Measures: Biopsy intensity (surgical greater than core greater than fine-needle aspiration) and yield (invasive cancer greater than ductal carcinoma in situ greater than high-risk benign greater than benign) within 90 days of a screening episode. We computed age-adjusted rates of biopsy intensity (per 1000 screening episodes) and biopsy yield (per 1000 screening episodes with biopsies). Outcomes were stratified by PHBC and by BCSC 5-year breast cancer risk among women without PHBC., Results: We included 101 103 and 1 939 455 mammogram screening episodes in women with and without PHBC, respectively; MRI screening episodes included 3763 with PHBC and 4673 without PHBC. Age-adjusted core and surgical biopsy rates (per 1000 episodes) doubled (57.1; 95% CI, 50.3-65.1) following MRI compared with mammography (23.6; 95% CI, 22.4-24.8) in women with PHBC. Differences (per 1000 episodes) were even larger in women without PHBC: 84.7 (95% CI, 75.9-94.9) following MRI and 14.9 (95% CI, 14.7-15.0) following mammography episodes. Ductal carcinoma in situ and invasive biopsy yield (per 1000 episodes) was significantly higher following mammography compared with MRI episodes in women with PHBC (mammography, 404.6; 95% CI, 381.2-428.8; MRI, 267.6; 95% CI, 208.0-337.8) and nonsignificantly higher, but in the same direction, in women without PHBC (mammography, 279.3; 95% CI, 274.2-284.4; MRI, 214.6; 95% CI, 158.7-280.8). High-risk benign lesions were more commonly identified following MRI regardless of PHBC. Higher biopsy rates and lower cancer yield following MRI were not explained by increasing age or higher 5-year breast cancer risk., Conclusions and Relevance: Women with and without PHBC who undergo screening MRI experience higher biopsy rates coupled with significantly lower cancer yield findings following biopsy compared with screening mammography alone. Further work is needed to identify women who will benefit from screening MRI to ensure an acceptable benefit-to-harm ratio.

Background: Mammographic breast density is a well-established strong risk factor for breast cancer. The environmental contributors to geographic variation in breast density in urban and rural areas are poorly understood. We examined the association between breast density and exposure to ambient air pollutants (particulate matter <2.5 μm in diameter (PM 2.5 ) and ozone (O 3 )) in a large population-based screening registry., Methods: Participants included women undergoing mammography screening at imaging facilities within the Breast Cancer Surveillance Consortium (2001-2009). We included women aged ≥40 years with known residential zip codes before the index mammogram (n = 279,967). Breast density was assessed using the American College of Radiology's Breast Imaging-Reporting and Data System (BI-RADS) four-category breast density classification. PM 2.5 and O 3 estimates for grids across the USA (2001-2008) were obtained from the US Environmental Protection Agency Hierarchical Bayesian Model (HBM). For the majority of women (94%), these estimates were available for the year preceding the mammogram date. Association between exposure to air pollutants and density was estimated using polytomous logistic regression, adjusting for potential confounders., Results: Women with extremely dense breasts had higher mean PM 2.5 and lower O 3 exposures than women with fatty breasts (8.97 vs. 8.66 ug/m 3 and 33.70 vs. 35.82 parts per billion (ppb), respectively). In regression analysis, women with heterogeneously dense vs. scattered fibroglandular breasts were more likely to have higher exposure to PM 2.5 (fourth vs. first quartile odds ratio (OR) = 1.19, 95% confidence interval (CI) 1.16 - 1.23). Women with extremely dense vs. scattered fibroglandular breasts were less likely to have higher levels of ozone exposure (fourth vs. first quartile OR = 0.80, 95% CI 0.73-0.87)., Conclusion: Exposure to PM 2.5 and O 3 may in part explain geographical variation in mammographic density. Further studies are warranted to determine the causal nature of these associations.

Objective: Obesity is an important venous thrombosis (VT) risk factor but the reasons for this are unclear., Materials and Methods: In a cohort of 20,914 individuals aged 45 and older without prior VT, we calculated the relative risk (RR) of VT over 12.6years follow-up according to baseline body size measures, and studied whether associations were mediated by biomarkers of hemostasis and inflammation that are related to adiposity., Results: Greater levels of all body size measures (weight, height, waist, hip circumference, calf circumference, body-mass index, waist-hip ratio, fat mass and fat-free mass) were associated with increased risk of VT, with 4th versus 1st quartile RRs of 1.5-3.0. There were no multiplicative interactions of biomarkers with obesity status. Adjustment for biomarkers associated with VT risk and body size (factors VII and VIII, von Willebrand factor, partial thromboplastin time, D-dimer, C-reactive protein and factor XI) only marginally lowered, or did not impact, the RRs associated with body size measures., Conclusions: Greater body size, by multiple measures, is a risk factor for VT. Associations were not mediated by circulating levels of studied biomarkers suggesting that body size relates to VT because of physical factors associated with blood flow, not the hypercoagulability or inflammation associated with adiposity., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

In the U.S., guidelines recommend that women continue mammography screening until at least age 74, but recent evidence suggests declining screening rates in older women. We estimated adherence to screening mammography and multilevel factors associated with adherence in a longitudinal cohort of older women. Women aged 66-75years receiving screening mammography within the Breast Cancer Surveillance Consortium were linked to Medicare claims (2005-2010). Claims data identified baseline adherence, defined as receiving subsequent mammography within approximately 2years, and length of time adherent to guidelines. Characteristics associated with adherence were investigated using logistic and Cox proportional hazards regression models. Analyses were stratified by age to investigate variation in relationships between patient factors and adherence. Among 49,775 women, 89% were adherent at baseline. Among women 66-70years, those with less than a high school education were more likely to be non-adherent at baseline (odds ratio [OR] 1.96; 95% confidence interval [CI] 1.65-2.33) and remain adherent for less time (hazard ratio [HR] 1.41; 95% CI 1.11-1.80) compared to women with a college degree. Women with ≥1 versus no Charlson co-morbidities were more likely to be non-adherent at baseline (OR 1.46; 95% CI 1.31-1.62) and remain adherent for less time (HR 1.44; 95% CI 1.24-1.66). Women aged 71-75 had lower adherence overall, but factors associated with non-adherence were similar. In summary, adherence to guidelines is high among Medicare-enrolled women in the U.S. receiving screening mammography. Efforts are needed to ensure that vulnerable populations attain these same high levels of adherence., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Women screened with digital mammography may receive false-positive and false-negative results and subsequent imaging and biopsies. How these outcomes vary by age, time since the last screening, and individual risk factors is unclear., Objective: To determine factors associated with false-positive and false-negative digital mammography results, additional imaging, and biopsies among a general population of women screened for breast cancer., Design: Analysis of registry data., Setting: Participating facilities at 5 U.S. Breast Cancer Surveillance Consortium breast imaging registries with linkages to pathology databases and tumor registries., Patients: 405,191 women aged 40 to 89 years screened with digital mammography between 2003 and 2011. A total of 2963 were diagnosed with invasive cancer or ductal carcinoma in situ within 12 months of screening., Measurements: Rates of false-positive and false-negative results and recommendations for additional imaging and biopsies from a single screening round; comparisons by age, time since the last screening, and risk factors., Results: Rates of false-positive results (121.2 per 1000 women [95% CI, 105.6 to 138.7]) and recommendations for additional imaging (124.9 per 1000 women [CI, 109.3 to 142.3]) were highest among women aged 40 to 49 years and decreased with increasing age. Rates of false-negative results (1.0 to 1.5 per 1000 women) and recommendations for biopsy (15.6 to 17.5 per 1000 women) did not differ greatly by age. Results did not differ by time since the last screening. False-positive rates were higher for women with risk factors, particularly family history of breast cancer; previous benign breast biopsy result; high breast density; and, for younger women, low body mass index., Limitations: Confounding by variation in patient-level characteristics and outcomes across registries and regions may have been present. Some factors, such as numbers of first- and second-degree relatives with breast cancer and diagnoses associated with previous benign biopsy results, were not examined., Conclusion: False-positive mammography results and additional imaging are common, particularly for younger women and those with risk factors, whereas biopsies occur less often. Rates of false-negative results are low., Primary Funding Source: Agency for Healthcare Research and Quality and National Cancer Institute.

Delivery of screening mammography differs substantially between the United States (US) and Denmark. We evaluated whether there are differences in screening sensitivity and specificity. We included screens from women screened at age 50-69 years during 1996-2008/2009 in the US Breast Cancer Surveillance Consortium (BCSC) (n = 2,872,791), and from two population-based mammography screening programs in Denmark (Copenhagen, n = 148,156 and Funen, n = 275,553). Women were followed-up for 1 year. For initial screens, recall rate was significantly higher in BCSC (17.6%) than in Copenhagen (4.3%) and Funen (3.1%). Sensitivity was fairly similar in BCSC (91.8%) and Copenhagen (90.5%) and Funen (92.5%). At subsequent screens, recall rates were 8.8%, 1.8% and 1.4% in BCSC, Copenhagen and Funen, respectively. The BCSC sensitivity (82.3%) was lower compared with that in Copenhagen (88.9%) and Funen (86.9%), but when stratified by time since last screen, the sensitivity was similar. For both initial and subsequent screenings, the specificity of screening in BCSC (83.2% and 91.6%) was significantly lower than that in Copenhagen (96.6% and 98.8%) and Funen (97.9% and 99.2%). By taking time since last screen into account, it was found that American and Danish women had the same probability of having their asymptomatic cancers detected at screening. However, the majority of women free of asymptomatic cancers experienced more harms in terms of false-positive findings in the US than in Denmark., (© 2015 UICC.)

Introduction: In the United States (US), about one-half of women screened with annual mammography have at least one false-positive test after ten screens. The estimate for European women screened ten times biennially is much lower. We evaluate to what extent screening interval, mammogram type, and statistical methods, can explain the reported differences., Methods: We included all screens from women first screened at age 50-69 years in the US Breast Cancer Surveillance Consortium (BCSC) (n=99,455) between 1996-2010, and from two population-based mammography screening programs in Denmark (n=230,452 and n=400,204), between 1991-2012 and 1993-2013, respectively. Model-based cumulative false-positive risks were computed for the entire sample, using two statistical methods (Hubbard Njor) previously used to estimate false-positive risks in the US and Europe., Results: Empirical cumulative risk of at least one false-positive test after eight (annual or biennial) screens was 41.9% in BCSC, 16.1% in Copenhagen, and 7.4% in Funen. Variation in screening interval and mammogram type did not explain the differences by country. Using the Hubbard method, the model-based cumulative risks after eight screens was 45.1% in BCSC, 9.6% in Copenhagen, and 8.8% in Funen. Using the Njor method, these risks were estimated to be 43.6, 10.9 and 8.0%., Conclusion: Choice of statistical method, screening interval and mammogram type does not explain the substantial differences in cumulative false-positive risk between the US and Europe., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Although healthy women aged 65 years have a life expectancy of 20 years, there is a paucity of data on the performance of digital screening mammography among these women. The authors examined the performance and outcomes of digital screening mammography among a national group of women aged ≥65 years., Methods: From Breast Cancer Surveillance Consortium data for the years 2005 to 2011, the authors included 296,496 full-field digital screening mammograms among 133,042 women ages ≥65 years without a history of breast cancer. Sensitivity, specificity, positive predictive value (PPV1 ), recall rates, and 95% confidence intervals (95% CIs) were calculated across the spectrum of age and breast density. Multivariate logistic regression was used to compare mammography accuracy, cancer-detection rates (CDRs), and tumor characteristics by age and breast density., Results: Multivariate analyses revealed a significant decrease in the recall rate with age (P for linear trend [Ptrend ] < .001) and significant increases in specificity, PPV1 , and CDR with age (Ptrend  < .001, Ptrend  < .001, and Ptrend  = .01, respectively). Sensitivity did not vary significantly with age. Among women with cancer, the proportion with invasive disease increased with age from 76% at ages 65 to 74 years to 81% at ages ≥80 years. There was a higher proportion of late stage cancers and positive lymph nodes among women ages 65 to 74 years compared with women in the older age groups., Conclusions: The specificity, PPV1 , recall rate, and CDR of digital screening mammography improved with increased age. In addition, as age increased, the proportion of women with invasive versus ductal carcinoma in situ rose, whereas the proportion of women with positive lymph nodes decreased., (© 2014 American Cancer Society.)