Estimating Breast Cancer Overdiagnosis After Screening Mammography Among Older Women in the United States.

BACKGROUND: Overdiagnosis is increasingly recognized as a harm of breast cancer screening, particularly for older women. OBJECTIVE: To estimate overdiagnosis associated with breast cancer screening among older women by age. DESIGN: Retrospective cohort study comparing the cumulative incidence of breast cancer among older women who continued screening in the next interval with those who did not. Analyses used competing risk models, stratified by age. SETTING: Fee-for-service Medicare claims, linked to the SEER (Surveillance, Epidemiology, and End Results) program. PATIENTS: Women 70 years and older who had been recently screened. MEASUREMENTS: Breast cancer diagnoses and breast cancer death for up to 15 years of follow-up. RESULTS: This study included 54 635 women. Among women aged 70 to 74 years, the adjusted cumulative incidence of breast cancer was 6.1 cases (95% CI, 5.7 to 6.4) per 100 screened women versus 4.2 cases (CI, 3.5 to 5.0) per 100 unscreened women. An estimated 31% of breast cancer among screened women were potentially overdiagnosed. For women aged 75 to 84 years, cumulative incidence was 4.9 (CI, 4.6 to 5.2) per 100 screened women versus 2.6 (CI, 2.2 to 3.0) per 100 unscreened women, with 47% of cases potentially overdiagnosed. For women aged 85 and older, the cumulative incidence was 2.8 (CI, 2.3 to 3.4) among screened women versus 1.3 (CI, 0.9 to 1.9) among those not, with up to 54% overdiagnosis. We did not see statistically significant reductions in breast cancer-specific death associated with screening. LIMITATIONS: This study was designed to estimate overdiagnosis, limiting our ability to draw conclusions on all benefits and harms of screening. Unmeasured differences in risk for breast cancer and differential competing mortality between screened and unscreened women may confound results. Results were sensitive to model specifications and definition of a screening mammogram. CONCLUSION: Continued breast cancer screening was associated with greater incidence of breast cancer, suggesting overdiagnosis may be common among older women who are diagnosed with breast cancer after screening. Whether harms of overdiagnosis are balanced by benefits and for whom remains an important question. PRIMARY FUNDING SOURCE: National Cancer Institute.

Comparative Effectiveness of Digital Breast Tomosynthesis and Mammography in Older Women.

BACKGROUND: Digital breast tomosynthesis (DBT) has become a prevalent mode of breast cancer screening in recent years. Although older women are commonly screened for breast cancer, little is known about screening outcomes using DBT among older women. OBJECTIVE: To assess proximal screening outcomes with DBT compared to traditional two-dimensional(2-D) mammography among women 67-74 and women 75 and older. DESIGN: Cohort study. PARTICIPANTS: Medicare fee-for-service beneficiaries aged 67 years and older with no history of prior cancer who received a screening mammogram in 2015. MAIN MEASURES: Use of subsequent imaging (ultrasound and diagnostic mammography) as an indication of recall, breast cancer detection, and characteristics of breast cancer at the time of diagnosis. Analyses used weighted logistic regression to adjust for potential confounders. KEY RESULTS: Our study included 26,406 women aged 67-74 and 17,001 women 75 and older who were screened for breast cancer. Among women 75 and older, the rate of subsequent imaging among women screened with DBT did not differ significantly from 2-D mammography (91.8 versus 97.0 per 1,000 screening mammograms, p=0.37). In this age group, DBT was associated with 2.1 additional cancers detected per 1,000 screening mammograms compared to 2D (11.5 versus 9.4, p=0.003), though these additional cancers were almost exclusively in situ and stage I invasive cancers. For women 67-74 years old, DBT was associated with a higher rate of subsequent imaging than 2-D mammography (113.9 versus 100.3, p=0.004) and a higher rate of stage I invasive cancer detection (4.7 versus 3.7, p=0.002), but not other stages. CONCLUSIONS: Breast cancer screening with DBT was not associated with lower rates of subsequent imaging among older women. Most additional cancers detected with DBT were early stage. Whether detecting these additional early-stage cancers among older women improves health outcomes remains uncertain.

Understanding Regional Variation in the Cost of Breast Cancer Screening Among Privately Insured Women in the United States.

BACKGROUND: Breast cancer screening for women aged 40-49 years is prevalent and costly, with costs varying substantially across US regions. Newer approaches to mammography may improve cancer detection but also increase screening costs. We assessed factors associated with regional variation in screening costs. METHODS: We used Blue Cross Blue Shield Axis, a large US commercial claims database accessed through secure portal, to assess regional variation in screening utilization and costs. We included screening mammography±digital breast tomosynthesis (DBT), screening ultrasound, diagnostic mammography±DBT, diagnostic ultrasound, magnetic resonance imaging and biopsy, and evaluated their utilization and costs. We assessed regional variation in annual per-screened-beneficiary costs and examined potential savings from reducing regional variation. RESULTS: Of the 2,257,393 privately insured women, 41.2% received screening mammography in 2017 (range: 26.6%-54.2% across regions). Wide regional variation was found in the DBT proportion (0.7%-91.1%) and mean costs of DBT ($299; range: $113-714) and 2-dimensional (D) mammograms ($213; range: $107-471). In one-fourth of the regions, the mean DBT cost was lower than the mean 2D mammography cost in the full sample. Regional variation in the per-screened-beneficiary cost (mean: $353; range: $151-751) was mainly attributable to variation in the cost of DBT (accounting for 23.4% of regional variation) and 2D mammography (23.0%). Reducing regional variation by decreasing the highest values to the national mean was projected to save $79-335 million annually. CONCLUSIONS: The mean mammogram cost for privately insured women ages 40-49 varies 7-fold across regions, driving substantial variation in breast cancer screening costs. Reducing this regional variation would substantially decrease the screening costs.

Dense Breast Notification Laws, Education, and Women's Awareness and Knowledge of Breast Density: a Nationally Representative Survey.

BACKGROUND: To date, 38 states have enacted dense breast notification (DBN) laws mandating that mammogram reports include language informing women of risks related to dense breast tissue. OBJECTIVE: Nationally representative survey to assess the association between residing in a state with a DBN law and women's awareness and knowledge about breast density, and breast cancer anxiety. DESIGN: Internet survey conducted in 2018 with participants in KnowledgePanel®, an online research panel. PARTICIPANTS: English-speaking US women ages 40-59 years without a personal history of breast cancer who had received at least one screening mammogram (N = 1928; survey completion rate 68.2%). MAIN MEASURES: (1) Reported history of increased breast density, (2) knowledge of the increased risk of breast cancer with dense breasts, (3) knowledge of the masking effect of dense breasts on mammography, and (4) breast cancer anxiety. KEY RESULTS: Women residing in DBN states were more likely to report increased breast density (43.6%) compared with women residing in non-DBN states (32.7%, p < 0.01, adjusted odds ratio, 1.70, 95% CI,1.34-2.17). Interaction effect between DBN states and education status showed that the impact of DBN on women's reporting of dense breasts was significant for women with greater than high school education, but not among women with a high school education or less (p value = 0.01 for interaction). Only 23.0% of women overall knew that increased breast density was associated with a higher risk of breast cancer, and 68.0% of women understood that dense breasts decreased the sensitivity of mammography. There were no significant differences between women in DBN states and non-DBN states for these outcomes, or for breast cancer-related anxiety. CONCLUSIONS: State DBN laws were not associated with increased understanding of the clinical implications of breast density. DBN laws were associated with a higher likelihood of women reporting increased breast density, though not among women with lower education.

Association of State Dense Breast Notification Laws With Supplemental Testing and Cancer Detection After Screening Mammography.

OBJECTIVES: To evaluate the association of state dense breast notification (DBN) laws with use of supplemental tests and cancer diagnosis after screening mammography. METHODS: We examined screening mammograms (n = 1 441 544) performed in 2014 and 2015 among privately insured women aged 40 to 59 years living in 9 US states that enacted DBN laws in 2014 to 2015 and 25 US states with no DBN law in effect. DBN status at screening mammography was categorized as no DBN, generic DBN, and DBN that mandates notification of possible benefits of supplemental screening (DBN+SS). We used logistic regression to examine the change in rate of supplemental ultrasound, magnetic resonance imaging, breast biopsy, and breast cancer detection. RESULTS: DBN+SS laws were associated with 10.5 more ultrasounds per 1000 mammograms (95% CI = 3.0, 17.6 per 1000; P = .006) and 0.37 more breast cancers detected per 1000 mammograms (95% CI = 0.05, 0.69 per 1000; P = .02) compared with no DBN law. No significant differences were found for generic DBN laws in either ultrasound or cancer detection. CONCLUSIONS: DBN legislation is associated with increased use of ultrasound and cancer detection after implementation only when notification of the possible benefits of supplemental screening is required.

A National study of burdensome health care costs among non-elderly Americans.

BACKGROUND: Rising health care costs and increased cost sharing have resulted in significant medical expenses for many Americans. The goal of this study was to describe the prevalence of and risk factors for burdensome health care costs among non-elderly Americans. METHODS: This was a cross sectional study of a nationally representative sample of non-elderly Americans. We used survey data previously collected by the Kaiser Family Foundation. We used logistic regression to identify key risk factors for burdensome health care costs and to assess whether risk factors differ according to age within our study population. For analyses comparing younger and middle-aged adults, we compared participants ages 18-39 (younger Americans) to those ages 40-64 (middle-aged Americans). RESULTS: Our study population included 5,493 participants. Twenty seven percent of participants reported difficulty paying medical bills, a prevalence that did not differ by age. Low income, lack of health insurance, and poor health were independently associated with difficulty paying medical bills after controlling for demographic covariates. Both younger and middle-aged adults were likely to experience burdensome health care costs at low incomes. At moderate incomes, risk fell for middle-aged adults, but remained high for younger adults (ORmiddle-age 1.40, 95% CI 1.12-1.75, ORyounger 2.48, 95% CI 1.73-3.57, p value for interaction 0.004). Younger adults without insurance were at risk for accruing burdensome costs compared to their insured counterparts (OR 2.61, 95% CI 1.96-3.47). Middle-aged adults without insurance, though, had an even higher risk (OR 3.82, 95% CI 2.93-4.97, p value for interaction 0.037). CONCLUSIONS: Both younger and middle-aged adults commonly report difficulty paying medical bills. Younger adults remain vulnerable to burdensome medical costs even when earning moderate incomes. Middle-aged adults, however, are more likely to encounter burdensome costs when uninsured. These findings suggest that younger and middle-aged adults experience distinct vulnerabilities and may benefit differentially from health reform efforts intended to expand coverage and limit out-of-pocket expenses.

Digital Interventions to Support Lung Cancer Screening: A Systematic Review.

INTRODUCTION: Lung cancer remains a leading cause of cancer-related deaths globally. Lung cancer screening (LCS) with low-dose computed tomography (LDCT) can reduce lung cancer mortality, but its adoption in the U.S. has been limited. Digital interventions have the potential to improve uptake of LCS. This systematic review aims to summarize the evidence for the effectiveness of digital interventions in promoting LCS. METHODS: A systematic search of three electronic databases (PubMed, Embase, and Medline) was conducted to identify studies published between January 2014 and May 2023. Studies were reviewed and abstracted between February 2023 and July 2023. Outcomes related to knowledge, decision-making and screening were measured. Study quality was assessed using the Joanna Briggs Institute (JBI) critical appraisal tools. RESULTS: Of 1,979 screened articles, 30 studies were included in this review. Digital interventions evaluated included decision aids (n=20), electronic health record (EHR)-based interventions (n=7), social media campaigns and mobile applications (n=3). Decision aids were the most commonly studied digital interventions, with most studies showing improved knowledge (13/13) and reduced decisional conflict (7/9) but most did not show a substantial change in screening use. Fewer studies tested clinician-facing or multi-level interventions. DISCUSSION: Digital interventions, particularly decision aids, have shown promise in improving knowledge and the quality of decision-making around LCS. However, few interventions have been shown to substantially alter screening behavior and few clinician-facing or multi-level interventions have been rigorously tested. Further research is needed to develop effective tools for engaging patients in LCS, to compare the efficacy of different interventions, and evaluate implementation strategies in diverse healthcare settings.

Incarceration and screen-detectable cancer diagnosis among adults in Connecticut.

Although incarcerated adults are at elevated risk of dying from cancer, little is known about cancer screening in carceral settings. This study compared stage-specific incidence of screen-detectable cancers among incarcerated and recently released people with the general population, as a reflection of screening practices. We calculated the age- and sex-standardized incidence ratios (SIR) for early- and late-stage cancers for incarcerated and recently released adults compared to the general Connecticut population between 2005 and 2016. Our sample included 143 cancer cases among those incarcerated, 406 among those recently released, and 201 360 in the general population. The SIR for early-stage screen-detectable cancers was lower among incarcerated (SIR = 0.28, 95% CI = 0.17 to 0.43) and recently released (SIR = 0.69, 95% CI = 0.51 to 0.88) individuals than the general population. Incidence of late-stage screen-detectable cancer was lower during incarceration (SIR = 0.51, 95% CI = 0.27 to 0.88) but not after release (SIR = 1.32, 95% CI = 0.93 to 1.82). Findings suggest that underscreening and underdetection of cancer may occur in carceral settings.

ACR Appropriateness Criteria® Female Breast Cancer Screening: 2023 Update.

Early detection of breast cancer from regular screening substantially reduces breast cancer mortality and morbidity. Multiple different imaging modalities may be used to screen for breast cancer. Screening recommendations differ based on an individual's risk of developing breast cancer. Numerous factors contribute to breast cancer risk, which is frequently divided into three major categories: average, intermediate, and high risk. For patients assigned female at birth with native breast tissue, mammography and digital breast tomosynthesis are the recommended method for breast cancer screening in all risk categories. In addition to the recommendation of mammography and digital breast tomosynthesis in high-risk patients, screening with breast MRI is recommended. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.

European genetic ancestry is associated with a decreased risk of lupus nephritis.

OBJECTIVE: African Americans, East Asians, and Hispanics with systemic lupus erythematosus (SLE) are more likely to develop renal disease than are SLE patients of European descent. This study was undertaken to investigate whether European genetic ancestry protects against the development of lupus nephritis, with the aim of exploring the genetic and socioeconomic factors that might explain this effect. METHODS: This was a cross-sectional study of SLE patients from a multiethnic case collection. Participants were genotyped for 126 single-nucleotide polymorphisms (SNPs) informative for ancestry. A subset of participants was also genotyped for 80 SNPs in 14 candidate genes for renal disease in SLE. Logistic regression was used to test the association between European ancestry and renal disease. Analyses were adjusted for continental ancestries, socioeconomic status (SES), and candidate genes. RESULTS: Participants (n = 1,906) had, on average, 62.4% European, 15.8% African, 11.5% East Asian, 6.5% Amerindian, and 3.8% South Asian ancestry. Among the participants, 656 (34%) had renal disease. A 10% increase in the proportion of European ancestry estimated in each participant was associated with a 15% reduction in the odds of having renal disease, after adjustment for disease duration and sex (odds ratio 0.85, 95% confidence interval 0.82-0.87; P = 1.9 × 10(-30) ). Adjustment for other genetic ancestries, measures of SES, or SNPs in the genes most associated with renal disease (IRF5 [rs4728142], BLK [rs2736340], STAT4 [rs3024912], and HLA-DRB1*0301 and DRB1*1501) did not substantively alter this relationship. CONCLUSION: European ancestry is protective against the development of renal disease in SLE, an effect that is independent of other genetic ancestries, candidate risk alleles, and socioeconomic factors.

Cancer incidence among incarcerated and formerly incarcerated individuals: A statewide retrospective cohort study.

BACKGROUND: Cancer incidence among individuals with incarceration exposure has been rarely studied due to the absence of linked datasets. This study examined cancer incidence during incarceration and postincarceration compared to the general population using a statewide linked cohort. METHODS: We constructed a retrospective cohort from a linkage of state tumor registry and correctional system data for Connecticut residents from 2005 to 2016, and identified cancers diagnosed during and within 12 months postincarceration. We estimated incidence rates (including for screen-detectable cancers) and calculated the standardized incidence ratios (SIR) for the incarcerated and recently released populations, relative to the general population. We also examined cancer incidence by race and ethnicity within each group. RESULTS: Cancer incidence was lower in incarcerated individuals (SIR = 0.64, 95% CI 0.56-0.72), but higher in recently released individuals (SIR = 1.34, 95% CI 1.23-1.47) compared with the general population, and across all race and ethnic strata. Similarly, nonscreen-detectable cancer incidence was lower in incarcerated and higher in recently released populations compared to the general population. However, non-Hispanic Black individuals had elevated incidence of screen-detectable cancers compared with non-Hispanic White individuals across all three populations (incarcerated, SIR = 1.66, 95% CI 1.03-2.53; recently released, SIR = 1.83, 95% CI 1.32-2.47; and general population, SIR = 1.18, 95% CI 1.16-1.21). CONCLUSION: Compared with the general population, incarcerated persons have a lower cancer incidence, whereas recently released persons have a higher cancer incidence. Irrespective of incarceration status, non-Hispanic Black individuals have a higher incidence of screen-detectable cancers compared with non-Hispanic White individuals. Supplemental studies examining cancer screening and diagnoses during incarceration are needed to discern the reasons for observed disparities in incidence.

ACR Appropriateness Criteria® Routine Chest Imaging.

Routine chest imaging has been used to identify unknown or subclinical cardiothoracic abnormalities in the absence of symptoms. Various imaging modalities have been suggested for routine chest imaging. We review the evidence for or against the use of routine chest imaging in different clinical scenarios. This document aims to determine guidelines for the use of routine chest imaging as initial imaging for hospital admission, initial imaging prior to noncardiothoracic surgery, and surveillance imaging for chronic cardiopulmonary disease. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.

Lost to follow up?: A qualitative study of why some patients do not pursue lung cancer screening.

Although national guidelines recommend lung cancer screening for adults at high risk, only a small proportion of eligible adults in the US have been screened. The goal of this study was to understand barriers to screening among a specific but important population: patients who have been referred for screening, but who have not completed the test. We used semi-structured interviews to explore barriers to screening among patients at two academic, safety-net primary care practices. We included patients who had been referred for screening at least 6 months prior but who had not completed the test. Among interviewees (N = 16) a consistent theme was a lack of knowledge about the purpose and process of screening. Despite being referred for lung cancer screening, participants expressed that they knew little about how screening was performed or what it was intended to achieve. Preferences and values also played a role in why some participants did not return for screening. Our findings suggest that lack of knowledge about screening is an important barrier to use, as patients are unlikely to prioritize a test if they know little about it.

The role of lung cancer risk and comorbidity in lung cancer screening use.

Although lung cancer screening (LCS) with low dose computed tomography has been shown to reduce lung cancer mortality, benefits and harms of screening vary among eligible adults. The goal of this study was to evaluate whether LCS is more commonly used among populations most likely to benefit, namely adults with high lung cancer risk and low comorbidity. In this cohort study of patients eligible for LCS, we used data from the electronic health record to evaluate the relationship between lung cancer risk, comorbidity, and receipt of LCS. We also evaluated use of diagnostic chest CT. Analyses used a nonparametric test for trend across quartiles of lung cancer risk and comorbidity. The study sample included 551 LCS-eligible adults who were followed for a mean 2.9 years (SD 1.6 years). A cumulative 190 (34 %) received at least 1 LCS, and 141 (26 %) had a diagnostic chest CT. Receipt of LCS increased across quartiles of lung cancer risk (5 per 100 person years in the lowest quartile vs 13 per 100 person-years in the highest, p < 0.001 for test of trend). LCS receipt decreased across increasing quartiles of comorbidity (14 vs 8 per 100 person-years, p = 0.008). Diagnostic CT was more common in among patient with higher levels of comorbidity (15 vs 5 per 100 person-years, p < 0.001). In conclusion, lung cancer screening was more commonly used in patients with greater lung cancer risk and lower comorbidity. Results suggest that both patient characteristics and use of diagnostic imaging may shape current patterns of LCS use.

Artificial Intelligence in Breast Cancer Screening: Evaluation of FDA Device Regulation and Future Recommendations.

Importance: Contemporary approaches to artificial intelligence (AI) based on deep learning have generated interest in the application of AI to breast cancer screening (BCS). The US Food and Drug Administration (FDA) has approved several next-generation AI products indicated for BCS in recent years; however, questions regarding their accuracy, appropriate use, and clinical utility remain. Objectives: To describe the current FDA regulatory process for AI products, summarize the evidence used to support FDA clearance and approval of AI products indicated for BCS, consider the advantages and limitations of current regulatory approaches, and suggest ways to improve the current system. Evidence Review: Premarket notifications and other publicly available documents used for FDA clearance and approval of AI products indicated for BCS from January 1, 2017, to December 31, 2021. Findings: Nine AI products indicated for BCS for identification of suggestive lesions and mammogram triage were included. Most of the products had been cleared through the 510(k) pathway, and all clearances were based on previously collected retrospective data; 6 products used multicenter designs; 7 products used enriched data; and 4 lacked details on whether products were externally validated. Test performance measures, including sensitivity, specificity, and area under the curve, were the main outcomes reported. Most of the devices used tissue biopsy as the criterion standard for BCS accuracy evaluation. Other clinical outcome measures, including cancer stage at diagnosis and interval cancer detection, were not reported for any of the devices. Conclusions and Relevance: The findings of this review suggest important gaps in reporting of data sources, data set type, validation approach, and clinical utility assessment. As AI-assisted reading becomes more widespread in BCS and other radiologic examinations, strengthened FDA evidentiary regulatory standards, development of postmarketing surveillance, a focus on clinically meaningful outcomes, and stakeholder engagement will be critical for ensuring the safety and efficacy of these products.

Insurance Coverage Mandates and the Adoption of Digital Breast Tomosynthesis.

Importance: Digital breast tomosynthesis (DBT) is a breast cancer screening modality that has gained popularity in recent years. Although insurance coverage for DBT is not mandated under the Patient Protection and Affordable Care Act, several states have required coverage without cost sharing for private insurers. Objective: To evaluate the association between state-level insurance coverage mandates for DBT and changes in DBT use, price, and out-of-pocket payments. Design, Setting, and Participants: This cohort study used an event-study design with repeated cross-sectional observations of US states. Data were obtained from the Blue Cross Blue Shield Axis database for commercially insured women aged 40 to 64 years who underwent screening mammography between January 1, 2015, and June 30, 2019. Data were analyzed between January 14, 2021, and January 20, 2022. Interventions: Passage of state-level legislation requiring insurance coverage of DBT. Main Outcomes and Measures: Change in DBT use among women screened for breast cancer, overall DBT price, and out-of-pocket payments for DBT in states with mandates for coverage of DBT compared with states that did not pass legislation. Results: This study included 9 604 084 screening mammograms from 5 754 123 women (mean [SD] age, of 53 [6.7] years). During the study period, 15 states enacted DBT coverage mandates and 34 states did not. In states with coverage mandates, DBT use increased by 9.0 percentage points (95% CI, 1.8-16.3 percentage points; P = .02) 2 years after the mandate compared with states without coverage mandates. Coverage mandates were also associated with a net $38.7 (95% CI, $13.4-$63.9; P = .003) decrease in the mean price of DBT compared with no coverage mandates. There was no association between coverage mandates and out-of-pocket payments 2 years after mandate passage ($-2.1; 95% CI, $-5.3 to $1.0; P = .18). Conclusions and Relevance: In this cohort study, DBT coverage mandates were associated with an increase in DBT use but not with any change in out-of-pocket payments. The findings suggest that coverage mandates for DBT may have been associated with broader use but were not associated with changes in direct costs to patients.