Artificial Intelligence for Breast Cancer Risk Assessment.

Breast cancer risk prediction models based on common clinical risk factors are used to identify women eligible for high-risk screening and prevention. Unfortunately, these models have only modest discriminatory accuracy with disparities in performance in underrepresented race and ethnicity groups. The field of artificial intelligence (AI) and deep learning are rapidly advancing the field of breast cancer risk prediction with the development of mammography-based AI breast cancer risk models. Early studies suggest mammography-based AI risk models may perform better than traditional risk factor-based models with more equitable performance.

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

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

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

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

Clinical Benefits, Harms, and Cost-Effectiveness of Breast Cancer Screening for Survivors of Childhood Cancer Treated With Chest Radiation : A Comparative Modeling Study.

BACKGROUND: Surveillance with annual mammography and breast magnetic resonance imaging (MRI) is recommended for female survivors of childhood cancer treated with chest radiation, yet benefits, harms, and costs are uncertain. OBJECTIVE: To compare the benefits, harms, and cost-effectiveness of breast cancer screening strategies in childhood cancer survivors. DESIGN: Collaborative simulation modeling using 2 Cancer Intervention and Surveillance Modeling Network breast cancer models. DATA SOURCES: Childhood Cancer Survivor Study and published data. TARGET POPULATION: Women aged 20 years with a history of chest radiotherapy. TIME HORIZON: Lifetime. PERSPECTIVE: Payer. INTERVENTION: Annual MRI with or without mammography, starting at age 25, 30, or 35 years. OUTCOME MEASURES: Breast cancer deaths averted, false-positive screening results, benign biopsy results, and incremental cost-effectiveness ratios (ICERs). RESULTS OF BASE-CASE ANALYSIS: Lifetime breast cancer mortality risk without screening was 10% to 11% across models. Compared with no screening, starting at age 25 years, annual mammography with MRI averted the most deaths (56% to 71%) and annual MRI (without mammography) averted 56% to 62%. Both strategies had the most screening tests, false-positive screening results, and benign biopsy results. For an ICER threshold of less than $100 000 per quality-adjusted life-year gained, screening beginning at age 30 years was preferred. RESULTS OF SENSITIVITY ANALYSIS: Assuming lower screening performance, the benefit of adding mammography to MRI increased in both models, although the conclusions about preferred starting age remained unchanged. LIMITATION: Elevated breast cancer risk was based on survivors diagnosed with childhood cancer between 1970 and 1986. CONCLUSION: Early initiation (at ages 25 to 30 years) of annual breast cancer screening with MRI, with or without mammography, might reduce breast cancer mortality by half or more in survivors of childhood cancer. PRIMARY FUNDING SOURCE: American Cancer Society and National Institutes of Health.

Long-Term Outcomes and Cost-Effectiveness of Breast Cancer Screening With Digital Breast Tomosynthesis in the United States.

BACKGROUND: Digital breast tomosynthesis (DBT) is increasingly being used for routine breast cancer screening. We projected the long-term impact and cost-effectiveness of DBT compared to conventional digital mammography (DM) for breast cancer screening in the United States. METHODS: Three Cancer Intervention and Surveillance Modeling Network breast cancer models simulated US women ages 40 years and older undergoing breast cancer screening with either DBT or DM starting in 2011 and continuing for the lifetime of the cohort. Screening performance estimates were based on observational data; in an alternative scenario, we assumed 4% higher sensitivity for DBT. Analyses used federal payer perspective; costs and utilities were discounted at 3% annually. Outcomes included breast cancer deaths, quality-adjusted life-years (QALYs), false-positive examinations, costs, and incremental cost-effectiveness ratios (ICERs). RESULTS: Compared to DM, DBT screening resulted in a slight reduction in breast cancer deaths (range across models 0-0.21 per 1000 women), small increase in QALYs (1.97-3.27 per 1000 women), and a 24-28% reduction in false-positive exams (237-268 per 1000 women) relative to DM. ICERs ranged from $195 026 to $270 135 per QALY for DBT relative to DM. When assuming 4% higher DBT sensitivity, ICERs decreased to $130 533-$156 624 per QALY. ICERs were sensitive to DBT costs, decreasing to $78 731 to $168 883 and $52 918 to $118 048 when the additional cost of DBT was reduced to $36 and $26 (from baseline of $56), respectively. CONCLUSION: DBT reduces false-positive exams while achieving similar or slightly improved health benefits. At current reimbursement rates, the additional costs of DBT screening are likely high relative to the benefits gained; however, DBT could be cost-effective at lower screening costs.

Projected Effects of Radiation-Induced Cancers on Life Expectancy in Patients Undergoing CT Surveillance for Limited-Stage Hodgkin Lymphoma: A Markov Model.

OBJECTIVE: Patients with limited-stage Hodgkin lymphoma (HL) undergo frequent posttreatment surveillance CT examinations, raising concerns about the cumulative magnitude of radiation exposure. The purpose of this study was to project radiation-induced cancer risks relative to competing risks of HL and account for the differential timing of each. MATERIALS AND METHODS: We adapted a previously developed Markov model to project lifetime mortality risks and life expectancy losses due to HL versus radiation-induced cancers in HL patients undergoing surveillance CT. In the base case, we modeled 35-year-old men and women undergoing seven CT examinations of the chest, abdomen, and pelvis over 5 years. Radiation-induced cancer risks and deaths for 17 organ systems were modeled using an organ-specific approach, accounting for specific anatomy exposed at CT. Cohorts of 20-, 50-, and 65-year-old men and women were evaluated in secondary analyses. Markov chain Monte Carlo methods were used to estimate the uncertainty of radiation risk projections. RESULTS: For 35-year-old adults, we projected 3324/100,000 (men) and 3345/100,000 (women) deaths from recurrent lymphoma and 245/100,000 (men, 95% uncertainty interval [UI]: 121-369) and 317/100,000 (women, 95% UI: 202-432) radiation-induced cancer deaths. Discrepancies in life expectancy losses between HL (428 days in men, 482 days in women) and radiation-induced cancers (11.6 days in men, [95% UI: 5.7-17.5], 15.6 days in women [95% UI: 9.8-21.4]) were proportionately greater because of the delayed timing of radiation-induced cancers relative to recurrent HL. Deaths and life expectancy losses from radiation-induced cancers were highest in the youngest cohorts. CONCLUSION: Given the low rate of radiation-induced cancer deaths associated with CT surveillance, modest CT benefits would justify its use in patients with limited-stage HL.

Personalizing annual lung cancer screening for patients with chronic obstructive pulmonary disease: A decision analysis.

BACKGROUND: Lung cancer screening with annual chest computed tomography (CT) is recommended for current and former smokers with a ≥30-pack-year smoking history. Patients with chronic obstructive pulmonary disease (COPD) are at increased risk of developing lung cancer and may benefit from screening at lower pack-year thresholds. METHODS: We used a previously validated simulation model to compare the health benefits of lung cancer screening in current and former smokers ages 55-80 with ≥30 pack-years with hypothetical programs using lower pack-year thresholds for individuals with COPD (≥20, ≥10, and ≥1 pack-years). Calibration targets for COPD prevalence and associated lung cancer risk were derived using the Framingham Offspring Study limited data set. We performed sensitivity analyses to evaluate the stability of results across different rates of adherence to screening, increased competing mortality risk from COPD, and increased surgical ineligibility in individuals with COPD. The primary outcome was projected life expectancy. RESULTS: Programs using lower pack-year thresholds for individuals with COPD yielded the highest life expectancy gains for a given number of screens. Highest life expectancy was achieved when lowering the pack-year threshold to ≥1 pack-year for individuals with COPD, which dominated all other screening strategies. These results were stable across different adherence rates to screening and increases in competing mortality risk for COPD and surgical ineligibility. CONCLUSIONS: Current and former smokers with COPD may disproportionately benefit from lung cancer screening. A lower pack-year threshold for screening eligibility may benefit this high-risk patient population.

Cost-effectiveness of alternating magnetic resonance imaging and digital mammography screening in BRCA1 and BRCA2 gene mutation carriers.

BACKGROUND: Current clinical guidelines recommend earlier, more intensive breast cancer screening with both magnetic resonance imaging (MRI) and mammography for women with breast cancer susceptibility gene (BRCA) mutations. Unspecified details of screening schedules are a challenge for implementing guidelines. METHODS: A Markov Monte Carlo computer model was used to simulate screening in asymptomatic women who were BRCA1 and BRCA2 mutation carriers. Three dual-modality strategies were compared with digital mammography (DM) alone: 1) DM and MRI alternating at 6-month intervals beginning at age 25 years (Alt25), 2) annual MRI beginning at age 25 years with alternating DM added at age 30 years (MRI25/Alt30), and 3) DM and MRI alternating at 6-month intervals beginning at age 30 years (Alt30). Primary outcomes were quality-adjusted life years (QALYs), lifetime costs (in 2010 US dollars), and incremental cost-effectiveness (dollars per QALY gained). Additional outcomes included potential harms of screening, and lifetime costs stratified into component categories (screening and diagnosis, treatment, mortality, and patient time costs). RESULTS: All 3 dual-modality screening strategies increased QALYs and costs. Alt30 screening had the lowest incremental costs per additional QALY gained (BRCA1, $74,200 per QALY; BRCA2, $215,700 per QALY). False-positive test results increased substantially with dual-modality screening and occurred more frequently in BRCA2 carriers. Downstream savings in both breast cancer treatment and mortality costs were outweighed by increases in up-front screening and diagnosis costs. The results were influenced most by estimates of breast cancer risk and MRI costs. CONCLUSIONS: Alternating MRI and DM screening at 6-month intervals beginning at age 30 years was identified as a clinically effective approach to applying current guidelines, and was more cost-effective in BRCA1 gene mutation carriers compared with BRCA2 gene mutation carriers.

Using radiation risk models in cancer screening simulations: important assumptions and effects on outcome projections.

PURPOSE: To evaluate the effect of incorporating radiation risk into microsimulation (first-order Monte Carlo) models for breast and lung cancer screening to illustrate effects of including radiation risk on patient outcome projections. MATERIALS AND METHODS: All data used in this study were derived from publicly available or deidentified human subject data. Institutional review board approval was not required. The challenges of incorporating radiation risk into simulation models are illustrated with two cancer screening models (Breast Cancer Model and Lung Cancer Policy Model) adapted to include radiation exposure effects from mammography and chest computed tomography (CT), respectively. The primary outcome projected by the breast model was life expectancy (LE) for BRCA1 mutation carriers. Digital mammographic screening beginning at ages 25, 30, 35, and 40 years was evaluated in the context of screenings with false-positive results and radiation exposure effects. The primary outcome of the lung model was lung cancer-specific mortality reduction due to annual screening, comparing two diagnostic CT protocols for lung nodule evaluation. The Metropolis-Hastings algorithm was used to estimate the mean values of the results with 95% uncertainty intervals (UIs). RESULTS: Without radiation exposure effects, the breast model indicated that annual digital mammography starting at age 25 years maximized LE (72.03 years; 95% UI: 72.01 years, 72.05 years) and had the highest number of screenings with false-positive results (2.0 per woman). When radiation effects were included, annual digital mammography beginning at age 30 years maximized LE (71.90 years; 95% UI: 71.87 years, 71.94 years) with a lower number of screenings with false-positive results (1.4 per woman). For annual chest CT screening of 50-year-old females with no follow-up for nodules smaller than 4 mm in diameter, the lung model predicted lung cancer-specific mortality reduction of 21.50% (95% UI: 20.90%, 22.10%) without radiation risk and 17.75% (95% UI: 16.97%, 18.41%) with radiation risk. CONCLUSION: Because including radiation exposure risk can influence long-term projections from simulation models, it is important to include these risks when conducting modeling-based assessments of diagnostic imaging.

Intentional and unintentional nonadherence to antihypertensive medication.

BACKGROUND: Hypertension is poorly controlled in the US due to medication nonadherence. Recent evidence suggests that nonadherence can be classified as intentional or unintentional and different patient characteristics, such as the experience of adverse effects, may be associated with each. OBJECTIVE: To examine associations between patient characteristics, including reported adverse effects, and both intentional and unintentional nonadherence among 588 hypertensive patients. METHODS: Baseline data from a clinical trial, the Veterans' Study To Improve the Control of Hypertension, were examined. Intentional and unintentional nonadherence were assessed using a self-report measure. Participants were presented with a list of adverse effects commonly associated with antihypertensive medication and asked to indicate which symptoms they had experienced. Logistic regression analyses were used to examine adjusted associations between patient characteristics and type of nonadherence. RESULTS: Approximately 31% of patients reported unintentional nonadherence and 9% reported intentional nonadherence. Non-white participants, individuals without diabetes mellitus, and individuals reporting > or = 5 adverse effects were more likely to report intentional nonadherence than their counterparts. Individuals with less than a 10th-grade education and non-white participants were more likely to report unintentional nonadherence than their counterparts. When symptoms of increased urination and wheezing/shortness of breath were reported, patients were more likely to report intentional and unintentional nonadherence compared with those who were adherent. Unintentional nonadherence was also associated with reports of dizziness and rapid pulse. CONCLUSIONS: Both intentional and unintentional nonadherence are common and related to perceived adverse effects. Furthermore, different interventions may be necessary to improve adherence in unintentionally and intentionally nonadherent patients.