Considerations for using potential surrogate endpoints in cancer screening trials.

The requirement of large-scale expensive cancer screening trials spanning decades creates considerable barriers to the development, commercialisation, and implementation of novel screening tests. One way to address these problems is to use surrogate endpoints for the ultimate endpoint of interest, cancer mortality, at an earlier timepoint. This Review aims to highlight the issues underlying the choice and use of surrogate endpoints for cancer screening trials, to propose criteria for when and how we might use such endpoints, and to suggest possible candidates. We present the current landscape and challenges, and discuss lessons and shortcomings from the therapeutic trial setting. It is hugely challenging to validate a surrogate endpoint, even with carefully designed clinical studies. Nevertheless, we consider whether there are candidates that might satisfy the requirements defined by research and regulatory bodies.

Cancer Stage Compared With Mortality as End Points in Randomized Clinical Trials of Cancer Screening: A Systematic Review and Meta-Analysis.

Importance: Randomized clinical trials of cancer screening typically use cancer-specific mortality as the primary end point. The incidence of stage III-IV cancer is a potential alternative end point that may accelerate completion of randomized clinical trials of cancer screening. Objective: To compare cancer-specific mortality with stage III-IV cancer as end points in randomized clinical trials of cancer screening. Design, Setting, and Participants: This meta-analysis included 41 randomized clinical trials of cancer screening conducted in Europe, North America, and Asia published through February 19, 2024. Data extracted included numbers of participants, cancer diagnoses, and cancer deaths in the intervention and comparison groups. For each clinical trial, the effect of screening was calculated as the percentage reduction between the intervention and comparison groups in the incidence of participants with cancer-specific mortality and stage III-IV cancer. Exposures: Randomization to a cancer screening test or to a comparison group in a clinical trial of cancer screening. Main Outcomes and Measures: End points of cancer-specific mortality and incidence of stage III-IV cancer were compared using Pearson correlation coefficients with 95% CIs, linear regression, and fixed-effects meta-analysis. Results: The included randomized clinical trials tested benefits of screening for breast (n = 6), colorectal (n = 11), lung (n = 12), ovarian (n = 4), prostate (n = 4), and other cancers (n = 4). Correlation between reductions in cancer-specific mortality and stage III-IV cancer varied by cancer type (I2 = 65%; P = .02). Correlation was highest for trials that screened for ovarian (Pearson ρ = 0.99 [95% CI, 0.51-1.00]) and lung (Pearson ρ = 0.92 [95% CI, 0.72-0.98]) cancers, moderate for breast cancer (Pearson ρ = 0.70 [95% CI, -0.26 to 0.96]), and weak for colorectal (Pearson ρ = 0.39 [95% CI, -0.27 to 0.80]) and prostate (Pearson ρ = -0.69 [95% CI, -0.99 to 0.81]) cancers. Slopes from linear regression were estimated as 1.15 for ovarian cancer, 0.75 for lung cancer, 0.40 for colorectal cancer, 0.28 for breast cancer, and -3.58 for prostate cancer, suggesting that a given magnitude of reduction in incidence of stage III-IV cancer produced different magnitudes of change in incidence of cancer-specific mortality (P for heterogeneity = .004). Conclusions and Relevance: In randomized clinical trials of cancer screening, incidence of late-stage cancer may be a suitable alternative end point to cancer-specific mortality for some cancer types, but is not suitable for others. These results have implications for clinical trials of multicancer screening tests.

Survival in Patients With De Novo Metastatic Prostate Cancer.

This cross-sectional study investigates trends in overall survival among patients with newly diagnosed metastatic prostate cancer in 2 national registries in the United States.

Projecting the impact of multi-cancer early detection on late-stage incidence using multi-state disease modeling.

BACKGROUND: Downstaging- reduction in late-stage incidence-has been proposed as an endpoint in randomized trials of multi-cancer early detection (MCED) tests. How downstaging depends on test performance and follow-up has been studied for some cancers but is understudied for cancers without existing screening and for MCED tests that include these cancer types. METHODS: We develop a model for cancer natural history that can be fit to registry incidence patterns under minimal inputs and can be estimated for solid cancers without existing screening. Fitted models are combined to project downstaging in MCED trials given sensitivity for early- and late-stage cancers. We fit models for 12 cancers using incidence data from the Surveillance, Epidemiology, and End Results program and project downstaging in a simulated trial under variable preclinical latencies and test sensitivities. RESULTS: A proof-of-principle lung cancer model approximated downstaging in the National Lung Screening Trial. Given published stage-specific sensitivities for 12 cancers, we projected downstaging ranging 21%-43% across plausible preclinical latencies in a hypothetical 3-screen MCED trial. Late-stage incidence reductions manifest soon after screening begins. Downstaging increases with longer early-stage latency or higher early-stage test sensitivity. CONCLUSION: Even short-term MCED trials could produce substantial downstaging given adequate early-stage test sensitivity. IMPACT: Modeling the natural histories of cancers without existing screening facilitates analysis of novel MCED products and trial designs. The framework informs expectations of MCED impact on disease stage at diagnosis and could serve as a building block for designing trials with late-stage incidence as the primary endpoint.

Prediagnostic evaluation of multicancer detection tests: Design and analysis considerations.

There is growing interest in multicancer detection (MCD) tests, which identify molecular signals in the blood indicating a potential preclinical cancer. A key stage in evaluating MCD tests is a prediagnostic performance study, in which investigators store specimens from asymptomatic persons and later test stored specimens from cancer cases and a random sample of controls to determine predictive performance. Performance metrics include cancer-specific true and false positive rates and a cancer-specific positive predictive value, with the latter compared to a decision-analytic threshold. The sample size tradeoff method, which trades imprecise targeting of the true positive rate for precise targeting of a zero false positive rate can substantially reduce sample size while increasing the lower bound of positive predictive value. For a 1-year follow-up, with ovarian cancer as the rarest cancer considered, the sample size tradeoff method yields a sample size of 163,000 compared with a sample size of 720,000 based on standard calculations. These design and analysis recommendations should be considered in planning a specimen repository and in the prediagnostic evaluation of MCD tests.

Implementation outcomes of the integrated district evidence to action (IDEAs) program to reduce neonatal mortality in central Mozambique: an application of the RE-AIM evaluation framework.

BACKGROUND: Scarce evidence exists on audit and feedback implementation processes in low-resource health systems. The Integrated District Evidence to Action (IDEAs) is a multi-component audit and feedback strategy designed to improve the implementation of maternal and child guidelines in Mozambique. We report IDEAs implementation outcomes. METHODS: IDEAs was implemented in 154 health facilities across 12 districts in Manica and Sofala provinces between 2016 and 2020 and evaluated using a quasi-experimental design guided by the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework. Reach is the proportion of pregnant women attending IDEAs facilities. Adoption is the proportion of facilities initiating audit and feedback meetings. Implementation is the fidelity to the strategy components, including readiness assessments, meetings (frequency, participation, action plan development), and targeted financial support and supervision. Maintenance is the sustainment at 12, 24, and 54 months. RESULTS: Across both provinces, 56% of facilities were exposed to IDEAs (target 57%). Sixty-nine and 73% of pregnant women attended those facilities' first and fourth antenatal consultations (target 70%). All facilities adopted the intervention. 99% of the expected meetings occurred with an average interval of 5.9 out of 6 months. Participation of maternal and child managers was high, with 3076 attending meetings, of which 64% were from the facility, 29% from the district, and 7% from the province level. 97% of expected action plans were created, and 41 specific problems were identified. "Weak diagnosis or management of obstetric complications" was identified as the main problem, and "actions to reinforce norms and protocols" was the dominant subcategory of micro-interventions selected. Fidelity to semiannual readiness assessments was low (52% of expected facilities), and in completing micro-interventions (17% were completed). Ninety-six and 95% of facilities sustained the intervention at 12 and 24 months, respectively, and 71% had completed nine cycles at 54 months. CONCLUSION: Maternal and child managers can lead audit and feedback processes in primary health care in Mozambique with high reach, adoption, and maintenance. The IDEAs strategy should be adapted to promote higher fidelity around implementing action plans and conducting readiness assessments. Adding effectiveness to these findings will help to inform strategy scale-up.

The Prostate Cancer Active Lifestyle Study (PALS): A randomized controlled trial of diet and exercise in overweight and obese men on active surveillance.

BACKGROUND: Active surveillance (AS) is increasingly used to monitor patients with lower risk prostate cancer (PCa). The Prostate Cancer Active Lifestyle Study (PALS) was a randomized controlled trial to determine whether weight loss improves obesity biomarkers on the causal pathway to progression in patients with PCa on AS. METHODS: Overweight/obese men (body mass index >25 kg/m2 ) diagnosed with PCa who elected AS were recruited. The intervention was a 6-month, individually delivered, structured diet and exercise program adapted from the Diabetes Prevention Program with a 7% weight loss goal from baseline. Control participants attended one session reviewing the US Dietary and Physical Activity Guidelines. The primary outcome was change in glucose regulation from baseline to the end of the 6-month intervention, which was measured by fasting plasma glucose, C-peptide, insulin, insulin-like growth factor 1, insulin-like growth factor binding protein-3, adiponectin, and homeostatic model assessment for insulin resistance. RESULTS: Among 117 men who were randomized, 100 completed the trial. The mean percentage weight loss was 7.1% and 1.8% in the intervention and control arms, respectively (adjusted between-group mean difference, -6.0 kg; 95% confidence interval, -8.0, -4.0). Mean percentage changes from baseline for insulin, C-peptide, and homeostatic model assessment for insulin resistance in the intervention arm were -23%, -16%, and -25%, respectively, compared with +6.9%, +7.5%, and +6.4%, respectively, in the control arm (all p for intervention effects ≤ .003). No significant between-arm differences were detected for the other biomarkers. CONCLUSIONS: Overweight/obese men with PCa undergoing AS who participated in a lifestyle-based weight loss intervention successfully met weight loss goals with this reproducible lifestyle intervention and experienced improvements in glucose-regulation biomarkers associated with PCa progression.

Isolating the Drivers of Racial Inequities in Prostate Cancer Treatment.

BACKGROUND: Black individuals in the United States are less likely than White individuals to receive curative therapies despite a 2-fold higher risk of prostate cancer death. While research has described treatment inequities, few studies have investigated underlying causes. METHODS: We analyzed a cohort of 40,137 Medicare beneficiaries (66 and older) linked to the Surveillance Epidemiology and End Results (SEER) cancer registry who had clinically significant, non-metastatic (cT1-4N0M0, grade group 2-5) prostate cancer (diagnosed 2010-2015). Using the Kitagawa-Oaxaca-Blinder decomposition, we assessed the contributions of patient health and health care delivery on the racial difference in localized prostate cancer treatments (radical prostatectomy or radiation). Patient health consisted of comorbid diagnoses, tumor characteristics, SEER site, diagnosis year, and age. Health care delivery was captured as a prediction model with these health variables as predictors of treatment, reflecting current treatment patterns. RESULTS: A total of 72.1% and 78.6% of Black and White patients received definitive treatment, respectively, a difference of 6.5 percentage points. An estimated 15% [95% confidence interval (CI): 6-24] of this treatment difference was explained by measured differences in patient health, leaving the remaining estimated 85% (95% CI: 74-94) attributable to a potentially broad range of health care delivery factors. Limitations included insufficient data to explore how specific health care delivery factors, including structural racism and social determinants, impact differential treatment. CONCLUSIONS: Our results show the inadequacy of patient health differences as an explanation of the treatment inequity. IMPACT: Investing in studies and interventions that support equitable health care delivery for Black individuals with prostate cancer will contribute to improved outcomes.

Revisiting the standard blueprint for biomarker development to address emerging cancer early detection technologies.

Novel liquid biopsy technologies are creating a watershed moment in cancer early detection. Evidence supporting population screening is nascent, but a rush to market the new tests is prompting cancer early detection researchers to revisit the standard blueprint that the Early Detection Research Network established to evaluate novel screening biomarkers. In this commentary, we review the Early Detection Research Network's Phases of Biomarker Development (PBD) for rigorous evaluation of novel early detection biomarkers and discuss both hazards and opportunities involved in expedited evaluation. According to the PBD, for a biomarker-based test to be considered for population screening, 1) test sensitivity in a prospective screening setting must be adequate, 2) the shift to early curable stages must be meaningful, and 3) any stage shift must translate into clinically significant mortality benefit. In the past, determining mortality benefit has required lengthy randomized screening trials, but interest is growing in expedited trial designs with shorter-term endpoints. Whether and how best to use such endpoints in a manner that retains the rigor of the PBD remains to be determined. We discuss how computational disease modeling can be harnessed to learn about screening impact and meet the needs of the moment.

Prostate cancer screening in African American men: a review of the evidence.

BACKGROUND: Prostate cancer is the most diagnosed cancer in African American men, yet prostate cancer screening regimens in this group are poorly guided by existing evidence, given underrepresentation of African American men in prostate cancer screening trials. It is critical to optimize prostate cancer screening and early detection in this high-risk group because underdiagnosis may lead to later-stage cancers at diagnosis and higher mortality while overdiagnosis may lead to unnecessary treatment. METHODS: We performed a review of the literature related to prostate cancer screening and early detection specific to African American men to summarize the existing evidence available to guide health-care practice. RESULTS: Limited evidence from observational and modeling studies suggests that African American men should be screened for prostate cancer. Consideration should be given to initiating screening of African American men at younger ages (eg, 45-50 years) and at more frequent intervals relative to other racial groups in the United States. Screening intervals can be optimized by using a baseline prostate-specific antigen measurement in midlife. Finally, no evidence has indicated that African American men would benefit from screening beyond 75 years of age; in fact, this group may experience higher rates of overdiagnosis at older ages. CONCLUSIONS: The evidence base for prostate cancer screening in African American men is limited by the lack of large, randomized studies. Our literature search supported the need for African American men to be screened for prostate cancer, for initiating screening at younger ages (45-50 years), and perhaps screening at more frequent intervals relative to men of other racial groups in the United States.

Screening for lung cancer: 2023 guideline update from the American Cancer Society.

Lung cancer is the leading cause of mortality and person-years of life lost from cancer among US men and women. Early detection has been shown to be associated with reduced lung cancer mortality. Our objective was to update the American Cancer Society (ACS) 2013 lung cancer screening (LCS) guideline for adults at high risk for lung cancer. The guideline is intended to provide guidance for screening to health care providers and their patients who are at high risk for lung cancer due to a history of smoking. The ACS Guideline Development Group (GDG) utilized a systematic review of the LCS literature commissioned for the US Preventive Services Task Force 2021 LCS recommendation update; a second systematic review of lung cancer risk associated with years since quitting smoking (YSQ); literature published since 2021; two Cancer Intervention and Surveillance Modeling Network-validated lung cancer models to assess the benefits and harms of screening; an epidemiologic and modeling analysis examining the effect of YSQ and aging on lung cancer risk; and an updated analysis of benefit-to-radiation-risk ratios from LCS and follow-up examinations. The GDG also examined disease burden data from the National Cancer Institute's Surveillance, Epidemiology, and End Results program. Formulation of recommendations was based on the quality of the evidence and judgment (incorporating values and preferences) about the balance of benefits and harms. The GDG judged that the overall evidence was moderate and sufficient to support a strong recommendation for screening individuals who meet the eligibility criteria. LCS in men and women aged 50-80 years is associated with a reduction in lung cancer deaths across a range of study designs, and inferential evidence supports LCS for men and women older than 80 years who are in good health. The ACS recommends annual LCS with low-dose computed tomography for asymptomatic individuals aged 50-80 years who currently smoke or formerly smoked and have a ≥20 pack-year smoking history (strong recommendation, moderate quality of evidence). Before the decision is made to initiate LCS, individuals should engage in a shared decision-making discussion with a qualified health professional. For individuals who formerly smoked, the number of YSQ is not an eligibility criterion to begin or to stop screening. Individuals who currently smoke should receive counseling to quit and be connected to cessation resources. Individuals with comorbid conditions that substantially limit life expectancy should not be screened. These recommendations should be considered by health care providers and adults at high risk for lung cancer in discussions about LCS. If fully implemented, these recommendations have a high likelihood of significantly reducing death and suffering from lung cancer in the United States.

Benefits and harms of prostate specific antigen testing according to Australian guidelines.

Guidelines for prostate specific antigen (PSA) testing in Australia recommend that men at average risk of prostate cancer who have been informed of the benefits and harms, and who decide to undergo regular testing, should be offered testing every 2 years from 50 to 69 years. This study aimed to estimate the benefits and harms of regular testing in this context. We constructed Policy1-Prostate, a discrete event microsimulation platform of the natural history of prostate cancer and prostate cancer survival, and PSA testing patterns and subsequent management in Australia. The model was calibrated to pre-PSA (before 1985) prostate cancer incidence and mortality and validated against incidence and mortality trends from 1985 to 2011 and international trials. The model predictions were concordant with trials and Australian observed incidence and mortality data from 1985 to 2011. Out of 1000 men who choose to test according to the guidelines, 36 [21-41] men will die from prostate cancer and 126 [119-133] men will be diagnosed with prostate cancer, compared with 50 [47-54] and 94 [90-98] men who do not test, respectively. During the 20 years of active PSA testing, 32.3% [25.6%-38.8%] of all PSA-test detected cancers are overdiagnosed cases that is, 30 [21-42] out of 94 [83-107] PSA-test detected cancers. Australian men choosing to test with PSA every two years from 50 to 69 will reduce their risk of ever dying from prostate cancer and incur a risk of overdiagnosis: for every man who avoids dying from prostate cancer, two will be overdiagnosed with prostate cancer between 50 and 69 years of age. Australian men, with health professionals, can use these results to inform decision-making about PSA testing.

Racial disparities in prostate cancer mortality: a model-based decomposition of contributing factors.

To investigate the relative contributions of natural history and clinical interventions to racial disparities in prostate cancer mortality in the United States, we extended a model that was previously calibrated to Surveillance, Epidemiology, and End Results (SEER) incidence rates for the general population and for Black men. The extended model integrated SEER data on curative treatment frequencies and cancer-specific survival. Starting with the model for all men, we replaced up to 9 components with corresponding components for Black men, projecting age-standardized mortality rates for ages 40-84 years at each step. Based on projections in 2019, the increased frequency of developing disease, more aggressive tumor features, and worse cancer-specific survival in Black men diagnosed at local-regional and distant stages explained 38%, 34%, 22%, and 8% of the modeled disparity in mortality. Our results point to intensified screening and improved care in Black men as priority areas to achieve greater equity.

Temporal effect of imatinib adherence on time to remission in chronic myeloid leukemia patients.

INTRODUCTION: Adherence to imatinib in chronic myeloid leukemia (CML) patients is estimated to be as low as 70% despite its clinical benefit, and our understanding of the impact of nonadherence in this population is limited. This study presents a novel application of the Alternating Conditional Estimation (ACE) algorithm in newly diagnosed CML patients to map the full dose-response curve (DRC) and determine how the strength of this curve varies over time. METHODS: We applied the ACE algorithm alongside a backward elimination procedure to detect the presence of time dependence and nonlinearity in the relationship between imatinib adherence and time-to-remission. An extended Cox model allowing for the flexible modeling of identified effects via unpenalized B-splines was subsequently fit and assessed. RESULTS: The substantial improvement in model fit associated with the extended Cox approach suggests that traditional Cox proportional hazards model assumptions do not hold in this setting. Results indicate that the DRC for imatinib is non-linearly increasing, with an attenuated effect above a 74% adherence rate. The strength of this effect on remission varied over time and was strongest in the initial months of treatment, reaching a peak around 90 days post-initiation (log hazard ratio: 2.12, 95% confidence interval: 1.47 to 2.66). CONCLUSION: Most patients that achieved remission did so by 4 months (120 days) with consistently high adherence, suggesting that this could be a critical time and duration for realizing treatment benefit and patient monitoring. Findings regarding the relationship between adherence and remission can additionally help guide the design of future studies.

Multicancer Early Detection Tests: An Overview of Early Results From Prospective Clinical Studies and Opportunities for Oncologists.

A multitude of blood-based multicancer early detection (MCED) tests assessing cancer-related alterations in circulating genomic analytes and other associated signatures are currently being developed with the potential to disrupt current single-organ screening paradigms. Pathways for clinical implementation of these novel MCED tests have not been delineated, particularly for the patients with signal positive results requiring additional confirmatory testing. In this overview, we highlight early results from prospective clinical studies testing the efficacy of genomic MCED tests in cohorts of patients without known cancer diagnoses. Additionally, we discuss a proposed professional expansion of the oncology practice relating to the diagnostic workup of individuals found to have an MCED signal positive for cancer. As MCED blood tests have the potential to dramatically upend current cancer screening paradigms and downstream cancer therapy, it is imperative for oncologists to be aware of important clinical studies and the multitude of unanswered questions. The current gaps in the clinical implication of these tests may serve as a meaningful and rewarding expansion of oncology practice.

Melanoma literacy among the general population of three western US states.

Melanoma is a significant cause of cancer death, despite being detectable without specialized or invasive technologies. Understanding barriers to preventive behaviors such as skin self-examination (SSE) could help to define interventions for increasing the frequency of early detection. To determine melanoma knowledge and beliefs across three high-incidence US states, 15,000 surveys were sent to a population-representative sample. We aimed to assess (1) melanoma literacy (i.e., knowledge about melanoma risks, attitudes, and preventive behaviors) and (2) self-reported SSE and its association with melanoma literacy, self-efficacy, and belief in the benefits of SSE. Of 2326 respondents, only 21.2% provided responses indicating high knowledge of melanoma, and 62.8% reported performing an SSE at any time in their lives. Only 38.3% and 7.3% reported being "fairly" or "very" confident about doing SSE, respectively. SSE performance among respondents was most strongly associated with higher melanoma knowledge, higher self-efficacy, and personal history of melanoma. Melanoma literacy among survey respondents was modest, with greater literacy associated with a higher likelihood of reported preventive behavior. This assessment establishes a baseline and provides guidance for public health campaigns designed to increase prevention and early detection of this lethal cancer.

Test sensitivity in a prospective cancer screening program: A critique of a common proxy measure.

The true sensitivity of a cancer screening test, defined as the frequency with which the test returns a positive result if the cancer is present, is a key indicator of diagnostic performance. Given the challenges of directly assessing test sensitivity in a prospective screening program, proxy measures for true sensitivity are frequently reported. We call one such proxy empirical sensitivity, as it is given by the observed ratio of screen-detected cancers to the sum of screen-detected and interval cancers. In the setting of the canonical three-state Markov model for progression from preclinical onset to clinical diagnosis, we formulate a mathematical relationship for how empirical sensitivity varies with the screening interval and the mean preclinical sojourn time and identify conditions under which empirical sensitivity exceeds or falls short of true sensitivity. In particular, when the inter-screening interval is short relative to the mean sojourn time, empirical sensitivity tends to exceed true sensitivity, unless true sensitivity is high. The Breast Cancer Surveillance Consortium (BCSC) has reported an estimate of 0.87 for the empirical sensitivity of digital mammography. We show that this corresponds to a true sensitivity of 0.82 under a mean sojourn time of 3.6 years estimated based on breast cancer screening trials. However, the BCSC estimate of empirical sensitivity corresponds to even lower true sensitivity under more contemporary, longer estimates of mean sojourn time. Consistently applied nomenclature that distinguishes empirical sensitivity from true sensitivity is needed to ensure that published estimates of sensitivity from prospective screening studies are properly interpreted.

Short-term Endpoints for Cancer Screening Trials: Does Tumor Subtype Matter?

Multicancer early detection tests are precipitating a reexamination of potential short-term endpoints for cancer screening trials. A reduction in advanced stage incidence is a prime candidate, and stage-shift models that substitute early-stage for late-stage survival have been used to predict mortality reduction due to screening. However, standard stage-shift models often ignore prognostic subtypes, effectively implying that cancers detected early also have an associated subtype shift. To illustrate the differences between mortality predictions from stage-shift models that ignore versus preserve prognostic subtype, we use ovarian cancer partitioned by histologic subtype and prostate cancer partitioned by grade. We infer general conditions under which stage-shift models that preserve prognostic subtype are likely to predict mortality reductions that differ from those that ignore subtype and examine the implications for short-term endpoints based on stage in cancer screening trials.

Risk of cancer versus risk of cancer diagnosis? Accounting for diagnostic bias in predictions of breast cancer risk by race and ethnicity.

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.