Jane Lange - Academia.edu (original) (raw)

Papers by Jane Lange

Cancer Research, Mar 1, 2023

JNCI: Journal of the National Cancer Institute, 2020

Background Studies conducted in Swedish populations have shown that men with lowest prostate-spec... more Background Studies conducted in Swedish populations have shown that men with lowest prostate-specific antigen (PSA) levels at ages 44–50 years and 60 years have very low risk of future distant metastasis or death from prostate cancer. This study investigates benefits and harms of screening strategies stratified by PSA levels. Methods PSA levels and diagnosis patterns from two microsimulation models of prostate cancer progression, detection, and mortality were compared against results of the Malmö Preventive Project, which stored serum and tracked subsequent prostate cancer diagnoses for 25 years. The models predicted the harms (tests and overdiagnoses) and benefits (lives saved and life-years gained) of PSA-stratified screening strategies compared with biennial screening from age 45 years to age 69 years. Results Compared with biennial screening for ages 45–69 years, lengthening screening intervals for men with PSA less than 1.0 ng/mL at age 45 years led to 46.8–47.0% fewer tests (r...

Statistics in Medicine, Jun 5, 2013

Multistate models are used to characterize disease processes within an individual. Clinical studi... more Multistate models are used to characterize disease processes within an individual. Clinical studies often observe the disease status of individuals at discrete time points, making exact times of transitions between disease states unknown. Such panel data pose considerable modeling challenges. Assuming the disease process progresses according a standard continuous-time Markov chain (CTMC) yields tractable likelihoods, but the assumption of exponential sojourn time distributions is typically unrealistic. More flexible semi-Markov models permit generic sojourn distributions yet yield intractable likelihoods for panel data in the presence of reversible transitions. One attractive alternative is to assume that the disease process is characterized by an underlying latent CTMC, with multiple latent states mapping to each disease state. These models retain analytic tractability due to the CTMC framework but allow for flexible, duration-dependent disease state sojourn distributions. We have developed a robust and efficient expectation-maximization (EM) algorithm in this context. Our complete data state space consists of the observed data and the underlying latent trajectory, yielding computationally efficient expectation and maximization steps. Our algorithm outperforms alternative methods measured in terms of time to convergence and robustness. We also examine the frequentist performance of latent CTMC point and interval estimates of disease process functionals based on simulated data. The performance of estimates depends on time, functional, and data-generating scenario. Finally, we illustrate the interpretive power of latent CTMC models for describing disease processes on a data-set of lung transplant patients. We hope our work will encourage wider use of these models in the biomedical setting.

Journal of Alternative and Complementary Medicine, Nov 1, 2016

Background: Patient expectations may be associated with outcomes of complementary and alternative... more Background: Patient expectations may be associated with outcomes of complementary and alternative medicine (CAM) treatments for chronic pain. However, a psychometrically sound measure of such expectations is needed. Objectives: The purpose of this study was to develop and evaluate a questionnaire to assess individuals' expectations regarding outcomes of CAM treatments for chronic low back pain (CLBP), as well as a short form of the questionnaire. Methods: An 18-item draft questionnaire was developed through literature review, cognitive interviews with individuals with CLBP, CAM practitioners, and expert consultation. Two samples completed the questionnaire: (1) a community sample (n = 141) completed it via an online survey before or soon after starting a CAM treatment for CLBP, and (2) participants (n = 181) in randomized clinical trials evaluating CAM treatments for CLBP or fibromyalgia completed it prior to or shortly after starting treatment. Factor structure, internal consistency, test-retest reliability, and criterion validity were examined. Results: Based on factor analyses, 10 items reflecting expectations (used to create a total score) and three items reflecting hopes (not scored) were selected for the questionnaire. The questionnaire had high internal consistency, moderate test-retest reliability, and moderate correlations with other measures of expectations. A three-item short form also had adequate reliability and validity. Conclusions: The Expectations for Complementary and Alternative Medicine Treatments (EXPECT) questionnaire can be used in research to assess individuals' expectations of treatments for chronic pain. It is recommended that the three hope questions are included (but not scored) to help respondents distinguish between hopes and expectations. The short form may be appropriate for clinical settings and when expectation measurement is not a primary focus.

Psychiatric Services, Oct 1, 2009

Objective-This study examined racial-ethnic differences in the impact of the Youth Partners in Ca... more Objective-This study examined racial-ethnic differences in the impact of the Youth Partners in Care quality improvement intervention. The intervention was designed to improve access to evidence-based depression care, primarily cognitive-behavioral therapy and medication, through primary care. Previous analyses have shown that the quality improvement intervention was associated with improved depression and quality-of-life outcomes at the end of the six-month intervention period. Methods-A randomized controlled trial comparing quality improvement and usual care for youths from diverse racial-ethnic groups from five health care organizations, including managed care, the public sector, and academic center clinics, was conducted. Depressed youths (N=325), who self-identified as black (N=59), Latino (N=224), and white (N=42), aged 13-21 years, were included in these analyses. To evaluate intervention effects within racial-ethnic groups, regression models were constructed, which adjusted for baseline and study site variation in depression symptoms, mental health status, satisfaction with mental health care, and mental health service utilization. Results-Differential intervention effects were found across racial-ethnic groups. Black youths in the intervention group experienced significant reductions in depression symptoms and had higher rates of use of specialty mental health care at the six-month follow-up. Among Latino youths, the intervention was associated with significantly greater satisfaction with care. Intervention effects were weak among white youths. Conclusions-Quality improvement interventions may help to reduce disparities in mental health care for youths from racial-ethnic minority groups. Racial-ethnic diversity among children in the United States is increasing. In 2000 children from minority groups accounted for 39% of the population under 18 (1), and the proportion is projected to rise to 48% in the next quarter century (2). Increasingly, evidence-based mental health interventions have been found effective for youths from ethnic minority groups (3,4). Nevertheless, these children are less likely than white youths to receive high-Dr. Asarnow has provided consultation on CBT supported by an unrestricted grant from Pfizer and has received unrestricted research funding from Philip Morris.

Cancer, Oct 27, 2014

Background-Standard treatment of pulmonary metastasis in patients with Wilms tumor (WT) includes ... more Background-Standard treatment of pulmonary metastasis in patients with Wilms tumor (WT) includes 12 Gy radiation therapy (RT) to the entire chest. The risk of breast cancer (BC) in a large cohort of female survivors of WT has not previously been reported. Methods-2,492 female participants in National Wilms Tumor Studies 1-4 (1969-1995) were followed from age 15 through mid 2013 for incident BC. Median age at last contact was 27.3 years. We calculated cumulative risk at age 40 (CR40), hazard ratios (HR) by Cox regression, standardized incidence ratios (SIR) relative to US population rates and [shown in brackets] 95% confidence intervals. Results-Numbers of survivors with invasive BC divided by numbers at risk were 16/369 (CR40=14.8% [8.7-24.5]) for women who received chest RT for metastatic WT, 10/894 (CR40=3.1% [1.3-7.41]) for those who received only abdominal RT and 2/1,229 (CR40=0.3% [0.0-2.3]) for those who received no RT. The SIRs for these three groups were 27.6 [16.1-44.2] based on 5,010 person-years (PY) of follow-up, 6.0 [2.9,11.0] based on 13,185 PY, and 2.2 [0.3,7.8] based on 13,560 PY, respectively. The risk was high regardless of chest RT among women diagnosed with WT at age 10 or later, with 9/90 developing BC (CR40=13.5% [5.6-30.6], SIR=23.6 [10.8-44.8], PY=1,463). Conclusion-Female WT survivors treated with chest RT had high risk of early BC, with nearly 15% developing invasive disease by age 40. Current guidelines that recommend screening only survivors receiving ≥20 Gy RT to the chest might be re-evaluated.

JAMA Oncology, 2017

Background-Atypical ductal hyperplasia (ADH) is a known strong risk factor for breast cancer. Pub... more Background-Atypical ductal hyperplasia (ADH) is a known strong risk factor for breast cancer. Published risk estimates are based on cohorts that included women diagnosed prior to the widespread use of screening mammograms and do not differentiate between the methods used to diagnose ADH, which may be related to size of the ADH focus. These risks may overestimate the risk of women currently diagnosed with ADH. We sought to examine the risk of invasive cancer associated with ADH diagnosed on core needle biopsy versus excisional biopsy. Design-Cohort study comparing ten-year cumulative risk of invasive breast cancer in women undergoing mammography with and without a diagnosis of ADH. Setting-Five breast imaging registries that participate in the National Cancer Institute-funded Breast Cancer Surveillance Consortium (BCSC). Participants-Women undergoing mammography in the BCSC. Exposure-Diagnosis of ADH on core needle biopsy or excisional biopsy in women undergoing mammography. Main outcome-Ten-year cumulative risk of invasive breast cancer risk.

Annals of Internal Medicine, Jan 12, 2016

Background-Estimates of radiation-induced breast cancer risk from mammography screening have not ... more Background-Estimates of radiation-induced breast cancer risk from mammography screening have not previously considered dose exposure variation or diagnostic work-up after abnormal screening. Objective-To estimate distributions of radiation-induced breast cancer incidence and mortality from digital mammography screening, considering exposure from screening and diagnostic mammography and dose variation across women. Design-Two simulation-modeling approaches using common data on screening mammography from the Breast Cancer Surveillance Consortium and radiation dose from mammography from the Digital Mammographic Imaging Screening Trial. Setting-U.S. population. Patients-Women aged 40-74 years. Interventions-Annual or biennial digital mammography screening from age 40, 45, or 50 until 74. Measurements-Lifetime breast cancer deaths averted (benefits) and radiation-induced breast cancer incidence and mortality per 100,000 women screened (harms). Results-On average, annual screening of 100,000 women aged 40 to 74 years was projected to induce 125 breast cancers (95% confidence interval [CI]=88-178) leading to 16 deaths (95% CI=11-23) relative to 968 breast cancer deaths averted by early detection from screening. Women exposed at the 95 th percentile were projected to develop 246 radiation-induced breast cancers leading to 32 deaths per 100,000 women. Women with large breasts requiring extra views for complete breast examination (8% of population) were projected to have higher radiation-induced breast cancer incidence and mortality (266 cancers, 35 deaths per 100,000 women), compared to women with small or average breasts (113 cancers, 15 deaths per 100,000 women). Biennial screening starting at age 50 reduced risk of radiation-induced cancers 5-fold. Limitations-We were unable to estimate years of life lost from radiation-induced breast cancer. Conclusions-Radiation-induced breast cancer incidence and mortality from digital mammography screening are impacted by dose variability from screening and resultant diagnostic work-up, initiation age, and screening frequency. Women with large breasts may be at higher risk of radiation-induced breast cancer; however, the benefits of screening outweigh these risks.

Journal of Medical Screening

Objectives Cancer risk prediction may be subject to detection bias if utilization of screening is... more 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...

Journal of Medical Screening

Objectives When evaluating potential new cancer screening modalities, estimating sensitivity, esp... more Objectives When evaluating potential new cancer screening modalities, estimating sensitivity, especially for early-stage cases, is critical. There are methods to approximate stage-specific sensitivity in asymptomatic populations, both in the prospective (active screening) and retrospective (stored specimens) scenarios. We explored their validity via a simulation study. Methods We fit natural history models to lung and ovarian cancer screening data that permitted estimation of stage-specific (early/late) true sensitivity, defined as the probability subjects screened in the given stage had positive tests. We then ran simulations, using the fitted models, of the prospective and retrospective scenarios. Prospective sensitivity by stage was estimated as screen-detected divided by screen-plus interval-detected cancers, where stage is defined as stage at detection. Retrospective sensitivity by stage was estimated based on cancers detected within specified windows before clinical diagnosis ...

Cancer Prevention Research

Early detection cannot succeed unless there is adequate opportunity for cancer to be diagnosed an... more Early detection cannot succeed unless there is adequate opportunity for cancer to be diagnosed and intercepted within its early preclinical phase. An understanding of opportunity for early detection and interception is therefore critical in predicting potential mortality reduction due to screening. Opportunity is not directly observable but may be learned using data from prospectively screened cohorts and populations. In this presentation I will share a history of methods for learning about early detection opportunity and will present examples of how we have built on this work to study opportunity for early detection in prostate and breast cancer. I will describe a generic model of how opportunity and sensitivity combine to produce stage shift and mortality reduction and will briefly explore whether a lack of opportunity may have been behind the results of the UCKCTOCS trial. I will use this learning to motivate why I believe a prospective study to investigate opportunity for multi-...

JAMA Health Forum

IMPORTANCE The benefit of prostate-specific antigen screening may be greatest in high-risk popula... more IMPORTANCE The benefit of prostate-specific antigen screening may be greatest in high-risk populations, including men of African descent in the Caribbean. However, organized screening may not be sustainable in low-and middle-income countries. OBJECTIVE To evaluate the expected population outcomes and resource use of conservative prostate-specific antigen screening programs in the Bahamas. DESIGN, SETTING, AND PARTICIPANTS Prostate cancer incidence from GLOBOCAN and prostatespecific antigen screening data for 4300 men from the Bahamas were used to recalibrate 2 decision analytical models previously used to study prostate-specific antigen screening for Black men in the United States. Data on age and results obtained from prostate-specific antigen screening tests

Statistics in medicine, Jan 30, 2016

Diagnostic evaluation of suspected breast cancer due to abnormal screening mammography results is... more Diagnostic evaluation of suspected breast cancer due to abnormal screening mammography results is common, creates anxiety for women and is costly for the healthcare system. Timely evaluation with minimal use of additional diagnostic testing is key to minimizing anxiety and cost. In this paper, we propose a Bayesian semi-Markov model that allows for flexible, semi-parametric specification of the sojourn time distributions and apply our model to an investigation of the process of diagnostic evaluation with mammography, ultrasound and biopsy following an abnormal screening mammogram. We also investigate risk factors associated with the sojourn time between diagnostic tests. By utilizing semi-Markov processes, we expand on prior work that described the timing of the first test received by providing additional information such as the mean time to resolution and proportion of women with unresolved mammograms after 90 days for women requiring different sequences of tests in order to reach ...

Journal of Women's Health, 2009

Purpose: To examine perceived need for care for mental health problems as a possible contributor ... more Purpose: To examine perceived need for care for mental health problems as a possible contributor to ethnic disparities in receiving care among low-income depressed women. Methods: The role of ethnicity, somatization, and stigma as they relate to perceived need for care is examined. Participants were 1577 low-income women who met criteria for depression. Results: Compared with U.S.-born depressed white women, most depressed ethnic minority women were less likely to perceive a need for mental health care (black immigrants: OR 0.30, p < 0.001; U.S.-born blacks: OR 0.43, p < 0.001; immigrant Latinas: OR 0.52, p < 0.01). Stigma-related concerns decreased the likelihood of perceiving a need for mental health care (OR 0.80, p < 0.05). Having multiple somatic symptoms (OR 1.57, p < 0.001) increased the likelihood of endorsing perceived need. Conclusions: Findings suggest that there are ethnic differences in perceived need for mental healthcare that may partially account for the low rates of care for depression among low-income and minority women. The relations among stigma, somatization, and perceived need were strikingly similar across ethnic groups.

Latent Continuous Time Markov Chains for Partially-Observed Multistate Disease Processes

Cancer Epidemiology, Biomarkers & Prevention

Cancer modeling has become an accepted method for generating evidence about comparative effective... more Cancer modeling has become an accepted method for generating evidence about comparative effectiveness and cost-effectiveness of candidate cancer control policies across the continuum of care. Models of early detection policies require inputs concerning disease natural history and screening test performance, which are often subject to considerable uncertainty. Model validation against an external data source can increase confidence in the reliability of assumed or calibrated inputs. When a model fails to validate, this presents an opportunity to revise these inputs, thereby learning new information about disease natural history or diagnostic performance that could both enhance the model results and inform real-world practices. We discuss the conditions necessary for validly drawing conclusions about specific inputs such as diagnostic performance from model validation studies. Doing so requires being able to faithfully replicate the validation study in terms of its design and implemen...

Evaluation & the Health Professions

In studies of cancer risk, detection bias arises when risk factors are associated with screening ... more In studies of cancer risk, detection bias arises when risk factors are associated with screening patterns, affecting the likelihood and timing of diagnosis. To eliminate detection bias in a screened cohort, we propose modeling the latent onset of cancer and estimating the association between risk factors and onset rather than diagnosis. We apply this framework to estimate the increase in prostate cancer risk associated with black race and family history using data from the SELECT prostate cancer prevention trial, in which men were screened and biopsied according to community practices. A positive family history was associated with a hazard ratio (HR) of prostate cancer onset of 1.8, lower than the corresponding HR of prostate cancer diagnosis (HR = 2.2). This result comports with a finding that men in SELECT with a family history were more likely to be biopsied following a positive PSA test than men with no family history. For black race, the HRs for onset and diagnosis were similar...

Cancer Research, 2022

Background. Breast cancer screening is subject to overdiagnosis, that is the mammographic detecti... more Background. Breast cancer screening is subject to overdiagnosis, that is the mammographic detection of cancers that would not become symptomatic or otherwise cause harm in the absence of screening. The risk of overdiagnosis associated with screening mammography is a concern but there is no consensus about its magnitude. Estimates based on excess incidence are prone to bias, and estimates based on models have been criticized for not explicitly accommodating indolent tumors. Methods. We obtained individual mammography screening and breast cancer diagnosis records from the Breast Cancer Surveillance Consortium (BCSC), an authoritative data source in the US. Women aged 50-74 years who had their first mammogram in the BCSC between 2000-2018 were included. We fit a mathematical model that accounts for the transition from healthy to preclinical and clinical disease while allowing for a fraction of indolent preclinical tumors. We performed Bayesian inference using the Hamiltonian Monte Carl...

Annals of Internal Medicine, 2022

Cancer Research, Mar 1, 2023

JNCI: Journal of the National Cancer Institute, 2020

Background Studies conducted in Swedish populations have shown that men with lowest prostate-spec... more Background Studies conducted in Swedish populations have shown that men with lowest prostate-specific antigen (PSA) levels at ages 44–50 years and 60 years have very low risk of future distant metastasis or death from prostate cancer. This study investigates benefits and harms of screening strategies stratified by PSA levels. Methods PSA levels and diagnosis patterns from two microsimulation models of prostate cancer progression, detection, and mortality were compared against results of the Malmö Preventive Project, which stored serum and tracked subsequent prostate cancer diagnoses for 25 years. The models predicted the harms (tests and overdiagnoses) and benefits (lives saved and life-years gained) of PSA-stratified screening strategies compared with biennial screening from age 45 years to age 69 years. Results Compared with biennial screening for ages 45–69 years, lengthening screening intervals for men with PSA less than 1.0 ng/mL at age 45 years led to 46.8–47.0% fewer tests (r...

Statistics in Medicine, Jun 5, 2013

Multistate models are used to characterize disease processes within an individual. Clinical studi... more Multistate models are used to characterize disease processes within an individual. Clinical studies often observe the disease status of individuals at discrete time points, making exact times of transitions between disease states unknown. Such panel data pose considerable modeling challenges. Assuming the disease process progresses according a standard continuous-time Markov chain (CTMC) yields tractable likelihoods, but the assumption of exponential sojourn time distributions is typically unrealistic. More flexible semi-Markov models permit generic sojourn distributions yet yield intractable likelihoods for panel data in the presence of reversible transitions. One attractive alternative is to assume that the disease process is characterized by an underlying latent CTMC, with multiple latent states mapping to each disease state. These models retain analytic tractability due to the CTMC framework but allow for flexible, duration-dependent disease state sojourn distributions. We have developed a robust and efficient expectation-maximization (EM) algorithm in this context. Our complete data state space consists of the observed data and the underlying latent trajectory, yielding computationally efficient expectation and maximization steps. Our algorithm outperforms alternative methods measured in terms of time to convergence and robustness. We also examine the frequentist performance of latent CTMC point and interval estimates of disease process functionals based on simulated data. The performance of estimates depends on time, functional, and data-generating scenario. Finally, we illustrate the interpretive power of latent CTMC models for describing disease processes on a data-set of lung transplant patients. We hope our work will encourage wider use of these models in the biomedical setting.

Journal of Alternative and Complementary Medicine, Nov 1, 2016

Background: Patient expectations may be associated with outcomes of complementary and alternative... more Background: Patient expectations may be associated with outcomes of complementary and alternative medicine (CAM) treatments for chronic pain. However, a psychometrically sound measure of such expectations is needed. Objectives: The purpose of this study was to develop and evaluate a questionnaire to assess individuals' expectations regarding outcomes of CAM treatments for chronic low back pain (CLBP), as well as a short form of the questionnaire. Methods: An 18-item draft questionnaire was developed through literature review, cognitive interviews with individuals with CLBP, CAM practitioners, and expert consultation. Two samples completed the questionnaire: (1) a community sample (n = 141) completed it via an online survey before or soon after starting a CAM treatment for CLBP, and (2) participants (n = 181) in randomized clinical trials evaluating CAM treatments for CLBP or fibromyalgia completed it prior to or shortly after starting treatment. Factor structure, internal consistency, test-retest reliability, and criterion validity were examined. Results: Based on factor analyses, 10 items reflecting expectations (used to create a total score) and three items reflecting hopes (not scored) were selected for the questionnaire. The questionnaire had high internal consistency, moderate test-retest reliability, and moderate correlations with other measures of expectations. A three-item short form also had adequate reliability and validity. Conclusions: The Expectations for Complementary and Alternative Medicine Treatments (EXPECT) questionnaire can be used in research to assess individuals' expectations of treatments for chronic pain. It is recommended that the three hope questions are included (but not scored) to help respondents distinguish between hopes and expectations. The short form may be appropriate for clinical settings and when expectation measurement is not a primary focus.

Psychiatric Services, Oct 1, 2009

Objective-This study examined racial-ethnic differences in the impact of the Youth Partners in Ca... more Objective-This study examined racial-ethnic differences in the impact of the Youth Partners in Care quality improvement intervention. The intervention was designed to improve access to evidence-based depression care, primarily cognitive-behavioral therapy and medication, through primary care. Previous analyses have shown that the quality improvement intervention was associated with improved depression and quality-of-life outcomes at the end of the six-month intervention period. Methods-A randomized controlled trial comparing quality improvement and usual care for youths from diverse racial-ethnic groups from five health care organizations, including managed care, the public sector, and academic center clinics, was conducted. Depressed youths (N=325), who self-identified as black (N=59), Latino (N=224), and white (N=42), aged 13-21 years, were included in these analyses. To evaluate intervention effects within racial-ethnic groups, regression models were constructed, which adjusted for baseline and study site variation in depression symptoms, mental health status, satisfaction with mental health care, and mental health service utilization. Results-Differential intervention effects were found across racial-ethnic groups. Black youths in the intervention group experienced significant reductions in depression symptoms and had higher rates of use of specialty mental health care at the six-month follow-up. Among Latino youths, the intervention was associated with significantly greater satisfaction with care. Intervention effects were weak among white youths. Conclusions-Quality improvement interventions may help to reduce disparities in mental health care for youths from racial-ethnic minority groups. Racial-ethnic diversity among children in the United States is increasing. In 2000 children from minority groups accounted for 39% of the population under 18 (1), and the proportion is projected to rise to 48% in the next quarter century (2). Increasingly, evidence-based mental health interventions have been found effective for youths from ethnic minority groups (3,4). Nevertheless, these children are less likely than white youths to receive high-Dr. Asarnow has provided consultation on CBT supported by an unrestricted grant from Pfizer and has received unrestricted research funding from Philip Morris.

Cancer, Oct 27, 2014

Background-Standard treatment of pulmonary metastasis in patients with Wilms tumor (WT) includes ... more Background-Standard treatment of pulmonary metastasis in patients with Wilms tumor (WT) includes 12 Gy radiation therapy (RT) to the entire chest. The risk of breast cancer (BC) in a large cohort of female survivors of WT has not previously been reported. Methods-2,492 female participants in National Wilms Tumor Studies 1-4 (1969-1995) were followed from age 15 through mid 2013 for incident BC. Median age at last contact was 27.3 years. We calculated cumulative risk at age 40 (CR40), hazard ratios (HR) by Cox regression, standardized incidence ratios (SIR) relative to US population rates and [shown in brackets] 95% confidence intervals. Results-Numbers of survivors with invasive BC divided by numbers at risk were 16/369 (CR40=14.8% [8.7-24.5]) for women who received chest RT for metastatic WT, 10/894 (CR40=3.1% [1.3-7.41]) for those who received only abdominal RT and 2/1,229 (CR40=0.3% [0.0-2.3]) for those who received no RT. The SIRs for these three groups were 27.6 [16.1-44.2] based on 5,010 person-years (PY) of follow-up, 6.0 [2.9,11.0] based on 13,185 PY, and 2.2 [0.3,7.8] based on 13,560 PY, respectively. The risk was high regardless of chest RT among women diagnosed with WT at age 10 or later, with 9/90 developing BC (CR40=13.5% [5.6-30.6], SIR=23.6 [10.8-44.8], PY=1,463). Conclusion-Female WT survivors treated with chest RT had high risk of early BC, with nearly 15% developing invasive disease by age 40. Current guidelines that recommend screening only survivors receiving ≥20 Gy RT to the chest might be re-evaluated.

JAMA Oncology, 2017

Background-Atypical ductal hyperplasia (ADH) is a known strong risk factor for breast cancer. Pub... more Background-Atypical ductal hyperplasia (ADH) is a known strong risk factor for breast cancer. Published risk estimates are based on cohorts that included women diagnosed prior to the widespread use of screening mammograms and do not differentiate between the methods used to diagnose ADH, which may be related to size of the ADH focus. These risks may overestimate the risk of women currently diagnosed with ADH. We sought to examine the risk of invasive cancer associated with ADH diagnosed on core needle biopsy versus excisional biopsy. Design-Cohort study comparing ten-year cumulative risk of invasive breast cancer in women undergoing mammography with and without a diagnosis of ADH. Setting-Five breast imaging registries that participate in the National Cancer Institute-funded Breast Cancer Surveillance Consortium (BCSC). Participants-Women undergoing mammography in the BCSC. Exposure-Diagnosis of ADH on core needle biopsy or excisional biopsy in women undergoing mammography. Main outcome-Ten-year cumulative risk of invasive breast cancer risk.

Annals of Internal Medicine, Jan 12, 2016

Background-Estimates of radiation-induced breast cancer risk from mammography screening have not ... more Background-Estimates of radiation-induced breast cancer risk from mammography screening have not previously considered dose exposure variation or diagnostic work-up after abnormal screening. Objective-To estimate distributions of radiation-induced breast cancer incidence and mortality from digital mammography screening, considering exposure from screening and diagnostic mammography and dose variation across women. Design-Two simulation-modeling approaches using common data on screening mammography from the Breast Cancer Surveillance Consortium and radiation dose from mammography from the Digital Mammographic Imaging Screening Trial. Setting-U.S. population. Patients-Women aged 40-74 years. Interventions-Annual or biennial digital mammography screening from age 40, 45, or 50 until 74. Measurements-Lifetime breast cancer deaths averted (benefits) and radiation-induced breast cancer incidence and mortality per 100,000 women screened (harms). Results-On average, annual screening of 100,000 women aged 40 to 74 years was projected to induce 125 breast cancers (95% confidence interval [CI]=88-178) leading to 16 deaths (95% CI=11-23) relative to 968 breast cancer deaths averted by early detection from screening. Women exposed at the 95 th percentile were projected to develop 246 radiation-induced breast cancers leading to 32 deaths per 100,000 women. Women with large breasts requiring extra views for complete breast examination (8% of population) were projected to have higher radiation-induced breast cancer incidence and mortality (266 cancers, 35 deaths per 100,000 women), compared to women with small or average breasts (113 cancers, 15 deaths per 100,000 women). Biennial screening starting at age 50 reduced risk of radiation-induced cancers 5-fold. Limitations-We were unable to estimate years of life lost from radiation-induced breast cancer. Conclusions-Radiation-induced breast cancer incidence and mortality from digital mammography screening are impacted by dose variability from screening and resultant diagnostic work-up, initiation age, and screening frequency. Women with large breasts may be at higher risk of radiation-induced breast cancer; however, the benefits of screening outweigh these risks.

Journal of Medical Screening

Objectives Cancer risk prediction may be subject to detection bias if utilization of screening is... more 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...

Journal of Medical Screening

Objectives When evaluating potential new cancer screening modalities, estimating sensitivity, esp... more Objectives When evaluating potential new cancer screening modalities, estimating sensitivity, especially for early-stage cases, is critical. There are methods to approximate stage-specific sensitivity in asymptomatic populations, both in the prospective (active screening) and retrospective (stored specimens) scenarios. We explored their validity via a simulation study. Methods We fit natural history models to lung and ovarian cancer screening data that permitted estimation of stage-specific (early/late) true sensitivity, defined as the probability subjects screened in the given stage had positive tests. We then ran simulations, using the fitted models, of the prospective and retrospective scenarios. Prospective sensitivity by stage was estimated as screen-detected divided by screen-plus interval-detected cancers, where stage is defined as stage at detection. Retrospective sensitivity by stage was estimated based on cancers detected within specified windows before clinical diagnosis ...

Cancer Prevention Research

Early detection cannot succeed unless there is adequate opportunity for cancer to be diagnosed an... more Early detection cannot succeed unless there is adequate opportunity for cancer to be diagnosed and intercepted within its early preclinical phase. An understanding of opportunity for early detection and interception is therefore critical in predicting potential mortality reduction due to screening. Opportunity is not directly observable but may be learned using data from prospectively screened cohorts and populations. In this presentation I will share a history of methods for learning about early detection opportunity and will present examples of how we have built on this work to study opportunity for early detection in prostate and breast cancer. I will describe a generic model of how opportunity and sensitivity combine to produce stage shift and mortality reduction and will briefly explore whether a lack of opportunity may have been behind the results of the UCKCTOCS trial. I will use this learning to motivate why I believe a prospective study to investigate opportunity for multi-...

JAMA Health Forum

IMPORTANCE The benefit of prostate-specific antigen screening may be greatest in high-risk popula... more IMPORTANCE The benefit of prostate-specific antigen screening may be greatest in high-risk populations, including men of African descent in the Caribbean. However, organized screening may not be sustainable in low-and middle-income countries. OBJECTIVE To evaluate the expected population outcomes and resource use of conservative prostate-specific antigen screening programs in the Bahamas. DESIGN, SETTING, AND PARTICIPANTS Prostate cancer incidence from GLOBOCAN and prostatespecific antigen screening data for 4300 men from the Bahamas were used to recalibrate 2 decision analytical models previously used to study prostate-specific antigen screening for Black men in the United States. Data on age and results obtained from prostate-specific antigen screening tests

Statistics in medicine, Jan 30, 2016

Diagnostic evaluation of suspected breast cancer due to abnormal screening mammography results is... more Diagnostic evaluation of suspected breast cancer due to abnormal screening mammography results is common, creates anxiety for women and is costly for the healthcare system. Timely evaluation with minimal use of additional diagnostic testing is key to minimizing anxiety and cost. In this paper, we propose a Bayesian semi-Markov model that allows for flexible, semi-parametric specification of the sojourn time distributions and apply our model to an investigation of the process of diagnostic evaluation with mammography, ultrasound and biopsy following an abnormal screening mammogram. We also investigate risk factors associated with the sojourn time between diagnostic tests. By utilizing semi-Markov processes, we expand on prior work that described the timing of the first test received by providing additional information such as the mean time to resolution and proportion of women with unresolved mammograms after 90 days for women requiring different sequences of tests in order to reach ...

Journal of Women's Health, 2009

Purpose: To examine perceived need for care for mental health problems as a possible contributor ... more Purpose: To examine perceived need for care for mental health problems as a possible contributor to ethnic disparities in receiving care among low-income depressed women. Methods: The role of ethnicity, somatization, and stigma as they relate to perceived need for care is examined. Participants were 1577 low-income women who met criteria for depression. Results: Compared with U.S.-born depressed white women, most depressed ethnic minority women were less likely to perceive a need for mental health care (black immigrants: OR 0.30, p < 0.001; U.S.-born blacks: OR 0.43, p < 0.001; immigrant Latinas: OR 0.52, p < 0.01). Stigma-related concerns decreased the likelihood of perceiving a need for mental health care (OR 0.80, p < 0.05). Having multiple somatic symptoms (OR 1.57, p < 0.001) increased the likelihood of endorsing perceived need. Conclusions: Findings suggest that there are ethnic differences in perceived need for mental healthcare that may partially account for the low rates of care for depression among low-income and minority women. The relations among stigma, somatization, and perceived need were strikingly similar across ethnic groups.

Latent Continuous Time Markov Chains for Partially-Observed Multistate Disease Processes

Cancer Epidemiology, Biomarkers & Prevention

Cancer modeling has become an accepted method for generating evidence about comparative effective... more Cancer modeling has become an accepted method for generating evidence about comparative effectiveness and cost-effectiveness of candidate cancer control policies across the continuum of care. Models of early detection policies require inputs concerning disease natural history and screening test performance, which are often subject to considerable uncertainty. Model validation against an external data source can increase confidence in the reliability of assumed or calibrated inputs. When a model fails to validate, this presents an opportunity to revise these inputs, thereby learning new information about disease natural history or diagnostic performance that could both enhance the model results and inform real-world practices. We discuss the conditions necessary for validly drawing conclusions about specific inputs such as diagnostic performance from model validation studies. Doing so requires being able to faithfully replicate the validation study in terms of its design and implemen...

Evaluation & the Health Professions

In studies of cancer risk, detection bias arises when risk factors are associated with screening ... more In studies of cancer risk, detection bias arises when risk factors are associated with screening patterns, affecting the likelihood and timing of diagnosis. To eliminate detection bias in a screened cohort, we propose modeling the latent onset of cancer and estimating the association between risk factors and onset rather than diagnosis. We apply this framework to estimate the increase in prostate cancer risk associated with black race and family history using data from the SELECT prostate cancer prevention trial, in which men were screened and biopsied according to community practices. A positive family history was associated with a hazard ratio (HR) of prostate cancer onset of 1.8, lower than the corresponding HR of prostate cancer diagnosis (HR = 2.2). This result comports with a finding that men in SELECT with a family history were more likely to be biopsied following a positive PSA test than men with no family history. For black race, the HRs for onset and diagnosis were similar...

Cancer Research, 2022

Background. Breast cancer screening is subject to overdiagnosis, that is the mammographic detecti... more Background. Breast cancer screening is subject to overdiagnosis, that is the mammographic detection of cancers that would not become symptomatic or otherwise cause harm in the absence of screening. The risk of overdiagnosis associated with screening mammography is a concern but there is no consensus about its magnitude. Estimates based on excess incidence are prone to bias, and estimates based on models have been criticized for not explicitly accommodating indolent tumors. Methods. We obtained individual mammography screening and breast cancer diagnosis records from the Breast Cancer Surveillance Consortium (BCSC), an authoritative data source in the US. Women aged 50-74 years who had their first mammogram in the BCSC between 2000-2018 were included. We fit a mathematical model that accounts for the transition from healthy to preclinical and clinical disease while allowing for a fraction of indolent preclinical tumors. We performed Bayesian inference using the Hamiltonian Monte Carl...

Annals of Internal Medicine, 2022