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Estimating the frequency of indolent breast cancer in screening trials.

ABSTRACT: Cancer screening can detect cancer that would not have been detected in a patient's lifetime without screening. Standard methods for analyzing screening data do not explicitly account for the possibility that a fraction of tumors may remain latent indefinitely. We extend these methods by representing cancers as a mixture of those that progress to symptoms (progressive) and those that remain latent (indolent). Given sensitivity of the screening test, we derive likelihood expressions to simultaneously estimate (1) the rate of onset of preclinical cancer, (2) the average preclinical duration of progressive cancers, and (3) the fraction of preclinical cancers that are indolent. Simulations demonstrate satisfactory performance of the estimation approach to identify model parameters subject to precise specifications of input parameters and adequate numbers of interval cancers. In application to four breast cancer screening trials, the estimated indolent fraction among preclinical cancers varies between 2% and 35% when assuming 80% test sensitivity and varying specifications for the earliest time that participants could plausibly have developed cancer. We conclude that standard methods for analyzing screening data can be extended to allow some indolent cancers, but accurate estimation depends on correctly specifying key inputs that may be difficult to determine precisely in practice.

SUBMITTER: Shen Y

PROVIDER: S-EPMC6027608 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Estimating the frequency of indolent breast cancer in screening trials.

Shen Yu Y Dong Wenli W Gulati Roman R Ryser Marc D MD Etzioni Ruth R

Statistical methods in medical research 20180205 4

Cancer screening can detect cancer that would not have been detected in a patient's lifetime without screening. Standard methods for analyzing screening data do not explicitly account for the possibility that a fraction of tumors may remain latent indefinitely. We extend these methods by representing cancers as a mixture of those that progress to symptoms (progressive) and those that remain latent (indolent). Given sensitivity of the screening test, we derive likelihood expressions to simultaneo ...[more]

PMID: 29402176

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Project description:BackgroundWe evaluate the construct validity of a proposed procedure for eliciting lay preferences among health care policy options, suited for structured surveys. It is illustrated with breast cancer screening, a domain in which people may have heterogeneous preferences.MethodsOur procedure applies behavioral decision research principles to eliciting preferences among policy options expressed in quantitative terms. Three-hundred women older than 18 y without a history of breast cancer were recruited through Amazon MTurk. Participants evaluated 4 screening options for each of 4 groups of women, with varying risk of breast cancer. Each option was characterized by estimates of 3 primary outcomes: breast cancer deaths, false alarms, and overdiagnosis resulting in unnecessary treatment of cancers that would not progress. These estimates were based on those currently being developed by the Breast Cancer Surveillance Consortium. For each risk group, participants stated how frequently they would wish to receive screening, if the predicted outcomes applied to them.ResultsA preregistered test found that preferences were robust enough to be unaffected by the order of introducing and displaying the outcomes. Other tests of construct validity also suggested that respondents generally understood the task and expressed consistent preferences. Those preferences were related to participants' age and mammography history but not to measures of their numeracy, subjective numeracy, or demographics. There was considerable heterogeneity in their preferences.ConclusionsMembers of the public can be engaged more fully in informing future screening guidelines if they evaluate the screening options characterized by the expected health outcomes expressed in quantitative terms. We offer and evaluate such a procedure, in terms of its construct validity with a diverse sample of women.HighlightsA novel survey method for eliciting lay preferences for breast cancer screening is proposed and evaluated in terms of its construct validity.Participants were generally insensitive to irrelevant task features (e.g., order of presentation) and sensitive to relevant ones (e.g., quantitative estimates of breast cancer risk, harms from screening).The proposed method elicits lay preferences in terms that can inform future screening guidelines, potentially improving communication between the public and policy makers.

Project description:In Germany, it is currently recommended that women start mammographic breast cancer screening at age 50. However, recently updated guidelines state that for women younger than 50 and older than 70 years of age, screening decisions should be based on individual risk. International clinical guidelines recommend starting screening when a woman's 5-year risk of breast cancer exceeds 1.7%. We thus compared the performance of the current age-based screening practice with an alternative risk-adapted approach using data from a German population representative survey. We found that 10,498,000 German women ages 50-69 years are eligible for mammographic screening based on age alone. Applying the 5-year risk threshold of 1.7% to individual breast cancer risk estimated from a model that considers a woman's reproductive and personal characteristics, 39,000 German women ages 40-49 years would additionally be eligible. Among those women, the number needed to screen to detect one breast cancer case, NNS, was 282, which was close to the NNS = 292 among all 50- to 69-year-old women. In contrast, NNS = 703 for the 113,000 German women ages 50-69 years old with 5-year breast cancer risk <0.8%, the median 5-year breast cancer risk for German women ages 45-49 years, which we used as a low-risk threshold. For these low-risk women, longer screening intervals might be considered to avoid unnecessary diagnostic procedures. In conclusion, we show that risk-adapted mammographic screening could benefit German women ages 40-49 years who are at elevated breast cancer risk and reduce cost and burden among low-risk women ages 50-69 years. PREVENTION RELEVANCE: We show that a risk-based approach to mammography screening for German women can help detect breast cancer in women ages 40-49 years with increased risk and reduce screening costs and burdens for low-risk women ages 50-69 years. However, before recommending a particular implementation of a risk-based mammographic screening approach, further investigations of models and thresholds used are needed.

Project description:BackgroundNumerous studies over the past four decades have revealed that breast cancer screening (BCS) significantly reduces breast cancer (BC) mortality. However, in BRICS-plus countries, the association between BCS and BC case fatality and disability are unknown. This study examines the association of different BCS approaches with age-standardized mortality, case-fatality, and disability-adjusted life years (DALYs) rates, as well as with other biological and sociodemographic risk variables, across BRICS-plus from a national and economic perspective.MethodsIn this ecological study applying mixed-effect multilevel regression models, a country-specific dataset was analyzed by combining data from the Global Burden of Disease study 2019 on female age-standardized BC mortality, incidence, and DALYs rates with information on national/regional BCS availability (against no such program or only a pilot program) and BCS type (only self-breast examination (SBE) and/or clinical breast examination (CBE) [SBE/CBE] versus SBE/CBE with mammographic screening availability [MM and/or SBE/CBE] versus SBE/CBE/mammographic with digital mammography and/or ultrasound (US) [DMM/US and/or previous tests] in BRICS-plus countries.ResultsCompared to self/clinical breast examinations (SBE/CBE) across BRICS-plus, more complex BCS program availability was the most significant predictor of decreased mortality [MM and/or SBE/CBE: - 2.64, p < 0.001; DMM/US and/or previous tests: - 1.40, p < 0.001]. In the BRICS-plus, CVD presence, high BMI, second-hand smoke, and active smoking all contributed to an increase in BC mortality and DALY rate. High-income and middle-income regions in BRICS-plus had significantly lower age-standardized BC mortality, case-fatality, and DALYs rates than low-income regions when nationwide BC screening programs were implemented.ConclusionsThe availability of mammography (digital or traditional) and BCS is associated with breast cancer burden in BRICS-plus countries, with regional variations. In light of high-quality evidence from previous causal studies, these findings further support the preventive role of mammography screening for BCS at the national level. Intervening on BCS related risk factors may further reduce the disease burden associated with BC.

Project description:BackgroundExcess body weight and sub-optimal lifestyle are modifiable causes of breast cancer and other diseases. There is little evidence that behaviour change is possible within screening programmes and whether this is influenced by prior knowledge of disease risk. We determined whether breast cancer risk influences uptake, retention and efficacy of a weight control programme in the UK National Health Service Breast Screening Programme, and whether additional cardiovascular disease and type 2 diabetes risk information improves uptake and retention further.MethodOverweight/obese women in the UK National Health Service Breast Screening Programme identified at high, moderately increased, average and low-risk of breast cancer were randomised to receive individualised breast cancer risk information (breast cancer prevention programme), or individualised breast cancer, cardiovascular disease (QRISK2) and type 2 diabetes (QDiabetes, HbA1c) information (multiple disease prevention programme). Personalised breast cancer risk feedback was given before randomisation in Study-1, and after randomisation in Study-2.ResultsRecruitment was 9% (126/1356) in Study-1 and 7% (52/738) in Study-2. With respect to breast cancer risk, odds ratio of uptake for high/moderately increased vs low risk women was 1.99 (95% CI 1.24-3.17, P = 0.004) in Study-1 and 3.58 (95% CI 1.59-8.07, P = 0.002) in Study-2. Odds ratio of retention for high/moderately increased -risk vs. low risk women was 2.98 (95% CI 1.05-8.47, P = 0.041) in Study-1 and 3.88 (95% CI 1.07-14.04, P = 0.039) in Study-2. Weight loss of ≥5% at 12 months was achieved by 63% high/moderate vs. 43% low-risk women in Study-1 (P = 0.083) and 39% vs. 8% in Study-2 (P = 0.008). Uptake, retention and weight loss were equivalent in both the breast cancer prevention programme and the multiple disease prevention programme in both studies.ConclusionsWomen who are informed that they are at increased breast cancer risk were significantly more likely to join and remain in the programmes and consequently lose more weight across both studies. High risk women are more likely engage in a lifetyle prevention programme and also have the greatest potential benefit fom risk reduction strategies.Trial registrationISRCTN91372184 Registered 28 September 2014.

Dataset Information

Estimating the frequency of indolent breast cancer in screening trials.

Publications

Estimating the frequency of indolent breast cancer in screening trials.

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