Background Despite trials of mammography and widespread use, optimal screening policy is controversial. Design and Objective Six models use common data elements to evaluate US screening strategies. Data Sources The models use national data on age-specific incidence, competing mortality, mammography characteristics and treatment effects. Target Population and Time Horizon A contemporary population cohort followed over their lifetimes. Perspective We use a societal perspective for analysis. Interventions We evaluate 20 screening strategies with varying initiation and cessation ages applied annually or biennially. Outcome Measures Number of mammograms, breast cancer mortality reduction or life years gained [LYG] (vs. no screening), false positives, unnecessary biopsies and over-diagnosis. Results of Base Case The 6 models produce consistent rankings of screening strategies. Screening biennially maintains an average of 81% (range across strategies and models 67–99%) of the benefit of annual screening with almost half the number of false positives. Screening biennially from ages 50 to 69 achieves a median 16.5% (range 15%–23%) breast cancer mortality reduction vs. no screening. Initiating biennial screening at age 40 (vs. 50) reduces mortality by an additional 3% (range 1%–6%), consumes more resources and yields more false positives. Biennial screening after age 69 yields some additional mortality reduction in all models but over-diagnosis increases most substantially at older ages. Sensitivity Analysis Results Varying test sensitivity or treatment patterns do not change conclusions. Limitations Results do not include morbidity from false positives, knowledge of earlier diagnosis or under-going unnecessary treatment. Conclusion Biennial screening achieves most of the benefit of annual screening with less harm. Decisions about the best strategy depend on program and individual objectives and the weight placed on benefits, harms and resource considerations.

Breast MRI screening is more cost-effective for BRCA1 than BRCA2 mutation carriers. The cost-effectiveness of adding MRI to mammography varies greatly by age.

Key Points This study is a retrospective analysis of long-term outcomes of patients with FL treated at Stanford University for 4 decades. Study results showed significant improvement in OS in patients with FL despite no change in event-free survival after first-line therapy.

A B S T R A C T PurposeWomen with BRCA1/2 mutations inherit high risks of breast and ovarian cancer; options to reduce cancer mortality include prophylactic surgery or breast screening, but their efficacy has never been empirically compared. We used decision analysis to simulate risk-reducing strategies in BRCA1/2 mutation carriers and to compare resulting survival probability and causes of death. MethodsWe developed a Monte Carlo model of breast screening with annual mammography plus magnetic resonance imaging (MRI) from ages 25 to 69 years, prophylactic mastectomy (PM) at various ages, and/or prophylactic oophorectomy (PO) at ages 40 or 50 years in 25-year-old BRCA1/2 mutation carriers. ResultsWith no intervention, survival probability by age 70 is 53% for BRCA1 and 71% for BRCA2 mutation carriers. The most effective single intervention for BRCA1 mutation carriers is PO at age 40, yielding a 15% absolute survival gain; for BRCA2 mutation carriers, the most effective single intervention is PM, yielding a 7% survival gain if performed at age 40 years. The combination of PM and PO at age 40 improves survival more than any single intervention, yielding 24% survival gain for BRCA1 and 11% for BRCA2 mutation carriers. PM at age 25 instead of age 40 offers minimal incremental benefit (1% to 2%); substituting screening for PM yields a similarly minimal decrement in survival (2% to 3%). ConclusionAlthough PM at age 25 plus PO at age 40 years maximizes survival probability, substituting mammography plus MRI screening for PM seems to offer comparable survival. These results may guide women with BRCA1/2 mutations in their choices between prophylactic surgery and breast screening.

Invasive breast cancer is commonly staged as local, regional or distant disease. We present a stochastic model of the natural history of invasive breast cancer that quantifies (1) the relative rate that the disease transitions from the local, regional to distant stages, (2) the tumour volume at the stage transitions and (3) the impact of symptom-prompted detection on the tumour size and stage of invasive breast cancer in a population not screened by mammography. By symptom-prompted detection, we refer to tumour detection that results when symptoms appear that prompt the patient to seek clinical care. The model assumes exponential tumour growth and volume-dependent hazard functions for the times to symptomatic detection and stage transitions. Maximum likelihood parameter estimates are obtained based on SEER data on the tumour size and stage of invasive breast cancer from patients who were symptomatically detected in the absence of screening mammography. Our results indicate that the rate of symptom-prompted detection is similar to the rate of transition from the local to regional stage and an order of magnitude larger than the rate of transition from the regional to distant stage. We demonstrate that, in the even absence of screening mammography, symptom-prompted detection has a large effect on reducing the occurrence of distant staged disease at initial diagnosis.