Context: Women with inherited BRCA1/2 mutations are at high risk for breast cancer, which mammography often misses. Screening with contrast-enhanced breast magnetic resonance imaging (MRI) detects cancer earlier but increases costs and results in more false-positive scans.
Objective: To evaluate the cost-effectiveness of screening BRCA1/2 mutation carriers with mammography plus breast MRI compared with mammography alone.
Design, Setting, And Patients: A computer model that simulates the life histories of individual BRCA1/2 mutation carriers, incorporating the effects of mammographic and MRI screening was used. The accuracy of mammography and breast MRI was estimated from published data in high-risk women. Breast cancer survival in the absence of screening was based on the Surveillance, Epidemiology and End Results database of breast cancer patients diagnosed in the prescreening period (1975-1981), adjusted for the current use of adjuvant therapy. Utilization rates and costs of diagnostic and treatment interventions were based on a combination of published literature and Medicare payments for 2005.
Main Outcome Measures: The survival benefit, incremental costs, and cost-effectiveness of MRI screening strategies, which varied by ages of starting and stopping MRI screening, were computed separately for BRCA1 and BRCA2 mutation carriers.
Results: Screening strategies that incorporate annual MRI as well as annual mammography have a cost per quality-adjusted life-year (QALY) gained ranging from less than 45,000 dollars to more than 700,000 dollars, depending on the ages selected for MRI screening and the specific BRCA mutation. Relative to screening with mammography alone, the cost per QALY gained by adding MRI from ages 35 to 54 years is 55,420 dollars for BRCA1 mutation carriers, 130,695 dollars for BRCA2 mutation carriers, and 98,454 dollars for BRCA2 mutation carriers who have mammographically dense breasts.
Conclusions: 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.
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http://dx.doi.org/10.1001/jama.295.20.2374 | DOI Listing |
Curr Protoc
January 2025
Myriad Genetic Laboratories, Inc., Salt Lake City, Utah.
Balanced translocation carriers experience elevated reproductive risks, including pregnancy loss and children with anomalies due to generating chromosomally unbalanced gametes. While understanding the likelihood of producing unbalanced conceptuses is critical for individuals to make reproductive decisions, risk estimates are difficult to obtain as most balanced translocations are unique. To improve reproductive risk estimates, Drs.
View Article and Find Full Text PDFUnlabelled: Autism Spectrum Disorder (ASD) is characterized by restricted and repetitive behaviors and social differences, both of which may manifest, in part, from underlying differences in corticostriatal circuits and reinforcement learning. Here, we investigated reinforcement learning in mice with mutations in either or , both high-confidence ASD risk genes associated with major syndromic forms of ASD. Using an odor-based two-alternative forced choice (2AFC) task, we tested adolescent mice of both sexes and found male and heterozygote (Het) mice showed enhanced learning performance compared to their wild type (WT) siblings.
View Article and Find Full Text PDFJ Alzheimers Dis
January 2025
Department of Neurology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Background: Understanding the sequential progression of cognitive decline in autosomal dominant Alzheimer's disease (ADAD) in the Latino population is crucial for enhancing early identification for targeted interventions. Given the tablet-based administration and increasing frequency of use in epidemiological research, validating this progression within the NIH Toolbox cognitive battery (NIHTB-CB) is important.
Objective: The first aim was to utilize an innovative Event-Based Modeling (EBM) analytic approach to estimate the sequence of cognitive declines in persons at risk for ADAD enriched for being of Latino origin.
FEBS Lett
January 2025
Department of Chemistry, Tokyo Institute of Technology (Institute of Science Tokyo), Japan.
Modular polyketide synthases (PKSs) are multi-domain enzymes involved in the biosynthesis of polyketide natural products. The dehydratase (DH) domain catalyzes the dehydration of the β-hydroxyacyl unit attached to the acyl carrier protein (ACP) domain in modular PKS. Although the DH domain likely recognizes the cognate ACP domain during the dehydration reaction, the molecular basis of DH-ACP interactions remains elusive.
View Article and Find Full Text PDFStat Med
February 2025
Department of Mathematical Sciences, University of Texas at Dallas, Richardson, Texas, USA.
Multi-gene panel testing allows efficient detection of pathogenic variants in cancer susceptibility genes including moderate-risk genes such as ATM and PALB2. A growing number of studies examine the risk of breast cancer (BC) conferred by pathogenic variants of these genes. A meta-analysis combining the reported risk estimates can provide an overall estimate of age-specific risk of developing BC, that is, penetrance for a gene.
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