Cost-effectiveness of MRI compared to mammography for breast cancer screening in a high risk population

<p>Abstract</p> <p>Background</p> <p>Breast magnetic resonance imaging (MRI) is a sensitive method of breast imaging virtually uninfluenced by breast density. Because of the improved sensitivity, breast MRI is increasingly being used for detection of breast cancer among high risk young women. However, the specificity of breast MRI is variable and costs are high. The purpose of this study was to determine if breast MRI is a cost-effective approach for the detection of breast cancer among young women at high risk.</p> <p>Methods</p> <p>A Markov model was created to compare annual breast cancer screening over 25 years with either breast MRI or mammography among young women at high risk. Data from published studies provided probabilities for the model including sensitivity and specificity of each screening strategy. Costs were based on Medicare reimbursement rates for hospital and physician services while medication costs were obtained from the Federal Supply Scale. Utilities from the literature were applied to each health outcome in the model including a disutility for the temporary health state following breast biopsy for a false positive test result. All costs and benefits were discounted at 5% per year. The analysis was performed from the payer perspective with results reported in 2006 U.S. dollars. Univariate and probabilistic sensitivity analyses addressed uncertainty in all model parameters.</p> <p>Results</p> <p>Breast MRI provided 14.1 discounted quality-adjusted life-years (QALYs) at a discounted cost of $18,167 while mammography provided 14.0 QALYs at a cost of$4,760 over 25 years of screening. The incremental cost-effectiveness ratio of breast MRI compared to mammography was $179,599/QALY. In univariate analysis, breast MRI screening became <$50,000/QALY when the cost of the MRI was < $315. In the probabilistic sensitivity analysis, MRI screening produced a net health benefit of -0.202 QALYs (95$50,000/QALY. Breast MRI screening was superior in 0%, < $50,000/QALY in 22$50,000/QALY in 34%, and inferior in 44% of trials.</p> <p>Conclusion</p> <p>Although breast MRI may provide health benefits when compared to mammographic screening for some high risk women, it does not appear to be cost-effective even at willingness to pay thresholds above $120,000/QALY.</p

Mutational signatures in esophageal adenocarcinoma define etiologically distinct subgroups with therapeutic relevance.

Esophageal adenocarcinoma (EAC) has a poor outcome, and targeted therapy trials have thus far been disappointing owing to a lack of robust stratification methods. Whole-genome sequencing (WGS) analysis of 129 cases demonstrated that this is a heterogeneous cancer dominated by copy number alterations with frequent large-scale rearrangements. Co-amplification of receptor tyrosine kinases (RTKs) and/or downstream mitogenic activation is almost ubiquitous; thus tailored combination RTK inhibitor (RTKi) therapy might be required, as we demonstrate in vitro. However, mutational signatures showed three distinct molecular subtypes with potential therapeutic relevance, which we verified in an independent cohort (n = 87): (i) enrichment for BRCA signature with prevalent defects in the homologous recombination pathway; (ii) dominant T>G mutational pattern associated with a high mutational load and neoantigen burden; and (iii) C>A/T mutational pattern with evidence of an aging imprint. These subtypes could be ascertained using a clinically applicable sequencing strategy (low coverage) as a basis for therapy selection.Whole-genome sequencing of esophageal adenocarcinoma samples was performed as part of the International Cancer Genome Consortium (ICGC) through the oEsophageal Cancer Clinical and Molecular Stratification (OCCAMS) Consortium and was funded by Cancer Research UK. We thank the ICGC members for their input on verification standards as part of the benchmarking exercise. We thank the Human Research Tissue Bank, which is supported by the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre, from Addenbrooke’s Hospital and UCL. Also the University Hospital of Southampton Trust and the Southampton, Birmingham, Edinburgh and UCL Experimental Cancer Medicine Centres and the QEHB charities. This study was partly funded by a project grant from Cancer Research UK. R.C.F. is funded by an NIHR Professorship and receives core funding from the Medical Research Council and infrastructure support from the Biomedical Research Centre and the Experimental Cancer Medicine Centre. We acknowledge the support of The University of Cambridge, Cancer Research UK (C14303/A17197) and Hutchison Whampoa Limited. We would like to thank Dr. Peter Van Loo for providing the NGS version of ASCAT for copy number calling. We are grateful to all the patients who provided written consent for participation in this study and the staff at all participating centres. Some of the work was undertaken at UCLH/UCL who received a proportion of funding from the Department of Health’s NIHR Biomedical Research Centres funding scheme. The work at UCLH/UCL was also supported by the CRUK UCL Early Cancer Medicine Centre.This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/ng.365

Emerging concepts in biomarker discovery; The US-Japan workshop on immunological molecular markers in oncology

Supported by the Office of International Affairs, National Cancer Institute (NCI), the "US-Japan Workshop on Immunological Biomarkers in Oncology" was held in March 2009. The workshop was related to a task force launched by the International Society for the Biological Therapy of Cancer (iSBTc) and the United States Food and Drug Administration (FDA) to identify strategies for biomarker discovery and validation in the field of biotherapy. The effort will culminate on October 28th 2009 in the "iSBTc-FDA-NCI Workshop on Prognostic and Predictive Immunologic Biomarkers in Cancer", which will be held in Washington DC in association with the Annual Meeting. The purposes of the US-Japan workshop were a) to discuss novel approaches to enhance the discovery of predictive and/or prognostic markers in cancer immunotherapy; b) to define the state of the science in biomarker discovery and validation. The participation of Japanese and US scientists provided the opportunity to identify shared or discordant themes across the distinct immune genetic background and the diverse prevalence of disease between the two Nations