Molecular imaging with positron emission tomography and computed tomography (PET/CT) for selecting first-line targeted treatment in metastatic breast cancer: a cost-effectiveness study.

Our aim was to evaluate the potential cost-effectiveness of PET/CT with FES and 89Zr-trastuzumab compared to pathology to select first-line targeted treatment in metastatic breast cancer (MBC) patients with non-rapidly progressive disease. A previously published and validated model was extended and adapted for this analysis. Two alternative scenarios were compared. In the care as usual pathway first-line targeted treatment of MBC patients was assigned on the basis of pathology results, while in the intervention pathway treatment selection was based on the results from the PET/CT imaging. Costs, life years gained (LYG) and incremental cost-effectiveness ratios (ICER) were calculated. More MBC lesions were detected in the intervention pathway than in the care as usual pathway. The diagnostic costs to evaluate the receptor status and the treatment costs were higher in the intervention strategy, as were total costs and total LYG. The ICER for replacing biopsies with PET/CT imaging with FES and 89Zr-trastuzumab, assuming sensitivity of 77.1% and specificity of 80%, ranged from €71,000 to €77,000 per LYG. When assuming sensitivity of 80% and specificity of 76.7%, the ICER for replacing biopsies with PET/CT imaging with FES and 89Zr-trastuzumab ranged from to €74,000 to €80,000 per LYG. The application of PET/CT with FES and 89Zr-trastuzumab in first-line treatment selection for MBC patients has the potential to be a cost-effective intervention. Our analysis demonstrated that even a small increase in the sensitivity and the specificity of PET/CT can have a large impact on its potential cost-effectiveness.

A modelling study to evaluate the costs and effects of lowering the starting age of population breast cancer screening.

BACKGROUND: Because the incidence of breast cancer increases between 45 and 50years of age, a reconsideration is required of the current starting age (typically 50years) for routine mammography. Our aim was to evaluate the quantitative benefits, harms, and cost-effectiveness of lowering the starting age of breast cancer screening in the Dutch general population. METHODS: Economic modelling with a lifelong perspective compared biennial screening for women aged 48-74years and for women aged 46-74years with the current Dutch screening programme, which screen women between the ages of 50 and 74years. Tumour deaths prevented, years of life saved (YOLS), false-positive rates, radiation-induced tumours, costs and incremental cost-effectiveness ratios (ICERs) were evaluated. RESULTS: Starting the screening at 48 instead of 50 years of age led to increases in: the number of small tumours detected (4.0%), tumour deaths prevented (5.6%), false positives (9.2%), YOLS (5.6%), radiation-induced tumours (14.7%), and costs (4.1%). Starting the screening at 46 instead of 48 years of age increased the number of small tumours detected (3.3%), tumour deaths prevented (4.2%), false positives (8.8%), YOLS (3.7%), radiation-induced tumours (15.2%), and costs (4.0%). The ICER was €5600/YOLS for the 48-74 scenario and €5600/YOLS for the 46-74 scenario. CONCLUSIONS: Women could benefit from lowering the starting age of screening as more breast cancer deaths would be averted. Starting regular breast cancer screening earlier is also cost-effective. As the number of additional expected harms is relatively small in both the scenarios examined, and the difference in ICERs is not large, introducing two additional screening rounds is justifiable.

Increased life expectancy as a result of non-hormonal targeted therapies for HER2 or hormone receptor positive metastatic breast cancer: A systematic review and meta-analysis.

This article aimed to assess the clinical effectiveness of non-hormonal targeted therapies (TTs) in terms of increase of median progression-free survival (PFS) and overall survival (OS) in receptor-positive metastatic breast cancer (MBC) patients by performing a systematic review and meta-analysis. We systematically searched relevant randomized controlled trials and extracted data about number of patients on targeted and comparator therapy, receptor status, line of treatment, median PFS and OS, p values, hazard ratios (HRs) and 95% confidence intervals (CI). Inverse variance was used to estimate pooled HRs, chi-square test for heterogeneity and Jadad scale for quality were applied. Thirty-eight studies (n=17,192 patients) were eligible for inclusion. TTs added 3.3months to the median PFS [0.7-9.6; HRs 0.74, 95% CI 0.71-0.77] of receptor-positive MBC patients and prolonged their median OS with 3.5months [0-4.7; HRs 0.90, 95% CI 0.82-0.98]. The highest increase in median PFS of 3.6months was found in HER2-/hormone receptor(HR)+ patients, while the highest increase in median OS of 7.2months was observed in HER2+/HRmixed status patients. First-line TTs were most effective in increasing the median PFS in the HR+/HER2- group with 2.0months, and in the HER2+/HRmixed group by adding 4.7months to the median OS. Second-line TTs were most effective for HER2-/HR+ patients by adding 2.6months to their PFS, and for HER2+/HRmixed patients by adding 3.1months to their median OS. Albeit small, the gain in months of median PFS and median OS was significant. Importantly, the results reported show large variation, and thus routinely applying a personalized approach seems warranted.

Simulation models in population breast cancer screening: A systematic review.

The aim of this review was to critically evaluate published simulation models for breast cancer screening of the general population and provide a direction for future modeling. A systematic literature search was performed to identify simulation models with more than one application. A framework for qualitative assessment which incorporated model type; input parameters; modeling approach, transparency of input data sources/assumptions, sensitivity analyses and risk of bias; validation, and outcomes was developed. Predicted mortality reduction (MR) and cost-effectiveness (CE) were compared to estimates from meta-analyses of randomized control trials (RCTs) and acceptability thresholds. Seven original simulation models were distinguished, all sharing common input parameters. The modeling approach was based on tumor progression (except one model) with internal and cross validation of the resulting models, but without any external validation. Differences in lead times for invasive or non-invasive tumors, and the option for cancers not to progress were not explicitly modeled. The models tended to overestimate the MR (11-24%) due to screening as compared to optimal RCTs 10% (95% CI - 2-21%) MR. Only recently, potential harms due to regular breast cancer screening were reported. Most scenarios resulted in acceptable cost-effectiveness estimates given current thresholds. The selected models have been repeatedly applied in various settings to inform decision making and the critical analysis revealed high risk of bias in their outcomes. Given the importance of the models, there is a need for externally validated models which use systematical evidence for input data to allow for more critical evaluation of breast cancer screening.