The Early Detection of Breast Cancer Using Liquid Biopsies: Model Estimates of the Benefits, Harms, and Costs.
The Early Detection of Breast Cancer Using Liquid Biopsies: Model Estimates of the Benefits, Harms, and Costs.
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乳腺癌筛查与益处有关，如降低死亡率和改善生活质量，也与危害有关，如假阳性结果，过度诊断和成本。可以考虑采用新的筛查方法来减少筛查的危害，增加筛查的益处。液体活检已被提出作为一种新的方法，用于早期发现乳腺癌。然而，研究表明，基于无细胞DNA的液体活检对早期乳腺癌的敏感性较低。使用微观模拟模型MISCAN-Fadia，我们模拟了不同水平的液体活检敏感性和特异性的液体活检早期检测乳腺癌的益处，危害和成本。我们发现，鉴于基于CCGA子研究的测试性能，液体活检不太可能成为数字乳腺X射线摄影的替代品。当液体活检无法检测乳腺癌的前体病变-导管原位癌（DCIS）时，它们需要能够以低成本检测小的早期肿瘤，具有高特异性，以便成为数字乳腺X射线摄影的替代品。我们估计液体活检的最高价格为187美元，大大低于目前的上市价格。乳腺癌筛查与危害有关，例如假阳性和过度诊断，因此可以考虑新的筛查测试。液体活检已被提出作为一种新的方法用于早期检测癌症，但低细胞游离DNA肿瘤分数可能会造成一个问题，用于人口筛选。使用乳腺癌微观模拟模型MISCAN-Fadia，我们估计了在美国50至74岁的女性中使用液体活检进行乳腺癌筛查的结果。对于检测灵敏度和特异性的不同组合，我们量化了使用液体活检对筛查的危害和益处的影响，并且我们估计了在乳腺癌筛查中成本效益实施的最高液体活检价格为50，000美元的成本效益阈值。我们调查了在什么条件下液体活检可能是数字乳腺X线摄影的合适替代方案，并将这些条件与CCGA子研究进行了比较。结果与数字乳腺X线摄影筛查进行了比较，包括死亡率降低，过度诊断，质量调整生命年（Qs），以及液体活检的最高价格，以实现成本效益。当液体活检无法检测DCIS时，可以防止很大一部分过度诊断病例，但与数字乳房X线摄影筛查相比，整体乳腺癌死亡率降低和生活质量降低，成本更高。液体活检的价格应限制在每液体活检187美元，这取决于测试性能。总的来说，无法检测导管原位癌（DCIS）的液体活检需要能够以低成本检测小的早期肿瘤，具有高特异性，以便成为数字乳腺X线摄影的替代品。液体活检可能更适合作为数字乳腺X线摄影的补充，而不是替代品。
Breast cancer screening is associated with benefits, such as mortality reduction and improved quality of life, and harms, such as false-positive results, overdiagnoses, and costs. Novel screen tests could be considered to reduce the harms and increase the benefits of screening. Liquid biopsies have been proposed as a novel method for the early detection of breast cancer. However, studies show that liquid biopsies based on cell-free DNA have a low sensitivity for early-stage breast cancer. Using the microsimulation model MISCAN-Fadia, we model the benefits, harms, and costs of the early detection of breast cancer using liquid biopsies for varying levels of liquid biopsy sensitivity and specificity. We found that liquid biopsies are unlikely to be an alternative to digital mammography, given the test performance based on a CCGA substudy. When liquid biopsies are unable to detect the precursor lesion of breast cancer—ductal carcinoma in situ (DCIS)—they need to be able to detect small, early-stage tumors, with high specificity, at low costs in order to be an alternative to digital mammography. We estimated a maximum liquid biopsy price of USD 187, which is substantially lower than currently listed prices. Breast cancer screening is associated with harms, such as false-positives and overdiagnoses, and, thus, novel screen tests can be considered. Liquid biopsies have been proposed as a novel method for the early detection of cancer, but low cell-free DNA tumor fraction might pose a problem for the use in population screening. Using breast cancer microsimulation model MISCAN-Fadia, we estimated the outcomes of using liquid biopsies in breast cancer screening in women aged 50 to 74 in the United States. For varying combinations of test sensitivity and specificity, we quantify the impact of the use of liquid biopsies on the harms and benefits of screening, and we estimate the maximum liquid biopsy price for cost-effective implementation in breast cancer screening at a cost-effectiveness threshold of USD 50,000. We investigate under what conditions liquid biopsies could be a suitable alternative to digital mammography and compare these conditions to a CCGA substudy. Outcomes were compared to digital mammography screening, and include mortality reduction, overdiagnoses, quality-adjusted life-years (QALYs), and the maximum price of a liquid biopsy for cost-effective implementation. When liquid biopsies are unable to detect DCIS, a large proportion of overdiagnosed cases is prevented but overall breast cancer mortality reduction and quality of life are lower, and costs are higher compared to digital mammography screening. Liquid biopsies prices should be restricted to USD 187 per liquid biopsy depending on test performance. Overall, liquid biopsies that are unable to detect ductal carcinoma in situ (DCIS) need to be able to detect small, early-stage tumors, with high specificity, at low costs in order to be an alternative to digital mammography. Liquid biopsies might be more suitable as an addition to digital mammography than as an alternative.
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DOI：
10.1016/j.annonc.2020.02.011
发表时间：
2020-06
期刊：
Annals of oncology : official journal of the European Society for Medical Oncology
影响因子：
--
作者：
Liu MC;Oxnard GR;Klein EA;Swanton C;Seiden MV;CCGA Consortium
通讯作者：
CCGA Consortium
影响因子：
3.8
作者：
Hubbell, Earl;Clarke, Christina A.;Berg, Christine D.
通讯作者：
Berg, Christine D.
影响因子：
19.7
作者：
Lehman, Constance D.;Arao, Robert F.;Miglioretti, Diana L.
通讯作者：
Miglioretti, Diana L.
通过碎片尺寸分析增强了循环肿瘤DNA的检测。
影响因子：
17.1
作者：
Mouliere F;Chandrananda D;Piskorz AM;Moore EK;Morris J;Ahlborn LB;Mair R;Goranova T;Marass F;Heider K;Wan JCM;Supernat A;Hudecova I;Gounaris I;Ros S;Jimenez-Linan M;Garcia-Corbacho J;Patel K;Østrup O;Murphy S;Eldridge MD;Gale D;Stewart GD;Burge J;Cooper WN;van der Heijden MS;Massie CE;Watts C;Corrie P;Pacey S;Brindle KM;Baird RD;Mau-Sørensen M;Parkinson CA;Smith CG;Brenton JD;Rosenfeld N
通讯作者：
Rosenfeld N
DOI：
10.1177/0272989x17700624
发表时间：
2018-04
期刊：
Medical decision making : an international journal of the Society for Medical Decision Making
影响因子：
--
作者：
Mandelblatt JS;Near AM;Miglioretti DL;Munoz D;Sprague BL;Trentham-Dietz A;Gangnon R;Kurian AW;Weedon-Fekjaer H;Cronin KA;Plevritis SK
通讯作者：
Plevritis SK