Institute for Technology Assessment, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
Cancer. 2013 Mar 15;119(6):1266-76. doi: 10.1002/cncr.27864. Epub 2012 Nov 26.
Current clinical guidelines recommend earlier, more intensive breast cancer screening with both magnetic resonance imaging (MRI) and mammography for women with breast cancer susceptibility gene (BRCA) mutations. Unspecified details of screening schedules are a challenge for implementing guidelines.
A Markov Monte Carlo computer model was used to simulate screening in asymptomatic women who were BRCA1 and BRCA2 mutation carriers. Three dual-modality strategies were compared with digital mammography (DM) alone: 1) DM and MRI alternating at 6-month intervals beginning at age 25 years (Alt25), 2) annual MRI beginning at age 25 years with alternating DM added at age 30 years (MRI25/Alt30), and 3) DM and MRI alternating at 6-month intervals beginning at age 30 years (Alt30). Primary outcomes were quality-adjusted life years (QALYs), lifetime costs (in 2010 US dollars), and incremental cost-effectiveness (dollars per QALY gained). Additional outcomes included potential harms of screening, and lifetime costs stratified into component categories (screening and diagnosis, treatment, mortality, and patient time costs).
All 3 dual-modality screening strategies increased QALYs and costs. Alt30 screening had the lowest incremental costs per additional QALY gained (BRCA1, $74,200 per QALY; BRCA2, $215,700 per QALY). False-positive test results increased substantially with dual-modality screening and occurred more frequently in BRCA2 carriers. Downstream savings in both breast cancer treatment and mortality costs were outweighed by increases in up-front screening and diagnosis costs. The results were influenced most by estimates of breast cancer risk and MRI costs.
Alternating MRI and DM screening at 6-month intervals beginning at age 30 years was identified as a clinically effective approach to applying current guidelines, and was more cost-effective in BRCA1 gene mutation carriers compared with BRCA2 gene mutation carriers.
目前的临床指南建议对携带乳腺癌易感基因(BRCA)突变的女性进行更早、更密集的乳腺癌筛查,包括磁共振成像(MRI)和乳房 X 光检查。由于未明确筛查时间表的具体细节,给指南的实施带来了挑战。
采用 Markov 蒙特卡罗计算机模型模拟无症状的 BRCA1 和 BRCA2 基因突变携带者的筛查情况。将三种双模式策略与单独数字乳房 X 线摄影(DM)进行比较:1)从 25 岁开始,每 6 个月交替进行 DM 和 MRI(Alt25);2)从 25 岁开始每年进行 MRI,30 岁时开始交替进行 DM(MRI25/Alt30);3)从 30 岁开始,每 6 个月交替进行 DM 和 MRI(Alt30)。主要结果是质量调整生命年(QALYs)、终生成本(2010 年美元)和增量成本效益(每获得一个 QALY 的增量成本)。其他结果包括筛查的潜在危害,以及按组成类别(筛查和诊断、治疗、死亡率和患者时间成本)分层的终生成本。
所有三种双模式筛查策略都增加了 QALYs 和成本。Alt30 筛查的增量成本效益比最低(BRCA1 为每 QALY 74200 美元,BRCA2 为每 QALY 215700 美元)。双模式筛查使假阳性检测结果显著增加,BRCA2 携带者的发生率更高。乳腺癌治疗和死亡率成本的降低被前期筛查和诊断成本的增加所抵消。结果受乳腺癌风险和 MRI 成本的估计影响最大。
从 30 岁开始,每 6 个月交替进行 MRI 和 DM 筛查被确定为一种应用当前指南的有效方法,在 BRCA1 基因突变携带者中比 BRCA2 基因突变携带者更具成本效益。