A simulation model to predict the impact of prophylactic surgery and screening on the life expectancy of BRCA1 and BRCA2 mutation carriers.
A simulation model to predict the impact of prophylactic surgery and screening on the life expectancy of BRCA1 and BRCA2 mutation carriers.
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DOI：
10.1158/1055-9965.epi-12-0149
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发表时间：
2012-07
期刊：
影响因子：
--
通讯作者：
Plevritis SK
中科院分区：
文献类型：
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作者：
Sigal BM;Munoz DF;Kurian AW;Plevritis SK
BRCA1或BRCA2 （BRCA1/2）基因遗传突变的女性被推荐接受一系列强化的癌症风险降低策略，包括预防性乳房切除术（PM）、预防性卵巢切除术（PO）和筛查。我们估计了不同年龄的不同风险降低方案对预期寿命的影响。我们应用我们之前开发的蒙特卡罗模拟模型筛选和预防性手术BRCA1/2突变携带者。本文提出了在没有PO的情况下计算年龄特异性乳腺癌发病率的数学公式，作为仿真模型的输入，并对相关模型参数进行敏感性分析。在BRCA1/2突变检测后立即进行PM和PO，预期寿命的最大收益；这些获益随着检测年龄的变化而变化，BRCA1突变携带者的年龄为6.8-10.3岁，BRCA2突变携带者的年龄为3.4-4.4岁。BRCA1基因携带者推迟5-10年预防性手术的预期寿命延长1-9.9年，BRCA2基因突变携带者延长0.5-4.2年。增加年度乳腺筛查，BRCA1的筛查期可延长2.0-9.9年，BRCA2的筛查期可延长1.5-4.3年。结果对我们关于乳腺癌风险降低的幅度和持续时间的假设变化最为敏感。预期寿命的增加取决于BRCA突变的类型和干预时的年龄。敏感性分析表明，由于前列腺癌导致的乳腺癌风险降低程度是预期寿命增加的关键决定因素。进一步研究PO对BRCA1/2突变携带者乳腺癌风险的影响是有必要的。
Women with inherited mutations in the BRCA1 or BRCA2 (BRCA1/2) genes are recommended to undergo a number of intensive cancer risk-reducing strategies, including prophylactic mastectomy (PM), prophylactic oophorectomy (PO) and screening. We estimate the impact of different risk-reducing options at various ages on life expectancy. We apply our previously developed Monte Carlo simulation model of screening and prophylactic surgery in BRCA1/2 mutation carriers. Here we present the mathematical formulation to compute age-specific breast cancer incidence in the absence of PO, which is an input to the simulation model and provide sensitivity analysis on related model parameters. The greatest gains in life expectancy result from performing PM and PO immediately after BRCA1/2 mutation testing; these gains vary with age at testing, from 6.8–10.3 years for BRCA1, and 3.4–4.4 years for BRCA2 mutation carriers. Life expectancy gains from delaying prophylactic surgery by 5–10 years range from 1–9.9 years for BRCA1, and 0.5–4.2 years for BRCA2 mutation carriers. Adding annual breast screening provides gains of 2.0–9.9 years for BRCA1, and 1.5–4.3 years for BRCA2. Results were most sensitive to variations in our assumptions about the magnitude and duration of breast cancer risk reduction due to PO. Life expectancy gains depend on the type of BRCA mutation and age at interventions. Sensitivity analysis identifies the degree of breast cancer risk reduction due to PO as a key determinant of life expectancy gain. Further study of the impact of PO on breast cancer risk in BRCA1/2 mutation carriers is warranted.