Precision prophylaxis: Identifying the optimal timing for risk-reducing salpingo-oophorectomy based on type of BRCA1 and BRCA2 cluster region mutations.
Precision prophylaxis: Identifying the optimal timing for risk-reducing salpingo-oophorectomy based on type of BRCA1 and BRCA2 cluster region mutations.
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DOI：
10.1016/j.ygyno.2019.11.036
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发表时间：
2020-02
影响因子：
4.7
通讯作者：
Rebbeck, Timothy R.
中科院分区：
文献类型：
--
作者：
Solsky, Ian;Chen, Jinbo;Rebbeck, Timothy R.
目前针对BRCA1/2突变个体的降低风险输卵管卵巢切除术(RRSO)指南没有考虑到BRCA1/2簇区突变与乳腺癌和卵巢癌发生的不同风险相关的风险可变性。我们评估了目前的建议是否适用于考虑突变特定风险的个体患者。利用BRCA1/2突变患者的假设队列，我们建立了马尔可夫模型，允许根据BRCA1/2突变、聚集区突变(卵巢癌聚集区(OCCR)、乳腺癌聚集区(BCCR)或非BCCR/OCCR)的存在、BRCA1/2诊断时的年龄(20-65)和RSO时的年龄(21-80)来估计平均预期寿命。对于所有BRCA1/2突变类型，最好的策略是尽早接受RRSO。对于延迟RRSO的BRCA1/2携带者或在晚年被确认为突变的人，OCCR突变往往与比BCCR和非BCCR/OCCR突变相关的预期寿命更低。RRSO的最小延迟(即相邻的5年间隔)与预期寿命的轻微损失有关。对预期寿命影响最大的变量包括RRSO后的卵巢癌风险、乳腺癌死亡率、与RRSO相关的非癌症死亡率以及乳腺癌的分期分布。BRCA1/2多国区域可以在咨询和共同决策方面提供更准确的预期寿命估计。RRSO最合适的时机是一个复杂的决定，必须为每个患者个体化。
Current risk-reducing salpingo-oophorectomy (RRSO) guidelines for individuals with BRCA1/2 mutations do not account for risk variability due to BRCA1/2 cluster region mutations that are associated with varying risks for the development of breast and ovarian cancer. We assessed whether current recommendations are appropriate for individual patients considering mutation-specific risks. Using a hypothetical cohort of patients with BRCA1/2 mutations, we constructed Markov models allowing for the estimation of mean life expectancy based upon BRCA1/2 mutation, the presence of a cluster region mutation (Ovarian Cancer Cluster Region (OCCR), Breast Cancer Cluster Region (BCCR), or non-BCCR/OCCR), age at time of BRCA1/2 diagnosis (20–65), and age at time of RRSO (21–80). For all BRCA1/2 mutation types, the optimal strategy was to undergo RRSO as early as possible. For BRCA1/2 carriers who delayed RRSO or who were identified with a mutation later in life, the OCCR mutation tended to be associated with lower life expectancy estimates than the BCCR and non-BCCR/OCCR mutations. Minimal delays in RRSO (i.e., neighboring 5-year intervals) were associated with minor losses in life expectancy. Variables associated with greatest impact on life expectancy included ovarian cancer risk after RRSO, breast cancer mortality rate, non-cancer mortality associated with RRSO, and breast cancer stage distribution. BRCA1/2 cluster regions may provide more precise estimates of life expectancy in counselling and shared decision-making. The most appropriate timing for RRSO is a complex decision and must be individualized for each patient.
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