Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, BC, Canada.
Department of Medical Oncology, BC Cancer Agency, Vancouver, BC, Canada.
Gynecol Oncol. 2019 Mar;152(3):459-464. doi: 10.1016/j.ygyno.2018.10.014.
Women with high-grade serous ovarian cancer (HGSC) have a 20% chance of carrying a BRCA1 or 2 mutation. Not all undergo genetic testing, and there is a large legacy group of untested patients. Their female first-degree relatives (FDR) may not qualify for testing unless they have specific ethnicity, or personal/family cancer history. We conducted a cost-effectiveness analysis to evaluate risk-reducing strategies for these FDR who are ineligible for testing.
A Markov Monte Carlo simulation model estimated the costs and benefits of 3 strategies for female FDR of HGSC patients whose BRCA status is unknown: (1) no BRCA testing; (2) universal BRCA testing, followed by risk-reducing bilateral salpingo-oophorectomy (RRBSO) for mutation carriers; (3) universal RRBSO, without BRCA testing. Effectiveness was estimated in quality-adjusted life year (QALY) gains over a 50-year time horizon. Sensitivity analyses accounted for uncertainty around various parameters.
Universal BRCA testing for female FDR of women with HGSC yielded a higher average QALY gain at acceptable cost compared to no BRCA testing, with an incremental cost-effectiveness ratio of $7888 per QALY. Universal BRCA testing was more effective and less costly than universal RRBSO (19.20 QALYs vs. 18.52 QALYs, and $10,135 vs. $14,231, respectively). Results were stable over wide ranges of plausible costs and estimates. Compliance with hormone replacement therapy had to exceed 79.3% for universal RRBSO to be the most effective strategy.
BRCA mutation testing should be offered to all female first-degree relatives of women with high-grade serous ovarian cancer when BRCA mutation status is unknown.
患有高级别浆液性卵巢癌（HGSC）的女性有 20%的机会携带 BRCA1 或 2 基因突变。并非所有患者都接受基因检测，还有大量未经检测的患者。她们的女性一级亲属（FDR）除非具有特定的种族或个人/家族癌症史，否则可能不符合检测条件。我们进行了一项成本效益分析，以评估这些不符合检测条件的 FDR 的风险降低策略。
采用马尔可夫蒙特卡罗模拟模型，估算了 3 种针对 BRCA 状态未知的 HGSC 患者的女性 FDR 的风险降低策略的成本效益：（1）不进行 BRCA 检测；（2）对所有女性 FDR 进行 BRCA 检测，然后对突变携带者进行双侧输卵管卵巢切除术（RRBSO）；（3）对所有女性 FDR 进行 RRBSO，不进行 BRCA 检测。在 50 年的时间内，通过增加质量调整生命年（QALY）来评估有效性。敏感性分析考虑了各种参数的不确定性。
与不进行 BRCA 检测相比，对 HGSC 女性的女性 FDR 进行普遍 BRCA 检测可获得更高的平均 QALY 收益，增量成本效益比为每 QALY7888 美元。与普遍 RRBSO 相比，普遍 BRCA 检测更有效且成本更低（分别为 19.20 QALYs 和 18.52 QALYs，以及 10135 美元和 14231 美元）。在广泛的合理成本和估计范围内，结果都是稳定的。要使普遍 RRBSO 成为最有效的策略，激素替代疗法的依从率必须超过 79.3%。
当 BRCA 突变状态未知时，应向所有患有高级别浆液性卵巢癌的女性的女性一级亲属提供 BRCA 突变检测。
