Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, NC, USA.
Division of Gynecologic Oncology, Duke University Medical Center, Durham, NC, USA.
Ann Surg Oncol. 2017 Oct;24(11):3116-3123. doi: 10.1245/s10434-017-5995-z. Epub 2017 Jul 11.
The appropriate management of breast cancer risk in BRCA mutation carriers following ovarian cancer diagnosis remains unclear. We sought to determine the survival benefit and cost effectiveness of risk-reducing mastectomy (RRM) among women with BRCA1/2 mutations following stage II-IV ovarian cancer.
We constructed a decision model from a third-party payer perspective to compare annual screening with magnetic resonance imaging (MRI) and mammography to annual screening followed by RRM with reconstruction following ovarian cancer diagnosis. Survival, overall costs, and cost effectiveness were determined by decade at diagnosis using 2015 US dollars. All inputs were obtained from the literature and public databases. Monte Carlo probabilistic sensitivity analysis was performed with a $100,000 willingness-to-pay threshold.
The incremental cost-effectiveness ratio (ICER) per year of life saved (YLS) for RRM increased with age and BRCA2 mutation status, with greater survival benefit demonstrated in younger patients with BRCA1 mutations. RRM delayed 5 years in 40-year-old BRCA1 mutation carriers was associated with 5 months of life gained (ICER $72,739/YLS), and in 60-year-old BRCA2 mutation carriers was associated with 0.8 months of life gained (ICER $334,906/YLS). In all scenarios, $/YLS and mastectomies per breast cancer prevented were lowest with RRM performed 5-10 years after ovarian cancer diagnosis.
For most BRCA1/2 mutation carriers following ovarian cancer diagnosis, RRM performed within 5 years is not cost effective when compared with breast cancer screening. Imaging surveillance should be advocated during the first several years after ovarian cancer diagnosis, after which point the benefits of RRM can be considered based on patient age and BRCA mutation status.
BRCA 基因突变携带者在诊断出卵巢癌后,乳腺癌风险的适当管理仍不清楚。我们旨在确定 BRCA1/2 突变携带者在诊断出 II-IV 期卵巢癌后进行降低风险的乳房切除术(RRM)的生存获益和成本效益。
我们从第三方支付者的角度构建了一个决策模型,以比较在卵巢癌诊断后每年进行磁共振成像(MRI)和乳房 X 线照相术筛查与每年进行筛查后进行 RRM 并在卵巢癌诊断后进行重建的情况。使用 2015 年美元计算了诊断后的每个十年的生存、总成本和成本效益。所有投入均来自文献和公共数据库。使用 10 万美元的意愿支付阈值进行了蒙特卡罗概率敏感性分析。
每年每挽救一年生命的增量成本效益比(ICER)随年龄和 BRCA2 突变状态的增加而增加,BRCA1 突变的年轻患者显示出更大的生存获益。40 岁 BRCA1 突变携带者延迟 5 年进行 RRM 与 5 个月的生命获益相关(ICER 为 72739 美元/年),而 60 岁 BRCA2 突变携带者与 0.8 个月的生命获益相关(ICER 为 334906 美元/年)。在所有情况下,RRM 与在卵巢癌诊断后 5-10 年内进行相比,乳腺癌预防的每例乳腺癌的成本效益最低。
对于大多数在诊断出卵巢癌后携带 BRCA1/2 突变的携带者而言,与乳腺癌筛查相比,在卵巢癌诊断后 5 年内进行 RRM 并不具有成本效益。在卵巢癌诊断后的最初几年中,应提倡进行影像学监测,此后可以根据患者年龄和 BRCA 突变状态考虑 RRM 的益处。