Department of Medical Oncology, Erasmus MC Cancer Institute, PO Box 5201, 3008 AE, Rotterdam, The Netherlands.
Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
Breast Cancer Res Treat. 2019 Oct;177(3):723-733. doi: 10.1007/s10549-019-05345-2. Epub 2019 Jul 13.
In healthy BRCA1/2 mutation carriers, bilateral risk-reducing mastectomy (BRRM) strongly reduces the risk of developing breast cancer (BC); however, no clear survival benefit of BRRM over BC surveillance has been reported yet.
In this Dutch multicenter cohort study, we used multivariable Cox models with BRRM as a time-dependent covariable to estimate the associations between BRRM and the overall and BC-specific mortality rates, separately for BRCA1 and BRCA2 mutation carriers.
During a mean follow-up of 10.3 years, 722 out of 1712 BRCA1 (42%) and 406 out of 1145 BRCA2 (35%) mutation carriers underwent BRRM. For BRCA1 mutation carriers, we observed 52 deaths (20 from BC) in the surveillance group, and 10 deaths (one from BC) after BRRM. The hazard ratios were 0.40 (95% CI 0.20-0.90) for overall mortality and 0.06 (95% CI 0.01-0.46) for BC-specific mortality. BC-specific survival at age 65 was 93% for surveillance and 99.7% for BRRM. For BRCA2 mutation carriers, we observed 29 deaths (7 from BC) in the surveillance group, and 4 deaths (no BC) after BRRM. The hazard ratio for overall mortality was 0.45 (95% CI 0.15-1.36). BC-specific survival at age 65 was 98% for surveillance and 100% for BRRM.
BRRM was associated with lower mortality than surveillance for BRCA1 mutation carriers, but for BRCA2 mutation carriers, BRRM may lead to similar BC-specific survival as surveillance. Our findings support a more individualized counseling based on BRCA mutation type.
在健康的 BRCA1/2 突变携带者中,双侧预防性乳房切除术(BRRM)可显著降低乳腺癌(BC)的发病风险;然而,目前尚未报道 BRRM 相较于 BC 监测在生存获益方面的优势。
本项荷兰多中心队列研究采用多变量 Cox 模型,以 BRRM 作为时依协变量,分别评估 BRCA1 和 BRCA2 突变携带者中 BRRM 与总体和 BC 特异性死亡率之间的相关性。
在平均 10.3 年的随访期间,1712 名 BRCA1(42%)和 1145 名 BRCA2 突变携带者中有 722 名(42%)和 406 名(35%)接受了 BRRM。BRCA1 突变携带者中,监测组有 52 例死亡(20 例死于 BC),BRRM 组有 10 例死亡(1 例死于 BC)。总死亡率的风险比为 0.40(95%CI 0.20-0.90),BC 特异性死亡率的风险比为 0.06(95%CI 0.01-0.46)。BC 特异性生存至 65 岁时,监测组为 93%,BRRM 组为 99.7%。BRCA2 突变携带者中,监测组有 29 例死亡(7 例死于 BC),BRRM 组有 4 例死亡(无 BC)。总死亡率的风险比为 0.45(95%CI 0.15-1.36)。BC 特异性生存至 65 岁时,监测组为 98%,BRRM 组为 100%。
与监测相比,BRRM 可降低 BRCA1 突变携带者的死亡率,但对于 BRCA2 突变携带者,BRRM 可能导致与监测相似的 BC 特异性生存。我们的研究结果支持基于 BRCA 突变类型进行更个体化的咨询。