Centre for Health Informatics, Institute of Population Health, The University of Manchester, Jean McFarlane Building, Oxford Road, Manchester, M13 9PL, UK.
Breast Cancer Res Treat. 2013 Dec;142(3):611-8. doi: 10.1007/s10549-013-2765-x. Epub 2013 Nov 20.
The aim of this study was to establish if risk-reducing surgery (RRS) increases survival among BRCA1/2 carriers without breast/ovarian cancer at the time of family referral. Female BRCA1/2 carriers were identified from the Manchester Genetic Medicine Database. Those patients alive and unaffected at the date of first family ascertainment were included in this study. Female first-degree relatives (FDRs) without predictive genetic testing who otherwise met eligibility criteria were also included. The effect of breast and ovarian RRS on survival was analysed. The survival experiences of RRS and non-RRS patients, stratified by BRCA status, were examined with Kaplan-Meier curves and contrasted using log-rank tests and Cox models. 691 female BRCA1/2 mutation carriers without breast or ovarian cancer at time of family ascertainment were identified; 346 BRCA1 and 345 BRCA2. 105 BRCA1 carriers and 122 BRCA2 carriers developed breast cancer during follow-up. The hazard of death was statistically significantly lower (P < 0.001) following RRS versus no RRS. 10-year survival for women having RRS was 98.9 % (92.4-99.8 %) among BRCA1 and 98.0 % (92.2-99.5 %) among BRCA2 carriers. This survival benefit with RRS remained significant after FDRs were added. Women who had any form of RRS had increased survival compared to those who did not have RRS; a further increase in survival was seen among women who had both types of surgery. However, formal evidence for a survival advantage from bilateral mastectomy alone requires further research.
本研究旨在确定在家族转诊时，无乳腺癌/卵巢癌的 BRCA1/2 携带者的风险降低手术（RRS）是否能提高生存率。从曼彻斯特遗传医学数据库中确定了女性 BRCA1/2 携带者。在首次家族确定日期仍存活且未受影响的患者被纳入本研究。符合条件但未经预测性基因检测的女性一级亲属（FDR）也被纳入。分析了乳房和卵巢 RRS 对生存的影响。通过 Kaplan-Meier 曲线和对数秩检验和 Cox 模型分析了 RRS 和非 RRS 患者的生存经验，按 BRCA 状态分层。在家族确定时无乳腺癌或卵巢癌的 691 名女性 BRCA1/2 突变携带者被确定；BRCA1 为 346 名，BRCA2 为 345 名。在随访期间，105 名 BRCA1 携带者和 122 名 BRCA2 携带者发生了乳腺癌。与无 RRS 相比，RRS 后的死亡风险显著降低（P < 0.001）。进行 RRS 的女性的 10 年生存率为 BRCA1 携带者的 98.9%（92.4-99.8%），BRCA2 携带者的 98.0%（92.2-99.5%）。在纳入 FDR 后，这种 RRS 带来的生存获益仍然显著。与未接受 RRS 的女性相比，接受任何形式的 RRS 的女性的生存率更高；在接受两种手术的女性中，生存率进一步提高。然而，单侧乳房切除术单独带来生存优势的正式证据需要进一步研究。
