Chai Xinglei, Friebel Tara M, Singer Christian F, Evans D Gareth, Lynch Henry T, Isaacs Claudine, Garber Judy E, Neuhausen Susan L, Matloff Ellen, Eeles Rosalind, Tung Nadine, Weitzel Jeffrey N, Couch Fergus J, Hulick Peter J, Ganz Patricia A, Daly Mary B, Olopade Olufunmilayo I, Tomlinson Gail, Blum Joanne L, Domchek Susan M, Chen Jinbo, Rebbeck Timothy R
Department of Biostatistics and Epidemiology, Center for Clinical Epidemiology and Biostatistics, The University of Pennsylvania School of Medicine, 2 Blockley Hall, 423 Guardian Drive, Philadelphia, PA, 19104-6021, USA.
Breast Cancer Res Treat. 2014 Nov;148(2):397-406. doi: 10.1007/s10549-014-3134-0. Epub 2014 Oct 14.
Inherited mutations in BRCA1 or BRCA2 (BRCA1/2) confer very high risk of breast and ovarian cancers. Genetic testing and counseling can reduce risk and death from these cancers if appropriate preventive strategies are applied, including risk-reducing salpingo-oophorectomy (RRSO) or risk-reducing mastectomy (RRM). However, some women who might benefit from these interventions do not take full advantage of them. We evaluated RRSO and RRM use in a prospective cohort of 1,499 women with inherited BRCA1/2 mutations from 20 centers who enrolled in the study without prior cancer or RRSO or RRM and were followed forward for the occurrence of these events. We estimated the age-specific usage of RRSO/RRM in this cohort using Kaplan-Meier analyses. Use of RRSO was 45% for BRCA1 and 34% for BRCA2 by age 40, and 86% for BRCA1 and 71% for BRCA2 by age 50. RRM usage was estimated to be 46% by age 70 in both BRCA1 and BRCA2 carriers. BRCA1 mutation carriers underwent RRSO more frequently than BRCA2 mutation carriers overall, but the uptake of RRSO in BRCA2 was similar after mutation testing and in women born since 1960. RRM uptake was similar for both BRCA1 and BRCA2. Childbearing influenced the use of RRSO and RRM in both BRCA1 and BRCA2. Uptake of RRSO is high, but some women are still diagnosed with ovarian cancer before undergoing RRSO. This suggests that research is needed to understand the optimal timing of RRSO to maximize risk reduction and limit potential adverse consequences of RRSO.
BRCA1或BRCA2(BRCA1/2)基因的遗传性突变会使患乳腺癌和卵巢癌的风险非常高。如果应用适当的预防策略,包括降低风险的输卵管卵巢切除术(RRSO)或降低风险的乳房切除术(RRM),基因检测和咨询可以降低这些癌症的风险和死亡率。然而,一些可能从这些干预措施中受益的女性并未充分利用它们。我们评估了来自20个中心的1499名携带BRCA1/2遗传性突变的女性的RRSO和RRM使用情况,这些女性在入组研究时没有既往癌症史或RRSO或RRM史,并对这些事件的发生进行了随访。我们使用Kaplan-Meier分析估计了该队列中RRSO/RRM的年龄特异性使用情况。到40岁时,BRCA1携带者的RRSO使用率为45%,BRCA2携带者为34%;到50岁时,BRCA1携带者为86%,BRCA2携带者为71%。估计BRCA1和BRCA2携带者到70岁时RRM使用率均为46%。总体而言,BRCA1突变携带者比BRCA2突变携带者更频繁地接受RRSO,但在BRCA2中,突变检测后以及1960年以后出生的女性中RRSO的接受率相似。BRCA1和BRCA2的RRM接受率相似。生育对BRCA1和BRCA2的RRSO和RRM使用均有影响。RRSO的接受率很高,但仍有一些女性在接受RRSO之前被诊断出患有卵巢癌。这表明需要进行研究以了解RRSO的最佳时机,以最大程度地降低风险并限制RRSO的潜在不良后果。