BRCA1和BRCA2突变携带者双侧输卵管卵巢切除术后的死亡率：一项前瞻性队列研究。

Mortality after bilateral salpingo-oophorectomy in BRCA1 and BRCA2 mutation carriers: a prospective cohort study.

作者信息

Domchek Susan M, Friebel Tara M, Neuhausen Susan L, Wagner Theresa, Evans Gareth, Isaacs Claudine, Garber Judy E, Daly Mary B, Eeles Rosalind, Matloff Ellen, Tomlinson Gail E, Van't Veer Laura, Lynch Henry T, Olopade Olufunmilayo I, Weber Barbara L, Rebbeck Timothy R

机构信息

Abramson Cancer Centre, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6021, USA.

出版信息

Lancet Oncol. 2006 Mar;7(3):223-9. doi: 10.1016/S1470-2045(06)70585-X.

DOI:10.1016/S1470-2045(06)70585-X

PMID:16510331

Abstract

BACKGROUND

Bilateral prophylactic salpingo-oophorectomy (BPSO) is used widely used to reduce the risk of breast and ovarian cancer in women with BRCA1 and BRCA2 mutations. However, the reduction in mortality after this surgery is unclear. We aimed to assess whether BPSO improves overall mortality or cancer-specific mortality in BRCA1 and BRCA2 mutation carriers.

METHODS

We identified a prospective cohort of 666 women with disease-associated germline mutations in BRCA1 or BRCA2 and no previous cancer diagnosis. In our primary analysis, we compared 155 women who had had BPSO and 271 women matched for age at BPSO who had not had BPSO. In our secondary analysis, we compared 188 women who had had BPSO with 478 women who had not. In both analyses, we compared overall mortality and cancer-specific mortality. All analyses were adjusted for centre, mutation (BRCA1 vs BRCA2), and birth year.

FINDINGS

In the primary analysis, mean follow-up from BPSO to censoring was 3.1 years [SD 2.4] in the BPSO group and 2.1 years [2.0] in the non-BPSO group. The hazard ratio (HR) for overall mortality was 0.24 (95% CI 0.08-0.71), for breast-cancer-specific mortality was 0.10 (0.02-0.71), and for ovarian-cancer-specific mortality was 0.05 (0.01-0.46) for women who had BPSO compared with those who had not. In secondary analysis, BPSO was associated with reduced overall mortality (HR 0.28 [95% CI 0.10-0.74]), but not with breast-cancer-specific mortality (0.15 [0.02-1.18] or ovarian-cancer-specific mortality (0.23 [0.02-1.87]. When regarded as a time-dependent covariate, BPSO was not associated significantly with mortality.

INTERPRETATION

If confirmed, the finding that BPSO improves overall survival and cancer-specific survival in women with BRCA mutations will complement our existing knowledge of cancer-risk reduction associated with BPSO. Together, these data could give information to women who are considering genetic testing.

摘要

背景

双侧预防性输卵管卵巢切除术（BPSO）被广泛用于降低携带BRCA1和BRCA2突变女性患乳腺癌和卵巢癌的风险。然而，该手术后死亡率的降低情况尚不清楚。我们旨在评估BPSO是否能改善携带BRCA1和BRCA2突变女性的总体死亡率或癌症特异性死亡率。

方法

我们确定了一个前瞻性队列，其中有666名患有与疾病相关的BRCA1或BRCA2种系突变且既往未患癌症的女性。在我们的主要分析中，我们比较了155名接受BPSO的女性和271名在接受BPSO时年龄匹配但未接受BPSO的女性。在我们的次要分析中，我们比较了188名接受BPSO的女性和478名未接受BPSO的女性。在两项分析中，我们都比较了总体死亡率和癌症特异性死亡率。所有分析均针对中心、突变类型（BRCA1与BRCA2）和出生年份进行了调整。

研究结果

在主要分析中，BPSO组从手术到审查的平均随访时间为3.1年[标准差2.4]，非BPSO组为2.1年[2.0]。接受BPSO的女性与未接受BPSO的女性相比，总体死亡率的风险比（HR）为0.24（95%置信区间0.08 - 0.71），乳腺癌特异性死亡率的HR为0.10（0.02 - 0.71），卵巢癌特异性死亡率的HR为0.05（0.01 - 0.46）。在次要分析中，BPSO与总体死亡率降低相关（HR 0.28 [95%置信区间0.10 - 0.74]），但与乳腺癌特异性死亡率（0.15 [0.02 - 1.18]）或卵巢癌特异性死亡率（0.23 [0.02 - 1.87]）无关。当将BPSO视为时间依赖性协变量时，它与死亡率无显著关联。