PurposeBRCA1/BRCA2 predictive test negatives are proven noncarriers of a BRCA1/BRCA2 mutation that is carried by their relatives. The risk of developing breast cancer (BC) or epithelial ovarian cancer (EOC) in these women is uncertain. The study aimed to estimate risks of invasive BC and EOC in a large cohort of BRCA1/BRCA2 predictive test negatives.MethodsWe used cohort analysis to estimate incidences, cumulative risks, and standardized incidence ratios (SIRs).ResultsA total of 1,895 unaffected women were eligible for inclusion in the BC risk analysis and 1,736 in the EOC risk analysis. There were 23 incident invasive BCs and 2 EOCs. The cumulative risk of invasive BC was 9.4% (95% confidence interval (CI) 5.9-15%) by age 85 years and the corresponding risk of EOC was 0.6% (95% CI 0.2-2.6%). The SIR for invasive BC was 0.93 (95% CI 0.62-1.40) in the overall cohort, 0.85 (95% CI 0.48-1.50) in noncarriers from BRCA1 families, and 1.03 (95% CI 0.57-1.87) in noncarriers from BRCA2 families. The SIR for EOC was 0.79 (95% CI 0.20-3.17) in the overall cohort.ConclusionOur results did not provide evidence for elevated risks of invasive BC or EOC in BRCA1/BRCA2 predictive test negatives.Genetics in Medicine advance online publication, 22 March 2018; doi:10.1038/gim.2018.44.

中文翻译：

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BRCA1 或 BRCA2 预测性测试阴性中乳腺癌或卵巢癌的风险：EMBRACE 研究的结果。

目的 BRCA1/BRCA2 预测性测试阴性被证明是其亲属携带的 BRCA1/BRCA2 突变的非携带者。这些女性患乳腺癌 (BC) 或上皮性卵巢癌 (EOC) 的风险尚不确定。该研究旨在评估 BRCA1/BRCA2 预测性检测阴性的大型队列中侵袭性 BC 和 EOC 的风险。方法我们使用队列分析来估计发病率、累积风险和标准化发病率 (SIR)。结果共有 1,895 名未受影响的女性符合条件BC 风险分析和 EOC 风险分析中的 1,736 个。有 23 例侵袭性 BC 和 2 例 EOC。到 85 岁时，侵袭性 BC 的累积风险为 9.4%（95% 置信区间 (CI) 5.9-15%），而 EOC 的相应风险为 0.6%（95% CI 0.2-2.6%）。侵袭性 BC 的 SIR 为 0.93 (95% CI 0.62-1. 40) 在整个队列中，来自 BRCA1 家族的非携带者为 0.85 (95% CI 0.48-1.50)，来自 BRCA2 家族的非携带者为 1.03 (95% CI 0.57-1.87)。在整个队列中，EOC 的 SIR 为 0.79 (95% CI 0.20-3.17)。结论我们的结果没有提供证据表明 BRCA1/BRCA2 预测性检测阴性中侵袭性 BC 或 EOC 风险升高。医学遗传学提前在线出版，3 月 22 日2018; doi:10.1038/gim.2018.44。