When hereditary breast and ovarian cancer (HBOC) due to a BRCA1/BRCA2 germline pathogenic variant is diagnosed, the proband will be asked to inform other at-risk family members. In the Netherlands, a guideline was introduced in 2012 which provided detailed recommendations regarding this proband-mediated procedure. We now evaluated the uptake of predictive BRCA1/BRCA2 testing in 40 consecutive HBOC families diagnosed in our centre in 2014. We performed a retrospective observational study of all 40 families in which a pathogenic BRCA1/BRCA2 germline variant was identified during 2014. We scored the uptake of predictive and confirmatory testing by the end of 2018 and explored factors associated with the level of uptake. Two families were excluded. In the remaining 38 families, among 239 family members ≥18 years at 50% risk of being a mutation carrier or at 25% risk if the family member at 50% risk was deceased, 102 (43%) were tested. Among 108 females 25–75 years of age at 50% risk, 59 (55%) underwent predictive or confirmatory testing, and among 43 males at 50% risk with daughters ≥18 years, 22 (51%) were tested. Factors which complicated cascade screening included family members living abroad, probands not wanting to share information and limited pedigree information. In conclusion, the standard proband-mediated procedure of informing relatives seems to be far from optimal. We suggest a tailored approach for each family, including the option of a direct approach to at-risk family members by the geneticist. In addition, we suggest detailed monitoring and follow-up of families.

当诊断出由BRCA1 / BRCA2种系致病性变异引起的遗传性乳腺癌和卵巢癌 (HBOC) 时，先证者将被要求通知其他有风险的家庭成员。荷兰于 2012 年推出了一项指南，提供了有关这种先证者调解程序的详细建议。我们现在评估了2014 年在我们中心诊断的 40 个连续 HBOC 家庭中预测性BRCA1/BRCA2检测的使用情况。我们对所有 40 个家庭进行了一项回顾性观察研究，其中有致病性BRCA1/BRCA2种系变异在 2014 年被发现。我们在 2018 年底对预测性和验证性测试的吸收进行了评分，并探索了与吸收水平相关的因素。两个家庭被排除在外。在其余 38 个家庭中，在 239 名≥18 岁的家庭成员中，有 50% 的风险是突变携带者，或者如果有 50% 风险的家庭成员已故，则有 25% 的风险，其中 102 名（43%）接受了检测。在风险为 50% 的 25-75 岁女性 108 名中，有 59 名（55%）接受了预测性或验证性测试，在 43 名风险为 50% 且女儿≥18 岁的男性中，22 名（51%）接受了检测。使级联筛查复杂化的因素包括居住在国外的家庭成员、不愿分享信息的先证者和有限的谱系信息。总之，标准的先证者介导的亲属通知程序似乎远非最佳。我们建议为每个家庭量身定制方法，包括选择由遗传学家直接处理高危家庭成员的方法。此外，我们建议对家庭进行详细的监测和随访。