Osler T S, Schoeman M, Edge J, Pretorius W J S, Rabe F H, Mathew C G, Urban M F
Sydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
Division of Human Genetics, National Health Laboratory Service and School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
Cancer Med. 2025 Mar;14(5):e70743. doi: 10.1002/cam4.70743.
Limited data exist on managing hereditary breast cancer in low- middle-income countries (LMICs). We assessed proband and cascade genetic testing, and risk-reducing measures in a South African regional breast cancer service.
We analysed records from 534 consecutive female probands receiving genetic counselling for breast cancer and their 115 relatives who attended genetic counselling. Demographic and clinical data, family pedigrees and genetic test data were collated from hospital clinical records, regional laboratory data, screening appointments and radiological records.
Test uptake in probands was high (86.9%), although cost was a deterrent in some. There were 83 (19.6%) probands who tested positive, and 45.0% of them had one or more family members have testing. This resulted in 9.2% of relatives (first- to third-degree) having cascade testing. Family testing was associated with a stronger family history of cancer, female gender and being a first-degree relative (uptake was 25.6% in female first-degree relatives). Risk-reducing mastectomy was accepted by 52.6% of eligible female family members, while mammographic surveillance (30%) and bilateral salpingo-oophorectomy (15.4%) were less frequent.
Genetic testing was well accepted by probands, but uptake was low in family members. Overall, one family member carrying a pathogenic variant was identified for every 13 probands receiving genetic counselling and for every 11 probands tested. Risk-reducing measures were taken up by over half of those eligible. Limited uptake of cascade testing and variable uptake of risk-reducing options impacted the programme. To our knowledge, this is the first study in Africa of the real-world effectiveness of a breast cancer genetic service.
关于在低收入和中等收入国家（LMICs）管理遗传性乳腺癌的数据有限。我们评估了南非一个地区乳腺癌服务机构中先证者及级联基因检测情况，以及降低风险的措施。
我们分析了534名连续接受乳腺癌遗传咨询的女性先证者及其115名接受遗传咨询的亲属的记录。从医院临床记录、地区实验室数据、筛查预约和放射学记录中整理了人口统计学和临床数据、家族谱系及基因检测数据。
先证者的检测接受率较高（86.9%），尽管费用对一些人有阻碍作用。有83名（19.6%）先证者检测呈阳性，其中45.0%的人有一名或多名家庭成员进行了检测。这导致9.2%的亲属（一级至三级）进行了级联检测。家族检测与更强的癌症家族史、女性性别以及是一级亲属有关（女性一级亲属的接受率为25.6%）。52.6%符合条件的女性家庭成员接受了降低风险的乳房切除术，而乳房X线筛查（30%）和双侧输卵管卵巢切除术（15.4%）的频率较低。
先证者对基因检测接受度良好，但家庭成员的接受率较低。总体而言，每13名接受遗传咨询的先证者和每11名接受检测的先证者中，有一名携带致病变异的家庭成员被识别出来。超过一半符合条件的人采取了降低风险的措施。级联检测接受率有限以及降低风险方案的接受情况不一，影响了该项目。据我们所知，这是非洲第一项关于乳腺癌基因服务实际效果的研究。
