Breast Cancer Genetic Services in a South African Setting: Proband Testing, Cascading and Clinical Management

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.