The review of genetic screening services and common BRCA1/2 variants among South African breast cancer patients

Abstract

The South African genetic screening services for breast cancer comprise targeted and comprehensive tests that screen for the presence of genetic alterations. Clinically, these variants determine the risk of disease development as well as treatment approaches best suited for carriers. The current targeted tests screen for seven pathogenic sequence variants, which are mainly common among Whites, a population that constitutes 9.1% of South Africa. However, these tests are offered to all patients despite consistent negative results observed among Blacks, Indians, and Mixed ancestry (known as Coloreds in South Africa). Consequently, Blacks, White, and Colored patients who potentially carry other variants receive unbefitting treatment, resulting in poor clinical response, recurrence, and high mortality. This review aimed to identify the presence and incidence of pathogenic variants in BRCA1/2 previously reported in all South African populations. We selected literature using a scoping review approach, from which we included eight articles and two reports. Overall, we identified 59 BRCA1 and 60 BRCA2 pathogenic sequence variants from a cohort of 5709 patients and unknown patients from 90 families. The most reported variant was BRCA2 c.7943delG, which was common in White and Colored patients. None of the seven common variants was reported in either Blacks or Indians, which demonstrates the urgency to tailor genetic tests which are optimal for all South African patients and present a range of variants which could serve as diagnostic targets for Black, Indian, and Colored patients.

Navigating the genetic landscape of breast cancer in South Africa amidst a developing healthcare system

“…The selection of optimal test methods for breast cancer population-based testing presents one of the main controversies under current ethical debate. Genotyping is cost-effective but may miss rare variants, especially in diverse and understudied populations where founder variants contribute to <10% of the total mutation frequency ( Foulkes et al, 2016 ; Makhetha et al, 2023 ), preventing fair access to personalized treatment plans. However, a major benefit of a population-directed cost-effective portable POC genotyping assay together with innovative/alternative counseling models, is that it could enable screening in rural areas, which may increase access to genetic testing and improve primary care and cancer awareness in developing healthcare systems.…”

Navigating ethical challenges of integrating genomic medicine into clinical practice: Maximising beneficence in precision oncology

“…Ethics guidelines generally reflect a limited focus on ways to increase access to targeted therapies, such as Herceptin (Trastuzumab) and PARP inhibitors in Africa, with oncology clinical trials including genomic tests perceived as complex and requiring expensive technologies. Maketha et al [35] raised distributive justice concerns regarding BRCA1/2 founder/recurrent variant testing in SA, stemming from the historical interpretation of associated ancestral lineages as markers of race or ethnicity, leading to the direction of cost-effective genetic testing to specific population groups that benefited more than others. This aspect was addressed in the design of the rapid BRCA point-ofcare (POC) Research Assay evaluated by Mampunye et al, [24] which is applicable across the major ethnic groups in SA irrespective of age, family history or tumour type.…”