Cancer Prevalence in 129 Breast-Ovarian Cancer Families Tested for BRCA1 and BRCA2 Mutations (Original Articles) (Report‪)‬

Breast cancer is the most common malignancy among women in South Africa, with a crude incidence rate of 18.5/100 000 recorded between 1993 and 1995. (1) A small but significant percentage (5-10%) of breast cancer cases are directly due to an inherited susceptibility. (2) Two tumour suppressor genes involved in early-onset breast and ovarian cancer, BRCA1 and BRCA2, have been mapped and cloned. (3,4) These two genes explain 20-40% of heritable breast cancer cases in various populations over the world. (5,6) A large linkage and mutation study on 237 families collected by the Breast Cancer Linkage Consortium found that overall BRCA1 accounts for 52% of all families, and BRCA2 for 32%, leaving 16% of the families with a familial breast cancer phenotype unaccounted for. (7) In the study, 81% of the families with both a breast and an ovarian phenotype were BRCA1-positive families while 14% linked to BRCA2. The situation was reversed in families that presented with a male breast cancer phenotype in addition to female breast cancer, where 76% linked to BRCA2 and only a small percentage to BRCA1. Worldwide many families with a strong history of familial breast cancer have been fully screened for BRCA1 and BRCA2 mutations but none were found. This is especially the case in breast cancer-specific families (no other cancers beside breast cancer in family). While the search for the BRCA1 and BRCA2 genes was helped by the strong association of ovarian cancer in addition to breast cancer with BRCA1 and male breast cancer with BRCA2, the search for other breast cancer-associated genes is more complicated. Studies on BRCA1- and 2-negative breast cancer families showed that the most probable explanation is that there are multiple additional genes with lower penetrance and/or prevalence, each responsible for a small number of families. (8,9)