To determine whether the BRCAX families might still contain important genetic subsets awaiting discovery will require prospective ascertainment of a large number of women with familial breast cancer who are screened for all currently established predisposition genes, whose tumours are assessed for multiple parameters in a uniform manner, and in which controls (BRCA1/2+ and non-familial 'sporadic' cases) are collected from the same population.
These findings introduce a new insight in the biology of hereditary breast cancer, defining specific BRCAX subgroups, which could help in the search for novel susceptibility pathways in hereditary breast cancer.
The aim of this study was to identify this phenotype amongst index cases from families in the kConFab familial breast cancer resource with no known pathogenic mutation ('BRCAX' families).
Mutations in the two known major breast cancer susceptibility genes, BRCA1 and BRCA2, account for a minority of familial breast cancer, whereas families without mutations in these genes (BRCAX group) account for 70% of familial breast cancer cases.