Why are the majority of hereditary cases of early-onset breast cancer sporadic? A simulation study

Abstract

Population-based studies, including those of Ashkenazi Jews, have observed that at least 50% of women with early-onset breast cancer who carry a germ line mutation in BRCA1 or BRCA2 do not report a family history of the disease. That is, the majority of 'hereditary' cases are 'sporadic.' Furthermore, the great majority of 'familial breast cancers' are not hereditary. We conducted a simulation study to evaluate the probability that a woman with early-onset breast cancer is a mutation carrier, given the number of affected relatives, for a range of plausible values of allele frequency (0.001-0.01), and increased risk in mutation carriers (5-20, equivalent to cumulative risks to age 70 of 25-70%..