Fig 1

Flowchart showing an example of how the cumulative incidence of breast cancer and the three epidemiologic parameters are related. In this example, a hypothetical cohort of one million women is followed from age 20 to age 45. Overall, 11,900 cases of breast cancer are expected (cumulative incidence). Among these 11,900 women with breast cancer, 595 (5%) will have a BRCA1 or BRCA2 mutation (clinical sensitivity). When the penetrance estimate of 25% is applied, 2,380 women carry a mutation (595 / 0.25). Thus, 1,785 women with a mutation have not developed breast cancer by age 45 (2,380 − 595). The carrier rate is, therefore, 1 in 420. Numbers in the remaining boxes in Fig. 1 are computed by subtraction.