PALB2 mutations and breast cancer risk

In their article in the NEJM Antoniou et al report the risk of breast cancer among 362 members of 154 families who had deleterious truncating, splice, or deletion mutations in PALB2.

The risk of breast cancer for female PALB2 mutation carriers, as compared with the general population, was eight to nine times as high among those younger than 40 years of age, six to eight times as high among those 40 to 60 years of age, and five times as high among those older than 60 years of age. The estimated cumulative risk of breast cancer among female mutation carriers was 14% by 50 years of age and 35% by 70 years of age. Breast-cancer risk was also significantly influenced by birth cohort and by other familial factors. The absolute breast-cancer risk for PALB2 female mutation carriers by 70 years of age ranged from 33% for those with no family history of breast cancer to 58% for those with two or more first-degree relatives with breast cancer at 50 years of age.

The authors concluded loss-of-function mutations in PALB2 are an important cause of hereditary breast cancer.