Loss-of-function mutations in PALB2 are associated with an increased risk of breast cancer; however, the lifetime risk of this disease for women who have inherited PALB2 mutations is not known. Marc Tischkowitz and colleagues have now shown that the risk of breast cancer for PALB2 mutation carriers can be as high as the risk reported for BRCA2 carriers.

The investigators collected data on 362 individuals with PALB2 mutations from 154 eligible families, and used a modified segregation-analysis approach to determine the age-specific risk of breast cancer, considering the effects of PALB2 genotype and residual familial aggregation.

“This is by far the largest study to date and provides the most accurate risk estimates for PALB2 mutation carriers,” comments Tischkowitz. He continues, “we found that a woman with a PALB2 mutation has a 35% risk of developing breast cancer by the age of 70 years, rising to 58% if there is a strong family history.”

The researchers have also reported that the breast cancer risk associated with PALB2 mutation is higher in younger women (those born after 1960).

Although a large proportion of hereditary breast cancer cases remains unexplained, this study clearly confirms PALB2 as an important gene in this pathology, together with BRCA1 and BRCA2. Undoubtedly, “these results will help clinicians to better advise and manage those women with PALB2 mutations”, concludes Tischkowitz.