PALB2 Mutations Confer Similar Breast Cancer Risk as BRCA2

On Aug. 6, 2014 researchers announced in The New England Journal of Medicine (N. Engl. J. Med 2014;371:497-506) that they had found that mutations in a gene called PALB2 greatly increase the risk of breast cancer.  Women harbouring a loss-of-function mutation in the PALB2 gene demonstrated an increased risk of developing breast cancer that was similar to the predisposition seen with mutations in the infamous BRCA2 gene. This is one of the biggest developments since the discovery in the ’90s of the role of mutations in the BRCA1 and BRCA2 genes in breast and ovarian cancer.  According to the New England Journal of Medicine study, by Marc Tischkowitz at the University of Cambridge and others, patients with a broken PALB2 gene and no family history of breast cancer have a 35 percent chance of developing breast cancer, but if they had two or more family members with cancer, the risk rises to 58 percent. The estimated cumulative risk of breast cancer for female PALB2 mutation carriers was 14% by age 50 and 35% by 70, representing a significant increase over the general population. The relative risk associated with PALB2 mutations was 8 to 9 in individuals below age 40, 6 to 8 for those between 40 and 60, and approximately 5 for those 60 and older. In general, the risk of developing breast cancer by age 70 for women with a mutation in BRCA1 or BRCA2 is approximately 60% and 45%, according to the National Cancer Institute. This is significant when you’re considering life-altering preventive surgery or screenings. The PALB2 gene codes the PALB2 protein that interacts with BRCA2 allowing it to connect with BRCA1, forming the BRCA complex