Having a family history of breast cancer nearly doubles a woman’s risk of developing the disease and genetic factors are known to play a major role in the origin of breast cancer.
The BRCA1 and BRCA2 genes were identified as major breast cancer susceptibility genes nearly 30 years ago and it is estimated that these gene mutations explain about 50 percent of familial breast cancer cases. BRCA1 and BRCA2 mutation tests have been widely used in high risk women (e.g., women with a strong family history of breast cancer) for risk assessment and management which may include prophylactic surgical and drug therapy intervention.
However, a significant fraction of familial breast cancer cases remain unexplained. A recent study identified the PALB2 gene as another major breast cancer predisposition gene. The PALB2 (Partner and localizer of BRCA2) gene produces a protein that is crucial for key BRCA2 functions. Mutation carriers of this gene were found to have a 35 percent risk of developing breast cancer by the age of 70, triple the risk seen in the general population. For breast cancer diagnosed before age 40, having PALB2 mutations was related to an 8 to 9-fold increased risk. It is estimated the PALB2 mutations explain about 2 to 3 percent of familial breast cancer risk. This study expanded our knowledge of genetic contributions to the familial profile of breast cancer.
Currently, the benefit and risk of deploying preemptive measures like surgery or drug therapy based on PALB2 mutation status is unknown. While the utility of applying PALB2 mutation information for risk management of high risk populations needs to be further investigated, individuals with known mutations of this gene are encouraged to seek genetic counseling because PALB2 mutations are also known to increase the risk of pancreatic cancer and may increase the risk of ovarian cancers. Mutations in PALB2 are very rare in the general population. Thus, screening for PALB2 in the general population appears to be unnecessary.
Xiao Ou Shu, M.D., Ph.D., MPH
Ingram Professor of Cancer Research
Vanderbilt-Ingram Cancer Center