When it comes to genetic risk factors for breast cancer development, inherited mutations in the BRCA1 and BRCA2 genes garner all the attention. However, there are a great deal of other gene mutations that can also raise a woman’s breast cancer risk. Research conducted by the PALB2 Interest Group has revealed that one out of every three women carrying a mutation in the PALB2 gene are at risk for developing breast cancer by the time they reach the age of 70.

"Knowing the key genes that significantly increase cancer risk and having precise cancer risk estimates ultimately could help assess the breast cancer risk for each woman and allow better targeting or surveillance," Dr. Antonis Antoniou from the Centre for Cancer Genetic Epidemiology at the University of Cambridge said in a statement.

A research team from 17 centers in eight countries led by the University of Cambridge set to determine the breast cancer risk associated with what they called the most important breast cancer gene after BRCA1 and BRCA2. Their assessment included 154 families without a history of the BRCA1 or BRCA2 gene mutations, including 362 family members carrying the PALB2 gene mutation. Mutations in the PALB2 gene were first linked to breast cancer back in 2007, and it has been known to interact with the BRCA1 and BRCA2 genes.

Women carrying the PALB2 gene mutation had around a 35 percent chance of developing breast cancer by the age of 70. Each woman’s level of risk was determined by a family of history of breast cancer, so PALB2 carriers with more family members affected by breast cancer stood a higher risk. The research team called for more surveillance studies to discover the precise number of women who carry the PALB2 gene mutation. Similar to women carrying the BRCA1 and BRCA2 gene mutations, women with the PALB2 gene mutations born recently had a higher risk compared to women born earlier.

"We're learning all the time about the different factors that may influence a woman's chances of developing breast cancer,” said Professor Peter Johnson, Cancer Research UK's chief clinician. “This particular mutation doesn't make people certain to develop cancer, but it's another piece of information to help women make proper informed choices about how they may help to minimize their own risk."

According to the American Cancer Society, between five and 10 percent of all breast cancer diagnoses are considered hereditary. Families carrying the BRCA1 gene mutation can have an increased breast cancer risk of between 55 and 80 percent, while the risk associated with the BRCA2 gene mutation is estimated at around 45 percent. A new class of drugs being used to treat BRCA1/BRCA2-related breast cancer, PARP inhibitors, have also shown promise in reacting to cells carrying the PALB2 mutation.

"Since the BRCA1 and BRCA2 mutations were discovered in the mid-90s, no other genes of similar importance have been found and the consensus in the scientific community if more exist we would have found them by now,” added Dr. Marc Tischkowitz from the Department of Medical Genetics at the University of Cambridge. “PALB2 is a potential candidate to be 'BRCA3'. As mutations in this gene are uncommon, obtaining accurate risk figures is only possible through large international collaborations like this.”

Source: Antoniou A. et al. Inherited loss-of-function mutations in PALB2 and breast cancer risk. NEJM. 2014.