Newly Discovered Gene Mutation Raises Breast Cancer Risk

Mutations in two genes, BRCA1 and BRCA2, were known to raise a woman's risk of breast cancer long before Angelina Jolie’s now famous double mastectomy. But now, mutations in a third gene called PALB2 have been shown to increase breast cancer risk by almost as much.

In a recent study published in the New England Journal of Medicine, researchers from the University of Cambridge and the PALB2 Interest Group report their findings on the link between PALB2 and breast cancer. Women with PALB2 mutations have a 35 percent chance of developing breast cancer by age 70. If there is also a strong family history of the disease, their risk rises to 58 percent by age 70.

“It is by far the largest study to date and provides the most accurate risk estimates for PALB2 mutation carriers,” study co-author Dr. Marc Tischkowitz, of the University of Cambridge, told Healthline“It shows that the breast cancer risk is modified by the family history,” he said. Women who carried the PALB2 gene mutation and also had relatives diagnosed with breast cancer ran a much higher risk.

Learn More About the Causes of (and Risk Factors for) Breast Cancer »

Before this study, scientists didn't know the extent of the risk associated with a PALB2 gene mutation. “The PALB2 gene was first identified in 2006 and linked to breast cancer in 2007, but until now we have not had good breast cancer risk estimates for women who have inherited PALB2 mutations,” Tischkowitz said.

The risk associated with BRCA1 and BRCA2 mutations has been more thoroughly studied. Women who inherit a BRCA1 mutation have a 55 to 65 percent chance of developing breast cancer by age 70, and those who inherit a BRCA2 mutation have about a 45 percent chance, according to the National Cancer Institute (NCI). In the general U.S. population, 12 percent of women will develop breast cancer at some point during their lives, the NCI also reports.

“This is another piece of the puzzle in inherited breast cancers, and it puts PALB2 firmly on the map as an important breast cancer gene after BRCA1 and BRCA2.” — Dr. Marc Tischkowitz

Women who carry PALB2 mutations have a breast cancer risk eight to nine times higher than for women in the general population, the study authors say.

“This is another piece of the puzzle in inherited breast cancers, and it puts PALB2 firmly on the map as an important breast cancer gene after BRCA1 and BRCA2,” Tischkowitz said.

Researchers studied 154 families with 362 members who had PALB2 mutations. None of the family members carried BRCA1 or BRCA2 mutations. Of the 311 women in the study with PALB2 mutations, 229 developed breast cancer.

Find Out More About Your Genetic and Genomic Risk Factors »

These findings help clarify the picture for women who inherit PALB2 mutations. Doctors may now be able to recommend increased breast cancer screenings to women with inherited mutations. They can also offer genetic testing to their relatives to see if they have also inherited the mutation.

Researchers at a hospital in Cambridge University’s NHS Hospitals Trust have developed a clinical test for PALB2, which will eventually be available in diagnostic laboratories around the world.

“PALB2 mutations are much less common than BRCA1 or BRCA2, but as this gene is now routinely tested for as part of the breast cancer gene panels, it is likely that we are going to see an increase in the number of women who are found to be carriers for PALB2 mutations,” Tischkowitz said. The big picture of inherited breast cancer risk will become easier to see as more people get tested for PALB2 and researchers collect more data.

“A large proportion of hereditary breast cancer still remains unexplained,” Tischkowitz said. “But with ever more powerful gene sequencing techniques and ever larger international collaborations we expect that further significant advances will be made in this field in the coming years.”

Get Tested: See Which Screening Tests Are Available for Breast Cancer »