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New Study Finds Mutations in PALB2 Gene Increase Lifetime Risk of Breast Cancer

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August 28, 2014

Researchers have found that another gene besides the more commonly discussed BRCA genes can have a significant impact on the risk of hereditary breast cancer. Specifically, inheriting a mutation in the PALB2 gene may increase the lifetime risk of developing breast cancer to 5 to 9 times that of women in the general population. However, more studies are likely needed before testing for PALB2 mutations might become routine.

Women with a family history of breast cancer may be familiar with BRCA mutations (see the BRCA1 and BRCA2 article). The PALB2 gene encodes a protein that helps to repair broken strands of DNA and prevent the buildup of genetic damage that can lead to uncontrolled cell growth and division. Certain mutations in PALB2 have been known to confer a predisposition to breast cancer, but the lifetime risk that those mutations confer had not been determined.

Recently, an international team of researchers performed a study to quantify this risk. The results of that study appear in the August 7, 2014 issue of the New England Journal of Medicine. The study analyzed breast cancer risk among 362 members of 154 families in which at least one person had breast cancer and a mutation in PALB2 but no BRCA mutations. Their data show that women with this gene mutation have an age- and family history-dependent breast cancer risk anywhere from 5 to 9 times as high as women in the general population. The absolute breast cancer risk by age 70 among women with PALB2 mutations ranged from 33% (among those with no family history of breast cancer) to 58% (among those who had at least two first-degree relatives with breast cancer at age 50) in this study.

Although PALB2 mutations are much rarer than BRCA mutations (only about 1% of breast cancer patients have a PALB2 gene mutation, according to the study's authors), the researchers conclude that PALB2 mutations are an important cause of hereditary breast cancer and that the risk associated with PALB2 mutations is great enough to justify adding genetic testing for such mutations to that for BRCA mutations. According to the National Cancer Institute, however, there is insufficient evidence at this time to support routine screening for PALB2 when tests for BRCA mutations are negative. More research is likely needed before national organizations may consider including such testing as part of their guidelines.

Women with a known family history of breast cancer may wish to discuss genetic testing for PALB2 mutations with their healthcare providers and consider consulting a genetic counselor to better understand the risks conferred by genetic mutations.

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(Modified July 11, 2014) National Cancer Institute Genetics of Breast and Ovarian Cancer PDQ®. Low- and Moderate-Penetrance Genes Associated With Breast and/or Ovarian Cancer. Available online at through Accessed August 2014.

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