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Another genetic mutation implicated in breast cancer risk

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It is well known that women who carry the BRCA1 or BRCA2 mutation are at increased risk for breast cancer. Now, a new study reports that another mutation in a gene known as PALB2 significantly increases a woman’s breast cancer risk. The findings were published on August 7 in The New England Journal of Medicine by researchers at the University of Cambridge in the United Kingdom.

The study authors note that previous research has reported that mutations in PALB2 were linked to breast cancer, and many genetic tests already screen for them. However, it is unclear to what degree these mutations increase a woman’s risk of developing the malignancy. Therefore, the investigators conducted a study of 362 members of 154 families with PALB2 mutations. None of the women carried the BRCA1 or BRCA2 mutations; however, all had at least one family member with breast cancer and a mutation in PALB2. There were 311 women with PALB2 mutations, among whom 229 had breast cancer, and 51 men with the mutation, of whom seven had the malignancy.

The investigators noted that, over all, a PALB2 mutation carrier had a 35% risk of developing breast cancer by age 70. This risk compared to a 50-70% risk among women with BRCA1 mutations and a 40-60% risk among women with BRCA2 mutations. These percentages are significantly higher than the lifetime risk for breast cancer in the general population, which stands at about 12%. In addition the researchers found that the breast cancer risk for women younger than 40 with a PALB2 mutation was eight to nine times higher than the general population. The risk was six to eight times higher among women aged 40 to 60 years with these mutations, and five times as higher among women older than 60 years.

The study authors could not explain why younger women with the mutation were at higher risk. Furthermore, the study comprised too few men with PALB2 mutations. In addition, the study found that women with the PALB2 mutations were slightly more likely to have “triple negative” breast cancer, which is a type of cancer that is resistant to hormonal treatment, more aggressive, and more likely to relapse than other types.

The researchers obtained their data from 14 sites in eight nations but found no significant geographic variations in its prevalence. They noted that larger studies are needed to determine such differences, as well as to assess the role of lifestyle and hormone use on breast cancer risk in PALB2 mutation carriers. Breast cancer risk is not only dependent on genetic factors but also on how the genes interact with the environment. For example, smoking increases breast cancer risk.

Take home message:

At present, breast cancer guidelines do not recommend screening for breast cancer genes in most women, only for those with a family history of the malignancy. Thus, if you have a family history of breast cancer, you should be tested for BRCA1, BRCA1, and PALB2 mutations.