PALB2 Mutation: A “New” Gene That Greatly Increases Breast Cancer Risk

Photo: Flickr/Micahb37

by Sarah Cortez

There’s been a recent surge in women asking for genetic testing for breast cancer, due in large part to Angelina Jolie’s public decision last year to get a prophylactic mastectomy after discovering she had a mutation in the BRCA1 gene. These days, another breast cancer gene has been making headlines, a gene called PALB2.

Mutations in BRCA1, and its related gene, BRCA2, are the two most important known genetic links to breast cancer risk. Well, new findings on PALB2 have some describing it as the “third gene” to be linked with breast cancer.

Previous studies have found that mutations in PALB2 combined with mutations in the BRCA genes increased the risk of breast cancer. PALB2 is even short for Partner and Localizer of BRCA2. What we didn’t know was how much the risk of breast cancer increased with a PALB2 mutation alone – that is without a related BRCA mutation.

In August, the New England Journal of Medicine published a study that characterized patients with only a PALB2 mutation. To do this, researchers identified patients who did not have a BRCA1/2 mutation but who had a history of breast cancer in at least one family member. These patients were then tested for the PALB2 mutation.

So, what did they find?

The results showed that a PALB2 mutation by itself increased the risk of breast cancer 9.5 times compared to the general population. They also showed that, for those with a mutation in PALB2, the risk of developing breast cancer by age 70 was about 33%, as compared to a 12% lifetime risk in the general population. Furthermore, for those with a PALB2 mutation who also had two first-degree relatives (like your mom and your sister) with breast cancer, the risk of developing breast cancer by age 70 increased to more than 50%. For comparison, a BRCA1 mutation increases your risk of developing breast cancer, by age 70, to 55-65%. So BRCA mutations are still considered more risky.

So what does all this new information mean to you?

Just like with the BRCA genes, it would only be recommended that you get screened for PALB2 mutation if you have a strong history of breast or ovarian cancer in your family, such as:

• Breast cancer in more than one family member

• Breast cancer diagnosed before the age of 50

• Breast cancer diagnosed in both breasts (bilateral breast cancer)

• Male breast cancer

• Breast cancer plus ovarian or pancreatic cancer

• Ashkenazi Jewish ethnicity

Many women at low risk for gene mutations are needlessly tested every year, which can cause a great deal of unnecessary anxiety.

If a woman tests positive for a BRCA mutation, we offer increased cancer screening, risk-reducing medications, prophylactic mastectomy, or some combination of these. While it’s likely such approaches will also help protect women with a PALB2 mutation, there is currently no evidence that they have benefit. More research is needed.

Genetic mutations like BRCA1/2 and PALB2 are frightening because they increase the risk of breast cancer by such a great degree. But it’s important to also keep in mind that they are rare. Around one in 400 women in the United States have a BRCA mutation, which translates to 0.25 percent of American women. And even women who have such mutations are not guaranteed to develop the disease.

For the large majority of women, the most important things they can do to improve their health and lower the risk of breast cancer is to focus on living an overall healthy lifestyle that includes: being physically active for at least 30 minutes a day, keeping weight in check, and drinking alcohol only moderately, if at all.