Study Suggests PALB2 Mutations Greatly Increase Chance of Getting Breast Cancer

Breast Cancer News
September 5, 2014
Erin Rowley, Writer and Content Coordinator
Reviewed By: 
Mary B. Daly, MD, PhD

Findings about the influence of PALB2 gene mutations on the risk of developing breast cancer could influence genetic testing. They could also affect the way people with a mutation on this gene make treatment decisions in the future.

Background and Goals

People who have a family history of breast cancer often get genetic testing, which gives them more information about their inherited risk of the disease. Doctors know a lot about genes called BRCA1 and BRCA2. These genes help repair damaged cells. When certain mutations, changes in the makeup of a cell, appear on these genes, it can greatly increase a person’s risk of getting breast cancer. In an  LBBC webinar, Dr. Jennifer R. Klemp said women with BRCA mutations can have a 45 to 85 percent chance of getting breast cancer by age 70. The risk in the general population is about 12 percent.

Harmful mutations on other genes can also increase the risk of getting breast cancer, but doctors don’t know as much about them. Because of that lack of knowledge, doctors don’t often test for those gene mutations, because they don’t know how the test results would affect a person’s treatment or risk of disease.

One of these other genes is called PALB2. It works with the BRCA genes to repair damaged cells. Past studies have found that PALB2 mutations increase a person’s risk of breast cancer by two to four times, compared to people who don’t have a mutation. That would make it a moderate-risk gene mutation, as opposed to BRCA, which is a high-risk gene mutation. These researchers wanted to learn more.


The team looked at 154 families in which at least one person had breast cancer and a PALB2 mutation, but had tested negative for BRCA1 and BRCA2 mutations.

The families included:

  • 311 women with PALB2 mutations, 229 of whom had breast cancer
  • 51 men with PALB2 mutations, 7 of whom had breast cancer

The number of family members who developed cancer and the pattern in which they developed it was used to estimate the risk of cancer for family members who had a harmful PALB2 mutation.


Findings suggest women with a PALB2 mutation have a 33 to 58 percent chance of getting breast cancer by age 70, depending on their family history. Compared to the general population, their risk is:

  • 8 to 9 times higher at age 40 and below
  • 6 to 8 times higher from ages 40 to 60
  • 5 times higher at age 60 and above

The researchers also believe about 2.4 percent of breast cancer found in family groups may be due to the PALB2 mutation, but more study is needed.

What This Means for You

You may have had genetic testing in the past and been told that you don’t have a mutation that completely explains your family history of breast cancer. Or, a family member may have tested negative for BRCA mutations, making it unnecessary for you to have testing yourself.

Asking your doctor whether your test included PALB2 or if you should be tested again for a mutation on this gene could lead to information that may affect your treatment decisions.

The mutations mentioned here are not the only ones that could explain a family history of breast cancer. As more research is done, doctors will better understand which gene mutations could increase your risk, and by how much.

If you’re interested in participating in a clinical trial on this subject, talk to your doctor and visit to see which trials are recruiting participants.

For more information about how your genes can affect your risk of breast cancer, read our  Guide to Understanding Genetics and Family Risk Assessment.

Antoniou, Antonis, Casadei, Silvia, Heikkinen, Tuomas et al.  Breast-Cancer Risk in Families with Mutations in PALB2The New England Journal of Medicine. August 7, 2014; doi: 10.1056/NEJMoa1400382.

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Genetic Tests
Clinical Trials