The High Risk Breast Cancer Gene: PALB2 - Pathway Genomics
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The High Risk Breast Cancer Gene: PALB2

If you have a strong family history of breast cancer but tested negative for BRCA1 and BRCA2, there’s another key gene you may want to have checked – PALB2. A study published in The New England Journal of Medicine found that women under 40 years old with mutations in the PALB2 gene may have 8-9 times higher risk of developing breast cancer during their lifetime as compared to the general population.

Researchers from the University of Cambridge examined genetic information from 362 participants from 154 different families to help us learn more about the PALB2 gene. Each participant had at least 1 family member with breast cancer, tested negative for mutations in the known BRCA1 and BRCA2 genes and have a mutation in PALB2. They identified 311 women with a PALB2 mutation and calculated the risk for mutation carriers. This study, along with many others, suggests PALB2 could be regarded as the 3rd most important genetic player, following BRCA1 and BRCA2, in breast cancer
susceptibility. Below are important things you should know about the PALB2 gene.

  • What does the name PALB2 mean?

    PALB2 stands for “Partner And Localizer of BRCA2”. As the name suggests, PALB2 interacts very closely with BRCA2, another key breast cancer susceptibility gene.
  • What is the normal function of the PALB2 gene and how does it play a role in cancer?

    The PALB2 gene has the genetic blueprint to make the PALB2 protein. The encoded protein interacts with other proteins, such as BRCA1 and BRCA2, to play essential roles in DNA damage repair pathways. These proteins work together to repair the broken strands of our DNA in a process called homologous recombination. Without PALB2, accumulation of the unrepaired DNA goes unchecked, leading to uncontrolled growth and proliferation of abnormal cells and increased risk for cancer.
  • Who may be at risk?

    Men and women who have a strong family history of breast cancer and/or pancreatic cancer could benefit from a discussion with their doctor or genetic counselor. Currently, the strongest supporting evidence regarding PALB2 points toward breast and pancreatic cancer susceptibility, although there are also a few reports suggesting links with ovarian cancer and prostate cancer.
  • What does it mean if I have tested positive for mutations in PALB2?

    Based on the new study in The New England Journal of Medicine, an estimated increased risk of breast cancer for female PALB2 mutation carriers was 14% by age 50 and 35% by 70. However, this number increases to 58% if you have a strong family history with two or more first-degree relatives with breast cancer. These numbers show an increased risk for breast cancer if a patient tests positive for PALB2 mutations as compared to the general population. If you have mutations in PALB2 they should be discussed with you doctor.


  1. Wojcik P, Jasiowka M, Strycharz E, et al. Recurrent mutations of BRCA1, BRCA2 and PALB2 in the population of breast and ovarian cancer patients in Southern Poland. Hereditary Cancer in Clinical Practice. 2016;14:5.
  2. Nguyen-Dumont T, Hammet F, Mahmoodi M, et al. Mutation screening ofPALB2 in clinically ascertained families from the Breast Cancer Family Registry.Breast cancer research and treatment. 2015;149(2):547-554.
  3. Antoniou AC, Casadei S, Heikkinen T, et al. Breast-Cancer Risk in Families with Mutations in PALB2The New England journal of medicine. 2014;371(6):497-506.