Study: Understanding inherited PALB2 mutations and risk of multiple cancers
Inherited mutations in the PALB2 gene are linked to increased risk of several cancers, including breast, pancreatic, ovarian, and prostate cancers. This study estimates the effect of an inherited PALB2 mutation on a person’s risk of developing each of these cancers. (posted 4/6/2026)
RELEVANCE
Most relevant for: People with a PALB2 mutation.
It may also be relevant for:
- people with a genetic mutation linked to cancer risk
Relevance: High
Strength of Science: High
Research Timeline: Post Approval
What is this study about?
This study looks at how having a mutation in the gene can increase a person's chances of getting breast, ovarian, pancreatic, or cancer. The researchers used very large groups of data to find out how common mutations are in people with these cancers.
This study looks at how having an inherited change (mutation) in the gene can affect a person’s chances of getting breast, ovarian, pancreatic, or cancer. The researchers used large groups of data to find out how common mutations are in people who have these cancers, and to estimate the risk of getting each cancer for people with a gene mutation.
Prior research has found that mutations are associated with an increased risk of breast, ovarian and pancreatic cancer. You can read more about these risks here. While prior research suggested there may be a link between cancer and mutations, it is not clear how much a mutation could increase risk.
This study offers new insight into how affects the risk of developing these four cancers.
Study approach & findings
This study used data from Ambry Genetics and the National Institutes of Health’s () All of Us research database.
Researchers focused on the genetic test results from 1 million people tested by Ambry Genetics and identified how many people were diagnosed with four specific cancers. They then focused on how many people had a mutation. They found that less than 1% of patients diagnosed with these cancers had a mutation.
- Among 357,109 people with breast cancer, 2,775 (0.79%) had a mutation.
- Among 37,468 people with ovarian cancer, 107 (0.30%) had a mutation.
- Among 22,112 people with pancreatic cancer, 163 (0.74%) had a mutation.
- Among 32,738 people with cancer, 151 (0.46%) had a mutation.
Those who had a mutation and a cancer diagnosis were then compared to the general population using ’s All of Us database.
Researchers note that these results confirmed the risk of these four cancers is increased among people with a mutation. People with the gene mutations are more likely to develop breast, ovarian, pancreatic and cancer than the general population.
- For breast cancer, the increased risk is associated with both and HR-negative breast cancers.
- Increased risk of breast cancer was seen across people of all racial and ethnic groups.
Some people with mutations developed more than one type of cancer. For example:
- One-third of the people with a mutation who were diagnosed with pancreatic cancer had previously been diagnosed with breast cancer.
- 13% of the people with a mutation who were diagnosed with ovarian cancer had previously been diagnosed with breast cancer.
- Pancreatic and cancers were also seen occurring together in some individuals.
This suggests that cancer survivors with a mutation may need more specific monitoring for more than one type of cancer.
What does this mean for me?
Most people are not routinely tested for or other genes linked to cancer unless they have a personal or family history of cancer. If you have reason to suspect that you may have a mutation in or another gene linked to cancer, talk with your doctor about genetic testing. Ideally, the first step will be a referral to a genetics professional who will gather information about your personal and family medical history and help you decide whether genetic testing is right for you. Discussions with your doctor or a genetic counselor will provide you with more information to help you make informed decisions about your health.
If you or a relative have been diagnosed with breast, ovarian, pancreatic, or cancer and have never had genetic testing, talk with your doctor about a referral to a genetics expert for genetic counseling and testing. If you had genetic testing in the past, before 2014, and tested negative for an , ask your doctor or genetic counselor if you might benefit from additional testing. Genetic testing has improved and many of the cancer genetic tests available before 2014 did not incude .
If you or someone in your family has been found to have a mutation in , this study offers more details about what this means for you and your relatives' risk of developing breast, ovarian, pancreatic, or cancer. Overall, this study helped to demonstrate that:
- A mutation in or any gene linked to cancer does not mean that you will develop cancer, but your risk of cancer is higher than average for these cancers.
- A mutation in means that your risk of breast, pancreatic, ovarian, and cancers is higher than the general population
If you have a mutation in , a doctor can help you determine next steps –specifically what kinds of screenings to have and when.
Reference
Tan YY, Hu C, Huang H, et al. Cancer-specific risks associated with PALB2 pathogenic variants from a large clinical genetic testing cohort. Presented by Y.Y. Tan at the 2025 San Antonio Breast Cancer Symposium on Friday, December 12.
Disclosure: FORCE receives funding from industry sponsors, including companies that manufacture cancer drugs, tests and devices. All XRAYS articles are written independently of any sponsor and are reviewed by members of our Scientific Advisory Board prior to publication to ensure scientific integrity.
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posted 4/6/2026
Questions To Ask Your Doctor
- I have a cancer diagnosis. Do you recommend genetic testing?
- If I test positive for an , will that change my treatment recommendations?
- If I test positive for an , what does it mean for my children, siblings, or other family members?
- I have a gene mutation. Which cancers should I be screened for, and how often should I be screened?
- For breast cancer screening, is a still the right screening for me, or should I consider an ?
- What kind of screenings are available for other cancers, and do they have an impact on health outcomes?
- If I test positive for , do you recommend that my relatives be tested too?
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