PALB2 is a gene that helps cells repair damaged DNA. People born with a harmful change in one copy of the PALB2 gene have a higher-than-average risk of breast cancer. They also have a small increase in the risk of ovarian cancer, pancreatic cancer, and breast cancer in men. There is no widely used syndrome name for this condition, so it is usually described as PALB2-associated cancer risk or PALB2 hereditary breast cancer risk.
This article is written for people who carry a PALB2 change, whether or not they have ever had cancer. Many readers learn they carry a PALB2 change after a relative tests positive, or from a genetic test ordered for another reason. Others learn it after a breast, ovarian, or pancreatic cancer diagnosis. No medication removes the inherited risk, but screening and preventive options can lower it.
This article explains what the PALB2 gene does, which cancers a PALB2 change increases the risk of, and how those risks are estimated. It also explains how PALB2 test results are reported, what screening and risk-reducing options are available, and what a result means for your family.
The PALB2 gene carries instructions for making a protein that repairs DNA breaks. Its name stands for “partner and localizer of BRCA2.” The PALB2 protein links the BRCA1 and BRCA2 proteins together and guides BRCA2 to the site of the damage. Together, they repair breaks that run through both DNA strands using a process called homologous recombination.
PALB2 is a tumor suppressor gene, meaning it normally protects cells from becoming cancer. Every cell has two copies of the gene, one from each parent. A person who inherits one changed copy still has one working copy, so their cells repair DNA normally. Cancer becomes more likely if the working copy is also damaged later in life, because that cell can no longer repair its DNA properly.
Because PALB2 works so closely with BRCA1 and BRCA2, its cancers overlap with those seen in hereditary breast and ovarian cancer syndrome; the risks are generally closer to BRCA2 than to BRCA1, and the ovarian cancer risk is lower than with either.
A harmful PALB2 change raises the risk of several cancers, but by very different amounts. Breast cancer in women is by far the most important. The risks below come mainly from a large international study of 524 families published in 2020. The general population figures are United States estimates from the American Cancer Society and the National Cancer Institute.
Without a strong family history, a woman who carries a PALB2 change has a lifetime breast cancer risk of about 1 in 3 to 1 in 2. For comparison, about 1 in 8 women (about 13 percent) in the general population develops breast cancer. Family history changes this figure substantially, as described in the next section.
The risk increases at younger ages. In the 2020 study, about 17 percent of women carrying a PALB2 change had developed breast cancer by age 50. Compared with other women their age, carriers in their twenties and thirties had a much higher relative risk than carriers in their seventies.
About 3 to 4 in 10 breast cancers in PALB2 carriers are triple-negative. This means the cancer cells lack estrogen receptors, progesterone receptors, and HER2. The others include estrogen receptor-positive cancers, the most common type of breast cancer overall. PALB2 carriers who have had breast cancer are also more likely to develop a new cancer in the other breast. Their risk is about two to three times that of other breast cancer survivors.
For women who carry a PALB2 change, the lifetime risk of ovarian cancer is about 3 to 5 percent by age 80. For comparison, about 1 in 91 women (about 1 percent) in the general population develops ovarian cancer. This is a real increase, but it is much smaller than the ovarian cancer risk linked to BRCA1 or BRCA2.
The risk stays low before age 50, at under 1 percent, and rises after that. When ovarian cancer does develop, it is usually high-grade serous carcinoma, the most common type. Women with two or more close relatives who had ovarian cancer have a higher risk, estimated at up to about 16 percent.
A PALB2 change causes a modest increase in the risk of pancreatic cancer. In the 2020 study, the lifetime risk by age 80 was about 2 percent for women and about 3 percent for men. Other studies have reported higher estimates, up to 5-10 percent. For comparison, about 1 in 56 to 1 in 60 people (a little under 2 percent) in the general population develops pancreatic cancer.
The type of pancreatic cancer linked to PALB2 is pancreatic ductal adenocarcinoma. A family history of pancreatic cancer raises the risk further. That family history is the main factor used to decide whether to offer screening.
Breast cancer is rare in men, but a PALB2 change makes it several times more likely. The lifetime risk for a man who carries a PALB2 change is about 1 percent by age 80. For comparison, about 1 in 755 men (about 0.1 percent) in the general population develops breast cancer. A man with breast cancer is usually offered genetic testing, and PALB2 is included on most panels.
Studies have not yet shown clearly whether a PALB2 change raises the risk of other cancers.
Breast cancer risk estimates for PALB2 carriers range widely, from about 1 in 3 to more than 3 in 4. The main reason is how participants were recruited. The earliest studies looked at families with many cases of breast cancer. Those families often share other genetic and lifestyle factors that also raise risk, so their estimates are higher than the risk for an average carrier.
Family history is the most important factor that changes an individual carrier’s risk.
Other factors also affect risk, including the age at which relatives were diagnosed, reproductive history, and breast density on mammograms. Risk calculators such as CanRisk combine these factors with the PALB2 result to give a personal estimate. Your genetics team can tell you which estimate fits your situation.
A high risk is not a certainty. Even at the upper estimates, some PALB2 carriers never develop breast cancer, and most never develop ovarian or pancreatic cancer. The breast cancer risk is high enough to justify starting screening early. It is not so high that cancer should be considered inevitable.
PALB2 testing is almost always done as part of a multi-gene panel rather than on its own. The same panel usually includes BRCA1, BRCA2, and other genes linked to breast, ovarian, and pancreatic cancer. Testing is commonly offered to people in these situations:
Testing criteria vary by country, health system, and insurer. A genetic counselor or genetics clinic can tell you whether testing is recommended for you.
Testing for an inherited PALB2 change uses a blood or saliva sample. The laboratory reads the DNA of the PALB2 gene and the other genes on the panel, usually using next-generation sequencing (NGS). Most laboratories also look for larger missing or extra pieces of the gene that sequencing can miss.
A genetics clinic or specialist usually arranges testing and discusses it with you beforehand. This discussion covers what the test can find, what each result would mean, and how a result could affect your relatives. Our article on genetic testing in cancer explains this process in more detail.
A PALB2 genetic test result falls into one of four categories. Each category leads to a different plan, so it is important to know which one appears on your report.
A positive PALB2 result means you carry a harmful change in one copy of the gene. Your risks of breast cancer, and to a lesser extent ovarian, pancreatic, and male breast cancer, are higher than average. A positive result does not mean you have cancer, and it does not mean you will develop it. It means you can plan screening and prevention around a known risk.
A negative PALB2 result can mean two quite different things.
Mixing up these two results is a common and important error. A person with an uninformative negative result who stops screening may lose protection they still need.
A PALB2 change can be germline or somatic, and the two have very different meanings for you and your family.
Tumor sequencing panels test the DNA of the cancer, not the DNA you were born with. A PALB2 change on a tumor report does not, by itself, mean the change is inherited. Confirming that requires a separate germline test on blood or saliva. Some PALB2 changes found on tumor tests do turn out to be inherited. If your tumor report lists a PALB2 change and nobody has discussed germline testing with you, you can ask whether it would be appropriate.
Screening and risk-reducing options for PALB2 carriers are based mainly on the NCCN Guidelines for Genetic/Familial High-Risk Assessment: Breast, Ovarian, Pancreatic, and Prostate (version 1.2027). Other countries have their own guidelines, which differ in some details. In most cases, the guidelines describe options to discuss rather than a single recommended course. Family history weighs heavily in deciding what fits each person.
Breast screening for women who carry a PALB2 change starts earlier and is more intensive than routine screening. The usual plan includes:
Screening may start earlier when a relative was diagnosed at a young age. Screening does not prevent breast cancer. Its purpose is to find cancer early, when treatment is most effective. Medications that block the effects of estrogen, such as tamoxifen, may also lower breast cancer risk, and your care team can discuss whether they suit you.
Risk-reducing mastectomy is surgery to remove both breasts before cancer develops. It lowers the risk of breast cancer by about 90 percent. Some breast tissue always remains, so the risk does not fall to zero. The operation has not been shown to extend life for PALB2 carriers beyond what careful screening does.
The changes after mastectomy are permanent. Breastfeeding is no longer possible. Chest skin sensation is usually reduced or lost, and the nipples may be removed. Many people choose reconstruction, which can mean more than one operation over time, while others choose not to have reconstruction.
Current guidelines do not set an age for this surgery for PALB2 carriers. Instead, they recommend discussing it, taking family history and personal preference into account. Yearly MRI and mammography are a genuine alternative. Its main limitation is that it finds cancer rather than preventing it, so some carriers on screening will still be diagnosed with breast cancer and need treatment. The choice is personal, and many people make it after meeting a genetic counselor and a breast surgeon.
There is no reliable screening test for ovarian cancer. Ultrasound and the CA-125 blood test have not been shown to find ovarian cancer early enough to save lives, so they are not recommended for routine screening of PALB2 carriers.
Risk-reducing salpingo-oophorectomy is surgery to remove both ovaries and fallopian tubes. For PALB2 carriers, current guidelines suggest discussing it from about age 45 to 50. This later timing reflects the lower ovarian cancer risk compared with BRCA1 and BRCA2. Some guidelines suggest basing the decision on an individual risk estimate that includes family history. Removing the uterus at the same time is optional, because PALB2 is not known to raise the risk of uterine cancer.
Removing the ovaries before natural menopause causes immediate menopause. This can bring hot flashes, sleep problems, vaginal dryness, and a higher long-term risk of bone thinning and heart disease. Pregnancy is no longer possible with your own eggs after the surgery. Hormone therapy can relieve many of these effects, and your care team can discuss whether it suits you. Removing the fallopian tubes first and delaying removal of the ovaries is being studied, but it is not yet proven for high-risk people.
Pancreatic cancer screening is offered to PALB2 carriers selectively, based on family history. For carriers with a parent, brother, sister, child, or other close relative who had pancreatic cancer, current guidelines suggest discussing screening from age 50. Screening may start 10 years before the youngest relative’s diagnosis if that is earlier.
Screening uses a yearly MRI of the pancreas, an endoscopic ultrasound, or both, at a center experienced in high-risk screening. For carriers without a family history of pancreatic cancer, the benefit of screening is less clear, and guidelines differ.
Men who carry a PALB2 change have a higher risk of breast cancer and possibly prostate cancer. Current guidelines suggest:
When cancer develops in a PALB2 carrier, the PALB2 result can affect treatment and risk. Cancer cells that have lost both working copies of PALB2 cannot repair DNA through homologous recombination. This weakness can make them more sensitive to platinum chemotherapy and to drugs called PARP inhibitors.
Drug approvals for PALB2 differ between countries and change over time. Approval also does not guarantee funding or availability. Your oncologist can tell you what applies to you.
Several other genes on a breast and ovarian cancer panel cause risks that overlap with PALB2. If you carry a change in one of them, the specific article for that gene will describe your risks more accurately.
An inherited PALB2 change is passed down in an autosomal dominant pattern. This means a person who carries the change has a 1 in 2 chance of passing it to each child, regardless of the child’s sex. Parents, brothers, sisters, and children of a carrier each have a 1 in 2 chance of carrying the same change. Men can carry and pass on a PALB2 change even if they never develop cancer themselves.
Once a PALB2 change has been found in one person, relatives can be tested for that exact change. This is called cascade testing. It is simpler and less expensive than the first test and provides a clear answer. Relatives who test negative for the family’s change have the same PALB2-related risk as anyone else. Many genetics clinics provide a family letter explaining the result for relatives to share with their doctors.
Testing for one PALB2 change is usually offered from age 18. The cancers linked to one PALB2 change rarely occur in childhood, and breast screening does not start until age 25 to 30. Waiting until adulthood also lets each person decide for themselves whether to be tested.
There is one important exception. A child who inherits a harmful PALB2 change from both parents develops a rare and serious condition called Fanconi anemia (type FA-N). This condition causes bone marrow failure, differences in growth and development, and cancers in early childhood. If both parents carry a harmful PALB2 change, each pregnancy has a 1 in 4 chance of Fanconi anemia. For this reason, a carrier who is planning a pregnancy may be offered testing for their partner. Some families, including those of Finnish and Polish ancestry, share specific PALB2 changes passed down over many generations.
After a positive PALB2 result, the next step is usually a visit with a genetic counselor or a high-risk clinic. That team can estimate your personal risk using your PALB2 result and family history, and plan screening at the right ages. They can also coordinate referrals to breast imaging, a breast surgeon, a gynecologist, or a pancreatic screening program as needed.
If you have been diagnosed with cancer, your PALB2 result may affect treatment choices, as described above. Your oncologist and surgeon will consider it alongside the findings on your pathology report. If you have not had cancer, your plan will focus on screening and on the timing of any preventive surgery you choose to consider.
Keep a copy of your genetic test report, including the exact name of the PALB2 change. Share it with every doctor who cares for you, and keep the genetics clinic informed of new cancers in your family. Our article What is a hereditary cancer syndrome? explains these steps for any inherited cancer risk.