What It Means to Be PALB2-Positive, Plus What One Woman Did About It

The knowledge you get from genetic testing means you can make informed choices. This can lead to greater empowerment for you and your loved ones.

Mathilde Crutchfield, MD, always suspected she might be at risk for breast cancer. With a history of the disease in her family, she looked into genetic testing in her 20s. At the time, her doctor deemed her low risk and suggested she wait.

Fast-forward 20 years, the anesthesiologist and mother of three found herself in her new OB/GYN’s office going over her family medical history. Crutchfield explained that she’d lost her maternal grandmother and aunt to breast cancer as well as a cousin to ovarian cancer. That set off alarm bells for her doctor.

“They took another look at my family’s history and said, ‘This looks like a cluster,’” Crutchfield says. A cancer cluster is a greater-than-expected number of cancer cases in a particular community or locality.

So, Crutchfield decided to pursue genetic testing. While she was negative for BRCA mutations, which are often the culprit behind breast and ovarian cancers, she did test positive for the PALB2 mutation.

“Even with my family history, when I got that diagnosis, I went through a bit of a shock,” she says. “The irony of it was that had I been tested the first time in my 20s, I wouldn’t have gotten this diagnosis because PALB2 was not known then — it was discovered about 10 years ago.”

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What is PALB2?

PALB2 stands for Partner and Locator of BRCA2. It’s a gene that affects proteins that help repair damaged DNA. When the gene is mutated, it no longer functions normally and cannot help mend damaged cell DNA. This can lead to abnormalities in cells and, eventually, cancer.

According to 2014 research, women who have the PALB2 gene mutation are 35% more likely to develop breast cancer by age 70. PALB2 mutations may also put carriers at greater risk of ovarian and pancreatic cancers, although more research is needed to better understand the risk.

Though the PALB2 mutation is related to the BRCA2 gene, a 2015 study notes that mutations of both in one person are rare.

How are PALB2 mutations inherited?

Similar to BRCA1 and 2 mutations, PALB2 mutations are passed on to children from their parents. For those who carry the mutation, their biological parents, siblings, and children have a 50% chance of also having the mutation.

If both parents have a PALB2 mutation, which is rare, there’s a chance their children could be born with a condition called Fanconi syndrome (FS). Also associated with BRCA2 mutations, FS can cause birth defects and bone marrow failure, as well as increased cancer risk.

How are PALB2 mutations diagnosed?

Testing for the PALB2 gene mutation has only been available since 2014. Based on a patient’s family history, a doctor may order genetic testing to potentially identify mutations such as PALB2 or BRCA1 or 2.

In general, testing for PALB2 is done via a blood test that analyzes a panel of genes for potential mutations. In Crutchfield’s case, she received the Myriad Genetics MyRisk Hereditary Cancer Test. The test scanned a panel of 48 genes connected to more than a dozen cancers, from breast and ovarian to colorectal and endocrine.

Those who were tested for genetic mutations prior to 2014 may consider retesting, as their results would not have included PALB2.

What happens after a PALB2 diagnosis?

Once a patient receives a PALB2 mutation diagnosis, there are several different ways to proceed. Some may opt to do nothing, while others choose to pursue a more stringent screening regimen with ultrasounds, mammograms, and other tests to detect breast cancer.

“It is an absolutely personal decision,” Crutchfield says. “But what I do feel strongly about advocating for is that knowledge is power. Getting genetic testing and finding out if you have the gene mutation or not is so important.”

After consulting with her doctor and taking her family history into account, Crutchfield made the decision to have a preventive mastectomy to reduce her chance of developing breast cancer.

“We have all these different ways to detect breast cancer, and they’re all very good, but we only have one way to prevent it, and that’s surgery. And that was what stuck with me,” she says. “That’s the pragmatic, intellectual part of making the decision. But the emotional part of deciding to have surgery when you are healthy is still scary.”

Crutchfield also made the decision to have a prophylactic oophorectomy, or surgery to remove the ovaries and fallopian tubes, due to her history of ovarian cancer. A 2021 study showed a slight increase in ovarian cancer risk for those with PALB2 gene mutations.

“I wanted to be proactive, especially given that for ovarian cancer, the detection tools are not as good,” she says. “There are blood tests and ultrasounds, but often when it’s found, it’s a little bit later-stage. So even though the risk could be lower, the detection tools weren’t as good as they are for breast cancer.”

Making these decisions after a PALB2 diagnosis can be difficult, so it’s important to consult with your doctor to make the best choice for your particular case. You may also find preoperative counseling and support groups helpful.

The bottom line

For those with a history of breast or ovarian cancers in their family, genetic testing can be a powerful tool in preventing disease or getting an earlier diagnosis.

While the decisions made after a PALB2 mutation diagnosis may be difficult, Crutchfield says the ability to make more informed choices about her health far outweighed the fear of getting tested.

“Knowledge is power,” she says. “We have this ability to give you this knowledge so that you can exercise choices, and I think that’s where empowerment comes from. You don’t have to feel helpless.”