PALB2 is not as well known as BRCA, but mutations of the gene can raise a woman’s risk for breast cancer almost as much.,


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For years, women with breast cancer in their families have been getting tested for mutations in two genes, known as BRCA1 and BRCA2, to determine whether they have a sharply elevated risk of the disease.

Now, doctors are increasingly recommending that anyone who was tested before 2014 go through genetic testing again — to look for a different mutation, one much less widely known.

It’s on a gene called PALB2, and people who have the mutation have almost as great a risk of getting breast cancer as those who have the BRCA mutations. Like the BRCA mutations, this mutation also increases a patient’s risk of ovarian and pancreatic cancer.

Anyone who gets a genetic test for breast cancer now will likely be screened for PALB2 mutations, which were found in 2014 to significantly raise breast cancer risk. But many patients screened before 2014 were not tested for it and may have a false sense of security if they were found to be free of the BRCA mutations, breast cancer experts said.

Even now, few patients have heard of the gene, while BRCA is familiar to many.

“Hereditary breast cancer risk assessment needs to go beyond BRCA1 and BRCA2 and include genes like PALB2,” said Dr. Peter Hulick, medical director of the Mark R. Neaman Center for Personalized Medicine at NorthShore University HealthSystem in Evanston, Ill. “Raising awareness with physicians and patients is critical, otherwise patients are getting an incomplete genetic assessment.”

This spring, a major association of medical geneticists issued new guidance for patients and doctors advising that women with PALB2 mutations be surveilled similarly to patients with BRCA mutations, and that, depending on family history, mastectomies could be an option to reduce the risk in some patients.

The guidance, issued by the American College of Medical Genetics and Genomics, called the PALB2 mutation the “third most important breast cancer gene after BRCA1 and BRCA2.” Guidelines from National Comprehensive Cancer Network, as well as from the medical genetics organization, suggest women with the PALB2 mutation should have breast M.R.I.s and mammograms, alternating every six months. The guidance was based on peer-reviewed evidence by a global team of experts in cancer genetics.

Dr. Hulick said the risk of developing breast cancer was 40 percent to 60 percent greater among women with the PALB2 mutation, similar to the risk from BRCA.

“The reality is we are all at risk for something, it’s just whether we have that line of sight. It’s a real awareness issue,” Dr. Hulick said. “Now people can put PALB2 in their care plan along with structured family history tools.


Susan Karnick of Crystal Lake, Ill., opted for a prophylactic mastectomy when she tested positive for the gene. After surgery, it was found she had stage one breast cancer in one breast and five precancerous lesions in the other, despite routine scans.Credit…Taylor Glascock for The New York Times

Susan Karnick’s mother had breast cancer years ago, and genetic testing showed no BRCA mutation. Ms. Karnick, 55, of Crystal Lake, Ill., had breast calcification and was alternating mammograms and M.R.I.s every six months when her doctor suggested genetic testing. It showed she had PALB2.

After consulting with a high-risk oncologist, she opted for a prophylactic mastectomy. After the surgery, pathology showed she had stage one breast cancer in one breast and five precancerous lesions in the other, in spite of the surveillance every six months.

“My doctor said he was happy I didn’t even wait a month or two,” Ms. Karnick said. “I needed no chemo or radiation.”

She is enrolled in a pancreatic cancer prevention program at the University of Wisconsin and will undergo screening. Because she had previously had a hysterectomy to treat benign ovarian cysts, ovarian cancer is not a concern.

“I was just so grateful for that genetic testing,” she said. “It was stressful and scary but my goodness, I had lifesaving surgery and I would not have known.”

Douglas R. Stewart, a co-author of the new guidance, said that PALB2 is sometimes referred to as “BRCA3, given its importance in risk of breast cancer.” He added that those with the mutation “face challenging questions, especially about their personal risk to develop cancers of the breast, ovaries and pancreas, and how to manage that risk.”

Everett Lally, a genetic counselor at Seattle Cancer Care Center said it is not only family history but there are psychological considerations as well. He said the women with a first degree relative with breast cancer will likely find it easier to decide on a bilateral mastectomy than a woman with PALB2 mutation and no history of breast cancer.

The BRCA mutation received wide publicity in 2013 when the actress Angelina Jolie underwent a prophylactic mastectomy upon learning she had it. Her mother had breast cancer and died at age 56 of ovarian cancer.

Historically, when genetic testing was more expensive, specific target testing was done. Today, Dr. Hulick said, testing is much cheaper, and for women with an indication of breast cancer, broad screening panels, which include PALB2 and other cancer genes, are often done. But he noted that genetic testing in general does not yet reach enough women.

Over the course of their lives, women have about a 12 percent chance of developing breast cancer and a 1.2 percent chance of developing ovarian cancer, according to the National Cancer Institute.

Unlike BRCA1 and BRCA2, which are often found in the Ashkenazi Jewish population, PALB2 is not associated with the Ashkenazi group. Some studies have found a PALB2 association with Finish and French Canadian and Greek women, but experts say more research is needed.

The new guidelines for the PALB2 mutation, particularly for those who have pancreatic cancer in their families, now suggest pancreatic screening, which involves having M.R.I.s of the pancreas as well as an endoscopic ultrasound. The new guidelines not only improve care, but a recent study in Journal of Gastrointestinal Surgery shows early detection improves outcomes, which encourages insurance to cover screening.


Ms. Marsh keeps a genealogy chart to track the mutation for Dr. Marc Tischkowitz, a geneticist at the University of Cambridge and creator of the PALB2 Interest Group, who is conducting a study on the mutation.Credit…Jovelle Tamayo for The New York Times

Heidi Marsh, 46, of Seattle, tested positive for the PALB2 mutation after her mother — a breast cancer and pancreatic cancer patient — was found to have it. She said her own doctor was unaware of the gene.

“My OB-GYN was aware of my mom’s history and never suggested genetic testing,” Ms. Marsh said. “She never heard of it. I educated her. The oncologist she sent me to did not suggest surgery.”

But Seattle Cancer Care Alliance, a partner of Fred Hutchinson Cancer Research Center, where Ms. Marsh’s mother had been an oncology nurse, did know about the gene mutation. The group immediately put together a team that included a surgical oncologist, a pancreatic cancer specialist, a geneticist, a nutritionist and a social worker.

“This has been life-changing,” said Ms. Marsh, who had her fallopian tubes removed in April. (She was told most ovarian cancer first occurs in the tubes. She plans to remove her ovaries after menopause.)

She will have breast monitoring with alternating mammograms and breast M.R.I.s every six months. She has already had an endoscopic ultrasound to look at her pancreas.

She has found a Facebook group, PALB2 Warriors, to be helpful. Because she has a background in health care — she was a phlebotomist — she says she looks further than individual postings, to studies that are placebo-controlled and peer-reviewed for information. But when it comes to personal stories of experience with prophylactic mastectomies and reconstruction, she says that is invaluable.

“This was not remotely on my radar screen,” she said. “In one sense I feel empowered. But I also feel like I am waiting for the other shoe to drop, that cancer will be inevitable.”

But mostly, she is thankful that she knows about PALB2 and the risks involved.

“It’s an alarm clock and a wake-up call,” she said. “You can do something about it if you choose.”