PALB2: What You Need to Know About This New Breast Cancer Gene
It’s many a young woman’s worst nightmare: At 39 years old, with two kids, a great job, and a promising future, you find a lump in your breast. So you call your mother, who had breast cancer, and you say, “Mom, I haven’t even scheduled my first mammogram — how can I already have a lump?”
You do a little online research and find out that National Cancer Institute’s published data puts the risk of developing breast cancer earlier than age 40 at less than 2 percent. For certain women with genetic predispositions, however, like those who test positive for a BRCA gene mutation, the risk is much higher.
Your mother talks you off the ledge and into the office of your doctor, who works you up and says, yes, indeed, you have breast cancer. Then your doctor suggests that you have the BRCA test. “It will help you decide treatment options,” she states calmly as she writes the order for the blood test. A few long days later, the test comes back negative. Great news! You don’t have to worry about breast cancer in the other breast, and you don’t have to have bilateral mastectomies, right?
Well, not necessarily. As I have been “soap boxing” for a while, BRCA negative does not mean “it does not run in the family.”
BRCA mutations for which cancer patients are routinely tested are not the only type of genetically transmitted cancers. Some researchers estimate that the BRCA mutations represent less than half of the genetically transmitted mutations. The other approximately 50 percent have only begun to be identified. Last week’s New England Journal of Medicine reports findings of the recently studied PALB2 mutation. PALB2 stands for Partner and Localizer of BRCA2, and is a gene that makes a protein that interacts with the BRCA 1 and 2 gene products. A mutation in a PALB2 gene has now been found to increase the breast cancer risk of a woman 40 or younger by eight or nine times compared to the general population.
The researchers looked at families with the PALB2 mutation and recorded the incidence of breast and ovarian cancer. The absolute risk for females with the PALB2 mutation by age 70 was estimated at 35 to 58 percent depending on how many female relatives had been previously diagnosed and the age of those relatives at diagnosis. The risk can be influenced by other genes that interact with the PALB2 gene and other familial factors, so it is not a definitive number at this time.
The PALB2 mutations are considered to account for less than 3 percent of the familial aggregations of breast cancer. The BRCA 1 and 2 genes account for another 50 percent, so we are slowly learning which genes to test for when a patient presents with breast cancer and a significant family history. It does not, however, give us a clear decision tree for women with significant family histories who test negative for all of these known genes. It’s the reason why we suggest discussions with genetic counselors and careful surveillance of these women.
There is still more research to do, more genes to identify, and more questions to be answered before we can identify which mutations put women at greatest risk and then what to do with this information. Until then, careful surveillance, developing good relationships with your physicians, and attention to family history all continue to be important for all women.
And don’t forget to do a monthly self-exam: The National Breast Cancer Foundationestimates that 40 percent of breast cancer is diagnosed because a woman finds a lump.
Elizabeth Chabner Thompson, MD, MPH, is a radiation oncologist and founder of BFFL Co (Best Friends for Life), a maker of recovery kits, surgical and recovery bras, and other products for patients undergoing mastectomy and other surgeries or treatments for cancer and other conditions.