Breast Cancer, Ovarian Cancer, and the PALB2 Gene

A publication in today’s New England Journal of Medicine describes another important gene responsible for some hereditary breast and ovarian cancers. Dr. Antoniou and colleagues at Cambridge University found that mutations in the PALB2 gene were associated with a 9.5 times higher rate of breast cancer, and a 2.3 times higher rate of ovarian cancer in women. They also found an 8 times higher risk of male breast cancer.

A family history of breast cancer was also important in calculating risk. If there was no family history, the lifetime risk of breast cancer was 33%. With a family history, the lifetime risk was 58%. PALB2 carriers are estimated to be a cause of 0.6 – 3.9% of all breast cancers, depending on the country of origin.

This increased risk is similar in magnitude to the BRCA gene; BRCA carriers have a 45 – 56% lifetime risk of breast cancer, and an 11 – 39% lifetime risk of ovarian cancer. BRCA carriers account for 5 -10% of all breast cancer patients, and 15% of all ovarian cancer patients.

To put this in perspective, in the overall population, women have a lifetime risk of about 12% of developing breast cancer, and a 1.4% lifetime risk of developing ovarian cancer.

The significance of this study is that we have found many families who all have one of these cancers, and yet are not BRCA carriers. We have theorized that there must be another BRCA-type gene as yet undiscovered that would account for these families and their high rates of cancer. PALB2 appears to code for a protein that interacts with BRCA1, so it comes as no surprise that a PALB2 mutation could cause similar risks. I suspect we will continue to find more of these mutational risks in the years to come.

This is an uncommon cause of breast cancer, though clearly an important one. Who should be tested for this? Today, I would recommend testing only for families with high rates of breast and ovarian cancer who have tested negative for the BRCA gene. Read more here:

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