BRCA1 and BRCA2 are far and away the most commonly inherited mutations that predispose women to breast and ovarian cancer. However, since the relatively recent use of panel testing, multiple genes have been discovered that can also predispose women to breast, ovarian, and other cancers. One of these genes is called PALB2 (commonly called pal…b…2). PALB2, interestingly, interacts with BRCA1 and BRCA2 to repair damaged DNA. Humans have 23 pairs of chromosomes. BRCA1 is located on chromosome 17; BRCA2 is on chromosome 13; and PALB2 is on chromosome 16.

For the most part, all of our genes come in pairs. For instance, we have two chromosome 17s. We have a BRCA1 on each of these chromosomes. We are therefore said to have two “copies” of BRCA1. In the case of PALB2, when both copies are mutated (genetic code is altered), it causes a disease called Fanconi’s anemia. This ailment predisposes people to childhood malignancies, including leukemia and bone marrow failure. When PALB2 mutations occur in only one chromosome, it predisposes women to breast and ovarian cancer. Depending on the population tested, PALB2 mutations are found in 1% to 4% of families with breast cancer who test negative for BRCA1 and BRCA2. It is, therefore, one of the rarer breast cancer susceptibility genes. Because of the low frequency of PALB2, there is a lack of data for the spectrum of breast cancer in patients who carry these genetic mutations. A new study from China has shed some light on this genetic mutation.

The researchers determined the genetic code of PALB2 genes in 21,216 unselected patients with primary breast cancer, along with 5,890 healthy Chinese women. They then assessed the odds of breast cancer associated with this mutation and explored clinical outcomes. Of the 16,501 patients that were BRCA negative yet had developed breast cancer, 160 were PALB2 mutation-positive (0.97%). This means that about 1% of women with breast cancer carry a mutant form of PALB2. In healthy controls without breast cancer, 11 of 5,890 had mutations (0.19%). The risk of breast cancer was approximately 5 times normal for patients carrying mutations in PALB2. In women less than 30 years old who carried an abnormal PALB2 gene, the risk was over 10 times normal with a range of 9 to 25 times normal!

Tumor Characteristics

For those patients with breast cancer who also tested positive for PALB2, a significantly higher number of them were 30 years old or younger at diagnosis compared to those older than 30. Patients with PALB2 mutations were significantly more likely to have triple-negative breast cancers than non-carriers, though this rate was not nearly as high it is as for carriers of BRCA mutations: 14% for PALB2, 25-30% for BRCA2, and 70% for BRCA1. Moreover, carriers are more likely than non-carriers to have bigger tumors that are greater than or equal to 2cm, positive axillary lymph nodes, bilateral breast cancers, as well as a family history of breast and ovarian cancer. Interestingly, carriers also had an increase in the incidence of family histories of other cancers, not including breast or ovarian cancer.

The authors concluded that because of the interaction of PALB2 with the BRCA genes, patients with breast cancer who also carry a mutant form of the PALB2 gene may be sensitive to biologic drugs called PARP inhibitors, which many are hopeful will increase the cure rate of this form of breast cancer.