By Talia Golan, MD and Sue Friedman, DVM
BRCA and pancreatic cancer
The link between breast and ovarian cancer and BRCA mutations has been known since the 1990s. However, the awareness that these mutations also increase pancreatic cancer risk is more recent. If all patients with pancreatic cancer were tested for a BRCA1 or BRCA2 mutation, about 5% would test positive. That number is higher—about 10-15%—for people who are Ashkenazi Jewish, a population in whom BRCA mutations are quite prevalent.
People with inherited BRCA1 and BRCA2 mutations have an increased cancer risk; for pancreatic cancer, their estimated lifetime risk is about 5%. Because BRCA genes are involved in the repair of some types DNA damage in cells, BRCA-related cancers may be more sensitive to anti-cancer therapies that damage DNA, such as certain types of chemotherapy, radiation, and some targeted therapies, including PARP inhibitors. Studies show that both ovarian cancer and pancreatic cancer patients with inherited BRCA mutations may survive longer than those who do not have BRCA mutations.
BRCA and platinum sensitivity
A recent study showed that patients with stage 3 or 4 pancreatic cancer who had a BRCA mutation and were treated with platinum-containing chemotherapy had longer overall survival of 22 months, compared to 7 months for those who did not get a platinum-containing drug. These results suggest that knowing pancreatic cancer patients’ BRCA mutation status can predict how much they might benefit from the use of platinum-based chemotherapy.
BRCA and PARP inhibition
Poly (ADP-ribose)-polymerase (PARP) is an enzyme found in our bodies that is involved in repairing DNA damage. A new class of cancer treatments called “PARP inhibitors” focus on inhibiting the PARP enzyme. Cancers caused by BRCA mutations appear to be sensitive to PARP inhibitors. The PARP inhibitor olaparib (Lynparza) is approved by the Food and Drug Administration for treating ovarian cancer patients with BRCA1 or BRCA2 mutations who have completed 3 prior lines of chemotherapy. PARP inhibitors are being researched for treating other types of cancer, both alone and in combination with chemotherapy, immunotherapy, and radiation. Clinical trials testing PARP inhibitors in pancreatic cancer patients with inherited mutations in BRCA1 or BRCA2 are ongoing, and preliminary results are promising. A phase II study of olaparib BRCA–mutant cancers was recently reported; 23 patients with advanced pancreatic cancers were included, all of whom had previously received the drug gemcitabine. The overall response rate was 22% with a progression-free survival of 4.6 months and an overall survival of 9.8 months. These preliminary data suggest that pancreatic cancer patients with inherited BRCA mutations may benefit from PARP inhibitors.
These studies suggest that pancreatic cancers in people with BRCA1 and BRCA2 mutations are different from other pancreatic cancers, and require a different treatment approach. It is very important for patients with pancreatic cancer to learn if they have a BRCA mutation, so that they can receive platinum chemotherapy and have the opportunity to participate in appropriate clinical trials if they so choose. For example, the POLO Study is an important phase III clinical trial enrolling metastatic pancreatic cancer patients with BRCA mutations to determine whether adding the PARP inhibitor, olaparib after first line chemotherapy improves survival. Additionally, relatives of people with pancreatic cancer may benefit from genetic counseling and testing and may qualify for medical options to lower their risk for cancer.
Dr. Talia Golan is the Medical Director, Phase I Program at the Chaim Sheba Medical Centre of the Tel Aviv University. Dr. Golan is a clinician-scientist currently conducting translational laboratory research while also serving as the Medical Director. Her clinical interest is in patients with pancreatic cancer. Dr. Golan’s career goals include expertise in clinical medicine, translational laboratory research and drug development.
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Tags: brca, BRCA 1, BRCA 2, brca research, brca testing, BRCA1, clinical trials, gene testing, HBOC, hereditary cancer research, pancreatic cancer, personalized medicine