Mutations in BRCA1 and BRCA2, most commonly linked with breast and ovarian cancers, are now gaining wider recognition for being associated with pancreatic cancer as well.
Individuals with BRCA1/2 mutations face a 5% risk of getting pancreatic cancer in their lifetime. An estimated 5% of patients with pancreatic cancer are BRCA carriers, and this subset of individuals may be more responsive to therapies that damage DNA, such as some chemotherapy, radiation therapy, and some targeted therapies. As a result, BRCA carriers with pancreatic cancer may live longer than their counterparts who do not carry the mutation.
“Currently, having pancreatic cancer is not necessarily enough medical history to trigger genetic counseling and testing,” explained Sue Friedman, DVM, executive director of Facing Our Risk of Cancer Empowered (FORCE).
“However, given that the cost for the test itself has gone down, there are studies open to people with pancreatic cancer. Given that people with pancreatic cancer and the mutations might qualify and may be indicated for platinum therapy, I think there are reasons for people to speak to their healthcare providers about genetic counseling and testing.”
Patients with pancreatic cancer and a BRCA mutation may benefit particularly from platinum-based chemotherapy. One recent study showed that patients with stage III or IV disease who received platinum chemotherapy lived 22 months, compared with 7 months for those who received non-platinum chemotherapies.
“In ovarian cancer, platinum therapy is considered standard of care, so someone diagnosed with a case of ovarian cancer is going to receive platinum,” Friedman said. “We also know that people with BRCA mutations tend to have a longer and better prognosis with ovarian cancer than people without. That may be due to the fact that platinum is particularly effective in people with mutations. There is current treatment available [for people with BRCA mutations] that is used after chemotherapy that may be beneficial for someone with pancreatic cancer. That might be a reason to know [if you have the mutation] because that might affect your treatment.”
Further, PARP inhibitors, such as the FDA-approved olaparib have shown significant activity in ovarian cancer, and many studies continue to look at this class of drugs in other types of cancer, both alone and in conjunction with chemotherapy, immunotherapy, and radiation.
A study of 23 patients with advanced pancreatic cancer demonstrated some promise for olaparib. In that trial, 22% of patients responded, median progression-free survival was 4.6 months, and overall survival was 9.8 months. The POLO trial is investigating the efficacy of olaparib in BRCA carriers with metastatic pancreatic cancer.
Outside of treatment, Friedman said, the need to detect pancreatic cancer earlier remains.
“There are some clinical trials right now that are looking at detection methods for pancreatic cancer,” Friedman said. “Someone with a BRCA mutation and a family history of pancreatic cancer should especially speak to their healthcare provider about the potential for detection. There are no real proven screenings that are considered outstanding, sensitive, and specific, but there are some institutions that will do things like the esophageal ultrasound to try and image the pancreas.”
“The problem with pancreatic cancer screening is the risk for a false positive. There are a number of trials that are trying to develop early detection, and we encourage people to participate in clinical trials whenever possible.”
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