Update: Genetic causes of hereditary pancreatic cancer: BRCA and beyond
|At a glance||Clinical trials|
|Genes associated with pancreatic cancer||Questions to ask your doctor|
|What does this mean for me?||Resources and references|
UPDATE AT A GLANCE
This update is about:
Inherited mutations in pancreatic cancer genes and the importance of identifying patients who have them.
Why is this update important?
Between 10–20 percent of all pancreatic cancer is thought to be due to an inherited mutation.
- About 3-10 percent of people with pancreatic cancer have a family history of the disease.
- Inherited mutations in and are the most common cause of familial pancreatic cancer. Together, about 6 percent of all pancreatic cancer patients have an inherited mutation in or .
- Almost 14 percent of people with pancreatic cancer have a mutation.
- Studies looking at patients who do not have a family history of pancreatic cancer have found that 4-11 percent have an inherited mutation in a gene associated with pancreatic cancer.
Genetic panel testing, which looks for mutations in many genes at one time rather than just 1 or 2 at a time, has become more widespread in recent years and has led to a better understanding of which genes contribute to hereditary pancreatic cancer. Genes that are generally included in panel testing include , , , CDKN2A, , , , , and .
Of these genes, panel testing has shown that:
- Mutations in are found in 2-3 percent of pancreatic cancer cases.
- Mutations in genes (, , , and ) are found in <1 percent of cases.
- Mutations in other genes (CDKN2A, , and ) are found in fewer than < 1 percent of cases.
One study found that 17 percent of patients with a family history of pancreatic cancer who had panel testing had an inherited mutation, suggesting the importance of family history. Being diagnosed at a younger age was also associated with an increased likelihood of having a mutation.
Genes associated with hereditary pancreatic cancer and risk
The lifetime risk for pancreatic cancer in the general population is 1.6 percent. The general population includes people with and without mutations. People with the following mutations had an increased risk for pancreatic cancer compared to people without a mutation.
|Gene||Increase in Pancreatic Cancer Risk Compared to
Someone Without the Mutation
|Other Associated Cancers|
|2-4 times||Breast, ovarian,|
|3-8 times||Breast, ovarian, , melanoma|
|, , , ,
|Up to 9 times||Colorectal, endometrial (uterine), ovarian,|
|()||132 times||Breast, gastrointestinal, gynecological|
Source: Robert Pilarski, MS, LGC, MSW, LSW, ASCO June 2019
In addition to mutations in and , numerous other inherited mutations increase the risk of pancreatic and other cancers. The National Comprehensive Cancer Network (NCCN) now recommends that all pancreatic cancer patients be offered genetic testing and counseling to determine whether they have inherited a . Those who test positive for an inherited mutation may be eligible for different treatment options, such as PARP inhibitors or immunotherapies, and they may require screening for additional cancers. They may also need to alert their family members to the increased risks of certain cancers. Finally, the identification of mutations may make a patient eligible for specific clinical trials that are looking at targeted therapies for carriers of particular mutations.
What does this mean for me?
If you have been diagnosed with pancreatic cancer, you should speak with your health care provider about receiving genetic counseling and testing to determine if you might carry an inherited mutation in a gene that is associated with hereditary pancreatic cancer. The results may be important for your treatment (including enrollment in clinical trials) and for your family.
If you have a family history of pancreatic cancer, you should speak with a health care provider about referral for genetic counseling and testing.
If you do not have pancreatic cancer but you know that you carry an inherited mutation in a relevant gene (see the table in this article) and you meet the screening guidelines outlined here, you should speak to your health care provider about receiving annual screening for pancreatic cancer.
Inherited mutations in a number of genes are associated with increase pancreatic cancer risk. It is important that people with pancreatic cancer are offered genetic testing and counseling to determine if they carry a in one of these genes, as the results can impact treatment decisions, screening and risk management for other cancers, and family members’ risk. It is also important that people without pancreatic cancer but with an inherited mutation in a known pancreatic cancer risk gene are aware of screening guidelines and receive screening as appropriate.
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This article is relevant for:
People diagnosed with pancreatic cancer
This article is also relevant for:
People with a genetic mutation linked to cancer risk
Pancreatic cancer survivors
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National Comprehensive Cancer Network (NCCN) Guidelines
The NCCN recommends the following screening for people at increased risk for pancreatic cancer:
- Discuss the benefits and risks of screening with their doctor. Screening should be performed by a facility that is experienced with screening for pancreatic cancer. The recommended age for considering screening depends on a person’s family history of pancreatic cancer and varies by type of gene mutation.
- Consider screening with magnetic resonance cholangiopancreatography (MRCP) and/or endoscopic (EUS)
- Consider participating in a pancreatic cancer screening study
NCCN recommends that people with inherited mutations in the following genes (with or without a family history of cancer) "consider pancreatic cancer screening" with MRCP or EUS:
- : (): Consider pancreatic cancer screening by MRCP or EUS every 1-2 years beginning at age 30-35 or 10 years younger than the earliest pancreatic cancer in the family.
- CDKN2A: Consider pancreatic cancer screening beginning at age 40 or 10 years earlier than the earliest pancreatic cancer diagnosis in the family.
NCCN guidelines recommend that people with an inherited mutation in one of the following genes and a family history of cancer "consider pancreatic cancer screening" with MRCP or EUS beginning at age 50 or 10 years earlier than the earliest pancreatic cancer diagnosis in the family: , , , , , , , , .
NCCN does not currently recommend pancreatic cancer screening for people with the above mutations who do not have a family history of cancer.
American Society for Gastrointestinal Endoscopy (ASGE) Guidelines
In February 2022, the ASGE released updated guidelines on pancreatic cancer screening for people with a or mutation. These guidelines recommended:
- All patients with a mutation regardless of family history of pancreatic cancer, should undergo annual screening for pancreatic cancer with MRI/MRCP or EUS beginning at age 50 (or 10 years earlier than the earliest pancreatic cancer in the family).
The National Comprehensive Cancer Network has guidelines on who should undergo genetic counseling and testing. The NCCN recommends genetic counseling and testing for anyone diagnosed with pancreatic cancer, using a comprehensive gene panel for .
- Should I have genetic testing for an inherited mutation?
- I had genetic testing in the past, should I have additional testing?
- Should I have pancreatic cancer screening?
- Will my insurance pay for pancreatic cancer screening?
The following are studies looking at risk management for pancreatic cancer:
- NCT03250078: A Pancreatic Cancer Screening Study in Hereditary High-Risk Individuals. The main goal of this study is to screen and detect pancreatic cancer and precursor lesions in individuals with a strong family history or genetic predisposition to pancreatic cancer. Magnetic Resonance Imaging and Magnetic cholangiopancreatography (MRI/MRCP) will be utilized to screen for pancreatic cancer or precursor lesions.
- NCT02478892: Preliminary Evaluation of Screening for Pancreatic Cancer in Patients With Inherited Genetic Risk. The study is a , observational study evaluating the utility of endoscopic or for the identification of preneoplastic and neoplastic pancreatic lesions in patients at high risk for pancreatic cancer, specifically those with BRCA1/2, or mutations.
- NCT03568630: Blood Markers of Early Pancreas Cancer. Identifying biomarkers of early pancreatic ductal () could facilitate screening for individuals at higher-than-average risk, expedite the diagnosis in individuals with symptoms and substantially improve an individual's chance of surviving the disease.
- NCT02206360: Pancreatic Cancer Early Detection Program (PCEDP). This is a study looking at esophageal as a screening for pancreatic cancer in high risk individuals.
- NCT03250078: A Pancreatic Cancer Screening Study in Hereditary High Risk Individuals. The goal is to screen for pancreatic cancer in individuals with a strong family history or genetic risk using Magnetic Resonance Imaging and Magnetic cholangiopancreatography (MRI/MRCP).
A number of other clinical trials for pancreatic cancer screening and prevention may be found here.
The following are studies enrolling people diagnosed with pancreatic cancer:
- NCT04548752: Adding Pembrolizumab to Olaparib to Treat Pancreatic Cancer in People with an Inherited Mutation. This study is researching whether adding the drug Pembrolizumab (Keytruda) to the Olaparib (Lynparza) works better than olaparib alone for treating pancreatic cancer in people with an inherited or mutation.
- NCT05252390: NUV-868 Alone and in Combination With PARP Inhibitors in Patients With Advanced .
This study will test how safe and effective the experimental drug NUV-868 is by itself and in combination with a in people with advanced .
- NCT04229004: Precision Promise Platform Trial for Pancreatic Cancer. This study tests different treatments for pancreatic cancer.
- NCT04267939: ATR Inhibitor BAY 1895344 Plus Phase 1b Study in Advanced and Ovarian Cancer. This study will look at how well advanced respond to treatment with the BAY1895344 combined with the niraparib.
- NCT04493060: Treating Pancreatic Cancer with an Inherited or Tumor BRCA1/2 or Mutation with and Dostarlimab. This study looks at how well the and the drug dostarlimab work together in treating patients with pancreatic cancer, who have an inherited or tumor mutation in , , , , , or .
- NCT03337087: Treating Pancreatic, Colorectal, Gastroesophageal, or Biliary Cancer with Chemotherapy and This study will look at how the works with chemotherapy to treat people with pancreatic, colorectal, gastroesophageal or biliary cancer. The study will measure the best dose and look at the side effects of this combination of drugs.
- NCT04150042: SHARON: A Clinical Trial for Cancer With an Inherited or Mutation Using Chemotherapy and Patients’ Own Stem Cells. The purpose of this study is to see whether the combination of melphalan, BCNU, vitamin B12b, and vitamin C, followed by autologous (self) bone marrow stem cell infusion, is safe and effective for treating patients with advanced pancreatic cancer or 4, breast cancer who have a , or inherited mutation.
- NCT04666740: Pembrolizumab and Olaparib for Pancreatic Cancer with or Exceptional Response to Platinum Chemotherapy. This is a study for people diagnosed with pancreatic cancer with a tumor test result called HRD-positive, or whose disease has responded well to first-line or second-line platinum therapy. The study will look at whether combining the drug pembrolizumab and the olaparib is a more effective treatment for this cancer than olaparib alone.
- NCT04858334: Olaparib or in Patients with Surgically Removed Pancreatic Cancer who have a , or Mutation (APOLLO). The purpose of EA2192 / APOLLO is to compare the usual approach (observation) to treatment for one year with olaparib, in patients with a , or mutation.
- NCT04657068: Treatment with ATR Inhibitor for Advanced or Solid Tumors. This study will look at how well a new oral known as an ATR inhibitor works on advanced or solid tumors with mutations in genes linked to damage repair. The study will look at the response to treatment with the drug ART0380 in combination with the chemotherapy agent, gemcitabine.
- NCT04550494: Treating Solid Tumors with an Inherited or Acquired Gene Mutation Using the Talazoparib. This study is looking whether the drug (also known as ) is safe and effective for treating people with advanced breast, gastric, ovarian, pancreatic, or other with an inherited mutation or an acquired mutation in certain repair genes, such as , , , , and others.
Other clinical trials for people with pancreatic cancer can be found here.
The following studies are looking at treatment for people with advanced .
- NCT05252390: NUV-868 Alone and in Combination With PARP Inhibitors in Patients With Advanced .This study will test the safety and effectiveness of the experimental drug NUV-868 alone and combined with a in people with advanced . This study is open to people whose cancer stopped responding or progressed on PARP inhibitors.
- NCT05169437: () in patients with inherited or tumor mutations in advanced (PAVO). PAVO is a Phase II study investigating if the niraparib is safe and effective for people with an advanced solid tumor who have an inherited gene mutation or a tumor with a mutation.
- NCT02264678: Ascending Doses of Ceralasertib in Combination With Chemotherapy and/or Novel Anti Cancer Agents. This is a study of ceralasertib administered orally in combination with chemotherapy regimens and/or novel anticancer agents to patients with advanced cancer. The study is enrolling people with inherited mutations, including , , , , , and people with tumors that are HRD-positive.
- NCT04644068: Study of AZD5305 as Monotherapy and in Combination With Anti-cancer Agents in Patients With Advanced Solid Malignancies (PETRA). This research is designed to learn whether treatment with a new , AZD5305, used alone or in combination with anti-cancer agents is safe, tolerable and has anti-cancer activity in patients with advanced . The study is open to people who have previously been treated with PARP inhibitors.
- NCT04267939: ATR Inhibitor Plus Study in Advanced and Ovarian Cancer. This study will look at how well people with advanced respond to treatment with the BAY1895344 in combination with the . This study is open to people with inherited mutations in , , and other genes. Contact the study coordinator for information about eligibility for people with mutations in other genes.
- NCT04657068: Treatment with ATR Inhibitor for Advanced or Solid Tumors. This study will look at how well a new oral known as an ATR inhibitor works on advanced or with mutations in genes that are linked to damage repair. This study is open to people who have an inherited or acquired or mutation or whose tumors are HRD-positive. This study is open to people whose cancer stopped responding or progressed on PARP inhibitors.
The following organizations offer peer support services for people with or at high risk for pancreatic cancer:
- FORCE peer support
- Our Message Boards allow people to connect with others who share their situation. Once registered, you can post on the Diagnosed With Cancer board to connect with other people who have been diagnosed.
- Peer Navigation Program will match you with a volunteer who shares your mutation and situation.
- Private Facebook Group
- Virtual and in-person support meetings
- Join a Zoom community group meeting.
- American Sign Language
- People of Color
- Let's Win PC
- The Healing NET Foundation is a nonprofit organization for people with neuroendocrine cancers.
- The Neuroendocrine Cancer Awareness Network (NCAN) is a non-profit organization dedicated to raising awareness of neuroendocrine cancer and providing support for caregivers and people with NETs.