Update: Genetic causes of hereditary pancreatic cancer: BRCA and beyond
An update on hereditary pancreatic cancer presented at the annual American Society of Clinical Oncology meeting covered genes and lifetime risk. The update emphasized that all pancreatic cancer patients should be offered genetic counseling and testing. Genetic test results may impact treatment, screening for other cancers and risk to family members. (11/26/19)
Most relevant for: People diagnosed with pancreatic cancer.
It may also be relevant for:
- people with a genetic mutation linked to cancer risk
- people newly diagnosed with cancer
- people with pancreatic cancer
Relevance: High
Research Timeline: Post Approval
Contents
| At a glance | Clinical trials |
| Beyond | Guidelines |
| 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 .
- 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 BRCA2 or BRCA1.
- Almost 14 percent of people with pancreatic cancer have a BRCA 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.
Beyond BRCA
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 BRCA1, BRCA2, , , , , , , and .
Of these genes, panel testing has shown that:
- Mutations in ATM are found in 2-3 percent of pancreatic cancer cases.
- Mutations in genes (MLH1, MSH2, MSH6, and PMS2) are found in <1 percent of cases.
- Mutations in other genes (CDKN2A, PALB2, and STK11) 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 |
|---|---|---|
| ATM | Unclear | Breast |
| BRCA1 | 2-4 times | Breast, ovarian, |
| BRCA2 | 3-8 times | Breast, ovarian, prostate, melanoma |
| CDKN2A | 13-22 times | Melanoma |
| MLH1, MSH2, MSH6, PMS2, (Lynch Syndrome) |
Up to 9 times | Colorectal, endometrial (uterine), ovarian, prostate |
| PALB2 | Unclear | Breast |
| STK11 () | 132 times | Breast, gastrointestinal, gynecological |
Source: Robert Pilarski, MS, LGC, MSW, LSW, ASCO June 2019
Summary:
In addition to mutations in BRCA1 and BRCA2, 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.
Conclusions:
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 germline mutation 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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Expert Guidelines
National Comprehensive Cancer Network (NCCN) Guidelines
The NCCN recommends the following 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 pancreatic cancer screening. 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.
The 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:
- STK11 (Peutz-Jeghers syndrome): Consider pancreatic cancer screening every 1-2 years, beginning at ages 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.
- ATM and BRCA2: Consider pancreatic cancer screening beginning at age 50 or 10 years earlier than the youngest case of pancreatic cancer in the family.
NCCN guidelines recommend that people with an inherited mutation in BRCA1, MLH1, MSH2, MSH6, EPCAM, PALB2, or 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.
The 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 BRCA1 or BRCA2 mutation. These guidelines recommended:
- All patients with a BRCA mutation, regardless of a 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.
Updated: 10/23/2024
Expert Guidelines
National Comprehensive Cancer Network guidelines reccomend genetic counseling and testing for anyone diagnosed with pancreatic cancer, using a comprehensive gene panel for .
Updated: 12/04/2021
Questions To Ask Your Doctor
- 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?
Open Clinical Trials
The following studies are looking at risk management for pancreatic cancer:
- NCT04970056: Pancreatic Cancer Early Detection for People at High Risk (PRECEDE). The study will collect clinical information, family history and samples (blood, saliva or cheek swab) from people and families at risk for pancreatic cancer.
- NCT02000089: Pancreatic Cancer Screening Study (CAPS5). The CAPS5 study is looking at screening for early cancer in people with an elevated lifetime risk of developing pancreatic cancer who are undergoing screening with endoscopic ultrasound, MRCP or .
- 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.
- NCT03568630: Blood Markers of Early Pancreas Cancer. This study looks at whether identifying biomarkers of early pancreatic ductal () could facilitate screening for individuals with higher-than-average risk, expedite the diagnosis in individuals with symptoms and substantially improve an individual's chance of surviving the disease.
- NCT03250078: A Pancreatic Cancer Screening Study in Hereditary High-Risk Individuals. The goal of this study is to use Magnetic Resonance Imaging and Magnetic Cholangiopancreatography (MRI/MRCP) to screen for pancreatic cancer in individuals with a strong family history or genetic risk .
Other clinical trials for pancreatic cancer screening and prevention may be found here.
Updated: 12/23/2024
Open Clinical Trials
The following treatment studies are enrolling people diagnosed with pancreatic cancer.
- NCT06545942: Treating Advanced Cancers with DNA-Repair Mutations Using MOMA-313 Alone or In Combination with the Olaparib. This trial studies an investigational drug called MOMA-313 given alone or together with the PARP inhibitor olaparib for people with advanced cancers, including pancreatic cancer with certain mutations.
- NCT04548752: Adding Pembrolizumab to to Treat Pancreatic Cancer in People with an Inherited BRCA Mutation. This study researches whether adding the drug pembrolizumab to the PARP inhibitor olaparib works better than olaparib alone for treating pancreatic cancer in people with an inherited BRCA1 or BRCA2 mutation.
- NCT06115499: Treating Metastatic BRCA1, BRCA2 or PALB2 Pancreatic Cancer Using a New Combination of Chemotherapy Drugs. This study will compare a 3-drug chemotherapy combination (NABPLAGEM; gemcitabine, cisplatin, nab-paclitaxel) to a 2-drug chemotherapy combination (gemcitabine/nab-paclitaxel) to treat people with pancreatic cancer with a BRCA1, BRCA2 or PALB2 mutation who have pancreatic cancer that has progressed after chemotherapy.
- NCT04858334: Olaparib or in Patients with Surgically Removed Pancreatic Cancer who have a BRCA1, BRCA2 or PALB2 Mutation (APOLLO). This study compares the usual approach (observation) to treatment for one year with olaparib in patients with a BRCA1, BRCA2 or PALB2 mutation.
- NCT04550494: Treating Metastatic Solid Tumors with an Inherited or Acquired Gene Mutation Using the PARP Inhibitor Talazoparib. This study looks at the safety and effectivenss of the drug for treating people with advanced breast, gastric, ovarian, pancreatic or other cancers with an inherited mutation or an acquired mutation in certain repair genes, such as BRCA1, BRCA2, ATM, , PALB2 and others.
- NCT05932862: Study of a New InvestigationaI Inhibitor to Treat People with Advanced . The study will test if an investigational treatment, XL309, is safe and works when used alone or in combination with a PARP inhibitor to treat people with advanced cancers, including pancreatic cancer.
- NCT04150042: SHARON: A Clinical Trial for Metastatic Cancer With an Inherited BRCA or PALB2 Mutation Using Chemotherapy and Patients’ Own Stem Cells. This study looks at whether 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 for people with a BRCA1, BRCA2 or PALB2 inherited mutation.
Other clinical trials for people with pancreatic cancer can be found here.
Updated: 05/24/2025
Open Clinical Trials
The following studies look at treatment for people with advanced solid tumors.
- NCT02264678: Ascending Doses of Ceralasertib in Combination With Chemotherapy and/or Novel Anti Cancer Agents. This is a study of orally administered ceralasertib combined with chemotherapy regimens and/or novel anticancer agents for patients with advanced cancer. The study enrolls people with tumors that are HRD-positive or who have inherited mutations in BRCA1, BRCA2, ATM, or .
- 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 PARP inhibitor, AZD5305, used alone or in combination with anti-cancer agents is safe, tolerable and has anti-cancer activity in patients with advanced solid tumors. The study is open to people who have previously been treated with PARP inhibitors.
- NCT04267939: ATR Inhibitor Plus Study in Advanced Solid Tumors and Ovarian Cancer. This study looks at how well people with advanced solid tumors respond to treatment with the BAY1895344 in combination with the PARP inhibitor niraparib. This study is open to people with inherited mutations in ATM, BRCA1, BRCA2 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 Metastatic Solid Tumors. This study looks at how well a new oral targeted therapy known as an ATR inhibitor works on advanced or metastatic solid tumors with mutations in genes that are linked to DNA damage repair. This study is open to people who have an inherited or acquired BRCA or ATM mutation or whose tumors are HRD-positive. This study is open to people whose cancer stopped responding or progressed on PARP inhibitors.
Updated: 03/28/2025
Peer Support
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.
- LGBTQIA
- Men
- American Sign Language
- People of Color
- Spanish-speakers
- PanCAN
- 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.
Updated: 08/23/2022
Related Resources
The following resources may be helpful for people with pancreatic cancer.
- FORCE resources:
- The following resources from other organizations are for people who have been diagnosed with pancreatic cancer:
- Let's Win PC is a nonprofit organization that enables doctors, scientists and patients to share fast-breaking information on potentially life-saving pancreatic cancer treatments and clinical trials.
- 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.
Updated: 09/18/2024