- Hereditary Breast and Ovarian Cancer syndrome (HBOC)
- Lynch syndrome/Hereditary Non-Polyposis Colorectal Cancer (HNPCC)
- Familial Adenomatous Polyposis (FAP)/Attenuated Familial Adenomatous Polyposis (AFAP)
- MUTYH-associated Polyposis syndrome (MAP)
- MUTYH-associated Colon Cancer Risk
- Melanoma Cancer Syndrome (MCS)
- Li-Fraumeni Syndrome (LFS)
- PTEN Hamartoma Tumor syndrome (PHTS)
- Peutz-Jeghers Syndrome
- Hereditary Diffuse Gastric Cancer (HDGC) Syndrome
- Juvenile Polyposis Syndrome (JPS)
- Juvenile Polyposis Syndrome (JPS) and Hereditary Hemorrhagic Telangiectasia (HHT)
- PALB2-associated Cancer Risk
- CHEK2-associated Cancer Risk
- ATM-associated Cancer Risk
- NBN-associated Cancer Risk
- BARD1-associated Cancer Risk
- BRIP1-associated Cancer Risk
- RAD51C-associated Cancer Risk
- RAD51D-associated Cancer Risk
- Polymerase Proofreading-associated Syndrome (PPAS)
- Hereditary Mixed Polyposis Syndrome (HMPS)
PALB2 ASSOCIATED CANCER RISKS
PALB2 ASSOCIATED CANCER RISKS
What does it mean to have a PALB2 gene mutation?
Women with mutations in the PALB2 gene have an increased risk for breast cancer, sometimes at relatively young ages. This increased risk is not as high as what is seen in women with mutations in the BRCA1 and BRCA2 genes. However, it is high enough to consider ways to reduce cancer risk and to increase screening in an attempt to find any breast cancers that may develop as early as possible.
Men with mutations in the PALB2 gene also have an increased risk for breast cancer. This risk is much smaller than the risk for women.
Men and women with PALB2 mutations have an increased risk for pancreatic cancer. The exact size of this risk is not known, but it is probably higher in families where there is a family history of one or more people who have had pancreatic cancer.
What can be done to protect people with PALB2 mutations from cancer?
Women with PALB2 mutations may benefit from a variety of options to reduce their risk for breast cancer. This could include starting screenings at younger ages than normal and having the screenings more often than typically recommended. If there is a family history of pancreatic cancer, it may be reasonable to also consider screening for pancreatic cancer, but this is considered experimental at this time.
We have only recently discovered that PALB2 mutations increase cancer risks. As we learn more, there may be new information about risks for other cancers and the best ways to reduce those risks. For this reason, people with PALB2 mutations may benefit from speaking with healthcare providers who specialize in the genetics of inherited cancer risks.
Associated Syndrome Name: PALB2-associated Cancer Risk
PALB2 Summary Cancer Risk Table
|Cancer||Genetic Cancer Risk|
|Female Breast||High Risk|
|Male Breast||Elevated Risk|
PALB2 gene Overview
PALB2-associated Cancer Risk 1, 2, 3, 4, 5, 6
- Women with PALB2 mutations have a risk for breast cancer that is significantly increased over the 12.5% lifetime risk for women in the general population of the United States. Estimates of this risk vary and are influenced by family history. The highest estimate of a 58% risk of breast cancer to age 70 applies to women who have 2 or more close relatives with breast cancer at age 50 or younger.
- PALB2 mutations have been found in families with 2 or more cases of pancreatic cancer in close relatives, indicating that there is an increased risk for pancreatic cancer in men and women with PALB2 mutations. The exact risk is unknown.
- PALB2 mutations have been found in families with cases of male breast cancer, indicating that there may be an increased risk for male breast cancer in some men with PALB2 mutations. The exact risk is unknown.
- Although there are increased risks for cancer in men and women with mutations in PALB2, there are interventions that may reduce these risks. Guidelines from the National Comprehensive Cancer Network (NCCN) that may apply are listed below. Since information about the cancer risks associated with PALB2 mutations is relatively new, and there is still some uncertainty about the best ways to reduce these risks, it may be appropriate to interpret these results in consultation with cancer genetics experts in this emerging area of knowledge.
PALB2 gene Cancer Risk Table
|Cancer Type||Age Range||Cancer Risk||Risk for General Population|
|Female Breast||To age 506, 7||14%||1.9%|
|To age 701, 2, 3, 6, 7||17-58%||7.1%|
|Pancreatic||To age 804, 5, 7||Elevated risk||1%|
|Male Breast||To age 801, 7||Elevated risk||0.1%|
PALB2 Cancer Risk Management Table
The overview of medical management options provided is a summary of professional society guidelines as of the last Myriad update shown on this page. The specific reference provided (e.g., NCCN guidelines) should be consulted for more details and up-to-date information before developing a treatment plan for a particular patient.
This overview is provided for informational purposes only and does not constitute a recommendation. While the medical society guidelines summarized herein provide important and useful information, medical management decisions for any particular patient should be made in consultation between that patient and his or her healthcare provider and may differ from society guidelines based on a complete understanding of the patient’s personal medical history, surgeries and other treatments.
|Cancer Type||Procedure||Age to Begin||Frequency |
(Unless otherwise indicated by findings)
|Female Breast||Breast awareness - Women should be familiar with their breasts and promptly report changes to their healthcare provider. Periodic, consistent breast self-examination (BSE) may facilitate breast awareness.8||Individualized||NA|
|Clinical encounter, including clinical breast exam, ongoing risk assessment and risk-reduction counseling8||When genetic risk is identified||Every 6 to 12 months|
|Mammography with consideration of tomosynthesis and breast MRI with contrast9||Age 30, or modified to a younger age based on family history||Annually|
|Consider additional risk-reduction strategies.8, 9||Individualized||NA|
|Pancreatic||For patients with a family history of pancreatic cancer, consider available options for pancreatic cancer screening, including the possibility of endoscopic ultrasonography (EUS) and MRI/magnetic resonance cholangiopancreatography (MRCP). It is recommended that patients who are candidates for pancreatic cancer screening be managed by a multidisciplinary team with experience in the screening for pancreatic cancer, preferably within research protocols.10, 13||Age 50, or 10 years younger than the earliest age of pancreatic cancer diagnosis in the family||Annually|
|Provide education about smoking cessation to reduce pancreatic cancer risk10||Individualized||Individualized|
|Male Breast||Currently there are no specific medical management guidelines for breast cancer risk in mutation carriers. However, the increase in risk warrants consideration of options for male breast cancer screening, such as patient breast awareness education and clinical breast examinations.8, 9||Individualized||NA|
|For Patients With A Cancer Diagnosis||For patients with a gene mutation and a diagnosis of cancer, targeted therapies may be available as a treatment option for certain tumor types (e.g., platinum chemotherapy, PARP-inhibitors)11, 12||NA||NA|
Information for Family Members
The following information for Family Members will appear as part of the MMT for a patient found to have a mutation in the PALB2 gene.
A major potential benefit of myRisk genetic testing for hereditary cancer risk is the opportunity to prevent cancer in relatives of patients in whom clinically significant mutations are identified. Healthcare providers have an important role in making sure that patients with clinically significant mutations are informed about the risks to relatives, and ways in which genetic testing can guide lifesaving interventions.
In rare instances, an individual may inherit mutations in both copies of the PALB2 gene, leading to the condition Fanconi Anemia, Complementation Group N (FANCN). This condition is extremely rare, but is thought to include physical abnormalities, growth retardation, progressive bone marrow failure and a high risk for cancer. The children of this patient are at risk of inheriting FANCN only if the other parent is also a carrier of a PALB2 mutation. It may be appropriate to screen the spouse/partner of this patient for PALB2 mutations.14
- Casadei S, et al. Contribution of inherited mutations in the BRCA2-interacting protein PALB2 to familial breast cancer. Cancer Res. 2011 71:2222-9. PMID: 21285249.
- Erkko H, et al. A recurrent mutation in PALB2 in Finnish cancer families. Nature. 2007 446:316-9. PMID: 17287723.
- Rahman N, et al. Breast Cancer Susceptibility Collaboration (UK). PALB2, which encodes a BRCA2-interacting protein, is a breast cancer susceptibility gene. Nat Genet. 2007 39:165-7. PMID: 17200668.
- Jones S, et al. Exomic sequencing identifies PALB2 as a pancreatic cancer susceptibility gene. Science. 2009 324:217. PMID: 19264984.
- Slater EP, et al. PALB2 mutations in European familial pancreatic cancer families. Clin Genet. 2010 78:490-4. PMID: 20412113
- Antoniou AC, et al. Breast-cancer risk in families with mutations in PALB2. N Engl J Med. 2014 371:497-506. PMID: 25099575.
- Fast Stats: An interactive tool for access to SEER cancer statistics. Surveillance Research Program, National Cancer Institute. https://seer.cancer.gov/faststats. (Accessed on 1-2-2017)
- Bevers TB, et al. NCCN Clinical Practice Guidelines in Oncology®: Breast Cancer Screening and Diagnosis. V 2.2018. May 18. Available at http://www.nccn.org.
- Daly M et al. NCCN Clinical Practice Guidelines in Oncology®: Genetic/Familial High-Risk Assessment: Breast and Ovarian. V 2.2019. July 30. Available at http://www.nccn.org.
- Syngal S, et al. ACG clinical guideline: Genetic testing and management of hereditary gastrointestinal cancer syndromes. Am J Gastroenterol. 2015 110:223-62. PMID: 25645574.
- Mohler JL, et al. NCCN Clinical Practice Guidelines in Oncology®: Prostate Cancer. V 4.2018. August 15. Available at http://www.nccn.org.
- Armstrong DK, et al. NCCN Clinical Practice Guidelines in Oncology®: Ovarian Cancer. V 2.2018. March 9. Available at http://www.nccn.org.
- Canto MI, et al. International Cancer of the Pancreas Screening (CAPS) Consortium summit on the management of patients with increased risk for familial pancreatic cancer. Gut. 2013 62:339-47. PMID: 23135763.
- Reid S, et al. Biallelic mutations in PALB2 cause Fanconi anemia subtype FA-N and predispose to childhood cancer. Nat Genet. 2007 39:162-4. PMID: 17200671.
Last Updated on 09-Jul-2019