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PALB2 gene
Associated Syndrome Name: PALB2-associated Cancer Risk
PALB2 Summary Cancer Risk Table
CANCER
GENETIC CANCER
RISK
Female Breast High Risk
Male Breast
Elevated Risk
Pancreatic
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
Female Breast
AGE RANGE
To age 50
To age 70
Pancreatic
To age 80
Male Breast
To age 80
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1, 2, 3, 6
4, 5
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PALB2 Cancer Risk Management Table
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CANCER RISK
RISK FOR GENERAL
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POPULATION
14%
1.9%
17-58%
7.3%
Elevated risk
1%
Elevated risk
0.1%
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
Female
Breast
PROCEDURE
AGE TO BEGIN
Breast awareness - Women should be familiar with their
breasts and promptly report changes to their healthcare
provider. Periodic, consistent breast self-examination (BSE)
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may facilitate breast awareness.
Individualized
NA
Clinical encounter, including clinical breast exam, ongoing risk
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assessment and risk reduction counseling
When genetic risk
is identified
Every 6 to
12 months
Age 30, or
modified to a
younger age
based on family
history
Annually
Individualized
NA
Consider additional risk-reduction strategies.
Individualized
NA
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
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pancreatic cancer, preferably within research protocols.
Individualized
NA
Individualized
NA
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Mammography and consideration of breast MRI with contrast
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Consider risk-reducing mastectomy.
8, 9
Pancreatic
FREQUENCY
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, clinical breast examinations, and mammography,
8, 9
particularly for men with gynecomastia.
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
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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
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appropriate to screen the spouse/partner of this patient for PALB2 mutations.
References
1. 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.
2. Erkko H, et al. A recurrent mutation in PALB2 in Finnish cancer families. Nature. 2007 446:316-9. PMID:
17287723.
3. 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.
4. Jones S, et al. Exomic sequencing identifies PALB2 as a pancreatic cancer susceptibility gene. Science. 2009
324:217. PMID: 19264984.
5. Slater EP, et al. PALB2 mutations in European familial pancreatic cancer families. Clin Genet. 2010 78:490-4.
PMID: 20412113
6. Antoniou AC, et al. Breast-cancer risk in families with mutations in PALB2. N Engl J Med. 2014 371:497-506.
PMID: 25099575.
7. Surveillance Research Program, National Cancer Institute SEER*Stat software (seer.cancer.gov/seerstat) V
8.0.1, Nov 19, 2012.
8. Daly M et al. NCCN Clinical Practice Guidelines in Oncology®: Genetic/Familial High-Risk Assessment: Breast
and Ovarian. V 1.2017. September 19. Available at http://www.nccn.org.
9. Bevers TB, et al. NCCN Clinical Practice Guidelines in Oncology®: Breast Cancer Screening and Diagnosis. V
1.2016. July 27. Available at http://www.nccn.org.
10. 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.
11. 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 01-Jun-2017
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