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PTEN gene
Associated Syndrome Name: PTEN Hamartoma Tumor syndrome
(PHTS)
PTEN Summary Cancer Risk Table
CANCER
GENETIC CANCER
RISK
Female Breast High Risk
Colorectal
High Risk
Endometrial
High Risk
Melanoma
High Risk
Other
High Risk
PTEN gene Overview
PTEN Hamartoma Tumor syndrome (PHTS)
1, 2, 3, 4
Individuals with PTEN mutations have PTEN Hamartoma Tumor Syndrome (PHTS).
Women with PHTS 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. Individuals with PHTS also have a significantly
increased risk for colorectal, endometrial, thyroid, renal and melanoma cancers. These cancers are often
diagnosed at relatively young ages.
A recent study has demonstrated that patients have a high risk for developing a second primary PHTSassociated cancer following their first diagnosis, and the risk may be particularly high for a second primary
breast cancer.
Patients with PHTS often have a wide variety of other, non-malignant features of the condition, some of
which may require medical attention. Examples are macrocephaly, colorectal polyps of various types,
Lhermitte-Duclos disease (a hamartomatous brain tumor), and distinctive skin findings such as
trichilemmomas, acral keratoses and papillomatous papules. Developmental delay and/or autism spectrum
disorders may also be present.
A subset of patients with PHTS may have a diagnosis of other syndromes, such as Cowden Syndrome (CS),
Bannayan-Riley-Ruvalcaba Syndrome (BRRS), PTEN-related Proteus Syndrome or Proteus-like Syndrome,
based on other clinical features. Some of these conditions have features that may require intervention in
infancy or childhood.
Although there are high risks for cancer in patients with PHTS, these risks can be reduced with appropriate
medical management. Guidelines from the National Comprehensive Cancer Network (NCCN) are listed
below. Management of patients with PHTS poses challenges due to the complexity of the condition and it is
recommended that patients with PTEN mutations and a diagnosis of PHTS be managed by a
multidisciplinary team with expertise in medical genetics and the care of patients with hereditary cancer
syndromes.
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PTEN gene Cancer Risk Table
CANCER TYPE
AGE RANGE
Overall cancer risk (male
and female)
To age 70
Female Breast
To age 70
Endometrial
To age 70
Thyroid
To age 70
Colorectal
To age 70
Renal
To age 70
Melanoma
To age 70
Other - Non-malignant
features of PHTS
All ages
6, 7
1, 6, 7, 8
1, 6, 8
1, 6, 7, 8
1, 6, 8
1, 6, 8
1, 7, 8
1, 2, 3
CANCER RISK
RISK FOR GENERAL
POPULATION
85%-89%
20.9%
77%-85%
7.3%
19%-28%
1.6%
21%-38%
0.8%
9%-16%
1.9%
15%-34%
0.8%
Up to 6%
1.1%
As described in the
Overview above, PHTS is
associated with nonmalignant clinical
features, some of which
may require medical
intervention as early as
infancy.
NA
PTEN 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
Overall cancer
risk
2
PROCEDURE
Comprehensive physical examination and
general education about the signs and
symptoms of cancer, with particular
1
attention to thyroid cancer.
AGE TO BEGIN
18 years or 5 years before the
youngest age of a PHTSrelated cancer in family
FREQUENCY
Annually
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
1
(BSE) may facilitate breast awareness.
18 years
NA
Clinical breast examination
25 years, or 5 to 10 years
younger than the earliest
diagnosis in the family,
whichever comes first.
Every 6 to
12 months
Mammography and breast MRI with contrast
30 to 35 years, or 5 to 10
years younger than the
earliest diagnosis in the
family, whichever comes first
Annually
Consider risk-reducing mastectomy.
Individualized
NA
Patient education about endometrial cancer
1
symptoms.
Individualized
NA
Consider endometrial sampling and
1
transvaginal ultrasound.
30 to 35 years
Annually
After completion of
childbearing
NA
At time of PHTS diagnosis
Annually
35 years, or 5 to 10 years
younger than the earliest
diagnosis in the family if a
family member was diagnosed
under age 40
Every 5
years
40 years
Every 1 to 2
years
1
1
1
Endometrial
Consider hysterectomy.
1
1
Thyroid
Thyroid ultrasound
Colorectal
Colonoscopy
Renal
Consider renal ultrasound
Melanoma
Currently there are no specific medical
management guidelines for melanoma risk
in mutation carriers other than tailored
dermatologic management as indicated by
1
skin findings.
Individualized
NA
Other - Nonmalignant
features of PHTS
Comprehensive physical examination.
Dermatologic management may be
indicated for some patients. Consider
psychomotor assessment in children and
1
brain MRI if there are symptoms.
18 years or earlier if
symptoms are present
Annually
1
Information for Family Members
3
FREQUENCY
1
The following information for Family Members will appear as part of the MMT for a patient found to have a mutation
in the PTEN 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.
This patient's relatives are also at risk for the complications associated with Cowden Syndrome (CS), Bannayan-RileyRuvalcaba Syndrome (BRRS), PTEN-related Proteus syndrome and Proteus-like Syndrome, some of which may
require medical attention in infancy or childhood.
References
1. 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.
2. Eng C. PTEN Hamartoma Tumor Syndrome (PHTS). 2016 June 2. In: Pagon RA, et al., editors. GeneReviews®
[Internet]. Available from http://www.ncbi.nlm.nih.gov/books/NBK1488/ PMID: 20301661.
3. Pilarski R. Cowden syndrome: a critical review of the clinical literature. J Genet Couns. 2009 18:13-27. PMID:
18972196.
4. Ngeow J, et al. Second Malignant Neoplasms in Patients With Cowden Syndrome With Underlying Germline
PTEN Mutations. J Clin Oncol. 2014 32:1818-24. PMID: 24778394.
5. Surveillance Research Program, National Cancer Institute SEER*Stat software (seer.cancer.gov/seerstat) V
8.0.1, Nov 19, 2012.
6. Riegert-Johnson DL, et al. Cancer and Lhermitte-Duclos disease are common in Cowden syndrome patients.
Hered Cancer Clin Pract. 2010 8:6. PMID: 20565722.
7. Bubien V, et al. High cumulative risks of cancer in patients with PTEN hamartoma tumour syndrome. J Med
Genet. 2013 50:255-63. PMID: 23335809.
8. Tan MH, et al. Lifetime cancer risks in individuals with germline PTEN mutations. Clin Cancer Res. 2012 18:4007. PMID: 22252256.
Last Updated on 10-Jan-2017
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