- 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)
PTEN Hamartoma Tumor Syndrome (PHTS) PTEN ASSOCIATED CANCER RISKS
PTEN Hamartoma Tumor Syndrome (PHTS)
PTEN ASSOCIATED CANCER RISKS
What does it mean to have a PTEN gene mutation, and a diagnosis of PTEN Hamartoma Tumor Syndrome (PHTS)?
People with mutations in the PTEN gene have a condition called PTEN Hamartoma Tumor Syndrome, or PHTS. In the past, people with PTEN mutations were sometimes given other diagnoses, depending on their individual symptoms. Examples include the diagnoses of Cowden Syndrome (CS), Bannayan-Riley-Ruvalcaba Syndrome (BRRS), PTEN-related Proteus Syndrome or Proteus-like Syndrome. We now know that all of these conditions are caused by mutations in the PTEN gene.
People with PHTS have a high risk for female breast, endometrial, colorectal, melanoma, kidney, and thyroid cancers.
People with PHTS often have other symptoms that are not cancers. There are a wide variety of symptoms that vary greatly from person to person. One of the most common is a larger than average head size. The technical name for this is macrocephaly. People with macrocephaly may have trouble finding hats or glasses that fit. Other symptoms that are sometimes noticed in patients with PHTS include fibrocystic breast disease, endometrial fibroids, and thyroid abnormalities. Sometimes people with PHTS have benign (non-cancerous) tumors in the brain known as Lhermitte-Duclos disease and/or distinctive types of moles and other skin conditions, such as trichilemmomas, acral keratoses and papillomatous papules. Developmental delay and autism have also been diagnosed in some children with PHTS.
What can be done to protect people with PHTS from cancer and other health problems?
The National Comprehensive Cancer Network (NCCN) provides recommendations for lowering the risk of cancer in men and women with PHTS. These recommendations include starting screening at younger ages than normal and having screenings more often. For example, yearly breast cancer screening with mammograms and/or MRIs should begin no later than age 35. Colonoscopies to check for colon cancer should begin at age 35 or younger, and should be done every 5 years. People with PHTS should also have special screenings that are not usually part of medical care for the general population. Examples include ultrasounds to screen for thyroid and kidney cancers.
Since PHTS can cause a variety of other health concerns, children and adults who are known to have PTEN mutations should have a careful and full evaluation to see if there are any problems that need to be addressed. A brain MRI might be recommended if there are signs of developmental delay or other neurological problems.
Because PHTS is a complicated condition that can affect many aspects of a person’s health, it is recommended that people with mutations in the PTEN gene be cared for by healthcare professionals with experience treating this condition. A list of centers that have specialized knowledge and experience with PHTS is available within our Support Organizations pages.
Additional details about PTEN gene mutations and PHTS, specific recommendations for medical care, and useful information for relatives of people who have a diagnosis of PHTS, are available at _____________________________.
Associated Syndrome Name: PTEN Hamartoma Tumor Syndrome (PHTS)
PTEN Summary Cancer Risk Table
|Cancer||Genetic Cancer Risk|
|Female Breast||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 PHTS-associated 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.
PTEN gene Cancer Risk Table
|Cancer Type||Age Range||Cancer Risk||Risk for General Population|
|Overall Cancer Risk (male and female)||To age 706, 7||85%-89%||20.9%|
|Female Breast||To age 701, 6, 7, 8||77%-85%||7.1%|
|Endometrial||To age 701, 6, 8||19%-28%||1.7%|
|Thyroid||To age 701, 6, 7, 8||21%-38%||0.9%|
|Colorectal||To age 701, 6, 8||9%-16%||1.8%|
|Renal||To age 701, 6, 8||15%-34%||0.8%|
|Melanoma||To age 701, 7, 8||Up to 6%||1.1%|
|Other - Non-malignant features of PHTS||All ages1, 2, 3||As described in the Overview above, PHTS is associated with non-malignant 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||Procedure||Age to Begin||Frequency |
(Unless otherwise indicated by findings)
|Overall Cancer Risk||Comprehensive physical examination and general education about the signs and symptoms of cancer, with particular attention to thyroid cancer.1||18 years or 5 years before the youngest age of a PHTS-related cancer in family||Annually|
|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.1||18 years||NA|
|Clinical breast examination1||25 years, or 5 to 10 years younger than the earliest diagnosis in the family, whichever comes first.||Every 6 to 12 months|
|Mammography with consideration of tomosynthesis and breast MRI with contrast1||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.1||Individualized||NA|
|Endometrial||Patient education about the importance of quickly seeking attention for endometrial cancer symptoms, such as abnormal bleeding or menstrual cycle irregularities1||Individualized||NA|
|Consider endometrial sampling and transvaginal ultrasound.1||Individualized for sampling. Transvaginal ultrasound should begin only after menopause||Every 1 to 2 years|
|Consider hysterectomy.1||After completion of childbearing||NA|
|Thyroid||Thyroid ultrasound1||At time of PHTS diagnosis||Annually|
|Colorectal||Colonoscopy1||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|
|Renal||Consider renal ultrasound1||40 years||Every 1 to 2 years|
|Melanoma||Currently there are no specific medical management guidelines for melanoma risk in mutation carriers other than tailored dermatologic management as indicated by skin findings.1||Individualized||NA|
|Other - Non-malignant features of PHTS||Comprehensive physical examination. Dermatologic management may be indicated for some patients. Consider psychomotor assessment in children and brain MRI if there are symptoms.1||18 years or earlier if symptoms are present||Annually|
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 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-Riley-Ruvalcaba Syndrome (BRRS), PTEN-related Proteus syndrome and Proteus-like Syndrome, some of which may require medical attention in infancy or childhood.
Parents who are concerned about the possibility of passing on a PTEN mutation to a future child may want to discuss options for prenatal testing and assisted reproduction techniques, such as pre-implantation genetic diagnosis (PGD).1
- 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.
- 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.
- Pilarski R. Cowden syndrome: a critical review of the clinical literature. J Genet Couns. 2009 18:13-27. PMID: 18972196.
- 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.
- 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)
- 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.
- 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.
- Tan MH, et al. Lifetime cancer risks in individuals with germline PTEN mutations. Clin Cancer Res. 2012 18:400-7. PMID: 22252256.
Last Updated on 07-Nov-2018