Breast cancer
Surgical
There are no studies on risk-reducing mastectomy in women with a PTEN pathogenic variant but bilateral risk-reducing mastectomy has been shown to reduce cancer risk in women with pathogenic variants in BRCA1/2 by at least 90% (depending on the operation performed).rr
Statistically significant survival benefit associated with bilateral risk-reducing mastectomy compared with surveillance is yet to be demonstrated.
Surveillance
MRI is the preferred screening technique due to its high sensitivity compared with MMG or US. The addition of MMG is limited and does not lead to a significant increase in sensitivity compared with MRI alone.r There is no added value of ultrasound in women undergoing MRI for screening. MRI detects tumours which are smaller and more likely to be node-negative than MMG. MRI has a recall rate (requiring further investigation and/or biopsy) of 15% for initial screening, which decreases with subsequent rounds of screening to <10%.
Mammography screening is not recommended before age 40 years in PTEN pathogenic variant carriers. The sensitivity of MRI is not influenced by age or breast density, being similar in women aged >50 years to those aged <50 years. On current evidence, it may be reasonable to offer breast MRI to women with PTEN pathogenic variants beyond age 50 years.
There is no evidence to date that early detection of breast cancer is associated with a better prognosis and survival in PTEN gene pathogenic variant carriers. However, for women who do not choose risk-reducing surgery, surveillance is strongly recommended.
Risk-reducing medication
There are no studies on risk-reducing medication in patients with a PTEN pathogenic variant. This needs to be considered on a case-by-case basis due to the risk of endometrial cancer in this condition.
Endometrial cancer
Surgical
Hysterectomy is the only proven intervention which significantly reduces the risk of endometrial cancer.r
Surveillance
There is no evidence to support a survival benefit from TVU and aspiration biopsy. Where possible, surveillance should be offered in the context of a clinical trial.r
Thyroid cancer
There are a number of international guidelines which include a recommendation for surveillance with thyroid US in patients with a PTEN pathogenic variant. However, there are no published studies demonstrating that ultrasonography is likely to detect malignant abnormalities that would not have been found on clinical examination, nor that it would result in improved outcomes following a diagnosis of thyroid cancer.
Renal cancer
Some groups suggest second-yearly renal US from age 40 years.r There is no evidence for or against this investigation, although there is strong evidence that identification of early stage RCCs in other populations leads to significantly better outcomes. There have been no studies investigating which modality should be used for surveillance.
Colorectal cancer
Some patients develop adenomas and hyperplastic polyps in addition to colonic hamartomas. Whilst an increased risk of young onset colorectal cancer (9%) has been reported,r there is limited evidence that all families with PTEN are at high risk of bowel cancer. Families with a history of colorectal cancer should follow screening guidelines based on their family history of colorectal cancer and consider a low threshold for investigation if symptomatic.
Evidence regarding other cancers
Summaries of PTEN pathogenic variant carriers also report an increased risk of melanoma,r although the absolute risk is still thought to be small.