Bilateral risk-reducing mastectomy reduces absolute breast cancer risk to <2%.r
Statistically significant survival benefit associated with bilateral risk-reducing mastectomy compared with surveillance is yet to be demonstrated.
Previous studies have reported in BRCA1 or BRCA2 pathogenic variant carriers,r pre-menopausal risk reducing salpingo-oophorectomy (RRBSO) would be expected to reduce the risk of breast cancer. However, a recent prospective study has shown no reduction in the risk of breast cancer in BRCA1 or BRCA2 carriersr. No studies have been done in women with Cowden syndrome.
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 aloner. 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%.
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.
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.
Hysterectomy is the only proven intervention which significantly reduces the risk of endometrial cancer.r
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
Surveillance is not recommended because there have been no studies demonstrating benefit of screening thyroid ultrasound unless there are palpable nodules.r
Some groups suggest second yearly renal US from age 40 years.r However there is no evidence for or against this investigation.
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 no 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
A recent summary of PTEN pathogenic variant carriers also reported an increased risk of melanoma,r although the risk was still small.