There are limited data on the effectiveness of cancer screening specifically in germline TP53 mutation carriers. Data about the utility of breast cancer and bowel cancer screening are mostly extrapolated from cancer screening studies in other groups at increased risk of these cancers.
There is strong evidence that bilateral mastectomy significantly reduces breast cancer risk in high risk women.
There is limited data about the utility of breast MRI screening specifically in TP53 mutation carriers. In women with an increased risk of breast cancer due to a germline BRCA mutation, breast MRI has been shown to detect more tumours and at an earlier stage than mammogram alone.
Similarly, there is no published study evaluating potential detrimental effect of ionising radiation (mammography) used for screening purposes in TP53 mutation carriers. However, there is a concern about the cumulative risk of mammograms in very young women exposed to mammograms for a long period of timer and mammograms may be more difficult to interpret in younger women with denser breasts.
Risk reducing medication
Tamoxifen and raloxifene have been shown to reduce the risk of breast cancer in high risk women, although there is no specific data for TP53 mutation carriers. The lifetime breast cancer risk is sufficient to offer risk reducing medication according to Cancer Australia risk-reducing medication resource
Breast radiotherapy is associated with development of multiple new primary cancers of breast and adjacent local tissues in TP53 mutation carriers.rr Therefore radiation therapy should be avoided where possible and therapeutic mastectomy considered in preference and mammography avoided for screening if breast MRI is available.
Colorectal and gastric cancers
There is limited evidence about the effectiveness of gastrointestinal screening in TP53 mutation carriers. The early age of onset (median 40 years, range: females 21-74 years; males 27-52 years)r of bowel cancers in some families may justify regular colonoscopy screening, which has been shown to significantly reduce bowel cancer risk in families at moderate-high risk.
The risk of cancer varies significantly by age and gender:r
See table Number and type of first cancer by age group at the time of diagnosis.r
At present there is insufficient evidence for (or against) routine screening for the core cancers in LFS apart from breast cancer and bowel cancer.
A recent prospective study of biochemical and imaging surveillance, including whole-body and brain MRI, in germline TP53 mutation carriers (both children and adults), showed that a comprehensive surveillance protocol is feasible, and that early tumour detection through surveillance is associated with improved survival: 5-year overall survival of 88.8% (95%CI, 78.7-100) in the surveillance group vs 59.6% (47.2-75.2) in the non-surveillance group (p=0.0132).r False-positive rate associated with imaging surveillance in this study was <5%. Only biopsies that were pathologically non-neoplastic were considered as false-positives, and the number of follow-up investigations prompted by imaging results was not reported.
Several other centres worldwide are currently evaluating screening protocols using whole-body MRI.rr Further data are needed to show consistent survival benefit, before a comprehensive screening protocol can be recommended routinely in the management of families with TP53 mutations.
TP53 mutations are believed to cause radiation sensitivity, due to impaired recognition and repair of DNA damage and there are numerous reports of second primary malignancies developing in areas previously treated with radiation therapy. Minimising radiation therapy is recommended where possible, especially if other treatment modalities with comparable cure rates are available. Similarly tests using ionising radiation should be avoided if other effective modalities are available.r
There is evidence that smoking increases the risk of lung cancers in TP53 mutation carriers by 3 fold.r