Purpose: This review describes the prevalence of germline TP53 mutations, the risk of breast cancer and other cancers in mutation carriers and management implications for women with breast cancer and unaffected women.
Methods: Literature review of English language papers available through PubMed.
Results: Women who carry germline mutations in the TP53 gene have a very high risk of breast cancer of up to 85% by age 60 years. Most of these breast cancers are early onset with a median age at diagnosis of 34 years. Approximately 5-8% of women presenting with breast cancer under 30 years old have a germline TP53 gene mutation. Breast cancers in women with TP53 mutations are more likely to be hormone receptor positive and/or Her2 positive. Mastectomy is recommended over lumpectomy in TP53 mutation carriers who have breast cancer so that adjuvant breast radiotherapy can be avoided. Risk-reducing surgery should be considered due to the high contralateral breast cancer risk. Mutation carriers are at high risk of various childhood and adult-onset cancers with a very lifetime risk of malignancy, the commonest malignancies being breast cancer and soft tissue sarcoma. In unaffected female mutation carriers, MRI breast screening or risk-reducing surgery is recommended. The optimal surveillance for other cancers is currently unclear and should ideally be performed as part of a clinical trial.
Conclusions: Identifying a TP53 mutation in a gene panel test is a challenging result for the patient and clinician due to the high risk of second primaries and the lack of consensus about surveillance.
Keywords: Gene panel testing; Li–Fraumeni syndrome; TP53.