约有10%的乳腺癌与患者继承了乳腺癌易感基因中的一种致病变异体（PV）相关。包括TP53在内的多个乳腺癌易感基因会导致乳腺癌的风险增加。肿瘤蛋白-53（TP53）的生殖系 PVs 与 Li-Fraumeni综合征相关，这是一种罕见的常染色体显性遗传癌症易感综合征，与早期儿童肿瘤和多发性原发癌症（如软组织和骨肉瘤、乳腺癌、脑肿瘤、肾上腺皮质癌和白血病）有关。携带 TP53 PV 的女性发生乳腺癌的终生风险为 80-90%。本综述的目的是对提供 TP53 测定标准、患者中 TP53 携带者的患病率以及已知的预后和治疗影响进行全面概述。此外，还提供了当前二次癌症监测和康复问题的摘要。最后，讨论了 TP53 变化和测试的范围。治疗携带 TP53 PV 的乳腺癌患者的最佳策略面临一定挑战。当前的指南倾向于执行乳房切除术，而不是乳腺切除术，以避免辅助放疗及其后续放射性二次原发恶性肿瘤的风险，并在必要时谨慎考虑放射线治疗后。一些研究表明，乳腺癌和生殖系 TP53 PV 患者与野生型 TP53状态的乳腺癌患者相比，可能有较差的生存结局。建议进行年度乳腺磁共振成像 （MRI）和全身MRI作为二级预防方法。版权所有© 2023 The Authors. Published by Elsevier Ltd.。保留所有权利。

Approximately 10% of breast cancers are associated with the inheritance of a pathogenic variant (PV) in one of the breast cancer susceptibility genes. Multiple breast cancer predisposing genes, including TP53, are responsible for the increased breast cancer risk. Tumor protein-53 (TP53) germline PVs are associated with Li-Fraumeni syndrome, a rare autosomal dominant inherited cancer predisposition syndrome associated with early-onset pediatric and multiple primary cancers such as soft tissue and bone sarcomas, breast cancer, brain tumors, adrenocortical carcinomas and leukemias. Women harboring a TP53 PV carry a lifetime risk of developing breast cancer of 80-90%. The aim of the present narrative review is to provide a comprehensive overview of the criteria for offering TP53 testing, prevalence of TP53 carriers among patients with breast cancer, and what is known about its prognostic and therapeutic implications. A summary of the current indications of secondary cancer surveillance and survivorship issues are also provided. Finally, the spectrum of TP53 alteration and testing is discussed. The optimal strategies for the treatment of breast cancer in patients harboring TP53 PVs poses certain challenges. Current guidelines favor the option of performing mastectomy rather than lumpectomy to avoid adjuvant radiotherapy and subsequent risk of radiation-induced second primary malignancies, with careful consideration of radiation when indicated post-mastectomy. Some studies suggest that patients with breast cancer and germline TP53 PV might have worse survival outcomes compared to patients with breast cancer and wild type germline TP53 status. Annual breast magnetic resonance imaging (MRI) and whole-body MRI are recommended as secondary prevention.Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.