Blondeaux Eva, Arecco Luca, Punie Kevin, Graffeo Rossella, Toss Angela, De Angelis Carmine, Trevisan Lucia, Buzzatti Giulia, Linn Sabine C, Dubsky Peter, Cruellas Mara, Partridge Ann H, Balmaña Judith, Paluch-Shimon Shani, Lambertini Matteo
Clinical Epidemiology Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy.
Department of Internal Medicine and Medical Specialties (DiMI), School of Medicine, University of Genova, Genoa, Italy; Department of Medical Oncology, U.O. Clinica di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, Genoa, Italy.
Cancer Treat Rev. 2023 Mar;114:102522. doi: 10.1016/j.ctrv.2023.102522. Epub 2023 Jan 31.
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.
大约10%的乳腺癌与乳腺癌易感基因之一的致病变异（PV）遗传有关。包括TP53在内的多个乳腺癌易感基因会导致乳腺癌风险增加。肿瘤蛋白53（TP53）种系PV与李-佛美尼综合征相关，这是一种罕见的常染色体显性遗传癌症易感综合征，与儿童期早发和多种原发性癌症有关，如软组织和骨肉瘤、乳腺癌、脑肿瘤、肾上腺皮质癌和白血病。携带TP53 PV的女性患乳腺癌的终生风险为80-90%。本叙述性综述的目的是全面概述提供TP53检测的标准、乳腺癌患者中TP53携带者的患病率，以及其预后和治疗意义的相关情况。还提供了继发性癌症监测和生存问题的当前指征总结。最后，讨论了TP53改变和检测的范围。治疗携带TP53 PV的乳腺癌患者的最佳策略面临一定挑战。当前指南倾向于选择乳房切除术而非肿块切除术，以避免辅助放疗及随后辐射诱发第二原发性恶性肿瘤的风险，乳房切除术后如有指征需谨慎考虑放疗。一些研究表明，与乳腺癌且种系TP53为野生型状态的患者相比，乳腺癌且种系TP53 PV的患者生存结果可能更差。建议每年进行乳腺磁共振成像（MRI）和全身MRI作为二级预防。
