背景:Li-Fraumeni综合征(LFS),归因于TP53致病变异的遗传性疾病,(PV),与各种恶性肿瘤的高风险有关,包括乳腺癌.值得注意的是,携带TP53PV的个体比非携带者(16-25%)更有可能(67-83%)发生HER2+乳腺癌.在这项回顾性研究中,我们评估了TP53变异与乳腺癌表型之间的关联.
方法:我们对在单一机构接受治疗的LFS患者的医疗记录进行了回顾性回顾,并回顾了TP53功能和LFS中HER2+乳腺癌发生的潜在机制的文献。
结果:我们分析了来自8个家庭的10例LFS患者的数据。第一次肿瘤发作时的中位年龄为35.5岁。只有案例2符合经典标准;这个病人有一个废话变体,而其他患者携带错义变异。我们观察到10例患者中有9例发展为乳腺癌。免疫组织化学分析显示,LFS患者中40%的乳腺癌为HR-/HER2。HR-/HER2+肿瘤在乳腺癌发病时的中位年龄略小于HR+/HER2-肿瘤(31岁和35.5岁,分别)。
结论:在我们的LFS病例系列中,HER2+乳腺癌亚型的发生率为40%,高于普通人群(16-25%)。一些TP53PV可能促进乳腺癌中HER2衍生的肿瘤发生。然而,有必要进行更大样本量的进一步研究,以阐明TP53PV携带者中各亚型乳腺癌的致癌机制.
BACKGROUND: Li-Fraumeni syndrome (LFS), a hereditary condition attributed to TP53 pathogenic variants,(PV), is associated with high risks for various malignant tumors, including breast cancer. Notably, individuals harboring TP53 PVs are more likely (67-83%) to develop HER2 + breast cancer than noncarriers (16-25%). In this retrospective study, we evaluated the associations between TP53 variants and breast cancer phenotype.
METHODS: We conducted a retrospective review of the medical records of patients with LFS treated at a single institution and reviewed the literature on TP53 functions and the mechanisms underlying HER2 + breast cancer development in LFS.
RESULTS: We analyzed data for 10 patients with LFS from 8 families. The median age at the onset of the first tumor was 35.5 years. Only case 2 met the classic criteria; this patient harbored a nonsense variant, whereas the other patients carried missense variants. We observed that 9 of 10 patients developed breast cancer. Immunohistochemical analyses revealed that 40% of breast cancers in patients with LFS were HR - /HER2 + . The median age at the onset of breast cancer was slightly younger in HR - /HER2 + tumors than in HR + /HER2 - tumors (31 years and 35.5 years, respectively).
CONCLUSIONS: The occurrence of HER2 + breast cancer subtype was 40% in our LFS case series, which is greater than that in the general population (16-25%). Some TP53 PVs may facilitate HER2-derived oncogenesis in breast cancer. However, further studies with larger sample sizes are warranted to clarify the oncogenic mechanisms underlying each subtype of breast cancer in TP53 PV carriers.