%0 Journal Article
%T Case series of Li-Fraumeni syndrome: carcinogenic mechanisms in breast cancer with TP53 pathogenic variant carriers.
%A Hosonaga M
%A Habano E
%A Arakawa H
%A Kaneko K
%A Nakajima T
%A Hayashi N
%A Fukada I
%A Nakamura A
%A Haruyama Y
%A Maeda T
%A Inari H
%A Kobayashi T
%A Nakashima E
%A Ueno T
%A Takano T
%A Takahashi S
%A Ohno S
%A Ueki A
%J Breast Cancer
%V 31
%N 5
%D 2024 Sep 17
%M 39017822
%F 3.307
%R 10.1007/s12282-024-01612-3
%X <B>BACKGROUND: </B>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.<BR><B>METHODS: </B>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.<BR><B>RESULTS: </B>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).<BR><B>CONCLUSIONS: </B>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.