{Reference Type}: Journal Article
{Title}: Case series of Li-Fraumeni syndrome: carcinogenic mechanisms in breast cancer with TP53 pathogenic variant carriers.
{Author}: Hosonaga M;Habano E;Arakawa H;Kaneko K;Nakajima T;Hayashi N;Fukada I;Nakamura A;Haruyama Y;Maeda T;Inari H;Kobayashi T;Nakashima E;Ueno T;Takano T;Takahashi S;Ohno S;Ueki A;
{Journal}: Breast Cancer
{Volume}: 31
{Issue}: 5
{Year}: 2024 Sep 17
{Factor}: 3.307
{DOI}: 10.1007/s12282-024-01612-3
{Abstract}: 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.