Case series of Li-Fraumeni syndrome: carcinogenic mechanisms in breast cancer with TP53 pathogenic variant carriers

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2024年7月17日

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Mari Hosonaga,
Eri Habano,
Hiromi Arakawa,
Keika Kaneko,
Takeshi Nakajima,
Naomi Hayashi,
Ippei Fukada,
Akira Nakamura,
Yurie Haruyama,
Tetsuyo Maeda,
Hitoshi Inari,
Takayuki Kobayashi,
Eri Nakashima,
Takayuki Ueno,
Toshimi Takano,
Shunji Takahashi,
Shinji Ohno,
Arisa Ueki

摘要

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.