Dataset Information

Clinical Features of Breast Cancer in South Korean Patients with Germline TP53 Gene Mutations.

ABSTRACT:

Purpose

Li-Fraumeni syndrome (LFS) is a rare autosomal cancer syndrome caused by a germline mutation in the TP53 gene. Breast cancer in LFS patients is of various subtypes; however, limited data are available on the clinicopathological features of these subtypes and their appropriate treatments. This study aimed to review the clinical features and treatments for breast cancer in South Korean patients with germline TP53 mutations.

Methods

Data on the clinicopathological features and treatment of all breast cancer patients with LFS were collected retrospectively from the available database of 4 tertiary hospitals in the Republic of Korea.

Results

Twenty-one breast cancer cases in 12 unrelated women with confirmed germline TP53 mutations were included in the study. The median age at diagnosis was 33.5 years. The histopathological diagnosis included invasive ductal carcinoma (n = 16), ductal carcinoma in situ (n = 3), and malignant phyllodes tumor (n = 2). While 42% and 31% of the cases were positive for estrogen and progesterone receptors, respectively, 52.6% were human epidermal growth factor receptor 2 (HER2) positive, and 21% were triple-negative. The treatments included mastectomy (52%) and breast-conserving surgery (38%). Five patients underwent radiotherapy (RT). The median follow-up period was 87.5 (8-222) months. There were 3 ipsilateral and 4 contralateral breast recurrences during the follow-up, and 8 patients developed new primary cancers. In the post-RT subgroup, there were 2 ipsilateral and 2 contralateral breast recurrences in 1 patient, and 4 patients had a new primary cancer.

Conclusion

As reported in other countries, breast cancer in LFS patients in South Korea had an early onset and were predominantly but not exclusively positive for HER2. A multidisciplinary approach with adherence to the treatment guidelines, considering mastectomy, and avoiding RT is encouraged to prevent RT-associated sequelae in LFS patients.

SUBMITTER: Alyami H

PROVIDER: S-EPMC8090805 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundHeterozygous germline TP53 gene mutations result in Li-Fraumeni Syndrome (LFS). Breast cancer (BC) is the most frequent tumor in young women with LFS. An important issue related to BC in the Mexican population is the average age at diagnosis, which is approximately 11 years younger than that of patients in the United States (U.S.) and Europe. The aim of this study was to determine the prevalence of germline mutations in TP53 among young Mexican BC patients.MethodsWe searched for germline mutations in the TP53 gene using targeted next-generation sequencing (NGS) in 78 BC patients younger than 45 years old (yo) who tested negative for BRCA1/2 mutations. A group of 509 Mexican women aged 45yo or older without personal or family BC history (parents/grandparents) was used as a control.ResultsWe identified five patients with pathogenic variants in the TP53 gene, equivalent to 6.4% (5/78). Among patients diagnosed at age 36 or younger, 9.4% (5/55) had pathogenic TP53 mutations. Three of these variants were missense mutations (c.844C > T, c.517G > A, and c.604C > T), and the other two mutations were frameshifts (c.291delC and c.273dupC) and had not been reported previously. We also identified a variant of uncertain clinical significance (VUS), c.672G > A, which causes a putative splice donor site mutation. All patients with TP53 mutations had high-grade and HER2-positive tumors. None of the 509 patients in the healthy control group had mutations in TP53.ConclusionsAmong Mexican BC patients diagnosed at a young age, we identified a high proportion with germline mutations in the TP53 gene. All patients with the TP53 mutations had a family history suggestive of LFS. To establish the clinical significance of the VUS found, additional studies are needed. Pathogenic variants of TP53 may explain a substantial fraction of BC in young women in the Mexican population. Importantly, none of these mutations or other pathological variants in TP53 were found in the healthy control group.