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.

Clinical Features of Li-Fraumeni Syndrome in Korea

“…Breast cancer showed early onset with a median age of 32-34 years, and in immunohistochemistry staining, the proportion of receptor expression was similar with 84%-90.5% ER positivity, 39.5%-63% HER2 positivity, and 32.8%-53% ER and HER2 co-expression. However, a Korean study by Alyami et al [ 10 ] showed differences in histological features and treatment outcomes. This study reported a lower rate of ER expression and a higher rate of triple-negative breast cancer.…”

“…Park et al [9] investigated the mutations and tumor spectra of LFS in Korean patients and identified two novel frameshift mutations in codons 98 and 27. Other studies on Korean patients have reported other types of mutation, such as frameshift or silent mutation (S2 Table) [9][10][11][12][13][14][15][16][17][18]. Based on the IARC database, the most common hotspot mutations were found in codons 175, 245, 248, 273, and 282 (http://p53.iarc.fr/).…”

“…In Korea, studies have analyzed 14 patients with nine different types of TP53 mutations [9] and 12 patients with LFS with breast cancer [10]. Other case reports also have described patients with LFS with various types of malignancies [11][12][13].…”

Case 10: A 30-Year-Old Woman With Breast Mass and Family History of Cancer

“… 14 Another retrospective study evaluated 21 breast cancer patients with LFS from South Korea and reported that around 50% of patients were HER2 positive, and 42% were ER or PR positive. 15 Considering around 20% of all breast cancers are HER2-positive, LFS breast cancer seems to be associated with HER2-positivity. Breast cancers in LFS also tend to have high tumor grade and similar morphologic features to somatic TP53 mutated breast cancers.…”

Risk of ipsilateral breast tumor recurrence and contralateral breast cancer in patients with and without TP53 variant in a large series of breast cancer patients

“…A recent study suggested that TP53 variant carriers exhibits a very high risk of contralateral breast cancer [23]. On the other hand, several studies with a limited sample size reported an increased risk of ipsilateral breast tumor recurrence in TP53 variant carriers who had a LFS or LFL syndrome [24][25][26]. Therefore, the risk of ipsilateral breast tumor recurrence and contralateral breast cancer should be taken into consideration when TP53 variant carriers received a surgical therapy.…”