PROGNOSTIC SIGNIFICANCE OF TR53 GENE MUTATION IN PATIENTS WITH METASTATIC HER2-POSITIVE BREAST CANCER
Authors: Vynnychenko O. I. , Moskalenko Y. V. , Denysenko A. P. , Moskalenko R. A. 
Published: January 2025

The p53 protein participates in many cellular processes, including DNA repair, cell cycle control, autophagy, apoptosis, and senescence. Мutation in the TP53 gene is a factor of unfavorable prognosis. Loss of tumor suppressor function causes resistance to drug therapy, metastasis, and disease progression. However, breast cancer is a heterogeneous disease with unique and, at first glance, paradoxical biological mechanisms for each subtype. Several studies have shown that a mutation in the TP53 gene predicts the effectiveness of trastuzumab therapy and chemotherapy. The assessment of TR53 status may influence the treatment choice.
The aim of our study was to investigate the prognostic significance of the TP53 gene mutation in patients with metastatic human epidermal growth factor receptor 2 (HER2)-positive breast cancer.
Materials and methods. Seventy-eight patients of the Sumy Regional Clinical Oncology Center were involved in the study. The criteria for inclusion in the study were a history of trastuzumab monotherapy or combined chemotherapy and trastuzumab, age 18 years and older. The exclusion criteria were the presence of another malignant tumor, infectious, autoimmune, or inflammatory diseases before the start of trastuzumab therapy and the absence of trastuzumab in the used therapeutic scheme. Immunohistochemistry with antibodies against the p53 protein was used to determine the status of the TR53 gene. Pearson test, Kaplan-Meier method, Log-rank test, and Cox regression were used for statistical analysis.
The results. 64.1% of patients with metastatic HER2-positive breast cancer have a TP53 gene mutation. Patients with a mutant type of TP53 more often received a combination of trastuzumab and chemotherapy (χ2=6.9348, p=0.008). In patients with wild-type TP53, hormone-positive HER2-positive breast cancer was predominant (χ2=5.0547, p=0.005). At the end of the follow-up period, death was recorded in 69/78 (88.5%) patients, including 26/28 (92.9%) patients with wild-type TP53 and 43/50 (86.0%) patients with mutant TP53. In patients with wild-type TP53, median survival was 13.6 months and 21.0 months for trastuzumab monotherapy and the combination of trastuzumab with chemotherapy, respectively (Log-rank p=0.9500). In patients with mutant TP53, median survival was 22.4 months and 36.6 months for trastuzumab monotherapy and the combination of trastuzumab with chemotherapy, respectively (Log-rank p=0.0063). In patients with wild-type TP53, median survival was 21.6 months and 13.0 months for hormone-positive and hormone-negative, respectively (Log-rank p=0.0095). In patients with mutant TP53, median survival was 34.2 months and 31.2 months for hormone-positive and hormone-negative, respectively (Log-rank p=0.3509). Hormonal status, the applied treatment regimen, and the status of the TR53 gene were determined as independent predictors of overall survival.
Conclusions. Among patients with wild-type TP53, hormone-positive breast cancer predominates, but patients with mutant TP53, especially those with negative hormone status, have better survival. Patients with mutant TP53 who receive a combination of trastuzumab and chemotherapy have better overall survival than those who receive trastuzumab monotherapy. Hormone-positive breast cancer, combination of trastuzumab and chemotherapy, and mutation in the TP53 gene are independent predictors of better overall survival in patients with metastatic HER2-positive breast cancer.