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TP53 mutations and SNPs as prognostic and predictive factors in patients with breast cancer.

ABSTRACT: Tumor protein 53 (TP53) is a tumor suppressor gene that encodes tumor protein p53. Tumor protein p53 regulates the expression of target genes in response to cellular stress. Additionally, p53 participates in the regulation of cell cycle checkpoints, DNA repair and apoptosis. Mutations in the TP53 gene are associated with numerous types of human cancer, including breast cancer, sarcomas, brain tumors and adrenal cortical carcinomas. In breast cancer, TP53 mutations are a negative prognostic factor. Tumors with TP53 mutations are more likely to be aggressive (triple-negative or human epidermal growth factor receptor 2-positive breast cancer), and resistant to chemotherapy and radiotherapy. In addition to a well-known TP53 mutation, a number of single nucleotide polymorphisms have been systematically identified and evaluated in human populations. In the present article, the role of TP53 mutations and polymorphisms in clinical practice and breast cancer treatment has been described. Additionally, the existing data on TP53 polymorphisms in breast cancer as prognostic and predictive factors have been summarized. A literature search of these topics was performed through PubMed and abstracts of the main cancer congresses in recent years.

SUBMITTER: Huszno J

PROVIDER: S-EPMC6006469 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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TP53 mutations and SNPs as prognostic and predictive factors in patients with breast cancer.

Huszno Joanna J Grzybowska Ewa E

Oncology letters 20180503 1

Tumor protein 53 (TP53) is a tumor suppressor gene that encodes tumor protein p53. Tumor protein p53 regulates the expression of target genes in response to cellular stress. Additionally, p53 participates in the regulation of cell cycle checkpoints, DNA repair and apoptosis. Mutations in the TP53 gene are associated with numerous types of human cancer, including breast cancer, sarcomas, brain tumors and adrenal cortical carcinomas. In breast cancer, TP53 mutations are a nega ...[more]

PMID: 29928384

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Project description:BACKGROUND:TP53 mutations are common in breast cancer. There is currently no large-scale cohort study to investigate the TP53 landscape in breast cancer patients from China. The predictive value of TP53 mutations for the efficacy of human epidermal growth factor receptor 2 (HER2)-targeted therapy in breast cancer remains controversial. In the present study, we aimed to analyze the clinical spectrum and prognostic value of TP53 mutations in circulating tumor DNA (ctDNA) from breast cancer patients in China. METHODS:We retrospectively analyzed the clinical data and TP53 mutation features in ctDNA samples from 804 patients with metastatic breast cancer. TP53 mutations were detected by target region capture-based next-generation sequencing. The relationship between TP53 mutation status and disease-free survival (DFS) was analyzed in 444 patients with metastatic breast cancer. Moreover, the relationship between TP53 mutation status and progression-free survival (PFS) was analyzed in 55 HER2-positive patients treated with first-line trastuzumab-based therapy. Kaplan-Meier analysis was performed to estimate the survival curves of the different subgroups, and the log-rank test was used to compare the curves. A Cox regression model was used to estimate multivariable-adjusted hazard ratios and their 95% confidence intervals (CIs) associated with the DFS and PFS. RESULTS:Among the 804 investigated patients, 431 (53.6%) patients harbored TP53 mutations. TP53 mutations were differentially distributed among different molecular subtypes of breast cancer (P < 0.05). Patients with TP53 mutations had a shorter DFS than those with wild-type TP53 (hazard ratio = 1.32, 95% CI = 1.09-1.61, P = 0.005). TP53 mutations in exons 5-8 were associated with worse outcome (hazard ratio = 1.50, 95% CI = 1.11-2.03, P = 0.009). However, TP53 mutation status was not significantly associated with PFS in HER2-positive patients who received first-line trastuzumab-based therapy (P = 0.966). Interestingly, in the taxane combination group, patients with TP53 mutations exhibited longer PFS than those without TP53 mutations (hazard ratio = 0.08, 95% CI = 0.02-0.30, P < 0.001). However, in the non-taxane combination group, patients with TP53 mutations displayed shorter PFS than those with wild-type TP53 (hazard ratio = 4.84, 95% CI = 1.60-14.66, P = 0.005). CONCLUSIONS:TP53 mutations in exons 5-8 may be an independent prognostic marker for short DFS in patients with metastatic breast cancer. TP53 mutations had opposite effects on trastuzumab-treated patients treated with and without taxanes.

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TP53 mutations and SNPs as prognostic and predictive factors in patients with breast cancer.

Publications

<i>TP53</i> mutations and SNPs as prognostic and predictive factors in patients with breast cancer.

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