ArticleBreast cancer research and treatment2022
PTEN promoter methylation predicts 10-year prognosis in hormone receptor-positive early breast cancer patients who received adjuvant tamoxifen endocrine therapy.
Article in Breast cancer research and treatment, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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9 citing papers in PubMed, 15 citations in OpenAlex.
- Targeting epigenetic regulators as a promising avenue to overcome cancer therapy resistance.Signal transduction and targeted therapy · 2025Review
- PTEN-mediated resistance in cancer: From foundation to future therapies.Toxicology reports · 2025Review
- Decoding the Epigenome of Breast Cancer.International journal of molecular sciences · 2025Review
- PTEN and HES1 Gene Expression Alteration in Breast Cancer: Any Association with Tumor Histomorphological Features or Invasive Behavior?Asian Pacific journal of cancer prevention : APJCP · 2025Article
- DNA Methylation-Based Diagnosis and Treatment of Breast Cancer.Current cancer drug targets · 2025Review
- Crosstalk of methylation and tamoxifen in breast cancer (Review).Molecular medicine reports · 2024Review
- Characteristics of DNA macro-alterations in breast cancer with liver metastasis before treatment.BMC genomics · 2023Article
- A prospective cohort study of clinical characteristics and outcomes in Chinese patients with estrogen receptor-negative/progesterone receptor-positive early breast cancer.Breast cancer research and treatment · 2023Article
- A nomogram based on cuproptosis-related genes predicts 7-year relapse-free survival in patients with estrogen receptor-positive early breast cancer.Frontiers in oncology · 2023Article
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7 authors at 1 institution in 1 country.
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Abstract
purposeThere remain a lack of biomarkers for endocrine therapy resistance in patients with breast cancer (BC), which is proving to be a great challenge. In vitro experiments have shown that downregulation of PTEN expression leads to resistance to tamoxifen (TAM) in BC cells. We aimed to investigate the predictive role of tumor PTEN promoter methylation and PTEN expression in long-term survival after TAM adjuvant therapy in patients with early-stage BC.
methodsFrom 2001 to 2013, 105 patients with stage I-III BC who were treated with standardized adjuvant TAM for 5 years or until relapse in West China Hospital (WCH) were enrolled in this study. PTEN expression and DNA methylation of three specified sequences from the PTEN promoter in primary tumors were measured using immunohistochemistry and pyrosequencing. A cohort of 159 hormone receptor-positive patients receiving TAM treatment from The Cancer Genome Atlas (TCGA) database was used for verification.
resultsMedian follow-up time for the WCH cohort was 141.7 months. The low, moderate, and high PTEN expression groups had differing 10-year disease-free survival (DFS) (42.3%, 55%, 81%, respectively, P = 0.027) and overall survival (OS) rates (65%, 84.2%, 90.5%, respectively, P = 0.027). Higher methylation levels of the second sequence (- 819 to - 787 bp), rather than the first (- 1143 to - 1107 bp) or third sequence (- 663 to - 593 bp), independently increased the risk of disease recurrence (hazard ratio = 2.60) and death (hazard ratio = 3.79) in the WCH cohort, according to multivariate Cox regression analysis. Importantly, out of the five CpG islands located within this sequence, only high methylation of the - 796 CpG island predicted shorter DFS and OS. In TCGA validation cohort, there was also a trend of higher methylation of the - 796 CpG island correlating with shorter disease-free intervals, with borderline significance (P = 0.057).
conclusionLow PTEN expression and high methylation of its promoter (sequence - 819 to - 787 bp) in tissue predict poor DFS and OS in hormone receptor-positive early BC patients who received adjuvant TAM.
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