Promoter methylation of BRCA1 is associated with estrogen, progesterone and human epidermal growth factor receptor-negative tumors and the prognosis of breast cancer: A meta-analysis

Abstract

Aberrant methylation of the breast cancer susceptibility gene 1 (<i>BRCA1</i>) promoter is a mechanism for its functional inactivation. It may potentially be used as a prognostic marker in studies for patients with breast cancer and plays an important role in tumorigenesis. Numerous studies have suggested that the methylation of the <i>BRCA1</i> promoter is associated with the prognosis of breast cancer. However, the prognosis of <i>BRCA1</i> promoter methylation in breast cancer patients of different ethnicities remains ambiguous. The present meta-analysis was performed to adjust and augment a previously published study, which estimated the correlations between promoter methylation of <i>BRCA1</i> and the clinical outcomes of breast cancer patients. These results indicated that <i>BRCA1</i> methylation was significantly correlated with a poor prognosis of breast cancer, particularly for Asian patients, but the correlation was over-estimated in the previous study. The combined hazard ratios (HRs) in the present study were 1.76 (1.15-2.68) and 1.97 (1.12-3.44) for univariate and multivariate analysis of overall survival, which were different from 2.02 (1.35-3.03) and 1.38 (1.04-1.84) in the previous study. For studies of disease-free survival, the univariate and multivariate analyses also have different pooled HRs: 2.89 (1.73-4.83) and 3.92 (1.49-10.32) in the previously published study and 1.28 (0.68-2.43) and 1.64 (0.64-4.19) in the present study. In addition, the <i>BRCA1</i> promoter regions used to detect the hypermethylation were different. All the studies using the Baldwin's primer reported that breast cancer patients with <i>BRCA1</i> promoter methylation had a better prognosis. There were also correlations between <i>BRCA1</i> promoter methylation and receptor-negativity of the estrogen receptors, progesterone receptor, human epidermal growth factor receptor 2 and a triple-negative status. Patients with the estrogen, progesterone and epidermal growth factor-related receptor-negative status were more likely to be negative for the BRCA1 protein.