Xie Yuxin, Gou Qiheng, Wang Qianqian, Zhong Xiaorong, Zheng Hong
Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China.
Oncotarget. 2017 Aug 3;8(50):87151-87162. doi: 10.18632/oncotarget.19895. eCollection 2017 Oct 20.
Studies have showed that dysfunction in the breast cancer susceptibility gene (BRCA) is associated with triple-negative breast cancer (TNBC); however, its effect on patient survival remains controversial. We investigated the distribution of BRCA1/2 mutations in unselected Chinese patients with TNBC and explored their roles in prognosis. Then a systematic review and meta-analysis were performed to evaluate the prognostic role of BRCA dysfunction, including BRCA1/2 germline/somatic mutations, BRCA1 promoter methylation, and low BRCA1 protein expression in TNBC patients. Pooled hazard ratios with 95% confidence intervals were estimated to determine the association between BRCA dysfunction and survival. Our results showed a high frequency of BRCA1/2 mutations, especially germline BRCA1 variants, were associated with bilateral breast cancer. Although no correlations were found between BRCA1/2 mutations and recurrence-free survival (RFS) or overall survival (OS). In the meta-analysis, patients with BRCA1 promoter methylation showed poor OS. However, there was a favorable impact on disease free survival (DFS) for TNBC patients with BRCA1 promoter methylation when received adjuvant-chemotherapy. In conclusion, BRCA1/2 mutations were associated with bilateral breast cancer and BRCA1 promoter methylation may have a prognostic effect on TNBC.
研究表明,乳腺癌易感基因(BRCA)功能障碍与三阴性乳腺癌(TNBC)相关;然而,其对患者生存的影响仍存在争议。我们调查了未经选择的中国TNBC患者中BRCA1/2突变的分布情况,并探讨了它们在预后中的作用。然后进行了一项系统评价和荟萃分析,以评估BRCA功能障碍(包括BRCA1/2种系/体细胞突变、BRCA1启动子甲基化以及TNBC患者中BRCA1蛋白低表达)的预后作用。估计合并风险比及95%置信区间,以确定BRCA功能障碍与生存之间的关联。我们的结果显示,BRCA1/2突变频率较高,尤其是种系BRCA1变异,与双侧乳腺癌相关。尽管未发现BRCA1/2突变与无复发生存期(RFS)或总生存期(OS)之间存在相关性。在荟萃分析中,BRCA1启动子甲基化的患者总生存期较差。然而,接受辅助化疗时,BRCA1启动子甲基化的TNBC患者无病生存期(DFS)有良好影响。总之,BRCA1/2突变与双侧乳腺癌相关,BRCA1启动子甲基化可能对TNBC有预后影响。